LIXT US Equity☆

ITEM 1A. RISK FACTORS 16

ITEM 1B. UNRESOLVED STAFF COMMENTS 53

ITEM 1C CYBERSECURITY 53

ITEM 2. PROPERTIES 54

ITEM 3. LEGAL PROCEEDINGS 54

ITEM 4. MINE SAFETY DISCLOSURES 54

ITEM 6. RESERVED 56

ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 76

ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 76

ITEM 9A. CONTROLS AND PROCEDURES 76

ITEM 9B. OTHER INFORMATION 78

ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 78

PART III 79

ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 79

ITEM 11. EXECUTIVE COMPENSATION 84

ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 97

ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 98

INDEX TO EXHIBITS 99

CONSOLIDATED FINANCIAL STATEMENTS F-1

Introductory

Comment

Throughout

this Annual Report on Form 10-K, the terms “we,” “us,” “our,” “our company,” “Lixte,”

the “Company” and the “Registrant” refer to Lixte Biotechnology Holdings, Inc., a Delaware corporation, and Lixte

Biotechnology, Inc., a Delaware corporation, our wholly-owned subsidiary.

FORWARD-LOOKING

STATEMENTS

This

Annual Report on Form 10-K (the “Report”) contains certain forward-looking statements. For example, statements regarding

our financial position, business strategy and other plans and objectives for future operations, and assumptions and predictions about

future product demand, supply, manufacturing, costs, marketing and pricing factors are all forward-looking statements. These statements

are generally accompanied by words such as “intend,” “anticipate,” “believe,” “estimate,”

“potential(ly),” “continue,” “forecast,” “predict,” “plan,” “may,”

“will,” “could,” “would,” “should,” “expect” or the negative of such terms

or other comparable terminology. We believe that the assumptions and expectations reflected in such forward-looking statements are reasonable,

based on information available to us on the date hereof, but we cannot assure you that these assumptions and expectations will prove

to have been correct or that we will take any action that we may presently be planning. However, these forward-looking statements are

inherently subject to known and unknown risks and uncertainties. Actual results or experience may differ materially from those expected

or anticipated in the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited

to, regulatory policies, competition from other similar businesses, and market and general policies, competition from other similar businesses,

and market and general economic factors. This discussion should be read in conjunction with the consolidated financial statements and

notes thereto included in this Report.

If

one or more of these or other risks or uncertainties materialize, or if our underlying assumptions prove to be incorrect, actual results

may vary materially from what we project. Any forward-looking statement you read in this Report reflects our current views with respect

to future events and is subject to these and other risks, uncertainties and assumptions relating to our operations, results of operations,

growth strategy, and liquidity. All subsequent forward-looking statements attributable to us or individuals acting on our behalf are

expressly qualified in their entirety by this paragraph. You should specifically consider the factors identified in this Report, which

would cause actual results to differ before making an investment decision. We are under no duty to update any of these forward-looking

statements after the date of this Report or to conform these statements to actual results.

PART

I

ITEM

1. BUSINESS

Company

Overview

The

Company is a clinical-stage biopharmaceutical company focused on identifying new targets for cancer drug development and developing and

commercializing cancer therapies. The Company’s product pipeline is primarily focused on inhibitors of protein phosphatase 2A,

which is used to enhance cytotoxic agents, radiation, immune checkpoint blockers and other cancer therapies. The Company believes that

inhibitors of protein phosphatases have significant therapeutic potential for a broad range of cancers. The Company is focusing on the

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

activity.

The

Company believes that the mechanism by which LB-100 affects cancer cell growth is different from cancer agents currently approved for

clinical use. LB-100 is currently being tested in clinical trials in Ovarian Clear Cell Carcinoma, Metastatic Micro Satellite Stable

(MSS) Colon Cancer, and Advanced Soft Tissue Sarcoma. LB-100 has shown anti-cancer activity in animal models of glioblastoma multiforme,

neuroblastoma, and medulloblastoma, all cancers of neural tissue. LB-100 has also been shown to enhance the effectiveness of commonly

used anti-cancer drugs in animal models of melanoma, breast cancer and sarcoma. 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, LB-100 will improve therapeutic benefit.

