Artiva Biotherapeutics, Inc.

Overview

We are a clinical-stage biotechnology company focused on developing natural killer (NK) cell-based therapies for patients suffering from devastating autoimmune diseases and cancers. Our product candidates are derived from donor cells (allogeneic) rather than a patient’s own cells (autologous) and are pre-manufactured and stored frozen and ready to ship to a patient’s treatment location, making them what we believe to be “off-the-shelf.” Our lead product candidate, AlloNK (also known as AB-101), is an allogeneic, non-genetically modified, cryopreserved NK cell therapy designed to enhance the antibody-dependent cellular cytotoxicity (ADCC) effect of monoclonal antibodies (mAbs) to drive B-cell depletion. We are currently evaluating AlloNK in three ongoing clinical trials for the treatment of B-cell driven autoimmune diseases, including a company-sponsored basket trial across autoimmune diseases that includes rheumatoid arthritis (RA) and Sjögren’s disease (SjD). We are prioritizing refractory RA as our lead indication for AlloNK development. We expect to share initial clinical response data across dose levels from more than 15 refractory RA patients, several of whom will have 6 months or more follow up, in the first half of 2026. In addition, we plan to conduct FDA regulatory interactions in the first half of 2026 to align on the pivotal trial design for AlloNK in refractory RA.

Seminal peer-reviewed clinical studies using autologous CD19 chimeric antigen receptor (CAR) T-cell therapy (auto-CAR-T) for the treatment of autoimmune diseases have demonstrated that deep B-cell depletion in the periphery and in the lymphoid tissue can lead to high rates of clinical response and durability after a single cycle of treatment. We have demonstrated deep depletion of peripheral B cells in patients with autoimmune disease. In November 2025, we reported data from 32 patients with autoimmune disease treated with AlloNK plus anti-CD20 monoclonal antibody (mAb) as of October 1, 2025, data cutoff, showing consistent and complete B-cell depletion by Day 13 of treatment in all patients treated with AlloNK + mAb with samples analyzed. We believe this demonstration of complete peripheral B-cell depletion suggests that the regimen may achieve robust and durable clinical responses. Further, we observed complete responses (CRs) in heavily pre-treated patients naïve to auto-CAR-T in a Phase 1/2 clinical trial in patients with relapsed or refractory B-cell-non-Hodgkin lymphoma (B-NHL) treated with AlloNK in combination with the CD20-targeted mAb rituximab. We believe the preliminary results from B-NHL provide a readthrough to autoimmune disease because efficacy in both diseases appears to be accomplished with a shared mechanism of action involving B-cell depletion in the periphery and in the lymphoid tissues, followed by an immunological reset and B-cell reconstitution.

To our knowledge, AlloNK was the first allogeneic, off-the-shelf NK cell therapy candidate to receive Investigational New Drug application (IND) clearance to be administered to a patient with an autoimmune disease in a U.S. clinical trial, and to receive United States Food and Drug Administration (FDA) Fast Track designation in an autoimmune disease. Artiva has received Fast-Track Designation in RA and lupus nephritis (LN). Additionally, to our knowledge, AlloNK is the first allogeneic NK cell therapy candidate in the United States to receive IND clearance for a basket trial in autoimmune diseases, and specifically the first to be evaluated in RA and SjD. We believe as we continue to execute on our strategic plan that these critical first mover advantages will solidify our leadership in multiple autoimmune diseases with high unmet need. Receiving IND clearance and any special designations, such as Fast Track designation, does not guarantee clinical success, an accelerated review of AlloNK or increase the likelihood of approval of AlloNK by the FDA. Given our stage of development, it will take several years before we complete clinical development and receive regulatory approval of AlloNK or any of our product candidates, if at all.

B-Cell Driven Autoimmune Disease Background, Prevalence and Unmet Need

Many autoimmune diseases occur when autoreactive B-cells produce autoantibodies that target the body’s own healthy cells and tissues, which can lead to significant morbidity and use of chronic immunosuppressants including glucocorticosteroids. This presents an opportunity to develop treatments that deplete B-cells in a variety of autoimmune diseases such as RA, SjD, systemic sclerosis (SSc), myositis / idiopathic inflammatory myopathies (IIMs), systemic lupus erythematosus (SLE), LN, ANCA vasculitis, multiple sclerosis (MS) and myasthenia gravis (MG), which together account for approximately 7.9 million patients in the United States and Europe alone. Global sales for autoimmune disease, treatments for which in 2023 reached approximately $160 billion (including $65 billion for the top ten immunology and inflammation drugs focused on rheumatology) and represent the second-largest class of spending behind oncology, are expected to continue to grow.

In RA in particular, conventional synthetic disease-modifying drugs (csDMARDs) such as methotrexate (MTX) are typically used as first line therapy, followed by biological or targeted synthetic DMARDs (b/tsDMARDs). In the US, 6 classes of b/tsDMARDs are approved for the treatment of RA including anti-TNF, anti–IL-6R, IL-1 receptor antagonist, CTLA-4–Ig, anti-CD20, and JAK inhibitors. Responses have been shown to progressively and significantly decrease following inadequate responses to 2 or more distinct classes of b/tsDMARDs, leading to disease progression and long-term joint damage may continue. There are approximately 150,000-200,000 RA patients in the US alone who have failed 2 or more b/tsDMARDs.

While auto-CAR-T cell therapies have demonstrated the transformative potential of cell therapy, adoption has been limited since their initial approvals due to several factors, including but not limited, to safety, patient access, and scalability. Further, T-cell engager (TCE) approaches may address some of these challenges, such as patient access and scalability, but still have safety liabilities. We believe AlloNK in combination with B-cell targeted mAbs represents the next-generation of B-cell depleting therapies because it aims to address important limitations of T-cell-based approaches, including:

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Scalability: AlloNK can be manufactured at scale, cryopreserved, easily transported through cold-chain logistics, and we believe be made readily available for patients. In contrast, auto-CAR-T requires a complex, costly, and lengthy manufacturing process that is individualized for each patient. The need for hospitalization further compounds the challenges of scalability and access, adding financial burden to the healthcare system. For example, toxicity and extended hospitalization from treatment with auto-CAR-T could add an incremental financial burden of over $1 million per patient. The scalability of our process creates the potential to expand treatment access to the many autoimmune patients annually who currently live with the consequences of long-term steroid use.

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Safety: Therapies utilizing a T-cell-based mechanism, including autologous and allogeneic CAR-T cell as well as TCEs, are associated with immune effector cell-associated neurotoxicity syndrome (ICANS), cytokine release syndrome (CRS) and other severe adverse events, and treatment is generally only available at advanced clinical centers capable of supporting these patients. Conversely, in our clinical trials of AlloNK in combination with anti-CD20 mAbs in autoimmune disease, all patients were treated as outpatients, and the majority were treated at community rheumatology trial sites with no specialized oncology oversight, demonstrating feasibility of AlloNK administration and patient management in the community setting. In the first 32 patients treated, as of an October 1, 2025 data cutoff, no CRS or ICANS was reported. Only one patient was hospitalized for an adverse event (a skin infection unrelated to AlloNK) in the 28-day window post treatment. We believe this demonstrates the ability of AlloNK to be administered and managed in an outpatient setting, with limited risk of required hospitalization.

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Cost: Cost of goods sold (COGS) to manufacture auto-CAR-Ts is estimated at over $100,000 per treatment course, limiting flexibility in therapy pricing. Conversely, commercial COGS for AlloNK per patient would be below a range of $3,000 to $12,000, approximately an order of magnitude below the current COGS of auto-CAR-T. We have the potential to treat 1,000 autoimmune patients per year just from our current manufacturing facility, with the ability to scale out to support commercialization. As auto-CAR-Ts move from their currently marketed indication of hematological malignancies towards chronic and more prevalent autoimmune diseases, AlloNK’s extremely competitive commercial COGS could allow for advantageous pricing flexibility and payor coverage, if approved.

Our Pipeline

Our lead product candidate, AlloNK, is currently being evaluated in combination with B-cell targeted mAbs in patients with autoimmune diseases including RA, SjD, SSc, and IIMs. We are prioritizing refractory RA as our lead indication for AlloNK development. In addition, we are also pursuing our CAR-NK product candidates in multiple indications through collaborator-funded trials. Our current pipeline is depicted below.

Note: Artiva holds ex-APAC rights to all programs.

Note: RA: Rheumatoid Arthritis; SjD: Sjögren’s Disease; SLE: Systemic Lupus Erythematosus; SScl Systemic Sclerosis; LN: Lupus Nephritis; IIMs: Idiopathic Inflammatory Myopathies; AAV: Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV); PV: Pemphigus Vulgaris; NHL: Non-Hodgkin lymphoma

(1) Investigator-Initiated Basket Trial

(2) Trial completed; Trial in close-out after decision to discontinue the remaining long-term follow-up period

AlloNK Overview

Our lead product candidate, AlloNK, is a non-genetically modified, cryopreserved NK cell therapy being evaluated in combination with B-cell targeted mAbs in three ongoing clinical trials for the treatment of B-cell driven autoimmune diseases, including a company sponsored Phase 2a basket trial in multiple autoimmune indications including RA and SjD and a basket investigator-initiated trial (IIT) in B-cell driven autoimmune indications. The sites within the trials are community rheumatology trial sites with no specialized oncology oversight, demonstrating feasibility of AlloNK administration and patient management in the community setting. AlloNK is also being investigated a company-sponsored Phase 1 study testing AlloNK in combination with rituximab or obinutuzumab in patients with SLE or LN.

AlloNK in combination with rituximab has been granted Fast Track designation by the FDA in October 2025 in patients with refractory RA. We have completed enrollment in our Phase 1/1b clinical trial in combination with rituximab or obinutuzumab in patients with SLE or LN, and are actively enrolling our company-sponsored Phase 2a basket trial in multiple autoimmune indications including RA and SjD. As of the data cutoff date on October 1, 2025, 32 patients have been treated with AlloNK plus anti-CD20 monoclonal antibody therapy across refractory RA, SjD, SLE, LN and SSc in the two company-sponsored trials and the IIT. In addition, AlloNK in combination with rituximab or obinutuzumab has been granted Fast Track designation by the FDA to improve disease activity in patients with class III or class IV LN. Fast Track designation does not guarantee clinical success, an accelerated review of AlloNK or increase the likelihood that AlloNK will receive regulatory approval by the FDA.

In April 2024, the FDA cleared an IND submitted by Integral Rheumatology & Immunology Specialists (IRIS), a large community practice rheumatology clinic in Florida, to conduct a basket IIT to assess the safety, tolerability and clinical activity of AlloNK in combination with rituximab in patients with RA, PV, the ANCA-associated vasculitis subtypes GPA / MPA and SLE. We supply AlloNK and funding for the IIT, but unlike our sponsored clinical trials, IRIS is the regulatory sponsor of, and responsible for, the conduct of the IIT. Treatment of the first patient in the basket IIT was initiated in August 2024.

We intend to pursue additional autoimmune diseases with AlloNK in combination with B-cell targeted mAbs.

Because AlloNK can be used with mAbs that target different antigens based on the target cell’s antigen expression, we believe we have the versatility to use AlloNK in combination with different mAbs to deplete distinct B-cell subpopulations. AlloNK has the potential to be used with a CD19 or CD20 targeting mAb to determine which drives a more robust response. Furthermore, emerging evidence with auto-CAR-T targeting B-cell maturation antigen (BCMA), a plasma cell antigen, either alone or dual-targeted with CD19, has shown distinct therapeutic activity in several indications when compared with CD19-only auto-CAR-T. We believe AlloNK in combination with approved anti-CD38 mAbs could target a similar plasma cell population. We believe this versatility will enable us to pursue a wider range of indications than cell therapies engineered against specific targets.

Our Collaborator-Funded Trials

We previously entered into a strategic collaboration agreement with Affimed GmbH, a subsidiary of Affimed N.V. (Affimed), whereby we investigated AlloNK in a Phase 2 trial in combination with acimtamig, a CD30-targeted NK cell engager, in CD30+ Hodgkin lymphoma (HL). In May 2025, Affimed filed for insolvency and in July 2025, we terminated our collaboration agreement with Affimed.

In addition, we own exclusive worldwide rights (excluding Asia, Australia and New Zealand (ex-APAC)) for AB-201, a human epidermal growth factor receptor 2 (HER2) targeting CAR-NK cell product candidate, and for AB-205, a CD5 directed CAR-NK cell product candidate.

Manufacturing Capabilities

We have a manufacturing-first approach, referencing the fact that even before we were founded, our strategic partner, GC Cell, had already invested years pioneering the manufacturing process that we use today. Unlike most other companies in the NK field who started clinical development before establishing a scalable manufacturing process, we started clinical development with a mature and robust process in place. Our process is designed to allow us to produce off-the-shelf, allogeneic NK cell therapy candidates and to potentially meet the scale of commercial demand, with the mission to make these therapies broadly accessible for patients with devastating autoimmune diseases and cancers. We leveraged our deep expertise in NK cell biology to establish an end-to-end proprietary process in collaboration with GC Cell. In our San Diego headquarters, we have established a 9,000 square foot, purpose-built cell production center that is compliant with current Good Manufacturing Practices (cGMP). At the dose levels currently being tested, with an aggregate of three billion to twelve billion AlloNK cells total per patient, AlloNK COGS per patient in the commercial setting would be below a range of $3,000 to $12,000, approximately an order of magnitude below the current COGS of auto-CAR-T.

Our Management Team, History and Investors

We were founded in 2019 as a spin out of GC Cell, formerly GC Lab Cell Corporation, a leading healthcare company in the Republic of Korea (Korea), pursuant to a strategic partnership granting us exclusive, worldwide, ex-APAC, rights to GC Cell’s NK cell manufacturing technology and programs. GC Cell has an established track record in cell therapy, with over two decades of cell therapy research, process development and manufacturing experience, as well as a clinical and commercial track-record outside the United States with the first ever marketed T-cell product, Immuncell-LC, which received South Korean Ministry of Food and Drug Safety (MFDS) approval for hepatocellular carcinoma in 2017. An investigational version of the product candidate also received FDA Orphan Drug Designation for pancreatic cancer, liver cancer and glioblastoma in 2018. In addition, GC Cell spent over a decade optimizing the manufacturing process for NK cell therapeutics, including selection of cord blood as a starting material, expanding process scale and enabling cryopreservation. GC Cell utilizes a custom-built 300,000 square foot cell therapy research, process development and cGMP manufacturing facility from which we were able to produce drug product for our first clinical trials in the United States.

Our team is led by executives who have deep experience in their respective functions in cell therapy with multi-faceted experience across a company’s life cycle. Our leadership team has extensive combined experience in therapeutics, medical devices and diagnostics companies. We have also assembled scientific advisors with deep experience in both cell therapy and autoimmune disease who are actively involved in our drug development process and programs.

Our Mission

Our mission is to develop effective, safe and accessible cell therapies for patients with devastating autoimmune diseases and cancers.

Our Strengths

We believe that our company and therapeutic candidates possess the following competitive strengths.

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Autoimmune disease treatment approach supported through complete peripheral B-cell depletion patients with autoimmune disease and complete responses observed in lymphoid tissues of patients with B-cell NHL. Our conviction in the clinical translation of our proposed mechanism of action is driven by preliminary data observed from our three ongoing clinical trials in autoimmune disease, as well as from our completed Phase 1/2 clinical trial of AlloNK in combination with rituximab in patients with relapsed or refractory B-NHL. In November 2025, we reported data from 32 patients with autoimmune disease treated with AlloNK plus anti-CD20 mAb as of October 1, 2025, data cutoff, showing consistent and complete B-cell depletion. Specifically, all 23 patients with samples analyzed demonstrated non-quantifiable peripheral CD19+ B-cell levels by Day 13 of treatment, irrespective of baseline B-cell counts. Similarly, results from a high-sensitivity B-cell depletion assay with 10- to 50-fold higher sensitivity than typical assays demonstrated non-quantifiable peripheral CD19+ B-cell levels, further supporting the intended mechanism of action for AlloNK. B-cell reconstitutions in the four patients treated with AlloNK + rituximab who had achieved B-cell reconstitution as of the data cutoff demonstrated predominantly naïve and transitional cells at the time of reconstitution, in line with what has been observed with CD19-auto-CAR-T treatment. The depth and consistency of B-cell depletion are comparable to those achieved with CD19-auto-CAR-T cell therapies and meaningfully greater than rituximab alone as reported in published studies. We believe this data provides support for a B-cell depleting mechanism of action of AlloNK in combination with B-cell targeted mAbs. AlloNK in combination with rituximab has also demonstrated CRs in B-NHL patients as measured by imaging of tumor lesions. Because of the common tissues of interest, principally the lymphoid tissues, in B-NHL and autoimmune diseases, we believe data in these B-NHL patients provides supporting evidence for our proposed mechanism of action in autoimmune disease. In the Phase 1 portion of this trial, as of October 22, 2025, in the fourteen patients who were naïve to CAR-T, the complete response rate (CRR) was 64%, as determined by the Lugano 2014 criteria. The Lugano 2014 criteria is a widely accepted and published methodology used in clinical trials as well as in clinical practice for response assessment in lymphoma. The criteria recommend a combination of disease morphology assessment using computed tomography (CT) and lesion metabolic activity assessment on positron emission tomography (PET), with PET metabolic assessments being the driver for overall response assessment. As of the October 22, 2025 data cutoff date, five of the nine patients with a CR had an ongoing response (meaning continuation of the CR at all follow-up points), with median duration of response (DOR) not reached, but at least 19.4 months. The longest responder remained progression free for at least 24 months after the start of treatment. We believe these data support that AlloNK in combination with B-cell targeted mAbs has the potential to provide deep B-cell depletion in common target tissues between B-NHL and autoimmune diseases and offer therapeutic potential, a differentiated safety profile and patient accessibility in numerous autoimmune diseases.

