12-3-08 Investor Presentation (Final)

8/14/2019 12-3-08 Investor Presentation (Final)

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Athersys,Inc.


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Thestatementsanddiscussionscontainedinthispresentationthatarenothistoricalfactsconstitute

forwardlooking

statements,

which

can

be

identified

by

the

use

of

forward

looking

words

such

as

believes, expects, may, intends, anticipates, plans, estimates andanalogousorsimilar

expressionsintendedtoidentifyforwardlookingstatements.Theseforwardlookingstatementsand

estimatesastofutureperformance,estimatesastofuturevaluationsandotherstatementscontained

hereinregardingmattersthatarenothistoricalfacts,areonly predictions,andthatactualeventsor

results

may

differ

materially.

We

cannot

assure

or

guarantee

you that

any

future

results

described

in

thispresentationwillbeachieved,andactualresultscouldvarymateriallyfromthosereflectedinsuch

forwardlookingstatements.

Information contained in this presentation has been compiled from sources believed to be credible

and reliable. However, we cannot guarantee such credibility and reliability. The forecasts and

projectionsof

events

contained

herein

are

based

upon

subjective valuations,

analyses

and

personal

opinions.

This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any

securities. Such an offer or solicitation, if made, will only be made pursuant to an offering

memorandumanddefinitivesubscriptiondocuments.

ForwardLookingStatements

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CompanyHighlights

Focusonbiologics(MultiStem )andpharmaceuticals(forCNS/metabolic

relatedindicationsincludingobesity,cognitionandothers)

HighlystandardizedOfftheshelf celltherapyproduct,producedatscale

Administeredwithouttissuematchingorimmunesuppression

Multiplediseaseindicationsindevelopment multiplemechanismsofbenefit

Frost&SullivanProductInnovationoftheYearAward 10/29/08

NASDAQ:ATHX

$65MMfinancingcompletedinJune07

Emergingclinicalportfolioofbestinclass productcandidatesandtechnologies

Multipleclinicalstageprogramsindevelopment,strongpreclinicalpipeline

MultipleclinicaltrialsinitiatedwithMultiStem

Publiccompanywithstrongcashposition

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BusinessStrategy

Maintainleanoperationalinfrastructure/modestcoreburn

Costeffective

portfolio

diversification

+focused

core

competencies

Reducesriskanddevelopmentcost

Leverageprior

knowledge,

validation,

development

efforts

of

others

to

produceabetter,saferand/ormoreconvenientproduct

Multiplepotentialadvantagestobeingbestbutnotfirst incertainareas(but

alsoleveragingearlymover opportunityinareaswhereitmakessense)

Advanceprogramsasresourcesallow

Evaluatepartneringopportunitiesasweadvance

Developaportfolioofpotentialofpotentialbestinclassopportunities

UsingaFastFollower strategyinmultipleareas,EarlyMover inothers

Portfoliobasedapproachenablesdevelopment&partneringflexibility

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ObesityProgram

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ObesityMarketOpportunity

ClinicalLandscape

TherapeuticLandscape

Growing,globalhealthepidemiccontributingtoheartdisease, diabetes,cancerandstroke

Estimated30%ofAmericansareclinicallyobese(BMI> 30);anadditional~30%areoverweight(BMI> 25)

EconomiccostinU.S.aloneisestimatedat$117billionannually

Trueblockbusterpotentialforsafeandeffectivetherapies

Increasingrecognitionofobesityasseriousmedicalcondition

Nohighlyeffective&safedrugtherapiescurrentlyonmarket fewinclinicaltrials,recent

additionalattrition

due

to

demise of

CB

1antagonist

class

Severaltargetsarewellknownbuthavenotbeeneffectivelyexploitedtodate

Largepotentialmarket,patientvariability(efficacyandtolerability)createsroomfor

multipleplayersandMOAs

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ObesityProgram Overviewof5HT2cAgonists

