Abstract 2978: YH013, a novel EGFR x MET bispecific antibody-drug conjugate, exhibits potent antitumor efficacy

Abstract

Abstract Bispecific antibodies (BsAb) that target dual tumor-associated antigens have the advantages of invoking synergistic effects between two signaling pathways, increasing target tissue specificity, and reducing systemic toxicity. By combining the antibody-mediated specific targeting with potent killing from a cytotoxic payload, antibody-drug conjugates (ADC), and especially bispecific ADCs (BsADC), have become powerful therapeutic strategies. EGFR and MET are oncogenic proteins that are co-expressed in a wide range of tumors. Moreover, MET amplification is largely associated with drug resistance of EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) patients. Biocytogen developed a fully human EGFR x MET BsADC using our proprietary common light chain RenLiteTM mouse platform and knobs-into-holes technology. The BsAb showed enhanced internalization and binding affinity compared to parental monoclonal and monovalent antibodies in the EGFR/MET co-expressing NCI-H1975 cell line. After conjugating the BsAb with monomethyl auristatin E (MMAE) via a protease-cleavable linker, the resulting BsADC, YH013, exhibited a remarkable and dose-dependent anti-tumor efficacy in NCI-H1975 and NCI-H292 cell line-derived xenograft models. Moreover, in multiple patient-derived xenografts of NSCLC and pancreatic ductal adenocarcinoma (PDAC), which co-express EGFR and MET, YH013 demonstrated superior and durable efficacy that outperformed benchmark antibodies at a lower dose (3 mg/kg). Collectively, these results suggest that YH013 can be an effective treatment option for EGFR and MET co-expressing tumors and overcome MET-driven EGFR-TKI resistance to improve patient outcomes. Citation Format: Yanfei Han, Chengzhang Shang, Zhuon li, Zhenyan Han, Jun Li, Zixu Cui, Gao An, Wanjun Hao, Yujie Liu, Hao Li, Baihong Liu, Ellen Zhang, Qingcong Lin, Yi Yang, Yuelei Shen. YH013, a novel EGFR x MET bispecific antibody-drug conjugate, exhibits potent antitumor efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2978.