NK Cell Therapies

AlloNK® + Rituximab in Refractory RA, Sjogren’s Disease, Myositis, and Systemic Sclerosis

Rheumatoid arthritis (RA) is a systemic, autoimmune disease characterized by symmetrical inflammatory polyarthritis. Additionally, extra-articular features are common and are often associated with poor prognosis. RA affects an estimated 1.5 million patients in the U.S. While most patients are adequately managed using methotrexate and other first-line disease-modifying anti-rheumatic drugs e.g., sulfasalazine, hydroxychloroquine and leflunomide, a proportion of patients require a biologic disease-modifying anti-rheumatic drugs such as adalimumab, infliximab, etanercept, abatacept, tocilizumab, or rituximab and / or a targeted synthetic disease-modifying anti-rheumatic drugs such as baricitinib or tofacitinib), with a further subgroup failing multiple agents.

Sjögren’s disease (SjD) is a chronic autoimmune disease characterized primarily by dry eyes and dry mouth due to the immune system’s attack on the exocrine glands. SjD affects an estimated 260,000 patients in the U.S. While many patients may have mild symptoms, SjD can progress to more advanced disease, with systemic involvement and more severe manifestations. Management of advanced SjD involves a multidisciplinary approach to address both local and systemic manifestations effectively. Although the understanding of the pathogenic mechanisms underlying Sjögren’s disease has progressed, current treatment options focus on managing symptoms. Currently, no single medication has been conclusively proven to slow the progression of SjD nor treat all aspects of the disease. After successful treatment in other autoimmune diseases, a number of biological treatments targeting pathways which mediate B-cell hyperactivity, T-cell co-stimulation and abnormal pro- inflammatory cytokine release are currently being investigated, but none are currently approved for use in Sjögren’s disease.

Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune conditions characterized by inflammation of muscle (myositis) and other organ systems, resulting in widespread organ dysfunction, increased morbidity and early mortality. IIMs affect an estimated 45,000 patients in the U.S.  The most common IIMs are dermatomyositis (DM) with characteristic skin rashes of Gottron papules and heliotrope rash, polymyositis (PM) with an immune attack on myofibers, and inclusion body myositis (IBM). First-line therapy for IIMs consists of high doses of glucocorticoids followed by a taper to the lowest possible dose of glucocorticoids to keep the disease controlled. Additional treatment based on immunosuppressive agents, especially azathioprine, methotrexate, mycophenolate mofetil and cyclosporine, is often required. Therefore, new treatment modalities for IIMs need to be developed to address subjects who are unresponsive to the current standard of care.

Systemic sclerosis (SSc), also known as scleroderma, is a rare connective tissue disorder with complex pathogenesis. Systemic sclerosis can be classified as limited systemic sclerosis or diffuse systemic sclerosis based on clinical and serological criteria. SSc affects an estimated 85,000 patients in the U.S, and is associated with high mortality, having the highest case-specific mortality among all collagen vascular disorders. Treatment of systemic sclerosis is focused on treating the organs affected by the disorder while preventing further damage, but there is currently no treatment that can alter the natural course of the disease, and thus new therapeutic modalities are needed to address this unmet need.

In May 2025 we announced the FDA IND clearance of an open-label Phase 2a study to evaluate the safety and efficacy of AlloNK® in combination with rituximab in refractory RA, SjD, IIMs, and SSc. To our knowledge this represents the first company-sponsored trial to explore an allogeneic cell therapy in rheumatoid arthritis or Sjögren’s disease in the U.S.

AlloNK® + Anti-CD20 Monoclonal Antibodies in Lupus Nephritis

Systemic lupus erythematosus (SLE) is a chronic, potentially severe, autoimmune disease characterized by abnormal B-cell function and autoantibody production resulting in a range of clinical manifestations including end organ damage and an increased risk of death. SLE affects an estimated 200,000 patients in the U.S. Lupus nephritis (LN) is a manifestation of SLE reported to affect approximately half of all patients with SLE. LN occurs when autoantibodies affect parts of the kidneys that filter out waste, which can result in swelling, weight gain from fluid retention, elevated blood pressure and urine that appears foamy from excessive protein loss. Despite the availability of potent therapies, approximately 30% do not respond to currently available treatments, and up to 10% of LN patients still progress to end-stage renal disease, requiring dialysis and eventually, a kidney transplant.

