ImmunityBio, Inc. (IBRX) Business

ITEM 1.     BUSINESS.

Forward-Looking Statements

This Annual Report contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Exchange Act that are based on our management’s beliefs and assumptions and on information currently available to our management. Forward-looking statements include, but are not limited to:

•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 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;

•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;

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•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 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;

•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 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 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;

•our belief regarding the magnitude or duration for additional clinical testing of our cytokine fusion proteins, DNA or recombinant protein vaccines, or cell therapies, along with other product candidate families;

•even if we successfully develop and commercialize specific product candidates, our ability to develop and commercialize our other product candidates either alone or in combination with other therapeutic agents;

•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;

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

•our ability to attract and retain key personnel;

•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 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 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; and

•regulatory developments in the U.S. and foreign countries.

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. and the negatives of those terms. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. Statements of past performance, efforts, or results of our preclinical and clinical trials, about which inferences or assumptions may be made, can also be forward-looking statements and are not indicative of future performance or results. These statements are based upon information available to us as of the date of this Annual Report, and although we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted a thorough inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain, and investors are cautioned not to unduly rely upon these statements.

This Annual Report also contains estimates, projections and other information concerning our industry, our business, and the markets for certain diseases, including data regarding the estimated size of those markets, and the incidence and prevalence of certain medical conditions. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. Unless otherwise expressly stated, we obtained this industry, business, market, and other data from reports, research surveys, studies, and similar data prepared by market research firms and other third parties, industry, medical and general publications, government data, and similar sources.

Forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. We discuss these risks in greater detail in Item 1A. “Risk Factors” of this Annual Report. Given these uncertainties, you should not place undue reliance on these forward-looking statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame. Also, forward-looking statements represent our management’s beliefs and assumptions only as of the date of this Annual Report.

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Except as required by law, we assume no obligation to update these forward-looking statements, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future. 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, 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, 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.

This Annual Report contains references to our products and trademarks and products and trademarks belonging to other entities. Solely for convenience, trademarks and trade names referred to in this Annual Report, including logos, artwork, and other visual displays, may appear without the ® or TM symbols, but such references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. 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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BUSINESS

OVERVIEW

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;

•Prostate cancer; and

•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.

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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:

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

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.

Prevalence: 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.”

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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

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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

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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.”

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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.

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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.

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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.

Conclusion: 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.

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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.

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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:

1.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.

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

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

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

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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. See Item 1A. “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.

OUR STRATEGY

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; and

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

ANKTIVA: 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.

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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.

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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

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 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

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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 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 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

We have developed and/or acquired rights to multiple vaccine delivery technologies for oncology to deliver common TAAs, and neoepitopes (expressed only by cancer cells) and for infectious diseases to target key viruses. 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 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 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 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 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.

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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. M-ceNK cells are further distinguished by their unique cell-surface marker profile and their highly desirable feature of immune-memory, marked by their pronounced anti-cancer activity for weeks to months in duration, which has made these cells a research focus for more than a decade. We have developed a unique ability to generate a portfolio of distinct M-ceNK cell products through the application of our proprietary technology and cytokines. 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.

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: 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)

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•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

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 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.

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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; 95% CI: 59.6%, 80.3%)

•Median Duration of Complete Response: 26.6 months (95% CI: 9.9, upper bound not reached)

•24-Month Cystectomy Avoidance: 91.4% in patients with complete response; 84.1% in all patients

•24-Month Disease-Specific Survival: 100%

•Safety: 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.

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

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.

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: 83.1%

•12-Month Cystectomy-Free Survival: 92.2%

•36-Month Cystectomy-Free Survival: 81.8%

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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. 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.

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.

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.

Enrollment: 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.

Timeline: 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.

Lung Cancer

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.

QUILT-3.055: 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.

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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: 11.7, 17.4)

•Published Historical Comparator (any therapy post-CPI, Freeman et al., 2020): 6.1 months

•Published Historical Comparator (docetaxel + CYRAMZA, Brueckl et al., 2021): 7.5 months

•Maximum overall survival: 58 months

•Patients achieving ALC =1.2 x 10³ cells/µL: 80% (69/86)

•Median overall survival in patients with ALC =1.2 x 10³ cells/µL : 15.8 months (95% CI: 12.6, 21.9)

•Median overall survival in patients with ALC 1.2 : 11.5 months (95% CI: 4.2, 13.3); p=0.0057

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

QUILT-2.023: 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; p=0.0369)

•Patients achieving ALC =1.2 x 10³ cells/µL: median OS 21.1 months (hazard ratio 0.33; p=0.0009)

•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.

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ResQ201A: 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.

Enrollment: 462 patients randomized 2:1. Experimental arm (N=308): ANKTIVA in combination with TEVIMBRA. Control arm (N=154): Docetaxel. Participant randomization to either the experimental or control arm will be stratified by geographical region (North America vs. Europe vs. Asia), NSCLC histology (squamous vs. nonsquamous), and actionable genomic alterations.

Partnership: January 2025 collaboration with BeOne.

Timeline: 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. in 2026. 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; 95% CI: 0.26, 0.80)

•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.

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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

Enrollment: 20 participants at U.S. sites

Agents: ANKTIVA + iNKT

Status: 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. in 2026. 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%.

QUILT-3.078: 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)

Enrollment: 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 (p0.001, 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

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Next Steps: 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.

QUILT-106: 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).

Enrollment: 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

Case Report: 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:

ResQ215A: Relapsed Refractory NHL

Trial Design: Single arm trial lymphodepletion

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

Status: Enrolling

ResQ215B: Indolent Non-Hodgkin Lymphoma (Including Waldenström)

Trial Design: Single arm trial, no lymphodepletion

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

Status: Submitted

Planned Randomized Trial Relapsed/Refractory NHL

Trial Design: Randomized lymphodepletion

Agents:

•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)

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%.

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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; 95% CI: 0.26, 0.80)

•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.

Enrollment: 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.

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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.

Enrollment: Up to 18 patients

Results: 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

According to the American Cancer Society, one in eight men will be diagnosed with prostate cancer with an estimated 333,830 new diagnoses in 2026. Prostate cancer is the second leading cause of cancer death in men with 36,320 deaths expected in 2026.

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.

Agents: 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.

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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

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.

Trials:

•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: Phase 2 trial (N=14) investigating ANKTIVA during acute HIV infection. Trial completed, data analyses ongoing.

Long COVID

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.

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MANUFACTURING AND DISTRIBUTION

We have adopted a strategic position to be vertically-integrated and are committed to the goal of developing our products in compliance with the FDA’s GMP standards for large-scale manufacturing, even during Phase 2 clinical trial development. Biological upstream and downstream manufacturing capabilities, with their attendant know-how and regulatory compliance for approval, have long lead times. We have adopted an approach for preparedness to provide our vaccine, immunotherapy, and cell therapy products at a global scale. As such, we have established our own plants and have access to facilities on a global basis.

Our ability to create an efficient manufacturing process and supply chain will be important in enabling us to develop novel therapies. Our strategy is to anticipate the needs of our early-stage research and development initiatives for preclinical and eventual clinical product candidates with a focus on rapid capability to produce at scale fusion proteins, hAd5, protein subunits, toll receptor activators, and NK cell products. We believe members of our management team, many of whom have experience in both nanoparticle commercialization and large-scale injectable drug production, are capable of constructing the processes and commissioning the facilities necessary to meet our development and commercialization goals. For well-known processes, we currently work and plan to continue working with established third-party CMOs to produce drug substance and drug products. In addition, we plan to further enhance our in-house manufacturing capabilities for drug substance, drug products, and labeling and packaging.

Overview of our Manufacturing Model

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

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. While we believe the overall experience of these multi-national biologics manufacturers is important, the work they perform for us may involve only one of their facilities. 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.

