What changed in this filing

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Item 1. Business

2026-02-23 compared with 2025-03-03 · 822 added, 723 removed, 734 unchanged (68% of the section changed)

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Forward-looking statements include, but are not limited to:

• our ability to successfully commercialize ANKTIVA;

• our ability to obtain incremental approvals for ANKTIVA for new indications from the FDA or clearances or approvals from international regulatory agencies for the treatment of patients with NMIBC or other indications;

• potential future uses and applications of ANKTIVA, including as a lymphopenia rescue agent, and use in cancer vaccines and across multiple tumor types;

• our ability to successfully commercialize ANKTIVA globally in NMIBC, NSCLC or other indications or any future approved products in the U.S.

or internationally;

• our ability to obtain incremental approvals for ANKTIVA for new indications, including, without limitation, in BCG-unresponsive NMIBC with papillary tumors and NSCLC from the FDA or clearances or approvals from international regulatory agencies for the treatment of patients with NMIBC, NSCLC or other indications;

• potential future uses and applications of ANKTIVA, including as a lymphopenia rescue agent in solid tumors or other indications, and use in cancer vaccines and across multiple tumor types;

• our ability to develop next-generation therapies and vaccines that complement, harness, and amplify the immune system to defeat cancers and infectious diseases;

• our ability to obtain additional financing to fund our operations and complete the commercialization of our approved product and the development and commercialization of our other product candidates;

• our ability to meet our payment obligations under the RIPA and to service the interest on our related-party promissory note and repay such note, to the extent required;

• our ability to comply with the terms, conditions, covenants, restrictions, and obligations set forth in the RIPA and related transaction documents;

• our expectations regarding the potential benefits of our strategy and technology;

• our ability to forecast operating results and make period-to-period comparisons predictive of future performance due to fluctuations in warrant and derivative values;

• our expectations regarding the operation and effectiveness of our product candidates and related benefits;

• our ability to utilize multiple modes to induce cell death;

• our ability to obtain additional financing to fund our operations and advance the commercialization of our approved product and the development and commercialization of our other product candidates;

• our ability to comply with the terms, conditions, covenants, restrictions, and obligations set forth in the RIPA and related transaction documents, including payment obligations and servicing the interest on our related-party promissory note and the repayment of such note, to the extent required;

• our expectations regarding the potential benefits of our Cancer BioShield platform (comprises multiple therapeutic modalities to activate immune response) and our strategy and technology;

• our ability to forecast operating results and make period-to-period comparisons predictive of future performance due to fluctuations in warrant, derivative, and fair value accounting measurement values;

• our expectations regarding the operation and effectiveness of our approved product and product candidates and related benefits;

• our ability to utilize multiple modes to induce cell death in cancers and infectious disease;

• our beliefs regarding the benefits and perceived limitations of competing approaches, and the future of competing technologies and our industry;

• details regarding our strategic vision and planned product candidate pipeline;

• our beliefs regarding the success, cost and timing of our product candidate development activities and current and future clinical trials and studies, including study design and the enrollment of patients;

• the timing of the development and commercialization of our other product candidates;

• our expectations regarding our ability to utilize the Phase 1/2 aNK and haNK ® clinical trials data to support the development of our product candidates, including our taNK, t‑haNK ™ , MSC, and M-ceNK ™ product candidates;

• our expectations regarding the development, application, commercialization, marketing, prospects and use generally of our product candidates, including hAd5 constructs, and PD-L1 t‑haNK and M-ceNK;

• our beliefs regarding the success, cost and timing of our approved product and product candidate development activities and current and future clinical trials and studies, including study design and the enrollment of patients;

• whether the NCCN will add recommending ANKTIVA for BCG-unresponsive NMIBC with papillary tumors in addition to the existing recommendation for BCG-unresponsive NMIBC CIS with or without papillary tumors after our submission on the anticipated timeline or at all;

• our expectations regarding our ability to utilize the Phase 1/2 aNK, haNK ® , taNK, and NK-CAR (t-haNK ™ ) clinical trials data to support the development of our product candidates, including our NK-CAR (t‑haNK), MSC, and M-ceNK ™ product candidates;

• our expectations regarding the development, clinical trials timeline, application, commercialization, marketing, prospects and use generally of our product candidates, including hAd5 constructs, and PD-L1 t‑haNK and M-ceNK;

• the timing or likelihood of regulatory filings or other actions and related regulatory authority responses in the U.S.

and jurisdictions outside of the U.S., including any planned IND, BLA, NDA or MAA or similar filings or pursuit of accelerated regulatory approval pathways or orphan drug status and Breakthrough Therapy, Fast Track or RMAT designations and any designation’s eventual impact on BLA submission or approval timing and or approval probability;

and jurisdictions outside of the U.S., including any planned meetings, IND, BLA, NDA or MAA or similar filings or pursuit of accelerated regulatory approval pathways or orphan drug status and Breakthrough Therapy , Fast Track or RMAT designations and any designation’s impact on BLA submission filing or approval timing and or approval probability;

• our ability to successfully address the May 2025 RTF letter received from the FDA for the sBLA for the BCG-unresponsive NMIBC with papillary tumors indication and the recommendation from the FDA to submit additional information in support of filing for review of the sBLA, and whether or not there is a need for the initiation or design of a new RCT, which we could ultimately be required to complete;

• our ability to implement an integrated discovery ecosystem and the operation of that planned ecosystem, including being able to regularly add neoepitopes and subsequently formulate new product candidates;

• the ability and willingness of strategic collaborators to share our vision and effectively work with us to achieve our goals;

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• the ability and willingness of various third parties to engage in research and development activities involving our product candidates, and our ability to leverage those activities;

• the ability and willingness of various third parties to engage in research and development activities involving our product or product candidates, and our ability to leverage those activities;

• our ability to attract additional third-party collaborators;

• our expectations regarding the ease of administration associated with our product candidates;

• our expectations regarding patient compatibility associated with our product candidates;

• our beliefs regarding the potential markets for our product candidates and our ability to serve those markets;

• our ability to enter into clinical, regulatory and commercial arrangements internationally to accelerate the development and commercialization of ANKTIVA and our other product candidates;

• our expectations regarding the ease of administration associated with our approved product and product candidates;

• our expectations regarding patient compatibility associated with our approved product and product candidates;

• our beliefs regarding the potential markets for our approved product and product candidates and our ability to serve those markets;

• our expectations regarding the timing of enrollment and submission of our clinical trials, and protocols and timing of data read-outs related to such trials;

• our ability to produce a cytokine fusion protein, a DNA or recombinant protein vaccine, or a cell therapy;

• our beliefs regarding the potential manufacturing and distribution benefits associated with our product candidates, and our third-party CMOs’ abilities to follow cGMP standards to scale up the production of our product candidates;

• our plans regarding our manufacturing facilities and our belief that our manufacturing is capable of being conducted in‑house;

• our beliefs regarding the potential manufacturing and distribution benefits associated with our approved product and product candidates, and our third-party CMOs’ abilities to follow cGMP standards to scale up the production of our approved product and product candidates;

• our plans regarding manufacturing and distribution of our approved product and potential future products, including the enhancement of our in-house manufacturing capabilities;

• our belief in the potential of our cytokine fusion proteins, DNA or recombinant protein vaccines, or cell therapies, and the fact that our business is based upon the success individually and collectively of these platforms;

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• the ability to obtain and maintain regulatory approval of our approved product and to obtain and maintain regulatory approval of any of our other product candidates, and any related restrictions, limitations and/or warnings in the label of any approved product candidate;

• our ability to successfully commercialize ANKTIVA or any future approved products;

• the rate and degree of market acceptance of any approved products;

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• the accuracy of our estimates regarding our future revenue, as well as our future operating expenses, capital requirements and needs for additional financing;

• our ability to obtain, maintain, protect, and enforce patent protection and other proprietary rights for our approved product and our other product candidates and technologies;

• our ability to obtain, maintain, protect, and enforce patent protection and other proprietary rights for our approved product and our other product candidates, and other technologies in development;

• the terms and conditions of licenses granted to us and our ability to license additional intellectual property relating to our product, product candidates and technology;

• our expectations regarding the results of market access initiatives and coverage under medical reimbursement policies;

• our expectations regarding the abilities of our international partners to drive commercialization of ANKTIVA in the EU and MENA regions;

• shelf life of ANKTIVA drug substance and drug product and availability of product supply;

• our global expansion efforts;

• our global expansion efforts and the accuracy of our assumptions related to tariffs and government policy changes, including Most-Favored Nation Prescription Drug Pricing;

• any government shutdown or budget disruption, which could adversely affect the U.S.

and global economies, and materially and adversely affect our business and/or our future BLA submissions;

• the impact on us, if any, if the CVRs held by former Altor stockholders become due and payable in accordance with their terms;

• the impact on us, if any, if the CVRs held by former Altor stockholders become due and payable;

• regulatory developments in the U.S.

and foreign countries.

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Forward-looking statements include statements that are not historical facts and can be identified by terms such as “anticipates,” “believes,” “continues,” “goal,” “could,” “estimates,” “scheduled,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “indicate,” “projects,” “seeks,” “should,” “will,” “would,” “strategy,” and variations of such words or similar expressions.

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You should read this Annual Report completely and with the understanding that our actual future results may be materially different from what we expect.

ImmunityBio, ImmunityBio Care, ANKTIVA, ThAnktiva, haNK, taNK, ceNK, NK-92, Nant Cancer Vaccine, NANT 001, NANT XL, NANT 001 and Design, QUILT, Outsmart Your Disease, Smart Therapies for Difficult Diseases, NantKwest, VivaBioCell, and Infacell are trademarks or registered trademarks of ImmunityBio, Inc., its subsidiaries and affiliates.

ImmunityBio, ImmunityBio Care, ANKTIVA, ThAnktiva, haNK, taNK, ceNK, NK-92, Nant Cancer Vaccine, BioShield (and other BioShield-related trademarks), NANT 001, NANT XL, NANT 001 and Design, QUILT, Outsmart Your Disease, Smart Therapies for Difficult Diseases, NantKwest, VivaBioCell, and Infacell are trademarks or registered trademarks of ImmunityBio, Inc., its subsidiaries and affiliates.

ANKTIVA has been approved by the U.S.

FDA for use with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors.

FDA, the UK MHRA, and K.S.A.

SFDA and has been granted conditional marketing authorization from the EC (EMA) for the EU and Iceland, Liechtenstein, and Norway for use with BCG for the treatment of adult patients with BCG-unresponsive NMIBC CIS with or without papillary tumors.

It has also been conditionally approved by the SFDA in Saudi Arabia for use with CPIs in metastatic NSCLC.

Other than as set forth in such specific approved label, our product candidates, including N-803, are investigational agents that are restricted by federal law to investigational use only, and safety and efficacy have not been established by any agency, including the FDA.

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We do not intend our use or display of other companies’ products or trade names or trademarks to imply a relationship with, or endorsement or sponsorship of us, by any other companies.

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Founder’s Vision for Next-Generation Immunotherapy

A Message from Patrick Soon-Shiong, M.D., Founder of ImmunityBio, Inc.

Founder’s Vision

My 35-Year Quest to Change the Paradigm of Cancer Care by Activating the Body’s Immune System and Natural Killer Cells.

Founder’s Hypothesis

For the past 35 years, through my experience at UCLA treating both diabetic patients with pancreas transplants, and pancreatic cancer patients with pancreatic surgery (Whipple’s), I realized that the body had opposing immune systems:

on the one hand, cytotoxic systems to reject the transplanted pancreas and on the other hand immuno-evasion systems to allow pancreatic cancer to grow.

By 1990, I came to realize that the common denominator was the NK cell which on the one hand interacted with killer T cells to reject a transplanted organ and on the other hand, the killer NK and T cells were blocked by the tumor, allowing the tumor cells to grow.

At that time, I realized that the very therapy patients were receiving (high-dose chemotherapy and radiation) aided in the destruction of the very cells patients needed to cure cancer.

Of concern was the realization that the standards-of-care physicians were pursuing were based on the assumption that killing the tumor and achieving a short-term response would win the war against

In fact, a short-term battle would be won by observing a response rate, but the war lost because of the destruction of important cells called lymphocytes by our chemotherapy and radiation treatment, preventing the formation of memory T cells and long-term duration of response – duration matters, T cell memory matters.

Thus began the hypothesis that if we could harness the activity of lymphocytes – specifically NK and killer T cells, the potential existed to outsmart the immuno-evasion of cancer and unleash the body’s immune system to treat cancer with immunotherapy for long-term overall survival and indeed even prevent cancer in patients with high risk.

However, I faced the challenge of 50 years of standards of care which relied on high-dose chemotherapy and radiotherapy.

The notion that the standard-of-care would rapidly destroy these lymphocytes, the very cells needed to kill the tumor and establish T and NK cell memory, was difficult to convince the medical establishment and regulatory authorities.

The possibility that our standard-of-care was indeed responsible for preventing long-term complete remissions by the inadvertent process of destroying the very system engineered in our bodies to protect against cancer and infectious disease, was the quest that required challenging.

That is the mission of ImmunityBio and the recent recognition in 2025 by the FDA that ANKTIVA and PD-L1 t-haNK was granted a Regenerative Medicine Advanced Therapy (RMAT) designation for the reversal of lymphopenia in patients receiving chemotherapy and radiation therapy is a turning point for this paradigm change in cancer care.

The destruction of the NK and T cells resulting in lymphopenia (low levels of lymphocytes) correlated with poor prognosis of overall survival across multiple tumor types.

With our increasing knowledge of the immune system, including the discovery of T cells, NK cells and dendritic cells, and their role in cancer suppression (immuno-surveillance) and cancer growth when the tumor develops mechanisms to hide from the cytotoxic effects of NK and T cells (immune evasion), it became time to re-visit immunotherapy.

Most are familiar with the breakthrough of CPI therapy, represented by antibodies that target either PD-1, PD-L1, or other molecules that act to inhibit immune cell (specifically T cell) responses to cancer.

But even the efficacy of CPI therapies can be undermined by lymphopenia (lack of T cells), making the rescue of lymphopenia an overarching goal of my approach to cancer therapy.

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This vision, which I have pursued for decades, is the transformation in the paradigm for cancer care by treating the host and activating the immune system (NK cell and killer T cell) resulting in immunogenic cell death and inducing long-term duration of response with the generation of memory T cells and memory NK cells.

On the other hand, standards of care have been addressing the tumor itself (rather than the host immune system) with high-dose chemotherapy for short-term response gains.

A paradigm change would be to address the host’s immune system by activating the host immune system by utilizing the tumor in the body as an antigenic source to generate a long-term durable response to the activated NK cell, T cell and memory T cell.

In this way, a therapeutic cancer vaccine could be developed.

Along this journey, it has been difficult to convince academia, medical cancer centers, the FDA and even the pharmaceutical industry that existing treatment paradigms for cancer are based on misplaced assumptions utilizing high-dose chemotherapy and radiotherapy by “winning the battle but losing the war.”

In 2017, I proposed a General Investigational Plan to study a potential therapeutic cancer vaccine applicable to all tumor types to the FDA and was given an audience with the Oncology Centers of Excellence by the FDA leadership.

The hypothesis, including the request for RMAT designation presented in the plan was as follows:

“A paradigm change in cancer care is required in which a modernized treatment is based on the biology of the tumor independent of anatomy, utilizing molecular and immunological insights as to the dynamic state of the cancer in its evolution (elimination, equilibrium, and escape) and specifically tailored to the patient’s cancer altered genome, to reinstate the patient into equilibrium.

The notion that the tumor tissue itself could act as a source of both antigenicity and adjuvanticity is exploited by the NANT Cancer Vaccine – a universal therapeutic cancer vaccine that acts through the orchestration of the innate and adaptive immune system across all tumor types.

We hypothesize that the normal physiological protective immune system of Elimination can be reinstated by the NANT Cancer Vaccine, first by overcoming the immunosuppressed Escape state, followed by induction of immunogenic cell death and activation of effector immune cells, with restoration of the patient to a state of Equilibrium, a paradigm change in cancer care.”

The leadership at the FDA listened to this presentation and subsequently while denying RMAT designation, authorized my request to pursue this hypothesis by performing Phase 1 and Phase 2 clinical trials I termed “QUILT” QU antum I ntegrative L ifelong T rial across certain indications including first-line and second-line NMIBC, second-line and third-line MCC, second-line and third-line metastatic pancreatic cancer, second-line or greater GBM, third-line metastatic TNBC and third-line metastatic head & neck cancer.

I also coined the term “Quantum Oncotherapeutics” to highlight the concept that the TME is dynamic and very rapid changes occur based on the therapy we administer.

This authorization was seminal in my journey to prove the importance of NK and T cells and the need to orchestrate molecules which would induce the innate and adaptive immune system to result in durable overall survival and complete remissions.

Over the course of the past 8 years, the findings I describe below provide support that my hypothesis was correct and a universal therapeutic cancer vaccine may be possible.

For the first time in 50 years, oncologists may now have a reason to pay more attention to a complete blood count analysis of lymphocytes (NK & T cells) as the RMAT designation – granted on February 27, 2025 for ANKTIVA and PD-L1 t-haNK in combination with standard-of-care chemotherapy/radiotherapy indicated for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer – is developed.

Below is a summary of this journey.

It is my hope that the concept of ALC will begin to be recognized by oncologists and the ratio of ANC to ALC will become a key biomarker of the current status of a patient with cancer and a predictor of outcome.

The Breakthrough of NK and T Cell Rescue by IL-15 Receptor Superagonist – Overcoming Lymphopenia

The standard analysis performed by oncologists following chemotherapy is the evaluation of the CBC with the differential subset of cells that make up the circulating blood levels.

The focus of oncologists today in the review of the differential are red blood cells, platelet count and neutrophils.

Remarkably, very little to no attention is given to lymphocyte count – the very cells (killer T cells and NK cells) that are critical for killing the tumor.

Instead, in addition to platelet counts, oncologists today focus on the following subset of cells in the CBC:

• Red Blood Cells (RBCs) – to determine anemia as a consequence of the chemotherapy

• Neutrophils (ANC) – to determine the neutrophil level to avoid infection as a consequence of the chemotherapy

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Oncologists are familiar with monitoring RBCs and neutrophils since therapies are available to mitigate the consequences of anemia and neutropenia by administration of, for example, EPOGEN to manage anemia and NEUPOGEN to manage neutropenia.

Yet there is little focus on the cells of importance in the blood system that are directly involved in the killing of the tumor, lymphocytes (NK and T cells ), as reflected by the lymphocyte count and percentage of lymphocytes relative to the neutrophils.

It is likely that attention was rarely given to the lymphocyte count and the neutrophil to lymphocyte ratio (NLR) by caregivers managing cancer patients because no therapy existed to mitigate lymphopenia.

Now, we believe our IL-15 receptor superagonist ANKTIVA (also known as N-803;

molecular name nogapendekin alfa inbakicept-pmln, which has been approved for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors), provides a potential treatment for lymphopenia.

We believe that NAI may be the answer to the challenge oncologists have faced for the last 50 years, that is, how to address lymphopenia.

The efficacy of immune CPIs, while a major step forward in cancer care, depends on the presence of T cells as well as the presence of the receptor to T cells on tumors (MHC-I and MHC-II).

It stands to reason that with lymphopenia (low T cells) or MHC-I loss, T cell activity would be inhibited, and CPI therapy would fail.

However reversing lymphopenia and overcoming low NK and T cell activity could result in the rescue of T cells and CPI failures.

Just as EPOGEN and NEUOPOGEN are used across all tumor types regardless of the anatomy, we believe that NAI (proposed as ANKTIVOGEN in this potential indication), due to its ability to rescue lymphopenia by proliferation and activation of NK and T cells, has the potential to, if approved, overcome lymphopenia across all tumor types.

We believe the FDA authorization of RMAT designation for NAI and PD-L1 t-haNK in combination with standard-of-care chemotherapy/radiotherapy indicated for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer places ImmunityBio on the path to a potential paradigm change in cancer care.

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Lymphopenia in cancer and its effects on response rates to chemo and immunotherapy have been studied in detail.

Studies performed in large patient populations with advanced cancers confirm that regardless of histological subtype and treatment, global and CD4+ lymphopenia are powerful independent predictors of risk of high-grade toxicity to chemotherapy.

In addition, peripheral lymphopenia, pre-existing or induced by therapies in patients with metastatic solid tumors, strongly impacts their survival and CD4+ lymphopenia is a powerful marker of reduced survival.

Different published studies exploring the impact of global lymphopenia or NK and T cell subsets on relapse-free survival and overall survival in patients with solid tumors show lymphocyte thresholds (% lymphopenia) generally <1,000 per microliter of blood leading to elevated relative risk scores for both relapse-free survival (1.35-3.81) and overall survival (1.25-7.70).

We believe the FDA approval of ANKTIVA with BCG for treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors in 2024 and the recent RMAT designation with ANKTIVA and PD-L1 t-haNK provides the opportunity for the first FDA-approved cancer therapy (ANKTIVA in BCG Unresponsive NMIBC CIS) to be extended in patients receiving standard-of-care chemotherapy and radiotherapy, that has the potential to reverse lymphopenia – meaning the ability to resuscitate and rescue NK and T cells – the very cells of critical importance for immunogenic cell death and long-term memory against the tumor.

Through its mechanisms of action to proliferate NK and T cells (as described on its label) and therefore rescue lymphopenia, I believe ANKTIVA has the potential to be the backbone of my vision for ‘Immunotherapy 2.0’ that could launch a new era and paradigm change in the treatment of cancer across all tumor types by driving memory T and NK cells with durable remission of the disease.

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ANKTIVA overcomes tumor evasion by mitigating both the loss of T cells (lymphopenia) and the loss of the ligand to T cells on the tumor (MHC-I loss).

The mechanism of potentially overcoming cold tumors will be discussed in detail further below.

ABRAXANE – Immunogenic Cell Death in the Tumor Microenvironment (2005:

FDA Approval)

As the first step in my quest to change the paradigm of cancer care previously based on toxic high-dose chemotherapy and/or radiation, I left academia (UCLA) to develop the nation’s first albumin-bound nanoparticle of paclitaxel (nab-paclitaxel), ABRAXANE, and to institute the concept of LDMC to elicit a vaccine-like effect.

LDMC is chemotherapy not used at the MTD to kill the tumor, but rather to stress the tumor and elicit release of antigens to allow the killer cells surrounding the tumor (macrophages, T cells and NK cells), to induce immunogenic cell death.

Even today, the concept of albumin-bound therapy to concentrate drug at the tumor site is not always fully appreciated by the oncology community.

ABRAXANE was developed to exploit the biology of the concept of transcytosis whereby the transport of albumin-bound paclitaxel across the endothelial blood vessel layer to the TME is accomplished through the gp60 receptor and the Caveolin pathway leading to entry of paclitaxel in the TME and the production of stress molecules in the tumor (DAMPs), while at the same time activating the killer macrophages (M2 suppressive macrophages to M1 killer macrophages).

