EU-Japan Centre for Industrial Cooperation

Opportunities for Cooperation between EU and Japan on
Biotechnology in Healthcare: Japan Bioventures LandscapeTokyo, April 2018
Esther RODERGAS

1

Disclaimer
The information contained in this publication reflects the views of the author and not necessarily theviews of the EU-Japan Centre for Industrial Cooperation, the European Commission or Japanauthorities. The author believes that this paper is reliable and reasonably clear. While utmost care
was taken to check and translate all information used in this study, the author and the EU-Japan
Centre may not be held responsible for any errors that might appear. This report does not constitutelegal advice in terms of business development cases.
The author can be contacted at esther.rodergas@gmail.com

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Executive Summary
Japan is one of the major countries that European biotech companies target in their expansion whenit comes to internationalisation. This report intends to be a useful source of information for European
SMEs and clusters considering potential cooperation with Japan.

In the healthcare sector, and more specifically in the therapeutics development field, partnerships
between European and Japanese pharmaceutical companies well established in their respective local
markets has typically involved License agreements on co-development and commercialisation rights.
The Japanese inlicensor would typically get the rights on a product of European origin to pursue its
clinical development in Japan, obtain the local regulatory approval, and commercialise it in thedomestic Japanese market. The reverse situation was possible as well, when products developed inJapanese companies pipelines were licensed-out to European based companies.

In an era of open innovation, partnership models are evolving, and can go well beyond pharma
licensing deals on co-development and product commercialisation rights. Moreover, European
biotech SMEs often present alternatives to the traditional therapeutic product development, andbusiness models are frequently based on discovery platforms and services to facilitate research anddrug development.

This report is therefore focussing on public research institutions and academic bioventures in Japan,
which may hold great potential for collaboration with European SMEs.

Biotechnology policies in Japan are presented in the first section of the report, exploring theRegulatory mechanisms for approval of regenerative medicines which Japan pioneered (sections
2&·3). A brief presentation of Japan science and technology indicators, and major cooperation
programs in health with the European Union is given in sections 4&5. The chronology of theevaluation of Academia-Industry relations in Japan, leading to the current situation of academic
bioventures is presented in sections 6 & 7.

Section 8 includes an overview of the Japanese biotech academic landscape. A comprehensive
description of all the laboratories doing biotech research in Japan was beyond the scope of this report.
Major universities and flagship research centres are presented, explaining how relations withindustry are organised for each centre. A selection of innovative academic bioventures is provided,
linked to the research laboratory which was at the origin of the technology offered by thesecompanies.

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The global health innovative technology fund is presented in section 9, as an interesting model of
tripartite collaboration with Japan, potentially interesting to EU biotech companies.

Section 10 describes the most active Japanese clusters and innovation hubs with interest on
international collaboration biotechnology and healthcare.

The report concludes with some practical recommendations for EU biotech companies considering
entering the Japanese market.

4

List of abbreviations

AMED

Agency for Medical Research and Development

ALS

Amyotrophic Lateral Sclerosis

CiRA

Center for induced pluripotent stem cell Research and Application

CDMO

Contract development and manufacturing organization

CRO

Contract Research Organization

EMA

European Medicines Agency

EU

European Union

ES

Embryonic stem cell

FDA

Food and Drug Administration (US)GDP

Gross Domestic Product

GHIT

Global Health Innovative Technology Fund

GMP

Good manufacturing Practices

HFSP

Human Frontier Science Programme

HGF

Hepatocyte Growth Factor

iPSC

Induced Pluripotent Stem CellIFReC

The Immunology Frontier Research Center

IMSUT

Institute of Medical Science University of Tokyo

ICGCInternational Cancer Genome Consortium

IHEC

International Human Epigenome Consortium

IHMC

International Human Microbiome Consortium

IMPC

International Mouse Phenotyping Consortium

IoT

Internet of Things

JABEX

Japan Association of Bioindustry Executives

JBA

Japan biotechnology Association

JPY

Japanese Yen

LiCLifescience Industry Center in Kanagawa

LINK-JLife science Innovation Network Japan

MHLW

Ministry of Health Labour and Welfare

MAB

Monoclonal Antibody

METI

Ministry of Energy Trade and Industry

MEXT

Ministry of Education, Culture, Sports, Science and Technology

MOTHERS

Market of High Growth and Emerging Stocks (Tokyo Stock Exchange)

MoU

Memorandum of Understanding

5

M&A

Mergers and Acquisitions

NEDO

New Energy and Industrial Technology Development Organization

NGS

Next Generation Sequencing

NISTEP

National Institute of Science and Technology Policy

OECD

Organisation for Economic Co-operation and Development

PMDA

Pharmaceuticals and Medical Devices Agency

PMI

Preventive Medicine and Diagnosis Innovation Program

QbIC

Riken Quantitative Biology Center

RCAST

Research Center for Advanced Science and Technology

RMP

Regenerative Medicine Product

RPE

Retinal Pigment Epithelium

SMEs

Small and Medium Size Enterprises

6Table of contents

Disclaimer .............................................................................................................................................2
Executive Summary ..............................................................................................................................3
List of abbreviations .............................................................................................................................5
Table of contents ...................................................................................................................................7
List of Bioventures/companies mentioned in the report: ......................................................................9
List of Figures ..................................................................................................................................... 11
List of Tables.......................................................................................................................................12
1.

Introduction ...............................................................................................................................13

2.

Japan Biotechnology Policies ...................................................................................................15

3.

Regulatory policies for the promotion of Regenerative Medicine ........................................17

4.

Japan Science and Technology Indicators ..............................................................................21

5.

European Union-Japan Cooperation on Health.....................................................................24

6.

Industry- Academia Collaborations in Japan.........................................................................26

7.

Entrepreneurship and policies supporting Bioventures in Japan ........................................30

8.

Japan Academic Landscape- An Overview.............................................................................34
Internationalization of Japan Universities: Japan Top Global Universities Project ................................................. 34
World Premier International Research Center Initiative (WPI) ............................................................................... 35
Industry-Academia track record of collaborations................................................................................................... 37
University start-up creation: Accumulated number of academic ventures ............................................................... 37
The University of Tokyo .......................................................................................................................................... 38
The Institute of Medical Sciences of the University of Tokyo (IMSUT) ................................................................. 38
The Translational Research Initiative by the University of Tokyo........................................................................... 39
The Research Centre for Advanced Science and Technology (RCAST) ................................................................. 41
The University of Tokyo- Organisation of the Collaborations with Industry .......................................................... 42
Support to venture companies at the University of Tokyo ....................................................................................... 427

Kyoto University ..................................................................................................................................................... 48
Center for iPS Cell Research and Application (CiRA) ............................................................................................ 48
Institute for Integrated Cell Material Sciences (ICeMS) ......................................................................................... 50
Kyoto University: Industry-Academia Collaborations Organisation ....................................................................... 50
Osaka University ..................................................................................................................................................... 58
The Immunology Frontier Research Center (IFReC) .............................................................................................. 58
Osaka University: Industry-Academia Collaborations Organisation ....................................................................... 59
Examples of Academic bioventures from other Universities (Hiroshima, Nagoya, Hokkaido, Kyushu, Kurume,
Keio, Saitama) ......................................................................................................................................................... 63
RIKEN Research Institutes...................................................................................................................................... 66

9.

Global Health R&D fund (GHIT): An alternative public-private partnership model .......78

10.

Industrial Clusters and Innovation Hubs...........................................................................79

Life Science Innovation Network Japan (LINK-J)

TOKYO .............................................................................. 80

Life Innovation Centre (LiC) in Kawasaki, Kanagawa Prefecture .......................................................................... 82
The Shonan Health Innovation Park, Kanagawa ..................................................................................................... 84
Kobe Foundation for Biomedical Research and Innovation .................................................................................... 85
Osaka Bio ................................................................................................................................................................ 87

11.

Academic Societies and Associations ..................................................................................87

12.

Tradefairs and Organisations ..............................................................................................90

13.

Recommendations and Conclusion .....................................................................................90

Annexes ..............................................................................................................................................92
Annex 1: Japanese bioventures exhibiting at Japan Healthcare Venture Summit 2017 ........................................... 92
Annex 2 List of National Universities ..................................................................................................................... 94

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List of Bioventures/companies mentioned in the report:

Originating from
Company name

University/ Institution

Ambicion

RIKEN

AnGes

Osaka

Brightpath Biotherapeutics Co Ltd

Kurume, Fukuoka

LiC & Fukuoka Bio incubation

Cellink

Kyoto

KU innovation hub, EU

Chiome bioscience

RIKEN

LiC Kanagawa

Chordia therapeutics

Kyoto

Shonan Park, Kanagawa

Chromocenter Inc.

Osaka

Cyfuse biomedical KK

KyushuTokyo U entrepreneurs plaza

DNAform

RIKEN

Venture plaza Yokohama

EdigeneTokyo

Cambridge,MA, USA

Epigeneron Inc.

Osaka

Epsilon Molecular Engineering

Saitama

FunpepOsaka

GlyTech Inc.

Tokyo

HanaVax Inc

Tokyo

Healios

RIKEN

Human Metabolome Technologies

KeioiHeart Japan

Kyoto, CiRA

Jisak bioengineerng

Tokyo

JTEC corpo

Osaka

K Pharma

Cluster/ innovation hub/area

Saitama

Tokyo

Tokyo, EU/US

Shonan Park, Kanagawa

Kinopharm

Kyoto

Kyoto innovation hub

Kotai Biotechnologies Inc.

Osaka iFReC

Kyoto drug discovery KDDD

Kyoto

Matrixiome Inc.

Osaka iFREC

MedinetTokyo IMSUTTokyo Yokohama Osaka

MegaKaryon Corporation

Kyoto, Tokyo

Kyoto

MetcelaKeio

LiC Kanagawa

MolcureTokyo

Myoridge

Kyoto

KU pharma research institute

NB Health Laboratory Co. Ltd

Sapporo University

Hokkaido

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Noile Immune

Yamaguchi University

Shonan Park, Kanagawa

Nuprotein

NagoyaNagoya University Incubation

Organ technologies

RIKEN

Peptidream

Tokyo RCAST

LiC Kawasaki

Peptistar

Tokyo RCAST

LiC Kawasaki

PharmaBio

Tokyo

Tokyo

RegCell

Kyoto, Osaka

ReproCell

Kyoto iCeMS

LiC Kanagawa /EU/USA

Rhelixa

Tokyo RCASTTokyo

Rikenbio

RIKEN

SCAD

Kyoto ICeMS

SCI

Kyoto

Scohia Pharma Inc.

TakedaShonan park Kanagawa

TagCyx biotechnologies

RIKEN

Tokyo Komaba open lab

Thyas

Kyoto

Two cells

Hiroshima

Hiroshima

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List of Figures

2.1

Japan government strategies fostering the Smart-cell Industry

2.2

Image from the roadmap of the comprehensive strategy on STI

3.1

Timelines for conditional approval vs normal approval

4.1

R&D expenditure in selected countries.

4.2

Changes in government budget for Science and Technology as percentage of GDP

4.3

Number of top 10% cited papers as a proportion of total papers by country

4.4

Evolution in Japan R&D spending and share of highly cited papers

6.1

Industry Academia Collaboration Promotion Policy in Japan

6.2

Guidelines for enhancing Academy-Industry-Government Collaboration activities

7.1:

Trend in the number of university based start-ups in Japan

7.2

Number of university based start-ups in Japan, per sector

7.3

Worldwide Venture Capital investment distribution by industrial sector

8.1

World Premier International Research Center Initiative

8.2

University Corporate relations database of proposals- University of Tokyo

8.3

Collaborations from iPS Academia Japan Inc.

8.4

Kyoto University private sector collaborative projects

8.5

Collaborative research schemes at Kyoto University

8.6

KUMBL organization at Kyoto University

8.7

Fund scheme by Kyoto University Innovation Capital Co. Ltd. (KU-iCap)

8.8

Osaka University Office for Industry-University Co-Creation website

8.9

Osaka University research seeds website

8.10

Illustration on different bioressources provided by the BRC Divisions

8.11

Left exterior of RIKEN CDB. Right, photography of Kobe

8.12

Left: iPS cells and RPE cell sheets; Right Prof. Masayo Takahashi

8.13

RIKEN Baton Zone program

8.14

RIKEN Program for Drug Discovery and Medical Technology Platforms DMP

10.1

LINK-J Tokyo situation

10.2

Tella pharma Inc manufacturing facility at LiC

10.3

Kobe BRAVE Program11

List of Tables
1.1

OECD Biotechnology list based statistic definitions

3.1

Regenerative medicines approved in Japan under the revised legislation

3.2

Sakigake comparison with other regulatory designations for expedited approval

3.3

Sakigake designations for regenerative medicine products 2016-2017

4.1

Japan Nobel Prize laureates in life sciences

8.1

List of Japan Top Global Universities (as of January 2018)

8.2

WPI research centers related to healthcare biotechnology

8.3

Ranking of universities receiving highest income from collaborations with Industry

8.4

Japanese universities by number of ventures (all fields confounded) in Fiscal year 2017.

8.5

Examples of companies having originated as the University of Tokyo Bioventures

8.6

EU licensors of CiRA technology identified from iPS Academia Japan website

8.7

Examples of Bioventures supported by Kyoto University (KU-iCap)

8.8

Other bioventures companies based on technology originating from Kyoto University

8.9

Examples of Bioventures originated at Osaka University

8.10

Examples of Bioventures spawning from other Japanese Universities

8.11

RIKEN Bioventures

10.1

Presented Industrial Clusters and Innovation Hubs

10.2

Japanese life science organisations with office at LINK-J premises

11.1

Other Japanese Academic Societies of interest to biotech companies in Europe

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1.

Introduction

This report intends to provide an overview of the current biotechnology landscape in Japan,
focussing on key academic institutions and bioventure companies which are developing applicationsof biotechnology to healthcare.

The objective of the report is to be a useful source of information for European SMEs and Clusters,
wishing to explore collaborative research and potential business opportunities in Japan. With thisaim, a selection of academic institutions is presented, highlighting those centres with worldwide
recognition for their research, broad support for internationalisation, and a track record of openness
for Industry-Academia collaborations.

Research for the preparation of this report was undertaken during the last quarter of 2017 and firstquarter of 2018. During that period, the monitoring of Japanese biotechnology specialised press,
tradefairs, seminars, and related events, revealed the bioventures ecosystem as a very dynamic groupof innovative companies in the Japanese biotech landscape today, increasingly attracting interest andsupport both from public and private sectors.

This report has focussed on Japanese bioventures, created to commercialise results of research anddevelopment from Japanese forefront academic research institutions. Information on governmental,
university-related, and private initiatives supporting these bioventures is also presented, as it may beof interest to European biotechs wishing to interact with their Japanese counterparts.
For a European company considering business development in Japan, it may be relatively easy toaccess information on main players in the Japanese market, such as big pharmaceutical corporations.
In contrast, information on emerging companies and start-ups in Japan is scarce, and less broadly
available. Small biotech research firms correspond to a reservoir of industrial competitiveness,scientific and technologic innovation worldwide, and Japan is no exception to this.

European biotech start-ups interested in the Japanese market, dealing with advanced therapy
medicinal products, often have questions concerning the regenerative medicine regulatory
provisions that Japan has been promoting. A specific section of this report is devoted to theseregulatory changes and mechanisms, providing detailed examples of products authorised forcommercialisation in Japan under the revised legislation. The author hopes to have contributed toshed some clarity on this topic.

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The terms “venture” and “bioventure” are frequently used in English language in Japan. They referto biotech start-up companies, often based on technology developed at universities, and usuallyfunded through venture capital and/or public sector funding.
The terms “biotechnology” and “biotech” are used interchangeably throughout the report, the latteroften referring as well to companies operating in the field.

Biotechnology, as commonly understood in the public science & technology policy and in economic
analysis, is defined as the application of science and technology to living organisms, as well as parts,
products and models thereof, to alter living or non-living materials for the production of knowledge,
goods and services. For the identification of target academic research institutions and companies ofinterest in this report, the applications listed under “Human Health”, and biotechnology list based
statistic definitions1 published by OECD in January 2018, have been considered.

Nanotechnology has not been specifically covered in this report. For an overview on the Japanesenanotechnology landscape, see the report2 “Nanotech Cluster and Industry Landscape in Japan” byAndrej Zagar, published in 2014 by the EU-Japan Centre for Industrial Cooperation.

Table 1.1: OECD Biotechnology list based statistic definitions

1

Friedrichs, S. and B. van Beuzekom (2018), “Revised proposal for the revision of the statistical definitions ofbiotechnology and nanotechnology”, OECD Science, Technology and Industry Working Papers, 2018/01, OECD
2
Nanotech Cluster and Industry Landscape in Japan

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2.

