1. Bridging Science to Business in Biotechnology
Setsuko Hashimoto, Ph.D.
President and CEO
CellSeed Inc.

2. Agenda Market Potential of Regenerative Medicine
“Cell Sheet Engineering”
Corporate Overview
Development of Regenerative Medicine
Epithelial cell sheet for esophageal regeneration
Regenerated cartilage cell sheet
Intelligent Cell Cultureware
Bridging Science to Business in Biotechnology
“Dual receptor model”

3. “Cell Sheet Engineering” as Regenerative Medicine Platform Technology
Cell sheet engineering is the platform technology to continuously create regenerative medicine
1900～　　　　1980～　　　　　 2010~　　　
Chemical
compound
medicine
Bio-engineered
medicine
Gene medicine
Cell medicine
Tissue
medicine
so called “medicine” prescribed by hospital or pharmacy
artificially formed by chemical synthesis
genetically engineered proteins
typically, anti-body medicine
“genes” are used as medicine
“live human cells” are used as medicine（i.e. cancer immunotherapy）
“live human tissues” are used as treatment tools　　　　　　　　　　　　　（＝regenerative medicine）
As you know, So far major medicine is low molecular drugs synthesized by organic chemistry, and Biologics and gene therapy has been developed based on molecular biology. These medicines are composed of materials. Recently Cell, a minimal component of life, are found to be potential for future therapy. As next generation products, we would like to propose Cell Sheet Medicine. We utilize somatic stem cell to make functional tissues for regenerative medicine based on Cell Sheet Engineering..
This Cell Sheet engineering was established by Prof. Okano in Tokyo Womens’ Medical University.
Regenerative Medicine Regulation
in force on
The Act of Ensuring Safety of Regenerative Medicine
Revised Pharmaceutical affairs law 2

4. Future National Market Expectation
Future Market Expectation of Related Industries of RM
Size of related industries of regenerative medicine in 2050 is approximately 13billion USD (domestic market), 150 billion USD (global market), which also promises that future economic effects.
Future National Market Expectation
2020
950mil USD
2030
5.5 bln USD
2050
13 bln USD
2012
170mil USD
services
consumable supplies
devices
(Billion USD) 15 10 5
2012　　2020　　 　
160
140
120
100 80 60 40 20
Future Global Market Expectation
2020
11bln USD
2030
52bln USD
2050
150bln USD
2012
2.4 bln USD
Europe
Japan
Others
(developing countries etc.)
(Billion USD)
2012　　　　2020　　 　 　　2040　　
And in this report, they have estimated the market volume of the related industry, like cell-processing facilities and mediums etc.
As you can see, supporting industry market will also grow and will get to about 150 billion USD in 2050.
Please look at the left hand side graph, the market size of consumables and related services will become several times larger than the market of devices and machines.
RM market is really promising.
U.S.
Source: METI Report

5. “Accelerated Authorization” Introduced to Japanese Regenerative Medicine Regulation
Until 2013
Safety confirmed
Efficacy confirmed
Pilot
clinical
research
Clinical trial
Regulatory
Authorization
Launch
Provisional
Authorization
Safety confirmed
Efficacy presumed
From 2014
Re-application within due
Pilot
clinical
research
Clinical
trial
Launch
based on
Full
Based on
Source: Lit Search, “Regenerative Medicine” Vol. 12 No.3 (The Japanese Society for Regenerative Medicine) 4

6. Corporate overview Establishment May, 2001
Basic technology Cell-sheet engineering using temperature-responsive polymers
Business • Cell Sheet Regenerative Medicine
• Intelligent cell cultureware
Head office Katsura Bldg., 4F, 3-61 Haramachi, Shinjuku-ku, Tokyo
Directors President and CEO　 Setsuko Hashimoto, Ph.D
Executive Director Katsumi Katayama
Executive Director Hiroshi Yoshida
Executive Director Eiji Takagi
Auditor（External）　 Teruo Okano, Ph.D
Auditor　 Ichiro Kobayashi
Auditor（External） 　 Noriko Sawai
Auditor（External） 　 Toshio Yamaguchi
Fiscal year January - December
No. of employees 30 (as of April 30, 2015）
Publicly listed on JASDAQ (in 2010)