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Versatile mAb combination approach allows flexibility to tailor targeting approach to specific B-cell subpopulations. Because AlloNK can be used with mAbs that target different antigens based on the target cell’s antigen expression, we believe we have the versatility to use AlloNK in combination with different mAbs to deplete distinct B-cell subpopulations. AlloNK has the potential to be used with a CD19 or CD20 targeting mAb to determine which drives a more robust response. Furthermore, emerging evidence with auto-CAR-T targeting B-cell maturation antigen (BCMA), a plasma cell antigen, either alone or dual-targeted with CD19, has shown distinct therapeutic activity in several indications when compared with CD19-only auto-CAR-T. We believe AlloNK in combination with approved anti-CD38 mAbs could target a similar plasma cell population. We believe this versatility will enable us to pursue a wider range of indications than cell therapies engineered against specific targets.

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Proprietary manufacturing process allows for scalable and potentially cost effective AlloNK production. Our robust chemistry, manufacturing and controls (CMC) experience, ample capacity and limited overhead enable us to produce allogeneic, off-the-shelf, NK cell therapy candidates at scale. Utilizing our proprietary process we and GC Cell have manufactured over 50 clinical batches of AlloNK, producing thousands of AlloNK vials at one billion cells per vial, and have demonstrated both batch-to-batch and donor-to-donor consistency. Our manufacturing platform and scale-up process is rooted in over a decade of NK cell expansion experience by our strategic partner, GC Cell, and has been further improved upon by our team. In our San Diego headquarters, we have established a 9,000 square foot, purpose-built cell production center that is cGMP-compliant. At the dose levels currently being tested, with an aggregate of three billion to twelve billion AlloNK cells total per patient, AlloNK COGS per patient in the commercial setting would be below a range of $3,000 to $12,000, approximately an order of magnitude below the current COGS of auto-CAR-T. With this COGS, we could have the flexibility to reduce the price relative to auto-CAR-T while still maintaining a high margin.

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Non-genetically modified cell therapy has not shown integrating vector-induced secondary malignancies, which is a benefit in an autoimmunity setting. As of December 31, 2023, the FDA had received reports of 22 cases of secondary T-cell malignancies (including CAR+ lymphoma) in patients who received treatment with BCMA- or CD19-directed genetically modified auto-CAR-T therapy. Transgene insertion of CAR was detected in the malignant clone in each of the three cases for which genetic sequencing was performed. As a result, in January 2024, the FDA determined that boxed warning language addressing these malignancies should be included on the label for all BCMA- and CD19-directed genetically modified auto-CAR-Ts to alert patients and clinicians of the potential risk of developing secondary T-cell malignancies following treatment. Unlike CAR-T and any genetically modified cell therapy, AlloNK is a non-genetically modified NK cell therapy candidate and has not shown any secondary malignancies either in our NHL clinical trial, as of an October 22, 2025 database lock, or in our autoimmune clinical trials, as of February 12, 2026. We believe this will make our therapeutic candidate a preferable and differentiated treatment option for physicians and patients.

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AlloNK cell approach aims to broaden community access, drive improved patient experience, improve clinical recruitment timelines and expand commercial opportunity. In our clinical trials to date, AlloNK in combination with a B-cell targeted mAb was mostly administered and managed outside of a hospital setting. This is in contrast to auto-CAR-T cell therapies, which have been limited by the need for hospitalization due to the risks of ICANS and CRS, among other severe adverse events. Our product candidate is designed to enable rheumatologists to administer AlloNK in combination with a B-cell targeted mAb within their own outpatient infusion centers, potentially allowing patients to avoid the typically required hospitalization associated with CAR-T cell therapies. These limitations are also present for T-cell engaging bispecific antibodies. Approved T-cell engaging bispecific antibodies such as glofitamab, epcoritamab, and mosunetuzumab require hospitalization upon dosing due to the risk of CRS. We believe the potential to administer an off-the-shelf therapy in an outpatient setting could meaningfully reduce the patient’s treatment burden, translating to a potential competitive advantage in enrolling patients in our clinical trials and capturing market share, if approved.

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Strategic execution led to first-mover advantage in autoimmune disease. We have advanced AlloNK into clinical trials for autoimmune diseases, and we believe we have achieved multiple critical clinical and regulatory milestones ahead of other allogeneic, off-the-shelf NK cell therapy companies. Specifically, the FDA cleared our IND for AlloNK in combination with rituximab for our Phase 1/1b clinical trial in patients with class III or IV LN in August 2023, and we dosed the first patient in this trial in April 2024. To our knowledge, this made AlloNK the first allogeneic, off-the-shelf NK cell therapy candidate to be administered to a patient with an autoimmune disease in a U.S. clinical trial and the first allogeneic, off-the-shelf NK cell therapy to receive Fast Track designation in an autoimmune indication. Further, in April 2024, the FDA cleared an IND submitted by IRIS, a large community practice rheumatology clinic in Florida, to conduct a basket IIT in multiple autoimmune indications. Treatment of the first patient in this basket IIT was initiated in August 2024. Through this IIT, to our knowledge, AlloNK is the first allogeneic NK cell therapy candidate in the United States to receive allowance to proceed with a basket study under an IND, and specifically the first to be evaluated in RA, PV and AAV, which we believe solidifies our potential leadership in multiple large-market diseases. Further, the FDA cleared our IND for AlloNK in combination with rituximab for our Phase 2 basket study in May 2025, which, to our knowledge, made AlloNK the first allogeneic NK cell therapy candidate in the United States to be evaluated in SjD. AlloNK in combination with rituximab has been granted Fast Track designation by the FDA in October 2025 in patients with refractory RA.

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We believe our established manufacturing capabilities empower us to capitalize on our first-mover advantage to efficiently develop and, if approved, potentially commercialize a wide range of indications relative to auto-CAR-Ts, which we believe are constrained due to the limitations associated with manufacturing autologous cell therapies. We believe all of these potential advantages, along with our expected competitive advantage in enrollment timing, will allow us to efficiently progress AlloNK through the clinic and position us to capitalize on the broad market opportunity of B-cell driven autoimmune diseases. Receiving IND clearance and any special designations, such as Fast Track designation, does not guarantee an accelerated review of AlloNK or increase the likelihood of approval of AlloNK by the FDA. Given our stage of development, it will take several years before we complete clinical development and receive regulatory approval of AlloNK or any of our product candidates, if at all.

Our Strategy

Our strategy is to develop safe and effective NK cell-based therapies that patients and physicians can utilize in a community setting. We believe the compelling cell killing properties of NK cells, when combined with mAbs for targeting specific antigens, creates an opportunity to generate potentially transformative therapies. Key elements of our strategy include:

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Advance our lead product candidate, AlloNK, through clinical development in RA and demonstrate the broad clinical potential of NK cell therapies in autoimmune diseases. We are advancing AlloNK through clinical development to address the significant unmet need in autoimmunity as well as patient and physician desire for a safe, accessible therapy. The FDA cleared our IND for AlloNK in combination with rituximab for our Phase 2 basket study in May 2025. We have subsequently reported safety and translational data from 32 patients dosed across this study and our other two ongoing studies in autoimmune disease, as of an October 1, 2025 data cutoff date. We are prioritizing refractory RA as our lead indication for AlloNK development and expect to share initial clinical response data across dose levels from more than 15 refractory RA patients, several of whom will have 6 months or more follow up, in the first half of 2026. In addition, we plan to conduct FDA regulatory interactions in the first half of 2026 to align on the pivotal trial design for AlloNK in refractory RA. We plan to develop AlloNK in additional autoimmune indications as response data from our ongoing Phase 1 and Phase 2 studies matures.

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Demonstrate the clinical potential of NK cell therapies to address limitations of auto-CAR-Ts. Auto-CAR-Ts have proven to be an effective therapeutic modality in cancer and have shown therapeutic clinical benefit in autoimmune disease. We believe this is the first step in an evolution where next generations of the technology will improve safety and expand access to the point where cell therapies truly are available to any patient in need. We have optimized an end-to-end NK cell manufacturing process to potentially deliver AlloNK on a large scale and at low cost, having leveraged more than a decade of NK cell manufacturing expertise and know-how. We believe AlloNK in combination with B-cell targeted mAbs represents the next-generation of B-cell depleting therapies because it aims to address important limitations of auto-CAR-T, including:

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Scalability: AlloNK is an allogeneic, off-the-shelf product candidate that can be manufactured at scale, cryopreserved, easily transported through cold-chain logistics and we believe can be made readily available for patients. In contrast, auto-CAR-T therapy requires a complex, costly, and lengthy manufacturing process that is individualized for each patient. The need for hospitalization further compounds the challenges of scalability and access, adding financial burden to the healthcare system. For example, toxicity and extended hospitalization from treatment with auto-CAR-T could add an incremental financial burden. According to a real-world study conducted in 2021 by Oregon Health & Science University and presented by Maziarzet al. the average cost of treatment, excluding the cost of auto-CAR-T itself, was $383,000 and could reach over $1 million per patient. In contrast, we reported that in the first 9 RA and SLE patients treated in our IIT at a single community rheumatology site, the mean non-AlloNK cost per patient, inclusive of all other study drugs, procedures, and AE management, was $18,301 per patient. The scalability of our process creates the potential to expand treatment access to the many autoimmune patients annually who currently live with the consequences of long-term steroid use.

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Safety: As a result of autologous and allogeneic CAR-Ts’ association with CRS, ICANS, and other severe adverse events, treatment is generally only available at advanced clinical centers capable of supporting these patients. Conversely, in the first 32 autoimmune patients treated, as of an October 1, 2025 data cutoff, no CRS or ICANS was reported, and most treatment-emergent adverse events (TEAEs) were Grade 1 or 2, transient, and consistent with expected effects of Cy and Flu conditioning. Infection rates were similar to those observed with approved biologics for RA, and only one patient of the first 32 was hospitalized for an adverse event (a skin infection unrelated to AlloNK) in the 28-day window post treatment. Data as of the cutoff date suggest that overall patient and physician experience and the emerging tolerability profile are consistent with the treatment journey typically observed with intravenous mAb therapies.

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Cost: Cost of goods to manufacture auto-CAR-Ts is estimated at over $100,000 per treatment course, limiting flexibility in therapy pricing. Assuming a range of one billion to four billion AlloNK cells per dose and three doses for a treatment regimen of an aggregate of three billion to twelve billion AlloNK cells total per patient with autoimmune disease, AlloNK COGS per patient would be below a range of $3,000 to $12,000, approximately an order of magnitude below the current COGS of auto-CAR-T. As auto-CAR-Ts move from their currently marketed indication of hematological malignancies towards chronic and more prevalent autoimmune diseases, AlloNK’s extremely competitive commercial COGS could allow for advantageous pricing flexibility and payor coverage, if approved.

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Continue to evaluate and pursue tailored strategies to advance our platform capabilities and maximize patient access to AlloNK. We have a disciplined strategy to evaluate partnerships that are designed to further our NK cell development and manufacturing efforts with the goal of delivering our product candidates to as many patients as stand to benefit. We also plan to commercialize our product candidates and will look to make further investments at the appropriate time to maximize access and the commercial potential of our product candidates.

Introduction to Autoimmune Disease

Background

Many autoimmune diseases occur when autoreactive B-cells produce autoantibodies that target the body’s own healthy cells and tissues instead of foreign pathogens. In a healthy individual, these malfunctioning immune cells, such as B-cells and T-cells, are either eliminated before they fully develop or are kept in check by various regulatory mechanisms. However, in individuals with autoimmune diseases, these safety measures are compromised due to a mix of genetic factors and exposure to certain antigens from infections or environmental sources.

The prevalence of autoimmune diseases is both widespread and growing, with over 80 known autoimmune diseases. The persistent and severe nature of these diseases results in substantial medical expenses and a decline in quality of life, posing significant challenge for patients, their families and the healthcare system. Global sales for autoimmune disease, treatments for which in 2023 reached approximately $160.0 billion (including $65 billion for the top ten immunology and inflammation drugs focused on rheumatology) and represent the second-largest class of spending behind oncology, are expected to continue to grow. There is a significant unmet medical need in autoimmune diseases despite the number of approved therapies, given these treatments are often not curative and many patients do not achieve optimal outcomes.

B-Cell Driven Autoimmune Diseases

Autoimmune diseases encompass a broad range of diseases and symptoms, with the presence of autoantibodies—produced by autoreactive B-cells that mistakenly target the body’s healthy cells and tissues—being a common characteristic of many autoimmune diseases. While the specific autoantigen targeted and the primary affected tissue or organ may vary, the role of B-cells in producing these autoantibodies is generally consistent. Increasing evidence suggests that autoreactive B-cells also contribute to the pathology of many autoimmune diseases through their interaction with T-cells and cytokine production. This shared biological mechanism presents an opportunity to develop treatments targeting the production of autoantibodies by B-cells for a variety of autoimmune diseases.

The following table sets forth the estimated prevalence for select B-cell-driven autoimmune diseases in the United States and in Europe.

All figures for Europe are for geographic Europe, except δ: which is for the European Union.

Unmet Need in RA

In RA, csDMARDs such as MTX are typically used as first line therapy, followed by b/tsDMARDs. In the US, 6 classes of b/tsDMARDs are approved for the treatment of RA including anti-TNF, anti–IL-6R, IL-1 receptor antagonist, CTLA-4–Ig, anti-CD20, and JAK inhibitors. Responses have been shown to progressively and significantly decrease following inadequate responses to 2 or more distinct classes of b/tsDMARDs, leading to disease progression and long-term joint damage may continue. There are approximately 150,000-200,000 RA patients in the US alone who have failed 2 or more b/tsDMARDs.

Our Solution – AlloNK

Our lead product candidate, AlloNK is an allogeneic, non-genetically modified, cryopreserved NK cell therapy candidate designed to enhance the ADCC effect of mAbs to drive B-cell depletion. Using our proprietary cell therapy manufacturing platform, we can generate thousands of doses of cryopreserved, infusion-ready AlloNK from a single cord blood unit.

AlloNK is being studied in combination with rituximab in a company-sponsored Phase 2 basket trial, currently enrolling patients with 4 autoimmune diseases (RA, SjD, SSc and IIMs) at sites across the United States and Europe. In this study, all patients are treated as outpatients, and the majority of sties are community rheumatology trial sites with no specialized oncology oversight, demonstrating feasibility of AlloNK administration and patient management in the community setting. AlloNK is also being investigated in two additional clinical trials in patients with autoimmune disease: a company-sponsored Phase 1 study testing AlloNK in combination with rituximab or obinutuzumab in patients with SLE or LN; and a Phase 1 IIT testing AlloNK in combination with rituximab in patients with RA, PV, AAV, and SLE.

NK Cell Background

NK cells are part of the innate immune system, which is the body’s first line of immune surveillance and defense. NK cells modulate their activity through a balance of activating and inhibiting receptors on their surface that engage with their environment including with target cells. This balance enables NK cells to recognize and kill abnormal cells while suppressing cytotoxic responses to normal tissue, thereby providing a population of immune effector cells that defend against cancer and virus-infected cells. NK cells naturally work in concert with antibodies. The antibody first binds to a target on a diseased cell, then to the NK cell via the cell-surface receptor CD16, also known as FcγRIII, which engages the antibody to mount an ADCC response. NK cells may have an advantage over other immune cells, such as the T-cells used in CAR-T cell therapy and other cell therapies, because they can be used as allogeneic therapies, meaning that NK cells from one donor can be administered to one or many patients without the requirement for gene editing or other genetic manipulations.

Schematic of NK Cell Receptor Interaction with

Target Cells. NK Cell Activation via ADCC Leads

to NK-mediated Cytotoxic Activity

To produce AlloNK, we select cord blood units that have a variant of CD16 known as 158 V/V, which has been shown in preclinical studies to lead to increased ADCC activity. The CD16 158V/V point mutation variant encodes for a Fcg RIII receptor that has been shown in preclinical studies to have higher affinity for immunoglobulin G mAbs. In a third-party clinical trial of rituximab, a significantly higher response rate was seen in follicular lymphoma patients with the CD16 genotype encoding the 158 V/V compared to those with other CD16 genotypes. As such, we believe NK cells sourced from donors with the CD16 158 V/V allele will have naturally higher affinity for therapeutic mAbs without the need for genetic engineering of the cell therapy product candidate.

