wyeth 2006 Analysts Meeting Presentation

Welcome

Justin R. VictoriaVice President, Investor Relations

Forward Looking StatementThe statements in these materials that are not historical facts are forward-looking statements based on current expectations of future events and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include risks associated with the inherent uncertainty of the timing and success of product research, development and commercialization (including with respect to our pipeline products), drug pricing and payment for our products by government and third-party payers, manufacturing, data generated on the safety and efficacy of our products, economic conditions including interest and currency exchange rate fluctuations, changes in generally accepted accounting principles, the impact of competitive or generic products, trade buying patterns, global business operations, product liability and other types of litigation, the impact of legislation and regulatory compliance, intellectual property rights including the ability of any particular patent to provide market exclusivity, strategic relationships with third parties, environmental liabilities, and other risks and uncertainties, including those detailed from time to time in our periodic reports filed with the Securities and Exchange Commission, including our current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption “Item 1A, Risk Factors.” We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

AgendaWelcome J. Victoria

Introduction R. Essner

Enbrel® & Prevnar® U. WiinbergPrevnar 13 E.A. Emini, Ph.D.

Break

Mid-Pipeline Review R.R. Ruffolo, Jr., Ph.D.Key Registration Submissions

Conclusion & Q&A B. Poussot

New Products J.M. Mahady Pristiq™ G. Constantine, M.D.Aprela™/Viviant™Lybrel™Torisel™ J.S. Camardo, M.D.Tygacil®Bifeprunox R.M. Poole, M.D., FACPMethylnaltrexone J.S. Camardo, M.D.

Introduction

Robert EssnerChairman and Chief Executive Officer, Wyeth

Revenue Growth

Wyeth Past Business Performance

$18.8$18.8$17.4$17.4$15.9$15.9

$14.6$14.6$14.0$14.0

$0

$5

$10

$15

$20

2001 2002 2003 2004 2005

(In B

illio

ns) +9% +10% +8%

+4%+7%

WHIImpact

Wyeth Past Business Performance

* Before Certain Significant Items

$2.92$2.92$2.62$2.62

$2.44$2.44$2.22$2.22$2.18$2.18

$0.00

$0.50

$1.00

$1.50

$2.00

$2.50

$3.00

2001 2002 2003 2004 2005

+10% +7%+11%

EPS* Growth

+2%+15%

WHIImpact

EPS Continues to Grow in 2006

$0.00

$0.50

$1.00

$1.50

$2.00

$2.50

$3.00

2001 2002 2003 2004 2005 2006

+10% +7%+11%

EPS* Growth

+2%+15%$3.07+

+12%+

JulyGuidance

**

WHIImpact

* Before Certain Significant Items** When Adjusted for Stock Option Expensing in 2005

7 New Drugs11 Important Indications

Pristiq™ Major Depressive DisorderVasomotor Symptoms

Pristiq™ Major Depressive DisorderVasomotor Symptoms

Viviant™ Prevention/Treatment OsteoporosisViviant™ Prevention/Treatment Osteoporosis

Aprela™ Menopausal Symptoms/OsteoporosisAprela™ Menopausal Symptoms/Osteoporosis

Lybrel™ ContraceptionLybrel™ Contraception

Torisel™ Renal Cell CancerMantle Cell Lymphoma

Torisel™ Renal Cell CancerMantle Cell Lymphoma

Bifeprunox SchizophreniaBifeprunox Schizophrenia

Methylnaltrexone SC – Opioid Induced ConstipationIV – Post Operative Ileus

Methylnaltrexone SC – Opioid Induced ConstipationIV – Post Operative Ileus

Tygacil®* CAP/HAPTygacil®* CAP/HAP

* Tygacil already approved, not a new drug

Wyeth Future Growth Prospects

In-Line Product Growth

Portfolio of New Product Opportunities

Productivity Improvements

Broad-Based Research

Wyeth is positioned to bea stronger company

at the end of the decadeand enter the next decade with

great momentum.

Enbrel®(Etanercept)

Ulf WiinbergSenior Vice President, Wyeth

President, Wyeth Pharmaceuticals - EMEA

Enbrel® 2005Over 376,000 Patients Treated Worldwide

North America*$2,574

North America*$2,574

EMEA$958EMEA$958

Latin America$46

Latin America$46

Asia Pac$79

Asia Pac$79

$3,6582005 Worldwide Sales

$3,6582005 Worldwide Sales

*Alliance with Amgen

$ in Millions

Enbrel® Reaches Top 10 Worldwide

ProductMAT 6/06

RankMAT 6/06

Sales ($000)

Change vs. Prior Period

($000)

% Change vs. Prior Period

LIPITOR 1 13,306,463$ 593,102$ 5%PLAVIX 2 6,353,507$ 787,322$ 14%NEXIUM 3 6,193,180$ 903,461$ 17%SERETIDE 4 5,910,049$ 681,602$ 13%ZOCOR 5 5,463,607$ (221,986)$ -4%NORVASC 6 4,940,892$ 58,022$ 1%ZYPREXA 7 4,620,598$ (204,740)$ -4%ARANESP 8 4,270,374$ 1,093,301$ 34%RISPERDAL 9 4,253,853$ 447,044$ 12%ENBREL 10 4,142,088$ 845,371$ 26%

Enbrel® Momentum

*Japan Launch March 2005

59%$1,083Total Regional Net Sales

295%$79AP/Japan*

64%$46Latin America

52%$958EMEA

% Growth2005 Actual

($ in Millions)Region

Enbrel®Growing From a Position of Strength

$0

$50,000

$100,000

$150,000

$200,000

$250,000

$300,000

$350,000

$400,000

Q1'04 Q2'04 Q3'04 Q4'04 Q1'05 Q2'05 Q3'05 Q4'05 Q1'06 Q2'06

Enbrel Remicade Humira Orencia Raptiva

Anti-TNF Biologic Sales – Ex-North America ($000)

Quarterly Sales

IMS, Midas Q2 2006

Enbrel® -- $3 Billion in 2010Outside North America

Market Factors

Large available patient pool

Doctors & payers inclined to early intervention with Enbrel

Enbrel

Geographic and medical expansion

Unique mechanism of action with extensive safety/efficacy

Patent protection through 2014

Available Patient Pool: Top 6 EU Countries

Prevalence of Disease

Guidelines for EligibilityGuidelines for Eligibility

Current Biologic PatientsCurrent Biologic Patients

1.8 Million1.8 Million 1.3 Million1.3 Million 6.0 Million6.0 Million826,000RARA ASAS PsA PsOPsO

360,000 Patients

SOURCE: Wyeth Forecasting; C&MINOTE: Slide depicts RA, PsA, AS and Psoriasis

Japan Opportunity

28

110

13 4

49

6

0

20

40

60

80

100

120

140

Bio-Potential (M) Biologics(M) Enbrel(M)

Incremental Opportunity

# Patients (2005)

Japan1 in 10 Currently Treated

~60,000

Num

ber

of P

atie

nts

(000

’s)

Enbrel® Science14 Years Experience

#1 biologic prescribed worldwide in its class

Approaching 1 million patient years of use

Studied in patients 4 to 87 years of age

Serious adverse event profile similar to placeboin clinical trials

Unique mechanism of action

Enbrel® Science14 Years of Clinical Experience

55%

64%

73%

5 Years

n = 100

NO further joint space narrowingNO further joint space narrowing

NO new erosionsNO new erosions

NO progression inTotal Sharp ScoreNO progression inTotal Sharp Score

Percentage of Early RA Patients With No Radiographic Progression

SustainedEfficacy

After 5 years

Genovese MC, Bathon JM, Fleischmann RM, et al. Longterm safety, efficacy, and radiographic outcome with etanercepttreatment in patients with early rheumatoid arthritis. J Rheumotol 2005;32:1232-1242.

Trend Towards Earlier Treatment

Recent-Onset RA

Severely-Advanced RA

Moderately-Advanced

RA

Value: Favorable Cost-BenefitNICE Guidance 2006

The National Institute for Health and Clinical Excellence (NICE, UK) recommends the use of ENBREL® for the treatment of plaque psoriasis BEFORE the use of Raptiva

ENBREL had a more favorable economic profile in the treatment of patients with psoriatic arthritis than Remicade

Convenience

Pre-filled Syringe 25mg/50mg

Autoinjector

Patient Services

The flexibility of 3 administration options

NEW!NEW!

2005 $1 Billion

2010 $3 Billion

Enbrel® Growth-2010Wyeth-Only Territories – 24% CAGR

Europe$958

Europe$958

Europe80%

Europe80%

LatinAmerica

$46 LatinAmerica

5%

AsiaPacific15%

AsiaPacific

$79

% of Revenue by Region $ in Millions

Grange Castle … Wyeth’s Commitment to Biotech Growth

4 Integrated Manufacturing Facilities

Drug Substance

Vaccine Conjugation

Fill / Finish

Syringe Line MNTX

Prevnar®Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)

Prevnar® – Strong Growth Momentum

+33%$950 millionTOTAL

+41%$55 millionAsia Pacific

+70%$45 millionLatin America

+94%$285 millionEMEA

+13%$565 millionNorth America

ΔΔ vs 1H05vs 1H05June 2006 YTDJune 2006 YTDRegionRegion

$0

$200

$400

$600

$800

$1,000

$1,200

Aud

ited

Ann

ual S

ales

($M

M)

Global Vaccine Sales by Product2005 Audited Sales

Varivax

Engerix B

MMRII

Vaxigrip

1st and Only Blockbuster Vaccine

Combinedaudited salesof these four vaccine productsdoes not equal Prevnar’s sales

Source: IMS MIDAS Data, ATC2-J7, April 2006.

Prevnar®

Growing Prevnar® to $3 Billion in 2010Accelerating momentum in 2006New launchesNew national immunization programs in developed marketsEmerging countries – private and national programsIncreased compliance and catch-up opportunities

$3 Billion Prevnar Sales(Infant Vaccination)

Bacteremia

Pneumonia

Otitis Media

Meningitis

Major Pneumococcal Diseases

Adults dieevery yearAdults dieevery year

.5M.5M

The Face ofPneumococcal Disease

1MInfants dieevery yearInfants dieevery year

#1 Cause ofVaccine-Preventable Death in Children

Hib15%

Rotavirus15%

DTP/Polio20%

Measles21%

Other1%

WHO 2004 Global Immunization Data

S. Pneumo28%

S. Pneumo28%

Disease Burden in Children

Impact onPneumococcal Disease

Tens of millions of children immunized

Millions of cases of disease averted

Tens of thousands of lives saved

…many more children and adults will benefit as we expand the use of Prevnar across the globe

Since the launchof Prevnar ® …

Increasing Impact of Prevnar® in U.S.

MMWR. 2005;Vol: 54(No. 36):893-897.

0

10

20

30

40

50

60

70

80

90

Average for1998 and 1999

2003

Esti

mat

ed C

ases

/10

0,0

00

Prelicensure(1998-1999)

Postlicensure(2003)

94%Reduction

…in children … and adults

0

5

10

15

20

25

30

35

Ave

rag

e In

cid

ence

of

Vac

cin

e S

ero

typ

eIP

D p

er 1

00

,00

0 P

op

ula

tio

n

Prelicensure(1998-1999)

Postlicensure(2002-2003)

55%Reduction

(>50 Years of Age)

Average for1998 and 1999

2003

$3 B +

$1.5 B

$0

$1

$2

$3

$4

2005A 2010F

Sale

s (

$B)

Source: Wyeth internal sales data, 2006

Significant Future Growth Potential

Double sales over the next 5 years

New LaunchesNIPsEmerging MarketsCompliance/Catch-up

New LaunchesNIPsEmerging MarketsCompliance/Catch-up

Prevnar®

Launched in 70 CountriesLaunched in 70 Countries

Additional 13 launchesby 2008

National Immunization Programs:Developed Countries

Current NIPsUnited StatesAustraliaCanadaFranceGermanyGreeceLuxembourgNetherlandsNorwayQatarSwitzerlandUnited Kingdom

AustriaBelgiumDenmarkFinlandHong KongIcelandIrelandItalyJapan

TaiwanNew ZealandPortugalSaudi ArabiaSingaporeSouth KoreaSpainSweden

Potential NIPs

Total Birth Cohort ~7 Million Total Birth Cohort ~4 Million

Emerging Market Opportunities

Private to Potential NIPsChile

China

Ecuador

Hungary

India

Indonesia

Malaysia

Pakistan

* Mexico announced initiation of national program in 3Q06

Peru

Philippines

Romania

Russia

South Africa

Thailand

Uruguay

Argentina

Brazil

Colombia

Czech Republic

Mexico*

Poland

Turkey

Venezuela

Private Markets

Total Birth Cohort ~10 Million Total Birth Cohort ~58 Million

Growth in NIP Countries

Increase compliance with country-recommended regimens (U.S. example)

2002 public/private market compliance ~40%(3 doses or more)

2005 public/private market compliance ~83% (3 doses or more)

Target DTaP “Gold Standard” compliance ~90%

Each compliance % point increase ~$10 million/year

Catch-up opportunities

U.K. program 1.7 million doses in 2006/2007

Growing Prevnar® to $3 Billion in 2010Accelerating momentum in 2006New launchesNew national immunization programs in developed marketsEmerging countries – private and national programsIncreased compliance and catch-up opportunities

$3 Billion Prevnar Sales(Infant Vaccination)

New advances in vaccine development

Potential 10 valent competitive candidate

Prevnar 13 in Phase 3 development

Increase pneumococcal serotype coverage(13 serotypes)

Expand use to adults (> $1.5 billion)

Leading the Way TowardExtended Serotype Coverage With

Pneumococcal 13-Valent Conjugate Vaccine

The Future ofPneumococcal Vaccines:

13-Valent Pneumococcal PolysaccharideConjugate Vaccine

(13v PnC)

Emilio A. Emini, Ph.D., F.A.A.M.Executive Vice President

Vaccine Research and Development

Phase 2 proof of concept achievedLicensing criteria agreed uponWorldwide phase 3 studiesongoingSubmission – Early 2009

Status

> $3 BillionPeak Sales

The most complete vaccine available for the global prevention of pneumococcal diseaseand otitis media

13v PnC Infant Product Profile

7v vs 10v vs 13v Serotype Coverage Comparison – U.S.

Pre-Prevnar® (1998) 81%

7v

Source: CDC ABC Surveillance

13v PnC ProvidesSuperior Coverage in the U.S.

Estimated Invasive Pneumococcal Disease RatesDue to Vaccine Serotypes

(Children <5 Years of Age)

Active Bacterial Core Surveillance, Emerging Infections Program Network. Prevnar® was licensed in the United States in February 2000.

0

1020

30

4050

60

7080

90

Average for 1998 and1999

2003

Esti

mat

ed C

ases

/100

,000 Prelicensure

(1998-1999)

Postlicensure(2003)

94%Reduction

Active Bacterial Core Surveillance, Emerging Infections Program Network. Prevnar® was licensed in the United States in February 2000.

