Fate Therapeutics Showcases FT825/ONO-8250 CAR T-cell for Advanced Tumors at 2024 SITC Meeting

Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company, revealed preliminary clinical and preclinical data for its new CAR T-cell candidate, FT825 / ONO-8250, which targets the HER2 protein, at the 2024 Society of Immunotherapy of Cancer (SITC) Annual Meeting. The ongoing Phase 1 study focuses on advanced solid tumors and includes a cohort of three patients who received low doses of FT825 / ONO-8250 as a monotherapy. Remarkably, the study observed no dose-limiting toxicities (DLTs) or adverse events such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD).

Scott Wolchko, President and CEO of Fate Therapeutics, expressed optimism about the initial findings, citing the favorable safety profile and the observed maintenance of an activated CAR T-cell state in the patients. The company, in collaboration with Ono Pharmaceutical Co., Ltd., plans to further explore the potential of FT825 / ONO-8250 for treating difficult-to-treat advanced solid tumors.

The Phase 1 study aims to evaluate the safety, pharmacokinetics, and efficacy of FT825 / ONO-8250 both as a monotherapy and in combination with monoclonal antibody (mAb) therapies in patients with advanced solid tumors. The preliminary data presented at SITC involved three patients who had previously undergone extensive treatments, including HER2-targeted therapies. These patients received a conditioning chemotherapy regimen followed by a 100 million cell dose of FT825 / ONO-8250. Notably, peak CAR T-cell expansion was observed on Day 8 post-treatment, with no signs of exhaustion in the CAR T-cells.

As of October 25, 2024, the treatment was well-tolerated in the initial cohort, prompting ongoing enrollment at higher dose levels. The study also includes evaluating the combination of the CAR T-cell therapy with EGFR-targeted mAb therapies.

FT825 / ONO-8250 incorporates a novel H2CasMab-2 antigen binding domain specifically designed to target HER2-positive cancer cells while minimizing the risk of off-tumor toxicity. This novel binding domain enables the CAR T-cells to recognize and attack HER2 variants that are often associated with poor clinical outcomes and tumor resistance to existing therapies. The preclinical data presented underscored the robust, HER2-specific anti-tumor activity of FT825 / ONO-8250, both in vitro and in vivo, with limited impact on HER2-expressing normal cells.

The development and commercialization of FT825 / ONO-8250 are being jointly pursued by Fate Therapeutics and Ono Pharmaceutical Co., Ltd. The companies are also working on another solid tumor program targeting a different, undisclosed tumor-associated antigen. This collaboration grants Fate and Ono shared responsibilities for development and commercialization in the U.S. and Europe, while Ono retains exclusive rights in the rest of the world.

Fate Therapeutics leverages its proprietary iPSC product platform to create clonal master iPSC lines, which serve as the foundation for manufacturing engineered cell products. These products are well-defined, uniform, and can be stored for off-the-shelf availability, facilitating broad patient access. The platform aims to overcome various limitations inherent in cell therapies derived from patient or donor cells, offering a promising avenue for treating cancer and autoimmune diseases.

The company’s pipeline includes iPSC-derived NK cell and T-cell product candidates, designed to incorporate synthetic controls of cell function for enhanced therapeutic mechanisms. Fate Therapeutics is headquartered in San Diego, CA, and continues to advance its position in the field of iPSC-derived cellular immunotherapies.