摩根士丹利-ESMO会议将聚焦多款关键创新抗癌药物-ESMO Conference will spotlight a number of key innovative cancer drugs-20260930

RESEARCH

Morganstanley

September30,202608:30PMGMT

Biopharma|NorthAmerica

ESMOConferencewillspotlightanumberofkeyinnovative

cancerdrugs

TheESMOcancerconference(Oct23-27)inMadridwillincludeanumberofimportantpresentationsforthelatestinnovativecancermedicinesindevelopment.

KeyTakeaways

MRNA/MRK–INTPh3mel:RFSHRiskey;priorKOLcallindicated≤0.75exciting,whileideallylookingfor≤0.65.ButPh2RCC/MIBCdatalikelymoreimportant.

MRK/Kelun–Sac-TMT+KeytrudainLung06:FocusonPFSHR(likelystronggivenhitatinterimandOStrend)andcontrolarmperformancevs.KN-189(6.2mo

mPFS).

MRK/Kelun–TroFuse-005Ph3endometrial:OSHR~0.7-0.8wouldbeclinicallymeaningfulinpost-platinum/post-IOsetting;andgeographicconsistencyalsoafocus

JNJ–ForRybinHNC,focusonORR/PFSvs.~36%/4.9moSOC.ForRIPTACinprostate,PSA50/90,RECISTresponses,durabilityandsafetyattheselecteddose.

PFE–Atirmo(CDK4)Ph2breast:WithPFSHR0.6disclosed,focusshiftsto

absolutemPFSbenefit/tolerability;differentiationvs.establishedCDK4/6iiskey.

WeanticipateseveralimportantupdatesacrossourcoverageatESMOcancer

conference(Oct23-27),withourfocusonnewdataforMRK/MRNA'sintismeranautogene(INT)inmelanoma,MRK/Kelun'ssac-TMT(TROP2ADC)acrosslung,endometrialandbreastcancer,JNJ'sRybrevantin1Lheadandneckcancer,PFE'sAtirmo(CDK4i)inbreastcancer,AMGN'sImdelltra(BiTEtoDLL3)in1LSCLC,

andBHVN's'1530(FGFR3ADC).Withinwehighlightthepresentationswearewatchingandoutlinekeyquestions/focusareasandrelevantbenchmarks.

KeluniscoveredbyAlexisYan.

IDEA

MoRGANSTANLEy&Co.LLC

TerenceCFlynn,Ph.D.

EquityAnalyst

Terence.Flynn@

+1212761-2230

HaileyHorowitz

ResearchAssociate

Hailey.Horowitz@

ChrisYu,J.D.,Ph.D.

EquityAnalyst

+1212761-5264

Chris.L.Yu@

+1212761-2535

ConnorMMassari

EquityAnalyst

Connor.Massari@

+1212761-2417

AlexanderYevdokimov,Ph.D.

ResearchAssociate

Alexander.Yevdokimov@

+1212761-2167

DamienHKerner

ResearchAssociate

Damien.H.Kerner@

+1212761-3829

MoRGANSTANLEyINDiACompANyPRivATELimiTED+SaketAgarwal

ResearchAssociate

Saket.Agarwal@

+91226995-4012

MorganStanleydoesandseekstodobusinesswith

companiescoveredinMorganStanleyResearch.Asaresult,investorsshouldbeawarethatthefirmmayhaveaconflictofinterestthatcouldaffecttheobjectivityofMorganStanley

Research.InvestorsshouldconsiderMorganStanley

Researchasonlyasinglefactorinmakingtheirinvestmentdecision.

Foranalystcertificationandotherimportantdisclosures,refertotheDisclosureSection,locatedattheendofthisreport.

+=Analystsemployedbynon-U.S.affiliatesarenotregisteredwithFINRA,maynotbeassociatedpersonsofthememberandmaynotbesubjecttoFINRArestrictionson

communicationswithasubjectcompany,publicappearancesandtradingsecuritiesheldbyaresearchanalystaccount.

