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NASDAQ:MEIP
StifelHealthcareConferenceNovember2017
Forward-LookingStatementsThispresentationcontains,andourofficersandrepresentativesmayfromtimetotimemake,statementsthatare“forward-lookingstatements”withinthemeaningofthesafeharborprovisionsoftheU.S.PrivateSecuritiesLitigationReformActof1995.Examplesofforward-lookingstatementsinclude,amongothers,statementsregardingourdevelopmentstrategy;potentialadvantagesofourproductcandidates;theinitiationandcompletionofpreclinicalandclinicalstudiesandthereportingoftheresultsthereof;thetimingofregulatorysubmissionsandactions;thesufficiencyofourexistingcash;andallotherstatementsrelatingtoourplans,objectives,expectationsandbeliefsregardingfutureperformance,operations,financialconditionandotherfutureevents(includingassumptionsunderlyingorrelatingtoanyoftheforegoing).Theseforward-lookingstatementsrelyonanumberofassumptionsconcerningfutureeventsandaresubjecttoanumberofrisks,uncertainties,andotherfactors,manyofwhichareoutsideofourcontrol.Importantfactorsthatcouldcauseouractualresultsandfinancialconditiontodiffermateriallyfromthoseindicatedinforward-lookingstatementsinclude,amongothers:uncertaintiesrelatingtotheinitiationandcompletionofpreclinicalandclinicalstudies;whetherpreclinicalandclinicalstudyresultswillvalidateandsupportthesafetyandefficacyofourproductcandidates;theoutcomeofregulatoryreviewsofourproductcandidates;varyinginterpretationofresearchanddevelopmentandmarketdata;risksanduncertaintiesrelatingtointellectualpropertyandtheotherfactorsdiscussedunderthecaption“Item1A.RiskFactors”inourmostrecentannualreportonForm10-KandourmostrecentquarterlyreportonForm10-Q.Anyforward-lookingstatementmadebyusinthispresentationisbasedonlyoninformationcurrentlyavailabletousandspeaksonlyasofthedateonwhichitismade.Inaddition,weoperateinahighlycompetitiveandrapidlychangingenvironment,andnewrisksmayarise.Accordingly,youshouldnotplaceanyrelianceonforward-lookingstatementsasapredictionofactualresults.Wedisclaimanyintentionto,andundertakenoobligationto,updateorreviseanyforward-lookingstatement.YouareurgedtocarefullyreviewandconsiderthevariousdisclosuresinourmostrecentannualreportonForm10-K,ourmostrecentForm10-QandourotherpublicfilingswiththeSECsincethefilingofourmostrecentannualreport.
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MEIPharma:LeveragingCoreStrengthinOncologyDrugDevelopment
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POTENTIALFORTWOREGISTRATIONSTUDIESIN2018
GrowingPipelineofDrugCandidates• Pracinostat:HDACinhibitorwithBreakthroughTherapyDesignationinpivotalPhase3study
• ME-401:DifferentiatedPI3KdeltainhibitorwithemergingdatainCLL&follicularlymphoma
• Voruciclib:SelectiveCDKinhibitorwithpotentialtoovercomeresistancetoVenclexta™
• ME-344:Mitochondrialinhibitorwithupcomingdata+Avastin®inHER2⁻breastcancer
StrongBalanceSheet$47millionincashasofSeptember30,nodebt
ExperiencedManagementTeamProventrackrecordindrugdevelopment
LeadershipTeamwithDeepExpertiseinDrugDevelopmentEXECUTIVEMANAGEMENTDanielGold,PhDPresident&ChiefExecutiveOfficerFormerChiefScientificOfficer&Founder,Favrille
RobertMass,MDChiefMedicalOfficerFormerHeadofMedicalAffairs,BioOncology,Genentech
BrianDrazbaChiefFinancialOfficerFormerChiefFinancialOfficer,HeronTherapeutics
DavidUrso,JDSVP,CorporateDevelopment&GeneralCounselFormerPrincipal,ForwardVentures/COO,TiogaPharmaceuticals
KarenPotts,PhDSVP,RegulatoryAffairsFormerSVPofRegulatoryAffairs,TriusTherapeutics
RichardGhalie,MDSVP,ClinicalDevelopmentFormerChiefMedicalOfficer,Denovo,HemaQuest,Novalar&Favrille
BOARDOFDIRECTORSChristineWhite,MD(Chair)FormerHeadofGlobalMedicalAffairs,BiogenIdec
CharlesBaltic,JDCo-HeadofHealthcare,Needham&Co.
