2023全球医药研发现状分析

WhitePaperPharmaR&DAnnualReview

2023by

IanLloyd,

SeniorDirector,

PharmaprojectsatCitelineReimaginingthefutureonechapteratatimeApril2023IntroductionWelcometoPharmaprojects’2023reviewoftrendsinpharmaceuticalR&D.Forover

30yearsnow,

I’vebeentakinganannuallookattheevolutionof

pharmaR&D,andinthisarticle,I’llexaminethestateof

playatthestartof

2023.We’llassessindustrytrendsby

examiningthepipelineby

company,therapeuticarea,disease,target,anddrugtype,usingdatafromprimarilyPharmaprojects,partof

theCitelinesuiteofproducts,whichhasbeentrackingglobaldrugdevelopmentsince1980.Thisreportwillbefollowedupby

ourannualsupplementreviewingtheNewActiveSubstancelaunchesfor

theyearjustpassed.Buthere,we’lltellthestoryof

pharmaR&Dasitistoday:anepictale,witharichcastof

charactersandaglobalscope,andnodoubtanumberofunexpectedplottwists.Hopefully,itwillbearealturner!thebestattention-grabbingfirstsentences,butanumbercomeupregularlyintop10s,sothereissomedegreeof

consensusof

whatconstitutesaclassicfirstsentenceconstruction.Amongthoserepeatedlycitedare:“Itisatruthuniversallyacknowledged,thatasinglemaninpossessionof

agoodfortune,mustbeinwantof

awife”—Jane

Austen,PrideandPrejudice(1813);“ItwasabrightcolddayinApril,andtheclockswerestrikingthirteen”—GeorgeOrwell,1984(1949);“Ifyoureallywanttohearaboutit,

thefirstthingyou’llprobablywanttoknowiswhereIwasborn,andwhatmylousychildhoodwaslike,andhowmyparentswere

occupiedandallbeforetheyhadme,andallthatDavidCopperfieldkindof

cr*p,butIdon’tfeellikegoingintoit,

ifyouwanttoknowthetruth”—JDSalinger,TheCatcherintheRye(1951),and“All

thishappened,moreorless”—KurtVonnegut,

Slaughterhouse-Five(1969).Butperhapsoneof

themostfamousopeninglinestoanovelinhistorywhichbestdescribestheexperienceofpharmaover

thepastfew

yearscanbeborrowedfromCharlesDickens’seminal1859opus,ATaleof

Two

Cities:“Itwasthebestof

times,itwastheworstof

times,itwastheageof

wisdom,itwastheageof

foolishness,itwastheepochof

belief,itwastheepochof

incredulity,itwastheseasonof

Light,itwastheseasonof

Darkness,itwasthespringofhope,itwasthewinterof

despair.”Regularreadersof

thisreport(whichhasbeenrunningsince1993,soispresentedhereinits31stedition)willknowthatinrecentyears,I’vethreadedadifferentthemethrougheachedition,tohighlightpoints,todrawanalogies,andtoaddalittlecharacterintowhatcouldotherwisebearatherlengthynarrativethroughapotentiallydrearyparadeof

statistics,charts,andtables.Themesselectedsofar

haveincludedastronomy,movies,thenaturalworld,music,foodanddrink,sciencefiction,and,lastyear,

travel.Thisyear,

Idecidedtomakeafew

nodstotheworldof

literatureandbookstohelpillustratemypoints.Storytellingisasoldashumanityitself,andfictionhasalwaysbeenusedasaproxy

tohelpustounderstandtherealworld.Thebestliteratureenlightens,thrills,amuses,andengagesthereader.

