What changed in this filing

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Item 1. Business

2023-03-29 compared with 2022-03-21 · 248 added, 280 removed, 357 unchanged (60% of the section changed)

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 use.

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

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 animal models.

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, 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.

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.

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 corporate office is located in Pasadena, California.

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.

The Company believes that inhibitors of protein phosphatases have broad therapeutic

potential not only for cancer but also for other debilitating and life-threatening diseases.

The Company is directing its efforts on

clinical development of a specific protein phosphatase inhibitor, referred to as LB-100, which has been shown to have clinical anti-cancer

activity at doses that produce little or no toxicity.

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

has not yet commenced any revenue-generating operations, does not have positive cash flows from operations, relies on stock-based compensation

for a substantial portion of employee and consultant compensation, and is dependent on periodic infusions of equity capital to fund its

operating requirements.

Clinical Trial Activities

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series of compounds.

Our current focus is on the clinical development of the LB-100 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 of

not only several types of cancer but also vascular and metabolic diseases.

The LB-200 series contains compounds which have the potential

to be the most effective in its class and may be useful for the treatment of chronic hereditary diseases, such as Gaucher’s disease,

in addition to cancer and neurodegenerative diseases.

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

barrier” which protects the brain from exposure to potentially toxic substances in the blood.

Because there is no certainty 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.

have demonstrated that the lead compound of the LB-100 series is 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.

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.

More recently,

the LB-100 compounds have been shown to potentiate the relatively new category of drugs called immune blockers.

Because the LB-100 compounds

appear to exert their ability to improve the effectiveness of different forms of chemotherapy, radiation therapy and immunotherapy, 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).

Many pharmaceutical companies are also developing drugs of this type,

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

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 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.

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 issued in the United

Collaborations

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Cancer Center Clinical Trial Research Agreement

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).

August 20, 2018, the Company 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 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.

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well as to provide funding for the clinical trial.

The goal was to enter approximately 150 patients in this clinical trial over a period

The goal is to enter approximately 150 patients in this clinical trial over a period

of two years.

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

regulations were adopted subsequent to the production of the Company’s existing LB-100 inventory.

new batch of LB 100 has been prepared and is now undergoing the multitude of analytical studies of the formulated product necessary to

gain approval for use in the European Union.

Regulatory reviews by the European Union have been delayed, as a result of which the final

review of the clinical product by Spanish regulatory authorities will also be delayed.

Accordingly, the clinical trial is now estimated

to begin during the quarter ending June 30, 2022 and be completed by June 30, 2025.

interim analysis of this clinical trial could indicate either inferiority or superiority of LB-100 plus doxorubicin as compared to doxorubicin

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.

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

standards were adopted subsequent to the production of the Company’s existing LB-100 inventory.

order to manufacture a new inventory supply of LB-100 for the GEIS clinical trial, the Company 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 included

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, also under

The API was then transferred to a vendor that prepares the clinical drug product, also under

GMP conditions documented by an independent auditor.

The clinical drug product is then sent to a vendor to test for purity and sterility,

The clinical drug product was 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.

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authorities for review and approval before being used in a clinical trial.

November 2, 2021, the Company entered into a Development Agreement with Famar Health Care Services Madrid SA to prepare a new batch of

clinical LB-100 for use in clinical trials to be conducted in the European Union.

Pharmacologic Study

October 13, 2022, the Company announced that the Spanish Agency for Medicines and Health Products (Agencia Española de Medicamentos

y Productos Sanitarios or “AEMPS”) had authorized a Phase 1b/randomized Phase 2 study of LB-100, the Company’s lead

clinical compound, plus doxorubicin, versus doxorubicin alone, the global standard for initial treatment of advanced soft tissue sarcomas

Consequently, the GEIS clinical trial is currently scheduled to commence during the quarter ending June 30, 2023 and to be completed

by December 31, 2025.

Up to 170 patents will be entered into the clinical trial.

