Pfizer’s Investigational Vaccine, rLP2086, for

Invasive Meningococcal Serogroup B Disease

1

Laura J York, PhD

Sr Director, International Scientific & Medical Affairs

Serogroup B is now the predominant remaining meningococcal serogroup in several parts of the world

Note: *Number of cases is an average of 2002-2005. Isolates were collected from 19 countries and the Caribbean Epidemiological Center. Most isolates were

from Brazil and Chile.

Source:14 EU-IBIS (2006); 24CDC (2010) MMWR 57(54); 25CDC ABCs Reports; 26Public Health Agency of CA (2009) CCDR; 27Chiou, CS. et al. (2006) BMC

Infect Dis; 8Harrison, LH et al. (2009) Vaccine; 28WHO, Africa (2009); 29AU Government Department of Health and Aging (2009); 30NZ Ministry of Health (2008).

United States

200825, 26

n = 1,172

B

(35%)

C

(31%)

Y

(25%)

Other

(9%) Canada26

2006

n = 210

B

(54%)

Y

(13%)

C

(20%)

Other

(13%)

Y

(2%)

W135

(2%)

Latin America and the Caribbean*8

2005

n = 1,391

African Meningitis Belt28

2006

n = 2,192

A

(91 %)

W135

(8%)

Other

(1%)

B

(76%)

C

(17%)

Y

(3%)

Other

(4%)

European Union14

2006

n = 5,223 Taiwan27, 8

2001

n = 43

C

(3%)

Australia29

2007

n = 304

New Zealand 30

2007

n = 105

B

(84%)

Other

(9%) C

(8%)

C

(11%)

Other

(6%)

B

(83%)

C

(26%)

B

(69%)

Y

(11%)

A

(2%) Other

(1%)

W135

(31%) B

(52%)

Age-specific Incidence of Serogroup B Meningococcal Disease in the EU

EU

EU-IBIS Invasive N.Menigitidis in Europe Reports; www.euibis.org

Significant MnB Disease Burden in Adolescents and Young Adults (EU, average number of cases 1999 – 2006)

0

100

200

300

400

500

600

700

800

<1 yr 1- 4 yrs 5- 9 yrs 10 -24 yrs 25 - 44 yrs 45 - 64 yrs 65+ yrs

Num

ber

of

Cases

EU-IBIS Invasive N.Menigitidis in Europe Reports; www.euibis.org

Meningococcal Carriage Rates Are Highest in Adolescents

Pre

vale

nce (

%)

Age (Years)

Modified from Christensen et al. (2010). Lancet Infect. Dis. 10: 853-861

Vaccination of adolescents has the

potential to provide direct and

indirect (herd immunity) benefits

5

Serum Bactericidal Screen Was Used to Identify Pfizer’s MnB Vaccine Candidate

Fletcher et al. 2004; Bernfield et al 2002

Important Target Antigen Attributes

Surface exposed

Highly conserved

Expressed universally in diverse strains

Induces serum bactericidal activity

N. meningitidis

Serogroup B

Extract and

Fractionate

Immunize

Mice

hSBA Screen Against

Diverse MnB

1 2 3 4 5 6

6

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 2009

7

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

8

0.05

Subfamily A

B24

B16

B01

B44 B02

B03

B05

B07 B09

B10 B13 B15

A05

A06

A29 A01

A02

A22

A19 A17

A07

A12

A26

A15

A20

A10

A09

A04

0.05 0.05

Subfamily B B24

B16

B01

B44 B02

B03

B05

B07 B09

B10 B13 B15

A05

A06

A29 A01

A02

A22

A19 A17

A07

A12

A26

A15

A20

A10

A09

A04

Murphy et al. 2009; Jiang et al. 2010

Broad Protection Against Diverse, Invasive MnB Strains Requires an LP2086 Protein From Both Subfamilies

Vaccine: rLP2086A rLP2086B

LP2086 Subfamily A

Expressing SBA Strains

A05* A07 A17 A19 A22

1

10

100

1000

10000

100000

LP2086 Subfamily B

Expressing SBA Strains

B01* B02 B09

B16 B24

hS

BA

GM

T T

iter

rLP2086A and rLP2086B

Jiang et al. 2010

*Vaccine homologous LP2086 Variants

0.05

Genetic Distance

B24

B16

B01

B09

A05

A22

A19 A17

A07

71%

Subfamily B

29%

Subfamily A

McNeil et al. 2009; Jiang et al. 2010

B02

A06

A29 A01

A02

A76

A04

A28

A42

A56

A63 A12

A26

A15

A20

A10 A08

A62

B107

B05 B07

B03

B10 B13

B15 B08

B52

B44

Pfizer’s Bivalent rLP2086 Investigational Vaccine Elicits Broad hSBA Activity

Strains killed expressing

vaccine homologous LP2086

variants

Strains killed expressing

vaccine heterologous LP2086

variants

10

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

Phase 2 MnB Vaccine Study in Adolescents (B1971005) 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

12

Richmond et al 2011

Percentage of Adolescents Reporting Fever (B1971005)