Japan Biotechnology Policies

For the government of Japan, the biotech-based economy/industry is an integral part of Prime
Minister Abe Administration growth strategy, as captured in the “Basic Policy on Economic andFiscal Management and Reform 2015”3. The Ministry of Energy Trade and Industry (METI) aims tofoster the biotech-based economy, projected to grow as large as six times by the year 2030, throughthe development and commercialization of the innovative technologies, products and services,notably including regenerative medicine.
In 2016, METI issued the document “New trends in the field of biotechnology and its impact onsociety and economy: Creating Smart Cell Industry” 4 where it was recognised that cell
technology, with its innovative potential, will bring about transformative changes in industrial
structure and operation of major industrial fields and provide the basis to address global challenges.
Figure 2.1: Japan government strategies fostering the Smart-cell Industry

Source: METI
3
4

New trends in the field of biotechnology and its impact on society and economy: Creating Smart Cell Industry
http://www.meti.go.jp/english/press/2016/pdf/0714_01a.pdf

15

In Japan, the Science and Technology Policy is administered according to the directives andprinciples contained in the Science and Technology Basic Plan, which is approved every five years.
Currently, the 5th Science and Technology Basic Plan5, endorsed in by Cabinet Decision in January
2016, is running for the period 2016-2021. The objective of the plan is to achieve a higher standardof science and technology, to contribute to the development of the economy and society of Japan.
It includes a series of measures to promote translational R&D, particularly in the field of
regenerative medicine, where the market is expected to expand from 9 billion yen (€67.5 million) in
2012 to 1 trillion yen (€7.5 billion) in 2030.
Since 2014, the roadmaps of the comprehensive strategy on Science, Technology and Innovation,
include promotion measures towards the social implementation of regenerative medicine:-Promotion of contiguous basic research, clinical research and practical applications of somatic
stem cells, embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells)-

Establishment of infrastructure for regenerative medicine industry-

Preparation of development guidelines

Figure 2.2: Image from the roadmap of the comprehensive strategy on STI

SOURCE: GoJ

5

http://www8.cao.go.jp/cstp/english/doc/chapter2_roadmap_provisional.pdf

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3.

Regulatory policies for the promotion of Regenerative Medicine

Several regulatory-led initiatives were designed in Japan to promote the research and developmentof regenerative medicine products6. In November 2013, two legislative acts were promulgated by theJapanese Diet (Parliament), and enacted in November 2014: The PMD Act and the Safety RM Act.

-

PMD. Act: The Pharmaceutical Affairs Law was revised and renamed Pharmaceuticals, Medical
Devices and Other Therapeutic Products (PMD Act), to include a new independent classification
for regenerative medical products (RMPs). It established a conditional approval scheme forcommercialization of RMPs based on confirmation of probable benefit and safety, whereby
RMPs would receive a temporary approval, initially valid for up to 7 years.

Figure 3.1: Timelines for conditional approval vs normal approval

SOURCE: PMDA

- The Act on the Safety of Regenerative Medicine (RM Act) created a framework to provide
regenerative therapies in early-stage, small scale clinical research, under physician discretion.
These provisions are similar to the “Hospital Exemptions” existing in many EU member states.
The act also enabled the outsourcing of cell processing to contract GMP compliant
manufacturing organizations, holding a license as “Cell Processing Center”.

RMPs were defined in legislation as processed human/animal cells that are intended to be used either
1) for the reconstruction, repair or formation of structures or functions of the human body;or for the treatment or prevention of human diseases.
2) for gene therapy.

6

Azuma K., Yamanaka S. Recent policies that support clinical application of iPS cell based regenerative therapies.
JSRM, 201617

Table 3.1: Regenerative medicines approved in Japan under the revised legislation

TEMCELL® HS Inj., by JCR Pharmaceuticals Co. Ltd. are human allogeneic bone marrowderived mesenchymal stem cells (MSCs) for the treatment of acute graft versus host disease,arising from hematopoietic stem cell transplant.
It was approved under regular authorization in September 2015, and launched in February 2016.
Temcell was developed in Japan with a license on the technology from Australian company
Mesoblast Ltd., who had acquired the product (Prochymal) from Osiris Therapeutics Inc. (US).
Prochymal was approved in Canada and New Zealand in 2013.
The clinical package submitted for its marketing authorization application in Japan, included
around 40 Japanese patients treated with Temcell. Overseas experience with Prochymal, as
supportive data, included 173 patients treated with the product. Data on all cases treated with the
product must be collected as postmarketing surveillance.

Heartsheet®, by Terumo Corporation. The autologous skeletal myoblast sheets for severe heart
failure due to ischemic heart disease, obtained a 5 year conditional approval in September 2015. It
had demonstrated probable benefit in one multicenter, open-label, single-arm, feasibility study with
7 patients. The ongoing postmarketing study will include 60 patients in the product arm and 120 in
the control arm. 7

7

Jokura et al. Comparison of the new Japanese legislation for expedited approval of regenerative medicine productswith the existing systems in the USA and EuropeanUnion. J Tissue Eng Regen Med 2017.

18

In 2015, based on the Japan Revitalization Strategy and the Health and Medicine Strategy, theMinistry of Health Labor and Welfare (MHLW) launched a project to lead the world in the practicalapplication of innovative products. The strategy included an advanced review designation system
named “Sakigake” for pharmaceuticals, medical devices, and regenerative medical products
targeting revolutionary therapeutic methods, and promising large improvements over existing
therapies.

Sakigake designation is based on initial clinical trial data (phase I or early phase II trials). The
designation streamlines procedures for consultation and review: It grants priority for clinical trial
consultations, and the review time of the marketing application dossier is halved, with the aim ofbringing the products into use as promptly as possible.

Other major regions, like US and Europe have also implemented specific schemes for regenerative
medicine (ATMPs in Europe; RMAT in USA). Accelerated approval pathways and designations by
their regulatory agencies (“Breakthrough therapy” at FDA; “PRIME, Priority medicine” at EMA),
are on-par with Japanese Sakigake. All these mechanisms enable expedited access to the market
under conditions of demonstrated early clinical efficacy and safety.

Table3.2: Sakigake comparison with other regulatory designations for expedited approval

Source: PMDA

Table 3.2 below, shows the products that have received Sakigake designation by the JapanesePharmaceuticals and Medical Devices Agency (PMDA) in the two rounds of assignment held so far(2016, 2017)19

Table 3.3: Sakigake designations for regenerative medicine products 2016-2017.
1st round of Sakigake designations: Medical Devices & Regenerative Products, as of Feb. 2016
Product name

Proposed indication

Name of Applicant

Titanium Bridge

Adduction-type spasmodic

Nobelpharma Co. Ltd.

(Hinge type plate with Ti)

dysphonia

Bioresorbable adhesion barrier

Postoperative adhesion

Otsuka Pharmaceutcal(THN-01 trehalose solution)

prevention

Factory, Inc.

STR01 autologous bone marrow

Nerve syndrome and dysfuction

NIPRO Medical Co., Ltd.

derived mesenchymal stem cell

due to spinal chord injury

G47 Growth controlled oncolytic

Malignant glioma

herpes simplex virus type 1

Daiichi Sankyo Co. Ltd
The University of Tokyo IMSUT

Autologous cardiac progenitor

Paediatric congenital heart

Japan Regenerative Medicine

stem cells

disease (single ventricle)

Co. Ltd.

2nd round of Sakigake designations: Medical Devices & Regenerative Products, as of Feb. 2017
Product name

Proposed indication

Name of Applicant

Oral mucosa derived esophageal

Re-epthelialisation after

CellSeedcell sheet

extensive endoscopic submucosa(Tokyo Women’s Medical

dissection in esophageal cancer

University Hospital)

Dopamine neural precursor cell

Novel therapy inducing

Sumimoto Dainippon Pharma

derived from non-autologous iPS

dopamine discharge to mitigate(Kyoto University CiRA)

cellneural symptoms in Parkinson

Pluripotent progenitor cell

Novel therapy for improving

Healios K.K. in Japanderived from human allogenic

functional impairment caused byAthersys Inc.(US company)

adult bone marrow. (stem cell

acute brain infarctionsuspension)

It is noticeable that most products were originally “seeds” from Japanese Universities, and theirdevelopment involves collaboration between academia and a private company. Sakigake regulatory
designation program explicitly indicates that the product should be of Japanese origin, or include
Japan in the first countries where it is developed.
Athersys, a US company, has set a precedent being the first overseas company to obtain a Sakigake
designation for the regenerative medicine product that it co-develops with the Japanese bioventure
Healios KK (see page 75). European SMEs pursuing an accelerated approval in Japan, may consider
a partnership with a local Japanese bioventure to access Sakigake streamlined procedures with
PMDA.

20

4.

Japan Science and Technology Indicators

With 3.35% of the country gross domestic product (GDP) dedicated to R&D, Japan ranks among theworld’s most R&D-intensive countries8.
Total R&D expenditure was 18.9 trillion yen (€14.5 Billion) in 2015. In 2017, Japan Science andTechnology Indicators9 show that the R&D expenditure and the number of researchers in Japan, isthe 3rd largest in the world (after US and China).
However, public R&D expenditure is modest in Japan, especially in light of its high gross domestic
expenditure on R&D dominated by private sector contribution, which has made the country a worldtechnology leader.
Figure 4.1: R&D expenditure in selected countries.

Source: NISTEPIn international comparison, Japan government budget for R&D (0.65% of GDP) ranks sixth, behind
Korea (1.21%), China (1.02%), Germany (0.88%), US (0.80%) and France (0.63%).
Figure 4.2: Changes in government budget for Science and Technology as percentage of GDP

8

OECD 2015
Japanese Science and Technology Indicators 2017, August 2017, Research Unit for Science and Technology
Indicators , National Institue of Science and Technology Policy (NISTEP), Ministry of Education, Culture, Sports,
Science and Technology (MEXT)
921

After years of stagnant support for the sector, Japan will increase funding for science and technology
in 201810. The government’s science advisory body announced in January 2018 a total investment inscience and technology climbing to 3.84 trillion yen (28.8 billion euro), an increase by 7% comparedwith 2017. The government of Prime Minister Shinzo Abe aims to boost Japan’s science andtechnology budget by 300 billion yen (€2.28 billion) per year, to meet a goal of 1% of the country’s
gross domestic product (GDP) by 2020, up from 0.65% in 2015.
R&D funds from Japan government are dedicated to “Universities and Colleges” (41.9%) and“Other Public Organizations” (49.6%). The latter includes research institutions outside University,
like RIKEN for example11. In 2018, operational funding for national universities remains at just over1 trillion yen (€7.5 billion), the same as in 2017. Stagnant university funding follows substantial
government cuts to their budgets: about 1% a year between 2004 and 2014.7

R&D Output- Scientific publications
In terms of R&D output, looking at the number scientific research papers, Japan ranks 4th in theworld (after US, China and UK) and 9th on scientific publications with high citations (after US,
China, UK, Germany, France, Italy, Canada and Australia).7
Looking at the last decade, the Japanese share of worldwide publications has dropped, unlike thoseof South Korea and China. Japan's share of high-quality papers has also declined. This is a concern
recurrently voiced by Japanese research institutions leaders.
Figure 4.3: Number of top 10% cited papers as a proportion of total papers by country. 11

Source: NISTEP

1011Nature article https://www.nature.com/articles/d41586-018-01599-w
http://www.nistep.go.jp/wp/wp-content/uploads/NISTEP-RM261-Summary_E.pdf

22To explain this loss of influence, some signal the abolishment of fundamental basic research at thecore of big Japanese corporations. Others believe that it is the natural result of austerity in publicscience funding12, and point to a structural problem in the budgetary system of public research: Inorder to access public funding, the majority of researchers are forced to join calls issued by thegovernment with a pre-established subject of research. Such system precludes researchers to pursue
investigations based on their own original center of interest13
Figure4.4: Evolution in Japan R&D spending and share of highly cited papers12

Source: Nature

NISTEP suggests that Japan's scientific knowledge is possibly not being sufficiently utilized by its
own technologies, noting that while the number of papers in "clinical medicine" has been increasing,
the share of “biotechnology/pharmaceuticals" in the number of patent families is low.

12

nature https://www.nature.com/articles/543S10a

13

personal communication, Prof. Matsumoto, RIKEN president conference at the EU-delegation, January 201823

Japan has the world's second most Nobel Prize laureates in life sciences, in the 21st century14
Table 4.1: Japan Nobel Prize laureates in life sciences

1981

Kenichi FUKUIKyoto University

for their theories concerning the course of chemical reactions

2001

Ryoji NOYOR

Nagoyafor their work on chirally catalysed hydrogenation reactions

University
2002

Koichi TANAKA

Shimazu corp.

for their development of soft desorption ionisation methods for mass
spectrometric analyses of biological macromolecules

2008

Osamu

Bostonfor the discovery and development of the green fluorescent protein, GFPSHIMOMURA

University

2010

Akira SUZUKI
Ei-ichi NEGISHI

Hokkaido
University

for palladium-catalyzed cross couplings in organic synthesis

2012

Shinya YAMANAKA

Kyoto University

for the discovery that mature cells can be reprogrammed to become
pluripotent

2015

Satoshi OMURA

Kitasato

for their discoveries concerning a novel therapy against infections causedby roundworm parasites

University
2016

5.

Yoshinori OSUMITokyo Institute ofTechnology

for his discoveries of mechanisms for autophagy

European Union-Japan Cooperation on Health

The EU and Japan cooperate in multilateral initiatives 15 aimed at addressing global healthchallenges. These are in particular the International Human Epigenome Consortium16 (IHEC), the
Human Frontier Science Programme Organisation (HFSP)17, the International Human Microbiome
Consortium (IHMC)18, the International Cancer Genome Consortium (ICGC)19, and the International
Mouse Phenotyping Consortium (IMPC)20.
The Japan Agency for Medical Research and Development (AMED)21, launched in 2015, represents
an important interlocutor on health research cooperation with Europe. AMED has joined theInternational Rare Diseases Research Consortium (IRDiRC) 22 and the Global Research
Collaboration for Infectious Diseases Preparedness (GloPID-R)23, as well as the Global Alliance for
14

Source: The Japan Association of National Universities/ Nobel prize HP
Roadmap for EU-Japan ST cooperation- EC October 201716 http://ihec-epigenomes.org/
17 http://www.hfsp.org/
18 http://www.human-microbiome.org/
19 http://icgc.org/
20 http://www.mousephenotype.org/
21 https://www.amed.go.jp/en/index.html
22 http://www.irdirc.org/
23 https://www.glopid-r.org/
15

24

Chronic Diseases (GACD)24 . These initiatives will constitute the frame to ensure cooperation
between the EU and Japan in the future via regular meetings among members.

AMED has a permanent representation in the UK. On bilateral agreements, AMED signed a MoU
with Spain in 2017, and in March 2018 the first Joint funding call was launched for collaborative
research (Japan-Spain) in early stage nanomedicine projects25.

There is further scope for cooperation through the European and Developing Countries Clinical
Trials Partnership26 (EDCTP). An area where cooperation might be strengthened is anti-microbial
resistance, in the frame of the Joint Programming Initiative on Anti-Microbial Resistance which
Japan joined in 2016.

Japanese researchers, universities, research organisations and enterprises can team up with European
partners to participate in projects under Horizon 2020. As a high-tech country, well advanced inresearch and innovation, Japanese participants are, however, not automatically funded throughHorizon 2020. Japanese participants have to determine themselves the sources of funding and findthe resources for their part of the project. These may be own funds, as well as funds received fromJapanese ministries, agencies, foundations and other organisations that fund research and innovation
activities in Japan.
One way to implement the targeted opening of Horizon 2020 to third country participants is through"coordinated calls", which are organised jointly with funding organisations from third countries. Thishas worked well with Japan for nine calls during the period 2011-2017 in the fields of ICT and ICT
robotics/health (with the Ministry of Internal Affairs and Communications - MIC - and the National
Institute of Information and Communications Technology of Japan - NICT).

24

https://www.gacd.org/
http://www.idi.mineco.gob.es/stfls/MICINN/AEI/ficheros/Japan_Spain_Nanomedicine_Call.pdf
26
http://www.edctp.org/
25

25

6.

Industry- Academia Collaborations in Japan.

Industry-Academia collaboration has evolved in Japan in order to facilitate interactions between thetwo institutions. Until 1980, restrictive government regulations caused levels of collaboration toremain low. After the introduction of the 1995 Science & Technology Basic Law, and theTechnology Licensing Organisation (TLO) Act, the level of interaction improved.

Japan National universities used to be government organizations until 2004, when they became
independent agencies. With their incorporation, national universities increased their degree of
freedom in activities such as investment on Technology Licensing Organizations (TLOs) andpossession of patents. Universities can be officially the owner of the IP generated by its researchers,
and TLO is the operating arm that performs technology transfer activities on behalf of or together
with the University. For more information on the nature and characteristics of technology transfer
system and TLOs in Japan, see the report by Luca Escoffier published in 2015 by the EU-Japan
Centre for Industrial Cooperation.27

In 2006, the amendment of the Basic Act on Education meant that contribution to society, including
university-industry collaboration, was placed as one of the principle missions of universities alongwith education and research.

From 2008 to 2013, METI supported establishment of facilities of potential strongholds, in major
regions, where Industry-Academia-Government get together “under one roof” in order to bridge
leading technologies in the region for practical development.

27

Japan’s Technology Transfer System: Challenges and Opportunities for European SMEs

26

Figure 6.1: Industry Academia Collaboration Promotion Policy in Japan 28

In 2013, based on the Industrial Competitiveness Enhancement Act29, National Universities started
to be allowed to invest equity in university- originated start-up companies.

In 2016, Japan Revitalization Strategy decided by the Cabinet, set the following governmental goal:“Tripling the investment value from companies to universities and national R&D institutes by 2025
to surpass the average investment level of other OECD member states”.
In light of that goal, METI and MEXT recognize the importance of fortifying related systems inuniversities to deepen the industry-academia collaboration. To this end, the ministries jointly
established the Council of Industry-Academia-Government dialogues for the promotion of
innovation.
Guidelines were issued in November 2016, clarifying the prescriptions to strengthen the
Industry-Academia-Government collaboration activities30, from the perspective of Industry.

https://www.rieti.go.jp/en/events/bbl/16110101_watanabe.pdf https://www.rieti.go.jp/en/events/bbl/16110101.html
29
http://www.meti.go.jp/english/press/2016/1130_001.html
30
http://www.meti.go.jp/english/press/2016/pdf/1130_001a.pdf

27

Figure 6.2: Guidelines for enhancing Academy-Industry-Government Collaboration activities

Collaborative Research
While license agreements on the use of university technologies are a common way of knowledgetransfer between research institutions and companies, contractual research is also a major channel ofuniversity-industry collaboration in Japan31. Research results from such cooperation contracts arelikely to be licensed smoothly because there is already an industrial partner, and industrial property
rights are at the center of the contract negotiation process.

