OX-CLI
The OX-CLI project is based on Orexo’s leading research in the arachidonic acid cascade. The objective of the project is to develop an oral, non-steroidal, anti-inflammatory and bronchodilatory drug for the treatment of all stages of asthma and COPD. The target protein in the OX-CLI project is the enzyme LTC4 synthase, which has a central role in the inflammatory process by acting as a catalyst in the final stage of formation of leukotrienes and eoxins, which are two groups of major pro-inflammatory mediators. Studies on mice that lack the LCT4 synthase have also shown a significant reduction in inflammatory responses in various models for respiratory tract disorders. The broad mechanisms of action indicate that a better therapeutic effect could be attained using an LCT4 synthase inhibitor rather than with current oral treatments using leukotriene inhibitors such as montelukast (Singulair®).
Project status
Orexo has identified series of proprietary molecules and established a patent portfolio of potential drug candidates. A number of these have shown good effects in various pharmacological animal models. Work is continuing in order to optimize biological effects and other characteristics that are important for an effective and safe drug.
Market
COPD is a very serious illness involving chronic inflammation in the respiratory tracts (frequently caused by smoking), which leads to the progressive and irreversible decrease in lung function. About 7–8 percent of the population is estimated to suffer from COPD in various stages. Asthma affects 6–8 percent of the adult population and some 10 percent of children.
Sales of drugs designed to treat diseases in the respiratory tracts, especially asthma and COPD, totaled USD 29bn in 2007, according to Business Insights’ September 2008 report entitled Innovations and Pipelines for Respiratory Disorders. Asthma patients are treated with inhaled bronchodilating ß2 agonists for fast relief and with inhaled corticosteroids for anti-inflammatory effect. Combination products with long-acting ß2 agonists and steroids are common. However, many would like to avoid steroids as they are viewed as entailing a risk of side effects, such as inhibited growth among children and bone decalcification. Patients with COPD are most often treated with the same drugs as asthma patients and with anticholinergic bronchodilating drugs developed specifically for COPD.