CPI-444,anoraladenosineA2Areceptor(A2AR)antagonist,demonstratesclinicalactivityinpatientswith

advancedsolidtumors

LeishaA.Emens1,JohnPowderly2,LawrenceFong3,JoshuaBrody4,PatrickForde1,MatthewHellmann5,BrettHughes6,ShivaaniKummar7,ShereneLoi8 JasonLuke9,Daruka

Mahadevan10,BenMarkman11,IanMcCaffery12,RichardMiller12,andGinnaLaport12

1Johns Hopkins University, Baltimore MD; 2Carolina BioOncology Institute, Charlotte NC; 3University of California, SanFrancisco, San Francisco CA; 4Mount Sinai School of Medicine, New York NY; 5Memorial Sloan Kettering Cancer Center,New York NY; 6Royal Brisbane and Women’s Hospital, Herston, Australia 7Stanford University School of Medicine, PaloAlto CA; 8Peter MacCallum Cancer Center, Melbourne, Australia; 9University of Chicago, Chicago IL; 10University ofArizona, Tucson AZ; 11Monash Health, Victoria, Australia; 12Corvus Pharmaceuticals, Burlingame CA

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Thispresentationcontainsforward-lookingstatements,includingstatementsrelatedtothepotentialsafetyandefficacyofCPI-444,bothasasingleagentandincombinationwithanti-PD-1andanti-PD-L1,theutilityofbiomarkerdatacollectedandthesuitabilityofthedosingregimenselectedfortheCompany’sPhase1/1bclinicaltrialofCPI-444.Allstatementsotherthanstatementsofhistoricalfactcontainedinthispressreleaseareforward-lookingstatements.Thesestatementsoftenincludewordssuchas“believe,”“expect,”“anticipate,”“intend,”“plan,”“estimate,”“seek,”“will,”“may”orsimilarexpressions.Forward-lookingstatementsaresubjecttoanumberofrisksanduncertainties,manyofwhichinvolvefactorsorcircumstancesthatarebeyondtheCompany’scontrol.TheCompany’sactualresultscoulddiffermateriallyfromthosestatedorimpliedinforward-lookingstatementsduetoanumberoffactors,includingbutnot limitedto,risksdetailedintheCompany’sAnnualReportonForm10-KfortheyearendedDecember31,2016,filedwiththeSecuritiesandExchangeCommissiononMarch10,2017,aswellasotherdocumentsthatmaybefiledbytheCompanyfromtimetotimewiththeSecuritiesandExchangeCommission.Inparticular,thefollowingfactors,amongothers,couldcauseresultstodiffermateriallyfromthoseexpressedorimpliedbysuchforward-lookingstatements:theCompany’sabilitytoutilizebiomarkerdata,selectasuitabledosingregimenanddemonstrateevidenceofefficacyandsafetyforCPI-444duringitsPhase1/1b clinicaltrial;theaccuracyoftheCompany’sestimatesrelatingtoitsabilitytoinitiateand/orcompleteclinicaltrials;theresultsofearlyclinicaltrialsmaynotbepredictiveoffutureresults.AlthoughtheCompanybelievesthattheexpectationsreflectedintheforward-lookingstatementsarereasonable,itcannotguaranteethattheeventsandcircumstancesreflectedintheforward-lookingstatementswillbeachievedoroccur,andthetimingofeventsandcircumstancesandactualresultscoulddiffer materiallyfromthoseprojectedintheforward-lookingstatements.Accordingly,youshouldnotplaceunduerelianceontheseforward-lookingstatements.Allsuchstatementsspeakonlyasofthedatemade,andtheCompanyundertakesnoobligationtoupdateorrevisepubliclyanyforward-lookingstatements,whetherasaresultofnewinformation,futureeventsorotherwise.Additionalinformationmaybeavailableinpressreleasesorotherpublicannouncementsandpublicfilingsmadeafterthedateofthispresentation.

ThispresentationconcernsproductsthathavenotyetbeenapprovedformarketingbytheU.S.FoodandDrugAdministration(“FDA”).Norepresentationismadeastotheirsafetyoreffectivenessforthepurposesofwhichtheyarebeinginvestigated.

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ForwardLookingStatements

DisclosureInformation

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Ihavethefollowingfinancialrelationshipstodisclose:Consultantfor:Vaccinex,Celgene,BristolMeyersSquibb,AstraZeneca,Amgen,Syndax,Molecuvax,eTHeRNA,Peregrine, BayerGrant/Researchsupportfrom:Genentech/Roche,EMDSerono,Maxcyte,Merck,AstraZeneca,Aduro,Corvus

Iwilldiscussthefollowingoff-labeluseand/orinvestigationaluse:CPI-444aloneandcombinedwithatezolizumabforadvancedsolidcancers.