I’m

certainlynoShakespeare,butIhopethatmywordswillthrow

somelightonthecurrentstateof

thepharmaceuticalindustry,inthesameway

thatagreatnoveldoesonthehumancondition.Ofcourse,it’stheCOVID-19pandemicthatI’mthinkingof

here.Agloballycataclysmicevent,itthrewtheentireworldintoturmoil,andplacedthepharmaceuticalindustryfirmlyatthecenterof

theaction.Suddenly,drugR&Dwassupposedtoridetoaheroicrescue,butatthesametime,awholesetof

newbarrierswere

beingthrowninthewayof

its

deliveringthemuch-desiredhappyending.Clinicaltrialshadtobepaused,labworkersfoundthemselvesmaroonedathome,andthewholescriptfor

drugdevelopmenthadtoberewritten.So,whatwillbemyopeninglinestothisyear’smagnumopus?Amemorablesetof

bonmotstopiquetheinterestof

thereaderisimportant.Various

onlinepollspickdifferentbooksashavingcontinuedonnextpage...IntroductionContinuedBut,asanygoodauthorwilltellyou,withoutjeopardy,there’snotensionandthusnostory.Whathasfollowed,duringatimewhenmanyofusfeltlikewe

were

livingthroughadystopiandramaworthyof

MargaretAtwood,wasanits

charactersandits

nuances.Inmanyways,eachdrugundergoesajourneylikeanyliterarycharacter.

We

are

introducedtoeachnewmoleculeatthestartof

thestoryduringitspreclinicaldevelopment,wherewe

findoutaboutits

definingqualities,its

strengthsandweaknesses,andits

potentialrole

intheemergingstory.Aswegothroughtheclinicalstagesof

development,somedrugsmove

forward,theirnarrativeenhancedbypositiveoutcomes,whereassomestumbleandfallonHardTimes(CharlesDickens,1854),andothercharactersare

completelykilledoff.

Asthewill-they-won’t-theyplotlinereachesits

denouement,thedramatictensionclimaxesaswe

waittoseewhetherthepowers-that-bewillgiveusthatlonged-forhappyending,orsealthedrug’sfatetoamoredownbeatfinalact.IfAll’sWellThatEndsWell(WilliamShakespeare,1623),thepharmacompaniesresponsiblefor

ourmolecule’ssuccesswillsoonbeembarkingonasequel.almostHomericquestfor

asolutiontoanalmostunprecedentedcrisis.Withthestoicismworthyof

ThomasHardy’sGabrielOak(FarfromtheMaddingCrowd,

1874),theindustryhunkereddownandjustgotonwithit.Almostunbelievably,thegoldenfleeceof

avaccinewasfoundinanincrediblyshorttimespan—itsdiscoveryturnedouttobemoreanovellathantheexpectedWarandPeace-likeweightytomeby

Leo

Tolstoy

(1869)—likeweightytome—allowingtheworldtoreturnrapidlytosomekindof

normality,andthepharmaindustrytoemergeasaGandalf-ishwizardleadingthepeopletopeaceandprosperity.Atthetimeof

writing,inJanuary2023,itfeels,intheWestatleast,asthoughthisdarkepisodeinourliveshaslargelydrawntoaclose.However,

withChinaunexpectedlyandsuddenlyabandoningits

much-vauntedbutultimatelydisastrouszero-COVIDpolicy,thestoryhasclearlynotquitefinisheditsfinalact.ItisexpectedthatChinawillnow

undergothebiggestwaves

of

infectionwhichtheworldhasyetseen.Quiteapartfromthedevastationlikelytobewreakeddomestically,theconsequencesfor

theworldatlargeremaintobeseen.There’snothingthatthecoronaviruslikesmorethanahugecastof

supportingcharactersinwhichtofermentthepotentialcurveballof

anewvariant.Asserializednovelsoftenstate,To

becontinued…So,settledowninyourfavoritechair,

pouryourselfamugoraglassof

whateverisyourchosentipple,andlet’sopenthepagesonthestoryof

2023.Guidingyouthroughthecastof

charactersandtheinevitabletwisty-turnyplot,I’llbeyournarrator.

Ifyou’re

sittingcomfortably,I’llbegin.“Thebeginning

isalways

today”MaryShelley,ShortStoriesVol.

