A novel, intravaginal prebiotic-gel (“PreBioGyn”) is proposed for cervical cancer prevention, through optimization of vaginal health and treatment of vaginal dysbiosis (pathogen and pathobiont overgrowth ), related to high-risk human papillomavirus (hrHPV) persistence and oncogenesis. PreBioGyn is an OTC user-directed, Class 2 medical device, uniquely innovative for women in Low Resource Settings (LRS), at greatest risk of death from cervical cancer. Increased rates of hrHPV persistence and cervical cancer are directly and indirectly linked to vaginal dysbiosis, due to elevations in vaginal pH levels, depletion of beneficial vaginal microbiota (e.g. Lactobacillus crispatus), and disruption of the mucosal barrier. Cervicitis and reduced vaginal acidity are leading risk factors for cervical cancer formation and progression. There is a significant need for an affordable, easy-to use vaginal product that optimizes vaginal pH, microbiota and mucosal function, to prevent cervical cancer . Existing vaginal pH “correcting” buffer-gels lower pH, but harm Lactobacillus and mucosal cells and/or don’t conform to WHO guidelines for vaginal safety. This is of critical public health significance given that ~90% of women report use of at least one vaginal product in any past 90 days, with use of such products increasing urogenital events (e.g. vaginal dysbiosis) 3-fold. In fact, a significant overlap occurs between women with high vaginal product use, hrHPV persistence and cervical cancer incidence, due, in part, to product-related vaginal microbiome and mucosa damage. Preliminary data show that the PreBioGyn patent-pending gel, with a novel prebiotic ingredient combination, supports L. crispatus while suppressing cervical cancer-linked P. bivia growth and is unparalleled in mucosal safety. Glyciome and academic partners (Brigham &Women’s Hospital and Univ of Puerto Rico School of Medicine) propose Phase 1 STTR studies to establish preclinical safety, efficacy and feasibility of the prebiotic gel and novel applicator (low-waste and shipping cost, enhanced user-ease and comfort). Successful completion of Phase 1 will demonstrate the following. 1) Vaginal biocompatibility of the gel in a physiologically relevant human in-vitro model vs leading buffer-gels, based on quantitative measures of: no cervicovaginal cell damage, inflammation and/or immunotoxicity; selective epithelial colonization by Lactobacilli; and no enhanced proliferation of pathobionts or cervical cancer cells. 2) User perception and acceptability of gel and applicator vs leading gels in quantifiable milestones of acceptance. 3) Physicochemical and functional properties of the gel over time and vs leading gels to demonstrate stability, and superior functionality and conformance with recommended guidelines. 4) Final design of an Integrated Manufacturing Prototype for coordination with the proposed manufacturer. Successful completion of the project will lead to STTR Phase 2 manufacturing scale up, clinical trials for optimization of vaginal health and prevention of cervical cancer, and filing for FDA device clearance with de novo vaginal health claims. Glyciome has assembled an expert team in: product development; manufacturing/sales; biostatistics; genital tract biology; and global cervical cancer care.

This STTR Phase 1 will establish preclinical safety, efficacy and feasibility of a patent-pending, prebiotic intravaginal gel, “PreBioGyn”, for OTC user-directed prevention of cervical cancer, by: i) optimizing vaginal pH, healthy bacteria and mucosal function ; and ii) reducing harmful (pathobiont) bacteria and human papillomavirus infections that increase cancer rates (especially in women from low-resource settings). The prebiotic activity of PreBioGyn, essential for supporting beneficial Lactobacilli, confers resistance to cervical cancer that is novel in comparison to existing vaginal products. Successful completion of this project will demonstrate preclinical biocompatibility of PreBioGyn in a human vaginal tissue model; high user acceptability of the device; and improved functionality and safety of PreBioGyn vs existing vaginal pH gels; as well as result in an integrated prototype for rapid commercial transition and profound benefit for reducing cervical cancer risk.