Ken-ichi AraiProfessor Emeritus, University of Tokyo Asia-Pacific IMBN (Founding President)

SBI Biotech Ltd./Ginkgo Biomedical Research Institute (President & CEO)

September 13, 2010

Building East Asia Life Science and Biotechnology Network of Japan, Taiwan, China and Korea -Genomic and Personalized Medicine in Health and Disease-

1. Bilateral: Japan and Taiwan(RIKEN, AIST, OIST, Academia Sinica, ITRI, university)

2. Via North America(i.e. university and research centers of US etc)

3. Via Network of Asia(A-IMBN, A-IMBN Research, CSH Asia, ICGEB, IVI, East Asia Symposia, Institutional Network etc)

4. Via Biotech Ventures & Pharmaceutical Industry(need to be developed)

Life science researchers of Japan and Taiwan collaborate in many ways

In 21st century, life science grew rapidly in Asia

MalaysiaSingapore

Indonesia

China

Australia

EMBO/EMBL

Israel

New Zealand

Korea

Governments Industry

Creation of New Knowledgeand New Industry

Philippine

Thailand

Scientists

FDA NIH CDC

Asia Pacific Life Science Highway Landscape in 1980

Europe North America

Cold Spring HarborLaboratory

India

Japan

Vietnam

New Zealand

India

Malaysia SingaporeIndonesia

ChinaAustralia

EMBO/EMBL

IUBMBICGEBUNESCO

Israel

New Zealand

Korea

Governments Industry

Asia Pacific Life Science Highway

Creation of New Knowledge and Innovative Industry

Philippine

Thailand

Scientists

FDA NIH CDC

Europe North America

Cold Spring HarborLaboratory

Pakistan

A-IMBN ResearchNature AP

Japan

A-IMBN/eIMBL& Research Network

CSH AsiaVietnam

Taiwan

Asia Pacific Life Science Highway 2010

In 21st century, life science grew rapidly in Asia

Okinawa OIST

Houston MDACC

Singapore BioPolis

ICGEB

TaiwanACADEMIA SINICANTU, NHRI

StanfordSeoul Bio-Max・IVI Shanghai SIBS/IBCB

A-IMBN/eIMBL/EMBO/ICGEB

MalaysiaBioNexusAMDI

VietnamHanoiHCM BTC New Dehli

electronicInternationalMolecularBiologyLaboratory

ThailandBIOTEC

Questions on Cell and Body in Health and Disease

1. Control of Cell NumberProliferation vs Growth ArrestSurvival vs Death

2. Control of Cell FunctionDifferentiationPhysiology

3. Control of Cell FateStem Cells & Development

4. Organs and Brain FunctionBrain Science

5. Diagnosis, Therapy, PreventionInfectious DiseaseAutoimmune Disease & Cancer

In 1890s Passive Immunity (Emil Von Behring, Shibasaburo Kitasato)Serum therapy for tetanus, antitoxins for diphtheria and anthrax

In 1910s Silver Bullet (Paul Ehrllich)Salvarsan, NeosaravarsanIn

In 1920s Antibiotics (Alexander Fleming, Howard Walter Florey)penicillin

P. Ehrllich S. Hata

Biotechnology of Infectious Diseases-Immunological and Chemical Approach-

European roots

Penicillin

Basis of Drug Development in early 20th centuryOrganic Chemistry

European roots

In 1970s Acquired Immunity & B cells Monoclonal Antibody

In 1980s Acquired Immunity & T cellsCytokines and Cytokine Receptorsimmunosuppressive drugs (Cyclosporin, Tacrolimus)

In 1990s Innate Immunity & DC cellsmDC, pDC, TLRs

In 2000s Vaccines for Viral Diseases & Cancer

Biotechnology of Infectious Diseases and Cancer-Immunological and Chemical Approach-

Immunosuppressive drugs to treat transplant rejection

Calcineurin inhibitors Ciclosporin (cyclosporin) Tacrolimus (FK506)

