SUPPORT FOR REGISTRATION ENABLING PHASE 3 CLINICAL TRIAL FOR NANOTECHNOLOGY-BASED TREATMENT OF CARCINOMA IN SITU OF THE ORAL CAVITY (STAGE 0 ORAL CANCER) - RFA-CA-22-025 APPLICATION ENTITLED "SUPPORT FOR REGISTRATION ENABLING PHASE 3 CLINICAL TRIAL FOR NANOTECHNOLOGY-BASED TREATMENT OF CARCINOMA IN SITU OF THE ORAL CAVITY (STAGE 0 ORAL CANCER)" PROJECT SUMMARY: ACCORDING TO THE AMERICAN CANCER SOCIETY, ABOUT 54,000 PEOPLE IN THE US WILL BE NEWLY DIAGNOSED WITH ORAL CANCER (OC) IN 2022, CAUSING 11,230 DEATHS. HISTORICALLY, OC HAS BEEN PRESENT IN HEAVY SMOKERS AND DRINKERS, HOWEVER OC HAS ALSO BECOME MORE PREVALENT IN YOUNGER POPULATIONS DUE TO HUMAN PAPILLOMAVIRUS (HPV). SURVIVORS MUST MANAGE DEVASTATING LIFELONG SIDE EFFECTS OF TREATMENTS WHICH CAN LEAD TO PERMANENT PSYCHOLOGICAL DAMAGE AND PHYSICAL DISFIGUREMENT. THE DIMINISHED QUALITY OF LIFE IS DUE TO THE PERMANENT PHYSICAL DISABILITIES RESULTING FROM SURGERY, THE FIRST-LINE TREATMENT REGARDLESS OF STAGE. THESE INCLUDE PERMANENT SPEECH IMPAIRMENT, AN INABILITY TO SWALLOW, AND/OR THE LOSS OF THE JAWBONE DUE TO THE SURGICAL REMOVAL OF THE TONGUE AND OTHER ORAL TISSUE. THE LONG-TERM COSTS ASSOCIATED WITH THE TREATMENT AND THESE DISABILITIES CAN RANGE FROM $100,000- $250,000, RESULTING IN ORAL CANCER PERSISTING AS ONE OF THE MOST EXPENSIVE OF ALL CANCERS TO TREAT. TO ADDRESS THIS UNMET NEED, PRIVO TECHNOLOGIES HAS DEVELOPED A TOPICAL CHEMOTHERAPY PATCH, PRV111, CAPABLE OF TRANSMUCOSAL DRUG DELIVERY THAT IS APPLIED DIRECTLY TO THE TUMOR. PRV111 CONSISTS OF A MUCOADHESIVE POLYMERIC PATCH WITH EMBEDDED CISPLATIN-LOADED NANOPARTICLES AND A NON-PERMEABLE BACKING THAT FACILITATES UNIDIRECTIONAL DRUG RELEASE, MAINTAINING LOCOREGIONAL CONTROL OF THE DRUG APPLICATION TO THE TUMOR SITE. CISPLATIN IS RECOGNIZED AS THE GOLD STANDARD CHEMOTHERAPEUTIC AGENT FOR TREATING ORAL CANCER, HOWEVER ITS EFFICACY IS OFTEN HINDERED BY SIGNIFICANT SYSTEMIC TOXICITY RESULTING FROM TRADITIONAL SYSTEMIC INTRAVENOUS (IV) ADMINISTRATION. PRV111 CAPITALIZES ON CISPLATIN'S CYTOTOXICITY, WITHOUT SYSTEMIC SIDE EFFECTS, THROUGH THE LOCALIZED DELIVERY. THE PRV111 NANOPARTICLES ARE OPTIMIZED TO ENSURE THAT CISPLATIN IS LOCALLY RETAINED WITHIN THE TUMOR TISSUE AND NOT EXPOSED TO SYSTEMIC BODILY CIRCULATION. PRV111 HAS BEEN INVESTIGATED IN A PHASE 1/2 TRIAL IN PATIENTS WITH EARLY-STAGE OC. THE TRIAL MET ALL SAFETY AND EFFICACY PRIMARY ENDPOINTS, WITH PRV111 HAVING AN 87% OVERALL RESPONSE RATE WITH AN AVERAGE TUMOR REDUCTION OF 70% IN 5.5 DAYS OF TREATMENT AND LABS DEMONSTRATING NO CISPLATIN IN PATIENT BLOOD. THE GOAL OF THIS PROPOSAL IS TO SUPPORT THE SUCCESSFUL COMPLETION OF PRIVO'S PHASE 3 CLINICAL TRIAL IN STAGE 0 OC/CARCINOMA IN SITU (CIS). THE GOAL OF THIS TRIAL IS TO ELIMINATE THE NEED FOR STANDARD OF CARE SURGICAL RESECTION BY OFFERING PRV111 AS A CHEMOABLATIVE ALTERNATIVE. SURGERY FOR CIS CARRIES HIGH DEGREES OF FUNCTIONAL AND COSMETIC MORBIDITY, AS THESE TUMORS ARE OFTEN SHALLOW AND WIDESPREAD NECESSITATING LARGE AMOUNT OF TISSUE TO BE REMOVED. DATA FROM THE PREVIOUS CLINICAL TRIAL DEMONSTRATED THAT PRV111 WAS ABLE TO CHEMOABLATE THE EPITHELIUM IN ALL TREATED PATIENTS, SO THE COMPANY IS CONFIDENT THAT CIS CAN BE ELIMINATED. THE SUCCESS OF THE PHASE 3 CLINICAL TRIAL WOULD POSITION PRIVO AND THE PRV PLATFORM TO BE SUSTAINED THROUGH REVENUE STREAMS FROM THE APPROVED PRV111, FOLLOWED BY SUPPLEMENTAL NDA SUBMISSIONS AND LABEL EXPANSION INTO FURTHER INDICATIONS. PRIVO'S TEAM OF SCIENTISTS, BUSINESS LEADERS, AND COLLABORATORS CAN EXECUTE ITS DEFINED AIMS WITH MILESTONES AND DELIVERABLES.