Estimated Invasive Pneumococcal Disease RatesFor All Serotypes


0

20

40

60

80

100

120

Average for 1998 and1999

2003

Esti

mat

ed C

ases

/100

,000 Prelicensure

(1998-1999)

Postlicensure(2003)

75%Reduction


Pre-Prevnar® (1998) 81%

7v

Post-Prevnar (2003) 17%

Prevnar has greatly reduced serious disease caused by the7 vaccine-associated serotypes




10v

81%

7v

Post-Prevnar (2003) 17% 22%

A 10v vaccine provides only marginal additional coverage


Prevnar has greatly reduced serious disease caused by the 7 vaccine-associated serotypes

Pre-Prevnar® (1998)



13v10v

81%

7v

Post-Prevnar (2003) 17% 22% 60%

13v PnC will provide substantial coverage


A 10v vaccine provides only marginal additional coverage

Prevnar has greatly reduced serious disease caused by the7 vaccine-associated serotypes

Pre-Prevnar® (1998)


83%67%63%Norway

70%49%44%France pp

74%59%53%Mexico

83%48%31%Spain pp

81%68%52%Germany pp

13v13v10v10v7v7v

pp = Post-Prevnar®

7v vs 10v vs 13v Serotype Coverage Comparison

13v PnC Also Provides Superior Coverage in Other Countries

33

6A6A

19A19A

13v PnC13v PnC

7F7F

11

55

Serotype Coverage Prevnar® (7v) and 13v PnC

444

1414149V9V9V 18C18C18C

23F23F23F19F19F19F

6B6B6BPrevnarPrevnar

Serotype Coverage Prevnar® (7v) and 13v PnC

444

1414149V9V9V 18C18C18C

23F23F23F19F19F19F

6B6B6BPrevnarPrevnar

GSK 10vGSK 10v33

6A6A

19A19A

13v PnC13v PnC

7F7F

11

55

19A19A

Pai R. JID. 2005;192:1988-95.

Incidence of Invasive Pneumococcal Disease Due to Serotype 19A in the U.S.


0

1

2

3

4

5

6

7

July 1999 –June 2000





Rat

e (C

ases

/10

0,0

00

Pop

ula

tion

)

Time

Comparison of Prevnar® and 13v PnC in a Phase 2 Infant Trial:Percentage of Children Achieving a Protective Level of Functional

Antibody Following the Primary Immunization Series

0

25

50

75

100

4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A

Serotype

7v 13v

Per

cen

tage

The Infant Vaccine Phase 3 Program

Objectives:

Demonstrate the immunological non-inferiority of 13v PnC to 7-valent Prevnar® in young infants

Demonstrate that 13v PnC does not interfere with immune responses elicited by concomitantly administered childhood vaccines

Demonstrate immunological consistency across multiple production batches of the vaccine

Demonstrate the vaccine’s safety and tolerability

The program will involve approximately4,000 children

Proof of concept achieved

Licensing criteria agreed upon

Worldwide phase 3 clinicalstudies to begin in late 2006

Submission 2009

Status

> $1.5 BillionPeak Sales

13v PnC Adult Product Profile

The vaccine of choice for adults 50 yearsof age and older for the prevention of pneumococcal disease

The Need for an Improved Pneumococcal Vaccine for Adults

Current vaccine is a 23-valent free polysaccharide vaccine (23v Ps) indicated for adults 65 years and older

1 Shapiro, et al., NEJM 1991;2 Torling, et al., Vaccine 2003;3 deRoux, et al., IDSA 2005; 4 Jackson, et al., JAMA 1999; Vaccine 2005;5 ACIP recommendation: MMWR 1997.

Therefore, 23v Ps is generally given only once, which provides only a narrow window of protection during a prolonged period of risk5

Effectiveness is very low in immunocompromised patients

Antibody titers and efficacy decline after 5 years1

23v Ps induces immunological hyporesponsiveness to either another dose of 23v Ps2 or to a dose of conjugate vaccine3

Re-vaccinations with 23v Ps cause more severe adverse events4

There Remains a Substantial Invasive Pneumococcal Disease Burden in the U.S.

(2004 Rates With 60% Uptake of 23v Ps Vaccine)

CDC, ABC Surveillance 2004 (provisional)

0

25

50

75

18 to 34 35 to 49 50 to 64 65 to 79 80+

Age Group Years

Cas

es p

er 1

00,0

00 Cases of Invasive Pneumococcal Disease

0

600

1200

1800

18 to 34 35 to 49 50 to 64 65 to 79 80+

Age Group Years

Esti

mat

ed #

of

Dea

ths

Deaths

13v PnC Will Offer Additional Benefits Over 23v Ps Vaccine

Conjugate vaccine antibody responses are superior to 23v Ps antibody responses

Conjugate vaccine does not induce immunological hyporesponsiveness

Therefore, 13v PnC can be used to extend the age range of protection against pneumococcal disease (50 years of age and older) and provide long-term protection by repeat dosing

Immunological Hyporesponsiveness of the 23-Valent Polysaccharide Vaccine

Torling, et.al (2003) Vaccine 22:96-103.

Pre-dose 1 Post-dose 1 1 year Pre-dose 2(4-7 years)

Post-dose 2

Rel

ativ

e A

ntib

ody

Res

pons

e

Immune responsedepressed

after 2nd dose

23v Ps23v Ps

7v7v PnCPnC7v7v PnCPnC

7v7v PnCPnC23v Ps23v Ps

Randomized Trial of 7-valent Prevnar® (7v PnC) and 23v Ps Vaccine in Naïve Elderly 70+ Years of Age

Year 1 Year 2

n = 110

n = 109

n = 43

n = 38

n = 78

23v Ps23v Ps



Year 1 Year 2

Is the Antibody Response to 7v PnC Equivalent/ Superior to the 23v Ps Response?

7v PnC Functional Antibody Response is Equivalent or Superior to 23v Ps Response

0

500

1000

1500

2000

2500

3000

4 6B 9V 14 18C 19F 23F

Serotype

OP

A G

MT

7v PnC 23v Ps*

* *

* Statistically significant

*

7v PnC n = 11023v Ps n = 104-107

23v Ps23v Ps



Year 1 Year 2

Does Prior 23v Ps Immunization Affect the Responseto Subsequent 7v PnC Immunization?

Prior 23v Ps Blunts the Response to Subsequent 7v PnC (Hyporesponsiveness)

0

3

6

9

12

15

18

4 6B 9V 14 18C 19F 23F

Serotype

ELIS

A G

MC

( μg/

ml)

7v PnC 23v PS 7v PnC

*

*

*

***

* Statistically significant

7v PnC n = 6123v Ps 7v PnC n = 62

23v Ps23v Ps



Year 1 Year 2

Does Prior 7v PnC Immunization Blunt the Responseto a Second Dose of 7v PnC?

0

3

6

9

12

15

18

4 6B 9V 14 18C 19F 23FSerotype

ELIS

A G

MC

( μg/

ml) 7v PnC 7v PnC 7v PnC

Prior 7v PnC Does Not Blunt the Response to a Second Dose of 7v PnC

7v PnC n = 6123v Ps 7v PnC n = 31

Does Prior 7v PnC Immunization Affect the Response to Subsequent 23v Ps Immunization?

23v Ps23v Ps



Year 1 Year 2

Prior 7v PnC Does Not Blunt the Response to Subsequent 23v Ps

0

3

6

9

12

15

18

4 6B 9V 14 18C 19F 23F

Serotype

ELIS

A G

MC

( μg

/ml) 23v Ps 7v PnC 23v Ps

23v Ps n = 627v PnC 23v Ps n = 30

Conclusions

Conjugate vaccine can be used repeatedly without inducing hyporesponsiveness

Free polysaccharide vaccine can be administered after conjugate vaccine without hyporesponsiveness

Conjugate vaccine should be given first, if both vaccines are used to maximize serotype coverage

Impact of Extending The Age Range of Protection with 13v PnC

50 yr 65 yr 70 yr

Preventable Invasive Disease Cases

in the U.S.

Deaths Preventable/

Yearin the U.S.

2979

5544

6110

489

895

988

13v PnC + 23v Ps

23v Ps alone

13v PnC alone

Conjugate with re-vaccination

The Adult VaccinePhase 3 Program

Objectives:

Demonstrate immunological non-inferiority of13v PnC to the 23-valent polysaccharide vaccine in vaccine-naïve adults >50 years of age

Demonstrate that 13v PnC can enhance the anti-polysaccharide responses in adults previously immunized with the 23-valent vaccine, and that initial immunization with 13v PnC does not cause immunological hyporesponsiveness

Demonstrate that 13v PnC does not interfere with the immune response to concomitantly administered influenzavirus vaccine

Demonstrate the vaccine’s safety and tolerability

The program will involve approximately 3,200 adults

New Product Opportunities

Joe MahadySenior Vice President, Wyeth

President, Wyeth Pharmaceuticals,The Americas and Global Businesses

Zoloft

Lexapro

Wellbutrin

Paxil

Cymbalta

SNRI Profile Makes Effexor XR®

the #1 Antidepressant in the World

Source: IMS Monthly Midas (Aug 06); Constant US$ (Mil)

Rolling MATs Ending June 2006

$0

$1,000

$2,000

$3,000

$4,000

2001 2002 2003 2004 2005 2006

US

Sale

s D

olla

rs (

000s

)

Pristiq™ (DVS-233)(Desvenlafaxine Succinate)

Pristiq™

Similar to Effexor XR® in terms of efficacy, safety and tolerability

Proven SNRI Pharmacological Impact for Management of Depression

Very low potential for drug-drug interaction

Well-established QTc safety profile

Pristiq™ Differentiation

With FDA-approval, the firstnon-hormonal treatment of moderate-to-severe vasomotor symptoms (VMS)

associated with menopause



0

20,000

40,000

60,000

80,000

100,000

120,000

MAT3/99

MAT3/00

MAT3/01

MAT3/02

MAT3/03

MAT3/04

MAT3/05

MAT3/06

Hor

mon

e P

resc

ript

ions

(00

0)

New Prescriptions

Total Prescriptions

Source: IMS NPA Data (May 06)

Women's Health Initiative: Initial Results Released

WHI Trial Reduced Prescription of Hormone Products

30% Use Estrogen Therapy

Hysterectomized WomenExperiencing Hot Flushes

Menopausal WomenExperiencing Hot Flushes

10% UseHormoneTherapy

Sources: Wyeth /ICR Patient Study Dec 2005, projected to total population using U.S. census data

A Small Percentage of the 23 Million Symptomatic Women Use Available Treatments

15 Million Women 8 Million Women

Pristiq™(Desvenlafaxine Succinate)





Estrogen fluctuation or decline may diminish serotonin and norepinephrine functioning

Transition Through Menopause Can BeAssociated With New Onset or Recurrence

of a Major Depressive Episode

Dual reuptake inhibitor may be a better fit for depression associated with menopause

Female71%

Source: SDI Longitudinal Patient Data, April 2006 (USA)

Women Represent Over 70% of Patients Treated with an Antidepressant

Treated Patients by Gender

Male29%Male29%

Female<40 Years

19%

Female<40 Years

19%

Female>40 Years

52%

Female>40 Years

52%

Initially Approached Two Distinct Products

Depression Vasomotor Symptoms

Product A Product B

PristiqPristiq

Pristiq™, A Single Product WithTwo Indications

First Line Treatment ofMajor Depressive Disorder

Associated With Menopause

Depression

First FDA-ApprovedNon-Hormonal Treatment of

Moderate-to-Severe VMS

Vasomotor Symptoms

Positioning Positioning

Pristiq™

Can become the first and only SNRI proven to effectively address the distinctive symptoms and therapeutic needs of women with:

Depression associated with menopause

Vasomotor symptoms

Fibromyalgia

PristiqPristiq

1 National Institute of Mental Health. “What To Do When A Friend is Depressed…” Bethesda (MD): National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services; 2001.

2 Wyeth /ICR Patient Study Dec 2005, projected to total population using U.S. census data3 Patient Base by Decision Resources, August 2005

2006 Syndicated Depression Omnibus shows VMS and depression overlap of ~3M women, 2005 Depression Consumer Landscape Study shows fibromyalgia and depression overlap of ~1M women

Vasomotor symptoms

23 Million2

Women

U.S. Prevalence

Providing Specific Benefits for Over35 Million Women

Fibromyalgia

4 Million3

Women

Major Depression

12 Million1

Women


Ginger Constantine, M.D.Vice President and Therapeutic Area Director

Woman’s Health and Bone RepairClinical Research & Development,

Wyeth Pharmaceuticals

Pristiq™ Modulates Serotonin and Norepinephrine

Major Depression

Vasomotor Symptoms

Fibromyalgia

Being Developed forFemale Predominant Conditions

May be Integral in Modulation of Depression,Thermoregulatory Dysfunction, Pain

Estrogen: Complex Regulatory Effects onSerotonin and Norepinephrine Pathways

Estrogen influences serotonin and norepinephrine:

Neuronal firing

Release rates

Affects specific receptors

Increases synthesis and decreases breakdown

Norepinephrine stimulation of serotonin neurons may offset estrogen loss

Menopause and Depression Are Linked

0% 20% 40% 60% 80% 100%

Irritability

Depressed Mood

Postmenopause

Premenopause

Maartens LW, et al Fam Pract.;18:189-94,2001.

% Women With Symptom

Risk of Depressive Episode Greater During Perimenopause

Schmidt, et al. Am J Psychiatry. 2004.

0

1

2

3

4

5

6

7

Ris

k of

Dep

ress

ive

Ons

et (%

)

Premenopause Perimenopause

*SSRIs=fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram. †P≤0.05 drug vs. placebo. ‡P≤0.05 vs. SSRIs.Younger women = age ≤40; older women = age >55.Cohen LS, et al. Poster presented at ACNP Annual Meeting; San Juan, Puerto Rico; December 2004.

