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Item 1. Business

2026-03-31 compared with 2025-03-28 · 397 added, 483 removed, 596 unchanged (60% of the section changed)

HCW Biologics Inc.

(“HCWB” or the “Company”) is a clinical-stage biopharmaceutical company developing proprietary immunotherapies to treat diseases promoted by chronic inflammation, especially age-related and senescence-associated diseases.

Our immunotherapeutics represent a new class of drug that we believe has the potential to fundamentally change the treatment of cancer and many other diseases and conditions that are promoted by chronic inflammation — and in doing so, improve patients’ quality of life and possibly extend longevity.

While chronic inflammation is possible at any age, it is more common as we age.

In this case, the condition is known as inflammaging.

The induction and retention of low-grade inflammation in an aging human body is mainly the result of the accumulation of non-proliferative but metabolically active senescent cells, which can also be caused by persistent activation of immune cells.

Chronic inflammation, including inflammaging, is believed to be a significant contributing factor to the cause for senescence-associated diseases and conditions that diminish health span, including many types of cancer, autoimmune diseases, and neurodegenerative diseases, as well as indications that impact quality-of-life that are not life-threatening.

(“HCW Biologics” or the “Company”) is a clinical-stage biopharmaceutical company developing transformative fusion immunotherapeutics to support or treat diseases promoted by chronic inflammation.

We have created novel compounds that represent a new class of drugs that we believe have the potential to fundamentally change the treatment of autoimmune disorders and other proinflammatory diseases, cancer and senescence-associated dysplasia.

Among other things, we have begun commercialization of certain commercial-ready proprietary compounds for use as reagents in the production of immunotherapeutics for the treatment of infectious diseases and cancer.

We want our products to improve patients’ healthspan as well as their quality of life, and possibly extend longevity.

Chronic inflammation is believed to be a significant contributing factor to the cause for many diseases and conditions that diminish health span and quality of life.

The induction and retention of low-grade inflammation in the human body is mainly the result of persistent activation of immune cells and the accumulation of non-proliferative but metabolically active senescent cells.

Senescence is a physiologic process important in promoting wound healing, tissue homeostasis, regeneration, embryogenesis, fibrosis regulation, and tumorigenesis suppression.

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Unresolved activation of immune cells leads to chronic low-grade inflammation, which perpetuates this cycle.

Studies have shown that strategies to reduce or eliminate senescent cells can delay, prevent, and improve age-related dysfunctions, including cancer.

Unfortunately, to date, there has been limited clinical success in targeting senescent cell accumulation or aberrant inflammasome activity using small molecule-based approaches.

Preclinical research and preliminary results from first-in-human clinical trials indicate that our immunotherapeutic approach may achieve success for cancer indications, and many other age-related diseases and conditions.

We believe our lead product candidates represent a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic drugs for the treatment of age-related diseases.

The Company has developed two different drug discovery and development platforms, our legacy TOBI (Tissue factOr-Based fusIon) platform and our newly developed targeted platform technology – the T-cell Receptor β Chain constant region (“TRBC”) platform:

• The TOBI platform is designed to engineer multi-functional fusion protein molecules and protein complexes.

Two of the Company’s proprietary molecules, HCW9201 and HCW9206, are commercial-ready to be used as reagents in the production of immunotherapeutic treatments.

On March 13, 2026, Science Advances, a peer-reviewed, high-impact journal, released a publication with the Company’s data that showed the Company’s proprietary, commercial-ready compound, HCW9206, could fundamentally change how CAR-T cell therapies are manufactured and potentially improve how they perform against diseases such as cancer and HIV.

These findings support the Company’s belief that HCW9206 is a leap forward in both clinical potential and manufacturing efficiency.

The Company has developed two proprietary drug discovery and development platforms which we use to create novel fusion immunotherapeutics:

The TOBI (Tissue factOr-Based fusIon) platform.

The TOBI TM platform is designed to engineer multi-functional fusion protein molecules and protein complexes that rebalance the immune system.

It employs a Tissue Factor (“TF”) scaffold that can be packaged with multiple protein targets, including cytokines, chemokines, ligands, receptors, and single-chain antibodies.

• The Company invented its second-generation platform, the TRBC platform, to create novel immunotherapeutics designed to treat diseases, including cancer, as well as improve quality-of-life conditions.

The immunotherapeutics created using the TRBC platform include multi-specific cytokines, targeted second-generation immune checkpoint inhibitors, and immune-cell engagers, which have the capabilities to activate subsets of immune cells that specifically target cancerous or infected cells.

As of July 13, 2024, the Company, Dr.

Wong, Altor BioScience, LLC, NantCell, Inc.

and ImmunityBio, Inc.

(collectively, Altor BioScience, LLC, NantCell, Inc.

and ImmunityBio Inc.

will be referred to herein as “ImmunityBio”), entered into a Settlement Agreement that is described in Part I, Item 3.

– “Legal Proceedings” below.

The Settlement Agreement eliminated the uncertainty of the outcome of the previously disclosed Arbitration proceedings and provided clarity for the future direction and emphasis of our clinical development strategy.

The settlement involved intellectual property the Company developed based on our proprietary TOBI TM drug discovery platform and its unique Tissue-Factor scaffold used to create protein-fusion molecules.

Our clinical development program is based on a few select lead product candidates which will be evaluated in Company-sponsored clinical trials in autoimmune disorders, solid tumors and quality-of-life conditions.

We have a large portfolio of non-core programs and assets and, for these, we anticipate that clinical development will be conducted through licensing agreements and other business development transactions.

The T-cell Receptor β Chain constant region (“TRBC”) platform.

The TRBC platform is designed to engineer multi-function fusion protein molecules and protein complexes that rejuvenate the immune system.

It employs a protein-based scaffold that can be packaged with multiple elements, including multi-specific cytokines, immune checkpoint inhibitors, and immune-cell engagers.

Our clinical development programs are based on a few select lead product candidates which will be advanced in Company-sponsored clinical trials or in partnership with a corporate partner.

Our clinical development and financing strategy consider business development transactions as a key component for our plans to develop breakthrough therapeutics.

We regularly assess our product portfolio to determine if clinical development through a corporate partnership is the optimal means to advance clinical development and commercialization.

Lead Product Candidates in Clinical Development

• HCW9302 is a clinical-stage compound that is an injectable, first-in-kind interleukin 2 (“IL-2”) fusion protein complex constructed using the Company’s proprietary TOBI platform technology.

Its mechanism of action involves binding to IL-2αβγ receptors predominantly expressed on regulatory T (“T reg ”) cells, thereby activating and expanding T reg cells that can suppress unwanted immune and inflammatory responses.

Beijing Trimmune Biotech Co., Ltd.

(“Trimmune”) has an option to license the rights to the China market for HCW9302.

On November 17, 2025, the first patient was dosed at The Ohio State University Wexner Medical Center for the Company-sponsored, multi-center first-in-human clinical trial to evaluate HCW9302 in patients with alopecia areata (NCT07049328).

• HCW11-018b is a preclinical molecule that is a novel, tetra-valent T-Cell engager we call the Big BiTE, since it consists of a BiTE (common for all T-Cell Engagers) and an Enhancer (which makes the HCWB T-Cell Engager the “BIG BiTE”).

HCW11-018b is designed to address key challenges for first generation T-Cell Engagers:

manufacturability, preclinical safety profile, and ability to treat solid tumors.

• HCW11-040 is a preclinical molecule that is a unique combination of cytokines and pembrolizumab, a generic form of Keytruda®, in a multi-functional fusion molecule.

This lead product candidate exhibits the ability to expand Tpex cells without a cytokine storm in preclinical studies.

In addition, it exhibits superior immune-cell activation, expansion, and cytotoxicity against cancer cells and tumors when compared to pembrolizumab in in-vitro and in-vivo studies.

Programs being Developed through Corporate Partnership

• HCW11-006 is a preclinical molecule that combines several different immune functional domains as part of a group of compounds characterized as multi-functional immune cell stimulators.

This lead product candidate will be developed in partnership with Trimmune, the licensee responsible for the development and commercialization of HCW11-006.

HCW11-006 will be developed by Trimmune, our licensee with exclusive worldwide rights for in vivo applications of this compound.

Trimmune intends to begin Phase 1 clinical trials in China in mid-2027.

The Company has an Opt-In Right for the Americas market that we may choose to exercise, based on the results of the first Phase 1 studies in China.

We will continue to monitor the results of IND-enabling studies and results of the clinical study before making a decision on whether to exercise our Opt-In Right.

Commercial-Ready Reagents for Production of Immunotherapeutic Treatments

• HCW9206 is a proprietary fusion protein designed as a reagent to use in the production of CAR-therapies for the treatment of infectious diseases, including HIV, and cancer.

HCW9206 is a novel class of immunotherapeutic that enables a single molecule to deliver synergistic signals from three different immune-stimulatory cytokines.

• HCW9201 is a proprietary fusion protein designed as a reagent to use in the production of Natural Killer (“NK”) cell-based therapies.

It is a unique cytokine-induced memory-like phenotype that supports enhanced anti-tumor activity, robust trafficking, superior proliferation capacity, and metabolic flexibility, all of which contribute to treatment resilience in the adverse tumor microenvironment.

HCWB has an experienced team led by Dr.

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Food and Drug Administration (“FDA”) for a bladder cancer indication in 2024.

Clinical-Stage Compounds

Novel Immunotherapeutics for T reg Expansion

HCW9302 is an injectable, first-in-kind interleukin 2 (“IL-2”) fusion protein complex constructed using the Company’s proprietary TOBI platform technology.

The FDA recently cleared us to initiate a Phase 1 clinical study using HCW9302 to treat alopecia areata.

Our strategy is to expand to other indications upon successful completion of the Phase 1 study.

HCW9302 is a fusion protein molecule that contains two IL-2 domains linked by an extracellular tissue factor domain.

IL-2 signaling is essential for homeostasis of T reg cells.

Unfortunately, recombinant IL-2 has an unfavorable pharmacokinetic profile and induces cytokine release syndrome limiting its therapeutic use.

HCW9302 provides a potential solution to this problem.

It is designed to have the therapeutic advantages of IL-2 while being well tolerated.

In our preclinical and non-human primate studies, we found that HCW9302 exhibited a longer serum half-life with an approximately 1,000-fold higher affinity for the IL2Rα than IL-2.

In addition, preclinical studies have shown HCW9302 can be administered at a dosing range that expanded and activated T reg cells but not CD4 + effector T cells.

CD4 + effector T cells (also known as helper T cells) are crucial for immune responses, but under certain conditions, their excessive activation can lead to negative effects like inflammation, tissue damage, and autoimmune reactions, particularly when they become dysregulated and target self-antigens, contributing to conditions like multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease.

We believe our preclinical studies in relevant animal models of dermatological conditions, graft rejection, atherosclerosis, diabetes, and neurodegenerative diseases as well as IND-enabling studies conducted in non-human primates support the clinical development of HCW9302 as a potential therapeutic agent for treatment of autoimmune and proinflammatory diseases.

HCW9201 + HCW9206:

Novel Immunotherapeutic for Memory-Like Natural Killer Cell

On December 24, 2020, the Company entered into an exclusive worldwide license with Wugen, Inc.

(“Wugen”) for ex vivo rights for two of its proprietary molecules.

Wugen is evaluating natural killer (“NK”) cell therapy generated using HCW9206 in combination with HCW9201 in clinical trials in cancer indications.

HCW9206 has a unique design consisting of a multi-functional compound constructed with three powerful cytokines:

IL-7, IL-15, and IL-21.

It is designed to stimulate T cell proliferation and activation, enhance NK cell cytotoxicity, and improve overall immune surveillance against pathogens or tumors.

HCW9201 + HCW9206, known as WU-NK-101, is Wugen’s lead memory NK cell therapy product and is comprised of cells optimized for anti-cancer function.

WU-NK-101 cells possess a unique cytokine-induced memory-like phenotype that supports enhanced anti-tumor activity, robust trafficking, superior proliferation capacity, and metabolic flexibility, all of which contribute to treatment resilience in the adverse tumor microenvironment.

Wugen is currently evaluating WU-NK-101 in a Phase 1 open-label study designed to characterize the safety, tolerability, and preliminary anti-tumor activity of WU-NK-101 in combination with cetuximab in patients with advanced and/or metastatic colorectal cancer (Cohort 1), and in patients with advanced and/or metastatic squamous cell carcinoma of head and neck (Cohort 2).

The overall study will be comprised of two phases, a Dose Escalation Phase, and a Cohort Expansion Phase.

The Company retained the in vivo rights to HCW9201 and HCW9206, as well as the manufacturing rights.

Wugen obtains clinical supply from the Company under the provisions of a development supply agreement.

Clinical-Stage Compound Awaiting Completion of Supply Agreement with ImmunityBio

Novel Bifunctional Immunotherapeutic with TGF-β Trap

HCW9218 is a clinical-stage bifunctional molecule that is designed to impact senescence by reducing senescent cells (i.e., senescent-cell-reducing effect) and eliminating the proinflammatory factors they secrete (i.e., senomorphic effect).

Subcutaneous administration of HCW9218 activates NK cells, innate lymphoid group-1, and CD8 + T cells, and neutralizes TGF-β.

In the Settlement Agreement reached with ImmunityBio on July 13, 2024, the Company agreed to transfer rights to develop HCW9218 for cancer indications to ImmunityBio.

HCW Biologics retained exclusive rights to develop treatments for all other age-related diseases other than cancer using HCW9218.

In future clinical development, we will be able to use the HCW9218 Recommended Phase 2 Dose (“RP2D”) and other learnings based on findings in the Phase 1 and Phase 1b cancer studies, which wrapped up at the beginning of 2024.

These studies include:

• A single-center Investigator-sponsored Phase 1 clinical trial was initiated in May 2022 and patient enrollment, dosing and the safety-evaluation period for this study were completed in February 2024.

In this study, the Masonic Cancer Center, University of Minnesota (“UMN”) evaluated HCW9218 in patients with solid tumor cancers that progressed after at least two lines of standard-of-care treatment.

Geller, M.D., M.S., Professor and Division Director of Gynecologic Oncology in the Department of Obstetrics, Gynecology and Women’s Health at UMN, served as a Principal Investigator of this trial.

At the time that the Phase 1 study was completed in February, over 70% of patients with ovarian cancer (5/7) showed evidence of stable disease.

• A multi-center Company-sponsored Phase 1b/2 clinical trial was initiated in October 2022 and patient enrollment, dosing and the safety-evaluation period for the Phase 1b portion of the study were completed in February 2024.

In this study, 15 patients have received at least one dose of HCW9218 and completed the 28-day safety evaluation period, with no dose-limiting toxicities (“DLTs”).

At the time that the Phase 1b portion of the study was completed in February 2024, 13% (2/15) of patients who participated in the study showed evidence of stable disease.

The Company had the non-exclusive rights to develop HCW9218 treatment for ovarian cancer in a neoadjuvant setting, based on a Phase 2 clinical study sponsored by the University of Pittsburgh Medical Center (“UPMC”).

Under the terms of the Settlement Agreement, UPMC had until year end of 2024 to launch this study, but failed to do so.

Thus, the Company terminated this study.

Under the Settlement Agreement, the Company agreed to transfer the HCW9218 master cell line to ImmunityBio.

In turn, ImmunityBio agreed to enter into a supply agreement with the Company by the end of January 2025 to ensure the Company had adequate clinical supply of HCW9218 available to carry on clinical studies.

As of the reporting date, a draft of the supply agreement has not been provided by ImmunityBio.

Until the supply agreement is in place, any plans for our further development of HCW9218 must be delayed.