5HT2c(serotonin)receptoragonistssuppressappetite&causeweightloss

Portfolioofpotentandselectivecompoundsestablished

Mechanismextensivelyvalidatedinhumans(e.g.fenfluramine,dexfenfluramine

recognizedashighlyeffectiveweightlossagents)but

Thesenon

selective

agents

also

activate

the

5HT2b

receptor

in

the

heart

and

cause

cardiovasculartoxicity(valvular hypertrophy=valvular regurgitation/heartmurmur)

Selective5HT2cagonists(i.e.thatdonotstimulate5HT2b)believedtobesafe

Selectivityrelativeto5HT2aimportanttolimitingCNSrelated sideeffects

ATHX105hasbeenthelead

MultiplePhaseItrialscompletedinU.K.(goodsafety&tolerabilityprofileobserved)

Excellentregionalabsorptionseeninrecentclinicalstudy(importantfordevelopmentof

modifiedreleaseformulation)

Currentlyonpartialclinicalhold havemetwithFDA,resolvedseveralissues,but

significantissueremains couldresultinsuspensionorterminationoffurtherdevelopment

Intendtoprovidefurtherupdateonprogramthisquarterafter completionofongoing

work,analysisofresultsanddialoguewithFDA

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Cognition&Wakefulness H3AntagonistProgram

HistamineH3ReceptorExtensivelyStudied MultiplePotentialApplications

Highqualityportfoliooftherapeuticcompoundsestablished

H3

Receptor

Antagonists

/

Inverse

Agonists

result

in

elevated

levels

of

histamine

in

certainregionsofthebraindirectlyaffectingcognitivetone

Compoundsimprovewakefulness(e.g.Narcolepsy,EDS)andcognition(e.g.ADHD,

Alzheimers)

Mayalso

have

relevance

in

other

indications

(e.g.

obesity,

neuropathic

pain)

Multiplecompoundscurrentlyunderevaluationinanimaltox,efficacystudies

Potent,highlyselectivecompoundsdevelopedbyATHX

Intendtoselectaclinicalcandidateandoneormorebackupcompoundsthis

quarter(pendingsuccessfulcompletionofongoingstudies)

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MultiStem:Biologic

ProductPlatform

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HistoricalLimitationstoStemCellTherapy

RequirementforcloseDonor Recipienttissuematching

Safety

Necessarytoavoidtransplantrejection

AlsoneededtoreduceincidenceofGraftvs.HostDisease

Onedonorforeachrecipient logisticallydifficultandverycostly

Biologicallimitationsofmostcellspreventlargescaleproduction

Mostcell

types

can

produce

limited

repertoire

of

more

differentiated

cells

Goalhasbeentoreplacelostordamagedcells(e.g.HSCtransplantation)

Rejection,GVHD,EctopicTissue,Teratoma /Tumorformation

Mechanisticfocushasbeenprimarilycell/tissuereplacement

Lackofabilitytoscaleproductionofcells

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November2008 PfizerannounceslaunchofReGenerative Medicine

Centers

$100million

program

to

develop

therapies,

focused

in

Cambridge

UK

(brain

/sensory)andCambridgeMA(heartdisease/diabetes)

November2008 Genzyme andOsirisannouncepartnershipto

commercializeProchymal andChondrogen (MSC)

$130million

upfront,

$1.25

billion

in

potential

milestones

OsiristocommercializeinU.S.;Genzyme inRoW

July2008 GSKannouncescollaborationwithHarvardStemCell

Institute

$25millionresearchpartnership

June2008 PfizerannouncesinvestmentinEyeCyte

Treatmentofeyediseases(e.g.,diabetesretinopathy)withadultstemcell(EPC)

2008 PharmaBiotechArrivingtoParty

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MultiStem: BestinClassCellTherapyProduct

