What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2023-03-13 compared with 2022-05-17 · 2544 added, 2544 removed, 1456 unchanged (78% 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 biopharmaceutical

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, 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.

As used in this Annual Report, statements regarding

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

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.

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

1 unchanged sentence

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 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 lead therapeutic candidate, dovitinib, a second-generation “pan”-tyrosine

kinase inhibitor (TKI), on December 21, 2021, which was subsequently determined by the FDA to be not sufficiently complete to permit a

substantive review and therefore was not accepted for filing.

As discussed further below, we have requested a meeting with the FDA to

discuss the nature and extent of additional clinical data, which is likely to include one or more additional clinical trials, that will

be necessary to substantiate a complete NDA application.

Concurrently with the FDA’s conclusion on our NDA, the FDA also made a

similar determination on our application for a PMA on our companion diagnostic for dovitinib.

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.

We were founded in Denmark in 2004 by our chief scientific officer, Steen Knudsen, Ph.D., and our Senior Vice President of Information

Technologies, 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.

We completed our Recapitalization

Share Exchange and listing on Nasdaq acquiring substantially all of the assets and assuming substantially all of the

liabilities of our predecessor, Allarity Therapeutics A/S on December 20, 2021.

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

though 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

Our lead 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

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 ®

5 unchanged sentences

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 Allarity’s 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

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.

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 Company plans to have discussions with the FDA during the

second quarter of 2022 to clarify a path forward for approval of this lead program.

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

4 unchanged sentences

(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 the Dana-Farber Cancer Institute (Boston, MA USA), along with additional trial sites

and Europe) together with its stenoparib-specific DRP ® companion diagnostic, for which the FDA has previously

approved an Investigational Device Exemption (IDE) application.

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.

(ixabepilone) was formerly developed and brought to market by Bristol-Myers Squibb, is currently marketed and sold in the U.S.

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.

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.

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 significant 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 entities.

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.

Further 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 lead 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

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.

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,

11 unchanged sentences

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

A precision oncology approach:

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 approach.

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 development.

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 the Recapitalization Share Exchange, a PIPE Financing with

the Investor, and migrating the trading in our shares from the Nasdaq First North Growth Market:

Stockholm to Nasdaq in the U.S.

20, 2021, we entered into 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 A/S.

The shareholders of Allarity

Therapeutics 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 (the

“Purchase Agreement”), 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 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 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.

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 Sub.

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 the Investor wherein we agreed to sell, and the Investor agreed to purchase, 20,000 shares of our Series A Preferred Stock

(the “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 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 File No.

333-259484), which was

declared effective on December 20, 2021.

Under the terms of the RRA, if we 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 equal to 2% of the Investor’s

investment upon our failure to maintain the effectiveness of the registration statement and every thirty (30) days thereafter.

to maintain the effectiveness of the registration statement also constitutes a “triggering event” under the COD for the Preferred

Shares that would result in the accrual and payment of a dividend and provide the Investor the right to have its remaining Preferred Shares

redeemed for a premium of a minimum of 125% of the Conversion Amount of the Preferred Shares, 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 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 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 ten (10) trading day period

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

Maximum Failure”), each share of Preferred Stock is entitled to convert at a price equal to 90% of the sum of the two (2) lowest

VWAPs during the ten (10) trading day period immediately preceding delivery divided by two (2) (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 ten (10) days previous to conversion divided by ten (10) is less than $2,000,000 (a “Volume

Alternate Failure”), then each share of 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 (2) lowest VWAPs during the ten (10) trading day period immediately preceding delivery divided by two

(2) (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 COD

occur, such as a breach of the Registration Rights Agreement, suspension of trading, or our failure to convert the Preferred Shares 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 COD), then we may be required to pay a dividend that is added to the stated value on the 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 Preferred

Stock for cash in an amount of a minimum of 125% of the Conversion Amount (as defined in the COD) of the Preferred Stock or 125% of the

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

event that we experience a “Change of Control” (as defined in the COD) we may also be required to redeem the Preferred Shares

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 ten (10) days previous to conversion divided by ten (10) is less than $2,500,000, then

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

$80 increase per share in stated value, resulting in a stated value of $1,080 per share of 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.

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 COD 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 COD and the Investor’s legal fees incurred in the preparation of the Forbearance

Agreement and Waiver in the aggregate of $538,823.00 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 COD that arises as a result of a Triggering

Event under Section 5(a)(ii) of the COD 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 COD (excluding any Triggering Event arising solely as a result of Section 5(a)(ii) of the COD 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 (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 date the Company

cures the Triggering Event under Section 5(a)(ii) of the COD, the Investor agrees to waive any rights or remedies that it may have under

the COD that arises as a result of a Triggering Event under Section 5(a) of the COD and Section 4(c)(ii) of the PIPE Warrant that may

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

Recent Business Development

License Agreements

with Oncoheroes

January 2022, we entered into certain exclusive license agreements (collectively, the “License Agreements”) with Oncoheroes

Biosciences, Inc.

(“Oncoheroes”).

Under the License Agreements, Oncoheroes will acquire exclusive, global development rights

to our therapeutic candidates Dovitinib, a pan-targeted kinase inhibitor (pan-TKI), and Stenoparib, a PARP inhibitor, and assume responsibility

for their further clinical development in the field of pediatric cancers.

As part of the License Agreements, Oncoheroes will receive commercialization

rights for pediatric cancers, subject to our first buy-back option for each program, and we will receive upfront license fees and regulatory

milestones for each program.

If we do not re-acquire the pediatric field rights, we will further receive certain clinical/regulatory milestone

payments and royalties on sales of Stenoparib and Dovitinib in the pediatric cancer market from Oncoheroes.

Development Milestone

Under the License Agreements,

we would also be entitled to receive certain milestone payments relating to the development and commercialization of Dovitinib and Stenoparib

upon the occurrence of the following events:

(i) upon the regulatory approval of a product in the United States, and (ii) upon the

regulatory approval of a product in the European Union.

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 $2 million in milestone payments under each respective License

Royalty Payments

addition to the milestone payments described above, Oncoheroes has agreed to pay us royalties based on aggregate annual net sales of all

products derived from Dovitinib and Stenoparib during the royalty term which is determined on a country-by-country and product-by-product

basis, as 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) our 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 defined in the

agreement), or (b) the fifteenth (15th) anniversary of the date of first commercial sale of such licensed drug in such country.

be entitled to royalty payments of between three percent (3%) and eight percent (8%) of annual net sales of between $0 and $100 million,

between six percent (6%) and eleven percent (11%) of annual net sales between $100 million and $200 million, and between eight percent

(8%) and thirteen percent (12%) of annual net sales in excess of $200 million.

The royalty amounts we are entitled to receive may be subject

to reduction in the event a product is not covered by a valid claim of a licensed patent in such country.

License Agreements with Oncoheroes will continue on a product-by-product and country-by-country basis until the expiration of the applicable

royalty term described above.

However, the License Agreements may be terminated by Oncoheroes at any time after the first anniversary

of the effective date of each License Agreement for any or no reason upon (i) ninety (90) days’ written notice if such notice is

provided prior to first commercial sale, and (ii) one hundred eighty (180) days’ written notice if such notice is provided on or

after the first commercial sale.

We may also terminate the License Agreements upon sixty (60) days’ written notice if Oncoheroes

challenges any of our licensed patents included under the License Agreements.

The License Agreements may also be terminated by either

party upon the material breach of the agreement by the other party if such breach is not cured within sixty (60) days, or in the event

that either party files for bankruptcy.

Amended and Restated

License Agreement with Liplasome and Chosa

On March 28, 2022, Allarity

Therapeutics Europe ApS (“Allarity Europe”), our wholly-owned subsidiary, entered into an amended and restated license agreement

(the “Amended License Agreement”) with LiPlasome Pharma ApS, a company organized under the laws of Denmark (“LiPlasome”),

and Chosa ApS, a company organized under the laws of Denmark (“Chosa”), regarding the development and commercialization of

LiPlaCis ® as a cancer treatment drug.

The Amended License Agreement assigned, amended and restated the original license

agreement dated February 15, 2016, as subsequently amended and restated as of January 27, 2021, by and between us and LiPlasome (the “Original

Under the Original Agreement, we were granted an exclusive license to develop and commercialize LiPlaCis ® as a

cancer treatment drug.

