CHANGING LIVES.

CONNECTING PEOPLE,

Headquarters

Yomiuri Shimbun Bldg.1-7-1 Otemachi,Chiyoda-ku,Tokyo, 100-0004,Japan

2019/2020 Edition

Tel: +81 (0)3-6870-2200Fax: +81 (0)3-6870-2241

www.amed.go.jp/en/

2019/2020

WE ARE AMED,THE JAPAN AGENCY

FOR MEDICAL RESEARCHAND DEVELOPMENT.

Making life better for patients around the world today.

As medicine continues to advance rapidly, the development of new approaches to diagnostics

and therapeutics that contribute to human health is vital.

AMED was established in April 2015 to catalyze the process of medical innovation and overcome the barriers between sectors, connecting talented individuals to accelerate medical research and

development. Since then, we have made significant gains in the fight against many

diseases.

As part of the Initiative on Rare and Undiagnosed Diseases (IRUD), genetic analysis systems are more accessible than ever. This is thanks to data sharing among physicians and scientists in more than 400 hospitals in Japan – a program pioneered by AMED. More than 1,000 undiagnosed patients who suffered from diagnostic odyssey over many years were diagnosed within 6 months after their registration to the initiative. The IRUD Exchange Database is contributing to case matching not only in Japan but also with foreign patients, as AMED empowers global networks for data sharing.

AMED also led the ASIA-first driver project of Global Alliance for Genomics and Health (GA4GH) – an international organization aiming to advance medical care and medicine through international genome data sharing.

“Our mission is to fast-track medical research and development.”

While our progress is encouraging, we understand the challenges we face cannot be overcome without global collaboration. To date, we have entered into Memorandum of Cooperation agreements with several of our counterparts: NIH in the U.S., MRC in the U.K., A*STAR in Singapore, SEIDI in Spain, the Ministry of Health in Lithuania and NHMRC in Australia.

In addition to rare disease research, we are also pursuing enhanced data sharing of clinical imagery across multiple fields, including pathology, endoscopy and CT scanning. Our aim is to develop diagnostic AI and contribute to the collaborative consortium of Japan Excellence for Diagnostic Imaging (JEDI).

Many challenges lie ahead as we work to improve health in Japan and around the world. However, through close cooperation with the global medical community, we can deliver the best medicine and change lives for the better.

Makoto Suematsu, M.D., Ph.D.President, AMED

0201

JAPANESEGOVERNMENT MINISTRIES

Ministries establish mid/long-term goals based on government policy and set budgets accordingly.

RESEARCHERS AND INSTITUTES

FUNDING ALLOCATION BY AMED

In addition to funding allocation, AMED networks academia and industry in order to accelerate

medical discovery.

HEADQUARTERS FORHEALTHCARE POLICY (HHP)

Japanese government establishes top-level policy for medical research and development.

AMED allocates funding to support researchers, providing a single point of contact from initial research to

outcomes that benefit society.

In line with government policy, we provide a single window of support and funding for research projects.

A New Approach to MedicalResearch & Development

Who We AreThe Japan Agency for Medical Research and Development (AMED) was established in 2015 for the advancement of medical discoveries that make life better for everyone.

Based on effective partnerships and innovative collaboration, we pursue medical breakthroughs through an approach consisting of three vital components:

People are at the heart of everything we do. We support, connect and promote, helping researchers to make incredible discoveries and change the lives of patients around the globe.

SUPPORTFunding medical studies and research facilities

CONNECTLinking organizations, institutions and researchers

PROMOTEPromoting the practical application of beneficial research outcomes

1

2

3

What We DoWorking beneath the Prime Minister’s Cabinet and national ministries, we provide a single window for researchers and institutions seeking funding for medical research and development.

Prior to our establishment, researchers were required to request funding from several ministries, depending on the phase of their studies. Now, we provide streamlined, consistent support from initial investigations to practical application of new medicines and treatments in the real world.

We also work to connect the most qualified practitioners, medical institutions and private-sector organizations, at home and abroad, to give clinical studies the best possible chance of succeeding.

Once studies are completed, we focus our resources on promoting new medicines and treatments to ensure they get to the people who need them most.

When it comes to medical innovation, we are with you every step of the way.

MINISTRY OFEDUCATION, CULTURE, SPORTS,

SCIENCE AND TECHNOLOGY

CABINET SECRETARIAT, OFFICE OF HEALTHCARE POLICY

MINISTRY OFECONOMY, TRADE AND

INDUSTRY

MINISTRY OFHEALTH, LABOUR AND

WELFARE

03 04

Management andEvaluation FrameworkTo ensure the best chance of beneficial research outcomes, we assign program directors (PD) to each of our nine key fields, and program supervisors (PS) and program officers (PO) to each program within the field.

These individuals have distinguished academic backgrounds and

are handpicked for their expertise in a specific area of research. They work closely to grasp the situation and challenges in their field in order to comprehensively evaluate research proposals and provide expert program coordination. Their ultimate goal is to manage research and advise researchers to make processes run more smoothly and ensure better results.

PROGRAM MANAGEMENT FRAMEWORK

Primary roles of PDs:

• Program direction, including operation policies

• Allocation of funds

• Coordination and management of PSs

PS

PO

PS

PO

PD

Our PDs offer expert insight into key strategic fields of research. In addition to promoting collaboration between related fields, PDs monitor entire grant programs and make expansion and acceleration recommendations to AMED.

