wyeth 2006 annual review

Leading the Way to a Healthier World Annual Review 2006

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Page 1: wyeth 2006 Annual Review

Leading the Way to a Healthier World

Annual Review 2006

Page 2: wyeth 2006 Annual Review

Wyeth is one of the world’s largestresearch-based pharmaceutical and healthcare products companies. It is a leader inthe discovery, development, manufacturing and marketing of pharmaceuticals, biotech-nology products, vaccines, non-prescription

medicines and animal health care productsthat improve the quality of life for peopleworldwide. The Company’s major divisionsinclude Wyeth Pharmaceuticals, WyethConsumer Healthcare and Fort DodgeAnimal Health.

Wyeth at a Glance


1 Chairman’s Report to Stockholders

7 Wyeth’s Pipeline for Innovation

8 An Expanding and Promising

Near-Term Pipeline

12 The War on Alzheimer’s

32 Selected Products from Wyeth

33 Directors and Officers

34 Financial Review

36 Corporate Data

IBC Mission, Vision and Values

Financial Highlights

Year Ended December 31, (In thousands except per share amounts) 2006 2005

Net Revenue $20,350,655 $18,755,790

Net Income 4,196,706 3,656,298

Diluted Earnings per Share 3.08 2.70

Dividends per Common Share 1.01 0.94

Total Assets 36,478,715 35,841,126

Stockholders’ Equity 14,652,755 11,994,369

A Special Report on Alzheimer’s Disease

Millions of people around theworld are coming face to face with Alzheimer’s disease, a neurodegenerative disorder thatrobs sufferers of their memories,their identities and, ultimately, their lives. Wyeth is at the forefrontof an extraordinary effort to find new and better medicines to control this disease’s symptomsand, potentially, to halt or evenreverse its progression. A specialreport beginning on page 12 takes an in-depth look at Wyeth’swar on Alzheimer’s.

On the Cover

Motivational life coach MeredithFroemke takes Enbrel for herrheumatoid arthritis. “Within sixweeks of therapy, I felt like a newhuman being,” she marvels. “It’sgiven me back my mobility and mylife.” Her daughter, Lauren, alsohas benefited from an innovativeWyeth medicine after being vaccinated with Prevnar to helpprevent invasive pneumococcal disease. Wyeth is a leader in innovation through use of pharmaceutical, biotech and vaccine technologies.

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I am pleased to report that 2006 was an excellent year for Wyeth. Building on our

strong performance in 2005,we once again delivered on ourcommitment to expand ourgrowth, strengthen our posi-tion for the future and lead the way to a healthier world.Driven by the steady growth of our key products, Wyethreported record revenue. We filed four New Drug Appli-cations (NDA) for new products, demonstrating solidproductivity from our research and development (R&D)efforts. Overall, our new product pipeline significantlyexpanded and advanced. By maximizing productivity,controlling costs and delivering high value, we helped position Wyeth to address the economic realities of achanging health care environment. And, as we have done every year, during 2006 we continued to listen toour stakeholders, to learn from them and to apply thoselessons to our business.

Highlighted below are some of Wyeth’s significantachievements during 2006 and in early 2007. Thesedemonstrate the success of our efforts and our potentialto build upon them:• Wyeth’s 2006 net revenue increased 9 percent to

nearly $20.4 billion, a record high for the Company.Pro forma earnings grew 14 percent, the second consecutive year of double-digit growth. An in-depthreview of our 2006 performance is provided in Wyeth’s 2006 Financial Report, the companion pieceto this Annual Review.

• We achieved annual sales of more than $1 billion foreach of six core product franchises: Effexor, Prevnar,Protonix, Enbrel, Wyeth Nutrition and the Premarinfamily – demonstrating the breadth and diversity of our portfolio.

Robert Essner, Chairman and Chief Executive Officer

• Revenue from all of ourbiotechnology products in2006 reached $5.7 billion,representing about a third of Wyeth Pharmaceuticals’total revenue and makingWyeth the fourth largestbiotechnology company inthe world.

• In January 2007, we received an approvable letterfrom the U.S. Food and Drug Administration (FDA)for Pristiq, a serotonin-norepinephrine reuptakeinhibitor for the treatment of major depressive disor-der, which will be launched with a specific focus on women.

• Wyeth Consumer Healthcare provided an importantrevenue contribution and positioned itself for futuregrowth through the introduction of innovative newproducts such as Advil PM.

• Sales for Fort Dodge Animal Health rose 6 percent,driven by increased revenue from its companion animal and livestock products. The division’s robustnew product pipeline is expected to continue as asource of strong growth.

• We increased our dividend to stockholders for thesecond consecutive year, demonstrating the confi-dence we have in our Company’s future and in thestrength of its financial resources.

In the section that follows this report, you will read about how we’re striving to improve world healthand sustain our growth through a near-term pipeline of innovative products. And in a special feature storyon an area of enormous unmet need – Alzheimer’s disease – you will read about how Wyeth researchersare seeking critical breakthroughs for patients, theircaregivers and society.

Chairman’s Report to Stockholders

“We once again delivered on ourcommitment to expand our

growth, strengthen our position for the future and lead the way

to a healthier world.”

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Wyeth Pharmaceuticals

Our pharmaceutical business deliveredoutstanding results by

extending the reach of ourproducts and enhancing theirpotential for further growth.At the same time, WyethPharmaceuticals took signifi-cant steps to increase the efficiency and responsivenessof its sales organization and to expand a variety of educational efforts for patients.

Effexor and Effexor XR continued as the world’snumber one antidepressant franchise. Sales reached $3.7 billion in 2006, an increase of 8 percent. An additional indication for use of Effexor XR in panicdisorder contributed to growth while the results of the PREVENT study provided further evidence of thesustained efficacy of Effexor XR in treating majordepressive disorder.

Prevnar (Prevenar outside the United States) was the number one selling vaccine in the world, with 42 million doses manufactured and net sales of nearly$2 billion, an increase of 30 percent over 2005. Strongglobal usage of Prevenar accelerated in 2006 as ninemore countries, including Germany, Mexico and the United Kingdom, added Prevenar to their NationalImmunization Programs (NIP). In total, 16 countrieshave incorporated Prevenar into their NIPs, and growing evidence of the vaccine’s high value createsopportunities for further expansion.

Protonix, for erosive acid reflux disease, grew 7 percent to approximately $1.8 billion. During theyear, RENEW, an innovative patient educational program for Protonix, was launched, providing samplestarter medications and educational materials to facilitate discussions between patients and their physi-cians and to help ensure patient compliance over thelonger term.

Worldwide net sales for Enbrel, the number one biotechnology product in its category in NorthAmerica, grew 20 percentto more than $4.4 billion.This includes sales in theUnited States and Canadathat are recorded by our

marketing partner Amgen Inc. While all regions con-tributed to growth, strongest results came from Europe,where sales increased 33 percent, making Enbrelthe number one ranked biotechnology product there.

Wyeth Nutrition is a world leader in the develop-ment, manufacture and distribution of scientificallybased nutritional products for infants and toddlers.Wyeth Nutrition continued to grow at double-digitrates in 2006. Global sales grew to $1.2 billion, anincrease of 15 percent over 2005. The two regionsenjoying the fastest growth were Asia/Pacific, whichcomprised nearly 60 percent of global nutritional salesand grew 23 percent, and Latin America, which madeup 16 percent of global sales and grew 15 percent.

Having recently celebrated its 90th anniversary,Wyeth Nutrition has evolved into a significant interna-tional player with 60 affiliates selling our productsaround the world. The Company markets its premiumproduct line under the Gold banner and, in late 2006,was first to market with an innovative new productcalled Gold with lutein, which seeks to protect the eyesof infants. To meet increasing demand for providinginfants and toddlers with high-value products like theGold line, Wyeth Nutrition increased its manufacturingcapacity in Mexico and began construction of anexpanded facility in the Philippines.

“Our pharmaceutical business delivered outstanding results by

extending the reach of our products and enhancing their potential

for further growth.”

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Wyeth remained a global leader in hormone therapies and was the U.S. market leader as sales of the Premarin family of products increased 16 percent globally and 21 percent in the United States. New datapublished in 2006 helped to further clarify the benefitsand risks of hormone therapy for women, and Wyethcurrently is working with physicians and their patientsto appropriately address patient needs based on theemerging data.

Zosyn (Tazocin outside the United States) contin-ued to be the largest selling I.V. antibiotic worldwidewith global net sales of $972 million, a 9 percentincrease over 2005. The success of Zosyn is attributa-ble to its clinical efficacy and its ability to help hospitals control the emergence of resistant bacteria.Tygacil, our new antibiotic product, also delivered netsales growth during the year. Since its launch in 2005,it has gained 55 worldwide regulatory approvals and now is available in 33 markets. Tygacil is particu-larly important in hospitals for patients infected with common as well as more dangerous resistantinfectious pathogens in complicated skin/skin-structure and intra-abdominal infections.

All these products require the right selling modelfor a changing health care environment. We’re pleasedto report that the new primary care selling model weimplemented in the United States last year is workingwell. In 2006, we jumped from No. 8 to No. 1 in theHealth Strategies Group’s annual primary care physi-cian audit, which demonstrates physicians’ initial satisfaction with our new structure.

Wyeth Consumer Healthcare

Excluding the impact of revenue from Solgar Vitamin and Herb, which was divested in 2005, sales for Wyeth Consumer Healthcare increased

1 percent to more than $2.5 billion in 2006, spurredlargely by a strong focus on supporting our core global brands.

Three growth drivers – Advil, Centrum and Caltrate – benefited significantly from this strategy. The Advil franchise grew 7 percent around the world,largely fueled by new marketing efforts. In Canada,Advil increased its market share and became the leaderin the analgesic category for the first time. The Cen-trum family of vitamin products achieved 4 percentsales growth, driven by innovations in Europe andgrowth in the age 50+ population. Centrum Advantagewas launched in the Canadian market in 2006. Caltrate grew 3 percent largely due to internationalexpansion.

Overall, international sales increased 2 percentwhile U.S. sales declined 3 percent. The decline in the United States primarily resulted from the ongoingimpact of legislative restrictions on sales of pseu-doephedrine-containing cough/cold formulations. Inresponse to these restrictions, Wyeth ConsumerHealthcare transitioned most of its products to analternative active ingredient. This reformulation isexpected to impact sales favorably in 2007. Outsidethe United States, a number of major internationalmarkets enjoyed double-digit growth, includingCanada, China, Colombia, Mexico, Portugal, Taiwan,Thailand and Venezuela.

Wyeth Consumer Healthcare was particularly successful in achieving operating efficiencies to fund new investments and increase net income. Innovationalso was a key contributor to growth, highlighted bythe successful launch of Advil PM. Opportunities for future growth now are being developed, including an innovative Caltrate food-grade line in China, thestart of a consumer health care business in Russia, and an intense research and development effort todeliver new forms of Advil.

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Fort Dodge Animal Health

Sales of our Fort Dodge Animal Health products moved closer to $1 billion, reaching $936 millionand increasing 6 percent over the prior year. In

2006, Fort Dodge received pan-European regulatoryapproval to market ProMeris/ProMeris Duo, productsoffering flea and tick protection for dogs and flea protec-tion for cats. Approval in the United States is expected in the first half of 2007. Another key achievement wasthe U.S. launch of Suvaxyn PCV2 One-Dose, a vaccinefor the prevention of porcine circovirus, a disease thatleads to a wasting syndrome in pigs. In the face of globalconcerns over avian influenza, Fort Dodge receivedapproval for Poulvac Flufend, a new inactivated reversegenetics vaccine for poultry that addresses the potentialpandemic strain of the avian influenza virus.