Pursuant to the Exclusive License Agreement dated as of June 26, 2020 (the “2020 Sublicense Agreement”)

with Smerud Medical Research International AS, a company organized under the laws of Norway (“Smerud”), we sub-licensed our

exclusive rights to LiPlaCis ® and 2X-111 (a Phase 2-stage cancer drug that is a targeted, liposomal formulation of chemotherapeutic

doxorubicin), to Smerud.

Under the Amended License Agreement, the parties agreed to terminate the 2020 Sublicense Agreement and 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, Chosa replaced Allarity Europe as the exclusive licensee to the LiPlaCis ® technology.

In addition, we also granted Chosa an exclusive, royalty-free, transferable and sublicensable license for (i) our DRP ® Companion

Diagnostics that are specific for Cisplatin or LiPlaCis ® (a liposomal formulation of Cisplatin) for the research and development of

LiPlaCis ® products, and (ii) the use of any and all know-how and intellectual property rights owned by us for Chosa’s

use of our DRP ® Companion Diagnostics that are specific for Cisplatin or LiPlaCis ® (a liposomal formulation of

Cisplatin) for the development and commercialization of LiPlaCis ® products, as contemplated in the Amended License

Development Milestone

to the Amended License Agreement, we are 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) upon the regulatory approval of a product in the United States, (ii) upon the regulatory approval of a product in any country in Europe,

including on a centralized filing basis by the EMA, (iii) upon the first achievement on a cumulative basis of net sales of a product in

the United States, and (iv) upon the first achievement on a cumulative basis of net sales of a product in any country in Europe.

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 (“Milestone Payments”).

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.

LiPlaCis Support Agreement

with Smerud, Chosa and LiPlasome

March 28, 2022, 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 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 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 2020 Sublicense Agreement as contemplated by the parties pursuant to the terms of the Support Agreement.

Notwithstanding

the provisions of Section 8.1 of the 2020 Sublicense Agreement regarding the rights relating to the ownership of certain intellectual

property (and the defined terms therein) which was agreed to survive without limitation, pursuant to the terms of the Support Agreement

and in connection with the termination of our exclusive licensee rights to LiPlaCis ® under the Amended License Agreement, on March

28, 2022, Smerud and Allarity Europe agreed to terminate the 2020 Sublicense Agreement.

However, notwithstanding the termination of the

2020 Sublicense Agreement, we are currently engaged in discussions with Smerud in connection with the further development of 2X-111.

First Amendment to License Agreement with Novartis

April 12, 2022, Allarity Therapeutics Denmark ApS (“Allarity Denmark,” or “OV-SPV2”), a subsidiary of Allarity

Therapeutics Europe ApS (“Allarity Europe”), our wholly-owned subsidiary, re-issued

a Convertible Promissory Note (the “Note”) to Novartis Pharma AG, a company organized under the laws of Switzerland (“Novartis,”

and together with Allarity Europe, the “License Parties”) in the principal amount of One Million Dollars ($1,000,000).

Note was re-issued pursuant to the First Amendment to License Agreement, with an effective date of March 30, 2022 (the “First Amendment”),

entered into by and between the License Parties, which amended the License Agreement dated April 6, 2018 (the “Original Agreement”)

previously entered into by the License Parties relating to the Compound (as defined in the Original Agreement).

The First Amendment amends

and restates Section 11.7 of the Original Agreement to add the revised Note to the list of enforceable claims in the second paragraph

of Section 11.7 making the revised Note enforceable under New York law as a legal obligation of Allarity Denmark (f/k/a OV-SPV2 ApS).

All other provisions of the Original Agreement and Note were unchanged and remain in full force and effect.

Implications of Being an Emerging Growth Company

9 unchanged sentences

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

In other words, an “emerging growth company” can delay the adoption of certain accounting standards until those

standards would otherwise apply to private companies.

We are not electing to delay such adoption of new or revised accounting standards,

and as a result, we will comply with new or revised accounting standards on the relevant dates on which adoption of such standards is

required for non-emerging growth companies.

We cannot predict if investors will find our common stock less attractive because we may rely

on these exemptions.

If some investors find our common stock less attractive as a result, there may be a less active trading market for

our common stock and our stock price may be more volatile.

We may take advantage of these reporting exemptions until we are no longer

an “emerging growth company.” We will remain an “emerging growth company” until the earliest of (i) the last day

of the fiscal year in which we have total annual gross revenues of $1.07 billion or more;

(ii) the last day of our fiscal year following

the fifth anniversary of the date of the completion of our Recapitalization Share Exchange;

(iii) the date on which we have issued more

than $1 billion in nonconvertible debt during the previous three years;

or (iv) the date on which we are deemed to be a large accelerated

filer under the rules of the SEC.

Additionally, we are a “smaller

5 unchanged sentences

We may continue to be a

smaller reporting company after the Recapitalization Share Exchange is consummated 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.

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

On April 6, 2021, we were

incorporated as Allarity Therapeutics, Inc., a Delaware corporation, for the purposes of undertaking our Recapitalization Share Exchange,

our PIPE Financing, and migrating the trading in our shares from the Nasdaq First North Growth Market:

Stockholm to Nasdaq in the U.S.

Upon the consummation of our Recapitalization Share Exchange in December 2021, we acquired substantially all of the

assets and assumed substantially all of the liabilities of our parent, Allarity Therapeutics A/S.

As a result, our parent became our predecessor

upon consummation of the Recapitalization Share Exchange.

Our parent was originally organized as Oncology Venture A/S, an Aktieselskab

organized under the laws of Denmark and changed its name to Allarity Therapeutics A/S on October 7, 2020.

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 210 Broadway, Suite 201, Cambridge, MA 02139 and our telephone number is (401) 426-4664.

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 Annual Report, and

the inclusion of our website address in this Annual Report is an inactive textual reference only.

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

2 unchanged sentences

Other trademarks, trade names and service marks

appearing in this Annual 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 Annual 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

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

10 unchanged sentences

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

We are a clinical stage biopharmaceutical

We are a clinical stage pharmaceutical

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

17 unchanged sentences

DRP ® companion diagnostics.

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

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

5 unchanged sentences

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

14 unchanged sentences

(NDA) to the U.S.

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

kinase inhibitor (TKI), on December 21, 2021, which was subsequently determined by the FDA to be not sufficiently complete to permit a

substantive review and therefore was not accepted for filing.

As discussed further below, we have requested a meeting with the FDA to

discuss the nature and extent of additional clinical data, which is likely to include one or more additional clinical trials, that will

be necessary to substantiate a complete NDA application.

Concurrently with the FDA’s conclusion on our NDA, the FDA also made a

similar determination on our application for a PMA on our companion diagnostic for dovitinib.

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.

We were founded in Denmark in 2004 by our chief scientific officer, Steen Knudsen, Ph.D., and our Senior Vice President of Information

Technologies, 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.

We completed our Recapitalization

Share Exchange and listing on Nasdaq acquiring substantially all of the assets and assuming substantially all of the

liabilities of our predecessor, Allarity Therapeutics A/S on December 20, 2021.

Our clinical and commercial development team is

advancing our pipeline of targeted oncology therapeutic candidates, all of which have previously succeeded at least though 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 lead 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 metastatic renal cell carcinoma (mRCC or kidney cancer) in patients selected by our Dovitinib-DRP ®

Food and Drug Administration (FDA) for our 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.

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 Allarity’s 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.

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 Company plans to have discussions with the FDA in the early

second quarter of 2022 to clarify a path forward for approval of this lead program.

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.

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 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

4 unchanged sentences

(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 the Dana-Farber Cancer Institute (Boston, MA USA.) together with its stenoparib-specific

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

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

18 unchanged sentences

Our focused approach to address

major unmet needs in oncology leverages our management’s significant 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 entities.

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.

We often focus our acquisition efforts on therapeutic candidates that have been the subject of clinical trials conducted by large pharmaceutical companies.

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.

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 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

4 unchanged sentences

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.

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 approach:

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 approach.

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

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 development.

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:

Our lead 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,

Numerous pan-TKIs are approved and in use for the treatment of cancers, including Sorafenib (NEXAR ® , Bayer)

and Lenvatinib (LENVIMA ® , Eisai), 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

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

In retrospective analysis of these trials, patients selected with our Dovitinib-DRP ® have an observed fifty

percent (50%) increase in median overall survival when compared to DRP ® negative patients.