Preclinical Compounds

Multi-Functional Immune Cell Stimulator

This product candidate is the subject of the exclusive worldwide license agreement the Company entered with WY Biotech Co., Ltd.

(“WY Biotech”), a China-based company specializing in the early-stage development of recombinant protein drugs and gene/cell therapies, on November 17, 2024 (the “WY Biotech License”).

Under the WY Biotech License, WY Biotech has rights to in vivo applications for HCW11-006.

The Company retains ex vivo rights.

Under the terms of the WY Biotech license agreement, the Company has an “opt-in right” for United States, Canada, Central America, and South America markets for no cost, that may be exercised after the completion of a Phase 1 trial in China.

WY Biotech is responsible for all of the costs for the Phase 1 clinical study.

HCW11-006 was constructed using the TRBC drug development platform.

It combines several different immune functional domains on our new protein scaffold platform as part of our Class I portfolio.

Our preclinical studies demonstrated that this multi-functional product candidate is highly effective at inducing CD8 + T cell and NK cell responses without triggering unwanted side effects in human immune cell and animal models.

HCW11-006 also exhibited anti-tumor efficacy in relevant solid tumor animal models.

We believe it has the potential to be one of the most potent immunostimulatory agents we have developed during our team members’ 30 years of biotech research.

Additional studies are being conducted to verify that HCW11-006 should combine well with other therapies, including immune checkpoint inhibitors, immune cell engagers, therapeutic antibodies, and CAR-T therapies, which the Company is conducting with world leaders in these areas.

The Company and collaborators intend to share their findings in a pivotal scientific paper published in a top-tier peer-reviewed journal.

Other Preclinical Programs

Our future clinical development will focus on our T-cell Receptor β Chain constant region (“TRBC”) drug discovery and development platform.

The Company has constructed over 50 compounds using the TRBC platform, which we group into three different classes, as defined by their construction and potential mechanism of action.

We are in the process of selecting lead compounds for each program, and then to determine from the compounds selected which ones we will develop on our own and those we will develop with a partner through out-licensing arrangements or other business development transactions.

The table below summarizes our preclinical programs by classes:

Preclinical TRBC-Based Molecules Drug Development Programs

Description of Programs

Multi-functional immune cell stimulators

• HCW11-006 is the selected lead product candidate for this class.

• Potent immunostimulatory agent to use in combination with standard-of-care therapy.

• Preclinical studies in human immune cells animal models demonstrate HCW11-006 is highly effective at inducing CD8 + T cell and NK cell responses without triggering unwanted side effects.

• HCW11-006 also exhibits anti-tumor efficacy in relevant solid tumor animal models.

• Prioritized for development through exclusive, worldwide license with WY Biotech.

Second-generation immune checkpoint inhibitors

• We have a group of compounds in this class and are currently assessing them in order to identify the strongest candidate for clinical development.

• Developing a second-generation Keytruda® for oncology & other senescence associated indications.

• Prioritized for in-house development.

Multi-specific targeting fusions and immune cell engagers

• Class III TRBC Molecules are second-generation immune-cell engagers capable of targeting tissue factor and other cell-surface antigens associated with diseased cells.

These drugs work by recruiting and activating T-cells or NK cells, types of white blood cell, to recognize and attack cancer cells.

• Our first compound in this class is HCW11-018, and we are collaborating with others to develop versions with different targeting capabilities.

• The size and scale of the GLP preclinical and clinical studies required for the development of Class III Molecules is more appropriate for well-capitalized Big Pharma.

• Prioritized for development through licensing with Big Pharma.

Clinical Development Strategy

Our goal is to develop transformative immunotherapies to lengthen health span by disrupting the link between cellular senescence, chronic inflammation, and age-related diseases and conditions.

Based on human-data read-out from clinical studies and extensive preclinical research, we believe that our data point toward the possibility we have created a new class of immunotherapeutics for cancer and other age-related diseases, and beyond therapies that to slow down or reverse the effects of aging itself.

We have constructed second-generation immunotherapeutics that we believe could represent a new class of drugs with the potential to fundamentally transform the treatment of diseases and conditions promoted by chronic inflammation, especially those related to aging – enhancing health span through the treatment for indications that enhance quality-of-life and extending longevity by developing treatments for indications for which there are no known cures.

The future of the Company’s clinical development will be primarily based on the molecules we have constructed with the TRBC drug development platform.

These compounds offer the potential to treat oncology, autoimmune diseases, infectious diseases, and chronic inflammatory conditions, offering broader therapeutic targets and more adaptable solutions compared to the Company’s TOBI platform.

The TRBC platform’s flexibility and capacity to bind multiple targets allow for more precise and potentially more effective treatments.

By targeting specific cell-surface antigens, these novel therapeutics can improve patient clinical outcomes, offering potential benefits across a wider range of indications.

The Company will select molecules for in-house development and those which are strong candidates to be developed with a partner through a licensing agreement.

In settling the Arbitration with ImmunityBio, the Company removed uncertainty regarding our rights to TOBI-based molecules.

With this clarity, we forged a new path for our clinical development for molecules created with the TOBI platform.

We will continue to develop HCW9302, our lead product candidate, for which the FDA recently cleared us to initiate a Phase 1 clinical study in alopecia areata.

Our strategy is to expand to other indications upon successful completion of the Phase 1 study.

We are less certain about the path forward for HCW9218, now a Phase 2 compound.

We have exclusive rights to develop HCW9218 for non-oncology indications, but due to uncertainty of clinical supply from the sole source, ImmunityBio, it might not be practical for the Company to pursue clinical development of HCW9218.

The TOBI platform will not be used to develop any new compounds for future clinical development.

Out-Licensing, Cooperative Agreements and Strategic Collaborations

We continue to pursue our strategy of out-licensing certain rights outside of our focus areas, as further discussed under “—Out-License Programs.” The Company continues to evaluate its portfolio to identify compounds which may be good candidates for licensing or other collaborations, where it will be to our advantage to leverage the expertise and financial strength of a partner in the development of a compound or market.

We signed our first out-license agreement at the end of 2020, when we entered into an exclusive worldwide license (the “Wugen License”) with Wugen, a company that specializes in cell-based therapies for cancer.

Wugen licensed limited rights to develop, manufacture, and commercialize cell-based therapy treatments for cancer based on two of our internally-developed, multi-cytokine fusion protein molecules, HCW9201 and HCW9206.

Wugen has created an off-the-shelf NK-cell treatment called WU-NK-101 based on the licensed molecules.

On November 17, 2024, HCW Biologics entered into an exclusive worldwide license agreement with WY Biotech for the rights to develop and commercialize in vivo applications of one of HCWB’s preclinical product candidates, HCW11-006.

WY Biotech Co., Ltd.

is a China-based company specializing in the early-stage development of recombinant protein drugs and gene/cell therapies.

HCW Biologics has a payment-free, milestone-free, and royalty-free option to recapture the development and commercialization rights of this molecule for in vivo applications in the United States, Canada, Central America, and South America (“Opt-in Territory”) after the conclusion of the Phase 1 clinical trial.

WY Biotech is financially responsible for all costs associated with research and development, manufacturing, clinical development, regulatory approval, and commercialization for the molecule

As reported in the Company’s Form 8-K filed with the SEC on March 19, 2025, on March 18, 2025, the Company and WY Biotech agreed to amend the WY Biotech License Agreement.

The Company has now completed extensive preclinical studies that further support our belief in the potential for HCW11-006 for both an in vivo and ex vivo therapy.

The in vivo therapy is licensed by WY Biotech, however, the Company retained all rights to the ex vivo therapy and applications as a reagent in cell-based therapy treatments, including cell-based therapies, such as CAR-T therapies.

The Company considers WY Biotech License provisions for the Opt-In Right to take over the development of HCW11-006 for the Americas markets to be an important feature of the WY Biotech License.

We believe our right to recapture this market is a potentially high value opportunity.

Further, we will be able to base our decision to opt-in on the human-data read-out from a Phase 1 clinical trial, which will mitigate our development risks and provide valuable clinical information about the potential for the indications we will use for Phase 2 clinical studies.

HCW Biologics Clinical Development Pipeline

The clinical development progress of our lead immunotherapeutic programs is summarized in the table below:

HCW Biologics Pipeline

As a result of the Settlement Agreement and Release HCWB entered into with ImmunityBio on July 13, 2024, the Company retains perpetual, exclusive worldwide rights to develop immunotherapeutic treatments based on HCW9218 for aging-related diseases other than cancer.

Our ability to continue development of HCW9218 depends on a supply agreement with ImmunityBio, who controls the master cell bank.

ImmunityBio is obligated under the terms of the Settlement Agreement to enter into a supply agreement with the Company not later than January 2025.

As of the reporting date, we have not received a draft of the supply agreement.

WY Biotech holds the exclusive worldwide license rights to HCW11-006 for in vivo applications.

Wugen holds an exclusive worldwide license for the ex vivo rights for two of our molecules, HCW9201 and HCW9206, with rights limited to the development of cell-based therapy treatments for cancer using the licensed molecules.

Wugen’s lead clinical program, WU-NK-101, is based on molecules licensed from our Company.

We have retained all other rights to HCW9201 and HCW9206, including, but not limited to, manufacturing rights and treatment based on subcutaneous injection.

Novel Immunotherapeutic for T reg Expansion

On January 28, 2025, the Company obtained clearance of its IND from the FDA to initiate a first-in-human Phase 1 dose escalation clinical trial to evaluate one of its lead drug candidates, HCW9302, in patients with moderate-to-severe alopecia areata, a common autoimmune disease in humans that currently has no curative FDA approved treatments.

This will be a Phase 1, open-label, multi-center Company-sponsored trial with competitive enrollment.

The study involves dose escalation to determine the toxicity profile of HCW9302 and to designate a dose level for the Phase 2 expansion phase, or the Recommended Phase 2 Dose (“RP2D”).

Up to five dose levels will be evaluated.

A stepped-down dose level will be provided in the event that unacceptable toxicity is encountered at the planned initial dose level.

In the first stage of the study, HCW9302 will be administered subcutaneously in a single dose.

Depending on the results of the single ascending dose stage, a multi-dose study of HCW9302 administered subcutaneously every 28 days for four consecutive treatments will be considered.

With the start of the first-in-human clinical trial for HCW9302 in alopecia areata, we are one step closer to advancing a potentially transformative immunotherapeutic treatment of autoimmune diseases.

This trial is a milestone for our Company, and the beginning of clinical development of treatments for quality-of-life indications.

While not life-threatening, alopecia areata has no cure and diminishes the quality of life for those suffering with this disease.

Existing treatments may provide some relief of symptoms, but there are often dangerous side effects.

If this Phase 1 study is successful, we intend to rapidly expand clinical development of HCW9302 in Phase 2 studies in patients with other autoimmune diseases and serious inflammatory conditions, including other dermatological conditions, graft rejection, and neurodegenerative diseases.

We believe we have an innovative strategy to treat age-related diseases.

Our unique approach is to utilize our internally-developed drug discovery platforms to create novel multi-functional immunotherapeutics to rejuvenate the immune system.

With our platform technologies, we have generated product candidates that are designed to direct the immune system against solid tumors, therapy-induced senescence and the adverse side effects triggered by existing standard-of-care treatments for solid tumors and hematological cancers.

We have developed product candidates that are designed to direct the immune system against inflammation allowing for the potential to treat a wide variety of autoimmune and proinflammatory diseases.

Our approach is to develop immunotherapies that reduce or eliminate the main drivers of chronic inflammation by addressing the underlying development and sustainment of these processes, as depicted in the image below:

The Science of Chronic Inflammation

While inflammation is part of the normal repair response for healing, when it becomes prolonged and persists, it is damaging and destructive.

Several common molecular pathways have been identified that are associated with chronic low-grade inflammation, especially common as we age.

Our view is that there are two primary underlying processes that drive chronic inflammation:

accumulation of senescent cells and persistent activation of immune cells .

Both of these processes generate pro-inflammatory factors that drive senescence.

These two elements share common mechanisms in promoting secretion of pro-inflammatory proteins and in many cases interact to drive senescence, and thus, inflammaging.

Our novel approach is to reduce senescent cells and eliminate the pro-inflammatory factors they secrete systemically through multiple pathways.

We believe our novel immunotherapeutic approach has the potential to fundamentally change the treatment of age-related diseases.

Senescent cells remain metabolically active and can influence tissue hemostasis, disease, and aging through their SASP factors.

Senescence is considered to be a physiologic process and is important in promoting wound healing, tissue homeostasis, regeneration, and regulation of fibrosis.

Senescence also plays a role in tumor suppression.

The accumulation of senescent cells, due to the aging of our immune cells, drives aging and age-related diseases and conditions.

The SASP factors can trigger chronic inflammatory responses and consequently augment chronic inflammatory conditions to promote tumor growth.

The connection between senescence and aging was initially based on the observation that senescent cells accumulate in aged tissue.

The use of transgenic models has enabled the detection of senescent cells systematically in many age-related disorders.

Studies have demonstrated that senescent cells play an adverse role in age-related disorders.

By leveraging our immunology expertise, we are developing potentially transformative immunotherapy candidates that use T reg cell expansion and senescent cell reduction to address chronic inflammation linked especially to age-related diseases.

Our approach is to develop immunotherapies that reduce or eliminate the main drivers of chronic inflammation by addressing the underlying development and sustainment of these processes.

Several common molecular pathways have been identified that are associated with chronic low-grade inflammation.

Our view is that the two primary underlying processes that drive chronic inflammation are persistent activation of immune cells and accumulation of senescent cells.

Both of these processes generate pro-inflammatory factors that are an underlying cause of disease.

While inflammation is part of the normal repair response for healing, when it becomes prolonged and persists, it is damaging and destructive.

Using our drug discovery platforms, we have created over 50 molecules, all of which can be administered by subcutaneous injection as well as used in adoptive cell therapy approaches.

These modular and tunable technologies have allowed us to generate a novel pipeline of internally developed product candidates we believe are capable of activating and targeting desired immune responses and blocking unwanted immunosuppressive activities.

Chronic Inflammation with Aging:

Inflammaging is a state of chronic inflammation believed to develop with advancing age.

Accumulation of senescent cells, along with the SASP factors they secrete, has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies.

Demographically, the world is rapidly growing older and more prone to inflammaging.

All countries face major challenges to ensure that their health and social systems are ready to make the most of this demographic shift.

According to the World Health Organization, in 2020, the number of people aged 60 years and older outnumbered children younger than 5 years.

By 2030, 1 in 6 people in the world will be aged 60 years or over.

In 2020, the population aged 60 years and over was estimated to be 1.4 billion people.

By 2050, the world’s population of people aged 60 years and older is expected to double to 2.1 billion people.

As we grow older, a series of complex changes ripple through our immune system.

Rising levels of inflammatory factors lead to unresolved, degenerative immune responses.

Mounting evidence suggests that this inflammation undermines many bodily systems, accelerates biological aging and contributes to age-related diseases, such as cancer, cardiovascular disease, diabetes, and neurodegenerative disease.

SASP Factors Secreted by Senescent Cells Trigger Chronic Inflammatory Responses

Rebalancing the Immune System:

Inflammation Promoted by Persistently Activated Immune Cells

Immune cells defend against infection or tissue injury.

If these activated immune cells persist, even in the absence of infection, they regulate the release of pro-inflammatory factors.

As inflammatory factor levels increase, this fuels a feedback cycle of inflammasome activation and leads to the persistent, low-grade body-wide inflammation associated with many diseases, such as autoimmune disorders and other proinflammatory diseases.