If a company, or any organization, wants to have a formal research collaboration agreement with anational university in Japan, then it has to enter into either a joint research contract orcommissioned research with the university.

- Under joint research, the University receives funds and researchers mainly from private
firms to conduct research on common projects. Researchers from private companies areallowed to work at the University premises.

31“Academic Patenting in Japan: Illustration from a Leading Japanese University” by Makiko Takahashi, René
Carraz. http://www.beta-umr7522.fr/productions/publications/2009/2009-07.pdf

28

- Commissioned research contracts involve governmental agencies in 80% of the cases(rather than private firms), or private companies under a national project scheme.

In Japan the ratio of corporate research and development (R&D) investment in domestic universities
is less than 1% of the total corporate R&D budget. For comparison, OECD data for 2013 report a
3.73% ratio in Germany, and 1.7% in the UK. The expense of each industry-academia collaboration
remains small, less than $30,000, compared to some other countries (in the US it averages around 1
Million US$)32.

Specific data on the life sciences industry-academia linkage in Japan, published in 2007 byProfessor Kneller33 from the University of Tokyo, show that only 18% of life science inventions
arise under joint research, and of these, only one third involve large companies (the remaining
arising from joint research with start-ups or other small companies). The situation in the Japaneselife sciences sector is different from other fields, such as engineering, chemicals and IT software,
where joint research with large Japanese companies, usually accounts for a much larger proportionof inventions.

32 https://www.rieti.go.jp/en/events/bbl/16110101_watanabe.pdf
33 Kneller, R. J Technol Transfer (2007) 32: 435. https://doi.org/10.1007/s10961-006-9024-9 The beginning ofuniversity entrepreneurship in Japan: TLOs and bioventures lead the way

29

7.

Entrepreneurship and policies supporting Bioventures in Japan

Business start-up rates for all fields are quite low in Japan (around 5% compared to 14 % and 12 %in UK and France respectively). The proportion of population with entrepreneurial motivation lags
behind in Japan (around 23%) compared to USA (77%), Germany (69 %) or France (61%).34.

On academic entrepreneurship, the year 2000 law to strengthen industrial technology is considered
to have facilitated start-ups foundation, by enabling university researchers to consult openly forcompanies and to manage ventures. 35

In fiscal year 2017, the number of start-ups created to commercialize results of R&D from Japanese
Universities rose by 13% according to METI surveys 36 , surpassing a total of two thousandcompanies for the first time, with 2093 university- based startups.

Figure 7.1: Trend in the number of university based start-ups in Japan

Source: METIThe biggest category of university ventures are bio, healthcare and medical equipment start-ups(659), followed by IT applications and software (614 start-ups)37.
The number of biotech, healthcare and medical equipment start-ups has increased a 13%, in fiscal
year 2017, with 86 new bioventure companies created. Survey data show that this category was also
the one with highest growth.

34

NISTEP
Kneller http://www.kneller.tokyo/pdf/New_Japanese_technology_transfer_system_and_entrepreneurship.pdf
36
http://www.meti.go.jp/press/2017/03/20180309007/20180309007.html; Full report (in JP)
http://www.meti.go.jp/press/2017/03/20180309007/20180309007-1.pdf
37
NIKKEI Asian Review, March 9, 2018.
35

30

Figure 7.2: Number of university based start-ups in Japan, per sector

IT (software and apps)
IT (hardware)
Bio/ Healthcare/ Medical equipment
Environmental technology/Energy
Chemicals and materials science (excluding bio)
Manufacturing (excluding IT hardware)
Other services

METI launched in March 2018, a new online university venture database, which at the time of
finalizing this report was still under construction. The database was expected to include informationon the ventures creation, company data on major investors and alliances, as well as company
expectations for overseas expansion.38

In terms of venture capital investment worldwide, biotech is the second field receiving more funds
Figure 7.3: Worldwide Venture Capital investment distribution by industrial sector

Source Thompson-Reuters
38
39

39

http://www.meti.go.jp/policy/innovation_corp/univ_startups_db/
PwC/NVCA MoneyTreeTM Report, Data: Thomson Reuters (from UTEC presentation Feb 2017)31

In recent years, the government of Japan has acknowledged the importance of biotechnology
innovations for economic growth, and the driving force role of healthcare ventures as a vehicle thatwill be key to the success or failure of innovation.

In 2016, the Ministry of Health Labour and Welfare (MHLW) sponsored a "Roundtable on
promotion of venture businesses responsible for medical innovation". It was realized that despite
its high potential due to excellence in research and number of seeds, Japan medical venturedevelopment was lagging when compared to situation in western countries. Problems identified
concerned three main areas:-

Human Resources: Scarcity of entrepreneurs and people with necessary skills. Low movement
between academia-industry-government.

-

Financial: Lack of financial support for venture businesses-

Weak connection with overseas, low visits inbound and outbound“Make Medical Ventures a Driving Force for Innovation!”40, was the title of the report thereafter
issued by MHLW in July 2016 , prescribing promotion measures to be put in place to “incentivize
medical venture blossom”. The main actions cited in the report include the construction of a
“Venture Support System” at MHLW as well as at the Pharmaceuticals and at the Medical Devices
Agency (PMDA). MHLW responds to questions from ventures on R&D, regulatory aspects on
conduct of research, and overseas development. PMDA is providing specific consultation
procedures on R&D strategy, with a 90% fee discount for the venture biotech business and academia.
In October 2017, MHLW organized the first Japan Healthcare Venture Summit, taking place
within BioJapan exhibition, one of the biggest biotechnology trade fairs in Japan (see page 90).
Bioventures present at the Summit41, around 60 companies, were start-ups arising from universities,
or young ventures originating as spin-offs from pharmaceutical companies. The full list ofcompanies exhibiting at the Summit is presented in Annex 1 to this report (see page 92).
In November 2017, the Bio-Industry Division, Commerce and Service Industry Policy Group, incharge of the relevant policies on Bioventures at METI, announced the establishment of a Study
Group to discuss how to enhance the competitiveness of the drug development industry by
improving the environment in which bioventures are able to raise funds42.
According to METI, the comparison between number of shareholders of listed biotech venturebusinesses Japan and the United States shows that individual investors account for the majority of40

http://www.mhlw.go.jp/english/dl/20160729.pdf
http://www.jhvs.jp/en/index.html
42
http://www.meti.go.jp/english/press/2017/1113_003.html
41

32

these shareholders in Japan, while institutional investors account for the majority in the US. METI
estimates the market value of Japan listed bio-venture businesses at approximately 1 trillion yen(€7.6 billion), which is lower than the figures not only from western countries, but also from other
Asian countries.
Specifically, METI promotes the Study Group with the objective to:-

Encourage dialogues between Japanese and Overseas investors with domestic bioventures-

Streamline processes and minimize obstacles for bioventures listed on Tokyo Stock
Exchange Markets (Mothers and JASDAQ) in Japan-

Discuss approaches to drafting and implementing necessary policy measures.

Support from the government of Japan for the development of bioventure ecosystem is a trend set tocontinue in 2018. In the budget for MHLW for fiscal year 2008 (April 2018-March 2019) 7.3
billion yen (€54 Million) are allocated to this end.

In conclusion:
Entrepreneurship has been positioned as crucial for innovation in Europe, and certainly the same istrue for Japan and other Asian countries. More than ever before, programs to promote
entrepreneurial ventures and startups are being implemented through industrial, academic andgovernment collaboration in Japan.
Japanese bioventures are developing services, including support to drug developers, typically inscreening, synthesis, non-clinical pharmacology, pharmacokinetics, and safety assessment. The
externalization of these R&D activities provides more flexibility to pharmaceutical groups, and also
a richer source of seeds.
The bioventures being created may contribute to the establishment of a new ecosystem in the Japanesepharmaceutical industry and biotech field. This transition towards a less integrated model ofpharmaceutical companies in Japan may open new possibilities for European SME companies
providing technologies and services to Japanese drug developers.
Potential partnerships between European biotech SMEs/ startup companies, and Japanese bioventures
may be worth exploring, looking for synergies between technologies and potentially enabling an
expansion of the client base for both sides. Partnering with a local Japanese bioventure may enable forexample, a European start-up to approach MHLW or PMDA more easily for regulatory consultations
and questions on product development requirements in Japan.

33

8.

Japan Academic Landscape- An Overview

A comprehensive description of all the biotechnology research laboratories in Japan, which areengaged in basic science and applied research, was beyond the scope of this report. A selection ofuniversities and research institutes is presented, based on criteria that a priori would favour theirapproachability by European SMEs and clusters: the support they receive for internationalisation
projects, the support from the university in creation of academic ventures, or their track record ofcollaborative research with biotech companies and pharmaceutical industry.
Research for this report was performed in 4Q2017-1Q2018. News on collaborative research
published during that period by Japanese specialised media, like “Nikkei Biotech online” and“Pharma Japan Web” will also have influenced the inclusion of certain institutions in the report.

To illustrate the potential of innovative technology applications developed in Japan, examples of
relevant bioventures, originated based on research seeds by academia, are described at the end ofeach section, mapping the origin of bioventure companies. The examples include recently
established academic ventures, as well as some commercial stage companies, which originated as
bioventures, and today have marketed products or clinical stage projects. Some of the bioventures
have become public companies, and are listed in Tokyo Stock Exchange Market, most often on the
Mothers or the Jasdaq indexes.
Japan has 86 national universities (annex with list). Each university is expected to conduct
operations with independence, developing their own unique style of education and research.
Internationalization of Japan Universities: Japan Top Global Universities Project
To strengthen the international competitiveness and compatibility of Japan’s institutions of higher
education, the Japan Society for the Promotion of Science (JSPS) in coordination with MEXT, gives
priority support43 to 13 world class universities designated as “top type” that proactively carry out
collaborations with top-level institutions overseas and engage in thorough reforms toward
globalization of their institutions.

43 https://tgu.mext.go.jp/en/universities/index.html

34

Table 8.1: List of Japan Top Global Universities (as of January 2018)
Top Global University

Internationalization initiative

Hokkaido University

Hokkaido Universal Campus Initiative. Collaborate with the World

Tohoku University

Tohoku University Global Initiative

University of Tsukuba

Transforming Higher Education for a Brighter Future through transborder University
Initiatives

The University of Tokyo

Constructing a Global Campus Model at UTokyo

Tokyo Medical and

Health for All－ TMDU initiative in creating next generation professionals for global

Dental University

health promotion

Tokyo Institute ofEnhancing Tokyo Tech Education and Research Quality through Administrative Reforms

Technology

for Internationalization

Nagoya University

Asian Hub University contributing to a sustainable society in the 21st century

Kyoto University

Japan Gateway: Kyoto University Top Global Program

Osaka University

Global University "World Tekijuku"

Hiroshima University

Hiroshima University Global Campus Expansion and Innovation Initiative

Kyushu University

Strategic Hub Area for top-global Research and Education, Kyushu University

Keio University

Enhancing Sustainability of Global Society through Jitsugaku (Science)

Waseda University

Waseda Goes Global: A Plan to Build a Worldwide Academic Network that is Open,
Dynamic and Diverse

World Premier International Research Center Initiative (WPI)44
WPI was launched by the Ministry of Education, Culture, Sports, Science and Technology in 2007,
based on the 3rd science and technology basic plan (issued by the Cabinet in 2006) with a mission tocreate globally open and appealing centers of research that serve as pivotal hubs forinternational researchers circulation.
The program has four basic objectives: advancing leading-edge research, establishing international
research environments, reforming research organizations, and creating interdisciplinary domains.
Under the Program's second phase, started in 2017, new centers are being launched
Within the biotech life sciences area, we can highlight the following centers which have been
selected by the government to take part in the WPI initiative44

http://www.jsps.go.jp/english/e-toplevel/

35

Table 8.2: WPI research centers related to healthcare biotechnology
Kyoto University

Institute for Integrated Cell-Material Sciences (iCeMS) (see page 50)

Osaka University

Immunology Frontier Research Center (IFReC) (see page 58 )Nagoya University

Institute of Transformative Bio-Molecules (ITbM)45
ITbM is world-leading molecular research institute for designing and synthesizing
molecules directed towards the discovery, visualization, and manipulation of
biological systems. ITbM will be establishing a consortium in April 2018 tobuild a network between industries in ITbM.

Kanazawa University

Nano Life Science Institute (NanoLSI) selected for WPI in 2017, aims foracquiring a fundamental understanding development, disease and aging throughtransdisciplinary research of Nanometrology, Biological, Medical, Pharmaceutical
Science, Supramolecular Chemistry and Computational Science.

Figure 8.1: World Premier International Research Center Initiative45

http://www.itbm.nagoya-u.ac.jp/en/news/2017/08/itbm-consortium.php

36Industry-Academia track record of collaborations
The table below lists the Japanese universities with receiving higher income from collaborative
research with Industry (in all fields confounded)
Table 8.3: Ranking of universities receiving highest income from collaborations with Industry

Ranking

University Institute2014

AmountAmountRanking(in thousand JPY)(in Million €)in 2013

1

University of Tokyo

4.840.830

36.45

2

2

Kyoto University

4.792.490

36.42

1

3

Osaka University

3.215.597

24.4

4

4

Tohoku University

2.743.606

20.84

3

5

Kyushu University

1.901.041

14.44

5

6

Keio University

1.585.213

12.04

6

7

Nagoya University

1.431.172

10.87

7

8

Tokyo Institute of Technology

1.409.436

10.71

8

9

Hokkaido University

994.079

7.55

10

10

Waseda University

592.542

4.5

11

Source: Adapted from Kyoto University “Research Report of Industry Academia collaborations, 2014”

University start-up creation: Accumulated number of academic ventures
The latest survey on university-originated ventures conducted by METI in Fiscal Year 2017(published in March 2018)46, ranks Japanese Universities based on the accumulated total of numberof ventures originated per academic institution.

Table 8.4 : Japanese universities by number of ventures (all fields confounded) in Fiscal year 2017. (METI)

University

Accumulated

University# Ventures

46

Accumulated# Ventures

1

University of Tokyo

245

7

Nagoya University

69

2

Kyoto University

140

8

Tohoku University

56

3

University of Tsukuba

98

9Tokyo Institute of Technology

53

4

Osaka University

93

10

Digital Hollywood Unversity

52

5

Kyushu University

81

11

Keio University

51

6

Waseda University

74

12

Hokkaido University49

http://www.meti.go.jp/press/2017/03/20180309007/20180309007-1.pdf

37

The University of Tokyo
The University of Tokyo has been ranked Japan’s top research-intensive university in every editionof the Times Higher Education World University Rankings47 since they began in 2004.
With regard to biotech applications in healthcare, we can highlight some initiatives and research
institutes from the University of Tokyo, often involved in public-private collaborative research:-

The Institute of Medical Sciences (IMSUT);-The Translational Research Initiative of the University of Tokyo;-

The Research Centre for Advanced Science and Technology (RCAST)The Institute of Medical Sciences of the University of Tokyo (IMSUT)

With its own affiliated hospital, IMSUT48 is one of the leading university-associated research
institutes for medical and life science in Japan. Focusing on infectious disease, cancer andimmunological diseases, IMSUT mission is to translate basic research findings directly to novel
drug, vaccine and medical therapies in a "bed to bench and bench to bed" approach.

IMSUT is engaged in numerous collaborative research projects with industry and academia.

For example, since December 2017 is working on a joint project with Astellas Pharma,Chiba
University

and

Asahi

Kogiosha,developpingarice-basedoralvaccine49“ MucoRice-CTB” genetically engineered to express vaccine antigens.
IMSUT is working on applications to vaccines against cholera, enterotoxigenic E. coli and viralgastroenteritis diarrhea. This is a CiCLE project, supported by the Japan Agency for Medical
Research and Development (AMED).

Another example of collaborative research with Industry, are the results published in March 2018, on
the development of a prototype diagnostic kit for bladder and hepatic cancer with Abott Laboratories(US), based on an antibody specific to laminin γ2 monomer discovered at IMSUT Division of cancer
cell research.50
47

https://www.timeshighereducation.com/news/times-higher-education-japan-university-rankings-2017-results
http://www.ims.u-tokyo.ac.jp/imsut/en/49
http://www.ims.u-tokyo.ac.jp/imsut/files/171206e.pdf
50 http://www.ims.u-tokyo.ac.jp/imsut/files/180213e.pdf
4838

In 2018, calls for collaborative research51 have been issued by IMSUT covering three main researchareas:-Development of Cutting Edge Medical Therapies-

Genome/Cancer/Disease Systems Biology-

Infectious Diseases and Immunology

IMSUT has international cooperation agreements with multiple countries, including in Europe theInstitut Pasteur (France). In 2015 the University of Tokyo established a New York based office,and one year later, IMSUT co-organized the symposium "Tokyo - New York Stem Cell Summit"
with the New York Stem Cell Foundation.

