GTBP US Equity☆

Item 1A. Risk Factors 13

Item 1B. Unresolved Staff Comments 33

Item 1C. Cybersecurity 33

Item 2. Properties 34

Item 3. Legal Proceedings 34

Item 4. Mine Safety Disclosures 35

PART II

Item 6. [Reserved] 37

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 40

Item 8. Financial Statements and Supplementary Data 41

Item 9A. Controls and Procedures 65

Item 9B. Other Information 65

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 65

PART III

Item 10. Directors, Executive Officers and Corporate Governance 66

Item 11. Executive Compensation 68

Item 14. Principal Accountant Fees and Services 74

PART IV

Item 15. Exhibits and Financial Statement Schedules 75

SUMMARY

RISK FACTORS

Our

business involves significant risks. Below is a summary of the material risks that our business faces, which makes an investment in our

securities speculative and risky. This summary does not address all these risks. These risks are more fully described below under the

heading “Risk Factors” in Part I, Item 1A of this annual report on Form 10-K. Before making investment decisions regarding

our securities, you should carefully consider these risks. The occurrence of any of the events or developments described below could

have a material adverse effect on our business, results of operations, financial condition, prospects and stock price. In such event,

the market price of our securities could decline, and you could lose all or part of your investment. In addition, there are also additional

risks not described below that are either not presently known to us or that we currently deem immaterial, and these additional risks

could also materially impair our business, operations, or market price of our common stock.

● Our intellectual property may be compromised.

PART

I

CAUTIONARY

NOTICE REGARDING FORWARD-LOOKING STATEMENTS

This

Annual Report on Form 10-K, including any documents which may be incorporated by reference into this Annual Report, contains “Forward-Looking

Statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange

Act of 1934, as amended. All statements other than statements of historical fact are “Forward-Looking Statements” for purposes

of these provisions, including our plans of operation, any projections of revenues or other financial items, any statements of the plans

and objectives of management for future operations, any statements concerning proposed new products or services, any statements regarding

future economic conditions or performance, and any statements of assumptions underlying any of the foregoing. All Forward-Looking Statements

included in this document are made as of the date hereof and are based on information available to us as of such date. We assume no obligation

to update any Forward-Looking Statement. In some cases, Forward-Looking Statements can be identified by the use of terminology such as

“may,” “will,” “expects,” “plans,” “anticipates,” “intends,”

“believes,” “estimates,” “potential,” or “continue,” or the negative thereof or other

comparable terminology. Although we believe that the expectations reflected in the Forward-Looking Statements contained herein are reasonable,

there can be no assurance that such expectations or any of the Forward-Looking Statements will prove to be correct, and actual results

could differ materially from those projected or assumed in the Forward-Looking Statements. Future financial condition and results of

operations, as well as any Forward-Looking Statements are subject to inherent risks and uncertainties, including any other factors referred

to in our press releases and reports filed with the Securities and Exchange Commission. All subsequent Forward-Looking Statements attributable

to the company or persons acting on its behalf are expressly qualified in their entirety by these cautionary statements. The factors identified below are believed to be important factors, but

not necessarily all of the important factors, that could cause actual results to differ materially from those expressed in any Forward-Looking

Statement made by us. Other factors not discussed herein could also have a material adverse effect on us. The following is a list of factors,

among others, that could cause actual results to differ materially from those contemplated by the forward-looking statements: our ability

to continue as a going concern; our early stage of development and the risk that our product candidates may never be successfully developed;

our need for additional capital and uncertainty regarding future financing; the inherent risks, costs and uncertainties of preclinical

and clinical development including delays, failures or unexpected safety or efficacy results; our limited regulatory and manufacturing

capabilities; our dependence on third parties for research, clinical trials and supply; our reliance on intellectual property and risks

related to protecting or licensing those rights; extensive and evolving regulatory requirements; potential product liability claims; risks

related to market acceptance and commercialization; volatility in the trading price and limited liquidity of our common stock, and the

risk that our failure to comply with Nasdaq listing standards could result in delisting. Additional factors

that may have a direct bearing on our operating results are described under “Risk Factors” and elsewhere in this Annual Report

on Form 10-K.

Introductory

Comment

The

corporate predecessor of GT Biopharma, Inc, Diagnostic Data, Inc., was incorporated in the state of California in 1965. Diagnostic Data,

Inc. changed its incorporation to the state of Delaware on December 21, 1972 and changed its name to DDI Pharmaceuticals, Inc. on March

11, 1985. On September 7, 1994, DDI Pharmaceuticals, Inc. merged with International BioClinical, Inc. and Bioxytech S.A. and changed

its name to OXIS International, Inc. On July 17, 2017, OXIS International, Inc. changed its name to GT Biopharma, Inc.

Throughout

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

and “our Company” refer to GT Biopharma, Inc.

The

GT Biopharma logo, TriKE®, and other trademarks or service marks of GT Biopharma, Inc. appearing in this quarterly report are the

property of the Company. This Annual Report on Form 10-K also contains registered marks, trademarks and trade names of other companies.

All other trademarks, registered marks and trade names appearing herein are the property of their respective holders.

The

Company is a clinical stage biopharmaceutical company focused on the development and commercialization of novel immune-oncology products

based on our proprietary Tri-specific Killer Engager (TriKE®), and Tetra-specific Killer Engager (Dual Targeting TriKE®) platforms.

