What changed in this filing

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Item 1. Business

2024-03-08 compared with 2023-03-13 · 3595 added, 3780 removed, 220 unchanged (97% of the section changed)

This section is long enough that the comparison stopped early. What follows is partial, and the remainder is not necessarily unchanged.

We are a clinical-stage, precision

medicine pharmaceutical company actively advancing a pipeline of in-licensed oncology therapeutics for patients with difficult-to-treat

Our clinical program includes three anti-cancer assets in mid-stage clinical development and one anti-cancer asset in early-stage

clinical development.

Our programs and partnerships leverage our proprietary, highly accurate Drug Response Predictor (DRP ® )

technology to refine patient selection and improve clinical outcomes.

Our DRP ® technology has been broadly validated across

an extensive array of therapies and tumor types with a high degree of accuracy for matching the right patient to the right drug.

is a clinical-stage, precision medicine pharmaceutical company actively advancing in-licensed oncology therapeutics for patients with

difficult-to-treat cancers leveraging Allarity’s core technology, the Drug Response Predictor (DRP ® ) platform, to

identify the patients most likely to derive clinical benefit from any individual therapeutic.

In Q4, 2023, Allarity made significant

changes to its business to align with current financial realities and to streamline the Allarity pipeline in order to focus resources

on the clinical asset with the highest likelihood to create near and mid-term value, stenoparib.

Other assets in the portfolio, namely

dovitinib and Ixempra, have been terminated or deprioritized, respectively.

Outlicensed assets, namely 2X-111, LiPlaCis and Irofulven,

are being developed exclusively by partners in a variety of indications at the partner’s discretion with support from Allarity

limited to the DRP ® technology for each asset.

Our DRP ® technology has been broadly validated across an

extensive array of therapies and tumor types with a high degree of accuracy for matching the right patient to the right drug.

By identifying

those patients who will and who will not respond, the DRP ® companion diagnostics have the potential to transform cancer

therapeutic development across many indications by increasing clinical success rates with trials involving a fewer number of patients

and improve patient outcomes by matching them to the right drug.

Our pipeline currently consists

of three mid-stage clinical candidates for cancer and one anti-cancer asset in early-stage clinical development.

We are focused on the

clinical development of three priority programs:

dovitinib in combination with stenoparib for the second-line or later treatment of metastatic

ovarian cancer, stenoparib as a monotherapy for ovarian cancer, and IXEMPRA ® as a monotherapy for metastatic breast cancer.

In addition, Allarity is supporting the development of one additional clinical asset through business development activities.

Each Allarity

pipeline program is being co-developed with a drug specific DRP ® companion diagnostic to select and treat patients most

likely to benefit from treatment.

While we have not yet successfully

received regulatory or marketing approval for any of our therapeutic candidates or companion diagnostics, and while we believe that our

approach has the potential to reduce the cost and time of drug development through the identification and selection of patient populations

more likely to respond to therapy, our strategy involves risks and uncertainties that differ from other biotechnology companies that focus

solely on new therapeutic candidates that do not have a history of failed clinical development.

By utilizing our DRP ® platform

to generate a drug-specific companion diagnostic for each of our therapeutic candidates, if approved by the FDA, we believe our therapeutic

candidates have the potential to advance the goal of personalized medicine by selecting the patients most likely to benefit from each

of our therapeutic candidates and avoid the treatment of non-responder patients.

All of our therapeutic candidates are clinical stage

assets and the FDA has not yet approved any of our therapeutic candidates or any of our DRP ® companion diagnostics.

used in this report, statements regarding the use of our proprietary DRP ® companion diagnostics or our proprietary DRP ®

platform or our observations that a therapeutic candidate may have anti-cancer or anti-tumor activity or is observed to be well tolerated

in a patient population should not be construed to mean that we have resolved all issues of safety and/or efficacy for any of our therapeutic

candidates or DRP ® companion diagnostic.

Issues of safety and efficacy for any therapeutic candidate or companion diagnostic

may only be determined by the U.S.

FDA or other applicable regulatory authorities in jurisdictions outside the United States.

Our clinical and commercial

development team is advancing our pipeline of targeted oncology therapeutic candidates, all of which have previously succeeded at least

through Phase 1 clinical trials demonstrating that the therapeutic candidate is well tolerated.

Our three priority assets, dovitinib,

stenoparib, and IXEMPRA ® (ixabepilone) are all former drug candidates of large pharmaceutical companies.

Our most advanced therapeutic

candidate, dovitinib, is a selective inhibitor of several classes of tyrosine kinases, including FGFR and VEGFR, and was formerly developed

by Novartis Pharmaceuticals through Phase 3 clinical trials in numerous indications.

We submitted an NDA with the FDA on December 21,

2021, for the third line treatment of metastatic renal cell carcinoma (mRCC or kidney cancer) in patients selected by our Dovitinib-DRP ®

companion diagnostic.

Prior to submission of the NDA, we submitted a Pre-Market Approval (PMA) application to the FDA for approval of

our dovitinib-specific DRP ® companion diagnostic for use to select and treat patients likely to respond to dovitinib.

February 15, 2022, we received Refusal to File (RTF) letters for both our dovitinib NDA and our DRP ® -Dovitinib companion

diagnostic PMA.

The FDA has asserted that neither our NDA or PMA meets the regulatory requirements to warrant a complete agency review.

The primary grounds of rejection asserted by the FDA relates to our use of prior Phase 3 clinical trial data, generated by Novartis in

a “superiority” endpoint study against sorafenib (Bayer), to support a “non-inferiority” endpoint and superiority

in connection with the DRP ® -Dovitinib companion diagnostic.

Based upon the reasons given in the RTF letters and a subsequent

Type C meeting with the FDA on May 31, 2022, we anticipate that the FDA will require a prospective Phase 3 clinical trial as well as additional

dose optimization studies before regulatory approval of Dovitinib as a monotherapy and its companion diagnostic Dovitinib-DRP for the

treatment of third-line mRCC can be obtained.

While we have decided that the costs, risks and potential benefits of conducting these studies

for dovitinib as a monotherapy for mRCC are no longer the best path toward commercial success, we continue to evaluate other potential

Phase 1b/2 clinical trials for dovitinib combined with other approved drugs in the mRCC space and in other indications.

For example, subject

to funding we anticipate commencing a stenoparib in combination with dovitinib Phase 1b/2 clinical trial for second-line or later treatment

of metastatic ovarian cancer and/or other solid tumors.

Our decision to advance dovitinib as a combination therapy and not as a monotherapy

is based on our belief that both the science and the market for oncology therapies has shifted towards combination therapies and away

from monotherapies for multiple indications of cancer.

We further believe that our DRP ® -Dovitinib companion diagnostic

is tumor agnostic and our retrospective analysis of the clinical data generated in the Novartis clinical studies for mRCC will also support

a companion diagnostic for dovitinib in second-line or later treatment of metastatic ovarian cancer, as well as other indications.

Our second priority therapeutic

candidate is stenoparib (formerly E7449), a novel inhibitor of the key DNA damage repair enzyme poly-ADP-ribose polymerase (PARP), which

also has an observed inhibitory action against Tankyrases, another important group of DNA damage repair enzymes.

Stenoparib was formerly

developed by Eisai, Inc.

(Eisai) through Phase 1 clinical trials, and we are currently advancing a Phase 2 clinical trial of this therapeutic

candidate for the treatment of ovarian cancer at trial sites in the U.S.

and Europe together with its stenoparib-specific DRP ®

companion diagnostic, for which the FDA has previously approved an Investigational Device Exemption (IDE) application.

In addition, subject

to funding, we anticipate commencing a stenoparib in combination with dovitinib Phase 1b/2 Clinical Trial for second-line or later treatment

of metastatic ovarian cancer and/or other solid tumors.

Our third priority therapeutic

candidate is IXEMPRA ® (ixabepilone), a selective microtubule inhibitor, which has been shown to interfere with cancer cell

division, leading to cell death.

IXEMPRA ® (ixabepilone) was formerly developed and brought to market by Bristol-Myers Squibb,

is currently marketed and sold in the U.S.

by R-PHARM US LLC, for the treatment of metastatic breast cancer treated with two or more prior

chemotherapies.

We are currently advancing IXEMPRA ® , together with its drug-specific DRP ® companion diagnostic,

in a Phase 2 European clinical trial for the same indication, with the goal of eventually submitting an application for Marketing Authorization

(MA) with the European Medicine Agency (EMA) to market IXEMPRA ® , together with its drug-specific DRP ® companion

diagnostic, in the European market.

We have in-licensed the intellectual

property rights to develop, use and market our two most advanced therapeutic candidates, dovitinib and stenoparib.

Consequently, we must

perform all of the obligations under these license agreements, including the payment of substantial development milestones payments and

royalty payments on future sales in the event we receive marketing approval for dovitinib or stenoparib in the future.

If we fail to perform

our obligations under our license agreements, we may lose the intellectual property rights to these therapeutic candidates which will

have a material adverse effect on our business.

Our focused approach to address

major unmet needs in oncology leverages our management’s expertise in discovery, medicinal chemistry, manufacturing, clinical development,

and commercialization.

As a result, we have created substantial intellectual property around the composition of matter for our new chemical

those patients who will and who will not respond to a cancer therapeutic, the DRP ® companion diagnostics platform has

the potential to transform cancer therapeutic development by isolating and enrolling only those patients most likely to receive benefit.

As a consequence, clinical trials can be smaller and more efficient and can provide profound clinical outcomes, enabling an enhanced

probability of clinical and regulatory success.

Stenoparib (formerly known as E7449 or 2X-121) is a novel dual inhibitor of poly-ADP-ribose

polymerase (PARP) as well as Tankyrases, enzymes critically important in the WNT pathway.

Stenoparib is currently being explored in a

phase 2 clinical study in patients with advanced, recurrent ovarian cancer who have been pre-selected for enrollment using the stenoparib

As per the press release from December 5, 2023, emerging clinical data from this trial in heavily pre-treated, advanced

ovarian cancer patients show promising clinical benefit across all evaluable patients and include a patient with complete response (i.e.

absence of active disease).

2023, Allarity seated two new independent directors to its board- Laura Benjamin, PhD and Joe Vazzano.

Along with the Chairman of the

board, Jerry McLaughlin, Dr.

Benjamin and Mr.

Vazzano took the decision to replace the CEO, Mr.

James Cullen, with Thomas Jensen.

Jensen serves as interim CEO and is a co-founder of Allarity.

He has extensive experience not only with the DRP ® platform

but also with capital fund raising.

Jensen is currently in the process of streamlining the organization and its finances to fuel

the focused development of stenoparib in ovarian cancer.

Corporate Approach to Developing Novel Cancer Therapeutics using the DRP ® Platform

focused approach to address major unmet needs in oncology leverages our management’s expertise in cancer drug discovery and development

and in deploying Allarity’s proprietary DRP ® platform to identify patients whose tumors have a particular gene expression

signature that reflects high likelihood of drug sensitivity.

As a result, we have created substantial intellectual property around the

composition of matter for our in-licensed clinical assets.

The foundations of our approach include:

The pursuit of

clinical-stage assets:

We strive to identify and pursue novel oncology therapeutic candidates that have advanced beyond

Phase 1 clinical trials and are preferably Phase 2 to Phase 3 clinical stage assets.

Accordingly, the assets we have acquired, and

intend to acquire, have undergone prior clinical trials by other pharmaceutical companies with clinical data that helps us evaluate

whether these candidates will be well tolerated in the tested patient population, and in some cases, have observed anti-cancer or

anti-tumor activity that would support additional clinical trials using our DRP® platform.

We often focus our acquisition

efforts on therapeutic candidates that have been the subject of clinical trials conducted by large pharmaceutical companies.

we intend to select therapeutic candidates for which we believe we can develop a drug-specific DRP ® to advance

together with the therapeutic candidate in further clinical trials as a companion diagnostic to select and treat the patients most

likely to respond to the therapeutic candidate.

We further consider whether the licensor or assignor can provide us substantial

clinical grade active pharmaceutical ingredients (API) for the therapeutic candidate, at low-to-no cost, for our use in future

clinical trials.

The availability of API at low-to-no cost reduces both our future clinical trial costs and the lead time it takes

us to start a new clinical trial for the therapeutic candidate.

As an example, our therapeutic candidate, dovitinib, was developed

by Novartis through Phase 2 clinical trials in numerous indications and in Phase 3 clinical trials for RCC before we acquired the

therapeutic candidate, and it came with a substantial API.

Our proprietary

DRP ® companion diagnostics:

We believe our proprietary and patented Drug Response Predictor

(DRP ® ) platform provides us with a substantial clinical and commercial competitive advantage for each of the

therapeutic candidates in our pipeline.

Our DRP ® companion diagnostic platform is a proprietary,

predictive biomarker technology that employs complex systems biology, bio-analytics with a proprietary clinical relevance filter to

bridge the gap between in vitro cancer cell responsiveness to a given therapeutic candidate and in vivo likelihood of actual patient

response to that therapeutic candidate.

The DRP ® companion diagnostic platform has been retrospectively validated by

us using retrospective observational studies in 35 clinical trials that were conducted or sponsored by other companies.

develop and validate a drug-specific DRP ® biomarker for each and every therapeutic candidate in our therapeutic

candidate pipeline to serve as a companion diagnostic to select and treat patients most likely to respond to that therapeutic

Although we are in the early stages of our companion diagnostic development and have not yet received a PMA from the FDA,

our DRP ® technology has been peer-reviewed by numerous publications and we have patented our DRP ®

platform for more than 70 anti-cancer drugs.

While retrospective studies guide our clinical development of our companion

diagnostics, prospective clinical trials may be required in order to receive a PMA from the FDA.

The pursuit of clinical-stage

We strive to identify and pursue novel oncology therapeutic candidates that have advanced beyond Phase 1 clinical

trials and are preferably Phase 2 to Phase 3 clinical stage assets.

Accordingly, the assets we have acquired, and intend to acquire,

have undergone prior clinical trials by other pharmaceutical companies.

The clinical data from these programs helps us evaluate whether

these candidates have shown anti-cancer activity that would support additional clinical trials in patients selected for clinical

study using our DRP ® platform.

We have largely focused our acquisition/ in-licensing efforts on therapeutic candidates

that have been the subject of prior clinical trials conducted by large pharmaceutical companies in unselected patient populations.

Further we intend to select therapeutic candidates for which development can be enhanced using our drug-specific DRP ®

technology to advance in parallel with the therapeutic candidate in further clinical trials as a companion diagnostic.

Our proprietary DRP ®

companion diagnostics:

We believe our proprietary and patented DRP ® platform provides us with a substantial

competitive advantage for clinical and regulatory success for each of the therapeutic candidates in our pipeline.

companion diagnostic platform is a proprietary, predictive biomarker technology that employs complex systems biology and bio-analytics

with a proprietary clinical relevance filter to bridge the gap between in vitro cancer cell responsiveness to a given therapeutic

candidate and in vivo likelihood of actual patient benefit from that therapeutic candidate.

The DRP ® companion

diagnostic platform has been validated using retrospective observational studies in 35 clinical trials that were conducted or sponsored

by other companies.

We intend to develop and validate a drug-specific DRP ® biomarker for each and every therapeutic

candidate in our portfolio that can be used as a companion diagnostic to select and treat patients most likely to respond to that

therapeutic candidate.

Although we are in the early stages of our companion diagnostic development and have not yet received a Pre-Marketing

Authorization (PMA) from the U.S.

Food and Drug Administration (FDA), our DRP ® technology has been peer-reviewed by

numerous publications and we have patented our DRP ® platform for more than 70 anti-cancer drugs.

While retrospective

analyses of prior clinical trials guide the clinical development of our companion diagnostics, prospective clinical trials are typically

required in order to receive a PMA from the FDA.

A precision oncology

Our focused strategy is to advance our pipeline of therapeutic candidates, together with DRP ®

companion diagnostics, to bring these therapeutic candidates, once approved, to market and to patients through a precision oncology

Our DRP ® companion diagnostic platform provides a gene expression fingerprint that we believe reveals

whether a specific tumor in a specific patient is likely to respond to one of our therapeutic candidates and therefore can be used

to identify those patients who are most likely to respond to a particular therapeutic treatment in order to guide therapy decisions

and lead to better treatment outcomes.

We believe our DRP ® companion diagnostic platform may be used both to identify

a susceptible patient population for inclusion in clinical trials during the drug development process (and to exclude the

non-susceptible patient population), and further to select the optimal anti-cancer drug for individual patients in the treatment

approach driven by our DRP ® platform :

Our focused strategy is to advance our pipeline of therapeutic

candidates, in parallel with DRP ® companion diagnostics, to bring these therapeutic candidates, once approved, to

market and to patients.

Our DRP ® companion diagnostic platform provides a gene expression signature that we believe

reveals whether a specific tumor in a specific patient is likely to respond to one of our therapeutic candidates and therefore can

be used to identify those patients who are most likely to respond to a particular therapeutic treatment in order to guide therapy

decisions and lead to better treatment outcomes.

We believe our DRP ® companion diagnostic platform may be used both

to identify a susceptible patient population for inclusion in clinical trials during the drug development process (and to exclude

the non-susceptible patient population), and further to select the optimal anti-cancer drug for individual patients in the treatment

setting once an anti-cancer drug is approved and marketed.

By including only patients that have tumors that we believe may respond

to our therapeutic candidate in our clinical trials, we believe our proprietary DRP ® companion diagnostics platform

has the potential to improve the overall treatment response in our clinical trials and thereby improving our chances for regulatory

approval to market our therapeutic candidate, while potentially reducing the time, cost, and risk of clinical

The following chart summarizes

our therapeutic candidate pipeline:

Implications of Being an Emerging Growth Company

and a Smaller Reporting Company

We are an “emerging

growth company,” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and we intend to take advantage

of certain exemptions from various reporting requirements that are applicable to other public companies that are not “emerging growth

companies” including not being required to comply with the auditor attestation requirements of Section 404(b) of the Sarbanes-Oxley

Act, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements, and exemptions from

the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any golden parachute payments

not previously approved.

In addition, Section 107 of the JOBS Act also provides that an “emerging growth company” can take

advantage of the extended transition period provided in Section 7(a)(2)(B) of the Securities Act, for complying with new or revised accounting

Additionally, we are a “smaller

reporting company” as defined in Item 10(f)(1) of Regulation S-K.

Even after we no longer qualify as an emerging growth company,

we may still qualify as a “smaller reporting company,” which would allow us to continue to take advantage of many of the same

exemptions from disclosure requirements, including presenting only the two most recent fiscal years of audited financial statements and

reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements.

We may continue to be a

smaller reporting company if either (i) the market value of our stock held by non-affiliates is less than $250 million or (ii) our annual

revenue was less than $100 million during the most recently completed fiscal year and the market value of our stock held by non-affiliates

is less than $700 million.

To the extent we take advantage of such reduced disclosure obligations, it may also make comparison of our

financial statements with other public companies difficult or impossible.

Corporate Information

Our former parent, Allarity

Therapeutics A/S, was founded in Denmark in 2004 by our chief scientific officer, Steen Knudsen, Ph.D., and our Director and Senior Vice

President of Investor Relations, Thomas Jensen, both of whom were formerly academic researchers at the Technical University of Denmark

working to advance novel bioinformatic and diagnostic approaches to improving cancer patient response to therapeutics.

On May 20, 2021,

we entered a Plan of Reorganization and Asset Purchase Agreement (the “Recapitalization Share Exchange”), between us, Allarity

Acquisition Subsidiary, our wholly owned Delaware subsidiary (“Acquisition Sub”), and Allarity Therapeutics A/S, an Aktieselskab

organized under the laws of Denmark.

Pursuant to the terms of the Recapitalization Share Exchange, our Acquisition Sub acquired substantially

all of the assets and liabilities of Allarity Therapeutics A/S in exchange for shares of our common stock on December 20, 2021, and our

common stock began trading on the Nasdaq Global Market on that same day.

See section titled “ BUSINESS — Recapitalization

Share Exchange, Asset Acquisition and Financing.

Our principal executive offices

are located at 24 School Street, 2nd Floor, Boston, MA 02108 and our telephone number is (401) 426-4664.

Our corporate website

address is www.allarity.com .

Information contained on or accessible through our website is not a part of this report, and the inclusion

of our website address in this report is an inactive textual reference only.

Allarity and its subsidiaries

own or have rights to trademarks, trade names and service marks that they use in connection with the operation of their business.

their names, logos and website names and addresses are their trademarks or service marks.

Other trademarks, trade names and service marks

appearing in this report are the property of their respective owners.

Solely for convenience, in some cases, the trademarks, trade names

and service marks referred to in this report are listed without the applicable ® , ™ and SM symbols,

but they will assert, to the fullest extent under applicable law, their rights to these trademarks, trade names and service marks.

This Annual Report contains

estimates, projections and other information concerning our industry, our business and the markets for our therapeutic candidates, including

data regarding the estimated size of such markets and the incidence of certain medical conditions.

We obtained the industry, market and

similar data set forth in this Annual Report from our internal estimates and research and from academic and industry research, publications,

surveys and studies conducted by third parties, including governmental agencies.

In some cases, we do not expressly refer to the sources

from which this data is derived.

Information that is based on estimates, forecasts, projections, market research or similar methodologies

is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances that are

assumed in this information.

While we believe our internal research is reliable, such research has not been verified by any third party.

We are a clinical stage pharmaceutical

company targeting some of the greatest unmet needs in oncology by developing differentiated and novel therapeutic candidates together

with our proprietary DRP ® companion diagnostics in a precision medicine approach.

Our business strategy includes a focus

on leveraging our proprietary DRP ® companion diagnostics platform to streamline the drug development process and to identify

patients that will benefit from therapeutic candidates that other biotechnology or pharmaceutical companies have abandoned or shelved

after initiating clinical trials under an IND application filed with the FDA, including candidates that have failed to achieve statistical

significance on the original endpoints established in their clinical trials.

We use our proprietary DRP ® companion diagnostics

platform to advance therapeutic candidates by targeting and evaluating patient sub-populations having gene signatures, determined by our

DRP ® companion diagnostics platform, that will potentially correlate with drug efficacy and patient response to treatment.

While we have not yet successfully received regulatory or marketing approval for any of our therapeutic candidates or companion diagnostics,

to our therapeutic candidate, we believe our proprietary DRP ® companion diagnostics platform has the potential to

improve the overall clinical benefit in our clinical trials and thereby improving our chances for regulatory approval to market our

therapeutic candidate, while potentially reducing the time, cost, and risk of clinical development.

we have not yet successfully received regulatory or marketing approval for any of our therapeutic candidates or companion diagnostics,

and while we believe that our approach has the potential to reduce the cost and time of drug development through the identification and

selection of patient populations more likely to respond to therapy, our strategy involves risks and uncertainties that differ from other

biotechnology companies that focus solely on new therapeutic candidates that do not have a history of failed clinical development.

utilizing our DRP ® platform to generate a drug-specific companion diagnostic for each of our therapeutic candidates, if

approved by the FDA, we believe our therapeutic candidates have the potential to advance the goal of personalized medicine by selecting

the patients most likely to benefit from each of our therapeutic candidates and avoid the treatment of non-responder patients.

our therapeutic candidates are clinical stage assets and the FDA has not yet approved any of our therapeutic candidates or any of our

DRP ® companion diagnostics.

As used in this report, statements regarding the use of our proprietary DRP ®

companion diagnostics or our proprietary DRP ® platform or our observations that a therapeutic candidate may have anti-cancer

or anti-tumor activity or is observed to be well tolerated in a patient population should not be construed to mean that we have resolved

all issues of safety and/or efficacy for any of our therapeutic candidates or DRP ® companion diagnostic.

Issues of safety

and efficacy for any therapeutic candidate or companion diagnostic may only be determined by the U.S.

FDA or other applicable regulatory

authorities in jurisdictions outside the United States.

Our Corporate History

We were founded in Denmark

in 2004 by our chief scientific officer, Steen Knudsen, Ph.D., and our Director and Senior Vice President of Investor Relations, Thomas

Jensen, both of whom were formerly academic researchers at the Technical University of Denmark working to advance novel bioinformatic

and diagnostic approaches to improving cancer patient response to therapeutics.

On May 20, 2021, we entered a Plan of Reorganization and

Asset Purchase Agreement (the “Recapitalization Share Exchange”), between us, Allarity Acquisition Subsidiary, our wholly

owned Delaware subsidiary (“Acquisition Sub”), and Allarity Therapeutics A/S, an Aktieselskab organized under the laws of

Pursuant to the terms of the Recapitalization Share Exchange, our Acquisition Sub acquired substantially all of the assets and

liabilities of Allarity Therapeutics A/S in exchange for shares of our common stock on December 20, 2021, and our common stock began trading

on Nasdaq on that same day.

See “ BUSINESS - Recapitalization Share Exchange, Asset Acquisition and Financing .” Concurrently,

on December 21, 2021, we completed a private placement of our Series A Preferred Stock and a warrant to purchase additional shares of

our common stock for an aggregate purchase price of $20.0 million.

Our DRP ® companion

diagnostic platform has been retrospectively validated by us using retrospective observational studies in 35 clinical trials that

were conducted or sponsored by other companies.

The FDA considers a retrospective observational study to be one in which the study identifies

the population and determines the exposure/treatment from historical data (i.e.

data generated prior to the initiation of the study) with

the variables and outcomes of interest determined at the time the study is designed.

See, Framework for FDA’s Real-World Evidence

Program, page 6 (December 2018), https://www.fda.gov/media/120060/download .

The FDA has accepted our retrospective validation

in support of two Investigational Device Exemption (“IDE”) applications to conduct clinical trials, one with respect to LiPlaCis ®

and one with respect to stenoparib.

However, while retrospective studies guide our clinical development of our companion diagnostics,

prospective clinical trials may be required in order to receive a PMA from the FDA.

We submitted a New Drug Application

(NDA) to the U.S.

Food and Drug Administration (FDA) for our therapeutic candidate, dovitinib, a second-generation “pan”-tyrosine

biotechnology companies that focus solely on new therapeutic candidates that do not have a history of clinical development.

our DRP ® platform to generate a drug-specific companion diagnostic for each of our therapeutic candidates, we believe

our therapeutic candidates have the potential to advance the goal of personalized medicine by selecting only the patients most likely

to benefit from each of our therapeutic candidates.

Moreover, this pre-selection excludes patients who are unlikely to get benefit from

a specific therapy, allowing those patients to find more effective therapeutic options.

As used in this report, statements regarding

the use of our proprietary DRP ® companion diagnostics or our proprietary DRP ® platform or our observations

that a therapeutic candidate may have anti-cancer or anti-tumor activity or is observed to be well tolerated in a patient population

should not be construed to mean that we have resolved all issues of safety and/or efficacy for any of our therapeutic candidates or DRP ®

companion diagnostic.

Issues of safety and efficacy for any therapeutic candidate or companion diagnostic may only be determined

by the FDA or other applicable regulatory authorities in jurisdictions outside the United States.

Lead Clinical Asset, Stenoparib

is a novel inhibitor of the key DNA damage repair enzyme PARP.

Distinct from other PARP inhibitors, stenoparib also inhibits Tankyrases,

enzymes critically important in the WNT pathway- a pathway commonly activated in many different cancers that drives cancer cell survival

and proliferation as well as invasion and metastasis.

Stenoparib was formerly developed by Eisai, Inc.

(Eisai) through Phase 1 clinical

We have in-licensed the intellectual property rights to develop, use and market stenoparib.

Consequently, we must perform all

of the obligations under these license agreements, including the payment to Esai pharmaceuticals of substantial development milestones

and royalties on future sales in the event we receive marketing approval for stenoparib.

If we fail to perform our obligations under

our license agreement, we may lose the intellectual property rights to this therapeutic candidate, which would have a material adverse

effect on our business.

We are currently advancing a Phase 2 clinical trial of this therapeutic candidate for the treatment of ovarian

cancer at trial sites in the U.S.

and Europe together using the stenoparib-specific DRP ® companion diagnostic for which

the FDA has previously approved an Investigational Device Exemption (IDE) application to prospectively enroll patients onto clinical

of Being an Emerging Growth Company and a Smaller Reporting Company

are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and we

intend to take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that

are not “emerging growth companies” including not being required to comply with the auditor attestation requirements of Section

404(b) of the Sarbanes-Oxley Act, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements,

and exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any

golden parachute payments not previously approved.

In addition, Section 107 of the JOBS Act also provides that an “emerging growth

company” can take advantage of the extended transition period provided in Section 7(a)(2)(B) of the Securities Act, for complying

with new or revised accounting standards.

Additionally,

we are a “smaller reporting company” as defined in Item 10(f)(1) of Regulation S-K.

Even after we no longer qualify as an

emerging growth company, we may still qualify as a “smaller reporting company,” which would allow us to continue to take

advantage of many of the same exemptions from disclosure requirements, including presenting only the two most recent fiscal years of

audited financial statements and reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements.

We may continue to be a smaller reporting company if either (i) the market value of our stock held by non-affiliates is less than $250

million or (ii) our annual revenue was less than $100 million during the most recently completed fiscal year and the market value of

our stock held by non-affiliates is less than $700 million.

To the extent we take advantage of such reduced disclosure obligations, it

may also make comparison of our financial statements with other public companies difficult or impossible.

former parent, Allarity Therapeutics A/S, was founded in Denmark in 2004 by our chief scientific officer, Steen Knudsen, Ph.D., and our

Interim Chief Executive Officer, Director and Senior Vice President of Investor Relations, Thomas Jensen, both of whom were formerly

academic researchers at the Technical University of Denmark working to advance novel bioinformatic and diagnostic approaches to improving

cancer patient response to therapeutics.

On May 20, 2021, we entered a Plan of Reorganization and Asset Purchase Agreement (the “Recapitalization

Share Exchange”), between us, Allarity Acquisition Subsidiary, our wholly owned Delaware subsidiary (“Acquisition Sub”),

and Allarity Therapeutics A/S, an Aktieselskab organized under the laws of Denmark.

Pursuant to the terms of the Recapitalization Share

Exchange, our Acquisition Sub acquired substantially all of the assets and liabilities of Allarity Therapeutics A/S in exchange for shares

of our common stock on December 20, 2021, and our common stock began trading on the Nasdaq Global Market on that same day.

titled “ BUSINESS — Recapitalization Share Exchange, Asset Acquisition and Financing.

principal executive offices are located at 24 School Street, 2nd Floor, Boston, MA 02108 and our telephone number is (401) 426-4664.

corporate website address is www.allarity.com .

Information contained on or accessible through our website is not a part of this

report, and the inclusion of our website address in this report is an inactive textual reference only.

and its subsidiaries own or have rights to trademarks, trade names and service marks that they use in connection with the operation of

their business.

In addition, their names, logos and website names and addresses are their trademarks or service marks.

Other trademarks,

trade names and service marks appearing in this report are the property of their respective owners.

Solely for convenience, in some cases,

the trademarks, trade names and service marks referred to in this report are listed without the applicable ® , ™ and

SM symbols, but they will assert, to the fullest extent under applicable law, their rights to these trademarks, trade names and service

Annual Report contains estimates, projections and other information concerning our industry, our business and the markets for our therapeutic

candidates, including data regarding the estimated size of such markets and the incidence of certain medical conditions.

the industry, market and similar data set forth in this Annual Report from our internal estimates and research and from academic and

industry research, publications, surveys and studies conducted by third parties, including governmental agencies.

In some cases, we do

not expressly refer to the sources from which this data is derived.

Information that is based on estimates, forecasts, projections, market

research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from

events and circumstances that are assumed in this information.

While we believe our internal research is reliable, such research has

not been verified by any third party.

Corporate History

were founded in Denmark in 2004 by our chief scientific officer, Steen Knudsen, Ph.D., and our Interim Chief Executive Officer, Director,

and Senior Vice President of Investor Relations, Thomas Jensen, both of whom were formerly academic researchers at the Technical University

of Denmark working to advance novel bioinformatic and diagnostic approaches to improving cancer patient response to therapeutics.

May 20, 2021, we entered a Plan of Reorganization and Asset Purchase Agreement (the “Recapitalization Share Exchange”), between

us, Allarity Acquisition Subsidiary, our wholly owned Delaware subsidiary (“Acquisition Sub”), and Allarity Therapeutics

A/S, an Aktieselskab organized under the laws of Denmark.

Pursuant to the terms of the Recapitalization Share Exchange, our Acquisition

Sub acquired substantially all of the assets and liabilities of Allarity Therapeutics A/S in exchange for shares of our common stock

on December 20, 2021, and our common stock began trading on Nasdaq on that same day.

DRP ® companion diagnostic platform has been retrospectively validated by us using retrospective observational studies

in 35 clinical trials that were conducted or sponsored by other companies.

The FDA considers a retrospective observational study

to be one in which the study identifies the population and determines the exposure/treatment from historical data (i.e.

data generated

prior to the initiation of the study) with the variables and outcomes of interest determined at the time the study is designed.

Framework for FDA’s Real-World Evidence Program, page 6 (December 2018), https://www.fda.gov/media/120060/download .

The FDA has accepted our retrospective validation in support of two IDE applications to conduct clinical trials, one with respect to

LiPlaCis ® and one with respect to stenoparib.

However, while retrospective studies guide our clinical development of our

companion diagnostics, prospective clinical trials are typically required in order to receive a PMA from the FDA.

submitted a New Drug Application (NDA) to the FDA for our now de-prioritized therapeutic candidate, dovitinib, a second-generation “pan”-tyrosine

kinase inhibitor (TKI), on December 21, 2021, for the third line treatment of mRCC in patients selected by our Dovitinib-DRP ®

companion diagnostic.

Subsequently the FDA determined that our NDA was not sufficiently complete to permit a substantive review and therefore

or NDA was not accepted for filing.

The primary grounds of rejection asserted by the FDA relates to our use of prior Phase 3 clinical

trial data, generated by Novartis in a “superiority” endpoint study against sorafenib (Bayer), to support a “non-inferiority”

Subsequently the FDA determined that our NDA was not sufficiently complete to permit a substantive review

and therefore or NDA was not accepted for filing.

The primary grounds of rejection asserted by the FDA relates to our use of prior Phase

3 clinical trial data, generated by Novartis in a “superiority” endpoint study against sorafenib (Bayer), to support a “non-inferiority”

endpoint in connection with the DRP ® Dovitinib companion diagnostic.

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diagnostic Dovitinib-DRP can be obtained.

While we have decided that the costs, risks and potential benefits of conducting these studies

for dovitinib as a monotherapy for mRCC are no longer the best path toward commercial success, we continue to evaluate other potential

Phase 1b/2 clinical trials for dovitinib combined with other approved drugs in the mRCC space and in other indications.

For example, subject

to funding we anticipate commencing a stenoparib in combination with dovitinib Phase 1b/2 clinical trial for second-line or later treatment

of metastatic ovarian cancer and/or other solid tumors.

Our decision to advance dovitinib as a combination therapy and not as a monotherapy

is based on our belief that both the science and the market for oncology therapies has shifted towards combination therapies and away

from monotherapies for multiple indications of cancer.

We further believe that our DRP ® -Dovitinib companion diagnostic

is tumor agnostic and our retrospective analysis of the clinical data generated in the Novartis clinical studies for mRCC will also support

a companion diagnostic for dovitinib in second-line or later treatment of metastatic ovarian cancer, as well as other indications.

While we have suffered delays

due to the COVID-19 pandemic, we continue to expand patient enrollment in our ongoing Phase 2 clinical trials for our two other priority

programs, stenoparib, a novel inhibitor of the key DNA damage repair enzyme poly-ADP-ribose polymerase (PARP), and IXEMPRA ®

(ixabepilone), a selective microtubule inhibitor.

We also intend to opportunistically acquire other promising oncology assets, which have

undergone prior clinical trials by other pharmaceutical companies with clinical data that helps us evaluate whether these candidates will

be well tolerated in the tested patient population, and in some cases, have observed anti-cancer or anti-tumor activity that would support

additional clinical trials using our DRP ® platform.

Our clinical and commercial

development team is advancing our pipeline of targeted oncology therapeutic candidates, all of which have previously succeeded at least

through Phase 1 clinical demonstrating that the therapeutic candidate is well tolerated.

Our three priority assets, dovitinib, stenoparib,

and IXEMPRA ® (ixabepilone) are all former drug candidates of large pharmaceutical companies.

Our most advanced therapeutic

candidate, dovitinib, is a selective inhibitor of several classes of tyrosine kinases, including FGFR and VEGFR, and was formerly developed

by Novartis Pharmaceuticals through Phase 3 clinical trials in numerous indications.

As mentioned above, we submitted an NDA with the

FDA on December 21, 2021, for the third line treatment of mRCC in patients selected by our Dovitinib-DRP ® companion diagnostic.

Prior to submission of the NDA, we submitted a Pre-Market Approval (PMA) application to the FDA for approval of our dovitinib-specific

DRP ® companion diagnostic for use to select and treat patients likely to respond to dovitinib.

On February 15, 2022, we

received RTF letters for both our dovitinib NDA and our DRP ® -Dovitinib companion diagnostic PMA.

The FDA has asserted that

neither our NDA or PMA meets the regulatory requirements to warrant a complete agency review.

The primary grounds of rejection asserted

by the FDA relates to our use of prior Phase 3 clinical trial data, generated by Novartis in a “superiority” endpoint study

against sorafenib (Bayer), to support a “non-inferiority” endpoint and superiority in connection with the DRP ® -Dovitinib

companion diagnostic.

We anticipate that it will be necessary to conduct a new prospective Phase 3 clinical trial, as well as additional

dosing studies, to gain approval of dovitinib in the U.S.

as a monotherapy for mRCC.

While we have decided that the costs, risks and potential

benefits of conducting these studies for dovitinib as a monotherapy for mRCC are no longer the best path toward commercial success, we

continue to evaluate other potential Phase 1b/2 clinical trials for dovitinib combined with other approved drugs in the mRCC space and

in other indications.

For example, subject to funding we anticipate commencing a stenoparib in combination with dovitinib Phase 1b/2 clinical

trial for second-line or later treatment of metastatic ovarian cancer and/or other solid tumors.

Our decision to advance dovitinib as

a combination therapy and not as a monotherapy is based on our belief that both the science and the market for oncology therapies has

shifted towards combination therapies and away from monotherapies for multiple indications of cancer.

We further believe that our DRP ® -Dovitinib

companion diagnostic is tumor agnostic and our retrospective analysis of the clinical data generated in the Novartis clinical studies

for mRCC will also support a companion diagnostic for dovitinib in second-line or later treatment of metastatic ovarian cancer, as well

as other indications.

Our second priority therapeutic

candidate is stenoparib (formerly E7449), a novel inhibitor of the key DNA damage repair enzyme poly-ADP-ribose polymerase (PARP), which

also has an observed inhibitory action against Tankyrases, another important group of DNA damage repair enzymes.

Stenoparib was formerly

developed by Eisai, Inc.

(Eisai) through Phase 1 clinical trials, and we are currently advancing a Phase 2 clinical trial of this therapeutic

candidate for the treatment of ovarian cancer at trial sites in the U.S.

and Europe) together with its stenoparib-specific DRP ®

companion diagnostic, for which the FDA has previously approved an Investigational Device Exemption (IDE) application.

As mentioned above,

subject to funding we anticipate commencing a stenoparib in combination with dovitinib Phase 1b/2 clinical trial for second-line or later

treatment of metastatic ovarian cancer and/or other solid tumors.

Our third priority therapeutic

candidate is IXEMPRA ® (ixabepilone), a selective microtubule inhibitor, which has been shown to interfere with cancer cell

division, leading to cell death.

IXEMPRA ® (ixabepilone) was formerly developed and brought to market by Bristol-Myers Squibb,

is currently marketed and sold in the U.S.

by R-PHARM US LLC, for the treatment of metastatic breast cancer treated with two or more prior

chemotherapies.

We are currently advancing IXEMPRA ® , together with its drug-specific DRP ® companion diagnostic,

in a Phase 2 European clinical trial for the same indication, with the goal of eventually submitting an application for Marketing Authorization

(MA) with the European Medicine Agency (EMA) to market IXEMPRA ® , together with its drug-specific DRP ® companion

diagnostic, in the European market.

We have in-licensed the intellectual

property rights to develop, use and market our two lead therapeutic candidates, dovitinib and stenoparib.

Consequently, we must perform

all of the obligations under these license agreements, including the payment of substantial development milestones payments and royalty

payments on future sales in the event we receive marketing approval for dovitinib or stenoparib in the future.

If we fail to perform our

obligations under our license agreements, we may lose the intellectual property rights to these therapeutic candidates which will have

a material adverse effect on our business.

Our focused approach to address

major unmet needs in oncology leverages our management’s expertise in discovery, medicinal chemistry, manufacturing, clinical development,

and commercialization.

As a result, we have created substantial intellectual property around the composition of matter for our new chemical

The foundations of our approach include:

The pursuit of

clinical-stage assets:

We strive to identify and pursue novel oncology therapeutic candidates that have advanced beyond

Phase 1 clinical trials and are preferably Phase 2 to Phase 3 clinical stage assets.

Accordingly, the assets we have acquired, and

intend to acquire, have undergone prior clinical trials by other pharmaceutical companies with clinical data that helps us evaluate

whether these candidates will be well tolerated in the tested patient population, and in some cases, have observed anti-cancer or

anti-tumor activity that would support additional clinical trials using our DRP® platform.

We often focus our acquisition

efforts on therapeutic candidates that have been the subject of clinical trials conducted by large pharmaceutical companies.

we intend to select therapeutic candidates for which we believe we can develop a drug-specific DRP ® to advance

together with the therapeutic candidate in further clinical trials as a companion diagnostic to select and treat the patients most

likely to respond to the therapeutic candidate.

We further consider whether the licensor or assignor can provide us substantial

clinical grade active pharmaceutical ingredients (API) for the therapeutic candidate, at low-to-no cost, for our use in future

clinical trials.

The availability of API at low-to-no cost reduces both our future clinical trial costs and the lead time it takes

us to start a new clinical trial for the therapeutic candidate.

As an example, our therapeutic candidate, dovitinib, was developed

by Novartis through Phase 2 clinical trials in numerous indications and in Phase 3 clinical trials for RCC before we acquired the

therapeutic candidate, and it came with a substantial API.

Our proprietary

DRP ® companion diagnostics:

We believe our proprietary and patented Drug Response Predictor

(DRP ® ) platform provides us with a substantial clinical and commercial competitive advantage for each of therapeutic

candidates in our pipeline.

Our DRP ® companion diagnostic platform is a proprietary, predictive biomarker

technology that employs complex systems biology, bio-analytics with a proprietary clinical relevance filter to bridge the gap

between in vitro cancer cell responsiveness to a given therapeutic candidate and in vivo likelihood of actual patient response to

that therapeutic candidate.

The DRP ® companion diagnostic platform has been retrospectively validated by us using

retrospective observational studies in 35 clinical trials that were conducted or sponsored by other companies.

We intend to develop

and validate a drug-specific DRP ® biomarker for each and every therapeutic candidate in our therapeutic candidate

pipeline to serve as a companion diagnostic to select and treat patients most likely to respond to that therapeutic candidate.

Although we are in the early stages of our companion diagnostic development and have not yet received a PMA from the FDA, our

DRP ® technology has been peer-reviewed by numerous publications and we have patented our DRP ® platform

for more than 70 anti-cancer drugs.

While retrospective studies guide our clinical development of our companion

diagnostics, prospective clinical trials may be required in order to receive a PMA from the FDA.

A precision oncology

Our focused strategy is to advance our pipeline of therapeutic candidates, together with DRP ®

companion diagnostics, to bring these therapeutic candidates, once approved, to market and to patients through a precision oncology

Our DRP ® companion diagnostic platform provides a gene expression fingerprint that we believe reveals

whether a specific tumor in a specific patient is likely to respond to one of our therapeutic candidates and therefore can be used

to identify those patients who are most likely to respond to a particular therapeutic treatment in order to guide therapy decisions

and lead to better treatment outcomes.

We believe our DRP ® companion diagnostic platform may be used both to identify

a susceptible patient population for inclusion in clinical trials during the drug development process (and to exclude the

non-susceptible patient population), and further to select the optimal anti-cancer drug for individual patients in the treatment

setting once an anti-cancer drug is approved and marketed.

By including only patients that have tumors that we believe may respond

to our therapeutic candidate in our clinical trials, we believe our proprietary DRP ® companion diagnostics platform

has the potential to improve the overall treatment response in our clinical trials and thereby improving our chances for regulatory

approval to market our therapeutic candidate, while potentially reducing the time, cost, and risk of clinical

The following chart summarizes

our therapeutic candidate pipeline:

Recapitalization Share Exchange, Asset Acquisition and Financing

We were previously known as

Oncology Venture A/S and changed our name to Allarity Therapeutics A/S on October 7, 2020.

On April 6, 2021, we incorporated Allarity

Therapeutics, Inc., a Delaware corporation, for the purposes of undertaking a recapitalization share exchange, a private placement of

our preferred stock with an institutional investor (the “PIPE Financing”), and migrating the trading in our shares from the

Nasdaq First North Growth Market:

Stockholm to Nasdaq in the U.S.

On May 20, 2021, we entered into a Plan of Reorganization and Asset

Purchase Agreement (the “Recapitalization Share Exchange”), which was amended and restated on September 23, 2021, between

us, Allarity Acquisition Subsidiary, our wholly owned Delaware subsidiary (“Acquisition Sub”), and Allarity Therapeutics A/S,

an Aktieselskab organized under the laws of Denmark (“Allarity Therapeutics A/S, or Allarity A/S”), subject to the

approval of the Recapitalization Share Exchange at an Extraordinary General Meeting (the “EGM”) of the shareholders of Allarity

The shareholders of Allarity A/S approved the Recapitalization Share Exchange at the EGM on November 22, 2021.

On December 17, 2021

and in connection with the Recapitalization Share Exchange, we entered into the Asset Purchase Agreement with our Acquisition Sub and

Allarity A/S, pursuant to which Allarity A/S agreed to sell, and our Acquisition Sub agreed to purchase, all of Allarity A/S’ assets

and certain specified liabilities in connection with Allarity A/S’ Business (as defined in the Asset Purchase Agreement), for an

aggregate purchase price of 8,075,824 shares of our common stock, plus the assumption of the specified liabilities.

On December 20, 2021, we consummated

the transactions contemplated in the Asset Purchase Agreement, pursuant to which our Acquisition Sub acquired substantially all of the

assets and assumed substantially all of the liabilities of Allarity A/S.

In connection with the closing, our Acquisition Sub acquired

substantially all of the assets and liabilities of Allarity A/S in exchange for shares of our common stock issued pursuant to a Registration

Statement on Form S-4 (SEC File No.

333-258968), which was declared effective on November 5, 2021.

Upon the closing of the Recapitalization

Share Exchange, all of the shareholders of Allarity A/S became our shareholders, owning substantially the same percentage ownership in

us as they owned in Allarity A/S.

All of the business previously owned by Allarity A/S is owned and conducted by us through our Acquisition

Because we were formed as

a “business combination related shell company” as defined in SEC Rule 405 for the purposes of undertaking our Recapitalization

Share Exchange, Allarity Therapeutics A/S, our former parent who became our predecessor upon consummation of the Recapitalization Share

Exchange, was deemed to be the accounting acquirer in the Recapitalization Share Exchange.

While we are the legal acquirer of Allarity

Therapeutics A/S in the Recapitalization Share Exchange, because Allarity Therapeutics A/S is deemed to be the accounting acquirer, the

historical consolidated financial statements of Allarity Therapeutics A/S became our historical consolidated financial statements upon

the consummation of the Recapitalization Share Exchange.

The Private Placement (PIPE Financing)

Concurrently with the execution

of the Recapitalization Share Exchange on May 20, 2021, we entered into a Securities Purchase Agreement (“SPA”) and related

agreements with an institutional investor (the “Investor”) wherein we agreed to sell, and the Investor agreed to purchase,

20,000 shares of our Series A Preferred Stock and a warrant to purchase additional shares of our common stock (the “PIPE Warrant”)

for an aggregate purchase price of $20 million with a closing conditioned upon the consummation of our Recapitalization Share Exchange

and a listing of our common stock on Nasdaq.

Simultaneously with the execution of the SPA, we also entered into a Registration Rights

Agreement (“RRA”) with the Investor wherein we agreed to register a number of shares of our common stock equal to the maximum

number of shares of our common stock that could be issued upon conversion of the Series A Preferred Stock using a conversion price equal

to 20% of $80,000,000 divided by the number of shares of common stock then outstanding (the “Floor Price”) price plus 125%

of the shares of common stock issuable upon exercise of the PIPE Warrant, or a maximum of 12,618,590 shares of our common stock.

shares were registered for resale on a Registration Statement on Form S-1 originally filed with the SEC on September 13, 2021 (SEC File

We have decided that the costs, risks and potential benefits of conducting these studies for

dovitinib as a monotherapy for mRCC are no longer the best path toward regulatory or commercial success.

we have suffered delays due to the COVID-19 pandemic, we continue to expand patient enrollment in our ongoing Phase 2 clinical trial

for our priority program, stenoparib, a novel dual inhibitor of the key DNA damage repair enzyme PARP, as well as tankyrases, key enzymes

in the WNT pathway implicated in many cancer types.

We also intend to opportunistically acquire other promising oncology assets that

can benefit from DRP ® platform based patient identification.

Our programs for dovitinib and Ixempra have been de-prioritized.

Novartis has terminated the license agreement for dovitinib.

These pro-active decisions to trim the pipeline allow us to funnel all resources

into the development of stenoparib.

Private Placement (PIPE Financing)

with the execution of the Recapitalization Share Exchange on May 20, 2021, we entered into a Securities Purchase Agreement (“SPA”)

and related agreements with an institutional investor (the “Investor”) wherein we agreed to sell, and the Investor agreed

to purchase, 20,000 shares of our Series A Preferred Stock and a warrant to purchase additional shares of our common stock (the “PIPE

Warrant”) for an aggregate purchase price of $20 million with a closing conditioned upon the consummation of our Recapitalization

Share Exchange and a listing of our common stock on Nasdaq.

Simultaneously with the execution of the SPA, we also entered into a Registration

Rights Agreement (“RRA”) with the Investor wherein we agreed to register a number of shares of our common stock equal to

the maximum number of shares of our common stock that could be issued upon conversion of the Series A Preferred Stock using a conversion

price equal to 20% of $80,000,000 divided by the number of shares of common stock then outstanding (the “Floor Price”) price

plus 125% of the shares of common stock issuable upon exercise of the PIPE Warrant, or a maximum of 12,618,590 shares of our common stock.

Such shares were registered for resale on a Registration Statement on Form S-1 originally filed with the SEC on September 13, 2021 (SEC

333-259484), which was declared effective on December 20, 2021.

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Amount of the Series A Preferred Stock, as more specifically described below.

Simultaneously with the closing

of its Recapitalization Share Exchange, we closed on the PIPE Investment pursuant to the SPA.

On December 20, 2021, we issued 20,000 shares

of Series A Preferred Stock at $1,000 per share and a common stock purchase warrant to purchase 2,018,958 shares of common stock at an

initial exercise price of $9.9061 to the Investor for an aggregate purchase price of $20 million.

Each share of Series A Preferred Stock

has a right to convert into shares of our common stock at an initial fixed conversion price of $9.9061.

However, if (i) the price of our

shares of common stock trade below $9.9061 (a “Price Failure”) for a specified period of time;

or (ii) in the event that the

sum of (x) the aggregate daily dollar trading volume (as reported on Bloomberg) of our common stock on Nasdaq during the 10 trading day

period ending on the trading day immediately preceding such date of determination, divided by (y) 10, is less than $1,500,000 (a “Volume

Maximum Failure”), each share of Series A Preferred Stock is entitled to convert at a price equal to 90% of the sum of the two lowest

VWAPs during the ten (10) trading day period immediately preceding delivery divided by two (the “90% Conversion Price”), but

not less than the Floor Price, or, at the time of such Price Failure or Volume Maximum Failure, the sum of the average daily U.S.

volume for our common stock during the 10 days previous to conversion divided by 10 is less than $2,000,000 (a “Volume Alternate

Failure”), then each share of Series A Preferred Stock is entitled to convert at the lower of the fixed conversion price or a price

equal to 80% of the sum of the two lowest VWAPs during the 10 trading day period immediately preceding delivery divided by two (the “80%

Conversion Price”), but not less than the Floor Price (such 90% Conversion Price or 80% Conversion Price, as the case may be, the

“Alternate Conversion Price”).

If certain defined “Triggering Events” defined in the Certificate of Designations

occur, such as a breach of the Registration Rights Agreement, suspension of trading, or our failure to convert the Series A Preferred

Stock into common stock when a conversion right is exercised, failure to issue our common stock when the PIPE Warrant is exercised, failure

to declare and pay to any holder any dividend on any dividend date, certain defaults on our debts or contractual obligations, or upon

a “bankruptcy triggering event” (as defined in the Certificate of Designations), then we may be required to pay a dividend

that is added to the stated value on the Series A Preferred Stock in the amount of 18% per annum, but paid quarterly in cash, so long

as the triggering event is continuing, or to redeem the Series A Preferred Stock for cash in an amount of a minimum of 125% of the Conversion

Amount (as defined in the Certificate of Designations) of the Series A Preferred Stock or 125% of the Conversion Amount of the Series

A Preferred Stock would be entitled to convert into our common stock at the Alternate Conversion Price.

In the event that we experience

a “Change of Control” (as defined in the Certificate of Designations) we may also be required to redeem the Series A Preferred

Stock for cash at a minimum of 125% of their Conversion Amount.

In addition, if thirty days after our common stock commences trading on

Nasdaq the sum of the average daily dollar volume for the 10 days previous to conversion divided by 10 is less than $2,500,000, then the

Series A Preferred Stock shall be entitled to a one-time dividend equal to an 8% increase in the stated value of the Series A Preferred

Stock, or an $80 increase per share in stated value, resulting in a stated value of $1,080 per share of Series A Preferred Stock.

dividend was paid during the first quarter of 2022.

The Certificate of Designations of Series A Convertible Preferred Stock of Allarity

Therapeutics, Inc.

was filed as Exhibit 3.4 to the Company’s Registration Statement on Form S-1, as amended, filed with the SEC

on September 13, 2021.

On May 4, 2022, the Company

and the Investor entered into a Forbearance Agreement and Waiver, dated April 27, 2022, wherein the Investor confirmed that no Triggering

Event as defined under the Certificate of Designations has occurred prior to April 27, 2022, that a Triggering Event under Section 5(a)(ii)

will and has occurred on April 29, 2022, and that in consideration for the Registration Delay Payments the Company is obligated to pay

under the RRA, and additional amounts the Company is obligated to pay under the Certificate of Designations and the Investor’s legal

fees incurred in the preparation of the Forbearance Agreement and Waiver in the aggregate of $538,823 paid upon execution of the Forbearance

Agreement and Waiver, and so long as the Company pays the Registration Delay Payments that become due and payable under the RRA after

the execution of the Forbearance Agreement and Waiver, the Investor has agreed to forbear exercising any rights or remedies that it may

have under the Certificate of Designations that arises as a result of a Triggering Event under Section 5(a)(ii) of the Certificate of

Designations and Section 4(c)(ii) of the PIPE Warrant until the earlier to occur of (i) the date immediately prior to the date of occurrence

of a Bankruptcy Triggering Event, (ii) the date of occurrence of any other Triggering Event under Section 5(a) of the Certificate of Designations

(excluding any Triggering Event arising solely as a result of Section 5(a)(ii) of the Certificate of Designations and Section 4(c)(ii)

of the PIPE Warrant), (iii) the time of any breach by the Company under the Forbearance Agreement and Waiver, (iv) the Resale Availability

Date as defined therein and (v) June 4, 2022, which was subsequently extended to June 20, 2022 (such period, the “Forbearance Period”).

Provided that the Company is not in breach of its obligations under Forbearance Agreement and Waiver, effective as of the Trading Day

immediately following the Resale Availability Date, the Investor agrees to waive any rights or remedies that it may have under the Certificate

of Designations that arises as a result of a Triggering Event under Section 5(a) of the Certificate of Designations and Section 4(c)(ii)

of the PIPE Warrant that may have arisen prior to the date of the Forbearance Agreement and Waiver.

The Resale Availability Date was achieved

on June 6, 2022, resulting in the Investor waiving any rights or remedies that it may have under the Certificate of Designations that

arises as a result of a Triggering Event under Section 5(a) of the Certificate of Designations and Section 4(c)(ii) of the PIPE Warrant

that may have arisen prior to the date of the Forbearance Agreement and Waiver.

On June 6, 2022, we entered

into that certain First Amendment to the Forbearance Agreement and Waiver with 3i, LP (the “Amendment”) to extend the forbearance

period date under subsection 5 of Section 2 of the Forbearance Agreement and Waiver dated April 27, 2022 (the “Original Agreement”)

from June 4, 2022, to June 20, 2022.

In addition, the parties agreed that the forbearance period of June 20, 2022 may also be extended

for an additional fifteen (15) days to July 5, 2022, provided that, on June 20, 2022 the Company will remove the restrictive legend on

441,005 shares of common stock of the Company issued in connection with the conversion of certain shares of Series A Preferred Stock (“Conversion

Shares”) by 3i, LP pursuant to the conversion notice dated May 2, 2022, and 3i, LP is able to sell the Conversion Shares free

of restrictions (including volume restrictions) pursuant to SEC Rule 144(b)(1)(i).

Simultaneously

with the closing of its Recapitalization Share Exchange, we closed on the PIPE Investment pursuant to the SPA.

On December 20, 2021,

we issued 20,000 shares of Series A Preferred Stock at $1,000 per share and a common stock purchase warrant to purchase 2,018,958 shares

of common stock at an initial exercise price of $9.9061 to the Investor for an aggregate purchase price of $20 million.

Each share of

Series A Preferred Stock has a right to convert into shares of our common stock at an initial fixed conversion price of $9.9061.

if (i) the price of our shares of common stock trade below $9.9061 (a “Price Failure”) for a specified period of time;

(ii) in the event that the sum of (x) the aggregate daily dollar trading volume (as reported on Bloomberg) of our common stock on Nasdaq

during the 10 trading day period ending on the trading day immediately preceding such date of determination, divided by (y) 10, is less

than $1,500,000 (a “Volume Maximum Failure”), each share of Series A Preferred Stock is entitled to convert at a price equal

to 90% of the sum of the two lowest VWAPs during the 10 trading day period immediately preceding delivery divided by two (the “90%

Conversion Price”), but not less than the Floor Price, or, at the time of such Price Failure or Volume Maximum Failure, the sum

of the average daily U.S.

Dollar volume for our common stock during the 10 days previous to conversion divided by 10 is less than $2,000,000

(a “Volume Alternate Failure”), then each share of Series A Preferred Stock is entitled to convert at the lower of the fixed

conversion price or a price equal to 80% of the sum of the two lowest VWAPs during the 10 trading day period immediately preceding delivery

divided by two (the “80% Conversion Price”), but not less than the Floor Price (such 90% Conversion Price or 80% Conversion

Price, as the case may be, the “Alternate Conversion Price”).

If certain defined “Triggering Events” defined

in the Certificate of Designations occur, such as a breach of the Registration Rights Agreement, suspension of trading, or our failure

to convert the Series A Preferred Stock into common stock when a conversion right is exercised, failure to issue our common stock when

the PIPE Warrant is exercised, failure to declare and pay to any holder any dividend on any dividend date, certain defaults on our debts

or contractual obligations, or upon a “bankruptcy triggering event” (as defined in the Certificate of Designations), then

we may be required to pay a dividend that is added to the stated value on the Series A Preferred Stock in the amount of 18% per annum,

but paid quarterly in cash, so long as the triggering event is continuing, or to redeem the Series A Preferred Stock for cash in an amount

of a minimum of 125% of the Conversion Amount (as defined in the Certificate of Designations) of the Series A Preferred Stock or 125%

of the Conversion Amount of the Series A Preferred Stock would be entitled to convert into our common stock at the Alternate Conversion

In the event that we experience a “Change of Control” (as defined in the Certificate of Designations) we may also

be required to redeem the Series A Preferred Stock for cash at a minimum of 125% of their Conversion Amount.

In addition, if thirty days

after our common stock commences trading on Nasdaq the sum of the average daily dollar volume for the 10 days previous to conversion

divided by 10 is less than $2,500,000, then the Series A Preferred Stock shall be entitled to a one-time dividend equal to an 8% increase

in the stated value of the Series A Preferred Stock, or an $80 increase per share in stated value, resulting in a stated value of $1,080

per share of Series A Preferred Stock.

This dividend was paid during the first quarter of 2022.

The Certificate of Designations of Series

A Convertible Preferred Stock of Allarity Therapeutics, Inc.

was filed as Exhibit 3.4 to the Company’s Registration Statement on

Form S-1, as amended, filed with the SEC on September 13, 2021.

May 4, 2022, the Company and the Investor entered into a Forbearance Agreement and Waiver, dated April 27, 2022, wherein the Investor

confirmed that no Triggering Event as defined under the Certificate of Designations has occurred prior to April 27, 2022, that a Triggering

Event under Section 5(a)(ii) will and has occurred on April 29, 2022, and that in consideration for the Registration Delay Payments the

Company is obligated to pay under the RRA, and additional amounts the Company is obligated to pay under the Certificate of Designations

and the Investor’s legal fees incurred in the preparation of the Forbearance Agreement and Waiver in the aggregate of $538,823

paid upon execution of the Forbearance Agreement and Waiver, and so long as the Company pays the Registration Delay Payments that become

due and payable under the RRA after the execution of the Forbearance Agreement and Waiver, the Investor has agreed to forbear exercising

any rights or remedies that it may have under the Certificate of Designations that arises as a result of a Triggering Event under Section

5(a)(ii) of the Certificate of Designations and Section 4(c)(ii) of the PIPE Warrant until the earlier to occur of (i) the date immediately

prior to the date of occurrence of a Bankruptcy Triggering Event, (ii) the date of occurrence of any other Triggering Event under Section

5(a) of the Certificate of Designations (excluding any Triggering Event arising solely as a result of Section 5(a)(ii) of the Certificate

of Designations and Section 4(c)(ii) of the PIPE Warrant), (iii) the time of any breach by the Company under the Forbearance Agreement

and Waiver, (iv) the Resale Availability Date as defined therein and (v) June 4, 2022, which was subsequently extended to June 20, 2022

(such period, the “Forbearance Period”).

Provided that the Company is not in breach of its obligations under Forbearance

Agreement and Waiver, effective as of the Trading Day immediately following the Resale Availability Date, the Investor agrees to waive

any rights or remedies that it may have under the Certificate of Designations that arises as a result of a Triggering Event under Section

5(a) of the Certificate of Designations and Section 4(c)(ii) of the PIPE Warrant that may have arisen prior to the date of the Forbearance

Agreement and Waiver.

The Resale Availability Date was achieved on June 6, 2022, resulting in the Investor waiving any rights or remedies

that it may have under the Certificate of Designations that arises as a result of a Triggering Event under Section 5(a) of the Certificate

of Designations and Section 4(c)(ii) of the PIPE Warrant that may have arisen prior to the date of the Forbearance Agreement and Waiver.

June 6, 2022, we entered into that certain First Amendment to the Forbearance Agreement and Waiver with 3i, LP (the “Amendment”)

to extend the forbearance period date under subsection 5 of Section 2 of the Forbearance Agreement and Waiver dated April 27, 2022 (the

“Original Agreement”) from June 4, 2022, to June 20, 2022.

In addition, the parties agreed that the forbearance period

of June 20, 2022 may also be extended for an additional 15 days to July 5, 2022, provided that, on June 20, 2022 the Company will remove

the restrictive legend on 441,005 shares of common stock of the Company issued in connection with the conversion of certain shares of

Series A Preferred Stock (“Conversion Shares”) by 3i, LP pursuant to the conversion notice dated May 2, 2022, and 3i,

LP is able to sell the Conversion Shares free of restrictions (including volume restrictions) pursuant to SEC Rule 144(b)(1)(i).