Rejuvenating the Immune System:

Inflammation Promoted by Senescence and SASP Factors

Cellular senescence is a biological condition resulting from the impact of stressors, such as chemotherapy, radiation, and pollutants, on human cells.

These stressors reduce natural human cell cytotoxicity, leading to the accumulation of senescent cells and SASP factors.

Considered harmful to neighboring cells, secreted SASP factors also activate a type of protein molecule called inflammasomes that accelerate the increasingly persistent cycle of inflammation.

As we age, senescent cells accumulate, and SASP factors increase, leading to low-grade, chronic inflammation and age-related diseases.

At HCW Biologics, our proprietary immunotherapy platforms rejuvenate the immune system, allowing it to reduce accumulated senescent cells and silence activated inflammasomes.

This disrupts the link between aging and chronic diseases.

Persistently Activated Immune Cells:

Inflammatory Factors They Secreted Trigger Chronic Inflammatory Responses

Immune cells defend against infection or tissue injury.

These activated immune cells persist as we age, even in the absence of infection, and regulate the release of pro-inflammatory factors.

As inflammatory factor levels increase, this fuels a feedback cycle of inflammasome activation and leads to the persistent, low-grade body-wide inflammation associated with many age-related diseases.

Considered harmful to neighboring cells, secreted SASP factors also activate proinflammatory cells that have the ability to promote a persistent cycle of inflammation that leads to disease, including cancer and other senescence-associated dysplasia.

Our proprietary immunotherapeutics rejuvenate the immune system and allow it to reduce accumulated senescent cells and silence the proinflammatory conditions promoted by SASP factors.

Our strategy includes the following key components:

Focus on diseases with no known FDA-approved treatments.

• Diseases to be targeted include cancer indications, neurodegenerative diseases as well as quality-of-life indications.

• Indications that will be included in our clinical development are promoted by chronic inflammation, especially inflammaging.

• Diseases to be targeted include autoimmune diseases and other proinflammatory diseases, cancer and senescence-associated dysplasia, such as Bronchopulmonary Dysplasia (“BPD”), the chronic lung disease occurring in newborns.

Focus on an autoimmune indication for the initial indication for clinical development for our lead product candidate, HCW9302.

• The Company received clearance of its IND from the FDA to initiate a first-in-human Phase 1 dose escalation clinical trial to evaluate one of its lead drug candidates, HCW9302, in patients with moderate-to-severe alopecia areata, a common autoimmune disease in humans that currently has no curative FDA-approved treatments.

• The Company intends to include up to five clinical sites in this study.

Negotiations with clinical sites are currently underway, and the Company estimates the lead site may open and initiate late in the second quarter of 2025 or early in the third quarter of 2025.

Once RP2D and safety is established in a successful Phase 1 study, expand to other carefully selected indications in Phase 2.

• The Company will refine potential expanded indications for Phase 2 clinical studies during Phase 1, conducting further preclinical research with support from Phase 1 clinical data from ancillary studies as well as human data read-outs.

• On November 17, 2025, the first patient was dosed at The Ohio State University Wexner Medical Center in the Company-sponsored, multi-center first-in-human clinical trial to evaluate HCW9302 in patients with alopecia areata (NCT07049328).

• Enrollment and treatment of subjects in this dose-escalation clinical trial is ongoing.

• As of December 31, 2025, the Company had two active clinical sites enrolling patients at The Ohio State University and James A.

Haley Veterans’ Hospital.

Once the Recommended Phase 2 Dose and safety are established for HCCW9302 in a successful Phase 1 study, evaluate other carefully selected indications in Phase 2.

• The Company will refine potential additional indications for Phase 2 clinical studies during Phase 1, based on the results of further preclinical research with support from Phase 1 clinical data from ancillary studies as well as human data read-outs.

• For HCW9302, we are focused on autoimmune diseases, including alopecia areata, and inflammatory conditions, such as other dermatological conditions, graft rejection, and neurodegenerative diseases.

Prepare for IND-applications for preclinical programs in 2027.

• We intend to complete IND-enabling studies and submit an IND application to evaluate HCW11-018b, our tetra-valent T-cell engager, in patients with solid tumors in the first half of 2027.

• We intend to complete IND-enabling studies and submit an IND application to evaluate HCW11-040, our second-generation immune checkpoint inhibitor, in patients with BPD in the second half of 2027.

Continue to build our relationships with leading clinical research centers.

• We believe we can reduce risks related to low patient recruitment and enrollment by continuing to build our relationships with clinical sites who specialize in indications that are being studied in clinical trials.

• We believe we can reduce risks related to potential low patient recruitment and enrollment by continuing to build our relationships with clinical sites who specialize in indications that are being studied in clinical trials.

• We intend to work with the strongest principal investigators who have a passion for the underlying science and search for breakthrough therapeutics.

These investigators tend to have gravitas at their institutions and the broader scientific and medical communities.

These investigators tend to have recognized standing at their institutions and the broader scientific and medical communities.

We find they can often be advocates for HCW Biologics and our clinical studies.

Balance clinical development of our proprietary molecules between a few in-house development programs and licensing programs with larger biotech companies and big pharma for other molecules.

• For in-house development, we will focus on HCW9302 and second-generation immune checkpoint inhibitors.

After the completion of Phase 1 studies in China, the Company may also elect to exercise our Opt-In Right per the WY Biotech License Agreement, and add HCW11-006 to our in-house development programs for the Americas market.

• We plan to begin actively seeking a partner for the development of the Company’s T-Cell Engager and other Immune Cell Engagers in Q2 2025.

• We will continually assess candidates for clinical development for licensing.

The Company has created over 50 compounds using the TRBC platform which it owns, many of which show bioactivity and potential for development for the treatment of diseases linked to inflammation and aging, such as cancer.

The Company created two novel drug discovery platforms, using two distinctly different scaffolds to anchor the composition of immunotherapeutic fusions.

This results in the creation of molecules with different mechanisms of action, which opens up different pathways for treatment of diseases promoted by chronic inflammation.

Our Proprietary T-Cell Receptor β Chain Constant Region Drug Discovery and Development Platform

HCW Biologics invented the TRBC drug discovery and development platform, a second-generation drug discovery technology platform, to create immunotherapeutics that activate immune responses and specifically target cancerous or infected cells.

With each milestone for lead product candidates, assess the optimal approach to advance clinical development or commercialization.

• We continually assess our programs to determine the optimal path for development.

Clinical development and commercialization may be accomplished with an internal program or corporate partnership.

Our Drug Discovery and Development Platforms

HCW Biologics has combined a deep understanding of disease-related immunology with expertise in advanced protein engineering to develop fusion immunotherapeutics using its two proprietary drug design and discovery platforms.

These two platforms enabled the Company to create over 50 novel immunotherapeutics which can be used to treat a wide range of disease indications.

TOBI (Tissue factOr-Based fusIon) Platform

Our TOBI (Tissue factOr-Based fusIon) Drug Discovery and Development Platform is a proprietary immunotherapeutic drug discovery and development technology which the Company used to construct multi-domain cytokine-based immunotherapeutics using a Tissue-Factor (“TF”) scaffold.

T issue fact O r- B ased fus I on Drug Discovery and Development Platform

The domains of TOBI-based molecules are discrete.

We have evaluated a TOBI-based molecule in clinical trials and have generated human data that shows that this molecule is capable of achieving the desired imm une responses against solid tumors, including ovarian and pancreatic cancer.

Based on other research, we believe that other TOBI-based molecules could activate the designed immune responses against other diseases or infected cells by blocking unwanted autoimmune / inflammatory activities.

Based on a TF scaffold, the TOBI TM platform packs multiple protein targets, including cytokines, single- chain antibodies, and ligands, into a fusion molecule.

These molecules are capable of engaging immunostimulatory functions and addressing many signaling pathways simultaneously.

Some of these fusion protein complexes have ex vivo and in vivo applications.

Moreover, the TOBI TM platform is reproducible and suitable for cGMP manufacturing.

T-Cell Receptor β Chain Constant Region (“TRBC”) Platform

Our proprietary T-Cell Receptor β Chain Constant Region (“TRBC”) Drug Discovery and Development Platform is an immunotherapeutic drug discovery and development technology that the Company used to construct fusion immunotherapeutics that activate immune responses and specifically target cancerous or infected cells.

The platform utilizes the TRBC protein as a scaffold to build multi-chain chimeric polypeptides, which include target-binding domains and affinity domains, enabling the targeting of specific antigens.

We believe these polypeptides stimulate immune cells, modulating immune functions and signaling pathways.

T-Cell Receptor β Chain Constant Region Drug Discovery and Development Platform

Molecules created with the TRBC platform integrate multiple protein targets, such as cytokines, single-chain antibodies, and ligands, into a single fusion complex designed to engage immunostimulatory functions and modulate various signaling pathways.

This flexible, adaptable platform has facilitated the development of a groundbreaking pipeline of internally developed product candidates.

This versatile scaffold enables the creation of multiple classes of immunotherapeutic compounds:

Multi-Functional Immune Cell Stimulators – Multifunctional, cytokine-based immunotherapeutic compounds.

Second-Generation Immune Checkpoint Inhibitors – Multifunctional immunotherapeutic fusions which improve the performance of immune checkpoint inhibitors.

Multi-Specific Targeting Fusions and Enhanced Immune Cell Engagers – Constructs with immune-cell engagers targeting cell-surface antigens associated with diseased cells.

T-Cell Receptor β Chain Constant Region (“ TRBC”) Drug Discovery and Development Platform

Our Proprietary Tissue factOr-Based fusIon Development Platform

Our proprietary TOBI development platform is a proprietary immunotherapeutic drug design and discovery platform which enables us to construct multi-domain cytokine-based immunotherapeutics using a Tissue-Factor (“TF”) scaffold.

The domains of TOBI-based molecules are discrete and can be “turned on” and “turned off.” We have evaluated HCW9218, a TOBI-based molecule, in two Phase 1/1b clinical trials and have generated human data that shows that this molecule is capable of achieving the desired immune responses against solid tumors, including ovarian and pancreatic cancer.

Based on a TF scaffold that serves as the “backbone” for the construction of fusion molecules, the TOBI platform packs multiple protein targets, including cytokines, single-chain antibodies, and ligands, into a fusion molecule.

These molecules are capable of engaging immunostimulatory functions and addressing many signaling pathways simultaneously.

Some of these fusion protein complexes have ex vivo as well as in vivo applications.

TOBI also provides a scalable approach for generating large-scale current Good Manufacturing Practice (“cGMP”)-grade heteromeric fusion protein complexes to support clinical applications.

The TOBI discovery platform was featured in an article authored by the Company and published in July 2021 in the peer-reviewed journal Cancer Immunology Research , “ A ‘Prime and Expand’ Strategy Using the Multifunctional Fusion Proteins to Generate Memory-Like NK cells for Cell Therapy,” Shrestha N, et al., July 2024.

The reference to our paper does not constitute incorporation by reference of the information contained in the paper.

This versatile scaffold enables the creation of multiple functional immune cell stimulators, second-generation immune checkpoint inhibitors, and second-generation immune cell engagers.

Clinical-Stage Program for Autoimmune and Proinflammatory Diseases

IL-2 Based Fusion Protein Molecules for T reg Expansion

HCW9302 is a novel fusion protein molecule that contains two IL-2 domains linked by an extracellular tissue factor domain.

IL-2 signaling is essential for homeostasis of T reg cells.

Unfortunately, recombinant IL-2 has an unfavorable pharmacokinetic profile and induces cytokine release syndrome limiting its therapeutic use.

HCW9302 provides a potential solution to this problem.

It is designed to have the therapeutic advantages of IL-2 while being well tolerated.

We are currently evaluating HCW9302 in a clinical study to verify our preclinical studies that found HCW9302 functions as a potent agent to stimulate and expand T reg cells that suppress the activity of proinflammatory cells and factors.

We have observed a long serum half-life compared with recombinant interleukin-2 (rhIL-2), a US FDA licensed drug for renal cell carcinoma and metastatic melanoma, which contributed to the ability of subcutaneously administered HCW9302 to activate and expand T reg cells in mice in a well-tolerated dose range without activating proatherogenic CD4+ T cells.

This finding also suggests that greater CD25-mediated T reg activation may be superior to “mutein”-based strategies to prevent or diminish IL-2 binding to IL-2Rβγ on effector cells.

In addition, preclinical studies have shown HCW9302 can be administered at a dosing range that expanded and activated T reg cells but not CD4+ effector T cells.

CD4+ effector T cells (also known as helper T cells) are crucial for immune responses, but under certain conditions, their excessive activation can lead to negative effects.

For information about the bi-specific TOBI fusion, HCW9302, and its effects on T reg responses in an inflammatory disease, see Frontiers in Immunology , “A Novel Interleukin-2-Based Fusion Molecule, HCW9302, Differentially Promotes Regulatory T Cell Expansion to Treat Atherosclerosis in Mice,” Zhu, X., et al., January 2023.

The reference to our paper does not constitute incorporation by reference of the information contained in the paper.

Autoimmune and Proinflammatory Diseases

HCW9302 is our leading clinical-stage drug candidate designed to address chronic inflammatory responses and associated tissue destruction typical of autoimmune disease.

Thus, we selected an autoimmune disease as the gateway indication for the clinical development of HCW9302.

HCW9302 is designed to activate and expand T reg cells, suppressing the persistently activated immune cells, inflammasome-bearing cells and their inflammatory factors.

Preclinical studies show it has a 1,000-fold higher affinity for IL2Rα than IL-2, with a longer serum half-life.

It is well tolerated, effectively expanding T reg cells without activating CD4 + effector T cells (“T eff ” cells).

In a dose toxicity study in non-human primates, we established that HCW9302 induced T reg cell proliferation and accumulation at a dose level with no observed adverse events.

For this study, HCW9302 was administered monthly via subcutaneous injection for six months.

Findings from this IND-enabling study contributed to the development of the clinical strategies for HCW9302 in autoimmune disease indications.

Alopecia Areata

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(See StatsPearls, National Library of Medicine of National Institutes of Health, National Alopecia Areata Foundation.)

Potential Phase 2 Expanded Indications

The goals of the Phase 1 clinical trial are to assess whether the safety profile is acceptable to conduct further studies and establish a RP2D that can increase T reg cells activity in patients participating in the study.

If we achieve the Phase 1 study objectives, the Company plans to progress the clinical development of HCW9302 in patients with alopecia areata as well as other autoimmune diseases and inflammatory conditions, including other dermatologic diseases, organ transplant rejection and neurodegenerative diseases.

Potential Additional Phase 2 Indications

The goals of the Phase 1 clinical trial are to assess whether the safety profile is acceptable to conduct further studies and establish a recommended phase 2 dose (“RP2D”) that can increase T reg cell activity in patients participating in the study.

If we achieve the Phase 1 study objectives, the Company plans to progress the clinical development of HCW9302 in patients with alopecia areata as well as other autoimmune diseases and inflammatory conditions, including organ transplant rejection, neurodegenerative diseases, and other dermatologic diseases, such as atopic dermatitis and vitiligo.

Organ Transplant Rejection

Through collaborative research, the Company has performed some preclinical research using HCW9302 in organ transplant rejection.

Through collaborative research, the Company has performed preclinical research using HCW9302 in organ transplant rejection.

According to the United Network for Organ Sharing, in 2025, there were a record-breaking 46,632 organ transplants performed in the United States.

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This condition involves chronic inflammation and immune responses against the transplanted graft, leading to complications and symptoms that vary depending on the transplanted organ.

United Network for Organ Sharing.)

Neurodegenerative Diseases

The Company’s preclinical work in neurodegenerative diseases to date has focused on Alzheimer’s Disease.

