In this presentation, Dr. Kamendi shares key considerations for an IND submission, noting the lack of established best practices. The goal of nonclinical drug development is to match the right patient population with the right drug, properties, dose, and timing. The process begins with building the target product profile (TPP) sheet. Other important factors include:

• In vitro and in vivo ADME, and secondary pharmacology including organ-specific toxicology.
• Drug biodistribution studies.
• Tolerability  especially for systemic delivery routes like intravenous, intramuscular, subcutaneous, or topical. 
• Target-mediated toxicity to identify the optimal balance between efficacy and acceptable toxicity. 
• Secondary pharmacology studies assess off-target binding and cardiovascular effects mediated by hERG and other ion channels.

Non-GLP toxicology programs typically involve clinical observations of drug effects and macroscopic examination of organs in two species. Once pharmacology and toxicology studies are complete, the IND can be filed, but nonclinical studies, such as carcinogenicity and abuse liability, must continue. For systemic and local administration of gene therapy, it is necessary to assess the systemic effect of the transgene before moving forward with full toxicology studies.