2023 JPM 第41届摩根大通医疗健康年会 -Sutro

NON-CONFIDENTIALNON-CONFIDENTIAL40thAnnualJ.P.MorganHealthcareConferenceJanuary2022ryonon22NON-CONFIDENTIALDrugDiscoveryPlatformEnablesthePotentialforBest-in-ClassMoleculesPrecisenoveldesigntoenhanceefficacyandsafetyacrossmultiplemodalitiesandtargetsCytokineDerivativeConjugatedAntibodyBispecificAntibodyProdrugCytokineDerivativeADCorISACiADCBispecificADCImmuneCellEngagerTumoTumorSelectiveMaskTumoTumorAntigenTumoTumorAntigenDuDualTumorAntigensTumorTumororStromalAntigenImmuneImmuneCellEngagercytokineReleasablemaskProdrugcytokinetargetingfunctionalcytokinetotumorADC:targetingnovelpayloadsSite-specificdualdrugconjugatewithcomplementarymodalities(TMEmodulator+/-immunemodulator)Enhancedtumortargetingofcytotoxicpayloads Improvedspecificityforoptimizedtherapeuticwindow 33NON-CONFIDENTIALRobustPipelinethroughWholly-OwnedandPartneredProgramsFourproductcandidatesadvancingintheclinicandlate-stagediscoveryprogramsicalFastTrackDesignationOvarianCancerOvarianCancerFolRαADCSTRO-002(FolRαADCSTRO-002(GreaterChina(GreaterChina)Antibody-DrugNSCLC/Non-GynAntibody-DrugConjugateSTRO-001CDConjugateSTRO-001CD74ADC(GreaterChina)OrphanDrugDesignationOrphanDrugDesignationMultipleMyelomaMultipleMyelomaCC-99712BCMACC-99712BCMAADCROR1,TissueFactorMUC1-EGFRADC5T4-CD3TCECytokinetargetNILIL(GSIcombo)DiscoveryDiscoveryM1231PreclinicalNotDisclosedDiscoveryVAX-24BispecificADCT-CellEngagerBispecificADCT-CellEngagerCytokineDerivativeVaccine2Molecules2MoleculesCancerSolidTumorsINDclearanceInvasivePneumococcalINDclearance(1)EMDSeronoisthebiopharmaceuticalbusinessofMerckKGaA,DarmstadtGermanyintheUS(2)CytokineDerivativeprogramwithMerckincludestwomoleculesderivedfromoneundisclosedtarget44NON-CONFIDENTIALAchievementsandMilestonesClinicaldatareadoutsandpartnershipsprovidemultiple2022valuedriversforSutro ✓GreaterChinadealwithTasly(Dec.2021) ✓Ovariancancerdose-expansioninterimdata(Jan.2022)Dose-expansiondatawithdurabilityatascientificmeeting(2H2022)EOP1/2meeting(1H2022)Initiatepivotaltrialinovariancancer(YE2022) ✓Firstpatientdosedinendometrialcancer(Nov.2021)Firstpatientdosedinbevacizumabcombinationtrial(1Q2022)SupportTaslyforinitiationofclinicaldevelopmentactivitiesinGreaterChina(2022)InitiateclinicaltrialforNSCLCandothernon-gynecologicsolidtumors(2H2022) ✓GreaterChinadealwithBioNova(Oct.2021)SupportBioNovaforinitiationofclinicaldevelopmentactivitiesinGreaterChina(2022)DetermineRP2Dthroughdoseescalation(2022)ellFreeManufacturingforPartneredPrograms•Providemanufacturingmaterials&supportforCC-99712,BCMAADCinclinicaldevelopment(BMS)•Manufactureinitialproductforpotentialclinicaldevelopmentofcytokinederivative(Merck)•ManufactureM1231product,MUC1-EGFRADCinclinicaldevelopment(EMDSerono)•Supplycell-freeextract&reagentstoVaxcyteforVAX-24,INDclearanceannounced•SupporttechtransfersandenableBMSandEMDSeronotomanufacturefromSutro’scell-freeextract55NON-CONFIDENTIALNON-CONFIDENTIALNON-CONFIDENTIALttumorresponsesbroadrangeoftargetantigenlevelsFolRFolRppAMF2YY1803ProteaseProtease-cleavablelinkerderivativewarheadHemiasterlin-STROSTRO-002isahomogeneousantibodydrugconjugate(ADC)withadrug-antibodyratio(DAR)of4,targetingfolate-receptoralpha(FolRα)FolRαisoverexpressedincertaincancersincludingovariancancerandendometrialcancerPreciselypositionednon-naturalaminoacids,p-azidomethyl-L-phenylalanine(pAMF),atpositionsY180andF404ontheheavychainStableprotease-cleavablelinkers,withrapidclearanceWarheadishemiasterlin-derivative1withpotentiallydualmechanismagainstthetumor–tubulin-inhibitorcytotoxin,lesssensitivetoP-gptransportandinducesimmunogenicresponseuponcelldeath2oftoxiccataboliteafterreleaseandcellkilling1Sutro-proprietarytubulin-targeting3-aminophenolhemiasterlinwarhead,SC2092BasedonSTRO-002pre-clinicalmodelsshowingimmunestimulationatsiteoftumoruponcelldeath77NON-CONFIDENTIALhort•~50%1-2linesoftherapy,hort•~50%1-2linesoftherapy,~50%3linesoftherapyacrossallpatients,aswellasbothdosecohorts•Majority(~81%)wereplatinumresistant;platinumsensitive(~19%)•Otherpriortherapies:substantialbevacizumab(63%)andPARPinhibitor(65%)usedataon43patientspresentedinJan.2022Two-partdesigntoexploresafety,anti-tumoractivity,dosing,andFolRαenrichmentstrategyCohort•Heavilypre-treatedovariancancerpatientswith6medianlinesof•Heavilypre-treatedovariancancerpatientswith6medianlinesofpriortherapies•100%withpriorplatinumregimens,46%with≥3priorplatinum-containingregimens•Otherpriortherapies:substantialbevacizumab(82%),PARPinhibitors(59%),andcheckpointinhibitors(21%)useionlevelstissuerequireduponProtocolalysismensorplatinumsensitivewithinumregimensprogressingafterpriorregimensomizedatmgkgandmgkgstartingdosevoluntaryandsamplesreceivedfrom<50%ofpatientsInclusiveofallpriorlinesoftherapy9doseescalationlevels(0.5-6.4mg/kg)–maximumssnotrequiredProphylacticcorticosteroideyedropsnotrequiredBaselineCharacteristicsStatusFPI:JanStatusFPI:Jan202144patientsenrolled,closedtoenrollmentNov.202139patientsenrolled,closedtoenrollmentAug.2020Interimefficacydataon33evaluablepatientsandsafetyNear-Interimefficacydataon33evaluablepatientsandsafety88NON-CONFIDENTIALN=43lsOvarianCancerPatients4.3mg/kgN=23N=43lsOvarianCancerPatients4.3mg/kgN=235.2mg/kgN=20Medianage,years(range)Mediantimesincediagnosis,years(range)(0.9–4.4)(0.7–5.1)(0.7–5.1)NumberofpriorlinesoftherapyMedian3.02.02.0Mean(St.Dev.)2.5(0.95)2.5(1.05)2.5(0.98)PreviousTherapies,n(%)bevacizumab13(57%)14(70%)27(63%)PARPInhibitor15(65%)13(65%)28(65%)PatientsRandomized&DosedSafetyEvaluable(asofNov8,2021)N=43RECISTv1.1OnePost-BaselineScanN=33NoPostBaselineScanInterimdatafordoseexpansionareasofNovember8,2021PatientBaselineCharacteristicsPatientStatusasofNovember8,2021N=44DiscontinueDiscontinuedPriortoReceivingScanore(TPS)>25%N=2599NON-CONFIDENTIALtingDoseQW4.3mg/kg5.2mg/kgDoseResponseDemonstratedtingDoseQW4.3mg/kg5.2mg/kgInterimdatasuggestthat5.2mg/kgstartingdoseleadstohigherresponseratesMaximumChangeinTumorTargetLesions(N=33)PRu*PRuPRu*PRPRPRPRPRu*PRu*PRPRPR2ptshad0%ΔPartialResponseTreatmentongoingasofNov8,2021*PRconfirmedbynextscheduled*scan(afterNov.8,2021)Note:DataasofNov.8,2021.5PRuwereofinterestandfollowedupsubsequenttothedatacutoffdate.4PRconfirmedattheirnextscheduledscanand1wasSD.1010NON-CONFIDENTIAL•47.1%ORR•47.1%ORRinpatientsstartingatthe5.2mg/kgdoselevel•33.3%ORRinallpatients•Interimdatasuggestthat5.2mg/kgstartingdoseleadstohigherresponserates•All4patientswithPRutreatedat5.2mg/kgweresubsequentlyconfirmedatthenextscheduledscan33%ORRrateinall33evaluablepatients,unenrichedforFolRαexpressionStartingDoseBestOverallResponse(BOR)4.3mg/kg5.2mg/kgAllComersEvaluablepatientsN=16N=17N=33PR347PRconfirmedbynextscheduledscanpostNov.8,2021044TotalPR3811ORR(%)33.3%SD10414PD358Note:DataasofNov.8,2021.5PRuwereofinterestandfollowedupsubsequenttothedatacutoffdate.4PRconfirmedattheirnextscheduledscanand1wasSD.1111NON-CONFIDENTIALChangefrombaseline(%)RobustAnti-Changefrombaseline(%)RespondersexperiencedrapidtumorreductionorasteadydeepeningofresponseChangeinSumofDiametersforTargetLesionsOverTime(N=33)StartingDose,Q3W4.3mg/kg5.2mg/kgasofNovasofNov8,202100481216202428323640WeekssincefirsttreatmentNote:DataasofNov.8,2021.1212NON-CONFIDENTIALIndividualpatientstreatedwithSTRO-002EncouragingResponseRatesandPreliminaryDataonDurabilityIndividualpatientstreatedwithSTRO-002Interimdatasuggestinitiatingwith5.2mg/kgfollowedbyadoseadjustmentInitialdatashowpartialresponsesconfirmed&maintainedfollowingdoseadjustmentMedianDurationInitialdatashowpartialresponsesconfirmed&maintainedfollowingdoseadjustmentMedianDurationofResponsehasnotbeenreachedand23of43patientsremainedonstudyatNov.8,2021DatatoinformRP2Dwithfinaldecisionpendingmoredatamaturitymg/kgmg/kggkgTreatmentongoingasofNov8,2021(N=23)+Nopost-baselinescanasofdatacut-off++++++++++3604812162024283236DataasofNov.8,2021.DataasofNov.8,2021.44thpatienthadnotbeendosedbythisdate.1313NON-CONFIDENTIALAxillaryLymphNode BaselineScreeningofTargetLesions–MayAxillaryLymphNode BaselineScreeningofTargetLesions–May17,2021LateralAbdominalWallInter-aortocavalLNExternalIliacLNOngoingPartialResponsewith72%reductionintumorburdenInitialdiagnosis:StageIVovariancancer,Jan20203PriorRegimens:Resistantto1stNeoadjuvant/adjuvantCarbo/Taxol/TaxotereRefractoryto2ndand3rdwithprogressivedisease•Liposomaldoxorubicin•GemcitabineAxillaryAxillaryLymphNodeScansatCycle5TargetLesions–September8,2021LateralAbdominalWallInter-aortocavalLNExternalIliacLN1414NON-CONFIDENTIALTumorProportionScore(TPS)•PercentTumorProportionScore(TPS)•Percentoftumorcellsshowingstainingofanyintensity•Doesnotrequireanalysisofintensitylevelsandeasytoscore•Commonlyusedinclinicalpractice•Establishedreproducibilityacrossdifferentbiomarkers(e.g.,PD-L1)ExploratoryanalysissuggestsTPS>25%correlatedwithhigherresponseORRbyTPSExpressionLevels(TotalSamplesN=33)TPSOverallTPSTPSTPSTPSORR33.3%12.5%40.0%42.1%43.8%NumberofpatientN=33N=8samplesPR(1)11187PotentialMarket100%~30%Size(%)~70%Patientsatthe5.2mg/kgstartingdoseandTPS>25%demonstrated53.8%ORR(n=13)((1)PRclassificationincludesthe4of5patientswhowereconfirmedbytheirnextscheduledscanafterNov.8,2021.Note:DataasofNov.8,2021.15NON