Ronomilast: PDE4 inhibitor for chronic inflammatory disorders

Ronomilast (formerly ELB353) is a small molecule, potentially best-in-class phosphodiesterase-4 inhibitor (PDE4) in development for the treatment of chronic obstructive pulmonary disease (COPD).  Data from pre-clinical and early clinical trials indicates that the product has a good safety profile, and appears to be devoid of the gastrointestinal side effects that have typically impacted this class of drugs.  We are in the process of planning a Phase 2 trial in COPD patients and, given the nature and size of this indication, will also seek a partner for late-stage development of ronomilast.

About chronic obstructive pulmonary disease

COPD is a progressive, debilitating respiratory condition that restricts a person’s ability to breathe. COPD is characterized by two major contributing factors: emphysema and chronic bronchitis. In emphysema, the walls between the air sacs in the lungs are damaged, which reduces the amount of lung available for vital oxygen exchange. Chronic bronchitis on the other hand is characterized by irritation and inflammation of the lining of the airways, causing mucus formation and restriction of airflow. Both conditions are thought to be caused by heightened inflammation and can lead to reduced lung function and ultimately to death. According to The World Health Organization, COPD is the fourth most common cause of death; the global prevalence of COPD is rising rapidly and is estimated to affect 80 million people worldwide. The leading cause of COPD is cigarette smoking, although long-term exposure to other lung irritants, such as air pollution, chemical fumes, or dust, may contribute to the disease. There is currently no cure for COPD, although patients are treated symptomatically with bronchodilators and steroids to improve lung function and reduce exacerbations.

Ronomilast product profile

Ronomilast is an oral PDE4 inhibitor that is being developed as a potential treatment for COPD, but that could also have therapeutic promise in other chronic inflammatory disorders. PDE4 has been validated as an important inflammatory signaling target in various pre-clinical and clinical trials.

We believe that ronomilast could be well suited for the early treatment of COPD, given its convenient oral, once-daily formulation and potential impact on the underlying mechanism of disease. Treating the disease early could help to protect existing, healthy lung tissue and prevent the persistent decline in lung function that is characteristic of this condition.

In pre-clinical studies, ronomilast was a potent disease modifier in COPD, asthma, psoriasis, atopic dermatitis, rhinitis, rheumatoid arthritis, and in cigarette smoke-induced lung inflammation in mice. Importantly, when compared in-vivo to PDE4 inhibitors that are currently in late stage development or on the market, ronomilast treatment was very well tolerated with respect to central nervous system and gastrointestinal side effects, which have been a significant development hurdle for PDE4 inhibitors until now.

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Updated August 8, 2011