COMPANY PRESENTATION - Akari Therapeutics · * PNH: Paroxysmal nocturnal hemoglobinuria; aHUS:...
Transcript of COMPANY PRESENTATION - Akari Therapeutics · * PNH: Paroxysmal nocturnal hemoglobinuria; aHUS:...
August2017
NASDAQ:AKTX
CopyrightAkariTherapeu=cs,Plc2017
COMPANYPRESENTATION
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Cau$onaryNoteRegardingForward-LookingStatements
Certain statements in this presenta.on cons.tute "forward-lookingstatements"within themeaning of Sec.on 27Aof the Securi.esActand Sec.on 21E of the Securi.es Exchange Act and are usuallyiden.fied by the use of words such as "an.cipates," "believes,""es.mates," "expects," "intends," "may," "plans," "projects," "seeks,""should," "will," and varia.ons of suchwords or similar expressions.Weintendtheseforward-lookingstatementstobecoveredbythesafeharborprovisionsforforward-lookingstatementscontainedinSec.on27Aof the Securi.esAct and Sec.on21Eof the Securi.es ExchangeAct and are making this statement for purposes of complying withthosesafeharborprovisions.Theseforward-lookingstatementsreflectourcurrentviewsaboutourplans,inten.ons,expecta.ons,strategiesandprospects,whicharebasedontheinforma.oncurrentlyavailabletousandonassump.onswehavemade.Althoughwebelievethatourplans,inten.ons,expecta.ons,strategiesandprospectsasreflectedinorsuggestedbythoseforward-lookingstatementsarereasonable,wecan give no assurance that the plans, inten.ons, expecta.ons orstrategies will be aJained or achieved. Furthermore, actual resultsmay differ materially from those described in the forward-lookingstatementsandwillbeaffectedbyavarietyof risksand factors thatare beyond our control. Risks and uncertain.es for our companyinclude,butarenotlimitedto:needsforaddi.onalcapitaltofundouropera.ons; an inability or delay in obtaining required regulatoryapprovals forCoversinandanyotherproductcandidates,whichmayresult in unexpected cost expenditures; risks inherent in drugdevelopment in general; uncertain.es in obtaining successful clinicalresultsforCoversinandanyotherproductcandidatesandunexpectedcoststhatmayresulttherefrom;failuretorealizeanyvalueofCoversinandanyotherproductcandidatesdevelopedandbeingdeveloped inlightof inherent risksanddifficul.es involved insuccessfullybringingproductcandidatestomarket;inabilitytodevelopnewproduct
candidatesandsupportexis.ngproducts;theapprovalbytheFDAandEMA and any other similar foreign regulatory authori.es of othercompe.ngorsuperiorproductsbroughttomarket;risksresul.ngfromunforeseen side effects; risk that the market for Coversin or otherproductcandidatesmaynotbeaslargeasexpected;inabilitytoobtain,maintainandenforcepatentsandotherintellectualpropertyrightsorthe unexpected costs associatedwith such enforcement or li.ga.on;inability to obtain and maintain commercial manufacturingarrangementswith thirdpartymanufacturersorestablishcommercialscalemanufacturingcapabili.es;unexpectedcostincreasesandpricingpressures; and uncertainty of our ability to raise capital and ourinabilitytomeetworkingcapitalneeds.Manyofthesefactorsthatwilldetermine actual results are beyond our ability to control or predict.For a discussion of the factors that may cause our actual results,performance or achievements to differ materially from any futureresults, performance or achievements expressed or implied in suchforward-lookingstatements,seethe“RiskFactors”sec.onofourmostrecentlyfiled20F.Exis.ngandprospec.veinvestorsarecau.onednotto place undue reliance on these forward-looking statements, whichspeak only as of the date hereof. The statements made in thispresenta.onspeakonlyasof thedatestatedherein,andsubsequentevents and developmentsmay cause our expecta.ons and beliefs tochange.Unlessotherwiserequiredbyapplicablesecuri.eslaws,wedonotintend,nordoweundertakeanyobliga.on,toupdateorreviseanyforward-looking statements contained in this presenta.on to reflectsubsequentinforma.on,events,resultsorcircumstancesorotherwise.While we may elect to update these forward-looking statementspublicly at some point in the future, we specifically disclaim anyobliga.on to do so, whether as a result of new informa.on, futureeventsorotherwise,exceptasrequiredbylaw.