Offtheshelf administration

LeadingIPpositionforpluripotent,multifunctionalnonembryonicstemcells

Notissuematchingneeded

Non

immunogenic

No

immunosuppression required

Bankedproduct,highlycharacterized

Largescaleproduction/yield(100kstomillionsofdosespossiblefromasingledonor)

Dynamicallyresponsivebiologictherapy=adrugliketherapy

Therapeuticeffectprimarilyfactormediated:antiinflammatory/immunomodulatory,

cytoprotective,trophic &

growth

factors,

angiogenic /

vasculogenic

Directcellreplacementplaysaminorrole

Multiplepotentialmechanismsoftherapeuticbenefit

Welldefined,FDAapprovedmanufacturingprocessinplace(withLonza)

MultipleINDs advanced

in

efficient,

cost

effective

manner 12


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OverviewofMultiStem ProductionProcess

LotRelease&ProductCharacterization

Testing

Sterility

Potency

PurityandViability

StableCytogenetics

Absenceoftumorigenic potentialinvivo

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MultiStem:AdditionalSafetyStudies

GLPToxicologyandClinicalPathology(2week,4week) Studiesindicatenoevidenceofacutetoxicityorabnormalclinicalpathology

GeneticStability

and

Tumorigenicity Testing

Karyotypic stability

ClinicalproducttestedinstandardNudemousetumormodels(bothi.v.ands.c.)

LongTermGLPHistopathologyAnalysis(oneyearforstroke) Extensive

histopathology

analysis

of

animals

receiving

clinical

grade

MultiStem

indicatesnoevidenceoftumorigenicity orectopictissueafteroneyear

Nootherabnormalitiesorotheradverseeventsnoted

ImmuneSensitizationAnalysis

Singleor

repeat

administration

(5x)

of

MultiStem does

not

cause

immune

sensitizationorabnormalclinicalpathology

GeneExpression,ProteinExpressionandSNPArrayAnalysis Noevidenceofvariabilitybetweenworkingcellbanksandproductionrunsafter

significantexpansion

of

clinical

grade

cellular

product 14


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MultiStem:MultiplePotentialMechanismsofBenefit

OPEN Phase I Trial for HSC/BMT Support& GVHD Prophylaxis

OPEN Phase I Trial for AMI

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16

FocusedProductDevelopmentApproach

Treatment

Acute/Ischemic

Injury

ImmuneSystem

Modulation

o AcuteMyocardialInfarction

(Ph1initiated)

o IschemicStroke

o HSC/BoneMarrowTransplant Support/

GVHD(Ph

1initiated)

o Chronicischemia/CHF

o Peripheralvasculardisease

o Traumaticbraininjury&related

o OtherNeurological

Indications

o Otherischemicinjury(e.g.,kidney)

o MultipleSclerosis

o Diabetes(type1)

o Transplantation

o Inflammatorybowel

disease

o Otherautoimmune

disorders

MultiStem

Otherthemes,e.g.,proteindeficiencies,

bonegrowth

Nextgeneration

opportunities

o OtherNeurologicalIndications

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AcceleratingMultiStem ProofofConceptPath

Proofofconceptwithcelltherapyproducts

Standardizedandscalableproductmanufacturing

Basicsafety inhumanswithindesireddoserangesanddeliveryapproaches

PhaseIstudies

(with

potential

for

efficacy

signals)

Efficacyinhumans

FocusinneartermonPhaseI/IIstudiesinindicationswithdiscreetendpoints/readoutsovershort showingofdesiredbiologicalactivityandbenefit

Furtherelucidationofmechanismsofbenefit(fromanimalmodels,invitro)

support

clinicalfindings

Fastestpathlikelyinfusedproductinimmunomodulatory area

LeverageINDBB13507(EvaluationofMTDofSingleandRepeatedAdministrationofAllogeneic MultiStem inPatientswithAL,CMandMyelodysplasia)

Treatmentof

(steroid

refractory,

or

acute)

GvHD

Basically,samepatientpopulationwithwelldefinedshortertermendpoints;samesites

Otherimmunomodulation indication(s): exploitsametherapeuticpathways,andconditionswithsimilartreatmentapproaches

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MultiStem for

Acute

MyocardialInfarction

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MultiStem: AcuteMyocardialInfarction

AMIremainsamajorareaofneedforimprovedtherapies

INDapproved,clinicaltrialinitiatedwithcodevelopmentpartner(Angiotech)

865,000heartattacksannuallyintheU.S.

