Bepotastine

We are developing bepotastine as a prescription pharmaceutical eye drop treatment for ocular allergy. Bepotastine has three primary mechanisms of action. It is a non- sedating, selective antagonist of the histamine 1 (H1) receptor, it has a stabilizing effect on mast cells, and it suppresses the migration of eosinophils into inflamed tissues. The compound’s primary mechanisms of action are believed to make it an effective treatment against the signs and symptoms of allergic conjunctivitis.

Bepotastine was approved in Japan for use in the treatment of allergic rhinitis and uriticaria/puritus in July 2000 and January 2002, respectively, and is marketed by Tanabe Seiyaku Co., Ltd. under the brand name TALION. TALION was co-developed by Tanabe Seiyaku and Ube Industries, Ltd., who discovered bepotastine. In 2001, Tanabe Seiyaku granted Senju exclusive worldwide rights, with the exception of certain Asian countries, to develop, manufacture and market bepotastine for ophthalmic use. In 2006, we acquired North American rights to bepotastine under a licensing agreement from Senju.

Clinical/Regulatory Status:
During the first quarter of 2007, we initiated a U.S. Phase II/III study of bepotastine ophthalmic solution for treatment of allergic conjunctivitis. This Phase II/III study was a single-center, double-masked, randomized, placebo-controlled evaluation in approximately 90 patients of the onset and duration of action of bepotastine ophthalmic solution in acute allergic conjunctivitis.

In May 2007 we announced results from the preliminary analysis of our U.S. Phase II/III clinical study of bepotastine for the treatment of allergic conjunctivitis. The study evaluated two concentrations of bepotastine, each dosed once daily and twice daily. The primary endpoints of the study were the assessment of efficacy for bepotastine in treating ocular itching and redness. The preliminary results of the study demonstrate both concentrations were highly statistically significant in the reduction of the first primary endpoint, ocular itching, when dosed twice a day, and in one concentration when dosed once a day. In addition, both concentrations and dosing regimens produced highly statistically significant differences in the rapidity of response and the improvement in total nasal symptoms vs. placebo. In the preliminary evaluation of the second primary endpoint, ocular redness, bepotastine showed a trend toward clinical significance, but did not achieve statistical significance. Several ocular allergy products have been approved by the FDA based on Phase III clinical data demonstrating the achievement of statistical significance and clinical success for one of the primary endpoints, ocular itching or redness.

We plan to complete the Phase II/III study analysis and then discuss the results with the Food and Drug Administration to determine the remaining clinical studies required to confirm ocular safety and efficacy for the submission of an NDA for bepotastine for the treatment of allergic conjunctivitis.

In the Phase II/III study, there were no serious adverse events reported in patients dosed with bepotastine. Importantly, there were no reports of incidences of burning or stinging with either concentration and no reports of increases in ocular adverse events compared with placebo.