ABRAXANE was approved by the FDA in 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic diseases or relapse within six months of adjuvant chemotherapy and now also has FDA approval for patients with lung and pancreatic cancer in certain indications.

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ANKTIVA – IL-15 Receptor Superagonist Rescuing Lymphocytes and Overcoming MHC-I Loss (2024:

FDA Approval)

With ABRAXANE as the first pillar in this quest to change the paradigm of care, I then turned my attention to addressing lymphopenia and unleashing the “triangle offense” via the IL-15 receptor superagonist ANKTIVA.

In 2024, ANKTIVA with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors was approved by the FDA, who authorized the description of the mechanism of action in the label as:

Nogapendekin alfa inbakicept-pmln is an IL-15 receptor agonist.

IL-15 signals through a heterotrimeric receptor that is composed of the common gamma chain (γc) subunit, the beta chain (βc) subunit, and the IL-15-specific alpha subunit, IL-15Rα.

IL-15 is trans-presented by the IL-15 receptor α to the shared IL-2/IL-15 receptor (βc and γc) on the surface of CD4+ and CD8+ T cells and NK cells.

Binding of nogapendekin alfa inbakicept-pmln to its receptor results in proliferation and activation of NK, CD8+, and memory T cells without proliferation of immuno-suppressive T-reg cells.

In vivo, intravesicular nogapendekin alfa inbakicept-pmln alone or in combination with BCG showed anti-tumor activity when compared to BCG alone, in a carcinogen-induced model of bladder cancer in immunocompetent rats.

I believe this potentially universal therapeutic vaccine, sometimes referred to as NCV (U.S.

Patent #US11071774-B2), could be able to coordinate the release of antigens from tumor cells (DAMPs/neoantigens and/or shared tumor-associated antigens, TAAs) or provision of vaccine antigens with support for immune-cell activity, including cells of both the innate and adaptive immune systems, to achieve a vaccine-like effect.

ANKTIVA, due to its mechanism of proliferating and activating innate (macrophages, NK cells, dendritic cells) and adaptative (T cells, iNKT cells, and memory T cells) immune cells provides the vital stimulus needed to establish immune memory.

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Thus, I believe ANKTIVA has the potential to become the backbone for a cancer vaccine not only to potentially cure cancer (long-term duration free of disease) but also to prevent cancer.

An example of the possibility of prevention is in subjects with Lynch Syndrome, a genetic condition that puts them at significantly higher risk for cancer, and with an earlier age of onset.

Currently, ANKTIVA plus vaccines that deliver tumor associated antigens via adenovirus, relevant to Lynch Syndrome are being tested in clinical trials with subjects with Lynch Syndrome for their ability to prevent cancer onset.

If efficacious, this novel treatment could help support that a universal cancer vaccine is indeed possible.

Quantum Oncotherapeutics – A Potential Universal Therapeutic Cancer Vaccine

Changing the paradigm and convincing oncologists of the need to avoid high-dose chemotherapy and implement a treatment protocol that activates the patient’s immune system rather than destroying the NK cells and T cells remains a difficult task even today.

In 2017, the FDA allowed ImmunityBio (formerly NantKwest and NantCell) to initiate a series of transformative clinical trials in which the concept of inducing immunogenic cell death (ICD) was pursued.

These trials entitled “QUILT” QUantum Integrative Lifelong Trials were seminal in the pursuit of a universal cancer vaccine.

The clinical protocols shared an approach that followed my vision of inducing DAMPs, avoiding high-dose chemotherapy, educating T cell via dendritic cell activation and inducing NK, CD4+ and CD8+ T cell proliferation in combination with off-the-shelf CAR-NK cell therapy to overcome immunosuppressive T-reg cells and myeloid-derived suppressive cells (MDSCs).

The findings from the QUILT trials have confirmed the validity of the NCV approach.

In 2022, I was honored to present the concept of “Quantum Oncotherapeutics” providing updates and receiving authorization to proceed with the QUILT trials and by 2025 met with the FDA to present the update of these trials.

The Challenges of Checkpoint Failure Facing Oncologists:

Immunotherapy 2.0 Beyond Checkpoints

By 2024, the FDA had approved the use of CPIs (pembrolizumab, nivolumab, etc.) across 17 different tumor types.

However, at the 2024 ASCO Annual Meeting I believe it became apparent that responses to CPIs were frequently fleeting and that CPIs were not effective in so-called “cold tumors.” The cold tumor is defined as lacking sufficient T-cell infiltration or activity of the T cells, even with use of a CPI, in the TME, and the loss of MHC-I, the binding site on the tumor for the T-cell receptor.

Thus, the lack of effect in cold tumors is driven by fewer T cells (lymphopenia) and selection of cancer cell clones without the receptor for T cells to bind to MHC-I (MHC-I loss).

Given these dynamics, it is not surprising that CPIs alone often fail or elicit only transient responses.

Overcoming Tumor Evasion and Converting a Cold Tumor to a Hot Tumor

The addition of ANKTIVA not only rescues T cells, but also activates NK cells that have the ability to recognize tumor cells without MHC-I expression and, as a result of increased interferon-γ (IFN-γ) secretion by the activated NK cells, also has the potential to restore MHC-I expression.

All of these activities act to rescue CPIs.

Thus, the combination of ANKTIVA plus a CPI represents Immunotherapy 2.0.

A depiction of how ANKTIVA has the potential to convert a cold tumor to a hot tumor and rescues CPIs is provided below.

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The loss of MHC-I molecules serves as a mechanism for tumor evasion and progression during CPI therapy.

This phenomenon can be understood through the lens of Darwinian selection, where tumors that are resistant to either chemotherapy or chemo-immunotherapy emerge due to the loss of MHC-I receptors on tumor cells, which are essential for T cell recognition.

These highly selected resistant cells, characterized by MHC-I loss, subsequently become targets for NK cells.

NK cells are specifically designed to identify and eliminate cells that lack MHC-I expression, a process known as “missing-self” recognition.

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The evasion of tumors from checkpoint therapy through the loss of MHC-I molecules leads to the generation of MHC-I negative, or “cold” tumors.

Initially, the tumor cells are “hot” and recognized by T cells activated by CPIs.

However, with the loss of MHC-I, these tumor cells evade T cell detection, becoming “cold” and resulting in checkpoint therapy failure and subsequent tumor progression.

An MHC negative cold tumor cell which has evaded T cell detection and hence led to progression despite treatment with CPIs is now the target of NK cells.

NK cells cytotoxicity is independent of MHC-I status and independent of PD-L1 status on the tumor cell.

Thus, if NK cells could be activated and proliferated, NK cells could kill these Darwinian-selected resistant cancer cells and rescue CPIs.

The NK cell recognizes the MHC negative cold tumor and converts the tumor from hot to cold through IFN-γ stimulation.

As a consequence, MHC-I and MHC-II are re-expressed on the tumor cell, making the cell recognizable by T cells.

This dynamic activity can be enhanced by proliferation of NK, CD4+ and CD8+ T cells through IL-15 stimulation of the IL-15 receptor on NK, CD4+ and CD8+ T cells.

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ANKTIVA, an IL-15 receptor superagonist, stimulates the IL-15 receptor on natural killer cells resulting in proliferation of the NK cell and conversion of the cold tumor to hot by the NK cell recognizing the MHC negative tumor and converting the cold tumor to hot.

This activity of reactivating T cells allows the rescue of CPIs against PD-1.

ANKTIVA rescues and restores CD8+ killer T cells and memory T cells by converting MHC negative (cold) to MHC positive (hot) tumors through IL-15 stimulated NK cell activation and IFN-γ secretion with durable response and prolonged overall survival.

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QUILT Studies Validate NCV with ANKTIVA as the Backbone

I presented findings from completed QUILT studies during a 2025 program review meeting with the FDA, including the achievement of complete remissions in late-stage and advanced tumors of many types, such as NMIBC, MCC, TNBC, pancreatic cancer and head & neck cancer, validating the concept of eliciting immunogenic cell death rather than the tolerogenic cell death induced by current standards of care.

A summary of the complete remissions is shown in the image below.

ImmunityBio Platforms - The Development of a Universal Therapeutic Cancer Vaccine

Based on the vision of activating the patient’s immune system, the company continues its efforts to demonstrate that a universal cancer vaccine that leverages the power of its platforms – backbone ANKTIVA, off-the-shelf and autologous NK-cell-based therapies, adenovirus-vectored delivered vaccines, and other technologies – provide benefit and hope not only for patients with cancer but also for those with a high risk of developing cancer.

Table of Conten t s

Select Clinical Development Program 2025+

The future of immunotherapy appears bright and I continue my quest to drive towards a therapeutic vaccine across multiple tumor types where patients do not suffer the adverse events of high-dose chemotherapy and high-dose radiotherapy.

We have made and are targeting multiple submissions to the FDA in 2025 and beyond.

In February 2025, the FDA authorized an EAP allowing us to provide rBCG developed by Serum Institute to urologists to address the TICE BCG shortage in all settings where TICE BCG is approved.

In addition, as announced on February 27, 2025, the FDA has granted ImmunityBio RMAT designation for ANKTIVA and PD-L1 t-haNK in combination with standard-of-care chemotherapy/radiotherapy indicated for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer.

This RMAT designation follows clinical data of ALC and significant overall survival correlations in QUILT trials across multiple tumor types including third-line or greater metastatic pancreatic cancer, checkpoint relapsed NSCLC, and supportive data from healthy volunteers.

The reversal of lymphopenia by ImmunityBio’s IL-15 receptor superagonist is consistent with the mechanism of action of ANKTIVA demonstrating proliferation and activation of NK cells, CD4+ T cells, CD8+ T cells, and memory T cells without upregulation of suppressive T reg cells and approved in the ANKTIVA label (approved for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors).

ImmunityBio intends to submit a BLA for the indication of reversal of lymphopenia in patients receiving standard-of-care chemotherapy and/or radiation and for the treatment of locally advanced or metastatic pancreatic cancer which includes the first-in-class CAR-NK (PD-L1 t-haNK), and to provide data from fully enrolled clinical trials in metastatic pancreatic cancer (QUILT 88) and in checkpoint relapsed NSCLC (QUILT 3055, NSCLC Cohort) patients, as well as lymphopenia reversal across multiple tumor types (QUILT 3055, all Cohorts), with supportive data of lymphocyte proliferation in healthy volunteers (QUILT 1004).

In addition, ImmunityBio intends to file an EAP for ANKTIVA and PD-L1 t-haNK in combination with standard-of-care chemotherapy/radiotherapy and submit the protocol to the FDA.

Table of Conten t s

ImmunityBio Business, Strategy and Products

ImmunityBio is a vertically-integrated commercial stage biotechnology company developing next-generation therapies that bolster the natural immune system to defeat cancers and infectious diseases.

The company’s range of immunotherapy platforms, alone and together, act to drive an immune response with the goal of creating durable immune memory generating safe protection against disease.

We are applying our science and platforms to treating cancers, including the development of potential cancer vaccines, as well as developing immunotherapies and cell therapies that we believe sharply reduce or eliminate the need for standard high-dose chemotherapy.

These platforms and their associated product candidates are designed to be more effective, accessible, and easily administered than current standards of care in oncology and infectious diseases.

We seek to become a leading global immunological therapeutics company by creating next-generation therapies to address serious unmet needs within urologic and other cancers as well as infectious diseases.

To achieve this goal, the key elements of our strategy include:

• advancing the commercialization of ANKTIVA as an integral component of immunotherapy combinations, including those with CPIs and cell therapy;

• accelerating product candidates generated from our immunotherapy platforms with registrational intent to address difficult-to-treat oncological and infectious disease indications in large market segments;

• continuously refining our pipeline and investing in high-value discovery, development, and manufacturing capabilities for our next generation product candidates;

• continuing to prospect, license, and acquire technologies to complement and strengthen our platforms and product candidates, both as single agent and combination therapies, in order to optimize responses of the innate and adaptive immune systems to generate cellular memory against multiple tumor types and infectious diseases;

• cultivating new and expanding existing collaborations for our multi-stage pipeline to reach global scale efficiently.

Our Approved Product – ANKTIVA

Our lead biologic product ANKTIVA is a novel first-in-class IL-15 receptor superagonist antibody-cytokine fusion protein.

On April 22, 2024, the FDA approved our product, ANKTIVA with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors (the “approved product”).

ANKTIVA was approved with a label indicating an immunological mechanism of action which proliferates and activates NK, CD8+ and memory T cells without the proliferation of immunosuppressive T-reg cells leading to the establishment of memory T cells.

We began commercial distribution of our approved product in May 2024.

We believe there is potential for ANKTIVA to become a therapeutic foundation across all phases of treatment, including in adjunctive therapy, to amplify, reactivate or extend the efficacy of standard of care.

ANKTIVA is being clinically evaluated in multiple oncology indications.

We believe that other oncology indications with registration potential for ANKTIVA include other types of NMIBC ( BCG-unresponsive papillary, BCG-naïve CIS and BCG-naïve papillary), lung, colorectal, pancreatic, prostate and ovarian cancers, and GBM and NHL.

Data from multiple clinical trials suggest ANKTIVA has potential to enhance the activity of therapeutic mAbs, including CPIs (e.g., pembrolizumab/Keytruda), across a wide range of tumor types, including lung cancer.

Further, ANKTIVA has been observed to increase lymphocyte count in healthy adults, making it a potential therapy to rescue lymphopenia.

We believe that the FDA authorization of RMAT designation for ANKTIVA and PD-L1 t-haNK in combination with standard-of-care chemotherapy/radiotherapy indicated for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer may lead to a potential paradigm change in cancer care.

We are also exploring or pursuing several other studies of ANKTIVA in combination with our other product candidates, including in prostate cancer (ANKTIVA in combination with hAd5 PSA), colon cancer (ANKTIVA in combination with hAd5 TriAd), and NHL (ANKTIVA in combination with rituximab).

We are also exploring ANKTIVA in infectious diseases, including HIV and long COVID.

Table of Conten t s

Key Catalysts for ANKTIVA

The following is a summary of selected significant developments affecting our business that occurred since the filing of our Quarterly Report dated September 30, 2024 with the SEC on November 12, 2024:

• ANKTIVA received a J-code (J9028) assigned by the CMS in the U.S.

for ANKTIVA (Injection, nogapendekin alfa inbakicept-pmln, for intravesical use, 1 microgram), which became effective on January 1, 2025.

• With a permanent J-code awarded in January 2025, our February 2025 ANKTIVA unit sales volume grew 97% over unit sales volume in December 2024 and 67% over unit sales volume in January 2025.

• ANKTIVA is now widely accessible to patients through commercial and government insurance programs (VA, DoD, Medicare).

To date, commercial and governmental insurance cover over 240 million lives for ANKTIVA.

• We completed the submission of MAAs for the treatment of patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors for ANKTIVA in combination with BCG to the MHRA in the UK in November 2024 and to the EMA in the EU in December 2024.

The MHRA validated and accepted the MAA for review in February 2025, while the EMA accepted the MAA for review in January 2025.

We are in continued dialogue for requests for information from both the MHRA and EMA, with the potential for approval in the UK and EU by 2026.

• In collaboration with Serum Institute, and in connection with our exclusive global supply arrangement that we announced during 2024, in February 2025 the FDA authorized an EAP allowing us to provide rBCG developed by Serum Institute to urologists to address the TICE BCG shortage in all settings where TICE BCG is approved, and we are also testing rBCG in an FDA-approved clinical trial in the U.S.

Serum Institute’s GMP capacity to manufacture large-scale volumes of rBCG, already tested for safety and efficacy in clinical trials in Europe in subjects with NMIBC, aims to address the shortage of TICE BCG, which we believe will help to ensure a reliable supply for patients in need.

This initiative underscores our commitment to addressing critical supply issues and expanding the opportunity for patients and physicians to have access to high quality and quantities of BCG to initialize and maintain treatments for bladder cancer, subject to regulatory approvals.

We expect to begin shipments of rBCG pursuant to the EAP during the first quarter of 2025.

• In January 2025, we announced a collaboration and supply agreement with BeiGene, Ltd.

(to be renamed to BeOne Medicines, Ltd.), a global oncology company, to conduct a confirmatory randomized Phase 3 clinical trial (ResQ201A-NSCLC), combining BeOne’s tislelizumab, a PD-1 CPI, and our ANKTIVA (nogapendekin alfa inbakicept-pmln) product.

The Phase 3 ResQ201A-NSCLC study aims to confirm the efficacy and safety of combination ANKTIVA plus CPI therapy previously demonstrated in the QUILT 3055 trial and provide evidence of the potential for these two immunotherapeutic agents to improve overall survival in patients with advanced or metastatic NSCLC who have acquired resistance to immune CPI therapy.

• On February 27, 2025, the FDA granted us RMAT designation for ANKTIVA and CAR-NK (PD-L1 t-haNK) in combination with standard-of-care chemotherapy/radiotherapy indicated for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer.

The reversal of lymphopenia by our IL-15 receptor superagonist is consistent with the mechanism of action of ANKTIVA demonstrating proliferation and activation of NK cells, CD4+ T cells, CD8+ T cells, and memory T cells without upregulation of suppressive T-reg cells and approved in the ANKTIVA label (approved for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors).

We intend to submit a BLA for the indication of reversal of lymphopenia in patients receiving standard of care chemotherapy and/or radiation and for the treatment of locally advanced or metastatic pancreatic cancer which includes the first-in-class CAR-NK (PD-L1 t-haNK), and to provide data from fully enrolled clinical trials in metastatic pancreatic cancer (QUILT 88) and in checkpoint relapsed NSCLC (QUILT 3055, NSCLC Cohort) patients, as well as lymphopenia reversal across multiple tumor types (QUILT 3055, all Cohorts), with supportive data of lymphocyte proliferation in healthy volunteers (QUILT 1004).

In addition, we intend to file an EAP for ANKTIVA and PD-L1 t-haNK in combination with standard of care chemotherapy/radiotherapy and to submit the protocol to the FDA.

Table of Conten t s

2025 Platforms and Indications

Our proprietary platforms for the development of biologic products and product candidates include:

Our Next-Generation Platforms

Cytokine Fusion Proteins

DNA and Vaccine Vectors

hAd5 (PSA, Brachyury, CEA, MUC1, HPV [E6/E7], neoantigens, nucleocapsid)

Cell Therapies

M-ceNK (autologous, allogeneic)

Indications (Current Prioritized Studies)

BCG-Unresponsive NMIBC with CIS (approved)

BCG-Unresponsive NMIBC Papillary

BCG-Naïve NMIBC with CIS

rBCG in NMIBC

Non-Small Cell Lung Cancer

ImmunityBio, Inc.

(“ImmunityBio,” the “Company,” “we,” “us,” or “our”) is a biotechnology company focused on innovating, developing, and commercializing next-generation immunotherapies designed to activate the patient’s immune system and deliver durable protection against cancer and infectious diseases.

Our approach harnesses both the adaptive and innate immune systems with the goal of restoring immune function and generating lasting immunological memory in patients.

At the core of our strategy is the Cancer BioShield ™ platform, which is designed to stimulate critical lymphocytes, including natural killer (NK) cells, cytotoxic T cells, and memory T cells via our proprietary IL-15 superagonist, ANKTIVA ® (nogapendekin alfa inbakicept).

Our Cancer BioShield platform is anchored by this antibody-cytokine fusion protein and is complemented by a portfolio that includes adenovirus-vectored vaccines, allogeneic (off-the-shelf) and autologous NK-cell therapies, and additional immunomodulators intended to promote immunogenic cell death and support durable immune responses while potentially reducing reliance on high-dose chemo-radiation therapy.

ANKTIVA is our lead biologic product and a first-in-class IL-15 receptor superagonist antibody-cytokine fusion protein.

We are commercializing ANKTIVA for the treatment of BCG-unresponsive NMIBC CIS with or without papillary tumors.

ANKTIVA has received FDA Breakthrough Therapy designation for use in BCG-unresponsive NMIBC CIS in adult patients with or without papillary tumors.

ANKTIVA is now approved in the U.S., UK, and Saudi Arabia for BCG-unresponsive NMIBC CIS with or without papillary tumors.

In February 2026, the European Commission granted conditional marketing authorization in the EU for ANKTIVA for the same indication.

In addition, ANKTIVA is conditionally approved in Saudi Arabia, for use in combination with a CPI, for the treatment of adult patients with metastatic NSCLC whose disease has progressed following standard-of-care therapy.

The approved labels highlight ANKTIVA’s ability to simultaneously activate NK cells, cytotoxic T cells, and memory T cells.

ANKTIVA in combination with our CAR-NK therapy (PD-L1 t-haNK) has received RMAT designation from the FDA for use in combination with standard-of-care chemotherapy/radiotherapy for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer.

Separately, the FDA has authorized an EAP for ANKTIVA to treat lymphopenia in adult patients with refractory or relapsed solid tumors, regardless of tumor type, who have progressed following first-line standard-of-care treatment, including chemotherapy, radiation, or immunotherapy.

The EAP includes patients with solid tumors who have failed first-line therapy and have a low ALC (ALC <1,000/μL).

We are seeking to expand development of ANKTIVA in combination with current standard-of-care therapies across multiple solid and liquid tumor indications including:

• BCG-naïve NMIBC;

• BCG-unresponsive NMIBC with papillary tumors;

• Second-line NSCLC;

• First-line NSCLC;

• Glioblastoma;

• Indolent non-Hodgkin lymphoma, including Waldenström macroglobulinemia;

• Pancreatic cancer;

Chemotherapy Radiation Lymphopenia

Lynch Syndrome

Hematological Malignancies (Liquid Tumors)

Glioblastoma Multiforme

Non-Hodgkin Lymphoma

Ovarian Cancer

• Prostate cancer;

Universal Nucleocapsid Vaccine

Our proprietary platforms for the development of biologic products and product candidates include:

(i) cytokine fusion proteins, (ii) vaccine vectors, and (iii) cell therapies.

As of December 2024, our platforms have generated nine first-in-human therapeutic agents (including one agent approved by the FDA) that are currently or planned to be studied in clinical trials in liquid and solid tumors.

The indications in the table above are among the most frequent and lethal cancer types and where there are high failure rates for existing standards of care or no available effective treatment.

We are constantly monitoring and prioritizing clinical development based upon the availability of our resources and the efficacy and market developments of our competitors’ products and product candidates, among other factors.

Our platforms and their associated approved product and product candidates are designed to attack cancer and infectious pathogens by activating both the innate immune system, including NK cells, dendritic cells, and macrophages, as well as the adaptive immune system comprising B and T cells, in an orchestrated manner.