2

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MRNA/MRK'sintismeranautogene(lNT)Ph3melanomadata

Presentationtitle:INTerpath-001:Phase3studyofthemRNA-basedindividualized

neoantigentherapy(INT)intismeranautogene(intismeran)pluspembrolizumab(pembro)vspembroaloneforadjuvanttreatmentofresectedstageIIB-IVmelanoma

Date&Time:Saturday,October24,10:30AMET.MRNAwillalsohostaninvestorwebcastonSaturday,October24,at1:00PMET.MRKwillalsohostawebcaston

Monday,October26toreviewpresentationsatESMO,includingforINTandsac-TMT(below).

MRNA/MRKwillpresentthefulldatafromthePh3INTerpath-001studyevaluating

intismeranautogene(INT)+Keytrudavs.Keytrudaaloneasadjuvanttherapyinpatients

withcompletelyresectedStageIIB-IVmelanoma.RecallMRNA/MRKreportedpositive

toplinedatainAugust'26,withthestudymeetingitsprimaryRFSendpointandkey

secondaryDMFSendpoint,demonstratingstatisticallysignificantandclinicallymeaningfulimprovementsonboth(LINK).Thecompanieshavenotdisclosedthemagnitudeof

benefit,makingtheRFSHRthekeyfocusatESMO.Wemodelrisk-adjustedsalesof~$14bnforINT(or~$20bnunadjusted)acrossindications.SeeourrecentdeepdiveHEREandKOLfeedbackHERE.

Whatarewelookingfor?

KOLfeedbacksuggestsRFSHR≤0.75wouldbeexcitingbutideallylookingfor≤0.65.InvestorfeedbacksuggestsaHRof0.6Xwouldbeviewedfavorably.OurframeworkisinformedbythePh3studyhittingataninterimanalysisandthepriorPh2experience,

whereINT+Keytrudademonstrateda44%relativereductioninrecurrence/deathattheinitialreadoutandasustainedRFSbenefitatfive-yearfollow-up(HR=0.51).Acancer

immunotherapyKOLwerecentlyhostedviewsRFSasastrongsurrogateforcurein

adjuvantmelanomaandwouldconsideranRFSHR≤0.75exciting,whileideallylookingfor≤0.65;healsoexpectsthepositiveRFSresulttoultimatelytranslateintoanOSbenefit.Atourrecenthealthcareconference,MRNA/MRKpointedtothepositivePh3adjuvant

melanomaresultanddurablefive-yearPh2dataasincreasingconfidenceintheunderlyingT-cellpriminghypothesisanddurabilityofbenefit(LINK).BothcompaniesemphasizedtheopportunitytomoveINTintoearlier-stagedisease,withMRNAcallingadjuvant/earlier

settingsthemostfruitfulplacetointerveneandMRKnotingthatINT’scleansafetyprofilesupportsexploringsettingssuchasStageIlung(wherethereisatrialinprogressposteratESMO).MRNAalsohighlightedfavorablePh2melanomaHRsregardlessofTMBorPD-L1status,suggestingINTmaynotfollowtypicalcheckpoint-inhibitorbiomarkerparadigms.BeyondtheheadlineHR,wewillfocusontheabsoluteRFS/DMFSbenefit,consistency

acrossclinicallyrelevantsubgroups,andanyavailableOSdata.

MRNA/MRKaredevelopingINTacrosssixtumortypes,withPh2adjuvantRCCandMIBCamongthenextimportantproofpoints(dataexpectedlate'26/2027forRCCand2027forMIBC).OurKOLexpectsefficacytotranslatebeyondmelanoma,albeitpotentiallywith

attenuationinlessimmunogenictumors,andviewstheadjuvantsettingasparticularlywellsuitedtothisapproachgivenlowertumorburdenandamorefavorableimmuneenvironment.

