- First‑in‑class DARKFOX‑targeting bispecific T cell engager: ENA101 is designed to selectively recognise the DARKFOX‑A3 peptide presented by HLA‑A*03:01, a highly prevalent HLA allele, enabling precise redirection of T cells to DARKFOX‑expressing tumour cells while sparing normal tissues.
- Potent and selective T cell–mediated anti‑tumor activity: ENA101 demonstrates robust T cell activation and tumour cell killing with low‑picomolar functional potency across multiple DARKFOX‑A3⁺ solid tumour models, with no activity observed in antigen‑negative controls.
- Compelling in vivo efficacy at low doses: In multiple xenograft models, once‑weekly dosing of ENA101 drove complete tumour regression across all dose levels tested, supporting strong translational potential.
- Drug-like properties supportive of clinical development: ENA101 exhibits high‑affinity binding to its target pHLA complex, favourable stability and manufacturability, and an extended plasma half‑life enabled by Enara’s proprietary EnTiCE® TCE platform.
- Broad clinical relevance of DARKFOX: Analyses demonstrate that DARKFOX is highly prevalent and homogeneously expressed across multiple high-unmet-need solid tumour indications, creating the opportunity for patient selection based on HLA‑A*03 positivity alone.
- Advancing into clinical development: ENA101 is advancing through IND-enabling studies with a clear development path to IND submission in 2H’2026.
ENA101 targets DARKFOX®, a novel, cancer‑specific Dark Antigen encoded by a previously undiscovered alternative open reading frame (alt‑ORF) within FOXM1. DARKFOX was discovered and validated using Enara’s proprietary EDAPT® platform and represents a new class of highly tumour-specific targets derived from the dark proteome.
“ENA101 exemplifies the power of uncovering antigens within the dark proteome to overcome long-standing challenges in solid tumour immunotherapy,” said Dr Joe Dukes, Chief Scientific Officer of Enara Bio. “The data presented today at AACR demonstrate that DARKFOX is a compelling cancer-specific target and that ENA101 exhibits the potency, specificity and druglike profile required to advance a best-in-class T cell engager toward the clinic.”
The oral presentation, titled “ENA101: A First‑in‑Class Bispecific T Cell Engager Targeting a DARKFOX Peptide Presented by Solid Tumours,” was delivered by Dr Joe Dukes in the Advances in Therapeutic Antibodies session.
(Abstract #4052). The presentation highlighted the discovery of DARKFOX, the engineering of ENA101, and the comprehensive preclinical dataset supporting its advancement into clinical development.
Enara Bio is currently advancing ENA101 through IND-enabling studies to support IND filing in 2H’2026.
The abstract is available in Proceedings of the American Association for Cancer Research Annual Meeting 2026.
ENA101 is a first‑in‑class bispecific T cell engager developed using Enara Bio’s proprietary EnTiCE platform. It incorporates a high‑affinity TCR‑mimic binder targeting the DARKFOX‑A3 peptide, a clinically validated anti‑CD3 arm, and an Fc‑based architecture for half‑life extension, to enable potent, selective and durable anti-tumour immune responses.
About Enara Bio
Enara Bio is shining a light on Dark Antigen® and T-cell biology to develop cancer immunotherapies designed to improve treatment outcomes for broad populations of cancer patients with solid tumours. Our pioneering EDAPT® platform enables us to discover cancer-specific antigens, including HLA-presented and cell surface antigens, from previously uncharted genomic ‘dark matter’. The result is a growing library of Dark Antigens that can address the need for novel, cancer-specific targets on solid tumours. Through our proprietary EnTiCE® platform, Enara is developing novel bispecific T cell engagers against Dark Antigen targets that are highly prevalent and homogenously expressed across solid tumours. Based in Oxford, UK, Enara Bio is backed by a strong syndicate of life science investors including RA Capital, Pfizer Ventures, M Ventures, Samsara BioCapital, SV Health Investors, and the Francis Crick Institute.
For more information, visit: www.enarabio.com.
Dark Antigen®, DARKFOX™, EDAPT® and EnTiCE® are trademarks of Enara Bio.
Contacts
Kevin Pojasek, President & CEO
info@enarabio.com
Stacey Davis, CBO & CFO
stacey.davis@enarabio.com
Frazer Hall, Mark Swallow
MEDiSTRAVA
enarabio@medistrava.com