The Translational Research Initiative by the University of Tokyo

The University of Tokyo has set up an initiative to oversee translational research (TR)52 activities,
under sponsorship of MEXT initiative. In TR, fundamental science results are bridged to clinicalapplications.
In addition to drug development, the initiative includes also TR in medical devices, regenerative
medicine, and research on platform technologies for medical applications

The TR initiative includes a dedicated Translational Research Advancement Center (TRAC)
managing the assessment of seeds and industrial property (IP) rights, as well as the formation of
networks both internally and with external organizations and companies. The initiative extends todepartments and laboratories conducting TR-related research.

The center is open for cooperation with the industry and promotes developing solutions andservices to match the needs of each organization so as to turn research into practical applications.
It supports the process leading to commencement of clinical trials, and then the clinical research
center takes over.

A Cell Processing Center CPC established in 2007, is also part of the available infrastructure, as
well as the Medical Science and Research Hospital.

51
52

http://www.ims.u-tokyo.ac.jp/imsut/en/lab/organization/
http://plaza.umin.ac.jp/tri-u-tokyo/en/index.html

39

The CFTV is a core facility for GMP preparation of viral vectors for gene therapy.
The department of cell processing and transfusion operates the clinical cellular engineering facility
and manufactures cells necessary for regenerative treatments and cell therapy, as well as cells forresearch purposes.

Facilities can be used by researchers from outside the University of Tokyo, and the center is also
open to contracted research from Industrial partners. The center can also offer support in:-

Investigational product manufacturing-

Consultations on Regulatory Affairs with PMDA, MHLW (on R&D strategy, IND
application, pharmaceutical affairs…)-

Clinical protocols. Data center tasks, etc.

Examples of ongoing research are described in the website, including projects for which the
University is currently seeking for industrial partners53.

In January 2015, the TR Initiative and the U.K. Medical Research Council technology transfer
division (MRCT) concluded a memorandum of understanding on joint research. Accordingly,
antibody preparations and small molecule drug products from UTokyo were adopted as MRCT drug
development projects.

The TR initiative is supported by a promotion fund from corporate sponsors which includes major
pharmaceutical companies:
Asahi Kasei Corp.

Novo Nordisk

Eisai Co., Ltd.

Sanofi K.K.

Mitsubishi Tanabe

Shionogi & Co.

MSD K.K.

Sumitomo Dainippon Pharma

Novartis Pharma

TakedaIn February 2018, the TR initiative held a symposium on the future new possibilities of innovation

funding. It included presentations of alternative models by:

53-

Italian Fondazione Telethon, as a granting agency for the development of orphan drugs.

-

The GHIT fund (see section 9) on global health development and partnering models.

-

Crowd funding clinical research via READYFOR Inc. platform-

UTEC venture capital operation fund by the University of Tokyo (see page 42)

http://plaza.umin.ac.jp/tri-u-tokyo/en/about/index.html

40

The Research Centre for Advanced Science and Technology (RCAST)
Since its founding, The Research Centre for Advanced Science and Technology (RCAST)54 has
pursued interdisciplinary research activities in a wide range of areas based on four principles: aninterdisciplinary approach, mobility, an international perspective, and openness. Details of its
Industrial partnership coordination unit are available online55.

As an example, in January 2018, RCAST announced a collaborative research agreement fordeveloping a personalized cancer vaccine56 with the Kanagawa Cancer Center in Yokohama andBrightPath Biotherapeutics57, a clinical stage biopharmaceutical company based in Tokyo. The
collaboration consists of genomic, proteomic and immunology research, promising to lead to thenext phase of clinical studies for a fully personalized cancer vaccine.

54

http://www.rcast.u-tokyo.ac.jp/index_en.html//www.rcast.u-tokyo.ac.jp/IAG/index_en.html
56
http://pdf.irpocket.com/C4594/UV5D/wApI/wDyM.pdf
57 https://www.brightpathbio.com/english/
55

41

The University of Tokyo- Organisation of the Collaborations with Industry
The Division of University Corporate Relations (DUCR)58 works to promote collaborations between
Tokyo University researchers and society. Around 1600 public-private projects have already takeplace. DUCR also works on projects with overseas institutions and international organizations.
It is possible to search online the University Corporate Relations (UCR) database59 which includes
proposals for collaborative research. The database is searchable by key words and by categories(including Biotechnology and Medical and Pharmaceutical Sciences). Inquiries can directly be sent
through an online form.

Figure 8.2: University Corporate relations database of proposals- University of Tokyo

Support to venture companies at the University of Tokyo
The University of Tokyo conducts venture support through cooperation with the University of Tokyo
Edge Capital Co., Ltd. (UTEC), The University of Tokyo Cooperative Platform Development Co.
Ltd (UTokyoIPC), and TODAI TLO, Ltd. an organization in charge of technology transfer activities.

The University of Tokyo has already created more than 250 university-related ventures, and theirmarket capitalization exceeds 1 trillion yen (€7.6M).
5859

http://www.ducr.u-tokyo.ac.jp/
http://proposal.ducr.u-tokyo.ac.jp/cgi-bin/ccr_usr/EN/srch_bunya.cgi?bunya=2

42

The University of Tokyo Edge Capital Co., Ltd. (UTEC)60
Founded in 2004, as a “technology transfer operator”, this venture capital fund management operates
through investment activities in venture companies utilizing technology and human resources of
University of Tokyo and other research institutions.

By January 2018, UTEC had managed four funds totaling approximately JPY 45.6 billion (€350
million), and had invested in some 80 start-ups, 9 of which have gone public, and 10 have beenacquired in M&A transactions.

UTEC plans to continue to support the creation and promotion of start-ups making of superiorscience and technology, collaborating with universities and research institutes not only in Japan but
also around the world.
The University of Tokyo Cooperative Platform Development Co., Ltd.61
Founded in 2016, it was the second venture capital operating company owned by the University ofTokyo, to promote funding for investment in venture companies originating from Tokyo University.

Table 8.5 : Examples of companies having originated as the University of Tokyo Bioventures
PeptiDream Inc62. is one of the few Japanese biotech ventures that have growninto billion dollar companies. Its model of collaborative research anddevelopment, contributes solutions to facilitate drug discovery & testing. Core
technology is based on the peptide discovery platform system (PDPS)
developed by Prof. Suga at the University of Tokyo Research Center for
Advanced Science and Technology RCAST (see page 41).
Set up in 2006 as an academic bioventure, the company went public in 2013.
The number of license agreements signed with pharmaceutical companies
worldwide is a great example of Japan’s scientific and technological capabilities.
Strategic alliances include major pharma companies from Japan and overseas.

60 https://www.ut-ec.co.jp/
61 https://www.utokyo-ipc.co.jp/company/
62 Peptidream.com

43

In 2016, PeptiDream partnering strategy expanded to smaller companies andacademia, e.g. with JCR on brain penetrating drugs, with Modulus on use ofcomputational chemistry, with Heptares on GPCR targeting expertise and withkleo on immunooncology.

PeptiDream has labs at LiC Kawasaki (see page 80) and does joint research inneurology with Kawasaki Medical School on a novel treatment for Duchenne
muscular dystrophy (DMD).
A new spin-off (Peptistar) is expected to operate from 2019 as CMO.
Prof. Suga received the Japan venture award by Prime Minister Abe, Innovators
award in 2016, and the Japan Science Council chairman’s award in 2011, for his
promotion of Industry-Academia-Government collaboration.
GlyTech Inc.63 is a pioneer in glycoscience/glycotechnology, having establishedthe large-scale manufacturing process for highly purified and characterized
human type N-glycans, as well as the chemical synthesis of glycopeptides andglycoproteins.
GlyTech expects to play a significant role in developing innovative bio-betterswith high functionality. Its technologies can contribute to developing safer andlower-cost biopharmaceuticals.
PharmaBio Corporation64, is Japan's first private sector contract development
and manufacturing organization (CDMO) specialized in cellular and tissue
based products. The company is applying AI to perform continuous tuning of
the manufacturing process by feeding back analysis results of numerous
combinations of regenerative medicine products manufacturing related

6364

http://www.glytech.jp/en/
www.pharmabio.co.jp/en44

parameters. Is included in the designated core project of the Tokyo Area zone in
the National Strategic Special Zone.
TagCyx biotechnologies65“Xenoligo™ system” is a technology for identification of novel nucleic acidbased drugs. It enables screening of drug candidates from diverse
oligonucleotide libraries containing the highly functional “fifth base”, andstabilizing molecules using proprietary technology.
Founded in March 2007 as a spin out company of RIKEN, it is currently based at
Tokyo University, Komaba Open Laboratory. In 2016, it raised 500 million
Yen (€3.8M) financing by UTEC as a lead investor. In February 2017, TagCyx
biotechnologies signed 2 year collaboration agreement with a European
biopharma company (name not disclosed).
Molcure66
High-functional antibody drug development platform based on next generation
sequencing and bioinformatics. Funded by UTEC in 2014.

Other bioventures originating from the University of Tokyo, are not part of UTEC portfolio.
Jiksak Bioengineering, EdiGene, HanaVax and Rhelixa are interesting examples of emerging
biotech companies, based on technology from Tokyo University; Medinet is now a well-established
CMO in regenerative medicine, having started on technology from Tokyo University IMSUT.

Jiksak Bioengineering Co., Ltd., launched in February 2017, offers a drug
screening service with Nerve Organoids. The Nerve Organoid represents an invivo-like nerve structure. Jiksak develops a unique screening technology
specialized for neurodegenerative diseases (amyotrophic lateral sclerosis ALS,
Parkinson's disease, etc). Jiksak’s platform provides an efficient method toactively drive drug development and toxicity test.
Jiksak Bioengineering is actively seeking partners to develop nervous-diseasemodels with stem cells.
In January 2018, CEO Dr Kawada received the Nakatsuji Award on practicalapplication of results to industrialization and commercialization. Jiksak was
selected to receive support by New Energy and Industrial Technology
65
66

tagcyx.com/en/
http://molcure.com/

45

Development Organization (NEDO).
In February 2018, Jiksak. secured 170 Million JPY (€1.3M) from ANRI,OHARA Pharmaceutical Co.,Ltd, Essential Pharma Co., Ltd. and MediFutureCo., Ltd.
EdiGene corporation67 is a drug discovery start-up originated in 2015 from
University of Tokyo, engaged in R&D on genome editing technology that has
improved CRISPR-Cas9, and in constructing next-generation drug discovery
systems.
EdiGene co- founder Prof. Nureki, from Graduate School of Sciences,
University of Tokyo, won #2 position in Nature's 10 most popular CRISPR
papers of 2017 with his paper "Real-space and real-time dynamics of
CRISPR-Cas9 visualized by high-speed atomic force microscopy".
EdiGene is currently headquartered in Tokyo and conducting R&D from
Cambridge, MA, USA.
In December 2017, Fujifilm signed an agreement for the investment of 470
million yen (€3.5 M) in EdiGene Corporation. In the joint research with
EdiGene, Fujifilm aims to apply its liposomal formulation technologies toencapsulate ribonucleic acid (RNA) designed and developed by EdiGene.
Rhelixa Inc68. was founded in February 2015, based on technology from Tokyo
University RCAST (see page 41). Rhelixa develops analysis of genome andepigenome information (data obtained via NGS techniques) in an integrated
platform. Rhelixa’s core competence lies in providing machine learning
softwares and screening techniques for epigenetic analysis that best fits theclients’ needs.
HanaVax Inc69 is a start-up established in December 2016, developing vaccines
administered by small sprays into the nose, based on novel delivery formulations
from Tokyo and Kyoto Universities. Antigens are retained on respiratory
mucosal surfaces to initiate antigen-specific immune responses via the mucosal
immune system. A human pneumococcal nasal vaccine to prevent pneumonia,
sepsis and otitis media is under development.

67

http://edi-gene.com/
http://rhelixa.com
69
http://www.hanavax.co.jp/en6846Medinet Co. Ltd.70 originated in 1995 as a venture from IMSUT (see page 38)
pioneering research in cancer immunotherapy. Today is a listed company on
Tokyo stock exchange market. Contract cell development and manufacturing(CDMO) is its core business. It has cell processing facilities in Tokyo,
Yokohama and Osaka. According to Medinet, the size of domestic immuno-celltherapy market is about JPY10.0B (€76M), and the company holds a 20%.
Medinet in-licensed autologous chondrocyte cartilage implant NeoCart from US
Histogenics Corporation in 2017, and is conducting clinical development inJapan targeting knee cartilage defects, estimating to market by 2021. The
pipeline includes AGS-003 for the treatment of metastatic renal cell cancer andUK-based TC BioPharm’s ImmuniCell®, in which MEDINET has invested.
nmet medical needs using its proprietary technologies on CRISPR and protein

70

https://www.medinet-inc.co.jp/english/

47

Kyoto University
Kyoto University was the second university to be established in Japan, after the University of Tokyo.
It has 2700 faculty members, with two thirds dedicated to natural sciences, 18 graduate schools and
13 research institutes. Nine of the Nobel Prize laureates in natural sciences from Japan are associatedwith Kyoto University.
Kyoto Graduate School of Medicine has a strong tradition of supporting drug discovery efforts. As
an example of Kyoto seeds, nivolumab(anti-PD-1 antibody) was originated from research by Kyoto
University Prof. Tasuku Honjo and Prof. Nagahiro Minato.

In the biotech field, flagship research institutes from Kyoto University include The Center for iPS
Cell Research (CiRA) and the Institute for Integrated Cell Material Sciences (iCEMS).

Center for iPS Cell Research and Application (CiRA)

CiRA71 was officially inaugurated in 2010 with the mission of using induced pluripotent stem (iPS)
cells in new medical therapies. Directed by Dr Shinya Yamanaka, 2012 Nobel laureate for his workon iPS cells, the center is committed to research, production and shipment of high quality iPS cells
for use in regenerative medicine.
Also involved in drug discovery, in 2017 CiRA identified a potential drug candidate forfibrodysplasia ossificants progressiva (FOP).

Figure 8.3: Dr. Shinya Yamanaka at CiRA symposium for the general public on July in 2016.

CiRA researchers at Prof. Yamashita laboratory have used iPS cells to find a type of progenitor cells
that when transplanted into mice almost exclusively produced cardiomyocytes, giving these cells
great promise for future heart cell therapies.
71

http://www.cira.kyoto-u.ac.jp/e/48

CiRA is also working on the development of cell replacement therapy using iPS cells for intractableneurological diseases, mainly Parkinson's disease. In January 2018, a case of fraud and fabricateddata in a publication on Blood-Brain Barrier with Human iPSC -Derived Endothelial Cells had to be
retracted by CiRA72, and a number of measures to deter and detect research misconduct had to be
reinforced.
Since 2015, CiRA has a large-scale collaborative research program (totaling 100 researchers) with
Takeda (T-CiRA )73 aimed at new drug development for a number of diseases. T-CiRA is based at
Takeda Shonan Research Center, in Fujisawa, Kanagawa (see page 82). It receives a collaborative
funding of 20 billion yen (€151 M) over a 10-year period.

An increasing number of studies at CiRA are ongoing to bring iPS cells to clinical application.
As part of this effort, the Facility for iPS Cell Therapy (FiT) was founded within CiRA.
FiT is responsible for manufacturing clinical-grade iPS cells that will be distributed to institutes andorganizations pursing regenerative medicine.
iPS Academia Japan inc74 is acting as official iPS cell technology licensing organization (TLO) for
CiRA (and other Universities in Kyoto and other regions).It is not involved in collaborative research
agreements between the university and companies

Figure 8.3: Collaborations from iPS Academia Japan Inc.

As of September 2017, twenty-five entities from Europe had licensed from this TLO.48 Some ofthese licensees are disclosed on iPS AJ website.

Table 8.6: EU licensors of CiRA technology identified from iPS Academia Japan website
Stemnovate , Elpis Biomed, Censo biotechnologies, Newcellsbiotech, Catapult (UK)
Myriamed , Repayron, Axiogenesis, Bayer, Merck (DE)
Univercell-biosolutions, Cellectis (FR); Pluriomics (NL)72

http://www.cira.kyoto-u.ac.jp/e/pressrelease/news/150417-102717.html
http://t-cira.takeda.com/t-cira/74
http://ips-cell.net/
7349

Institute for Integrated Cell Material Sciences (ICeMS)
Founded in 2007, the Institute for Integrated Cell Material Science iCeMS75 seeks to develop
materials to comprehend cellular functions, produce materials to control processes in cells, andeventually to create functional materials inspired by cellular processes (cell-inspired materials).
ICeMS is a WPI center (see page 35)

As an example of recent results (published in Nature Biomedical Engineering in March, 2018), thegroup of Koichi Hasegawa, has developed a novel culture solution for pluripotent stem cells such as
ES cells and iPS cells, using three low molecular weight compounds that can be artificiallysynthesized without using growth factors. The material cost of the culture solution is said to be one
fifth to one tenth that of the conventional one.

Kyoto University: Industry-Academia Collaborations Organisation
According to latest data by MEXT, in 2014 Kyoto University was Japan largest recipient of private
sector research funds. Joint research funding from private sector totaled around €42 million in 2016.

Figure 8.4: Kyoto University private sector collaborative projects

Companies interested to collaborate with Kyoto University can liaise with Society-Academia
Collaboration for Innovation (SACI) 76 which aims to promote effective networks with
Universities, TLOs and private corporations, not only in Japan but also globally.

