Abstract 2118: ABN501: A CLDN3-targeted monoclonal antibody with proven safety, pharmacokinetics, and synergistic anti-tumor efficacy

Abstract ABN501 is an afucosylated monoclonal antibody specifically designed to target claudin-3 (CLDN3), a protein frequently overexpressed in various solid tumors, including small-cell lung cancer (SCLC). Given the critical role of CLDN3 in cancer cell proliferation and tumorigenesis, it is recognized as a promising therapeutic target. In this study, we evaluated the preclinical safety and efficacy of ABN501, focusing on its potential for clinical development as a targeted cancer therapy. To identify suitable animal models for toxicity assessment, we investigated the cross-species reactivity of ABN501 with CLDN3. Our results confirmed that ABN501 binds to CLDN3 across human, mouse, rat, and cynomolgus monkey species. Based on these findings, rats and cynomolgus monkeys were selected for comprehensive toxicity evaluations, including single-dose and repeated-dose studies. Notably, even at the highest administered doses, ABN501 exhibited no significant changes in key toxicity markers, demonstrating its exceptional safety profile. We further assessed the therapeutic potential of ABN501 as both monotherapy and in combination with chemotherapy. Chemotherapy was shown to upregulate CLDN3 expression in lung cancer cell lines, thereby enhancing the antitumor activity of ABN501 and confirming a synergistic effect. In conclusion, our preclinical studies demonstrate that ABN501 is a safe and effective CLDN3-targeting monoclonal antibody for treating CLDN3-overexpressing cancers. Its excellent safety profile and synergistic effects in combination with chemotherapy present a promising strategy for improving treatment outcomes, particularly in cancers with limited targeted treatment options. These findings pave the way for further clinical investigation, particularly in lung cancer and other CLDN3-expressing malignancies. Citation Format: Saehyung Lee, Jae Choi, Sunghyun Hong, Ha Yeon Park, Ho Jin Lee, Jaemun Kim, Sangin Lee, Seung Hwa Jung, Myeung Ryun Seo, Hobin Yang, Sungyoul Hong, Jun Young Choi, Na Young Kim, Young Kee Shin. ABN501: A CLDN3-targeted monoclonal antibody with proven safety, pharmacokinetics, and synergistic anti-tumor efficacy [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 2118.