II(2014)Butitappearsthatthepharmaceuticalindustryisemergingfromthistumultuousepisodestrongerandemboldened,and,whilemaintaininganindependentcriticaleye,tomisquoteShakespeare’sJulius

Caesar(1599):“Friends,Romans,countrymen:We

are

here(largely)topraisepharma,nottoburyit.”Trends

inthepharmaceuticalindustrycanbeasopaquetotheonlookerasthatfamouslyunreadablenovel,James

Joyce’s

Ulysses(1922),somyaimhereistounravelallthecompetingandconflictingplotstrandsthreadingthroughthestoryof

pharmaceuticaldrugdevelopmentasitstandsatthestartof

2023.Thinkof

meastheliterarycriticaddingcompanionnotesandexplainerstothemaintextof

thetale.I’m

hopingthatmytextwillserveasfootnotesoranexplanatorycommentarywhichwillhelpyouuntanglethestoryof

R&Dtoday,ContentsChapterOne

–AnIntroduction:Total

PipelineSize0507102137434751Pharma’sstoryhasabiggerword

countthaneverChapterTwo

–SettingtheScene:The2023Pipelineby

PhaseMorewords,butdoesthatmeanlonger,

less-digestiblesentences?ChapterThree–DramatisPersonae:Top

CompaniesMaincharacterstakeasmallerrole

inourcastof

thousandsChapterFour

–TheMotivationsPropellingEvents:Top

TherapiesCancerstilltheindustry’smaincalltoarmsChapterFive

–DeusExMachina:MechanismsandTargetsImmuno-oncologyleadingsubtleshiftsinmostpopularproteinstohitChapterSix

–ModusOperandi:Types

of

PipelineDrugsTo

biotechnologyornottobiotechnology—thatisthequestionEpilogue:WhereNextfor

thePharmaSaga?Couldglobaleventssendtheindustryoff

topic?AbouttheAuthor4April2023CopChapterOne

–AnIntroduction:Total

PipelineSizePharma’sstoryhasabiggerword

countthaneverAsaforwardtothisyear’stome,let’ssetthescenewithanoverviewof

thescopeof

ourstory—somethingakintothemapsof

MiddleEarthoftenpresentedinthefrontispiecesof

thenovelsof

J.R.R.

Tolkien

—by

lookingatthetotalnumberof

drugscurrentlyintheR&D“pipeline.”Allof

theanalysesinthisreportwillbefocusingonthissetof

drugs,soit’sworthstartingoff

withadefinitionof

whatwe

exactlymeanby

theterm“pipeline.”Here,we

are

countingalldrugsindevelopmentby

pharmaceuticalcompanies,fromthoseatthepreclinicalstage,throughthevariousstagesofclinicaltestingandregulatoryapproval,anduptoandincludinglaunch.Launcheddrugsare

stillcounted,butonlyiftheyare

stillindevelopmentfor

additionalindicationsormarkets.Drugswhosedevelopmenthasbeenterminated,oriscomplete,are

notincluded.Alldatawere

collectedon3–4ofJanuary2023.Withthepastfew

volumesof

thedrugdevelopmentsagasofullof

incidentandintrigue,now

isperhapsthetimetotakestockandgetsomeperspectiveonwhereourworldisandits

directionof

travel.Figure1certainlyshowsthatthisepisodehasoncemoreincreasedits

word

count,astheoverallpipelinesizehasagainhitanewhigh,with21,292drugsindevelopment.Thisrepresentsa5.89%expansionof2022’snumber,

whichisadmittedlyalower

growthratethanthatseenlastyearof

8.22%.However,

itisupfrom2021’s4.76%,and,crucially,isnotlaggingfar

behindthe6.90%whichisthefive-yearaveragegrowthrate.So,perhapsitisamorestableandsustainableincreaseaspharmasettlesdownafterthedramasof

thepastthreeyears.FIGURE

1:

Total

R&Dpipelinesize,by

year,

2001–23Source:Pharmaprojects®,January202325,00020,00015,000U10,000DR5,0002001200200320042005200620072008200920102011YEA201R2013201420152016201720182019222025April2023CopChapterOne

