Clickhereorpressenterfortheaccessibilityoptimised

version2024ReviewTheLong&Winding

RoadClickhereorpressenterfortheaccessibility

optimisedversionForewordBiopharmaexpertsknewthat2024wasunlikely

tobetheyearthatpharmacameroaringbackin

ablazeofmega-mergers,highprofileIPOsandeye-wateringprivateinvestmentrounds.Andlookingbackontheyear,atleastwecan

saywedidn’tgetourhopesuptoomuch,despitewhatlookedlikeapromisingstart.Butwas2024adampsquib?Orwasitasmuchaswecouldreasonablyexpect

afterthepainof2023?Inthisround-upwe

lookatthedealmakinglandscapeofthepast12months,seekoutthehighsandlows,andconsiderwhatitmeansfortheyear

ahead.Let’sstartatthebottomandworkour

wayup:M&A.Abusyfirstquartersparkedhopesofareturntosomedynamicdealmaking,butthosehopesweresoondashed.Therestoftheyearslithereddownhillwithever-reducingdealvaluesandwasn’tevenrescuedbyaQ4

surgeaswe’dseenfortheprevioustwoyears.Thebestthatcanbesaidofyearendisthatdealvolume

increased.Inslightlybetternews,theIPOwindow

creakedopenalittlefurther.Totalflotationshit38–upfrom2023

and2022,thoughwellbelowtheCovid-inspiredpeakthatnearlyblewthewindowoffitshinges.ThereisnoshortageofprivatebiotechslookingtolaunchIPOsin2025,buttheyneedthefragilemarketstostabilizeandtheglobaleconomytosettlebeforetheytakethe

plunge.Ontothebetternews:venturecapital

fundraisingforbiopharmacompanieshadastrongyearend,boostingtheyear’s

totaltoover$28bnandbeating2023and2022.Therewereevensomemega-roundsfortheindustrytogetexcitedabout,includinga$400mseriesAroundforKailera,acompanyfocusedon–youguessedit–obesity.Backwithabump,thenthough,aswelookatafarfromvintageyearforbiotechintermsofstock

performance.Finally,welookatthedynamicsofsomeofthedrugsthathitthemarketin2024.Recentthemesremainapparentwithbiglaunchesaroundmetabolicdiseaseandneurologicalconditionsinthetop12list.What’smostinteresting,though,isthefactthathalfofthosetoplaunchesdo

notsitwithBigPharmabutinsteadwithsmallorfirst-time-to-market

firms.Ispharma’sglasshalffullorhalf

empty?Graba(full)cupofcoffee

andlet’sfindout…ForewordFormoretimely,data-driveninsightsinto

thepharmamarket,checkoutScripandIn

Vivo.Clickhereorpressenterfortheaccessibility

optimisedversionM&AValuesContinued

ToDeclineDuringQ42024Evaluatedatashowthatthebiopharmaindustrymade

$9.5bnofacquisitionsduringthefourthquarter,athirdconsecutivequarterofdecline,althoughdealvolumeroseto33fromQ3’s

29.Although2024gotofftoapromisingstartwithabusyfirstquarter,thefourthquartermarkedthethirdconsecutivequarterofdecliningbiopharmamerger-and-acquisitionvaluation.Evaluatereportedthattherewere33M&AdealsduringQ4,upfrom29inthethird

quarter,butwithatotalvaluationofslightlymorethan$9.5bn,downsubstantiallyfromnearly$52.3bninQ4

2023.Industrywatcherswerereadywiththeir

explanations

ofwhyM&Aactivityhadcrateredthroughout2024when

positiveconditionsappearedinplaceforsuchactivity

–

while

potential

buyers

had

bothcashandneedtoaddpipelineassetstooffsetcoming

revenuelossesduetopatentexpirations,macroeconomicuncertainty,especiallyinthefinancialmarkets,andtheloomingpresidentialelectionhelddownactivityasdeep-pocketedplayersawaitedabetterenvironmentforplacinghigher-priced

bets.BiopharmaM&Aisexpectedtorebound

in2025andtheyeargotofftoahotstartwhenJohnson&JohnsonagreedtobuyIntra-Cellularfor$14.6bnon13January,nearlytriplingthepricetagofthelargesttakeoutrecordedduring2024,

