BigHat's AI-designed CDH17 antibody-drug conjugate BHB810 enters first-in-human trial for gastric cancer
核心洞察
BigHat Biosciences (搜索) has dosed the first patient in a Phase 1 trial of BHB810 (搜索), a CDH17 (搜索)-directed VHH-Fc antibody-drug conjugate for advanced gastric and GI cancers.
BHB810 (搜索) is the first clinical program to emerge from BigHat's AI-driven antibody design platform, marking a milestone in AI-generated therapeutic development.
Preclinical studies across nearly 30 tumor models showed complete or near-complete tumor clearance, including gastric cancers with low and heterogeneous CDH17 (搜索) expression.
BigHat Biosciences (搜索) has dosed its first patient with BHB810 (搜索), a cadherin-17 (CDH17 (搜索))-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 San Mateo, California-based company announced the milestone in its Phase 1, open-label, multicenter dose escalation and expansion study, which will initially enroll patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma.
The first-in-human trial will focus primarily on safety, tolerability, pharmacokinetics, and preliminary antitumor activity, with the trial anticipating enrollment of patients with broader advanced GI malignancies.
"The treatment of the first patient with BHB810 (搜索) marks an important step forward in our mission to enable transformative AI-designed therapeutics and comes during a period of steady momentum for BigHat, as we continue to advance both our pipeline of novel therapeutics and AI platform," said Peyton Greenside, co-founder and CEO of BigHat. "This is the first program we've taken from AI-generated design into human studies, validating the ability of our platform to identify and develop promising antibodies into clinic-ready therapeutics."
A Distinct Target in GI Cancers
BHB810 (搜索) uses a VHH-Fc antibody format — a compact nanobody-based scaffold — to deliver a cytotoxic payload to CDH17 (搜索)-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 target is notable for its differentiation from existing biomarker-driven approaches. The approved landscape now spans HER2 (搜索)-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 (搜索) targets CDH17 (搜索), a distinct antigen with no overlap with HER2, PD-L1 (搜索), or CLDN18.2 (搜索), which the company said could address patients ineligible for currently approved targeted therapies.
Preclinical Rationale
The preclinical rationale for BHB810 (搜索) 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 (搜索) expression. The company said the compact antibody format and stable payload technology produced a favorable preclinical safety profile.
The VHH-Fc format also differentiates BHB810 (搜索) 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.
Unmet Need and Clinical Context
"Despite recent advances, patients with advanced gastric cancers and other GI malignancies continue to face substantial unmet medical needs," said Principal Investigator Alexander Spira, M.D., Ph.D., Chief Executive Officer and Chief Scientific Officer of NEXT Oncology-Virginia and Co-Director of the Virginia Cancer Specialists Research Institute. "We are excited to help advance BHB810 (搜索), a potentially best-in-class CDH17 (搜索)-targeted antibody-drug conjugate developed using BigHat's AI-driven antibody engineering platform, as a potential new treatment option for patients."
Greenside added that BHB810 (搜索) "could offer a differentiated approach to address a target that has been difficult to drug well, and we are excited by the potential to offer a much-needed new treatment option for patients living with GI cancers."
Pipeline Momentum
The company has disclosed research collaborations with Merck, Johnson & Johnson, and Eli Lilly, but BHB810 (搜索) 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 (搜索) for solid tumors, is expected to enter the clinic in 2027.