阿斯利康 減重領(lǐng)域介紹 AZN Meet the Management Weight Management Virtual Event

AZNMeettheManagement:

WeightManagementVirtualEvent

Webinarforinvestorsandanalysts

4November2024

2

Forward-lookingstatements

Inorder,amongotherthings,toutilisethe‘safeharbour’provisionsoftheUSPrivateSecuritiesLitigationReformActof1995,AstraZeneca(hereafter‘theGroup’)providesthefollowingcautionarystatement:Thisdocumentcontainscertainforward-lookingstatementswithrespecttotheoperations,performanceandfinancialconditionoftheGroup,including,amongotherthings,statementsaboutexpectedrevenues,margins,earningspershareorotherfinancialorothermeasures.AlthoughtheGroupbelievesitsexpectationsarebasedonreasonableassumptions,anyforward-lookingstatements,bytheirverynature,involverisksanduncertaintiesandmaybeinfluencedbyfactorsthatcouldcauseactualoutcomesandresultstobemateriallydifferentfromthosepredicted.Theforward-lookingstatementsreflectknowledgeandinformationavailableatthedateofpreparationofthisdocumentandtheGroupundertakesnoobligationtoupdatetheseforward-lookingstatements.TheGroupidentifiestheforward-lookingstatementsbyusingthewords‘a(chǎn)nticipates’,‘believes’,‘expects’,‘intends’andsimilarexpressionsinsuchstatements.Importantfactorsthatcouldcauseactualresultstodiffermateriallyfromthosecontainedinforward-lookingstatements,certainofwhicharebeyondtheGroup’scontrol,include,amongotherthings:theriskoffailureordelayindeliveryofpipelineorlaunchofnewmedicines;theriskoffailuretomeetregulatoryorethicalrequirementsformedicinedevelopmentorapproval;theriskoffailuresordelaysinthequalityorexecutionoftheGroup’scommercialstrategies;theriskofpricing,affordability,accessandcompetitivepressures;theriskoffailuretomaintainsupplyofcompliant,qualitymedicines;theriskofillegaltradeintheGroup’smedicines;theimpactofrelianceonthird-partygoodsandservices;theriskoffailureininformationtechnologyorcybersecurity;theriskoffailureofcriticalprocesses;theriskoffailuretocollectandmanagedatainlinewithlegalandregulatoryrequirementsandstrategicobjectives;theriskoffailuretoattract,develop,engageandretainadiverse,talentedandcapableworkforce;theriskoffailuretomeetregulatoryorethicalexpectationsonenvironmentalimpact,includingclimatechange;theriskofthesafetyandefficacyofmarketedmedicinesbeingquestioned;theriskofadverseoutcomeoflitigationand/orgovernmentalinvestigations;intellectualproperty-relatedriskstotheGroup’sproducts;theriskoffailuretoachievestrategicplansormeettargetsorexpectations;theriskoffailureinfinancialcontrolortheoccurrenceoffraud;theriskofunexpecteddeteriorationintheGroup’sfinancialposition;theimpactthatglobaland/orgeopoliticaleventsmayhaveorcontinuetohaveontheserisks,ontheGroup’sabilitytocontinuetomitigatetheserisks,andontheGroup’soperations,financialresultsorfinancialcondition.Nothinginthisdocument,oranyrelatedpresentation/webcast,shouldbeconstruedasaprofitforecast.