December 9, 2022, the Company and 3i, LP entered into a letter agreement which provided that pursuant to Section 8(g) of the Certificate

5 unchanged sentences

through and until the Company and 3i agree to terminate that definition.

January 14, 2024, pursuant to the terms of the January 14th, 2024, 3i, LP Bridge Loan, the Company modified the conversion price of the

3i Exchange Warrants from $1.00 to $0.4476, thereby increasing the number of Exchange Warrants outstanding from 4,407,221 at December

31, 2023, to 9,846,339 outstanding at January 14, 2024.

Also on January 14, 2024, the conversion price of the outstanding 1,417 shares

of Series A Preferred Stock was revised from $1.00 to $0.4476.

We filed the Fifth Certificate of Amendment to Amended and Restated Certificate

of Designations of Series A Convertible Preferred Stock (the “Fifth Amendment”) with the Secretary of State of the State

of Delaware to reflect the new conversion price of the Series A Preferred Stock of $0.4476.

At a stated value of $1,080 for each share

of Series A Preferred Stock, the revised price of $0.4476 per share results in the 1,417 shares being convertible into 3,419,035 common

shares as of January 14, 2024.

February 13, 2024, pursuant to the terms of the February 13, 2024, 3i, LP Bridge Loan, the Company modified the conversion price of the

3i Exchange Warrants from $0.4476 to $0.4050 and thereby increased the number of Exchange Warrants outstanding from 9,846,339 on January

18, 2024, to 10,882,028 on February 13, 2024.

The Company also agreed to amend the conversion price of the Series A Preferred Stock to

equal $0.405 as soon as practicable.

We filed the Sixth Certificate of Amendment to Amended and Restated Certificate of Designations

of Series A Convertible Preferred Stock (the “Sixth Amendment”) with the Secretary of State of the State of Delaware to reflect

the new conversion price of the Series A Preferred Stock of $0.405.

At a stated value of $1,080 for each share of Series A Preferred

Stock, the revised price of $0.405 per share results in the 1,296 shares being convertible into 3,456,000 common shares.

November 22, 2022, the Company entered into a Secured Note Purchase Agreement with 3i, LP (the “Secured Note Purchase Agreement”)

8 unchanged sentences

Designations, that began to accrue on July 14, 2022;

and the third note in an aggregate principal amount of $650,000 with respect to a

new loan to be funded upon the Company filing a registration statement with SEC in connection with a registered offering.

and the third note in an aggregate principal amount of $650,000 with respect to

a new loan to be funded upon the Company filing a registration statement with SEC in connection with a registered offering.

As of December

4 unchanged sentences

exchange the 3i Promissory Notes for the Company’s common stock, or other equity security, at an exchange price equal to the lowest

price per share of the equity security sold to other purchasers, rounded down to the nearest whole share, if the Company concludes a future

equity financing prior to the maturity date or other repayment of the 3i Promissory Notes.

In addition, each 3i Promissory Note and interest

earned thereon may be redeemed by the Company at its option or the holder may demand redemption if the Company obtains gross proceeds

of at least $5 million in a financing in an amount of up to 35% of the gross proceeds of the financing.

Amendment to the Certificate of Designation of Series A Preferred

On November 22, 2022, the

Company amended Section 12 of the Certificate of Designation of Series A Preferred Stock to provide for voting rights.

Subject to a 9.99%

beneficial ownership limitation, the holders of Series A Preferred Stock were granted the right to vote on all matters presented to the

stockholders for approval together with the shares of common stock, voting together as a single class, on an “as converted”

basis using the “Conversion Price” (initially $9.9061 per share before any adjustment) (rounded down to the nearest whole

number and using the record date for determining the stockholders of the Company eligible to vote on such matters), except as required

by law (including without limitation, the DGCL) or as otherwise expressly provided in the Company’s Certificate of Incorporation

or the Certificate of Designations of Series A Preferred Stock.

price per share of the equity security sold to other purchasers, rounded down to the nearest whole share, if the Company concludes a

future equity financing prior to the maturity date or other repayment of the 3i Promissory Notes.

In addition, each 3i Promissory Note

and interest earned thereon may be redeemed by the Company at its option or the holder may demand redemption if the Company obtains gross

proceeds of at least $5 million in a financing in an amount of up to 35% of the gross proceeds of the financing.

April 19, 2023, 3i, provided the Company with a loan for $350,000, which was evidenced by a Secured Promissory Note dated April 19, 2023

(the “April Note”).

April 20, 2023, the Company entered into a Cancellation of Debt Agreement with 3i, which became effective as of the April Offering Closing.

Upon the closing, pursuant to the terms of the Cancellation of Debt Agreement, all of the Company’s outstanding indebtedness under

the Notes (as defined therein) and the Alternative Conversion Amount (as defined therein) due by the Company to 3i were paid in full.

Accordingly, any and all obligations in connection therewith were extinguished without any additional further action on the part of 3i

upon payment of $3,348 in cash from a portion of the proceeds from the April Offering.

June 29, 2023, the Company entered into a Secured Note Purchase Agreement with 3i, (the “June 2023 Purchase Agreement”),

pursuant to which, on June 30, 2023, 3i purchased a secured promissory note for a principal amount of $350,000 (the “3i June Promissory

Such note matured on July 31, 2023, and carried an interest rate of 5% per annum, and is secured by all of the Company’s

assets pursuant to that certain security agreement dated June 29, 2023 (the “Security Agreement”).

As contemplated by

the June 2023 Purchase Agreement, the Company filed the Second Certificate of Amendment with the Delaware Secretary of State on June

From the proceeds of the July Offering, on July 10, 2023, the Company redeemed the 3i June Promissory Note for $351,000 in

January 18th, 2024, we entered into a Securities Purchase Agreement with 3i, pursuant to which we issued and sold 3i a senior convertible

promissory notes in an aggregate principal amount of $440,000 due on January 18, 2025 (the “First Note”, and together with

the Purchase Agreement, the “Transaction Documents”) for an aggregate purchase price of $400,000, representing an approximate

10% original issue discount (the “Transaction”).

We agreed to use the net proceeds from the sale of the Note for accounts

payable and working capital purposes.

Unless the Transaction Documents state otherwise, we may not prepay any portion of the principal

amount of the Note without the Purchaser’s prior written consent.

February 13, 2024 (the “Second Closing”), the Parties entered into a Limited Waiver Agreement (the “Waiver Agreement”)

and agreed that the Second Closing can be consummated prior to the 30th calendar day following January 18, 2024.

The Parties further

waive any rights or remedies that they may have under Section 2.3 of the Purchase Agreement, solely in connection with the Second Closing,

including any rights of termination, defaults, amendment, acceleration or cancellation that be triggered under the Purchase Agreement

solely as a result of accelerating the Second Closing.

As of the Second Closing, we issued and sold to the Purchaser a senior convertible

promissory note in an aggregate principal amount of $440,000 (the “Principal Amount”) due on February 13, 2025 (the “Second

Note,” and together with the First Note dated January 18, 2024, and Purchase Agreement, the “Second Transaction Documents”)

for an aggregate purchase price of $400,000, representing an approximately 10% original issue discount (the “Second Transaction”).

We agreed to use the net proceeds from the sale of the Second Note for accounts payable and working capital purposes.

Unless the Transaction

Documents state otherwise, we may not prepay any portion of the principal amount of the Second Note without the Purchaser’s prior

written consent.

to the Certificate of Designation of Series A Preferred Stock

November 22, 2022, the Company amended Section 12 of the Certificate of Designation of Series A Preferred Stock to provide for voting

Subject to a 9.99% beneficial ownership limitation, the holders of Series A Preferred Stock were granted the right to vote on

all matters presented to the stockholders for approval together with the shares of common stock, voting together as a single class, on

an “as converted” basis using the “Conversion Price” (initially $9.9061 per share before any adjustment) (rounded

down to the nearest whole number and using the record date for determining the stockholders of the Company eligible to vote on such matters),

except as required by law (including without limitation, the DGCL) or as otherwise expressly provided in the Company’s Certificate

of Incorporation or the Certificate of Designations of Series A Preferred Stock.

The voting rights described above expired on February

Modification to Conversion Price of Series

A Preferred Stock

December 9, 2022, the Company and 3i entered into a letter agreement which provided that pursuant to Section 8(g) of the Certificate

of Designations for the Series A Preferred Stock, the parties agreed that the Conversion Price was modified to mean the lower of:

the Closing Sale Price on the trading date immediately preceding the Conversion Date and (ii) the average Closing Sale Price of the common

stock for the five trading days immediately preceding the Conversion Date, for the Trading Days through and inclusive of January 19,

Any conversion which occurs shall be voluntary at the election of the Holder, which shall evidence its election as to the Series

A being converted in writing on a conversion notice setting forth the then Minimum Price.

Management determined that the adjustment made

to the Conversion Price is not a modification of the COD which allows for adjustments to the Conversion Price at any time by the Company

and the other terms of the Certificate of Designations remained unchanged.

January 23, 2023, we and 3i amended the letter agreement entered into on December 8, 2022, to provide that the modification of the term

Series A Preferred Stock Conversion Price (“Series A Preferred Stock Conversion Price”) to mean the lower of:

(i) the Closing

Sale Price (as defined in the Certificate of Designations of Series A Preferred Stock (“Series A Certificate of Designations”))

on the trading date immediately preceding the Conversion Date (as defined in the Series A Certificate of Designations and (ii) the average

Closing Sale Price of the common stock for the five trading days immediately preceding the Conversion Date, for the Trading Days (as

defined in the Series A Certificate of Designations) will be in effect until terminated by us and 3i.

April 20, 2023, the Company entered into a certain Modification and Exchange Agreement (the “Exchange Agreement”) with 3i

pursuant to which the parties agreed to, among other things, subject to the April Offering Closing, (i) amend the Certificate of Designations

for the Series A Convertible Preferred Stock (the “Amended COD”), which among other things, eliminates the Series A Preferred

Stock redemption right and dividend (except for certain exceptions as specified in the Amended COD), and provides for the conversion

of Series A Preferred Stock into Common Stock at a conversion price of $0.75 which is equal to the price for a share of Common Stock

sold in the April Offering, (ii) exchange 50,000 shares of Series C Preferred Stock (the “Series C Shares”) beneficially

owned by 3i for 5,577 shares of Series A Preferred Stock (the “Exchange Shares”), (iii) exchange a warrant to purchase common

stock issued on December 20, 2021 to 3i (the “Original Warrant”) for a new warrant (the “Exchange Warrant”),

which reflects an exercise price of $30.00 (the “New Exercise Price”) and represents a right to acquire 315,085 shares of

Common Stock (the “New Warrant Shares”).

addition to the satisfaction or waiver of customary and additional closing conditions set forth in the Exchange Agreement, the transactions

contemplated by the Exchange Agreement were subject to (a) the occurrence of the closing of the Offering and (b) the filing of the Amended

COD with the Delaware Secretary of State.

On April 21, 2023, the closing of the transactions contemplated by the Exchange Agreement occurred

and the Exchange Warrant and the Exchange Shares were issued to 3i, and the Original Warrant and the Series C Shares were cancelled.

In addition, on April 21, 2023, the Amended COD was filed with the Delaware Secretary of State.

April 20, 2023, the Company also entered into a Cancellation of Debt Agreement.

Pursuant to such agreement, 1,550 shares of Series A

Preferred Stock (the “Redemption Shares”) beneficially owned by 3i were redeemed in full for a purchase price of $1,652,

which redemption price was paid in cash from the portion of the proceeds from the April Offering.

The Company also entered into the First

Amendment to the Registration Rights Agreement dated May 20, 2023 (the “RRA”), which became effective upon the April Offering

Closing, to amend certain defined terms under the RRA to include the Exchange Shares, the New Warrant Shares and the Note Conversion

April 21, 2023, in connection with the transactions contemplated under the Exchange Agreement, the Company filed an Amended and Restated

Certificate of Designations of Series A Convertible Preferred Stock of the Company (the “Amended and Restated Series A COD”) with

the Delaware Secretary of State.

The Amended and Restated Series A COD eliminates the Series A Preferred Stock redemption right

and dividend (except for certain exceptions as specified therein), and provides for the conversion of Series A Preferred Stock into Common

Stock at a conversion price equal to the price for a share of Common Stock sold in the April Offering, $30.00 per share, and based on

a stated value of $1,080 per share.

As a result of the Amended and Restated Series A COD, the Company determined that the Series A Preferred

Stock met the definition of equity and reclassified it from mezzanine equity.

May 30, 2023, the Company filed an amendment to the Amended and Restated Certificate of Designations for the Series A Preferred Stock

with the Delaware Secretary of State (the “Amended COD”) to amend the voting rights of the Series A Preferred Stock which

among other things provided additional voting rights to the Series A Preferred Stock.

the Amended COD, holders of the Series A Preferred Stock have the following voting rights:

(1) holders of the Series A Preferred Stock

have a right to vote on all matters presented at the Special Meeting together with the Common Stock as a single class on an “as

converted” basis using the conversion price of $30.00 and based on stated value of $1,080 subject to a beneficial ownership limitation

of 9.99%, and (2), in addition, holders of Series A Preferred Stock have granted the Board the right to vote, solely for the purpose

of satisfying quorum and casting the votes necessary to adopt a reverse stock split of the Company’s issued and outstanding shares

of Common Stock (the “Reverse Stock Split Proposal”) and to adjourn any meeting of stockholders called for the purpose of

voting on reverse stock split (the “Adjournment Proposal”) under Delaware law, that will “mirror” the votes cast

by the holders of shares of Common Stock and Series A Preferred Stock, voting together as a single class, with respect to the Reverse

Stock Split Proposal and the Adjournment Proposal.

The number of votes per each share of Series A Preferred Stock that may be voted by

the Board shall be equal to the quotient of (x) the sum of (1) the original aggregated stated value of the Series A Preferred Stock when

originally issued on December 20, 2021 (calculated based on the original stated value of $1,000 of the Series A Preferred Stock multiplied

by 20,000 shares of Series A Preferred Stock) and (2) $1,200,000, which represents the purchase price of the Series C Preferred Stock

when originally issued;

divided by (y) the conversion price of $30.00.

If the Board decides to cast the vote, it must vote all votes

created by the Amended COD in the same manner and proportion as votes cast by the holders of Common Stock and Series A Preferred Stock,

voting as single class.

The Series A Preferred Stock voting rights granted to the holders thereof relating to the Reverse Stock Split

Proposal and the Adjournment Proposal 2 expired automatically on July 31, 2023.

June 6, 2023, 3i and the Company entered into a separate limited waiver and amendment agreement whereby 3i (“3i Waiver Agreement”)

agreed to waive certain rights granted under a Series A Preferred Stock securities purchase agreement dated December 20, 2021, the Exchange

Agreement, and the securities purchase agreement related to the April Offering in exchange for, among other things, amending the conversion

price of the Series A Preferred Stock to equal the public offering price of the shares of Common Stock in the July Offering.

consummation of the July Offering, the conversion price of the Series A Preferred Stock was reduced to $4.50.

On July 10, 2023, the Company

filed a Third Certificate of Amendment to the Amended and Restated Certificate of Designations of Series A Preferred Stock (“Third

Amendment”) to effect the change to conversion price.

connection with the September 2023 Inducement Letter and the transactions contemplated therein, the Company and 3i, LP entered into a

limited waiver agreement (the “Waiver”) pursuant to which 3i, LP agreed to allow the filing of the Resale Registration Statement

not otherwise permitted under certain agreements with 3i, LP.

In consideration of entering in the Waiver, the Company agreed to amend

the “Conversion Price” of the Series A Convertible Preferred Stock to equal $1.00 as soon as practicable.

On September 22,

2023, the Company filed the Fourth Certificate of Amendment to the Amended and Restated Certificate of Designations of Series A Convertible

Preferred Stock (“Fourth Amendment”) with the Secretary of State of the State of Delaware to reflect the new conversion price

of the Series A Preferred Stock of $1.00.

In addition, as a result of the issuance of the Inducement Warrants, pursuant to the terms

of the Exchange Warrant, in September 2023 the number of shares exercisable and the exercise price of the Exchange Warrant was adjusted

to 9,452,667 shares of Common Stock and $1.00 per share, respectively.

January 14, 2024, pursuant to the terms of the January 14th, 2024, 3i, LP Bridge Loan, the Company modified the conversion price of the

3i Exchange Warrants from $1.00 to $0.4476, thereby increasing the number of Exchange Warrants outstanding from 4,407,221 at December

31, 2023, to 9,846,339 outstanding at January 14, 2024.

Also on January 14, 2024, the conversion price of the outstanding 1,417 shares

of Series A Preferred Stock was revised from $1.00 to $0.4476.

We filed the Fifth Amendment with the Secretary of State of the State

of Delaware to reflect the new conversion price of the Series A Preferred Stock of $0.4476.

At a stated value of $1,080 for each share

of Series A Preferred Stock, the revised price of $0.4476 per share results in the 1,417 shares being convertible into 3,419,035 common

shares as of January 14, 2024.

February 13, 2024, pursuant to the terms of the February 13, 2024, 3i, LP Bridge Loan, the Company modified the conversion price of the

3i Exchange Warrants from $0.4476 to $0.4050 and thereby increased the number of Exchange Warrants outstanding from 9,846,339 on January

18, 2024, to 10,882,028 on February 13, 2024.

The Company also agreed to amend the conversion price of the Series A Preferred Stock to

equal $0.405 as soon as practicable.

We filed the Sixth Amendment with the Secretary of State of the State of Delaware to reflect the

new conversion price of the Series A Preferred Stock of $0.405.

At a stated value of $1,080 for each share of Series A Preferred Stock,

the revised price of $0.405 per share results in the 1,296 shares being convertible into 3,456,000 common shares.

Modifications

to Conversion Price of Series A Preferred Stock

December 9, 2022, the Company and 3i, LP, the holder of outstanding shares of Series A Preferred Stock, entered into a letter agreement

1 unchanged sentence

in such Certificate of Designations) was modified to mean the lower of:

(i) the Closing Sale Price (as defined in the Certificate of Designations)

on the trading date immediately preceding the Conversion Date (as defined in the Certificate of Designations) and (ii) the average Closing

Sale Price of the common stock for the five trading days immediately preceding the Conversion Date, for the Trading Days (as defined in

the Certificate of Designations) through and inclusive of January 19, 2023.

On January 23, 2023, the Company and 3i, LP amended

the Letter Agreement to provide the term Conversion Price will be in effect until terminated by the Company and 3i, LP.

Establishment of Series B Preferred Stock

On November 22, 2022, the

Company’s Board of Directors established the Series B Preferred Stock, par value $0.0001 per share (“Series B Preferred Stock”).

Each share of Series B Preferred Stock has 400 votes and is subject to certain redemption rights and voting limitations.

See description

in exhibit titled “ Description of Capital Stock – Series B Preferred Stock.

Issuance of Series B Preferred Stock Dividend

Effective December 5, 2022,

the Company issued a stock dividend to be distributed as follows to stockholders of record as of close of business on December 5, 2022:

(i) the Closing Sale Price (as defined in the Certificate of

Designations) on the trading date immediately preceding the Conversion Date (as defined in the Certificate of Designations) and (ii)

the average Closing Sale Price of the common stock for the five trading days immediately preceding the Conversion Date, for the Trading

Days (as defined in the Certificate of Designations) through and inclusive of January 19, 2023.

On January 23, 2023, the

Company and 3i, LP amended the Letter Agreement to provide the term Conversion Price will be in effect until terminated by the Company

Establishment

of Series B Preferred Stock

November 22, 2022, the Company’s Board of Directors established the Series B Preferred Stock, par value $0.0001 per share (“Series

B Preferred Stock”).

Each share of Series B Preferred Stock has 400 votes and is subject to certain redemption rights and voting

See description in exhibit titled “ Description of Capital Stock – Series B Preferred Stock.

Series B Preferred Stock Dividend

December 5, 2022, the Company issued a stock dividend to be distributed as follows to stockholders of record as of close of business

on December 5, 2022:

(i) 0.016 shares of Series B Preferred Stock for each outstanding share of common stock;

and (ii) 1.744 shares of Series B Preferred Stock

for each outstanding share of Series A Preferred Stock.

An aggregate of 190,786 shares of Series B Preferred Stock were issued as a stock

Annual Stockholder Meeting and Redemption of

Series B Preferred Stock

On February 3, 2023, we held

our previously adjourned annual meeting of stockholders (the “Annual Meeting”).

Nine proposals were submitted to our stockholders

for a vote at the Annual Meeting including a proposal to increase the number of authorized shares and a proposal to effect a reverse stock

Upon conclusion of the Annual Meeting, all of the 190,786 shares of Series B Preferred Stock were automatically redeemed, with

the holders of the Series B Preferred Stock only having a right to receive the purchase price for the redemption, which was $0.01 per

share of Series B Preferred Stock.

In addition, the proposals to increase the number of authorized shares and to effect a reverse stock

split did not pass by the requisite shareholder vote at the Annual Meeting.

In light of our financing needs and our obligations to 3i,

L.P., as holder of the Series A Preferred Stock and PIPE Warrant, we conducted a private placement offering pursuant to which we issued

50,000 shares of Series C Preferred Stock.

Establishment of Series C Preferred Stock and

Sale of Series C Preferred Stock

On February 24, 2023, the

Company filed a Certificate of Designation of Preferences, Rights and Limitations of Series C Convertible Redeemable Preferred Stock (the

“Series C COD”) with the Delaware Secretary of State designating 50,000 shares of its authorized and unissued preferred stock

as Series C Preferred Stock with a stated value of $27.00 per share.

On February 28, 2023, the Company filed a Certificate of Amendment

to the Series C COD (the “COD Amendment”) to clarify the terms of conversion price and floor price based on definitions provided

in the Series C COD (the COD Amendment, together with the Series C COD, the “COD”).

Each share of Series B Preferred Stock

has 620 votes and is subject to certain redemption rights and voting limitations.

See description in exhibit titled “ Description

of Capital Stock - Series C Preferred Stock.

On February 28, 2023, we entered

into a Securities Purchase Agreement (the “SPA”) with 3i, L.P.

for the purchase and sale of 50,000 shares of Series C Convertible

Redeemable Preferred Stock, par value of $0.0001 per share of Series C Preferred Stock at a purchase price of $24.00 per share, for a

subscription receivable in the aggregate amount equal to the total purchase price of $1.2 million (the “Series C Offering”).

The Shares are convertible into shares of the Company’s common stock, subject to the terms of the COD.

The conversion price for

the Series C Preferred Stock is initially equal the lower of:

(i) $0.182, which is the official closing price of the Common Stock on the

Nasdaq Global Market (as reflected on Nasdaq.com) on the Trading Day (as defined in the COD) immediately preceding the Original Issuance

Date (as defined in the COD);

and (ii) 1.744 shares of

Series B Preferred Stock for each outstanding share of Series A Preferred Stock.

An aggregate of 190,786 shares of Series B Preferred

Stock were issued as a stock dividend.

Stockholder Meeting and Redemption of Series B Preferred Stock

February 3, 2023, we held our previously adjourned annual meeting of stockholders (the “Annual Meeting”).

Nine proposals

were submitted to our stockholders for a vote at the Annual Meeting including a proposal to increase the number of authorized shares

and a proposal to effect a reverse stock split.

Upon conclusion of the Annual Meeting, all of the 190,786 shares of Series B Preferred

Stock were automatically redeemed, with the holders of the Series B Preferred Stock only having a right to receive the purchase price

for the redemption, which was $0.01 per share of Series B Preferred Stock.

In addition, the proposals to increase the number of authorized

shares and to effect a reverse stock split did not pass by the requisite shareholder vote at the Annual Meeting.

In light of our financing

needs and our obligations to 3i, L.P., as holder of the Series A Preferred Stock and PIPE Warrant, we conducted a private placement offering

pursuant to which we issued 50,000 shares of Series C Preferred Stock.

Establishment

of Series C Preferred Stock and Sale of Series C Preferred Stock

February 24, 2023, the Company filed a Certificate of Designation of Preferences, Rights and Limitations of Series C Convertible Redeemable

Preferred Stock (the “Series C COD”) with the Delaware Secretary of State designating 50,000 shares of its authorized and

unissued preferred stock as Series C Preferred Stock with a stated value of $27.00 per share.

On February 28, 2023, the Company filed

a Certificate of Amendment to the Series C COD (the “COD Amendment”) to clarify the terms of conversion price and floor price

based on definitions provided in the Series C COD (the COD Amendment, together with the Series C COD, the “COD”).

of Series B Preferred Stock has 620 votes and is subject to certain redemption rights and voting limitations.

See description in exhibit

titled “ Description of Capital Stock - Series C Preferred Stock.

February 28, 2023, we entered into a SPA with 3i, L.P.

for the purchase and sale of 50,000 shares of Series C Convertible Redeemable

Preferred Stock, par value of $0.0001 per share of Series C Preferred Stock at a purchase price of $24.00 per share, for a subscription

receivable in the aggregate amount equal to the total purchase price of $1.2 million (the “Series C Offering”).

are convertible into shares of the Company’s common stock, subject to the terms of the COD.

The conversion price for the Series

C Preferred Stock is initially equal the lower of:

(i) $0.182, which is the official closing price of the Common Stock on the Nasdaq

Global Market (as reflected on Nasdaq.com) on the Trading Day (as defined in the COD) immediately preceding the Original Issuance Date

(as defined in the COD);

and (ii) the lower of:

(x) the official closing price of the Common Stock on the Nasdaq Global Market (as

reflected on Nasdaq.com) on the Trading Day immediately preceding the Conversion Date or such other date of determination;

average of the official closing prices of the Common Stock on the Nasdaq Global Market (as reflected on Nasdaq.com) for the five (5) Trading

Days immediately preceding the Conversion Date (as defined in the COD) or such other date of determination, subject to adjustment herein

(the “Conversion Price”), with the Conversion Price being no less than $0.0370 (the “Floor Price”).

that the Conversion Price on a Conversion Date would have been less than the applicable Floor Price if not for the immediately preceding

sentence, then on any such Conversion Date the Company will pay the Holder an amount in cash, to be delivered by wire transfer out of

funds legally and immediately available therefor pursuant to wire instructions delivered to the Company by the Holder in writing, equal

to the product obtained by multiplying (A) the higher of (I) the highest price that the Common Stock trades at on the Trading Day immediately

preceding such Conversion Date and (II) the applicable Conversion Price and (B) the difference obtained by subtracting (I) the number

of shares of Common Stock delivered (or to be delivered) to the Holder on the applicable Share Delivery Date with respect to such conversion

of Series C Preferred Stock from (II) the quotient obtained by dividing (x) the applicable Conversion Amount that the Holder has elected

(x) the official closing price of the Common Stock on the Nasdaq Global Market (as reflected

on Nasdaq.com) on the Trading Day immediately preceding the Conversion Date or such other date of determination;

and (y) the average

of the official closing prices of the Common Stock on the Nasdaq Global Market (as reflected on Nasdaq.com) for the 5 Trading Days immediately

preceding the Conversion Date (as defined in the COD) or such other date of determination, subject to adjustment herein (the “Conversion

Price”), with the Conversion Price being no less than $0.0370 (the “Floor Price”).

In the event that the Conversion

Price on a Conversion Date would have been less than the applicable Floor Price if not for the immediately preceding sentence, then on

any such Conversion Date the Company will pay the Holder an amount in cash, to be delivered by wire transfer out of funds legally and

immediately available therefor pursuant to wire instructions delivered to the Company by the Holder in writing, equal to the product

obtained by multiplying (A) the higher of (I) the highest price that the Common Stock trades at on the Trading Day immediately preceding

such Conversion Date and (II) the applicable Conversion Price and (B) the difference obtained by subtracting (I) the number of shares

of Common Stock delivered (or to be delivered) to the Holder on the applicable Share Delivery Date with respect to such conversion of

Series C Preferred Stock from (II) the quotient obtained by dividing (x) the applicable Conversion Amount that the Holder has elected

to be the subject of the applicable conversion of Series C Preferred Stock, by (y) the applicable Conversion Price without giving effect

1 unchanged sentence

The Offering closed on February 28, 2023.

In connection with the Series

C Offering, concurrently with the SPA, the Company entered into a registration rights agreement with 3i, L.P.

pursuant to which the Company is required to file a registration statement with the SEC to register for resale the shares of Common Stock

that are issued upon the potential conversion of the Shares.

Under the terms of the RRA, if we fail file an Initial Registration Statement

(as defined in the RRA) on or prior to its Filing Date (as defined in the RRA), or fail to maintain the effectiveness of the registration

statement beyond defined allowable grace periods set forth in the RRA, we will incur certain registration delay payments, in cash and

as partial liquidated damages and not as a penalty, equal to 2.0% of 3i, L.P.’s subscription amount of the Shares pursuant to the

In addition, if we fail to pay any partial liquidated damages in full within seven (7) days after the date payment, we will have

to pay interest at a rate of 18.0% per annum, accruing daily from the date such partial liquidated damages are due until such amounts,

plus all such interest thereon, are paid in full.

The Company has also agreed to pay all fees and expenses incident to the performance

of the RRA, except for any broker or similar commissions.

In connection with the Series C Offering, the Company and 3i, L.P.

a limited waiver agreement pursuant to which 3i, L.P.

confirmed that the sale and issuance of the Shares will not give rise to any, or

trigger any, rights of termination, defaults, amendment, anti-dilution or similar adjustments, acceleration or cancellation under the

existing agreements with 3i, L.P.

Special Meeting of Stockholders

to a proxy statement filed with the SEC on or about March 6, 2023, (the

“Proxy Statement”), the Company will be holding a Special Meeting of Stockholders (the “Special Meeting”) virtually

online on March 20, 2023.

Stockholders of record of our outstanding shares of Common Stock and Series C Preferred Stock on March 3, 2023

(the “Record Date”) will be entitled to notice of, and to vote at, the Special Meeting and any adjournments, continuations

or postponements thereof that may take place At the Special Meeting, the stockholders of Common Stock and Series C Preferred Stock will

be voting on the following proposals:

(1) to approve an amendment to our Certificate of Incorporation, as amended, to increase the number

of authorized shares from 30,500,000 to 750,500,000, and to increase the number of our common stock from 30,000,000 to 750,000,000, in

substantially the form attached to the Proxy Statement as Appendix A (the “Share Increase Proposal”);

and (2) to approve an

amendment to our Certificate of Incorporation, as amended, in substantially the form attached to the Proxy Statement as Appendix B, to,

at the discretion of the Board of Directors of the Company (the “Board”), effect a reverse stock split with respect to the

Company’s issued and outstanding common stock, par value $0.0001 per share, at a ratio between 1-for-20 and 1-for-35 (the “Range”),

with the ratio within such Range to be determined at the discretion of the Board (the “Reverse Stock Split Proposal”) and

included in a public announcement.

Under the terms of the Series C Preferred Stock, the holders thereof may only vote on Proposal 1 (Share

Increase Proposal) and Proposal 2 (Reverse Stock Split Proposal) and for no other matters.

Each holder of one share of Series C Preferred

Stock is entitled to six hundred twenty (620) votes representing 31,000,000 votes in the aggregate assuming 50,000 shares of Series C

Preferred Stock is outstanding.

Our Therapeutic Candidates

Our most advanced therapeutic

candidate, dovitinib (formerly TKI258), was designed to be a second-generation “pan”-tyrosine kinase inhibitor (TKI) with

the ability to inhibit numerous classes of tumor-driving tyrosine kinases (both receptor and internal), including FGFR, VEGFR, PDGFR,

c-Kit, Flt-3, and CSF-1.

Numerous pan-TKIs are approved and in use for the treatment of cancers, including Sorafenib (NEXAR ® ,

Bayer), Lenvatinib (LENVIMA ® , Eisai), and Tivozanib (FOTIVDA ® AVEO Oncology) and this class of drugs is

increasingly showing promise in combination with immuno-oncology drugs, including checkpoint inhibitors.

Dovitinib was previously developed

by Novartis in 56 clinical trials, and through a Phase 3 clinical trial, where it showed therapeutic equivalence (with similar adverse

events profile) to Bayer’s Sorafenib for the third treatment of mRCC, but failed to show that it was statistically significantly

superior to Sorafenib.

Dovitinib also previously showed encouraging Phase 2 clinical trial results for the treatment of gastrointestinal

stromal tumors (GIST), endometrial cancer, breast cancer, and liver cancer.

We have retrospectively validated our DRP ®

companion diagnostic for dovitinib using clinical trial gene expression data (from patient biopsies) from prior Phase 2 and 3 clinical

trials of this therapeutic candidate.

In retrospective analysis of mRCC, patients selected with our Dovitinib-DRP ® have

an observed fifty percent (50%) increase in median overall survival when compared to DRP ® negative patients.

clinically advance dovitinib in combination with our therapeutic candidate stenoparib in future clinical trials for second-line or later

treatment of metastatic ovarian cancer using our dovitinib-specific DRP ® companion diagnostic to select and treat likely

responder patients.

We believe that dovitinib, if approved, could be broadly applicable and gain market share in the pan-TKI market as

a combination therapy product in other indications as well.

As discussed above, as a result of the FDA’s determination that our

NDA filed on December 21, 2021, was not sufficiently complete to permit a substantive review and therefore was not accepted for filing,

we anticipate that we will need to conduct additional prospective clinical trials to support our retrospective analysis of prior clinical

trials and have decided on advancing dovitinib in combination with our therapeutic candidate, stenoparib, or another approved drug, in

future clinical trials.

Our decision to advance dovitinib as a combination therapy and not as a monotherapy is based on our belief that

both the science and the market for oncology therapies has shifted towards combination therapies and away from monotherapies for multiple

indications of cancer.

We further believe that our DRP ® -Dovitinib companion diagnostic is tumor agnostic and our retrospective

analysis of the clinical data generated in the Novartis clinical studies will also support a companion diagnostic for dovitinib in second-line

or later treatment of metastatic ovarian cancer.

Our second priority therapeutic

candidate, stenoparib, is a selective inhibitor of the key DNA damage repair enzyme poly-ADP-ribose polymerase (PARP), which also has,

in clinically relevant doses, a unique inhibitory action against Tankyrases, another important group of DNA damage repair enzymes.

damage repair mechanisms are crucial to mammalian cell survival and replication, and so inhibition of key DNA damage repair enzymes, such

as PARP, has clinically demonstrated to be therapeutically beneficial in the treatment of cancer.

Tankyrases are enzymes involved in the

stabilization and maintenance of telomeres (the ends of chromosomal DNA) during cell replication, and so disruption of Tankyrases is thought

to provide an additional mechanism of impeding cancer cell growth.

There are four PARP inhibitors currently approved and used for the

treatment of cancers, primarily ovarian and breast cancers.

Most of these approved PARP inhibitors use mutation of BRCA genes, which encode

another important DNA damage repair enzyme as a biomarker for whether the patient will respond to a PARP inhibitor.

The theory is that

tumors already defective in BRCA, which are then treated with an inhibitor of PARP, will suffer higher cell/tumor death than tumors with

active BRCA, effectively resulting from a synergistic inhibition of multiple DNA damage repair pathways.

Stenoparib has demonstrated a

superior therapeutic and toxicity profile compared to competitive PARP inhibitors and has the potential to be a beneficial drug, if approved.

In addition to stenoparib’s dual PARP and Tankyrase inhibitory activity, we believe stenoparib may cross the blood brain barrier

(BBB) — potentially leading to treatment opportunities for primary brain cancers and brain metastases from tumors elsewhere in the

body , and shows less myelotoxicity than the other approved PARP inhibitors.

Additionally, we have developed

and retrospectively validated our Stenoparib-DRP ® companion diagnostic using clinical trial biopsies from the prior Phase

1 clinical trial of this therapeutic candidate.

In retrospective analysis of this trial, we have observed that patients selected with

our Stenoparib-DRP ® have a fourfold (4X) improvement in overall survival when compared to DRP ® negative

Our putative Stenoparib-DRP ® companion diagnostic identified a substantially broader responder patient subgroup

than use of single biomarkers, including BRCA mutation, alone, thus potentially enabling the treatment of more patients.

We plan to apply

for initial market approval for stenoparib, in the U.S., for the treatment of advanced ovarian cancer, using our Stenoparib- DRP ®

companion diagnostic to select and treat likely responder patients or as a combination therapy with our therapeutic candidate, dovitinib.

We are currently advancing a Phase 2 clinical trial for stenoparib for the treatment of advanced ovarian cancer at trial sites in the

and Europe, together with its Stenoparib-specific DRP ® companion diagnostic, for which the FDA has previously approved

an Investigational Device Exemption (IDE) application.

Subject to funding we anticipate commencing a stenoparib in combination with dovitinib

Phase 1b/2 Clinical Trial for second-line or later treatment of metastatic ovarian cancer and/or other solid tumors.

Our third priority therapeutic

candidate, IXEMPRA ® (ixabepilone), is a selective microtubule inhibitor, which interferes with cancer cell division, through

mitotic arrest, leading to cell death.

Microtubules are polymers of the structural protein tubulin that form part of the cytoskeleton

and provide structure and shape to mammalian cells.

They are involved in forming the mitotic spindle apparatus that ensures the proper

segregation of duplicated chromosomes into daughter cells during cell division.

IXEMPRA ® was formerly developed and brought

to market by Bristol-Myers Squibb (BMS) and is currently marketed and sold in the U.S.

by R-PHARM US LLC for the treatment of metastatic

breast cancer treated with two or more prior chemotherapies.

There are numerous microtubule inhibitors currently approved and used for

the treatment of numerous cancers such as ovarian and breast, including Halaven ® (eribulin mesylate), Taxotere ®

(docetaxel), and Abraxane ® (nanoparticle albumin-bound paclitaxel).

Currently marketed microtubule inhibitors have generated

significant sales in the past few years.

For example, sales of Halaven ® (Eisai) alone were about $400 million in 2019.

We have previously developed and retrospectively validated our Ixabepilone-DRP ® companion diagnostic using clinical trial

gene expression data from a prior Phase 2 clinical trial of IXEMPRA ® by BMS.

In retrospective analysis of this trial, patients

selected with our putative Ixabepilone-DRP ® companion diagnostic have an observed 58% increase in complete remission when

compared to randomly selected patients treated with ixabepilone.

We are currently advancing IXEMPRA ® , together with its

DRP ® companion diagnostic, in a Phase 2 European clinical trial in metastatic breast cancer treated with two or more prior

chemotherapies, with the goal of eventually submitting for marketing approval with the EMA for the European market.

R-PHARM US, LLC, holds

a first buy-back option for this asset.

We are also developing, through

external partnerships and out-licensing arrangements, several second priority therapeutic candidates, including a DRP ®

companion diagnostic for LiPlaCis ® and Irofulven in combination with an Irofulven-specific DRP ® companion

diagnostic in order to improve therapeutic benefit and patient outcomes by selecting and treating the patients most likely to respond

to each drug.

LiPlaCis ® is an advanced, targeted liposomal formulation of Cisplatin.

While we previously had an exclusive

in-license to develop this drug from LiPlasome Pharma ApS, on March 28, 2022, we agreed to transfer our exclusive development rights to

Chosa ApS, an affiliate of Smerud Medical Research International AS and have out-licensed our DRP ® companion diagnostic

for LiPlaCis ® to Chosa.

The specific LiPlaCis ® formulation utilizes a proprietary phospholipase A

(sPLA2-IIA) cleavage substrate for controlled, selective hydrolyzation, disruption and release of drug payload in the presence of tumor

This delivery vehicle may result in drug accumulation directly at tumor site, thereby potentially increasing drug targeting at

the tumor and reducing negative, off target drug effects and toxicity that is well known for cisplatin.

We have previously developed and

retrospectively validated a DRP ® companion diagnostic specific for cisplatin, which we believe enables us to identify and

treat the patients most likely to respond to this therapeutic candidate.

Our therapeutic candidate 2X-111

connection with the Series C Offering, concurrently with the SPA, the Company entered into a registration rights agreement with 3i, L.P.

(the “RRA”) pursuant to which the Company is required to file a registration statement with the SEC to register for resale

the shares of Common Stock that are issued upon the potential conversion of the Shares.

Under the terms of the RRA, if we fail file an

Initial Registration Statement (as defined in the RRA) on or prior to its Filing Date (as defined in the RRA), or fail to maintain the

effectiveness of the registration statement beyond defined allowable grace periods set forth in the RRA, we will incur certain registration

delay payments, in cash and as partial liquidated damages and not as a penalty, equal to 2.0% of 3i, L.P.’s subscription amount

of the Shares pursuant to the SPA.

In addition, if we fail to pay any partial liquidated damages in full within 7 days after the date

payment, we will have to pay interest at a rate of 18.0% per annum, accruing daily from the date such partial liquidated damages are

due until such amounts, plus all such interest thereon, are paid in full.

The Company has also agreed to pay all fees and expenses incident

to the performance of the RRA, except for any broker or similar commissions.

In connection with the Series C Offering, the Company and

entered into a limited waiver agreement pursuant to which 3i, L.P.

confirmed that the sale and issuance of the Shares will not

give rise to any, or trigger any, rights of termination, defaults, amendment, anti-dilution or similar adjustments, acceleration or cancellation

under the existing agreements with 3i, L.P.

Meeting of Stockholders

to a proxy statement filed with the SEC on or about March 6, 2023, (the “Proxy Statement”), the Company will be holding a

Special Meeting of Stockholders (the “Special Meeting”) virtually online on March 20, 2023.

Stockholders of record of our

outstanding shares of Common Stock and Series C Preferred Stock on March 3, 2023 (the “Record Date”) will be entitled to

notice of, and to vote at, the Special Meeting and any adjournments, continuations or postponements thereof that may take place At the

Special Meeting, the stockholders of Common Stock and Series C Preferred Stock will be voting on the following proposals:

(1) to approve

an amendment to our Certificate of Incorporation, as amended, to increase the number of authorized shares from 30,500,000 to 750,500,000,

and to increase the number of our common stock from 30,000,000 to 750,000,000, in substantially the form attached to the Proxy Statement

as Appendix A (the “Share Increase Proposal”);

and (2) to approve an amendment to our Certificate of Incorporation, as amended,

in substantially the form attached to the Proxy Statement as Appendix B, to, at the discretion of the Board of Directors of the Company

(the “Board”), effect a reverse stock split with respect to the Company’s issued and outstanding common stock, par

value $0.0001 per share, at a ratio between 1-for-20 and 1-for-35 (the “Range”), with the ratio within such Range to be determined

at the discretion of the Board (the “Reverse Stock Split Proposal”) and included in a public announcement.

Under the terms

of the Series C Preferred Stock, the holders thereof may only vote on Proposal 1 (Share Increase Proposal) and Proposal 2 (Reverse Stock

Split Proposal) and for no other matters.

Each holder of one share of Series C Preferred Stock is entitled to 620 votes representing

31,000,000 votes in the aggregate assuming 50,000 shares of Series C Preferred Stock is outstanding.

Therapeutic Candidate Portfolio

priority therapeutic candidate, stenoparib, is a dual inhibitor of the key DNA damage repair enzyme PARP, as well as Tankyrases, critical

enzymes involved in the WNT signaling pathway commonly activated in many cancers.

DNA damage repair mechanisms are crucial to mammalian

cell survival and replication.

Inhibition of key DNA damage repair enzymes, such as PARP, has clinically demonstrated to be therapeutically

beneficial in the treatment of cancers, including ovarian cancers.

Tankyrases are enzymes involved in the stabilization and maintenance

of telomeres (the ends of chromosomal DNA) during cell replication, Inhibition of tankyrases may provide an additional mechanism of impeding

cancer cell survival and growth.

Tankyrases also play a key role in the WNT signaling pathway- a pathway that is activated in most solid

cancers and that drives cellular proliferation, survival and metastatic capacity.

are four PARP inhibitors currently approved and used for the treatment of cancers, primarily ovarian and breast cancers but now also

pancreatic and prostate cancers.

Most of these approved PARP inhibitors use mutation of BRCA genes, which encode another important DNA

damage repair enzyme, as a biomarker for whether the patient will respond to a PARP inhibitor.

The theory is that tumors already defective

in BRCA, which are then treated with an inhibitor of PARP, will suffer higher cell/tumor death than cells with active, unmutated BRCA,

effectively resulting from a synergistic inhibition of multiple DNA damage repair pathways.

Stenoparib has demonstrated a differentiated

therapeutic and toxicity profile compared to other currently approved PARP inhibitors.

In addition to stenoparib’s dual PARP and

Tankyrase inhibitory activity, preclinical data suggest that stenoparib may cross the blood-brain barrier (BBB) — potentially leading

to treatment opportunities for primary brain cancers as well as brain metastases from other cancers.

Importantly, clinical evidence to

date shows that stenoparib is well tolerated and does not cause the myelotoxicity typical of other approved PARP inhibitors.

Additionally,

we have developed and retrospectively validated our Stenoparib-DRP ® companion diagnostic using clinical trial biopsies

from the prior Phase 1 clinical trial of this therapeutic candidate.

In retrospective analysis of this trial, we have observed that patients

selected with our Stenoparib-DRP ® have a fourfold (4X) improvement in overall survival when compared to DRP ®

negative patients.

Our putative Stenoparib-DRP ® companion diagnostic identified a substantially broader patient

subgroup than those identified by BRCA mutation or homologous repair deficiency, thus potentially enabling the treatment of more patients.

We plan to apply for initial market approval for stenoparib, in the U.S., for the treatment of advanced ovarian cancer, using our Stenoparib-

DRP ® companion diagnostic to select and treat patients likely to derive clinical benefit from stenoparib.

We are currently

advancing a Phase 2 clinical trial for stenoparib for the treatment of advanced, recurrent ovarian cancer at trial sites in the U.S.

and Europe, leveraging the Stenoparib-specific DRP ® companion diagnostic to pre-select patients for enrollment.

of the stenoparib-specific DRP companion diagnostic has been previously approved through the FDA’s Investigational Device Exemption

(IDE) application.

and Out-Licensing Leverage the DRP ® Platform for Other Cancer Therapeutics

have also developed external partnerships and out-licensing arrangements to enable the advance of other therapeutic candidates, LiPlaCis ® ,

2X-111 and Irofulven, leveraging a DRP ® companion diagnostic for each drug.

LiPlaCis ® is an advanced, targeted

liposomal formulation of Cisplatin.

While we previously had an exclusive in-license to develop this drug from LiPlasome Pharma ApS, on

March 28, 2022, we agreed to transfer our exclusive development rights to Chosa ApS, an affiliate of Smerud Medical Research International

AS and have out-licensed our DRP ® companion diagnostic for LiPlaCis ® to Chosa.

The specific LiPlaCis ®

formulation utilizes a proprietary phospholipase A (sPLA2-IIA) cleavage substrate for controlled, selective hydrolyzation,

disruption and release of drug payload in the presence of tumor cells.

This delivery vehicle may result in drug accumulation directly

at tumor site, thereby potentially increasing drug targeting at the tumor and reducing negative, off target drug effects and toxicity

that is well known for cisplatin.

We have previously developed and retrospectively validated a DRP ® companion diagnostic

specific for cisplatin, which we believe enables us to identify and treat the patients most likely to respond to this therapeutic candidate.

is an advanced, targeted liposomal formulation of Doxorubicin, that remains one of the world’s most widely used chemotherapies.

1 unchanged sentence

The specific 2X-111 formulation, which exploits a glutathione

enhanced PEG-liposomal delivery system, we believe may allow 2X-111 to cross the blood-brain barrier (BBB), thereby potentially enabling

the treatment of primary brain tumors, such as glioblastoma multiforme (GBM), and secondary brain tumors that originated from cancers

outside the brain, such as metastatic breast cancer.

The treatment of such brain tumors is a significant unmet need in cancer care, given

that patients with primary brain tumors and metastases have few or no meaningful therapy options.

We have previously developed and retrospectively

validated a DRP ® companion diagnostic specific for epirubicin, which may enable us to identify and treat the patients most

likely to respond to this therapeutic candidate.

2X-111 has previously shown encouraging results in a Phase 2 trial (without use of a

DRP ® companion diagnostic) for the treatment of both GBM and brain metastases of mBC.

In June of 2020, we out-licensed

this program to Smerud Medical Research International, our long-time CRO partner in Europe, which was subsequently terminated on March

28, 2022, in connection with our out-licensing of our DRP ® companion diagnostic for LiPlaCis ® to Chosa discussed

We are currently in discussions with SMERUD about a revised agreement under which SMERUD, together with original drug owner 2BBB

Medicines, B.V., will secure grant funding to advance this program, with DRP ® companion diagnostic support from us.

Irofulven (6-hydroxymethylacylfulvene),

is a unique DNA damaging agent, is a semi-synthetic sesquiterpene derivative of illudin S, a natural toxin isolated from the Jack O’lantern

mushroom ( Omphalotus illudens ).

Until July 23, 2021, we exclusively in-licensed this therapeutic candidate from Lantern Pharma,

enhanced PEG-liposomal delivery system, we believe may allow 2X-111 to cross the BBB, thereby potentially enabling the treatment of primary

brain tumors, such as glioblastoma multiforme (GBM), and secondary brain tumors that originated from cancers outside the brain, such

as metastatic breast cancer.

The treatment of such brain tumors is a significant unmet need in cancer care, given that patients with

primary brain tumors and metastases have few or no meaningful therapy options.

We have previously developed and retrospectively validated

a DRP ® companion diagnostic specific for epirubicin, which may enable us to identify and treat the patients most likely

to respond to this therapeutic candidate.

2X-111 has previously shown encouraging results in a Phase 2 trial (without use of a DRP ®

companion diagnostic) for the treatment of both GBM and brain metastases of mBC.

In June of 2020, we out-licensed this program

to Smerud Medical Research International, our long-time CRO partner in Europe, which was subsequently terminated on March 28, 2022, in

connection with our out-licensing of our DRP ® companion diagnostic for LiPlaCis ® to Chosa discussed above.

(6-hydroxymethylacylfulvene), is a unique DNA damaging agent, is a semi-synthetic sesquiterpene derivative of illudin S, a natural toxin

isolated from the Jack O’lantern mushroom ( Omphalotus illudens ).

Until July 23, 2021, we exclusively in-licensed this therapeutic

candidate from Lantern Pharma, Inc.

Irofulven has two primary anti-tumor mechanisms of action:

first, it produces bulky single strand DNA adducts that are only repairable

by the transcription coupled nucleotide excision repair (TC-NER) pathway;

and second, it stalls RNA polymerase II leading to transcription

and cell cycle arrest and apoptosis.

The therapeutic candidate was formerly developed, between 1995 and 2007, in 41 different clinical

trials, including through Phase 3 clinical trials, which demonstrated Irofulven’s single agent activity in a range of indications,

including castration-resistance prostate cancer (CRPC), ovarian, liver, and pancreatic cancer, and clinical activity in combination treatments

targeting CRPC, colorectal and thyroid cancers.

We have previously developed and patented a putative DRP ® companion diagnostic

specific for Irofulven, which we believe enables us to identify and treat the patients most likely to respond to this therapeutic candidate

although we have not yet filed a PMA with the FDA for this companion diagnostic.

In order to devote more of our development resources

to our priority therapeutic candidates, on July 23, 2021, we terminated our drug development agreement for Irofulven and sold our inventory

of API, our clinical data and records, and our know-how relating to Irofulven to Lantern Pharma, and granted a non-exclusive license to

Lantern Pharma to use our putative DRP ® companion diagnostic specific for Irofulven in exchange for $1 million and future

additional milestone and royalties.

Although we may be entitled to future milestone payments and royalties if Lantern Pharma advances

the development of Irofulven with or without our putative DRP ® companion diagnostic specific for Irofulven, we will no

longer devote any of our development resources to advance this therapeutic candidate.

We retain exclusive worldwide

rights to all the therapeutic candidates in our pipeline, with the exception of IXEMPRA ® for which we have exclusive European

rights and our putative DRP ® companion diagnostic specific for Irofulven, which we have out-licensed to Lantern Pharma,

and our DRP ® companion diagnostic for LiPlaCis ® which we have out-licensed to Chosa.

We have a broad

intellectual property portfolio comprised of more than 17 granted DRP ® patents covering 70 different cancer drugs, and

another 27 DRP ® patent applications pending covering 2 additional cancer drugs.

Our rolling patent strategy allows our

DRP ® patents to be listed in FDA's Orange Book for the drugs where they occur in the approval label.

We also control remaining

composition of matter, formulation, and methods of use patent coverage on dovitinib and stenoparib which extend out to 2028 or 2032 depending

on the relevant patents.

We strive to deliver meaningful

benefit to patients with serious unmet medical needs in oncology by developing potentially breakthrough therapies, together with our proprietary

DRP ® companion diagnostics, in a personalized medicine approach.

The core elements of our strategy include:

Advance our therapeutic candidate, dovitinib,

in combination with our therapeutic candidate, stenoparib, in a Phase 1b/2 clinical trial for second-line or later treatment of metastatic

ovarian cancer and/or other solid tumors, together with our Dovitinib-DRP ® companion diagnostic.

to advance dovitinib as a combination therapy and not as a monotherapy is based on our belief that both the science and the market

for oncology therapies has shifted towards combination therapies and away from monotherapies for multiple indications of cancer.

further believe that our DRP ® -Dovitinib companion diagnostic is tumor agnostic and our retrospective analysis of the

clinical data generated in the Novartis clinical studies will also support a companion diagnostic for dovitinib in second-line or

later treatment of metastatic ovarian cancer.

Accelerate enrollment in, and conclusion of, our ongoing Phase 2 clinical trials for stenoparib in ovarian cancer and IXEMPRA® in metastatic breast cancer.

Our ongoing, DRP®-guided Phase 2 clinical trial of stenoparib as a treatment for ovarian cancer, being conducted at trial sites in the U.S.

and Europe, has been adversely impacted by the COVID-19 pandemic.

We anticipate accelerating enrollment in our stenoparib clinical trial and concluding the clinical trial, with data read out, sometime sometime in the second half of 2023.

Similarly, the recent start of our DRP®-guided Phase 2 clinical trial of IXEMPRA® as a treatment for metastatic breast cancer, being conducted at numerous locations in Europe, has been adversely impacted by the COVID-19 pandemic.

As the regulatory agencies, the internal review boards and the clinical trial sites continue to emerge from COVID-19 pandemic, we anticipate accelerating enrollment in our IXEMPRA ® clinical trial and concluding the clinical trial, with interim data read out, in the second half of 2023.

Support the continuing, external clinical development of our secondary pipeline assets towards value inflection points .

We have previously out-licensed both LiPlaCis ® and 2X-111, to our longtime CRO partner Smerud Medical Research International, in our efforts to advance the clinical development of these assets.

In March 2022, we restructured our LiPlaCis ® license agreements with Smerud and original drug owner LiPlasome Pharma ApS, in a way that will enable Smerud to step into the shoes of Allarity and assume full control of this program for further development in a Smerud affiliate, Chosa ApS, and to secure additional investment funding and collaborative development of the program through the affiliate.

Allarity and SMERUD are currently in discussions about a revised agreement, together with original drug owner 2BBB Medicines, B.V., about future clinical advancement of 2X-111.

We intend to support both of these clinical programs with our proprietary DRP ® companion diagnostics and our clinical trial and regulatory expertise, and are in ongoing negotiations with SMERUD to extend the financing pathways and timeframe for these programs.

Continue to leverage our deep insights in tumor biology and predictive diagnostics to pursue innovative clinical candidates.

We have established, over many years, expertise, and capabilities in the evaluation of oncology therapeutics with coupled companion diagnostics utilizing our proprietary DRP ® platform.

We intend to leverage these capabilities to identify, acquire, and advance additional new, clinical stage assets that may benefit patients with serious unmet medical needs, through a precision medicine approach.

Evaluate strategic opportunities to accelerate development timelines and maximize value of our therapeutic candidate pipeline.

We currently own the exclusive worldwide development and commercial rights to each of our therapeutic candidates, with the exception of IXEMPRA ® , for which we own exclusive European rights, LiPlaCis ® which is now being developed by Chosa ApS, and Irofulven, which is now being developed by Lantern Pharma.

We intend to evaluate collaborations that could maximize the value of our therapeutic candidate pipeline, either through the evaluation of our therapeutic candidates in combination with compounds owned by third parties or through geographic collaborations outside of the U.S.

that allow us to leverage the existing infrastructure of other companies.

For example, there are a number of pharmaceutical companies in oncology markets in the Asia-Pacific, Middle East, and Latin America markets that we believe are interested in partnering with us, and or acquiring license rights from us, in order to develop and commercialize our oncology products in those substantial oncology therapeutics markets.

Our Companion Diagnostics

Overview of Our DRP ® Companion

Diagnostic Platform

Our patented DRP ®

platform is a proprietary technology that enables the development of drug-specific companion diagnostics that are used to identify patients

that will most likely respond to a particular cancer therapy.

While our strategy is to use our DRP ® platform to advance

our own therapeutic candidates, we believe our DRP ® platform could be used by many other cancer drugs, both in clinical

development and those on the market.

A companion diagnostic is

an in vitro diagnostic device or test that provides information that is essential for the safe and effective use of a corresponding

therapeutic product.

After the companion diagnostic is approved for use by the FDA, the use of the companion diagnostic with an approved

therapeutic product is stipulated in the instructions for use in the labeling of both the companion diagnostic and the corresponding therapeutic

In cancer therapy, personalized

medicine, also known as precision medicine, aims to match therapeutic products to those patients (and only those patients) who will positively

respond to that therapeutic product, to maximize the benefits and minimize risks from the therapeutic product received.

Personalized medicine

in the field of oncology therefore depends on (1) understanding the molecular pathophysiology of cancer and (2) the ability of companion

diagnostics to accurately and reliably detect and measure molecular biomarkers.

Consequently, these companion diagnostics inform both

the clinical development of therapeutic candidates and the approved use of therapeutic products.

Our DRP ® platform

facilitates personalized medicine in cancer patients by addressing the crucial fact that the specific cancer tumor biology within a patient

that determines whether a patient will (or will not) respond to a particular cancer drug is largely unique to that patient:

We believe our DRP ®

platform addresses the great complexity of cancer, and is fundamentally different from classical or competitive approaches, in that we

let the tumor tell us what cellular mechanisms are important to its response (or resistance) to a given cancer drug:

Our DRP ® platform

is a powerful bioinformatic engine that is based on advanced systems biology and transcriptomics, meaning that it analyzes all genes that

are transcribed ( i.e .

expressed) as RNA and/or microRNA in a tumor and whether those transcribed genes are affected in response

to treatment of the tumor (or cancer cells) with a given approved drug or therapeutic candidate.

Our approach differs greatly from simple

genetic tests, such as those for a critical mutation in a single gene, and provides a much deeper level of insight into a tumor’s

likelihood of responding to a particular approved drug or therapeutic candidate, that may not be observed by simply looking at a patient’s

DNA sequence information.

When we create a new, drug-specific

DRP ® companion diagnostic using our DRP ® platform, we start with an established panel of cancer cell lines,

which have been treated with the cancer drug or therapeutic candidate, to correlate the genetic expression profile of cell lines that

are either sensitive or resistant to the drug or therapeutic candidate.

In our development of a companion diagnostic, we usually use a

well-known collection of 60 human tumor cell lines from the National Cancer Institute known as the “NCI-60” panel, however

we also use proprietary cancer cell line panels.

Gene expression profiles of the cancer cell lines are derived from a microarray (commercially

available Affymetrix Gene Chips) to quantify the level of mRNA and/or microRNA that have been transcribed from genes in those cells.

advanced bioinformatic algorithm at the heart of our DRP ® platform then identifies, from all mRNA, the specific ones that

are correlated with either drug or therapeutic candidate response or resistance, and the collection of these biomarkers becomes a “fingerprint”

of response (or resistance) to that drug or therapeutic candidate.

Our DRP ® platform then applies what we believe to be

a unique “biological relevance filter” — created from analyzing more than 3,000 actual biopsy samples from human clinical

trials across a broad range of cancer types and cancer drug and therapeutic candidate types — to remove biomarkers that are not

first, it produces bulky single strand

DNA adducts that are only repairable by the transcription coupled nucleotide excision repair (TC-NER) pathway;

and second, it stalls

RNA polymerase II leading to transcription and cell cycle arrest and apoptosis.

The therapeutic candidate was formerly developed, between

1995 and 2007, in 41 different clinical trials, including through Phase 3 clinical trials, which demonstrated Irofulven’s single

agent activity in a range of indications, including castration-resistance prostate cancer (CRPC), ovarian, liver, and pancreatic cancer,

and clinical activity in combination treatments targeting CRPC, colorectal and thyroid cancers.

We have previously developed and patented

a putative DRP ® companion diagnostic specific for Irofulven, which we believe enables us to identify and treat the patients

most likely to respond to this therapeutic candidate although we have not yet filed a PMA with the FDA for this companion diagnostic.

In order to devote more of our development resources to our priority therapeutic candidates, on July 23, 2021, we terminated our drug

development agreement for Irofulven and sold our inventory of API, our clinical data and records, and our know-how relating to Irofulven

to Lantern Pharma, and granted a non-exclusive license to Lantern Pharma to use our putative DRP ® companion diagnostic

specific for Irofulven in exchange for $1 million and future additional milestone and royalties.

Although we may be entitled to future

milestone payments and royalties if Lantern Pharma advances the development of Irofulven with or without our putative DRP ®

companion diagnostic specific for Irofulven, we will no longer devote any of our development resources to advance this therapeutic candidate.

retain exclusive worldwide rights to all the therapeutic candidates in our pipeline, with the exception of IXEMPRA ® for

which we have exclusive European rights and our putative DRP ® companion diagnostic specific for Irofulven, which we have

out-licensed to Lantern Pharma, Inc.

and our DRP ® companion diagnostic for LiPlaCis ® which we have out-licensed

We have a broad intellectual property portfolio comprised of more than 17 granted DRP ® patents covering 70 different

cancer drugs, and another 27 DRP ® patent applications pending covering 2 additional cancer drugs.

Our rolling patent strategy

allows our DRP ® patents to be listed in FDA's Orange Book for the drugs where they occur in the approval label.

control remaining composition of matter, formulation, and methods of use patent coverage on stenoparib which extends out to 2028 or 2032

depending on the relevant patents.

Revised in Q4 2023

strive to deliver meaningful benefit to patients with serious unmet medical needs in oncology by developing potentially breakthrough

therapies, guided by our proprietary DRP ® companion diagnostics, in a personalized medicine approach.

The core elements

of our strategy now include:

all internal resources on accelerating the development of stenoparib in advanced, recurrent

ovarian cancer.

We are currently enrolling patients in both the US and in the UK on a phase

2 study evaluating stenoparib as monotherapy given twice daily (600 mg total dose per day)

in patients with advanced recurrent ovarian cancers regardless of BRCA mutational or homologous

DNA repair status or prior PARP inhibitor treatment.

As reported in a press release December

5, 2023, this trial has already shown promising clinical benefit across all evaluable patients,

including a complete RECIST response.

All patients are pre-selected for enrollment using

the steoparib-specific DRP ® companion diagnostic.

The promise of these emerging

clinical benefit data have prompted the company to deprioritize all other internal clinical

development programs to enable acceleration of the stenoparib monotherapy program in ovarian

Support the continuing,

external clinical development of our secondary pipeline assets towards value inflection points .

We have previously out-licensed

both LiPlaCis ® and 2X-111, to our longtime CRO partner Smerud Medical

Research International, in our efforts to advance the clinical development of these assets.

In March 2022, we restructured

our LiPlaCis ® license agreements with Smerud and original drug owner LiPlasome Pharma ApS, in a way that will enable

Smerud to step into the shoes of Allarity and assume full control of this program for further development in a Smerud affiliate,

Chosa ApS, and to secure additional investment funding and collaborative development of the program through the affiliate.

and SMERUD are currently in discussions about a revised agreement, together with original drug owner 2BBB Medicines, B.V., about

future clinical advancement of 2X-111.

