patients

R&D MODEL & PORTFOLIO
DISCOVERY
Drug discovery is a demanding process, particularly with the added constraints of working in a neglected
area and within a limited budget. The standard “black box” approach involves screening compounds
against parasites in vitro, to identify those which are able to kill the parasite under laboratory conditions.
Having identified initial hits, analogous
compounds are synthesized
and evaluated to identify even more
potent molecules in a process known
as hit-to-lead. The most promising
of these undergo further optimization
in order to maximize antiparasitic
activity, increase tolerability and
safety, and optimize the amount of
time a compound stays in the body.
With compounds undergoing clinical
development for HAT, DNDi’s
screening and lead optimization
efforts are currently focused on
identifying compounds for Chagas
and leishmaniasis.
The mini-portfolio approach for
filarial disease treatments aims to
identify: (1 ) direct-acting compounds
– by screening libraries from animal
health companies and repurposing
compounds for human use,
and (2 ) indirectly-acting compounds
– which kill the symbiotic Wolbachia
bacteria – in partnership with the
anti Wolbachia consortium (A-WOL)
at the Liverpool School of Tropical
Medicine, UK.
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 (see p. 21).
Medicinal chemistry with
partners in the North and South
Over the last decade, DNDi has
worked with academic and industrial
medicinal chemistry partners who
are organized geographically into
two consortia, in Australia (LO AUS)
and the United States (LO US).
In 2013 we began building a new
consortium in Latin America (LOLA),
providing support and mentoring for
young scientists in the region (see
below). The consortia undertake
hit-to-lead and lead optimization
activities for visceral leishmaniasis
and Chagas disease (see Leish
H2L p. 29, and Chagas H2L p. 38),
with HAT activities on hold in case
of any future need.
A Latin American consortium for leishmaniasis and Chagas disease drug discovery
The Chemistry Team of Prof. Dr. Luiz Carlos Dias (centre), UNICAMP.
The “Partnership of the Year
2015” was awarded to LOLA,
a Latin American Lead
Optimization Programme.
The LOLA project uses an
international collaborative
approach, working with
UNICAMP (University of
Campinas), Brazil, and with
partners in the USA (AbbVie)
and Europe (LMPH, University
of Antwerp, Belgium) to carry
out early stage drug discovery
and sets a precedent for all
emerging neglected disease
endemic countries.
DNDi Annual Report 2015 › 19