WeightManagement@AstraZeneca

I.WeightManagement@AZN

-Introductionandgrowthambitions

-Weightmanagementlandscape

-Ourweightmanagementstrategy

MikhailKosiborod,MDVP,Research@SaintLuke’sHealthSystem,KansasCity

SharonBarr

EVP,BioPharmaceuticalsR&D

II.PipelineHighlights

-AZD5004|oralGLP-1receptoragonist

-AZD6234|long-actingamylin

-AZD9550|GLP-1/glucagonagonist

ElisabethBj?rkSVP,LateCVRM

ReginaFritscheDanielsonSVP,EarlyCVRM

III.SummaryandQ&A

CVRMLeadershipTeam

l

3

Ambition-$80bnTotalRevenueby2030&sustained2030+growth

Workingon“today,tomorrowandthedayafter"

Beyond2030

Illustrativeonly,nottoscale

ADCsandRadioconjugates

$80bn

LaunchingkeyNMEs

rilvegostomigsaruparib

volrustomigAZNADCs

AZD0120

AZD0486

camizestrantDato-DXd

CelltherapyandT-cellengagers

Genetherapy

Next-generationIObispecifics

Existingportfolio

Weightmanagementandriskfactors

baxdrostatdapaFDCs

IVX-A12

tozorakimab

TagrissoTruqap

CalquenceEnhertu

efzimfotasealfaeneboparatide1

$45.8bn

Imfinzi/Imjudo

Airsupra

Saphnelo

Breztri

Tezspire

FasenraLokelma

Wainua

IRAimpact

Ultomiris

LossofExclusivity

BrilintaLynparzaFarxigaSoliris

2030TotalRevenueambitionnotdependentuponfutureM&A

2030

2023

Note:Ambitiontoachieve$80bninTotalRevenueby2030isrisk-adjusted,basedonlatestlong-rangeplan–seeslide3fordetails.Medicinesandassetslistedreflectkeycontributorsto2030TotalRevenueambition;however,thislistisnotexhaustive.Medicinesandassetslistedinalphabeticalorderandsortedbytherapyarea.1.AmolytPharmaacquisitionremainssubjecttocustomaryexternalclearances;allclinicaldevelopmentplansmentionedhereinsubjecttodeal

4closure.Collaborationpartners:DaiichiSankyo(Enhertu,Dato-DXd),Amgen(Tezspire),Ionis(Wainua),Compugen(rilvegostomig),Merck&Co.,Inc.(Lynparza).

5Partners:Amgen(Tezspire)andIonis(Wainua).AcronymdefinitionscanbefoundinGlossary.

BioPharmaceuticals-nextwaveofgrowth

to2030andbeyond

Beyond2030

Illustrativeonly,nottoscale

LaunchingNMEs

baxdrostatdapaFDCstozorakimabIVX-A12

Existingportfolio

M

RSUPR

A

紀(jì)Fasenra'

TEZSRTM

PE

ph

S

e

TM

Lossofexclusivity

BrilintaFarxiga

Amyloidosiscombinations

toaddressfullspectrumofdisease

Weightmanagement

andriskfactors

Expandingmodalities

inrespiratorycare

Auto-immunedisease

Celltherapy,T-cellengagersCAR-Treg

2023

2030

MikhailKosiborod,MD

VP,Research@SaintLuke’sHealthSystem,KansasCity

-PhysicianleaderoverseeingstrategicdirectionforallactivitiesacrosstheAcademicResearchOrganization

-DesignedandledclinicaltrialsthatmadecriticalcontributionstounderstandingtheimpactofSGLT2inhibitionandGLP-1receptoragonisminimprovingcardiovascularoutcomesandsurvival,

representingsomeofthemostimportantadvancesinclinicalmedicineinthelasttwodecades

-DirectorofSaintLuke’sHavertyCardiometabolicCenterof

ExcellenceandCardiometabolicCenterAlliance–ahighly

innovativeclinicalcaremodel,dedicatedtoproviding

comprehensiveriskreductiontopatientswithcardiometabolicdisease—since2019

6

71.TriNetX(USEHRdata),November2020andOptumclaimsdata.ObesitydefinedasICD10codesE66.0,E66.1,E66.2,E66.8,E66.9.ObesitydefinedasBMI>30,OverweightasBMI25-29.9.2.CurrentFDA/EMAguidanceis27-30BMI.BMI=bodymassindex.

