ASTELLASACCESS TO HEALTH INITIATIVES

2-5-1, Nihonbashi-Honcho, Chuo-Ku, Tokyo 103-8411, Japan

Tel. +81-3-3244-3000 (pilot number)

ASTELLAS’ RAISON D’ETRE ANDACCESS TO HEALTH INITIATIVES

Based on our stated business

philosophy, our unchanging identity

is to turn innovation into patient’s

value and to deliver this for patients

worldwide. Our business is creating

new medicines that will contribute

to better health for people around

the world which is highly connected

to social value. We also recognize

that, as a good corporate citizen,

we should actively engage in activi-

ties to benefit society to strengthen

the healthcare environment and

support the healthy lives of people

around the world.

There are two aspects to Corpo-

rate Social Responsibility (CSR) at

Astellas. The first is “value protec-

tion,” which contributes to the sus-

tainable growth of society and the

Company through measures such

as environmental activities and

rigorous compliance. The second

aspect is “value creation,” which is

to create stakeholder value by solv-

ing social issues and, at the same

time, create enterprise value by as-

similating such a process into our

business growth and future busi-

ness opportunities. At Astellas, we

pursue value creation in two ways:

through our core business, in which

we discover innovative new drugs

in therapeutic areas with high un-

met medical needs; and by imple-

menting a variety of activities that

aim to solve healthcare issues in re-

gions where access to healthcare,

including drug treatment, is inad-

equate. At Astellas, we recognize

these efforts as “Access to Health”

initiatives.

As an example of “Access to

Health” initiatives, combatting ne-

glected tropical diseases (NTDs) is

an issue addressed in global health,

where Astellas can leverage its

expertise and strengths. We have

established and joined collabora-

tive research and development pro-

grams for NTDs with various public-

private partners. At the same time,

we believe that these initiatives will

generate synergies with our busi-

ness activities from a long-term

perspective.

Contribute toward improving the health of people around the world

through the provision of innovative and reliable pharmaceutical products

Astellas Raison D’être

Since November 2010, Masafumi Nogimori, Representative Director and Chairman of our company, has served as Vice President of the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), whose membership includes R&D-driven pharmaceutical companies and pharmaceutical manu-facturers associations. Nogimori has repeatedly visited international organizations, the governments of each country, and related NGOs to exchange opinions on problems, such as global health, where the pharmaceuti-cal industry can contribute to finding solutions. Astellas is making most of these activities in its implementa-tion of Access to Health initiatives.

Astellas Representative Director and Chairman Nogimori actively engages in dialog on global health issues

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Overall image of the Consortium

Astellas is exploring effective treat-ments for diseases caused by parasitic protozoa and dengue fever, which are endemic to the tropical regions of Af-rica, Central and South America, and South Asia. To tackle this challenge, we are leveraging cutting-edge tech-

nology and knowledge, and working closely with the University of Tokyo, To-kyo Institute of Technology, Nagasaki University, High Energy Accelerator Research Organization, National In-stitute of Advanced Industrial Science and Technology (AIST), and the non-

profit organization Drugs for Neglected Diseases initiative (DNDi).

Schistosomiasis is the third most prevalent tropical disease in Africa af-ter malaria soil-transmitted helminth infections. Left untreated, the disease (also known as bilharzia) can lead to anemia, stunted growth and impaired learning ability, and is fatal in the most serious cases.

The existing ‘gold standard’ treat-ment is praziquantel, which is safe and effective, and a tablet formulation is available for adults and school-age children but not for those below 6 years old.

For young children (< 6 years) treat-ment with the current praziquantel tablet is not appropriate:

• Insufficient clinical data in very young children

• Bitter taste leads to gagging or vomiting• The size of the current tablet is sig-

nificant

To address the above described gap, Astellas joined other international partners to develop and register a new pediatric formulation of praziquantel for the treatment of schistosomiasis in preschool-age children.

Drug-discovery Research Consortium to Combat Neglected Tropical Diseases (NTDs)

Examples of Access to Health Initiatives

Development of Pediatric Formulation for Schistosomiasis Treatment

Source: Prof. J. Russell Stothard, Liverpool School of Tropical Medicine

For more information on this international non-profit partner-ship, please see page 19-21.

For more information on this consortium, please see page 4-18.

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“Neglected tropical diseases” that have not been adequately addressed thus far

Infectious diseases caused by parasites, bacteria, and viruses run rampant in developing countries, mainly in remote parts and among the poor. They threaten health and cause poverty to spread and become entrenched, sometimes affect-

ing entire local communities. The world has not shown much concern for many of these infectious diseases, and since adequate measures have not been taken against them, they are referred to as “ne-glected tropical diseases (NTDs)”. The 17 NTDs that have been particularly targeted by the World Health Organization (WHO) are currently endemic in 149 countries or regions throughout the world. Although the spread of affected regions has at-

tracted attention in recent years with the globalization of social and economic activities, many patients with NTDs can-not obtain needed care or treatment medicines because of poverty and poor medical systems. At the same time, there is the issue that NTDs include some dis-eases for which safe and effective treat-ment medicines simply do not exist.

Today, when social and economic activity unfolds on a global scale, Japan is also proactively promoting efforts to solve the problems that confront

global health. The NTDs Drug-discovery Research Consortium, inaugurated in 2012 as a partnership of 5 Japanese research institutes, an interna-

tional NPO, and Astellas is one such effort.

Starting with this issue and extending for 6 installments, this series will introduce the activities of this consortium to grapple ambitiously with

the challenges of drug-discovery for NTDs as diseases for which safe and effective treatment drugs do not currently exist. In the first installment in

this issue, we asked members of the Astellas to comment on the purpose and significance of this consortium. We also spoke to Prof. Kiyoshi Kita

of the Department of Biomedical Chemistry, School of International Health, Graduate School of Medicine, The University of Tokyo, Japan’s leading

researcher on parasitic infectious diseases, who has been appointed to summarize the research of this consortium as a whole.

AN ALL-JAPAN EFFORT TO DISCOVER TREATMENT MEDICINES FOR NTDS

Global cooperation among industry, universities, governments, and NPOs to combat NTDs (Neglected Tropical Diseases)

Introducing an excerpt from the content on drug-discovery research on NTDs, published in Astellas Square

The watchword is “Open Innovation”

The parasite that causes this disease is a pro-tozoan of the Trypanosomatidae family, and the disease vector is the sand fly, Phlebotomus papatasi (photo). The disease takes 3 different forms – cutaneous, visceral, and mucocuta-neous leishmaniasis – depending on the type of protozoan infecting the patient. Outbreaks have been reported in 98 countries, chiefly in Asia, Africa, and South and Central America. Present treatment methods are fraught by dif-ficulties with dosing as well as the toxicity and cost of the medicines, and drug resistance is becoming a serious problem.

Leishmaniasis

©Prof. Frank Hadley Collins, Dir., Cntr. for Global Health and Infec-tious Diseases, Univ. of Notre Dame

The parasite that causes this disease is also a protozoan of the Trypanosoma-tidae family. Infection is spread through the feces of insects belonging to the Reduviidae family (photo). Chagas disease is mainly endemic to Latin America, but it is spread by blood transfusions, etc., and patients have recently been reported in North America, Europe, and the Western Pacific. The parasite ini-tially inhabits the bloodstream, causing fever and swollen lymph nodes. In the chronic phase, it causes damage to heart and digestive muscle, leading to the progression of heart diseases and in some cases, sudden death. There are safety and efficacy problems with the existing treatment methods.

Chagas disease

©CDC

Four diseases targeted by the NTDs Drug-discovery Research Consortium

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4

In order to respond to unmet medical needs

Amidst this situation, the NTDs Drug-discovery Research Consortium was created to grapple proactively with un-met medical needs, so as contribute to the improvement of global health by providing patients worldwide with new medicines. This consortium is comprised by the University of Tokyo, Tokyo Institute of Technology, Nagasaki University, High Energy Accelerator Research Organiza-tion (KEK), National Institute of Advanced Industrial Science and Technology (AIST), NPO DNDi, headquartered in Switzerland, and Astellas and it promotes collabora-tive research with the aim of discovering new treatment medicines for NTDs.

The 2 key characteristics of this collab-orative research consortium are its focus on the 4 NTDs of leishmaniasis, Chagas disease, African trypanosomiasis, and dengue fever/dengue hemorrhagic fever

and its “Open Innovation” approach to collaborative drug-discovery.

Four diseases with a high degree of need for new medicines are the drug-discovery targets

The major deciding factors in the selec-tion of the 4 diseases targeted for collab-orative research on drug-discovery were the extent of the unmet medical needs and the availability of experts with whom we could partner.

Dr. Hiroshi Suzuki, leader of the As-tellas Pharma Drug-discovery Research Department’s Tropical Disease Research Team (hereinafter referred to as the TDR team), described the background for the selection of the target diseases as follows: “We in Astellas Pharma’s Drug-discovery Research Department regarded our mission as finding ‘drug seeds’ – compounds that had the po-tential to grow into pharmaceuticals. We then proceeded to investigate from the

standpoint of the diseases for which new medicines were sought. Specifically, this came down to the points many patients were suffering from the disease and whether or not treatment medicines with an assurance of efficacy and safety were already in existence. Another important criterion was whether or not there were any experts that could partner with us in collaborative research on drug-discovery for NTDs that could lead to clinical devel-opment of ‘drug seeds’ as we work to-ward the final goal of delivering treatment medicines to the patients.”Through this selection process, the tar-gets for collaborative research on drug-discovery were ultimately narrowed down to 4 diseases for which there are no existing effective treatment medi-cines: leishmaniasis, Chagas disease, African trypanosomiasis, and dengue fever/dengue hemorrhagic fever, the last of which is the sole NTD for which the patient count continues to rise, with no treatment medicines available.

The parasite that causes this disease is a protozoan of the Trypanosoma-tidae family (photo), and the disease vector is the tsetse fly. During the in-cipient phase, the protozoan proliferates in the subcutaneous tissue, blood, and lymph, and systemic symptoms are manifested. It then infiltrates the central nervous systems, causing neurological disorders and sleep disor-ders that frequently lead to death. This disease is found only in 36 sub-Saharan countries inhabited by the tsetse fly. Existing treatment methods present problems from the standpoint of toxicity, the difficulty of administra-tion, and the safety and efficacy of the medicines.