Vertex’s$4.9bnpurchaseofAlpineImmunein

April.ThebiopharmasectordidnotevenapproachapurchaseofthatsizeduringQ4,asH.Lundbeck’s$2.6bnacquisition

ofLongboardPharmaceuticalsendedupthehighest-valueddealannouncedinthe

finalthreemonthsof2024.Itwasoneofjustthreeacquisitionsvaluedat$1bnorhigherduring

Q4.Thefirstquarterof2024

provedanoutlier,astheindustrymade54

M&Atransactionswithatotalvaluationofnearly$37bn.Thatvaluationnearlyequaledtheslightlylessthan$40bninacquisitionsrecordedoverthefinalninemonthsof2024,butNovoHoldings’$16.5bnacquisitionof

Catalent–amanufacturing-drivendealexpectedtobenefitNovoNordiskbyaddressing

itssupplyissuesforsemaglutide-containingproductssuchasOzempicandWegovy–skewedtheQ1dollartotal.The

transactionwasbiopharmaceutical-adjacent,butnotstrictlyapure-playbiopharma

deal.Thebiopharmasectordid

notapproachtheQ1dealvolumeorvaluationtotalsduringtheremainderof2024,althougharelativelyhealthy38takeoutsvaluedatslightlymorethan$20bnwererecordedduringthesecondquarter.In

Q3,

acleardeclineinM&Aactivitywas

evident–whiletherewere29M&A

transactions,totalvalueonlyreached

$10.5bn.M&A

Values

Continued

To

Decline

During

Q4

2024Evaluatedatashowthatthebiopharmaindustrymade$9.5bnofacquisitionsduringthefourthquarter,a

thirdconsecutivequarterofdecline,althoughdealvolumeroseto33fromQ3’s

29.Biopharma

M&A

is

expected

to

rebound

in

2025.Thefourthquarterof2024reversedatrendseeninthepriortwoyears,whenM&Aactivitysurgedduringthefinalthreemonthsoftheyear.InQ42023,thebiopharmasectormade49M&Adealsvaluedatmorethan$52bn,highlightedbyapairof$10bn-plustakeouts,andin

2022,thefinalquarter’stotalsof48acquisitionsvaluedatmorethan$37bnmadeforthebusiestquarterofthat

year.Lundbeck’sInterestIn

EpilepsyLeadsQ4M&ADenmark-headquarteredLundbeck

madethelargestdealofthefourthquarter,agreeingtopay$2.6bnon14OctobertoacquireLaJolla,CA-basedLongboard,mainlytogetitshandsonbexicaserin,anext-generation5-HT2Creceptor

agonistthatisbeingstudiedin

seizuredisorderssuchasDravetsyndrome

(DS),Lennox-Gastautsyndrome(LGS)andotherdevelopmentalandepilepticencephalopathies

(DEEs).LastSeptember,thecandidateentered

aPhaseIIIstudyinDravetsyndrome,

anindicationithasbreakthroughtherapydesignationforfromtheUSFoodandDrugAdministration.AccordingtoEvaluatePharma,thedrugisontrack

tolaunchinlate2028,withapeakrevenueprojectionof$850min2030.Lundbeckclosedthedealon2December,

paying$60pershareforthebiotech,a70%premiumtoLongboard’s10-day

averagesharepricebeforethedealwasannounced.Thequarter’ssecond-largestdealwasAbbVie’s$1.4bnbuyoutof

AliadaTherapeuticson28October,bringing

theNorthChicagofirmALIA-1758,aPhase

IThefourthquarterof2024reversedatrendseeninthepriortwoyears,whenM&A

activitysurgedduringthefinalthreemonthsoftheyear.bispecificantibodycandidateforAlzheimer’sdiseasethattargetspyroglutamateamyloidbeta(3pE-Aβ),thesametargetasLilly’sKisunla

(donanemab),butwithpotentiallybettertargetingandotheradvantages.Thetransactionclosedon11

December.AbbViealsomadethefifth-largestacquisitionofQ4,paying$200mon13DecembertoacquireWisconsin-headquarteredNimbleTherapeutics,a2019spinoutfromRoche,withaspecializedtechnologytochemicallysynthesizescaffoldednaturalandmodifiedmacrocyclicpeptidomimetics–fromalibraryofphotoprotectedaminoacids–formultipletherapeuticareas.

