新藥項(xiàng)目引進(jìn)評估方法(Pharma-Business-Development-A-scientist-view)課件

Our

PatientsOur

PeopleOur

BusinessOur

CommunityPharmaceutical

Business

Development

A

Scientist’s

View

Robert

J.

Cobuzzi

Jr.,

Ph.D.

Vice

President

and

Acting

Head,

Corporate

Development

Endo

Pharmaceuticals

Inc.

Non-ConfidentialOurPatientsOurPeopleOurBusi12Non-ConfidentialCobuzzi-UPenn–2December2008DisclaimerThestatementsandviewspresentedaremyownandnotthose

ofmyemployer,EndoPharmaceuticalsInc.

-Bob

Cobuzzi2Non-ConfidentialCobuzzi-UPe23Non-ConfidentialCobuzzi-UPenn–2December2008Presentation

Agenda?Endo

Pharmaceuticals?Pharmaceutical

Business/Corporate

Development?The

Drug

Development

Process:

Integral

to

Business

Development?Licensing

Case

Study

–

GSK-Xenoport?Acquisition

Case

Study

–

AstraZeneca-Medimmune?Any

Questions?3Non-ConfidentialCobuzzi-UPe34Non-ConfidentialCobuzzi-UPenn–2December20084Non-ConfidentialCobuzzi-UPe45Non-ConfidentialCobuzzi-UPenn–2December2008Our

CommunityOur

BusinessOur

PeopleEndo

PharmaceuticalsA

proven

leader

in

pain

management?Specialtypharmaceuticalcompany

withexpertise

in

pain

management?Results-focusedorganizationfueledbyemployees’shared

valuesandacommitmenttomaking

a

differencefor…Our

Patients5Non-ConfidentialCobuzzi-UPe56Non-ConfidentialCobuzzi-UPenn–2December2008Nearly

90

Years

of

History?????1920-Foundedasfamily-runpharmaceuticalbusinessinNewYorkCity-LaternamedEndoProducts1969-DuPontacquiresEndo1997-DuPontMerckExecutivesformEndoinmanagementbuyout-AllofEndoLaboratoriesLLC'sgenericproductspurchased-Dealincluded12keybrandproducts,includingPercocet?andPercodan?!NewcompanynamedEndoPharmaceuticalsInc.2000-EndobeginstotradepubliclyonNASDAQ(ENDP)2007-Netsales$1B+-Compoundannualgrowthrateof20%+since20026Non-ConfidentialCobuzzi-UPe67Non-ConfidentialCobuzzi-UPenn–2December2008A

Successful

Foundation…Building

for

the

Future?????GrowingUS-basedpharmaceuticalcompanySuccessfulsalesandmarketingofbrandedandgenericprescriptionpharmaceuticalsApproximately,500homeofficeemployeesand1,000salesrepresentativesEstablisheddevelopmentcapabilitiesStrongcashpositionwithapproximately$1billion

Build

for

the

Future.

Learn

from

the

Past.7Non-ConfidentialCobuzzi-UPe78Non-ConfidentialCobuzzi-UPenn–2December2008Product

Portfolio8Non-ConfidentialCobuzzi-UPe89Non-ConfidentialCobuzzi-UPenn–2December2008Endo’s

Growth

Strategy

?Movefrombestproducttobest

solution

?Leveragepainadjacencies

?Investinnewtherapeuticareaswith

focusoninnovation

?Concentrateonareasofsignificant

unmetmedicalneed,lowcostof

entry,andspecializedtherapeutics

?Exploreallplatformsincludingsmall

molecule,largemoleculeanddrug-

deviceinterplay9Non-ConfidentialCobuzzi-UPe910Non-ConfidentialCobuzzi-UPenn–2December2008Pharmaceutical

Business/

Corporate

Development10Non-ConfidentialCobuzzi-UP1011Non-ConfidentialCobuzzi-UPenn–2December2008The

deal

is

a

beginning,

not

an

end!???Thepurposeofadealistosolveaproblem

–Peoplemakedealstoaccessgoodsorservices

–OrganizationsmakedealsforthesamereasonEndo’s‘problem’

