Announcement on Collaborative Development of Therapeutic Agent


Announcement on Collaborative Development of Therapeutic Agent
May18, 2015
To those concerned
R-Tech Ueno, Ltd.
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
Announcement on Collaborative Development of Therapeutic Agent for Diabetic
Retinopathy and Diabetic Macular Edema Utilizing VAP-1 Inhibitor (RTU-1096) with
Hokkaido University
R-Tech Ueno, Ltd. has announced plans to conduct collaborative research with a group led by Professor
Susumu Ishida and Associate Professor Kousuke Noda of the Department of Ophthalmology, Hokkaido
University Graduate School of Medicine. The research is in the application of a novel VAP-1 inhibitor (Note 1)
(Development Code: RTU-1096), which is under our development for treatment of diabetic retinopathy (DR)
(Note 2)
and diabetic macular edema (DME) (Note 3).
RTU-1096 is a VAP-1 inhibitor, having an anti-inflammatory and immunomodulatory effect that is currently
undergoing a Phase I clinical trial in Japan (Please refer to our press release dated October 20th, 2014). This
collaborative research is to conduct an examination at Hokkaido University to verify the therapeutic effect of
RTU-1096 on diabetes ophthalmic complications, such as DR and DME. This examination serves to explore
the possibility of the clinical application of the VAP-1 inhibitor for treating DR and DME, in preparation for
the POC (Proof of Concept) trials (Note 4) in the future, otherwise known as the Early Phase II clinical trials.
Going forward, we will further accelerate development of the VAP-1 inhibitor as an innovative treatment,
setting diabetic complications of DR and DME as the top priority target disease.
Yukihiko Mashima MD, an ophthalmologist and President of the company, has stated as follows:
"In recent years, the increase of health care costs associated with the growing number of diabetes patients has
become a global concern. In Japan, the population of diabetic patients is more than 20 million people,
including potential patients, and the patients with DR—one of the diabetic complications—which accounts for
at least 3 million people.
While the population of patients with proliferative DR causing sight loss has decreased, a specific DR that
causes edema in the macular region (central retina) resulting in deteriorating vision (DME) is becoming a
growing concern among the patients. The current treatment options for DME include photocoagulation, steroid
injections (intraocular injection, injection into the Tenon’s capsule), and vitrectomy. Recently, intraocular
injection of an anti-VEGF therapeutic agent (Note 5) has become a mainstream treatment. As recurrence of this
condition is persistent, the patients require a high frequency of anti-VEGF agent injections annually; however,
the drug price is extremely high, and that is one of the causes for increased health care costs. Given these
situations, many clinical researches among the physician are actively carried out regarding how to reduce the
frequency of anti-VEGF therapeutic agent injections by combining them with a photocoagulation and/or
steroid injection, while anti-VEGF agent injection is recognized as the preferred treatment. We are planning to
find a solution to this problem through this collaborative research. Considering the policy to extend a healthy
life, as conducted by Ministry of Health, Labour and Welfare, as well as the perspective of medical economy, it
is necessary to proceed with the strategy to suppress the increasing population of visually impaired patients
suffering from DR.
Diabetic patients have characteristically increased VAP-1 activity in their blood—considered one of the causes
of complications. The VAP-1 inhibitor RTU-1096 is an agent that is First in Class (Note 6) (First-in-Human use
(Note 7)
) and is expected to exert a therapeutic efficacy by inhibiting VAP-1 activity in the blood. Accordingly,
we believe it will be possible to use this inhibitor (oral medicine) in combination with an intraocular injection
of an anti-VEGF agent for treatment of DME. We intend to conduct collaborative research with the
Department of Ophthalmology, Hokkaido University Graduate School of Medicine, where basic research and
clinical research of DR and age-related macular degeneration are proactively conducted. We will further
develop the effective treatment utilizing this inhibitor, and aim to start POC trials (early Phase II clinical trials)
mainly at Hokkaido University Hospital."
The above venture will not contribute to any revisions to the earnings forecasts of the second cumulative
quarter and the full year previously announced on May 14, 2015.