LandscapeandStrategy

Sustainableweightmanagementisessential

forcardiometabolicorganprotection

Obesity

BMI:>30

Riskfactors

Underlyingconditions

63%

ofobesity

populationhas≥1co-morbidity1

Obesity

Overweight

Visceraladiposity

Insulinresistance

Fluid

retention

Hypertension

Dyslipidaemia

Inflammation

Chronickidneydisease

Chronicliverdisease

Type2diabetes

Heartfailure

Atrialfibrillation

Atherosclerotic

cardiovascular

disease

Sleepapnoea

82m

Overweight

BMI:25-302

39%

ofoverweight

populationhas≥1co-morbidity1

36m

Multi-organeffects

Theweightmanagement

landscapecontinuestoevolve

Incretins

foundationalefficacy

withsuperiorweightloss

Oralsandcombinations

targetingadditionalefficacyandimprovedconvenience

Beyondincretins

targetingsustainedweightlosswhilepreservingleanbody

mass;improvedtolerability

2ndgen.

3rdgen.

1stgen.

LandscapeandStrategy

Goingbeyondobesitytoimprovequalityof

weightlossandmanagekeyco-morbidities

Population(millions)

63%ofpatientsdiagnosedwithobesityalsosufferfromoneormorecomorbidities2

overweightobesity

>50%ofglobalpopulation

willsufferfrom

overweightor988

63%

obesityby203511,6152,091

1,914

82mpatientshave≥1co-morbidity

20202035

Keyco-morbidities*

$4.32tn

Est.cost($trillions)

Obesityestimatedtocosttheeconomy

3%ofglobalGDP1

MASH/MASLD

T2DHFCKDDyslipidaemia

$1.96tn

38m14m37m51m10m

20202035

1.WorldObesityAtlas2023.Excludeschildrenunder5years.2.TriNetX(USEHRdata),November2020andOptumclaimdata.ObesitydefinedasICD10codesE66.0,E66.1,E66.2,E66.8,E66.9;T2DdefinedbyICD10codeE11;CKDdefinedbyeGFRlevelsbetween15and75(CKDstages2-4);heartfailuredefinedbyICD10code150;NASH/NAFLDdefinedbyICD10codesK75.81andK76.0;dyslipidaemiadefinedbyLDL>70.*%addsuptomorethan82.2masmanypatientshaveseveralco-morbidities.

8GDP=grossdomesticproduct;est.=estimated;T2D=type2diabetes;HF=heartfailure;CKD=chronickidneydisease;MASH=metabolicdysfunction-associatedsteatohepatitis;MASLD=metabolicdysfunction-associatedsteatoticliverdisease.

LandscapeandStrategy

Deliveringdurableweightloss,addressing

cardiometabolicriskandprotectingorgans

Obesity(±othersevereco-morbidities)

Overweight

(+organ

protection)

T2D

(±obesity/

overweight+

organprotection)

AZD5004

oGLP-1RA

AZD5004

oGLP-1RA

AZD5004

oGLP-1RA

Potentialdualmechanismcombinations

Potentialdualmechanismcombinations

AZD6234

LAamylin

dapagliflozin

SGLT2i

dapagliflozin

SGLT2i

AZD5004

oGLP-1

AZD5004

oGLP-1

AZD9550

GLP-1RA/glucagon

AZD0780

oPCSK9

AZD5004

oGLP-1

AZD5004

oGLP-1

AZD0780

Potentialtriplemechanismcombination

oPCSK9

AZD9550

GLP-1/glucagon

AZD6234

LAamylin

oGLP1RA=oralglucagon-likepeptide-1receptoragonist;LA=long-acting;SGLT2i=sodium-glucosecotransporter-2inhibitor;oPCSK9=oralproproteinconvertasesubtilisin/kexintype9.

9Collaborationpartner:Eccogene(AZD5004).

