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: 10668735
• 负责人: Gary Fujii
• 金额: $ 6.72万
• 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: 2021-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10668735
• 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.

项目摘要/摘要 早产婴儿的表面活性剂缺乏会导致新生儿呼吸窘迫综合征（NRDS）。 NRDS 直接引起死亡率和发病率。 NRD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。 NRD的负担是保守的 估计占所有活产的1％，或全球140万新生儿，据报道未经治疗的NRDS病例死亡 低收入国家和中等收入国家的57％至89％。虽然动物衍生的表面活性剂用于治疗NRD 在1980年代开发的早产婴儿发病率和死亡率大大降低，不到三分之一 过早的婴儿接受表面活性剂治疗（基于表面活性剂销售）。成本限制和缺乏供应 是为什么未处理其余三分之二的主要因素。为了满足这种需求，分子表达， Inc.建议完成ME-101的后期开发和临床前活动，这是一项研究 肺表面活性剂由超级微型B肽组成，该蛋白质B，蛋白质成分模仿表面活性剂蛋白B 主要负责肺表面活性剂活性以及天然人肺的三高脂质 表面活性剂。 ME -101是一种完全合成的肺表面活性剂 - 即，它不受供应的限制 衍生产品，并具有一致的活动，产品均匀性，具有显着的优势， 以及当前销售动物和合成肺表面活性剂的制造业经济。主要目的 该直接到相的II SBIR应用程序是为制造商业可行的过程和 ME-101的质量控制，实施质量管理系统，生产和发布CGMP很多我 - 101，进行独立的活动，并组织，安排和进行与FDA的预定会议 在临床研究上获得最终一致性，以证明安全性，耐受性和功效。成功执行 这些目的将推动其发展的合成肺表面活性剂，并具有商业吸引力 与其他合成表面活性剂相比，活动和制造经济中的优势。消费者的成本降低 可能会转化为NRDS的表面活性剂治疗，并可能使用其他适应症 从而对改善全球公共卫生产生重大影响。