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 这个项目的总体目标是在第一阶段SBIR研究的成功基础上再接再厉，以 进展NH101：结合DryNeb™的纯净(整齐)的两性霉素B干粉， 一种新型干粉喷雾器，可供临床使用。该计划的结果将使 第一阶段临床研究(AUS)，与FDA就NH101 505(B)(2)法规进行合作 批准途径，最终，研究新药(IND)申请和第二阶段 过敏性支气管肺曲霉病(ABPA)的临床概念验证(POC)疗效测试。 NH101(AMB-DryNeb™)通过针对常见和 曲霉菌的三唑(抗真菌类，如伊曲康唑)多药耐药(MDR)菌株 肺部感染的部位。NH101最初将专注于囊性纤维化(CF)和哮喘相关疾病 ABPA是一种罕见的、孤儿和严重的疾病，其医疗需求未得到满足，通常与 估计2.5%的哮喘患者(~500万)和15%(~20000)的CF患者。这个项目将 实现三个主要目标：1)将DryNeb™提炼、测试并生产到临床级规模， 2)放大并以千克规模配制AMB，以及3)首次实现人体可重复剂量 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.