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Targeting fungal stress responses to provide first-in-class treatment for drug resistant fungal pathogens

Genomic Applications Partnership Program
GAPP Round: 
Genome Centre(s):
Ontario Genomics
Project Leader(s):
Leah Cowen (University of Toronto)
Receptor Leader(s):
Dominic Jaikaran (Bright Angel Therapeutics)
Fiscal Year Project Launched: 
Project Description: 

The impact of fungal infections on human health in Canada is profound, with recent epidemiological reports of approximately 3,000 invasive fungal infections annually, resulting in approximately 1,000 deaths, with immunocompromised individuals being the most vulnerable. Only three major classes of antifungal drugs are currently available and resistance to each class is increasing at an alarming rate. This team has established that fungal stress responses are critical for fungal drug resistance and virulence traits and has identified potential antifungal inhibitors of the molecular chaperone and stress response regulator Hsp90. This project couples Schrödinger’s computational drug discovery expertise with the Cowen lab’s expertise in fungal genomics and Hsp90 to enable Bright Angel Therapeutics to rapidly translate existing data supporting the benefit of targeting fungal Hsp90 into an IND-ready drug candidate. The project will pursue a 3-task development approach based on computational design, targeted medicinal chemistry, and biological verification/validation. The project gives Canada a chance to be a global leader in antifungal research. The drug coming to market would be expected to reduce morbidity and mortality due to fungal infections and provide significant savings to the Canadian health care system, which currently spends $345 million on invasive fungal infections.