NewResearchValidatesbothSingleAgentandSynergisticAnticancerActivity
forAraviveBiologics’Anti-AXLCandidateinMultipleTumorTypes
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JournalofCancerInvestigationarticleshowsthatinpreclinicalstudiesAravive-S6achievesantitumoreffectsthroughhighlyselective,potentinhibitionofAXL-signaling,resultinginDNA
replicationstress
PreclinicalstudiesshowlackoftoxicityandsuperioranticanceractivityforAravive-S6against
AMLandadvancedovarian,pancreaticandbreasttumors,bothasasingleagentandinsynergy
withcytotoxicdrugs,comparedtocurrentsmallmoleculeAXL-inhibitors
MechanismofactionsuggestsbroadutilityofcombiningAravive-S6withotheranticancerdrugs
thatperturbDNAreplicationandrepair,includingPARPinhibitors
Houston,TX(November29,2016):Aravive-S6,anoveltherapeuticcandidateunderdevelopmentby
AraviveBiologics,Inc.showsstrong,highlyselectivepreclinicalactivityagainstmultipleadvancedforms
ofcancerasbothasingleagentandinsynergywithotherchemotherapeuticdrugs,accordingtonew
researchpublishedtodayintheJournalofCancerInvestigation.Aravive-S6isattributedwithselectively
inhibitingtheAXL-signalingpathwaywhichactsasa“survivalswitch”thatscientistsbelievepromotes
tumorgrowthandmetastasis,andresistancetocommonchemotherapeuticagents.Inaddition,AXLinhibitionhasbeenattributedwithcausingDNAreplicationstressandperturbsDNAreplicationand
repair,leadingtoenhancedtumorcelldeath.Thismechanismofactionsuggeststhatthecombination
ofAravive-S6withotheragentsthataffectDNAreplicationandrepair,includingPARPinhibitors,may
offeranexcitingnewavenueforimprovingcancertherapy.
Theco-seniorauthoroftheJCIresearchpublication,entitled“Augmentingtheefficacyof
chemotherapiesbyinhibitingtheGas6/AXLpathway,”isAmatoJ.Giaccia,Ph.D.,scientificfounderand
actingchiefscientificofficerofAraviveBiologics,whichholdsanexclusivelicensefromStanford
UniversitytoAravive-S6andtheresearchfindingsdescribedinJCIpaper.Hecollaboratedonthework
withresearchersatStanford.
“ThisresearchaddstoourunderstandingofAXLasananticancertargetintwocriticalways,”saidDr.
Giaccia.“First,weprovidesupportthatAravive-S6isaveryselectiveandpotentbiologicthatshows
evidenceofsuperiorityoverthecurrentpipelineofanti-AXLcompounds.Moreimportantly,by
demonstratingthatinhibitingAXLaddstothereplicativestressfacedbycancercells,wesuggestaway
toimprovetheefficacyandtherapeuticindexofbothstandardcytotoxicchemotherapiesandother
agentsthatperturbDNAreplicationandrepair,suchasPARPinhibitors.”
TargetingAXLSignalingtoBlockDiseaseProgression
Asunderstandingofthemolecularbasisofcancerhasimproved,researchershaveidentifiedanumber
ofsignalingpathwaysresponsiblefordrivingdiseaseprogression.Inmanycases,however,thegenetic
instabilityandhighmutationratesthatoccurincancer,coupledwiththeredundancyoftenbuiltinto
biologicalsystems,havelimitedtheusefulnessoftherapiesdirectedagainstsuchtargets.TheAXL
receptor,incontrast,appearsnottobecomemutatedincancer,andinfactbecomeselevatedastumors
evolveandexperienceincreasedDNAdamage.AXLsignaling,triggeredbythebindingofGas6toAXL,
drivestumorprogressionandmetastasis,aswellastheabilityoftumorstobecomeresistanttomany
chemotherapeuticdrugs.Inseveraltumorstypes,includingacutemyeloidleukemia(AML)and
advancedformsofovarian,pancreaticandbreastcancers,targetingAXLhasbeenshowntohave
beneficialanticancereffects.However,drugcandidatestargetingAXL--mostlysmallmoleculekinase
inhibitors(TKIs)--haveshowneitherlimitedefficacyand/orconsiderabletoxicityinstudiestodate.