The goal of this potentially best-in-class approach is to generate immunogenic cell death thereby eliminating rogue cells from the body whether they are cancerous or virally-infected.

Our ultimate goal is to overcome the limitations of current treatments, such as CPIs, by turning immunologically cold, MHC-deficient tumors into hot tumors, and/or reducing the need for standard high-dose chemotherapy in cancer by employing a coordinated approach to establish “immunological memory” that confers long-term benefit for the patient.

Table of Conten t s

Our Next-Generation Platforms

• Ovarian cancer.

In addition, ANKTIVA has been selected by the NCI for evaluation in a cancer prevention study in patients with Lynch syndrome, and we are evaluating the combination of ANKTIVA with other agents in colorectal cancer.

The company is also supporting an ongoing EAP for rBCG to help address U.S.

supply constraints.

We are also establishing or conducting trials in multiple myeloma, HCC, and TNBC.

Commercial Performance

We began commercial distribution of ANKTIVA in May 2024 following FDA approval.

The following table summarizes our commercial performance through December 31, 2025:

Metric Value Period

Net Product Revenue ~$113 million Full Year 2025

Year-Over-Year Growth ~700% 2025 vs.

Unit Sales Growth ~750% 2025 vs.

Q4 2025 Revenue $38.3 million 20% sequential, 431% YoY

Lives Covered >240 million As of December 2025

Reimbursement:

ANKTIVA received a permanent J-code (J9028) from CMS, effective January 1, 2025, for “Injection, nogapendekin alfa inbakicept, for intravesical use, 1 microgram.”

Regulatory Approvals

Jurisdiction Indication Status

United States (FDA) BCG-unresponsive NMIBC CIS +/- papillary Approved (Apr.

United Kingdom (MHRA) BCG-unresponsive NMIBC CIS +/- papillary Approved (Jul.

Saudi Arabia (SFDA) BCG-unresponsive NMIBC CIS +/- papillary Approved (Jan.

Saudi Arabia (SFDA) Progressing metastatic NSCLC + CPI Conditionally approved (Jan.

European Union (EMA) BCG-unresponsive NMIBC CIS +/- papillary Conditionally approved (Feb.

As of February 2026, ANKTIVA has received regulatory approval in four jurisdictions spanning two therapeutic indications (bladder cancer and lung cancer).

To our knowledge, based on publicly available information, the SFDA’s conditional approval of ANKTIVA in combination with CPIs for metastatic NSCLC is the first regulatory approval for an IL-15 receptor superagonist in lung cancer.

The European Commission granted conditional marketing authorization for ANKTIVA with BCG in BCG-unresponsive NMIBC CIS with or without papillary tumors, which is the first approval of a therapeutic in this indication in Europe.

ANKTIVA is now authorized for use in 33 countries.

SCIENTIFIC RATIONALE

The Lymphopenia Challenge in Oncology

Lymphopenia, defined as the severe depletion of cancer-killing NK and T cells, represents a critical and widely unaddressed problem in oncology.

The ALC is a routine measurement in complete blood counts that carries independent prognostic weight across tumor types.

Based on published literature and internal estimates derived from American Cancer Society incidence data and treatment patterns, lymphopenia affects a substantial portion of U.S.

cancer patients annually.

Standard treatments, including radiotherapy, chemotherapy, steroids, and certain immunotherapies, can induce or worsen this condition.

Clinical Significance:

Mortality Risk of Low ALC in General Population, All Causes & Cardiovascular Disease

In 2019, Zidar et al., published in JAMA, “Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population” and reported that low lymphocyte levels are associated with reduced survival in the U.S.

general population.

Their study highlighted that “ based on these findings, patients with lymphopenia, especially those with other immunohematologic abnormalities, may have excess mortality risk;

these patients are readily identifiable because tests of lymphocyte levels often occur during routine medical encounters.” Furthermore, the importance of this finding was emphasized by the following statement, “ Immune dysregulation can increase the risk of infection, malignant neoplasms, and cardiovascular disease, but improved methods are needed to identify and quantify immunologic hazard in the general population .”

Of note, the risk mortality from all causes and from heart and cerebrovascular disease consistently rises when the ALC levels fall from normal to below 2,000.

These findings emphasize the need to protect the immune system and maintain ALC levels even in the general population.

The economic significance of increased mortality and reduced longevity is significant.

In the Nature publication by Scott et al., entitled, “The Economic Value of Targeting Aging”, the authors concluded that “ a slowdown in aging that increases life expectancy by 1 year is worth US$38 trillion, and by 10 years, US$367 trillion.

Ultimately, the more progress that is made in improving how we age, the greater the value of further improvements.”

Association of Lymphopenia with Mortality in General Population

Solid lines indicate hazard ratio point estimates;

dotted lines, 95% CI

Zidar DA et al., Figure 2.

Association of Lymphopenia with Mortality

Zidar DA, Al-Kindi SG, Liu Y, et al.

Association of lymphopenia with risk of mortality among adults in the US general population.

JAMA Network Open.

2019;2(12):e1916526.

doi:10.1001/jamanetworkopen.2019.16526

Furthermore, in the Zidar et al., study of over 31,000 Americans, a clear demonstration of survival related to lymphocyte levels is seen in this graph below.

When lymphocyte levels fall between 0.3 to 1.5, the survival rate decreases.

Lymphocyte Levels Associated with Survival

Zidar et al., Supplemental Figure 1

Zidar DA, Al-Kindi SG, Liu Y, et al.

Association of lymphopenia with risk of mortality among adults in the US general population.

JAMA Network Open.

2019;2(12):e1916526.

doi:10.1001/jamanetworkopen.2019.16526

Mortality Risk with Low ALC in Cancer

Additionally, the risk of death from cancer increases when the absolute lymphocyte count level falls below 2.0.

Association with Lymphopenia with Mortality in Patients with Cancer

Solid lines indicate hazard ratio point estimates;

dotted lines, 95% CI

Zidar DA et al., Figure 2.

Associated of Lymphopenia with Mortality

Zidar DA, Al-Kindi SG, Liu Y, et al.

Association of lymphopenia with risk of mortality among adults in the US general population.

JAMA Network Open.

2019;2(12):e1916526.

doi:10.1001/jamanetworkopen.2019.16526

Multiple peer-reviewed studies have shown that severe lymphopenia (ALC <1,000 cells/μL) is associated with a significantly increased risk of mortality in patients with solid tumors.

Large retrospective analyses have shown that patients with peripheral lymphopenia experience markedly higher rates of high-grade chemotherapy toxicity and reduced overall survival, with published relative risk estimates for relapse-free survival ranging from 1.35 to 3.81-fold and for overall survival from 1.25 to 7.70-fold compared with patients maintaining adequate lymphocyte levels.

Of note, this association with lymphopenia and statistically increased mortality occurs regardless of tumor type as shown by Ménétrier-Caux C et al., In this publication entitled, “Lymphopenia in Cancer Patients and its Effects on Response to Immunotherapy:

an opportunity for combination with Cytokines?”, the authors review “ the current knowledge on the incidence and significance of lymphopenia in cancer patients, and discuss therapeutic strategies to restore lymphocyte numbers.”

Treatment Gap:

While oncologists have established supportive therapies such as erythropoietin-stimulating agents and granulocyte colony-stimulating factors to manage chemotherapy-induced anemia and neutropenia, respectively, no FDA-approved therapy has been specifically indicated for the treatment of lymphopenia in cancer patients.

Interleukin-15 (IL-15) was ranked by the NIH and NCI as the number 1 cytokine with the potential to cure cancer.

The findings of this working group was published in 2008 by Cheever M., entitled, “Twelve Immunotherapy Drugs that Could Cure Cancers.”

The NIH undertook decades of research to develop this IL-15 cytokine as a therapeutic and in 2015, the understanding of the shared and contrasting roles of IL-2 versus IL-15 was published by Thomas A.

Waldmann, MD (NIH Distinguished Investigator) highlighting the decades long focus on IL-2 and the neglect of IL-15 for therapeutic lymphopenia correction as a consequence of both historical timing and incomplete mechanistic understanding that only recent insights in immunobiology had begun to correct.

Biological Misunderstanding and Overlap Between IL-2 and IL-15

Pharmacological Development Based on Incorrect Assumption that IL-2 was the Key Cytokine For Cancer Therapy

Discovery and Development of IL-2 and IL-15:

IL-2 was discovered in 1976 as “T-cell growth factor,” and by the 1980s, became the first cytokine to be evaluated in humans for cancer immunotherapy.

High-dose recombinant IL-2 (aldesleukin) was FDA-approved in the 1990s for metastatic renal cell carcinoma (1992) and metastatic melanoma (1998) which established a precedent and clinical infrastructure around IL-2.

IL-15 was only discovered in 1994, nearly two decades after IL-2 and was approved for the treatment of NMIBC in 2024.

Biological Misunderstanding and Overlap Between IL-2 and IL-15 Accounting for the Delay in Development of IL-15:

IL-2 and IL-15 share two receptor subunits (IL-2/15Rβ and γc), which led early researchers to assume overlapping biological effects since the receptor expressed on the surface of T cells is commonly referred to as the IL-2 receptor.

However, their distinct α-receptors (IL-2Rα vs.

IL-15Rα) and modes of presentation (cis vs.

trans) result in profoundly different immunological outcomes (see Figure 1 below).

IL-2 primarily stimulates Tregs and not NK cells, leading to immune contraction and immune evasion.

IL-15, in contrast, preferentially supports CD8+ memory T cells and NK cells while avoiding Treg expansion making it biologically superior for sustained immune responses—but this was only appreciated later through mechanistic studies.

This biological misunderstanding partially explains why the treatment of lymphopenia by stimulating NK and T cells to date (2025) remained unaddressed.

The decades-long focus on IL-2 and neglect of IL-15 for therapeutic lymphopenia correction reflect both historical timing and incomplete mechanistic understanding that only recent developments in immunobiology have begun to correct.

With this insight, the cytokine fusion protein ANKTIVA was developed and studies in healthy volunteers demonstrated the mechanism of action of proliferating NK, CD4+ CD8+ T cells without up-regulating Tregs.

Healthy Volunteers with ANKTIVA (IL-15 Superagonist):

These findings were published in the Journal of Immunology (March 2022) showing that ANKTIVA had a greater than 20-fold longer in vivo half-life than native IL-15.

Furthermore, NK cells and CD8+ T cells were stimulated with sustained increase over 2 weeks.

Addressing Cold Tumors and Immune Evasion

Cancer cells can evade immune detection through “immune escape,” particularly by losing MHC-I expression on their cell surface.

Tumors lacking MHC-I expression (“cold tumors”) cannot be recognized by T cells, which may limit the efficacy of CPI therapy.

This phenomenon has been characterized in published literature as a mechanism of primary and acquired resistance to immunotherapy.

ANKTIVA’s mechanism of action addresses this challenge through several pathways:

NK-Cell Activation:

ANKTIVA activates NK cells, which recognize and attack cells lacking MHC-I expression through “missing-self” recognition, a well-characterized immune surveillance mechanism.

Interferon-gamma Release:

Activated NK cells secrete interferon-gamma, which, as shown in published studies, stimulates MHC-I re-expression on tumor cells.

Tumor Transformation:

Through this mechanism, tumors may be converted from MHC-negative (“cold”) to MHC-positive (“hot”), potentially making them recognizable by T cells.

Memory T Cell Generation:

ANKTIVA’s IL-15 agonist activity supports the establishment of memory T cells, which may provide long-term immune surveillance.

Limitations of Current Checkpoint Inhibitor Therapy

The development of CPIs represented a major advance in cancer treatment.

However, published data indicate that patient responses may be limited:

• Primary resistance:

Approximately 40-60% of patients do not respond to CPI monotherapy, according to published clinical trial data.

• Acquired resistance:

Many initial responders eventually experience disease progression.

• Limited efficacy in tumors lacking T cell infiltration.

• Dependence on adequate lymphocyte populations for optimal activity.

ANKTIVA is designed to address these limitations by restoring lymphocyte counts depleted by prior therapies, activating NK cells to target MHC-negative tumor cells, and generating memory T cells to support potentially durable responses.

Although ANKTIVA for use in combination with CPIs has received conditional approval from the SFDA in Saudi Arabia for the treatment of adult patients with metastatic NSCLC whose disease has progressed following standard-of-care therapy, there can be no assurance that ANKTIVA will be effective in overcoming CPI-resistance or that it will receive additional regulatory approvals.

“ Risk Factors— Our clinical trials may fail to adequately demonstrate the safety and efficacy of our product candidates, which would prevent or delay regulatory approval and commercialization of other product candidates ” in this Annual Report.

We aim to become a leading global immunotherapy company by developing therapies to address serious unmet needs in oncology and infectious diseases.

The key elements of our strategy include:

• building commercial infrastructure and expanding partnerships to support the global adoption of ANKTIVA as a backbone lymphocyte-stimulating agent.

With FDA approval in April 2024, a permanent J-code (J9028) effective in January 2025, payer coverage exceeding 240 million lives in the U.S., and international approvals in the UK, EU, and Saudi Arabia, we are establishing global access pathways for patients, including new commercial partnerships with Accord Healthcare in the EU, and Cigalah Healthcare and Biopharma in the Middle East;

• accelerating product candidates generated by our Cancer BioShield platform toward potential registration in difficult to treat oncological and infectious disease indications in large market segments, including oncology-induced lymphopenia, bladder, lung and pancreatic cancers, and GBM and NHL;

• continuously refining our pipeline based on clinical data, regulatory feedback, competitive landscape, and resource allocation;

• continuing to prospect, license, and acquire technologies to complement and strengthen our Cancer BioShield platform and product candidates—whether used as single agents or in combination—in order to optimize responses of the innate and adaptive immune systems to generate cellular memory against multiple tumor types and infectious diseases;

• cultivating new partnerships and expanding collaborations to advance ANKTIVA and our pipeline efficiently.

OUR APPROVED PRODUCT

Product Description and Mechanism

ANKTIVA is a first-in-class IL-15 receptor superagonist antibody-cytokine fusion protein.

The FDA approved ANKTIVA with BCG in April 2024 for the treatment of adult patients with BCG-unresponsive NMIBC CIS with or without papillary tumors.

ANKTIVA was approved with a label indicating an immunological mechanism of action that proliferates and activates NK cells, CD8+ T cells, and memory T cells without the proliferation of immunosuppressive Tregs.

The cytokine IL-15 supports the immune system by influencing the development, maintenance, and function of NK cells and CD8+ killer T cells.

ANKTIVA consists of an IL-15 mutant (IL-15N72D) fused with an IL-15Rα , which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells.

Pharmacokinetic and Pharmacodynamic Properties

QUILT-1004 (Healthy Volunteers):

A Phase 1 study in 14 healthy adult volunteers evaluated the pharmacokinetic, safety, and immunologic profile of ANKTIVA.

Subjects received two subcutaneous doses (10 μg/kg followed 24 days later by 20 μg/kg) and were monitored for nine consecutive days after each dose.

Key findings from this study:

• Serum half-life of approximately 20 hours (compared to <1 hour for recombinant IL-15)

• Peak concentrations occurring 10-15 hours post-dose

• Well-tolerated, with the most common adverse events being mild injection-site reactions, chills, and pyrexia

• No grade 3 or higher or serious adverse events reported

• Greater than 3-fold increase in absolute NK cell count persisting for 24 days or more

• 22-fold rise in proliferating NK cells (Ki-67 staining)

• 27-fold increase in CD8+ T cells

• 11-fold rise in CD4+ T cells

• No expansion of immunosuppressive Tregs

• Mean ALC exceeding 1,200 cells/μL in the majority of participants

These pharmacodynamic outcomes in healthy volunteers provide mechanistic support for the lymphopenia-reversal observed in the Phase 2 QUILT-3.055 NSCLC study and other clinical programs.

In January 2026, we announced results from two studies in 151 patients spanning first-, second-, and later-line disease in NSCLC, showing that ANKTIVA demonstrated statistically significant immune restoration and a consistent association between lymphocyte recovery and improved survival in checkpoint-experienced patients.

• In second- and later-line patients, responders (defined as achievement or maintenance of an on-treatment ALC ≥ 1.0 × 10³/μL based on a mean on treatment ALC ≥ 1.0 × 10³/μL) experienced significantly longer overall survival compared with non-responders (median overall survival 16.2 vs 11.8 months;

hazard ratio 0.52;

p=0.0369), directly linking immune restoration to clinical benefit.

• Patients achieving higher immune competence (ALC ≥1.2 ×10³ cells/µL) demonstrated additional survival benefit, with median overall survival of 21.1 months (hazard ratio 0.33;

p=0.0009), independent of PD-L1 status, exceeding historical overall survival of 7-9 months with standard-of-care chemotherapy.

OUR CANCER BIOSHIELD PLATFORM

Our Cancer BioShield platform comprises multiple therapeutic modalities designed to activate both innate and adaptive immune responses:

Platform Components Addressing the Immune System

Platform Component Key Modalities

Cytokine Fusion Proteins

(Innate & Adaptive Immune System)

In vivo Activation of NK, Killer T and T memory cells:

ANKTIVA (IL-15 receptor superagonist fusion )

DNA and Vaccine Vectors

(Adaptive Immune System)

hAd5 vectors targeting:

– HPV [E6/E7]

– Neoantigens

– Nucleocapsid

NK Cell Therapies

(Innate Immune System)

CAR NK Platform:

– CD 19 CAR-NK (t-haNK)

– PD-L1 CAR-NK (t-haNK)

Apheresis Platform:

– M-ceNK (autologous and allogeneic)

Cytokine Fusion Proteins

Cytokine fusion proteins, such as ANKTIVA, represent a novel class of biologics that improve immune responses by enhancing the therapeutic potential of cytokines and promoting lymphocyte infiltration at a site of disease.

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells.

ANKTIVA is a first-in-class IL-15 receptor superagonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15Rα, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells.

The cytokine IL-15 plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells.

ANKTIVA is a first-in-class IL-15 receptor superagonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15Rα, which binds with high affinity to IL-15 receptors on

NK, CD4+, and CD8+ T cells.

This fusion complex of ANKTIVA, which confers stability and longer half-life than recombinant or native IL-15, mimics the natural biological properties of the membrane-bound IL-15Rα, delivering IL-15 by dendritic cells and drives the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones.

By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells without stimulating immunosuppressive T-reg cells and restores memory T cell activity with resultant prolonged duration of CR.

By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells without stimulating immunosuppressive Tregs and restores memory T cell activity with resultant prolonged duration of complete response.

Further, by stimulating the release of interferon-γ, ANKTIVA restores MHC-I expression, making more tumor cells targets for T cell killing.

As evidenced by its ability to increase lymphocyte counts in healthy adults in Phase 1 testing, ANKTIVA also has the potential to rescue lymphopenia, which is associated with poor prognosis in cancer before treatment or as a consequence of chemo or radiation therapy.

ANKTIVA’s mechanisms-of-action make it an ideal ‘backbone’ for combination therapy with the company’s platforms, such as second-generation hAd5 vaccines, off-the-shelf CAR-engineered NK cells, and M-ceNK cells, as well as other therapeutics including BCG, targeted antibodies, and CPIs.

Leveraging our success with ANKTIVA, we are developing multi-functional cytokine fusion proteins targeting TGF-ß, PD-L1, CD16, CD20, and comprising IL-12, IL-15, and IL-21, amongst others, to further enhance NK and T cell activation directed to the TME or virally infected cells and to modulate the systemic and local immune response to accelerate immunogenic cell death.

Leveraging ANKTIVA’s success, we are developing multi-functional cytokine fusion proteins targeting TGF-ß, PD-L1, CD16, CD20, and comprising IL-12, IL-15, and IL-21, amongst others, to further enhance NK and T cell activation directed to the tumor microenvironment or virally-infected cells and to modulate the systemic and local immune response to accelerate immunogenic cell death.

DNA and Vaccine Vectors

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These technologies can deliver DNA and protein subunits to induce B and T cell memory through activation of both CD4+ and CD8+ T cells along with antibody (humoral) responses.

Adenovirus is a well-established viral vector that can be utilized as a vaccine platform to stimulate the immune system, however there is risk for a treated person to develop adenovirus immunity.

Adenovirus is a well-established vector that can be utilized as a vaccine platform to stimulate the immune system, however there is risk for a treated person to develop anti-adenovirus immunity.

Our second generation hAd5 vector has unique deletions in the early 1 (E1), early 2 (E2b), and early 3 (E3) regions (hAd5 [E1-, E2b-, E3-]), which allows it to be effective in the presence of pre-existing adenovirus immunity and lowers the risk of generating de novo vector-directed immunity.

We have developed several hAd5 product candidates that have been evaluated in multiple clinical trials as potential vaccines for and treatments of certain cancers and infectious diseases.

We have developed several hAd5 candidates that have been evaluated in multiple clinical trials as potential vaccines for and treatments of certain cancers and infectious diseases.

Importantly, these product candidates have shown an ability to overcome previous adenovirus immunity in preclinical models and in cancer patients.

In oncology, we are clinically evaluating hAd5 product candidates in combination with ANKTIVA to yield immunological immunity in colon cancer (hAd5 TAAs CEA, MUC1, Brachyury;

In oncology, we are clinically evaluating hAd5 candidates in combination with ANKTIVA to yield immunological immunity in colon cancer (hAd5 TAAs CEA, MUC1, Brachyury;

collectively the TriAd) and prostate cancer (hAd5 PSA), and as a single agent in HPV-associated cancers (hAd5 TAA [E6/E7]).

Cell Therapies

We believe that we have one of the most comprehensive clinical-stage cell-based platforms in development.

Our engineered NK cells have demonstrated the ability to induce cell death in cancers and virally-infected cells through a variety of concurrent mechanisms including innate killing, antibody-mediated killing, and CAR-directed killing.

Table of Conten t s

Off-The-Shelf Targeted High-Affinity NK Cells

NK cells are a type of cytotoxic lymphocyte critical to the innate immune system.

NK cells show spontaneous cytolytic activity against cells under stress such as tumor cells and virally-infected cells.

After activation, NK cells secrete several cytokines such as interferon- γ (IFN-γ), tumor necrosis factor-α (TNF-α), granulocyte macrophage colony-stimulating factor (GM‑CSF), and chemokines that can modulate the function of other innate and adaptive immune cells.

Our proprietary NK-92 cytotoxic cell line (also referred to as aNK) was established from a patient with clonal NK-cell lymphoma.

aNK cells can be expanded in culture in the presence of cytokines (IL-2, IL-15).

Our “off-the-shelf” aNK cell platform has been molecularly engineered in a variety of ways to boost its killing capabilities against cancers and virally-infected cells.

Unlike normal NK cells, our aNK c ells do not express the key inhibitory receptors that diseased cells often exploit to turn off the killing function of NK cells thereby escaping elimination.

