What changed in this filing

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Item 1. Business

2021-03-26 compared with 2020-03-25 · 519 added, 373 removed, 106 unchanged (89% of the section changed)

Biotechnology Holdings, Inc., a Delaware corporation, including its wholly-owned Delaware subsidiary, Lixte Biotechnology, Inc.

(collectively, the “Company”), is a drug discovery company that uses biomarker technology to identify enzyme targets

associated with serious common diseases and then designs novel compounds to attack those targets.

The Company’s product

pipeline is primarily focused on inhibitors of protein phosphatases, used alone and in combination with cytotoxic agents and/or

x-ray and immune checkpoint blockers, and encompasses two major categories of compounds at various stages of pre-clinical and

clinical development that the Company believes have broad therapeutic potential not only for cancer but also for other debilitating

and life-threatening diseases.

Company’s activities are subject to significant risks and uncertainties, including the need for additional capital, as described

The Company has not yet commenced any revenue-generating operations, does not have positive cash flows from operations,

and is dependent on periodic infusions of equity capital to fund its operating requirements.

are a drug discovery company that uses biomarker technology to identify enzyme targets associated with serious common diseases

and then designs novel compounds to attack those targets.

Our product pipeline is primarily focused on inhibitors of protein phosphatases,

used alone and in combination with cytotoxic agents and/or x-ray and immune checkpoint blockers, and encompasses two major categories

of compounds at various stages of pre-clinical and clinical development that we believe have broad therapeutic potential not only

for cancer but also for other debilitating and life-threatening diseases.

have developed two series of pharmacologically active drugs, the LB-100 series and the LB-200 series.

We believe that the mechanism

by which compounds of the LB-100 series affect cancer cell growth is different from cancer agents currently approved for clinical

Lead compounds from each series have activity against a broad spectrum of common and rarer human cancers in cell culture

In addition, compounds from both series have anti-cancer activity in animal models of glioblastoma multiforme, neuroblastoma,

and medulloblastoma, all cancers of neural tissue.

Lead compounds of the LB-100 series also have activity against melanoma, breast

cancer and sarcoma in animal models and enhance the effectiveness of commonly used anti-cancer drugs in these model systems.

enhancement of anti-cancer activity of these anti-cancer drugs occurs at doses of LB-100 that do not significantly increase toxicity

It is therefore hoped that, when combined with standard anti-cancer regimens against many tumor types, our compounds

will improve therapeutic benefit without enhancing toxicity in humans.

activities are subject to significant risks and uncertainties, including the need for additional capital, as described below.

We have not yet commenced any revenue-generating operations, do not have positive cash flows from operations, and are dependent

on periodic infusions of equity capital to fund our operating requirements.

Clinical Trial Activities

Company’s primary focus is developing new treatments for human cancers for which better therapies are urgently needed.

Company’s drug discovery process is based on discerning clues to potential new targets for disease treatments reported in

the increasingly large body of literature identifying the molecular variants which characterize human cancers and other non-cancer

The Company designs drugs for which there are existing data suggesting that they may affect the altered pathways of

the cancer cell and may be given safely to humans.

The Company seeks to rapidly arrive at patentable structures through analysis

of the literature rather than screening of thousands of structures for activity against a particular biochemical pathway.

primary focus is developing new treatments for human cancers for which better therapies are urgently needed.

drug discovery process is based on discerning clues to potential new targets for disease treatments reported in the increasingly

large body of literature identifying the molecular variants which characterize human cancers and other non-cancer disorders.

design drugs for which there are existing data suggesting that they may affect the altered pathways of the cancer cell and may

be given safely to humans.

We seek to rapidly arrive at patentable structures through analysis of the literature rather than screening

of thousands of structures for activity against a particular biochemical pathway.

approach has led to the development of two classes of drugs for the treatment of cancer, consisting of protein phosphatase inhibitors

(PTase-i), designated by the Company as the LB-100 series of compounds, and histone deacetylase inhibitors (HDACi), designated

by the Company as the LB-200 series of compounds.

(PTase-i), designated by us as the LB-100 series of compounds, and histone deacetylase inhibitors (HDACi), designated by us as

the LB-200 series of compounds.

LB-100 series consists of novel structures which have the potential to be first in their class and may be useful in the treatment

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Gaucher’s disease, in addition to cancer and neurodegenerative diseases.

Company has demonstrated that lead compounds of both the LB-100 series and the LB-200 are active against a broad spectrum of human

cancers in cell culture and against several types of human cancers in animal models.

The research on these compounds was initiated

in 2006 under a Cooperative Research and Development Agreement (“CRADA”) with the National Institute of Neurologic

Disorders and Stroke (“NINDS”) of the National Institutes of Health (“NIH”) dated March 22, 2006 that

was subsequently extended through a series of amendments until it terminated on April 1, 2013.

have demonstrated that lead compounds of both the LB-100 series and the LB-200 are active against a broad spectrum of human cancers

in cell culture and against several types of human cancers in animal models.

The research on these compounds was initiated in

2006 under a Cooperative Research and Development Agreement or CRADA with the National Institute of Neurologic Disorders and Stroke

or NINDS of the National Institutes of Health or NIH dated March 22, 2006 that was subsequently extended through a series of amendments

until it terminated on April 1, 2013.

treatment of brain tumors depends upon the ability of compounds to penetrate a physiological barrier known as the “blood-brain

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Because there is no certainty

that the Company’s compounds will be active against tumors confined to the brain, the LB-100 compounds have been studied

against a variety of common and rare cancer types and have been shown to potentiate the activity of standard anti-cancer drugs

in animal models of breast and pancreatic cancer, melanoma, pheochromcytomas and sarcomas.

Because the LB-100 compounds appear

to exert their ability to improve the effectiveness of different forms of chemotherapy and radiation therapy by inhibiting a process

upon which most, if not all, cancer cell types depend on to survive treatment, the Company believes the LB-100 series of compounds

may be useful against most, if not all, cancer types.

that our compounds will be active against tumors confined to the brain, the LB-100 compounds have been studied against a variety

of common and rare cancer types and have been shown to potentiate the activity of standard anti-cancer drugs in animal models

of breast and pancreatic cancer, melanoma, pheochromocytomas and sarcomas.

Because the LB-100 compounds appear to exert their

ability to improve the effectiveness of different forms of chemotherapy and radiation therapy by inhibiting a process upon which

most, if not all, cancer cell types depend on to survive treatment, we believe the LB-100 series of compounds may be useful against

most, if not all, cancer types.

LB-200 series consists of histone deacetylase inhibitors (HDACi).

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type, and at least two companies have HDACi approved for clinical use, in both cases for the treatment of a type of lymphoma.

Despite this significant competition, the Company has demonstrated that its HDACi have broad activity against many cancer types,

has neuroprotective activity, and has anti-fungal activity.

Despite this significant competition, we have demonstrated that our HDACi have broad activity against many cancer types, have

neuroprotective activity, and have anti-fungal activity.

In addition, these compounds have low toxicity.

LB-200 has not yet

advanced to the clinical stage and would require additional capital to fund further development.

Accordingly, because of the Company’s

focus on the clinical development of LB-100 and analogs for cancer therapy as described below in more detail, the Company has

decided not to actively pursue the pre-clinical development of its LB-200 series of compounds at this time.

At this time, the

Company intends to only maintain its composition of matter patents for LB-200.

LB-200 has not yet advanced

to the clinical stage and would require additional capital to fund further development.

Accordingly, because of our focus on the

clinical development of LB-100 and analogs for cancer therapy as described below in more detail, we have decided not to actively

pursue the pre-clinical development of our LB-200 series of compounds at this time.

At this time, we intend to only maintain our

composition of matter patents for LB-200.

Collaborations

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by a novel mechanism and is the first of its type to be evaluated so broadly in multiple animal models of cancer and now in human

LB-100 is one a series of serine/threonine phosphatase (s/t ptase) inhibitors designed by the Company.

