DNDi and our partners are searching for shorter, safer, more effective treatments to stop a silent killer. In the short term, we are working to develop improved treatment regimens with the existing drug benznidazole, reduce mother-to-child transmission, and help roll out ‘test-and-treat’ strategies to reach people living with Chagas disease in remote areas of Latin America. Our longer-term goal is to discover and develop entirely new drug candidates, with the aim of launching at least one Phase III trial by 2028.
Our progress in 2025 includes:
Drug discovery
Screening: Early-stage discovery activities centred on the screening of original compound libraries in partnership with Institute Pasteur Korea, University of Dundee, and Nagasaki University enabled the identification of more than ten new T. cruzi-active hit series for our Chagas disease discovery programme. High-throughput screening was successfully completed for four synthetic compound collections: the 60,000-compound diversity set from BINDS/University of Osaka, the 40,000-compound collection from Shionogi, the 25,000-compound HGL3 collection from Medicines for Malaria Venture, and the 38,000-compound diversity collection from Nagoya. On the natural products front, our collaborative screening efforts with the Kitasato Institute and University of Tokyo are progressing as planned. In parallel, we are working with our partner laboratories to develop next-generation T. cruzi assay systems. These advancements will enable us to make better-informed decisions when selecting the most promising series to progress through our Chagas discovery pipeline, with a particular focus on achieving cidality and sterile cure.
Hit-to-lead: DNDi reorganized its early-stage Chagas discovery portfolio at the beginning of 2025 to streamline processes and leverage resources to increase efficiency while reducing costs and turnaround time. Multiple lead optimization consortia were brought together into a single global hit-to-lead and lead optimization consortium focused on Chagas disease. This complementary network streamlines the hit-to-lead journey, encourages knowledge sharing, reduces differences in data across labs, and improves oversight of the global portfolio – ultimately increasing the chances of finding a suitable candidate. Within this framework, a diverse set of chemical series have been de-risked for unwanted mechanisms and are being advanced with encouraging results.
UW series: DNDi and partners at the University of Dundee’s Drug Discovery Unit and the University of Washington prioritized compounds with the strongest profiles and suitability for development, with the specific goal of moving an optimized lead into exploratory safety studies. The project remains on track towards nominating a preclinical candidate, while ensuring compounds with innovative modes of action are present in the R&D pipeline for new treatments for Chagas disease.
Series-5824 (MT): The Chagas disease lead optimization project made considerable progress in 2025, with more than 150 compounds synthesized in collaboration with Tanabe Pharma. We maintained our medicinal chemistry strategy, focusing on enhancing T. cruzi activity while improving the drug metabolism and pharmacokinetic properties of the series to address safety risks. Significant advancements were made in identifying the series’ mechanism of action, thanks to expert support from the Centre for Medicines Discovery at the University of Oxford, and the University of Dundee.
Open Synthesis Network: Work on projects P1Tc and P5 have been finalized, and a new project, P9, has been added to the OSN portfolio. A manuscript detailing the findings from project P1Tc led by the University of Nottingham was published in the journal ACS Infectious Diseases. In addition, Prof. Pascal Marchand of the Université de Nantes was recognized with the French Society for Medicinal Chemistry’s Camille Wermuth Award 2025 for his work using the OSN in teaching undergraduate medicinal chemistry students.
Open Chagas: The project received 21 proposals from Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay. Of these, 13 are led by women, and the projects were evenly distributed across three areas: small molecules, natural products, and drug repurposing or therapeutic combinations. Stage 1 of the project was completed in August 2025, followed by the start of Stage 2. An Open Chagas Workshop will be conducted with participants selected in Stage 1, with support from the United Nations University Biotechnology Programme for Latin America and the Caribbean (UNU-BIOLAC).
Translational research
Biomarkers: Additional analyses of data generated from the BENDITA and E1224 studies were conducted to 1) evaluate the MultiCruzi assay as a tool to measure antibody decline as a proxy for parasitological cure in adult patients with Chagas disease and 2) assess the suitability of the measure as a primary endpoint in registrational trials. A complementary study with CONICET in Argentina examined whether antibody decline measured with the MultiCruzi assay correlated with later seroreversion in children. A collaborative research project with Novartis was launched to identify potential host biomarkers using proteomics and MultiCruzi platforms, and work continued in the review of the current biomarkers landscape for Chagas disease and the development of target product profiles for Chagas disease biomarker assays. The project was recognized by the DNDi Scientific Advisory Committee as the organization’s 2025 Project of the Year in pre-clinical research.
DNDI-6148: Activities related to the clinical development of DNDI-6148 remain on hold.
Clinical trials
New benznidazole regimens: NuestroBen – a Phase III clinical trial testing shorter regimens of benznidazole for the treatment of Chagas disease – continued recruitment in Argentina. The efficacy analysis for this study was planned to include data from a similar study led by Fiocruz in Bolivia and Colombia. That study was cancelled, however, and the sample size for the NuestroBen clinical trial was increased from 300 to 540 participants. NuestroBen has also been expanded to Bolivia to achieve regional scope. Recruitment is expected to be completed by the second quarter of 2027, with the main study results expected to be available towards the end of 2028
Registration & access
Chagas Access Project: In a major milestone, Colombia adopted the use of rapid diagnostic tests (RDTs) and included them in the country’s official diagnostic algorithms for the first time. Implementation research projects that include the use of RDTs began in Argentina and Guatemala. A study assessing the performance of RDTs in pregnant women in Colombia was completed. Implementation research studies focusing on intercultural approaches, as well as monitoring and evaluation activities, were started in Guatemala and Colombia, with significant achievements in therapeutic gap analyses. Monitoring and evaluation activities were also initiated in Bolivia. A study assessing the acceptability of contraception among woman receiving treatment for Chagas disease in the context of clinical trials or medical intervention began in Colombia.
Photo credit: Neil Branvold-DNDi