As

a compound moves through the FDA-approval process, it becomes an increasingly valuable property, but at a cost of additional investment

at each stage. As the potential effectiveness of LB-100 has been documented at the clinical trial level, the Company has allocated resources

to expand the breadth and depth of its patent portfolio. The Company’s approach has been to operate with a minimum of overhead,

moving compounds forward as efficiently and inexpensively as possible, and to raise funds to support each of these stages as certain

milestones are reached. The Company’s longer-term objective is to secure one or more strategic partnerships or licensing agreements

with pharmaceutical companies with major programs in cancer.

The

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

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 access to equity capital to fund its

operating requirements.

Description

of Business

Most

cancer patients are treated with either chemotherapy or immunotherapy or both. These therapies often have limited benefit and there is

a high unmet medical need to enhance their effects. In many preclinical models we have shown that LB-100 enhances the effect of both

chemotherapy and Immunotherapy

LB-100,

a small molecule potent inhibitor of PP2A, was designed and developed by us. Numerous preclinical studies have documented that LB-100

potentiates most if not all anti-cancer drugs that damage DNA. LB-100 is not associated with any increase in cytotoxicity when given

with cytotoxic drugs. This synergy involves transient interruption of several DNA damage repair pathways by LB-100 and an increase in

cell division rate. LB-100 has FDA Investigational New Drug status in the US and Investigational Medicinal Product Dossier approval in

the European Union.

In

its initial Phase 1 clinical trial, LB-100 given alone daily for 3 days was non-toxic, except for a transient increase in serum creatinine

believed to be caused by inhibition of PP2A in the renal tubules. In the Phase 1 clinical trial, the Maximum Tolerated Dose (“MTD”)

was 2.33mg/m2 daily for 3 days every 3 weeks. Of the 25 patients with heavily-treated advanced solid tumors with measurable disease,

3 patients had stable disease for 2 cycles, 3 patients had stable disease for 4 cycles, and 3 patients had stable disease for 6 cycles.

One patient with pancreatic cancer had a partial response after 12 cycles lasting 534 days.

Low

doses of LB-100 have now been shown to enhance immune checkpoint inhibition (“ICI”) by several different mechanisms affecting

the tumor compartment and immune T-cell compartment. LB-100 increases CD8+T-cell infiltration and CD8-Treg ratio, CD8+T-cell proliferation,

and cytokine production induces microsatellite instability, neoantigen production and immune responsiveness, converting immunologically

“cold” to “hot” cancers.

Ovarian

clear cell carcinoma patients with inactivating mutations in PPP2R1A, a gene coding for a scaffold component of PP2A, and treated with

immune checkpoint inhibitors, were recently found to have markedly longer survival than patients without the mutation in their cancers.

Retrospective reviews of patients with a variety of cancers treated with ICI or chemotherapy show much longer survival of ICI-treated

patients with a PPP2R1A mutation in their tumors.

Based

on the observations in ovarian clear cell carcinoma, we have initiated a clinical trial in this disease combining LB-100 with a monoclonal

antibody blocking PD-1, a protein found on T-cells (NCT06065462).

Given

these preclinical and clinical observations, it is likely that LB-100 may be a general way to enhance immunotherapy responses.

The

research on the LB-100 series was initiated in 2006 under a Cooperative Research and Development Agreement (“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.

We

have also designed and developed the LB-200 series, which consists of histone deacetylase inhibitors (HDACi). LB-200 has not 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 preclinical

development of our LB-200 series of compounds at this time.

Clinical

Trial Agreements

Spanish

Sarcoma Group Collaboration Agreement

Effective

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 with respect to 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 improvement in survival 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.

GEIS

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 is to enter approximately 150 to 170 patients in this clinical trial over a period of

two to four years. The Phase 1 portion of the study began in the quarter ended June 30, 2023 to determine the recommended Phase 2 dose

of the combination of doxorubicin and LB-100. As advanced sarcoma is a very aggressive disease, the design of the Phase 2 portion 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 approximately 50% of the 102 events required for final analysis is reached.

