Funding Opportunity Number: RFA-AI-24-065
Deadline: January 28, 2025
Background
Invasive fungal infections (IFIs) are significant causes of morbidity and mortality worldwide, leading to an estimated one and a half million deaths per year. Only three major classes of antifungals are in use clinically and the treatment of IFIs remains challenging due to limited options, toxicities, drug-drug interactions, restricted routes of administration, limited central nervous system (CNS) penetration, and emerging resistance. Despite increased emphasis on development of new drugs and therapeutic approaches to augment clinical options and combat antimicrobial resistance, the discovery and development of novel therapeutics against fungal pathogens largely fall behind that for other pathogens. Advances of in vitro and in vivo assay development for fungal pathogens coupled with recent progress in understanding the molecular and genetic mechanisms that contribute to antifungal resistance offer unique opportunities for therapeutic target identification and therapeutic discovery for fungal pathogens. This initiative aims to advance antifungal development for pathogens highlighted on the NIAID Biodefense and Emerging Infectious Disease Pathogens webpage, and in the Centers for Disease Control and Prevention’s Antibiotic Resistance Threats report (2019) and The WHO fungal priority pathogen list (2022).
Research Objectives and Scope
This initiative will support research projects focused on discovery and development of novel therapeutics against select fungal pathogens of clinical concern. Applications must target at least one of the following priority fungal pathogens: Candida species, specifically Candida auris; Aspergillus fumigatus; Coccidioides; and Mucorales. A novel therapeutic is defined as an agent with a mechanism of action that differs from existing agents; an agent against a non-traditional target; an agent against a traditional target but with significantly improved safety and tissue distribution; or an agent that can circumvent known resistance mechanisms associated with a traditional target. It is anticipated that this initiative will provide additional and improved therapeutic starting points and accelerate preclinical development of candidates.
Examples of potential approaches to be supported include, but are not limited to:
- Discovery and validation of novel fungal pathogen-specific or host-specific therapeutic targets using synthetic disease models or animal models. Exploitation of targets common to yeasts, dimorphic fungi and molds is strongly encouraged.
- Identification and/or development of novel compounds that circumvent resistance mechanisms.
- Identification and/or development of novel compounds with broad-spectrum activity against select fungal pathogens.
- Characterization/down-selection of novel compounds and/or preclinical development of lead candidates.
For more information, please see the opportunity webpage.