Kovina Therapeutics Inc. — Department of Health and Human Services SBIR Phase II: NCI

Description

ABSTRACT “High-risk” human papillomavirus (HPV) types such as 16 (HPV-16) are identified in the majority of HPV-associated pre-malignant and malignant pathologies of cervical, anogenital, and oropharyngeal epithelia. TheE6 protein is essential for viral replication. Structure-based computational screening followed by design andsynthesis of derivatives led to the identification of a series of small molecules that bind to the HPV-16 E6 protein and inhibits its association with the E6AP ubiquitin ligase in vitro as well as E6-mediated p53degradation in cells. Using iterative cycles of structure based drug design and rigorous biochemical assays,Kovina Therapeutics’ academic collaborators have identified more potent E6 inhibitory compounds. Kovinahas an exclusive worldwide license to these discoveries. The objective of this STTR application is to characterize the pharmacokinetic properties of these unique E6 inhibitors and identify the best candidates foradvancement as therapeutics. Specific inhibition of growth of HPV-16 xenograft tumors will serve as proof ofconcept validation for our lead candidates. We are ideally positioned to perform and complete requisitepharmacokinetic, pharmacologic and toxicologic studies in the SBIR phase, leading to IND-enabling selectionof a clinical lead. Having developed and executed the experiments described in this project, the PI, Dr. AnneRietz, is superbly suited to continue these investigations. She will be mentored by senior leaders fromacademia and the drug industry. Kovina’s CEO and Board Chair, who have successfully grown and managedtwo biotech companies that were acquired, will also mentor Dr. Rietz. Along with other mentoring venues andbusiness school courses, Dr. Rietz will transition to a career in corporate drug development.