Clinical Trial GMP Antibody and Fusion Protein Production

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

We have established other facilities for adenovirus production in multiple sites in California and a site in Colorado for oncology and infectious diseases. We are committed to the goal of complying with cGMP at these facilities. We believe we possess adequate inventory to supply our ongoing adenovirus-related clinical trial activities for the foreseeable future. We may determine to outsource manufacturing to a third-party CMO beyond the clinical phase. These facilities generally have fully-integrated biologic upstream and downstream production suites and quality assurance/quality control release laboratories for high capacity, continuous, or personalized just-in-time vaccine production.

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Clinical Trial GMP NK Cell Therapy Production

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

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. See Item 1A. “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

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.

COMPETITION

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.

Competitive Landscape by Indication

NMIBC

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.

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NSCLC

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.

Cell Therapy

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

We strive to protect and enhance the proprietary technology, inventions, and improvements that are commercially important to our business, including seeking, maintaining, and defending patent rights, whether developed internally or licensed from third parties. Our policy is to seek to protect our proprietary position by, among other methods, filing patent applications in the U.S. and in jurisdictions outside of the U.S. related to our proprietary technology, inventions, improvements, and product candidates that are important to the development and implementation of our business. We also rely on trade secrets and know-how relating to our proprietary technology and product candidates, continuing innovation, and in-licensing opportunities to develop, strengthen, and maintain our proprietary position in the field of cancer therapeutics and immunotherapy. We expect to rely on data exclusivity, market exclusivity, patent term adjustment and patent term extensions when available, as well as on regulatory protection afforded through orphan drug designations. Our commercial success will depend in part on our ability to obtain and maintain patent and other proprietary protection for our product candidates, technology, inventions, and improvements; to preserve the confidentiality of our trade secrets; to maintain our licenses to use intellectual property owned by third parties; to defend and enforce our proprietary rights, including our patents; and to operate without infringing, misappropriating or otherwise violating the valid and enforceable patents and other proprietary rights of third parties.

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-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.

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As of December 31, 2025, we own patents and patent applications related to the development and commercialization of N-803 in the U.S. and jurisdictions outside of the U.S. Our owned patent portfolio is directed to compositions of matter of N-803, methods of use of N-803, and combinations with additional therapeutics. Excluding any patent term adjustment and patent term extension, the issued U.S. patents directed to N-803 are expected to expire from 2028 to 2040. If patents issue from our pending U.S. patent applications, excluding any patent term adjustment and patent term extension, such patents will be expected to expire from 2031 to 2045. For example, these patents and patent applications include claims directed to:

•compositions of matter of N-803;

•uses of N-803 in methods of treating cancers;

•uses of N-803 in treating HIV; and

•combination treatments using N-803 and additional therapeutics.

In June 2024, we submitted applications to the USPTO for the extension of the patent term of several U.S. patents directed to compositions of matter of N-803, methods of use of N-803 and methods of manufacture of N-803. These applications are currently under review by the USPTO and FDA.

As of December 31, 2025, we own, co-own, and in-license patents and patent applications related to the development and commercialization of cell-based therapies in the U.S. and jurisdictions outside of the U.S. Our owned, co-owned, and in-licensed patent portfolio is directed to compositions of matter of NK, haNK, and t-haNK cell lines, methods of use of these cells, and combinations with additional therapeutics. Excluding any patent term adjustment and patent term extension, the issued U.S. patents directed to these cell therapies, methods of use, and combinations with additional therapeutics are expected to expire from 2034 to 2040. If patents issue from our pending U.S. patent applications, excluding any patent term adjustment and patent term extension, such patents will be expected to expire from 2034 to 2045. For example, these patents and patent applications include claims directed to:

•NK cells;

•haNK cells;

•EGFR NK-CAR;

•CD19 NK-CAR;

•HER2 NK-CAR; and

•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. and jurisdictions outside of the U.S. Our owned patent portfolio is directed to compositions of matter and methods of use of these fusion proteins. Excluding any patent term adjustment and patent term extension, the issued U.S. patents directed to these fusion proteins are expected to expire from 2028 to 2039. If patents issue from our pending U.S. patent applications, excluding any patent term adjustment and patent term extension, these patents will be expected to expire from 2028 to 2044. For example, these patents and patent applications include claims directed to fusions of CPI and TAA binding antibodies and binding molecules with IL-15/IL-15Rα/Fc fusion proteins complexes.

As of December 31, 2025, we own patents and patent applications related to development and commercialization of multi-functional cytokine fusion proteins targeting TGF-ß, the IL-15 pathway, the IL-21 pathway, and CD16 in the U.S. and jurisdictions outside of the U.S. Our owned patent portfolio is directed to compositions of matter and methods of use of these fusion proteins. Excluding any patent term adjustment and patent term extension, the issued U.S. patents directed to these fusion proteins are expected to expire from 2039 to 2041. If patents issue from our pending U.S. patent applications, excluding any patent term adjustment and patent term extension, these patents will be expected to expire from 2039 to 2045. 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. and jurisdictions outside of the U.S. Our patent portfolio is directed to compositions of matter of adenovirus and methods of use of adenovirus in treating or preventing cancer and viral diseases. Excluding any patent term adjustment and patent term extension, the issued U.S. patents directed to adenovirus-based cancer and viral immunotherapies are expected to expire from 2028 to 2044. If patents issue from our pending U.S. patent applications, excluding any patent term adjustment and patent term extension, such patents will be expected to expire from 2030 to 2044. For example, these patents and patent applications include claims directed to:

•adenovirus vectors and virus particles comprising TAAs; and

•uses of adenovirus vectors and virus particles in methods of treating cancers.

As of December 31, 2025, we own U.S. patents and pending U.S. patent applications directed to therapeutics for COVID-19. Some of these patent applications are directed to the use of our adenovirus technologies for a COVID-19 vaccine. Excluding any patent term adjustment and patent term extension, the issued U.S. patents directed to therapeutics for COVID-19 are expected to expire in 2040 and 2042. If any patents issue from our pending U.S. patent applications, excluding any patent term adjustment and patent term extension, such patents will be expected to expire in 2040 and 2045.

As of December 31, 2025, we own patents and patent applications related to the development and commercialization of GMP-in-a-Box in the U.S. and jurisdictions outside of the U.S. Our patent portfolio is directed to GMP-in-a-Box. Excluding any patent term adjustment and patent term extension, the issued U.S. patents directed to GMP-in-a-Box are expected to expire from 2030 to 2037. For example, these patents and patent applications include claims directed to methods, bioreactors, and apparatuses for monitoring and culturing cells.

The terms of individual patents extend for varying periods of time, depending upon the date of filing of the patent application, the date of patent issuance, and the legal term of patents in the countries in which they are obtained. Generally, patents issued for applications filed in the U.S. are effective for 20 years from the earliest effective filing date of a non-provisional patent application. The patent term may be adjusted to compensate for delayed patent issuance when such delays are caused by the USPTO or successful appeals against USPTO actions. There is no statutory limit on this patent term adjustment, which is generally the length of any such delays caused by the USPTO. In addition, in certain instances, a patent term can be extended to recapture a portion of the term effectively lost as a result of the FDA regulatory review period. The restoration period cannot be longer than five years, the total patent term, including the restoration period, must not exceed 14 years following FDA approval, only one patent applicable to an approved drug may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended. While we are seeking such patent term extensions where applicable, there is no guarantee that the USPTO and/or FDA will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions. While we plan to seek such patent term adjustments where applicable, there is no guarantee that the USPTO will agree with our assessment of whether such adjustments should be granted, and if granted, the length of such adjustments. The duration of patents outside of the U.S. varies in accordance with provisions of applicable local law but typically is also 20 years from the earliest effective filing date. However, the actual protection afforded by a patent varies on a product-by-product and country-to-country basis and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country, and the validity and enforceability of the patent.

