vision is our mission - Ophthalmology Innovation …•Many ocular orphan indications are due to genetic defects •Potential to cure diseases with significant unmet medical need •Eye

NASDAQ:OPHT October2018

visionisourmission

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AnystatementsinthispresentationaboutOphthotech’s futureexpectations,plansandprospectsconstituteforward-lookingstatementsforpurposesofthesafeharborprovisionsunderthePrivateSecuritiesLitigationReformActof1995.Forward-lookingstatementsincludeanystatementsaboutOphthotech’s strategy,futureoperationsandfutureexpectationsandplansandprospectsforOphthotech,andanyotherstatementscontainingthewords“anticipate,”“believe,”“estimate,”“expect,”“intend”,“goal,”“may”,“might,”“plan,”“predict,”“project,”“target,”“potential,”“will,”“would,”“could,”“should,”“continue,”andsimilarexpressions.Inthispresentation,Ophthotech’s forward-lookingstatementsincludestatementsabouttheimplementationofitsstrategicplan,Ophthotech’s projecteduseofcashandcashbalances,thetiming,progressandresultsofclinicaltrialsandotherresearchanddevelopmentactivities,thepotentialutilityofitsproductcandidatesandthepotentialforitsbusinessdevelopmentstrategy,includingitscollaborativegenetherapyresearchprogramsandanypotentialin-licenseoracquisitionopportunities.Suchforward-lookingstatementsinvolvesubstantialrisksanduncertaintiesthatcouldcauseOphthotech’s clinicaldevelopmentprograms,futureresults,performanceorachievementstodiffersignificantlyfromthoseexpressedorimpliedbytheforward-lookingstatements.Suchrisksanduncertaintiesinclude,amongothers,thoserelatedtotheinitiationandtheconductanddesignofresearchprogramsandclinicaltrials,availabilityofdatafromtheseprograms,expectationsforregulatorymatters,needforadditionalfinancingandnegotiationandconsummationofin-licenseand/oracquisitiontransactionsandotherfactorsdiscussedinthe“RiskFactors”sectioncontainedinthequarterlyandannualreportsthatOphthotech fileswiththeSecuritiesandExchangeCommission.Anyforward-lookingstatementsrepresentOphthotech’s viewsonlyasofthedateofthispresentation.Ophthotech anticipatesthatsubsequenteventsanddevelopmentswillcauseitsviewstochange.WhileOphthotech mayelecttoupdatetheseforward-lookingstatementsatsomepointinthefuture,Ophthotech specificallydisclaimsanyobligationtodosoexceptasrequiredbylaw.

Forward-lookingStatements

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• Market:Largeandorphanindications

• Pipeline:Expansionthroughbusinessdevelopmentactivities

• Execution:Uniquein-houseexpertiseinclinicaldevelopment

• StrongCashPosition:Drivefuturegrowth

ValueCreation:BuildingaLeadingRetinaCompany

DevelopingTransformativeGeneTherapiesandNovelTherapeuticsforRetinalDiseases

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• Therapeutics– Deepunderstandingandexpertiseinophthalmicdrugdevelopment

• Multipleretinaspecialistsinmanagement• Highlyexperiencedclinicaldevelopmentteam

– Strongglobalnetwork• WellknownKOLs• Experiencedclinicalinvestigators

• GeneTherapy– NovelandcuttingedgeAAVgenetherapy:

• Dualfunction(knockdown+replace)singleAAVvectorstrategy:RHO-adRP• Minigene strategy:LCA10(CEP290)andStargardt disease(ABCA4)*

• AAVgenedeliverymethods*

Multi-ModalityApproach:MaximizeProbabilityofSuccess

*SponsoredresearchwithUMASSMedicalSchool;optiontoin-licenseresultingIP

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Indication Phase1 Phase2 Phase 3 Status

Wet AMD (in combo with anti-VEGF)

• Zimura:Phase2aongoing• Initial top-linedataexpected late2018

GA secondary to Dry AMD (monotherapy)

• Zimura:Phase2bongoing• Initialtop-linedataexpectedQ42019

STGD1(monotherapy) • Zimura:Phase2bongoing*• Initialtop-linedataexpected2020

IPCV(incombowithanti-VEGF)

