LeishmaniasisResearch

 

  • Target disease: Leishmaniasis
  • Main partners (since project start): AbbVie, USA; Charles River, France; Centre for Drug Candidate Optimisation (CDCO), Monash University, Australia; Eurofins CEREP, France; Eurofins Pharma Discovery Services (formerly Eurofins Panlabs), USA; Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Belgium; London School of Hygiene & Tropical Medicine, UK; Pfizer, USA; Sandexis, UK; Takeda Pharmaceutical Company Ltd., Japan; WuXi AppTech, China.
  • Project start: February 2012
  • Funding (since project start): Department for International Development (DFID), UK; Global Health Innovative Technology (GHIT) Fund, Japan.

 

Overall objective: 

  • Select a pre-clinical candidate from the aminopyrazole series for the treatment of leishmaniasis.

 

The aminopyrazole class of compounds originally from Pfizer has shown promising early profiles for the treatment of both visceral leishmaniasis and cutaneous leishmaniasis. Profiling of current and new leads in a panel of drug-sensitive and drug-resistant strains of Leishmania, exploration of the in vivo dose response, pharmacokinetics, and initial in vitro safety assays are all underway. The ongoing lead optimization programme in collaboration with Takeda and supported by the GHIT Fund aims to select an optimized lead.

 

Further work on the back-ups from this series is currently on hold as efforts focus on the lead compound DNDI-5561. However, new chemical spaces continue to be investigated through the Open Synthesis Network, a collaborative project that engages master’s and undergraduate students in research for neglected diseases.

DNDI-5561 was nominated as a new pre-clinical candidate from the aminopyrazole series in October 2017. Four back-up compounds are well advanced and offer similar profiles to DNDI-5561. Additional studies, including preliminary toxicology assessments, are being planned to further understand the safety profiles of these compounds and to identify the best back-up to DNDI-5561. 

Preparation of active pharmaceutical ingredient (API) and formulation for the second generation leads to enable the exploratory toxicology studies early 2017.

The project moved into the lead optimization stage in January 2015, with GHIT Fund support and expert scientific assistance from Takeda from April 2015.

 

Last update: August 2019