YH013 is a bispecific antibody-drug conjugate (ADC) designed to treat solid tumors by targeting both EGFR and MET receptors. The bispecific antibody was assembled using common light chain antibodies produced by RenLite, a fully human antibody mouse. Its monoclonal antibody structure facilitates easy purification and drug conjugation. YH013 is currently in the CMC stage of development.
Preclinical studies have demonstrated the following findings:
1. EGFR x MET bispecific antibody (YH013 unconjugated, YH013 unconj. for short) showed higher binding ability than parental monoclonal and monovalent antibodies in antigen double-positive NCI-H1975 (EGFR+ MET+) cancer cells.
2. YH013 unconj. has superior endocytosis activity over parental monoclonal and monovalent antibodies in antigen double-positive NCI-H1975 cancer cells.
Figure 2. Tumor cell endocytosis
3. YH013 showed outstanding tumor inhibition in CDX and PDX models.
Figure 3. YH013 induced dose-dependent tumor inhibition in NSCLC CDX（B-NDG + NCI-H1975）and showed robust anti-tumor effect in pancreatic PDX（B-NDG + BP209）model.
4. YH013 demonstrated CMC-suitable physiochemical properties.
EGFR (epidermal growth factor receptor) is a transmembrane protein with cytoplasmic kinase activity that transduces important growth factor signaling from the extracellular milieu to the cell.
MET (mesenchymal-epithelial transition factor) gene amplification constitutes the most frequent cause of bypass signaling activation as an acquired resistance mechanism to EGFR TKIs.
EGFR and MET co-express on many tumor types.
In 2021, Amivantamab (EGFR x MET bispecific antibody) was approved by FDA.
AACR 2023: YH013, a Novel Bispecific EGFR x MET Antibody-Drug Conjugate, Exhibits Potent Anti-Tumor Efficacy