12/07/2019 | Press release | Distributed by Public on 12/07/2019 09:06
No Morphologic Evidence of Leukemia and Complete Neutrophil Recovery Observed in First Patient Treated with FT516 Monotherapy for AML following First Dosing Cycle
No Dose-limiting Toxicities or FT500-related SAEs Reported in First 12 Patients Treated with FT500 for Advanced Solid Tumors
Favorable FT500 Phase 1 Safety, Tolerability and Immunogenicity Profile Validates Novel Multi-dose Treatment Paradigm for Off-the-shelf, iPSC-derived NK Cell Products
SAN DIEGO, Dec. 07, 2019 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, announced initial clinical data for its FT516 and FT500 off-the-shelf, iPSC-derived natural killer (NK) cell product candidates.
'The safety, tolerability, and immunogenicity data from the Phase 1 dose-escalation stage of FT500, the first-ever cell therapy derived from a clonal master induced pluripotent stem cell line to undergo clinical investigation in the U.S., provide compelling evidence that multiple doses of iPSC-derived NK cells can be delivered off-the-shelf and administered without patient matching,' said Wayne Chu, M.D., Vice President of Clinical Development of Fate Therapeutics. 'Additionally, initial clinical observations with FT516 are very encouraging, as an assessment of the first AML patient's bone marrow at Day 42 following three once-weekly doses of FT516 demonstrated anti-leukemia activity and hematopoietic recovery.'
FT516 Universal, Off-the-shelf, Engineered iPSC-derived NK Cell Product Candidate
The FT516 study is an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia (AML) and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma, and is the first-ever clinical investigation of a cell product derived from a clonal master engineered induced pluripotent stem cell (iPSC) line. Two patients, both heavily pretreated, have been treated with FT516 to date, and the first clinical findings include:
FT500 Universal, Off-the-shelf, iPSC-derived NK Cell Product Candidate
FT500 is the first iPSC-derived cell product candidate to emerge from the Company's iPSC product platform. The FT500 study is an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors. The dose-escalation stage of the study is designed to assess the safety and tolerability of three once-weekly doses of FT500, without IL-2 cytokine support, as a monotherapy and in combination with one of three FDA-approved immune checkpoint inhibitor (ICI) therapies in patients that have failed prior ICI therapy.
As of a November 28, 2019 data cutoff, 12 patients (n=8 monotherapy; n=4 in combination with ICI) have been treated with FT500, and the key clinical findings include:
Upon successful completion of the 300 million cells per dose cohort in the ICI combination arm, the Company plans to amend the current FT500 clinical protocol to include IL-2 cytokine support with each dose of FT500 and enrich for cancers that are expected to be amenable to NK cell anti-tumor activity. In the dose-expansion stage of the FT500 Phase 1 study, FT500 will be administered at 300 million cells per dose in combination with ICI therapy under this revised clinical protocol.
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.
FT500 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line. The product candidate is being investigated in an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors (clinicaltrials.gov ID number NCT03841110). The study is designed to assess the safety and tolerability of three once-weekly doses of FT500 as a monotherapy and in combination with one of three FDA-approved immune checkpoint inhibitor (ICI) therapies - nivolumab, pembrolizumab or atezolizumab - in patients that have failed prior ICI therapy. Despite the clinical benefit conferred by approved ICI therapy against a variety of tumor types, these therapies are not curative and, in most cases, patients either fail to respond or progress on these agents. One common mechanism of resistance to ICI therapy is associated with loss-of-function mutations in genes critical for antigen presentation. A potential strategy to overcome resistance is through the administration of allogeneic NK cells, which have the inherent capability to recognize and directly kill tumor cells with these mutations.
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 FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. In addition, ADCC is dependent on NK cells maintaining active levels of CD16 expression, and the expression of CD16 on NK cells has been shown to undergo considerable down-regulation in cancer patients, which can significantly inhibit anti-tumor activity.
About Fate Therapeutics, Inc.
Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Company's immuno-oncology product candidates include natural killer (NK) cell and T-cell cancer immunotherapies, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens with chimeric antigen receptors (CARs). The Company's immuno-regulatory product candidates include ProTmune™, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease, and a myeloid-derived suppressor cell immunotherapy for promoting immune tolerance in patients with immune disorders. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com.
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 FT516 and FT500, its ongoing and planned clinical studies, and the expected clinical development plans for 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 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 FT516 and FT500, 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 Securities and Exchange Commission, including but not limited to the Company's most recently filed periodic report, and from time to time in the Company's press releases and other investor communications. Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.
Stern Investor Relations, Inc.
Source: Fate Therapeutics, Inc.