StudyfundingprovidedbyCorvusPharmaceuticals.RocheGenentechprovidedatezolizumabandsupportforbiomarkeranalyses

AACR Annual Meeting 2017: Leisha A. Emens

AdenosineSignalingSuppressesImmunityintheTumorMicroenvironment

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• PD-1/PD-L1antibodiesareeffectiveimmunotherapieswithresponserates~20-30%

• Novelagentsthatenhanceresponseorovercomeresistancetoimmunotherapyareahighpriority

• Theadenosinepathwayisapotentialnewimmunotherapytarget

CPI-444:ANovelInhibitoroftheA2ARPathway

• PharmaceuticalProperties– Molecularweight=407Da– A2ARKi=3.5nM– >55-foldselectiveoverA1R,>400-foldA2BRandA3R– Oralbioavailability>50%– Plasmahalflife:~10-14hours

• Singleagentactivityinmultiplepreclinicalmodels*– Synergywithanti-PD-(L)1andanti-CTLA-4antibodiesandothercheckpoint

inhibitors• Well-toleratedinearlytrialswithhealthyvolunteersandADHDpatients

• ThisisthefirstevaluationofsafetyandclinicalactivityofanA2ARantagonistinpatientswithcancer

CPI-444

*SeeAbstract#55985

APhase1/1b,Open-Label,Multicenter,Repeat-Dose,Dose-SelectionStudyofCPI-444asaSingleAgentandinCombinationwithAtezolizumab(atezo)inPatientswithSelectedIncurableCancers

PrimaryObjectives– EvaluatethesafetyofCPI-444aloneandwithatezo– IdentifyarecommendeddoseandscheduleforCPI-444alone

andwithatezo• Safety,PKandPDdata*

– MeasuretheclinicalactivityofCPI-444aloneandwithatezo• ORR,CBRandDOR*

6*PK– pharmacokinetics;PD=pharmacodynamics;ORR=overallresponserate;CBR- clinicalbenefitrate;DOR=durationofresponse

TrialDesign:Step1DoseSelection(Accrualcompleted)

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SelectSingleAgentDose

SelectCombination

Dose**

100mgCPI-444BIDdays1-14/28days*

100mgCPI-444BID28dayscontinuous*

200mgCPI-444dailydays1-14/28days*

50mgCPI-444BIDd1-14/28dayswith840mgatezo every2weeks*

100mgCPI-444BID14or28dayswith840mgatezo every2weeks*

DLTevaluation

DLTevaluation

Eligibility• Selectedincurablecancers:NSCLC,Melanoma,RCC,TNBC,Others

(UBC,CRPC,CRC-MSI+,SCCHN)• 1to5linesofpriortherapy• Stable,treatedbrainmetastasesallowed• Resistant/refractory(R/R)topriorantiPD-1/PDL-1allowed• PD-L1,CD73,A2aRexpressionnotrequiredforenrollment

*1cycle=28days

**SeeAbstract#5593

TrialDesign:Step2CohortExpansionbyDisease(Accrualongoing)

8*Others:CRPC,CRC-MSI,UBC,SCCHN

Randomize

SingleAgentArmExpansion CombinationArmExpansion

NSCLCN=14

MELN=14

RCCN=14

TNBCN=14

Others*N=14

NSCLCN=14

MELN=14

RCCN=14

TNBCN=14

Others*N=14

Potentialexpansionto26and48patients

PatientDemographics/DiseaseCharacteristics*Medianage,years(range) 64(36– 85)

Gender,n(%)FemaleMale

58(51%)55(49%)

ECOGperformancestatus01

47(42%)66(58%)

TNBCNSCLCMELRCCOthers

32 (28%)28(25%)14(12%)14(12%)25 (23%)

Median#ofpriorregimens 2(1–5)

PriorChemotherapyPrioranti-PD1/PD-L1exposure

NaïveResistant/Refractory

VisceralmetastasesLiverBrain

90(80%)

50 (44%)63(56%)102(90%)42(37%)10(9%)

• Enrollment(n=113)• Step1:n=47(33singleagent)• Step2:n=66(26singleagent)

• Heavilypre-treatedwithextensivedisease

• Overhalfwithdiseaseresistant/refractorytoPD-1/PD-L1antibodies

*Datacutoff:Mar20179

Treatment-RelatedAdverseEvents(AE)

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• Mediandurationoftreatment:9weeks(range:upto40+)

• 56%ofpatientsexperiencedatreatment-relatedAE(anygrade)

• Nograde3/4AEswithsingleagentCPI-444

• Immune-relatedAEsseenonlywithcombinationofCPI-444andatezo (n=1foreach):-Pancreatitis(Gr2)-Autoimmunehemolyticanemia(Gr3)-Meningoencephalitis/thrombocytopenia(Gr4)

Adverse Events> 5%Frequency(Gr1/2)SingleAgent Combo

Nausea 14% 13%

Pruritus 10% 9%

Fatigue 5% 7%

AbdominalPain 5% ---

Rash 5% ---

Diarrhea 5% ---

Pyrexia 5% 7%

DecreasedAppetite 5% 7%

Chills 5% ---

OverallPatientOutcomesDiseaseControlRate(CR,PR,SD)inEvaluablePatients

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CPI-444(n=52)

