Japan Agency for Medical Research and Development (AMED)

Missions and Challenges

Makoto Suematsu, MD, PhDPresident

Japan Agency for Medical Research and Development

JSGT2015 and APGTC2015 in Osaka July 24, 2015

3 “MUST NOT” rules in AMED organization

A success of AMED (Japan Agency for Medical Research and Development) highly depends on alliance and cooperativity of three ministries (METI, MEXT, MHLW)

To this end, we need to challenge for an art of probability……..

AMED (1.4 billion US$/FY2015)

METI MEXT MHLW

Not only budgets but also officers and scientists with new mindsets

Our goal is to fast-track medical R&D that directly benefits people not only by extending lifespans but also by improving quality of life:supporting “life” as biological existance, diary living, and lifespans

Office of Audit

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Department of General Affairs

Department of Industrial-Academic Collaboration

Department of Research Promotion

Department of Research InfrastructureDepartment of Clinical Research and Trials

Department of International Affairs

Department of Intellectual Property

Department of Research Integrity and Legal Affairs

Department of Innovative Drug Discovery and Development

Department of Financial Affairs

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Department of Planning and Management

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Permanent Staff Fixed-term Staff

102 Approx. 200

Organization of AMED

Drug Research

Regenerative Medicine Research

Cancer Research

Infectious Disease

Research

Neurological. Psychiatric and Brain Research

Rare/In-tractable Disease

Research

Emerging Research

Support for accommodating R&D platforms such as BioBank, etc.

Promotion of strategic international researches

Support through the Drug Discovery Support Network for realizing academia drug discovery

Support for practical application such as industrial-academic collaboration

Longitude/cross-sectional collaboration between “Department of Research PromotionMatrix structure for accelerating Medical R & D

Support for high-quality clinical studies/clinical trials

7 Research Projects

3

Undiagnosed Disease Program in NIHdiagnose (and treat) those undiagnosed ( from 2008, Dr William Gahl, NIH)

Undiagnosed Disease Patients

Home doctors Regional Core Hospitals

Collection of data and

examination

Genome analysis center

Medical Consultation

Local Specialists of Clinical Genetics

The Japan’s National Liaison Council for Clinical Sections of Medical Genetics etc.

G and M data

Genetic counselling

Diagnose known diseases

Assessment by specialist of clinical

genetics

Return of the Research Findings to Patients Individually

Known ones？

Analyses by physicians with

different specialties

Data banking

Judge treatable or not ?

Phenotyping

NGS (ISO, CLIA etc)

metabolomics

Strong team of physician scientists

4

Mutation of riboflabin receptor causes “ALS-like” severe phenotypes in a newborn baby.

Johnson et al Brain 2012:135；2875-2882

AMED will start✔ Joining in IRDiRC in this autumn✔ Organizing IRUD (Initiative for Rare and undiagnosed diseases)

under collaboration with NIH-UDP Program

Dr. William Gahl, MD, PhDFounder of undiagnosed Patients Program, NIH

“Not sequencers but real physicians” “ Phenotype is everything”

N Engl J Med. 2015 Jun 4;372(23):2235-42

In genome medicine, “likely pathogenic” variant now may turn out “likely benign” 5 years later;Necessity for real-time data sharing of clinical genetics through DB

IRUD診断連携・IRUD診断委員会は地域の拠点病院

等に配置し、全国配備を目指す

紹介受診

フォローアップ

エントリーシート(臨床・検査データ)

受診

IRUD診断委員会・幅広い診療科の医師で構成・臨床遺伝専門医を中心として臨床カンファレンスを開催・地域の臨床医と積極的に連携し地域をあげて取り組む

IRUD解析コンソーシアム

IRUD解析センター

・依頼された検体についてエクソーム解析等の遺伝学的検査を行う・遺伝学的検査以外の検査や遺伝子変異の機能解析も検討する

解析結果

検査依頼

診断困難な患者さん

AMED データセンター

・登録システムの構築・運営・データベースの構築・運営・国際ネットワークとの連携

IRUDデータネットワーク

データ

診断説明カウンセリング

IRUDに参加する拠点病院（総合病院）地域での

密接な連携

AMED has launched Initiative for Rare and Undiagnosed Diseases

(IRUD)

