MSB Trading - 2019, page-2202

Originallypostedbyotherperspective

Hiecoool2...thanksforyouprescientandexcellentpost.Myinitialthoughtsareasfollows.

1).Confirmatorytrialwasalwaysgoingtobepreconditionformarketingapproval.Thishadbeenclearlystatedclearlyininvestorbriefing/s.IthinkwearemostfortunatetohavereceivedNIHfundingforthefirsttrialof159patientsandithinkfundingislikelytocomefromthesamesourcethistime.Iwouldexpectapprox150-200patientsbeingenrolled.TheprevioustrialwasdoneindependentlyoftheCompanyandthepatientprofilingdidnotoptimisetheclinicalopportunity....forexampleenrollingyoungerfemalesundergoingbridgetotransplanttreatmentskewedtheresultsofthetrial,ratherthananoldermaleswithischemicheartdiseasehavinganLVADimplantedfor“destinationtherapy”.AddedtowhichwehadthethromboticeventsfiascowiththeLVADswhichofcoursehadnothingtodowithMesoblast.
Shareholderswhoareconcernedaboutthebalancesheetshouldbedelightedthattheapprovalpathwayforthisindicationdoesnotrequireanymajorclinicaltrialfunding...apointwhichwillnotbelostonpotentialpartners.IthinkthatMesoblastwillbeconfidentthatastheconfirmatorytrialformspartoftheirINDapplicationtheywillhavesignificantweightindeterminingallaspectsofthetrialdesign.

2)Timelines.Iwouldspeculateasfollows.Plansforthedefinitivetrialwillbetieddowninthenextmonthorso.Thepoweringofthetrialcouldbe1for1randomisedbuttheymightstaywiththe2for1oftheprevioustrial.Iwouldanticipate6-9monthsforenrolment...andafurther6-12monthstobuildadataset...followedbyaBLAsubmission....Shareholdersshouldnotethat~Mesoblastknowsthatitwilltakeapproximately12monthstocertifyandbuildupnewmanufacturingprotocolsandprocessessoeverythingisgoingaccordingtoschedule.


3)Whichsecondaryendpointswillbechosen?

Whatissoencouraginginthisstatementisadefinitiverestatementofsomeofthetrialsresults....inparticular:
”Inaposthocanalysisinpatientswithanischemiccauseofheartfailure,theseeffectsofRevascorwereevengreater,aswellasanobservedsignificantincreaseintheabilitytoweanoffdevicesupport,suggestingstrengtheningofthenativeheartmuscle”

Remember,wearetalkingaboutClassIV,orendstageheartdisease.Revascorisnowproven,notjusttostoptheseveredeteriorationoccurringbutinmanyischemiccaseswasobservedtomoderatelyimprovetheconditionofthemusclesintheleftventricle.....REMEMBEROURDREAMPHASEIIITRIALFORCHF,WHICHWILLSHORTLYCONCLUDEISLARGELYPOPULATEDBYISCHEMICPATIENTSwithClassIIandIII.
Forthereasonstatedabove,IbelieveoneofthemostimportantsecondaryendpointswillbetheabilitytosuccessfullyweanischemicpatientsofanLVADdevice.
Othersecondaryendpointswillnodoubtrelatetoqualityoflifetestsandhavebeencorrectlyidentifiedinecoool2’spost.

4)LABELEXTENSIONOPPORTUNITIES
TherealelephantintheroomisnottheLVADopportunity,whichisextremelyvaluablenicheinitself...buttheopportunitytousethistherapyinbypasssurgery.IntheUSthereareabout200,000proceduresperformedeachyear...withmorethan30%ofpatientspresentingashighriskandhavepredictedmorbidityandmortalityratesgreaterthan80%.Youcanobviouslymorethantreblethatnumberworldwide.Mostofthehighriskpatientgrouparelikelytobeischemicpatientssufferingfromcoronaryheartdisease.

5)cGVHD(Chronic)
ThemarketforChronicasopposedtoAcuteispotentiallylargerforMesoblast.Thisisbecausethisconditionissufferedevenbyrelatedand“matched’donors.Thesurvivalratesandincidenceratios(themediantimefromtransplanttodiagnosisistypically0.49years).

https://www.bbmt.org/article/S1083-8791%2814%2901247-6/pdf

TherehavealreadybeenpublicationsinboththeUSandJapanabouttheuseofmesenchymalcellsfortreatmentofchronicCGVHDandJoanneKurtzberg’strialshouldhopefullybedefinitiveconfirmationthatRemestemcel-Lhasthegreatestefficacy...particularlywithregardstothesafetyprofile.IdoubtthatanacknowledgedworldexpertlikeJoanneKurtzbergwouldbeundertakinganInvestigatorInitiatedtrialwithouthavingexperimentedherselfalready.

6)Epistaxis.
Interestinglyepistaxis(nosebleeds)wasaddedtothelistofmucosalbleedingevents.Thisisbecauseischemicpatientsoftenhavetostopanticoagulationwhentheyexperienceepistaxis..whichgreatlyincreasestheriskofthromboticevents.Eventhenosebleedsthemselvescanhaveamajortreatmentcost...apparentlyinarecenttrial,therewere5patientswhichhadtohavemajorbloodtransfusionstostopthebleeding.
ThereasonwhytheseeventsoccurmaybeafurthersymptomofArteriovenousMalformationscausedbyvascularremodelling.Angiopoetin2whencombinedwithEndothelialGrowthFactorpromotesneovascularisation.....

https://www.medpagetoday.com/cardiology/chf/79091


NOWPAYATTENTION.......THISISVERYIMPORTANT

RevascorinPatientswithmoderatetoAdvancedHeartFailure.

