Pfizer: Sharing our Vision for Adult Vaccines Kathrin U. Jansen, PhD Senior Vice President & Head of Vaccine Research & Development, Pfizer Immunization of the Elderly (WHO) Geneva, 22-23 March 2017

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Ageing in the 21st Century

• Reductions of mortality in all ages have added extra years of life to individuals globally

• Increasing life spans likely continue, but gains may be offset unless accompanied by increasing good health

• Ageing individuals and societies demand a comprehensive, systematic methodology to achieve longer/healthier lives

• Such programs must and will include vaccines for the elderly

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Pfizer’s Vision: Vaccines to Protect Against Infectious Disease and Cancer

Group B Streptococcus

(GBS)

Respiratory Syncytial Virus

(RSV)

Cytomegalo virus (CMV)

Vaccine based immunotherapy

and Oncolytic virus

platforms

to address high unmet need tumor types

Prevnar 13

NextGen Prevnar

Staphylococcus aureus

Clostridium

difficile

Group B Streptococcus

RSV

Nimenrix (Meningococcal

A, C, Y, W conjugate)

Trumenba

(Meningococcal B)

Prevnar 13 (Pneumococcal

conjugate)

Broadly protective influenza

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CAPiTA Trial Design and Timeline

R: Randomization; VT: Vaccine-Type; CAP: Community-Acquired Pneumonia. Hak E, Grobbee DE, Sanders EAM, et al. Netherlands J Med. 2008;66:378-383 CAPiTA: Community Acquired Pneumonia immunization Trial in Adults Bonten M et al, (2015) NEJM 372, 1114-25

Sept 2008 Jan 2010 Sept 2011 Aug 2013 2014 20

Regulatory Review of Primary and

Secondary Outcome Data

Interim Analysis

Reached Required Number of Confirmed

VT-CAP Cases

Accrual of VT-CAP Cases

R

Placebo

PCV13

Screening and Recruitment

84,496 Volunteers

≥ 65 years of age

US/EU filings

2015

SSUAD

US/EU approvals/re-

commendations

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CAPiTA Outcome Primary and Secondary Objectives: Per Protocol Population

*95% Confidence Interval. Bonten et al 2015 NEJM 372:12 CAPiTA: Community Acquired Pneumonia Immunization trial in Adults

Efficacy Endpoint

Vaccine Group

VE (%) 95.2% CI p-Value PCV13

(n=42,240) Placebo

(n=42,256) First Episode of Confirmed VT Pneumococcal CAP 49 90 45.6 (21.8,62.5) <0.001

First Episode of Confirmed NB/NI VT Pneumococcal CAP 33 60 45.0 (14.2, 65.3) 0.007

First Episode of VT-IPD 7 28 75.0 (41.4, 90.8)* <0.001

Vaccine-Type CAP NB and NI CAP Vaccine-Type IPD

Post Hoc Analysis of the Cumulative Episodes of the Primary and Secondary Efficacy End Points in the Per Protocol Population

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Incidence of US CAP (Hospitalized Adults 65 Years and Older)

(P) Represents a prospective cohort/surveillance study. Ramirez J, Wiemken T, et al. Risk for Hospitalization Due to Community-Acquired Pneumonia (CAP) in Non-Elderly Patients with Comorbid Conditions: The Louisville Pneumonia Study. Poster 044. ISPPD-10. Glasgow, UK. Jun 2016.

Time

1,014 1,150

1,230

1,796

1,997

1,643

1,375

897

2,327

0

500

1,000

1,500

2,000

2,500

Marston et al.1991(P)

Jackson et al.1998-2001

Nelson et al.1998-2004

Yu et al.2007-2008

Griffin et al.2007-2009

Shea et al.2006-2010

Simonsen et al.2011-2012

Jain et al.2010-2012

(P)

Ramirez et al.2014-2015

(P)

(P) Represents a prospective cohort/surveillance study. 20

14 C

DC

65+

1.7x

Annual Incidence of Hospitalized CAP per 100,000 in Adults 65+

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Invasive Pneumococcal Disease in US Adults ≥65 Years of Age