Our PSs possess a precise understanding of the aims and challenges related to their respective programs in order to effectively oversee operation.

The role of our POs is to assist PSs, taking responsibility for day-to-day program administration.

PD

PS

POPROJECTS WITHIN THE FIELD

PS

PO

Our Challenges

Like the rest of the world, Japan continually faces new and urgent public health challenges. The emergence of infectious diseases and prevalence of chronic conditions require constant attention, but perhaps the most significant challenge is the country’s aging population. Our government has defined its strategy to address this challenge, citing cutting-edge medical technology and care as vital to the creation of a society that enjoys longer, healthier lives. AMED is striving to meet this challenge head-on.

Life expectancy in Japan is among the longest in the world. However, the difference between life and healthy life expectancies stands at 8.84 years for males and 12.35 years for females. To shorten the gap, we focus on making discoveries that allow people to enjoy longer, healthier and more active lives.

Life and Healthy Life Expectancy (Japan)

19700

140

120

POPU

LATI

ON

(MIL

LIO

NS) 100

80

60

40

20

2060201520001985 2030 2045

NATIONAL INSTITUTE OF POPULATION AND SOCIAL SECURITY RESEARCH

HEALTHY LIFE EXPECTANCY

72.14 8.84YEARS

80.98

12.35YEARS74.79

87.14

50 90807060AGE

2016 MINISTRY OF HEALTH, LABOUR AND WELFARE DATA

FEMALE

MALE

LIFE EXPECTANCY DIFFERENCE

Our population is aging faster than that of any other nation. The percentage of those over 65 years old increased from 7.1% in 1970 to 26.7% in 2015, and it is predicted to reach 38.4% by 2065. As a result of this shift, the burden on our national healthcare system is greater than ever. That’s why finding effective solutions is one of our top priorities.

Population Structure (Japan)

2019

AGE

15—64

65+

0—14

05 06

BAS IC

R

ESE A RCH /AP P L IED S T U D Y: 50 %

PRE

CLI

NIC

AL/

CLI

NIC

AL

RE

SE

AR

CH

: 43%

OTHER: 7%

INITIAL BUDGET FOR FY2019*

¥127.1BN

Our Work in NumbersIn 2019, we are responsible for a budget of approximately ¥127 billion. Based on the nine key fields, we aim to ensure all spending offers maximum potential for beneficial outcomes.

In addition to these key fields, Cyclic Innovation for Clinical Empowerment (CiCLE) is currently active, but is carried forward from our supplementary budget from FY2016/17. The program focuses on the foundation of future-generation medical innovations, and the development of new drugs, devices, regenerative medicine, technologies and more. We are currently supporting 2,416 projects in 27 countries. Many of those projects are in the basic research stage, but we are also supporting a large number of pre-clinical and clinical studies.

Budget allocation and projects in development – all of AMED’s key figures at a glance.

*SOME BUDGET ALLOCATIONS OVERLAP; FIGURES IN JPY (USD: AT A RATE OF 110 YEN PER DOLLAR)2019/20 DATA

14.7BN (134M)

Regenerative Medicine

Translational & Clinical Research Core Centers

Emerging/Re-emerging Infectious Diseases

Psychiatric & Neurological Disorders Genomic

Medicine

FY2018 DATA

2,416Awarded Projects

We are working on 2,416 projects in total.

The project breakdown is shown here.

PROJECTS TO ELUCIDATE BIOMEDICAL & PATHOLOGICAL CONDITIONS

PROJECTS AIMED AT THE ADVANCEMENT OF MEDICAL

TECHNOLOGY & STANDARD OF CARE RESEARCH & DRUG

DISCOVERY INFRASTRUCTURE

OTHER PROJECTS

MEDICINE & DEVICE DEVELOPMENT PROJECTS

459

332 353

321951

23,500Researchers

Our global network of approximately 23,500 researchers is comprised of outstanding

individuals from leadingmedical institutions.

27Countries

We are currently involved in projects in 27 countries around the world.

12.4BN (113M)

Medical Devices

16.3BN (148M)Cancer

24.6BN (224M)

Other Programs

21.4BN (195M)

Drug Discovery

8.9BN

9.0BN

9.8BN

12.6BN (115M)

Rare/Intractable Diseases

5.7BN (52M)

(82M)

(89M)

(81M)

($1,155M)

07 08

Division of Regenerative Medicine Research

Division of Cancer Research

Division of Neurological, Psychiatric and Brain Research

Division of Rare/Intractable Disease Research

Division of Infectious Disease Research

Division of Medical Device Research

Division of Industrial-Academic Collaboration

Division of International Collaboration

Division of Biobank

Division of Emerging Research

Division of Clinical Research and Trials

Division of Strategic Planning & Evaluation

Division of Drug Research

Division of Regulatory Science

Department of Cyclic Innovation

DEPARTMENT

Research Promotion

Industrial-Academic Collaboration

International Affairs

Research Infrastructure

Clinical Research & Trials

Innovative Drug Discovery & Development

Cyclic Innovation

Grant ProgramsPromoting the development of innovative

drugs and strengthening support functions

for novel discovery.

21.4BN

Promoting research to realize genomic

medicine and create next-generation

precision medicine.

9.8BN

Developing novel medical devices driven by

clinical needs and supporting platforms for

developers to contribute to the promotion

of Japan’s medical device industry.

12.4BN

Promoting various activities from basic

research to clinical studies aimed at

accelerated practical application for cancer

diagnosis and treatment.

