Development of Novel Therapeutics for HPV-related Precancer

Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 3-5 Budget (total costs, per award): Phase I: up to $400,000 for up to 12 months Phase II: up to $2,250,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary There is no effective medical therapy for the millions of men and women who are infected with human papillomavirus (HPV). HPV can result in cancers at several organ sites (e.g., cervical, anogenital, and oropharyngeal). The lack of approved non-surgical approaches for the treatment of HPV-related precancer is a significant unmet medical need. Current strategies for persistent HPV infections with no clinically actionable disease include periodic follow-up for viral clearance, which is burdensome, and can cause patients anxiety and stigmatization. If HPV-related cervical preneoplasia is present, current standard of care includes surgical excisional or ablative approaches that are associated with higher risk of preterm delivery, chronic pelvic and perineal pain, and anogenital disfigurement and morbidity, and require highly trained providers. Additionally, current strategies for HPV-related anal cancer include ablative and surgical approaches that have high morbidity, and there are no identifiable precancerous lesions to intervene for oropharyngeal cancers. Furthermore, these strategies are challenging to scale-up in lower resource settings due to lack of trained providers. Thus, novel systemic or topical/local approaches that intercept the progression of chronic HPV infection to precancer and/or induce regression of precancerous lesions can expand current therapeutic approaches and provide a precision prevention approach for HPVrelated cancers before tumors develop.