Abstract 6851: An integrated preclinical platform for antibody-drug conjugate development

Abstract Antibody-drug conjugates (ADCs) are an innovative class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potent cytotoxic effects of small-molecule drugs. The development of ADCs requires an integrated approach to identify targets, optimize payload delivery, and validate efficacy across ex vivo and in vivo preclinical models. Selecting the right pipeline supporting ADC development is essential. Cell lines often fail to express the specific target antigens leading to discarding or retaining the wrong targets causing clinical failure. For these reasons, ADC development needs clinically relevant models such as patient-derived xenograft (PDX) reflecting clinical trial populations. Champions Oncology has generated a comprehensive preclinical platform to support ADC development by integrating molecular profiling, multi-omics integration and histology data along with functional assays and patient-derived ex-vivo and in vivo models. Champions’ PDX bank includes over 1500 models, extensively characterized at a molecular level, and highly reflective of the current clinical trial populations. The deep multi-omics characterization, which includes a proteomic dataset in addition to transcriptomics data, provides a unique advantage in model selection for ADC development. The platform identifies novel targets by analyzing and correlating gene and protein expression in PDX models and validating these findings in clinical tumor samples and normal tissue. This ensures that potential ADC targets exhibit limited overlap with known ADC targets and are differentially expressed in tumor tissues compared to normal tissues, thereby minimizing off-target toxicity. Following target identification, the platform includes steps enabling the discovery and development phase, leveraging Champions’ cell-based assays, proprietary ex vivo TumorGraft3D organoid platform, and in vivo model. These models, derived from primary patient tumors, retain the molecular and histopathological characteristics of human cancers enabling a deeper understanding of target biology, ADC internalization, and downstream cytotoxic effects. These analyses are integrated into the workflow to inform ADC construct design, including optimizing antibody specificity, and payload potency. Here we show an example of how Champions Oncology’s integrated preclinical ADC development pipeline offers a comprehensive approach for identifying and validating new targets during ADC optimization for therapeutic success. This platform accelerates ADC discovery while ensuring translational relevance, paving the way for next-generation cancer therapeutics. Citation Format: Stefano Cairo, Mara Gilardi, Marianna Zipeto, Michael Ritchie. An integrated preclinical platform for antibody-drug conjugate development [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 6851.