7. Core competence: Cell sheet engineering
Temperature-responsive polymers allow recovery of intact cells in a sheet form. Developed by Prof. Teruo Okano, Tokyo Women’s Medical University, Japan
Intelligent surface of the cultureware
37℃　hydrophobic　 ⇔　　　20℃　hydrophilic

8. (Used in conventional regenerative medicine and cell therapy)
Advantages of Cell Sheet: Autonomously Functioning Bioengineered Tissue
Cell Sheet
Isolated cells
(Used in conventional regenerative medicine and cell therapy)
1. Functioning as a basic unit of
biological tissue/organ
Low safety risk
Immediately becomes part of the body
● Isolated cells not functioning as tissue
2. Extra-cellular matrix preserved
Graft possible with no sutures
Remains and continues to produce factors that aid tissue regeneration over the long term
● Lost “extra-cellular matrix”
3. Multiple layering possible
= 3D tissues/organs construction possible
● Very difficult to construct 3D tissues/organs

9. Number of therapies in different organs are developed
Cell Sheet Engineering
Number of therapies in different organs are developed
Esophageal duct
Cornea
Heart
Ear
Knee Cartilage
Pancreas
Liver
Lung
Peridontal ligament

10. Medium-term management plan（2015～2017）
Aiming for bringing new therapies globally through development of regenerative products
Commercialize
regenerative medicine
soonest possible
Japan as the hub
for regenerative
medicine
Increase profit
promoting
development of
intelligent cell cultureware
Global
business
development

11. Cell Sheet Regenerative Medicine Pipelines
Starting clinical trial
sponsored by CellSeed
Epithelial cell sheet for esophageal regeneration
Regenerated cartilage sheet
Promote our own development
Cell Sheet for periodontal tissue generation sheet
Explore possibility for joint development
Epithelial cell sheet for corneal regeneration
Regenerated cardiac patch
Explore cooperation with partner(s)
Prioritized business
for 2015 角膜

12. Cell Sheet Regenerative Medicine Epithelial cell-sheet for esophageal regeneration
Treatment method to prevent esophageal stricture after removal of esophageal epithelial cancer developed by Tokyo Women’s Medical University
Transplant the cultured autologous oral mucosal epithelial cell sheet in the intelligent cultureware on the ulceration after endoscopic surgery
CellSeed develops devices for transplanting cell sheets

13. Japan：Clinical trial under consideration to obtain marketing approval
Favorable outcomes are observed in reconstruction of esophageal epithelium after removing cancer 　　　
Conducted 3 pilot clinical researches at 3 hospitals in 2 countries（Investigator initiated type with 30 patients）
Japan：　 Tokyo Women’s Medical University, etc.
Europe：　Karolinska University Hospital
Japan：Clinical trial under consideration to obtain marketing approval 　
Europe：Clinical trial in Sweden under consideration
Develop devices for transplanting cell sheet

14. Cell sheet Regenerative Medicine
Organizational idea of clinical trial for epithelial cell sheet for esophageal regeneration
Research outcome
at CSTEC
CSTEC=Cell Sheet Tissue Engineering Center,
Tokyo Women’s Medical University
Development
Japan
Europe
CellSeed
Contract
Contract
CellSeed Sweden AB
CRO
CRO

15. Cell sheet regenerative medicine for Regenerated cartilage sheet
Prof. Masato Sato, MD, Ph.D.,
Dept. of Orthopedic Surgery, Tokai University
Organically conjunct “cell sheet” consisting of intact cells
Preserved extra-cellular matrix
Multiple layers
Preventing proteoglycan escape
Protection against catabolic factors
Source of growth factors
Transplantation
3D tissues/organs construction
Recovery and
regenerate cartilage
Multiple layered cell sheets

16. Cell sheet regenerative medicine for Regenerated cartilage sheet
Prof. Masato Sato, MD, Ph.D.,
Dept. of Orthopedic Surgery, Tokai University
2011. August Approved by the 65th Science and Technology working group meeting
in the Health Science Committee of MHLW
2011. October Minister’s statement was released
（Minister of Health, Labour and Welfare, health Policy Bureau No ）
2011. November First patient in the pilot clinical research started　　　
2014. November Completed transplantation for 8 patients, and evaluated all after one year and confirmed good outcome on the postoperative courses 　　
Completed pilot clinical research with autologous cells at Orthopedic Tokai University
Next step
Pilot clinical research with allogenic cells aiming for joint treatment
（Minister’s statement was released on ）
Plan to start a clinical trial with autologous cells sheets in 2016
Indication：　cartilage defect, knee osteoarthritis

