Pfizer s Investigational Vaccine, rlp2086, for Invasive Meningococcal Serogroup B Disease

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1 Pfizer s Investigational Vaccine, rlp2086, for Invasive Meningococcal Serogroup B Disease Laura J York, PhD Sr Director, International Scientific & Medical Affairs 1

2 Serogroup B is now the predominant remaining meningococcal serogroup in several parts of the world Y (13%) Other (13%) C (20%) B (54%) Y (3%) C (17%) Other (4%) B (76%) Y (25%) Other (9%) C (31%) B (35%) United States , 26 n = 1,172 Canada n = 210 Y W135 (2%) (2%) European Union n = 5,223 Other (1%) W135 (8%) Other A (1%) (2%) W135 (31%) Y (11%) C (3%) B (52%) Taiwan 27, n = 43 C (26%) B (69%) A (91 %) African Meningitis Belt Latin America and the Caribbean* 8 n = 2, n = 1,391 Australia n = 304 Other C (9%) (8%) New Zealand n = 105 Note: *Number of cases is an average of Isolates were collected from 19 countries and the Caribbean Epidemiological Center. Most isolates were from Brazil and Chile. Source: 14 EU-IBIS (2006); 24 CDC (2010) MMWR 57(54); 25 CDC ABCs Reports; 26 Public Health Agency of CA (2009) CCDR; 27 Chiou, CS. et al. (2006) BMC Infect Dis; 8 Harrison, LH et al. (2009) Vaccine; 28 WHO, Africa (2009); 29 AU Government Department of Health and Aging (2009); 30 NZ Ministry of Health (2008). B (84%) Other C (6%) (11%) B (83%)

3 Age-specific Incidence of Serogroup B Meningococcal Disease in the EU EU EU-IBIS Invasive N.Menigitidis in Europe Reports;

4 Number of Cases Significant MnB Disease Burden in Adolescents and Young Adults (EU, average number of cases ) <1 yr 1-4 yrs 5-9 yrs yrs yrs yrs 65+ yrs EU-IBIS Invasive N.Menigitidis in Europe Reports;

5 Meningococcal Carriage Rates Are Highest in Adolescents Prevalence (%) Vaccination of adolescents has the potential to provide direct and indirect (herd immunity) benefits Age (Years) Modified from Christensen et al. (2010). Lancet Infect. Dis. 10:

6 Serum Bactericidal Screen Was Used to Identify Pfizer s MnB Vaccine Candidate N. meningitidis Serogroup B Extract and Fractionate Immunize Mice hsba Screen Against Diverse MnB Important Target Antigen Attributes Surface exposed Highly conserved Expressed universally in diverse strains Induces serum bactericidal activity Fletcher et al. 2004; Bernfield et al

7 LP2086 Is a Factor H Binding Protein and MnB Virulence Factor fhbp/lp2086 binds human factor H LP2086 expressed during infection Factor H binding to LP2086 protects MnB from complement attack Functional anti-lp2086 antibodies protect via two mechanisms Inhibition of factor H binding to bacteria Serum bactericidal killing PorA fhbp/lp2086 Madico et al. 2006; Schneider et al. 2006; Mascioni et al. 2009; Seib et al. 2009; Ala Aldeen et al. 2010; McNeil et al. 2009; Jacobson, Moellig, Olcen

8 fhbp/lp2086 Protein Sequences (Variants) Segregate into Two Distinct Subfamilies LP2086 gene is present in > 2500 MnB invasive disease strains studied > 200 variants identified Two subfamilies, A & B Sequence identity between subfamilies 60-75% Sequence identity within subfamily >84% Two lipidated LP2086 variants selected (one from each subfamily) to assure immunogenicity and broad strain coverage B10 B13 B15 B09 B07 B05 B44 B02 B03 B B16 B24 A04 A05 A06 Subfamily B A29 A02 A01 A22 A20 A17 A19 A15 A12 A10 A07 A26 A09 Subfamily A 8 Murphy et al. 2009; Jiang et al. 2010

9 hsba GMT Titer Broad Protection Against Diverse, Invasive MnB Strains Requires an LP2086 Protein From Both Subfamilies Vaccine: rlp2086a rlp2086b rlp2086a and rlp2086b A05* A07 A17 A19 A22 LP2086 Subfamily A Expressing SBA Strains B01* B02 B09 B16 B24 LP2086 Subfamily B Expressing SBA Strains *Vaccine homologous LP2086 Variants Jiang et al. 2010