The Phase 1b section of the protocol is expected to

be completed by June 30, 2024, at which time the Company expects to have data on both response and toxicity from this portion of the

clinical trial.

interim analysis of this clinical trial will be done before full accrual of patients is completed to determine whether the study has

the possibility of showing superiority of the combination of LB-100 plus doxorubicin 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.

Cancer Institute Pharmacologic Clinical Trial

May 2019, the National Cancer Institute (NCI) initiated a glioblastoma (GBM) pharmacologic clinical trial.

During 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 being required

to provide the LB-100 clinical compound.

This study is being conducted

and funded by the NCI under a Cooperative Research and Development Agreement, with the Company being required to provide the LB-100 clinical

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

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present and to determine whether the cells in the tumors show the biochemical changes expected to be present if LB-100 reaches its molecular

The goal is to obtain data in up to eight patients.

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 conducting a larger clinical trial to determine the effectiveness of adding LB-100

to the standard treatment regimen for GBMs.

neurosurgical unit at the NCI, which had been closed due to the Covid-19 epidemic, has reopened, and patient accrual has resumed.

entry remains at two, with the goal to enter eight patients before analyzing results.

There is an urgent need to improve therapy for

this type of aggressive brain tumor.

If the NCI study shows that LB-100 does penetrate the brain, a clinical study of LB-100 in combination

with standard therapy for GBM, the drug temozolomide and radiation, both of which have been well documented in pre-clinical studies to

be significantly enhanced by LB-100, would be of significant interest to neuro-oncologists frustrated by decades of limited advances

in therapy for this common brain tumor in adults.

As a result of the innovative design of the NCI study, data from a 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.

patients have been entered and analysis of the blood and tissue will now proceed.

If there is evidence in at least two of the patients

of penetration of LB 100 into tumor tissue, the study will be deemed as successful.

The results of this study are expected during 2023.

Research Support Agreement with City of Hope National Medical Center

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clinical trial was initiated on March 9, 2021, with patient accrual expected to take approximately two years to complete.

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.

The Company is currently seeking to add two additional centers

to increase the rate of accrual.

The Company expects this clinical trial to be completed by June 30, 2024.

clinical trial is based upon a target of 42 enrollees.

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

increase of up to 12 patients would likely be necessary.

The Company currently expects that enrollment in this clinical trial will range

from approximately 18 to 30 enrollees, with 24 enrollees as the most likely number.

Should fewer than 42 enrollees be required, the Company

has agreed to compensate City of Hope on a per enrollee basis

patient accrual has been slower than expected, the Company is currently seeking to add two additional sites to increase the rate of patient

accrual, with at least one major site expected to be added by June 30, 2023.

With the additional sites, the Company expects that this

clinical trial will be completed by December 31, 2024.

Without the additional sites, the Company expects that this clinical trial will

be completed no sooner than December 31, 2025.

March 6, 2023, Sarah Cannon Research Institute (SCRI), Nashville, Tennessee, joined the City of Hope’s ongoing Phase 1b clinical

trial to assess the combination of the Company’s first-in-class protein phosphatase 2A (PP2A) inhibitor, LB-100, with a standard

regimen for previously untreated, extensive stage small cell lung cancer disease.

SCRI, one of the largest community-based cancer trial

centers in the United States, is expected to expedite and expand the accrual of patients to this clinical trial, thus reducing the time

required to demonstrate the feasibility, tolerability and efficacy of adding LB-100 to the current standard treatment regimen.

Company currently expects that enrollment in this clinical trial will range from approximately 18 to 30 enrollees, with 24 enrollees

as the most likely number.

Should fewer than 42 enrollees be required, the Company has agreed to compensate City of Hope on a per enrollee

If a significant improvement in outcome is seen with the addition of LB-100, this would be an important advance in the treatment

of a very aggressive disease.

Trial Monitoring Agreements

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and License Agreements

March 22, 2018, the Company 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 the Company of INSERM’S interest in United

States Patent No.

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 the Company as co-owners on February 19,

2015 and granted on May 12, 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 the Company to allow INSERM to

conduct research on the Company’s proprietary compound LB-100 and/or its analogs for the treatment of depressive or stress disorders

Pursuant to the Agreement, the Company has 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.

