BHB299

BHB299 is a first-in-class bispecific T-cell engager (TCE) targeting CEACAM6 and CD3, developed by BigHat Biosciences using their AI/ML-powered antibody design platform. The molecule features a "2+1" architecture, incorporating two VHH single-domain antibodies for CEACAM6 and a single CD3-binding domain. It is engineered for high-avidity binding to tumor cells with high CEACAM6 density while maintaining low affinity and fast dissociation from healthy myeloid cells, a mechanism designed to overcome the peripheral antigen sink and reduce on-target/off-tumor toxicities. Additionally, BHB299 includes a pH-conditional CD3 agonist to restrict T-cell activation to the acidic tumor microenvironment. Preclinical studies have demonstrated efficacy in models of colorectal, lung, and pancreatic cancers, with first-in-human trials planned for 2026.