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This paper analyses the emergence and development of the Medicon Valley biomedicine cluster from an evolutionary perspective. We focus on the co-evolution and synergies among the drivers of the cluster's emergence. Targeting biomed involves some challenges and complexities, which are particularly strong in this case, owing to its specificities (bi-national nature, predominant context of horizontal policies, pre-existent pharma industry). The main aim is to analyse the role of the different institutional players in this policy process. The study suggests that targeting emerges from regional coordination bodies. It also reveals a smart specialisation strategy ‘avant la lettre’ and shows a number of critical insights for the implementation of this policy approach.