Preclinical studies to enable first in human clinical trials

Abstract

Drug discovery is a multidisciplinary process which requires a coordinated effort to deliver a drug candidate with appropriate pharmaceutical properties and a clear therapeutic paradigm. Identifying a suitable target for therapeutic intervention requires careful biological and technical assessments to ensure its validity and druggability. Optimal screening strategies must be established to identify tractable hit matter. A robust test cascade enables triage and optimisation of compounds for further evaluation in models of increasing complexity. The ability to relate target engagement and phenotypic effect provides proof of concept in early studies. Investigation of the pharmacokinetic and pharmacodynamic properties in preclinical models facilitates prediction of suitable exposure in patients with an appropriate formulation and scheduling. Toxicology studies establish an acceptable safety margin for the product. Understanding of the clinical context in which to best use the development compound i.e. patient populations, resistance mechanism and combination strategies pave the way for a successful clinical development.