We plan to seek initial market

approval for dovitinib, in the U.S.

and potentially Europe, either for the treatment of mRCC or another indication (based on FDA feedback)

using our dovitinib-specific DRP ® companion diagnostic to select and treat likely responder patients.

Subsequently, we

plan to expand approved monotherapy indications for this therapeutic candidate, to potentially one or more of breast cancer, GIST, endometrial,

and/or HCC, as well as pursue combination therapy approvals, such as dovitinib with a PD-1 inhibitor.

We believe that dovitinib, if approved,

could be broadly applicable and gain market share in the pan-TKI market as both a mono-therapy and combo-therapy product.

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.

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

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

Under the terms of the RRA, if we 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

equal to 2% of the Investor’s investment upon our failure to maintain the effectiveness of the registration statement and every

30 days thereafter.

Failure to maintain the effectiveness of the registration statement also constitutes a “triggering event”

under the Certificate of Designations for the Series A Preferred Stock that would result in the accrual and payment of a dividend and

provide the Investor the right to have its remaining Series A Preferred Stock redeemed for a premium of a minimum of 125% of the Conversion

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).

December 9, 2022, the Company and 3i, LP 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 (as defined 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 until the Company and 3i agree to terminate that definition.

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

for a bridge loan to extend the Company’s cash runaway beyond December 31, 2022, in order to provide the Company with more time

to complete the process of amending its Certificate of Incorporation to increase it authorized share capital and proposed reverse stock

split to facilitate additional capital investments (the “Bridge Loan”).

Under the Secured Note Purchase Agreement, the Company

has authorized the sale and issuance of three 3i Promissory Notes, with the first note in an aggregate principal amount of $350,000 to

be issued at closing (which was received in November 2022);

the second note in the principal amount of $1,666,640 to be issued at closing

and which represents the payment of $1,666,640 due to 3i, LP in Alternative Conversion Floor Amounts, as defined in the Certificate of

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.

As of December

31, 2022, all of the notes have been issued and are outstanding.

Each 3i Promissory Note matures on January 1, 2024, carries an interest

rate of 5% per annum, and is secured by all of the Company’s assets pursuant to the Security Agreement.

In addition, 3i, LP may

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.

The voting rights described above expired on February 28, 2023.

Modification 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

which provided that pursuant to Section 8(g) of the Certificate of Designations, the parties agreed that the Conversion Price (as defined

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) 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) 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

to be the subject of the applicable conversion of Series C Preferred Stock, by (y) the applicable Conversion Price without giving effect

to clause (x) of such definition.

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

6 unchanged sentences

to provide an additional mechanism of impeding cancer cell growth.

There are numerous 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.

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

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 — exhibits superior cell export resistance, and shows less myelotoxicity than many other approved PARP inhibitors.

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

5 unchanged sentences

than use of single biomarkers, including BRCA mutation, alone, thus potentially enabling the treatment of more patients.

Currently marketed

PARP inhibitors have generated over $2 billion of sales in the past few years, and sales are increasing as these agents are used in combination

therapy approaches.

Sales of PARP inhibitors are expected to reach $9 billion in 2026 for the treatment of ovarian cancer and pancreatic

cancer alone, according to published industry sources.

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

We are currently advancing a Phase 2 clinical trial for stenoparib for the treatment of advanced ovarian cancer at the Dana-Farber

Cancer Institute (Boston, MA USA), as well as additional 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.

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 crucially involved in forming the mitotic

spindle apparatus that ensures the proper segregation of duplicated chromosomes into daughter cells during cell division.

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.

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.

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 ®

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.

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.

one of the world’s most widely used chemotherapies.

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

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.

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.

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 is an advanced, targeted liposomal formulation of Doxorubicin, one of the world’s most widely used chemotherapies.

We exclusively

in-licensed this therapeutic candidate from 2BBB Medicines, B.V.

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 doxorubicin, 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.

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 Allarity.

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

is an advanced, targeted liposomal formulation of Doxorubicin, that remains one of the world’s most widely used chemotherapies.

We exclusively in-licensed this therapeutic candidate from 2BBB Medicines, B.V.

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),

11 unchanged sentences

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 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

5 unchanged sentences

another 27 DRP ® patent applications pending covering 2 additional cancer drugs.

We recently received allowance from the

Patent and Trademark Office (USPTO) on 3 pending applications including our Dovitinib-DRP ® , and our rolling patent

strategy allows our DRP ® patents to be listed for the drugs where they occur in the approval label.

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 product and the relevant patents.

Our Chief Executive Officer,

Carchedi, brings over 30 years of commercial experience in specialty pharmaceuticals, diagnostics, and precision medicine with

fortune 500 organizations.

He previously served as the Chief Executive Officer and President of Apexian Pharmaceuticals, Inc., an oncology

discovery, and development company, and as Chief Executive Officer and President of Raphael Pharmaceuticals, Inc.

(formerly Cornerstone

Pharmaceuticals), an oncology discovery, and development company, where he raised over $20 million in investment.

Prior to that, he served

as Senior Vice President and President, Commercial Operations for Mallinckrodt Pharmaceuticals, managing a $2 billion business with 5

operating companies.

He also served as Chief Marketing Officer for General Electric (GE) Healthcare-Molecular Diagnostics, where he was

responsible for leading worldwide marketing for GE’s $2.5 Billion Medical Diagnostics business.

Prior to joining GE Healthcare,

Carchedi held senior commercial leadership positions at Endo Pharmaceuticals, Enzon Pharmaceuticals, Johnson & Johnson, Eli Lilly

& Company, and Bristol Myers Squibb.

While at Enzon, he led the company’s exit strategy resulting in a sale to Sigma Tau Pharmaceuticals

in 2009 for over $327 million.

While at Johnson & Johnson, he led the worldwide launch of VELCADE ®

(Bortezomib), which now treats Multiple Myeloma in over 80 countries, with global sales currently at $1.5 billion.

While at Eli Lilly,

he played a key role in commercializing GEMZAR ® (Gemcitabine) and ALIMTA ®

(Pemetrexed Di-sodium), two of the leading chemotherapies on the market today, and led the development of Lilly’s oncology strategy,

which delivered $1.5 billion in annual sales.

Our clinical, senior management

team has broad expertise and a successful track record of clinically developing and commercializing new medicines and developing and exploiting

companion diagnostics to enable Personalized Medicine.

Our Chief Medical Officer, Marie Foegh, M.D., Dr.Sc., brings more than thirty years

of experience in the pharmaceutical and biotechnology industries, with a proven track record of medical leadership within clinical development

and medical affairs.

She previously served as the President of Henri Beaufour Institute, as a Medical Director for Ipsen Pharmaceuticals,

and later as Vice President of Medical Affairs, Strategy and Development, Female Health Care, at Bayer Pharmaceuticals.

Earlier in her

career, she served as Vice President of Clinical Development, at Berlex Laboratories, and as Vice President of Clinical R&D, for Agile

Therapeutics.

During her career, Marie advanced numerous therapeutic products through development and regulatory approval, including Decapeptyl

(prostate cancer);

Somatuline (gastro-pancreatic-neuroendocrine tumors and acromegaly);

Yaz (premenstrual dysphoric disorder, acne, oral

contraceptive);

Yasmin (oral contraceptive);

and Menostar, a weekly transdermal patch (osteoporosis).

She has deep expertise in clinical

development and approval of human therapeutics, including regulatory filings and relationships with the FDA and EU EMA.

Our Chief Scientific Officer,

Steen Knudsen, Ph.D., co-founded our company in 2004 and is the inventor and leading world expert in our DRP ®

platform, which is Allarity’s core companion diagnostic technology.

He is a former Professor of Systems Biology at Technical University

of Denmark and has extensive expertise in mathematics, bioinformatics, biotechnology, and systems biology of tumors.

He has developed

and patented drug-specific DRP ® biomarkers for more than 70 different cancer drugs,

validated DRP ® diagnostics in more than 35 clinical trials (retrospective) and has

played a central role in the preparation and filing of all regulatory documents with the FDA for our drug programs and DRP ®

companion diagnostics, including PMA, IND, and IDE applications.

on the relevant patents.

We strive to deliver meaningful

1 unchanged sentence

DRP ® companion diagnostics, in a personalized medicine approach.

The core elements

of our strategy include:

● Advance the U.S.

approval, and potentially European

approval, of our lead therapeutic candidate, dovitinib, for the initial mRCC indication, followed by expansion to other promising indications.