16.3BN

Promoting research and development

to improve the treatment of rare and

intractable diseases.

12.6BN

Strengthening core center functions to

achieve seamless implementation from

basic research to clinical application and

promoting use of innovative technology.

8.9BN

Promoting research and development for

dementia and other psychiatric disorders.

9.0BN

Supporting the research, development and

promotion of health and medical strategies

beyond the nine key fields.

24.6BN

Promoting the development of regenerative

medicine from basic research to clinical

studies and creation of evaluation standards.

14.7BN

Promoting research on emerging and

re-emerging infectious diseases for

effective control measures.

5.7BN

DRUG DISCOVERY & DEVELOPMENT

JAPAN GENOMIC MEDICINE PROGRAM

MEDICAL DEVICE DEVELOPMENT

JAPAN CANCER RESEARCH PROJECT

RARE/INTRACTABLE DISEASE

PROJECT OF JAPAN

TRANSLATIONAL& CLINICAL RESEARCH

CORE CENTERS

PSYCHIATRIC& NEUROLOGICAL

DISORDERS

OTHER PROGRAMS

JAPAN REGENERATIVE MEDICINE PROJECT

EMERGING/RE-EMERGING

INFECTIOUS DISEASE PROJECT OF JAPAN

PROJECT OFPROJECT FORPROJECT FOR

PROJECT FOR

We promote leading-edge medical innovation from discovery and development to clinical application. Focused on nine key fields, everything we do is guided by the Japanese government’s Plan for Promotion of Medical Research and Development.

Our projects are solicited through wide-ranging calls for proposals, which are aimed at outstanding individuals working in world-class institutions. Our role as custodians of public money means we consider each proposal thoroughly in order to

maximize the potential for beneficial outcomes.

Once projects are launched, we work to create the conditions necessary for discovery, establishing framework and putting together teams of distinguished researchers.

But our work does not stop there. We continue to support projects at every stage of their journey to ensure everything we do is underpinned by the highest quality and integrity.

FIGURES IN JPY, 2019/20 DATA

Promoting the establishment of infrastructure

to respond to medical needs, the creation of an

environment for open innovation and venture

development based on industry-academia-

government collaboration.

110.0BN*CYCLIC

INNOVATION FOR CLINICAL

EMPOWERMENT

* THE TOTAL SUPPLEMENTARY BUDGET CARRIED FORWARD FROM FY2016/201709 10

International CollaborationAt AMED, we understand that improving quality of life for people around the world is a global effort. That’s why we adopt an international approach, contributing Japanese expertise and actively engaging in research and development activities in collaboration with our counterparts around the world.

Bases of Cooperation Recognizing the importance of international collaboration and cooperation, we have established three overseas offices in Washington, D.C., London and Singapore. Their missions are to develop networks with overseas funding agencies, institutions, universities, scientists and researchers; promote overseas joint research and development programs; and collect and disseminate the latest information on medical science and technology.

Our Washington, D.C. office works to advance broad collaboration with our counterparts in the US and North and Latin America. There, we seek to create and maintain reliable relationships with the medical community in the region.

In London, our office is responsible for cultivating relationships and promoting our work among our counterparts in Europe, the Middle East and Africa. Our London office also organizes meetings, including a symposium on neuroscience in collaboration with the Medical Research Council (MRC).

At our Singapore office, located in Singapore Science Park I, we cooperate with countries throughout the Asia-Pacific region. In March 2019, our Singapore office operated the Asia Pacific Scientific Workshop at the National University of Singapore alongside NHMRC, NIAID/NIH and HRC. The aim of the workshop was to promote joint research, such as the e-ASIA Joint Research Program.

Our overseas offices allow us to exchange information on research policies and best practices, and build stronger connections with the countries in each office’s regions.

The first UK-Japan Neuroscience Symposium, co-organized by AMED and MRC. London, March 2018

AMED’s “GEM-Japan” Project Participates in GA4GH Driver Project

Following the recent advancements in large-scale genome analysis and technologies, responsible and secure sharing of genomic and health data is more vital than ever in order to accelerate research and

realize a society of healthy longevity. The Global Alliance for Genomics and Health (GA4GH) is the world’s leading alliance in this epoch-making collaboration, and AMED is proud to participate with our nationwide genomic health system: the “GEM-Japan” driver project.

GEM-Japan (GEnome Medicine Alliance Japan) aims to align our established projects with international standards, and promote the sharing of Japanese genomic and phenotypic information with the global community. Given the difference

Aligning the Young Stars of ScienceThe Interstellar Initiative recognizes the world’s most promising Early Career Investigators (ECIs) and connects them with peers. Introduced by AMED in partnership with the New York Academy of Sciences in 2018, it provides a platform to develop solutions to major medical research questions.

Following an annual international open call for participants, ECIs are selected and grouped into teams of three, including one Japanese member. Together, they devise research proposals for submission to international funding agencies under the guidance of mentors.

Each year, the theme of the initiative changes, and for FY2019, the focus is on “Healthy Longevity.” Successful ECIs will participate in two workshops in New York, US. The first will be held in September 2019, and the second in February 2020. Teams are expected to take a multi-disciplinary approach to tackling some of the world’s most critical medical challenges and unresolved research studies.

Through this project, AMED aims to accelerate the globalization of medical R&D, establish international research networks, stimulate joint research, and enhance the research capabilities of Japan. ECIs devise research proposals

under the guidance of mentors

Makoto Suematsu, President of AMED, introduces “GEM-Japan” at the GA4GH Connect Implementation Meeting in UK, April–May 2019

in genomic structure, the Japanese data will serve the analysis of genomic data from Western and/or African populations.

