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Quantifying the probability of pharmacological success to inform compound progression decisions
Xuan Zhou1, Ole Graff2, Chao Chen3
1Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, Shanghai, China.
Abstract:
The Probability of Pharmacology Success, or PoPS, is a powerful metric to inform progression decisions by quantifying a compound's overall pharmacological strength based on its mechanism. It is defined as the probability that X level of pharmacology is achieved in Y proportion of patients at a safe dose. The importance of adequate drug exposure, target engagement and functional pharmacology for enabling a compound's efficacy is widely recognized. The PoPS estimates how well these conditions are met by integrating the compound's pharmacological properties and the target's modulation needs for the intended indication, in a pharmacometric model that includes the knowledge uncertainty. We use examples to illustrate how it can be used to compare drug candidates under specified benefit and risk conditions, support first-in-human decisions based on exposure limits, advise preclinical lead optimisation, and define clinical-trial populations.
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