Clinical Development of a Therapeutic Agent for COPD

描述（由申请方提供）：粘液分泌过多进入呼吸道是几种肺部疾病的主要促成因素，包括慢性肺病（COPD）、哮喘、囊性纤维化、过敏性鼻炎和支气管扩张。尽管具有明显的医学重要性，但目前还没有有效的治疗方法来控制这些疾病中的过度粘液分泌，并且几乎没有潜在的治疗靶点。我们发现一种叫做MARCKS的特殊蛋白质是粘液分泌途径中的关键分子。基于这一发现，BioMarck开发了一种新的肽BIO-11006，它可以抑制粘液分泌过多以及培养的人气道上皮细胞和各种啮齿动物模型中炎症介质的释放。BIO-11006是一种具有粘液分泌和炎症双重功能的抑制剂，是潜在治疗包括COPD在内的各种肺部疾病的理想药物。在SBIR赠款的资助下，BioMarck继续开展该项目，并于最近成功完成了一项积极的IND，在172名患有慢性支气管炎的COPD患者中进行了为期21天的概念验证2A期临床研究，其先导化合物BIO-11006。这项SBIR II期桥接补助申请将允许BioMarck在300名慢性支气管炎COPD患者中开展为期90天的2B期多中心、双盲、剂量选择的BIO-11006临床研究。拟议项目的成功完成将使BioMarck能够为最终的III期临床研究选择剂量水平。在世界范围内，COPD的社会和经济负担巨大。慢性阻塞性肺疾病，是第三个。导致全球500多万人死亡。尽管目前市场上有超过25种不同的药物，但患者和护理提供者迫切需要用于治疗COPD的有效药物。BIO- 11006通过减少多余的粘液和气道炎症，有可能成为有效治疗这一患者群体的一流药物。

DESCRIPTION (provided by applicant): Hypersecretion of mucus into the respiratory airways is a major contributing factor in several lung diseases, including chronic pulmonary disease (COPD), asthma, cystic fibrosis, allergic rhinitis, and bronchiectasis. Despite the obvious medical importance, there presently are no effective therapies to control excess mucus secretion in these diseases, and very few potential therapeutic targets. We discovered that a specific protein called MARCKS is a key molecule in the mucus secretary pathway. Based on this finding BioMarck developed a novel peptide, BIO-11006, which inhibited mucus hypersecretion as well as release of inflammatory mediators in human airway epithelial cells in culture and in various rodent models. BIO-11006, being a dual function inhibitor mucus secretion and inflammation, is an ideal drug to potentially treat various lung diseases including COPD. With funding from SBIR grants, BioMarck continued work on this project and has recently successfully completed, under an active IND, a 21-day proof-of-concept Phase 2A clinical study in 172 COPD patients suffering from chronic bronchitis with its lead compound BIO-11006. This SBIR Phase II Bridge grant application will allow BioMarck to undertake a 90-day Phase 2B multi center, double blind, dose selection clinical study with BIO-11006 with 300 COPD patients suffering from chronic bronchitis. A successful completion of the proposed project will allow BioMarck to select a dose level for the final Phase 3 clinical study. Worldwide the social and economic burden of COPD is enormous. COPD, being the 3th. leading cause of death, accounts for over 5 million deaths worldwide. Although there are more than 25 different drugs currently available in the market, the patients and the care providers are desperate for effective drugs for the treatment of COPD. BIO- 11006, by reducing both excess mucus and airway inflammation, has the potential to be a first in class drug to effectively treat this patien population.