LandscapeandStrategy

ThreehighpotentialassetsprogressingtoPhaseIIb

山$5bn+*

oGLP-1

long-actingamylin

AZD6234+AZD9550

AZD5004

AZD6234

molecule

?Strongtargetengagement

?Oralonce-dailydosing

?Combinationsacrossobesity,weightmanagement,andtype2diabetes

Small

?

amylinagonist

?Once-weeklys.c.dosing

?Leanmass-sparingweightloss

?Replacementtherapyoptionforincretinintolerance

Selective

?

mechanism

?Once-weeklys.c.dosing

?Maximumweightlosswithouttolerabilitycompromise

?Organprotection

Triple

?

TwoPhaseIIbtrialsinitiated

PhaseIIbtrialinitiated

PhaseIIbtrial

planningunderway

long-actingamylin+GLP-1/glucagon

*PeakYearRevenuepotential,non-riskadjustedforfranchise;includesseveralmedicineswithmulti-blockbusterpotential.AcronymdefinitionscanbefoundinGlossary.oGLP-1=oralglucagon-likepeptide-1;s.c.=subcutaneous.

10Collaborationpartner:Eccogene(AZD5004).

AZD5004

OralGLP-1RA

ElisabethBj?rk

SVP,LATECVRM

11

AZD5004|oGLP-1

AZD5004isapotentoralGLP-1smallmolecule

Noadverseeffectsinpreclinical9-monthtrial1anddose-dependentdifferenceinbodyweightgainvs.controls

(10mg/kg/day)–control

Mean%changeinbodyweight

inNHPs(95%CIs)

Female

Male

10

0

-10

-20

-30

-40

10

0

-10

-20

-30

-40

(50mg/kg/day)–control

-11.4%

-36.5%

(30mg/kg/day)–control

-8.5%

-31.3%

-10.3%

-15.8%

050100150200250050100150200250050100150200250

Daysofdosing

Intravenousglucosetolerancetest1confirmstarget

engagementacrossrangeofdosestestedinPhaseItrial

60000

InsulinAUC

(changefrombaselineμU*min/mL)

50000

40000

30000

20000

10000

0

-10000

25mg*

45mg*

1mg*3mg*

18mg*

8mg*

0.001

1

0.010.1

Exposure(nM)

*humanequivalentdoses

ConductedinNHPs.NHP=non-humanprimate;AUC=areaundercurve.Haggag,A.Non-clinicalandfirst-in-humancharacterizationofECC5004/AZD5004,anovelonce-daily,oralsmallmoleculeGLP-1receptoragonist.DOI:10.1111/dom.16047.

12Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

PhaseIfirst-in-humanSAD/MADtrialconductedin

controlledin-patientsettingwithfastingrequirements

Controlledin-patientsettingincluded14-hourfastingwindowand1,800averagedailycaloricintake

Primaryendpoint:

safetyandtolerability

Part1-SADinhealthyparticipants

CohortA2(N=8;A/P=6/2)

P2

100mg

P3

200mg

P1

50mg

P4

300mg

CohortA1(N=8;A/P=6/2)

P3

10mg

P4

25mg

P2

4mg

P1

1mg

Secondaryendpoint:

pharmacokinetics

Part2-MADinpatientswithT2D

Cohort3

(N=12;A/P=9/3)

Cohort2

(N=12;A/P=9/3)

Cohort1

(N=12;A/P=9/3)

Cohort4

(N=12;A/P=9/3)

30mg|QD28days

notitration

50mg|QD28days

withtitration

10mg|QD28days

notitration

5mg|QD28days

notitration

10mg|Days1-7

ExploratoryPDendpoints:

MADCohort4:titrationschedule

25mg|Days8-14

glucose(OGTT,MMTT)andbodyweight(MAD)

50mg|Days15-28

NCT05654831

NB:DoserangeforMADdisclosedonCT.govwas5-150mg;50mgwasmaxdosestudiedas10-30mgwaspredictedtobetherapeuticdoserangeforT2Dfromemergingdata.