–AnIntroduction:Total

PipelineSizePharma’sstoryhasabiggerword

countthaneverThismeansthatthereare

1,183moredrugsindevelopmentthantherewere

thistimelastyear,

comparedtothe1,527-drugriseseenlastyear,

andthe845-drugupliftreportedtheyearbefore.Intotal,5,082newdrugswere

addedtothePharmaprojectsdatabaseduring2022—considerablyfewer

thanthe6,343addedduring2021.Buttherewasdefinitelysomethingof

a“COVID-bounce”contributiontothatyear’sfigure,aslastyear’snumberwasstillinexcessof

the2020numberof

4,730.Asourcontinuousreviewsofcompanies’pipelinesgetevermoreuptodate,itcertainlyfeelslikeaddingaround5,000newdrugseachyearisatruerrepresentationof

thenumberof

newcandidatesadvancedintodevelopmentina12-monthperiod.far

outinfrontwith1,840candidates,butChinaiscomingupontherailswith1,457.

Ofcourse,we’llbeexaminingthepipelineasawholeby

allof

theabovemeasuresinmuchmoredetaillater.So,thisyear’sbookof

R&Disevenmoreof

adoor-stoppingmagnumopusthanever.

Asalways,we

caveattheexcitementatabigger-than-everpipelinewiththewarningthatthevastmajorityofthesedrugsare

stillprelaunch,soare

costswithrisksattachedratherthansuccessfulrevenue-generatorscuringpatients.2021onceagainwasarecord-beaterintermsof

thenumberof

NewActiveSubstances(NASs)successfullydebutingontothemarket,with97—far

outstrippingthepreviousrecordof

82seenin2020.Can2022comeclosetokeepingupwiththisphenomenaloutput?It’spossible:sofar,

we

are

reportingaround60NASsfor

2022,aboutthesamenumberwe

sawatthesamepointlastyear.

Aswe

furtherrefineourdatatowards

thespringpublicationof

ourannualNASSupplement,itwillcertainlybeinterestingtoseeif2022cangetwithintouchingdistanceof

2021.Afterall,abiggernovelisonlybetterifitsatisfiesthereadermore.But,asnotedearlier,

thesizeof

oursubjectmaterialisnotjustgovernedby

additions,butalsoby

whathasbeeneditedout.To

endupwithanetsurplusof

1,183drugs,havingadded5,082drugs,mustmeanthat3,899candidatesexited(pursuedby

abear?)theR&Dpipeline.During2022,282drugswere

confirmedasbeingdiscontinued(upfrom2021’s221),whileafurther3,804were

movedoutofthe“Active”

datasetasaresultof

beingmarkedas“Nodevelopmentreported”(down

from4,658thepreviousyear—notethatthefiguresdon’texactlysumasdrugscanmove

inandoutof

developmentinasingleyear).Overall,therewassomewhatlesschurnseenduring2022,althoughtherateof

fluxisstillprettyremarkable.“Ibelieve

there

isa

theorythatmenandwomen

emerge

finerandstronger

aftersuffering,

andthatto

advance

inthisorany

world

we

mustendure

ordeal

by

fire”Daphnedu

Maurier,

Rebecca(1938)Ofournewprotagonists,whereare

theirprimaryallegiances?Over40%of

newlyidentifieddrugcandidates—40.7%tobeprecise—are

targetedagainstatleastoneformof

cancer.

Thisisupfromthepreviousyear’sfigureof

38.8%,leavingneurologicals,with13.5%,adistantsecond.Interestingly,19.5%of

newcandidatesare

focusedononeormorerare

disease—asignificantriseonthe2021figureof

17.5%.

Intermsof

whichcompaniescontributedthemosttotheincreasedword

count,it’sfascinatingtonotethatfor

thefirsttimeitwasaChinesecompany,JiangsuHengruiPharmaceutical,leadingthepackhere.ThemoretraditionalcontributorsPfizerandRochefollowednext.Asregardstothelocationof

developmentof

2022’sbatchof

neophytedrugs,theUS

isstill6April2023CopChapterTwo

–SettingtheScene:The2023Pipelineby

PhaseMore

words,

butdoesthatmeanlonger,

less-digestiblesentences?PharmaceuticalR&D,likegreatliterature,hasabeginning,amiddle,andanend.Thisclassicthree-actstructureisoftencitedastheoverarchingtemplatefor

anyworkof

fiction,andhasfamouslycompany,soeachdrugiscountedonlyoncehere.What’simmediatelystrikingisthatour5.89%overallincreaseinpipelinesizethisyearisspreadfairlyevenlythroughoutthephasesof

development.Thisbeenadoptedby

themovieindustry.Ofcourse,most

hasn’talways

beenthecasehistorically:2022wasbooksare

reallymorecomplexthanthat.Similarly,arguably,drugdevelopmenthasthreemajor“acts”:preclinical,clinical,andregulatory,whichcanbebrokendownintosmallersections—thephasesofdevelopmentwe

usehereinPharmaprojects.moretypicalinthatlargerincreaseswere

seenattheearlierstagesof

R&D,decliningasthestoryunfolded.Indeed,lastyear,

thenumberof

drugsinpreclinicalgrew

by

asizeable11.0%;thisyear,thatrateisdowntoamoremanageable4.3%—actuallybelowtheoverallrateof

increasefor

once.Thismightreflecttheeffectof

ourreviewprocessbecomingmoreuptodateandthusagreaterproportionof

preclinicaldrugsbeingmovedtotheinactive“Nodevelopmentreported”status.Figure2breaksdownthe2023pipelineby

thedrugs’currentglobalstatuses.Globalstatusisthemostadvancedstageof

developmenteachdrughasreachedinanycountry,for

anydisease,andby

anyFIGURE

2:

Pipelineby

developmentphase,2023vs.2022Source:Pharmaprojects®,January2023-(N/A

=notapplicableandisappliedtocompaniondiagnosticsprelaunch)14,00012,00010,0008,000U6,000DR4,0002,000Preclin2022PhaseIPhaseIIPhaseIIIPre-regRegistered

Launched

SuspendedN/ASTAGE

OF

DEVELOPMENT20237April2023CopChapterTwo

–SettingtheScene:The2023Pipelineby

PhaseMore

words,

butdoesthatmeanlonger,

less-digestiblesentences?Incontrast,thenumberof

drugsinPhaseIclinicaltrialshasgoneupby

alargerpercentage,the2023ratecominginat10.7%,highereventhanthe10.1%seenlastyear.

Thenumberof

drugsatPhaseIIalsoshowedabiggerincreasethisyear,up7.2%

comparedto6.4%in2022,andPhaseIIIwasupby

9.8%,outpacingthe8.7%seentheyearbefore.So,onthefaceof

it,

theseare

veryhealthynumbers.Notethatthesedataare

asnapshotintime:thefactthatthereare

roughlythesamenumbersof

drugsinPhaseIIasthereare

inPhaseIinnoway

meansthatvirtuallyalldrugsundergoingPhaseIthenprogressserenelytoPhaseII.Infact,thereisconsiderableattritionbetweenthetwophases,butasPhaseIIdevelopmentgenerallytakesmuchlonger,

drugs“pileup”atthePhaseIIstage.It’sabitlikehow

atrafficjambuildsupwhenthemotorwaygoesdownfromthreetotwolanes.Figure3givesyouaslightlywiderhistoricalcontext,reallyhighlightinghow

thePhaseIandPhaseIInumbershavetakenoff

inrecentyears,andshowinghow

PhaseIIIhasreturnedtogrowthafterafew

moribundyears.Thesecondactof

ourpharmaR&Dnovelseemstobegettingbigger,althoughit’snodoubtaspackedwithincidentasever.FIGURE

3:

Clinicalphasetrends,2007–23Source:Pharmaprojects®,January20233,5003,0002,5002,000200720082009U15001,00050020102011DR201220132014201520162017201820192020202120222023PhaseIPhase

IIPhase

IIICLINICALSTAGE

OFDEVELOPMENT8April2023CopChapterTwo

–SettingtheScene:The2023Pipelineby

PhaseMore

words,

butdoesthatmeanlonger,

less-digestiblesentences?However,

onceagain,it’sgoodtoquestionwhethermorealways

meansbetter.