Research and Development

Our greatest challenge at Wyeth is to create breakthrough medicines that serve the needs of patients in an increasingly competitive envi-

ronment. From a research and development standpoint, that challenge requires thinking and acting differently in discovering and advancing to market potentiallyimportant compounds. That is why we have instituted anew Learn and Confirm paradigm for drug development– a two-phase approach to streamlining the traditionalmultiple phases of development. This effort placesgreater emphasis on high-performing teams, rapid decision making and improved clinical trial designs.Other accomplishments include the creation of a global network of 10 early clinical development centers to optimize our global patient mix, the streamlining of clinical data collection processes using electronic data

capture, and the simplification of clinical trial materialshipments and processes through a strategic alliancewith a leading, worldwide logistics provider.

We continued to realize solid results from our R&D organization, drawing upon our expertise in threedistinct discovery platforms: small molecules, biologicsand vaccines. In 2006, Wyeth filed NDAs for Viviant,for prevention of postmenopausal osteoporosis; Pristiq,for non-hormonal treatment of moderate to severe vasomotor symptoms associated with menopause;Torisel, for patients with advanced renal cell carcinoma,which received priority review status; and bifeprunox –filed with our partner Solvay Pharmaceuticals – for thetreatment of schizophrenia. In addition, we submittedregulatory applications for a reformulation of BeneFIX,one of our hemophilia agents, as well as for a new adultgranule-dose formulation of Protonix, and we receivedregulatory approval for new dosing recommendationsfor Rapamune in high-risk renal transplant patients.Wyeth also is seeking to expand its presence in the con-traceptive market with Lybrel, currently awaiting finalFDA approval. Lybrel is a novel, continuous-use oralcontraceptive that is designed to provide significant benefits in terms of menstrual-cycle regulation.

During the year, we successfully advanced 15 newmolecular entities and two new vaccine constructs from discovery into development. In total, over the past six years, 75 new drug candidates were placed into devel-opment, the majority having potential to be first- or best-in-class therapies. That has made Wyeth a leadingcompany within our industry peer group in discoveringnovel molecules and advancing them rapidly into clinicaldevelopment. We also believe that our pipeline is amongthe most robust in the industry. Others share our positiveviews. For example, early in 2007, R&D Directionsmagazine recognized Wyeth as the company with the bestcentral nervous system product pipeline in the industry.

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In 2007, we expect tosubmit several important filings, including Viviant, forthe treatment of osteoporosis;Aprela, for the treatment of menopausal symptoms andprevention of postmenopausalosteoporosis; methylnaltrex-one subcutaneous, for opioid-induced constipation in advanced medical illness;methylnaltrexone I.V., for post-operative ileus; andTygacil, for use in community-acquired pneumonia andhospital-acquired pneumonia.

A Special Report on Alzheimer’s Disease Research

Ibelieve that Alzheimer’s disease is the biggest health care issue of my generation. More than 4.5 million Americans suffer today, and, as the baby boomer

generation ages, it is expected that this number willgrow substantially. Add to that millions more affectedby the disease – the families and caregivers of Alzheimer’spatients – and the billions of dollars in health care costsborne by society, and the nature of the challenge and the critical importance of doing everything we can toovercome it become clear. Clinical research in this field is complex and expensive with outcomes uncertain, but the impact of success would be enormous.

We’re proud that Wyeth is at the cutting edge in seeking new drugs not only to treat Alzheimer’s diseasesymptoms better than currently available therapies butpotentially to stop or even reverse the course of this crippling and ultimately fatal disease. Our goal is to turnthe corner on this terrible illness and provide new hope.

Success will come notjust in the laboratory but also on the regulatory front and through the development of strong part-nerships with patientgroups, government, regula-tory agencies, and scientistsin industry and academia.

We must encourage additional research, accelerated andinformed new drug reviews, and more aid to caregiverswho bear the brunt of this health scourge. You will readabout some of the patients and their caregivers in thisreport. These family members are courageous beyondmeasure in doing everything in their power to try to carefor their loved ones at home.

The People of Wyeth

Our Company has exhibited a track record of consistency, performance and responsibility. The people of Wyeth know that to continue

on this path, we must maintain a relentless focus on improving our Company and running it even moreefficiently. Our people understand that we have animperative to change Wyeth fundamentally in order to succeed in the years ahead. At its core, this effort isbased on two simple ideas. First, every year we will aim to grow our revenue through the quality of ourproducts and their value to the people we serve. And second, every year we will aim to grow our profit at a faster rate than our revenue by running our Companymore efficiently and productively. These goals drive our results and determine how they are evaluated andhow we plan to improve upon them in the future.

Wyeth’s New Product Pipeline





2001: 49 projects 2006: 77 projects



NME = New molecular entity LCM = Life cycle management



Wyeth Research and Development Expenses($ in billions)









“We continued to realize solid resultsfrom our R&D

organization, drawing upon our expertise in three

distinct discovery platforms …”

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Changes in Management

Iam pleased that we have continued to strengthen the leadership of our organization in a variety of ways. In October 2006, we welcomed Raymond J. McGuire

to our Company’s Board of Directors. Mr. McGuire is a Managing Director and Co-Head, Global InvestmentBanking, for Citigroup Global Markets Inc. I know hewill provide important perspectives on our business oper-ations and strategy. In January 2007, Bernard Poussotwas elected Chief Oper-ating Officer of Wyethand joined the Com-pany’s Board of Direc-tors. Earlier in 2006, hewas promoted to Presi-dent and Vice Chairmanof Wyeth. In his morethan 20 years with ourCompany, Mr. Poussot’sleadership has helped ustransform our organiza-tion and set it on acourse for continualgrowth. Also in 2006,Kenneth J. Martin waspromoted to ChiefFinancial Officer andVice Chairman ofWyeth. In addition toheading our financeorganization, Mr. Martin took on responsibility for ourinfrastructure initiative, which is critical to our operatingefficiency and, therefore, to our future success. Furthersupporting our management team, Joseph M. Mahadywas named President – Global Business for Wyeth Phar-maceuticals and continues as a Senior Vice President ofWyeth. In his new role, Mr. Mahady assumes operationalresponsibility for Wyeth’s global pharmaceutical business.With this expanded responsibility, I am certain he willbring significant insights to our worldwide business andcommercial portfolio. In addition, Geno J. Germano wasnamed President and General Manager, Wyeth Pharma-ceuticals – United States and Wyeth Pharmaceutical Business Unit. Robert E. Landry, Jr., was elected Treasurerof Wyeth.

Corporate Social Responsibility

W yeth recognizes its significant responsibilitiesas a global corporate citizen. One of the mostimportant actions we can take in this regard

is to expand access to our medicines. Our patient assis-tance programs in 2006 provided free Wyeth medicines,

valued at $160 million, to 250,000 Americans who were without adequate prescription drug coverage orinsurance. Outside the United States, we worked to sup-port maternal health care, ensure access to reproductiveand child health resources, and develop a new treatmentoption for river blindness. We are working with theGlobal Alliance for Vaccines and Immunization to findan affordable and sustainable way to bring vaccines tochildren in the developing world. We also are workinghard to help protect and enrich the environment in the communities where we live and work by steadilyreducing environmental emissions and ensuring thesafety of employees at all of our facilities.

Looking to the Future

As we look to the future, we know that we will be operating in a tough environment around the world. To compete, we will continue

to attract, retain and engage a diverse workforce thatbroadens our perspectives, enhances our customer connections and increases our creativity. The more pro-ductive and innovative we are in our operations, the better we will be in addressing concerns about pricingand access to our medicines.

We have made important progress in a relatively shorttime as part of a longer-term effort to find new and moreefficient ways to meet the challenges of the 21st century.The momentum we now have can be accelerated. We will continue to foster a high-performance culture whereevery person has a role, every person takes responsibilityand every person acts to make a difference. We will continue to execute against aggressive plans and developsystems to help ensure both success and compliance withthe highest legal and ethical standards around the world.And we will foster innovation through our creativity,challenging what we do every day and seeking improve-ments and opportunities for the years ahead. Our goal,over the next decade, is to make Wyeth a stronger company with an even higher value portfolio of prod-ucts to fuel growth.

I want to take this opportunity to thank the peopleof Wyeth for making a difference for our Company and those we serve. Thanks to their efforts, our growthhas accelerated, our pipeline never has been stronger andwe are on the path to deliver important new medicinesto a world in great need.

Robert EssnerChairman and Chief Executive OfficerFebruary 26, 2007

Kenneth J. Martin, Chief FinancialOfficer and Vice Chairman, left, and Bernard Poussot, President, ChiefOperating Officer and Vice Chairman.

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Wyeth’s Pipeline for Innovation

Phase 2Determination of safeand effective dosage foran experimental medi-cine, generally conductedin hundreds of patients

Phase 3Determination of overallbenefit/risk ratio for anexperimental medicine,generally conducted inthousands of patients

Regulatory ReviewEvaluation of safety and efficacy data by governmental regulatory agencies

Since 2004, Wyeth has submitted 11 New Drug Applications (NDA) in the United States, delivering on our goal offiling two NDAs for new molecular entities a year. And, over the past six years, 75 new drug candidates were placedinto development, the majority having potential to be first- or best-in-class therapies. This chart presents a snap-shot of new drugs from Wyeth that currently are in human trials or are being reviewed by regulatory agencies.

Women’s Health and BoneLybrel™ (levonorgestrel/EE)Continuous contraceptionPremenstrual dysphoric disorderPristiq™ (desvenlafaxine succinate)Vasomotor symptoms of menopauseViviant™ (bazedoxifene)Postmenopausal osteoporosis prevention Postmenopausal osteoporosis treatmentAprela™ (bazedoxifene/conjugated estrogens)Postmenopausal osteoporosisVasomotor symptoms of menopauseDibotermin alfa (rhBMP-2) injectable Closed fractures

NeuroscienceBifeprunoxSchizophrenia (U.S.)Bipolar disorderEffexor XR® (venlafaxine HCl)Major depressive disorder (Japan)Pristiq™ (desvenlafaxine succinate)Major depressive disorderFibromyalgiaNeuropathic painBapineuzumab (AAB-001)Alzheimer’s diseaseLecozotan (SRA-333)Mild to moderate symptoms of

Alzheimer’s diseaseVabicaserin (SCA-136)Schizophrenia

Gastrointestinal/MetabolicProtonix® (pantoprazole sodium)Adult granules formulationMethylnaltrexone Subcutaneous for opioid-induced

constipation in advanced medical illnessI.V. for post-operative ileusOral for opioid-induced constipationPPM-204 Type 2 diabetes

Vaccines and Infectious Disease13-valent pneumococcal conjugate vaccinePrevention of pneumococcal disease in

infants and children 6 months to 2 yearsPrevention of pneumococcal disease in

high-risk individuals and adults > 50 Tygacil® (tigecycline)Community-acquired pneumoniaHospital-acquired pneumonia Resistant pathogens HCV-796 Hepatitis CMeningococcal B vaccinePrevention of meningococcal disease in


Inflammatory Disease TRU-015Rheumatoid arthritis

Oncology/Immunology/HemophiliaBeneFIX® (coagulation factor IX –

recombinant)Reformulation – hemophilia BMylotarg® (gemtuzumab ozogamicin)Relapsed acute myeloid leukemia (EU)Torisel™ (temsirolimus)Renal cell carcinomaMantle cell lymphomaRapamune® (sirolimus)Conversion in liver transplantReFacto® AF (antihemophilic factor –

recombinant)Hemophilia ABosutinib (SKI-606)Breast cancer, chronic myeloid leukemia,

pancreatic cancer, non-small cell lung cancer

HKI-272Breast cancer, non-small cell lung cancer

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Viviant (bazedoxifene)

Viviant, a selective estrogen receptormodulator, is undergoing regulatoryreview for the prevention of post-menopausal osteoporosis while continuing in Phase 3 clinical trialsfor the treatment of postmenopausalosteoporosis. The National Osteo-porosis Foundation estimates thatapproximately 8 million women inthe United Stateshave osteoporosisand another 22 mil-lion are at risk fordeveloping this disease. Each year,osteoporotic frac-tures cost the coun-try’s health caresystem an estimated$18 billion.

