Preclinical and Clinical Development of SJ733, a Novel PfATP4 Inhibitor for the Treatment of Severe Malaria

Severe malaria (SM) is a medical emergency requiring immediate parenteral or enteral treatment. SM affects two million people per year. The current WHO treatment of choice is IV or rectal Artesunate (AS), available in about 40 developing countries. AS is not registered in the US, Europe, Australia, Japan, as well as many other countries. Other SM treatments have significant liabilities (efficacy/tolerability). SJ733 is an antimalarial entering Phase 2 for oral 3- day treatment of non-severe malaria. In humans, SJ733 is active against blood and sexual stages and possesses an excellent safety profile. SJ733 demonstrated rapid parasite killing in a Phase 1b human challenge. Animal models indicate a lack of EFD toxicity. SJ733’s clinical profile makes SJ733 a strong candidate for the treatment of SM. Herein, we propose to explore SJ733 as a novel treatment for SM. Formulation studies will minimize dose volume for parental use. Preclinically, dog was the most sensitive toxicology species. Therefore, GLP dog toxicity studies will bridge from existing IND to the proposed route and schedule. The clinical work will focus on examining safety, tolerability, and pharmacokinetics for two dosing schedules: a bolus IV schedule mirroring AS use and a continuous infusion schedule.