R-Tech Ueno: Start of the Patient Enrollment of a Phase 3 Clinical Study of Unoprostone (Development Code UF-021) Ophthalmic Solution for the Treatment of Retinitis Pigmentosa

TOKYO -- (BUSINESS WIRE) -- R-Tech Ueno (JASDAQ:4573) is pleased to announce the start of the patient enrollment of a Phase 3 clinical study with Unoprostone^{(note 1)} (development code UF-021) ophthalmic solution that are being developed in our company for the treatment of retinitis pigmentosa^{(note 2)}.

The Phase 3 clinical study with UF-021 ophthalmic solution for treatment of retinitis pigmentosa (ClinicalTrials.gov Identifier:NCT01786395), for which an effective therapy has not been currently established, is a multicenter study using a placebo (without the active ingredient) as a control carried out based on Good Clinical Practice (GCP) in patients with visual field constriction and then deterioration of vision. This is a randomized double-masked controlled study for 52 weeks for efficacy, followed by the open trial study of UF-021 for a further 52 weeks for safety. The target sample size is 180 patients and the study is being carried out at 38 sites nationwide.

The president of R-Tech Ueno, an ophthalmologist, Yukihiko Mashima, MD, PhD commented as follows.
"I have seen many patients suffering from intractable diseases for many years as an ophthalmologist. Among these diseases, retinitis pigmentosa is a hereditary retinochoroidal disease, possibly resulting in progressive night blindness and visual field constriction as well as severe visual loss or blindness at the end stage of the disease. Although the disease is designated as an intractable disease by the national government, appropriate therapeutic drugs or therapeutic methods have not been established yet. Therefore, I longed to develop the first therapeutic drug for unmet medical needs, and I planned to develop a therapeutic drug for retinitis pigmentosa since immediately after participating in R-Tech Ueno (in April 2005).

A Phase 1 clinical study with Unoprostone ophthalmic solution was completed in 2008, and a Phase 2 clinical study was completed in February 2010. As a result, promising results were obtained leading to an increase in the number of the patients whose central retina sensitivity improved.
I am very glad that the first registration of the last stage, a Phase 3 clinical study, has been reached now. This study will be conducted with the strong support of many ophthalmologists, the patients and their family in addition to the governmental support of the Japan Science and Technology Agency (JST)^{(note 3)}. R-Tech Ueno will make best efforts to rapidly complete the registration and to deliver this new therapeutic drug to the many patients who have long awaited this treatment."

As a result of the above, there are no changes to the business forecasts throughout the year that were published on February 12, 2013.

(note 1) About Unoprostone
Prostones, a class of functional fatty acids which were first discovered in the 1980s by Dr. Ryuji Ueno, the founder of R-Tech Ueno, are compounds having effective localized physiological action as drugs, while being largely without the various systemic adverse reactions of prostaglandins themselves. Rescula^® Eye Drops 0.12% (generic name: unoprostone isopropyl), which obtained market approval in 1994 for treatment of glaucoma and ocular hypertension, was the world's first prostone drug. It opens ion channels (BK channel or Maxi-K channel) and not only lowers intraocular pressure, it is also reported to protect optic nerves (in vitro) and improve ocular blood flow in normal tension glaucoma. Since its release in 1994, it has been approved in 45 countries. In 2009 the concentration of preservative contained in Rescula^® Eye Drops 0.12% was reduced by a change in the formulation, and in 2010 storage at room temperature instead of in a cold place became possible. Rescula^® Eye Drops 0.12% is also marketed in South Korea and Taiwan.
We are also developing eye drops for retinitis pigmentosa with unoprostone as the main ingredient, and a phase 2 clinical trial indicated that the number of patients whose retina sensitivity in the central ocular fundus deteriorated was reduced (press releases of June 3 and July 15, 2010). The development of retinitis pigmentosa treatment by unoprostone in Japan was greatly honored to be adopted in the Adaptable and Seamless Technology Program through Target-Driven R&D (A-STEP) as "Full-scale R&D Stage - Practical Application Type (Contract Development)"by the Japan Science and Technology Agency (JST) (press release of February 1, 2013), and we are further increasing our efforts for early approval of this drug.
We licensed the overseas development and commercialization rights for unoprostone to Sucampo Pharmaceuticals, Inc. (Sucampo), for the United States and Canada in 2009, and then for the United States, Canada and the rest of the world excluding our own territories (Japan, South Korea, Taiwan and China) in 2011. While we retain the exclusive rights to manufacture and supply unoprostone products in our territory, we have an efficient partnership with Sucampo for overseas development of unoprostone. In the United States, unoprostone is designated by the FDA as an orphan drug for the treatment of retinitis pigmentosa, and we intend to make a new drug application to the FDA with unoprostone for retinitis pigmentosa in cooperation with Sucampo.