Thedeal,whichincludesthepotentialofearnoutstoNimbleshareholders,

broughtAbbViethebiotech’splatformtechnologyaswellasitsleadcandidate,anoralpeptideIL23Rinhibitorinpreclinicaldevelopmentfor

psoriasis.Rocheaddedtoitscancerpipelineon26Novemberbypaying$1bnupfront,withupto$500minearnoutspossible,forcelltherapyspecialistPoseida.Thetwocompanieshadbeenpartneredsince2019ondevelopingoff-the-shelf

chimericantigenreceptorT-cell(CAR-T)therapies,withaninitialfocusonmultiplemyeloma.Stillnotclosed,thedealwasstructured

sothatshareholdersintheSanDiegobiotechget$9pershareupfrontandpotentialtorealizeupto$4pershareinmilestone

payments.Germany’sBioNTechagreedon13NovembertoacquireBiotheus,adeveloperofbispecificantibodies,

for$800mupfrontplusupto$150minearnouts.BioNTechhadlicensedtheChinesefirm’sBNT327(also

PM8002),oneofthemostadvancedPD-(L)1xVEGF-Abispecificcandidates,inJuly2023.BNT327itselfisyettoenterPhaseIII,butBioNTechsaidduringaQ3investorpresentationthatitplannedtoinitiateaPhaseII/IIINSCLCtrialinnon-smallcelllungcancerandaPhaseIIItrialin

small

cell

lungcancerbytheendof2024,withaPhaseIIIstudyintriple-negativebreastcancerplannedforthefollowing

year.Clickhereorpressenterfortheaccessibility

optimisedversionModest

FinalQuarterCompletesShakyBiotechIPOComebackFor

2024Septernaisthebestperformer

ofnewlylaunchedfirmsfromQ4,withmoreinitialpublicofferingsfueledbypotentialinterestratecutshopedforin

2025.BiotechIPOsstagedamoderate

recoveryin2024butamutedendtotheyearshowedhowfragilethemarketremainsforcompanieslookingto

launch.Fullyeardatashows26companiesdebutedonUSexchangeslastyear,higherthanthe21achievedin2023and22in2022,whenapandemic-fueledboominbiotechflotationsabruptlyended.Howeverthemarketisno

surefireroutefornewbiotechslookingtoacceleratetheirbusinessplansandthefinalquarterof2024sawjustfourcompaniescompleteanIPO,raisingatotalof

$670m.Lukewarminvestorsentimentforthewholesectorisundermining

performanceforpost-IPObiotechs,withmanylaunchedinthelastfewyearstrading

wellbelowtheirlaunchvalues.Thisappliestothemostrecentadditions,withthree

ofthefourlaunchedinthefinalquarter–UpstreamBio,JupiterNeurosciences

andCAMP4Therapeutics–currentlytradingata50%discounttotheirlaunchprices.(see

table).Standingoutfromthiscohortis

Septerna,whichraisedthemostcapital($331m)

anditsshareprice($19.30on23January)isonly9%lowerthanitslateOctober

launchprice.TheSouthSanFrancisco,

CA-basedcompanyisdevelopingnextgenerationoralsmallmoleculeGPCRtherapiesanditsleadcandidateisSEP-786,aPTHreceptoragonistfor

hypoparathyroidism.Modest

Final

Quarter

Completes

Shaky

BiotechIPOComeback

For2024SepternaisthebestperformerofnewlylaunchedfirmsfromQ4,withmoreinitialpublicofferingsfueledby

potentialinterestratecutshopedforin

2025.Thereisa

considerablebacklogofprivatebiotechcompanieslookingtolaunch

IPOs.CurrentlyinaPhaseIstudy,the

companyisexpectingtoshareinitialresults

bymid-2025.ResearchbyanalystsatJefferiesshowsthereisaconsiderablebacklogof

privatebiotechcompanieslookingtolaunchIPOs,withmanyawaitingmorefavorablemacro-economicandbiotechmarketconditions.InterestRatesAnd

