Discovery of Novel N -Linked Camptothecin Linker-Payloads to Access Antibody–Drug Conjugates with High Target-Mediated In Vivo Efficacy

-aminobenzyl carbamate (PABC) linkers with a focus on stability and polarity leads to the discovery of promising α-amino-isobutyramido-exatecan constructs. The corresponding high-DAR ADCs showed low aggregation, good in vitro potency, and robust target-mediated efficacy in vivo across two antibody-antigen pairs. These results demonstrate the potential of these linker-payloads and the broad applicability of this design strategy.