DNDi’s screening of Anacor’s library of drug compounds from the oxaborole class, followed by focused medicinal chemistry efforts, led to the discovery of a number of analogues showing efficacy in animal models of Chagas disease, leishmaniasis, and sleeping sickness.

One of these compounds, acoziborole, is currently progressing through Phase II/III trials for sleeping sickness. An analogue compound, DNDI-6148, emerged as a promising lead candidate and was shown to be effective against Leishmania strains in various in vitro and in vivo studies. In late 2018, the decision was made to progress DNDI-6148 to a first-in-human Phase I single ascending dose study in healthy volunteers.

Project updates

2020

A Phase I single ascending dose study continued through 2020 but faced delays due to the COVID-19 pandemic. Study completion is expected in Q4 2021, and a multiple ascending dose study will follow in 2022.

2019

The clinical trial application for this study was approved in November 2019 and the first volunteer was enrolled in a Phase I single ascending dose study in January 2020. Pending study results, a multiple ascending dose study will start in late 2020.

2018

The decision was made in 2018 to progress to a Phase I single ascending dose in healthy volunteers in parallel with additional toxicological investigations. A clinical trial application for a first-in-human study (Phase I) was submitted to the French authorities in October.

2017

The pre-clinical toxicology package was completed in 2017, and the decision was made to progress to Phase I single ascending dose in healthy volunteers in parallel with additional toxicological investigations.

2016

In January 2016, DNDI-6148, from the oxaborole class, was nominated as a pre-clinical candidate for the treatment of visceral leishmaniasis. Pharmaceutical development activities (drug substance and drug product development and manufacture) have now been initiated, and the toxicity/safety pre-IND package was launched starting with dose range finding studies, along with refinement of ADME (absorption, distribution, metabolism and elimination), efficacy and safety profile to ensure a smooth transition from the pre-clinical phase to Phase I clinical phase, which should happen over the course of 2017.