The Company also agreed to

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

The Company’s initial plan was to

complete the validation process to evaluate LB-100 for the treatment of depressive or stress disorders in humans within three years;

however, 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 the Company.

As there can be no assurances that the Company will be able to obtain the

capital or business resources necessary to focus on the exploitation of this patent, it is uncertain as to when, if at all, the Company

may reach any of the development or commercialization milestones under the Agreement.

As of December 31, 2021 and 2020, no amounts were

due under this agreement.

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

Pursuant to the License Agreement, Moffitt granted

the Company an exclusive license under certain patents owned by Moffitt (the “Licensed Patents”) 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

The Company was 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.

The Company is 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 the Company commences

payment of minimum royalty payments.

The Company has also agreed to pay non-refundable milestone payments to Moffitt, which cannot be

credited against earned royalties payable by the Company, 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

During the years ended December 31, 2021 and 2020, the Company recorded charges to operations of $24,999 and $25,001, respectively,

in connection with its obligations under the License Agreement.

Effective August 20, 2018, the Company entered into an Exclusive License Agreement with Moffitt.

Pursuant to the License Agreement,

Moffitt granted the Company an exclusive license under certain patents owned by Moffitt (the “Licensed Patents”) 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.

The Company was obligated to pay Moffitt a non-refundable license issue fee of $25,000 after the first patient

was 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.

The Company is 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 the Company

commences payment of minimum royalty payments.

The Company has also agreed to pay non-refundable milestone payments to Moffitt, which

cannot be credited against earned royalties payable by the Company, 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.

During the years ended December 31, 2022 and 2021, the Company recorded charges to operations of $25,000 and $25,000,

respectively, in connection with its obligations under the License Agreement.

As of December 31, 2022, no milestones had yet been attained.

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Significant Agreements and Contracts

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

for consultation and advice in the field of oncology

research and drug development.

Consulting Corp.

On December 24, 2013, the Company 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 the Company’s Scientific Advisory Committee.

Von Hoff, M.D., to become a member of the Company’s Scientific Advisory Committee.

The term of the agreement was for one year

The agreement has been automatically

renewed for additional one-year terms on its anniversary date since 2014.

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

to perform certain services for the Company.

Those services included, among other things:

(a) assisting the Company to (i) commercialize

its products and strengthen its patent portfolio, (ii) identify large pharmaceutical companies with potential interest in the Company’s

product pipeline, and (iii) prepare and deliver presentations concerning the Company’s products;

(b) at the request of the Board

of Directors, serving as backup management for up to three months should the Company’s 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.

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.

BioPharmaWorks .

Effective September 14, 2015, the Company entered into a Collaboration Agreement with BioPharmaWorks, pursuant to which the Company engaged

BioPharmaWorks to perform certain services for the Company.

Those services included, among other things, assisting the Company to commercialize

its products and strengthen its patent portfolio;

identifying large pharmaceutical companies with a potential interest in the Company’s

product pipeline;

assisting in preparing technical presentations concerning the Company’s products;

consultation in drug discovery

and development;

and identifying providers and overseeing tasks relating to clinical development of new compounds.

BioPharmaWorks

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

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

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

in supporting pre-clinical 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 pre-clinical studies will be conducted at The University of California

- Davis under the direction of Dr.

David Segal, an internationally recognized leader in AS research.

If the pre-clinical studies confirm

that LB-100 reduces AS signs in rodent models, the Company has 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 the Company’s investigational compound, LB-100.

has 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, the Company has agreed to pay FAST five percent (5%) of all

proceeds, as defined in the Master Service Agreement, received by the Company, up to a maximum of $250,000 from the exploitation of the

study results.

research team at the University of California, Davis recently completed their pre-clinical study of the potential benefit of LB-100 in

a mouse model of AS, and the results are currently under review by FAST.

The preliminary analysis indicates that the positive results

previously reported by Chinese investigators were not confirmed in the US model.

