NTD Drug Discovery Booster, Achievements and Next Steps

Abstract

The Neglected Tropical Disease (NTD) Drug Discovery Booster is a collaborative project in early small molecule drug discovery running since 2015 between Drugs for Neglected Diseases initiative (DNDi) and pharmaceutical partners across the globe, including Astellas Pharma Ltd., Eisai Co., Ltd., Shionogi & Co., Ltd. and Takeda Pharmaceutical Company Ltd. in Japan, along with AbbVie Inc., Merck KGaA, AstraZeneca plc and Celgene Corporation. The Booster engages these partners to share both their experience with in silico screening as well as their proprietary chemical libraries to further develop new starting points for NTDs such as visceral leishmaniasis and Chagas disease. This collaborative approach allows DNDi to access new chemical space and elaborate the structure activity relationships (SAR) around phenotypic screening hits against the causative parasites of these diseases (Trypanosoma cruzi, Leishmania donovani and infantum) as well as access new starting points via innovative scaffold hops proposed by the partners. Since 2015 the Booster has probed over 20 new starting point "hits" for these diseases, successfully converting over half into new series for further exploitation. These series were developed further in partnership with the booster collaborators to enable in vivo proof of concept studies, with series from the booster progressing into lead optimization. Our efforts in the NTD Discovery Booster have demonstrated clear advantages of this precompetitive sharing mechanism and the synergistic value of exploring multiple proprietary compound libraries in parallel. The most advanced of these Booster projects is projected to deliver a preclinical candidate for leishmaniasis within the next 2 years.