UW series

The project remains one of the most advanced drug discovery projects in DNDi’s kinetoplastid portfolio. DNDi and partners University of Dundee Drug Discovery Unit, GSK, and the University of Washington continued to identify optimized leads from the UW series – a scaffold that shows good efficacy (no relapse after immunosuppression) in the Chagas bioluminescence chronic model – as well as multiple other chemical series that act through the same promising mode of action. 

DNDi continued work with the alliance to further optimize and de-risk a new generation of compounds related to the original UW series and chemically diverse backup series. 

Compound optimization of the UW series, aimed at the nomination of a pre-clinical candidate to advance to the next stage of development, progressed through 2022 with several leads showing improved properties and confirmation of single-compound cure in bioluminescent in vivo models. A chemically diverse backup series of compounds sharing the same putative mode of action were identified and are being optimized in parallel.

Compound optimization of the UW-series with a focus on optimizing the drug property profile of series compounds progressed significantly in 2021. A second generation of compounds has been confirmed to provide single-compound cure in an in vivo model of chronic Chagas disease up to 180 days after infection. 

Efforts continued but were heavily impacted by the COVID-19 pandemic.