Morganstanley

RESEARCH

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MRK/Kelun'sSac-TMT(TROP2ADC)

OptiTROP-Lung061LPD-L1-negativeNSQNSCLCdata

Presentationtitle:Sacituzumabtirumotecan(sac-TMT)pluspembrolizumab(P)versuschemotherapy(chemo)pluspembrolizumab(P)asfirst-line(1L)treatmentforPD-L1

negativeadvancednon-squamous(nsq)NSCLC:randomizedphase3OptiTROP-Lung06study.

Date&Time:Sunday,October25,5:53amET.MRKwillalsohostawebcastonMonday,October26at2:30pmETtoreviewpresentationsatESMO,includingforsac-TMTandINT(above).

OptiTROP-Lung06isaChinaPh3study(n=432)evaluatingsac-TMT(TROP2ADC;

partneredwithKelun)+Keytrudavs.Keytruda+pemetrexed/platinumchemotherapyin1Llocallyadvanced/metastaticnon-squamousNSCLCwithPD-L1TPS<1%.Kelun

previouslyannouncedthatatthepre-specifiedinterimanalysis,sac-TMT+KeytrudademonstratedastatisticallysignificantandclinicallymeaningfulPFSbenefit,withapositiveOStrendandnonewsafetysignals(LINK).Wemodel~$7bnof2035risk-adjustedsac-TMTsalesacrossindications,including~$3.8bninlungcancer.

Whatarewelookingfor?ThePFSHRandperformanceoftheKeytruda+chemocontrolarmarethetwomostimportantdatapoints.KEYNOTE-189providestheclosesthistoricalbenchmark:inthePD-L1<1%subgroup,Keytruda+pemetrexed/platinumdeliveredmPFSof6.2months,a12-monthPFSrateof27%,andmOSof17.2months;Exhibit1.MRK

managementhasindicatedon2QEPSthatitiscomfortablewiththeLung06dataset,includingcontrol-armperformance,andnotedthatthestudy’ssuccessincreases

confidenceinsac-TMTacrossthe“fullspectrum”ofPD-L1expression.Beyondthe

headlinePFSHR,wewillfocusontheabsolutemPFSbenefit,OStrend,ORR/DoRandtolerabilityvs.Keytruda+chemo.WewouldalsowatchbaselinecharacteristicsgiventheChina-onlypopulationandtheircomparabilitywithglobal1LNSCLCepidemiology.

ThedatasetshouldalsohelpinformMRK’sglobaldevelopmentstrategyinthelargePD-L1<50%population.FollowingthepositiveChinaLung05andLung06readouts,webelieveMRKisincreasinglylikelytoexpandsac-TMTintoPD-L1<50%NSCLC,whichrepresentsroughlytwo-thirdsofKeytrudalungcancersales,althoughtheeventualregimenremainsanopenquestion.Atourrecentconference,MRKpositionedsac-TMTasadifferentiatedTROP2ADCandpotentiallunganchoracrossPD-L1expressionlevels,withthekey

strategicquestionbeingwhentocombinewithKeytrudavs.MK-2010(PD-1×VEGFbispec);LINK.SeveralongoingPh2combinationstudiesaredesignedtotransitionseamlesslyintoPh3,whichshouldprovidegreaterclarityonregimenselectionoverthenext12-18mos.

ManagementalsonotedthatbiomarkersareavailableforitsADCprogramsbutwouldbedeployedonlywheresupportedbythedata,andsaiditwillcloselyscrutinize

AstraZeneca/Daiichi'supcomingglobalDato(TROP2ADC)Ph3AVANZARreadout—

includingtheall-comersandQCSbiomarkerresults—asanexternalbenchmarkforits

ownstrategy.WeexpectLung06,AVANZARandemergingPD-1xVEGFdatatocollectivelyinformtheoptimalregimenandwhetherabiomarkerstrategyiswarranted.

