Abstract B136: Degrader-Antibody Conjugate Platform: Experimental Capabilities in Characterization and Evaluation – Fom <i>In Vitro</i> Assays to <i>In Vivo</i> Studies

Abstract Background: Degrader-antibody conjugates (DACs) typically consist of a tumor-targeting antibody and a conjugated degrader payload, linked via a chemical linker. By integrating the degrader payload’s capacity to precisely degrade disease-causing proteins with the antibody’s tumor-targeting specificity, DACs emerge as an innovative and promising therapeutic modality for cancer treatment. Herein, we present the well-established DAC integrated platform developed by ICE Bioscience, which facilitates the characterization and evaluation of DACs from in vitro assays to in vivo models. Method: ICE has adopted diverse molecular-based, cell-based, and in vivo mouse model-based strategies to evaluate degrader payloads, antibodies, and DACs. Specifically, for detecting target binding and degradation events, ICE provides ready-to-use spectral shift and HTRF assays to measure binary/ternary complex formation; HiBiT, flow cytometry (FC) and WB assays are applied to quantify target and off-target degradation. For DAC characterization, ICE has established ligand binding assays (e.g., ELISA) and LC-MS approaches to analyze pharmacokinetics (PK) and drug-antibody ratios (DAR). Additionally, flow cytometry (FC) is used to map antigen expression profiles across different cell lines, while pharmaceutical efficacy is validated through in vitro tumor cell cytotoxicity and in vivo antitumor activity in cell-derived xenograft (CDX) models. Results: The ICE DAC platform enables comprehensive evaluation of early-stage DAC discovery projects, encompassing degrader payload screening, antibody/DAC bioanalysis, and efficacy assessment from in vitro to in vivo settings. Conclusion: With 15 years of experience in early drug discovery—from target validation to preclinical candidate identification—ICE offers screening and evaluation services to support clients in verifying the efficacy and mechanism of action of degrader payloads, antibodies and DACs. This support significantly accelerates clients’ DAC research and development timelines. Citation Format: Fan Huang, Rui Song, Zhiwei Bao, Tong Wu, Jiangtao Lin, Qian Wang, Xiaojian Wang, Li Li, Ying Meng, Tiejun Bing. Degrader-Antibody Conjugate Platform: Experimental Capabilities in Characterization and Evaluation – Fom In Vitro Assays to In Vivo Studies [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B136.