The Company’s TriKE® and Dual Targeting TriKE® platforms generate proprietary therapeutics designed to harness and enhance

the cancer killing abilities of a patient’s own natural killer cells (NK cells).

ITEM

1. BUSINESS

We

are a clinical stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology products based

on our proprietary Tri-specific Killer Engager (“TriKE®”), and Tetra-specific Killer Engager (“Dual Targeting TriKE®”)

fusion protein immune cell engager technology platforms. Our TriKE® and Dual Targeting TriKE® platforms generate proprietary

therapeutics designed to harness and enhance the cancer killing abilities of a patient’s own natural killer cells (“NK cells”).

Once bound to an NK cell, our moieties are designed to activate the NK cell to direct it to one or more specifically targeted proteins

expressed on a specific type of cancer cell or virus infected cell, resulting in the targeted cell’s death. TriKE®s

can be designed to target any number of tumor antigens, including B7-H3, HER2, CD33 and PDL1, on hematologic malignancies or solid tumors

and do not require patient-specific customization. We believe our TriKE® and Dual Targeting TriKE® platforms that activate endogenous

NK cells are potentially safer than T-cell immunotherapy because there is less cytokine release syndrome (“CRS”) and fewer neurological

complications. Our preclinical data suggests that this is explained by the TriKE® dependent, CD16 directed, IL-15 proliferation of

NK cells, with little effect endogenous T cells.

We

are using our TriKE® platform with the intent to bring to market immuno-oncology products that can treat a range of hematologic

malignancies, solid tumors, and potentially autoimmune disorders. The platform is scalable, and we are implementing processes to produce

investigational new drug (“IND”) ready moieties in a timely manner after a specific TriKE® conceptual design. Specific drug

candidates can then be advanced into the clinic on our own or through potential collaborations with partnering companies. We believe

our TriKE®s may have the ability, if approved for marketing, to be used as both monotherapy and in combination with other standard-of-care

therapies.

Our

initial work was conducted in collaboration with the Masonic Cancer Center at the University of Minnesota under a program led by Dr.

Jeffrey Miller, Professor of Medicine, and the Interim Director at the Masonic Cancer Center. Dr. Miller, who also serves as our

Consulting Senior Medical Director, is a recognized key opinion leader in the field of NK cell and IL-15 biology and their

therapeutic potential. We have exclusive rights to the TriKE® platform and are generating additional intellectual

property for specific moieties.

Product

Pipeline

Our

current TriKE® product candidate pipeline (as of February 23, 2026) is summarized in the table below:

GTB-3550

GTB-3550

was our first TriKE® product candidate and its clinical development was suspended so that we could focus resources on

second-generation TriKEs®. GTB-3550 is a tri-specific killer engager, or TriKE, comprised of two single-chain variable fragments

(“scFv”) composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a

modified form of IL-15. We studied this anti-CD16-IL-15-anti-CD33 TriKE® in CD33 positive leukemias, a marker expressed on tumor

cells in acute myelogenous leukemia (“AML”), and myelodysplastic syndrome (“MDS”). The anti-CD33 antibody fragment in

GTB-3550 was derived from the M195 humanized anti-CD33 scFv. We believe the approval of the antibody-drug conjugate gemtuzumab

validates the targeting of CD33.

We

previously announced the interim clinical trial results for GTB-3550, which showed significantly reduced CD 33+ bone marrow blast levels

by 33.3%, 61.7%, 63.6%, 50% in Patient 5 (25 μg/kg/day), Patient 7 (50 μg/kg/day), Patient 9 (100 μg/kg/day), and Patient

11 (150 μg/kg/day), respectively. After the end of infusion, GTB-3550 and IL-15 concentrations declined rapidly with overall geometric

mean terminal phase elimination half-life (T1/2) of 2.2 and 2.52 hours, respectively. There was minimal CRS resulting from hyperactivation

of patient’s T-cell population at doses 5–150 μg/kg/day.

Despite

the positive interim clinical trial results, GTB-3550 was replaced by a more potent next-generation camelid nanobody TriKE®, GTB-3650,

that similarly targets CD33 on relapsed/refractory AML and high-risk MDS. A key difference between GTB-3550 and GTB-3650 is the incorporation

of camelid antibody technology instead of a scFv; our preclinical experience showed markedly enhanced potency of TriKEs® comprised

of camelid components. This is illustrated below by better tumor control of AML bearing animals with GTB-3650 (purple dots) compared

to GTB-3550 (blue dots). This provided the rationale for pausing further development of GTB-3550 and moving over to solely develop the

second-generation, camelid-based TriKE® platform.

Second

Generation TriKE®s Utilize Camelid Nanobody Technology

Our

goal is to be a leader in immuno-oncology therapies targeting a broad range of indications including hematological malignancies and

solid tumors. A key element of our strategy includes introducing a next-generation camelid nanobody platform. Camelid antibodies

(often referred to as nanobodies) are smaller than human immunoglobulin, consisting of two heavy chains instead of two heavy and two

light chains. These nanobodies have the potential to have greater affinity to target antigens, potentially resulting in greater

potency. We are utilizing this camelid antibody structure for all of our new TriKE® product candidates.

To

develop second generation TriKE®s, we designed a new humanized CD16 engager derived from a single-domain antibody. While scFvs consist

of a heavy and a light variable chain joined by a linker, single-domain antibodies consist of a single variable heavy chain capable of

engaging without the need of a light chain counterpart (see figure below).

