wyeth 2006 analysts meeting presentation
TRANSCRIPT
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Welcome
Justin R. VictoriaVice President, Investor Relations
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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.
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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.
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Introduction
Robert EssnerChairman and Chief Executive Officer, Wyeth
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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
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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
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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
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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
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Wyeth Future Growth Prospects
In-Line Product Growth
Portfolio of New Product Opportunities
Productivity Improvements
Broad-Based Research
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Wyeth is positioned to bea stronger company
at the end of the decadeand enter the next decade with
great momentum.
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Enbrel®(Etanercept)
Ulf WiinbergSenior Vice President, Wyeth
President, Wyeth Pharmaceuticals - EMEA
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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
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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%
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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
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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
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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
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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
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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)
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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
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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.
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Trend Towards Earlier Treatment
Recent-Onset RA
Severely-Advanced RA
Moderately-Advanced
RA
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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
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Convenience
Pre-filled Syringe 25mg/50mg
Autoinjector
Patient Services
The flexibility of 3 administration options
NEW!NEW!
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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
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Grange Castle … Wyeth’s Commitment to Biotech Growth
4 Integrated Manufacturing Facilities
Drug Substance
Vaccine Conjugation
Fill / Finish
Syringe Line MNTX
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Prevnar®Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein)
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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
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$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®
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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)
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Bacteremia
Pneumonia
Otitis Media
Meningitis
Major Pneumococcal Diseases
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Adults dieevery yearAdults dieevery year
.5M.5M
The Face ofPneumococcal Disease
1MInfants dieevery yearInfants dieevery year
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#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
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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 ® …
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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
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$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
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Prevnar®
Launched in 70 CountriesLaunched in 70 Countries
Additional 13 launchesby 2008
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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
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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
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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
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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)
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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:
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13-Valent Pneumococcal PolysaccharideConjugate Vaccine
(13v PnC)
Emilio A. Emini, Ph.D., F.A.A.M.Executive Vice President
Vaccine Research and Development
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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
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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.
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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
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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
(Children <5 Years of Age)
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
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7v vs 10v vs 13v Serotype Coverage Comparison – U.S.
Pre-Prevnar® (1998) 81%
7v
Post-Prevnar (2003) 17%
Prevnar has greatly reduced serious disease caused by the7 vaccine-associated serotypes
Source: CDC ABC Surveillance
13v PnC ProvidesSuperior Coverage in the U.S.
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7v vs 10v vs 13v Serotype Coverage Comparison – U.S.
10v
81%
7v
Post-Prevnar (2003) 17% 22%
A 10v vaccine provides only marginal additional coverage
13v PnC ProvidesSuperior Coverage in the U.S.
Prevnar has greatly reduced serious disease caused by the 7 vaccine-associated serotypes
Pre-Prevnar® (1998)
Source: CDC ABC Surveillance
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7v vs 10v vs 13v Serotype Coverage Comparison – U.S.
13v10v
81%
7v
Post-Prevnar (2003) 17% 22% 60%
13v PnC will provide substantial coverage
13v PnC ProvidesSuperior Coverage in the U.S.
A 10v vaccine provides only marginal additional coverage
Prevnar has greatly reduced serious disease caused by the7 vaccine-associated serotypes
Pre-Prevnar® (1998)
Source: CDC ABC Surveillance
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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
![Page 52: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/52.jpg)
33
6A6A
19A19A
13v PnC13v PnC
7F7F
11
55
Serotype Coverage Prevnar® (7v) and 13v PnC
444
1414149V9V9V 18C18C18C
23F23F23F19F19F19F
6B6B6BPrevnarPrevnar
![Page 53: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/53.jpg)
Serotype Coverage Prevnar® (7v) and 13v PnC
444
1414149V9V9V 18C18C18C
23F23F23F19F19F19F
6B6B6BPrevnarPrevnar
GSK 10vGSK 10v33
6A6A
19A19A
13v PnC13v PnC
7F7F
11
55
19A19A
![Page 54: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/54.jpg)
Pai R. JID. 2005;192:1988-95.
Incidence of Invasive Pneumococcal Disease Due to Serotype 19A in the U.S.
