A2 Biotherapeutics announced the acceptance of four abstracts for presentation at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), taking place November 5-9, 2025, in National Harbor, Maryland. The presentations will showcase early clinical data from the company's innovative logic-gated CAR-T cell therapy platform designed to address the fundamental challenge of distinguishing between tumor and normal cells in cancer treatment.
EVEREST-2 Study Results
The company will present initial safety and efficacy results from EVEREST-2 (NCT06051695), a seamless Phase 1/2, open-label, nonrandomized study evaluating A2B694. This autologous logic-gated investigational cell therapy is developed from A2 Bio's proprietary Tmod™ platform and targets solid tumors expressing mesothelin with HLA-A*02 loss of heterozygosity.
Dr. Jeffrey Ward from Washington University will present the EVEREST-2 data on Friday, November 7, detailing outcomes from patients with non-small cell lung cancer, pancreatic cancer, ovarian cancer, colorectal cancer, mesothelioma, and other solid tumors that express mesothelin and have lost HLA-A*02 expression.
DENALI-1 Enrollment Update
A2 Bio will also provide an enrollment update for DENALI-1 (NCT06682793), a seamless Phase 1/2 study evaluating A2B395, an allogeneic logic-gated Tmod™ CAR T-cell product. Dr. Salman Punekar from New York University Langone Health's Perlmutter Cancer Center will present data on this therapy targeting adults with solid tumors that express EGFR and have lost HLA-A*02 expression, including non-small cell lung cancer, head and neck squamous cell carcinoma, triple-negative breast cancer, renal cell carcinoma, and colorectal cancer.
Dual-Receptor Technology Platform
The Tmod™ platform represents a precision-targeting cellular system that incorporates two receptors: an activator and a blocker. The activator recognizes antigens on tumor cells that trigger their destruction, while the blocker recognizes antigens on normal cells that protect them. This dual-receptor design enables the therapy to selectively kill tumor cells while protecting normal cells.
For A2B694, the activator targets mesothelin while the blocker targets HLA-A02, which is lost in tumor cells but present in normal cells in the eligible patient population. The A2B395 therapy uses a similar approach, with an activator targeting EGFR and the same HLA-A02 blocker mechanism.
Patient Identification Strategy
Both studies utilize BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA loss of heterozygosity through next-generation sequencing. This novel approach helps optimize patient treatment outcomes by enabling patients' immune cells to be banked in their healthiest state earlier in their course of cancer treatment. Patients eligible for autologous therapy undergo leukapheresis to collect, process, and store patient T cells for future Tmod™ CAR T cell therapy.
Platform Enhancement Research
Additional presentations will focus on approaches to boost potency and preserve selectivity of Tmod™-based precision cell therapies. These include research on genetic screens to identify novel functional modules for NOT gate technology and an inducible signal mechanism designed to overcome limited antigen access in solid tumor cell therapy.
A2 Biotherapeutics positions itself as a clinical-stage biotech company developing first-in-class logic-gated cell therapies to address high unmet needs in cancer treatment, with the Tmod™ platform specifically designed to tackle the fundamental challenge of enabling cancer medicines to distinguish between tumor and normal cells.