75
76

iCeMS web
http://www.saci.kyoto-u.ac.jp/wp-content/uploads/2017/03/society_academia_collaboration_method_pamphlet.pdf

50

SACI webpage47 contains up-to-date information on technology developed by Kyoto University at
various stages, i.e. patented results and also technology under research. SACI can coordinate andsupport such collaborations with the help of external organizations such as TLOs (Technology
Licensing Organizations). SACI manages the "GAP Fund Program" and "Incubation Program" tosupport the commercialization of research results of Kyoto University.77

Other types of Industry-University linkage include Endowments and Endowed laboratories(donations), Commissioned Research, and Collaborative Research. Under Collaborative research,
Kyoto University becomes an equal partner with companies in researching a particular topic bymutually providing researchers, research funds and facilities in order to produce optimal research
results. Research can be conducted at university only or both at university and industrial partner site.
Ownership of results, in terms of industrial property, is generally shared.
Figure 8.5: Collaborative research schemes at Kyoto University
There is no upper or lower limit as
to how much collaborative
research costs. Kyoto University
indicates that 35% of projects cost
between 1 and 3 million yen (7500
to 23000 euro).

More information on costs, direct
and indirect expenses, and tax
credit for collaborative projects isavailable on Kyoto University
SACI website

In the medical science field, a specific organization at Kyoto University deals with relationships with
Industry: Kyoto University Medical science and Business Liaison Organisation (KUMBL)78.
Successful collaborations initiated or supported by KUMBL include the 5 year institution level
collaborative R&D agreements signed between the Graduate School of Medicine- Medical
Innovation Center (MIC) and pharmaceutical companies Takeda, Dainippon Sumitomo Pharma Co.

7778

http://www.venture.saci.kyoto-u.ac.jp/
http://www.kumbl.med.kyoto-u.ac.jp/e/index.html

51

Ltd. and Mitsubishi Tanabe Pharma Corporation. Research agreements have also been signed with
Astellas and Canon on medical device development.79

KUMBL is also promoting the formation of ventures to exploit Kyoto university research results.
One of the programs supported by KUMBL to accelerate bioventures is KYOTO-SPARK, a
training program for ventures in translational research. The SPARK network was originallydeveloped at Stanford University (US), to showcase drug development programs that are ready forpartnering or venture funding. SPARK has a global network, with representation of the program also
taking place in several European countries (Finland, France, Germany, Italy, Norway).
SPARK biotech companies from Kyoto were presenting in Boston, US. in February 2018. Also in
February 2018, the second KYOTO-SPARK Symposium “Value of Academic Translational
Research” took place in Japan, with presentations by European start-ups like Sartar therapeutics(FI).

Figure 8.6: KUMBL organization at Kyoto University

KyotoUniversity Innovation Capital Co. Ltd.
Kyoto University was the first to adopt the “support program for utilizing specified research results”
approved by MEXT and METI based on the Industrial Competitiveness Enhancement Act, andparticipates in venture capital funds, through its own authorized Organisation
79

http://www.kumbl.med.kyoto-u.ac.jp/e/innovation/results.html

52

Kyoto University Innovation Capital Co. Ltd. (KU-iCap)80.
Founded in December 2014 as a wholly owned investment firm of Kyoto University, the venture
fund mainly invests in start-ups and early-stage ventures, which endeavor to commercialize
knowledge generated by the University’s researchers.
In a “hands-on approach”, it also provides assistance in designing a business and development plan,
and a club for matching entrepreneurs and Kyoto University technology.

Figure 8.7: Fund scheme by Kyoto University Innovation Capital Co. Ltd. (KU-iCap)

Within Kyoto University, there is a venture incubation center81 with office space. Innovation Hub
Kyoto82 provides a wet lab for the life science field. Outside the university, other facilities usedby bioventures include: Creation Core Kyoto Takuma83, Kyoto Research Park (KRP)84, and Kyoto
University Venture Plaza85.

80

http://www.kyoto-unicap.co.jp/unicap/wp-content/uploads/iCAP-PANF_en.pdf
http://www.venture.saci.kyoto-u.ac.jp/?page_id=273
82
http://www.ihk.med.kyoto-u.ac.jp/
83
http://www.smrj.go.jp/incubation/cckm/
84
http://www.krp.co.jp/
85
http://www.smrj.go.jp/incubation / kkvp /81

53

Table 8.7: Examples of Bioventures supported by Kyoto University (KU-iCap)
Stem Cell & Device Laboratory, Inc. (SCAD)86 was founded in May 2014,
with the aim of commercializing stem cell and micro/nanotechnologies
developed in the Kyoto University’s Institute for Integrated Cell-Material
Sciences (iCeMS).
SCAD has developed proprietary human cell-based devices that serve the drug
screening, safety and efficacy assay markets. SCAD-MT ™ cardiomyocyte is aquality-certified, ready-to-use nanofiber-based culturing device pre-plated withfunctional and stable human iPS cell-derived cardiac micro-tissues, characterizedwith 3D and highly oriented structures and developed for drug discovery anddevelopment, and in vitro toxicology.
Kyoto Stem Cell Innovation, Inc.87, with CEO Professor Emeritus N.
Nakatsuji, provides professional consultation services, through a global networkof technical advisors, bridging academy and industry to support joint businessdevelopment, advising and implementing the stem cell research outcomes.
Advisory services are offered to ventures and for investors interested in creating
new stem cell technology. Fund research at universities and other institutions,
including incubation and/or intermediary services for funding institutes
Chordia Therapeutics88, founded in 2017, is dedicated to drug discovery inoncology areas of high unmet medical need, combining knowledge from Kyoto
University with expertise in drug discovery. Its lead asset is a CDC-like kinase(CLK inhibitor) based on research by Professor S. Ogawa at Kyoto University
on splicing abnormalities as causative events of cancer development. CLK is akinase regulating RNA splicing.
Chordia receives support from Takeda, as other ventures based in the Shonan
Park in Kanagawa (see page 84). By end of November 2017, the company hadraised 1.2B Yen (€~9M) in Series A financing

86

Scad website
http://kyoto-sci.com/biz-e.html
88
http://www.chordiatherapeutics.com/eng/update/pdf/20171122_EN.pdf
8754

Kinopharma89 is a biopharmaceutical company, established in 2005 as drug
discovery bioventure. Develops the clinical application of kinase inhibitors thatfounder Prof. Hagiwara discovered in his academic research. In July 2016 started
an investigator initiated clinical trial with antiviral candidate compounds. In July
2017 opened drug discovery research centre at the innovation Hub of Kyoto
University Pharmaceutical research building.
Thyas Co. Ltd.90 was established in 2015, by CiRA and KYOTO-iCAP to focus
on treating cancer and other chronic diseases with T-iPSC.
Thyas is developing autologous adaptive immunotherapy with iPS derived killer
T cells for the treatment of cancers and chronic viral infections.
Kyoto Drug Discovery and Development Co., Ltd (KDDD)91, founded in
April 2015, is a spin-off company based on results of research by Kyoto
University Department of Ophthalmology and Graduate School of Biostudies. It
is working on protein modulators that would protect cells from degeneration anddeath. Neuroprotective effects on retinal nerve fibres and retina ganglion cells
have been observed in animal models. By 2016, the company had raised
430Myen (€3.2M)

Table 8.8: Other bioventures companies based on technology originating from Kyoto
University (not necessarily supported by above mentioned VC)
i-Heart Japan92 was founded in 2013 as spin-off from CiRA. In 2014 acquired
license on iPS technology, based on research by Prof. Yamashita, and enteredinto alliance with Takara bio.
Boehringer Ingelheim signed a collaborative research agreement with iHeart on
development of a cardiotoxicity test for new drug development.
In June 2016, Takara Bio Inc. started commercializing iHeart iPS cell derived
cardiomyocytes "iPSC-CM" for laboratory use. Prepared from iPS cells
artificially introduced with a drug resistance gene expressed only in
cardiomyocytes, the purity of cardiomyocytes is increased by a method of killing89

http://www.kinopharma.com
http://thyas.co.jp/en/91
http://www.kyoto-drug.com
92
http://www.iheartjapan.jp/
9055

cells other than cardiomyocytes with a drug. "iPSC-CM"can be used for
cardiotoxicity evaluation of drug candidate substances.
iHeart is also working on iPS technology based products for hearttransplantation.

In 2016 i-Heart Japan was commissioned by NEDO with a project on
functional development of 3D body tissue manufacturing.
In 2017, results of research collaboration with CiRA, supported by AMED, were
published prof. Yamashita et al. in Nature Communications, showing success inmodeling torsade de pointes (TdP) arrhythmias in in-vitro 3D human iPS cellengineered tissue. These results are expected to be applied in cardiotoxicity
testing in the development of new drugs, and to better elucidate TdP
mechanisms.
MegaKaryon corporation 93 was founded in 2011 to commercialize theresearch results of laboratories by Prof. Nakauchi (University of Tokyo) andProf. Eto (Kyoto University) on proliferating megakaryocytes from iPS cells,
opening the way to mass production of platelets.
It has signed a collaborative research with Boston Children Hospital (US).
Initially an A-STEP project supported by a program of Japan Science andTechnology Agency, by 2018 the company had raised 6240 million Yen (€47 M)
of private funds. In 2017 it presented at the US-Japan innovation awards, at
Stanford University.
ReproCELL94 was founded in 2003 based on stem cell technologies pioneeredat the Institute for Integrated Cell-Material Sciences (iCeMS) Kyoto University,(see page 50) and The Institute of Medical Sciences (University of Tokyo) (seepage 38). It offers human iPS cell derived products: cardiomyocites, neurons,

93
94

http://www.megakaryon.com/en/
https://www.reprocell.com/

56

hepatocytes, cells for diabetes research, etc.
Reprocell is working with Tokyo Institute of Technology in the production of
pancreatic progenitor cells and beta cells from iPS cells. It also has a joint
R&D agreement with Tokyo Women's Medical University on "Developmentof mass manufacturing system of Human iPS cell-derived cardiomyocyte"

In April 2011, the company established facilities in USA. ReproCELL Europe
was later established by acquiring around 2014 two university spin-offs fromthe UK: Biopta, providing human tissues to predict drug activity before clinical
trials, and Reinnervate with expertise in 3D cell culture.
ReproCELL was listed on the Osaka Securities Exchange JASDAQ GrowthMarket in 2013.
RegCell95 was founded in January 2016 within the venture incubation activities
implemented by iPS Portal Inc 96 (see page 48) based on technology byinternationally-renowned immunology researchers Prof. Sakaguchi and Prof.
Kawamoto from Kyoto and Osaka University.
Aiming to use regulatory T cells for handling immune rejection against organtransplantation and regenerative medicine, targeting autoimmune diseases andcancer, RegCell works on technology for multiplying and producing high-quality
T cells. The company is also developing culture methods for practicalapplication of such immune cells and aim for clinical application in a few years.

Reprocell received NEDO support in 2017, to create a new treatment for
suppressing inflammatory reactions associated with autoimmune diseases andallergies.
In April 2017 Fujifilm signed a business partnership agreement with RegCell on
development support of regenerative medicine products.
Myoridge97 founded in August 2016, it is based in Kyoto University (KU)
Pharmaceutical Research Institute. Applying technology licensed from KU on
protein free myocardial differentiation, Myoridge produces cardiomyocite sheetsfrom human and monkey iPS cells.

From the point of view of a European biotech Start-up considering deployment to the Japanesemarket, the case study below makes an interesting example of an entry through the establishment of95

http://regcell.jp/
http://ipsportal.com/en/about/#s05c
97 http://myoridge.co.jp/eng
9657

an office at a Japanese University:
Cellink98 is a Sweden based biotech company, commercializing bioinks for 3D
bioprinting of human organs and tissue.
Due to the high demand of technology and its rapid partnership growth within
Asia, in February 2018 the company decided to further establish themselves in
the Asian market by opening office at Kyoto University Innovation Hub99
Kyoto office will serve as a base for research, as well as facilitating relationships
with collaborators in Asia.

Osaka University
Osaka University comprises 17 Graduate schools, 6 Research Institutes and 2 University Hospitals
amongst other facilities. In the biotech area we can highlight the Institute for Protein Research, theResearch Institute for Microbial Diseases, and the Inmunology Frontier Research Centre100.
A compilation of outstanding research projects conducted by Osaka University on life science andmedicine is published annually (in English). It also describes international research projects, which
for Europe includes collaborative projects with Germany and Ireland.101

The Immunology Frontier Research Center (IFReC)
Osaka University Immunology Frontier Research Center (IFReC)102 was established in October2007 with leading immunology researcher Shizuo Akira at its head. The institute conducts research
integrating Immunology, Imaging and Bioinformatics to understand the immune system including
spatiotemporal information by developing technologies to visualize and analyse the dynamics,
activation state, and interaction of immune cells in vivo.

Such efforts are expected to lead to the establishment of new immunotherapies such as developmentof vaccines for infectious diseases based on control of immune dynamism and control of immune
reaction against cancer cell. IFReC a WPI centre has innovative approaches through theinterdisciplinary collaboration and participation of world-top immunology and imaging researchers.
98

https://cellink.com/
https://cellink.com/cellink-opens-office-kyoto-university-japan/
100
http://www.jsps.go.jp/english/e-toplevel/data/wpi.pdf
101
file:///E:/_Users/EU-Guest/Downloads/researchprofile2017_s.pdf
102
http://www.ifrec.osaka-u.ac.jp/en/99

58

IFReC is open to collaborations with Industry. Osaka University established through IFReC a
comprehensive collaboration agreement on cutting-edge immunological research activities with
Chugai Pharmaceutical Co., Ltd. in 2016103

and Otsuka Pharmaceutical Co. Ltd. in 2017. The

agreement with Chugai will provide Osaka University with 1 billion yen annually (€7.5M) for a totalof 10 billion yen (€75M) over 10 years.
Osaka University: Industry-Academia Collaborations Organisation
Osaka University has the Office for Industry-University Co-Creation, to enhance an environment
for creating innovation so that it can serve as a hub for network-type industry-university projects104.
Figure 8.8: Osaka University Office for Industry-University Co-Creation website

The website can be consulted in English, and describes the different forms of collaborative
mechanisms such as Joint Research, Commissioned Research, Collaborative Laboratories,
Scholarship donations etc. Osaka University publishes information on research seeds on a databasecalled " ResOU "105 . The university welcomes inquiries on cooperation and collaboration towardcommercialization of posted seeds.

103 http://www.osaka-u.ac.jp/ja/news/storyz/special_issue/research_topics_nl76/201706_special_issue01
104
http://www.uic.osaka-u.ac.jp/target/company/co-creation/105
http://resou.osaka-u.ac.jp/en.

59Figure 8.9: Osaka University research seeds website

As previously seen in this report with the Universities of Tokyo and Kyoto, Osaka University owns aventure capital organisation, to support creation and development of university originated ventures:
OSAKA University Venture Capital Co., Ltd. (OUVC)106.

OSAKA University Venture Capital Co. , Ltd.

Osaka University Venture Capital (OUVC) works closely with Osaka University Industry
Co-creative Headquarters (founded in 2018) , not only to commercialize the research results ofOsaka University, but also cultivating innovation human resources and entrepreneur support.

The table below lists some companies in the biotech space, which have been supported by OUVC
(including JTEC, a company gone public).

Table 8.9: Examples of Bioventures originated at Osaka University
JTEC Corporation107
Established since 1993, in partnership with Osaka Computer Industries, it
received investment from Osaka University OUVC from 2015.
Developed many joint research programs with Yokohama City univ., AIST and
Osaka university.
Itsinnovative

humanelastic

cartilage

devicecreation

using

the

three-dimensional cell culture system aiming at a clinical study was selected for

106 http://www.uic.osaka-u.ac.jp/kyoso/
10760

ACT-M program from AMED, and conducted joint research with Yokohama
City University and Kanagawa Children's Medical Center.
In January 2018 it was listed on the Market of High Growth and Emerging
Stocks (Mothers) of the Tokyo stock Exchange.
MATRIXOME, Inc.108 established in December 2015, with headquarters at
Institute for Protein Research (iFREC, see page 58), Osaka University.
It contributes to the discovery and development of regenerative medicine byproviding Laminin-E8 fragment products.
“Matrixome” is a term proposed by Professor K. Sekiguchi, from Osaka
University, describing a subset of the proteome to define whole collections of
extracellular matrix molecules that constitute the customized microenvironments
of individual cell types.
The venture develops and commercializes various equipment coated withlaminin derivative for use in cell culture technology.
FunPep109 was established in October 2013, based on technology for design,
discovery and optimization of functional peptides from Osaka University
Graduate school of medicine.
FunPep aims to commercialize "antibacterial peptides" and "antibody-derived
peptides" which are research results on functional peptides.
Targeting intractable peptic ulcer disease, as well as highly marketableantibody-inducing peptides.
Chromocenter Inc. 110 was created in 2016 based on research results ofProfessor T. Ohimasa of the Graduate School of Engineering, Osaka University,
on artificial chromosome vector as fundamental technology.
Construction of stable gene expressing cell lines, such as construction of atransgenic animal prepared and protein high producing cells are expected to be
used in a variety of applications.

