Development of Novel Antifungal Drugs

Fungal diseases are a major and growing problem across the globe but unfortunately treatment options are limited. There are only four classes of drugs, and resistance to these is increasing. Our overall aim is to develop at least two preclinical drug candidates for cryptococcal meningoencephalitis, a major cause of death in immunocompromised people. We will prioritise broad-spectrum candidates, with differentiated mechanisms of action, that have activity against both Cryptococcus neoformans and Candida auris, a multi-drug resistant emerging fungal pathogen, and ideally also other fungi. C. neoformans is the highest priority pathogen on the WHO fungal priority list. We will be guided by Compound Progression Criteria based on Target Product Profiles and will apply both phenotypic and target-based approaches. Hit discovery will initially focus on C. neoformans, while we develop the screening cascade for C. auris. Any hits will be screened against a panel of other fungal pathogens from the WHO priority list. The compound optimisation process will be guided by AI-directed computational drug discovery, using physiologically-relevant cellular and animal models of disease. Mode of action studies will be integral to this work, to identify novel antifungal drug targets, to target-enable phenotypic series and to support portfolio management.