Fate Therapeutics Announces FDA Clearance of IND Application for FT596 Off-the-Shelf, iPSC-derived CAR NK Cell Cancer Immunotherapy
FT596 Product Candidate Derived from Clonal Master iPSC Line Engineered with Three Anti-Tumor Functional Components
Designed to Overcome CD19 Antigen Escape and Improve Durability of Response by Targeting Multiple Tumor-associated Antigens
Off-the-Shelf Availability of FT596 Enables Rapid Time-to-Patient Treatment and Broader Patient Access
“FT596 is a ground-breaking product candidate with the potential to supplant current-generation patient-specific and allogeneic CAR19 T-cell immunotherapies, which recognize only one antigen and fail to address the significant risk of relapse due to antigen escape,” said
While CAR19 T-cell therapies have demonstrated profound initial responses, not all patients respond to therapy and, even for those who initially respond, durability of response remains a significant limitation. Downregulation of target antigen CD19 from the tumor cell surface has been clinically demonstrated to be an important mechanism of resistance.
FT596, which is the first cellular immunotherapy engineered with three active anti-tumor components cleared for clinical investigation by the
FT596 is the third off-the-shelf, iPSC-derived NK cell product candidate from the Company’s proprietary iPSC product platform cleared for clinical investigation by the
FT596 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 with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology, which contains a NKG2D transmembrane domain, a 2B4 co-stimulatory domain and a CD3-zeta signaling domain, that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor that has been modified to augment antibody-dependent cellular cytotoxicity by preventing CD16 down-regulation and enhancing CD16 binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity. In preclinical studies of FT596, the Company has demonstrated that the concurrent activation of the CAR and hnCD16 targeting modalities, in combination with IL-15RF signaling, convey synergistic anti-tumor activity. Increased degranulation and cytokine release were observed upon concurrent receptor activation in lymphoma cancer cells as compared to activation of each receptor alone, indicating that dual-antigen engagement may elicit a deeper and more durable response. Additionally, in a mixed cellular composition cytotoxicity assay comprised of CD19+ and CD19- tumor cells, FT596 combined with rituximab effectively eliminated the heterogeneous population of tumor cells, a result that was not observed with single-antigen targeted CAR19 T cells.
About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (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 for patient treatment. As a result, the Company’s 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 fraught with batch-to-batch and cell-to-cell variability that can affect 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.
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the advancement of and plans related to the Company's product candidates and clinical studies, the Company’s progress, plans and timelines for the clinical investigation of its product candidates, the therapeutic potential of the Company’s product candidates including FT596, and the Company’s clinical development strategy for FT596, FT516, and FT500. 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 of difficulties or delay in the initiation of any planned clinical studies, or in the enrollment or evaluation of subjects in any ongoing or future clinical studies, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, difficulties in manufacturing or supplying the Company’s product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), the risk that results observed in preclinical studies of FT596 may not be replicated in ongoing or future clinical trials or studies, and the risk that FT596 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 Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the
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Source: Fate Therapeutics, Inc.