(note 2) About Retinitis Pigmentosa
Retinitis pigmentosa is a hereditary disease and its prevalence rate is said to be about 1 in 5000 people in the world and 1 in 4000 - 8000 people in Japan. When this number is applied to the population of Japan, 128 million people, the number of patients with retinitis pigmentosa can be estimated as 16,000 - 32,000 people, which makes this disease an orphan disease. On the other hand, when projecting the number of patients with retinitis pigmentosa in the world from the world population, 6.75 billion people (2008), it can be estimated as 1.35 million people. When retinitis pigmentosa progresses, patients suffer progressive night blindness, where it becomes difficult to see in dim light, or visual field constriction and then deterioration of vision. In the end stage, they may suffer from severe visual loss or even blindness. It is designated as an intractable disease and appropriate therapeutic drugs or therapeutic methods have not been established at the moment. According to the report by the "Research Study Group Regarding Retinochoroidal and Optic Atrophy", a specified disease treatment research program of the Ministry of Health, Labour and Welfare (MHLW) in 2005, retinitis pigmentosa is the 3^rd cause for impaired vision and especially in patients aged 60 or under it is the leading cause for impaired vision.

Accreditation of Retinitis Pigmentosa as a Specified Disease
Some diseases are very difficult to treat, they chronically develop, leave after-effects and make it extremely difficult or impossible for the patient to return to society, require a high medical cost, cause a heavy burden both domestically and mentally such as financial problems and nursing care and furthermore, as they are rare diseases they need to be studied on a nationwide scale. MHLW designates such diseases as intractable diseases. Currently, 130 diseases are designated as intractable diseases. Retinitis pigmentosa is a research target of the clinical research study area of the Research for Overcoming Intractable Diseases, MHLW. Disease number 33. Additionally, among the 130 intractable diseases, 56 are accredited as "specified diseases" and receive public fund assistance for medical expenses. Retinitis pigmentosa is one of the "specified diseases" and is covered by public fund assistance for medical expenses. Diseases subsidized for medical expenses of designated intractable diseases: disease number 37.
Reference: Japan Intractable Disease Information Center www.nanbyou.or.jp/sikkan/114_i.htm

(note 3) About the substantial support of the Japan Science and Technology Agency (JST)
The development of Unoprostone ophthalmic solution for patients with retinitis pigmentosa by R-Tech Ueno, Ltd. was adopted in the Adaptable and Seamless Technology Transfer Program through Target-Driven R&D (A-STEP) as a "Practical Application Type (Contract Development)" by the Japan Science and Technology Agency (JST) under the control of the Ministry of Education, Culture, Sports, Science and Technology (from the press release of February 1, 2013). A-STEP is a technology transfer program targeting the research and development (R&D) phase for practical applications based on research results generated from universities or official institutes. This program provides a participating institution with a total R&D funding of up to 2 billion yen for up to 7 years. If the development is successful, the participating institution repays the total amount of the provided funding by paying royalties based on product sales. If the development is not successful, the participating institution repays 10% of the provided funding.
Reference: Summary of A-STEP www.jst.go.jp/pr/info/info912/sankou1.html

・About R-Tech Ueno, Ltd.
R-Tech Ueno is a bio venture company established in September 1989 for the purpose of R&D and marketing of drugs. Under the leadership of the CEO, also a medical doctor, the company is developing new drugs on the theme "Physician-Oriented New Drug Innovation", targeting ophthalmologic and dermatologic diseases that previously had no effective therapeutic agent.
We aim at becoming a "global pharmaceutical company specializing in specific fields (ophthalmology and dermatology) and developing and selling pharmaceutical products through the eyes of doctors." We are promoting the development of new drugs for unmet medical needs for which the government provides recommendations and assistance, orphan drugs and the drugs in the field of anti-aging (lifestyle drugs).