This project originated from DNDi’s successful NTD Drug Discovery Booster programme. As a result of further collaboration with Takeda Pharmaceutical Company Limited to identify and advance novel compounds against visceral leishmaniasis, the S07 lead chemical series of compounds showed promising efficacy and safety profiles. DNDi and Takeda are collaborating on medicinal chemistry optimization of the S07 leads that have been identified, with the aim of progressing at least one optimized lead through to a pre-clinical candidate compound for visceral leishmaniasis, with funding support from Japan’s Global Health Innovative Technology Fund (GHIT Fund).

Project updates


Exploratory toxicology studies for the two selected optimized leads were performed and finalized at Accelera. While a no-observed-adverse-effect level (NOAEL) for one of the leads could not be determined, the second optimized lead fulfills the criteria of the target candidate profile for visceral leishmaniasis. The putative mechanism of action of parasite proteasome inhibition and selectivity against the human target were also confirmed for both S07 series compounds.


Scale-up of the two selected optimized leads was completed. Exploratory toxicity study activities began at Accelera, and bioanalytical method transfer and validation were completed. In-vivo studies with scaled-up lead compounds were initiated in January 2023.


Two optimized leads were identified that will move forward into exploratory toxicology studies before pre-candidate nomination. The current priority is synthesis route optimization and scale-up of the two optimized leads.  


The NTD Drug Discovery Booster identified two lead compounds from the S07 hit series that demonstrated efficacy in a leishmaniasis infection model. These two compounds advanced through to lead optimization and, in collaboration with Takeda, are now being further characterized.

Recent data suggest that these two lead compounds have the same mechanism of action as two other compounds currently in Phase I clinical trials: GSK3494245/DDD1305143, a compound being jointly developed by DNDi and GlaxoSmithKline.