Inspire Pharmaceuticals, Inc.

MUCOCILIARY CLEARANCE - The process by which mucosal surfaces such as the lungs and sinuses are cleared of particles such as dust, bacteria and viruses by the action of cilia. Cilia are small, hair-like projections that move in a waving motion to "sweep" debris away from the mucosal surface. The cilia are suspended in a layer of fluid, which allows them to move freely. Both the fluid layer and the movement (or beat) of the cilia are essential for the health of mucosal surfaces such as the lungs and sinuses.

Cystic fibrosis is a life-threatening disease involving a genetic mutation that moves salt and water to the surface of the lungs, providing hydration and cleansing of the lung's surface. In healthy individuals, this protein acts as an ion-specific channel that modulates salt and water movement. In cystic fibrosis patients, a defect in this channel leads to poorly hydrated, thickened mucous secretions in the airways, as well as severely impaired mucociliary clearance. Impairments in these vital lung defense mechanisms typically begin in early childhood. Chronic secondary infections invariably occur, resulting in progressive lung dysfunction and deterioration. Cystic fibrosis-induced damage to the respiratory tract accounts for more than 95% of the morbidity and mortality associated with this disease. According to the U.S. Cystic Fibrosis Foundation, the median life expectancy for patients is 35 years.

The current therapeutic approaches to address cystic fibrosis mainly treat the symptoms, but do not cure the disease, and are aimed at reducing respiratory infections and breaking up thickened mucous secretions that cause airflow obstruction and harbor bacteria. For example, TOBI^® is an inhaled antibiotic that treats the infection, and Pulmozyme^® is an inhaled protein that breaks up excessive DNA in mucus thereby reducing the thickness and tackiness of the respiratory secretions. While both products are approved for the treatment of cystic fibrosis, neither product is designed to address the underlying ion-transport defect, which results in dehydrated mucus and severely impaired mucociliary clearance. INS37217 Respiratory has the potential to intervene in the early course of CF lung disease, by activating an alternative ion channel that acts in the same way as the defective channel to move water and salt to the surface of the lungs.

There are approximately 30,000 diagnosed cystic fibrosis patients in the United States and approximately 75,000 in the eight major international prescription pharmaceutical markets.