A pipeline of promise
Narrowing in on the next-generation medicines patients deserve
From our earliest days, DNDi teams and partners have worked along two tracks to deliver new treatments for neglected patients. The first makes the most of medicines already available by replacing toxic treatments that require long hospital stays with shorter, safer formulations and combinations that improve outcomes, limit side effects, and allow patients to return to family and work sooner.
The second harnesses the best science to get patients what they have deserved all along: simple, safe, and effective oral medicines, purpose-built to be easy to access and administer in remote settings where neglected diseases hit hardest. This longer-term journey starts in the lab, screening compounds to identify those with the potential to hit the mark, and advances from early drug discovery through the long R&D lifecycle and into the hands of doctors and patients. That long game is challenging for neglected infectious diseases, requiring resources and commitment in a field long sidelined by traditional industry players. But the rewards can be huge: hope, healing, and security for communities long excluded from the benefits of medical innovation, relief for overstretched health systems, and clear pathways to sustainable disease elimination.
Acoziborole: proof the long game pays off
The clearest evidence yet that long-term determination delivers has just left the pipeline. In February 2026, acoziborole – a single-dose oral cure for the most common form of sleeping sickness – received a positive opinion from the European Medicines Agency. Within weeks, the Democratic Republic of the Congo (DRC) – long the epicentre of the nightmare disease – registered the treatment, which will also help other endemic countries in West and Central Africa accelerate access.
It is hard to overstate the monumental leap this represents. Twenty years ago, the only treatment option for late-stage sleeping sickness was an arsenic derivative so toxic it killed one in twenty patients. A determination to overcome this unacceptable treatment gap drove doctors from MSF to push for DNDi’s creation in the early 2000s.
The first new treatment to emerge from DNDi’s own lead optimization programme, acoziborole was initially identified in the chemical library of Anacor Pharmaceuticals before being optimized in partnership with Scynexis and Pace University. Developed with Sanofi and the national sleeping sickness control programmes of the DRC and Guinea, it is administered at the point of care as a single dose of three tablets – replacing injections, hospitalization, and treatments requiring complex laboratory staging.
In the late 1990s, nearly 40,000 cases of gambiense sleeping sickness were reported, with an estimated 300,000 undiagnosed. Hard-fought national strategies and improved treatments delivered by DNDi and partners have helped bring reported cases down to just 600 in 2024. The simplicity of acoziborole will help diagnose and cure remaining scattered cases in remote, hard-to-reach communities and reach the final mile to sustainably eliminate a disease that has killed millions in Africa over the past century.
MONICA, from West Pokot County, Kenya, received two and a half weeks of painful daily injections when she fell ill with visceral leishmaniasis. The treatment saved her life but required hospitalization far from home and her seven children.
LXE408: a first-in-class compound for leishmaniasis
Visceral leishmaniasis (VL) is the second deadliest parasitic disease after malaria. For decades, its treatment has required weeks-long hospital stays and painful injections of toxic, heavy-metal-based drugs – a punishing ordeal for patients and their families.
LXE408 selectively disables a protein-recycling system (the proteasome) of the parasite that causes VL, without which it cannot survive, and that could enable a different future for patients. A short course of tablets administered at clinics close to home would be transformational – especially in Eastern Africa, now home to more than 70% of the world’s VL cases. If proven safe and effective, its simplicity could also help power regional efforts to eliminate the disease.
Advanced by DNDi in partnership with Novartis, LXE408 completed two Phase II proof-of-concept studies in India and Ethiopia in 2025, with early data showing promising efficacy and safety. Full results will be released in late 2026, and planning for a pivotal Phase III trial in Eastern Africa and further studies in South Asia is underway. Its impact could extend further: a separate Phase II study set to begin in Latin America will test LXE408 for the treatment of cutaneous leishmaniasis, a disfiguring, stigmatizing skin form of the disease with scarce treatment options.
The push for all-new treatments for Chagas disease
An estimated 8 million people, mostly in Latin America, are living with Chagas disease. It often hides for decades, damaging the heart and digestive system long before patients feel unwell. Around a third develop life-threatening complications. Although they remain the best option and access must be improved, current treatments can cause significant side effects and are not suitable for women who are – or could become – pregnant.
Our teams and partners have focused on drug discovery for new Chagas treatments for two decades; today, there is reason for cautious optimism. Beyond leishmaniasis, LXE408 has shown promising pre-clinical results for Chagas, and Novartis is conducting a Phase II study in patients with chronic Chagas disease in Latin America and the US.
Another exciting contender, AN2-502998, offers fresh hope of a cure for chronic Chagas infection in the form of safe, oral treatment. Discovered at the University of Georgia, with follow-on development at AN2 Therapeutics, pre-clinical testing showed the candidate can achieve full parasite clearance, and a Phase I trial in healthy volunteers found it safe and well-tolerated. It belongs to the same boron-based chemical family as acoziborole and acts on the same validated parasite target. Drawing on DNDi’s extensive network of clinical-trial sites in Latin America, a Phase II proof-of-concept study is set to begin in late 2026 in partnership with AN2.
Running in parallel is a quietly transformative effort: our collaboration with InfYnity Biomarkers to develop the MultiCruzi assay, a simple, reliable ‘test of cure’. Recognized as DNDi’s 2025 pre-clinical Project of the Year, the collaboration could remove major obstacles to proving new Chagas treatments work, which would facilitate registration and access to any new treatments developed.
Going the distance
Like every innovation in the making at DNDi, this progress is the product of bold collaboration and steady commitment from patients, partners, and supporters who share in our conviction that all people should benefit from scientific progress. At a moment of unprecedented flux in global health cooperation, we are grateful for the many hands holding steady to keep the pipeline flowing to fruition.
More 2025 highlights:
Photo credits: Yaw Afrim Gyebi-DNDi; Lameck Ododo-DNDi.
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