We intend to provide support for both of these clinical programs with our proprietary DRP ®

companion diagnostics and our clinical trial and regulatory expertise, and are in ongoing negotiations with SMERUD to extend

the financing pathways and timeframe for these programs.

of Our DRP ® Companion Diagnostic Platform

patented DRP ® platform is a proprietary technology that enables the development of drug-specific companion diagnostics

that are used to identify patients that will most likely benefit from a particular cancer therapy.

While our strategy is to use our DRP ®

platform to advance our own therapeutic candidates, we believe our DRP ® platform could be used by many other cancer

drugs, both for drugs in clinical development and for those already on the market.

companion diagnostic is an in vitro diagnostic device or test that provides information that is essential for the safe and effective

use of a corresponding therapeutic product.

After the companion diagnostic is approved for use by the FDA, the use of the companion diagnostic

with an approved therapeutic product is stipulated in the instructions for use in the labeling of both the companion diagnostic and the

corresponding therapeutic product.

cancer therapy, personalized medicine, also known as precision medicine, aims to match therapeutic products to those patients (and only

those patients) who will positively benefit from that therapeutic product.

Personalized medicine in the field of oncology therefore depends

on (1) understanding the molecular pathophysiology of cancer and (2) the ability of companion diagnostics to accurately and reliably

detect and measure molecular biomarkers.

Consequently, these companion diagnostics inform both the clinical development of therapeutic

candidates and the approved use of therapeutic products.

DRP ® platform facilitates personalized medicine in cancer patients by addressing the crucial fact that the specific cancer

tumor biology within a patient that determines whether a patient will (or will not) respond to a particular cancer drug is largely unique

to that patient:

believe our DRP ® platform addresses the great complexity of cancer, and is fundamentally different from classical or competitive

approaches, in that we let the tumor tell us what cellular mechanisms are important to its response (or resistance) to a given cancer

DRP ® platform is a powerful bioinformatic engine that is based on advanced systems biology and transcriptomics, meaning

that it analyzes all genes that are transcribed ( i.e .

expressed) as RNA and/or microRNA in a tumor and whether those transcribed

genes are affected in response to treatment of the tumor (or cancer cells) with a given approved drug or therapeutic candidate.

differs greatly from simple genetic tests, such as those for a critical mutation in a single gene and provides a much deeper level of

insight into a tumor’s likelihood of responding to a particular approved drug or therapeutic candidate, that may not be observed

by simply looking at a patient’s DNA sequence information.

we create a new, drug-specific DRP ® companion diagnostic using our DRP ® platform, we start with an established

panel of cancer cell lines, which have been treated with the cancer drug or therapeutic candidate, to correlate the genetic expression

profile of cell lines that are either sensitive or resistant to the drug or therapeutic candidate.

In our development of a companion

diagnostic, we usually use a well-known collection of 60 human tumor cell lines from the National Cancer Institute known as the “NCI-60”

panel, however we also use proprietary cancer cell line panels.

Gene expression profiles of the cancer cell lines are derived from a

microarray (commercially available Affymetrix Gene Chips) to quantify the level of mRNA and/or microRNA that have been transcribed from

genes in those cells.

The advanced bioinformatic algorithm at the heart of our DRP ® platform then identifies, from all

mRNA, the specific ones that are correlated with either drug or therapeutic candidate response or resistance, and the collection of these

biomarkers becomes a “fingerprint” of response (or resistance) to that drug or therapeutic candidate.

platform then applies what we believe to be a unique “biological relevance filter” — created from analyzing more than

3,000 actual biopsy samples from human clinical trials across a broad range of cancer types — to remove biomarkers that are not

relevant to actual clinical response of tumors (from patients) and thus reduce the background noise from our observations.

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expressed genes) comprise a putative DRP ® companion diagnostic for a specific drug or therapeutic candidate.

However, before we can confidently

use the DRP ® companion diagnostic with real cancer patients, either in clinical trials for a therapeutic candidate or for

an approved and on market drug, we must retrospectively validate the predictive power of the DRP ® for that drug or therapeutic

candidate by accessing tumor biopsies (or gene expression data from such biopsies) from prior clinical trials of the drug or therapeutic

candidate, and then retrospectively predicting which patients will respond to the drug or therapeutic candidate.

When possible, we do

our analysis in a “blinded” manner, meaning that we have no access to patient information and whether they did or did not

respond to the drug or therapeutic candidate.

Using this protocol of analysis, we believe we are able to retrospectively validate whether

our putative DRP ® companion diagnostic would have correctly identified those patients who did respond to the drug or therapeutic

At this stage, we also establish a cutoff score for the putative DRP ® companion diagnostic, in order to capture

most of the responsive patients while excluding most of the nonresponsive patients in the tested population.

Typically, we set a DRP ®

cutoff score for a given cancer drug at 50%, although we may use a more stringent cutoff score for certain cancer types or drugs.

The following image shows

an exemplary process flow for creation of our Dovitinib-DRP ® companion diagnostic:

If we succeed with the final

retrospective validation step, then our putative DRP ® companion diagnostic is ready for submission as an IDE to the FDA

and, if approved, use with actual patients in clinical trials.

Depending on the outcomes of our clinical trials, a Pre-Marketing Authorization

(“PMA”) application may be made with the FDA and, if approved, our DRP ® companion diagnostic may be used with

an approved drug in cancer therapy.

The following image shows how to use a drug-specific DRP ® companion diagnostic, in

practice, to test whether a patient will or will not respond to a given cancer drug:

For example, we may receive,

at our diagnostic laboratory (or a partner diagnostic laboratory), a biopsy sample from a hospital or cancer center where a patient is

being treated.

before we can confidently use the DRP ® companion diagnostic with real cancer patients, either in clinical trials for a

therapeutic candidate or for an approved and on-market drug, we must retrospectively validate the predictive power of the DRP ®

for that drug or therapeutic candidate by accessing tumor biopsies (or gene expression data from such biopsies) from prior clinical

trials of the drug or therapeutic candidate, and then retrospectively predicting which patients will respond to the drug or therapeutic

When possible, we do our analysis in a “blinded” manner, meaning that we have no access to patient information

and whether they did or did not respond to the drug or therapeutic candidate.

Using this protocol of analysis, we believe we are able

to retrospectively validate whether our putative DRP ® companion diagnostic would have correctly identified those patients

who did respond to the drug or therapeutic candidate.

At this stage, we also establish a cutoff score for the putative DRP ®

companion diagnostic, in order to capture most of the responsive patients while excluding most of the nonresponsive patients in

the tested population.

Typically, we set a DRP ® cutoff score for a given cancer drug at 50%, although we may use a more

stringent cutoff score for certain cancer types or drugs.

we succeed with the final retrospective validation step, then our putative DRP ® companion diagnostic is ready for submission

as an IDE to the FDA and, if approved, for use with actual patients in clinical trials.

Depending on the outcomes of our clinical trials,

a PMA application may be made with the FDA and, if approved, our DRP ® companion diagnostic may be used with an approved

drug in cancer therapy.

The following image shows how to use a drug-specific DRP ® companion diagnostic, in practice, to

test whether a patient will or will not respond to a given cancer drug:

example, we may receive at our diagnostic laboratory (or a partner diagnostic laboratory), a biopsy sample from a hospital or cancer

center where a patient is being treated.

Often, this biopsy sample is formalin-fixed paraffin-embedded (FFPE).

Generally, we prefer a recent biopsy to an older

diagnostic) biopsy, since tumors may change, at the molecular biology level, with each round of therapy they are treated

Generally, we prefer a

recent biopsy to an older ( e.g .

diagnostic) biopsy, since tumors may change, at the molecular level, with time and after therapy.

Gene expression in tumor cells from the biopsy is determined in the same manner as in the cell lines previously described above.

The expression levels of the relevant biomarkers (that comprise the DRP ® companion diagnostic) in the patient’s tumor

expression levels of the relevant biomarkers (that comprise the DRP ® companion diagnostic) in the patient’s tumor

are compared to the DRP ® reference in order to assess how closely the patient’s biomarker expression levels match

1 unchanged sentence

We then apply the relevant DRP ® score cutoff (e.g.

50%) for that drug to determine whether the patient has

a high enough DRP ® score to be identified as a likely responder for the drug.

Our DRP ® platform

has been retrospectively validated by us using retrospective observational studies in 35 clinical trials that were conducted or sponsored

by other companies.

The FDA considers a retrospective observational study to be one in which the study identifies the population and determines

the exposure/treatment from historical data (i.e.

data generated prior to the initiation of the study) with the variables and outcomes

of interest determined at the time the study is designed.

See, Framework for FDA’s Real-World Evidence Program , page 6 (December

2018), https://www.fda.gov/media/120060/download .

The FDA has accepted our retrospective validation in support of two IDE applications

to conduct clinical trials, one with respect to LiPlaCis ® and one with respect to stenoparib.

We believe our DRP ®

platform has successfully generated drug-specific putative DRP ® companion diagnostics for a broad range of cancer drugs

and therapeutic candidates with different mechanisms-of-action (e.g.

kinase inhibitors, chemotherapeutics, HDAC inhibitors, PARP

inhibitors, hormone receptor inhibitors, etc.) and across both solid and hematological cancers.

Although none of our putative DRP ®

companion diagnostics have yet been approved by the FDA for marketing, the following graphic illustrates some retrospective validations

we have conducted (a strong clinical impact suggests that use of the putative DRP ® companion diagnostic may result in a

3X to 5X increase in therapeutic benefit for DRP ® -selected patients, while a moderate clinical impact suggests that the

DRP ® companion diagnostic may provide a 2X increase in therapeutic benefit):

While these retrospective

observational studies validate the ability of the DRP ® platform to predict likely responders, few of these retrospective

studies meet the criteria for proof of efficacy and safety required by the FDA.

Usually, the FDA requires a sufficiently powered phase

III clinical trial before a PMA may be approved.

Although we believe our DRP ®

platform is very robust and retrospectively validated, we are not always successful in discovering a putative DRP ® companion

diagnostic in all cases.

Generally, the limited number of failures we have encountered have been with cancer drugs with a mechanism-of-action

that is not directly cytotoxic ( i.e.

it acts directly on the cancer cell leading to cell death), such as angiogenesis inhibitors

that interfere with new blood vessel development to the tumor.

Additionally, we have experienced some failures to develop a putative DRP ®

companion diagnostic for a given drug or therapeutic candidate when biopsy materials are too old, or when too many intervening treatments

have taken place from the time of original biopsy to current treatment.

Our DRP ® companion

diagnostics have been patented for more than 70 anticancer agents across a broad range of cancer drugs.

Studies involving our DRP ®

platform, and resulting putative DRP ® companion diagnostics, have also been extensively published in peer reviewed literature

and presented at major oncology conferences.

Advantages Over Other Biomarker Approaches

The realization of personalized

medicine in cancer care has been hampered, in part, due to the general lack of FDA approved companion diagnostics to select and treat

those cancer patients most likely to respond to a given drug (while avoiding treatment of those patients likely to not respond).

lack of suitable companion diagnostics we believe has largely resulted from an outdated and overly simplistic view of cancer, which fails

to adequately address the great complexity of individual tumor responsiveness to a given drug or therapeutic candidate, and which relies

entirely on what the oncology community knows about cancer biology without regard to the much greater body of what we do not know.

historic and competitive companion diagnostic approaches mostly rely on a “knowledge-driven” approach that focus only on single

biomarkers — and not on more informative and reliable, complex biomarker signatures — that rarely hold up in the clinic or

on the market for use with actual patients.

Examples of competitive approaches

and technologies and their shortcomings are:

50%) for that drug to determine whether the patient

has a high enough DRP ® score to be identified as a likely responder for the drug.

DRP ® platform has been validated by us using retrospective observational studies in 35 clinical trials that were

conducted or sponsored by other companies.

The FDA considers a retrospective observational study to be one in which the study identifies

the population and determines the exposure/treatment from historical data (i.e.

data generated prior to the initiation of the study)

with the variables and outcomes of interest determined at the time the study is designed.

See, Framework for FDA’s Real-World

Evidence Program , page 6 (December 2018), https://www.fda.gov/media/120060/download .

The FDA has accepted our retrospective

validation in support of two IDE applications to conduct clinical trials, one with respect to LiPlaCis ® and one with respect

to stenoparib.

We believe our DRP ® platform has successfully generated drug-specific putative DRP ® companion

diagnostics for a broad range of cancer drugs and therapeutic candidates with different mechanisms-of-action (e.g.

kinase inhibitors,

chemotherapeutics, HDAC inhibitors, PARP inhibitors, hormone receptor inhibitors, etc.) and across both solid and hematological cancers.

Although none of our putative DRP ® companion diagnostics have yet been approved by the FDA for marketing, the following

graphic illustrates some retrospective validations we have conducted (a strong clinical impact suggests that use of the putative DRP ®

companion diagnostic may result in a 3X to 5X increase in therapeutic benefit for DRP ® -selected patients, while

a moderate clinical impact suggests that the DRP ® companion diagnostic may provide a 2X increase in therapeutic benefit):

these retrospective observational studies validate the ability of the DRP ® platform to predict likely responders, few

of these retrospective studies meet the criteria for proof of efficacy and safety required by the FDA.

Usually, the FDA requires that

the companion diagnostic be used in a sufficiently powered, prospectively enrolled phase III clinical trial before a PMA may be approved.

we believe our DRP ® platform is very robust and retrospectively validated, we are not always successful in discovering

a putative DRP ® companion diagnostic in all cases.

Generally, the limited number of failures we have encountered have

been with cancer drugs that have a mechanism-of-action that is not directly cytotoxic to cancer cells such as angiogenesis inhibitors

that interfere with new blood vessel development in the tumor microenvironment.

Additionally, we have experienced some failures to develop

a putative DRP ® companion diagnostic for a given drug or therapeutic candidate when biopsy materials are too old, or when

too many intervening treatments have taken place from the time of original biopsy to current treatment.

DRP ® companion diagnostics have been patented for more than 70 anticancer agents across a broad range of cancer drugs.

Studies involving our DRP ® platform, and resulting putative DRP ® companion diagnostics, have also been

extensively published in peer reviewed literature and presented at major oncology conferences.

Over Other Biomarker Approaches

realization of personalized medicine in cancer care has been hampered, in part, due to the general lack of FDA approved companion diagnostics

to select and treat those cancer patients most likely to respond to a given drug (while avoiding treatment of those patients likely to

not respond).

This lack of suitable companion diagnostics we believe has largely resulted from an outdated and overly simplistic view

of cancer, which fails to adequately address the great complexity of individual tumor responsiveness to a given drug or therapeutic candidate.

Accordingly, historic and competitive companion diagnostic approaches mostly rely on a “knowledge-driven” approach that focus

only on single biomarkers — and not on more informative and reliable, complex biomarker signatures.

of competitive approaches and technologies and their shortcomings are:

Gene Mutation Sequencing .

A number of gene mutations have been identified which leads to an alteration in the expressed protein or enzyme, targeted by a drug, which results in the drug no longer binding (or sufficiently binding) to and inhibiting the target.

Such mutations are common in kinases, and thus can lead to failure of targeted kinase inhibitors binding to that target.

Modern “Next Gen Sequencing” (NGS) of such genetic mutations is one current approach to identify patients who may or may not respond to a given cancer drug.

NGS approaches have been commercialized by companies like Foundation Medicine and are also increasingly being used by large cancer centers with their own NGS capabilities.

We believe this approach is largely limited by failing to address complex tumor biology and mechanisms of drug response/resistance, much of which is currently unknown, and, accordingly, can only partially identify patient therapeutic response if it is linked to a single gene mutation.

This approach is also limited to drugs that target proteins or enzymes that have mutations and is thus not suitable for predicting response to drugs such as chemotherapeutics.

Drug Target Expression Analysis .

This approach uses the level of expression of the actual drug target itself as a biomarker for whether a patient will (or will not) respond to a given drug.

A common example is expression of the cell surface receptor tyrosine kinase HER2 used as a companion diagnostic for the HER2-targeting cancer drug Herceptin ® for the treatment of breast cancer.

We believe this approach is also largely limited by failing to address complex tumor biology and mechanisms of drug response/resistance, much of which is currently unknown.

Indeed, many patients who are HER2 positive do not respond well to drugs targeting this receptor and/or patients that initially respond become resistant, indicating other, more complex underlying tumor biology.

“Artificial Intelligence” (AI) or “Machine Learning” (ML) Approaches .

While there are many companies, including in the companion diagnostics space, currently employing technologies that leverage AI or ML, we believe these computer-based technologies are largely limited to the identification and/or design of potential new drug structures.

Currently, we are not aware of any retrospectively or clinically validated, published, or approved companion diagnostic created by any AI-based or ML-based approach.

In contrast to other alternative

companion diagnostics technologies, we believe our DRP ® platform enjoys several, unique competitive advantages:

A number of gene mutations have been identified that alter the expressed protein or enzyme in such a way to preclude drug binding.

Such mutations are common in kinases and can lead to failure of a drug to inhibit its target.

Modern “Next Gen Sequencing”

(NGS) of such genetic mutations is one current approach to identify patients who may or may not respond to a given cancer drug.

approaches have been commercialized by companies like Foundation Medicine and are also increasingly being used by large cancer centers

with their own NGS capabilities.

We believe this approach is largely limited by failing to address complex tumor biology and mechanisms

of drug response/resistance, much of which is currently unknown, and, accordingly, can only partially identify patient therapeutic

response if it is linked to a single gene mutation.

This approach is also limited to drugs that target proteins or enzymes that have

mutations and is thus not suitable for predicting response to drugs such as chemotherapeutics.

Drug Target Expression

This approach uses the level of expression of the actual drug target itself as a biomarker for whether a patient

will (or will not) respond to a given drug.

A common example is expression of the cell surface receptor tyrosine kinase HER2 used

as a companion diagnostic for the HER2-targeting cancer drug Herceptin ® for the treatment of breast cancer.

this approach is also largely limited by failing to address complex tumor biology and mechanisms of drug response/resistance, much

of which is currently unknown.

Indeed, many patients who are HER2 positive do not respond well to drugs targeting this receptor and/or

patients that initially respond become resistant, indicating other, more complex underlying tumor biology.

Intelligence” (AI) or “Machine Learning” (ML) Approaches .

While there are many companies, including in

the companion diagnostics space, currently employing technologies that leverage AI or ML, we believe these computer-based technologies

are largely limited to the identification and/or design of potential new drug structures.

Currently, we are not aware of any retrospectively

or clinically validated, published, or approved companion diagnostic created by any AI-based or ML-based approach.

contrast to other alternative companion diagnostics technologies, we believe our DRP ® platform enjoys several unique competitive

Broadly Applicable .

We believe our DRP ® platform can successfully generate a drug-specific companion diagnostic for most cancer drug types, including:

mechanisms-of-action as diverse as DNA damaging agents,

chemotherapeutics,

targeted kinase inhibitors, and

epigenetic enzyme inhibitors.

We believe our DRP ® platform can successfully generate a drug-specific companion diagnostic for most cancer drug types,

including DNA damaging agents, standard chemotherapeutics, targeted kinase inhibitors and epigenetic enzyme inhibitors.

Retrospectively Validated .

The ability of the DRP ® platform to generate reliable and accurate predictive DRP ® companion diagnostics has been retrospectively validated in more than 35 clinical trials and 1 prospective clinical trial.

The ability of the DRP ® platform to generate reliable and accurate predictive DRP ® companion diagnostics

has been retrospectively validated in more than 35 clinical trials and 1 prospective clinical trial.

Extensively Published .

Studies of our DRP ® platform and putative companion diagnostics have been extensively published in peer-reviewed literature, including publications such as the British Journal of Cancer, Journal of the National Cancer Institute, Plos One, and Breast Cancer Research and Treatment, and have been presented at major oncology conferences, including ASCO, ESMO, and EACR.

Accepted for Use in Clinical Trials by Regulatory Agencies.

Although none of our putative DRP ® companion diagnostics has yet been approved by a regulatory agency for marketing, the U.S.

FDA has previously granted 2 IDE applications approving the use of DRP ® companion diagnostics for both stenoparib and LiPlaCis ® in clinical trials.

The Company previously filed a Pre-Market Approval (PMA) application, with the FDA, for the approval and use of the Dovitinib-DRP ® companion diagnostic as a marketed companion diagnostic for dovitinib in mRCC.

In February 2022 the FDA issued a RTF letter on review of this PMA, largely based on the FDA’s issued RTF letter on the related NDA.

Separately, the stenoparib, IXEMPRA ® and LiPlaCis ® DRP ® companion diagnostics have been accepted for use in clinical trials by national regulatory agencies in the U.S.

Studies of our DRP ® platform and putative companion diagnostics have been extensively published in peer-reviewed literature,

including publications such as the British Journal of Cancer, Journal of the National Cancer Institute, Plos One, and Breast Cancer

Research and Treatment, and have been presented at major oncology conferences, including ASCO, ESMO, and EACR.

Accepted for Use

in Clinical Trials by Regulatory Agencies.

Although none of our putative DRP ® companion diagnostics has yet

been approved by a regulatory agency for marketing, the U.S.

FDA has previously granted 2 IDE applications approving the use of DRP ®

companion diagnostics for both stenoparib and LiPlaCis ® in clinical trials.

The Company previously filed a Pre-Market

Approval (PMA) application, with the FDA, for the approval and use of the Dovitinib-DRP ® companion diagnostic as a

marketed companion diagnostic for dovitinib in mRCC.

In February 2022 the FDA issued a RTF letter on review of this PMA, largely

based on the FDA’s issued RTF letter on the related NDA.

Separately, the stenoparib, IXEMPRA ® and LiPlaCis ®

DRP ® companion diagnostics have been accepted for use in clinical trials by national regulatory agencies in

and/or Europe.

Trusted by Clinicians .

Prominent oncologists at leading cancer centers where we were conducting our DRP ® -guided clinical trials, including Guy’s Hospital (London, England), and Rigshospitalet (Copenhagen, Denmark), have used our putative DRP ® companion diagnostics to select and treat likely responder patients and improve patient outcomes in a personalized medicine approach in such trials.

Our Priority Therapeutic Programs

Overview of Dovitinib (pan-TKI)

Our most advanced therapeutic

candidate, dovitinib (formerly TKI258), is a potent and selective small molecule inhibitor targeting multiple tyrosine kinases.

fibroblast growth factor receptors (FGFR), along with vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth

factor receptor (PDGFR), among others.

During clinical development, with dovitinib’s unique pharmacological profile, the focus was

originally on FGFR driven diseases, and also on those diseases where the additional anti-angiogenesis properties of dovitinib would offer

a therapeutic advantage.

As used in this section of this report describing our therapeutic candidate dovitinib, statements regarding the

use of our proprietary DRP ® companion diagnostics or our proprietary DRP ® platform or our observations that

our therapeutic candidate dovitinib may have anti-cancer or anti-tumor activity or is observed to be well tolerated in a patient population

should not be construed to mean that we have resolved all issues of safety and/or efficacy for our therapeutic candidate dovitinib or

our putative Dovitinib-DRP ® companion diagnostic.

Issues of safety and efficacy for any therapeutic candidate or companion

diagnostic may only be determined by the U.S.

FDA or other applicable regulatory authorities in jurisdictions outside the United States.

Dovitinib exhibits a dual

mechanism of action including anti-tumor effects via its anti-proliferative activity as well as anti-angiogenic activity.

a potent inhibitor of the FGFR1 (inhibitory concentration 50% (IC50) of 8 nM), FGFR2 (IC50 of 40 nM) and FGFR3 (IC50 of 9 nM), as well

as of the VEGFR 1, 2, and 3, PDGFRβ, c-Kit, RET, TrkA, CSF 1R, and FLT3 with IC50s of less than 40 nM.

Stem cell factor (SCF), also

termed KIT ligand or steel factor, has been shown to modulate tumor angiogenesis.

In cultured human endothelial cells and c-Kit expressing

cancer cells, dovitinib was observed to inhibit VEGF and SCF- stimulated mitogenesis;

in a second model of angiogenesis driven by FGF-2,

dovitinib was observed to potently inhibit neovascularization of Matrigel ® plugs in vivo with an average effective dose

(50% inhibition) (ED50) of 3 mg/kg.

The effects on endothelial cells suggest that dovitinib may have potent anti-angiogenic activity.

FGFR and PDGFR are also believed to play a role in the proliferation of certain tumor cells and supporting stromal cells.

of inhibition of target receptor tyrosine kinases (RTKs) by dovitinib, other ligand- stimulated cellular functions are blocked, including

activation of downstream signaling molecules, cellular proliferation, and survival.

Anti-tumor effects for this agent may therefore be

secondary to anti-angiogenesis, anti-proliferative activity against tumor cells, and anti- stromal activity.

Receptor tyrosine kinases

(RTKs) such as VEGFR1,2,3, FGFR1,2,3, and PDGFRβ have been shown to play an important role in tumor angiogenesis (Dvorak 2003).

is produced by both the host and the cancer cells and VEGF has a direct effect on endothelial cells, causing their proliferation, migration,

invasion, and growth (Nagy et al 2002).

Sunitinib and sorafenib, both multi-tyrosine kinase inhibitors that target the VEGF pathways,

have become the standard of care for patients with advanced kidney cancer.

Subsequently, other anti-angiogenic agents including, bevacizumab

in combination with interferon alpha, pazopanib, axitinib and cabozantinib have also been approved by the FDA for advanced RCC.

The mTOR pathway has been

shown to play an important role in angiogenesis through regulation of the synthesis of HIF and proteins that control cell proliferation,

such as c-myc and cyclin D1.

(Jiang BH, Liu LZ.

Role of mTOR in anticancer drug resistance:

perspectives for improved drug treatment.

Drug Resist Update 2008;11(3):63-76.

doi:10.1016/j.drup.2008.03.001).

Based on favorable risk benefit ratio FDA has approved mTOR inhibitors

such as temsirolimus and everolimus for advanced RCC that have demonstrated anti-angiogenesis and anti-tumor activities via action on

HIF and stopping the production of cell-cycle regulators.

All of these targeted therapies have been established as the preferred first

or second line of therapies in patients with advanced RCC, with a median overall survival of up to 26 months, although sorafenib, the

original prototype receptor tyrosine kinase inhibitor (RTKi) has been relegated to the 3 rd line setting following failure of

targeting of the VEGF and mTOR pathways.

Dovitinib was previously developed

by Novartis, through a Phase 3 trial, where it showed therapeutic equivalence (with similar adverse events profile) to Bayer’s Sorafenib

for the treatment of third line RCC, but failed its primary anti-cancer activity endpoint of superiority (to sorafenib) progression-free

survival (PFS).

Dovitinib also previously showed promising Phase 2 results in Novartis sponsored studies for the treatment of gastrointestinal

stromal tumors (GIST), endometrial cancer, breast cancer, and liver cancer.

Pre-Clinical Studies

Dovitinib has demonstrated

activity in a number of in vitro and in vivo models.

It potently inhibits the activity of multiple receptor tyrosine kinases (RTKs) including

PDGFRβ, CSF 1R, KIT, FLT3, VEGFRs 1-3, TrkA, RET, and FGFR (IC50 = 1-40 nM).

Inhibition of these RTKs impedes tumor growth and progression

through different mechanisms, including both direct anti- tumor effects and effects on host tissues, such as endothelial cells and supporting

stromal cells, that are essential for tumor cell proliferation and metastasis.

The in vivo effects of dovitinib

were shown to be a result of its direct anti-tumor effect and also its anti-angiogenic effect.

Direct inhibition of RTK activation on

tumor cells (PDGFRβ, FLT3, and FGFR3) was confirmed by a reduction in phosphorylation of these target RTKs, as well as signaling

pathway components (ERK, STAT5, and AKT) in tumor xenografts.

Target inhibition was observed for as long as 24 h after a single high dose

of dovitinib.

A decrease in tumor cell proliferation and induction of apoptosis, in combination with the anti-angiogenic effect of dovitinib,

resulted in significant anti-tumor activity.

The target RTK profile of dovitinib predicts for activity in many different types of solid

and hematologic tumor models by acting on both endothelial cells and tumor cells.

In the human tumor xenograft models tested, including

colon, prostate, myeloma, AML, breast, and ovarian, dovitinib had anti-tumor effects on both small and large established tumor xenografts.

Studies in the RIP-Tag based

experimental tumor model have shown that tumor angiogenesis can switch from VEGFR dependence to FGFR dependence under anti-VEGF therapy.

This escape mechanism could explain treatment failure with agents targeting single angiogenic targets.

Dovitinib combines potent anti-VEGFR2

and FGFR1-3 activity suggesting the possibility of enhanced response or duration of response in renal tumors compared to agents targeting

Dovitinib was evaluated in

the mouse renal cell carcinoma Renca model.

Renca cells (1 x 106 cells/mouse) were implanted s.c.

into the right flank of Balb/c mice

and treatment was started when the average tumor volume was ~70 mm3.

Dovitinib was also evaluated in two models for human clear cell RCC:

Caki-1, with VHLWT and 786-O with a deletion in the VHL gene and compared to sunitinib and sorafenib.

In both human RCC models, dovitinib

was at least as effective as the two clinically approved inhibitors at their MTDs.

Prior Clinical Trials

Dovitinib has been studied

in 56 prior clinical trials, of which 23 were sponsored by Novartis, and 33 were investigator initiated.

The sponsor initiated trials

are summarized in the following table:

CTKl258 as prefix

Indication/Design/

Study drug dose/

Advanced solid tumors P1 Dose escalation Japan

100 – 500 mg qd 5 days on/2 days off

6 patients treated at

500 mg in SCS

MTD determined to be the 500 mg dovitinib on an oral

once daily, 5 days on, 2 days off schedule

Advanced scirrhous gastric carcinoma

P2, single arm, multicenter

500 mg qd 5 days

on/2 days off

Evaluate the efficacy and safety Early termination.

Acceptable safety profile

Primary endpoint DCR at 8 weeks:

Advanced solid tumors

P1 Dose escalation, multicenter

25 – 100 mg qd

7 days on/7 days off and 100 – 175 qd

7 days on/7 days off

then 28 day cycles

continuous qd dosing

Dose and schedule not similar to pivotal study

MTD defined at 125 mg daily, orally

Acute myloid leukemia P1/2 Dose escalation,

50 – 600 mg qd

7 days on/7 days off

then 28 day cycles

continuous qd

Dose and schedule not similar to pivotal study

2 DLT in 600 mg group

Multiple Myeloma

P1/2 Dose escalation, multicenter

50 – 500 mg qd

x 14 days then

7 day rest followed

by continuous qd

MM pts had neutropenic DLTs not seen in solid tumor

Report combined with A2104

Multiple Myeloma

P1/2 Dose escalation, multicenter

50 mg BID, 100 mg BID, and 325 mg qd continuous dosing

on 28 day cycles

Hematological tumor toxicities differ from solid tumors

A2103 and A2104 were discontinued due to time and dose

dependent accumulation at daily doses above 500 mg

P1/2 Dose escalation, multicenter

200 – 500 mg qd continuous dosing

MTD reached at

Study discontinued due to no clinical

P1, single center, ADME

500 mg radiolabeled dose day 1 followed by 400 mg qd

continuous dosing

Terminal half life about 32 hours.

Elimination via oxidative

Metastatic RCC

P1/2, Dose escalation and expansion,

US, EU, Taiwan

500 – 600 mg qd 5 days on/2 days off

5 pts at 600 mg and 82 pts

Supportive P1/2 in SCS and SCE + renal impairment (TKI258

renal impairment report – Nov 19, 2013)

MTD was 500 mg 5 days on/2 days off

Disease Control

(CR, PR, SD) 73.3% in the dovitinib 500 mg group per central reading

P1, multicenter, crossover

Arm 1 – Cycle 1:

500 mg single dose crossover Cycle

CSF capsule 500 mg 5 on/2 off

Arm 2 – Cycle 1:

300 mg daily,

crossover for test meals Cycle 2+:

FMI capsule 500 mg 5 on/2 off

Bioavailability Food Effect Capsules

Food had no effect on the systemic

exposure of dovitinib (FMI capsules)

P1, multicenter, crossover

Arm 1 – Cycle 1:

500 mg single dose crossover Cycle 2+:

CSF capsule 500 mg 5 on/2 off

Arm 2 – Cycle 1:

300 mg daily, crossover for test meals Cycle 2+:

FMI tablet 500 mg 5 on/2 off

Bioavailability Food Effect Tablets

Food had no effect on the systemic exposure of dovitinib

(FMI tablets)

CTKl258 as prefix

Indication/Design/

Study drug dose/

P1, multicenter, drug-drug interaction

Cycle 1 DDI between dovitinib and the substrates of

CYP1A2, CYP2C19, CYP2C9, and CYP3A4

Dovitinib is a strong inducer of CYP1A2 and a moderate

inhibitor f CYP2C19 and CYP3A4/5

Solid tumors, excluding breast cancer

P1, multicenter, drug-drug interaction

Cycle 1 DDI between dovitinib and the inhibitor of CYP1A2

Fluvoxamine, a CYP1A2 inhibitor showed weak to moderate

inhibition of dovitinib metabolism

Mild, moderate and severe hepatic

impairment cohorts in Patients w/ Solid Tumors

P1, multicenter, hepatic impairment

Single dose PK followed by multiple dose PK 400 mg or

7 Mild 400 mg:

12 Mild 500 mg:

Closure of the study before the tolerated dose was identified

in any of the hepatic impaired group.

Dovitinib label:

Excluding patients with moderate and

severe hepatic impairment from treatment with dovitinib

P1, multicenter, crossover

500 mg 5 on/2 off crossover in PK phase

Bioequivalence Capsules FMI vs.

Bioequivalence established between capsules and tablets

Urothelial Cancer

NA, EU Taiwan

500 mg qd 5 days on/2 days off

ORR in FGR3 wildtype:

FGFR3 mutated:

Metastatic Breast Cancer

P2, multicenter

NA, EU, Taiwan

500 mg qd 5 days on/2 days off

FGFR1+/HR+ 65.2%

FGFR1-/HR+ 39.1%

Multiple myeloma

P2, multicenter

NA, EU, Australia, Turkey

500 mg qd 5 days on/2 days off

Hematological tumor toxicities differ from solid tumors

Terminated after stage 1 according

Hepatocellular carcinoma 1 st

P2, multicenter

500 mg qd X 5 days

on/2 days off with Pop PK Vs Sorafenib 400 mg bid

165 (dovitinib 82, sorafenib

Phase 2 randomized in SCS

Metastatic breast cancer, HER2-,

P2, randomized, double blind, placebo

Fulvestrant + dovitinib 500 mg qd 5 days on/2 days off

Fulvestrant + Placebo

47 (fulvestrant+

(fulvestrant+

PFS HR 0.681 (95% CI:

0.406, 1,143)

Endometrial cancer with or without

FGFR2 mutation

P2, multicenter, single arm

500 mg qd 5 days on/2 days off

PFS at 28 weeks

31.8% in FGFR2 mutated

29.0% in FGFR2 wild type

Advanced RCC after failure of at least 1 VEGF and 1

mTOR targeted therapy

500 mg qd X 5 days

on/2 days off with Pop PK Vs Sorafenib 400 mg bid

570 (dovitinib 284, sorafenib

Phase 3, pivotal in SCS & SCE

Progressed on imatinib

500 mg qd X 5 days

Phase 2 Investigator initiated

DCR at 12 weeks

Progressed on imatinib and sunitinib

500 mg qd X 5 days

Phase 2 Investigator initiated No CSR only a publication

al., British Journal of Cancer (2013) 109, 2309 – 2315

DCR at 24 weeks

We believe the clinical data

in these trials justify further clinical trials for dovitinib in GIST, endometrial cancer, ovarian cancer, breast cancer, RCC, and hepatocellular

carcinoma (HCC or liver cancer).

The studies in clear cell

renal carcinoma, A2302 and A2107, were the pivotal and the supporting study, respectively, in the dovitinib NDA, as well as PD02-044,

the Dovitinib-DRP ® validation study.

The indication for the NDA was treatment of patients with advanced RCC following two

or more prior systemic therapies and who are selected for therapy with the Dovitinib-DRP ® companion diagnostic.

above, based upon the reasons given in the RTF letters and a subsequent Type C meeting with the FDA on May 31, 2022, we anticipate that

the FDA will require a prospective Phase 3 clinical trial as well as additional dose optimization studies before regulatory approval of

Dovitinib as a monotherapy and its companion diagnostic Dovitinib-DRP for the treatment of third-line mRCC can be obtained.

A2107 is a Phase I/II study

on a 5-day on/2-day off treatment schedule in heavily pre-treated advanced RCC patients that are refractory to standard therapies.

the 20 patients treated in phase I with 500 mg (N = 15) or 600 mg (N = 5) dovitinib, the MTD was defined as 500 mg.

Dovitinib was observed

to be well tolerated and anti-tumor activity was observed after progression on both VEGF and mTOR inhibitors.

In the Phase II portion

of the study, 67 heavily pre-treated patients were enrolled and received 500 mg dovitinib on a 5 days on/2 days off schedule, and had

measurable, histologically or cytologically confirmed progressive advanced or metastatic RCC with predominant clear cell histology.

patients were previously treated with at least 2 prior VEGF inhibitors (most often sunitinib and sorafenib) and one mTOR inhibitor (most

often everolimus), and 55 patients received at least one VEGF and one mTOR inhibitor.

ORR of 3% (90% CI 0.5-9.1), Disease Control Rate

CR, PR, and SD) of 55.2% and a median progression free survival of 3.7 (95% CI 3.0- 5.6) months according to both independent central

review and local review.

A further Phase III registration

trial CTKI258A2302 (study A2302), also referred to as the GOLD trial, was conducted in RCC.

The pivotal Phase III trial was an open-label,

randomized, multi-center study to compare the toleration and anti-cancer activity of dovitinib versus sorafenib in patients (N = 570)

with metastatic RCC after failure of anti-angiogenic (VEGF- targeted and mTOR inhibitor) therapies.

Supportive data from a Phase I/II

dose escalation maximum tolerated dose (MTD) and dose expansion study CTKI258A2107 (study 2107) in patients with advanced or metastatic

RCC (N = 82 at 500 mg) was included in our NDA.

Initially, dovitinib was investigated

with a continuous daily dosing schedule.

However, preliminary PK data suggested that over-proportional drug accumulation might occur with

daily administration.

Therefore, a 5 days on/2 days off dosing schedule was proposed for study A2107.

At the tested dose levels of 500

mg and 600 mg, no over-proportional drug- accumulation was observed on Day 15 (steady state) with the 5 days on/2 days off regimen.

patients presented with dose-limiting toxicities at 600 mg, and the MTD was established at 500 mg.

Accordingly, Novartis selected the

500 mg 5 days on/2 days off regimen for the Phase III registration trial in the advanced RCC indication (study A2302).

Based on the observed anti-tumor

effect of dovitinib against advanced RCC in trial A2107 Novartis proceeded to a Phase III registration trial designed to show superiority

over sorafenib.

A2302 is the Phase III registration trial, also referred to as the GOLD trial.

This pivotal Phase III trial was an open-label,

randomized, multi-center study to compare the tolerability and anti-cancer activity of dovitinib versus sorafenib in patients (N = 570)

with metastatic RCC after failure of anti-angiogenic (one VEGF- targeted and one mTOR inhibitor) and other therapies.

The randomization

was a 1:1 ratio to dovitinib 500 mg/day 5 days on/2 days off vs.

sorafenib 400 mg BID.

The trial failed its primary anti-cancer activity

endpoint of superiority (to sorafenib) progression-free survival (PFS) as determined by central radiology assessment (the median PFS was

3.7 months and 3.6 months in the dovitinib and sorafenib arms, respectively and the HR 0.86 (95% CI:

0.72, 1.04)).

The median overall

survival was 11.9 months for the dovitinib arm and 11.2 months for the sorafenib arm, respectively (HR:

study was published in Lancet Oncology in 2014 where it was concluded that “Dovitinib showed activity, but this was no better

than that of sorafenib in patients with renal cell carcinoma who had progressed on previous VEGF-targeted therapies and mTOR inhibitors.”

The A2302 trial had been designed

to show superiority of dovitinib to sorafenib, and the superiority observed in terms of PFS and OS was not statistically significant.

Subsequently, Novartis did not pursue further development.

However, we believe the trial established that dovitinib is non-inferior to

sorafenib with respect to PFS and OS.

Non-inferior is the statistical term describing a drug that is a drug that shows equivalent therapeutic

benefit to its comparator drug.

However, in evaluating our NDA, the FDA determined that our application using a retrospective analysis

to show dovitinib is non-inferior to sorafenib cannot be based on a Phase 3 clinical trial by Novartis designed to show that dovitinib

is superior to sorafenib that failed its designed endpoints.

The two key requirements for

the non-inferiority approach are (i) the presence of assay sensitivity of the pivotal study, a finding that is readily demonstrable for

the A2302 study, and (ii) the choice of non-inferiority margin, based upon a combination of statistical reasoning and clinical judgement

by RCC-subspecialized practitioners offering their clinical perspective on the retention of efficacy needed for the intervention to be

considered “efficacious” in that particular malignancy and specific disease setting.

The non-inferiority margin for the hazard

ratio, i.e., 1.153, was determined using studies that are all phase 3, randomized controlled trials (RCTs) where sorafenib was administered

as second-line, third-line, or fourth-line treatment.

As mentioned above, in the A2302 study, the point estimate of the hazard ratio on

PFS was 0.86, and its two-sided 95% confidence interval was (0.72, 1.04).

Since the upper bound margin of 95% CI in the unstratified analysis

of PFS was 1.04, we believe the non-inferiority of dovitinib to sorafenib is demonstrated because the upper limit (1.04) was less than

the estimated margin of 1.153.

Subgroup and sensitivity analyses of PFS were consistent with the primary analysis demonstrating the efficacy

of dovitinib in this patient population.

Patients with KPS ≥ 90 had a higher median PFS in the dovitinib group (median 18.4 months,

12.9, Not evaluable) than the sorafenib group (median 13.9, 95% CI:10.7, 15.5).

The post hoc non-inferiority

analysis on the OS was performed using a hazard ratio (HR on OS;

dovitinib/sorafenib as secondary endpoint) with a margin of 1.153 with

the same hypothesis used for PFS.

The OS between the dovitinib and sorafenib treatment groups, had a Hazard ratio of 0.94 with 95% CI:

0.779, 1.146%.

Since the upper bound of the two-sided 95% confidence interval for the hazard ratio is <1.153, we believed that the

results showed that dovitinib is non-inferior to sorafenib.

The figures below show the

progression-free and overall survival from the A2302 Phase 3 trial):

The PD02-044 study intended

to identify patients who were more likely to benefit from treatment with dovitinib in the A2302 study and thus validating the Dovitinib-DRP ® .

135 dovitinib-treated patients’ renal biopsy tissue comprised the investigational arm of the “Dovitinib DRP Study”.

Of these 135 patients, 49 patients had a Dovitinib-DRP ® score of> 50%.

The key clinical outcomes of PFS, OS, and ORR

were compared between the 49 patients with a tumor DRP ® score >50% and the sorafenib-treated control arm comprised of

286 patients.

The protocol for the “Dovitinib DRP Clinical Performance Evaluation Study” was submitted with the PMA submission.

The outcome on the efficacy outcome measure, PFS, revealed a 3.75-month median PFS for DRP ® -selected dovitinib-treated

patients versus 3.6-month median PFS for sorafenib-treated patients, yielding an unadjusted HR of 0.714 (95% CI 0.5051, 1.0103;

We believe these results show a marginal and non-significant improvement in median PFS for DRP ® -selected dovitinib-treated

(Please refer to Figure 1 below.)

Kaplan Meier Plot — Summary

of PFS, Efficacy Evaluable Population

The results of the “Dovitinib

DRP Study” on the other efficacy outcome measure OS, revealed a favorable outcome.

It showed a 14.95-month median OS for DRP-selected

dovitinib-treated patients versus an 11.20-month median OS for sorafenib-treated patients.

Comparison of these medians yields an unadjusted

HR of 0.685 (95% CI 0.4736, 0.9897;

p = 0.0439) where the upper bound of the 95% CI does not cross unity, thereby revealing a statistically

significant improvement in median OS for DRP-selected dovitinib-treated patients.

(Please refer to Figure 2 below).

Kaplan Meier Plot — Summary

of OS, Efficacy Evaluable Population

In an exploratory analysis

of the effect of increasing DRP ® score thresholds on clinical outcomes, it was shown that as the DRP ® threshold

increased, so did the clinical outcomes on PFS and OS.

Specifically, when the DRP ® score threshold increased from 50 to

67, the outcome on the primary efficacy endpoint, PFS, further improved to a 5.7-month median PFS for DRP ® -selected dovitinib-treated

patients versus 3.6-month median PFS for sorafenib-treated patients.

Comparison of the median PFS values (resulting from this increase

in the DRP threshold score) yields an unadjusted HR of 0.420 (95% CI 0.2054, 0.8585;

p = 0.0174) and shows a statistically significant

improvement in median PFS for DRP ® -selected dovitinib-treated patients when the DRP ® score threshold is

(Please refer to Figure 3 below).

However, in evaluating our NDA, the FDA determined that our application using a retrospective

analysis to show dovitinib is non-inferior to sorafenib cannot be based on a Phase 3 clinical trial by Novartis designed to show that

dovitinib is superior to sorafenib that failed its designed endpoints.

Kaplan Meier Plot — Summary

of PFS, Cut-Off of 67%, Efficacy Evaluable Population

The following tables summarize

the adverse events observed in the prior Phase 3 trial in RCC:

Most frequently occurring

AEs by MedDRA System Organ Class and Preferred Term:

6.2B TEAEs by MedDRA SOC and PT — Pooled RCC Studies, Safety Population (>5%)

Organ Class (1) Preferred Term (1)

(500 mg/day) N=362

With ≥ 1 TEAE

Number Of TEAEs

And Lymphatic System Disorders

Gastrointestinal

ISS 6.2B TEAEs by MedDRA SOC and PT — Pooled RCC Studies, Safety Population (>5%)

System Organ Class (1)

Preferred Term (1)

Dovitinib (500 mg/day) N=362 n (%)

General Disorders And Administration Site Conditions

General Physical Health Deterioration

Non-Cardiac Chest Pain

Oedema Peripheral

Investigations

Blood Alkaline Phosphatase Increased

Gamma-Glutamyltransferase Increased

Weight Decreased

Metabolism And Nutrition Disorders

Decreased Appetite

Hyperkalaemia

Hypertriglyceridaemia

Musculoskeletal and Connective Tissue Disorders

Muscle Spasms

Musculoskeletal Chest Pain

Musculoskeletal Pain

Pain In Extremity

Nervous System Disorders

Psychiatric Disorders

Respiratory, Thoracic and Mediastinal Disorders

Pleural Effusion

Skin And Subcutaneous Tissue Disorders

Palmar-Plantar Erythrodysaesthesia Syndrome

Vascular Disorders

MedDRA Version 16.0.

All percentages

are based on the number of subjects in the population and treatment group (N).

ISS 6.2B2 TEAEs by MedDRA SOC and PT — Pooled 500 mg Dosing Regimen Studies, Safety

Population (>5%)

System Organ Class (1)

Preferred Term (1)

(500 mg/day) N=664

Subjects With ≥ 1 TEAE

Total Number Of TEAEs

Blood And Lymphatic System Disorders

Thrombocytopenia

Eye Disorders

Lacrimation Increased

Gastrointestinal Disorders

Abdominal Pain

Abdominal Pain Upper

General Disorders And Administration Site Conditions

General Physical Health Deterioration

Non-Cardiac Chest Pain

Oedema Peripheral

Infections And Infestations

Urinary Tract Infection

Investigations

Alanine Aminotransferase Increased

Aspartate Aminotransferase Increased

Blood Alkaline Phosphatase Increased

Blood Bilirubin Increased

Gamma-Glutamyltransferase Increased

Weight Decreased

Metabolism And Nutrition Disorders

Decreased Appetite

Hypertriglyceridaemia

Hypoalbuminaemia

Musculoskeletal And Connective Tissue Disorders

Muscle Spasms

Musculoskeletal Pain

Pain In Extremity

ISS 6.2B2 TEAEs by MedDRA SOC and PT — Pooled 500 mg Dosing Regimen Studies, Safety

Population (>5%)

System Organ Class (1)

Preferred Term (1)

(500 mg/day) N=664

Nervous System Disorders

Psychiatric Disorders

Respiratory, Thoracic And Mediastinal Disorders

Skin And Subcutaneous Tissue Disorders

Dermatitis Acneiform

Palmar-Plantar Erythrodysaesthesia Syndrome

Vascular Disorders

MedDRA Version 16.0.

All percentages

are based on the number of subjects in the population and treatment group (N).

Adverse Events with Incidence ≥ 3.5% (Grade 3/4), Regardless of Study Drug Relationship,

By Preferred Term, Maximum Grade and Treatment (Safety Set)

Preferred Term

Decreased Appetite

Weight Decreased

Hypertriglyceridaemia

Abdominal Pain

Pain In Extremity

Adverse Events with Incidence ≥ 3.5% (Grade 3/4), Regardless of Study Drug Relationship,

By Preferred Term, Maximum Grade and Treatment (Safety Set)

Palmar-Plantar Erythrodysaesthesia Syndrome

Abdominal Pain Upper

Oedema Peripheral

Gamma-Glutamyltransferase Increased

Blood Alkaline Phosphatase Increased

Dermatitis Acneiform

Non-Cardiac Chest Pain

General Physical Health Deterioration

Musculoskeletal Chest Pain

Pleural Effusion

Lipase Increased

Hyperkalaemia

Muscular Weakness

Alanine Aminotransferase Increased

Musculoskeletal Pain

Gastrooesophageal Reflux Disease

Urinary Tract Infection

Aspartate Aminotransferase Increased

Blood Triglycerides Increased

Preferred Terms Are Sorted In Descending Frequency Of All Grades Column, As Reported In Dovitinib Arm.

A Patient with Multiple Occurrences Of An AE Under One Treatment Is Counted Only Once In The AE Category For That Treatment.

A Patient with Multiple Adverse Events Is Counted Only Once In The Total Row.

MedDRA Version 16.0 Has Been Used For The Reporting Of AEs.

AEs Have Been Graded According To The CTCAE V4.03.

Overview of Renal Cell Carcinoma (RCC)

Globally, the incidence of

RCC varies widely from region to region, with the highest rates observed in North America.

Approximately

431,000 new cases of kidney cancer were diagnosed worldwide in 2020 and 179,000 patients died from this malignancy.

In the United States,

there are approximately 79,000 new cases each year and almost 14,000 deaths from RCC on an annual basis.

In Europe, there were approximately

130,000 cases of RCC and 54,000 deaths due to kidney cancer in 2020.

Renal cell carcinomas arise

from the proximal tubal epithelium.

Alternatively known as clear-cell cancer or renal adenocarcinoma, RCC is characterized by a distinct

clear or granular cell appearance visible by light microscopy.

The most common molecular

abnormality in clear cell RCC is loss of Von Hippel-Lindau (VHL), which is found in about 50-70% of sporadic cases.

Sporadic somatic and

hereditary germ cell mutations cause the loss of the VHL protein 9Pvhl0 and VHL negatively regulates hypoxia inducible genes, such as

those encoding Hypoxia-inducible factor (HIF 1)-alpha, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF)

ß and the glucose transporter GLUT-1.

Approximately 25% of the patients

present with advanced disease at the time of diagnosis, including locally invasive or metastatic renal cell carcinoma, and 50% of the

patients undergoing curative surgery can be expected to experience relapse at distant sites.

Median survival for patients with metastatic

disease is approximately 2 years with the 5-year overall survival < 10% that has only improved marginally to 11.7% in the 2007-2013

reporting period.

In the last decade and a half,

the treatment of RCC has evolved from being predominantly cytokine-based to being grounded in the use of drugs targeting VEGF and PDGF,

mammalian target of rapamycin (mTOR) pathways and immunotherapy.

Rationale for Targeting Multiple Kinases in

In the first line setting

of advanced RCC, the established therapeutic options include agents conferring VEGF pathway inhibition, (e.g., sunitinib, pazopanib, and

cabozantinib), mTOR- pathway inhibition (everolimus, temsirolimus), high-dose interleukin (IL)-2, but more recently, this has shifted

to a combination of immune-oncology agents or a combination of immunotherapy with a tyrosine kinase inhibitor.

In the second-line setting,

following progression of disease on therapy, or intolerance of the first- line regimen, there are again a number of potential treatment

options, including targeted drugs such as axitinib, cabozantinib, lenvatinib in combination with everolimus, and the checkpoint inhibitors

nivolumab and iplimumab.

The optimal sequence of therapy remains an area of active research, partially rooted in the observation that

mRCC is a heterogeneous disease characterized by a variable natural history and response to initial and subsequent therapy.

In the third line RCC setting,

there is an unmet need for companion diagnostics, like the Dovitinib-DRP ® , to help guide therapeutic options and decisions

in this patient group.

Until recently, there was no newly approved drug in this setting.

However, tivozanib was recently approved in March

2021 as a treatment option in the third-line RCC setting.

Although these newly approved

targeted agents represent significant progress in the treatment of advanced kidney cancer, the majority of advanced RCC patients become

resistant or refractory to these therapies.

There remains a large and significant unmet medical need for patients whose cancer progresses

despite treatment with VEGF and mTOR inhibitors and immunotherapies.

Thus, the development of novel therapies, particularly in combination

with a predictive biomarker is an unmet medical need in third-line advanced RCC.

Currently, there is just one

novel therapy in patients who have failed two previous systemic therapies, namely, the recently approved TKI tivozanib.

In a retrospective

analysis of 34 patients, third-line sorafenib appears to be active and well tolerated in mRCC after first-line sunitinib and second-line

everolimus or temsirolimus.

In addition, the most recently approved agent, axitinib, in second-line advanced RCC was also based on a Phase

III trial comparing axitinib vs.

Sorafenib was selected as an appropriate active comparator for the dovitinib Phase III trial

(A2302) in patients who failed both anti-VEGF and mTOR therapies.

Existing pan-TKIs and Our Opportunity

Numerous pan-TKIs, including

Nexavar ® (sorafenib), Sutent ® (sunitinib), Votrient ® (pazopanib), and Lenvima ®

(lenvatintib) are currently used in the treatment of RCC and numerous other indications.

Fotivda ® (tivozanib) was recently

approved as a third line RCC treatment, however its use in clinical practice is yet to be established.

The global kinase inhibitor market

in 2019 was roughly $33 billion and, according to consensus estimates cited by Leerink, is poised to grow about 13% annually to surpass

$50 billion by 2022.

Sales of pan-TKIs substantially contribute to this total market.

For example, sales of Sutent ® were

$1 billion in 2018, while sales of Nexavar ® and Votrient ® were each about $800 million that year.

Additionally,

sales of certain pan-TKIs, such as Lenvima ® , are increasingly being driven, in part, by combination therapy with immune

checkpoint inhibitors, such as PD-1 inhibitors (e.g.

Merck’s Keytruda ® ).

In the RCC setting, sales of Nexavar ®

alone, for example, were $125 million in 2019.

The global kidney cancer drugs market size was valued at $4.4 billion in 2016 and is expected

to grow to $6.3 billion in 2022.

The table below lists the

therapeutic benefit of pan-TKIs, as well as other agents, approved for the treatment of RCC:

Efficacy and MOA of currently available treatments for advanced

renal cell carcinoma — FDA approved

Trt Control/Line of treatment

Dec 2005 Bayer

KIT, FLT3, RET, VEGFR1-3, PDGFRβ, c-CRAF, BRAF, mutantBRAF

Placebo 2 nd -line

5.5 M vs 2.8 M HR=0.44

Jan 2006 Pfizer

VEGFR1-2, FLT3, IT, SCF, PDGFR<

IFN-alpha 1 st -line Previously untreated

10.8 M vs 5.1 M HR=0.42

26.4 vs 21.8 HR=0.72 NS

May 2007 Pfizer

m-Tor inhibitor

IFN-alpha 1 st -line Previously untreated with poor prognostic factors

8.6 vs 4.8 NS

5.5 M vs 3.1 M HR=0.53

7.3 M HR=0.73

March 2009 Novartis

m-Tor inhibitor

Placebo 2 nd -line Previously treated with sunitinib or sorafenib

4.9 M vs 1.9 M HR=0.33 P<0.0001

July 2009 Genentech

Bevacizumab/IFNα

VEGF inhibitor/cytokine

IFN-alpha 1 st -line

9.2 M vs 4.2 M HR=0.60

23 M vs 21 M HR=0.86 NS

Oct 2009 Novartis

FGF1-3, Kit, Itk,

Placebo 1st or 2 nd -line

Trt naïve (54%) or

one prior cytokine trt

9.2 M vs 4.2 M

Jan 2012 Pfizer

PDGFRαβ, c-Kit

Sorafenib 2 nd -line

after failure of

one prior systemic

20.1 vs 19.2 HR=0.97 NS

PD-1 blocking AB

Everolimus 2 nd or 3 rd line treatment after 1 or 2 antiangiogenic therapies

6.0 M vs 6.0 M HR=0.84 p<0.033 mostly 2nd line

25.8 M vs 19.7 M HR=0.73 p<0.0018

May 2016 Eisai

Lenvatinib + everolimus

VEGFR1-3, FGFR1-4, PDGFαβ, KIT, RET/m-Tor

Everolimus (monotherapy) or Lenvatinib (monotherapy) or Lenvatinib + Everolimus 2 nd -line treatment after 1antiangiogenic therapy

vs 5.5 M (E) vs 7.4 M (L) HR=0.37

18.5 M L+E) vs 16.5 M (E) and 17.8 M (L) Label Aug 2018:

25.5 M vs 15.4 M HR=0.67

Dec 2016 Exelixis

VEGFR1-3, KIT, TRBB, FLT-3, AXL, RET, MET, TIE-2

Everolimus 2 nd -line treatment in patients with metastatic renal cell carcinoma who progressed after VEGFR-targeted therapy

17 vs 3 p<0.0001

7.4 M vs 3.8 M HR=0.58 p<0.0001

21.4 M vs 16.5 M HR 0.66 p<0.0003

Trt Control/Line of treatment

Dec 2017 Exelixis

VEGFR1-3, KIT, TRBB, FLT-3, AXL, RET, MET, TIE-2

Sunitinib 1 st -line treatment in patients with advanced renal cell carcinoma of intermediate or poor risk

8.6 M vs 5.3 M HR=0.48 P<0.0008

26.6 M vs 21.2 M HR=0.80

Nivolumab + ipilimumab

PD-1 blocking AB/CTLA-4 blocking AB

Sunitinib 1 st -line treatment in patients with Intermediate- and Poor-Risk Advanced Renal Cell Carcinoma

41.6 vs 26.5 p<0.0001

11.6 M vs 8.4 M HR=0.82 NS

NR vs 26.6 M HR=0.63 p<0.0001

Apr 2019 Merck

Pembrolizumab + axitinib

PD-1 blocking AB/TKI

Sunitinib 1 st -line treatment in patients with advanced renal cell carcinoma

59 vs 36 p<0.0001

15.1 M vs 11.1 M HR=0.69 p<0.0001

HR=0.53 p=0.0001

May 2019 EMD Serono Pfizer

Avelumab + axitinib

PD-L1 blocking AB/TKI

Sunitinib 1 st -line treatment in patients with advanced renal-cell carcinoma

13.8 M vs 7.2 M HR=0.67 p<0.0001

20.1 M vs 19.2 M HR=0.97 NS

Jan 2021 BMS Exelixis

Nivolumab + cabozantinib

PD-1 blocking AB/TKI

Sunitinib 1 st line treatment in patients with advanced renal cell carcinoma

56 vs 27 P<0.0001

16.6 M vs 8.3 M HR=0.51 p<0.0001

Not reached yet HR=0.60 p<0.001

Mar 2021 Aveo

VEGFR1-3 c-kit, PDGFR-β and others

Sorafenib ≥3 line Treatment in relapsed or refractory advanced RCC

5.6 M vs 3.9 M HR=0.73 P=0.016

16.4 M vs 19.2 M HR=0.97 NS

The commercial success of

pan-targeted kinase inhibitors has resulted in the development and FDA approval of seven tyrosine kinases for the treatment of RCC over

the last 15 years.

Adverse grade 3 – 4 events from this class of drugs include hypertension, liver toxicity, GI problems (nausea,

vomiting, diarrhea), anemia, lymphocytopenia, thrombocytopenia, and fatigue.

Other common adverse reactions include anorexia, mucositis,

abdominal pain, palmar-plantar erythrodysesthesia and skin rash.

These adverse events vary in frequency and severity among the different

tyrosine kinases approved for RCC.

Additionally, most patients

develop resistance to pan-TKIs via a number of mechanisms (i.e.

genetic alterations, activation of other signaling pathways) or are non-responsive

to a given pan-TKI.

Accordingly, there continues to be a need for the development and approval of additional, new pan-TKIs, both for the

treatment of RCC and other indications.

We believe that our pan-TKI,

dovitinib, together with its DRP ® companion diagnostic — which enables us to select and treat patients most likely

to respond to this drug (while excluding those who will not), uniquely overcomes many of the limitations of current pan-TKIs and, once

it is approved with its DRP ® companion diagnostic by the FDA, has the potential to be a unique drug that can succeed and

compete in the marketplace in numerous cancer indications.

If approved by the FDA, the treating oncologist will have a novel diagnostic

tool, the Dovitinib-DRP ® , to evaluate a cancer patient’s likelihood of responding to treatment with dovitinib and

thus individualize the risk/benefit of this drug, versus other therapeutic options, for the patient.

Future Opportunities & Development Plans

for Dovitinib

We have decided that the costs,

risks and potential benefits of conducting these studies for dovitinib as a monotherapy for mRCC are no longer the best path toward commercial

We continue to evaluate other potential Phase 1b/2 clinical trials for dovitinib combined with other approved drugs in the mRCC

space and in other indications.

For example, subject to funding we anticipate commencing a stenoparib in combination with dovitinib Phase

1b/2 clinical trial for second-line or later treatment of metastatic ovarian cancer and/or other solid tumors.

Our decision to advance

dovitinib as a combination therapy and not as a monotherapy is based on our belief that both the science and the market for oncology therapies

has shifted towards combination therapies and away from monotherapies for multiple indications of cancer.

We further believe that our

DRP®-Dovitinib companion diagnostic is tumor agnostic and our retrospective analysis of the clinical data generated in the Novartis

clinical studies for mRCC will also support a companion diagnostic for dovitinib in second-line or later treatment of metastatic ovarian

cancer, as well as other indications.

In addition, one of dovitinib’s mechanisms of action is to block the formation of new blood

vessels that supply a tumor with nutrients and oxygen (i.e.

inhibition of angiogenesis).

This causes cancer to enter into a state of homologous

recombination deficiency.

Homologous recombination plays an essential role in the repair of DNA double-strand breaks and collapsed replication

Cancer cells that are deficient in homologous recombination become hypersensitive to single strand breaks that, if not repaired,

lead to double strand breaks.

PARP1 is essential for repair of single strand breaks and PARP1 is inhibited by stenoparib.

combined treatment with an antiangiogenic agent and a PARP inhibitor may cause a synthetic lethality, which is a type of genetic interaction

where the combination of two genetic events results in cell death.

Because we hold exclusive, global commercial rights to both dovitinib

and stenoparib, we believe that we can efficiently initiate clinical trials to study the possible synergistic activity achieved by combining

dovitinib and stenoparib.

Additionally, we are developing

a Protocol for a DRP ® -guided Phase 2 trial of dovitinib for the treatment of pediatric osteosarcoma.

This will be preceded

by a Phase 1B dose escalation study in solid tumors in pediatric patients >=2 years of age.

Current FDA regulations require, under

The RACE for Children Act (Title V, Sec.

504, FDA Reauthorization Act (FDARA), enacted August 18, 2017) as part of an NDA submission for

a drug, the concomitant submission of a clinical development plan for the drug in at least one pediatric cancer.

Our planned study for

pediatric osteosarcoma is based on previously conducted, pre-clinical animal model studies of dovitinib showing that the drug has promising

activity in this pediatric indication, which is the most common primary malignant bone tumor in children and young adults.

