Model-based drug discovery: implementation and impact

•Implementation of quantitative pharmacology strategy to discovery drug projects.•Building dedicated preclinical M&S capability.•Developing a companywide infrastructure for flexible data management and use.•Facilitation of rational decision making, increased efficiency and reduced cycle times and costs.

Model-based drug discovery (MBDDx) aims to build and continuously improve the quantitative understanding of the relation between drug exposure (target engagement) efficacy and safety, to support target validation; to define compound property criteria for lead optimization and safety margins; to set the starting dose; and to predict human dose and scheduling for clinical candidates alone, or in combination with other medicines. AstraZeneca has systematically implemented MBDDx within all drug discovery programs, with a focused investment to build a preclinical modeling and simulation capability and an in vivo information platform and architecture, the implementation, impact and learning of which are discussed here.