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• Academic drug discovery offers great opportunities but has challenges in prioritisation and funding. • We describe a paradigm for academic drug discovery with two key features: • Effective identification, evaluation, and management of projects with translational potential by experts in drug discovery and development; • Targeted resources to create a diverse and derisked portfolio of projects ready for investment. • The ideas and concepts discussed may be of interest to other academic institutions and consortia. There are many different approaches to drug discovery in academia, some of which are based broadly on the industrial model of discovering novel targets and then conducting screening within academic drug discovery centres to identify hit molecules. Here we describe our approach to drug discovery, which makes more efficient use of the capabilities and resources of the different stakeholders. Specifically, we have created a large portfolio of drug projects and conducted small amounts of derisking work to ensure projects are investment ready. In this feature we will describe this model, including its limitations and advantages, since we believe the ideas and concepts will be of interest to other academic institutions and consortia. [ABSTRACT FROM AUTHOR]