–Nointernaldrugdiscovery

–Developmentcandidatesandapproveddrugs

sourcedexternallybyBusiness/Corporate

DevelopmentDeal‘solutions’cantakemultipleforms

–Licenses,Acquisitions,Partnerships

–Each‘requires’additionalworkbylicensee

?e.g.,development,marketingand/orsales11Non-ConfidentialCobuzzi-UP1112Non-ConfidentialCobuzzi-UPenn–2December2008License

or

Partnership?License=grantofpermissionto‘use’fromoneentitytoanother–––Molecule,patent,diagnostictest,deviceorotherassetDevelopment,commercializationLimitationsforuses,durationand/orterritory?Partnership=associationoftwoormoreentitiesinwhichtheprofitsandlossesaresharedproportionally–Discovery,development,commercialization?TypicalDealTerms––––Upfrontpayment-upondealsigningDevelopmentand/orcommercializationmilestonesRoyaltyonsalesMonetaryamountsvaryconsiderably?Benefits––PaymentscanbemadecontingentonsuccessDealscanbeterminatedwithsomeconsideration(moneyandnotification)?Risks––CanbemoreexpensivethanacquisitionCounterpartyissues–e.g.,territorycontrol12Non-ConfidentialCobuzzi-UP1213Non-ConfidentialCobuzzi-UPenn–2December2008Acquisition??Typicallypurchaseofanassetorstock

–Asset=organization,product,molecule,patent,diagnostictest,deviceorother

–Stock=publicorprivatecompanyTypicalDealTerms

–Paymentdiffers

–Publicvs.privateentity,development-stagevs.marketedproducts?Stockpurchase

?Assetpurchase–Contingentrightsarepossible–Monetaryamountsvaryconsiderably??Benefits

–Fullownershipandrightstoproductsandcandidates

–Mechanismtoacquireenablingtechnologyorknow-howRisks

–It’syours,period13Non-ConfidentialCobuzzi-UP1314Non-ConfidentialCobuzzi-UPenn–2December2008Evaluating

the

Asset/Entity???Doestheassetaddressacommercial/unmetmedicalneed?

–Toaddressacompletelyunmetneedisrare(e.g.,cureforcongestiveheart

failure)

–Isitsufficientlydifferentiatedfromotheravailabletherapies?Doestheproductbenefitoutweightheriskprofileintheintendedindication?

–Dotheavailabledatasupporteffectiveness?

–Dotheavailabledatasupportacceptablesafetyandtolerability?

–Vioxx?(rofecoxib)andAvandia?(rosiglitazonemaleate)caseshaveraisedthe

bar–arethereany“earlywarningsignals”?Doesthenewproducthavemarketexclusivitythatprovidessufficienttimetorecouptheinvestment?

–Patentlife=20yearsfromfiling–compositionofmatter>use>formulation

–Hatch-Waxmanexclusivity-patentrestoration,particularlyhelpfulifnopatent

?7yearsfororphandrug

?5yearsfornewchemical/molecularentity(NCE/NME)

?3yearsforreformulation14Non-ConfidentialCobuzzi-UP1415Non-ConfidentialCobuzzi-UPenn–2December2008Clear

Strategies

Achieve

Alignment,

Efficiencyand

EffectivenessWhat

a

strategy

tells

the

BD&Lorganization:!Whichassets/technologiesareof

interest!Whatwearewillingtopay!Whenweneedthem(portfolioview)!Wherewearelikelytofindcertain

assets!Whointheorganizationwillchampion

andownthenewlyacquiredassetsHow

you

know

your

strategy

is

clear:!BDcommercialleadersarticulatesame

in-licensingpriorities!FrontlineBDpersonnelhavesufficient

clarityonneedstoscreenout~80%of

dealswithinaday!FrontlineBDpersonnelknowhowto

prioritizeandspendtheirtime!BDorganizationknowswhatmessages

tocommunicatetotheprospective

collaboratorsregardingbusinessneeds15Non-ConfidentialCobuzzi-UP15networkBusiness

Development

ProcessProcess

steps

Identification

Initialscreening

Go/

NoGo

Evaluation

Go/

NoGo

DueDiligence

Go/

NoGo

Negotiation/

Integration

16

Activities!Sourcenewassetsfrom

multiplechannels

!Assessassetagainstpreset

criteria

!Decidewhichassetspassto

nextstep

!Prioritizeassets

!Assessassetagainstpreset

criteria!Decideandprioritizewhich

assetspasstonextstep(or

shouldbeaccelerated).!Developpreliminarybusiness

planwithdetailedevaluation!IdentifyAssetChampion!Decideandprioritizewhich

assetspasstonextstep.!Completenegotiations,deal

structuringandbusinessplan!Integrateassetintoportfolio

Non-Confidential

KOLsPharmaVCAcademia

Biotech

Tech.

