The MET/HER3 antibody-drug conjugate with dual payload: A dual-target approach to eliminate tumor escape mechanism
Presenter: Ting-Yu Chang, PhD Session: Targeted Antigen Therapies and Immunity Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Yuan-Liang Wang , Chi-Huan Lu , Woan-Eng Chan , Ting-Yu Chang , Hong-Syuan Lin , Cheng-Yen Wei , Shin-Jin Lin , Lu-Tzu Lu , Meng-Hsin Liu , Wei-Jhen Huang , Ya-Chi Chen OBI Pharma, Inc, Taipei City, Taiwan
Abstract
Clinical evidence supports combination approaches such as EGFR plus MET TKIs, which achieve responses in MET-amplified resistance settings and demonstrate the critical role of MET signaling in acquired resistance. Meanwhile, HER3-directed ADCs have shown meaningful activity in refractory tumors, underscoring the therapeutic relevance of HER3 in resistant and heterogeneous cancer populations. Together, these findings highlight the rationale for co-targeting cMET and HER3, as simultaneous inhibition of these complementary pathways provides a strong foundation for the development of a bispecific ADC (BsADC) to overcome resistance and enhance antitumor efficacy. Our MET/HER3 bispecific ADC was constructed using the proprietary glycan-based site specific platform to simultaneously engage c-MET and HER3. The ADC carries two complementary cytotoxins— a microtubule inhibitor, MMAE and a topoisomerase I inhibitor derivative, exatecan, conjugated through the stable linker for controlled intracellular release and maximize antitumor activity. Blue native PAGE (BN-PAGE) and proximity ligation assay (PLA) data confirmed that simultaneous MET and HER3 engagement promote receptor clustering, enhancing internalization and intracellular payload delivery. In preclinical models, the bispecific dual-payload ADC induced stronger tumor regression than monospecific or parental ADCs. Broad activity was observed in c-MET/HER3 dual-positive non-small cell lung cancer and colorectal cancer models. This glycan-based site specific MET/HER3 bispecific dual-payload ADC warrants further clinical investigation as a promising therapeutic option for refractory tumors co-expressing cMET and HER3.
Disclosure
Y. Wang, None.. C. Lu, None.. W. Chan, None.. T. Chang, None.. H. Lin, None.. C. Wei, None.. S. Lin, None.. L. Lu, None.. M. Liu, None.. W. Huang, None.. Y. Chen, None.
Cited in
Control: 3615 · Presentation Id: 4051 · Meeting 21436