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

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.