17. Establishment of our own Cell Processing Center
Considering to establish a facility for producing cell sheet pipelines
GCTP compliant facility is required
Images

18. Intelligent cell cultureware
Increase profit by promoting new product development
Cultureware for clinical applications
Devices for transplanting cell sheets
New applications for cultureware

19. CellSeed business based on cell sheet engineering
Covering all value chain for regenerative medicine business
Culture cells
Culture cell sheet
Treatment with
regenerative medicine
Body cells・Stem cells
iPS cells
Temperature-responsive
cell culatureware
Intelligence
culatureware
Production ＆ delivery
of cell sheet
再生医療はその標的によって、様々なアプローチがある。
1970年代から８０年代にかけて、多くの増殖因子や栄養因子,分化誘導因子が発見され、９０年代にその機構が明らかになり始め、
それらの因子を利用する段階になって、再生医療用のバイオ医薬の開発が進みつつあります。また、それらの因子関連の遺伝子の利用も始っています。さらに、組織由来の幹細胞、体性幹細胞や胚性幹細胞を利用した細胞医薬の臨床試験が始まっています。さらに、細胞医薬からTissue Engineeringを用いて組織を構築し、組織医薬、さらに臓器の構築が始まっています。
Regenerative
medicine 18

20. Business Model of CellSeed: - from bench to bedside-
Hospitals
Research collaborataion
Patients
Product development
Approval
Manufacturing
Universities
Source of innovation
products
therapy
seeds
fee
fee
Business collaboration
Other companies 19

21. My contacts with CellSeed
Organized events to celebrate 200 anniversary of Karolinska Institutet as a member of Embassy of Sweden in Tokyo in 2010.
Coordinated research collaboration between TWIns and Karolinska Institutet for esophageal cancer treatment.
Oct at TWIns in Tokyo
Nov at Karolinska Institutet in Stockholm

22. Signal transduction pathway in the cell
gene
DNA
nuclear
cytosol
receptors
mRNA
protein
Responses to the signals
Signal transduction
Gene expression

23. Dual Receptor Model
Business receptor
Science domain knowledge
Science receptor
Business domain knowledge
Business information
Upon receipt of information, a signal is transduced
Science information

24. Bridging Science to Business
Gather business information (use network)
Find the right people to test the idea on (use network)
Develop commercialization strategy
Develop the right marketing and sales channels (use the network)
Understand science information from the inventor
Get response on product/concept from customer =scientist)
Turn science into valuable benefits

25. Dynamic knowledge networking model
time
Knowledge Networker
Information
Activation of network
Science Business
　　　　　　　　Domains
Inacitve network 24

26. Bridging science to business in biotechnology - A science-business networker-
Need more science-business networkers!
Need to facilitate the training and education of science-business networkers
Provide combined science and business training to those who have a genuine interest and talent

27. Thank you for your attention!
Contact : Setsuko Hashimoto, CEO, CellSeed Inc.
This presentation material has been prepared by CellSeed Inc. for information purposes only. Copyright 2015 CellSeed Inc. All rights reserved.
The information and opinions contained in this material have been obtained from sources believed to be reliable, but no representations or warranties, express or implied, are made that such information is accurate or complete and no responsibility or liability can be accepted by CellSeed for errors or omissions or for any losses arising from the use of this material.
This information also contains forward-looking statements concerned with plans, strategies and forecasts on future business performance of CellSeed group. CellSeed wishes to alert readers that such statements involve risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, reliance on collaborators, need for additional capital, uncertainty of clinical trial results or regulatory approvals or clearances, maintenance of our intellectual property rights, changes in the business and economic environment and other factors. Actual results may differ materially from the results anticipated in these forward-looking statements. CellSeed disclaims any duty to update information provided herein. No part of this material shall be reproduced or redistributed in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior written permission of CellSeed Inc.