Fate Therapeutics Announces FDA Clearance of IND Application for World’s First Cell Therapy Derived from an Engineered Pluripotent Stem Cell

Fate Therapeutics announced that the U.S. Food and Drug Administration (FDA) has allowed its 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. FT516 is the first-ever cell therapy derived from a genetically engineered pluripotent stem cell cleared for clinical testing in the world, and is the Company’s second off-the-shelf, iPSC-derived NK cell product candidate cleared for clinical investigation by the FDA within the past two months. The Company intends to initiate clinical testing of FT516 in patients with certain relapsed/refractory hematologic malignancies, including acute myelogenous leukemia (AML) as a monotherapy, non-Hodgkin’s lymphoma (NHL) in combination with rituximab, and multiple myeloma (MM) in combination with elotuzumab.

“This allowance by the FDA of our FT516 IND application is a watershed event in the clinical development of engineered cell therapies. Our industry-leading iPSC product platform enables the manufacture of engineered cell products that can be extensively characterized, cryopreserved and delivered ‘on demand’ to reach more patients,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “FT516 is a first-of-kind cell product in that it originates from a single genetically engineered pluripotent stem cell, which serves as a clonal master cell line that can be repeatedly used to mass-produce large quantities of homogeneous cell product in a cost-effective manner. This innovative approach uniquely supports a new treatment paradigm with engineered cell therapies, where multiple doses of cell product are readily available for administration with the goal of driving deeper and more durable responses. We look forward to treating patients with multiple doses of FT516, including in combination with FDA-approved monoclonal antibody therapy, across multiple treatment cycles in this first clinical study.”

CD16 is naturally expressed on NK cells and mediates antibody-dependent cellular cytotoxicity (ADCC), a potent immune mechanism through which NK cells can recognize, bind and kill antibody-coated cancer cells. ADCC is an underlying mechanism associated with the clinical efficacy of many monoclonal antibodies that are approved for the treatment of various cancers, including hematologic malignancies and solid tumors. The expression of CD16 on NK cells can undergo considerable down-regulation in cancer patients, which significantly inhibits the immune system’s anti-tumor response. FT516 incorporates a novel CD16 Fc receptor, which has been modified to prevent its down-regulation and to augment its binding to tumor-targeting antibodies, for enhanced ADCC.

The initial clinical study of FT516 is intended to assess the safety and tolerability of three weekly doses for the treatment of certain relapsed/refractory hematologic malignancies. The study includes three independent, dose-escalating treatment arms: monotherapy for AML; combination with rituximab for NHL; and combination with elotuzumab, plus pomalidomide and dexamethasone, for MM. All subjects will receive low-dose conditioning chemotherapy consisting of cyclophosphamide and fludarabine (Cy/Flu) and cytokine support with IL-2. Subjects are eligible to receive a second treatment cycle following an initial 28-day safety assessment.

FT516 is the second off-the-shelf, iPSC-derived NK cell product candidate cleared for clinical investigation by the FDA from the Company’s proprietary iPSC product platform. In November 2018, the FDA cleared the Company’s IND application for FT500, an off-the-shelf, iPSC-derived NK cell product candidate for use in combination with checkpoint blockade therapy for the treatment of solid tumors.