Furthermore, AMED has hosted GEM-Japan workshops to contribute to the creation of global frameworks and standards, as well as the localization of GA4GH tools in non-English speaking countries.

11 12

Other International Efforts

Japan’s Contribution to HFSP

1. UK-Japan Neuroscience SymposiumThe second UK-Japan Neuroscience Symposium was held in February 2019 in Chiba, Japan.

The three-day symposium brought together over 60 participants from Japan and UK universities, research institutes and funding agencies. Attendees took part in a range of presentations and roundtable sessions focusing on topics such as healthy aging, neurodegeneration, and the development of joint research. In addition, young researchers from both countries were tasked with creating posters, with the best being presented to fellow participants.

The symposium, based on the Memorandum of

Advocated by the Government of Japan at the Venice Summit in 1987, the Human Frontier Science Program (HFSP) provides flexible support for creative, ambitious and interdisciplinary research in the field of life sciences.

Since 1990, the program has been implemented by the International Human Frontier Science Program Organization (HFSPO), with its office in Strasbourg, France. Japan has been the largest contributor to HFSPO since its foundation, with financial contributions provided by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and the Ministry of Economy, Trade and Industry (METI) through AMED.

For almost 30 years, cross-border support has been provided to scientists from around the world, with a focus on collaborative research and grant projects. HFSPO has awarded approximately 1,000

Cooperation (MOC) signed by AMED and the MRC in February 2017, is an opportunity for new research partnerships and scientific collaborations to develop. It offers a new platform for joint research into neuroscience and mental health between Japan and the UK. 2.“Orphanet Japan” and “NAN-BYO Research”“IRUD Beyond” was established in 2017 to advance the research efforts of IRUD (page 24).

As part of this, a research group headed by Atsuhiko Kawamoto (Foundation for Biomedical Research and Innovation at Kobe) launched websites “Orphanet Japan” and “NAN-BYO Research” to

As part of our strategic international activities, we have established formal partnerships with some of the world’s leading funding agencies and government organizations.

To date, we have entered Memorandums of Cooperation with organizations in six countries: the National Institutes of Health (NIH), U.S.; the Agency for Science, Technology and Research (A*STAR), Singapore; the Medical Research Council (MRC), U.K.; the Ministry of Health, Lithuania;

the State Research Agency (AEI), Spain; and the National Health and Medical Research Council (NHMRC) in Australia.

Through our Strategic International Collaborative Research Program (SICORP), we are currently carrying out joint research in the fields of nanomedicine, with AEI in Spain, and aging, with A*STAR in Singapore.

We are also signatories of ten international consortiums: the International Rare Diseases Research Consortium (IRDiRC), the Global Research Collaboration for Infectious Disease Preparedness (GloPID-R), the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), the Global Alliance for Chronic Diseases (GACD), the Clinical

Data Interchange Standards Consortium (CDISC), the Global Alliance for Genomics

and Health (GA4GH), the International Human Epigenome Consortium (IHEC), the Matchmaker Exchange (MME), Translation Together (TT), and the International Cancer Research Partnership (ICRP).

Professor Anne Kelso, CEO of NHMRC, and Makoto Suematsu, President of AMED, signed a Memorandum of Cooperation in October 2018

The 2018 HFSP Awardees Meeting in Toronto

Partnerships for Progress

International Collaboration

spread knowledge in the field of rare and intractable diseases.

“Orphanet Japan” connects Japan with “Orphanet,” a global portal holding information on rare diseases and orphan drugs, while “NAN-BYO Research” introduces significant research achievements in Japan supported by AMED.

By actively participating in new data sharing opportunities and connecting with the international research community, we aim to promote the development of treatments for rare and intractable diseases.

We are currently involved in a number of other overseas collaborative research programs, two of which are highlighted below:

collaborative Research Grants involving 4,000 scientists worldwide, as well as 3,000 fellowships to young postdoctoral scientists. 28 Nobel Prize winners were supported by the HFSP Research Grant program prior to receiving the prestigious award.

Current HFSP Grant Awardees are invited to an annual meeting, which serves as a great opportunity to network with excellent scientists all over the world. 2019 marks the 30th anniversary of the program, and to commemorate this milestone, a ceremony will be held during this year’s Awardees Meeting in Japan in July.

Through such collaborations, we can collect information from around the world and contribute to joint international medical research and development. Our international partnerships also serve as an important platform for sharing Japan’s outstanding research results to the world.

Moving forward, we will continue to reinforce our international relationships, leveraging the strengths of each country through collaborative research, workshops and data sharing.

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Our Work Around the World

With a global network of researchers, institutions and organizations across five continents, we recognize the importance of international presence and collaboration.

AMED is currently implementing 8 international cooperative research projects that tackle 52 issues across 27 countries.

• e-ASIA JRP (e-ASIA Joint Research Program)

• ICREP-NTDs (International Collaborative Research Program for Tackling the Neglected Tropical Diseases Challenges in African Countries)

• J-GRID (Japan Initiative for Global Research Network on Infectious Diseases)

• SATREPS (Science and Technology Research Partnership for Sustainable Development)

• SICORP (Strategic International Collaborative Research Program)

• Global Health (Research Program on the Challenges of Global Health Issues)

• U.S.–Japan Cooperative Medical Sciences Program

• Research Program on Practical Application of Health Technology for Developing and Emerging Countries

In addition, our overseas offices serve as hubs to support our global network.