TOR inhibitors Sirolimus (rapamycin)

Frontier Race forLimited Resources

MercantilismColonialismImperialismFrontier in the West

Frontier Race forUnlimited ValueScience & Technology

Collaboration Network

Discovery & InnovationTranslation

US biotech industry grew afterLate 20th century based on openS & T policyScience is a growing tree nurtured by

society but Japanese society wanted to just have the fruit E. Bertz 1901

Europe

US

Necessity triggers Invention Innovation creates Necessity

Biotechnology is the Network Industry

IMSUT (Anti-Sera Therapy), Riken(VB1)Ajinomoto (MSG), Sankyo Pharma

Biotech industry grew in early 20th century in Japan

Pasteur, Koch

19th Century

Infectious Diseases

20th Century

1950 Molecular Biology1970 rDNA Technology 1990 Genome Science

Watson, Crick, Kornberg, Berg

Common Agenda for R & D in Asia

21st Century2000 Stem Cell Science2010 Systems Sciences

Bioventure in USA

In Stanford/Silicon Valley, BT revolution followed IT revolution. In 50s, Syntex emerged with steroid chemistry and in 60s, ALZA emerged with DDS. In 70s, Genentec, Amgen, Cetus, Chiron, DNAX etc started by employing rDNAtechnology. As a result, novel Biotech Drugs (GFs, Insulin, EPO, G-CSF etc) were developed, and this new industry created ecosystem of ventures such as reagent services (Affymetrix), gene libraries (Clonetec), analytical tools (ABI). On the other hands, pharmaceutical companies based on chemistry were located in east coast (New Jersey).

In Silicon Valley of 80s, positive cycle of High-risk High return worked well; i.e. investment on innovation to create new value and recover the investment for next cycle

Discovery

New Products

Double helix Genetic codeDNA polymeraseSplicingRibozyme

Translational Research

Cloning SequencingPCRSELEX Gene targeting

Biotechnology industry in Silicon Valley

Genome Diagnosis Genomic DrugsGene TherapyCell Therapy Regenerative Medicine

Alejandro ZaffaroniDDS, DNA chipEntrepreneuer

Paul BergGenetic Engineering1980 Nobel Prize

Arthur KornbergDNA polymerase1959 Nobel Prize

Gene Hunters and the Golden Age

Three Elements for Venture1. Open & Top University attracting Talents Worldwide 2. Access to Int’l Airport within 30 min 3. Favorable Living Conditions

Innovation

After Meiji Era of late 19th century, Japan achieved high economic growth building strong knowledge base, armed with high technology, well trained human resource and relatively inexpensive labor cost. In BT area, organic chemistry based pharma and food industry had been developed, however bioventuresystem was not developed even in 1980s although high quality life science research based on molecular biology and rDNA technology was strong.

Bioventure in Japan & Asia

Japan

Bernard Experimental MedicineVirchow Cell Pathology Mendel GeneticsPasteur MicrobiologyKoch Bacteriology

Infectious Diseases

European roots

Big Pharmas in Japan

Takeda AstellasDaiichi -Sankyo

Human Genome ProjectSNP Project

Genome Clinical Epidemiology

E. coli, Yeast, ArabidopsisC. elegans, Drosophila, Zebra fish, mouse

Model Organisms

Genome InformationUniversalityDiversity

Infectious Disease

Genome ScienceSystems BiologyHealth Sciences

Bernard Experimental MedicineVirchow Cell Pathology Mendel GeneticsPasteur MicrobiologyKoch Bacteriology

Molecular GeneticsBiochemistry

Molecular Biology

21st Century Medicine

Personalized Medicine

19th Century Medicine

20th Century Life SciencePharma industryBiotech venture

Generalized Medicine

Technology Platform for Genomic & Personalized Medicine

European roots

American roots

Change of the Concept of Drugs in Medical Frontier

Organic compound as a drug

Protein/antibodies as a drug

Gene as a drug

Cell as a drug

Organic chemistry

Genetic engineering(Biotech Drug)

