Non-clinical Development of a Synthetic Lung Surfactant for Treatment of NRDS

用于治疗 NRDS 的合成肺表面活性剂的非临床开发

• 批准号: 10432112
• 负责人: Gary Fujii
• 金额: $ 103.18万
• 依托单位: MOLECULAR EXPRESS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-18 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10432112
• 关键词: 37 weeks gestation; Advanced Development; Animals; Applications Grants; Biological Assay; Bronchopulmonary Dysplasia; Businesses; Case Study; Cause of Death; Cessation of life; Chemical Surfactants; Child; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Cyclic GMP; Development; Equipment; FDA approved; Facility Construction; Guidelines; Human; Human Resources; Incidence; Infant; Investigation; Life; Lipids; Live Birth; Methods; Molecular; Morbidity - disease rate; Neonatal Respiratory Distress; Nosocomial Infections; Oryctolagus cuniculus; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Pregnancy; Premature Birth; Premature Infant; Procedures; Proteins; Public Health; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactants; Qualifying; Quality Control; Research; Risk; Safety; Sales; Schedule; Secure; Small Business Innovation Research Grant; Source; System; Training; Translating; analytical method; base; cost; cost effective; improved; infant morbidity/mortality; intraventricular hemorrhage; low and middle-income countries; manufacturing process; meetings; mortality; neonate; peptide B; peptidomimetics; pre-clinical; preclinical development; premature; preterm newborn; public health relevance; respiratory; surfactant; surfactant deficiency

Project Summary/Abstract Surfactant deficiency in preterm infants causes the neonatal respiratory distress syndrome (NRDS). NRDS directly causes mortality and morbidity. NRDS also increases the risk of intraventricular hemorrhage, bronchopulmonary dysplasia, and nosocomial infections. The burden of NRDS has been conservatively estimated at 1% of all live births, or 1.4 million neonates globally, with a reported case fatality for untreated NRDS of 57 to 89% in low- and middle-income countries. Although animal-derived surfactants for treating NRDS developed in the 1980s greatly decreased preterm infant morbidity and mortality, fewer than one-third of premature infants receive surfactant treatment (based on surfactant sales). Cost constraints and lack of supply are primary factors for why the remaining two-thirds are not treated. To help fill this need, Molecular Express, Inc. proposes to complete the late stage development and preclinical activities for ME-101, an investigational lung surfactant comprised of the Super Mini-B peptide, which mimics Surfactant Protein B, the protein component primarily responsible for lung surfactant activity, as well as the three-major lipids of natural human lung surfactant. ME-101 is a fully synthetic lung surfactant - i.e., it is not limited by supply as is the case with animal derived products and has significant advantages in being well-defined with consistent activity, product uniformity, and economy of manufacturing over currently marketed animal and synthetic lung surfactants. The primary Aims of this Direct-to-Phase II SBIR application are to establish a commercially viable process for manufacturing and quality control of ME-101, implement a quality management system, produce and release a cGMP lot of ME- 101, perform IND enabling activities, and organize, schedule and conduct a Pre-IND meeting with the FDA to gain final alignment on the clinical studies to demonstrate safety, tolerability, and efficacy. Successful execution of these Aims will advance the development of a synthetic lung surfactant with commercial attractiveness due to advantages over other synthetic surfactants in activity and manufacturing economy. Reduced cost to consumers can potentially translate into broadened surfactant treatment of NRDS and potentially other indications for use thus exerting a significant impact on improving global public health.

项目总结/摘要 早产儿表面活性物质缺乏可引起新生儿呼吸窘迫综合征（NRDS）。NRDS 直接导致死亡和发病。NRDS还增加了脑室内出血的风险， 支气管肺发育不良和医院感染。NRDS的负担一直是保守的 估计占所有活产婴儿的1%，或全球140万新生儿，报告了未经治疗的NRDS的病例死亡率 在低收入和中等收入国家，这一比例为57%至89%。尽管用于治疗NRDS的动物源性表面活性剂 在20世纪80年代开发的早产儿预防措施大大降低了早产儿的发病率和死亡率， 早产儿接受表面活性剂治疗（基于表面活性剂销售）。成本限制和供应不足 是导致剩下的三分之二没有得到治疗的主要因素。为了满足这一需求，分子快递， Inc.建议完成ME-101的后期开发和临床前活动， 肺表面活性物质，由超级迷你-B肽组成，其模拟表面活性蛋白B（蛋白质组分） 主要负责肺表面活性剂活性，以及天然人肺的三种主要脂质 表面活性ME-101是一种完全合成的肺表面活性剂，它不像动物那样受到供应的限制， 衍生的产品，并具有显著的优势，在明确界定与一致的活动，产品的一致性， 和生产经济性。主要目标 该直接进入第二阶段SBIR申请的目的是建立一种商业上可行的生产工艺， ME-101的质量控制，实施质量管理体系，生产和放行cGMP批次的ME- 101、开展IND启动活动，并与FDA组织、安排和开展IND前会议， 获得临床研究的最终一致性，以证明安全性、耐受性和有效性。成功执行 这些目标将促进具有商业吸引力的合成肺表面活性剂的开发， 在活性和生产经济性方面优于其它合成表面活性剂。降低消费者的成本 可能转化为NRDS的更广泛的表面活性剂治疗，并可能转化为其他适应症 对改善全球公共卫生产生重大影响。