KevanClemens,PhDFormerHeadofGlobalOncology,Roche
NickGlover,PhDPresident&CEO,SierraOncology
DanielGold,PhDPresident&CEO,MEIPharma
ThomasReynolds,MD,PhDFormerChiefMedicalOfficer,SeattleGenetics
WilliamRueckertFormerChairman,NovogenLimited
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5
DRUGCANDIDATE INDICATION/COMBINATION PRE-CLINICAL CLINICALPROOF-OF-CONCEPT PIVOTAL
Pracinostat*HDACInhibitor
AcuteMyeloidLeukemiaUnfitforintensivechemotherapyVidaza®(azacitidine)
MyelodysplasticSyndromeHigh&veryhighriskVidaza®(azacitidine)
ME-401PI3KDeltaInhibitor
CLL&FollicularLymphomaRelapsed/refractorySingleagent
IndolentLymphoma&DLBCLRelapsed/refractoryRituxan®(rituximab)
VoruciclibSelectiveCDKInhibitor
ChronicLymphocyticLeukemiaRelapsed/refractoryVenclexta™(venetoclax)
ME-344MitochondrialInhibitor
HER2-BreastCancer**Treatment-naïve,earlystageAvastin®(bevacizumab)
*PartneredwithHelsinnHealthcare,SA**Investigator-sponsoredstudy
REGISTRATIONSTUDY
ClinicalPipelineTargetingMultipleDrugPathways
Pracinostat:PotentialBest-in-ClassHDACInhibitor
BreakthroughTherapyDesignationbyFDA*
• Pracinostat+azacitidinewasgenerallywelltoleratedinthisstudy• Mostcommongrade3/4treatment-emergentadverseeventsin≥25%ofpatientsincludedfebrile
neutropenia,thrombocytopenia,anemiaandfatigue
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*BreakthroughTherapyDesignationgrantedbytheU.S.FoodandDrugAdministration(FDA)fortheinvestigationaldrugPracinostatincombinationwithazacitidineforthetreatmentofpatientswithnewlydiagnosedAMLwhoare≥75yearsofageorunfitforintensivechemotherapyPracinostatisaninvestigationalagentnotapprovedforcommercialuseintheU.S.
PRACINOSTAT+AZACITIDINE(N=50)
CRrate 42%60-daymortalityrate 10%DurationofResponse(CR/CRi) 17.2months(95%CI:10.9-21.5)1-yearsurvivalrate 62%Medianoverallsurvival 19.1months(95%CI:10.7-26.5)
Phase2studyofpracinostat+azacitidineinelderlypatientswithnewlydiagnosedAML,notcandidatesforinductionchemotherapy
PivotalPhase3StudyinAMLFirstpatientdosedinJuly2017
• Randomized,double-blind,placebo-controlledstudytoenrollupto500patients
• Primaryendpoint:Overallsurvival
• Secondaryendpoints:MorphologicCRrate,eventfreesurvival&durationofCR
• Inclusioncriteria:NewlydiagnosedAMLpatients≥18yearswhoareunfittoreceiveintensiveremissioninductionchemotherapyduetoage(≥75years)orcomorbidities
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GroupA(N=~250)Pracinostat+Azacitidine
GroupB(N=~250)Placebo+Azacitidine
NewlyDiagnosedAMLPatientsUnfittoReceiveInductionTherapy
Phase2Dose-OptimizationStudyinMDSExpecttoreportStage1resultsinH12018
• Two-stagestudy:12-15sitesinstage1;approximately25sitesinstage2
• Primaryobjectives:Safetyandtolerability;overallresponserate(ORR)
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Stage2:GroupA(N=40)Pracinostat+Azacitidine
Stage2:GroupB(N=40)Placebo+Azacitidine
Stage1(N~32)Pracinostat(45mg)+Azacitidine
Ifrateofdiscontinuation(forreasonsotherthanprogressivedisease)infirst3cycles≤20%,proceedtoStage2
PatientswithHighandVeryHighRiskMDSPreviouslyUntreatedwithHypomethylatingAgents
HelsinnanIdealPartnertoAdvancePracinostat
• CombinesMEIPharma’sclinicaldevelopmentexpertiseinoncologywithHelsinn’ssalesandmarketingexpertisewithhematologiconcologists
• Resultedin$20Minnear-termpayments,upto$444Minfuturemilestones+royalties
• $5millionequityinvestmentfromHelsinnInvestmentFund
• HelsinnresponsibleforfundingglobaldevelopmentandcommercializationforPracinostatcurrentlybeingevaluatedinAMLandotherhematologicdiseases
