A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage immunotherapy company developing first-in-class logic-gated therapies for solid tumors, today announced early safety and efficacy data from the ongoing DENALI-1 clinical study (NCT06682793). The study evaluates A2B395, an allogeneic, logic-gated chimeric antigen receptor T-cell (CAR T-cell) therapy targeting EGFR, developed based on the company’s proprietary TmodTM platform. The findings include the first reported complete response (CR) 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) following treatment with A2B395. This data is being presented in a poster presentation during the 2026 Cell Coast Conference taking place October 9 – 11, 2026, in Tampa, Florida.

DENALI-1 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.

Few treatment advancements have been made for anal cancer. Standard EGFR-targeted therapies can cause severe toxicities,1 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.2 According to the latest GLOBOCAN estimates (2020), HNSCC accounts for an estimated 890,000 new cases, or approximately 4.5% of all cancer diagnoses around the world, and 450,000 deaths per year, or approximately 4.6% of global cancer deaths.3

Complete responses have rarely been observed in studies of CAR T-cell therapies for the treatment of solid tumors, and to date none has been reported in patients with anal cancer.4

“We are deeply encouraged by the DENALI-1 study data being presented during the Cell Coast Conference, notably the first reported complete response in a patient with anal squamous cell carcinoma treated at our institution. This patient had previously undergone multiple lines of chemotherapy, retifanlimab, and radiation, before receiving A2B395, an allogeneic CAR T-cell therapy built on the Tmod platform, and experienced minimal toxicity. These early findings support the potential for A2B395 to treat patients with solid tumors expressing EGFR,” said Kedar Kirtane, M.D., Medical Director for Solid Tumor Cellular Therapy at Moffitt Cancer Center and the principal investigator who oversaw the treatment of the patient.

“Our head and neck cancer patient had previously received several lines of therapy for a painful, softball-size tumor in their neck and had no response to any of those other treatments. After receiving A2B395, pain from the tumor resolved and the tumor shrank enough to allow them to return to work, and it is the first time since diagnosis to not be receiving regular chemotherapy doses. 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.

“Recent results from our DENALI-1 and EVEREST-2 (NCT06051695) clinical trials provide exciting early evidence of safety and efficacy. Following a single dose of A2B395, we saw heavily pre-treated patients with refractory anal cancer and head and neck cancer respectively achieve a complete response and a partial response. Importantly, both patients experienced no serious adverse events. We previously reported similar outcomes with the 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 encouraging early proof-of-concept that our Tmod logic-gated CAR T platform – both autologous and allogeneic approaches – can safely treat difficult solid tumors,” said John Welch, M.D., Ph.D., Chief Medical Officer, A2 Bio.

Summary of DENALI-1 Study Findings

As of August 1, 2026, 10 patients received A2B395 for advanced solid tumors: anal (n=1); head and neck squamous cell (HNSCC; n=1); non-small cell lung (n=2); colorectal (n=3); and breast (n=3). The median patient age is 56 (range 33-70) years, and 80 percent enrolled are women. Dose levels (DLs) were 2×108 (n=3), 4×108 (n=4), and 8×108 (n=3) cells.

  • Safety: Lymphodepletion was well-tolerated with anticipated, transient cytopenias. No graft-versus-host disease, immune effector cell-associated neurotoxicity syndrome (ICANS), dose-limiting toxicities (DLTs), immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, or fatal adverse events were reported. Two patients had grade 1/2 cytokine release syndrome that fully resolved.

  • Efficacy: Nine patients were evaluable for efficacy. The patient with unresectable anal cancer, after five different chemotherapy regimens and two rounds of radiation treatment, received A2B395 (DL3) and achieved a complete response (CR) on Day 28, with complete resolution of all target and non-target lesions and no serious adverse events.

  • The patient with HNSCC (DL2) achieved a confirmed partial response (PR) on Day 180, after a 37% reduction in 3 target lesions, the largest which was 7.7 cm prior to receiving A2B395.

  • Remaining best responses were stable disease (n=5) and progressive disease (n=2), resulting in a 78% disease control rate.

  • Translational: A2B395 was detectable in blood and biopsies across all dose levels.

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, in adults. 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 patients with recurrent unresectable, locally advanced, or metastatic colorectal, non-small cell lung, triple-negative breast, head and neck squamous cell, and renal cell cancer, cholangiocarcinoma, and cancer of unknown primary 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.

More information about DENALI-1 and clinical trial sites participating in the study are available on the A2 Bio clinical trials website.

About the Tmod™ Platform

Invented at A2 Bio, the TmodTM platform is a precision-targeting cellular system, designed with logic-gate technology to enable immune cells to unequivocally differentiate tumors from normal tissues. The system consists of activator and blocker receptors. The activator recognizes antigens on tumor cells and triggers their destruction, while the blocker recognizes antigens on normal cells and protects them. This novel blocker technology enables precise, personalized, and effective T-cell targeting specifically against tumors.

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

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, visit the company’s website at www.a2bio.com.

References

1 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.

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

3 Barsouk A, et al. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med Sci (Basel). 2023;11:42. doi: 10.3390/medsci11020042.

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

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