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Developingthenextgenera$onofrare&orphanan$-inflammatorytherapies
AkariMissionStatement
Tickshaveundergone300millionyearsofnaturalselec.onto produce inhibitors that bind to key inflammatorymediatorsandarewell tolerated inhumans. Ouruniquemoleculesarederivedfromtheseinhibitors
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Exploi$ngEvolu$onaryBenefitsofTick-DerivedProteins
Ticksalivaryproteinsworkbyinhibi.nghostimmuneresponses,enabling.cktorepeatedlyfeedwithoutdamagefromhostinflammatoryresponse
EFFICIENT
TARGETED
Targetearlyinflammatorymediators
Specificbindingavoidsoff-targeteffects
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AkariHighlights
*PNH:Paroxysmalnocturnalhemoglobinuria;aHUS:Atypicalhemoly=c-uremicsyndrome;AKC:Atopickeratoconjunc=vi=s;BP:BullousPemphigoid
Developing.ck-derivedproteinstoinhibitearlyinflamma.on
Threeseparatedevelopmentprograms,eachfocusedondis.nctinflammatorypathways
1)Complementprogram• PNH*-projectedPhaseIIIstart–4Q2017• aHUS*-projectedPhaseIIstart–4Q2017• Once-weeklydosingmoleculeindevelopment
2)DualC5&leukotrieneB4(LTB4)program• AKC*&BP*-projectedPhaseIIstarts–1Q2018
3)Scien$ficdevelopmentprogram• Other.ck-derivedandengineeredmolecules
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StrategicPosi$oning
Ac.vePNH&upcomingaHUStrialsGrowinglistofothertargets
Poten.alfor20-30%marketshare
Poten.altoachievedominantmarketshareassoleprovider
Complementinhibi$on
Expectedtobe~$5billionpeakmarket
SubQdeliverydifferen.atedagainstcurrentIVstandardof
care
Leukotriene+Complementinhibi$on
Developingorphanmarket
Differen.atedMechanismofAc.on
Ac.veAKC,BP,Systemicprograms
andothertargetswithhighdegreeofunmetneed
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PhaseIII
AkariPorYolioBuildsOnComplementExperience
TissueTargeted(NMJ)
ComplementSystem(C5)Coversin™
CoversinLA™
LTB4
BioamineSystem
LTB4(L-Coversin™)
LTB4LA
Histaminebinding
Serotoninbinding
PhaseIIPhaseI
Coversin-LTB4+C5
PreclinicalDiscovery
COMPLEMENTPROGRAM
TreatmentDura$on,Safety,andTolerabilityOfPa$entsTreatedwithCoversin
8
17months
Eculizumab-resistantPNHpa$ent(CONSENT)
Con$nuingPhase2PNHpa$ents(COBALT)*
Pa$entwhodidnotcompletePhase2study(COBALT)
• Drugwelltoleratedbypa.ents• NoSAEsrelatedtoCoversin• CONSENTpa.entandthe4con.nuingCOBALTpa.entsareself-dosingandhavehadnotransfusionsduringorposttrial(todate)
• Pa.entsdeveloplow.teran.bodiesbetween2-13weeksaqerstar.ngCoversin
• An.bodiesnon-neutralizinginly.cassay
17Months
7Months
6Months
5Months
4Months
43Days
*Nowinlonger-termsafetystudy(CONSERVE)
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ComplementPathwayPosi$oning
• TwoongoingPhaseIIPNHprograms–CONSENTandCOBALT;andalong-termsafetystudy-CONSERVE
• ResistantPNHtrial(CONSENT)–1pa.ent‒ Currentlyrecrui.ng‒ Pa.enthasbeenonCoversinsinceFebruary2016
• NaïvePNHtrial(COBALT)-5pa.ents‒ All4con.nuingpa.entshavenowenteredlongterm
safetystudy(CONSERVE)‒ Onepa.entwithdrawnatDay43duetosuspected
