Development of NH101: A Simple and Efficient Outpatient Dry Powder Amphotericin B-DryNeb(dry powder nebulizer) for Treatment of Susceptible and Multidrug Resistant Aspergillus/ Fungal Infections

项目摘要 本项目的总体目标是在第一阶段SBIR研究的成功基础上， Progress NH 101：与DryNe B ™组合的阿替霉素B（AMB）的纯（纯）干粉， 一种新型的干粉雾化器进入“临床就绪”状态。该计划的结果将使一个 I期临床研究（AUS），与FDA就NH 101 505（B）（2）监管进行合作 批准途径，最终，研究性新药（IND）申请和II期 过敏性支气管肺炎（ABPA）的临床概念验证（POC）有效性试验。 NH 101（AMB-DryNeb™）通过针对常见的和未满足的医疗需求， 三唑（抗真菌类，例如，伊曲康唑）多药耐药（MDR）曲霉菌株 肺部感染的部位。NH 101最初将专注于囊性纤维化（CF）和哮喘相关性 ABPA是一种罕见的孤儿和严重疾病，通常与未满足的医疗需求相关， 估计2.5%的哮喘患者（约500万）和15%的CF患者（约20，000）。该项目将 实现三个主要目标：1）将DryNeb™提炼、测试和生产到临床级规模， 2)按比例放大并以Kg规模配制AMB，以及3）首次在人体内进行使能重复剂量 GLP毒理学研究。

Project Summary The overall objective of this project is to build on the successes of our Phase I SBIR studies to progress NH101: a pure (neat) dry powder of amphotericin B (AMB) combined with the DryNeb™, a novel dry powder nebulizer to “clinic ready” status. The results of this program will enable a Phase I clinical study (AUS), engagement with the FDA on the NH101 505(b)(2) regulatory approval pathway, and ultimately, an Investigational New Drug (IND) application and Phase II clinical proof of concept (POC) efficacy testing in Allergic Bronchopulmonary Aspergillosis (ABPA). NH101 (AMB-DryNeb™) satisfies multiple unmet medical needs by targeting common and triazole (antifungal classes, e.g., itraconazole) multidrug resistant (MDR) strains of aspergillus at the site of lung infection. NH101 will initially focus on cystic fibrosis (CF) and asthma-associated ABPA, a rare, orphan and severe disease of unmet medical need commonly associated with an estimated 2.5% of asthmatics (~5 million) and 15% (~20,000) of CF patients. This project will achieve three primary objectives: 1) refine, test, and produce the DryNeb™ to clinical-grade scale, 2) scale up and formulate AMB at Kg scale, and 3) perform a first in human-enabling repeat dose GLP toxicology study.