RT Journal Article SR Electronic T1 Development of human target validation classification that predicts future clinical efficacy JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP jpet.118.250894 DO 10.1124/jpet.118.250894 A1 Cecilia Karlsson A1 Peter J Greasley A1 David Gustafsson A1 Karin Wahlander YR 2018 UL http://jpet.aspetjournals.org/content/early/2018/11/27/jpet.118.250894.abstract AB Fewer new medicines have become available to patients during the last decades. Clinical efficacy failures in late phase development have been identified as a common cause of this decline. Improved ways to ensure early selection of the right drug targets when it comes to efficacy is therefore a highly desirable goal. The aim of this work was to develop a strategy to facilitate selection of novel targets already in the discovery phase which later on in clinical development would demonstrate efficacy. A cross-functional team at AstraZeneca with extensive experience of drug discovery and development participated in several workshops to identify the critical elements that contribute to building human target validation (HTV; the relevance of the target from a human perspective). The elements were consolidated into a ten-point HTV classification system that was ranked from lowest to highest in terms of perceived impact on future clinical efficacy. Using fifty years of legacy research and development (R&D) data the ability of the ten-point HTV classification to predict future clinical efficacy was evaluated. Drug targets were classified as having low, medium or high HTV at the time of candidate drug (CD) selection. Comparing this HTV classification with later clinical development efficacy data showed that HTV classification was highly predictive of future clinical efficacy success. This new strategy for HTV assessment provides a novel approach to early prediction of clinical efficacy and a better understanding of portfolio risk.