†

†‡ †‡

0

10

20

30

40

50

(n=263) (n=1041) (n=1007)(n=108) (n=367) (n=355)<40 >55<40 >55 <40 >55

Rem

issi

on R

ate,

Wee

k 8

(%

) Placebo SSRIs* Effexor®/Effexor XR®

P≤0.05

36%

30%

Pooled Analysis of 32 Depression Studies

Remission of Depression: Differential Response With Age

SSRIs and SNRIs

Age


Efficacy on Major Depressive DisordersMen & Women

Pristiq™: Effective in Treating Major Depressive Disorder

Efficacy demonstrated at:

100, 200, and 400 mg in short–term studies

200 and 400 mg in a 6-month relapseprevention study

Pristiq™: Effective in MDD 100 mg - 400 mg/Day

HAM-D Δ from Baseline

0 -3 -6 -9 -12 -15

*

*

*

*

Placebo

Placebo

Pristiq 400 mg

Pristiq 400 mg

Pristiq 200 mg

Pristiq 200 mg

Pristiq 100 mg

Fixed Dose

Study

306

308

* Statistically significant - p <.05 vs placebo

Placebo-Controlled Studies

304

320

Flexible Dose

Placebo

Placebo

Pristiq 200-400 mg

Pristiq 200-400 mg

0 -3 -6 -9 -12 -15

*

*

**

Placebo

Placebo

Pristiq 400 mg

Pristiq 400 mg

Pristiq 200 mg

Pristiq 200 mg

Pristiq 100 mg

Fixed Dose

Study

306

308

0 -3 -6 -9 -12 -15






Effexor XR® Comparator

317

309

*

Placebo

Placebo

Pristiq 200-400 mg

Pristiq 200-400 mg

Effexor XR® 75-150 mg


304

320

Flexible Dose

Placebo

Placebo

Pristiq 200-400 mg

Pristiq 200-400 mg

0 -3 -6 -9 -12 -15

**

**

Placebo

Placebo

Pristiq 400 mg

Pristiq 400 mg

Pristiq 200 mg

Pristiq 200 mg

Pristiq 100 mg

Fixed Dose

Study

306

308




Primary Efficacy Variable (HAM-D17) Mixed Effects Model – Week 8

* p-value vs placebo ≤ 0.05


304

320

Flexible Dose

Fixed Dose

Effexor XR® Comparator

317

309

0 -3 -6 -9 -12 -15

Study

*

*

**

*

Placebo

Placebo

Placebo

Placebo

Placebo

Placebo

Pristiq 400 mg

Pristiq 400 mg

Pristiq 200 mg

Pristiq 200 mg

Pristiq 200-400 mg

Pristiq 200-400 mg

Pristiq 200-400 mg

Pristiq 200-400 mg



Pristiq 100 mg

-20

*

*

*

306

308

Pristiq™ and Effexor XR®

Comparative Studies in MDD

Two Effexor XR trials of identical design

Low dose Effexor XR (Study 309)

Titration with Effexor XR (not Pristiq)

High dose Effexor XR (Study 317)

Titration with Effexor XR and Pristiq

Flexible dose Pristiq, 200/400mg, placebo

Study design: Comparisons vs placebo

Post-hoc analysis: Allows Pristiq/Effexor XR comparison

DVS 309-EU and 317-US: Pooled Analysis Ham-D17 Total Score (Mixed Effect Model, ITT)

Pristiq™/Effexor XR®

Comparable MDD EfficacyPooled Post-Hoc Analysis

-16

-14

-12

-10

-8

-6

-4

-2

0

1 2 3 4 5 6 7 8Week

Cha

nge

from

Bas

elin

eH

am-D

17 T

otal

* *

**

* *

*

****

Placebo

Effexor XR75-150 mg

Effexor XR150-225 mg

Pristiq 200-400 mg

* P < 0.05 vs placebo

Pristiq™ MDD: Relapse PreventionClinically Important Result

Primary Efficacy Analysis

0 50 100 150

0.0

0.2

0.4

0.6

0.8

1.0

Sust

ain

e d R

e mis

sion

Po s

s ib i

li ty

Pristiq 200 mgPristiq 400 mg

Days on Double-Blind

Placebo


Efficacy on Vasomotor Symptoms

The Majority of Women Will Suffer Hot Flushes

0

10

20

30

40

50

60

70

38 44 46 50 52 54 56 58 60 62 66 72Age in Years

Hot Flush

% o

f W

omen

Source: Rodstrom K. et al. Menopause 2002 9(3): 156-161

Pristiq™: Effective in Treating VMS Associated With Menopause

Efficacy demonstrated at 100 mg, 150 mg in2 placebo-controlled studies

Primary efficacy – number and severity of VMS

Secondary efficacy – responder analysis, onset of action, number of awakenings at night due to VMS

Pristiq™: Effective in ReducingNumber of Moderate and Severe VMS

100 mg dose: p-value versus placebo < 0.05 at all time points150 mg dose: p-value versus placebo < 0.05 at all time points

2

3

4

5

6

7

8

9

10

11

12

13

0 1 2 3 4 5 6 7 8 9 10 11 12

Weeks

# o

f Fl

ushe

s

2

3

4

5

6

7

8

9

10

11

12

13

0 1 2 3 4 5 6 7 8 9 10 11 12

Weeks

# o

f Fl

ushe

s

Study 315 Study 319

Pristiq100 mg

Pristiq150 mg

Placebo

Pristiq 150 mg

Pristiq 100 mg

Placebo

Pristiq™: Reduction in Average Daily Number and Severity Score of Hot Flushes

Study 319, 100 mgn=162

Study 315, 100 mgn=145

0.0040.0010.0110.008Week 9

0.001<0.0010.0180.013Week 10

0.0020.0020.0040.013Week 11

p-Value vs PlaceboSeverity

p-Value vs PlaceboNumber

p-Value vs PlaceboSeverity

p-Value vs PlaceboNumber

Time Point

<0.001<0.001<0.001<0.001Week 1

0.004<0.0010.0190.020Week 5

<0.001<0.0010.0540.013Week 4

<0.001<0.0010.003<0.001Week 3

<0.001<0.0010.001<0.001Week 2

0.003<0.0010.0420.019Week 7

0.0050.0010.0290.018Week 8

0.0020.0020.0020.005Week 12

0.002<0.0010.0480.026Week 6

ITT LOCF

High Responder Rate in VMS

* p-value versus placebo <0.05

0%

20%

40%

60%

% S

ubje

cts

Wit

h >

75

%R

educ

tion

in H

ot F

lush

es *

* **

Placebo Pristiq™100 mg

Pristiq150 mg

Placebo Pristiq100 mg

Pristiq150 mg

Study 315 Study 319

Rapid Onset of Action

* p-value versus placebo <0.001

0

5

10

15

20

25

30

Tim

e in

Day

s

* * * *


Pristiq150 mg


Pristiq150 mg

Study 315 Study 319

Time (Days) to Reach a 50% Reduction in Number of VMS

Reduces Nighttime Awakenings Due to VMS

* p-value versus placebo <0.05; ** p-value versus placebo <0.001

-3.00

-2.00

-1.00

0.00

Red

ucti

on in

Num

ber

of N

ight

tim

e A

wak

enin

gs

* *

* **


Pristiq150 mg


Pristiq150 mg

Study 315 Study 319

-25

-20

-15

-10

-5

0

Total MoodScore Anger Hostility

TensionAnxiety Depression Fatigue

Placebo Pristiq 100 mg Pristiq 150 mg

Improves Mood in Non-Depressed Postmenopausal Women

Week 12 Data

* p-value versus placebo <0.05; Data on File (Pooled data from Studies 315 and 319)

PO

MS,

Ch

ange

Fro

m B

asel

ine

* *

*** * * *

™


Safety/Tolerability Profile

Safety and Tolerability Profile of Pristiq™(Adverse Reactions ≥ 5%)

Nervousness

Somnolence

Tremor

Sweating

Abnormal Vision

Mydriasis

Abnormal Ejaculation/Orgasm

Impotence (Male)

Asthenia

Hypertension

Anorexia

Constipation

Dry Mouth

Nausea

Vomiting

Dizziness

Insomnia

Most common adverse drug reactions (>5%), pooled data VMS+MDD

Consistent With the SNRI Class

Pristiq™/Effexor XR® Comparator StudiesCombined Data, Adverse Events >5%

Adverse Event (%)

Placebo (n=245)

Pristiq 200-400mg

(n=231)

Effexor XR 75-150mg (n=127)

Effexor XR 150-225mg

(n=117)

Asthenia 4% 9% 8% 6%

Hypertension 3% 5% 3% 6%

Tachycardia <1% 6% 0% 4%

Insomnia 9% 13% 11% 13%

Anorexia 1% 10% 5% 15%

Somnolence 7% 13% 9% 19%

Dry Mouth 4% 20% 13% 26%

Nausea 12% 38% 21% 29%

Vomiting 1% 7% 2% 3%

Sweating 4% 19% 9% 18%

Impotence <1% 9% 6% 11%

† Men only

†

MDD Program: Most Nausea Occurred During Week One

Wyeth data on file (MDD001 DAR)

0%

10%

20%

30%

40%

50%

1 2 3 4 6 8 8

Week of Treatment

Inci

denc

e of

Nau

sea Placebo (n=323)

Pristiq™ 100 mg (n=118)Pristiq 200 mg (n=307)Pristiq 400 mg (n=317)

MDD Pooled Fixed Dose Studies

MDD Program: Incidence of Discontinuation for Nausea By Week

Subjects in DVS SR Flexible Dose studies (309 and 317 @ 200-400 mg/day) are not included in this display

0

10

20

30

40

50

Week 1 Week 2 Week 3 Week 4

% S

ubje

cts

Placebo

Pristiq 100 mg

Pristiq 200 mg

Pristiq 400 mg

™

VMS Program: Most Nausea Occurred During Week One and Was Dose Dependent

Wyeth data on file

0%

10%

20%

30%

40%

50%

1 2 3 4 5-8 >12

Weeks of Treatment

Inci

den

ce o

f N

ause

a Placebo (n=323)Pristiq 50mg (n=149)Pristiq 100mg (n=495)Pristiq 150mg (n=336)Pristiq 200mg (n=409)

VMS Pooled Studies

™

12

Pristiq™ – Additional Features

No prolongation of QT interval

From thorough QTc study

Blood pressure, pulse rate increases consistent with SNRIs

100 mg/day: No consistent increase/decrease

Pristiq very low drug-drug interactions

Pristiq™ Phase 3 Summary

Efficacy MDD improved Ham-D17 – 100, 200 and 400 mgVMS reduced number/severity hot flushes – 100, 150 mg

Sleep, mood, awakenings due to hot flushes reduced Total mood score improved Satisfaction score positive – 100, 150 mg

Safety Early discontinuation rate below 10% at end of week 1 Tolerability profile improved after week 1

Predominant symptoms – nausea, dizziness, insomnia, somnolenceMedian duration of nausea: 3-4 days

Pristiq™ Low-Dose Program

MDD3 ongoing low-dose studies

50, 100 mg, placebo (2 studies U.S., EU)50, 100 mg, placebo, duloxetine

1 low-dose study to support registration in AsiaLow-dose drug-drug interaction studies underway

VMSTitration study – 25, 50, 100 mg (ongoing)

Conclusion

Pristiq™ provides a unique therapy for women transitioning through menopause and beyond

MDD

Effective antidepressant in men/women

May provide better efficacy in womenthan SSRIs

VMS – non-hormonal vasomotor symptom relief associated with menopause

Fibromyalgia – clinical program ongoing


Pristiq™ Will Broadenthe Reach of Our SNRI Franchise

Green = Effexor XR®

MajorDepressive

Disorder

MajorDepressive

Disorder

PanicDisorder

PanicDisorder

SocialAnxietyDisorder


GeneralizedAnxietyDisorder


Pristiq™ Will Broadenthe Reach of Our SNRI Franchise

Green = Effexor XR®

Blue = Pristiq™

Red = Effexor/PristiqPanic

DisorderPanic

Disorder





VasomotorSymptoms ofMenopause

VasomotorSymptoms ofMenopause

FibromyalgiaSyndrome

FibromyalgiaSyndrome

MajorDepressive

Disorder

MajorDepressive

Disorder

MDD NDA Dec 2005

VMS NDA June 2006Status


Pristiq™ Product Profilefor Major Depression or VMS

Can become the first and only SNRI proven to effectively address the distinctive symptoms and therapeutic needs of women with depressionassociated with menopause or vasomotor symptoms

Viviant™/Aprela™(Bazedoxifene)

and (Bazedoxifene/Conjugated Estrogens)

Alliance with Ligand Pharmaceuticals

Effective osteoporosis agent

Less potential to exacerbate hot flushes

Safe for breast and uterus

Minimal metabolic disturbances

Initial Target ProfileViviant™ (Bazedoxifene)

Effective osteoporosis agent

Less potential to exacerbate hot flushes

Safe for breast and uterus

Minimal metabolic disturbances

Evolving Target ProfileViviant™ (Bazedoxifene)

Source: National Osteoporosis Foundation

The Number of Women at Riskfor Osteoporosis Is Projected to Increase

From 30 to 41 Million by 2020

8 11

22

30

0

5

10

15

20

25

30

35

40

45

2002 2020

# o

f W

omen

in M

illio

ns

Osteoporosis Osteopenia

30 Million

41 Million

IncreaseIncrease

Source: Patient estimates derived using IMS National Prescription Audit data

The Majority of Women Who StoppedTaking ET/HT Did Not Switch to

Prescription Osteoporosis Brands

11.6

5.8

4.4

5.4

0

2

4

6

8

10

12

14

16

18

Pre-WHI Post-WHI

Est.

Pat

ient

s in

Mill

ions

Osteo BrandsOral ET/HT

16.0 Million

11.2 Million

Jan-Jun 2002 Jan-Jun 2004

- 5.8M

+ 1.0M

Viviant™(Bazedoxifene)

With FDA-approval, the first new SERMin nearly 10 years providing physicians a

new option for patients at risk of osteoporosis and fracture

With FDA-approval, the first new SERMin nearly 10 years providing physicians a

new option for patients at risk of osteoporosis and fracture

Prevent osteoporosis

Relief of vasomotor symptoms

Improved vulvovaginal atrophy

Neutral on breast

Amenorrhea

Endometrial protection without progestin

Improved quality of life

Patient Benefits

Vasomotor

Breast

Bone

Endometrium

Select Estrogen “Targets”

New Paradigmfor Menopause

Vagina

Aprela™(Bazedoxifene/Conjugated Estrogens)

The First TSEC or Tissue Selective Estrogen Complex


Wyeth’s analysis suggest that Viviant’sunique characteristics make it the onlySERM that could be combined into such

an estrogen complex

Wyeth’s analysis suggest that Viviant’sunique characteristics make it the onlySERM that could be combined into such

an estrogen complex


Aprela™: The Most Comprehensive Medicine for Menopause

TSEC

BreastBreast

EndometriumEndometriumBoneBone

VaginaVagina

VasomotorVasomotor

Aprela™ and Viviant™(Bazedoxifene/Conjugated Estrogens)

and (Bazedoxifene)




Flushing

Night sweats

Waking at night

Tiredness

Depressed mood

Irritability

Lack of self-confidence

Insomnia

Painful intercourse

Vaginal dryness

Occurs in ~50% of Women

Climacteric Complaints Related tothe Menopause

Menopause Specific Quality-of-Life (MenQOL)

Adapted from Blumel JE, et al. Maturitas 34:17-23, 2000

<0.0001p-Value

1.53Premenopause

Postmenopause 3.20

Vasomotor Vasomotor Domain ScoreDomain Score

Menopausal StageMenopausal Stage

0%

10%

20%

30%

40%

50%

60%

70%

38 44 46 50 52 54 56 58 60 62 66 72Age in Years

Hot Flush

% o

f W

omen

Source: Rodstrom K et al. Menopause 9(3): 156-161, 2002

The Majority of WomenWill Suffer Hot Flushes

Osteoporosis

Osteoporotic fracture:

Profound effect on health

↑ Mortality following hip fracture

↑ Disability

↓ Quality-of-Life (QOL)

Huge economic impact

U.S. costs ~ $17.9 billion/year

Increase in hip fractures after discontinuing HT following WHI†

† Abstract: RM Dell, MD et al; Presented: AAOS Annual Mtg March 22-26, 2006

Osteoporosis

Baseline 1 Year

Architectural Change One Year Postmenopause

Borah, et al; Dufresne, et al; Abstracts presented: OI World Congress on Osteoporosis, 2002.