1

2

3

4

5

6

7

USA Infectious Diseases

Cancer Immunology

Nutrition

AMED WASHINGTON, D.C. OFFICE

BRAZILInfectious Diseases

EL SALVADORInfectious Diseases

1 7

7

7

4

4

4

2

DEMOCRATIC REPUBLIC OF THE CONGOInfectious Diseases2

UKAMED LONDON OFFICE

RUSSIAInfectious Diseases

INDIA Infectious Diseases

MONGOLIA Infectious Diseases

NEPAL Hypertension & Diabetes

PHILIPPINES Infectious Diseases Cancer Mental Health

INDONESIA Infectious Diseases Antimicrobial Resistance Medical Device Development

CAMBODIA Infectious Diseases Cancer

TANZANIA Hypertension & Diabetes

ZAMBIA Infectious Diseases

KENYA Infectious Diseases

GABONInfectious Diseases MYANMAR

Infectious Diseases Aging

CHINA Infectious Diseases

VIETNAM Infectious Diseases Antimicrobial Resistance Cancer Mental Health Medical Device Development

BURKINA FASOInfectious Diseases

NIGERIAInfectious Diseases

SPAINNanomedicine

EGYPT Infectious Diseases

AMED SINGAPORE OFFICE

SINGAPORE Aging

3

4

1 4

1

11

3

3

1

1

1

4

4

4

3

3

5

2

22

2 4

3

1

APR. 2019 DATA

JAPANAMED HEADQUARTERS 1 7

1

6GHANA Infectious Diseases32

REPUBLIC OF COTE D’IVOIRE

Infectious Diseases264

6

8

MALAYSIA Aging

Mental Health Medical Device Development

6

8

6

6

8

THAILANDInfectious Diseases

CancerMental Health

Medical Device Development

1

1

7

3

8

8

1

1 43

Global Successes Medical R&D has the potential to spare millions from suffering. We believe any outcome that makes life better is valuable – no matter how small. The following pages contain snapshots of the work we are currently involved in to ensure safer, more effective healthcare around the world.

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REGENERATIVE MEDICINE

The World’s First Allogeneic iPS-cell Transplant to Treat Parkinson’sCommitted to making Japan the global leader in the field of stem cell technology, AMED is supporting the iPS Cell Stock for Regenerative Medicine and the research and development of regenerative medicine based on stem cell technology.

Among the numerous treatment methods using induced pluripotent stem (iPS) cells currently under development, astonishing progress has been made in the area of Parkinson’s disease, a slowly progressing disorder in which dopaminergic neurons degenerate.

After more than 20 years of basic research to establish a therapeutic technique that is adaptive to humans, a research group headed by Dr. Jun Takahashi from CiRA validated the safety and efficacy of human iPS cell-derived dopaminergic neural progenitor cells in a primate model.

As part of an unprecedented clinical trial launched in October 2018, doctors from Kyoto University Hospital conducted the first-ever transplant of 2.5 million dopaminergic progenitor cells into the brain of a patient with Parkinson’s disease. The injected cells were generated from iPS cells prepared at CiRA’s iPS Cell Stock for Regenerative Medicine. The number of trial applicants attested to the great anticipation patients have for the treatment.

The transplanted cells are expected to mature into dopaminergic neurons that secrete dopamine, thereby easing some of the disease’s symptoms. The patient will be observed for two years to assess the engraftment of the transplanted iPS cells and to monitor for any adverse effects.

After thorough verification of the safety and efficacy of the treatment, doctors hope to have the treatment approved for the general public and covered by the national health insurance program.

Concept

Develop cell replacement therapy using iPS cells for Parkinson’s disease and contribute to diminishing motor dysfunction of patients through regenerative medicine. Establish this therapy as an alternative and more fundamental treatment for Parkinson’s disease in addition to existing medical and surgical treatments.

Progress

Commencement of a physician-initiated clinical trial using iPS cell-derived dopaminergic progenitor cells for treatment of Parkinson’s disease. A total of seven patients are scheduled to participate in the clinical trial, and each patient will be closely monitored for two years after the transplantation.

Collaborators

Kyoto University Center for iPS Cell Research and Application (CiRA); Kyoto University Hospital; Sumitomo Dainippon Pharma Co., Ltd.

GLOBAL SUCCESS 1

PROJECT FOR CANCER RESEARCH AND THERAPEUTIC EVOLUTION (P-CREATE)

Expanding on the Nobel Prize-winning research of Dr. Tasuku Honjo at Kyoto University on the role of PD-1 in cancer, AMED is supporting the research, development, and application of next-generation cancer therapies. The research project is focused on the discovery and application of biomarkers for the prevention and early detection of cancer, as well as the development of innovative cancer treatments.

Anti-PD-1 antibody therapy has revolutionized cancer treatment, with its antitumor effect attracting attention throughout the world. While good therapeutic outcomes for the PD-1 blockade therapy have been reported for various cancers, the efficacy of this treatment is not adequate for all patients.

One of the key areas of current research is the development of combination therapies that can enhance the antitumor effect of anti-PD-1 antibodies, thereby offering more effective treatment for patients unresponsive to the PD-1 blockade therapy.