comorbidityunrelatedtotreatment‒ Currentlyrecrui.ng2-3addi.onalpa.ents(protocolbeing
amendedtoinves.gatehigherdosing)
• aHUSPhaseIItrial–upto10pa.ents
10
0
200
400
600
800
1,000
1,200
1,400
Posi$veResponseFor15Months*InEculizumab-ResistantPNHPa$entTreatedWithCoversin
CH50<8.0UEq/mL(belowlevelofdetec$on)Nohemoly$cepisodes;nodosechanges;symptomfree;twicedailyselfinjec$on
Pa=enttreatedpursuanttoanapprovedclinicalprotocolintheNetherlands2016EH,SaskiaLangemeijier,UniversityofRadboud,Nijmegen*Note:allavailableLDHdatashown;pa=enthasnowbeenontreatmentwithCoversinfor17months
LDH(IU
/ml)
Weeks8 16 24 320 40 48 56 64
1.5ULN
LDH
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Phase2PNHTrialsUpdate
Allfivecon.nuingpa.ents(inCONSENTandCOBALT)onongoingtreatmenthaveexperienced:
• Daily(COBALT)ortwicedaily(CONSENT)subQself-administra.on• Noneutralizingan.bodies• NoSAEsrelatedtoCoversin• AEs(includingmild/moderateinjec.onsitereac.ons)
• CH50belowlevelofquan.fica.on• LDHreduc.on• Notransfusions(3of5con.nuingpa.entsrequiredtransfusioninthe12monthspriortoreceivingCoversin)
• Stablehemoglobin
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LDH plotted as a multiple of ULN 4 patients who remained in COBALT
012345678
0 14 28 42 56 70 84
LDHxU
LN
Daysincefirstdose
MeanPatientAPatientBPatientCPatientD
0
20
40
60
80
100
120
140
0 14 28 42 56 70 84
AST(U/L)
Daysincefirstdose
MeanPatientAPatientBPatientCPatientD
Aspartate aminotransferase (AST) 4 patients who remained in COBALT
DeclinesinBloodMarkersofHemolysis–AllFourCon$nuingCOBALTPhaseIIPa$ents
Afiqhpa.ent(Pa.entE),withdrawnDay43duetosuspectedcomorbidity,hadbaselineLDHof4.8XULN&LDHof2.7XULN&2.8XULNatDay28&42,respec.vely;
baselineASTwas68U/Landfellto33and43U/LatDay28and42,respec.vely
MeanLDH1.8XULN(Day28-90)
AST83+19.2U/Latbaseline;28.5+3.3U/LDay90Coversin
NOTE:Day0dataforpa=entsAandDwasrecordedwithinsixweekspriortotrialentry
PackedRedBloodCells(PRBC)TransfusedPriortoandDuring90DayCOBALTTrial
MonthspriortostartofTrial
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Pa.entsAandEhadnotransfusionsinthe12monthsprecedingtheCOBALTtrialorwhileinthetrial.Pa.entEwaswithdrawnfromthetrialatDay43
0
2
4
6
8
10
12
12-9 9-6 6-3 3-0 0-3
Trial
Pa.entB
Pa.entDPa.entC
Pa.entA
Pa.entE
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PlannedPNHPhaseIIITrialsCAPSTONEandASSET
• TwoPNHPhaseIIIclinicaltrials:‒ Naïvepa.ents(CAPSTONE)‒ Switch(ASSET)
• CAPSTONE:Naïvepa.entsrandomizedtoCoversinplusstandardofcarevs.standardofcare
• ASSET: Eculizumab-treatedpa.entsrandomizedtoremainoneculizumaborswitchtoCoversin
• Indiscussionwithregulatorsregardingtrialdesigns• CAPSTONEcurrentlyprojectedtocommence4Q2017
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CoversinTarge$ngAtypicalHemoly$cUremicSyndrome(aHUS)
• Chronicandlife-threateninggene.cdiseasecharacterizedbymicroangio-pathichemoly.canemia,thrombocytopenia,andkidneyinjury
• EfficacyofC5inhibi.oninaHUSdemonstratedbytheapprovalofeculizumabforthisindica.on