Further, w e have genetically engineered our aNK cell platform to generate haNK cells engineered to express the high-affinity variant of the Fc γ receptor ( Fc γRIIIA/CD16a 158V) as well as endoplasmic reticulum-retained IL-2 that bind to antibodies with demonstrated enhanced ADCC-mediated antitumor activity (Jochems 2016).

These antibody-targeted haNK cel ls are designed to directly bind to IgG1-type antibodies, such as avelumab, trastuzumab, cetuximab, and rituximab, with the intention of enhancing the cancer-killing efficacy of these antibodies by boosting the population of competent NK cells that can kill cancer cells through ADCC.

Our most advanced off-the-shelf NK cell platform, CAR-targeted t-haNK cells, enables innovative, bioengineered cell lines that incorporate all the features of our haNK platform together with a CAR, such as PD-L1.

Product candidates under this platform have three modes of killing:

innate, antibody-mediated, and CAR-directed killing.

These product candidates also include one or more additional expression elements such as functional cytokines, chemokines, and trafficking factors.

These product candidates are intended to be combined with commercially-available therapeutic antibodies to effectively target either two different epitopes of the same cancer-specific protein or two entirely different cancer-specific proteins.

A number of t-haNK cell lines that express CARs have been developed.

Findings from a preclinical study performed in collaboration with the NCI demonstrated our PD-L1 t-haNK cells exert potent antitumor effects against MDSC and overcome T cell escape in multiple types of resistant tumors.

The contribution of PD-L1 t‑haNK to antitumor efficacy is further evidenced by data reported at the ASCO meeting in June 2022 and updated at ASCO GI in January 2023 from the QUILT 88 trial of patients with advanced pancreatic cancer who were administered PD-L1 t-haNK, and ANKTIVA.

The multi-modal therapy resulted in a median overall survival of 6.3 months (95% CI:

5.0, 7.2 months) in patients who had progressed after two prior lines of therapy, more than doubling the historical survival rate.

haNK cells engineered with CARs targeting CD19 have shown to be effective against in vitro/in vivo models of lymphoblastic leukemia and lymphoma (Boissel 2013, Muller 2008, Romanski 2016).

The CD19 t-haNK cell line combines the engineered enhancements of haNK cells with the expression of a CAR targeting CD19 and thus has potential to demonstrate robust ADCC antitumor activity against cancerous B cells and provide clinical benefit to patients with R/R NHL.

Clinical trials to assess o ur t ‑ haNK product candidates have been initiated:

PD-L1 t-haNK in a Phase 1 trial in TNBC and a Phase 2 trial in pancreatic cancer;

and CD19 t-haNK in a Phase 1 trial in R/R B-Cell NHL.

In addition, the FDA recently granted us RMAT designation for ANKTIVA and PD-L1 t-haNK in combination with standard-of-care chemotherapy/radiotherapy indicated for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer.

Autologous and Allogeneic M-ceNK

We believe that our NK cell-based platforms are some of the most advanced at the clinical-stage of development in oncology.

NK cells are a type of cytotoxic lymphocyte critical to the innate immune system–they play a key role targeting tumor and virally-infected cells.

Activated NK cells secrete several key cytokines (IFN-γ, TNF-α, GM‑CSF) and chemokines that can modulate the function of other innate and adaptive immune cells.

Our NK platform works through innate, antibody-mediated, and CAR-directed killing mechanisms.

Off-The-Shelf Targeted CAR-NK Cells

Key attributes of our CAR-NK assets include:

• cytotoxicity and cytokine-directed cell expansion

• absence of key inhibitory receptors to maintain killing function

• ADCC-targeted killing through high-affinity CD16 (Jochems 2016) – allowing engagement with IgG1-type antibodies (e.g., BAVENCIO ® , trastuzumab, etc.)

• CAR receptors such as PD-L1 and CD-19

◦ PD-L1 CAR-NK (PD-L1 t-haNK):

potent antitumor effects against MDSCs and overcome T cell escape in multiple types of resistant tumors.

◦ CD19 CAR-NK (CD19 t-haNK):

robust ADCC antitumor activity against cancerous B cells and with potential applications for patients with r/r NHL.

Our clinical programs including our CAR-NK product candidates have been initiated with promising early readouts in a range of oncology indications:

• PD-L1 CAR-NK

◦ TNBC (Phase 1)

◦ Pancreatic cancer QUILT-88 (Phase 2)

◦ GBM QUILT-3.078 (Phase 2)

• CD19 t-haNK (Phase 1 trials)

◦ r/r NHL QUILT-3.092

◦ r/r selected CD19+ and CD20+ NHL QUILT-106

ANKTIVA + PD-L1 CAR-NK (t-haNK) has received FDA RMAT designation for use in combination with standard-of-care chemotherapy/radiotherapy for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer.

Autologous and Allogeneic M-ceNK (World Bank of Natural Killer Cells)

NK persistence and function can be enhanced with cytokine stimulation.

Our M-ceNK cells are generated from lymphocytes collected from donors that are then pre-activated ex-vivo by exposure to interleukins -12 (IL-12), -15 (N-803) and -18 (IL-18), which results in differentiation and acquisition of enhanced responses to cytokine re-stimulation.

The apheresis processing and cell manufacturing activities for these studies are currently performed by trained personnel using controlled, manual processes designed to ensure product quality and consistency.

M-ceNK have increased antitumor characteristics, including enhanced IFN-γ production and cytotoxicity against leukemic cell lines.

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Also, we can manufacture these cell products for clinical delivery using our proprietary methods and overall expertise in scale manufacturing of NK cell-based products.

A Phase 1 first-in-human trial is open and actively enrolling patients to study the M-ceNK platform in solid tumors (QUILT 3076).

In addition, M-ceNK is being evaluated in combination with ANKTIVA and gemcitabine in patients with recurrent platinum-resistant high-grade ovarian cancer (ResQ209) and in combination with ANKTIVA and hAd5-PSA in high-risk prostate cancer (ResQ110A-B).

Table of Conten t s

Indications (Current Prioritized Studies)

We have initiated or completed a series of trials evaluating the safety and feasibility of the technology including:

• NK2022 & NK2023 (Cancer Patients & Healthy Donors):

64 subjects completed apheresis and M-ceNK manufacturing cell therapy process development for robotic training and future AI robot manufacturing.

Cells cryopreserved and stored.

• QUILT-3.076:

Safety Phase 1 of apheresis and M-ceNK and ANKTIVA completed:

Solid tumor trial with apheresis followed by M-ceNK and ANKTIVA that enrolled 10 patients treated with autologous M-ceNK infusion

• QUILT-105 (Healthy Volunteers):

Apheresis followed by ANKTIVA stimulation prior to second apheresis

We believe our studies have demonstrated that M-ceNK cells can be reliably manufactured, cryopreserved, and administered with acceptable safety and tolerability profiles and evidence of immune activation, supporting continued clinical development.

We continue to improve the workflow and manufacturing techniques and intend to incorporate increased artificial intelligence and fully robotic automation over time to support scalability in our cellular therapies as the program advances.

Platform Components Addressing the Immune System

As of December 31, 2025, key elements of our pipeline include clinical-stage programs in the following indications:

• Bladder Cancer:

In the U.S., bladder cancer was the sixth most commonly-diagnosed cancer and the fourth most commonly-diagnosed solid malignancy in men in 2024.

The American Cancer Society estimates there will be 84,870 new cases and 17,420 deaths from bladder cancer in 2025.

BCG-unresponsive NMIBC CIS with or without papillary tumors (approved), BCG-unresponsive papillary, BCG-naïve NMIBC

• Lung Cancer:

Progressing, metastatic NSCLC in combination with CPIs (conditional approval in Saudi Arabia)

• Lymphopenia:

Tumor-agnostic treatment of chemotherapy/radiation-induced lymphopenia (EAP authorized)

• Pancreatic Cancer:

Advanced/metastatic disease (RMAT designation)

• Glioblastoma:

Recurrent GBM (registration trial)

• Non-Hodgkin Lymphoma:

Waldenström macroglobulinemia and other CD19+/CD20+ lymphomas

• Colorectal Cancer/Lynch Syndrome:

Cancer prevention in high-risk patients (NCI-sponsored)

• Prostate Cancer:

High-risk prostate cancer

• Ovarian Cancer:

Platinum-resistant ovarian cancer

• Infectious Diseases:

HIV, Long COVID, universal nucleocapsid vaccine

• Apheresis Platform:

M-ceNK with cryopreservation and storage

PIPELINE SUMMARY

Product Candidate Indication Phase Status

ANKTIVA + BCG BCG-unresponsive NMIBC CIS Approved FDA, MHRA and SFDA approval;

EU (EMA) conditional marketing authorization

ANKTIVA + CPI Progressing, metastatic NSCLC Approved/Phase 3 SFDA conditional approval

ANKTIVA + BCG BCG-naïve NMIBC Phase 2B 85% enrolled

ANKTIVA + BCG BCG-unresponsive papillary sBLA Resubmission plan

ANKTIVA + PD-L1 CAR-NK Recurrent GBM Phase 2/3 Registration trial

ANKTIVA + PD-L1 CAR-NK Pancreatic cancer Phase 2 RMAT designation

CD19 CAR-NK + rituximab NHL Phase 1 QUILT-106

ANKTIVA Lymphopenia (solid tumors) Expanded Access FDA EAP authorized

rBCG (Serum Institute) NMIBC Expanded Access FDA EAP authorized

M-ceNK Solid tumors Phase 1 Completed

Ad-HPV HPV Phase 2 Initiated and enrolling

CLINICAL DEVELOPMENT PROGRAMS

Bladder Cancer

According to the American Cancer Society, bladder cancer is the sixth most diagnosed cancer in the U.S., with an estimated 84,530 new cases and 17,870 deaths expected in 2026.

NMIBC represents approximately 75% of all bladder cancers.

Radical cystectomy is a treatment to control the disease for unresponsive NMIBC;

however, the procedure introduces compromise to the quality of life and additional costs.

There is an urgent, unmet need to treat NMIBC and avoid radical cystectomy of the bladder in an attempt to control the disease.

ANKTIVA received Breakthrough Therapy and Fast Track designations from the FDA for the treatment of BCG-unresponsive NMIBC with CIS (Cohort A) with or without papillary tumors for which we received approval from the FDA in April 2024.

ANKTIVA also received Fast Track designation for BCG-unresponsive NMIBC papillary and BCG-naïve NMIBC with CIS.

The receipt of such designations may not lead to a faster development process or regulatory review and may not increase the likelihood that our product candidates will receive marketing approval.

In our QUILT 3032 trial, as we reported in November 2022 in NEJM Evidence , the primary end points were met for both BCG-unresponsive NMIBC with CIS with a CR rate of 71%, and BCG-unresponsive NMIBC papillary with a 12-month disease-free rate of 55%.

As presented at ASCO 2022, the combination of BCG plus ANKTIVA (as measured in BCG-unresponsive NMIBC patients, Cohorts A and B combined) was well-tolerated with 1% treatment-related serious adverse events, 0% immune-related serious adverse events, and 100% bladder cancer-specific overall survival at 24 months.

Low-grade treatment-related adverse events include dysuria (22%), pollakiuria (20%), hematuria (17%), fatigue (16%), and urgency (12%), and all other treatment-related adverse events were seen at 7% or less.

Seminal patents covering intravesical administration of BCG and ANKTIVA were issued providing term coverage until 2035.

BCG-Unresponsive NMIBC with CIS (Cohort A) – QUILT 3032

In our Phase 2/3 open-label multi-center trial of BCG-unresponsive high-grade NMIBC patients with CIS, the patients receive BCG plus ANKTIVA weekly for six consecutive weeks during induction.

The patients also receive additional treatment including three weekly maintenance instillations every three months for up to 12 months and then at month 18.

Patients with no disease or low-grade Ta disease at months 24, 30, and 36 are eligible for continued BCG plus ANKTIVA (Cohort A) or ANKTIVA alone (Cohort C) treatment (3 weekly instillations), at the principal investigators’ discretion.

The primary endpoint of the BCG-unresponsive NMIBC with CIS trial is a CR rate at any time equal to or greater than 30% and the lower bound of the 95% CI must be greater than or equal to 20% for success.

CR, or the disappearance of measurable disease in response to treatment, is evaluated at three months or six months following initial administration of BCG plus ANKTIVA (and every three months thereafter until 24 months).

This endpoint would be achieved once at least 24 of the 80 patients in the trial achieve a CR.

A data cut-off occurred in January 2022, which provided a median follow-up in Cohort A of approximately 24 months.

Data published in NEJM Evidence in November 2022 showed a CR in 58 of 82 patients with a 71% CR rate (95% CI:

59.6, 80.3) and a median duration of CR of 26.6 months (95% CI:

Radical cystectomy is a treatment option for unresponsive NMIBC;

however, the procedure significantly impacts quality of life.

Regulatory Designations:

Breakthrough Therapy (BCG-unresponsive NMIBC CIS with or without papillary tumors);

Fast Track (BCG-unresponsive NMIBC with papillary tumors, BCG-naive NMIBC with CIS).

Seminal patents covering intravesical administration of BCG and ANKTIVA have been issued with term coverage until 2035.

BCG-Unresponsive NMIBC CIS (Cohort A) QUILT-3.032

Trial Design:

Phase 2/3 open-label multi-center trial.

Patients received BCG with ANKTIVA weekly for six consecutive weeks during induction, followed by three weekly maintenance instillations at three-month intervals for up to 12 months and then at month 18.

Patients with no disease or low-grade Ta disease at months 24, 30, and 36 were eligible for continued BCG with ANKTIVA treatment (3 weekly instillations), at the principal investigators’ discretion.

Primary Endpoint:

Complete response rate at any time of 30% or greater with a lower bound of 95% CI of 20% or greater.

Complete response, or the disappearance of measurable disease in response to treatment, is evaluated at three months or six months following initial administration of BCG plus ANKTIVA (and every three months thereafter until 24 months).

This endpoint would be achieved once at least 24 of the 80 patients in the trial achieve a complete response.

Results (published in NEJM Evidence, November 2022):

• Complete Response Rate:

71% (58 of 82 patients;

59.6%, 80.3%)

• Median Duration of Complete Response:

26.6 months (95% CI:

9.9, upper bound not reached)

At 24 months in patients with a CR, the probability of avoiding cystectomy and disease-specific survival was 91.4% and 100%, respectively.

Also, at 24 months in all patients in Cohort A, the probability of avoiding cystectomy and of disease-specific survival was 84.1% and 100%, respectively.

In December 2024, we provided an update on the full enrollment of 100 patients with BCG-unresponsive NMIBC with CIS as of November 2024 that have been treated with ANKTIVA in combination with BCG, with a 71% CR rate.

In these responders, the range of durable response extended to 54 months.

This data was submitted to the EMA in an MAA for ANKTIVA in the EU in December 2024.

As part of planned analyses, BCG-unresponsive patients in the QUILT 3032 trial of ANKTIVA plus BCG completed PRO questionnaires, which revealed stability of both mean physical function and global health from baseline to 24 months on-study for those participants who had reached the 24-month assessment.

Further, at month 6, Cohort A (CIS disease) patients that achieved a CR reported higher physical function scores than those without a CR (P=0.0659).

Summary scores for the NMIBC-specific questionnaire also remained stable.

These PROs, taken together with efficacy findings from both the NEJM Evidence report and subsequent follow-up, suggest a favorable risk-benefit ratio for the novel therapeutic combination.

Table of Conten t s

In May 2022, we submitted a BLA to the FDA for our product candidate, ANKTIVA in combination with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors.

In May 2023, we received a CRL from the FDA, indicating that the FDA had determined it could not approve the original BLA submission in its initial form, citing deficiencies related to the FDA’s pre-license inspection of our third-party CMOs, among other items and made recommendations to address the issues raised.

The CRL that we received in response to our initial BLA submission required us to resubmit the BLA to the FDA addressing the issues in the CRL.

On April 22, 2024, the FDA approved our product, ANKTIVA with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors.

• 24-Month Cystectomy Avoidance:

91.4% in patients with complete response;

84.1% in all patients

• 24-Month Disease-Specific Survival:

1% treatment-related serious adverse events;

0% immune-related serious adverse events

Updated Results (December 2024):

Full enrollment of 100 patients completed.

Complete response rate of 71% maintained.

Durable responses extending to 54 months.

This data supported the EMA’s conditional marketing authorization that was granted in February 2026.

Regulatory Status:

In April 2024, the FDA approved ANKTIVA with BCG for the treatment of adult patients with BCG-unresponsive NMIBC CIS with or without papillary tumors (after we had resubmitted our BLA in May 2023 after an initial CRL related to deficiencies associated with the FDA’s pre-license inspection of our third-party CMOs, among others).

In July 2025, ANKTIVA received approval from the MHRA for the UK and in January 2026 received accelerated approval from the SFDA in Saudi Arabia in the same indication.

In February 2026, the European Commission granted conditional marketing authorization in the EU for ANKTIVA in combination with BCG for adult patients with BCG-unresponsive NMIBC CIS with or without papillary tumors.

We are required to comply with certain post-marketing commitments, including completion of our QUILT-3.032 clinical trial and annual reporting for up to four years, with a final report submission to the FDA by the end of 2029.

We began commercial distribution of our approved product in May 2024.

BCG-Unresponsive NMIBC Papillary (Cohort B) – QUILT 3032

In our Phase 2, open-label multi-center trial of BCG-unresponsive high-grade NMIBC papillary patients (Cohort B), the patients are receiving BCG plus ANKTIVA weekly for six consecutive weeks during induction.

BCG-Unresponsive NMIBC With Papillary Tumors (Cohort B), QUILT-3.032

Trial Design:

Phase 2 open-label multi-center trial.

Patients received BCG plus ANKTIVA weekly for six consecutive weeks during induction.

The patients also receive additional treatment including three weekly maintenance instillations every three months for up to 12 months and then every nine months for up to 24 months

The primary endpoint of the trial is a 12-month disease free rate greater than or equal to 30% and the lower bound of the 95% CI must be greater than or equal to 20% for success.

Primary Endpoint:

12-month disease-free survival rate greater than or equal to 30% and the lower bound of the 95% CI must be greater than or equal to 20% for success.

To meet the primary endpoint, 24 out of 80 patients must be disease free at 12 months.

A data cut-off occurred in January 2022, which provided a median follow-up in Cohort B of approximately 21 months.

Data published in NEJM Evidence in November 2022 showed a 12-month disease-free survival rate of 55% (95% CI:

42.0, 66.8), with median disease-free survival of 19.3 months (95% CI:

7.4, [upper bound not reached]).

At the cutoff date 67 of 72 patients, 93.1%, had not progressed to radical cystectomy and the 24-month disease-free survival rate was 97.7%.

We are preparing to submit an sBLA in 2025 for our innovative treatment targeting BCG-unresponsive NMIBC in the papillary indication.

This immunotherapy of rescuing BCG with ANKTIVA represents a step towards providing therapeutic options in patients with BCG unresponsive NMIBC in papillary disease who currently have limited treatment choices and face radical total cystectomy (removal of bladder).

The addition of the BCG-unresponsive NMIBC papillary indication could expand the potential patient population benefiting from this therapy and may allow patients to avoid the high morbidity and mortality associated with radical total cystectomy.

BCG-N aïve NMIBC with CIS – QUILT 2005

Results (published in The Journal of Urology, Chang et al., January 2026):

• 12-Month Disease-Free Survival:

58.2% (95% CI:

46.6%, 68.2%)

• 36-Month Disease-Specific Survival:

96.0% (median not reached)

• 36-Month Progression-Free Survival:

• 12-Month Cystectomy-Free Survival:

• 36-Month Cystectomy-Free Survival:

Regulatory Status:

At a Type B meeting in December 2025, the company presented an overview of the clinical status of its papillary disease program, including more than five years of follow-up data supporting the papillary indication.

Based on these discussions, the FDA recommended the company provide certain additional information for its consideration to support a potential filing and review of the sBLA initially submitted in 2025 for the papillary indication.

The company submitted the requested information to the Agency in February 2026.

There can be no assurance that we will be successful in our efforts to resolve the May 2025 RTF letter with the FDA and/or that our sBLA, or any newly submitted sBLA or BLA, will be accepted for filing and review in this indication in a timely manner, or at all, without the need to conduct a new RCT prior to submission, or that we will ultimately receive approval even if it is accepted for filing.

As presented at ASCO 2022, the combination of BCG plus ANKTIVA (as measured in BCG-unresponsive NMIBC patients, Cohorts A and B combined from QUILT-3.032) was well-tolerated with 1% treatment-related serious adverse events, 0% immune-related serious adverse events, and 100% bladder cancer-specific overall survival at 24 months.

BCG-Naïve NMIBC with CIS, QUILT-2.005

As discussed above, ANKTIVA received Fast Track designation from the FDA for the treatment of BCG-naïve NMIBC with CIS.

We are currently enrolling patients in our Phase 2b blinded, randomized, two-cohort, open-label, multi-center trial of intravesical BCG plus ANKTIVA vs.

BCG alone, in BCG-naïve patients with high-grade NMIBC with CIS (Cohort A) and NMIBC papillary (Cohort B ).

Planned enrollment for Cohort A (CIS) and Cohort B (papillary) is 366 patients and 230 patients, respectively.

As part of our BLA resubmission for ANKTIVA in combination with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors, we provided an update on the long-term follow-up of BCG-naïve patients in QUILT 2005 receiving ANKTIVA plus BCG for CIS± Ta/T1 in the Phase 1b trial, examining the survival of the 9 subjects who entered the trial since 2014.

As initially reported in 2021, all 9 patients (100%) achieved a CR, and in an 8-year follow up, the 6 evaluable patients remain disease-free (two were deceased from causes other than bladder cancer and one was lost to follow-up) with bladder preservation over a median survival period of 8.8 years.

As part of our Breakthrough Therapy designation submission for BCG-unresponsive NMIBC with CIS with or without papillary tumors described above, the FDA requested an interim analysis of 43 patients in our QUILT 2005 trial which showed an 84% CR rate at nine months in patients receiving ANKTIVA plus BCG.

We continue to enroll patients and expect full enrollment in late 2025 to early 2026 with a data readout from the pivotal clinical trial in the second half of 2026.

We are targeting a BLA submission to the FDA in late 2026 to early 2027.

Table of Conten t s

NMIBC – Recombinant BCG as Alternative Source of BCG

In May 2024, we announced an exclusive global arrangement with Serum Institute, the world’s largest manufacturer of vaccines by number of doses produced, to supply ImmunityBio with rBCG for use exclusively in combination with ANKTIVA, subject to regulatory approvals.

We are responsible, in part, for regulatory submissions, clinical trials and commercialization efforts, and our exclusive rights under the arrangement extend to the scope of the FDA’s approval obtained by us for Serum Institute’s rBCG product in the U.S.