AlloNK, as a non-genetically modified, non-targeted NK cell, is designed to utilize a mAb for targeting. Therefore, we believe different mAbs could be used to target distinct B-cell populations based on the target cell’s antigen expression. For instance, CD19 and CD20 are expressed on memory B-cells, whereas CD38 and BCMA are expressed on plasma cells. Therefore, we believe AlloNK could be combined with different mAbs to kill distinct B-cell populations.

Early Evidence of Mechanism of Action and Activity in Autoimmune Disease

Translational Data from Ongoing Autoimmune Studies

Translational analyses from ongoing clinical studies in autoimmune disease demonstrate that treatment with AlloNK in combination with a CD20 monoclonal antibody results in rapid and consistent peripheral B-cell depletion. As of the October 1, 2025 data cut-off, all 23 evaluable patients with sufficient follow-up achieved B-cell levels below the limit of quantitation, regardless of baseline B-cell counts, with depletion observed by Day 13. Peripheral B-cell reconstitution was observed beginning at approximately six months following treatment, which is generally consistent with the time to reconstitution reported in autoimmune patients treated with rituximab monotherapy.

Importantly, although a CD20-directed antibody was used, B-cell levels were assessed using CD19+ peripheral blood measurements, enabling direct comparison to published datasets across therapeutic modalities. Total immunoglobulin levels largely remained within the normal range, and no cases of hypogammaglobulinemia were reported as of the data cut-off, supporting the potential for deep depletion without overt compromise of humoral immunity.

Note: Preliminary data as of October 1, 2025 data cutoff; Preliminary data from ongoing autoimmune clinical trials: Phase 2a basket trial, Phase 1/1b trial in SLE/LN, investigator-initiated basket trial; Data not cleaned and subject to change

Note: Cy: cyclophosphamide; Flu: fludarabine; mAbs: monoclonal antibodies; RTX: rituximab; OBI: obinutuzumab

Uniform and consistent B-cell depletion observed by Day 13 in all 23 patients with autoimmune diseases treated with Cy / Flu + AlloNK + anti-CD20 mAb (RTX or OBI) with samples analyzed as of data cutoff

To further characterize the depth of B-cell depletion, a high-sensitivity B-cell assay was utilized and contextualized against published literature. Historically, most clinical studies evaluating B-cell depletion, including studies of rituximab and other deep B-cell–depleting therapies, have relied on standard TBNK assays with limits of detection of approximately 5–10 cells per microliter. At this sensitivity, rituximab frequently appears to induce complete depletion. However, published studies using higher-sensitivity assays (with detection limits approximately 10–50 times lower) demonstrate that residual B cells, typically at levels of 1–2 cells per microliter, remain detectable in a substantial proportion of patients treated with rituximab alone. In comparative analyses, approximately 40% of patients in a published cohort of 99 autoimmune patients treated with rituximab had quantifiable B cells when assessed using high-sensitivity assays. In contrast, all autoimmune patients treated to date with the AlloNK regimen have demonstrated non-quantifiable B-cell levels by high-sensitivity assessment.

Note: No head-to-head trial has been conducted evaluating AlloNK against other data included herein. Differences exist between clinical trial design, patient populations and the product candidates/products themselves, and caution should be exercised when comparing data across trials

Preliminary data as of October 1, 2025 data cutoff; Reflects patients with respective follow up as noted on chart for whom samples were analyzed as of the data cutoff.

Preliminary AlloNK data from ongoing autoimmune clinical trials: Phase 2a basket trial, investigator-initiated basket trial Reported numbers subject to change; Lower limit of quantitation (LLOQ)= 0.22 cells /µl.

Note: Cy: cyclophosphamide; Flu: fludarabine; RTX: Rituximab, RA: Rheumatoid Arthritis; SLE: Systemic Lupus Erythematosus

(1) Adapted from Dass et al., Arthritis & Rheumatology (2008) 58(10):2993–99, DOI:10.1002/art.23902, Fig. 3A; and Vital et al., Arthritis & Rheumatology (2011) 63(10):3038–47, DOI:10.1002/art.30466. Data represent the mean across 99 RTX-treated patients; derived from referenced publications (percent of patients with quantifiable B cells at indicated timepoints).

First 17 Patients Treated with AlloNK + RTX All Show Complete B-Cell Depletion Using

High Sensitivity Assay

Further, high-sensitivity analyses from the AlloNK clinical program indicate that the full treatment regimen, including lymphodepletion, AlloNK, and a CD20 monoclonal antibody, is required to achieve deep B-cell depletion. In a patient treated with AlloNK without a monoclonal antibody, B cells remained detectable throughout follow-up. Upon subsequent treatment with the full regimen, the same patient achieved complete B-cell depletion as measured by the high-sensitivity assay, sustained through at least four weeks.

Note: Preliminary data as of October 1, 2025 data cutoff; Preliminary data from ongoing autoimmune clinical trials: Phase 2a basket trial, Phase 1/1b trial in SLE/LN, investigator-initiated basket trial Reported numbers subject to change; Data plotted on log scale; values for C2D13 and C2D28 are zero

Note: Cy: cyclophosphamide; Flu: fludarabine; mAb: monoclonal antibody

B-cell depletion in one patient with autoimmune disease who received Cy / Flu + AlloNK as their first cycle and the full treatment regimen as their second cycle

Finally, evaluation of B-cell subpopulations at reconstitution in four patients treated with AlloNK plus rituximab demonstrated a predominance of naïve and transitional B cells, a pattern consistent with published observations following CD19-directed autologous CAR-T therapy and suggestive of immune reconstitution following deep B-cell depletion.

Note: No head-to-head trial has been conducted evaluating AlloNK against other data included herein. Differences exist between clinical trial design, patient populations and the product candidates/products themselves, and caution should be exercised when comparing data across trials

Note: Preliminary data as of October 1, 2025 data cutoff for patients treated with AlloNK + RTX in ongoing autoimmune trials. Reflects patients who have seen B-cell reconstitution since treatment. (n=4)

Note: BL: baseline; RC: reconstitution; RTX: rituximab

(1)Adapted from Mackensen et al 2022. Nature Medicine volume 28, 2124–2132

Increase in Naïve / Transitional B-Cells Following B-Cell Depletion with AlloNK + mAb Consistent with CD19 auto-CAR T Experience

B-NHL Readthrough to Autoimmune Disease

In the B-NHL setting, activity is also driven by deep depletion of B-cells, including cancerous B-cells in the periphery, and in the tissues where lesions are located, principally the lymphoid tissue. Peripheral B-cell levels can be measured in B-NHL patients, providing evidence of depletion of targeted cells in the periphery. CRs in B-NHL are assessed using the Lugano 2014 criteria which utilizes 18-fluorodeoxyglucose (FDG) PET/CT. CRs in B-NHL patients indicate disappearance of cancerous B-cells from lymphatic tissues, and therefore provide evidence that a therapy is targeting and eliminating cells of B-cell origin within tissues. An array of autoimmune diseases are driven by pathologic B-cells, and therefore, we believe observations of the pharmacodynamic response of a therapy or product candidate against cancerous B-cells in the periphery and in tissue in NHL patients can provide supporting evidence for the mechanism in autoimmune disease.

In the Phase 1 portion of this trial, as of October 22, 2025, in the fourteen patients who were naïve to CAR-T, the CRR was 64%, as determined by the Lugano 2014 criteria. The Lugano 2014 criteria is a widely accepted and published methodology used in clinical trials as well as in clinical practice for response assessment in lymphoma. The criteria recommend a combination of disease morphology assessment using CT and lesion metabolic activity assessment on PET, with PET metabolic assessments being the driver for overall response assessment. As of the October 22, 2025 data cutoff date, five of the nine patients with a CR had an ongoing response (meaning continuation of the CR at all follow-up points), with median DOR not reached, but at least 19.4 months. The longest responder remained progression free for at least 24 months after the start of treatment. We believe these data support that AlloNK in combination with B-cell targeted mAbs has the potential to provide deep B-cell depletion in common target tissues between B-NHL and autoimmune diseases and offer therapeutic potential, a differentiated safety profile and patient accessibility in numerous autoimmune diseases.

Early Evidence of Differentiated Safety Profile, Supporting Broadened Therapeutic Access

AlloNK is designed to lend itself to an improved experience for the patient following treatment and we believe this will broaden access to the community setting. This is in contrast to auto-CAR-T, where mandatory hospitalization is often required in order to observe for side-effects such as CRS and ICANS. We believe AlloNK has the potential to enable rheumatologists to treat patients in their own infusion centers as opposed to having to refer patients to tertiary care centers. In the first 32 autoimmune patients treated, as of an October 1, 2025 data cutoff, no CRS or ICANS was reported, and most treatment-emergent adverse events (TEAEs) were Grade 1 or 2, transient, and consistent with expected effects of Cy and Flu conditioning. Infection rates were similar to those observed with approved biologics for RA, and only one patient of the first 32 was hospitalized for an adverse event (a skin infection unrelated to AlloNK) in the 28-day window post treatment. All patients, as of this cutoff date, were treated as outpatients, and the majority were treated at community rheumatology trial sites with no specialized oncology oversight, demonstrating feasibility of AlloNK administration and patient management in the community setting. We believe this overall patient and physician experience and emerging tolerability profile are consistent with the treatment journey typically observed with intravenous mAb therapies.

The figure below shows the number of drug-related hospitalization days for the 30 days following dosing of AlloNK for all 32 autoimmune patients treated as of October 1, 2025.

Note: Preliminary data as of October 1, 2025 data cutoff, patients completed day 28 visit following first cycle with Cy / Flu + AlloNK + mAb; Data not cleaned and subject to change

Note: Cy: cyclophosphamide; Flu: fludarabine; mAb: monoclonal antibody; AE: adverse event; IV: intravenous; IIT: investigator initiated trial

• Protocol variances: AlloNK on d5 vs d6; first mAb dose on d1 vs d2; second mAb dose on d13 in company sponsored trial vs d15 in IIT, second dose of AlloNK in both at D13

** Protocol and practice variations: some patients had >6 infusion days due to separation of AlloNK and mAb dosing

Number of Hospitalization Days Due to Drug-related Adverse Events in 32 Patients Treated with AlloNK in Combination with anti-CD20 mAbs Across Three Ongoing Clinical Studies in Autoimmune Disease

As of the October 1, 2025 data cut-off, no treatment discontinuations were reported. There was one dose-limiting toxicity reported, consisting of persistent neutropenia beyond Day 28 in a patient who did not receive G-CSF supportive therapy. The patient was asymptomatic, and the neutropenia resolved spontaneously by approximately five weeks without intervention. Infection rates were low, with one reported Grade 3 infection during the evaluation period. Neutrophil and lymphocyte counts generally returned toward normal values by approximately Day 30 post-treatment. Many patients received prophylactic anti-infective therapy during the period of immunosuppression.

No CRS, no ICANS, and no requirement for tocilizumab have been reported to date with the AlloNK regimen. The safety profile observed thus far appears consistent with administration in a standard infusion setting and may support outpatient management, subject to continued clinical evaluation.

Note: No head-to-head trial has been conducted evaluating AlloNK against other data included herein. Differences exist between clinical trial design, patient populations and the product candidates/products themselves, and caution should be exercised when comparing data across trials

Note: Preliminary data as of October 1, 2025 data cutoff. for Cy / Flu + AlloNK + mAb from ongoing autoimmune clinical trials: Phase 2a basket trial, Phase 1/1b trial in SLE/LN, investigator-initiated basket trial

N.R.: Not Reported

Note: CRS: cytokine release syndrome; ICANS: immune effector cell-associated neurotoxicity syndrome; mAbs: monoclonal antibodies; RA: rheumatoid arthritis; IVIG: intravenous immunoglobulin

(1) Hagen et al ACR 2025. Abstract #0641 (2) Bucci et al ACR 2025. Abstract #0236 (3) Infection rates in USPI for Humira, Rinvoq, Orencia and Rituxan

AlloNK’s Tolerability Profile Observed to Date Compares Favorably to Autologous CAR-T and BCMA Targeted T-Cell Engagers

AlloNK Development in Autoimmune Diseases

AlloNK is an allogeneic, off-the-shelf, cryopreserved NK cell therapy candidate designed to enhance the ADCC effect of mAbs to drive B-cell depletion. AlloNK is designed to be administered in the community setting. Using our proprietary cell therapy manufacturing platform, we can generate thousands of doses of cryopreserved, infusion-ready AlloNK from a single cord blood unit.

We are currently evaluating AlloNK in three ongoing clinical studies. First, our Phase 2 basket study is testing combination with rituximab in RA, SjD, SSc and IIMs. We plan to prioritize further development of this combination in RA. AlloNK is also being investigated in combination with rituximab or obinutuzumab in a Phase 1/1b open-label multi-center clinical trial in patients with SLE with or without LN who previously failed treatment, for which the FDA has granted Fast Track designation to improve disease activity in patients with class III or class IV LN. In addition, an ongoing basket IIT is assessing the safety, tolerability and clinical activity of AlloNK in combination with rituximab in patients with RA, PV, GPA / MPA and SLE.

Our Phase 2 Basket Study, Prioritizing Clinical Development in RA

Our ongoing open-label Phase [2a] clinical study (NCT06991114) is evaluating the safety and preliminary efficacy of AlloNK, an allogeneic in combination with the anti-CD20 mAb rituximab in adults with relapsing forms of B-cell dependent rheumatologic diseases. The trial is designed as a single-group assignment and is recruiting approximately 90 adult participants with refractory RA, SjD, idiopathic inflammatory myopathies, or systemic sclerosis who have demonstrated inadequate response to prior therapies. The primary objective is to assess safety and tolerability of the combination regimen over the treatment period. Secondary objectives include evaluation of disease-specific efficacy endpoints at Week 52, such as changes in the Disease Activity Score 28 (DAS28-ESR) for RA, the Clinical European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (ClinESSDAI) for SjD, total improvement scores for myopathies, and the revised Composite Response Index in Systemic Sclerosis

(rCRISS). The general treatment schema used across our studies is outlined below. The lymphodepletion treatment regimen consists of three daily doses of 30 mg/m 2 fludarabine and a single dose of 1000 mg/m 2 cyclophosphamide, a very similar regimen as utilized in other cell therapy studies in oncology and autoimmune disease.

Treatment Regimen for AlloNK in Combination with Anti-CD20 mAbs in Our Ongoing Clinical Studies

AlloNK Clinical Development in Additional Indications

B-cell depletion has a therapeutic activity in multiple additional autoimmune indications as evidenced by indications where mABs targeted against CD20 such as rituximab and ocrelizumab are approved, as well as data from various auto CAR T studies in autoimmune disease.

Our open-label Phase 1 clinical study (NCT06265220) is evaluating AlloNK in combination with anti-CD20 mAbs (rituximab or obinutuzumab), following [lymphodepleting] chemotherapy, in adult subjects with relapsed or refractory lupus nephritis Class III or IV—with or without Class V—or other forms of refractory systemic lupus erythematosus. The trial is designed to enroll approximately 51 adults who have failed prior standard-of-care treatments. The primary objective is to assess the safety, tolerability and preliminary activity of the investigational regimen. Secondary assessments include overall health and response status following one or two treatment cycles spaced approximately 24 weeks apart. Participants receive lymphodepletion with cyclophosphamide and fludarabine prior to AB-101 administration, and treatment assignment may include AB-101 monotherapy or AB-101 combined with a B-cell depleting antibody.

The IIT (NCT06581562) is a basket trial, which is a clinical trial that evaluates how well a therapy works in patients with different diseases that share a common characteristic, such as different autoimmune indications. The basket design utilizes an initial safety run-in stage of nine all-comers patients with any of the four included indications, followed by expansion cohorts. The IIT will initially enroll patients with RA, PV, GPA / MPA and SLE. The primary objective of the clinical trial is to assess the safety, tolerability and preliminary activity of AlloNK in combination with rituximab. Primary efficacy endpoints specific to each indication (RA, PV, GPA / MPA and SLE) will be used. We also anticipate assessing translational biomarkers, including levels of autoantibodies relevant in each indication, serum complement levels, serum immunoglobulin isotypes, peripheral B-cell subsets, and peripheral levels of AlloNK for pharmacokinetic analysis. Treatment of the first patient in the basket IIT was initiated in August 2024.

Pursuant to an institution-initiated and sponsored clinical trial agreement with IRIS, we are providing support and supply AlloNK and funding for study-related expenses for the IIT, but unlike our sponsored clinical trials, IRIS is the regulatory sponsor of, and responsible for the conduct of the IIT. This IIT is not part of our clinical trials for AlloNK and data from this trial is reported by the relevant investigator. While we do not expect to be able to use the results from this IIT in our applications for marketing approval to the FDA or other comparable foreign regulatory agencies, we believe that this strategy may provide some competitive advantage as we will be able to acquire additional clinical insights beyond highly focused clinical trials in specific geographies and additional indications.

CAR-NK Programs

Our manufacturing platform also allows for the generation of CAR-targeted NK cells utilizing cord blood starting material with the same pre-selected characteristics and scale-up process as AlloNK. We own ex-APAC rights for AB-201, a HER2 targeting CAR-NK cell, and for AB-205, a CD5 directed CAR-NK.

