お知らせ • Jul 09
Fate Therapeutics Receives FDA Clearance Of Investigational New Drug Application For FT839 Product Candidate
Fate Therapeutics, Inc. had its Investigational New Drug (IND) application for FT839 cleared by the U.S. Food and Drug Administration (FDA). FT839 is the Company’s next-generation, off-the-shelf CAR T-cell product candidate uniquely engineered to co-target CD19 and CD38. With IND clearance, the Company plans to advance FT839 into a basket clinical trial intended to evaluate the product candidate across a range of autoimmune diseases when administered in combination with standard-of-care therapy and without dependence on conditioning chemotherapy. Enrollment in the Phase 1/2 study is expected to commence in the second half of 2026. FT839 is a 13-point edited CAR T cell built with a suite of genetic edits and manufactured as a uniform drug product to support clinical safety and durable efficacy in autoimmune and hematological malignancies. FT839 is the Company’s second CAR T-cell product candidate to advance into clinical development for autoimmune disease, joining FT819, an off-the-shelf, CD19-targeted CAR T-cell candidate currently entering Phase 2 development in a potentially registrational trial in lupus nephritis. FT839 is designed to broaden the reach of off-the-shelf CAR T-cell therapy beyond B-cell depletion by simultaneously targeting CD19 and CD38. The elimination of B-lineage cells, including plasma cells, and CD38-expressing activated and proliferating immune cells (e.g. T cells, macrophages and NK cells) is expected to support comprehensive immune rebalancing across a diverse spectrum of autoimmune conditions. FT839 immune cell targeting can be further extended in combination with approved therapeutic monoclonal antibodies or T-cell engagers. Additionally, the Phase 1/2 trial design allows for accelerated development opportunities by avoiding the gap between separate Phase 1 and Phase 2 trials and is intended to enable assessment of both safety and efficacy data in a single trial. FT839 has been engineered with 13 targeted genetic edits that together confer multi-antigen targeting, immune evasion, and enhanced functional persistence, and that are designed to overcome key limitations of autologous patient-derived and allogeneic donor-derived CAR T-cell therapy, including manufacturing complexity, high cost, limited on-demand availability, and the requirement for intensive conditioning chemotherapy. Analogous to master cell banks used to mass produce biopharmaceutical drug products such as monoclonal antibodies, a precisely engineered clonal master iPSC bank serves as the starting cell source to manufacture FT839, overcoming numerous limitations associated with patient- and donor-sourced CAR T-cell therapies. FT839 is well-defined and uniform in composition, produced at a low cost of goods, and can be stored in inventory for off-the-shelf, on-demand availability to enable access for a broad patient population. FT839 multiplexed engineering includes the following functional elements: Dual CD19 and CD38 chimeric antigen receptors (CARs) to eliminate aberrant and pathogenic immune cells such as B cells, plasma cells, macrophages and activated T cells, as well as hematologic cancer cells of lymphoma, leukemia, and myeloma origin. High-affinity, non-cleavable CD16 (hnCD16) Fc receptor to maximize antibody-dependent cellular cytotoxicity (ADCC) in combination with approved therapeutic monoclonal antibodies (for example, rituximab or obinutuzumab), extending coverage against antigen-heterogeneous and antigen-escape populations. CD3e Fusion Receptor (CD3FR) to support T-cell engager (TCE)–driven activation in combination with approved bispecific engagers (for example, epcoritamab, teclistamab or talquetamab). Sword & Shield™ technology (comprising an Alloimmune Defense Receptor and a CD58 genetic knockout) to selectively eliminate and evade host allogeneic immune responses, promote functional persistence, and thereby avoid the need for conditioning chemotherapy. Synthetic chemokine receptor CXCR2 and a TGFß signal redirection receptor (TGFß SRR) to improve trafficking to sites of pathological activity and to counter the immunosuppressive effects of the tissue microenvironment. CD38 and TRAC genetic knockouts to enhance metabolic fitness and safety profile by avoiding the risk of graft versus host disease in allogeneic setting, respectively. In preclinical studies, including data presented at the 2026 American Society of Gene and Cell Therapy (ASGCT) and at the European Congress of Rheumatology (EULAR) Annual Meetings, FT839 selectively eliminated autoimmune disease drivers such as B cells, plasma cells, and activated T cells, as well as hematologic cancer cells, both as monotherapy through its dual CARs and in combination with therapeutic monoclonal antibodies and T-cell engagers. In allogeneic settings, Sword & Shield™ technology supported enhanced persistence and durable activity of FT839 without conditioning chemotherapy. The Phase 1/2 study consists of a multi-indication basket trial designed to evaluate the safety, tolerability, and preliminary activity of FT839 administered in combination with standard-of-care therapy, with or without the use of conditioning chemotherapy, in patients with autoimmune disease. The initial autoimmune indications to be evaluated in the trial are: Rheumatoid arthritis, ANCA-associated vasculitis, Idiopathic inflammatory myositis, Systemic lupus erythematosus with or without nephritis, and Systemic sclerosis. The company also plans to investigate the activity of FT839 in other autoimmune diseases, including Type 1 diabetes and multiple sclerosis, through investigator-initiated trials. Beyond autoimmune disease, the Company believes the dual-CAR mechanism of FT839 and ability to combine with therapeutic monoclonal antibodies and T-cell engagers also support its potential in hematologic malignancies, including B-cell lymphomas, leukemias, and multiple myeloma. FT839 is the Company’s first multi-antigen dual-CAR T-cell product candidate that is designed to express two unique CARs: a first CAR targeting the B-cell lineage marker CD19 and the second CAR targeting the immune activation marker CD38, which is often found on aberrant T, NK and B cells. FT839 is the second product candidate to contain the Company’s Sword and ShieldTM technology. At the 2025 ASH Annual Meeting, the Company presented preclinical data demonstrating the ability of FT839, with its dual-CAR mechanism and unique ability to synergize with monoclonal antibodies and T-cell engagers through its incorporated hnCD16 Fc receptor and CD3 fusion receptor, respectively, to specifically eliminate a variety of pathogenic immune cell types without requiring conditioning chemotherapy, suggesting its potential to broadly treat complex autoimmune diseases and hematologic malignancies.