• SharecostofPhase2studytoexploreoptimaldosingregimenoftheinvestigationalagentPracinostat+azacitidineinhighandveryhighriskMDS
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ME-401:AHighlyDifferentiatedPI3KDeltaInhibitor
DistinctChemicalStructurefromOtherPI3KDeltaInhibitors
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IdelalisibGilead
DuvelisibVerastem
UmbralisibTGTherapeutics
ME-401MEIPharma
N
O
N
F
HN
N
N
HN
N
XZ
Y NHN
N
O
NR2
R4
R1
R3
HN
N
HN
N
N
N
O
C
Cl
H2N
N
NN
N
C
O
O
F
F
F
O
N
N
N
N
R6
R5
R4
R3
R2
H2N
INCB50465Incyte
PharmacodynamicPropertiesSuggestPotentialforImprovedSafetyandVersatilityAttributes
• LinearPKfrom10to150mg• t1/2~28hourssupportsdailydosing
• LargeVolumeofDistribution
• Preferentialaccumulationwithincells
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Outcome
• Highlypotentatlowplasmaconcentrations
• Potentialforsignificantimprovementintherapeuticwindow
• Versatilityforcombinationapproaches
ME-401DemonstratesHighBiologicPotency
• PK/PDdatawasfittoEmaxmodel
⎼ EC50=0.6ng/ml(1.0nM)
⎼ EC90=5.2ng/ml(8.9nM)
• Dailydosingof60mginPhase1bstudiesyieldscontinuousplasmaconcentrations≈3XabovetheEC90
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PlasmaConcentration(ng/ml)
%Inhibitio
nof
Stim
ulationof
Bas
ophils
01020304050
120
100
80
60
40
20
0
PK/PDDataEmaxModelEC9060mgCmin
*InhibitionofbasophilactivationbyFcεR1antibodyfollowingsingleascendingdosinginhealthyvolunteers
Pre-ClinicalandClinicalDataSuggestWideTherapeuticWindow
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*Source:CHMPassessmentreport
DogNOAEL RecommendedStartingDose(150mgBID)
Idelalisib*
Leve
lofD
rugEx
posu
re
DogNOAEL MinimumBiologicallyEffectiveDose(60mgQD)
ME-401
Leve
lofD
rugEx
posu
re
Exposure(AUC)inhumansvs.NoObservedAdverseEffectLevel(NOAEL)indogs
PhaseIbStudyinCLLandFollicularLymphoma
Keyobjectives:
• MinimumBiologicallyEffectiveDose(mBED)
• EfficaciousDose
• MaximumToleratedDose(MTD)
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DoseEscalationStartat60mg
CohortExpansionIfnoDLTsand≥2responsesin6patients,thenexpandcohortto12
DoseescalatetoMTD
EfficaciousDosemBED
Single-AgentRegistrationStudyCombinationStudies
Keyeligibility:
• Relapsed/refractoryCLLorfollicularlymphoma
• Nopriortherapyw/PI3Kdeltainhibitors
• Nopriortherapyw/BTKinhibitorsunlessintolerant
Phase1bStudyinCLLandFollicularLymphomaEmergingSafetyandEfficacyData• 28patients(13at60mg,9at120mg,6at180mg)enrolled;25evaluableforsafety(range=1-11mo.,median=4.3mo.);18patientsevaluableforefficacy
– Responserateinboth60mgand120mgcohortsboth>50%
• Nodoselimitingtoxicitiesatnoted
• Plantosubmitlong-termsafetyandefficacydataon~36patientsforpresentationatscientificmeetinginQ22018
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QualitativeAssessmentoftheUnmetMedicalNeedinRelapsed/RefractoryFollicularLymphoma
Low Low to Moderate Moderate Moderate to High High
4% 4% 28% 48% 16%
92%
Current unmet need in relapsed/refractory FL
Low Low to Moderate Moderate Moderate to High High
0% 16% 68% 16% 0%
100%
Overall satisfaction with drugs currently available to treat relapsed/refractory FL
*Source:MEIPharmaPrimaryMarketResearch;n=25U.S.andEUPhysicians
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ImportanceofIdelalisibinRelapsed/RefractoryFollicularLymphoma:PotentialforaSaferPI3KDelta*
Low Low to Moderate Moderate Moderate to High High
0% 0% 4% 40% 56%
96%
Low Low to Moderate Moderate Moderate to High High
0% 4% 28% 56% 12%
84%
Importance of Idelalisib in treating/managing relapsed/refractory FL patients
