A2 Bio Announces First Patient Dosed in EVEREST-2 Phase 1 Clinical Trial of Novel Mesothelin Logic-Gated CAR T

First-in-human trial of A2B694 uses A2 Bio’s logic-gated Tmod™ platform for cell therapies to provide selective killing of tumor cells while protecting normal cells

A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies for solid tumors, today announced dosing of the first patient in the Phase 1 clinical trial of A2B694. The multi-center Phase 1 dose escalation clinical trial, EVEREST-2 (NCT06051695), will evaluate safety and determine the recommended dose of A2B694 in patients with solid tumors that express mesothelin, including ovarian, mesothelioma, pancreatic, colorectal and non-small cell lung cancer, and have lost HLA-A*02 expression.

A2B694 is the second autologous cell therapy in clinical development by A2 Bio using its proprietary Tmod™ platform. The Tmod™ platform utilizes a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. This dual-receptor design is intended to provide selective killing of tumor tissues that express mesothelin and have lost the HLA-A*02 gene permanently. This novel design is aimed at tackling the fundamental challenge in solid tumor cancer medicines – the ability to selectively kill tumor cells and protect normal cells.

“Dosing our first patient in this trial is a key step to provide a precise, novel CAR T therapy to patients with solid tumors that express mesothelin with no curative treatment options. Sadly, current treatment options for these patients are palliative and limited by toxicity in the recurrent, unresectable, locally advanced or metastatic setting. All of us at A2 Bio would like to thank participating patients, investigators, and clinical care providers,” said Dr. William Go, chief medical officer of A2 Bio.

​​In addition to A2B694, A2 Bio continues to advance its clinical development of A2B530 as well as other preclinical programs as the company pursues additional pipeline expansion opportunities using its proprietary Tmod™ platform.

About EVEREST-2

EVEREST-2 (NCT06051695) is a seamless Phase 1/2 study for A2B694, an autologous logic-gated investigational cell therapy developed from A2 Bio’s proprietary Tmod™ platform. The Tmod™ platform provides selective killing of tumor cells and protection of normal cells via a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. A2B694 consists of an activator that targets mesothelin (MSLN) and a blocker that targets HLA-A*02. HLA-A*02 is lost in tumor cells and present in normal cells in the eligible patient population. The study is recruiting patients with lung, colorectal, pancreatic, ovarian and mesothelioma cancers.

About the Tmod™ Platform

A2 Bio has pioneered a precision-targeting cellular system – the Tmod™ mechanism – that incorporates two receptors, an activator and a blocker, to aim the powerful armaments of immune cells directly at tumors to unequivocally differentiate tumors from normal tissues. The activator recognizes antigens on tumor cells that trigger their destruction, while the blocker recognizes antigens on normal cells that protect them. This novel blocker technology enables precise, personalized and effective T cell targeting. The blocker component equips Tmod™ cells with the capacity to identify tumors as distinct from normal cells.

About A2 Bio

A2 Biotherapeutics, Inc. (A2 Bio) is a clinical-stage biotech company developing first-in-class logic-gated cell therapies to address the high unmet need in cancers. A2 Bio invented the proprietary Tmod™ cell therapy platform to tackle the fundamental challenge in cancer treatment—the ability of cancer medicines to distinguish between tumor and normal cells. For more information, please visit the company’s website at www.a2bio.com.

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“Dosing our first patient in this trial is a key step to provide a precise, novel CAR T therapy to patients with solid tumors that express mesothelin with no curative treatment options."