Clinical Development a Therapeutic Agent for COPD

粘液过度分泌进入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开发了一种新的多肽，它可以抑制培养的人呼吸道上皮细胞和啮齿动物的粘液高分泌 哮喘模型。在SBIR第一阶段和第二阶段拨款的资助下，BioMarck继续进行这一项目的工作，已经完成了抑制Marcks的多肽(BIO-11006)的GMP制造，并成功完成了BIO-11006的非临床安全性研究，以支持向美国食品和药物管理局提出的研究新药(IND)申请。如果获得资金，这项SBIR第二阶段竞争性继续拨款申请将允许BioMarck向FDA提交IND，并在56名健康患者中进行剂量递增、安慰剂对照、双盲的第一阶段临床试验 旨在评估BIO-11006安全性和耐受性的志愿者。随后将在多中心、双盲、安慰剂对照的2a期临床试验中测试BIO-11006对184名慢性阻塞性肺疾病患者的疗效和药效学。该项目如果成功，将通过与一家大型制药公司合作提供进一步扩大临床试验所需的数据，从而导致BIO-11006的商业化。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。慢性阻塞性肺病是第四大死因，每年在全球范围内造成300多万人死亡。呼吸系统市场急需治疗哮喘和慢性阻塞性肺病的有效药物。

Hypersecretion of mucus into the respiratory airways is a major contributing factor in several lung diseases, including chronic pulmonary disease (COPD), asthma, cystic fibrosis, 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, which inhibited mucus hypersecretion in human airway epithelial cells in culture and in a rodent model of asthma. With funding from SBIR Phase I and Phase II grants, BioMarck continued work on this project, has accomplished GMP manufacturing of a peptide (BIO-11006) that inhibits MARCKS, and successfully finished the nondinical safety studies of BIO-11006 in order to support an Investigational New Drug (IND) application to the FDA. This SBIR Phase II Competing Continuation grant application, if funded, will allow BioMarck to file an IND with FDA and conduct a dose-escalating, placebo-controlled, double-blind Phase 1 clinical trial in 56 healthy volunteers designed to evaluate the safety and tolerability of BIO-11006. This will be followed by testing BIO-11006 efficacy and pharmacodynamics in 184 COPD patients in a multi-center double-blind, placebo-controlled Phase 2a clinical trial. This project, if successful will lead to commercialization of BIO-11006 by providing data required for further expanded clinical trials in collaboration with a large pharmaceutical company. Worldwide, the sodal and economic burden of COPD is enormous. COPD, being the fourth leading cause of death, accounts for over 3 million deaths each year worldwide. The respiratory market is desperate for effective drugs for the treatment of asthma and COPD.