feature B2 antibody Following on from thesuccess antibodies in oncology, of monoclonal analysts big sales predict from conjugates antibody–drug missiles: Guided Evaluate Ltd, www.evaluate.com lymphomaandanaplasticlarge celllymphoma with Hodgkin by Genetics/Takeda’s Seattle Analysts predictthat itwillbeovertaken Adcetris (brentuximab vedotin) treat some patientswithbreast cancer, iscurrently leadingtheantibody Figure forecasts 1:Sales for antibody selected conjugates (ADCs).popular platform: antibody–drug Here, for we analyze another thecommercialofdealmaking impact this timelastyear ( antibodies designed featured to target antigensatonce—was two therapies. Oneofthemostwidelypursuedplatforms—bispecific explore approaches to enhancetheeffectiveness ofantibody-based and cancer. by Motivated thissuccess, companiesare continuingto diseases drugs owing to theirtherapeuticeffects ininflammatory antibodies (mAbs)dominate thelistofbest-sellingMonoclonal BioPharma Dealmakers
|September 2017| Sales (US$ millions) 1200 1400 1600 1800 1000
(brentuximab vedotin) 200 400 600 800 0 –
Adcetris drug conjugates, whileadvances in the underlying platforms continue to drive dealmaking. BioPharma Dealmakers biopharmadealmakers.nature.com
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with salesof$1.8billion in2022.Source: EvaluatePharma, July2017, Glembatumumab Roche’s (trastuzumabemtansine), which isapproved to Kadcyla – antigen (typically one that is selectively expressed on the surface expressed onethatisselectively onthesurface antigen (typically to cancer cells. cellsto beadministerednormal alone canbedelivered selectively of itspayload. thisway, In anticancerdrugsthatare fartoo toxic to cancer cellsspecifically, where itisinternalized, leadingto therelease the goalisfor of themAbto deliver thecytotoxic drugto thesurface thetwo. between chemical linker For oncologyapplicationsofADCs, ahighlycytotoxic drug),anda (typically of cancercells),awarhead
million. withsales in2016of~$840 million. drug conjugate market, vedotin ADCs consist of three components: a mAb specific for a particular
Besponsa — Nature Reviews |DrugDiscovery Mirvetuximab approved for treating patients soravtansine
Vadastuximab
talirine 2022 2019 2016
markusblanke/iStock/Thinkstock emtansine) for HER2‑positive metastatic breast cancer. Both are FDA approval (trastuzumab for itsHER2‑targeted ADCKadcyla lymphoma. anaplastic large-cell Two years later, received Roche (brentuximab lymphomaandrelapsed vedotin) for systemic Hodgkin and DrugAdministration (FDA) for itsCD30‑targeted ADCAdcetris with in partnership Takeda, received approval from theUSFood a deeppipelineindevelopment ( approval,regulatory ( withseveral alsocloseto market ADC platforms have matured sufficientlyfor multipleADCsto gain the 1960s, butitisonlyinrecent years thatthecomponentsof lenging. Research ontheADCconcepthasbeengoingsince EvaluatePharma, July2017,Evaluate Ltd, www.evaluate.com Figure 2: The conjugate antibody–drug pipeline. provided for dealsupto July. Source: EvaluatePharma, July2017,Evaluate Ltd, www.evaluate.com FigureThe conjugates, 3: numberofantibody–drug by development stage, involved indealssince 2011.
Number of products involved in deals however, practice, In thisgoalhasbeenhighlychal achieving 10 15 20 25 30 35 40 45 0 5 (21%) Research project 3% (43%) Preclinical 2011 47% 23% 27% 30 products 455 Nature Reviews |DrugDiscovery Filed (0.2%) Marketed (3%) 3% Fig. 2 (19%) Phase 1 2012 ). In 2011, Seattle Genetics, 2011,Seattle ). In 74% 23% 31 (11%) Phase 2 3% Source: Source: Fig. 1 2013 20% 77% (3%) Phase 3 40 ) and - Year 3% DM4 is a component of mirvetuximab soravtansine,DM4 is a component of mirvetuximab all of which and batumumab vedotin, whileDM1isacomponentofKadcyla product, glem drug componentofAdcetris andanotherlate-stage cytotoxic the is MMAE maytansinoids DM1orDM4 andalinker). (consisting ofthe orImmunogen as thecytotoxic drugandalinker) ing ofanaurostatin analogsuchasmonomethyl E(MMAE) auristatin are basedontechnology (consist Genetics licensedby eitherSeattle manyIndeed, of the ADCs in the later stages of clinical development their own drugcandidates ( othercompaniesfor theirplatforms, multiple inadditionto pursuing companies intheADCfield ( nology platforms for ADCshave alsobeenthebasisfor many deals ADCproducts inoncology.value ofparticular techThe underlying 2016,isforecastedApril to beinsecond place. acquired through its$9.8 billionpurchase in (Rova-T), ofStemCentrx with salesof$1.8billion( Takeda’s to becometheleader, Adcetris willhave leapfrogged Kadcyla analysts atEvaluatePharma Genetics/ thatby predict 2022,Seattle status,to with sales in 2016 of ~$840 blockbuster lymphoblastic leukemia. approved inEurope Bcell–precursor for acute relapsed orrefractory Pfizer’s CD22‑targeted ADCBesponsa(inotuzumabozogamicin) was inmany too.now othercountries marketed AndinJuneofthisyear, interest inADCtechnologies. technology in2017alone linker ThioBridge upto $400millionaroundwhich hassigned its dealsworth two to $440millionin2013. Anddealssuchasthoseinvolving Abzena, of ADCsincludingrovalpituzumab tesirine pyrrolobenzodiazepines thatare usedasthecytotoxic component ple, AstraZeneca acquired Spirogen the pastdecade, leadingto deals. more For platform-driven exam strategies and/orcytotoxic drugcomponentshave alsoemerged in are highlighted in Fig. 3 This recent acquisitiondealindicates product thehighpotential The current highest-selling ADC,Roche’s isalready close Kadcyla, Other companiesthathave developed novel Other linkers, conjugation 2014 70% 27% 33 ) . Seattle Genetics andImmunogen Genetics . Seattle 7% 4% Figure 1 2015 58% 23% 26 8% Fig. 1 . Nat. Rev. Discov. Drug — Nature Reviews |DrugDiscovery ). AbbVie’s rovalpituzumab tesirine have signed licensingdealswith 4% 4% — 2016 a company thatdeveloped 57% 35% 23 *2017 data are only *2017 dataare only Development stages biopharmadealmakers.nature.com |September 2017 | — , — indicate the continued indicate thecontinued two of the pioneering ofthepioneering two in a deal valued at up in adealvaluedatup Preclinical Marketed Research projects Phase 1 Phase 2 Phase 3 16 million. However, 6% , 315–337; 2017). , 315–337;2017). 2017 15 40% 27% 27% - - - -
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