Fate Therapeutics Announces New Preclinical Data for FT596 Off-the-Shelf, iPSC-derived CAR NK Cell Cancer Immunotherapy
FT596 as a Monotherapy Demonstrates Comparable Anti-tumor Activity to CAR19 T Cells In Vivo in Humanized Mouse Model of Lymphoma
Combination of FT596 with Rituximab Shows Durable Tumor Clearance In Vivo in Preclinical Lymphoma Model
Company Plans to Initiate Enrollment of First-in-human Clinical Trial of FT596 in Early 2020
“Current patient- and donor-specific CAR T-cell immunotherapies recognize only one antigen and fail to address the significant risk of relapse due to antigen escape. FT596 is ground-breaking in that it is designed to be available off-the-shelf for timely patient access and to promote deeper and more durable responses by targeting multiple tumor-associated antigens,” said Bob Valamehr, Ph.D., Chief Development Officer of
FT596 is the first cellular immunotherapy engineered with three active anti-tumor components to be cleared for clinical investigation by the
New preclinical data presented at ASH showed that FT596 administered as a monotherapy exhibited durable tumor clearance and extended survival in vivo similar to primary CAR T cells in a humanized mouse model of CD19+ lymphoma. Additionally, when combined with the anti-CD20 monoclonal antibody rituximab, FT596 showed enhanced killing of CD20+ lymphoma cells in vivo as compared to rituximab alone. These data confirm previously presented in vitro findings that demonstrate the unique multi-antigen targeting functionality of FT596, and the product candidate’s potential to effectively overcome CD19 antigen escape.
The Company also announced that, in preparation for Phase 1 initiation, it had recently completed GMP production of FT596. In a single small-scale manufacturing campaign, the Company produced over 300 cryopreserved, infusion-ready doses of FT596 at a cost of approximately
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
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 250 issued patents and 150 pending patent applications.
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 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. The
FT516 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 to express a novel high-affinity 158V, non-cleavable CD16 Fc receptor, which has been modified to prevent its down-regulation and enhance its binding to tumor-targeting antibodies. The product candidate is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma (clinicaltrials.gov ID number NCT04023071). CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG antibodies. Numerous clinical studies with
This 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 Company’s NK cell product candidates, including FT596 and FT516, its ongoing and planned clinical studies, and the expected clinical development plans for FT596 and FT516. 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 Company’s 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 FT596 and FT516, may not be replicated in ongoing or 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 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.