R&D MODEL & PORTFOLIO
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 ani-
mal 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 “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.
The Chemistry Team of Prof. Dr. Luiz Carlos Dias (centre), UNICAMP.
DNDi Annual Report 2015 › 19