A2 Biotherapeutics Presents Updated Safety and Efficacy Data from EVEREST-2 and DENALI-1 Clinical Studies during 2026 Annual Meeting of the Society for Immunotherapy of Cancer

EVEREST-2 findings include update on first complete response to CAR T-cell therapy in patient with non-small cell lung cancer, ongoing after 12 months follow-up

DENALI-1 findings include update on first reported case of complete response to CAR T-cell therapy in patient with metastatic anal cancer, and partial response in a patient with refractory head and neck squamous cell cancer

PHOENIX--(BUSINESS WIRE)--A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage immunotherapy company developing first-in-class logic-gated cell therapies for solid tumors, today announced the presentation of updated safety and efficacy data from the EVEREST-2 (NCT06051695) and DENALI-1 (NCT06682793) clinical studies. The data includes updates on the first reported case of complete response (CR) to CAR T-cell therapy in a patient with non-small cell lung cancer (NSCLC) in the EVEREST-2 study, as well as the first reported case of complete response in a patient with metastatic anal cancer and a partial response with disease control for six months in a patient with refractory head and neck squamous cell cancer (HNSCC) from the DENALI-1 study. The results are being presented at the 41st Annual Meeting of the Society for Immunotherapy of Cancer (SITC) taking place November 4–8, 2026, in Phoenix. The EVEREST-2 abstract (#559) was recognized as a Top 150 Abstract.

Complete responses have rarely been observed in studies of CAR T-cell therapies for the treatment of solid tumors, and none has been reported in patients with lung cancer.¹

“Our NSCLC patient achieved a systemic complete response that remains ongoing after more than 12 months of follow-up. These findings from the EVEREST-2 study support the potential of precision cell therapy targeting mesothelin-expressing solid tumors, such as NSCLC, mesothelioma, pancreatic, ovarian, and colorectal cancer,” said Salman R. Punekar, M.D., Medical Director of Solid Tumor Cell Therapy, NYU Langone Health, Perlmutter Cancer Center.

EVEREST-2 (NCT06051695) is first-in-human, open-label, Phase 1/2 study evaluating the safety and efficacy of A2B694 (Arm 1) and A2B543 (Arm 2). A2B694 is an autologous, logic-gated, Tmod™ CAR T-cell therapy combining a mesothelin (MSLN) CAR T activator with an HLA-A*02 blocker to enhance tumor selectivity. A2B543 uses the same Tmod™ construct with an NFAT-driven, membrane-tethered IL-12 (mem-IL-12) booster designed to enhance Tmod™ potency and persistence while limiting systemic IL-12 exposure.

Few treatment advancements have been made for anal cancer. Standard EGFR-targeted therapies can cause severe toxicities,² and surgical treatments can impact a patient’s quality of life.

Head and neck cancers are the seventh most common cancer worldwide, and high rates of morbidity and mortality are associated with this disease.³

“Our head and neck cancer patient treated in DENALI-1 had previously received several lines of therapy for a painful, softball-size tumor in their neck and had no response to those other treatments. After receiving A2B395, pain from the tumor resolved and the tumor shrank enough to allow them to return to work, making it the first time since diagnosis that the patient has not required regular chemotherapy. The partial response and minimal toxicity from the treatment resulted in a profound improvement of the patient’s quality of life,” said Matthew Ulrickson, M.D., Chief, Section of Hematology, Banner MD Anderson Cancer Center.

DENALI-1 (NCT06682793) is a first-in-human, open-label, Phase 1/2 study evaluating the safety and recommended Phase 2 dose of A2B395 in adults with previously treated EGFR-positive advanced solid tumors. DENALI-1 is currently enrolling patients with recurrent unresectable, locally advanced, or metastatic solid tumors associated with EGFR expression. A2B395 represents the first non–HLA-matched allogeneic CAR T-cell therapy with an unmodified, unselected T-cell receptor (TCR) and a blocker designed to mitigate graft-versus-host disease (GVHD) risk.

“We are encouraged by the results from our ongoing DENALI-1 and EVEREST-2 studies, which continue to build clinical evidence of safety and efficacy of our investigational Tmod™-based CAR T-cell therapies. Following a single dose of A2B395, heavily pre-treated patients with refractory anal cancer and head and neck cancer achieved a complete response and a partial response, respectively. We are also encouraged by the findings for our MSLN-targeted autologous CAR T-cell therapy A2B694, including a complete response by central review in a patient with refractory lung cancer. Together, these results provide early proof-of-concept that our Tmod™-based CAR T-cell therapies – both autologous and allogeneic approaches – can safely treat patients with complex, advanced solid tumors,” said John Welch, M.D., Ph.D., chief medical officer, A2 Bio.

The study abstracts are available online on the SITC website.

EVEREST-2: Study Findings

As of September 1, 2026, 16 patients were enrolled in EVEREST-2. Three patients were enrolled in Arm 2, receiving A2B543, the IL-12 boosted Tmod™ CAR T-cell therapy, at dose level 1 (4 × 10⁸ cells). All three patients were women (ages 45, 45, and 51 years) with pancreatic cancer. 13 patients were enrolled in Arm 1, receiving A2B694 (without the IL-12 booster) across 4 dose levels (1–6 × 10⁸ cells). Median age was 59 years. Tumor types included colorectal cancer (n=4), pancreatic cancer (n=3), ovarian cancer (n=3), non–small cell lung cancer (n=1), gastroesophageal cancer (n=1), and mesothelioma (n=1).

