Leishmaniasis Translation

 

  • Target disease: VL
  • Main partners (since project start): London School of Hygiene and Tropical Medicine, UK; TB Alliance, USA; Auckland University, New Zealand; Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Belgium; WuXi AppTech, China; Aptuit, Italy; Accelera, Italy.
  • Project start: September 2015
  • Funding (since project start): Bill & Melinda Gates Foundation, USA; Department for International Development (DFID), UK; Médecins Sans Frontières/Doctors without Borders; Federal Ministry of Education and Research (BMBF through KfW).

 

Overall Objective:

  • Progress the pre-clinical development of DNDi-0690, a selected nitroimidazole for the treatment of VL and possibly CL.

 

Following the termination of the VL-2098 project in early 2015, the decision was taken to progress with lead compounds from two sub-series previously identified from the nitroimidazooxazine backup programme (DNDI-8219 and DNDI-0690) which had good efficacy in vivo, better solubility, and lower potential for cardiotoxic effects. A 14-day toxicity evaluation carried out in 2015 led to DNDI-0690 nomination as a pre-clinical candidate in September 2015.

In addition, with other potential lead compounds for VL, DNDI-0690 was profiled in vitro against CL-causing strains of Leishmania at the London School of Hygiene & Tropical Medicine and the Walter Reed Army Institute of Research and showed good to excellent activity, consistent with their activity against L. donovani and L. infantum.

In 2016, DNDi activities focused on pharmaceutical development activities (drug substance and drug product development and manufacture), launching of toxicity/safety pre-IND package with dose range finding studies, as well as refinement of ADME, efficacy and safety profile to ensure a smooth transition from the pre-clinical phase to Phase I clinical phase, which should happen over the course of 2017.

 

Last update: February 2017