(Children <5 Years of Age)
0
1
2
3
4
5
6
7
July 1999 –June 2000
July 2000 –June 2001
July 2001 –June 2002
July 2002 –June 2003
July 2003 –June 2004
Rat
e (C
ases
/10
0,0
00
Pop
ula
tion
)
Time
![Page 55: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/55.jpg)
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
![Page 56: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/56.jpg)
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
![Page 57: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/57.jpg)
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
![Page 58: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/58.jpg)
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
![Page 59: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/59.jpg)
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
![Page 60: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/60.jpg)
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
![Page 61: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/61.jpg)
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
![Page 62: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/62.jpg)
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
![Page 63: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/63.jpg)
23v Ps23v Ps
7v7v PnCPnC7v7v PnCPnC
7v7v PnCPnC23v Ps23v Ps
Year 1 Year 2
Is the Antibody Response to 7v PnC Equivalent/ Superior to the 23v Ps Response?
![Page 64: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/64.jpg)
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
![Page 65: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/65.jpg)
23v Ps23v Ps
7v7v PnCPnC7v7v PnCPnC
7v7v PnCPnC23v Ps23v Ps
Year 1 Year 2
Does Prior 23v Ps Immunization Affect the Responseto Subsequent 7v PnC Immunization?
![Page 66: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/66.jpg)
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
![Page 67: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/67.jpg)
23v Ps23v Ps
7v7v PnCPnC7v7v PnCPnC
7v7v PnCPnC23v Ps23v Ps
Year 1 Year 2
Does Prior 7v PnC Immunization Blunt the Responseto a Second Dose of 7v PnC?
![Page 68: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/68.jpg)
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
![Page 69: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/69.jpg)
Does Prior 7v PnC Immunization Affect the Response to Subsequent 23v Ps Immunization?
23v Ps23v Ps
7v7v PnCPnC7v7v PnCPnC
7v7v PnCPnC23v Ps23v Ps
Year 1 Year 2
![Page 70: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/70.jpg)
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
![Page 71: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/71.jpg)
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
![Page 72: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/72.jpg)
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
![Page 73: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/73.jpg)
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
![Page 74: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/74.jpg)
![Page 75: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/75.jpg)
New Product Opportunities
Joe MahadySenior Vice President, Wyeth
President, Wyeth Pharmaceuticals,The Americas and Global Businesses
![Page 76: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/76.jpg)
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
)
![Page 77: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/77.jpg)
Pristiq™ (DVS-233)(Desvenlafaxine Succinate)
![Page 78: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/78.jpg)
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
![Page 79: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/79.jpg)
Pristiq™ Differentiation
With FDA-approval, the firstnon-hormonal treatment of moderate-to-severe vasomotor symptoms (VMS)
associated with menopause
With FDA-approval, the firstnon-hormonal treatment of moderate-to-severe vasomotor symptoms (VMS)
associated with menopause
![Page 80: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/80.jpg)
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
![Page 81: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/81.jpg)
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
![Page 82: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/82.jpg)
Pristiq™(Desvenlafaxine Succinate)
With FDA-approval, the firstnon-hormonal treatment of moderate-to-severe vasomotor symptoms (VMS)
associated with menopause
With FDA-approval, the firstnon-hormonal treatment of moderate-to-severe vasomotor symptoms (VMS)
associated with menopause
![Page 83: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/83.jpg)
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
![Page 84: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/84.jpg)
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%
![Page 85: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/85.jpg)
Initially Approached Two Distinct Products
Depression Vasomotor Symptoms
Product A Product B
![Page 86: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/86.jpg)
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
![Page 87: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/87.jpg)
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
![Page 88: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/88.jpg)
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
![Page 89: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/89.jpg)
Pristiq™(Desvenlafaxine Succinate)
Ginger Constantine, M.D.Vice President and Therapeutic Area Director
Woman’s Health and Bone RepairClinical Research & Development,
Wyeth Pharmaceuticals
![Page 90: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/90.jpg)
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
![Page 91: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/91.jpg)
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
![Page 92: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/92.jpg)
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
![Page 93: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/93.jpg)
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
![Page 94: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/94.jpg)
*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
![Page 95: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/95.jpg)
Pristiq™(Desvenlafaxine Succinate)
Efficacy on Major Depressive DisordersMen & Women
![Page 96: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/96.jpg)
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
![Page 97: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/97.jpg)
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
![Page 98: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/98.jpg)
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
HAM-D Δ from Baseline
* Statistically significant - p <.05 vs placebo
Pristiq™: Effective in MDD 100 mg - 400 mg/Day
Placebo-Controlled Studies
![Page 99: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/99.jpg)
HAM-D Δ from Baseline
Effexor XR® Comparator
317
309
*
Placebo
Placebo
Pristiq 200-400 mg
Pristiq 200-400 mg
Effexor XR® 75-150 mg
Effexor XR® 150-225 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
* Statistically significant - p <.05 vs placebo
Placebo-Controlled Studies
Pristiq™: Effective in MDD 100 mg - 400 mg/Day
![Page 100: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/100.jpg)