SAD=single-ascendingdose;MAD=multiple-ascendingdose;a=active,p=placebo,PD=pharmacodynamic;OGTT=oralglucosetolerancetest;MMTT=mixed-mealtolerancetest;T2D=type2diabetes.

13Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

SAD/MADPKsupportspotentialforimproved

tolerabilityprofileandonce-dailydosing

FlatSADPKprofileMADPKconsistentwithSADPK

WeightnormalisedAZD5004

concentration(ng/mL)

AZD5004concentration(ng/mL)

MAD-5mg

Day28

Day2-27

Day1

4mg

1mg

40

30

20

10

0

3

10

10

10

10

10

2

1

MAD-10mg

150

100

0

-

50

0

1

MAD-30mg

600

400

200

3000

2000

1000

3

10

10

10

10

10

2

0

1

MAD-50mg

0

-

1

10mg

25mg

200mg

300mg

50mg

100mg

0

01020304050010203040500102030405001020304050

0612182406121824061218

24

oabovelowerlimitofquantification

Timesincefirstdose(hours)

5mg

10mg

30mg

25mg

50mg

Dose(mg)

MAD=multipleascendingdose;PK=pharmacokinetic;SAD=singleascendingdose;QD=once-daily.

14Haggag,A.,et.al.Safety,TolerabilityandPharmacokineticsofAZD/ECC5004,anOralSmallMoleculeGLP-1ReceptorAgonist.PresentedatObesityWeek2024.DOI:10.1111/dom.16047.Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

AZD5004maybeadministeredwithorwithoutfood

Nosignificantfoodeffectobservedinfoodeffecttrial

AZD5004concentration(ng/mL)

1000

500

250

100

Half-lifeat50mg:

20.7hfed

21.2hfasted

10

1

0

Fed

24

Fasted

96

120

4872

Time(hours)

SAD=singleascendingdose;PK=pharmacokinetic.Haggag,A.et.al.AZD5004/ECC5004,aSmallMoleculeGLP-1ReceptorAgonistMayBeAdministeredOnceDailyUnderFed/FastedConditions.PresentedatObesityWeek2024.

15Collaborationpartner:Eccogene(AZD5004).NCT06268145.

AZD5004|oGLP-1

Doses50mgorbelowwell-tolerated

inhealthyvolunteerSADtrial

CohortA1CohortA2

AZD5004

100mg

N=6

AZD5004

300mg

N=6

AZD5004

200mg

N=6

PlaceboN=8

TotalN=9

PlaceboN=8

2(25)

0

TotalN=9

4(44)

2(22)

AZD500410mg

N=6

AZD500425mg

N=6

Variables,n(%)TEAEs

Drug-related

AZD500450mg

N=6

4(67)

2(33)

1(17)

0

3(50)

1(17)

0

1(17)

0

6(100)

6(100)

6(100)

6(100)

6(100)

5(83)

1(13)

0

9(100)

9(100)

0

0

Leadingtostudydiscontinuation

1(11)

0

2(22)

1(11)

0

1(17)

0

1(17)

0

0

1(11)

0

9(100)8(89)

0

0

0

0

0

0

0

0

0

0

0

0

0

4(67)

4(67)

0

0

0

0

0

0

0

0

5(84)

5(83)

0

0

0

5(83)

3(50)

0

TEAEs

Drug-relatedTEAEsNausea

VomitingDiarrhoea

SAD=singleascendingdose;TEAE=treatmentemergentadverseevent.DiscontinuationsduetooralcandidiasisandCOVID-19infection.Haggag,A.,et.al.Safety,TolerabilityandPharmacokineticsofAZD/ECC5004,anOralSmallMoleculeGLP-1

16ReceptorAgonist.PresentedatObesityWeek2024.DOI:10.1111/dom.16047.Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

Tolerabilitysupportslimitedneedfor

Total

N=51

AZD50045mg

N=9

AZD500410mg

N=9

AZD500430mg

N=10

PlaceboN=13

AZD5004

50mg(uptitrated)