In February 2025, the FDA authorized an EAP allowing us to provide rBCG developed by Serum Institute to urologists to address the TICE BCG shortage in all settings where the TICE BCG label is approved, and shipments of rBCG pursuant to the EAP are expected to begin during the first quarter of 2025.

In addition, we are testing rBCG in an FDA-approved clinical trial (ResQ133A) of intravesical rBCG in participants with NMIBC eligible to receive TICE BCG.

According to the American Cancer Society, lung cancer is the second most common cancer in the U.S.

In 2025, it is estimated that 226,650 new cases of lung cancer will be diagnosed in the U.S.

and 124,730 deaths will be attributed to the disease.

NSCLC accounts for about 87% of all lung cancer diagnoses and there are very few successful treatment options for these patients once the cancer spreads beyond the lungs.

The development of CPIs in NSCLC has been revolutionary, doubling the median overall survival in some settings;

however, patient response may be short lived, due to late response and/or disease progression after achieving an initial response.

As with bladder cancer, ANKTIVA enhances the proliferation and activation of NK and T cells critical for targeting and killing lung cancer cells.

There is therefore a strong rationale to evaluate ANKTIVA in addition to a PD-1 or PD-L1 CPI for patients with NSCLC who have relapsed after achieving an initial response to PD-1 or PD-L1 CPI therapy.

Analysis of pooled data from a Phase 1/2 trial conducted from January 2016 to June 2017 in 23 patients and a subsequent investigator-initiated Phase 2 trial conducted by the Medical University of South Carolina, yielded confirmation of activity of the combination of CPIs and ANKTIVA in relapsed NSCLC relative to historical response rates.

In 15 patients with PD-L1 greater than 50%, the overall response rate was 38% and the median overall survival rate was 17.1 months.

These preliminary findings were favorable relative to the historical response rates seen in this patient population in the first-line setting with CPI therapy.

Non-Small Cell Lung Cancer – QUILT 3055

On the basis of these findings discussed above, we initiated a single-arm Phase 2b multi-cohort basket trial of ANKTIVA and CPI combinations in patients who have previously received treatment with PD-1/PD-L1 immune CPIs per an FDA-approved indication.

Patients enrolled in this trial were eligible if actively progressing on CPI therapy.

Upon enrollment, patients continued on the same CPI but with the addition of ANKTIVA.

Despite progressing on CPI therapy upon entry into the trial, the majority of patients reverted to stable disease and demonstrated durability of stable disease, some extending as long as nine months.

Data presented at the ASCO Annual Meeting in 2021 showed that despite the patients’ prior progression on CPI therapy alone, upon entry into the trial the majority of patients experienced clinical benefit either as stable disease (49%) or a partial response (9%).

Trial Design:

Phase 2B blinded, randomized, two-cohort trial of intravesical BCG plus ANKTIVA versus BCG alone in BCG-naive patients with high-grade NMIBC.

Cohort A (CIS):

366 patients planned;

Cohort B (papillary):

230 patients planned.

As of January 2026, enrollment is 85% complete in Cohort A, with full enrollment expected in Q2 2026.

Historical Data (Phase 1B, N=9 since 2014):

100% complete response rate.

8-year follow-up:

all 6 evaluable patients remain disease-free with bladder preservation over a median survival period of 8.8 years.

Interim Analysis (FDA-requested, N=43):

84% complete response rate at nine months.

Statistically significant longer duration of complete response with ANKTIVA in combination with BCG compared to BCG alone.

Pivotal data readout expected in the second half of 2026.

BLA submission target set for late 2026 to early 2027.

Recombinant BCG Supply Solution

In May 2024, we announced an exclusive global arrangement with Serum Institute to supply us with rBCG for use in combination with ANKTIVA.

This addresses a significant supply challenge:

TICE BCG (Merck) has been the sole supplier of BCG product in the U.S.

since 2012, and rationing has been ongoing since 2019.

According to published surveys, 57% of U.S.

urologists report being unable to treat patients due to the BCG shortage, affecting an estimated 35,000 patients annually.

Regulatory Progress:

In February 2025, the FDA authorized an EAP for rBCG.

In Q1 2025, shipments commenced under the EAP.

The company continues to work with the FDA to solve this 13-year shortage.

According to the American Cancer Society, lung cancer is the second most common cancer in the U.S., with an estimated 229,410 new cases and 124,990 deaths in 2026.

NSCLC accounts for approximately 83% of all lung cancer diagnoses.

Second-Line and Beyond NSCLC

Trial Design:

Single-arm Phase 2B multi-cohort basket trial of ANKTIVA and CPI combinations in patients who were actively progressing on prior PD-1/PD-L1 CPI therapy.

Results (presented at IASLC World Conference on Lung Cancer, September 2024 and January 2026):

• Patients enrolled:

86 evaluable patients in pooled analysis

• Median overall survival:

14.1 months (95% CI:

• Published Historical Comparator (any therapy post-CPI, Freeman et al., 2020):

• Published Historical Comparator (docetaxel + CYRAMZA, Brueckl et al., 2021):

• Maximum overall survival:

• Patients achieving ALC >=1.2 x 10³ cells/µL:

• Median overall survival in patients with ALC >=1.2 x 10³ cells/µL :

15.8 months (95% CI:

• Median overall survival in patients with ALC <1.2 :

11.5 months (95% CI:

Among 147 patients enrolled in QUILT-3.055, the common ANKTIVA attributed grade 1 and 2 adverse events included:

injection-site reaction (71%), chills (34%), fatigue (27%), pyrexia (24%), flu-like illness (13%), and decreased appetite (10%).

A total of 18 grade 3 and 4 adverse events attributed to ANKTIVA have been reported among 16 patients (12%) in the trial as of February 2021.

All reported grade 3 and 4 adverse events occurred at a frequency of 5% or less;

two patients reported increased alanine amino transferase, increased aspartate amino transferase or increased blood alkaline phosphatase, anemia, injection-site reaction, or injection-site pain.

All other occurrences of grade 3 or 4 adverse events that the clinical trial site investigators reported as suspected as being due to ANKTIVA include:

decreased lymphocyte count;

influenza-like illness;

injection-site pruritus;

injection-site cellulitis;

deep vein thrombosis;

hypovolemic shock;

respiratory failure;

and maculopapular rash.

Based on this relatively well-tolerated adverse event profile, coupled with NK and CD8+ T cell stimulatory effects, we believe that ANKTIVA has the potential to become a standard in combination with other immunotherapies for multiple indications.

Table of Conten t s

In September 2024, Dr.

John Wrangle gave an oral presentation of the updated QUILT 3055 NSCLC pooled data at the World Conference on Lung Cancer, with data through February 2024 from several cohorts of NSCLC patients who have progressed after CPI therapy.

These cohorts are:

• Cohort 1a – NSCLC patients with initial response on single-agent CPI therapy and subsequently progressed on or after that therapy.

• Cohort 2 – NSCLC patients having high PD-L1 expression (tumor proportion score ≥50%) and disease progression on a PD-1/PD-L1 CPI after experiencing an initial response when received CPI as a single-agent for first-line treatment.

• Cohort 3 – NSCLC patients with initial response but subsequently relapsed on maintenance PD-1/PD-L1 CPI therapy when initially received CPI therapy in combination with chemotherapy as first-line treatment.

• Cohort 4 – NSCLC patients currently receiving PD-1/PD-L1 CPI therapy that progressed after experiencing stable disease for at least 6 months during previous treatment with PD-1/PD-L1 CPI therapy.

These results showed a median overall survival of 14.1 months in the 86 patients in the pooled analysis.

This is in contrast to the overall survival of 6.1 months (Freeman et al.

2020) for patients who received any therapy post-CPI therapy progression or an overall survival of 7.5 months (Brueckl et al.

2021) for patients who received docetaxel plus ramucirumab after initial failure of first-line chemotherapy plus a CPI.

The Phase 2b study demonstrated prolonged overall survival when ANKTIVA was combined with the same CPIs on which patients were progressing, validating the rescue potential of ANKTIVA for T cells and CPIs.

The combination of ANKTIVA plus a CPI represents an immunotherapeutic advance for this disease, when compared to the most frequently used chemotherapy docetaxel in this setting, which has an overall survival ranging from 7 to 10 months and which is associated with high toxicities as a chemotherapeutic agent.

Overall survival in checkpoint relapsed patients ranged up to 58 months.

The long duration of survival is potentially a result of ANKTIVA’s mechanism of action to stimulate and proliferate memory T cells and overcome immune exhaustion or immune escape mediated by MHC-loss in checkpoint relapse via stimulation of NK cells.

We plan to submit a BLA in 2025 for second-line and third-line treatment of patients with NSCLC, who are progressing on CPIs.

Non-Small Cell Lung Cancer – ResQ201A

Following a meeting with the FDA, we launched a pivotal, randomized, open-label Phase 3 clinical trial of ANKTIVA plus tislelizumab (anti-PD-1) and docetaxel vs.

docetaxel monotherapy in participants with advanced or metastatic NSCLC who have acquired resistance to immune CPI therapy.

A total of 462 patients will be enrolled 1:2 either in a control arm or an experimental arm.

• Control arm:

Docetaxel (standard of care) N=154.

Repeated 3-week cycles with docetaxel.

• Experimental arm:

ANKTIVA, tislelizumab, N=308.

Two 3-week cycles of ANKTIVA, tislelizumab plus docetaxel followed by repeated 3-week cycles of ANKTIVA and tislelizumab (no docetaxel).

Participant randomization to either the control or experimental arm will be stratified by geographical region (North America vs.

injection-site reaction (84%), chills (44%), fatigue (30%), pyrexia (28%), nausea (16%), injection site erythema (14%), injection site pruritus (14%), injection site pain (12%), influenza like illness (12%), and decreased appetite (10%).

A total of 38 grade 3 or higher adverse events attributed to ANKTIVA have been reported among 24 patients (16%) in the trial as of January 2026.

All reported grade 3 or higher adverse events occurred at a frequency of 2% or less including:

fatigue, injection site reaction, chills, injection site pain, injection site illness, injection site erythema, injection site pruritus, aspartate aminotransferase increased, alanine aminotransferase increased, blood alkaline phosphatase increased, lymphocyte count decreased, weight decreased, anaemia, diarrhoea, colitis, ileus, small intestinal obstruction, pneumonitis, respiratory failure, rash maculo-papular, deep vein thrombosis, hypovolaemic shock, pericardial effusion, tricuspid valve incompetence, and injection site cellulitis.

First-Line NSCLC

Trial Design:

Randomized Phase 3 trial to evaluate ANKTIVA in combination with CPIs versus other CPI combinations in the first-line setting for NSCLC

• Immunotherapy (ANKTIVA + KEYTRUDA ® vs.

KEYTRUDA) for either squamous or non-squamous NSCLC with PD-L1 TPS >1% (Cohort A)

• Chemoimmunotherapy (ANKTIVA with Carboplatin, Abraxane and KEYTRUDA versus Carboplatin, Abraxane / paclitaxel and KEYTRUDA) for squamous NSCLC (Cohort B)

• Chemoimmunotherapy (ANKTIVA with Cisplatin / Carboplatin, KEYTRUDA and Pemetrexed versus Cisplatin / Carboplatin, KEYTRUDA and Pemetrexed) for non-squamous NSCLC (Cohort C)

Key Results (January 2026):

ANKTIVA in combination with a CPI demonstrated statistically significant immune restoration across 151 patients with NSCLC:

• Randomized comparison demonstrated statistically significant and sustained increase in ALC with ANKTIVA in combination with a CPI versus CPI alone (p=0.0065)

• Responders (ALC restoration >=1.0 x 10³ cells/µL) achieved in 77% of patients

• Responders had significantly longer OS:

median 16.2 vs 11.8 months (hazard ratio 0.52;

• Patients achieving ALC >=1.2 x 10³ cells/µL:

median OS 21.1 months (hazard ratio 0.33;

• Results independent of PD-L1 status

Regulatory Status:

In January 2026, the SFDA granted conditional approval of ANKTIVA for use in combination with immune CPIs for the treatment of adult patients with metastatic NSCLC whose disease has progressed following standard-of-care therapy.

This followed review of the clinical data from QUILT-3.055 in second-line and greater NSCLC patients and from QUILT-2.023 in first-line NSCLC patients which demonstrated significant immune restoration and a consistent association between lymphocyte recovery with improved survival in checkpoint-experienced patients.

During 2026, we plan submissions for the expansion of the label in the MENA region for multiple tumor types.

Phase 3 Confirmatory Trial

Trial Design:

Pivotal, randomized, open-label Phase 3 trial comparing ANKTIVA in combination with TEVIMBRA ® (anti-PD-1) and docetaxel versus docetaxel monotherapy in participants with advanced or metastatic NSCLC who have acquired resistance to CPI therapy.

Primary Endpoint:

Comparison of overall survival between the experimental and the control arms.

462 patients randomized 2:1.

Experimental arm (N=308):

ANKTIVA in combination with TEVIMBRA.

Control arm (N=154):

Participant randomization to either the experimental or control arm will be stratified by geographical region (North America vs.

Asia), NSCLC histology (squamous vs.

nonsquamous), and actionable genomic alterations.

The primary outcome is the comparison of overall survival between the experimental and the control arms.

We expect full enrollment in early 2026 and a data readout in the second half of 2027.

Colorectal Cancer

According to the American Cancer Society, colorectal cancer is the third-leading cause of cancer-related deaths in the U.S.

in men and the fourth-leading cause in women, but it is the second most common cause of cancer deaths when numbers for men and women are combined.

Colorectal cancer is expected to cause about 52,900 deaths during 2025.

Table of Conten t s

Lynch Syndrome – QUILT 5015 (NCI)

Lynch Syndrome is the most common cause of hereditary colorectal cancer.

People with this syndrome harbor mutations in mismatch repair genes that put them at high risk of developing colorectal cancer.

Lynch Syndrome causes about 4,300 c olorectal cancers per year.

These cancers are more likely to develop at earlier ages, often before the age of 50.

If someone has Lynch Syndrome, it means that their close relatives (parents, siblings, and children) have a 50% chance of having the mutation that causes it too.

A Phase 2 trial sponsored by the NCI evaluates the ability of ANKTIVA in combination with our TriAd5–a combination of three vaccines targeting TAAs CEA, MUC1, and Brachyury– to reduce the incidence of cancer onset in people with Lynch Syndrome.

The trial recently reached full accrual of participants in the first two open-label phases.

The randomized controlled portion of the trial is now recruiting with plans to enroll up to 138 participants.

Pancreatic Cancer

According to the American Cancer Society, pancreatic cancer is the third-leading cause of cancer-related deaths in the U.S.

in men and the fourth-leading cause in women, and is also the third most common cause of cancer deaths when numbers for men and women are combined.

Pancreatic cancer is expected to cause about 52,000 deaths during 2025, with a five-year survival rate for late-stage cases of only 3%.

January 2025 collaboration with BeOne.

Full enrollment expected in the first half of 2027.

We continue to explore our strategy for potential accelerated approval in NSCLC including potential submissions to multiple regulatory authorities (Ex-U.S.) for accelerated approval in 2026 as described above.

Discussions are also planned to be requested with the U.S.

FDA in 2026 for an accelerated approval pathway based on new data from combined QUILT-2.023 (randomized) and QUILT-3.055 (single arm) trials.

Lymphopenia and Solid Tumors

Based on published literature and internal estimates, lymphopenia affects a substantial number of U.S.

cancer patients.

According to the American Cancer Society, an estimated 2,114,850 new cancer cases will be diagnosed in the U.S.

Approximately 90% of cancer patients have solid tumors, and lymphopenia is commonly observed following standard treatments, including chemotherapy, radiation therapy, and certain immunotherapies.

Clinical Evidence for Lymphopenia Reversal

QUILT-88 Pancreatic Cancer Data (presented at ASCO 2025, Abstracts #8054 Satoskar et al., and #2663 Saleh et al.):

In 86 participants with third-to-sixth-line metastatic pancreatic cancer with high tumor burden (CA19-9 levels exceeding 34,000 IU/mL):

• Lymphopenia Reversal (ALC >=1,000):

Achieved in 67/86 subjects (78%)

• Survival Correlation:

Subjects with lymphopenia reversal had significantly prolonged median overall survival versus those remaining in severe lymphopenia (p=0.005;

hazard ratio 0.46;

• With Lymphopenia Rescue plus Lower Tumor Burden (CA19-9 <34,000 IU/mL):

median overall survival exceeded 10 months

QUILT-3.055 and QUILT-2.023 NSCLC Data:

Across 151 patients spanning first-, second-, and later-line disease:

• In first-line a statistically significant and sustained increase in ALC from baseline with ANKTIVA plus CPI compared with CPI alone (p=0.0065

• In second- and later-line demonstrated restoration or maintenance of ALC ≥1.0 × 10³ cells/µL in 77% of patients receiving ANKTIVA plus CPI (responders)

• Responders receiving ANKTIVA plus CPI experienced significantly longer overall survival compared with non-responders (median OS 16.2 vs 11.8 months;

hazard ratio 0.52;

p=0.0369), directly linking immune restoration to clinical benefit

• ALC ≥1.2 ×10³ cells/µL demonstrated additional survival benefit, with median OS of 21.1 months (hazard ratio 0.33;

p=0.0009), independent of PD-L1 status, exceeding historical overall survival of 7-9 months with standard-of-care chemotherapy

• Regulatory Designations for Lymphopenia

RMAT Designation (February 2025):

FDA granted Regenerative Medicine Advanced Therapy designation for ANKTIVA and PD-L1 CAR-NK (t-haNK) in combination with standard-of-care chemotherapy/radiotherapy for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer.

Expanded Access Program (June 2025):

The FDA granted EAP authorization for our Cancer BioShield platform, anchored by ANKTIVA, to treat lymphopenia in adult patients with refractory or relapsed solid tumors, regardless of tumor type, who have progressed after first-line standard-of-care treatment.

The EAP includes patients with ALC <1,000/μL.

Lymphopenia Strategy

Sepsis is a serious condition and a leading cause of death in hospitals.

Each year, according to the Centers for Disease Control and Prevention, at least 1.7 million adults in the U.S.

develop sepsis, and at least 350,000 die as a result.

Sepsis is the main complication of severe CAP observed in approximately one in three patients with severe CAP.

Based on ANKTIVA’s documented ability to increase the proliferation of NK cells, CD8+ T cells and CD4+ T cells with no expansion of immunosuppressive Tregs, we have initiated a trial targeting CAP.

ResQ219-Community Acquired Pneumonia (CAP)

Trial Design:

Phase 2 Single Arm Trial

20 participants at U.S.

ANKTIVA + iNKT

Clinical trial protocol submitted to the FDA.

Glioblastoma Multiforme

According to the American Cancer Society, an estimated 24,740 new cases of malignant brain and nervous system tumors will be diagnosed in the U.S.

GBM is the most common malignant brain tumor, representing 52% of all primary brain tumors, and has a low five-year survival rate of approximately 7%.

Recurrent or Progressive GBM

Trial Design:

Multi-center, open-label Phase 2/2B trial evaluating ANKTIVA, PD-L1 CAR-NK (t-haNK), bevacizumab, and TTFields.

• Phase 2 portion is an open-label, single-arm study to evaluate the safety and efficacy of ANKTIVA, PD-L1 CAR-NK (t-haNK), and bevacizumab combination therapy in participants with recurrent or progressive GBM.

• Phase 2B portion is an open-label, randomized study to evaluate the efficacy and safety for the following 2 experimental arms in participants with recurrent or progressive GBM:

◦ ANKTIVA, bevacizumab, and TTFields combination therapy (Arm A)

◦ ANKTIVA, PD-L1 CAR-NK (t-haNK), bevacizumab, and TTFields combination therapy (Arm B)

14 participants were enrolled in the Phase 2 portion and 5 participants have been randomized in the Phase 2B portion.

Up to 20 participants will be randomized in Phase 2B (up to 10 participants/arm)

Results (January 2026, N=23 in pilot portion):

• Median Overall Survival:

Not yet reached with a median follow up of 6 months in the evaluable cohort

• Patients Alive:

19 of 23 enrolled (83%)

• Longest Survival from Recurrence:

12 months (ongoing)

• Baseline Mean ALC:

0.9 x × 10³ cells/μL (severe lymphopenia confirmed at enrollment)

• Mean ALC After One Cycle:

>1.4 × 10³ cells/µL (p<0.001, N=14)

• ALC Maintenance:

Statistically significant increases from baseline at all assessments through 20 weeks (p<=0.026)

• Total Doses Administered:

219 doses among 41 GBM patients (2L and 3L+) across QUILT-3.078 (N=23) and single-patient INDs (N=18)

• Treatment-Related Serious Adverse Events:

3 among 41 patients

• Cytokine Release Syndrome/Immune Effector Cell-Associated Neurotoxicity Syndrome:

None observed to date in this trial

Phase 2B cohort expansion underway with 8 patients enrolled.

Planned randomized registration trials include:

• Randomized Trial (Neoadjuvant Glioblastoma):

ANKTIVA + CAR-NK (PD-L1 t-haNK) versus standard of care

• Randomized Trial (Second Line Recurrent Glioblastoma):

ANKTIVA + CAR-NK (PD-L1 t-haNK) + bevacizumab + TTFields versus standard of care

Non-Hodgkin Lymphoma

According to the American Cancer Society, an estimated 79,320 people will be diagnosed with NHL, and 19,970 deaths will be attributed to the disease in 2026.

Macroglobulinemia

Trial Design:

Open-label Phase 1 single arm trial evaluating off-the-shelf allogeneic CD19 CAR-NK (t-haNK) in combination with rituximab for relapsed/refractory NHL (including Waldenström).

Up to 10 patients.

Results for Waldenström (January 2026):

• Durable Complete Responses:

7 and 15 months ongoing after only 8 doses (4 cycles)

• Disease Control:

100% in the first four subjects

• Administration:

All outpatient therapy, no hospitalization required

• Treatment-Related Serious Adverse Events:

None reported to date

One patient with 95% bone marrow infiltration by tumor cells achieved complete bone morphological remission after only four doses.

The complete response has been maintained for 15 months with no further treatment after eight total doses.

This regimen represents a chemotherapy-free and lymphodepletion-free approach, in contrast to currently approved autologous CAR-T therapies that require lymphodepleting chemotherapy and often inpatient hospitalization.