Gene/DNA/RNA therapy

Cell therapy

Genomic Medicine

Genome databaseGene polymorphism

Cell Engineering

Genome Engineering

Stem cell Regeneraive Medicine

RNA engineeringProteomics

Cell & Gene TherapyRegenerative Medicine

Genome Diagnosis

Genomic Medicine

Molecular DesignGenomic Drug

Protein/RNA Engineering

3 Elements in Drug Development and Pharma Industry

CompetitivePharmaIndustry

R&D(Investment) Drug

development(Innovation)

Profit(Return)

Realizing society with health and

safety

Progress in life science

Economic Growth Source; Office of Pharmaceutical Industry Research

・Promote frontierresearch

・Ripple effect for related industry

Knowledge-based, high value added

industry.

Cure diseaseExtend healthy

life span

・Increased medical and pharmaceutical cost.・New growth market, mainly in Asia・Intensified competition of global pharma industry.

Novel pharma industry by partnership of 4 countries

Human Disease Model Center

Basic MedicalScience

Cancer/CellGrowth

Infection/Immunology

Human Genome Center

Research Hospital

Clinical ResearchFor TR

Basic Research Division

Frontier Medicine Research Center

TR SupportSystem

Infectious Disease Research Center

Translational Research Platform at IMSUT 2007by Dr. Yamashita, Director of IMSUT Research Hospital

a b

Core of TR

TR Support Center

Clinical Trials

Clinical Trial CenterInvestigator Driven Industry DrivenResearch Hospital

PharmaUniversityInstitutes Venture R Venture D

CRO

Discovery RLead

Proof of Concept（ POC ）

SeedsProductsDevelopment D

Phase 1 Phase 2 Phase 3 Phase 4Clinical Trial

Basic ResearchIn vitroAnimal Model

Clinical Application

Bridging Area (Clinical Research)

Process of Drug Development

Role of Drug Discovery Ventures in Pharma Industry

R&D expenditure and number of new product approvals by FDA of bioventure and major

pharmas in U.S.A

Decreasing: by big pharma co’s

Increasing: by venture companies

Number of bio-products by category of originator

Source：Pharmaproject (2007.2)

Drug Discovery Ventures: Cash Flow and Difficulties

Milestone revenues

Million Yen

Funding development cost from POC to milestone contract stage is difficult

Clinical trials starts

Partnering with big pharmas is required for IPO. Listing at early stage is impossible. Capital-raising amount is small due to low market cap level at IPO.

Japanese venture capital firms can supply capital only for search and R&D phases. Funding for clinical development stage is difficult.

(R&D infrastructure) Clinical testing is expensive and takes time. Capability of CRO is lagging.

Source: M’s Science

＜3 difficulties of drug discovery ventures＞

FY

＜Difficulty 1＞ Financing

＜Difficulty 2＞ Clinical trials

Contractsigning

＜Difficulty 3＞Exit plan

Three elements are required to develop new pharmaceutical industry in Asia

1. Pharmaceutical industry2. Innovative biotech ventures 3. Exit Strategy for biotech ventures

A Japanese Perspective on PostdocsScience Editorial in 1999: 285. p. 1487Ken-ichi Arai & Naoko Arai

Japanese career structure in global world

• Predictive: – Probabilistic health history--DNA sequence– Biannual multi-parameter blood protein measurements

• Personalized: – Unique individual human genetic variation mandates individual

treatment– Billions of data points on each individual patients

• Preventive: – Design of therapeutic and preventive drugs via systems

approaches– Targeted vaccines will be a critical preventive for infectious

diseases– Focus on wellness

• Participatory: – Patient understands and participates in medical choices

Predictive, Personalized, Preventiveand Participatory P4 MedicineLeRoy Hood, Institute of Systems Biology

