ARRY-502, an oral CRTh2 antagonist, has the potential to be an effective treatment for patients with asthma, particularly those with severe conditions, and may have advantages over competitor molecules. In various preclinical models of allergic inflammation, ARRY-502 has demonstrated a high level of anti-inflammatory activity. In initial Phase I clinical trials ARRY-502 has been well tolerated and demonstrated pharmacodynamic activity.

Inappropriate inflammatory responses to environmental allergens underlie allergic reactions such as allergic asthma, allergic rhinitis and atopic dermatitis, which collectively affect up to 20% of the United States population. Despite the range of treatments used to treat allergic asthma, there remains a significant need for patients with severe asthma as well as for more convenient and safer therapies for those with mild to moderate asthma. Although severe asthma affects only approximately 10% of the asthmatic population, the condition results in approximately 60% of total healthcare costs associated with asthma. Currently, few treatment options exist for patients with severe asthma.

In severe allergic asthma, there is emerging evidence suggesting that a greater presence of the mediator prostaglandin D2, or PGD2, and an upregulation of CRTh2, a protein receptor for PGD2 that is expressed on inflammatory cells, may play a particularly important role in greater symptoms of asthma such as coughing and difficulty breathing and lower lung function. Indeed, activation of CRTh2 has been shown to result in chemotaxis and activation of inflammatory cells and stimulate the production of cytokines that are thought to drive asthma pathophysiology.

Based on the role of CRTh2 in mediating the actions of PGD2, selective antagonism of CRTh2 presents an attractive therapeutic approach to the treatment of severe allergic conditions. There are selective antagonists of CRTh2 in various stages of clinical development with compounds currently being evaluated in early Phase 2 studies in allergic rhinitis, asthma and eosinophilic esophagitis.

Array initiated a 14-day Phase 1, randomized, double blind, multiple ascending dose trial with ARRY-502 in healthy volunteers for the evaluation of safety, pharmacokinetics and pharmacodynamics. The results to date from the Phase 1 single ascending dose study indicate that ARRY-502 has been well-tolerated at the doses evaluated, has shown excellent exposure and demonstrated good activity in pharmacodynamic assessments. Array expects to initiate a 28-day Phase 2a trial in persistent asthma during fiscal 2011.