MucoCept-CVN, a genetically enhanced vaginal Lactobacillus strain for the prevention of HIV acquisition in women: Finalization of formulation for the first-in-human clinical trial

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Project Summary Half of new HIV infections occur in women as a result of unprotected vaginal intercourse with an infected partner. The cervicovaginal mucosa is the primary portal of entry for HIV in women. Women often cannot protect themselves due to imbalances in sexual relationships. The long-term goal of this project is to develop a safe and effective product to prevent HIV acquisition in women that is both female-controlled and coitally independent. To achieve this goal, we are developing a new approach that harnesses the protective properties of the vaginal microbiome to prevent infections. Protection is largely mediated by commensal Lactobacillus species that antagonize vaginal pathogens, including HIV, by producing lactic acid and other metabolites. MucoCept-CVN is a unique recombinant live biotherapeutic product (LBP) that contains a vaginal Lactobacillus jensenii strain that has been genetically enhanced to secrete a potent HIV entry inhibitor, modified cyanovirin-N (mCV-N). Colonization of the vaginal mucosa by this strain along with the continuous secretion of mCV-N is expected to reduce HIV acquisition in the female genital tract. The goal of this project is to complete the development of MucoCept-mCVN and satisfy FDA requirements to enable a Phase 1 clinical trial. An Investigational New Drug (IND) application was submitted to FDA for the MucoCept-CVN tablet formulation. Before clinical testing can proceed, FDA requested that we reformulate and retest the MucoCept-mCVN product in the rabbit vaginal irritation model (RVI) due to concerns about potential vaginal irritation by inactive tablet excipients. This SBIR II proposal describes the parallel development and preclinical testing of two new MucoCept-CVN formulations based on our experience with another vaginally administered LBP in advanced clinical development. This plan is designed to mitigate manufacturing and regulatory risks and to maximize the safety of the product in order to ensure FDA approval in the most time and cost efficient manner. Specifically, we will reformulate MucoCept-CVN tablet as a hydroxypropyl methylcellulose capsule and as a prefilled vaginal applicator using the same intermediate powder and manufacture small lots of the cGMP products for RVI and clinical testing. The two MucoCept-CVN formulations and placebos will be tested in the RVI model and compared to the vehicle control. The formulation with the lowest overall vaginal irritation potential will be selected for the clinical study. The IND will be amended to include the new safety and formulation information and submitted to FDA. Upon FDA approval, we will proceed with the first-in-human clinical study of this important product.