We submitted our first NDA to the FDA on December 21, 2021, for marketing approval of dovitinib for the third-line treatment

of metastatic renal cell carcinoma (mRCC) in patients selected with our Dovitinib-DRP ® companion diagnostic.

based on data from a previous Phase clinical trial by Novartis demonstrating that dovitinib is as good as (or “non-inferior”

to) Bayer’s pan-TKI Sorafenib in this patient group.

Our NDA is predicated on the use of our proprietary Dovitinib-DRP ®

companion diagnostic to select and treat patients most likely to respond to this therapeutic candidate, and we have submitted our

PMA for the use our Dovitinib-DRP ® companion diagnostic.

We believe that the DRP ® companion diagnostic

for dovitinib, if approved, will be the first complex, gene expression signature approved by the FDA as a companion diagnostic to guide

patient selection for cancer therapy.

If the FDA approves our NDA for RCC, we also intend to initiate additional clinical trials for

dovitinib, selecting patients with our Dovitinib-DRP ® companion diagnostic, for the treatment of GIST, breast cancer,

endometrial cancer, and/or liver cancer (HCC) — all indications for which the therapeutic candidate has clinical data in Phase

2 clinical trials that would support additional clinical trials — as well as potentially conduct a combination therapy clinical

trial for dovitinib together with a PD-1 inhibitor.

On 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 Allarity’s 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.

anticipates that it may be necessary to conduct a new, prospective Phase 3 study, in order to gain approval of dovitinib in the U.S.

We plan to have discussions with the FDA in early Q2 2022 to clarify a path forward for approval of this lead program.

Allarity also

intends to explore the potential for a first MAA approval for dovitinib in a first European country.

● Accelerate enrollment in, and conclusion of, our ongoing

Phase 2 clinical trials for stenoparib in ovarian cancer and IXEMPRA ® in metastatic breast cancer .

DRP ® -guided Phase 2 clinical trial of stenoparib as a treatment for ovarian cancer, being conducted at the Dana-Farber

Cancer Institute (Boston, MA USA) and other trial sites in the U.S.

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.

As the adverse effects from the COVID-19 pandemic diminish, we anticipate accelerating enrollment in our stenoparib clinical trial and

concluding the clinical trial, with data read out, sometime in second half 2022.

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 we continue to emerge from COVID-19 pandemic, we anticipate accelerating

enrollment in our IXEMPRA ® clinical trial within 2022, and concluding the clinical trial, with data read out, in 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.

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.

3 unchanged sentences

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.

Companion Diagnostics

Our Companion Diagnostics

Overview of Our DRP ® Companion

3 unchanged sentences

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 many other cancer drugs, both in clinical development and those on the market.

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

11 unchanged sentences

the clinical development of therapeutic candidates and the approved use of therapeutic products.

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:

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 ®

1 unchanged sentence

let the tumor tell us what cellular mechanisms are important to its response (or resistance) to a given cancer drug:

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.

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.

The advanced bioinformatic algorithm at the heart of our DRP ®

platform then identifies, from all mRNA and microRNA, 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.

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

2 unchanged sentences

relevant to actual clinical response of tumors (from patients) and thus reduce the background noise from our observations.

generates a putative DRP ® companion diagnostic, specific for the drug or therapeutic

candidate, which identifies a subpopulation of cancer patients most likely to respond to the drug or therapeutic candidate.

between 50 and 400 biomarkers ( i.e .

expressed genes) comprise a putative DRP ®

companion diagnostic for a specific drug or therapeutic candidate.

generates a putative DRP ® companion diagnostic, specific for the drug or therapeutic candidate, which identifies a subpopulation

of cancer patients most likely to respond to the drug or therapeutic candidate.

Typically, between 50 and 400 biomarkers ( i.e .

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 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.

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 ®

2 unchanged sentences

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:

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,

5 unchanged sentences

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 are compared to the DRP ® reference in order

to assess how closely the patient’s biomarker expression levels match the reference.

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.

The 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

the reference.

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

8 unchanged sentences

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.

inhibitors, chemotherapeutics, HDAC inhibitors, PARP inhibitors, hormone receptor inhibitors, etc.) and across both solid and hematological

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):

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.

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.

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

5 unchanged sentences

have taken place from the time of original biopsy to current treatment.

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.

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

11 unchanged sentences

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.

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

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.

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:

companion diagnostics technologies, we believe our DRP ® platform enjoys several, unique competitive advantages:

Broadly Applicable .

We believe our DRP ®

platform can successfully generate a drug-specific companion diagnostic for most cancer drug types, including:

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,

3 unchanged sentences

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.

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 Refusal to File (RTF) letter on review of this PMA, largely based on the FDA’s

issued RTF letter on the related NDA.

Company has requested a Type C meeting with the FDA to further discuss the RTFs and potential paths

forward for approval of dovitinib and its Dovitinib-DRP ®

companion diagnostic.

Separately, the stenoparib, IXEMPRA ® and LiPlaCis ®

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 the U.S.

and/or Europe.

Trusted by Clinicians .

Prominent oncologists at leading cancer centers where we are conducting

our DRP ® -guided clinical trials, including the Dana-Farber Cancer Institute (Boston, MA, U.S.A.), 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.

Priority Therapeutic Programs

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 lead therapeutic candidate,

dovitinib (formerly TKI258), is a potent and selective small molecule inhibitor targeting multiple tyrosine kinases.

It inhibits 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

As used in this section of this Annual 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.

exhibits a dual mechanism of action including anti-tumor effects via its anti-proliferative activity as well as anti-angiogenic activity.

Dovitinib is 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, PDGFR β , 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)

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.

As a result 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.

tyrosine kinases (RTKs) such as VEGFR1,2,3, FGFR1,2,3, and PDGFR β have

been shown to play an important role in tumor angiogenesis (Dvorak 2003).

VEGF 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.

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.

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.

of mTOR in anticancer drug resistance:

Role of mTOR in anticancer drug resistance:

perspectives for improved drug treatment.

1 unchanged sentence

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.

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.

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.

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.

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

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 PDGFR β , 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.

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 (PDGFR β , 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.

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

20 unchanged sentences

Study drug dose/

General Results

Advanced solid tumors P1 Dose escalation Japan

2 unchanged sentences

500 mg in SCS

MTD determined to be the 500 mg dovitinib on an oral once daily, 5 days on, 2 days off schedule

MTD determined to be the 500 mg dovitinib on an oral

once daily, 5 days on, 2 days off schedule

Advanced scirrhous gastric carcinoma

5 unchanged sentences

Primary endpoint DCR at 8 weeks:

CTKl258 as prefix

Indication/Design/

Study drug dose/

General Results

Advanced solid tumors

7 unchanged sentences

MTD defined at 125 mg daily, orally

Acute myloid leukemia P1/2 Dose escalation, multicenter

Acute myloid leukemia P1/2 Dose escalation,

50 – 600 mg qd

10 unchanged sentences

by continuous qd

MM pts had neutropenic DLTs not seen in solid tumor pts

MM pts had neutropenic DLTs not seen in solid tumor

Report combined with A2104

1 unchanged sentence

P1/2 Dose escalation, multicenter

50 mg BID, 100 mg BID, and 325 mg qd continuous dosing on 28 day cycles

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

A2103 and A2104 were discontinued due to time and dose

dependent accumulation at daily doses above 500 mg

P1/2 Dose escalation, multicenter

1 unchanged sentence

MTD reached at

Study discontinued due to no clinical benefit

Study discontinued due to no clinical

P1, single center, ADME

500 mg radiolabeled dose day 1 followed by 400 mg qd continuous dosing

500 mg radiolabeled dose day 1 followed by 400 mg qd

continuous dosing

Terminal half life about 32 hours.

Elimination via oxidative metabolism

Elimination via oxidative

Metastatic RCC

P1/2, Dose escalation and expansion, multicenter

P1/2, Dose escalation and expansion,

US, EU, Taiwan

1 unchanged sentence

5 pts at 600 mg and 82 pts

Supportive P1/2 in SCS and SCE + renal impairment (TKI258 renal impairment report – Nov 19, 2013)

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

1 unchanged sentence

(CR, PR, SD) 73.3% in the dovitinib 500 mg group per central reading

CTKl258 as prefix

Indication/Design/

Study drug dose/

General Results

P1, multicenter, crossover

3 unchanged sentences

Arm 2 – Cycle 1:

300 mg daily, crossover for test meals Cycle

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)

Food had no effect on the systemic

exposure of dovitinib (FMI capsules)

P1, multicenter, crossover

6 unchanged sentences

Bioavailability Food Effect Tablets

Food had no effect on the systemic exposure of dovitinib (FMI tablets)

P1, multicenter, drug-drug interaction (DDI)

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

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 (DDI)

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/

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 500 mg

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.

