Abstract 6933: GQ1035: First-in-class ADC against novel targets for gastric cancer and ovarian cancer discovered via high-throughput screening

Abstract Background: Antibody-drug conjugates (ADCs) constitute a breakthrough in gastric cancer (GC) and ovarian cancer (OV) therapy; however about over 50% of patients remain ineligible for existing options, underscoring the urgent need for next-generation ADCs against novel targets. Among these, Target A has emerged as a promising candidate due to its high expression in GC and OV, with no significant correlation to CLDN18.2 or FRα—supporting its potential for ADC development. The iScreener™ platform's high-throughput conjugation capability, rooted in iLDC™/iGDC™ technologies, enables a screening-based strategy for the rapid identification of lead ADCs against Target A. Method/Results: To develop ADCs against Target A, we constructed a diverse library of ∼150 candidates on the iScreener™ platform by combining 11 antibodies with varied linker-payloads. The ADC library was screened using gastric cancer patient-derived organoid (PDO) models. In this screen, TopoIi-ADC and Exatecan-ADC demonstrated superior anti-tumor activity compared to other payload-based ADCs (e.g., DXd, MMAE, Eribulin). During in vivo screening, TopoIi-ADCs and Eribulin-ADCs emerged as the top candidates by demonstrating potent anti-tumor efficacy in a model resistant to a Topo1 inhibitor-based ADC. Through further refinement in PDX models, GQ1035 was selected based on its ability to induce significant tumor regression across models with varying target expression levels, while maintaining a good safety profile with no significant body weight loss. Safety study for lead candidate is currently ongoing in non-human primates (NHPs). Conclusion: GQ1035 shows a promising efficacy profile against gastric and ovarian cancers in preclinical PDO and PDX models. This positions GQ1035 as a potential breakthrough therapy in an area of high unmet medical need. It stands as a pioneering example of the strategic shift in biomedicine from “by design” to “by screening”. Citation Format: Shanshan Xie, Meijun Xiong, Lina Wang, Yajun Sun, Chong Liu, Zhongsheng Hu, Xinju Gao, Yanwen Feng, Yu Han, Zengyan Mu, Paul H. Song, Gang Qin, . GQ1035: First-in-class ADC against novel targets for gastric cancer and ovarian cancer discovered via high-throughput screening abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6933.