1. No category

May 7, 2015
To whom it may concerned
R-Tech Ueno, Ltd.
(JASDAQ・Code4573)
Head Office: 1-1-7 Uchisaiwai-cho, Chiyoda-ku, Tokyo
Representative: Yukihiko Mashima,Representative Director & President
Contact: Koji Nakamura, Business Management Department
TEL: 03(3596) 8011
Termination of License Agreements for Unoprostone
R-Tech Ueno, Ltd. (RTU) today announced it has signed a termination agreement with Sucampo AG (SAG),
one of the subsidiaries of Sucampo Pharmaceuticals, Inc. (NASDAQ: SCMP) (Sucampo), which terminates,
effective May 6, 2015, all license agreements for unoprostone (Note 1).
(1) Background and Outlines
1) We entered into, on April 23th, 2009, Unoprostone NDA Transfer, Patent and Know-how Licensing, and
Data Sharing Agreement, as well as Exclusive Manufacturing and Supply Agreement, with Sucampo
Pharma Americas, Inc. (subsequently succeeded by SAG) for Unoprostone (Rescula®) eyedrop products
for Glaucoma and Ocular Hypertension indications for countries of the United States and Canada. (Refer to
our press release dated April 24th, 2009.)
2) We entered into, on March 22th, 2011, Exclusive License Agreement with Sucampo Manufacturing &
Research AG (subsequently succeeded by SAG) to develop, manufacture, and commercialize Unoprostone
in all countries excluding Japan, the People’s Republic of China, Taiwan, Republic of Korea and North
America (United States and Canada). (Refer to our press lease dated March 22th, 2011.)
3) Sucampo, as a result of changing their business strategies, made the decision (regarding which, refer to
Sucampo’s press release dated March 9th, 2015), and we agreed, to terminate the agreements. Upon
termination, all rights which had been granted to SAG in relation to Unoprostone reverted to, and certain
other associated assets owned by SAG were acquired by, RTU. We are expecting, under a new framework,
to maximize our operating revenue by pursuing development, manufacture and commercialization of
Unoprostone, including expanding indications.
(2) About the contracting party
SAG is one of the wholly-owned subsidiaries of Sucampo.
(3) Effect on our performance
Potential effects of this arrangement on our business performance are minimal. Nevertheless, we will
reflect such in the full-year earnings forecast for the fiscal year ending March 31, 2016.
The President of RTU, Yukihiko Mashima, MD, PhD, an ophthalmologist, made the following statements:
“Our marketing and development of Unoprostone has been limited to Japan, Korea, Taiwan and China, with
other countries around the globe being in the hands of SAG, as our licensee. As a result of the termination
of the agreements with SAG, RTU now solely owns and controls all associated rights on a global basis.
With the United States NDA for Rescula ophthalmic solution acquired from SAG, we will, in furtherance of
the achievements we have made to date in marketing and promotion in Japan, again take an aggressive
approach to overseas markets under our global strategies. We will restructure our development strategies
on a global basis in relation to the ophthalmic solution currently being developed by us in Japan for the
treatment of retinitis pigmentosa (Note 2), regarding which, please refer to our press release dated March 9th,
2015, taking advantage of the orphan drug designations in the United States and EU acquired from SAG.
Further, our acquisition from SAG of patents for the treatment of AMD (Note 3) will enable us to take the
initiative to develop, on a global basis, pharmaceutical products to treat geographic atrophy (failing vision)
(Note 4)
that develops after anti-VEGF (Note 5) treatment, regarding which please refer to our press release dated
April 7th, 2014. We now have a chance to develop in Japan new treatments for these two unmet medical
needs around the globe. Also included in the assets acquired from SAG are certain patents for the
treatment of asthenopia (Note 6). We will study development of new ophthalmic drugs for relief of stress.
Rescula® eye drops (0.12% Unoprostone), developed by Dr. Ryuji Ueno, MD, PhD, PhD who is a founder of
R-Tech Ueno, have been on the Japanese market for 20 years due to efficacy and safe issue. R-Tech Ueno regards
a characteristic of safe Unoprostone profile, and will challenge to expand indications of Unoprostone for unmet
medical needs with developing new formulations as a life-cycle management.”
(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. Unoprostone normalizes damaged cells or tissues through its BK
channel opening effect.
(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 including– Japan. When
this number is applied to the population of Japan, 126 million people, the number of patients with retinitis pigmentosa can be estimated as
30,000 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, 6.94 billion people (World Health Statistics 2013 published by WHO), it can be estimated
as 1.39 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 Chorioretinal and Optic Atrophy”, a specified disease treatment
research program of the Ministry of Health, Labour and Welfare (MHLW), retinitis pigmentosa is the 3rd 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 AMD
AMD is a disease that results in atrophy and macular degeneration with aging. In Japan, it is the fourth most common causative disease for
vision loss. AMD is also a major cause of adult anopsia and vision loss in the United States and several European countries. There are two
types of aged macular degeneration: exudative(wet) AMD and atrophic(dry) AMD. In wet AMD, neovascular vessels grow from the choroid
and appear under the retina, where blood and exudate from the neovascular blood vessels accumulate. The accumulation subsequently causes
elevation of the macular area and retinal detachment, resulting in vision loss. In dry AMD, geographic atrophy lesions that develop in the
macular area cause retinal atrophy that can result in vision loss. There are numerous patients in Europe and the United States who have dry
AMD without vascularization. AMD patients can take oral supplements; however, there is currently no drug that is effective for the disease.