I.P.

NCE

505(b)(2)

Cobuzzi-UPenn–2December2008networkBusinessDevelopmentPr1617Non-ConfidentialCobuzzi-UPenn–2December2008

The

Drug

Development

Process:Integral

to

Business

Development17Non-ConfidentialCobuzzi-UP1718Non-ConfidentialCobuzzi-UPenn–2December2008Bob’s

Scientific

“Insights”?????Datatalks…

–Allquestionshaveanswers,thetrickistoaskthe“right”questions

–Goodexperimentshaveonlyoneprimaryendpoint/variableStatisticsonlyidentifytendenciesinpopulations

–Notwoentitiesinapopulationareevenclosetoidentical

–Tendenciesareinformaboutsubgroups/strataMulticellularorganismsaregovernedbyinteractivesystems

–NothinghappensinisolationDeterminationofBenefitvs.Riskistheprimaryobjective

–Contextiseverything

–Non-humanexperimentsprovideinformation,notanswersDrugdevelopmentislearnedthroughexperience,notaclassroom

–Itisnecessarytounderstanddrugdevelopmenttoevaluateadrug18Non-ConfidentialCobuzzi-UP1819Non-ConfidentialCobuzzi-UPenn–2December2008Pharmaceutical

Drug

Development??????Objective=Demonstratethatbenefit(s)>risksIdentifyarelevanttargetandapotentialmodulatorEstablishpreliminarysafety,pharmacologyandchemicalcharacterizationEvaluatehumanpharmacokineticsandpharmacodynamicsStepsmustoccurinaregulatedsequenceintendedtoensuresafety(animalandhuman)aswellasdatareproducibility

–DevelopmentisgovernedbyUSCodeofFederalRegulations(CFR)

Section312andcomparableinternationallawsAlloftheaboveappliestoassetevaluation19Non-ConfidentialCobuzzi-UP1920Non-ConfidentialCobuzzi-UPenn–2December2008Drug

Discovery

(months

to

years)???Identifyaspecificbiologicaltargetcrucialtoaspecificdiseaseprocess

–E.g.,cellsurfacereceptor,ionchannelorenzymeSynthesizeandscreencompounds(tenstomillions)basedupontargetinteraction

–generate“l(fā)eadcompounds”

–Requirement=sufficientpatentprotectiontowarrantdevelopmentcostChoosecompoundsfordevelopmentbaseduponthefollowingcriteria(notcomprehensive):–––––Targetspecificity(i.e.,doesn’tinteractwithothercriticaltargetswithinthebody)SufficientpotencyNoovertorlimitingtoxicity(-ies)ADMEpropertiessupportdesiredeffect(route-dependent)Minimaldruginteractionpredicted?Conductinitialanimalpharmacologystudiestoevaluateactivityinmodelsintendedtomimicthehumanconditionofinterest

–Choosemodelsandinterpretdatacarefully!20Non-ConfidentialCobuzzi-UP20Non-ConfidentialPreclinical

Testing

(9

months

to

3

years)????Animaltoxicologystudiesandfurtherpharmacologiccharacterization

–ExposuredurationinexcessofinitialclinicalexposurePharmacokinetictesting

–FocusedonADME(absorption,distribution,metabolismandexcretion)Physicochemicalcharacterization

–chemicalstructure,purity,stabilityandshelf-lifeChemistry,ManufacturingandControls(aka,CMC)

–Pharmaceuticaldevelopmentstudiestoconverttheactive

pharmaceuticalingredient(API)intotheintendedclinical“doseform”

(e.g.,tablet)

