On January 13, 2020 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that the U.S. Food and Drug Administration (FDA) has allowed its second Investigational New Drug (IND) application for FT516, the Company’s off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel CD16 Fc receptor (Press release, Fate Therapeutics, JAN 13, 2020, View Source [SID1234553072]). 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 (mAb) therapy across a broad range of solid tumors.
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"While monoclonal antibodies are proven therapeutic agents that are often used early in the treatment of many cancers, the functional status of the patient’s NK cells has been shown to play an important role in mediating clinical activity and prolonging survival," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "In particular, stable expression of the NK cell activating receptor CD16, and its binding affinity to therapeutic antibodies, are critical to promoting antibody-dependent cellular cytotoxicity. Our first-of-kind, off-the-shelf approach with FT516 enables administration of multiple doses of CD16-engineered NK cells, and we are excited to investigate the potential of FT516 to augment the clinical efficacy of monoclonal antibody therapy in the setting of solid tumors."
FT516 expresses a novel high-affinity, non-cleavable variant of CD16 (hnCD16) 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 (View Source), 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 (median survival exceeding 100 days) compared to treatment with anti-CD20 mAb alone or in combination with peripheral blood NK cells sourced from healthy donors (each of which showed median survival of 35 days). 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.