- Target disease: Chagas
- Main partners (since project start): AbbVie, USA; AstraZeneca, UK; Brazilian Biosciences National Laboratory, Brazil; Centre for Drug Candidate Optimization, Monash University, Australia; Drug Discovery Unit, University of Dundee, UK; Epichem, Australia; Eisai Co., Ltd., Japan; Griffith Institute for Drug Discovery (formerly Eskitis Institute for Cell and Molecular Therapies), Australia; Fundaçao de Apoio Universidade Federale de Sao Paolo, Brazil; GlaxoSmithKline, UK; Griffith University, Australia; Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Belgium; Institut Pasteur Korea, South Korea; London School of Hygiene & Tropical Medicine, UK; Merck, USA; Shionogi & Co., Ltd., Japan; Sanofi, France; Sandexis, UK; Takeda Pharmaceutical Company Ltd., Japan; The Swiss Tropical and Public Health Institute, Switzerland; TCG Life Sciences, India; Instituto de Física, Universidad Sao Paolo, Brazil; Instituto de Química, University Estadual of Campinas, Brazil; WuXi AppTech, China.
- Project start: Ongoing
- Funding (since project start): Australian Research Council (ARC), Australia; Department for International Development (DFID), UK; Médecins Sans Frontières/Doctors without Borders, International; Ministry of Health, Brazil.
Multiple hits from screening with several pharmaceutical partners or from other sources have been progressed into hit confirmation and expansion studies. Several promising series, issued from the published hit list from “GSK Kinetoplastid Boxes” and Celgene, have been identified and are currently moving into the Hit-to-Lead stage; one series showed Proof of Principle in vivo and is in Lead Optimization. In order to identify hit series with a different mechanism of action, the screening cascade has been modified to filter out potential CYP51 inhibitors (same mechanism of action as posaconazole or ravuconazole), and prioritizing trypanocidal compounds early on. The insights gained from additional in vitro assays, coupled with a new in vivo model based on bioluminescent imaging, was developed at the LSHTM. The model predicts the outcome of benznidazole and posaconazole in clinical trials, enabling compounds to be moved forward with more confidence.
Opportunities for new candidates to include in the pipeline are continually under review. Preliminary mapping and set-up of discovery activities are continuing in Latin America in accordance with the global DNDi strategy of empowerment of, and funding from, the regional offices.
DNDi has continued its efforts in screening chemically diverse libraries for identification and confirmation of new hits that could progress and feed the H2L pipeline. In 2018, a new partnership was established with the Drug Discovery Unit from Dundee University in Scotland and GSK to jointly characterize and progress new promising hits.
A new discovery cascade has been implemented comprising new in vitro and in vivo If promising activity is demonstrated, the identified series would then be advanced into full lead optimization programmes.
Last update: February 2019