N=10

9(90)

9(90)

6(60)2(20)1(10)

1(10)1(10)

7(70)

6(60)2(20)2(20)

2(20)

Variables,n(%)TEAEs

Drug-relatedGrade1

Grade2

Drug-relatedTEAEwithGrade≥31Leadingtostudydiscontinuation

TEAEs

Drug-relatedTEAEs

Gastrointestinaldisorders

Nausea

ConstipationDiarrhoea

Vomiting

37(73)

33(65)

32(63)

4(8)

1(2)

2(4)2(4)

29(57)

15(29)14(28)10(20)

3(6)

7(78)

4(44)

7(78)

0

0

10(100)

10(100)

10(100)0

0

8(62)

8(62)

7(54)1(8)

0

3(33)

2(22)

2(22)1(11)

0

1(10)1(10)

9(90)

6(60)7(70)2(20)

1(10)

0

0

3(33)

1(11)

0

3(33)

0

0

0

7(54)

1(8)3(23)3(23)

0

0

0

3(33)

1(11)2(22)

0

0

titrationinMADtrial

1.Grade3TEAEsincludeAZD500450mg(uptitrated):1(10.0),Total:1(2.0).NoGrade4TEAEs.MAD=multipleascendingdose;E=numberofevents;TEAE=treatment-emergentadverseevent.Twodrug-relatedTEAEsleadingtodiscontinuation:eventtermsQTcprolongation,transientlyasymptomaticelevatedliverenzymes.Haggag,A.,et.al.Safety,TolerabilityandPharmacokineticsofAZD/ECC5004,anOralSmallMoleculeGLP-1ReceptorAgonist.PresentedatObesityWeek2024.DOI:10.1111/dom.16047.

17Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

ExploratoryPDdatafromSADtrialconfirm

targetengagementofGLP-1R

Reductioninglucoseinhealthyvolunteersduringoralglucosetolerancetestfromdoses≥4mg

GlucoseAUC

percentchangefromD-1toD1

GLP-1R=glucagon-likepeptide-1receptor;AUC=areaundercurve.

18Haggag,A.,et.al.Safety,TolerabilityandPharmacokineticsofAZD/ECC5004,anOralSmallMoleculeGLP-1ReceptorAgonist.PresentedatObesityWeek2024.DOI:10.1111/dom.16047.Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

Reductioninglucoseandbodyweightobserved

inMADT2Dtrialat50mg

Fastingglucose

GlucoseAUC(MMMT)Bodyweight

0

%changefromBLinMMTTglucoseAUC

0

0

ChangefromBLinfastingglucose

atDay28,mg/dL(Mean±SD)

%changeinbodyweight

-2

atDay28(Mean±SD)

-50

frombaseline

-20

-4

-100

-40

-6

-8

-60

-150

0102030

Days

BL:189.7mg/dL

BLBMI:31.1kg/m2|BLBW:81.3kg

-76.6mg/dL

-51.7%

-5.8%

AZD500450mg(N=10)Placebo(N=3)

Titration:10mg7days,25mg7days,50mg14days.MAD=multipleascendingdose;T2D=type2diabetes;BL=baseline;BW=bodyweight;MMTT=mixed-mealtolerancetest;AUC=areaundercurve.

19Haggag,A.,et.al.Safety,TolerabilityandPharmacokineticsofAZD/ECC5004,anOralSmallMoleculeGLP-1ReceptorAgonist.PresentedatObesityWeek2024.DOI:10.1111/dom.16047.Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

Dose-dependentreductioninglucoseandbodyweight

observedinMADT2Dtrial

Bodyweight

FastingglucoseGlucoseAUC(MMMT)

Changefrombaselineinfasting

plasmaglucoseatDay28(mg/dL)