108 http://www.matrixome.co.jp/en/company
109 http://funpep.co.jp
110
http://chromocenter.com/eng/?m=201707

61

KOTAI

Biotechnologies,

Inc. 111

wasfounded

in

2016

based

on

High-throughput structural modeling and analysis for immune cell sequences.
Applications in biomarkers and drug discovery.
Osaka University Immunology Frontier Research Center (IFReC) Professor
Daron M. Standley commercialized research results on "Structure modeling of
immune repertoire”
By February 2018 it had received 147 M Yen (€1.1 M) investment from OUVC.
Epigeneron, Inc.112 founded in April 2015, is based on results from Osaka
University Fujii Lab113, on epigenetics regulation and transcription, by using
locus-specific chromatin immunoprecipitation methods (ChIP) and engineered
DNA-binding molecule mediated (enChIP) technologies.
Epigeneron develops new drugs and offers services for development of
epigenetic drugs in cancer, CNS, anti-microbial drugs…

A complete list of ventures in Osaka region can be consulted on the KANSAI bioventure website view
http://www.kinkibio.com/venture/bios/index/lang:eng

An example of commercial stage biotech company, aiming to become a global leader in gene
medicine, which also originated as bioventure based on technology from Osaka University is AnGes
Inc114.
AnGes was one of the first two publicly traded venture firms in Japan to have beenlaunched by university researchers. Founded in December 1999 under the name
MedGene, its R&D focused on genetic and nucleotide based drugs. By 2002,
under the new name name AnGes Inc99, it already had facilities in USA andEurope (UK).
In January 2018, AnGes submitted a marketing application to PMDA for its leadproduct: HGF plasmid (gene therapy) for the treatment of critical limb
ischemia. It has an alliance with Mitsubishi Tanabe for this product.
AnGes has another genetic medicine in clinical development, an NFκB decoy
oligonucleotide, a specific inhibitor for NF-κB that acts as a switch to a genecluster involved in the immune inflammatory response, being developed in atopic
dermatitis and disc degeneration.
111

https://www.kotai-bio.com/
http://epigeneron.com/
113
http://www.biken.osaka-u.ac.jp/lab/microimm/fujii/top/index_e.html
114
https://www.anges.co.jp/en/
112

62

Examples of Academic bioventures from other Universities (Hiroshima, Nagoya, Hokkaido,
Kyushu, Kurume, Keio, Saitama)
A selection of interesting bioventure examples originated from other universities in Japan, arepresented in table below.

Table 8.10: Examples of Bioventures spawning from other Japanese Universities
Hiroshima University
Two cells company Ltd115. winner Japan venture awards 2018116;
Bioventure established in 2003, out of Hiroshima University. It works onregenerative medicine using Mesenchymal stem cells (MSC), which can beisolated from adult human or animal tissues such as bone marrow, adipose tissue,
umbilical cord, and synovium.

From 2008, two cells has agreements with DS Pharma Biomedical Co., Ltd todevelop and commercialize STK® 2 (Serum-free culture medium).
In 2014 opened a gMSC center (Cell Processing Center).
It has under clinical development:-a gastric cancer regenerative cell therapy "gMSC® 1" which is athree-dimensional artificial tissue of MSC in Phase III (concluded adomestic license agreement with Chugai)-"GMSC ® 2" for cerebral infarction cell therapy (has an option
contract with Otsuka)-

R & D on early treatment "gMSC® 3" and anti-renal failure drug
"gMSC® 4"

Hokkaido University
NB Health Laboratory Co. Ltd117. was established in 2006 in Sapporo. NBHL
has expertise in the generation of functional antibodies targeting G
protein-coupled receptors (GPCRs) for the treatment of cancer, infectious
diseases, metabolic diseases, pain and inflammation. It can also provide
functional mAbs targeting GPCRs for use as a research tool to accelerate your
GPCR-targeted drug discovery on a fee basis.

115

http://www.twocells.com/
http://j-venture.smrj.go.jp/index.html
117
http://www.nbhl.co.jp/
11663Keio University
http://www.iab.keio.ac.jp/en/partnership/index.html
http://www.iab.keio.ac.jp/en/about/venture.html
Metcela, Inc118. is a regenerative medicine startup founded in March 2016,
developing new treatments for heart failure based on cellular therapies fromfibroblasts. In September 2017, announced in vivo non-clinical results inrodents. With headquarters at LiC Kanagawa, it has raised JPY150M (€1.3M)
from VC and JPY 140 million(from NEDO).In April 2017 began collaborative
research with the University of Tsukuba
Human Metabolome Technologies119 is a venture that develops themetabolomics business with two core businesses of contract analysis / biomarker
discovery by simultaneous multiple metabolite analysis by CE - MS technology
developed at Keio University, by Prof. Soga.
World-leading metabolome analysis technology and metabolite library, incollaboration with Keio University Advanced Life Science Institute and Agilent
Technologies.
Biomarkers research in collaboration with diagnostic drug manufacturers andothers. HMT has a European subsidiary in Leiden (NL) and a US subsidiary in
Boston, US.

Kurume University
BrightPath Biotherapeutics120 Co. Ltd. (former Green Peptide Co. Ltd) was
originated in 2003 at Kurume University, with the mission of developing cancer
peptide vaccines, as drug discovery bioventure. Listed in Tokyo Mothers Stock
Exchange market since October 2015. Its consolidated subsidiary Advanced
Immunotherapy Co. is conducting joint research with Juntendo University on
the clinical application of iPS cell-derived rejuvenated cytotoxic T Lymphocytes.
Kyushu University
http://camiku.kyushu-u.ac.jp/lab/collaboration
Cyfuse Biomedical KK121. Established in August 2010, was selected for NEDO
project together with Kyushu University, researching on osteochondral118

www.metcela.com
119 https://humanmetabolome.com/ir
120
https://www.brightpathbio.com/english/company/index.html
121https://www.cyfusebio.com/en

64regeneration. Focused on 3D bio printing human tissue, e.g. human liver tissue
useful for drug discovery.
In 2011 signed a licensing agreement with Kyushu university on Bio 3D
printing, and started selling a 3D printer system (Regenova®)one year later.
In 2013 relocated the HQ to University of Tokyo entrepreneurs Plaza (page 42)

Nagoya University
http://www.aip.nagoya-u.ac.jp/en/industry/support/index.html
NUProtein122 is a bioventure from Nagoya University, founded in the summerof 2016, originating from a training program on venture development, wasinitially subsidized by NEDO, and later funded by venture capital.
Commercializes a cell-free protein synthesis kit, which can synthesize
membrane proteins, transcription factors, kinase enzymes, etc. without cloning.
The protein synthesis technology from NUProtein is based on the protein
synthesis function of wheat germ and adding DNA to it, skipping the cloning
process that is required when using E. coli, reducing the total protein synthesis
process to about one day.
It is currently based at Nagoya university incubation facilities.
In 2017 received a company award from Rohto Pharmaceutical Co., Ltd. andthe EY Entrepreneur of the year award.
Okinawa Institute of Science and Technology Graduate University (OIST)
Okinawa Protein Tomography123 is the first bioventure from OIST,
established in June 2014. Provides contracted research services worldwide:
macromolecular imaging service including proteins in various states at thesingle molecule-level by combining Cryo Electron Microscopy and a
specifically designed 3D reconstruction software. Analysis of proteins and/or
complexes in biological samples.
Saitama University
Epsilon Molecular Engineering124 was established in August 2016 as abioventure from Saitama University, designing next-generation antibody
molecules, peptide aptamers against drug discovery target (in joint research,
alliance or contract business). Also sell a cDNA display screening starter kit.
Drug discovery using next-generation antibodies and aptamers against GPCR.

122

http://nuprotein.jp/en/
www.okinawa-pt.com
124
http://www.epsilon-mol.co.jp/#aboutus
123

65

RIKEN Research Institutes
RIKEN is a top-class research hub at the heart of scientific research in Japan, its largest
comprehensive research institution and a world leader in a diverse array of scientific disciplines,
with strong focus on life sciences. Central to RIKEN’s success is the collaboration and support
between its many centers, distributed within Japan and abroad, laboratories, and state-of-the-art
research facilities. The institution celebrated its century of existence in 2017.

Detailed information and contacts for each laboratory is available on RIKEN webpage, which can beseamlessly navigated in English. The selected institutes below will give an overview of potentiallyinteresting collaborative research in biotechnology, and illustrate some of the venture companies
recently created as spin-offs with technologies from RIKEN.

RIKEN activities can be divided into
four main categories: Research
Infrastructure, Strategic ResearchCenters, Chief Scientist Laboratories,
and a Cluster for Industry Partnerships(CIP).

Flagship research centers in life
sciences and biotechnology include
Bioressource Centre (BRC) in
Tsukuba, the Center for
Developmental Biology (CDB) in
Kobe, the Quantitative Biology
Center (QBic) in Osaka , and theCenter for Integrative Medical
Sciences.

66

RIKEN BioResource Center (BRC), established in Tsukuba in 2001, is one of the world’s mostimportant repositories and distribution centers of biological resources. It handles a wide range ofexperimental animals, plants, cell lines, genetic materials, microbes, and associated bioinformatics tocontribute to the international scientific community. It is particularly notable for providing humaninduced pluripotent stem cells (iPSC).

Figure 8.10: Illustration on different bioressources provided by the BRC Divisions

The bank has a wide range of disease-specific iPS cells that have been generated from patients withvarious disease backgrounds.
Further to an agreement signed in January 2018, iPSC from the bank are provided to academic andindustrial clients through ReproCELL as preferred supplier for cell differentiation into functional
cells such as neurons, cardiomyocytes, hepatocytes and others, specific to the client's request (seepage 48).

The RIKEN Center for Developmental Biology CDB125 in Kobe is focused on Life Cycle
Biology and Regenerative Medicine. Core programs include organogenesis, cellular environmentand response, mathematical developmental biology, and regenerative medicine.
Moving forward, CDB plans to concentrate the research activity into three themes:
Embryogenesis/Organogenesis, Regenerative Biology and Homeostasis & Aging
Figure 8.11: Left exterior of RIKEN CDB. Right, photography of Kobe125

http://www.cdb.riken.jp/en/

67

The research team headed by Professor Masayo Takahashi engages in basic science to translational
research on cell-based therapy for blinding eye diseases. In 2014, the clinical study in patients withage-related macular degeneration (AMD) using iPS cell- derived retinal epithelium sheets was theworld- first trial to use iPS cells in humans126 .

Figure 8.12: Left: iPS cells and RPE cell sheets; Right Prof. Masayo Takahashi

From 2017 a new clinical study conducted in Kobe and Osaka hospitals uses allogeneic iPS cells(unlike the autologous iPSCs transplanted in the previous clinical study in 2014). Allogenic cells areprepared in suspension. 5 patients have received them during the clinical trial in 2017.

The CDB is an active participant in the Kobe Innovation Cluster (see page 85)

In December 2017, the Kobe EyeCenter 127 (developed under National
Strategy Special zone) started operations
as a place to practice vision care in acontinuum from basic research, appliedresearch, clinical research, treatment, lowvision care, and employment support.
RIKEN

will

also

conduct

research

activities within Kobe Eye center.

The CDB is engaged in programs of cooperation with a number of universities in Japan and aroundthe world. This activity is based primarily on cooperation between individual researchers.

126
127

http://www.cdb.riken.jp/en/research/laboratory/takahashi.html/www.kobeeyecenter.jp/english/#greeting68European institutions with RIKEN CDB agreements may be a good bridging contact point for
Europeans willing to initiate industry-academia research collaborations with CDB

Center for Genomic Regulation; Institute for Research in Biomedicine; Universitat Pompeu Fabra (Barcelona, ES)
Max Planck Institute of Molecular Cell Biology and Genetics (Dresden, DE)
German Research Center for Environmental Health (Neuherberg, DE)
Freie Universitat (Berlin, DE)
VU University (Amsterdam, NL)

In September 2016, RIKEN CDB–Otsuka Pharmaceutical Collaboration Center (COCC)128
was launched to pursue projects in regenerative approaches related to neurodegenerative andkidney diseases. The COCC is located inside the CDB in Kobe, and headed by Hiroshi Hamada,director of the RIKEN CDB. The collaboration is initially launched for 5 years.

RIKEN CDB has active partnerships with multiple biotech and pharma companies, yetaccording to its 2016 Advisory Council report129 “clearly this could be raised to a higher level
through more outreach to companies to visit CDB and learn about the research there”.
Opportunities for collaborative research with Industry mentioned in the Advisory Council report
include increasing translational research by finding appropriate clinical partners to explore:

128
129

-

Kidney organoids in Nephrology,-

Oocyte chromosome anomalies in Reproductive Medicine-

Stem cells applications in Neurology, Dermatology and Respiratory Medicine

https://www.otsuka.co.jp/en/company/global-topics/2016/20160906_vol95.html
http://www.cdb.riken.jp/en/about/publicinformation/report/ac16.html

69

RIKEN Quantitative Biology Center (QBiC), in Osaka, aims to achieve “whole cell modeling”.
By combining techniques that can measure molecular dynamics, modeling cellular environments,and simulating molecular and genetic networks, scientists aim to predict and control the behavior of
the cell. Collaborations are handled via RIKEN Business development Office130

Computational Biology Research Core

Cell Dynamics Research Core

Computational Molecular Design

Cell Dynamics Observation

Biomolecular Function Simulation

Cell Signaling Dynamics

Biochemical Simulation

Comprehensive Bioimaging

Multiscale Biosystem Dynamics

Nano-Bio Probes

Drug Discovery Molecular Simulation Platform

Single Cell Mass Spectrometry

Developmental Morphogeometry

Developmental Dynamics
Polarity Regulation

Cell Design Research Core

Biomolecular Structure and Dynamics

Laboratory for Synthetic Biology

Single Cell Gene Dynamics

Laboratory for Cell-Free Protein Synthesis

Cell Field Structure

Laboratory for Integrated Biodevice

Reconstitutive Developmental Biology

Laboratory for Mouse Genetic Engineering

Integrative Omics

The RIKEN Center for Life Science Technologies (CLST) 131aims to promote research on
biomolecules and into life science technologies. Its focus is on 3 areas: Designing molecular
structures at the atomic level, manipulating molecular function at the cellular level and tracing
molecular dynamics at the whole-body level.
A Division of Structural and Synthetic Biology, a Division of Genomic Technologies, and theDivision of Bio-function Dynamics Imaging, work together. R&D programs are carried out incollaboration with companies, universities, and international consortia.

130
131

http://www.riken.jp/bdo/index.html
http://www.clst.riken.jp/en/70Facilities of the center include the largest collection of NMR devices in the world, based in
Yokohama campus; GeNAS is a technical service which aims to disseminate the genome-wide
analysis technologies developed by CLST. In Europe, CLST has close ties with the Swedish
Karolinska Institutet.

RIKEN PMI
The Preventive Medicine and Diagnosis Innovation Program from RIKEN (PMI)132
is an initiative which may also be interesting to European companies wishing to develop in Japan
medicinal products and devices for disease detection. Research groups taking part in the program areworking on the discovery of new biomarkers, the development of detection technology forclinical practice, and the development of diagnosis kits.
The program promotes collaborations within RIKEN and with universities, research institutes andhospitals both inside and outside Japan.
Key areas: Large-scale gene analysis
 Gene expression analysis
 The development of nucleic acid measuringmethods
 Medical applications
 Transcriptional regulation networks

In October 2016, the report from RIKEN cluster for industry partnership advisory council
recommended increasing its support and use of PMI, in the framework of promotinginternationalization. .

132

http://www.pmi.riken.jp/en71

RIKEN- Collaborations with Industry Organisation
RIKEN collaborates with industry in many different ways and is open to inquiries about potential
collaborations. Joint and sponsored laboratories, commissioned research, internships…
The Cluster for Industry Partnerships (CIP) promotes RIKEN’s joint research with industrial partners
by securing and managing intellectual property, handling administrative procedures for various
contracts, assisting venture businesses, and conducting outreach activities.

Within the Cluster, The RIKEN Innovation Center (RInC) is the office managing the Baton Zone
program for the transfer of RIKEN’s scientific achievements into commercial products throughpartnerships with private companies. Under the Baton Zone program, named after the track-and-field
relay, researchers from RIKEN and private companies work together on research projects
tackling specific technological challenges, proposed by private companies. Some collaboration
examples are given in figure below.

Figure 8.13: RIKEN Baton Zone program72

Another channel for interactions of companies with RIKEN is joint research with “Independent
Chief Scientist Laboratories”, which held by outstanding researchers, carry out special researchwith corporate funding.
One of these independent laboratories, which are noteworthy for the high number of collaborations
with industrial medicine developers, is Professor Yuichi Sugiyama lab, working on “Improving the
success rate for drug discovery based on the quantitative prediction of pharmacokinetics”.133
Sugiyama laboratory started in April 2012, with funds from 26 companies including Taisho
Pharmaceutical, Mitsubishi Tanabe Pharma, Kyorin Pharmaceutical, Shimadzu Corporation, etc.
It aims to establish Virtual clinical trials, an integrated support system for drug discovery andimprove the success rate significantly in drug discovery. In 2017 Dr. Sugiyama appeared in the
Clarivate list of Highly Cited Researchers134.
The Program for Drug Discovery and Medical Technology Platforms (DMP) is another anotherplatform leveraging RIKEN research centers and open for joint research with Industry.
Established in 2010, it is headed by Dr Tashio GOTO. Its business development office deals with
Industry requests.

Fields of focus:

RIKEN Industry Cooperation Headquarters

1.Small molecule drugs

Drug Discovery and Medical Technology Foundation Program

2.Monoclonal antibody drugs and vaccines

Address: 1-7-22 Suehirocho Tsurumi-ku, Yokohama-shi,

3.Cell-based drugs and regenerative medicine

Kanagawa

4.R&D for the construction of drug discovery andTel: 045-503-9153

medical technology platforms

pharma-support @ riken.jp

As an example, in March 2018, BrightPath Biotherapeutics, Co., Ltd. (a clinical stage
biopharmaceutical company) announced a collaborative research agreement with RIKEN regarding anatural killer T (NKT) pursued by the RIKEN Center for Integrative Medical Sciences, that aims at
technology development and clinical application of this novel allogeneic cancer immunotherapy
using NKT cells redifferentiated from induced pluripotent stem (iPS) cells (“iPS-NKT celltherapy”).This is a RIKEN-led project, on the Program for Drug Discovery and Medical Technology
Platforms. An investigator-initiated clinical trial targeting head and neck cancers is to start withinfiscal year 2019.

