OXFORD, UK, April 20, 2026

Enara Bio announced the presentation of breakthrough preclinical data for ENA101, its first-in-class bispecific T cell engager (TCE) targeting the novel DARKFOX antigen, at the AACR Annual Meeting 2026. The findings highlight ENA101’s potent and selective anti-tumor activity across multiple solid tumor models, positioning the therapy as a promising next-generation immunotherapy designed to overcome long-standing challenges in treating solid tumors.

First-in-Class DARKFOX Targeting Opens New Immunotherapy Pathways

ENA101 represents a pioneering approach in cancer immunotherapy, leveraging Enara Bio’s proprietary discovery platforms to target DARKFOX®, a cancer-specific antigen derived from the “dark proteome”—a previously unexplored region of the genome. This innovative target is encoded by an alternative open reading frame (alt-ORF) within FOXM1, enabling high tumor specificity while sparing healthy tissues.

The therapy is engineered to recognize the DARKFOX-A3 peptide presented by the HLA-A*03:01 allele, one of the most prevalent HLA types globally, allowing for broad patient applicability with precise immune targeting. By redirecting T cells specifically toward cancer cells expressing DARKFOX, ENA101 offers a highly selective mechanism of action, addressing a major limitation of conventional immunotherapies that often lack tumor specificity and can lead to off-target effects.

Robust Preclinical Efficacy and Strong Safety Profile

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Preclinical data presented at AACR demonstrated that ENA101 delivers exceptional T cell–mediated tumor killing with low-picomolar potency, indicating high therapeutic efficiency even at minimal concentrations. Across multiple DARKFOX-A3–positive solid tumor models, the therapy showed robust T cell activation and complete tumor cell eradication, while importantly no activity was observed in antigen-negative controls, confirming its precision targeting capability.

In vivo studies further reinforced its potential, with once-weekly dosing leading to complete tumor regression across all tested dose levels in xenograft models. These findings suggest a strong translational potential for clinical success, particularly in difficult-to-treat solid tumors. Additionally, ENA101 demonstrated favorable drug-like properties, including high-affinity binding, stability, manufacturability, and extended plasma half-life, enabled by Enara’s proprietary EnTiCE® platform, supporting its advancement into human trials.

Broad Clinical Potential and Path to IND Submission

The research also highlighted the broad clinical relevance of the DARKFOX target, which is highly prevalent and consistently expressed across multiple solid tumor types, offering opportunities for patient selection based primarily on HLA-A*03 positivity. This simplifies patient stratification and could accelerate clinical adoption compared to more complex biomarker-driven approaches.

ENA101 is currently progressing through IND-enabling studies, with a clear regulatory pathway toward Investigational New Drug (IND) submission expected in the second half of 2026. The therapy’s design integrates a TCR-mimic binder, anti-CD3 targeting arm, and Fc-based architecture, enabling durable immune responses and improved pharmacokinetics, key factors for clinical success.

The development of ENA101 underscores a significant advancement in immuno-oncology, particularly in expanding the scope of T cell engager therapies into solid tumors, an area historically dominated by challenges such as limited target specificity and tumor heterogeneity. By unlocking targets within the dark proteome, Enara Bio is pioneering a new class of cancer-specific antigens, opening the door to more precise, effective, and scalable immunotherapies. As the program advances toward clinical trials, ENA101 is positioned to reshape treatment paradigms for solid tumors, offering new hope for patients with limited therapeutic options and reinforcing the growing role of innovative biologics in precision oncology

Source: Enara Bio press release