Clinical Development of a Therapeutic Agent for COPD

描述(申请人提供)：粘液过度分泌到呼吸道是几种肺部疾病的主要致病因素，包括慢性肺部疾病(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的过度粘液分泌，而且几乎没有潜在的治疗靶点。我们发现，一种名为Marcks的特定蛋白质是粘液分泌途径中的关键分子。基于这一发现，BioMarck开发了一种新型多肽BIO-11006，它在培养的人呼吸道上皮细胞和各种啮齿动物模型中抑制粘液高分泌和炎性介质的释放。BIO-11006是一种粘液分泌和炎症的双重功能抑制剂，是潜在治疗包括慢性阻塞性肺疾病在内的各种肺部疾病的理想药物。在SBIR赠款的资助下，BioMarck继续这一项目的工作，最近在活跃的IND下，成功地完成了一项为期21天的概念验证第2A期临床研究，使用其先导化合物BIO-11006对172名患有慢性支气管炎的慢性阻塞性肺疾病患者进行了研究。这一申请将使BioMarck能够利用BIO-11006对300名慢性支气管炎慢性阻塞性肺疾病患者进行为期90天的多中心、双盲、剂量选择临床研究。拟议项目的成功完成将使BioMarck能够为最终的3期临床研究选择剂量水平。在世界范围内，慢性阻塞性肺病的社会和经济负担是巨大的。慢性阻塞性肺疾病，作为第三个。主要死因，在全世界造成500多万人死亡。尽管目前市场上有超过25种不同的药物可供选择，但患者和护理提供者迫切需要有效的药物来治疗COPD。BIO-11006通过减少多余的粘液和呼吸道炎症，有可能成为有效治疗这类患者的一流药物。

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.