美股生物科技与制药业：谁会成为2020年代IBD市场的赢家

1、Global Biotechnology&PharmaWhoWillWinthe2020sinIBD?ASInflammatoyBoelDiseasePrimerAprl1,221Equity Reserch AmeicasResearchAnalstsMtinute,MD+1 212-325-6573 HYPERLINK mailto:martin.auster mati.atrcrit-i.cmMkCnnoly+1 212-325-7576 HYPERLINK mailto:mark.connolly mak.cllycrit-i.cmigouth+1 212-325-7569 HYPER

2、LINK mailto:tiago.fauth tiag.fatcrit-i.cmhosDel+1 212-325-3719 HYPERLINK mailto:thomasavery.deal tmaavry.alcrit-i.cmEuopeanPhaaem+44 207 888 0304 HYPERLINK mailto:creditsuisse.pharmateam critsi.amatamcrit-i.cmMttMiic+1-212-325-4381 HYPERLINK mailto:matt.miksic matt.miksiccrit-i.cmEvanSeigeman+1 21-3

3、25-4463 HYPERLINK mailto:evan.seigerman va.sigrmacrit-i.cmISLOSURE APPENDIX AT THE BACK OF THIS REPORT ONTAINS IMPORTANT DISLOSRES, ANALYST CERTIFICATIONS, LEGAL ENTITY DISLOSURE AND THE STATUS OF NON-S ANALYSTS. US Dislosure: editSuise does nd ees to do busines ih ompnies oveed in is eeah epos. s a

4、 eul, invesos hould be aware hat he Fim my hve a onflict of ineest hat ould afect he objetiviy of his epor. Invesos hould onider his epot s only a ingle or in ming heir invement deision.ableofContentsoElestge orl antintegrin5IntrctintoIBDOveiew - UC and CD6oEaliestage antLA mAbs ElrngKeyTeraeuticCla

5、ssesoOveiew of other progrms oEleElrngKeyTeraeuticClassesoOveiew of other progrms oElestge orl ohe BD tetment pdigm 9oClincal data summayoClincal data summay chats EltinfteIBDMarket ompact of orl agents JKs/SPs oBiologics antiompact of orl agents JKs/SPs oBiologics anti-integrin oSomething big is ge

6、tting bigger oPaer considertions oBiologics nextgen BoPaer considertions oBiologics nextgen IBDPyscianSreyoOral small molecules JK inhibtors Oveiew of biologics IBDPyscianSreyoOral small molecules JK inhibtors oSuey data oNovel orls YK2s a saer JK? Novel orls gut selectieoSuey data oNovel orls YK2s

7、a saer JK? Novel orls SP receptor modultors AenixCatalstlst,Parmaales EecutiveSummaryInIntisreprt,weferaeepiermernteinflammatryweldsease(IB)market,incling:An nroducton o IBD (Ucerave Cos nd Crohns sese) nd overvew of he IBD rement prdgm.A comprehensve dscusson of ey herpeuc clsses (pproved nd n clnc

8、al developmen).CS views on he evoluon of he IBD mare, ncludng mplcaons for our coverge.A proprery survey of 27 US. gsroeneroogss, coverng he rement ndscape nd emergng herpes.eyaeawysTheIBDmarketisisedfrcontinuedrwthasnexteratinaentsreachtemarket.The IBD maret pproched $20Bn 2020 WW ses per Evuehrm.

9、espe maret growth, response res o esng herpes reman subopma, nd pens ofen ose response over me; s a resu, pens commonly cycethrohmutechronictherapes.Hsorcal rectores of more maure mmunology mares (eg, psorss, RA, S) suggest mple room for contnued growth as mproved gens come o maret (ncludng novel or

10、s nd more convenent boogcs); we seek a pek WW IBD maret opporuny of $30B+.The propensy for pens o cyce hrough herpes enabesnewentrantstogarnersharend suppors severl herpeuc clsses; mong ne-erm enrns, we epect orl AK nhbors, orl S1P receptor modulors, nd IL-23 mAbs mayalachevebocksercasssaes.Eltinfmr