The patent positions of companies like ours are generally uncertain and involve complex legal and factual questions. No consistent policy regarding the scope of claims allowable in patents in the field of immunotherapy has emerged in the U.S. The patent situation outside of the U.S. is even more uncertain. Changes in either the patent laws or their interpretation in the U.S. and other countries may diminish our ability to protect our inventions and enforce our intellectual property rights, and more generally could affect the value of our intellectual property. 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. 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

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candidates. 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. Our issued patents and those that may issue in the future may be challenged, invalidated, or circumvented, which could limit our ability to stop competitors from marketing related products or limit the length of the term of patent protection that we may have for our approved product and other product candidates. In addition, the rights granted under any issued patents may not provide us with protection or competitive advantages against competitors with similar technology. Furthermore, our competitors may independently develop similar technologies. For these reasons, we may have competition for our approved product and other product candidates. Moreover, because of the extensive time required for development, testing and regulatory review of a potential product candidate, it is possible that, before any particular product candidate can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby reducing any advantage of the patent.

Our registered trademark portfolio currently contains registered trademarks in the U.S. and in foreign jurisdictions and pending trademark applications in the U.S. and in foreign jurisdictions. We may also rely, in some circumstances, on trade secrets to protect our technology. However, trade secrets are difficult to protect. We seek to protect our trade secrets and other proprietary information, in part, by entering into confidentiality agreements with those who have access to our confidential information, including our employees, contractors, consultants, collaborators, and advisors. We also seek to preserve the integrity and confidentiality of our proprietary technology and processes by maintaining physical security of our premises and physical and electronic security of our information technology systems. Although we have confidence in these individuals, organizations, and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become known or may be independently discovered by competitors. To the extent that our employees, contractors, consultants, collaborators, or advisors use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions. See Item 1A. “Risk Factors—Risks Related to Intellectual Property” and Item 3. “Legal Proceedings” of this Annual Report for risks related to our proprietary technology, inventions, improvements, and products.

COLLABORATION AND LICENSE AGREEMENTS

We anticipate that strategic collaborations will continue to be an integral part of our operations, providing opportunities to leverage our partners’ expertise and capabilities to gain access to new technologies and further expand the potential of our technologies and product candidates across relevant platforms. We believe we are well positioned to become a leader in immunotherapy due to our broad and vertically-integrated platforms and through complementary strategic partnerships. Agreements shown below have been arranged in alphabetical order.

The following description of certain of our collaboration and license agreements is not a comprehensive listing of all such agreements to which we are a party, and the inclusion of a description of any collaboration or license agreement is not an indication that we consider such agreement(s) to be material to our business and operations as a whole, which is a dynamic and evolving analysis and may change over time.

Collaboration Agreements

National Cancer Institute

The company and its subsidiaries began their relationship with HHS, as represented by the NCI of the NIH in 2015. Pursuant to the CRADAs, the NCI provides scientific staff and other support necessary to conduct research and related activities as described in the CRADAs. During the term of the initial and amended CRADAs, we collaborated with the NCI on the preclinical and clinical development of our proprietary adenovirus technology expressing TAAs for cancer immunotherapy.

In 2021, the CRADA was amended and the research plan was modified to include the preclinical and clinical development of ImmunityBio’s proprietary adenovirus platform expressing TAAs, proprietary agent ANKTIVA and derivatives, an antibody-based cytokine fusion protein and derivatives and/or TxM product candidates, proprietary recombinant NK cells and mAbs, proprietary adjuvants, and other proprietary agents owned or controlled by ImmunityBio for cancer immunotherapy. The term of the CRADA was extended through May 2026. 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. 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. 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 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. 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.

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.

License Agreements

3M IPC License Agreement

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 superagonist. Adjuvants are either synthetic or naturally occurring molecules that activate TLRs thereby enhancing the humoral and cell-mediated immune response of vaccines. There are 10 human TLRs expressed either on the inside or outside of the immune cell and their function is to recognize foreign substances expressed by pathogens. Once activated, these TLRs stimulate danger signals to the immune cells initiating an immune response. The synthetic imidazoquinolinone 3M-052 is structurally similar to resiquimod. 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. We have also agreed to make payments upon the achievement of certain regulatory milestone events and tiered royalties ranging from the low to high single-digits as a percentage of net sales. Beginning in April 2026, the annual minimum licensing payment is $1.0 million, which can be credited against any royalty payments due under this agreement. We may terminate this license for any reason after providing 3M and AAHI sixty (60) days’ written notice.

GlobeImmune, Inc.

In 2020, we entered into an exclusive licensing agreement with GlobeImmune, a consolidated entity of the company, pursuant to which we obtained worldwide, exclusive licenses under certain patents, know-how, and other intellectual property to use, research, develop and commercialize products with GlobeImmune’s Tarmogen-based programs and neoepitopes programs in exchange for a license fee for the first two years of the agreement totaling $1.2 million, up to $345.0 million in milestone payments related to the successful completion of clinical and regulatory milestones and up to $240.0 million in total milestone payments based on licensed product net sales milestones, 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. 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

In 2017, and as amended in November 2021, we entered into a license agreement with Sanford Health pursuant to which we obtained a worldwide, exclusive license under Sanford’s applicable patent and know-how rights to use, make, have made, sell, offer to sell, export and import products for all uses and applications of polynucleotides encoding mutant E16 antigen (mutant HPV16 E6 antigen + mutant HPV16 E7 antigen) and the encoded mutant E16 antigen, in exchange for consideration that includes the amount equal to the patent prosecution costs incurred by Sanford for the prosecution of the licensed patent rights, milestone payments payable upon the achievement of certain contractual and regulatory milestones of up to $2.0 million, a low single-digit percentage royalty on net sales of the resulting licensed products, and a low to high-teen percentage share of non-royalty sublicensing revenue. Our obligation to pay royalties continues, on a licensed product-by-licensed product and country-by-country basis, until the date on which such licensed product is no longer covered by a valid claim of a patent licensed pursuant to the agreement in such country. We must use commercially reasonable efforts to develop and commercialize the licensed products. Sanford is responsible for the prosecution and maintenance of the patents licensed pursuant to the agreement. We are required to use commercially reasonable efforts to develop and make available the licensed products, which include achieving certain regulatory objectives within certain specific time periods. We have the first right to enforce the patents licensed pursuant to the agreement, subject to Sanford’s ability to exercise such right if we fail to do so. We may terminate this agreement at any time upon 60 days’ written notice to Sanford. Sanford may terminate the agreement in the event of an uncured material breach by us.

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. Ltd.

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. Altor has the sole right to prosecute and maintain the patents licensed pursuant to the agreement. Altor has the first right to enforce the patents licensed pursuant to the agreement, subject to Beike’s ability to exercise such right if Altor fails to do so. Altor and Beike each have the right to terminate the agreement in the event of a material breach by the other party. In 2020, we received a Request for Arbitration before the International Chamber of Commerce, International Court of Arbitration, served by Beike asserting breach of contract under our subsidiary Altor’s license agreement with them. See Item 3. “Legal Proceedings” for more information.

GOVERNMENT REGULATION

In the U.S., the FDA regulates biopharmaceuticals under the FD&C Act and the PHSA. 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. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or post-market may subject an applicant to administrative or judicial sanctions. These sanctions could include, among other actions, the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, untitled or warning letters, product recalls or market withdrawals, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement and civil or criminal penalties. Any FDA or judicial enforcement action could have a material adverse effect on us. Failure to comply with statutory and regulatory requirements subjects a manufacturer to possible legal or regulatory action, including warning letters, the seizure or recall of products, injunctions, consent decrees placing significant restrictions on or suspending manufacturing operations and civil and criminal penalties. CMOs often encounter difficulties involving production yields, quality control and quality assurance, as well as shortages of qualified personnel. 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. We, along with third-party contractors, will be required to navigate the various preclinical, clinical, and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval or licensure of our product candidates. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local, and foreign statutes and regulations require the expenditure of substantial time and financial resources.