According to the Alzheimer’s Association, for the United States, health care and long-term care costs for people living with dementia are projected to reach $360 billion in 2024 and nearly $1 trillion in 2050.

According to the Alzheimer’s Association, for the United States, health care and long-term care costs for people living with dementia were projected to reach $384 billion in 2025 and nearly $1 trillion in 2050.

Further statistics from the Alzheimer’s Association offer a partial explanation for these staggering costs.

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• An estimated 7.2 million Americans aged 65 and older are living with Alzheimer's in 2024.

Seventy-three percent are age 75 or older.

Seventy-four percent are age 75 or older.

• Almost two-thirds of Americans with Alzheimer's are women.

• About 1 in 9 people aged 65 and older (11%) has Alzheimer's.

• Alzheimer's disease was the fifth-leading cause of death among people aged 65 and older in 2021.

• Alzheimer's disease was the sixth-leading cause of death among people aged 65 and older in 2022.

• By 2050, the number of Americans with Alzheimer’s is projected to rise to nearly 13 million.

Cancer Indications

Class II TRBC Molecules:

Second-Generation Immune Checkpoint Inhibitor

The Company is currently conducting preclinical studies in relevant animal models to identify the strongest candidate in the group of TRBC Molecules classified as second-generation immune checkpoint inhibitors.

Several immune checkpoint inhibitors have been approved for the treatment of a limited number of cancer indications.

While immune checkpoint inhibitors are considered a breakthrough therapy that has revolutionized the way cancer is treated, the response rates among patients remains stubbornly low in many of the most common cancer indications.

There are several clinical studies underway for therapeutics to be used in combination with immune checkpoint inhibitors to broaden the number of indications and improve response rates.

Our focused indications are pancreatic and ovarian cancer.

This market is dominated by a few companies, predominantly Merck & Co.

and its product, Keytruda®.

Leading immune checkpoint inhibitors face a patent cliff in the next few years.

The opportunity presented by the patent expiry of approved immune checkpoint inhibitors lies in the potential for increased competition and availability of generic or biosimilar versions of these drugs which may result in a loss of market exclusivity and revenue as competition.

It may also incentivize innovation and the development of new formulations, combinations, or delivery methods to maintain market share and competitive advantage.

Alzheimer’s Association.)

Preclinical Stage Clinical Development Programs

The Big BiTE - Tetra-Valent T-Cell Engager

HCW11-018b is a novel, tetra-valent T-Cell engager we call the Big BiTE, since it consists of a BiTE (common for all T-Cell Engagers) and an Enhancer (which makes the HCWB T-Cell Engager the “BIG BiTE”).

It is designed to address key challenges for first generation T-Cell Engagers:

manufacturability, preclinical safety profile, and ability to treat solid tumors.

In our extensive preclinical studies, it induces robust, sustained, antigen-specific tumor killing, enhances CD8⁺T-cell activation, survival, and effector functions and promotes tumor infiltration into solid tumors.

It combines a tissue factor-targeting BiTE with IL-15 immune stimulation and a TGF-β trap to overcome immunosuppression and poor T-cell infiltration of conventional BiTEs in solid tumors.

In non-human primate studies, HCW11-018b has demonstrated favorable tolerability, long serum half-life and favorable pharmacokinetics, without using the Fc fusion technology commonly found in bi-specific or tri-specific fusion molecules.

Extensive preclinical studies further show that HCW11-018b does not trigger cytokine release syndrome when administered in doses within its therapeutic window.

Cytokine release syndrome is a common, often manageable systemic inflammatory response in the current generation of BiTE antibody therapies.

IND-enabling studies are expected to be completed in first half of 2027.

Target Indications:

Pancreatic Cancer

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This cancer has the highest mortality rate of all major cancers.

In the U.S., pancreatic cancer is currently the third leading cause of cancer-related death after lung and colon and expected to become the second leading cause of cancer-related death by 2030.

In the U.S., pancreatic cancer is currently the third leading cause of cancer-related death after lung and colon and is expected to become the second leading cause of cancer-related death by 2030.

alone, an estimated 66,440 Americans were diagnosed with pancreatic cancer and more than 51,750 died from the disease in 2024.

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Survival is higher when pancreatic cancer is detected early.

Early diagnoses is difficult because there are few signs or symptoms before it has spread outside of the pancreas.

Early diagnoses is difficult because there are few signs or symptoms before the cancer has spread outside of the pancreas.

China, the United States, and Japan had the highest number of pancreatic cancer cases in 2022.

There were approximately 500,000 new cases and 470,000 deaths in 2022.

The table below shows the new cases and the ASR/100,000.

Age-standardized rates (“ASR”) are a summary measure of the rate of disease that a population would have if it had a standard age structure.

Worldwide there were approximately 550,000 new cases and 500,000 deaths in 2025.

The table below shows the number of new cases estimated in 2025.

Pancreatic Cancer

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In the United States, while ovarian cancer is the 11th most common cancer among women, it is the fifth leading cause of cancer-related death among women.

Worldwide, ovarian cancer is the seventh most common cancer in women.

It is estimated that by 2035, the incidence of ovarian cancer will increase by 55% to 371,000 worldwide, and deaths will increase by 67% to 254,000 worldwide.

For 2026, the American Cancer Society estimates an overall five-year survival of about 49%–54%.

Survival is highly stage-dependent, exceeding 90% for early-stage (localized) detection, but dropping to 30%–40% for distant, late-stage diagnosis.

Ovarian cancer is often referred to as “the silent killer” for a good reason:

It ranks as the fifth deadliest cancer among women, according to the American Cancer Society.

Overall, survival rates fall well below that for other cancers, such as breast cancer.

Treatment for ovarian cancer usually involves a combination of surgery and chemotherapy.

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This includes those with inherited gene changes like BRCA1, BRCA2, and Lynch syndrome.

Ovarian cancer survival rates vary widely.

The latest five-year survival rates largely fall between 30% and 50% and in general have begun to improve over the last 20 years.

In the United States, the relative five-year survival rate for ovarian cancer is 50.8%.

Overall, survival rates fall well below that of other cancers.

World Ovarian Cancer Coalition, American Cancer Society and Center for Disease Control and Prevention.)

Class I TRBC Molecules:

Multi-Functional Immune Cell Stimulators

Class I TRBC Molecules combine several different immune functional domains on the TRBC scaffold.

The Company has conducted preclinical studies that demonstrate that this multi-functional group of molecules is highly effective at inducing CD8 + T cell and NK cell responses without triggering unwanted side effects in human immune cells animal models.

HCW11-006 also exhibits anti-tumor efficacy in relevant solid tumor animal models.

In addition to HCW11-006, the Company is investigating various structures with different combinations of cytokines in our quest to identify lead product candidate(s) in this group of molecules.

We anticipate the completion of our efficacy assessment in mice and safety profiling in a small study in non-human primates before the end of 2025.

Results of these studies are expected to show the optimal construction for lead product candidates.

Example of Class I TRBC Molecule

Second-Generation Multi-Functional Immune Cell Stimulator

HCW11-002 is a Class I TRBC molecule that contains the same immune moieties as HCW9218, and it has demonstrated its promising capabilities in stimulating immune cells in preclinical studies.

Based on this potential, the Company is considering accelerating the development of HCW11-002 for senescence-associated indications.

Senescence-Associated Diseases

The Class I TRBC Molecules have potential for the treatment of senescence-associated indications, such as bronchopulmonary dysplasia (“BPD”), chronic deep wrinkles and senile lentigo (age spots) removal.

BPD is a form of chronic lung disease that causes long-term breathing problems in premature babies.

The condition often results in poor growth and development.

An estimated 10,000 to 15,000 babies in the United States develop BPD each year.

American Cancer Society, World Ovarian Cancer Coalition.)

Second-Generation Immune Checkpoint Inhibitor

HCW11-040 is a multifunctional fusion molecule that is a unique combination of cytokines and pembrolizumab, a generic form of Keytruda ® .

It is designed to expand progenitor T (Tpex) cells, which are the primary cells to respond to ICI therapy, without triggering cytokine storm in preclinical studies.

Tpex cells have self-renewal capabilities and are considered a primary driver for the success of ICI therapies, making them an attractive target for improving treatment outcomes.

Subcutaneous administration is expected to improve safety and quality-of-life for patients.

In preclinical studies, HCW11-040 has exhibited superior immune-cell activation, expansion, and cytotoxicity against cancer cells and tumors over Keytruda ® in in-vitro and in-vivo studies.

Further preclinical studies have been conducted in a senescence-associated dysplasia indication that have generated promising data.

Based on these results, the Company has selected Bronchopulmonary Dysplasia (“BPD”), a chronic lung disease that affects preterm infants, as the initial indication for clinical studies.

IND-enabling studies are expected to be completed in the second half of 2027.

Target Indications:

Bronchopulmonary Dysplasia and Other Senescence-Associated Dysplasia

The number of newborns suffering with Bronchopulmonary Dysplasia (“BPD”) is growing due to rising premature birth rates and improved survival rates of extremely preterm infants, particularly in infants born at 23–27 weeks gestation, affecting 10,000–15,000 babies annually in the U.S.

There is no known cure for BPD, which involves high morality and morbidities.

(See BioSpace, Bronchopulmonary Dysplasia Market Size to Reach USD 472.0 Million by 2035, Impelled by Increasing Premature Birth Rates, January 27, 2025.)

There are several quality-of-life indications which are classified as senescence-associated dysplasia.

Senile lentigo (age spots) and chronic deep wrinkles are two such conditions.

Aesthetics treatments represent a large and growing market due to the aging population.

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Global Growth Report, Fortune Business Insights.)

Class III TRBC Molecules:

Immune Cell Engagers

Class III TRBC Molecules are second-generation immune-cell engagers capable of targeting tissue factor and other cell-surface antigens associated with diseased cells.

Class III TRBC Molecules are part of a new class of therapeutic treatments based on the development of immune-cell engagers.

Among these are T-cell targeted molecules — antibodies engineered to redirect T cells to recognize and kill cancer cells — that are being developed to treat cancer and tackle issues that could potentially lead to treatment that is more effective and safer for cancer patients.

Recent deal activity indicates that the pharmaceutical industry and the biotech industry have recognized the benefits of Enhanced Immune Cell Engagers, in particular T-Cell Engagers.

Recent notable deals in the immune cell engager space include AbbVie partnering with Xilio Therapeutics to develop antibody-based immunotherapies, with AbbVie paying a significant upfront payment of $52 million;

Candid Therapeutics making multiple collaborations to discover and develop new T-cell engagers, including a deal with Nona Bioscience (“Nona”) where Nona could potentially receive up to $320 million in milestone payments;

and GSK acquiring CMG1A46, a clinical-stage dual CD19 and CD20-targeted T-cell engager from Chimagen for $300 million upfront.

Even though immune-cell engagers have great potential, there are major challenges in the clinical development.

The complexity and scale of the GLP preclinical and clinical studies required for the development of Class III Molecules is more appropriate for well-capitalized pharmaceutical companies or a larger biotech company.

Companies that undertake this challenge must deal with managing potential severe toxicities, among other obstacles.

Further complications arise from potential off-target effects and patient selection for optimal treatment outcomes.

In light of recent transactions coupled with the challenges of clinical development, we plan to take advantage of industry interest in this breakthrough drug strategy.

We intend to develop these molecules through corporate partnering and out-licensing arrangements.

Out-License Programs

Program being Co-Developed in Partnership with Trimmune

HCW11-006 is a novel fusion molecule which combines several different immune functional domains as part of a group of compounds characterized as multi-functional immune cell stimulators, which will be developed in partnership with Trimmune, the licensee responsible for the development and commercialization of HCW11-006.

Trimmune holds the exclusive worldwide rights for in vivo applications of HCW11-006.

Based on promising data seen in preclinical in-vitro and in-vivo studies conducted by HCW Biologics, Trimmune expects to initiate a Phase 1 clinical trial in China in the first half of 2027 to evaluate HCW11-006 in the treatment of solid tumors.

The Company has a payment-free, milestone-free, and royalty-free option to recapture all rights to the development and commercialization of HCW11-006 for in vivo applications in the United States, Canada, Central America, and South America (Opt-in Territory) after the conclusion of the Phase 1 clinical trial in China.

If the Company exercises the option, thereafter, HCW Biologics and Trimmune will be co-development partners.

The parties have also agreed to build unified clinical programs, and, when the HCW11-006 co-development project generates key clinical data, to actively work together in pursuing business development opportunities with multi-national corporations.

Each party will be financially responsible for all costs associated with research and development, manufacturing, clinical development, regulatory approval, and commercialization for the licensed molecule in its territory.

Therefore, expenses to complete the first Phase 1 clinical trial in China will be paid by Trimmune.

This arrangement allows the Company to have direct access to the Phase 1 results without financial responsibility for the cost.

Commercial-Ready Molecules Used As Reagents

Multi-Cytokine Protein Fusion Immunotherapeutic Reagent

HCW9206 is a commercial-ready, novel immunotherapeutic reagent engineered to deliver synergistic signaling from three immune-stimulatory cytokines within a single molecule, which provides a revolutionary approach to generate chimeric T-cell receptor - T cells (CAR-Ts) for immunotherapy with increased function in a cost-effective manner.

HCW9206, a first-in-class cytokine-scaffold-based platform, enables production of more potent CAR-T-based immunotherapies by generating a CAR-T population which is highly functional and markedly enriched for long-live T-memory stem cells (T scm ).

This strategy is broadly applicable to increase persistence and functionality of CAR-Ts, potentially enhancing their clinical efficacy for treating infectious diseases and cancer.

Treating T cells with HCW9206 can quickly and effectively produce HIV- and CD19-specific CAR-T cells that are highly enriched for the T scm memory phenotype, as well as effector T cells that have been shown in mouse models to be capable of maintaining suppression of HIV and leukemic cell proliferation.

Therefore, generating CAR-T cells through HCW9206 treatment could provide a new, improved, and highly scalable method for generating CAR-T cells to treat patients with infectious disease and cancer and replace standard CAR-T cell production using αCD3/28 activation.

This has widespread implications for the generation of more robust CAR-T cell-based immunotherapies to potentially improve CAR-T cell functional persistence and efficacy for treatment of HIV and cancer.

Cole et al., “IL-7/IL-15/IL-21 cytokine-fusion scaffold generates highly functional CAR-T cells enriched in long-live T memory stem cells,” Science Advances, 13 Mar 2026, Vol 12, Issue 11.)

Beyond CAR-T applications, HCW9206 has also been utilized to expand Cytokine-Induced Memory-Like (CIML) NK cells using a feeder cell-free “Prime and Expand” strategy ( 10.1007/s00262-024-03765-8 ).

In this approach, HCW9206 is combined with an IgG1 antibody that recognizes the scaffold domain of HCW9206, enabling CD16-mediated NK cell engagement during the expansion phase.

This cytokine- and CD16-dependent process generates CIML NK cells with enhanced metabolic fitness, stable epigenetic IFNG promoter demethylation, improved anti-tumor activity in vitro and in vivo , and superior persistence in NSG mouse models.

The platform represents a streamlined, feeder cell–free manufacturing strategy designed to support multi-dose infusion and off-the-shelf adoptive cell therapy (ACT).

Collectively, these findings position HCW9206 as a next-generation CAR-T and NK cells manufacturing reagent capable of streamlining production, reducing reliance on multi-component activation systems, and potentially lowering manufacturing costs.

By improving CAR-T functionality and durability -- long-standing challenges in the field -- HCW9206 may enhance long-term therapeutic outcomes in malignancies, chronic infections, and autoimmune diseases, while also supporting emerging in vivo CAR-T manufacturing technologies.