• aHUSphysicianshaveexpressedsupportforonce-dailyCoversin– Moretherapeu.cflexibilityforepisodicpa.ents– Pa.entconvenience
• PhaseIItrial–upto10naïvepa.entsatsevensitesacrossEurope,projectedtobeginin4Q2017
DUALC5ANDLEUKOTRIENEB4(LTB4)PROGRAM
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DualLeukotrieneandComplementInhibi$onbyCoversinHasPoten$alInWideRangeofDiseaseswithUnmetNeed
ComplementOnly
Leukotrine&Complement
Asthma
RheumatoidArthri.sPAH
Trauma
Sjögren’s
Bronchioli.sobliterans
COPD
AATD
BullousPemphigoid
Goodpasture’s
AKC
DryEye
PNH aHUS
MucousMembranePemphigoid
MG NMO
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TwoPhaseIILeukotriene/ComplementTrialsProjectedtoStartin1Q2018
• PhaseIIprograms‒ AKC(atopic
keratoconjunc.vi.s)-eye(topicaldrops)
‒ BP(bullouspemphigoid)–skin(subQ)
• Severalseverelungcondi.onsareimpactedbycomplementandleukotrienepathwayswithzileutonandmontelukastbothprescribed
• Dualac.vitycreatespoten.alforuniquetreatmentop.on
DatafromPneumolabs2017
Dualac$on(Coversin)moreeffec$vethanC5-only(saturatedCoversin)or
Zileutonaloneinmousemodel
Coversin
(inhibitsC5+LTB4
)SaturatedCo
versin
(inhibitsC5on
ly)
Zileuton
(inh
ibits
Leuk
otrie
ne/
LTB4
)
NeutrophilrecruitmenttomouselunginducedbyLPSinpresenceof
CoversinorZileuton
Coversin&L-CoversinPoten$allySuperiorStrategytoTargetLTB4
PreviousstrategiestotargetLTB4sufferedfromalackofselec$vity;benefitsofreducingLTB4wereoffsetbyoff-targeteffects
CoversinandL-CoversincaptureLTB4withinaninternalbindingsite• Directlyandspecifically“mopup”LTB4
withoutperturbingotherpathways• UniqueLTB4targe.ngselec.vity
‒ Expectednottoreducean.-inflammatorylipoxins
‒ DoesnotinhibitPGP(anan.-inflammatoryagent)degrada.on
Roversi,P.etal.,JBiol.Chem.2013
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LTB4Interven$onStrategies
Arachidonicacid
LTA4
LipoxinsLTB4LTC4LTD4LTE4
5-LOFLAP
LTA4HLTC4S
Lipoxygenases
Pro-inflammatory
Anti-inflammatory
Spasmogenic
Zileuton
GSK2190915DG-031
MK-0633TA-270
5-LO/FLAPinhibitors
Reducesan.-inflammatorylipoxins
BLT1/BLT2antagonists
Realiza.onthatan.-inflammatorymediatorsalsosignalthroughBLT1/BLT2
LTA4Hinhibitors
Secondaryan.-inflammatoryroleforLTA4H
indegradingpro-inflammatory/remodelling
mediatorPGPBLT1 BLT2
LY-293111ONO-4057BIIL284CP105696
DG051JNJ-40929837AcebilutsatUbeniimex
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Limita$onsofOtherLTB4Inhibitors
DUALACTIONEYE(AKC)ANDSKIN(BP)PROGRAM
Collabora.onwithMoorfieldsHospital(Ins.tuteofOphthalmology)EICpre-clinicalmodelofsevereeyesurfaceinflamma.on
DemonstratedBenefitinMouseModelLate-PhaseOcularInflamma$on
• C57/Bl6micesensi=zedtoOVAfor14days• OVAeyesurfacechallengefor6dayspostsensi=za=on(days0–6)• Coversinappliedoncedailyondays3–6a_erinflammatoryresponsewellestablished• Maximumeffectseena_er3daysofCoversintreatment(latephaseofinflamma=on)
• Coversin-64%reduc$onininflammatoryscorecomparedtoplaceboinmousemodel
• Timingindica.veofTcellresponse• Historicalcomparison*:‒ CyclosporinA(0.1%)-43%reduc.on
‒ Betamethasone(0.1%)-nosignificantreduc.on0
12345678
Day3 Day4 Day5 Day6
Inflamma.