The process required by the FDA before biopharmaceutical product candidates may be marketed in the U.S. generally involves the following:

•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;

•approval from an independent IRB or ethics committee for each clinical site before the clinical trial is begun;

•performance of adequate and well-controlled human clinical trials to establish the safety, purity, and potency of the proposed biologic product candidate for its intended purpose;

•preparation of and submission to the FDA of a BLA or NDA, after completion of all required clinical trials;

•a determination by the FDA within 60 days of its receipt of a BLA/NDA to file the application for review;

•satisfactory completion of an FDA Advisory Committee review, if applicable;

•satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMP and to assure that the facilities, methods, and controls are adequate to preserve the product candidates’ continued safety, quality, purity and potency or efficacy, and of selected clinical investigational sites to assess compliance with GCP guidelines;

•FDA review and approval of the BLA or NDA to permit commercial marketing of the product for particular indications for use in the U.S.; and

•compliance with any post-approval requirements, including the potential requirement to implement a REMS, and the potential requirement to conduct post-approval studies.

The testing and approval process requires substantial time, effort, and financial resources, and we cannot be certain that any approvals for our product candidates will be granted on a timely basis, if at all. Prior to beginning the first clinical trial with a product candidate, we must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an IND product to humans. The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical trials. The IND also includes results of animal and in vitro studies assessing toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product; chemistry, manufacturing, and controls information; and any available human data or literature to support the use of the investigational product. An IND must become effective before human clinical trials begin. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial. In such a case, the IND may be placed on clinical hold, and the IND sponsor and FDA must resolve any outstanding concerns or questions before the clinical trial can begin. Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial. 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.

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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. Compliance with the NIH Guidelines is mandatory for investigators at institutions receiving NIH funds for research involving wild-type DNA, and many companies and other institutions not otherwise subject to the NIH Guidelines voluntarily follow them. The NIH is responsible for convening the RAC, a federal advisory committee that discusses protocols that raise novel or particularly important scientific, safety, or ethical considerations at one of its quarterly public meetings. The OBA will notify the FDA of the RAC’s decision regarding the necessity for full public review of a protocol. RAC proceedings and reports are posted to the OBA web site and may be accessed by the public. If the FDA allows the IND to proceed, but the RAC decides that full public review of the protocol is warranted, the FDA will request at the completion of its IND review that sponsors delay initiation of the protocol until after completion of the RAC review process.

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP guidelines, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments. Furthermore, an independent IRB, for each site proposing to conduct the clinical trial, must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site and must monitor the study until completed. Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy. There are also requirements governing the reporting of ongoing clinical trials and clinical trial results to public registries.

For purposes of BLA or NDA approval, human clinical trials are typically conducted in three sequential phases that may overlap:

•Phase 1. The investigational product is initially introduced into healthy human subjects and tested for safety. In the case of some products for severe or life-threatening diseases, the initial human testing is often conducted in patients.

•Phase 2. The investigational product is evaluated in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy or potency of the product for specific targeted diseases and to determine dosage tolerance, optimal dosage, and dosing schedule.

•Phase 3. Clinical trials are undertaken to further evaluate dosage, clinical efficacy or potency, and safety in an expanded patient population at geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk to benefit ratio of the product and provide an adequate basis for product labeling.

•Phase 4. Companies may voluntarily pursue additional clinical trials after a product is approved to gain more information about the product for that approved indication.

In some cases, the FDA may require an additional trial after a product is approved, and these so-called Phase 4 trials may be a condition to approval of the BLA or NDA.

Phase 1, Phase 2, and Phase 3 testing may not be completed successfully within a specified period, if at all, and there can be no assurance that the data collected will support FDA approval or licensure of the product. Concurrently with clinical trials, companies may complete additional animal studies and develop additional information about the biological characteristics of the product candidate and must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. To help reduce the risk of the introduction of adventitious agents with use of biological products, the PHSA emphasizes the importance of manufacturing control for products whose attributes cannot be precisely defined. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, must develop methods for testing the identity, strength, quality and purity of the final product, or for biologics, the safety, purity and potency. 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

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials are submitted to the FDA as part of a BLA for a biologic product candidate or an NDA for a small molecule product candidate requesting approval to market the product for one or more indications. Unless agreed to in advance with the FDA, the BLA/NDA must include all data from pertinent preclinical and clinical trials, including negative or ambiguous results, as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls, and proposed labeling, among other things. Data can come from company-sponsored clinical trials intended to test the safety and effectiveness of the use of the product or from a number of alternative sources, including studies initiated by investigators, including government agencies (e.g., NIH). The submission of a BLA/NDA requires payment of a substantial user fee to the FDA, and the sponsor of an approved BLA/NDA is subject to annual product and establishment user fees. These fees typically increase annually. A waiver of user fees may be obtained under certain limited circumstances.

Within 60 days following submission of the application, the FDA reviews a BLA/NDA to determine if it is substantially complete before the agency accepts it for filing. The FDA may refuse to file any BLA or NDA that it deems incomplete or not properly reviewable at the time of submission and may request additional information. In this event, the BLA/NDA must be resubmitted with the additional information. Once a BLA/NDA has been submitted, the FDA’s goal is to review the application within ten months after it accepts the application for filing, or, if the application relates to an unmet medical need in a serious or life-threatening indication, the FDA may review the application six months after the FDA accepts the application for filing. The review process is often significantly extended by FDA requests for additional information or clarification. The FDA reviews a BLA/NDA to determine, among other things, whether a product is safe and effective, or safe, pure, and potent for the proposed indication(s) and the facility in which it is manufactured, processed, packed or held meets standards designed to assure the product’s continued safety, purity and potency or efficacy. The FDA may convene an advisory committee to provide clinical insight on application review questions. Before approving a BLA/NDA, the FDA will typically inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities comply with cGMP requirements and are adequate to assure consistent production of the product within required specifications. If applicable, FDA regulations also require tissue establishments to register and list their human cells, tissues, and cellular and tissue-based products with the FDA and to evaluate donors through screening and testing. Additionally, before approving a BLA/NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP guidelines. If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficiencies in the submission and often will request additional testing or information. Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

The testing and approval process requires substantial time, effort, and financial resources, and each may take several years to complete. The FDA may not grant approval on a timely basis, or at all, and we may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing our product candidates. After the FDA evaluates a BLA/NDA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a CRL. An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A CRL indicates that the review cycle of the application is complete, and the application is not ready for approval. A CRL may request additional information or clarification. The FDA may delay or refuse approval of a BLA/NDA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

If regulatory approval of a product is granted, such approval may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the BLA/NDA with a REMS plan to mitigate risks, which could include medication guides, physician communication plans, or other restrictions to assure safe use, such as restricted distribution methods, patient registries, and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing regulatory standards is not maintained or if problems occur after the product reaches the marketplace. The FDA may require one or more Phase 4 post-market trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies. 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. Specifically, new drugs and biological products are eligible for Fast Track designation if they are intended to treat a serious or life-threatening condition and demonstrate the potential to address unmet medical needs for the condition. For a Fast Track product, the FDA may consider sections of the BLA/NDA for review on a rolling basis before the complete application is submitted if relevant criteria are met. A Fast Track-designated product candidate may also qualify for priority review. Priority review is granted when there is evidence that the proposed product would be a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition. If criteria are not met for priority review, the application is subject to the standard FDA review period. Priority review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.

Under the accelerated approval program, the FDA may approve a BLA/NDA on the basis of either a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. Post-marketing studies or completion of ongoing studies after marketing approval are generally required to verify the product’s clinical benefit in relationship to the surrogate endpoint or ultimate outcome in relationship to the clinical benefit. The Food and Drug Omnibus Reform Act made several changes to the FDA’s authorities and its regulatory framework, including, among other changes, reforms to the accelerated approval pathway, such as requiring the FDA to specify conditions for post-approval study requirements and setting forth procedures for the FDA to withdraw a product on an expedited basis for non-compliance with post-approval requirements.