MoRGANSTANLEyREsEARcH3

4

IdEA

Exhibit1:KeytrudaKEYNOTE1LNSCLCdatasummaryacrossPD-L1expressionlevels

Trial

Population

KEYNOTE-189

(5-yrfollow-up)1LNSQNSCLC

KEYNOTE-407

(5-yrfollow-up)1LSQNSCLC

KEYNOTE-042

(5-yrfollow-up)1LNSCLC

KEYNOTE-024

(5-yrfollow-up)1LNSCLC

Arm

Keytruda+chemo

Chemo

Keytruda+chemo

Chemo

Keytruda

Chemo

Keytruda

Chemo

PD-L1≥50%

n

132

70

73

73

299

300

154

151

mPFS(mos)

11.3

4.8

8.3

4.2

6.5

6.5

7.7

5.5

12-moPFSrate

49%

17%

37%

15%

~35%*

~30%*

~40%

~15%

mOS(mos)

27.7

10.1

19.9

11.5

20.0

12.2

26.3

13.4

PD-L11-49%

n

128

58

103

104

338

337

mPFS(mos)

9.4

4.9

8.2

6.0

12-moPFSrate

44%

21%

40%

19%

mOS(mos)

21.8

12.1

18.0

13.1

13.4*

12.1*

PD-L1≥1%

n

mPFS(mos)

12-moPFSratemOS(mos)

637

5.6

~30%*

16.4

637

6.8

~30%*

12.1

PD-L1<1%

n

127

63

95

99

mPFS(mos)

6.2

5.1

6.3

5.9

12-moPFSrate

27%

16%

32%

21%

mOS(mos)

17.2

10.2

15.0

11.0

PD-L1all-comers

n

410

206

278

281

mPFS(mos)

9.0

4.9

8.0

5.1

12-moPFSrate

40%

18%

36%

19%

mOS(mos)

22.0

10.6

17.2

11.6

MostsimilartoLung-06controlMostsimilartoLung-05control

Source:MorganStanleyResearch,Garassinoetal,JCO2023(KN-189),Novelloetal,JCO2023(KN-407),Recketal,JCO2021(KN-024),Castroetal,JCO2022(KN-042);*Fromearliercut(Moketal,ELCC2019)

Exhibit2:Overviewofselect1LmetastaticNSCLCtrial

Histology

Squamous

Both

Non-Squamous

PD-L1≥50%

All-comers

(PD-L1-High)

KEYNOTE-407(MRK)☑

Key+chemovs.Chemo

Symbiotic-Lung-01(PFE)→

PF-4404+chemovs.Key+chemo

PCDFeb'29

IMpower150(Roche)☑

Tecentriq+/-Avastin+chemovs.

Avastin+chemo

HARMONi-6(SMMT/Akeso)☑→

Ivo+chemovs.Tevimbra+chemo

PositivePFSdata10/19/25

OSdatapresentedatASCO'26

ROSETTA-Lung02(BNTX/BMY)→

Pumi+chemovs.Key+chemo

Ph2datapresentedatASCO'26

HARMONi-3(SMMT/Akeso)→CheckMate9LA(BMY)☑Ivo+chemovs.Key+chemo

Opdivo+Yervoy+chemovs.ChemoSQ:PFS&interimOS2H26;

NSQ:finalPFS1H27

KEYNOTE-024(MRK)☑

Keyvs.Chemo

Be6ALung-02(PFE)→

SV+Keyvs.KeyPCDofSept.'28

HARMONi-7(SMMT/Akeso)→

Ivovs.Key

PCDofApr.'28

TroFuse-007(MRK/Kelun)→

Sac-TMT+Keyvs.Key

KEYNOTE-189(MRK)☑

Key+chemovs.Chemo

AVANZAR(AZN/Daiichi)→

Dato+Imfinzi+chemovs.Key+chemo

Toplinedatain2H26

PD-L1Status

PD-L1≥1%

PD-L1<1%

(PD-L1-Positive)

