Penpulimab: which tox species, and why?

“In in vitro studies, penpulimab bound to human and cynomolgus monkey PD-1 but did not bind rodent PD-1, supporting the use of cynomolgus monkeys as the single pharmacologically relevant species for toxicity assessment.”

“with EC50 values of 0.053 and 0.215 nM, respectively, but did not bind to mouse or rat PD-1, supporting the use of cynomolgus monkeys as a pharmacologically relevant species for toxicity assessment.”

“Given that pempulimab does not bind mouse PD-1, the Applicant investigated the in vivo antitumor activity of pempulimab in a human PD-1 knock-in genetically engineered mouse model (HuGEMM)”

“The Applicant evaluated the safety of penpulimab in cynomolgus monkeys in GLP-compliant repeat-dose toxicology studies of up to 13 weeks duration.”

“No reproductive or embryo-fetal developmental toxicology studies were conducted with penpulimab. Rather, the Applicant provided a literature-based assessment of the potential reproductive toxicity of penpulimab”

“FDA agrees that carcinogenicity studies are not needed to support the use of penpulimab in the currently proposed indication per ICH S9.”

“Given that pempulimab does not bind mouse PD-1, the Applicant investigated the in vivo antitumor activity of pempulimab in a human PD-1 knock-in genetically engineered mouse model (HuGEMM)”