Oxachagas

DNDi is pursuing several oxaborole series optimization projects for kinetoplastid diseases, including Chagas disease. Following significant (between five and ten times) improvement in in vitro potency against T. cruzi, three oxaborole candidates were tested in a mouse model of Chagas disease at Murdoch University in 2013. These compounds produced similar reductions in parasitemia and increases in mouse survival to that observed with benznidazole, but did not produce a complete, or sterile, cure. Further profiling of oxaborole candidates is planned in new mouse models once validated, which are under development to include clinical insights into compound profiling resulting from the analysis of data from the E1224 proof-of-concept trial. Lead optimization of the oxaborole series for Chagas disease is now being managed by a new partnership between Anacor and the University of Georgia, which will work closely with the DNDi lead optimization project for leishmaniasis for this class in order to maximize cross-fertilization of ideas and leads.