In August 2006,the U.S. Food andDrug Administration(FDA) accepted theViviant New DrugApplication (NDA)for the prevention of osteoporosis. In2007, Wyeth plansto submit an additional NDA forViviant for the treatment of osteo-porosis. If approved, Viviant willrepresent the first new agent in its class in nearly 10 years and will provide physicians with a newoption for patients at risk of osteo-porosis and fracture.

Aprela (bazedoxifene/conjugated estrogens)

During 2007, Wyeth is planning tofile an NDA for Aprela for the treat-ment of vasomotor symptoms andvaginal atrophy and for the preven-tion of osteoporosis, three majorcomplications of menopause. Aprelarepresents the first Tissue SelectiveEstrogen Complex product andseeks to provide the most compre-

hensive therapyfor menopauseas well as a new paradigmfor treatment of osteoporosis.The addition of conjugatedestrogens tobazedoxifenefor the relief ofa wide range of menopausalsymptoms(including hotflushes) isexpected to addsignificant valuefor patients,potentially

making the bazedoxifene family acomprehensive approach to treat-ment of postmenopausal vasomotorsymptoms and postmenopausalosteoporosis.

At Wyeth, manyimportant new

drugs have been filed with regulatoryauthorities or are in late-stage clinical development,encompassing treatmentsthat span a variety of therapeutic areas, includingwomen’s health care, neuroscience, cancer andinfectious disease..

Positioned for Growth: An Expanding and Promising Near-Term Pipeline

Important New Drugs Projected for Filing through 2007

Women’s Health Care

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Pristiq (desvenlafaxine succinate)

Pristiq, a serotonin-norepinephrinereuptake inhibitor, is being developedwith a specific focus on women. The product will have two indica-tions: the treatment of majordepressive disorder and the relief of moderate to severe vasomotorsymptoms associated withmenopause.

Pristiq is expected to improve the balance of serotonin and norepi-nephrine relative to that providedby serotonin reuptake inhibitorsbecause of its pharmacologic profileas a dual reuptake inhibitor. Thisbalance is thought to be importantin depressed women who, whentransitioning through menopause,often experience a fluctuation ordecline in estrogen that may directlyor indirectly diminish both serotoninand norepinephrine functioning.

Pristiq also has been studied for thetreatment of hotflushes associated withmenopause, and marketing applicationsfor this use were filedwith the FDA and theEuropean MedicinesAgency in 2006. Ifapproved, Pristiqwill be the first non-hormonal treatmentindicated for the relief of vasomotorsymptoms.

Additional clinicaltrials now are underway to evaluate the effectivenessand safety of Pristiq as a treatmentfor fibromyalgia syndrome and diabetic neuropathic pain. NDA filings for these two indicationsmay occur as early as 2009.

Lybrel (levonorgestrel/ethinyl estradiol tablets)

Lybrel is an investigational oral contraceptive that contains a well-studied combination of low-dose levonorgestrel and ethinyl

estradiol. If approved, it is expectedto be the only combi-nation oralcontraceptiveindicated forcontinuoususage, 365days a year,without aplacebo phaseor a pill-freeinterval. This product,when takenconsistently, is designed to

make it possible for many women to eliminate the bleeding associatedwith the menstrual cycle while pro-viding effective contraception. In theUnited States, an approvable letterfor Lybrel was received from theFDA in June 2006, and, in the Euro-pean Union, the marketing applica-tion for Lybrel, under the tradename Anya, also is being reviewed.

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Torisel (temsirolimus)

Torisel is a specific inhibitor ofmTOR (mammalian target ofrapamycin), a signaling protein thatregulates cell growth and new bloodvessel formation. U.S. and EU filingsfor Torisel were submitted in Octo-ber 2006. It is undergoing priorityU.S. regulatory review and receivedfast track status for the treatment ofadvanced renal cell carcinoma(RCC). Torisel currently is in clini-cal trials for several other cancers,including mantle cell lymphoma.

RCC accounts for about 85 per-cent of all renal cancers. Patientswith the most advanced form of thedisease have a five-year survival rateof less than 20 percent. Recently,Wyeth reported data showing thatpatients who were treated with tem-sirolimus alone experienced a 49percent increase in median overallsurvival time compared withpatients treated with interferon-alpha alone. In addition to improv-ing overall survival, Toriselpreserved a patient’s quality of life,potentially helping treated patientslive longer and feel better.

Other Oncology Compoundsin Development

Wyeth’s pipeline contains severalinnovative cancer compounds thatare in the middle stages of develop-ment and are expected to advance tolarger clinical trials.

SKI-606 or bosutinib, currently inPhase 2, is a cell signaling inhibitorthat targets critical growth path-ways in cancer cells that allow cellsto divide. Clinical trial data thus farshow activity in imatinib-resistantpatients with chronic myelogenous

leukemia (CML). CML accounts forbetween 15 percent and 20 percentof all adult leukemia cases in West-ern populations.

HKI-272, also in Phase 2, is a cellsignaling inhibitor that focuses oninhibiting tumor cell growth. Thisagent targets a specific growth fac-tor receptor signaling molecule,HER-2, which is found on the sur-face of some breast cancer cells. It isbeing studied in advanced breastcancer patients who have failedstandard therapy. Early clinical data from these very early and very small trials show encouragingpatient responses, including shrink-age of breast and lung tumors.

CMC-544 or inotuzumab, currently in Phase 1, is using a novelapproach called antibody-targetedchemotherapy. Mylotarg, also fromWyeth, uses similar technology and currently is indicated for thetreatment of acute myelogenousleukemia. CMC-544 initially isbeing developed for treatment ofnon-Hodgkin’s lymphoma.


An NDA for bifeprunox for thetreatment of schizophrenia was submitted to the FDA in October2006. Wyeth co-develops and co-promotes bifeprunox in the UnitedStates, Canada and Mexico withSolvay Pharmaceuticals.

The safety data for bifeprunoxconsistently have shown a favorableweight and metabolic profile in both short- and long-term studies.Weight gain is a common and serious side effect of older atypicalantipsychotics and can causepatients to stop taking their medica-tion. While bifeprunox has beenshown to have a smaller mean effectin acute psychosis when comparedwith older atypical antipsychotics, it may be especially useful in stabilized patients who need to be maintained on therapy over the long term because of its favorablemetabolic profile.



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Tygacil (tigecycline)

Tygacil was launched on a globalbasis in 2005 for the treatment of complicated skin and abdominalinfections. Developed as anexpanded, broad-spectrum antibi-otic for patients with acute infec-tions who are admitted to ahospital, it offers a high likelihoodof effective treatment when thepathogen causing an infection isunknown and, more important,when certain resistant pathogens are suspected.

Tygacil also was developed tocombat gram-positive resistant bacteria, including resistant Staphy-lococcus aureus, and gram-negativebacteria, including ESBL-producingKlebsiella pneumoniae. It representsa new weapon in the global battleagainst antibiotic resistance.

Wyeth is targeting an NDA filing for Tygacil in 2007 to include community-acquired pneumonia,hospital-acquired pneumonia andadditional evidence of effectivenessin the treatment of infections causedby certain atypical pathogens. Hospital-acquired pneumonias areof particular importance because of the relatively high rate of morbid-ity and mortality associated withthis condition. In addition, resistantorganisms are becoming moreprevalent in pneumonia, furtherincreasing the risk of mortality.


Opioid analgesics, such as mor-phine, are among the most widelyused medicines to treat patients with moderate to severe pain. However,their use often results in opioid-induced constipation or OIC, a common and serious side effect that can be a barrier to effective painmanagement. The constipation canbe severe enough to require tempo-rary discontinuation of the neededopioids – thus leaving the patientwith inadequate pain relief – or surgical intervention. Every year, an estimated 5 million patients sufferfrom OIC in the United States alone.There currently is no approved medication that specifically targetsthe cause of OIC without interferingwith pain relief.

Methylnaltrexone is a selectiveopioid antagonist being studied as a treatment to block the peripheral side effects of opioid analgesics. The drug is designed to reverse OIC rapidly and consistently withoutreversing analgesic effects or inducing withdrawal symptoms.

Methylnaltrexone is being developed in subcutaneous and oraldosage forms as first-in-class treat-ment platforms for OIC. It also isbeing developed in an intravenous(I.V.) form for post-operative ileus, a potentially serious impairment ofgastrointestinal function that candelay surgical recovery and prolonghospitalization.

Wyeth is developing methylnal-trexone in collaboration with Progenics Pharmaceuticals, Inc. Thecompanies plan to submit NDAs for subcutaneous methylnaltrexonein early 2007, I.V. methylnaltrexonein late 2007 or in early 2008 andoral methylnaltrexone in late 2008or early 2009.

Prevnar 13(13-valent pneumococcal conjugate vaccine)

Since the introduction of Prevnarpneumococcal 7-valent conjugatevaccine in the United States, the Centers for Disease Control and Prevention estimates that invasivepneumococcal disease (IPD)addressed by the Prevnar serotypeshas been reduced 94 percent in children and 55 percent in adults. In addition, the rate of antibiotic-resistant IPD has decreased substan-tially in infants and young childrenand in adults over age 65.

Building on this significantadvance in public health, Wyeth isdeveloping Prevnar 13, a 13-valentpneumococcal conjugate vaccine thattargets 13 strains of S. pneumoniae.This new vaccine currently is under-going worldwide Phase 3 trials inboth children and adults, with regu-latory submissions expected to beginin 2009. If approved, Prevnar 13would be the most complete vaccineavailable for the prevention of pneu-mococcal disease and otitis media inyoung children. For adults, Prevnar13 is expected to extend protection topersons age 50 and older and to pro-vide them with long-term protection.

Infectious DiseaseGastrointestinaland Metabolic Vaccines

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WARon Alzheimer’s

Each morning, for more years than I wish to remember,” says Meryl Comer, a 62-year- old award-winning broadcast journalist,

“I reintroduce myself to my husband, Harvey. I say, ‘Good morning, love. My name is Meryl. I am your wife. We’ve been married for 25 years.Don’t worry. This is your home. And you aresafe.’ His eyes are blank, and mine fill with tears.”Dr. Harvey Gralnick, once a leading researcher at the National Institutes of Health, has hadAlzheimer’s disease for 12 years. Meryl, his caregiver, has been suffering for just as long.

Dr. Gralnick is among 4.5 million Americanswith Alzheimer’s disease. In the United States, itstrikes one of every 10 people over age 65 andnearly half of those over age 85. About 18 millionpeople suffer worldwide – millions more when

caregivers are added to the toll. Treatments costthe U.S. health care system more than $100 billionannually. In the next 20 years, the number of victims will increase sharply, with the potential tobankrupt our health care system. “There are nocures, no remissions,” says former Speaker of the U.S. House of Representatives and Center forHealth Transformation founder Newt Gingrich.“You won’t meet an Alzheimer’s survivor becausethere are none. The need for medical break-throughs never has been greater.”

Wyeth is on the leading edge of potentialbreakthroughs, having declared an all-out war on the disease. This special report introduces the faces of Alzheimer’s, the weapons being developed and the battles that still need to bewaged – and won.


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“Good morning, love. My name is Meryl. I am your wife …”

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Understanding the Enemy

A Primer on Alzheimer’s Disease

One hundred years after Alois

Alzheimer, a German psychiatrist andneuropathologist, firstcharacterized the plaquesand tangles in the autop-sied brain of a victim of this crippling and ulti-mately fatal degenerativedisease, researchers still are not fully certainwhat causes Alzheimer’sor exactly what the rightstrategy is to defeat it.