The s/t ptases

are ubiquitous enzymes that regulate many cell signaling networks important to cell growth, division and death.

The s/t ptases

have long been appreciated as potentially important targets for anti-cancer drugs.

However, because of the multi- functionality

of these enzymes, it had been widely held that pharmacologic inhibitors of s/t ptases would be too toxic to allow their development

as anti-cancer treatments, but the Company has shown that this is not the case.

LB-100 was well tolerated at doses associated

with objective regression (significant tumor shrinkage) and/or the arresting of tumor progression in patients with progressive

LB-100 is one of a series of serine/threonine phosphatase (s/t ptase) inhibitors designed by us.

The s/t ptases are ubiquitous

enzymes that regulate many cell signaling networks important to cell growth, division and death.

The s/t ptases have long been

appreciated as potentially important targets for anti-cancer drugs.

However, because of the multi- functionality of these enzymes,

it had been widely held that pharmacologic inhibitors of s/t ptases would be too toxic to allow their development as anti-cancer

treatments, but we have shown that this is not the case.

LB-100 was well-tolerated at doses associated with objective regression

(significant tumor shrinkage) and/or the arresting of tumor progression in patients with progressive cancers.

studies showed that LB-100 itself inhibits a spectrum of human cancers and that combined with standard cytotoxic drugs and/or

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of cancer immunotherapy.

Company completed a Phase 1 clinical trial of its lead anti-cancer compound LB-100 to evaluate its safety that showed it is associated

with antitumor activity in humans at doses that are readily tolerable.

Responses included objective regression (tumor shrinkage)

lasting for 11 months of a pancreatic cancer and cessation of growth (stabilization of disease) for 4 months or more of 9 other

progressive solid tumors out of 20 patients who had measurable disease.

As Phase 1 clinical trials are fundamentally designed

to determine safety of a new compound in humans, the Company was encouraged by these results.

The next step is to demonstrate

in Phase 2 clinical trials the efficacy of LB-100 in one or more specific tumor types, against which the compound has well documented

activity in pre-clinical models.

Company has entered into the following clinical studies during the years ended December 31, 2018 and 2019:

completed a Phase 1 clinical trial of LB-100 to evaluate its safety that showed it is associated with antitumor activity in humans

at doses that are readily tolerable.

Responses included objective regression (tumor shrinkage) lasting for 11 months of a pancreatic

cancer and cessation of growth (stabilization of disease) for 4 months or more of 9 other progressive solid tumors out of 20 patients

who had measurable disease.

As Phase 1 clinical trials are fundamentally designed to determine safety of a new compound in humans,

we were encouraged by these results.

The next step is to demonstrate in Phase 2 clinical trials the efficacy of LB-100 in one

or more specific tumor types, against which the compound has well documented activity in pre-clinical models.

Trial Agreements

Cancer Center Clinical Trial Research Agreement

August 20, 2018, the Company and the Moffitt Cancer Center and Research Institute Hospital Inc., Tampa, Florida (“Moffitt”)

entered into a Clinical Trial Research Agreement (the “Clinical Trial Research Agreement”) effective for a term of

five years, unless terminated earlier by the Company pursuant to 30 days written notice.

Pursuant to the Clinical Trial Research

Agreement, Moffitt agreed to conduct and manage a Phase 1b/2 clinical trial to evaluate the therapeutic benefit of the Company’s

lead anti-cancer clinical compound LB-100 to be administered intravenously in patients with low or intermediate-1 risk myelodysplastic

syndrome (“MDS”).

November 2018, the Company received approval from the U.S.

Food and Drug Administration (“FDA”) for its Investigation

New Drug (“IND”) Application to conduct a Phase 1b/2 clinical trial to evaluate the therapeutic benefit of LB-100

in patients with low and intermediate-1 risk MDS who have failed or are intolerant of standard treatment.

This clinical trial

began in April 2019 and the first patient was entered into the clinical trial in July 2019.

The clinical trial is expected to

be completed over a period of two years, with final analysis and reporting expected within three years.

This Phase 1b/2 clinical

trial utilizes LB-100 as a single agent in the treatment of patients with del(5q) myelodysplastic syndrome (del5qMDS) failing

first line therapy.

The bone marrow cells of these patients are deficient in PP2A by virtue of an acquired mutation and are especially

vulnerable to further inhibition of PP2A by LB-100.

August 20, 2018, we entered into a Clinical Trial Research Agreement with the Moffitt Cancer Center and Research Institute Hospital

Inc., Tampa, Florida, effective for a term of five years, unless terminated earlier by us pursuant to 30 days written notice.

Pursuant to the Clinical Trial Research Agreement, Moffitt agreed to conduct and manage a Phase 1b/2 clinical trial to evaluate

the therapeutic benefit of our lead anti-cancer clinical compound LB-100 to be administered intravenously in patients with low

or intermediate-1 risk myelodysplastic syndrome (MDS).

November 2018, we received approval from the FDA for our Investigational New Drug Application to conduct a Phase 1b/2 clinical

trial to evaluate the therapeutic benefit of LB-100 in patients with low and intermediate-1 risk MDS who have failed or are intolerant

of standard treatment.

Patients with MDS, although usually older, are generally well except for severe anemia requiring frequent

blood transfusions.

This Phase 1b/2 clinical trial utilizes LB-100 as a single agent in the treatment of patients with low and

intermediate-1 risk MDS, including patients with del(5q) myelodysplastic syndrome (del5qMDS) failing first line therapy.

marrow cells of patients with del5qMDS are deficient in PP2A by virtue of an acquired mutation and are especially vulnerable to

further inhibition of PP2A by LB-100.

The clinical trial began at a single site in April 2019 and the first patient was entered

into the clinical trial in July 2019.

A total enrollment of 41 patients is planned.

An interim analysis will be done after the

first 21 patients are entered.

If there are 3 or more responders but fewer than 7, an additional 20 patients will be entered.

If at any point there are 7 or more responders, this will be sufficient evidence to support continued development of LB-100 for

the treatment of low and intermediate-1 risk MDS.

Recruitment has been slow and the Covid-19 pandemic has further reduced recruitment

of patients into the protocol.

At the current rate of accrual, the trial would be completed over a period of four years from its

initiation, with the final analysis and reporting expected by July 2023.

However, with additional funds, our objective would be

to add two additional MDS centers to the Phase 2 portion of the study to accelerate patient accrual, with the goal of an earlier

reporting date.

Sarcoma Group Collaboration Agreement

as of July 31, 2019, the Company entered into a Collaboration Agreement for an Investigator-Initiated Clinical Trial with the

Spanish Sarcoma Group (Grupo Espanol de Investigacion en Sarcomas or “GEIS”), Madrid, Spain, to carry out a clinical

trial entitled “Randomized phase I/II trial of LB-100 plus doxorubicin vs.

doxorubicin alone in first line of advanced soft

tissue sarcoma”.

The purpose of this clinical trial is to obtain information about the efficacy and safety of the Company’s

lead anti-cancer clinical compound LB-100 combined with doxorubicin in soft tissue sarcomas.

Doxorubicin is the global standard

for initial treatment of advanced soft tissue sarcomas (ASTA).

Doxorubicin alone has been the mainstay of first line treatment

of ASTS for over 40 years, with little therapeutic gain from adding cytotoxic compounds to or substituting other cytotoxic compounds

for doxorubicin.

In animal models, LB-100 consistently enhances the antitumor activity of doxorubicin without apparent increases

GEIS has a network of referral centers in Span and across Europe that have an impressive track record of efficiently

conducting innovative studies in ASTS.

The Company has agreed to provide GEIS with a supply of LB-100 to be utilized in the conduct

of this clinical trial, as well as to provide funding for the clinical trial.

