NOFUN · Novel antifungals to treat resistant organisms

Invasive fungal diseases are estimated to kill 1.5 million people each year. The incidence of mortality has risen significantly across the EU over the last 20 years due to an expansion of at risk patient populations. Given the obvious importance of these diseases it is perhaps surprising that only four classes of drug are available to treat systemic fungal infection. The azole class of antifungals provide the front line role for most disease treatment but recently resistance has emerged and it is of growing concern that levels are rising dramatically. European researchers have led the world in identifying the extent of the problem with some centres reporting itraconazole resistance in the Aspergillus species as high as 20% and in Candida, resistance to posaconazole upto 30%. Additionally the epidemiology of serious fungal infections is changing with more intrinsically resistant organisms now being seen more frequently. This represents a major problem for clinicians who are increasingly treating infections for which there is no current effective therapy.This proposal brings together leading European SME’s and academics to address this problem through the development of novel classes of antifungals and the identification of novel drug targets. The NOFUN consortium has identified potent novel broad spectrum antifungal molecules that are active against multi-resistant fungal pathogens and intends to qualify these as drug candidates. One of these assets is already at the lead identification stage. Cutting edge fungal genomics will be used to identify novel druggable targets and advance these to develop qualified tractable chemical inhibitors. With its wide ranging expertise across medicinal chemistry, ADMET, fungal biology, chemical genomics and drug development the partners will build and progress a broad pipeline of agents that have the potential to reach the clinic within 5 years.