Otsuka Pharmaceutical Co., Ltd.

May 9, 2013

Acucela and Otsuka Pharmaceutical Announce Phase IIa Clinical Results of Emixustat
Hydrochloride (ACU-4429) in Patients with Geographic Atrophy (GA) Associated with Dry
Age-related Macular Degeneration (AMD) at ARVO 2013 Annual Meeting

  • There are currently no medications approved to treat GA associated with dry AMD - a disease that could result in irreversible vision loss
  • The companies are co-developing emixustat hydrochloride, currently in phase IIb/III development, in North America

SEATTLE (May 8, 2013) and TOKYO (May 9, 2013) - Acucela Inc., a clinical-stage biotechnology company focused on developing therapies for sight-threatening diseases, and Otsuka Pharmaceutical Co., Ltd., (Otsuka) a Japan-based, "big venture" pharmaceutical company, today announced results from a recently completed phase IIa study of emixustat hydrochloride in patients with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD.) The results were presented by Pravin Dugel, MD, Managing Partner, Retinal Consultants of Arizona during a podium session at The Association for Research in Vision and Ophthalmology (ARVO) 2013 Annual Meeting.

Emixustat hydrochloride is under investigation to determine whether it slows the progression of GA in patients with GA associated with dry AMD. The oral availability of emixustat hydrochloride and its ability to specifically target the visual cycle represent a potential new therapeutic approach for the treatment of AMD. AMD is the most common cause of irreversible vision loss in the developed world, the overwhelming majority of which is associated with dry AMD. There are currently no medications approved to treat GA associated with dry AMD.

Phase IIa Study Design and Results

The purpose of the study was to assess the safety and tolerability of various emixustat hydrochloride doses in subjects with GA compared with placebo. In addition, the study included electroretinography tests (ERGs) to confirm the biological activity of emixustat hydrochloride in the retina. Seventy-two patients were randomly assigned to either emixustat hydrochloride (2, 5, 7 or 10 mg in the morning or 5 mg in the evening) or placebo, administered daily for up to 90 days. Adverse events and data on other safety parameters were collected. The clinical study results demonstrated safety and tolerability of the doses evaluated and confirmed the biological activity of orally administered emixustat hydrochloride. Emixustat hydrochloride is currently in a phase IIb/III clinical trial for the treatment of GA associated with dry AMD and was granted Fast Track status by the U.S. Food and Drug Administration in March 2010 for the treatment of GA associated with dry AMD.

Dr. Dugel stated, "This proof-of-concept study demonstrated a dose-dependent biologic effect and emixustat hydrochloride's ability to modulate the visual cycle, supporting further investigation into its potential to slow the growth of geographic atrophy lesions and potentially preserve sight."

Prior to this study, emixustat hydrochloride had been administered to a total of 125 healthy subjects. In 2012, Acucela announced interim phase IIa results evaluating emixustat hydrochloride in patients with GA associated with dry AMD. The three-month study presented at the ARVO meeting today was the first study in the target dry AMD patient population and provided support that further studies are warranted.

About Dry Age-related Macular Degeneration (AMD)

There are more than 10 million people in the US and more than 120 million people worldwide who have age-related macular degeneration (1). AMD is associated with irreversible vision loss, the overwhelming majority of which is due to the dry form of AMD, representing approximately 90% of all cases. Dry AMD occurs when the light-sensitive cells in the back of the eye slowly deteriorate, gradually blurring the central field of vision. As the disease advances, and when patients typically present with GA, the blurred vision slowly progresses to blindness in affected areas of the eye.

"Early detection and treatment are critical for treating AMD, which has the potential to rob patients of their sight--a devastating possibility for anyone," noted Dr. Dugel.

About the Acucela/Otsuka Pharmaceutical Emixustat Hydrochloride Agreement

Acucela and Otsuka Pharmaceutical entered into an agreement on September 4, 2008 to co-develop Acucela's emixustat hydrochloride in North America. In addition, Otsuka Pharmaceutical acquired the exclusive development and commercialization rights in Asia, the Pacific, the Middle East and North Africa while Acucela has retained all rights in Europe and other countries outside of Otsuka's exclusive territory.