The goal is to enter the first patient into this

clinical trial during the quarter ending June 30, 2020, with approximately 170 patients to be subsequently enrolled over a period

of two years.

The Company estimates that this clinical trial will be completed and results will be published by June 30, 2023.

The original start date for patient entry was delayed due to longer than expected processing of formal approval of importation

of LB-100 into the European Union.

This approval was originally expected to be received in the quarter ended September 30, 2019,

but was delayed and is now expected to be received during the quarter ending June 30, 2020.

of July 31, 2019, we entered into a Collaboration Agreement for an Investigator-Initiated Clinical Trial with the Spanish Sarcoma

Group (Grupo Español de Investigación en Sarcomas or “GEIS”), Madrid, Spain, to carry out a study entitled

“Randomized phase I/II trial of LB-100 plus doxorubicin vs.

doxorubicin alone in first line of advanced soft tissue sarcoma”.

The purpose of this clinical trial is to obtain information about the efficacy and safety of LB-100 combined with doxorubicin

in soft tissue sarcomas.

Doxorubicin is the global standard for initial treatment of advanced soft tissue sarcomas (“ASTS”).

Doxorubicin alone has been the mainstay of first line treatment of ASTS for over 40 years, with little therapeutic gain from adding

cytotoxic compounds to or substituting other cytotoxic compounds for doxorubicin.

In animal models, LB-100 consistently enhances

the anti-tumor activity of doxorubicin without apparent increases in toxicity.

has a network of referral centers in Spain and across Europe that have an impressive track record of efficiently conducting innovative

studies in ASTS.

We agreed to provide GEIS with a supply of LB-100 to be utilized in the conduct of this clinical trial, as well

as to provide funding for the clinical trial.

The goal was to enter the first patient during the quarter ending December 31, 2020,

with approximately 150 patients to be enrolled over two years.

Advanced sarcoma is a very aggressive disease.

The design of the

study assumes a median progression free survival (PFS, no evidence of disease progression or death from any cause) of 4.5 months

in the doxorubicin arm and an alternative median PFS of 7.5 months in the doxorubicin plus LB-100 arm to demonstrate a statistically

significant decrease in relative risk of progression or death by adding LB-100.

There is a planned interim analysis of the primary

endpoint when about half of the 102 events required for final analysis is reached.

order to manufacture a new inventory supply of LB-100 for the GEIS clinical trial, the Company has engaged a number of vendors

to carry out the multiple tasks needed to make and gain approval of a new clinical product for investigational study in Spain.

These tasks include the synthesis under good manufacturing practices (GMP) of the active pharmacologic ingredient (API), with

documentation of each of the steps involved by an independent auditor.

The API is then transferred to a vendor that prepares the

clinical drug product (DP), also under GMP conditions documented by an independent auditor.

The DP is then sent to a vendor to

test for purity and sterility, provide appropriate labels, store the drug, and distribute the drug to the clinical centers for

use in the clinical trials.

A formal application documenting all steps taken to prepare the DP for clinical use must be submitted

to the appropriate regulatory authorities for review and approval before being used in a clinical trial.

Company estimates that this program to provide new inventory of the DP for the Spanish sarcoma study, and potentially for subsequent

multiple trials within the European Union, will cost from $600,000 and $700,000.

The Company’s remaining aggregate commitments

under this program, less amounts previously paid to date, totaled approximately $300,000 as of December 31, 2020, which are expected

to be incurred through June 30, 2021.

had previously expected that this clinical trial would commence during the quarter ended June 30, 2020.

However, during July 2020,

the Spanish regulatory authority advised us that although it had approved the scientific and ethical basis of the protocol, it

required that we manufacture new inventory of LB-100 under current Spanish pharmaceutical manufacturing standards.

These regulations

were adopted subsequent to the production of our existing LB-100 inventory.

We are in the process of obtaining approval from the

European Union regulatory authorities for new inventory of LB-100.

Accordingly, the clinical trial is now estimated to begin during

the quarter ending September 30, 2021 and to be completed by the quarter ending September 30, 2024.

The interim analysis is expected

in June 2023 and could indicate either inferiority or superiority of LB-100 plus doxorubicin as compared to doxorubicin alone.

A positive study would have the potential to change the standard therapy for this disease after four decades of failure to improve

the marginal benefit of doxorubicin alone.

Pharmacologic Study

the fourth quarter of 2019, the NCI enrolled the first two patients of a planned eight patient pharmacologic study of the ability

of LB-100 to enter the brain and penetrate recurrent brain tumors in patients where surgical removal of the cancers is indicated

(clinical trials registry NCT03027388).

This study is being conducted and funded by the NCI under a Cooperative Research and Development

Agreement with the Company;

additional information will be reported by the Company as it is provided by the NCI.

the fourth quarter of 2019, the National Cancer Institute (NCI) enrolled the first two patients of a planned eight patient pharmacologic

study of the ability of LB-100 to enter the brain and penetrate recurrent brain tumors in patients where surgical removal of the

cancers is indicated (clinical trials registry NCT03027388).

This study is being conducted and funded by the NCI under a Cooperative

Research and Development Agreement with us;

additional information will be reported by us as it is provided by the NCI.

malignant brain tumors (gliomas) are very challenging to treat.

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benefit gained by the addition of one or more anti-cancer drugs, but without major advances in overall survival for the majority

In animal models of GBM, the Company’s novel protein phosphatase inhibitor LB-100 enhances the effectiveness

of radiation, temozolomide chemotherapy treatments and immunotherapy, raising the possibility that LB-100 may improve outcomes

of standard GBM treatment in the clinic.

Although LB-100 has proven safe in patients at doses associated with apparent anti-tumor

activity against several human cancers arising outside the brain, the ability of LB-100 to penetrate tumor tissue arising in the

brain is not known.

Unfortunately, many drugs potentially useful for GBM treatment do not enter the brain in amounts necessary

for anti-cancer action.

In animal models of GBM, our novel protein phosphatase inhibitor LB-100 enhances the effectiveness of radiation,

temozolomide chemotherapy treatments and immunotherapy, raising the possibility that LB-100 may improve outcomes of standard GBM

treatment in the clinic.

Although LB-100 has proven safe in patients at doses associated with apparent anti-tumor activity against

several human cancers arising outside the brain, the ability of LB-100 to penetrate tumor tissue arising in the brain is not known.

Unfortunately, many drugs potentially useful for GBM treatment do not enter the brain in amounts necessary for anti-cancer action.

NCI study is designed to determine the extent to which LB-100 enters recurrent malignant gliomas.

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As a result of the innovative design

of the NCI study, data from so few patients should be sufficient to provide a sound rationale for a conducting a larger clinical

of the NCI study, data from so few patients should be sufficient to provide a sound rationale for conducting a larger clinical

trial to determine the effectiveness of adding LB-100 to the standard treatment regimen for GBMs.

Research Support Agreement with City of Hope National Medical Center

January 18, 2021, we executed a Clinical Research Support Agreement with City of Hope National Medical Center, an NCI-designated

comprehensive cancer center, and City of Hope Medical Foundation (collectively, “City of Hope”), to carry out a Phase

1b clinical trial of our first-in-class protein phosphatase inhibitor, LB-100, combined with a standard regimen for untreated,

extensive stage-disease small cell lung cancer (ED-SCLC).

LB-100 will be given in combination with carboplatin, etoposide and

atezolizumab, an FDA approved but marginally effective regimen, to previously untreated ED-SCLC patients.

The dose of LB-100 will

be escalated with the standard fixed doses of the 3-drug regimen to reach a recommended Phase 2 dose (RP2D).

Patient entry will

be expanded so that a total of 12 patients will be evaluable at the RP2D to confirm the safety of the LB-100 combination and to

look for potential therapeutic activity as assessed by objective response rate, duration of overall response, progression-free-survival

and overall survival.

cell lung cancer (SCLC) comprises about 15% of all lung cancers worldwide with about 30,000 new cases annually in the United States.