African trypanosomiasis

©CDC/ Dr. Mae Melvin

This infectious disease is caused by the dengue virus, and the main disease

vector is Aedes aegypti (photo). There are 2 types: dengue fever, a non-

fatal febrile illness, and dengue hemorrhagic fever, which is more severe.

This disease is found in tropical and

subtropical regions inhabited by the

fly that is the vector, particularly in

Southeast Asia, South Asia, South and

Central America, and the countries of

the Caribbean, but also in Africa, Aus-

tralia, China, and Taiwan. No effective

treatment medicines are currently

available.

Dengue fever/dengue hemorrhagic fever

©Prof. Frank Hadley Collins, Dir., Cntr. for Global Health and Infectious Diseases, Univ. of Notre Dame

Source: Astellas Square No.52（2013 Vol.9 No.5）5

“Open Innovation” fanned research-ers’ will to succeed and deepened their passion for the project

Each of the research institutes partici-pating in this consortium plays its own specialized role while sharing information with the others. These roles include de-signing, developing, and operating NTDs drug-discovery databases incorporat-ing IT technology, evaluating molecules targeted in drug-discovery, drug design utilizing three-dimensional structure and low-molecular fragments, efficacy evalu-ation, and verifying the effects of medi-cines on pathogens.

“Ordinarily when we work on drug-discovery research at a pharmaceutical company, the name of the target disease

may not occasionally be open. Howev-er, in this consortium, not only was the target disease open knowledge but we were also able to share and discuss all of the information obtained in the course of the collaborative research. We were able to feel the merits of making information open, because it promoted smoother collaboration and helped take the re-search to the next level” (Suzuki).

Dr. Masaya Orita, who is in charge of the areas of information science and anal-ysis of three-dimensional structure in TDR team, describes his experience as fol-lows: “Nowadays, drug-discovery has be-come a ‘battle with information.’ For this reason, IT is essential to drug-discovery. Although exchange with experts in fields that differ greatly from medical and phar-maceutical science can be the source of some confusion, this is far outweighed by

the joy of learning something new.”As these comments show, the words

of each member of TDR team commu-nicate a pattern of collaboration in which efforts that transcend organizational frameworks serve as a good stimulus to researchers as they approach each day’s work with hopes and dreams.

Meeting the challenges of global health from a long-term perspective

This consortium is positioned as a new first step toward contributing to global health on the part of Osamu Chihara, CSR Group Leader in the Astellas Cor-porate Planning Department, has great expectations for it: “The development of treatment medicines for NTDs will lead

Members from the Graduate School of Medicine The University of Tokyo, (Prof. Kiyoshi Kita; Associate Prof. Daniel Ken Inaoka), Tokyo Institute of Technology (Prof. Yutaka Akiyama, Associate Prof. Masakazu Sekijima, Associate Prof.Takashi Ishida), and the Astellas Pharma Drug-discovery Research Department’s TDR team gathered together at the regular sectional meeting of the consortium, held every month.

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to the resolution of major health care problems that the world is now burdened with. Moreover, even in the sense of ful-filling our corporate social responsibility (CSR) as a pharmaceutical company, I would like to see us engaging in this con-sortium with a long-term perspective.”

Individual research institutes provide specialized technologies as all work as one toward the common goal of drug-discovery

Prof. Kiyoshi Kita of the Graduate School of Medicine, The University of Tokyo, has been assigned the role of summarizing all of the research conducted by this con-sortium.

Prof. Kita ascribes a high degree of significance to the framework that makes it possible for individual research insti-tutes to provide their own specialized technologies as all work together toward the common goal of drug-discovery: “I am extremely happy to see a pharma-ceutical company with a proven track record in drug-discovery turn its gaze toward global health and take the stance of working together with state-of-the-art technologies in completely different fields in an effort to develop treatment medi-cines for diseases that are not prevalent in Japan. I have very great expectations for this.” Prof. Kita also pointed out that the concept of this initiative in itself rep-resents an extremely ambitious experi-ment as a new model for drug-discovery, and suggested that it has the potential to go beyond treatment medicines for the 4 NTDs selected as targets of drug-discov-

ery this time and extend to drug-discov-ery in various other fields, beginning with treatment medicines for cancer.

The importance of creating a system to bridge the gap from academic to practical/clinical

Prof. Kita emphasized that this initiative will provide a great deal of momentum to move drug-discovery forward toward practical application. “However good the ‘seeds’ may be, they will never be of real use to the world unless you create paths by which they can find practical applica-tions. In other words, it is important to have a system that channels academic drug-discovery into clinical applications. This consortium brings together the

members who can play precisely that role in the project.”

The path to practical applications for the seeds generated by this consortium has been made surer and more realistic by having work proceed in collaboration with Astellas, a company with a wealth of experience in drug development and a global range of activity.

Prof. Kita concluded his remarks by speaking of his aspirations for the future: “I would like to raise this consortium’s initiatives to the level where they merit international attention, in the hope that we can create a world where every child born on this Earth will be able to live out his or her natural lifespan.”

Prof. Kiyoshi Kita of the Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo

Source: Astellas Square No.52（2013 Vol.9 No.5）7

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“Working in the background” to support the series of processes involved in drug-discovery with exceptional technology and a wealth of experience

Aiming to discover new medicines as early as possible, the NTDs Drug-discovery Re-search consortium takes the 2-pillared ap-proach of “searching for target candidates” and “searching for compounds” (Fig. 1).

In the “search for target candidates,” the search for molecules that are candidates for drug targets is performed on the basis of bioinformatics, which uses the techniques of information science to analyze biological data and findings, and a number of proteins are selected as targets of drug-discovery.

The “search for compounds” proceeds by 3 cutting-edge approaches: (1) IT Drug-discovery, (2) FE Drug-discovery, and (3) the Astellas compound library. In IT Drug-discovery, the 3-dimensional structure of the proteins that are the targets of drug-discovery are analyzed by supercomputer. The active compounds are then selected out, and a high-throughput assay employ-ing in silico screening and a robot is used to automatically evaluate the compounds at high speed. “In silico” is a term that means “within a computer (silicon chip)” by contrast with in vivo (in a living body) or in vitro (in a test tube). FE drug-discovery is a unique drug design method devel-oped by Astellas and the “FE” stands for Fragment Evolution. This method utilizes the Astellas compound library to search among low-molecular compounds known as “fragments” for fragment hits that could

bind with the proteins that are the targets of drug-discovery.

The process then moves on to elucidat-ing the binding mode for the fragment hit and drug target protein by X-ray crystal-lography, selecting out a number of lead compounds as new drug candidates, and proceeding to develop new treatment med-icines.

Drug-discovery research following this series of steps will be conducted on treat-ment medicines for dengue fever/dengue hemorrhagic fever by Nagasaki University, Tokyo Institute of Technology, and Astellas and on treatment medicines for the infec-tions caused by Trypanosoma protozoa (leishmaniasis, Chagas disease, and Afri-can trypanosomiasis) by Tokyo University, Tokyo Institute of Technology, High Energy Accelerator Research Organization, Na-

tional Institute of Advanced Industrial Sci-ence and Technology, and Astellas.

A concept of approaching problems from a higher level of specialization at the same time as a broader perspective

In this consortium, the University of Tokyo, with its abundant knowledge and experi-ence with anti-protozoan medicines, will support the research project as a whole, acting as the proverbial “strong man sup-porting the floor from below.” This work behind the scenes will consist of the search for, verification, and evaluation of target candidates and compounds for use in re-search on the development of treatment medicines for infections caused by Try-

The neglected tropical diseases (NTDs) Drug-discovery Research Consortium that has focused on 4 of these NTDs (leishmaniasis, Chagas disease,

African trypanosomiasis, and dengue fever/dengue hemorrhagic fever) and is working to develop treatment medicines is conducting joint research

along the Open Innovation model. In August of 2013, news media reported that blood donated by a person infected with Chagas disease had been

used in blood products in Japan. As socio-economic activity expands globally, this case brought home to us the realization that NTDs know no

national borders. In this issue we discuss the role of the University of Tokyo and the ultimate goals of this joint research with Prof. Kiyoshi Kita of the

Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, who is responsible for summarizing the entirety of the

consortium’s research, mainly concerning the evaluation and verification of the targets of drug-discovery.

FROM JAPAN TO THE WORLD:PHARMACEUTICALS TO TREAT INFECTIOUS DISEASES AT THE GLOBAL LEVEL

Prof. Kiyoshi Kita Ph.D. of the Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo

Fig. 1. Two approaches to drug-discovery research in the NTDs Drug-discovery Research Consortium

(Source materials provided by Prof. Kiyoshi Kita)

Global cooperation among industry, universities, governments, and NPOs to combat NTDs (Neglected Tropical Diseases)

The watchword is “Open Innovation”

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panosoma protozoa. If we take African trypanosomiasis as an

example of these infections and look at the life cycle of a protozoan of the Trypanoso-matidae family, we can get a solid sense of just how difficult it is to develop preven-tive vaccines and treatment medicines for these protozoal infections.

The life cycle of Trypanosoma brucei gambiense, the parasite that causes Af-rican trypanosomiasis, is complex. It re-peatedly metamorphoses within the host (tsetse flies and mammals such as humans (Fig. 2)), and each time, the structure and functions of its mitochondria undergo great changes. Moreover, the composition of the glycoproteins that cover the surface of the protozoan body changes little by little, making it possible for the parasite to craftily evade attack by the immune system of the host. This is also one of the reasons why no effective vaccines against these various diseases have yet been developed. The Trypanosoma protozoa that cause leish-maniasis and Chagas disease also have a similar life cycle.

The research conducted by Prof. Kita and his colleagues clearly showed that the mitochondrial respiratory chain of parasitic protozoa (the system by which a series of enzymes related to cell respiration trans-port electrons sequentially) has properties that differ from those of the mitochondria of the host mammals and can therefore serve as an important target for drug-discovery because it is at the same time essential to the proliferation of parasitic protozoa. In order to realize the goal of developing medicines with few side effects, it will be important to search for specific targets on the parasites.