The Company is awaiting input from FAST as to whether

it intends to continue to pursue pre-clinical studies of LB 100.

October 8, 2021, the Company entered into a Development Collaboration Agreement with the Netherlands Cancer Institute, Amsterdam (NKI),

one of the world’s leading comprehensive cancer centers, and Oncode Institute, Utrecht, a major independent cancer research center,

to identify the most promising drugs to be combined with LB-100, and potentially LB-100 analogues, to be used to treat a range of cancers,

as well as to identify the specific molecular mechanisms underlying the identified combinations.

The Company has agreed to fund the study

and provide a sufficient supply of LB-100 to conduct the study.

The study is expected to take approximately two years to conduct.

In connection with the Collaboration Agreement, the

Company agreed to pay BioPharmaWorks a monthly fee of $10,000, subject to the right of the Company to pay a negotiated hourly rate in

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

for Angelman Syndrome Therapy .

Effective August 12, 2020, the Company entered into a Master Service Agreement with the Foundation

for Angelman Syndrome Therapy (FAST) to collaborate in supporting pre-clinical 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 pre-clinical

studies were to be conducted at The University of California - Davis under the direction of Dr.

David Segal, an internationally recognized

leader in AS research.

If the pre-clinical studies confirm that LB-100 reduces AS signs in rodent models, the Company has 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 the

Company’s investigational compound, LB-100.

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

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

Conditioned on FAST’s completion of this

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

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

research team at the University of California - Davis recently completed their pre-clinical study of the potential benefit of LB-100

in a mouse model of AS.

The preliminary analysis indicates that the positive results previously reported by Chinese investigators were

not confirmed in the US model.

The Company is currently awaiting input from FAST as to whether it intends to continue to pursue pre-clinical

studies of LB 100.

To date, FAST has not indicated whether it desires to pursue further studies of LB-100, but in light of the failure

to confirm the Chinese study results, the Company does not plan to pursue further studies of AS.

Cancer Institute.

On October 8, 2021, the Company entered into a Development Collaboration Agreement with the Netherlands Cancer

Institute, Amsterdam, one of the world’s leading comprehensive cancer centers, and Oncode Institute, Utrecht, a major independent

cancer research center, to identify the most promising drugs to be combined with LB-100, and potentially LB-100 analogues, to be used

to treat a range of cancers, as well as to identify the specific molecular mechanisms underlying the identified combinations.

has agreed to fund the study and provide a sufficient supply of LB-100 to conduct the study.

The study is expected to take approximately

two years to conduct.

The Company has contracted with MRI Global for stability analysis, storage and distribution of LB-100 for clinical trials

in the United States.

On June 10, 2022, the contract was amended to reflect an estimated completion date of April 30, 2023.

Future Clinical Trials

below is a clinical trial that we would currently consider conducting over the next few years.

We expect that this potential clinical

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

Our ability to conduct this clinical

trial, and possibly other clinical trials, is subject to the availability of sufficient additional financial resources.

Phase 1b/2 randomized clinical trial in patients adding LB-100 to PD-1 inhibitors against

one of several cancers in which PD-1 inhibitors alone have definite but modest activity.

objective is to initiate a Phase 1b/2 immunotherapy clinical trial in 2023.

Our ability to conduct such a clinical trial, and possibly

other clinical trials, is subject to the availability of additional financial resources.

The clinical trial would study the ability of

LB-100 to enhance the effectiveness of adding LB-100 to an immunoblocker in treatment of one of several cancers in which immunotherapy

alone has modest activity.

Phase 1b/2 clinical trial in LB-100 plus a PD-1 inhibitor in yet to be specified solid tumors would require additional 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 us to undertake and complete such clinical studies.

From time to time,

we engage 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.

of that currently budgeted and/or partnering relationships with other pharmaceutical companies.

From time to time, we engage discussions

with various parties with respect to the financing immunotherapy clinical trials.

There is no assurance 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;

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 Office.

For the LB-200 series,

only patents issued in the United States are being maintained.

sole rights to the composition and synthesis of our LB-100 series of drugs, which is the Company’s lead clinical compound in development.