These pre-clinical

studies were carried out in collaboration with the University of Illinois (Champaign, IL USA).

Clinical development of dovitinib for pediatric

indications will be advanced by OncoHeroes Biosciences, with which we announced a development license and partnership on January 3, 2022.

On September 23, 2022, OncoHeroes announced that it had received a Rare Pediatric Disease Designation (RPDD) from the U.S.

development of Dovitinib for treatment of pediatric osteosarcoma.

This RPDD qualifies OncoHeroes to receive fast track review and a priority

review voucher (PRV) at the time of marketing approval of Dovitinib for a pediatric cancer indication.

We continue to support OncoHeroes

in this pediatric cancer development partnership.

The purpose of the pre-clinical

studies was to investigate the capacity of dovitinib alone, and in combination with a specific checkpoint inhibition strategy (anti-PD-1),

for slowing the progression of experimental pulmonary metastases in animal models of osteosarcoma.

Two separate studies, performed contemporaneously

in a syngeneic, mouse model of experimental pulmonary osteosarcoma metastases in mice using the K7M2 cell line, generated the following

Treatment with dovitinib, compared to control treatment (sucrose solution lacking dovitinib), increased the median survival time by 50%.

Anti-tumor growth activity was also observed for dovitinib as a single agent in this model.

In addition, it was found

that no significant anti-tumor activity was observed in mice treated with single-agent anti-PD-1 antibody at the investigated dosage and

dosing schedule.

Furthermore, the combination of dovitinib and anti-PD-1 antibody did not generate additive or synergistic anti-tumor

activities equal or greater than observed by dovitinib alone in the mouse osteosarcoma model.

DRP ® Companion Diagnostic for

We are developing dovitinib

together with a DRP ® companion diagnostic, which we believe will enable us to select the patients most likely to respond

to the drug in our clinical trials.

A Pre-Market Approval (PMA) application for our Dovitinib-DRP ® companion diagnostic

was filed with the FDA on April 1, 2021.

On February 15, 2022, we received RTF letters for both our dovitinib NDA and our DRP ® -Dovitinib

companion diagnostic PMA.

The FDA has asserted that neither our NDA or PMA meets the regulatory requirements to warrant a complete agency

The primary grounds of rejection asserted by the FDA relates to our use of prior Phase 3 clinical trial data, generated by Novartis

in a “superiority” endpoint study against sorafenib (Bayer), to support a “non-inferiority” endpoint in connection

with the DRP ® -Dovitinib companion diagnostic.

The primary basis for the RTF of our PMA for the DRP ® -Dovitinib

companion diagnostic was the RTF of our NDA for dovitinib, to which our PMA relates.

Allarity anticipates that it may be necessary to

conduct a new, prospective Phase 3 study, to gain approval of dovitinib in the U.S.

The Dovitinib-DRP ®

companion diagnostic, which comprises 58 expressed genes, was initially developed using cell line testing in the NCI60 panel.

The sensitivity

of the 60 cell lines to dovitinib was determined.

The observed difference in sensitivity was correlated to the observed baseline gene

expression in the 60 cell lines and 58 genes were identified as positively correlated or negatively correlated.

The putative Dovitinib-DRP ®

companion diagnostic, developed through our DRP ® platform using gene expression data from cancer cell line testing data,

was positively observed using biopsy materials from five Phase 2 trials of the drug and single Phase 3 trial of the drug, sponsored by

Novartis AG, that were conducted worldwide from 2010-2015 (clinicaltrial.gov numbers NCT01223027, NCT01379534, NCT01232296, NCT01478373,

NCT00958971, NCT01528345).

The following table shows

the primary and secondary endpoints, respectively, in our analysis using a DRP ® score cut-off of 50% is a single Phase

3 trial sponsored by Novartis AG.

All observed measures show an improvement in the DRP ® selected patients from the dovitinib

arm when compared to the sorafenib arm:

Efficacy Parameter

Median PFS, Months

Median OS, Months

188 patients consented in

the dovitinib group, of these, 135 passed established biomarker quality criteria.

The DRP-dovitinib divided the patients into two groups,

sensitive (n=49, DRP score >50%) or resistant (n=86, DRP score < 50%) to dovitinib.

The DRP sensitive population was compared to

the unselected sorafenib group (N=286).

The graphic below shows a Kaplan-Meier curve of overall survival in these two groups.

A statistically significant

improvement in overall survival of patients selected with Dovitinib-DRP ® and treated with Dovitinib, when compared to patients

treated with Sorafenib, is considered a strong argument in favor of regulatory approval of Dovitinib as a monotherapy together with its

companion diagnostic Dovitinib-DRP ® .

However, we anticipate that the FDA will require a prospective Phase 3 clinical trial

as well as additional dosage studies before regulatory approval of Dovitinib as a monotherapy and its companion diagnostic Dovitinib-DRP

We additionally observed that,

as expected, the Dovitinib-DRP ® does not select responders or patients with longer PFS or OS in the sorafenib arm of the

Phase 3 RCC study.

This demonstrates that the DRP ® is highly drug specific, and thus the Dovitinib-DRP ®

cannot be used to select responders to sorafenib.

Certain details of our Dovitinib-DRP ® were published as an e-Poster at

the European Association for Cancer Research (EACR) 2021 Virtual Congress held from June 9 to June 12, 2021, and at the European Society

for Medical Oncology (ESMO) 2021 Virtual Congress held from September 16 to September 21, 2021.

We further tested the predictive

power of the Dovitinib-DRP ® companion diagnostic in other Phase 2 study cohorts from which pre-treatment or diagnostic

biopsies have been obtained, as follows:

HCC (NCT01232296):

Trial A2208 consisted of 82 patients treated frontline with dovitinib and 82 patients treated frontline with sorafenib.

Archival tumor slides or fresh biopsy slides were available for 8 patients from the dovitinib arm and 10 patients from the sorafenib arm.

Endometrial (NCT01379534):

Trial A2211 consisted of 53 patients treated second-line with dovitinib.

Archival tumor slides or tumor blocks were available for 44 patients, of which 35 met the QC criteria during lab analysis.

GIST (NCT01478373):

Trial AIC02 consisted of 38 enrolled patients treated second line dovitinib, biopsies were available and met QC for 16 patients.

Breast cancer combination trial of fulvestrant +/- dovitinib in locally advanced or metastatic breast cancer patients who had evidence of disease progression (NCT01528345, A2210).

47 patients were randomized to fulvestrant+dovitinib, of which 21 had available biopsies that met QC.

Breast cancer monotherapy (NCT00958971, A2202):

1–3 prior therapies in the metastatic setting, N=57 biopsies of which 19 meet QC.

In cohorts from GIST trial

IC02 (second line dovitinib, N=16 biopsies) and breast cancer trial A2202 (1–3 prior therapies in the metastatic setting, N=57 biopsies

of which 19 meet QC) there was no positive association between clinical outcome and DRP ® -Dovitinib prediction.

95% confidence interval of the OS and PFS hazard ratios included those hazard ratios observed for the other cohorts and the RCC phase

In summary, based on these

studies, we believe our putative Dovitinib-DRP ® companion diagnostic accurately and reliably identifies responder patients

(with mRCC, HCC, breast cancer (ER positive) and endometrial cancer) to this therapeutic candidate, and we plan to use this DRP ®

companion diagnostic for all of our clinical programs to advance clinical development of dovitinib for these indications including mRCC.

As discussed above, based upon the reasons given in the RTF letters and a subsequent Type C meeting with the FDA on May 31, 2022, we anticipate

that the FDA will require a prospective Phase 3 clinical trial as well as additional dose optimization studies before regulatory approval

of Dovitinib as a monotherapy and its companion diagnostic Dovitinib-DRP for the treatment of third-line mRCC can be obtained.

have decided that the costs, risks and potential benefits of conducting these studies for dovitinib as a monotherapy for mRCC are no longer

the best path toward commercial success, we continue to evaluate other potential Phase 1b/2 clinical trials for dovitinib combined with

other approved drugs in the mRCC space and in other indications.

For example, subject to funding we anticipate commencing a stenoparib

in combination with dovitinib Phase 1b/2 clinical trial for second-line or later treatment of metastatic ovarian cancer and/or other solid

Our decision to advance dovitinib as a combination therapy and not as a monotherapy is based on our belief that both the science

and the market for oncology therapies has shifted towards combination therapies and away from monotherapies for multiple indications of

We further believe that our DRP ® -Dovitinib companion diagnostic is tumor agnostic and our retrospective analysis

of the clinical data generated in the Novartis clinical studies for mRCC will also support a companion diagnostic for dovitinib in second-line

or later treatment of metastatic ovarian cancer, as well as other indications.

Overview of Stenoparib (PARP inhibitor)

Mechanisms of Action

PARP is an enzyme discovered

more than 40 years ago that produces large, branched chains of poly (ADP) ribose (PAR) from NAD.

In humans, there are 17 members of the

PARP gene family, but most of these are poorly characterized.

Of the 17 PARP family members, only PARP1 and PARP 2 are known to be involved

in DNA repair.

PARP is an abundant nuclear enzyme that is activated by DNA strand breaks to synthesize poly (ADP-ribose) from NAD.

main function of PARP is the maintenance of genomic integrity by facilitating DNA repair through the BER pathway.

BER is one mechanism

by which cancer cells counteract the DNA damage elicited by cytotoxic agents or radiation and thus develop resistance to chemo-or radiation

Prominent oncologists at leading cancer centers where we were conducting our DRP ® -guided clinical trials, including

Guy’s Hospital (London, England), and Rigshospitalet (Copenhagen, Denmark), have used our putative DRP ® companion

diagnostics to select and treat likely responder patients and improve patient outcomes in a personalized medicine approach in such

of Stenoparib, our Novel Dual PARP/ Tankyrase Inhibitor

Mechanism of Action

is an enzyme discovered more than 40 years ago that produces large, branched chains of poly (ADP) ribose (PAR) from NAD.

In humans, there

are 17 members of the PARP gene family, but most of these are poorly characterized.

Of the 17 PARP family members, only PARP1 and PARP

2 are known to be involved in DNA repair.

PARP is an abundant nuclear enzyme that is activated by DNA strand breaks to synthesize poly

(ADP-ribose) from NAD.

The main function of PARP is the maintenance of genomic integrity by facilitating DNA repair through the BER pathway.

BER is one mechanism by which cancer cells counteract the DNA damage elicited by cytotoxic agents or radiation and thus develop resistance

to chemo-or radiation therapies.

PARP inhibition may provide a novel mechanism to sensitize refractory tumors to chemotherapy and radiotherapy.

PARP inhibition has shown

anti-tumor activity in homologous DNA repair-defective tumors, such as those with BRCA1 and BRCA2 mutations.

Also, it is well established

that cells deficient in homologous recombination are particularly sensitive to DNA-crosslinking agents, including the platinum salts (cisplatin

and carboplatin);

their BRCA-selective effects are mediated by a similar mechanism to that of PARP inhibitors.

Therefore, as platinum

salts are frequently used for the treatment of ovarian cancer, including some individuals with BRCA1 or BRCA2 mutations, the combination

with PARP inhibitors and DNA agents is an interesting combination that should be explored in clinical trials.

As used in this section of

this report describing our therapeutic candidate stenoparib, statements regarding the use of our proprietary DRP ® companion

diagnostics or our proprietary DRP ® platform or our observations that our therapeutic candidate Stenoparib may have anti-cancer

or anti-tumor activity or is observed to be well tolerated in a patient population should not be construed to mean that we have resolved

all issues of safety and/or efficacy for our therapeutic candidate Stenoparib or our putative Stenoparib-DRP ® companion

Issues of safety and efficacy for any therapeutic candidate or companion diagnostic may only be determined by the U.S.

or other applicable regulatory authorities in jurisdictions outside the United States.

Stenoparib is a potent inhibitor

of both PARP1 and PARP2 enzymes, as demonstrated in both in vitro and in vivo studies.

Development of stenoparib as single

agent and in combination is supported by preclinical studies.

Stenoparib inhibited proliferation in subsets of cells in cell line panels

derived from a variety of tumors.

Stenoparib, administered as a monotherapy, demonstrated potent tumor growth inhibition in several animal

models with tumors featuring underlying defects in DNA repair, including BRCA mutant breast cancer.

In addition, stenoparib demonstrated

in vivo activity as a single agent in models of B cell lymphoma and AML.

Apart from being a potent

PARP1/2 inhibitor, stenoparib also inhibits PARP5a/5b, otherwise known as tankyrase1 and 2 (TNKS1 and 2), important regulators of canonical

Wnt/Beta-catenin signaling and maintenance of chromosomal telomerase integrity.

Thus, stenoparib inhibited Wnt/Beta-catenin signaling

in colon cancer cell lines, likely through TNKS inhibition.

Consistent with this possibility, stenoparib stabilized axin and TNKS proteins

resulting in Beta-catenin de-stabilization and significantly altered expression of Wnt target genes.

This indicates a potential for treating

several cancers where aberrant activation of Wnt/Beta-catenin signaling can be part of the carcinogenesis and tumor progression.

Temozolomide (TMZ) is a chemotherapeutic

agent with an activity that can be enhanced by PARP inhibition.

PARP inhibition has also been shown to overcome resistance of cells to

inhibition has shown anti-tumor activity in homologous DNA repair-defective tumors, such as those with BRCA1 or BRCA2 mutations.

it is well established that cells deficient in homologous recombination are particularly sensitive to DNA-crosslinking agents, including

the platinum salts (cisplatin and carboplatin) as their BRCA-selective effects are mediated by a similar mechanism to that of PARP inhibitors.

Therefore, as platinum salts are frequently used for the treatment of ovarian cancer, including some individuals with BRCA1 or BRCA2

mutations, the combination with PARP inhibitors and DNA agents is an interesting combination that should be explored in clinical trials.

used in this report, statements regarding the use of our proprietary DRP ® companion diagnostics or our proprietary DRP ®

platform or our observations that our therapeutic candidate Stenoparib may have anti-cancer or anti-tumor activity or is observed

to be well tolerated in a patient population should not be construed to mean that we have resolved all issues of safety and/or efficacy

for our therapeutic candidate Stenoparib or our putative Stenoparib-DRP ® companion diagnostic.

Issues of safety and efficacy

for any therapeutic candidate or companion diagnostic may only be determined by the U.S.

FDA or other applicable regulatory authorities

in jurisdictions outside the United States.

is a potent inhibitor of both PARP1 and PARP2 enzymes, as demonstrated in both in vitro and in vivo studies.

of stenoparib as single agent and in combination is supported by preclinical studies.

Stenoparib inhibited proliferation in subsets of

cells in cell line panels derived from a variety of tumors.

Stenoparib, administered as a monotherapy, demonstrated potent tumor growth

inhibition in several animal models with tumors featuring underlying defects in DNA repair, including BRCA mutant breast cancer.

stenoparib demonstrated in vivo activity as a single agent in models of B cell lymphoma and AML.

addition to being a potent PARP1/2 inhibitor, stenoparib also inhibits PARP5a/5b, otherwise known as tankyrase1 and 2 (TNKS1 and 2),

important in maintaining chromosomal telomerase integrity and in regulating the canonical Wnt/Beta-catenin signaling.

In colon cancer

cell lines, stenoparib inhibited Wnt/Beta-catenin signaling, likely reflecting TNKS inhibition.

Consistent with this possibility, stenoparib

stabilized axin and TNKS proteins resulting in Beta-catenin de-stabilization and significantly altered expression of Wnt target genes.

This indicates a potential for treating several cancers where aberrant activation of Wnt/Beta-catenin signaling can be part of the carcinogenesis

and tumor progression.

(TMZ) is a chemotherapeutic agent with an activity that can be enhanced by PARP inhibition.

PARP inhibition has also been shown to overcome

resistance of cells to TMZ.

Potentiation of TMZ activity was observed in orthotopic models of melanoma and glioblastoma.

In xenograft models, stenoparib inhibition

of PARP was observed in tumor tissue by using the PARP pharmacodynamic assay to measure PAR levels.

The predictive biomarker Ataxia-Telangiectasis

Mutated (ATM) was selected for use in B cell lymphoma by demonstrating that stenoparib sensitivity was increased through ATM loss in these

Certain hematological indications are known to up-regulate P-glycoprotein (P-gp), which is implicated in the development of multidrug

resistance leading to therapeutic failure and poor outcome.

Stenoparib activity is not affected by P-gp over-expression, thus offering

a potential advantage in the clinic.

Pre-Clinical Studies

PARP utilizes nicotinamide

adenine dinucleotide (NAD) as substrate to catalyze the polymerization and transfer of poly (ADP-ribose) (PAR) to acceptor proteins.

posttranslational modification through addition of PAR results in modulation of target protein function.

Stenoparib is a nicotinamide

mimetic, competitive PARP inhibitor that inhibits PARP1 and PARP2 equipotently.

In cell-based assays, stenoparib

potently inhibited proliferation of the BRCA1 mutant human breast cancer cell line MDA-MB-436.

Additionally, stenoparib inhibited proliferation

in the human hematologic cell lines:

SR (B cell lymphoma) and MV-4-11-luc2/AcGFP (acute myeloid leukemia (AML)).

In the murine leukemia

cell line P388, P-glycoprotein (P-gp) overexpression had very little impact on inhibition of proliferation by stenoparib.

Oral administration of stenoparib

for 28 days significantly inhibited tumor growth in vivo in the subcutaneous MDA-MB-436 xenograft model without any significant body weight

A dose- responsive pharmacodynamic effect on PARP activity in MDA-MB-436 xenograft tumor tissue was observed following administration

of a single stenoparib dose.

models, stenoparib inhibition of PARP was observed in tumor tissue by using the PARP pharmacodynamic assay to measure PAR levels.

predictive biomarker Ataxia-Telangiectasis Mutated (ATM) was selected for use in B cell lymphoma by demonstrating that stenoparib sensitivity

was increased through ATM loss in these cells.

Certain hematological indications are known to up-regulate P-glycoprotein (P-gp), which

is implicated in the development of multidrug resistance leading to therapeutic failure and poor outcome.

Stenoparib activity is not

affected by P-gp over-expression, thus offering a potential advantage in the clinic.

utilizes nicotinamide adenine dinucleotide (NAD) as substrate to catalyze the polymerization and transfer of poly (ADP-ribose) (PAR)

to acceptor proteins.

The posttranslational modification through addition of PAR results in modulation of target protein function.

is a nicotinamide mimetic, competitive PARP inhibitor that inhibits PARP1 and PARP2 equipotently.

cell-based assays, stenoparib potently inhibited proliferation of the BRCA1 mutant human breast cancer cell line MDA-MB-436.

Additionally,

stenoparib inhibited proliferation in the human hematologic cell lines:

SR (B cell lymphoma) and MV-4-11-luc2/AcGFP (acute myeloid leukemia

In the murine leukemia cell line P388, P-glycoprotein (P-gp) overexpression had very little impact on inhibition of proliferation

by stenoparib.

administration of stenoparib for 28 days significantly inhibited tumor growth in vivo in the subcutaneous MDA-MB-436 xenograft

model without any significant body weight loss.

A dose- responsive pharmacodynamic effect on PARP activity in MDA-MB-436 xenograft tumor

tissue was observed following administration of a single stenoparib dose.

The decrease in PARP activity was sustained over several hours.

These results demonstrate monotherapy activity

of stenoparib in a BRCA mutant breast cancer model.

Single agent activity was also observed in the AML MV-4-11-luc2/AcGFP survival model.

Treatment with stenoparib resulted in decreased tumor burden as measured by luciferase signal, and reduction in disease translated to

a statistically significant survival benefit.

In addition to activity as

monotherapy, stenoparib demonstrated potentiation of the anti-tumor effects of temozolomide (TMZ), eribulin mesylate (E7389) and carboplatin.

In intracranial survival models of melanoma (murine melanoma B16 cell line) and glioblastoma (human glioblastoma multiforme SJGBM2 cell

line), the addition of stenoparib to TMZ resulted in a significantly increased survival benefit versus that derived from TMZ alone.

Prior Clinical Trials

The initial planned first-in-human

study of stenoparib (conducted by Eisai, Inc.) was an open-Label, Multi center, Phase 1 study of PARP Inhibitor stenoparib (formerly E7449)

as single agent in subjects with advanced solid tumors or with B-cell malignancies and in combination with TMZ or with Carboplatin and

Paclitaxel in Subjects with Advanced Solid Tumors.

The first part (Phase 1) of the study started on January 31, 2012, and was completed

with the last patient visit July 14, 2015.

Further clinical evaluation was stopped, as it was decided to stop the clinical development

for the reasons described below.

Preliminary data after treating the first 28 patients have been presented at ESMO conference 2014.

final data including the retrospective/prospective Stenoparib-DRP ® selection results were presented at ASCO 2018.

The study was conducted as

Phase 1 single-agent arm (Arm 1) and standard 3+3 dose escalation was performed.

During dose escalation, sequential cohorts of 3 to 6

subjects (dose escalation cohorts) were administered increasing doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg (Table 5-1).

41 subjects were enrolled and 33 completed the ‘Treatment phase’ (received first cycle of treatment) while 8 subjects discontinued.

These results demonstrate monotherapy activity of stenoparib in a BRCA mutant breast cancer model.

Single agent activity was also observed

in the AML MV-4-11-luc2/AcGFP survival model.

Treatment with stenoparib resulted in decreased tumor burden as measured by luciferase

signal, and reduction in disease translated to a statistically significant survival benefit.

addition to activity as monotherapy, stenoparib demonstrated potentiation of the anti-tumor effects of TMZ, eribulin mesylate (E7389)

and carboplatin.

In intracranial survival models of melanoma (murine melanoma B16 cell line) and glioblastoma (human glioblastoma multiforme

SJGBM2 cell line), the addition of stenoparib to TMZ resulted in a significantly increased survival benefit versus that derived from

Clinical Trials

initial planned first-in-human study of stenoparib (conducted by Eisai, Inc.) was an open-label, multi center, Phase 1 study of PARP

Inhibitor stenoparib (formerly E7449) as single agent in subjects with advanced solid tumors or with B-cell malignancies and in combination

with TMZ or with Carboplatin and Paclitaxel in Subjects with Advanced Solid Tumors.

The first part (Phase 1) of the study started on

January 31, 2012, and was completed with the last patient visit July 14, 2015.

Further clinical evaluation was stopped, as it was decided

to stop the clinical development for the reasons described below.

Preliminary data after treating the first 28 patients have been presented

at ESMO conference 2014.

The final data including the retrospective/prospective Stenoparib-DRP ® selection results were

presented at ASCO 2018.

study was conducted as Phase 1 single-agent arm (Arm 1) with standard 3+3 dose escalation.

During dose escalation, sequential cohorts

of 3 to 6 subjects (dose escalation cohorts) were administered increasing doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg

41 subjects were enrolled and 33 completed the ‘Treatment phase’ (received first cycle of treatment) while 8

subjects discontinued.

32 subjects continued in the ‘Dose Extension Phase’.

During the Dose Extension Phase, the primary reason for discontinuation

of study treatment was disease progression (27 subjects due to objective disease progression, which was defined as treatment completion).

Two subjects in the 600 mg dose group discontinued study treatment due to AEs with AE being the primary reason for discontinuation as

recorded from the disposition page of the Case Report Form (CRF).

All 41 subjects received at

least 1 dose of stenoparib and were included in the safety, PK, and pharmacodynamics analyses.

12 subjects who received the 600 mg dose

of stenoparib in both fed and fasted states were analyzed for food effect.

After a single or multiple

oral dose, stenoparib was moderately well absorbed with tmax ranging from 0.5 to 4 hours across subjects and dose groups.

The elimination

half-life was approximately 8 hours with less than 1.5% of the administered dose recovered in urine.

Accumulation based on AUC was minimal

(less than 1.2 fold) upon 15 days of dosing across the range of doses.

Stenoparib exposure (both

Cmax and AUC) appeared to be approximately dose proportional following single or multiple oral doses between 50 mg and 800 mg, with slight

deviation at the 400 mg and 600 mg doses.

At the 600 mg dose, food delayed stenoparib absorption as evidenced by a shift in tmax by 2

hours, reduced Cmax by 60%, and increased AUC by 10%.

The interpatient pharmacokinetic variability is large both with and without food.

Thus, the effect of food with the decrease in Cmax, and increase in AUC.

The above figure shows a Linear

Plot of Mean (+SD) E7449 plasma concentration versus nominal time (hours) by treatment fasting and after food intake.

Dose dependent inhibition

of PARP activity, as demonstrated by percent change in PAR levels, was observed.

Maximal inhibition of PARP activity was observed at the

MTD dose (600 mg) of single agent stenoparib.

Evaluation of PAR levels at the MTD dose of stenoparib (600 mg) in the food effect cohort

demonstrated that PAR levels show maximal decrease at 2 to 4 hours post-dose with up to 90% inhibition in PAR levels (from baseline) observed.

Sustained PARP inhibition was observed with a 70% or greater decrease in PAR levels observed at 24 hours post-dose.

Greater decrease in

PAR levels was observed with increasing plasma concentration of stenoparib and with the maximal inhibition observed corresponding to the

peak plasma concentration in measurements obtained at Day-2 and Cycle 1 Day 15.

A greater decrease in PAR levels was observed with

a corresponding higher Cmax when stenoparib was administered without food than when administered with food.

No significant changes in

percent DNA in tail were observed.

In the finalized Phase 1 study,

the majority of subjects (35/41;

85.4%) received up to 8 cycles of treatment with 26 subjects (63.4%) who received up to 2 cycles (<1

cycle = 7, 1 cycle = 5, and 2 cycles = 14);

mean number of treatment cycles overall were 3.8 (median = 2 cycles, range:

During the Dose Extension Phase, the primary

reason for discontinuation of study treatment was disease progression (27 subjects due to objective disease progression, which was defined

as treatment completion).

Two subjects in the 600 mg dose group discontinued study treatment due to AEs, with AE being the primary reason

for discontinuation as recorded from the disposition page of the Case Report Form (CRF).

41 subjects received at least 1 dose of stenoparib and were included in the safety, PK, and pharmacodynamics analyses.

12 subjects who

received the 600 mg dose of stenoparib in both fed and fasted states were analyzed for food effect.

a single or multiple oral dose, stenoparib was moderately well absorbed with tmax ranging from 0.5 to 4 hours across subjects and dose

The elimination half-life was approximately 8 hours with less than 1.5% of the administered dose recovered in urine.

based on AUC was minimal (less than 1.2 fold) upon 15 days of dosing across the range of doses.

exposure (both Cmax and AUC) appeared to be approximately dose proportional following single or multiple oral doses between 50 mg and

800 mg, with slight deviation at the 400 mg and 600 mg doses.

At the 600 mg dose, food delayed stenoparib absorption as evidenced by

a shift in tmax by 2 hours, reduced Cmax by 60%, and increased AUC by 10%.

The interpatient pharmacokinetic variability is large both

with and without food.

Thus, the effect of food decreases Cmax, and increases AUC.

above figure shows a Linear Plot of Mean (+SD) E7449 plasma concentration versus nominal time (hours) by treatment fasting and after

dependent inhibition of PARP activity, as demonstrated by percent change in PAR levels, was observed.

Maximal inhibition of PARP activity

was observed at the MTD dose (600 mg) of single agent stenoparib.

Evaluation of PAR levels at the MTD dose of stenoparib (600 mg) in

the food effect cohort demonstrated that PAR levels show maximal decrease at 2 to 4 hours post-dose with up to 90% inhibition in PAR

levels (from baseline) observed.

Sustained PARP inhibition was observed with a 70% or greater decrease in PAR levels observed at 24 hours

Greater decrease in PAR levels was observed with increasing plasma concentration of stenoparib and with the maximal inhibition

observed corresponding to the peak plasma concentration in measurements obtained at Day-2 and Cycle 1 Day 15.

A greater decrease

in PAR levels was observed with a corresponding higher Cmax when stenoparib was administered without food than when administered with

No significant changes in percent DNA in tail were observed.

the finalized Phase 1 study, the majority of subjects (35/41;

85.4%) received up to 8 cycles of treatment with 26 subjects (63.4%) who

received up to 2 cycles (<1 cycle = 7, 1 cycle = 5, and 2 cycles = 14);

mean number of treatment cycles overall were 3.8 (median =

2 cycles, range:

The overall median duration of treatment for all dose groups was 57 days (range:

1 to 392 days) with an overall median dose intensity

of 11% (range:

1 to 392 days)

with an overall median dose intensity of 11% (range:

1% to 111%) in terms of percentage of planned dose.

In the completed Phase 1 study

the following safety results were reported:

DLTs were reported in 5 of the 25 DLT evaluable subjects, 4 of these occurred at the 800 mg QD dose (1 Grade 3 fatigue and 3 Grade 2 fatigue resulting in administration of less than 75% of the planned dosage of stenoparib) and 1 occurred at the 600 mg QD dose (Grade 3 anaphylactic reaction).

Based on assessment of DLTs, the MTD and RP2D of single agent stenoparib treatment was 600 mg administered orally QD in 28-day cycles.

The mean number of treatment cycles received by the 41 subjects treated at the different dose levels of stenoparib was 3.8 (median = 2 cycles, range:

the completed Phase 1 study the following safety results were reported:

Dose Limiting Toxicities

(DLTs) were reported in 5 of the 25 DLT evaluable subjects, 4 of these occurred at the 800 mg QD dose (1 Grade 3 fatigue and 3 Grade

2 fatigue resulting in administration of less than 75% of the planned dosage of stenoparib) and 1 occurred at the 600 mg QD dose

(Grade 3 anaphylactic reaction).

Based on assessment of DLTs, the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

of single agent stenoparib treatment was 600 mg administered orally once daily (QD) in 28-day cycles.

The mean number of treatment

cycles received by the 41 subjects treated at the different dose levels of stenoparib was 3.8 (median = 2 cycles, range:

The overall median duration of treatment for all dose groups was 57 days (range:

1 to 392 days).

No deaths due to AEs were reported during the study.

Nonfatal SAEs were reported in 58.5% subjects overall.

The majority of SAEs were considered not related to stenoparib treatment and were reported in not more than 1 subject overall;

SAEs reported in more than 2 subjects overall were fatigue (n=3) and lower respiratory tract infection (n=3).

Treatment related SAEs included fatigue (n=3), anemia (n=1), anaphylactic reaction (n=1), drug hypersensitivity (n=1), depression (n=1), pyrexia (n=1), and transaminases increased (n=1).

TEAEs occurred in all study subjects.

The most frequently reported (>30% of subjects overall) TEAEs were fatigue, chromaturia, decreased appetite, nausea, diarrhea, constipation, and vomiting.

No deaths due to AEs were

reported during the study.

Nonfatal Severe Adverse Events (SAEs) were reported in 58.5% subjects overall.

The majority of SAEs were

considered not related to stenoparib treatment and were reported in not more than 1 subject overall;

SAEs reported in more than 2

subjects overall were fatigue (n=3) and lower respiratory tract infection (n=3).

Treatment related SAEs included fatigue (n=3), anemia

(n=1), anaphylactic reaction (n=1), drug hypersensitivity (n=1), depression (n=1), pyrexia (n=1), and transaminases increased (n=1).

Treatment Emergent Adverse

Events (TEAEs) occurred in all study subjects.

The most frequently reported (>30% of subjects overall) TEAEs were fatigue, chromaturia,

decreased appetite, nausea, diarrhea, constipation, and vomiting.

The majority of TEAEs were reported to be Grade 1 or 2 in severity.

1 unchanged sentence

A single Grade 4 AE of non-treatment-related hypokalemia was reported in a subject in the 200 mg dose group.

No Grade 5 (fatal) events were reported.

The most common treatment-related TEAE was fatigue (63%), followed by chromaturia (49%), nausea (34%), diarrhea (29%), and maculo-papular rash (27%).

The majority of treatment-related AEs were Grade 1 or 2 in severity.

With the exception of treatment-related fatigue that was reported to be Grade 3 in severity for 4 subjects (2 subjects each in the 600 mg and 800 mg dose groups), all other Grade 3 treatment-related events were reported in not more than 2 subjects overall (Table 5-4).

The study treatment was discontinued due to AEs in 17% subjects (1/3 subjects in 50 mg, 4/21 subjects in 600 mg, and 2/6 subjects in 800 mg dose groups).

The events leading to treatment discontinuation included fatigue (n=3), diarrhea (n=2), muscular weakness (n=2), nausea (n=1), photosensitivity reaction (n=1), decreased appetite (n=1), paresthesia (n=1), and anaphylactic reaction (n=1).

A total of 24 of 41 subjects (59%) required dose interruptions to manage treatment emergent toxicity.

Dose reductions due to AEs were required in 14.6% subjects overall (1/4 subjects in 400 mg, 2/21 subjects in 600 mg, and 3/6 subjects in 800 mg dose groups).

Skin rash was considered as an event of special interest for stenoparib.

Overall, 41.5% experienced AEs of skin rash with the highest incidence observed in the 800 mg dose group (66.7%) followed by the 600 mg dose group (47.6%).

No Grade 5 (fatal) events

were reported.

The most common treatment-related

TEAE was fatigue (63%), followed by chromaturia (49%), nausea (34%), diarrhea (29%), and maculo-papular rash (27%).

of treatment-related AEs were Grade 1 or 2 in severity.

With the exception of treatment-related fatigue that was reported to be Grade 3

in severity for 4 subjects (2 subjects each in the 600 mg and 800 mg dose groups), all other Grade 3 treatment-related events were

reported in not more than 2 subjects overall (Table 5-4).

The study treatment was

discontinued due to AEs in 17% subjects (1/3 subjects in 50 mg, 4/21 subjects in 600 mg, and 2/6 subjects in 800 mg dose groups).

The events leading to treatment discontinuation included fatigue (n=3), diarrhea (n=2), muscular weakness (n=2), nausea (n=1), photosensitivity

reaction (n=1), decreased appetite (n=1), paresthesia (n=1), and anaphylactic reaction (n=1).

A total of 24 of 41 subjects (59%)

required dose interruptions to manage treatment emergent toxicity.

Dose reductions due to AEs were required in 14.6% subjects overall

(1/4 subjects in 400 mg, 2/21 subjects in 600 mg, and 3/6 subjects in 800 mg dose groups).

Skin rash was considered

as an event of special interest for stenoparib.

Overall, 41.5% experienced AEs of skin rash with the highest incidence observed in

the 800 mg dose group (66.7%) followed by the 600 mg dose group (47.6%).

No serious events of skin rash were reported.

All but 1 event of Grade 3 erythematous rash reported with the 600 mg dose group.

Preliminary anti-cancer activity

assessment was a secondary objective of Phase 1.

Of the total 41 subjects who received single agent stenoparib treatment, best overall

response (BOR) could not be assessed for 6 subjects including 5 subjects who discontinued study treatment prior to the first posttreatment

tumor evaluation and 1 subject who did not have any target lesion (i.e., measurable disease).

None of the 35 subjects assessed had a BOR

of CR based on investigator assessment using RECIST 1.1.

The overall objective response rate (ORR;

CR + PR) was 4.9% (n=2) with 2 PR out

of 41 (both in ovarian cancer), and 31.7% SD (13 out of 41), and disease control rate lasting more than 23 weeks was 24.4% (CR+PR+SD:

Both PRs were predicted by the DRP ® for stenoparib after analyzing biopsies from 13 of the patients.

plot of the individual responses of 35 subjects from the safety cohort is presented below:

Anti-cancer activity according to dose groups

PFS for the whole population

A Kaplan Meier plot of progression free survival of subjects with PR (green line), SD (orange line), NE (yellow line) and

PD (blue line) is below:

The study was published in

the British Journal of Cancer in 2020.

It concluded that the drug stenoparib “showed good tolerability, promising antitumor activity

and significant concentration-dependent PARP inhibition,” and that “The results support further clinical investigation.”

Nevertheless, Eisai decided to pursue other priorities and for undisclosed reasons offered the therapeutic candidate to us because we

had developed a Stenoparib-DRP ® response predictor that we believe could identify the infrequent responding patients.

DRP ® -Guided Phase 2 Trials

We have previously conducted

an open label, single arm Phase 2 study to investigate the toleration and anti-cancer activity of stenoparib in patients with metastatic

breast cancer.

event of Grade 3 erythematous rash reported with the 600 mg dose group.

anti-cancer activity assessment was a secondary objective of the Phase 1 study.

Of the total 41 subjects who received single agent stenoparib

treatment, best overall response (BOR) could not be assessed for 6 subjects including 5 subjects who discontinued study treatment prior

to the first posttreatment tumor evaluation and 1 subject who did not have any target lesion (i.e., measurable disease).

35 subjects assessed had a BOR of Complete Response (CR) based on investigator assessment using RECIST 1.1.

The overall objective response

CR + Partial Response or PR) was 4.9% (n=2) with 2 PR out of 41 (both in ovarian cancer), and 31.7% Stable Disease (SD) (13

out of 41), and disease control rate lasting more than 23 weeks was 24.4% (CR+PR+SD:

Both PRs were predicted by the DRP ®

for stenoparib after analyzing biopsies from 13 of the patients.

A waterfall plot of the individual responses of 35 subjects from

the safety cohort is presented below:

activity according to dose groups

for the whole population was 55 days.

A Kaplan Meier plot of progression free survival of subjects with PR (green line), SD (orange line),

NE (yellow line) and PD (blue line) is below:

study was published in the British Journal of Cancer in 2020.

It concluded that the drug stenoparib “showed good tolerability,

promising antitumor activity and significant concentration-dependent PARP inhibition,” and that “The results support further

clinical investigation.” Nevertheless, Eisai decided to pursue other priorities and for undisclosed reasons offered the therapeutic

candidate to us because we had developed a Stenoparib-DRP ® response predictor that could identify the responsive patients.

DRP ® -Guided

Phase 2 Trials

have previously conducted an open label, single arm Phase 2 study to investigate the tolerability and anti-cancer activity of stenoparib

in patients with metastatic breast cancer.

Patients were selected by having a Stenoparib-DRP ® score of >80%.

Stenoparib was administered as a once

daily oral dose of 600 mg in 21-days cycles (study SMR-3475/2X-1001).

The study was initiated in June 2018 and discontinued in June 2020

due to inconclusive results.

was administered as a once daily oral dose of 600 mg in 21-day cycles (study SMR-3475/2X-1001).

The study was initiated in June 2018

and discontinued in June 2020 due to inconclusive results.

Fourteen patients were enrolled and received at least 1 dose of stenoparib.

The median of number of previous

chemotherapies were 6.

There were 3 patients with ‘stable disease’ response after receiving the treatment, and 1 patient maintained

stable disease for more than 26 weeks until the date of disease progression.

The overall CBR in evaluable population was 9.1%, PFS was

6 weeks, and OC was 8 months.

The most common AE was Fatigue (n = 11;

79%), the second most common AE was decreased appetite and nausea,

respectively (n = 8;

There were 8 SAEs reported by 5 patients, 6 events were unrelated, 1 was unlikely to be related, and 1 event

(urinary tract infection) was possibly related to the treatment.

The data from this mBC trial suggest that a diagnostic biopsy cannot

be used for predicting likelihood of drug response, using the Stenoparib-DRP ® companion diagnostic, in heavily pre-treated

mBC patients, and that new biopsies are needed.

By terminating the mBC study, Allarity has decided to focus on advancing stenoparib in

indications with a higher likelihood of success, including ovarian and pancreatic cancer.

We are further currently

conducting a DRP ® -guided Phase 2, open label, single arm study to investigate the toleration and anti-cancer activity

of the PARP inhibitor, stenoparib in patients with advanced ovarian cancer.

The median of number of previous chemotherapies were 6.

There were 3 patients with ‘stable disease’ after receiving the treatment,

with 1 patient maintaining stable disease for more than 26 weeks.

The overall Clinical Benefit Rate (CBR) in the evaluable population

was 9.1%, Progression Free Survival (PFS) was 6 weeks, and Overall Survival (OS) was 8 months.

The most common Adverse Event (AE) was

Fatigue (n = 11;

79%), the second most common AE was decreased appetite and nausea, respectively (n = 8;

There were 8 Severe AEs

(SAEs) reported by 5 patients, 6 events were unrelated, 1 was unlikely to be related, and 1 event (urinary tract infection) was possibly

related to the treatment.

The data from this mBC trial suggest that a diagnostic biopsy cannot be used for predicting likelihood of drug

response, using the Stenoparib-DRP ® companion diagnostic, in heavily pre-treated mBC patients, and that newer biopsies

By terminating the mBC study, Allarity decided to focus on advancing stenoparib in indications with a higher likelihood of

success, including ovarian and pancreatic cancer.

are currently conducting a DRP ® -guided Phase 2, open label, single arm study to investigate the tolerability and anti-cancer

activity of stenoparib in patients with advanced, recurrent ovarian cancer.

The protocol (2X-1002) addresses unmet medical needs in ovarian

cancer patients that have progressed on previous PARPi therapy without requiring repeat platinum treatment and in selecting both HR proficient

and HR mutated patients/tumors with high likelihood of responding.

The primary endpoint is ORR as determined by RECIST 1.1.

endpoints are CBR, PFS and OS.

This study is being conducted at Guy’s Hospital (London, England), in addition to other trials sites

Patients are selected by using the Stenoparib-DRP ® with a score of >50%.

Stenoparib is administered

as a once daily oral dose of 600 mg in a 28-days cycle (study 2X-1002).

The study was initiated in April 2019 and 10 subjects that were

required to be enrolled independent of DRP ® score have received at least 1 dose of stenoparib and are included in the

safety SAE reporting.

cancer patients that have progressed on previous PARPi therapy without requiring repeat platinum treatment and in selecting both Homologous

Repair (HR) proficient and HR deficient patients/tumors with high likelihood of responding.

The primary endpoint is Overall Response

Rate (ORR) as determined by RECIST 1.1.

Secondary endpoints are CBR, PFS and OS.

This study is being conducted at Guy’s Hospital

(London, England), in addition to other trials sites in the U.S.

Patients are selected by using the Stenoparib-DRP ®

with a score of >50%.

Stenoparib is currently administered twice daily (200 mg in the morning plus 400 mg in the evening for

a total oral dose of 600 mg) in a 28-days cycle (study 2X-1002).

The study was initiated in April 2019 using a single daily dose of 600

10 subjects that were required to be enrolled independent of DRP ® score have received at least 1 dose of stenoparib

and are included in the safety SAE reporting.

Stenoparib-DRP ® -selected patients commenced enrollment in June 2021.

The delay in enrolling

Stenoparib-DRP ® - selected patients has mainly been due to COVID-19 pandemic issues.

Since the Phase 2 studies currently

are ongoing, anti-cancer activity data from these are too early to report.

Overview of Ovarian Cancer

Ovarian Cancer (OC) is a lethal

disease with a 5-year survival rate of 20-30% for advanced OC.

It is the second leading cause of cancer related deaths in women.

proportion of patients with OC are diagnosed at an advanced tumor stage.

The outcome after chemotherapy for advanced OC becomes poorer

and poorer each time a new treatment is introduced following progression on the previous treatment.

Approximately 14,000 OC patients die

each year due to disease progression.

Treatment of OC (as well as

breast cancer (BC)) advanced when the genes BRCA1 and BRCA2 were cloned in the early 1990s and allowing identification of high-risk individuals.

delay in enrolling Stenoparib-DRP ® - selected patients has mainly been due to COVID-19 pandemic issues.

Enrollment on the

twice daily dosing regimen described above began in Q2 2023.

Since the Phase 2 studies currently are ongoing, anti-cancer activity data

from these are too early to report from the full study.

However, as of the 05 December 2023 press release, the current enrollment guided

by DRP ® is showing promising emerging clinical benefit in evaluable patients, including one CR.

of Ovarian Cancer

Cancer (OC) is a lethal disease with a 5-year survival rate of 20-30% for advanced OC.

It is the second leading cause of cancer related

deaths in women.

A large proportion of patients with OC are diagnosed at an advanced tumor stage.

The outcome after chemotherapy for

advanced OC becomes poorer and poorer each time a new treatment is introduced following progression on the previous treatment.

Approximately

14,000 OC patients die each year due to disease progression.

of OC (as well as breast cancer (BC)) advanced when the genes BRCA1 and BRCA2 were cloned in the early 1990s, allowing identification

of high-risk individuals.

These genes encode proteins that are involved in DNA homologous recombination (HR).

Patients harboring germline BRCA1/2 mutations carry

a defective copy of the gene in every cell, which increases the likelihood of cancer developing if the remaining copy becomes defective

through somatic mutation or epigenetic inactivation.

However, there are also patients with germline mutations in other HR pathway genes

and patients who do not carry an inherited germline mutation but have tumors with sporadic HRD mutations.

Data from the Cancer Genome

Atlas (TCGA) demonstrates that approximately fifty percent of high grade serous ovarian cancers have aberrations in HR repair.

Epidemiological studies have

shown an association between germline BRCA1/2 (gBRCA1/2) mutations and the development of OC, (BC), and to a lesser extent pancreatic

and endometrial cancers.

Mutation frequencies are estimated to be approximately 15-20% for those diagnosed with OC and 5% for those diagnosed

with BC (15).

In a recent publication it was shown that for BRCA1 and 2 carriers, cumulative risk for BC by age 80 was 72% and 69%, respectively.

Patients harboring germline

BRCA1/2 mutations carry a defective copy of the gene in every cell, which increases the likelihood of cancer developing if the remaining

copy becomes defective through somatic mutation or epigenetic inactivation.

However, there are also patients with germline mutations

in other HR pathway genes and patients who do not carry an inherited germline mutation but have tumors with sporadic HRD mutations.

from the Cancer Genome Atlas (TCGA) demonstrates that approximately fifty percent of high grade serous ovarian cancers have aberrations

in HR repair.

Epidemiological

studies have shown an association between germline BRCA1/2 (gBRCA1/2) mutations and the development of OC, BC, and to a lesser extent

pancreatic and endometrial cancers.

Mutation frequencies are estimated to be approximately 15-20% for those diagnosed with OC and 5%

for those diagnosed with BC (15).

In a recent publication it was shown that for BRCA1 and 2 carriers, cumulative risk for BC by age 80

was 72% and 69%, respectively.

For OC, cumulative risk was 44% and 17%, respectively.

The peak incidence of BC occurred

in the 41-50-year age group (28.3 per 1000 person-years) for BRCA1 and in the 51-60-year group (30.6 per 1000) for BRCA2 mutation carriers.

The incidence of OC was 3.6 times higher for BRCA1 than BRCA2 carriers, with the peak incidence of cancer occurring regardless of mutation

type among women in the 61-70-year age group (29.4 per 1,000 in BRCA1 carriers).

For BRCA1 and 2 carriers, BC risk increased with the

number of first- and second- degree relatives with breast cancer.

In contrast, OC risk did not vary with respect to family history of

this disease.

DNA repair pathways involving BRCA1/2 engage in single or double stranded DNA breaks, which can occur from damage caused

by ultraviolet light, the generation of reactive oxygen species, ambient or therapeutic irradiation, day- to-day replication errors or

chemical exposure.

Cells lacking a functional BRCA1/2 are also deficient in HR and show a high-degree of chromosomal instability as well

as increased sensitivity to ionizing radiation and chemotherapeutic agents that lead to double-stranded breaks.

Rationale for Targeting PARP in Ovarian Cancer

Poly (ADP-ribose) polymerases

(PARPs) are a family of DNA-dependent nuclear enzymes catalyzing the transfer of ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide

(NAD+) to a variety of target proteins.

There are 17 PARP family member proteins identified through sequence homology of the catalytic

peak incidence of BC occurred in the 41-50-year age group (28.3 per 1000 person-years) for BRCA1 and in the 51-60-year group (30.6 per

1000) for BRCA2 mutation carriers.

The incidence of OC was 3.6 times higher for BRCA1 than BRCA2 carriers, with the peak incidence of

cancer occurring regardless of mutation type among women in the 61-70-year age group (29.4 per 1,000 in BRCA1 carriers).

For BRCA1 and

2 carriers, BC risk increased with the number of first- and second- degree relatives with breast cancer.

In contrast, OC risk did not

vary with respect to family history of this disease.

DNA repair pathways involving BRCA1/2 engage in single or double stranded DNA breaks,

which can occur from damage caused by ultraviolet light, the generation of reactive oxygen species, ambient or therapeutic irradiation,

day- to-day replication errors or chemical exposure.

Cells lacking a functional BRCA1/2 are also deficient in HR and show a high-degree

of chromosomal instability as well as increased sensitivity to ionizing radiation and chemotherapeutic agents that lead to double-stranded

for Targeting PARP in Ovarian Cancer

(ADP-ribose) polymerases (PARPs) are a family of DNA-dependent nuclear enzymes catalyzing the transfer of ADP-ribose moieties from cellular

nicotinamide-adenine-dinucleotide (NAD+) to a variety of target proteins.

There are 17 PARP family member proteins identified through

sequence homology of the catalytic domain.

PARP1, 2 and 3 have all been implicated in DNA repair, with PARP1 being the most abundant.

PARP inhibitors are designed to compete

with NAD+ for the substrate binding to PARP and inhibit PARP activity.

Cells containing dysfunctional BRCA1 or BRCA2 have been shown to

become profoundly sensitized to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and

subsequent apoptosis.

PARP inhibition is thought to induce synthetic lethality, which describes a process where at least two genetic lesions

that individually are not lethal become lethal when combined in the same cell.

For example, cells that are deficient in HR, which is not

lethal in itself, are hypersensitive to a reduction in PARP activity by PARP inhibitors.

However, disruption to other proteins involved

in HR DNA repair other than in BRCA may have the same effect on PARP inhibitor sensitivity.

A further important mechanism

of action for PARP inhibition is the trapping of the PARP1 and PARP2 enzymes at damaged DNA causing cytotoxicity and cell death.

studies have revealed a more complex web of fundamental cellular processes that PARP1 is involved in crucial cell processes other than

in DNA damage repair, such as chromatin remodeling and transcription or regulation of the cell cycle.

There are currently three

PARP inhibitors approved, in a number of countries but not all yet, for either monotherapy or maintenance therapy or both in patients

with advanced OC.

Two are approved in patients with BRCA 1 and 2 mutations with advanced OC having undergone therapy with >3 chemotherapies

(Olaparib) or >2 chemotherapies (Rucaparib).

Two PARPi (niraparib and olaparib) are approved as maintenance therapy in patients with

advanced OC who are in complete or partial response to platinum-based chemotherapy.

The effectiveness of PARP

inhibitors as monotherapy or as maintenance therapy has substantially improved the progression free survival and may be promising for

overall survival in OC patients.

PARP inhibitors as single agents or as potential enhancers of cytotoxic agents that provoke DNA damage,

such as alkylating agents and chemotherapy, have been investigated in a number of studies, including olaparib, rucaparib, niraparib, veliparib,

and talazoparib, where the two latter PARPi are still under development.

There is a current unmet need

for treatment of patients with OC who have progressed on PARPi treatment.

Our ongoing Phase 2 study in ovarian cancer allows for enrollment

of patients previously treated with a PARPi.

We intend to use our Stenoparib-DRP ® to select patients from this group that

will have a high likelihood of responding to our PARPi, Stenoparib.

Future Opportunities & Development Plans

for Stenoparib

Overview of Pancreatic

Ductal Adenocarcinoma (PDAC) & Rationale for Targeting PARP in PDAC

PDAC is the third leading

cause of cancer related death in the United States (2018).

Initial presentation of the disease is typically with metastasis, and the overall

5-year survival for all stages combined is 8%.

Molecular analysis has revealed four subtypes of PDAC giving clinicians further insight

into treating this deadly disease.

One subtype that has been elucidated and termed “unstable” is significant for the presence

of DNA damage repair deficiency and can be targeted by several old and emerging therapies.

One such therapy that may be considered are

PARP inhibitors.

There have been reports of

responses seen to PARP inhibitors in individuals with pancreatic cancer, and there are clinical trials currently (NCT03140670, NCT02184195,

NCT01585805) for this patient population.

One PARPi (olaparib) was approved by the FDA in December 2019 for the treatment of BRCA1/2 mutated

Due to the relatively common DNA repair pathway mutations in PDAC tumors, PARP inhibition may be a potential therapeutic option

in individuals with advanced PDAC with the HRD phenotype.

Development Plan for Stenoparib

This study would be performed

as an open, uncontrolled Phase II study of stenoparib in up to 30 advanced PDAC patients.

Patients with predicted high likelihood of responding

to stenoparib, after inclusion in the pre-screening protocol using the Stenoparib-DRP ® companion diagnostic will be included

in the study.

In this study, a high likelihood of response to stenoparib will be defined as the patient having a Stenoparib-DRP ®

score of at least 80% or greater.

However, this DRP ® cutoff can be modified depending on the clinical outcome.

The study will be performed

in accordance with the Simon two-stage design (Simon 1989).

The patients will come to a screening visit within 2 weeks prior to first

administration of stenoparib.

Patients will receive a daily dose of 600 mg stenoparib as hard gelatin capsules administered in a 28-day

The treatment will continue until disease progression or unacceptable toxicity.

The clinical endpoint will be objective response

rate (ORR), as determined by RECIST 1.1.

Patients will continue the

treatment until the occurrence of:

(i) disease progression, or (ii) unacceptable toxicity, or (iii) patient refusal/withdrawing of consent,

or (iv) non-compliance to the protocol, or (v) physician decision to discontinue treatment, or treatment delay > 2 weeks (except in

the case of perceived patient benefit).

An End of Treatment visit will be conducted when administration of stenoparib is stopped.

with CR, PR or SD where treatment have been stopped will continue follow-up by phone every 12 weeks until death.

Anticipated clinical trials

sites and Principal Investigators would include Dr.

Dan Von Hoff (U.S.) and Dr.

Deb Sarker (UK).

Development for Additional

We have developed a protocol

for a Phase II, open label clinical study to investigate anti-tumor effect and tolerability of stenoparib in docetaxel-pre-treated metastatic

castration-resistant prostate cancer (mCRPC) patients selected by the Stenoparib-DRP ® companion diagnostic.

Patients would

receive 600 mg stenoparib as single oral agent in a 21-days cycle in in mCRPC patients who progressed on AR-targeted therapy (abiraterone

acetate, enzalutamide or investigational AR-targeted agent) and docetaxel-pre-treated metastatic castration-resistant prostate cancer

patients selected by the Stenoparib-DRP ® companion diagnostic.

Up to 30 mCRPC patients with predicted high probability

of response to stenoparib, as determined by a Stenoparib-DRP ® ) score of >80%, will be enrolled and treated.

effect of stenoparib is based on objective response rate defined as complete response (CR), partial response (PR) or stable disease (SD)

of > 9 weeks according to RECIST 1.1 for patients with measurable disease and defined as stable disease > 9 weeks including PSA

and bone metastases according to PCWG3.

This Phase II trial would likely have trial sites in the U.S.

and in the EU/Denmark.

DRP ® Companion Diagnostic for

We are developing stenoparib

together with its validated DRP ® companion diagnostic, which enables us to select the patients most likely to respond to

the drug in our clinical trials.

An Investigation Device Exemption (IDE) for our Stenoparib-DRP ® was granted by the FDA

(G180165) in 2018.

The Stenoparib-DRP ® , which comprises 414 expressed genes, was initially developed using a panel of 61

cancer cell lines (provided by Eisai) treated with stenoparib.

This putative DRP ® contains biomarkers that reflect the

mechanism of action of PARP and Tankyrase inhibition by stenoparib, as well as capturing much unknown tumor biology, and is largely independent

PARP inhibitors are designed to compete with NAD+ for the substrate binding to PARP and inhibit PARP activity.

Cells containing dysfunctional

BRCA1 or BRCA2 have been shown to become profoundly sensitized to the inhibition of PARP enzymatic activity, resulting in chromosomal

instability, cell cycle arrest and subsequent apoptosis.

PARP inhibition is thought to induce synthetic lethality, which describes a

process where at least two genetic lesions that individually are not lethal become lethal when combined in the same cell.

cells that are deficient in HR, which is not lethal in itself, are hypersensitive to a reduction in PARP activity by PARP inhibitors.

However, disruption to other proteins involved in HR DNA repair other than in BRCA may have the same effect on PARP inhibitor sensitivity.

further important mechanism of action for PARP inhibition is the trapping of the PARP1 and PARP2 enzymes at damaged DNA causing cytotoxicity

and cell death.

Recent studies have revealed a more complex web of fundamental cellular processes that PARP1 is involved in crucial cell

processes other than in DNA damage repair, such as chromatin remodeling and transcription or regulation of the cell cycle.

are multiple PARP inhibitors approved for either monotherapy or maintenance therapy or both in patients with advanced OC.

The effectiveness

of PARP inhibitors as monotherapy or as maintenance therapy has substantially improved the progression free survival and may be promising

for overall survival in OC patients.

PARP inhibitors as single agents or as potential enhancers of cytotoxic agents that provoke DNA

damage, such as alkylating agents and chemotherapy, have been investigated in a number of studies, including olaparib, rucaparib, niraparib,

veliparib, and talazoparib, where the two latter PARPi are still under development.

As of Q3 2022, PARP inhibitors were withdrawn from

the market for the treatment of active, advanced ovarian cancers.

is a current unmet need for treatment of patients with OC who have progressed on PARPi treatment.

Our ongoing Phase 2 study in ovarian

cancer allows for enrollment of patients previously treated with a PARPi.

We intend to use our Stenoparib-DRP ® to select

patients from this group that will have a high likelihood of responding to our PARPi, Stenoparib.

Opportunities & Development Plans for Stenoparib

of Pancreatic Ductal Adenocarcinoma (PDAC) & Rationale for Targeting PARP in PDAC

is the third leading cause of cancer related death in the United States (2018).

Initial presentation of the disease is typically with

metastasis, and the overall 5-year survival for all stages combined is 8%.

Molecular analysis has revealed four subtypes of PDAC giving

clinicians further insight into treating this deadly disease.

One subtype that has been elucidated and termed “unstable”

is significant for the presence of DNA damage repair deficiency and can be targeted by several old and emerging therapies.

One such therapy

that may be considered are PARP inhibitors.

have been reports of responses seen to PARP inhibitors in individuals with pancreatic cancer, and there are clinical trials currently

(NCT03140670, NCT02184195, NCT01585805) for this patient population.

One PARPi (olaparib) was approved by the FDA in December 2019 for

the treatment of BRCA1/2 mutated PDAC.

Due to the relatively common DNA repair pathway mutations in PDAC tumors, PARP inhibition may

be a potential therapeutic option in individuals with advanced PDAC with the HRD phenotype.

Companion Diagnostic for Stenoparib

are developing stenoparib together with its validated DRP ® companion diagnostic, which enables us to select the patients

most likely to respond to the drug in our clinical trials.

An IDE for our Stenoparib-DRP ® was granted by the FDA (G180165)

The Stenoparib-DRP ® , which comprises 414 expressed genes, was initially developed using a panel of 61 cancer

cell lines (provided by Eisai) treated with stenoparib.

This putative DRP ® contains biomarkers that reflect the mechanism

of action of PARP and Tankyrase inhibition by stenoparib, as well as capturing much unknown tumor biology, and is largely independent

of BRCA mutation.

The putative Stenoparib-DRP ® ,

developed through our DRP ® platform using gene expression data from cancer cell line testing data, was retrospectively

validated using biopsy materials from the Phase 1 trial of the drug (formerly E7449), sponsored by Eisai, that was conducted in the United

Kingdom (UK) from 2012-2015 (clinicaltrial.gov number NCT01618136).

Of 41 patients enrolled in the Phase 1 study, 35 had response assessment.

putative Stenoparib-DRP ® , developed through our DRP ® platform using gene expression data from cancer cell

line testing data, was retrospectively tested using biopsy materials from the Phase 1 trial of the drug (formerly E7449), sponsored by

Eisai, that was conducted in the United Kingdom (UK) from 2012-2015 (clinicaltrial.gov number NCT01618136).

Of 41 patients enrolled in

the Phase 1 study, 35 had response assessment.

Of these, 2 had PR (5% ORR) and 13 had SD.

Biopsies and BRCA analysis were voluntary and available from 16, and 7 patients, respectively.

Of the 16 patients with biopsies, 13 passed our QC in the lab and were assayed on the Affymetrix HG-U133Plus2 array.

A statistical analysis plan

was completed before initiation of retrospective blinded prediction of stenoparib sensitivity on the 13 samples.

Waterfall plot of 16 Phase 1 patients for which

biopsies were available

Before blinded retrospective

analysis of mixed histology biopsies from the Phase I trial of stenoparib, two crucial choices were made:

1) to use a reference population

of 819 breast cancer biopsies, and 2) to use as cutoff the population median of the Phase 1 biopsies.

Both choices turned out to be excellent,

because the population median of the Phase 1 biopsies was very close to the population median of the breast cancer reference population,

and when applied to the Phase 1 biopsies both medians separated the samples in identical populations with a clear difference in response

rate and PFS.

It was decided that the breast

cancer reference population with a cutoff of 50% would be used for the proposed Phase II trial.

This has the added advantage of being

the exact same parameters used for the blinded analysis of the Phase I trial.

The only difference is that DRP has been locked and retrospectively

validated between Phase I and proposed Phase II.

The following figure shows the unblinded comparison of dose-adjusted predicted sensitivity

to stenoparib and clinical response to stenoparib (the highest scoring SD patient is actually a long-term progression-free pancreatic

cancer survivor (still alive at last check at 406 days, and progression-free at last evaluation at 321 days):

Clinical performance of the Stenoparib-DRP ®

at the pre-specified cutoff of 50 in ovarian cancer

Ovarian only (N=3)

DRP ® positive (top 50%)

DRP ® negative (bottom 50%)

Biopsies and BRCA analysis were voluntary and

available from 16, and 7 patients, respectively.

Of the 16 patients with biopsies, 13 passed our QC in the lab and were assayed on the

Affymetrix HG-U133Plus2 array.

plot of 16 Phase 1 patients for which biopsies were available

statistical analysis plan was completed before initiation of retrospective blinded prediction of stenoparib sensitivity on the 13 samples.

blinded retrospective analysis of mixed histology biopsies from the Phase I trial of stenoparib, two crucial choices were made:

use a reference population of 819 breast cancer biopsies, and 2) to use as cutoff the population median of the Phase 1 biopsies.

choices turned out to be excellent, because the population median of the Phase 1 biopsies was very close to the population median of

the breast cancer reference population, and when applied to the Phase 1 biopsies both medians separated the samples in identical populations

with a clear difference in response rate and PFS.

was decided that the breast cancer reference population with a cutoff of 50% would be used for the proposed Phase II trial.

the added advantage of being the exact same parameters used for the blinded analysis of the Phase I trial.

The only difference is that

DRP has been locked and retrospectively validated between Phase I and proposed Phase II.

The following figure shows the unblinded comparison

of dose-adjusted predicted sensitivity to stenoparib and clinical response to stenoparib (the highest scoring SD patient is actually

a long-term progression-free pancreatic cancer survivor (still alive at last check at 406 days, and progression-free at last evaluation

at 321 days):

performance of the Stenoparib-DRP ® at the pre-specified cutoff of 50 in ovarian cancer

positive (top 50%)

negative (bottom 50%)

Overall precision:

1 unchanged sentence

100% of responders correctly predicted

100% of non-responders correctly predicted

Clinical performance of the Stenoparib-DRP ®

at the pre-specified cutoff of 50 for all histologies

All histologies (N=13)

DRP ® positive (top 50%)

DRP ® negative (bottom 50%)

Overall precision:

100% of non-responders correctly

performance of the Stenoparib-DRP ® at the pre-specified cutoff of 50 for all histologies

All histologies

positive (top 50%)

negative (bottom 50%)

69% correct prediction

1 unchanged sentence

64% of non-responders correctly predicted

The following figures show

Kaplan-Meier curves of overall survival (OS) and progression free survival (PFS) in two populations, those above a dose-adjusted cutoff

of 50 (N=6), and those below a cutoff of 50 (N=7).

The hazard ratio is 0.26 (P=0.04 one sided) and the median survival in the predicted

resistant group (below cutoff) is 208 days.