11、eefecieandralaentsisteexectedrerfmarketexansin;weexectJAKsandS1Psto larelycometeiniferentmarketsements.hscin feedbck contnues o suggest AK nhbors wl be used s er-ne gens for refrctory pens, due o clss sfey rss; bsed on FDA commenry nd our revew of daa, we beeve Rinvoq, f pproved t 45mg n UC, s unlke

12、ytochangethspardgm.enwhe, we epect S1P modulors o emerge s rctve erer-ne gens for pens on he moderaeend of he severy specrum; ourOL dscusons suggest hs s a prcury underpenetredsegmentn boh UC nd C, nd my be a eydrverofmretgroth.In hs seng, we see a hghy rctve $35B+peakopprtniyfor he S1P clss (f succ

13、essful n boh UC nd C), nd beeve a best-n- clss gent may capure maory shre whn he clss.EecutiveSummaryIncreasedisimlarcmetitinislming,tisunlikelytopeenttakefnelaents.Bosmrs f Humra (he rgest drg n IB) re epeced o ener he mret n ; we noe cve per mngement n IB, nd beevebosmir eroson of Humia may be rev

14、ely rpd (consient wh consensus epectons).We epect ht enry of Humia bosmirs (n ddon o esng Remcade bosmir) may furtercementantisasthefrstne boocoptn, but we do not epect bosmirs wl se he mares ppee for novel mechnsms nd mproved dminsron convenence.ens cycng hrough herpes, n ddon o n esng pool of boog

15、c-eperenced pens, wl contnue o support upe of novel gens; ccordng, we donotepectbosmarstomeanngfympedeuptaeofnovelagentswh compeve product profes.Lngeterm,IBDremainsanattractieinicatinfrrgevelment,itharchclnicalieline.Amd n ncreasngy compeve (nd maurng commercl ndscape), we contnue o view IBD s n rc

16、tve ndcaon for dug developmen; no herpy n development hs demonsred gme-changing or meanngfuy dfferened effcac, eving room for new enrns to compee.Among ere-sge mechnsms, phscins ndcae enhussm for addtnalsafe,effectveoralagentsht can repce mechnscay smir boogcs (nc. K2,oralntegrnnhbrs, ec); precsionm

17、edcneapproacesarebroadyntrgun, nd may heorecay drve greer effcacy n seect pent popuons.itinrceraenierse,weilttwonamestatmayenefitfrmtesemarkettrens:AeaPhmceuticlsARNA;Outpeform,$02P.We ggt ARA as a tp k n r vrage vrs. Lad asst, trasi, s a magfly e-rskd ttal st-ass S1P matr n BD (may ave srr ffay th

18、a fast stffst, ad o ttratn rrmt). 3 rats fr trasid n C are td n 12.We ve rrt sare rs ffr a gy attratve LT try t, ad o t fy arate te mmral rtnty fr trasid n BD (e ml $2.B S-astd ak sals n C/CD). Ata, e te sstatal LT taty fr trasid n tr ats.ase rfr to r P rase te fr mre tad ssso.PometheusiosciecesRXDX

19、;Outpeform,$0P.RDXs ad rgram mrss RA03, a vl at-LA mAb n ase 1 vmt fr BD, s a vl man agstc to tfy atts mst ky to rsd to tray (tse gtay rssed to gh LA rsson).RDX as to tate C sts n C ad CD n 31, wth ata rats cd n H222. We visty s mt, we ve tse rats d sgfatly -rsk te rgram ad te rsn m ara, th a ar sss

20、 gratg sstatal V se (p to 3-4x frm r rrt P). f ave rrt gc rsse rats are sn n te targtd at, e t te rgram to e vry l rvd y s.ase rfr to r rt tatn f vrage rrt fr mre tad ssso.InroductiontoIBDAage,CronicIndicationwithRemainingUnmetNeedIDisalgeidicatonwthahighbudenofdisese.Infmmaory bowel dsese (IB) gene