“Alzheimer’s diseasewas widely misunder-stood for many years,”says Sid Gilman, M.D.,professor and Chair of the Department of Neu-rology at the University ofMichigan and Director ofthe Michigan Alzheimer’sDisease Research Centerthere. “As people aged, it was widely believed that they simply lost theirmemory. Today, somephysicians still thinkmemory loss is normal asyou grow older. That’s not so. You should retainyour memory until youdie. Alzheimer’s is a dis-ease process, and aging isjust one risk factor.”

What may be the primary culprit? Manyresearchers believe it is thetoxic form of a protein –called amyloid precursorprotein – that appearsnaturally in small quanti-ties in our bodies. Whentwo enzymes – gamma secretase and beta

secretase – cut this proteinin certain ways, normalamyloid transforms intobeta-amyloid peptide. It becomes sticky andaggregates together in thebrain. Eventually, theseaggregates accumulatebetween the nerve cells inparts of the brain respon-sible for memory andjudgment.

Samuel Gandy, M.D.,Ph.D., Chair of theNational Medicaland ScientificAdvisory Council of theAlzheimer’sAssociation,notes, “Theamyloid peptide nor-mally is foundbetween nervecells in yourblood or in yourspinal fluid. The chal-lenge is why it becomes

insoluble in some peopleafter six decades of beingfluid. The aggregation, for whatever reason, leadsto a misfolding of the protein. And once it takesshape as what basically is a bobby-pin-like structure,it becomes locked in thatstructure and accumulates,forming amyloid plaques.As that happens, you seethe characteristic lesions of

Alzheimer’s disease.”The other

abnormal pro-tein thatappears in the disease iscalled tau,which accu-mulates inthe cells

themselves,leading to the

tangles that Dr. Alzheimer first

saw. The tangles developinside the nerve cells,eventually killing them.Some drugs are focusing

on ways to inhibit tangles,though many scientistsnow believe that theseform later in the diseaseprocess – perhaps drivenby the amyloid deposition.

Symptoms ofAlzheimer’s diseaseinclude loss of memory –first short term and eventually the ability toremember the past or create new memories; difficulty in speaking andreading; disorientation;and, ultimately, loss ofcapacity to dress, bathe or perform what com-monly are called activities of daily living. Says Dr. Gandy: “Over time,all of the outside surfaceof the brain, all of thecerebral cortex – the partthat’s responsible forthinking – degenerates,and patients die bed-bound in a vegetativestate.”

Joel Ross, M.D., hasbeen a practicing geriatri-cian and internist for thepast 20 years and has seensome 1,000 Alzheimer’spatients during that time.“Anger and depressionare common in early disease. Psychosis is notunusual in later disease.And the wandering wesometimes see is a func-tion of disorientation and lack of memory.”

Left: This CT scan of a brainshows the atrophy caused byAlzheimer’s disease.

This photomicrograph shows the outermost layer of the brain of an Alzheimer’s disease sufferer. The red-colored accumulations arebeta-amyloid plaques.


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“I would do anything to keep him just the way he is today.”

June and Ted Roderick: They’re a Couple

June and Ted Roderick are at the leading edge of thebaby boomer generation – a time when many think

about retirement, new hobbies, vacation plans, grand-children. But June and Ted are too preoccupied for that. Ted, age 63, has Alzheimer’s disease and has had it for at least six years.

“We’re fortunate because Ted continues to function at a high level,” his wife June says. “He’s still drivingand can read short articles in the newspapers and magazines.”

Ted also can take apart a faucet and put it backtogether and make screens for storm windows. He says,“I feel more competent doing mechanical tasks thanmental things. I just forget stuff.” And he speaks ration-ally about his disease. “I can’t remember what I did an hour ago or yesterday. It’s annoying, but, for now, it’s not debilitating.”

Memory problems and confusion at his last job as achemical salesman contributed to his employment beingterminated in April 2005. Ted explains: “I made a lot ofmy sales calls by phone, but I couldn’t remember exactlywhat people had said to me after I hung up. I was takenout of sales and put in other jobs. Was it fair? It’s hard to say.”

Ted finds humor a good defense mechanism. “Actu-ally, it’s a good excuse if I don’t want to do somethingaround the house. I can say, ‘I forgot.’ They’re the two words I use most.” But sometimes it’s hard. “Junewill arrive home and ask what I did during the day. I know I did things, but I don’t know what they were.It’s frustrating.”

June says, “You take every day and appreciate whatyou have. I would do anything to keep him just the way he is today. We’ve been married 40 years. I hope we can continue the way we are.

“We worry about losing each other,” she adds. “That’swhy we keep fighting and trying to do everything we can to prevent the disease from getting worse. We won’tstop. We do everything together. You see, we’re a couple.And we want to stay a couple.”


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Changes in personalityalso can include anxietyand apathy or even suspi-ciousness, agitation ordelusion. With the passingof time, victims may lose their ability to swallowand eat solid foods orbecome incontinent.Often they die from theconsequences of beingbedridden or sustaining a physical injury, like abroken hip. Many don’trecover, in part, becausethey can’t remember theyare sick or had an accidentand can’t understanddirections for therapies to help them get better.

“We believe there is a genetic basis for this disease,” says Dr. Gilman.Having the gene calledApolipoprotein E4 putsone at greatest risk, oftenpredisposing a person todevelop the disease soonerrather than later. “If youlook at the universe ofAlzheimer’s patients,” headds, “50 percent havethe ApoE4 gene.”

Included amongknown physical aspects of the disease is the loss of nerve cells that use theneurotransmitter acetyl-choline, a chemical thatthese cells use to commu-nicate with each other.Nearly all the currentlyapproved medicines targetthis aspect of the disease.However, as Alzheimer’sprogresses and nerve cells become impaired tothe point of degenerating,

Dr. Gandy says,“the medicineswe have todaywear off andaren’t effective.They don’tappreciably slowthe progressionof the diseaseand don’t attack the underlyingpathology.” Most researchersnow believe toxic amyloidand tau beginforming yearsbefore symptomsappear. So evenas researchersbegin to seeknew treatmentsfor Alzheimer’s,they are focusingon how to diag-nose the diseaseat its earliestpossible stages.

The basic principle, Dr. Gandy notes, “is totarget the disease beforepermanent damage to neurons occurs. Part of the reason to target amyloid is that it is felt to accumulate early in the disease cascade. Oncethere is an effective ther-apy that treats early stagesof the disease, the field will try to identify patientsearlier and earlier. Wehope this information willlead to prevention ofAlzheimer’s by identifyingpatients most at risk.”

Dr. Gilman agrees: “It would be ideal to look

at risk factors and treat at least adecade in advanceof cognitive decline.The reason for that length of timeis because MotherNature is verycareful. There is somuch redundancyin the brain thatone has to lose huge numbers ofnerve cells before

symptoms develop.” Standard psychologi-

cal testing, coupled with imaging, is about 80 per-cent to 90 percent accuratein diagnosing the diseaseand staging it – from mildto moderate to severe.Diagnosis also includesruling out other possiblephysical or psychologicalcauses that may be moretreatable, such as severedepression, alcoholism,thyroid malfunction,brain traumas or stroke.Scientists are makingprogress toward develop-ing simpler tests for thedisease by identifying

a series of biomarkers, or proteins, whose pres-ence in the blood or spinalfluid may indicate the disease already is at work.

“I would advocatestarting a therapy whenamyloid is just beginningto be deposited – before significant symptomsoccur,” adds Ronald Black,M.D., Senior Director,Neuroscience ClinicalDevelopment at Wyeth.“That is the promise of prevention. It parallelstreatment of breast cancer: Detect and treat at an early stage.”

Wyeth is participatingin the Alzheimer’s DiseaseNeuroimaging Initiative, a five-year public/privatepartnership that hasbrought together industry,academia and the NationalInstitutes of Health to validate biomarkers anddevelop new neuroimag-ing tools.

How do physicianshelp patients when so fewtherapies are available?Among other things, “We encourage them to participate in our clinicaltrials for their own sakeand for the sake of othersafflicted with this devastat-ing disease,” Dr. Gilmansays. “I tell them whatthey can expect next. I prepare them as best Ican. At least today, wehave great hope for bettertreatments – more thanever before. This is thedawn of a new age.”

William Utermohlen,an American artist living in London, chron-icled the progressionof his Alzheimer’s disease in a series of self-portraits, severalof which are shownhere. The top painting,completed shortly afterhe learned he had thedisease, is followed byothers he created asthe disease pro-gressed and affectedhis abilities and per-ceptions. Today, Mr.Utermohlen resides ina nursing home and no longer paints.

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For the past 15 years, Wyeth’s researchhas been focused

on finding new and bettertreatments for Alzheimer’sdisease. The science hasadvanced, and the diseaseprocess has become betterunderstood. And as animal models have beendeveloped to mimic cer-tain aspects of the diseaseand thus can be used totest new therapies, thiswork has taken on anincreased sense of urgencyas well as possibility.

In 2000, that researcheffort accelerated signifi-cantly when Wyethentered into a partnershipwith Elan Corporation toutilize antibodies to allowthe body to fight the poi-sonous amyloid involvedin the disease process. To date, approximately$450 million has beeninvested by Wyeth inAlzheimer’s research –$125 million in 2006alone. Currently, morethan 350 Wyeth

researchers are workingexclusively on the disease. And about 2,700researchers, or 40 percentof Wyeth’s total R&Dstaff, have been orpresently are involved insome aspect of the Com-pany’s work in this areaof clear and significantunmet medical need.

Menelas Pangalos,Ph.D., is Vice President ofNeuroscience Research at Wyeth. “We’ve morethan doubled ourresources in Alzheimer’sdisease research in thelast four years and havetripled the number ofprograms in discoveryand development,” hesays. “Programs havemoved from ideas in peo-ple’s minds to agents inclinical testing. This has

been a huge effort on all fronts.”

With 23 projects atvarious stages of develop-ment, from early discoveryto late-stage clinical trials,Wyeth is the only majorpharmaceutical companythat uses all availabletechnologyplatforms in its develop-ment efforts.These includesmall mole-cules or tradi-tional drugs,biopharma-ceuticals and vaccines. “Wewant to exploreevery option available tous,” says Wyeth Chair-man and Chief ExecutiveOfficer Robert Essner.

“Wyeth is fully commit-ted to our Alzheimer’sprograms, and we willcontinue to do our part totry to harness scientificadvances to overcomeAlzheimer’s disease andimprove the lives ofpatients and families.”

In addition to devel-oping drugs to controlsymptoms more effec-tively than those currentlyavailable, the Company is expending significant

resources on a number of novel approaches toslow, stop or even reversethe progression of thedisease. Quite simply,says Dr. Pangalos, “Today,we are drawing our line in the sand for thenext generation.”

On that battlefront,delaying the onset ormodifying the course of Alzheimer’s remainsthe quest. The impact ofachieving this goal wouldbe huge. According to TheLewin Group, a premiernational health care con-sulting firm, if therapies

“Programs have moved from ideas in people’s minds to agents in

clinical testing. This has been a huge effort on all fronts.”

Creating Hope

New Therapies from Wyeth Move to the Frontlines

Menelas Pangalos, Ph.D., Vice President of Neuroscience Research at Wyeth.

This series of photos represents how Wyeth is seeking to use specially engineered antibodies deliveredto Alzheimer’s patients to stimulate an immune response that will recognize harmful plaque (in green)and allow immune system cells (in red) to engulf the plaque and then begin to destroy it (far right).

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“My dad gave up on everything – except his music – a long time ago.”

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Gilbert Brown: Until the Music Stops

On Wednesdays, when activities are held at a seniorday care center in Montclair, New Jersey, you

might hear the strains of “Blessed Assurance,” a classicgospel song, being played. Sitting at the piano – even in the fog of Alzheimer’s – is Michael Brown’s father,Gilbert, a retired salesman who turned 80 years old in2006 and has had Alzheimer’s disease for at least sevenyears. He is making music. It’s just about the only thing he can do anymore.

