DESCRIPTION (provided by applicant): Periodontitis represents a polymicrobial disease, in which a complex microbial ecology that matures in biofilms in the subgingival sulcus triggers a chronic immune-inflammatory lesion that destroys soft and hard tissues of the periodontium. Despite the great improvement in oral health in recent years, gingivitis and periodontal disease remain prominent and affect about half of all adults above the age of 30 years in the U.S., with an even higher prevalence in the underserved and developing and undeveloped countries. The ability to identify therapeutics, to enable more effective control and/or prevention of gingival inflammation, is a critical facet of current commercial strategies to improve oral health of the population. To address the unmet need for safe, cost-effective anti-gingivitis product/technology that promotes high patient compliance and could be incorporated into daily use, we have developed a novel, direct compression chewing gum formulation that contains freeze-dried blackberry powder (FBP) which is anti-inflammatory, antibacterial and antiviral. Our preliminary findings suggested this gum product is commercially viable and potentially effective for the prevention and/or treatment of gingivitis. The goal of this Phase II STTR proposal is to manufacture the chewing gum containing FBP that delivers bioactive phytochemicals to the oral cavity and test its efficacy in preventing biofilm formation and gingivitis in humans. Studies will determine the final gum product specifications and manufacturing method. A cGMP batch will be manufactured and Quality Control testing and Quality Assurance release will be performed. Submission and approval of an Investigational New Drug Application (IND) for an initial clinical study will be pursued based on guidance from our pre-IND meeting with FDA. In a randomized, double-blind, single center clinical efficacy study, we will assess the chewing gum's ability to reduce i) levels of several plaque-forming bacteria species on enamel and in saliva using the retrievable enamel chip model, and ii) clinical gingival inflammation, oral microbial burden and saliva biomarkers of inflammation in humans. These studies, if successful, will lead to a subsequent IND submission to complete multi-center trials and eventual NDA submission of the product for registration as a "Botanical Drug Product" as addressed under the FDA Guidance Document of the same title. Four Tigers LLC has partnered with WindStone Farms, the largest blackberry farm in the eastern part of the United States, to develop and commercialize health and medical products derived from blackberries. The investigators have assembled a highly interdisciplinary team encompassing collaborations between the agriculture industry, oral biologists, small business, and Tom's of Maine, a large healthcare company that focuses on all-natural products, that together will lead to the manufacture and commercial availability of an innovative blackberry chewing gum that releases and delivers natural bioactive substances from freeze-dried fruit powder that will help prevent/treat gingivitis.

This project presents the unique collaboration between the agriculture industry, oral biologists, small business, and a large healthcare company that will lead to the manufacture and commercial availability of an innovative blackberry chewing gum that releases and delivers natural bioactive substances from freeze-dried fruit powder that will help prevent/treat gingivitis. Use of this novel adjunctive oral hygiene aid could greatly reduce the cost of dental care by preventing oral disease before it occurs, and can be used by those who lack access to conventional oral hygiene measures.