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

Excluding patients with moderate and

severe hepatic impairment from treatment with dovitinib

P1, multicenter, crossover

2 unchanged sentences

Bioequivalence established between capsules and tablets

CTKl258 as prefix

Indication/Design/

Study drug dose/

General Results

Urothelial Cancer

14 unchanged sentences

Hematological tumor toxicities differ from solid tumors

Terminated after stage 1 according to protocol

Hepatocellular carcinoma 1 st line

Terminated after stage 1 according

Hepatocellular carcinoma 1 st

P2, multicenter

3 unchanged sentences

Phase 2 randomized in SCS

Metastatic breast cancer, HER2-, HR+

P2, randomized, double blind, placebo controlled

Fulvestrant + dovitinib 500 mg qd 5 days on/2 days off vs.

Metastatic breast cancer, HER2-,

P2, randomized, double blind, placebo

Fulvestrant + dovitinib 500 mg qd 5 days on/2 days off

Fulvestrant + Placebo

3 unchanged sentences

0.406, 1,143)

Endometrial cancer with or without FGFR2 mutation

Endometrial cancer with or without

FGFR2 mutation

P2, multicenter, single arm

3 unchanged sentences

29.0% in FGFR2 wild type

Advanced RCC after failure of at least 1 VEGF and 1 mTOR targeted therapy

Advanced RCC after failure of at least 1 VEGF and 1

mTOR targeted therapy

500 mg qd X 5 days

6 unchanged sentences

DCR at 12 weeks

CTKl258 as prefix

Indication/Design/

Study drug dose/

General Results

Progressed on imatinib and sunitinib

500 mg qd X 5 days

Phase 2 Investigator initiated No CSR only a publication Kang et.

Phase 2 Investigator initiated No CSR only a publication

al., British Journal of Cancer (2013) 109, 2309 – 2315

1 unchanged sentence

We believe the clinical data

in these trials justify further clinical trials for dovitinib in GIST, endometrial 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.

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.

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 pretreated advanced RCC patients that are refractory to standard therapies.

20 patients treated in phase I with 500 mg (N = 15) or 600 mg (N = 5) dovitinib, the MTD was defined as 500 mg.

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

1 unchanged sentence

In the Phase II portion

of the study, 67 heavily pretreated 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.

Thirty-five 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 (DCR;

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

5 unchanged sentences

with metastatic RCC after failure of anti-angiogenic (VEGF- targeted and mTOR inhibitor) therapies.

Supportive data will come 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).

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

26 unchanged sentences

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.

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, 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, 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

9 unchanged sentences

Since the upper bound margin of 95% CI in the unstratified analysis

of PFS was 1.04, 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, 95% CI:

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).

5 unchanged sentences

0.779, 1.146%.

Since the upper bound of the two-sided 95% confidence interval for the hazard ratio is <1.153, the results show that

dovitinib is non-inferior to sorafenib.

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

2 unchanged sentences

to identify patients who were more likely to benefit from treatment with dovitinib in the A2302 study and thus validating the Dovitinib-DRP ® .

Hundred and thirty five dovitinib-treated patients’ renal biopsy tissue comprised the investigational arm of the “Dovitinib

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;

These results show a marginal

and non-significant improvement in median PFS for DRP ® -selected dovitinib-treated

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.)

3 unchanged sentences

DRP Study” on the other efficacy outcome measure OS, revealed a favorable outcome.

It showed a 14.95 months median OS for DRP-selected

dovitinib-treated patients versus an 11.20 months median OS for sorafenib-treated patients.

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

6 unchanged sentences

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 months median PFS for DRP ® -selected

dovitinib-treated patients versus 3.6 months 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 increased.

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

2 unchanged sentences

the adverse events observed in the prior Phase 3 trial in RCC:

Most frequently occurring AEs

by MedDRA System Organ Class and Preferred Term:

ISS 6.2B TEAEs by MedDRA SOC and PT — Pooled RCC Studies, Safety Population (>5%)

System Organ Class (1)

Preferred Term (1)

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

Sorafenib N=284

Subjects With ≥ 1 TEAE

Total Number Of TEAEs

Blood And Lymphatic System Disorders

Gastrointestinal Disorders

Abdominal Pain

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%)

89 unchanged sentences

By Preferred Term, Maximum Grade and Treatment (Safety Set)

Preferred Term

Palmar-Plantar Erythrodysaesthesia Syndrome

17 unchanged sentences

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.

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.

2 unchanged sentences

Globally, the incidence of

RCC varies widely from region to region, with the highest rates observed in Belarus, Czech Republic, and North America.

RCC varies widely from region to region, with the highest rates observed in North America.

Approximately

2 unchanged sentences

there are approximately 79,000 new cases each year and almost 14,000 deaths from RCC on an annual basis.

In the Europe, there were approximately

In Europe, there were approximately

130,000 cases of RCC and 54,000 deaths due to kidney cancer in 2020.

3 unchanged sentences

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.

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

8 unchanged sentences

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

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

7 unchanged sentences

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.

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.

tivozanib was recently approved (March 2021) as a treatment option in the third line RCC setting.

However, tivozanib was recently approved in March

2021 as a treatment option in the third-line RCC setting.

Although these newly approved

16 unchanged sentences

Numerous pan-TKIs, including

Nexavar ® (sorafenib), Sutent ®

(sunitinib), Votrient ® (pazopanib), and Lenvima ®

Nexavar ® (sorafenib), Sutent ® (sunitinib), Votrient ® (pazopanib), and Lenvima ®

(lenvatintib) are currently used in the treatment of RCC and numerous other indications.

(tivozanib) was recently approved as a third line RCC treatment, however its use in clinical practice is yet to be established.

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.

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.

Keytruda ® ).

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 ®

2 unchanged sentences

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

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

14 unchanged sentences

7.3 M HR=0.73

Trt Control/Line of treatment

March 2009 Novartis

37 unchanged sentences

21.4 M vs 16.5 M HR 0.66 p<0.0003

Trt Control/Line of treatment

Dec 2017 Exelixis

16 unchanged sentences

HR=0.53 p=0.0001

Trt Control/Line of treatment

May 2019 EMD Serono Pfizer

16 unchanged sentences

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

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.

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

5 unchanged sentences

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.

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.

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

Overview of Hepatocellular Carcinoma (HCC)

& Rationale for Targeting Multiple Kinases in HCC

Overexpression of fibroblast

growth factor receptors (FGFRs) FGFR1, FGFR2, FGFR3, or FGFR4 and corresponding FGF ligands (FGF2, FGF8, FGF17, or FGF18) have been observed

in human hepatocellular carcinoma (HCC) tumors.

HCC accounts for approximately 80% of primary liver cancer cases, the majority of which

are diagnosed at an advanced stage of disease and are not candidates for surgical interventions.

FGF2, a potent angiogenic factor in HCC,

has been shown to augment vascular endothelial growth factor (VEGF)-mediated HCC development and angiogenesis, and perhaps may evade resistance

to VEGFR modulating agents.

Sorafenib (Bayer) is a multi-kinase

inhibitor of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR).

It was the first

effective antiangiogenic therapy for advanced HCC, and remained the only approved treatment for a decade.

Lenvatinib (Eisai) became the

second approved pan-TKI for frontline treatment in HCC.

This was followed in 2017 and 2019 by two additional TKIs approved as second line

Combination therapy of an immune checkpoint inhibitor and an anti-VEGF antibody did, in 2020, replace sorafenib as first line

standard therapy.

Several studies are ongoing combining immunotherapy and a pan-TKI.

Dovitinib is a potent inhibitor

of FGFRs, VEGFRs, and PDGFRb, with anti-tumor activity mediated by a dual mechanism of action, including antiproliferative and antiangiogenic

Preliminary anti-tumor activity for dovitinib has been reported in patients with metastatic renal cell carcinoma, metastatic

melanoma, breast cancer, multiple myeloma, and acute myeloid leukemia.

