A2 Biotherapeutics presented progress on its Tmod™ CAR T-cell clinical programs at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in November 2024, highlighting advancements in participant diversity, enrollment strategies, and early clinical data. The company is developing logic-gated cell therapies designed to selectively target tumor cells while protecting normal cells.
BASECAMP-1 Prescreening Study
An oral presentation by Dr. Julian R. Molina from Mayo Clinic detailed updates on the BASECAMP-1 prescreening study. This nationwide study aims to improve participant diversity and operational efficiency in patient recruitment for Tmod™ CAR T-cell trials. BASECAMP-1 utilizes next-generation sequencing (NGS) from Tempus AI to screen for participants with tumor-associated HLA-A*02 LOH, making them eligible for multiple Tmod™ CAR T-cell therapy trials. As of September 1, 2024, 70 participants were enrolled.
Strategies to enhance access to BASECAMP-1 include increasing the geographic distribution of study sites and leveraging NGS across both academic and community practices. Eligibility criteria have been amended to enroll patients with germline HLA-A*02:XX heterozygosity, potentially increasing enrollment of Hispanic (16%), African American (43%), and Asian and Pacific Islander (112%) participants.
EVEREST-1 Clinical Study
Poster presentations included safety and early biomarker data from EVEREST-1, a Phase 1/2 study evaluating A2B530 Tmod™ CAR T cells in adults with recurrent, unresectable, locally advanced, or metastatic CEA-positive solid tumors. The first patient was dosed in May 2023, and as of September 1, 2024, 14 patients were enrolled (4 with pancreatic cancer and 10 with colorectal cancer).
Pharmacokinetic data from 14 patients suggest a potential dose-response relationship, with higher doses correlating with increased peak expansion of Tmod™ cells. No dose-limiting toxicities, grade >3 serious adverse events, or neurotoxicity related to A2B530 were reported. Two pancreatic cancer patients have reached one-year survival post-infusion. Dose escalation is ongoing, and the maximum tolerated dose has not yet been reached. The study indicates that A2B530 has a manageable safety profile and is generally well-tolerated.
EVEREST-2 Clinical Study
An enrollment update was provided for EVEREST-2, a Phase 1/2 study assessing A2B694 in adult patients with solid tumors. The first patient was enrolled in April 2024, and dose escalation is currently underway. EVEREST-2 is evaluating the safety and efficacy of A2B694, a Tmod™ CAR T-cell therapy targeting mesothelin (MSLN).
About Tmod™ Platform
The Tmod™ platform employs a dual-receptor system, featuring an activator and a blocker, to selectively target tumor cells while protecting normal cells. The activator recognizes antigens on tumor cells, triggering their destruction, while the blocker recognizes antigens on normal cells, preventing off-target toxicity. A2B530 targets carcinoembryonic antigen (CEA), and A2B694 targets mesothelin (MSLN), both utilizing HLA-A*02 as the blocker target.