On

October 13, 2022, we 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, our lead clinical compound, plus doxorubicin,

versus doxorubicin alone, the global standard for initial treatment of advanced soft tissue sarcomas (ASTS). Consequently, this clinical

trial commenced during the quarter ended June 30, 2023 and to be completed and a report prepared by December 31, 2026. In April 2023,

GEIS completed its first site initiation visit in preparation for the clinical trial at Fundación Jiménez Díaz University

Hospital (Madrid). Up to 170 patents will be entered into the clinical trial. The recruitment phase of the Phase 1b portion of the protocol

was completed during the quarter ended September 30, 2024. We expect to have data on toxicity and preliminary efficacy from this portion

of the clinical trial during the quarter ending December 31, 2025.

Given

the focus on the combination of LB-100 with immunotherapy in ovarian clear cell carcinoma and colorectal cancer and the availability

of capital resources, the Company entered into Amendment No. 1 to the Collaboration Agreement effective March 11, 2025 that relieved

the Company of the financial obligation to support the randomized Phase 2 portion of the clinical trial contemplated in the Collaboration

Agreement of approximately $3,095,000. As a result, it is uncertain as to whether the Phase 2 portion of this clinical trial will proceed.

Clinical

Research Support Agreement Relating to Small Cell Lung Cancer

We

had executed a Clinical Research Support Agreement with the City of Hope National Medical Center to carry out a Phase 1b clinical trial

of LB-100 combined with an FDA-approved standard regiment for treatment of untreated extensive-stage disease small cell lung cancer.

The clinical trial was initiated on March 9, 2021. However, due to the lack of patient accrual, the Company provided notice to the City

of Hope National Medical Center of the Company’s intent to terminate the Clinical Research Support Agreement effective as of July

8, 2024.

MD

Anderson Cancer Center Clinical Trial

On

September 20, 2023, we announced an investigator-initiated Phase 1b/2 collaborative clinical trial to assess whether adding LB-100 to

a human programmed death receptor-1 (“PD-1”) blocking antibody of GSK plc (“GSK”), dostarlimab-gxly, may enhance

the effectiveness of immunotherapy in the treatment of ovarian clear cell carcinoma (“OCCC”). The clinical trial is being

sponsored by The University of Texas MD Anderson Cancer Center (“MD Anderson”) and is being conducted at The University of

Texas - MD Anderson Cancer Center. We are providing LB-100 and GSK is providing dostarlimab-gxly and financial support for the clinical

trial. On January 29, 2024, we announced the entry of the first patient into this clinical trial. We currently expect that this clinical

trial will be completed by December 31, 2027.

On

February 25, 2025, we announced that we had added the Robert H. Lurie Comprehensive Cancer Center (Lurie Cancer Center) of Northwestern

University as a second site in a clinical trial combining the Company’s proprietary compound LB-100 with GSK’s dostarlimab

to treat ovarian clear cell cancer. Patient recruitment is underway, and the first patient has been dosed.

Netherlands

Cancer Institute Clinical Trial

Effective

June 10, 2024, we entered into a Clinical Trial Agreement with the Netherlands Cancer Institute (“NKI”) to conduct a Phase

1b clinical trial of the Company’s protein phosphatase inhibitor, LB-100, combined with atezolizumab, a PD-L1 inhibitor, the proprietary

molecule of F. Hoffman-La Roche Ltd. (“Roche”), for patients with microsatellite stable metastatic colon cancer. Under the

agreement, we will provide our lead clinical compound, LB-100, and under a separate agreement between NKI and Roche, Roche will provide

atezolizumab and financial support for the clinical trial. We have no obligation to and will not provide any reimbursement of clinical

trial costs. Pursuant to the agreement and the protocol set forth in the agreement, the clinical trial will be conducted by NKI at NKI’s

site in Amsterdam by principal investigator Neeltje Steeghs, MD, PhD, and NKI will be responsible for the recruitment of patients. The

agreement provides for the protection of the respective intellectual property rights of each of Lixte, NKI and Roche.