In addition, the FDASIA established Breakthrough Therapy designation. A sponsor may seek FDA designation of its product candidate as a Breakthrough Therapy if the product candidate is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the therapy may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Sponsors may request the FDA to designate Breakthrough Therapy at the time of, or any time after, the submission of an IND, but ideally before an end-of-Phase 2 meeting with the FDA. If the FDA designates Breakthrough Therapy, it may take appropriate actions to expedite the development and review of the application, which may include holding meetings with the sponsor and the review team throughout the development of the therapy; providing timely advice to, and interactive communication with, the sponsor regarding the development of the product candidate to ensure that the development program to gather the nonclinical and clinical data necessary for approval is as efficient as practicable; involving senior managers and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review; assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development program and to serve as a scientific liaison between the review team and the sponsor; and considering alternative clinical trial designs when scientifically appropriate, which may result in smaller or more efficient clinical trials that require less time to complete and may minimize the number of patients exposed to a potentially less efficacious treatment. Breakthrough Therapy designation also allows the sponsor to file sections of the BLA/NDA for review on a rolling basis. We may seek designation as a Breakthrough Therapy for some or all of our product candidates.

The 21st Century Cures Act established an expedited review program for RMATs, which include cell and gene therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies or products. This program is intended to facilitate efficient development and expedite review of regenerative medicine therapies, which are intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition and qualify for RMAT designation. A sponsor may request that the FDA designate a product candidate as an RMAT concurrently with or at any time after submission of an IND. The FDA has 60 calendar days to determine whether the product candidate meets the criteria, including whether there is preliminary clinical evidence indicating that the product candidate has the potential to address unmet medical needs for a serious or life-threatening disease or condition. A BLA for a product candidate that has received RMAT designation may be eligible for priority review or accelerated approval through use of surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of sites. Benefits of RMAT designation also include early interactions with the FDA to discuss any potential surrogate or intermediate endpoint to be used to support accelerated approval. A product candidate with RMAT designation that is granted accelerated approval and is subject to post-approval requirements may fulfill such requirements through the submission of clinical evidence from clinical studies, patient registries, or other sources of real world evidence, such as electronic health records; the collection of larger confirmatory data sets; 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. 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 addition, the PREA requires a sponsor to conduct pediatric clinical trials for certain drugs and biological products, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration. Under PREA, original NDAs/BLAs and supplements must contain a pediatric assessment unless the sponsor has received a deferral or waiver. The required assessment must evaluate the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The sponsor or FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations. A deferral may be granted for several reasons, including a finding that the product candidate is ready for approval for use in adults before pediatric clinical trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric clinical trials begin. The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keeps a deferral current or fails to submit a request for approval of a pediatric formulation.

Orphan Drugs

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 individuals in the U.S., or a patient population greater than 200,000 individuals in the U.S. and when there is no reasonable expectation that the cost of developing and making available the drug or biologic in the U.S. will be recovered from sales in the U.S. for that drug or biologic. Orphan drug designation must be requested before submitting a BLA or NDA. After the FDA grants orphan drug designation, the generic identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

If a product that has orphan drug designation subsequently receives the first FDA approval for a particular active ingredient for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full BLA or NDA, to market the same biologic or drug product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated. Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition. Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the BLA application user fee.

A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan designation. In addition, orphan drug exclusive marketing rights in the U.S. may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Post-Approval Requirements

Any products manufactured or distributed by us pursuant to FDA approval are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record keeping, reporting of adverse experiences, periodic reporting, distribution, and advertising and promotion of the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are continuing, annual user fee requirements for any marketed products and the establishments at which such products are manufactured, as well as new application fees for supplemental applications with clinical data. Biopharmaceutical manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP, which impose certain procedural and documentation requirements upon us and any third-party manufacturers that we may decide to use. Changes to the manufacturing process are strictly regulated and, depending on the significance of the change, may require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting requirements upon us, and any third-party manufacturers, that we may decide to use. 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

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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.

In the U.S., once a drug is approved, its manufacture is subject to comprehensive and continuing regulation by the FDA. FDA regulations require that drugs be manufactured in specific facilities per the BLA or NDA approval and in accordance with cGMP. Drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance. These regulations also impose certain organizational, procedural, and documentation requirements with respect to manufacturing and quality assurance activities. BLA or NDA holders using CMOs, laboratories or packagers are responsible for the selection and monitoring of qualified firms, and, in certain circumstances, qualified suppliers to these firms. These firms and, where applicable, their suppliers are subject to inspections by the FDA at any time, and the discovery of violative conditions, including failure to conform to cGMP, could result in enforcement actions that interrupt the operation of any such facilities or the ability to distribute drugs manufactured, processed, or tested by them.

Future FDA and state inspections may identify compliance issues at our facilities or at the facilities of CMOs that may disrupt production or distribution or require substantial resources to correct. In addition, discovery of previously unknown problems with a product or the failure to comply with applicable requirements may result in restrictions on a product, manufacturer, or holder of an approved BLA or NDA, including withdrawal or recall of the product from the market or other voluntary, FDA-initiated or judicial action that could delay or prohibit further marketing.

Post-Marketing Requirements

Following approval of a new drug, a biopharmaceutical company and the approved drug are subject to continuing regulation by the FDA, including, among other things, establishment registration and drug listing, monitoring and recordkeeping activities, reporting to the applicable regulatory authorities of adverse experiences with the drug, providing the regulatory authorities with updated safety and efficacy information, drug sampling and distribution requirements, and complying with promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting drugs for uses or in patient populations that are not described in the drug’s approved labeling, limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the internet.

In the U.S., once a drug is approved, its manufacture is subject to comprehensive and continuing regulation by the FDA. FDA regulations require that drugs be manufactured in specific facilities per the NDA approval and in accordance with cGMP. We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of its drugs in accordance with cGMP regulations. cGMP regulations require among other things, quality control and quality assurance as well as the corresponding maintenance of records and documentation and the obligation to investigate and correct any deviations from cGMP.

Drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance. These regulations also impose certain organizational, procedural, and documentation requirements with respect to manufacturing and quality assurance activities. NDA holders using CMOs, laboratories or packagers are responsible for the selection and monitoring of qualified firms, and, in certain circumstances, qualified suppliers to these firms. These firms and, where applicable, their suppliers are subject to inspections by the FDA at any time, and the discovery of violative conditions, including failure to conform to cGMP, could result in enforcement actions that interrupt the operation of any such facilities or the ability to distribute drugs manufactured, processed, or tested by them. 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. The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:

•restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

•fines, warning letters or holds on post-approval clinical trials;

•refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals;

•product seizure or detention, or refusal to permit the import or export of products; or

•injunctions or the imposition of civil or criminal penalties.

The FDA closely regulates the marketing, labeling, advertising and promotion of biological or drug products. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties, and exclusion from participation in governmental health programs, like Medicare and Medicaid. Physicians may prescribe legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products. The federal government has levied large civil and criminal fines against companies for alleged improper promotion of off-label use and has enjoined companies from engaging in off-label promotion. The FDA and other regulatory agencies have also required that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA-approved labelling. Modifications or enhancements to the drug or its labeling or changes of the site or process of manufacture are often subject to the approval of the FDA and other regulators, which may or may not be received or may result in a lengthy review process.

Prescription drug advertising is subject to federal, state, and foreign regulations. In the U.S., the FDA regulates prescription drug promotion, including direct-to-consumer advertising. 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 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. The DSCSA mandates phased-in and resource-intensive obligations for pharmaceutical manufacturers, wholesale distributors, and dispensers. The law’s requirements include the quarantine and prompt investigation of a suspect product to determine if it is illegitimate and notifying trading partners and the FDA of any illegitimate product. Drug manufacturers and their collaborators are also required to place a unique product identifier on prescription drug packages.