AB-201

AB-201 is an allogeneic anti-HER2 CAR-NK cell product candidate, containing a CAR with a proprietary HER2 antigen recognition domain and expressing soluble IL-15. HER2, also known as Human Epidermal Growth Factor Receptor 2 or ErbB2, is a receptor tyrosine kinase that is overexpressed on many solid tumors, such as breast, gastric and esophageal, and bladder cancers. AB-201 has shown specific cytotoxic activity against HER2+ tumor cells in vitro and anti-tumor activity and tumor infiltration in vivo. AB-201 is designed to bind to a region distinct from other HER2-targeting drugs, such as trastuzumab and pertuzumab. We have received orphan drug designation for AB-201 in the United States.

It is estimated that there are over 50,000 patients diagnosed annually in the United States with tumors having high expression of HER2, with overexpression found in approximately 10% to 15% of breast cancer cases and in over 10% of bladder and esophageal cancers. Many breast cancer patients with HER2+ localized disease experience pathologic complete responses when treated with HER2-directed therapies. However, for patients who relapse and for those who present initially with metastatic disease, current treatments can provide clinical responses but are not curative, and prognosis generally worsens with each subsequent line of therapy. HER2 is expressed in a subset of gastric, gastro-esophageal junction and esophageal cancers. Each year, over 5,000 patients in the United States begin various lines of treatment for HER2+ disease. Trastuzumab and fam-trastuzumab deruxtecan are approved for use in HER2+ gastric cancer, but a significant unmet medical need remains with only about half of patients responding to these therapies in first-line treatment and fewer than 30% of patients responding in third and later lines. HER2 is also expressed in a subset of bladder cancers. Each year, over 5,000 bladder cancer patients in the United States receive treatment for cancer that expresses HER2, but there are no approved HER2-directed therapies in bladder cancer.

AB-205

AB-205 is an allogeneic anti-CD5 CAR-NK cell product candidate, containing a CAR with a CD5 antigen recognition domain and expressing soluble IL-15. CD5 is a T-cell activation marker and negative regulator of TCR signaling expressed on tumor cells in the majority of cases of T-cell lymphoma and leukemia. Our partner, GC Cell, has observed specific cytotoxic activity against CD5+ T-cell leukemia cell lines, CCRF-CEM and RPMI-8402, with AB-205 in vitro and meaningful anti-tumor activity in vivo.

CD5 is expressed in a large number of cases of T-cell lymphoma (TCL) and T-cell Acute Lymphoblastic Leukemia (T-ALL). TCL accounts for 10-15% of all NHL cases and is categorized as cutaneous (CTCL) or more aggressive PTCL forms. PTCL, which accounts for approximately half of TCL cases, can be further subdivided into subtypes, with an estimated 80% of all cases expressing CD5. The CD30-targeted antibody drug conjugate Adcetris (brentuximab vedotin, BV) is used in PTCL, with the highest efficacy in the anaplastic large cell lymphoma (ALCL) subtype which uniformly expresses CD30. However, approximately 15% of ALCL patients are refractory or quickly progress following BV, while another 50% of ALCL patients initially respond, but ultimately progress after BV. Further, efficacy of BV and expression of CD30 in other PTCL subtypes is varied. There remains an unmet need for effective and safe therapies in these populations.

CAR-NKs may be an especially advantageous construct for targeting cancers of T-cell origin because of two limitations of CAR-T cells. First, autologous CAR-T products must be generated from T-cells isolated by leukapheresis, and using cells from a patient as starting material may risk generating CAR-T product from cancerous T-cells which could result in secondary malignancy. Second, since CD5 is expressed on normal, activated T-cells, CAR-T products, whether autologous or allogeneic, may need to be engineered to avoid fratricide of CAR-T cells against other CAR-T cells.

Manufacturing Capabilities and Industrialization of NK Cell Therapy

We have a manufacturing-first approach, referencing the fact that even before we were founded, our strategic partner GC Cell had already invested years pioneering the manufacturing process that we use today. Unlike most other companies in the NK field who started clinical development before establishing a scalable manufacturing process, we started clinical development with a mature and robust process in place. Our process is designed to allow us to produce off-the-shelf, allogeneic NK cell therapy candidates at scale, with the mission to make these therapies broadly accessible for patients with devastating autoimmune diseases and cancers. We leveraged our deep expertise in NK cell biology to establish an end-to-end proprietary process in collaboration with our strategic partner, GC Cell.

We believe the following features of our platform provide multiple key advantages:

Cord Blood as the Donor Source of our NK Cell Product Candidates

Cord blood is a recognized source of healthy donor cells for hematopoietic stem cell transplants and is readily available from multiple public banks in the United States and Europe. NK cells make up 5% to 15% of peripheral blood lymphocytes. Traditionally, peripheral blood has been used as the source for NK cells for therapeutic use. However, studies conducted by GC Cell have shown that NK cells derived from cord blood have a nearly ten-fold greater potential for expansion in our proprietary culture systems than those derived from peripheral blood, without premature exhaustion. The expression of receptors of interest on the surface of NK cells, such as those involved in the activation of NK cells on engagement of tumor cells, was seen to be more consistent donor-to-donor for cord blood NKs than peripheral-blood NK cells. Our manufacturing process activates the NK cells in cord blood in a donor-independent manner, resulting in a highly scaled, active and consistent NK cell product.

Selection of Optimal Genetic Characteristics in the Donor Cord Blood Units

We pre-screen banked cord blood units for both the KIR-B haplotype and high-affinity variant of the CD16 receptor which are drivers of NK cell activity:

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KIR-B haplotype selection: We base our product candidates on cord blood units encoding KIR-B alleles of the KIR receptor family. It has been reported that KIR-B haplotype NK cells have more activating receptors than KIR-A. It has also been reported that acute myeloid leukemia patients receiving allogeneic transplants from homozygous KIR-B donors have significantly decreased relapse rates and increased disease-free survival than those receiving transplants from KIR-A donors.

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High-Affinity CD16 158V/V selection: We select cord blood units that have a variant of CD16 known as 158 V/V, which has been shown to lead to increased ADCC activity. In a clinical trial of rituximab, an anti-CD20 mAb, follicular lymphoma patients with the CD16 genotype encoding the 158 V/V allele had a significantly higher response rate compared to those with other CD16 genotypes.

Approximately 15% of cord blood units have the characteristics above. Following pre-selection, we ship the cord blood units to our manufacturing facility where they are held in cryostorage. We believe that the availability, quality, ability to prescreen and ease of logistics of cord blood make it the optimal donor cell source for our proprietary manufacturing process.

Established and Highly Scaled Proprietary Manufacturing Process

We are leveraging a manufacturing process designed to be cGMP-compliant and potentially optimized for highly scaled expansion of the NK cells from a cord blood unit using a proprietary culture system. The NK cells from selected cord blood units are expanded using a proprietary engineered feeder (eFeeder) cell culturing process. The eFeeder cells are engineered to express a combination of factors on their surface, which enhance the activation and expansion of NK cells from the cord blood unit. The eFeeder cells are manufactured in-house, irradiated and do not persist in the final product. This process has been developed to produce large numbers of mature and highly active NK and CAR-NK cells while avoiding overstimulation, which has been shown to lead to cellular senescence.

The NK cell expansion process consists of the following steps:

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ICB (Intermediate Cell Bank) production: The cord blood unit is thawed and depleted of T-cells before culturing with the eFeeder cells, resulting in a significant expansion and enrichment of NK cells. For CAR-NK product candidates, a lentivirus vector encoding the specific CAR construct and IL-15 can be introduced at this stage. This results in the generation of cryopreserved ICB which is then stored in vials. ICB samples are assessed for quality against qualified release specifications before use in the second expansion stage. For AlloNK, we routinely produce 50-80 vials of ICB from each cord blood unit. We have produced multiple ICBs from different donor cord blood units for each product candidate.

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Drug product production: A single vial of ICB is used to seed a second expansion step. This takes place in a 50-liter, single-use bioreactor and results in highly active, pure NK cells. The NK cells are harvested, vialed and cryopreserved. For AlloNK, we routinely produce >80 vials of one billion NK cells per vial for clinical use from each drug product batch. We have multiple bioreactors installed at our San Diego facility and have capacity to produce up to 60 batches per year. Samples of drug product from each batch are tested using qualified assays prior to release for clinical use.

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Product characterization: Our highly scaled and reproducible process for generating cord blood-derived NK and CAR-NK cells has yielded drug product that has consistently been observed to meet release specifications across manufacturing runs. For AlloNK, we and GC Cell have produced over 50 batches of drug product which passed all of our release criteria including criteria for purity, identity and functional activity.

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Effective cryopreservation: The effective long-term storage of cells while retaining product viability and potency is an essential step in providing off-the-shelf NK and CAR-NK cell therapies. The final step in the manufacturing process is cryopreservation. We believe that the ability to effectively cryopreserve our NK and CAR-NK cell therapy product candidates is a key differentiator for our platform and is essential to providing off-the-shelf products that can be shipped around the world and be available on demand for single or repeat patient dosing. Historically, NK cells have been reported to be highly sensitive to the stresses of a freeze-thaw cycle, and cryopreservation of NK cells has therefore been more challenging than T-cells. Our proprietary cryopreservation process uses methods that have consistently demonstrated >90% viability of our NK cells upon thawing, with no significant differences in NK cell activity or expression of cytokines, such as interferon-g and TNFa.

For AlloNK, at the current scale, each cord blood unit is expanded to yield 50 to 80 cryopreserved ICB units. In turn, each ICB unit is further expanded to yield 80 to 100+ one billion-cell drug product vials. The demonstrated expansion from a single cord blood unit is therefore over 4,000 one billion-cell vials which are enough to treat over 250 to 1,000 autoimmune patients assuming one billion to four billion AlloNK cells per dose and three doses for a treatment regimen of an aggregate of three billion to twelve billion AlloNK cells total per patient with autoimmune disease. To date, we and GC Cell have produced over 50 clinical batches of AlloNK, producing thousands of AlloNK vials at one billion cells per vial, and have performed release testing on drug product derived from eight different donors. We have demonstrated both batch-to-batch and donor-to-donor consistency.

Our Manufacturing Process Can Generate Thousands of Doses of AlloNK from a Single Cord Blood Unit

We are conducting an ongoing product stability study to assess the shelf-life of our NK cell product candidates. We have tested each batch of AlloNK for cell viability, identity, purity, sterility and potency. To date, we have demonstrated stable results at 48 months. Our cryopreservation process was designed using an infusion-ready media not only to ensure that the thawed cells retain high and consistent activity, but also to enable a simple thawing process in which the drug product does not require any further processing before administration.

Our Facility

In addition to the research and manufacturing capabilities at GC Cell’s headquarters in Korea, we have established full development and manufacturing facilities in San Diego, California. We have built a new 52,000-square-foot corporate headquarters, which includes research and process development laboratories, and have recruited a team of cell therapy experts driving discovery research, preclinical development, translational science, process and analytical development, and cell therapy manufacturing Our headquarters also includes a 9,000 square-foot purpose-built cGMP manufacturing center to support NK and CAR-NK cell production for our pipeline development and clinical trial supply. This new facility capacity is in addition to on-going CAR-NK manufacturing in Korea.

Our scaled manufacturing process established at GC Cell over more than ten years has enabled us to design an efficient layout for our San Diego manufacturing center that is cGMP compliant. Our facility comprises multiple production suites, a ICB / virus suite and a suite devoted to product fill-finish and cryopreservation. Each of the three 50L bioreactor suites dedicated to drug product production have the capacity to run 20 batches per year. Given drug product batches can yield more than 80-100 AlloNK vials with one billion NK cells each, our facility has the capacity to generate over 5,000 one billion NK cell vials per year.

Released finished product is stored off site at a third-party logistics vendor, as is currently the case for drug products manufactured for us by GC Cell. We intend to use our facility to enable new pipeline program research, development and manufacturing, to further optimize the AlloNK manufacturing process and produce AlloNK for current and future clinical trials and to supply any potential commercial launch.

Competition

The biopharmaceutical industry in general, and the cell therapy field in particular, is characterized by rapidly advancing and changing technologies, intense competition and a strong emphasis on intellectual property. We face substantial and increasing competition from large and specialty biopharmaceutical companies, as well as public and private medical research institutions and governmental agencies. Competitors may compete with us in hiring scientific and management personnel, establishing clinical study sites, recruiting patients to participate in clinical trials and acquiring technologies complementary to, or necessary for, our programs.

Our known biopharmaceutical competitors that are developing allogeneic NK, CAR-NK, or CAR-T cell therapies or T-cell engaging bispecific antibodies include, but may not be limited to, the following: Adicet Bio, Inc., Allogene Therapeutics, Inc., Amgen Inc., Artec Biotech, Inc., Autolus Therapeutics plc, Bristol-Myers Squibb Co, Cabaletta Bio, Inc., Capstan Therapeutics, Inc. (acquired by AbbVie), Candid Therapeutics, Inc., Caribou Biosciences, Inc., Cartesian Therapeutics, Inc., Celularity Inc., Century Therapeutics, Inc., Chimeric Therapeutics Ltd., Climb Bio, Inc., Coeptis Therapeutics Holdings, Inc., Cullinan Therapeutics Inc., Deverra Therapeutics Inc., Fate Therapeutics, Inc., Gamida Cell Ltd., Gilead Sciences, Inc., Glycostem Therapeutics B.V., Gracell Biopharmaceuticals, Inc. (acquired by AstraZeneca), GSK plc, iCell Gene Therapeutics Inc., ImmPACT Bio USA, Inc. (acquired by Lyell Immunopharma, Inc.), ImmunityBio, Inc., Indapta Therapeutics, Inc., Interius BioTherapuetics, Inc., ITabMed Co., Ltd., Johnson & Johnson, Kyverna Therapeutics, Inc., Luminary Therapeutics, Inc., Merck & Co., Inc., MiNK Therapeutics, Inc., Nkarta, Inc., NKGen Biotech, Inc., NÖK Therapeutics, Inc., Novartis AG, Orbital Therapeutics, Inc., Regeneron Pharmaceuticals, Inc., Roche, Rui Therapeutics Biotechnology Co., Ltd., Sana Biotechnology, Inc., Sanofi, Shoreline Biosciences Inc., Synthekine Inc., Takeda Pharmaceuticals Company Limited, UCI Therapeutics, Wugen, Inc. and Xencor, Inc.

Many of our current or potential competitors have significantly greater financial, technical and human resources, as well as more expertise in research and development, manufacturing, preclinical testing, conducting clinical studies and trials and commercializing and marketing approved products, than us. Mergers and acquisitions in the biopharmaceutical industry may result in even greater resource concentration among a smaller number of competitors. Smaller or early-stage companies may also prove to be significant competitors, either alone or through collaborative arrangements with large and established companies.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other comparable foreign regulatory authority approval for their products more rapidly than us, which could result in our competitors establishing a strong market position before we are able to enter the market. Key competitive factors affecting the success of all of our programs are likely to be their efficacy, safety, convenience, price and degree of reimbursement.

Intellectual Property

Intellectual property is of vital importance in our field and in biotechnology generally. Our commercial success depends in part on our ability to obtain intellectual property that protects our product candidates and combinations of our product candidates with other therapeutics. We seek to protect and enhance proprietary technology, inventions and improvements that are commercially important to the development of our business by seeking, maintaining and defending U.S. and foreign patent rights, whether developed internally or licensed from third parties.

We are actively building our intellectual property portfolio around our product candidates and our discovery programs, based on our own intellectual property and licensed intellectual property. One important step in building our current portfolio was executing the Core Agreement, described below, with GC Cell. The Core Agreement grants us an exclusive, royalty-bearing license, with the right to sublicense through multiple tiers, to certain intellectual property and technology owned or controlled by GC Cell relating to non-genetically modified and genetically modified NK cells, and culturing, engineering, and manufacturing thereof, to research, develop, manufacture, and commercialize NK cell pharmaceutical products anywhere in the world except for Asia, Australia and New Zealand (the Artiva Territory). Applications to date have been filed in the United States, Europe, Canada and Israel. Further, we intend to file patent applications relating to new technologies we develop, either ourselves or with our strategic partners. We also intend to continue to identify and license patents that provide protection and serve as an optimal platform to enhance our intellectual property and technology base.

Our current intellectual property estate is designed to provide multiple layers of protection, including (1) patent rights directed to innovative manufacturing processes and methods for generating therapeutic NK cells; (2) patent rights covering constructs for use in our CAR-NK candidates; and (3) patent rights covering methods of treatment for therapeutic indications using NK cells.

Our current patent portfolio as of March 1, 2026, includes seven patent families licensed from GC Cell that primarily relate to innovative manufacturing processes and methods for generating therapeutic NK cells. These families disclose compositions and methods used in NK cell manufacturing processes, as well as resulting products and therapeutic compositions, along with methods of treating cancer using these products and therapeutic compositions.

