Fate Therapeutics has achieved a significant milestone in autoimmune disease treatment by administering its investigational off-the-shelf CAR-T cell therapy FT819 to the first patient with systemic lupus erythematosus (SLE) in a Phase 1 clinical trial. The treatment represents a novel approach using induced pluripotent stem cell (iPSC)-derived CD19-targeted chimeric antigen receptor T-cells to address B-cell mediated autoimmune diseases.
First Patient Treatment Shows Promise
The inaugural patient, a 27-year-old woman with a decade-long history of refractory SLE, received conditioning chemotherapy followed by a single dose of 360 million FT819 cells. The patient was discharged after a three-day hospital stay without notable adverse events, according to the company's announcement. Pre-treatment blood samples demonstrated that FT819 induced rapid and potent depletion of CD19+ B cells in ex vivo cytotoxicity assays.
Dr. Jennifer Medlin, Principal Investigator at the University of Nebraska Medical Center, emphasized the therapeutic potential of this approach. "Off-the-shelf cell products like FT819 could overcome critical challenges such as the need for apheresis, extended hospitalization, and significant adverse events," she stated, highlighting the disease-modifying potential for autoimmune diseases.
Clinical Data Supports Autoimmune Applications
Data presented at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting from the Phase 1 study in relapsed/refractory B-cell malignancies provided compelling evidence for FT819's therapeutic mechanisms relevant to autoimmune diseases. 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.
The study revealed multiple therapeutic mechanisms critical for generating an immune reset. Case studies demonstrated secondary and tertiary tissue trafficking, complete elimination of CD19+ cells in tissue, and plasma cell depletion. Importantly, B-cell reconstitution showed recovery of naïve and immature phenotypes, suggesting the potential for immune system rebalancing.
iPSC Platform Advantages
FT819 is designed to target CD19 and comprises CD8αβ+ T cells with a memory phenotype and high CXCR4 expression to facilitate tissue trafficking. The iPSC-derived approach offers several advantages over traditional patient-sourced CAR-T therapies, including off-the-shelf availability, standardized manufacturing, and the ability to reach a broader patient population.
Scott Wolchko, President and CEO of Fate Therapeutics, expressed enthusiasm about the platform's potential. "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," he stated.
Expanding Pipeline and Future Plans
The multi-center Phase 1 study aims to evaluate the safety, pharmacokinetics, and anti-B cell activity in patients with moderate-to-severe SLE. The company is also advancing FT522, another off-the-shelf, CD19-targeted CAR NK cell product candidate that incorporates a novel alloimmune defense receptor (ADR) designed to increase potency without requiring conditioning chemotherapy.
Initial clinical observations from the ongoing Phase 1 study of FT522 in B-cell lymphoma showed that the first two patients 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 mid-2024, targeting various autoimmune diseases without conditioning chemotherapy.
Platform Technology and Intellectual Property
Fate Therapeutics leverages the unique properties of iPSCs, including 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 of over 500 issued patents and 500 pending patent applications, designed to address limitations associated with patient- or donor-sourced cells.