Dovitinib activity has been evaluated in multiple preclinical xenograft

models in HCC.

In the sorafenib-sensitive PLC5 HCC model, dovitinib was observed to inhibit tumor growth in a dose-dependent manner.

in patient-derived HCC xenograft models, dovitinib demonstrated anti-tumor activity superior to that of sorafenib and antiangiogenic effects

that correlated with FGFR, PDGFRb, and VEGFR2 signaling pathway activation.

These data supported a prior Phase 2, open-label, multicenter,

randomized study conducted in the Asia-Pacific region evaluated the anti-cancer activity and toleration of dovitinib compared with sorafenib

in patients with advanced HCC.

In the randomized Phase 2 study,

dovitinib activity was not greater than that of sorafenib as frontline therapy in Asian-Pacific patients with advanced HCC.

median OS was similar for dovitinib and sorafenib (34.6 versus 36.7 weeks [8.0 versus 8.4 months]).

Similarly, the median TTP as determined

by the local investigator did not differ with dovitinib and sorafenib treatment in this study (17.6 versus 17.9 weeks [4.0 versus 4.1

These results are similar to those of studies evaluating other tyrosine kinase inhibitors (TKIs) versus sorafenib, although

differences in toxicity and OS have been observed.

The following graphic summarizes the design of and enrollment in that study:

We have previously observed

the ability of our Dovitinib-DRP ® companion diagnostic to correctly identify HCC patients most likely to respond to the

drug using biopsy data from the prior Phase 2 HCC trial.

Given the promising prior activity of dovitinib in HCC, and the observed ability

of our Dovitinib-DRP ® companion diagnostic to select and treat the patients most likely to respond to the drug, we are

evaluating whether to conduct a future DRP ® -guided Phase 2 clinical trial for HCC, following potential FDA approval of

dovitinib in mRCC as an initial indication.

We are also considering other potential, alternative follow-on indications, including dovitinib

in combination with Fulvestrant, for the treatment of estrogen-receptor positive (ER+) metastatic breast cancer, based on prior Phase

2 study results achieved by Novartis.

Clinical Development Plan for Dovitinib

We anticipate that this study

would be performed as an open, uncontrolled Phase II study of dovitinib in up to 30 HCC patients stable on treatment with a PD-1 inhibitor.

Patients with predicted high likelihood of responding to dovitinib using the Dovitinib-DRP ®

companion diagnostic would be included in the study.

In this study, a high likelihood of response to dovitinib will be defined as the

patient having a Dovitinib-DRP ® score of >50%.

However, this DRP ®

cutoff may be modified depending on the clinical outcome.

Once initiated, this study

would 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 dovitinib.

Patients would receive a daily dose of 500 mg dovitinib 5 days on/2 days off as tablets administered

in a 28 days cycle.

The treatment would continue until disease progression or unacceptable toxicity.

We anticipate that the clinical endpoint

will be clinical response rate and objective response rate according to RECIST.

Patients would 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 would be conducted when administration of dovitinib is stopped.

with CR, PR or SD where treatment has been stopped would continue follow-up by phone every 12 weeks until death.

Development for Additional Indications

Based on prior Phase 2 clinical

trials (conducted by Novartis) and our positive observation of the Dovitinib-DRP ®

using biopsy materials/data from such studies in endometrial cancer, in metastatic ER positive breast cancer (dovitinib in combination

with fulvestrant), and gastrointestinalstromal tumor (GIST), these three indications are near term opportunities to further develop and,

once approved, market dovitinib.

Additionally, given the commercial success of the pan-TKI Lenvima ®

(Eisai) in combination with the PD-1 inhibitor Keytruda ® (Merck), for the treatment

of numerous indications, we believe there is an opportunity to further develop and, once approved, market dovitinib in combination with

another approved PD-1 inhibitor, such as Opdivo ® (BMS).

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.

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

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).

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.

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

3 unchanged sentences

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

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.

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

4 unchanged sentences

was filed with the FDA on April 1, 2021.

On 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 Allarity’s 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.

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

2 unchanged sentences

conduct a new, prospective Phase 3 study, to gain approval of dovitinib in the U.S.

We plan to have discussions with the FDA to clarify

a path forward for approval of this lead program.

The Dovitinib-DRP ®

5 unchanged sentences

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:

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

1 unchanged sentence

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).

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 and its companion diagnostic Dovitinib-DRP ® .

However, we anticipate that the FDA will require a prospective Phase 3 clinical trial before regulatory approval of Dovitinib and its

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,

4 unchanged sentences

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 9 – 12 June 2021, and at the European Society

for Medical Oncology (ESMO) 2021 Virtual Congress held from September 16 until September 21, 2021.

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:

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.

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.

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.

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):

2 unchanged sentences

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

But the 95% confidence interval of the OS and PFS hazard ratios included those hazard ratios observed for the other cohorts

and the RCC phase III cohort.

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.

On 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 Allarity’s 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.

We believe that the primary basis for the RTF we received for our Dovitinib-DRP ® companion diagnostic

is linked to the RTF we received for our NDA for dovitinib itself.

Accordingly, we anticipate that we may gain PMA approval for our Dovitinib-DRP ®

companion diagnostic concomitant with our NDA for dovitinib, once the FDA accepts and approves the latter.

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)

11 unchanged sentences

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);

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.

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 Annual 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 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.

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

8 unchanged sentences

in vivo activity as a single agent in models of B cell lymphoma and AML.

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.

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

42 unchanged sentences

Paclitaxel in Subjects with Advanced Solid Tumors.

The first part (Phase 1) of the study started 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.

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.

data including the retrospective/prospective Stenoparib-DRP ® selection results were

presented at ASCO 2018.

final data including the retrospective/prospective Stenoparib-DRP ® selection results were presented at ASCO 2018.

The study was conducted as

10 unchanged sentences

least 1 dose of stenoparib and were included in the safety, PK, and pharmacodynamics analyses.

Twelve (12) subjects who received the 600

mg dose of stenoparib in both fed and fasted states were analyzed for food effect.

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

4 unchanged sentences

(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

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.

5 unchanged sentences

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.

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

21 unchanged sentences

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 overall median duration of treatment

for all dose groups was 57 days (range:

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 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.

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

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).

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.

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.

Overall, Grade 3 events were reported in 27 subjects (65.9%) and

the most frequently reported Grade 3 event was fatigue (n=7, 17.1%).

A single Grade 4 AE of non-treatment-related hypokalemia was reported

in a subject in the 200 mg dose group.

Overall, Grade 3 events were reported in 27 subjects (65.9%) and the most frequently reported Grade 3 event was fatigue (n=7, 17.1%).

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

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%).

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 serious events of skin rash were reported.

All but 1 event of Grade 3 erythematous rash reported

with the 600 mg dose group.

All but 1 event of Grade 3 erythematous rash reported with the 600 mg dose group.

Preliminary anti-cancer activity

8 unchanged sentences

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.

A waterfall plot of the individual responses of 35 subjects from the safety cohort is presented below:

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

6 unchanged sentences

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.

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

3 unchanged sentences

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.

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.

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 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 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.

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 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.

Secondary endpoints are CBR, PFS and OS.

is being conducted at the Dana-Farber Cancer Institute (Boston, MA, USA.) and Guy’s Hospital (London, England), in addition to other

trials sites in the U.S.

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%.

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.

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.

Stenoparib-DRP ® -selected patients commenced enrollment in June 2021.

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.

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

58 unchanged sentences

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

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

2 unchanged sentences

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.

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

2 unchanged sentences

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.

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).

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

12 unchanged sentences

in individuals with advanced PDAC with the HRD phenotype.

Development Plan for Stenoparib in

Development Plan for Stenoparib

This study would be performed

1 unchanged sentence

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.

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

2 unchanged sentences

administration of stenoparib.

Patients will receive a daily dose of 600 mg stenoparib as hard gelatin capsules administered in a 28 days

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.

12 unchanged sentences

Deb Sarker (UK).

Development for Additional Indications

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-pretreated 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-pretreated metastatic castration-resistant

prostate cancer patients selected by the Stenoparib-DRP ® companion diagnostic.

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.

Anti-tumor 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.

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.

1 unchanged sentence

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 of BRCA mutation.

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

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.

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.

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.