Tissue Selective Estrogen Complex (TSEC)A New Paradigm for Menopausal Therapy

Clinical Rationale for a Tissue Selective Estrogen Complex (TSEC)

Current HT and SERMs have clinical drawbacks

TSEC may provide improved clinical benefits with fewer potential side effects

Program initiated in 1999

Maintain Leadership in Menopausal Health

Women’s Health Initiative Estrogen Alone Arm

Time, years

0.04

0.03

0.02

0.01

0.00

0 1 2 3 4 5 6 7 8 9

HR, 0.82(95% CI, 0.65-1.04)Log-Rank p =.10

CEE Alone

Placebo

Cu

mu

lati

ve H

azar

d

Adapted from Stefanick, M. L. et al. JAMA 2006;295:1647-1657.

Cumulative Hazard for Total Breast Cancers

Target

The Most Comprehensive Medicinefor Menopause

The Most Comprehensive Medicinefor Menopause

Optimal Targeted Response ofTissue Selective Estrogens Complex (TSEC)

TSEC

Increased Bone Mass

Vaginal Health

Improved Hot Flush

Prevent Endometrial Hyperplasia

Decreased Breast Tenderness

Tissue Selective Estrogen Continuum Defines Activity

17β-EstradiolBazedoxifene

Raloxifene

Anti-Estrogens

Estrogen Receptor

FullAntagonist

FullAgonist

TSECAprela™

17β-Estradiol

Raloxifene Lasofoxifene

TamoxifenViviant™

Antagonist AgonistEndometrialStimulation

M.B. Taylor, North American Menopause Society, October 2004

Viviant’s Endometrial Profile Permits TSEC Benefits

Viviant’s Endometrial Profile Permits TSEC Benefits

Tissue Selective Estrogen Continuum Defines Activity

Pilot Study on the Endometrial Effects of CombinedRaloxifene and Oral 17-beta Estradiol in PostmenopausalWomenM.B. Taylor, MD1, Y. Qu, Ph.D.1, S. Siddhanti, PhD1, L. Plouffe Jr, MD1.Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN.

Results….. By 52 weeks, ET (endometrial thickness) was significantly increased in the RLX+E group compared with baseline and the RLX group (p<0.05). Two women (4%) in RLX+E group and none in the RLX group had endometrial hyperplasia in the exit endometrial biopsy.

Abstract Presented: NAMS 15th Annual Meeting, Washington, DC; October 2004

Raloxifene and 17ß-EstradiolNAMS Abstract

Aprela™(Bazedoxifene/CE)

A New Paradigm

Relieve vasomotor symptoms


Improve vulvovaginal atrophy (VVA)

Excellent amenorrhea

No increased breast tenderness vs placebo

Provide endometrial protection

Improve quality-of-life

-10

-8

-6

-4

-2

0

0 1 2 3 4 5 6 7 8 9 10 11 12

Week

Adj

uste

d M

ean

Cha

nge

From

Bas

elin

e

Number of Moderate-to-Severe Symptoms

Aprela™ Effectively Treats Vasomotor Symptoms

Statistically significant at all end points vs placebo and 8 – 12 weeks vs raloxifeneData on file: Ph 3 BZA/CE analysis 3115A1-303 study

Phase 3 Study

Placebo

Aprela 20/0.625

Aprela 20/0.45

Raloxifene

p vs PBO ≤ 0.001 (all BZA/CE groups at 6, 12, 18 and 24m)* p vs RAL < 0.05

Aprela™ Prevents OsteoporosisLumbar Spine BMD

BMD change relative to placebo:20/0.625: ↑ 3.72% at 2y20/0.45: ↑ 3.61% at 2y

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

Adj

uste

d M

ean

% C

hang

e

*

*

**

**

**

Baseline Month 6 Month 12 Month 18 Month 24

Placebo

Aprela 20/0.625

Aprela 20/0.45

Raloxifene

p vs baseline ≤ 0.001 (all treatment groups at 6, 12, 18 and 24m)p vs PBO ≤ 0.001 (all BZA/CE groups at 6, 12, 18 and 24m)

* p vs RAL < 0.05

Aprela™ Prevents Osteoporosis at the HipHip BMD

Adj

uste

d M

ean

% C

hang

e


-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

*

BMD change relative to placebo:20/0.625: ↑ 2.10% at 2y20/0.45: ↑ 1.71% at 2y

Placebo

Aprela 20/0.625Aprela 20/0.45

Raloxifene

Aprela™ Provided Excellent Endometrial and Breast Safety/Tolerability

Phase 3

After 2 years of treatment with AprelaEndometrium

No difference from placebo4Endometrial hyperplasia4Endometrial thickness4Endometrial polyps

BreastNo difference in breast tenderness vs placeboNo difference in breast tenderness vs raloxifeneNo increased breast cancers

AmenorrheaNo Breakthrough Bleeding

Data on file: Ph 3 BZA/CE analysis 3115A1-303 study

Aprela™ 20/0.625Aprela 20/0.45

Placebo

0%

20%

40%

60%

80%

100%

1 2 3 4 5 6 7 8 9 10 11 12 13

Months

% Subjects With Amenorrhea Over 1 Year

AmenorrheaNo Breakthrough Bleeding

Aprela™ 20/0.625Aprela 20/0.45

Placebo

CE/MPA 0.45/1.5CE/MPA 0.625/2.5

0%

20%

40%

60%

80%

100%

1 2 3 4 5 6 7 8 9 10 11 12 13

Comparison to Prempro™ by Historical Data

Months

% Subjects With Amenorrhea Over 1 Year

Data on file: Ph 3 BZA/CE analysis 3115A1-303 study

ConclusionsAprela™ - The First TSEC

A New Class for Menopausal TreatmentProduct Profile

Relieves vasomotor symptomsPrevents osteoporosisImproves vulvovaginal atrophy (VVA)Excellent amenorrheaLess breast tendernessProvides endometrial protection without progestin

NDA filing: Late 2007

Most Significant Medical Advancein Menopausal Therapy

Most Significant Medical Advancein Menopausal Therapy

Viviant™ (Bazedoxifene)

Prevention & Treatment of Osteoporosis

Endometrial Disorder – Treatment Emergent Adverse Event (TEAE)

0

1

2

3

4

5

Placebo Viviant 10 Viviant 20 Viviant 40 Raloxifene 60

* Statistically significant to RLX and PCB

**

% P

atie

nts

With

End

omet

rial T

EAE

Includes Clinically Significant Endometrial Thickness, Hyperplasia, Polyp, and Carcinoma

™

-2.00

-1.00

0.00

1.00


Adj

uste

d P

erce

nt C

hang

eViviant™ Prevents Osteoporosis

Lumbar Spine BMD

p <0.001 vs. placebo for all BZA groups at each time pointNo statistically significant differences among BZA 10, 20, 40 mg at any time point

Viviant 10 mg

Viviant 20 mg

Viviant 40 mgRaloxifene 60 mg

Placebo

Conclusions Viviant™

Achieved osteoporosis prevention as measuredby BMD Good endometrial safety profile

Similar to placeboSide effect profile: Increase from placebo

Hot flush Venous thrombosis Leg cramps

Less breast tenderness versus placeboEffective new SERM

ConclusionsAprela™ and Viviant™

Aprela(Bazedoxifene/CE )

Viviant(Bazedoxifene)

Vasomotor Symptoms

Vulvovaginal Atrophy

Osteoporosis Prevention

Osteoporosis Prevention

Osteoporosis Treatment

TSEC SERM

Comprehensive Menopausal Therapy




The Most ComprehensiveMedicine for Menopause

The Most ComprehensiveMedicine for Menopause


Vasomotor relief

Relief of vulvovaginal symptoms


Achieving amenorrhea

Endometrial protection without progestin

Free of restriction on duration of use

Aprela™ Proposed Profile The Most Comprehensive Medicine for Menopause

The Next Generation ofMenopausal Therapy

Viviant NDA June 2006Aprela NDA Late 2007

Status


Aprela™, the most comprehensive medicine for menopause, that provides both symptom relief and prevention of osteoporosis without progestin

Viviant™ provides physicians a new option for postmenopausal osteoporosis

Lybrel™(90 µg Levonorgestrel/20 µg Ethinyl Estradiol)

Lybrel™ Provides Women With the Potential to Reduce or Eliminate the Bleeding and Other Cycle Related Symptoms Associated With Their Period

Low-dose oral contraceptive

Designed to be taken 365 days a year without a placebo

Lybrel™(90 µg Levonorgestrel/20 µg Ethinyl Estradiol)




16 Million Women Indicate They Want Control of Their Periods

Findings from extensive market research:

Globally 47% of women say their period is extremely inconvenient

Over 30% of women never want theirperiod again

Reference: Gallup Study, 2004

Significant Segment of Women >18 Years Are Interested in Menses Inhibition

64%60%

64%64%60%

65%70%

74%

0%

10%

20%

30%

40%

50%

60%

70%

80%

Total 18-24 25-39 40-49

Age

Per

cen

t o

f W

om

en

Interest in not having periodInterest in contraceptive that reduces number of periods

Reference: Consumer Attitudes & Usage Study, 2005

Women Report Experiencing a Range of Symptoms With Their Cycle

Physical Symptoms

82%73%

60% 62%56%

41%

26%

Cram

ps

Bloa

ting

Brea

st T

ende

rnes

sFo

od C

rave

Head

ache

Wei

ght G

ain

Diffi

culty

Sle

epin

g

Gallup, 2004; PMS Oral Contraceptive Study, October 2004; Eidetics, November 2004

Emotional Symptoms

68%56% 54%

36% 31% 30% 28%

Moo

d Sw

ing

Fatig

ue

Irrita

bilit

yDe

pres

sion

Diffi

culty

Con

cent

ratin

gLo

w Se

x Driv

e

Anxi

ety

Women Manage Around Their Period

Often take multiple medications to address symptoms:HeadacheCrampsBloatingMood Changes/PMS

Often feel less effective at work and schoolAdjust their daily life

Avoid sexual activityWear dark, loose fitting clothesLimit exercise, activitiesStay home more, absenteeismSleep a lot

Reference: Eidetics, Positioning & Segmentation; 2004

Overview of Menstrual Cycle

0 7 14 21 24 287 14 21 24 287 14 21 24

Estrogen

Progestin

0 0

Men

ses

28

Men

ses

Day

NormalCycle

Men

ses

Traditional Contraception

0 7 14 21 24 287 14 21 24 287 14 21 24

Estrogen

Progestin

0 0

Men

ses

28

Men

ses

Day

NormalCycle

Men

ses

0 287 14 21 24Day

287 14 21 24

Hormone Placebo

287 14 21 24

Men

ses

Men

ses

Estrogen

Men

ses

Typical 21-Day Combined Oral Contraceptive

Continuous Contraception Opportunity

0 7 14 21 24 287 14 21 24 287 14 21 24

Estrogen

Progestin

0 0

Men

ses

28

Men

ses

Day

Men

ses

0 287 14 21 24 287 14 21 24

Day287 14 21 24

Estrogen

Progestin

Lybrel™ Regimen

0 287 14 21 24Day

287 14 21 24

Hormone Placebo

287 14 21 24

Men

ses

Men

ses

Estrogen

Men

ses

NormalCycle

Typical 21-Day Combined Oral Contraceptive

The Rationale Behind Lybrel™Indication: Submitted for contraception, menses inhibition and cycle related symptoms (CRS)

Rationale for component drugs

LNG is one of the best-studied progestins and a standard for OC safety

EE is the standard estrogen for OCs

Rationale for doses – Lybrel: Lowest daily dose

LNG 90 μg: Minimum effective dose for complete (100%) ovulation inhibition

EE 20 μg: Lowest EE dose with proven safety profile

LNG and EE – Lower daily and cumulative yearly dose, than higher-dose, 21-day cyclic OCs

Lybrel™Combined Phase 3 Pearl Index

† Pearl Index was based upon 18,533 28-day intervals and 13 pill packs per year

1.05 Method Failures

1.33†All Subjects

0.28User Failures

Combined Results of 2 Pivotal Trials

Bleeding Definitions

28-day pill pack bleeding classifications

Wyeth definitions based on days of bleeding and/or spotting

Amenorrhea: No bleeding or spotting days

No bleeding: No bleeding days (with or without spotting days)

Data on file, Wyeth Pharmaceuticals Inc.

Lybrel™Provided Reversible Menses Inhibition

0

20

40

60

80

100

1 2 3 4 5 6 7 8 9 10 11 12 13

Amenorrhea No Bleeding

Pill Pack

% o

f Su

bjec

ts No sanitary

protection needed

Percent of Women With Amenorrhea or No Bleeding

Cycle Related Symptoms (CRS)

0

2

4

6

8

10

12

14

16

18

Baseline 1 2 3

Mea

n P

rem

enst

rual

P

enn

DSR

Su

bsca

le S

core

**

*

Pill Pack

MoodBehavioralPainPhysical

* p <0.001 vs baseline

Lybrel™ Was Effective for All Domains

Lybrel™Improves Dysmenorrhea

0

2

4

6

8

10

Baseline Pill Pack 1 Pill Pack 2 Pill Pack 3

Cramps

* All scores decreased from baseline (p<0.001); except for total score at pill pack 1

Me a

n S

c ore

**

**

**

0

10

20

30

40

50

60

Baseline 1 2 3

Lybrel™Improves Work Productivity

Historical comparison baseline scores: Major depressive disorder = 39.4; Normative population = 22.3.

