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Human African Trypanosomiasis Translation

  • Target disease: HAT
  • Partners: SCYNEXIS Inc., USA; Anacor Pharmaceuticals, USA; Advinus Therapeutics, India; Penn Pharma, UK
  • Leadership: Discovery and Pre-clinical Director: Robert Don; Head of HAT Clinical Programme: Antoine Tarral; Clinical Manager: Séverine Blesson; Head of Pharmaceutical Development: Steve Robinson; Project Coordinator: Delphine Launay
  • Project start: January 2010
  • Funding: Bill & Melinda Gates Foundation, USA; Department for International Development (DFID), UK; Dutch Ministry of Foreign Affairs (DGIS), the Netherlands; Federal Ministry of Education and Research (BMBF through KfW), Germany; Médecins Sans Frontières/Doctors without Borders, International; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland

  • Objective: Progress the clinical development of SCYX-7158 for the treatment of stage 2 HAT caused by T.b. gambiense, as well as for stage 1 HAT and HAT caused by T.b. rhodesiense

SCYX-7158 belongs to a unique boron-based chemical class, the oxaboroles, which was originally provided by Anacor Pharmaceuticals and screened for activity against T. brucei at the University of California San Francisco. A unique collaboration between DNDi, Anacor Pharmaceuticals (a biopharmaceutical company in Palo Alto, California, USA) and SCYNEXIS (a drug discovery and development company based in Research Triangle Park, North Carolina, USA), within a consortium that also included Pace University (USA) and Swiss TPH, enabled the identification of SCYX-7158, selected as a promising preclinical candidate in late 2009. In pre-clinical studies, SCYX-7158 was shown to be safe and efficacious to treat stage 2 HAT, as it is able to cross the blood-brain barrier. Pre-clinical development progressed success fully through 2010, and all pre-clinical data were published in PLoS NTDs in June 2011.(1) Batches of drug substance and drug product (capsules) were produced according to current good manufacturing practices (cGMP) and supplied for the Phase I clinical trial. In 2012, a robust tablet formulation was also developed in order to supply Phase II/III clinical trials, and manufacturing is planned for mid-2013.

Following clearance by the French ethics committee and regulatory authority, SCYX-7158 entered first-in-human studies in March 2012 and became DNDi’s first entity resulting from its own lead optimization efforts to enter Phase I clinical studies. These studies are performed in order to assess its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers of sub-Saharan origin. Following the first dose of SCYX-7158, pharmacokinetic results showed a longer than expected half-life in human plasma. Additional cohorts in humans assessed the safety profile, and following results from the intermediate dog study, the ascending dose study re-started in early 2013.

(1) Jacobs RT. et al. (2011) SCYX-7158, an orally-active benzoxaborole for the treatment of stage 2 human African trypanosomiasis. PLoS Negl Trop Dis 5: e1151.

Last update: October 2013

Tags: HAT – Sleeping Sickness
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