This

Phase 1b clinical trial will evaluate safety, optimal dose and preliminary efficacy of LB-100 combined with atezolizumab for the treatment

of patients with metastatic microsatellite stable colorectal cancer. Immunotherapy using monoclonal antibodies like atezolizumab can

enhance the body’s immune response against cancer and hinder tumor growth and spread. LB-100 has been found to improve the effectiveness

of anticancer drugs in killing cancer cells by inhibiting a protein called PP2A on cell surfaces. Blocking PP2A increases stress signals

in tumor cells expressing the PP2A protein. Accordingly, combining atezolizumab with LB-100 may enhance treatment efficacy for metastatic

colorectal cancer, as cancer cells with heightened stress signals are more vulnerable to immunotherapy.

This

study comprises a dose escalation phase and a dose expansion phase. The objective of the dose escalation phase is to determine the recommended

Phase 2 dose (RP2D) of LB-100 when combined with the standard dosage of atezolizumab. The dose expansion phase will further investigate

the preliminary efficacy, safety, tolerability, and pharmacokinetics/dynamics of the LB-100 and atezolizumab combination. The clinical

trial opened in August 2024 with the enrollment of the first patient. Patient accrual is expected to take up to 24 months, with a maximum

of 37 patients with advanced colorectal cancer to be enrolled in this study.

The

principal investigator of the colorectal study testing LB-100 in combination with atezolizumab is currently investigating two Serious

Adverse Events (“SAEs”) observed in the clinical trial that was launched in August 2024. The Investigational Review Board

(IRB) of the Netherlands Cancer Institute has requested additional information with respect to these SAEs and the study has been paused

for enrollment until the IRB’s questions have been, as more fully discussed at “Item 7. Management’s Discussion and

Analysis of Financial Condition and Results of Operations – Specific Risks Associated with the Company’s Business Activities

– Serious Adverse Events”.

National

Cancer Institute Pharmacologic Clinical Trial

In

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

Primary

malignant brain tumors (gliomas) are very challenging to treat. Radiation combined with the chemotherapeutic drug temozolomide has been

the mainstay of therapy of the most aggressive gliomas (glioblastoma multiforme or GBM) for decades, with little further benefit gained

by the addition of one or more anti-cancer drugs, but without major advances in overall survival for the majority of patients. In animal

models of GBM, the Company’s novel protein phosphatase inhibitor, LB-100, has been found to enhance 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 was not known. Many drugs potentially

useful for GBM treatment do not enter the brain in amounts necessary for anti-cancer action.

The

NCI study was designed to determine the extent to which LB-100 enters recurrent malignant gliomas. Patients having surgery to remove

one or more tumors received one dose of LB-100 prior to surgery and had blood and tumor tissue analyzed to determine the amount of LB-100

present and to determine whether the cells in the tumors showed the biochemical changes expected to be present if LB-100 reached its

molecular target. As a result of the innovative design of the NCI study, it was believed that data from a few patients would 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. Blood and brain tumor tissue were analyzed from seven patients after intravenous infusion of a single dose of LB-100.

Results of the investigation demonstrated that there was virtually no entry of LB-100 into the brain tumor tissue. Accordingly, alternative

methods of drug delivery will be required to determine if LB-100 has meaningful clinical anti-cancer activity against glioblastoma multiforme

and other aggressive brain tumors.

Patent

and License Agreements

National

Institute of Health

Effective

February 23, 2024, we entered into a Patent License Agreement (the “License Agreement”) with the National Institute of Neurological

Disorders and Stroke (“NINDS”) and the National Cancer Institute (“NCI”), each an institute or center of the

National Institute of Health (“NIH”). Pursuant to the License Agreement, we have licensed exclusively NIH’s intellectual

property rights claimed for a Cooperative Research and Development Agreement (“CRADA”) subject invention co-developed with

the Company, and the licensed field of use, which focuses on promoting anti-cancer activity alone, or in combination with standard anti-cancer

drugs. The scope of this clinical research extends to checkpoint inhibitors, immunotherapy, and radiation for the treatment of cancer.

The License Agreement is effective, and shall extend, on a licensed product, licensed process, and country basis, until the expiration

of the last-to-expire valid claim of the jointly owned licensed patent rights in each such country in the licensed territory, unless

sooner terminated.