Prof. Kita elaborates: “This consortium has made it possible to concentrate a higher degree of expertise on the task of narrowing down the range of drug target

proteins, and I have great hopes that it will promote the selection of lead compounds and accelerate the movement toward prac-tical application of the findings.”

A logical approach to Drug-discovery that makes abundant use of high-level technology and knowledge

The selection of lead compounds is like a journey that we traverse step by step. First, the efficacy of the compounds dis-covered through in silico screening must be confirmed in an enzyme system. Next, the growth-inhibiting activity of the compound against living parasites must be confirmed in an in vitro culture system. According to Prof. Kita, this gap between in silico and in vitro is extremely great, and even if an effect is observed in an enzyme system, it is com-mon for the compound to fail to show any effect in the culture system.

“In order to bridge the in silico – in vitro gap, it is necessary to clarify the causes for the lack of success in vitro and then take appropriate steps to overcome them” (Prof. Kita).

However, clearing that step from in silico to in vitro not only requires an extremely high level of specialized knowledge but also involves vast amounts of time and high costs. For this reason, a trend toward returning from in silico molecular design to random screening has even been observed in recent years in the United States and Europe.

“Japan is rich in outstanding sources of science and technology, beginning with large-scale synchrotron radiation beam lines for X-ray crystal structure analysis. In the spirit of ‘never give up,’ I would like to make full use of this high-level technology and knowledge to work toward bridging the

gap to drug-discovery through processes that unfold in a logical manner and are at the same time highly efficient.

This is the kind of thing that can only be achieved in a consortium of this type, which pursues drug-discovery research on the basis of a concept of open innovation” (Prof. Kita).

The desirable system for delivering medicines to patients needing treatment

When we consider that NTDs are diseases that are epidemic in the tropical regions of emerging nations separated from the in-dustrially advanced nations by a large eco-nomic gap, it becomes clear that not only must treatment medicines for NTDs be safe and effective, they must also be inexpen-sive, easy to take, and stable even in the hot environment of the tropics.

“There is great significance to the point that this consortium has powerful regional networks as well as the support of an in-ternational NPO, which provides it with a system for directly returning the fruits of the research to the patients.

In order to ensure that the medicines we develop get into the hands of patients requiring treatment in the regions where NTDs are epidemic, it will be to construct a project for that purpose, bringing onboard not only the researchers involved in drug-discovery but also cultural anthropologists, historians, econometricians, and policy makers, and then proceed to address the needs” Prof. Kita noted.

From scientifically advanced Japan, a wish to send out medicines that are useful at the global level

Prof. Kita concludes: “Japan’s high level of technological strength is held in high regard by other countries, that is true. The spirit that infuses these drug-discovery initiatives is the wish to see scientifically advanced Japan foster cooperation with researchers in various fields to bring about a fusion of cutting-edge science and technology that will lead to the development of medicines that can be used at the global level. Ulti-mately we want to see Japan send the fruits of this work out into the world. We would also like to pour our energies into training young researchers so that efforts to discover new medicines will continue on a global scale.”

Prof. Kiyoshi KitaCompleted first half of doctoral program in pharmaceutical

sciences at the University of Tokyo in 1974 and became an

assistant in the Department of Science. Became an assistant

at Juntendo University School of Medicine in 1983 and a lec-

turer in 1987. Became an associate professor at The Institute

of Medical Science, The University of Tokyo in 1991. Assumed

his present position in 1998.

Fig. 2. Life cycle of African trypanosome, the parasite that causes African trypanosomiasis

(Source materials provided by Prof. Kiyoshi Kita)

Source: Astellas Square No.53（2013 Vol.9 No.6）9

Many of the viral, bacterial, and parasitic in-fectious diseases that are epidemic among the tropical regions and poorest classes of developing countries have yet to be met with effective measures to combat disease. These diseases are referred to as NTDs in the sense that the world has not turned sufficient attention to them. Even if we limit the discussion to the 17 NTDs identified by the World Health Organization (WHO), the number of infected patients exceeds 1 billion worldwide. NTDs fetter economic activity in the regions where they are epi-demic, and they are one of the most impor-tant global health issues today.

Chagas diseases, which is epidemic in South and Central America, is spreading in the United States, Canada, and Europe, reflecting the increase in immigrants from affected areas. In August of 2013, the first confirmed case of someone receiving blood donated by a person infected with Chagas disease was reported in Japan. This news reawakened us to the fact that the prob-lems confronting global health are by no means limited to other countries.

One of the major characteristics of the NTDs Drug-discovery Research Consortium is the Open Innovation style of joint research. Each of the research institutes plays the re-spective role that best befits it given its high level of specialized knowledge, and the in-formation obtained through the process of joint research is made open and shared by all members to lead the project through to the final goal of drug-discovery.

Dr. Yutaka Akiyama, a professor in the Graduate School of Information Science and Engineering, Tokyo Institute of Tech-nology, described his motivation for partici-pating in the consortium as follows: “Often in conventional joint research, I had the feeling that my participation inevitably end-ed at some intermediate stage because of the constraints imposed by confidentiality. In this consortium, with its Open Innovation research system, I have found that the abil-ity to see the project through to the goal together with all of my fellow researchers is one of the most attractive features.”

Dr. Masakazu Sekijima and Dr. Takashi Ishida, also from Tokyo Institute of Technol-ogy, also find Open Innovation joint research very attractive and have great expectations of it. Dr. Ishida explained: “Because the need for our technology was clearly dem-onstrated in a true sense, we can provide the technology necessary to achieve the

goal. We derive a great sense of satisfac-tion when the technology we propose is being utilized effectively, creating a path leading toward the goal.” Dr. Sekijima, who has had opportunities to engage in joint re-search with Astellas for some time, believes that the fact that a mutual relationship of trust has been cultivated has led to smooth communication within the consortium.

The drug-discovery joint research is be-ing promoted in 2 main stages. At the first stage, data mining is performed on public information from published literature, etc. to extract information that is useful in search-ing for target molecules for anti-protozoan medicines and anti-dengue virus medi-cines. At the second stage, in silico screen-ing based on computer analysis is used to search for active compounds.

With the dual role of reducing/analyzing data at each stage of research and then performing physicochemical molecular simulations, the members of the Tokyo In-stitute of Technology Team draw upon the computational strengths afforded in large-scale calculations by “TSUBAME,” one of Japan’s top-level supercomputers.

The NTDs Drug-discovery Research Consortium was founded as one part of the solution to the problems confronting global health

Open Innovation joint research attractive because all can see the end goal together

Using Japan’s top-level computational science and technology to discover useful information from a vast amount of data

The NTDs Drug-discovery Research Consortium was created in 2012 to develop medicines for neglected tropical diseases (NTDs). In this issue, we speak with Professor Yutaka Akiyama, Dr. Masakazu Sekijima, and Dr. Takashi Ishida of Tokyo Institute of Technology, all of whom have contributed greatly to accelerating the pace of drug-discovery research through cutting-edge IT technology.

AIMING TO REALIZE SUPERCOMPUTER DRUG-DISCOVERY MAKING FULL USE OF CUTTING-EDGE IT TECHNOLOGY

Yutaka Akiyama, Ph.D. Professor, Graduate School of Information Science and Engineering, Tokyo Institute of Technology

Masakazu Sekijima, Ph.D. Associate Professor, Global Scientific Information and Computing Center, Tokyo Institute of Technology

Takashi Ishida, Ph.D.Associate Professor, Graduate School of Information Science and Engineering, Tokyo Institute of Technology

3Global cooperation among industry, universities, governments, and NPOs to combat NTDs (Neglected Tropical Diseases)

The watchword is “Open Innovation”

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TSUBAME is the supercomputer system operated by Tokyo Institute of Technology’s Global Scientific Information and Comput-ing Center (Fig. 1). It is an extremely high performing system for the graph manipu-lation that forms the basis of data mining, as well as the molecular dy-namics simulation that underlies in silico screening, and its comput-ing power is top class – not only within Japan but on the global level.

“TSUBAME is a supercomputer that combines the arithmetic unit’s computa-tional processors with graphics in an ideal form. The TSUBAME 2.5 that is presently being operated is capable of perform-ing 5.7 quadrillion operations per second, which represents an approximately 2.4-fold increase over the previous generation, TSUBAME 2.0” Dr. Sekijima explained.

The physicochemical molecular simulation that is the second role played by Tokyo In-stitute of Technology in this joint research, consists of using computers to search for compounds that firmly bind to the target protein. In other words, the objective is to find compounds that exert a therapeutic effect upon diseases by binding to the pro-teins that cause them.

The relationship between these proteins and compounds can be likened to a “key and keyhole” (Fig. 2), and researchers search for compounds that are a perfect fit from the standpoint of physicochemical interactions, such as 3-dimensional structure and energy at the time of binding. While it of course de-pends on the type of protein, Dr. Sekijima states that fewer than 1000 out of approxi-mately 100,000 compounds will satisfy the “key and keyhole” relationship to a certain level. Moreover, only about one-tenth or

one-hundredth of those will later be shown to possess actual activity in the assay.

“In order to make drug-discovery a reality, you need to increase the accuracy of calcu-lation while at the same time making a vast number of compounds the object of those calculations. It is no exaggeration to say that this is a feat that can only be accom-plished by a supercomputer” (Dr. Sekijima).

In this consortium, “iNTRODB,” the world’s first integrated data base for NTDs Drug-discovery research, is also contributing to the acceleration of research activity (Fig. 3). iNTRODB is a “2nd-generation” data base for the purpose of searching for in-formation that is useful in drug-discovery, and at present it has integrated all genetic information on the Trypanosoma protozoa (approx. 27,000 cases) with information on protein structure (approx. 7000 cases) and information on related compounds (approx. 1 million cases). Dr. Ishida explains: “One major point is that adding a variety of infor-mation on genes, proteins, and compounds has made it easier to obtain the information necessary to judge whether a drug target candidate is a good one or not.” In that it was designed from the standpoint of drug-discovery, this is a significant data base with high value added.

iNTRODB is highly regarded as an exam-ple of how close cooperation among Japa-nese research institutes and international NPOs can contribute to solving problems on a global scale, and it received the Minis-ter of Health, Labour and Welfare Award of the 11th annual Merit Awards for Industry-Academia-Government Collaboration in Au-gust 2013.

