Development of a multispecies live biotherapeutic product for the prevention of recurrent bacterial vaginosis

Abstract Recurrent bacterial vaginosis (rBV) is the most common vaginal disorder among women of reproductive age and is caused by a loss of protective Lactobacillus bacteria and overgrowth of harmful bacteria (i.e. vaginal microbiota dysbiosis). While antibiotics can treat BV, they do not solve the underlying dysbiosis that contributes to the high rate of 50% recurrence within one year. Recurrent BV is associated with increased risk for a myriad of serious health complications, including STIs, HIV, and adverse pregnancy outcomes. Surprisingly, there are no approved therapies for preventing rBV. To address this unmet need in women’s health, we will build a live biotherapeutic product (LBP), STMC-105, a multispecies vaginal bacteria therapy designed to enhance durable Lactobacillus colonization and prevent rBV. STMC-105 will combine multiple protective Lactobacillus species (L. crispatus, L. gasseri, and L. jensenii) to support synergistic functionality and to address population diversity. We will take a systematic approach by selecting high-performing strains based on their potential to adhere to mucosal surfaces, reduce the burden of opportunistic organisms, metabolically cross-feeding on vaginal carbohydrates (SA1.1), and reduce vaginal cell inflammation (SA1.2). After optimal Lactobacillus strain selection, we will develop coculture conditions to prime cells for vaginal carbohydrate cross-feeding (SA2.1) and formulate live cells into a mucoadhesive extended- release vaginal tablet (SA2.2) to enhance vaginal colonization and potential to mitigate rBV. These developments will provide the foundation for clinical validation preparations (SA3.1) and support regulatory submissions (SA3.2) to evaluate the safety and efficacy of STMC-105 in a first-in-human clinical trial. The ultimate goal of this work is to develop an FDA approved LBP for the prevention of rBV. Such a product proven to be safe and efficacious would alleviate a significant gap in women's health and improve long-term outcomes for millions of people.