ONO PHARMACEUTICAL : Bristol-Myers Squibb's Opdivo (nivolumab) Receives Breakthrough Therapy Designation from U.S. Food and Drug Administration for Advanced Renal Cell Carcinoma (157KB)

September 17, 2015

(PRINCETON, NJ, September 16, 2015) - Bristol-Myers Squibb Company (NYSE: BMY) announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to Opdivo for the potential indication of advanced or metastatic renal cell carcinoma (RCC). The Breakthrough Therapy designation is an FDA program intended to expedite the development and review of medicines with early signals of potential clinical benefit in serious diseases to help ensure patients have access to new therapies as soon as possible.
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. In EU, Opdivo was approved for the treatment of advanced (unresectable or metastatic) melanoma in adults regardless of BRAF status in June 2015. European Commission approved Nivolumab BMS for the treatment of locally advanced or metastatic squamous NSCLC after prior chemotherapy in July 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, Urothelial 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, Hodgkin Lymphoma, Urothelial Cancer and Glioblastoma.
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

Bristol-Myers Squibb's Opdivo (nivolumab) Receives Breakthrough Therapy Designation from

U.S. Food and Drug Administration for Advanced Renal Cell Carcinoma

(PRINCETONN, JS,eptembe1r62,015) - Bristol-MyerSsquibCbompany (NYSEB: MY)

todayannouncetdhatthUe .SF.oodandDrugAdministration(FDAh)agsrantedBreakthroughTherapy Designationto Opdivo fotrhpeotentiailndicationoafdvancedomr etastatircenaclelclarcinom(aRCC). ThBe reakthroughTherapdyesignationiasnFDAprogramintendedtoexpedittehdeevelopmenatnd reviewomf edicinews ithearlysignalospfotentiacllinicablenefitnserioudsiseasetshoelpensure patienthsavaeccestsonewtherapieasssooanpsossible.
ThidsesignationibsasedonresultosCf heckMa t-e025Pa,has3setudtyhaetvaluatedthe survivaolpfatientws itphreviouslytreatedadvanc eodmr etastaticlear-celRl CCversuesverolimusa, currensttandardocfarfeopratientws itphreviouslytreatedkidneycancerT. hteriawl asstoppedearlyin July2015becausaenassessmenctonductedbythiendependenDt atMa onitoringCommitte(eDMC) concludedthatthsetudymeittpsrimaryendpoinotofveralslurvivald,emonstratingsuperioorverall survivailnpatientrseceiving OpdivocomparedtothceontroalrmB. ristol-MyerSsquibwb ilble presentingfurthedratfaromthisstudyatthe upcoming2015EuropeanCanceCr ongres(sECC)a,nd lookfsorwardtsoubmittingthesdeata toregulatoryauthoritietshiysear.
MichaeGl iordanos,eniovricperesidenth,eadoDf evelopmentO, ncologcyommented",Results
fromCheckMat-e02m5 arkthtehirtdumoirnwhich Opdivo hashown anoveralslurvivablenefiitna
Phast3erialT.BhereakthrougTh
herapyDesignatioinadvancedrenaclelclarcinomiacasleasrignal
otfhneeefdoardditionatlreatme natpproachefsoRr CCanrdeflects parotofubrroadcommitmentto
Immuno-Oncologyresearchthamt ayaddresms anytypeosafdvancedcancers." AccordingtothFeDAt,hceriterifaoBr reakt hroughTherapyDesignationrequirepsreliminary
clinicaelvidenctehadtemonstratetshme edicinme ayhavseubstantiailmprovemenotnalteasotne clinicallsyignificanetndpoinotvearvailablteher apyT. h itshfeourthBreakthroughTherapy Designationgrantedfor Opdivo bythFeDAw, ithpreviouisndicati onisncludingpatientws ithHodgkin
lymphomaftefrailuroeafutologousstemceltlransplanatnbdrentuximabp,reviouslytreatedadvanced melanom a,ndpreviouslytreatendon-squamounson-smalclelungcancer.

About Renal Cell Carcinoma

Renaclelclarcinom(aRCCit)shme osctommontypoekfidneycanceirnadultsa,ccountingfor morteha1n00,00d0eathws orldwid eacyhearC. lear-celRl CCitshe mosptrevalenttypoeRf CCand
constitute8sp0ercentto9p0ercenotaflclasesR. CCiaspproximatelytwicaecsommoninmenaiists
iwn
omenw, itthhheighesrtateostfhdeiseasfeoundinNortAh mericanEd
uropeG. loballyt,hfeive-
yeasrurvivarlatfeotrhosdeiagnosedwithmetastatico,ardvancedkidneycanceri1,s2.p1ercent.