Systems MedicineComplex, personalized

Information drivenTranslational platform

Regulatory agencyPharma & Bioventures

Traditional MedicineComplex, personalized

TCM,Oriental MedicineAlternative Medicine

Modern MedicineChemistry driven

Organic compounds as drugPharma Industry

Molecular MedicineBiotechnology driven

Biotech drugs, Bioventures

Genomic MedicineInformation driven, personalized

Translational platformGenomic drugs, Pharma & ventures

Vertical vs Horizontal R & D

New Combination & Network

Development of Biotech & Biomedical Industry

Frontier Medicine R/D Cycle・New Diagnosis/Therapy・New Drugs

Health Food & Lifeservice

DiagnosticService

Therapy

Concept of Drug/Therapy・LMW・protein・mAb・ODN・Cell

Therapy

Risk assessment

New Pharma/Tool Industry・BioVenture・Pharmas・Tool Industry

Health Information service・risk assessment

Survivor Care・risk

assessment・counsel・therapy

New Health Care Industry・Functional Food・Health Information

PreventionPrevention

UnivLife Science・

Medical Science

Health Care Cycle・Prevention・Foods・Life Style Consultation

IndividualPerson

Health Clinic

Personalized Health Care/Disease Prevention System

Hospital・Medical Information

Advanced Therapy・Long Distance

Therapy・Invasive

・

Development of New Bio-Pharma in East Asia

Chemistry

Protein Based

1900~

Nucleic AcidBased

TCMTKM

Organic Chemistry

Life Science

New Healthcare

venture

Cell Based

New BiotechVenture

1970~

Pharma

System Medicine

Cell Therapy

Drug DevelopmentImmuno-regulation

Cancer

Development of New Bio-Pharma in East Asia

Creation of an “Open Innovation Platform”

1) Introduction of drug seeds from Asia2) To conduct clinical trials from start to POC stage3) To encourage collaboration of pharma & bioventure4) To attract bioventures of Japan, Korea, Taiwan, Asia5) To prepare Exit Strategy to attract bioventures

・Open “Venture Business Authorization System” for foreign company currently limited to domestic one.・Allow listing overseas companies with operating deficits.This will create an Open Innovation Platform inviting foreign ventures and government support for Venture Capital Funds will encourage investment to innovative biotech ventures.

Exit Strategy

Yellow Sea

Shanghai

Taipei

Beijing

Seoul

Tokyo

Kyoto

Okinawa

Pohang

Personalized System Medicine for New Healthcare

China, Taiwan, Korea Korea, Japan, Taiwan

BT, IT, NT

Oriental Medicine

P4 MedicineLee Hood

PredictivePreventivePersonalizedParticipatory

GenomicMedicine

TCM, TKM

New Venture Fund with New Exit

Strategy

ventures and pharmas of Japan,

Taiwan, Korea

Strategy to Advance Bioindustry in East Asia

Basic R&DPre-clinical

Biotechnology Ventures

Phase I・IIa => POC => ApprovalManufactureSales

Universities,Major PharmasBioventures

Early or middle stage VCsFrom seeds to IND

application

Market

Later stage VCs Listing in Asia stock market

Asia PharmasPharmas in East Asia to have many pipelines and obtain blockbuster-

class earlier

The platform to incubates globally-competitive Pharmasof East Asia

Bioventures of Asia will form clusters around this platform

① Create positive cycle of investment and exit

② Create cooperative scheme with Asia Pharmas

Japan,Taiwan, China, Korea, Asia…

Open Innovation Platform

1. VCs support at early stage to develop pharma biotech.2. Pharmas supporting this stage can obtain many seeds for drug development at later stage.3. Synergy of 1 and 2 will attract more bioventures and create a positive cycle of investments.