Primary Efficacy Variable (HAM-D17) Mixed Effects Model – Week 8
* p-value vs placebo ≤ 0.05
HAM-D Δ from Baseline
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
Effexor XR® 75-150 mg
Effexor XR® 150-225 mg
Pristiq 100 mg
-20
*
*
*
306
308
![Page 101: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/101.jpg)
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
![Page 102: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/102.jpg)
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
![Page 103: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/103.jpg)
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
![Page 104: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/104.jpg)
Pristiq™(Desvenlafaxine Succinate)
Efficacy on Vasomotor Symptoms
![Page 105: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/105.jpg)
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
![Page 106: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/106.jpg)
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
![Page 107: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/107.jpg)
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
![Page 108: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/108.jpg)
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
![Page 109: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/109.jpg)
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
![Page 110: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/110.jpg)
Rapid Onset of Action
* p-value versus placebo <0.001
0
5
10
15
20
25
30
Tim
e in
Day
s
* * * *
Placebo Pristiq™100 mg
Pristiq150 mg
Placebo Pristiq100 mg
Pristiq150 mg
Study 315 Study 319
Time (Days) to Reach a 50% Reduction in Number of VMS
![Page 111: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/111.jpg)
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
* *
* **
Placebo Pristiq™100 mg
Pristiq150 mg
Placebo Pristiq100 mg
Pristiq150 mg
Study 315 Study 319
![Page 112: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/112.jpg)
-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
* *
*** * * *
™
![Page 113: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/113.jpg)
Pristiq™(Desvenlafaxine Succinate)
Safety/Tolerability Profile
![Page 114: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/114.jpg)
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
![Page 115: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/115.jpg)
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
†
![Page 116: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/116.jpg)
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
![Page 117: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/117.jpg)
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
™
![Page 118: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/118.jpg)
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
![Page 119: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/119.jpg)
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
![Page 120: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/120.jpg)
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
![Page 121: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/121.jpg)
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)
![Page 122: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/122.jpg)
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
![Page 123: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/123.jpg)
Pristiq™(Desvenlafaxine Succinate)
![Page 124: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/124.jpg)
Pristiq™ Will Broadenthe Reach of Our SNRI Franchise
Green = Effexor XR®
MajorDepressive
Disorder
MajorDepressive
Disorder
PanicDisorder
PanicDisorder
SocialAnxietyDisorder
SocialAnxietyDisorder
GeneralizedAnxietyDisorder
GeneralizedAnxietyDisorder
![Page 125: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/125.jpg)
Pristiq™ Will Broadenthe Reach of Our SNRI Franchise
Green = Effexor XR®
Blue = Pristiq™
Red = Effexor/PristiqPanic
DisorderPanic
Disorder
SocialAnxietyDisorder
SocialAnxietyDisorder
GeneralizedAnxietyDisorder
GeneralizedAnxietyDisorder
VasomotorSymptoms ofMenopause
VasomotorSymptoms ofMenopause
FibromyalgiaSyndrome
FibromyalgiaSyndrome
MajorDepressive
Disorder
MajorDepressive
Disorder
![Page 126: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/126.jpg)
MDD NDA Dec 2005
VMS NDA June 2006Status
> $2 BillionPeak Sales
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
![Page 127: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/127.jpg)
Viviant™/Aprela™(Bazedoxifene)
and (Bazedoxifene/Conjugated Estrogens)
Alliance with Ligand Pharmaceuticals
![Page 128: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/128.jpg)
Effective osteoporosis agent
Less potential to exacerbate hot flushes
Safe for breast and uterus
Minimal metabolic disturbances
Initial Target ProfileViviant™ (Bazedoxifene)
![Page 129: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/129.jpg)
Effective osteoporosis agent
Less potential to exacerbate hot flushes
Safe for breast and uterus
Minimal metabolic disturbances
Evolving Target ProfileViviant™ (Bazedoxifene)
![Page 130: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/130.jpg)
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
![Page 131: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/131.jpg)
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
![Page 132: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/132.jpg)
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
![Page 133: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/133.jpg)
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
![Page 134: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/134.jpg)
Aprela™(Bazedoxifene/Conjugated Estrogens)
The First TSEC or Tissue Selective Estrogen Complex
The First TSEC or Tissue Selective Estrogen Complex
![Page 135: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/135.jpg)
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™(Bazedoxifene/Conjugated Estrogens)
![Page 136: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/136.jpg)
Aprela™: The Most Comprehensive Medicine for Menopause
TSEC
BreastBreast
EndometriumEndometriumBoneBone
VaginaVagina
VasomotorVasomotor
![Page 137: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/137.jpg)
Aprela™ and Viviant™(Bazedoxifene/Conjugated Estrogens)
and (Bazedoxifene)
Ginger Constantine, M.D.Vice President and Therapeutic Area Director
Woman’s Health and Bone RepairClinical Research & Development,
Wyeth Pharmaceuticals
![Page 138: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/138.jpg)
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
![Page 139: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/139.jpg)
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
![Page 140: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/140.jpg)
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
![Page 141: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/141.jpg)
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
![Page 142: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/142.jpg)
Osteoporosis
![Page 143: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/143.jpg)
Baseline 1 Year
Architectural Change One Year Postmenopause
Borah, et al; Dufresne, et al; Abstracts presented: OI World Congress on Osteoporosis, 2002.