Although this aggressive neuroendocrine tumor is more sensitive to cytotoxic chemotherapy and radiation than the most common type

of lung cancer, SCLC patients soon relapse after treatment and have a dismal prognosis.

Recently, the addition of an immune blocker,

atezolizumab, to carboplatin plus etoposide showed for the first time in 20 years modest improvement in median progression- free

survival from 4.3 to 5.2 months and in median overall survival from 10.3 to 12.3 months.

In animal models, LB-100 significantly

enhances the antitumor activity of cytotoxic chemotherapy in general and in particular the combination of carboplatin and etoposide

against SCLC cells without enhancing toxicity.

the extensive preclinical data showing LB-100 increases the effectiveness of chemotherapy applies to patients, the Company believes

evidence of therapeutic benefit of LB-100 added to standard treatment of this very aggressive cancer could be revealed even in

this early clinical trial paving the way for a randomized Phase 3 study.

Perhaps even more important to the Company’s clinical

development of LB-100, evidence in this clinical trial of potentiation of cytotoxic therapy without an increase in toxicity simply

by the addition of LB-100 would justify clinical investigation of the added benefit of adding LB-100 to many widely used “standard”

cytotoxic regimens for a host of cancers.

Company estimates that from 24 to 30 patients will be needed to complete this clinical trial, at an estimated cost of $2,500,000

to $2,900,000, respectively.

If a significant number of patients fail during the dose-escalation process, an increase of up to

12 patients would likely be necessary, at an estimated additional cost of $800,000.

clinical trial is planned to commence during the quarter ending June 30, 2021, with patient accrual expected to take approximately

18 to 24 months to conduct.

If LB-100 does potentiate the benefit of the standard regimen, some evidence could be noted at 12

months into the clinical trial, but an assessment of potential increased activity is likely to require at least 24 months.

Trial Monitoring Agreements

September 12, 2018, we finalized a work order agreement with Theradex Systems, Inc.

(“Theradex”), an international

contract research organization, to monitor the Phase 1b/2 clinical trial being managed and conducted by Moffitt.

trial began in April 2019 and the first patient was entered into the clinical trial in July 2019.

At the current rate of accrual,

the trial would be completed over a period of four years from its initiation, with the final analysis and reporting expected by

Costs under this work order agreement are estimated to be approximately $954,000, with such payments expected to be

divided approximately 94% to Theradex for services and approximately 6% for payments for pass-through costs.

February 5, 2021, we signed a new work order agreement with Theradex to monitor the City of Hope investigator-initiated clinical

trial in small cell lung cancer in accordance with FDA requirements for oversight by the sponsoring party.

The Company estimates

that it will incur approximately $335,000 of costs under this work order agreement through September 30, 2023.

and License Agreements

March 22, 2018, we entered into a Patent Assignment and Exploitation Agreement with INSERM TRANSFERT SA, acting as delegatee of

the French National Institute of Health and Medical Research, for the assignment to us of INSERM’S interest in United States

9,833,450 entitled “Oxabicyloheptanes and Oxabicycloheptenes for the Treatment of Depressive and Stress Disorders,”

which was filed with the United States Patent and Trademark Office in the name of INSERM and us as co-owners on February 19, 2016

and granted on December 5, 2017, and related patent applications and filings.

INSERM is a French public institution dedicated

to research in the field of health and medicine that had previously entered into a Material Transfer Agreement with us to allow

INSERM to conduct research on our proprietary compound LB-100 and/or its analogs for the treatment of depressive or stress disorders

Pursuant to the Agreement, we have agreed to make certain milestone payments to INSERM aggregating up to $1,750,000

upon achievement of development milestones and up to $6,500,000 upon achievement of commercial milestones.

We also agreed to pay

INSERM certain commercial royalties on net sales of products attributed to the Agreement.

The exploitation of this patent for

the treatment of depressive and stress disorders in humans will require substantial additional capital and/or a joint venture

or other type of business arrangement with a pharmaceutical company with substantially greater capital and business resources

than those available to us.

As there can be no assurances that we will be able to obtain the capital or business resources necessary

to focus on the exploitation of this patent, it is uncertain when we may reach any of the development or commercialization milestones

under the Agreement, if at all.

April 2, 2018, we entered into a consulting agreement for a term of two years with Liberi Life Sciences Consultancy BV, located

in The Netherlands, for consulting and advisory services with respect to sales and licensing, as well as the procurement of investors

in China, Japan and South Korea.

The Consulting Agreement was extended for an additional period of one year.

The Consulting Agreement

provided for the payment of a fixed, one-time retainer of EURO 15,000 (US $18,348), which was paid on April 5, 2018, and 2.5%

of the net payments received by us from sales of products or licensing activities arising directly and exclusively from leads

generated by the advisor during the term of the Consulting Agreement, and any investors introduced to us by the advisor that results

in an investment in us during the term of the Consulting Agreement.

August 20, 2018, we entered into an Exclusive License Agreement with Moffitt.

Pursuant to the License Agreement, Moffitt granted

us an exclusive license under certain patents owned by Moffitt relating to the treatment of MDS and a non-exclusive license under

inventions, concepts, processes, information, data, know-how, research results, clinical data, and the like (other than the Licensed

Patents) necessary or useful for the practice of any claim under the Licensed Patents or the use, development, manufacture or

sale of any product for the treatment of MDS which would otherwise infringe a valid claim under the Licensed Patents.

obligated to pay Moffitt a non-refundable license issue fee of $25,000 after the first patient is entered into a Phase 1b/2 clinical

trial to be managed and conducted by Moffitt.

The clinical trial began at a single site in April 2019 and the first patient was

entered into the clinical trial in July 2019.

We are also obligated to pay Moffitt an annual license maintenance fee of $25,000

commencing on the first anniversary of the Effective Date and every anniversary thereafter until we commence payment of minimum

royalty payments.

We have also agreed to pay non-refundable milestone payments to Moffitt, which cannot be credited against earned

royalties payable by us, based on reaching various clinical and commercial milestones aggregating $1,897,000, subject to reduction

by 40% under certain circumstances relating to the status of Valid Claims, as such term is defined in the License Agreement.

of December 31, 2020, no milestones had yet been attained.

will be obligated to pay Moffitt earned royalties of 4% on worldwide cumulative net sales of royalty-bearing products, subject

to reduction to 2% under certain circumstances, on a quarterly basis, with a minimum royalty payment of $50,000 in the first four

years after sales commence, and $100,000 in year five and each year thereafter, subject to reduction by 40% under certain circumstances

relating to the status of Valid Claims, as such term is defined in the License Agreement.

Our obligation to pay earned royalties

under the License Agreement commences on the date of the first sale of a royalty-bearing product, and shall automatically expire

on a country-by-country basis on the date on which the last valid claim of the Licensed Patents expires, lapses or is declared

invalid, and the obligation to pay any earned royalties under the License Agreement shall terminate on the date on which the last

valid claim of the Licensed Patents expires, lapses, or is declared to be invalid in all countries.

Significant Agreements and Contracts

October 18, 2013, we entered into a Materials Cooperative Research and Development Agreement (M-CRADA) with the NINDS of the NIH

for a term of four years.

The Surgical Neurology Branch of NINDS is conducting research characterizing a variety of compounds

proprietary to us and is examining the potential of the compounds for anti-cancer activity, reducing neurological deficit due

to ischemia and brain injury, and stabilizing catalytic function of misfolded proteins for inborn brain diseases.

Under an M-CRADA,

a party provides research material, in this case proprietary compounds from our pipeline, for study by scientists at NIH.

exchange of material was for research only and did not imply any endorsement of the material on the part of either party.

the M-CRADA, the NIH grants a collaborator an exclusive option to elect an exclusive or non-exclusive commercialization license.

