references
R&D MODEL & PORTFOLIO
HUMAN AFRICAN TRYPANOSOMIASIS / SLEEPING SICKNESS
RESEARCH
SCYX-1608210 and SCYX-1330682
PROJECT START: April 2007 and April 2009 respectively OVERALL OBJECTIVE: Progress a backup oxaborole into pre-clinical development 2015 OBJECTIVE: Retain as a back-up compound
in case of future need
Extensive pharmacokinetic profiling of possible oxaborole compounds led to the selection of SCYX-1608210 and SCYX-1330682, which demonstrated cure in the stage 2 mouse model of HAT, as a backup for SCYX-7158 in case of need. Given the current success of other projects for HAT, further development was put on hold in 2013 and will only recommence should problems be encountered with SCYX-7158 in clinical development.
PARTNERS: Anacor Pharmaceuticals Inc., Pace University, USA;
LMPH, Belgium; SCYNEXIS Inc., USA
TRANSLATION
SCYX-7158
PROJECT START: January 2010 OVERALL OBJECTIVE: Develop and register SCYX-7158 as a new, single dose, oral treatment for the treatment of stage 2 HAT caused by T. b. gambiense (g-HAT), ideally also for stage 1 2015 OBJECTIVE: Complete single-ascending dose study in healthy
human volunteers
An oxaborole originally provided by Anacor Pharmaceuticals was found to be active against HAT parasites at the University of California San Francisco, and further investigated by a consortium consisting of DNDi, Anacor, SCYNEXIS, Pace University, and Swiss TPH. Compound optimization over two years and examination of over 1,000 compounds produced SCYX7158 which was selected as a promising pre-clinical candidate for g-HAT in late 2009. In pre-clinical studies, SCYX-7158 was shown to be safe and efficacious in treating a brain form of the disease in animals, when administered orally in a single dose.
In March 2012, SCYX-7158 became DNDi’s first new chemical entity resulting from its own lead optimization programme, to enter clinical development. SCYX-7158 was found to have an unusually long half-life when tested in healthy volunteers. This Phase I study was finalized in March 2015 and results were presented later that year at the European Congress on Tropical Medicine and International Health in Basel. The singledose treatment will be tested in patients with stage 2 g-HAT in a Phase II/III trial, planned to start in the Democratic Republic of the Congo in 2016. The study will use several sites already active in fexinidazole development with addition of new sites selected from high-prevalence g-HAT areas. Patients will be followed up for 18 months after treatment to ensure long-lasting cure, with a preliminary evaluation of data performed after the first 12 months.
PARTNERS: Anacor Pharmaceuticals Inc., USA; Advinus Therapeutics
Ltd, India; SCYNEXIS Inc., USA; Institut de Recherche pour le Développement (IRD), France.
24 › DNDi Annual Report 2015
