Ziihera: which tox species, and why?

“The toxicology program was carried out in cynomolgus monkeys, as it was demonstrated that the cynomolgus monkey and human have relevant HER2 sequence homology and affinity.”

“It was demonstrated that zanidatamab binds with similar affinity to human and cynomolgus monkey HER2 ECD (Kd = 0.74 and 0.47 nM, respectively), while the affinity for dog was lower (Kd = 4.07 nM) and no affinity was demonstrated for rodents”

“The cynomolgus monkey is considered a suitable species for characterizing the PK of zanidatamab as it binds both human and monkey HER2 molecules with similar subnanomolar affinity.”

“The cynomolgus monkey was selected as the most relevant species for toxicology testing based on considerations of sequence homology and affinity binding to HER2.”

“Consequently, the conduct of de novo developmental and reproductive toxicity (DART) studies is not warranted for zanidatamab.”

“No carcinogenicity studies have been conducted with zanidatamab.”

“The toxicology program was carried out in cynomolgus monkeys, as it was demonstrated that the cynomolgus monkey and human have relevant HER2 sequence homology and affinity.”