First Patient Receives AB-2100 in Phase 1/2 Trial for Clear-cell Renal Cell Carcinoma

ArsenalBio, a company in the forefront of developing advanced CAR T-cell therapies for solid tumors, has initiated a Phase 1/2 clinical trial for AB-2100, a therapy designed to target clear-cell renal cell carcinoma (ccRCC). This innovative treatment leverages the company's proprietary CITE technology, which stands for CRISPR Integration of Transgenes by Electroporation, to enhance T cells' ability to specifically target tumors while navigating the complex tumor microenvironment.

The first patient has received AB-2100 in a multi-center, open-label trial, marking a significant step in addressing the unmet medical needs of ccRCC patients. ArsenalBio's Chief Medical Officer, Dr. Susie Jun, highlighted the potential of their Integrated Circuit T (ICT) cell technology, which is expected to destroy ccRCC cells without affecting healthy tissues.

The Phase 1/2 trial, identified by the number NCT06245915, is structured as a dose escalation study to assess the safety and efficacy of AB-2100. It will include patients with ccRCC whose condition did not improve or relapsed after treatment with checkpoint inhibitors and VEGF inhibitors. The objective is to establish the maximum tolerated dose of AB-2100, which is administered intravenously following conditioning chemotherapy. The trial plans to enroll approximately 60 patients in Phase 1 and a total of 130 patients across various clinical sites in the United States.

AB-2100 is an ICT cell therapy that incorporates a sophisticated manufacturing technique involving the precise CRISPR-mediated insertion of a synthetic DNA cassette into a safe location in Chromosome 11. This cassette includes several features: a synthetic logic gate to optimize tumor targeting and avoid normal tissues by requiring the presence of two distinct proteins found in ccRCC; shRNAs to protect the T cells from immunosuppressive signals in the tumor microenvironment; and a novel synthetic pathway activator (SPA) to enhance the potency and longevity of the engineered T cells.

Dr. Jun explained that the logic gate approach is designed to selectively target tumors by requiring the presence of two antigens in close proximity. Preclinical data suggests that this synthetic biology-based approach could effectively target antigens like CA9, which traditional CAR T-cell strategies have struggled with due to on-target toxicity in healthy tissues.

AB-2100 represents ArsenalBio's second internally discovered T cell therapeutic candidate to enter clinical development. The company's first candidate, AB-1015, is currently in a phase 1 trial for the treatment of ovarian cancer.

Arsenal Biosciences, Inc., based in South San Francisco, California, is dedicated to discovering and developing next-generation autologous T cell therapies to combat cancer. The company's comprehensive R&D engine aims to create multifunctional T cell medicines through precise CRISPR-mediated DNA insertion. ArsenalBio is committed to building a robust DNA library for therapeutic enhancement, integrating logic gating for improved tumor targeting and synthetic features for multiple pharmaceutical functions. The company is pioneering a computationally driven approach combined with nonviral clinical manufacturing, with the goal of delivering more effective treatments, enhancing patient safety, reducing costs, and expanding market access.