FATE Fate Therapeutics Inc

Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, today presented initial clinical and translational data from the Company’s Phase 1 study of FT522 in relapsed / refractory B-cell lymphoma at the American College of Rheumatology (ACR) Convergence being held in Washington, D.C. FT522 is the Company’s off-the-shelf, CD19-targeted chimeric antigen receptor (CAR) natural killer (NK) cell product candidate that incorporates multiple novel synthetic controls of cell function designed to target and deplete pathogenic immune cells, and is the Company’s first product candidate to integrate its alloimmune defense receptor (ADR) technology to enable effective treatment of patients without administration of intense conditioning chemotherapy. The Company is also initiating a Phase 1 study of FT522 across a basket of B cell-mediated autoimmune diseases as add-on to standard-of-care induction and maintenance regimens without administration of conditioning chemotherapy to patients.

“We are very excited with the initial data emerging from the low-dose cohorts of our FT522 Phase 1 study in B-cell lymphoma, where we have observed a favorable safety profile, complete responses with conditioning chemotherapy, and the potential of our ADR-armed CAR NK cell product candidate to functionally persist and selectively deplete pathogenic CD19+ B cells without administration of conditioning chemotherapy to patients,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “We believe these data provide compelling support for our highly-differentiated therapeutic strategy in autoimmunity, and we look forward to clinically assessing FT522 as an add-on to standard-of-care induction and maintenance regimens without administration of conditioning chemotherapy to patients.”

Initial FT522 Phase 1 Clinical and Translational Data in Relapsed / Refractory B-cell Lymphoma

The Company’s ongoing multi-center, Phase 1 clinical trial in relapsed / refractory B-cell lymphoma (NCT05950334) is assessing up to three doses of FT522 (Day 1, 4, and 8) in combination with a single dose of rituximab, with and without administration of conditioning chemotherapy to patients. As of a data cutoff date of November 8, 2024, there have been no dose-limiting toxicities (DLTs) and no events of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), or graft-versus-host disease (GvHD).

In the study’s conditioning arm (Regimen A), at the first dose level of 300 million cells per dose (A-DL1; n=6), all three patients with indolent lymphoma achieved a complete response (CR) and one patient with mantle cell lymphoma achieved a partial response (PR), while two patients with diffuse large B-cell lymphoma (DLBCL) did not respond to treatment (1 stable disease (SD); 1 progressive disease). At the second dose level of 900 million cells per dose (A-DL2; n=3), two of three patients with DLBCL achieved an overall response (1 CR; 1 PR; 1 SD). The potential for FT522 dose-dependent activity was supported by pharmacokinetics (PK), which showed a greater than 20-fold increase in median cumulative PK between the two dose levels (>80,000 copies*day/µgDNA for A-DL2 and <4,000 copies*day/µgDNA for A-DL1).

In addition, three patients have been treated without administration of conditioning chemotherapy in the study’s second arm (Regimen B), which is intended to provide a stringent assessment of the Company’s ADR technology designed to target 4-1BB+ immune cells and promote functional persistence without ablating a patient’s immune system. At the first dose level of 300 million cells per dose (B-DL1; n=3), live FT522 cells were detected in the patients’ peripheral blood through Day 15 (one week post-infusion of the third dose), demonstrating the ability of FT522 to persist in the presence of an unmatched, fully-intact immune system. Notably, in all three patients, each dose of FT522 on Day 1, 4, and 8 maintained functional activity as evidenced by a similar percent reduction in circulating CD19+ B cells in the patients’ peripheral blood with each infused dose. These first-of-kind translational data support the potential of live FT522 cells to functionally persist and deplete pathogenic CD19+ B cells without administration of conditioning chemotherapy to patients.

FT522 Phase 1 Basket Study in B cell-mediated Autoimmune Diseases

The Company’s Phase 1 study is designed to assess the safety, pharmacokinetics, and activity of FT522 across a basket of B cell-mediated autoimmune diseases, including anti-neutrophilic cytoplasmic antibody-associated vasculitis (AAV), idiopathic inflammatory myositis (IMM), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). The Phase 1 study is intended to treat patients with up to four doses of FT522, without administration of conditioning chemotherapy, as an add-on to rituximab induction therapy (Regimen A) and as an add-on to maintenance therapy in combination with rituximab (Regimen B). Dose escalation is expected to commence at 900 million cells per dose.