0

-38.5mg/dL

-49.6mg/dL

-50

-68.6mg/dL

-76.6mg/dL

-100

-150

07142128

Trialday

50mgAZD500450mgplacebo

10mgAZD500410mgplacebo

5mgAZD50045mgplacebo

30mgAZD500430mgplacebo

GlucoseMMTTAUC0-4

(hxmg/dL)

Changefrombaselineinbody

weightatDay28(%)

1500

1200

900

-26.2%

-39.2%

-28.6%

600

-51.7%

0

-2.5

-3.6%

-3.3%

-4.9%

-5.0

-5.8%

-7.5

-10.0

07142128

Trialday

-11428

Trialday

50mgAZD500450mgplacebo

5mgAZD50045mgplacebo

10mgAZD500410mgplacebo

30mgAZD500430mgplacebo

5mgAZD50045mgplacebo

10mgAZD500410mgplacebo

30mgAZD500430mgplacebo

50mgAZD500450mgplacebo

Dashedgreylinesrepresentplacebo.ChangesinfastingglucoseinAZD5004arms:meanbaselinefastingglucose179mg/dL.MAD=multipleascendingdose;T2D=type2diabetes;MMTT=mixed-mealtolerancetest;AUC=areaundercurve.

20Haggag,A.,et.al.Non-clinicalandfirst-in-humancharacterizationofECC5004/AZD5004,anovelonce-daily,oralsmallmoleculeGLP-1receptoragonist.DOI:10.1111/dom.16047.Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

AZD5004PhaseIdatasupportsinitiationofPhaseIItrials

Provenmechanismandpotency

-EvidenceofGLP-1receptortargetengagement

-Promisingpotency

-FlatPKprofile

-Smallmolecule

Encouragingsafety

profileatrangeofdoses

-Noseriousadverseevents

-Favourabletolerabilityprofilewithadditionaldosing

flexibility

Favourablerouteofadministration

-Once-dailyoraladministration

-Suitablefororalcombinations

-Maybetakenwithorwithoutfood

RapidlyprogressingintoPhaseIIbwithVISTAobesityandSOLSTICEtype2diabetestrialsenrolling

GLP-1=glucagon-likepeptide-1;PK=pharmacokinetic.

21Collaborationpartner:Eccogene(AZD5004).

22Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

PhaseIIbVISTAdesignedtoevaluate

bodyweightreduction

Follow-up

VISTA

NCT06579092|Randomised,double-blind,placebo-

Patient

population:

Arm1|AZD5004|DoseX

―≥18yearsold

Arm2|AZD5004|DoseX

controlleddosefindingtrial

―BMI≥30kg/m2orBMI

Arm3|AZD5004|DoseX

Screening

≥27kg/m2andoneobesity-

Arm4|AZD5004|DoseX

relatedcondition―Weightstable

Arm5|AZD5004|DoseX

―Non-diabetic

N=304

placebo

Arm6

matched

Primaryendpoints:

26weeks–primaryanalysis

36weeks

10weeks

percentchangeinbodyweight

vs.baselineat26weeks;proportionofparticipantswithweightloss≥5%frombaselineweightat26weeks

魚

BMI=bodymassindex.

23Collaborationpartner:Eccogene(AZD5004).

AZD5004|oGLP-1

PhaseIIbSOLSTICEdesignedtoevaluate

effectonglycaemiccontrol

SOLSTICE

NCT06579105|Randomised,double-blind,placebo-

controlleddosefindingtrial

population:

Follow-up

Patient

Arm1|AZD5004|DoseX

≥18yearsold

HbA1c≥7.0%and≤10.5%BMI≥23kg/m2

T2Dbackground

―

Arm2|AZD5004|DoseX

―

Arm3|AZD5004|DoseX

―

Screening

R

―

Arm4|AZD5004|DoseX

therapy:dietandexerciseand/orstabledoseof

metforminorSGLT2i

Primaryendpoint:

Arm5|AZD5004|DoseX

N=384

Arm6|AZD5004|DoseX

Arm7|oralsemaglutide|14mg

matched

placebo

Arm8

26weeks

changeinHbA1Cfrombaselineat26weeks

魚

T2D=type2diabetes;HbA1c=haemoglobinA1c;BMI=bodymassindex;SGLT2i=sodium-glucosecotransporter-2inhibitor.