133
134

https://www.sugiyamalab-en.com/
http://www.riken.jp/outreach/applied/people/

73

RIKEN DMP is developing comprehensive technological platforms such as the Drug Discovery
Computational Chemistry Platform and the Biochemical and Cell-based Drug Discovery screening
platform.

Figure 8.14: Program for Drug Discovery and Medical Technology Platforms DMPRIKEN Support to Venture Companies

RIKEN Venture system enables researchers to put their own scientific achievements to commercial
use and disseminate the fruits of research at RIKEN as quickly as possible. The venture support
system by RIKEN had 20 companies certified as of November 2017, operating in diverse fields.
A company certified as RIKEN venture gets preferential treatment in licensing patent rights, use of
space, research equipment, and permission to engage in research as staff of RIKEN etc.

74

A legislation modification (expected to be approved by mid 2018), will grant RIKEN centers the samerights that Japanese Universities currently enjoy regarding investments in stock acquisition rights andventure funding. This change is expected to incentivize venture formation and support from RIKEN.
In the biotechnology field, some successful examples of companies that originated as RIKEN ventures
include the regenerative medicine companies Healios, Organ Technologies Inc.; companies basedon genetic technology DNAFORM, and antibody generation platforms (Chiome Bioscience).
Table: RIKEN Bioventures
Healios corporation135 originated as RIKEN venture in 2011. It was listed in
the Mothers Tokyo Stock Exchange market in 2015. It develops treatments basedon iPSC derived technology.
In 2013 in-licensed technology from CiRA (Kyoto University) and signed a joint
development agreement with Sumitomo Dainippon Pharma.
Healios does joint research with Yokohama City University on a platform
technology to induce organ bud growth (induce multiple types of tissue to form
physiologicallyfunctional

tissuewithvasculature

and

other

cellularinterconnections) in fields other than ophthalmology.

In February 2017, Healios received a Sakigake designation (see page 17) for
regenerative medicine products from PMDA, which should accelerate theapproval for its therapy for improving functional impairment caused by acutebrain infarction based on pluripotent progenitor cell derived from human(allogeneic) adult bone marrow.(partnering with Athersys US)
In March 2017 Helios formed a business alliance with Nikon on contract
manufacturing of cells / cell quality evaluation with image analysis etc.

135

https://www.healios.co.jp/en/

75Organ Technologies Inc 136 . works on innovation based on 3D organ
regeneration technology. The company is developing iPS technology
applications: Lacrimal glands and salivary glands (project with AMED);
Artificial skin mimicking human skin structure for medical & cosmetic research;
Hair follicle regeneration.
In December 2017 Organ Technologies formed a consortium based in open
innovation model with 18 companies (Kyocera, Yahoo, NEC, Mitsui, Aderans,
Shimadzu…). The objective of collaborative research being to develop andanalyze health indicators and disease markers from composition of hair, aiming
to establish hair analysis as a new noninvasive healthcare diagnostic system.
Chiome Bioscience137 was a certified RIKEN venture in 2005. In 2011 it waslisted in on the Mothers Tokyo Stock Exchange market.
Their drug discovery platform technology ADLib® system (Autonomously
Diversifying Library system) was originally developed through collaboration
with Genetic Dynamics Research Unit at RIKEN, and Saitama SME
development. With Tokyo headquarters, Chiome has R&D labs at LiC in
Kawasaki (see page 82).
Chiome performs joint research or contract service producing antibodies for new
clients (pharma) or for diagnostic and research purposes at academia or institutes
on fee-for-service scheme.
ADLib® is a monoclonal antibody generating system providing a diverse
array of complete antibodies in vitro, without using immunization.
ADLib® axCELL is a proprietary technology that Chiome Bioscience
successfully developed to obtain antigens from cells for use in the
ADLib® system.
Chiome has signed contracts with Chugai and Mitsubishi Tanabe.
In 2017 executed a license agreement with ADC Therapeutics (Switzerland) todevelop, manufacture, and commercialize LIV-1205, as Antibody Drug
Conjugate (ADC) for cancer treatment. LIV-1205 is a humanized monoclonal
antibody targeting cell surface antigen "DLK-1 (Delta-like 1 homolog)" of livercancer and other solid cancers.
ProBioGen AG (Germany) is Chiome’s partner for the Master cell banking and
GMP manufacturing.
136

http://www.organ-technol.co.jp/aboutus/

137

http://www.chiome.co.jp/english/76

It also signed a joint research contract in 2017 with Trans CHromosomics
Inc138. (a venture on chromosome engineering technology developed by Tottori
University), fostering drug discovery research on their fully human antibody
producing mice/rat complementary to Chiome’s existing antibody discovery
toolbox.
DNAFORM Inc139, certified as RIKEN venture in 1998, is a provider ofcomprehensive gene expression analysis technology and development & sale ofgenetic testing reagents.
In December 2016, DNAFORM signed a collaborative agreement with Russiancompany Eidos-medicine to develop a portable system to diagnose infections.
The company is based in Yokohama
RIKEN BIO Co. Ltd

RIKEN BIO Co Ltd was certified in September 2014 as RIKEN venture,
working on pre-symptomatic diagnosis and prophylactic treatment of Alzheimers
disease. With offices at RIKEN Brain Science Institute in Saitama, the venture
generated a knock in mouse model that start accumulating Aβ at 6 months andshow memory impairment at 18 months
AMBICION Co Ltd.140, established in October 2015, although not a Riken
venture, is included here because its technology originated from collaborative
agreements with RIKEN, on the development of cell-processing products using anovel natural killer T cells (NKT) ligand (RK), and carrying out non-clinical andclinical studies.
in April 2016 RIKEN and AMBICION jointly applied for a patent covering
efficient NKT cell activation. Ambicion is working on clinical programs withNKT cell-cancer targeted immunotherapies, within translational researchstrategic programs from AMED and Keio University.

The Full list of RIKEN venture companies can be consulted online141138

http://trans-chromo.wixsite.com/transchromosomics/r-d
https://www.dnaform.jp/en/about/140
http://www.ambicion.co.jp/en/technology/data.html
141
ww.riken.jp/en/outreach/ventures/
139

77

9.

Global Health R&D fund (GHIT): An alternative public-private partnership model

The Global Health R&D fund GHIT142 facilitates international product development partnerships
between Japanese and non-Japanese entities. The fund was initially launched in April 2013
between three key partners: Japan government, a group of leading Japanese pharmaceuticalcompanies, and the Bill & Melinda Gates Foundation. To date, GHIT has invested a total of US
115M in 68 global partnerships. For the next 5 years, US$200M are committed to the fundreplenishment.
GHIT focus is development of drugs, tests and vaccines for malaria, tuberculosis, HIV andneglected tropical diseases (NTDs). In an “open innovation” model of R&D, productdevelopment partnerships (PDPs) are created to facilitate international cooperation. The
Japanese counterparts are Universities/ Public Research Centers or private companies.
While the fund does not seek financial returns, decisions are data-driven and outcome-oriented.
Investments seek effective development of novel health technologies with the potential to savemillions of lives and drastically improve health and economic outcomes.
Some of the partnerships involve SMEs from outside Japan. For example, VLP Therapeutics,
an American start up, is contributing novel virus-like particle technology to a Dengue vaccine
project, where Japanese partners are the National Institute of Infectious Diseases (NIID) andInstitute of Tropical Medicine at Nagasaki University (ITM Nagasaki University).
Participation in a cooperative project funded by GHIT could be of high interest to European
SMEs, particularly for those biotech startups developing test devices or ancillary drug
development products and services. In addition to making an impact in Global Health R&D,
European SMEs participation in this type of funded partnership would be a way to startcollaborations with Japanese Academia and Japanese Industry and, potentially opening channels
to further collaborations in other projects.

142

www.ghitfund.org

78

10.

Industrial Clusters and Innovation Hubs

In 2001 Japan adopted the “Industrial Cluster Plan” to strengthen the capabilities of regional areas indeveloping new technologies and products. Grounded in the experience from other countries,
industrial clusters were defined primarily for Biotechnology, IT, environment and manufacturing,with the goal of strengthening national industry.143.
The biotechnology regional SMEs and start-up companies utilizing innovative research results or“seeds” obtained at local universities and research institutes would form clusters creating new
business, strengthening the existing ones, and thereby fostering the evolution of a concentration ofindustries in a wide area around a focal core of highly competitive industries. This strategy was
deployed in three phases144:-

A first term (2001-2005) where the national government had a central role in launching
projects;-

a second term (2006-2010) considered a development phase;-and a third term (2011-2020) were clusters should achieve financial independence andautonomous growth.

Japan External Trade Organisation (JETRO) has developed a mapping tool 145 that provides
information about regional specialised industrial clusters, including a map on Life Sciences.

In 2013 the EU-Japan Centre for Industrial Cooperation conducted a survey on Japanese clusters andpublished a report based on the replies collected from forty five Japanese entities. This information
was further updated in 2016146, through web based screening and analysis of the international
relations of the clusters. Twenty eight Japanese clusters were identified in the fields ofpharmaceuticals, biotechnology, healthcare, medical and welfare.

For their potential interest to European SMEs engaged in biotechnology healthcare applications,this report has selected some key Clusters and Innovation networks of Japan currently promoting
their activities and/or international collaborations, regardless of the public/private nature of theirfunders and sponsors.

143

JETRO Oct 2007 publication on Biotechnology
METI http://www.meti.go.jp/english/policy/sme_chiiki/industrial_cluster_en.html
145
https://www.jetro.go.jp/en/invest/region/icinfo/146
https://www.eubusinessinjapan.eu/library/publication/report-cluster-mapping-in-japan-2016
144

79

Table 10.1:Presented Industrial Clusters and Innovation Hubs

Area

Organisation nameAgreements signed with Europe

Tokyo

Life Science Innovation Network Japan

Eurobiomed (FR)

(LINK-J)

One Nucleus (UK)

Kanagawa

Lifescience

Innovation

Centre(LiC),

Kawasaki

Cell Therapy Catapult (UK), Oulu (Finland)
CVT Valorisation (FR)Scottish Development Intl. (UK)

Shonan Innovation Park (Takeda)
Osaka

Osaka BiobioXclusters plus（bioPmed / Bioindustry Park
（Italy）、Biocat（Spain）、BioM（Germany）、
Lyonbiopole（France )Flanders Bio (BE),

Kobe

Kobe

Biomedical

Innovation

Cluster(KBIC)

Flanders Bio (BE),Medicon Valley Alliance (DK, SE)

Procluster Kobe

Life Science Innovation Network Japan (LINK-J)TOKYO

The Life Science Innovation Network of Japan (LINK-J)147, based in Tokyo, is a platform aiming
for open innovation in the whole life science field, from medicine to science including engineeringor new technologies, such as ICT or artificial intelligence. LINK-J promotes interdisciplinary humanand technological exchange through industry-government-academia cooperation, and support to thecreation of new industries.
Operating since June 2016, LINK-J is a general incorporated association established by Mitsui
Fudosan (a leading company in the Japanese real estate industry, active in venture business) andvolunteers from life sciences academic circles. It counts over 180 members.
Prof. H. Okano, Keio University School of Medicine Dean, is the Chairman of the board.
Management advisory committee is integrated by experts from industry and academia.
Based in the Nihonbashi area of Tokyo, where a number of pharmaceutical companies like Takeda,
Astellas, Otsuka and many others have headquarters, the Nihonbashi Life Science Building is one of
the three facilities made available to LINK-J (with two other smaller buildings in close proximity).
147

www.link-j.org/en

80

Figure 10.1: LINK-J Tokyo situation map

Facilities include conference rooms hosting most LINK-J events. At the time of this research, it is
one of the venues most frequently used for presentations by Japanese ventures, as well as European
companies in missions to Japan.

Table 10.2: Multiple Japanese life science organisations have an office at LINK-J premises.
Japan Pharmaceutical Manufacturers Association

National University Corporation,

Japanese Society for Regenerative Medicine (JSRM)

Osaka University

FIRM (Forum for innovative regenerative medicine)

Kyoto University

Japanese Organisation for Medical Device Development

The University of Tokyo

Medical-Industry Cooperation Innovation Centre

Tohoku University

Japan CRO Association

Kyushu University

the Centre for Studies on Ageing Societies

Fukushima Translational Research

Clinical Research Education Centre Tohoku University

The University of California, San Diego

Hospital (CRIETO(US)

Shared office space with open desks is available, often rented by would-be venture companies orcompanies immediately after founding, promoting a concentration of smaller venture companies.
A start up acceleration program “Zentech dojo”, managed by INDEED Japan 148 , provides
educational programs and mentoring support. Link-J hosts partnering events and venture pitch
meetings to procure funds from angel investors and venture capitalists.

148

http://www.indee-jp.com/zentech/more-info.html

81International Cooperation
LINK-J has demonstrated its interest in expanding partnerships in Japan and overseas.
MOUs on business collaboration were first signed with the University of California, San Diego(UCSD) and BIOCOM (US) in May 2016.
On the European side, LINK-J has signed MOUs with two organisations: Eurobiomed (FR) in June
2017and One Nucleus (UK) in December 2017. Start- up companies’ presentations visits fromJapanese companies to Europe, and networking events have since been co-organised by theseorganisations with Link-J.

Life Innovation Centre (LiC) in Kawasaki, Kanagawa Prefecture
LiC Kanagawa149 is a private-public joint project, located in the city of Kawasaki (Kanagawa
prefecture), very close to Tokyo Haneda airport. It was launched in 2016, as a hub to promote theindustrialization of regenerative medicine. Working closely with national government, it benefits
from National Strategic Special Zone and International Strategic Zone policies.
LiC Kanagawa has an open lab 150 , cell production manufacturing facilities, and office space
available. As of October 2017, tenants at LiC Kanagawa (27 companies) included among others:
Cellular Dynamics International (acquired by Fujifilm, producing cardiomyocites from iPS)
BrightPath biotherapeutics (R&D on cancer immunotherapy, cancer vaccines in clinical trials)
Takara bio (CDMO and gene therapy development. Acquired Cellectis Sweden in 2014 )151
Cyberdyne Inc.152 (projects combining cellular therapies and robot exoskeletons. Initially a startup
from Tsukuba University)
PeptiDream Inc (see page 42)149

http://www.pref.kanagawa.jp/mlt/f531223/p1002234.html
http://www.lic-openlab.com/
151
http://www.takara-bio.com/release/?p=352
152
www.cyberdyne.jp
15082Tella pharma Inc153. Opened a manufacturing facility at LiC in March 2017, with extensive use ofrobots automation and IoT, manufacturing investigation product for their clinical trials with dendritic
cell vaccines.

Figure 10.2: Tella pharma Inc manufacturing facility at LiC

source: Tella website

Companies at LiC, have established the Regenerative medicine & Cell therapy Industrialization
Network of Kanagawa (RINK) 154 to build a value chain for cellular processing, cultivation,
evaluation, storage and transport processes. RINK organizes seminars, events, networking andinformation sharing between members, project planning and business matching support.
Within LiC, the "Kanagawa Clinical Research Strategy Research Center155" provides support on
clinical research of regenerative medicine products and innovative medicines. It has an access to
the Tohoku Medical Megabank organization, containing a large amount of genome cohort data.

LiC has signed MoUs with several European organizations such as Cell Therapy Catapult- UK,
Oulu-Finland and CVT Valorisation France. Scottish Development International has an office at LiC.

A recent example of overseas company partnering with a Japanese LiC counterpart is Agilis
Biotherapeutics, a US biotech company developing gene therapies which created a joint venturewith the Gene Therapy Research Institution (GTRI), a Japanese bioventure founded in 2014 basedon research by Prof. Muramatsu from Jichi Medical University, on adeno associated virus vector
mediated (AAV) gene therapy. In February 2017 the joint venture Agilis GTRI Japan156 R&D,
developing AAV vectors for gene therapies targeting the CNS, was established at LiC Kanagawa.
The company made use of METI subsidies to attract companies to Kanagawa prefecture, and was153

https://www.tella.jp/en/
http://rinkrink.jp/en/about/155
http://en.kccr.co.jp/
156
http://www.agilisbio.com/
154

83

supported by JETRO (see more details on this business case on Jetro website157)

European companies considering the possibility to establish a manufacturing or R&D base in Japan
should explore the advantages offered by International Strategic Zones like LiC Kanagawa.
An example is TC BioPharm Ltd., company from Scotland (UK), developing cancer
immunotherapies. In February 2018 158 it established its first overseas office in Japan at LiC
Kanagawa, to continue expansion of its Asian operations. The company worked with Scottish
Development International to find a suitable location in Japan. Last year the firm announced an$8million equity funding round, including its first significant investment from the major Japanesepharmaceutical company NIPRO Corporation (Osaka).

The Shonan Health Innovation Park, Kanagawa
The Shonan Health Innovation Park159 in Fujisawa, Kanagawa, was initiated by the Japanesepharmaceutical company Takeda in 2016. The park, envisioned as an open innovation project, istargeted to become “Japan’s first innovative ecosystem led by pharmaceutical companies bringing
together key players involved in health innovation from industry, government, and academia”,
according to Takeda speakers.
A catalyst for public-private
partnership, inviting human resources
and investment from all over theworld, Takeda is seeking fordiversified investors for new projects
starting in the park.
It offers access to research equipment
and workspaces. Immediate research
Source: Takeda website

access without initial investment.

