From Target Validation to Safety Evaluation: Navigating the ADC Development Pathway

Antibody–drug conjugates (ADCs) represent a promising therapeutic class that combines the specificity of antibodies with the potency of cytotoxic payloads. However, their inherent complexity—including structural heterogeneity, dynamic biotransformation, and variable drug-to-antibody ratios—poses significant challenges across the entire spectrum of discovery, bioanalysis, pharmacokinetics, and safety evaluation.

This webinar brings together experts to provide a comprehensive overview of the ADC development journey. It begins with approaches for target validation and lead optimization, including the use of humanized-mouse models to assess both antibodies and ADCs. The discussion then turns to analytical and DMPK challenges, exploring strategies to characterize ADC components and their transformations, with emphasis on techniques such as LC–MS, ligand binding assays, and hybrid methods to address the drug-antibody ratio (DAR), immunogenicity, and distribution.

Finally, the webinar highlights the critical stage of nonclinical safety evaluation, underscoring the need to assess both intact ADCs and novel payloads in relevant animal models. The complexities of on-target and off-target toxicities will be examined, along with strategies to mitigate clinical risks and enhance study design. To complement this, systematic strategies for clinical bioanalysis are presented, addressing issues such as stability, sensitivity, and non-specific interference.

Together, these topics aim to provide participants with an overall perspective of the scientific and regulatory considerations essential for advancing ADCs toward successful clinical development.