医学交流课件：Respiratory Spectrum Present and Future of Respiratory Treatments in AZ

RespiratorySpectrum:PresentandFutureofRespiratoryTreatmentsinAZ1审批编号：435730.022有效期至：2016/05/282Advancingrespiratorymedicinetoimprovepatients’livesacrossthreedimensionsInhaledtherapiesTargetedtherapiesDiseasemanagementAZ’svisionistobecomeanindustryleaderininnovativeinhaledandtargetedtherapiesforAsthmaandCOPD3Respiratory:Expandingbreadth&depthofpatientofferingCurrentfranchiseBiologicsExpandedpresenceTudorza/EkliraDuaklirDalirespBeVespi/PT003(LAMA/LABA)COPDNEW:FDAapprovedBeVespiinApril2016!PT010(LAMA/LABA/ICS)COPD/Asthma

NEW:

Firstpatientdosedin

PhaseIIIprogramme2018regulatorysubmissionTralokinumab(IL-13)SevereasthmaNEW:

CDxdealwithAbbott

2018regulatory

submissionBenralizumab(IL5Rα)severeasthma,COPDNEW:

AchievedprimaryendpointintwopivotalPhaseIIIregistrationtrials(SIROCCOandCALIMA)PipelineProductsInhaledFurtherexpansionPotentiallydisease-modifyingStronggrowthinEmergingMarketsNewgrowthopportunitiesinestablishedmarkets

thattransitiontoEmergingMarketsovertimeAbediterol(LABA)asthma/COPDPhaseIIAZD8999(MABA)COPD,PhaseII45MEDI9929TSLPAZD1419

iTLR9BenralizumabIL5RαTralokinumabIL13AZD9412InhaledIFNβPearl/PT010LAMA/LABA/ICSPhaseILargemoleculeSmallmoleculePhaseIILargemoleculeSmallmoleculePhaseIII/RegistrationLargemoleculeSmallmoleculeMEDI7836IL-13NGAZD7624

ip38Pearl/PT010LAMA/LABA/ICSBenralizumabIL5RaPT003LAMA/LABAAZD9412InhaledIFNβAZD7594iSGRMAZD8871MABAAbediterolLABAPearl/PT009ICS/LABAAZD7986DPP1AZD8999MABAApproved/MarketedeCOPDASTHMAOurpipelineandportfolioreflectourcommitmentAZD7594iSGRM6PT003(BeVespi)

(glycopyrronium/formoterol)istheonlyLAMA/LABAcombinationproductinlate-stagedevelopmentinaHFAMDIdosageformulationforthetreatmentofpatientswithCOPD.ChinaLeadingPIisProf.ZhongNanshan.

ThefirstsubjectwasrecruitedinApril2016PT010

(glycopyrronium/formoterol/budesonide)isatriplecombinationofLAMA/LABA/ICSinaHFAMDIdosageformulationforthetreatmentofpatientswithCOPD.Therearetwostudiesplannedwithprimaryendpointaslungfunctionorexacerbation.Bothstudiesplantostartin2016Q3.ChinaLeadingPIisProf.WangChen.PT003(BeVespi)andPT010Overview

PatentedCo-suspensionTechnology(CST)HFAsuspensiondropletDrugcrystalsco-suspendedwithporousparticles药物结晶合作与悬浮颗粒的多孔7Benralizumabisapotentanti-IL5RantibodywhichisinPhaseIIIdevelopmentforsevereasthmaandCOPDAsthma:AchievedprimaryendpointintwopivotalPhaseIIIregistrationtrials(SIROCCOandCALIMA)DifferentiatedprofileTargetingeosinophilsandbasophilswithinasthmasubgroupsDiffersfromotheragentsindevelopmentthattargetstheIL-5ReceptorRapidonsetofactionImprovementinlungfunctionandasthmacontrolConvenientpre-filledsyringe;everyfourweekdosingorpotentiallyeveryeightweekdosingEngineeredforgreateraffinityfortheFcreceptoroneffectorcellsthroughafucosylation.Afucosylationleadstoefficienteosinophilandbasophildepletion,throughenhancedantibodydependentcell-mediatedcytotoxicity(ADCC)Source:M.Castroetal.,LancetRespiratoryMedicine,2014TralokinumabisafullhumanIgG4monoclonalantibodytargetingIL-13IL-13blockadehasbeenshowntoreducethedownstreamsignalsthatmaymediatethecentralpathologicalfeaturesofpersistentasthma:SmoothmusclecontractionandproliferationTh2-typeinflammationIgEproductionMucushypersecretionCollagensynthesisanddepositionPossiblebiomarkersforIL-13arePeriostinandDPP4Proposedindication:Adultsandadolescentswithinadequatelycontrolledasthmaonmedium-high-doseinhaledcorticosteroid/longactingβ2agonist(ICS/LABA)79AZD9412(IFN-β1a)inhaledbiologic,firston-demandtreatmenttopreventasthmaexacerbationsViralinfectioninoneofthemostfrequentcausesofasthmaandCOPDexacerbationsInterferonbeta(IFN-β)producedasnaturalresponse.InhaledAZD9412mayboostsuppressedimmuneresponsePh2INEXASstarted10AZD1419(iTLR-9agonist)–towardsdiseasemodificationinasthmaAnexaggeratedimmuneType2responseisacommonunderlyingfactorinasthma,thisispartofthehygienetheorywithTH1toTH2cellimbalanceAZD1419attemptstocorrecttheimbalancedimmuneresponseRebalancingtheimmunesystem,aimtoachievedisease-freeperiodsPhaseIIbplannedfor2016

MEDI3506MEDI3506(anti-IL-33),aNMEapprovedasaCandidate(CD):potentialmultipleindicationsincludingCOPDAnupstreaminitiatorthatcontrolstheresponsetoairwayinsultMechanismofaction:anti-IL-33MEDI3506targetsthetopoftheinflammatorycascadeandinhibitmultiplemechanismsinvolvedinairwaysdiseasePotentialtotargetabroadpatientpopulation11LAMA/LABAICS/LABA/LAMAICS/LABA/LAMAplus:PDE-4;IL-5,ABsEmergingParadigmPatientswith

bronchoconstrictionandinflammation*Somepatientsneed

addedprotectionagainstexacerbationsPatientswithbronchoconstrictionLAMAICS/LABAICS/LABA/LAMAplus:ABs,OCS

Openairways,improvelungfunction,symptomsandactivityOpenairwaysanddecreaseinflammation&exacerbationsOpenairwaysanddecreaseinflammationandexacerbationsandprovideadditionalriskreduction*Medicalhistory(exacer