![Page 144: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/144.jpg)
Aprela™(Bazedoxifene/Conjugated Estrogens)
Tissue Selective Estrogen Complex (TSEC)A New Paradigm for Menopausal Therapy
![Page 145: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/145.jpg)
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
![Page 146: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/146.jpg)
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
![Page 147: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/147.jpg)
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
![Page 148: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/148.jpg)
Tissue Selective Estrogen Continuum Defines Activity
17β-EstradiolBazedoxifene
Raloxifene
Anti-Estrogens
Estrogen Receptor
FullAntagonist
FullAgonist
TSECAprela™
![Page 149: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/149.jpg)
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
![Page 150: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/150.jpg)
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
![Page 151: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/151.jpg)
Aprela™(Bazedoxifene/CE)
A New Paradigm
Relieve vasomotor symptoms
Prevent osteoporosis
Improve vulvovaginal atrophy (VVA)
Excellent amenorrhea
No increased breast tenderness vs placebo
Provide endometrial protection
Improve quality-of-life
![Page 152: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/152.jpg)
-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
![Page 153: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/153.jpg)
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
![Page 154: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/154.jpg)
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
Baseline Month 6 Month 12 Month 18 Month 24
-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
![Page 155: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/155.jpg)
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
![Page 156: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/156.jpg)
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
![Page 157: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/157.jpg)
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
![Page 158: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/158.jpg)
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
![Page 159: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/159.jpg)
Viviant™ (Bazedoxifene)
Prevention & Treatment of Osteoporosis
![Page 160: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/160.jpg)
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
™
![Page 161: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/161.jpg)
-2.00
-1.00
0.00
1.00
Baseline Month 6 Month 12 Month 18 Month 24
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
![Page 162: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/162.jpg)
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
![Page 163: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/163.jpg)
ConclusionsAprela™ and Viviant™
Aprela(Bazedoxifene/CE )
Viviant(Bazedoxifene)
Vasomotor Symptoms
Vulvovaginal Atrophy
Osteoporosis Prevention
Osteoporosis Prevention
Osteoporosis Treatment
TSEC SERM
Comprehensive Menopausal Therapy
![Page 164: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/164.jpg)
The First TSEC or Tissue Selective Estrogen Complex
The First TSEC or Tissue Selective Estrogen Complex
Aprela™(Bazedoxifene/Conjugated Estrogens)
![Page 165: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/165.jpg)
The Most ComprehensiveMedicine for Menopause
The Most ComprehensiveMedicine for Menopause
Aprela™(Bazedoxifene/Conjugated Estrogens)
![Page 166: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/166.jpg)
Vasomotor relief
Relief of vulvovaginal symptoms
Prevent osteoporosis
Achieving amenorrhea
Endometrial protection without progestin
Free of restriction on duration of use
Aprela™ Proposed Profile The Most Comprehensive Medicine for Menopause
![Page 167: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/167.jpg)
The Next Generation ofMenopausal Therapy
Viviant NDA June 2006Aprela NDA Late 2007
Status
> $2 BillionPeak Sales
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
![Page 168: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/168.jpg)
Lybrel™(90 µg Levonorgestrel/20 µg Ethinyl Estradiol)
![Page 169: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/169.jpg)
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
![Page 170: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/170.jpg)
Lybrel™(90 µg Levonorgestrel/20 µg Ethinyl Estradiol)
Ginger Constantine, M.D.Vice President and Therapeutic Area Director
Woman’s Health and Bone RepairClinical Research & Development,
Wyeth Pharmaceuticals
![Page 171: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/171.jpg)
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
![Page 172: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/172.jpg)
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
![Page 173: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/173.jpg)
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
![Page 174: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/174.jpg)
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
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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
![Page 176: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/176.jpg)
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
![Page 177: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/177.jpg)
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
![Page 178: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/178.jpg)
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
![Page 179: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/179.jpg)
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
![Page 180: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/180.jpg)
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.