The GMP master cell bank and manufacturing process for HCW9206 have been established, and a Drug Master File for its use as an ex vivo reagent has been filed with the FDA.

HCW9206 is currently positioned as a commercial-ready product as a reagent for CAR-T–based manufacturing applications.

HCW Biologics holds the perpetual, exclusive worldwide license to develop immunotherapeutic treatments based on HCW9206 for all disease indications, with a Right of First Refusal to ImmunityBio for cancer indications.

Generation of CIML NK-Cells Reagent

HCW9201 is a commercial-ready, novel fusion immunotherapeutic reagent constructed with IL-12, IL-15 and IL-18 that activates and expands NK cells.

NK cells are a promising cellular therapy for cancer, with challenges in the field including persistence, functional activity, and tumor recognition.

Brief priming of blood NK cells with HCW9201 results in differentiation of memory-like NK cells, which have the potential for enhanced responses against cancer by activating and proliferating NK cells.

HCW9201 stimulation improved NK cell metabolic fitness, and resulted in the DNA methylation remodeling characteristic of memory-like differentiation.

HCW9201 increases in short-term and memory-like NK cell cytotoxicity and Interferon-Gamma production against leukemia targets.

See Shrestha et al., “A “Prime and Expand” strategy using the multifunctional fusion proteins to generate memory-like NK cells for cell therapy Cancer Immunol Immunother.

HCW9201 represents a protein engineering approach that solves many problems associated with multi-signal receptor engagement on immune cells, and HCW9201-primed NK cells will be advanced as an ideal approach for clinical GMP-grade memory-like NK cell production for cancer therapy.

In addition, the molecule has been shown to be compatible with NK cell manufacturing platforms, further supporting its versatility in immune cell therapy production.

The GMP master cell bank and manufacturing process for HCW9201 have been established, and a Drug Master File for its use as an ex vivo reagent has been filed with the FDA.

HCW9201 is currently positioned as a commercial-ready product as a regent for Cytokine Induced Memory Like (CIML) NK cells–based manufacturing applications.

HCW Biologics Pipeline

The status of our lead immunotherapeutic programs is summarized in the table below:

a) Beijing Trimmune Biotech Co., Ltd.

holds the exclusive worldwide license rights to HCW11-006 for in vivo applications.

Novel Immunotherapeutic for T reg Expansion being Evaluated in Autoimmune Disorder

On November 17, 2025, the Company initiated its first-in-human Phase 1 dose escalation clinical trial to evaluate one of its lead drug candidates, HCW9302, in patients with alopecia areata, a common autoimmune disease in humans that currently has no curative FDA approved treatments.

This trial is a Phase 1, open-label, multi-center Company-sponsored trial with competitive enrollment.

The Company currently has two active clinical sites at The Ohio State University and James A.

Haley Veterans’ Hospital.

The study involves dose escalation to determine the toxicity profile of HCW9302 and to designate a dose level for the Phase 2 expansion phase, or the Recommended Phase 2 Dose (“RP2D”).

Up to five dose levels are being evaluated.

In the first stage of the study, HCW9302 is being administered subcutaneously in a single dose.

Enrollment and treatment of subjects in this dose-escalation clinical trial is ongoing with no dose limiting toxicities reported as of March 16, 2026.

Depending on the results of the single ascending dose stage, a multi-dose study of HCW9302 administered subcutaneously every 28 days for four consecutive treatments will be considered.

This trial is a milestone for our Company, and the beginning of clinical development of treatments for quality-of-life indications.

While not life-threatening, alopecia areata has no cure and diminishes the quality of life for those suffering with this disease.

Existing treatments may provide some relief of symptoms, but there are often serious side effects.

If this Phase 1 study is successful, we intend to rapidly advance clinical development of HCW9302 in Phase 2 studies in patients with other autoimmune diseases and serious inflammatory conditions, including graft rejection, neurodegenerative diseases, and other dermatological conditions, such as atopic dermatitis and vitiligo.

Business Development and Out-License Programs

We have created over 50 immunotherapeutic molecules with our proprietary drug discovery and development platforms.

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We expect out-licensing to provide non-dilutive financing to bolster resources available to fund our core markets and programs and possibly commercialize molecules, with the hope that our licensees achieve success through our licenses.

We established our first out-license arrangement in December 2020, when the Company entered into the Wugen License, an exclusive worldwide license agreement with Wugen for rights to develop cell therapy-based treatments using two of our internally-developed fusion protein molecules and improvements thereto, including clinical-stage and preclinical stage fusion molecules, HCW9201 and HCW9206, respectively.

We believe these molecules are capable of generating highly activated cells in a short time frame and large-scale NK cell expansion without relying on feeder cells.

Wugen has exercised its right to sublicense their rights for Greater China.

As licensor, we have limited information rights to clinical data which we are required to treat as nonpublic confidential information.

As licensee, Wugen, a private company, determines when and if clinical data read-outs are disclosed to the public.

We retain manufacturing rights and other rights, including regulatory T cell-based cellular therapy and injectable rights, for licensed molecules under the terms of the Wugen License.

On June 18, 2021, we entered into a master services agreement with Wugen for the supply of materials for clinical development of licensed products.

Thereafter, each purchase transaction must be accompanied by a statement-of-work.

We plan to enter into a commercialization supply agreement when Wugen enters its commercial stage.

According to the terms of the Wugen License, Wugen will fund all future clinical development and commercialization activities for any indications utilizing the licensed molecules for cell-based therapy as covered by the Wugen License.

In addition to an upfront fee which consisted of a significant equity ownership position in Wugen’s common stock, we have the opportunity to receive additional payments for development and commercialization milestones as well as single-digit royalties.

WY Biotech Co., Ltd.

On November 17, 2024, HCW Biologics entered into an exclusive, worldwide License, Research, and Co-Development Agreement (the “WY Biotech License Agreement”) with WY Biotech Co., Ltd.

(the “WY Biotech”) for in vivo applications of one of the Company’s preclinical, proprietary molecules, HCW11-006.

Upon the completion of a Phase 1 clinical trial in any jurisdiction, the Company has an “Opt-In Right,” which gives the Company the option to assume all control and responsibility for the development, manufacture and commercialization of HCW11-006 for in vivo applications in the Opt-In Territory.

The “Opt-In Territory” is North America, South America, and Central America.

Upon the completion of the exercise of the Opt-In Right, the Company would be responsible for all costs associated with research and development, manufacturing, clinical development, regulatory approval, and commercialization for the licensed molecule in the Opt-In Territory.

As reported in the Company’s Form 8-K filed with the SEC on March 19, 2025, on March 18, 2025, the Company and WY Biotech agreed to amend the WY Biotech License Agreement.

The Company has now completed extensive preclinical studies that further support our belief in the potential for HCW11-006 for both an in vivo and ex vivo therapy.

The Company considers WY Biotech License provisions for the Opt-In Right to take over the development of HCW11-006 for the Americas markets to be an important feature of the WY Biotech License.

We believe our right to recapture this market is a potentially high value opportunity.

Wugen Exclusive Worldwide License Agreement

In December 2020, we entered into an exclusive worldwide license agreement with Wugen, under which Wugen licensed limited rights to develop, manufacture, and commercialize cell-based therapy treatments for cancer using two of our internally-developed, multi-cytokine fusion protein molecules, HCW9201 and HCW9206.

Since inception, the Company has recognized $16.2 million of revenues derived from the Wugen License, including upfront license fees in cash and shares of Wugen common stock, payments for vials of materials, and for manufacturing of development supplies for clinical trials.

The Company continues to hold the 2.2 million shares of Wugen common stock we received as consideration for the Wugen License.

These shares represent a 1.61% ownership interest in Wugen as of December 31, 2025.

In January 2026, Wugen received a Breakthrough Therapy Designation from the U.S.

Food and Drug Administration (“FDA”) for its investigational CAR-T cell therapy, Sofi-cel.

Sofi-cel is an investigational, potential first-in-class, allogeneic, anti-CD7 CAR-T cell therapy currently under evaluation in a pivotal trial (T-RRex) for patients with relapsed or refractory (R/R) T cell acute lymphoblastic leukemia or T cell lymphoblastic lymphoma (T-ALL/LBL).

Breakthrough Therapy Designation is intended to expedite the development and review of medicines for serious or life-threatening conditions with evidence of a substantial clinical improvement.

Wugen plans to submit a Biologics License Application (“BLA”) to the FDA in 2027.

This therapy holds the potential to be the first approved “off-the-shelf” CART-T for T-cell malignancies.

On May 29, 2025, the Company agreed to a request from Wugen to suspend the Wugen License, including Wugen’s clinical trial due diligence obligations and its obligation to pay up to $500,000 annually to reimburse the Company for certain research and development expenses.

The suspension will run for a period of one year from the effective date of the suspension and will end on May 29, 2026.

During the suspension, the Company has the exclusive right to seek alternate licensees and terminate the Wugen license in order to enter other business development transactions related to the ex vivo use of the licensed molecules.

Trimmune Exclusive Worldwide License Agreement

On November 17, 2025, the Company and Beijing Trimmune Biotech Co., Ltd.

(“Trimmune”) entered into an Amended and Restated License, Research and Co-Development Agreement (“Trimmune License”) following the assignment of the original License, Research and Co-Development Agreement, which includes an exclusive license to HCW11-006 for in vivo applications (“WY Biotech License”) from WY Biotech Co., Ltd.

The parties restructured the terms of the original WY Biotech License to include the assignment of rights to Trimmune and an option to license HCW9302 for in vivo applications in China or Asia.

In the Trimmune License, the parties agreed to restructure the upfront license fee to consist of a $3.5 million cash payment from which the government of China would withhold taxes which are refundable, and a transferable minority equity ownership interest in Trimmune.

In addition, the parties agreed that for additional consideration, Trimmune has an option to license the exclusive China rights to clinical development and commercialization for in vivo applications of HCW9302, the Company’s clinical-stage molecule currently being evaluated for the treatment of an autoimmune disorder.

In addition to the upfront license fee, the Company is eligible to receive additional development milestone payments and double-digit royalties on future product sales.

The Company will receive a substantial portion of the proceeds from certain future transaction(s) involving the molecule, if such a transaction(s) occur.

We also have a payment-free, milestone-free, and royalty-free option to recapture the development and commercialization rights for this molecule for the United States, Canada, Central America, and South America (Opt-in Territory) after the conclusion of the Phase 1 clinical trial in China.

Trimmune is financially responsible for all costs associated with research and development, manufacturing, clinical development, regulatory approval, and commercialization for the molecule.

Therefore, expenses to complete the first Phase 1 clinical trial in China will be paid by Trimmune.

This arrangement allows HCW Biologics to have direct access to the Phase 1 results without financial responsibility for the costs incurred prior to the time a decision must be made regarding the Opt-In Right.

In accordance with the terms of the Trimmune License, the deal closing took place upon receipt of the upfront payment.

As of March 16, 2026, the Company has received the full upfront license fee, which consisted of $3.5 million in gross proceeds, or $2.9 million net of taxes, and a transferable minority equity interest in Trimmune.

Subsequent Events.

Commercial-Ready Molecules Used as Reagents:

Active Search for Corporate Partner

As a result of the amendment to the license agreement with Wugen Inc.

(“Wugen”), the Company has an opportunity, until May 28, 2026, to enter into a new license agreement based on using HCW9206 as a reagent in the manufacture of CAR-T products.

During this time, the Company has the exclusive right to seek alternate licensees and terminate the license with Wugen in order to enter other business development transactions related to the ex vivo use of HCW9206 and HCW9201.

Both of these molecules have a GMP master cell bank and manufacturing process, as well as a Drug Master File for use as an ex vivo reagent filed with the FDA.

Manufacturing

For TOBI Molecules, we have established internally developed large scale manufacturing processes for producing these fusion molecules from Chinese hamster ovary (“CHO”) cells in a cGMP-compliant setting.

For TOBI TM molecules, we have established internally developed large scale manufacturing processes for producing these fusion molecules from Chinese hamster ovary (“CHO”) cells in a cGMP-compliant setting.

We have a long-standing relationship with a contract manufacturing organization, EirGenix, Inc.

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By the end of 2019, we successfully launched cGMP production with manufacturing runs of clinical grade materials adequate for support of our clinical trials.

As of December 31, 2024, we have successfully completed cGMP production of five of our molecules (HCW9101, HCW9201, HCW9206, HCW9218, and HCW9302).

The production campaigns include the sufficient quantities of clinical grade materials required to complete the Phase 1 / 2 clinical trials we have planned during 2025 and 2026 for HCW9302.

As of December 31, 2025, we have successfully completed cGMP production of four of our molecules (HCW9101, HCW9201, HCW9206, and HCW9302).

The production campaigns include sufficient quantities of clinical grade materials required to complete the Phase 1 or Phase 2 clinical trials we have planned for HCW9302 during 2026 and 2027.

We currently rely on EirGenix and other third-party manufacturers for the cGMP production of sufficient quantities of our drug product candidates for our clinical trials.

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On August 15, 2022, we purchased a 36,000 square foot building located in Miramar, Florida that is intended to serve as our new headquarters.

After refitting this building, we expect to have the capabilities for cGMP clinical drug manufacturing, storage, distribution, and quality testing.

We expect to relocate to this building and complete validation of the facility in the first half of 2026.

We have the flexibility to complete the buildout of the manufacturing facility on a longer schedule, should we choose to delay completion.

In the meantime, we will continue to manufacture clinical-grade material with third-party manufacturers.

After refitting this building, we expect to have the capabilities for small scale drug manufacturing, storage, distribution, and quality testing.

We expect to relocate to this building upon completion;

however, the date of completion is uncertain at this time.

Our staff has expertise in building and running cGMP manufacturing facilities for immunotherapeutics.

In addition, our manufacturing process is wholly-owned and developed by us, so we do not expect to be reliant on a third-party for manufacturing expertise or processes.

We have the flexibility to complete the buildout of the manufacturing facility on a longer schedule, should we choose to delay completion.

In the meantime, we intend to continue manufacturing clinical-grade material using third-party manufacturers.

Intellectual Property

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As with other biotechnology and pharmaceutical companies, our ability to secure and maintain intellectual property protection for our product candidates, future products, and other internally-developed technologies will depend on our success in obtaining effective patent coverage and enforcing those patents if granted.

However, we cannot guarantee that our pending patent applications, and any patent applications that we may in the future file, will result in the issuance of patents, or that any issued patents we have obtained or may obtain will provide sufficient proprietary protection from competitors.

However, we cannot guarantee that our pending patent applications, and any patent applications that we may file in the future, will result in the issuance of patents, or that any issued patents we have obtained or may obtain will provide sufficient proprietary protection from competitors.

Any issued patents that we obtain may be challenged, invalidated, or circumvented by third parties.

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Internally-Developed Intellectual Property

TOBI Platform and TOBI-Based Molecules

As of December 31, 2024, the United States Patent and Trademark Office (the “USPTO”) has granted ten patents, including fundamental patents that protect the underlying technology for our two lead product candidates, HCW9218 and HCW9302, as well as patents that protect the underlying technology and use of the molecule HCW9206, which is licensed to Wugen, conveying rights to develop cell-based therapies for cancer.

TOBI TM Platform and TOBI TM -Based Molecules

As of December 31, 2025, the United States Patent and Trademark Office (the “USPTO”) has granted fifteen patents, including fundamental patents that protect the underlying technology for our lead product candidate, HCW9302, as well as patents that protect the underlying technology and use of the molecule HCW9206, which is licensed to Wugen, conveying rights to develop cell-based therapies for cancer.