Pill Pack

PMS Dysmenorrhea

* **

* p <0.001, decrease from baseline

T ot a

l Mea

n E

WP

S S c

ore

Imp r

o ve m

ent

** *

Return to Menses After > 6 Months on Therapy

Median time to return to menses was 32 days

97% of women had return to menses in ≤90 days

No difference on return to menses, no matter how long on therapy

1–30 days 31–60 days61–90 days>90 days Pregnancy before menses onset

Lybrel™ Summary

LNG/EE continuous-use regimen is effectiveand safe:

Lowest daily dose

Combined Pearl Index comparable to recently approved OCs

Safety profile similar to low-dose 21-day cyclic regimen OCs

Lybrel™ Summary(Cont’d)

LNG/EE continuous-use has unique clinical benefits:

Cycle relief

Menses inhibition – induction of amenorrhea and rapid onset of no bleeding

Rapid reduction of cycle related symptoms (CRS) including PMS, dysmenorrhea and cyclic symptoms

Improvement in work productivity in those significantly impaired at baseline

PMS/PMDD evaluations – ongoing

Lybrel™ Conclusion

Lybrel is a novel, continuous use oral contraceptive that provides:

Contraceptive efficacy

Inhibition of menses

Control of cycle related symptoms (CRS)

Growth Driven by Claimed Benefits Beyond Contraception

Ortho EvraNuvaring Convenience

Seasonale 4 Annual Periods

Ortho Tri-Cyclen Lo Lower Hormones

Yasmin Weight Loss

Loestrin 24 FeYaz Shorter Periods

Product Benefit

Significant Segment of Women > 18 Years of Age Are Interested in Menses Inhibition

64%60%

64%64%60%

65%70%

74%

0%

10%

20%

30%

40%

50%

60%

70%

80%

Total 18-24 25-39 40-49

Age

Per

cen

t o

f W

om

en

Interest in not having periodInterest in contraceptive that reduces number of periods

Source: Consumer Attitudes & Usage Study, 2005

Lybrel™

Lybrel is a new low-dose oral contraceptive of choice for women who prefer ongoing relief from bleeding and the other cycle related symptoms experienced with their period

NDA May 2005Status

> $250 MillionPeak Sales

Torisel™(Temsirolimus)

Torisel improves overall survival in patients with advanced renal cell cancer

Torisel as a single agent is well tolerated in patients with advanced renal cell cancer

Torisel preserves patient’s quality-of-life

Potential to help acute patients live longer and feel better

Torisel™ Is a Unique and Effective New Treatment for Cancer Therapy

Help Renal Cell Cancer PatientsLive Longer and Feel Better

Help Renal Cell Cancer PatientsLive Longer and Feel Better



Joseph Camardo, M.D.Senior Vice President

Global Medical Affairs and North American Medical Director, Wyeth Pharmaceuticals

Renal Cell Cancer Is a Serious Disease With Limited Treatment Alternatives

Renal cell cancer (RCC) often asymptomatic and diagnosed when it has already spread

Survival after diagnosis of metastatic cancer often shorter than one year

Current drugs show

Modest efficacy

Significant morbidity

No improvement in survival

Torisel™ Binds mTOR andBlocks Cancer Cell Proliferation Pathways

Renal Cancer Cell

Growth Factor

mTOR Target of Rapamycin

RNA Transcription

Protein Production

PI3_K Signal Pathway

Surface Receptor

Blood Vessel Growth Cell Division

Torisel

RNA Transcription

Protein Production

Cell DivisionBlood Vessel Growth

Growth Factor

Interferon: escalating to18 MU SC TIWInterferon: escalating to18 MU SC TIW

n = 207

Torisel™: 15 mg IV q wk+ Interferon: 6 MU TIWTorisel™: 15 mg IV q wk+ Interferon: 6 MU TIW

626 patients with advanced RCC and no prior treatment

209 sites

26 countries

RANDOMIZE

RRAANNDDOOMMIIZZEE

Torisel™: 25 mg IV q wkTorisel™: 25 mg IV q wkn = 209

n = 210

A RC C

Patients

IntermediateSurvival

LongerSurvival

Very ShortSurvival

RCC patient population represents a spectrumof severity

The ARCC Patients in General Had Advanced Disease and Limited Survival

Torisel™ targets

Patients with thegreatest need

Patients with resistant disease

0.0078

49%

10.9 mo

143209

ToriselTorisel

210207Patients

0.6965Log Rank p-Value Stratified

8.4 mo7.3 moMedian Overall Survival

15%

152

InterferonInterferon+ Torisel+ Torisel

149

InterferonInterferon

% Improvement in Survival

# Deaths

Based on Data for Wyeth NDA

Torisel™ Is the First New Drug Shown to Significantly Improve Survival in RCC

Overall Survival Extended by More Than 3 Months With Torisel™

0.00

0.25

0.50

0.75

1.00

0 5 10 15 20 25 30

Time to Death (Months)

Surv

ival

Dis

trib

utio

n Fu

ncti

on

Torisel

IFN

10.9 mo7.3 mo

FromARCC Study

0.0001

77%

5.5 mo

192209

ToriselTorisel

210207Patients

0.0040Log Rank p-Value Stratified

4.9 mo3.1 moMedian PFS

58%

168

Interferon + Interferon + ToriselTorisel

153

InterferonInterferon

% Improvementin PFS

# Patients with Assessment

Progression-Free Survival (PFS) Extended in Torisel™ Treated Patients

Based on Data for Wyeth NDA

Progression-Free Survival Improved By More Than 2 Months With Torisel™

0.00

0.25

0.50

0.75

1.00

0 5 10 15 20 25 30Months from First Dose

Pro

babi

lity

of P

rogr

essi

on-F

ree

Surv

ival Torisel

IFN

FromARCC Study

Torisel™ Is Safe and Well Tolerated in Patients With Renal Cell Cancer

Common side effects: mucositis, anemia, hyperlipidemia, rash, infection

Treatable and most often did not requiredose modification

Fewer patients were discontinued due toside effects relative to interferon (18% vs 30%)

Fewer patients had serious side effects relative to interferon (38% vs 48%)

Fewer patients required dose reduction relative to interferon (20% vs 38%)

TWiST measures: Time Without Symptoms of progression or Toxicity

The measurement for TWiST is time in months

Q-TWiST incorporates the patient’s assessment of the quality of survival

The measurement for Q-TWiST is quality-adjusted months

Health State Analysis Is an Important Measure of Cancer Therapy Effectiveness

Revicki, DA, Feeny, D, Hunt, TL, et al. Analyzing Oncology Clinical Trial Data Using the Q-Twist Method: Clinical Importanceand Sources for Health State Preference Data. Quality of Life Research, 2006;15:411-423.

Patients on Torisel™ Live Longer and Maintain Quality of Life

0

2

4

6

8

10

TWiST

Mon

ths

Interferon

Torisel

* Torisel significantly better, p=.0005

*

Q-TWiST

Interferon

Torisel*

Torisel extends time without symptoms of progression or toxicity

InterferonPlaceboInterferonComparator

1st Line Good/ Intermediate Prognosis

n=750

Sutent

2nd Line Good/ Intermediate Prognosis

n = 769 patients

Nexavar(current indication)

1st Line Poor/ Intermediate Prognosis

n = 626 patients

Study Population

Torisel

Torisel™ Is Unique Among the New Drugs

120% improvement

11 vs 5 months

99% improvement

5.9 vs 2.8 months

77% improvement

5.5 vs 3.1 months

Progression-free survival

Survival No significant improvement

No significant improvement

49% improvement10.9 vs 7.3 months

Torisel alone improves overall survival (49%) in patients with advanced renal cell cancer

Median increase in survival is 3.6 months The result is clinically significant and highly statistically significantEffective in patients with poor and intermediate prognosis

Torisel also preserves patients’ quality of life

Torisel™ Is a Unique and EffectiveNew Treatment for Renal Cell Cancer

Only Agent to Show an RCC Survival Benefit

Positions Torisel to be RCC Drug of ChoicePositions Torisel to be RCC Drug of Choice


Torisel is the 1st targeted therapy proven to extend survival and maintain quality-of-life in patients with advanced renal cell cancer

NDA Late 2006Status

$500 Million*Peak Sales

Torisel™ Product Profile

* Includes indications for RCC, MCL

Tygacil®(Tigecycline)

Source: IMS’ Quarterly Midas (Aug 06); Injectable Antibiotic Market excludes Japan, IMS’ data for Latin America does not include hospitals, thus understating performance in this region.*2006 estimated based on annualized 1H06

$0

$200

$400

$600

$800

$1,000

$1,200

2000 2002 2004 2006*

Sale

s $U

S D

olla

rs (0

00s)

Wyeth Is theGlobal Anti-Infectives Market Leader

Rocephin

Primaxin

Merrem

Cipro

Hospital-Wide Resistance

Tygacil®, A Potential Solution to the Global Concern of Antibiotic Resistance

United States

MRSA 34%VRE 17%ESBL (K. pneumoniae) 8%

Europe

MRSA 26%VRE 1%

23%ESBL (K. pneumoniae)

Asia Pacific

MRSA 46%VRE 1%


Latin America

MRSA 35%VRE 2%


Source: SENTRY Data 2001Definitions: (MRSA) methicillin-resistant staphylococcus aureus, (VRE) vancomycin-resistant enterococcus,(ESBL's) extended spectrum beta lactamases

Nausea/VomitingYesYesYesBIDTygacil

No

No

No

Yes

Free From Free From Drug Drug

MonitoringMonitoring

No

No

No

No

Low Drug Low Drug InteractionsInteractions

Hyper-sensitivityNoQD +

q6-8hRocephin + Vancomycin

GI / Hyper-sensitivityNoQ12 +

q6-8hPrimaxin + Vancomycin

GINoq6-8hTazocin + AG

CNS/GINoQD + q6-8h

Levaquin + Anaerobic*

TolerabilityTolerabilityFree From Free From

Renal Renal AdjustmentAdjustment

DosingDosingRegimensRegimens

* Metronidazole

Tygacil® Reduces the Complexity of Antibiotic Treatment

Excellent Performancein Our Global Launch Year

Approved in 38 countries

Launched in 16 countries

24 further approvals are expected byend of 2006

U.S. > $60 million in first full year on market

50,000 U.S. patients treated

U.S. hospital formulary acceptance > 90%

Source: SENTRY

Tygacil®(Tigecycline)



Tygacil® Target: For Serious Infections…the First Expanded Broad Spectrum Antibiotic

Patients with acute infections, who need to beadmitted to the hospital, are increasingly likely to have a resistant organism

Tygacil developed to combine:

Treatment for gram-positive resistant bacteria including resistant Staph. aureus

Treatment for gram-negative bacteria including resistant organisms

Treatment for atypicals and anaerobes

Greater likelihood of effective treatment thefirst time

Data on file, Wyeth Pharmaceuticals Inc.

Tygacil® Is Highly Effective for Complicated Skin and Abdominal Infections

Cu

re R

ate

(%)

Tygacil Vancomycin Plus Aztreonam

Imipenem-Cilastatin

87 8689 86

0

20

40

60

80

100

Complicated Skin and Skin Structure Infections

(cSSSI)

Complicated Intra-Abdominal Infections (cIAI)

30

Pneumonia Is a SeriousMedical Problem

Patients often require hospitalization

Mortality rate is 12%

Mortality is substantially higher in patients with heart disease or respiratory disease

Resistant organisms are becoming more prevalent

Resistance increases risk of mortality

The Wrong Empiric Selection HasDire Effect on the Patient

In hospital-acquired pneumonia1

All-cause mortality

12.2% vs 52.1%when the empiric choicedoes not cover thecausative bacteria

0

10

20

30

40

50

60

AdequateCoverage

InadequateCoverage

Mortality Rates

1 Kollef M, Chest, 19992 Houck PM, Arch IM, 2004

“ In community-acquired pneumonia, appropriate antibiotic therapy within four hours of ER arrival had lower mortality and shorter length of stay.”2

% M

orta

lity

Tygacil® Pneumonia and Resistant Pathogens Program

Community-Acquired Pneumonia (CAP)

2 studies completed (900 patients)

Hospital-Acquired Pneumonia (HAP)

1 study (860 patients) completed by year-end

Resistant Pathogens submission (RP)

3 organisms on the IDSA hit list

NDA Filing Mid-2007NDA Filing Mid-2007

* p < 0.001 for Non-Inferiority

Tygacil® Matches the Leading Quinolone for Community Acquired Pneumonia

0

20

40

60

80

100

Study 308 * Study 313 *

Cur

e R

ate

(%)

Tygacil Levofloxacin

82.4

94.9

100

94.7

95.7

Tygacil Tygacil % of Patients Cured% of Patients Cured

Clinical Cure RatesClinical Cure Rates

81.3H. influenzae

88.6S. pneumoniae (culture)

100Legionella pneumoniae

91.7Mycoplasma pneumoniae

96.3Chlamydia pneumoniae

LevofloxacinLevofloxacin% of Patients Cured% of Patients CuredIsolateIsolate

Tygacil® Demonstrates Broad Spectrum Efficacy in Pneumonia

Data from Phase 3 studies

Tygacil® Resistant Pathogens Program

Worldwide clinical trial

Patients with skin, abdominal, respiratory or systemic infections

Infectious organism determined to bemulti-drug resistant

Acinetobacter baumannii

Klebsiella pneumoniae

Tygacil® Resistant Pathogens ProgramClinical Cure Rates (Ongoing Study)

IsolateIsolate

11/11 (100%)14/17 (82%)TOTAL

1/1 (100%)3/4 (75%)HAP

6/6 (100%)-cIAI

4/4 (100%)11/13 (85%)cSSSI

K. pneumoniaeK. pneumoniaeA. baumanniiA. baumanniiDiagnosisDiagnosis

‡‡Quinolones

‡3rd/4th

Gen Cephs

Tazocin

Carbapenems†

Tygacil

PseudoPseudoAtypicalAtypical

Resistant Resistant Gram Gram

NegativeNegative


PositivePositiveAnaerobeAnaerobeGram Gram

NegativeNegativeGram Gram

PositivePositive

Source: Wyeth GMA Literature Review; Competitive Information Report† Excludes Ertapenem, which has no pseudomonas coverage‡ Varies by product within class

Expanded broad spectrumExpanded broad spectrum

Pneumonia and RP Studies Complete the Expanded Broad Spectrum of Tygacil®

‡‡Quinolones

‡3rd/4th

Gen Cephs

Tazocin

Carbapenems†

Tygacil

PseudoPseudoAtypicalAtypical


NegativeNegative


PositivePositiveAnaerobeAnaerobeGram Gram

NegativeNegativeGram Gram

PositivePositive

Expanded broad spectrumExpanded broad spectrum

Pneumonia and RP Studies Complete the Expanded Broad Spectrum of Tygacil®

Source: Wyeth GMA Literature Review; Competitive Information Report† Excludes Ertapenem, which has no pseudomonas coverage‡ Varies by product within class

Tygacil® Safety and Tolerability

Current label indicates caution for patients with clinically apparent bowel perforation

Based on data from Phase 3 studies

Most common adverse events

Nausea and vomiting

Generally transient, do not lead to discontinuation

Notable is the absence of:

Renal impairment

Liver impairment

Tygacil® Is a Strong New Entry in a Challenging Medical Area

Excellent new data in two areas

Pneumonia indication adds to the clinical value beyond abdominal and skin infections

Effectiveness against atypical and resistant pathogens confirms and expands the spectrumof activity

Tygacil meets the demand

For innovation in the field of Infectious Disease

For efficacy in patients with serious infections

First-in-class, expanded broad spectrumIV antibiotic

Tygacil® Product Profile

Foot2%

SBF14%

All Others19%

Bone/Joint2%

CAP23%

HAP14%

IAI15%

SSSI11%

Almost 40% of I.V. Antibiotic Patients Are Added With HAP/CAP Indications

US 2005 Patient Share by Disease Staten = 12.7 Million Patients

Source: Syndicated AMR Hospital Data 2005 Update, September 2006Definitions: (HAP) Hospital-Acquired Pneumonia, (CAP) Community-Acquired Pneumonia, (IAI) Intra-Abdominal Infection, (SSSI) Skin and Skin Structure Infection, (SBF) Septicemia/Bacteremia/Febrile Neutropenia

