Translational Challenges From Nonclinical to Clinical Program: Case Study Examples

Abstract

Drug discovery and development is a complex, lengthy, and expensive process that takes on average 10-15 years and approximately $1-2 billion USD for approval of a new drug. While the studies needed to support clinical development are generally outlined in guidance documents, there is much less guidance on how to translate the nonclinical data into clinical designs. Nonclinical studies are performed to conduct the First-in-Human clinical trial, which is the first major milestone to advance new promising drug candidates, and are conducted primarily to determine the safe dose range for clinical development. Resolving how to move forward, and even when to move forward, requires significant cross-functional collaboration with pathologists, ADME scientists, biologists, and clinical staff. There are many reasons why drug candidates may fail; these could be as simple as insufficient understanding of the nature of the translational process, failure to effectively integrate the data from different pharmacologically relevant species, or erosion of the margin of safety during chronic toxicology studies. The case studies described here were designed to help participants in the 2024 American College of Toxicology (ACT) Continuing Education course “Translational Challenges from Nonclinical to Clinical Program: Case Study Examples” to improve their skills in managing translational challenges from nonclinical to clinical program encountered during drug development.