More than half of the patients remain alive in the group predicted sensitive.

Additionally, BRCA mutation

status considered, but was only available for 7 patients in the trial (NCT01618136), of which 6 are BRCA mutated.

Of these 6, 1 responded

to stenoparib, giving a response rate of 1/6 or 16% in the BRCA mutated population.

This equals the response rate observed in the unselected

13 patients analyzed with DRP ® score.

Thus, BRCA mutation does not appear to be a predictor of response in this small trial.

In sum, our retrospectively

validated Stenoparib-DRP ® companion diagnostic correctly identifies responder patients to stenoparib and we plan use this

DRP ® companion diagnostic for all of our clinical programs to advance stenoparib, including our ongoing Phase 2 ovarian

cancer study.

Existing PARP Inhibitors and Our Opportunity

Numerous PARP inhibitors,

including Lynparza ® (olaparib), Rubraca ® (rucaparib camsylate), Zejula ® (niraparib) and Talzenna ®

(talazoparib tosylate) have been approved by the FDA for multiple oncology indications, including ovarian, breast, prostate, and pancreatic

Sales of these FDA-approved PARP inhibitors were approximately $1.7 billion in 2019 and are forecasted to be over $7.0 billion

in 2025, with Lynparza (olaparib) accounting for $1.2 billion and over $4.0 billion in the 2019 and 2025 totals, respectively.

Despite the commercial success

of PARP inhibitors, broader adoption is limited by their high rates of GI and bone marrow toxicity which is largely a result of off-target

cell killing.

Adverse grade 3–4 events from this class of drugs include anemia, thrombocytopenia, neutropenia and alopecia.

common adverse reactions include nausea, vomiting, diarrhea, fatigue, and decreased appetite.

We believe Stenoparib is distinguished

among the PARP class of drugs by the following features and advantages:

It is a dual inhibitor of Tankyrases 1 and 2, which provides a likely dual cancer cell killing mechanism by interference with Wnt signaling pathways and chromosomal telomerase maintenance and stability.

It lacks myelotoxicity, a common limiting adverse event among PARP inhibitors, at the established MTD.

It is resistant to P-glycoprotein (PgP) mediated export from target cancer cells, resulting in higher accumulation of drug in target cells.

It can cross the Blood-Brain Barrier (BBB), enabling the potential treatment of primary brain tumors, such as glioblastoma multiforme (GBM), and brain metastases from other body tumors, such as malignant breast cancer.

Additionally, the use of our

Stenoparib-DRP ® companion diagnostic to identify and treat only those patients most likely to respond to the drug (while

excluding those patients most likely to be unresponsive to the drug), gives us a substantial advantage in increasing patient response

following figures show Kaplan-Meier curves of overall survival (OS) and progression free survival (PFS) in two populations, those above

a dose-adjusted cutoff of 50 (N=6), and those below a cutoff of 50 (N=7).

The hazard ratio is 0.26 (P=0.04 one sided) and the median

survival in the predicted resistant group (below cutoff) is 208 days.

More than half of the patients remain alive in the group predicted

Additionally,

BRCA mutation status was considered, but was only available for 7 patients in the trial (NCT01618136), of which 6 are BRCA mutated.

these 6, 1 responded to stenoparib, giving a response rate of 1/6 or 16% in the BRCA mutated population.

This equals the response rate

observed in the unselected 13 patients analyzed with DRP ® score.

Thus, BRCA mutation does not appear to be a predictor

of response in this small trial.

sum, our retrospectively tested Stenoparib-DRP ® companion diagnostic correctly identifies responder patients to stenoparib

and we plan use this DRP ® companion diagnostic for all of our clinical programs to advance stenoparib, including our ongoing

Phase 2 ovarian cancer study.

PARP Inhibitors and Our Opportunity

PARP inhibitors, including Lynparza ® (laparib), Rubraca ® (rucaparib camsylate), Zejula ®

(niraparib) and Talzenna ® (talazoparib tosylate) have been approved by the FDA for multiple oncology indications, including

ovarian, breast, prostate, and pancreatic cancer.

Sales of these FDA-approved PARP inhibitors were approximately $1.7 billion in 2019

and are forecasted to be over $7.0 billion in 2025, with Lynparza ® (laparib) accounting for $1.2 billion and over $4.0

billion in the 2019 and 2025 totals, respectively.

the commercial success of PARP inhibitors, broader adoption is limited by their high rates of GI and bone marrow/ myelo-toxicity, which

is largely a result of off-target cell killing.

Adverse grade 3–4 events from this class of drugs include anemia, thrombocytopenia,

neutropenia and alopecia.

Other common adverse reactions include nausea, vomiting, diarrhea, fatigue, and decreased appetite.

believe Stenoparib is distinguished among the PARP class of drugs by the following features and advantages:

It is a dual inhibitor

of Tankyrases 1 and 2, which provides a likely dual cancer cell killing mechanism by interference with Wnt signaling pathways and

chromosomal telomerase maintenance and stability.

It lacks myelotoxicity,

a common limiting adverse event among PARP inhibitors, at the established MTD.

It is resistant to P-glycoprotein

(PgP) mediated export from target cancer cells, resulting in higher accumulation of drug in target cells.

It can cross the BBB, enabling

the potential treatment of primary brain tumors, such as GBM, and brain metastases from other body tumors, such as malignant breast

Additionally,

the use of our Stenoparib-DRP ® companion diagnostic to identify and treat only those patients most likely to benefit from

the drug (while excluding those patients unlikely to benefit from the drug), gives us a substantial advantage in increasing patient benefit

rates, avoiding adverse events in patients that are not likely to benefit from our drug, and providing health economics advantages.

Furthermore, our DRP ®

for stenoparib identifies a broader group of potential responder patients than can be identified by the competitive biomarker approach

of only assessing BRCA 1 and 2 mutation status in order to select and treat patients.

The DRP ® for stenoparib comprises

414 genes, including Wnt-beta-catenin and a number of DNA repair pathways, and thus is a broader assessment of the tumor responsiveness

to the drug than determining mutation in one or two BRCA genes.

Overview of IXEMPRA ® (microtubule

Mechanisms of Action

Ixabepilone (IXEMPRA ® )

is a semisynthetic derivative of epothilone B, with improved in vitro metabolic stability.

It is a novel antineoplastic agent that stabilizes

microtubule dynamics, resulting in blockade of cancer cells in mitosis during cell division, leading to cell death.

Ixabepilone induces

a distinct pathway of cellular apoptosis via activation of caspase-2, whereas other tubulin agents, such as the taxanes, act via caspase-9.

Ixabepilone is a poor substrate for efflux transporters such as the multidrug resistance-related protein (MRP1) and P-glycoprotein (P-gp)

that are involved in drug-resistance mechanisms.

Epothilones have a tubulin-binding mode distinct from that of other microtubule- stabilizing

Ixabepilone’s tubulin-binding mode affects the microtubule dynamics of multiple ® -tubulin isoforms, including

the class III isoform of ® -tubulin ( ® -III tubulin), the expression of which has been implicated in clinical

taxane resistance.

As used in this section of this report describing our therapeutic candidate IXEMPRA ® , statements regarding

the use of our proprietary DRP ® companion diagnostics or our proprietary DRP ® platform or our observations

that our therapeutic candidate IXEMPRA ® may have anti-cancer or anti-tumor activity or is observed to be well tolerated

in a patient population should not be construed to mean that we have resolved all issues of safety and/or efficacy for our therapeutic

candidate IXEMPRA ® or our putative IXEMPRA ® -DRP ® companion diagnostic.

Issues of safety and

efficacy for any therapeutic candidate or companion diagnostic may only be determined by the U.S.

FDA or other applicable regulatory authorities

in jurisdictions outside the United States.

Ixabepilone has anti-tumor

activity in vivo against a broad spectrum of tumor types, including tumors that overexpress P-gp and are resistant to multiple agents

including taxanes, anthracyclines, and vinca alkaloids.

Ixabepilone demonstrated synergistic in vivo activity in combination with capecitabine.

our DRP ® for stenoparib identifies a broader group of potential responder patients than can be identified by the competitive

biomarker approach of only assessing BRCA 1 and 2 mutation status in order to select and treat patients.

The DRP ® for

stenoparib comprises 414 genes, including Wnt-beta-catenin and a number of DNA repair pathways, and thus is a broader assessment of the

tumor responsiveness to the drug than determining mutation in one or two BRCA genes.

Therapeutic Programs Now De-prioritized or Terminated

changes to Allarity senior management were instituted in December 2023.

Under the leadership of the newly appointed interim CEO, Thomas

Jensen, significant changes are being implemented currently to align the business with current fiscal realities and to focus company

resources on Stenoparib, the company’s most promising clinical asset.

Given that this leadership change is so recent, the following

sections for the 10K are still included for reference even though the further development of these assets is paused or terminated.

of IXEMPRA ® (microtubule inhibitor) - Deprioritized

(IXEMPRA ® ) is a semisynthetic derivative of epothilone B, with improved in vitro metabolic stability.

It is a novel antineoplastic

agent that stabilizes microtubule dynamics, resulting in blockade of cancer cells in mitosis during cell division, leading to cell death.

Ixabepilone induces a distinct pathway of cellular apoptosis via activation of caspase-2, whereas other tubulin agents, such as the taxanes,

act via caspase-9.

Ixabepilone is a poor substrate for efflux transporters such as the multidrug resistance-related protein (MRP1) and

P-glycoprotein (P-gp) that are involved in drug-resistance mechanisms.

Epothilones have a tubulin-binding mode distinct from that of

other microtubule- stabilizing agents.

Ixabepilone’s tubulin-binding mode affects the microtubule dynamics of multiple ® -tubulin

isoforms, including the class III isoform of ® -tubulin ( ® -III tubulin), the expression of which has been

implicated in clinical taxane resistance.

As used in this section of this report describing our therapeutic candidate IXEMPRA ® ,

statements regarding the use of our proprietary DRP ® companion diagnostics or our proprietary DRP ® platform

or our observations that our therapeutic candidate IXEMPRA ® may have anti-cancer or anti-tumor activity or is observed

to be well tolerated in a patient population should not be construed to mean that we have resolved all issues of safety and/or efficacy

for our therapeutic candidate IXEMPRA ® or our putative IXEMPRA ® -DRP ® companion diagnostic.

Issues of safety and efficacy for any therapeutic candidate or companion diagnostic may only be determined by the U.S.

FDA or other applicable

regulatory authorities in jurisdictions outside the United States.

has anti-tumor activity in vivo against a broad spectrum of tumor types, including tumors that overexpress P-gp and are resistant to

multiple agents including taxanes, anthracyclines, and vinca alkaloids.

Ixabepilone demonstrated synergistic in vivo activity in combination

with capecitabine.

In addition to direct anti-tumor activity, ixabepilone demonstrated antiangiogenic activity in vivo.

The nonclinical pharmacokinetic

(PK) studies performed with ixabepilone were directed toward the preliminary assessment of the absorption, distribution, metabolism, and

excretion of the drug.

Ixabepilone was (a) orally bioavailable with bioavailability ranging from 8 to 40% in mice, rats, and dogs;

nonclinical pharmacokinetic (PK) studies performed with ixabepilone were directed toward the preliminary assessment of the absorption,

distribution, metabolism, and excretion of the drug.

Ixabepilone was (a) orally bioavailable with bioavailability ranging from 8

to 40% in mice, rats, and dogs;

(b) extensively distributed extravascularly;

(d) extensively metabolized to many metabolites

and the metabolite profile was similar among species including humans;

(d) extensively

metabolized to many metabolites and the metabolite profile was similar among species including humans;

I metabolized by CYP3A4/5;

(f) cleared primarily via oxidative

metabolism and then mostly excreted in the feces;

(g) neither a CYP inhibitor nor a CYP inducer at clinically relevant concentrations.

Pre-Clinical Studies

The results from the in vitro

cytotoxicity studies against extensive panels of human-tissue specific, taxane-sensitive and taxane-resistant (including MDR, ® -III

tubulin over- expression, and tubulin mutation mechanisms), cancer cell lines demonstrate that ixabepilone has potent and broad-spectrum

antineoplastic activity.

The effectiveness of ixabepilone in vitro is paralleled by equally broad-spectrum activity observed in vivo.

Ixabepilone demonstrated a broad spectrum of in vivo anti-tumor activity in taxane- sensitive and taxane-resistant human cancer xenograft

Less frequent dosing schedules allowed higher doses of ixabepilone to be given and performed better than the more frequent dosing

Against a total of 35 human tumor xenografts grown in mice, representing a wide array of tumor types, ixabepilone demonstrated

anti-tumor activities, producing 1 LCK or greater anti-cancer activity in 33 of 35 tumors.

Ixabepilone demonstrated the ability to overcome

drug resistance due to the Pgp-mediated multidrug resistance (MDR) phenotype in vivo, reversing the MDR resistance of 2 established MDR

cleared primarily via oxidative metabolism and then mostly excreted in the feces;

(g) neither a CYP inhibitor nor a CYP inducer at clinically

relevant concentrations.

results from the in vitro cytotoxicity studies against extensive panels of human-tissue specific, taxane-sensitive and taxane-resistant

(including MDR, ® -III tubulin over- expression, and tubulin mutation mechanisms), cancer cell lines demonstrate that ixabepilone

has potent and broad-spectrum antineoplastic activity.

The effectiveness of ixabepilone in vitro is paralleled by equally broad-spectrum

activity observed in vivo.

Ixabepilone demonstrated a broad spectrum of in vivo anti-tumor activity in taxane- sensitive and taxane-resistant

human cancer xenograft models.

Less frequent dosing schedules allowed higher doses of ixabepilone to be given and performed better than

the more frequent dosing schedules.

Against a total of 35 human tumor xenografts grown in mice, representing a wide array of tumor types,

ixabepilone demonstrated anti-tumor activities, producing 1 LCK or greater anti-cancer activity in 33 of 35 tumors.

Ixabepilone demonstrated

the ability to overcome drug resistance due to the Pgp-mediated multidrug resistance (MDR) phenotype in vivo, reversing the MDR resistance

of 2 established MDR models:

the 16C/ADR breast carcinoma models and the HCT116/VM46 human colon carcinoma model.

Ixabepilone also demonstrated anti-tumor

activity both in vitro and in vivo against a human tumor model that over expresses MRP1 (Pat-7), producing in vitro IC90 values of 7.4

nM (compared with 150 nM for paclitaxel) and an in vivo activity of 2.9 LCK (compared with 0.8 LCK for paclitaxel).

Ixabepilone suppresses the

dynamic instability of < ® -III microtubules and< ® -II microtubules.

This is in contrast to paclitaxel

which had no suppressive effect on the dynamic instability of < ® -III microtubules, but suppressed the dynamic instability

of < ® -II microtubules.

Thus, ixabepilone should be more effective than paclitaxel at inhibiting proper formation of

the mitotic spindle and disrupting mitosis in tumor cells with high expression of ® -III tubulin.

On this basis, ixabepilone

is expected to be more active on tumors that are resistant to paclitaxel because of over expression of ® -III tubulin.

The in vitro and in vivo cardiovascular

safety pharmacology studies conducted with ixabepilone indicated that it is unlikely that ixabepilone will affect electrocardiographic

parameters at anticipated plasma concentrations in patients.

Ixabepilone induced drug- related clinical signs consistent with peripheral

neuropathy in rodents.

In a comparative study in rats, ixabepilone and paclitaxel induced peripheral neuropathy that was similar in nature

and characterized by decreases in sensory and motor maximal nerve conduction velocities and reductions in sensory and compound nerve-response

Ixabepilone also demonstrated

anti-tumor activity both in vitro and in vivo against a human tumor model that over expresses MRP1 (Pat-7), producing in vitro IC90 values

of 7.4 nM (compared with 150 nM for paclitaxel) and an in vivo activity of 2.9 LCK (compared with 0.8 LCK for paclitaxel).

suppresses the dynamic instability of < ® -III microtubules and< ® -II microtubules.

This is in contrast

to paclitaxel which had no suppressive effect on the dynamic instability of < ® -III microtubules, but suppressed the

dynamic instability of < ® -II microtubules.

Thus, ixabepilone should be more effective than paclitaxel at inhibiting

proper formation of the mitotic spindle and disrupting mitosis in tumor cells with high expression of ® -III tubulin.

this basis, ixabepilone is expected to be more active on tumors that are resistant to paclitaxel because of over expression of ® -III

in vitro and in vivo cardiovascular safety pharmacology studies conducted with ixabepilone indicated that it is unlikely that ixabepilone

will affect electrocardiographic parameters at anticipated plasma concentrations in patients.

Ixabepilone induced drug- related clinical

signs consistent with peripheral neuropathy in rodents.

In a comparative study in rats, ixabepilone and paclitaxel induced peripheral

neuropathy that was similar in nature and characterized by decreases in sensory and motor maximal nerve conduction velocities and reductions

in sensory and compound nerve-response amplitudes.

There were no ixabepilone-related CNS or respiratory findings.

The combination of ixabepilone

with a number of approved anticancer therapeutic agents produced anti-tumor activities that were markedly greater than the best achievable

responses from the individual single agents administered at their MTD alone.

Such therapeutic synergism was observed with capecitabine,

cetuximab, bevacizumab, or trastuzumab.

Modest anti-cancer activity enhancement was observed when combined with irinotecan.

therapeutic advantage was observed when combined with gefitinib, gemcitabine, or paclitaxel).

The pharmacokinetic characteristics

of ixabepilone in mice, rats, and dogs are comparable to those in humans, indicating the acceptability of those species for the toxicological

assessment of ixabepilone.

Serum protein binding of ixabepilone was moderate in rat, dog, and human serum.

In both animals and humans,

ixabepilone was extensively metabolized via oxidative metabolism and eliminated mainly through fecal excretion.

Only metabolites formed

through oxidation of ixabepilone were found in animals and humans.

All of the metabolites identified in humans were present in the species

used in the toxicological evaluation of ixabepilone.

The total amount of metabolites, as a percentage of the total radioactive dose in

excreta (urine and feces), was high in all species studied.

The known degradants of ixabepilone, BMS-249798, BMS-326412, and BMS-567637,

were detected in plasma and excreta across species.

The metabolite and degradant profiles in plasma are similar among humans, rats, and

dogs, with unchanged ixabepilone being the most abundant drug-related component.

Although the pharmacologic activity of individual metabolites

is not known, a mixture of in vitro metabolites of ixabepilone was not active in in vitro cytotoxicity assays.

Ixabepilone is a substrate

of CYP3A4 and CYP3A5.

The PK of ixabepilone may be affected by the co-administration of agents that inhibit or induce CYP3A4.

is an inhibitor of CYP3A4, but it does not inhibit any of the other common CYP enzymes.

Ixabepilone is not an inducer of CYP enzymes in

Based on the efficacious plasma concentration and the in vitro inhibition and induction characteristics, ixabepilone is not expected

to affect the PK of co-administered agents that are metabolized by CYP enzymes.

Nonclinical toxicity studies

identified the principal target-organ, genetic, and developmental toxicities of ixabepilone.

Ixabepilone principally affected tissues

having rapid-cell division, including the GI, hematopoietic and lymphoid systems, and the male reproductive system.

In mice and rats,

peripheral neuropathy was also a prominent effect.

Ixabepilone-induced toxicities were generally reversible following a 1-month, post

dose recovery period, except for delayed testicular effects in rats and dogs and peripheral neuropathy in rats and mice.

In rats, females

were generally more severely affected than males, consistent with higher systemic exposures in females.

When administered daily for 2

weeks or once every 21 days for 6 or 9 months, ixabepilone toxicity was similar to that observed in the single-dose, 5-day, and 1-month

intermittent dose (QWx5) toxicity studies, with the exception of loss of bony trabeculae of the femoral growth plate in rats, which was

not seen in any other studies.

The increased growth-plate thickness observed in the rat is not likely to be a safety risk for the treatment

of cancer in adult human populations, because in the rat, unlike humans, the growth plates do not fuse upon reaching sexual maturity.

Ixabepilone was not mutagenic

in the Ames bacterial mutation assay.

Ixabepilone was not clastogenic in the in vitro cytogenetics assay in primary human lymphocytes,

but did increase the incidence of polyploid lymphocytes at high concentrations.

However, ixabepilone was clastogenic (induction of micronuclei)

in the in vivo rat micronucleus study.

These findings were similar to other microtubule-stabilizing drugs and result in a benefit-risk

analysis in the indicated patient population that supports the use of these drugs for a cancer indication.

Ixabepilone did not affect

mating or fertility in a rat reproduction study, and induced embryo-fetal toxicity in rats and rabbits only at doses that also caused

maternal toxicity.

Since clinical administration of ixabepilone occurs at doses associated with minimal to mild clinical side effects,

administration during pregnancy may pose a risk for fetal toxicity.

The single- and repeat-dose

IV toxicity studies with ixabepilone adequately predicted the clinical toxicities that were subsequently observed in humans.

In both experimental

animals and humans, ixabepilone toxicities were primarily manifested in the GI, hematopoietic, and peripheral nervous systems.

These effects

were expected and consistent with the toxicity produced by other microtubule-stabilizing anticancer drugs.

In general, the nonclinical

species were more sensitive to ixabepilone-induced toxicity than human subjects.

In vitro, vincristine and paclitaxel were more potent

than ixabepilone in inhibiting mitochondrial axonal transport in fetal dorsal root ganglion culture, whereas in mice and rats, paclitaxel

and ixabepilone induced axonal degeneration or decreases in nerve conduction velocities that were similar in nature and severity.

on the intended use of ixabepilone in treating advanced breast cancer and other solid tumors, the scope and results of the nonclinical

pharmacology, pharmacokinetics, toxicity, and exposure studies support the continuous IV administration of ixabepilone on a once every

21-day cycle in this patient population.

Prior Clinical Trials

Ixabepilone (IXEMPRA ® )

combination of ixabepilone with a number of approved anticancer therapeutic agents produced anti-tumor activities that were markedly

greater than the best achievable responses from the individual single agents administered at their MTD alone.

Such therapeutic synergism

was observed with capecitabine, cetuximab, bevacizumab, or trastuzumab.

Modest anti-cancer activity enhancement was observed when combined

with irinotecan.

However, no therapeutic advantage was observed when combined with gefitinib, gemcitabine, or paclitaxel).

pharmacokinetic characteristics of ixabepilone in mice, rats, and dogs are comparable to those in humans, indicating the acceptability

of those species for the toxicological assessment of ixabepilone.

Serum protein binding of ixabepilone was moderate in rat, dog, and

both animals and humans, ixabepilone was extensively metabolized via oxidative metabolism and eliminated mainly through fecal excretion.

Only metabolites formed through oxidation of ixabepilone were found in animals and humans.

All of the metabolites identified in humans

were present in the species used in the toxicological evaluation of ixabepilone.

The total amount of metabolites, as a percentage of

the total radioactive dose in excreta (urine and feces), was high in all species studied.

The known degradants of ixabepilone, BMS-249798,

BMS-326412, and BMS-567637, were detected in plasma and excreta across species.

The metabolite and degradant profiles in plasma are similar

among humans, rats, and dogs, with unchanged ixabepilone being the most abundant drug-related component.

Although the pharmacologic activity

of individual metabolites is not known, a mixture of in vitro metabolites of ixabepilone was not active in in vitro cytotoxicity assays.

is a substrate of CYP3A4 and CYP3A5.

The PK of ixabepilone may be affected by the co-administration of agents that inhibit or induce

Ixabepilone is an inhibitor of CYP3A4, but it does not inhibit any of the other common CYP enzymes.

Ixabepilone is not an inducer

of CYP enzymes in vitro.

Based on the efficacious plasma concentration and the in vitro inhibition and induction characteristics, ixabepilone

is not expected to affect the PK of co-administered agents that are metabolized by CYP enzymes.

toxicity studies identified the principal target-organ, genetic, and developmental toxicities of ixabepilone.

Ixabepilone principally

affected tissues having rapid-cell division, including the GI, hematopoietic and lymphoid systems, and the male reproductive system.

In mice and rats, peripheral neuropathy was also a prominent effect.

Ixabepilone-induced toxicities were generally reversible following

a 1-month, post dose recovery period, except for delayed testicular effects in rats and dogs and peripheral neuropathy in rats and mice.

In rats, females were generally more severely affected than males, consistent with higher systemic exposures in females.

When administered

daily for 2 weeks or once every 21 days for 6 or 9 months, ixabepilone toxicity was similar to that observed in the single-dose, 5-day,

and 1-month intermittent dose (QWx5) toxicity studies, with the exception of loss of bony trabeculae of the femoral growth plate in rats,

which was not seen in any other studies.

The increased growth-plate thickness observed in the rat is not likely to be a safety risk for

the treatment of cancer in adult human populations, because in the rat, unlike humans, the growth plates do not fuse upon reaching sexual

was not mutagenic in the Ames bacterial mutation assay.

Ixabepilone was not clastogenic in the in vitro cytogenetics assay in primary

human lymphocytes, but did increase the incidence of polyploid lymphocytes at high concentrations.

However, ixabepilone was clastogenic

(induction of micronuclei) in the in vivo rat micronucleus study.

These findings were similar to other microtubule-stabilizing drugs

and result in a benefit-risk analysis in the indicated patient population that supports the use of these drugs for a cancer indication.

Ixabepilone did not affect mating or fertility in a rat reproduction study, and induced embryo-fetal toxicity in rats and rabbits only

at doses that also caused maternal toxicity.

Since clinical administration of ixabepilone occurs at doses associated with minimal to

mild clinical side effects, administration during pregnancy may pose a risk for fetal toxicity.

single- and repeat-dose IV toxicity studies with ixabepilone adequately predicted the clinical toxicities that were subsequently observed

In both experimental animals and humans, ixabepilone toxicities were primarily manifested in the GI, hematopoietic, and peripheral

nervous systems.

These effects were expected and consistent with the toxicity produced by other microtubule-stabilizing anticancer drugs.

In general, the nonclinical species were more sensitive to ixabepilone-induced toxicity than human subjects.

In vitro, vincristine and

paclitaxel were more potent than ixabepilone in inhibiting mitochondrial axonal transport in fetal dorsal root ganglion culture, whereas

in mice and rats, paclitaxel and ixabepilone induced axonal degeneration or decreases in nerve conduction velocities that were similar

in nature and severity.

Based on the intended use of ixabepilone in treating advanced breast cancer and other solid tumors, the scope

and results of the nonclinical pharmacology, pharmacokinetics, toxicity, and exposure studies support the continuous IV administration

of ixabepilone on a once every 21-day cycle in this patient population.

Clinical Trials

was originally developed through Phase 3 clinical trials and brought to market by Bristol-Myers Squibb (BMS).

In Phase 1 clinical trials

of ixabepilone as monotherapy, objective responses were demonstrated in a variety of tumor types, including breast, colon, head and neck,

ovarian, endometrial, vulvar, and peritoneal cancers, melanoma, and non-Hodgkin’s lymphoma.

Dose-limiting toxicities observed

in Phase 1 clinical trials of ixabepilone as monotherapy included sensory neuropathy, neutropenia, myalgia, and fatigue.

Adverse events

(AEs) reported in Phase 1 studies in which ixabepilone was used in combination with other chemotherapy agents ( e.g ., carboplatin

[CA163007], doxorubicin [CA163008], and irinotecan [CA163025]) were similar qualitatively and in frequency to that observed in monotherapy

In Phase 1 clinical

trials of ixabepilone as monotherapy, objective responses were demonstrated in a variety of tumor types, including breast, colon, head

and neck, ovarian, endometrial, vulvar, and peritoneal cancers, melanoma, and non-Hodgkin’s lymphoma.

Dose-limiting

toxicities observed in Phase 1 clinical trials of ixabepilone as monotherapy included sensory neuropathy, neutropenia, myalgia, and fatigue.

Adverse events (AEs) reported in Phase 1 studies in which ixabepilone was used in combination with other chemotherapy agents ( e.g .,

carboplatin [CA163007], doxorubicin [CA163008], and irinotecan [CA163025]) were similar qualitatively and in frequency to that observed

in monotherapy studies;

no toxicities unique to combination therapies were reported.

The PK of ixabepilone are

linear, based on consistent total body clearance and apparent terminal elimination half-life across doses from 15 mg/m 2 to

PK of ixabepilone are linear, based on consistent total body clearance and apparent terminal elimination half-life across doses from

15 mg/m 2 to 57 mg/m 2 .

The coadministration of ketoconazole increases ixabepilone exposure in patients.

Ketoconazole or other potent CYP3A4

inhibitors such as itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir,

nelfinavir, delavirdine, or voriconazole should be avoided.

If alternative treatment cannot be administered, a dose adjustment should

be considered, and patients should be monitored closely for acute toxicities.

Pharmacokinetics results indicate that exposure to ixabepilone

is increased by 22%, 30%, and 81% in patients with mild, moderate, or severe hepatic dysfunction, respectively.

After coadministration

of ixabepilone and capecitabine, PK differences are minor and are not expected to affect the toleration profile or anti-cancer activity

of either ixabepilone or capecitabine.

In a Pha½1/2 clinical

trial (CA163031) evaluating ixabepilone in combination with capecitabine for the treatment of metastatic breast cancer (MBC), common toxicities

included fatigue, nausea, hand-foot syndrome, and sensory neuropathy.

Phase 2 clinical trials demonstrated

the activity of ixabepilone in advanced breast cancer, non- small cell, small-cell lung cancers, prostate cancer, gastric, and other malignancies.

The most notable toxicities reported in Phase 2 trials of ixabepilone as monotherapy are peripheral neuropathy, neutropenia, myalgia,

arthralgia, alopecia, and fatigue.

The peripheral neuropathy has been predominantly sensory, cumulative in nature, and reversible upon

discontinuation of ixabepilone.

In a large, international

Phase 3 clinical trial (CA16304612) in patients with taxane-resistant and anthracycline-pre-treated or resistant metastatic or locally

advanced breast cancer, ixabepilone in combination with capecitabine resulted in a statistically significant improvement in progression-free

survival (PFS) and response rate (RR) compared to capecitabine monotherapy, per the independent radiology review committee (IRRC).

similar, large, multicenter, international randomized, Phase 3 clinical trial (CA16304813) compared ixabepilone in combination with capecitabine

to capecitabine alone in patients with metastatic or locally advanced breast cancer previously treated with anthracyclines and taxanes.

CA163048, in which OS was the primary endpoint, demonstrated statistically significant and clinically meaningful superiority in PFS and

improved RR over capecitabine alone that translated into a modest improvement in overall survival (OS) favoring the combination which

did not meet statistical significance.

These studies were conducted in 29 countries, with more than 300 clinical investigators and over

1,200 treated patients.

or other potent CYP3A4 inhibitors such as itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir,

amprenavir, indinavir, nelfinavir, delavirdine, or voriconazole should be avoided.

If alternative treatment cannot be administered, a

dose adjustment should be considered, and patients should be monitored closely for acute toxicities.

Pharmacokinetics results indicate

that exposure to ixabepilone is increased by 22%, 30%, and 81% in patients with mild, moderate, or severe hepatic dysfunction, respectively.

After coadministration of ixabepilone and capecitabine, PK differences are minor and are not expected to affect the toleration profile

or anti-cancer activity of either ixabepilone or capecitabine.

a Phase 1/2 clinical trial (CA163031) evaluating ixabepilone in combination with capecitabine for the treatment of metastatic breast

cancer (MBC), common toxicities included fatigue, nausea, hand-foot syndrome, and sensory neuropathy.

2 clinical trials demonstrated the activity of ixabepilone in advanced breast cancer, non- small cell, small-cell lung cancers, prostate

cancer, gastric, and other malignancies.

The most notable toxicities reported in Phase 2 trials of ixabepilone as monotherapy are peripheral

neuropathy, neutropenia, myalgia, arthralgia, alopecia, and fatigue.

The peripheral neuropathy has been predominantly sensory, cumulative

in nature, and reversible upon discontinuation of ixabepilone.

a large, international Phase 3 clinical trial (CA16304612) in patients with taxane-resistant and anthracycline-pre-treated or resistant

metastatic or locally advanced breast cancer, ixabepilone in combination with capecitabine resulted in a statistically significant improvement

in progression-free survival (PFS) and response rate (RR) compared to capecitabine monotherapy, per the independent radiology review

committee (IRRC).

Another similar, large, multicenter, international randomized, Phase 3 clinical trial (CA16304813) compared ixabepilone

in combination with capecitabine to capecitabine alone in patients with metastatic or locally advanced breast cancer previously treated

with anthracyclines and taxanes.

CA163048, in which OS was the primary endpoint, demonstrated statistically significant and clinically

meaningful superiority in PFS and improved RR over capecitabine alone that translated into a modest improvement in overall survival (OS)

favoring the combination which did not meet statistical significance.

These studies were conducted in 29 countries, with more than 300

clinical investigators and over 1,200 treated patients.

The studies included dozens of trial sites spread throughout European countries.

Based on the Phase 3 clinical

trials, ixabepilone was approved by the FDA in 2007 for the treatment of metastatic breast cancer in the following settings:

In combination with capecitabine for the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline and a taxane.

As monotherapy for the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline, a taxane, and capecitabine.

Despite the positive Phase

3 clinical trial results leading to approval of Ixabepilone in the U.S., the drug has not yet been approved in Europe, due to the EMA’s

determination of insufficient risk-benefit for Ixabepilone under the European socialized medicine pricing structure.

Subsequently, IXEMPRA ®

was out-licensed to us to pursue approval in Europe using our IXEMPRA ® -DRP ® -selected patient population

in order to show statistical significance in further clinical trials that the therapeutic candidate has sufficient risk-benefit under

European standards to support a pricing structure that would be appropriate.

As of March 2009, more than

3,144 patients have been treated with ixabepilone in BMS- sponsored Phase 1, 2, and 3 clinical trials.

In addition, the Cancer Therapy

Evaluation Program (CTEP) program of the U.S.

National Cancer Institute (NCI) independently conducted a number of clinical studies.

studies demonstrated the activity of ixabepilone in a variety of tumor types, including breast, hormone-refractory prostate, pancreatic,

renal cell, non-small cell and small-cell lung cancers, and non-Hodgkin’s lymphoma.

DRP ® -Guided Phase 2 Clinical

We are currently conducting

a DRP ® -guided, Phase 2, open label, single arm clinical trial — in Europe — to investigate the toleration and

anti-cancer activity of IXEMPRA ® as monotherapy in patients with metastatic or locally advanced breast cancer after failure

of an anthracycline, a taxane, and capecitabine.

on the Phase 3 clinical trials, ixabepilone was approved by the FDA in 2007 for the treatment of metastatic breast cancer in the following

combination with capecitabine for the treatment of metastatic or locally advanced breast

cancer in patients after failure of an anthracycline and a taxane.

monotherapy for the treatment of metastatic or locally advanced breast cancer in patients

after failure of an anthracycline, a taxane, and capecitabine.

the positive Phase 3 clinical trial results leading to approval of Ixabepilone in the U.S., the drug has not yet been approved in Europe,

due to the EMA’s determination of insufficient risk-benefit for Ixabepilone under the European socialized medicine pricing structure.

Subsequently, IXEMPRA ® was out-licensed to us to pursue approval in Europe using our IXEMPRA ® -DRP ® -selected

patient population in order to show statistical significance in further clinical trials that the therapeutic candidate has sufficient

risk-benefit under European standards to support a pricing structure that would be appropriate.

of March 2009, more than 3,144 patients have been treated with ixabepilone in BMS- sponsored Phase 1, 2, and 3 clinical trials.

the Cancer Therapy Evaluation Program (CTEP) program of the U.S.

National Cancer Institute (NCI) independently conducted a number of

clinical studies.

These studies demonstrated the activity of ixabepilone in a variety of tumor types, including breast, hormone-refractory

prostate, pancreatic, renal cell, non-small cell and small-cell lung cancers, and non-Hodgkin’s lymphoma.

DRP ® -Guided

Phase 2 Clinical Trial

are currently conducting a DRP ® -guided, Phase 2, open label, single arm clinical trial — in Europe — to investigate

the toleration and anti-cancer activity of IXEMPRA ® as monotherapy in patients with metastatic or locally advanced breast

cancer after failure of an anthracycline, a taxane, and capecitabine.

This clinical trial, with an enrollment target of 60 IXEMPRA ® -DRP ® -selected

1 unchanged sentence

Patients are selected

by using the putative IXEMPRA ® -DRP ® companion diagnostic at a cut-off score of sixty-seven percent (67%),

and IXEMPRA ® is administered at 40 mg/m 2 infused intravenously over 3 hours every 3 weeks (in accordance with

label of the drug).

by using the putative IXEMPRA ® -DRP ® companion diagnostic at a cut-off score of 67%, and IXEMPRA ®

is administered at 40 mg/m 2 infused intravenously over 3 hours every 3 weeks (in accordance with the U.S.

Dose reduction is required in certain patients with elevated AST, ALT, or bilirubin.

The trial was initiated

in April 2021.

Thus far, several DRP ® -selected patients have been enrolled and dosed in the trial, despite delays resulting

from the ongoing COVID-19 pandemic.

The clinical trial’s goal is to provide a superior clinical benefit to DRP ® -selected

patients receiving IXEMPRA ® , as compared to historical clinical data from breast cancer patients treated with IXEMPRA ®

The trial was initiated in April 2021.

far, several DRP ® -selected patients have been enrolled and dosed in the trial, despite delays resulting from the ongoing

COVID-19 pandemic.

The clinical trial’s goal is to provide a superior clinical benefit to DRP ® -selected patients

receiving IXEMPRA ® , as compared to historical clinical data from breast cancer patients treated with IXEMPRA ®

but not selected with the putative DRP ® companion diagnostic for the drug.

3 unchanged sentences

Research International, our CRO for the Phase 2 clinical trial, where Smerud has agreed to accept a single digit share of any proceeds

we generate from the commercialization or disposition of IXEMPRA ® in exchange for the anticipated costs our CRO would incur

in conducting the Phase 2 clinical trial up to an agreed upon maximum amount of costs incurred.

Overview of Metastatic Breast Cancer

Breast cancer is the most

frequent malignancy in women worldwide, and the second most common cancer worldwide, with an estimated 1.8 million new diagnoses per year.

we generate from the commercialization or disposition of IXEMPRA ® in exchange for the anticipated costs our CRO would

incur in conducting the Phase 2 clinical trial up to an agreed upon maximum amount of costs incurred.

of Metastatic Breast Cancer

cancer is the most frequent malignancy in women worldwide, and the second most common cancer worldwide, with an estimated 1.8 million

new diagnoses per year.

In the U.S., breast cancer has the highest prevalence among all cancers.

The Surveillance, Epidemiology, and End Results (“SEER”)

Program at National Cancer Institute estimates that in 2020, there will be 276,000 new cases of breast cancer in the U.S.

alone, and more

than 40,000 deaths.

Treatment options for breast cancer depend on many factors, including the stage of cancer.

Breast cancer is a heterogeneous

disease which is grouped into several clinical subtypes based on the expression of three proteins:

ER, progesterone receptor (“PR”)

Both ER and PR are hormone receptors, and tumors that express either of these receptors are referred to as hormone receptor-positive.

The American Cancer Society estimates that approximately 75-80% of all breast cancers express estrogen receptor (“ER+”) highlighting

the central role of ER signaling in driving a large majority of breast cancer.

Although early-stage non-metastatic disease is curable

in approximately 70-80% of patients, advanced breast cancer with distant organ metastases is considered incurable with currently available

Advanced breast cancer comprises inoperable locally advanced breast cancer, which has not spread to distant organs, and metastatic

(stage IV) breast cancer;

common sites of spread are bone, lungs, liver, and brain.

Currently, it is a treatable but virtually incurable

disease, with metastases including to the brain being the cause of death in almost all patients, and a median overall survival of two

to three years.

Patients with metastatic breast cancer receive treatments that aim to relieve their symptoms and to prolong quality-adjusted

life expectancy.

Treatment often continues

until the cancer starts growing again or until side effects become unacceptable.

If this happens, other drugs might be tried.

of drugs used for stage IV (metastatic) breast cancer depend on the hormone receptor status and the HER2 status of the cancer.

hormone receptor-positive (estrogen receptor-positive or progesterone receptor-positive) cancers are often treated first with hormone

therapy (tamoxifen or an aromatase inhibitor).

This may be combined with a targeted drug such as a CDK4/6 inhibitor, everolimus or a PI3K

Women who haven’t yet gone through menopause are often treated with tamoxifen or with medicines that keep the ovaries

from making hormones along with other drugs.

Because hormone therapy can take months to work, chemo is often the first treatment for patients

with serious problems from their cancer spread, such as breathing problems.

Chemotherapy is the main treatment for women with hormone

receptor-negative (ER-negative and PR-negative) cancers.

These breast cancers are either HER2 positive or triple negative.

Trastuzumab (Herceptin ® )

may help women with HER2-positive cancers live longer if it’s given along with chemo or with other medications such as hormonal

therapy or other anti-HER2 drugs.

Pertuzumab (Perjeta ® ), another targeted drug, might be added as well.

Other options might

include targeted drugs such as lapatinib (which may be given with certain chemo drugs or hormone therapy) or ado-trastuzumab emtansine

(Kadcyla ® ).

The Surveillance, Epidemiology, and

End Results (“SEER”) Program at National Cancer Institute estimates that in 2020, there will be 276,000 new cases of breast

cancer in the U.S.

alone, and more than 40,000 deaths.

Treatment options for breast cancer depend on many factors, including the stage

Breast cancer is a heterogeneous disease which is grouped into several clinical subtypes based on the expression of three

ER, progesterone receptor (“PR”) and HER2.

Both ER and PR are hormone receptors, and tumors that express either

of these receptors are referred to as hormone receptor-positive.

The American Cancer Society estimates that approximately 75-80% of all

breast cancers express estrogen receptor (“ER+”) highlighting the central role of ER signaling in driving a large majority

of breast cancer.

Although early-stage non-metastatic disease is curable in approximately 70-80% of patients, advanced breast cancer

with distant organ metastases is considered incurable with currently available therapies.

Advanced breast cancer comprises inoperable

locally advanced breast cancer, which has not spread to distant organs, and metastatic (stage IV) breast cancer;

common sites of spread

are bone, lungs, liver, and brain.

Currently, it is a treatable but virtually incurable disease, with metastases including to the brain

being the cause of death in almost all patients, and a median overall survival of two to three years.

Patients with metastatic breast

cancer receive treatments that aim to relieve their symptoms and to prolong quality-adjusted life expectancy.

often continues until the cancer starts growing again or until side effects become unacceptable.

If this happens, other drugs might be

The types of drugs used for stage IV (metastatic) breast cancer depend on the hormone receptor status and the HER2 status of the

Women with hormone receptor-positive (estrogen receptor-positive or progesterone receptor-positive) cancers are often treated

first with hormone therapy (tamoxifen or an aromatase inhibitor).

This may be combined with a targeted drug such as a CDK4/6 inhibitor,

everolimus or a PI3K inhibitor.

Women who haven’t yet gone through menopause are often treated with tamoxifen or with medicines

that keep the ovaries from making hormones along with other drugs.

Because hormone therapy can take months to work, chemo is often the

first treatment for patients with serious problems from their cancer spread, such as breathing problems.

Chemotherapy is the main treatment

for women with hormone receptor-negative (ER-negative and PR-negative) cancers.

These breast cancers are either HER2 positive or triple

(Herceptin ® ) may help women with HER2-positive cancers live longer if it’s given along with chemo or with other

medications such as hormonal therapy or other anti-HER2 drugs.

Pertuzumab (Perjeta ® ), another targeted drug, might be

added as well.

Other options might include targeted drugs such as lapatinib (which may be given with certain chemo drugs or hormone therapy)

or ado-trastuzumab emtansine (Kadcyla ® ).

For HER2-negative patients, treatment depends on specific gene mutation status.

Women who have a BRCA mutation

are typically treated with chemotherapy (and hormone therapy, if the cancer is hormone receptor-positive).

An option after getting chemotherapy

is treatment with a PARP inhibitor, such as olaparib or talazoparib.

Women who have a PIK3CA mutation are typically treated with alpelisib,

a targeted PI3K inhibitor that can be used along with fulvestrant to treat postmenopausal women with advanced hormone receptor positive

breast cancer.

For women that have triple-negative

breast cancer (TNBC) — HER2 negative, ER negative, and PR negative — the immunotherapy dug atezolizumab (Tecentriq ® )

if often used, along with albumin-bound paclitaxel (Abraxane ® ) in patients with advanced triple-negative breast cancer

with tumors expressing the PD-L1 protein (which is expressed is about 20% of triple-negative breast cancers.) For women with TNBC and

a BRCA mutation whose cancer no longer responds to common breast cancer chemo drugs, platinum drugs (like cisplatin or carboplatin) may

be considered.

According to the current estimates,

the global therapeutics market for treatment of breast cancer was valued at over $19 billion in 2018 and is expected to reach over $40

billion by the year 2026, at a CAGR of 10.6%.

By way of example, in 2019, worldwide sales for endocrine and targeted therapies treating

ER+ breast cancer patients totaled $9.6 billion.

Given the incidence rate and cost of treatment, by 2027 the market size for adjuvant

therapy, first line treatments and second line treatments could total $25 billion, $8 billion and $4 billion, respectively.

the potential market for treatment of mBC, including treatment of brain metastases (for which there is currently no approved therapy)

is large and growing.

Rationale for Targeting Microtubules in mBC

approved and on market in the U.S.

Women who have a BRCA mutation are typically treated with chemotherapy (and hormone therapy, if the cancer is hormone receptor-positive).

An option after getting chemotherapy is treatment with a PARP inhibitor, such as olaparib or talazoparib.

Women who have a PIK3CA mutation

are typically treated with alpelisib, a targeted PI3K inhibitor that can be used along with fulvestrant to treat postmenopausal women

with advanced hormone receptor positive breast cancer.

women that have triple-negative breast cancer (TNBC) — HER2 negative, ER negative, and PR negative — the immunotherapy dug

atezolizumab (Tecentriq ® ) if often used, along with albumin-bound paclitaxel (Abraxane ® ) in patients with

advanced triple-negative breast cancer with tumors expressing the PD-L1 protein (which is expressed is about 20% of triple-negative breast

cancers.) For women with TNBC and a BRCA mutation whose cancer no longer responds to common breast cancer chemo drugs, platinum drugs

(like cisplatin or carboplatin) may be considered.

to the current estimates, the global therapeutics market for treatment of breast cancer was valued at over $19 billion in 2018 and is

expected to reach over $40 billion by the year 2026, at a CAGR of 10.6%.

By way of example, in 2019, worldwide sales for endocrine and

targeted therapies treating ER+ breast cancer patients totaled $9.6 billion.

Given the incidence rate and cost of treatment, by 2027

the market size for adjuvant therapy, first line treatments and second line treatments could total $25 billion, $8 billion and $4 billion,

respectively.

Accordingly, the potential market for treatment of mBC, including treatment of brain metastases (for which there is currently

no approved therapy) is large and growing.

for Targeting Microtubules in mBC

is approved and on market in the U.S.

as third- or fourth-line treatment of metastatic breast cancer in the following settings:

In combination with capecitabine for the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline and a taxane.

As monotherapy for the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline, a taxane, and capecitabine.

Accordingly, the clinical

benefit of IXEMPRA ® , a microtubule inhibitor, in these patient groups is already established.

We seek to gain approval

of this drug in Europe, for the same mBC patient groups, in connection with our putative IXEMPRA ® -DRP ® companion

diagnostic, used to select and treat the most likely responder patients for the drug, in order to yield a superior therapeutic benefit

in selected patients.

Further, use of our putative DRP ® companion diagnostic is expected to provide an improved benefit

versus risk ratio, which we believe should support an EMA approval.

IXEMPRA ® was previously rejected by the EMA on basis

of the risk versus benefit ratio.

Future Opportunities & Development Plans

for IXEMPRA ®

Potential Development for Neoadjuvant

Since the retrospective validation

of the IXEMPRA ® -DRP ® companion diagnostic showed a 58% increase in complete remission of patients treated

with IXEMPRA ® (see below) as adjuvant therapy, there is a potential to expand the IXEMPRA ® drug plus a DRP ®

companion diagnostic combination to this setting as an attractive alternative to the commonly used paclitaxel.

The neoadjuvant mBC setting

is a substantially larger market opportunity than the third- or fourth-line mBC setting.

DRP ® Companion Diagnostic for

We are developing IXEMPRA ®

together with its retrospectively validated DRP ® companion diagnostic, which we believe enables us to select the patients

most likely to respond to the drug in our clinical trials.

Our Phase 2 clinical trial protocol, including use of the putative IXEMPRA ® -DRP ®

companion diagnostic is in process of being approved by the regulatory agencies in the countries where we are conducting the clinical

trial, and is already approved for use in clinical trials in Belgium, Finland, UK and Poland.

The putative IXEMPRA-DRP ®

companion diagnostic, which comprises 198 expressed genes, was initially retrospectively validated using gene expression data from patient

biopsies in the prior Phase 2 clinical trial of ixabepilone in neoadjuvant breast cancer setting that was conducted by BMS (NCT00455533).

In retrospective analysis of this trial, patients selected with our putative IXEMPRA ® -DRP ® companion diagnostic

was observed to have a 58 percent (58%) increase in complete remission when compared to randomly selected patients treated with ixabepilone.

In sum, we believe our retrospectively

validated putative IXEMPRA ® -DRP ® companion diagnostic accurately and reliably identifies responder patients

to this drug, and we plan to use this DRP ® companion diagnostic for all of our clinical programs to advance IXEMPRA ® ,

including our ongoing Phase 2 clinical trial for mBC.

Existing Microtubule Inhibitors &

Our Opportunity

A number of microtubule inhibitors

are approved and on market for the treatment of multiple cancer types.

These approved drugs include docetaxel (Taxotere ® ),

eribulin (Halaven ® ), ixabepilone (IXEMPRA ® ), paclitaxel (Taxol ® , Abraxane ® ),

and vinorelbine (Navelbine ® ).

Docetaxel, paclitaxel, and albumin-bound paclitaxel are also called taxanes.

Currently marketed

microtubule inhibitors have generated several $billions of sales in the past few years.

For example, sales of Halaven ®

(Eisai) alone were about $400 million in 2019, and sales of vinorelbine exceeded $110 million in 2018.

The following table (2019)

summarizes many of the approved microtubule inhibitors:

Main indications

Hodgkin’s disease, non-Hodgkin lymphoma, histiocytic lymphoma, mycosis fungoides, testis, Kaposi’s sarcoma, choriocarcinoma, breast, kidney

3.7 mg/m 2 – 18.5 mg/m 2

Monotherapy, mechlorethamine, doxorubicin, vincristine, bleomycin, etoposide, dacarbazine, brentuximab, cisplatin, ifosfamide, methotrexate, mitomycine

Leukemias, lymphomas, myeloma, breast, lung, head & neck, sarcomas, Wilms’ tumor, neuroblastoma, retinoblastoma, medulloblastoma,

0.8 mg/m 2 – 2 mg

Monotherapy, doxorubicin, carboplatin mechlorethamine, vinblastine, bleomycin, etoposide, cyclophosphamide, procarbazine, topotecan, dactinomycin, leucovorin, actinomycin D

combination with capecitabine for the treatment of metastatic or locally advanced breast

cancer in patients after failure of an anthracycline and a taxane.

monotherapy for the treatment of metastatic or locally advanced breast cancer in patients

after failure of an anthracycline, a taxane, and capecitabine.

the clinical benefit of IXEMPRA ® , a microtubule inhibitor, in these patient groups is already established.

gain approval of this drug in Europe, for the same mBC patient groups, in connection with our putative IXEMPRA ® -DRP ®

companion diagnostic, used to select and treat the most likely responder patients for the drug, in order to yield a superior therapeutic

benefit in selected patients.

Further, use of our putative DRP ® companion diagnostic is expected to provide an improved

benefit versus risk ratio, which we believe should support an EMA approval.

IXEMPRA ® was previously rejected by the EMA

on basis of the risk versus benefit ratio.

Opportunities & Development Plans for IXEMPRA ®

Development for Neoadjuvant mBC Setting

the retrospective validation of the IXEMPRA ® -DRP ® companion diagnostic showed a 58% increase in complete

remission of patients treated with IXEMPRA ® (see below) as adjuvant therapy, there is a potential to expand the IXEMPRA ®

drug plus a DRP ® companion diagnostic combination to this setting as an attractive alternative to the commonly used

The neoadjuvant mBC setting is a substantially larger market opportunity than the third- or fourth-line mBC setting.

Companion Diagnostic for IXEMPRA ®

are developing IXEMPRA ® together with its retrospectively validated DRP ® companion diagnostic, which we

believe enables us to select the patients most likely to respond to the drug in our clinical trials.

Our Phase 2 clinical trial protocol,

including use of the putative IXEMPRA ® -DRP ® companion diagnostic is in process of being approved by the

regulatory agencies in the countries where we are conducting the clinical trial, and is already approved for use in clinical trials in

Belgium, Finland, UK and Poland.

The putative IXEMPRA-DRP ® companion diagnostic, which comprises 198 expressed genes,

was initially retrospectively validated using gene expression data from patient biopsies in the prior Phase 2 clinical trial of ixabepilone

in neoadjuvant breast cancer setting that was conducted by BMS (NCT00455533).

In retrospective analysis of this trial, patients selected

with our putative IXEMPRA ® -DRP ® companion diagnostic was observed to have a 58% increase in complete remission

when compared to randomly selected patients treated with ixabepilone.

sum, we believe our retrospectively validated putative IXEMPRA ® -DRP ® companion diagnostic accurately and

reliably identifies responder patients to this drug, and we plan to use this DRP ® companion diagnostic for all of our

clinical programs to advance IXEMPRA ® , including our ongoing Phase 2 clinical trial for mBC.

Microtubule Inhibitors & Our Opportunity

number of microtubule inhibitors are approved and on market for the treatment of multiple cancer types.

These approved drugs include

docetaxel (Taxotere ® ), eribulin (Halaven ® ), ixabepilone (IXEMPRA ® ), paclitaxel (Taxol ® ,

Abraxane ® ), and vinorelbine (Navelbine ® ).

Docetaxel, paclitaxel, and albumin-bound paclitaxel are also

called taxanes.

Currently marketed microtubule inhibitors have generated several $billions of sales in the past few years.

sales of Halaven ® (Eisai) alone were about $400 million in 2019, and sales of vinorelbine exceeded $110 million in

The following table (2019) summarizes many of the approved microtubule inhibitors:

Hodgkin’s disease,

non-Hodgkin lymphoma, histiocytic lymphoma, mycosis fungoides, testis, Kaposi’s sarcoma, choriocarcinoma, breast, kidney

– 18.5 mg/m 2

Monotherapy, mechlorethamine,

doxorubicin, vincristine, bleomycin, etoposide, dacarbazine, brentuximab, cisplatin, ifosfamide, methotrexate, mitomycine

Leukemias, lymphomas,

myeloma, breast, lung, head & neck, sarcomas, Wilms’ tumor, neuroblastoma, retinoblastoma, medulloblastoma,

Monotherapy, doxorubicin,

carboplatin mechlorethamine, vinblastine, bleomycin, etoposide, cyclophosphamide, procarbazine, topotecan, dactinomycin, leucovorin,

actinomycin D

ALL, CML, melanoma, breast

3 mg/m 2 – 4 mg/m 2

Monotherapy, cisplatin

NSCLC, Hodgkin’s disease, non-Hodgkin lymphoma, rhabdomyosarcoma, Wilm’s tumor, neuroblastoma

25 mg/m 2 – 30 mg/m 2

NSCLC, Hodgkin’s

disease, non-Hodgkin lymphoma, rhabdomyosarcoma, Wilm’s tumor, neuroblastoma

Monotherapy, cisplatin

Urothelial carcinoma

280 mg/m 2 – 320 mg/m 2

Vincristine Liposomal

Philadelphia chromosome-negative ALL

Ovarian, breast, lung, gastric, Kaposi’s sarcoma

100 mg/m 2 – 210 mg/m 2

Monotherapy, cisplatin, doxorubicin

Breast, lung, prostate, gastric, head & neck

75 mg/m 2 – 100 mg/m 2

Monotherapy, cyclophosphamide, cisplatin, 5-fluorouracil

Philadelphia chromosome-negative

Ovarian, breast, lung,

gastric, Kaposi’s sarcoma

Monotherapy, cisplatin,

Breast, lung, prostate,

gastric, head & neck

Monotherapy, cyclophosphamide,

cisplatin, 5-fluorouracil

Nab-Paclitaxel

Breast, lung, pancreas

100 mg/m 2 – 260 mg/m 2

Monotherapy, carboplatin, gemcitabine

20 mg/m 2 – 25 mg/m 2

Anti-tubulin agents first

approved by FDA (*), EMA (**) or in other countries (***).

Monotherapy, carboplatin,

agents first approved by FDA (*), EMA (**) or in other countries (***).

acute lymphoblastic leukemia;

1 unchanged sentence

non-small-cell lung carcinoma

According to the National

Comprehensive Cancer Network (NCCN) guidelines for treatment of metastatic breast cancer, in the second line metastatic breast cancer

(mBC) setting, for patients who are HER2 negative, ixabepilone in combination with capecitabine is a therapeutic option, along with other

microtubule inhibitors, such as eribulin, cyclophosphamide, docetaxel, and epirubicin.

The choice of a particular microtubule therapeutic

is made by the treating oncologist, and the current lack of suitable companion diagnostics to guide therapy selection has hampered the

introduction of personalized medicine to this patient group.

Our current clinical program for ixabepilone in metastatic breast cancer

is focused on a third-line monotherapy in patients selected with the IXEMPRA ® -DRP ® companion diagnostic.

Despite the success of microtubule

inhibitors as a class in the treatment of cancer, the expanded use of these drugs has been limited by certain toxicities, that include

neutropenia and neurotoxicity, and the development of tumor resistance to the drugs after long-term use.

For example, among taxaIive patients,

primary resistance to taxanes is a critical factor for disease progression.

More than one-third of patients with metastatic breast cancer

do not respond to first-line anthracyclines or taxanes.

to the National Comprehensive Cancer Network (NCCN) guidelines for treatment of metastatic breast cancer, in the second line metastatic

breast cancer (mBC) setting, for patients who are HER2 negative, ixabepilone in combination with capecitabine is a therapeutic option,

along with other microtubule inhibitors, such as eribulin, cyclophosphamide, docetaxel, and epirubicin.

The choice of a particular microtubule

therapeutic is made by the treating oncologist, and the current lack of suitable companion diagnostics to guide therapy selection has

hampered the introduction of personalized medicine to this patient group.

Our current clinical program for ixabepilone in metastatic

breast cancer is focused on a third-line monotherapy in patients selected with the IXEMPRA ® -DRP ® companion

the success of microtubule inhibitors as a class in the treatment of cancer, the expanded use of these drugs has been limited by certain

toxicities, that include neutropenia and neurotoxicity, and the development of tumor resistance to the drugs after long-term use.

example, primary resistance to taxanes is a critical factor for disease progression.

More than one-third of patients with metastatic

breast cancer do not respond to first-line anthracyclines or taxanes.

Taxane resistance rates of up to 55% in anthracycline-pre-treated patients

and up to one-third in anthraIne-naive patients have been reported.

and up to one-third in anthracycline-naive patients have been reported.

Second-line, the same spectrum of outcomes can be expected.

Drug resistance is attributed

to heterogeneity of tumors.

Each patient has his/her own tumor with different characteristics and therefore different therapy outcomes.

The variabilities include but are not limited to different genetic, epigenetic, transcriptomic and proteomic properties.

The genotypic

changes include mutations, gene amplifications, deletions, chromosomal rearrangements, transpositions of the genetic elements, translocations

and microRNA alterations.

Genomic instability generates a great level of intercellular genetic heterogeneity in cancer.

We believe that our microtubule

inhibitor, IXEMPRA ® , together with its DRP ® companion diagnostic, can overcome many of the limitations of

current microtubule inhibitors and has the potential to be a leading drug in its class that can succeed and compete in the marketplace

for the treatment of mBC, and potentially other indications.

The use of the IXEMPRA ® -DRP ® companion diagnostic

to select and treat only those mBC patients most likely to respond to the drug (while excluding treatment of likely non-responders) can

mitigate toxicity events in non-responder patients, while increasing therapeutic benefit in the identified responder patient population.

The success of our IXEMPRA ® program will establish the ability of our DRP ® platform to expand oncology markets

for approved cancer therapeutics through a personalized medicine approach using DRP ® companion diagnostics.

Secondary Therapeutic Programs

Overview of our DRP ® companion

diagnostic for LiPlaCis ® (targeted, liposomal cisplatin)

Mechanisms of Action

Cisplatin (or cisplatinum

or cis -diamminedichloroplatinum (II)) is a chemotherapeutic drug that has been used, since the 1970s, in the treatment of various

types of human cancers such as ovarian, lung, head and neck, testicular and bladder.

Cisplatin has demonstrated anti-cancer activity against

various types of cancers such as germ cell tumors, sarcomas, carcinomas as well as lymphomas.

The mechanism of action of cisplatin has

been associated with ability to crosslink with the urine bases on the DNA to form DNA adducts, preventing repair of the DNA leading to

DNA damage and subsequently induces apoptosis (programmed cell death) within cancer cells.

However, the drug exhibits certain level

of resistance including increased repair of the damaged DNA, reduction in the accumulation of the drug intracellular and cytosolic inactivation

of cisplatin.

The drug is also characterized

by various toxic side effects including nausea, nephrotoxicity, cardiotoxicity, hepatotoxicity and neurotoxicity.

Due to various side

effects as well as drug resistance, other anti-cancer drugs that contain platinum such as carboplatin and oxaliplatin, among others, have

been used in combination with cisplatin in chemotherapeutic treatment of cancer.

In addition to the cytotoxic effects, cisplatin has immunosuppressive

and radio-sensitizing properties.

As used in this section of this report describing our therapeutic candidate LiPlaCis ® ,

statements regarding the use of our proprietary DRP ® companion diagnostics or our proprietary DRP ® platform

or our observations that our therapeutic candidate LiPlaCis ® may have anti-cancer or anti-tumor activity or is observed

to be well tolerated in a patient population should not be construed to mean that we have resolved all issues of safety and/or efficacy

for our therapeutic candidate LiPlaCis ® or our putative Cisplatin-DRP ® companion diagnostic.

Issues of safety

and efficacy for any therapeutic candidate or companion diagnostic may only be determined by the U.S.

FDA or other applicable regulatory

authorities in jurisdictions outside the United States.

LiPlaCis ® is

a novel, targeted liposomal formulation of the anti-cancer drug cisplatin.

Liposomes are closed spherical vesicles, having an interior

aqueous space entrapped by a bilayer lipid membrane.

LiPlaCis ® liposomes have cisplatin encapsulated in the interior aqueous

space of the liposomes and the bilayer membrane is constituted by 3 phospholipids.

The use of liposomes as drug carriers has been

limited due to the rapid clearance of these carriers from the blood stream by the reticuloendothelial system.

The addition of polyethylenglycol

(PEG) polymers to the surface of the liposomes leads to reduced clearance rates.

As a result, the use of liposomes is now recognized as

a promising strategy for tumor-targeted drug delivery.

Due to the leaky tumor vasculature and the incomplete lymphatic drainage system

of tumors, long circulatory liposomes may be preferentially trapped and therefore accumulate in cancer tissues.

The preferential entrapment

and accumulation of the liposomes in the cancer tissue is also known as the enhanced permeability and retention effect (EPR-effect).

of the trapping of liposomes, significantly more drug substance is present at the site of the tumor compared to administration of plain

drug products.

However, it has also been

realized that the degradation of liposomes and release of the encapsulated drug(s) after the liposomes accumulate in the tumor are critical

elements to the success of liposomal drug delivery.

This is the case for hydrophilic drugs such as cisplatin, which do not readily diffuse

across the liposomal membrane.

Such hydrophilic drugs require that tumor-specific degradation of the liposomal carrier takes place before

the drug can be released and exert its cytotoxic action on the cancer cells.