Even now, the data base is continu-ing to be improved under the advice and

guidance of Astellas and Dr. Kiyoshi Kita, a professor in the Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, who possesses a wealth of knowledge about anti-protozoan medicines.

Dr. Ishida describes his future aspirations for the project as follows: “Bioinformatics technology and computational science are powerful forces to make the process more efficient and faster while reducing costs. I would like to utilize these to contribute to the realization of drug-discovery at a lower cost.” Dr. Sekijima adds: “I would like to use supercomputers to get medicines into the hands of patients as soon as possible. I would then like to verify the contributions of supercomputer drug-discovery.”

Dr. Akiyama concludes: “Clearly there are opportunities for computational science to make contributions to the drug-discovery process. I would be happy to see a new era in which new talents and technologies can contribute to drug-discovery.”

With ultra-high-speed operational performance, “TSU-BAME” plays the leading role in supercomputer drug-discovery

Supercomputers are indispensable when it comes to finding the “key and keyhole relationship” from amongst a vast array of compounds

The “iNTRODB” integrated data base for NTDs Drug-discovery research, designed from the standpoint of drug-discovery

Great expectations for the contribu-tion of computational science in the drug-discovery process

Dr. Yutaka AkiyamaCompleted the doctoral course in Electrical Engineering at the Graduate School of Science and Technology, Keio University, in 1990. Worked for Electrotechnical Laboratory, Institute for Chemical Research, Kyoto University, and National Institute of Advanced Industrial Science and Technology before assuming present position in 2007.

Dr. Masakazu SekijimaCompleted doctoral course in Graduate School of Agriculture and Life Sciences, The University of Tokyo, in 2002. Worked for National Institute of Advanced Industrial Science and Technol-ogy before assuming present position in 2009.

Dr. Takashi IshidaCompleted doctoral course in Graduate School of Agriculture and Life Sciences, The University of Tokyo, in 2006. Worked for the Institute of Medical Science, The University of Tokyo before assuming present position in 2012.

Fig. 1. External appearance of TSUBAME 2.5 (Source: Tokyo Institute of Technology)

Fig. 2. Complex of protein and compound: A key and keyhole relationship (Source: Dr. Masakazu Sekijima)

Source: Astellas Square No.54（2014 Vol.10 No.1）

(Source: Dr. Takashi Ishida)

Fig. 3. Discovery of NTDs treatment medicines through the use of iNTRODB

11

The special characteristic of the NTDs Drug-discovery Research Consortium is that it conducts joint research using an Open Innovation model. All of the various participating institutes share information while fulfilling their roles as they work to-ward the common goal of early discovery of treatment medicines for NTDs.

In the 2nd and 3rd installments of this series, we introduced the process whereby researchers combine biological findings on the parasites and viruses that cause NTDs with the techniques of infor-mation science to search for proteins to target in drug-discovery.

This time, we introduce the research conducted at National Institute of Ad-vanced Industrial Science and Technol-ogy (AIST) and High Energy Accelerator Research Organization (KEK), which are proceeding to create a base for drug-discovery research through the use of advanced technologies in the engineering field to search for, evaluate, and structur-ally analyze target proteins and fragment hits that are active against them.

Structure-based drug design (SBDD) is a technique of drug-discovery that has de-veloped remarkably in recent years. Tradi-tionally, the search for fragment hits with

pharmacological activity against target proteins has literally been performed “by hand,” but SBDD has made it possible to analyze and compare the three-dimen-sional structure of complexes of target proteins and low-molecular compounds, which has facilitated drug design by giv-ing researchers a comprehensive under-standing of the mechanisms that block (or promote) the physiological activity of

From the standpoint of both treatment and prevention, further contributions of new medicines to combat infectious diseases caused by parasites and viruses are badly needed in developing countries, where these diseases are epidemic, particularly in the tropical regions. For this issue, we spoke with Dr. Yoshihiro Ohmiya and Dr. Koji Furukawa of the National Institute of Advanced Industrial Science and Technology (AIST) and Dr. Toshiya Senda of High Energy Accelerator Research Organization (KEK) about the drug-discovery research on NTDs that this consortium is promoting through collaboration with the engineering field and its technologies.

INFUSING NTDs DRUG-DISCOVERY WITH CUTTING-EDGE ENGINEERING TECHNOLOGY TO PROMOTE BASIC RESEARCH AND CONTRIBUTE TO SOCIETY

Yoshihiro Ohmiya, Ph.D. Director, Biomedical Research Institute, AIST

Koji Furukawa, Ph.D. Senior Research Scientist, Molecular Composite Medicine Research Group, AIST

Toshiya Senda, Ph.D. Director, Structural Biology Research Center, Institute of Materials Structure Science, KEK

Table 1. The 3 steps in the search for compounds through FE Drug-discovery

4Global cooperation among industry, universities, governments, and NPOs to combat NTDs (Neglected Tropical Diseases)

The watchword is “Open Innovation”

The process of Fragment Evolution drug-discovery – at once highly advanced and a sober, painstaking accumulation of efforts

The concentration of advanced technologies from engineering is providing an innovation for NTDs Drug-discovery

12

proteins. By building upon this, Astellas has independently developed a method of drug design called Fragment Evolution (FE) Drug-discovery. This consortium also utilizes FE Drug-discovery.

FE Drug-discovery consists of the 3 steps shown in Table 1. These are posi-tioned as the processes for obtaining lead compounds that can lead to new medicines. These processes are far more advanced than in the past, and they are also methods for efficiently steering drug-discovery.

However, these processes seldom pro-ceed in the sequence of Step 1 → Step 2 → Step 3. In most cases, the same step is repeated many times, or researchers may return from Step 2 to Step 1 and shuttle back and forth between the two steps many times, or return to the search for target proteins to evaluate them, so the work that culminates in obtaining the lead compound that comes to light after Step 3 is a sober, painstaking accumula-tion of efforts.

These processes require advanced engineering technologies such as pro-tein crystallization technology, assay sys-tem construction, and image analysis for three-dimensional structure of proteins, and it is on these points that the cutting-edge technologies of AIST and KEK are focused. Technology components related to the processes of FE Drug-discovery are shown in Fig. 1.

Dr. Yoshihiro Ohmiya of AIST explains the significance of participating in this consortium: “Our greatest mission is to create a base for drug-discovery re-search. What is necessary in order to cre-ate medicines? What kinds of technology should be put to use as we proceed? We are aiming to give back to society by cre-ating this sort of base. In this sense, we think we have been given an opportunity and task of the sort that only comes once in a lifetime.”

The collective efforts of AIST: Research that digs deep and a variety of approaches

AIST is engaged in research and develop-ment in 6 research fields involving such industrial technologies as life science, nanotechnology, and electronics. With 2300 researchers, it is one of Japan’s largest research institutes. Teams span-ning a number of research divisions were formed to participate in this consortium. Among them, Dr. Koji Furukawa plays a central role.

The process of drug-discovery re-search is not easy, even with the use of advanced engineering technologies. Some proteins do not readily crystallize, and in not a few cases, it has been im-possible to predict binding affinity. Dr. Fu-rukawa explains: “Even if the technique is

correct, the actual research is a continued process of trial and error. It is the strong point of AIST that even if an error occurs, we do not immediately give up. Instead, the team digs deeper, making repeated efforts to succeed through trial and error, discussing the problem all the while.”

In addition, AIST’s various cross-cut-ting strengths have been demonstrated to be effective. “For example, we used to count the parasitic protozoa that cause NTDs visually under a microscope, but now having a researcher who specializes in image analysis join the project has pro-vided the advantage of making it possible to use image processing technology to count them. In this way, we can make the most of the various kinds of knowledge and experience that we collectively pos-sess. Even when it comes to problems where we really feel we’re ‘stuck,’ a sug-gestion from a researcher in another field can sometimes lead to a breakthrough” (Dr. Ohmiya).

KEK, supporting the creation of a base for drug-discovery with the most up-to-date facilities

KEK, also known as the “Photon Factory,” is one of Japan’s leading synchrotron ra-diation research facilities. Because KEK’s synchrotron radiation has the character-istics of high intensity and high energy, it

Fig. 1. Process and components of FE Drug-discovery

(Source: Dr. Koji Furukawa)

Source: Astellas Square No.55（2014 Vol.10 No.2）13

makes it possible to perform microcrystal analysis that is difficult with ordinary X-ray structural analysis, as well as high-qual-ity structural analysis at quantities and speeds that were hitherto unimaginable.

In the FE Drug-discovery conducted by this consortium, KEK is mainly re-sponsible for three-dimensional struc-tural analysis of target proteins and the complexes formed by target proteins and fragment hits. Dr. Toshiya Senda ex-plains: “Our role is to provide the most up-to-date facilities for advanced crystal structure analysis. This makes it possible to obtain basic data to form the base for drug-discovery.”

An experimental station (beam line) for crystal structure analysis of proteins de-veloped through joint research with Astel-las has also been introduced, along with a protein crystal exchange system using a Photon Factory Automated Mounting system (PAM) that makes it possible to collect data quickly (Fig. 2).

The idea of contributing to society that lies at the roots of the consortium

Finally, we asked Dr. Senda and Dr. Ohm-iya about the significance of the research conducted by this consortium.

“Listening to the comments of Prof. Kiyoshi Kita, the University of Tokyo, who is summarizing the research for us, I re-alized that NTDs for which no treatment medicines exist can be the cause of so-cial and economic problems as well, and that a lot of people are grappling franti-cally with the problem of NTDs. This gave me a renewed sense of the significance of basic research among these efforts. I would like to contribute to the best of my ability, to help this project proceed smoothly” (Dr. Senda).

“Seeing the high level of activity of the team participating in this consortium and how excited they get about the research gives me a real sense of the benefit that can come of Open Innovation–type proj-ects. Drug-discovery is truly an undertak-

ing that hinges on collective strength. The key to moving forward with this research lies in how to bring about a fusion of all the different technologies that Japan possesses. By all means, I would like to see the technological power we possess channeled into drug-discovery for NTDs” (Dr. Ohmiya).