156,000deaths

SignificantincidenceofprogressiontoCHF

Reducesinflammationrelateddamageandpromotesrevascularization

Alsoexploringadministrationviai.v.

MultiStem demonstratedsafeandeffectiveinmultiplepreclinicalmodels

Local(catheter)deliveryofMultiStem followingheartattack

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InnovativeApproach:StandardizedProduct+EfficientLocalDelivery

Standardizedproduct

(administered

without

matching

or

immunosuppressive

agents)

Reducesinflammationrelateddamageandpromotesrevascularization

Administrationof

cell

product

into

perivascular region

Relativeeaseofuse,comparabletostandardangioplasty

Athersys andpartner,

Angiotech Pharmaceuticals

ClevelandClinicFoundation,HenryFordHealthSystem,UniversityofMichigan&

others

Administrationofbonemarrowderived,allogeneic MultiStem cells topatients

Targeted,localdeliveryincoronaryarterieswithtransarterial catheter

Strongpartnersandleadinginvestigationalsites

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Allogeneic MultiStem DeliversFunctionalImprovementinPig

ModelsofCardiovascularIschemia

ConsistentimprovementacrossmultiplefunctionalparameterswithsingledoseadministeredpostMI

Noobservedsafetyissues

20

2530

35

40

45

50

55

60

Baseline 1 Wk post-MI 4 Wk post MI

Ejection

Fraction

%

P-value < .02p-value < .005

Transientischemia,catheterdelivery

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Transarterial CatheterDeliveryApproach

MercatorMedSystems,510(k)approvedMicroSyringe InfusionCatheter

Sitespecificdeliveryintoperivascular spaceandadventitia

Retaingreaternumberofcellsat/nearinjurysite(reducewashawayofcellsintobloodstream)

Relativeeaseofuse

Goodcellviability,efficienteaseofuse

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Strategy

Objectives

PhaseIStudy,openlabel,doseescalation

PhaseIClinicalProtocolSummary AMI

STEMI,LVEFbetween3045%

Administrationof

MultiStem in

coronary

artery

(via

transarterial catheter)

deliveredonday25afterAcuteMI

Threedosegroups(6patientseach)plus10patientregistrycohort

Multiplesites,largelyregional

Primaryendpoints:safety (arrhythmias,acutetoxicity,hospitalization,death,

mechanicalcomplication)

Secondaryendpoints:functionalitymeasures(e.g.LVEF)

Providesafetyfoundationandinformationtoenabledesignofmeaningful

PhaseIIexploratorystudy(e.g.,doselevels,deliverytiming)

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DeliveryofMultiStem inAMIpatient

5sec 30

sec 60

sec

Delivery, retention of cellsin area of ischemic damage

Vessel patencyRapid, efficient procedureWell tolerated

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MultiStem forSupport

of

HematologicalStemCellTransplants

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MultiStem: Transplantation(GvHD)

Frequent,potentiallylifethreateningconsequenceofHSC/BMtransplants

INDapproved,clinicaltrialinitiated

Clearneedforimprovedtreatmentsbeyondbroadimmunosuppression

Limitedtreatmentoptionsforcomplications(e.g.,GvHD)

Otherproblemsassociatedwithconditioningregimen(e.g.,GIfunction)

ReductionofGvHD impactandpromotionoftissueregenerationandengraftment

PotentialforGvHD intervention

MultiStem demonstratedsafeandeffectiveinpreclinicalmodels

IVdeliveryofMultiStem inconjunctionwithHSC/BMtransplant

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MultiStem ImmunoPrivilegedInVitro