December 24, 2013, we entered into an agreement with NDA Consulting Corp.

for consultation and advice in the field of oncology

research and drug development.

As part of the agreement, NDA also agreed to cause its president, Dr.

Von Hoff, M.D.,

to become a member of our Scientific Advisory Committee.

The term of the agreement was for one year and provided for a quarterly

cash fee of $4,000.

The agreement has been automatically renewed for additional one-year terms on its anniversary date since 2014.

Consulting and advisory fees charged to operations pursuant to this agreement for the years ended December 31, 2020 and 2019 were

$16,000 and $16,000, respectively.

September 14, 2015, we entered into a Collaboration Agreement with BioPharmaWorks, pursuant to which we engaged BioPharmaWorks

to perform certain services for us.

Those services include, among other things:

(a) assisting us to (i) commercialize our products

and strengthen our patent portfolio, (ii) identify large pharmaceutical companies with potential interest in our product pipeline,

and (iii) prepare and deliver presentations concerning our products;

(b) at the request of the Board of Directors, serving as

backup management for up to three months should our Chief Executive Officer and scientific leader be temporarily unable to carry

out his duties;

and (d) identifying providers and overseeing

tasks relating to clinical use and commercialization of new compounds.

BioPharmaWorks

was founded in 2015 by former Pfizer scientists with extensive multi-disciplinary research and development and drug development

The Collaboration Agreement was for an initial term of two years and automatically renews for subsequent annual periods

unless terminated by a party not less than 60 days prior to the expiration of the applicable period.

In connection with the Collaboration

Agreement, we agreed to pay BioPharmaWorks a monthly fee of $10,000, subject to our right to pay a negotiated hourly rate in lieu

of the monthly payment and agreed to issue to BioPharmaWorks certain equity-based compensation.

In November 2016, it was mutually

agreed to suspend services and payments under the Collaboration Agreement, without extending its term, for the period from November

1, 2016 through March 31, 2017.

The Collaboration Agreement resumed as scheduled on April 1, 2017.

In April 2018, it was again

mutually agreed to suspend services and payments under the Collaboration Agreement, without extending its term, for the period

from February 1, 2018 through the September 13, 2019 anniversary date.

In February 2019, we subsequently agreed to resume the

Collaboration Agreement with BioPharmaWorks effective March 1, 2019, and the Collaboration Agreement is currently in effect.

August 12, 2020, we entered into a Master Service Agreement with the Foundation for Angelman Syndrome Therapy (FAST) to collaborate

in supporting preclinical studies of the potential benefit of LB-100 in a mouse model of Angelman Syndrome (AS) as reported in

The Proceedings of The National Academy of Science (Wang et al, June 3, 2019).

The preclinical studies will take place at The

University of California - Davis under the direction of Dr.

David Segal, an internationally recognized leader in AS research.

If the preclinical studies confirm that LB-100 reduces AS signs in rodent models, we have agreed to enter into discussions with

FAST with respect to possible collaborations to most efficiently assess the benefit of LB-100 in patients with AS, which is a

rare disease affecting an estimated one out of 12,000 to one out of 20,000 persons in the United States.

The genetic cause of

AS, reduced function of a specific maternal gene called Ube3, has been understood for some time, but the molecular abnormality

resulting from the genetic lesion has now been shown to be increased concentrations of protein phosphatase 2A (PP2A), a molecular

target of our investigational compound, LB-100.

We agreed to provide FAST with a supply of LB-100 to be utilized in the conduct

of this study, which is initially expected to be completed within three years.

Conditioned on FAST’s completion of this

study, we have agreed to pay FAST five percent (5%) of all proceeds, as defined in the Master Service Agreement, received by us,

up to a maximum of $250,000 from the exploitation of the study results.

Clinical Trials

below are clinical trials that the Company would currently consider conducting over the next few years.

The Company expects that

these potential clinical trials, and the details thereof, will change over time as the Company obtains more clinical information

The Company’s ability to conduct these clinical trials is subject to the availability of sufficient additional

financial resources.

below are clinical trials that we would currently consider conducting over the next few years.

We expect that these potential

clinical trials, and the details thereof, will change over time as we obtain more clinical information on LB-100.

to conduct these clinical trials is subject to the availability of sufficient additional financial resources.

A Phase 1b/2 randomized clinical trial in previously untreated patients with small cell lung cancer (SCLC) comparing the standard

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The malignant cells of this uniformly rapidly fatal lung

cancer are genetically sensitive to PP2A inhibition (by a process termed synthetic lethality).

cancer are genetically sensitive to PP2A inhibition (by a process termed “synthetic lethality”).

A Phase 1b/2 randomized clinical trial in patients adding LB-100 to PD-1 inhibitors against one of several cancers in which PD-1

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financing in excess of that currently budgeted to fund a Phase 1b/2 clinical trial in myelodysplastic syndrome that began in April

2019, and/or partnering relationships with other pharmaceutical companies, in order for the Company to undertake and complete

such clinical studies.

The Company is in discussions with various parties with respect to the financing of these clinical studies,

although there can be no assurances that the Company will be able to obtain such financing and/or partnering relationships on

acceptable terms or at all.

The Company’s longer-term objective is to secure one or more strategic partnerships with pharmaceutical

companies with major programs in cancer research and drug development.

following publications have included articles discussing the Company’s compounds:

May 2014 an article was published in Molecular Cancer Therapeutics reporting that LB-100 enhanced the therapeutic effectiveness

of chemotherapeutic drugs (doxorubicin and cisplatin) without significantly enhancing toxicity against HCC in animal models.

is the most common cancer in Asia and one of the leading causes of death from cancer worldwide.

October 2014, investigators reported in Cancer Letters that LB-100 enhanced the therapeutic effectiveness of chemotherapy in animal

models of pancreatic cancer can without significantly enhancing toxicity.

November 2014, investigators from the National Institutes of Health reported in Molecular Cancer Therapeutics that LB-100 overcomes

the resistance of cisplatin-resistant human ovarian cancer cells in the peritoneal cavity of animals.

This finding is of particular

interest as platinum-based chemotherapy drugs are the first-line treatment for women with unresectable ovarian cancer and patients

so treated eventually relapse because of development of platinum-resistant disease.

December 2014, scientists from the Terry Fox Cancer Center, Vancouver, British Columbia, reported at the Annual Society of Hematology

Meeting that LB-100 is active alone and potentiates the activity of Imatinib (Gleevec) against human cell lines of chronic myelogenous

leukemia (CML), both imatinib-naïve CML cells and Imatinib-resistant CML cells.

Although virtually all patients with CML

worldwide receive Imatinib as initial therapy and most patients have an excellent response, almost every patient relapses because

of development of Imatinib–resistance.

November 6, 2015, it was reported at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics,

Boston, Massachusetts, that in an ongoing Phase 1 clinical trial, LB-100 was associated with stabilization of a variety of advanced

cancers that had been progressing despite extensive prior treatment without dose-limiting toxicity.

The authors reporting this

development were Vincent Chung, City of Hope, Duarte, California;

Donald Richard, Texas Oncology, Tyler, Texas;

Fadi Braiteh,

Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada;

Kovach, Lixte Biotechnology Holdings, Inc.

East Setauket, New

and Aaron Scott Mansfield, May Clinic, Rochester, Minnesota

January 25, 2016, in the journal Nature Medicine, neuroscientists at the French Institute of Health and Medical Research (Inserm)

using a mouse model of depression identified protein phosphatase 2A (PP2A) as a potential pharmacological target for therapy.

Administration of LB-100, the Company’s proprietary inhibitor of PP2A, rapidly reduced depressive-like symptoms in these

conditioned animals.

January 4, 2017, the Company issued a news release to announce the publication online of Phase 1 results of the Company’s

novel anti-cancer compound in Clinical Cancer Research, entitled “Safety, tolerability, and preliminary activity of LB-100,

an inhibitor of protein phosphatase 2A, in patients with relapsed solid tumors”.