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

applications for the LB-100 series (oxabicycloheptanes and heptenes) have been filed in the United States and internationally under the

Patent Cooperation Treaty.

Patents for composition of matter and for several uses of the LB-100 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 Office.

we do not plan to allocate resources to further develop our LB-200 series of drugs, we have patents that cover sole rights to the composition

and synthesis of the LB-200 series of drugs, with coverage of the LB-200 series now limited to those patents issued in the United States.

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

Company strives to protect and enhance the proprietary technology, inventions, and improvements that are commercially important to the

development of its business, including seeking, maintaining, and defending its patent rights.

The Company also relies on trade secrets

relating to its proprietary pipeline of product candidates and on know-how and continuing technological innovation to develop and strengthen

its pipeline.

The Company intends to rely on regulatory protection afforded by regulatory agencies through data exclusivity, market exclusivity,

and patent term extensions, where available.

development of its business, including seeking, maintaining, and defending its patent rights, which are owned solely by our wholly-owned

Delaware subsidiary, Lixte Biotechnology, Inc., except in two instances jointly with one of our collaborators.

The Company also relies

on trade secrets relating to its proprietary pipeline of product candidates and on know-how and continuing technological innovation to

develop and strengthen its pipeline.

The Company intends to rely on regulatory protection afforded by regulatory agencies through data

exclusivity, market exclusivity, and patent term extensions, where available.

Company’s success will depend in large part on its ability to obtain and maintain patent and other proprietary protection for commercially

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be sure that any of the Company’s existing patents or any patents that may be granted to us in the future will be commercially

useful in protecting the Company’s commercial products or therapeutic method;

and the Company cannot be sure that an agency or

court would determine that the Company’s solely or jointly owned patents are valid and enforceable.

descriptive summary of the patent portfolio for the Company’s most important clinical programs involving the development of LB-100

is presented below, followed by a detailed listing of each domestic and international patent that has been issued.

Lixte Biotechnology,

is the Company’s wholly-owned Delaware subsidiary.

The projected patent expiration dates noted below assume that that all

required maintenance or annuity fees for the patents are timely paid and that a court or agency does not determine that the patents are

invalid or unenforceable.

useful in protecting the Company’s intended commercial products or therapeutic methods;

and the Company cannot be sure that an

agency or court would determine that the Company’s solely or jointly owned patents are valid and enforceable.

patent portfolios for the Company’s most important programs involving the development of the LB-100 series are summarized and presented

below, along with related information, as of December 31, 2022, followed by a detailed listing of each domestic and international patent

that has been issued.

The projected patent expiration dates noted below assume that that all required maintenance or annuity fees for

the patents are timely paid and that a court or agency does not determine that the patents are invalid or unenforceable.

The Company’s lead compound LB-100 is covered by U.S.

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Combination Therapy with a Checkpoint Inhibitor .

LB-100 combination therapy with a checkpoint inhibitor for treating gliomas

is covered by pending U.S.

patent applications.

These patent applications are jointly owned by Lixte Biotechnology, Inc.

and The United States of America, as represented by the Secretary, Department of Health and Human Services.

Patents issuing from these

patent applications are projected to expire in 2037, exclusive of any patent term extension.

Combination Therapy with Carboplatin, Etoposide or Atezolizumab .

LB-100 combination therapy with carboplatin, etoposide or atezolizumab

for treating small-cell lung cancer is covered by an international patent application that is solely owned by Lixte Biotechnology, Inc.

Patents issuing from this patent application are projected to expire in 2041, exclusive of any patent term extension.

Combination Therapy with Other Investigational Compounds .

LB-100 combination therapy with a checkpoint inhibitor for treating cancer is

covered by a pending U.S.

patent application and by non-U.S.

patents and patent applications.

These patents and patent applications are

jointly owned by Lixte Biotechnology, Inc.

and The United States of America, as represented by the Secretary, Department of Health and

Human Services.

These patents and patents issuing from these patent applications are projected to expire in 2037, exclusive of any patent

term extension.