![Page 181: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/181.jpg)
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
![Page 182: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/182.jpg)
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
![Page 183: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/183.jpg)
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
**
**
**
![Page 184: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/184.jpg)
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
** *
![Page 185: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/185.jpg)
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
![Page 186: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/186.jpg)
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
![Page 187: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/187.jpg)
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
![Page 188: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/188.jpg)
Lybrel™ Conclusion
Lybrel is a novel, continuous use oral contraceptive that provides:
Contraceptive efficacy
Inhibition of menses
Control of cycle related symptoms (CRS)
![Page 189: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/189.jpg)
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
![Page 190: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/190.jpg)
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
![Page 191: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/191.jpg)
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
![Page 192: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/192.jpg)
Torisel™(Temsirolimus)
![Page 193: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/193.jpg)
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
![Page 194: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/194.jpg)
Help Renal Cell Cancer PatientsLive Longer and Feel Better
Help Renal Cell Cancer PatientsLive Longer and Feel Better
Torisel™(Temsirolimus)
![Page 195: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/195.jpg)
Torisel™(Temsirolimus)
Joseph Camardo, M.D.Senior Vice President
Global Medical Affairs and North American Medical Director, Wyeth Pharmaceuticals
![Page 196: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/196.jpg)
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
![Page 197: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/197.jpg)
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
![Page 198: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/198.jpg)
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
![Page 199: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/199.jpg)
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
![Page 200: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/200.jpg)
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
![Page 201: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/201.jpg)
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
![Page 202: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/202.jpg)
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
![Page 203: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/203.jpg)
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
![Page 204: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/204.jpg)
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%)
![Page 205: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/205.jpg)
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.
![Page 206: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/206.jpg)
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
![Page 207: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/207.jpg)
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
![Page 208: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/208.jpg)
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
![Page 209: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/209.jpg)
Torisel™(Temsirolimus)
![Page 210: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/210.jpg)
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
![Page 211: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/211.jpg)
Tygacil®(Tigecycline)
![Page 212: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/212.jpg)
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
![Page 213: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/213.jpg)
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%
25%ESBL (K. pneumoniae)
Latin America
MRSA 35%VRE 2%
45%ESBL (K. pneumoniae)
Source: SENTRY Data 2001Definitions: (MRSA) methicillin-resistant staphylococcus aureus, (VRE) vancomycin-resistant enterococcus,(ESBL's) extended spectrum beta lactamases
![Page 214: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/214.jpg)
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
![Page 215: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/215.jpg)
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
![Page 216: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/216.jpg)
Tygacil®(Tigecycline)
Joseph Camardo, M.D.Senior Vice President
Global Medical Affairs and North American Medical Director, Wyeth Pharmaceuticals
![Page 217: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/217.jpg)
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
![Page 218: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/218.jpg)
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
![Page 219: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/219.jpg)
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
![Page 220: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/220.jpg)
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
![Page 221: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/221.jpg)
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
![Page 222: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/222.jpg)
* 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
![Page 223: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/223.jpg)
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
![Page 224: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/224.jpg)
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
![Page 225: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/225.jpg)
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
![Page 226: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/226.jpg)
‡‡Quinolones
‡3rd/4th
Gen Cephs
Tazocin
Carbapenems†
Tygacil
PseudoPseudoAtypicalAtypical
Resistant Resistant Gram Gram
NegativeNegative
Resistant Resistant Gram Gram
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®
![Page 227: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/227.jpg)
‡‡Quinolones
‡3rd/4th
Gen Cephs
Tazocin
Carbapenems†
Tygacil
PseudoPseudoAtypicalAtypical
Resistant Resistant Gram Gram
NegativeNegative
Resistant Resistant Gram Gram
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
![Page 228: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/228.jpg)
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
![Page 229: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/229.jpg)