In fact, the absence of a trigger mechanism in the tumor

tissue was proposed as the explanation for the lack of anti-tumor activity in clinical trials using cisplatin containing Stealth ®

liposomes (SPI-077) (PEGylated liposomes).

In these studies, a high level of cisplatin was found in the tumor tissue inside the liposomes,

but it was not bioavailable.

LiPlaCis ® includes

a tumor-specific targeting mechanism on the surface of its liposomes, which triggers the release of cisplatin specifically in tumor tissue.

Secretory sPLA2 is a small secreted and phospholipid-degrading enzyme, which is overexpressed in cancer tissue compared to normal tissue.

Until now, 10 catalytically active isoforms of sPLA2 have been identified, of which the Group II sPLA2 isoform seems to be the most predominant

form in cancer.

In normal tissue, Group II sPLA2 has been found to be expressed in cartilage, digestive tract (stomach, duodenum, jejunum,

ileum and colon), and in prostate-, parotid- and lacrimal glands.

This enzyme breaks down the LiPlaCis ® once it accumulates

in the cancer tissue due to the EPR-effect.

The lipid composition of the LiPlaCis ® is designed to be specifically susceptible

to degradation by sPLA2.

This leads to tumor-specific release of the encapsulated drug substance in the target tissue.

sPLA2 has shown

to be overexpressed in a wide range of tumors such as stomach, breast, gastric, liver, lung and pancreatic cancers.

It has been shown

that sPLA2 expression is increased with advancing stage of cancer disease and that enhanced expression of sPLA2 may be related to tumor

LiPlaCis ® enables

the targeted transport of high concentrations of encapsulated anti-cancer drugs to cancer tissue.

After IV administration, LiPlaCis ®

will naturally extravasate and accumulate in the extracellular space of the tumor tissue.

The secretion of sPLA2 into the extracellular

space of the cancer tissue provides further support to the overall concept of achieving a tumor-specific degradation of the LiPlaCis ®

after extravasation.

The targeted delivery of cisplatin to tumors that is achieved by LiPlaCis ® has the benefits of transporting

this mutagenic and toxic chemotherapeutic to cancer cells while avoiding exposure to healthy cells.

The tumor-specific degradation of

the liposomal drug carriers by overexpressed sPLA2 offers a novel way to achieve a targeted and triggered release of the encapsulated

drugs in the cancer tissue without any prior knowledge of the position and size of the tumor, e.g.

undetected metastases.

DRP ® Companion Diagnostic for

LiPlaCis ® is

being clinically developed by Chosa ApS together with our prospectively validated DRP ® companion diagnostic for cisplatin,

which enables Chosa to select the patients most likely to respond to the drug in their clinical trials.

In August 2019, the FDA approved

our IDE application for use of our Cisplatin-DRP ® companion diagnostic in a planned pivotal Phase 3 clinical trial

of LiPlaCis ® in mBC.

In June 2019, we announced that the FDA had provided feedback on our pending IND application

and proposed pivotal Phase 3 clinical trial in mBC using the Cisplatin-DRP ® .

The Cisplatin-DRP ® , which comprises

205 expressed genes, was initially developed using gene expression data from the National Cancer Institute NCI60 panel of cancer cell

We have out-licensed our putative Cisplatin-DRP ® companion diagnostic to Chosa as described above.

Our putative Cisplatin-DRP ® companion

diagnostic was retrospectively validated in two non-small cell lung cancer (NSCLC) cohorts.

Molecular prediction of adjuvant cisplatin

anti-cancer activity in NSCLC showed a significant prediction at 3-year survival from surgery in univariate (HR = 0.138 (95% CI:0.035

– 0.537), p = 0.004) and multivariate analysis (HR = 0.14 (95% CI:0.030 – 0.6), p = 0.0081).

In sum, we believe our retrospectively

and prospectively validated putative LiPlaCis ® -DRP ® companion diagnostic accurately and reliably identifies

responder patients to LiPlaCis ® , and we plan to use this DRP ® companion diagnostic for all of our clinical

programs to advance LiPlaCis ® , including the planned, expanded Phase 2 clinical trial for mBC being advanced by our licensee,

Overview of 2X-111 (targeted, liposomal

Mechanisms of Action

2X-111 is an advanced, targeted

liposomal formulation of doxorubicin, one of the world’s most widely used chemotherapies.

The specific 2X-111 formulation, which

exploits a unique, glutathione enhanced PEG-liposomal delivery system, allows the drug to cross the blood-brain barrier (BBB), thereby

enabling the treatment of primary brain tumors, such as glioblastoma multiforme (GBM), and secondary brain tumors that originated from

cancers outside the brain, such as metastatic breast cancer.

Doxorubicin is a type of chemotherapy

drug called an anthracycline.

It slows or stops the growth of cancer cells by blocking an enzyme called topo isomerase 2, which is necessary

for DNA replication.

Topo isomerase 2 is an enzyme that cuts both strands of the DNA helix simultaneously in order to manage DNA tangles

and supercoils.

Cancer cells need this enzyme to divide and grow.

Doxorubicin is approved and in use for a number of cancer types, including

breast cancer, bladder cancer, Kaposi’s sarcoma, lymphoma, and acute lymphocytic leukemia.

It is often used together with other

chemotherapy agents.

Liposomes are closed spherical

vesicles, having an interior aqueous space entrapped by a bilayer lipid membrane.

2X-111 liposomes have doxorubicin encapsulated in the

interior aqueous space of the liposomes and the bilayer membrane is constituted by 3 phospholipids.

resistance is attributed to heterogeneity of tumors.

Each patient has his/her own tumor with different characteristics and therefore

different therapy outcomes.

The variabilities include but are not limited to different genetic, epigenetic, transcriptomic and proteomic

The genotypic changes include mutations, gene amplifications, deletions, chromosomal rearrangements, transpositions of the

genetic elements, translocations and microRNA alterations.

Genomic instability generates a great level of intercellular genetic heterogeneity

believe that our microtubule inhibitor, IXEMPRA ® , together with its DRP ® companion diagnostic, can overcome

many of the limitations of current microtubule inhibitors and has the potential to be a leading drug in its class that can succeed and

compete in the marketplace for the treatment of mBC, and potentially other indications.

The use of the IXEMPRA ® -DRP ®

companion diagnostic to select and treat only those mBC patients most likely to respond to the drug (while excluding treatment

of likely non-responders) can mitigate toxicity events in non-responder patients, while increasing therapeutic benefit in the identified

responder patient population.

The success of our IXEMPRA ® program will establish the ability of our DRP ®

platform to expand oncology markets for approved cancer therapeutics through a personalized medicine approach using DRP ®

companion diagnostics.

or Partnered Programs

following programs have been outlicensed or are part of business development deals and do not require the heavy resource commitment from

The development of these assets is largely the responsibility of the partner with limited support from Allarity to enable the

DRP ® companion diagnostic for each asset.

The new leadership instituted in December 2023 is currently evaluating each

of these programs.

These remain in the 10K for reference as critical decisions about these programs have not yet been finalized.

of our DRP ® companion diagnostic for LiPlaCis ® (targeted, liposomal cisplatin)

(or cisplatinum or cis -diamminedichloroplatinum (II)) is a chemotherapeutic drug that has been used, since the 1970s, in the treatment

of various types of human cancers such as ovarian, lung, head and neck, testicular and bladder.

Cisplatin has demonstrated anti-cancer

activity against various types of cancers such as germ cell tumors, sarcomas, carcinomas as well as lymphomas.

The mechanism of action

of cisplatin has been associated with ability to crosslink with the urine bases on the DNA to form DNA adducts, preventing repair of

the DNA leading to DNA damage and subsequently induces apoptosis (programmed cell death) within cancer cells.

However, the drug

exhibits certain level of resistance including increased repair of the damaged DNA, reduction in the accumulation of the drug intracellular

and cytosolic inactivation of cisplatin.

drug is also characterized by various toxic side effects including nausea, nephrotoxicity, cardiotoxicity, hepatotoxicity and neurotoxicity.

Due to various side effects as well as drug resistance, other anti-cancer drugs that contain platinum such as carboplatin and oxaliplatin,

among others, have been used in combination with cisplatin in chemotherapeutic treatment of cancer.

In addition to the cytotoxic effects,

cisplatin has immunosuppressive and radio-sensitizing properties.

As used in this section of this report describing our therapeutic candidate

LiPlaCis ® , statements regarding the use of our proprietary DRP ® companion diagnostics or our proprietary

DRP ® platform or our observations that our therapeutic candidate LiPlaCis ® may have anti-cancer or anti-tumor

activity or is observed to be well tolerated in a patient population should not be construed to mean that we have resolved all issues

of safety and/or efficacy for our therapeutic candidate LiPlaCis ® or our putative Cisplatin-DRP ® companion

Issues of safety and efficacy for any therapeutic candidate or companion diagnostic may only be determined by the U.S.

or other applicable regulatory authorities in jurisdictions outside the United States.

is a novel, targeted liposomal formulation of the anti-cancer drug cisplatin.

Liposomes are closed spherical vesicles, having an

interior aqueous space entrapped by a bilayer lipid membrane.

LiPlaCis ® liposomes have cisplatin encapsulated in the interior

aqueous space of the liposomes and the bilayer membrane is constituted by 3 phospholipids.

The use of liposomes as drug carriers

2 unchanged sentences

polyethylenglycol (PEG) polymers to the surface of the liposomes leads to reduced clearance rates.

As a result, the use of liposomes is

now recognized as a promising strategy for tumor-targeted drug delivery.

As a result, the use of liposomes

is now recognized as a promising strategy for tumor-targeted drug delivery.

Due to the leaky tumor vasculature and the incomplete lymphatic

1 unchanged sentence

The preferential

entrapment and accumulation of the liposomes in the cIncer tissue is also known as the enhanced permeability and retention effect (EPR-effect).

As a consequence of the trapping of liposomes, significantly more drug substance is present at the site of the tumor compared to administration

entrapment and accumulation of the liposomes in the cancer tissue is also known as the enhanced permeability and retention effect (EPR-effect).

Because of the trapping of liposomes, significantly more drug substance is present at the site of the tumor compared to administration

of plain drug products.

Most PEG-liposomal cancer

drugs cannot pass the BBB and therefore cannot be used for treatment of primary or secondary brain tumors.

The delicate metabolic homeostasis

of the central nervous system is largely maintained by the BBB, which plays a key role in excluding potentially neurotoxic and exogenous

compounds from the brain, while still allowing the penetration and uptake of essential nutrients.

Many potentially highly efficacious

anticancer drugs are currently not available to treat brain tumors because they do not adequately cross the BBB, and therefore do not

reach the brain.

Glutathione is an endogenous

tri-peptide with antioxidant-like properties in the brain and its active (sodium-dependent) transport receptor is highly expressed on

The unique 2X-111 glutathione-modified PEG-liposome enables transport of encapsulated drugs, such as doxorubicin past the BBB,

enhancing the delivery of such drugs to the brain.

As used in this section of this report describing our therapeutic candidate 2X-111,

statements regarding the use of our proprietary DRP ® companion diagnostics or our proprietary DRP ® platform

it has also been realized that the degradation of liposomes and release of the encapsulated drug(s) after the liposomes accumulate in

the tumor are critical elements to the success of liposomal drug delivery.

This is the case for hydrophilic drugs such as cisplatin,

which do not readily diffuse across the liposomal membrane.

Such hydrophilic drugs require that tumor-specific degradation of the liposomal

carrier takes place before the drug can be released and exert its cytotoxic action on the cancer cells.

In fact, the absence of a trigger

mechanism in the tumor tissue was proposed as the explanation for the lack of anti-tumor activity in clinical trials using cisplatin

containing Stealth ® liposomes (SPI-077) (PEGylated liposomes).

In these studies, a high level of cisplatin was found in

the tumor tissue inside the liposomes, but it was not bioavailable.

includes a tumor-specific targeting mechanism on the surface of its liposomes, which triggers the release of cisplatin specifically

in tumor tissue.

Secretory sPLA2 is a small secreted and phospholipid-degrading enzyme, which is overexpressed in cancer tissue compared

to normal tissue.

Until now, 10 catalytically active isoforms of sPLA2 have been identified, of which the Group II sPLA2 isoform seems

to be the most predominant form in cancer.

In normal tissue, Group II sPLA2 has been found to be expressed in cartilage, digestive tract

(stomach, duodenum, jejunum, ileum and colon), and in prostate-, parotid- and lacrimal glands.

This enzyme breaks down the LiPlaCis ®

once it accumulates in the cancer tissue due to the EPR-effect.

The lipid composition of the LiPlaCis ® is designed

to be specifically susceptible to degradation by sPLA2.

This leads to tumor-specific release of the encapsulated drug substance in the

target tissue.

sPLA2 has shown to be overexpressed in a wide range of tumors such as stomach, breast, gastric, liver, lung and pancreatic

It has been shown that sPLA2 expression is increased with advancing stage of cancer disease and that enhanced expression of

sPLA2 may be related to tumor progression.

enables the targeted transport of high concentrations of encapsulated anti-cancer drugs to cancer tissue.

After IV administration,

LiPlaCis ® will naturally extravasate and accumulate in the extracellular space of the tumor tissue.

The secretion of sPLA2

into the extracellular space of the cancer tissue provides further support to the overall concept of achieving a tumor-specific degradation

of the LiPlaCis ® after extravasation.

The targeted delivery of cisplatin to tumors that is achieved by LiPlaCis ®

has the benefits of transporting this mutagenic and toxic chemotherapeutic to cancer cells while avoiding exposure to healthy cells.

The tumor-specific degradation of the liposomal drug carriers by overexpressed sPLA2 offers a novel way to achieve a targeted and triggered

release of the encapsulated drugs in the cancer tissue without any prior knowledge of the position and size of the tumor, e.g.

Companion Diagnostic for LiPlaCis ®

is being clinically developed by Chosa ApS together with our prospectively validated DRP ® companion diagnostic for

cisplatin, which enables Chosa to select the patients most likely to respond to the drug in their clinical trials.

In August 2019,

the FDA approved our IDE application for use of our Cisplatin-DRP ® companion diagnostic in a planned pivotal Phase

3 clinical trial of LiPlaCis ® in mBC.

In June 2019, we announced that the FDA had provided feedback on our

pending IND application and proposed pivotal Phase 3 clinical trial in mBC using the Cisplatin-DRP ® .

The Cisplatin-DRP ® ,

which comprises 205 expressed genes, was initially developed using gene expression data from the National Cancer Institute NCI60 panel

of cancer cell lines.

We have out-licensed our putative Cisplatin-DRP ® companion diagnostic to Chosa as described above.

putative Cisplatin-DRP ® companion diagnostic was retrospectively validated in two non-small cell lung cancer (NSCLC) cohorts.

Molecular prediction of adjuvant cisplatin anti-cancer activity in NSCLC showed a significant prediction at 3-year survival from

surgery in univariate (HR = 0.138 (95% CI:0.035 – 0.537), p = 0.004) and multivariate analysis (HR = 0.14 (95% CI:0.030

– 0.6), p = 0.0081).

sum, we believe our retrospectively and prospectively validated putative LiPlaCis ® -DRP ® companion diagnostic

accurately and reliably identifies responder patients to LiPlaCis ® , and we plan to use this DRP ® companion

diagnostic for all of our clinical programs to advance LiPlaCis ® , including the planned, expanded Phase 2 clinical trial

for mBC being advanced by our licensee, Chosa ApS.

of 2X-111 (targeted, liposomal doxorubicin)

is an advanced, targeted liposomal formulation of doxorubicin, one of the world’s most widely used chemotherapies.

2X-111 formulation, which exploits a unique, glutathione enhanced PEG-liposomal delivery system, allows the drug to cross the BBB, thereby

enabling the treatment of primary brain tumors, such as GBM, and secondary brain tumors that originated from cancers outside the brain,

such as metastatic breast cancer.

is a type of chemotherapy drug called an anthracycline.

It slows or stops the growth of cancer cells by blocking an enzyme called topo

isomerase 2, which is necessary for DNA replication.

Topo isomerase 2 is an enzyme that cuts both strands of the DNA helix simultaneously

in order to manage DNA tangles and supercoils.

Cancer cells need this enzyme to divide and grow.

Doxorubicin is approved and in use for

a number of cancer types, including breast cancer, bladder cancer, Kaposi’s sarcoma, lymphoma, and acute lymphocytic leukemia.

It is often used together with other chemotherapy agents.

are closed spherical vesicles, having an interior aqueous space entrapped by a bilayer lipid membrane.

2X-111 liposomes have doxorubicin

encapsulated in the interior aqueous space of the liposomes and the bilayer membrane is constituted by 3 phospholipids.

The use of liposomes

as drug carriers has been limited due to the rapid clearance of these carriers from the blood stream by the reticuloendothelial system.

The addition of polyethylenglycol (PEG) polymers to the surface of the liposomes leads to reduced clearance rates.

As a result, the use

of liposomes is now recognized as a promising strategy for tumor-targeted drug delivery.

Due to the leaky tumor vasculature and the incomplete

lymphatic drainage system of tumors, long circulatory liposomes may be preferentially trapped and therefore accumulate in cancer tissues.

The preferential entrapment and accumulation of the liposomes in the cIncer tissue is also known as the enhanced permeability and retention

effect (EPR-effect).

As a consequence of the trapping of liposomes, significantly more drug substance is present at the site of the tumor

compared to administration of plain drug products.

PEG-liposomal cancer drugs cannot pass the BBB and therefore cannot be used for treatment of primary or secondary brain tumors.

metabolic homeostasis of the central nervous system is largely maintained by the BBB, which plays a key role in excluding potentially

neurotoxic and exogenous compounds from the brain, while still allowing the penetration and uptake of essential nutrients.

Many potentially

highly efficacious anticancer drugs are currently not available to treat brain tumors because they do not adequately cross the BBB, and

therefore do not reach the brain.

is an endogenous tri-peptide with antioxidant-like properties in the brain and its active (sodium-dependent) transport receptor is highly

expressed on the BBB.

The unique 2X-111 glutathione-modified PEG-liposome enables transport of encapsulated drugs, such as doxorubicin

past the BBB, enhancing the delivery of such drugs to the brain.

As used in this section of this report describing our therapeutic candidate

2X-111, statements regarding the use of our proprietary DRP ® companion diagnostics or our proprietary DRP ® platform

or our observations that our therapeutic candidate 2X-111 may have anti-cancer or anti-tumor activity or is observed to be well tolerated

1 unchanged sentence

candidate 2X-111 ® or our putative Doxorubicin-DRP ® companion diagnostic.

Issues of safety and efficacy for

any therapeutic candidate or companion diagnostic may only be determined by the U.S.

FDA or other applicable regulatory authorities in

jurisdictions outside the United States.

Pre-Clinical Studies

Preclinical studies have been

performed in order to determine the anti-cancer activity and toleration of 2X-111 both systemically and in the CNS prior to the start

of the human clinical trials.

2X-111 showed significantly better tumor growth inhibition and survival benefit in rodents with brain tumors

as compared to normal PEGylated liposomal doxorubicin (Caelyx ® /Doxil ® ).

In a systemic breast cancer animal

model, the tumor suppression was equal between 2X-111 and Caelyx ® /Doxil ® .

Moreover, compared to Caelyx ® /Doxil ® ,

enhanced doxorubicin delivery by 2X-111 across the BBB was observed, with a favorable pharmacokinetic and safety profile in animal models.

Issues of safety and efficacy

for any therapeutic candidate or companion diagnostic may only be determined by the U.S.

FDA or other applicable regulatory authorities

in jurisdictions outside the United States.

studies have been performed in order to determine the anti-cancer activity and toleration of 2X-111 both systemically and in the CNS

prior to the start of the human clinical trials.

2X-111 showed significantly better tumor growth inhibition and survival benefit in rodents

with brain tumors as compared to normal PEGylated liposomal doxorubicin (Caelyx ® /Doxil ® ).

In a systemic

breast cancer animal model, the tumor suppression was equal between 2X-111 and Caelyx ® /Doxil ® .

compared to Caelyx ® /Doxil ® , enhanced doxorubicin delivery by 2X-111 across the BBB was observed, with a

favorable pharmacokinetic and safety profile in animal models.

The following graphs represent some of the preclinical observations:

Prior Clinical Trials

2X-111 (formerly 2B3-101)

was previously evaluated in Phase I/IIa, multi-center, open-label, dose-escalation clinical trial sponsored by 2-BBB Medicines, B.V.

Clinical Trials

(formerly 2B3-101) was previously evaluated in Phase I/IIa, multi-center, open-label, dose-escalation clinical trial sponsored by 2-BBB

Medicines, B.V.

(NCT01818713;

NCT01386580).

Dieta Brandsma, MD, PhD, Division of Neuro-Oncology, Netherlands Cancer Institute in Amsterdam was the Coordinating Investigator.

Dieta Brandsma, MD, PhD, Division of Neuro-Oncology, Netherlands Cancer Institute in Amsterdam

was the Coordinating Investigator.

There were numerous trial sites in the Netherlands, Belgium, and France.

The purpose of this study

was the determination of safety, tolerability, and PK of 2X-111 both as single agent and in combination with trastuzumab.

the study aimed to explore the preliminary anti-tumor activity of 2X-111 as single agent in patients with solid tumors and brain metastases

or recurrent malignant glioma, as well as in patients with various forms of breast cancer in combination with trastuzumab in Her2+ breast

cancer patients with brain metastases.

purpose of this study was the determination of safety, tolerability, and PK of 2X-111 both as single agent and in combination with trastuzumab.

Furthermore, the study aimed to explore the preliminary anti-tumor activity of 2X-111 as single agent in patients with solid tumors and

brain metastases or recurrent malignant glioma, as well as in patients with various forms of breast cancer in combination with trastuzumab

in Her2+ breast cancer patients with brain metastases.

The study was performed in two phases:

a dose escalation phase following a standard

design to determine dose-limiting toxicities (DLT) and a safe dose (MTD) of 2X-111, followed by four expanded study arms where patients

were treated at the MTD to confirm the Recommended Phase II Dose (RP2D).

84 patients were enrolled

in this study, including 37 in the dose escalation phase and an additional 47 patients in the expansion safety cohorts.

Only patients

who meet all the inclusion and exclusion criteria were enrolled.

Two populations were used to analyze the study data including:

Safety (SAF):

“3+3” design to determine dose-limiting toxicities (DLT) and a safe dose (MTD) of 2X-111, followed by four expanded study

arms where patients were treated at the MTD to confirm the Recommended Phase II Dose (RP2D).

patients were enrolled in this study, including 37 in the dose escalation phase and an additional 47 patients in the expansion safety

Only patients who meet all the inclusion and exclusion criteria were enrolled.

Two populations were used to analyze the study

data including:

Patients who received at least one dose of 2X-111 were evaluable for safety analysis.

Intention to Treat (ITT):

All patients in the SAF who have received at least one dose of trial medication were evaluable for ITT analysis.

To be eligible to participate

in this study, candidates must have met the following eligibility criteria:

Patients with pathologically confirmed diagnosis of advanced, recurrent solid tumors and unequivocal evidence of brain metastases that were refractory to standard therapy or for whom no standard therapy existed or with unequivocal evidence of newly diagnosed un- treated brain metastases and controlled extra cranial disease, which per the multi-disciplinary team decision did not require immediate radiotherapy, surgery, or standard systemic chemotherapy.

Brain metastases may have been stable, progressive, symptomatic or asymptomatic brain metastasis/es.

Stable or decreasing doses of steroids (e.g.

dexamethasone) for a minimum of 7 days prior to baseline MRI or non-enzyme inducing antiepileptic drugs were allowed.

Patients with pathology confirmed diagnosis of advanced, recurrent primary malignant (grade III and IV) glioma that were refractory to standard therapy or for whom no standard therapy existed.

to Treat (ITT):

All patients in the Safety Population who have received at least one dose

of trial medication were evaluable for ITT analysis.

be eligible to participate in this study, candidates must have met the following eligibility criteria:

with pathologically confirmed diagnosis of advanced, recurrent solid tumors and unequivocal

evidence of brain metastases that were refractory to standard therapy or for whom no standard

therapy existed or with unequivocal evidence of newly diagnosed un- treated brain metastases

and controlled extra cranial disease, which per the multi-disciplinary team decision did

not require immediate radiotherapy, surgery, or standard systemic chemotherapy.

Brain metastases

may have been stable, progressive, symptomatic or asymptomatic brain metastasis/es.

or decreasing doses of steroids (e.g.

dexamethasone) for a minimum of 7 days prior to

baseline MRI or non-enzyme inducing antiepileptic drugs were allowed.

with pathology confirmed diagnosis of advanced, recurrent primary malignant (grade III and

IV) glioma that were refractory to standard therapy or for whom no standard therapy existed.

Stable or decreasing doses of steroids (e.g.

dexamethasone) for a minimum of 7 days prior to baseline MRI or non-enzyme inducing antiepileptic drugs were allowed.

2X-111 in combination with

trastuzumab dose-escalation phase:

Patients with histologically-confirmed Her2+ (IHC 3+ or fluorescence in situ hybridization [FISH] amplified;

by clinical assay on either primary or metastatic tumor) adenocarcinoma of the breast with unequivocal evidence of brain metastases that were refractory to standard therapy or for whom no standard therapy exist or with unequivocal evidence of newly diagnosed untreated brain metastases and controlled extra cranial disease, which per the multi-disciplinary team decision did not require immediate radiotherapy, surgery, or standard systemic chemotherapy could be included to this escalation phase as well.

Breast cancer brain metastases

study arm of the expansion phase:

Patients with pathologically confirmed diagnosis of advanced, recurrent breast cancer with at least one progressive and/or new metastatic brain lesion, that were refractory to standard therapy or for whom no standard therapy exists.

dexamethasone) for a minimum of 7 days

prior to baseline MRI or non-enzyme inducing antiepileptic drugs were allowed.

in combination with trastuzumab dose-escalation phase:

with histologically-confirmed Her2+ (IHC 3+ or fluorescence in situ hybridization [FISH]

by clinical assay on either primary or metastatic tumor) adenocarcinoma of the

breast with unequivocal evidence of brain metastases that were refractory to standard therapy

or for whom no standard therapy exist or with unequivocal evidence of newly diagnosed untreated

brain metastases and controlled extra cranial disease, which per the multi-disciplinary team

decision did not require immediate radiotherapy, surgery, or standard systemic chemotherapy

could be included to this escalation phase as well.

cancer brain metastases study arm of the expansion phase:

with pathologically confirmed diagnosis of advanced, recurrent breast cancer with at least

one progressive and/or new metastatic brain lesion, that were refractory to standard therapy

or for whom no standard therapy exists.

Stable or decreasing dosages of steroids (e.g.

dexamethasone) for 7 days prior to baseline MRI and/or non-enzyme inducing antiepileptic drugs were allowed.

Patients with pathologically confirmed diagnosis of advanced breast cancer with newly diagnosed, untreated, brain metastases and controlled extracranial disease, which per the multi-disciplinary team decision do not require immediate radiotherapy, surgery, or standard systemic chemotherapy.

Once the MTD of 2B3-101 with trastuzumab has been determined, patients with histologically-confirmed Her2+ (IHC 3+ or fluorescence in situ hybridization [FISH] amplified;

by clinical assay on either primary or metastatic tumor) adenocarcinoma of the breast with at least one progressive and/or new metastatic brain lesion, that were refractory to standard therapy or for which no standard therapy exist or with unequivocal evidence of newly diagnosed untreated brain metastases and controlled extra cranial disease, which per the multi-disciplinary team decision do not require immediate radiotherapy, surgery, or standard systemic chemotherapy, could be included to this expansion phase as well.

SCLC brain metastases study

arm of the expansion phase:

Patients with pathologically confirmed diagnosis of advanced, recurrent SCLC with at least one progressive and/or new metastatic brain lesion, that were refractory to standard therapy or for whom no standard therapy exists.

dexamethasone)

for 7 days prior to baseline MRI and/or non-enzyme inducing antiepileptic drugs were

with pathologically confirmed diagnosis of advanced breast cancer with newly diagnosed, untreated,

brain metastases and controlled extracranial disease, which per the multi-disciplinary team

decision do not require immediate radiotherapy, surgery, or standard systemic chemotherapy.

the MTD of 2B3-101 with trastuzumab has been determined, patients with histologically-confirmed

Her2+ (IHC 3+ or fluorescence in situ hybridization [FISH] amplified;

by clinical assay on

either primary or metastatic tumor) adenocarcinoma of the breast with at least one progressive

and/or new metastatic brain lesion, that were refractory to standard therapy or for which

no standard therapy exist or with unequivocal evidence of newly diagnosed untreated brain

metastases and controlled extra cranial disease, which per the multi-disciplinary team decision

do not require immediate radiotherapy, surgery, or standard systemic chemotherapy, could

be included to this expansion phase as well.

brain metastases study arm of the expansion phase:

with pathologically confirmed diagnosis of advanced, recurrent SCLC with at least one progressive

and/or new metastatic brain lesion, that were refractory to standard therapy or for whom

no standard therapy exists.

Stable or decreasing dosages of steroids (e.g.

dexmethasone) for 7 days prior to baseline MRI and/or use of non-enzyme inducing antiepileptic drugs were allowed.

Patients with pathologically confirmed diagnosis of advanced SCLC with newly diagnosed, untreated, brain metastases and controlled extra cranial disease, which per the multi-disciplinary team decision do not require immediate radiotherapy, surgery, or standard systemic chemotherapy.

Melanoma brain metastases

study arm of the expansion phase:

Patients with pathologically confirmed diagnosis of advanced, recurrent melanoma with at least one progressive and/or new metastatic brain lesion, that were refractory to standard therapy or for whom no standard therapy exists.

dexmethasone)

for 7 days prior to baseline MRI and/or use of non-enzyme inducing antiepileptic drugs

were allowed.

with pathologically confirmed diagnosis of advanced SCLC with newly diagnosed, untreated,

brain metastases and controlled extra cranial disease, which per the multi-disciplinary team

decision do not require immediate radiotherapy, surgery, or standard systemic chemotherapy.

brain metastases study arm of the expansion phase:

with pathologically confirmed diagnosis of advanced, recurrent melanoma with at least one

progressive and/or new metastatic brain lesion, that were refractory to standard therapy

or for whom no standard therapy exists.

Stable or decreasing dosages of steroids (e.g.

dexamethasone) for 7 days prior to baseline MRI and/or use of non-enzyme inducing antiepileptic drugs were allowed.

Patients with pathologically confirmed diagnosis of advanced melanoma with newly diagnosed, untreated, brain metastases and controlled extra cranial disease, which per the multi-disciplinary team decision do not require immediate radiotherapy, surgery, or standard systemic chemotherapy.

Recurrent malignant glioma

study arm of the expansion phase:

Patients with histologically proven glioma grade IV, which were progressive following first line treatment with surgery or biopsy followed by fractionated radiotherapy with concurrent temozolomide as chemotherapy.

Patients with recurrent histologically confirmed malignant (WHO grade III and IV) glioma or histologically confirmed low-grade (WHO grade II) glioma with radiographic evidence of malignant transformation by MRI, that were refractory to standard therapy, or for whom no standard therapy exists or did not require immediate standard therapy per the multi- disciplinary team decision.

Patients in both groups should have stable and decreasing dosage of steroids (e.g.

dexamethasone) for a minimum of 7 days prior to baseline MRI.

Non-enzyme inducing antiepileptic drugs are allowed.

In the single agent dose-escalation

phase, patients eligible for the study were assigned to a dose level cohort.

The starting dose was 5 mg/m 2 , which was equal

to 1/10 of the human equivalent dose of the LD10 of 2X-111 in rats.

Dose levels for subsequent cohorts were 10, 20, 30 mg/m 2

and steps of 10 mg/m 2 thereafter.

Patients received a single IV dose of 2X-111 on day 1 of each cycle.

To minimize the risk

of infusion reactions 5% of the total dose of 2B3-101 (in mg) was infused slowly over the first 30 minutes.

If tolerated, the infusion

was completed over the next hour for a total infusion time of 90 minutes.

Each treatment cycle consisted of 21 days.

In the combination with trastuzumab

dose-escalation phase, patients were assigned to a 2X-111 dose level cohort.

The starting dose of 2X-111 was 40 mg/m 2 every

This dose has been selected based upon safety information from patients treated with 2X-111 at this dose level, as well as upon

previous treatment with PEGylated liposomal doxorubicin in combinations trastuzumab.

In both cases, dose-escalation

was conducted in steps of 10 mg/m 2 up to the MTD level determined for 2X-111 as single agent.

The trastuzumab dose remained

fixed to a loading dose of 8 mg/kg at day 1 and 6 mg/kg every 3 weeks at the subsequent cycles throughout the determination of the MTD.

dexamethasone)

for 7 days prior to baseline MRI and/or use of non-enzyme inducing antiepileptic drugs

were allowed.

with pathologically confirmed diagnosis of advanced melanoma with newly diagnosed, untreated,

brain metastases and controlled extra cranial disease, which per the multi-disciplinary team

decision do not require immediate radiotherapy, surgery, or standard systemic chemotherapy.

malignant glioma study arm of the expansion phase:

with histologically proven glioma grade IV, which were progressive following first line treatment

with surgery or biopsy followed by fractionated radiotherapy with concurrent temozolomide

as chemotherapy.

with recurrent histologically confirmed malignant (WHO grade III and IV) glioma or histologically

confirmed low-grade (WHO grade II) glioma with radiographic evidence of malignant transformation

by MRI, that were refractory to standard therapy, or for whom no standard therapy exists

or did not require immediate standard therapy per the multi- disciplinary team decision.

in both groups should have stable and decreasing dosage of steroids (e.g.

dexamethasone)

for a minimum of 7 days prior to baseline MRI.

Non-enzyme inducing antiepileptic drugs

the single agent dose-escalation phase, patients eligible for the study were assigned to a dose level cohort.

The starting dose was 5

mg/m 2 , which was equal to 1/10 of the human equivalent dose of the LD10 of 2X-111 in rats.

Dose levels for subsequent cohorts

were 10, 20, 30 mg/m 2 and steps of 10 mg/m 2 thereafter.

Patients received a single IV dose of 2X-111 on day 1 of

To minimize the risk of infusion reactions 5% of the total dose of 2B3-101 (in mg) was infused slowly over the first 30 minutes.

If tolerated, the infusion was completed over the next hour for a total infusion time of 90 minutes.

Each treatment cycle consisted of

the combination with trastuzumab dose-escalation phase, patients were assigned to a 2X-111 dose level cohort.

The starting dose of 2X-111

was 40 mg/m 2 every 3 weeks.

This dose has been selected based upon safety information from patients treated with 2X-111 at

this dose level, as well as upon previous treatment with PEGylated liposomal doxorubicin in combinations trastuzumab.

both cases, dose-escalation was conducted in steps of 10 mg/m 2 up to the MTD level determined for 2X-111 as single agent.

The trastuzumab dose remained fixed to a loading dose of 8 mg/kg at day 1 and 6 mg/kg every 3 weeks at the subsequent cycles throughout

the determination of the MTD.

All patients received a single IV dose of 2X-111 on day 1 of each cycle.

To minimize the risk of infusion

reactions 5% of the total dose of 2X-111 (in mg) was infused slowly over the first 30 minutes.

If 2X-111 was well tolerated, the remaining

95% of the infusion thereafter were administered over the next 60 min, resulting in a total infusion time of 90 minutes.

of trastuzumab followed 30 minutes after the completion of the 2B3-101 infusion.

the breast cancer brain metastases study arm of the expansion phase, each treatment cycle equally also consisted of 21 days.

day 1 of each cycle patients received a single IV 50 mg/m 2 dose of 2X-111 as single agent, or a dose of 2X-111 at the MTD

of 2B3-101 in combination with trastuzumab (if different).

To minimize the risk of infusion reactions 5% of the total dose (in mg) was

infused slowly over the first 30 minutes.

If 2X-111 was well tolerated, the remaining 95% of the infusion was thereafter administered

over the next 60 minutes, resulting in a total infusion time of 90 minutes.

A trastuzumab infusion followed 30 minutes after the completion

of the 2X-111 infusion, if applicable.

Each treatment cycle consisted of 21 days.

the SCLC brain metastases study arm of the expansion phase, each treatment cycle also consisted of 21 days.

Patients received a

single IV 50 mg/m 2 dose of 2X-111 on day 1 of each cycle.

To minimize the risk of infusion reactions 5% of the total dose

of 2X-111 (in mg) was infused slowly over the first 30 minutes.

If 2X-111 was well tolerated, the remaining 95% of the infusion thereafter

were administered over the next 60 min, resulting in a total infusion time of 90 minutes.

The infusion of trastuzumab followed 30 minutes

after the completion of the 2B3-101 infusion.

In the breast cancer brain

metastases study arm of the expansion phase, each treatment cycle equally also consisted of 21 days.

On day 1 of each cycle patients

received a single IV 50 mg/m 2 dose of 2X-111 as single agent, or a dose of 2X-111 at the MTD of 2B3-101 in combination with

trastuzumab (if different).

To minimize the risk of infusion reactions 5% of the total dose (in mg) was infused slowly over the first

If 2X-111 was well tolerated, the remaining 95% of the infusion was thereafter administered over the next 60 minutes, resulting

in a total infusion time of 90 minutes.

A trastuzumab infusion followed 30 minutes after the completion of the 2X-111 infusion, if applicable.

If tolerated, the infusion was then completed over the next hour for

a total infusion time of 90 minutes.

Each treatment cycle consisted of 21 days.

In the SCLC brain metastases

study arm of the expansion phase, each treatment cycle also consisted of 21 days.

Patients received a single IV 50 mg/m 2

dose of 2X-111 on day 1 of each cycle.

To minimize the risk of infusion reactions 5% of the total dose of 2X-111 (in mg) was infused slowly

over the first 30 minutes.

If tolerated, the infusion was then completed over the next hour for a total infusion time of 90 minutes.

treatment cycle consisted of 21 days.

In the melanoma brain metastases

study arm of the expansion phase, each treatment cycle also consisted of 21 days.

Patients received a single IV 50 mg/m 2

dose of 2X-111 on day 1 of each cycle.

To minimize the risk of infusion reactions 5% of the total dose of 2X-111 (in mg) was infused slowly

over the first 30 minutes.

If tolerated, the infusion was completed over the next hour for a total infusion time of 90 minutes.

Each treatment

cycle consisted of 21 days.

In the recurrent malignant

glioma study arm of the expansion phase, each treatment cycle consists of 28 days.

Patients received a single IV 60 mg/m 2

dose of 2X-111 on day 1 of each cycle.

To minimize the risk of infusion reactions 5% of the total dose of 2X-111 (in mg) was infused slowly

over the first 30 minutes.

If tolerated, the infusion was completed over the next hour for a total infusion time of 90 minutes.

Each treatment

cycle consisted of 28 days.

Infusion or hypersensitivity

reactions were expected with the first or subsequent dose of 2X-111 and/or trastuzumab.

In case of an infusion reaction, it was recommended

to follow the below infusion scheme not only for the continued infusion but also for all future infusions with 2X-111 in the patients

that experience such a reaction:

(Re)-start the 2X-111 infusion with 10 mL/hour for the first 15 minutes and increase the infusion rate every 15 to 30 minutes as follows:

20 mL/hour, 50 mL/hour, 100 mL/hour and finally 200 mL/hour.

In addition, (pre) medication such as hydrocortisone, ranitidine, cimetidine, antiemetics, and diphenhydramine in line with existing local institutional guidelines all were allowed.

Patients who received 2X-111

in combination with trastuzumab participated in an intensified cardiac program including ECG, LVEF, cTnT and NT-proBNP measurements before

start of every treatment cycle.

The following table summarizes

the demographic characteristics of patients enrolled in each of the DEP and EPP stages:

the melanoma brain metastases study arm of the expansion phase, each treatment cycle also consisted of 21 days.

Patients received

a single IV 50 mg/m 2 dose of 2X-111 on day 1 of each cycle.

To minimize the risk of infusion reactions 5% of the total dose

of 2X-111 (in mg) was infused slowly over the first 30 minutes.

If tolerated, the infusion was completed over the next hour for a total

infusion time of 90 minutes.

Each treatment cycle consisted of 21 days.

the recurrent malignant glioma study arm of the expansion phase, each treatment cycle consists of 28 days.

Patients received a single

IV 60 mg/m 2 dose of 2X-111 on day 1 of each cycle.

To minimize the risk of infusion reactions 5% of the total dose of 2X-111

(in mg) was infused slowly over the first 30 minutes.

If tolerated, the infusion was completed over the next hour for a total infusion

time of 90 minutes.

Each treatment cycle consisted of 28 days.

or hypersensitivity reactions were expected with the first or subsequent dose of 2X-111 and/or trastuzumab.

In case of an infusion reaction,

it was recommended to follow the below infusion scheme not only for the continued infusion but also for all future infusions with 2X-111

in the patients that experience such a reaction:

(Re)-start the 2X-111 infusion

with 10 mL/hour for the first 15 minutes and increase the infusion rate every 15 to 30 minutes as follows:

20 mL/hour, 50 mL/hour,

100 mL/hour and finally 200 mL/hour.

In addition, (pre) medication

such as hydrocortisone, ranitidine, cimetidine, antiemetics, and diphenhydramine in line with existing local institutional guidelines

all were allowed.

who received 2X-111 in combination with trastuzumab participated in an intensified cardiac program including ECG, LVEF, cTnT and NT-proBNP

measurements before start of every treatment cycle.

following table summarizes the demographic characteristics of patients enrolled in each of the DEP and EPP stages:

Characteristic

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Estrogen receptor on BC (N)

Preliminary anti-cancer activity

for solid tumors was assessed according to RECIST 1.1 criteria.

The preliminary anti-cancer activity for recurrent malignant gliomas was

assessed according to the RANO criteria.

In order to evaluate the anti-cancer activity of the treatment, appropriate imaging procedures

were performed to accurately assess the tumor size at baseline, at the last day (day 21 or in case of patients with recurrent malignant

glioma enrolled in the dose expansion phase day 28) of every even cycle (e.g.

cycle 2, 4, 6 etc.), and at withdrawal from study treatment.

Unless not done within 14 days before start of treatment the MRI of the brain was performed to assess brain lesion sizes.

not done within 28 days before baseline, a CT/MRI-scan of chest/abdomen/pelvis was performed to assess solid tumor sizes.

If corticosteroid

treatment (e.g.

dexamethasone or methylprednisolone) or increase in corticosteroid treatment was required between screening and the first

cycle of 2X-111, the baseline MRI was re-performed after a minimum of 7 days of stable or decreasing doses of the corticosteroids.

anti-cancer activity for solid tumors was assessed according to RECIST 1.1 criteria.

The preliminary anti-cancer activity for recurrent

malignant gliomas was assessed according to the RANO criteria.

In order to evaluate the anti-cancer activity of the treatment, appropriate

imaging procedures were performed to accurately assess the tumor size at baseline, at the last day (day 21 or in case of patients with

recurrent malignant glioma enrolled in the dose expansion phase day 28) of every even cycle (e.g.

cycle 2, 4, 6 etc.), and at withdrawal

from study treatment.

Unless not done within 14 days before start of treatment the MRI of the brain was performed to assess brain

lesion sizes.

Unless not done within 28 days before baseline, a CT/MRI-scan of chest/abdomen/pelvis was performed to assess solid

If corticosteroid treatment (e.g.

dexamethasone or methylprednisolone) or increase in corticosteroid treatment was required

between screening and the first cycle of 2X-111, the baseline MRI was re-performed after a minimum of 7 days of stable or decreasing

doses of the corticosteroids.

The first cycle of drug was not initiated until baseline MRI has been performed.

CT/MRI-scans of the chest/abdomen/pelvis

were only obtained from patients with solid tumors and brain metastases.

These assessments were not required for patients with recurrent

malignant glioma.

Identified lesions were consistently followed using the unique lesion number assigned at baseline.

All tumor measurements

were obtained using the same diagnostic procedure used at baseline.

For each course in which a tumor assessment was made, standard tumor

response criteria were applied and the response for that course documented in the patient file.

All identified lesions at screening/baseline

were followed using the same imaging procedure.

A bone scan was only obtained if clinically indicated during the study if the patient

developed symptoms or signs of bone metastases.

If bone metastases were known to be present at screening, bone scintigraphy was performed

in addition to and at the same time as the CT/MRI-scans throughout the study.

All lesions were followed during treatment (i.e.

lesions as well as non-target lesions).

All CT/MRI Images from patients enrolled in the dose expansion arms of the study were sent electronically

to a central repository system.

Safety was assessed by means

of physical examination, neurological examination (and a brain MRI if a neurological deficit was leading to WHO> 2), weight, vital

signs, ECOG performance status, MMSE, HDS, laboratory evaluations (hematology, biochemistry and urinalysis and N-terminal Pro-Brain Natriuretic

Peptide (NT-ProBNP) and cardiac Troponin T (cTnT)), electrocardiograms (ECG), LVEF (MUGA/ECHO)), and recording of concurrent illness/therapy

and adverse events.

Clinical anti-cancer activity

was assessed by best overall response (OR) by both, investigator, and computer-based methods.

Overall, both methodologies reported similar

results with the majority of best overall survival (OS) reported being stable diseases (SDs) while some partial responses (PRs) also being

In the Dose Escalation Phase

(DEP) group and in the glioma only patients, SD was the best OR recorded for 26.5% and 23.5% of the patients, as reported by the computer

and investigator, respectively.

At the same time, in the DEP group and for other solid tumors and across all single and combination arms,

one PR (2.9%) was reported by the computer in the 2X-111 50 mg/m 2 + trastuzumab group.

However, this response was deemed as

SD by the investigator.

The rate of SDs reported for this other (non-glioma) solid tumor group, was 23.3% and 20.6% for the computer and

investigator, respectively.

In the Expansion Phase (EPP)

group and for the glioma patients, both the computer and the investigator methods recorded the best OR as an SD rate of 17.8%.

solid tumors group, the same SD rate of 26.7% was reported by both methods of assessment also.

In addition, PR was also reported, 2.2%

by the investigator and 4.4% by the computer.

The following tables summarize

best overall responses by dose group and by cohort:

Dose groups in mg/m 2

Malignant Glioma

Dose groups in mg/m 2

Malignant Glioma

Finally, analysis of the three

exploratory populations revealed that SDs are the predominant best OR.

In the glioma patient group receiving 2X-111 greater or equal to

40 mg/m 2 , 16 out of the 27 patients experienced PD.

In the breast-patient-group receiving 2X-111 greater or equal to 40 mg/m 2 ,

2 out of 24 patients experienced PR according to the computer or investigator method of assessment, respectively and at the same time,

12 or 15 out of 24 experienced an SD.

In the Her2+ breast patient group receiving 2X-111 greater or equal to 40 mg/m 2 in combination

with trastuzumab, 2 or 1 out of 16 patients experienced PR according to the computer or investigator method of assessment, respectively

and at the same time, 10 or 12 out of 24 experienced an SD.

of the chest/abdomen/pelvis were only obtained from patients with solid tumors and brain metastases.

These assessments were not required

for patients with recurrent malignant glioma.

Identified lesions were consistently followed using the unique lesion number assigned at

All tumor measurements were obtained using the same diagnostic procedure used at baseline.

For each course in which a tumor

assessment was made, standard tumor response criteria were applied and the response for that course documented in the patient file.

identified lesions at screening/baseline were followed using the same imaging procedure.

A bone scan was only obtained if clinically

indicated during the study if the patient developed symptoms or signs of bone metastases.

If bone metastases were known to be present

at screening, bone scintigraphy was performed in addition to and at the same time as the CT/MRI-scans throughout the study.

were followed during treatment (i.e.

target lesions as well as non-target lesions).

All CT/MRI Images from patients enrolled in the dose

expansion arms of the study were sent electronically to a central repository system.

was assessed by means of physical examination, neurological examination (and a brain MRI if a neurological deficit was leading to WHO>

2), weight, vital signs, ECOG performance status, MMSE, HDS, laboratory evaluations (hematology, biochemistry and urinalysis and N-terminal

Pro-Brain Natriuretic Peptide (NT-ProBNP) and cardiac Troponin T (cTnT)), electrocardiograms (ECG), LVEF (MUGA/ECHO)), and recording

of concurrent illness/therapy and adverse events.

anti-cancer activity was assessed by best overall response (OR) by both, investigator, and computer-based methods.

Overall, both methodologies

reported similar results with the majority of best overall survival (OS) reported being stable diseases (SDs) while some partial responses

(PRs) also being observed.

the Dose Escalation Phase (DEP) group and in the glioma only patients, SD was the best OR recorded for 26.5% and 23.5% of the patients,

as reported by the computer and investigator, respectively.

At the same time, in the DEP group and for other solid tumors and across

all single and combination arms, one PR (2.9%) was reported by the computer in the 2X-111 50 mg/m 2 + trastuzumab group.

this response was deemed as SD by the investigator.

The rate of SDs reported for this other (non-glioma) solid tumor group, was 23.3%

and 20.6% for the computer and investigator, respectively.

the Expansion Phase (EPP) group and for the glioma patients, both the computer and the investigator methods recorded the best OR as an

SD rate of 17.8%.

In the solid tumors group, the same SD rate of 26.7% was reported by both methods of assessment also.

PR was also reported, 2.2% by the investigator and 4.4% by the computer.

following tables summarize best overall responses by dose group and by cohort:

groups in mg/m 2

analysis of the three exploratory populations revealed that SDs are the predominant best OR.

In the glioma patient group receiving 2X-111

greater or equal to 40 mg/m 2 , 16 out of the 27 patients experienced PD.

In the breast-patient-group receiving 2X-111 greater

or equal to 40 mg/m 2 , 2 out of 24 patients experienced PR according to the computer or investigator method of assessment,

respectively and at the same time, 12 or 15 out of 24 experienced an SD.

In the Her2+ breast patient group receiving 2X-111 greater or

equal to 40 mg/m 2 in combination with trastuzumab, 2 or 1 out of 16 patients experienced PR according to the computer or investigator

method of assessment, respectively and at the same time, 10 or 12 out of 24 experienced an SD.

The following table summarizes those results:

Dose groups in mg/m 2 > = 40 mg

groups in mg/m 2 > = 40 mg

Malignant Glioma

All patients have reported

at least one treatment emergent adverse event (grade I to IV) but all of them were manageable and none of them have been considered unexpected

based on the previous experience from treatment with liposomal doxorubicin (Doxil/Caelyx) and/or non-clinical safety information

with Allarity.

The number of infusions administered

as single agent or in combination with trastuzumab to the individual patients ranged from 1 to 10.

Long-term toxicity data (> 2 infusions

of 2X-111) were available from 34 patients, all but one of these patients were treated with doses more or equal to 40 mg/m 2 .

patients have reported at least one treatment emergent adverse event (grade I to IV) but all of them were manageable and none of them

have been considered unexpected based on the previous experience from treatment with liposomal doxorubicin (Doxil/Caelyx) and/or

non-clinical safety information with Allarity.

number of infusions administered as single agent or in combination with trastuzumab to the individual patients ranged from 1 to 10.

toxicity data (> 2 infusions of 2X-111) were available from 34 patients, all but one of these patients were treated with doses more

or equal to 40 mg/m 2 .

One patient has received 10 infusions.

The maximum total dose of 2X-111 delivered to date is 240 mg/m 2 .

Following treatment

with 2X-111 infusion related reactions were reported in 27% of the patients in the Dose Escalation and 34% in the EPP.

All infusion related

reactions (dyspnea, chest pain, back pain, fatigue, headache, flushing, chills, tachycardia) that were observed in this study with 2X-111

were in between grade 1 to 3, but no grade 4 reactions.

After modification of the initial infusion rate (5% given over the first 30 min

and the remaining 95% over 60 min) at a dose of 30 mg/m 2 , infusion reaction grade 1-2 has been reduced and reported in 16 out

of 68 treated patients (23%), the majority still without any premedication.

In all patients experiencing an infusion reaction the infusions

were continued after a shorter treatment interruption.

Only one case was reported as SAE (grade 2 bronchospasm).

With respect to hematological

toxicity, neutropenia was observed in 40.5%, leukocytopenia in 24.3% and thrombocytopenia in 18.9% of patients in the DEP.

In EPP neutropenia

occurred in 31.9%, leukocytopenia in 8.5% and thrombocytopenia in 4.3% of patients.

In all patients with hematologic side effects the

subsequent dose has been withheld for 1-2 weeks, per protocol and in 1 case also a dose reduction by 10 mg/m 2 .

Palmar plantar erythrodysthesia

(PPE) was reported in 45.9% of patients in DEP and 55.3% in EPP.

However, no hand-foot syndrome grade 4 or 5 was reported.

Grade 3 hand-foot

syndrome was present in approximately 21.6% in DEP and 23.4% in EPP.

While hand-foot syndrome caused by 2X-111 was reversible within one

or two weeks, it caused dose delays and dose reductions in several patients.

However, a favorable safety profile was observed and 2X-111

was relatively well tolerated in both patients with BCBM from solid tumors and patients with recurrent malignant gliomas.

Overview of Glioblastoma Multiforme (GBM)

Malignant brain tumors account

for approximately 190,000 new cases and 40,000 deaths per year globally.

In the U.S., gliomas account for 81% of all malignant brain tumors

where glioblastoma (GBM) (WHO grade IV) is the most aggressive form and represents the most prevalent (54%) form of all gliomas and 46%

of all primary malignant brain tumors.

The majority of GBM (95%) has histologically been classified as primary GBM mostly in elderly without

any clinical history of lower grade gliomas.

Secondary GBM develops from lower grade gliomas in younger patients (age <45 years)

in the course of many months to years of disease.

Today the distinction is based on isocitrate dehydrogenase (IDH) mutations.

The prognosis of newly diagnosed

GBM is poor with overall survival (OS) rates in the U.S.

at 1-year, 2-year, and 5-year survival of 37.2%, 8.8%, and 5.1%, respectively.

The current standard of care is tumor resection followed by radiotherapy combined with chemotherapy with temozolomide (TMZ) and then continuing

with TMZ maintenance, and results in median OS of 14.6 months, which does not seem to have been relevantly improved over the past several

Following treatment with 2X-111 infusion related reactions were reported in 27% of the patients in the Dose Escalation and 34% in the

All infusion related reactions (dyspnea, chest pain, back pain, fatigue, headache, flushing, chills, tachycardia) that were observed

in this study with 2X-111 were in between grade 1 to 3, but no grade 4 reactions.

After modification of the initial infusion rate (5%

given over the first 30 min and the remaining 95% over 60 min) at a dose of 30 mg/m 2 , infusion reaction grade 1-2 has been

reduced and reported in 16 out of 68 treated patients (23%), the majority still without any premedication.

In all patients experiencing

an infusion reaction the infusions were continued after a shorter treatment interruption.

Only one case was reported as SAE (grade 2

bronchospasm).

With respect to hematological toxicity, neutropenia was observed in 40.5%, leukocytopenia in 24.3% and thrombocytopenia

in 18.9% of patients in the DEP.

In EPP neutropenia occurred in 31.9%, leukocytopenia in 8.5% and thrombocytopenia in 4.3% of patients.

In all patients with hematologic side effects the subsequent dose has been withheld for 1-2 weeks, per protocol and in 1 case also a

dose reduction by 10 mg/m 2 .

plantar erythrodysthesia (PPE) was reported in 45.9% of patients in DEP and 55.3% in EPP.

However, no hand-foot syndrome grade 4 or 5

was reported.

Grade 3 hand-foot syndrome was present in approximately 21.6% in DEP and 23.4% in EPP.

While hand-foot syndrome caused

by 2X-111 was reversible within one or two weeks, it caused dose delays and dose reductions in several patients.

However, a favorable

safety profile was observed and 2X-111 was relatively well tolerated in both patients with BCBM from solid tumors and patients with recurrent

malignant gliomas.

of Glioblastoma Multiforme (GBM)

brain tumors account for approximately 190,000 new cases and 40,000 deaths per year globally.

In the U.S., gliomas account for 81% of

all malignant brain tumors where glioblastoma (GBM) (WHO grade IV) is the most aggressive form and represents the most prevalent (54%)

form of all gliomas and 46% of all primary malignant brain tumors.

The majority of GBM (95%) has histologically been classified as primary

GBM mostly in elderly without any clinical history of lower grade gliomas.

Secondary GBM develops from lower grade gliomas in younger

patients (age <45 years) in the course of many months to years of disease.

Today the distinction is based on isocitrate dehydrogenase

(IDH) mutations.

prognosis of newly diagnosed GBM is poor with overall survival (OS) rates in the U.S.

at 1-year, 2-year, and 5-year survival of 37.2%,

8.8%, and 5.1%, respectively.

The current standard of care is tumor resection followed by radiotherapy combined with chemotherapy with

TMZ and then continuing with TMZ maintenance, and results in median OS of 14.6 months, which does not seem to have been relevantly improved

over the past several decades.

Thus, the therapeutic results are still not satisfactory, and new and more efficacious therapies are needed.

Only a subgroup

of GBM patients (approximately 32%), who have a methylated MGMT (O6-methylguanine-DNA methyltransferase) promotor, may benefit from TMZ

The MGMT gene is involved in DNA repair, and epigenetic silencing by promotor methylation has previously been shown to be associated

with longer survival in patients receiving alkylating agents.

It has been shown that TMZ treatment improves OS from 15.3 to 21.7 months

in patients with MGMT silencing, while patients with unmethylated MGMT promotors had no significant benefit from TMZ.

In most GBM patients the disease

will progress sooner or later, however there is no clear recommendations for second line treatment.

Depending on the clinical picture

of each individual patient the treatment of recurrent GBM includes a second surgical procedure with or without implantation of carmustine

wafers, nitrosoureas, TMZ treatment, the VEGF-blocking antibody bevacizumab (Avastin ® ) alone or in combination with the

topoisomerase 1 inhibitor irinotecan, and, in some countries, systemic chemotherapy (e.g.

carmustine plus irinotecan).

In a Danish study

of bevacizumab in combination with irinotecan an overall response rate (ORR) of 30%, median PFS of 5 months, and median OS of 7.5 months

was observed.

Only a subgroup of GBM patients (approximately 32%), who have a methylated MGMT (O6-methylguanine-DNA methyltransferase) promotor, may

benefit from TMZ treatment.

The MGMT gene is involved in DNA repair, and epigenetic silencing by promotor methylation has previously

been shown to be associated with longer survival in patients receiving alkylating agents.

It has been shown that TMZ treatment improves

OS from 15.3 to 21.7 months in patients with MGMT silencing, while patients with unmethylated MGMT promotors had no significant benefit

most GBM patients the disease will progress sooner or later, however there is no clear recommendations for second line treatment.

on the clinical picture of each individual patient the treatment of recurrent GBM includes a second surgical procedure with or without

implantation of carmustine wafers, nitrosoureas, TMZ treatment, the VEGF-blocking antibody bevacizumab (Avastin ® ) alone

or in combination with the topoisomerase 1 inhibitor irinotecan, and, in some countries, systemic chemotherapy (e.g.

carmustine plus

In a Danish study of bevacizumab in combination with irinotecan an overall response rate (ORR) of 30%, median PFS of 5 months,

and median OS of 7.5 months was observed.

However, the treatment options for recurrent GBM are limited and the prognosis is poor.

Patients should therefore be encouraged

to participate in clinical trials.

Rationale for Liposomal Doxorubicin in GBM

Several studies on established

glioma cell lines have shown promising levels of therapeutic activity of doxorubicin.

In the last decade, treatment of GBM with pegylated

liposomal doxorubicin (Doxil ® /Caelyx ® ) has been assessed in three small studies.

The treatment has been

shown to result in a modest positive effect (1.5 months) on survival.

However, this effect has not been considered sufficient to justify

the use of Doxil ® /Caelyx ® as a standard treatment option in patients with brain tumors according to treating

clinicians and regulatory agencies.

Existing PEG-liposomal formulations

of doxorubicin, such as Doxil ® /Caelyx ® , do not readily pass the BBB and therefore do not deliver sufficient

levels of the drug to brain tumors in order to provide meaningful therapeutic benefit.

Likewise, doxorubicin itself does not pass the

The FDA granted orphan drug

designation for 2X-111 for the treatment of glioma on August 16, 2010 (FDA/103119).

Additionally, on September 21, 2010, the orphan drug

designation of 2X-111 for the treatment of glioma was approved by the EMA (EMA/OD/031/10).

2X-111 is a novel PEG-liposomal

formulation of doxorubicin, which, by virtue of the glutathione modification on the liposomal surface, can pass the BBB and deliver therapeutically

sufficient levels of doxorubicin to brain tumors.

Accordingly, 2X-111 has the potential to be a new and beneficial therapeutic option

for the treatment of GBM.

Rationale for Liposomal Doxorubicin in Breast

Cancer (Brain Metastases)

Brain metastases are diagnosed

in approximately 15% of unselected patients with advanced breast cancer.

Over time, it has become increasingly clear that the biology

of the primary tumor influences the pattern of metastatic spread, including the likelihood of relapse in the central nervous system (CNS).

As many as half of patients with HER2-positive advanced breast cancer will develop brain metastases at some point in the course of their

Within the HER2-positive subset,

hormone receptor status appears to further define the risk of CNS relapse, with patients having hormone receptor-negative/HER2-positive

should therefore be encouraged to participate in clinical trials.

for Liposomal Doxorubicin in GBM

studies on established glioma cell lines have shown promising levels of therapeutic activity of doxorubicin.

In the last decade, treatment

of GBM with pegylated liposomal doxorubicin (Doxil ® /Caelyx ® ) has been assessed in three small studies.

The treatment has been shown to result in a modest positive effect (1.5 months) on survival.

However, this effect has not been considered

sufficient to justify the use of Doxil ® /Caelyx ® as a standard treatment option in patients with brain tumors

according to treating clinicians and regulatory agencies.

PEG-liposomal formulations of doxorubicin, such as Doxil ® /Caelyx ® , do not readily pass the BBB and therefore

do not deliver sufficient levels of the drug to brain tumors in order to provide meaningful therapeutic benefit.

Likewise, doxorubicin

itself does not pass the BBB.

FDA granted orphan drug designation for 2X-111 for the treatment of glioma on August 16, 2010 (FDA/103119).

Additionally, on September

21, 2010, the orphan drug designation of 2X-111 for the treatment of glioma was approved by the EMA (EMA/OD/031/10).

is a novel PEG-liposomal formulation of doxorubicin, which, by virtue of the glutathione modification on the liposomal surface, can pass

the BBB and deliver therapeutically sufficient levels of doxorubicin to brain tumors.

Accordingly, 2X-111 has the potential to be a new

and beneficial therapeutic option for the treatment of GBM.

for Liposomal Doxorubicin in Breast Cancer (Brain Metastases)

metastases are diagnosed in approximately 15% of unselected patients with advanced breast cancer.

Over time, it has become increasingly

clear that the biology of the primary tumor influences the pattern of metastatic spread, including the likelihood of relapse in the central

nervous system (CNS).

As many as half of patients with HER2-positive advanced breast cancer will develop brain metastases at some point

in the course of their disease.

the HER2-positive subset, hormone receptor status appears to further define the risk of CNS relapse, with patients having hormone receptor-negative/HER2-positive

tumors experiencing increased risk developing metastases in the CNS as the first site of relapses, compared with patients with hormone

6 unchanged sentences

to experience a shorter time to relapses in the CNS compared to patients with luminal tumors.

In a historical series of

unselected patients with breast cancer brain metastases treated with whole-brain radiotherapy (WBRT), the median survival has been reported

to be approximately five to six months.

More recent analyses have identified performance status of the patient and the biologic tumor

subtype as major drivers of prognosis.

For example, in a multi-institutional retrospective database of over 400 patients with breast cancer

brain metastases, a prognostic model (the Diagnosis-Specific Graded Prognostic Assessment, DSGPA) using these factors (plus age) was able

to distinguish between patients experiencing a two-year median survival versus those with 3.4 months median survival.

Across multiple retrospective

studies, the most striking differences consistently noted have been between patients with HER2-positive breast cancer (who carry the most

favorable prognosis) and patients with triple-negative breast cancer.

