Preparation and submission of an IND for PPCM Gel contraceptive

准备并提交 PPCM 避孕凝胶的 IND

• 批准号: 10483274
• 负责人: Mary B Weitzel
• 金额: $ 29.85万
• 依托单位: YASO THERAPEUTICS INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-06 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483274
• 关键词: AIDS prevention; Anti-Infective Agents; Binding; Biological Assay; Biological Markers; Clinical Trials; Collaborations; Consult; Contraceptive Agents; Contraceptive methods; Economics; Female; Fertilization; Gel; Glycosaminoglycans; Grant; Guidelines; HIV; Hyaluronan; Individual; National Institute of Allergy and Infectious Disease; National Institute of Child Health and Human Development; Neisseria gonorrhoeae; No-Observed-Adverse-Effect Level; Oral Administration; Oryctolagus cuniculus; Pamphlets; Persons; Pharmacologic Substance; Phase; Phase I Clinical Trials; Preclinical Testing; Preparation; Prevalence; Prevention; Protocols documentation; Rattus; Reproductive Health; Research Personnel; Safety; Sexually Transmitted Diseases; Simplexvirus; Small Business Innovation Research Grant; Sodium; Sodium Chloride; Technology; Therapeutic; Toxicology; Universities; Vagina; Vaginal Gel; Vaginal Route of Drug Administration; Viral; Viral Sexually Transmitted Diseases; Woman; Writing; antimicrobial; arm; effectiveness testing; external genitalia; first-in-human; male; meetings; men; novel; penis; preclinical evaluation; preclinical study; premature; research and development; research clinical testing; social; sperm cell; sperm quality; unintended pregnancy

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.

项目摘要 聚亚苯基羧基亚甲基钠盐（PPCM）由Yaso Therapeutics开发， 女性控制、按需阴道避孕凝胶（PPCM-GEL）具有独特的非细胞毒性机制 引发精子顶体过早丢失，使其无法受精。由于PPCM还 结合高度保守的糖胺聚糖，这种新型凝胶具有额外的潜力，作为一种 多用途预防技术（MPT），保护免受重要的细菌和病毒性 传播感染（STI）。根据这项资助，我们建议完成最后一次包装兼容性， PPCM-GEL的稳定性研究，根据eCTD和FDA指南完成IND的撰写，并进行监管 咨询公司以电子方式向FDA提交IND。 在先前NIAID和NICHD赠款（R42 AI 069659，R43/44 AI 084225，5 R44 HD 092206）的支持下，我们 通过临床前评估先进的PPCM，并成功配制了一种非粘膜粘附剂 刺激性阴道凝胶，准备进行临床评估。对精子的作用机制使我们能够 使用市售精子质量生物标志物透明质酸结合试验进行临床前研究 (HBA（5）评估潜在的避孕活性。在临床前测试中，我们也证明了 抗淋病奈瑟菌、单纯疱疹病毒和HIV的活性。PPCM-凝胶是制定为非 全身局部使用，是非激素，并有可能成为第一个成功的MPT产品之一， 避孕和广泛的性传播感染/艾滋病毒预防功效。意外怀孕和性传播感染的流行率 妇女在所有经济、社会和文化环境中的比例仍然很高， 预防选择。长期以来，按需和非激素类广谱药物缺乏， 预防选择。避孕和性传播感染/艾滋病毒预防两用产品的提供将使 对生殖健康有重要选择的人。