BARCELONA, Spain--(BUSINESS WIRE)--#BASECAMP1--A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies for solid tumors, today announced the presentation of early efficacy and safety data from the EVEREST-2 study (NCT06051695) during the IASLC 2025 World Conference on Lung Cancer (#WCLC25) hosted by the International Association for the Study of Lung Cancer (IASLC).
In a poster presentation on September 9, Salman R. Punekar, M.D., assistant professor of medicine, NYU Langone, Perlmutter Cancer Center, will share data from the EVEREST-2 study (poster number P3.18.87) during the Clinical Trials in Progress session from 10:00 to 11:30 CEST. EVEREST-2 is a first-in-human, open-label, phase 1/2 study evaluating the safety and efficacy of A2B694 in adult patients with recurrent or metastatic solid tumor cancers expressing mesothelin (MSLN) and tumor-associated HLA-A*02 loss of heterozygosity (LOH)1.
“Mesothelin is a promising cancer therapy target, but to date, mesothelin-targeted therapies have been limited by unacceptable toxicities and death. We are very encouraged by the findings from the ongoing EVEREST-2 study, which demonstrate that A2B694, a first-in-class logic-gated cell therapy, is well tolerated and holds promise for patients with mesothelin-expressing solid tumors. Further updates will be presented at an upcoming medical congress,” Dr. Punekar said.
These early findings from the first two dose levels of EVEREST-2 in patients with advanced solid MSLN-expressing tumors with HLA-A*02 LOH are evidence that A2B694 has manageable safety and tolerability in patients with advanced solid mesothelin-expressing tumors with HLA-A*02 LOH. All patients exhibited CAR T expansion, and the dose escalation phase continues to enroll patients. More information about the EVEREST-2 study is available at https://www.a2bio.com/clinical-trials/.
EVEREST-2 Poster Summary
As of March 6, 2025, five patients were enrolled in phase 1: four women and one man, with a median age of 59 years, including four non-Hispanic White and one Hispanic patients. Tumor types included three patients with ovarian cancer; one patient with pancreatic cancer; and one patient with non-small cell lung cancer. A2B694 doses were 0.5×108 (n=1), 1×108 (n=3), and 2×108 (n=1) cells.
Lymphodepletion was well tolerated by all patients, with no clinically significant cytopenias. All patients had at least one adverse event (AE); the most common AEs were decreased appetite (n=3, 1 serious), and fatigue (n=3). There were no dose-limiting toxicities, cytokine release syndrome, or related neurotoxicity, and no new safety signals after 8.9 months of follow-up. A2B694 was detected post-infusion in peripheral blood in all patients and was present in a tumor biopsy in one patient 42 days post-infusion.
“A2 Bio is committed to helping patients with solid tumor cancers by advancing our promising precision cell therapies based on our Tmod™ technology platform. The encouraging findings from our EVEREST-2 study enable us to better understand the efficacy and safety profile of A2B694 as a potential therapy for patients with recurrent or metastatic mesothelin-expressing tumors. Currently, these patients have few treatment options. All of us at A2 Bio are grateful to the patients, investigators, and clinical care providers whose participation in EVEREST-2 is critical to understanding the emerging A2B694 clinical profile,” said John Welch, M.D., Ph.D., interim chief medical officer of A2 Bio.
Enabling Efficient Patient Identification Through Precision Medicine
Precision medicine enables efficient identification of patients in the A2 Bio clinical studies. Patients are enrolled in EVEREST-2 through BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA 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.2, 3
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.
About EVEREST-2
EVEREST-2 (NCT06051695) is a seamless Phase 1/2 study evaluating the safety and efficacy of A2B694, an autologous logic-gated investigational cell therapy 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 mesothelin 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 participants with colorectal cancer, pancreatic cancer, non-small cell lung cancer, ovarian cancer, mesothelioma, and other solid tumors that express mesothelin 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 Tokatlian T, Asuelime GE, Mock JY, DiAndreth B, Sharma S, Toledo Warshaviak D, Daris ME, Bolanos K, Luna BL, Naradikian MS, Deshmukh K, Hamburger AE, Kamb A. Mesothelin-specific CAR-T cell therapy that incorporates an HLA-gated safety mechanism selectively kills tumor cells. J Immunother Cancer. 2022 Jan;10(1):e003826. doi: 10.1136/jitc-2021-003826. PMID: 35091455; PMCID: PMC8804709.
2 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.
3 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.
Contacts
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