–Optimizemanufacturing(APIandfinaldosageform)onanindustrial

scaleforthelowestfeasiblecost

–Establishstabilityofintendedclinicaldosageform

21Cobuzzi-UPenn–2December2008Non-ConfidentialPreclinicalTe2122Non-ConfidentialCobuzzi-UPenn–2December2008Investigational

New

Drug

(IND)

Application????INDApplication

–SubmittedtotheU.S.FoodandDrugAdministration(FDA)torequestpermission

tobeginhuman/clinicaltesting

–Summarizesresultsofpre-clinicalexperiments

–FDAhas30daystocommentfromtimeofsubmissionApplicationincludesaclinicaltrialplan

–Describesthediseasestate(s)andtypesofhumanstudiesInitialclinicalstudyprotocolisincludedintheIND

–Typicallydescribesmethodologyandanalyticstoidentifyasafeandtolerable

dose

–IndividualstudyprotocolsareapprovedbytheInstitutionalReviewBoard(IRB)ProgressreportsaresubmittedatleastannuallytoFDA22Non-ConfidentialCobuzzi-UP2223Non-ConfidentialCobuzzi-UPenn–2December2008Clinical

Trials

($$$

+

ttt)???Phase1(6monthsto1year)

–Smallpharmacokineticstudiestypicallyin“normalhealthyvolunteers”

–Purpose=identifysafedosagerangeandinitialhumanADMEcharacterization

–Studycosts=$0.5Mto$2MPhase2(6monthsto2years)

–Initialexploratorytrialsinsmallgroupsofvolunteerpatients(n=20to50)to

establishproof-of-conceptintargetdiseasestate(aka,Phase2a)

–Larger,placebo-controlledtrials(n=50-500)withvolunteerpatientstodetermine

optimalefficaciousdose,safetyandtolerability

–Eachstudycosts=$1Mto$50MPhase3(1year–5years)

–Placebo-controlledtrialsthatcanincludethousandsofvolunteerpatientswiththe

diseaseofinterest

–Studiesconfirm(clinicallyandstatistically)drugsafety,tolerabilityand

effectiveness

–Requiresreplicatestudiesatintendeddose

–Eachstudycosts=$1Mto$250M)23Non-ConfidentialCobuzzi-UP2324Non-ConfidentialCobuzzi-UPenn–2December2008New

Drug

Application

(NDA)

Process?NDA=requesttotheFDAforpermissiontomarketthedrug–––AlldatatodemonstratesafeandefficaciousintreatingtheintendedpatientsandcanbemadeconsistentlyDocumentformatandcontentgovernedbyUSCFR314andcomparableinternationallawsTypically!100,000‘pages’ofinformation–filedelectronically?FDA

Review/Approval

(10

to

18

months

)––ReviewtimelinesandsubmissioncostgovernedbyPrescriptionDrugUserFeeAct(PDUFA)FDAcanconveneoutsideAdvisoryCommitteetoaddressspecificissues(e.g.,commentingonaspecificsafetyissuesuchasPML/Tysabri)?NotallNDAsareapprovedoninitialsubmission*––––Only64%ofNDAreviewscompletedin2007resultedinan“Approval”28%ofreviewsweredeemed“Approvable”,8%were“Non-approvable”UnapprovedNDAsnowissued“CompleteResponseLetters”byFDACompleteresponseindicatesindicatesthatchangesmustbemadebeforetheapplicationcanbeapproved,butdoesnotgiveinsightintoultimateapprovability*Source=Reuters2008-/article/pressRelease/idUS130687+09-Jan-

2008+PNW2008010924Non-ConfidentialCobuzzi-UP2425Non-ConfidentialCobuzzi-UPenn–2December2008Post-marketing

Studies???FDArequirescontinuedmonitoringofapprovedproducts

–Spontaneousadverseeventsmustbereportedperiodicallyoronan

expeditedtime-scaledependingonmultiplefactorsFDAmayrequire,orsponsormaychoose,toconductpost-approvalstudies(Phase4)

–Learnmoreaboutthedrugeffectonaparticulargroupofpatients

–SupportariskminimizationprogramStudiesconductedtosupportnewusesofanapproveddrug(newindications)aresubmittedtotheFDAforreviewintheformofaSupplementalNDA

