Development of Small Molecules with Antifungal Properties for Safe Use in Human Patients (Direct to Phase II)

The DHA26BZ01-DV005 initiative seeks Direct to Phase II proposals for developing small molecules with broad-spectrum antifungal properties for safe human use, aiming for FDA clearance. Fungal infections pose a significant global health challenge, particularly for immunocompromised individuals and the military, with current treatments limited by toxicity and drug resistance. The objective is to identify small molecules from existing libraries that exhibit fungicidal activity against key pathogens like Candida auris, Fusarium, Aspergillus, and Mucorales species at nanomolar concentrations, with a cytotoxicity profile similar to or better than Amphotericin B. Phase II will involve optimizing lead candidates into viable in vivo treatments, testing efficacy in organoid and small animal models, and demonstrating operational effectiveness with a minimum six-month shelf life in austere conditions. Phase III focuses on transitioning the technology for military and civilian use, securing FDA approval through large animal testing and clinical trials, and optimizing for a one-year shelf life in austere environments. The goal is to make the product accessible to both military and civilian users.