Our current patent estate as of March 1, 2026, includes three patent families licensed from GC Cell, three patent families we co-own with GC Cell, and one patent family that we own covering constructs for use in our CAR-NK programs. Two of the families we license from GC Cell relate to particular CAR components. The first of these includes one issued patent in the U.S. as well as pending applications in the United States, Europe, and Canada, and any patents that issue from these pending applications are expected to expire in 2037, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees; the second of these includes a pending application in the United States, and any patents that issue from this pending application are expected to expire in 2042, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees. The third family we license from GC Cell relates to a novel anti-HER2 antibody or antigen-binding fragment and includes four issued U.S. patents and pending applications in the United States, Europe, Canada, and Israel. The issued U.S. patents are expected to expire in 2038, and any patents that issue from the pending patent applications in these licensed families are expected to expire between 2038 and 2041, without accounting for potentially available patent term adjustments or extensions and assuming payment of appropriate maintenance, renewal, annuity or other fees. Two of the families we co-own with GC Cell relate to cells and constructs encoding IL-15 and a CAR utilizing the novel anti-HER2 antigen binding fragment we license from GC Cell and methods of treatment using these cells and constructs. The first of these families includes pending applications in the United States, Europe, Israel, and Canada, and any patents that issue from these pending applications are expected to expire in 2042, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees; the second of these families includes pending applications in the United States, Thailand, Singapore, Israel, Indonesia, Europe, China, Canada, and Australia, and any patents that issue from these pending applications are expected to expire in 2043, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees. The third family we co-own with GC Cell relates to our anti-CD19 CAR-NK cell products and includes pending applications in the United States and Europe; any patents that issue from these pending applications are expected to expire in 2042, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees. The patent family that we own relates to a novel antibody or antigen binding fragment and includes pending applications in the United States, Europe, and Korea. Although no patents have yet issued from this owned patent family, we expect the term of any patents that may issue from the pending patent applications in this family to extend to at least 2043, without accounting for potentially available patent term adjustments or extensions and assuming payment of appropriate maintenance, renewal, annuity or other governmental fees.

Our current patent estate as of March 1, 2026, includes ten patent families related to NK cells and to methods of treatment using NK cells in addition to a therapeutic antibody. The first family, which is co-owned by GC Cell and Incyte Corporation, relates to pharmaceutical combinations for treating tumors comprised of anti-CD19 antibody and NK cells. This family includes an issued patent in the U.S. and pending applications in Canada, Europe, Israel, the United States, Eurasia, Mexico, Ukraine, and South Africa; any patents that issue from these pending applications are expected to expire in 2039, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees. The second family, which we co-own with GC Cell, relates to the treatment of cancer with NK cells and a CD20 targeted antibody. This family includes pending applications in the United States, Europe, Canada, and Israel; any patents that issue from these pending applications are expected to expire in 2041, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees. The third, fourth, and fifth families, which we own, relate to the treatment of autoimmune indications with NK cells and therapeutic antibodies. The third family includes pending applications in the U.S., Europe, Korea, Japan, China, and Brazil; the fourth includes a pending PCT application; the fifth includes pending U.S. provisional applications; any patents that issue from these pending applications are expected to expire in 2044, 2045, and 2046, respectively, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees. The other five patent families, which we co-own with GC Cell, relate to NK cells and to additional combinations of NK cells and therapeutic antibodies directed to various targets. Of these, the first family includes pending applications in the United States, Europe, Canada, and Israel; any patents that issue from these pending applications are expected to expire in 2041, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees. The remaining families each include pending applications in the United States, Europe, Australia, China, Japan, and Korea; any patents that issue from these pending applications are expected to expire in 2042, without accounting for potentially available patent term adjustment or extensions, and assuming payment of appropriate maintenance, renewal, annuity, or other fees.

Our current patent estate as of March 1, 2026, also includes a patent family co-owned by us, Affimed GmbH and GC Cell related to therapeutic compositions and methods of treating cancer using NK cells in combination with one of Affimed’s innate cell engagers. This family includes pending applications in the United States, Australia, Canada, China, Europe, Israel, India, Japan, and Korea. We expect the term of any patents that issue from the pending patent applications in this family to extend until at least 2042, without accounting for potentially available patent term adjustment or extension and assuming payment of appropriate maintenance, renewal, annuity or other governmental fees.

With respect to both licensed and company-owned intellectual property, we cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our commercial products and methods of manufacturing the same.

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, the patent term is 20 years from the date of filing of the first non-provisional application to which priority is claimed. In the United States, patent term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S. Patent and Trademark Office (USPTO) in granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier-filed patent. In the United States, the term of a patent that covers an FDA-approved drug may also be eligible for a patent term extension of up to five years under the Drug Price Competition and Patent Term Restoration Act of 1984 (the Hatch-Waxman Act), which is designed to compensate for the patent term lost during the FDA regulatory review process. The length of the patent term extension is calculated based on the length of time it takes for regulatory review. A patent term extension under the Hatch-Waxman Act cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an approved drug may be extended. Moreover, a patent can only be extended once, and thus, if a single patent is applicable to multiple products, it can only be extended based on one product. Similar provisions are available in Europe and certain other foreign jurisdictions to extend the term of a patent that covers an approved drug. When possible, depending upon the length of clinical trials and other factors involved in the filing of a biologics license application (BLA), we expect to apply for patent term extensions for patents covering our product candidates and their methods of use.

In addition to patent protection, we also seek to rely on regulatory protection and exclusivities. For instance, we intend to rely on the 12-year period for marketing exclusivity in the United States, and similar marketing exclusivities in other countries, to prevent competitors from obtaining regulatory approval for our products.

We also rely on trademarks, trade secrets, know-how, continuing technological innovation, confidentiality agreements, and invention assignment agreements to develop and maintain our proprietary position. The confidentiality agreements are designed to protect our proprietary information and the invention assignment agreements are designed to grant us ownership of technologies that are developed for us by our employees, consultants, or other third parties. We seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems. While we have confidence in our agreements and security measures, either may be breached, and we may not have adequate remedies. In addition, our trade secrets may otherwise become known or independently discovered by competitors.

Our commercial success also depends in part on our ability to operate without infringing on the proprietary rights of others and to prevent others from infringing our proprietary rights.

Collaboration and License Agreements

GC Cell and Related Agreements

We have entered into several agreements with GC Cell and related entities concerning our platform NK cell technology and manufacturing of our core products, as described below.

In September 2019, we entered into an option and license agreement with GC Cell, as amended in June 2020 and February 2022 (Core Agreement). Under the Core Agreement, GC Cell granted us an exclusive, royalty-bearing license, with the right to sublicense through multiple tiers, under certain intellectual property and technology owned or controlled by GC Cell relating to non-genetically modified and genetically modified NK cells, and culturing, engineering, manufacturing thereof, to research, develop, manufacture and commercialize NK cell pharmaceutical products in the Artiva Territory. GC Cell retained rights under the license to allow it and its affiliates to perform obligations under the Core Agreement and other agreements between us and them.

Under the Core Agreement, GC Cell agreed to conduct a discovery, research, preclinical development and manufacturing program under a plan approved by a Joint Research Steering Committee (JSC), to generate and identify product candidates for nomination as option candidates. GC Cell will bear all costs for its work under the R&D Plan, except that we will bear all costs for completing IND-enabling activities performed by GC Cell on behalf of us, other than certain efficacy studies.

For each product candidate determined by the JSC to be an option candidate, we have an exclusive option under the Core Agreement to obtain an exclusive, sublicensable license to research, develop, manufacture and commercialize such candidate in the Artiva Territory for any therapeutic, prophylactic or diagnostic uses in humans, on economic terms to be determined in good faith by the parties. GC Cell retains exclusive rights to the licensed technology in Asia, Australia and New Zealand, though we have the right to request, and GC Cell has agreed to consider in good faith, inclusion of Australia, New Zealand and/or specific countries in Asia in the Artiva Territory on a product-by-product basis. If we elect not to exercise the option with respect to a particular option candidate, GC Cell retains the right to continue development of such candidate. To-date, we have exercised our rights to license four option candidates, including AlloNK (AB-101), AB-201 and AB-205.

We have control over and will bear the costs of the development, regulatory, manufacturing and commercialization activities relating to the option candidates for which we have exercised our option, each a licensed product. Accordingly, we have certain diligence obligations and must use commercially reasonable efforts to develop and seek regulatory approval for each licensed product in at least one indication in the United States and the EU, and following regulatory approval in a country, to commercialize such licensed product in at least one indication in such country. The Core Agreement provides that we have the right to engage GC Cell or its appropriate affiliate to provide research and manufacturing services for the licensed products being developed by us in the Artiva Territory under separately executed service agreements.

Under the Core Agreement, we are obligated to pay a low single-digit percentage royalty on net sales of any licensed products, the manufacture, use or sale of which is claimed by or uses any Core IP. The royalty rate is subject to reduction under certain scenarios, and royalties are payable on a product-by-product and country-by-country basis, beginning with the first commercial sale of a licensed product and continuing until the later of (i) expiration of the last-to-expire claim of the licensed patents and jointly owned patents in the country of sale; (ii) expiration of any regulatory exclusivity for a licensed product in that country; and (iii) the tenth anniversary of the first commercial sale of a licensed product in that country. We also have the exclusive option to extend our license to the Core IP to be worldwide with respect to products originated from us in exchange for a specified increase in the applicable royalty. GC Cell is also obligated to pay us a royalty at a rate equal to 50% of the royalty payable by us for such product in the Artiva Territory on net sales outside the Artiva Territory of any licensed product, the manufacture, use or sale of which is claimed by or uses any jointly owned intellectual property.

The Core Agreement will remain in effect until the expiration of the last-to-expire royalty payment obligations. The last to expire patents (or any patents that issue from pending applications) underlying the royalty payment obligations under the Core Agreement are currently expected to expire by 2042, without accounting for potentially available patent term extensions or adjustments. We have the right to terminate the Core Agreement for any reason upon 90 days’ written notice. Either party may terminate the Core Agreement upon the other party’s uncured material breach, bankruptcy or insolvency. Upon termination of the Core Agreement for any reason other than uncured material breach by GC Cell, we must (i) assign and transfer all regulatory materials and approvals relating to any licensed product to GC Cell, and (ii) grant GC Cell a right of reference and use to all pre-clinical and clinical data relating to any licensed product, except that both (i) and (ii) only apply to licensed products that were developed at least in part by GC Cell, or were developed by a third party, and are claimed by or use licensed GC Cell technology. If the Core Agreement is terminated by GC Cell due to an uncured material breach, bankruptcy or insolvency, sublicensees may receive a direct license from GC Cell.

In November 2019, we entered into a license agreement with GC Cell for our AB-101 product candidate, as amended in February 2022 (the AB-101 Agreement). AB-101 is the first product for which we exercised our option under the Core Agreement. Under the AB-101 Agreement, GC Cell granted us an exclusive, royalty-bearing license in the Artiva Territory, with the right to sublicense through multiple tiers, under certain intellectual property and technology owned or controlled by GC Cell, to research, develop, manufacture and commercialize AB-101.

Under the AB-101 Agreement, we are obligated to pay tiered royalties in the low-mid to high single-digit percentage range on annual net sales of any licensed AB-101 products. The royalty rate is subject to reduction under certain scenarios, and royalties are payable on a product-by-product and country-by-country basis, beginning with the first commercial sale of a licensed AB-101 product and continuing until the later of (i) expiration of the last-to-expire claim of the licensed patents and jointly owned patents in the country of sale; (ii) expiration of any regulatory exclusivity for a licensed product in that country; and (iii) the tenth anniversary of the first commercial sale of a licensed product in that country. We are also obligated to make milestone payments to GC Cell of (i) up to $22.0 million upon the first achievement of certain development milestones, and (ii) up to $55.0 million upon the first achievement of certain sales milestones. GC Cell is also obligated to pay us a royalty at a rate equal to 50% of the royalty payable by us for such product in the Artiva Territory on net sales outside the Artiva Territory of any licensed AB-101 product, the manufacture, use or sale of which is claimed by or uses any jointly owned intellectual property.

The AB-101 Agreement will remain in effect until the expiration of the last-to-expire royalty payment obligations. The last to expire patents (or any patents that issue from pending applications) underlying the royalty payment obligations under the AB-101 Agreement for AB-101 are currently expected to expire by 2042, without accounting for potentially available patent term extensions or adjustments. We have the right to terminate the AB-101 Agreement for any reason upon 90 days’ written notice. Either party may terminate the AB-101 Agreement upon the other party’s uncured material breach, bankruptcy or insolvency. Upon termination of the AB-101 Agreement for any reason other than uncured material breach by GC Cell, we must (i) assign and transfer all regulatory materials and approvals relating to AB-101 to GC Cell, and (ii) grant GC Cell a right of reference and use to all pre-clinical and clinical data relating to AB-101.

In October 2020, we entered into a license agreement with GC Cell for our AB-201 product candidate, as amended in February 2022 and September 2023 (the AB-201 Agreement). AB-201 is the second product for which we exercised our option under the Core Agreement. Under the AB-201 Agreement, GC Cell granted us an exclusive, royalty-bearing license in the Artiva Territory, with the right to sublicense through multiple tiers, under certain intellectual property and technology owned or controlled by GC Cell, to research, develop, manufacture and commercialize AB-201.

Under the AB-201 Agreement, we paid a one-time, upfront fee of $0.3 million as reimbursement of certain costs previously incurred by GC Cell relating to AB-201. We are obligated to pay tiered royalties in the mid to high single-digit percentage range on annual net sales of any licensed AB-201 products. The royalty rate is subject to reduction under certain scenarios, and royalties are payable on a product-by-product and country-by-country basis, beginning with the first commercial sale of a licensed AB-201 product and continuing until the later of (i) expiration of the last-to-expire claim of the licensed patents and jointly owned patents in the country of sale; (ii) expiration of any regulatory exclusivity for a licensed product in that country; and (iii) the tenth anniversary of the first commercial sale of a licensed product in that country. We are also obligated to make milestone payments to GC Cell of (i) up to $25.0 million upon the first achievement of certain development milestones, and (ii) up to $55.0 million upon the first achievement of certain sales milestones. GC Cell is also obligated to pay us a royalty at a rate equal to 50% of the royalty payable by us for such product in the Artiva Territory on net sales outside the Artiva Territory of any licensed AB-201 product, the manufacture, use or sale of which is claimed by or uses any jointly owned intellectual property. Further, in consideration of a grant-back license and right of reference to certain intellectual property rights and regulatory filings owned or controlled by us in the Artiva Territory for the exploitation of the AB-201 product outside the Artiva Territory, GC Cell is further obligated to pay us a low single-digit royalty on net sales outside the Artiva Territory of any licensed AB-201 product, as well as up to $1.8 million upon the first achievement of certain development milestones.

The AB-201 Agreement will remain in effect until the expiration of the last-to-expire royalty payment obligations. The last to expire patents (or any patents that issue from pending applications) underlying the payment obligations under the AB-201 Agreement are currently expected to expire by 2043, without accounting for potentially available patent term extensions or adjustments. We have the right to terminate the AB-201 Agreement for any reason upon 90 days’ written notice. Either party may terminate the AB-201 Agreement upon the other party’s uncured material breach, bankruptcy or insolvency. On termination of the AB-201 Agreement for any reason other than uncured material breach by GC Cell, we must (i) assign and transfer all regulatory materials and approvals relating to AB-201 to GC Cell, and (ii) grant GC Cell a right of reference and use to all pre-clinical and clinical data relating to AB-201.

In December 2022, we entered into a license agreement with GC Cell for our AB-205 product candidate (the AB-205 Agreement). AB-205 is the fourth product for which we exercised our option under the Core Agreement. Under the AB-205 Agreement, GC Cell granted us an exclusive, royalty-bearing license in the Artiva Territory, with the right to sublicense through multiple tiers, under certain intellectual property and technology owned or controlled by GC Cell, to research, develop, manufacture and commercialize AB-205.

Under the AB-205 Agreement, we paid to GC Cell a one-time, upfront payment of $1.0 million, and we are obligated to make a payment of $2.5 million to GC Cell after we notify GC Cell that we opt to proceed to clinical development with an AB-205 product. We are also obligated to pay tiered royalties in the mid to high single-digit percentage range on annual net sales of any licensed AB-205 products. The royalty rate is subject to reduction under certain scenarios, and royalties are payable on a product-by-product and country-by-country basis, beginning with the first commercial sale of a licensed AB-205 product and continuing until the later of (i) expiration of the last-to-expire claim of the licensed patents and jointly owned patents in the country of sale; (ii) expiration of any regulatory exclusivity for such licensed product in such country; and (iii) the tenth anniversary of the first commercial sale of such licensed product in such country. We are also obligated to make milestone payments to GC Cell of (i) up to $29.5 million upon the first achievement of certain development milestones, plus cost sharing of certain development costs incurred by GC Cell, and (ii) up to $28.0 million upon the first achievement of certain sales milestones. GC Cell is also obligated to pay us a royalty at a rate equal to 50% of the royalty payable by us for such product in the Artiva Territory on net sales outside the Artiva Territory of any licensed AB-205 product, the manufacture, use or sale of which is claimed by or uses any jointly owned intellectual property.