The

License Agreement contemplates that we will seek to work with pharmaceutical companies and clinical trial sites (including comprehensive

cancer centers) to initiate clinical trials within timeframes that will meet certain benchmarks. Data from the clinical trials will be

the subject of various regulatory filings for marketing approval in applicable countries in the licensed territories. Subject to the

receipt of marketing approval, we would be expected to commercialize the licensed products in markets where regulatory approval has been

obtained.

Other

Significant Agreements and Contracts

Netherlands

Cancer Institute

On

October 8, 2021, we 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,

for a term of three years. The Development Collaboration Agreement was subsequently modified by Amendment No. 1 thereto.

The

Development Collaboration Agreement is a preclinical study intended 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. We agreed to fund the preclinical study, at an approximate cost of 391,000 Euros and provide a sufficient

supply of LB-100 to conduct the preclinical study.

On

October 3, 2023, we entered into Amendment No. 2 to the Development Collaboration Agreement with NKI, which provides for additional research

activities, extends the termination date of the Development Collaboration Agreement by two years to October 8, 2026, and added 500,000

Euros to the operating budget being funded by us.

On

October 4, 2024, we entered into Amendment No. 3 to the Development Collaboration Agreement with NKI, which suspended Amendment No. 2

and provided for a new study term of one year and starts upon the dosing of the first patient in the clinical trial at a project cost

of 100,000 Euros.

Effective

as of June 15, 2022, Dr. René Bernards was appointed to our Board of Directors as an independent director. Dr. Bernards is a leader

in the field of molecular carcinogenesis and is employed by NKI.

Intellectual

Property

Our

intellectual property includes proprietary know-how, proprietary methodologies and extensive clinical validation data and publications.

To provide legal protection of our intellectual property, we rely on a combination of patents, licenses, trade secrets, trademarks, confidentiality

and non-disclosure clauses and agreements, and other forms of intellectual property protection to define and protect our rights to our

products.

Our

products are expected to be covered by our patents. These patents now cover sole rights to the composition and synthesis of our LB-100

series of drugs, which is the Company’s lead clinical compound in development. Lixte has filed patent applications covering the

treatment of cancer with LB-100. Lixte has also filed joint patent applications with the NIH and the Netherlands Cancer Institute for

the treatment of cancer using LB-100 in combination with other drugs like immune checkpoint inhibitors and WEE1 inhibitors (a class of

drugs that target and inhibit the WEE1 kinase enzyme that plays a crucial role in regulating cell division).

Patent

applications for the LB-100 series (oxabicycloheptanes and oxabicycloheptenes) 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, and by the European Patent Office

The

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, which are owned solely by our wholly-owned

Delaware subsidiary, Lixte Biotechnology, Inc., except in several instances jointly with one of many 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.

The

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

important technology, inventions and know-how related to its business; defend and enforce its patents; preserve the confidentiality of

its trade secrets; and operate without infringing valid and enforceable patents or proprietary rights of third parties. The Company’s

ability to stop third parties from making, using, selling, offering to sell, or importing our technology may depend on the extent to

which the Company has rights under valid and enforceable licenses, patents, or trade secrets that cover these activities. In some cases,

enforcement of these rights may depend on cooperation of the joint owners of our jointly owned patents and patent applications.

With

respect to both the Company’s solely and jointly owned intellectual property, the Company cannot be sure that patents will be granted

on any of its pending patent applications or on any patent applications filed solely or jointly by the Company in the future; we cannot

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 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.

The

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 March 10, 2025, followed by a detailed listing of U.S. and non-U.S. patents that have 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.

LB-100.

The Company’s lead compound LB-100 is covered by U.S. Patent Nos. 8,822,461 and 7,998,957, which are solely owned by Lixte Biotechnology,

Inc. These patents are projected to expire in 2030 or 2028, exclusive of any available patent term extension. Counterpart non-U.S. patents

are projected to expire in 2028. Pharmaceutical compositions of LB-100 are covered by U.S. Patent Nos. 10,532,050, 10,023,587 and 8,822,461,

which are solely owned by Lixte Biotechnology, Inc. These patents and their non-U.S. counterparts are projected to expire in 2034 or

2028, exclusive of any available patent term extension.