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
![Page 230: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/230.jpg)
First-in-class, expanded broad spectrumIV antibiotic
Tygacil® Product Profile
![Page 231: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/231.jpg)
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
![Page 232: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/232.jpg)
First-in-class, expanded broad spectrumIV antibiotic
Tygacil® Product Profile
Launched for cIAI, cSSSI
NDA for CAP/HAP and Resistant Pathogens Mid 2007
Status
> $1 BillionPeak Sales
Current indications for cIAI and cSSSI
CAP/HAP/RP indications coming
Monotherapy, empiric treatment for serious, complicated or resistant infections
![Page 233: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/233.jpg)
Bifeprunox
Alliance with Solvay in theUnited States, Canada and Mexico
![Page 234: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/234.jpg)
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
![Page 235: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/235.jpg)
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
![Page 236: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/236.jpg)
Bifeprunox
R. Michael Poole, M.D., F.A.C.P.Vice President, Neuroscience
Therapeutic Area DirectorWyeth Research
![Page 237: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/237.jpg)
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
![Page 238: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/238.jpg)
CATIECATIENIMH trial of outpatient schizophrenia treatment1460 patients treated for 18 months74% of patients discontinued treatment earlyKey insight: individualized treatment is critical
![Page 239: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/239.jpg)
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
![Page 240: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/240.jpg)
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
![Page 241: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/241.jpg)
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
![Page 242: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/242.jpg)
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
![Page 243: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/243.jpg)
“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
![Page 244: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/244.jpg)
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
![Page 245: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/245.jpg)
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
![Page 246: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/246.jpg)
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
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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
![Page 248: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/248.jpg)
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
![Page 249: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/249.jpg)
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
![Page 250: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/250.jpg)
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
![Page 251: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/251.jpg)
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
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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
![Page 253: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/253.jpg)
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
![Page 254: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/254.jpg)
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
![Page 255: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/255.jpg)
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
![Page 256: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/256.jpg)
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
![Page 257: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/257.jpg)
* 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
![Page 258: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/258.jpg)
Methylnaltrexone
Alliance with Progenics
![Page 259: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/259.jpg)
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
![Page 260: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/260.jpg)
OIC is Drug-Induced Dysfunctionof the GI Tract
![Page 261: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/261.jpg)
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
![Page 262: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/262.jpg)
Methylnaltrexone Is Not a Laxative
![Page 263: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/263.jpg)
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
![Page 264: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/264.jpg)
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
![Page 265: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/265.jpg)
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
![Page 266: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/266.jpg)
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
![Page 267: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/267.jpg)
Post Operative Ileus(POI)
![Page 268: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/268.jpg)
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.
![Page 269: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/269.jpg)
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%
![Page 270: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/270.jpg)
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
![Page 271: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/271.jpg)
Methylnaltrexone
Joseph Camardo, M.D.Senior Vice President
Global Medical Affairs and North American Medical Director, Wyeth Pharmaceuticals
![Page 272: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/272.jpg)
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
![Page 273: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/273.jpg)
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
![Page 274: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/274.jpg)
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
![Page 275: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/275.jpg)
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
![Page 276: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/276.jpg)
Methylnaltrexone Subcutaneous Is Well Tolerated
No serious safety events related to the drug
Most common side effects
Abdominal cramping
Flatulence
Nausea
Dizziness
![Page 277: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/277.jpg)
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
![Page 278: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/278.jpg)
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.
Ex-U.S. within1 year
NDA (for AI):Early 2007 in U.S.†
Ex-U.S. within1 year
Patients with chronic pain
Expansion beyond advanced illness (AI)