TrumpAdministrationChiefamongthemacrofactorsisthe

USinterestrate,andtheFederalReserve

hasindicatedthatitmaycontinuetocuttheratein2025,aslongasinflationremainsundercontrolanddownfromits2022peak.InDecember,theUScentralbank

lowereditspolicyratetoa4.25%-4.50%range,withexpectationsoftwofurtherrate

cutsthisyear,withthefirstpotentiallyarrivinginMarch.ThenewTrumpadministrationhaspromisedabroadandwide-rangingset

ofpolicychanges,theimpactofwhichremainshardtoread.Thesewillincludemacro-economicpoliciessuchastariffsoncertainimportsandatthesectorlevel,effortstoshakeupregulation,includingthelikelyappointmentofpharmaindustryskepticRobertF.KennedyJnrattheDepartmentofHealthandHumanServices.Lacklusterinterestinsmall-to-mediumbiotechwasdemonstratedbythe

overallflatperformanceofthesector-specificXBIexchangein2024,which

showedvirtuallynogrowthoverthe12months.Thiswasincontrasttoacontinuing

boomintechcompanystocks,whichhelpedraisetheDowJonesby16%last

year.Nevertheless,thereissomeoptimismaboutabouncebackinthebiotech

sectorin2025,withthehopedforinterestratecutspotentiallycombiningwith

higherM&Aactivitytostimulatethe

sector.OntheIPOfront,fourcompanieshavealreadydeclaredtheirintentiontofloatinearly2025:cysticfibrosis-focused

Sionna,autoimmuneandinflammatoryconditionscompanyOdyssey,precisionmedicinesfirmMazeTherapeuticsandobesityspecialistsMetsera.There

is

some

optimism

about

a

bouncebackin

the

biotech

sector

in

2025.Clickhereorpressenterfortheaccessibility

optimisedversionBiopharmaVCFundraisingReachedHighest

TotalSince

2021EvaluatePharmadatafromthefourthquarterof2024showanotherperiodofventure

capitalfundraisingthatbeateachquarterof2023,as$100m-plusmega-rounds

surged.Venturecapitalfundraisingbybiopharmaceuticalcompaniesrose

to$7.11bninthefourthquarterof2024,

afterfallingto$6.46bninQ3from$7.95bninQ2,accordingtodatafromEvaluate.Buttheyearhasshownasignificantrebound.BytheendofQ3,the2024fundraisingtotalalreadyexceededthefull-year2023totalof$19.61bn,andwiththeQ4datainhand,venturefundraisinglastyear

totaled$28.05bn,alsobeatingthe

$27.27bnraisedbydrugdevelopersin

2022.Eachquarterof2024exceededeachofthequartersin2023,drivenbyasurge

inVC

mega-roundsof$100mormore.Evaluate’sdatashowthatVC

financingsinthe$100m-pluscategory

totaled$3.79bn-$5.25bnduringeachofthefourquartersof2024,butthequarterly

mega-roundtotalsexceededthoselevels

duringonlyfourquartersbetweenQ12020andQ42023.Thelastquarterof2024includedfinancingsfortwocompaniesthatraised$400mormoreinventurecapital–TreelineBiosciencesandKaileraTherapeutics.(See

table

alongside

for

Q4’s

top

five

VCfinancings.)With

Q4

Data

In,

Biopharma

VC

FundraisingReached

Highest

Total

Since

2021EvaluatePharmadatafromthefourthquarterof2024showanotherperiodofventurecapitalfundraisingthatbeat

eachquarterof2023,as$100m-plusmega-rounds

surged.Eachquarterof2024exceededeach

ofthequartersin

2023.Meanwhile,the$1.32bninventureroundsof$50morlessandthe$1.79bninVCrounds

of

$50m-$100m

in

Q4

of

this

yearwerethebiggestquarterlytotalsforthetwocategoriesin2024.However,thequarterlytotalforVCfinancingsof$50mor

less

exceeded

the

Q4

2024

level

during12oftheprior19quarters,whilesevenquartersexceededtheQ42024totalforfinancingsof