These

single-domain antibodies are thought to have certain attractive features for antibody engineering, including physical stability, ability

to bind deep grooves, and increased production yields, amongst others. Pre-clinical studies demonstrated increased NK cell activation

against CD33+ targets including enhanced NK cell degranulation (% CD107a+) and IFNγ with the single-domain CD16 TriKE® (cam

16-wt15-33; GTB-3650) compared to the original TriKE® (scFv16-m 15-33; GTB-3550) (see figure below). This data was published by Dr.

Felices M et al (2020) in Cancer Immunol Res.

CD33+

HL60 Targets in Killing Assays

The

purple line represents the GTB-3650 and the blue line represents GTB-3550.

GTB-3650

GTB-3650

is a TriKE® which targets CD33 on the surface of myeloid leukemias and an agonistic camelid engager to the potent activating receptor

on NK cells, CD16. Use of this engager enhances the activity of wild type IL-15 included in GTB-3650. The TriKE® approach provides

a novel way to specifically target these tumors by leveraging NK cells, which have been shown to mediate relapse protection in this setting,

in an anti-CD33-targeted fashion. We are advancing GTB-3650 to clinical studies based on pre-clinical data showing a marked increase

in potency compared to GTB-3550, which we anticipate could lead to an enhanced efficacy signal in AML and MDS. We advanced GTB-3650 through

requisite preclinical studies and filed an IND application with the U.S. Food and Drug Administration (the “FDA”)

in December 2023. In late June 2024, the FDA cleared our IND Application for GTB-3650. We started study enrollment targeting patients

with relapsed/refractory AML and high grade MDS on January 21, 2025. This initial study is testing GTB-3650 as monotherapy testing administration

2 weeks on and two weeks off (to prevent NK cell exhaustion) for at least 2 cycles of therapy, as agreed on with the FDA.

GTB-5550

GTB-5550

is a B7-H3 targeted TriKE® which targets B7-H3 on the surface of advanced solid tumors (figure above). GTB-5550 is our first dual

camelid TriKE®. B7-H3 is expressed on a broad spectrum of solid tumor malignancies, allowing our team to target these malignancies

through GTB-5550. Pre-clinical work has shown that this molecule has NK-cell targeted activity against a variety of solid tumors, including

head and neck cancer squamous cell carcinoma (figure below), prostate cancer, breast cancer, ovarian cancer, glioblastoma, and lung cancer

(amongst others).

We

advanced GTB-5550 through requisite preclinical studies and filed an IND application with the FDA in October 2023 with a written response from the FDA in December 2023. The main question from the FDA was

regarding pre-clinical toxicology and a pivot to subcutaneous dosing. In early January 2026, the FDA cleared our IND Application for

GTB-5550. We anticipate starting study enrollment in mid-year 2026. The initial trial is designed as a basket trial for patients with

B7-H3+ solid tumors using Monday through Friday dosing (2 weeks on and 2 weeks off to prevent immune exhaustion).

GTB-7550

GTB-7550

TriKE® is a product candidate in development for the treatment of lupus and other autoimmune disorders. GTB-7550 TriKE® is a

tri-specific molecule composed of a camelid nanobody that binds the CD16 receptor on NK cells, a scFv engager against CD19 on malignant

and normal B cells, and a human IL-15 sequence between them.

Published

data shows that GTB-7550 effectively targets CD19+ malignant cell lines and primary chronic lymphocytic leukemia. Preliminary data

shows that GTB-7550 can target and eliminate normal B cells, which we are continuing to test in mice. We are currently exploring and

assessing potential manufacturers of GTB-7550.

Oncology

Markets

Acute

Myeloid Leukemia and Myelodysplastic Syndromes

AML

is a heterogeneous hematologic stem cell malignancy in adults with an incidence rate of 4.3% per 100,000 populations. The median age

at the time of diagnosis is 68 years. AML is an aggressive disease and is fatal without anti-leukemic treatment. AML is the most common

form of adult leukemia in the U.S. These patients will require frontline therapy, usually chemotherapy including cytarabine and an anthracycline,

a therapy that has not changed in over 40 years. Myelodysplastic syndromes are a heterogeneous group of myeloid neoplasms characterized

by dysplastic features of erythroid/myeloid/megakaryocytic lineages, progressive bone marrow failure, a varying percentage of blast cells,

and enhanced risk to evolve into acute myeloid leukemia. It is estimated that over 10,000 new cases of MDS are diagnosed each year and

there are minimal treatment options; other estimates have put this number higher. In addition, the incidence of MDS is rising for unknown

reasons.

B7-H3

Positive Solid Tumors

The

B7-H3 protein, which functions as a checkpoint inhibitor, has been identified in many of the most common solid tumor cancers, including

but not limited to bladder, breast, cervical, colorectal, endometrial, esophageal, gastric, glioma, kidney, liver, lung, pancreatic,

prostate, head and neck cancer, and melanoma. In recent studies, B7-H3 has been identified as a critical promoter of tumor cell proliferation,

migration, invasion, epithelial-to-mesenchymal transition, cancer stemness and drug resistance. Because this protein does not seem to

be expressed in normal cells, this makes it an attractive target for therapeutic intervention.

Manufacturing

We

do not currently own or operate manufacturing facilities for the production of clinical or commercial quantities of any of our

product candidates. We rely on third-party contract manufacturing operations, including Cytovance Biologics, Inc.