(Note 1) VAP-1 Inhibitor
VAP-1 (vascular adhesion protein-1) is also known as semicarbazide sensitive amine oxidase (SSAO). There are two forms of this protein: one
exists in vascular endothelium as a membrane-binding molecule (VAP-1) and the other exists in serum as a free molecule (SSAO), sometimes
described as VAP-1/SSAO. The former has an adhesive function with leukocytes (granulocyte related to inflammation, lymphocytes and
monocytes related to inflammation and immunity) and mainly associated with inflammation. The latter detoxifies amines inside a living body by
amine oxidase activity. VAP-1/SSAO is a glycoprotein.. VAP-1/SSAO activity becomes increased in various tissues and in the serum of patients
with Diabetes, atopic dermatitis, obesity, arterial sclerosis, heart diseases, etc. Therefore, the inhibitor is expected to control such excess VAP1/SSAO and normalize its functions.
(Note 2) Diabetic retinopathy (DR)
DR is one of the three major complications of Diabetes. The prevalence of DR is as high as 80% in patients suffering Diabetes for 20 years or
longer. Currently, DR is the second leading cause of sight-related disabilities. There are two types of DR: proliferative DR leads to sight loss,
while non-proliferative DR may be improved by controlling blood glucose levels. The current treatment options for proliferative DR include
photocoagulation and vitrectomy. Global diabetes population is reported as 386.7 million people (in 2014), and the prevalence among 20-79
years-old adults is 8.3%, which means one in twelve adults is estimated to suffer from diabetic. Current adult diabetes population in Japan is 9.5
million people (such of pre-diabetic is 11 million people). Japan's diabetes population is 10th largest in the world.
(Note 3) Diabetes Macular Edema (DME)
For patients who developed DR, there is a possibility that edema occurs in the macula part in all stages. Macular edema deteriorates vision and
inevitably affects patients’ daily lives significantly. Establishing an appropriate treatment is an important challenge for ophthalmologists. Two
factors cause macular edema: systemic factors and local factors. The systemic factor relates strongly to lifestyle-related diseases, such as high
blood sugar, hypertension, hyperlipidemia, obesity, and renal disease. The local factor is capillary failure due to high blood sugar.
(Note 4) POC Trials
Proof of Concept (POC) in an innovative drug development that refers to a trial to examine a new drug candidate at the stage of research and
development, concerning whether the concept of such a drug development is correct. The trial verifies the drug’s efficacy and safety, and its result
serves to enhance development accuracy in the innovative drug development.
(Note 5) Anti-VEGF therapeutics agent
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. 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. And neovasculization leads to
intraocular bleeding and retinal detachment, resulting in severe sight loss. Currently approved anti-VEGF agents for ophthalmic disease
application (intraocular injection drugs) are ranibizumab (Lucentis®), Aflibercept (Eylea®), and Pegaptanib (Macugen®).
(Note 6) First in Class
First in Class refers to the first appearance of a pharmaceutical product on the market among the pharmaceutical products of relevant mechanism.
(Note 7) First-in-Human Use
First-in-Human use refers to a clinical trial to administer the test agent to a human body for the first time during the course of pharmaceutical
product developments.
・About Department of Ophthalmology, Graduate School of Medicine, Hokkaido University
Department of Ophthalmology of Graduate School of Medicine of Hokkaido University has long played a central role for the research and the
medical care in ophthalmology field since it was launched in Faculty of Medicine of Hokkaido Imperial University on May 15 1922 (Taisho 11th).
Professor Susumu Ishida took up the post as the 6th professor of the department in April 2009 and established 12 specific outpatient clinics. He
has continuously improved the organization of the department to enable to treat all eye diseases. In addition, the department involves a laboratory
of eye cell biology and visual sciences that consists of 5 research groups for retinal cell biology (vasculature), retinal cell biology (neuron), eye
immunology, eye neoplastic pathology, and corneal cell biology. They are performing basic researches that aim to reveal pathology of various eye
diseases and develop new therapeutic methods. The results have been presented in many good peer-reviewed journals and international
・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).