Status: Nitroimidazoles, a class of novel anti-bacterial agents, have great potential for addressing major unmet medical needs in TB therapy. PA-824, the first compound in the TB Alliance portfolio is currently undergoing Phase II clinical development for the treatment of TB. It has many attractive characteristics as a TB therapy.

Through a contractual agreement with TB Alliance, DNDi was granted access to their nitroimidazole library. From the initially selected 70 nitroimidazoles belonging to 4 chemical subclasses, DNDi-VL-2098 was identified as a very potent and safe molecule and was selected for in-depth evaluation of its efficacy, pharmacokinetic, and early safety profile on the basis of these preliminary results. This compound is potent and selective in vitro and shows efficacy in acute and chronic VL animal models. Appropriate exposure is obtained after oral dosing in rodents and the compound does not induce toxicity after one-week administration at several times the efficacious dose. The objective is to perform all pre-clinical activities needed to meet regulatory requirements, and to file an Investigational New Drug (IND) by the end of 2011 if further pre-clinical data support advancement to clinical.