Testing a male oral contraceptive targeting Eppin

测试针对 Eppin 的男性口服避孕药

• 批准号: 9463025
• 负责人: MICHAEL GENE ORAND
• 金额: $ 109.76万
• 依托单位: EPPIN PHARMA, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-21 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9463025
• 关键词: Adverse effects; Binding; Biological Assay; Blood Chemical Analysis; Categories; Cell membrane; Characteristics; Contraceptive Agents; Contraceptive methods; Data; Developed Countries; Developing Countries; Dose; Drug Kinetics; Drug Targeting; Epididymis; Family Planning; Fertility; Fertility Study; Formulation; Gel; Goals; Growth; Hour; Human; Implant; Infertility; Infusion procedures; Injections; Lead; Liquid substance; Male Condoms; Male Contraceptive Agents; Methods; Monitor; Monkeys; Oral; Oral Contraceptives; Oregon; Partner in relationship; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pharmacology; Pharmacology Study; Phase; Prevalence; Primates; Production; Proteins; Public Health; Rattus; Research; Research Proposals; Seminal fluid; Small Business Technology Transfer Research; Sperm Motility; Spermatogenesis; Surface; Tablets; Technology; Testing; Testis; Therapeutic; Therapeutic Agents; Tubal Ligation; United States; Vasectomy; Veterinarians; Woman; condoms; contraceptive target; design; hormonal contraception; male; meetings; men; nonhuman primate; phase 1 study; pill; pre-clinical; preclinical study; scale up; sperm cell; unintended pregnancy

The global contraceptives market was valued at $16.0 billion in 2011 and is expected to grow at a CAGR of 5.9% from 2013 to 2018, to reach an estimated value of $23.3 billion in 2018. The contraceptive market consists of short-term methods such as condoms and oral contraception, long-term methods including implants and IUDs, and permanent methods such as tubal ligations and vasectomies. Eppin Pharma's product has a unique set of characteristics, namely ease-of use, high efficacy, reversibility and no side-effects, that differentiates it favorably from all the other male contraceptive competitors. An important high impact driver of this market is the prevalence of unintended pregnancies. In the US, there are 3.1 million unintended pregnancies annually through inconsistent or non-use of contraception. Eppin Pharma will be competing in the short-term contraception market. The goal of EPPIN PHARMA INC is to develop a non- hormonal male contraceptive drug that targets the protein EPPIN, which is present on the human sperm surface. Unlike hormonal contraception which inhibits spermatogenesis our therapeutic agent, EP055, is present in epididymal fluid and binds to EPPIN on the surface of sperm. The target EPPIN is only present in the male; in testis, epididymis, and on sperm, thereby reducing non-specific binding concerns. The Specific Aims of this STTR Phase 2 proposal are designed to build on STTR phase 1 data and formulate our lead compound, EP055, as an oral male contraceptive that targets EPPIN. Our goal in this STTR phase II application is to collect sufficient pharmacology data to conduct a pre-IND meeting with the FDA. Specific aim 1 will scale up production of purified EP055 to support additional preclinical studies and optimize AlphaScreen assays for formulation products. Specific aim 2 will complete formulation studies with EP055 and create a test batch of tablets for preclinical pharmacology studies. Specific aim 3 will conduct a monkey contraception/fertility study for proof of principle. Specific aim 4 will conduct oral pharmacokinetics studies in rats and monkeys, using oral gavage in rats, oral dosing of tablets in monkeys and conduct dose-range studies for PK/PD assessment.

2011年全球避孕药市场价值为160亿美元，预计2013年至2018年将以5.9%的复合年增长率增长，2018年估计价值将达到233亿美元。避孕市场包括短期避孕方法，如避孕套和口服避孕药，长期避孕方法，包括植入物和宫内节育器，以及永久性避孕方法，如输卵管结扎和输精管切除术。Eppin Pharma的产品具有一系列独特的特点，即易于使用、高效、可逆和无副作用，这使其与所有其他男性避孕药竞争对手区别开来。这个市场的一个重要的高影响力驱动因素是意外怀孕的普遍性。在美国，每年有310万例意外怀孕是由于不一致或不使用避孕措施造成的。Eppin Pharma将在短期避孕市场上竞争。EPPIN PHARMA INC的目标是开发一种针对人类精子表面蛋白EPPIN的非激素男性避孕药。与抑制精子发生的激素避孕不同，我们的治疗剂EP 055存在于附睾液中，并与精子表面的EPPIN结合。靶向EPPIN仅存在于雄性中;睾丸、附睾和精子中，从而减少非特异性结合问题。该STTR第2阶段提案的具体目标旨在建立在STTR第1阶段数据的基础上，并将我们的先导化合物EP 055配制为针对EPPIN的口服男性避孕药。我们在STTR II期申请中的目标是收集足够的药理学数据，以便与FDA进行IND前会议。具体目标1将扩大纯化EP 055的生产，以支持额外的临床前研究，并优化制剂产品的AlphaScreen测定。具体目标2将完成EP 055的处方研究，并创建用于临床前药理学研究的片剂试验批次。具体目标3将进行猴避孕/生育力研究，以证明原理。具体目标4将在大鼠和猴中进行经口药代动力学研究，在大鼠中经口灌胃，在猴中经口给予片剂，并进行剂量范围研究以进行PK/PD评估。