Abstract 3185: SCR-A019, a first-in-class biparatopic ADC targeting MSLN, with a novel topoisomerase I inhibitor demonstrates encouraging efficacy in preclinical models

Abstract Background: Mesothelin (MSLN) is a GPI-anchored glycoprotein that is expressed on many cancers but limited in normal tissues, which makes it an attractive target for antibody-based cancer therapy. However, MSLN is shed from surface of cells at high levels via proteases that cleave at its membrane-proximal C-terminal region. Shed MSLN accumulates in patient fluids and tumors and can block anti-MSLN antibodies from killing cancer cells. To overcome the challenge of MSLN shedding, we developed a novel biparatopic ADC which prefers binding to membrane MSLN rather than soluble MSLN. Method Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3185.