Dr. Yoshihiro OhmiyaGraduated from Gunma University Graduate School of Medi-cine in 1990. After doing his postdoctoral work, became an assistant professor in the Department of Education at Shizuoka University in 1996 and was appointed head of a research group at AIST. Assumed his present position in 2012.

Dr. Koji FurukawaCompleted graduate program in Biochemistry at Osaka Univer-sity Graduate School of Science in 1993. Assumed his present position in 2010 after working at the Protein Engineering Re-search Institute, Tokyo University of Science, and the AIST Age Axis Bioengineering Research Center.

Dr. Toshiya SendaCompleted the latter half of the doctoral program at Nagaoka University of Technology in 1995. Assumed his present position in 2013 after working at Nagaoka University of Technology and the AIST Biomedicinal Information Research Center.

Fig. 2. Photon Factory Automated Mounting (PAM) system for protein crystal exchange

(Source: Dr. Toshiya Senda)

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The NTDs Drug-discovery Research Consor-tium is using the Open Innovation model to joint research. This means sharing of all the information obtained by the various participat-ing research institutes, which fulfill their own specialized roles in the effort to develop drugs for the 4 NTDs leishmaniasis, Chagas disease, African trypanosomiasis, and dengue fever/dengue hemorrhagic fever. In this consortium, Nagasaki University’s In-stitute of Tropical Medicine is working on the development of treatment drugs caused by trypanosoma protozoa (leishmaniasis, Chagas disease, African trypanosomiasis) as well as dengue fever/dengue hemorrhagic fever.

As the only door to the world for Japan during the period of national isolation from the 17th through 19th centuries, Nagasaki was a por-tal for the influx of Western science and medi-cine. At the same time, it provided an opening for foreign infections to make their way into the country. In fact, “infections” was the first research theme approached by the Medical Training Institute that the Edo Shogunate es-tablished in the Nagasaki city magistrate’s of-fice. This special historical background and a

wealth of accumulated research on infections make Nagasaki an appropriate location for the Nagasaki University’s Institute of Tropi-cal Medicine, Japan’s only one research in-stitute specializing in tropical medicine.

Prof. Kenji Hirayama spoke to us about the Institute’s motivation for participation in the consortium: “We have thought for some time now that we must do something about NTDs, and we had a strong sense of the necessity of corporations, universities, and public organizations joining together to solve this problem. It was at this point that we were approached by Astellas. We decided to participate, with great expec-tations about this timely invitation.” Prof. Kouichi Morita added: “Nagasaki Universi-ty’s Institute of Tropical Medicine is Japan’s in-country research base for promoting scientific research in regions where tropi-cal diseases are epidemic. When we heard that drugs that could be applied to humans may be buried somewhere in Astellas’ own compound library, we thought it would be a good opportunity to utilize our own re-search results.”

Nagasaki University’s Institute of Tropical Medicine has amassed a wealth of informa-tion and research that would have to be called a “treasure trove” of findings on the various pathogens in the world. The consortium will draw upon this strength to verify whether compounds that “ought to work” actually

can be given clinical applications. Specifi-cally, promising compounds will be selected by using anti-protozoan or anti-dengue virus activity as an index for evaluating the many compounds provided by Astellas’ compound library.

This research is divided into 2 main stages. At Stage 1 (primary screening), the protozoa-cidal effect that the compounds have against the parasitic protozoa that cause leishmani-asis, Chagas disease, and African trypanoso-miasis will be measured in vitro. At Stage 2, the effects of the compounds that showed proto-zoacidal activity in the primary screening will be confirmed by observing in vivo parasitemia levels and survival rate.

According to Prof. Hirayama, once try-panosoma protozoa have infected a human being, they exhibit the characteristic of evad-ing the human immune system to continue reproducing within the body while undergo-ing repeated antigenic mutation (Fig.1). It is extremely difficult to arrive at the evaluation of “replication ended” or “eradicated.” At Na-gasaki University, they use the “live imaging” method, which employs full-body images like CT scans and X-ray film, to observe live im-mune response on the host side and measure the organ-specific concentration of infection.

Similarly, in the search for treatment drugs for dengue fever /hemorrhagic dengue fever, a dengue virus infection model is used to measure the efficacy of compounds found to have selective anti-dengue virus activity after in vitro measurements of this, as well as cyto-toxic, activity.

“Humans are the only creatures that are efficiently infected by the dengue virus, lead-ing to illness. For this reason, we are now

In developing countries, there are regions where access to medical care, including pharmaceuticals, remains inadequate. “Neglected tropical dis-eases” (NTDs), for which treatment drugs and other measures have not yet been developed, are a particularly serious problem. A consortium with participation from 6 research institutes representing the industrial, academic, and government sectors of Japan (The University of Tokyo, Tokyo Insti-tute of Technology, Nagasaki University, National Institute of Advanced Industrial Science and Technology (AIST), High Energy Accelerator Research Organization (KEK), and Astellas Pharma Inc.) has joined hands with the global nonprofit organization DNDi to research drug discovery for NTDs in an effort to create treatment drugs for NTDs and contribute to the improvement of global health. For this issue, we spoke with Prof. Kouichi Morita and Prof. Kenji Hirayama about the role of Nagasaki University’s Institute of Tropical Medicine in this consortium and the ultimate goals of the research.

Global collaboration of industry, universities, governments, and NPOs to combat NTDs (Neglected Tropical Diseases)

The watchword is “Open Innovation”

Approaches to drug-discovery research with the 2 pillars of the “search for target candidates” and the “search for compounds”

Kouichi Morita,MD, Ph.D.,Professor, Department of virology, Dean of Institute of Tropical Medicine, Nagasaki University

Nagasaki University’s Institute of Tropical Medicine, one of Japan’s leading research institutes in tropical infections

Evaluating anti-protozoan and anti-dengue virus activity to select promising compounds

5STRIVING TO DEVELOP JAPAN’S FIRST TREATMENT DRUGS FOR NTDS ON THE BASIS OF A WEALTH OF KNOWLEDGE AND EXPERIENCE IN TROPICAL INFECTIONS

Kenji Hirayama,MD, Ph.D., Professor, Department ofimmunogenetics, Former Dean of Institute of Tropical Medicine, Nagasaki University

15

The watchword is “Open Innovation”

at the stage of groping toward establishing a suitable assay system for animal testing” (Prof. Morita).

The mosquitoes that act as disease vectors for dengue virus are Aedes aegypti and Aedes albopictus, and they cause both the febrile dis-ease dengue fever, for which the prognosis is relatively good, as well as the more severe hemorrhagic dengue fever. Dengue virus in-fection is observed in tropical and subtropical zones inhabited by these vector mosquitoes, particularly Southeast Asia, South Asia, South and Central America, Africa, and the countries of the Caribbean Region, but it has also been found in Australia, China, and Taiwan. In Ja-pan, about 200 cases of dengue fever are re-ported annually (Fig. 2). These are all “imported cases,” where someone becomes infected overseas and experiences onset of symp-toms after they return to the home country.

Prof. Morita points out that dengue virus in-

fection is not a problem limited to the tropical zone: “As globalization proceeds and people move from one place to another in increas-ing numbers, there are fears about the in-trusion of dengue virus into the industrially advanced nations. Aedes albopictus, which has the capacity to act as a disease vector for dengue virus, can be found in parts of Ja-pan south of the Tohoku Region, and these mosquitoes become active in the summer season. If Aedes aegypti infected with den-gue virus should find their way into Japan, it would become a big problem.”

Actually, in August of 2013, it was re-ported that German tourists returning from Japan became sick with dengue virus. The time has come when we must bear in mind the possibility of dengue virus infection oc-curring here in Japan.

Both of these experts have great hopes for what the consortium can accomplish. “The fact that this drug-discovery research has the

participation of Astellas, a Japanese pharma-ceutical manufacturer, gives me a real sense that NTDs drugs discovered in Japan have taken one step closer to being a reality” (Prof. Hirayama). “In the process of searching for compounds, we are aiming for a synergy coming from the fusion of two elements: IT (information technology) Drug-discovery and FE Drug-discovery. This first of these utilizes our knowledge and techniques along with cutting-edge computational science and su-percomputers. FE, of ‘Fragment Evolution’ Drug-discovery, is Astellas’ own technique for designing lead compounds” (Prof. Morita).

Prof. Hirayama told us that it is highly possible that even primary care physicians will have op-portunities to encounter NTDs. “For example, with Chagas disease, we sometimes see cardiac disorders or megacolon. When such symptoms are observed, physicians are go-ing to need to take the stance of adequately questioning the patient about disease history and place of origin, and then examine the pa-tient carefully, bearing in mind the possibility of Chagas disease. It will also be important to make efforts to prevent the spread of infec-tion, such as watching out for maternal-fetal transmission during pregnancy or at the time of delivery.”

Prof. Morita concludes: “The first U.S. case of infection with West Nile virus was reported in 1999 by an internist in New York City. This internist deserves great credit for discovering this infection, which has the potential to be-come critical and against which no specific medicine exists. In Japan as well, we have reached an era where the primary care physi-cians at the front lines of routine practice will be expected to do their part to combat NTDs. We want them to realize that NTDs are encroach-ing nearer and be sure to consult with public health centers or specialized research insti-tutes when they encounter suspicious cases.”

Prof. Kouichi MoritaGraduated from Nagasaki University School of Medicine in 1981. Appointed professor at the same university in 2001 after serving as a research assistant at the Nagasaki University Insti-tute of Tropical Medicine, assistant at the University of Medicine and Dentistry of New Jersey in the United States, Manager of the Infection Control Section of the World Health Organization (WHO) West Pacific Region Office, and Instructor at the Naga-saki University's Institute of Tropical Medicine. Assumed pres-ent position in 2013.

Prof. Kenji HirayamaGraduated from Faculty of Medicine, Tokyo Medical and Dental University in 1981. Became a professor at Nagasaki Univer-sity's Institute of Tropical Medicine in 2001 after serving as an assistant at Medical Institute of Bioregulation, Kyushu Univer-sity, a lecturer at St. Marianna University School of Medicine, a researcher at Harvard University in the United States, and a professor at Saitama Medical University Faculty of Medicine. Served as Dean of Nagasaki University's Institute of Tropical Medicine from 2007 to 2011.