Importance of novel PI3Kδ inhibitor without the negative aspects of Idelalisib
*Source:MEIPharmaPrimaryMarketResearch;n=25U.S.andEUPhysicians
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Voruciclib:ASelectiveCDKInhibitor
Clinical-StageAssetwithClearDevelopmentPath
• ObtainedrightstovoruciclibinSep2017for$2.9Minnear-termpayments⎼ $2Mincrementalpaymentuptoregulatoryapprovaloffirstindication⎼ Additionalpotentialmilestonesofupto$179M,mid-single-digittieredroyalties
• Oral,selectiveCDKinhibitordifferentiatedbypotentinhibitionofCDK9⎼ CDK9showntosuppressMCL1,aknownmechanismofresistancetoBCL2inhibitors
• Pre-clinicaldatashowssynergywithBCL2inhibitorVenclexta™(venetoclax)
• Testedinmorethan70patientsinmultiplePhase1clinicalstudies– ManageableGIsideeffectsconsistentwithotherCDKinhibitors
• PlannedPhase1/2studyinBcellmalignanciesandthen+venetoclaxinR/RCLL
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MCL1:TheAchillesHealforVenetoclax
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• VenetoclaxinhibitsBCL2butnotanti-apoptoticfamilymemberMCL1
• IncreasedMCL1isanestablishedresistancemechanismtovenetoclax1
1Blood.2016Jun23;127(25):3192-201
Voruciclib:PotentialtoOvercomeVenetoclaxResistance
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• Cyclindependentkinases(CDKs)areafamilyofkinasesinvolvedincellcycleandtranscriptioncontrol
• VoruciclibisanoralCDKinhibitorwithlownMinhibitionofCDK9,4/6&1
• InhibitionofCDK9resultsinsuppressionofMCL1levels,promotingapoptosisinMCL1dependentcells
Pre-ClinicalStudiesShowInhibitionofMCL1andSynergisticCellDeath*
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Vehicle Voruciclib Venetoclax Voruciclib+VenetoclaxMCL
-1/D
API/FT
M
*NUDHL1diffuselargeB-celllymphoma(DLBCL)modelusingPresage’sCIVO™intratumoralmicrodosingplatform
CC3/D
API/FT
M
MCL1Levels
CellDeath
Voruciclib/VenetoclaxSynergyObservedinvivo*
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*U2932diffuselargeB-celllymphoma(DLBCL)model
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ClinicalExperience
• Dosedfrom75-500mgQDinPhase1solidtumorstudies;MTD350mg
• Orallyavailablew/half-lifeof>24hours
• MostcommonAEs:diarrhea,nausea,vomiting,fatigue
• Twoi.v.CDKinhibitorswithCDK9activityhavebeenevaluatedinCLL
⎼ Alvociclib(Sanofi),N=164:PR=25%,TLS=25%(discontinuedduetosafety)
⎼ Dinaciclib(Merck),N=44:PR=40%,TLS=5%(discontinuedinCLLforprogramre-prioritization;currentlyinmultiplePhase1studieswithPD-1)
PotentialforCombinationwithVenetoclaxatSafe,EfficaciousDose
• Phase1PKresultssuggeststeadystatelevels>1.5μMachievablewith150mgdailydosing
• Inducesapoptosisat0.5–1μMin>50patient-derivedCLLsamples(right)1
• SuppressionofMCL1Ipre-clinicalstudiesalsoobservedatconcentrations0.5–1μM
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1PLoSOne.2015Nov25;10(11):e0143685
Voruciclib, µM
Phase1/2StudyinRefractoryCLLExpecttodosefirstpatientinQ22018
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Determinesafety,efficacyandMCL1inhibitionofsingle-agentvoruciclib.MonitorMCL1levels;Beginstage2concurrentlyoncesafetyofinitialdoseshavebeenestablished
Stage3Cohortexpansionofvoruciclib+venetoclax
Stage1Doseescalationofsingle-agentvoruciclib
Stage2Doseescalationofvoruciclib+venetoclax
EstablishrecommendedPhase2doseofvoruciclibincombinationwithvenetoclax
Evaluatesafety,responserateandrateofminimalresidualdisease(MRD)ofvoruciclibincombinationwithvenetoclax
Voruciclib+VenetoclaxNotOnlyaCLLStory:OpportunitiesinDouble-HitLymphoma