21、ry refers o wo condions charcterzed by chronic nfmmaon of he gsronesnl rct: Ulcerativeots(UC)nd rohnsDsese(D).There s n esmaed prevaent IBD popuon of 152Mpens n he US. one; one esmae suggess a US. prevaent UC popuon of 700-800K pens, nd a prevaent CD popuon of 900+ pens.UC nd CD re chronic, repsng/r

22、emng mmune-nfmmaory condions; here re genery no curave herpes (sde from proctocoectomy n UC).hethepeutcsnlsgong,butsubstnlunetneden.sese mangement hs mproved wh he emergence of mulpe effecve boogc gens; ddon, here s a rch herpeuc ppene n IB, nd severl new gens may rech he maret n he net 3-5 ers.Howe

23、ver, response res o esng herpes re subopmal nd responses re ofen ost over me, requrng pens o cycethrohtherapes; here remans subsnl unmet need for effcacious, sfe, nd convenent herpes, nd mny pens evenuy reure sugicl nerveon.CCmmn ymtms icl:Amial ai/latigUrgcy, ft tlsCric iaraBl/mcs in stlIn mre vre

24、ia, ymtms may icl:AmiaFvrFatigealtritinigt lsBwl trctin (CD)iae rn is ig, aticlaly in mrt/vre ia; rik f aitial LT cmlicatis icras with rtin ad vity f ia.IDSmptom urdenTheIDMarketConinuestorowitoricalWWSaleshemetforIDthepiesisbigndgettigbigge.The IBD maret s rge nd growing (pproching $20B n 2020 WW s

25、es), nd remansunderpeneraeddue o hsorcay few vabe herpes wh subopmal product profes.We beeve growth prospecs reman srong s emergng herpes (ncludng novel orl gens nd mprved boogcs) come o mre, epndng he rement ndscape nd eepng more pens n he rement oop; we see a hghyattractvemaret opporuny for he wnn

26、ers mong he net- generon of IBD herpeucs.B.B.B.BB.B.B.B.BB.BD0900UlcertiveColitisvs.rohsDiseaseeyDiffeencesUcerave cols nd Crohns dsese re he wo most common forms of IB; hough he ndcaons shre many smires, here re ey dfferences n presenon ht ow for dfferenl dgnoss.Whe boh UC nd CD can be que severe,

27、Crohns dsese s genery considered a more severe, ssue-desructve ndcaon, wh a subsnyhgher rsk of ned for sugicl nerveon.Ulcerativeots(UC)rohnsDisese(CD)Prvalece:Estimatd US valt latin f 700800Ktient.Pretation:Ulcative clitis is caactizd y iiatic ilammatin f te lrgeintetine ctm a/r cl, gally limitd to

28、te mcsa/smcsa te imst lays f te I tact).Disase tyically gis in te ctm ad in may cass sas ximally tgt te cl.isse is ytmats ad ial; tn ivlvs te vlmt f mcsal lcers a/r magig atcs wich ctite to l/mcs in te stl, t t istlas r ascsss as sn in Cs.Disasd aa is continuu, as sd to istict atcs f isasd wl saatd

29、y alty tisse Cs stati.Progoi:Disase is cic lilg) in 90% f atits; gsis vais y svity, t is gally avale r milr cass mal lie xctacy ad little isk f sgy.Elvatd rikfclncncer, icasig with xtt/atin f isas; isk is as igh as 18%+ atr 30 yas f isase.Up to 245%f atits ie sgical itvtin at sme it ig te cse f isas

30、.Prvalece:Estimatd US valt latin f 900Ktient.Pretation:In Cs isas, ilammatin may ccr nywereintheGItrctm mth to as; mst cmmly, Cs ivlvs te ilm ial tin f te small itsti) a/r te cl.Ilammatin is tn trnmral sas acss all lays f te wl wall, /me xtsive tan in UC.vacd isase ivlvs firoi/trictres ttially stcti

