Fate Therapeutics Announces FDA Clearance of IND Application for FT538, First CRISPR-edited, iPSC-derived Cell Therapy
Phase 1 Clinical Study to Evaluate Multiple Doses of FT538 as Monotherapy for Acute Myeloid Leukemia and in Combination with Anti-CD38 Monoclonal Antibody Therapy for Multiple Myeloma
Off-the-shelf NK Cell Product Candidate Derived from Clonal Master iPSC Line Engineered with Three Functional Components to Enhance Innate Immunity
“We are very pleased to expand the clinical application of our proprietary iPSC product platform to multiple myeloma, where rates of relapse remain high,” said
The three functional components of FT538 are designed to boost the innate immune response 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 endogenous NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action including:
- Expression of the hnCD16 Fc receptor, which improves antibody-dependent cellular cytotoxicity, a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells;
- Expression of the IL-15RF cytokine complex, which promotes NK cell survival and persistence and induces trans-activation of endogenous NK cells and CD8 T cells; and
- Elimination of CD38 expression, which enhances innate effector function, including granzyme and perforin levels and resistance to oxidative stress, and prevents anti-CD38 antibody-mediated NK cell death.
The first-in-human, multi-center, dose-escalation Phase 1 clinical trial of FT538 is designed to determine the maximum tolerated dose (MTD) of three once-weekly doses of FT538 in up to 105 adult patients across four dose cohorts (100M cells per dose; 300M cells per dose; 900M cells per dose; and 1.5B cells per dose). The study will assess two treatment regimens: Regimen A as a monotherapy in patients with relapsed / refractory AML; and Regimen B in combination with daratumumab, an FDA-approved anti-CD38 monoclonal antibody, in patients with relapsed / refractory multiple myeloma who have failed at least two lines of therapy. In addition, the Company may initiate a third treatment regimen in combination with elotuzumab, an FDA-approved anti-SLAMF7 monoclonal antibody, in patients with relapsed / refractory multiple myeloma who have failed at least two lines of therapy starting at one dose level below the MTD of Regimen B. For all regimens, multiple indication- or dose-specific dose-expansion cohorts of up to 15 patients per cohort may be enrolled to further evaluate the clinical activity of FT538.
FT538 is the fourth off-the-shelf, iPSC-derived NK cell product candidate from the Company’s proprietary iPSC product platform cleared for clinical investigation by the FDA. The Company has initiated clinical manufacture of FT538 at its GMP facility in
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 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 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 300 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 FT538, and the Company’s clinical development strategy for 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 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 FT538 may not be replicated in ongoing or future clinical trials or studies, and the risk that FT538 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.