Abstract 2940: Preclinical development of a next generation antibody drug conjugate (ADC) targeting CDH17 for treatment of solid tumors

Abstract Cadherin-17 (CDH17) is a membranous cell adhesion protein predominantly expressed in intestinal epithelial cells. High CDH17 expression is associated with metastatic progression in different cancers that mainly originate from gastrointestinal tracts. YL217 is a novel CDH17 -targeting antibody-drug conjugate (ADC) and built on MediLink’s TMALIN® platform, which can release the payload both in the tumor cell and in the tumor microenvironment. This study evaluated efficacy, safety and pharmacokinetic profiles of YL217 in non-clinical studies. YL217 could specifically bind to CDH17 on tumor cell surfaces, followed with payload release both in the lysosome through internalization and in the tumor microenvironment. These translate in vivo where YL217 showed superior efficacy in causing tumor regressions and good tolerability in both cell lines and patient-derived xenograft (CDX and PDX) mouse models with low to high CDH17 expression levels. The in vivo pharmacokinetics in monkeys showed that YL217 is highly stable with less than 0.1% (molar ratio) payload released in circulation. These non-clinical data suggest the high stability of the linker in circulation as well as efficient payload release in tumors. Moreover, acceptable safety profiles were also noted in monkey GLP toxicity studies. Taken together, preclinical data suggest that YL217 could be further developed in the treatment of CDH17-positive cancer patients. Citation Format: Wei Lian, Qing Zong, Chun Deng, Peng Zou, Liang Xiao, Tongtong Xue, Jiaqiang Cai. Preclinical development of a next generation antibody drug conjugate (ADC) targeting CDH17 for treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2940.