Mixture

Donor 1 Cells(Rare alloreactive T-

cells in red)

Mixed Lymphocyte Reaction

Donor 2 Cells

Recognition of allogeneic cellscauses T-cell activation and

proliferation

Proliferation measurable byincrease DNA synthesis Self to self

Allogeneic T-cell controls

T-cells dont reactto MultiStem (MAPC)

MultiStem does not elicit In VitroT-Cell Response in MLR Studies

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MultiStem Immunosuppress Alloreactive TCells

MAPC(MultiStem)

SuppressesImmune

Response

MultiStem (likeMSC)Exhibits

ImmunosuppressiveEffectsOnMLR

(human)

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

180,000

R (Lewis)+ S (DA) R (Lewis) No responder or stimulator

3H-thymidin

ecounts

None 0.03x10 5

0.06x10 5 0.125x10 5

0.25x10 5 0.5x10 5

1x10 5 2x10 5

DoseDependentSuppressionofAllogeneic TCell

ResponseinMLR(Lewisrat)

DoseDependent

Effect

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MultiStem ProvidesSurvivalAdvantageinRatAcuteGvHD Model

Ratssublethally irradiated

and

injected

withbonemarrowcellsandTcellsfromdifferentratstrain creatingGraftvs.Hostimmuneresponse

MultiStem administeredI.V.atday1,

orat

days

1and

8

MultiStem providessignificantsurvival

benefitversus

animals

receiving

no

treatment

BenefitsobservableforotherGvHDindicators(bodyweight,activity,posture,furtexture,skin)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34

Days

Survival

No treatment

Treatment, day 1

Treatment days 1+8

Significant survival advantage in MultiStem treated animals

Design

Results

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GutPathologyinRatAcuteGVHDModel

GVHD,PBSControl

Treated

GVHD,MultiStem

Treated

Day15Pathology,MultitreatmentGroup

Substantiallyless

gastrointestinal

damage

inMultiStemtreated

animals

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Objectives

Strategy

PhaseIstudy,openlabel,doseescalation

PhaseIClinicalProtocolSummary Transplantation/GvHD

Patients(leukemia,myelodysplasia)undergoingPBSC/bonemarrowtransplantation

Administrationof

MultiStem intravenously

Twotreatmentarms:Singledosecoadministeredwithtransplant,multipledoses

administeredoverfirst30days

Continualreassessmentmethodology

Primaryendpoints:safety:maximumtolerateddosebasedoncompositeofDLTs and

AEs through30days

Secondaryendpoints:incidenceandseverityofGVHD,survival,infection

Providesafetyfoundationtoallowfor(a)prophylactictreatmentandinterventionfor

GVHD,and(b)singleandmultipledosetreatmentapproaches

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Multipleindicationspossible

Treatingemergentorchronicautoimmunedisease

OpportunitiesinOtherAutoimmuneDisease

Immunomodulatory activityofMultiStem forGVHDismechanisticallysimilar

tobiological

conditions

for

other

autoimmune

conditions

Rapidclinicalentryispossible(leveragingoffofexistingpreclinicaland

clinicaldata)

Manufacturingcapabilityalreadyinplace

Widerangeofautoimmuneconditionswithunmetmedicalneedaspotential

therapeutictargetsforMultiStem

I.V.delivery

Otherpotentialbenefitstohelpaddresstissuedamage

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MultiStem forIschemic

Stroke

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MultiStem: IschemicStroke

SubstantialunmetneedinthetreatmentofIschemicStroke

INDfilingplannedfor2H,2008

Over700,000strokesannuallyinU.S.,and~80%+ischemicstrokes

Substantialfunctionallossandrehabilitationandfollowupcarecosts

Limitedtreatmentoptions,tPA mustbeadministeredwithin3 4.5hrsofstroke

Broadpotentialtreatmentwindow

Benefittrophicfactormediated:reduceinflammation,stimulaterevascularization,

override processes of cell / tissue decline & contribute to tissue regeneration

MultiStem demonstratedsafe

and

effective

in

pre

clinical

models

IVdeliveryofMultiStem 48hours(+/)followingIschemicStroke

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AnimalModelsofCerebralIschemia