(“Cytovance”), a related party as of the year ended December 31, 2024, but not as of the year ended December 31, 2025,

to produce and/or test our compounds and expect to continue to do so to meet the preclinical and clinical requirements of our

potential product candidates as well as for our future commercial needs. We require in our manufacturing and processing agreements

that third-party product manufacturers produce intermediates, active pharmaceutical ingredients (“API”), and finished products in

accordance with the FDA’s current Good Manufacturing Practices (“cGMP”), and all other applicable laws and regulations. We

maintain confidentiality agreements with potential and existing manufacturers to protect our proprietary rights related to our drug

candidates.

Competition

The

market for therapeutic immuno-oncology products is highly competitive. Our therapeutic immuno-oncology (“IO”) development

programs face, and will continue to face, intense competition from pharmaceutical, biopharmaceutical and biotechnology companies, as

well as numerous academic and research institutions and governmental agencies engaged in drug discovery activities or funding, both in

the United States and abroad. Some of these competitors are pursuing the development of drugs and other therapies that target the same

diseases and conditions that we are targeting with our product candidates.

As

a general matter, we also face competition from many companies that are researching and developing cell therapies. Many of these companies

have financial and other resources substantially greater than ours. In addition, many of these competitors have significantly greater

experience in testing pharmaceutical and other therapeutic products, obtaining FDA and other regulatory approvals, and marketing and

selling. If we obtain regulatory approval for any of our product candidates, we also will be competing with respect to manufacturing

efficiency and marketing capabilities, areas in which we have limited or no commercial-scale experience. Mergers and acquisitions in

the pharmaceutical and biotechnology industries may result in even more resources’ being concentrated by our competitors. Competition

may increase further as a result of advances made in the commercial applicability of our technologies and greater availability of capital

for investment in these fields.

TriKE®

Patents and Trademarks

On

August 24, 2021, two patents were issued by the US Patent Office covering our pipeline of clinical and non-clinical product candidates

consisting of tri-specific killer engagers, or TriKE®s, designed to target natural killer, or NK, cells and tumor or virus

infected cells forming an immune synapse between the NK cell and the tumor cell thereby inducing NK cell activation at that site. The

patents broadly include TriKE®s that target the CD16 receptor, which includes the more potent camelid nanobody sequence,

an IL-15 activating domain, and any targeting domain.

University

of Minnesota

2023

Sponsored Research Agreement

On

May 20, 2024, the Company entered into a sponsored research agreement (the “2023 Sponsored Research Agreement”) with the

Regents of the University of Minnesota (the “University of Minnesota”), effective July 1, 2023. Payments totaling approximately $1.7 million were initially due over the life of the agreement. The purpose of the agreement

was for the University of Minnesota to continue work with the Company with three major goals in mind: (1) support the

Company’s TriKE® product development and commercial GMP manufacturing efforts; (2) TriKE®

pharmacokinetics optimization in humans and investigation of effects of altering the route of administration; and (3) research and

development of TriKE® platform. The major deliverables proposed were: (1) creation of IND enabling data for

TriKE® constructs in support of the Company’s product development and commercial GMP manufacturing efforts

outside of the University of Minnesota; (2) TriKE® platform drug delivery changes to allow transition from

intravenous (IV) continuous infusion to alternative drug delivery administration (IV bolus, intraperitoneal [IP], subcutaneous [SQ])

and extended PK in humans and gain an increased understanding of changes in the patient’s native NK cell population as a

result of alteration of TriKE® administration; and (3) research and development of TriKE® platform

combination with other FDA approved (or soon to be approved) therapeutics and alterations to TriKE® platform through

formation of immune complexes. Most studies used TriKE® DNA/amino acid sequences created by the Company under

existing licensing terms.

On

June 18, 2025, the 2023 Sponsored Research Agreement was amended to expire on December 31, 2025. In addition, payments amounting to $216,000

were added bringing the total payments due over the life of the agreement to approximately $1.9 million.

The

Company recorded an expense classified as research and development of approximately $863,000 and $1,078,000, pursuant to the 2023

Sponsored Research Agreement, for the years ended December 31, 2025 and 2024, respectively.

As

of December 31, 2025, there were no outstanding commitments in relation to unbilled and unaccrued amounts from the University of Minnesota

pursuant to the 2023 Sponsored Research Agreement for services that have not yet been rendered as of December 31, 2025.

2016

Exclusive Patent License Agreement

Effective

July 18, 2016, the Company entered into an exclusive patent license agreement with the University of Minnesota (as amended,

the “2016 Exclusive Patent License Agreement”), to further develop and commercialize cancer therapies using TriKE®

technology developed by researchers at the University of Minnesota to target NK cells to cancer. Under the terms of the agreement, the

Company receives exclusive rights to conduct research and to develop, make, use, sell, and import TriKE® technology worldwide

for the treatment of any disease, state, or condition in humans. The Company is responsible for obtaining all permits, licenses, authorizations,

registrations, and regulatory approvals required or granted by any governmental authority anywhere in the world that is responsible for

the regulation of products such as the TriKE® technology, including without limitation the FDA and the European Agency

for the Evaluation of Medicinal Products in the European Union. The agreement requires an upfront payment of $200,000, and license maintenance

fees of $200,000 for years 2017 through 2020, and $100,000 per year beginning in year 2021 and each year thereafter. The agreement also

includes 4% royalty fees on the net sales of licensed products, not to exceed 6% under subsequent license agreements or amendments to

this agreement, and minimum royalty payments due upon the commencement of commercial sales of licensed product is $250,000 beginning

in 2022, $2 million beginning in 2025, and $5 million beginning in 2027 throughout the remainder of the term. The agreement also includes

numerous performance milestone payments including clinical development milestone payments totaling $3.1 million, and one-time sales milestone

payments of $1 million upon reaching $250 million in cumulative gross sales, and $5 million upon reaching $500 million in cumulative

gross sales of licensed products.

