Waskyra: which tox species, and why?

“Two different WAS disease models were used to evaluate in vivo safety of transduced HSPCs: a WAS knockout (WKO) mouse on a C57BL/6 background”

“The impossibility of using autologous human cells in animal models limits the scope of possible nonclinical studies.”

“In both models, the test article was comprised of a mouse surrogate test article”

“Thus, two different WAS disease models were used to evaluate in vivo safety of transduced HSPCs: a WAS knockout (WKO) mouse on a C57BL/6 background, which required sublethal irradiation conditioning for transduced cell engraftment and a WKO mouse on SV129 background that required lethal irradiation conditioning.”

“The absence of standard developmental and reproductive toxicity studies with Telethon003 is acceptable in view of the patient population, nature of the gene therapy, and preconditioning regimen with developmental toxicants.”

“Traditional carcinogenicity studies were not conducted since they are not suitable for assessment of this drug product type.”

“In both models, the test article was a lineage-deficient (Lin-) HSPCs transduced with either the w1.6W or the w1.6W_mut6 (clinical) vector.”