–AnsNDAtypicallyrequireslesstimethantheoriginalNDAtoreview(6-

12months)25Non-ConfidentialCobuzzi-UP2526Non-ConfidentialCobuzzi-UPenn–2December2008

Licensing

Case

Study

‘Beauty

is

in

the

eye

…’GSKLicensesGabapentinProdrugfromXenoport

totreatRestlessLegSyndrome(RLS)26Non-ConfidentialCobuzzi-UP2627Non-ConfidentialCobuzzi-UPenn–2December2008GSK-Xenoport

Joint

Press

Release

LONDON&SANTACLARA,Calif.,Feb08,2007

(BUSINESSWIRE)

GlaxoSmithKline(GSK)andXenoPort,Inc.

(Nasdaq:XNPT)todayannouncedanexclusive

agreementtoco-developandcommercialize

XP13512,auniqueprodrugofgabapentinthat

improvesitsbioavailability,intheUSandother

countriesworldwide,excludingcertainAsian

countries.XP13512iscurrentlyinPhaseIII

developmentforRestlessLegsSyndrome(RLS)

andinPhaseIIdevelopmentforneuropathicpain.

Priorclinicaltrialresultshavebeenencouraging.27Non-ConfidentialCobuzzi-UP2728Non-ConfidentialCobuzzi-UPenn–2December2008GSK-Xenoport

Deal

Terms

?Up-front=$75million

?Aggregatemilestonepaymentsof

–"$65millionfordevelopmentactivitiesleading

uptotheNDAfilingforRLS

–"$210millioninotherpotentialdevelopmentand

regulatorymilestonepayments

–"$290millioninpotentialsalesmilestone

paymentsforRLSandneuropathicpain

–Double-digitroyaltypaymentsonUSsales

unlessXenoPortelectstoco-promote,thennet

profitshare,andentitledtodetailREQUIP

productscurrentlyindevelopmentbyGSK

–AsianrightspreviouslylicensedbyXenoPortto

AstellasPharmaInc.28Non-ConfidentialCobuzzi-UP2829Non-ConfidentialCobuzzi-UPenn–2December2008What

would

you

have

done?

?Whatwasthecommercial/unmetmedicalneed?

?Doestheproductbenefitoutweightheriskprofileinthe

intendedindication?

?DoesthenewproducthaveIPorjustHatch-Waxman

exclusivity–i.e.,istheresufficienttimetorecoupthe

investment?29Non-ConfidentialCobuzzi-UP2930Non-ConfidentialCobuzzi-UPenn–2December2008Restless

Leg

Syndrome

?Causeofpainfullegsthatismorenoticeableatrest

–Symptomsworseninearlyeveningandnight

?Pathobiologypoorlyunderstood

–Comorbidtomultipleconditionsincludinganemia,kidney

disease,diabetes,Parkinson’sdisease,peripheralneuropathy,

migraine,etc.

–Drugsideeffectseenwithantiemetics,anticonvulsants,

antipsychotics,etc.

–Mayrelatetoimbalanceofcentraldopaminergicpathways,

e.g.,hypoactivationofD2receptors30Non-ConfidentialCobuzzi-UP3031Non-ConfidentialCobuzzi-UPenn–2December2008XP13512

(aka,

Solzira?)???Transportedpro-drugofgabapentin

–Intendedtoaddresslowbioavailabilityofgabapentinbytargetinghigh-

capacitynutrienttransporter

–Gabapentinabsorptionislow,saturableandlimitedtoduodenumand

upperjejunum

–Rapidlyconvertedand>70%bioavailableQualifiesasaNewMolecularEntity

–PotentiallylongpatentlifeinadditiontoHatch-WaxmanexclusivityClinicalstudiescomplete,NDAfiled

–Phase3RCTinn=220ptswithmoderatetosevereRLS

?StatisticallysignificantmeanchangefromBLatweek-12inIRLSscale

?SignificantchangeinresponderrateofClinicalGlobalImpressionat12-

weeks

–10Nov2008pressreleaseindicatesNDAwithdrawnbyGSK

?Citedthatdataforasinglestudymustbereformatted

?Delayspaymentof$23MmilestonetoXenoport31Non-ConfidentialCobuzzi-UP3132Non-ConfidentialCobuzzi-UPenn–2December2008Problem

