Fate Therapeutics presents new data from FT819 study

Fate Therapeutics (FATE) presented new clinical and translational data from the company’s FT819 Phase 1 Autoimmunity study for moderate-to-severe systemic lupus erythematosus, or SLE, at the American Society of Hematology, or ASH, annual meeting being held in San Diego. The first three study patients, each of whom presented with active lupus nephritis, or LN, despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning followed by a single dose of FT819 at 360 million cells. There were no dose-limiting toxicities, no events of any grade of cytokine release syndrome, immune effector-cell associated neurotoxicity syndrome, or graft-versus-host disease and rapid, deep, and sustained elimination of CD19+ B cells in the periphery was observed during the first month of treatment. FT819 is the company’s off-the-shelf, CD19-targeted, 1XX CAR T-cell product candidate comprised of CD8ass+ T cells with a memory phenotype and high CXCR4 expression to promote tissue trafficking. The ongoing multi-center, Phase 1 clinical trial for patients with moderate-to-severe SLE is designed to evaluate the safety, pharmacokinetics, and anti-B cell activity of FT819. The first three patients, all of whom presented with active LN despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning consisting of either cyclophosphamide alone or bendamustine alone, followed by a single dose of FT819 at 360M cells. In all three patients, FT819 was detected in the peripheral blood and rapid, deep, and sustained elimination of CD19+ B cells in the periphery was observed during the first month of treatment. All three patients remain on-study, and there have been no DLTs and no events of any grade of CRS, ICANS, or GvHD. Based on these clinical observations, the company is initiating dose expansion in up to 10 patients at this first dose level, and is also escalating dose to 720M cells. The company’s FT819 Phase 1 Autoimmunity study also includes a second treatment arm to assess the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 as an add-on to maintenance therapy without conditioning chemotherapy in patients with SLE. The first patient has now been treated in this second arm, which is being conducted in parallel with the study’s conditioning arm. The first patient treated in the Phase 1 Autoimmunity study presented with active LN and severe disease, which was marked by renal BILAG A disease activity score based on biopsy, SLEDAI-2K score of 20, FACIT-Fatigue score of 33 and PGA score of 2.5. 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, or AEs, after a protocol-required three-day stay. Rapid elimination of CD19+ B cells in the periphery was observed following treatment, and B-cell recovery by Month 3 was predominantly comprised of naive, non-class switched B cells with near-complete elimination of switched memory B cells and deep depletion of plasmablasts, indicative of an immune reset. 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. The patient continues on-study, in DORIS clinical remission, and remains free of all immunosuppressive therapy. The company also highlighted the scientific progress of its proprietary iPSC-derived CAR T-cell product platform at the ASH Annual Meeting. In an oral presentation entitled “Off-the-shelf Product Candidate Incorporates Novel Sword & Shield Technology Designed to Promote Functional Persistence without Conditioning Chemotherapy”, the Company compared its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR alongside the complete knock-out of CD58 to both target and evade host alloreactive immune cells, to other host immune evasion strategies. In preclinical studies of allogeneic models, the Company showed that its Sword and Shield Technology specifically engaged with alloreactive T cells and supported functional persistence while avoiding the killing of general host T cells and activated anti-tumor T cells. This unique observation was not seen with other approaches that are either too broad and undesirably eliminate most of the host immune system or have limited coverage and cannot adequately protect the allogeneic cell product. In a second presentation entitled “Development of Induced Pluripotent Stem Cell-Derived T Cells Exhibiting Phenotypic and Functional Attributes of Primary CAR T Cells”, the company conducted a series of high-resolution analyses to show stimulated iPSC-derived T cells elicit primary T-cell like activation, proliferation, transcriptional and functional program engagement, and iPSC-derived CAR T cells uniquely emulate antigen-mediated response similar to primary-derived autologous CAR T cells.