37%HAP / CAP

26%IAI / SSSI

First-in-class, expanded broad spectrumIV antibiotic

Tygacil® Product Profile

Launched for cIAI, cSSSI

NDA for CAP/HAP and Resistant Pathogens Mid 2007

Status


Current indications for cIAI and cSSSI

CAP/HAP/RP indications coming

Monotherapy, empiric treatment for serious, complicated or resistant infections

Bifeprunox

Alliance with Solvay in theUnited States, Canada and Mexico

Bifeprunox ExpectedAdvantages

No weight gain

Minimal glucose dysregulation

Favorable lipid profile

No increase in prolactin

Current TherapyLimitations

Excessive weight gain

Glucose abnormalities

Limitations of Antipsychotic Therapies

Triglyceride elevation

Hyperprolactinemia

Bifeprunox

With FDA-approval, long-term maintenance option when metabolic disturbances

associated with other antipsychotics are getting in the way of long-term treatment

With FDA-approval, long-term maintenance option when metabolic disturbances

associated with other antipsychotics are getting in the way of long-term treatment

Bifeprunox

R. Michael Poole, M.D., F.A.C.P.Vice President, Neuroscience

Therapeutic Area DirectorWyeth Research

Schizophrenia: The Most Serious Mental Illness Known

Generally a lifelong illness marked by acute and stable episodes

<25% are employable

50% of patients attempt suicide, 10% complete

20% shorter lifespan, much due to cardiovascular and metabolic diseases that are exacerbated by many current therapies

CATIECATIENIMH trial of outpatient schizophrenia treatment1460 patients treated for 18 months74% of patients discontinued treatment earlyKey insight: individualized treatment is critical

Hyper-prolactinemia

Hyper-prolactinemia

Long-Term Side Effects of Antipsychotic Drugs: Shift in Risk1

EPS + TDEPS + TD

Weight Gain

Weight Gain

InsulinResistance

InsulinResistance

Hyper-glycemiaHyper-

glycemia

CVD

Dys-lipidemia

Older“Typical” Agents

QTcQTc

Neurologic Side EffectsNeurologic Side Effects

1.Modified from :Scott Stroup, MD, MPH; University of North Carolina at Chapel Hillhttp://www.nasmhpd.org/general_files/meeting_presentations/Win05PowerpointsforWeb/ScottStroup.ppt

Long-Term Side Effects of Antipsychotic Drugs: Shift in Risk1

QTcQTc

Newer“Atypical” Agents

Weight Gain

Weight Gain

Diabetes

Hyper-GlycemiaHyper-

Glycemia

InsulinResistance

InsulinResistance

CVD

DyslipidemiaEPS +

TDEPS +

TD

EPS + TDEPS + TD

Weight Gain

Weight Gain

InsulinResistance

InsulinResistance

Hyper-glycemiaHyper-

glycemia

CVD

Dys-lipidemia

Older“Typical” Agents

QTcQTc

Neurologic Side EffectsNeurologic Side Effects

1.Modified from :Scott Stroup, MD, MPH; University of North Carolina at Chapel Hillhttp://www.nasmhpd.org/general_files/meeting_presentations/Win05PowerpointsforWeb/ScottStroup.ppt

Hyper-prolactinemia

Hyper-prolactinemia

Hyper-prolactinemia

Hyper-prolactinemia

Metabolic Syndrome and Cardiovascular Disease Are Significant Problems for Patients With Schizophrenia

1. McEvoy JP, Meyer JM, Goff DC, et al. Schizophr Res. 2005;80:19-32. 2. Ösby U, Correia N, Brandt L, et al. BMJ. 2000;321:483-484. 3. Harris EC, Barraclough B. Br J Psychiatry. 1998:173:11-53. 3. Hennekens C.,American Heart J 2005;150:11115-21.

Metabolic Syndrome in Schizophrenia

0%

25%

50%

75%

100%

Males Females

Per

cen

tage

of

Pat

ien

ts w

ith

Met

abol

ic S

yndr

ome

U.S. General PopulationSchizophrenia

*

*

*P=.001

0

1

2

3

4

5

1976-80 1981-85 1986-90 1991-95

Years

Sta

nda

rdiz

ed M

orta

lity

Rat

ios

Male

Female

Cardiovascular Mortality in Schizophrenia

Weight Gain Causes Problems in Other Areas

Significant weight gain and obesity have important negative effects on:1

Adherence to medication regimens

Adjustment in the community

Self-image

Ability to participate in rehabilitation

1 Marder SR, Essock SM, Miller AL, et al. Am J Psychiatry. 2004;161:1334-1349

“Jonathan”24-year-old with schizophrenia since the age of 17

Relatively stable (no hospitalization for past 3 years)Currently living in a personal care homeBags groceries 4 hours/day for 2 days a weekDay treatment program 3 days a week

Currently on olanzapine 20 mg and buproprion SR 200 mg daily Had breakthrough psychotic episodes on risperidoneand ziprasidone

Weight gain of 60 lbs since treatment initiated with olanzapine BMI of 33Unsuccessful trial of Xenical

Diagnosed with Type II diabetes and hypercholesterolemiaUnable to control dietNon-adherent to exercise program

BifeprunoxOverall Conclusions From Clinical Program

Bifeprunox is a valuable treatment for stable patients with schizophrenia

Effective at maintaining stability in chronic patients

Metabolic effects similar to placebo, superior to comparators

Bifeprunox is effective for acute exacerbations of schizophrenia

Bifeprunox is best suited for chronic stable patients with metabolic derangement from other medications

Short-Term Studies in Acute Exacerbation of Schizophrenia

Bifeprunox was effective in 2 of 3 short-termstudies in the relevant dose range when compared with placebo

20 mg in the 2010 study

30 mg in the 3001 study

Smaller mean effects seen on primary efficacy measures than with risperidone or olanzapine

Titration required to maximize tolerability

Favorable effects on weight gain, lipids, glucose andprolactin measures

Study 3001: EfficacyBifeprunox 30 mg Significantly Better Than Placebo

PANSS Total Score - Change from Baseline LOCF-ITT

* p < 0.05 bifeprunox versus placebo, based on LS means

Recommended Dose

-25

-20

-15

-10

-5

0

0 1 2 3 4 5 6

Mea

n C

han

ge F

rom

Bas

elin

e

** *

Bifeprunox 40 mg

Placebo

Bifeprunox 30 mg

Risperidone 6 mg

Study 3001: SafetyBifeprunox Patients Lost Weight on Average

Compared With Placebo and Risperidone

-3-2-10123456

Placebo Bifeprunox 30 mg Bifeprunox 40 mg Risperidone 6 mg

Weight Change at Endpoint (LOCF)

Wei

ght

Ch

ange

(Lb

s)

*

* *

Recommended Dose

* Significant versus placebo

6-Month Relapse Prevention Studyin Stable Chronic Schizophrenia

Bifeprunox effectively maintained schizophrenia stability compared with placebo

Bifeprunox showed favorable effects on:

Weight gain

Lipid profiles

Metabolic syndrome

Serum prolactin

Study 10214:6-Month Relapse Prevention Study Design

3-6 daysdrug freelead-in

Term.Month 6

20 mg/day bifeprunox

30 mg/day bifeprunox

Placebo

Double-Blind Treatment

RandomizeBaselineDay 1

ScreeningDay

-6 /-3

Recommended Dose

Study 10214 Efficacy:Bifeprunox Patients Remained Relapse-Free Longer Than Placebo Patients Over 6 Months

Recommended Dose

0.00.10.20.30.40.50.60.70.80.91.0

0 30 60 90 120 150 180Time in Days

Kap

lan-

Mei

er E

stim

ates

p-value = 0.008

Bifeprunox 20 mg

Bifeprunox 30 mg

Placebo

Study 10214 Efficacy:Schizophrenia Symptoms Were Stable

Over 6 Months on Bifeprunox Treatment

Mean PANSS Score

Recommended Dose

Mea

n C

han

ge F

rom

Bas

elin

e

Bifeprunox 30 mg - ∗p< 0.025, ∗∗p< 0.005 Bifeprunox 20 mg - ∗p< 0.025, ∗∗p< 0.005

0 30 60 90 120 150 180Days

∗ ∗∗ ∗∗ ∗∗ ∗∗ ∗∗ ∗∗∗∗ ∗∗∗∗∗∗∗∗

10

0

-10

Placebo

Bifeprunox 20 mg Bifeprunox 30 mg

Study 10214 Safety:Bifeprunox Patients Lost Weight on Average

After 6 Months

* p < 0.05 bifeprunox versus placebo

-5

-4

-3

-2

-1

0

Placebo Bifeprunox 20 mg Bifeprunox 30 mg

*

Wei

ght

Ch

ange

Fro

m B

asel

ine

(Lbs

) Mean Weight Change

Recommended Dose

Study 10214 Safety:Bifeprunox Had Favorable Effects on Lipids

Change in Fasting Lipid Values

Recommended Dose

-0.5

0

0.5

TotalCholesterol

LDL HDL Triglycerides

Mea

n %

Ch

ange

Fro

m B

asel

ine

PlaceboBifeprunox 20 mgBifeprunox 30 mg

Study 10214 Safety:Bifeprunox Did Not Cause Metabolic Syndrome

0%

10%

20%

30%

40%

50%

Placebo Bifeprunox 20 mg Bifeprunox 30 mg

Definition of assessable: 4 or more MS criteria have been measured MS present: 3 or more MS criteria are fulfilled

% Patients with Metabolic Syndrome

Recommended Dose

BaselineEnd ofStudy

Baseline End ofStudy

Baseline End ofStudy

BifeprunoxNear-Term Objectives

File NDA in 2006 for treatment of schizophrenia and maintenance of stability

Complete ongoing short-term comparative studies

Initiate long-term comparative studies

Initiate studies to explore ways to simplify dose titration

Finalize data on bipolar depression from the Phase 2 POC study

Bifeprunox Target Market U.S. Example

Source: IMS' National Sales Perspective, MAT 7/2006Acute sales = non federal hospitals, federal facilities, Maintenance = retail, LTC, mail, clinics, misc, home healthcare, HMO

U.S. Atypical Market – Maintenance Segment

~30% - 40% of MaintenancePatients Have

Metabolic Syndrome

$10 Billion Maintenance Market

* Sales for Wyeth / Solvay Alliance territories only; the United States, Canada and Mexico

Alliance with Solvay Pharmaceuticals

Bifeprunox Safely Maintains Stability in Schizophrenia

Relief for patients where metabolic changes have challenged their long-term therapy

Improved side effect profile

No weight gain

Favorable lipid profile

Minimal risk for glucose dysregulation

Lack of hyperprolactinemia

NDA 2006Status

$500 Million to $1 BillionPeak Sales

Methylnaltrexone

Alliance with Progenics

Significant Unmet Medical Need in Two Specific Areas

Opioid Induced Constipation (OIC)A common side effect that can be a barrier to effective pain managementLaxative therapies not always effectiveNo medicines approved to treat OIC

Post Operative Ileus (POI)A complication of surgery that delays recovery and can extend hospital stayNo medicines approved to treat POI

OIC is Drug-Induced Dysfunctionof the GI Tract

Many Causes of Moderate to Severe Pain Where Opioids Are Commonly Prescribed

Cancer

Osteoarthritis

Low Back Pain

Fibromyalgia

Post-Operative

Joint Pain

Post-herpetic Neuralgia

Diabetic Neuropathy

HIV

Juvenile Rheumatoid Arthritis

Spinal Stenosis

Burns

Herniated Discs

Trauma

Sickle Cell Anemia

Methylnaltrexone Is Not a Laxative

U.S. Commercial Performancefor Zofran®

Source: IMS NSP (Feb 2006) and IMS New Product Spectra (2006)1 Common Chemotherapy with Emetogenic Potential referred to as Platinum Coordination Chemotherapeutics per IMS class definition

$0

$1

$2

2005

Sal

es (

$ B

illio

ns)

Treatment of Side Effect, Compared to Large Treatment Class

$1.5 Billion

$1.2 Billion

Zofran Common Chemotherapywith Emetogenic Potential1

Annual Opioid Prescriptions(U.S. Data)

† IMS Health, NPA - Includes 2005 Rxs for morphine, hydrocodone, codeine, oxycodone, propoxyphene, meperidine,methadone and other synthetic narcotics.Longitudinal Patient Data -Opioid use days per annum: Short-Term = < 60 days, Long-Term = 61 –300 days, & Continuous = 300+days

0

50

100

150

200

TRx

(in

Mill

ions

)

60M60M

58M58M

97M

215 Million Annual Rxs†

Continuous UseContinuous Use

Long-Term UseLong-Term Use

Short-Term Use

~120 Million Continuous or

Long-Term Prescriptions

Large Market Opportunity –Opioid Induced Constipation (OIC)

(U.S. Data)

Estimated 5 Million Patients With OIC

4.6M4.6M

7.2M7.2M

Continuous UseContinuous Use

Long-Term UseLong-Term Use

~12M Patients Continuous or

Long-Term Use†

> 40 % Patients Experience

OIC

5.0 Million

Patients

5.0 Million

Patients

OICPopulation

(Est.)

† Longitudinal Patient Data – Opioid use days per annum: Short-Term = < 60 days, Long-Term = 61 –300 days, &Continuous = 300+days

All Neck/Back37%

Advanced Illness34%

Arthritis/Joint15%

All Other14%

OIC Population EstimateEstimated 5 Million Patients With OIC

~ 1.8 Million Patients in Initial Indication of Advanced Illness

(U.S. Data)

Source: Wyeth estimate based on IMS NDTI

Post Operative Ileus(POI)

Post Operative Ileus in the News

Pataki Recovering From New Surgery, February 22, 2006By Glenn Blain; Melissa Klein

Governor, In High Spirits, Joins Briefing On His IllnessMarch 2, 2006

By LAWRENCE K. ALTMAN and RICHARD PEREZ-PENA

Doctors at NewYork-Presbyterian/Columbia hospital said Mr. Pataki showed continued improvement, with signs that his abdominal infection and bowel paralysis were easing. But they said they did not know when he would be readyto be discharged.

22 Million Patients Undergo Surgical Procedures Requiring Pain Management (U.S.)

Post Operative Ileus (POI)Population Estimate

Source: Premier Database

2.4 MillionPatients

Low Risk Open

Surgery61%

Low Risk Laparo-scopic

Surgery28%

High Risk Open

Surgery11%

U.S. Economic Burden of Post Operative Ileus (POI)

Extended length of stay ranging between 2.35 and 3.00 days1*

Incremental charges ranged between $4,118 and $8,785 per hospitalization1*

* (p<0.001)1 Sarawate CA, Lin S-J, Walton SM, Crawford SY, Goldstein JL. Economic burden of post-operative ileus (POI) in

abdominal surgical procedures (abstract). Ann Pharmacother 2005;39:1502-10

Methylnaltrexone



HO O

N

OH

CH3

Morphine

Methylnaltrexone

HO O

N+

HO

O

CH3

Methylnaltrexone is a Mu opioid receptor antagonist

Does not cross theblood-brain barrier

Morphine acts centrally and peripherally

Opioids activate receptorsin the brain and providepain relief…

… but receptor activationin the GI tract results inconstipation.

