FT516 IND Application Cleared by FDA for Advanced Solid Tumors in Combination with PDL1-, EGFR- and HER2-targeting Therapeutic Antibodies

Published Preclinical Data Demonstrate iPSC-derived NK Cells Engineered with High-affinity, Non-cleavable CD16 Enhance the Efficacy of Antibody Therapy

SAN DIEGO, Jan. 13, 2020 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, announced today that the U.S. Food and Drug Administration (FDA) has allowed its second Investigational New Drug (IND) application for FT516, the Companys 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. This is the Companys 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.

While monoclonal antibodies are proven therapeutic agents that are often used early in the treatment of many cancers, the functional status of the patients 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 (https://doi.org/10.1182/blood.2019000621), 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.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 250 issued patents and 150 pending patent applications.

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About FT516FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. The product candidate is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology product candidates include natural killer (NK) cell and T-cell cancer immunotherapies, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens with chimeric antigen receptors (CARs). The Companys immuno-regulatory product candidates include ProTmune, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease, and a myeloid-derived suppressor cell immunotherapy for promoting immune tolerance in patients with immune disorders. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking StatementsThis release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the safety and therapeutic potential of the Companys NK cell product candidates, including FT516, its ongoing and planned clinical studies, and the expected clinical development plans for FT516. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Company may cease or delay planned development and clinical trials of any of its product candidates for a variety of reasons (including any delay in enrolling patients in current and planned clinical trials, requirements that may be imposed by regulatory authorities on the conduct of clinical trials or to support regulatory approval, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, or the occurrence of any adverse events or other negative results that may be observed during development), the risk that results observed in preclinical studies of its product candidates, including FT516, may not be replicated in ongoing or future clinical trials or studies, and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

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Fate Therapeutics Announces Expansion of FT516 Clinical Investigation and Publication of Preclinical Data in the Journal Blood - Yahoo Finance