EV71 Vaccine Development Weining Meng DCVMN 15 th Annual General Meeting 29 th October, 2014
Sinovac-A leading vaccine company in China Our Products: Hepatitis An Integrated Vaccine Company Our Products: Influenza A R&D Oriented company A Nasdaq Listed Company We are: 1 st company to develop inactivated hepatitis A vaccine in China 1 st company to develop combined hepatitis A and B vaccine in China 1 st company to complete phase I clinical trial on SARS vaccine worldwide 1 st company to develop H5N1 vaccine in China 1 st company to develop and get license of H1N1 vaccine worldwide 1st and only Chinese vaccine company listed in Nasdaq 2
Our Mission Supply Vaccines To Eliminate Human Diseases Provide Chinese Population with International Quality Vaccines Provide Vaccines Made in China to Worldwide Our Products: Hepatitis Our Products: Influenza 3
Manufacturing Facilities Manufacturing Plants Headquarter- Beijing Healive production plant Dalian Vero Cell Cultured Vaccine and Live Attenuated Vaccine Capacity:10 million Filling & Packaging Plant Beijing Dalian Capacity :6-15 million Tangshan Capacity :20 million Anflu Production plant Capacity :8 million R & D Center Changping District, Beijing Novel Vaccine Production Base Capacity of Filling and Packaging:100 million Capacity of EV71:10-20 million Building Area: 95,000 square meters Tangshan Yi an Animal Vaccine Capacity:5-20 million Building Area: 13,500 square meters Building Area: 29,000 square meters 4
Hand Foot Mouth Disease Epidemic US, EV71 was isolated 1969 Taiwan, 80677 cases, 41 deaths 1957 1975 1997 1998 2000 2007 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 Mainland of China, Korea, Viet Nan, etc. millions cases reported and thousands dead
EV71 Epidemic In China 2007-2014 HFMD Reported 年手足口病报告发病 死亡数统计 Cases and Fatal Cases 2007-2014 Total Serious Death 2500000 发病数 Reported Cases 死亡数 Fatal Cases 1000 900 2000000 800 Reported Cases 发 病 数 1500000 1000000 500000 700 600 500 400 300 200 100 Fatal Cases 死 亡 数 EV71 EV71 EV71 0 2007 2008 2009 2010 2011 2012 2013 2014 0 2007-August,2014, In total 11 millions HFMD reported,with more than 3,100 fatal cases 截止 8 月份 Serious HFMD epidemic in China; Mild cases:45% are EV71 Serious cases:80% are EV71 Fatal cases:90% are EV71 EV71 inducing main serious and fatal cases; Vaccine against EV71 is the answer. Hand, foot, and mouth disease in China, 2008 12:An epidemiological study
Development Milestones Pre-clinical study Clinical study IND Application NDA Application 2013.5 申请生产 Industrialization
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
Phase III Phase III 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 广西 Objective: Protective effective Subjects:6-35 months babies Dose:400U 10077 subjects 江苏 Objective: consistency Subjective:6 months-5 years children Dose:400U 1400 subject s All trials following GCP 168 subjects 540 subjects
EV71 Vaccine-Safety 发生率 100.0% 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% Local Adverse Reactions Systemic Adverse Reactions 疫苗组 安慰剂组 发生率 100.0% 90.0% 80.0% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 7.04% 6.94% 4.96% 5.66% 4.93% 5.06% 2.77% 10.0% 2.76% 2.16% 2.07% 0.0% 发红硬结疼痛肿胀瘙痒 疫苗组 安慰剂组 Vaccine Placebo Vaccine Placebo Red Scleroma Pain Swelling Itching 36.4% 36.1% 11.7% 12.0% 8.5% 8.6% 7.5% 7.0% 7.4% 7.4% 3.3% 3.6% 1.5% 1.33% 发热腹泻食欲下降烦躁恶心呕吐疲倦过敏 Fever Diarrhea Anorexia Irritable Vomit Fatigue Anaphylaxis No significant difference between vaccine group and placebo group Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China, The New England Journal of Medicine, 2014
EV71 Vaccine-Efficacy No. of Cases 病例数 100 90 80 70 60 50 40 30 20 10 0 Protection rate:94.3% 94 5 疫苗组 vaccine 对照组 Control Effectiveness for EV71 Infection No. of Cases 病例数 100 90 80 70 60 50 40 30 20 10 0 Protection rate:100.0% 24 0 疫苗组对照组 vaccine Control Effectiveness for hospitalized cases Protection rate for EV71 infection: 94.3% Protection for hospitalized cases and serious cases:100.0% Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China, The New England Journal of Medicine, 2014
GMT 阳性率 EV71 Vaccine-Immunogenicity 180 100.00% 160 140 120 100 80 60 Control 对照组疫苗组 Vaccine Positive Rate 90.00% 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% Control 对照组疫苗组 Vaccine 40 20.00% 20 10.00% 0 0.00% Pre-vaccination Pre-vaccination 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. Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China, The New England Journal of Medicine, 2014
Industrialization Production 19000 m2 4F Ready for use Others 4000 m2 2F Animal Lab 1F Biobank Office 9000 m2 Total :29,021 m2 Built-up area:32,322 m2 3F 2F 1F QC Labs EV71 Bulk 20 million does/year Formulation Filling & Packaging 100 million doses/year Cold Room 1.8 million vials Utilities