Oxaborole SCYX-7158 (HAT)

• Target disease: HAT • Partners: Anacor Pharmaceuticals Inc., USA; Scynexis Inc., USA; Pace University, USA; Sandler Center of the University of California, USA; Swiss Tropical and Public Health Institute, Switzerland; Advinus Therapeutics, India; SGS Aster, France. • Management: Head of HAT Clinical Programme, Antoine Tarral; Project Coordinators, Ivan Scandale, Delphine Launay, Séverine Blesson • Project start: December 2007 • Funding: Bill & Melinda Gates Foundation, USA; Médecins Sans Frontières/Doctors without Borders, International; Spanish Agency for International Development Cooperation (AECID), Spain; Department for International Development (DFID), UK; individual donors.

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Status: Oxaboroles, provided by Anacor – the originator of this unique boron-based chemical class – were identified as hits against T. brucei at the Sandler Center of the University of California San Francisco, and have shown activity in animal models of sleeping sickness. From the 400 compounds synthesized at SCYNEXIS and the additional 330 compounds from the Anacor libraries screened, some compounds cured murine central nervous system infection but were actively transported from the brain and had to be administered at high doses. New compounds that are not effluxed from the brain have since been identified. One of these compounds, SCYX-7158, was advanced as a preclinical candidate at the end of 2009. In 2010, the pre-clinical development progressed successfully. In particular, the early non-GLP safety studies demonstrated no issues of concern. Thus, a regulatory toxicology package was performed in 2011. The drug manufacturing and the documentation for the start of clinical development were finalized end of 2011 and submitted to authorities to get their clearance for starting First in Human Phase I trial. The first administration of the drug candidate SCYX-7158 occurred in March 2012. This is DNDi’s first new chemical entity issued from lead optimization to enter into Phase I studies.