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:

  • FT516 First AML Patient. The first patient enrolled for the treatment of AML was refractory to initial 7+3 induction therapy, multiple subsequent re-induction attempts with chemotherapy, and a combination therapy of venetoclax plus decitabine. Following outpatient lympho-conditioning, the patient received a first cycle of three once-weekly doses of FT516 (90 million cells per dose) as a monotherapy and IL-2 cytokine support. A bone marrow biopsy obtained at Day 42 following the completion of the first FT516 treatment cycle showed no morphologic evidence of leukemia and evidence of hematopoietic recovery. Concurrently, no circulating leukemia cells were observed in the peripheral blood, and the patient showed neutrophil recovery without growth factor support (>1,000 per µL). In addition, no dose-limiting toxicities (DLTs), Grade ≥3 adverse events (AEs) or serious adverse events (SAEs) related to FT516 were reported. The patient is expected to receive a second FT516 treatment cycle of three once-weekly doses of FT516. A formal response assessment will be performed following completion of this second FT516 treatment cycle.
  • FT516 First Lymphoma Patient. Prior to treatment with FT516, the first patient enrolled with high-risk diffuse large B-cell lymphoma (DLBCL) having relapsed after multiple rituximab combination regimens, autologous hematopoietic stem cell transplant, and chimeric antigen receptor (CAR) T-cell therapy. Following outpatient lympho-conditioning, the patient received a first cycle of three once-weekly doses of FT516 (30 million cells per dose) in combination with rituximab and IL-2 cytokine support. A second treatment cycle of three once-weekly doses of FT516 in combination with rituximab has been initiated. A formal response assessment will be performed following completion of this second FT516 treatment cycle.

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:

  • Safety. No DLTs, FT500-related SAEs or FT500-related Grade ≥3 AEs, and no incidents of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, have been reported in 12 patients.
  • Tolerability. All 12 patients completed the first FT500 treatment cycle of three once-weekly doses. Nine of 11 patients initiated a second FT500 treatment cycle, with eight of nine patients having completed the second FT500 treatment cycle. One patient is currently pending initiation of a second FT500 treatment cycle. The multi-dose, two-cycle treatment schedule was well-tolerated, and no treatment discontinuations were due to AEs.
  • Anti-FT500 T-cell Mediated Immunogenicity. The T-cell compartment of nine patients was evaluated for T-cell mediated host-versus-product allo-reactivity. A TCR repertoire analysis conducted at multiple time points following treatment with FT500 demonstrated that a maximum of up to 6% of the T-cell clones in the patients’ reconstituted T-cell compartment were comprised of pre-existing low-frequency T-cell clones, suggesting that a robust T-cell response against FT500 was not evident. As a point of contrast, in subjects undergoing immunization for infectious disease, it is observed that almost 90% of the T-cell clones that emerge existed in low frequency prior to immunization.
  • Anti-FT500 B-cell Mediated Immunogenicity. The antibody repertoire of 11 patients was analyzed for targeting of the six HLA class I types expressed by FT500 to assess B-cell mediated host-versus-product allo-reactivity. Among the 11 patients, a single FT500 anti-HLA antibody with a mean fluorescence intensity (MFI) level of ≥ 5,000 was detected in a single patient, suggesting that a robust anti-FT500 B-cell response was not evident. As a point of reference, in patients undergoing haplo-identical hematopoietic stem cell transplant, an MFI level ≥ 5,000 has been correlated with a 5-fold increase in risk of graft rejection.
  • FT500 Anti-tumor Activity. In the monotherapy arm, two of three patients in the 100 million cells per dose cohort and two of five patients in the 300 million cells per dose cohort achieved a best overall response of stable disease per iRECIST. In the ICI combination arm, two of three patients in the 100 million cells per dose cohort achieved a best overall response of stable disease per iRECIST. A fourth patient in the ICI combination arm is currently undergoing treatment in the 300 million cells per dose cohort.

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.

About FT500
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.

About FT516
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.

Forward-Looking Statements
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.

Contact:
Christina Tartaglia
Stern Investor Relations, Inc.
212.362.1200
christina@sternir.com