• A2B543 and A2B694 demonstrated manageable safety and tolerability in all 16 patients. The safety findings to date are consistent with the intended logic-gated design, with no dose-limiting toxicities (DLTs) or grade 4 Tmod™ CAR T cell–related AEs reported. In Arm 2 (A2B543), there was one case of grade 1 cytokine release syndrome (CRS). In Arm 1 (A2B694), there was one case each of grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), grade 1 ICANS and grade 1 CRS.
• In Arm 2, the two evaluable pancreatic cancer patients at dose level 1 had best overall responses of stable disease (SD). In Arm 1, among 13 evaluable patients, the best responses were CR (n=1; non–small cell lung cancer), SD (n=8), and progressive disease (PD) (n=4). The CR was confirmed at Day 90 by central review per RECIST 1.1 and remains ongoing after more than 12 months of follow-up.
• A2B543 was associated with higher Tmod™ expansion than most A2B694-treated patients. Serum IL-12 remained in normal range <5 pg/mL through Day 56 in both patients treated with A2B543.
• The maximum tolerated dose has not been reached.

DENALI-1: Study Findings

As of August 21, 2026, 11 patients received A2B395 in DENALI-1. Tumor types included anal cancer (n=1), head and neck cancer (n=1), non–small cell lung cancer (n=2), colorectal cancer (n=4), and breast cancer (n=3). The median age was 56 years (range, 33–70), and 80% of patients were women.

• A2B395 was well tolerated with no DLTs, GVHD, or immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). One patient experienced grade 1 CRS and one experienced grade 2; both fully resolved. On-target, off-tumor toxicities were manageable and consistent with the intended tumor-selective design of logic-gated Tmod™.
• Antitumor activity was observed with A2B395. One patient with unresectable anal cancer after five prior chemotherapy regimens and two courses of radiation therapy, received A2B395 at DL3 and achieved a CR on Day 28, with resolution of all target and non-target lesions and no serious adverse events.
• One patient with refractory head and neck cancer after multiple prior therapies received A2B395 at DL2 and achieved a PR on Day 180, with ongoing disease control at 6 months.
• Among nine efficacy-evaluable patients, best responses were CR (n=1), PR (n=1), SD (n=5), and PD (n=2), for a disease control rate of 78%.
• A2B395 was detected in peripheral blood and biopsies in all treated patients.
• The maximum tolerated dose has not been reached.

Poster Presentation Details

Abstract Title	Presenting Author	Abstract Number	Poster Presentation Date	Location
Non-gene edited, allogeneic, EGFR-targeted CAR T using a logic-gate to prevent on-target, off-tumor toxicity and mitigate GVHD: initial data from the DENALI-1 study of A2B395 in advanced solid tumors	Matthew Ulrickson, M.D., Banner MD Anderson Cancer Center	527	Friday, Nov. 6 12:15 – 1:45 pm MT 5:30 – 7:00pm MT	PCC-North Building- Lower Level- Exhibition Halls 4-5-6
Armoring logic-gated CAR T cells with a membrane-tethered IL-12 booster: initial data from the EVEREST-2 study of A2B543 in advanced solid tumors	Salman Punekar, M.D., New York University Langone Health, Perlmutter Cancer Center	559

About EVEREST-2

The EVEREST-2 master protocol (NCT06051695) is a seamless Phase 1/2 study evaluating the safety and efficacy of A2B694 (Arm 1) and A2B543 (Arm 2), autologous logic-gated investigational cell therapies 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 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. A2B543 contains the same Tmod™ construct as A2B694 with an added mem-IL-12 booster. The EVEREST-2 study is enrolling adults 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. Patients are enrolled 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.

About DENALI-1

DENALI-1 (NCT06682793) is a phase 1/2, multicenter, open-label, nonrandomized study evaluating the safety and efficacy of A2B395, an allogeneic logic-gated Tmod™ CAR T-cell therapy. Patients are enrolled 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 DENALI-1. A2B395 uses a Tmod™ logic-gate: an activator targeting EGFR and a blocker targeting HLA-A*02. In patients with HLA-A*02 loss of heterozygosity (LOH), the blocker inhibits both CAR and endogenous T-cell receptor (TCR) activity on normal tissue, providing tumor selectivity without gene editing, reducing on-target, off-tumor toxicity, and mitigating graft-versus-host disease. DENALI-1 is currently enrolling adults with recurrent unresectable, locally advanced, or metastatic colorectal, non-small cell lung, triple-negative breast, head and neck squamous cell, and renal cell cancer, or other solid tumors associated with EGFR expression. Patients are not required to undergo leukapheresis to receive treatment on DENALI-1 because A2B395 is an allogeneic treatment.

About BASECAMP-1

BASECAMP-1 (NCT04981119) is a prescreening study to identify patients for potential treatment in A2 Bio 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 heterozygosity in the tumor, the biomarker of interest for the A2 Bio studies. Patients eligible for autologous therapy 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 cancer, pancreatic cancer, ovarian cancer, colorectal cancer, mesothelioma, head and neck squamous cell carcinoma, triple-negative breast cancer, renal cell carcinoma, and other solid tumors.

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, et al. CAR-T cells in solid tumors: Challenges and breakthroughs. Cell Reports Medicine. 2025;6;102353. doi: j.xcrm.2025.102353.

² Macdonald JB, et al. Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane. J Am Acad Dermatol. 2015;72:203-218. doi: 10.1016/j.jaad.2014.07.032.

³ Kirtane K, et al. Am Soc Clin Oncol Educ Book 46. 2026;e516922. doi: 10.1200/EDBK-26-516922.