31、v, ad cees wich may vlp ito fitus tls r tacts m wl to tr ga/ski.Disase is tyically tchy, r gial, with istict aas f isasd tisse saatd y sctis f alty tisse skip aas.Progoi:Cs is a lilg laig ad mittig citi; tais/itvtis, iclig sgy, ae vy aly cativ.Data n cacr isk r Cs atits ae lss xtsiv/clar tan in UC,

32、t sme stis ave swn an icasd isk f clctal cacr ad igr liklid f mtality latd to GI tms.Histical ata sggst p to 3 f atitsie sgy ig isase cs.Source: redt Susse reserch; . crohnscotsfutonog; . tos et ., .; . rohns & ots foundton ID 7Whtdowekowboutpatogenesis?Riskfctosndpathophysioogyeicompletlyundestood.

33、Th1TNIFI-I-Th2I-4I-e atsoogy f BD s notwellundertood, t s tgt to vve an arrat tstal mme rsse tat may rst frm gtc rsstins ad s ky fed yTh1TNIFI-I-Th2I-4I-BD s mre mmn n e f Jsh r rtrn Eran st, ad a famy stry f BD sgfatly rass rsk; ste svry f may gtc rsk fatrs, te rtve vae f tse rsk fatrs n BD rmas r

34、(r e stmat, tfd rsk i an st 13.% ad 7.5% f CD ad C rtat, rstvy).Smkg s a ky rsk fatr fr Crs, t, trstg, may e assatd th a r rsk f C.AhistorcalviwofIDimunedysegultionisevolvig.Th17I-I-6TNHstra, CD as n rstd as a rmaty 1-matd sase (. ky tks F ad -1), e C as (mre trvrsal) assatd th a 2 mme rsse Th17I-I-

35、6TNTheTh1Th2paradigmhasevolvedamd al fgs (fr sta, te fare f ati-3 mAs n C, t.) ad a grg rgton f tr mx sgag atas (. te mrtae f 7 sgag).Dste avamts, BD rmas a trgeus ad ry rstod atn aratrzd y mx ataatve mme rss; n rat, BD may vve a rage r strm f stt GI tns tat are t t at.Mtchigpatetswththebestthepiesi

36、sveydiffcult.g to trgeos rstat, mtey rstd atsoog, ad a ak f gtimarkr rtrs f sas, t s rrty t sse to trme h atts l rsd st to h tras; Ls ate ts s an araofubtanialunmtned.DiagnosisadAssessngDiseaeSeveityIBD most commonly develops n e doescence/eary duhood (ges 15-30); dgnoss s confirmed via colonoscop,

37、upper endoscop, nd/or sgmoidocopy, ofen suppemened wh sool nd/or bood ess.At dgnoss, dsese severy s pcay ssesed usng n esbshed scoring ssem; he most common (nd preferred for clncal sudes) re he Myoncscorefor UC, nd he DIscorefor Crhns. Whe hee scors re mpont for clncal rs, phscins, n prcce, focus mo

38、re on pen-repored smpom burden, s wel s marers of dsese such s fecal caproectn, CRP, nd hemaocri, n deermnng trement decisons.UlcertiveColtisMyoScoeCohnsDiseseCDAIScoee ayo sce mas UC isae activity acrss 4 mis; ach minis scd m 0 mal) to 3 (v, r a ttal f 12 ttial its.A ttal sce m 06 iicats mild isas,

39、 wile 612 iicats mat/sve isas.2016 FDA at giace stalisd te 3main ayo sce as a d tial it, xclig te me sjctive ysicias glal assssmt PGA) mai; tis cage can make csstial cmaiss iiclt.lnilremiin, r 3min ayo sc, is id as 0, F0 r1 with 1 it case m asli, ad an scic ssce f 0 r 1.e s isae ctivity Ix I) sce ma

40、s isae activity acss 8 aamts. A ase sce is assigd to ach aamt, ad tn mltilid y a sciid wigtig act; tse wigtd scs ae tn smmd r a ttal sce t f 1,100 its.A sce f 150220 iicats mild to matly active C; 221450 iicats matly to svly active C; ad 4511,100 iicats svly active to lmiat C.lnilremii, r te I sc, i