CPI-444/Atezolizumab(n=44)

AllSubjects(n=96)

Allsubjects 20(38%) 17(39%) 37 (38%)

PriorPD-1/PD-L1ExperienceNaïveResistant/Refractory

13/29(45%)7/23(30%)

5/18(28%)12/26(46%)

18/47(38%)19/49(39%)

Disease Histology- NSCLC- MEL- RCC- TNBC- Others

4/14(29%)2/5 (40%)3/5(60%)7/17(41%)4/11(36%)

5/10 (50%)2/6(33%)5/5(100%)3/14(21%)2/9(22%)

9/24(38%)4/11(36%)8/10(80%)10/31(32%)6/20(30%)

• MedianfollowuptimeforDCR:16weeks(range,4-44weeks)• 23/37ofPRandSDpatientsremainonstudy

ClinicalActivity:OverallPatientPopulation*

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• SDsandPRsobservedwithCPI-444aloneandincombinationwithatezo

%Changefro

mBaseline

*PatientswithdiseaseevaluablebyCT,n=70Treatment:SingleAgentCombination

ClinicalActivity:ByDiseaseType

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• TumorregressionobservedinRCC,NSCLC,TNBC,SCCHNandCRC

%Changefro

mBaseline

OTHERTNBCMELNSCLCRCC

ClinicalActivity byPriorPD-(L)1Experience

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• CPI-444hasactivityinpatientsresistant/refractorytoPD-1blockade

• 2PRsand7minorregressionsinPD-1resistant/refractorypatients

• 1PRand4minorregressionsinPD-1naïvepatients

%Changefro

mBaseline

Resistant/RefractoryNaive

DurationofTreatment

15OTHERTNBCMELNSCLCRCC

SingleAgentCPI-444 CPI-444CombinedwithAtezo

TumorRegressioninNivolumab RefractoryLungCancerSingleAgentCPI-444

Pre-treatment 2monthsoftreatment16

• 2priorchemotherapyregimens• Refractorytonivolumab• StartedsingleagentCPI-444

RegressioninNivolumab ResistantLungCancerCombinationCPI-444/Atezolizumab

Pre-treatment 2monthsontreatment17

• 1priorchemotherapy• Respondedtonivolumab,

thenprogressed• StartedCPI-444+atezo

TumorRegressioninNivolumab RefractoryRenalCancerSingleAgentCPI-444

Pre-treatment 3 monthsoftreatment18

• FivepriorregimensincludingTKIsandmTOR inhibitor

• Tumorprogressiononnivolumab

• StartedCPI-444

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SerialBiopsiesofLiverMetastasisfromPD-1RefractoryRCCPatientTreatedwithSingleAgentCPI-444

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Pre-treatment Posttreatment(2months)

InflammatoryInfiltrateinTumor=1%

InflammatoryInfiltrateinTissue=20%

CD8+ intumor=14%

CD8+ intissue>70%;notumorcellsdetectable

InflammationandCD8+ TCellInfiltrationAfterProgressiononPD-1TherapyIncreasedwithSingleAgentCPI-444Therapy

H&E H&E

IHCIHC

SeeAbstract#5593

Conclusions• CPI-444iswelltoleratedasasingleagentandincombinationwithatezo– MostcommonGrade1/2toxicities:nausea,fatigue,pruritus– irAEs ofhemolyticanemia(Gr3),meningoencephalitis(Gr4),andpancreatitis(Gr2)

seenwithcombinationtherapy

• SelecteddoseofCPI-444is100mgbidcontinuous

• Observedclinicalactivity:– Assingleagentandincombinationwithatezo inmultipletumortypesinadvanced

cancerpatients– Inpatientsrefractory/resistanttoPD-1/PD-L1blockade– 23/37patientswithPR/SDremainonstudymedian16weeks

• IncreasedinflammationandCD8+ TcellsinbiopsyobservedinanantiPD(L)-1-experiencedpatientsrespondingtosingleagentCPI-444

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Acknowledgements

• Thepatientsandtheirfamilies• ParticipatingCenters:CarolinaBioOncology Institute,ColumbiaUniversityMedicalCenter,CrossCancerInstitute,EmoryUniversity,IndianaUniversity,JohnsHopkinsUniversity,Juravinski CancerCentre,Karmanos CancerCenter,MaryCrowleyCancerResearchCenters,MedicalCollegeofWisconsin,MemorialSloanKetteringCancerCenter,MonashHealth,MountSinai,RoyalBrisbaneandWomen’sHospital,START,UniversityofCaliforniaatSanFranciscoMedicalCenter,UniversityofArizonaMedicalCenter,UniversityofChicagoMedicalCenter,UniversityofColoradoCancerCenter,UniversityofPittsburgh,UniversityofWashington,WashingtonUniversityatSaintLouis

• ColleaguesatCorvus• ColleaguesatRocheGenentech

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