Fate Therapeutics, Inc. announced the initiation of enrollment for its Phase 1 clinical trial of FT825 /ONO-8250, a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell product candidate targeting human epidermal growth factor receptor 2 (HER2). The iPSC-derived CAR T-cell product candidate incorporates a novel HER2-targeted antigen binding domain and is designed to overcome unique challenges in treating solid tumors. The Phase 1 study of FT825 /ONO-8250 is being conducted under a strategic collaboration with Ono Pharmaceutical Co.

Ltd. (Ono). Designed using the Company?s iPSC Product Platform, FT825 /ONO-8250 incorporates seven novel synthetic controls of cell function including a CXCR2 receptor to promote cell trafficking, a chimeric TGFß receptor to redirect immunosuppressive signals in the tumor microenvironment, and a high-affinity, non-cleavable CD16a receptor to enable antibody-dependent cellular cytotoxicity. Preclinical data of FT825 /ONO-8250 presented at the 2023 Society for Immunotherapy of Cancer Annual Meeting demonstrated that the profile of the novel HER2-targeted antigen binding domain is unique and differentiated from that of trastuzumab, exhibiting similar potency with greater specificity for cancer cells expressing HER2.

The Phase 1 study is designed to investigate a single dose of FT825 /ONO-8250 as monotherapy and in combination with monoclonal antibody therapy in previously-treated patients with advanced solid tumors. The dose escalation and dose expansion portions of the trial are expected to evaluate safety, tolerability, and pharmacokinetics as well as anti-tumor activity by overall response rate, duration of response and disease control rate. Under the terms of its Collaboration and Option Agreement with Ono, Fate will jointly develop and commercialize FT825 /ONO-8250 with Ono in the U.S. and Europe, and Ono maintains exclusive development and commercialization rights for FT825 /ONO-8250 in the rest of the world.

Fate is eligible to receive clinical, regulatory and commercial milestone payments as well as tiered royalties on net sales outside of the United States and Europe by Ono. The parties are currently conducting preclinical development of an additional solid tumor program targeting an undisclosed tumor-associated antigen.