About Opdivo

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

Opdivoipasrogrammedeath-(1PD-1i)mmunceheckpoinitnhibitotrhahtarseceivedapproval

fromthUe .SF.oodanDd rugAdministration(FDAa)mas onotherapiyntwocanceirndications. Opdivo
becamtehfeirsPtD-1immunceheckpoinitnhibitotroreceivreegulatoryapprovaalnywherienthe
worlodnJul42,014wheOn noPharmaceutical Coa.nnouncedthairtteceivedmanufacturingand marketingapprovailnJapafnotrhtereatmenotpfati entws ituhnresectablme elanomaI.nthUe .St.,he FDAgranteditfsirsatpprovaflor Opdivofotrhtereatmenotpfatientws ithunresectabloemr etastatic melanomandiseasperogressionfollowing Yervo(yipilimumaba)ndiB,f RAFV600mutationpositive, Ba RAFinhibitorT. hiisndicationiaspprovedundearcceleratedapprovablasedontumorresponsreate andurabilityorfesponseC. ontinuedapprovaflotrh iisndicationmaybceontingenutpovnerification andescriptiooncflinicablenefitnthceonfirmatorytrialsO. nMarc4h2,015, Opdivoreceivedits secondFDAapprovaflotrhtereatmenotpfatientws i thmetastatiscquamounson-smalclelllungcancer
(NSCLCw) ithprogressionoonarfteprlatinum-basedchemotherapyO. nJuly20t,hEe uropean
CommissionapprovedNivolumabBMSfotrhtereatmenotlfocallay non-smalclellluncancearfteprriocrhemotherapy.

dvanceodmr etastatiscquamous

 Severpeneumonitiosirnterstitiallu ndgiseasei,ncludingfataclaseso,ccurredwithOPDIVOtreatment.

Acrostshcelinicatlriaelxperiencien691patients withsolidtumorsf,atailmmune-mediatedpneumonitis occurredin0.7%(5/691o)pfatientrseceivingOPDIVOn;ocaseosccurredinTria1olTr ria3lI.nTria1l, pneumonitisi,ncludinginterstitiallungdiseaseo,ccu rredin3.4%(9/268o)pfatientrseceivingOPDIVOand

nonoetfh1e02patientrseceivingchemotherapyI.mmune-mediatedpneumonitiosccurredin2.2%(6/268o)f patientrseceivingOPDIVOo;nwe ithGrad3aendfivwe ithGrad2eI.nTria3li,mmune-mediated pneumonitiosccurredin6%(7/117o)pfatientrseceiv ingOPDIVOi,ncludingf,ivGe rad3aendtwoGrad2e casesM. onitopratientfsosrignasndsymptomospfneumonitisA. dministecrorticosteroidfsoGr rad2oer greateprneumonitisP. ermanentlydiscontinuOe PDIVOfoGr rad3oe4arndwithholdOPDIVOuntil

resolutionfoGr rad2e.

 InTria1ld,iarrheoacrolitiosccurredin21%(57/268o)pfatientrseceivingOPDIVOand18%(18/102o)f patientrseceivingchemotherapyI.mmune-mediatedcolitiosccurredin2.2%(6/268o)pfatientrseceiving OPDIVOf;ivwe ithGrad3aendonwe ithGrad2eI.Tn ria3ld,iarrheoaccurredin21%(24/117o)pfatients

receivingOPDIVOG. rad3iemmune-mediatedcolitiosccurred in0.9%(1/117o)pfatientsM. onitopratients foirmmune-mediatedcolitisA. dministecrorticosteroids foGr rad2(eomf ortehan5daydsuration)3,o,4r

colitisW. ithholdOPDIVOfoGr rad2oe3rP.ermanent lydiscontinuOe PDIVOfoGr rad4ceolitiosr recurrenctolitiusponrestartingOPDIVO.

 InTria1lt,herwe aasnincreasedincidencoelfiver tesatbnormalitieisnthOe PDIVO-treatedgroupas comparedtothcehemotherapy-treatedgroupw, ithincreaseisnAST(28%v1s2%)a,lkalinpehosphatase

(22%v1s3%)A, LT(16%v5s%)a,ndtotablilirubin(9 %v0s)I.mmune-mediatedhepatitiosccurredin1.1%

(3/268o)pfatientrseceivingOPDIVOt;wwo ithGrad3e

andonwe ithGrad2eI.nTria3lt,hiencidenceosf

increasedlivetresvtaluews erAe ST(16%)a,lkalinpehosphatas(e14%)A, LT(12%)a,ndtotablilirubin (2.7%)M. onitopratientfsoarbnormallivetrestpsriotroandperiodicallyduringtreatmentA. dminister corticosteroidfsoGr rad2oegrreatetrransaminaselevationsW. ithholdOPDIVOfoGr rada2end permanentlydiscontinuOe PDIVOfoGr rad3oe4irmmune-mediatedhepatitis.

 InTria1lt,herwe aasnincreasedincidencoeeflevatedcreatininienthOe PDIVO-treatedgrouapcsompared tothcehemotherapy-treatedgroup(13%v9s%)G. r ad2oe3irmmune-mediatednephritiosrenal dysfunctionoccurredin0.7%(2/268o)pfatientsI.nTria3lt,hiencidencoeflevatedcreatininwe a2s2%.