*PPSV23 serotypes: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, AND 33F *PCV13 serotype: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, AND 23F Active Bacterial Core surveillance data, 1998-2015, unpublished

Trends in Invasive Pneumococcal Disease Among Adults Aged >65 Years Old, 1998-2015

59 60 58

51

43 42 38 36

40 39 41 39 36 35

29 31

25 26

51 50 49

42

34 32 27 26 27 26 27 26

23 22 18 18

13 15

44 46 43

36

29

23 20 18 17 17 18 17

14 11 9 7 5 6

0

10

20

30

40

50

60

70

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Cas

es P

er 1

00,0

00

Year

All IPD PPSV23 Type PCV13 Type

PCV7 Introduction

PCV7 Introduction for Children

PCV13 Recommendations for Immunocompromised Adults 19+

PCV13 Recommendations for Adults 65+

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S. aureus Disease Has Diverse Manifestations and Affects Many Patient Populations (US Data Only)

SA=S. aureus; MRSA=methicillin-resistant Staphylococcus aureus; MSSA=methicillin-sensitive Staphylococcus aureus. 1. Foster T. Staphylococcus. In: Baron S, ed. Medical Microbiology. Galveston, TX: University of Texas Medical Branch at Galveston; 1996. 2. Liu C et al. Clin Infect Dis 2011;52:285-292. 3. Cunha BA. Clin Microbiol Infect 2005;11(suppl 4):33-42. 4. Yu H et al. ICAAC 2012. September 9-12, 2012. San Francisco, CA. Presentation K259. 5. Styers D et al. Ann Clin Micro Antimicrob 2006;5:2. 6. Kuehnert MJ et al. J Infect Dis 2006;193:172-179. 7. von Eiff C et al. N Engl J Med. 2001;344:11-16. 8. Hersh AL et al. Arch Intern Med. 2008;168:1585–1591. 9. Centers for Disease Control and Prevention. MRSA and the workplace [updated 19 September 2014]. Available from: http://www.cdc.gov/niosh/topics/mrsa/. 10. Laupland KB et al. J Infect Dis. 2003;187:1452-1459. 11. Dancer SJ. Lancet Infect Dis. 2008;8(2):101-113. 12. National Nosocomial Infections Surveillance System. Am J Infect Control 1996;24(5):380-388.13. Eili Klein*, David L. Smith†, and Ramanan Laxminarayan. Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999–2005. Volume 13, Number 12—December 2007 Research. 14 Koeck et al, Invasive Staphylococcus aureus Infections in Minnesota: A Large Role for MSSA. IDWeek 2015. 15. CDC. 2014. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Methicillin-Resistant Staphylococcus aureus, 2014. Available via the Internet: http://www.cdc.gov/abcs/reports-findings/survreports/mrsa14.htmll.16. CDC data (Scott Fridkin/CDC) (June 7, 2016) 17 http://www.cdc.gov/nchs/fastats/inpatient-surgery.htm (removed diagnostic procedures and percutaneous procedures as possible, e.g., endoscopy and cardiac catheritization)

Disease severity

Size of affected population

• 190,000 invasive SA infections in the US annually14, 15

• 260,000 SA wound infections annually16

• 180 SA SSI per 100,000 NHSN surgical procedures16

• 20,000 deaths due to S. aureus in the US annually13

• 32 M surgeries in the US annually17

Skin and Soft Tissue Infection (SSTI) Carbuncle, impetigo, cellulitis, wound/burn

infection, abscess, SSI1,2,12

Carriage/Colonization Anterior nares, oropharynx, GI, skin, vagina10

Metastatic Infection

Endocarditis, osteomyelitis,

device- related1,2

Deep Infection Surgical site infection (SSI)

Arthritis, mediastinitis, osteomyelitis, Device-related pneumonia1,2,12

Bloodstream Infection (BSI)

• Hemodialysis patients9

• Nursing home residents8

• 9.6 million abscess or cellulitis cases diagnosed in ambulatory settings in US (2005)7