LB-100

Combination Therapy with a Checkpoint Inhibitor. LB-100 combination therapy with a checkpoint inhibitor for treating cancer is

covered by U.S. Patent No. 12,168,008 and a pending U.S. patent application, as well as 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.

LB-100

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. and non-U.S. 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.

LB-100

Combination Therapy with Another Investigational Compound. LB-100 combination therapy with one of several other investigational

compounds for treating cancer, or preventing, inhibiting or reducing risk of metastasis of cancer, is covered by pending U.S. and non-U.S.

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.

LB-100

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. Patent No. 9,079,917, which is solely owned by Lixte Biotechnology,

Inc. LB-100 for treating glioblastoma multiforme, medulloblastoma, ovarian cancer, kidney cancer and colorectal cancer is covered by

U.S. Patent No. 10,399,993. These patents and their non-U.S. counterparts are projected to expire in 2028, exclusive of any patent term

extension.

LB-100

Prodrugs and Analogs. LB-100 prodrugs and analogs are covered by U.S. Patent Nos. 11,866,444, 10,618,908, 10,364,252, 9,988,394,

8,822,461, 8,541,458, 8,426,444, 8,227,473 and 7,998,957, which are solely owned by Lixte Biotechnology, Inc. These patents and their

non-U.S. counterparts are projected to expire in 2036, 2030 or 2028, exclusive of any patent term extension. Pharmaceutical compositions

of LB-100 prodrugs or analogs are covered by U.S. Patent Nos. 11,931,354, 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. These patents and their non-U.S. counterparts are projected to expire

in 2034, 2030 or 2028, exclusive of any patent term extension.

Our

portfolio of solely or jointly owned U.S. and non-U.S. issued patents is summarized below. We have additional U.S. and non-U.S. patent

applications pending.

Oxabicycloheptanes

and Oxabicycloheptenes, Their Preparation and Use

Patent Issue/Grant Date Expiration Date

1EP

2124550 validated and pending in Germany, Spain, France, United Kingdom and Italy

Formulations

of Oxabicycloheptanes and Oxabicycloheptenes

Patent Issue/Grant Date Expiration Date

1EP

2983661 validated and pending as Unitary Patent, and in Spain, United Kingdom and Switzerland

Process

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

Patent Issue/Grant Date Expiration Date

Oxabicycloheptane

Prodrugs

Patent Issue/Grant Date Expiration Date

1EP

3294287 validated and pending in Austria, Switzerland, Czechia, Germany, Denmark, Spain, France, United Kingdom, Hungary, Ireland, Italy,

Netherlands, and Sweden

2EP

3736275 validated and pending as Unitary Patent, and in Spain, United Kingdom and Switzerland

Oxabicycloheptanes

for Modulation of Immune Response

Patent Issue/Grant Date Expiration Date

1EP

3551629 validated and pending in Belgium, Germany, Denmark, Spain, France, United Kingdom, Ireland, Iceland, Italy, Netherlands, Norway,

Sweden and Switzerland

The

Market

Anti-Cancer

Drugs

We

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

approved for clinical use. Lead compounds of the LB-100 series have activity against a broad spectrum of common and rarer human cancers

in cell culture systems. In addition, lead compounds of the LB-100 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 commonly-used 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, LB-100

will improve therapeutic benefit without unacceptable toxicity in humans.

LB-100

is part of a pioneering effort in an entirely new field of cancer biology – activation lethality – that is advancing a new

treatment paradigm. The Company is the only company that has a drug in clinical trials with demonstrated capacity to over-activate oncogenic

signaling. The pre-clinical data obtained with LB-100 were recently posted online in a paper titled “Paradoxical Activation of

Oncogenic Signaling as a Cancer Treatment Strategy” in the scientific journal Cancer Discovery, and were published in the

July 2024 issue of Cancer Discovery. This study showed that LB-100 triggers hyper-activation of the signals that are responsible

for the deregulated proliferation of cancer cells, thus leading to cell death. This approach is the opposite of most of the current generation

of cancer therapies and opens potentially new treatment strategies.

Marketing

Plan

Our

primary goal to date has been to take our primary compound, LB-100, through Phase 2 clinical trials evaluating whether LB-100 will enhance

anti-cancer therapies. 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.

Product

Development

We

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.