onsc
ore
EffectofCoversinonOVAinducedinflamma$on(n=16pergroup)
Placebo Coversin
p<0.0001
p<0.01
*ShiiD,NakagawaS,YoshimiMetal.2010;BiolPharmBull33(8):1314–1318 22
AtopicKeratoconjunc$vi$s(AKC)
• Severeeyesurfaceinflamma.oncausinginfiltra.onofimmunecellssuchasneutrophilsandTcells.Acauseofblindnessworldwide
• Topicaldrugs,suchassteroidsorcyclosporin,oqennoteffec.veorcannotbegivenchronically
• InAKCdisease,despitebestcurrenttreatmentmanypa.entsprogresstoseverecornealinvolvement
• BothcomplementandLTB4knowntobeinvolved
• Progressestoaffectthecorneaandmayleadtolossofvision.Botheyesaffected
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• Therapeu.csuccessinthisindica.oncouldopenupothercicatrisingeyesurfacecondi.ons
• PhaseI/IIrandomized,doublemasked,placebo-controlledtrialatMoorfieldsEyeHospitalandRoyalLiverpoolHospitalprojectedtostart1Q2018
CoversinDemonstratedBenefitinBullousPemphigoidModel
PreclinicalpassivemousemodelfromDr.SadikinLubeck,GermanyLeadingBullousPemphigoidcenter
P=0.0023betweenvehicleand250µg/kg
• ~60%reduc.oninaffectedareaonCoversin(SubQ)comparedtovehicleorsteroidinmousemodel
• Cleardoseresponse
Vehicle 250µg/kgCoversin
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BullousPemphigoid(BP)SignificantUnmetNeed
• Immunecomplexdeposi.onini.atescomplementcascadeandinflammatoryprocess• LTB4recruitsneutrophilstodermis-epidermisjunc.onandamplifiesinflamma.on• PhaseIIopenlabeltrialagainststandardofcareprojectedtostartin1Q2018inthreecentersinEurope
SCIENTIFICDEVELOPMENTPROGRAM
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AkariDiscovery
PlaYorm
Coversinengineeredmoleculestargetedtocomplementpathway
OtherAkari.ck-derivedmolecules
• Eicosanoidpathway(LTB4only)L-Coversin(lung)
• Bioaminepathway
• Extendedhalflife(LA)
‒ Ligandcapturepreven.ngac.ononmul.pleGPCRs
‒ Similarbiophysicalproper.estoCoversin
• Tissuetarge.ng(NMJ*)(MyastheniaGravis)
*Neuromuscularjunc=on(NMJ)isthesiteofcommunica=onbetweenmotornerveaxonsandmusclefibers
Coversin
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CoversinLA:OnceWeeklyFormula$on
0
20
40
60
80
100
120
0.01 0.1 1
%TotalLysis
CoversinEculizumabPASCoversinCoversin&Eculizumab
Drugconcentra$on(µM)
Inhibi$onofcomplementalterna$vepathwayrabbitredbloodcelllysis
PASCoversin
Coversin
5%
HumanPKsimula$onoffreeC5followingsingledoseinjec$onpoten$alforweeklydosing
• Terminalhalflifeinhumanses.matedatfourdaysbasedonpharmacokine.c(PK)datainmiceandrats
• Cleanini.altoxicologyprofilecomparabletounmodifiedCoversin• PhaseIclinicalstudyplannedfor2018Sources:BASTInc.Limited,UCLLaboratories
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FinancialSummaryMarch31,2017
• ADS*outstanding 11,776,934
• ADSFullyDiluted 12,583,641
• CashandCashEquivalents** $35.1m(nodebt)
* EachADSrepresents100ordinaryshares**Includesshort-terminvestments
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AkariClinicalProgramHighlights
Complementprogram
• PNH-projectedPhaseIIIstart–4Q2017 -addi.onalPhaseIIpa.ents–4Q2017• aHUS-projectedPhaseIIstart–4Q2017• CoversinLA-projectedPhaseIstart–4Q2018
DualC5&leukotrieneB4(LTB4)program
• AKC&BP-projectedPhaseIIstarts–1Q2018
• Threeofthefourcon.nuingpa.entswereupdosed– Pa.entAandBwereupdosedfrom30mgto45mgoncedailyatDays40and54,respec.vely– Pa.entCwasupdosedto22.5mgtwicedailyatDay24andmovedto45mgoncedailyatDay67– Pa.entB,thelastintodate,didnotseeadeclineinLDHwithupdosing,althoughhishemoglobinlevelroseaqerDay67
• PrimaryendpointofLDH<1.8XULNatDay28wasachievedbytwoofthefivepa.ents
• LDHasamul.pleofULN(xULN)forthe5pa.ents(A,B,C,DandE)atDay28wasrespec.vely1.4,2.2,2.5,1.4and2.7
• Pa.entEwaswithdrawnatDay43• Forthefourcon.nuingpa.ents,xULNatDay60was1.5,2.1,1.8and1.5;andatDay90,1.6,2.4,2.0and1.9
COBALTPhaseIIDosingandResponseSummary
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August2017
NASDAQ:AKTX