(PD-L1-Negative)

ARTEMIDE-Lung02(AZN)→

rilvegostomig+chemovs.Key+chemo

PCDFeb.'29

EVOKE-03(GILD)⮽

Trodelvy+Keyvs.KeyTrialdiscontinued

TROPION-Lung08(AZN/Daiichi)→

Dato+Keyvs.Key

Dataexpected~2H26

IMpower110(Roche)☑

KEYNOTE-042(MRK)☑

Tecentriqvs.Chemo

Keyvs.Chemo

ApprovedinPD-L1≥50%

OptiTROP-Lung05(MRK/Kelun)☑→

Sac-TMT+Keyvs.Key

PFSstat.sig.,OStrend11/24/25FulldatapresentedatASCO'26

CheckMate227(BMY)☑

Opdivo+Yervoyvs.ChemoPart1aoftrial;PD-L1≥1%

HARMONi-2(SMMT/Akeso)☑→

Ivovs.Key

PositivePFSandinterimOS4/25/25

AwaitingmatureOS

TROPION-Lung07(AZN/Daiichi)→

(PD-L1<50%)

Dato+Key±chemovs.Key+chemo

Dataexpectedin2027

OptiTROP-Lung06(MRK/Kelun)→

Sac-TMT+Keyvs.Key+chemo

Positivetopline7/14/26

InterimdataatESMO'26

→Ongoing

☑PositiveUpdate

⮽NegativeUpdate

Near-termfocus

Recentlyreported

Source:Companydata,

CT.gov

,MorganStanleyResearch

TroFuse-005endometrialdata

Presentationtitle:SacituzumabTirumotecaninPreviouslyTreatedAdvancedor

RecurrentEndometrialCancer:ResultsfromthePhase3TroFuse-005/ENGOT-en23/GOG-3095Study

Date&Time:Monday,October26,12:18pmET.

MoRGANSTANLEyREsEARcH5

Morganstanley

RESEARCH

IDEA

Recall,MRKannouncedinMay'26thatTroFuse-005metbothOSandPFSprimary

endpoints,makingitthefirstglobalPh3studytodemonstratestatisticallysignificant

improvementsinbothendpointsvs.chemotherapyinpost-platinum/post-PD-(L)1

endometrialcancer(LINK).Thecompanypreviouslyannounceditisusingsac-TMT's

Commissioner’sNationalPriorityVoucher(CNPV)ontheendometrialcancerfiling,whichtargetsanFDAdecisionwithin1-2monthsfollowingsubmissionofacompleteapplication.Ifapproved,TroFuse-005willrepresentsac-TMT'sfirstUSindication,thoughwemodelamodestlaunchduetoarelativelysmallopportunityhere-ourglobalsac-TMTmarket

modelisavailableuponrequest.

Whatarewelookingfor?ThemagnitudeoftheOSbenefit,performanceofthe

physician’s-choicechemotherapycontrolarm,andconsistencyofdataacrossgeographicsubsetswillbethekeyfocus.KEYNOTE-775providesthemostrelevanthistorical

benchmark,wherephysician’s-choicedoxorubicin/paclitaxelproducedmOSof~12months,whileKeytruda+LenvimadeliveredmOSof17.4monthsandanOSHRof0.68intheall-comerpopulation.However,TroFuse-005enrolledalater-linepopulationthatwas

requiredtohavereceivedbothpriorplatinumchemotherapyandPD-(L)1therapyandalsopermitscarcinosarcoma,makingtheKEYNOTE-775chemotherapyarmanimperfect,andpotentiallyoptimistic,controlbenchmark.Againstthisbackdrop,wethinkanOSHRinthe~0.70-0.80rangewouldtranslateintoaclinicallymeaningfulbenefit,whiletheabsolutemediangainwilldependheavilyoncontrol-armperformance.IfcontrolmOSiscloserto9-10months,anHRof0.70-0.80wouldimplyroughlya2.5-4monthimprovementunderaproportional-hazardsassumption.BeyondtheheadlineOSresult,wewillfocusonPFS,ORR/DoR,consistencyacrosshistology/MMRandprior-treatmentsubgroups,and

