Clinical Development a Therapeutic Agent for COPD

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，它可以抑制培养的人类气道上皮细胞和啮齿动物的粘液分泌过多 哮喘模型在SBIR第一阶段和第二阶段赠款的资助下，BioMarck继续进行该项目的工作，已经完成了抑制MARCKS的肽（BIO-11006）的GMP生产，并成功完成了BIO-11006的非临床安全性研究，以支持向FDA提交的研究性新药（IND）申请。如果获得资助，这项SBIR II期竞争继续资助申请将允许BioMarck向FDA提交IND，并在56名健康受试者中进行剂量递增、安慰剂对照、双盲1期临床试验。 志愿者被设计来评估BIO-11006的安全性和耐受性。随后将在一项多中心、双盲、安慰剂对照的2a期临床试验中，在184名COPD患者中测试BIO-11006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，实现BIO-11006的商业化。在世界范围内，COPD的社会和经济负担是巨大的。COPD是第四大死亡原因，每年在全世界造成超过300万人死亡。呼吸系统市场迫切需要治疗哮喘和COPD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.