EMB-01, a Tetravalent Bispecific Antibody, Inducing Co-Degradation of EGFR and c-Met for Enhanced Anti-Tumor Efficacy.

The bispecific antibody EMB-01 (bafisontamab), constructed using EpimAb's proprietary FIT-Ig platform, is designed to simultaneously target epidermal growth factor receptor (EGFR) and receptor tyrosine kinase Met (c-Met). Here, we characterize EMB-01's binding properties, mechanisms of action, and anti-tumor efficacy using in vitro cell line models and in vivo models (patient-derived xenografts, PDXs). EMB-01 exhibits high-affinity binding to EGFR and c-Met, induces co-degradation of both receptors, enhances endocytosis, and elicits strong antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) effects. Mechanistically, EMB-01 effectively inhibits ligand-induced receptor phosphorylation, downstream AKT activation, and IL-8 secretion. Furthermore, EMB-01 demonstrates potent anti-tumor activity across multiple tumor models, outperforming existing EGFR-targeted therapies and other bispecific antibodies, while maintaining favorable pharmacokinetics with good tolerability in cynomolgus monkeys. These findings support the clinical development of EMB-01 as a promising therapeutic for EGFR/c-Met-driven cancers.