Among the most significant findings to emerge from this research is the discovery of a key molecule that is important for mitochondrial activation in tumor-reactive T cells. By focusing on the energy metabolism of T cells, researchers

have also identified a number of low-molecular-weight compounds as potential concomitant agents that can enhance the antitumor effect of the anti-PD-1 antibody.

Moving forward, AMED aims to continue to strengthen the ties between basic and applied research that will help further revolutionize the therapeutic strategies for treating cancer.

Supporting Basic and Applied Research for the Development of Combination Therapies for Cancer

Concept

Develop new combination therapies to enhance the antitumor immune response by anti-PD-1 antibodies and overcome treatment unresponsiveness.

Progress

Several agents that potentiate PD-1 inhibitory antibody therapy have already been identified. A phase I clinical trial of combination therapy using a low-molecular-weight compound has been started in collaboration with Kyushu University. Several patents have been filed for combination therapy-related technologies, including factors and metabolites correlated with therapeutic efficacy.

Collaborators

Kyoto University; Kyoto University Hospital; Kyushu University

GLOBAL SUCCESS 2

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THE e-ASIA JOINT RESEARCH PROGRAM (e-ASIA JRP)

Realizing that improving the quality of life for people worldwide requires a global effort, AMED supports health research as part of the e-ASIA Joint Research Program (e-ASIA JRP). This program aims to solve common public health and medical problems in East Asia through multilateral international collaboration among a vibrant research community of institutions from several countries.

One example is the collaborative research on pulmonary diseases infected with influenza virus and tuberculosis conducted by Professor Kazuo Suzuki from Teikyo University in Japan and other members of the International Research Cooperation Team from Vietnam and The Philippines.

Their work has contributed to understanding the mechanisms of such infections that will help control occurrences in Southeast Asia. This includes strains EAI4_VNM and EAI5 in Vietnam, and the EAI2 Manilla strand that accounts for 90% of Mycobacterium tuberculosis in the Philippines.

A significant finding came from thesis work by a PhD student from Vietnam investigating the role of hypothiocyanous acid in severe pneumonia induced by influenza virus infection. Results showed that hypothiocyanous acid suppressed PolyI:C-induced antiviral responses by modulating IRF3 phosphorylation. The student, who was supported by MEXT, received a doctoral degree in influenza studies from Teikyo University Graduate School of Medicine in 2018.

In recognition of his numerous contributions to the Vietnam National Children’s Hospital and progress of medical care in the country, Prof. Suzuki was awarded the Medal for People’s Health by Vietnam’s Ministry of Health.

Looking ahead, AMED will continue to take an international approach toward research and development activities through multilateral collaboration in the field of health research.

Multilateral Collaboration Advances Our Understanding of Influenza and Tuberculosis Infection in Asia Concept

Investigate respiratory infection control through multilateral collaboration. Use the epidemiology information gained from collaborative research to develop international measures against respiratory diseases caused by influenza and tuberculosis infection.

Progress

A modeling simulation study revealed that the pathogenicity of the avian influenza virus H5N1 is altered by a single amino acid substitution. A clinical trial was launched in the Philippines to evaluate the effectiveness of Leucomycin A3 (Josamycin) in children with severe or very severe community-acquired pneumonia.

GLOBAL SUCCESS 4

Collaborators

Asia International Institute of Infectious Disease Control, Teikyo University and The Research Institute of Tuberculosis (Japan); Vietnam National Children’s Hospital (Vietnam); University of The Philippines College of Medicine (The Philippines)

THE JAPAN INITIATIVE FOR GLOBAL RESEARCH NETWORK ON INFECTIOUS DISEASES (J-GRID)

Forging Strong Research Ties to Combat Infectious Diseases Concept

Conduct clinical and epidemiological studies based on a cohort study to clarify the pathogenesis of viruses and epidemiology of respiratory viruses, primarily RSV. Utilize the results from these studies to develop new diagnostic methods, drugs, and vaccines.

Progress

There was a relatively large epidemic of RSV from September to December 2018. Epidemiological and virological analyses of data and samples obtained during the epidemic are expected to reveal the transmission dynamics of RSV within the community. Knowledge gained on RSV transmission will contribute to vaccination strategies.

Collaborators

Research Institute for Tropical Medicine (RITM, the Philippines)

In response to the worldwide threat posed by potential pandemic infectious diseases, AMED is supporting collaborative research centers through its J-GRID program. This program aims to establish relationships between research institutes in Japan and overseas research centers to promote epidemiological studies of infectious diseases and basic research into diagnostic methods and treatments.

With seven centers currently operating in Asia and two in Africa, Japanese and local researchers can leverage their knowledge and experience to tackle the current priority subjects of J-GRID, such as influenza, dengue fever, antimicrobial-resistant pathogens, and infectious diarrheal diseases.

One project is a cohort study conducted in the Philippines by Professor Hitoshi Oshitani from the Tohoku University Graduate School of Medicine in conjunction with colleagues from the Research Institute for Tropical Medicine (RITM) based in Metro Manila, local governments, and a hospital.

The study, made possible by a long-standing collaboration between Dr. Oshitani and researchers at RITM, has demonstrated an increased risk of subsequent respiratory infections in children after infection with specific viruses, including adenovirus, influenza virus, parainfluenza virus, and rhinovirus.

Another important discovery is an amino acid substitution at a specific antigen site in viruses detected in children who were reinfected with the respiratory syncytial virus (RSV), a major cause of severe respiratory infections in infants and young children. The change in antigenicity of the virus due to the amino acid substitution may be associated with the reinfection.