Although dry AMD results in vision loss, it is rare for the patient to lose their eyesight. In contrast, there are treatments for wet AMD,
including photodynamic therapy (PDT) and medications with anti-VEGF. Without treatment, an AMD patient will experience severe vision
impairment or loss. At present, three types of anti-VEGF drugs have been approved.
The number of AMD patients is estimated to be 690,000 in Japan (Japan Intractable Diseases Information Center), 10,000,000 in the United
States, and 100,000,000 worldwide.
(Note 4) About geographic atrophy
Geographic atrophy lesions of the macular area (thinned-out retina)
Reference: quoted from the homepage of “Japan Intractable Diseases Information Center” (April 2015).
http://www.nanbyou.or.jp/entry/67
(Note 5) About VEGF (Vascular endothelial growth factor)
Vascular endothelial growth factor (VEGF) is a glycoprotein, which promotes the proliferation of vascular endothelial cells and angiogenesis.
When cells and tissues are exposed to hypoxic conditions, VEGF levels increase resulting in the formation of new blood vessels and an
increased supply of oxygen. Meanwhile, in diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and retinal vein
occlusion, hypoxia promotes VEGF production, leading to pathological vasculature formation also known as neovasculization.
Neovasculization leads to intraocular bleeding and retinal detachment, resulting in severe sight loss. Anti-VEGF agents as ranibizumab
(Lucentis®), aflibercept (Eylea®), and pagaptanib (Macgen®) are approved for ophthalmic disorders in Japan.
(Note 6) About asthenopia
Asthenopia is an ophthalmological condition of having fatigue, pain in or around the eyes, blurred vision, headache and nausea with the use of
the eyes, which is too severe not to be improved even after enough sleep. The number of patients has been increased due to the mobile devices
and computers. Though it does not lead to loss of eyesight, it has a major impact on the quality of life. This disease is known in connection
with stress and partially with eye adjustment dysfunction. Eye adjustment is a function to focus on a specific object. When this is damaged, the
eyes become not able to focus on, then, nonspecific symptoms such as fatigue, headache, stiff shoulders and nausea are induced.
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 to become 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 such as orphan drugs and the drugs in the field of anti-aging (lifestyle drugs).
R-Tech Ueno Forward-Looking Statement
The forward-looking statements contained in this press release are created based on the presumably valid data at the present moment, however,
the company does not provide any validation or guarantees on such statements. Please refer to such statements with awareness that actual
performance of the company may differ materially from those in such forward-looking statements. In addition, statement regarding industry,
etc. are also created based on various types of presumably reliable data, however, the company does not provide guarantee on accuracy or
completeness of such statement. The press release are provided based on the premise that the readers would refer to the contained information
in their own judgment and responsibility for any purpose, and the company shall not assume any kind of liabilities whatsoever.
About Sucampo Pharmaceuticals, Inc.
Sucampo Pharmaceuticals, Inc. is focused on the development and commercialization of medicines that meet major unmet medical needs of
patients worldwide. Sucampo has one marketed product – AMITIZA® – and a pipeline of drug candidates in clinical development. A global
company, Sucampo is headquartered in Bethesda, Maryland, and has operations in Japan, Switzerland and the United Kingdom. For more
information, please visit www.sucampo.com.
The Sucampo logo and the tagline, The Science of Innovation, are registered trademarks of Sucampo AG. AMITIZA® is a registered
trademark of Sucampo AG.
Sucampo Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These
statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially
from those set forth in the statements. The forward-looking statements may include statements regarding product development, product
potential, future financial and operating results, and other statements that are not historical facts. The following factors, among others, could
cause actual results to differ from those set forth in the forward-looking statements: the impact of pharmaceutical industry regulation and
health care legislation; the ability of Sucampo to develop and commercialize existing and pipeline products; Sucampo's ability to accurately
predict future market conditions; dependence on the effectiveness of Sucampo's patents and other protections for innovative products; the risk
of new and changing regulation and health policies in the U.S. and internationally; the effects of competitive products on Sucampo's products;
and the exposure to litigation and/or regulatory actions.
No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Sucampo undertakes no
obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
Forward-looking statements in this presentation should be evaluated together with the many uncertainties that affect Sucampo's business,
particularly those mentioned in the risk factors and cautionary statements in Sucampo's most recent Form 10-K as filed with the Securities and
Exchange Commission on March 9, 2015.
END