Afterall,moredrugsinclinicaltrialsmeansmorecosts,andthiscouldbeareflectionof

therenotbeingmorecandidates,butitcouldbethattheexistingcandidatesarespendinglongergettingthroughaphase,whichwouldclearlybeanegative.AnewreportfromtheDeloitteCentrefor

HealthSolutionstitled“Seizethedigitalmomentum:Measuringthereturnfrompharmaceuticalinnovation2022”certainlyhintstowards

thelatter,

calculatingthataveragecycletimes—thetimeittakesfor

anewdrugtoprogressfromstartingclinicaltrialstoapproval—increasedto7.09

yearsin2022from6.9yearsin2021.Atthesametime,theteamthereestimatedthattheaveragecostof

developingadrug,includingthecostof

failure,increasedfrom$1,986millionin2021to$2,284millionin2022.Taken

together,DeloittereportedafallinreturnoninvestmentinpharmaR&D.Now,

admittedly,thisreportisbasedonastudyat20leadingbiopharmacompanies,soisnotnecessarilygivinganindustry-widepicture.Butitdoesservetoillustratethefactthatit’salwayswisenottotakeeverythingatfacevalue.Just

asinagoodbook,thingsmaybenotquitewhattheyappeartobeinitially.Thingsare

seldomassimpleastheyseem,andit’salways

wisetotakeapeekbehindthewizard’scurtain.“Character

cannotbedeveloped

ineaseandquiet.Only

through

experienceof

trialandsuffering

canthesoulbestrengthened,

ambitioninspired,

andsuccessachieved”HelenKeller,

TheOpenDoor(1902)9April2023CopChapterThree

–DramatisPersonae:To

pCompaniesMaincharacterstake

asmallerrole

inourcastof

thousandsBecominganovelistissomethingwhichmanyofusdreamof.

Awholeindustryexistsaroundofferingadviceandtrainingcoursesonwhatmakesagoodreadandwhatare

its

essentialingredients.We’vealreadydiscussedtheimportanceof

anattention-grabbingopening,andof

havinganoverallof

agreatliterarynovelare

notjustvesselsfortheauthortotelltheirstory—theyare

thestory.Thecharactersinourtaleof

pharmaR&Dhavetobethepharmaceuticalcompaniesthemselves.Butwhoare

theleadswhocastthelongestshadowsover

ourstory?Table

1liststhetop25companiesby

pipelinesize,anditseemsthatwe

haveanewmaincharacter:Roche.TheSwissgiantusurpsitscompatriotNovartis,endingthelatter’sreignofsixyearsatthetop.ItwouldseemthatRoche’sascentislargelyorganic—itonlypostedonesmallacquisitionduringthepastcalendaryear,

thatofstructuretoyourtale.Oneattributethatyou’llfindeverynovel-writing“expert”includesintheirlististheneedfor

adiverseandwell-developedsetof

characters.Whocouldfailtobeentrancedby

thedeductivegeniusof

SherlockHolmes,themurderousartificeof

Tom

Ripley,ortheelaborateconstructthatisJay

Gatsby’slife?ThecharactersTABLE

1:Top

25pharmacompaniesby

sizeof

pipelineSource:Pharmaprojects®,January2023POSITION2023(2022)COMPANYNO.OFDRUGSINNO.OFORIGINATEDDRUGS2022TRENDPIPELINE2023(2022)1(2)Roche194(200)191(213)178(184)175(168)171(168)156(157)155(161)151(158)145(151)135(142)123(131)122(121)106(89)99(108)93(105)86(72)110112612(1)Novartis3(3)Takeda4(4)BristolMyersSquibbPfizer961058485725(5)6(8)Johnson&JohnsonAstraZenecaMerck&Co7(6)8(7)9(9)Sanofi826460459675635942585239413710(10)11(11)12(12)13(16)14(13)15(14)16(21)17(15)18(17)19(36)20(18)21(22)22(20)23(27)24

(23)25(24)EliLillyGSKAbbVieJiangsuHengruiPharmaceuticalsBoehringerIngelheimBayerGileadSciencesOtsukaHoldingsAmgen85(93)79(83)NovoNordiskEisai77(51)74