AMED hopes findings such as these from strong collaborative efforts will lead to

more effective interventions for disease prevention and control and also be utilized to develop evidence-based medicine.

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RESEARCH PROGRAM ON THE PRACTICAL APPLICATION OF HEALTH TECHNOLOGY FOR DEVELOPING AND EMERGING COUNTRIES

ADVANCED RESEARCH & DEVELOPMENT PROGRAMS FOR MEDICAL INNOVATION, INCUBATION-TYPE (LEAP)

As developing and emerging countries face public health issues different from those in Japan, AMED has established the Research Program on the Practical Application of Health Technology for Developing and Emerging Countries. The objectives of the program are to identify individual unmet medical needs at local clinical sites and work closely with companies to develop medical equipment that fulfills those needs.

In this program, AMED considers the design approach to be a key aspect to the product’s success, in addition to “immersion in the community”, which is integral for creating the health technologies to meet local needs.

The essence of the design approach is a thorough investigation of the local clinical environment to create a product development strategy. This includes a careful observation of the healthcare infrastructure to identify the unmet needs and then prioritization to maximize the results and impact.

Metran Co., Ltd. has been using this approach for the first time in Vietnam to develop a high-flow nasal cannula. They began by interviewing 22 medical personnel from five different healthcare centers, gathering information on the local needs over 10 days.

Through immersion workshops that offered firsthand experience, the company was able to observe the workflow and obtain a clearer perspective of the problems to overcome. This led to a design concept and ultimately the creation of a prototype to realize the concept.

Assessing the qualitative needs in such a way is the foundation of these overseas collaborative research efforts seeking to adapt Japanese technology for creating simple, efficiently engineered products that will improve the quality of life of people around the world.

Basic research generates scientific and medical innovation. One way AMED supports basic research is by promoting the Advanced Research & Development Programs for Medical Innovation (AMED-CREST, PRIME, and LEAP) to create and develop innovative seeds.

A breakthrough area attracting worldwide attention is the field of microbiome research. Professor Kenya Honda from Keio University School of Medicine has pioneered the development of essential technologies to identify host immune-modulating bacteria, using gnotobiotic animals and anaerobic culture.

Bacteria residing in the gut strongly influence the immune system and physiological function of the host. Dysbiosis, an imbalance in the body’s microbiome, is implicated in the pathogenesis of several immune disorders.

The research group headed by Dr. Honda sought to identify and isolate bacterial strains that activate CD8-positive T (CD8 T) cells, which are important for killing bacterial infected or cancer cells.

Preliminary experiments comparing specific-pathogen-free mice with germ-free (GF) mice, which do not contain any detectable microorganisms, led to speculation that intestinal bacteria may activate CD8 T cells and induce production of interferon gamma (IFNγ), an important immunomodulator exhibiting antibacterial and anticancer effects.

Inoculation of GF mice with fecal samples from healthy human donors demonstrated substantial induction of IFNγ-producing CD8 T cells, confirming the presence of intestinal bacteria that upregulate immune cell production. Additional screening led to the discovery of 11 rare bacterial strains that, when administered together, suppress pathogenic bacteria and enhance the response of anti-PD-1 antibody therapy in mice.

Further exploration of the gut microbiota is expected to lead to the development of novel approaches for preventing and treating infectious diseases and cancer in humans.

Solving Public Health Issues in Developing and Emerging Countries Using a Design Approach

Pursuing Innovative Medicine Using Gut Microbiota

Concept

Support efforts to solve public health issues in developing and emerging countries through collaboration between clinical practice and industry. Promote the development of medical technology that meets local needs using a design approach.

Progress

As the design approach, in the first year, researchers 1) grasp the unmet medical needs through immersion in the local clinical site and 2) formulate a product development plan and create a prototype. Business performance evaluations are also conducted for eventual launch of the product. In the second and third years, key activities include development and clinical evaluation of the product, development of strategies for commercialization, and application for regulatory approval.

Researchers

CMIC Holdings Co., Ltd.; Eiken Chemical Co., Ltd.; Japanese Organization for Medical Device Development, Inc.; Metran Co., Ltd.; Nihon Kohden Corporation

Concept

Identify specific bacterial strains among the gut microbiota or their antigenic compounds that contribute to modulating the host immune system.

Progress

Successfully demonstrated that administration of a cocktail of 11 intestinal bacterial strains to adult mice enhanced infection resistance and anticancer immunity. Results show that the 11 strains have great potential as broadly effective biotherapeutics for infectious diseases and cancer in humans.

Collaborators

Keio University School of Medicine; RIKEN Center for Integrative Medical Sciences; Waseda University, Faculty of Science and Engineering; Central Institute for Experimental Animals.

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The Program for an Integrated Database of Clinical and Genomic Information has established a nationwide alliance of universities, institutes, and hospitals committed to the promotion of genome-based medicine. Clinical information and genomic data collected from patients with rare diseases, cancer, infectious diseases, and dementia are securely stored locally and primarily used in research to investigate pathogenic variations, risk factors, and biomarkers.

Concept

Expand the comprehensive medical research consortium and maintain valuable clinical databases to improve the identification and diagnosis of rare and undiagnosed diseases. Collaborate with global efforts toward a coordinated diagnostic and research pipeline.

Aiming at further advancement of IRUD research outcomes

AMED established IRUD Beyond for the purpose of further advancing IRUD outcomes. It has three pillars: Beyond Diagnosis, discovering clinical treatment methods for IRUD targeted diseases; Beyond Genotyping, improving diagnostic methods; and Beyond Borders, enhancing global data sharing.

