Wayrilz: which tox species, and why?

“the rat and dog were considered appropriate primary models for nonclinical safety studies, based on the similarity of oral bioavailability and metabolite profiles in these species to”

“This is because mouse, rat, dog, and rabbit BTK are nearly identical to the human version of the protein (approximately 99% homologous amino acid sequence), with no differences in the sites where rilzabrutinib binds.”

“Study 1281-16100: Nine-Month Oral GLP Toxicity Study of Rilzabrutinib in Beagle Dogs”

“repeat-dose toxicity studies in rats (13-day; 2-week; 1-, 3-, and 6-month), and dogs (4-day; 2- and 12-week, 1-, 3-, and 9-month)”

“reproductive toxicology studies (male and female fertility study in rats; embryo-fetal toxicity in rats and rabbits, pre- and postnatal development toxicity study in rats)”

“Rilzabrutinib was not carcinogenic in a 6-month study in Tg.rasH2 mice at doses up to 300 mg/kg/day. In a 2-year rat carcinogenicity study at doses of 10, 30 or 100 and 5, 15 or 50 mg/kg/day in males and females, respectively, there were no rilzabrutinib-related tumors.”

“This is because mouse, rat, dog, and rabbit BTK are nearly identical to the human version of the protein (approximately 99% homologous amino acid sequence), with no differences in the sites where rilzabrutinib binds.”