Ten (46.7%) of twenty-one patients receiving

at least 2 cycles of LB-100, a small molecule inhibitor of protein phosphatase (PP2A), achieved stable disease without limiting

toxicity for up to 15 cycles of therapy, including one patient with pancreatic cancer who had a partial regression.

PP2A has long

been recognized as a potentially important cancer treatment target, but its inhibition was thought to be too toxic for clinical

This Phase 1 clinical trial demonstrated the safety and tolerability of PP2A inhibition in patients with refractory solid

In numerous animal models of cancer, inhibition of PP2A by LB-100 enhanced the anti-tumor activity of standard chemotherapy

drugs and radiation without significantly enhancing their toxicity by altering cell cycle regulation and the DNA-damage repair

response pathways.

The mechanism by which LB-100 used alone apparently inhibited the growth of a variety of cancers in patients

in the recently completed Phase 1 clinical trial is not clear, but PP2A activity is reduced by mutation directly or indirectly

in many cancer types, rendering them vulnerable to pharmacologic inhibition of PP2A.

The Company believes that the results reported

in Clinical Cancer Research support further development of LB-100 alone and in combination with standard cytotoxic regimens for

a broad spectrum of tumors.

April 17, 2017, the Company issued a news release to announce the presentation of an abstract entitled “Protein phosphatase

2A inhibition with a novel small molecule inhibitor, LB-100, achieves durable immune-mediated antitumor activity when combined

with PD-1 blockage in a preclinical model”

as a poster (abstract number LB-193) at the American Association for Cancer Research

(AACR) Annual Meeting 2017 in Washington, D.C.

on April 4, 2017.

This research was done in collaboration with scientists at the

NINDS of the NIH.

The study showed that in an animal model, the Company lead clinical compound, LB-100, has a synergistic potential

in conjunction with immune checkpoint blockade supporting investigation of its ability to enhance immunotherapy in the clinic.

Based on a number of published pre-clinical studies, the Company had expected that LB-100 would be therapeutically useful primarily

as a potentiator of cytotoxic anti-cancer drugs and x-ray.

However, this study raises the possibility that LB-100 may also have

a role in enhancing the efficacy of so-called ‘immune checkpoint blockers’

–agents that allow the patients’

own immune system to attack their own cancers.

February 9, 2018, the Company issued a news release to announce that investigators at the Terry Fox Laboratory, British Columbia

Cancer Agency, Vancouver, British Columbia, Canada, reported on February 7,2018 (Lai et al., Sci.

10, eaan8735 (2018))

that in animal models the Company’s protein phosphatase 2A (PP2A) inhibitors overcome resistance of chronic myelogenous

leukemia (CML) cells to standard treatment.

The vast majority of CML cells are killed by drugs called tyrosine kinase inhibitors

(TKI), the prototype of which is imatinib (Gleevec), considered the first truly targeted form of chemotherapy.

Imatinib and subsequent

variants were a great advance in turning CML from a fatal to a controllable illness.

However, almost without exception, from the

onset of the disease some CML cells are resistant to TKI treatment so that continuous therapy is required and in some patients

the number of TKI resistant cells accelerates out of control.

The persistence and progression of CML despite TKI treatment is

believed to arise from a niche of intrinsically resistant leukemia stem cells.

The Terry Fox Laboratory investigators found inhibition

of PP2A with LB-100 or LB-102 preferentially sensitizes these resistant CML cells to killing by TKI compared to normal bone marrow

If these results can be replicated in the clinic, LB-100 and analogs may further improve the effectiveness of CML

March 29, 2018, it was reported in Nature Communications that LB-100 enhances the antitumor activity of an immune checkpoint inhibitor

(an anti-PD-1 drug) in two different mouse cancers.

This discovery raises the possibility that LB-100 may be a means for improving

the effectiveness of the rapidly expanding field of immune driven anti-cancer therapy.

Thus, the Company is developing clinical

protocols to test the hypothesis that the addition of LB-100 to an anti-PD-1 drug will improve the significant but low rates of

objective remission to anti-PD-1 treatment alone.

February 3, 2020, it was reported on-line in Cell Cycle that targeting PP2A with LB-100 inhibits the growth of human triple negative

breast cancer (TNBC) alone and in combination with standard chemotherapy in cell culture and animal models.

Of potential importance,

the improved antitumor activity of the chemotherapy drugs resulting from the addition of LB-100 did not enhance toxicity in the

TNBC comprises about 15% of all breast cancers and while initially responsive to cytototoxic chemotherapy almost always

Thus, TNBC may be another common cancer for which the incorporation of LB-100 into standard therapy may offer hope for

improved outcomes.

pre-clinical studies supporting the hypothesis that LB-100 may be an effective addition to standard regimens including immunotherapy

for the treatment of many human cancers was recently reviewed in the journal BBA-Molecular Cell Research (Mazhar et al 2019).

Company’s products will ultimately derive directly from its intellectual property and are expected to include the property

covered by its patents.

These patents now cover sole rights to the composition and synthesis of the LB-100 and LB-200 series of

Joint patent applications with the NIH have been filed for the treatment of glioblastoma multiforme, medulloblastoma, and

neuroblastoma.

The Company has also filed claims for the use of certain homologs of both series of drugs for the potential treatment

of neurodegenerative diseases such as Alzheimer’s Disease and Parkinson’s Disease, Amyotrophic Lateral Sclerosis (ALS,

or Lou Gehrig’s Disease), stroke, and traumatic brain injury, and of homologs of the LB-200 series for treatment of serious

systemic fungal infections and for the treatment of common fungal infections of the skin and nails.

for the LB-100 series (oxabicycloheptanes and heptenes) and the LB-200 series (histone deacetylase inhibitors;

HDACi) have been

filed in the United States and internationally under the Patent Cooperation Treaty.

Patents for composition of matter and for

several uses of both the LB-100 series and the LB-200 series have been issued in the United States, Mexico, Australia, Japan,

China, Hong Kong, Canada, Germany, France, the United Kingdom, the European Patent Office and the Eurasian Patent Office.

Company’s portfolio of 51 domestic and international patents issued is summarized below, of which 9 patents were issued

during the year ended December 31, 2019.

The Company has additional domestic and international patents pending.

2019, and/or partnering relationships with other pharmaceutical companies, in order for us to undertake and complete such clinical

We are in discussions with various parties with respect to the financing of these clinical studies, although there can

be no assurances that we will be able to obtain such financing and/or partnering relationships on acceptable terms or at all.

Our longer-term objective is to secure one or more strategic partnerships with pharmaceutical companies with major programs in

cancer research and drug development.

products will ultimately be based on our intellectual property and are expected to be covered by our patents.

These patents now

cover sole rights to the composition and synthesis of the LB-100 and LB-200 series of drugs, with coverage of the LB-200 series

now limited to those patents issued in the United States.

Joint patent applications with the NIH have been filed for the treatment

of glioblastoma multiforme, medulloblastoma, and neuroblastoma.

We have also filed patent applications for the use of certain

homologs of both series of drugs for the treatment of neurodegenerative diseases such as Alzheimer’s Disease and Parkinson’s

Disease, Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig’s Disease), stroke, and traumatic brain injury, and patent applications

for the use of homologs of the LB-200 series for the treatment of serious systemic fungal infections and for the treatment of

common fungal infections of the skin and nails.

applications for the LB-100 series (oxabicycloheptanes and heptenes) and the LB-200 series (histone deacetylase inhibitors;

have been filed in the United States and internationally under the Patent Cooperation Treaty.

Patents for composition of matter

and for several uses of both the LB-100 series and the LB-200 series have been issued in the United States, Mexico, Australia,

Japan, China, Hong Kong, Canada, Germany, France, the United Kingdom, and by the European Patent Office and the Eurasian Patent

For the LB-200 series, only patents issued in the United States are being maintained.

portfolio of domestic and international patents issued is summarized below.