• Zimura:Phase2aongoing

RHO-adRPAAVvector

• UPenn sponsoredresearchongoing• IND-enablingstudiesplannedfor2019• Phase1/2expectedtoinitiatein2020

NovelGeneDeliveryMethods • UMMSsponsoredresearchongoing+

LCA10“minigene”(CEP290mutation) • UMMSsponsoredresearchongoing+

STGD1“minigene”(ABCA4mutation) • UMMSsponsoredresearchongoing+

Therap

eutics

Gene

The

rapy

*FirstZimura trialforthisindication

Research/Pre-clinical

+ Optiontoin-licenseresultingIP

PipelineStrategy:BuildSustainableLong-termGrowth

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• Majormarketopportunity– Unmetmedicalneed• Anti-VEGFmonotherapy– Showntoreachaceilingeffect– Majorityofpatientsdonotreachavisualacuityof20/40orbetter– Intherealworldmostpatientslosevisionovertime– Patientsmaydevelopgeographicatrophy

• Roleofanti-VEGFincomplementactivationandatrophy– VEGFincreasesComplementFactorH(CFH)– CFHdecreasescomplementactivation– Anti-VEGFincreasescomplementactivation

• AddingZimuratoanti-VEGFtherapymayimprovetheefficacyandsafetySources:NEnglJMed2011;364:1897-908.NEnglJMed2006;355:1419-31. Ophthalmology2013;120:2292-2299.Ophthalmology2014;121:1092-101.JClin Invest.2017;127(1):199-214. Ophthalmology2015;122:809-816.Ophthalmology2016;123:1751-1761.

WetAMD:Zimura inCombinationwithAnti-VEGF

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WetAMD:Zimura Phase1/2a– Completed*

*Uncontrolledsafetytrial;smallsamplesize;subgroupanalysis

46% 47%

60%

0%

15%

30%

45%

60%

0.3mg 1.0mg 2.0mgn=13 n=15 n=15

≥3-ETDRSLinesVisualGainatWeek24

%Patients

• Included:− Treatment-naïvepatients− AllCNVsubtypes− Patientsreceivingsixmonthly

dosesofZimuraincombinationwithLucentis®0.5mg

• Safety:− Alldoseswelltolerated;no

safetyconcernswereidentified

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• Phase2aopen-labelclinicaltrial

• N=64subjectsenrolled

• Objectives:– ToassessthesafetyofintravitrealZimuraadministeredincombinationwithLucentis®0.5mgintreatmentnaiv̈esubjectswithwetAMD

– Doseranging– ValidateresultsfrompreviouslycompletedPhase1/2a

• Duration:6months

• Top-linedataexpectedbytheendof2018

WetAMD:Zimura Phase2a– Ongoing

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• Majormarketopportunity– Unmetmedicalneed– NoFDA/EMAapprovedtreatmentoptions

• RoleofcomplementindryAMD– GeneticlinkbetweencomplementandAMD– Withaging,complementdepositionincreasesandleadstotheformationofinflammasomesandaccumulationofMembraneAttackComplex(MAC)

– InflammasomeandMACaccumulationleadtoretinalpigmentepithelial(RPE)celldeathandlossofvision

Sources:TheJournalofBiologicalChemistryVol.290,NO.52,pp.31189–31198,December25,2015.InvestOphthalmol VisSci.2013;54:110–120.JImmunol.2015;195:3382-3389.Med Sci Monit,2010;16(1):BR17-23.AmJOphthalmol 2002;134:411–431.Proc Natl Acad Sci USA.2005,102(20),7053-7054.Science.2005Apr 15;308(5720):385-389;419-421;421-424.