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. Generally, if a new device has a predicate that is already on the market under a 510(k) clearance, the FDA will allow that new device to be marketed under a 510(k) clearance; otherwise, a PMA is required. Medical devices are classified into one of three classes: Class 1, Class 2, or Class 3, depending on the degree of risk associated with each medical device and the extent of control needed to provide reasonable assurance of safety and effectiveness. Class 1 devices are deemed to be low risk and are subject to the general controls of the FD&C Act, such as provisions that relate to: adulteration; misbranding; registration and listing; notification, including repair, replacement, or refund; records and reports; and good manufacturing practices. Most Class 1 devices are classified as exempt from pre-market notification under section

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510(k) of the FD&C Act and therefore may be commercially distributed without obtaining 510(k) clearance from the FDA. Class 2 devices are subject to both general controls and special controls to provide reasonable assurance of safety and effectiveness. Special controls include performance standards, post market surveillance, patient registries and guidance documents. 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. A Class 3 device cannot be marketed in the U.S. unless the FDA approves the device after submission of a PMA. 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 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 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 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. If the FDA determines that the device, or its intended use, is not substantially equivalent to a previously cleared device or use, the FDA will place the device into Class 3.

There are three types of 510(k)s: traditional; special; and abbreviated. Special 510(k)s are for devices that are modified, and the modification needs a new 510(k) but does not affect the intended use or alter the fundamental scientific technology of the device. Abbreviated 510(k)s are for devices that conform to a recognized standard. The special and abbreviated 510(k)s are intended to streamline review, and the FDA intends to process special 510(k)s within 30 days of receipt.

De Novo Classification

Medical device types that the FDA has not previously classified as Class 1, 2 or 3 are automatically classified into Class 3 regardless of the level of risk they pose. The Food and Drug Administration Modernization Act of 1997 established a new route to market for low to moderate risk medical devices that are automatically placed into Class 3 due to the absence of a predicate device, called the Request for Evaluation of Automatic Class 3 Designation (or the De Novo Classification Process).

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) 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. If the manufacturer seeks reclassification into Class 2, the manufacturer must include a draft proposal for special controls that are necessary to provide a reasonable assurance of the safety and effectiveness of the medical device. 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.

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) 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. The FDA has 180 days to review a filed PMA application, although the review of an application generally occurs over a significantly longer period of time and can take up to several years. During this review period, the FDA may request additional information or clarification of the information already provided. Also, an advisory panel of experts from outside the FDA may be convened to review and evaluate the application and provide recommendations to the FDA as to the approvability of the device.

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 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.

Upon completion of the PMA review, the FDA may: (i) approve the PMA application which authorizes commercial marketing with specific prescribing information for one or more indications, which can be more limited than those originally sought; (ii) issue an approvable letter which indicates the FDA’s belief that the PMA application is approvable and states what additional information the FDA requires or the post-approval commitments that must be agreed to prior to approval; (iii) issue a not approvable letter which outlines steps required for approval, but which are typically more onerous than those in an approvable letter, and may require additional clinical trials that are often expensive and time consuming and can delay approval for months or even years; or (iv) deny the application. If the FDA issues an approvable or not approvable letter, the applicant has 180 days to respond, after which the FDA’s review clock is reset.

Clinical trials are almost always required to support PMA and are sometimes required for 510(k) clearance. In the U.S., for significant risk devices, these trials require submission of an application for an IDE to the FDA. The IDE application must be supported by appropriate data, such as animal and laboratory testing results, showing it is safe to test the device in humans and that the testing protocol is scientifically sound. The IDE must be approved in advance by the FDA for a specific number of patients at specified trial sites. During the trial, the sponsor must comply with the FDA’s IDE requirements for investigator selection, trial monitoring, reporting and recordkeeping. The investigators must obtain patient informed consent, rigorously follow the investigational plan, and trial protocol, control the disposition of investigational devices and comply with all reporting and recordkeeping requirements. Clinical trials for significant risk devices may not begin until the IDE application is approved by the FDA and the appropriate IRBs at the clinical trial sites. An IRB is an appropriately constituted group that has been formally designated to review and monitor medical research involving subjects and which has the authority to approve, require modifications in, or disapprove research to protect the rights, safety, and welfare of human research subjects. A non-significant risk device does not require FDA approval of an IDE; however, the clinical trial must still be conducted in compliance with various requirements of FDA’s IDE regulations and be approved by an IRB at the clinical trial sites. The FDA or the IRB at each site at which a clinical trial is being performed may withdraw approval of a clinical trial at any time for various reasons, including a belief that the risks to study subjects outweigh the benefits or a failure to comply with FDA or IRB requirements. Even if a trial is completed, the results of clinical testing may not demonstrate the safety and effectiveness of the device, may be equivocal or may otherwise not be sufficient to obtain approval or clearance of the product.

Sponsors of clinical trials of devices are required to register with clinical trials.gov, a public database of clinical trial information. Information related to the device, patient population, phase of investigation, study sites and investigators and other aspects of the clinical trial is made public as part of the registration.

Ongoing Medical Device Regulation by the FDA

Even after a device receives clearance or approval and is placed on the market, numerous regulatory requirements apply. These include:

•establishment registration and device listing;

•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;

•corrections and removal reporting regulations, which require that manufacturers report to the FDA field corrections or removals if undertaken to reduce a risk to health posed by a device or to remedy a violation of the FD&C Act that may present a risk to health; and

•post market surveillance regulations, which apply to certain Class 2 or 3 devices when necessary to protect the public health or to provide additional safety and effectiveness data for the device.

After a device receives 510(k) clearance, any modification that could significantly affect its safety or effectiveness, or that would constitute a major change in its intended use, will require a new clearance or possibly a PMA. The FDA requires each manufacturer to make this determination initially, but the FDA can review any such decision and can disagree with a manufacturer’s determination. If the FDA disagrees with the determination not to seek a new 510(k) clearance, the FDA may retroactively require the manufacturer to seek 510(k) clearance or possibly a PMA. The FDA could also require the manufacturer to cease marketing and distribution and/or recall the modified device until 510(k) clearance or PMA is obtained. Also, in these circumstances, the manufacturer may be subject to significant regulatory fines and penalties.

Some changes to an approved PMA device, including changes in indications, labeling or manufacturing processes or facilities, require submission and FDA approval of a new PMA application or PMA supplement, as appropriate, before the change can be implemented. Supplements to a PMA application often require the submission of the same type of information required for an original PMA application, except that the supplement is generally limited to that information needed to support the proposed change from the device covered by the original PMA. The FDA uses the same procedures and actions in reviewing PMA supplements as it does in reviewing original PMA applications.

FDA regulations require us to register as a medical device manufacturer with the FDA. 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 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. Further, the FDA requires medical device manufacturers to comply with various FDA regulations regarding labeling.

Failure by us or by our suppliers to comply with applicable regulatory requirements can result in enforcement action by the FDA or state authorities, which may include any of the following sanctions:

•warning or untitled letters, fines, injunctions, consent decrees and civil penalties;

•customer notifications, voluntary or mandatory recall or seizure of our medical device product candidates;

•operating restrictions, partial suspension, or total shutdown of production;

•delay in processing submissions or applications for new products or modifications to existing products;

•withdrawing approvals that have already been granted; and

•criminal prosecution.

The Medical Device Reporting laws and regulations require medical device manufacturers to provide information to the FDA when they receive or otherwise become aware of information that reasonably suggests the device may have caused or contributed to a death or serious injury as well as a device malfunction that likely would cause or contribute to death or serious injury if the malfunction were to recur. In addition, the FDA prohibits an approved device from being marketed for off-label use. 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. Also, 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 clearance or approval of our medical device product candidates under development. Medical device manufacturers are also subject to other federal, state, and local laws and regulations relating to safe working conditions, and laboratory and manufacturing practices.

