Fate Therapeutics announces expansion of FT516 clinical investigation
Fate Therapeutics announced that the U.S. Food and Drug Administration has allowed its second Investigational New Drug application for FT516, the Company's off-the-shelf natural killer cell product candidate derived from a clonal master induced pluripotent stem cell line engineered to express a novel CD16 Fc receptor. This is the Company's fourth IND from its proprietary iPSC product platform cleared by the FDA, and enables the clinical investigation of FT516 in combination with monoclonal antibody therapy across a broad range of solid tumors. FT516 expresses a novel high-affinity, non-cleavable variant of CD16 that enhances its binding to therapeutic antibodies and prevents its down-regulation, which can significantly inhibit anti-tumor activity. A publication by scientists from the Company, the University of Minnesota, and the University of California, San Diego in the journal Blood, entitled "Pluripotent stem cell-derived NK cells with high-affinity non-cleavable CD16a mediate improved anti-tumor activity," highlights preclinical proof-of-concept data for FT516. In the published studies, iPSC-derived NK cells expressing hnCD16 were shown to have superior therapeutic properties in vitro, including maintenance of CD16 expression and increased levels of cytokine production upon activation, compared to peripheral blood NK cells sourced from healthy donors. In an in vivo systemic tumor model of human lymphoma, treatment with iPSC-derived hnCD16 NK cells plus anti-CD20 mAb resulted in a significant improvement in survival compared to treatment with anti-CD20 mAb alone or in combination with peripheral blood NK cells sourced from healthy donors. Additionally, iPSC-derived hnCD16 NK cells plus anti-HER2 mAb also conveyed a survival benefit in a xenograft model of SKOV-3 ovarian carcinoma. FT516 is the first-ever cell therapy in the world derived from a genetically engineered pluripotent stem cell cleared for clinical testing. The Company intends to initiate clinical investigation of FT516 in combination with tumor-target antibody therapy in solid tumors later this year. The Company is currently conducting an open-label, multi-dose Phase 1 clinical trial of FT516 as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed mAbs for the treatment of advanced B-cell lymphoma.