FDA clears Fate Therapeutics’ IND for FT839, an off‑the‑shelf dual‑CAR iPSC‑derived T‑cell therapy targeting CD19 and CD38, enabling a Phase 1/2 basket trial in autoimmune diseases beginning 2H 2026.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration has cleared the Investigational New Drug application for FT839, Fate Therapeutics’ investigational off-the-shelf dual-CAR T-cell therapy targeting CD19 and CD38, enabling the therapy to enter Phase 1/2 clinical development for autoimmune diseases. Patient enrollment is expected to begin in the second half of 2026.
The first-in-human basket trial will evaluate FT839 in combination with standard-of-care therapy across several autoimmune conditions, with treatment administered with or without conditioning chemotherapy. The program expands Fate Therapeutics’ induced pluripotent stem cell (iPSC)-derived CAR T-cell platform beyond B-cell depletion by targeting multiple immune cell populations involved in complex autoimmune disease.
Dual-CAR approach targets multiple disease-driving immune cells
Unlike conventional CD19-directed CAR T-cell therapies, FT839 combines two chimeric antigen receptors to target both CD19-positive B cells and CD38-expressing plasma cells, activated T cells, macrophages, and natural killer (NK) cells. This broader immune cell depletion aims to restore immune balance in autoimmune disorders driven by multiple pathogenic immune cell types.
The therapy is manufactured from a clonal iPSC master cell bank, allowing standardized, off-the-shelf production rather than creating an individualized product for each patient. Fate says this approach may reduce manufacturing complexity, improve availability, and lower production costs compared with autologous CAR T-cell therapies.
FT839 also incorporates 13 targeted genetic edits that support immune evasion, enhanced persistence, multi-antigen targeting, and improved safety. Among these modifications is the company’s Sword & Shield™ technology, which combines an Alloimmune Defense Receptor with CD58 knockout to help the CAR T cells evade host immune rejection and maintain activity without depending on conditioning chemotherapy.
Additional engineering includes a high-affinity CD16 receptor to enhance antibody-dependent cellular cytotoxicity when combined with approved monoclonal antibodies, a CD3 fusion receptor to enable activation with T-cell engagers, CXCR2 and TGFβ signal redirection receptor modifications to improve trafficking and function within inflamed tissues, and CD38 and TRAC knockouts to improve metabolic fitness while reducing graft-versus-host disease risk.
Phase 1/2 basket study will evaluate multiple autoimmune diseases
The Phase 1/2 basket trial will assess the safety, tolerability, and preliminary clinical activity of FT839 across several autoimmune diseases. Initial indications include rheumatoid arthritis, ANCA-associated vasculitis, idiopathic inflammatory myositis, systemic lupus erythematosus with or without lupus nephritis, and systemic sclerosis.
The study also allows evaluation of treatment with or without conditioning chemotherapy, potentially streamlining clinical development by combining dose-escalation and expansion phases within a single protocol.
Preclinical studies presented at the 2026 American Society of Gene and Cell Therapy (ASGCT) and European Alliance of Associations for Rheumatology (EULAR) meetings showed FT839 eliminated B cells, plasma cells, activated T cells, and hematologic cancer cells both as monotherapy and in combination with monoclonal antibodies or T-cell engagers. In allogeneic models, Sword & Shield technology supported prolonged cell persistence without conditioning chemotherapy.
Platform expansion beyond autoimmune disease
President and Chief Executive Officer Bob Valamehr, Ph.D., M.B.A., said FDA clearance expands the company’s off-the-shelf CAR T-cell platform for complex autoimmune disorders, including rheumatoid arthritis. He noted that dual targeting of CD19 and CD38 may enable broader elimination of disease-driving immune cells than CD19-directed therapies alone while maintaining durable activity through multiple genetic modifications.
FT839 is Fate Therapeutics’ second autoimmune CAR T-cell program after FT819, which is advancing toward a potentially registrational Phase 2 study in lupus nephritis. Beyond autoimmune diseases, the company also plans to evaluate FT839 in investigator-initiated studies for type 1 diabetes and multiple sclerosis, while exploring its potential in B-cell lymphomas, leukemias, and multiple myeloma through its dual-CAR mechanism and combination strategy with monoclonal antibodies and T-cell engagers.
Reference
About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.