Dr.Dr.SvenRohmann/CBDO

TranslationalMedicineORYX

ORYX– Overview

2

Ø ORYXGmbH&Co.KG(ORYX)isaprivatelyheldcompanyfortranslationaloncologyfoundedin2007andlocatedinBaldham/Munich,Germany

Ø ORYXbridgesthegapfornewcancertherapiesbetweenleadingacademicresearchinstitutionsandthepharmaceuticalindustry

Ø ORYXistheexclusivelicenseeofthreepremiercancerimmunotherapysubstancesoftheGermanCancerResearchCenter (DKFZ)andtheUniversityofHeidelberg

Ø ORYXhassuccessfullydevelopedthesesubstancesinclinicalphaseI/IIa trials,hasobtainedcompellingsafetyandefficacydataintheseclinicaltrials,andisnowlookingintopartneringthesesubstancesforthepivotaltrials

ORYX– Pipeline

3

CancerImmunotherapy

Substances

ModeofAction

CurrentCancer

Indications

Pre-Clinical ClinicalDevelopment

MicOryx

VicOryx

ParvOryx

Syntheticframeshift

peptidesvaccine

Synthetichumancyclin-dependentKinaseinhibitorpeptidevaccine

Wild-type ratoncolyticvirus

Concurrentvaccination&chemotherapy

Colorectal

CervicalHead&Neck

GBM

PDAC

PhaseI/IIa completed

PhaseI/IIa completed

PhaseI/IIa completed

PhaseI/IIaongoing

PhaseI/IIacompleted

POC/Toxicology

PhaseI PhaseII PhaseIII

CompassionateUseProgramsGBM/CRC

Ø SeveralcancersarisefromthelackofDNAmismatchrepair(MMR),resultingintheaccumulationofsingledeletionsorinsertionsatcodingmicrosatellites(MSI-Hmutations)

Ø CancerswithMSI-Hmutationsinclude:• 10-15%ofcolorectalcancers• 20-25%ofendometrialcancers• 25-30%ofupperurinarytractcancers• 15-20%ofgastriccancers• 5-10%ofpancreaticcancers

Ø MSI-Hmutationsleadtotheexpressionofframeshiftpeptides(FSPs)

Ø FSPsaretumorspecificantigenswhichareconstantlyexpressed

Ø InpatientswithMSI-HcolorectalcanceranaturalhumoralandcellularimmuneresponseagainstFSPsisfound,whichdemonstratesthatFSPsarerecognizedbytheimmunesystemandcantriggeranimmuneresponse

MicOryx – Rationale

4

Results

PrimaryObjective: Safety• 22/22patients(100%)

SecondaryObjective: Efficacy• SpecificimmuneresponsesagainstFSPsin21/22patients(95,5%)

• StableDiseaseinstageIIIandIVpatients

5

Trialdesign

Singlecenter,twopartopenlabel,prospectivestudy• 1st part6patients,2nd part16patients(n=22)• UICCstageIII/IVMSI-Hcolorectalcancer

Totalof12s.c. applicationswiththreeFSPsonetime/weekforfourconsecutiveweeks,followedbyafourweekrestperiod(onecycle)foratotalofthreecycles

Monitoringoftoxicity,immuneresponse(includingDTH),andtumorresponse

SubcutaneousinjectionofFSPsandMontanide ISA51VGStudyWeek

1 2 34 9 10 1112 17181920 25

MicOryx 01– ClinicalPhaseI/IIa – completed

Ø Inmanysolidcancersthecyclin-dependentkinaseinhibitorp16INK4aisexpressed

Ø p16INK4a positivecancersinclude:• 20-30%ofbreastcancers• 60-70%ofsmallcelllungcancers• 90-100%ofHR-HPVassociatedcancers,e.g.

cervicalcancer,headandneckcancer,analandvulvarcancer,vaginalandpenilecancer

Ø Incancercells,p16INK4a isatumor antigenwhichisconstantlyexpressedasanearlyconsequenceofcelltransformation

Ø Innormalcells,p16INK4a israrelyexpressedandleadstoimmediatesenescence

Ø InpatientswithHR-HPVassociatedcancersanaturalhumoralandcellularimmuneresponseagainstp16INK4a canbefound,whichindicatesthatp16INK4aisrecognizedbytheimmunesystemandcantriggeranimmuneresponse

VicOryx – Rationale

6

VicOryx 01– ClinicalPhaseI/IIa - completed

7

Trialdesign

Singlecenter,twopartopenlabel,prospectivestudy• 1st part10patients,2nd part16patients(n=26)• UICCstageIII/IV,advancedHR-HPV- andp16INK4apositivecervix,vulvar,vaginal,penile,analorheadandneckcancer

Totalof12s.c. applicationswithaspecificp16INK4a peptideonetime/weekforfourconsecutiveweeks,followedbyafourweekrestperiod(onecycle)foratotalofthreecycles

Monitoringoftoxicity,immuneresponse(includingDTH),andtumorresponse

Subcutaneousinjectionofp16andMontanide ISA51VGStudyWeek

1 2 3 4 9 10 11 12 17181920 25

Results

PrimaryObjective: Safety• 26/26patients(100%)

SecondaryObjective: Efficacy• Specificimmuneresponsesagainstp16INK4a in18/26patients(69,2%)

• StableDiseaseinstageIIIandIVpatients

VicOryx 02– ClinicalPhaseI/IIa - completed

8

Trialdesign

Singlecenter,openlabel,prospectivestudy

• Onconcurrentcisplatin-basedchemotherapycombined withspecificp16INK4a peptidevaccination,10patients