tolerability,particularlywhetherthedepthanddurabilityofbenefitsupportsac-TMTasameaningfulpost-IOoptionacrossabroadendometrialcancerpopulation.Forreference,mPFSwas6.6mosforKeytruda+LenvimainKN-775vs.3.8mosforchemo.Weand

investorswillalsobefocusedonconsistencyofefficacyacrossgeographicsubsetsgivenongoingquestionsabouttranslatabilityofdatafromChinatoWesternpopulations.Per

CT.gov

,~18%ofthetrial'ssitesareintheUS,with23%inAsia(n=242sitestotalacross710patientsenrolled),andthusweexpecttherecouldbeinsightonthisquestion.

6

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Exhibit3:Sac-TMTregistrationalprogramsummary

TrialComparator(s)PopulationPrimaryEndpointPrimarycompletion

Sac-TMT

TroFuse-0043LEGFRmNSCLCPFS.OSMay'27

vs.chemo

Sac-TMT+Key

TroFuse-007

1LPD-L1TPS≥50%NSCLCOSJanuary'28

vs.Key

NSCLC

Sac-TMT

PFS,OS

DFS

September'28

February'34

January'29

TroFuse-009

TroFuse-019

TroFuse-023

2LNSQEGFRmNSCLC

vs.chemo

Sac-TMT+Key

AdjuvantNSCLC(nopCRpostsurgery)

vs.Key

Sac-TMT+Key

OS

SQmNSCLCmaintenance(postKeytruda+chemo)

vs.Key

Sac-TMT+/-Key

TroFuse-010

HR+/HER2-unresectableLAormBCPFSJuly'27

vs.TPCchemo

east

Sac-TMT+/-Key

TroFuse-011

LA/mTNBCPD-L1atCPS<10PFS,OSMay'30

vs.TPCchemo

Br

Sac-TMT+Key

TroFuse-012

TNBCdidnotachievepCRatsurgeryiDFSDecember'30

vs.TPCKey+/-chemo

Sac-TMT+Key+chemo+TPCvs.Key+chemo+TPC

TroFuse-032

NeoadjuvantTNBCorHR-low/HER2-BCpCR,EFSMarch'33

January'28

positivetoplinereported

Sac-TMT

TroFuse-005

Postplatinum&I/OendometrialcancerPFS,OS

vs.chemo

ncers

Sac-TMT+Key

TroFuse-033

pMMRendometrialcancerPFS,OSMay'32

vs.Key

icCa

Sac-TMT

TroFuse-020

orchemo2LmetastaticcervicalcancerORR,OSJune'28

vs.TPCTivdak

g

necolo

TroFuse-036

Sac-TMT+Key+/-Avastinvs.Key+/-Avastin

1LPD-L1+maintenancecervicalcancerPFS/OSOctober'31

Gy

TroFuse-021

Sac-TMT+Avastinvs.Avastin

Non-HRDpositiveadvancedovariancancerPFSFebruary'33

TroFuse-022

Sac-TMT+Avastinvs.Avastin

PlatinumsensitiverecurrentovariancancerPFSApril'29

Sac-TMT

her

TroFuse-031LA/m2-4LUCpostKeytruda/Padcev/chemoOSJuly'29

vs.chemo

Ot

Sac-TMT

TroFuse-015

3L+adv./met.adenocarcinomaOSJanuary'27

chemo

vs.TPC

Source:Companydata,

CT.gov

,MorganStanleyResearch

Presentationtitle:FinalOSanalysisofsacituzumabtirumotecanversuschemotherapyinpreviouslytreatedlocallyrecurrentormetastatictriple-negativebreastcancer(TNBC):PhaseIIIOptiTROP-Breast01

Date&Time:Monday,October26,5:15amET.