The AB-205 Agreement will remain in effect until the expiration of the last-to-expire royalty payment obligations. The last to expire patents (or any patents that issue from pending applications) underlying the royalty payment obligations under the AB-205 Agreement are currently expected to expire by 2043, without accounting for potentially available patent term extensions or adjustments. We have the right to terminate the AB-205 Agreement for any reason upon 90 days’ written notice. Either party may terminate the AB-205 Agreement upon the other party’s uncured material breach, bankruptcy or insolvency. Further, GC Cell may terminate the AB-205 Agreement if we do not elect to proceed with clinical development of the AB-205 Product after receipt of certain clinical data provided by GC Cell. Upon termination of the AB-205 Agreement for any reason other than uncured material breach by GC Cell, we must (i) assign and transfer all regulatory materials and approvals relating to AB-205 to GC Cell, and (ii) grant GC Cell a right of reference and use to all pre-clinical and clinical data relating to AB-205.

As contemplated by the Core Agreement, in August 2020 we entered into the GC Cell Research Services Agreement, as amended in February 2022, under which GC Cell agreed to provide research services in support of the research and development of one or more of the products we have licensed from GC Cell. The GC Cell Research Services Agreement provides that the parties will agree to specific projects as work orders under the GC Cell Research Services Agreement. Each work order shall set forth, upon terms mutually agreeable to GC Cell and us, the specific services to be performed by GC Cell, the timeline and schedule for the performance of the services and the compensation to be paid by us to GC Cell for the provision of such services, as well as any other relevant terms and conditions. Unless otherwise agreed by the parties in a work order, GC Cell will own all intellectual property generated in the course of its provision of services under the Agreement, and all such intellectual property, to the extent related to or arising from the licensed technology under the Core Agreement and selected product license agreements, including the AB-101 Agreement and the AB-201 Agreement, will be included in the licenses granted to us thereunder.

The GC Cell Research Services Agreement terminates on the five-year anniversary of its execution, except that GC Cell is obligated to complete any work orders that remain open at the time the agreement terminates. Both parties have the right to terminate the GC Cell Research Services Agreement for any reason upon 90 days’ written notice, though if GC Cell terminates the GC Cell Research Services Agreement without cause, then at our option the termination shall not be effective until the later of (a) the end of the 90-day notice period, or (b) the date on which the services provided under the open work order have been completed. Either party may terminate the GC Cell Research Services Agreement or any work order upon thirty (30) days’ written notice in the event of an uncured material breach. Either party may also terminate the GC Cell Research Services Agreement immediately in writing if the other party or its affiliates breaches the requirement that no individuals debarred or disqualified under the U.S. Federal Food, Drug and Cosmetic Act, or comparable applicable laws, may perform the services or use the data and intellectual property hereunder.

In March 2020, we entered into a Master Agreement for Manufacturing Services (the Manufacturing Agreement) with GC Cell, formerly GC Lab Cell Corporation, under which GC Cell agreed to manufacture specified products under individual work orders for use in our Phase 1 and Phase 2 clinical trials. Each work order will contain an estimated budget of service fees and out-of-pocket costs to be incurred in the performance of services under the agreement and the work order, as well as additional terms and conditions relating to the estimated budget. We will own all results and data generated by GC Cell under the Manufacturing Agreement. GC Cell may not subcontract its performance, even to affiliates, without our written consent.

Under the Manufacturing Agreement, we granted GC Cell a limited non-exclusive, non-transferable, non-sublicensable, revocable, royalty-free license to our pre-existing intellectual property that is necessary and useful to manufacture products for us. Any intellectual property generated in the course of the manufacturing will be owned by us. GC Cell granted us a limited worldwide, royalty-free, fully paid, non-exclusive license, including the right to sublicense through multiple tiers, to GC Cell background technology and improvements thereof used to manufacture products under the agreement. These licenses survive termination of the Manufacturing Agreement.

The Manufacturing Agreement expires on the five-year anniversary of its execution, unless terminated earlier or extended by the parties in writing. Under the terms of the Manufacturing Agreement, as amended in July 2020, we have the right to terminate the Manufacturing Agreement at any time and for any reason upon six (6) months written notice. We also have the right to terminate any open work order at any time and for any reason upon sixty (60) days’ written notice. Either party may terminate the Manufacturing Agreement or any work order upon thirty (30) days’ written notice in the event of an uncured material breach. GC Cell may terminate any work order on sixty (60) days’ prior written notice if GC Cell reasonably concludes that it is not technically or scientifically feasible to deliver the services contemplated by such work order despite applying its commercially reasonable efforts, but only if (i) such non-feasibility is not caused by GC Cell and is outside of GC Cell’s reasonable control and (ii) the parties are unable to resolve such scientific or technical issues within a sixty (60) day period.

Affimed Collaboration Agreement

In November 2022, we entered into a collaboration agreement (the Affimed Collaboration Agreement) with Affimed, as amended in November 2022 and June 2023. The collaboration focused on the clinical development and commercialization of a combination therapy comprising (i) Affimed’s product acimtamig and (ii) our product AlloNK in the United States and certain other countries that we and Affimed may agree to include, excluding specified Asia Pacific region countries (the Territory) for any and all uses in humans and animals, with an initial focus on the treatment of CD30+ Hodgkin Lymphoma and Peripheral T-Cell Lymphoma and other indications included in a development plan.

Under the Affimed Collaboration Agreement, Affimed was primarily responsible for the development of the combination therapy, the conduct of the relevant clinical trials and the preparation and filing of regulatory materials during the clinical development. We agreed to support Affimed in the development, in particular through the supply of AlloNK and our IL-2 product to be used in the clinical trials. Affimed would have the sole right and responsibility to promote the combination therapy according to a jointly aligned promotion plan.

In May 2025, Affimed filed for insolvency and in July 2025, we terminated the Affimed Collaboration Agreement.

Sales and Marketing

Given our stage of development, we have not yet established a commercial organization or distribution capabilities. We intend to build a commercial infrastructure to support sales of any of our approved products. We expect to manage sales, marketing and distribution through internal resources and third-party relationships. While we may commit significant financial and management resources to commercial activities, we will also consider collaborating with one or more pharmaceutical companies to enhance our commercial capabilities.

Government Regulation and Product Approval

As a biopharmaceutical company that operates in the United States, we are subject to extensive regulation. Our cell products will be regulated as biologics. With this classification, commercial production of our products will need to occur in registered facilities in compliance with cGMP for biologics. The FDA categorizes human cell- or tissue-based products as either minimally manipulated or more than minimally manipulated and has determined that more than minimally manipulated products require clinical trials to demonstrate product safety and efficacy and the submission of a BLA for marketing authorization. Our products are considered more than minimally manipulated and will require evaluation in clinical trials and the submission and approval of a BLA before we can market them.

Government authorities in the United States, at the federal, state and local levels, and in other countries extensively regulate, among other things, the research, development, testing, manufacturing, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of biopharmaceutical products such as those we are developing. Our product candidates must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory authorities before they may be legally marketed in foreign countries. Generally, our activities in other countries will be subject to regulation that is similar in nature and scope as that imposed in the United States, although there can be important differences. Additionally, some significant aspects of regulation in the European Union (EU) are addressed in a centralized way, but country-specific regulation remains essential in many respects. The process for obtaining regulatory marketing approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

U.S. Product Development Process

In the United States, the FDA regulates pharmaceutical and biological products under the Federal Food, Drug and Cosmetic Act (FDCA), the Public Health Service Act (PHSA) and their implementing regulations. 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. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval, may subject an applicant to administrative or judicial sanctions. FDA sanctions could include, among other actions, refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls or withdrawals from the market, product seizures, total or partial suspension of production or distribution injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us. The process required by the FDA before a biological product may be marketed in the United States generally involves the following:

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completion of nonclinical laboratory tests and animal studies according to good laboratory practices (GLPs) and applicable requirements for the humane use of laboratory animals or other applicable regulations;

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submission to the FDA of an IND, which must become effective before human clinical trials may begin;

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approval by an independent Institutional Review Board (IRB) or ethics committee at each clinical site before the trial is commenced;

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performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as good clinical practices (GCPs), and any additional requirements for the protection of human research patients and their health information, to establish the safety and efficacy of the proposed biological product for its intended use;

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submission to the FDA of a BLA for marketing approval that includes substantial evidence of safety, purity and potency from results of nonclinical testing and clinical trials;

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

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satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the biological product is produced to assess compliance with cGMP, to assure that the facilities, methods and controls are adequate to preserve the biological product’s identity, strength, quality and purity and, if applicable, the FDA’s current good tissue practices (GTPs), for the use of human cellular and tissue products;

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potential FDA audit of the nonclinical study and clinical trial sites that generated the data in support of the BLA; and

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FDA review and approval, or licensure, of the BLA.

Before testing any biological product candidate, including our product candidates, in humans, the product candidate enters the preclinical testing stage. Preclinical tests, also referred to as nonclinical studies, include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the product candidate. The conduct of the preclinical tests must comply with federal regulations and requirements including GLPs. The clinical trial sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. Some preclinical testing may continue even after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions regarding the proposed clinical trials and places the trial on a clinical hold within that 30-day time period. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. The FDA may also impose clinical holds on a biological product candidate at any time before or during clinical trials due to safety concerns or non-compliance. If the FDA imposes a clinical hold, trials may not recommence without FDA authorization and then only under terms authorized by the FDA. Accordingly, we cannot be sure that submission of an IND will result in the FDA allowing clinical trials to begin, or that, once begun, issues will not arise that suspend or terminate such trials.

Clinical trials involve the administration of the biological product candidate to patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety, including stopping rules that assure a clinical trial will be stopped if certain adverse events should occur. Each protocol and any amendments to the protocol must be submitted to the FDA as part of the IND. Clinical trials must be conducted and monitored in accordance with the FDA’s regulations comprising the GCP requirements, including the requirement that all research patients provide informed consent. Further, each clinical trial must be reviewed and approved by an independent IRB at or servicing each institution at which the clinical trial will be conducted. An IRB is charged with protecting the welfare and rights of trial participants and considers such items as whether the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the form and content of the informed consent that must be signed by each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed. Certain clinical trials involving human gene transfer research also must be overseen by an Institutional Biosafety Committee, a standing committee established specifically to provide peer review of the safety of research plans, procedures, personnel training and environmental risks of work involving recombinant DNA molecules. IBCs are typically assigned certain review responsibilities relating to the use of recombinant DNA molecules, including reviewing potential environmental risks, assessing containment levels, and evaluating the adequacy of facilities, personnel training and compliance with the NIH Guidelines. Some studies also include oversight by an independent group of qualified experts organized by the clinical study 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 studies and clinical study results to public registries.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

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Phase 1. The biological product is initially introduced into healthy human subjects and tested for safety. In the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing is often conducted in patients.

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

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Phase 3. Clinical trials are undertaken to further evaluate dosage, clinical efficacy, 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.

Post-approval clinical trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up. During all phases of clinical development, regulatory authorities require extensive monitoring and auditing of all clinical activities, clinical data and clinical trial investigators. Annual progress reports detailing the results of the clinical trials must be submitted to the FDA. Written IND safety reports must be promptly submitted to the FDA, and the investigators for serious and unexpected adverse events, any findings from other studies, tests in laboratory animals or in vitro testing that suggest a significant risk for human patients, or any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting. The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all. The FDA or the sponsor or its data safety monitoring board may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research patients are being exposed to an unacceptable health risk, including risks inferred from other unrelated immunotherapy trials. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the biological product has been associated with unexpected serious harm to patients.

Human immunotherapy products are a new category of therapeutics. Because this is a relatively new and expanding area of novel therapeutic interventions, there can be no assurance as to the length of the trial period, the number of patients the FDA will require to be enrolled in the trials in order to establish the safety, efficacy, purity and potency of immunotherapy products, or that the data generated in these trials will be acceptable to the FDA to support marketing approval.

Concurrently with clinical trials, companies usually complete additional studies and must also develop additional information about the physical characteristics of the biological product as well as 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, the sponsor must develop methods for testing the identity, strength, quality, potency and purity of the final biological product. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the biological product candidate does not undergo unacceptable deterioration over its shelf life.

U.S. Review and Approval Processes

After the completion of clinical trials of a biological product, FDA approval of a BLA must be obtained before commercial marketing of the biological product. The BLA submission must include results of product development, laboratory and animal studies, human trials, information on the manufacture and composition of the product, proposed labeling and other relevant information. The testing and approval processes require substantial time and effort and there can be no assurance that the FDA will accept the BLA for filing and, even if filed, that any approval will be granted on a timely basis, if at all.

Under the Prescription Drug User Fee Act (PDUFA), as amended, each BLA must be accompanied by a significant user fee. The FDA adjusts the PDUFA user fees on an annual basis. PDUFA also imposes an annual program fee for biological products. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business. Additionally, no user fees are assessed on BLAs for products designated as orphan drugs, unless the product also includes a non-orphan indication.

Within 60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the agency accepts it for filing. The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information. In this event, the BLA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the BLA. The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, potent, and/or effective for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, safety, strength, quality, potency and purity. The FDA may refer applications for novel biological products or biological products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. During the biological product approval process, the FDA also will determine whether a Risk Evaluation and Mitigation Strategy (REMS), is necessary to assure the safe use of the biological product. A REMS is a safety strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS. The FDA will not approve a BLA without a REMS, if required. Before approving a BLA, the FDA will inspect the facilities at which the product is manufactured. The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. For immunotherapy products, the FDA also will not approve the product if the manufacturer is not in compliance with the GTPs, to the extent applicable. These are FDA regulations and guidance documents that govern the methods used in, and the facilities and controls used for, the manufacture of human cells, tissue and cellular and tissue based products (HCT/Ps), which are human cells or tissue intended for implantation, transplant, infusion, or transfer into a human recipient. The primary intent of the GTP requirements is to ensure that cell and tissue-based products are manufactured in a manner designed to prevent the introduction, transmission and spread of communicable disease. FDA regulations also require tissue establishments to register and list their HCT/Ps with the FDA and, when applicable, to evaluate donors through screening and testing. Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure that the clinical trials were conducted In compliance with IND trial requirements and GCP requirements. To assure cGMP, GTP and GCP compliance, an applicant must incur significant expenditure of time, money and effort in the areas of training, record keeping, production and quality control.

Notwithstanding the submission of relevant data and information, the FDA may ultimately decide that the BLA does not satisfy its regulatory criteria for approval and deny approval. Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently than we interpret the same data. If the agency decides not to approve the BLA in its present form, the FDA will issue a complete response letter that describes all of the specific deficiencies in the BLA identified by the FDA. The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring additional clinical trials. Additionally, the complete response letter may include recommended actions that the applicant might take to place the application in a condition for approval. If a complete response letter is issued, the applicant may either resubmit the BLA, addressing all of the deficiencies identified in the letter, or withdraw the application.

If a product receives regulatory approval, the approval may be limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product. Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling. The FDA may impose restrictions and conditions on product distribution, prescribing, or dispensing in the form of a risk management plan, or otherwise limit the scope of any approval. In addition, the FDA may require post marketing clinical trials, sometimes referred to as Phase 4 clinical trials, designed to further assess a biological product’s safety and effectiveness, and testing and surveillance programs to monitor the safety of approved products that have been commercialized.

In addition, under the Pediatric Research Equity Act (PREA), as amended, a BLA or supplement to a BLA must contain data to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDCA requires that a sponsor of a biological product or drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit a pediatric study plan to the FDA not later than 60 days after the end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA. The FDA may grant deferrals for submission of data or full or partial waivers. Generally, PREA does not apply to any product for an indication for which orphan designation has been granted. However, if only one indication for a product has orphan designation, a pediatric assessment may still be required for any applications to market that same product for the non-orphan indication(s).

Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States. and for which there is no reasonable expectation that the cost of developing and making available in the United States. a drug or biologic for this type of disease or condition will be recovered from sales in the United States. for that drug or biologic. Orphan drug designation must be requested before submitting a BLA. 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. The orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review or approval process.

If a product that has orphan drug designation subsequently receives the first FDA approval 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, to market the same biologic 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. Orphan drug exclusivity does not prevent 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, exclusive marketing rights in the United States 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.

Expedited Development and Review Programs

The FDA has a fast track program that is intended to expedite or facilitate the process for reviewing new products that meet certain criteria. Specifically, new products are eligible for fast track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. Fast track designation applies to the combination of the product and the specific indication for which it is being studied. Unique to a fast track product, the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.

Any product, submitted to the FDA for approval, including a product with a fast track designation, may also be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated approval. A product is eligible for priority review if it has the potential to provide safe and effective therapy where no satisfactory alternative therapy exists or a significant improvement in the treatment, diagnosis or prevention of a disease compared to marketed products. The FDA will attempt to direct additional resources to the evaluation of an application for a new product designated for priority review in an effort to facilitate the review.

