patients

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
More than
1,600
analogues
tested
The NTD Drug Discovery
Booster was launched in
2015 as an experiment
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, DNDi 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