Methylnaltrexone Is aSelective Opioid Antagonist

Reverses Opioid Induced Constipation without reversing analgesia or inducing withdrawal

Antagonizes peripheral, but not central opioidreceptors

Methylnaltrexone (SC) Phase 3 Trials Show Consistent Activity in Relieving Constipation

Two multicenter studies totaling 287 patients

Randomized, double-blind, placebo-controlled

Patients with advanced illness

Cancer, end stage pulmonary disease, HIV, others

Opioid Induced Constipation defined as:

On opioids for pain control

No bowel movement for more than 48 hoursor <3 bowel movements per week

Constipation despite laxative regimenat least 3 days

0

10

20

30

40

50

60

70

Placebo 0.15 mg/kg 0.30 mg/kg

% P

atie

nts

Hav

ing

Bow

el M

ovem

ent

Methylnaltrexone Is Active in Patients With Opioid Induced Constipation

> 50% of Patients Have Bowel MovementWithin 4 Hours (Study 301)

Recommended Dose

Methylnaltrexone Induces aRapid and Predictable Response in OIC

Recommended Dose

% P

atie

nts

Hav

ing

Bow

el M

ovem

ent

Hours

0%

25%

50%

75%

0 1 2 3 4 5

0.30 mg/kg30 minutes

0.15 mg/kg

Placebo

Study 301

Methylnaltrexone Subcutaneous Is Well Tolerated

No serious safety events related to the drug

Most common side effects

Abdominal cramping

Flatulence

Nausea

Dizziness

23 hoursFirst bowel movement (p=0.01)

25 hoursTolerance of first solid meal (p=0.12)

Acceleration Acceleration (On Average)(On Average)Time to PostTime to Post--operative Recovery Endpointoperative Recovery Endpoint

65 patients with segmental colectomies Randomized to methylnaltrexone IV or placeboEvaluated for clinical signs indicating recovery of bowel function and readiness for discharge

Methylnaltrexone IV Accelerates Recovery in Post Operative Ileus (POI)

Phase 2 Data

25 hoursActual discharge (p=0.09)

30 hoursDischarge eligibility (p=0.03)

Discharge a day earlyDischarge a day early

Methylnaltrexone Clinical Studies

NDA: Late 2007-Early 2008 in U.S.†

Ex-U.S. within1 year

Post-surgical patients

Phase 3 (Ongoing)

IntravenousIntravenous

NDA: 2008 –2009 in U.S.


NDA (for AI):Early 2007 in U.S.†


Patients with chronic pain

Expansion beyond advanced illness (AI)

Phase 2 (Adaptive) (Ongoing)

Phase 3 (Completed)

OralOralSubcutaneousSubcutaneous

† Potential for priority review

Methylnaltrexone:Future Standard for Rapid and Predictable Relief

of Opioid Side Effects

Novel approach to control of opioid side effects

Relieves constipation and allows maintenance of pain control

Phase 3 (SC) data show positive results in patients with advanced illness whose palliative care includes opioids

Phase 2 (IV) studies - positive results for post surgical recovery of bowel function

Drug was generally well tolerated

Methylnaltrexone: A New Standard in Treating Opioid Side Effects

Key Product Features

Subcutaneous – 1st in class for OICFast: ~ 30 minutes

Intravenous – 1st and only IV for POI Flexible: Post-op (Fast Track)Preferred: IV dose form

Oral – Long-term useContinuity: Methylnaltrexone familyBreadth: Studying other peripheral effects

SC – NDA Early 2007 (1st for OIC)

IV – Phase 3: File late 2007 or early 2008 (1st /only IV)

Oral – Phase 2: File late 2008 or early 2009 (OIC)

Status

> $1 Billion†Peak Sales

Development collaboration with Progenics† Wyeth estimate of worldwide combined value of the three dosage forms

Methylnaltrexone Product Profile

First multi-formulation treatmentfor peripheral opioid side effects

R&D: Innovation Continues to Fuel Wyeth’s Long-Term Growth

Robert R. Ruffolo, Jr., Ph.D.Senior Vice President, WyethPresident, Wyeth Research

Highlights from the middle of the pipeline

Oncology strategy

“War” on Alzheimer’s Disease

Key compounds from our major technology platforms

Wyeth R&D strategy: Focus on R&D productivity and innovation

Major registration submissions

Innovation Providesthe Future Pipeline

Highlights FromThe Middle of the Pipeline

SCA-171SKS-927NRI-193PPM-201PPM-202SRA-444GAP-134BLI-489SAM-610SKI-015PRA-027BHS-019CME-548AAB-002ILV-094TRU-015 (Onc)

PLA-695SAM-315SAM-531TTI-237PAI-749PAZ-417MST-997LXR-623SLV-313SLV-314PSI-697GSI-953AGG-523HIV Vaccine (4)MnB(2)ACC-001Inotuzumab

(CMC-544)IMA-638

HCV-796LecozotanPrinaberelMethylnaltrexone

(PO)PPM-204Bosutinib

(SKI-606)Vabicaserin(SCA-136)

HKI-27213vPnC AdultEnbrel – AsthmaBapineuzumabGAP-486MYO-029TRU-015 (RA)BMP-2 Inject.

Lybrel™ContinuousContraception

Pristiq™ (MDD)Viviant™ (Osteo)Pristiq™(VMS)Protonix® Ad.

GranulesBeneFIX Reform.Mylotarg® – AML

(EU)

Small MoleculesVaccinesProteins

Aprela™Torisel™ RenalTorisel™ MCLTygacil®(HAP/CAP)

Bifeprunox (Schizo)Bifeprunox (Bipolar)Pristiq™

FibromyalgiaPristiq™

(Neuropathic Pain)Methylnaltrexone

(SC)Methylnaltrexone

(IV)Lybrel™ PMDDProtonix® Oral PedRapamune® Liver13vPnC InfantReFacto® AF

Phase 0 Phase 1 Phase 2 Phase 3 Registration

Phase 016

Phase 122

Phase 215

Phase 315

Registration7

27330-9550

Wyeth Development Pipeline

Oncology Strategy

Phase 0 Phase 1 Phase 2 Phase 3

CME-548

HKI-272

Bosutinib(SKI-606)

TRU-015 MST-997

Inotuzumabozogamicin(CMC-544)

TTI-237

Registration

Wyeth Oncology Development Pipeline

Torisel™(Renal Cancer)

Mylotarg™AML – EU

Torisel™(MCL)

SKI-015


CME-548 Torisel™(Renal Cancer)

HKI-272

Bosutinib(SKI-606)

TRU-015 MST-997

Inotuzumabozogamicin(CMC-544)

TTI-237

Registration

Mylotarg™AML – EU

Wyeth Oncology Development PipelineCompounds With Early Clinical Data

Torisel™(MCL)

SKI-015

Mylotarg®

MST-997TTI-237

Cell SignalingInhibitors

Cell CycleInhibitors

Antibody-Targeted

Chemotherapy

Torisel™HKI-272Bosutinib

(SKI-606)SKI-015TRU-015

Inotuzumab(CMC-544)

Receptor

Signal

Signal

Signal

CD22CD22

CD33CD33

Anti-5T4Anti-5T4

Wyeth’sThree Oncology Strategies

CME-548

Wyeth Immunoconjugates Have the Potentialto Deliver a Lethal Hit Directly to Cancer Cells

The Strategy:Identify antigen expressed preferentially on cancer cells

Develop an antibody specificto antigen

Conjugate the antibody to calicheamicin

Tumor cells incur lethal DNA damage

= Antigen= AcBut Linker= Antibody= Calicheamicin

MylotargTargets CD33Indication: Relapsed Acute Myelogenous LeukemiaMarketed in U.S. and Japan;EU pending approvalCo-developed with UCB

Inotuzumab (CMC-544)Targets CD22Indication:Non-Hodgkins LymphomaPhase 1Co-developed with UCB

CME-548Targets Anti-5T4Indication: Solid tumorsIND December 2006

Mylotarg®, Inotuzumab (CMC-544) andCME-548 – Directed to Specific Tumor Cells

Patients with B-cell Non-Hodgkin’s Lymphoma who havedisease progression after at least 2 prior therapies

Response, nDose Level

mg/m2

66%31111.8 q4 wk10

2142

PD

50%1111.8 q3 wk44%1311.34 q3 wk

48%674OVERALL

50%0202.4 q3 wk

25%1010.8 q3 wk

OverallResponse

RateCRPRSD

Main Eligibility Criteria:

Clinical Activity Observed:

Phase 1 Clinical Trial – Inotuzumab (CMC-544)Preliminary Clinical Activity

PD = Progressive Disease; SD = Stable Disease; PR = Partial Response; CR = Complete Response

EGFEGFEGF

Tumor cell migration, invasion, metastasis

Tumor cell bioenergetics and growth

PI 3-kinasePI 3PI 3--kinasekinase

mTORmTORmTOR

AKTAKTAKT

SrcSrc

Signaling Inhibitors Target Critical Growth Pathways in Cancer Cells


EGFEGFEGF




mTORmTORmTOR

AKTAKTAKT

SrcSrc

Torisel™

Bosutinib (SKI-606)HKI-272


EGFEGFEGF




mTORmTORmTOR

AKTAKTAKT

SrcSrcBosutinib (SKI-606)

Chronic Myelogenous Leukemia Tumor Model

Bosutinib (SKI-606), a Src/Abl Kinase Inhibitor,Has Potential for Treatment of Numerous Cancers

0

1000

2000

3000

0 2 4 7 11Day

Tum

or V

olum

e (m

m3)

No Treatment

SKI-606

Solid Tumors: Patients with advanced or recurrent solid tumors who have failed standard therapy Chronic Myelogenous Leukemia: Patients who are refractory to or have relapsed after Gleevec therapy

Main Eligibility Criteria:

Clinical Activity Observed:Solid tumors: evidence of stable disease and tumor shrinkage Chronic Myelogenous Leukemia:

Responses in Gleevec-resistant patients

3 (7)

7 (7)

n(# Evaluable)Response

44%Complete cytogenetic response

100%Complete hematologic response

%

Clinical Trial Data – Bosutinib (SKI-606)Preliminary Clinical Activity


EGFEGFEGF




mTORmTORmTOR

AKTAKTAKT

SrcSrc

HKI-272

Ba/F3 cells transfected with EGFRL858R: Activating mutation conferring sensitivity to ErbB inhibitorsT790M: Mutation conferring resistance to Iressa/Tarceva

Ji et al. (2006), Proc. Natl. Acad. Sci. USA 103, 7817-7822

Breast Cancer: HKI-272, an Irreversible ErbB Inhibitor, Overcomes Resistance to Tarceva

0

25

50

75

100

125

0.001 0.01 0.1 1 10

Concentration (µM)

% C

ell V

iabi

lity

TarcevaHKI-272

23 (79)Evaluable patients

7 (24)Confirmed partial response (PR)

1 (3)Stable disease ≥ 24 wks

Number (%) n = 29Tumor Response

24% response rate in breast cancer patientsDuration of PR for breast cancer patients: 7.3 – 23.9 weeks

Patients with advanced erbB-1 (EGFR)- or erbB-2 (HER2)-positive(1+ to 3+) breast cancer who failed standard therapy

Main Eligibility Criteria (Breast Cancer):


Phase 1 Clinical Trial:HKI-272 Preliminary Clinical Activity

November 2005 March 2006

Pre-treatment 17 Weeks of HKI-272

Phase 1 Study- HKI-272 Preliminary Clinical Activity (Breast Cancer Patient)


EGFEGFEGF




mTORmTORmTOR

AKTAKTAKT

SrcSrc

Torisel™

Phase 3 randomized, controlled study in MCL ongoingNDA submission planned for 2007

Over-expression of cyclin D1, which is regulated by mTORMantle Cell Lymphoma (MCL):

2734Evaluable patients, n4138Overall response rate, %

6.56.9Duration of response, months5.56.5Median TTP, months1112Median survival, months

Temsirolimus Dose(mg/week)

25 mg250 mg

Patients with relapsed or refractory, advanced MCLMain Eligibility Criteria:

Phase 2 Clinical Trial – Torisel™(NCI/CTEP Collaboration)


Status:

Mylotarg®

MST-997TTI-237

Cell SignalingInhibitors

Cell CycleInhibitors

Antibody-Targeted

Chemotherapy

Torisel™HKI-272Bosutinib

(SKI-606)SKI-015TRU-015

Inotuzumab(CMC-544)

Receptor

Signal

Signal

Signal

CD22CD22

CD33CD33

Anti-5T4Anti-5T4

Wyeth’s Three Oncology Strategies

CME-548

Alzheimer’s Disease Strategy:“War” On Alzheimer’s Disease

A devastating neurological disease that impacts the lives of patients, families, caregivers and societyCurrently affects >24 million people worldwide

Expected to reach 80 million by 2040Accounts for >60% of all dementiasPrevalence is 1% between the ages of 60-64but increases exponentially to 33% in peopleaged over 85

In later stages of the disease, patients require full-time careDirect and indirect costs are estimated to be in excessof $100 billion/yearWyeth has mounted a “War” against Alzheimer’s Disease

Alzheimer’s Disease

Current Alzheimer’s Treatments Are Relatively Poor and Do Not Address the Disease Process

Current Treatments

Marginal and symptomatic

Future Treatments

Slow disease progressionand produce greater

improvementsin cognitive function

Cholinesterase Inhibitors

NMDA Receptor Antagonists


SLV-313

ACC-001

SCA-171

SAM-315

SAM-531

Vabicaserin (SCA-136)

Lecozotan(Alzheimer’sDisease)

Bapineuzumab(Alzheimer'sDisease)

PAZ-417

AAB-002

SRA-444

SLV-314

GSI-953

SAM-610

Pristiq™(Depression)

Bifeprunox(Schizophrenia)

SKS-927

Wyeth Neurosciences Development Pipeline

Pristiq™(Neuropathic Pain)

Pristiq™(Fibromyalgia)

Bifeprunox(BipolarDisorder)

Effexor XR Japan

Registration


SLV-313

ACC-001

SCA-171

SAM-315

SAM-531

Vabicaserin (SCA-136)

Lecozotan(Alzheimer’sDisease)

Bapineuzumab(Alzheimer'sDisease)

PAZ-417

AAB-002

SRA-444

SLV-314

GSI-953

Wyeth Neurosciences Development Pipeline

Registration

Pristiq™(Depression)

Bifeprunox(Schizophrenia)

Pristiq™(Neuropathic Pain)

Pristiq™(Fibromyalgia)

Bifeprunox(BipolarDisorder)