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

22 unchanged sentences

Ovarian only (N=3)

Responders (PR)

Non-responders (SD+PD)

DRP ® positive (top 50%)

7 unchanged sentences

All histologies (N=13)

Responders (PR)

Non-responders (SD+PD)

DRP ® positive (top 50%)

12 unchanged sentences

status considered, but was only available for 7 patients in the trial (NCT01618136), of which 6 are BRCA mutated.

Of these 6, 1 responds

Of these 6, 1 responded

to stenoparib, giving a response rate of 1/6 or 16% in the BRCA mutated population.

1 unchanged sentence

13 patients analyzed with DRP ® score.

Thus, BRCA mutation does not appear to be a

predictor of response in this small trial.

Thus, BRCA mutation does not appear to be a predictor of response in this small trial.

In sum, our retrospectively

3 unchanged sentences

Existing PARP Inhibitors and Our Opportunity

Numerous PARP inhibitors, including

Lynparza ® (olaparib), Rubraca ®

(rucaparib camsylate), Zejula ® (niraparib) and Talzenna ®

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

8 unchanged sentences

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.

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 rates, avoiding adverse events in patients that are not likely to benefit from our drug, and providing

health economics advantages.

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

rates, avoiding adverse events in patients that are not likely to benefit from our drug, and providing health economics advantages.

Furthermore, our DRP ®

1 unchanged sentence

of only assessing BRCA 1 and 2 mutation status in order to select and treat patients.

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.

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

(IXEMPRA ® ) is a semisynthetic derivative of epothilone B, with improved in vitro metabolic

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 Annual 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

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.

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

11 unchanged sentences

and the metabolite profile was similar among species including humans;

(e) metabolized by CYP3A4/5;

I metabolized by CYP3A4/5;

(f) cleared primarily via oxidative

2 unchanged sentences

Pre-Clinical Studies

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).

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

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

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

93 unchanged sentences

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 57 mg/m 2 .

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

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 Phase 1/2 clinical trial

(CA163031) evaluating ixabepilone in combination with capecitabine for the treatment of metastatic breast cancer (MBC), common toxicities

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.

5 unchanged sentences

discontinuation of ixabepilone.

In a large, international Phase

3 clinical trial (CA16304612) in patients with taxane-resistant and anthracycline-pretreated 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

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.

7 unchanged sentences

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.

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

2 unchanged sentences

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.

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

7 unchanged sentences

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.

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

patients, is being conducted at numerous sites in Europe, including Belgium, England, Denmark, Finland, Poland and Germany.

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 the U.S.

patients, is being conducted at numerous sites in Europe, including Belgium, England, Finland, Poland and Germany.

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).

Dose reduction is required in certain patients with elevated AST, ALT, or bilirubin.

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 ® but not selected with the putative DRP ® companion diagnostic for the drug.

Since the Phase 2 clinical trials currently are ongoing, data from these trials is not yet available to report.

have entered into a cost sharing arrangement with Smerud Medical 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.

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 ®

but not selected with the putative DRP ® companion diagnostic for the drug.

Since the Phase 2 clinical trials currently

are ongoing, data from these trials is not yet available to report.

We have entered into a cost sharing arrangement with Smerud Medical

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.

U.S., breast cancer has the highest prevalence among all cancers.

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.

In the U.S., breast cancer has the highest prevalence among all cancers.

The Surveillance, Epidemiology, and End Results (“SEER”)

19 unchanged sentences

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 ® ).

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 ® ).

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.

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.

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.

as third- or fourth-line treatment of metastatic breast cancer in the following settings:

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, Denmark, 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.

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

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

mechlorethamine, doxorubicin, vincristine, bleomycin, etoposide, dacarbazine, brentuximab, cisplatin, ifosfamide, methotrexate,

Leukemias, lymphomas, myeloma, breast, lung, head &

neck, sarcomas, Wilms’ tumor, neuroblastoma, retinoblastoma, medulloblastoma,

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

doxorubicin, carboplatin mechlorethamine, vinblastine, bleomycin, etoposide, cyclophosphamide, procarbazine, topotecan, dactinomycin,

leucovorin, actinomycin D

Monotherapy, doxorubicin, carboplatin mechlorethamine, vinblastine, bleomycin, etoposide, cyclophosphamide, procarbazine, topotecan, dactinomycin, leucovorin, actinomycin D

ALL, CML, melanoma, breast

1 unchanged sentence

Monotherapy, cisplatin

NSCLC, Hodgkin’s disease, non-Hodgkin lymphoma,

rhabdomyosarcoma, Wilm’s tumor, neuroblastoma

NSCLC, Hodgkin’s disease, non-Hodgkin lymphoma, rhabdomyosarcoma, Wilm’s tumor, neuroblastoma

25 mg/m 2 – 30 mg/m 2

6 unchanged sentences

100 mg/m 2 – 210 mg/m 2

cisplatin, doxorubicin

Monotherapy, cisplatin, doxorubicin

Breast, lung, prostate, gastric, head & neck

75 mg/m 2 – 100 mg/m 2

cyclophosphamide, cisplatin, 5-fluorouracil

Monotherapy, cyclophosphamide, cisplatin, 5-fluorouracil

Nab-Paclitaxel

1 unchanged sentence

100 mg/m 2 – 260 mg/m 2

carboplatin, gemcitabine

Monotherapy, carboplatin, gemcitabine

20 mg/m 2 – 25 mg/m 2

agents first approved by FDA(*), EMA(**) or in other countries (***).

Anti-tubulin agents first

approved by FDA (*), EMA (**) or in other countries (***).

acute lymphoblastic leukemia;

1 unchanged sentence

non-small-cell lung carcinoma

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

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

1 unchanged sentence

neutropenia and neurotoxicity, and the development of tumor resistance to the drugs after long-term use.

For example, among taxane-naıve

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.

Taxane resistance rates of up to 55% in anthracycline-pretreated patients and up to one-third in anthracycline-naıve patients have been reported.

Second-line, the same spectrum of outcomes can

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.

Therapeutic Programs

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.

Taxane resistance rates of up to 55% in anthracycline-pre-treated patients

and up to one-third in anthraIne-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)

(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 Annual 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

FDA 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

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).

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.

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 ®

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,

13 unchanged sentences

– 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 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.

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.

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.

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 cancer 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 Annual 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 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 2X-111 ® or our putative Doxorubicin-DRP ® companion diagnostic.

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.

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.

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.

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

or our observations that our therapeutic candidate 2X-111 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 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.

The following graphs represent some of the preclinical observations:

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.

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.

(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.

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 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.

The study was performed in two phases:

a dose escalation phase following a standard “3+3”

“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).

(84) 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:

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):

Patients who received at least one dose of 2X-111 were evaluable for safety analysis.

to Treat (ITT):

All patients in the SAF 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.

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.

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.

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.

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.

Stable or decreasing dosages of steroids (e.g.

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.

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.

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.

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.

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.

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.

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 tolerated, the infusion was then completed over the next hour for

a total infusion time of 90 minutes.

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.

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.

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.

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 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.

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.

Each treatment cycle consisted of 21 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:

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:

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.

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:

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:

Characteristic

1 unchanged sentence

Median (min, max)

82.0 (51, 126

Median (min, max)

Surface Area (kg/m 2 )

172 (153, 197

170 (147, 191

Body Surface Area (kg/m 2 )

Median (min, max)

1.873 (1.34, 2.29

2.038 (1.60, 2.59

Ethnicity (N)

Caucasian/white (%)

receptor on BC (N)

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.

Tumour Type (N)

Her2/Neu on BC (N)

Progesterone receptor on BC (N)

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.

The first cycle of drug was not initiated until baseline MRI has been performed.

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:

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

groups in mg/m 2

Dose groups in mg/m 2

Malignant Glioma

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.

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.

The following table summarizes those results:

groups in mg/m 2 > = 40 mg

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 .

Dose 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 .

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

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

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 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 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 from TMZ.

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.

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

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.

However, the treatment options for recurrent GBM are limited and the prognosis is poor.

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

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

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.

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.

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.

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.

Companion Diagnostic for 2X-111

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

8 unchanged sentences

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).

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).

A total of 140 patients received epirubicin and were included in the analysis.

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.

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

1 unchanged sentence

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

(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).

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

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.

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-Pretreated 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.

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%.

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.

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.

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.

, Gene 644 80-86)

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 infringing

valid and enforceable patents and proprietary rights of others, 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 issued DRP ® 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

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

4 unchanged sentences

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 is difficult to reverse engineer.

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.

