Drug discovery efforts for new Plasmodium vivax malaria curative therapy have been hindered by our relatively poor understanding of the parasite liver stage biology as well as the dearth of cellular and molecular tools. To evaluate drug efficacy on liver stages, there are animal model(s) of hypnozoite biology—P. cynomolgi in macaques and potentially P. vivax in Aotus monkeys—which are expensive and have very low throughput. Access to a surrogate in vitro cellular system would be thus very valuable for the rapid discovery of new drugs with potency on the Plasmodium liver stage. Recent progress has been made with the P. cynomolgi parasite that, when cultured in simian hepatocytes, develops persistent forms displaying all the pharmacological and biological properties of the hypnozoite. Through several collaborations, we have leveraged this assay to identify a novel series of antimalarial drugs that, through the inhibition of the plasmodium lipid kinase PI4K, kill all the main life-cycle stages of the parasite, including the hypnozoite. Unfortunately this in vitro assay remains of very low throughput and does not allow for large scale screening. In this context, the Novartis Institute for Tropical Diseases aims to develop and validate a technology platform for the high-throughput in vitro evaluation of drugs on Plasmodium’s liver stages, including the hypnozoite.