EV71 Vaccine Development

Weining Meng

DCVMN 15th Annual General Meeting

29th October, 2014

A R&D Oriented company

A Nasdaq Listed

Company

An Integrated

Vaccine Company

Sinovac-A leading vaccine company in China

2

Our Products: Hepatitis Our Products: Influenza

We are: 1st company to develop inactivated hepatitis A vaccine in China 1st company to develop combined hepatitis A and B vaccine in China 1st company to complete phase I clinical trial on SARS vaccine worldwide 1st company to develop H5N1 vaccine in China 1st company to develop and get license of H1N1 vaccine worldwide

1st and only Chinese vaccine company listed in Nasdaq

Our Mission

3

• Provide Chinese Population with International Quality Vaccines

• Provide Vaccines Made in China to Worldwide

Supply Vaccines To Eliminate Human Diseases

Our Products: Hepatitis Our Products: Influenza

Manufacturing Facilities

4

Manufacturing Plants

Dalian

Vero Cell Cultured Vaccine and Live Attenuated Vaccine

Capacity：5-20 million

Building Area: 13,500 square meters

Headquarter- Beijing

Beijing

Dalian

Tangshan

Healive production plant

Capacity：10 million

Filling & Packaging Plant

Capacity ：20 million

Anflu Production plant

Capacity ：8 million

Tangshan

Yi’an Animal Vaccine

Capacity of Filling and Packaging：100 million Capacity of EV71：10-20 million

Changping District, Beijing

Novel Vaccine Production Base

Capacity ：6-15 million

R & D Center

Building Area: 29,000 square meters

Building Area: 95,000 square meters

Hand Foot Mouth Disease Epidemic

New Zealand, Hand Foot Mouth Disease was reported and defined

Bulgaria, 705 cases, 44 deaths

Malaysia, 2628 cases, 30 deaths

Taiwan, 129106 cases, 78 deaths

Taiwan, 80677 cases, 41 deaths

US, EV71 was isolated

1969 1957 1975 1997 1998 2000

Mainland of China, Korea, Viet Nan , etc. millions cases reported and thousands dead

2007

EV71 Epidemic In China

2007-August,2014，

In total 11 millions HFMD reported，with more than

3,100 fatal cases

《Hand, foot, and mouth disease in China, 2008–12:An epidemiological study》

EV71 EV71 EV71

Total Serious Death

Mild cases：45% are EV71 Serious cases：80% are EV71 Fatal cases：90% are EV71

Serious HFMD epidemic in China;

EV71 inducing main serious and fatal cases;

Vaccine against EV71 is the answer.

0

100

200

300

400

500

600

700

800

900

1000

2007 2008 2009 2010 2011 2012 2013 2014

0

500000

1000000

1500000

2000000

2500000

死

亡

数

发

病

数

2007-2014年手足口病报告发病、死亡数统计

发病数 死亡数

Rep

orted

Cases

Fatal Cases

截止8月份

HFMD Reported Cases and Fatal Cases 2007-2014

Reported Cases Fatal Cases

Development Milestones

2013.5 申请生产

Pre-clinical study

IND Application

Clinical study

Industrialization

NDA Application

Characters of Sinovac EV71 Vaccine

Vero Cell, cell factory cultivation technology;

H07 strain, C4 subgenotype, isolated by China CDC;

Inactivation with formaldehyde

Al(OH)3 as adjuvant

100 u/200u/400 u, 2 doses/3 doses regimen

EV71 Vaccine Clinical Trails

Phase I

• Objective：Safety, Immunogenicity

• Subjects：Babies, children, and Adult

• Dose：100U、200U、400U

Phase II

• Objective：Immunogenicity, safety

• Subjects：6-35 months babies

• Dose：100U、200U、400U

168 subjects

540 subjects

广西

Phase III

• Objective：Protective effective

• Subjects：6-35 months babies

• Dose：400U

Phase III

• Objective：consistency

• Subjective：6 months-5 years children

• Dose：400U

10077 subjects

1400 subject

s 江苏

All trials following GCP

No significant difference between vaccine group and placebo group

EV71 Vaccine-Safety

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

发红 硬结 疼痛 肿胀 瘙痒

7.04% 4.96% 4.93% 2.77% 2.16%

6.94% 5.66% 5.06% 2.76% 2.07%

疫苗组 安慰剂组

0.0%

10.0%

20.0%

30.0%

40.0%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

发热 腹泻 食欲下降 烦躁 恶心呕吐 疲倦 过敏

36.4%

11.7% 8.5% 7.5% 7.4%

3.3% 1.5%

36.1%

12.0% 8.6% 7.0% 7.4%

3.6% 1.33%

疫苗组 安慰剂组

Local Adverse Reactions Systemic Adverse Reactions 发生率 发生率

Vaccine Placebo Vaccine Placebo

Red Scleroma Pain Swelling Itching Fever Diarrhea Anorexia Irritable Vomit Fatigue Anaphylaxis

Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China, The New England Journal of Medicine, 2014

EV71 Vaccine-Efficacy

Protection rate for EV71 infection： 94.3%

Protection for hospitalized cases and serious cases：100.0%

5

94

0

10

20

30

40

50

60

70

80

90

100

疫苗组 对照组

病例数 病例数

Effectiveness for EV71 Infection

0

24

0

10

20

30

40

50

60

70

80

90

100

疫苗组 对照组

Protection rate：100.0%

Effectiveness for hospitalized cases

病例数

Protection rate：94.3%

vaccine Control vaccine Control

Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China, The New England Journal of Medicine, 2014

No. of Cases No. of Cases

EV71 Vaccine-Immunogenicity

56 days after vaccination，Neutralizing antibody positive rate 98.79%、GMT 165.79，

8 months and 14 months after vaccination, high level of antibody

Good immunogenicity and immune persistence.

0

20

40

60

80

100

120

140

160

180

GM

T

对照组

疫苗组

Pre-vaccination

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

90.00%

100.00%

阳性率

对照组

疫苗组

Positive R

ate

Control

Vaccine

Control

Vaccine

Pre-vaccination

Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China, The New England Journal of Medicine, 2014

Production 19000 m2

4F Ready for use

3F QC Labs

EV71 Bulk 20 million does/year

2F Formulation

Filling & Packaging 100 million doses/year

1F Cold Room 1.8 million vials

Utilities

Others

4000 m2

2F Animal Lab

1F Biobank

Office 9000 m2

Industrialization Total ：29,021 ㎡

Built-up area：32,322 ㎡