WhilewebelievetheLung06andTroFuse-005presentationsabovewillbemorefocal,finalOSdatafromthePh3China-onlyOptiTROP-Breast01studyprovideanadditionaldatasetforsac-TMTinheavilypretreatedTNBC.Thestudyevaluatessac-TMTvs.

physician’s-choicechemoinpatientswithlocallyrecurrent/metastaticTNBCfollowing≥2priorsystemictherapies,including≥1inthemetastaticsetting.ThemostmatureefficacydatatodatehavedemonstratedasubstantialPFSbenefit.AtthefinalPFSanalysis,

medianBICRPFSwas6.7mosforsac-TMTvs.2.5mosforchemotherapy(HR0.32).ThiswasconsistentwiththeinitialASCO2024analysis,wheremedianPFSwas5.7mosvs.

2.3mos(HR0.31).Importantly,thefirstprespecifiedOSinterimanalysishadalready

crossedtheefficacyboundary:at10.4mosmedianfollow-up,mOSwasnotreachedforsac-TMTvs.9.4mosforchemotherapy,withanOSHRof0.53(95%CI0.36–0.78;

p=0.0005).

Whatarewelookingfor?ForESMO,weviewmatureOSasthekeyreadout,with

particularfocusonwhethertheHRremainsinthe~0.5–0.6rangedespitetherelativelystrongcontrol-armOS.The9.4moscontrol-armmOSattheinterimanalysisisnotableinthisheavilypretreatedpopulationandmakestherelativetreatmenteffectarguablymoreinformativethanasimplecross-trialcomparisonofmOS.Giventhemagnitudeand

consistencyofthePFSbenefit(HR~0.3)andthealreadystatisticallysignificantinterimOS(HR0.53),expectationsareforthefinalanalysistoconfirmaclinicallymeaningful

survivaladvantage.ThedegreetowhichtheOSHRismaintainedaseventsmaturewillbetheprincipalquestion,alongwithmOSforsac-TMT,landmarksurvivalratesandshape/separationoftheupdatedKaplan-Meiercurves,astheseshouldprovideabettersenseof

MoRGANSTANLEyREsEARcH7

Morganstanley

RESEARCH

IDEA

whetherthepronouncedearlydisease-controlbenefittranslatesintodurablesurvival.

Cross-trialcomparisonsremainimperfect,particularlygiventhatOptiTROP-Breast01is

China-only,butwe'dpointtoGILD'sTrodelvyASCENTtrialasthemostsimilarpopulation(mOSof12.1vs.TPCcontrol6.7mos,HR~0.50;LINK).Inaddition,we'dnotethatasofanearliercut,71%ofpatientsinthechemoarmhadreceivedsubsequentanticancertherapy,including15%withaTROP2ADC,whichcouldbeacontributortothestrongercontrol

armOSperformanceonacross-trialbasis.

8

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IdEA

JNJ'sRybrevantforHNCandRIPTACforprostatecancer

Rybrevantin1LHNSCC

Presentationtitle:Amivantamab+pembrolizumab+carboplatininfirst-linerecurrent/metastatichead&necksquamouscellcancer(1LR/MHNSCC):Resultsfromthephase1b/2OrigAMI-4study

Date&Time:Sunday,October25,10:12amET.

AtESMO,JNJwillpresentresultsfromthePh1b/2OrigAMI-4studyevaluatingRybrevant(amivantamab)+Keytruda+carboplatininpreviouslyuntreatedrecurrent/metastatic

headandnecksquamouscellcarcinoma(R/MHNSCC);Cohort5.ThetripletrepresentstheregimenJNJisadvancingintotherandomizedPh3OrigAMI-5study,whereitisbeingcomparedwiththecurrentKeytruda+platinum+5-FUregimen(PCDofJune'29).