Over 50 R&D partnerships have been formed in two years, with future aspirations voiced asreaching a scale of thousands of researchers and stakeholders in the Innovation Park.

157

https://www.jetro.go.jp/en/invest/success_stories/agilis.html
https://www.insider.co.uk/news/tc-biopharm-launches-new-office-12023842
159
https://www.shonan-health-innovation-park.com/en
15884

T-CiRA, a research unit founded in collaboration with Kyoto University’s Center for iPS Cell
Research and Application (CiRA), is a prime example.(see page 48)
New venture companies are joining the park, for example K Pharma160 (a bioventure spinning out
from Keio University doing drug discovery with iPS cells) and Noile-Immune Biotech 161(exclusive licensee of the platform technology for next generation CAR-T cell therapy developed by
Yamaguchi University).
Other companies in the Shonan Park are developing drugs from Takeda’s divested pipeline:
SCOHIA PHARMA Inc.162 with clinical stage programs in diabetes, and diabetic nephropathy
hypertension; Chordia therapeutics163 developing new therapeutic agents for cancer treatment (seepage 54) and FIMECS, Inc 164 . established in January 2018 to develop protein degradation
therapeutics for cancer and other difficult to treat diseases.
MIT Startup Exchange Showcase Japan165 was held at the Shonan Health Innovation Park in
October 2017.

Kobe Foundation for Biomedical Research and Innovation
At the Foundation for Biomedical Research and Innovation (BRI)166, Pro-Cluster Kobe167 is theorganisation supporting companies from the Kobe biomedical research cluster (KBIC)168, andfostering collaborations with foreign life science clusters.
International agreements have been signed with the German cluster Life Science Nord (from theNorthern German States of Hamburg and Schleswig-Holstein); with the Belgian Flanders Bio andMedicon Valley Alliance (from Denmark & Sweden). Agreements with China Medical City
(CMC) in Thaizou (China), are also in place.
KBIC, one of the largest biomedical clusters in Japan, celebrated its 20th anniversary in 2018.
It includes research institutes (RIKEN Centre for Developmental Biology (CDB) (see page 66),
Translational Research Informatics Centre (TRI), Advanced Institute for Computational Sciences160

http://kpharma.co.jp/information/
https://www.noile-immune.com/english/162
https://www.scohia.com/eng/163
http://www.chordiatherapeutics.com/eng/update/pdf/20171122_EN.pdf
164
http://www.fimecs.com/eng
165
https://ilp.mit.edu/conference.jsp?confid=180&tabname=overview
166
http://www.ibri-kobe.org/
167
http://www.ibri-kobe.org/english/cluster/168
http://www.kobe-lsc.jp/en/16185

(AICS) K Computer...), highly specialized hospitals, and multiple medical companies and groups,
related to a variety of themes including treatment, diagnosis, prevention, caregiving, welfare, etc., inpharmaceuticals, medical equipment, regenerative medicine, and other fields.

On regenerative medical research, contract manufacturing and a cell processing centre are alsoavailable at the Foundation for Biomedical Research and Innovation. (IBRI laboratory)169, which isopen to collaborative research with enterprises and universities. Examples of regenerative research
projects include: Repair of cornea with autologous mucosal sheet, treatment of unhealed fractureswith mobilised CD34+cells, or Regeneration of tympanum membrane by bFGF/ sponge.
Acceleration programs such as Kobe x BRAVE for entrepreneurs170 in life science/health/medical
device take place at KBIC, under sponsorship from NEDO, Kobe city, Pharmaceutical/Medical
device companies (Bayer, Merck, BMS, Ikeda Scientific Co. Ltd…) and Venture Capital Funds(Beyond Next Ventures).

Figure 10.3: Kobe BRAVE Program

169
170

https://www.fbri-kobe.org/kbic/
https://kobexbrave.tech86

Osaka Bio
Osaka Bio Headquarters171, is an initiative for increasing Osaka and Kansai region international
competitiveness in the life science field, promoting activities at large-scale overseas trade fairs
working on creating a foundation for international exchange programs with overseas life scienceclusters. It support the overseas business exchanges between the companies based in Osaka andKansai. Universities and research institutions are concentrated mainly in the northern part of Osaka,and many pharmaceutical companies have their headquarters in that area. Major Institutions include:-

The Saito life Science Park172, established in 2004 as a major base for R&D, including
incubation facilities. Very active in organising seminars dealing with various themes related to
the field of life science, offering an opportunity for information gathering, networking andexchange.

-

The Northen Osaka Health and Biomedical innovation town (KENTO), a cluster around the
National Cerebral and Cardiovascular Centre.

-

The National Institutes of Biomedical Innovation Health and Nutrition (NIBIOHN)-

Universities and Research institutes previously mentioned in this report, such as Osaka
Universities, the Immunology Frontier Research Center (IFReC) (see page 58), and RIKEN
Quantitative Biology Center (QBiC) (see page 70).

Osaka has stablished numerous MoU with European organisations and life science clusters:
bioXclusters plus（bioPmed / Bioindustry Park（Italy）、Biocat（Spain）、BioM（Germany）、
Lyonbiopole（France) and FlandersBio.

11.

Academic Societies and Associations

Japan Bioindustry Association (JBA)173
JBA in cooperation with organizations supporting venture companies of each region in Japan.
maintains an online directory of Japan bioventure companies174.
By broadly disseminating this information, JBA aims to promote the creation of business allianceopportunities in Japan and abroad, and contribute to their activity.

171

https://osaka-bio.jp
https://osaka-bio.jp/support/seminar/
173
https://www.jba.or.jp/en/about/174
https://area34.smp.ne.jp/area/table/5697/FDN_H3/M?S=lbsfn2mbnak
172

87

In March 2018, the bioventures directory included 114 companies: 60 hits corresponding tocompanies performing “pharmaceutical/drug discovery” and 53 hits for the activities “Drugdiscovery support/Contract service”

The Forum for Innovative Regenerative Medicine (FIRM)
FIRM, the trade association in Japan regenerative
medicine field, was established in 2011, and today has
more than 230 member entities.

Since 2014, FIRM provides assistance to overseas
companies, in cooperation with the Japan External
Trade Organisation (JETRO), providing information
relating to RMPs and introducing member companies
that would make appropriate partners. RMIT is a task
force within FIRM, working as contact on questions
FIRM organizes “crossroads meetings”

about industrialization of regenerative medicine.

to facilitate networking to those seeking

The booklet edited by FIRM, and online listing175 ofpartners and licensees in Japan. Several

member companies are very useful to get an idea ofcompanies from Europe have attended

Japanese RM companies and activities at a glance.

these meetings in 2017

FIRM signed MoU with Catapult, UK in 2017.

The Japanese Society for Regenerative Medicine JSRM
Established in 2001, JSRM176 is the largest society for regenerative medicine in the world, withapprox. 6000 members involved in research in basic medicine/dentistry, clinical medicine, tissue
engineering, cell biology, as well as bioethics, regulatory science, law and medical economics.
After 2016, JSRM acquired funds from the Agency for Medical Research and Development(AMED), and has been supporting clinical research, development of human resources, andcoordination between academia and industry. One of its latest projects is the National Regenerative
Medicine Database (NRMD), an important contribution to the field of acquisition of real world
evidence from all cases of regenerative medicine and cell therapies.
In February 2018, JSRM signed a MoU with Catapult (UK).

175
176

https://firm.or.jp/en/introduce
www.jsrm.jp

88

JSRM coorganises the TERMIS World congress (Tissue Engineering and Regenerative Medicine
International Society) congress which is held every three years, and brings together researchers,scientists, clinicians, and students from academia and industry to discuss critical developments. The
5th TERMIS world congress will take place in September 2018, in Kyoto.

Japan Society of Gene and Cell Therapy
Established in 1995 , the Japanese Society of Gene and Cell therapy177 JSGT coorganises
symposia178 with The Institute of Medical Science, The University of Tokyo (IMSUT) (see pg 38)

Table 11.1: Other Japanese Academic Societies of interest to biotech companies in Europe

Japanese Society for Bacteriology

http://jsbac.org/

Japanese Society for Chemical Biology

http://www.jscb.jp/index_e.html

Japanese Society of Epigenetics

http://square.umin.ac.jp/jse2017/

Japanese Society for Immunology

http://www.jsi-men-eki.org/english/

The Biophysical Society of Japan

http://www.biophys.jp/index-e.html

The Japanese Society for Bioinformatics

https://www.jsbi.org/en/

Protein Science Society of Japan

http://www.pssj.jp/en/

Japan Human Proteome Organisation

https://www.jhupo.org/english/

Japan Society for Cell Biology

http://www.jscb.gr.jp/en/

The Japan Society of Human Genetics

http://jshg.jp/e/

The Japanese Society for Genome Editing

http://jsgedit.jp/en

The RNA Society of Japan

https://www.rnaj.org/en/

The Molecular Biology Society of Japan

http://www.mbsj.jp/en/index.html

177
178

http://www.jsgt.jp/
http://www.jsgt.jp/ANNOUNCE/5cgct_program.pdf

89

12.

Tradefairs and Organisations

The most common way of meeting new potential partners in Japan is via networking in tradefairs,
congresses and conferences.
BioJapan179, the main exhibitions taking place in Japan on the life science biotech sector, is apartnering event, gathering over 1500 participants from 35 countries, including more than 800
exhibitors. With a very large representation of Japanese companies participating to the event, it is avery effective event to meet potential partners. Next edition is scheduled to take place 10-12
October 2018, in Yokohama.
Cluster support Missions on Biotechnogies in Japan180 are organised by the EU-Japan Centre forIndustrial Cooperation. The mission is a three day event structured in two parts:-

participation to a B2B matching event coorganised by European Enterprise Network (EEN)
and the Senri Life science Foundation of the Osaka prefectural government-

participation to BioJapan, with possibility to display company information and hold meetings
at the exhibition booth, with support from professional interpretation services

The EU-Japan Centre for Industrial Cooperation 181 is a unique joint venture between theEuropean Commission and the Japanese government. It aims to promote all forms of industrial, tradeand investment cooperation between EU and Japanese companies, to improve their competitivenessby facilitating exchanges of experience and know- how. The Centre is based in Tokyo with a branch
office in Brussels.

13.

Recommendations and Conclusion

European biotech companies with a successful entry on the Japanese market, frequently report that
establishing an agreements with a Japanese counterpart can be a lengthy process. It may require
longer timelines and more formal communication than in other regions of the world, leading toparticularly solid and fruitful partnerships.

International tradefairs and scientific congresses are an excellent environment for EU SMEs toinitiate discussions with potential Japanese partners. Participation to several editions of BioJapan, or
179

https://www.ics-expo.jp/biojapan/en/
https://www.eu-japan.eu/events/biotech-cluster-sme-mission
181
https://www.eu-japan.eu/
18090persistently meeting both at Biojapan and then again at BioEurope, are strategies mentioned by some
SMEs as key to the establishment of agreements.

EU SMEs can obtain very useful support from organisations like the bioclusters, local national andregional chambers of commerce in Japan, and the EU-Japan Centre for Industrial Cooperation.

Matching partnership events, offered by several of the organisations mentioned in this report, such as
LINK-J, Japanese regional clusters like Osaka Bio, or the regenerative medicine FIRM events, areparticularly tailored to benefit EU SMEs networking needs.

The possibility of working with a local intermediary, Japanese agency or broker company is also
something to be considered.

The acquisitions of EU biotech companies by Japanese pharma, such as the take over ofBelgian/Spanish TiGenix by Takeda in 2018, or the acquisition of Danish CMC Biologics by Asahi
Kasei are examples showing that Japanese companies are more than ready to absorbe emerging
technologies from Europe.

While major pharma groups make obvious targets, when it comes to finding partners in Japan,
joining forces with small local players could also be a valuable strategy.
The establishment of cooperation between European SMEs and Japanese bioventures may be a
way to overcome some of the obstacles that young biotech companies are facing for growth in bothterritories:-

Japanese bioventures tend to be oriented towards their domestic market. Focusing on forming
alliances in Japan, they may be ignoring overseas opportunities which could also be very
profitable to them. Language barriers are often an additional difficulty in their dealing withoverseas companies.

-

European SMEs usually lack the specific knowledge of local academic and industrial landscapein Japan, which could potentially enlarge their base of Japanese partners/clients.

-

It can be very difficult for EU SMEs to offer the level of service required by Japanese clients
without at a local contact.

In this context, European SMEs considering internationalization in the Japanese market, may finduseful to explore alternative partnership and collaboration schemes with young Japanese bioventurecompanies, such as those presented in this report, which could potentially enable them to complete
the services offered in both territories.

91

European biotech SMEs considering the possibility to establish a manufacturing, or an R&D basein Japan should explore the advantages offered by International Strategic Zones (like LiC
Kanagawa, or Kyoto, for example), and JETRO can provide valuable support on the identification of
applicable incentive measures to foreign investment.

Annexes

Annex 1: Japanese bioventures exhibiting at Japan Healthcare Venture Summit 2017DD

Drug and Drug Discovery

DS

Drug discovery Support, Research equipment/Contract services

RM

Regenerative medicine products

VC

Venture Capital FundAMBICION Co., Ltd.

RM

Amelieff Co., Ltd.

DS

Axcelead Drug Discovery Partners, Inc.

DS

Beyond Next Ventures, Inc.

VC

Biomimetics Sympathies, Inc.

DS

BioSeren Tach, Inc.

DD

Brightpath Biotherapeutics Co. Ltd.

DDBTB Japan, Inc.

DS

CellFiber Co. Ltd.

DSCHIOME Bioscience, Inc.

DD

DS

Epsilon Molecular Engineering, Inc.

DD

DS

Epigeneron LLC

DS

GeneCare Research Institute Co. Ltd

DD

Ginreilab Inc.

DSGORYO chemical Inc.

DD

Hamamatsu University School of Medicine

DD

Himuka AM Pharm. Corp.

DS

Institute of Microbial ChemistryDS

Kyoto prefectural University of Medicine/ Minimum Lab

DS

MC Data Inc.

DS

RM

DS

RM

92

MEDINET Co. Ltd

DS

MedVenture Partners, Inc.

VC

MeSCue-Janusys Inc.

RM

MIRTeL Co., Ltd.

DS

Momotaro-Gene Inc.

DD

NanoCarrier Co., Ltd.

DDNANOSION Co., Ltd.

DD

Nobelpharma Co. Ltd

DD

Noile-Immune Biotech, Inc.

DD

Novumcella Inc.

RM

Osaka City University

DS

Osaka University Venture Capital (OUVC)VC

PrevenTec Inc.

DS

ReqMed Company, Ltd.

DS

Rhelixa Inc.

DD

Saitama University

DS

SEEDSUPPLY, Inc.

DSSENTAN Pharma Inc.

DD

Shinjuku healthcare incubation park (SHIP)

DS

Shonan Health Innovation Park

DS

Sumitomo Dainippon Pharma PRISM partnerships

DD

TAGCyx Biotechnologies, Inc.

DD

Taiho Pharmaceutical Co., Ltd. / Taiho Ventures, LLCDD

TFK Co. Ltd.

DDThe University of Tokyo Edge Capital (UTEC)VCTWO CELLS Company, Ltd.

RM

Unlog K.K.

DS

VC

RM

VC

Medical Devices excluded from original list

93

Annex 2 List of National Universities182

Hokkaido and Tohoku 14

Hokkaido University
Hokkaido University of Education
Muroran Institute of Technology
Otaru University of Commerce
Obihiro University of Agriculture and Veterinary Medicine
Asahikawa Medical University
Kitami Institute of Technology
Hirosaki University
Iwate University
Tohoku University
Miyagi University of Education
Akita University
Yamagata University
Fukushima University

Kanto and Kohinetsu 26


182

Ibaraki University
University of Tsukuba

http://www.mext.go.jp/en/about/relatedsites/title01/detail01/sdetail01/1375122.htm

94



Tsukuba University of Technology



Utsunomiya University

Gunma University

Saitama University

Chiba University



The University of Tokyo



Tokyo Medical and Dental University

Tokyo University of Foreign Studies

Tokyo Gakugei University

Tokyo University of Agriculture and Technology

Tokyo University of the ArtsTokyo Institute of Technology

Tokyo University of Marine Science and Technology

Ochanomizu University



The University of Electro-Communications



Hitotsubashi University

Yokohama National University

National Graduate Institute for Policy Studies



The Graduate University for Advanced Studies

Niigata University

Nagaoka University of Technology

Joetsu University of Education



University of Yamanashi

Shinshu University

Tokai, Hokuriku andUniversity of Toyama

Kinki Area 25Kanazawa University

University of FukuiGifu University



Shizuoka University

Hamamatsu University School of Medicine

Nagoya University

Aichi University of Education

Nagoya Institute of Technology

Toyohashi University of Technology



Mie University

Shiga University

95



Shiga University of Medical ScienceKyoto University



Kyoto University of Education



Kyoto Institute of TechnologyOsaka UniversityOsaka Kyoiku University

Hyogo University of Teacher Education



Kobe UniversityNara University of EducationNara Women's University



Wakayama University

Japan Advanced Institute of Science and Technology

Nara Institute of Science and Technology

Chugoku and Shikoku 10

Tottori University
Shimane University
Okayama University
Hiroshima University
Yamaguchi University
Tokushima University
Naruto University of Education
Kagawa University
Ehime University
Kochi University

Kyushu and Okinawa 11

Kyushu University



Kyushu Institute of Technology

Saga University



Nagasaki University

Kumamoto UniversityOita University

University of Teacher Education Fukuoka



University of MiyazakiKagoshima University

University of the Ryukyus

96