Regional prevalent diseases in Asia

Regional prevalent diseases in Asia:

Where do the key market opportunities lie?

Phacilitate’s 1st Asian Cell & Gene Therapy Forum Singapore, 2011

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Which diseases can and are being targeted with cell & gene therapies in Asia?

September 21, 2011

Dr. Milind Sabnis, MD, MBA

Principal Consultant

Healthcare, Asia Pacific

Agenda

• Introduction

• Global trends & impact on health care in Asia

• Key Diseases in Asia

• Gene therapy

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• Gene therapy

• Cell therapy

• Summary

GLOBAL TRENDS & IMPACT ON HEALTH CARE IN ASIA

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GLOBAL TRENDS & IMPACT ON HEALTH CARE IN ASIA

Percent of world GDP – Last 500 yearsChina, India, Japan, Latin America, Western Europe and United States

21%11%

Share of World GDP in

2005

15%27%

Share of World GDP in

2035

4

21%11%

6%

15%27%

15%

Source: Frost & Sullivan

Growing middle class is changing the mix in demand for healthcare services

• Creation of “healthcare elite”: those that can, will spend money out of pocket for elective procedures, executive and personalized levels of care.

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Changing demographics leads to changing disease patterns and health risks

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Aging population will account for around 20% of the world population in 2050

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2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

50.0

100.0

150.0

200.0

250.0

300.0

350.0

400.0

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65

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(%

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Po

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(M

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By 2020, two-third of the Asia-pacific population over 65 years will have at least one chronic disease

Healthcare Industry: Population Aged 65 and Above, (Asia Pacific), 2009-2020

The Burden of Disease in elderly, Asia Pacific

8

0.0%

2.0%

-

50.0

2010 2015 2020

Pe

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65

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Year

Aged 65 and Above (Million)

Percentage of Aged 65 and Above to Total Population (%)

� In 2010, 7.6% (241.7 million) of the Asia Pacific population was aged 65 and above.

� By 2020, this will be more than 9.7% (333.95)

� 65.2% of those aged 65+ have one chronic condition

Source: WHO, Frost & SullivanSource: Frost & Sullivan

Asia Pacific Healthcare Expenditure is growing

Healthcare Expenditure and Growth Rate by Country (2010 & 2015)

428.50

259.80

99.7058.22 58.02 58.00 36.50

571.20

561.90

139.50111.60 78.90

95.10 49.905.0

16.3

6.8

13.8

6.0

9.9

6.2

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

100.0

200.0

300.0

400.0

500.0

600.0

700.0

He

alt

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nd

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$ B

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Healthcare Expen diture by

Country

(CAGR %

)

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Note: All figures are rounded; the base year is 2010.

� Japan has the highest healthcare expenditure in 2010 and 2015, with 5% CAGR between 2010-2015China has the second highest healthcare expenditure planned.

� Among other Asia Pacific countries, China has the highest healthcare expenditure growth of CAGR of16.3% followed by India, with CAGR of 13.8% and SEA 9.9%

� The value of Asia Pacific healthcare expenditure is estimated at around $ 1080 billion in 2011.

58.22 58.02 58.00 36.50

-

2.0

0.0

Japan China ANZ India South

Korea

SEA* Others

He

alt

hca

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xpe

nd

itu

re (

$ B

illi

on

)

2010 2015 Healthcare Expenditure CAGR (%)

* SEA – South East Asia – Includes Singapore, Malaysia, Thailand, Indonesia and Philippines

Healthcare Expen diture by


Faster healthcare per-capita growth compared to per-capita income is unsustainable; healthcare needs innovative solutions

Healthcare Spending Per Capita (2007, 2050)

In most countries worldwide, per capita In most countries worldwide, per capita

healthcare spending is rising faster than per healthcare spending is rising faster than per

capita income which is unsustainable capita income which is unsustainable

If current trends hold If current trends hold -- by 2050, healthcare by 2050, healthcare

spending will double, claiming 20spending will double, claiming 20--30% of 30% of

GDP for some economies GDP for some economies

Innovative therapies such as gene therapy and cell therapy will help treat various currently untreatable diseases

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Due to rising costs of healthcare, future Due to rising costs of healthcare, future

spending will move away from spending will move away from

treatment treatment

Healthcare Spending by Type of Activity

Source: Frost & Sullivan.