Effexor XR Japan

SAM-610

SKS-927

Alzheimer’s Disease Strategy

GSI-953GSI-953Phase 1Phase 1

PAZ-417PAZ-417Phase 1Phase 1

LecozotanPhase 2

SAM-315Phase 1

BapineuzumabBapineuzumabPhase 2Phase 2

AAB-002AAB-002Phase 0Phase 0

ACC-001ACC-001Phase 1Phase 1

BiologicsBiologics OralOral

Disease ModifiersDisease Modifiers

Oral: Enhanced Cognition

SymptomaticsSymptomatics

Patients TreatedPatients Treated

May be usedin combination

Elan Alliance

SAM-610Phase 0

SAM-531Phase 1

SRA-444Phase 0

Vaccines Proteins Small Molecules

Wyeth’s Alzheimer’s Program UtilizesAll Three Technology Platforms

ACC-001† LecozotanGSI-953PAZ-417SAM-531SAM-315SRA-444SAM-610

Bapineuzumab†

AAB-002†

Alzheimer’s Disease

† Alliance with Elan

Neuropathology Leading to Cognitive

Dysfunction

AβAmyloid Protein

β-Amyloid Deposits

Beta Secretase Gamma Secretase

Beta Amyloid Peptide

Aβ

Inhibition of the Amyloid Pathway


Dysfunction

AβAmyloid Protein



Aβ

ACC-001 (Active Immunization)

Clearance from Brain Resulting in Neuroprotection

Inhibition of the Amyloid PathwayTherapeutic Vaccine: Plaque Removal

β-Amyloid Deposits


Dysfunction

AβAmyloid Protein



Aβ

Clearance from Brain Resulting in Neuroprotection

BapineuzumabAAB-002(Passive Immunization)

Inhibition of the Amyloid PathwayPlaque Removal

β-Amyloid Deposits

Bapineuzumab (AAB-001), AAB-002 and ACC-001

From Immunotherapy alliance with ElanGoal: To clear brain Aβ and prevent or reverse AD disease progressionEffective in reducing plaque in animal models

Clinical status:Bapineuzumab – Phase 2ACC-001 – Phase 1AAB-002 – Phase 0

Alzheimer’s Disease: Immunotherapy Program Targeting Disease Progression

mAb 3D6 (Parent of AAB-001)

Aβ Plaques

Control

YesYes NoNo

Phase 2 Multiple Ascending Dose Study Ongoing~60 patients receive drug or placebo in each of fourdose cohortsDoses given every 3 months with last dose at 15 monthsAmyloid-PET imaging data being obtained

Next interim decision point (4Q06): Decision to initiate Phase 3 studies

Phase 3 begins1H2007

Proceed to interim look in 1H2007

BapineuzumabPhase 2 Status

Bapineuzumab SAD Study: MMSE Reveals a Trend Toward Cognitive Improvement at 4 Months and 1 Year

*p=0.047 vs pbo

1 Year MMSE Change From Baseline

-4%

-2%

0%

2%

4%

0 0.5 1.5 5.0

Month 4 MMSE Change From Baseline

-4%

-2%

0%

2%

4%

0 0.5 1.5 5.0MM

SE C

hang

e Fr

om B

asel

ine

+/-

SEM

*

Dose (mg/kg)


Dysfunction

AβAmyloid Protein

β-Amyloid Deposits



Aβ

PAZ-417(Plasminogen Activator Inhibitor)

Inhibition of the Amyloid PathwayPrevention of Plaque Formation


Dysfunction

AβAmyloid Protein

β-Amyloid Deposits



Aβ

GSI-953 (Gamma Secretase Inhibitor)

Inhibition of the Amyloid PathwayPrevention of Plaque Formation


Dysfunction

AβAmyloid Protein

β-Amyloid Deposits



AβLecozotanSRA-444SAM-315SAM-531SAM-610

Inhibition of the Amyloid PathwayCognitive Improvement

-0.70

0.19

1.56

-0.43

-1.8 -1.77

-2

-1

0

1

2Placebon=15

0.5mg BIDn=6

1mg BIDn=6

2.5mg BIDn=6

5mg BIDn=12

10mg QDn=11

Mea

n C

hang

e Fr

om B

asel

ine

LS Mean ±SE: -0.70±1.21 0.19±1.91 1.56±1.91 -0.43±1.91 -1.80±1.36 -1.77±1.41

Lecozotan Has Been Given to Mild-to-Moderate AD Patients in Phase 1 StudiesMean Change in ADAS-Cog from Baseline: Disease Severity Score

LecozotanSRA-444SAM-315SAM-531SAM-610


Dysfunction

AβAmyloid Protein

β-Amyloid Deposits



AβPAZ-417(Plasminogen Activator Inhibitor)

GSI-953 (Gamma Secretase Inhibitor)

ACC-001(Active Immunization)

BapineuzumabAAB-002(Passive Immunization)

“War” on Alzheimer’s Disease

Alzheimer’s Disease Strategy

GSI-953GSI-953Phase 1Phase 1

PAZ-417PAZ-417Phase 1Phase 1

LecozotanPhase 2

SAM-315Phase 1

BapineuzumabBapineuzumabPhase 2Phase 2

AAB-002AAB-002Phase 0Phase 0

ACC-001ACC-001Phase 1Phase 1

BiologicsBiologics OralOral

Disease ModifiersDisease Modifiers

Oral: Enhanced Cognition

SymptomaticsSymptomatics

Patients TreatedPatients Treated

May be usedin combination

Elan Alliance

SAM-610Phase 0

SAM-531Phase 1

SRA-444Phase 0

Examples From Wyeth’sThree Technology Platforms

Vaccines

MnB

Small Molecules

HCV-796

Proteins

TRU-015

Collaboration with ViroPharma

Directed against Hepatitis C polymerase

Status of development: Phase 2B

Indication: Hepatitis C

Efficacy: Ability to reduce viral load

Potentiation with other agents for Hepatitis C

HCV-796

Hepatitis C Burden to Patients and Health Care Systems

Estimate of 170 million people infected worldwideThe most common long-term, blood-borne infection in the U.S. – 4 times that of HIV

2.7 million have long-term infectionClinical consequences:

Cirrhosis, liver cancer, liver failure (leading to transplant)70% of infected patients develop liver diseaseHCV responsible for 1/3 of all liver transplants

Costs associated with HCVNon-transplant HCV patients: ~$100,000over lifetimeLiver transplant: ~$280,000/first year costs alone

Source: Decision Resources, 12/2004; Koop Institute; CDC

HCV-796 Plus PEG-Intron Phase 1 Study: Results Support Advancement to Phase 2

At day 14, 30% of patients in the combination group achievedviral levels below the level of quantitation

HCV-796(500 mg BID)

Peginterferon

Combination

Study Day

-3.5

-3

-2.5

-2

-1.5

-1

-0.5

0

7 14

Ch

ange

in H

CV

RN

A

(log

IU

/ml)

MnB Vaccine: Meningococcal Disease

Infection caused by Neissera meningitidis belonging to five serogroups: A, B, C, Y, W-135

Invasive disease progression is rapid and associated with high mortality (10%)

Invasive disease is most prevalent among young children and adolescents

Effective polysaccharide conjugate vaccines are available, or under development, for types A, C, Y and W-135

A polysaccharide vaccine for type B is not possible

Distribution of Meningococcal Serogroups –All Age Groups

U.S. and EU (1999-2000)Type B accounts for one-third of Mn disease in

the U.S., and two-thirds of Mn disease in the EU

BB BBAll OthersAll Others

U.S. EU

SBA (Serum Bactericidal Antibody) From Immunized Cynomolgus Macaques

Meningococcal B Vaccine –Strain 870446 – Subfamily A

Monkey Pre-Bleed Week 8 Bleed Week 12 Bleed1357 16 1186 8532734 5 1938 2653725 5 224 482407 <4 221 962403 <4 320 56

Serum Bactericidal Activity Titer

Titer of 1:8 protective against meningococcal diseaseClinical status: Phase 1

Exclusive license from Trubion Pharmaceuticals, Inc.A new drug and a new platform:

Small Modular Immunopharmaceutical Proteins (SMIP™) TRU-015 is a SMIP directed against CD-20

Status of development: Phase 2B initiatedPotential indications: Rheumatoid arthritis, lupus and oncologyPotential advantages over Rituxan:

Shorter duration of B-cell depletionBetter tolerabilityMore convenient dosing

TRU-015

SMIP

CH2

CH3

V HV L

~100KDa

Antibody

~150KDa

C L

C H1

CH2

CH3

V H

V L

What Is A SMIP™? A Unique Scaffold; And it Works

TRU-015Clinical Program

Phase 1/2A – Single IV dose; retreatment regimen has initiated

TRU-015 is well toleratedPhase 2A

36 subjects with active RA on methotrexate10 active:2 placebo per cohort 5 mg/kg (x1), 2.5 mg/kg (x2), 7.5 mg/kg (x2)B cell depletion observed in all cohortsProof-of-principle established

Meaningful clinical benefit observedPhase 2B initiated

TRU-015 Phase 2A Protocol 15001Clinical Response Achieved at 12 Weeks

Compared to Rituximab65%

33%

15%

Rituximab(DANCER; RF+ Subjects;1 gm x 2 IV; 24 Weeks)

ACR 20

ACR 50

ACR 7052%

63%

24%

38%

19%

12%

0

10

20

30

40

50

60

70

All Subjects Rheumatoid Factor + Subjects

TRU-015

Per

cen

t R

espo

nse

R&D Productivity

Metrics and objectives

Accountability and alignment

Linked compensation to performance

Balanced score cards

Standardized compound requirements for Discovery and Development

R&D Productivity Model

The pipeline has grown in breadth, depthand innovation

Innovation Outside the Laboratory: Changes Implemented in R&D 6 Years Ago

Wyeth R&D Productivity Model

12 Compounds Entering Development

⇓ 70% Success Rate*

8 INDs Submitted


3 Compounds Reach Phase 3


2 Major NDAs Submitted per Year

Target

* Standard Pharmaceutical Industry Success Rates in 2000

Revised R&D Productivity ModelInstituted in 1Q06

15 Compounds Entering Development

⇓ 80% Success Rate (was 70%)

12 INDs Submitted


3 Compounds Reach Phase 3


2 Major NDAs Submitted per Year

Target

How Did We Perform Against theWyeth R&D Productivity Model?

Target 1990-2000 2001 2002 2003 2004 2005 2006T

12 Development Track Cpds 3 12 12 12 12 12 15⇓ 70% Success Rate

8 INDs Submitted 1.5 8 11 12 9 8 12⇓ 40% Success Rate

3 Cpds Reach Phase 3 0.3 1 1 3 2 2 3⇓ 60% Success Rate

2 Major NDAs Submitted per Year 0 0 0 1 2 4

We are now achieving our target of submitting 2 major NDAs/year

Increase efficiency

Increase quality

Reduce costs

Reduce cycle times

Improve consistency

Increase success rates

Improve decision-making

Changing theClinical Development Paradigm

New Changes in How We Do Clinical Trials

Learn and confirm teams rolled out; training in placeLearn & Confirm

New governance in placeGovernance

Comprehensive data standards for all programs

100% of protocols optimized for cost

Pipeline of adaptive studies under development

24x7 center in Bangalore; 1Q’07 launch

DHL will be primary logistics partner

>90% of new studies will be utilizing RDC

Improvements in study planning & execution

100% of studies optimized for global patient mix

10 ECDCs will be established by year-end

Data standards

Cost optimization tool

Adaptive trials

24x7

Clinical Materials Management

Remote Data Capture

Clinical Trial Enrollment

Global Patient Recruitment

Early Clinical Development Centers (ECDCs)

Shift From a Phased Development to a “Learn and Confirm” Paradigm

Phase 2

From today’s phased approach …IND POC NDA Submission

Phase 1Phase 1 Phase 2Phase 2 Phase RPhase R

Transition time

Phase 3Phase 3

Shift From a Phased Development to “Learn and Confirm” Paradigm

… to Learn and Confirm

Phase RPhase RLearn Confirm

Transition Zone

IND NDA SubmissionPOC

ConfirmLearn

Shifting Global Patient Recruitment Mix to Improve Clinical Trial Enrollment

50%50%

15%15%

20% / 10%20% / 10%

5%5%

Current Patient Mix

30%30%

20%20%

5% / 20%5% / 20%

25%25%

New Patient Mix (2006)

Shift global recruiting mix for clinical trialsMeeting global regulatory needsPotential for significant cost savingsPotential for significant time savingsTarget 70% ex-NA new trials by end of 2006

Establishing Early Clinical Development Centers (ECDCs) to Enhance POC

Phase 2 “Supercenters” located in areas of high patient densityGoal: 10-15 ECDC “Supercenters” for 80% of all Learnpatient recruitmentApproximately 10 ECDCs targeted by the end of 2006ECDCs – more consistency; better quality control and efficiency

Latin AmericaLatin AmericaIndiaIndia

China/HKChina/HKE. EuropeE. Europe

U.S.U.S.

Key Registration Submissions

Pristiq™ (Depression)

Viviant™ (Osteoporosis Prevention)

Pristiq (Vasomotor Symptoms)

Lybrel™ (Continuous Contraception)

Protonix® Adult Granules

BeneFIX® Reformulation

Compounds Submitted for Registration and Awaiting FDA Approval

Bifeprunox (Schizophrenia)

Torisel™ (Renal Cell Cancer)

Effexor® (Japan)

Significant Registration Submissionsto Be Filed in 4Q06

Aprela™ (Osteoporosis/Vasomotor Symptoms)

Viviant™ (Osteoporosis Treatment)

Tygacil® (HAP/CAP)

Methylnaltrexone-SC (Opioid Induced Constipation –Advanced Illness)

Methylnaltrexone-IV (Post Operative Ileus)

Torisel™ (Mantle Cell Lymphoma)

ReFacto® AF

Prevnar® (Japan)

Tygacil (Japan)

Viviant (Japan)

Major Regulatory SubmissionsPlanned For 2007

Pristiq™ (Neuropathic Pain)

Pristiq (Fibromyalgia)

Methylnaltrexone Oral(Opioid-Induced Constipation)

Rapamune® (Liver Conversion)

Lybrel™ (Premenstrual Dysphoric Disorder)

Major Regulatory SubmissionsPlanned For 2008

TRU-015(Rheumatoid Arthritis)

13vPnC (Adult)

13vPnC (Infant)

Bosutinib (SKI-606) (Oncology)

Bapineuzumab(Alzheimer’s Disease)

CMC-544 (NHL)

HCV-796 (Hepatitis C)

IMA-638 (Asthma)

Lecozotan(Alzheimer’s Disease)

MYO-029(Muscular Dystrophy)

SCA-136 (Depression)

HKI-272 (Oncology)

Major Regulatory SubmissionsNext Wave

Summary

The pipeline has grown in breadth, depth and innovation at all phases

There are more NMEs in all stages of development; these represent >75%of the pipeline

Our Phase 3 pipeline and NDA submissions remain strong

Conclusion

Bernard PoussotPresident and Vice Chairman, Wyeth


Growth of In-Line Products

Incremental Revenue Potential

Enbrel®

Tygacil®

Prevnar®

Greater Than $1 Billion




13v PnC - Adult

Pristiq™

Aprela™/Viviant™

Methylnaltrexone

Greater Than$1 Billion

$500 Million -$1 Billion $250 Million

Torisel™

Bifeprunox

Lybrel™





Operational Excellence





Improved Manufacturing Efficiencies






Strong R&D






Strong R&D

Wyeth is positioned to bea stronger company

at the end of the decadeand enter the next decade with

great momentum.

Economy & Finance

wyeth 2006 Analysts Meeting Presentation