AZD5004|oGLP-1

Opportunityforadditionalcardiovascularbenefit

throughsmallmoleculecombinations

Dyslipidaemia

+AZD0780

(oPCSK9)

TYPE2

Potentialtofurther

reducehigh-risk

cardiovascular

disease

CKD

+dapagliflozin

(oSGLT2i)

HF

+dapagliflozin

(oSGLT2i)

Potentialtodeliver

renaloutcome

benefits

Potentialtodeliver

cardiovascular

outcomebenefits

SuperiorHbA1c

controland

weightreduction

+dapagliflozin

(oSGLT2i)

T2DM

AZD5004

oGLP-1RA

oGLP-1RA=oralglucagon-likepeptide-1receptoragonist;T2DM=type2diabetesmellitus;oSGLT2=oralsodium-glucosecotransporter-2;HbA1c=haemoglobinA1c;CKD=chronickidneydisease;HF=heartfailure;oPCSK9=oralproprotein

24convertasesubtilisin/kexintype9.Collaborationpartner:Eccogene(AZD5004).

AZD6234

Long-actingamylin

ReginaFritscheDanielson

SVP,EARLYCVRM

25

AZD6234|LAamylin

Amylinagonismpromotesweightlossbyreducing

fatmasswhileretainingleanmassinpreclinicalstudy

Dose-dependentdecreasedrivenbyreductioninfatmasswithleanmasspreservedinobeseratstreatedwithAZD6234

ChangeinmassfromDay0toDay152(g)

15-dayonce-dailytreatment1

N=8pergroup

2

%changeinbodyweight

normalisedtovehicle

40

20

0

Fatmass(g)

Freefatmass(g)

*

********

****

****

-2

-4

-6

-8

-10

-12

10

30

0

******

20

****

-10

****

********

10

-20

-30

0

*

051015

Days

VehicleAZD62343nmol/kgAZD623410nmol/kgAZD623420nmol/kgsemaglutide3nmol/kgsemaglutide10nmol/kg

1.***p<0.001,****p<0.0001;two-wayANOVA,Dunnett’smultiplecomparisontest.2.*p<0.05,****p<0.0001;one-wayANOVA,turkeymultiplecomparisontest.s.c.=subcutaneous.ANOVA=analysisofvariance.Hornigold,D.et.al.CharacterisationofAZD6234,a

26novelamylinreceptorselectiveagonistpeptide,inrodentmodelsofweightlossandaversion.PresentedatEASD2024.

AZD6234|LAamylin

PhaseISADdemonstratedefficacywithpromisingtolerability

Exposureresponsefornausea/vomiting

BodyweightchangeaftersingledoseofAZD6234

Meanbodyweightchange

frombaseline(%)

Cmax(mg/L)

2.7mgdeemedmaximum

tolerablesingledose(mildnausea/vomiting)

0.4

0.3

0.2

0.1

0

Followingsingle2.7mgdose,ameanweightlossof1.7%and

3.8%wasseenintheglobalandJapancohortsrespectively

Mild

nausea1

Decreasedappetite

Trialday

MildModerateSevere

None

vomiting1vomiting1vomiting1

i.v.globals.c.global

0.3mg0.9mg

1.5mg2.7mg

4.2mg

s.c.Japanplacebo

s.c.Japan0.3mg

0.9mg1.5mg

2.7mg4.2mg

△

i.v.globals.c.global

1.Nauseaandvomitingseveritycalcification.Mild:awarenessofsignorsymptom,buteasilytolerated.Moderate:discomfortsufficienttocauseinterferencewithnormalactivities.Severe:incapacitating,withina