Pharma Development in East AsiaNetworking Korea, Japan, Taiwan, China

Shanghai

Innovative Pharmaceutical

Industry

Global Open Innovation NetworkNetwork for creating novel robust pharma industry

Pharma in East Asia and Global Development

To ChinaTo Asia

Small pharmas of Japan, Korea, Taiwan with cutting-edge technologies× Development and management know-how of small pharmas of Japan, Korea× Network, mass-production know-how, marketing skills of Taiwan Companies× Co-investing with global pharmas of Taiwan, Korea and Japan

⇒ Expand business globally including China market

Manufacturers in Taiwan

Big Pharmas

Small Pharmas

To U.S.A.

Manufacturers in Korea

By Keiko OishiCMIC Co Ltd

Evolution of Clinical Studies in JapanWhere is Japan Clinical Development going?

Full-DevelopmentBridging Study (Retrospective, Prospective)Global StudyMultinational Clinical Trials in Asia

How to Share Common Biotechnology Platform in Asiabuild Translational Research Centers for Genomic MedicineNetworking Biomedical Centers for Clinical Trials

How to Organize Regulatory Environment & InfrastructureIP issues, Safety Evaluation, build FDA/CDC like network in Asia

Roche & Hutchison MedPharmaPudong, Shaghai

Big Pharmas & BioventuresIn Japan

Tasly, Tenjing,

Biocon, Bangalore, India

Syngene, Clinigene, Biocon

New Pharma Industry in Asia Harmonization, Clinical TrialsCommon Market

Big Pharmas & BioventuresIn US & Europe

Takeda, Astellas, Daiichi Sankyo, EizaiOTS, SBIBT,

Pharmas & BioventuresIn China

Astellas

ViroMed, Seoul, Korea

Exelixis, California

Theva, Israel

Systems BiologySeattle

Th1, Th2 and Th17 Differentiation Th1, Th2 and Th17 Differentiation

Regulation of TH17 DifferentiationRegulation of TH17 Differentiation

TregTreg DC/APCDC/APC

cDC Tnaive Teffector

Treg

Signals

pDC Tnaive

PathogenCancer

VirusCpG

CTL

CD4CD8

CD4

CD4

CD8+

CD8-

Pro-CancerPro-InfectionToleranceCell Transfer

-

Anti-CancerAnti-ForeignAnti-InfectionAutoimmune

IFN Antiviral activityAutoimmune Disease

IKDC NK

NKT

Cancer

Cancer Vaccine

Viral Vaccine

Cancer

ccImmune Network & Therapy for Cancer, Infection, Autoimmune Diseases

Cancer Cells

Y

YY YYY

Therapeutic AntibodyILT7, BST2

Anticancer DrugCdc7/ASK

Immuno-cell TherapyDC Therapy

Immune-modulatoryNucleic Acid Therapy

GNKG168

Drug Discovery & Technology Platform of SBI Biotech to develop drugs for Cancer and Immunological Diseases

Progenitor

Blood

Tissue

CD34+ myeloid CD34+ lymphoid

Mono

Interstitial DC

M?Langerhans cell

Plasmacytoidpre-DC

Plasmacytoid DC

CD11c+imDC

M-CSFGM-CSF IL-4

TGF-IL-3

Flt3LFlt3L

CD1a+ CD1a-

GM-CSF IL-4

CD11c-

CD34+ “lymphoid”

Virus

Myeloid Plasmacytoid

From N. Kadowaki

DC subsets (human)

Viral / Bacterialstimulation

・IFNα production

・M and NK cell activation

・ Antigen presentation

・T / B cell activation

Innate immunity

pDC Maturated pDC

Interferon-Producing Cell (IPC) / Plasmacytoid DendriticCell (pDC)

Acquired immunity

TLR1/TLR2

TLR3TLR4

TLR5TLR6/TLR2

BLP

dsRNA LPSFlagellin Diacylate

d BLP

TLR8

Imiquimod

NF-kB

Human pDC/IPC express TLR9 and TLR7, and IRF-3 and IRF-9

TLR7

TLR9

CpG(anti-Cancer)

Imiquimod(cutanesou viral diseases)

NF-kB

TNF- α, IL-1, IL-6, IL-12DC1

IFN-α/β/ωDC2

Kadowaki N et al J. Exp. Med, 2001.