41、s id as a ce m 0its, wile cinclrene is id as a 70100 it imvmt ig n sty.44mainaoClinicScrel Frcy (F)0+1+2+3rml tl frcy-2 ts r y mre tn rml -4 ts r y mre tn rml4 ts r y mre tn rmlcal g ()0+1+2+3o ge d n tl s tn f f te tme e d n tl mre tn f f te tme g re d e0rml rce r ctve ctscc+1M: md frty, rytmaFs+2M

42、rt: frty, mrd rytm, rs+3Svr: crts d ts gPycan al At0+1+2+3rmlMd cte ctvtyMrte cte ctvty Svre cte ctvtyCIScrePararWg(Mr)mr f d r ft ts n te t 7 ysml n (rd -), ttl f y crs fr ch f t 7 ysGrl l g frm 0 (t) to 4 (rt), (ttl f crs f t 7 y)Cmcts (e t fr c, cl c, ft, tc.)0Ue f t-rrs (xyt, t)0rce f ml m, crd

43、frm 0 () to 5 (ft)0te vtn f mtcrt frm rml (% m, % m)rct vtn frm trd tTalt f ,0 sUndestandingInductionadMaintenaceBrodl, there ae to goals of tretment in BD (both UC and CD): iductionand mitenceof remission.Inductionreers to the initial phase of tretmen, here the goal is to brng actie disease under c

44、ontrol (.e. induce remission) by reducing actie inlmmation and reieing symptom burden; induction therpy may reer to initial tretment foloing dignosis, or the tretment of a disse leAter remission (or response) is achieed on induction therpy, mitenceof remission becomes the goal of therpy (i.e., manta

45、nig disease control and preenting faeupsnduction tretment regimens may difer fom mantenance regimens. For exmple, a patient may be stated on corticosterods and an anti- inlmmatory biologic to induce remission; once a response is achieed, sterods ae commonly ithdrn, and biologic tretment continues.Wh

46、ile tral design aies, BD clincal studies generaly include an induction phase and a mantenance phase. Patients ae initialy rndomized to a tetment m or 612 ees the inuction phse, ter hich n eicacy nlsis is conucted. Floing the inuction phse, dug respondes ae rrndomized to actie drug or plcebo for the

47、mantenance perod, hich most commonly extends to 1 yer.aoaoMaineance aoaoMaineance eadoutRsrs RamzdInducton eadoutAtveAtveGray k 52Wk 6-OveriewofteurrentretmentLndscapeAn overvew of he IBD rement prdgm s ncluded beow; n he comng sdes, we epore chaenges of dsese mangemen, nd ey herpeuc clsses for he r

48、ement of moderae/sevre IB.Whe boh UC nd CD can be sevee, Crhns s genery unerood o be a more seous nd poeny ssue-desructve dsese (greer dmage can be done f dsese s eft unreed or poory manged); ccordng, rement of CD s pcay more ggressve (boogcs re commonly fronne gens n Crohns).-SAsUnderstanngthe Land

49、scapeUC ad CD are cric rlaig/rmittig ia; iae maagmt is a lfelong poce.atits cmmly cyclethoughmultiple thepiesvr te cre f te ia.ite a gwig tatic aal, LT outcoeseinuboptil, with may atits ririg rgical itrvti.Fr may id/oderteUCptients, tratmt gis with a 5-amialicylic acid (5-ASA) rg (cmmly malazi, lala

50、zi, laalazi, r alalazi).5-ASAs ae a clas f NSAIs fctive in icig ad maitaiig rmiin in UC.5-ASAs ae amiitrd rlly a/r tically (via ma r itry; ty ae ite sfe (t immmlatry) ad grlly wll-tlrt.ile itrically d in Crs, 5-ASAs ae w rtd to ave little mtry activity in CD ad ae rmiatly d in UC, tgh me 5- ASA e in

