ONO PHARMACEUTICAL : Phase I/II Opdivo (nivolumab) Trial Shows Bristol-Myers Squibb’s PD-1 Immune Checkpoint Inhibitor is First to Demonstrate Anti-Tumor Activity In Patients With Hepatocellular Carcinoma(147KB)

June 2, 2015

(PRINCETON, NJ, May 29, 2015) - Bristol-Myers Squibb Company (NYSE: BMY) announced results from an interim analysis of CA209-040, a Phase I/II dose-ranging trial evaluating the safety and anti- tumor activity of Opdivo (nivolumab) in previously-treated patients with hepatocellular carcinoma (HCC) or advanced liver cancer. Initial findings demonstrated that the estimated survival rate in evaluable patients (n=47) was 62% at 12 months. Results also show the safety profile of Opdivo is generally consistent with that previously-reported for Opdivo in other tumor types.
Through the collaboration agreement entered into in September 2011 between ONO and BMS, ONO granted BMS exclusive rights to develop and commercialize Opdivo in the rest of the world, except in Japan, Korea and Taiwan where ONO had retained all rights to develop and commercialize the compound. In July 2014, ONO and BMS signed a new collaboration agreement in which the companies agreed to jointly develop and commercialize Opdivo, ipilimumab and three early-stage immunotherapies in Japan, South Korea and Taiwan.
In USA, Opdivo was approved under accelerated approval for the treatment of unresectable or
metastatic melanoma and disease progression following Yervoy and, if BRAF V600 mutation positive, a BRAF inhibitor in December 2014 and approved for the treatment of metastatic squamous NSCLC with progression on or after platinum-based chemotherapy in March 2015. Also, BMS has a robust clinical development program in a variety of tumor types overseas, including: Renal Cell Carcinoma (RCC), Head and Neck Cancer, Blood Cancer, Glioblastoma, Colorectal Cancer, Pancreatic Cancer, Gastric Cancer, Hepatocellular Carcinoma, Triple-Negative Breast Cancer, Small-Cell Lung Cancer, Bladder
Cancer. In Japan, ONO launched it for the treatment of unresectable melanoma in September 2014. Also, ONO is conducting clinical development programs including RCC, NSCLC, Head and Neck Cancer, Gastric Cancer, Esophageal Cancer, Hepatocellular Carcinoma and Hodgkin Lymphoma.
Attached from the following page is the press release made by BMS for your information.
Contact
ONO PHARMACEUTICAL CO., LTD. Corporate Communications public_relations@ono.co.jp

 Interim results show favorable safety profile of Opdivo, and durable responses in previously-treated patients
 Overall survival rate of 62% at 12 months observed at this interim analysis
 Hepatocellular carcinoma is the second most frequent cause of cancer-related death worldwide and remains an area of significant unmet medical need
 Patients with hepatocellular carcinoma who have relapsed or have disease progression, following standard of care, have a median survival with best supportive care of ~7 to 8 months

(PRINCETONN, JM, a2y92,015) - Bristol-MyerSsquibCbompany (NYSEB: MY) today announced resultfsromainnterimanalysiosCf A209-040Pa,hasIe/IdIose-rangintgriaelvaluatingthseafetyand

