Preparation and submission of an IND for PPCM Gel contraceptive

项目总结 聚苯基羧亚甲基钠盐(PPCM)是由Yaso治疗公司开发的一种 女性控制的按需阴道避孕凝胶(PPCM-Gel)具有独特的、无细胞毒性的机制 这会触发精子的顶体过早丧失，使他们无法受精。由于PPCM还 结合高度保守的糖胺多聚糖，这种新型凝胶具有额外的潜在功能 多用途预防技术(MPT)，可在性方面防御重要的细菌和病毒 传播感染(STI)。在这笔赠款下，我们提议完成最后一项包装兼容性和 PPCM-Gel的稳定性研究，根据ECTD和FDA的指南完成IND的编写，并具有调节性 咨询公司以电子方式将IND提交给FDA。 在之前的NIAID和NICHD赠款(R42AI069659、R43/44AI084225、5R44HD092206)的支持下，我们已经 先进的PPCM通过临床前评估，并成功地配制了一种粘附性，非粘附性， 准备用于临床评估的刺激性阴道凝胶。对精子的作用机制使我们能够 使用可商业化的精子质量生物标记物透明质酸结合试验进行临床前研究 (HBA®)以评估潜在的避孕活动。在临床前测试中，我们也证明了有效的 抗淋病奈瑟氏菌、单纯疱疹病毒和艾滋病毒的活性。PPCM-GELL是为非 全身局部使用，是非激素的，有可能成为首批成功的MPT产品之一 避孕和广泛的性传播感染/艾滋病毒预防效果。计划外妊娠和性传播感染的流行情况 妇女在所有经济、社会和文化环境中的比例仍然很高，尽管存在 预防方案。长期以来，可用的按需和非荷尔蒙广谱药物很少。 预防方案。一种用于避孕和性传播感染/艾滋病毒预防的两用产品的供应将 对生殖健康有重要选择的人。

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.