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.
More than 200 million individuals worldwide suffer from COPD. As many as 14.8 million people were diagnosed with COPD (and an equal number of undiagnosed) in the U.S. during 2008-09 (NIH Morbidity and Mortality Chart Book, 2012). COPD is known to have caused 140,000 deaths in the U.S. during the same year, and is now the 3rd leading cause of death. The incidence of COPD around the world is rapidly increasing and is largely driven by an increase in the number of smokers and increasing air pollution. The World Health Organization estimates that 2.7 million people died of COPD worldwide in 2000. COPD is characterized by progressive destructive changes of airway and lung architecture that leads to limitations in airflow. These physiological changes lead to poorly reversible airway obstruction and impairment of gas exchange in the lungs. The most common clinical expression of COPD is a combination of chronic bronchitis and emphysema. Chronic cough, frequent clearing of the throat, wheezing, and shortness of breath after mild exertion are common symptoms. COPD is a slowly progressive, mostly irreversible disease characterized by a gradual loss of lung function. Hypersecretion of mucus into the lungs is a major contributing factor in several lung diseases, including COPD, asthma, and cystic fibrosis. Despite the obvious medical importance, there presently are no effective therapies to control excess mucus secretion in these diseases. We discovered that a specific protein called MARCKS is a key molecule in the mucus secretion. Based on this finding BioMarck is developing a novel compound, BIO-11006, as a potential new treatment for patients with COPD. With funding from SBIR, BioMarck has recently completed a proof-of-concept early clinical study of short duration in a small number of COPD patients. BioMarck intends to continue working on this project and to develop this potential drug to help needy COPD patients.