R&D MODEL & PORTFOLIO
with similar gene sequences to the parasites). In total over 17,000 compounds have been provided by the companies and organizations listed below, in addition to the commercial MicroSource library. This effort yielded a considerable number of hits in the low micromolar range. However, further work is needed to make optimized antifilarial drugs before progressing any candidate into preclinical development. Resources for this project are mainly dedicated to profiling molecules
from the optimisation programmes undertaken by AbbVie and Celgene.
PARTNERS: The Hospital of Bonn, Institute for Medical Microbiology, Immunology & Parasitology (IMMIP), Germany; the Muséum National d’Histoire Naturelle Paris, France; and the Northwick Park Institute for Medical Research (NPIMR), UK
MAIN COMPOUND LIBRARIES: AbbVie, USA; AstraZeneca, UK; BASF, Germany; Bristol-Myers Squibb (BMS), USA; Celgene, USA; GSK, Tres Cantos, Spain; E.I. DuPont Nemours, USA; Epichem, Australia; Janssen, Belgium; Mercachem, The Netherlands; Merck, USA; Merck Serono, Germany; MMV, Switzerland; National Institutes of Health (NIH), USA; Novartis Centre de la Recherche Santé Animale, Switzerland; Sanofi, France; TB Alliance, USA; WuXi AppTech, China
NTD Drug Discovery Booster to speed up compounds identification
OVERALL OBJECTIVE: Speed up
the process and cut the cost of finding new treatments for leishmaniasis and Chagas Disease
OBJECTIVE 2015: Implement the NTD Drug
Discovery Booster project with 3-6 pharmaceutical companies
The NTD Drug Discovery Booster was launched in analogues 2015 as an experiment tested aimed at speeding up the process and cutting the cost of finding new treatments for Chagas disease and leishmaniasis. Initially, the project brought together DNDi and four pharmaceutical companies: Eisai Co Ltd, Shionogi & Co Ltd, Takeda Pharmaceutical Ltd, and AstraZeneca plc.
The chemical universe around a DNDi lead molecule (red) is explored through sharing of molecules in pharma companies databases (green, cyan, yellow, purple spheres).
DNDi supplies active “seed” compounds used by each company for in silico searches of chemical libraries for structurally-related compounds and entirely novel chemical scaffolds. The most interesting compounds are selected and undergo further testing in vitro to assess potency. In a multilateral, simultaneous search process across the pharmaceutical companies, DND i accesses millions of compounds, generated over decades of research. Identification of novel chemical entities acts as a starting point for optimization of potential treatments or cures for these diseases. The innovation of the Drug Discovery Booster not only lies in the multilateral and cross-company comparative approach, but also in the iterative nature of the search, in which companies continue to examine their compound libraries for better compound matches as the search is refined. This will significantly reduce the time it will take to find new, promising treatment leads.
NTD Drug Discovery Booster meeting in Tokyo with partners’ representatives, November 2015.
By the end of 2015, six seed compounds had been submitted to the Booster for the first round of in silico screening and then the identified analogues were tested in vitro by the Institut Pasteur Korea and showed improvements in potency or the identification of novel chemical scaffolds. Further iterations will seek to build on these initial results. Celgene joined the consortium in 2016, and it is hoped that more companies will join in the future.
PARTNERS: AstraZeneca, UK; Celgene, USA (since 2016); Eisai, Japan; Shionogi, Japan; Takeda Pharmaceutical, Japan
DNDi Annual Report 2015 › 21