IND-Enabling Development of a Small Molecule COVID Therapeutic

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The proposed Phase I SBIR will conduct IND-enabling studies to establish the pharmacokinetics (PK) and SARS-CoV-2 (CoV-2) antiviral efficacy of sangivamycin (Sang) in Golden Syrian hamsters. Sang is an adenosine nucleoside analog that we discovered to be a potent, dose- dependent inhibitor of CoV-2 during in vitro viral infectivity studies conducted at the NIAID- Integrated Research Facility (IRF) at Fort Detrick. Sang had significantly superior efficacy against multiple variants of CoV-2 compared with Remdesivir but Sang also was additive with Remdesivir when used in combination. CoV-2 is the causative agent of COVID-19, which was first documented in China in December 2019 and has since rapidly spread across the globe, leading the World Health Organization to declare a global pandemic on March 11, 2020. CoV-2 has infected greater than 600 million individuals worldwide with at least 6.4 million attributable deaths to date. OyaGen has held type B preIND meetings with the FDA (PIND 150794). Historically, Sang was safely tested in 88 human subjects during NCI cancer clinical trials but was abandoned due to its lack of efficacy against cancers in human subjects. In this Phase I SBIR OyaGen seeks to complete preclinical development of Sang as a therapeutic candidate for COVID-19 to facilitate an IND application to conduct appropriate clinical trials leading to regulatory approval and commercialization. In response to FDA guidance and comments to our preIND filing (150794) the goal of this proposal is to conduct PK of Sang in a hamster animal model (Aim 1) as well as to determine in vivo antiviral efficacy of Sang in the hamster COVID-19 model (Aim 2). The development of Sang as a therapeutic for infected patients is a medical countermeasure for immunocompromised people who may not benefit from immunization as well as a stop gap therapeutic for new strains of CoV for which current vaccines may be less effective. Importantly, our data support that Sang has the potential to enhance the efficacy of other therapeutics as a combination therapy option in the future.