On December 4, 2018 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported new preclinical data on the Company’s induced pluripotent stem cell (iPSC) product platform and its iPSC-derived, off-the-shelf cell-based cancer immunotherapy pipeline at the 60thAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Fate Therapeutics, DEC 4, 2018, View Source [SID1234531876]). Last week, the Company announced that the U.S. Food and Drug Administration (FDA) allowed its Investigational New Drug (IND) Application for FT500, the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master iPSC line. The clinical trial of FT500 is expected to be the first-ever clinical investigation in the U.S. of an iPSC-derived cell product.
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"Fate Therapeutics is at the forefront in developing off-the-shelf, cell-based cancer immunotherapies, and is rapidly progressing multiple iPSC-derived CAR T- and NK cell product candidates that have the potential to disrupt autologous and allogeneic approaches to cell therapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "The clearance of our FT500 IND by the FDA is a landmark achievement and serves as a roadmap for advancement of our iPSC-derived cell product pipeline into clinical development. We believe the use of clonal master iPSC lines uniquely enables the production of multi-functional, cell-based cancer immunotherapies that are uniformly engineered, are available for off-the-shelf administration to patients and can be effectively combined in multi-dose, multi-cycle regimens with well-established immune-oncology agents, such as checkpoint inhibitor blockade and monoclonal antibody therapy, including in earlier lines of therapy."
Several of the Company’s iPSC-derived cell product candidates undergoing development were discussed during an investor event at ASH (Free ASH Whitepaper) by its collaborating experts in the field of cell-based cancer immunotherapy including:
Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering & Gene Transfer and Gene Expression Laboratory, Memorial Sloan Kettering Cancer Center;
Jeffrey S. Miller, M.D., Deputy Director, Masonic Cancer Center, University of Minnesota; and
Dan S. Kaufman, M.D., Ph.D., Professor of Medicine, Division of Regenerative Medicine, Director of Cell Therapy, University of California – San Diego.
FT500
The clinical trial of FT500 is intended to evaluate the safety and tolerability of multiple doses of FT500, in multiple dosing cycles with nivolumab, pembrolizumab or atezolizumab, in subjects that have progressed or failed on immune checkpoint blockade (CPB) therapy. Although CPB therapy can lead to prolonged responses, refractory disease and progression after initial response remain major causes of mortality. In patients receiving CPB therapy, mutations in beta-2-microglobulin (B2M), an essential component for the stable presentation of antigens by tumor cells, have been identified in approximately 30% of patients with progressing disease and are associated with poor overall survival. Investigators have demonstrated in various tumor model systems that NK cells have the potential to rescue CPB therapy by recognizing and killing B2M-deficient target cells. An oral presentation at ASH (Free ASH Whitepaper) by Dr. Miller showed that FT500 synergizes with T cells and anti-PD1 antibody to produce pro-inflammatory cytokines and completely clear target cancer cells in an in vitro three-dimensional tumor spheroid model.
FT516
FT516 is a universal, off-the-shelf NK cell product candidate manufactured from a clonal master iPSC line engineered to uniformly express a high-affinity, non-cleavable CD16 (hnCD16) Fc receptor. Since CD16 binds the Fc region of tumor-bound antibodies, FT516 can be combined with FDA-approved monoclonal antibody therapies to target a broad spectrum of tumor-associated antigens. In preclinical studies, FT516 exhibits potent and persistent anti-tumor activity in vitro and in vivo against multiple tumor types, including in combination with monoclonal antibody therapies that target CD20, HER2 and EGFR. The Company plans to submit an IND to the FDA by the end of 2018 to evaluate the safety and tolerability of multiple doses of FT516 in multiple dosing cycles in combination with FDA-approved monoclonal antibody therapy.
FT596
FT596 is a universal, off-the-shelf chimeric antigen receptor (CAR) NK cell product candidate that expresses a proprietary CAR targeting CD19, a novel IL-15 receptor fusion for cytokine-independent persistence, and a hnCD16 Fc receptor for augmented antibody-dependent cellular-cytotoxicity (ADCC). A poster presentation at ASH (Free ASH Whitepaper) by scientists from the Company and the University of California – San Diego highlighted new in vivo data demonstrating that FT596 displays long-term persistence without systemic cytokine support. Additionally, FT596 prevents tumor progression and promotes sustained long-term survival in a B-cell leukemia xenograft model. Moreover, as proof-of-concept for the mitigation of antigen escape, FT596 in combination with rituximab completely eliminates CD19+ and CD19- B-cell tumor cells in a co-culture cytotoxicity assay.
FT538
FT538 is a universal, off-the-shelf NK cell product candidate that expresses both a novel IL-15 receptor fusion for cytokine-independent persistence and a hnCD16 Fc receptor for augmented ADCC, and additionally lacks CD38 expression to eliminate fratricide when combined with CD38-targeting monoclonal antibody therapy. A poster presentation at ASH (Free ASH Whitepaper) by scientists from the Company and the University of Minnesota highlighted new in vitro data showing that FT538 in combination with daratumumab is resistant to fratricide and eliminates multiple myeloma cancer cells in a serial re-challenge assay. The Company is investigating the additional therapeutic benefit of including a novel humanized CAR targeting B-cell Maturation Antigen (BCMA) as a dual-targeting mechanism to address multiple myeloma and other BCMA-positive malignancies.
FT819
FT819 is an off-the-shelf, TCR-less CD19 CAR T-cell product candidate manufactured from a clonal master iPSC line that is undergoing preclinical development under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Dr. Sadelain. FT819 is engineered to completely eliminate expression of the T-cell receptor and to insert a next-generation CAR receptor into the T-cell receptor alpha locus, a strategy which is intended to convey enhanced safety and efficacy while eliminating the possibility of graft-versus-host disease. A poster presentation at ASH (Free ASH Whitepaper) by scientists from the Company and MSK showcased new in vivo data demonstrating that FT819, when thawed and directly infused, effectively controls tumor progression comparable to peripheral blood CAR T cells in a preclinical mouse model of acute lymphoblastic leukemia.
A copy of the Company’s presentation from its ASH (Free ASH Whitepaper) investor event can be accessed under "Events & Presentations" in the Investors & Media section of the Company’s website at www.fatetherapeutics.com.
About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary iPSC product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses to mediate 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 Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event, and selecting a single 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 to treat many patients. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 100 issued patents and 100 pending patent applications.