Symbiotic-based discovery for a safe selective antifungal therapy

Project Summary Antimicrobial innovation has slowed to a crawl while an epidemic of antimicrobial resistant infections surgesthreatening the public healthThe overarching goal of this project is to develop a novel natural product antifungalselvamicintargeting drug resistant fungal infectionsThis molecule was identified from a symbiotic animal environmentGrowing evidence suggests this is a rich and untapped source of novel compoundsMore importantlythe molecules from these symbiotic environments exhibit an extremely high rate of both biological activity and animal safetypresumably due to the evolutionary selection of the symbiotic relationship between the antibiotic producing microbe and animalConsistent with this hypothesispreliminary data with selvamicin demonstrates promising broad spectrum activity against drug resistant fungi in vitro and in pilot animal studies coupled with the absence of a toxicity signal from early cell and whole animal drug exposure studiesThe proposed Phasestudies will further explore the feasibility for clinical development of this lead antifungal via three IND enabling aimsAimsandwill expand preclinical efficacypharmacokineticand toxicology investigationAimwill focus on scale up compound production and physiochemical characterization needed for subsequent GLP production required for Phasetoxicology analysis and early human studiesThe milestones for success will clearly discern the therapeutic potential of selvamicin by defining the the murine PK PD target in standard FDA utilized modelsthe safety and therapeutic window for standard end organsand advance production and chemical analysis toward GLP GMP capacity for Phasedevelopment Relevance There are no effective therapies for the emerging resistant fungal pathogens that are becoming an increasing threat to the public healthThe goals of this Phaseproject are to further develop a drug from a promising new antifungal class to address this unmet clinical need for growing immunocompromised patient populations