In respect of Wugen, we retain all other rights to HCW9206, including manufacturing rights.

As part of a confidential Settlement Agreement with ImmunityBio, Inc.

in 2024, the Company assigned certain patents and patent applications to ImmunityBio, Inc., yet the Company retained a world-wide exclusive license in respect of the use of TOBI molecules outside of oncology indications.

Licensed patents that protect the underlying technology for proprietary molecules include:

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• The USPTO granted U.S.

11,518,792 to HCW Biologics on December 6, 2022.

This patent contains composition claims for immunotherapeutic multi-chain chimeric polypeptides, supporting our lead drug candidate, HCW9218.

As of December 31, 2024, in addition to a license to ten issued U.S.

patents, we have a license to four issued Japanese patents, two issued Australian patents, one issued Singaporean patent, one issued Taiwanese patent, and 124 pending patent applications worldwide, including 20 pending U.S.

utility patent applications, one pending provisional U.S.

patent application, three pending Patent Cooperation Treaty (“PCT”) applications, nine Hong Kong applications, and 91 total pending non-U.S.

11,884,712 to HCW Biologics on January 30, 2024.

This patent contains compositions claims encompassing HCW9206.

As of December 31, 2025, in addition to a license to fourteen issued U.S.

patents, we have a license to seven issued Japanese patents, three issued Australian patents, one issued Singaporean patent, four issued Chinese patents, two issued European patents, two issued Israeli patents, and two New Zealand patents, and 67 pending patent applications worldwide, including 10 pending U.S.

utility patent applications, seven Hong Kong applications, and 50 total pending non-U.S.

national phase patent applications and Taiwanese patent applications.

HCW Biologics owns 13 pending patent applications worldwide including one pending U.S.

utility patent application, two pending provisional U.S.

HCW Biologics owns one issued U.S.

patent and 13 pending patent applications worldwide including three pending provisional U.S.

patent applications, one Hong Kong application, and nine total pending non-U.S.

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Our intellectual property portfolio is continually evolving during prosecution of our applications.

We own or license multiple families of patent applications that are directed to our TOBI platform technology and our single-chain and multi-chain chimeric polypeptides and methods of use of these polypeptides alone and in combination.

We own or license multiple families of patent applications that are directed to our TOBI TM platform technology and our single-chain and multi-chain chimeric polypeptides and methods of use of these polypeptides alone and in combination.

Single-Chain Chimeric Polypeptides Licensed Patent Family

This family includes licensed patents and patent applications with claims directed to compositions of various single-chain chimeric polypeptides created using the TOBI platform.

This family includes licensed patents and patent applications with claims directed to compositions of various single-chain chimeric polypeptides created using the TOBI TM platform.

These licensed applications also include methods of use and manufacture thereof and methods of promoting the activation and proliferation of NK cells or T cells using our single-chain chimeric polypeptides.

As of December 31, 2025, this family, which includes HCW9302, includes U.S.

11,401,324, 11,987,619, and 12,018,071, one pending U.S.

utility patent application, one issued Japanese patent, and 13 pending patent applications filed in Europe, Australia, Canada, Israel, New Zealand, Japan, South Korea, China, Singapore, Hong Kong and Taiwan.

11,401,324, 11,987,619, and 12,018,071, two pending U.S.

utility patent applications, one issued Australian patent, one issued Chinese patent, one issued Israeli patent, two issued Japanese patents, one issued New Zealand patent, and 10 pending patent applications filed in Europe, Australia, Canada, Israel, Japan, South Korea, China, Singapore, Hong Kong and Taiwan.

The earliest predicted expiration date of any patent issuing from a patent application in this family is 2039.

Multi-Chain Chimeric Polypeptides Licensed Patent Family

This family includes licensed patents and patent applications with claims directed to compositions of various multi-chain chimeric polypeptides created using the TOBI platform.

This family includes licensed patents and patent applications with claims directed to compositions of various multi-chain chimeric polypeptides created using the TOBI TM platform.

These licensed applications also include methods of use and manufacture thereof and methods of promoting the activation and proliferation of NK cells or T cells using our multi-chain chimeric polypeptides.

As of December 31, 2025, this family, which includes claims encompassing HCW9218, HCW9201, HCW9206, HCW9228, HCW9207, and HCW9212, includes U.S.

11,518,792 and 11,884,712, six pending U.S.

utility patent applications, one issued Japanese patent, one issued Australian patent, one issued Singaporean patent, one issued Taiwanese patent, and 12 pending patent applications filed in Europe, Australia, Canada, Israel, Japan, New Zealand, South Korea, China, Singapore, Hong Kong and Taiwan.

11,518,792, 11,884,712, 12,269,654, 12,398,186, and 12,509,494, three pending U.S.

utility patent applications, one issued Japanese patent, one issued Australian patent, one issued European patent, one issued Israel patent, one issued New Zealand patent, one issued Singaporean patent, and eleven pending patent applications filed in Europe, Australia, Canada, Japan, South Korea, China, Singapore, Hong Kong, and Taiwan.

The earliest predicted expiration date of any patent issuing from a patent application in this family is 2039.

With respect to HCW9218, as of December 31, 2024, the composition is claimed in U.S.

11,518,792, four patents issued in Australia, Singapore, Japan and Taiwan, and eight pending patent applications filed in Europe, Canada, Israel, Japan, New Zealand, South Korea, China, and Hong Kong.

With respect to HCW9201, December 31, 2024, the composition is claimed in one allowed U.S.

utility patent application, one issued Singaporean patent, one issued Japanese patent and ten pending patent applications filed in Europe, Canada, Israel, Japan, New Zealand, South Korea, China, Singapore, Hong Kong and Taiwan.

With respect to HCW9218, as of December 31, 2025, the composition is broadly or narrowly claimed in U.S.

11,518,792, four patents issued in Australia, Europe, Israel, New Zealand, Singapore, and Japan, and six pending patent applications filed in Canada, Japan, South Korea, China, Taiwan, and Hong Kong.

With respect to HCW9201, December 31, 2025, the composition is broadly or narrowly claimed in U.S.

12,269,654, one issued European patent, one issued Israeli patent, one issued Singaporean patent, one issued Japanese patent, one issued New Zealand patent, and seven pending patent applications filed in Europe, Canada, Japan, China, Singapore, Hong Kong and Taiwan.

Wugen has obtained an exclusive license to these patent applications limited to use of the licensed chimeric polypeptides in manufacturing certain cellular therapy products.

With respect to HCW9206, December 31, 2024, the composition is claimed in U.S.

11,884,712 , one issued Singaporean patent, one issued Japanese patent and 11 pending patent applications filed in Europe, Australia, Canada, Israel, Japan, New Zealand, South Korea, China, Singapore, Hong Kong and Taiwan.

With respect to HCW9206, December 31, 2025, the composition is broadly or narrowly claimed in U.S.

11,884,712 , one issued Singaporean patent, one issued Japanese patent, one issued European patent, one Israeli patent, one New Zealand patent, and eight pending patent applications filed in Europe, Australia, Canada, Japan, China, Singapore, Hong Kong and Taiwan.

Wugen has obtained an exclusive license to these patent applications limited to use of the licensed polypeptides in manufacturing certain cellular therapy products.

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11,730,762, U.S.

11,738,052, two pending U.S.

utility patent applications, one issued Australian patent, one issued Japanese patent, and 16 pending patent applications filed in Europe, Australia, Canada, Israel, Japan, South Korea, Singapore, Hong Kong and China.

11,738,052, U.S.

12,479,899, one pending U.S.

utility patent application, one issued Australian patent, two issued Chinese patents, one issued European patent, two issued Japanese patents, and 14 pending patent applications filed in Europe, Australia, Canada, Israel, Japan, South Korea, Singapore, Hong Kong and China.

The earliest predicted expiration date of any patent issuing from a patent application in the first of these two families is 2039.

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Treating Age Related Disorders

These four families include licensed patent and patent applications with claims directed to methods of killing or reducing the number of senescent cells in a subject using our single-chain or multi-chain chimeric polypeptides.

As of December 2024, these four families, which include methods of using HCW9218, HCW9228 and HCW9302, include U.S.

11,672,826, 12,024,545, and 12,115,191, four pending U.S.

utility patent applications, one issued Japanese patent, and 33 pending patent applications filed in Europe, Australia, Canada, Israel, Japan, Hong Kong, South Korea, New Zealand, Singapore, and China.

These three families include licensed patent and patent applications with claims directed to methods of killing or reducing the number of senescent cells in a subject using our single-chain or multi-chain chimeric polypeptides.

As of December 2025, these three families, which include methods of using HCW9218, HCW9228 and HCW9302, include U.S.

11,672,826, 12,024,545, and 12,115,191, three pending U.S.

utility patent applications, one issued Chinese patent, two issued Japanese patents, and 22 pending patent applications filed in Europe, Australia, Canada, Israel, Japan, Hong Kong, South Korea, New Zealand, Singapore, and China.

The earliest predicted expiration date of any patent issuing from a patent application in the first of these three families is 2039.

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The earliest predicted expiration date of any patent issuing from a patent application in the third of these families is 2040.

The earliest predicted expiration date of any patent issuing from a patent application in the fourth of these families is 2042.

Methods of Activating Regulatory T Cells

This family includes patent applications with claims directed to methods of promoting the activation and proliferation of Regulatory T cells through the use of our single-chain or multi-chain chimeric polypeptides for ex vivo cell therapy use.

As of December 2024, this family, which includes methods of using HCW9213 and HCW9302, includes one pending U.S.

utility patent application and 10 pending patent applications filed in Australia, New Zealand, Singapore, Israel, Europe, Canada, Japan, China, Hong Kong, and South Korea.

As of December 2025, this family, which includes methods of using HCW9213 and HCW9302, includes U.S.

12,398,189, and 10 pending patent applications filed in Australia, New Zealand, Singapore, Israel, Europe, Canada, Japan, China, Hong Kong, and South Korea.

The earliest predicted expiration date of any patent issuing from a patent application in this family of applications is 2041.

This family includes patent applications with claims directed to anti-CD26 scFv antibodies.

As of December 2024, this family, which includes composition claims for HCW9106, includes one pending U.S.

utility patent application and six pending patent applications filed in Australia, Canada, Europe, China, Hong Kong, and Japan.

As of December 2025, this family, which includes composition claims for HCW9106, includes U.S.

12,497,462, one issued Japanese patent, and five pending patent applications filed in Australia, Canada, Europe, China, and Hong Kong.

The earliest predicted expiration date of any patent issuing from a patent application in this family of applications is 2041.

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New Chimeric Polypeptide Platform

As of December 31, 2024, HCW Biologics has filed two provisional patent applications related to a new chimeric polypeptide platform.

As of December 31, 2025, HCW Biologics has filed three U.S.

provisional patent applications, two U.S.

utility patent applications, one Taiwan patent application, and three international patent applications related to a new chimeric polypeptide platform.

The new chimeric polypeptide platform will be useful in the generation of polypeptides with therapeutic potential (e.g., useful in the field of inflammaging).

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We have an International Registration for the mark HCW BIOLOGICS for pharmaceutical research and development services, among other related services, in Class 42 and four national trademark applications pending therefrom with two registrations issued in the European Union and Japan.

In the future, we intend to file applications for trademark registrations in connection with our Company, our product candidates, and other technologies in various jurisdictions, including the United States as the products are further developed.

In the future, we intend to file applications for trademark registrations in connection with our product candidates, and other technologies in various jurisdictions, including the United States as the products are further developed.

Trade Secret Protection

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Wugen Exclusive Worldwide License Agreement

In December 2020, we entered into an exclusive worldwide license agreement with Wugen, for rights to use certain HCWB fusion protein molecules to develop, manufacture, and commercialize their cellular therapy products.

The term of the agreement will expire on a product-by-product and country-by-country basis, upon the later of (i) the expiration of the last-to-expire valid patent claim or (ii) ten (10) years from the first commercial sale of such product.

As consideration for the Wugen License, HCWB received shares of Wugen’s common stock, which was equivalent to a 5.6% ownership interest in Wugen as of December 31, 2024.

We may receive additional payments in the future, based upon the occurrence of certain development milestones.

We will be eligible to receive additional payments for commercialization milestones as well as single-digit royalties for commercial sales once product sales commence.

We retained all other rights and use of the licensed molecules outside of Wugen’s right to use the molecules to develop, manufacture, and commercialize cellular therapy products.

Wugen’s rights are limited to use of the licensed molecules in cellular therapy products, which are pharmaceutical or biological products, processes or therapies that contain or comprise cells (including without limitation, CIML NK cells or T cells) that have been engineered, modified, or otherwise manipulated ex vivo , but excludes regulatory T cell-based cellular therapy products.

Our retained rights include use of the molecules for injectable therapy product, regulatory T cell-based cellular therapy products, and manufacturing rights to the licensed molecules.

We oversee manufacturing and supply of these licensed molecules to Wugen, utilizing our internally-developed manufacturing process, under supply agreements with Wugen that have industry-standard terms.

Wugen funds all future clinical development and commercialization activities for the cellular therapy treatments developed by Wugen using the licensed molecules.

WY Biotech Exclusive Worldwide License Agreement

On November 17, 2024, HCW Biologics entered into an exclusive, worldwide License, Research, and Co-Development Agreement (the “WY Biotech License Agreement”) with WY Biotech Co., Ltd.

(the “WY Biotech”) for one of the Company’s preclinical, proprietary molecules.

As reported in the Company’s Form 8-K filed with the SEC on March 19, 2025, on March 18, 2025, the Company and WY Biotech agreed to amend the WY Biotech License Agreement.

The Company has now completed extensive preclinical studies that further support our belief in the potential for HCW11-006 for both an in vivo and ex vivo therapy.

The Company considers WY Biotech License Agreement provisions for the Opt-In Right to take over the development of HCW11-006 for the Americas markets to be an important feature of the WY Biotech License.

We believe our right to recapture this market is a potentially high value opportunity.

Upon the completion of a Phase 1 clinical trial in any jurisdiction, the Company has an “Opt-In Right,” which gives the Company the option to assume all control and responsibility for the development, manufacture and commercialization of the molecule licensed to WY Biotech in the Opt-In Territory.

The “Opt-In Territory” is North America, South America, and Central America.

Upon the completion of the exercise of the Opt-In Right, the Company will be responsible for all costs associated with research and development, manufacturing, clinical development, regulatory approval, and commercialization for the licensed molecule in the Opt-In Territory.

WY Biotech will pay the Company milestone payments as the licensed molecule advances through clinical trials and the first marketing approval is granted for the first territory in which the WY Biotech retains exclusive rights.

Upon commercialization, the Company will receive double-digit royalties on a product-by-product basis in each jurisdiction in which the WY Biotech retains exclusive rights, subject to adjustment in the event the Company exercises the Opt-In Right.

In addition, the Company will share a substantial portion of the net proceeds from any future transactions entered into by the WY Biotech, involving an exclusive license for the licensed molecule, an assignment of the WY Biotech License Agreement or the sale of the WY Biotech’s business that would permit the buyer to assume exclusive rights under the WY Biotech License Agreement, excluding transactions in the Greater China market.

The Company and WY Biotech have expressed their intent to work cooperatively with respect to the licensed molecule in the development stage, with a global focus for clinical development and partnering.

The WY Biotech License Agreement contains various representations, warranties, affirmative and negative covenants, events of default and related remedies as well as other customary provisions.

In December 2020, we entered into an exclusive worldwide license agreement with Wugen, under which Wugen licensed limited rights to develop, manufacture, and commercialize cell-based therapy treatments for cancer based on two of our internally-developed, multi-cytokine fusion protein molecules, HCW9201 and HCW9206.