Monocytes/pre-DC1 IPC/pre-DC2/pDC

IRF-3, IRF-7

ILT7

Gene Y

IFN

IFN target gene

CpG Virus

Self DNA

TLR7/9

New therapeutic target X

Anti-ILT7 Ab

Anti-gene Y Ab

IFN

TLR Antagonist

Immune reaction

Anti-tumor effects

Immune reaction

Autoimmune disease

pDC

TLR Agonist

pDC as a Target for Drug Development (mAb and CpG)

GNKG168GNKG168 is CpG ODN that stimulates Toll like receptor 9 (TLR9), induces the apoptosis of malignant B-cells

Treatment for B-cell Lymphoid Leukemia

Monocyte

ImmatureDC

MatureDC

Tumor Ag

GM-CSFIL-4

Inflammatory CKSCD40 ligand

In 2000s Vaccines for Viral Diseases & Cancer

Cancer Immunotherapy by DCs

K. Palucka & J. BanchereauK. Palucka & J. Banchereau

BIIR（Baylor Institute of Immunology)Baylor Research Institute (Dallas)

ImmunomonitoringImmunomonitoringSpecific: EPIMAXSpecific: EPIMAX

NonNon--specific: specific: MicroarraysMicroarrays

Ten color flow cytometryTen color flow cytometry

VaccineVaccinecGMPcGMP

Closed systemClosed systemFrozen vaccineFrozen vaccine

Clinical CoreClinical CoreRegulatory group: Regulatory group:

INDsINDsMulticenter trialsMulticenter trials

BCOGBCOG

BIIR cancer programBIIR cancer program

Clinical research and trial at public sectors and private clinics in Japan is planned in collaboration with BRI

SBI Biotech produce Asian synergy on DC therapy by establishing immunotherapy consortium in Japan, Korea and Taiwan

