As a result of an Ames positive result in a single salmonella strain (T98), the FDA is requiring that, prior to our pre-IND meeting with them, we perform a GLP Ames assay with a form of BPN-15606 (besylate salt form) that is equivalent to what will be used in our IND-enabling toxicity studies and Phase 1 clinical trials. In addition, the FDA recommended that we perform two additional in vivo gene toxicity assays in rodents: the Micronucleus assay and the Comet assay. This requires first converting the seven grams of the freebase form of BPN-15606 that we currently have available to the besylate salt form and characterizing this material with extensive analytical chemistry in order to show equivalence. The conversion chemistry (including analytical chemistry) will be carried out at Albany Molecular Research Inc. (AMRI). This will be a two-week process. The next step is to perform a GLP Ames assay with that material (besylate salt form of BPN-15606). The second step will be performing the in vivo Micronucleus and Comet genetic toxicology assays in rodents, which will be carried out at BioReliance. These three genetic toxicology tests will take approximately eight weeks. The final step is the bioanalytical analysis of the plasma samples collected from the rodents that underwent the in vivo Micronucleus and Comet assays. This is in order to confirm that the rodents were exposed to the compound. This bioanalytical analysis requires a validated GLP bioanalytical assay. These latter studies will be carried out at the Stanford Research Institute (SRI).
Acceleration of FDA-Required GLP Gene Toxicity Studies with the GSM BPN-15606
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