Development

BigHat's AI-designed CDH17 antibody enters human testing for gastric cancer

BigHat's AI-designed CDH17 antibody enters human testing for gastric cancer

San Mateo, California-based BigHat Biosciences has dosed its first patient with BHB810, a cadherin-17 (CDH17)-directed antibody-drug conjugate (ADC) for advanced gastric and gastrointestinal (GI) cancers — marking the first human study to emerge from the company's AI-driven antibody design platform.

The Phase I, open-label, multicenter dose escalation and expansion study will initially enroll patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma, with a primary focus on safety, tolerability, pharmacokinetics, and preliminary antitumor activity. The trial anticipates enrolling patients with broader advanced GI malignancies.

BHB810 uses a VHH-Fc antibody format — a compact nanobody-based scaffold — to deliver a cytotoxic payload to CDH17-expressing tumor cells. CDH17 is a cell-surface adhesion molecule expressed across a broad range of GI cancers, including gastric, colorectal, and pancreatic tumors. No CDH17-directed therapy is currently approved.

The preclinical rationale is notable for its breadth: BigHat reports complete or near-complete tumor clearance across nearly 30 patient- and cell-derived tumor models, including gastric cancers with low and heterogeneous CDH17 expression. The company said the compact antibody format and stable payload technology produced a favorable preclinical safety profile.

The AllSci BriefSystematic R&D and deal news. Daily.

The approved landscape now spans HER2-directed agents including AstraZeneca and Daiichi Sankyo's Enhertu (fam-trastuzumab deruxtecan), checkpoint inhibitors such as Merck's Keytruda (pembrolizumab) and Bristol Myers Squibb's Opdivo (nivolumab), and Astellas' Vyloy (zolbetuximab-clzb) targeting Claudin 18.2. Each of these requires a specific biomarker. BHB810 targets CDH17, a distinct antigen with no overlap with HER2, PD-L1, or CLDN18.2, which the company said could address patients ineligible for currently approved targeted therapies.

The VHH-Fc format also differentiates BHB810 structurally from conventional IgG-based ADCs such as fam-trastuzumab deruxtecan. BigHat asserts the smaller antibody scaffold may offer improved tumor penetration and manufacturability, though these claims have not yet been tested clinically.

The company has disclosed research collaborations with Merck, Johnson & Johnson, and Eli Lilly, but BHB810 is the first clinical program from its AI discovery platform to reach human studies. A second pipeline asset, BHB299, an avidity-driven T-cell engager targeting CEACAM6 for solid tumors, is expected to enter the clinic in 2027.


Spot something wrong? Report an issue with this article