Other Healthcare Laws and Compliance Requirements

Manufacturing, sales, promotion, and other activities following drug approval are also subject to regulation by numerous regulatory authorities in addition to the FDA, including, in the U.S., CMS, other divisions of HHS, the Drug Enforcement Administration for controlled substances, the Consumer Product Safety Commission, the FTC, Occupational Safety and Health Administration, the Environmental Protection Agency, and state and local governments. In the U.S., sales, marketing, and scientific/educational programs must also comply with state and federal fraud and abuse laws. Pricing and rebate programs must comply with the Medicaid rebate requirements of the U.S. Omnibus Budget Reconciliation Act of 1990 and more recent requirements in the Patient Protection and Affordable Care Act as amended by the ACA. If drugs are made available to authorized users of the Federal Supply Schedule of the General Services Administration, additional laws and requirements apply. The handling of any controlled substances must comply with the U.S. Controlled Substances Act and Controlled Substances Import and Export Act. Drugs must meet applicable child-resistant packaging requirements under the U.S. Poison Prevention Packaging Act. Manufacturing, sales, promotion, and other activities are also potentially subject to federal and state consumer protection and unfair competition laws.

We are subject to numerous foreign, federal, state, and local environmental, health, and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment, and disposal of hazardous materials and wastes. In addition, our leasing and operation of real property may subject us to liability pursuant to certain U.S. environmental laws and regulations, under which current or previous owners or operators of real property and entities that disposed or arranged for the disposal of hazardous substances may be held strictly, jointly, and severally liable for the cost of investigating or remediating contamination caused by hazardous substance releases, even if they did not know of and were not responsible for the releases.

The distribution of pharmaceutical drugs is subject to additional requirements and regulations, including extensive record-keeping, licensing, storage, and security requirements intended to prevent the unauthorized sale of pharmaceutical drugs. The failure to comply with regulatory requirements subjects firms to possible legal or regulatory action. Depending on the circumstances, failure to meet applicable regulatory requirements can result in criminal prosecution, fines, or other penalties, injunctions, voluntary recall, or seizure of drugs, total or partial suspension of production, denial or withdrawal of product approvals, or refusal to allow a firm to enter into supply contracts, including government contracts. In addition, even if a firm complies with FDA and other requirements, new information regarding the safety or efficacy of a product could lead the FDA to modify or withdraw product approval. Prohibitions or restrictions on sales or withdrawal of future products marketed by us could materially affect our business in an adverse way.

Changes in regulations, statutes, or the interpretation of existing regulations could impact our business in the future by requiring, for example: (i) changes to our manufacturing arrangements; (ii) additions or modifications to product labeling; (iii) the recall or discontinuation of our products; or (iv) additional record-keeping requirements. If any such changes were imposed, they could adversely affect the operation of our business.

Our sales, promotion, medical education, clinical research, and other activities following product approval will be subject to regulation by numerous regulatory and law enforcement authorities in the U.S. in addition to the FDA, including potentially the FTC, the Department of Justice, the CMS, other divisions of HHS and state and local governments. Our promotional and scientific/educational programs must comply with the AKS, the FCA, physician payment transparency laws, privacy laws, security laws, and additional federal and state laws similar to the foregoing. If drugs are made available to authorized users of the Federal Supply Schedule of the General Services Administration, additional laws and requirements apply. Drugs must meet applicable child-resistant packaging requirements under the U.S. Poison Prevention Packaging Act. Manufacturing, sales, promotion, and other activities are also potentially subject to federal and state consumer protection and unfair competition laws. Changes in regulations, statutes, or the interpretation of existing regulations could impact our business in the future by requiring, for example: (i) changes to our manufacturing arrangements; (ii) additions or modifications to product labeling; (iii) the recall or discontinuation of our products; or (iv) additional record-keeping requirements. 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. Remuneration has been broadly defined to include anything of value, including cash, improper discounts, and free or reduced-price items and services. The AKS has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers, formulary managers, and beneficiaries on the other. Although there are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution, the exceptions and safe harbors are drawn narrowly. Practices that involve remuneration that may be alleged to be intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor. Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the AKS. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all its facts and circumstances. Several courts have interpreted the statute’s intent requirement to mean that if any one purpose of an arrangement involving remuneration is to induce referrals of federal healthcare covered business, the AKS has been violated. The government has enforced the AKS to reach large settlements with healthcare companies based on sham research or consulting and other financial arrangements with physicians. Further, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation. In addition, the government may assert that a claim including items or services resulting from a violation of the AKS constitutes a false or fraudulent claim for purposes of the FCA. Many states have similar laws that apply to their state health care programs, as well as private payors.

Federal false claims and false statement laws, including the FCA, impose liability on persons or entities that, among other things, knowingly present or cause to be presented claims that are false or fraudulent or not provided as claimed for payment or approval by a federal health care program. The FCA has been used to prosecute people or entities that cause the submission of claims for payment that are inaccurate or fraudulent, by, for example, providing inaccurate billing or coding information to customers, promoting a product off-label, submitting claims for services not provided as claimed, or submitting claims for services that were provided but not medically necessary. Actions under the FCA may be brought by the Attorney General, or as a qui tam action by a private individual, in the name of the government. Violations of the FCA can result in significant monetary penalties and treble damages. The federal government is using the FCA, and the accompanying threat of significant liability, in its investigation and prosecution of pharmaceutical and biotechnology companies throughout the country, for example, in connection with the promotion of products for unapproved uses and other illegal sales and marketing practices. The government has obtained multi-million and multi-billion dollar settlements under the FCA in addition to individual criminal convictions under applicable criminal statutes. In addition, certain companies that were found to be in violation of the FCA have been forced to implement extensive corrective action plans and have often become subject to consent decrees or corporate integrity agreements, restricting the manner in which they conduct their business.

The HIPAA created additional federal criminal statutes that prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors; knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services; and willfully obstructing a criminal investigation of a healthcare offense. Like the AKS, the ACA amended the intent standard for certain healthcare fraud statutes under HIPAA such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

Given the significant size of actual and potential settlements, it is expected that the government will continue to devote substantial resources to investigating healthcare providers’ and manufacturers’ compliance with applicable fraud and abuse laws. In addition, many states have similar fraud and abuse statutes or regulations that may be broader in scope and may apply regardless of payor, in addition to items and services reimbursed under Medicaid and other state programs. Additionally, to the extent that our product candidates, once commercialized, are sold in a foreign country, we may be subject to similar foreign laws.

In addition, there has been a recent trend of increased federal and state regulation of payments made to physicians and certain other healthcare providers and teaching hospitals. The ACA, among other things, under the federal Physician Payment Sunshine Act, imposed reporting requirements on certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, for payments or other transfers of value made by them to certain covered recipients, including physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members. 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. Covered manufacturers are required to collect and report detailed payment data and submit legal attestation to the accuracy of such data to the government each year. Failure to submit required information may result in civil monetary penalties for all payments, transfers of value or ownership or investment interests that are not timely, accurately, and completely reported in an annual submission. Additionally, entities that do not comply with mandatory reporting requirements may be subject to a corporate integrity agreement. Certain states also mandate implementation of commercial compliance programs, impose restrictions on covered manufacturers’ marketing practices and/or require the tracking and reporting of gifts, compensation and other remuneration to physicians and other healthcare professionals.

We may also be subject to data privacy and security regulation by both the federal government and the states in which we conduct our business. HIPAA, as amended by HITECH and their respective implementing regulations, impose specified requirements on certain health care providers, plans, and clearinghouses, or collectively, covered entities, and their business associates, relating to the privacy, security and transmission of individually identifiable health information. Among other things, HITECH makes HIPAA’s security standards directly applicable to business associates, which includes independent contractors or agents of covered entities that create, receive, maintain, or transmit protected health information in connection with providing a service for or on behalf of a covered entity. HITECH also increased the civil and criminal penalties that may be imposed against covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorney’s fees and costs associated with pursuing federal civil actions. In addition, certain states have their own laws that govern the privacy and security of health information in certain circumstances, many of which differ from each other and/or HIPAA in significant ways and may not have the same effect, thus complicating compliance efforts.