Effective

May 13, 2024, the Company entered into an amended and restated exclusive patent license agreement with the University of Minnesota (the “A&R 2016 Exclusive Patent License Agreement”).

The amendment requires an upfront payment of $145,000 and amends the license maintenance fees to $50,000 in 2025, and $100,000 per

year beginning in year 2026 and each year thereafter. The amendment also includes 1% to 5% royalty fees on the net sales of licensed

products, not to exceed 6% under subsequent license agreements or amendments, and minimum royalty payments due upon the commencement

of commercial sales of licensed product is $250,000 in year one, $2 million in years two through five, and $5 million in year six

throughout the remainder of the term. The amendment also includes numerous performance milestone payments including clinical

development milestone payments totaling $3.1 million, and one-time sales milestone, and one-time sales milestone payments of $1

million upon reaching $250 million in cumulative gross sales, and $5 million upon reaching $500 million in cumulative gross sales of

licensed products.

The

Company recorded an expense classified as research and development of $50,000 and $145,000, pursuant to the A&R 2016 Exclusive

Patent License Agreement, for the years ended December 31, 2025 and 2024, respectively.

2021

Exclusive License Agreement

Effective

March 26, 2021, the Company entered into an exclusive license agreement with the University of Minnesota (the “2021 Exclusive

Patent License Agreement”), specific to the B7H3 targeted TriKE®. The agreement requires an upfront payment of

$20,000, and license maintenance fees of $5,000 per year beginning in year 2022 and each year thereafter. The agreement also

includes 2.5% to 5% royalty fees on the net sales of licensed products, and minimum royalty payments due upon the commencement of

commercial sales of licensed product of $250,000 in year one though four, and $2 million beginning in year five and throughout the

remainder of the term. The agreement also includes numerous performance milestone payments including clinical development milestone

payments totaling $3.1 million, and one-time sales milestone payments of $1 million upon reaching $250 million in cumulative gross

sales, and $5 million upon reaching $500 million in cumulative gross sales of licensed products. There is no double payment

intended; if one of the milestone payments has been paid under the A&R 2016 Exclusive Patent License Agreement no

further payment is due for the corresponding milestone.

The

Company recorded an expense classified as research and development of $5,000 and $0, pursuant to the 2021 Exclusive License Agreement,

for years ended December 31, 2025 and 2024, respectively.

2024

GTB-3650 Clinical Trial Agreement

On

November 18, 2024, the Company entered into an investigator initiated clinical trial agreement (the “2024 Clinical Trial

Agreement”) with the University of Minnesota, pursuant to which, the University of Minnesota shall sponsor an IND application

for IND 165546 GTB-3650 (the “Research Program”) and shall serve as a sponsor investigator for a phase 1 clinical trial

entitled, “GTB-3650 (CD16/IL-15/CD33) Tri-Specific Killer Engager (TriKE) for the Treatment of High Risk Myelodysplastic

Syndromes (MDS), Refractory/Relapsed Acute Myeloid Leukemia (AML), and Minimal Residual Disease in AML,” designed by the

University of Minnesota (the “Study”). The Research Program is being conducted for clinical research use. The budget for

the Study, including without limitations, funding and resources, provides for up to approximately $2 million over the course of

three years borne by the Company. The Study data will be owned by the University of Minnesota, however, the Company may use the

Study data subject to any applicable signed informed consent documents and authorization forms, applicable law and terms of the 2024

Clinical Trial Agreement. The University of Minnesota and the Company will each have the right to publish the Study results. The

2024 Clinical Trial Agreement may be terminated by the Company or the University of Minnesota at any time upon thirty days’

written notice to the other party, by the University of Minnesota immediately for health, welfare and safety reasons, or by either

party if the other party materially breaches the 2024 Clinical Trial Agreement, provided that the breaching party fails to cure such

breach within thirty days.

The

Company recorded an expense classified as research and development of approximately $750,000 and $190,000, pursuant to the 2024 Clinical

Trial Agreement, for the years ended December 31, 2025 and 2024, respectively.

As

of December 31, 2025, the Company’s commitments in relation to unbilled and unaccrued amounts from the University of Minnesota

pursuant to the 2024 Clinical Trial Agreement for services that have not yet been rendered as of December 31, 2025, amounted to approximately

$1.1 million.

Common

Stock (February 2024 Reverse Stock-Split)

On

February 2, 2024, the Company effectuated a reverse stock-split of its common stock, at a ratio of 1 for

30. The Company’s common stock began trading on a reverse stock-split-adjusted basis on The Nasdaq Capital Market on February 5,

2024, under the existing trading symbol “GTBP.”

As

a result of the reverse stock-split, every thirty (30) shares of issued and outstanding common stock were automatically combined into

one issued and outstanding share of common stock, without any change in the par value per share. The reverse stock-split reduced the number of shares of common stock outstanding on the effective date of the reverse stock-split from

41,419,000 shares to 1,380,633 shares, subject to minor adjustments due to the treatment of fractional shares.