In addition to QUILT-106, based on the data and experience so far, the following trials have been initiated:

Relapsed Refractory NHL

Trial Design:

Single arm trial lymphodepletion

Flu/Cy + CAR-NK (CD19 t-haNK) + ANKTIVA + rituximab

Indolent Non-Hodgkin Lymphoma (Including Waldenström)

Trial Design:

Single arm trial, no lymphodepletion

CAR-NK (CD19 t-haNK) + ANKTIVA + rituximab

Planned Randomized Trial Relapsed/Refractory NHL

Trial Design:

Randomized lymphodepletion

• Flu/Cy + CAR-NK (CD19 t-haNK) + ANKTIVA + rituximab versus;

• Flu/Cy + CAR-NK (CD19 t-haNK) + rituximab

Additional Oncology Programs

Advanced Pancreatic Cancer (QUILT-88)

Exploratory Phase 1b/2 trials in patients with second-line or greater metastatic pancreatic cancer in which ANKTIVA was combined with off-the-shelf haNK cells, other agents, and SBRT showed encouraging results in patients with advanced disease.

The primary endpoints of the Phase 1b and 2 portions of the trials were safety and objective response rate, respectively.

In aggregate, 82% of patients (14/17) with advanced pancreatic cancer achieved disease control following combination therapy including ANKTIVA.

There were no ANKTIVA-related grade 3 or 4 adverse events reported.

On the basis of these exploratory trials, together with the preclinical findings that PD-L1 t-haNK is as active as haNK + anti-PD-L1 mAbs, we initiated a first-line through third-line pancreatic cancer clinical trial that uses PD-L1 t-haNK as described below:

• First-line advanced pancreatic cancer (Cohort A) .

Combination of ANKTIVA with low-dose chemotherapy plus SBRT with or without PD-L1 t-haNK vs.

gemcitabine/Abraxane ® as the standard-of-care control arm in this randomized trial.

• Second-line advanced pancreatic cancer (Cohort B) .

Combination of ANKTIVA with low-dose chemotherapy plus SBRT + PD-L1 t-haNK vs.

5FU/Onivyde ® as the standard-of-care control arm in this randomized trial.

• Third-line and beyond (Cohort C) .

Combination of ANKTIVA with low-dose chemotherapy plus SBRT + PD-L1 t-haNK in a single arm cohort of this trial with a primary endpoint of overall survival.

In October 2021, we announced that the trial’s Cohort C was fully enrolled.

Based on the strength of earlier data and the significant unmet medical need, we submitted an amendment to the FDA to increase enrollment in Cohort C.

As of January 2023, as reported at ASCO GI, the median overall survival in this highly advanced group of patients (who failed two to six prior lines of treatment) was 5.8 months (95% CI:

4.9, 6.4 months) exceeding the approximately two- to three-month historical median overall survival.

Of the 83 patients, 41 (49.4%) had progressed after two prior lines of therapy.

Median overall survival in this group was 6.3 months (95% CI:

5.0, 7.2 months), more than doubling the historical overall survival (survival of three months as reported by Manax et al.

ASCO GI 2019).

In Cohort C, grade 3 or greater treatment-related adverse events included anemia (32%), neutropenia (25%), thrombocytopenia (13%) and fatigue (7%) while all other grade 3 or greater treatment-related adverse events occurred at a frequency of less than 5%.

Table of Conten t s

On February 27, 2025, the FDA granted us RMAT designation for ANKTIVA and CAR-NK (PD-L1 t-haNK) in combination with standard-of-care chemotherapy/radiotherapy indicated for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer.

We intend to submit a BLA for the indication of reversal of lymphopenia in patients receiving standard-of-care chemotherapy and/or radiation and for the treatment of locally advanced or metastatic pancreatic cancer which includes the first-in-class CAR-NK (PD-L1 t-haNK), and to provide data from fully enrolled clinical trials in metastatic pancreatic cancer (QUILT 88) and in checkpoint relapsed NSCLC (QUILT 3055, NSCLC Cohort) patients, as well as lymphopenia reversal across multiple tumor types (QUILT 3055, all Cohorts), with supportive data of lymphocyte proliferation in healthy volunteers (QUILT 1004).

There can be no assurance that we will be successful in targeting the indication.

In 2026, an estimated 67,530 new cases of pancreatic cancer will be diagnosed in the U.S., with 52,740 deaths.

Pancreatic cancer is the third-leading cause of cancer-related deaths, with a five-year survival rate for late-stage cases of only 3%.

Trial Design:

Single arm Third-line and beyond (Cohort C) combination of ANKTIVA with low-dose chemotherapy plus SBRT + PD-L1 t-haNK

Primary Endpoint:

Overall survival.

Third Line and Beyond (Cohort C) Results (ASCO GI, January 2023):

• Median overall survival in patients with 2-6 prior lines:

5.8 months (95% CI:

4.9, 6.4) versus historical 2-3 months

• Median overall survival in patients after 2 prior lines (N=41):

6.3 months (95% CI:

5.0, 7.2) versus historical 3 months

• Grade 3+ treatment-related adverse events:

anemia (32%), neutropenia (25%), thrombocytopenia (13%), fatigue (7%)

In an update presented at ASCO 2025 (Abstracts #8054 Satoskar et al.

and #2663 Saleh et al.) 86 participants with third-to-sixth-line metastatic pancreatic cancer with high tumor burden (CA19-9 levels exceeding 34,000 IU/mL) highlighted:

• Lymphopenia Reversal (ALC >=1 × 10³ cells/µL):

Achieved in 67/86 subjects (78%)

• Survival Correlation:

Subjects with lymphopenia reversal had significantly prolonged median overall survival versus those remaining in severe lymphopenia (p=0.005;

hazard ratio 0.46;

• With Lymphopenia Rescue plus Lower Tumor Burden (CA19-9 <34,000 IU/mL):

median overall survival exceeded 10 months

As described above, in February 2025, the FDA granted us RMAT designation for ANKTIVA and PD-L1 CAR-NK (PD-L1 t-haNK) in combination with standard-of-care chemotherapy/radiotherapy for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer.

We are also initiating several planned clinical trials targeting pancreatic cancer including:

• ResQ108B-PANC:

Neoadjuvant locally advanced First Line single arm trial of ANKTIVA + zabadinostat + sotevtamab

• Randomized First Line Metastatic Pancreatic Cancer (trial design pending finalization)

▪ ANKTIVA + CAR-NK (PD-L1 t-haNK) + Abraxane + gemcitabine, versus

▪ Abraxane + gemcitabine

Colorectal Cancer and Lynch Syndrome (QUILT-5015, NCI-Sponsored)

In 2026, an estimated 158,850 new cases of colorectal cancer will be diagnosed in the U.S., with 55,230 deaths.

Notably, as of January 2026, colorectal cancer has become the leading cause of cancer death in men younger than 50 and the second leading cause in women of the same age group.

Lynch Syndrome:

The most common cause of hereditary colorectal cancer, causing approximately 4,300 colorectal cancers per year.

People with Lynch syndrome carry mutations in mismatch repair genes, and their close relatives have a 50% chance of inheriting the mutation.

Trial Design:

Phase 2 trial sponsored by the NCI evaluating ANKTIVA in combination with TriAd5 (human adenovirus serotype 5 (hAd5) vaccines targeting CEA, MUC1, and Brachyury) to reduce cancer onset incidence.

186 patients planned.

First two open-label phases fully accrued;

randomized controlled portion recruited 138 participants.

In addition to the NCI Lynch syndrome trial, we are also planning a randomized Phase 3 colorectal trial (ResQ203D-CRC) in patients undergoing resection/ablation of colorectal metastases with ANKTIVA in combination with zabadinostat + TEVIMBRA (anti-PD-1).

Human Papillomavirus (HPV) Clinical Trials

HPV-associated cancers represent a significant global public health burden, with an estimated more than 600,000 new HPV-driven cancer cases diagnosed worldwide each year, including cervical, head and neck, anal, vulvar, vaginal, and penile cancers, many of which have limited effective treatment options in the recurrent or advanced disease setting.

ImmunityBio has developed an investigational therapeutic vaccine program for HPV-associated malignancies utilizing a vector designed to deliver HPV E6 and E7 antigens and induce antigen-specific cellular immune responses in patients with established HPV driven cancers.

The hAd5 platform has demonstrated the ability in preclinical models to stimulate robust innate and adaptive immune activation directed against HPV expressing tumor cells.

QUILT-3.100 (HPV-Associated Cancers)

Trial Design:

Phase 1 open label clinical trial evaluating IBRX-042 (hAd5 [E6-E7]) in patients with HPV-associated cancers.

Up to 18 patients

The trial achieved its primary objectives, with satisfactory safety and tolerability observed across evaluated dose levels, supporting advancement of the program into subsequent clinical development.

ResQ-119A (Locally Advanced HPV-Positive Oropharyngeal Squamous Cell Carcinoma)

Trial Design:

Randomized, Phase 2A/2 clinical trial of ANKTIVA, IBRX-042 (hAd5 [E6-E7]) and Nab-Paclitaxel in locally advanced HPV-positive oropharyngeal squamous cell carcinoma, followed by definitive de-intensified intensity-modulated radiation therapy with concurrent Cisplatin compared to standard-of-care chemo-radiation.

This program exemplifies ImmunityBio’s broader strategy of leveraging viral vector technologies to activate immune mediated tumor control in cancers with significant unmet medical need.

M-ceNK in Solid Tumors

We have developed a memory-like cytokine-enhanced natural killer cell program, referred to as M-ceNK, designed to address immune dysfunction and treatment resistance observed in advanced malignancies.

The M-ceNK platform is based on the collection of peripheral blood mononuclear cells through standard apheresis procedures, which may be cryopreserved and stored for future manufacturing and clinical use, followed by ex vivo cytokine priming to induce durable metabolic and functional reprogramming of NK cells.

This process results in enhanced cytotoxicity, persistence, and immune activation following administration.

We have evaluated M-ceNK in early-stage clinical studies, including QUILT 3.076, which assess safety, feasibility, and immune activity of M-ceNK alone and in combination with other ImmunityBio immunotherapy platforms in patients with advanced solid tumors.

Prostate Cancer

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Prostate cancer is the second leading cause of cancer death in men with 36,320 deaths expected in 2026.

hAd5 PSA has been evaluated in combination with related recombinant hAd5-based cancer vaccines (hAd5 Brachyury and hAd5 MUC1) in a Phase 1 study in participants with mCRPC who had not responded to standard therapies (Bilusic 2021).

A total of 18 patients with mCRPC were enrolled and received at least one vaccination.

A total of 62 vaccinations were given.

The vaccine regimen was found to be well tolerable and safe with no DLTs.

The most common adverse events were grade 1 or grade 2 and included injection-site reaction (94.4% of participants), flu-like symptoms (58.8%), and fatigue (38.9%).

Treatment-related toxicities were uncommon and included grade 3 decreased lymphocyte count (n=2), grade 2 injection-site reaction (n=7), and grade 2 decreased lymphocyte count (n=1).

The recommended Phase 2 dose was determined to be 5×10 11 viral particles per dose.

Grade 3 significant adverse events included anemia, dehydration, hypotension, and lung infection.

No significant adverse events were related to study treatment.

We believe the combination of ANKTIVA, hAd5 PSA, M-ceNK cells, and standard-of-care in prostate cancer offers a unique opportunity to overcome resistance mediated by more than one mechanism, specifically, T cell exhaustion and human leukocyte antigen modulation.

The overall goals of the treatment regimen are to maximize immune cell death and augment and maintain the innate and adaptive immune responses against cancer cells.

High-Risk Prostate Cancer – ResQ110A

We have initiated a clinical trial to evaluate a new immunotherapy combination of ANKTIVA, hAd5 PSA, and M-ceNK in men with high-risk prostate cancer who have not had prostatectomy.

Participants will receive immunotherapy pre- and post-surgery.

This open-label study will enroll 20 patients and assess primary endpoints of event-free survival and biochemical recurrence-free survival post-surgery immunotherapy.

High-Risk Prostate Cancer – ResQ110B

We have also initiated a clinical trial to evaluate the immunotherapy combination of ANKTIVA, hAd5 PSA, and M-ceNK in men with high-risk prostate cancer who are ineligible for prostate surgery and receiving external beam radiation therapy.

This open-label study will enroll 20 patients and deliver the combination regimen prior to and after radiation therapy.

Primary outcomes are complete pathologic response after pre-radiation immunotherapy and prostate-specific antigen levels following post-radiation immunotherapy.

Glioblastoma Multiforme

According to the American Association of Neurological Surgeons, GBM is the most common malignant brain tumor accounting for approximately 48% of all primary brain tumors.

GBM has a low survival rate of approximately 40% in the first year after diagnosis and only 17% in the second year.

In a preclinical study, we evaluated the activity of ANKTIVA alone and in combination with an anti-PD-1 antibody or stereotactic radiosurgery in a murine GL261-luc GBM model and demonstrated that ANKTIVA as a monotherapy or combination therapy with an anti-PD-1 antibody exhibits a robust antitumor immune response resulting in prolonged survival including complete remission in tumor bearing mice.

In addition, treatment with ANKTIVA resulted in long-term immune memory against GBM tumor rechallenge.

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Recurrent or Progressive GBM – QUILT 3078

A multi-center, open-label Phase 2/3 trial has been initiated to evaluate the safety and efficacy of combination therapy with ANKTIVA, PD-L1 t-haNK, and bevacizumab in patients with recurrent or progressive GBM.

In Phase 2, safety of the combination will be assessed prior to Phase 3 wherein participants will be randomized to either combination therapy or bevacizumab monotherapy as the current standard of care.

• Pilot (Part A).

Enrollment will be initiated with a single-arm study of 10 patients to receive ANKTIVA, PD-L1 t-haNK, and bevacizumab combination therapy.

Continued development of the experimental arm in Part B will be based on the overall risk/benefit of the combined treatment regimen observed in Part A.

• Randomized Comparison of Combination Therapy vs.

Bevacizumab Monotherapy (Part B).

Part B will enroll patients to be randomly assigned (1:1) to the experimental arm or to the control arm.

The trial has enrolled patients with plans to enroll up to 20 patients.

Non-Hodgkin Lymphoma

The American Cancer Society estimates that 80,350 people will be diagnosed with NHL and 19,390 deaths will be attributed to the disease in 2025.

A Phase 1 trial evaluating ANKTIVA in combination with rituximab, an anti-CD20 mAb therapy, in patients with iNHL, who had relapsed or were refractory after two lines of therapy, was published in Clinical Cancer Research in 2021.

The combination regimen of ANKTIVA with rituximab was well tolerated with a single reported grade 4 adverse event and no reported grade 5 adverse events.

For patients with anti-CD20 mAb sensitive disease, the overall response rate in the SQ cohort was 78% (7 of 9) with 7 of 7 (100%) responses as complete remission.

NHL types can start in B cells or T cells with B cell lymphomas being more common.

Most B cell malignancies express high levels of CD19, including the majority of NHLs, such as diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma.

In addition, many leukemias express high levels of CD19, including B cell precursor acute lymphoblastic leukemia, chronic lymphocytic leukemia, and hairy cell leukemia.

As such, two CD19-directed CAR-T cell therapeutics are FDA-approved for use in a variety of indications including NHL and ALL.

Like T cells, NK cells can be genetically modified to express CARs that recognize tumor-associated cell-surface antigens and mediate specific recognition and lysis of cancer cells.

The CD19 t-haNK cell line combines the engineered enhancements of haNK cells with the expression of a CAR targeting CD19 and thus has the potential to demonstrate robust antibody-dependent cellular cytotoxicity antitumor activity against cancerous B cells and provide clinical benefit to patients with relapsed/refractory NHL.

Relapsed/Refractory Non-Hodgkin Lymphoma – QUILT 3092

We have initiated an open-label, Phase 1, first-in-human trial to evaluate the safety of CD19 t-haNK as a single agent and the safety and preliminary efficacy of CD19 t-haNK in combination with rituximab only and in combination with rituximab and ANKTIVA in subjects with relapsed/refractory NHL.

Ovarian Cancer

The American Cancer Society estimates that 20,890 women will be diagnosed with ovarian cancer and 12,730 deaths will be attributed to the disease in 2025.

A woman’s risk of getting ovarian cancer in her lifetime is about 1 in 91 and her chance of dying from ovarian cancer is about 1 in 143.

Platinum-Resistant Ovarian Cancer – ResQ209

Platinum-based chemotherapy is the standard-of-care for ovarian cancer;

however, 20-30% of patients have cancer recurrence following treatment and are considered platinum-resistant.

An open-label Phase 2 trial of ANKTIVA plus M-ceNK in patients with platinum-resistant ovarian cancer has been initiated.

In this trial, patients with platinum-resistant high-grade ovarian cancer will receive M-ceNK adoptive cell therapy in combination with ANKTIVA and gemcitabine.

Participants will undergo mononuclear cell collection for M-ceNK generation, day 8 induction and every 28-day (if M-ceNK are available) maintenance dosing, along with ANKTIVA.

Estimated enrollment is 20 participants.

Primary endpoints are progression-free survival using RECIST 1.1 criteria, overall survival, overall response rate, duration of response, disease control rate, and CA-125 levels.

Safety endpoints are adverse events, treatment-emergent adverse events and significant adverse events, graded using NCI Common Terminology Criteria for Adverse Events Version 5.0.

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Other Oncology Indications

In addition to the indications above, findings from completed QUILT studies, including the achievement of complete remissions in late-stage and advanced tumors of many types, such as MCC, TNBC, pancreatic cancer and head & neck cancer, validate the concept of eliciting immunogenic cell death rather than the tolerogenic cell death induced by current standards of care.

In addition to the trials listed above, we are exploring or pursuing several other company-sponsored and investigator-initiated studies of our product candidates including in colon cancer (hAd5 CEA, ANKTIVA), prostate cancer (ANKTIVA, hAd5 PSA), head and neck cancer (ANKTIVA, hAd5 CEA, hAd5 MUC1, hAd5 Brachyury), among others.

Infectious Disease Indications

In addition to the trials listed above in oncology, our approved product and other product candidates are being evaluated in several other company-sponsored and investigator-initiated studies in infectious diseases.

HIV affects tens of millions of people globally and while ART has increased the survival of infected HIV individuals, there is currently no cure.

One strategy for curing HIV is known as the “kick and kill” approach.

The “kick” is to induce HIV out of its latent resting state in T cells, revealing infected cells to the immune system, and the “kill” is to eliminate the infected cells via an immune response or immunotherapy.

ANKTIVA is a promising molecule to elicit “kick and kill” because of its ability to activate viral transcription in CD4+ T cells (“kick”) while strongly activating CD8+ effector memory cells and NK cells important for recognizing and killing HIV infected cells (“kill”), as well as directing these cells to sites of viral reservoirs.

ANKTIVA is being evaluated in investigator-initiated trials as a single agent and in combination with broadly neutralizing antibodies to control HIV in persons living with HIV and persons with acute HIV infection.

Active HIV Infection – University of Minnesota, National Institute of Allergy and Infectious Diseases

Based on the hypothesis that CD8+ T cells will migrate to B cell follicles and reduce the frequency of cells with an inducible HIV provirus in HIV-infected individuals treated with ANKTIVA, a Phase 1 proof-of-concept non-randomized, open-label dose-escalation clinical trial sponsored by the University of Minnesota in collaboration with the NIAID was conducted.

The primary assessment is the safety of ANKTIVA in ART-suppressed people living with HIV, along with exploratory analysis of effects on the HIV reservoir.

In a 2022 report, no significant laboratory adverse events attributable to ANKTIVA were recorded, and ANKTIVA was associated with proliferation and/or activation of CD4+ and CD8+ T cells and NK cells, with a small but significant decrease in the frequency of peripheral blood mononuclear cells with an inducible HIV provirus.

A separate small HIV Cure Phase 1 trial evaluating ANKTIVA in combination with haploidentical NK cells in HIV-infected patients was completed in 2023.

Reported data from the study validate the hypothesis that ANKTIVA combined with NK cells has the potential to reduce viral load in people living with HIV, showing a marked decrease in HIV-producing cells in lymph nodes.

The trial is complete, and results were published in May 2024.

The approach was well tolerated with no unexpected adverse events.

A follow-on trial is being planned to further investigate the above regimen in additional patients.

Active HIV Infection – National Institute of Allergy and Infectious Diseases, Rockefeller University

In June 2021, we announced the opening of a Phase 1 clinical trial sponsored by the AIDS Clinical Trials Group and the NIAID (the HIV Cure Study) that will evaluate whether ANKTIVA alone or together with bNAbs can control HIV following interruption of ART.

The Phase 1 open-label, randomized trial will enroll 46 people living with HIV whose virus has been suppressed by ART for approximately two years, including at least 30% cisgender women or transgender men.

This trial is actively enrolling as of January 2025.

An additional and companion Phase 1 trial utilizing ANKTIVA and 2 different bNAbs sponsored by The Rockefeller University opened in December 2022.

This trial completed enrollment as of January 2025.

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Acute HIV Infection – Thai Red Cross and the U.S.

Military HIV Research Program

In April 2021, we announced the launch of a Phase 2 trial sponsored by the Thai Red Cross and the U.S.

ResQ210 (Prostate Cancer - Biochemical Recurrence Localized Prostate)

Trial Design:

Randomized trial for radiation induced lymphopenia with radiation alone versus radiation with ANKTIVA.

Trial is currently in development.

Ovarian Cancer (ResQ209)

According to the American Cancer Society, 21,010 women will be diagnosed with ovarian cancer, and 12,450 deaths are expected in 2026.

Trial Design:

Open-label Phase 2 trial in patients with platinum-resistant high-grade ovarian cancer.

Apheresis followed by M-ceNK + ANKTIVA + gemcitabine

We are also evaluating M-ceNK in recurrent platinum-resistant high grade ovarian cancer in a Phase 2, open label, single arm trial that combines autologous M-ceNK adoptive cell therapy with a fixed dose of ANKTIVA and gemcitabine.

The trial is designed to assess safety and preliminary efficacy in a high unmet need population, with subjects undergoing standard apheresis for collection of mononuclear cells used to manufacture the M-ceNK product, which may be cryopreserved for administration per protocol.

Other indications

ImmunityBio is also evaluating ANKTIVA and other agents in multiple myeloma, HCC, and TNBC.

We are currently planning a single arm trial in relapsed multiple myeloma of a bispecific antibody and ANKTIVA (Mount Sinai Multiple Myeloma Network, Samir Parekh).

In addition, we plan to initiate a randomized Second line or greater HCC trial including ANKTIVA, zabadinostat and a CPI.

Finally, separately we completed QUILT-3.067 in TNBC which included ANKTIVA with our haNK in a single arm trial.

Based on these results we are initiating a new Second Line or greater randomized TNBC trial that includes ANKTIVA, our PD-L1 CAR-NK (t-haNK) and a TROP2 antibody.

Trial design is pending finalization.

INFECTIOUS DISEASE PROGRAMS

HIV affects tens of millions of people globally.

While ART has increased survival, there is no cure.

One research strategy is the “kick and kill” approach:

induce HIV out of its latent state to reveal infected cells, then eliminate them via immune response.