We have additional domestic and international patents

Series of Compounds - Phosphatase Inhibitors –

2 unchanged sentences

and Oxabicycloheptenes, Their Preparation and Use

Priority Date or International Filing Date (non-U.S.

Priority Date or

International Filing Date

applications)

4 unchanged sentences

US 10,399,993

Series of Compounds –

LB-100 in Combination with Anti-Cancer Agents

for Regulating Cell Mitosis by Inhibiting Serine/Threonine Phosphatase

International

applications)

and LB-200 Series of Compounds –

2 unchanged sentences

Agents for the Prevention and Treatment of Neurodegenerative Diseases

International

Priority Date or

International Filing Date

applications)

Issue/Grant Date

Expiration Date

Oxabicycloheptanes

and Oxabicycloheptenes for the Treatment of Reperfusion Injury

International

Filing Date (non-U.S.

Priority Date or

International Filing Date (non-U.S.

applications)

ZL 201380035527.1

Issue/Grant Date

Expiration Date

Oxabicycloheptanes

and Oxabicycloheptenes for the Treatment of Depressive and Stress Disorders

International

Filing Date (non-U.S.

Priority Date or

International Filing Date (non-U.S.

applications)

International

Issue/Grant Date

Expiration Date

AU 2016219853

US 10,413,541

Priority Date or

International Filing Date

applications)

abicycloheptanes

Issue/Grant Date

Expiration Date

Oxabicycloheptanes

and Oxabicycloheptenes for the Treatment of Diabetes

International

Priority Date or

International Filing Date

applications)

Issue/Grant Date

Expiration Date

US 10,149,847

US 10,668,062

of Oxabicycloheptanes and Oxabicycloheptenes

International

Priority Date or

International Filing Date

applications)

ZL 201480027138.9

Issue/Grant Date

Expiration Date

AU 2014251087

US 10,532,050

of Synthesizing 3-(4-Methylpiperazine-1-Carbonyl)-7-Oxabicyclo [2.2.1] Heptane-2-Carboxylic Acid

International

Priority Date or

International Filing Date

applications)

Issue/Grant Date

Expiration Date

Phosphatase 2A Inhibitors for Treating Myelodysplastic Syndromes

International

Priority Date or

International Filing Date

applications)

Issue/Grant Date

Expiration Date

US 10,071,094

US 10,434,100

Oxabicycloheptane

International

Priority Date or

International Filing Date

applications)

Company has developed two series of pharmacologically active drugs, the LB-100 series and the LB-200 series.

The Company believes

that the mechanism by which compounds of the LB-100 series affect cancer cell growth is different from cancer agents currently

approved for clinical use.

Lead compounds from each series have activity against a broad spectrum of common and rarer human cancers

in cell culture systems.

In addition, compounds from both series have anti-cancer activity in animal models of glioblastoma multiforme,

neuroblastoma, and medulloblastoma, all cancers of neural tissue.

Lead compounds of the LB-100 series also have activity against

melanoma, breast cancer and sarcoma in animal models and enhance the effectiveness of commonly used anti-cancer drugs in these

model systems.

The enhancement of anti-cancer activity of these anti-cancer drugs occurs at doses of LB-100 that do not significantly

increase toxicity in animals.

It is therefore hoped that when combined with standard anti-cancer regimens against many tumor types,

the Company’s compounds will improve therapeutic benefit without enhancing toxicity in humans.

primary goal of the Company to date has been to take LB-100 through Phase 1 clinical trials.

Because of the novelty and spectrum

of activity of LB-100, the Company believes it is reasonably likely it will find a partner in the pharmaceutical industry with

interest in this compound at some stage of its clinical development.

However, the Company would prefer to delay the partnering/licensing

decision until the potential value of its products is augmented by demonstrating there is no impediment to clinical evaluation

and a therapeutic dose level is determined in clinical trials.

Demonstration of clinical usefulness would be expected to substantially

increase the value of the Company’s product.

Issue/Grant Date

Expiration Date

AU 2016263079

US 10,364,252

US 10,618,908

have developed two series of pharmacologically active drugs, the LB-100 series and the LB-200 series.

We believe that the mechanism

by which compounds of the LB-100 series affect cancer cell growth is different from cancer agents currently approved for clinical

Lead compounds from each series have activity against a broad spectrum of common and rarer human cancers in cell culture

In addition, compounds from both series have anti-cancer activity in animal models of glioblastoma multiforme, neuroblastoma,

and medulloblastoma, all cancers of neural tissue.

Lead compounds of the LB-100 series also have activity against melanoma, breast

cancer and sarcoma in animal models and enhance the effectiveness of commonly used anti-cancer drugs in these model systems.

enhancement of anti-cancer activity of these anti-cancer drugs occurs at doses of LB-100 that do not significantly increase toxicity

It is therefore hoped that when combined with standard anti-cancer regimens against many tumor types, our compounds

will improve therapeutic benefit without enhancing toxicity in humans.

primary goal to date has been to take our primary compound, LB-100, through Phase 2 clinical trials.

Because of the novelty and

spectrum of activity of LB-100, we believe it is reasonably likely we may find a partner in the pharmaceutical industry with interest

in this compound at some stage of its clinical development.

However, we would prefer to delay the partnering/licensing decision

until the potential value of our products are augmented by demonstrating there is no impediment to clinical evaluation and a therapeutic

dose level is determined in clinical trials.

Demonstration of clinical usefulness would be expected to substantially increase

the value of our product.

and Development

development of lead compounds in addition to LB-100 will require pharmacokinetic/pharmacodynamic characterization (i.e., how long

a drug persists in the blood and how long the drug is active at the intended target) and large animal toxicologic evaluation under

conditions meeting FDA requirements.

development of lead compounds in addition to LB-100 will require pharmacokinetic/ pharmacodynamic characterization (i.e., how

long a drug persists in the blood and how long the drug is active at the intended target) and large animal toxicologic evaluation

under conditions meeting FDA requirements.

Most anti-cancer drugs fail in development because of unacceptable toxicity.

analogy with mechanistically related compounds, there is good reason to believe that lead compounds in addition to LB-100 will

by analogy with mechanistically related compounds, there is good reason to believe that lead compounds in addition to LB-100 will

be able to be given to humans safely by routes and at doses resulting in concentration of drug producing anti-cancer activity

in animal model systems.

of the Company’s most valuable resources is its scientific team, a coalition of various experts brought together through

contracts and other collaborative arrangements.

The team has expertise in cancer biology, proteomics (cancer biomarkers), medicinal

and synthetic chemistry, pharmacology, clinical oncology and drug evaluation.

In a relatively short period of time and at low

cost, this group has developed lead compounds of two different classes of drugs that are positioned for development as new treatments

for several types of cancer.

Company is subject to FDA regulations as it conducts clinical trials.

Additionally, any product for which the Company obtains

marketing approval, along with the manufacturing processes, post-approval clinical data and promotional activities for such product,

will be subject to continual review and periodic inspections by the FDA and other regulatory bodies.

Even if regulatory approval

of a product is granted, the approval may be subject to limitations on the indicated uses for which the product may be marketed

or contain requirements for costly post-marketing testing and surveillance to monitor the safety or efficacy of the product.

discovery of previously unknown problems with the Company’s products, including unanticipated adverse events or adverse

events of unanticipated severity or frequency, manufacturer or manufacturing processes, or failure to comply with regulatory requirements,

may result in restrictions on such products or manufacturing processes, withdrawal of the products from the market, voluntary

or mandatory recall, fines, suspension of regulatory approvals, product seizures, injunctions or the imposition of civil or criminal

of our most valuable resources is our scientific team, a coalition of various experts brought together through contracts and other

collaborative arrangements.