51、 Crs rmai.In aitin to 5-ASA, aly tratt my ivlve itary mificati, ati-iaral, tritial slmts, r atiitics (in cas wre ifctin is a ccr).SteoidImunomodulatorsCrtictris (ri, i, tc.) ae cmmly rcrid fr te tratmt f acte fla-s in IBD ndfor inductionofeiion; crtictris my e amiitd ally r tically (via itry, ma, r

52、am.Stris ae ftn rcrid in cmiatin with tr tris as at f an ictin rgim; atr rmiin is ic, tris ae ftn icti, ad te atit ctis n maitace try.Otr immlats icl. azatii, 6-mrcatri, mttrxat, cyclri, tc.) may e rcrid fr atits wo ae t wll-ctrlld n 5- ASAs + tri. Hwvr, e to riks f LT ytmic imme rin (d icraig avail

53、aility f tr trtic ti), te e f te immmlatrs in IBD is craig.dvancdTheapiesFr atits t aatly ctrlld n 5- ASAs a/r tr rtive tris (i. mrt/vre atits, ilgics ae te mt cmmn tratmt tin (mAs amiitrd I/SC); te thepiese eltivelyexpenive(me $70/ya).Arvd ilgics icle ati-TNF, ati- IL-12/23, ad ati-itgin agt; ach t

54、argts a cmt f te imm/iflmmatry r, ad cms with its wn rik/fit ad amiitratin cirti.In aitin to ilgic, newoltetent optionsfr mrt/vre atits ae giig to rach te makt, iclig JAK iiitrs ad S1P rctr mlatrs (icd latr in mre tail).SurgerySrgry is tyically cird fr atits with vry avacd ia, r wo ave xatd tr tratm

55、t ti.Hitrically, as may as 75%+f Crs atits ad 23-45%f UC atits ave rird rgry rig tir iae cr; wvr, tcms ae likly imrvig as te mr f availale tris as icra.1rctclctmy (mval f te lage itti) is te mt cmmn rgical itrvtin fr UC, ad is grlly crtiv; Crs rgris may ivlve a wir age f rgical rctis acrs te I tract

56、.DespiteAdvnces,ManyCallengesRemainThe vaby of mulpe effecve boogcs (ni-TN, n-negrn, nd n-IL-12/23) represens a sgnfcant dvancement n he mangement of IBD (prculry moderae/severe dsese); however, phscins ndcae ht he mangement of IBD remans chaengng nd ofen subopma.Chenges of dsese mangement nclude su

57、bopmal response res, mied duron of response, burdensome dminsron, nd subopmalcompnce o hepes; hee remns susnl unmt ned for novel hepes o epnd/mprve he rement ndcae fr IB.ChalngesofIDetmetResponseRtessse ats to IBD tais ae stimal; in cliical stis, laco ajstd missin ats in te 1020%ange are cmmn tgh ti

58、als ll avac/acty atits, ad alwl missin ats ae igResponseRtese ae ctly o availale imaks to accatly ict wich atits will sd to wich tais.Wn mission is acivd n tapy, sse is vy cmmnlylt vertime. In actic, tis tn lads to se scalatin may atits cive g moe tly tan labll) and vtally isctiati.Dution ResponseDe

59、lmet f atg atiis Ds) is tght to ctite to lss f sse in the case f ilgics, t te mn is icmpletlyDution ResponseAdminsttion ConveinceBilgics r mat/sve IBD ae amiistd itavsly IV) r sctasly C, ad ae cnieredAdminsttion ConveinceXljaz JKi, avd in 2018 r UC, is te ly availale al tay r mat/sve IBD t saty ccs

60、ave limitd s.e is sigiicat mt d r sae ad ctive al agts, as wll as ilgics with lst sig.Pysicians te timl cmlinceto tapies e to the mittig/lapsing ate f isase atits tn want to isctie tapy wn in missio) and n f ilgic tapies.Complnce hepiesHowv, isase cmmly lars wn atits isctie tapy tn witin a yar; anct