Abstract A107: Accelerating and Advancing Targeted Therapeutics: A One-Stop Service Platform for ADC and Next-Generation Conjugate Development

Abstract Introduction: Antibody-drug conjugates (ADCs) harness the target specificity of monoclonal antibodies with the potency of cytotoxic agents, offering significant advantages over traditional chemotherapy and targeted therapies. Despite their promises, ADCs face challenges such as limited tumor penetration due to large molecular size, drug resistance development, off-target toxicity, and inefficient payload release. To overcome these limitations, next-generation conjugated drugs (XDCs) are being developed to improve therapeutic safety and efficacy. Methods and Results: With robust synthetic chemistry, bioconjugation expertise, advanced analytics, and full-process CDMO services, MedChemExpress (MCE) has established a one-stop platform for ADC/XDC development. Our platform supports a wide range of conjugation strategies, including non-site-specific methods (e.g., cysteine and lysine-based), site-specific methods (e.g., disulfide re-bridging, unnatural amino acid incorporation), as well as glycan-specific conjugation via oxidative or glycosidase modification. Besides conjugation, we have extensive expertise in linker-payload synthesis and structural optimization. To reduce systemic toxicity, immune-stimulating antibody conjugates (ISACs) have emerged as a class of XDCs by using non-cytotoxic payloads such as toll-like receptor (TLR) and STING agonists to activate the immune system within the tumor microenvironment. Our expertise in linker-payload synthesis and structural modification supports the development of novel immunotherapeutics. Furthermore, with a dedicated peptide synthesis facility, we have the capacity of developing peptide-drug conjugates (PDCs), which have improved tumor penetration. In gene-based therapy, we perform high-quality oligonucleotide synthesis, including nucleic acid modification, and antibody-oligonucleotide conjugation (AOCs). Finally, our analytical platform enables comprehensive quality testing of ADC/XDCs, including drug-to-antibody ratio (DAR), size-exclusion chromatography (SEC), free-drug quantification, endotoxin level, and concentration. Our CDMO system supports end-to-end ADC/XDC development, from synthesis to GMP-compliant clinical and commercial manufacturing, meeting regulatory standards in the U.S., the EU, and China. One of our milestone products is the total synthesis of Eribulin (CAS: 441045-17-6), covering process development, pilot production, GMP verification at the hundred-gram scale, and stability testing. To date, we have served over 800 clients, contributed to 50+ CMC projects, and supported 5 BLA applications and 12 secondary DMF filings. Conclusion: By leveraging multidisciplinary expertise and a fully integrated platform, MCE delivers comprehensive and efficient one-stop services for ADC/XDC development, empowering biopharma partners to accelerate and advance next-generation targeted therapies. Citation Format: Wei Li. Accelerating and Advancing Targeted Therapeutics: A One-Stop Service Platform for ADC and Next-Generation Conjugate Development [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 A107.