Drug developers face challenges in translating preclinical findings to safe and effective human trials. Traditionally,
preclinical testing relies on a phased approach that combines simple in vitro assays and whole animal in vivo studies; however, a translational gap remains between these findings and the clinical outcomes.
The translational gap is caused by the limited ability of simple in vitro assays to accurately predict human responses, combined with the interspecies limitations of animal studies, a core requirement by global regulatory
bodies before human trials, unless no suitable model exists. The transition from preclinical models to human subjects therefore requires navigating complex pharmacokinetic (PK) and toxicology uncertainties that vary significantly by drug modality and therapeutic area.
Our inability to adequately address these uncertainties is represented by consistently high drug attrition rates. Toxicity remains one of the most significant causes of drug attrition, accounting for 30% of drug failures in the clinic.1 Poor human translation in pre-clinical PK studies is also a major driver of clinical failures, with PK and bioavailability listed as the third most common cause of attrition and 16% of all failures.2
