• First complete response to a CAR T-cell therapy reported in a non-small cell lung cancer patient; the patient had high-risk genetic mutations and was refractory to first-line therapy
• A2B694 has manageable safety and is well tolerated, with no dose-limiting toxicities and no serious adverse events
• A2B694 demonstrates cell expansion, persistence, and tumor infiltration
• The maximum tolerated dose has not been reached; enrollment and dose escalation continue
• Data from first nine patients treated in EVEREST-2 presented at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC)

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 safety and early efficacy data from the EVEREST-2 study (NCT06051695) of its lead program, A2B694. The data was presented at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) and was recognized as a Top 150 Abstract.

The findings from EVEREST-2 include the first reported complete response (CR) in a patient with non-small cell lung cancer (NSCLC) following treatment with a CAR T-cell therapy. This patient had progressive, metastatic NSCLC with KRAS G12V/STK11 co-mutations, an aggressive subtype associated with resistance to chemoimmunotherapy and poor prognosis. The patient had also been refractory to first-line therapy. After a single infusion of A2B694, the patient achieved a CR (per RECIST 1.1) at day 90 that was confirmed by central review at day 180. Complete responses have rarely been observed in studies of CAR T-cell therapies for the treatment of solid tumors and none have been reported in patients with lung cancer.¹

“It is exciting to share the first report of a complete response to CAR T-cell therapy in a patient with a hard-to-treat case of non-small cell lung cancer. Our findings from the ongoing EVEREST-2 study demonstrate that A2B694 holds promise as a new precision cell therapy targeting mesothelin-expressing solid tumors, such as NSCLC, mesothelioma, pancreatic, ovarian, and colorectal cancer, if future studies prove successful,” said Salman R. Punekar, M.D., assistant professor of medicine, NYU Langone Health, Perlmutter Cancer Center and treating physician of this patient.

Evaluating A2B694

As of September 11, 2025, nine patients were enrolled in EVEREST-2, including three patients with ovarian cancer; two patients with pancreatic cancer; and one patient each with NSCLC, colorectal cancer, gastro-esophageal cancer, and mesothelioma. Three dose levels were administered: 1x10⁸ (n=3), 2x10⁸ (n=4), and 4x10⁸ (n=2) cells, of which one patient each at the 1x10⁸ and 2x10⁸ levels received half dose due to body weight, per clinical protocol. Maximum tolerated dose (MTD) has not been reached. Higher doses up to 14x10⁸ are planned to be evaluated in this dose-finding trial.

A2B694 Safety

A2B694 had manageable safety and was well tolerated with no dose-limiting toxicities. Lymphodepletion prior to A2B694 administration was well tolerated, with typical, transient cytopenias. There were no dose-limiting toxicities (DLTs) or cases of cytokine release syndrome (CRS). There was one case of grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), which was successfully managed. No deaths were attributed to A2B694, and no patient has discontinued the study due to adverse events.

A2B694 Pharmacokinetics

A2B694 was detected post-infusion in peripheral blood and showed cell expansion in all treated patients, and was also detected in multiple tumor biopsies. In one patient, A2B694 was detected in a tumor biopsy collected on day 42, but not in the concurrently collected blood sample, demonstrating that A2B694 can infiltrate the tumor microenvironment and persist for weeks, even when undetectable in the peripheral blood.

Case Report of Complete Response in NSCLC patient

A patient with co-mutated (KRAS G12V/STK11) NSCLC, a subtype associated with resistance to chemoimmunotherapy and poor prognosis, had progressed on standard-of-care first-line treatment of carboplatin, pemetrexed, and pembrolizumab before enrolling in EVEREST-2. At day 90 post-infusion of A2B694, the patient achieved a complete response (CR) per RECIST 1.1 and had a confirmed CR by central review at day 180. PET-CT scan on day 190 showed no evidence of disease. Longitudinal ctDNA tests that detected tumor mutations at diagnosis showed no detections of those same mutations post-treatment at month 6 and again at month 8. On day 243, the patient had an isolated CNS relapse, with an ongoing non-CNS CR per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM). The patient was treated with dexamethasone and definitive gamma knife radiosurgery. Subsequent PET-CT demonstrated continued absence of disease on day 284. At month 12, the patient's CT showed no new findings.

Enabling Efficient Patient Identification for 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.^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^TM 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.

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

All of A2 Bio’s scientific posters and publications are available at www.a2bio.com/science/abstracts-and-publications/

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 (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 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 Escobar G, Berger TR, Maus MV. CAR-T cells in solid tumors: Challenges and breakthroughs. Cell Rep Med. 2025;102353.

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.

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The findings from EVEREST-2 include the first reported complete response in a patient with non-small cell lung cancer following treatment with a CAR T-cell therapy. This patient had progressive, metastatic NSCLC with KRAS G12V/STK11 co-mutations.