If our operations are found to be in violation of any of such laws or any other governmental regulations that apply to us, we may be subject to penalties, including, without limitation, civil and criminal penalties, damages, fines, disgorgement, the curtailment or restructuring of our operations, exclusion from participation in federal and state healthcare programs, imprisonment, contractual damages, reputational harm, and diminished profits and future earnings, any of which could adversely affect our ability to operate our business and our financial results. If any of the physicians or other providers, independent contractors, or entities with whom we do business are found to not be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs and imprisonment, which could affect our ability to operate our business. Further, defending against any such actions can be costly, time-consuming and may require significant personnel resources. Therefore, even if we are successful in defending ourselves against any such actions that may be brought against us, our business may be impaired.

In addition to the foregoing health care laws, we are also subject to the FCPA and similar worldwide anti-bribery laws, which generally prohibit companies and their intermediaries from making improper payments to government officials or private-sector recipients for the purpose of obtaining or retaining business. The anti-corruption policy mandates compliance with the FCPA and similar anti-bribery laws applicable to our business throughout the world. However, we cannot assure you that such a policy or procedures implemented to enforce such a policy will protect us from intentional, reckless, or negligent acts committed by our employees, distributors, partners, collaborators or agents. Violations of these laws, or allegations of such violations, could result in fines, penalties or prosecution and have a negative impact on our business, results of operations and reputation.

Coverage and Reimbursement

Sales of pharmaceutical products depend significantly on the extent to which coverage and adequate reimbursement are provided by third-party payors. 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 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. In the U.S., no uniform policy of coverage and reimbursement for drugs or biological products exists, and one payor’s determination to provide coverage and adequate reimbursement for a product does not assure that other payors will make a similar determination. In the U.S., the principal decisions about reimbursement for new medicines are typically made by the CMS, an agency within the HHS, as the CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare. Private third-party payors tend to follow Medicare coverage and reimbursement limitations to a substantial degree but also have their own methods and approval processes apart from Medicare determinations. Significant uncertainty exists as to the reimbursement status of newly approved healthcare products.

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The U.S. 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. Adoption of price controls and cost containment measures and adoption of more restrictive policies in jurisdictions with existing controls and measures could further limit our revenues and results. We may need to conduct expensive clinical trials to demonstrate the comparative cost-effectiveness of our product candidates. The product candidates that we develop may not be considered cost-effective and thus may not be covered or sufficiently reimbursed. It is time consuming and expensive for us to seek coverage and reimbursement from third-party payors, as each payor will make its own determination as to whether to cover a product and at what level of reimbursement. Thus, one payor’s decision to provide coverage and adequate reimbursement for a product does not ensure that another payor will provide coverage or that the reimbursement levels will be adequate. Moreover, a payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Reimbursement may not be available or sufficient to allow us to sell our product candidates on a competitive and profitable basis.

Healthcare Reform

The U.S. and some foreign jurisdictions are considering or have enacted a number of legislative and regulatory proposals to change the healthcare system in ways that could affect our ability to sell our product candidates profitably. Among policy makers and payors in the U.S. and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the U.S., the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.

By way of example, in March 2010, the ACA was signed into law, intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms. Among the provisions of the ACA of importance to our potential product candidates are:

•an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents, apportioned among these entities according to their market share in certain government healthcare programs;

•an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13.0% of the average manufacturer price for branded and generic drugs, respectively;

•a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;

•a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70% (increased pursuant to the Bipartisan Budget Act of 2018, effective as of 2019) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for a manufacturer’s outpatient drugs to be covered under Medicare Part D;

•extension of a manufacturer’s Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations;

•expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals and by adding new mandatory eligibility categories for certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability;

•expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program; and

•a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.

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In addition, other legislative changes have been proposed and adopted since the ACA was enacted. These changes include, among others, the Budget Control Act of 2011, which mandates aggregate reductions to Medicare payments to providers of up to 2% per fiscal year effective April 1, 2013, and, due to subsequent legislative amendments, will remain in effect through 2032. In January 2013, President Obama signed into law the ATRA, which, among other things, further reduced Medicare payments to several providers, including hospitals and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. 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.

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 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. 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. Complying with any new legislation and regulatory changes could be time-intensive and expensive, resulting in a material adverse effect on our business.

Since the enactment of the ACA, there have been judicial and Congressional challenges to certain aspects of the ACA. In June 2021, the United States Supreme Court held that Texas and other challengers had no legal standing to challenge the ACA, dismissing the case without specifically ruling on the constitutionality of the ACA. Accordingly, the ACA remains in effect in its current form. It is possible that the ACA will be subject to judicial or Congressional challenges in the future. It is unclear how additional challenges and healthcare reform measures will impact the ACA. Complying with any new legislation or changes in healthcare regulation could be time-intensive and expensive, resulting in material adverse effect on our business.

At the state level, individual states are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including discounts, restrictions on certain product access and marketing cost disclosure and transparency measures. For example, a number of states are considering or have recently enacted state drug price transparency and reporting laws that could substantially increase our compliance burdens and expose us to greater liability under such state laws once we begin commercialization after obtaining regulatory approval for any of our products. For example, the FDA has authorized the state of Florida to develop a program to import certain prescription drugs from Canada for a limited period to help reduce drug costs, provided that Florida’s Agency for Health Care Administration meets the requirements set forth by the FDA. Other states may follow Florida. These measures could reduce the demand for our products, if approved, or impose additional pricing pressures on how much we can charge for our products if approved.

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We expect that the ACA, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and lower reimbursement and additional downward pressure on the price that we receive for any approved product. Any reduction in reimbursement from Medicare or other government-funded programs may result in a similar reduction in payments from private payors. 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. Furthermore, the current presidential administration and Congress may continue to attempt broad sweeping changes to the current health care laws. We face uncertainties that might result from modifications or repeal of any of the provisions of the ACA, including as a result of current and future executive orders and legislative actions. The impact of those changes on us and potential effect on the pharmaceutical and biotechnology industries as a whole is currently unknown. However, any changes to the ACA are likely to have an impact on our results of operations and may have a material adverse effect on our results of operations. We cannot predict what other healthcare programs and regulations will ultimately be implemented at the federal or state level or the effect any future legislation or regulation in the U.S. may have on our business.

Foreign Regulation

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.

HUMAN CAPITAL

Overview

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.

Leadership

Dr. Patrick Soon-Shiong, Executive Chairman and Global Chief Scientific and Medical Officer

Dr. 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. Dr. 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

Mr. 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.

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ImmunityBio is committed to building a workplace that values diversity in thought and perspective and that reflects the patient populations we serve.

•Gender: approximately 50%/50% male/female

•Race: approximately 41% white; 56% other; and the remainder declined to report

Talent Development, Attraction, and Retention

Our ability to attract and retain top talent is essential to our strategy. 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 talent. 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.

•Benefits: 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.

ImmunityBio, Inc. is incorporated in Delaware and its principal executive offices are located in San Diego, California. The company operates in one operating and one reportable segment. ImmunityBio, Inc. was established following a series of mergers and name changes. For more information regarding ImmunityBio’s development, see Part I, Item 1. “Business—Organization and Development of ImmunityBio, Inc.” of our Annual Report filed with the SEC on March 19, 2024.

AVAILABLE INFORMATION

Financial and other information about our company is available on our website at https://www.immunitybio.com. We make available on our website, free of charge, copies of our Annual Report, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and all amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act as soon as reasonably practicable after such reports are electronically filed with, or furnished to, the SEC. All reports we file with the SEC are available free of charge via EDGAR through the SEC website at https://www.sec.gov. 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 is not part of this filing.