Zalmoxis: which tox species, and why?

“Two studies in two different GvHD animal models both based on the NOD/SCID system were performed to evaluate the PK and primary PD of MM-TK.”

“The MM-TK DP is a species specific product and therefore standard carcinogenicity studies using rodents or non-human primates as described in the ICH guidelines are not appropriate.”

“NOD/SCID mice subcutaneously transplanted with human skin were also used so that the direct evaluation of allogeneic GvHD response against the grafted human skin could be observed.”

“To evaluate safety and functional properties of MM-TK, the Applicant developed an integrated approach which included both in vivo pharmacodynamic, toxicology and kinetic data concurrently obtained taking advantage of two different immunodeficient mouse models for Graft versus Host Disease (GvHD) based on the Non-Obese Diabetes/Severe Compromised Immunodeficient (NOD/SCID) mouse system”

“The lack of studies on reproductive and development toxicity is justified.”

“The MM-TK DP is a species specific product and therefore standard carcinogenicity studies using rodents or non-human primates as described in the ICH guidelines are not appropriate.”

“Preclinical in vitro and in vivo studies in immune deficient mice were performed using for cell preparation both the SFCMM-3 #35 retroviral vector and an optimized version of the vector”