ANKTIVA’s mechanism of action may support this approach by activating viral transcription in CD4+ T cells, strongly activating CD8+ effector memory cells and NK cells, and promoting their trafficking to viral reservoir sites.

• University of Minnesota/NIAID:

Phase 1 trial in ART-suppressed patients.

Results showed a small but statistically significant decrease in the frequency of cells with inducible HIV provirus.

• NIAID/Rockefeller University (HIV Cure Study):

Phase 1 randomized trial (N=46) evaluating whether ANKTIVA alone or with broadly neutralizing antibodies can control HIV following ART interruption.

• Thai Red Cross/U.S.

Military HIV Research Program:

The trial enrolled 14 patients and was designed to investigate the safety, tolerability and immunostimulatory effects of administering ANKTIVA during acute HIV infection.

ANKTIVA was administered subcutaneously at weeks zero, three and six (for a total of three doses) and was initiated together with antiretroviral therapy in order to determine if the immunostimulatory effects of ANKTIVA will reduce the amount of HIV present during acute infection.

The trial duration for individual participants was approximately 12 weeks.

It is hypothesized that ANKTIVA initiated with anti-retroviral therapy during acute HIV infection will not result in complications or additional toxicities compared with anti-retroviral therapy alone and may result in a reduced viral load in these patients by inhibiting early establishment of HIV reservoirs in infected individuals.

The trial was recently completed, and data analyses are ongoing.

Other Infectious Diseases

We previously developed COVID-19 vaccine candidates based on our hAd5 platform that delivered DNA for SARS-CoV-2 spike (S) and nucleocapsid (N) proteins that underwent early clinical testing in the U.S.

and South Africa.

These trials demonstrated the tolerability of the platforms, which elicited no severe adverse events, and provided evidence of effective antigen delivery.

We remain interested in forwarding the idea of a universal nucleocapsid vaccine.

Studies on long-term immune responses to SARS-CoV-1, a virus very similar to SARS-CoV-2, have shown that T cell responses to the N protein can provide long-term immunity up to at least 11 years after infection.

An N-based vaccine would also overcome the problem of the rapid mutation of S, which renders vaccines less effective over time and necessitates continuous re-design.

Because of the cross-reactivity to N from SARS-CoV-1 and -2, we believe a ‘pan-SARS-CoV’ vaccine is possible.

This strategy is crucial for developing a universal vaccine that can preemptively address the threat of new coronavirus outbreaks, ensuring long-term and wide-ranging immunity.

Centers for Disease Control and Prevention have described long COVID as a chronic condition that remains a serious public health concern.

Given the consistent observation of altered immune cell persistence and function in persons experiencing symptoms of long COVID, we are exploring the potential value of ANKTIVA and our vaccine candidates in restoring immune cell function in the millions of people at risk for long COVID.

Current evidence suggests long COVID may be due, in part, to persistence of SARS-CoV-2 virus in tissues and that both NK and T cell function are aberrant, resulting in persistent inflammation, damage to the blood-brain barrier, and long COVID symptoms.

If this model is correct, then ANKTIVA-mediated enhancement of innate and adaptive immune responses against virus replication or residual virus-infected cells across tissues could improve long COVID symptoms.

Phase 2 trial (N=14) investigating ANKTIVA during acute HIV infection.

Trial completed, data analyses ongoing.

The CDC has described Long COVID as a chronic condition that remains a public health concern.

Long COVID may be linked to the persistence of SARS-CoV-2 in tissues, with aberrant NK and T cell function leading to persistent inflammation.

COVID-4.019-Long:

Phase 2 study (announced August 2025) assessing ANKTIVA in patients meeting World Health Organization Long COVID criteria.

Single-arm safety study with up to 40 participants.

MANUFACTURING AND DISTRIBUTION

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In addition, we plan to further enhance our in-house manufacturing capabilities for drug substance, drug products, and labeling and packaging.

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Overview of our Manufacturing Model

Our manufacturing capabilities include advanced technological facilities to produce and test various drug substances and drug products.

Our experienced operations and quality team focuses on internal manufacturing and testing with a commitment to create robust, high quality, efficient and consistent supply that meets target product profiles.

We believe our Phase 1 manufacturing process is designed to efficiently scale-up through all phases of clinical development to commercial manufacturing to drive successful commercialization.

Our manufacturing capabilities include advanced facilities that produce and test various drug substances, drug products, and cell therapies.

Our experienced operations and quality team focuses on internal manufacturing and testing with a commitment to creating robust, high quality, efficient and consistent supply that meets target product profiles.

We believe our Phase 1 manufacturing process is engineered to scale efficiently through all clinical-development stages to commercial production.

Commercial cGMP Production

On April 22, 2024, the FDA approved our product, ANKTIVA with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors.

In April 2024, the FDA approved our product, ANKTIVA with BCG for the treatment of adult patients with BCG-unresponsive NMIBC CIS with or without papillary tumors.

We have contracted with multiple multi-national biologics manufacturers with several cGMP-compliant facilities in the U.S., Europe and Asia for production of ANKTIVA for commercial sale and for use in our clinical trials.

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We believe the facilities used for our commercial sales and clinical trials have robust process development and validation and quality oversight with high-capacity production suites operating multiple 2,000-20,000L production bioreactors and high-capacity fill lines.

We previously received a CRL from the FDA in May 2023 in response to our initial BLA submission citing deficiencies related in part to the FDA’s pre-license inspection of our third party CMOs.

We worked with our CMOs to address the issues raised, resubmitted our BLA in October 2023, and the FDA approved ANKTIVA with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors on April 22, 2024.

Clinical Trial GMP Antibody and Fusion Protein Production

We are committed to the goal of establishing a cGMP-compliant multi-platform facility in California, which includes a large space for the production of antibodies and fusion proteins (including ANKTIVA) to treat cancers and infectious diseases.

We plan for this facility to include fully integrated biologic upstream and downstream production suites and a quality assurance/quality control release laboratory for high-capacity antibody and fusion protein production.

We may also potentially use CMOs for our fusion protein candidates.

We remain committed to establishing a cGMP-compliant multi-platform facility that will house large-scale production of antibodies and fusion proteins (including ANKTIVA) for oncology and infectious disease indications.

The facility will feature fully-integrated upstream and downstream biologic production suites and a quality assurance/quality control release laboratory.

We may also engage CMOs for select fusion protein candidates.

Clinical Trial GMP Adenovirus

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Clinical Trial GMP NK Cell Therapy Production

We have established other facilities for NK cell therapy product production in multiple sites in California for oncology.

We are committed to the goal of complying with cGMP at these facilities.

One of our sites in California is dedicated to our off-the-shelf product candidates (including PD-L1 t‑haNK and CD19), while another is primarily focused on our M-ceNK product candidates, including a training lab for our second-generation offerings.

We are in the process of reviewing our expansion efforts for both our t-haNK and M-ceNK manufacturing capacity with the goal to increase our ability to supply our clinical trials and/or EAPs, as applicable.

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We have established NK cell therapy manufacturing facilities at multiple California sites dedicated to our oncology programs and are committed to maintaining cGMP compliance at these facilities.

One site is dedicated to our off-the-shelf product candidates (including PD-L1 and CD19 CAR-NKs), while another is primarily focused on our M-ceNK product candidates and includes a training lab for our second-generation candidates.

We are evaluating our expansion plans for both our CAR-NK (t-haNK) and M-ceNK manufacturing capacity in both the U.S.

and globally to enhance our ability to supply our clinical trials, and where appropriate RMAT designation and EAPs, as applicable.

We believe we are at the forefront of cell therapy innovation and are working to aggressively implement mass scaling robotic and automation technology along with artificial intelligence to scale our platform globally.

cGMP ISO Class 5 Manufacturing Facility

On February 14, 2022, we acquired a leasehold interest in the Dunkirk Facility.

This facility has construction needs that may require an additional 12 to 18 months to complete in order for it to be used as intended.

These construction needs remain as a result of an ongoing dispute with the Dunkirk Facility’s general contractor and a stay in resolving the dispute related to Athenex’s ongoing bankruptcy proceedings.

In addition, and related to the delayed completion of the facility as described above, in November 2024 we received written notice from our landlord alleging non-compliance with the initial employee headcount requirement of our lease for the Dunkirk Facility.

While we are seeking to resolve this matter expeditiously, there can be no assurance that we will succeed in doing so, and we may lose access to the Dunkirk Facility.

“Risk Factors— We are party to a public-private partnership regarding our manufacturing facility in Dunkirk, New York, and if we or our counterparties fail to meet the obligations of those agreements, it could materially impact our development, operations and prospects ” for more information.

We believe this facility has the potential to provide us with a state-of-the-art biotech production center that will substantially expand and diversify our existing manufacturing capacity in the U.S.

We believe our leasehold interest in the Dunkirk Facility has the potential to provide us with a state-of-the-art biotech production center that will expand and diversify our existing manufacturing capacity in the U.S.

and the ability to scale production associated with certain of our product candidates.

“Risk Factors— We are party to a public-private partnership regarding our manufacturing facility in Dunkirk, New York, and our failure to meet the obligations of those agreements could materially impact our development, operations and prospects.

Manufacture of Platform Product Candidates

ImmunityBio’s diverse product candidate portfolio and pipeline requires a broad knowledge of various manufacturing and quality assurance methods.

We have invested heavily in the processes, systems, and technology to build an extensive range of manufacturing programs spanning various levels of development from IND-enablement through BLA preparation for our other product candidates.

We believe our plan to selectively use third-party CMOs for certain of our assets at various stages, coupled with internal development, will give us assurance that any products will have backup manufacturing options.

In connection with the approval of our product, ANKTIVA with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors, by the FDA on April 22, 2024, we engaged a leading third-party logistic provider in a title model to enable commercial distribution.

We began commercial distribution of our approved product in May 2024.

Our diverse pipeline of products and candidates requires a broad knowledge of various manufacturing and quality assurance methods.

We have invested heavily in the processes, systems, and technology to establish an extensive range of manufacturing programs spanning various levels of development from IND-enablement through BLA preparation for our Cancer BioShield platform.

We believe our strategy of selectively leveraging third-party CMOs for certain of our assets at various stages, coupled with internal development, gives us assurance that any products will have backup manufacturing options.

Marketing and Distribution

In connection with the approval of our product, ANKTIVA, by the FDA in April 2024, we continue building out our differentiated commercial infrastructure, including seasoned branding, marketing, sales, medical affairs, and market access teams initially focused in the urology space.

We began commercial distribution of our approved product in May 2024 and have engaged a leading third-party logistics provider in a title model to enable commercial distribution.

We have contracted with large specialty distributors and a large specialty pharmacy provider to make our commercial product available across relevant clinics, hospitals, infusion centers, and government entities.

We face potential competition from many different sources, including major and specialty pharmaceutical and biotechnology companies, academic research institutions, governmental agencies, and public and private research institutions.

The biotechnology and pharmaceutical industries are intensely competitive.

We face competition from major, specialty, and biotechnology pharmaceutical companies worldwide.

Our approved product and other product candidates that we successfully develop and commercialize will compete with current therapies and new therapies that may become available in the future.

We believe that the key competitive factors affecting the success of our approved product and other product candidates will include efficacy, safety profile, convenience, cost, market access, commercial efforts, competition, and intellectual property protection.

We have focused our efforts on oncology indications, with a primary focus on urology, and secondarily, infectious disease indications that are difficult to treat and with large unmet needs, and we believe our platform will be broadly applicable across multiple tumor types and infections.

Based on the breadth and depth of our platforms, we believe our competitors will range from large pharmaceutical companies to emerging novel biotechnology companies.

• Cytokine Fusion Proteins.

This platform primarily competes with large pharmaceutical companies marketing CPIs.

However, the potential exists for some of these large pharmaceutical companies to seek collaboration for the combination of ANKTIVA with their marketed CPI.

In the context of NMIBC, we currently compete with Ferring Pharmaceuticals and Merck & Co., Inc.

(Merck), and may compete with CG Oncology Inc., enGene Holdings Inc., Janssen Pharmaceuticals, Inc.

(Janssen)/Johnson & Johnson, and UroGen Pharma, Inc.

in the future.

We believe this platform will also compete across oncological indications with immunotherapy fusion protein companies developing similar approaches, including Nektar Therapeutics, Neoleukin Therapeutics, Inc., Novartis International AG (Novartis), F.

Hoffmann-La Roche AG (Roche), Sanofi, S.A., and Xencor, Inc.

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• DNA and Recombinant Protein Vaccines .

This platform and the associated product candidates will likely compete with other cancer vaccines.

Other potential cancer vaccine competitors include Achilles Therapeutics, BioNTech SE (BioNTech), Geneos Therapeutics, Inc., Hangzhou Neoantigen Therapeutics, Inc., Merck, Moderna, Inc.

(Moderna), and Roche.

• Cell Therapies.

This platform’s product candidates (t‑haNK and M-ceNK) face competition from several companies focused on NK cell-based approaches, including Artiva Biotherapeutics Inc., Catamaran Bio Inc., Century Therapeutics, Inc., Fate Therapeutics, Inc., Gamida Cell, Ltd., INmune Bio Inc., Nkarta Therapeutics, Inc., NKGen Biotech, Inc., and Shoreline Biosciences, Inc.

In addition, our NK cell product candidates compete with other cell and molecule-based immunotherapy approaches using or targeting NK cells, NKT cells, T cells, macrophages, and dendritic cells.

There are currently seven approved CAR-T cell-based treatments marketed by Autolus Therapeutics, plc (Autolus), Bristol-Myers Squibb Company (BMS) (two marketed products), Gilead Sciences, Inc.

(Gilead)/Kite Pharma (two marketed products), Janssen/Johnson & Johnson, and Novartis.

Additional companies focused on CAR T-related treatment approaches include Allogene Therapeutics, Inc., BMS, Cellectis SA, Celularity, Inc., Gilead, Janssen, Novartis, Pfizer, Inc.

(Pfizer), and Poseida Therapeutics, Inc./Roche.

There is also one approved TIL therapy from Iovance Biotherapeutics, Inc.

Competitor companies focused on other T cell-based approaches include Adaptimmune Ltd.

(with an approved TCR-T cell therapy), Adicet Bio, Inc., Autolus, Beam Therapeutics Inc., BioNTech, GlaxoSmithKline plc.

(GSK), Sensei Biotherapeutics, Inc., and Senti Biosciences, Inc.

Infectious Diseases

Currently in infectious disease, ANKTIVA is being used in investigational trials primarily focused on HIV and, if approved, will likely compete with companies who have approved therapeutics for HIV, including Gilead, ViiV Healthcare Limited (a joint venture between GSK, Pfizer, and Shionogi, Inc.), Merck, BMS, and Janssen/Johnson & Johnson).

Additionally, we are exploring the potential value of ANKTIVA and our vaccine candidates in restoring immune cell function in the millions of people at risk for long COVID.

These efforts face competition from companies that include Pfizer, Moderna, AIM ImmunoTech, Inc., and Laurent Pharmaceuticals and also efforts to expand the label for approved generic medicines for the treatment of long COVID.

Competitive Landscape by Indication

Current Standard of Care:

BCG (TICE ® BCG, Merck) has been the standard treatment for decades but is subject to chronic supply shortages.

Approved Therapies:

Beyond ANKTIVA being approved for BCG-unresponsive NMBIC CIS with or without papillary tumors, pembrolizumab (KEYTRUDA, Merck), nadofaragene firadenovec-vncg (ADSTRILADRIN ® , Ferring), and INLEXZO ® (Janssen Biotech, Inc., a Johnson & Johnson company) are approved for BCG-unresponsive NMIBC CIS in patients ineligible for, or who have elected not to undergo, cystectomy.

Development Stage:

Several therapies are in clinical development for BCG-unresponsive NMIBC.

Our Position:

ANKTIVA is approved in four jurisdictions for BCG-unresponsive NMIBC.

Our clinical data demonstrate durable complete responses lasting up to 54 months, with high rates of bladder preservation.

We believe our partnership with Serum Institute has the potential to alleviate U.S.

BCG supply constraints.

Established Therapies:

CPIs, including pembrolizumab (KEYTRUDA, Merck), nivolumab (OPDIVO ® , Bristol Myers Squibb), and atezolizumab (TECENTRIQ ® , Roche), are established treatments for NSCLC.

Emerging Therapies:

Various combination regimens and bispecific antibodies are in development.

Our Position:

ANKTIVA received accelerated approval from the SFDA in January 2026 for the treatment of metastatic NSCLC in combination with CPIs.

Our clinical data demonstrate an association between lymphocyte restoration and improved survival, supporting a differentiated mechanism of action.

Approved CAR-T Products:

Multiple autologous CAR-T products are approved, including tisagenlecluecel (KYMRIAH ® , Novartis), axicabtagene ciloleucel (YESCARTA ® , Kite/Gilead), lisocabtagene maraleucel (BREYANZI ® , Bristol Myers Squibb), idecabtagene vicleucel (ABECMA ® , Bristol Myers Squibb), and ciltacabtagene autoleucel (CARVYKTI ® , Janssen/Legend).

These products require lymphodepleting chemotherapy and are often administered in inpatient settings.

Our Position:

Our off-the-shelf CAR-NK platform is being evaluated in clinical trials without lymphodepleting chemotherapy and are administered in outpatient settings.

To date, we have not observed cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome in our CAR-NK trials, though our clinical experience remains limited.

IL-15 Agonists

As of December 31, 2025, based on publicly available information, ANKTIVA is the only FDA-approved IL-15 receptor superagonist.

Several biotechnology companies are developing IL-15-based therapies at various stages of clinical development.

There can be no assurance that we will maintain any competitive advantages as other IL-15 therapies advance in development.

INTELLECTUAL PROPERTY

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We have developed, acquired, and in-licensed patents and patent applications across platforms as previously described for activated NK and T cells, and memory T cell activation.

With respect to activated NK and T cells, we have developed N-803, an N72D variant IL-15 complexed to a dimeric IL-15Ra/Fc fusion protein and with respect to memory T cell activation, we have developed adenoviral immunotherapies expressing TAAs such as CEA, MUC1, and Brachyury.

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With respect to activated NK and T cells, we have developed N-803, an N72D variant IL-15 complexed to a dimeric IL-15Rα/Fc fusion protein and with respect to memory T cell activation, we have developed adenoviral immunotherapies expressing TAAs such as CEA, MUC1, and Brachyury.

As of December 31, 2025, we own patents and patent applications related to the development and commercialization of N-803 in the U.S.

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• haNK cells;

• EGFR t-haNK cells;

• CD19 t-haNK cells;

• HER2 t-haNK cells;

• PD-L1 t-haNK cells.

• EGFR NK-CAR;

• CD19 NK-CAR;

• HER2 NK-CAR;

• PD-L1 CAR-NK.

As of December 31, 2025, we own patents and patent applications related to development and commercialization of multi-functional antibody-based cytokine fusion proteins targeting the IL-12 pathway, the IL-15 pathway, TGF-ß, PD-L1 and CD20 in the U.S.

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For example, these patents and patent applications include claims directed to fusions of human transforming growth factor receptor and/or IL-15 with tissue factor.

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As of December 31, 2025, we exclusively own, and co-own with and in-license from the HHS, patents and patent applications related to the development and commercialization of adenovirus-based cancer and viral immunotherapies, in the U.S.

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In particular, our ability to stop third parties from making, using, selling, offering to sell, or importing products that infringe our intellectual property will depend in part on our success in obtaining and enforcing patent claims that cover our technology, inventions, and improvements.

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granted in the future will be commercially useful in protecting our approved product and other product candidates and the methods used to manufacture our approved product and those other product candidates.

Moreover, even our issued patents do not guarantee us the right to practice our technology in relation to the commercialization of our approved product and other product candidates.

With respect to both licensed and owned intellectual property, we cannot be sure that patents will be granted with respect to any current pending patent applications or with respect to any patent applications filed in the future, nor can we be sure that any existing patents or any patents that may be granted in the future will be commercially useful in protecting our approved product and other product candidates and the methods used to manufacture our approved product and those other product candidates.

Moreover, even our issued patents do not guarantee us the right to practice our technology in relation to the commercialization of our approved product and other product

The area of patent and other intellectual property rights in biotechnology is an evolving one with many risks and uncertainties, and third parties may have blocking patents that could be used to prevent us from commercializing our approved product and other product candidates and practicing our technology.

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Under this agreement, we agreed to pay NCI funding totaling $1.3 million per year, payable in semi-annual installments each year through 2025.

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Serum Institute of India Private Limited

In May 2024, we announced an exclusive global arrangement with Serum Institute, the world’s largest manufacturer of vaccines by number of doses produced, to supply us with rBCG for use exclusively in combination with our ANKTIVA product, subject to regulatory approvals.

Serum Institute’s GMP capacity to manufacture large-scale volumes of BCG, already tested for safety and efficacy in clinical trials in Europe in subjects with NMIBC, aims to address the shortage of TICE BCG, which we believe will help to ensure a reliable supply for patients in need.

In addition, we are testing rBCG in an FDA-approved clinical trial (ResQ133A) of intravesical rBCG in participants with NMIBC eligible to receive TICE BCG.

In February 2025, the FDA authorized an EAP (ResQ132EX-NMIBC) allowing us to provide rBCG developed by Serum Institute to urologists to address the TICE BCG shortage in all settings where the TICE BCG label is approved.

Shipments of rBCG pursuant to the EAP began during the first quarter of 2025.

In addition, we filed an IND, and the FDA provided a Study May Proceed Notification for a clinical trial (ResQ133A-NMIBC) of intravesical rBCG in participants with NMIBC eligible to receive TICE BCG.

BeiGene, Ltd.

In January 2025, we announced a collaboration and supply agreement with BeiGene, Ltd.

BeOne Medicines Ltd.

In January 2025, we announced a collaboration and supply agreement with BeOne, a global oncology company, to conduct a confirmatory randomized Phase 3 clinical trial (ResQ201A-NSCLC), combining BeOne’s tislelizumab, a PD-1 CPI, and ANKTIVA.

The Phase 3 ResQ201A-NSCLC study aims to confirm the efficacy and safety of combination ANKTIVA plus CPI therapy previously demonstrated in the QUILT-3.055 trial and provide evidence of the potential for these two immunotherapeutic agents to improve overall survival in patients with advanced or metastatic NSCLC who have acquired resistance to immune CPI therapy.

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We have licensed rights to 3M-052, a synthetic TLR7/8 agonist, 3M-052 formulations and related technology from 3M IPC and its affiliates and AAHI.

In November 2021 we obtained nonexclusive rights in the field of SARS-CoV-2 and in June 2022 we modified those rights and expanded the scope of the license to include (1) SARS-CoV-2 and other infectious diseases including malaria, HIV, tuberculosis, hookworm and varicella zoster on an exclusive basis in countries other than LMIC, and (2) oncology applications, when used in combination with our proprietary technology and/or IL-15 receptor superagonists.

