A2 Bio Highlights Progress of CAR T-Cell Clinical Programs in Three Poster Presentations during the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting

Presentations Detail Ongoing CEA and Mesothelin Phase 1/2 Clinical Trials In Progress Evaluating Investigational Tmod™ CAR T-Cell Therapies for Patients with Solid Tumors

Additional Poster Demonstrates Impact of Expanded Biomarker Prescreening to Improve Diversity in Clinical Trials

A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies for solid tumors, will present updates on three ongoing clinical trials in poster presentations during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. A2 Bio will present two Trials in Progress posters on its first-in-human (FIH) Phase 1/2 studies, EVEREST-1 and EVEREST-2, as well as a poster highlighting how a greater understanding of the structure of Tmod™ allowed the BASECAMP-1 master prescreening study to increase the ethnic and racial diversity of patients enrolled in its clinical trials.

“Diversity in clinical studies is essential to address racial and ethnic groups who are often underrepresented in clinical trials, especially in precision medicine studies using genetic data. We are creating the future of precision medicine by applying advanced bioinformatics in our BASECAMP-1 prescreening protocol to efficiently screen patients for enrollment in these ongoing CAR T-cell clinical trials. Expanding the enrollment criteria to include all HLA-A*02 patients will further enhance the diversity in our trial,” said Julian R. Molina, M.D., Ph.D., Professor of Oncology, Mayo Clinic, Rochester, MN.

Significant challenges remain in harnessing the potential of cell-based therapies due to a lack of tumor‑specific targets that discriminate cancer from normal cells, resulting in on‑target, off‑tumor toxicity. The investigational therapies being studied by A2 Bio in EVEREST-1 (A2B530 targeting carcinoembryonic antigen [CEA]) and EVEREST-2 (A2B694 targeting mesothelin [MSLN]) apply the company’s proprietary Tmod™ platform which utilizes a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells to provide selective tumor killing.¹

“We are encouraged by the clinical trial progress presented during ASCO 2024. A2 Bio is advancing the clinical development of our innovative CAR T-cell therapies and pioneering a new model for enhancing safety, efficiency and diversity in our interventional trials, and therefore addressing important unmet medical needs,” said William Go, M.D., Ph.D., chief medical officer of A2 Bio.

The poster presentations are scheduled on Saturday, June 1, 9:00 am – 12:00 pm CT.

EVEREST-1 (NCT05736731) is a FIH study evaluating A2B530 in patients with solid tumors that express CEA and have human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH). The first patient in EVEREST-1 was dosed in May 2023 and dose escalation continues, with 10 patients treated to date.

EVEREST-2 (NCT06051695) is also a FIH study evaluating A2B694 in patients with solid tumors that express MSLN and have HLA-A*02 LOH. The first patient was dosed in May 2024 in this study to evaluate the safety and efficacy of A2B694.

BASECAMP-1 (NCT04981119) is a master prescreening, precision medicine study identifying patients with unresectable, advanced or metastatic solid tumors with HLA-A*02 LOH; patients undergo leukapheresis and Tmod™ CAR T cells are manufactured for patients who may enroll in the ongoing EVEREST-1 and EVEREST-2 clinical trials. BASECAMP-1 enrollment began with screening for patients with the HLA-A*02:01 allele only. Nonclinical testing determined that the Tmod™ blocker was effective against other HLA-A*02:XX alleles, and enrollment was expanded to patients with any HLA-A*02 allele subtype. Because HLA-A*02:XX subtypes are more prevalent in non-whites, this change improved the racial and ethnic diversity of the BASECAMP-1 study population. By expanding enrollment, 16% more Hispanic, 43% more African-American, and 112% more Asian or Pacific Islander patients were identified.

For more information on A2 Bio clinical trials, please visit https://www.a2bioclinicaltrials.com/

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 EVEREST-1

EVEREST-1 (NCT05736731) is a seamless Phase 1/2 study for A2B530, 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. A2B530 consists of an activator that targets carcinoembryonic antigen (CEA) 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 non-small cell lung, colorectal and pancreatic cancers.

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 non-small cell lung, colorectal, pancreatic, ovarian and mesothelioma cancers.

About BASECAMP-1

BASECAMP-1 (NCT04981119) is a prescreening study to identify patients for potential treatment in A2 Bio’s clinical trials. It is a novel approach to help optimize patient treatment outcomes by enabling patients' immune cells to be banked in their healthiest state earlier in their course of cancer treatment. Next-generation sequencing is used to identify patients who have lost HLA-A*02, the biomarker of interest for A2 Bio’s studies. Patients then undergo leukapheresis to collect, process, and store patient T cells for future Tmod™ CAR T cell therapy. BASECAMP-1 is currently enrolling patients with non-small cell lung, colorectal, pancreatic, ovarian and mesothelioma cancers.

About A2 Biotherapeutics

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 Breanna DiAndreth, Agnes E. Hamburger, Han Xu, Alexander Kamb: The Tmod cellular logic gate as a solution for tumor-selective immunotherapy. Clinical Immunology, Volume 241, 2022, 109030.

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A2 Bio is advancing the clinical development of our innovative CAR T-cell therapies and pioneering a new model for enhancing safety, efficiency and diversity in our interventional trials, and therefore addressing important unmet medical needs.