10 Pfizer s Bivalent rlp2086 Investigational Vaccine Elicits Broad hsba Activity Subfamily B 71% B44 B02 B107 B10 B08 B09 B07 B05 B01 B52 B13 B15 B03 B16 B24 Strains killed expressing vaccine homologous LP2086 variants Strains killed expressing vaccine heterologous LP2086 variants A62 A Genetic Distance A04 A63 A28 A05 A56 A06 A29 A42 A76 A02 A01 A08 A07 A20 A17 A19 A15 A12 A10 A26 Subfamily A 29% McNeil et al. 2009; Jiang et al

11 Pfizer s Development Strategy Focus on adolescent/young adult population Substantial disease burden High morbidity and mortality Highest meningococcal carriage rates Potential to affect disease burden in very young (<6 months of age), and throughout the community 11

12 Phase 2 MnB Vaccine Study in Adolescents (B ) Proof of Concept Randomized, single-blind, placebo-controlled trial conducted in Australia, Spain and Poland 535 Healthy Subjects, 11 to 18 Years of Age Safety, tolerability & immunogenicity of 3 doses 0, 2, 6 month immunization schedule 60, 120 or 200 µg dose in small sentinel cohorts; randomization 2:1 120 or 200 µg dose in expanded cohort; randomization 2:2:1 Study Objectives Primary Objective Assess immunogenicity of MnB vaccine by hsba Secondary Objectives Assess immunogenicity of MnB vaccine by IgG Assess safety and tolerability of MnB vaccine Richmond et al

13 % of Subjects with the Fever Percentage of Adolescents Reporting Fever (B ) Severity of Fever Within 1-7 days /197 a 2/192 1/118 2/193 1/189 1/102 2/ mcg Placebo 200 mcg 120 mcg 60 mcg Placebo 200 mcg 120 mcg 60 mcg Placebo 200 mcg 120 mcg Dose 1 Dose 2 Dose 3 a number of severe reactions/number of immunizations at dose level No fever >40.0C Richmond et al

14 rlp2086 Was Immunogenic in Adolescents hsba Responses to MnB Bearing Diverse fhbp Variants, Dose Selection for Completion of Clinical Program (B ) Control 120 µg dose (0, 2 6 months) % hsba 1:4 SBA Test Strain PD3 PD2 PD3 A (6.3, 21.2) (81.9, 93.5) (92.2, 99.1) A04 * (8.6, 28.1) (93.5, 100.0) (93.1, 100.0) A56 * (8.2, 25.3) (89.2, 98.1) (93.8, 99.8) B02 * (2.7, 14.3) (71.4, 85.8) (85.4, 95.8) B03 * (4.0, 18.3) (24.9, 43.0) (65.1, 83.3) B44 * (2.0, 13.5) (61.2, 78.6) (81.4, 93.8) * MnB strains expressing fhbp/lp2086 variant heterologous to vaccine antigen 14 Richmond et al 2011

15 Responder Rate (%) rlp2086 Was immunogenic in Adolescents hsba Responses to MnB Bearing Diverse fhbp Variants (US Study 2001, subjects 11 to 18 Years of Age) 100 % of subjects with hsba titer > 1: Predose 1 Postdose PMB2707 PMB1256 PMB1745 PMB1321 PMB2948 PMB17 PMB3302 PMB2001 B44 * B03 * A05 A22 * B24 * B02 * A04 * A56 * 15 * MnB strains expressing fhbp/lp2086 variant heterologous to vaccine antigen Jansen MRF Conference 2011

16 rlp2086 Was immunogenic in Young Adults hsba Responses to MnB Bearing Diverse fhbp Variants (US Study 1004, subjects 18 to 25 Years of Age) Responder Rate (%) % of subjects with hsba titer > 1: Predose 1 Postdose PMB2707 PMB1590 PMB1489 PMB1256 PMB1745 PMB1321 PMB2948 PMB3302 PMB2001 * * * * * * * B44 B16 B09 B03 A05 A22 B24 A04 A56 Data generated using sera from a subset of subjects (n~ 20) * MnB strains expressing fhbp/lp2086 variant heterologous to vaccine antigen Jansen MRF Conference 2011