Proportionate

adjustments were made to the per share exercise price and the number of shares of common stock that could be purchased upon exercise

of outstanding stock options and warrants for the Company’s common stock, and to the number of shares of common stock reserved

for future issuance pursuant to the Company’s 2022 Omnibus Incentive Plan.

All

share and per share information within this report have been adjusted to retroactively reflect the reverse stock-split as of the earliest

period presented.

The Committed Equity Facility

On May 14, 2025, the Company entered into the common

shares purchase agreement (as amended, the “Common Shares Purchase Agreement”) with Bristol Capital, LLC, a Delaware limited

liability company (“Bristol”), and Five Narrow Lane, L.P., a Delaware limited partnership (“5NL”), relating to

a committed equity facility (the “Committed Equity Facility”), whereby we have the right from time to time at our option to

sell to the Facility Investors (as defined below) up to $20 million of our common stock subject to certain conditions and limitations

set forth in the Common Shares Purchase Agreement. Bristol subsequently assigned all of its all of its right, title, interest and obligations

in the Common Shares Purchase Agreement to its affiliate, Hailstone Peak Funding, LLC, a Delaware limited liability company (“Hailstone,”

and together with 5NL, the “Facility Investors”). Sales of the shares of common stock to the Facility Investors under the

Common Shares Purchase Agreement, and the timing of any sales, are determined by the Company from time to time in its sole discretion

and depend on a variety of factors, including, among other things, market conditions, the trading price of the common stock and determinations

by the Company regarding the use of proceeds of such shares of common stock. The net proceeds from any sales under the Common Shares Purchase

Agreement will depend on the frequency with, and prices at, which the shares of common stock are sold to the Facility Investors. The purchase

price of the shares of common stock that the Company elects to sell to the Facility Investors pursuant to the Common Shares Purchase Agreement

are equal to 93% of the volume weighted average price of the shares of Common Stock during the applicable purchase date on which the Company

has timely delivered written notice to the Facility Investors directing it to purchase shares of common stock under the Common Shares

Purchase Agreement.

Employees

and Human Capital Resources

At

the date of this Annual Report, we have one full-time employee and numerous consultants to carry on our operations. Many of our activities

are outsourced to consultants who provide services to us on a project basis. As business activities require and capital resources permit,

we will hire additional employees and consultants to fulfill our Company’s needs.

Available

Information

We

post our annual report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and any amendments to those reports

filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act, free of charge, on the Investors section of our public website

(www.gtbiopharma.com) as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC .

In addition, you can read our SEC filings over the Internet at the SEC’s website at www.sec.gov. The contents of these websites

are not incorporated into this annual report on Form 10-K. Further, our references to the URLs for these websites are intended to be

inactive textual references only.

ITEM

1A. RISK FACTORS

Investing

in our common stock involves a high degree of risk. You should carefully consider the risks and uncertainties described below in addition

to the other information contained in this Annual Report on Form 10-K before deciding whether to invest in shares of our common stock.

If any of the following risks actually occur, our business, financial condition or operating results could be harmed. In that case, the

trading price of our common stock could decline and you may lose part or all of your investment. In the opinion of management, the risks

discussed below represent the material risks known to the company. Additional risks and uncertainties not currently known to us or that

we currently deem immaterial may also impair our business, financial condition and operating results and adversely affect the market

price of our common stock.

Risks

Related to Our Financial Condition and Capital Requirements

Our

financial condition raises substantial doubt as to our ability to continue as a going concern.

As

of December 31, 2025, we had approximately $6.9 million in cash and cash equivalents and restricted cash, and a working capital of approximately

$5.8 million, and we have incurred and expect to continue to incur significant costs in pursuit of our drug candidates. For

the year ended December 31, 2025, we recorded a net loss of approximately $28.4 million and used cash in operations of approximately

$12.9 million. Our financial statements for the year ended December 31, 2025 have been prepared assuming that we will continue

to operate as a going concern, which contemplates the realization of assets and the satisfaction of liabilities in the normal course

of business. To date, we have not generated substantial product revenues from our activities and have incurred substantial operating

losses. We expect that we will continue to generate substantial operating losses for the foreseeable future until we complete development

and approval of our product candidates. We expect to continue to fund our operations primarily through utilization of our current financial

resources and additional raises of capital.

These

conditions raise substantial doubt about our ability to continue as a going concern. In addition, the Company’s independent registered public

accounting firm, in its report on the Company’s December 31, 2025 financial statements, raised substantial doubt about the Company’s

ability to continue as a going concern. The Company has evaluated the significance of the

uncertainty regarding the Company’s financial condition in relation to its ability to meet its obligations, which has raised substantial

doubt about the Company’s ability to continue as a going concern. While it is very difficult to estimate the Company’s future

liquidity requirements, the Company believes if it is unable to obtain additional financing, existing cash resources will not be sufficient

to enable it to fund the anticipated level of operations through one year from the date the accompanying financial statements are issued.

There can be no assurances that the Company will be able to secure additional financing on acceptable terms or that it will provide us

with sufficient funds to meet our objectives. In the event the Company does not secure additional financing, the Company will be forced

to delay, reduce, or eliminate some or all of its discretionary spending, which could adversely affect the Company’s business prospects,

ability to meet long-term liquidity needs and the ability to continue operations.