Phase 2 (Adaptive) (Ongoing)
Phase 3 (Completed)
OralOralSubcutaneousSubcutaneous
† Potential for priority review
![Page 279: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/279.jpg)
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
![Page 280: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/280.jpg)
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
![Page 281: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/281.jpg)
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
![Page 282: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/282.jpg)
R&D: Innovation Continues to Fuel Wyeth’s Long-Term Growth
Robert R. Ruffolo, Jr., Ph.D.Senior Vice President, WyethPresident, Wyeth Research
![Page 283: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/283.jpg)
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
![Page 284: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/284.jpg)
Highlights FromThe Middle of the Pipeline
![Page 285: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/285.jpg)
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
![Page 286: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/286.jpg)
Oncology Strategy
![Page 287: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/287.jpg)
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
![Page 288: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/288.jpg)
Phase 0 Phase 1 Phase 2 Phase 3
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
![Page 289: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/289.jpg)
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
![Page 290: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/290.jpg)
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
![Page 291: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/291.jpg)
= 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
![Page 292: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/292.jpg)
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
![Page 293: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/293.jpg)
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
![Page 294: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/294.jpg)
Signaling Inhibitors Target Critical Growth Pathways in Cancer Cells
EGFEGFEGF
Tumor cell migration, invasion, metastasis
Tumor cell bioenergetics and growth
PI 3-kinasePI 3PI 3--kinasekinase
mTORmTORmTOR
AKTAKTAKT
SrcSrc
Torisel™
Bosutinib (SKI-606)HKI-272
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Signaling Inhibitors Target Critical Growth Pathways in Cancer Cells
EGFEGFEGF
Tumor cell migration, invasion, metastasis
Tumor cell bioenergetics and growth
PI 3-kinasePI 3PI 3--kinasekinase
mTORmTORmTOR
AKTAKTAKT
SrcSrcBosutinib (SKI-606)
![Page 296: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/296.jpg)
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
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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
![Page 298: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/298.jpg)
Signaling Inhibitors Target Critical Growth Pathways in Cancer Cells
EGFEGFEGF
Tumor cell migration, invasion, metastasis
Tumor cell bioenergetics and growth
PI 3-kinasePI 3PI 3--kinasekinase
mTORmTORmTOR
AKTAKTAKT
SrcSrc
HKI-272
![Page 299: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/299.jpg)
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
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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):
Clinical Activity Observed:
Phase 1 Clinical Trial:HKI-272 Preliminary Clinical Activity
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November 2005 March 2006
Pre-treatment 17 Weeks of HKI-272
Phase 1 Study- HKI-272 Preliminary Clinical Activity (Breast Cancer Patient)
![Page 302: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/302.jpg)
Signaling Inhibitors Target Critical Growth Pathways in Cancer Cells
EGFEGFEGF
Tumor cell migration, invasion, metastasis
Tumor cell bioenergetics and growth
PI 3-kinasePI 3PI 3--kinasekinase
mTORmTORmTOR
AKTAKTAKT
SrcSrc
Torisel™
![Page 303: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/303.jpg)
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)
Clinical Activity Observed:
Status:
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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
![Page 305: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/305.jpg)
Alzheimer’s Disease Strategy:“War” On Alzheimer’s Disease
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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
![Page 307: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/307.jpg)
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
![Page 308: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/308.jpg)
Phase 0 Phase 1 Phase 2 Phase 3
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
![Page 309: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/309.jpg)
Phase 0 Phase 1 Phase 2 Phase 3
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
![Page 310: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/310.jpg)
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
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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
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Neuropathology Leading to Cognitive
Dysfunction
AβAmyloid Protein
β-Amyloid Deposits
Beta Secretase Gamma Secretase
Beta Amyloid Peptide
Aβ
Inhibition of the Amyloid Pathway
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Neuropathology Leading to Cognitive
Dysfunction
AβAmyloid Protein
Beta Secretase Gamma Secretase
Beta Amyloid Peptide
Aβ
ACC-001 (Active Immunization)
Clearance from Brain Resulting in Neuroprotection
Inhibition of the Amyloid PathwayTherapeutic Vaccine: Plaque Removal
β-Amyloid Deposits
![Page 314: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/314.jpg)
Neuropathology Leading to Cognitive
Dysfunction
AβAmyloid Protein
Beta Secretase Gamma Secretase
Beta Amyloid Peptide
Aβ
Clearance from Brain Resulting in Neuroprotection
BapineuzumabAAB-002(Passive Immunization)
Inhibition of the Amyloid PathwayPlaque Removal
β-Amyloid Deposits
![Page 315: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/315.jpg)
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
![Page 316: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/316.jpg)
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
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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)
![Page 318: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/318.jpg)
Neuropathology Leading to Cognitive
Dysfunction
AβAmyloid Protein
β-Amyloid Deposits
Beta Secretase Gamma Secretase
Beta Amyloid Peptide
Aβ
PAZ-417(Plasminogen Activator Inhibitor)
Inhibition of the Amyloid PathwayPrevention of Plaque Formation
![Page 319: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/319.jpg)
Neuropathology Leading to Cognitive
Dysfunction
AβAmyloid Protein
β-Amyloid Deposits
