A comprehensive evaluation of the human Tg32 and Tg276 FcRn transgenic mouse and non-human primate models for predicting antibody pharmacokinetics in human

Key Points

• This research aims to evaluate the Tg276 and Tg32 mouse models for their ability to predict antibody pharmacokinetics in humans.
• Utilized a Tg276 transgenic mouse model, including an immunocompromised variant to reduce anti-drug antibodies.
• Compared translational performance of Tg276 and Tg32 models against non-human primates (NHP).
• Assessed predicted clearance rates from both mouse models and evaluated their utility for preclinical antibody screening.
• The Tg276 hemizygous model shows comparable and sometimes superior predicted clearance compared to the Tg32 homozygous strain and NHP.
• Findings support the Tg276 model's use for early-stage antibody screening and lead optimization.
• Demonstrated effectiveness in mitigating anti-drug antibody responses with the immunocompromised Tg276 model.