As of March 28, 2022, our company-owned

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:

3 unchanged sentences

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,

Mexico, Egypt, Saudi Arabia 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

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.

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).

International 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 controlled) U.S.

and foreign patent

applications will vary in accordance with the laws of each jurisdiction but is typically

20 years from the earliest non-provisional application filing date.

Expiration dates

for certain patents covering our portfolio assets ranges between 2028 and 2032.

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 controlled) 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.

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.

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 and product protection well after the core product

patents (e.g.

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.

composition-of-matter) have expired.

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.

(“Eisai”) that protect stenoparib compositions and methods of its use for

Our in-licensed patent on the composition of matter for dovitinib expired on September 11, 2021.

dovitinib patent portfolio, which includes pending 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.

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), which correspond to

International Patent Application No.

PCT/EP2011/060949, protect pharmaceutical dovitinib

compositions and methods for producing pharmaceutical compositions containing dovitinib.

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.

granted in the United States (US 8,741,903), Europe (EP 2558095), and Australia (AU 2011239999),

which correspond to International Patent 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.

have patent rights covering the use of the DRP ® technology in conjunction

with dovitinib in the United States (US 10,835,531).

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.

be pursued in key foreign jurisdictions, including Australia, Canada, China, Europe, India,

Japan, Brazil, Mexico, Egypt, and Saudi Arabia, in connection with International Patent Application

PCT/EP2020/066724.

National applications were filed in November 2021.

This portfolio

is scheduled to expire in 2040.

stenoparib patent portfolio, which includes pending 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.

corresponding to International Patent Application No.

PCT/US2008/078606 that are In-licensed

from Eisai include composition of matter claims directed to genera and species encompassing

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.

are pursuing patent protection for the use of our DRP ® technology in conjunction

with stenoparib via International Patent Application No.

PCT/EP2019/062508, which has been

filed in the United States, Australia, Canada, China, Europe, India, and Japan.

This portfolio

is scheduled to expire in 2039.

ixabepilone patent portfolio, which is owned by us, is based on protecting our DRP ® technology in the United States and

in key foreign jurisdictions.

Patent applications corresponding to International Patent Application No.

PCT/EP2021/052132, which seeks

to cover the use of the DRP ® technology in conjunction with ixabepilone, will be pursued in the United States and in key

foreign jurisdictions, including Australia, Canada, China, Europe, India, Japan, Brazil, Mexico, Egypt, and Saudi Arabia.

National applications

will be filed starting in July 2022.

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.

We do not own or control any patents relating to

ixabepilone itself in the EU market, where such patents have previously expired

2X-111 patent portfolio, which includes U.S.

and foreign patents, is positioned to protect aspects of our business in the United States

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).

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.

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.

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.

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 issue and in force until December 2025;

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.

own exclusive, global rights to the use of our DRP ® technology in conjunction with doxorubicin, which is the active therapeutic ingredient

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.

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.

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, and

could affect the value of such intellectual property and the business.

With respect to our company-owned (or controlled) intellectual

property, we cannot guarantee that the patent applications we are currently pursuing or may file in the future will issue as patents

in any particular jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors.

Our competitors may independently develop similar investigational products or technologies that are outside the scope of the rights granted

under any company-owned (or controlled) patents that may issue.

We cannot be sure that any patents granted to us will be commercially

useful in protecting our products or their methods of use or manufacture.

Moreover, even issued patents do not guarantee us the right

to commercialize our products.

For example, third parties may have blocking patents that could be used to prevent us from commercializing

or manufacturing our investigational products and/or our DRP ® companion diagnostics.

of the extensive time required for development, testing and regulatory review of an investigational product, it is possible that, before

a product can be commercialized, any patent protection for such product may expire or remain in force for only a short period following

commercialization, thereby reducing the commercial advantage the patent provides.

In the U.S., the term of a patent covering an FDA-approved

product may, in certain cases, be eligible for a patent term extension under the Hatch-Waxman Act as compensation for the loss of patent

term during the FDA regulatory review process.

The period of extension may be up to five years, but cannot extend the remaining term

of a patent beyond a total of 14 years from the date of product approval.

Only one patent among those eligible for an extension

may be extended and the amount of available extension to any PTE-eligible patent depends on a variety of factors, including the date

on which the patent issues and certain dates related to the regulatory review period.

Possible extensions may be available in Europe

and in certain other jurisdictions to extend the term of a patent that covers an approved product.

While we intend to seek patent term

extensions in any jurisdictions where they are available to us, there is no guarantee that the applicable authorities, including the

FDA or the USPTO, will agree with our assessment of whether such extensions should be granted, and even if granted, the length of such

cannot be sure that any patents will issue from any pending or future company-owned (or controlled) patent applications.

Even if patents

do issue, we cannot be sure that the claims of these patents will be held valid or enforceable by a court of law or governmental agency,

will provide us with any significant protection against competitive products, or will afford us a commercial advantage over competitive

might not have been the first to file patent applications for the inventions covered by our

pending patent applications and any patents that issue therefrom;

may independently develop similar or alternative technologies without infringing our intellectual

property rights;

or all of our pending patent applications may not result in issued patents or the claims

that issue may be narrow in scope and not provide us with a competitive advantage;

patents that issue from any of our pending patent applications may be challenged by a third-party

and invalidated;

patents that issue from our pending patent applications may be subject to post-grant proceedings,

oppositions or other administrative or court proceedings that may result in a reduction in

their scope or their loss altogether;

may not develop proprietary technologies or investigational products that are patentable;

patents of others may prevent us from discovering, developing or commercializing our investigational

defense and prosecution of intellectual property infringement suits, post-grant proceedings, oppositions and related legal and administrative

proceedings are costly, time-consuming to pursue and divert resources.

The outcome of these types of proceedings is uncertain and could

significantly harm our business.

development of our investigational products and the commercialization of any resulting drugs may be impacted by patents of other companies

or by companies engaged in the development of competitive programs or those with significantly greater resources.

This could result in

the expenditure of significant legal fees and management resources.

also rely on certain trade secrets to protect our technology and therapeutic candidates, especially where we do not believe patent protection

is appropriate or obtainable, or where maintaining such technology as a trade secret provides us greater competitive advantage than obtaining

a patent would.

However, trade secrets are often difficult to protect, especially outside of the U.S.

While we believe that we use reasonable

efforts to protect our trade secrets, our employees, consultants, contractors, partners and other advisors may unintentionally or willfully

disclose our trade secrets to others, including competitors.

Enforcing a claim that a third-party illegally disclosed, obtained or is

using our trade secrets would be expensive and time-consuming, and the outcome would be unpredictable.

Even if we are able to maintain

our trade secrets as confidential, our competitors may independently develop information that is equivalent or similar to our trade secrets.

Agreement with Novartis Pharma for Dovitinib

On April 6, 2018, we 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, we paid Novartis a one-time, non-refundable,

non-creditable 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.

As part 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 “Promissory Note”).

The 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 promissory

note was issued by Allarity Therapeutics Denmark ApS, a wholly owned special purpose vehicle of our subsidiary Allarity Therapeutics Europe

ApS, the licensee under the license agreement.

In the event that there is a change of control, as defined under the Promissory Note, of

Allarity Therapeutics Europe ApS, Novartis would be entitled to a payment equal to 5% of the first $30 million we receive in connection

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 Therapeutics Denmark ApS 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 Promissory Note into 3% of Allarity Therapeutics Denmark ApS outstanding equity securities immediately before the IPO.

Milestone Payments

Pursuant to the agreement, we have 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;

(iii) upon submission of the first NDA with the FDA;

(iv) submission of an 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 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 million.

As of December 31, 2021 we have accrued a $5 million royalty payment due to Novartis as a current liability.

addition to the milestone payments described above, we have agreed to pay Novartis royalties based on annual incremental sales of product

derived from dovitinib in an amount between five percent (5%) and ten percent (10%) of annual sales of between $0 and $250 million, between

six percent (6%) and thirteen percent (13%) of annual sales between $250 million and $500 million, between seven percent (7%) and thirteen

percent (13%) of annual sales between $500 million and $750 million, and between thirteen percent (13%) and fifteen percent (15%) of

annual sales in excess of $750 million.

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 ten (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 us 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.

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, coronaviruses)

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.

(“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;

(ii) dosing of the first patient in the first Phase 3 clinical trial;

(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

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;

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

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

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.

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

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