Fig. 2. Number of confirmed dengue fever /hemorrhagic dengue fever patients in Japan 　　 (as of Dec. 31, 2013)

(Source: National Institute of Infectious Diseases Dengue Virus Infection Information http://www0.nih.go.jp/vir1/NVL/dengue.htm)

Source: Astellas Square No.55（2014 Vol.10 No.2）

Toward an age when even primary care physicians play a role in combating NTDs

Fig. 1. Antigenic mutation of the trypanosoma protozoa

(Source: Museum of Tropical Medicine, Nagasaki University)

The different colors in the graph show the antigenic mutations of the protozoa. With the production of an-tibodies to the surface antigens of the proliferating trypanosoma protozoa, the number of protozoa initially decreases, but protozoa with different antigens begin to multiply by binary fission. The cycle of antibody production and reduction in the protozoa count is then repeated. Since it is possible for a single protozoan to generate several hundred variations of its surface antigens, it is possible for the trypanosoma protozoa to evade the human immune system and repeatedly replicate in the bloodstream.

All have been imported cases. In 2003, the number of overseas travelers decreased because of the global epidemic of Serious Acute Respiratory Syndrome (SARS). From 2012 onward, reports of hemorrhagic dengue fever infections have become conspicuous (Figures for 2013 are tentative).

Aiming to develop Japan’s first treatment drugs for NTDs through a synergy of cutting-edge approaches

Dengue virus / hemorrhagic dengue virus –Not just a problemfor the tropics any more

16

Among the 17 NTDs that are the focus of attention by the World Health Organization (WHO), the 4 diseases of leishmaniasis, Chagas disease, African trypanosomiasis, and dengue fever/dengue hemorrhagic fever are the targets of the NTDs Drug-discovery Research Consortium’s efforts to discover new treatment drugs.

The special feature of this consortium is that it brings together top Japanese re-search institutes representing the indus-trial, academic, and government sectors (The University of Tokyo, Tokyo Institute of Technology, Nagasaki University, National Institute of Advanced Industrial Science and Technology (AIST), High Energy Accel-erator Research Organization (KEK), and Astellas.) in an Open Innovation research structure. It has also partnered with interna-tional nonprofit organization DNDi on the 3 diseases caused by trypanosoma protozoa and develop our activities.

Organizations known as “Product Develop-ment Partnerships” (PDPs) play a major role in the research, development, and supply of new treatment drugs, vaccines, and diag-nostic drugs for infections in the developing countries. PDPs are nonprofit organizations specializing in specific diseases, and they coordinate joint research with corporations,

governments, and research institutes, and also support product development. Today PDPs shoulder important roles at each step of the way from drug-discovery research to clinical development and distribution.

About 20 PDPs are presently active, chiefly in the EU and US, and DNDi is one of them. Thus far, it has succeeded in pro-viding 6 pharmaceutical products, such as a medical compound to treat malaria and a pediatric formulation of a drug for Chagas disease, by improving and combining exist-ing drugs.

DNDi was founded in 2003. A portion of the Nobel Peace Prize awarded to the international humanitarian organization “Doctors Without Borders” was used to fund its establishment. Its headquarters is in Switzerland, and it has bases of activity in 7 places throughout the world (Fig.1). The Japan office began its activities simultane-ously with the inauguration of DNDi.

Ms. Fumiko Hirabayashi, who has served as Japan representative since the establish-ment of the Japan office, explained that the role of DNDi is divided into 3 main parts. “First, DNDi works to develop new drugs for NTDs; second, it works to strengthen and develop the capabilities of people involved in medical care and R&D in the affected coun-tries; and thirdly, it is involved in information transmission and advocacy (policy propos-als) to various national governments.”

The Japan office, which shares the same philosophy as DNDi, acquired corporate sta-tus in November of 2009, becoming specified nonprofit corporation “DNDi Japan.” Aim-ing to strengthen its alliances with Japanese partners, it is supporting projects that are col-laborations among DNDi, related international organizations, and Japanese pharmaceutical companies, universities, research institutes, and governmental organizations.

Japan’s first consortium of universities, gov-ernments, and industry to discover drugs for NTDs was formed in 2012. Its alliance with DNDi began the same year.

Ms. Hirabayashi sees this consortium as a group of specialists with a very high level of expertise: “We could say it is an extremely valuable opportunity to have people from Japan’s top-level research institutes come together to work on drug-discovery. The in-novative techniques of IT drug-discovery and Fragment Evolution (FE) drug-discovery are being employed. What’s more, this is the only Japanese approach to NTD drug research that takes the form of a ‘consortium.’”

In addition to concrete knowledge on NTDs and patients, DNDi possesses an internation-al network that makes this partnership indis-pensable to the consortium. Ms. Hirabayashi described the role of DNDi as follows: “We would like to share the experience with the target diseases that DNDi has accumulated thus far with all of the various research insti-tutes that are participating in this consortium. Moreover, we would like to provide advice on the selection of target proteins and lend our support to the in vitro and in vivo screening, as well as the search for fragment hits.”

Ms. Hirabayashi introduced the topic of the

Many of the infectious diseases that are epidemic in the tropical regions of developing countries are referred to as “neglected tropical diseases (NTDs)” because insufficient measures have been taken to prevent and treat them. In the previous 5 installments in this series, we have introduced the activities of the NTDs Drug-discovery Research Consortium, which aims to discover treatment drugs for NTDs. This time, we spoke with Ms. Fumiko Hirabayashi, Japan representative of DNDi (Drugs for Neglected Diseases initiative), about the activities and role of this organization, which has been deploying its activities in collaboration with the consortium. We conclude by asking Dr. Wataru Uchida, Senior Vice President and President, Drug Discovery Research at Astellas about the significance and ultimate goals of this consortium.

6Global collaboration of industry, universities, governments, and NPOs to combat NTDs (Neglected Tropical Diseases)

The watchword is “Open Innovation”

DNDi is one of the pharmaceutical development partnershipsThe aim is to develop treatment drugs for NTDs

Over 1 billion people infected in the worldNTDs are an important global health issue

Fumiko Hirabayashi, Japan representative of international nonprofit organization DNDi / Secretary General of specified nonprofit corporation DNDi Japan

Partnership with the consortium: Engaged in development, planning, and strategy together

The world has great expectations ofJapan’s R&D capabilities.We would like to bringnew treatment drugsto the patients even one day earlier

FOCUSING WISDOM AND TECHNOLOGY ON NTDS DRUG-DISCOVERY TO BRING TREATMENT DRUGS TO WAITING PATIENTS THROUGHOUT THE WORLD

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world’s expectations of Japan: “It is widely known that Japan has contributed much to global research on infectious diseases thus far. For this reason, people have confidence in – and great expectations for – the R&D capabilities of Japan’s research institutes and pharmaceutical companies. When it comes to NTDs drug-discovery as well, not only the developing countries but the world at large has voiced the expectation that ‘surely Japan will be able to do something.’”

Ms. Hirabayashi went on: “I think that Japan’s research institutes and pharma-ceutical companies really do have the R&D capabilities to respond to these global ex-pectations. We at DNDi would also like to do our best to ensure that strength is uti-lized more fully to solve the health problems that the world confronts.”

Finally, Ms. Hirabayashi expressed her earnest hopes for the project: “There are many patients suffering from NTDs on this earth, and they are hoping for the advent of new treatment drugs. We would like to get new drugs to these patients even one day earlier. With that hope, we will continue to work together with the consortium in the future as well.”

“We are tackling this project with a spirit of challenge to respond to unmet medical needs in the strong sense that we want to make a solid contribution to solv-ing global health prob-lems.” Wataru Uchida, who leads Astellas Pharma’s Drug Discov-

ery Research, spoke about the stance of As-tellas toward this consortium.

Each of the institutions participating in this consortium has its own individual strengths, whether they be cutting-edge scientific infor-mation on pathology, IT technology for swiftly establishing relationships in a large mass of data, the unique drug design method FE Drug-discovery or a global medical network.

Generally in drug-discovery research, it is not uncommon for even the name of the dis-ease that is the target of research and devel-opment to be withheld, but this consortium takes an Open Innovation approach, sharing not only the name of the target disease but also information on drug-discovery research within the consortium.

“Success in drug-discovery hinges on collec-tive strength. This consortium has fused the researcher’s passion for research with the top-level findings and technology that Ja-pan has to offer. As a result, we have suc-ceeded in narrowing down and prioritizing the list of target proteins for leishmaniasis, Chagas disease, African trypanosomiasis – which have the same causative parasite – in the span of about one year since the start of research. On dengue fever and hemor-rhagic dengue fever as well, research on the establishment of an appropriate assay system in animals is making progress.

“If Astellas had taken on this project sin-gle-handedly, we probably would not have been able to proceed with that ‘speed.’” Uchida then turned to the consortium’s conception of the ultimate goal of NTDs drug research as it has been tackled from this unprecedented approach.

One of the principles of Astellas’ busi-ness philosophy is to “Contribute toward improving the health of people around the world through the provision of innovative and reliable pharmaceutical products.” The NTDs drug-discovery research conducted by this consortium could indeed be said to embody this principle. Dr. Uchida con-cluded by saying a few words about his aspirations and hopes for the future: “Re-sponse to this consortium has been great, both within the company and from outside, and we have been greatly encouraged by that. We want to succeed with NTDs drug-discovery in this consortium without fail, and we would like to make the best use of this experience in future drug-discovery re-search as well.”

Fig.1 Bases of DNDi and network

(Source: International nonprofit organization DNDi)

Source: Astellas Square No.55（2014 Vol.10 No.2）

Responding to unmet medical needs with Open Innovation joint research

Dr. Wataru Uchida,Ph,D., Senior Vice President and President, Drug Discovery Research

Ms. Fumiko Hirabayashi

Graduated from Hoshi University. After working for a

foreign-affiliated pharmaceutical company, served as

a pharmacist at a hospital in Thailand and a coordina-

tor for an investment company in Hong Kong. In 2000,

assumed charge of the essential drugs campaign of

“Doctors Without Borders.” Later participated in the

HIV/AIDs project in Uganda. Assumed present posi-

tion in 2004.