The team has expertise in cancer biology, proteomics (cancer biomarkers), medicinal and synthetic

chemistry, pharmacology, clinical oncology and drug evaluation.

In a relatively short period of time and at low cost, this group

has developed lead compounds of two different classes of drugs that are positioned for development as new treatments for several

types of cancer.

are subject to FDA regulations as it conducts clinical trials.

Additionally, any product for which we obtain marketing approval,

along with the manufacturing processes, post-approval clinical data and promotional activities for such product, will be subject

to continual review and periodic inspections by the FDA and other regulatory bodies.

Even if regulatory approval of a product

is granted, the approval may be subject to limitations on the indicated uses for which the product may be marketed or contain

requirements for costly post-marketing testing and surveillance to monitor the safety or efficacy of the product.

Later discovery

of previously unknown problems with our products, including unanticipated adverse events or adverse events of unanticipated severity

or frequency, manufacturer or manufacturing processes, or failure to comply with regulatory requirements, may result in restrictions

on such products or manufacturing processes, withdrawal of the products from the market, voluntary or mandatory recall, fines,

suspension of regulatory approvals, product seizures, injunctions or the imposition of civil or criminal penalties.

life sciences industry is highly competitive and subject to rapid and profound technological change.

The Company’s present

and potential competitors include major pharmaceutical companies, as well as specialized biotechnology and life sciences firms

in the United States and in other countries.

Most of these companies have considerably greater financial, technical and marketing

resources than the Company does.

Additionally, mergers and acquisitions in the pharmaceutical and biotechnology industries may

result in even more resources being concentrated in the Company’s competitors.

The Company’s existing or prospective

competitors may develop processes or products that are more effective than the Company’s or be more effective at implementing

their technologies to develop commercial products faster.

The Company’s competitors may succeed in obtaining patent protection

and/or receiving regulatory approval for commercializing products before the Company does.

Developments by the Company’s

competitors may render the Company’s product candidates obsolete or non-competitive.

Company also experiences competition from universities and other research institutions, and the Company is likely to compete with

others in acquiring technology from those sources.

There can be no assurance that other organizations will not develop technologies

with significant advantages over those that the Company is seeking to develop.

Any such development could harm the Company’s

Company competes with universities and other research institutions engaged in research in these areas.

Many of the Company’s

competitors have greater technical and financial resources than the Company does.

Company’s ability to compete successfully is based on numerous factors, including:

cost-effectiveness of any product that the Company ultimately commercializes relative to competing products;

ease of use and ready availability of any product that the Company brings to market;

relative speed with which the Company is able to bring any product resulting from its research to market in its target markets.

the Company is unable to distinguish its products from competing products, or if competing products reach the market first, the

Company may be unable to compete successfully with current or future competitors.

of December 31, 2019, the Company had no full-time employees, other than Dr.

Kovach directs, coordinates and manages

the scientific and business development of the Company with the advice of the Company’s Board of Directors, input from the

Scientific Advisory Committee, and, from time to time, various consultants with specific expertise.

Our present and potential

competitors include major pharmaceutical companies, as well as specialized biotechnology and life sciences firms in the United

States and in other countries.

Most of these companies have considerably greater financial, technical and marketing resources

Additionally, mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more

resources being concentrated in our competitors.

Our existing or prospective competitors may develop processes or products that

are more effective than ours or be more effective at implementing their technologies to develop commercial products faster.

competitors may succeed in obtaining patent protection and/or receiving regulatory approval for commercializing products before

Developments by our competitors may render our product candidates obsolete or non-competitive.

also experience competition from universities and other research institutions, and we are likely to compete with others in acquiring

technology from those sources.

There can be no assurance that other organizations will not develop technologies with significant

advantages over those that we are seeking to develop.

Any such development could harm our business.

compete with universities and other research institutions engaged in research in these areas.

Many of our competitors have greater

technical and financial resources than we do.

ability to compete successfully is based on numerous factors, including:

cost-effectiveness of any product that we ultimately commercialize relative to competing products;

ease of use and ready availability of any product that we bring to market;

relative speed with which we are able to bring any product resulting from its research to market in our target markets.

we are unable to distinguish our products from competing products, or if competing products reach the market first, we may be

unable to compete successfully with current or future competitors.

and Human Capital Resources

of March 12, 2021, we had three full-time employees and one part-time employee.

We consider our relationship with our employees

Our future performance depends significantly upon the continued service of our key personnel and our ability to attract

highly skilled employees.

We provide our employees with opportunities for equity ownership.

of March 12, 2021, we do not operate any facilities, but contract out research and development activities, drug production, and

drug storage to various commercial laboratories, drug manufacturers and storage facilities.

done under the CRADA were carried out in compliance with applicable Statutes, Executive Capital Orders, HHS regulations and all

FDA, CDC, and NIH policies as specified in Article 13, 13.1 and 13.2, of the PHS CRADA.

Company’s business is subject to the regulations of the FDA as it conducts clinical trials.

Clinical trials are research

studies to answer specific questions about new therapies or new ways of using known treatments.

Clinical trials determine whether

new drugs or treatments are both safe and effective and the FDA has determined that carefully conducted clinical trials are the

fastest and safest way to find treatments that work in people.

business is subject to the regulations of the FDA as it conducts clinical trials.

Clinical trials are research studies to answer

specific questions about new therapies or new ways of using known treatments.

Clinical trials determine whether new drugs or treatments

are both safe and effective and the FDA has determined that carefully conducted clinical trials are the fastest and safest way

to find treatments that work in people.

FDA also requires that an independent review body consider the benefits and risks of a clinical trial and grant approval for the

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is established.

addition to regulations imposed by the FDA, depending on the Company’s future activities, the Company may become subject

to regulation under various federal and state statutes and regulations, such as the Occupational Safety and Health Act, the Environmental

Protection Act, the Toxic Substances Control Act, the Research Conservation and Recovery Act, national restrictions on technology

transfer, and import, export and customs regulations.

From time to time, other federal agencies and congressional committees have

indicated an interest in implementing further regulation of biotechnology applications.

The Company is not able to predict whether

any such regulations will be adopted or whether, if adopted, such regulations will apply to the Company’s business, or whether

the Company or its collaborators would be able to comply with any applicable regulations.

addition, as the Company intends to market its products in international markets, the Company may be required to obtain separate

regulatory approvals from the European Union and many other foreign jurisdictions.

Approval by the FDA does not ensure approval

by regulatory authorities in other countries, and approval by one foreign regulatory authority does not ensure approval by regulatory

authorities in other foreign countries or by the FDA.

The Company may not be able to file for regulatory approvals and may not

receive necessary approvals to commercialize its products in any market.

addition to regulations imposed by the FDA, depending on our future activities, we may become subject to regulation under various

federal and state statutes and regulations, such as the Occupational Safety and Health Act, the Environmental Protection Act,

the Toxic Substances Control Act, the Research Conservation and Recovery Act, national restrictions on technology transfer, and

import, export and customs regulations.

From time to time, other federal agencies and congressional committees have indicated

an interest in implementing further regulation of biotechnology applications.

We are not able to predict whether any such regulations

will be adopted or whether, if adopted, such regulations will apply to our business, or whether we or our collaborators would

be able to comply with any applicable regulations.

addition, as we intend to market our products in international markets, we may be required to obtain separate regulatory approvals

from the European Union and many other foreign jurisdictions.

Approval by the FDA does not ensure approval by regulatory authorities

in other countries, and approval by one foreign regulatory authority does not ensure approval by regulatory authorities in other

foreign countries or by the FDA.

We may not be able to file for regulatory approvals and may not receive necessary approvals to

commercialize our products in any market.

may be involved from time to time in ordinary litigation, negotiation, and settlement matters that will not have a material effect

on our operations or finances.

We are not currently party to any material legal proceedings, and we are not aware of any pending

or threatened litigation against us.

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