MMV390048 is an aminopyridine plasmodial PI4K inhibitor, selected as a Plasmodium blood-stage schizonticide for a next generation of malaria treatments to overcome resistance to current therapies. MMV390048 showed an acceptable preclinical safety profile and progressed up to Phase 2a clinical trials. However, embryofetal studies revealed adverse developmental toxicity signals, including diaphragmatic hernias and cardiovascular malformations in rats but not rabbits.