AGOURA HILLS, Calif. — A2 Biotherapeutics Inc. said it has dosed the first patient with A2B543, launching the second arm of its Phase 1/2 EVEREST-2 clinical trial evaluating the company’s logic-gated CAR T cell therapy for solid tumors.
A2B543 is an autologous CAR T therapy built on A2 Bio’s proprietary Tmod platform. The therapy incorporates an inducible, membrane-tethered IL-12 booster designed to enhance antitumor activity while maintaining the platform’s selective targeting approach, which aims to kill tumor cells while protecting normal tissue.
“Dosing the first patient with A2B543 is a significant step forward in the evolution of the Tmod platform,” said John Welch, M.D., Ph.D., chief medical officer of A2 Bio. “While systemic IL-12 induces a potent antitumor immune response, its use has been limited by severe toxicity. With A2B543, we are arming our Tmod cells with a membrane-tethered, inducible IL-12 component. This design allows us to localize the impact of IL-12 to the tumor microenvironment, boosting the persistence and potency of Tmod without the systemic side effects.”
The membrane-tethered IL-12 component is engineered to activate only when the Tmod cell engages its target tumor antigen. The company said this approach is intended to strengthen the therapy’s activity within the immunosuppressive tumor microenvironment while minimizing the risk of systemic toxicity that has historically limited IL-12–based strategies.
EVEREST-2 is supported by A2 Bio’s BASECAMP-1 master prescreening study, which uses next-generation sequencing and AI-enabled precision diagnostics to identify patients with HLA loss of heterozygosity. Eligible patients may transition directly from BASECAMP-1 into EVEREST-2 as their disease progresses, without a mandatory waiting period between studies.
In addition to A2B543, A2 Bio’s clinical pipeline includes A2B694 and A2B395, along with multiple preclinical programs leveraging the Tmod platform. The company said the Tmod suite of technologies can be deployed in autologous or allogeneic settings and applied individually or in combination to develop therapies for cancer and other serious diseases.