KEY DISEASES IN ASIA

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KEY DISEASES IN ASIA

More DALY are lost due to cardiovascular diseases in Asia than in the rest of the world

Total DALYs (000s, all ages) lost due to cardiovascular disease in the Asia Pacific, 2005

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DALY=Daily adjusted life years; Cardiovascular diseases excludes rheumatic heart disease

• Globally, CVDs are the No.1 cause of mortality (~ 29% of all deaths)

• 82% of CVD deaths take place in low- and middle-income countries

• ~17.1 million deaths in 2004, expected to reach ~23.6 million by 2030

• The largest increase in number of deaths will occur in the South-East Asia Region

•Source: Health in Asia and the Pacific. Priority noncommunicable diseases and conditions. 2011. 287-332. Frost & Sullivan.

Lung, Stomach, and Liver cancers are the top three male cancers in Asia Pacific

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CancerAll

cancersLung Stomach Liver Colorectal Esophagus Prostate Bladder Leukemia

Lip, oral cavity

Non-Hodgkin

lymphoma

Incidence 3241249 604629 484411 416589 283596 247060 133212 101776 95941 91327 75866

Mortality 2353611 523899 342163 376006 144980 204919 59669 44316 76962 54518 50707

• Globally, ~ 7.6 million total cancer deaths (around 13% of all deaths) in 2008

• Deaths from cancer worldwide are projected to reach over 11 million by 2030

Source: GLOBOCAN 2008: Cancer incidence, mortality and prevalence worldwide; Frost &Sullivan.

Breast, Cervix/uterus, and Lung cancers are the top three female cancers in Asia Pacific

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CancerAll

cancersBreast

Cervix uteri

Lung Stomach Colorectal LiverCorpus uteri

Esophagus Ovary Leukemia

Incidence 2851110 528927 312990 268434 243154 225688 167851 131178 124507 102408 76111

Mortality 1718721 193497 159894 229778 188427 122034 157719 35044 103313 60142 60298

Source: GLOBOCAN 2008: Cancer incidence, mortality and prevalence worldwide; Frost &Sullivan.

• Lung cancer is the top cancer killer both in males & females in Asia

• More than 30% of cancer deaths can be prevented

Prevalence of diabetes is expected to continue to rise in Asia pacific and globally

Prevalence of diabetes (million) in Asia-pacificDiabetes

• 346 million people worldwide have

diabetes

• ~157 million people suffer from

diabetes in Asia Pacific

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• More than 80% of diabetes deaths

occur in low- and middle-income

countries

• Globally, ~ 3.4 million people died from consequences of high blood sugar in 2004

• WHO projects that diabetes deaths worldwide will double between 2005 and 2030


GENE THERAPY

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GENE THERAPY

Gene therapy

Genetic Disorders

Severe Combined Immune Deficiency (ADA-SCID)

Chronic Granulomatous Disorder (CGD)

Hemophilia

Other genetic disorders*

Cancer

Two-thirds of all current gene therapy trials are for various cancer indications

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Acquired Diseases Neurodegenerative Diseases

Other acquired diseases**

*Congenital blindness, lysosomal storage disease and muscular dystrophy, etc** Viral infections (e.g. influenza, HIV, hepatitis), heart disease and diabetes, etcSource: Frost & Sullivan.

