Papzimeos: what was done before first-in-human, and what came after?

“Repeat administration of a dose level approximately 5-fold higher than the intended clinical dose, assuming a 60-kilogram adult of 5x1011 PU (1x1010 VP/mouse/dose) of PRGN-2012 once weekly on Days 0, 7, and 14 was well tolerated in WT C57BL/6 mice with no safety findings reported at termination after 21 Days.”

“Local tolerance and systemic toxicity were assessed as part of the repeat dose toxicity study of PRGN-2012 in wild type (WT) C57BL/6 mice. PRGN-2012 or GC46.empty vector was administered once weekly for three weeks at 1×1010 VP/administration.”

“GLP Status No”

“No biodistribution (BD), genotoxicity, carcinogenicity, reproductive and developmental toxicity, juvenile, nor dedicated local tolerance studies of PRGN-2012 were conducted. These studies are not warranted based on the product characteristics and nonclinical safety profile of PRGN-2012.”

“This reviewer agrees with the rationale provided by the applicant for not conducting developmental and reproductive toxicology studies.”

“This reviewer agrees with the rationale provided by the applicant for not conducting developmental and reproductive toxicology studies.”

“No biodistribution (BD), genotoxicity, carcinogenicity, reproductive and developmental toxicity, juvenile, nor dedicated local tolerance studies of PRGN-2012 were conducted.”

“Per the applicant, studies were not conducted to evaluate carcinogenicity as adenovectors are non-integrating. Therefore, the risk for insertional mutagenesis is not a major concern.”

“This reviewer agrees with the rationale provided by the applicant for not conducting carcinogenicity/tumorigenicity studies.”