Developing the first innovative treatments against visceral leishmaniasis (360G-Wellcome-315018_Z_24_Z)

Visceral leishmaniasis (VL) affects some of the poorest people on Earth. Prone to outbreaks and fuelled by environmental and climate changes, WHO estimates 50,000 to 90,000 cases per year, 50% are children. VL is fatal if untreated. The drugs currently available to treat VL have been repurposed for this indication and have severe limitations, such as toxicity and parenteral routes of administration. In 2018, DNDi gathered the drug candidates for VL from different groups and, together with partners, progressed a portfolio of compounds along the R&D pathway. Today, LXE408, a kinetoplastid proteasome inhibitor, is the most advanced of these candidates, progressing in Phase 2 development in India (positive interim analysis in April 2024) and Ethiopia (first patient recruited in April 2024). DNDI-6899, a Leishmania CRK12 inhibitor, is the next most promising drug candidate, currently in Phase 1 development. These drug candidates have the potential to bring true innovation to patients: an oral, safe and efficacious treatment delivered at primary health care centres, close to communities, especially in Africa where a treatment combination is expected to be required. The three-year project will enable the progress of LXE408 and DNDI-6899 to prepare for Phase 2/3 in East Africa by mid-2027.