In April 2024, we began dosing patients in our Phase 1/1b open-label, multi-center clinical trial of AlloNK in combination with rituximab or obinutuzumab in patients with class III or class IV LN who previously failed treatment (ClinicalTrials.gov Identifier: NCT06265220). In July 2024 the inclusion criteria were expanded to include patients with SLE, with or without lupus nephritis. 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.

AlloNK® + Rituximab in Investigator-Initiated Basket Trial

In April 2024, the FDA cleared an IND submitted by IRIS, a large community practice rheumatology clinic in Florida, to conduct a basket ITT to assess the safety, tolerability, and clinical activity of AlloNK in combination with rituximab. The IIT will initially enroll patients with rheumatoid arthritis (RA), pemphigus vulgaris (PV), systemic lupus erythematosus (SLE), and the anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) subtypes granultomatosis with polyangiitis (GPA) / microscopic polyangiitis (MPA).

AlloNK® + Anti-CD20 Monoclonal Antibodies in Non-Hodgkin Lymphoma

Our ongoing Phase 1/2 clinical trial (ClinicalTrials.gov Identifier: NCT04673617) is assessing the safety and clinical activity of AlloNK® alone and in combination with the anti-CD20 monoclonal antibody, rituximab. The study is enrolling patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) who have progressed beyond two or more prior lines of therapy. We have observed deep B-cell depletion in the periphery and complete responses in heavily pre-treated patients. We believe these preliminary results 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.

AlloNK® + Acimtamig in CD30-Positive Lymphomas

Artiva and Affimed have entered into a strategic collaboration to jointly develop, manufacture, and commercialize a combination therapy comprised of Artiva’s AlloNK®, and Affimed’s Innate Cell Engager (ICE®) acimtamig (previously known as AFM13) for the treatment of patients with relapsed/refractory CD30-positive lymphomas. The LuminICE-203 study (ClinicalTrials.gov Identifier: NCT05883449) is currently enrolling patients with relapsed or refractory classical Hodgkin lymphoma, and Affimed presented initial data from the first seven patients in June 2024.

AB-201: HER2 CAR-NK

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-positive 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.

AB-205: CD5-Directed CAR-NK

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-positive T-cell leukemia cell lines, CCRF-CEM and RPMI-8402, with AB-205 in vitro and meaningful anti-tumor activity in vivo.

Publications and Presentations

AB-101, an Allogeneic, Non-Genetically Modified, Natural Killer (NK) Cell Therapy, Evaluated as Monotherapy or in Combination with Rituximab in R/R Non-Hodgkin Lymphoma. Presented at: American Society of Clinical Oncology (ASCO) 2023.

AFM13 enhances the anti-tumor activity of AB-101 towards CD30⁺ tumors, conferring tumor growth control in vivo. Presented at: International Conference of Malignant Lymphoma (ICML) 2023.

Combinatorial Immunotherapy of Tetravalent Bispecific AFM13 and AB-101 NK Cell Product Confers Tumor Growth Control In Vivo. Presented at: Society for Natural Immunity (NK2023).

Evaluation of AB-101, an Allogeneic Cord Blood-derived Natural Killer (NK) Cell Therapy, as an ADCC Enhancer in Hematologic and Solid Tumors. Presented at: Society for Immunotherapy of Cancer (SITC) 2022.

Pre-Clinical Efficacy of AB-101, An Allogeneic Cord-Blood Derived Natural Killer (NK) Cell Therapeutic Candidate, in Combination with Anti-CD38 Antibodies in Models of Multiple Myeloma. Presented at: American Society of Hematology (ASH) 2022.

Development of AB-201, a novel allogeneic anti-HER2-specific CAR-NK cell therapy for the treatment of HER2⁺ tumors. Presented at: Society for Immunotherapy of Cancer (SITC) 2021.

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