Preparation and submission of an IND for PPCM Gel contraceptive

PROJECT SUMMARY Polyphenylene carboxymethylene sodium salt (PPCM) is being developed by Yaso Therapeutics as a woman-controlled, on-demand vaginal contraceptive gel (PPCM-GEL) with a unique, non-cytotoxic mechanism that triggers premature acrosomal loss of sperm, rendering them incapable of fertilization. Since PPCM also binds highly conserved glycosaminoglycans, this novel gel has additional potential to function as a multipurpose prevention technology (MPT) that protects against important bacterial and viral sexually transmitted infections (STIs). Under this grant we propose to complete one last packaging compatibility and stability study of PPCM-GEL, complete writing the IND per eCTD and FDA guidelines, and have a regulatory consulting firm electronically submit the IND to FDA. With the support of prior NIAID and NICHD grants (R42AI069659, R43/44AI084225,5R44HD092206), we have advanced PPCM through preclinical evaluation and have successfully formulated a mucoadhesive, non- irritating vaginal gel that is ready for clinical evaluation. The mechanism of action on sperm has enabled us to conduct pre-clinical studies using a commercially available sperm quality biomarker, hyaluronan binding assay (HBA®) to assess potential contraceptive activity. In pre-clinical testing, we have also demonstrated potent activity against Neisseria gonorrhoeae, herpes simplex virus, and HIV. PPCM-GEL is formulated for non- systemic topical use, is non-hormonal, and has potential to be one of the first successful MPT products with contraceptive and broad STI/HIV prevention efficacies. The prevalence of unplanned pregnancy and STIs among women in all economic, social, and cultural circumstances has remained high despite existing prevention options. There is a long-standing paucity of available on-demand and nonhormonal broad-spectrum prevention options. Availability of a dual-purpose product for contraception and STI/HIV prevention will arm people with an important option for reproductive health.