Fate Therapeutics Treats First Lupus Patient in Phase 1 FT819 CAR T-cell Study

Fate Therapeutics, Inc., a clinical-stage biopharmaceutical company, has announced the treatment of the first patient with systemic lupus erythematosus (SLE) in its Phase 1 autoimmunity study of FT819. This off-the-shelf, CD19-targeted chimeric antigen receptor (CAR) T-cell therapy uses induced pluripotent stem cell (iPSC)-derived cells. Additionally, at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting, the company presented data from the Phase 1 study of FT819 in relapsed/refractory B-cell malignancies and initial clinical observations from its FT522 CAR NK cell program in relapsed/refractory B-cell lymphoma (BCL).

The Phase 1 study of FT819 is a multi-center trial aimed at evaluating the safety, pharmacokinetics, and anti-B cell activity in patients with moderate-to-severe SLE. The first patient, a 27-year-old woman with a decade-long history of refractory SLE, received conditioning chemotherapy followed by a single dose of FT819, amounting to 360 million cells. The patient was discharged after a three-day hospital stay without notable adverse events. A pre-treatment blood sample showed that FT819 induced rapid and potent depletion of CD19+ B cells in an ex vivo cytotoxicity assay.

Dr. Jennifer Medlin, the Principal Investigator at the University of Nebraska Medical Center, highlighted the potential of FT819 to provide novel therapeutic solutions with disease-modifying potential for autoimmune diseases. According to her, off-the-shelf cell products like FT819 could overcome critical challenges such as the need for apheresis, extended hospitalization, and significant adverse events.

Scott Wolchko, President, and CEO of Fate Therapeutics, expressed excitement over the potential of their iPSC product platform and its first candidates to treat autoimmune diseases. The platform's preclinical and translational data from both the FT819 CAR T-cell program and the FT522 CAR NK cell program demonstrate key therapeutic mechanisms of activity for autoimmunity. Wolchko emphasized that these programs have a favorable safety profile, convenience, and the ability to offer comprehensive B cell depletion necessary to induce an immune reset in patients with B-cell mediated autoimmune diseases.

FT819 is designed to target CD19 and comprises CD8αβ+ T cells with a memory phenotype and high CXCR4 expression to facilitate tissue trafficking. Data presented at ASGCT from the Phase 1 B-cell malignancies study demonstrated that a single dose of FT819 exhibited multiple therapeutic mechanisms implicated in generating an immune reset. Blood samples from 23 patients treated for relapsed/refractory B-cell lymphoma showed rapid and deep CD19+ B cell depletion, with sustained suppression in the periphery during the initial 30-day period post-administration. Case studies showed secondary and tertiary tissue trafficking, complete elimination of CD19+ cells in tissue, and plasma cell depletion with B-cell reconstitution showing recovery of naïve and immature phenotypes.

FT522, another off-the-shelf, CD19-targeted CAR NK cell product candidate, incorporates a novel alloimmune defense receptor (ADR) designed to increase potency without needing conditioning chemotherapy. Initial clinical observations from the ongoing Phase 1 BCL study showed that the first two patients treated with FT522 experienced rapid, deep, and sustained B-cell depletion in the periphery throughout the treatment cycle, with enhanced persistence compared to previous-generation products.

The company plans to submit an Investigational New Drug (IND) application to the U.S. FDA for FT522 in the middle of 2024, targeting various autoimmune diseases without conditioning chemotherapy.

Fate Therapeutics leverages the unique properties of iPSCs, such as unlimited self-renewal and differentiation potential, to create engineered cell products for off-the-shelf availability. The company's iPSC product platform is supported by an extensive intellectual property portfolio and is designed to address limitations associated with patient- or donor-sourced cells. Based in San Diego, CA, Fate Therapeutics continues its efforts to bring innovative cellular immunotherapies to patients with cancer and autoimmune diseases.