Our

business is at an early stage of development and we may not develop therapeutic products that can be commercialized.

Our

business is at an early stage of development. We do not have immune-oncology products in late-stage clinical trials. We are still in

the early stages of identifying and conducting research on potential therapeutic products. Our potential therapeutic products will require

significant research and development and pre-clinical and clinical testing prior to regulatory approval in the United States and other

countries. We may not be able to obtain regulatory approvals, enter clinical trials for any of our product candidates, or commercialize

any products for years, if at all. Our product candidates may prove to have undesirable and unintended side effects or other characteristics

adversely affecting their safety, efficacy or cost effectiveness that could prevent or limit their use. Any product using any of our

technology may fail to provide the intended therapeutic benefits or achieve therapeutic benefits equal to or better than the standard

of treatment at the time of testing or production.

We

have a history of operating losses and we expect to continue to incur losses for the foreseeable future and we may never generate revenue

or achieve profitability.

During

the year ended December 31, 2025, the Company reported a net loss of approximately $28.4 million and as of December 31, 2025, and had

an accumulated deficit of approximately $724 million. We have not generated any revenue to date and are not profitable, and have incurred

losses in each year since our inception. We do not expect to generate any product sales or royalty revenues for the foreseeable future.

We expect to continue to incur significant additional operating losses for the foreseeable future as we expand research and development

and clinical trial efforts.

Our

ability to achieve long-term profitability is dependent upon obtaining regulatory approvals for our products and successfully commercializing

our products alone or with third parties. However, our operations may not be profitable even if any of our products under development

are successfully developed and produced and thereafter commercialized. Even if we achieve profitability in the future, we may not be

able to sustain profitability in subsequent periods.

Even

if we succeed in commercializing one or more of our product candidates, we expect to continue to incur substantial research and development

and other expenditures to develop and market additional product candidates. 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 revenue. Our prior losses and expected future losses have had and

will continue to have an adverse effect on our stockholders’ equity and working capital.

We

will need additional capital to conduct our operations and develop our products, and our ability to obtain the necessary funding is uncertain.

We

have used a significant amount of cash since inception to finance the continued development and testing of our product candidates, and

we expect to need substantial additional capital resources to develop our product candidates going forward and launch and commercialize

any product candidates for which we receive regulatory approval.

We

may not be successful in generating and/or maintaining operating cash flow, and the timing of our capital expenditures and other expenditures

may not result in cash sufficient to sustain our operations through the commercialization of our product candidates. If financing is

not sufficient and additional financing is not available or available only on terms that are detrimental to our long-term survival, it

could have a material adverse effect on our ability to continue to operate. The timing and degree of any future capital requirements

will depend on many factors, including:

● scientific and clinical progress in our research and development programs;

● our progress with pre-clinical development and clinical trials;

● the time and costs involved in obtaining regulatory approvals;

● the number and type of product candidates that we pursue.

Additional

financing through strategic collaborations, public or private equity or debt financings or other financing sources may not be available

on acceptable terms, or at all. Additional equity financing could result in significant dilution to our stockholders, and any debt financings

will likely involve covenants restricting our business activities. Further, if we obtain additional funds through arrangements with collaborative

partners, these arrangements may require us to relinquish rights to some of our technologies, product candidates or products that we

would otherwise seek to develop and commercialize on our own.

If

sufficient capital is not available, we may be required to delay, reduce the scope of or eliminate one or more of our research or product

development initiatives, any of which could have a material adverse effect on our financial condition or business prospects. In addition,

we may seek additional capital due to favorable market conditions or strategic considerations even if we believe we have sufficient funds

for our current or future operating plans. Attempting to secure additional financing our product candidates.

Our

research and development costs could exceed our projections requiring us to significantly modify our planned operations.

The

actual cost of our research and development programs could differ significantly from our current projections if we change our planned

development process. In the event that actual costs of our clinical program, or any of our other ongoing research activities, are significantly

higher than our current estimates, we may be required to significantly modify our planned level of operations.

The

successful development of any product candidate is highly uncertain. It is difficult to reasonably estimate or know the nature, timing

and costs of the efforts necessary to complete the development of, or the period in which material net cash inflows are expected to commence

from any product candidate, due to the numerous risks and uncertainties associated with developing drugs. Any failure to complete any

stage of the development of products in a timely manner could have a material adverse effect on our operations, financial position and

liquidity.

Risks

Related to Clinical Development and Potential Regulatory Approval

We

have limited clinical testing and regulatory capabilities, and human clinical trials are subject to extensive regulatory requirements,

which are very expensive, time-consuming and difficult to design and implement. Our products may fail to achieve necessary safety and

efficacy endpoints during clinical trials, which may limit our ability to generate revenues from therapeutic products.

We

cannot assure that we will be able to invest or develop resources for clinical trials successfully or as expediently as necessary. In

particular, human clinical trials can be very expensive and difficult to design and implement, in part because they are subject to rigorous

regulatory requirements. The clinical trial process is time consuming. We estimate that clinical trials of our product candidates will

take at least several years to complete. Furthermore, failure can occur at any stage of the trials, and we could encounter problems that

cause us to abandon or repeat clinical trials. The commencement and completion of clinical trials may be affected by several factors,

including:

● unforeseen safety issues;

● determination of dosing issues;

● inability to demonstrate effectiveness during clinical trials;

● slower than expected rates of patient recruitment;

● inability to monitor patients adequately during or after treatment; and

In

addition, we or the FDA, may suspend our clinical trials at any time if it appears that we are exposing participants to unacceptable

health risks or if the FDA finds deficiencies in our investigational new drug application, or IND, submissions or the conduct of these

trials.

