Preclinical Development of Occidiofungin for Treatment of Oral and Dermal Candidiasis

Project Summary Occidiofungin is a cyclic nonribosomally synthesized antifungal peptide with submicromolar fungicidal activity against drug resistant fungi. Optimization of the production and isolation of occidiofungin from liquid cultures of this bacterium has been performed. Furthermore, detailed structural determination, spectrum of activity, toxicity, and efficacy studies have been performed on occidiofungin. Several benchmarks used to evaluate the development of a novel therapeutic have been met with occidiofungin. Occidiofungin is a potent antifungal against fluconazole and caspofungin-resistant Candida species. Occidiofungin triggers cell death by inducing apoptosis in yeast cells. Occidiofungin has minimal toxicity in mice and GLP rodent micronucleus test (MNT) demonstrated no genotoxicity. Additionally, occidiofungin was shown to be effective in treating systemic and vaginal yeast infections in mice. All these studies point to the need to further the preclinical development of this novel compound. Occidiofungin, along with very few antifungal compounds, has met any of these benchmarks, and therefore it holds promise as a potential antifungal therapeutic agent for the treatment of several fungal diseases. IND enabling studies for an antifungal drug product to treat recurrent vulvovaginal yeast infections have been completed. The goal of this application is to develop products for the treatment of drug resistant or recurrent oral candidiasis (OC) and dermal candidiasis (DC). Establishing an effective formulation is required before the toxicological and stability studies are performed as outlined in this proposal. If the outlined studies prove to be successful, Sano Chemicals will file an IND application for an occidiofungin based treatment for OC and DC infections.