Competition

The

life sciences industry is highly competitive and subject to rapid and profound technological change. 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 than we do. 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. Our competitors may succeed in obtaining patent protection and/or receiving

regulatory approval for commercializing products before we do. Developments by our competitors may render our product candidates obsolete

or non-competitive.

We

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.

We

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.

Our

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

If

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.

Employees

and Human Capital Resources

As

of March 14, 2025, we had two officer/employees, our Chief Executive Officer and our Chief Financial Officer, and one consultant, our

Chief Medical Officer. The Company relies to a significant extent on outside consultants and advisors with various technical skills and

expertise that the Company can draw on as necessary to conduct its research and development and clinical trial programs. We consider

our relationship with our employees to be good. Our future performance depends significantly upon the continued service of our key personnel

and our ability to attract highly skilled employees. We provide our officer/employees and consultants with opportunities for equity ownership.

Facilities

As

of March 14, 2025, we do not operate or lease any facilities. We contract out research and development activities, drug production, and

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

Government

Regulation

Our

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.

The

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

study including selecting of initial doses, plans for escalation of dose, plans for modification of dose if toxicity is encountered,

plans for monitoring the wellbeing of individuals participating in the study, and for defining and measuring, to the extent possible,

any untoward effects related to drug administration. Serious adverse effects, such as life-threatening toxicities and death, are immediately

reportable to the review body and to the FDA. To minimize risk when studying a new drug, the initial dose is well below that expected

to cause any toxicity. No more than three patients are entered at a given dose. In general, a dose is not escalated within an individual

patient. Once safety is established by the absence of toxicity or low toxicity in a group of three patients, a planned higher dose is

then evaluated in a subsequent group of three individuals and so on until dose-limiting toxicity is encountered. The dose level producing

acceptable toxicity is then selected as the dose level to be evaluated in Phase 2 trials. Thus, the goal of Phase 1 studies is to determine

the appropriate dose level for evaluation of drug efficacy in patients with cancer.

In

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.

In

addition, as we intend to market our products in international markets, we will 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.

Legal

Proceedings

The

Company may be subject to legal claims and actions from time to time as part of its business activities. We are not currently subject

to any threatened or pending lawsuits, legal claims or legal proceedings.

ITEM

1A. RISK FACTORS

The

following risk factors, together with the other information presented in this document, including the financial statements and the notes

thereto, should be considered by investors.

Risks

Related to Our Financial Resources and Capital Needs

We

are engaged in early-stage research and as such might not be successful in our efforts to develop a portfolio of commercially viable

products.

A

key element of our strategy is to develop LB-100 in combination with other anti-cancer therapies to treat cancer. We are seeking to do

so through our internal research programs or strategic partnerships. A significant portion of the research and development that we are

conducting involves new and unproven technologies. Research programs to identify new disease targets and product candidates or to develop

them require substantial technical, financial and human resources whether or not any candidates or technologies are ultimately identified

or proven successful. Our research programs might initially show promise in identifying potential product candidates, yet fail to yield

product candidates for clinical development for the following reasons:

If

we are unable to discover suitable potential product candidates, develop additional delivery technologies through internal research programs

or strategic partnerships, or in-license suitable products or delivery technologies on acceptable business terms, our business prospects

will suffer. Even if we discover additional product candidates, new clinical trials of one or more additional drug candidates may show

that these product candidates are unsafe or ineffective.

We

have incurred substantial losses since our inception and anticipate that we will continue to incur substantial and increasing losses

for the foreseeable future.

We

are a clinical-stage biopharmaceutical company that uses biomarker technology to identify enzyme targets associated with serious common

diseases and then design novel compounds to attack those threats. We do not have any products approved by a regulatory authority and

have not generated any revenue from collaboration or licensing agreements or product sales to date, and have incurred significant research,

development and other expenses related to our ongoing operations and expect to continue to incur such expenses. As a result, we have

not been profitable and have incurred significant operating losses since our inception. For the years ended December 31, 2024 and 2023,

we reported a net loss of $3,585,965 and $5,087,029, respectively. As of December 31, 2024 and 2023, we had an accumulated deficit of

$52,067,693 and $48,481,728, respectively.