Additionally, depending on the design of the applicable clinical studies, a product may be eligible for accelerated approval. In particular, products studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product has an effect on 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. As a condition of approval, the FDA may require that a sponsor of a drug or biological product receiving accelerated approval perform adequate and well-controlled post-marketing clinical studies and may require such confirmatory studies to be underway prior to granting any accelerated approval. In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

In addition, breakthrough therapy designation is intended to expedite the development and review of products that treat serious or life-threatening conditions. The designation by FDA requires preliminary clinical evidence that a product candidate, alone or in combination with other drugs and biologics, demonstrates substantial improvement over currently available therapy on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. If the FDA designates a breakthrough therapy, it may take actions appropriate 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 drug 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 trials or more efficient trials that require less time to complete and may minimize the number of patients exposed to a potentially less efficacious treatment. Breakthrough therapy designation comes with all of the benefits of fast track designation, which means that the sponsor may submit sections of the BLA for review on a rolling basis if certain conditions are satisfied, including an agreement with FDA on the proposed schedule for submission of portions of the application and the payment of applicable user fees before the FDA may initiate a review. The breakthrough therapy designation is a distinct status from both accelerated approval and priority review, which can also be granted to the same product if relevant criteria are met. If a product is designated as breakthrough therapy, FDA will expedite the development and review of such product. Fast Track designation, priority review and breakthrough therapy designation do not change the standards for approval but may expedite the development or approval process.

Post-Approval Requirements

Any products for which we receive FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, and complying with FDA promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses (known as “off-label use”), limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the internet. Although a physician may prescribe a legally available product for an off-label use, if the physicians deems such product to be appropriate in his/her professional medical judgment, a manufacturer may not market or promote off-label uses. However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA approved labeling. A company that is found to have promoted off-label use of its product may be subject to significant liability, including administrative, civil and criminal sanctions.

In addition, quality control and manufacturing procedures must continue to conform to applicable manufacturing requirements after approval to ensure the long-term stability of the product. 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. Manufacturers and other entities involved in the manufacture and distribution of approved products 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. Discovery of problems with a product after approval may result in restrictions on a product, manufacturer, or holder of an approved BLA including, among other things, recall or withdrawal of the product from the market. In addition, changes to the manufacturing process are strictly regulated, and depending on the significance of the change, may require prior FDA approval before being implemented. Other types of changes to the approved product, such as adding new indications and claims, are also subject to further FDA review and approval.

The FDA also may require post-marketing testing, known as Phase 4 testing, and surveillance to monitor the effects of an approved product. Discovery of previously unknown problems with a product or the failure to comply with applicable FDA requirements can have negative consequences, including adverse publicity, judicial or administrative enforcement, warning letters from the FDA, mandated corrective advertising or communications with doctors, and civil or criminal penalties, among others. Newly discovered or developed safety or effectiveness data may require changes to a product’s approved 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 approval of our products under development.

U.S. Marketing Exclusivity

The Biologics Price Competition and Innovation Act (BPCIA), amended the PHSA to authorize the FDA to approve similar versions of innovative biologics, commonly known as biosimilars. A competitor seeking approval of a biosimilar must file an application to establish its molecule as highly similar to an approved innovator biologic, among other requirements. The BPCIA, however, bars the FDA from approving biosimilar applications for 12 years after an innovator biological product receives initial marketing approval. This 12-year period of data exclusivity may be extended by six months, for a total of 12.5 years, if the FDA requests that the innovator company conduct pediatric clinical investigations of the product.

Depending upon the timing, duration and specifics of the FDA approval of the use of our product candidates, some of our U.S. patents, if granted, may be eligible for limited patent term extension under the Hatch-Waxman Act. The Hatch-Waxman Act permits a patent restoration term of up to five years, as compensation for patent term lost during product development and the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date. The patent term restoration period is generally one-half the time between the effective date of an IND and the submission date of a BLA plus the time between the submission date of a BLA and the approval of that application. Only one patent applicable to an approved product is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent. The U.S. Patent and Trademark Office, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration. In the future, we may intend to apply for restoration of patent term for one of our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA.

Pediatric exclusivity is another type of regulatory market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial.

Other U.S. Healthcare Laws and Compliance Requirements

In the United States, our activities are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including but not limited to, the Centers for Medicare & Medicaid Services (CMS), other divisions of the U.S. Department of Health and Human Services (HHS), for example, the Office of Inspector General, the U.S. Department of Justice (DOJ) and individual U.S. Attorney offices within the DOJ, and state and local governments. For example, our business practices, including our research and any future sales, marketing and scientific/educational grant programs may be required to comply with federal anti-kickback and fraud and abuse laws, the false claims laws, the data privacy and security provisions of the Health Insurance Portability and Accountability Act (HIPAA), federal transparency requirements and similar state laws, each as amended.

The federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any remuneration, including any kickback, bribe or rebate, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for, either the referral of an individual for, or the purchasing, leasing, ordering or arranging for the purchase, lease or order of any item or service reimbursable, in whole or in part, under Medicare, Medicaid or other federal healthcare programs. The term remuneration has been interpreted broadly to include anything of value. The federal Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers and formulary managers on the other. Additionally, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. Rather, if “one purpose” of the remuneration is to induce referrals, the federal Anti-Kickback Statute is violated. 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 and require strict compliance in order to offer protection. Practices that involve remuneration that may be alleged to be intended to induce prescribing, purchasing or recommending 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 federal Anti-Kickback Statute. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances. Our practices may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor.

The federal civil monetary penalties statute imposes penalties against any person or entity who, among other things, is determined to have knowingly presented or caused to be presented a false or fraudulent claim to, among others, a federal healthcare program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent.

The federal civil False Claims Act (FCA) prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to, or approval by, the federal government or knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government in order to avoid, decrease or conceal an obligation to pay money to the federal government. As a result of a modification made by the Fraud Enforcement and Recovery Act of 2009, a claim includes “any request or demand” for money or property presented to the federal government. Pharmaceutical and other healthcare companies are being investigated or, in the past, have been prosecuted under these laws for, among other things, allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. In addition, pharmaceutical and other healthcare companies also have been prosecuted for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus non-reimbursable, uses. Moreover, a claim that includes items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA.

HIPAA created additional federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme or artifice to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device, 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. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

We may be subject to data privacy and security regulations by both the federal government and the states in which we conduct our business. For example, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (HITECH), and their implementing regulations, imposes requirements on certain types of individuals and entities, including covered entities, for example, certain healthcare providers, health plans and healthcare clearinghouses, and their respective business associates that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity and their subcontractors that use, disclose, access, or otherwise process individually identifiable protected health information, relating to the privacy, security and transmission of individually identifiable health information. In addition, state laws govern the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

Additionally, the federal Physician Payments Sunshine Act and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with certain exceptions, annually report information to CMS related to certain payments or other transfers of value made or distributed to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (such as physician assistants and nurse practitioners) and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals and to report annually certain ownership and investment interests held by physicians and their immediate family members.

Also, many states have similar fraud and abuse statutes or regulations similar to the aforementioned federal laws that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor. In order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of drug and biological products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state. Some states also impose requirements on manufacturers and distributors to establish the pedigree of product in the chain of distribution, including some states that require manufacturers and others to adopt new technology capable of tracking and tracing product as it moves through the distribution chain. Several states and local jurisdictions have enacted legislation requiring pharmaceutical and biotechnology companies to establish marketing compliance programs and comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data to pharmaceutical and biotechnology companies for use in sales and marketing, and to prohibit certain other sales and marketing practices. All of our activities are potentially subject to federal and state consumer protection and unfair competition laws.

If our operations are found to be in violation of any of the federal and state healthcare laws described above or any other governmental regulations that apply to us, we may be subject to significant penalties, including without limitation, civil, criminal and/or administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participation in government programs, such as Medicare and Medicaid, injunctions, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, additional reporting requirements and/or oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

Data Privacy and Security Laws

We are and may in the future become subject to numerous state, federal and foreign laws, regulations and standards that govern the collection, use, access to, confidentiality, security, and other processing of health-related and other personal information. In the United States, such obligations include, without limitation various federal and state laws and regulations, including data breach notification laws, health information privacy and security laws, and consumer protection laws and regulations.

Numerous U.S. states have enacted comprehensive consumer privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording state residents with certain rights concerning their personal data. As applicable, such rights may include the right to access, correct, or delete certain personal data, and to opt-out of certain data processing activities, such as targeted advertising, profiling, and automated decision-making. The exercise of these rights may impact our business and ability to provide our products and services. Certain states also impose stricter requirements for processing certain types of personal data, including sensitive information, such as conducting data privacy impact assessments. These state laws allow for statutory fines for noncompliance. For example, the California Consumer Privacy Act of 2018 (the CCPA) applies to personal data of consumers, business representatives, and employees who are California residents and provides for fines and allows private litigants affected by certain data breaches to recover significant statutory damages.

Outside the United States, under foreign laws, such as the General Data Protection Regulation, companies may face temporary or definitive bans on personal data processing and other corrective actions; fines of up to 20 million Euros under the European Union’s General Data Protection Regulation 2016/679 (EU GDPR), 17.5 million pounds sterling under the EU GDPR as it forms part of United Kingdom law by virtue of section 3 of the European Union (Withdrawal) Act 2018, or, in each case, 4% of annual global revenue, whichever is greater; or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests. See the section titled “Risk Factors – Risks Related to Government Regulation” for additional information about the laws and regulations to which we may become subject and about the risks to our business associated with such laws and regulations.

Coverage, Pricing and Reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we obtain regulatory approval. In the United States and certain markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend, in part, on the extent to which third-party payors provide coverage, and establish adequate reimbursement levels for such products. No uniform policy for coverage and reimbursement exists in the United States, and coverage and reimbursement can differ significantly from payor to payor. As a result, the coverage determination process is often time-consuming and costly.

In the United States, third-party payors include federal and state healthcare programs, private managed care providers, health insurers and other organizations. The process for determining whether a third-party payor will provide coverage for a product may be separate from the process for setting the price of a product or from establishing the reimbursement rate that such a payor will pay for the product. Third-party payors may limit coverage to specific products on an approved list, also known as a formulary, which might not include all of the FDA-approved products for a particular indication. Third-party payors are increasingly challenging the price, examining the medical necessity and reviewing the cost-effectiveness of medical products, therapies and services, in addition to questioning their safety and efficacy. We may need to conduct expensive pharmaco-economic studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain the FDA approvals. Our product candidates may not be considered medically necessary or cost-effective. A payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved. Further, one payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage for the product. Further, coverage policies and third-party payor reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained more products for which we receive marketing approval, less favorable coverage policies and reimbursement rates may be implemented in the future. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development. Additionally, any companion diagnostic test that we develop will be required to obtain coverage and reimbursement separate and apart from the coverage and reimbursement we seek for our product candidates, if approved.

Further, the containment of healthcare costs has become a priority of foreign and domestic governments as well as private third-party payors. The pricing of drugs has been a focus in this effort. Governments and private third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. For example, the U.S. Department of Health and Human Services (HHS) imposes rebates on many Medicare Part B and Medicare Part D products to penalize price increases that outpace inflation on an annual basis. HHS has also been empowered to negotiate the price of certain single-source biologics that have been on the market for at least eleven (11) years covered under Medicare as part of the Medicare Drug Price Negotiation Program. Each year up to twenty (20) products will be selected by HHS for the Medicare Drug Price Negotiation Program. Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

Different pricing and reimbursement schemes exist in other countries. In the EU, governments influence the price of pharmaceutical products through their pricing and reimbursement rules and control of national health care systems that fund a large part of the cost of those products to consumers. Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement price has been agreed. To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials that compare the cost-effectiveness of a particular product candidate to currently available therapies. Other member states allow companies to fix their own prices for medicines, but monitor and control company profits. The downward pressure on health care costs has become very intense. As a result, increasingly high barriers are being erected to the entry of new products. In addition, in some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country. Accordingly, in markets outside the United States, the reimbursement for our products may be reduced compared with the United States and may be insufficient to generate commercially reasonable revenue and profits.

The marketability of any product candidates for which we receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement. In addition, emphasis on managed care in the United States has increased and we expect will continue to increase the pressure on healthcare pricing. Coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Healthcare Reform

In the United States and some foreign jurisdictions, there have been, and continue to be, several legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of product candidates, restrict or regulate post-approval activities, and affect the ability to profitably sell product candidates for which marketing approval is obtained. Among policy makers and payors in the United States 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 United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.

For example, the Affordable Care Act has substantially changed healthcare financing and delivery by both governmental and private insurers. Since its enactment, there have been amendments and judicial, Congressional and executive branch challenges to certain aspects of the Affordable Care Act. For example, on July 4, 2025, the One Big Beautiful Bill Act (the OBBBA) was signed into law, which narrowed access to Affordable Care Act marketplace exchange enrollment and declined to extend the Affordable Care Act enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance. The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program. Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies.

Other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. These changes include aggregate reductions to Medicare payments to providers of 2% per fiscal year, which began in 2013 and will remain in effect until 2032 unless additional Congressional action is taken.

The current administration is pursuing policies to reduce regulations and expenditures across government agencies including at HHS, the FDA, CMS and related agencies. These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business. For example, the current administration has announced agreements with several pharmaceutical companies that require the drug manufacturers to offer, through a direct to consumer platform (TrumpRx) U.S. patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues. Other recent actions, for example, include (1) directing agencies to reduce agency workforce and cut programs; (2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives; (3) imposing tariffs on imported pharmaceutical products; and (4) as part of the Make America Healthy Again (MAHA) Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising. Additionally, the current administration recently called on Congress to enact “The Great Healthcare Plan,” to codify and expand Most-Favored Nation pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on pharmacy benefit manager (PBM) payment methodologies, among other things. These actions and policies may significantly reduce U.S. drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks. In June 2024, the U.S. Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations. Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program. Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

The Foreign Corrupt Practices Act

The Foreign Corrupt Practices Act (FCPA), prohibits any U.S. individual or business from paying, offering, or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

Additional Regulation

In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect our business. These and other laws govern our use, handling and disposal of various biological, chemical and radioactive substances used in, and wastes generated by, our operations. If our operations result in contamination of the environment or expose individuals to hazardous substances, we could be liable for damages and governmental fines. We believe that we are in material compliance with applicable environmental laws and that continued compliance therewith will not have a material adverse effect on our business. We cannot predict, however, how changes in these laws may affect our future operations.

Europe / Rest of World Government Regulation

In addition to regulations in the United States, we will be subject to a variety of regulations in other jurisdictions governing, among other things, clinical trials and any commercial sales and distribution of our products. Whether or not we obtain FDA approval of a product, we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or marketing of the product in those countries. Certain countries outside of the United States have a similar process that requires the submission of a clinical trial application much like the IND prior to the commencement of human clinical trials.

For other countries outside of the EU, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country. In all cases, the clinical trials must be conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

If we or our potential collaborators fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension, variation or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Clinical Trials in the EU

Similarly to the United States, the various phases of non-clinical and clinical research in the European Union, or EU are subject to significant regulatory controls. In the EU, clinical trials are governed by the Clinical Trials Regulation (EU) No 536/2014 (CTR), which entered into application on January 31, 2022 repealing and replacing the former Clinical Trials Directive 2001/20 (CTD).

The CTR is intended to harmonize and streamline clinical trial authorizations, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increase transparency. Specifically, the Regulation, which is directly applicable in all EU Member States, introduces a streamlined application procedure through a single-entry point, the “EU portal”, the Clinical Trials Information System (CTIS); a single set of documents to be prepared and submitted for the application; as well as simplified reporting procedures for clinical trial sponsors. A harmonized procedure for the assessment of applications for clinical trials has been introduced and is divided into two parts. Part I assessment is led by the competent authorities of a reference EU Member State selected by the trial sponsor and relates to clinical trial aspects that are considered to be scientifically harmonized across EU Member States. This assessment is then submitted to the competent authorities of all concerned EU Member States in which the trial is to be conducted for their review. Part II is assessed separately by the competent authorities and Ethics Committees in each concerned EU Member State. Individual EU Member States retain the power to authorize the conduct of clinical trials on their territory.

The CTR foresaw a three-year transition period that ended on January 31, 2025. Since this date, all new or ongoing trials are subject to the provisions of the CTR.

In all cases, clinical trials must be conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki. Medicines used in clinical trials, including ATMPs, must be manufactured in accordance with the guidelines on cGMP and in a GMP licensed facility, which can be subject to GMP inspections.

EU Review and approval process of medicinal products

In the EU, medicinal products can only be commercialized after a related marketing authorization (MA) has been granted. To obtain an MA for a product in the EU, an applicant must submit a Marketing Authorization

Application (MAA) either under a centralized procedure administered by the European Medicines Agency (EMA), or one of the procedures administered by the competent authorities of EU Member States (decentralized procedure, national procedure or mutual recognition procedure). An MA may be granted only to an applicant established in the EU.