Combination Therapy with Carboplatin, Etoposide and Atezolizumab .

LB-100 combination therapy with carboplatin, etoposide and

atezolizumab for treating small-cell lung cancer is covered by pending U.S., Taiwanese and international patent applications that are

solely owned by Lixte Biotechnology, Inc.

Patents issuing from these patent applications are projected to expire in 2041, exclusive of

any patent term extension.

Combination Therapy with Another Investigational Compound .

LB-100 combination therapy with one of several other investigational

compounds for treating a wide-array of cancers is covered by a U.S.

provisional patent application that is jointly owned by Lixte Biotechnology,

and Stichting Het Nederlands Kanker Instituut – Antoni Van Leeuwenhoek Ziekenhuis.

Patents issuing from counterpart nonprovisional

applications are projected to expire in 2043, exclusive of any patent term extension.

Therapeutic Methods .

Administration of LB-100 for treating myelodysplastic syndrome is covered by U.S.

compounds for treating cancer, or preventing, inhibiting or reducing risk of metastasis of the cancer, is covered by pending U.S., Tawainese

and international patent applications that are jointly owned by Lixte Biotechnology, Inc.

and Stichting Het Nederlands Kanker Instituut

– Antoni Van Leeuwenhoek Ziekenhuis.

Patents issuing from these patent applications are projected to expire in 2043, exclusive

of any patent term extension.

for Treating Myelodysplastic Syndrome .

LB-100 for treating myelodysplastic syndrome is covered by U.S.

and 10,071,094, which are jointly owned by Lixte Biotechnology, Inc.

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counterparts are projected to expire in 2035, exclusive of any patent term extension.

Administration of LB-100

for treating breast cancer, colon cancer, large cell lung cancer, adenocarcinoma of the lung, small cell lung cancer, stomach cancer,

liver cancer, ovary adenocarcinoma, pancreas carcinoma, prostate carcinoma, promyelocytic leukemia, chronic myelocytic leukemia or acute

lymphocytic leukemia, is covered by U.S.

9,079,917, which is solely owned by Lixte Biotechnology, Inc.

This patent and its

for Treating Cancer .

LB-100 for treating breast cancer, colon cancer, large cell lung cancer, adenocarcinoma of the lung, small

cell lung cancer, stomach cancer, liver cancer, ovary adenocarcinoma, pancreas carcinoma, prostate carcinoma, promyelocytic leukemia,

chronic myelocytic leukemia or acute lymphocytic leukemia, is covered by U.S.

9,079,917, which is solely owned by Lixte Biotechnology,

This patent and its non-U.S.

counterparts are projected to expire in 2028, exclusive of any patent term extension.

The Company’s LB-100 prodrugs are covered by U.S.

10,618,908, 9,988,394, 8,822,461, 8,227,473 and

7,998,957, which are solely owned by Lixte Biotechnology, Inc.

Prodrugs and Analogs .

LB-100 prodrugs and analogs are covered by U.S.

10,618,908, 9,988,394, 8,822,461, 8,227,473

and 7,998,957, which are solely owned by Lixte Biotechnology, Inc.

These patents and their non-U.S.

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in 2036, 2030 or 2028, exclusive of any patent term extension.

Pharmaceutical compositions of LB-100 prodrugs are covered by U.S.

11,236,102, 10,532,050, 10,023,587, 8,822,461, 8,227,473 and 7,998,957, which are solely owned by Lixte Biotechnology, Inc.

patents and their non-U.S.

Pharmaceutical compositions of LB-100 prodrugs or analogs are covered

11,236,102, 10,532,050, 10,023,587, 8,822,461, 8,227,473 and 7,998,957, which are solely owned by Lixte Biotechnology,

These patents and their non-U.S.

counterparts are projected to expire in 2034, 2030 or 2028, exclusive of any patent term extension.

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and Oxabicycloheptenes, Their Preparation and Use

International Filing Date

International

applications)

32 unchanged sentences

applications)

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 use.

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

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

have developed two series of pharmacologically active drugs, designated as 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 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.

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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