We

do not expect to generate revenues for many years, if at all. We expect to continue to incur significant expenses and operating losses

for the foreseeable future. We anticipate these losses to increase as we continue to research, develop and seek regulatory approvals

for one or more of our product candidates and any additional product candidates we might acquire, and potentially begin to commercialize

product candidates that might achieve regulatory approval. We might also encounter unforeseen expenses, difficulties, complications,

delays and other unknown factors that could adversely affect our business. The size of our future net losses will depend, in part, on

the rate of future growth of our expenses and our ability to generate revenues. Our expenses will further increase as we:

● conduct clinical trials of our lead product candidate, LB-100;

● maintain, expand and protect our intellectual property portfolio; and

● add operational, financial and management information systems and personnel.

Our

independent registered public accounting firm has expressed substantial doubt about our ability to continue as a going concern.

The

Company’s consolidated financial statements have been presented on the basis that it will continue as a going concern, which contemplates

the realization of assets and satisfaction of liabilities in the normal course of business. The Company has no recurring source of revenue

and has experienced negative operating cash flows since inception, and management has determined that substantial doubt exists about

the Company’s ability to continue as a going concern. As a result, our independent registered public accounting firm has included

an explanatory paragraph in their report with respect to this uncertainty that accompanies our audited consolidated financial statements

as of and for the year ended December 31, 2024. This going concern opinion could materially limit our ability to raise additional funds

through the sale of equity securities in the future, and subsequent reports by our independent registered public accounting firm on our

consolidated financial statements may also include an explanatory paragraph with respect to our ability to continue as a going concern.

We

need significant additional financing to fund our operations and complete the development and, if approved, the commercialization of

our lead product candidate, LB-100. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our

product development programs or commercialization efforts.

We

expect that our existing cash resources as of December 31, 2024 will provide sufficient working capital resources to fund our operations,

including our clinical trial programs with respect to the development of our lead anti-cancer clinical compound LB-100, through approximately

September 30, 2025. Our existing cash resources will not be sufficient to complete development of and obtain regulatory approval for

our lead product candidate, and we will need to raise significant additional capital to be able to continue our efforts in this regard.

The Company estimates that it will need to raise additional capital to fund its operations by mid-2025, including its various clinical

trial commitments, to be able to proactively manage its current business plan during the remainder of 2025 and during 2026. In addition,

our operating plan might change as a result of many factors currently unknown to us, including possible additional clinical trials, and

we might need additional funds sooner than planned. The Company is considering various strategies and alternatives to obtain the required

additional capital.

We

expect to expend substantial resources for the foreseeable future to continue the clinical development and production of our lead product

candidate. These expenditures will include costs associated with research and development, potentially acquiring new product candidates

or technologies, conducting preclinical studies and clinical trials and potentially obtaining regulatory approvals and manufacturing

products.

Budgets

and future capital requirements depend on many factors, including:

● the costs to in-license future product candidates or technologies;

● our operating expenses; and

● the emergence of competing technologies or other adverse market developments.

Additional

funds might not be available when we need them on terms that are acceptable to us, or at all. We have no committed source of additional

capital. If adequate funds are not available to us on a timely basis, we might not be able to continue as a going concern or we might

be required to delay, limit, reduce or terminate preclinical studies, clinical trials or other development activities for our product

candidates or target indications, or delay, limit, reduce or terminate our establishment of sales and marketing capabilities or other

activities that may be necessary to commercialize our lead product candidate.

We

currently have no source of revenues. We might never generate revenues or achieve profitability.

Currently,

we do not generate any revenues from product sales or otherwise. Even if we are able to successfully achieve regulatory approval for

our lead product candidate, we do not know when we will generate revenues or become profitable, if at all. Our ability to generate revenues

from product sales and achieve profitability will depend on our ability to successfully commercialize products, including our lead product

candidate, LB-100, and any other product candidates that we might develop, in-license or acquire in the future. Our ability to generate

revenues and achieve profitability also depends on a number of additional factors, including our ability to:

● complete and submit applications to foreign regulatory authorities;

● obtain regulatory approval in territories with viable market sizes;

● set commercially viable prices for our intended product, if any;