Solved??GSK’sExistingRLSDrugwasRequip?(ropiniroleHCl)

–Non-ergolinedopamineD2andD3dopaminereceptor

agonist

–ApprovedfortreatmentofRLSin2005

–GSKdevelopedtheRLSindicationandmarket??PotentialissueswithRequipforRLS

–Riskofcardiacvalulopathyandotheradverseeffects

–Impendingpatentexpiryofimmediatereleaseform

–Off-labeluseofgabapentinindicatedeffectivenessin

RLSPotentialbenefitsofSolzira

–Neurontinwasahugecommercialsuccesswithalotof

potentialuses,includingRLS

–Longpatentlife

–Relativelybenignsafetyprofileofgabapentin(sedation)

–HelpsenhanceRLSfranchiseinwhichGSKinvested

heavilyRequip?(ropiniroleHCl)?GlaxoSmithKline?InitiallyApproved1997?GenericEntry2008

(MultipleCompanies)32Non-ConfidentialCobuzzi-UP3233Non-ConfidentialCobuzzi-UPenn–2December2008Solzira

Update

GSK

and

XenoPort

Announce

Plans

to

Withdraw

and

Resubmit

New

Drug

Application

Requesting

Approval

of

Solzira(TM)

for

Restless

Legs

Syndrome

RESEARCH

TRIANGLE

PARK,

N.C.

&

SANTA

CLARA,

Calif.,

Nov

10,

2008

(BUSINESS

WIRE)

GlaxoSmithKline(NYSE:GSK)andXenoPort,Inc.(Nasdaq:XNPT)

announcedtodaythattheNewDrugApplication(NDA)forSolzira(TM)

(gabapentinenacarbil)ExtendedReleaseTabletsforthetreatmentof

moderate-to-severeprimaryRestlessLegsSyndrome(RLS)hasbeen

withdrawn.TheUnitedStatesFoodandDrugAdministration(FDA)has

requestedthatthedatainasinglestudybereformatted.Inaddition,

GSKwillconductareviewofothertrialdatasetstakingthisinputinto

account.Thewithdrawaldoesnotrelatetothecontentofthefiling.GSK

planstoresubmittheNDAquicklyoncethisworkiscomplete.

TheresubmissionwillleadtoadelayinthereceiptbyXenoPortof

milestonepaymentsof$23millionintheaggregatefromGSKand

AstellasPharmaInc.,whichareassociatedwiththeacceptancebythe

FDAoftheNDAforSolzira.33Non-ConfidentialCobuzzi-UP3334Non-ConfidentialCobuzzi-UPenn–2December2008

Acqusition

Case

Study

‘Beauty

is

in

the

eye

…’AstraZenecaAcquisitionofMedimmune34Non-ConfidentialCobuzzi-UP3435Non-ConfidentialCobuzzi-UPenn–2December2008Third

Party

Press

Release

AstraZeneca

stock

falls,

MedImmune

surges

on

news

of

$15

billion

merger;

analysts

say

benefits

of

deal

won't

emerge

for

years.

By

Aaron

Smith,

CNNM

staff

writer

April

23

2007:

3:17

PM

EDT

NEW

YORK

(CNNM)

--

AstraZeneca's

stock

tumbled

Monday

after

the

company

said

it

would

pay

$15

billion

to

acquire

MedImmune,

a

deal

that

some

industry

analysts

are

calling

too

expensive,

and

risky.

The

deal's

near-term

benefit

is

limited,

analysts

say,

but

they

believe

the

deal

may

make

AstraZeneca

more

competitive

in

the

fast-growing

biotech

sector

in

years

to

come.

"The

rumor

of

MEDI

being

bought

has

been

in

the

market

for

several

weeks,

but

there

was

little

expectation

that

the

deal

would

be

as

big

as

it

is,"

wrote

Hamed

Khorsand,

analyst

for

BWS

Financial,

in

a

published

note.

AstraZeneca's

stock

slid

5

percent

following

the

announcement

while

MedImmune's

stock

surged

18

percent.