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• SubtypeofdiffuselargeB-celllymphoma(DLBCL)characterizedbyrearrangementsofMYCandBCL2(mostcommon)orBCL6⎼ Poorprognosis,significantunmetneed
• VoruciclibinhibitsMYCproteinexpression(right)
• LowresponseratetoBCL2inhibitorvenetoclaxasmonotherapyinDLBCL(18%ORR;n=34)1
• VoruciclibsynergisticwithvenetoclaxinmultipleDLBCLmodels2
1JClinOncol.2017Mar10;35(8):826-833;2ASH2016:4167
ME-344:ANovelTumorSelectiveMitochondrialInhibitor
ME-344:ANovelMitochondrialInhibitor
• MechanismofactiondirectlytargetsmitochondrialOXPHOScomplexI1,resultinginrapidlossofcellularenergy(ATP)
• EvidenceofsingleagentactivityinPhase1dose-escalationstudyinrefractorysolidtumors2
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1AmJCancerRes.2015Jan15;5(2):689-701;2Cancer.2015Apr1;121(7):1056-63
TheProblem:TumorCellMetabolicPlasticity
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• Invivo,tumorcellsdisplaymetabolicplasticityswitchingbetweenaerobicglycolysisandmitochondrialmetabolism
• Pre-clinicaldatademonstrateabilityofVEGFinhibitorstomodulatetumor’sglycolyticdependence1,2
• Investigator-sponsoredstudyofME-344incombinationwithAvastin®inHER2-negativebreastcancernowactivelydosingpatients
1JPharmacolExpTher.2016Aug;358(2):199-208;2CellRep.2016Jun21;15(12):2705-18
ClinicalStudyinHER2-NegativeBreastCancer*DataexpectedinDecember2017
• Prospective,randomizedstudybeingconductedat6sitesinSpain
• Primaryobjective:Mitochondrialswitchchangesfrombaseline
• Secondaryobjectives:Evidenceofbiologicanti-tumoractivityandsafety
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Biopsy/Analysis
GroupA(N=20)ME-344+Avastin®
GroupB(N=20)Placebo+Avastin®
SurgeryonDay28/Analysis
*SponsoredbySpanishNationalCancerResearchCentre
StrongIntellectualPropertyProtection
Pracinostat(formerlySB939)• 4issuedU.S.and77issuedforeignpatents
⎼ 2U.S.and8foreignapplicationspending• CompositionofmattertoMay2028inU.S.
⎼ May2033,whichincludesupto5yearsofpatenttermrestorationinU.S.
Voruciclib(formerlyP1446A)• 2issuedU.S.and14issuedforeignpatents
⎼ 6U.S.and11foreignapplicationspending• CompositionofmattertoSep2028inU.S.
⎼ Sept2033,whichincludesupto5yearsofpatenttermrestorationinU.S.
ME-401(formerlyPWT143)• 2issuedU.S.patent
⎼ 1U.S.and21foreignapplicationspending• CompositionofmattertoDec2032inU.S.
⎼ Dec2037,whichincludesupto5yearsofpatenttermrestorationinU.S.
ME-344(formerlyNV-344)• 3issuedU.S.and18issuedforeignpatents
⎼ 3U.S.and7foreignapplicationspending• PharmaceuticalcompositiontoNov2031inU.S.
⎼ Nov2036,whichincludesupto5yearsofpatenttermrestorationinU.S.
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DeliveringonNear-TermMilestones
Pracinostatü FirstpatientdosedinPhase2dose-optimizationstudyinMDSü FirstpatientdosedinpivotalPhase3studyinAMLq Datafromstage1ofPhase2dose-optimizationstudyinMDS(1H2018)ME-401ü Demonstratesafe,efficaciousdoseinsingle-agentPhaseIbstudyinCLL&follicularlymphomaü InitiatecombinationstudywithRituxan®inindolentlymphoma&DLBCL(Q42017)q DatafromPhaseIbstudyinCLL&follicularlymphoma(Q22018)q Initiatesingle-agentregistrationstudyinR/Rfollicularlymphoma(Q22018)Voruciclibq InitiatePhase1/2studywithvenetoclaxinrelapsed/refractoryBcellmalignancies(Q22018)ME-344q Datafrominvestigator-sponsoredstudywithAvastin®inHER2-negativebreastcancer(1H2018)
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Pracinostat,ME-401,voruciclibandME-344areinvestigationalagentsandhavenotbeenapprovedforcommercialuseintheU.S.
NASDAQ:MEIP
StifelHealthcareConferenceNovember2017