S07 series

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.