Severity of Fever Within 1-7 days

0

10

20

30

40

50

60

70

80

90

100

Place

bo

60 m

cg

120 m

cg

200 m

cg

Place

bo

60 m

cg

120 m

cg

200 m

cg

Place

bo

60 m

cg

120 m

cg

200 m

cg

Dose 1 Dose 2 Dose 3

% o

f S

ub

jects

wit

h t

he F

ever

39.0 - 40.0

38.5 - 38.9

38.0 - 38.4

2/193 1/197a 2/192 1/189 2/155 1/118 1/102

a number of severe reactions/number of immunizations at dose level

No fever >40.0C

13

Richmond et al 2011

rLP2086 Was Immunogenic in Adolescents hSBA Responses to MnB Bearing Diverse fHBP Variants,

Dose Selection for Completion of Clinical Program (B1971005)

Control 120 µg dose (0, 2 6 months)

% hSBA ≥ 1:4

SBA Test

Strain PD3 PD2 PD3

A05 11.8

(6.3, 21.2)

89.0

(81.9, 93.5)

97.4

(92.2, 99.1)

A04* 16.1

(8.6, 28.1)

100

(93.5, 100.0)

100

(93.1, 100.0)

A56* 15.4

(8.2, 25.3)

94.9

(89.2, 98.1)

98.2

(93.8, 99.8)

B02* 6.3

(2.7, 14.3)

79.5

(71.4, 85.8)

92.0

(85.4, 95.8)

B03* 8.8

(4.0, 18.3)

33.3

(24.9, 43.0)

75.6

(65.1, 83.3)

B44* 6

(2.0, 13.5)

70.4

(61.2, 78.6)

88.7

(81.4, 93.8)

14

Richmond et al 2011

* MnB strains expressing fHBP/LP2086 variant heterologous to vaccine antigen

rLP2086 Was immunogenic in Adolescents hSBA Responses to MnB Bearing Diverse fHBP Variants (US Study 2001, subjects 11 to 18 Years of Age)

* MnB strains expressing fHBP/LP2086 variant heterologous to vaccine antigen

15

0

20

40

60

80

100

PMB2707 PMB1256 PMB1745 PMB1321 PMB2948 PMB17 PMB3302 PMB2001

B44 B03 A05 A22 B24 B02 A04 A56

Res

po

nd

er

Rate

(%

)

Predose 1

Postdose 3

* * * * * * *

% of subjects with hSBA titer > 1:4

Jansen MRF Conference 2011

rLP2086 Was immunogenic in Young Adults hSBA Responses to MnB Bearing Diverse fHBP Variants

(US Study 1004, subjects 18 to 25 Years of Age)

0

10

20

30

40

50

60

70

80

90

100

PMB2707 PMB1590 PMB1489 PMB1256 PMB1745 PMB1321 PMB2948 PMB3302 PMB2001

B44 B16 B09 B03 A05 A22 B24 A04 A56

Res

po

nd

er

Rate

(%

)

Predose 1

Postdose 3

Data generated using sera from a subset of subjects (n~ 20)

* MnB strains expressing fHBP/LP2086 variant heterologous to vaccine antigen

% of subjects with hSBA titer > 1:4

Jansen MRF Conference 2011

* * * * * * *

Bivalent rLP2086 Investigational Vaccine Induces hSBA Responses in Adolescents and Young Adults

0.05

Genetic Distance

B24

B16

B01

B09

A05

A22

A19 A17

A07

Subfamily B

Subfamily A

B02

A06

A29 A01

A02

A76

A04

A28

A42

A56

A63

A12

A26

A15

A20

A10 A08

A62

B107

B05 B07

B03

B10 B13

B15 B08

B52

B44

Strains expressing

vaccine homologous LP2086

variants

Strains expressing

vaccine heterologous LP2086

variants

POC and exploratory strains

17

Bivalent rLP2086 Phase 2/3 Vaccine Clinical Development Plan (Ongoing and Planned Clinical Studies)

STUDY DESCRIPTION Study Population

Adolescent Safety & Immunogenicity Adolescents

Safety & Immunogenicity 2-dose schedules Adolescents

Safety & Immunogenicity Concomitant Repevax Adolescents

Safety & Immunogenicity & Concomitant Menactra/Adacel Adolescents

Safety & Immunogenicity & Concomitant Gardasil Adolescents

Large Scale Safety Study Adolescents + Young

adults

Young Adult Safety & Immunogenicity Young adults

Lot Consistency & Pivotal Immunogenicity Adolescents

18

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

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

rLP2086 Was Well Tolerated in Adolescents Reported Injection Site Induration, B1971005

Severity of Induration Within 1-7 days

0

10

20

30

40

50

60

70

80

90

100

Place

bo

60 m

cg

120 m

cg

200 m

cg

Place

bo

60 m

cg

120 m

cg

200 m

cg

Place

bo

60 m

cg

120 m

cg

200 m

cg

Dose 1 Dose 2 Dose 3

% o

f S

ub

jec

ts w

ith

th

e In

du

rati

on

severe

moderate

mild

1/193 1/196a 8/192

4/189 2/168 1/155

a number of severe reactions/number of immunizations at dose level

21

Richmond et al 2011

Significant MnB Disease Burden in Adolescents and Young Adults (EU, average number of cases 1999 – 2006)

www.euibis.org data, 1999-2006

0

100

200

300

400

500

600

700

800

<1 yr 1- 4 yrs 5- 9 yrs 10 -14 yrs 15 - 19 yrs 20 - 24 yrs >25 yrs

Av

era

ge

Nu

mb

er

of

Ca

se

s