Success in drug-discovery hinges on “collective strength”The fusion of top-level findings and technology leads to results

18

Schistosomiasis (also known as bilhar-zia) remains one of the most significant neglected tropical diseases. It affects 78 countries, with 800 million people at risk and an estimated 200 million infected people. Schistosomiasis occurs primarily in developing countries with limited access to safe drinking water and adequate sani-

tation. If not treated properly, the disease can lead to anemia, stunting and reduced learning ability and consequently seriously impacting the quality of life of patients, in particular children. The risk of infection is particularly high for young children, who are likely to come into contact with water con-taminated with schistosomes in their daily lives. Although rarely fatal, due to its recur-rent nature it manifests itself as a persistent chronic disorder in endemic countries, and represents an important health burden, es-pecially in Africa where more than 90% of the infections occur.

A standard recommended praziquan-tel treatment is already available in oral tablets as an effective standard treat-ment drug for schistosomiasis in adults and school-age children, but a pediatric formulation suitable for treating younger children (below 6 years) is lacking. The schistosomes can be eliminated in in-fected patients by having them take the drug once or twice a year. However, the commercial praziquantel Cesol 600 mg tablet is too large, measuring 22 mm x 8.5 mm, for preshool children to swal-low. Moreover, the active ingredient of praziquantel has a distinctive bitter taste that even adults feel unconformable If the tablets are crushed into powder so that small children can easily take the medi-cine, the children will end up spitting it out because it tastes so bitter. Treatment thus comes up against a major stumbling block: there is currently no clinical data for children under the age of six and no way to eradicate the causative parasite if the patient cannot even take the medi-cine.

ediatric Praziquantel Consortium established to

provide pediatric formulations P

A public-private partnership established in 2012, the international non-profit Pediatric Praziquantel Consortium, is currently work-ing to address the unmet medical needs of the preschool age group. This age group is especially vulnerable, and accounts for an estimated 10% of the global population already infected or at risk. Strong interna-tional partners are now cooperating and contributing their expertise to develop a pediatric tablet with a type of praziquantel that works even in small doses and tastes better than the original. One of the roles of Astellas in this con-sortium is to develop pediatric formulations based on its expertise in innovative formu-lation development technologies. This role was entrusted to the Pharmaceutical Re-search and Technology Labs (PRTL) led by Dr. Kazuhiro Sako. “Even if a drug itself may have phar-macological effect, without formulation technology it is merely a compound (drug substance) that could even be poisonous or have no benefit depending on how it is used. That drug substance is finally trans-formed into a safe and effective drug prod-uct that can be administered to humans by creating an appropriate finished dosage form through pharmaceutical technologies.

It is the job of the PRTL to create drug products that are effective and easy for pa-tients to take. This involves a number of as-pects: reducing disadvantages associated

The Pediatric Praziquantel Consortium was founded in July 2012 with the objective to develop and register a new praziquantel pediatric

formulation for the treatment of schistosomiasis in preschool-age children, including infants and toddlers. Astellas has been a core member

in this not-for-profit partnership from establishment and has contributed by providing our expertise and technology in the area of pediatric

formulation development and clinical development. Dr. Kazuhiro Sako, former Consortium Board member and Vice President Pharmaceutical

Research and Technology Labs at Astellas, shares his experience in the Consortium.

THE CHALLENGE OF DEVELOPING A NEW PEDIATRIC FORMULATION TO TREAT SCHISTOSOMIASIS– Japanese formulation technology to bring smiles and a bright future to children in endemic countries –

Eliminating Schistosomiasis

An infectious disease caused by adult worms of the

blood parasite Schistosoma, which infect the veins

of the digestive tract and urogenital system. Larvae

invade the skin of children who have played, swum,

or walked in contaminated water, and they grow into

adult worms inside the body. The acute symptom

is dermatitis, and within a few weeks, the infected

child will develop pyrexia, chills, nausea, abdominal

pain, diarrhea, malaise, and muscle pain. The adult

worms are estimated to live for 3 to 37 years.

Schistosomiasis

Microscopically-obsered Schistosome using IFA method (x78, Schistosomiasis mansori)©CDC/Marianna Wilson

he present status ofschistosomiasis in Africa

– Many children lose their lives because there is no pediatric formulation –

T

19

with drug substances, such as their partic-ular (or unpleasant) taste and smell; giving them an easy-to-swallow size and shape; minimizing frequency of doses that must be taken each day; and designing to suppress adverse reactions. We pride ourselves on having formulation technology that is top level even on a global scale.”

After these introductory remarks, Sako reflected back on the state of mind that led his team to be involved in this project: “We are in the opinion that there is no dos-age form that children under the age of six could take, it is the same as no treatment for this age group of children. If we could only create a drug product that children could easily take by use of our pharma-ceutical technologies, then many children could be saved from schistosomiasis. This kind of thinking motivated us to challenge developing a pediatric formulation of pra-ziquantel.”

The development team was composed of volunteering researchers in Astellas PRTL.After about 2 years –with many ups and downs in progress– a pediatric formulation of praziquantel that could be administered to and taken by infants and small children aged 3 months and older was finally developed (Photo 1).

The key characteristics of this formula-tion are (1) smaller tablet size, (2) orally dis-integrating, and (3) reduction of bitterness. The tablets are at about one-fourth the size of commercial praziquantel tablets, and have the orally disintegrating property so that they can be taken even without water. Moreover, bitterness cancelling technology utlizing additives could lead to less bitter-ness, the team hopes to have succeeded in greatly reducing the bitterness of the active ingredient of praziquantel.

There were a number of barriers to over-come in the development of the pediatric formulation of praziquantel. In order to fa-cilitate global market access of this pediat-ric drug product and provide it at an afford-able price especially to endemic countries, it was necessary to produce at low costs and create a formulation that could be produced by conventional processes (manufacturing technologies) as simple as possible. Moreover, the tablets require ap-propriate shelf-life and need to be resistant to the instability that can occur in the hot and humid environment of tropical regions. The candidate tablet formulation was cre-ated after repeated tests in order to with-stand these challenging requirements.

“From the start of development, we found ourselves coming up against any number of barriers that had to be over-come, but our motivation has been highly maintained because we could imagine the happy faces of the children once we would have removed these obstacles. That made it possible for us to keep on trying while enjoying the development process.” This great enthusiasm of Sako spread to each member of the development team. All of the team members are cheerful and lively, and on one thing they are all in unison: “We were excited about what we were doing, and we were able to continue with the re-search because it was worth doing.”

Clinical studies with the new pediatric formulation will begin at the end of 2014. Sako expects that once a certain amount

of data can be accumulat-ed and verified in the clini-cal studies, the day will not be that far off when this new pediatric formu-lation can be delivered to the children of endemic countries.

Actually, reaching the stage of clinical studies in about 2 years from the inception of this consor-tium in 2012 is quite rapid progress. The greatest reason for this success was the great contribution of all partners and the fact

that the drug substance already existed. If the pediatric formulation can be delivered to children requiring treatment even a little earlier, many lives will be saved. In this sense, the stage on which the pharma-ceutical technology contributes to improv-ing access to healthcare has broadened even further.

Since the efforts of this consortium are non-profit activities, Sako and the mem-bers of the develop-ment team engaged in research on the formulation develop-

ment of praziquantel on a volunteer basis while carrying out their usual duties in par-allel. One might expect there would be few people who would be willing to undertake work that imposed on them a time burden and brought no financial return.

In response to these doubts, Sako re-flected that he found willing volunteering researchers as soon as he attempted to re-cruit development team members from the PRTL. “As their motivation, the researchers like to be at service to the patients. The work of this consortium has been a valu-able experience to get a direct sense on how, by using their technologies and sci-ence, patients can be helped.”

Still, Sako admits that he did his best to create an atmosphere under which every-one would perceive the value of their job. “I told them, ‘Our strength may save the lives of hundreds of thousands of children in Afri-ca,’ he recalls. ‘The pharmaceutical technol-ogy to develop a pediatric formulation may

ith the pharmaceutical technology, a pediatric for-

mula that children could easily take was developed

W

ur mission was to create a therapeutic drug for schisto-

somiasis that could be provided to children as soon as possible

O

he joy of trying to overcome barriers

– Because they could imagine the happy faces of the patients up ahead –

T

e want to be of use to the patients”

That motivation led to a new circle of contributions

W“

Dr. Kazuhiro Sako

Photo 1. The pediatric formulation of praziquantel developed by this consortium (top) and a conventional praziqu-antel tablet (bottom)

20

benefit the children of Japan in return.’”With this encouragement, the entire de-

velopment team came to share in the signif-icance and joy of being involved in the work of this consortium, and before they knew it, all the members began to feel a sense of excitement about working on development.

In his closing remarks, Sako explained that “Since development of formulations re-

quires a sustained effort, having that work highly rated by those around you or outside your organization also leads to motivation. This creates a virtuous cycle that can give birth to the next result. For this reason, I am continually appealing to people outside our company to look at what we are doing in this area.”

In fact, the fruits of this consortium have

earned recognition by various international organizations, which have led to funding new activities. There is much potential for Japanese pharmaceutical technology and innovation to play a more direct role in the fight against neglected tropical diseases in the future.

AbbreviationsTI Pharma: Top Institute Pharma

Swiss TPH: Swiss Tropical and Public Health Institute

Members of the Pediatric Praziquantel Formulation Development Team participating from the Pharmaceutical Research and Technol-ogy Labs of Astellas Pharma’s Technology Department (from left, Yumiko Suda, Takehiko Yasuji, Kazuhiro Sako, Hiroaki Tasaki, Seiji Takae, Atsushi Sakurai)

THE CHALLENGE OF DEVELOPINGA NEW PEDIATRIC FORMULATION TOTREAT SCHISTOSOMIASIS

Eliminating Schistosomiasis

The work on developing a pediatric formulation of praziquantel that I participated in as a project team leader of the Pharmaceutical Re-search and Technology Labs’ development team was a series of encounters with the unknown that I ordinarily could never have ex-perienced. In fact, we investigated and developed another dosage form in advance of the current candidate formulation but we had to take it back to the drawing board when we finally realized it was “not optimal for infants.” The technical transfer to Brazil was also first experience to me.