-CONFIDENTIALkidneyinjuryEmergingSafetyProfileisManageable–85.5%ofkidneyinjuryNonewsafetysignalswereobserved,includingtheabsenceofkeratopathyAEsSubjectsbyDose4.3mg/Kg(N=23)Grade3Grade4Grade5n(%)n(%)n(%)5.2mg/Kg(N=20)Grade3Grade4Grade5n(%)n(%)n(%)Total(N=43)Grade3Grade4Grade5n(%)n(%)n(%)Subjectsreportingatleast1event13(57)4(17)08(40)8(40)1(5)21(48)12(28)1(2)Neutropenia(1)10(44)4(17)06(30)8(40)5)16(37)12(28)2)FebrileNeutropenia00000Whitebloodcellcountdecreased4(17)4)05)2(10)05(12)3(7)0Anemia4)003(15)004(9)00Arthralgia4(17)000004(9)00Diarrhea2(9)0005)02(5)2)0Plateletcountdecreased2(9)005)003(7)00Thrombocytopenia0002(10)002(8)00Vomiting0002(10)002(8)00Fatigue2(9)000002(8)00Activatedpartialthromboplastintimeprolonged2(9)000002(8)00Hyponatremia2(9)000002(8)00Neuralgia2(9)000002(8)00Acute0002(10)002(8)00AsymptomaticAsymptomaticneutropeniawastheleadingTEAE,resultingintreatmentdelayordosereduction–Neutropeniaresolvedwith1–Febrileneutropeniaisrare–OneGrade5eventatthe5.2mg/kgdosecohort–OneGrade3eventatthe4.3mg/kgdosecohort–ProtocolwasupdatedtorequiredosereductionforGrade4neutropenia–Dosereductionsamelioratedneutropeniaweekdelay±G-CSF,inthemajorityofcases(1)(1)Neutropeniaincludedthefollowingpreferredterms:neutropenia,febrileneutropenia,andneutrophilcountdecreased.Note:DataasofNov.8,2021.16NON-CONFIDENTIALInterimdatasuggestTPS>25%arecorrelatedwithhigherresponserate,with40%ORR(10/25)InterimdatasuggestTPS>25%arecorrelatedwithhigherresponserate,with40%ORR(10/25)observedinbothdoselevelsBasedonourpatientobservations,webelieveSTRO-002maybeanappropriatetherapyfor~70%ofthesepatientsEmergingdatainformpotentialstartingdoseandenrichmentstrategyyTotalTotalof11confirmedPR(1)outof33RECISTv1.1evaluablepatients33%ORR,acrossallFolRαexpressionlevelsandbothdoselevels447%ORR(8/17)inunenrichedpatientsstartingatthe5.2mg/kgdoselevelInitialdatasuggestresponsesat5.2mg/kgaremaintained,evenwhensubsequentdosereductionsareimplementedPatientsPatientsatthe5.2mg/kgstartingdoseandTPS>25%demonstrated53.8%ORR(7/13)NoNonewsafetysignalswereobserved,includingtheabsenceofkeratopathy85.5%ofTEAEswereGrade1-2NeutropeniawastheleadingTEAE,resultingintreatmentdelayordosereductionProtocolwasupdatedtorequiredosereductionforGrade4neutropenia(1)PRclassificationincludesthe4of5patientswhowereconfirmedbytheirnextscheduledscanafterNov.8,2021andpercentagesonslideincludesuchsubsequentlyconfirmedPRsasappropriate.Note:DataasofNov.8,2021.1717NON-CONFIDENTIALProgressing&ExpandingtheSTRO-002Additionalclinicalstudiesinovarian&endometrial,andnonclinicalworkonothertumortypesComboCombostudywithbevacizumabTrialisopenandenrollingpatientsFPIplannedforearly2022Registration-directedtrialPendingFDAEOP1meetingPrecedentfromsingle-armregistration-directedtrialinadvancedovariancancer4patientsenrolledinUSandnrollmentompletedNovemberpatients,enrollmentsInitialenrollmentplannedfor~15patientsFPIDecember2021CohortisopenandenrollingpatientssketstudydesignwithotherFolRαexpressingcancers1818NON-CONFIDENTIALNON-CONFIDENTIALNON-CONFIDENTIALeses2F404PotentialFirst-in-ClassMoleculeforPatientswithNHLandMM2F404StableCD74targetingADCforhematologicalcancersdesignedtominimizebystandereffectsCDCD7434MaytansinoidwarheadMaytansinoidwarheadlinkergicalarheadsthatatioDAR2020NON-CONFIDENTIALAtotalof21patientshavebeentreatedwithSTRO-001and18patientsAtotalof21patientshavebeentreatedwithSTRO-001and18patientswereevaluableforresponseasofOctober30,2020Doserange0.05-2.5mg/kgandMTDhasnotbeenreached1DLTofgrade3pulmonaryembolismwasobserved(1)Followingpreviouslyannouncedprotocolamendmentrequiringpre-screeningforpatientsatriskforthromboses,noadditionalthromboemboliceventshavebeenobservedDosingfrequencywasmodifiedfromQ2W(28-daycycle)toQ3W(21-daycycle)fordoses≥0.91mg/kgRP2DCohortA3.5mg/kgt2.5mg/kgt1.78mg/kgt1.27mg/kgt0.91mg/kgtOngoingPhase1doseescalationstudywithNHLupdateatASH2020STRO-001-BCM1DoseEscalationStudyNHLCohortUpdateatASH2020RR/Rmultiplemyeloma(N=30)RP2DCohortRP2DCohortBHL(N=30)MTDXmg/kgCohortB,NHLDosingScheduleMTDXmg/kgseescalation4.2mg/4.2mg/kgforNHL&5.0mg/kgfor0.075–0.650.075–0.65mg/kgSingle-dosecohorts1DLTNoneNonePatientstreatedN=6totalN=61DLTNoneNone(1)DLTdisclosedin2019,patientwithbulkylymphadenopathyandconcurrentDVTreceiving0.91mg/kgQ3WAsofOctober2021,thelastreporteddoseslevelswereof5.0mg/kgAsofOctober2021,thelastreporteddoseslevelswereof5.0mg/kginthemultiplemyeloma(MM)cohortand4.2mg/kginthenon-Hodgkin'slymphoma(NHL)cohort.2121NON-CONFIDENTIAL(N=21)BaselineCharacteristicPatientsWith≥1Event,n(N=21)BaselineCharacteristicPatientsWith≥1Event,n(%)Grade1Grade2Grade3Grade4TEAEsbyGrade,Occurringin≥15%Heavilypre-treatedpatientpopulationwith5medianlinesofpriortherapiesAge,median(range),years64.5(21–82)Timefromdiagnosis,median(range),years6.0(1.0–29.8)NHLsubtype,n(%)21(100)DLBCL7(33)Follicularlymphoma7(33)MCL2(10)Marginalzonelymphoma2(10)Burkitt’sLymphomaCompositeDLBCL/FLCompositeDLBCL/CLLNumberofpriortherapies,median(range)5(1-12)Priortherapies,n(%)Autologousstemcelltransplant2(10)UnrelatedallogeneicstemcelltransplantCAR-Ttherapy3(14)Nausea5(23.8)4(19.0)00Fatigue4(19.0)3(14.3)00Chills7(33.3)000Anemia3(14.3)2(9.5)1(4.8)0Headache2(9.5)4(19.0)00Dyspnea1(4.8)3(14.3)1(4.8)0Abdominalpain4(19.0)1(4.8)00Infusionrelatedreaction1(4.8)3(14.3)00Vomiting2(9.5)2(9.5)00Decreasedappetite3(14.3)1(4.8)00Pyrexia3(14.3)1(4.8)00Note:DataasofOctober30,2020fromASH2020.2222NON-CONFIDENTIAL0.075mg/kg0.65,1.27mg/kg1.27,1.78,2.5mg/0.075mg/kg0.65,1.27mg/kg1.27,1.78,2.5mg/kgMultipleCRPRSDDLBCLDLBCLMarginalZoneandFollicular123DoseLevel,mg/kgDurationofTreatmentDosesReceivedDemographicsandDiagnosisoldwithPriorTherapiesPartialresponsesintwoDLBCLpatientswhohadprogressedonCAR-TSD*0.075to0.65mg/kgQ2W0.91mg/kgQ3W1.27mg/kgQ3W1.78mg/kgQ3W2.5mg/kgQ3WContinuingstudytreatment*Patienthadaprolongeddosedelay(cycle2tocycle3)duetoCOVID-19015010020030150100200300StudydayBestBestPatients,STRO-001DoseNHLsubtypeResponsen(1)18patientsareevaluableforresponseasofOctober30,2020ResponsestoSTRO-0010.07582-year-manStageIIIDLBCL,non-GCtypediagnosedin2015••••R-CHOP-R,Rituximab/lenalidomi