Michael and his wife, Diane, moved his father intotheir home two years ago as the disease steadily pro-gressed. “My dad goes to the senior center five days aweek,” Michael says. “But he doesn’t like to participatein any activities that make him think. If he can get awaywith it, he sits with the group that doesn’t want to doanything. But he still plays the piano – traditional gospeltunes – and some afternoons, he even plays requests. He knows about 60 songs by heart. It’s amazing.”

Michael admits, though, that in every other way, hisfather’s Alzheimer’s disease is dispiriting. “He doesn’tknow what to call common items. If you ask him a ques-tion that requires more than a yes or no, his answers are unintelligible,” Michael says. Fearing the next stagesand trying to cope, both Michael and Diane attend anAlzheimer’s Association-sponsored support group forcaregivers once a month at a local church. “Sometimesyou get tips about how to deal with things. And sometimeswhen you see what others are facing, you realize that your situation isn’t as bad as it could be,” Michael says.

For Michael, what hurts most is sitting across fromhis father. “I wish it weren’t happening, recognizing that the man my dad used to be is gone. The hardestthing is that I’ll never see him laugh or really smile again.He displays agitation, anger – or nothing,” Michaelsays. “Dad used to have a lot of wisdom. When youspoke with him, you usually learned something. Nowhe’s just in the room – that’s all.”

As with so many Alzheimer’s caregivers, life haschanged. “Diane and I had envisioned our lives at this stage to be quite different – taking vacations, beingfreer,” he adds. “But instead, we’re home by 5 p.m.every day to take care of my dad. Our lives are on hold right now. My wife is very supportive, but we’reboth weary.”

Gilbert Brown took piano lessons as a child, and he’s been playing the piano and organ his entire life.When Michael and Diane moved him to their home,they arranged for Gilbert’s electric organ to be shipped.“I never see him happy unless he’s playing the piano or organ,” Michael says. “My dad gave up on every-thing – except his music – a long time ago.”

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to delay the onset ofAlzheimer’s becameavailable in the next fiveyears, estimates are thatby 2015, there would be 1.6 million fewer Ameri-cans with Alzheimer’s, andby 2050, there would be5.3 million fewer sufferersin the United States. At thesame time, Medicare and Medicaid – and, therefore,U.S. taxpayers – wouldsave a half trillion dollarsin health care costs.

Ronald Black, M.D.,of the Neuroscience Clinical Developmentgroup at Wyeth, notes

that because no oneknows for certain whatcauses Alzheimer’s, mul-tiple paths must be takento seek treatments. “Wetry not to be dogmaticabout the cause of thedisease. Instead, we try tobe led by the best science.Today, the best sciencepoints to an important, if not pivotal, role forbeta-amyloid in the pro-gression of Alzheimer’sdisease.” Four of Wyeth’sdrugs currently are in

clinical trials to modifythe disease process, all insome way seeking to haltor reduce the formationof harmful amyloidplaque deposits.

“The dis-covery thatamyloid muta-tions cancause rarefamilial casesof Alzheimer’sdisease led to the develop-ment of ani-mal models,”

Dr. Black adds.“These mutant

genes have been insertedinto mice in such a waythat the mice develop amy-loid plaques in the brainsimilar to those found inAlzheimer’s patients. Thesemice have played a criticalrole in testing potentialtherapies. In fact, one ofthe reasons treatments tar-geting amyloid are moreadvanced than otherapproaches has been theability to test these thera-pies in animal models.”

Vaccines and Biologics in Development

The most novelapproach, and somebelieve the most promis-ing, is immunotherapy –a focus of the Wyeth and Elan alliance. Bothpassive and active immu-nization approaches arebeing developed.

Passive ImmunizationAAB-001 or bap-ineuzumab, which receivedfast track status from theU.S. Food and DrugAdministration (FDA), is Wyeth’s most advanceddisease-modifying therapy.It is a monoclonal anti-body that has been engineered to target toxicbeta-amyloid. Currentlyin Phase 2 clinical trials,the antibody works by binding to amyloid-containing plaques in thebrain. In animal models,this clears the amyloidplaques and appears to neutralize some of the toxic effects of

beta-amyloid on neurons.Once the antibody recognizes and attachesitself to the harmfulplaques, cells in the braincalled microglia, part of the body’s immunesystem, engulf the taggedplaques and dissolvethem. The monoclonalantibodies are deliveredto patients through periodic infusions, muchlike chemotherapy treat-ments. The hope is thatthis will slow the progres-sive loss of nerve cells in the brain, prevent further loss of memoryand preserve day-to-dayfunctional abilities.

Active ImmunizationActive immunizationfocuses on the use of thebody’s own immune sys-tem to clear the brain oftoxic amyloid plaques. In this case, a vaccinecomposed of a fragmentof beta-amyloid isinjected, stimulating animmune response in thebody and producing antibodies that attach toexisting plaques anddestroy them. The firsthuman trial with thispotentially breakthroughdisease modifier, calledAN-1792, was halted in2002 when a small num-ber of patients developeda serious inflammation in the brain.

“… if therapies to delay the onset ofAlzheimer’s became available

in the next five years, estimates are that by 2015, there would be

1.6 million fewer Americans withAlzheimer’s, and by 2050,

there would be 5.3 million fewer sufferers in the United States.”

Ronald Black, M.D., Senior Director,Neuroscience Clinical Development at Wyeth.

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Says Dr. Pangalos,“We went back to the lab to figure out what weneeded to do to reducethe possibility of this sideeffect so that we could re-enter the clinic. Whatwe discovered was thatthe vaccine was stimulat-ing T cells, an immuneresponse that causesinflammation in thebrain. Subsequently, wetook a small fragment of the original peptideused in the AN-1792 tri-als and conjugated it to a carrier protein like theone used in Prevnar,Wyeth’s pneumococcalvaccine. We knew thecarrier protein was safeand thus much less likelyto do the same thing asAN-1792. So we used the technology from ourvaccine business andcombined it with our

discoveries in Alzheimer’s research to enable us tobegin the trials againwith an improved clinicalcandidate.” This improvedclinical option, ACC-001, currently is in Phase1 clinical trials.

The University ofMichigan’s Sid Gilman,M.D., has high hopes for this strategy. “Theimmunological approachis the most promising of those we have seen sofar,” he says, “and activeimmunization would be preferable because weshould start treatmentwell in advance of diseaseonset. We would be able to do this by activelyimmunizing people atrisk. But some elderlypeople don’t produce agood antibody response to immunization on

their own so, in thosecases, passive immuniza-tion may be requiredinstead.”

Small Molecules inthe Clinic

Anti-amyloid DiseaseModifiersGSI-953 is a gamma sec-retase inhibitor that seeksto halt toxic amyloid production by inhibitingone of the two enzymaticscissors important in the production of beta-amyloid protein. It is inPhase 1 trials.

PAZ-417 is a disease-modifying treatment currently in Phase 1 thatseeks to slow the diseaseprocess and the progres-sion of cognitive loss.The compound is a plasminogen activator inhibitor that acts in a

completely different wayon beta-amyloid. It is anovel, first-in-class andfirst-in-therapy approach.

Symptomatic TreatmentsLecozotan (SRA-333) is an oral symptomaticagent with a novel mechanism of action thatmodulates neurotrans-mitter pathways toimprove cognitive dys-function. The robustimprovement of cognitiveperformance in preclini-cal models highlights its potential as a next-generation symptomatictherapy in Alzheimer’sdisease. This first-in-class,first-in-mechanism pro-gram is in Phase 2 trials.

Three additionalserotonin antagonists are in development totreat symptoms of the disease. SAM-531, SAM-315 and SRA-444,all in Phase 1, are orallyactive compounds thatmay enhance memoryand reduce the cognitivedeficits caused byAlzheimer’s. During2007, two other agentshave potential to enterhuman trials. These areSAM-610, another sero-tonin receptor antagonist,and AAB-002, a mono-clonal antibody.

Both disease modi-fiers and symptomaticswill be important in

This photomicrograph of a brain section shows the neurofibrillary tangles (in black) that are characteristicof Alzheimer’s disease. These tangles develop inside nerve cells, eventually killing them.

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treating Alzheimer’s dis-ease. “They will make apowerful combination,”says Steve Jacobsen,Ph.D., Associate Directorof NeuroscienceResearch at Wyeth. “Webelieve that by stoppingthe progression of thedisease, the symptomaticswe’re developing canhave more benefit and a longer duration of action.”

Leaving No StoneUnturned

Other studies in earlierstages of discoveryinclude programs thattarget tau and ApoE4.“Our plan is to take as many shots on goal as possible using com-pounds or programs in multiple areas believedto be involved in theAlzheimer’s diseaseprocess,” Dr. Pangalossays. Wyeth researchersare beginning to look at the possibility ofregenerating brain cellslost in Alzheimer’s disease, building on neu-roregenerative researchnow under way at theCompany to help strokevictims.

“We are leaving nostone unturned. We’relooking at ways to modu-late a range of importanttarget classes, includingion channels, proteasesand kinases,” he adds.

Researchers also areseeking to better under-stand the role of glucosemetabolism, cholesteroland inflammation in the disease process. And these scientists aresearching for improvedmodels of disease to better predict efficacyand safety in humans.

Like so many others,numerous Wyethresearchers themselveshave personally wit-nessed the devastationcaused by Alzheimer’s.Peter Reinhart, Ph.D.,who is Therapeutic Area Head of Wyeth’sNeurodegeneration Discovery Department,saw his grandmother

die of Alzheimer’s last year.And both Drs. Jacobsenand Pangalos lost theirgrandmothers to the disease in recent years.

“We’re not unusual,”Dr. Reinhart says. “In fact,we’re all too common. It isa horrible disease. You areforced to watch someoneyou love fade away. One

day you realizethat the personyou are caringfor is not thereanymore –only his or herappearanceremains simi-lar. In the earlystages, the victims clearlyunderstandwhat is hap-pening to

them, and that can drivethem into depression. It isas terrible as any diseaseyou can imagine. And few understand the toll ittakes on caregivers.”

It’s taken a long time tocome up with potentiallymore effective treat-ments. Genes involved in Alzheimer’s first wereidentified in the mid-to-late 1980s. “It normallywould take between

10 and 20 years from thetime the initial targets are identified until thefirst selective drugs are produced,” Dr. Jacobsensays. Yet, notes Dr. Pangalos, “In a few cases,we have gone from con-cept to clinical trials in as little as three years.Sometimes that has comeabout by looking atadvanced programs inother therapeutic areas at Wyeth and thinkingabout how we mightapply them to the treat-ment of Alzheimer’s disease. By using modelsand insights from otherWyeth research areas, wehave reduced our time-lines by several years.”

All agree that even as advances are made inlaboratories, progressmust be made on the regulatory front, wherethe issues, in some ways,are unprecedented andsignificant. “For exam-ple, in short-term studies in patients,” Dr. Blackexplains, “it may be difficult to distinguish aneffect on disease symp-toms from an effect ondisease progression. We are exploring newways of determining the efficacy of drugs onAlzheimer’s patients,including measurementof amyloid in the brain through imaging. We

“Our plan is to take as many shots on goal as possible using

compounds or programs in multiple areas believed to be involved in

the Alzheimer’s disease process … ”

Peter Reinhart, Ph.D., Therapeutic Area Headof Wyeth’s Neurodegeneration DiscoveryDepartment.

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“At least for now, I think she enjoysa good quality of life.”

Steve Szucs:Appreciating Every Day

It was Violet Szucs’ surprise 80th birthday party, and her family had gathered to celebrate. “Everyone was

happy,” her son Steve recalls, “with jokes all around.But I felt something was odd about my mom. She wasn’ther normal self.”