Principal of IRUD research group

(Head of IRUD Coordinating Center, Chairman of IRUD Executive Committee)Dr. Hidehiro Mizusawa, National Center of Neurology and Psychiatry

Patients with rare and intractable diseases face a long, arduous, and costly journey towards receiving a definitive diagnosis. IRUD, initiated by AMED, combines expertise and technology for a systematic approach to ending the diagnostic odyssey of patients with undiagnosed diseases.

The nationwide medical research consortium of the Initiative now has 37 IRUD Clinical Centers and about 400 cooperative hospitals, where complex cases can be reviewed by multi-disciplinary IRUD Diagnosis Committees comprising medical specialists and clinical geneticists. These are directed by the IRUD Executive Committee, with organizational support by the IRUD Coordinating Center.

Essential to this process are the five IRUD Analysis Centers that conduct next-generation sequencing. Findings are fed back to the committees to support ongoing discussions of cases.

The primary strength of the Initiative is the sharing of clinical results that have been collected and securely stored in a globally compatible patient-matching system, IRUD Exchange. Phenotypes are digitally encoded using the Human Phenotype Ontology, which enables data sharing with the global rare diseases community. The success of the Initiative since 2015 has led to definitive diagnoses for over a third of difficult-to-diagnose probands registered in Japan.

As IRUD continues to build its nationwide network, emphasis remains on the microattribution of all IRUD collaborators, from local primary healthcare professionals to patients, their family members, and anyone supporting patients.

Looking ahead, IRUD is committed to fulfilling AMED’s foundational role of international collaboration through global alliances, such as the International Rare Diseases Research Consortium, to accelerate progress towards helping undiagnosed patients with rare diseases.

PROGRAM FOR AN INTEGRATED DATABASE OF CLINICAL AND GENOMIC INFORMATION INITIATIVE ON RARE AND UNDIAGNOSED DISEASES (IRUD)

Summarized information on pathogenic or benign variants is integrated and open to the public in the Medical Genomics Japan Variant Database (MGeND). This compendium of knowledge on pathogenic variants will be indispensable clinically for the diagnosis of hereditary diseases, both rare and complex diseases, in the East Asian population. AMED believes that data sharing enables the reduction of the number of undiagnosed patients and the expansion of genome-based treatments, so as to maximize the benefits for patients.

The Japanese population and East Asian population, which occupy one-fifth of the world population, are genetically distinct from the European and African populations. MGeND can provide Japanese disease-associated variants to the global community as representative data of the Asian population to facilitate the understanding of human genomics as well as to improve health care systems, where the genomic data are more involved.

MGeND continues to expand since its release. Disease associations are categorized after the ClinVar’s classification: pathogenic, likely pathogenic, benign, likely benign, conflicting, risk factor, and uncertain significance. Data are updated every quarter of a year and publically available globally.

Data Sharing to Promote Practical Use of Clinical and Genomic Information

Integrating Knowledge and Sharing Data to End the Diagnostic Odyssey of Patients with Rare and Undiagnosed Diseases

Progress

The open access database of the Japanese variations associated with diseases was officially released in March 2018. There has been a steady increase in the total number of disease susceptibility variants included in the database and user access since the release.

Keio University; Kyoto University; Nagoya Medical Center; National Cancer Center Japan; National Center for Global Health and Medicine; National Institute of Infectious Diseases; Osaka City University; Shinshu University; The University of Tokyo (shown in alphabetical order).

Concept

Build a foundation to promote practical use of genomic medicine. Establish an integrated database of disease susceptibility variant information on Japanese patients available to the world.

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Researchers

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EXECUTIVE DIRECTOR

Our structure is our strength. It provides us with the flexibility to be decisive and forward thinking.

The different roles of our departments are aligned to create an interdisciplinary approach that inspires innovation.

DEPARTMENT

OFFICE OF AUDIT

Our OfficesAMED Structure

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DEPARTMENT OF INNOVATIVE DRUG DISCOVERY AND DEVELOPMENT (WEST JAPAN OFFICE)

PRESIDENT

AUDITOR

AUDITOR

COUNCIL OF RESEARCH AND MANAGEMENT

ADVISORY BOARD

PLANNING & MANAGEMENT

GENERAL AFFAIRS

FINANCIAL AFFAIRS

RESEARCH INTEGRITY & LEGAL AFFAIRS

INTELLECTUAL PROPERTY

RESEARCH PROMOTION

INDUSTRIAL-ACADEMIC COLLABORATION

INTERNATIONAL AFFAIRS

RESEARCH INFRASTRUCTURE

CLINICAL RESEARCH & TRIALS

INNOVATIVE DRUG DISCOVERY & DEVELOPMENT

CYCLIC INNOVATION

Division of Regenerative Medicine Research

Division of Cancer Research

Division of Neurological, Psychiatric & Brain Research

Division of Rare/Intractable Disease Research

Division of Infectious Disease Research

Division of Medical Device Research

Division of Industrial-Academic Collaboration

Division of Biobank

Division of Emerging Research

Division of Clinical Research & Trials

ADMINISTRATIONSECTION

PROJECT SUPPORTSECTION

PROJECT MANAGEMENTSECTION

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SINGAPORE OFFICE

The location of our headquarters is marked on the cover

Division of Strategic Planning & Evaluation

Division of Drug Research

Division of Regulatory Science

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