- Target disease: Leishmaniasis
- Main partners (since project start): Accelera, Italy; Advinus Therapeutics Ltd, India; Aptuit, Italy; Auckland University, New Zealand; Drug Discovery Unit, University of Dundee, UK; Hypha Discovery Ltd, UK; Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Belgium; London School of Hygiene & Tropical Medicine, UK; TB Alliance, USA; Penn Pharmaceuticals Services, UK; Syngene, India; WuXi AppTech, China.
- Project start: September 2015
- Funding (since project start): Bill & Melinda Gates Foundation, USA; Department for International Development (DFID), UK; Federal Ministry of Education and Research (BMBF through KfW); Médecins Sans Frontières/Doctors without Borders; Special Programme for Research and Training in Tropical Diseases (WHO-TDR), Switzerland; Swiss Agency for Development and Cooperation (SDC), Switzerland.
Nitroimidazole derivatives hold great potential to address unmet needs in tuberculosis (TB) therapy. As well as developing a clinical candidate for TB, the TB Alliance instituted a backup programme to maximize the potential of this class of anti-bacterial agents.Through a contractual agreement with TB Alliance, DNDi gained access to a library of around 70 nitroimidazoles which were then tested for potential anti-leishmanial activity.
Following the termination of the VL-2098 project in early 2015, two lead compounds from the nitroimidazooxazine back-up programme were progressed. One of these, DNDI-0690, showed good to excellent activity in vitro against both visceral leishmaniasis and cutaneous leishmaniasis causing strains of Leishmania and was nominated as a preclinical candidate in September 2015.
DNDI-0690 and other potential lead compounds for visceral leishmaniasis were 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.
A decision to progress to Phase I single ascending dose in healthy volunteers was agreed in 2018. A clinical trial application for a first-in-human study (Phase I) was submitted to UK authorities in February 2019.
A full preclinical toxicology and safety studies package was completed in 2017. The decision to progress to Phase I Single Ascending Dose in healthy volunteers was agreed in January 2018.
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: August 2019