Human Pharmacokinetic Prediction of Antibody‐Drug Conjugates Using Human <scp>FcRn</scp> Transgenic Mice

ABSTRACT Antibody‐drug conjugates (ADCs) have progressed significantly in recent years, particularly in the oncology field. However, predicting human pharmacokinetics (PK) of ADCs in the early stages of drug development remains challenging. Human neonatal Fc receptor (FcRn) transgenic mice have been established as a reliable pre‐clinical PK model for predicting human PK profiles of antibody‐based therapeutics. In this study, we investigated the applicability of human FcRn transgenic mice for predicting the human PK of ADCs in a pre‐clinical setting. Eight FDA‐approved ADCs were administered to human FcRn transgenic mice, and PK parameters were calculated using two‐compartment model analysis. The clearance (CL) values of total ADCs in human FcRn transgenic mice showed a strong correlation with human CL ( R 2 = 0.888). Single‐species allometric scaling using data from human FcRn transgenic mice indicated an optimal exponent of 1.0 for predicting human CL, with 87.5% of ADCs falling within twofold of the human CL. These findings indicate that allometric scaling from human FcRn transgenic mice serves as a promising translational tool for predicting human CL of ADCs from the early development stage.