The centralized procedure provides for the grant of a single MA by the European Commission that is valid throughout the EEA (which is comprised of the 27 EU Member States plus Norway, Iceland and Liechtenstein). Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for (i) medicinal products derived from biotechnological processes, (ii) products designated as orphan medicinal products, (iii) advanced therapy medicinal products, or ATMPs, and (iv) products with a new active substance indicated for the treatment of HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto-immune and other immune dysfunctions and viral diseases. For products with a new active substance indicated for the treatment of other diseases and products that are highly innovative or for which a centralized process is in the interest of patients, authorization through the centralized procedure is optional on related approval.

Under the centralized procedure, the EMA’s Committee for Medicinal Products for Human Use (CHMP) conducts the initial assessment of a product. The CHMP is also responsible for several post-authorization and maintenance activities, such as the assessment of modifications or extensions to an existing MA. The maximum timeframe for the evaluation of an MAA under the centralized procedure is 210 days, excluding clock stops when additional information or written or oral explanation is to be provided by the applicant in response to questions of the CHMP. Accelerated assessment may be granted by the CHMP in exceptional cases, when a medicinal product targeting an unmet medical need is expected to be of major interest from the point of view of public health and, in particular, from the viewpoint of therapeutic innovation. If the CHMP accepts a request for accelerated assessment, the time limit of 210 days will be reduced to 150 days (excluding clock stops). The CHMP can, however, revert to the standard time limit for the centralized procedure if it considers that it is no longer appropriate to conduct an accelerated assessment.

Unlike the centralized authorization procedure, the decentralized MA procedure requires a separate application to, and leads to separate approval by, the competent authorities of each EU Member State in which the product is to be marketed. This application is identical to the application that would be submitted to the EMA for authorization through the centralized procedure. The reference EU Member State prepares a draft assessment and drafts of the related materials within 120 days after receipt of a valid application. The resulting assessment report is submitted to the concerned EU Member States who, within 90 days of receipt, must decide whether to approve the assessment report and related materials. If a concerned EU Member State cannot approve the assessment report and related materials due to concerns relating to a potential serious risk to public health, disputed elements may be referred to the Heads of Medicines Agencies’ Coordination Group for Mutual Recognition and Decentralised Procedures—Human (CMDh) for review. The subsequent decision of the European Commission is binding on all EU Member States.

The mutual recognition procedure allows companies that have a medicinal product already authorized in one EU Member State to apply for this authorization to be recognized by the competent authorities in other EU Member States. Like the decentralized procedure, the mutual recognition procedure is based on the acceptance by the competent authorities of the EU Member States of the MA of a medicinal product by the competent authorities of other EU Member States. The holder of a national MA may submit an application to the competent authority of an EU Member State requesting that this authority recognize the MA delivered by the competent authority of another EU Member State.

An MA has, in principle, an initial validity of five years. The MA may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent authority of the EU Member State in which the original MA was granted. To support the application, the MA holder must provide the EMA or the competent authority with a consolidated version of the Common Technical Document providing up-to-date data concerning the quality, safety and efficacy of the product, including all variations introduced since the MA was granted, at least nine months before the MA ceases to be valid. The European Commission or the competent authorities of the EU Member States may decide on justified grounds relating to pharmacovigilance, to proceed with one further five year renewal period for the MA. Once subsequently definitively renewed, the MA shall be valid for an unlimited period. Any authorization which is not followed by the actual placing of the medicinal product on the EU market (for a centralized MA) or on the market of the authorizing EU Member State within three years after authorization ceases to be valid (the so-called sunset clause).

Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the Priority Medicines (PRIME) scheme, which provides incentives similar to the breakthrough therapy designation in the U.S. PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicinal products that target unmet medical needs. Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the EU or, if there is, the new medicinal product will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones. Benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and potentially accelerated MAA assessment once a dossier has been submitted.

In the EU, a “conditional” MA may be granted in cases where all the required safety and efficacy data are not yet available. The European Commission may grant a conditional MA for a medicinal product if it is demonstrated that all of the following criteria are met: (i) the benefit-risk balance of the medicinal product is positive; (ii) it is likely that the applicant will be able to provide comprehensive data post-authorization; (iii) the medicinal product fulfils an unmet medical need; and (iv) the benefit of the immediate availability to patients of the medicinal product is greater than the risk inherent in the fact that additional data are still required. The conditional MA is subject to conditions to be fulfilled for generating the missing data or ensuring increased safety measures. It is valid for one year and must be renewed annually until all related conditions have been fulfilled. Once any pending studies are provided, the conditional MA can be converted into a traditional MA. However, if the conditions are not fulfilled within the timeframe set by the EMA and approved by the European Commission, the MA will cease to be renewed.

An MA may also be granted “under exceptional circumstances” where the applicant can show that it is unable to provide comprehensive data on efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced. These circumstances may arise in particular when the intended indications are very rare and, in the state of scientific knowledge at that time, it is not possible to provide comprehensive information, or when generating data may be contrary to generally accepted ethical principles. Like a conditional MA, an MA granted in exceptional circumstances is reserved to medicinal products intended to be authorized for treatment of rare diseases or unmet medical needs for which the applicant does not hold a complete data set that is required for the grant of a standard MA. However, unlike the conditional MA, an applicant for authorization in exceptional circumstances is not subsequently required to provide the missing data. Although the MA “under exceptional circumstances” is granted definitively, the risk-benefit balance of the medicinal product is reviewed annually, and the MA will be withdrawn if the risk-benefit ratio is no longer favorable.

Advanced Therapy Medicinal Products in the EU

ATMPs include gene therapy products as well as somatic cell therapy products and tissue engineered products. The grant of marketing authorization in the EU for products containing viable human tissues or cells such as gene therapy medicinal products is governed by Regulation (EC) No. 1394/2007 on ATMPs, read in combination with Directive (EC) No. 2001/83 of the European Parliament and of the Council, commonly known as the Community code on medicinal products. Regulation (EC) No. 1394/2007 establishes specific rules concerning the authorization, supervision and pharmacovigilance of gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineered products. Manufacturers of advanced therapy medicinal products must demonstrate the quality, safety and efficacy of their products to the EMA which is required to provide an opinion regarding the application for marketing authorization. The European Commission grants or refuses marketing authorization in light of the opinion delivered by the EMA.

Products made from substances of human origin must also comply with Regulation (EU) 2024/1938 on standards of quality and safety for substances of human origin intended for human application. This Regulation describes the conditions and quality requirements which must be applied when sourcing the substances of human origin intended for manufacturing of such medicinal products and removed divergences between EU Member States that were present under the (now repealed) Directive (EC) No. 2004/23.

Pediatric Development in the EU

In the EU, Regulation (EC) No 1901/2006 provides that all MAAs for new medicinal products have to include the results of trials conducted in the pediatric population, in compliance with a pediatric investigation plan, or PIP, agreed with the EMA’s Pediatric Committee (PDCO). The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the medicinal product for which MA is being sought. The PDCO can grant a deferral of the obligation to implement some or all of the measures provided in the PIP until there are sufficient data to demonstrate the efficacy and safety of the product in adults. Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when these data are not needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for pediatric patients. Once the MA is obtained in all EU Member States and study results are included in the product information, even when negative, the product is eligible for a six-month extension to the Supplementary Protection Certificate (SPC), if any is in effect at the time of authorization or, in the case of orphan medicinal products, a two-year extension of orphan market exclusivity.

Manufacturing Regulation in the EU

In addition to an MA, various other requirements apply to the manufacturing and placing on the EU market of medicinal products. The manufacturing of medicinal products in the EU requires a manufacturing authorization and import of medicinal products into the EU requires a manufacturing authorization allowing for import. The manufacturing authorization holder must comply with various requirements set out in the applicable EU laws, regulations and guidance, including EU cGMP standards. Similarly, the distribution of medicinal products within the EU is subject to compliance with the applicable EU laws, regulations and guidelines, including the requirement to hold appropriate authorizations for distribution granted by the competent authorities of EU Member States. Marketing authorization holders and/or manufacturing and import authorization, or MA holders and/or distribution authorization holders may be subject to civil, criminal or administrative sanctions, including suspension of manufacturing authorization, in case of non-compliance with the EU or EU Member States’ requirements applicable to the manufacturing of medicinal products.

Data and Market Exclusivity in the EU

The EU provides opportunities for data and market exclusivity related to MAs. Upon receiving an MA, innovative medicinal products are generally entitled to receive eight years of data exclusivity and ten years of market exclusivity. Data exclusivity, if granted, prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic application or biosimilar application for eight years from the date of authorization of the innovative product, after which a generic or biosimilar MAA can be submitted, and the innovator’s data may be referenced. The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU until 10 years have elapsed from the initial MA of the reference product in the EU. The overall ten-year period may, occasionally, be extended for a further year to a maximum of 11 years if, during the first eight years of those ten years, the MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical/biological entity, and products may not qualify for data exclusivity.

In the EU, there is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product. For such products, the results of appropriate preclinical or clinical trials must be provided in support of an application for MA. Guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological product.

Orphan Designation in the EU

In the EU, Regulation (EC) No. 141/2000, as implemented by Regulation (EC) No. 847/2000 provides that a medicinal product can be designated as an orphan medicinal product by the European Commission if its sponsor can establish that: (i) the product is intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions; (ii) either (a) such conditions affect not more than five in 10,000 persons in the EU when the application is made, or (b) the product without the benefits derived from orphan status, would not generate sufficient return in the EU to justify the necessary investment in developing the medicinal product; and (iii) there exists no satisfactory authorized method of diagnosis, prevention, or treatment of the condition that has been authorized in the EU, or even if such method exists, the product will be of significant benefit to those affected by that condition.

Regulation (EC) No 847/2000 sets out further provisions for implementation of the criteria for designation of a medicinal product as an orphan medicinal product. An application for the designation of a medicinal product as an orphan medicinal product must be submitted at any stage of development of the medicinal product but before filing of an MAA. An MA for an orphan medicinal product may only include indications designated as orphan. For non-orphan indications treated with the same active pharmaceutical ingredient, a separate marketing authorization has to be sought.

Orphan medicinal product designation entitles an applicant to incentives such fee reductions or fee waivers, protocol assistance, and access to the centralized marketing authorization procedure. Upon grant of a marketing authorization, orphan medicinal products are entitled to a ten-year period of market exclusivity for the approved therapeutic indication, which means that the EMA cannot accept another marketing authorization application or accept an application to extend for a similar product and the European Commission cannot grant a marketing authorization for the same indication for a period of ten years. The period of market exclusivity is extended by two years for orphan medicinal products that have also complied with an agreed PIP. No extension to any supplementary protection certificate can be granted on the basis of pediatric studies for orphan indications. Orphan medicinal product designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

The period of market exclusivity may, however, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria on the basis of which it received orphan medicinal product destination, including where it can be demonstrated on the basis of available evidence that the original orphan medicinal product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold. Additionally, an MA may be granted to a similar medicinal product with the same orphan indication during the ten year period if: (i) if the applicant consents to a second original orphan medicinal product application, (ii) if the manufacturer of the original orphan medicinal product is unable to supply sufficient quantities; or (iii) if the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior to the original orphan medicinal product. A company may voluntarily remove a product from the register of orphan products.

Post-authorization Requirements in the EU

Where an MA is granted in relation to a medicinal product in the EU, the holder of the MA is required to comply with a range of regulatory requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products. Similar to the United States, both MA holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA, the European Commission and/or the competent regulatory authorities of the individual EU Member States. The holder of an MA must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance who is responsible for oversight of that system. Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports (PSURs).

All new MAAs must include a risk management plan (RMP) describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product. The regulatory authorities may also impose specific obligations as a condition of the MA. Such risk- minimization measures or post-authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization safety studies.

In the EU, the advertising and promotion of medicinal products are subject to both EU and EU Member States’ laws governing promotion of medicinal products, interactions with physicians and other healthcare professionals, misleading and comparative advertising and unfair commercial practices. General requirements for advertising and promotion of medicinal products, such as direct-to-consumer advertising of prescription medicinal products are established in EU law. However, the details are governed by regulations in individual EU Member States and can differ from one country to another. For example, applicable laws require that promotional materials and advertising in relation to medicinal products comply with the product’s Summary of Product Characteristic (SmPC), which may require approval by the competent national authorities in connection with an MA. The SmPC is the document that provides information to physicians concerning the safe and effective use of the product. Promotional activity that does not comply with the SmPC is considered off-label and is prohibited in the EU.

Pricing, Coverage and Reimbursement in the EU

In the EU, pricing and reimbursement schemes vary widely from country to country. Some EU Member States may approve a specific price for a product, or they may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market. Other EU Member States allow companies to fix their own prices for products but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions.

Moreover, in order to obtain reimbursement for our products in some European countries, including some EU Member States, we may be required to compile additional data comparing the cost-effectiveness of our products to other available therapies. This Health Technology Assessment (HTA) of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in some EU Member States, including those representing the larger markets. The HTA process is the procedure to assess therapeutic, economic and societal impact of a given medicinal product in the national healthcare systems of the individual country. The outcome of an HTA will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EU Member States. The extent to which pricing and reimbursement decisions are influenced by the HTA of the specific medicinal product currently varies between EU Member States. In December 2021, Regulation No 2021/2282 on HTA, was adopted in the EU. This Regulation, which entered into application on January 12, 2025 and has a phased implementation, is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EU level for joint clinical assessments in these areas. The Regulation permits EU Member States to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the most potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas. Individual EU Member States continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technologies, and making decisions on pricing and reimbursement.

Corporate Philanthropy

We have joined the Pledge 1% Movement, a global movement that supports the integration of philanthropy into corporate culture by inspiring companies to donate 1% of product, equity, profit, or employee time to causes of their choice, demonstrating our commitment to philanthropic leadership, particularly in the biotechnology sector. As such, in July 2021, our board of directors approved the reservation of up to 84,556 shares of our common stock (which was approximately 1.0% of our fully-diluted capitalization as of that date) that we may issue to or for the benefit of a charitable foundation established by us or other appropriate charitable recipients pursuant to our Pledge 1% Movement commitment. We have not yet issued any such reserved common stock. If any reserved common stock is issued pursuant to our Pledge 1% Movement commitment, we may incur a non-cash expense in the quarter that we issue such shares equal to the fair value of the shares of our common stock issued. Such donation of shares may also dilute our stockholders’ ownership of our common stock. Pursuant to this pledge, we plan to implement programs to encourage our employees to donate 1% of their time to charitable causes.

Facilities

Our principal office is located at 5505 Morehouse Drive, Suite 100, San Diego, California 92121, where we lease 51,621 square feet of space to house our principal office, research and process development laboratories and a cGMP manufacturing center to support our pipeline development and clinical trial supply. This lease will expire in 2029, subject to our option to an additional five-year term. We also had a lease agreement for an additional 13,405 square feet of office space in San Diego, California. We leased this space under a lease that terminated in December 2025. In addition, we have entered into a temporary license agreement for our occupation and use of an additional 11,960 square feet of office and laboratory space in San Diego, California which expires in August 2026. Further, we have a lease agreement for a warehouse and storage facility space in San Diego which has an initial term through August 2029. We believe that these facilities will be adequate for our near-term needs. If required, we believe that suitable additional or alternative space would be available in the future on commercially reasonable terms.

Employees and Human Capital Resources

As of December 31, 2025, we had 104 full-time employees, 21 of whom held an M.D., Pharm.D. or Ph.D. degree and all of whom are engaged in research and development activities, operations, finance and administration. None of our employees are represented by a labor union or covered by a collective bargaining agreement. We consider our relationship with our employees to be good.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

Legal Proceedings

From time to time, we may become involved in litigation or other legal proceedings. We are not currently a party to any litigation or legal proceedings that, in the opinion of our management, are likely to have a material adverse effect on our business. Regardless of outcome, litigation can have an adverse impact on us because of defense and settlement costs, diversion of management resources and other factors.

Corporate Information

We were incorporated under the laws of the State of Delaware on February 14, 2019. Our principal executive offices are located at 5505 Morehouse Drive, Suite 100, San Diego, California, and our telephone number is (858) 267-4467. Our corporate website address is www.artivabio.com. Information contained on, or accessible through, our website shall not be deemed incorporated into and is not a part of this Annual Report on Form 10-K.

All brand names or trademarks appearing in this Annual Report are the property of their respective holders. Use or display by us of other parties’ trademarks, trade dress, or products in this Annual Report is not intended to, and does not, imply a relationship with, or endorsements or sponsorship of, us by the trademark or trade dress owners.

Available Information

Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Sections 13(a) or 15(d) of the Exchange Act are available on our website, free of charge, as soon as reasonably practicable after the reports are electronically filed or furnished to the SEC. The SEC maintains a website at www.sec.gov that contains reports, proxy and information statements, and other information that we file with the SEC electronically. We intend to announce material information to the public through filings with the SEC, the investor relations page on our website, which is located at www.artivabio.com, press releases, public conference calls, and public webcasts.

The information disclosed through the foregoing channels could be deemed to be material information. As such, we encourage investors, the media, and others to follow the channels listed above and to review the information disclosed through such channels. The information we post through these channels is not a part of this Annual Report. Any updates to the list of disclosure channels through which we will announce information will be posted on the investor relations page on our website.