17 Bivalent rlp2086 Investigational Vaccine Induces hsba Responses in Adolescents and Young Adults Subfamily B B44 B02 B107 B10 B08 B09 B07 B05 B01 B52 B13 B15 B03 B16 B24 A62 Strains expressing vaccine homologous LP2086 variants Strains expressing vaccine heterologous LP2086 variants POC and exploratory strains A Genetic Distance A04 A63 A28 A05 A56 A06 A29 A42 A76 A02 A01 A08 A07 A20 A17 A19 A15 A12 A10 A26 Subfamily A 17

18 Bivalent rlp2086 Phase 2/3 Vaccine Clinical Development Plan (Ongoing and Planned Clinical Studies) STUDY DESCRIPTION Adolescent Safety & Immunogenicity Safety & Immunogenicity 2-dose schedules Safety & Immunogenicity Concomitant Repevax Safety & Immunogenicity & Concomitant Menactra/Adacel Safety & Immunogenicity & Concomitant Gardasil Large Scale Safety Study Young Adult Safety & Immunogenicity Lot Consistency & Pivotal Immunogenicity Study Population Adolescents Adolescents Adolescents Adolescents Adolescents Adolescents + Young adults Young adults Adolescents 18

19 Summary Pfizer s investigational MnB vaccine is based on LP2086, a surface-exposed factor H binding protein (fhbp), important for survival of the organism in vivo Demonstrated hsba activity against >160 epidemiologically relevant invasive MnB strains provides evidence for killing across the diversity of variants within the two fhbp subfamilies Phase 1 and 2 clinical studies in adolescents and young adults have shown that the bivalent rlp2086 investigational vaccine has an acceptable safety profile elicits a response that is broadly active against diverse MnB strains A comprehensive clinical development program is ongoing to support licensure in adolescents and young adults to protect against invasive MnB disease

20 Acknowledgements Clinical Investigators P. Richmond, University of Western Australia School of Paediatrics and Child Health, Australia M. Nissen, Royal Children's Hospital and Children s Health Service District, Australia H. Marshall, Women s and Children s Hospital and University of Adelaide, Australia M. Garces-Sanchez, C.S. Nazaret, Valencia, Spain F. Martinon-Torres, Hospital Clínico Universitario de Santiago de Compostela, Spain National Public Health Laboratories P. Kriz, M. Musilek, J. Kalmusova, National Institute of Public Health, Prague, Czech Rep. M-K. Taha, A-E. Deghmane, Institut Pasteur, Paris, France D. Martin, Institute of Environmental Science and Research, Porirua, New Zealand D. Caugant, T. Alvestad, Norwegian Institute of Public Health, Oslo, Norway A. von Gottberg, M. du Plessis, K. Klugman, National Institute for Communicable Diseases, Johannesburg, South Africa L. Mayer, X. Wang, Centers for Disease Control, Atlanta, Georgia, USA R. Borrow, J. Findlow, Health Protection Agency, Manchester, UK U. Vogel, M. Frosch, Institut for Hygiene, University of Wuerzburg, Germany J. Vazquez, Reference Laboratory for Meningococci, Instituto de Salud Carlos III, Madrid, Spain Pfizer Colleagues A. Anderson, T. Jones, S. Harris, S. Hoiseth, E. Murphy, L. McNeil, L. K. Jansen, E. Emini J. Eiden, J L. Perez, J. Beeslaar, Ann Wouters, D. Giorgio, W. Gruber, D. Morgenstern N. Tatsis, B. Abbott 20

21 % of Subjects with the Induration rlp2086 Was Well Tolerated in Adolescents Reported Injection Site Induration, B Severity of Induration Within 1-7 days severe moderate mild /196 a 8/192 1/193 4/189 2/168 1/ mcg Placebo 200 mcg 120 mcg 60 mcg Placebo 200 mcg 120 mcg 200 mcg 120 mcg 60 mcg Placebo Dose 1 Dose 2 Dose 3 a number of severe reactions/number of immunizations at dose level 21 Richmond et al 2011

22 Significant MnB Disease Burden in Adolescents and Young Adults (EU, average number of cases ) Average Number of Cases <1 yr 1-4 yrs 5-9 yrs yrs yrs yrs >25 yrs data,