anti-tumoarctivitoyf Opdivo (nivolumabi)npreviously-treatedpa tientws ithepatocellulacrarcinoma
(HCCo)ardvancedlivecrancerI.nitiaflindingdsemonstratedthatthestimatedsurvivarlatien
evaluablpeatient(sn=47w) a6s2%a1t2monthRse. sultaslsoshowthseafetyprofiloef Opdivois generallcyonsistenwt iththaptreviously-reportefdor OpdivoiothetrumotrypesT. hesdeatwa ilble featuredtodayM, a2y9d,urinth5e1sAt nnuaMl eetinogtfhAe mericanSocietoyCf linicaOl ncology (ASCOp)resbsriefinga1t:020-:00p.mC. DTa npdresentedonSaturdayM, ay30from8:27a.m-.
8:39a.mC. DT(LatBe reakingAbstrac#t101).
"Hepatocellulacrarcinomiaasnaggressivaendfataclancerc,omprisin9g0percenotaflliver
canceirnadultws orldwidwe ithlimitedtherapeutiocp tionfsopratientws ithadvancesdtagdeiseasen;o treatmenatdvancehsavbeeenmadfeopratientws hofaitloresponodprrogresosnthceurrenstandard ocfare,s"aidAnthonyBE. l-KhoueiryM, Dl,eadstudyauthoarndassociatperofessoorcflinical medicinaenpdhaspIerogramdirectoartthUe niversitoySfouthernCaliforniNa orriCs omprehensive CanceCr enter".Thespereliminarydatarencouragingansdupportthoengoingevaluationof nivolumabinthipsatienptopulationa,tsheyshowpromisingpreliminarysurvivadlataa,ndurable
partiaolcrompletresponsienonoeuotffive nivolumab-treatepdatientsw, ithmanyothers experiencinsgtabldeisease."
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makinHg BV/HCVthme osctommorniskfactofrolriv ecrancewr orldwideP.atientws itahdvanced
HCCreceivingthceurrensttandardocfarheavmae edianoveralslurvivaollfestshany1earF.or
patientws hohavreelapseodhravdeiseasperogressionm, ediansurvivawl ithbesstupportivcearies approximately7to8months.
"Bristol-MyerSsquibb'esxperiencienhe patitiasndImmuno-Oncologmy akuepsoisedas
leadertsoadvance Opdivointoadditionasltudieoshfepatocellulacrarcinoma,s"aidMichaeGl iordano,
seniovricperesidentH, eadoDf evelopmentO, ncologyB, ristol-MyerSsquibb". demonstratedimprovementisnsurvivainlnaumbeordfifferenttumotrypesW. aerexcitedthatthis

Opdivohas

triahlasshownthpeotentiatlhatthims ayextend taodvancedlivecrancearndhopteoconfirmthese findingisnfuturterials."

About the CA209-040

CA209-04i0PashasIe/IdIose-rangingtriatlhaetvaluatedthseafetyanadnti-tumoarctivityof

Opdivoinpatientws itHh CCt,hme ajorityowf hom hadreceivedpriotrreatmentT. hteriailnclude4d7

HCCpatientws howerenrolledintonoetfhretereatmenatrmdsependingonwhetheornrotthey
werienfectedwithHCVoHr BVP.atientesnrolleidnthteriarleceived Opdivodosersangingfrom0.1-
1m0 g/kgintravenousleyver2yweekfsourpty2o
earsT. hperimaryobjectivwe assafetyt,olerability,
dosleimitingtoxicitiesa,ndmaximumtoleratedoseA. nti-tumoarctivitwy asasecondaryobjective
(usingRECIST1.1criteria)a,ndoveralslurvivawl aasnexploratoryobjective.
Aostfhiisnterimanalysis6,2%opfatientisn thsetudywersetilallivaefte1r2monthsE. ight
(19%p)atient(so4f2evaluablpeatientsa)chievecdaompletoeprartiarlesponsem, eaningthatthseize
otfheitrumorms easuredabtaselindeecreasedby30-100%with OpdivotreatmenIpnt.atientws ith responsed,uratioorfesponsreangedfro mortehan1.1-42.5monthsS.eventeenpatientrsemained
osntudytreatmenatn3d0discontinuedtreatmendtue toprogressivdeiseas(en =26)c,ompletreesponse
(n=2)o,ardversev ent(sn=2).
CA209-040itshfeirsttriatlocharacteriztehseafetyprofiloef Opdivomonotherapyinpatients
withHCCi,ncludintghoswe ithHCVanHd BVinfections
I.nthterials,afetyandtolerabilitywerwe ell-
characterizedw, i thferequencyandintensityotfreatment-relatedadversevent(sAEsb)eing
consistenatcross OpdivodosleevelsT. hme ajorityosfideffect
ws erme iltdomoderatienaturwe ith
abnormalliveernzyme(s19%ASTand15%ALT)r,ash(17%a)ndelevatioonafmylas(e15%a)nd lipas(e17%b)eingthme osctommont;haebnormalliveernzymeasndelevatedamylasaendlipaswe ere noatccompaniedbyanysignificanctlinicaslymptomsG. rad3e-4treatment-relatedAEws ere infrequen(t19%)T. herwe erneotreatment-relatedeathrseported.