Most gene therapy phase 3 trials are for cancer and cardiovascular diseases indications

Most Advanced Gene Therapy Products, March 2010

Product Name Constructs Company Indication Development Stage

Gendecine (genkaxin) Ad5p53Si Bono / Benda Pharmaceutical

Head & Neck Cancer

Marketed (China); 2003

Glybera (alipogen tiparvovec) AAV-mLPLAmsterdam Molecular

TherapeuticsLPL Deficiency MAA Filed with EMA

Collategene (beperminogen pHGF AnGes /Daiichi Sankyo

Peripheral Vascular BLA Submitted in Japan

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Collategene (beperminogen perplasmid)

pHGF AnGes /Daiichi SankyoPeripheral Vascular

DiseaseBLA Submitted in Japan

(2008) Phase 3 (U.S. / EU)

Allovectin-7 (velimogene aliplasmid)

Immunotherapy Vical / AnGesMetastatic Melanoma

Phase 3

TK-DLI (TBI-0301)HVS-TK

transfected HSCMolMed / Takara Bio Leukemia Phase 3

Generx (alferminogene tadenovec)

Ad5FGF-4 CardiumCoronary Artery

DiseasePhase 3

riferminogene pecaplasmid NV1FGF1 Sanofi - AventisCritical Limb

IschemiaPhase 3

LPL=lipoprotein lipase Source: http://www.cardiumthx.com/pdf/Most-advanced-gene-therapy-products.pdf;;accessed: June 2011.

• The first gene therapy to be marketed was in China

Another Adenovirus (Replication-competent adenovirus) was commercialized in China in 2005

Japan has a strong pipeline for gene therapy products in late stages of development

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Gene therapy clinical trials in Japan by stage of development

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*ASO/Buerger's Disease. c=Lung cancer (NSCC)(5); Esophageal cancer(1); prostate cancer(1); breast cancer(1); leukemia(1); glioma(1); melanoma(1). d=Prostate

cancer. e=Renal carcinoma. f=ADA Deficiency. SCID=Severe combined immunodeficiency. ADA=Adenosine deaminase . ASO=atherosclerosis obliterans

Source: Kim S, Peng Z, Kaneda Y. Current Status of Gene Therapy in Asia. The American Society of Gene Therapy. 2008;16:237–243. Frost & Sullivan.

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Target diseases

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Currently in Asia, Japan has the most gene therapy products that have completed phase 2 clinical trials/

entered phase 3; majority of these products are for cancer treatment

China approved the world first gene therapy for cancer treatment

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Gene therapy clinical trials in China by stage of development

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Target diseases

a

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a=Ischemic disease b=AIDS(1); Hepatitis B(1)Source: Kim S, Peng Z, Kaneda Y. Current Status of Gene Therapy in Asia. The American Society of Gene Therapy. 2008;16:237–243. Frost & Sullivan.

• World’s 1st approved gene therapy product (2003) gendicine (recombinant human p53 adenovirus)

• Chinese Government's 863 Program: In 2007, ~$52.0 million was allotted to projects in 11 priority

biotechnology areas, including gene therapy and cell therapy for major diseases

Korea has a few gene therapy products in early stage of development

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Gene therapy clinical trials in Korea by stage of development

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j

h

l

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Source: Kim S, Peng Z, Kaneda Y. Current Status of Gene Therapy in Asia. The American Society of Gene Therapy. 2008;16:237–243. Frost & Sullivan.

b=AIDS(1); g=Prostate cancer. h=melenoma (1); melanoma, breast cancer,head-and-neck cancer (1). i=liver cancer. j=Ischemic limb disease. k=coronary artery

disease. l=Chronic granulomatous disease. m=osteoarthritis.

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Target diseases

j

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Currently, Korea has 3 products in phase 2 funded mainly by small sized venture companies;

pharmaceutical companies are still hesitant about getting involved in gene therapy

CELL THERAPY

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CELL THERAPY

Cell Therapy

Hemophilia A,B: blood transfusion

Leukemia, Lymphoma: bone marrow transfer

Thalassemias

Most common cell therapies are targeted toward blood disorders

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SCID

Others*

*Skin, Eye, orthopedics, cerebral palsy, diabetes, etc ; eg. skin regeneration and healing (Apligraf®), diabetic foot ulcers

(Dermagraft®, skin substitute), nasolabial fold wrinkles (LaVív),cerebral palsy (umbilical cord blood transplantation), etc

• Most cell therapies are for treating hemophilia, leukemia, lymphoma, thalassemias

• Both approved and experimental stem cell products are used in Asia to treat multiple disorders


FDA has approved only two cellular therapy products

Cell Therapy Products that recently got FDA approvals

Product Name Constructs Company Indication

PROVENGE

(sipuleucel-T)

Only FDA approved

Autologous, cellular,

immunotherapy

(2010)

Dendreon

Treatment of asymptomatic or minimally

symptomatic, metastatic, castrate resistant

(hormone refractory), prostate cancer.