Soon the changes became more apparent. “She usedto call me every week. Then the calling just stopped.When the holidays came, there was no card, no gift. Itwas the first time that had ever happened,” he says.“Finally, my mom, who always was a regular church-goer, stopped going to services. She said, ‘I just don’t feellike it anymore.’ ”

Six months later, in February 2004, a visit to a geriatri-cian confirmed Steve’s fears – Alzheimer’s disease, in themild to moderate stage. Steve temporarily moved in withhis mom the first year after she was diagnosed. “Sheseemed confused and disorganized, and she couldn’t takecare of the house the way she always had,” he recalls.

In late 2004, Violet was enrolled in a trial for an investigational drug that aims to stop the progression ofthe disease. Since it’s a double-blind study, Steve isn’t sure whether his mom is getting active drug or placebo.But he believes he has seen an improvement. “She’s in ahappier mood than she was two years ago though hershort-term memory seems to be getting shorter. Actually,it’s pretty much nonexistent. Sometimes that’s funny. At other times, it’s trying.”

Today, while she spends much of her time with Steve’ssister, Violet lives on her own and goes to adult day carefive days a week – to interact with people. “That seems tohave made a difference in her attitude. At least for now, I think she enjoys a good quality of life,” Steve says.

But it’s a different life. “She quickly loses interest in television,” Steve observes. “She’ll be laughing one minuteand then lean her head back and be sleeping the next. She has a difficult time focusing. She also doesn’t remem-ber the year she was born. I’ll tell her it was 1923, but 10 minutes later, she can’t remember it. She’s not what sheused to be at all.

“Still,” he says, “right now, I’m happy for her. She’senjoying every day as much as she can. And my daughterwill know her grandmother. I know it won’t always be like this so I appreciate the time we have together.”

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“We don’t expect our parents to go through this. They are the people who used to make sure the world was okay for us…”

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Ana Alvarado: Taking Care of Mom

Ana Alvarado is 48 years old. She has her work – as a Spanish teacher – and she has her mom –

Antonia, age 77, who suffers from Alzheimer’s disease.“My mom lives with my brother and me,” Ana says.“Taking care of her is a 24/7 task. I have to get up at 4 a.m. to go to work so I have a homemaker come to our house in the mornings. Later, an aide stays with my mom until my brother gets home from work.”Ana’s sister lives up the street, and, in between jobs,she stops in to make sure everything is okay.

Antonia was diagnosed three years ago afterexhibiting sudden changes in behavior. “You wouldtalk with her, and she’d always make excuses for not doing something. That was very unlike her,” Anareports. “And when our family would get together,she’d get upset because other people were around, andshe felt she wasn’t getting enough attention.”

Today, even as some of those symptoms have abated,Antonia’s memory loss has advanced. “She knows I’ma familiar face, but now and then she’ll ask, ‘Where’sAna?’ She’ll talk about events and people from her earliest years, but she doesn’t remember my father, who died 15 years ago, and she doesn’t know what dayit is,” Ana says. “I’ve seen her get worse. The moodswings vary from day to day.” And other behaviorshave emerged. “When we go out in public, she wantsto physically embrace people in the stores, and shethinks everyone understands Spanish,” Ana notes.“Mom used to speak English but doesn’t anymore, and she watches soap operas but doesn’t know what’s going on.”

Dealing with this has been painful. “I was angry at the beginning, having a mother but not having a mother,” Ana says. “I had to deal with the fact that I no longer could rely on her as a parent.”

Then there are the hardships of caregiving. “At theextreme, I suppose she could go into a nursing home,”Ana adds. “But I don’t want her to do that. I’m Spanish, and we care for our elders. To keep my sanity,I turn a lot of my attention to work.”

Antonia once had another life. “My mom alwayswas a pleasant woman. She was a seamstress and wasvery independent. And she took care of the world,”Ana says. “She was well-dressed, and her makeup wasjust right. But today, even bathing her is a challenge.

“We don’t expect our parents to go through this.They are the people who used to make sure the worldwas okay for us,” Ana adds. “But she’s my child now –and sometimes not an easy child.”

Page 28: wyeth 2006 Annual Review


still will examine mem-ory and quality of lifewhen we evaluate ourdisease-modifying thera-pies, but we hope thesenew endpoints will helpus get our drugs topatients sooner. If theseimages show us that ourdrugs are reducing theamount of amyloid in thebrain or are slowing theloss of neurons, it will be important evidencethat our drugs are imped-ing the progression of the disease. Will every-one, including regulators,agree that these areproper endpoints?” Thediscussions continue.

As more effectivetherapies enter clinicaltrials, Dr. Black believesthat attitudes willchange. “We should be thinking about Alzheimer’s as a disease

where we can make sig-nificant change in theoutcome, along the linesof the improvements wesaw in cancer and HIV inthe last decade. If we canshow that a drug truly isslowing the progressionof a terminal illness, thena higher level of risk maybe acceptable. We haveheard from patients andcaregivers over and over again that they know

Alzheimer’s is a deathsentence,” says Dr. Black.“Similar to cancer patientsand their families, theywant effective therapiesto combat the disease andare willing to accept therisks that may go alongwith these medications.The Alzheimer’s patientsand their families whoparticipate in our clinicaltrials are our biggestallies in this effort.”

Susan Kundel, VicePresident for Neuro-science New Business atWyeth, says, “This is a universally dreaded disease. And now wehave within our grasp thepossibility of doing some-thing about it. We are onthe leading edge of sci-ence, and that meansthere are many uncertain-ties and unknowns. Weexpect to see failures, butwe also anticipate thatwithin a relatively shortperiod of time, we willhave a clear ability tomodify the course of thisdisease. The price forworking in this disease isuncertainty. But whatyou get in return is a lotof hope.”

“We expect to see failures, butwe also anticipate that

within a relatively short period of time, we will have a

clear ability to modify the course of this disease.”

In Alzheimer's disease, the cerebral cortex of the brain, shown in this PET scan, is atrophied due to thedeath of many neurons, and metabolic activity (shown in red) is decreased, leading to cognitive andbehavioral dysfunction.

Steve Jacobsen, Ph.D.,Associate Director of Neuroscience Research at Wyeth.

Page 29: wyeth 2006 Annual Review


Baby boomers fear Alzheimer’s disease and the

shadow it already is casting on the lives ofpeople as they age – andon the lives of those who care for them.

A survey conducted byACT-AD (Accelerate Cure/Treatments for Alzheimer’sDisease), a recently formedcoalition of close to 50leading advocacy groups,asked more than 1,000Americans born between1946 and 1964 about thedisease.

Unprepared for aHealth Care Crisis

Less than 10 percentthink current treatmentsfor the disease are ade-quate. Nearly all say theywould be unprepared orwould find life not worthliving if they were forcedto face the limitationscommon to the disease.And about 80 percent saytheir current savingswould not cover the costof care. Overwhelmingly,they express concernabout the government’sability or even willing-ness to address this looming personal andpublic health care crisis.

Wyeth and othergroups are making a con-certed effort to helpaddress those fears and tochange the landscape oftreatment and care.

ACT-AD representspatients, caregivers, con-sumers, older Americans,researchers and women’shealth advocates. It wasorganized in April 2006and received initial support through an edu-cational grant fromWyeth and Elan Corpora-tion. “Many boomers currently are focused onother health issues andmistakenly considerAlzheimer’s a problem oftheir elders,” says DanielPerry, Executive Directorof the Alliance for AgingResearch and Chair of ACT-AD. “But whenasked to consider them-selves at age 70 with

Alzheimer’s disease, therewas a visceral reactionand an awakening to thereality of what couldawait them.”

Wyeth believes thatpatients, industry andgovernment must partnerto help accelerate researchfor therapies that halt orreverse the progression ofAlzheimer’s disease.

The Need for aGreater Focus onAlzheimer’s

Wyeth Chairman andCEO Robert Essneremphasizes the need to actnow – on many fronts –to better mobilize society’swar on Alzheimer’s.“We’ve all known some-

one – a spouse, a parent,an aunt, an uncle – whohas fallen prey to this disease,” he told a 2005White House Conferenceon Aging. “A recentGallup poll found thatnearly 50 percent of thoseresponding worry aboutdeveloping Alzheimer’sdisease. However, insteadof spurring people intoaction, this knowledgeseems to engender a sense of resignation, ofinevitability. What we lackis a worldwide clamor forimmediate action and asolution. I know of no dis-ease in our country wheremore patients are waitingwith so much need and so little hope. It does nothave to be so.”

Today, in addition to its wide-rangingresearch and developmentefforts to find better and more effective treat-ments, Wyeth is hard atwork partnering withpatient groups, talkingwith regulators in both the United States and interna-tionally, and, in essence,leaving no stone unturnedacross many complex and difficult battlefronts.

“Our aim is to foster a sense of nationalurgency about Alzheimer’sdisease,” says Jill Arent,Senior Director, FederalHealth Policy in Wyeth’sPublic Policy group.“Thesuccessful mechanismsthat the U.S. Food and

“Our aim is to foster a sense of national urgency

about Alzheimer’s disease.”

The Path Forward

Forging Partnerships for Progress

Page 30: wyeth 2006 Annual Review


Drug Administration(FDA) already has developed to address theurgent need for newAIDS and cancer thera-pies can and should be applied to innovativetreatments forAlzheimer’s disease.”

Speaking at a forum,“Preparing the Country forthe Alzheimer’s Epidemic,”Newt Gingrich, Center forHealth Transformationfounder, agreed: “We needto develop a road mapthat would lay out acomprehensive approachto dealing with the societal costs of this dev-astating illness. I hopethis will lead to a con-gressional hearing andconcerted measures bythe legislative and execu-tive branches. Legislatorsneed to be mobilized for Alzheimer’s the way they have been for AIDS and avian flu.”

Outlining a Plan for the Future

A former Speaker of the U.S. House of Repre-sentatives, Mr. Gingrichdescribed specific elements for the path forward: maximizing the evolution of imagingcapabilities for inexpen-sive and routine earlydiagnosis; designing basic

and applied researchtracks to outline thebiggest breakthroughsstill required and deter-mining ways to resourcetheir development; creating an FDA modelof operations for thebrain sciences that cutsacross existing systems to address the realities ofan emerging science; anddeveloping optimumpublic policies to supportcaregivers.

Sid Gilman, M.D., of the University ofMichigan, wants a freshlook at the risk/benefitratio. “We need to viewAlzheimer’s disease as equivalent to cancer. We need to streamline thereview process for med-ication approval as wedid for cancer therapies,meaning we need toaccept higher levels ofrisk. Our medical systemshave not acknowledgedas yet the full impact ofthis disease – its severity,its consequences, itscosts, its horrors.”

A Disease of Two Victims: Patient and Caregiver

Ultimately, Joel Ross,M.D., a practicing geriatrician, recognizeswhat those involved in the disease know too well.Caregiving at home stillcomprises more than 70 percent of allAlzheimer’s disease care.“It is a disease of two victims: the patient andthe caregiver,” he says.“One dies from or withthe disease, and one ispermanently damaged –forever scarred by it. For years at a time, homecaregivers work hard to cope and deal withAlzheimer’s, yet they tryto remain hopeful andoptimistic. Right now, thegovernment pays little or nothing for at-home orday care for sufferers but pays heavily for insti-tutional care. If the government helped homecaregivers pay for theneeded services, thennursing home admissions might be avoided or atleast delayed, saving thegovernment billions of

dollars.” Currently, 50 percent of nursinghome admissions are due to Alzheimer’s disease orrelated disorders.

