Screening leishmaniasis

DNDi has completed its high-throughput screening (HTS) programme testing compounds for activity against Leishmania donovani in collaboration with University of Tokyo and with support from the Global Health Innovative Technology (GHIT) Fund. A total of 11 hits belonging to seven chemical series were identified. The three most attractive scaffolds were followed up via the purchase and testing of 88 chemical analogues at the Swiss Tropical and Public Health Institute and the University of Tokyo. Unfortunately, none of the compounds showed significant activity against Leishmania donovani.

DNDi maintained a similar strategy of decreased leishmaniasis screening activities in 2023. However, the fully funded collaboration with University of Tokyo to establish high-throughput screening (HTS) for leishmaniasis in Japan continued with ongoing screening of the Drug Discovery Initiative collection of 220,000 compounds. The HTS programme was completed in March 2023, and a four-month funding extension was obtained from the Global Health Innovative Technology (GHIT) Fund to confirm the activity of and further characterize the three most promising chemical series identified through the project.

DNDi maintained decreased leishmaniasis screening activities, with the exception of its fully funded collaboration with University of Tokyo to establish high-throughput screening (HTS) capacity for leishmaniasis in Japan and to complete the screening of the Drug Discovery Initiative (DDI) collection of 220,000 compounds. The HTS Leishmania extracellular amastigote assay was developed at University of Tokyo and the single-dose screening of the entire DDI collection was completed in 2022.

With a robust portfolio of new chemical entities for leishmaniasis advancing to clinical trials, DNDi decided to progressively decrease leishmaniasis screening efforts in early 2021 to enable a greater emphasis on Chagas disease screening. However, screening of a limited number of natural product collections has been completed or is ongoing. A new, fully funded collaboration with University of Tokyo to establish screening capacity for leishmaniasis in Japan has also been initiated. The discovery team will continue to evaluate the potential benefit of new screening or discovery opportunities related to leishmaniasis. 

Several new collections originating from pharmaceutical and research partners were identified, contractually and physically accessed, and screened. Discussions continued with various pharmaceutical companies, not-for-profit organisations, and other entities to obtain access to new collections to keep building our screening pipeline. The COVID-19 pandemic delayed the activities of almost all our screening partners from mid-March 2020 through the end of the year. 

DNDi has identified a variety of novel hit series via the screening of new compound libraries to continuously feed the early discovery pipeline for leishmaniasis. Those new starting points originate from both natural product and synthetic compound collections, either accessed through partnerships, acquired via purchase, or obtained as in-kind contributions to DNDi. 

Several new starting points are currently being followed up in hit profiling, annotation, and hit-to-lead programmes. The screening effort will continue, with the aim of delivering further drug candidates to mitigate the risks of attrition and increase the chance of developing a new drug.

More than 20 novel series were identified in 2017 and are now being progressed.