$50m-$100m.Theshiftofventurecapitaltolargerfinancings,usuallyforlater-stagecompanies,isareflectionofthecurrentcapitalmarketsenvironmentinwhichinvestorsarelesslikelytoinvestinriskieropportunities,suchasearly-stagedrugdevelopment,whileinterestratesare

high.VC

andpublicmarketinvestorsarefavoringcompanieswithclinical-stagedrugcandidatesintherapeuticareas

suchasobesityandcardiovasculardiseases,neuroscience,targetedoncologyandimmunology.Ifmergersandacquisitionscontinue

atthepaceandscaleseenearlierin

January–withJohnson&JohnsonbuyingIntra-CellularTherapiesfor$14.6bn,GSK

payingupto$1.15bnforIDRxandEliLillycommittingupto$2.5bnforScorpionTherapeutics–thatmayboostinvestorconfidenceinbiopharma

opportunities.Evenstart-upscouldbenefitfromsimilarbusinessdevelopmentactivity,sinceIDRx’sandScorpion’sleadprograms

wereinearlyclinicaldevelopment,andBigPharmacompaniescontinueto

seekpartnershipsatthepreclinical

stage.The

top

five

VC

financings

in

Q4

of

2024reflectthetherapeuticareasofgreatestinteresttobothBigPharmabuyersandinvestors–obesity,targetedcancertherapiesand

neuropsychiatry.TreelineBioscienceshasbeenquiettodateaboutitstargetedcancerdrugpipeline,butthecompanydisclosedinaFormDfiledwiththeUSSecuritiesandExchangeCommission(SEC)inOctoberthatitraised$421.8m,whichfollowed

twopriorFormDfilingswiththeSECthatexceeded$200meachin2021and

2022.Kaileraburstontothesceneatthestart

ofQ4witha$400mseriesAroundtofunditspipelineofobesitymedicines,

includingfourdrugslicensedfromHengrui–theGLP-1/GIPdualagonist

HRS9531(KAI-9531),theoralGLP-1

agonistKAI-7535,anoraltabletformulationofKAI-9531andthepreclinical

GLP-1/GIP/glucagonreceptoragonist

KAI-4729.KaileraandHengruireported

positivePhaseIIdataforKAI-9531earlierthismonth.TheteambehindKarunaTherapeutics–thedeveloperofthenewlyapprovedschizophreniadrugCobenfy

(xanomelineandtrospiumchloride),whichBristolMyersSquibbacquiredfor$14bn–launchedSeaportTherapeutics

with$225minseriesAfundinginOctober.SeaportwilluseitsinitialfundingtoinitiateaPhaseIIbclinicaltrialforleaddrugcandidateSPT-300inmajordepressivedisorderandbeginclinicaldevelopmentofSPT-320for

generalizedanxiety

disorder.Metseraraised$215minseriesBfinancinginNovemberafterit

closeda$290mseriesAroundinApril,bringingits2024venturecapitalhaulto$505m.TheproceedswillfundaPhaseIItrialoftheonce-monthlyinjectableGLP-1receptoragonistMET-097ithatthecompanyinitiatedlatelastyearaswellasongoingPhaseItrialsofMET-233i,an

ultraVCandpublicmarketinvestorsarefavoringcompanies

with

clinical-stage

drug

candidates

intherapeuticareassuchasobesityandcardiovasculardiseases,neuroscience,targetedoncologyand

immunology.long-actinginjectableamylinanalog,andMET-002,anoralGLP-1receptor

agonist.Inthetargetedcancerdrugspace,

AlentisTherapeuticsraised$181.4m

inNovembertofunditspipelineofClaudin-1positive(CLDN1+)

antibodiesandantibody-drugconjugates.The

Swissfirm’sseriesDroundalsowillsupportitsCLDN1+ADCprogramforfibroticdiseases.For

more

on

what

2025

will

hold

for

pharma,

check

out

our2025Preview

Report.Clickhereorpressenterfortheaccessibility

optimisedversionMid-CapBiopharma’sBiggestWinners

AndLosersOf2024SummitTherapeuticshitthestockmarketheightsin2024,alongwithahandfulof

biotechwithnoveltherapiesandplatforms,whileModernawasdraggeddownbyshrinkingCOVID-19vaccine

sales.Lastyearwasfarfromvintageforthebiotechsectorintermsofstockperformance:theS&PBiotechnologySelect

