Kygevvi: which tox species, and why?

“The nonclinical safety program supporting the clinical development and approval of doxecitine and doxribtimine included repeat-dose oral toxicity studies in mice (up to 4 weeks), rats (up to 6 months), and dogs (up to 3 months)”

“The studies, conducted in alignment with ICH guidelines, utilized mouse, rat, rabbit, and dog models, leveraging shared mitochondrial TK2 nucleoside phosphorylation and cytosolic nucleoside pathways, as well as conserved mitochondrial genomes and incorporation pathways analogous to those in humans.”

“In dogs, doxecitine and doxribtimine up to 100 mg/kg/day (doxecitine 50 mg/kg/day and doxribtimine 50 mg/kg/day) for 13 weeks.”

“The nonclinical safety program supporting the clinical development and approval of doxecitine and doxribtimine included repeat-dose oral toxicity studies in mice (up to 4 weeks), rats (up to 6 months), and dogs (up to 3 months)”

“reproductive and developmental toxicity assessment including a fertility and early embryonic development study in rats, embryofetal development studies in both rats and rabbits, and a juvenile animal study in rats”

“To address the remaining nonclinical data gaps, the Applicant will conduct the following postapproval studies: a 9-month dog study and a 26-week carcinogenicity study in Tg-rasH2 mice with doxecitine and doxribtimine”

“The studies, conducted in alignment with ICH guidelines, utilized mouse, rat, rabbit, and dog models, leveraging shared mitochondrial TK2 nucleoside phosphorylation and cytosolic nucleoside pathways, as well as conserved mitochondrial genomes and incorporation pathways analogous to those in humans.”