Immune-mediatedrenadlysfunction(Grad2eo)ccurredin0.9%(1/117o)pfatientsM. onitopratientfsor elevatedserumcreatininperiotroandperiodicallyduringtreatmentF.oGr rad2oe3srerumcreatinine

elevationw, ithholdOPDIVOandadministecrortic osteroidsiw;f orseningonroimprovemenotccurs, permanentlydiscontinuOe PDIVOA. dministecrorticosteroidfsoGr rad4seerumcreatininelevationand permanentlydiscontinuOe PDIVO.

 InTria1lG, rad1oeh2rypothyroidismoccurredin8%(21/268o)pfatientrseceivingOPDIVOandnonoef th1e02patientrseceivingchemotherapyG. rado1e2hryperthyroidismoccurredin3%(8/268o)pfatients receivingOPDIVOan1d%(1/102o)pfatientrseceivingchemotherapyI.nTria3lh,ypothyroidismoccurred in4.3%(5/117o)pfatientrseceivingOPDIVOH. yperthyroidismoccurredin1.7%(2/117o)pfatients, includingonGe rad2ceaseM. onitotrhyroidfunctionpriotroandperiodicallyduringtreatmentA. dminister hormonreplacementtherapyfohrypothyroidismI.nitiatme edicaml anagemenftocrontroolf hyperthyroidism.

 InTria1alnd3(n=385)t,hfeollowingclinicallysignificanitmmune-mediatedadversreeactionosccurredin

administehrigh-dosceorticosteroidsa,ndia,fppropriatei,nitiatheormoner-eplacementtherapy.

 Basedonitms echanismoafctionO, PDIVOcancausfeetahlarmwhenadministeredtpoaregnanwt oman.

Advisperegnanwt omenotfhpeotentiarlisktfoaetusA. dvisfeemaleosrfeproductivpeotentiatlouse effectivceontraceptionduringtreatmenwt ithOPDIVO andfoarlteas5mt onthasftetrhleasdtosoef OPDIVO.

 IintsoktnownwhetheOr PDIVOipsresenitnhumanmilkB. ecausme anydrugsi,ncludingantibodiesa,re excretedinhumanmilkandbecausoetfhpeotentiaflosreriouasdversreeactionisnursinginfantfsrom OPDIVOa,dviswe omentodiscontinubereastfeedingduringtreatment.

 InTria1ls,eriouasdversreactionosccurredin41%opfatientrseceivingOPDIVOG. rada3end4adverse reactionosccurredin42%opfatientrseceivingOPDIVOT. hme osftrequenGt rad3aend4adversderug reactionrseportedin2%to

 InTria3ls,eriouasdversreactionosccurredin59%opfatientrseceivingOPDIVOT. hme osftrequent seriouasdversderugreactionrseportedin ≥2%opfatientws erdeyspneap,neumoniac,hroniocbstructive pulmonarydiseasexacerbationp,neumonitish,ypercal cemiap,leuraelffusionh,emoptysisa,ndpain.

 Thme osctommonadversreeaction(s

≥20%r)eportedwithOPDIVOinTria1wl erreash(21%a)ndinTria3l

werfeatigu(e50%)d,yspne(a38%)m, usculoskeletaplain(36%)d,ecreasedappetit(e35%)c,ough(32%), nause(a29%)a,ndconstipation(24%).

PleasseeUe .S. FulPlrescribingInformation foOr PDIVO.

Immuno-Oncology at Bristol-Myers Squibb

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

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

I2n011t,hrougchaollaboratioangreemenwt ithOnoPharmaceuticaCl o.B, ristol-MyerSsquibb
expandedittserritoriarlighttsdoevelopancd
ommercialize Opdivogloballye,xcepitJnapanS,outh
KoreandTaiwanw, herOe nohadretainedalrlights tothceompoundatthteimeO. nJuly232,014,
Bristol-MyerSsquibbandOnofurth erxpandedth
ceompaniess'trategicollaborationagreementto
jointldyevelopancd
ommercializme ultipliemmunotherapie-asssinglaegentasndcombination
regimen-fsopratientws ithcanceirJnapanS,outhKoreandTaiwan.

About Bristol-Myers Squibb

Bristol-MyerSsquibbigaslobabliopharmaceuticaclompanywhosme issionitsdoiscover, develoapndeliveirnnovativme edicinetshahtelpatientpsrevaiolvesrerioudsiseasesF. omr ore informatioanbouBt ristol-MyerSsquibbv,isit www.bms.como,frollowuosnTwitteart
http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward-Looking Statement

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 that Opdivo will receive regulatory approval for the additional indication described in this release. 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.

###

Contacts:

Media:

CarriFeernandez6,09-419-5448c,ell2:15-859-2605, carrie.fernandez@bms.com

Investors:

RanyDa ajani6,09-252-5330c,ell2:15-666-1515 ranya.dajani@bms.com
BilSlzablewski6,09-252 -5894c,ell2:15-801-0906 william.szablewski@bms.com

distributed by