Leishmaniasis Translational platform 

The Leishmaniasis Translational Platform aims to bridge pre-clinical research and clinical development by generating the data and models needed to optimize treatment regimens for both cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). The programme integrates innovative pre-clinical models (bioluminescent imaging or BLI), pharmacokinetic/pharmacodynamic (PK/PD) analyses, skin exposure assessments, and translational modelling approaches to support evidence-based decision-making throughout the drug development process.

For CL, the project focuses on understanding drug distribution and activity within infected skin lesions to better predict clinical efficacy. Bioluminescent imaging models using clinically relevant Leishmania species have been established and applied to evaluate both standard-of-care treatments and novel DNDi compounds (such as DNDI-0690 and DNDI-6174). These studies, combined with PK/PD and physiologically based pharmacokinetic (PBPK) modelling, have enabled improved prediction of human efficacious doses and identification of clinically relevant systemic and skin pharmacokinetic targets to support future Phase II trials.

For VL, the platform is evaluating the potential of combination therapies involving the most advanced drug candidates in the pipeline, in particular LXE408 and DNDI-6899. Using highly sensitive bioluminescent imaging models, the project assesses whether combinations provide additive or synergistic benefits while identifying any potential antagonistic interactions. The resulting translational PK/PD framework supports human dose projection and regimen selection, helping to accelerate the development of safe, effective, and patient-friendly combination therapies for leishmaniasis.

The knowledge and methodologies generated through this work are being shared with the wider scientific community to strengthen translational research and advance the development of new treatments for people living with leishmaniasis worldwide.