Biotransformation assessments for therapeutic proteins to-date have largely focused on characterizing amino acid post-translational modifications (PTMs) located in critical regions, proteolytic degradation and glycation or glycosylation . For ADCs, linker/payload stability is often the focus of biotransformation characterization . Payload chemical modification such as deacetylation, adduct formation and partial cleavage have been reported. However, the existing gaps in our understanding of ADC SAR make it essential to further elucidate ADC biotransformation profile of the three critical components determining ADC SAR: the protein scaffold, the conjugation site, and the conjugated payload.