Preclinical Development of OCF001 for Treatment of Yeast Infections

Project Summary
Occidiofungins (A-D) are cyclic nonribosomally synthesized antifungal peptides with
submicromolar fungicidal activity against a broad spectrum of fungi. Optimization of the production
and isolation of occidiofungins from liquid cultures has been performed. The production and
isolation of predominantly one analog, called occidiofungin B (OCF001), supports its commercial
development as a novel antifungal therapeutic. Several of the benchmarks used to evaluate the
development of a novel therapeutic have been met with OCF001. OCF001 is a potent antifungal
against fluconazole and caspofungin-resistant Candida species. It was also shown to be effective
at inhibiting Candida auris at 0.25 g/ml. The antifungal triggers cell death by inducing apoptosis
in yeast cells and was shown to have minimal toxicity in mice dosed with 2 mg/kg in a 28-day
toxicity study. Furthermore, OCF001 was demonstrated to be an effective antifungal treatment for
vaginal yeast infections in mice. All these studies point to the need to further the preclinical
development of this novel compound. OCF001, along with very few antifungal compounds, have
met any of these benchmarks, and therefore it holds promise as a potential antifungal therapeutic
agent. The goal of this application is to complete the pre-Investigational New Drug (pre-IND)
enabling and IND enabling studies for the development of an antifungal product for the treatment
of systemic and vaginal yeast infections.Project Narrative
The proposal addresses the need for the development of novel broad-spectrum antifungal
products for vulvovaginal yeast and invasive yeast infections. The studies proposed are essential
for filing two Investigational New Drug Applications (INDAs).