Industry

Index

rose

by

only

3%in2024,andlaggedfarbehindthe25%achievedbytheS&P500andbigtechfirms,whichhitrecord

highs.Nevertheless,therewereafew

starperformers–andnotjuston

USexchanges.EvaluatePharmahas

compiledatop10ofthebest-performingstocksacrossmid-capcompanies,aswellasthetenfirmsthatsawtheirstocksinkthemostoverthe12-month

period.ClaimingtheprizeofbiggestsharepriceincreasewasSummitTherapeutics,whichsawitsmarketcapgrowsixfold.ItsstockwentthroughtheroofinSeptember

whenitspartnerAkesounveileddatafromtheHARMONi-2trialofitsdualPD-1/VEGFinhibitor,ivonescimab,infirst-linenon-small-celllungcancer

(NSCLC).Ivonescimabbecamethefirstdrug

toachieveclear

progression-freesurvivalsuperioritytoMerck&Co’santi-PD1,Keytruda(pembrolizumab),inthissetting.SummitmustnowreplicatethesuccessofthisChina-basedPhaseIIIstudywith

aglobal/USone,andinvestorsareconvincedthatitsmanagementteam–whichpreviouslyworkedtogetheratviaPharmacyclicstobringBTKinhibitoribrutinibtomarketwithJ&Janda$21bnbuyoutbyAbbVie–canachievesuccessagain.ItisnotablethatAkeso,listedontheHongKongexchangeand

holdingtheChinarights,didnotenjoythesamemagnitudeofuplift,itssharesrisingbyonlyaround50%overtheyear,underliningtheimportanceoftheUSmarketandUSinvestorsinfueling

biotechstocks.InsecondplaceisJanux,whichsawitssharestakeoffwithhighlypromising

dataMid-Cap

Biopharma’s

Biggest

Winners

And

LosersOf

2024SummitTherapeuticshitthestockmarketheightsin2024,alongwithahandfulofbiotechwithnoveltherapies

andplatforms,whileModernawasdraggeddownbyshrinkingCOVID-19vaccine

sales.Lastyearwasfarfromvintageforthebiotechsector

in

terms

of

stockperformance.Claimingtheprizeofbiggestsharepriceincreasewas

SummitTherapeutics.fromitsinprostatecancer

treatment,JANX007.WhiletherearemanycompanieslookingtodevelopT-cellengagerantibodydrugs,Janux’sdrugcouldbebest-in-classforsafetyandefficacy,basedonits

“masking”technologywhichblocksactivityagainsthealthy

tissue.Thecompanyisnowmoving

JANX007intoPhaseIbexpansiontrials,withupdatesexpectedin

2025.CanBayerStopThe

Rot?Onceaformidablebigpharma

player,Bayerhasbeendraggeddownbystrategicmisstepsandevaporatinginvestorconfidence.EffortsbyCEOBillAnderson

to

hack

away

at

dead

wood

atthecompanyhavenotyetinspiredrenewedconfidenceinthefirm,and

itssharesdeclinedbyawhopping25%

inNovemberafterthecompanywarnedaboutfuture

earnings.ManagementwillhopethattheexpectedUSapprovalofelinzanetantfor

vasomotorsymptoms(hotflashes)associatedwithmenopauseandmarketexpansionforitsprostatecancerdrug,Nubeqa(darolutamide),willbegintoturnthingsaroundin

2025.TheoutlookisperhapsevengloomierforModerna,whichwontheunenviable

prizeofthebeingthecompanywiththesteepestsharepricedeclinelast

year.Unfortunately,thattrendhasonly

continuedin2025,withitssharelosingafurther20%sofar,afteranalystsatMorganStanleysaidthefirm’sCOVID-19vaccinesrevenueswouldshrinkagain

thisyear.While

there

are

many

companies

looking

to

develop

T-cell

engager

antibody

drugs,

Janux’s

drug

could

bebest-in-classforsafetyand

efficacy.Othercompaniesonthelistwerelessvictimsoffundamentalproblemswith

thepipeline,andmoretheexcitablenatureofinvestorswhenabuyoutcouldbeinthemaking.LegendBiotechsawitssharepricerisesteeplyinthesummerwhenrumorsof

apotentialacquisitionbyitspartnerJ&Jemerged.However,whennooffermaterialized,theexcitementturnedtodisappointment,andLegendendedup42%downattheendof

2024.Beingoneitherthefastest-growingorfastestdecliningstocklistsmakesacompanyapotentialtargetforabuyout

–thoughoncontrastingvaluations–andanalystsexpectbigpharmatobemoreactiveinthisfieldthisyearthan

last.Beingonei