A2 Biotherapeutics Announces FDA Clearance of IND for A2B543 for Treatment of Adults with Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors that Express Mesothelin and Have Lost HLA-A*02 Expression

• Boosted CAR: A2B543 is enhanced with a membrane-tethered IL-12 booster to augment therapeutic potency
• Robustness: Tmod platform continues to demonstrate selectivity against cancer and adaptability to new technological components

AGOURA HILLS, Calif.–(BUSINESS WIRE)–#CART–A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies for solid tumors, today announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for A2B543 for the treatment of germline heterozygous HLA-A*02 adults with recurrent unresectable, locally advanced, or metastatic solid tumors. A2B543 contains a membrane-tethered IL-12 booster, designed to enhance potency and persistence of Tmod cells and address the immunosuppressive tumor microenvironment. It will be evaluated as a second arm of the EVEREST-2 master protocol (NCT06051695) in patients with colorectal cancer, pancreatic cancer, non-small cell lung cancer, ovarian cancer, mesothelioma, and other solid tumors that express mesothelin (MSLN) and have lost HLA-A*02 expression.

“FDA clearance of our IND for A2B543 is an important milestone for A2 Bio. Our ability to launch four clinical programs in just four years highlights the adaptability and robustness of the Tmod platform and the promising clinical pipeline of Tmod-based cell therapies. We are committed to speeding the clinical development of our therapies to help patients with solid tumors who need new treatment options,” said Jim Robinson, chief executive officer of A2 Bio.

A2 Bio continues to advance its clinical development of A2B694, A2B395, the BASECAMP-1 prescreening study, and other preclinical programs as the company pursues additional pipeline expansion opportunities using its proprietary Tmod technology platform. The Tmod platform comprises a suite of technologies that can be used in isolation or in combination, and in both autologous and allogeneic settings, to create novel therapies for cancers and beyond.

Enabling Efficient Patient Identification for A2 Bio Precision Medicine Studies

The BASECAMP-1 (NCT04981119) master prescreening study enables efficient identification of patients for all A2 Bio precision medicine studies. Patients are enrolled in EVEREST-2 through BASECAMP-1, which identifies patients with HLA loss of heterozygosity (LOH) at any time in the course of their disease via next-generation sequencing. Upon disease progression, the participant may screen for enrollment in EVEREST-2. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-2 based on their own disease course. BASECAMP-1 utilizes artificial intelligence (AI)-enabled precision diagnostics as a cost-effective, high-yield approach to identify eligible patients for all A2 Bio clinical studies.^1,2

For more information about A2 Bio clinical studies and how to enroll, visit www.a2bioclinicaltrials.com.

About A2B543

A2B543 is designed for the treatment of germline heterozygous HLA-A*02 adults with recurrent unresectable, locally advanced, or metastatic solid tumors that express MSLN and have lost HLA-A*02 expression. A2B543 is comprised of autologous Tmod cells transduced with two lentiviral vectors: one expressing both the HLA-A*02-targeted blocker and the MSLN-targeted CAR activator; and a second expressing a membrane-tethered IL-12 (memIL-12) booster. The inducible memIL-12 booster, which activates only upon engagement with tumor antigens, is designed to reduce toxicity associated with systemic IL-12 while enhancing the long-term potency and persistence of Tmod.³

About EVEREST-2

The EVEREST-2 master protocol (NCT06051695) is a seamless Phase 1/2 study evaluating the safety and efficacy of A2B694 (Arm 1) and A2B543 (Arm 2), autologous logic-gated investigational cell therapies developed from the A2 Bio 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 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. A2B543 contains the same Tmod construct as A2B694 with an added memIL-12 booster. The EVEREST-2 study is recruiting participants with colorectal cancer, pancreatic cancer, non-small cell lung cancer, ovarian cancer, mesothelioma, and other solid tumors that express MSLN and have lost HLA-A*02 expression.

About the Tmod Platform

A2 Bio has pioneered a precision-targeting cellular system – the Tmod platform – 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.

References

¹ Smith CJ, Simeone DM, Grierson PM, et al. Improving ethnic and racial diversity in biomarker-driven clinical trials: a proof of concept with the BASECAMP-1 master prescreening study of patients with high-risk solid tumors with human leukocyte antigen-A*02 (HLA-A*02) loss of heterozygosity (LOH). ASCO Annual Meeting 2024. Available at: https://www.a2bio.com/wp-content/uploads/ASCO-2024_Improving-Trial-Diversity.pdf

² Lozac’hmeur A, Danek T, Yang Q, et al. Detecting HLA loss of heterozygosity within a standard diagnostic sequencing workflow for prognostic and therapeutic opportunities. NPJ Precis Oncol. 2024;8(1):174. Available at: https://www.a2bio.com/wp-content/uploads/Detecting-HLA-LOH-Within-Diagnostic-Sequencing-npj-Precision-Oncology.pdf

³ Zhang JA, Imboden S, Lee D, et al. Onboard, tethered IL-12 boosts potency of the Tmod NOT gate and preserves selectivity. J Immunother Cancer. 2025;13(5):e010976. Available at: https://www.a2bio.com/wp-content/uploads/Onboard-tethered-IL-12-boosts-potency-of-the-Tmod-NOT-gate-and-preserves-selectivity.pdf

Contacts

Mary-Frances Faraji

Jeff Winton Associates

maryfrances@jeffwintonassociates.com
908-334-7693