The license included patents and applications that protect the underlying technology and use of the molecule HCW9201 and HCW9206, conveying rights to develop cell-based therapies for cancer.

In respect of Wugen, we retain all other rights to HCW9206, including manufacturing rights.

As part of a confidential Settlement Agreement with ImmunityBio, Inc.

The suspension will run for a period of one year from the effective date of the suspension and will end on May 29, 2026.

For further information, see “Item 1.

Business – Business Development and Out-License Programs.”

Trimmune Exclusive Worldwide License Agreement

On November 17, 2025, the Company and Beijing Trimmune Biotech Co., Ltd.

The deal also includes an option to license the exclusive China rights to clinical development and commercialization for in vivo applications of HCW9302.

The parties agreed to build unified clinical programs, and to work together in the business development operations when the HCW11-006 co-development project generates key clinical data, to actively explore business development opportunities with multi-national corporations.

HCW also has a payment-free, milestone-free, and royalty-free option to recapture the development and commercialization rights of this molecule for the United States, Canada, Central America, and South America (Opt-in Territory) after the conclusion of the Phase 1 clinical trial.

Trimmune is financially responsible for all costs associated with research and development, manufacturing, clinical development, regulatory approval, and commercialization for the molecule.

For further information, see “Item 1.

Business – Business Development and Out-License Programs.”

Contract Research Agreements

We have certain contract research agreements with contractors that were entered during the two years ended December 31, 2024 for the (i) hybridoma development, (ii) cell line improvement for higher manufacturing productivity, and (iii) research to support pre-clinical studies.

We have certain contract research agreements with contractors that we entered during the two years ended December 31, 2025 for the (i) hybridoma development, (ii) cell line improvement for higher manufacturing productivity, and (iii) collaborative research to support pre-clinical studies.

In respect of the hybridoma development and cell line improvement agreements, we own all rights to the resulting intellectual property, including the antibodies, sequences, and data.

To date, we have received several sequences and hybridomas from the contractors.

To date, we have received several sequences from the contractors.

For certain contractors, we are obligated to pay one future milestone payment upon filing and acceptance of an IND for each respective human antibody or protein from cell line;

however, no additional future development or financial obligations are

due under these contract research agreements.

however, no additional future development or financial obligations are due under these contract research agreements.

For certain research collaborations agreements, the resulting research intellectual property may be jointly owned or ownership may be based upon inventorship.

In those circumstances, the Company has obtained the exclusive option to an exclusive license for the research intellectual property

In those circumstances, the Company has the option to obtain an exclusive license for the research intellectual property

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition, and a strong emphasis on internally-developed products.

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We compete in the segments of the pharmaceutical, biotechnology, and other related markets that develop cancer therapies.

There are many other companies that have commercialized or are developing cancer therapies, including large pharmaceutical and biotechnology companies, such as Amgen, AstraZeneca/MedImmune, Bristol Myers Squibb Company, Merck & Co., Novartis Pharmaceuticals, Pfizer, and Genentech, a member of The Roche Group.

There are many other companies that have commercialized or are developing cancer therapies, including large pharmaceutical and biotechnology companies, such as AbbVie, Amgen, AstraZeneca/MedImmune, Bristol Myers Squibb Company, Merck & Co., Novartis Pharmaceuticals, Pfizer, Sanofi and Genentech, a member of The Roche Group.

We face significant competition from pharmaceutical and biotechnology companies that target specific tumor-associated antigens using immune cells or other cytotoxic modalities.

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Aging-related diseases are becoming a major focus in biopharma, as researchers and companies work to develop treatments for conditions like Alzheimer's.

Biotech innovators like Altos Labs and Unity Biotechnology are at the forefront, exploring ways to target aging itself by removing senescent cells and modifying metabolic pathways.

Biotech innovators like Altos Labs, Calico Life Sciences, Rubedo Life Sciences and Unity Biotechnology are at the forefront, exploring ways to target aging itself by removing senescent cells and modifying metabolic pathways.

In oncology, there's growing interest in using senescence removal to improve the effectiveness of cancer treatments.

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Autoimmune diseases, including alopecia areata, atopic dermatitis, and neurodegenerative disorders, are gaining increasing attention in biopharma.

We are initiating clinical development in this area using HCW9302, which recently received IND clearance from FDA for a Phase 1 clinical study for alopecia areata.

We initiated a Phase 1clinical study in this area using HCW9302, for alopecia areata.

We are aware of several other companies developing programs that utilize IL-2 for the selective expansion of T reg cells, including Amgen, Coya Therapeutics, Nektar Therapeutics, Genentech, a member of The Roche Group, Merck & Co., Bristol Myers Squibb Company, and Celgene, a subsidiary of Bristol Myers Squibb Company.

We are also aware of other companies with research or preclinical-stage programs in this area, including Synthorx, Moderna, and Xencor.

We are also aware of other companies with PD-1 or CTLA-4 agonist programs for the treatment of autoimmune diseases and transplant, including Coya Therapeutics, AnaptysBio, Celgene, a subsidiary of Bristol Myers Squibb Company, and Eli Lilly & Company.

We are also aware of other companies with PD-1 or CTLA-4 agonist programs for the treatment of autoimmune diseases and transplants, including Coya Therapeutics, AnaptysBio, Celgene, a subsidiary of Bristol Myers Squibb Company, and Eli Lilly & Company.

Additionally, preclinical studies are underway to explore HCW9302’s potential in targeting neurodegenerative diseases.

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HCW9302 is suitable for both in vivo subcutaneous injection strategies and T reg cell therapy.

In addition to alopecia areata, future plans include testing this molecule in transplant models, expanding its potential therapeutic applications.

Numerous companies, including Kite Pharma, Novartis, Bluebird Bio, and Autolus Therapeutics, renowned for their CAR-T cell therapies in oncology, are expanding their research to explore the potential of CAR-T therapies in autoimmune diseases.

In addition to alopecia areata, future plans include testing this molecule in transplant models and atopic dermatitis, expanding its potential therapeutic applications.

Numerous companies, including Kite Pharma, Novartis, Bristol Myers Squibb Company, Bluebird Bio, and Autolus Therapeutics, renowned for their CAR-T cell therapies in oncology, are expanding their research to explore the potential of CAR-T therapies in autoimmune diseases.

For instance, Kite Pharma and Novartis are investigating CAR-T treatments for autoimmune conditions like multiple sclerosis (MS) and systemic lupus erythematosus.

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We have a novel approach to the treatment of senescence-associated diseases.

Bronchopulmonary dysplasia (“BPD”) presents unmet needs, particularly in addressing long-term lung damage and inflammation in premature infants.

BPD presents unmet needs, particularly in addressing long-term lung damage and inflammation in premature infants.

With growing pharma competition, treatments targeting senescent cell removal from the lungs are emerging as a promising approach to improve lung function and reduce BPD-related complications.

Our recent research suggests that immunotherapeutic agent contain TGF- b Trap and IL-15 could be potential therapy for human BPD specifically targeting the mechanism that impairs lung development.

Our multispecific T‑cell engager program, the Company’s BIG‑BiTE, consists of bi‑specific and tri‑specific T‑cell engagers designed to recruit and activate endogenous T cells against tumor antigens, enhancing potency and selectivity compared to conventional bispecific formats.

The oncology T‑cell engager landscape is highly competitive, with established and emerging programs from biotech and pharmaceutical companies, including AbbVie, BMS, Sanofi, Lilly, Amgen’s bispecifics, Genmab/Daiichi Sankyo’s multispecific platforms, and numerous CD3‑engager programs in development targeting both hematologic and solid tumors.

Unlike some competitors whose constructs are limited to dual targeting or may exhibit on‑target/off‑tumor toxicities, HCW BIG‑Bites’ multispecific architecture is engineered for optimized synapse formation, improved tumor specificity, and reduced cytokine‑release risk.

We believe this differentiated design may enable broader tumor coverage, deeper responses, and an improved safety profile.

The market opportunity for effective T‑cell engagers is substantial, with expanding indications and significant unmet needs in both hematologic malignancies and solid tumors.

Our clinical goals are to validate safety and robust anti‑tumor activity in early‑phase studies, advance select candidates toward development, and position HCW BIG‑Bites for potential commercial success.

Several immune checkpoint inhibitors have been approved for the treatment of a limited number of cancer indications.

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and its product, Keytruda®.

Recently, several pharmaceutical companies have been licensing various versions of PD-1 from Greater China and other small biotech firms, further reflecting the growing interest in innovative immune-modulating therapies.

Recently, several pharmaceutical companies have been licensing various versions of PD-1 from China and other small biotech firms like Summit Therapeutics, Akeso Biopharma, further reflecting the growing interest in innovative immune-modulating therapies.

It may also incentivize innovation and the development of new formulations, combinations, or delivery methods to maintain market share and competitive advantage.

It may also incentivize innovation and the development of new formulations, combinations, or

delivery methods to maintain market share and competitive advantage.

The following list summarizes key immune checkpoint inhibitors along the companies that own these drugs and their patent expiration dates:

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The processes for obtaining regulatory approvals in the United States and in foreign countries and jurisdictions, along with subsequent compliance with applicable statutes and regulations and other regulatory authorities, require the expenditure of substantial time and financial resources.

FDA Approval Process

FDA Review and Approval Process

In the United States, biological products are subject to extensive regulation by the FDA.

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Biological products used for the prevention, treatment, or cure of a disease or condition of a human being are subject to regulation under the FDC Act, with the exception that the section of the FDC Act which governs the approval of drugs via New Drug Applications (“NDAs”), does not apply to the approval of biologics.

In contrast, biologics are approved for marketing under provisions of the Public Health Service Act (“PHSA”), via a Biologics License Application (“BLA”).

In contrast, biologics are approved for marketing under provisions of the Public Health Service Act (“PHSA”) via Biologics License Applications (“BLAs”).

However, the application process and requirements for approval of BLAs are very similar to those for NDAs.

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Each protocol involving testing on U.S.

patients and subsequent protocol amendments must be submitted to the FDA as part of the IND.

The FDA may order the temporary or permanent discontinuation of a clinical trial at any time, or impose other sanctions, if it believes that the clinical trial either is not being conducted in accordance with FDA regulations or presents an unacceptable risk to the clinical trial patients.

participants and subsequent protocol amendments must be submitted to the FDA as part of the IND.

Imposition of a clinical hold may be full or partial.

The study protocol and informed consent information for patients in clinical trials must also be submitted to an institutional review board (“IRB”), for approval.

The study protocol and informed consent information for participants in clinical trials must also be submitted to an institutional review board (“IRB”), for approval before each trial begins.

The IRB will also monitor the clinical trial until completed.

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This group provides authorization for whether a trial may move forward at designated checkpoints based on access to certain data from the trial.

Investigator-initiated trials may proceed under an IND held by a clinical investigator or academic sponsor rather than the Company.

In such cases, the investigator is responsible for compliance with FDA requirements relating to informed consent, safety reporting, recordkeeping, and trial oversight.

Clinical trials to support BLAs for marketing approval are typically conducted in three sequential phases.

In Phase 1, the initial introduction of the drug or biologic into patients, the product is tested to assess safety, dosage tolerance, metabolism, pharmacokinetics, pharmacological actions, side effects associated with drug or biologic exposure, and to obtain early evidence of a treatment effect if possible.

Phase 2 usually involves trials in a limited patient population to determine the effectiveness of the biologic for a particular indication, determine optimal dose and regimen, and to identify common adverse effects and safety risks.

If a compound demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain additional information about clinical effects and confirm efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites, to permit the FDA to evaluate the overall benefit-risk relationship of the biologic and to provide adequate information for the labeling of the product.

In most cases, the FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate the safety and efficacy of the biologic.

In rare instances, a single Phase 3 trial may be sufficient when either (1) the trial is a large, multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically impossible or (2) the single trial is supported by confirmatory evidence.

Approval on the basis of a single trial may be subject to a requirement for additional post-approval studies.

In Phase 1, the initial introduction of the investigational drug or biologic into research participants, the product is tested to assess safety, dosage tolerance, metabolism, pharmacokinetics, pharmacological actions, side effects associated with drug or biologic exposure, and to obtain early evidence of a treatment effect if possible.

A sponsor who wishes to conduct a clinical trial outside of the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND.

If a foreign clinical trial is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of a BLA.

The FDA will accept a well-designed and well-conducted foreign clinical trial not conducted under an IND if the clinical trial was conducted in accordance with GCPs and the FDA is able to validate the data through an onsite inspection if deemed necessary.

Phase 2 usually involves trials in a limited population to determine the effectiveness of the investigational biologic for a particular indication, determine optimal dose and regimen, and to identify common adverse effects and safety risks.

If a compound demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain additional information about clinical effects and confirm efficacy and safety in a larger number of participants, typically at geographically dispersed clinical trial sites, to permit the FDA to evaluate the overall benefit-risk relationship of the investigational biologic and to provide adequate information for the labeling of the product.

In many cases, particularly for prevalent diseases, the FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate the safety and efficacy of the biologic.

In many other conditions, a single Phase 3 trial may be sufficient when in conjunction with confirmatory evidence.

A single Phase 3 trial may also be sufficient, though it is less common, when the trial is a large, multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality, irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be practically or ethically impossible Approval on the basis of a single trial may be subject to a requirement for additional post-approval studies.

These phases may overlap or be combined.

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In addition, the manufacturer of an investigational biologic in a Phase 2 or Phase 3 clinical trial for a serious or life-threatening disease is required to make available, such as by posting on its website, its policy on evaluating and responding to requests for expanding access to such investigational drug or biologic.

After completion of the required clinical testing, a BLA is prepared and submitted to the FDA.

Concurrent with clinical trials, companies usually complete additional nonclinical studies and also must develop additional information about the chemistry and physical characteristics of the investigational biologic as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing quality batches of the product and, among other things, companies must develop methods for testing the identity, strength, quality, potency, and purity of the final product.

Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the investigational medicines do not undergo unacceptable deterioration over their shelf life.

After successful completion of the required clinical testing, a BLA is prepared and submitted to the FDA.

FDA approval of the BLA is required before marketing and distribution of the product may begin in the United States.

The BLA must include the results of all preclinical, clinical, and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture, and controls.

The BLA must include the results of all nonclinical, clinical, and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture, and controls.

The cost of preparing and submitting a BLA is substantial.

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applications classified as Priority Review are reviewed within six months of the date the FDA files the BLA.

A BLA can be classified for Priority Review when the FDA determines the biologic has the potential to treat a serious or life-threatening condition and, if approved, would be a significant improvement in safety or effectiveness compared to available therapies.

The review process for both standard and priority reviews may be extended by the FDA for three or more additional months to consider certain late-submitted information, or information intended to clarify information already provided in the BLA submission.

A BLA can be classified for Priority Review when the FDA determines the investigational biologic has the potential to treat a serious or life-threatening condition and, if approved, would be a significant improvement in safety or effectiveness compared to available therapies.

The review process for both standard and priority reviews may be extended by the FDA for three months to consider information that the FDA deems to be a major amendment to the BLA.

The FDA may also refer applications for novel biologic products, as well as biologic products that present difficult questions of safety or efficacy, to be reviewed by an advisory committee—typically a panel that includes clinicians, statisticians and other experts—for review, evaluation, and a recommendation as to whether the BLA should be approved.

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Additionally, the FDA will inspect the facility or the facilities at which the biologic product is manufactured.