DC Therapy

IMSUTKyoto University Hospital

Private Clinics

License Agreement

JapanKorea

Taiwan

Classic vaccines

DCs as random targetsDCs as random targets

DCs as vectorsDCs as vectors

Specific DC targetingSpecific DC targeting

Banchereau and Palucka Nat Rev Immunol 2005

Therapeutic

Preventive

THE CENTRAL ROLE OF DENDRITIC CELLS IN VACCINATION

MonocyteMonocyte

Activated Activated monocytemonocyte

ActivationActivationGMGM--CSFCSF

ILIL--33FLT3FLT3--LL

IL4IL4--DCsDCs

ILIL--44

IFNIFN--DCsDCs

IFNIFN--

TNFTNF--DCsDCs

TNFTNF

IL15IL15--DCsDCs

ILIL--1515TSLPTSLP--DCsDCs

TSLPTSLP

Interstitial DCsInterstitial DCs Langerhans cellsLangerhans cells

TSLPTSLPT cellsT cells

IL4IL4T cellsT cells IFNIFN

T cellsT cells

TNFTNFT cellsT cells

IL15IL15T cellsT cells

MonocyteMonocyte--derived DC vaccinesderived DC vaccines

Apheresis Apheresis

Culture Culture

Elutra Elutra

DCDCFreezingFreezing

Storage LN2Storage LN2Accelerated stability Accelerated stability

Fraction 2Fraction 2

Fraction 3Fraction 3

Fraction 4Fraction 4

Fraction 5Fraction 5MonocytesMonocytes

MonocyteMonocyteFreezingFreezing

LongLong--termtermStorageStorage

LN2 LN2

LymphLymphFreezingFreezing

LongLong--termtermstorage storage

LN2LN2

Monocyte isolation and processing Monocyte isolation and processing

Sterilization RmSterilization Rm

Cuture Rm 2Cuture Rm 2

PrePre--culturecultureRmRm Culture Rm 3Culture Rm 3

Management Management RmRm

Supply Rm 1Supply Rm 1

Supply Rm 2Supply Rm 2

Culture RmCulture Rm 11

EntranceEntrance

Cell PreserveCell Preserve

Kyoto University Hospital CCMTKyoto University Hospital CCMT

Visit of M. Ramsay to Kyoto Univ. HospitalKadowaki & Kitawaki lab CCMT and Maekawa team & Kitawaki lab

CCMT and Maekawa team

1992MelanomaDiagnosisSurgery

09/02BiopsyProven

MetastaticMelanoma

M1b

12/02Progressive

Disease DTIC

CisplatinVelban

IL-2IFN-a

02/03Progression

CurrentDC

Vaccinetrial

10 years1 4 4 4 4 4 4 7

11/03PR

35 months near CR

without any additional treatment

Palucka et al. J Immunotherapy 2006

Baseline After 8 vaccines October 2005

October 2005

MonocyteMonocyte--derived DCs loaded with killed allogeneic derived DCs loaded with killed allogeneic melanoma cells can induce durable clinical responsesmelanoma cells can induce durable clinical responses

After 7 vaccines 10 months laterBaseline

12/00MelanomaDiagnosisSurgery

03/01ProgressionSentinel LN

No metastaticDisease Surgery

06/02Progression

DTICCisplatinVelban

IL-2IFN-a

Surgery

04/03Progression

CurrentDC

Vaccinetrial

07/01In-transit

MetastaticDiseaseBiopsyproven

08-11/01MelphalanPerfusion

IFNProgression

01/02

Peptide-pulsedDC vaccine

4 4 4 4 4 4 8 7

01/04CR

18 monthsCR without

any additionaltreatment

Palucka et al. J Immunotherapy 2006

MonocyteMonocyte--derived DCs loaded with killed allogeneic derived DCs loaded with killed allogeneic melanoma cells can induce durable clinical responsesmelanoma cells can induce durable clinical responses

•• DC vaccines are safeDC vaccines are safe

•• DC vaccines elicit immune responsesDC vaccines elicit immune responses

•• Low rate of clinical responsesLow rate of clinical responses

How to improve the efficacyHow to improve the efficacyof DC vaccination in cancer?of DC vaccination in cancer?

Banchereau and Palucka, Nat Rev Immunol 2005

Conclusions from early clinical trialsConclusions from early clinical trials

Treg TeffTreg Teff

TeffTreg

CLINICAL RESPONSE

From Dr. Hideki Ueno, BIIR

Late Stage Cancer Patient

Treg Dominant

Break Treg Dominace

How to Improve Immunocell TherapyAnti Cancer Immunity

From Treg Dominance to Teff Dominance

Multi-potential Stem Cell

Transient AmplifyingCell

Cancer Stem Cell

CSC

Differentiated Cell

Amplifying Cancer Cell

CancerPrecursor Cell

? CyclingResting

Anti-cancer Drug

Stem Cell TherapyRegenerative Medicine

DC therapy

ES, iPS cell

Normal Stem Cell vs Cancer Stem Cell

Anti-cancer Drug

DNA2nCell

CycleDNA4n DNA

2n

DNA2n

DNA Replication Cell Division

G0

DNA2n

G1 S G2 M

CDC7/ASK Microtuble

X X

Normal CellCancer Cell Apoptosis Apoptosis

Survival Survival

Stem Cell Survival Survival

Anti-cancer Drug

Anti-cancer Drug

Normal Cell vs Cancer Cell: Cell Cycle Control

Immunotherapy Platform of SBIBT for Cancer

To create novel & global pharma industry in East Asia

Thank you!