Leishmaniasis hit-to-lead

Activities related to hit generation and optimization for visceral leishmaniasis remain down-prioritized in favour of investment in other disease areas. However, the DNDi discovery team continued to contribute to target-based drug discovery and perform limited in vitro and in vivo profiling with external collaborators.

As a result of progress in current lead optimization and the pre-clinical candidate portfolio, hit generation for visceral leishmaniasis has been down prioritized in favour of investment in other disease areas. However, limited efforts were made in 2021 to profile and further progress some series as part of the lead optimization consortia (LOLA, LO AUS, LO US, and LOCI).  

More than 10 distinct series from various origins were progressed.

The process of hit-to-lead optimization is ongoing, with multiple series being progressed based on outputs of the screening programme. A variety of hit-to-lead mechanisms and exploration strategies are being used to progress towards in vivo proof-of-concept studies in pre-clinical efficacy models of leishmaniasis.

The process of hit-to-lead optimization is ongoing, with multiple series provided by several pharmaceutical companies as well as with hits from libraries purchased from commercial vendors and screened by DNDi. If promising activity can be demonstrated in pre-clinical models of leishmaniasis, the series will be advanced into full lead optimization.

The process of hit-to-lead optimization is ongoing with multiple series from several pharmaceutical companies and with hits from libraries purchased from commercial vendors and screened by DNDi to be advanced if promising activity can be shown in pre-clinical models.

The process of hit-to-lead optimization is ongoing with multiple series from several pharmaceutical companies and with hits from libraries purchased from commercial vendors and screened by DNDi to be advanced if promising activity can be shown in pre-clinical models.

A notable success in January 2015 was the successful advancement of the aminopyrazole series from the hit to lead stage into the next lead optimization stage. This early work has recently been published in J. Med. Chem. In addition, the NTD Drug Discovery Booster project commenced in April 2015 working with four pharmaceutical companies: Eisai, Shionogi, Takeda Pharmaceutical Company Limited, and Astra Zeneca and has so far conducted hit expansion on six different hits which are being developed for leishmaniasis and Chagas disease.

A number of pharmacokinetic and pharmacodynamic studies have been conducted in animal models of VL using existing and experimental drugs to build improved PK/PD models and ameliorate the translation of new drugs from discovery into clinical studies.