(80)Regeneron73(68)DaiichiSankyoCSPCPharmaceuticalShanghaiFosunPharmaceuticalBiogen70(75)68(62)53431864(68)63(66)10April2023CopChapterThree

–DramatisPersonae:To

pCompaniesMaincharacterstake

asmallerrole

inourcastof

thousandsGoodTherapeutics.ThegapbetweenthetwoBasel-basedgiantsisverysmallthough,andNovartisholdsontoitscrown

asthecompanyoriginatingthemostdrugs.Therestof

thetopfiveremainsunchanged,andindeedit’sstrikinghowmanycompaniesinthetablehaveverysimilarpipelinesizesnow

tothosepostedin2022,andhow

littlemovementthereisingeneral.Themostsignificantincreaseinpipelinesizewithinthetop25comesonceagainfromChina,andfromJiangsuHengrui.Afteraspectaculardebutinlastyear’slisting,itadvancesfurther,witha19.1%increaseinits

R&Dportfolio.ButChinesecompaniesdidnotmanageamajorlandgrabwithintheupperechelonsastheydidlastyear,

withCSPCPharmaceuticalbeingtheonlyChinesedebutantintheupperechelons.Theonlyothernewentryintothetableisthemorefamiliarfaceof

Novo

Nordisk.TheDanishconcernreturnstothebigtimethisyear,havingmadetwoacquisitionsduring2022,thoseofDicernaPharmaceuticalsandFormaTherapeutics.Fadingoutof

themainactionthisyearare

twoJapanesefirms:Astellas,whichfallsfrom19to26,andSumitomoPharma,droppingfrom25to28.Overall,Ican’trememberayearwhentherewassolittle

changewithinthetop

25andI

employed

thesymbolinthetable

somuch.Thisshould

probably

beviewed

asa

signof

stability

rather

thanstagnation.Notably,of

thetop10,onlyBristolMyersSquibbandPfizerhavelargerpipelinesizesthisyearthanlast.This,andtheoveralllackof

muchchange,canpartlybeaccountedfor

by

exceptionallylow

significantmergerandacquisitionactivityduring2022.AsidefromtheaforementionedRochetransaction,NovartisacquiredGyroscopeTherapeutics;BristolMyersSquibbtookoverTurning

PointTherapeutics;PfizerpurchasedBiohavenPharmaceuticals,ReViral,andArenaPharmaceuticals;AstraZenecaabsorbedTeneoTwo;SanofipurchasedAmunixPharmaceuticals;andEliLillyboughtAkouos.Inthegrandschemeof

things,theseacquiredcompanieswere

onlyminorcharactersdisappearingfromthestory,notmateriallyaffectingthesizeof

theirnewparents’pipelinestoanygreatdegree.Meanwhile,Takeda,Johnson&Johnson,andMerck&Codidn’treportanydealsof

relevance.Thelandscapefor

dealsthrough2022remainedlowonincident,withonly81mergersandacquisitionsreportedby

Pharmaprojectsduringtheyear,

afallfrom2021’s116,andcontinuingadownwardtrend.Manyindustryobserversseemtothinkthat2023mightbetheyearwhentheM&Aplotcomesbacktolife.QuotedinScrip,RichardWilson,seniorvicepresidentatAstellasGeneTherapies,commentedthat,“During2022,therewasacommonquestionof

‘havewe

reachedthebottomyet?’aswe

sawcompanyvaluationsdropdramatically,corporateambitionsshrinkand,sadly,valuedemployeeslaidoff

ascompaniesreactedtothechallengingmacroeconomicenvironment.M&Afeelspoisedtoheatupalittlemore.”Similarly,SarahHowell,CEOof

reformulationspecialistArecorTherapeutics,wasalsobullish:“Ibelievethatwe

willseeasurgeinM&Ain2023afteraquiet2022,”shesaid.“Pharmaare

sittingonsignificantcapitalreservesandthemodelof

accessingexternalinnovationisstillverymuchalive!”11April2023CopChapterThree

–DramatisPe