• ~30% adults colonized5

• ~82% bacteremia due to colonizing strain6

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S. Aureus: Design of SA4Ag Vaccine Trial (Phase 2)

Frenck, R., et al 2014. Open Forum Infectious Diseases. 1(S1) 600. Proceedings from ID Week (Joint meeting of IDSA, SHEA, HIVMA and PIDS), Philadelphia, PA, Oct 8-12, 2014

• Subjects had a mean age of 45.0 years, 56.8% were female, and 73.2% were white

• 87.5% of subjects completed the study through Month 12 R

ando

miz

atio

n

456 Participants Enrolled at 13 US Sites

18 to 49 Years (n=233)

50 to 64 Years (n=223)

Low-dose rP305A (n=117)

Mid-dose rP305A (n=114)

High-dose rP305A (n=113)

Placebo (n=112)

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Safety Summary

AE, adverse event Frenck, R., et al 2014. Open Forum Infectious Diseases. 1(S1) 600. Proceedings from ID Week (Joint meeting of IDSA, SHEA, HIVMA and PIDS), Philadelphia, PA, Oct 8-12, 2014

Local Reactions Reported Through Day 14

• Local reactions generally were mild or moderate in severity

• Systemic events and other AEs were comparable across SA4Ag and placebo groups

• No vaccine-related serious AEs or deaths were reported

0

10

20

30

40

Injection SitePain

Swelling Redness

Perc

enta

ge o

f Sub

ject

s R

epor

ting

Placebo (n=112)Low-dose rP305A (n=116)Mid-dose rP305A (n=114)High-dose rP305A (n=112)

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SA4Ag Elicited Immune Responses Rise Rapidly and Are Sustained Through Month 12

Frenck, R., et al 2014. Open Forum Infectious Diseases. 1(S1) 600. Proceedings from ID Week (Joint meeting of IDSA, SHEA, HIVMA and PIDS), Philadelphia, PA, Oct 8-12, 2014

Low-dose Mid-dose High-dose Placebo

CP8 (OPA) CP5 (OPA)

P305A (cLIA) CIfA (cLIA)

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SA4Ag Immune Responses Are Not Dramatically Affected by Age

Frenck, R., et al 2014. Open Forum Infectious Diseases. 1(S1) 600. Proceedings from ID Week (Joint meeting of IDSA, SHEA, HIVMA and PIDS), Philadelphia, PA, Oct 8-12, 2014

CP5 (OPA)

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Clostridium Difficile: A Significant Unmet Medical Need in Older Adults

Bacteria express toxins causing severe diarrhea

C. difficile at “Hazard Level – Urgent” (CDC)

>450,000 cases and >29,000 deaths/year

in US

Antibiotic use causes C. difficile infection

Currently There is No Vaccine to Prevent Initial or Recurrent Infections

1. Lucado J, et al. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006–2012 Jan. 2. Giannasca PJ, et al. Infect Immun. 1999;67(2):527-538. 3. Torres JF, et al. Infect Immun. 1995;63(12):4619-4627. 4. Lessa FC, et al. N Engl J Med. 2015;372:825.

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Robust C. Difficile Toxin Neutralizing Immune Response Observed with Genetically Detoxified Toxoids (Phase 1, Evaluable Immunogenicity Population)

Sheldon et al Vaccine 2016:34:2082-91

Toxin B-Specific Neutralizing Antibody GMC (65- to 85-Year Age Cohort)

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Complex Barriers to Adult Vaccination • Some vaccines are universally recommended for adults, while others

are recommended for certain age groups, targeted to individuals with specific risk factors or targeted to particular combinations of age and risk factors

Low level of patient awareness

Lack of available public health information

Lack of adult disease and vaccine surveillance

Lack of medical/scientific recommendation

Low level of government support for adult prevention and vaccines

Lack of reimbursement or willingness to vaccinate adults

Lack of adult vaccine administration settings/schedules

Low level of healthcare provider awareness of vaccine benefits