That's

on

top

of

MedImmune's

14

percent

stock

gain

on

April

12,

when

the

company

said

it

was

exploring

"strategic

alternatives,"

Wall

Street

code

for

considering

a

buyer.35Non-ConfidentialCobuzzi-UP35SanfordC.Bernstein36Cobuzzi-UPenn–2December2008Deal

Terms??$58

a

share

in

an

all-cash

$15.2

billiontransaction

–Offerrepresentsa20percentpremiumto

MedImmune'sstockpricedaybeforeclose

–50percentabovetradingpriceinearlyApril,before

thecompanypubliclysaiditwasputtingitselfupfor

saleHarshCommentary

–AstraZenecapaid$58asharebutonlyhadtopay

$44ashare"justtobreakeven"inachievingshort-

term

–Dealcouldpayofffiveor10yearswhen

MedImmune'svaccineplatformeventuallygivesthe

companyacompetitiveedgeinthefast-growing

biotechsector?GbolaAmusa,analystforinvestmentresearchfirm

Non-ConfidentialSanfordC.Bernstein36Cobuzzi3637Non-ConfidentialCobuzzi-UPenn–2December2008What

would

you

have

done????Whatwasthecommercial/unmetmedicalneedaddressedbytheacquisition?

–Wasthedealworththeprice?Doesthepipeline/productbenefitoutweightheriskprofileintheintendedindications?DoesthenewproducthaveIPorjustHatch-Waxmanexclusivity–i.e.,istheresufficienttimetorecouptheinvestment?37Non-ConfidentialCobuzzi-UP3738Non-ConfidentialCobuzzi-UPenn–2December2008AstraZeneca’s

problem??“Thoughhighlyprofitable,drugcompaniessuchasAstraZenecahavestruggledwithWallStreet'sconcernthattheylackastrong"pipeline,"orrosteroffuturedrugs.AstraZenecamarketssomeoftheworld'stop-sellingtreatments,includingCrestorforhighcholesterolandNexiumforheartburn,buthasstruggledtofinddrugsthatcouldbecomefutureblockbusters.Itabandoneddevelopmentofonepotentialheartdrugyesterdayafterdisappointingresultsinclinicaltrials.”

–StephenHeuser,BostonGlobe,April24,2007Additionalrealities––––Bigpharmareliesuponblockbusterdrugs(i.e.,sales>$750M–$1B)HigherhurdleswithsmallmoleculesincludegreatersafetyscrutinyGreaterspecificityofbiologicsperceivedassolutionBiologicscurrentlycommandahighersellingpriceduetocostofgoods,improvedoutcomesandlackofgenericpathway38Non-ConfidentialCobuzzi-UP3839Non-ConfidentialCobuzzi-UPenn–2December2008Problem

Solved?????MedImmune's"vast"pipelinemadeita"aprimetargettobeacquiredbyalargepharmaceuticalcompany.“

–AaronSmith,CNNMstaffwriterMulti-productportfolioandpipeline

–Synagis,treatmentforacommonrespiratoryvirus,accountedfor$1.1billionof

$1.2billioninannualsalesin2006

–Late-stagetrialsforNumax,next-generationofSynagiswereongoing

–NasalfluvaccineFluMistsold$36million

–Ethyol,adrugtoreducechemotherapysideeffects,sold$87millionAstraZenecaacquired“…alargestableofearly-stageresearchprojects,threemarketeddrugs,and20years'worthofexperiencedevelopingvaccinesandbiologicals,ordrugsproducedinlivingcells.”

–-StephenHeuser,BostonGlobe,April24,2007Onlytime(andstockprice)willtellifthiswasasuccessfuldeal39Non-ConfidentialCobuzzi-UP3940Non-ConfidentialCobuzzi-UPenn–2December2008AZN

2-year

Stock

Performance

StockPerformancevs.S&P500

DealAnnouncement

Adownwardtrend,yes…but,companysizemakesrootcauseanalysisdifficult40Non-ConfidentialCobuzzi-UP4041Non-ConfidentialCobuzzi-UPenn–2December2008ANY

QUESTIONS?41Non-ConfidentialCobuzzi-UP41Our

PatientsOur

PeopleOur

Business