Based on several lines of evidence, it is likely that improved systemic

tumor control is a major contributing factor to this difference.

First, although one must interpret retrospective data cautiously because

of issues with patient selection, it has been observed by multiple investigators that patients with HER2-positive tumors who continue

anti-HER2 therapy following the diagnosis of brain metastases do far better than those who receive either no therapy, or chemotherapy

without HER2-directed therapy.

Second, as many as half of the patients with HER2-positive brain metastases die primarily from CNS progression

of their disease (as opposed to systemic progression).

Accordingly, the need for a brain-targeted therapy for the treatment of brain metastases

is warranted in this patient population.

This is distinguished from patients with triple-negative brain metastases, where patients most

commonly die of uncontrolled systemic disease.

Existing PEG-liposomal formulations

of doxorubicin, such as Doxil ® /Caelyx ® , do not readily pass the BBB and therefore do not deliver sufficient

levels of the drug to brain tumors in order to provide meaningful therapeutic benefit.

Likewise, doxorubicin itself does not pass the

2X-111 is a novel PEG-liposomal

formulation of doxorubicin, which, by virtue of the glutathione modification on the liposomal surface, can pass the BBB and deliver therapeutically

sufficient levels of doxorubicin to brain tumors.

Accordingly, 2X-111 has the potential to a new and beneficial therapeutic option for

the treatment of brain metastases of breast cancer.

Future Opportunities & Development

Plans for 2X-111

In June of 2020, we out-licensed

our 2X-111 program to Smerud Medical Research International, our long-time CRO partner in Europe, which was subsequently terminated on

March 28, 2022.

a historical series of unselected patients with breast cancer brain metastases treated with whole-brain radiotherapy (WBRT), the median

survival has been reported to be approximately five to six months.

More recent analyses have identified performance status of the patient

and the biologic tumor subtype as major drivers of prognosis.

For example, in a multi-institutional retrospective database of over 400

patients with breast cancer brain metastases, a prognostic model (the Diagnosis-Specific Graded Prognostic Assessment, DSGPA) using these

factors (plus age) was able to distinguish between patients experiencing a two-year median survival versus those with 3.4 months median

multiple retrospective studies, the most striking differences consistently noted have been between patients with HER2-positive breast

cancer (who carry the most favorable prognosis) and patients with triple-negative breast cancer.

Based on several lines of evidence,

it is likely that improved systemic tumor control is a major contributing factor to this difference.

First, although one must interpret

retrospective data cautiously because of issues with patient selection, it has been observed by multiple investigators that patients

with HER2-positive tumors who continue anti-HER2 therapy following the diagnosis of brain metastases do far better than those who receive

either no therapy, or chemotherapy without HER2-directed therapy.

Second, as many as half of the patients with HER2-positive brain metastases

die primarily from CNS progression of their disease (as opposed to systemic progression).

Accordingly, the need for a brain-targeted

therapy for the treatment of brain metastases is warranted in this patient population.

This is distinguished from patients with triple-negative

brain metastases, where patients most commonly die of uncontrolled systemic disease.

PEG-liposomal formulations of doxorubicin, such as Doxil ® /Caelyx ® , do not readily pass the BBB and therefore

do not deliver sufficient levels of the drug to brain tumors in order to provide meaningful therapeutic benefit.

Likewise, doxorubicin

itself does not pass the BBB.

is a novel PEG-liposomal formulation of doxorubicin, which, by virtue of the glutathione modification on the liposomal surface, can pass

the BBB and deliver therapeutically sufficient levels of doxorubicin to brain tumors.

Accordingly, 2X-111 has the potential to a new

and beneficial therapeutic option for the treatment of brain metastases of breast cancer.

Opportunities & Development Plans for 2X-111

June of 2020, we out-licensed our 2X-111 program to Smerud Medical Research International, our long-time CRO partner in Europe, which

was subsequently terminated on March 28, 2022.

Allarity, SMERUD, and original drug owner 2BBB Medicines, B.V.

are currently negotiating a revised agreement under which

SMERUD will secure grant funding to advance this program, with DRP ® companion diagnostic support from Allarity.

DRP ® Companion Diagnostic for

We anticipate that 2X-111

will be developed together with our retrospectively validated DRP ® companion diagnostic for doxorubicin, which enables

us to select the patients most likely to respond to the drug in our clinical trials.

The FDA has previously approved our IDE applications

for use of our DRP ® companion diagnostics in clinical trials of two of our priority programs:

are currently negotiating

a revised agreement under which SMERUD will secure grant funding to advance this program, with DRP ® companion diagnostic

support from Allarity.

Companion Diagnostic for 2X-111

anticipate that 2X-111 will be developed together with our retrospectively validated DRP ® companion diagnostic for doxorubicin,

which enables us to select the patients most likely to respond to the drug in our clinical trials.

The FDA has previously approved our

IDE applications for use of our DRP ® companion diagnostics in clinical trials of two of our priority programs:

Stenoparib and LiPlaCis ® .

Accordingly, we are confident the FDA will approve an eventual IDE for our Doxorubicin-DRP ® companion diagnostic

Accordingly, we are confident the FDA will approve an eventual IDE for our Doxorubicin-DRP ®

companion diagnostic for U.S.

clinical trials of 2X-111.

The Doxorubicin-DRP ® , which comprises 299 expressed genes, was initially developed

using gene expression data from the National Cancer Institute NCI60 cancer cell lines panel.

The putative Doxorubicin-DRP ® ,

developed through our DRP ® platform using gene expression data from cancer cell line testing data, was retrospectively

validated using biopsy materials from the screening of breast cancer patients for our LiPlaCis ® trial (clinicaltrial.gov

number NCT01861496).

The Doxorubicin-DRP ® , which comprises 299 expressed

genes, was initially developed using gene expression data from the National Cancer Institute NCI60 cancer cell lines panel.

putative Doxorubicin-DRP ® , developed through our DRP ® platform using gene expression data from cancer cell

line testing data, was retrospectively validated using biopsy materials from the screening of breast cancer patients for our LiPlaCis ®

trial (clinicaltrial.gov number NCT01861496).

A total of 140 patients received epirubicin and were included in the analysis.

The study population was diagnosed

with primary BC between 1986 and 2015 and received epirubicin in the locally advanced or metastatic setting between May 1997 and

November 2016.

The hazard ratio for DRP scores differing by 50 percentage points was 0.55 (95% CI –0.93, one-sided).

were published in Breast Cancer Res Treat.

In sum, our retrospectively

validated Doxorubicin-DRP ® companion diagnostic correctly identifies responder patients to 2X-111 and we expect this DRP ®

companion diagnostic will be used for all clinical programs to advance 2X-111.

Existing Liposomal Doxorubicin Drugs &

Our Opportunity

There has not been a therapeutically

meaningful new drug for the treatment of GBM since bevacizumab (Avastin ® ) was approved, by the FDA, in 2009 as a monotherapy

for patients who have progressed on prior therapy.

Prior to introduction of bevacizumab in the GBM treatment landscape, TMZ was approved,

by the FDA in 2005, for the treatment of adult patients with newly diagnosed GBM concomitantly with radiotherapy and then as maintenance

Nearly 20 years later, TMZ remains the only front-line therapy for GBM, and its effectiveness is limited.

Similarly, the

effectiveness of benefit of second-line therapeutic bevacizumab remains limited.

Accordingly, there is pressing need for new and innovative

therapies for the treatment of this aggressive and incurable cancer.

There is no currently approved,

available therapy for the treatment of brain metastases of breast cancer, and these metastases remain fatal to breast cancer patients.

Accordingly, there is pressing need for new and innovative therapies for the treatment of this aggressive and incurable metastatic cancer.

Worldwide annual sales TMZ

exceeded $1 billion annually in 2009.

The global GBM drugs market to projected to reach nearly $1.8 billion by 2027, expanding at a CAGR

of 12.8% during the forecast period, driven by rising geriatric population, growing incidence cases and clinical pipeline of new products.

The global breast cancer therapeutics market has been valued at over $19 billion in 2018 and is expected to reach over $40 billion by

the year 2026, at a CAGR of 10.6%.

Since an estimated 10-15% of breast cancer patients will develop brain metastases, which are fatal,

the estimated annual market for new therapeutics to treat such brain metastases will exceed $4 billion by 2026.

While there are several approved

PEG-liposomal doxorubicin formulations (e.g.

Doxil ® /Caelyx ® ) currently marketed for the treatment of numerous

cancer, including breast cancer, these drugs do not pass the BBB.

There are currently no approved, targeted liposomal formulations of

doxorubicin on the market that are capable of passing the BBB and therefore treating both primary and secondary brain tumors.

2X-111 has the potential to be a novel, beneficial product with the potential, together with its DRP ® companion diagnostic,

to gain substantial market share not only in GBM and breast cancer (brain metastases) but as a new therapy for the numerous other primary

and second brain tumors.

Overview of Our Prior Therapeutic Candidate

Irofulven (DNA damaging agent) and Our Out-licensed Putative DRP ® Companion Diagnostic

Mechanisms of Action

Irofulven (6-hydroxymethylacylfulvene)

is a unique DNA damaging agent that is a semi-synthetic sesquiterpene derivative of illudin S, a natural toxin isolated from the Jack

O’lantern mushroom ( Omphalotus illudens ).

Irofulven has two primary anti-tumor mechanisms of action:

first, it produces bulky

single strand DNA adducts that are only repairable by the transcription coupled nucleotide excision repair (TC-NER) pathway;

it stalls RNA polymerase II leading to transcription and cell cycle arrest and apoptosis.

Irofulven is a prodrug.

active metabolite is created by the reduction of the unsaturated α−β ketone by the NADPH-dependent Prostaglandin Reductase

study population was diagnosed with primary BC between 1986 and 2015 and received epirubicin in the locally advanced or metastatic setting

between May 1997 and November 2016.

The hazard ratio for DRP scores differing by 50 percentage points was 0.55 (95% CI –0.93,

The results were published in Breast Cancer Res Treat.

sum, our retrospectively validated Doxorubicin-DRP ® companion diagnostic correctly identifies responder patients to 2X-111

and we expect this DRP ® companion diagnostic will be used for all clinical programs to advance 2X-111.

Liposomal Doxorubicin Drugs & Our Opportunity

has not been a therapeutically meaningful new drug for the treatment of GBM since bevacizumab (Avastin ® ) was approved,

by the FDA, in 2009 as a monotherapy for patients who have progressed on prior therapy.

Prior to introduction of bevacizumab in the GBM

treatment landscape, TMZ was approved, by the FDA in 2005, for the treatment of adult patients with newly diagnosed GBM concomitantly

with radiotherapy and then as maintenance treatment.

Nearly 20 years later, TMZ remains the only front-line therapy for GBM, and

its effectiveness is limited.

Similarly, the effectiveness of benefit of second-line therapeutic bevacizumab remains limited.

there is pressing need for new and innovative therapies for the treatment of this aggressive and incurable cancer.

is no currently approved, available therapy for the treatment of brain metastases of breast cancer, and these metastases remain fatal

to breast cancer patients.

Accordingly, there is pressing need for new and innovative therapies for the treatment of this aggressive

and incurable metastatic cancer.

annual sales TMZ exceeded $1 billion annually in 2009.

The global GBM drugs market to projected to reach nearly $1.8 billion by 2027,

expanding at a CAGR of 12.8% during the forecast period, driven by rising geriatric population, growing incidence cases and clinical

pipeline of new products.

The global breast cancer therapeutics market has been valued at over $19 billion in 2018 and is expected to

reach over $40 billion by the year 2026, at a CAGR of 10.6%.

Since an estimated 10-15% of breast cancer patients will develop brain metastases,

which are fatal, the estimated annual market for new therapeutics to treat such brain metastases will exceed $4 billion by 2026.

there are several approved PEG-liposomal doxorubicin formulations (e.g.

Doxil ® /Caelyx ® ) currently marketed

for the treatment of numerous cancer, including breast cancer, these drugs do not pass the BBB.

There are currently no approved, targeted

liposomal formulations of doxorubicin on the market that are capable of passing the BBB and therefore treating both primary and secondary

brain tumors.

Accordingly, 2X-111 has the potential to be a novel, beneficial product with the potential, together with its DRP ®

companion diagnostic, to gain substantial market share not only in GBM and breast cancer (brain metastases) but as a new therapy

for the numerous other primary and second brain tumors.

of Our Prior Therapeutic Candidate Irofulven (DNA damaging agent) and Our Out-licensed Putative DRP ® Companion Diagnostic

(DELETE WHOLE SECTION?)

(6-hydroxymethylacylfulvene) is a unique DNA damaging agent that is a semi-synthetic sesquiterpene derivative of illudin S, a natural

toxin isolated from the Jack O’lantern mushroom ( Omphalotus illudens ).

Irofulven has two primary anti-tumor mechanisms of

first, it produces bulky single strand DNA adducts that are only repairable by the transcription coupled nucleotide excision

repair (TC-NER) pathway;

and second, it stalls RNA polymerase II leading to transcription and cell cycle arrest and apoptosis.

is a prodrug.

The active metabolite is created by the reduction of the unsaturated α−β ketone by the NADPH-dependent

Prostaglandin Reductase 1 (PTGR1).

This metabolite is unstable and highly reactive, binding to either protein or DNA.

The DNA binding is primarily to the 3-N

of deoxyadenosine (98%) with the remainder binding to 7-N deoxyguanine.

The resulting bulky single strand adducts can cause single strand

DNA breaks and S-phase double strand DNA breaks.

The GG-NER, BER and MMR pathways do not detect or remove Irofulven-DNA adducts, which

either persist into, or are created during, S-phase of cancer cell duplication and create double strand DNA breaks which may be repaired

by Homologous Recombination.

Irofulven is more active in

vitro against tumor cells of epithelial origin and is more resistant than other alkylating agents to deactivation by p53 loss and

Irofulven showed impressive anticancer results in xenograft models, shows synergy with topoisomerase I inhibitors, and has demonstrated

activity against cell lines that are resistant to other therapies.

Irofulven has significant scope for combination with other therapies,

including PARP inhibitors, checkpoint inhibitors (e.g.

PD-1 inhibitors) and standard chemotherapeutic regimes, and is synergistic with

other therapies targeting the TC-NER pathway and other DNA damage pathways.

Irofulven causes apoptosis

in sensitive tumor cell lines.

Activation of caspases 3, 7, 8, and 9 has been well documented in Irofulven-treated tumor cell lines.

also causes upregulation of ATM/Chk2 and ATR-dependent FANCD2 mono-ubiquitination.

In all cases, however, the functional linkage(s) between

irofulven adducts (both DNA and protein) and subsequent pathway activation steps are, at present, not fully understood.

DRP ® -Guided Phase 2 Clinical

Prior to July 23, 2021, and

our sale of Irofulven to Lantern Pharma, Inc., we commenced a DRP ® -guided Phase 2 clinical trial of Irofulven in androgen

receptor (AR)-targeted and Docetaxel-Pre-treated Metastatic Castration-Resistant Prostate Cancer (mCRPC) patients using our putative Irofulven-DRP ®

companion diagnostic to select and treat patients most likely to respond to the drug (study SMR-365).

This trial was not completed and

was an open-label, non-randomized, multi-center study in patients with docetaxel and AR-targeted therapy pre-treated mCRPC.

Up to 27 mCRPC

patients with predicted high probability of response to Irofulven (as determined by the Irofulven-DRP ® companion diagnostic)

were included.

A high likelihood of Irofulven response was defined as a patient having an Irofulven-DRP ® score of >80%.

The DNA binding

is primarily to the 3-N of deoxyadenosine (98%) with the remainder binding to 7-N deoxyguanine.

The resulting bulky single strand adducts

can cause single strand DNA breaks and S-phase double strand DNA breaks.

The GG-NER, BER and MMR pathways do not detect or remove Irofulven-DNA

adducts, which either persist into, or are created during, S-phase of cancer cell duplication and create double strand DNA breaks which

may be repaired by Homologous Recombination.

is more active in vitro against tumor cells of epithelial origin and is more resistant than other alkylating agents to deactivation

by p53 loss and MDR15.

Irofulven showed impressive anticancer results in xenograft models, shows synergy with topoisomerase I inhibitors,

and has demonstrated activity against cell lines that are resistant to other therapies.

Irofulven has significant scope for combination

with other therapies, including PARP inhibitors, checkpoint inhibitors (e.g.

PD-1 inhibitors) and standard chemotherapeutic regimes,

and is synergistic with other therapies targeting the TC-NER pathway and other DNA damage pathways.

causes apoptosis in sensitive tumor cell lines.

Activation of caspases 3, 7, 8, and 9 has been well documented in Irofulven-treated tumor

Irofulven also causes upregulation of ATM/Chk2 and ATR-dependent FANCD2 mono-ubiquitination.

In all cases, however, the functional

linkage(s) between irofulven adducts (both DNA and protein) and subsequent pathway activation steps are, at present, not fully understood.

DRP ® -Guided

Phase 2 Clinical Trial

to July 23, 2021, and our sale of Irofulven to Lantern Pharma, Inc., we commenced a DRP ® -guided Phase 2 clinical trial

of Irofulven in androgen receptor (AR)-targeted and Docetaxel-Pre-treated Metastatic Castration-Resistant Prostate Cancer (mCRPC) patients

using our putative Irofulven-DRP ® companion diagnostic to select and treat patients most likely to respond to the drug

(study SMR-365).

This trial was not completed and was an open-label, non-randomized, multi-center study in patients with docetaxel and

AR-targeted therapy pre-treated mCRPC.

Up to 27 mCRPC patients with predicted high probability of response to Irofulven (as determined

by the Irofulven-DRP ® companion diagnostic) were included.

A high likelihood of Irofulven response was defined as a patient

having an Irofulven-DRP ® score of >80%.

This study was suspended in 2019 when we internally deprioritized Irofulven.

We had previously developed and patented a putative DRP ®

companion diagnostic specific for Irofulven, which we believe enables us to identify and treat the patients most likely to respond to

this therapeutic candidate although we have not yet filed a PMA with the FDA for this companion diagnostic.

To devote more of our development

resources to our priority therapeutic candidates, on July 23, 2021, we terminated our drug development agreement for Irofulven and sold

our inventory of Irofulven active pharmaceutical ingredients, (“API”), our clinical data and records (“Data”),

and our know-how relating to Irofulven to Lantern Pharma, and granted a non-exclusive license to use our putative DRP ® companion

diagnostic specific for Irofulven.

Although we may be entitled to future milestone payments and royalties if Lantern Pharma advances the

development of Irofulven with or without our putative DRP ® companion diagnostic specific for Irofulven, we will no

longer devote any of our development resources to advance this therapeutic candidate.

Overview of Our PRP ® (Patient

Response Predictor)

Collections of drug specific

putative DRP ® companion diagnostics can be grouped together to form a panel of putative DRP ® companion diagnostics

that we believe can help guide therapeutic decision making for a given patient, in a true personalized medicine approach.

putative DRP ® companion diagnostics for a number of cancer drugs with a similar mechanism-of-action, for example chemotherapeutics

such as cisplatin, doxorubicin, and irofulven can be grouped together, by drug type (e.g.

DNA damaging agents) in a panel to help identify

which of these chemotherapeutics is most likely to benefit a particular patient.

Similarly, putative DRP ® companion diagnostics

for a number of cancer drugs with differing mechanism-of-action, such as fulvestrant, cisplatin, and dovitinib, can be grouped together,

by cancer type (e.g.

drugs that treat metastatic breast cancer) in a panel to help identify which of these drugs is most likely to benefit

a particular patient.

We call such panels of putative DRP ® companion diagnostics Patient Response Predictors (PRP ® s).

We believe PRP ® s,

once approved, have the potential to achieve the true promise of personalized cancer care, specifically to pre-screen a given cancer patient

for their likelihood of responding to a range of therapeutic options, then selecting the drug(s) most likely to benefit that patient,

while avoiding the prescription of therapeutics that are not likely to benefit that patient.

In practice, the treating oncologist and/or

cancer center would provide us with a tumor biopsy from a given patient (or gene expression data from such biopsy) and we would then run

a PRP ® analysis, as requested by the oncologist, resulting in a PRP ® report, provided to the oncologist

and the patient, identifying the therapy options most likely to benefit the patient.

This report would be somewhat analogous to currently

marketed predictive diagnostic panels and reports, such as FoundationOne ® (Foundation Medicine, Inc.), but with a different

underlying technology base and therapeutic response predictive power.

An example of such a PRP ®

product for multiple myeloma was published in 2018 where the sensitivity of 67 patients to 14 drugs was predicted.

We had previously developed and patented a putative DRP ® companion diagnostic specific for Irofulven, which we believe

enables us to identify and treat the patients most likely to respond to this therapeutic candidate although we have not yet filed a PMA

with the FDA for this companion diagnostic.

To devote more of our development resources to our priority therapeutic candidates, on July

23, 2021, we terminated our drug development agreement for Irofulven and sold our inventory of Irofulven active pharmaceutical ingredients,

(“API”), our clinical data and records (“Data”), and our know-how relating to Irofulven to Lantern Pharma, and

granted a non-exclusive license to use our putative DRP ® companion diagnostic specific for Irofulven.

may be entitled to future milestone payments and royalties if Lantern Pharma advances the development of Irofulven with or without our

putative DRP ® companion diagnostic specific for Irofulven, we will no longer devote any of our development resources

to advance this therapeutic candidate.

of Our PRP ® (Patient Response Predictor)

of drug specific putative DRP ® companion diagnostics can be grouped together to form a panel of putative DRP ®

companion diagnostics that we believe can help guide therapeutic decision making for a given patient, in a true personalized medicine

For example, putative DRP ® companion diagnostics for a number of cancer drugs with a similar mechanism-of-action,

for example chemotherapeutics such as cisplatin, doxorubicin, and irofulven can be grouped together, by drug type (e.g.

agents) in a panel to help identify which of these chemotherapeutics is most likely to benefit a particular patient.

Similarly, putative

DRP ® companion diagnostics for a number of cancer drugs with differing mechanism-of-action, such as fulvestrant, cisplatin,

and dovitinib, can be grouped together, by cancer type (e.g.

drugs that treat metastatic breast cancer) in a panel to help identify which

of these drugs is most likely to benefit a particular patient.

We call such panels of putative DRP ® companion diagnostics

Patient Response Predictors (PRP ® s).

believe PRP ® s, once approved, have the potential to achieve the true promise of personalized cancer care, specifically

to pre-screen a given cancer patient for their likelihood of responding to a range of therapeutic options, then selecting the drug(s)

most likely to benefit that patient, while avoiding the prescription of therapeutics that are not likely to benefit that patient.

practice, the treating oncologist and/or cancer center would provide us with a tumor biopsy from a given patient (or gene expression

data from such biopsy) and we would then run a PRP ® analysis, as requested by the oncologist, resulting in a PRP ®

report, provided to the oncologist and the patient, identifying the therapy options most likely to benefit the patient.

would be somewhat analogous to currently marketed predictive diagnostic panels and reports, such as FoundationOne ® (Foundation

Medicine, Inc.), but with a different underlying technology base and therapeutic response predictive power.

example of such a PRP ® product for multiple myeloma was published in 2018 where the sensitivity of 67 patients to

14 drugs was predicted.

Vangsted et al.

, Gene 644 80-86)

We continue to explore the

strategic and market potential of such PRP ® panels.

Market introduction and penetration of such personalized medicine diagnostic

tests and reports is challenging and subject to close scrutiny of regulatory agencies such as the FDA, and also are very capital intensive

to develop, bring to market, and expand sales.

Accordingly, development of a potential PRP ® product and business is not

currently part of our priority strategy.

Intellectual Property

Our commercial success depends

in large part on our ability to obtain and maintain patent protection in the U.S.

and other major oncology markets and countries for our

investigational products and our DRP ® companion diagnostics, to operate without being subject to the enforcement of third-party

patents and proprietary rights, and to prevent others from infringing on our proprietary or intellectual property rights.

We seek to protect

our proprietary position by (1) filing, in the U.S.

and certain other regions/countries (include the EU), patent applications intended

to cover our DRP ® companion diagnostics and their use with a particular therapeutic to guide patient therapy decision making,

and maintaining any DRP ® pending patent applications and issued patents in our major markets;

(2) maintaining and

advancing, and where possible expanding, existing patents and patent applications covering the composition-of-matter of our investigational

products, their methods of use and related discoveries, their formulations and methods of manufacture, and related technologies, inventions

and improvements that may be commercially important to our business;

and (3) filing, in the U.S.

and certain other regions/countries,

new patent applications on novel therapeutic uses of our investigational products, alone or together with their DRP ® companion

We may also rely on trade secrets and know-how to protect aspects of our business that are not amenable to, or that we do

not consider appropriate for, patent protection, and which are difficult to reverse engineer.

We also intend to take advantage of regulatory

protection afforded through data exclusivity, market exclusivity and patent term extensions where available.

have investigational products, and putative DRP ® companion diagnostics, for a number of therapeutic targets, although none

of our companion diagnostics have yet received FDA or other regulatory agency approval.

continue to explore the strategic and market potential of such PRP ® panels.

Market introduction and penetration of such

personalized medicine diagnostic tests and reports is challenging and subject to close scrutiny of regulatory agencies such as the FDA,

and also are very capital intensive to develop, bring to market, and expand sales.

Accordingly, development of a potential PRP ®

product and business is not currently part of our priority strategy.

commercial success depends in large part on our ability to obtain and maintain patent protection in the U.S.

and other major oncology

markets and countries for our investigational products and our DRP ® companion diagnostics, to operate without being subject

to the enforcement of third-party patents and proprietary rights, and to prevent others from infringing on our proprietary or intellectual

property rights.

We seek to protect our proprietary position by (1) filing, in the U.S.

and certain other regions/countries (include

the EU), patent applications intended to cover our DRP ® companion diagnostics and their use with a particular therapeutic

to guide patient therapy decision making, and maintaining any DRP ® pending patent applications and issued patents in our

major markets;

(2) maintaining and advancing, and where possible expanding, existing patents and patent applications covering the

composition-of-matter of our investigational products, their methods of use and related discoveries, their formulations and methods of

manufacture, and related technologies, inventions and improvements that may be commercially important to our business;

and (3) filing,

and certain other regions/countries, new patent applications on novel therapeutic uses of our investigational products, alone

or together with their DRP ® companion diagnostics.

We may also rely on trade secrets and know-how to protect aspects of

our business that are not amenable to, or that we do not consider appropriate for, patent protection, and which are difficult to reverse

We also intend to take advantage of regulatory protection afforded through data exclusivity, market exclusivity and patent

term extensions where available.

have investigational products, and putative DRP ® companion diagnostics, for a number of therapeutic targets, although

none of our companion diagnostics have yet received FDA or other regulatory agency approval.

As of the date of this report, our Company-owned

patent portfolio consists of:

17 DRP ® companion diagnostics patents granted covering 70 different cancer drugs, including 8 issued patents in the U.S.

DRP ® companion diagnostics patents granted covering 70 different cancer drugs,

including 8 issued patents in the U.S.

and 4 issued patents in the EU.

Our issued patents cover, among others, DRP ® companion diagnostics for Dovitinib, LiPlaCis ® , 2X-111, and Irofulven.

Our issued patent portfolio includes patents granted in the U.S., EU, China, Japan, Canada, and Australia.

27 DRP ® companion diagnostics patent applications pending covering 2 additional drugs, including pending applications in the U.S., EU, China, Japan, Canada, India, Brazil and Australia.

Our pending patent applications cover, among others, DRP ® companion diagnostics for IXEMPRA ® and for Stenoparib.

Over 50 granted patents and pending patent applications, for composition-of-matter, methods of use, formulation, and methods of manufacturing, for many of our pipeline assets, including Dovitinib, Stenoparib, and 2X-111.

These granted patents and applications generally cover the U.S.

Our issued patents

cover, among others, DRP ® companion diagnostics for Dovitinib, LiPlaCis ® ,

2X-111, and Irofulven.

Our issued patent portfolio includes patents granted in the U.S.,

EU, China, Japan, Canada, and Australia.

DRP ® companion diagnostics patent applications pending covering 2 additional

drugs, including pending applications in the U.S., EU, China, Japan, Canada, India, Brazil

and Australia.

Our pending patent applications cover, among others, DRP ® companion

diagnostics for IXEMPRA ® and for Stenoparib.

50 granted patents and pending patent applications, for composition-of-matter, methods of

use, formulation, and methods of manufacturing, for many of our pipeline assets, including

Dovitinib, Stenoparib, and 2X-111.

These granted patents and applications generally cover

and EU, as well as numerous additional major world cancer therapeutics markets;

although existing and remaining patent/application coverage varies from drug program to drug program.

In some instances, we own and control such pre-existing patent/application portfolios (such as for Dovitinib) and in some instances the original drug owner/licensor owns and controls such pre-existing patent/application portfolios (such as for Stenoparib).

patent application pending covering novel anti-viral uses of Stenoparib as a therapeutic for treatment of COVID-19 infection.

The term of any patents that issue from our company-owned (or in-licensed) U.S.

and foreign patent applications will vary in accordance with the laws of each jurisdiction and available patent term extension but is typically 20 years from the earliest priority application filing date.

Expiration dates for certain patents covering our portfolio assets ranges between 2028 and 2032.

Expiration dates for the DRP ® companion diagnostic patents that cover our current pipeline programs will typically expire between 2030 and 2040.

Any patents that may issue in the future from our company-owned (or in-licensed) pending patent applications are projected to expire between 2031 and 2041, unless extended or otherwise adjusted.

Generally, the older and more developed the drug program the earlier the patent portfolio on the product will expire.

For example, remaining patent portfolio term for dovitinib is less than remaining patent term for stenoparib.

Such product patent portfolio expiration is independent from continuing patent coverage provided by DRP ® companion diagnostics for each product.

In countries or regions, such as the U.S.

and EU, where regulatory approval of a companion diagnostic together with its drug, on the label, is available, approved DRP ® companion diagnostics will substantially extend patent protection well after the core product patents (e.g.

although existing and remaining patent/application coverage varies from drug program to drug

The dovitinib patent portfolio is being returned to Novartis.

In some instances

the original drug owner/licensor owns and controls such pre-existing patent/application portfolios

(such as for Stenoparib).

patent application pending covering novel anti-viral uses of Stenoparib as a therapeutic

for treatment of COVID-19 infection.

term of any patents that issue from our company-owned (or in-licensed) U.S.

and foreign patent

applications will vary in accordance with the laws of each jurisdiction and available patent

term extension but is typically 20 years from the earliest priority application filing

Expiration dates for certain patents covering our portfolio assets ranges between 2028

Expiration dates for the DRP ® companion diagnostic patents that

cover our current pipeline programs will typically expire between 2030 and 2040.

that may issue in the future from our company-owned (or in-licensed) pending patent applications

are projected to expire between 2031 and 2041, unless extended or otherwise adjusted.

the older and more developed the drug program the earlier the patent portfolio on the product

For example, remaining patent portfolio term for dovitinib is less than remaining

patent term for stenoparib.

Such product patent portfolio expiration is independent from

continuing patent coverage provided by DRP ® companion diagnostics for each

countries or regions, such as the U.S.

and EU, where regulatory approval of a companion diagnostic

together with its drug, on the label, is available, approved DRP ® companion

diagnostics will substantially extend patent protection well after the core product patents

composition-of-matter) have expired.

We have obtained or are pursuing

patent protection for our proprietary drug response predictor (DRP ® ) technology, a unique diagnostic platform, with a particular

focus on the application of the DRP ® technology to treat renal cell carcinoma, ovarian cancer, and metastatic breast cancer.

Specifically, the DRP ® technology is being applied to select patients to be treated with dovitinib, stenoparib, or ixabepilone.

Our patent portfolio also includes patents and applications in-licensed from Novartis International AG (“Novartis”) that protect

dovitinib compositions and methods of its use for treatment, as well as patents and applications in-licensed from Eisai Co., Ltd.

that protect stenoparib compositions and methods of its use for treatment.

Our in-licensed patent on the composition of matter for dovitinib

expired on September 11, 2021.

Our dovitinib patent portfolio,

which includes U.S.

and foreign patents and patent applications, is positioned to protect aspects of our business in the United States

and in key foreign jurisdictions.

The following is a brief summary of the dovitinib patent portfolio, which includes in-licensed patent

families, as well as patent families owned by us.

In-licensed patents:

Patents granted in the United States (US 9,545,402), Australia (AU 2011273519), Canada (CA 2,801,826), China (CN 106943355), Europe (EP 2588086), and Japan (JP 2013-517282) from national stage applications of Patent Cooperation Treaty Application No.

PCT/EP2011/060949, protect pharmaceutical dovitinib compositions and methods for producing pharmaceutical compositions containing dovitinib.

The patents are scheduled to expire beginning in 2031.

Patents granted in the United States (US 8,741,903), Europe (EP 2558095), and Australia (AU 2011239999) from national stage applications of Patent Cooperation Treaty Application No.

PCT/EP2011/055906, protect methods of treating hepatocellular carcinoma or liver cancer with dovitinib.

The patents are scheduled to expire beginning in 2031.

Owned patents:

We have patent rights covering the use of the DRP ® technology in conjunction with dovitinib in the United States (US 10,835,531).

Patent rights outside the U.S.

are being pursued in key foreign jurisdictions, including Australia, Canada, China, Europe, India, and Japan as national stage applications of Patent Cooperation Treaty Application No.

PCT/EP2020/066724 filed in November 2021.

This portfolio is scheduled to expire in 2040.

Our stenoparib patent portfolio,

which includes U.S.

and foreign patents and patent applications, is positioned to protect aspects of our business in the United States

and in key foreign jurisdictions.

The following is a brief summary of the stenoparib patent portfolio, which includes patent families

in-licensed from Eisai, as well as patent applications owned by Allarity.

In-licensed patents:

Patents granted from national stage applications of Patent Cooperation Treaty Application No.

PCT/US2008/078606 that are in-licensed from Eisai include composition of matter claims directed to genera and species encompassing stenoparib.

Patents have issued in the United States (US 8,236,802 and US 8,894,989) and in key foreign jurisdictions including, e.g., Europe (EP 2209375), Canada (CA 2,700,903), China (CN 102083314B), Japan (JP 5439380), and South Korea (KR 10-1596526).

have obtained or are pursuing patent protection for our proprietary DRP ® technology, a unique diagnostic platform, with

a particular focus on the application of the DRP ® technology to treat renal cell carcinoma, ovarian cancer, and metastatic

breast cancer.

Specifically, the DRP ® technology is being applied to select patients to be treated with dovitinib, stenoparib,

or ixabepilone.

Our patent portfolio includes patents and applications in-licensed from Eisai Co., Ltd.

(“Eisai”) that protect

stenoparib compositions and methods of its use for treatment.

– Terminated program

interest in Dovitinib has been terminated as has the agreement with Novartis.

Therefore, there will be no more dovitinib development

stenoparib patent portfolio, which includes U.S.

and foreign patents and patent applications, is positioned to protect aspects of our

business in the United States and in key foreign jurisdictions.

The following is a brief summary of the stenoparib patent portfolio,

which includes patent families in-licensed from Eisai, as well as patent applications owned by Allarity.

granted from national stage applications of Patent Cooperation Treaty Application No.

PCT/US2008/078606

that are in-licensed from Eisai include composition of matter claims directed to genera and

species encompassing stenoparib.

Patents have issued in the United States (US 8,236,802 and

US 8,894,989) and in key foreign jurisdictions including, e.g., Europe (EP 2209375), Canada

(CA 2,700,903), China (CN 102083314B), Japan (JP 5439380), and South Korea (KR 10-1596526).

The patents are scheduled to expire in 2028.

Owned patents:

We are pursuing patent protection for the use of our DRP ® technology in conjunction with stenoparib via national stage applications of Patent Cooperation Treaty Application No.

PCT/EP2019/062508 filed in the United States, Australia, Canada, China, Europe, India, and Japan.

are pursuing patent protection for the use of our DRP ® technology in conjunction

with stenoparib via national stage applications of Patent Cooperation Treaty Application

PCT/EP2019/062508 filed in the United States, Australia, Canada, China, Europe, India,

This portfolio is scheduled to expire in 2039.

Our ixabepilone patent portfolio,

which is owned by us, is based on protecting our DRP ® technology in the United States and in key foreign jurisdictions.

ixabepilone patent portfolio, which is owned by us, is based on protecting our DRP ® technology in the United States and

in key foreign jurisdictions.

We have filed national stage applications of Patent Cooperation Treaty Application No.

PCT/EP2021/052132, which seeks to cover the use

of the DRP ® technology in conjunction with ixabepilone, in the United States and in key foreign jurisdictions, including

Australia, Canada, China, Europe, India, and Japan starting in July 2022.

This portfolio is scheduled to expire in 2041.

We do not own

or control any patents relating to ixabepilone itself in the EU market, where such patents have previously expired.

Our 2X-111 patent portfolio,

which includes U.S.

and foreign patents and patent applications, is positioned to protect aspects of our business in the United States

and in key foreign jurisdictions.

The following is a brief summary of the 2X-111 patent portfolio, which includes patent families in-licensed

from 2BBB Medicines, B.V., as well as patent and patent applications owned by Allarity.

In-licensed patents:

Our 2X-111 patent portfolio

includes the following patent families in-licensed from 2BBB Medicines, B.V.:

(1) drug conjugates, which patents are issued and in force

until March 2028;

(2) liposomal delivery system, which patents are issued and in force until December 2025;

and modified drug delivery

system, which patents are issued and in force until February 2030.

Generally, the issued patents of each patent family cover most of the

European Union countries, including, among others, Germany, Spain, United Kingdom, Italy, France, and Turkey.

Patents within family (3)

have also been granted in Australia, Canada, China, Japan and New Zealand.

Owned patents:

We own exclusive, global rights

to the use of our DRP ® technology in conjunction with doxorubicin, which is the active therapeutic ingredient of 2X-111.

PCT/EP2021/052132,

which seeks to cover the use of the DRP ® technology in conjunction with ixabepilone, in the United States and in key foreign

jurisdictions, including Australia, Canada, China, Europe, India, and Japan starting in July 2022.

This portfolio is scheduled to expire

We do not own or control any patents relating to ixabepilone itself in the EU market, where such patents have previously expired.

own exclusive, global rights to the use of our DRP ® technology in conjunction with doxorubicin, which is the active therapeutic

ingredient of 2X-111.

A patent to this technology has issued in the United States (US 10,900,089) and Europe (EP18172585.4).

Patent applications are also pending

in Australia, Canada, China, Hong Kong, and India.

Patent applications

are also pending in Australia, Canada, China, Hong Kong, and India.

This portfolio is scheduled to expire in 2038.

The patent positions for biotechnology

and pharmaceutical companies like us are generally uncertain and can involve complex legal, scientific and factual issues.

either the patent laws or their interpretation in the U.S.

and other countries may diminish our ability to protect our investigational

products and/or DRP ® companion diagnostics and enforce the patent rights that we own or to which we have exclusive rights,

and could affect the value of such intellectual property and the business.

See section entitled “Risk Factors - Risks Related to

Our Intellectual Property” for list of risks related to our intellectual property.

License Agreement with Novartis Pharma for

On April 6, 2018, Allarity

Therapeutics Europe ApS (“Allarity Europe”), our wholly owned subsidiary, in-licensed the exclusive worldwide rights to all

therapeutic and/or diagnostic uses related to cancer in humans for dovitinib from Novartis Pharma AG (“Novartis”) pursuant

to a license agreement.

Upon execution of the agreement, Allarity Europe paid Novartis a one-time, non-refundable, non-creditable upfront

payment of $1 million.

Pursuant to the agreement, we are solely responsible for the development of dovitinib during the term of the agreement.

The agreement also contemplated that a convertible promissory note in the amount of $1 million would also be issued to Novartis by one

of our subsidiaries but was unenforceable due to the operation of the liability limitation provisions of the license agreement.

of current discussions with Novartis over the possible restructuring of the milestone payments described below, the parties entered into

an amendment to the license agreement on April 12, 2022, to be effective as of March 30, 2022, to exclude the convertible promissory note

from the liability limitation provisions of the license agreement and, subject to the parties execution of the amendment to the license

agreement, our subsidiary executed an enforceable convertible promissory note in the principal amount of $1 million with a maturity date

of April 6, 2025 (the “Novartis Promissory Note”).

The Novartis Promissory Note will bear interest at the rate of 5% per annum

commencing on April 6, 2018, which shall be paid, together with the principal amount, on the maturity date.

The Novartis Promissory Note

was issued by Allarity Therapeutics Denmark ApS (“Allarity Denmark”), a wholly owned special purpose vehicle of our subsidiary

Allarity Europe, the licensee under the license agreement.

In the event that there is a change of control, as defined under the Novartis

Promissory Note, of Allarity Europe, Novartis would be entitled to a payment equal to 5% of the first $30 million we receive in connection

with the change of control and up to 3% of any amounts we receive in excess of $30 million in connection with the change of control.

addition, in the event Allarity Denmark undertakes an initial public offering (“IPO”) resulting in its shares being listed

on an internationally recognized securities exchange, then Novartis would have a one-time right to convert all amounts owed under the

Novartis Promissory Note into 3% of Allarity Denmark outstanding equity securities immediately before the IPO.

Development Milestone Payments

Pursuant to the agreement,

as amended on September 27, 2022, Allarity Europe has agreed to make milestone payments to Novartis in connection with the development

of dovitinib by us or our affiliates, or by a third-party (a “Program Acquirer”) that assumes control of the dovitinib development

program from us corresponding to:

(i) upon enrollment of half of the patients required in a Phase 2 clinical trials in certain countries

in accordance with agreed upon protocols;

(ii) upon dosing of the first patient in the first Phase 3 clinical trial;

submission of the first NDA with the FDA;

(iv) submission of a first application or submission for approval to market a pharmaceutical

product (“MAA”) to the EMA or any other Regulatory Authority in certain countries;

(v) upon receipt of the first authorization

by the FDA to market and sell a licensed product;

and (vi) upon receipt of a first MAA (including a respective pricing and reimbursement

approval) for a licensed product in one or more specified European countries.

If all milestones have been achieved, we may be obligated

to pay Novartis up to a maximum of $26.5 million.

As of December 31, 2021, prior to the September 27, 2022, amendment, we accrued a $5

million royalty payment due to Novartis as a current liability relating to the submission of our NDA to the FDA for the treatment of mRCC.

The September 27, 2022, amendment restructured the payment terms of this milestone payment into an installment plan with the final installment

due in 2023, allowing us more time to make the milestone payment in exchange for a $500,000 increase in the amount of the milestone payment.

In the event that we complete a Financing Transaction, as defined in the amendment, the installment payments would be accelerated.

Royalty Payments

In addition to the milestone

payments described above, Allarity Europe has agreed to pay Novartis royalties based on annual incremental sales of product derived from

dovitinib in an amount between 5% and 10% of annual sales of between $0 and $250 million, between 6% and 13% of annual sales between $250

million and $500 million, between 7% and 13% of annual sales between $500 million and $750 million, and between 13% and 15% of annual

sales in excess of $750 million.

Allarity Europe is are obligated

to pay royalties under the agreement on a country-by-country and product-by-product basis for a period that commences with the first commercial

sale of a product until the later of (i) the expiration of the last to expire valid claim of any licensed patent covering such licensed

product in such country;

or, (ii) the expiration of regulatory-based exclusivity for such licensed product in such country or (iii) the

10 year anniversary of the date of first commercial sale of such licensed product in such country.

However, the agreement may be sooner

terminated without cause by Allarity Europe upon 120 days prior written notice, or upon written notice of a material breach of the

agreement by Novartis that is not cured within 30 days.

Novartis also has the right to terminate the agreement upon written notice

of a material breach of the agreement by us that is not cured within 30 days or if we file for bankruptcy.

License Agreement with Eisai for Stenoparib

On July 6, 2017, we in-licensed

the exclusive worldwide rights to all preventative, therapeutic and/or diagnostic uses related to cancer in humans and by amendment to

the agreement on December 11, 2020, viral infections in humans (including, but not limited to, coronavirus vaccines and other treatments)

for stenoparib from Eisai Inc.

patent positions for biotechnology and pharmaceutical companies like us are generally uncertain and can involve complex legal, scientific

and factual issues.

Changes in either the patent laws or their interpretation in the U.S.

and other countries may diminish our ability

to protect our investigational products and/or DRP ® companion diagnostics and enforce the patent rights that we own or

to which we have exclusive rights, and could affect the value of such intellectual property and the business.

See section entitled “Risk

Factors - Risks Related to Our Intellectual Property” for list of risks related to our intellectual property.

Agreement with Novartis Pharma for Dovitinib

agreement was terminated by Novartis effective January 26, 2024.

Agreement with Eisai for Stenoparib

July 6, 2017, we in-licensed the exclusive worldwide rights to all preventative, therapeutic and/or diagnostic uses related to cancer

in humans and by amendment to the agreement on December 11, 2020, viral infections in humans (including, but not limited to, coronavirus

vaccines and other treatments) for stenoparib from Eisai Inc.

(“Eisai”) pursuant to a license agreement.

Upon the execution of the agreement in 2017, we

paid Eisai a one-time, non-refundable, and non-creditable payment of $1 million.

Pursuant to the license agreement, we are solely responsible

for the development of stenoparib during the term of the agreement.

The agreement also provides for a joint development committee consisting

of six members, three appointed by us and three appointed by Eisai.

One of our members of the joint development committee is designated

chair of the committee and has the power to break any deadlock in decisions by the committee that must be made by a majority vote with

each representative having one vote.

The purpose of the committee is to implement and oversee development activities for stenoparib pursuant

to the clinical development plan and serve as a forum for exchanging data, information, and development strategy.

Development Milestone Payments

Pursuant to the agreement,

we have agreed to make milestone payments to Eisai in connection with the development of stenoparib by us or our affiliates, or by a third-party

(a “Program Acquirer”) that assumes control of the stenoparib development program from us corresponding to:

(i) successful

completion of a Phase 2 clinical trial;

Upon the execution

of the agreement in 2017, we paid Eisai a one-time, non-refundable, and non-creditable payment of $1 million.

Pursuant to the license

agreement, we are solely responsible for the development of stenoparib during the term of the agreement.

The agreement also provides

for a joint development committee consisting of six members, three appointed by us and three appointed by Eisai.

One of our members of

the joint development committee is designated chair of the committee and has the power to break any deadlock in decisions by the committee

that must be made by a majority vote with each representative having one vote.

The purpose of the committee is to implement and oversee

development activities for stenoparib pursuant to the clinical development plan and serve as a forum for exchanging data, information,

and development strategy.

Milestone Payments

to the agreement, we have agreed to make milestone payments to Eisai in connection with the development of stenoparib by us or our affiliates,

or by a third-party (a “Program Acquirer”) that assumes control of the stenoparib development program from us corresponding

(i) successful completion of a Phase 2 clinical trial;

(ii) dosing of the first patient in the first Phase 3 clinical trial;

(iii) submission of

the first NDA with the FDA;

(iii) submission of the first NDA with the FDA;

(iv) submission of an MAA to the EMA;

(v) submission of an NDA to the Ministry of Health Labor and

Welfare of Japan, or the Pharmaceuticals and Medical Devices Agency of Japan, or any successor thereto (the “MHLW”);

of authorization by the FDA to market and sell a licensed product;

(vii) receipt of approval of an MAA by the EMA for a licensed

(v) submission of an NDA to the

Ministry of Health Labor and Welfare of Japan, or the Pharmaceuticals and Medical Devices Agency of Japan, or any successor thereto (the

(vi) receipt of authorization by the FDA to market and sell a licensed product;

(vii) receipt of approval

of an MAA by the EMA for a licensed product;

and (viii) receipt of approval by the MHLW in Japan for a licensed product.

If all milestones have been achieved, we may

be obligated to pay Eisai up to a maximum of $94 million.

In addition, we have agreed to pay Eisai a one-time sales milestone payment

in the amount of $50 million the first time our annual sales of licensed product are $1 billion or more.

Royalty Payments

In addition to the milestone

payments described above, we have agreed to pay Eisai royalties based on annual incremental sales of product derived from stenoparib in

an amount between 5% and 10% of annual sales of between $0 and $100 million, between 6% and 10% of annual sales between $100 million and

$250 million, between 7% and 11% of annual sales between $250 million and $500 million, and between 11% and 15% of annual sales in excess

of $500 million.

We are obligated to pay royalties

under the agreement on a country-by-country and product-by-product basis for a period that commences with the first commercial sale of

a product until the later of (i) the expiration of the last to expire valid claim of any licensed patent covering such licensed product

in such country;

or, (ii) the expiration of regulatory-based exclusivity for such licensed product in such country or (iii) the

15 year anniversary of the date of first commercial sale of such licensed product in such country.

However, the agreement may be sooner

terminated without cause by us upon 120 days prior written notice, or upon written notice of a material breach of the agreement by

Eisai that is not cured within 90 days (30 days for a payment default).

Eisai also has the right to terminate the agreement

upon written notice of a material breach of the agreement by us that is not cured within 90 days (30 days for a payment default)

or if we file for bankruptcy.

By an amendment effective as of August 3, 2021, and executed by Eisai on August 23, 2021, Eisai also had

the right to terminate the agreement if we did not complete a Phase 2 clinical trial before December 31, 2022, unless we elected

to pay a $1 million extension payment (“Extension Payment”).

Notwithstanding the foregoing, in the event we failed to enroll

and dose at least 30 patients with the first dose of cancer drug in the ongoing Phase 2 Ovarian Cancer Clinical Trial by July 1, 2022,

then the Extension Payment would have become due and payable in full on July 30, 2022.

By a further amendment effective July 12, 2022,

and executed by Eisai on August 17, 2022, in exchange for a payment of $100,000 on or before August 27, 2022, and a further $900,000 payment

on or before April 1, 2023, which will constitute the payment of the Extension Payment, we will have until April 1, 2024, to complete

a Phase 1b or Phase 2 Clinical Trial.

We have paid the initial $100,000 of the Extension Payment and have until April 1, 2023, to pay

the remaining $900,000.

Consequently, if we fail to pay the remaining $900,000 of the Extension Payment on or before April 1, 2023, or

if we fail to achieve successful completion of a Phase 1b or Phase 2 Clinical Trial prior to April 1, 2024, then Eisai may terminate the

agreement in its sole discretion pursuant to the terms of the amendment.

Option to Reacquire Rights to Stenoparib

For the period of time commencing

with enrollment of the first five patients in a Phase 2 clinical trial pursuant to the clinical development plan and ending 90 days following

successful completion of such Phase 2 clinical trial, Eisai has the option to reacquire our licensed rights to develop stenoparib

for a purchase price equal to the fair market value of our rights, giving effect to the stage of development of stenoparib that we have

completed under the agreement.

We commenced a Phase 2 clinical trial in April 2019 and as of the date of this report, Eisai has not indicated

an intention to exercise its repurchase option.

Sub-License Agreements with OncoHeroes Biosciences

for Dovitinib & Stenoparib

On January 2, 2022, we sub-licensed

the exclusive worldwide rights to any and all pediatric cancer development and commercialization of dovitinib and stenoparib to OncoHeroes

Biosciences, Inc.

Upon the execution of the agreements, OncoHeroes paid us a one-time, non-refundable, and non-creditable payment of $350,000.

Pursuant to the license agreements, OncoHeroes is solely responsible for the pediatric cancer development of stenoparib and dovitinib,

together with their respective DRP ® companion diagnostics, during the term of the agreements.

The agreements also provide

for a joint development committee consisting of five members, three appointed by OncoHeroes and two appointed by us.

The purpose of the

committee is to implement and oversee pediatric cancer development activities for stenoparib and dovitinib pursuant to the clinical development

plan and serve as a forum for exchanging data, information, and development strategy.

Under the agreements, Allarity will provide, at

its own cost, DRP ® companion diagnostic support for any pediatric clinical trials that OncoHeroes conducts in Europe;

pediatric clinical trials, Allarity will facilitate DRP ® companion diagnostic support through its U.S.

partner, Almac, at OncoHeroes’ cost.

Further, under the Agreements, Allarity shall supply finished stenoparib and dovitinib to OncoHeroes

at our cost of goods (to manufacture or have manufactured the drugs).

In certain events where Allarity is unwilling or unable to supply

sufficient amounts of the drugs, OncoHeroes can obtain manufacturing rights from Allarity.

Development Milestone Payments

Pursuant to the agreements,

OncoHeroes will make milestone payments to us in connection with its development of stenoparib and dovitinib, or by a third-party (a “Program

Acquirer”) that assumes control of the development programs from OncoHeroes, corresponding to, for each drug:

(i) upon receipt of

authorization by the FDA to market and sell a licensed product;

and (ii) upon receipt of approval of an MAA by the EMA for a licensed

Royalty Payments

In addition to the milestone

payments described above, OncoHeroes has agreed to pay us royalties based on annual incremental sales of any product derived from stenoparib

and/or dovitinib in an amount between 5% and 8% of annual sales of between $0 and $100 million, between 9% and 11% of annual sales between

$100 million and $200 million, and between 11% and 14% of annual sales above $200 million.

OncoHeroes is obligated to

pay us royalties under the agreements on a country-by-country and product-by-product basis for a period that commences with the first

commercial sale of a product until the later of (i) the expiration of the last to expire valid claim of any licensed patent covering

such licensed product in such country;

or, (ii) the 10 year anniversary of the date of first commercial sale of dovitinib in such

country and the 15 year anniversary of the date of first commercial sale of stenoparib in such country.

However, the agreements may be

sooner terminated upon written notice of Allarity of a material breach of the agreements by OncoHeroes that is not cured within 60 days.

After the first anniversary of each agreement, OncoHeroes also has the right to terminate the agreements, at will, upon written notice

to Allarity (i) 90 days in advance if prior to first commercial sale of license product or (ii) 180 days in advance if after first commercial

sale of licensed product.

Option to Reacquire Rights

Under the terms of the agreements,

Allarity has a first buy back option for licensed pediatric cancer field rights for each of stenoparib and dovitinib triggered by the

first to occur of (i) written notice from Allarity to OncoHeroes that it has received an offer from a pharmaceutical company with at least

$250 million of net sales (based upon its most recently-completed calendar year financial performance) that wishes to acquire global commercialization

rights to the product in the licensed field (pediatric cancers) and retained field (all other cancers);

or (ii) completion of the receipt

of the first MAA (including an NDA) approval for a product in any country in the licensed territory (worldwide) in the licensed field;

milestones have been achieved, we may be obligated to pay Eisai up to a maximum of $94 million.

In addition, we have agreed to pay Eisai

a one-time sales milestone payment in the amount of $50 million the first time our annual sales of licensed product are $1 billion or

addition to the milestone payments described above, we have agreed to pay Eisai royalties based on annual incremental sales of product

derived from stenoparib in an amount between 5% and 10% of annual sales of between $0 and $100 million, between 6% and 10% of annual

sales between $100 million and $250 million, between 7% and 11% of annual sales between $250 million and $500 million, and between 11%

and 15% of annual sales in excess of $500 million.

We are obligated to pay royalties under the agreement on a country-by-country

and product-by-product basis for a period that commences with the first commercial sale of a product until the later of (i) the expiration

of the last to expire valid claim of any licensed patent covering such licensed product in such country;

or, (ii) the expiration

of regulatory-based exclusivity for such licensed product in such country or (iii) the 15 year anniversary of the date of first commercial

sale of such licensed product in such country.

However, the agreement may be sooner terminated without cause by us upon 120 days

prior written notice, or upon written notice of a material breach of the agreement by Eisai that is not cured within 90 days (30 days

for a payment default).

Eisai also has the right to terminate the agreement upon written notice of a material breach of the agreement

by us that is not cured within 90 days (30 days for a payment default) or if we file for bankruptcy.

By an amendment effective

as of August 3, 2021, and executed by Eisai on August 23, 2021, Eisai also had the right to terminate the agreement if we did not complete

a Phase 2 clinical trial before December 31, 2022, unless we elected to pay a $1 million extension payment (“Extension Payment”).

Notwithstanding the foregoing, in the event we failed to enroll and dose at least 30 patients with the first dose of cancer drug in the

ongoing Phase 2 Ovarian Cancer Clinical Trial by July 1, 2022, then the Extension Payment would have become due and payable in full on

July 30, 2022.

By a further amendment effective July 12, 2022, and executed by Eisai on August 17, 2022, in exchange for a payment of

$100,000 on or before August 27, 2022, and a further $900,000 payment on or before April 1, 2023, which will constitute the payment of

the Extension Payment, we will have until April 1, 2024, to complete a Phase 1b or Phase 2 Clinical Trial.

On May 26, 2023, the Company and Eisai entered into a fourth amendment

to the Exclusive License Agreement with an effective date of May 16, 2023, to postpone the extension payment, restructure the payment

schedule and extend the deadline to complete enrollment in a further Phase 1b or Phase 2 Clinical Trial for the Stenoparib (the “Product”).

The Company agreed to pay Eisai in periodic payments as follows:

(i) $100 which has been paid;

(ii) $50 within 10 days of execution of

the fourth amendment which has been paid;

(iii) $100 upon completion of a capital raise (paid on July 18, 2023);

and (iv) $850 on or before

March 1, 2024.

As of the date of this filing, the Company is currently negotiating a fifth amendment to the extend the timeframe of periodic

payments due.

to Reacquire Rights to Stenoparib

the period of time commencing with enrollment of the first five patients in a Phase 2 clinical trial pursuant to the clinical development

plan and ending 90 days following completion of a successful Phase 2 trial (greater than or equal to 20% ORR by RECIST criteria), , Eisai

has the option to reacquire our licensed rights to develop stenoparib for a purchase price equal to the fair market value of our rights,

giving effect to the stage of development of stenoparib that we have completed under the agreement.

We commenced a Phase 2 clinical trial

in April 2019 and as of the date of this report, Eisai has not indicated an intention to exercise its repurchase option.

Agreements with OncoHeroes Biosciences for Dovitinib & Stenoparib

agreements with Oncoheroes are currently being re-evaluated by new leadership at Allarity.

The sections below are retained for reference.

January 2, 2022, we sub-licensed the exclusive worldwide rights to any and all pediatric cancer development and commercialization of

dovitinib and stenoparib to OncoHeroes Biosciences, Inc.

Upon the execution of the agreements, OncoHeroes paid us a one-time, non-refundable,

and non-creditable payment of $350,000.

Pursuant to the license agreements, OncoHeroes is solely responsible for the pediatric cancer

development of stenoparib and dovitinib, together with their respective DRP ® companion diagnostics, during the term of

the agreements.

The agreements also provide for a joint development committee consisting of five members, three appointed by OncoHeroes

and two appointed by us.

The purpose of the committee is to implement and oversee pediatric cancer development activities for stenoparib

and dovitinib pursuant to the clinical development plan and serve as a forum for exchanging data, information, and development strategy.

Under the agreements, Allarity will provide, at its own cost, DRP ® companion diagnostic support for any pediatric clinical

trials that OncoHeroes conducts in Europe;

pediatric clinical trials, Allarity will facilitate DRP ® companion

diagnostic support through its U.S.

CLIA lab partner, Almac, at OncoHeroes’ cost.

Further, under the Agreements, Allarity shall

supply finished stenoparib and dovitinib to OncoHeroes at our cost of goods (to manufacture or have manufactured the drugs).

events where Allarity is unwilling or unable to supply sufficient amounts of the drugs, OncoHeroes can obtain manufacturing rights from

Allarity has notified OncoHeroes that its license to dovitinib has been terminated by Novartis.

Milestone Payments

to the agreements, OncoHeroes will make milestone payments to us in connection with its development of stenoparib and dovitinib, or by

a third-party (a “Program Acquirer”) that assumes control of the development programs from OncoHeroes, corresponding to,

for each drug:

(i) upon receipt of authorization by the FDA to market and sell a licensed product;

and (ii) upon receipt of approval

of an MAA by the EMA for a licensed product.

As noted above, because our agreement with Novartis has been terminated, our agreement with

OncoHeroes may be subject to revision in the near future.

addition to the milestone payments described above, OncoHeroes has agreed to pay us royalties based on annual incremental sales of any

product derived from stenoparib in an amount between 5% and 8% of annual sales of between $0 and $100 million, between 9% and 11% of

annual sales between $100 million and $200 million, and between 11% and 14% of annual sales above $200 million.

is obligated to pay us royalties under the agreements on a country-by-country and product-by-product basis for a period that commences

with the first commercial sale of a product until the later of (i) the expiration of the last to expire valid claim of any licensed

patent covering such licensed product in such country;

or, (ii) the 15 year anniversary of the date of first commercial sale of

stenoparib in such country.

However, the agreements may be sooner terminated upon written notice of Allarity of a material breach of

the agreements by OncoHeroes that is not cured within 60 days.

After the first anniversary of each agreement, OncoHeroes also has

the right to terminate the agreements, at will, upon written notice to Allarity (i) 90 days in advance if prior to first commercial sale

of license product or (ii) 180 days in advance if after first commercial sale of licensed product.

to Reacquire Rights

the terms of the agreements, Allarity has a first buy back option for licensed pediatric cancer field rights for each of stenoparib triggered

by the first to occur of (i) written notice from Allarity to OncoHeroes that it has received an offer from a pharmaceutical company with

at least $250 million of net sales (based upon its most recently-completed calendar year financial performance) that wishes to acquire

global commercialization rights to the product in the licensed field (pediatric cancers) and retained field (all other cancers);

completion of the receipt of the first MAA (including an NDA) approval for a product in any country in the licensed territory (worldwide)

in the licensed field;

and (b) ending 120 days after the occurrence of the matters set forth in clause (i) and (ii) above, as applicable.

Allarity may exercise

its buy back option by submitting a written offer prior to the expiration of the option period outlined above.

Upon the timely exercise

by Allarity of its option:

(i) any development milestone payments due from OncoHeroes to Allarity shall be cancelled, and (ii) the parties

shall enter into exclusive good faith negotiations regarding a fair market value (“FMV”) payment to OncoHeroes which will

take into account the value generated by OncoHeroes to the product, and may include a one-off payment to OncoHeroes and royalties on future

net sales for the product, or a one-time upfront payment, or such other FMV as the parties shall negotiate in good faith.

Development, Option and License Agreement with

R-Pharm for IXEMPRA ®

On March 1, 2019, we entered

into an option to in-license the rights to any and all therapeutic and/or diagnostic uses in humans for IXEMPRA ®

in the European Union (including Great Britain but excluding Switzerland and Lichtenstein) (the “Territory”) from R-Pharm

Allarity may exercise its buy back option by submitting a written offer prior to the expiration of the option period outlined above.

Upon the timely exercise by Allarity of its option:

(i) any development milestone payments due from OncoHeroes to Allarity shall be cancelled,

and (ii) the parties shall enter into exclusive good faith negotiations regarding a fair market value (“FMV”) payment to

OncoHeroes which will take into account the value generated by OncoHeroes to the product, and may include a one-off payment to OncoHeroes

and royalties on future net sales for the product, or a one-time upfront payment, or such other FMV as the parties shall negotiate in

Option and License Agreement with R-Pharm for IXEMPRA ®

Ixempra work has been deprioritized by Allarity.

The newly installed leadership has not yet made a final decision on the Ixempra program.

Accordingly, these following sections remain for reference.

March 1, 2019, we entered into an option to in-license the rights to any and all therapeutic and/or diagnostic uses in humans for IXEMPRA ®

in the European Union (including Great Britain but excluding Switzerland and Lichtenstein) (the “Territory”) from

Operating, LLC (“R-Pharm”), pursuant to a Development, Option and License Agreement (the “Option”).

the execution of the agreement, we paid R-Pharm a non-refundable, non-creditable option payment of $100,000 and agreed to an anniversary

Upon the execution of the agreement, we paid R-Pharm a non-refundable, non-creditable option payment of $100,000 and agreed to an anniversary

payment of $250,000 on or before March 1, 2020, which we have paid.

Upon exercise of the option by us, we have agreed to pay R-Pharm an

exercise payment of $250,000.