• UICCstageIII/IV,advancedHR-HPV- andp16INK4apositivecervix,vulvar,vaginal,penile,analorheadandneckcancer

Totalof12s.c. applicationswithaspecificp16INK4apeptideonetime/weekforfourconsecutiveweeks,followedbyafourweekrestperiod(onecycle)foratotalofthreecycles• Vaccinationisappliedoneweekbeforetheinitiation

orcontinuationofcisplatin-basedchemotherapy

Results

PrimaryObjective:• Feasibilityofvaccinationduringchemotherapy

• Specificimmuneresponseagainstp16INK4a

SecondaryObjective:• Safety,PFS,OS• TumorresponseaccordingtoRECIST

Ø Combinedtherapyshowsexcellentsafetyandtolerability

ParvOryx – Synopsis

9

PotentialsCharacteristics

WildtypeDNAvirus

Excellentsafetyprofile

it.and/oriv.possible

Nopriorimmunityinhumans

Repeatedit.- and iv.- applicationpossible

Oncolysisandbystandereffect

• Passesbloodbrainbarrier• PotentialtobearmedwithtumourspecificsiRNAs

• Notpathogenicforhumans• Lysesonlytumourcells• Noeffectonnormaltissue

• Prolongedtherapeuticwindow

• Potentialforvaccination

• HighH-1PVsusceptibilityinmanycancers• Changeoftumormicroenvironment• Potentialforcombinedmodalitytreatment

• Potentialtolocalandsystemicadministration

VirusType

Safety

Application

Immunity

Booster

Efficacy

ParvOryx 01- ClinicalPhaseI/IIa - completed

Trialdesign

Singlecenter,openlabel,prospective,doseescalatingstudy• 1st group(it)12patients,2nd group(iv)6patients(n=18)• UICCStageIV

• progressiveprimaryorrecurrentglioblastomamultiforme

It:halfofthedoseinthetumor,halfofthedoseinthewalloftheresectioncavity

Iv:halfofthedosein5consecutiveinjections,halfofthedoseinthewalloftheresectioncavity

10

Results Immuneresponse

PrimaryObjective: Safety• 18/18patients(100%)

SecondaryObjective: Efficacy• PFS≥6month:33%/10% (1)

• OS≥6month:80%/40%(1)

Ø Strongcellularimmuneresponseagainstgliomaandviralproteins(bystandereffect)

(1)(www.ncbi.nlm.nih.gov/pubmed/17108063)

ParvOryx 02– ClinicalPhaseI/IIa - ongoing

Trialdesign

Singlecenter,openlabel,prospective,doseescalatingstudy,7Patients

UICCstageIVmetastaticinoperablepancreaticcancer

Ø iv.-administrationfollowedbyit.-administrationinsinglelivermetastases

Results

PrimaryObjective: Safety

SecondaryObjective:PFS,OSAnti-tumoreffects• Specificcellularandhumoralimmuneresponses

• Tumorinfiltration• Metastaticnecrosis• Virusactivityinthetumortissue

11

ParvOryx – CompassionateUsePrograms

12

ParvOryxandAvastin®

➡�

Tumorregressionin• 2/2recurrentGBMpatients

ParvOryxandICI*

Tumorregressionin• 1/1CRC• 1/1recurrentGBMpatient

➡�

ParvOryxICIandAvastin®

Tumorregressionin• 7/7 recurrentGBMpatients

➡�

*ICI:Immunecheckpointinhibitor

ParvOryx – Controlledadaptive4-ArmPhaseIIStudy

13

ParvOryx ivandAvastin®

ParvOryx ivandICI*

ParvOryx ivICIandAvastin®

➡�

*ICI:Immunecheckpointinhibitor

BestArm

ControlArm:CCNU

CCNU

4-armrun-in-study 2-armmainstudy

Disclaimer

14

ThisPresentationincludesandisbased,interalia,onforward-lookinginformationandstatementsthataresubjecttorisksanduncertaintiesthatcouldcauseactualresultstodiffer.ThesestatementsandthisPresentationarebasedoncurrentexpectations,estimatesandprojections,whichgenerallyareidentifiablebystatementscontainingwordssuchas”expects”,”believes”,”estimates”orsimilarexpressions.Importantfactorsthatcouldcauseactualresultstodiffermateriallyfromthoseexpectationsinclude,amongothers,generaleconomicandindustryconditionsinmarketswhichareexpectedtobemajormarketsforORYXproducts,aswellasrisksanduncertaintiesrelatedtoproductdevelopment,regulatoryapprovals,commercialpartnerships,theoutcomeofintellectualpropertyrightslitigationandthecompetitivesituation.

AlthoughORYXbelievesthatitsexpectationsandthePresentationarebaseduponreasonableassumptions,itcangivenoassurancethatthoseexpectationswillbeachievedorthattheactualresultswillbeassetoutinthePresentation.ORYXismakingnorepresentationorwarranty,expressedorimplied,astotheaccuracy,reliabilityorcompletenessofthePresentation,andneitherORYXnoranyofitsdirectors,officersoremployeeswillhaveanyliabilitytoyouoranyotherpersonsresultingfromyouruseoftheinformationcontainedherein.

Thispresentationwaspreparedforthe2016BIOInternationalConvention inSanFranciscoonJune6-9,2016.Theslidesshouldbereadandconsideredinconnectionwithotherinformationprovidedbythecompany.

Marktplatz 185598Baldham,Germany

ORYX– PartneringOpportunities

Phone: +49-8106-21311-0Fax: +49-8106-21311-66E-mail: info@oryx-medicine.com

ContactORYXGmbH&Co.KG

www.oryx-medicine.com