Chagas Translation

 

  • Target disease: Chagas disease
  • Partners: University of California San Francisco (UCSF), USA
  • Leadership: Head of Drug Discovery: Eric Chatelain; Project Coordinator: Stéphanie Braillard
  • Project start: September 2010
  • Funding (since project start): Dutch Ministry of Foreign Affairs (DGIS), The Netherlands; National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID), USA; BBVA Foundation, Spain; Other private foundations and individuals.
  • Project Status: Completed

 

Objective:

  • Complete 28-day toxicity study in non-human primates
  • Complete IND package

 

K777 is a vinyl sulfone cysteine protease inhibitor, which inhibits cruzain, a key protease required for the survival of T. cruzi. K777 was originally characterized by the Sandler Center for Research in Tropical Parasitic Disease at UCSF and has since been shown to be safe and efficacious in animal models of acute and chronic Chagas disease. The main objective of the project was to perform the required pre-clinical studies (safety pharmacology and toxicology) in order to complete the IND package for clinical evaluation of K777 for the treatment of Chagas disease. Safety pharmacology studies were completed, and no effects on electrocardiogram (ECG) or respiratory function were observed, even at the high dose. Dose Range Finding/Maximum Tolerated Dose (DRF/MTD) in non-human primates and a 28-day toxicity study was scheduled to be performed in 2013, but on the recommendation of the DNDi Scientific Advisory Committee in mid-2013, this project was stopped due to tolerability findings at low dose in primates and dogs.

Last update: September 2014