症例検討依頼 検討結果

フィードバック

IRUD臨床専門分科会

・疾患エキスパートによる専門分科会・IRUD診断委員会による依頼を受け、専門的な症例検討を追加する・必要に応じてIRUDに参加する拠点病院で直接診療

IRUDに参加する拠点病院

IRUD診断委員会

・幅広い診療科の医師で構成・臨床遺伝専門医を中心として臨床カンファレンスを開催・地域の臨床医と積極的に連携し、地域をあげて取り組む

IRUDに参加する

拠点病院が全国に設置されるよう体制整備を支援していく

IRUD constitutes a network consisting of multiple hospitals to save patients with RUD with equal opportunities all over Japan

Japan has joined IRDiRCin July 30, 2015

✔ Machine-readable consent

✔ microattribution

✔ data sharing for patients

AMED has participated in IRDiRC to share IRUD data for saving patients over the world

Advocacy activities by patients and their supporters;Patients constitutes a stakesholder that participates in designing clinical researches

Increase and influence government and private

funding for research

Promote running “smart” clinical trials

Heighten public awareness and visibility

Increase clinical trial enrollment rate

Identify the best practices and disseminate them across the

country

2015 2020

Permission by Julie Fleshman, President and CEO, PanCan

Discovery Innovation Screening Consortium: DISC

Purpose: Enrich “All Japan” screening library by integrating unique compounds ofpharmaceutical companies for use in HTS by the Drug Discovery Support Network

Univ. of TokyoLow MW compounds

AIST（N2PC）Natural products

NIBIOHNmAb-Phage/aptamer

AMED/iD3Low MW compoundspharma-companies

・Highly patentable, unique structures

Pharma A

Compound storage, assay plate preparation, HTS implementation and cherry picking to be outsourced to industry

・Tool compound discovery

・Lead discovery

・HTS by RIKEN

Impact of DISCWhole: create the first non-competitivecollaborative space in Japan and improve overallpharma R&D productivity

Academics: increase the chance to find qualitylead and tool compounds for their own newlydiscovered targets

Industry：maximize potential value of their own

compounds through increased chance to bescreened out against new targets discovered byuniversities, etc.

HTS

YCo. LtdPharma B

Pharma CPharma DPharma E

“All Japan” Screening Library

Storage assay-plate

preparation

XCo. Ltd

Already established:AIST, NIBIOHN, Univ.Tokyo

Pharma･･

Public-Private Partnership to take advantage ofunique compounds & HTS technology of pharma-industry for more effective translational research● iD3 to select targets & cover HTS cost● Pharma to provide access to premiumcompounds and HTS technology/equipment

DISC

CONFIDENTIAL

Input scaffold

information

Copyright © 2015 All Rights Reserved.

Liver tox risk

Side effect

Metabolizing

enzyme

Plasma stability

：0.002

：ILD

：CYP2C8

：Stable

structure information

X Tox DB

Physico-chem DB

ADME DB

DB integration

e.g. DISCHit candidates

True hit identification

eye ball

structure design

synthesis

Lead compound generation

Example ofthe system architecture

Schematic flow for the use of the system

Schematic diagram of the system

Output ADEM-T

information

Input scaffold

information

Output ADEM-T

information

To construct a system that can predict toxicological risk etc. with a certain significance levelby integrating various databases developed to date in our country, while identification of truehit compounds and generation of lead compounds have been done by eye ball of medicinalchemists with experience and expertise.

Constructing the system within 3 years, followed by the 2-year validation period

IT system for Supporting Development of Drug Discovery

Structure

optimization

unit

Platform for Drug Discovery, Informatics

and Structural life science

Toxicity・ADME information

AMED Mission1 Global Cooperation for Controlling Diseases:

①Infectious diseases②Regenerative medicine③Neuropsychiatric diseases④Rare diseases (and undiagnosed diseases)

and R/D for orphan drugs

2 Empowerment of Medical R&D in Japan① Opening resources of drug libraries② Accelerating nation-wide registry for optimizing cancer Tx③ Establishing infrastructure of clinical genetics (CLIA lab, etc)④ Fostering young physician scientists for medical R/D⑤ Utilization of private-public partnership to stimulate medical R/D

3 Renew selection processes and improve flexibility of budget systems4 Clinical database

(under supervision by Cabinet Secretariat, Office of Healthcare Policy)14