About Opdivo

Bristol-MyerSsquibhbabasroadg,lobadlevelopmenptrogramtostudy Opdivoinmultiple
tumotrypecsonsistingomf ortehan50trial-asms onotherapoyirncombinatiown
ithothetrherapie-s
iwn
hichmortehan8,00patienthsavbeeenenrolledworldwide.

Opdivo becamtehfeirsPtD-1immunceheckpoinitnhibitotroreceivreegulatoryapproval

anywherienthwe orldonJuly42,014whenOnoPharmaceuticaCl oa.nnouncedthairtteceived
manufacturinganmd
arketingapprovailnJapanfotrhtereatmenotpfatientws ithunresectable
melanomaI.nthUe .S.t,hUe .SF.oodanDd rugAdministratio(nFDAg)ranteidtfsirsatpprovaflor Opdivofotrhtereatmenotpfatientws ithunresectable omr etastatimc elanomandiseasperogression following Yervo(yipilimumaba)ndiB,f RAFV600mutation positiveBa, RAFinhibitorO. nMarc4h,
2015, OpdivoreceiveditssecondFDAapprovaflotrhtereatmenotpfatientws ithmetastatiscquamous non-smalclellluncgance(rNSCLCw) itphrogressiononoarfteprlatinum-basedchemotherapy.

 Severpeneumonitiosirnterstitiallundgisease, includingfataclaseso,ccurredwithOPDIVO treatmentA. crostshcelinicatlriaelxperiencien 691patientws itsholidtumorsf,atailmmune- mediatedpneumonitiosccurredi0n.7%(5/691o)pfatientrseceivingOPDIVOn;ocases occurredinTriao1lTr ria3lI.nTria1lp,neumo nitisi,ncludinginterstitiallungdiseaseo,ccurred i3.4%(9/268o)pfatientrseceivinOg PDIVOanndonoetfh1e02patientrseceiving
chemotherapyI.mmune-mediatedpneumonitiosccurredin2.2%(6/268o)pfatientrseceiving OPDIVOo;nwe ithGrad3aendfivwe ithGrad2eI.nTria3li,mmune-mediatepdneumonitis occurredin6%(7/117o)pfatientrseceivingOPDIVOi,ncludingf,ivGe rad3aendtwoGrad2e caseMs.onitopratientfsosrignasndsymptoms opfneumonitisA. dministecrorticosteroidfsor Grado2egrreateprneumonitisP.ermanently discontinuOe PDIVOfoGr rado3ea4rnd withholdOPDIVOuntirlesolutionfoGr rad2e.

 InTria1ld,iarrheoacrolitiosccurreidn21%(57/268o)pfatientrseceivingOPDIVOand18% (18/102o)pfatientrseceivingchemotherapyI.m mune-mediatedcolitiosccurredi2n.2%(6/268)
opfatientrseceivinOPDIVOf;ivwe itGrad3aenod
nwe ithGrad2eI.nTria3ld,iarrhea
occurredi2n
1%(24/117o)pfatientrseceivinOg PDIVOG. rad3iemmune-mediatedcolitis
occurredin0.9%(1/117o)pfatientsM. onitopratientfsoirmmune-mediatedcolitisA. dminister
corticosteroidfsoGr rad2(eomf ortehand5aydsuration)3o,,c4rolitisW.
ithholdOPDIVOfor
Grado2e3rP.ermanentlydiscontinuOe PDIVO foGr rad4ceolitiosrrecurrenctolitiuspon restartingOPDIVO.

