DNDI-0690

Activities related to the clinical development of DNDI-0690 remained on hold.

Additional in vitro investigations were conducted to understand the underlying mechanism causing temporary biological abnormalities in some Phase I multiple-ascending dose study participants, but the mechanism was not fully elucidated. Reliably predicting the frequency of occurrence and potential severity of these abnormalities in leishmaniasis patients remains challenging. With other compounds currently under investigation for leishmaniasis in the DNDi portfolio presenting superior safety profiles, activities related to the clinical development of DNDI-0690 were placed on hold.

The evaluation of the safety and pharmacokinetic properties of DNDI-0690 after multiple dosing in healthy subjects was completed in 2022. Some biological abnormalities were observed in the subjects exposed to the treatment for 10 days, and additional in vitro investigations were conducted to understand the underlying mechanism. After several potential mechanisms were ruled out, the drug has been advanced for consideration for efficacy testing in leishmaniasis patients. Evaluation of the pharmacokinetic profile of the new tablet formulation will proceed when the required funding is secured.

A Phase I multiple ascending dose study of DNDI-0690 initiated in late 2020 enrolled 45 healthy adults and dosing of the drug from 5 to 10 consecutive days was completed towards the end of 2021. Results are currently being analysed and the final report is expected mid-2022. A new tablet formulation, better adapted to use in the field, has been developed and manufactured with a view to launching proof-of-concept studies in patients.

A Phase I multiple ascending dose study of DNDI-0690 was initiated in late 2020. Study completion is expected in late 2021.

A Phase I single ascending dose study in healthy volunteers was initiated in 2019; a multiple ascending dose study is planned for 2020.

A decision to progress to Phase I single ascending dose in healthy volunteers was agreed in 2018. A clinical trial application for a first-in-human study (Phase I) was submitted to UK authorities in February 2019.

A full preclinical toxicology and safety studies package was completed in 2017. The decision to progress to Phase I Single Ascending Dose in healthy volunteers was agreed in January 2018.

In 2016, DNDi activities focused on pharmaceutical development activities (drug substance and drug product development and manufacture), launching of toxicity/safety pre-IND package with dose range finding studies, as well as refinement of ADME, 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.