Whatarewelookingfor?PriorOrigAMI-4dataprovideanencouragingefficacybarfor

thetriplet:SQRybrevant+Keytrudademonstrateda56%confirmedORR,including10%CRs,andmPFSof7.7monthsin1LPD-L1-positive,HPV-unrelatedR/MHNSCC(Cohort2;LINK).Theupcomingdatasetaddscarboplatintothisbackbone,andwewillbelookingforwhetherchemotherapycanfurtherdeepenresponsesandextendPFSwithoutanoutsizedincreaseintoxicity.ThemostrelevantSOCbenchmarkisKeytruda+platinum-based

chemotherapyfromKEYNOTE-048,whichdeliveredanORRof~36%,mPFSof4.9

monthsandmOSof13.0monthsintheall-comerpopulation;inPD-L1CPS≥1patients,

ORRwas~36%andmOS13.6months.Ausefulcontemporary5-FU-freebenchmarkis

KEYNOTE-B10,whereKeytruda+carboplatin+paclitaxelproduceda49%ORR,5.6-

monthmPFSand13.1-monthmOS,albeitinasingle-armstudy.Againstthosebenchmarks,wewillfocusonORR/CRrateanddepthofresponse,whetherPFSimprovesmeaningfullyonthe7.7monthsalreadyobservedwiththeRybrevant+Keytrudadoublet,and

ultimatelyDoR/OSasthedatamature.Safetywillalsobeimportantgiventhe

incrementaltoxicityfromlayeringchemotherapyontothedoublet,particularlywhetherthemagnitudeofefficacybenefitissufficienttojustifyathree-drugregimen.

RybrevantisalreadyapprovedacrossmultipleEGFRmNSCLCsettings,includingin

combinationwithLazcluze(EGFRTKI)for1L,whereitdemonstratedastatistically

significantandclinicallymeaningfulOSimprovementvs.AZN'sTagrisso(LINK).Rybrevant+LazcluzeremainsoneofJNJ's$5bn+pipelineproducts,andmgmtpreviouslyprojectedthe1LEGFRmarketcouldgrowto$10bn(LINK);wemodel2030/2035salesof$7.2bn/$9.0bn,withsuccessintumorsbeyondlungrepresentingpotentialupside.

JNJ-6143(oralARRIPTAC)Ph1prostatecancerdata

Presentationtitle:SafetyandefficacyofJNJ-6143,afirst-in-classoralAR-targetedregulatedinducedproximitytargetingchimeraattheoptimaldoseforfurther

developmentinpatientswithmCRPC/mAPMR,includinghigh-riskmolecularfeaturesDate&Time:Saturday,October24,4:25amET.

JNJwillpresentupdatedPh1/2dataforJNJ-6143(oralAR-targetedRIPTACfromHalda)inpatientswithmCRPC/mAPMR,includingpatientswithhigh-riskmolecularfeatures.

MoRGANSTANLEyREsEARcH9

Morganstanley

RESEARCH

IdEA

RIPTACsworkbybringingatumor-specificprotein(androgenreceptor/ARforJNJ-6143)

togetherwithanessentialcellularprotein(BRD4),formingaternarycomplexthat

disruptsBRD4functionandselectivelykillsAR-expressingcancercells.InitialFIHdata

fromthetrialwerepresentedpriortotheacquisitionatAACR-NCI-EORTC2025and

showedencouragingearlyactivitydespiteaheavilypretreatedpopulation.Across31

patientstreatedat12.5–100mg,PSA50/90responseswere42%/23%overalland

59%/32%amongthe22patientswhohadreceived≥2cycles;allfiveRECIST-evaluable

patientswithmeasurablediseaseachievedaPR.Activityappearedstrongestat50mg,

wherePSA50was50%overalland70%amongpatientsreceiving≥2cycles.JNJ

highlightedatourrecenthealthcareconferencethatthedrugis"extremelywelltolerated"andismovingintoPh3development(LINK).Mgmtseesitaspotentiallypractice-changin