 InTria1lt,herwe aasinncreasedincidencoef livetresatbnormalities itnhOe PDIVO-treated groupacsomparedtothcehemotherapy-treategdroupw, ithincreaseisnAST(28%v1s2%), alkalinpehosphatas(e22%v1s3%)A, LT(16%v5s%)a,ntdotablilirubin(9%v0s)I.mmune- mediatedhepatitiosccurredin1.1%(3/268o)f patientrseceivingOPDIVOt;wwo itGh rad3e
anodnwe ithGrad2eI.nTria3lt,hiencidenceosifncreaseldivetresvtaluews erAe ST(16%), alkalinpehosphatas(e14%)A, LT(12%)a,ndtotablilirubin(2.7%)M. onitopratientfsor
abnormallivetrestpsriotroanpderiodicalldyuringtreatmentA. dministecrorticosteroidfsor
Grado2egrreatetrransaminaselevationsW.
ithholdOPDIVOfoGr rad2aenpdermanently
discontinuOe PDIVOfoGr rad3oe4irmmune-mediatehdepatitis.

 InTria1lt,herwe aasinncreasedincidencoeeflevatedcreatininietnhOe PDIVO-treategdroup acsomparedtthcehemotherapy-treategdrou(p13%v9s%)G. rado2e3irmmune-mediated nephritiosrrenadlysfunctiooccurreidn0.7%(2/268o)pfatientsI.nTria3lt,hiencidencoef elevatedcreatininwe a2s2%I.mmune-mediatedrenadlysfunction(Grad2eo)ccurredin0.9% (1/117o)pfatientsM. onitopratientfsoerlevat edserumcreatininperiotraonpderiodically duringtreatmentF.oGr rad2oe3srerumcreatininelevationw, ithholdOPDIVOandadminister corticosteroidsiw;f orseninognroimprovemenotccursp,ermanentldyiscontinuOe PDIVO. AdministecrorticosteroidfsoGr rad4seerumcreatininelevationanpdermanentldyiscontinue OPDIVO.

 InTria1lG, rad1oe2hrypothyroidismoccurredi8%(21/268o)pfatientrseceivinOg PDIVO
anndonoetfh1e02patientrseceivingchemotherapyG. rad1oe2hryperthyroidismoccurredin
3%(8/268o)pfatientrseceivingOPDIVOand1%(1/102o)pfatientrseceivingchemotherapy. InTria3lh,ypothyroidismoccurredi4. 3%(5/117o)pfatientrseceivinOg PDIVO. Hyperthyroidismoccurredin1.7%(2/117o)pfatientsi,ncludingonGe rad2ceaseM. onitor
thyroifdunctiopnriotroanpderiodicallydurintreatmentA. dministehrormonreplacement therapyfohrypothyroidismI.nitiatme edicaml a nagemenftocrontroolhfyperthyroidism.

 InTria1alnd3(n=385)t,hfeollowingclinical lysignificanitmmune-mediateaddversreeactions occurredin
anad
bducennservpearesisd,emyeliniationa,utoimmunneeuropathym, otodrysfunctiona,nd
vasculitisA. croscslinicatlrialosOf PDIVOadministeredadtose3ms g/kgan1d0mg/kg, additionacllinicallysignificanti,mmune-med iatedadversreeactionws eriedentified: hypophysitisd,iabetikcetoacidosish,ypopituitarismG, uillain-Barrséyndromea,ndmyasthenic syndromBea. seodnthseeveritoyafdversree actionw, ithholdOPDIVOa,dministehrigh-dose corticosteroidsa,ndia,fppropriatei,nitiatheormoner-eplacementtherapy.

