FT819 Exhibits Enhanced Tumor Clearance In Vivo Compared to Primary CAR T Cells in Preclinical Leukemia Model

Master Engineered iPSC Line for FT819 Fully Characterized for Complete Elimination of TCR Expression and Integration of Novel 1XX CAR into TRAC Locus with No Evidence of Off-target Effects

Company Plans to Submit an IND Application for FT819 during 1H20

SAN DIEGO, Dec. 10, 2019 (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 new in vivo preclinical data for FT819, its first off-the-shelf, iPSC-derived chimeric antigen receptor (CAR) T-cell product candidate, at the 61st American Society of Hematology (ASH) Meeting and Exposition in Orlando, Florida.

FT819 is derived from a clonal master engineered induced pluripotent stem cell (iPSC) line with complete elimination of T-cell receptor (TCR) expression and a novel 1XX CAR targeting CD19 inserted into the T-cell receptor alpha constant (TRAC) locus. The cell product candidate is being developed under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D. The Company has now selected a single engineered iPSC clone, and generated and fully-characterized the master engineered iPSC bank for GMP production of FT819.

CAR T-cell therapy continues to deliver remarkable outcomes for patients with hematologic malignancies, and next-generation approaches are needed to enable broad and timely patient access and reduce the cost and complexity of therapy, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. With early evidence of clinical activity for our off-the-shelf, iPSC-derived NK cell programs, we are excited to lead in bringing next-generation CAR T-cell therapies to patients and plan to submit an IND for FT819 in the first half of 2020.

The Companys iPSC product platform unites stem cell biology and precision genetic engineering to create renewable master engineered iPSC lines that can be repeatedly used to mass produce cancer-fighting immune cells, replacing the high production costs, weeks of manufacturing time, and complex engineering processes required for current-generation CAR T-cell immunotherapies with an off-the-shelf product that has the potential to reach many more patients.

At ASH, scientists from the Company and MSK presented new in vivo preclinical data demonstrating that FT819 exhibits durable tumor control and extended survival. In a stringent xenograft model of disseminated lymphoblastic leukemia, FT819 demonstrated enhanced tumor clearance and control of leukemia as compared to primary CAR19 T cells. At Day 35 following administration, a bone marrow assessment showed that FT819 persisted and continued to demonstrate tumor clearance, whereas primary CAR T cells, while persisting, were not able to control tumor growth. Over the past twelve months, the collaboration team has worked to optimize its processes for making T cells from iPSCs, and has now shown the production of pure T-lymphocytes consisting of both CD8+ and CD4+ T cells having a global gene expression profile that is highly-similar to primary T cells based on a principal component analysis.

As proof-of-principle for the unique advantages arising from selecting a single engineered iPSC clone for the production of CAR T-cell therapy, the scientists assessed 747 clones after engineering a pool of cells using CRISPR. It was found that only about 2% of clones met the Companys standards for overall quality including containing both bi-allelic disruption of the TCR, proper insertion of the CAR into the TRAC locus without random transgene integrations, and no evidence of off-target genomic modifications or translocations. The Company selected the top-performing clone for generation of the master engineered iPSC bank for GMP production of FT819.

Fate Therapeutics has exclusively licensed from MSK foundational intellectual property covering the production and composition of iPSC-derived T cells. In August, the Company announced that the U.S. Patent and Trademark Office issued U.S. Patent No. 10,370,452 covering compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell, including an iPSC. The foundational patent, which expires in 2034, is owned by MSK and is licensed exclusively to Fate Therapeutics for all human therapeutic uses.

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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.

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 cell product candidates, including FT819, its ongoing and planned clinical studies, and the expected clinical development plans for FT819. 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 FT819, may not be replicated in 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 Presents its First Off-the-shelf, iPSC-derived CAR T-Cell Cancer Immunotherapy Program at ASH Annual Meeting - Yahoo Finance