GeographicAtrophySecondarytoDryAMD

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• Phase2b,randomized,double-masked,sham-controlledclinicaltrial• Cohorts:− Zimura:3doselevels− Sham

• 286subjectsenrolled;monthlystudytreatment(ZimuraorSham)for18months

• PrimaryEfficacyEndpoint− MeanrateofchangeinGAover12monthsmeasuredbyfundusautofluorescence(FAF)atthreetimepoints

• Top-linedataexpectedin4Q2019

GeographicAtrophy:Zimura Phase2b- Ongoing

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• Orphandisease– Highunmetmedicalneed– NoFDAorEMAapprovedtreatmentavailable

• ProgressivedamagetothemaculaandretinacausedbymutationsintheABCA4 gene

• ABCA4genemakesaproteinthatnormallyhelpsclearawayvisualcyclebyproductsinsideretinalcells

• Lackofthisproteinleadstotheaccumulationofwasteandcomplementactivationleadingtoretinalcelldeathandlossofvision

Sources:TheJournalofBiologicalChemistry.2011;286(21):18593–18601.ProcNatlAcadSciUSA.2017;114(15):3987-3992.InvestOphthalmolVisSci.2013;54:2669-2677.

AutosomalRecessiveStargardt Disease(STDG1)

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• Phase2bClinicalTrial– Randomized,doublemasked,shamcontrolledclinicaltrial– Twoarms:§ Zimura§ Sham

– N=~120subjects– Durationoftreatment:18months– PrimaryEndpoint:Meanrateofchangeintheareaofellipsoidzonedefectmeasuredbyen faceSD-OCT

– Top-linedataexpectedin2020• FoundationFightingBlindness– AccesstoFFB’spubliclyavailableProgStarnaturalhistorystudy– Patientregistryaccesstofacilitaterecruitment

Stargardt Disease:Zimura Phase2b– Ongoing

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• Manyocularorphanindicationsareduetogeneticdefects

• Potentialtocurediseaseswithsignificantunmetmedicalneed

• Eyeisanidealtargetforgenetherapy:– Localizeddelivery,minimizingsystemicexposure– Immuneprivileged– Depthofmonogenicdiseasecharacterization– Relativelyeasyaccesstopathology

• Positiveimplicationsforpatientsandhealthcareproviders

KeyRationaleforOcularGeneTherapyStrategy

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Rhodopsin-MediatedAutosomalDominantRetinitisPigmentosa

• Retinitispigmentosa (RP):mostprevalentinheritedretinaldystrophy

• Bilateraldegenerationofrodandconephotoreceptorsthatultimatelyleadstonightblindnessandprogressivevisualimpairment

• adRP:Themostcommonautosomaldominantretinaldisease

• Morethan150identifiedrhodopsingene(RHO)mutationsSource:ProgRetinEyeRes2018;62:1-23.

RhodopsinMolecule

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adRP:Phase1/2ClinicalTrialPlannedtoInitiatein2020

• MutationindependentstrategywithsingleAAVvectortechnology– Silences/knocksoutmutatedtoxicrhodopsinprotein– Produceshealthywildtyperhodopsinprotein

• Proof-of-conceptinanimalmodels(canineandmouse)– Preservationofretinalanatomyandfunction

• ClearpathtoINDsubmission– INDenablingandnaturalhistorystudiesplanned

ProcNatlAcad SciUSA.2018Aug20.doi:10.1073/pnas.1805055115.[Epub aheadofprint].HUMANGENETHERAPY23:356–366(April2012).

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• Extensiveexperiencewithintraocularapplication• Welldocumentedsafetyprofile• Tropismforretinaltissue• Limitedpackagingcapacityof<5kb− EngineerAAV-amenablegenesthatencodethefunctionallyoptimized

proteins

AAVVectorsareAppealingforOcularGeneTherapy

Minigene Therapy

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• Minigene Strategy– Leber CongenitalAmaurosis(CEP290)§ CEP290mutations:oneofthemostcommoncausesofLCA§ Earlyonsetvisionloss

– StargardtDisease§ CausedbymutationsintheABCA4 gene§ Progressivedamagetothemaculaandretina

• NovelGeneDeliveryMethods

AAVVectorTechnology

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• UpcomingZimura DataPoints– WetAMDin2018– DryAMD(GA)in2019– Stargardt in2020

• RHO-adRP ClinicalTrialExpectedtoInitiatein2020

• ContinueBusinessDevelopmentActivitiestoExpandPortfolio

• StrongCashPositiontoDriveGrowth– $146millionincashandcashequivalents*

ValueCreation:BuildingaLeadingRetinaCompany

*AsofJune30,2018