36

MCA Occlusion

MCA Ligation

P Cli i l E i l A h


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Experimentalapproach

1. Immunosuppression (+/)withallo/

xenogeneic cells,intracranialdelivery

2. Routeof

administration:

viability

of

IV

delivery

3. Deliverywindow:17dayspoststroke

4. Doseescalation

PreClinicalExperimentalApproach

37

Keyresults

Immunosuppression notrequiredforsafeimprovementtoneurological

function

Significantfunctionalimprovement(locomoter,neurological)statisticallyovercontrol

Comparableimprovementinlocomotor orneurologicalfunctionobservedamonganimalsreceivingcellsat1,2or7

days

DoseresponseobservedwithIVinfusedcells,asmeasuredbyneurologicalimprovement

Engraftedcellsdisplayneuronalmarkersinneonatalmodel

Noabnormaltissuesorabnormalpathologyobservedin

animalskept

on

study

for

1year

post

cell

transplantation

Single Dose of Human MultiStem Provides Robust Durable Improvement


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SingleDoseofHumanMultiStem ProvidesRobust,DurableImprovement

inRodentModelofIschemicStroke

0.4 units

1 units

2 units

4 units10 units

20 units

10 units non-viable cells (control)

Dose response Therapeutic benefitproportional to dosedelivered

Treatment timing

Improvementwhether delivery atday 1, 2 or 7

Bederson Composite Score of Neurological Function,IV-deliveryof MultiStem day 2 post-stroke

Baseline

Post-

Stroke

Day14

Day28

Day42

Day56

MeanNeu

rologicalScore

1.5

2.5

0

0.5

1

2

3

38

M ltiSt P Hi hli ht


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MultiStem ProgramHighlights

BroadMultiStem productplatformforcellbasedtherapyinitiatingclinicaltrials

Potentialforbroaddevelopmentprogram

Standardized,offtheshelfproduct(aproduct,notaprocedure)

Firsttruly

scalable

manufacturing

platform

for

cell

therapy

StrongIPposition

Ischemicinjury:AMI(possiblyischemicstroke)

Immunomodulation andtissuedamage:BoneMarrow/HSCTransplantation/GvHD

Otherneurologicalindications,autoimmunedisease,otherareas

Singlemasterfile approach=highlyefficientdevelopment

Progresswillbebasedonvalidationinappropriatemodels,collaborationwithexperts

2008Focus:Initiatingclinicaldevelopmentactivities

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Financials&Milestones

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Athersys Key Milestones


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Athersys KeyMilestones

BeginATHX105PhaseIstudy

INDapprovalforMultiStem HSCtransplantsupport/GvHD

INDapprovalforMultiStem AMI

NASDAQlistingandshareregistration

EvaluateH3antagonistcompoundsformultipleindications

Review/evaluateATHX105PhaseItoplineresults

SubmitATHX105PhaseIIplantoFDA

CompleteadditionalATHX105clinicalstudiesre:safety,regionaldrugabsorption

LaunchMultiStem GVHD/OncologySupportPhaseIclinicaltrial LaunchMultiStem AMIPhaseIclinicaltrial

ResolvePartialClinicalHoldwithFDA

CompletefurtherpreclinicalstudiesforH3antagonistprogram/selectcandidate

INDApprovalforMultiStem Stroke(Initiatetrialdependingonresourceavailability)

2007

2008

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Athersys,

Inc.

12-3-08 Investor Presentation (Final)

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Transcript of 12-3-08 Investor Presentation (Final)