Libtayo: which tox species, and why?

“In in vitro studies, cemiplimab (REGN2810) bound to human and cynomolgus monkey PD-1 with similar affinity, but did not bind rodent PD-1, supporting the use of cynomolgus monkeys as the single pharmacologically relevant species for toxicity assessment.”

“REGN2810 exhibited similar binding affinity for human and cynomolgus monkey PD-1 (see Table 2), but did not bind mouse or rat PD-1, supporting the use of cynomolgus monkeys as a pharmacologically relevant species for toxicity assessment.”

“Since REGN2810 does not bind mouse PD-1, mice were genetically engineered to express a human/mouse PD-1 chimeric receptor (huPD-1 mice); these mice have a functional human PD-1 with expression regulated by the mouse PD-1 promoter.”

“The toxicity of cemiplimab was evaluated in the repeat dose toxicity studies of 4, 13 and 26-weeks duration in monkeys.”

“No effects on fertility assessment parameters or in the male and female reproductive organs were observed in a 3-month repeat dose fertility assessment study with sexually mature cynomolgus monkeys.”

“Carcinogenicity studies were not conducted or required to support the use of an antibody in the currently proposed indication per ICH S9.”

“Since REGN2810 does not bind mouse PD-1, mice were genetically engineered to express a human/mouse PD-1 chimeric receptor (huPD-1 mice); these mice have a functional human PD-1 with expression regulated by the mouse PD-1 promoter.”