The FDA will not approve the product unless compliance with cGMP is satisfactory and the BLA contains data that provide substantial evidence that the drug is safe and effective, or the biologic is safe, pure, potent, and effective, in the respective claimed indication.

The FDA will not approve the product unless compliance with cGMP is satisfactory and the BLA contains data that demonstrate that the biologic is safe, pure, potent, and effective, in the claimed indication.

After the FDA evaluates the BLA and completes any clinical and manufacturing site inspections, it issues either an approval letter or a complete response letter.

A complete response letter generally outlines the deficiencies in the BLA submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application for approval.

A complete response letter generally outlines the deficiencies the FDA identified during its review of the BLA and may require substantial additional testing, or information, in order for the FDA to reconsider the application for approval.

If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the BLA, the FDA will issue an approval letter.

The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included.

Even if such data and information are submitted, the FDA may decide that the BLA does not satisfy the criteria for approval.

An approval letter authorizes commercial marketing and distribution of the biologic with specific prescribing information for specific indications.

As a condition of BLA approval, the FDA may require a risk evaluation and mitigation strategy (“REMS”), to help ensure

that the benefits of the biologic outweigh the potential risks to patients.

As a condition of BLA approval, the FDA may require a risk evaluation and mitigation strategy (“REMS”), to help ensure that the benefits of the biologic outweigh the potential risks to patients.

A REMS can include medication guides, communication plans for healthcare professionals, and elements to assure a product’s safe use (“ETASU”).

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The requirement for a REMS can materially affect the potential market and profitability of the product.

Moreover, the FDA may require substantial post-approval testing and surveillance to monitor the product’s safety or efficacy.

Moreover, the FDA may require substantial post-approval testing and surveillance to monitor the product’s safety or efficacy and may limit further marketing of the product based on the results of this post-approval testing or surveillance.

Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing.

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Fast Track Designation and Priority Review

The FDA is required to facilitate the development, and expedite the review, of drugs or biologic products that are intended for the treatment of a serious or life-threatening disease or condition for which there is no effective treatment and which demonstrate the potential to address unmet medical needs for the condition.

Fast track designation may be granted for a product that is intended to treat a serious or life-threatening disease or condition for which there is no effective treatment and preclinical or clinical data demonstrate the potential to address unmet medical needs for the condition.

The FDA has a number of programs intended to expedite the development or review of a marketing application for an investigational biologic.

For example, an investigational biologic is eligible for fast track designation if it is intended to treat a serious or life-threatening disease or condition for which there is no effective treatment and demonstrates the potential to address unmet medical needs for the disease or condition.

Fast track designation applies to both the product and the specific indication for which it is being studied.

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FDA must determine if the product candidate qualifies for fast track designation within 60 days of receipt of the sponsor’s request.

For fast-track products, sponsors may have more frequent interactions with the FDA and the FDA may initiate review of sections of a fast-track product’s BLA before the application is complete.

For fast-track products, sponsors may have more frequent interactions with the applicable FDA review team during product development.

With regard to a fast track investigational biologic, the FDA may initiate review of sections of a fast-track product’s BLA on a rolling basis before the application is complete.

This “rolling review” is available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a fast-track product may be effective.

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The FDA will attempt to direct additional resources to the evaluation of an application designated for priority review in an effort to facilitate the review.

The FDA endeavors to review applications with priority review designations within six months of the filing date as compared to ten months for review of original BLAs under its current review goals.

Breakthrough Therapy Designation

The FDA is also required to expedite the development and review of applications for approval of biologics that are intended to treat a serious or life-threatening disease or condition where preliminary clinical evidence indicates that the biologic may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

The FDA is also required to expedite the development and review of applications for approval of biologics that are intended to treat a serious or life-threatening disease or condition where preliminary clinical evidence indicates that the investigational biologic, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

Under the breakthrough therapy program, the sponsor of a new product candidate may request that the FDA designate the product candidate for a specific indication as a breakthrough therapy concurrent with, or after, the filing of the IND for the product candidate.

The FDA must determine if the product candidate qualifies for breakthrough therapy designation within 60 days of receipt of the sponsor’s request.

The FDA may take certain actions with respect to breakthrough therapies, including holding meetings with the sponsor throughout the development process, providing timely advice to the product sponsor regarding development and approval, involving more senior staff in the review process, assigning a cross-disciplinary project lead for the review team and taking other steps to design the clinical studies in an efficient manner.

This designation includes all of the fast track program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the investigational biologic, including involving more senior staff in the review process, assigning a cross-disciplinary project lead for the review team, and taking other steps to design the clinical studies in an efficient manner.

Accelerated Approval

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All promotional materials for product candidates approved under accelerated regulations are subject to prior review by the FDA.

The Food and Drug Omnibus Reform Act (“FDORA”) was enacted, which includes provisions related to the accelerated approval pathway.

Pursuant to FDORA, the FDA is authorized to require a post-approval study to be underway prior to approval or within a specified time period following approval.

FDORA also requires the FDA to specify conditions of any required post-approval study, which may include milestones such as a target date of study completion and requires sponsors to submit progress reports for required post-approval studies and any conditions required by the FDA not later than 180 days following approval and not less frequently than every 180 days thereafter until completion or termination of the study.

FDORA enables the FDA to initiate enforcement action for the failure to conduct with due diligence a required post-approval study, including a failure to meet any required conditions specified by the FDA or to submit timely reports.

The FDA is authorized to require a post-approval study to be underway prior to approval or within a specified time period following approval.

The FDA must also specify conditions of any required post-approval study, which may include milestones such as a target date of study completion.

Sponsors must submit progress reports for required post-approval studies and any conditions required by the FDA not later than 180 days following approval and not less frequently than every 180 days thereafter until completion or termination of the study.

The FDA can initiate an enforcement action for the failure to conduct with due diligence a required post-approval study, including a failure to meet any required conditions specified by the FDA or to submit timely reports.

Regenerative Medicine Advanced Therapy Designation

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Pediatric Information

Under the Pediatric Research Equity Act (“PREA”), BLAs or supplements to BLAs must contain data to assess the safety and effectiveness of the biological product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the biological product is safe and effective.

Under the Pediatric Research Equity Act (“PREA”), BLAs or supplements to BLAs must contain data to assess the safety and effectiveness of the biological product candidate for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the biological product is safe and effective.

The FDA may grant full or partial waivers, or deferrals, for submission of data.

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Adverse event reporting and submission of periodic reports are required following the FDA approval of a BLA.

The FDA also may require post-marketing testing, known as Phase 4 testing, REMS, and surveillance to monitor the effects of an approved product, or the FDA may place conditions on an approval that could restrict the distribution or use of the product.

The FDA also may require post-marketing testing, REMS, and surveillance to monitor the effects of an approved product, or the FDA may place conditions on an approval that could restrict the distribution or use of the product.

In addition, quality control, biological product manufacture, packaging, and labeling procedures must continue to conform to cGMP after approval.

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Regulatory authorities may withdraw product approvals or request product recalls if a company fails to comply with regulatory standards, if it encounters problems following initial marketing, or if previously unrecognized problems are subsequently discovered.

The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) creates an abbreviated approval pathway for biological products shown to be highly similar to or interchangeable with an FDA-licensed reference biological product.

The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) created an abbreviated approval pathway for biological products shown to be highly similar to or interchangeable with an FDA-licensed reference biological product.

Biosimilars are licensed based on the FDA’s findings of safety, purity and potency for a previously-FDA-licensed product called a reference product.

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The first biosimilar was approved in 2015, and the first interchangeable product was approved in 2021.

Complexities associated with the larger, and often more complex, structures of

biological products, as well as the process by which such products are manufactured, pose significant hurdles to biosimilar product implementation, which are still being evaluated by the FDA.

Complexities associated with the larger, and often more complex, structures of biological products, as well as the process by which such products are manufactured, pose significant hurdles to biosimilar product implementation, which are still being evaluated by the FDA.

A reference product is granted 12 years of exclusivity from the time of first licensure, or BLA approval, of the reference product, and during that 12 years of data exclusivity, no application for a biosimilar relying on the reference product can be submitted for four years.

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Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or criminal penalties and private litigation.

For example, the California Consumer Privacy Act (“CCPA”), which went into effect on January 1, 2020, creates new data privacy obligations for covered companies and provides new privacy rights to California residents.

On January 1, 2023, the California Privacy Rights Act (“CPRA”), which substantially amends the CCPA, went into effect.

For example, the California Consumer Privacy Act (“CCPA”), which went into effect on January 1, 2020, imposes data privacy obligations for covered companies, including, but not limited to, providing specific disclosures in privacy notices and affording California residents certain rights related to their personal data.

On January 1, 2023, the California Privacy Rights Act (“CPRA”), which imposes additional obligations on covered companies and substantially modifies the CCPA, went into effect.

The CCPA and CPRA provide for unlimited civil penalties for violations, as well as a private right of action for data breaches that is expected to increase data breach litigation.

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Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization.

In addition, companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products.

In addition, companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement

for their companion pharmaceutical or biological products.

Similar challenges to obtaining coverage and reimbursement, applicable to pharmaceutical or biological products, will apply to companion diagnostics.

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government rebate programs and additional downward pressure on pharmaceutical product prices.

Several healthcare reform proposals recently culminated in the enactment of the Inflation Reduction Act (“IRA”) in August 2022, which, among other things, allows HHS to directly negotiate the selling price of a statutorily specified number of drugs and biologics each year that CMS reimburses under Medicare Part B and Part D.

Several healthcare reform proposals culminated in the enactment of the Inflation Reduction Act (“IRA”) in August 2022, which, among other things, requires HHS to directly negotiate the selling price of a statutorily specified number of drugs and biologics each year that CMS reimburses under Medicare Part B and Part D.

The negotiated price may not exceed a statutory ceiling price.

Only high-expenditure single-source biologics that have been approved for at least 11 years (7 years for drugs) can be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year.

Only high-expenditure single-source biologics that have been approved for at least 11 years (7 years for single-source drugs) are eligible to be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year.

For 2026, the first year in which negotiated prices become effective, CMS selected 10 high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been announced.

CMS has selected 15 additional Medicare Part D drugs for negotiated maximum fair pricing in 2027.

For 2028, an additional 15 drugs, which may be covered under either Medicare Part B or Part D, will be selected, and for 2029 and subsequent years, 20 Part B or Part D drugs will be selected.

A drug or biological product that has an orphan drug designation for only one rare disease or condition will be excluded from the IRA’s price negotiation requirements, but will lose that exclusion if it receives designations for more than one rare disease or condition, or if is approved for an indication that is not within that single designated rare disease or condition, unless such additional designation or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for selection for negotiation.

In addition, CMS has selected and announced the negotiated maximum fair price for 15 additional Medicare Part D drugs, which will become effective in 2027.

For 2028, CMS has selected an additional 15 drugs, comprised of drugs covered under Medicare Part D and, for the first time, drugs payable under Medicare Part B.

For 2029 and subsequent years, 20 Part B or Part D drugs will be selected.

Currently, a drug or biological product that has an orphan drug designation for only one rare disease or condition will be excluded from the IRA’s price negotiation requirements, but will lose that exclusion if it receives designations for more than one rare disease or condition, or if is approved for an indication that is not within that single designated rare disease or condition, unless such additional designation or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for selection for negotiation.

However, as a result of a statutory amendment enacted in July 2025, beginning with the 2028 negotiated price applicability year, a drug may be designated for more than one rare disease or condition and still be excluded from price negotiation, as long as the only approved indications are for such rare diseases or conditions.

The IRA also imposes rebates on Medicare Part B and Part D drugs whose prices have increased at a rate greater than the rate of inflation, and in November 2024, CMS finalized regulations for these inflation rebates.

The IRA also extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

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Thus, while it is unclear how the IRA will be implemented, it will likely have a significant impact on the biopharmaceutical industry and the pricing of prescription drug products.

The Trump Administration is pursuing policies to reduce regulations and expenditures across government including at HHS, which include the FDA and CMS, and related agencies.

For example, on May 12, 2025, President Trump issued an Executive Order that, among other things, required HHS, within 30 days, to establish and communicate to drug manufacturers most favored nation (“MFN”) price targets designed to bring drug prices for American patients in line with those in comparably developed nations.

If significant progress towards MFN pricing is not achieved, the Executive Order requires HHS to propose a rulemaking to implement MFN pricing.

Recently, on December 23, 2025, CMS issued proposed regulations to establish, under the Center for Medicare and Medicaid Innovation, two mandatory MFN demonstration models under Medicare Parts B and D, respectively.

If these rules or other MFN pricing rules are finalized, they are likely to reduce prices of at least some drugs in the United States, if they are also sold in comparator countries.

Even if a company does not market its drugs in such countries, the company could be indirectly affected if its drugs compete with drugs whose prices were reduced as a result of MFN pricing initiatives.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access, and marketing cost disclosure and transparency measures, and in some cases, designed to encourage importation from other countries and bulk purchasing.

In addition, the FDA issued a final rule in 2020 providing guidance for states to build and submit importation proposals for drugs from Canada, and the FDA authorized the first such plan in Florida in 2024, but implementation of Florida’s plan has been extended until May 6, 2026.

It is unclear how this program will be implemented, including which drugs will be chosen, and

whether it will be subject to legal challenges in the United States or Canada.

Other states have also submitted proposals that are pending review by the FDA

We expect that additional state and federal healthcare reform measures could be adopted in the future.

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The CHMP and CAT are also responsible for providing guidelines on ATMPs.

These guidelines provide additional guidance on the factors that the EMA will consider in relation to the development and evaluation of ATMPs and include, among other things, the preclinical

studies required to characterize ATMPs;

These guidelines provide additional guidance on the factors that the EMA will consider in relation to the development and evaluation of ATMPs and include, among other things, the preclinical studies required to characterize ATMPs;

the manufacturing and control information that should be submitted in a marketing authorization application;

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For example, New Chemical Entities (“NCE”), approved in the European Union generally qualify for eight years of data exclusivity and ten years of market exclusivity.

Data exclusivity is the period during which another applicant cannot rely on the MA holder’s pharmacological, toxicological, and clinical data in support of another MA for the purposes of submitting an application, obtaining marketing authorization or placing the product on the market.

authorization or placing the product on the market.

But after eight years, a generic or biosimilar product application may be submitted and generic companies may rely on the MA holder’s data.

6 unchanged sentences

This oversight applies both before and after grant of manufacturing licenses and marketing authorizations.

It includes control of

compliance with EU good manufacturing practices rules, manufacturing authorizations, pharmacovigilance rules, and requirements governing advertising, promotion, sale, and distribution, recordkeeping, importing, and exporting of medicinal products.

It includes control of compliance with EU good manufacturing practices rules, manufacturing authorizations, pharmacovigilance rules, and requirements governing advertising, promotion, sale, and distribution, recordkeeping, importing, and exporting of medicinal products.

Failure by us or by any of our third-party partners, including suppliers, manufacturers, and distributors to comply with EU laws and the related national laws of individual EU Member States governing the conduct of clinical trials, manufacturing approval, marketing authorization of medicinal products, and marketing of such products, both before and after grant of marketing authorization, statutory health insurance, bribery and anti-corruption, or other applicable regulatory requirements may result in administrative, civil, or criminal penalties.

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Human Capital Management

Our approach to human capital resource management starts with our mission to discover and develop novel immunotherapies to lengthen health span by disrupting the link between chronic, low-grade inflammation and age-related diseases.

Our approach to human capital resource management starts with our mission to discover and develop novel immunotherapies to lengthen health span and improve quality of life for people suffering from diseases promoted by low-grade chronic inflammation.

Our industry exists in a complex regulatory environment.

23 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business