Inthepublishedstudies,theresearcherstestedanovelfusionprotein,Aravive-S6,whichhasbeen
designedasa“decoy”receptortostronglybindGas6withhighlevels(sub-picomolar)ofaffinity,and
thuspreventthetriggeringoftheAXLpathway.Theresearchersshowedtheabilityofthedecoyalone
toinducecellkillinginAMLcellsandsignificantlyinhibitdiseaseprogressioninaggressivemodelsof
ovarian,pancreaticandbreastcancer.Inthesepreclinicalresearchstudies,whentheauthorsdirectly
comparedthedecoymoleculetothemostadvancedanti-AXLTKIsintheclinic,Aravive-S6achieved
superioranti-tumorefficacywhiledisplayingnosignsofpotentialtoxicity.MoreoverwhenAravive-S6
wascombinedwithstandardchemotherapeuticdrugs,evengreateranticancerefficacywasseenin
multipletumormodels.Moreover,inapreclinicalmodelofhumanadvancedovariancancer,the
treatmentcombinationisattributedwithreducingtumorburdenbymorethan99%,andthreeoutof10
treatedanimalshadnoevidenceofdiseaseaftertreatment.
Inaresultthatwassurprisingtotheinvestigators,theyfoundevidencethatAXLsignalingprovidedcytoprotectionfortumorcellsandthelossofAXLsignalingledtoreplicativestressandtheactivationofthe
DNAdamageresponse.“DNAdamagingagentshavelongbeenusedtotakeadvantageofcancer’s
hyperproliferativestate,andwehaveshownthatmodulationoftheDNAdamageresponsebyinhibiting
AXLcanincreasethetherapeuticeffectsofthosedrugsbothinlaboratoryandanimalstudies,”saidDr.
Giaccia.“Ourresultssuggestthatanti-AXLtherapiessuchasAravive-S6canbebroadlyusedtoheighten
theeffectsofcytotoxicandotheragentsacrossabroadspectrumofcancers.Thisfindingisparticularly
excitingforthestrategyofcombiningAravive-S6withPARPinhibitors,whichalsoactbydisruptingDNA
replication.”
“Weareextremelyexcitedaboutthesefindings,whichsupportourongoingdevelopmenteffortswith
Aravive-S6inAMLandcertainaggressivesolidtumorswhereAXLisshowntoplayakeyroleindrug
resistanceandcancersurvival,”saidRayTabibiazar,M.D.,PresidentandChiefExecutiveOfficerof
AraviveBiologics.“WecontinuetoworktowardsenteringtheclinicwithagoaloffilingINDbyendof
2017.”
AboutAraviveBiologics,Inc.
AraviveBiologicsisaprivatelyheld,latepre-clinicalstagebiopharmaceuticalcompanydevelopingnovel,
highlyselectivecancertherapiesthattreatseriousmalignancieswhilesparingnormalhealthycells.The
company’s lead program is focused on the GAS6/AXL pathway, where activation appears to play a
critical role in multiple types of cancer malignancies by promoting tumor metastasis and cell survival.
Aravive Biologics has generated strong preclinical data for its lead drug candidate, Aravive-S6, in both
acutemyeloidleukemia(AML)andsolidtumorsincludingovarian,pancreatic,andbreastcancers.The
company is based in Houston, Texas, and receives support from the Cancer Prevention & Research
InstituteofTexas(CPRIT).Formoreinformation,pleasevisitourwebsiteathttp://www.aravive.com.
ForwardLookingStatement
This press release contains forward-looking statements. Forward-looking statements contained in this
pressreleaseinclude,withoutlimitation,statementsregardingthetimingoftheINDfiling,theexpected
role of the Aravive-S6 Fc-fusion protein in blocking the activation of the GAS6-AXL signaling pathway,
thetimingofcommencementofclinicalstudies,andintendeduseofAraviveBiologics’complementary
diagnostictooltoidentifypatientswithcancersexhibitingelevatedGAS6levels.Wordssuchas"may,"
“believe,”"will,""expect,""plan,""anticipate,""estimate,""intend"andsimilarexpressions(aswellas
other words or expressions referencing future events, conditions or circumstances) are intended to
identify forward-looking statements. These forward-looking statements are not guarantees of future
performance and involve a number of unknown risks, assumptions, uncertainties and factors that are
beyondAraviveBiologics'controlincludingtheabilityofAravive-S6toserveasadecoythatpreventsthe
binding of GAS6 to the AXL receptor on tumor cells and the ability of Aravive Biologics’ companion
diagnostic tool to identify patients with cancers exhibiting elevated GAS6 levels. All forward-looking
statements are based on Aravive Biologics' expectations and assumptions as of the date of this press
release.Actualresultsmaydiffermateriallyfromtheseforward-lookingstatements.Exceptasrequired
bylaw,AraviveBiologicsexpresslydisclaimsanyresponsibilitytoupdateanyforward-lookingstatement
containedherein,whetherasaresultofnewinformation,futureeventsorotherwise.
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Contacts:
DanielleMalloy
Director,CorporateOperations,AraviveBiologics,Inc.
[email protected]
JoanE.Kureczka
[email protected];
Ph:415-821-2413,Mob:415-690-0210