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(2010)

LaVív

(azfibrocel-T)

Autologous cell therapy

(2011)Fibrocell Science, Inc.

First FDA approved autologous cell therapy for

the treatment of moderate to severe

nasolabial fold wrinkles in adults

• LaViv a recently (2011) approved cell therapy drug is for treating naso-labial fold wrinkles

• Apligraf® (1998) & Dermagraft® (2001) are cell therapies (classified as devices by FDA) for treating

diabetic foot ulcers

• Skin disorders could be the other focus area for cell therapy in Asia


Asides approved cell therapies, experimental cell therapies are widely used in Japan and China

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*In Japan, autologus cell therapy can be regulated as clinical treatment under doctor’s own decision. Hence Japan is thought to be a easy country to run clinical application without regulatory control. In fact, a Korean company is running its trial in Japan; but recently the Korean government committed nearly 100 billion won (S$111.7 million) in stem cell research next year and ensured to reform related regulations to make clinical and licensing procedures easier**VistaStemCell, a company in China, claims to treat (with cell therapy) multiple conditions that include neurological diseases, endocrine diseases, cancer, immune system diseases, others including myocardial infarction, femoral head necrosis, kidney disease, liver disease † 2009: The Chinese Ministry of Health has implemented regulations on the clinical application of stem-cell injections. The new regulations, designate all forms of stem-cell therapy as 'category 3' medical technologies — those deemed "ethically problematic", "high risk" or "still in need of clinical verification". The ministry will take direct responsibility for regulating all category-3 procedures, which include cell & gene therapy. Source: Frost & Sullivan.

†

Hospitals in some countries in Asia with various stem cell therapy facilities

In Asia, most common cell therapies available at hospitals are for the treatment of blood disorders and heart diseases

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*Cerebral Palsy, Diabetes, Motor neuron disease, Multiple Sclerosis, Parkinson's Disease, rejuvenation therapy

• In some Asian countries, hospitals offer cell therapies in multiple areas


In Asia, there are multiple stem cell banks that collects, processes and stores stem cells for potential future use

StemLife Berhad(Malaysia) –SECRETARIAT OF THE APCBBC

BIONET Corporation (Taiwan)

Cordlife Pte Ltd (Singapore) / PT. Cordlife (Indonesia)Banks in: China, Hong Kong.Being extended to India &Indonesia

CryoLIFE (Hong Kong)

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LIFECORD (Korea) StemCellInstitute Ltd (Japan)

THAI StemLife(Thailand)

StemOneBiologicals(India)

• Multiple private stem cell/cord blood bank exist in Asia


Summary

� Asia Pacific shows the highest mortality rate from non-communicable diseases compared with

other regions

� Cardiovascular diseases, cancer, and diabetes are the top 3 non-communicable diseases in Asia

� Two thirds of the gene therapy clinical trials are in cancer; most phase 3 gene therapy trials are in

cancer and cardiovascular diseases

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� In Asia, most common cell therapies available at hospitals are for the treatment of blood disorders

and heart diseases; skin disorders could be another area of focus

� Asides approved cell therapies, experimental cell therapies are widely used in Japan and China

� Cell therapy and gene therapy has enormous opportunity in Asia because of the large target

population and comparatively relaxed restriction on the use of experimental products

� However, regulators in Asian countries should be cautious to prevent misuse that could bring

disrepute to the use of these innovative therapies that hold immense promise for the future

For additional information

Dr. Milind Sabnis, MD, MBA

Principal ConsultantHealthcare, Asia [email protected]

Donna Jeremiah

Corporate Communications

Asia Pacific

+603 6204 5832

[email protected]

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Jessie Loh


Asia Pacific

+65 6890 0942

[email protected]

Carrie Low


Asia Pacific

+603 6204 5910

[email protected]

Health & Medicine

Regional prevalent diseases in Asia