Siliq: which tox species, and why?

“Repeat-dose toxicity studies were performed in cynomolgus monkeys, because comparable potency was shown for brodalumab for the inhibition of monkey IL-17RA compared to human IL-17RA”

“because comparable potency was shown for brodalumab for the inhibition of monkey IL-17RA compared to human IL-17RA, whereas brodalumab does not cross-react with rodent IL-17RA and assessment of binding to dog IL-17RA was inconclusive.”

“In order to demonstrate the proof of concept, in vivo activity was investigated using surrogate antibodies against mouse IL-17RA.”

“Repeat-dose toxicity studies were performed in cynomolgus monkeys, because comparable potency was shown for brodalumab for the inhibition of monkey IL-17RA compared to human IL-17RA, whereas brodalumab does not cross-react with rodent IL-17RA and assessment of binding to dog IL-17RA was inconclusive.”

“Reproductive and developmental toxicity studies included a dose range-finding study in rabbits and an enhanced pre- and postnatal developmental toxicity study in cynomolgus monkeys. The rabbit study was limited by immunogenicity and the rabbit was not further used for evaluation of reproductive and developmental toxicity.”

“No genetic toxicity or carcinogenicity studies have been conducted with brodalumab.”

“Surrogate antibodies that were used were M750, a rat anti-mouse IL-17RA monoclonal antibody IgG2b, and M751, a chimeric rat anti-mouse IL-17RA monoclonal antibody with a mouse IgG1.”