Choosing which drug targets to pursue for a given disease is one of the most impactful decisions made in the global development of new medicines. This study examines the extent to which the outcomes of clinical trials can be predicted based on a small set of longitudinal (temporally labeled) evidence and properties of drug targets and diseases. We demonstrate a novel statistical learning framework for identifying the top 2% of target-disease pairs that are as much as 4-5x more likely to advance beyond phase 2 trials. This framework is 1.5-2x more effective than an Open Targets composite score based on the same set of evidence. It is also 2x more effective than a common measure for genetic support that has been observed previously, as well as in this study, to confer a 2x higher likelihood of success. Utilizing a subset of our biomedical evidence base, non-negative linear models resulting from this framework can produce simple weighting schemes across various types of human, animal, and cell model genomic, transcriptomic, proteomic, and clinical evidence to identify previously undeveloped target-disease pairs poised for clinical success. In this study we further explore: i) how longitudinal treatment of evidence relates to leakage and reverse causality in biomedical research and how temporalized evidence can mitigate common forms of potential biases and inflation ii) the relative impact of different types of features on our predictions; and iii) an analysis of the space of currently undeveloped, tractable targets predicted with these methods to have the highest likelihood of clinical success. To ease reproduction and deployment, no data is used outside of Open Targets and the described methods require no expert knowledge, and can support expansion of lines of evidence to further improve performance.