Clinical

drug development is costly, time-consuming and uncertain, and we may suffer setbacks in our clinical development program that could harm

our business.

Clinical

drug development for our product candidates is costly, time-consuming and uncertain. Our product candidates are in various stages of

development and while we expect that clinical trials for these product candidates will continue for several years, such trials may take

significantly longer than expected to complete. In addition, we, the FDA, an Institutional Review Board (“IRB”), or other

regulatory authorities, including state and local agencies and counterpart agencies in foreign countries, may suspend, delay, require

modifications to or terminate our clinical trials at any time, for various reasons, including:

● difficulty in retaining subjects and volunteers in clinical trials;

● inability to add a sufficient number of clinical trial sites;

● uncertainty regarding proper formulation and dosing;

● scheduling conflicts with participating clinicians and clinical institutions;

● failure to design appropriate clinical trial protocols;

● changes in applicable laws, regulations and regulatory policies.

It

may take longer to complete our clinical trials than we project, or we may not be able to complete them at all.

For

budgeting and planning purposes, we have projected the date for the commencement, continuation and completion of our various clinical

trials. However, a number of factors, including scheduling conflicts with participating clinicians and clinical institutions, and difficulties

in identifying and enrolling patients who meet trial eligibility criteria, may cause significant delays. We may not commence or complete

clinical trials involving any of our products as projected or may not conduct them successfully.

We

expect to rely on medical institutions, academic institutions or clinical research organizations to conduct, supervise or monitor some

or all aspects of clinical trials involving our products. We will have less control over the timing and other aspects of these clinical

trials than if we conducted them entirely on our own. If we fail to commence or complete, or experience delays in, any of our planned

clinical trials, our stock price and our ability to conduct our business as currently planned could be harmed.

If

we experience delays or difficulties in the enrollment of patients in clinical trials, those clinical trials could take longer than expected

to complete and our receipt of necessary regulatory approvals could be delayed or prevented.

We

may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient

number of eligible patients to participate in these trials as required by the FDA, or similar regulatory authorities outside the United

States. In particular, because we are focused on patients with molecularly defined cancers, our pool of suitable patients may be smaller

and more selective and our ability to enroll a sufficient number of suitable patients may be limited or take longer than anticipated.

In addition, some of our competitors have ongoing clinical trials for product candidates that treat the same indications as our product

candidates, and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’

product candidates.

Patient

enrollment for any of our clinical trials may also be affected by other factors, including without limitation:

● the severity of the disease under investigation;

● the eligibility criteria for the study in question;

● the perceived risks and benefits of the product candidate under study;

● the extent of the efforts to facilitate timely enrollment in clinical trials;

● the patient referral practices of physicians;

● the ability to monitor patients adequately during and after treatment; and

Our

inability to enroll a sufficient number of patients for our clinical trials would result in significant delays and could require us to

abandon one or more clinical trials altogether. Enrollment delays in our clinical trials may result in increased development costs for

our product candidates, and we may not have or be able to obtain sufficient cash to fund such increased costs when needed, which could

result in the further delay or termination of the trial.

Consistent

with our general product development strategy, we intend to design future trials for our product candidates to include some patients

with the applicable clinical characteristics, stage of therapy, molecular alterations, biomarkers, and/or cell surface antigens that

determine therapeutic options, or are indicators of the disease, with a view to assessing possible early evidence of potential therapeutic

effect. If we are unable to locate and include such patients in those trials, then our ability to make those early assessments and to

seek participation in FDA expedited review and approval programs, including breakthrough therapy and fast track designation, or otherwise

to seek to accelerate clinical development and regulatory timelines, could be compromised.

We

are subject to extensive regulation, which can be costly and time consuming and can subject us to unanticipated delays. Even if we obtain

regulatory approval for some of our products, those products may still face regulatory difficulties.

All

of our potential products, processing and manufacturing activities, are subject to comprehensive regulation by the FDA in the United

States and by comparable authorities in other countries. The process of obtaining FDA and other required regulatory approvals, including

foreign approvals, is expensive and often takes many years and can vary substantially based upon the type, complexity and novelty of

the products involved. In addition, regulatory agencies may lack experience with our technologies and products, which may lengthen the

regulatory review process, increase our development costs and delay or prevent their commercialization.

If

we violate regulatory requirements at any stage, whether before or after we obtain marketing approval, the FDA may take enforcement action(s)

against us, which could include issuing a warning or untitled letter, placing a clinical hold on an ongoing clinical trial, product seizure,

enjoining our operations, refusal to consider our applications for pre-market approval, refusal of an investigational new drug application,

fines, or even civil or criminal liability, any of which could materially harm our reputation and financial results. Additionally, we

may not be able to obtain the labeling claims necessary or desirable for the promotion of our products. We may also be required to undertake

post marketing trials to provide additional evidence of safety and effectiveness. In addition, if we or others identify side effects

after any of our adoptive therapies are on the market, or if manufacturing problems occur, regulators may withdraw their approval and

reformulations, additional clinical trials, changes in labeling of our products, and additional marketing applications may be required.

Any

of the following factors, among others, could cause regulatory approval for our product candidates to be delayed, limited or denied:

Any