Symposium Sessions
Day 1, June 10（Wed.） 14:40-15:00 Room A (5F 503)
- 1A-S1-1440
Bioanalysis and Biotransformation of Antibody-Drug Conjugate
(Daiichi-Sankyo)
oYoko Urasaki
Antibody-drug conjugates (ADCs) consist of monoclonal antibodies covalently linked to cytotoxic payloads via chemical linkers, enabling selective drug delivery with enhanced efficacy and reduced systemic toxicity. In pharmacokinetic evaluation, three analytes are typically quantified in plasma: ADC, total antibody, and unconjugated payload, using ligand binding assay (LBA) and LC-MS/MS. However, these analytes alone are insufficient to characterize temporal changes in the drug-to-antibody ratio (DAR), which are critical for understanding therapeutic durability and safety profiles.
To address this, quantification of antibody-conjugated payload (ac-payload) using hybrid immunoprecipitation-LC/MS has gained attention. Dividing ac-payload concentration by total antibody concentration enables in vivo DAR monitoring, providing a comprehensive understanding of ADC disposition.
Using trastuzumab deruxtecan (T-DXd) as a model compound, this presentation details the pharmacokinetic profiles of four analytes and DAR changes in nonclinical species. Additionally, biotransformation studies focusing on linker-payload conjugation sites will be presented to elucidate mechanisms underlying DAR changes. These integrated approaches support T-DXd development and contribute to establishing an analytical platform for next-generation ADC drug discovery.