Upon exercise of the option by us, we have agreed to pay R-Pharm

an exercise payment of $250,000.

By an amendment to the agreement effective August 4, 2022, the term of the option will expire on September

1, 2023, if not exercised by us before then.

As a condition to the exercise of the Option, we are required to offer R-Pharm a right to

re-acquire the licensed rights from us on terms to be mutually agreed upon, including the payment to us of the fair market value of the

licensed rights.

Pursuant to the Option, we are solely responsible for the development of IXEMPRA ® during the term

of the Option within the Territory.

The agreement also provides for a joint development committee consisting of four members, two appointed

As of the date of this filing, we have not extended the option with R-Pharm.

License and Development Agreement for Irofulven

May 2015 until July 23, 2021, we in-licensed various rights to Irofulven from Lantern Pharma, Inc.

pursuant to a drug license and

development agreement.

to the agreement, we were responsible for the development of Irofulven pursuant to a defined clinical development plan.

The agreement

also provides for a joint development committee, including representatives from Lantern Pharma and us, to regularly discuss, plan and

inform the development of products under the agreement.

In 2018, we commenced a DRP ® -guided Phase 2 clinical trial of

Irofulven in androgen receptor (AR)-targeted and Docetaxel-Pre-treated Metastatic Castration-Resistant Prostate Cancer (mCRPC) patients

using our putative Irofulven-DRP ® companion diagnostic to select and treat patients most likely to respond to the drug

(study SMR-365).

This trial was not completed and was an open-label, non-randomized, multi-center study in patients with docetaxel and

AR-targeted therapy pre-treated mCRPC.

Up to 27 mCRPC patients with predicted high probability of response to Irofulven (as determined

by the Irofulven-DRP ® companion diagnostic) were included.

A high likelihood of Irofulven response was defined as a patient

having an Irofulven-DRP ® score of >80%.

This study was suspended in 2019, when we deprioritized Irofulven as a therapeutic

candidate in order to devote more of our development resources to our priority therapeutic candidates, and on July 23, 2021, we terminated

our drug development agreement for Irofulven and sold our inventory of API, our clinical data and records, and our manufacturing know-how

relating to Irofulven to Lantern Pharma, and granted a non-exclusive license to Lantern Pharma to use our putative DRP ®

companion diagnostic specific for Irofulven.

Although we may be entitled to future milestone payments and royalties if Lantern Pharma

advances the development of Irofulven with or without our putative DRP ® companion diagnostic specific for Irofulven, we

will no longer devote any of our development resources to advance this therapeutic candidate.

Purchase Agreement between Allarity Therapeutics A/S and Lantern Pharma, Inc.

for Irofulven

work on Irofulven has been deprioritized.

The newly installed leadership at Allarity has not made final decisions on the Irofulven program.

Accordingly, these sections have been retained for reference.

July 23, 2021, we entered into an Asset Purchase Agreement with Lantern Pharma, Inc.

relating to our inventory of Irofulven active pharmaceutical

ingredients (“API”), our clinical research data relating to Irofulven developed by us during the drug development program

under the May 2015 Drug License and Development Agreement for Irofulven (the “Data”) and terminated our obligation to further

advance the development of Irofulven under the May 2015 agreement.

Under the Asset Purchase Agreement, Lantern Pharma agreed to pay us

$1 million on closing of the transaction, and additional amounts (i) when the inventory of Irofulven API is recertified with a longer

(ii) upon the initiation of treatment of the first patient in an investigator-led “compassionate use” ERCC2/3

mutation subgroup study using Irofulven in certain agreed upon investigators;

(iii) upon the first to occur of (x) initiation of treatment

of the first patient within an agreed upon time period after the closing of the transaction in any human clinical trial of Irofulven

initiated by Lantern Pharma for regulatory purposes, and (y) initiation of treatment of the 26 th patient in any human clinical

trial of Irofulven after the closing of the transaction initiated by Lantern Pharma or under the investigator-led study;

and (iv) upon

the initiation of treatment of the second patient within an agreed upon time period after the closing of the transaction in any human

clinical trial of Irofulven initiated by Lantern Pharma.

In addition to the sale of our inventory of Irofulven API and Data to Lantern

Pharma, we also granted Lantern Pharma a non-exclusive, worldwide license to use our putative Irofulven DRP ® companion

diagnostic to advance the development and commercialization of Irofulven and other Illudins (sesquiterpenes with anti-tumor properties

produced by some mushrooms).

We have also agreed not to engage in any drug development program for Illudins or any of its analogues or

any use thereof for a period of five years.

the Asset Purchase Agreement, we would also be entitled to receive certain milestone payments relating to our out-licensed putative Irofulven

DRP ® companion diagnostic upon the occurrence of the following events:

(i) upon the first use of our putative Irofulven

DRP ® companion diagnostic in a clinical trial for Irofulven;

and (ii) upon the first regulatory approval of our putative

Irofulven DRP ® companion diagnostic as a companion diagnostic for use with an approved drug.

In addition to the milestone

payments relating to our putative Irofulven DRP ® companion diagnostic, we would also be entitled to receive certain milestone

payments relating to the development and commercialization of Irofulven upon the occurrence of the following events:

(i) upon the first

filing for regulatory approval for commercialization of Irofulven in the United Kingdom, Germany, France and Italy, or upon the first

and second filings for regulatory approval for commercialization of Irofulven in countries located in the European Union that are not

Germany, France or Italy;

(ii) upon the first filing for regulatory approval for commercialization of Irofulven in the United States;

(iii) upon receiving the first regulatory approval for commercialization of Irofulven in the United Kingdom, Germany, France and

Italy, or upon the first and second receipts for regulatory approval for commercialization of Irofulven in countries located in the European

Union that are not Germany, France or Italy, (iv) upon receiving the first regulatory approval for commercialization of Irofulven

in the United States.

If all milestones have been achieved, then we would be entitled to receive up to $16 million in milestone payments

under the Asset Purchase Agreement.

addition to the milestone payments described above, Lantern Pharma has agreed to pay us royalties based on annual incremental net sales

of product derived from Irofulven, on a country by country basis, in an amount between 2% and 7% of annual sales of between $0 and $50

million, between 3% and 8% of annual sales between $50 million and $150 million, between 4% and 9% of annual sales between $150 million

and $300 million, and between 5% and 10% of annual sales in excess of $300 million.

royalty amounts we are entitled to receive may be subject to reduction in the event of generic competition, patent expiry, or if products

are (i) sold in the form of a combination product containing one or more active pharmaceutical ingredients which are not Irofulven or

(ii) sold under a bundled or capitated arrangement with one or more products which are not Irofulven or (iii) sold under an arrangement

whereby the sale of the product is only available with or conditioned upon the purchase of other products.

Agreement with 2-BBB Medicines B.V.

work on 2X-111 within Allarity has been de-prioritized.

New leadership has not yet made final decisions on the program.

The following

sections are retained for reference.

March 27, 2017, we in-licensed the exclusive worldwide rights to the central nervous system (“CNS”) and/or cerebrocardiovascular

drug application, including the (preventive) treatment of peripheral effects of agents causing CNS disease or symptoms, including cancer,

for 2X-111 from 2-BBB Medicines B.V.

(“2-BBB”) pursuant to a license agreement.

Upon execution of the agreement, we paid

2-BBB a one-time, non-refundable, non-creditable payment of $500,000.

Pursuant to the agreement, we are solely responsible for the development

of 2X-111 during the term of the agreement.

and Sales Milestone Payments

to the agreement, we have agreed to make milestone payments to 2-BBB in connection with the development of 2X-111 by us or our affiliates,

or by a third-party (a “Program Acquirer”) that assumes control of the 2X-111 development program from us corresponding to:

(i) enrollment of the first ten patients required in a Phase 2 clinical trial;

(ii) the successful completion of a Phase 2 clinical trial;

(iii) dosing of the first patient in the first Phase 3 clinical trial;

(iv) submission of the first NDA with the FDA;

(v) submission

of an MAA to the EMA in the European Union;

(vi) submission of an NDA in the first of either China or India;

(vii) receipt of the first

authorization by the FDA to market and sell a licensed product;

(viii) receipt of a MAA for a licensed product in the European Union;

and (ix) receipt of regulatory approval in the first of either China or India.

If all development milestones have been achieved, we may

be obligated to pay 2-BBB up to a maximum of $27.75 million which could increase to $55.5 million if 2-BBB successfully expands the field

of our license agreement to include all preventative, therapeutic and/or diagnostic uses related to cancer in humans.

In addition to

the development milestones described above, we have agreed to make a mid-level seven figure one-time payment upon our sales of a licensed

product reaching $500 million annually and a low eight figure payment upon the first and second time our sales of a licensed product

reaches $1 billion annually.

If all sales milestones have been achieved, we would be obligated to pay 2-BBB up to a maximum of $22.5

million which could increase to $45 million if 2-BBB successfully expands the field of our license agreement to include all preventative,

therapeutic and/or diagnostic uses related to cancer in humans.

addition to the milestone payments described above, we have agreed to pay 2-BBB royalties based on annual incremental sales of product

derived from 2X-111 in an amount between 5% and 10% of annual sales of between $0 and $100 million, between 6% and 13% of annual sales

between $100 million and $250 million, and between 7% and 13% of annual sales in excess of $250 million.

We are obligated to pay royalties

under the agreement on a product-by-product and country-by-country basis, from the period of time commencing on the first commercial

sale of any product in such country and expiring upon the latest of (a) the expiration of the last valid claim of a patent within (i)

the 2-BBB intellectual property and/or (ii) the joint intellectual property in such country (if, but only if, such joint intellectual

property arose from activities under the clinical development plan), or (b) the 10 th anniversary of the date of first commercial

sale of such product in such country.

However, the agreement may be sooner terminated without cause by us upon 120 days prior written

notice, or upon written notice of a material breach of the agreement by 2-BBB that is not cured within 90 days.

2-BBB also has the right

to terminate the agreement upon written notice of a material breach of the agreement by us that is not cured within 90 days (30 days

for a payment default) or if we file for bankruptcy.

2-BBB also has the right to terminate the agreement in the event we challenge a

2-BBB patent and we have the right to terminate the agreement upon 30 days’ notice for specified safety reason.

Agreement with SMERUD

June of 2020, we out-licensed our secondary LiPlaCis ® and 2X-111 programs to Smerud Medical Research International, our

long-time CRO partner in Europe, for further Phase 2 clinical development of each program together with its DRP ®

companion diagnostic.

On March 28, 2022, we restructured our LiPlaCis ® license agreements with Smerud and original drug

owner LiPlasome Pharma ApS, in a way that will enable Smerud to step into the shoes of Allarity and assume full control of this program

for further development in a Smerud affiliated subsidiary, Chosa ApS, and to secure additional investment funding and collaborative development

of the program through the affiliate.

Pursuant to the terms of the Support Agreement (as described below in the section titled “LiPlaCis

Support Agreement with Smerud, Chosa and LiPlasome”) and in connection with the termination of our exclusive licensee rights to

LiPlaCis ® under the Amended License Agreement (as described below in the section titled “Amended and Restated License

Agreement with LiPlasome Pharma ApS for LiPlaCis ® ”), we agreed to terminate our out-license agreement with SMERUD.

However, notwithstanding the termination of the out-license agreement, we are currently engaged in discussions with Smerud in connection

with the further development of 2X-111.

and Restated License Agreement with LiPlasome Pharma ApS for LiPlaCis ®

January 2021, we entered into an Amended and Restated License Agreement with LiPlasome Pharma ApS (“LiPlasome”) for the perpetual,

exclusive, world-wide rights to develop, use and market LiPlaCis ® for any indication which superseded all prior license

and development agreements between us and LiPlasome (the “Original License Agreement”).

On March 28, 2022, we entered into

an amended and restated license agreement which assigned, amended and restated the Original License Agreement, pursuant to which the

parties agreed to replace Allarity Europe with Chosa, an affiliate of Smerud, as exclusive licensee to further advance clinical development

and commercialization of LiPlaCis ® (the “Amended License Agreement”).

Under the Amended License Agreement,

Chosa replaced Allarity Europe as the exclusive licensee to the LiPlaCis ® technology.

In addition, Allarity Europe also

granted Chosa an exclusive, royalty-free, transferable and sublicensable license for (i) its DRP ® Companion Diagnostics

that are specific for Cisplatin or LiPlaCis ® for the research and development of LiPlaCis ® products, and

(ii) the use of any and all know-how and intellectual property rights owned by Allarity Europe for Chosa’s use of our DRP ®

Companion Diagnostics that are specific for Cisplatin or LiPlaCis ® for the development and commercialization of

LiPlaCis ® products, as contemplated in the Amended License Agreement.

Milestone Payments

to the Amended License Agreement, Allarity Europe is entitled to receive certain milestone payments from Chosa relating to the development

and commercialization of LiPlaCis ® upon the occurrence of the following events, which milestone payments are to be shared

with LiPlasome:

(i) receipt of first regulatory approval of a product in the United States, (ii) receipt of first regulatory approval

of a product in any country in Europe, including on a centralized filing basis by the EMA, (iii) the first achievement on a cumulative

basis of net sales of a product in the United States, and (iv) the first achievement on a cumulative basis of net sales of a product

in any country in Europe.

Each milestone payment is payable one time only, regardless of the number of times the corresponding milestone

event is achieved by a product and regardless of the number of products to achieve such milestone event.

If all milestones are achieved,

then we would be entitled to receive up to $3.5 million in milestone payments under the Amended License Agreement.

a result of the Amended License Agreement, we no longer have any rights to use or commercialize LiPlaCis ® and are only

entitled to receive the milestone payments upon the achievement of the respective milestones.

Support Agreement with Smerud, Chosa and LiPlasome

March 28, 2022, and concurrent with the entry into the Amended License Agreement, we entered into the LiPlaCis Support Agreement with

Allarity Europe, Smerud, Chosa and LiPlasome (the “Support Agreement”).

Pursuant to the terms of the Support Agreement, we

agreed (i) to pay to LiPlasome a certain percentage of the Commercialization Proceeds (as defined under the Original License Agreement)

we received from Smerud by way of debt cancellation relating to prior work on LiPlaCis ® by Smerud, which obligation

was to be satisfied by the payment of 2,273,020 Danish Kroner to LiPlasome upon execution of the Support Agreement, (ii) to equally share

the milestone payments under the terms of the Amended License Agreement, pursuant to which it was contemplated that upon the achievement

of all the milestones, our pro rata share of the milestone payments would be up to $3.5 million, (iii) to amend and restate the Original

License Agreement, and (iv) to terminate the Out-License Agreement with SMERUD as contemplated by the parties pursuant to the terms of

the Support Agreement.

Manufacturing

do not own or operate, and currently have no plans to establish, any manufacturing facilities.

We rely, and expect to continue to rely,

on third parties for the manufacture of our investigational products for preclinical and clinical testing, as well as for commercial

manufacture if any of our investigational products obtain marketing approval.

We also rely, and expect to continue to rely, on third

parties to package, label, store and distribute our investigational products, as well as for our commercial products if marketing approval

We believe that this strategy allows us to maintain a more efficient infrastructure by eliminating the need for us to invest

in our own manufacturing facilities, equipment and personnel while also enabling us to focus our expertise and resources on the development

of our investigational products.

date, we have obtained APIs and drug product for our investigational products from either the original drug owner/licensee or from single-source

third-party clinical manufacturing organizations (CMOs).

We are in the process of developing our supply chain for each of our investigational

products and intend to put in place framework agreements under which CMOs will generally provide us with necessary quantities of API

and drug product on a project-by-project basis based on our development needs, and which agreements will provide us with intellectual

property rights necessary to conduct the business.

We may use a different CMO for each investigational product and will consider further

diversification of drug product and supply organizations as circumstances warrant.

Overall, as we advance our investigational products

through development, we will start by seeking multiple sources for raw materials and address other potential points in concern over time.

Commercialization

intend to retain significant development and commercial rights to our investigational products and, if marketing approval is obtained,

to commercialize our investigational products on our own, or potentially with a partner, in the U.S.

and other regions, either globally

or on a region-by-region basis.

We do not intend to build the necessary infrastructure and sales, marketing and commercial product distribution

capabilities for the U.S., and potentially other regions, following further advancement of our investigational products.

We instead prefer

to build appropriate partnerships with marketing, sales, and distribution partners to effect launch and market penetration for each of

our therapeutic programs.

However, as we near approval and commercial launch of each program, we will assess the suitability of marketing

and sales partners and reserve the right to potentially develop and implement our own infrastructure to support the commercial success

of our programs.

Clinical data, the size of the addressable patient population and the size of the commercial infrastructure and manufacturing

needs and economics related to the foregoing may all influence or alter our commercialization plans.

pharmaceutical and biotechnology industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis

on proprietary products.

While we believe that our technology, development experience and scientific knowledge provide us with competitive

advantages, we face potential competition from many different sources, including large pharmaceutical and biotechnology companies, academic

institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and

establish collaborative arrangements for the research, development, manufacturing and commercialization of cancer therapies.

Any investigational

products that we successfully develop and commercialize will compete with new therapies that may become available in the future.

our core DRP ® platform technology, and any drug-specific DRP ® companion diagnostics that we develop and

commercialize, will compete with new companion diagnostic technologies that may become available in the future.

compete in the segments of the pharmaceutical, biotechnology and other related markets that develop small molecules and drug conjugates,

together with companion diagnostics, as treatments for cancer patients.

There are many other companies that have commercialized and/or

are developing such treatments for cancer including large pharmaceutical and biotechnology companies, such as AstraZeneca plc, Bristol-Myers

Squibb Company (“BMS”), Merck, Pfizer in partnership with Merck KGaA, Regeneron Pharmaceuticals, Inc.

in partnership with

Sanofi Genzyme (“Sanofi”) and Roche.

There are also many other companies that are developing, have developed, and/or have

commercialized patient-selective, companion diagnostic technologies/approaches for cancer patients, such as Foundation Medicine, Inc.,

Kura Oncology, Inc., and Lantern Pharma, Inc.

our Stenoparib program, we are aware of a number of companies that are currently marketing approved PARP inhibitors and/or developing

PARP inhibitors that are or may be competitive to our drug, such as Big Pharma companies AstraZeneca, BMS, Novartis, and GlaxoSmithKline

(GSK), and smaller pharmaceutical players BeiGene and Clovis Oncology.

To our knowledge, there is currently no approved or in development

PARP inhibitor, for the treatment of ovarian cancer or other indications, that has an identical therapeutic profile to stenoparib, with

or without its Stenoparib-DRP ® companion diagnostic.

our IXEMPRA ® program, we are aware of a number of companies that are currently marketing approved microtubule inhibitors

and/or developing microtubule inhibitors that are or may be competitive to our drug, such as Big Pharma companies Eisai and Sanofi, and

smaller pharmaceutical players like Celgene and Veru Pharma.

To our knowledge, there is currently no approved or in development microtubule

inhibitor, for the treatment of metastatic breast cancer (mBC) or other indications, that has an identical therapeutic profile to IXEMPRA ® ,

with or without its IXEMPRA ® -DRP ® companion diagnostic.

our LiPlaCis ® program, we are aware of a number of companies that are currently or have been developing liposomal formulations

of cisplatin that are or may be competitive to our drug, such as Regulon, Inc.

To our knowledge, there is currently no approved liposomal

formulation of cisplatin.

Furthermore, to our knowledge, there is no in development liposomal formulation of cisplatin, for the treatment

of mBC or other indications, that has an identical therapeutic profile to LiPlaCis ® , with or without its Cisplatin-DRP ®

companion diagnostic.

our 2X-111 program, we are aware of a number of companies that are currently marketing approved liposomal formulations of doxorubicin

and/or developing liposomal formulations of doxorubicin that are or may be competitive to our drug, such as Janssen Pharmaceuticals,

Baxter, and Teva, and Zydus Cadilla.

To our knowledge, there is currently no approved or in development Glutathione-modified liposomal

formulation of doxorubicin, for the treatment of GBM or other indications, that has an identical therapeutic profile to 2X-111, with

or without its Doxorubicin-DRP ® companion diagnostic.

our Irofulven-DRP ® companion diagnostic that we have out-licensed to Lantern Pharma, we are aware of a number of companies

that are currently marketing approved DNA damaging chemotherapeutics and/or developing DNA damaging chemotherapeutics that are or may

be competitive to Irofulven.

Many approved chemotherapeutics are now generic and sold by companies such as Teva Pharmaceuticals and Baxter.

Some smaller pharmaceutical companies, such as Alkido Pharma and Lantern Pharma, are attempting to develop novel chemotherapeutics.

Pharma, for example, is pre-clinically attempting to develop novel analogues of Irofulven.

To our knowledge, there is currently no approved

or in development DNA damaging agent, for the treatment of mCRPC or other indications, that has an identical therapeutic profile to Irofulven,

with or without its Irofulven-DRP ® companion diagnostic.

our core DRP ® platform technology (and its resulting drug specific DRP ® companion diagnostics), we are

aware of a number of companies that are currently marketing approved companion diagnostic platforms, or are attempting to develop such

platforms, that are or may be competitive to (although distinct from) our DRP ® platform, such as Foundation Medicine and

Lantern Pharma.

To our knowledge, there is currently no approved or developmental diagnostic technology or platform — for

the development of drug-specific companion diagnostics to guide selection and treatment of cancer patients most likely to respond to

a given drug — that is as broadly applicable, robust, and highly validated as our DRP ® platform.

of the companies against which we are competing or against which we may compete in the future have significantly greater financial resources

and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals,

and marketing approved drugs than we do.

Mergers and acquisitions in the pharmaceutical, biotechnology and diagnostic industries may

result in even more resources being concentrated among a smaller number of our competitors.

Smaller or early-stage companies may also

prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

These competitors

also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites

and enrolling subjects for our clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

could see a reduction or elimination of our commercial opportunity if our competitors develop and commercialize therapeutic products

that are safer or more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products

that we or our collaborators may develop.

Similarly, it is possible that our commercial opportunity may be reduced by the development

and commercialization of competing companion diagnostic products that are superior to our DRP ® companion diagnostics.

Our competitors also may obtain FDA or foreign regulatory approval for their products more rapidly than we may obtain approval for ours,

which could result in our competitors establishing a strong market position before we or our collaborators are able to enter the market.

The key competitive factors affecting the success of all our investigational products, if approved, are likely to be their degree of

anti-cancer activity, tolerability profile, convenience and price, the effectiveness of companion diagnostics (if required), the level

of biosimilar or generic competition and the availability of reimbursement from government and other third-party payors.

All these factors

will be impacted by the value and superiority of our DRP ® companion diagnostics over any competing companion diagnostic

approaches that currently exist or evolve in the oncology market.

authorities in the U.S.

at the federal, state, and local level and in other countries regulate, among other things, the research, development,

testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution,

post-approval monitoring and reporting, marketing and export and import of drug and biological products.

Generally, before a new drug

can be marketed, considerable data demonstrating its quality, safety and efficacy must be obtained, organized into a format specific

for each regulatory authority, submitted for review and approved by the regulatory authority.

Similar regulations and approvals exist

in the EU and other major oncology therapeutic markets.

Drug Development

the U.S., the FDA regulates drugs under the Food, Drug, and Cosmetic Act (“FDCA”).

Similarly, in the European Union (EU),

the European Medicines Agency (EMA) regulates the clinical trial, approval, and marketing of drugs.

Drugs also are subject to other federal,

state, and local statutes and regulations.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate

federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.

to comply with the applicable U.S.

or EU requirements at any time during the product development process, approval process or post-market

may subject an applicant to administrative or judicial sanctions.

These sanctions could include, among other actions, the FDA’s

or EMA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, untitled or warning letters, product

recalls or market withdrawals, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals

of government contracts, restitution, disgorgement and civil or criminal penalties.

Any agency or judicial enforcement action could have

a material adverse effect on us.

therapeutic candidates are considered small molecule drugs and must be approved by the FDA through the new drug application (“NDA”),

and similarly by the EMA under an equivalent process, before they may be legally marketed in the U.S.

The process generally involves

the following:

of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with GLP;

submission to the FDA of

an Investigational New Drug (IND) application, which must become approved and effective before human clinical trials may begin;

submission to the FDA of

an Investigational Device Exemption (IDE) application, which must become approved and effective before a drug-specific DRP ®

companion diagnostic can be used in human clinical trials;

approval by an independent

Institutional Review Board (IRB) or ethics committee at each clinical trial site before each trial may be initiated;

performance of adequate

and well controlled human clinical trials in accordance with applicable IND regulations, GCP requirements and other clinical trial-related

protocols and regulations to establish substantial evidence of the safety and efficacy of the investigational product for each proposed

submission to the FDA of

a NDA after completion of all pivotal trials;

submission to the FDA of

a Pre-Market Approval (PMA) application to allow use of a DRP ® companion diagnostic on the market together with its

approved drug;

determination by the FDA

within 60 days of its receipt of an NDA to accept the filing for substantive review;

satisfactory completion

of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug will be produced to assess compliance

with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength,

quality and purity;

potential FDA audit of

the pre-clinical study and/or clinical trial sites that generated the data in support of the NDA filing;

FDA review and approval

of the NDA, including consideration of the views of any FDA advisory committee, prior to any commercial marketing or sale of the

drug in the U.S.;

compliance with any post-approval

requirements, including the potential requirement to implement a REMS and the potential requirement to conduct post-approval studies.

data required to support an NDA are generated in two distinct developmental stages:

pre-clinical and clinical.

The pre-clinical and clinical

testing and approval process requires substantial time, effort, and financial resources, and we cannot be certain that any approvals

for any current and future therapeutic candidates will be granted on a timely basis, or at all, whether in the U.S, EU, or other region/country.

Studies and IND/IDE

preclinical developmental stage generally involves laboratory evaluations of drug chemistry, formulation, and stability, as well as studies

to evaluate toxicity in animals, which support subsequent clinical testing.

The sponsor must submit the results of the preclinical studies,

together with manufacturing information, retrospective data, any available clinical data or literature and a proposed clinical protocol,

to the FDA as part of the IND.

An IND is a request for authorization from the FDA to administer an investigational product to humans

and must become effective before human clinical trials may begin.

Similarly, and IDE is a request for authorization from the FDA to use

a diagnostic — in our case a DRP ® companion diagnostic — to screen, select, and treat specific patients

in a human clinical trial.

studies include laboratory evaluation of product chemistry and formulation, as well as in vitro and animal studies to assess the

potential for adverse events and in some cases to establish a rationale for therapeutic use.

The conduct of pre-clinical studies is subject

to federal regulations and requirements, including GLP regulations for safety/toxicology studies.

An IND sponsor must submit the results

of the pre-clinical tests, together with manufacturing information, retrospective data, any available clinical data or literature and

plans for clinical studies, among other things, to the FDA as part of an IND.

Similarly, an IDE sponsor must submit information about

the prior development and validation of the diagnostic, including results of the pre-clinical tests, together with manufacturing information,

retrospective data, any available clinical data or literature and plans for clinical studies, among other things, to the FDA as part

Some long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may continue

after the IND is submitted.

An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the

FDA raises concerns or questions related to one or more proposed clinical trials and places the trial on clinical hold.

In such a case,

the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.

As a result, submission of an

IND may not result in the FDA allowing clinical trials to commence.

Similarly, submission of an IDE for a DRP ® companion

diagnostic may not result in the FDA allowing use of such DRP ® in an approved clinical trial.

clinical stage of development involves the administration of the investigational product to healthy volunteers or patients under the

supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance

with GCP requirements, which include the requirement that all research subjects provide their informed consent for their participation

in any clinical trial.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial,

dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety and assess efficacy.

Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND.

Furthermore, each clinical

trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks

to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits.

also approve the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must

monitor the clinical trial until completed.

There also are requirements governing the reporting of ongoing clinical trials and completed

clinical trial results to public registries.

Clinical development in other major oncology markets, such as the EU, is subject to similar

requirements and regulations.

sponsor who wishes to conduct a clinical trial outside of the U.S.

may, but need not, obtain FDA authorization to conduct the clinical

trial under an IND.

If a foreign clinical trial is not conducted under an IND, the sponsor may submit data from the clinical trial to

the FDA in support of an NDA.

The FDA will generally accept a well-designed and well conducted foreign clinical trial not conducted under

an IND if the clinical trial is conducted in compliance with GCP and.

the FDA is able to validate the data through an onsite inspection,

if deemed necessary.

An NDA based solely on foreign clinical data meeting U.S.

criteria for marketing approval may be approved if (1) the

foreign data are applicable to the U.S.

population and U.S.

medical practice, (2) the studies have been performed by clinical investigators

of recognized competence and (3) the FDA is able to validate the data through an onsite inspection or other appropriate means, if

deemed necessary.

trials in the U.S.

generally are conducted in three sequential phases, known as Phase 1, Phase 2 and Phase 3, and may overlap.

Phase 1 clinical trials

generally involve a small number of healthy volunteers or disease-affected patients who are initially exposed to a single dose and

then multiple doses of the therapeutic candidate.

The primary purpose of these clinical trials is to assess the metabolism, pharmacologic

action, tolerability, and safety of the drug.

Phase 2 clinical trials

involve studies in disease-affected patients to determine the dose and dosing schedule required to produce the desired benefits.

At the same time, safety and further pharmacokinetic and pharmacodynamic information is collected, possible adverse effects and safety

risks are identified, and a preliminary evaluation of efficacy is conducted.

Phase 3 clinical trials

generally involve a large number of patients at multiple sites and are designed to provide the data necessary to demonstrate the

effectiveness of the product for its intended use, its safety in use and to establish the overall benefit/risk relationship of the

product and provide an adequate basis for product approval.

These trials may include comparisons with placebo and/or other comparator

The duration of treatment is often extended to mimic the actual use of a product during marketing.

Post-approval

trials, sometimes referred to as Phase 4 clinical trials, are conducted after initial marketing approval.

These trials are used to gain

additional experience from the treatment of patients in the intended therapeutic indication.

In certain instances, the FDA may mandate

the performance of Phase 4 clinical trials as a condition of approval of an NDA.

reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA.

is also responsible for submitting written IND safety reports, including reports of serious and unexpected suspected adverse events,

findings from other studies suggesting a significant risk to humans exposed to the drug, findings from animal or in vitro testing

that suggest a significant risk for human subjects, and any clinically significant increase in the rate of a serious suspected adverse

reaction over that listed in the protocol or investigator brochure.

Clinical development in other major oncology markets, such as the

EU, is subject to similar requirements and regulations.

1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all.

The FDA or the sponsor

may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects or patients

are being exposed to an unacceptable health risk.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution

if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with

unexpected serious harm to patients.

Additionally, some clinical trials are overseen by an independent group of qualified experts organized

by the clinical trial sponsor, known as a data safety monitoring board or committee.

This group provides authorization for whether a

trial may move forward at designated checkpoints based on access to certain data from the trial.

with clinical trials, companies may complete additional animal safety studies and must develop additional information about the chemistry

and physical characteristics of the drug as well as finalize a process for manufacturing the product in commercial quantities in accordance

with cGMP requirements.

The manufacturing process, as performed by the manufacturing facility, must be capable of consistently producing

quality batches of our therapeutic candidates.

Additionally, appropriate packaging must be selected and tested, and stability studies

must be conducted to demonstrate that our therapeutic candidates do not undergo unacceptable deterioration over their labeled shelf life.

Review Process

completion of the clinical trials, data is analyzed to assess whether the investigational product is safe and effective for the proposed

indicated use or uses.

The results of pre-clinical studies and clinical trials are then submitted to the FDA as part of an NDA, along

with proposed labeling, chemistry, and manufacturing information to ensure product quality and other relevant data.

In short, the NDA

is a request for approval to market the drug in the U.S.

for one or more specified indications and must contain proof of safety and efficacy

Concomitantly, a PMA is submitted to the FDA as part of NDA approval that is conditioned on use of a companion diagnostic.

In short, the PMA is a request for approval to market the companion diagnostic in the U.S., together with and required for prescription

of the drug, for one or more specified indications and must contain clinical evidence of safety and efficacy and sufficient validation

of the companion diagnostic used to select patients for treatment with the drug.

NDA application must include both negative and ambiguous results of preclinical studies and clinical trials, as well as positive findings.

Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s use or from a number

of alternative sources, including studies initiated by investigators.

To support marketing approval, the data submitted must be sufficient

in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of FDA.

of an NDA must be obtained before a drug may be legally marketed in the U.S.

Similarly, FDA approval of a PMA must be obtained before

a DRP ® companion diagnostic may be legally marketed in the U.S.

the Prescription Drug User Fee Act (“PDUFA”), as amended, each NDA must be accompanied by a user fee.

FDA adjusts the PDUFA

user fees on an annual basis.

PDUFA also imposes an annual program fee for each marketed human drug.

Fee waivers or reductions are available

in certain circumstances, including a waiver of the application fee for the first application filed by a small business.

Additionally,

no user fees are assessed on NDAs for products designated as orphan drugs, unless the product also includes a non-orphan indication.

FDA reviews all submitted NDAs before it accepts them for filing and may request additional information rather than accepting the NDA

The FDA must decide on accepting an NDA for filing within 60 days of receipt.

Once the submission is accepted for filing,

the FDA begins an in-depth review of the NDA.

Under the goals and policies agreed to by the FDA under PDUFA, the FDA has 10 months, from

the filing date, in which to complete its initial review of a new molecular-entity NDA and respond to the applicant, and six months from

the filing date of a new molecular-entity NDA designated for priority review.

The FDA does not always meet its PDUFA goal dates for standard

and priority NDAs, and the review process is often extended by FDA requests for additional information or clarification.

Similarly, the

FDA must decide on accepting a PMA for review within 45 days of receipt.

After acceptance, the FDA will begin substantive review

During the review process, FDA will notify the PMA applicant via major/minor deficiency letters of any information needed

by FDA to complete the review of the application.

FDA may refer the PMA to an outside panel of experts (advisory committee).

all PMAs for the first-of-a-kind device are taken before the appropriate advisory panel for review and recommendation.

approving an NDA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new product to determine whether

they comply with cGMP requirements.

The FDA will not approve the product unless it determines that the manufacturing processes and facilities

are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

The FDA also may audit data from clinical trials to ensure compliance with GCP requirements.

Additionally, the FDA may refer applications

for novel drug products or drug products which present difficult questions of safety or efficacy to an advisory committee, typically

a panel that includes clinicians and other experts, for review, evaluation, and a recommendation as to whether the application should

be approved and under what conditions, if any.

The FDA is not bound by recommendations of an advisory committee, but it considers such

recommendations when making decisions on approval.

The FDA likely will reanalyze the clinical trial data, which could result in extensive

discussions between the FDA and the applicant during the review process.

After the FDA evaluates an NDA, it will issue an approval letter

or a Complete Response Letter.

An approval letter authorizes commercial marketing of the drug with specific prescribing information for

specific indications.

A Complete Response Letter indicates that the review cycle of the application is complete, and the application

will not be approved in its present form.

A Complete Response Letter usually describes all of the specific deficiencies in the NDA identified

The Complete Response Letter may require additional clinical data, additional pivotal Phase 3 clinical trial(s) and/or other

significant and time-consuming requirements related to clinical trials, preclinical studies and/or manufacturing.

If a Complete Response

Letter is issued, the applicant may either resubmit the NDA, addressing all the deficiencies identified in the letter, or withdraw the

Even if such data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval.

Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently than we interpret the same data.

an IDE application is considered approved 30 days after it has been received by the FDA, unless the FDA otherwise informs the sponsor

via email prior to 30 calendar days from the date of receipt, that the IDE is approved, approved with conditions, or disapproved.

cases of disapproval, a sponsor can respond to the deficiencies.

the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition,

which is generally a disease or condition that affects fewer than 200,000 individuals in the U.S., or more than 200,000 individuals in

and for which there is no reasonable expectation that the cost of developing and making the product available in the U.S.

this type of disease or condition will be recovered from sales of the product.

drug designation must be requested before submitting an NDA.

After the FDA grants orphan drug designation, the identity of the therapeutic

agent and its potential orphan use are disclosed publicly by the FDA.

Orphan drug designation does not convey any advantage in or shorten

the duration of the regulatory review and approval process.

a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such

designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market

the same drug for the same indication for seven years from the date of such approval, except in limited circumstances, such as a showing

of clinical superiority to the product with orphan exclusivity by means of greater effectiveness, greater safety or providing a major

contribution to patient care or in instances of drug supply issues.

However, competitors may receive approval of either a different product

for the same indication or the same product for a different indication but that could be used off-label in the orphan indication.

drug exclusivity also could block the approval of one of our therapeutic candidates for seven years if a competitor obtains approval

before we do for the same product, as defined by the FDA, for the same indication we are seeking approval, or if a therapeutic candidate

is determined to be contained within the scope of the competitor’s product for the same indication.

If one of our therapeutic candidates

designated as an orphan drug receives marketing approval for an indication broader than that which is designated, it may not be entitled

to orphan drug exclusivity.

Orphan drug status in the European Union (EU) has similar, but not identical, requirements and benefits.

Development and Review Programs

FDA has a fast-track program that is intended to expedite or facilitate the process for reviewing new drugs that meet certain criteria.

Specifically, new drugs are eligible for fast-track designation if they are intended to treat a serious or life-threatening condition

and preclinical or clinical data demonstrate the potential to address unmet medical needs for the condition.

Fast track designation applies

to both the product and the specific indication for which it is being studied.

The sponsor can request the FDA to designate the product

for fast-track status any time before receiving NDA approval, but ideally no later than the pre-NDA meeting with the FDA.

product submitted to the FDA for marketing, including under a fast-track program, may be eligible for other types of FDA programs intended

to expedite development and review, such as priority review and accelerated approval.

Any product is eligible for priority review if

it treats a serious or life-threatening condition and, if approved, would provide a significant improvement in safety and effectiveness

compared to available therapies.

product may also be eligible for accelerated approval if it treats a serious or life-threatening condition and generally provides a meaningful

advantage over available therapies.

In addition, it must demonstrate an effect on a surrogate endpoint that is reasonably likely to predict

clinical benefit or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality (“IMM”),

which is reasonably likely to predict an effect on IMM or other clinical benefit.

As a condition of approval, the FDA may require that

a sponsor of a drug receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials.

FDA may withdraw

drug approval or require changes to the labeled indication of the drug if confirmatory post-market trials fail to verify clinical benefit

or do not demonstrate sufficient clinical benefit to justify the risks associated with the drug.

If the FDA concludes that a drug shown

to be effective can be safely used only if distribution or use is restricted, it may require such post-marketing restrictions as it deems

necessary to assure safe use of the product.

Additionally,

a drug may be eligible for designation as a breakthrough therapy if the product is intended, alone or in combination with one or more

other drugs or biologics, to treat a serious or life-threatening condition and preliminary clinical evidence indicates that the product

may demonstrate substantial improvement over currently approved therapies on one or more clinically significant endpoints.

of breakthrough therapy designation include the same benefits as fast-track designation, plus intensive guidance from the FDA to ensure

an efficient drug development program.

Fast track designation, priority review, accelerated approval and breakthrough therapy designation

do not change the standards for approval, but may expedite the development or approval process.

Even if a product qualifies for one or

more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the

time period for FDA review or approval will not be shortened.

Post-Approval

approval of a new product, the manufacturer and the approved product are subject to continuing regulation by the FDA, including, among

other things, monitoring and record-keeping requirements, requirements to report adverse events and comply with promotion and advertising

requirements, which include restrictions on promoting drugs for unapproved uses or patient populations, known as “off-label promotion,”

and limitations on industry-sponsored scientific and educational activities.

Although physicians may prescribe legally available drugs

for off-label uses, manufacturers may not market or promote such uses.

Prescription drug promotional materials must be submitted to the

FDA in conjunction with their first use.

Further, if there are any modifications to the drug, including changes in indications, labeling

or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new NDA or NDA supplement,

which may require the development of additional data or preclinical studies and clinical trials.

FDA may also place other conditions on approvals including the requirement for REMS, to assure the safe use of the product.

include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient

registries and other risk minimization tools.

Any of these limitations on approval or marketing could restrict the commercial promotion,

distribution, prescription or dispensing of products.

Product approvals may be withdrawn for non-compliance with regulatory standards

or if problems occur following initial marketing.

FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product

reaches the market.

Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity

or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved

labeling to add new safety information;

imposition of post-market studies or clinical studies to assess new safety risks or imposition

of distribution restrictions or other restrictions under a REMS program.

Other potential consequences include, among other things:

restrictions on the marketing

or manufacturing of the product, complete withdrawal of the product from the market, or product recalls;

fines, warning letters,

or holds on post-approval clinical studies;

refusal of the FDA to approve

pending applications or supplements to approved applications;

suspension or revocation

of product approvals;

product seizure or detention;

refusal to permit the import

or export of products;

injunctions or the imposition

of civil or criminal penalties.

FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market.

Drugs may be promoted

only for the approved indications and in accordance with the provisions of the approved label.

The FDA and other agencies actively enforce

the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label

uses may be subject to significant liability.

Marketing and promotion of approved drugs in other major oncology markets, such as the

EU, are subject to similar requirements and regulations.

Regulatory Matters

Pharmaceutical

manufacturers are subject to various healthcare laws, regulation, and enforcement by the federal government and by authorities in the

states and foreign jurisdictions in which they conduct their business.

Our conduct, including those of our employees, as well as our

business operations and relationships with third parties, including current and future arrangements with healthcare providers, third-party

payors, customers, and others may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations, which may

constrain the business or financial arrangements and relationships through which we research, as well as, sell, market, and distribute

any products for which we obtain marketing approval.

The applicable federal, state, and foreign healthcare laws and regulations that

may affect our ability to operate include, but are not limited to:

The federal Anti-Kickback

Statute, which makes it illegal for any person or entity, including a prescription drug manufacturer (or a party acting on its behalf),

to knowingly and willfully solicit, receive, offer or pay any remuneration that is intended to induce or reward referrals, including

the purchase, recommendation, order or prescription of a particular drug, for which payment may be made under a federal healthcare

program, such as Medicare or Medicaid.

Moreover, the PPACA provides that the government may assert that a claim including items or

services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of

the civil False Claims Act.

The federal false claims,

including the civil False Claims Act that can be enforced by private citizens through civil whistleblower or qui tam actions,

and civil monetary penalties law prohibit individuals or entities from, among other things, knowingly presenting, or causing to be

presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease

or conceal an obligation to pay money to the federal government.

HIPAA prohibits, among

other things, executing or attempting to execute a scheme to defraud any healthcare benefit program or making false statements relating

to healthcare matters.

HIPAA, as amended by HITECH,

and their implementing regulations also impose obligations on covered entities such as health insurance plans, healthcare clearinghouses,

and certain healthcare providers and their respective business associates and their covered subcontractors, including mandatory contractual

terms, with respect to safeguarding the privacy, security, and transmission of individually identifiable health information.

The federal Physician Payments

Sunshine Act requires applicable manufacturers of covered drugs, devices, biologics and medical supplies for which payment is available

under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to annually report to CMS information

regarding certain payments and other transfers of value to physicians, as defined by such law, and teaching hospitals as well as

information regarding ownership and investment interests held by physicians and their immediate family members;

additionally, the

Substance Use-Disorder Prevention that Promoted Opioid Recovery and Treatment for Patients and Communities Act, under the provision

titled “Fighting the Opioid Epidemic with Sunshine,” in part, extends the reporting and transparency requirements for

physicians under the Physician Payments Sunshine Act to physician assistants, nurse practitioners, and other mid-level practitioners,

with reporting requirements going into effect in 2022 for payments made, or ownership and investment interests held, in 2021.

Analogous state and foreign

laws and regulations, such as state anti-kickback and false claims laws which may apply to sales or marketing arrangements and claims

involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, state laws

that require biotechnology companies to comply with the biotechnology industry’s voluntary compliance guidelines and the relevant

compliance guidance promulgated by the federal government;

state and local laws that require drug manufacturers to report information

related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures and require

the registration of their sales representatives, state laws that require biotechnology companies to report information on the pricing

of certain drug products, and state and foreign laws that govern the privacy and security of health information in some circumstances,

many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

and rebate programs must also comply with the Medicaid rebate requirements of the U.S.

Omnibus Budget Reconciliation Act of 1990 and

more recent requirements in the PPACA.

If products are made available to authorized users of the Federal Supply Schedule of the General

Services Administration, additional laws and requirements apply.

Manufacturing, sales, promotion, and other activities also are potentially

subject to federal and state consumer protection and unfair competition laws.

In addition, the distribution of pharmaceutical products

is subject to additional requirements and regulations, including extensive record-keeping, licensing, storage, and security requirements

intended to prevent the unauthorized sale of pharmaceutical products.

Products must meet applicable child-resistant packaging requirements

under the U.S.

Poison Prevention Packaging Act as well as other applicable consumer safety requirements.

failure to comply with any of these laws or regulatory requirements subjects firms to possible legal or regulatory action.

on the circumstances, failure to meet applicable regulatory requirements can result in significant civil, criminal and administrative

penalties, including damages, fines, disgorgement, imprisonment, exclusion from participation in government funded healthcare programs,

such as Medicare and Medicaid, integrity oversight and reporting obligations, contractual damages, reputational harm, diminished profits

and future earnings, injunctions, requests for recall, seizure of products, total or partial suspension of production, denial or withdrawal

of product approvals or refusal to allow a firm to enter into supply contracts, including government contracts.

promotion, and sale of approved drugs in other major oncology markets, such as the EU, are subject to similar requirements and regulations.

For example, in the EU, safeguarding the privacy, security and transmission of individually identifiable health information is subject

to the General Data Protection Regulation (GDPR) and laws, which are widely considered to be the most stringent in the world.

Patent-Term Restoration and Marketing Exclusivity

upon the timing, duration, and specifics of FDA approval of any future therapeutic candidates, some of our U.S.

patents, if issued, may

be eligible for limited patent term extension under the Hatch-Waxman Act.

The Hatch-Waxman Act permits restoration of the patent term

of up to five years as compensation for the lost opportunity to market the drug during the patent term while the drug was under the FDA

regulatory review process.

Patent-term restoration, however, cannot extend the remaining term of a patent beyond a total of 14 years

from regulatory approval.

The patent-term restoration period is generally one-half the time between the effective date of an IND or the

issue date of the patent, whichever is later, and the submission date of an NDA plus the time between the submission date of an NDA or

the issue date of the patent, whichever is later, and the approval of that application, except that the review period is reduced by any

time during which the applicant failed to exercise due diligence.

Only one patent applicable to an approved drug is eligible for the

extension and the application for the extension must be submitted prior to the expiration of the patent.

The US Patent Office (USPTO),

in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

In the future, we may

apply for restoration of patent term for our currently owned or licensed patents to add patent life beyond its current expiration date,

depending on the expected length of the clinical trials and other factors involved in the filing of the relevant NDA.

exclusivity provisions under the FDCA also can delay the submission or the approval of certain applications.

The FDCA provides a five-year

period of non-patent marketing exclusivity within the U.S.

to the first applicant to gain approval of an NDA for a new chemical entity.

A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is

the molecule or ion responsible for the action of the drug substance.

During the exclusivity period, the FDA may not accept for review

an abbreviated new drug application (“ANDA”), or a 505(b)(2) NDA submitted by another company for a generic version of such

drug where the applicant does not own or have a legal right of reference to all the data required for approval.

However, an application

may be submitted after four years if it contains a certification of patent invalidity or non-infringement.

The FDCA also provides three

years of marketing exclusivity for an NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than

bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the

application, for example, new indications, dosages, or strengths of an existing drug.

This three-year exclusivity covers only the conditions

of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original

active agent.

Five-year and three-year exclusivity will not delay the submission or approval of a full NDA.

However, an applicant submitting

a full NDA would be required to conduct or obtain a right of reference to all the preclinical studies and adequate and well-controlled

clinical trials necessary to demonstrate safety and effectiveness or generate such data themselves.

Union Drug Development

to the United States, the various phases of preclinical and clinical research in the European Union are subject to significant regulatory

Although the EU Clinical Trials Directive 2001/20/EC has sought to harmonize the EU clinical trials regulatory framework, setting

out common rules for the control and authorization of clinical trials in the EU, the EU Member States have transposed and applied the

provisions of the Directive differently.

This has led to significant variations in the member state regimes.

Under the current regime,

before a clinical trial can be initiated, it must be approved in each of the EU countries where the trial is to be conducted by two distinct

the National Competent Authority (“NCA”), and one or more Ethics Committees (“ECs”).

Under the current

regime all suspected unexpected serious adverse reactions to the investigated drug that occur during the clinical trial have to be reported

to the NCA and ECs of the Member State where they occurred.

EU clinical trials legislation currently is undergoing a transition process mainly aimed at harmonizing and streamlining clinical-trial

authorization, simplifying adverse-event reporting procedures, improving the supervision of clinical trials and increasing their transparency.

Recently enacted Clinical Trials Regulation EU No 536/2014 ensures that the rules for conducting clinical trials in the EU will be identical.

In the meantime, Clinical Trials Directive 2001/20/EC continues to govern all clinical trials performed in the EU.

Union Drug Review and Approval

the European Economic Area (“EEA”), which comprises the 28 Member States of the European Union and three European Free Trade

Association States (Norway, Iceland, and Liechtenstein), medicinal products can only be commercialized after obtaining a Marketing Authorization

There are two types of MAs.

The Community MA is issued

by the European Commission through the Centralized Procedure, based on the opinion of the Committee for Medicinal Products for Human

Use, of the EMA, and is valid throughout the entire territory of the EEA.

The Centralized Procedure is mandatory for certain types

of products, such as biotechnology medicinal products, orphan medicinal products, advanced-therapy medicines such as gene-therapy,

somatic cell-therapy or tissue-engineered medicines and medicinal products containing a new active substance indicated for the treatment

of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions, and viral diseases.

The Centralized

Procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute

a significant therapeutic, scientific, or technical innovation or which are in the interest of public health in the EU.

National MAs, which are

issued by the competent authorities of the Member States of the EEA and only cover their respective territory, are available for

products not falling within the mandatory scope of the Centralized Procedure.

Where a product has already been authorized for marketing

in a Member State of the EEA, this National MA can be recognized in another Member States through the Mutual Recognition Procedure.

If the product has not received a National MA in any Member State at the time of application, it can be approved simultaneously in

various Member States through the Decentralized Procedure.

Under the Decentralized Procedure an identical dossier is submitted to

the competent authorities of each of the Member States in which the MA is sought, one of which is selected by the applicant as the

Reference Member State (“RMS”).

The competent authority of the RMS prepares a draft assessment report, a draft summary

of the product characteristics (“SOPC”), and a draft of the labeling and package leaflet, which are sent to the other

Member States (referred to as the Member States Concerned) for their approval.

If the Member States Concerned raise no objections,

based on a potential serious risk to public health, to the assessment, SOPC, labeling or packaging proposed by the RMS, the product

is subsequently granted a national MA in all the Member States (i.e., in the RMS and the Member States Concerned).

the above-described procedures, before granting the MA, EMA or the competent authorities of the Member States of the EEA assess the risk-benefit

balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.

Like the U.S.

patent term-restoration,

Supplementary Protection Certificates (“SPCs”) serve as an extension to a patent right in Europe for up to five years.

apply to specific pharmaceutical products to offset the loss of the ability to market a drug during the patent term due to the lengthy

testing and clinical trials these products require prior to obtaining regulatory marketing approval.

and Reimbursement

of our therapeutic products and DRP ® companion diagnostics, if approved, will depend, in part, on the extent to which

our products will be covered by third-party payors, such as government health programs, commercial insurance and managed healthcare organizations.

There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved products.

In the U.S., for

example, principal decisions about reimbursement for new products are typically made by CMS.

CMS decides whether and to what extent a

new product will be covered and reimbursed under Medicare, and private third-party payors often follow CMS’s decisions regarding

coverage and reimbursement to a substantial degree.

However, no uniform policy of coverage and reimbursement for drug products exists.

Accordingly, decisions regarding the extent of coverage and amount of reimbursement to be provided for any of our products will be made

on a payor-by-payor basis.

Increasingly,

third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the

prices charged for medical products.

Further, such payors are increasingly challenging the price, examining the medical necessity and

reviewing the cost effectiveness of medical therapeutic candidates.

There may be especially significant delays in obtaining coverage

and reimbursement for newly approved drugs.

Third-party payors may limit coverage to specific therapeutic candidates on an approved list,

known as a formulary, which might not include all FDA-approved drugs for a particular indication.

We may need to conduct expensive pharmacoeconomic

studies to demonstrate the medical necessity and cost effectiveness of our products.

As a result, the coverage determination process

is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products

to each payor separately, with no assurance that coverage and adequate reimbursement will be obtained.

Additionally, coverage policies

and third-party reimbursement rates may change at any time.

Even if favorable coverage and reimbursement status is attained for one or

more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in

Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (“MMA”), established the Medicare Part D program to

provide a voluntary prescription drug benefit to Medicare beneficiaries.

Under Part D, Medicare beneficiaries may enroll in prescription

drug plans offered by private entities that provide coverage of outpatient prescription drugs.

Unlike Medicare Part A and B, Part D coverage

is not standardized.

While all Medicare drug plans must give at least a standard level of coverage set by Medicare, Part D prescription

drug plan sponsors are not required to pay for all covered Part D drugs, and each drug plan can develop its own drug formulary that identifies

which drugs it will cover and at what tier or level.

However, Part D prescription drug formularies must include drugs within each therapeutic

category and class of covered Part D drugs, though not necessarily all the drugs in each category or class.

Any formulary used by a Part

D prescription drug plan must be developed and reviewed by a pharmacy and therapeutic committee.

Government payment for some of the costs

of prescription drugs may increase demand for products for which we receive marketing approval.

However, any negotiated prices for our

products covered by a Part D prescription drug plan likely will be lower than the prices we might otherwise obtain.

Moreover, while the

MMA applies only to drug benefits for Medicare beneficiaries, private third-party payors often follow Medicare coverage policy and payment

limitations in setting their own payment rates.

addition, where a drug product requires a companion diagnostic (in our case, a DRP ® companion diagnostic), then companion

diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical

or biological products.

Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical or biological products,

will apply to companion diagnostics.

In general, insurance payors will cover and reimburse a companion diagnostic where sufficient clinical

proof is provided to support that use of the companion diagnostic improves healthcare outcomes and/or reduces healthcare expenses associated

with a given drug.

addition, in most foreign countries, the proposed pricing for a drug must be approved before it may be lawfully marketed.

The requirements

governing drug pricing and reimbursement vary widely from country to country.

For example, the European Union provides options for its

member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and

to control the prices of medicinal products for human use.

A member state may approve a specific price for the medicinal product, or

it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will

allow favorable reimbursement and pricing arrangements for any of our products.

Historically, products launched in the European Union

do not follow price structures of the U.S.

and generally prices tend to be significantly lower.

government, state legislatures and foreign governments have shown significant interest in implementing cost containment programs

to limit the growth of government-paid healthcare costs, including price-controls, restrictions on reimbursement and requirements for

substitution of generic products for branded prescription drugs.

For example, the PPACA substantially changed the way healthcare is financed

by both the government and private insurers and continues to significantly impact the U.S.

pharmaceutical industry.

The PPACA contains

provisions that may reduce the profitability of drug products through increased rebates for drugs reimbursed by Medicaid programs, extension

of Medicaid rebates to Medicaid managed care plans, mandatory discounts for certain Medicare Part D beneficiaries and annual fees based

on pharmaceutical companies’ share of sales to federal healthcare programs.

The Medicaid Drug Rebate Program requires pharmaceutical

manufacturers to enter into and have in effect a national rebate agreement with the HHS Secretary as a condition for states to receive

federal matching funds for the manufacturer’s outpatient drugs furnished to Medicaid patients.

The PPACA made several changes to

the Medicaid Drug Rebate Program, including increasing pharmaceutical manufacturers’ rebate liability by raising the minimum basic

Medicaid rebate on most branded prescription drugs from 15.1% of average manufacturer price (“AMP”), to 23.1% of AMP and

adding a new rebate calculation for “line extensions” (i.e., new formulations, such as extended release formulations) of

solid oral dosage forms of branded products, as well as potentially impacting their rebate liability by modifying the statutory definition

The PPACA also expanded the universe of Medicaid utilization subject to drug rebates by requiring pharmaceutical manufacturers

to pay rebates on Medicaid managed care utilization and by enlarging the population potentially eligible for Medicaid drug benefits.

Additionally, for a drug product to receive federal reimbursement under the Medicaid or Medicare Part B programs or to be sold directly

government agencies, the manufacturer must extend discounts to entities eligible to participate in the 340B drug pricing program.

The required 340B discount on a given product is calculated based on the AMP and Medicaid rebate amounts reported by the manufacturer.

remain judicial and Congressional challenges to certain aspects of the PPACA, as well as efforts by the previous administration to repeal

or replace certain aspects of the PPACA.

Since January 2017, there have been several executive orders and other directives designed

to delay the implementation of certain provisions of the PPACA or otherwise circumvent some of the requirements for health insurance

mandated by the PPACA.

Concurrently, Congress has considered legislation that would repeal or repeal and replace all or part of the PPACA.

While Congress has not passed comprehensive repeal legislation, several bills affecting the implementation of certain taxes under the

PPACA have passed.

In 2017, the Tax Act repealed, effective January 1, 2019, the tax-based shared responsibility payment imposed by the

PPACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as

the “individual mandate.” In addition, the 2020 federal spending package permanently eliminated, effective January 1, 2020,

the PPACA’s mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective

January 1, 2021, also eliminates the health insurer tax.

The Bipartisan Budget Act of 2018, among other things, amended the PPACA, effective

January 1, 2019, to close the coverage gap in most Medicare Part D drug plans.

In December 2018, CMS published a new final rule

permitting further collections and payments to and from certain ACA-qualified health plans and health insurance issuers under the PPACA

risk adjustment program in response to the outcome of federal district court litigation regarding the method CMS uses to determine this

risk adjustment.

In April 2020, the U.S.

Supreme Court reversed a federal circuit decision that previously upheld Congress’

denial of $12.0 billion in “risk corridor” funding.

In December 2018, a Texas U.S.

District Court Judge ruled that the

PPACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress as part of the Tax Act.

Additionally, in December 2019, the U.S.

Court of Appeals for the Fifth Circuit upheld the District Court ruling that the individual

mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the PPACA

are invalid as well.

On June 17, 2021, the U.S.

Supreme Court reversed the decision of the Fifth Circuit holding that the state plaintiffs

lacked standing to challenge the individual mandate under Article III, Section 2 of the U.S.

Constitution.

It is unclear how future litigation

and other efforts to repeal and replace the PPACA will impact the PPACA and our business.

We will continue to evaluate the effect that

the PPACA and its possible repeal and replacement has on our business.

Complying with any new legislation, resulting in a material adverse

effect on our business.

legislative changes have been proposed and adopted in the U.S.

since the PPACA was enacted.

These changes included aggregate reductions

to Medicare payments to providers of up to 2% per fiscal year, effective April 1, 2013, which, due to subsequent legislative amendments,

will stay in effect through 2030 unless additional congressional action is taken.

The CARES Act, which was signed into law in March 2020,

and designed to provide financial support and resources to individuals and businesses affected by COVID-19 pandemic, suspended the 2%

Medicare sequester from May 1, 2020, through December 31, 2020, and extended the sequester by one year, through 2030, to offset the added

expense of the 2020 suspension.

The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers

and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

new laws may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on

customers for our drugs, if approved, and accordingly, our financial operations.

Additionally,

there has been heightened governmental scrutiny recently over the way drug manufacturers set prices for their marketed products, which

has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things,

bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform

government program reimbursement methodologies for drug products.

For example, at the federal level, the administration’s budget

proposals for fiscal year 2021 includes a $135 billion allowance to support legislative proposals seeking to reduce drug prices,

increase competition, lower out-of-pocket drug costs for patients, and increase patient access to lower-cost generic and biosimilar drugs.

On March 10, 2020, the administration sent “principles” for drug pricing to Congress, calling for legislation that would,

among other things, cap Medicare Part D beneficiary out-of-pocket pharmacy expenses, provide an option to cap Medicare Part D beneficiary

monthly out-of-pocket expenses, and place limits on pharmaceutical price increases.

Additionally, the administration previously released

a “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that contained proposals to increase manufacturer

competition, increase the negotiating power of certain federal healthcare programs, incentivize manufacturers to lower the list price

of their products and reduce the out-of-pocket costs of drug products paid by consumers.

Although a number of these and other measures

may require additional authorization to become effective, Congress and the administration have each indicated that it will continue to

seek new legislative and/or administrative measures to control drug costs.

For example, on July 24, 2020, the administration announced

four executive orders to lower drug prices, including allowing importation of certain drugs, changing how drug rebates are negotiated

by middlemen, like pharmacy benefit managers, and directing such rebates to be passed to patients as point-of-sale discounts, and requiring

Medicare to pay certain Part B drugs at the lowest price available in economically comparable countries (the details of which were released

on September 13, 2020 and also expanded the policy to cover certain Part D drugs).

The president has delayed the effective date of the

international drug pricing order, pending discussion with major drug companies.

How these executive orders will be implemented and their

impact on the industry remain uncertain.

Additionally, the FDA recently released a final rule, effective November 30, 2020, implementing

a portion of the importation executive order providing guidance for states to build and submit importation plans for drugs from Canada.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical

and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access

and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and

bulk purchasing.

It is possible that additional governmental action is taken in response to the ongoing COVID-19 pandemic, which may

impact our business.

We are unable to predict the future course of federal or state healthcare legislation in the U.S.

directed at broadening

the availability of healthcare and containing or lowering the cost of healthcare.

These and any further changes in the law or regulatory

framework that reduce our revenue or increase our costs could also have a material and adverse effect on our business, financial condition,

and results of operations.

principal executive office is in Boston, MA USA, where we lease at-will, month-to-month share space where we are not bound by any lease.

This office is sufficient to support our U.S.-based executive team members, most of whom are based on the East Coast of the U.S., including

our CEO, CMO, and SVP of Corporate Development.

Our principal laboratory and R&D facility is in Hoersholm, Denmark (just north of

Copenhagen), where we have a modest space in a technology park, with an open-ended facility lease, which terminates upon 12-month notice.

We believe that these existing facilities will be adequate for our current needs and that suitable additional or alternative space will

be available in the future on commercially reasonable terms, if required.

of March 1, 2024, we had 6 employees, 5 of whom were full-time and 1 half-time;

and most of which were engaged in research and development

Of our employees, the majority are in Hoersholm, Denmark.

Among our executive management team members, one is located near

New York City, NY, and one is in Vancouver, British Columbia, Canada.

None of our employees are represented by labor unions or covered

by collective bargaining agreements.

We consider our relationship with our employees to be good.

recognize that attracting, motivating, and retaining talent at all levels is vital to our continued success.

Our employees are a significant

asset, and we aim to create an environment that is equitable, inclusive, and representative in which our employees can grow and advance

their careers, with the overall goal of developing, expanding, and retaining our workforce to support our current pipeline and future

business goals.

By focusing on employee retention and engagement, we also improve our ability to support our clinical-stage platform,

business, and operations, and also protect the long-term interests of our securityholders.

Our success also depends on our ability to

attract, engage, and retain a diverse group of employees.

Our efforts to recruit and retain a diverse and passionate workforce include

providing competitive compensation and benefits packages and ensuring we listen to our employees.

value agility, passion, and teamwork, and are building a diverse environment where our employees can thrive and one that inspires exceptional

contributions and professional and personal development to achieve our mission to significantly change the practice of oncology.

human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing, and integrating our existing

and new employees, advisors and consultants.

The principal purposes of our equity and cash incentive plans are to attract, retain and

reward personnel through the granting of stock-based and cash-based compensation awards, to increase stockholder value and the success

of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

We are committed

to providing a competitive and comprehensive benefits package to our employees.

Our benefits package provides a balance of protection

along with the flexibility to meet the individual health and wellness needs of our employees.

plan to continue to develop our efforts related to attracting, retaining, and motivating our workforce as we grow and develop and hire

more employees.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business