Margenza: which tox species, and why?

“The Applicant conducted GLP-compliant 6-week (doses up to 150 mg/kg/dose) and 13-week (doses up to 100 mg/kg/dose) repeat-dose toxicology studies of margetuximab in cynomolgus monkeys.”

“In a molecular binding study applying SPR, margetuximab Fc domain showed enhanced binding to activating cynomolgus Fc receptors CD16A and CD32A but also increased binding to inhibitory Fc receptor CD32B.”

“Margetuximab was administered through IV infusion once weekly. No target organs for margetuximab were identified”

“The Applicant conducted GLP-compliant 6-week (doses up to 150 mg/kg/dose) and 13-week (doses up to 100 mg/kg/dose) repeat-dose toxicology studies of margetuximab in cynomolgus monkeys.”

“An enhanced pre- and postnatal development (ePPND) study was conducted in cynomolgus monkeys (Report 8329256) to evaluate potential effects of margetuximab on pregnancy, embryo-fetal development, parturition, and postnatal development.”

“Not performed per ICH S6(R1), ICH S1A, and ICH S9.”

“Margetuximab also showed dose-dependent enhanced activity against trastuzumab-resistant JIMT-1 compared to RES120 in a hCD16A knock-in transgenic mouse model expressing low-binding allele CD16A-158F”