 Basedonitms echanismoafctionO, PDIVOcancausfeetahlarmwhenadministeredtoa pregnanwt omanA. dvisperegnanwt omeontfhpeotentiarlisktfoaetusA. dvisfeemaleosf reproductivpeotentiatlouseffectivceontrace ptiodnuringtreatmenwt itOh PDIVOandfoart leas5mt onthasftetrhleasdtosoeOf PDIVO.

 IintsoktnownwhetheOr PDIVOipsresenitnhumanmilkB. ecausme anydrugsi,ncluding
antibodiesa,rexcretedinhumanmilkandbecaus
oetfhpeotentiaflosreriouasdversreeactions
inursinginfantfsromOPDIVOa,
dviswe omentodiscontinuberea stfeedindguringtreatment.

 InTria1ls,eriouasdversreeactionosccurredi4n1%opfatientrseceivinOg PDIVOG. rada3end
4adversreeactionosccurredin42%opfatientrseceivingOPDIVOT. hme osftrequenGt rad3e an4dadversderugreactionrseportedin2% t
 InTria3ls,eriouasdversreeactionosccurredi5n9%opfatientrseceivinOg PDIVOT. hme ost frequensteriouasdversderurgeactionrseportedin ≥2%opfatientws erdeyspneap,neumonia, chroniocbstructivpeulmonarydiseasexacerbationp,neumonitish,ypercalcemiap,leural effusionh,emoptysisa,npdain.

 Thme osctommonadversreaction(s
≥20%r)eportewd ithOPDIVOinTria1wl erreash(21%)
anidnTriaw3l erfeatigu(e50%)d,yspne(a38%m),usculoskeletaplai(36%)d,ecreased appetit(e35%)c,ough(32%)n,ause(a29%)a,ndconstipation(24%).
Pleasseee U.SF.ulPlrescribingInformation foOr PDIVO.

Immuno-Oncology at Bristol-Myers Squibb

Surgeryr,adiationc,ytotoxioctrargetedtherapiehsavreepresentedthme ainstaoycfancer
treatmenotvetrhleassteveradle cadesb,ultong-termsurvivaalnd remainedelusivfeomr anypatientws itahdvancedisease.
paositivqeualitoylfifheave
Toaddrestshiusnmemt edicanleedB, ristol-My erSsquibiblseadingresearchinaninnovative fieldocfancerresearchandtreatmenktnownaIsmmuno-Oncologyw, hichinvolveasgentws hose primarymechanismitsoworkdirectlywiththbeody'ismmunseystemtofighctancerT. hceompanyis explorinvgaarietoycfompoundasndimmunotherapeutiacpproachefsopratientws itdifferenttypeosf canceri,ncludinrgesearchingthpeotentiaolcfombininIgmmuno-Oncologyagenttshattargedtifferent pathwayistnhtereatmenotcfancer.
Bristol-MyerSsquibbicsommittedtoadvancintghseciencoeIfmmuno-Oncologyw, iththgeoal
ocfhangingsurvivaelxpectationasntdh
we apyatientlsivwe ithcancer.

About Bristol-Myers Squibb

Bristol-MyerSsquibbigaslobabliopharmaceuticaclompanywhosme issionitsdoiscover, develoapndeliveirnnovativme edicinetshahtelpatientpsrevaiolvesrerioudsiseasesF. omr ore informatioanbouBt ristol-MyerSsquibbv,is iwt ww.bms.comofrollowuosTn witteart
http://twitter.com/bmsnews.

This press release contains "forward-looking statements" as that term is defined in the Private

Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and

involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward- looking statement can be guaranteed. Among other risks, there can be no guarantee Opdivo will receive regulatory approval for an additional indication in hepatocellular carcinoma or advanced liver cancer.

Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December

31, 2014 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

###

MediaC: arriFeernandez2,15-859-2605, carrie.fernandez@bms.com kSahah9,08-447-6134, priyanka.shah1@bms.com

BilSlzablewski6,09-252-5864w, illiam.szablewski@bms.com

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