Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, presented initial clinical and translational data from the first patient treated in its FT819 Phase 1 Autoimmunity study for moderate-to-severe systemic lupus erythematosus (SLE) at the American College of Rheumatology (ACR) Convergence being held in Washington, D.C. The patient, a 27-year-old African American-Asian woman diagnosed with lupus nephritis (LN) over ten years ago, received fludarabine-free conditioning followed by a single dose of FT819. The patient achieved DORIS (definition of remission in SLE) clinical remission and LLDAS (low lupus disease activity state) as of Month 6 follow-up. The patient continues on-study, in clinical remission, and free of all immunosuppressive therapies as of a data cutoff date of November 11, 2024. FT819 is the Company’s off-the-shelf, CD19-targeted, 1XX CAR T-cell product candidate comprised of CD8αβ+ T cells with a memory phenotype and high CXCR4 expression to promote tissue trafficking.

“These initial results are incredibly promising. Our patient not only went into drug-free clinical remission but also had resolution of fatigue, something that we as rheumatologists struggle to improve with our treatments,” said Jennifer Medlin, M.D., and Principal Investigator at the University of Nebraska Medical Center. “If we continue to see similar results in other patients with an acceptable safety profile, off-the-shelf CAR T-cell therapy could be a complete game-changer for our sickest lupus patients. This gives me hope for a future where we can make a great impact on these patients with devastating disease.”

Patient 1 Case Study

The patient presented with active LN and severe disease, which was marked by renal BILAG A (British Isles Lupus Assessment Group) disease activity score based on biopsy, SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) score of 20, FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) score of 33 (range 0-52, where a score of 52 indicates no fatigue) and PGA (Physician Global Assessment) score of 2.5 (where a score of 3 indicates most severe activity). Following administration of fludarabine-free conditioning and treatment with a single dose of FT819 at 360 million cells, the patient was discharged from the hospital without notable adverse events (AEs) after a protocol-required three-day stay. As of the data cutoff date, the patient has experienced no Grade ≥3 AEs, no serious adverse events (SAEs), and no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD). The patient reported that her debilitating fatigue had entirely resolved without further treatment, and treatment with methylprednisolone was discontinued at Month 3. The patient achieved DORIS clinical remission, including with resolution of arthritis and active urinary sediment and with a substantial reduction in proteinuria, as of Month 6 follow-up. As of the data cutoff date, the patient continues in DORIS clinical remission and remains free of all immunosuppressive therapy.

Rapid elimination of CD19+ B cells in the periphery was observed following fludarabine-free conditioning and treatment with a single dose of FT819. B-cell recovery by Month 3 was predominantly comprised of naïve, non-class switched B cells with near-complete elimination of switched memory B cells and deep depletion of plasmablasts, indicative of an immune reset. Notably, the unique double-negative (DN) B-cell subset, previously described and associated with severe SLE, was nearly eliminated.

“These seminal data with fludarabine-free conditioning and off-the-shelf CAR T-cell therapy in autoimmunity are exciting, and we are very pleased that the first patient with active lupus nephritis had a favorable clinical experience, achieved drug-free clinical remission, and continues on-study free of all immunosuppressive therapy,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “We believe our highly-differentiated therapeutic approach has the potential to transform outcomes for patients with autoimmune diseases without requiring patient apheresis, discontinuation of maintenance therapy, intense conditioning chemotherapy, and extended hospitalization.”