Beta Secretase Gamma Secretase
Beta Amyloid Peptide
Aβ
GSI-953 (Gamma Secretase Inhibitor)
Inhibition of the Amyloid PathwayPrevention of Plaque Formation
![Page 320: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/320.jpg)
Neuropathology Leading to Cognitive
Dysfunction
AβAmyloid Protein
β-Amyloid Deposits
Beta Secretase Gamma Secretase
Beta Amyloid Peptide
AβLecozotanSRA-444SAM-315SAM-531SAM-610
Inhibition of the Amyloid PathwayCognitive Improvement
![Page 321: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/321.jpg)
-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
![Page 322: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/322.jpg)
LecozotanSRA-444SAM-315SAM-531SAM-610
Neuropathology Leading to Cognitive
Dysfunction
AβAmyloid Protein
β-Amyloid Deposits
Beta Secretase Gamma Secretase
Beta Amyloid Peptide
AβPAZ-417(Plasminogen Activator Inhibitor)
GSI-953 (Gamma Secretase Inhibitor)
ACC-001(Active Immunization)
BapineuzumabAAB-002(Passive Immunization)
“War” on Alzheimer’s Disease
![Page 323: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/323.jpg)
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
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Examples From Wyeth’sThree Technology Platforms
Vaccines
MnB
Small Molecules
HCV-796
Proteins
TRU-015
![Page 325: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/325.jpg)
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
![Page 326: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/326.jpg)
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
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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)
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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
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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
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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
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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
![Page 332: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/332.jpg)
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
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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
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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
![Page 335: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/335.jpg)
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
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Wyeth R&D Productivity Model
12 Compounds Entering Development
⇓ 70% Success Rate*
8 INDs Submitted
⇓ 40% Success Rate*
3 Compounds Reach Phase 3
⇓ 60% Success Rate*
2 Major NDAs Submitted per Year
Target
* Standard Pharmaceutical Industry Success Rates in 2000
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Revised R&D Productivity ModelInstituted in 1Q06
15 Compounds Entering Development
⇓ 80% Success Rate (was 70%)
12 INDs Submitted
⇓ 25% Success Rate (was 40%)
3 Compounds Reach Phase 3
⇓ 65% Success Rate (was 60%)
2 Major NDAs Submitted per Year
Target
![Page 338: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/338.jpg)
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
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Increase efficiency
Increase quality
Reduce costs
Reduce cycle times
Improve consistency
Increase success rates
Improve decision-making
Changing theClinical Development Paradigm
![Page 340: wyeth 2006 Analysts Meeting Presentation](https://reader033.vdocuments.mx/reader033/viewer/2022051516/554c17f6b4c905ec518b4ebb/html5/thumbnails/340.jpg)
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)
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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
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Shift From a Phased Development to “Learn and Confirm” Paradigm
… to Learn and Confirm
Phase RPhase RLearn Confirm
Transition Zone
IND NDA SubmissionPOC
ConfirmLearn
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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
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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.
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Key Registration Submissions
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Pristiq™ (Depression)
Viviant™ (Osteoporosis Prevention)
Pristiq (Vasomotor Symptoms)
Lybrel™ (Continuous Contraception)
Protonix® Adult Granules
BeneFIX® Reformulation
Compounds Submitted for Registration and Awaiting FDA Approval
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Bifeprunox (Schizophrenia)
Torisel™ (Renal Cell Cancer)
Effexor® (Japan)
Significant Registration Submissionsto Be Filed in 4Q06
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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
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Pristiq™ (Neuropathic Pain)
Pristiq (Fibromyalgia)
Methylnaltrexone Oral(Opioid-Induced Constipation)
Rapamune® (Liver Conversion)
Lybrel™ (Premenstrual Dysphoric Disorder)
Major Regulatory SubmissionsPlanned For 2008
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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
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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
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Conclusion
Bernard PoussotPresident and Vice Chairman, Wyeth
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Wyeth Future Growth Prospects
Growth of In-Line Products
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Incremental Revenue Potential
Enbrel®
Tygacil®
Prevnar®
Greater Than $1 Billion
Growth of In-Line Products
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New Product Opportunities
Wyeth Future Growth Prospects
13v PnC - Adult
Pristiq™
Aprela™/Viviant™
Methylnaltrexone
Greater Than$1 Billion
$500 Million -$1 Billion $250 Million
Torisel™
Bifeprunox
Lybrel™
Growth of In-Line Products
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Wyeth Future Growth Prospects
Growth of In-Line Products
New Product Opportunities
Operational Excellence
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Wyeth Future Growth Prospects
Growth of In-Line Products
New Product Opportunities
Operational Excellence
Improved Manufacturing Efficiencies
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Wyeth Future Growth Prospects
Growth of In-Line Products
New Product Opportunities
Operational Excellence
Improved Manufacturing Efficiencies
Strong R&D
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Wyeth Future Growth Prospects
Growth of In-Line Products
New Product Opportunities
Operational Excellence
Improved Manufacturing Efficiencies
Strong R&D
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Wyeth is positioned to bea stronger company
at the end of the decadeand enter the next decade with
great momentum.
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