On November 12, 2024 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 diseases, reported business highlights and financial results for the third quarter ended September 30, 2024 (Press release, Fate Therapeutics, NOV 12, 2024, View Source [SID1234648170]).
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"We look forward to sharing initial Phase 1 clinical data of our off-the-shelf FT819 CAR T-cell product candidate in systemic lupus erythematosus at ACR Convergence and ASH (Free ASH Whitepaper). We continue to make great strides in our pursuit of therapeutic differentiation for patients with B cell-mediated autoimmune diseases, and patient enrollment is ongoing assessing FT819 with fludarabine-free conditioning as well as in a new treatment arm as add-on to maintenance therapy without conditioning chemotherapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "In addition, we are very pleased with the Phase 1 study design allowed by the FDA for our FT522 ADR-armed CAR NK cell product candidate in autoimmunity, which is designed to assess multiple doses of FT522 without conditioning chemotherapy across a basket of B cell-mediated autoimmune diseases, and we look forward to presenting an initial look at the clinical and translational data of FT522 in B-cell lymphoma at ACR."
FT819 iPSC-derived 1XX CAR T-cell Program
•Three Patients Treated in Phase 1 Autoimmunity Study using Fludarabine-free Conditioning. The ongoing multi-center, Phase 1 clinical trial for patients with moderate-to-severe systemic lupus erythematosus (SLE) is designed to evaluate the safety, pharmacokinetics, and anti-B cell activity of FT819, the Company’s off-the-shelf CD8αβ+ T-cell product candidate that incorporates a CD19-targeted chimeric antigen receptor (CAR) with a novel 1XX costimulatory domain into the T-cell receptor alpha constant (TRAC) locus (NCT06308978). The first three patients, all of whom presented with active lupus nephritis (LN) despite having been treated with multiple standard-of-care therapies, received fludarabine-free conditioning consisting of either bendamustine alone or cyclophosphamide alone, followed by a single dose of FT819 at 360 million cells (Regimen A). All three patients remain on-study, and there have been no dose-limiting toxicities (DLTs) and no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD). The Company plans to present clinical and translational data from the first three patients at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in San Diego, CA on December 7-10.
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First SLE Patient Case Study to be Presented at ACR Convergence. The first patient treated in the ongoing FT819 Phase 1 Autoimmunity study was a 27 year-old woman diagnosed with LN over ten years ago who received fludarabine-free conditioning followed by a single dose of FT819 at 360 million cells. The first patient has completed six-month follow-up and remains on-study. The Company plans to present clinical and translational data from the first patient at the American College of Rheumatology (ACR) Convergence being held in Washington, D.C. on November 16-19.
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Initiated Second Treatment Arm Adding FT819 to Maintenance Therapy without Conditioning. The Company amended the clinical protocol of its FT819 Phase 1 Autoimmunity study to include a second treatment arm (Regimen B) to assess the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 as an add-on to maintenance therapy without conditioning chemotherapy in patients with SLE. The new arm is open for enrollment at a starting cell dose of 360 million cells, and is being conducted in parallel with Regimen A.
FT825 / ONO-8250 iPSC-derived CAR T-cell Program
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Initial Phase 1 Clinical Data Presented at 2024 SITC (Free SITC Whitepaper). Under its collaboration with Ono Pharmaceutical Co., Ltd. (Ono), the Company is conducting a multi-center, Phase 1 study to assess the safety, pharmacokinetics, and activity of FT825 / ONO-8250, a multiplexed-engineered CAR T-cell product candidate targeting human epidermal growth factor receptor 2 (HER2), in patients with advanced solid tumors (NCT06241456). At the 2024 Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39thAnnual Meeting, the Company presented initial clinical data from three heavily pre-treated patients, all of whom were previously treated with at least five prior lines of therapy including HER2-targeted therapy. Each patient was administered conditioning chemotherapy and a single dose of FT825 / ONO-8250 at the first dose level of 100 million cells. As of a data cutoff date of October 25, 2024, FT825 / ONO-8250 demonstrated a favorable safety profile with no DLTs and no events of any grade of CRS, ICANS, or GvHD. In addition, at Day 8 following treatment, peak CAR T-cell expansion was observed and phenotyping of FT825 / ONO-8250 sourced from the patients’ peripheral blood was indicative of an activated state (as evidenced by high levels of Granzyme B expression and maintenance of CAR expression) with no evidence of exhaustion (as evidenced by low levels of PD-1 and TIM3 expression). Enrollment is currently ongoing at the second dose level of 300 million cells as monotherapy and at the first dose level of 100 million cells in combination with epidermal growth factor receptor (EGFR)-targeted monoclonal antibody therapy.
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New Preclinical Data Demonstrates Cancer-selectivity of Novel H2CasMab-2 CAR. FT825 / ONO-8250 incorporates seven synthetic controls of cell function including a novel cancer-selective H2CasMab-2 CAR, which has exhibited similar potency with greater specificity for cancer cells expressing HER2 compared to trastuzumab in preclinical studies. New preclinical data presented at SITC (Free SITC Whitepaper) demonstrated potent HER2-specific, anti-tumor activity in both in vitro and in vivo settings with limited cytolytic
targeting of HER2+ normal cells. The on-tumor selectivity of FT825 / ONO-8250 was attributed to its incorporation of a novel HER2-targeted antigen binding domain, which was derived from a cancer-specific monoclonal antibody H2CasMab-2 (Kaneko et al., 2024), that was shown to differentially and preferentially recognize both locally misfolded HER2 and p95 truncation variants of HER2 as compared to trastuzumab.
FT522 iPSC-derived CAR NK Cell Program
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Initial Clinical Data from Phase 1 BCL Study to be Presented at ACR Convergence. FT522 is the Company’s off-the-shelf, CD19-targeted CAR NK cell product candidate and its first to incorporate Alloimmune Defense Receptor (ADR) technology, which is designed to reduce or eliminate the need for administration of conditioning chemotherapy to patients receiving cell therapies. In its ongoing multi-center, Phase 1 clinical trial of FT522 in patients with relapsed / refractory B-cell lymphoma (BCL) (NCT05950334), the Company is currently enrolling patients in the second three-dose cohort at 900 million cells per dose with conditioning chemotherapy (Regimen A) and in the first three-dose cohort at 300 million cells per dose without conditioning chemotherapy (Regimen B). No DLTs, and no events of any grade of CRS, ICANS, or GvHD, have been reported in the Phase 1 study. The Company plans to present initial clinical and translational data from the Phase 1 BCL study at ACR Convergence.
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IND Application for Phase 1 Basket Study in Autoimmunity Allowed by FDA. The U.S. Food and Drug Administration (FDA) has allowed the Company’s Investigational New Drug (IND) application to assess the safety, pharmacokinetics, and activity of FT522 across a basket of B cell-mediated autoimmune diseases. The Phase 1 study is intended to treat patients with multiple doses of FT522 without 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. The Company previously presented preclinical data from a novel re-challenge assay using peripheral blood mononuclear cells (PBMCs) from unmatched SLE donors, showing that 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.