In a preclinical in vivo biodistribution study, FT522 showed dose-dependent trafficking, infiltration, and residency in primary, secondary, and tertiary tissues without cytokine support at human dose equivalency levels of 250 million cells per dose and 1 billion cells per dose (based on 20 gram mouse and 65 kilogram human allometric conversion). In addition, in an in vitro re-challenge assay using peripheral blood mononuclear cells (PBMCs) from unmatched SLE donors, FT522 uniquely drove rapid and deep CD19+ B cell depletion, maintained functional persistence, and eliminated alloreactive T cells, indicating that FT522 has the potential to function effectively in the presence of an unmatched host immune system.

FT596 Phase 1 Clinical Data in Relapsed / Refractory B-cell Lymphoma

The Company also presented Phase 1 clinical data from FT596, its prior-generation CD19-targeted CAR NK cell product candidate, in relapsed / refractory B-cell lymphoma (NCT04245722). The completed study enrolled 68 heavily pre-treated patients (median of 4 prior lines of therapy) with late-stage disease (84% with Stage IV disease) who received standard three-day conditioning chemotherapy (500 mg/m2 of cyclophosphamide x 30 mg/m2 of fludarabine), a single dose of rituximab (375 mg/m2), and up to 3 doses of FT596 at dose levels ranging from 30 million cells per dose to 1.8 billion cells per dose. FT596 demonstrated a favorable safety profile, with no events of ICANS or GvHD and low incidence of low grade CRS (Grade 1 = 10%; Grade 2 = 4%; Grade ≥3 = 0). There were no FT596-related adverse events resulting in study discontinuation or death.

Durable responses across histologies were observed, with an overall and complete response rate of 100% and 85%, respectively, and median duration of response of 16.9 months, in relapsed / refractory follicular lymphoma (n=13); and an overall and complete response rate of 38% and 25%, respectively in relapsed / refractory large B-cell lymphoma (n=32), where median duration of response was not reached. Notably, CD19+ B-cell counts in the peripheral blood of patients showed rapid, deep, and sustained depletion through the first month of treatment. Publication of the FT596 Phase 1 study is in press (Ghobadi, A. et al., Phase 1 study of iPSC-derived CD19-directed CAR NK cells in B-cell lymphoma, Lancet).

About Fate Therapeutics’ iPSC Product Platform

Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications.

About Fate Therapeutics, Inc.

Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune diseases. Using its proprietary iPSC product platform, the Company has established a leadership position in creating multiplexed-engineered master iPSC lines and in the manufacture and clinical development of off-the-shelf, iPSC-derived cell products. The Company’s pipeline includes iPSC-derived natural killer (NK) cell and T-cell product candidates, which are selectively designed, incorporate novel synthetic controls of cell function, and are intended to deliver multiple therapeutic mechanisms to patients. 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 iPSC-derived CAR T-cell product candidates, including FT522 and FT596, the advancement of and plans related to the Company's product candidates, clinical studies and preclinical research and development programs, the Company’s progress, plans and timelines for the clinical investigation of its product candidates, including the expected clinical development plans for FT522 and FT596, the initiation and continuation of enrollment in the Company’s clinical trials, the initiation of additional clinical trials and additional dose cohorts in ongoing clinical trials of the Company’s product candidates, the timing and availability of data from the Company’s clinical trials, the therapeutic and market potential of the Company’s research and development programs and product candidates, the Company’s clinical and product development strategy, and the Company’s expectations regarding progress, plans, and timelines. 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 research and development programs and product candidates, including those product candidates in clinical investigation, may not demonstrate the requisite safety, efficacy, or other attributes to warrant further development or to achieve regulatory approval, 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 initiation and conduct of, or enrollment of patients in, any clinical trials, 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, changes in the therapeutic, regulatory, or competitive landscape for which the Company’s product candidates are being developed, 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 or delays in manufacturing or supplying the Company’s product candidates for clinical testing, failure to demonstrate that a product candidate has the requisite safety, efficacy, or other attributes to warrant further development, 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 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 TartagliaPrecision AQ212.362.1200christina.tartaglia@precisionaq.com