Demonstrating the Power of the Human Spirit

The Alzheimer’s Founda-tion of America (AFA) isone of the foundinggroups of ACT-AD andrepresents numerousorganizations around thecountry that focus onserving and advocatingfor patients and theircaregivers. “What is aweinspiring is the length andbreadth to which a care-giver will go – in the nameof love – to provide for aspouse, parent or otherrelative. It says somethingabout the human spirit,”says Eric J. Hall, ChiefExecutive Officer of AFA.“What can we do to helpthe increasing number of caregivers and theirloved ones with dementia? AFA has hundreds oforganizations across the country that supportcaregivers and individualswith dementia who nolonger can speak for them-selves. AFA gives them aunited voice, and it givesthem hope. The caregiversand sufferers desperatelyneed champions.”

“We need to develop a road map that would lay out a comprehensive approach

to dealing with the societal costs of this devastating illness.”

Page 31: wyeth 2006 Annual Review

“…there are no magic bullets. Butjust give up? I wouldn’t do that.”

Dick Cone: Bringing Dignity to a Disease

Dick Cone finds strength through his faith. It has helped him remain resolute in his determination to

keep his wife, Phyllis, at home with him as long as he can. “A nursing home for my wife? That’s not goingto happen if I can help it,” he says emphatically.

Phyllis is 77 years old – his age. They’ve been married56 years and live in St. Louis, Missouri. It was clearsomething was wrong with her about 10 years ago. “I first noticed it when she failed to remember a majorconstruction project we had undertaken,” Dick recalls.“When we talked about it, all she could say was, ‘What project?’ ” A definitive Alzheimer’s diagnosiscame in 2002.

Dick’s perseverance led to finding medications that“helped push the clock back about two years or so for her,” he notes, as she found herself unable to partici-pate in activities she once had enjoyed – music, churchgroups, cultural organizations.

But now he sees considerable memory loss. They have two children, but she can’t remember their names.“Sometimes, however, she still calls me Dick. It’s beenawhile since she could read. And she requires assistancewith all the functions of daily living,” he says. WhenDick leaves the house to do volunteer work or to runerrands, someone comes in to help. He’s also spent agreat deal of time remodeling their house to accommo-date Phyllis’ needs. “Since I like to cook, I expanded the kitchen so she can be right there with me.” Headmits it’s tough, though. “There’s not a lot of supportwith Alzheimer’s,” he adds. “And there are no magicbullets. But just give up? I wouldn’t do that.

“I know I’ve lost a lot of her,” Dick continues. “Thephysical relationship is gone. The memories we used to share are gone. While she can’t have a conversation, I know she’s aware – she responds, she still is here withme.” He often invites family and close friends to visit.“Phyllis enjoys being here at home, at the table sur-rounded by others,” he says. “She’s part of the picture.It’s a comfort being in this house. This is the windowthrough which we view the world. This is our yard.These are our flowers. There is a quality of life here.There is family here. My prayer is to help me be strongenough to keep on going … for her.”


Page 32: wyeth 2006 Annual Review


The power of thisdisease and thechallenge of con-

quering it drives us on,”Wyeth Chairman andCEO Robert Essner hassaid. “What we need is asense of urgency analo-gous to that which arosearound AIDS. In the waragainst AIDS, govern-ment, regulatory agencies,scientists in industry andacademia, and patientgroups worked hand inhand to develop new therapies and to evaluatethem as rapidly as possi-ble. The results wereremarkable.”

In addition to its wide-ranging researchand development effortsto find better and moreeffective treatments,Wyeth is hard at workpartnering with patientgroups and talking withregulators in both theUnited States and interna-tionally. The Company isleaving no stone unturnedacross many battlefronts.

Breakthroughs willrequire the best that science can offer as morepotential advances thanever appear in the lab or on the horizon. It willrequire society taking afresh look in the mirror –as we age and as our parents age – to deter-mine the right road map

for the future and howbest to get new drugs andmore hope to patientssooner.

Meryl Comer, picturedon page 13 of this report,believes that Alzheimer’sdisease “should be thebaby boomer’s worstnightmare.” It certainlyhas been for her and her husband, Dr. HarveyGralnick, who has suf-fered with the disease for more than a decade.Meryl gave up a successfulcareer in broadcast jour-nalism in Washington,D.C., to devote herself to his 24-hour care –

sometimes with help butmore often alone – and to be on the frontlines asan advocate for otherpatients and caregivers.

Meryl is upset abouthow Alzheimer’s is seenby others. “Alzheimer’stoo often is portrayed as a benign disease of aging.But my husband main-tained his mind and his body all his life. He hadmore than 200 researchpapers published, he was fluent in three languages, he filled in

answers to crossword puzzles in ink and he was a long-distance runner. But all those activities didn’t make a difference.”

She adds, “I sawwhat happened to myhusband during a briefinstitutional stay, and itmade me physically ill. SoI elected to do whateverwas necessary to keepHarvey from having toleave home for his care.We still may go bankruptafter all these years ofmedical expenses, but Iwill have no regrets.”

John Dwyer is a Washington, D.C., attorney, health careentrepreneur andAlzheimer’s disease advo-cate. “We need to reshapethe debate and dialoguearound Alzheimer’s,” he says. “People need tounderstand the neurologi-cal holocaust thatAlzheimer’s disease repre-sents for society. But, at the same time, we can’tafford a long slog for new treatments. If wewant to give hope to people, the short answer is that we need to developa strategic national planagainst Alzheimer’s disease, and we need toenergize and mobilize the 50- and 60-year-olds who are at risk – and that may be all of us.”

What the Future Holds

Where do we hope to be 10 years from now?

“We need to reshape the debate and dialogue around Alzheimer’s.

People need to understand the neurological holocaust

that Alzheimer’s disease represents for society.”

Page 33: wyeth 2006 Annual Review


“I try to offer as much support as I can, to tell my stories and toshare my experiences.”

Billings Fuess, Jr.: Saying Goodbye

Over the past 10 years, as his wife, Doris, deterioratedfrom Alzheimer’s disease, Billings Fuess, Jr., suffered

alongside her, learning more about loss than he everthought possible. “You lose the one you love bit by bit,”the New Jersey resident and retired advertising copy-writer recalls. “She was slowly sinking below the water’ssurface, and I couldn’t pull her up.

“In the mid-1990s, I began to suspect something waswrong with her mind,” Billings adds. “Over time, Doriscouldn’t read from one line to the next and couldn’t focuson anything. She would get frustrated when watchingmovies because she couldn’t understand all the twists andturns. And she had trouble reading mystery stories formuch the same reason. But she never forgot who I was.”

He believes that after a hip operation two years agoand a stay in the hospital and rehabilitation facility,

Doris’ dementia seemed to accelerate. “She didn’t realizeshe had broken her hip and didn’t know enough to try toget better physically so I could take her home,” he says.“It was bad. She kept falling because she didn’t know shecouldn’t walk.”

But through this self-described nightmare, Billings continued to care for her. “I had my own business, but Ifinally had to dissolve that.” He also started going to a support group. “I found the sessions helpful. It’s toughto deal with this alone. There’s so much heartbreak.”Wanting to help others, Billings still attends the group. “I try to offer as much support as I can, to tell my storiesand to share my experiences.”

On January 7, 2006, Billings and his wife exchangedwedding bands in the rehabilitation facility. “We weremarried in 1952, but we didn’t have a double ring cere-mony back then,” he says. “On that special day last year, we slipped on our rings and it was all very happy.” Thenext day, with her family at her side, she passed away.

“When Doris was well,” he says, “our grandchildrenwere her great joy. She also worked in the bridal registryof a department store and liked to read, visit friends and go antiquing. She touched a lot of people along theway. I miss her dreadfully.”

Page 34: wyeth 2006 Annual Review


Cardiovascular and


Inderal LAProtonixProtonix I.V.Zoton





and Oncology


Infectious Disease


Inflammatory Disease



Effexor/EfexorEffexor XR


NursoyProgressProgress GoldPromilPromil GoldPromisePromise GoldS-26S-26 Gold



Women’s Health Care

Alesse/LoetteLo/OvralMinessePremarinPremarin Vaginal CreamPremphasePrempro/PremelleTotelleTriphasil/Trinordiol

* Co-promoted with Amgen Inc.

The above products are identified as trademarks used by Wyeth and its subsidiaries.

Wyeth Pharmaceuticals

Bronchi-ShieldBursineCYDECTINDuramuneFel-O-Vax/PentofelFluvac Innovator/DuvaxynLymeVaxNolvasanPolyflexPoulvacProHeart/GuardianProMerisPyramidQuest/EquestRabvacSuvaxynSynovexTelazolToDAYToMORROWTorbugesic/TorbutrolTriangleWest Nile-Innovator

Fort Dodge Animal Health

Selected Products from Wyeth


AdvilAdvil PMAnadinChildren’s AdvilRobaxinSpalt


Advil Cold & SinusAlavertChildren’s Advil ColdDimetappRobitussin

Nutritional Supplements

CaltrateCentrumCentrum SelectCentrum SilverPolaseVitasprint B12

Other Products

AnbesolChapStickFiberConPreparation HPrimatene

Wyeth ConsumerHealthcare

Page 35: wyeth 2006 Annual Review


Directors and Officers

Robert Essner 1

Chairman and Chief Executive Officer

John D. Feerick 2,5

Professor of Law, Fordham UniversitySchool of Law

Frances D. Fergusson,Ph.D. 4,5,6

President EmeritusVassar College

Victor F. Ganzi 2,3,12

President and Chief Executive Officer, The Hearst Corporation

Robert Langer, Sc.D. 4,5,6

Institute Professor, Massachusetts Institute of Technology

John P. Mascotte 1,2,3,5,12

Retired President and Chief Executive Officer,Blue Cross and Blue Shieldof Kansas City, Inc.

Raymond J. McGuireManaging Director, Co-Head, Global InvestmentBanking, Citigroup GlobalMarkets Inc.

Mary Lake Polan,M.D., Ph.D., M.P.H. 4,5,6

Professor and ChairmanEmeritus, Department ofObstetrics and Gynecology,Stanford University Schoolof Medicine

Bernard PoussotPresident, Chief OperatingOfficer and Vice Chairman

Gary L. Rogers 2,3

Former Vice Chairman,General Electric Company

Ivan G. Seidenberg 1,3,4

Chairman and ChiefExecutive Officer, VerizonCommunications Inc.

