Fate Therapeutics Announces Publication of FT538 Preclinical Data Demonstrating Enhanced Serial Killing and Functional Persistence without Cytokine Support
“The NK cell community has long sought to improve NK cell activation, cytotoxicity, functional persistence, and tumor targeting for cancer immunotherapy. Our preclinical data demonstrate that the synthetic features of FT538 uniquely harness all these therapeutic attributes and significantly improve NK cell anti-tumor activity,” said Bob Valamehr, Ph.D., Chief Research and Development Officer of
The studies in the Cell Stem Cell publication were conducted as part of a collaboration between scientists at
The peer-reviewed paper describes preclinical studies showing that FT538 shares metabolic, transcriptional, and functional features with adaptive NK cells. The data demonstrate that FT538 persists in vivo at high levels for more than six weeks in the absence of cytokine support after adoptive transfer, whereas adoptively-transferred peripheral blood NK cells required the co-infusion of either IL-2 or IL-15 to achieve low-level persistence for up to two weeks. Additionally, in sequential killing assays, FT538 was shown to have robust serial killing and functional persistence, which were not observed with peripheral blood NK cells. FT538 also incorporates a novel high-affinity, non-cleavable CD16 Fc receptor as a third functional component, which was shown to mediate potent in vivo anti-tumor activity in combination with the CD38-targeted monoclonal antibody daratumumab against MM.1S myeloma cells.
FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia and in combination with daratumumab for the treatment of multiple myeloma (NCT04614636). In addition, the Company has initiated patient enrollment in a multi-dose Phase 1 clinical trial of FT538 in combination with certain monoclonal antibodies targeting EGFR, HER2, and PDL1 for the treatment of solid tumors.
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 with multiple doses to deliver more effective pharmacologic activity, including in combination with 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 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 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 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 350 issued patents and 150 pending patent applications.
FT538 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 functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636).
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the Company’s clinical studies and preclinical research and development programs, its ongoing and planned clinical studies, including its clinical investigation of FT538, and the safety and therapeutic potential of the Company’s product candidates, including FT538. 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’s product candidates may not demonstrate the requisite safety or efficacy to achieve regulatory approval or to warrant further development, the risk that results observed in prior studies of the Company’s product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Company’s product candidates or in the initiation of, or enrollment of patients in, any 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, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in patient enrollment and continuation in the Company’s ongoing and planned clinical trials, 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), 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 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.