The thing that we extensively tried in the development team was open and proactive communications. We did our best to exchange opinions frankly.

Although this consortium was formed from a multinational organizations with dif-ferent languages and cultures, it is held together by the common and unshakable aspiration to “bring medicine to the children of Africa.” This aspiration continuously and strongly supported this project from behind and led to the resolution of many difficulties.

I am now working outside Japan with Astellas US Technolo-gies in the United States, but my experience with this consortium was a treasure of the kind that knows no substitute in the life of a researcher.

Dr. Hiroyuki Kojima

From the experience of participating in the project

What is the Pediatric Praziquantel Consortium?

The Pediatric Praziquantel Consortium is an international, non-profit, public-private

partnership in schistosomiasis, supported by world leading experts in tropical parasitic

infectious diseases. The Consortium’s goal is to develop and launch a suitable pediatric

formulation of the ‘gold standard’ drug treatment (PZQ) for children under 6 years old.

Significant progress has already been made towards developing a PZQ formulation that

can be readily administered to the pre-school age children (3 months to 6 years). In this

consortium of highly driven partners, each of the members of the consortium is drawing

upon its expertise to work toward the realization of these goals. The 4 original members

that participated in the planning of the consortium at its inception were Merck KGaA of Germany, which is responsible for leadership of the

project; Astellas Pharma; international non-profit organization TI Pharma, which is the coordinator; and the research institute Swiss TPH.

Later 2 more joined: Farmanguinhos, a pharmaceutical laboratory linked with the Oswaldo Cruz Foundation under the Brazilian Ministry

of Health, and Simcyp, a company that specializes in modeling and simulation of pharmacokinetics. Phase I Clinical studies in humans in

Africa will begin in 2014. This consortium is supported by grant contributions awarded by the Bill and Melinda Gates Foundation in 2013

and by the Global Health Innovative Technology (GHIT) Fund in 2014.

21

Programme will treat 1,200 women withlife changing surgery and increase surgical capacity

Obstetric fistula sufferers are too often

subject to severe social stigma due to

odour which is constant and humiliat-

ing, often driving the patients’ family,

friends and neighbours away. Stigma-

tised, these women are also often de-

nied access to education and employ-

ment and left to live lives of isolation

and poverty.

Ken Jones, President & CEO of As-

tellas Pharma EMEA, commented, “Ac-

tion on Fistula tackles a significant need

for treatment in urology, where we have

a strong heritage. Through our flagship

corporate giving programme we want

to help treat more women living with this

devastating condition. Critically, the pro-

gramme will build capacity through sur-

gical training so that even more women

can be treated in the future.”

Kate Grant, CEO, Fistula Foundation,

responded,

“There is an enormous need for fistula

treatment in Kenya and we can’t face

this challenge alone. We’re honoured to

be working with Astellas to help end the

suffering of women across the country. ”

The Action on Fistula programme

will help provide the vital treatment

these women need and deserve to

live happy, fulfilled lives. This generous

support will also help us train more

surgeons to deliver high quality treat-

ment, enabling many more women to

be treated in the future.

WHY

Astellas is supporting a groundbreaking

programme, Action on Fistula, an initia-

tive led by the charity Fistula Founda-

tion from 2014.

An obstetric fistula is a hole between

the vagina and rectum or bladder that

is caused by prolonged obstructed la-

bour when emergency care is unavail-

able, causing either fecal or urinary in-

continence or both conditions. Whilst

virtually eradicated in developed coun-

tries, the United Nations Population

Fund (UNFPA) estimates 3,000 new

cases of obstetric fistula occur annu-

ally in Kenya, with approximately one to

two fistulas for every 1,000 deliveries.

Funding of €1.5 million over 3 years

by Astellas to Fistula Foundation

will transform the lives of more than

1,200 women in Kenya living with ob-

stetric fistula.

WHAT

Funding will provide support to in-

crease by 100% the number of fistula

surgeons trained utilising the Interna-

tional Federation of Gynaecology and

Obstetrics (FIGO) Competency Based

Training Programme in Kenya and sig-

nificantly boost the number of surger-

ies that take place. A Fistula Treatment

Network across Kenya will also be cre-

ated and a major outreach programme

funded with community workers iden-

tifying and encouraging patients to ac-

cess available treatment.

HOW

For more information about the programme visit

http://www.astellas.eu/action-on-fistula/index.html

http://www.astellas.eu/ action-on-fistula

22

Astellas Leanings/Experience◦ Served as an opportunity to learn about clinical research in a part of the world/country we have not yet been actively

engaged for Development

◦Led to understanding that science/medical needs can be “universal language” beyond borders and we “learned” as much as we ‘taught’

More on the TDR Career Development Fellowship

http://www.who.int/tdr/capacity/strengthening/career_development/en/

WHO TDR-IFPMA FELLOWSHIP PROGRAMIN RESEARCH AND TRAINING IN TROPICAL DISEASES

Providing Training Opportunitiesfor Research Fellows from Developing Countries The objective of the fellowship, officially

known as the TDR* Clinical Research

and Development Career Development

Fellowship Program, is to place candi-

dates within the industry to develop and

promote high-quality clinical research

and development in disease-endemic

countries. Fellows work to enhance

product development capacity for treat-

ment of infectious diseases, which have

a high impact in developing countries.

This career development fellowship is

supported by the Bill and Melinda Gates

Foundation and promotes high quality

research in diseases endemic countries

through the experiences gained by the

clinical fellows via this pharmaceuti-

cal company/IFPMA partnership. The

Industry gains opportunities through

which it is possible to enhance product

development capacity for diagnostics,

drugs and vaccines against infectious

diseases that disproportionately impact

developing countries.

While Astellas does not have a broad

R&D organization focusing on develop-

ment of products for treatment or pre-

ventions of HIV, the Astellas portfolio

did allow synergy with the program. Dr

Marukutira focused primarily on working

with the micafungin pediatric and the

isavuconazole teams, both in late stage

development (Phase 3/3b). Therefore,

he was able to consider related and/or

multi-factorial health problems for HIV

patients and the impact clinical research

has on diseases of endemic countries

in the pediatric patients. The fellowship

served as an opportunity for Astellas to

learn about clinical research in a part of

the world in which Astellas have not yet

been actively engaged in research and

development.

Astellas has continued its support to

host another TDR fellow from Ethiopia

during 2013-2014.

*TDR: Special Programme for Research and Training in Tropical Diseases

“Not only did I master aspects of drug development from pre-clinical through to

phase IV studies, I also developed as a professional. For my colleagues it was always

a big question of what type of training I am doing in a pharmaceutical company, yet

after interacting again we all agree that it was worth the time. The pharmaceutical

industry plays a significant role in what we as clinicians think about, do and use as

therapeutic interventions for our patients.”

Dr. Tafireyi Marukutira,(TDR fellow 2011-2012)Research medical officerat the Botswana-Baylor Children’sClinical Center of Excellencein Botswana, Africa

As part of our CSR (Corporate Social Responsibility) initiative,Astellas sponsored a clinical fellowship program in partnership with the InternationalFederation of Pharmaceutical Manufacturers and Associations (IFPMA),the World Health Organization (WHO), and the Bill and Melinda Gates Foundation since 2011.

23

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Published November 2014

2-5-1, Nihonbashi-Honcho, Chuo-Ku, Tokyo 103-8411, Japan

Tel. +81-3-3244-3000 (pilot number)

Astellas Pharma Inc., based in Tokyo, Japan, is a pharmaceutical company

dedicated to improving the health of people around the world by providing

innovative and reliable pharmaceutical products. Astellas has approximately

18,000 employees worldwide. The organization is committed to becoming

a global category leader in Urology, Immunology (including Transplantation)

and Infectious diseases, Oncology, Neuroscience and DM Complications and

Kidney diseases.

In addition to the “Access to Health” initiatives introduced in this pamphlet, the

Astellas website includes contents such as our fields of CSR-based manage-

ment, etc.

http://www.astellas.com/en/csr/

Also please visit Astellas corporate website:

http://www.astellas.com/en/

About Astellas Pharma Inc.

ASTELLAS’ RAISON D’ETRE AND

ACCESS TO HEALTH INITIATIVES

GLOBAL COOPERATION AMONG

INDUSTRY, UNIVERSITIES, GOVERN-

MENTS, AND NPOS TO COMBAT NTDS

(NEGLECTED TROPICAL DISEASES)

1 AN ALL-JAPAN EFFORT TO DISCOVER

TREATMENT MEDICINES FOR NTDS

2 FROM JAPAN TO THE WORLD:

PHARMACEUTICALS TO TREAT

INFECTIOUS DISEASES AT THE

GLOBAL LEVEL

3 AIMING TO REALIZE SUPERCOM-

PUTER DRUG-DISCOVERY MAKING

FULL USE OF CUTTING-EDGE IT

TECHNOLOGY

4 INFUSING NTDs DRUG-DISCOVERY

WITH CUTTING-EDGE ENGINEERING

TECHNOLOGY TO PROMOTE BASIC

RESEARCH AND CONTRIBUTE TO

SOCIETY

5 STRIVING TO DEVELOP JAPAN’S

FIRST TREATMENT DRUGS FOR

NTDS ON THE BASIS OF A WEALTH

OF KNOWLEDGE AND EXPERIENCE

IN TROPICAL INFECTIONS

6 FOCUSING WISDOM AND TECHNOL-

OGY ON NTDS DRUG-DISCOVERY TO

BRING TREATMENT DRUGS TO WAIT-

ING PATIENTS THROUGHOUT THE

WORLD

ELIMINATING SCHISTOSOMIASIS

THE CHALLENGE OF DEVELOPING A

NEW PEDIATRIC FORMULATION TO

TREAT SCHISTOSOMIASIS

ACTION ON FISTULA

WHO TDR-IFPMA FELLOWSHIP PRO-

GRAM IN RESEARCH AND TRAINING

IN TROPICAL DISEASES

Contents