Walter V. Shipley 3,5

Retired Chairman ofthe Board, The ChaseManhattan Corporation

John R. Torell III 2,4

PartnerCore Capital Group

Robert Essner 7,8,9,10,11

Chairman and Chief Executive Officer

Bernard Poussot 7,8,9,10,11

President, Chief OperatingOfficer and Vice Chairman

Kenneth J. Martin 7,8,9,10,11

Chief Financial Officer andVice Chairman

Thomas Hofstaetter,Ph.D. 7,9

Senior Vice President –Corporate BusinessDevelopment

René R. Lewin 7,8,9,10,11

Senior Vice President –Human Resources

Joseph M. Mahady 7,8,9,10

Senior Vice President

Marily H. Rhudy 7,9

Senior Vice President –Public Affairs

Robert R. Ruffolo, Jr., Ph.D. 7,8,9,10

Senior Vice President

Lawrence V. Stein 7,8,9,10,11

Senior Vice President andGeneral Counsel

Ulf Wiinberg 7,9

Senior Vice President

Mary Katherine Wold 10,11

Senior Vice President –Tax and Treasury

Douglas A. Dworkin 8

Vice President and Deputy General Counsel

Leo C. JardotVice President –Government Relations

Paul J. Jones 8,9

Vice President and Controller

Jeffrey E. KeislingVice President – CorporateInformation Services andChief Information Officer

John C. KellyVice President –Finance Operations

Eileen M. Lach 8

Vice President, CorporateSecretary and AssociateGeneral Counsel

David A. Manspeizer 8

Vice President – IntellectualProperty and AssociateGeneral Counsel

James J. PohlmanVice President – CorporateStrategic Initiatives

Steven A. Tasher 8

Vice President –Environmental Affairs andFacilities Operations andAssociate General Counsel

Justin R. VictoriaVice President –Investor Relations

Robert E. Landry, Jr. 11


Fort Dodge AnimalHealthE. Thomas Corcoran 7,9,10


Wyeth ConsumerHealthcare Douglas A. Rogers 7,8,9,10


Wyeth ConsumerHealthcare – InternationalEtienne N. Attar 9


Wyeth Pharmaceuticals –Global BusinessJoseph M. Mahady 7,8,9,10


Wyeth Pharmaceuticals –Asia/Pacific and NutritionalsMark M. Larsen 9


Wyeth Pharmaceuticals –EMEA/CanadaUlf Wiinberg 7,9


Wyeth Pharmaceuticals –Latin AmericaEduardo G. Nieto 9


Wyeth Pharmaceuticals –Technical Operationsand Product SupplyCharles A. Portwood 7,8


Wyeth Pharmaceuticals –United States andWyeth PharmaceuticalBusiness UnitGeno J. Germano 9

President and GeneralManager

Wyeth ResearchRobert R. Ruffolo, Jr.,Ph.D. 7,8,9,10


Principal Division and Subsidiary Officers

Principal Corporate OfficersBoard of Directors

1 Executive Committee2 Audit Committee3 Compensation and Benefits

Committee4 Corporate Issues Committee5 Nominating and Governance

Committee6 Science and Technology Committee7 Management Committee

8 Law/Regulatory Review Committee

9 Operations Committee10 Human Resources and

Benefits Committee11 Retirement Committee12 Designated to be a “Financial

Expert” as defined in applicable SEC rules

Page 36: wyeth 2006 Annual Review


Year Ended December 31, 2006 2005 2004 2003

Net revenue $20,350,655 $18,755,790 $17,358,028 $15,850,632 Research and development expenses 3,109,060 2,749,390 2,460,610 2,093,533 Net income 4,196,706 3,656,298 1,233,997 2,051,192 Diluted earnings per share 3.08 2.70 0.91 1.54 Dividends per common share 1.01 0.9400 0.9200 0.9200 Capital expenditures 1,289,784 1,081,291 1,255,275 1,908,661 Total assets $36,478,715 $35,841,126 $33,629,704 $31,031,922 Number of common stockholders 47,314 50,648 54,301 59,181 Number of employees at year end 50,060 49,732 51,401 52,385 Wages and salaries $ 3,488,510 $ 3,434,476 $ 3,280,328 $ 3,003,555

Selected Financial Data

(Dollar amounts in thousands except per share amounts)

Company Data by Reportable Segment

(In millions)

Year Ended December 31, 2006 2005 2004 2003

Net Revenue from CustomersPharmaceuticals $16,884.2 $15,321.1 $13,964.1 $12,622.7 Consumer Healthcare 2,530.2 2,553.9 2,557.4 2,434.5Animal Health 936.3 880.8 836.5 793.4Consolidated total $20,350.7 $18,755.8 $17,358.0 $15,850.6

Income (Loss) before Income TaxesPharmaceuticals $ 5,186.4 $ 4,544.9 $ 4,040.1 $ 3,798.5Consumer Healthcare 516.2 574.3 578.6 592.4 Animal Health 163.7 139.4 134.8 127.4 Corporate (436.4) (478.0) (4,883.3) (2,156.7) Consolidated total $ 5,429.9 $ 4,780.6 $ (129.8) $ 2,361.6

Depreciation and Amortization ExpensePharmaceuticals $ 719.9 $ 682.0 $ 529.5 $ 458.0 Consumer Healthcare 20.0 40.8 45.7 34.9Animal Health 32.7 30.3 29.9 25.9Corporate 30.4 33.8 17.3 19.1Consolidated total $ 803.0 $ 786.9 $ 622.4 $ 537.9

Expenditures for Long-Lived AssetsPharmaceuticals $ 1,228.3 $ 1,077.9 $ 1,226.5 $ 1,742.1Consumer Healthcare 35.3 28.4 33.2 53.8Animal Health 37.2 45.0 40.0 28.4Corporate 72.0 47.1 83.4 126.3Consolidated total $ 1,372.8 $ 1,198.4 $ 1,383.1 $ 1,950.6

Total Assets at December 31,Pharmaceuticals $ 17,171.6 $15,770.2 $15,771.2 $14,513.7Consumer Healthcare 1,492.9 1,463.2 1,701.4 1,742.8Animal Health 1,430.0 1,326.7 1,340.9 1,328.4Corporate 16,384.2 17,281.0 14,816.2 13,447.0Consolidated total $36,478.7 $35,841.1 $33,629.7 $31,031.9

Page 37: wyeth 2006 Annual Review


2006 2005 2004 2003

PharmaceuticalsEffexor $ 3,722.1 $ 3,458.8 $ 3,347.4 $ 2,711.7 Prevnar 1,961.3 1,508.3 1,053.6 945.6 Protonix 1,795.0 1,684.9 1,590.6 1,493.3Enbrel 1,499.6 1,083.7 680.0 298.9 Nutrition 1,200.8 1,040.9 943.3 857.6 Premarin family 1,050.9 908.9 880.2 1,275.3 Zosyn/Tazocin 972.0 891.6 760.3 638.7 Oral contraceptives 454.9 525.3 590.1 589.2 BeneFIX 357.6 343.3 301.5 248.1 Rapamune 336.9 300.2 259.0 169.8 rhBMP-2 308.0 236.3 165.3 58.1 ReFacto 305.6 268.4 249.4 224.2Zoton 130.8 375.7 447.7 363.2Tygacil 71.5 10.0 — — Alliance revenue 1,339.2 1,146.5 789.9 654.4 Other 1,378.0 1,537.7 1,708.3 1,872.0 Total Pharmaceuticals $16,884.2 $15,321.1 $13,964.1 $12,622.7

Consumer HealthcareCentrum $ 657.1 $ 634.0 $ 616.6 $ 545.6 Advil 620.2 514.0 490.4 450.9 Robitussin 225.5 253.2 237.9 230.3 Caltrate 195.1 189.2 179.0 153.4 ChapStick 127.9 134.4 123.2 113.9 Preparation H 103.1 104.8 102.3 92.3 Dimetapp 81.7 80.4 87.8 85.2 Alavert 49.8 49.5 56.0 81.6 Advil Cold & Sinus 61.0 122.4 129.7 134.7 Solgar — 58.5 105.5 105.1 Other 408.8 413.5 429.0 441.5 Total Consumer Healthcare $ 2,530.2 $ 2,553.9 $ 2,557.4 $ 2,434.5

Animal HealthLivestock products $ 405.5 $ 377.2 $ 351.0 $ 329.2 Companion animal products 283.9 257.8 252.6 226.7 Equine products 135.5 138.2 138.2 147.2 Poultry products 111.4 107.6 94.7 90.3 Total Animal Health $ 936.3 $ 880.8 $ 836.5 $ 793.4

Worldwide Net Revenue by Product

(In millions)

Page 38: wyeth 2006 Annual Review


Corporate Data

Executive OfficesWyethFive Giralda FarmsMadison, NJ 07940(973) 660-5000


Stock Trading InformationWyeth stock is listed on the New YorkStock Exchange (ticker symbol: WYE).

Independent Registered PublicAccounting FirmPricewaterhouseCoopers LLP400 Campus DriveFlorham Park, NJ 07932

Annual MeetingThe Annual Meeting of Stockholderswill be held on Thursday, April 26, 2007at the Hyatt Morristown in Morristown,New Jersey.

Stockholder Account InformationThe Bank of New York is the transferagent, registrar, dividend disbursingagent and dividend reinvestment agentfor the Company. Stockholders of recordwith questions about lost certificates,lost or missing dividend checks, ornotification of change of address shouldcontact:The Bank of New YorkP.O. Box 11002Church Street StationNew York, NY 10286

(800) 565-2067 (Inside the United States and Canada)

(212) 815-3700 (Outside the United States and Canada)

For the hearing impaired: (888) 269-5221 (TDD)

E-mail: [email protected] address: www.stockbny.com

BuyDIRECT Stock Purchase andSale PlanThe BuyDIRECT plan provides stock-holders of record and new investors witha convenient way to make cash pur-chases of the Company’s common stockand to automatically reinvest dividends.Inquiries should be directed to The Bankof New York.

Reports AvailableA copy of the Company’s 2006 AnnualReport on Form 10-K may be obtainedby any stockholder without chargethrough The Bank of New York. Addi-tionally, this report and all Company filings with the Securities and ExchangeCommission can be accessed on our Web site at www.wyeth.com.

Equal Employment OpportunityOur established affirmative action andequal employment programs demon-strate our long-standing commitment toprovide job and promotional opportu-nities for all qualified persons regardlessof age, color, disability, national origin,race, religion, sex, sexual orientation,status as a Vietnam-era veteran or aspecial disabled veteran, or any militaryuniformed services obligation.

Environment, Health and SafetyInformation on the Company’s environmental, health and safety (EHS) performance and its EHS Policy is available on the Web at http://www.wyeth.com/aboutwyeth/citizenship/ehs. EHS information also is included in Corporate Citizenship 2006 – Living Our Values, which is available on the Web at http://www.wyeth.com/aboutwyeth/citizenship. The EHS Policy also may be obtained upon written request to:WyethDepartment of Environment, Health and SafetyFive Giralda FarmsMadison, NJ 07940

Corporate CitizenshipCorporate Citizenship 2006 – LivingOur Values, a report describing theCompany’s efforts in the areas of governance, employee development, support for our communities, and protection of the environment and thehealth and safety of our employees, is available on the Web athttp://www.wyeth.com/aboutwyeth/citizenship or via written request to:WyethPublic AffairsFive Giralda FarmsMadison, NJ 07940

TrademarksProduct designations appearing in differentiated type are trademarks.Trademarks for products that have notreceived final regulatory approval aresubject to change.

Cautionary StatementThe information in this Annual Review isa summary and does not provide com-plete information; it should be consideredalong with the information contained inthe Company’s 2006 Financial Report,2006 Annual Report on Form 10-K andother periodic filings with the Securitiesand Exchange Commission.

This Annual Review includes for-ward-looking statements reflecting the Company’s current views at the timethese statements were made with respectto future events and financial perfor-mance. All forward-looking statementsaddress matters involving numerousassumptions, risks and uncertainties,which may cause actual results to differmaterially from those expressed orimplied by the Company in those state-ments. In particular, the Companyencourages the reader to review the risksand uncertainties described under theheading “Item 1A. RISK FACTORS” in the Company’s 2006 Annual Reporton Form 10-K. Accordingly, the Com-pany cautions the reader not to placeundue reliance on these forward-lookingstatements, which speak only as of thedate on which they were made.






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We bring to the world pharmaceutical and health care products that improve lives and deliver outstanding value to our customers and shareholders.


Our vision is to lead the way to a healthierworld. By carrying out this vision at every level of our organization, we will berecognized by our employees, customers and shareholders as the best pharmaceuticalcompany in the world, resulting in value for all.

We will achieve this by:

• Leading the world in innovationthrough pharmaceutical, biotech andvaccine technologies

• Making trust, quality, integrity andexcellence hallmarks of the way we do business

• Attracting, developing and motivatingour people

• Continually growing and improving our business

• Demonstrating efficiency in how we use resources and make decisions

To achieve our mission and realize our vision, we must live by our values:


We are committed to excellence – in the results we achieve and in how we achieve them.


We do what is right for our customers, our communities, our shareholders and ourselves.

Respect for People

We promote a diverse culture and acommitment to mutually respect our employees, our customers and our communities.


We value people at every level who leadby example, take pride in what they doand inspire others.

Collaboration – “Teamwork”

We value teamwork – working together to achieve common goals is thefoundation of our success.

Mission & Vision Values

Page 40: wyeth 2006 Annual Review

Five Giralda Farms

Madison, NJ 07940