A2 Bio Begins Dosing in EVEREST-2 Phase 1 Trial of Mesothelin CAR T

A2 Biotherapeutics, Inc. (A2 Bio), a company specializing in clinical-stage cell therapies for solid tumors, has announced the commencement of patient dosing in its Phase 1 clinical trial for A2B694. This multi-center trial, known as EVEREST-2 (NCT06051695), aims to evaluate the safety and determine the recommended dosage of A2B694 in patients with solid tumors that express mesothelin. These tumors include ovarian, mesothelioma, pancreatic, colorectal, and non-small cell lung cancer types, particularly in patients who have lost the HLA-A*02 gene expression.

A2B694 represents the second autologous cell therapy developed by A2 Bio using its proprietary Tmod™ platform. The Tmod™ platform incorporates a dual-receptor mechanism, consisting of an activator targeting tumor cells and a blocker that safeguards normal cells. This innovative design aims to selectively eliminate tumor tissues that express mesothelin while preserving normal cells that exhibit HLA-A*02. This approach addresses a critical challenge in solid tumor treatments—the ability to target and kill only tumor cells while protecting normal ones.

Dr. William Go, the Chief Medical Officer of A2 Bio, expressed enthusiasm about the initiation of this trial, highlighting the potential of A2B694 to offer a precise and novel CAR T therapy for patients with mesothelin-expressing solid tumors who currently lack curative treatment options. He acknowledged the limited and often toxic nature of existing treatments for these patients, which are typically palliative in cases of recurrent, unresectable, locally advanced, or metastatic cancers. Dr. Go extended gratitude to the participating patients, investigators, and clinical care providers involved in the trial.

In addition to A2B694, A2 Bio is advancing the clinical development of A2B530 and other preclinical programs as part of their ongoing pipeline expansion efforts leveraging the Tmod™ platform.

EVEREST-2 is a seamless Phase 1/2 study for A2B694, an autologous logic-gated investigational cell therapy developed from A2 Bio’s Tmod™ platform. This platform ensures the selective killing of tumor cells while protecting normal cells through a dual-receptor design, featuring an activator that targets mesothelin and a blocker that identifies HLA-A*02. The loss of HLA-A*02 in tumor cells and its presence in normal cells within the eligible patient population is a critical aspect of the study. The trial is actively recruiting patients with lung, colorectal, pancreatic, ovarian, and mesothelioma cancers.

A2 Bio’s Tmod™ platform is a pioneering precision-targeting cellular system that incorporates two receptors—an activator and a blocker—to direct immune cells specifically at tumors, thereby distinguishing them from normal tissues. The activator receptor recognizes antigens on tumor cells, triggering their destruction, while the blocker receptor identifies antigens on normal cells and prevents their targeting. This blocker technology enables precise, personalized, and effective T cell targeting, allowing Tmod™ cells to discern and eliminate tumor cells without harming normal tissues.

A2 Biotherapeutics, Inc. is a clinical-stage biotech company dedicated to developing first-in-class logic-gated cell therapies to meet the significant unmet needs in cancer treatments. The company’s Tmod™ cell therapy platform is designed to address the fundamental challenge in cancer treatment—differentiating between tumor and normal cells.