A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing innovative logic-gated cell therapies to selectively target tumor cells while sparing normal cells, today presented updates on its Tmod™ CAR T-cell clinical programs at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), held November 8-10, 2024. In an oral presentation, A2 Bio highlighted progress in expanding participant diversity in the nationwide BASECAMP-1 prescreening study for Tmod™ CAR T-cell trials. The company also showcased posters featuring early safety and biomarker data from the ongoing EVEREST-1 clinical study, provided an enrollment update for EVEREST-2, and shared new strategies to enhance the potency and selectivity of its Tmod™-based precision therapies.
A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage company developing precision logic-gated CAR T-cell therapies, today highlighted key advances in its Tmod™ CAR T-cell clinical programs at the 2024 Annual Meeting of the Society for Immunotherapy of Cancer (SITC). During the event, A2 Bio shared updates on its BASECAMP-1 prescreening study, its EVEREST-1 and EVEREST-2 clinical trials, and advancements in its approach to enhancing the potency and selectivity of Tmod™ therapies.
BASECAMP-1 Study Recognized by SITC
The BASECAMP-1 abstract (#589), titled “BASECAMP-1 is an efficient pre-screening study that identifies patients with HLA LOH and provides mutational, RNA-Seq, and microbiome data for precision logic-gated CAR T therapeutic trials,” was recognized by SITC as one of the top 100 abstracts of the meeting.
A2 Bio’s Chief Medical Officer, Dr. William Go, remarked, “We are pleased to present our progress at SITC 2024 as we advance our innovative Tmod™ CAR T-cell therapies to help patients with some of the most challenging cancers. Our new participant-recruitment model aims to improve safety, efficiency, and diversity in clinical trials for Tmod™ precision therapies.”
Innovative Tmod™ Platform
The Tmod™ platform addresses the issue of on-target, off-tumor toxicity through a dual-receptor system, targeting both tumor antigens and normal tissue blockers. The blocker recognizes antigens only present on normal tissues, ensuring tumor selectivity. A2 Bio is sponsoring two Tmod™ therapies: A2B530 for carcinoembryonic antigen (CEA) in the EVEREST-1 trial and A2B694 for mesothelin (MSLN) in the EVEREST-2 trial. Both therapies are being tested in ongoing clinical studies, with patient enrollment facilitated by the BASECAMP-1 prescreening study.
BASECAMP-1 uses artificial intelligence (AI) and precision diagnostics from Tempus AI to identify patients with HLA-A*02 loss of heterozygosity (LOH), streamlining participant selection for A2 Bio’s Tmod™ trials.
BASECAMP-1 Oral Presentation
In an oral presentation, Dr. Julian R. Molina of Mayo Clinic outlined the progress of the BASECAMP-1 prescreening study, emphasizing its novel approach to improving diversity and operational efficiency in clinical trial recruitment. BASECAMP-1 uses next-generation sequencing (NGS) to identify patients with HLA-A*02 LOH, a biomarker that is present in tumor cells but not normal cells. The study aims to expand participant diversity, with recent updates allowing for broader inclusion of ethnic and racial groups. This has led to an increase in Hispanic (16%), African American (43%), and Asian/Pacific Islander (112%) enrollment.
As of September 1, 2024, 70 participants have been enrolled in BASECAMP-1, and the study continues to gather valuable data to enhance the understanding of tumor biology in patients with and without LOH.
Dr. Molina noted, “The data from BASECAMP-1 will enable faster and more efficient patient recruitment for Tmod™ trials across leading academic centers nationwide. We’re expanding geographic reach and leveraging NGS technology to include more academic and community-based practices in the process.”
EVEREST-1 Update
In a poster presentation, Dr. Patrick M. Grierson of Washington University in St. Louis shared safety and early biomarker data from the ongoing EVEREST-1 study (Abstract #588). EVEREST-1 is a first-in-human, phase 1/2 study evaluating A2B530 Tmod™ CAR T-cells in patients with CEA-expressing solid tumors, including colorectal, pancreatic, and non-small cell lung cancers.
As of September 1, 2024, 14 patients have been enrolled, including patients with colorectal and pancreatic cancers. Initial results show no dose-limiting toxicities or grade >3 adverse events, and there have been no cases of neurotoxicity. Notably, two patients with pancreatic cancer have reached one-year survival post-infusion. A dose-response trend has been observed, with higher doses leading to increased expansion of Tmod™ cells. The study is ongoing, with dose escalation continuing.
EVEREST-2 Update
Dr. Molina also provided an enrollment update for EVEREST-2 (Abstract #627), the phase 1/2 trial investigating A2B694 Tmod™ CAR T-cells for mesothelin-targeting in solid tumors. The first patient was enrolled in April 2024, and the study is in its early stages of dose escalation.
About EVEREST-1
EVEREST-1 (NCT05736731) is a seamless Phase 1/2 study investigating the safety and efficacy of A2B530, an autologous Tmod™ CAR T-cell therapy targeting CEA in patients with non-small cell lung, colorectal, and pancreatic cancers. The Tmod™ platform uses a dual-receptor system to selectively target tumor cells while sparing normal tissue.