Adjuvants are either synthetic or naturally occurring molecules that activate TLRs thereby enhancing the humoral and cell-mediated immune response of vaccines.

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The synthetic imidazoquinolinone 3M-052 is structurally similar to resiquimod.

The 3M-052/Alum adjuvant formulation is in Phase 1 trials in the U.S.

with an HIV antigen and has been well-tolerated and immunogenic.

The 3M-052/Alum adjuvant formulation completed Phase 1 trials in the U.S.

with an HIV antigen and was well-tolerated and immunogenic.

In consideration for the license, we agreed to make certain periodic license payments, including $2.25 million each year through June 2025.

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We may terminate this agreement, in whole, or on a licensed-product-by-licensed-product and/or country-by-country basis, at any time upon sixty (60) days’ written notice to GlobeImmune.

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Sanford Health

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Sanford may terminate the agreement in the event of an uncured material breach by us.

In June 2023, we filed an IND for QUILT 3100 exploring the use of an hAd5 [E6/E7] construct known as IBRX-042 in a Phase 1 open-label trial to evaluate safety and determine the MTD in subjects with HPV-associated tumors.

During the second half of 2023, we received correspondence from the FDA that it was placing the IND on clinical hold and requesting additional toxicology studies.

The company submitted a complete response to the hold letter, and the clinical hold was removed in March 2024.

The first patient was enrolled in August 2024, satisfying a commercial milestone.

Enrollment for the trial continues at three active clinical sites.

In June 2023, we filed an IND for QUILT-3.100 exploring the use of an hAd5 [E6/E7] construct known as IBRX-042 in a Phase 1 open-label trial to evaluate safety and determine the maximum tolerated dose in subjects with HPV-associated tumors.

A first patient was enrolled in a Phase 1 trial in August 2024, satisfying the first commercial milestone.

The second commercial milestone was satisfied in December 2025 related to the enrollment progress of a first patient in a Phase 2 trial.

Shenzhen Beike Biotechnology Co.

In 2014, Altor entered into a license, development and commercialization agreement with Beike, which agreement was amended and restated in 2017, pursuant to which Altor granted to Beike an exclusive license under certain of its intellectual property rights in order to use, research, develop and commercialize products based on ANKTIVA in China for human therapeutic uses, in exchange for consideration that includes up to $195.5 million in total milestone payments based on the successful completion of regulatory and sales milestones for each resulting product, and a royalty on net sales of licensed products, on a product-by-product basis ranging in percentage from the mid-single digits to the mid-teens.

In 2014, Altor entered into a license, development and commercialization agreement with Beike, which was amended and restated in 2017, pursuant to which Altor granted to Beike an exclusive license under certain of its intellectual property rights in order to use, research, develop and commercialize products based on ANKTIVA in China for human therapeutic uses, in exchange for consideration that includes up to $195.5 million in total milestone payments based on the successful completion of regulatory and sales milestones for each resulting product, and a royalty on net sales of licensed products, on a product-by-product basis ranging in percentage from the mid-single digits to the mid-teens.

Beike’s obligation to pay royalties continues, on a licensed product-by-licensed product basis, until the later of (i) the date on which such licensed product is no longer covered by a valid claim of a patent licensed pursuant to the agreement in China and (ii) ten years after the first commercial sale of such licensed product in China.

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In the U.S., the FDA regulates biopharmaceuticals under the FD&C Act and the PHSA.

Biopharmaceuticals also are subject to other federal, state, and local statutes and regulations.

Biopharmaceuticals are also subject to other federal, state, and local statutes and regulations.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.

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Any of these actions or events could have a material impact on the availability of our product candidates.

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The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of small molecule and biologics such as those we are developing.

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generally involves the following:

• completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s GLP guidelines;

• completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s Good Laboratory Practice guidelines;

• submission to the FDA of an IND, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made;

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Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.

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Further, the FDA’s “real-time” release of newly issued CRLs associated with withdrawn or abandoned applications, if applicable to any of our product candidates, can materially impact our business and competitive advantage.

When a clinical trial using genetically engineered cells is conducted at, or sponsored by, institutions receiving NIH funding for wild-type DNA research, prior to the submission of an IND to the FDA, a protocol and related documentation is submitted to and the study is registered with the OBA pursuant to the NIH Guidelines.

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Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

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BLA/NDA Submission and Review by the FDA

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In addition, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our product candidates under development.

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A sponsor may seek approval of its product candidate under programs designed to accelerate the FDA’s review and approval of new drugs and biological products that meet certain criteria.

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or post-approval monitoring of all patients treated with such therapy prior to its approval.

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Breakthrough Therapy, Fast Track and RMAT designations and priority review do not change the standards for approval.

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Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.

We cannot be certain that we or our present or future suppliers will be able to comply with cGMP regulations and other FDA regulatory requirements.

We cannot be certain that we or our present or future suppliers will be able to comply with cGMP

regulations and other FDA regulatory requirements.

If our present or future suppliers are not able to comply with these requirements, the FDA may, among other things, halt our clinical trials, require us to recall a product from distribution, or withdraw approval of the BLA or NDA.

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In the U.S., once a drug is approved, its manufacture is subject to comprehensive and continuing regulation by the FDA.

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Discovery of problems with a drug after approval may result in restrictions on a drug, manufacturer, or holder of an approved NDA, including, among other things, recall or withdrawal of the drug from the market, and may require substantial resources to correct.

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The FDA may also require post-approval testing, sometimes referred to as Phase 4 testing, risk minimization action plans, and post-marketing surveillance to monitor the effects of an approved drug or place conditions on an approval that could restrict the distribution or use of the drug.

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Prescription drug promotional materials must be submitted to the FDA in conjunction with their first use.

Any distribution of prescription drugs and pharmaceutical samples must comply with the U.S.

PDMA, a part of the FD&C Act.

Any distribution of prescription drugs and pharmaceutical samples must comply with the PDMA, a part of the FD&C Act.

The DSCSA, enacted in 2013, aims to build an electronic system to identify and trace certain prescription drugs distributed in the U.S.

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Drug manufacturers and their collaborators are also required to place a unique product identifier on prescription drug packages.

Premarket Clearance and Approval Requirements for Medical Devices

Pre-market Clearance and Approval Requirements for Medical Devices

Each medical device we seek to commercially distribute in the U.S., including our bioreactors, will require a prior 510(k) clearance, unless it has received a PMA from the FDA.

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and good manufacturing practices.

Most Class 1 devices are classified as exempt from premarket notification under section

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Most Class 1 devices are classified as exempt from pre-market notification under section

510(k) of the FD&C Act and therefore may be commercially distributed without obtaining 510(k) clearance from the FDA.

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Special controls include performance standards, post market surveillance, patient registries and guidance documents.

A manufacturer may be required to submit to the FDA a premarket notification requesting permission to commercially distribute some Class 2 devices.

A manufacturer may be required to submit to the FDA a pre-market notification requesting permission to commercially distribute some Class 2 devices.

Devices deemed by the FDA to pose the greatest risk, such as life-sustaining, life-supporting or implantable devices, or devices deemed not substantially equivalent to a previously cleared 510(k) device, are placed in Class 3.

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However, there are some Class 3 devices for which the FDA has not yet called for a PMA.

For these devices, the manufacturer must submit a premarket notification and obtain 510(k) clearance in orders to commercially distribute these devices.

For these devices, the manufacturer must submit a pre-market notification and obtain 510(k) clearance in orders to commercially distribute these devices.

The FDA can also impose sales, marketing, or other restrictions on devices in order to ensure that they are used in a safe and effective manner.

510(k) Clearance Pathway

When a 510(k) clearance is required, we must submit a premarket notification to the FDA demonstrating that our proposed device is substantially equivalent to a predicate device, which is a previously cleared and legally marketed 510(k) device or a device that was in commercial distribution before May 28, 1976.

By regulation, a premarket notification must be submitted to the FDA at least 90 days before we intend to distribute a device.

When a 510(k) clearance is required, we must submit a pre-market notification to the FDA demonstrating that our proposed device is substantially equivalent to a predicate device, which is a previously cleared and legally marketed 510(k) device or a device that was in commercial distribution before May 28, 1976.

By regulation, a pre-market notification must be submitted to the FDA at least 90 days before we intend to distribute a device.

As a practical matter, clearance often takes significantly longer.

To demonstrate substantial equivalence, the manufacturer must show that the proposed device has the same intended use as the predicate device, and it either has the same technological characteristics, or different technological characteristics and the information in the premarket notification demonstrates that the device is equally safe and effective and does not raise different questions of safety and effectiveness.

To demonstrate substantial equivalence, the manufacturer must show that the proposed device has the same intended use as the predicate device, and it either has the same technological characteristics, or different technological characteristics and the information in the pre-market notification demonstrates that the device is equally safe and effective and does not raise different questions of safety and effectiveness.

The FDA may require further information, including clinical data, to make a determination regarding substantial equivalence.

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This procedure allows a manufacturer whose novel device is automatically classified into Class 3 to request down-classification of its medical device into Class 1 or Class 2 on the basis that the device presents low or moderate risk, rather than requiring the submission and approval of a PMA application.

Prior to the enactment of the FDASIA, a medical device could only be eligible for De Novo classification if the manufacturer first submitted a 510(k) premarket notification and received a determination from the FDA that the device was not substantially equivalent.

The FDASIA streamlined the De Novo classification pathway by permitting manufacturers to request De Novo classification directly without first submitting a 510(k) premarket notification to the FDA and receiving a not substantially equivalent determination.

Prior to the enactment of the FDASIA, a medical device could only be eligible for De Novo classification if the manufacturer first submitted a 510(k) pre-market notification and received a determination from the FDA that the device was not substantially equivalent.

The FDASIA streamlined the De Novo classification pathway by permitting manufacturers to request De Novo classification directly without first submitting a 510(k) pre-market notification to the FDA and receiving a not substantially equivalent determination.

Under the FDASIA, the FDA is required to classify the device within 120 days following receipt of the De Novo application.

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In addition, the FDA may reject the reclassification petition if it identifies a legally marketed predicate device that would be appropriate for a 510(k) or determines that the device is not low to moderate risk or that general controls would be inadequate to control the risks and special controls cannot be developed.

Premarket Approval Pathway

Pre-market Approval Pathway

A PMA application must be submitted to the FDA for Class 3 devices for which the FDA has required a PMA.

The PMA application process is much more demanding than the 510(k) premarket notification process.

The PMA application process is much more demanding than the 510(k) pre-market notification process.

A PMA application must be supported by extensive data, including but not limited to technical, preclinical, clinical trials, manufacturing and labeling to demonstrate to the FDA’s satisfaction reasonable evidence of safety and effectiveness of the device.

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After a PMA application is submitted, the FDA has 45 days to determine whether the application is sufficiently complete to permit a substantive review and thus whether the FDA will file the application for review.

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Although the FDA is not bound by the advisory panel decision, the panel’s recommendations are important to the FDA’s overall decision-making process.

In addition, the FDA may conduct a preapproval inspection of the manufacturing facility to ensure compliance with the QSR.

In addition, the FDA may conduct a preapproval inspection of the manufacturing facility to ensure compliance with the QMSR that went into effect in February 2026, replacing the former QSR.

The agency also may inspect one or more clinical sites to assure compliance with FDA’s regulations.

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• establishment registration and device listing;

• the QSR, which requires manufacturers, including third-party manufacturers, to follow stringent design, testing, control, documentation, and other quality assurance procedures during all aspects of the manufacturing process;

• the QMSR, which requires manufacturers, including third-party manufacturers, to follow stringent design, testing, control, documentation, and other quality assurance procedures during all aspects of the manufacturing process;

• labeling regulations and the FDA prohibitions against the promotion of products for uncleared, unapproved or off-label uses and other requirements related to promotional activities;

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• medical device reporting regulations, which require that manufactures report to the FDA if their device may have caused or contributed to a death or serious injury, or if their device malfunctioned and the device or a similar device marketed by the manufacturer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur;

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Additionally, some states require us to register as a medical device manufacturer within the state.

Because of this, the FDA and similar state agencies may inspect us on a routine basis for compliance with the QSR.

In February 2024, the FDA issued a final rule replacing the QSR with the QMSR, which incorporates by reference the quality management system requirements of ISO 13485:2016.

The FDA has stated that the standards contained in ISO 13485:2016 are substantially similar to those set forth in the existing QSR.

This final rule does not go into effect until February 2026.

Because of this, the FDA and similar state agencies may inspect us on a routine basis for compliance with the QMSR, which incorporates by reference the quality management system requirements of ISO 13458:2016.

These regulations require that the manufacturer maintain proper documentation in a prescribed manner with respect to manufacturing, testing and control activities.

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The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability, including substantial monetary penalties and criminal prosecution.

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Newly discovered or developed safety or effectiveness data may require changes to a product’s labeling, including the addition of new warnings and contraindications, and also may require the implementation of other risk management measures.

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If any such changes were imposed, they could adversely affect the operation of our business.

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The AKS prohibits, among other things, the knowing and willing, direct or indirect offer, receipt, solicitation, or payment of remuneration in exchange for or to induce the referral of patients, including the purchase, order or lease of any good, facility, item or service that would be paid for in whole or part by Medicare, Medicaid or other federal health care programs.

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Effective January 1, 2022, these reporting obligations with respect to covered recipients have been extended to include payments and transfers of value made

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to non-physician providers such as physician assistants and nurse practitioners.

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Third-party payors include state and federal government health care programs, managed care providers, private health insurers and other organizations.

Although we currently believe that third-party payors will provide coverage and reimbursement for our product candidates, if approved, we cannot be certain of this.

Although we currently believe that third-party payors will provide coverage and reimbursement for our approved product and product candidates, if approved, we cannot be certain of this.

Third-party payors are increasingly challenging the price, examining the cost-effectiveness, and reducing reimbursement for medical products and services.

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Significant uncertainty exists as to the reimbursement status of newly approved healthcare products.

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government, state legislatures and foreign governments have continued implementing cost containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products.

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These new laws may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on customers for our product candidates, if approved, and, accordingly, our financial operations.

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Under the American Rescue Plan Act of 2021, the statutory cap on Medicaid Drug Rebate Program rebates that manufacturers pay to state Medicaid programs was eliminated.

Elimination of this cap may require pharmaceutical manufacturers to pay more in rebates than they receive on the sale of products, which could have a material impact on our business.

Further, in July 2021, an executive order, “Promoting Competition in the American Economy,” was released with multiple provisions aimed at increasing competition for prescription drugs.

In August 2022, Congress passed the IRA, which includes prescription drug provisions that have significant implications for the pharmaceutical industry and Medicare beneficiaries, including allowing the federal government to negotiate a maximum fair price for certain high-priced single source Medicare drugs, imposing penalties and excise tax for manufacturers that fail to comply with the drug price negotiation requirements, requiring inflation rebates for all Medicare Part B and Part D drugs, with limited exceptions, if their drug prices increase faster than inflation, and redesigning Medicare Part D to reduce out-of-pocket prescription drug costs for beneficiaries, among other changes.

Further, in August 2022, Congress passed the IRA, which includes prescription drug provisions that have significant implications for the pharmaceutical industry and Medicare beneficiaries, including allowing the federal government to negotiate a maximum fair price for certain high-priced single source Medicare drugs, imposing penalties and excise tax for manufacturers that fail to comply with the drug price negotiation requirements, requiring inflation rebates for all Medicare Part B and Part D drugs, with limited exceptions, if their drug prices increase faster than inflation, and redesigning Medicare Part D to reduce out-of-pocket prescription drug costs for beneficiaries, among other changes.

Various industry stakeholders have initiated lawsuits against the U.S.

government asserting that the price negotiation provisions of the IRA are unconstitutional.

The impact of these judicial challenges, legislative, executive, and administrative actions and any future healthcare measures and agency rules on us and the pharmaceutical industry as a whole is unclear.

Further, the current administration has issued executive orders focused on decreasing prescription drug prices, including directing the Secretary of HHS to establish a mechanism through which American patients can buy drugs directly from manufacturers who sell at an MFN price and directing the U.S.

Trade Representative and Secretary of Commerce to take action to ensure foreign countries are not engaged in practices that purposefully and unfairly undercut market prices and drive price hikes in the U.S.

In November 2025, CMS announced a voluntary initiative called the GENEROUS Model (GENErating cost Reductions fOr U.S.

Medicaid Model) to introduce the option of MFN pricing to the Medicaid program, whereby a drug manufacturer may voluntarily offer supplemental rebates to participating state Medicaid programs for a manufacturer’s covered outpatient drugs.

Government agreements with pharmaceutical companies and other measures that use MFN pricing targets for prescription drugs or that increase generic and biosimilar drug entry sooner than expected can have a material adverse effect on our industry, ability to set adequate pricing for new drugs to recover research and development costs, ability to attract potential investors and potential buyers in the future, or the pricing of our approved product in the U.S.

and in foreign countries.

The impact of any future healthcare measures and agency rules on us and the pharmaceutical industry as a whole is unclear.

The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our product candidates if approved.

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Foreign Regulation

In addition to regulations in the U.S., we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our product candidates to the extent we choose to develop or sell any product candidates outside of the U.S.

Now that we have received approval by the UK MHRA and the Saudi Arabia SFDA and have been granted conditional marketing authorization from the EC (EMA) for the EU and Iceland, Liechtenstein, and Norway, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of ANKTIVA and our product candidates to the extent we choose to develop or sell any product candidates outside the U.S.

The approval process varies from country to country and the time may be longer or shorter than that required to obtain FDA approval.

The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country.

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HUMAN CAPITAL

ImmunityBio’s success is driven by a highly skilled workforce that designs, develops, and commercializes innovative cell and immunotherapy products to help strengthen each patient’s natural immune system, potentially enabling it to outsmart the disease and eliminate cancerous or infected cells.

Our Human Resources talent strategy relies on attracting, retaining and developing top talent that align with our culture and mission to “Outsmart Your Disease.” We promote a culture that is focused on delivering treatments utilizing natural immunities, and we seek to harness our science first focus to deliver solutions to patients and families.

As of December 31, 2024, we had 680 employees located across the U.S.

Among our employees, 41% are focused on research and development, 26% on manufacturing and quality, and 33% on selling, general and administrative functions.

We have not been subject to labor action or union activities, and our management considers its relationship with employees to be good.

We believe that fostering a workplace that celebrates differences and strengths creates an environment that supports the inclusion and value of diverse thoughts, backgrounds and perspectives.

A well-rounded culture allows for ongoing dialogue and discussions that challenge the status quo and create a learning environment that supports diversity, equity and inclusion.

As part of our commitment, we continue to encourage a culture where employees can freely ask questions and raise concerns.

Our annual performance review process helps support our commitment to develop and retain top talent by providing an opportunity to have open dialogue, establish goals, discuss milestones and continue to engage in opportunities to develop and cultivate the talent.

Additionally, we conduct an annual employee engagement survey, and our management team makes themselves available to all employees, including 1:1s, Department Meetings and Town Hall events.

Our ongoing success will continue to depend on our ability to attract, engage and retain top talent in an ever growing competitive market.

We offer a competitive compensation package to help meet the needs of our employees, incentivize performance and enhance retention.

In addition to salaries, these programs include the potential to receive annual bonuses and equity awards, and a 401(k) plan, healthcare and insurance benefits, flexible spending accounts, paid time off, family leave, flexible work schedules, and an employee assistance program, among others.

We work to ensure pay equity by assessing our compensation practices and working with external benchmarks and compensation consultants to design and benchmark our programs.

Patrick Soon-Shiong, Executive Chairman and Global Chief Scientific and Medical Officer

Soon-Shiong is a physician-scientist, inventor, and philanthropist who has spent more than 30 years developing treatments for cancer and other diseases.

He is the inventor of Abraxane, an FDA-approved chemotherapy that has treated hundreds of thousands of cancer patients worldwide.

Soon-Shiong holds over 400 issued patents.

His focus on restoring immune competence has guided the development of the company’s Cancer BioShield platform.

Richard Adcock, President and Chief Executive Officer

Adcock has held leadership roles in healthcare for nearly 30 years and is recognized for his expertise in building cultures that drive rapid, strategic innovation.

He is a certified Six Sigma Master Black Belt.

Before joining ImmunityBio, Mr.

Adcock served as CEO of Verity Health System and as Executive Vice President and Chief Innovation Officer for Sanford Health, the largest rural nonprofit healthcare system in the U.S.

with more than 382 locations and 28,000 employees.

Employee Headcount and Composition

As of December 31, 2025, ImmunityBio employed 691 employees, of which 41% are focused on research and development, 25% on manufacturing and quality, and 34% on selling, general and administrative functions.

• Full‑time/part‑time:

99% of the workforce is full‑time

• Geographic distribution:

The majority of our employees are located in our Southern California facilities, with others in our facilities in Washington, Colorado, New Jersey, and New York.

Approximately 40% of our workforce is remote.

ImmunityBio is committed to building a workplace that values diversity in thought and perspective and that reflects the patient populations we serve.

approximately 50%/50% male/female

approximately 41% white;

and the remainder declined to report

Talent Development, Attraction, and Retention

Our ability to attract and retain top talent is essential to our strategy.

Additionally, we conduct regular employee engagement surveys, and our management team makes themselves available to all employees, including 1:1s, Department Meetings and Town Hall events.

• Career development:

We provide opportunities to move throughout the organization via multiple career frameworks such as scientific, manufacturing, and operations tracks.

• Retention :

The voluntary turnover rate was 7.4% for the fiscal year ended 2025, which is less than industry benchmarks.

• Well‑being initiatives:

Employees have access to wellness programs and mental‑health resources to ensure well-rounded care and opportunities are easily available.

Compensation and Benefits

Compensation is designed to attract, motivate, and retain talent while aligning employee interests with shareholder value.

• Compensation methodology:

Utilizes benchmark data to ensure market competitiveness, in addition to a focus on pay for performance.

• Incentive awards:

Employees are eligible for annual cash bonuses and new hire equity and potential long‑term discretionary equity awards that vest over 3 years.

We offer comprehensive health, dental, vision, and retirement plans, as well as supplemental programs such as voluntary life, accident and pet insurance.

ORGANIZATION AND DEVELOPMENT OF IMMUNITYBIO, INC.

1 unchanged sentence

is incorporated in Delaware and its principal executive offices are located in San Diego, California.

The company operates in one business and one reportable segment.

The company operates in one operating and one reportable segment.

ImmunityBio, Inc.

7 unchanged sentences

We have included the web addresses of ImmunityBio and the SEC as inactive textual references only.

Except as specifically incorporated by reference into this Annual Report, information on these websites, including the higher resolution images referred to in the “Founder’s Vision” section of this Annual Report, is not part of this filing.

Table of Conten t s

Except as specifically incorporated by reference into this Annual Report, information on these websites is not part of this filing.

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