Rasonque: which tox species, and why?

“Repeat-dose toxicology studies were conducted in mice (4-weeks and 13-weeks) and monkeys (4-weeks and 13-weeks).”

“Mice and cynomolgus monkeys were considered the relevant test species for in vivo toxicology studies based on cross-species PK exposures, metabolic profiles, similar (mouse) or identical (monkey) binding affinity to human cyclophilin A (CypA), and identical cross-species KRAS protein sequence in the guanosine 5' triphosphatase (GTPase) domain to which daraxonrasib binds.”

“Daraxonrasib was administered once daily by oral gavage in repeat-dose studies to mice and monkeys in toxicity studies for up to 13-weeks in duration.”

“Repeat-dose toxicology studies were conducted in mice (4-weeks and 13-weeks) and monkeys (4-weeks and 13-weeks).”

“In an embryo-fetal development study in mice (25, 50, and 75 mg/kg/day), daraxonrasib caused embryo-fetal toxicity at ≥50 mg/kg/day (2.5x exposure at the recommended dose based on AUC).”

“Carcinogenicity studies were not conducted with daraxonrasib, consistent with ICH S9 recommendations for advanced cancer indications.”

“Daraxonrasib was administered once daily by oral gavage in repeat-dose studies to mice and monkeys in toxicity studies for up to 13-weeks in duration.”