CHICAGO, Illinois, 21 May 2026
A2 Biotherapeutics, Inc. announced new safety and efficacy results from its ongoing EVEREST-2 Phase 1/2 clinical study, including an update on what the company describes as the first reported complete response (CR) to CAR T-cell therapy in a patient with non-small cell lung cancer (NSCLC). The findings will be presented during poster sessions at the ASCO Annual Meeting 2026 in Chicago. The results highlight the growing potential of A2 Bio’s proprietary Tmod™ logic-gated cell therapy platform to address one of the biggest challenges in solid tumor treatment — distinguishing cancer cells from healthy tissue while maintaining strong anti-tumor activity.
EVEREST-2 Shows Encouraging Safety and Tumor Response Data
The EVEREST-2 study is evaluating A2B694, a mesothelin-targeted logic-gated CAR T-cell therapy designed for patients with advanced solid tumors that have lost HLA-A*02 expression. As of January 5, 2026, the Phase 1 portion enrolled 13 patients across multiple cancer types including ovarian cancer, pancreatic cancer, colorectal cancer, mesothelioma, gastroesophageal cancer, and NSCLC.
The most notable result came from a patient with heavily pretreated KRAS G12V/STK11 co-mutated NSCLC, a subtype associated with poor prognosis and resistance to standard chemoimmunotherapy. Following treatment with A2B694, the patient achieved a complete response at day 90, which was later confirmed through independent central review at day 180. PET-CT imaging at day 190 showed no evidence of disease.
Although the patient later experienced an isolated central nervous system relapse, non-CNS complete response remained ongoing at day 284, and follow-up imaging at 15 months continued to show no new extracranial disease progression. Investigators also confirmed long-term persistence of A2B694 cells in the bloodstream.
Logic-Gated CAR-T Platform Targets Solid Tumor Challenges
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CAR T-cell therapies have historically shown strong success in blood cancers but limited activity in solid tumors due to toxicity and tumor-targeting challenges. A2 Bio’s Tmod™ platform was specifically designed to overcome these limitations using a dual-receptor “logic-gate” system that selectively attacks tumor cells while sparing normal tissues.
The therapy combines an activator receptor targeting mesothelin (MSLN) with a blocker receptor recognizing HLA-A*02, which is absent in tumor cells but present in healthy tissue. This approach aims to improve precision targeting and reduce off-target toxicity.
Safety findings from EVEREST-2 were encouraging overall. No dose-limiting toxicities or new safety signals were observed after up to 17 months of follow-up. One patient experienced grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), while another developed grade 1 cytokine release syndrome (CRS). No deaths were linked to A2B694, and no patients discontinued treatment due to adverse events.
A2 Bio Advances Next-Generation Armored CAR-T Therapy
A2 Bio also provided updates on A2B543, an enhanced version of A2B694 that incorporates a membrane-tethered IL-12 booster designed to improve CAR T-cell potency and persistence while minimizing systemic IL-12 toxicity. The first patient receiving A2B543 was enrolled in January 2026, and dose escalation is ongoing.
The company believes the addition of inducible membrane-bound IL-12 could significantly strengthen anti-tumor immune responses without compromising the selective targeting capabilities of the Tmod™ platform. Additional ASCO presentations will further explore how IL-12 and related immune-boosting technologies may improve the effectiveness of precision cell therapies in solid tumors.
The EVEREST-2 study continues recruiting patients with mesothelin-expressing solid tumors, including NSCLC, pancreatic cancer, ovarian cancer, mesothelioma, and colorectal cancer.
Source: A2 Biotherapeutics press release