Wearenowinformedthatthetrialhasaccruedandvalidatedapproximately90%ofitsrequiredtargetofprimaryendpoints.ItisexpectedthatallrequiredprimaryendpointeventswillbeaccruedandvalidatedbytheendofCY2019.

AtfirstlooksthissuggestsaslowernumberofMACEeventsinthelast3months.ThesharpeyedamongyouwillrecalltheJune24th2019disclosurefromMesoblastthatinrelationtoDreamCHF:
”Thetrialhasaccruedapproximately85%ofitsrequiredtargetofprimaryendpointevents”.
Onthelateroccasiontheword“validated”wasnotused.

TheCompanyhasalreadymentionedthattheyexpecttoseea“JCurve”inMACEsowhyhasthenumberonlyincreasedby5%inthelast3months?(Suggestingarunrateof5%perquarter)...yetthetrialisnowconfidentlypredictedto“concludeandbevalidatedbytheendoftheCY2019!!!

Theanswerliesinthewaytheinformationiscollated.Aspartofthescrupulousindependentoversightofthetrial,inowunderstandthatanindependentcommitteeatHarvardMedicalSchool,examinesallclinicaldatawhichissenttotheminbatcheseverytwomonthsbytheDataMonitoringControllersothatthecauseofdeathcanbefurtherverified.ThiswouldbesupplementarytonormalproceduresfollowedaspartofissuingDeathCertificateswhicharepromptlyregisteredbythehospital.Thismeansthatthe90%numberwehavejustbeeninformedof,couldbelaggingupto1-3monthsbehindthecurrenttotal!Thefactthatwearenowforecasttohaveallresultsevaluatedwiththenext4monthssuggestsinmyopinionthatbetween94-98%ofMACEeventsmayhavealreadyoccurred....butwithoutknowingthenumberinthebacklogthisisjustawellinformedguess.Hopefullysomefurthergranularitywillbegivenonthenextinvestorcall.

Lastly,beforethemoreimpatientamongyouexpressfrustrationataconfirmatorytrial...eventhoughweareonthehomestraight...Ishouldremindinvestorsthatthepotentiallabelexpansionopportunitiesgroweverbigger...firstlyEB,thenHIEandnowcGVHD.Combinethesewithsignificantobviousopportunitiesforuse“offlabel”intheUSfortreatmentofadultswithgut,liverormultiorgansrGVHDanditisfairtoconcludethatsomeanalystsarewaybehindthecurveonestimatingpotentialcommercialisationrevenuesfromRemestemcel.Toaddinsulttoinjury,manyusehighdiscountratestocompoundthediminutionofvalue.Let’srememberthatTemcellisregularfirstlinetreatmentforadultsrGVHDinJapan!TheminutesfromtheFDAfurthervalidateMesoblastspropositionthatthedramaticdeclineinthesharepricefollowingthereleaseoftheLVADPhaseIIBtrialresultswasafailureoftheCompanyandtheanalystscommunitytocorrectlyexplainitsoutcome.IbelievethatthecurrentmarketcapitalisationofMesoblastcaneasilybejustifiedbyprospectsforUSsrGVHDandknownlabelextensioninitiativesontheirown(assumingasuccessfulBLAfilinginthenextmonthorso).Havingsaidthis,manypeoplemayfirstwantreassurancethattheCompanywilladdressthefundingshortfallof$40m?requiredbyQ22020.ThisistheamountIbroadlyestimatewillneedtobefoundtoallowtheCompanytoreachpositivecashflow(basedoncurrentknownclinicalprogrammes).Basedonitsprevioustrackrecord,theCompanypresumablyhasanumberofnondilutivewaysofraisingthiscapital(aroyaltydealforsrGVHDinEuropebeingthemostobvious)...justtrytobeonboardwhenthefundinghurdleiscleared!


Lastly,ifImaydream.Withinthenext1-10weeks?IsuggestthenumberofMACEeventswillneedtohavebeenreachedtoallowtimeforindependentverificationprocesstobeconcludedbytheendofcalendar2019.Remember,wewerepreviouslygivenguidanceofCALQ12020.WhenthishappenstherewillnoneedtowaitforfurtherMACEbeforesendingtheclinicaldataasabatch.TheDMCandtheFDAwillthenpresumablyhavenosubstantivereasontostoptheunblindingofthetrial...(evenifastrictNDAisrequiredfromprospectivepartnersbeforeresultsareofficiallyknown.)ApositiveresultwilltransformMesoblast.Itwilltakelessthan24hourstoseecertainheadlinenumbers.IF,thereisasignificantdifferenceinmortalityeventscomparedtothecontrolgroup,IbelievethatafurtherconfirmatorytrialisunlikelytoberequiredbytheFDAbeforemarketingapproval.

Pleasetakeyourtimetorereadthatlastsentence.Itisofcrucialimportance.Goodluckall.OP

Another awesome post thank you otherperspective find your posts so informative, knowledgeable and with enthusiasm that is based on insights that make sense to this tiny share holder