默沙东4亿3千万美元加盟Arvinas抢占蛋白药物开发新制高点

2015年4月8日讯/生物谷BIOON/--随着生物技术的发展，人类的药物开发早已不仅局限于化学药物。人体内成千上万种蛋白为科学家开发新药物提供了丰富的靶点库。不过，迄今为止研究人员在开发蛋白类药物时的思路仍主要是通过抗体和化学小分子阻断或是刺激相应的蛋白质靶点。有研究人员指出，在目前常用的20000种蛋白药物靶点中，只有不到四分之一能够使用这一策略。因此，开发新的蛋白质药物技术已经成为生物医药巨头竞相参与的一个热点。
最近，默沙东公司宣布和著名药物生产商Arvinas公司签订了一项价值4亿3千4百万美元的合作研发协议，旨在抢占这一领域的制高点。Arvinas公司独有的蛋白水解靶向嵌合体技术（PROTAC）可以通过激活细胞内部的蛋白降解途径定向降解某些”不“受欢迎”的蛋白质，从而将一个个细胞转变为药物单位。这一思路将有望在未来的蛋白质药物研发中大显身手。
根据合约规定，默沙东公司将向Arvinas公司支付包括预付款、研究经费以及相应的里程碑资金在内的共计4亿3千4百万美元的经费，作为回报，默沙东公司将获得PROTAC这一极具前景的新技术。不过合约双方并未透露此次研究涉及的靶点。
成立于2013年的Arvinas公司由于其PROTAC技术而迅速为业内所熟知，公司的这项技术来源于耶鲁大学CraigCrews教授的实验室。公司CEOMannyLitchman称此次合作为Arvinas公司进一步明确自己未来定位起到了重要作用，而他也相信公司的PROTAC技术将成为未来默沙东药物开发系统中的一个重要卖点。目前公司正在利用这一技术开发相应的肿瘤治疗方案，公司希望于明年年中向FDA申报这一治疗方案。
详细英文报道：
Merck($MRK)haspartneredupwithfast-movingupstartArvinastogetitshandsontechnologythatpromisestogivedrugdevelopersacrackatsomepreviouslyuntouchabletargets,usingthebodysnaturalgarbagesystemtodumptroublesomeproteins.
Underthedeal,MerckwillhandtheNewHaven,CT,biotechanup-frontpaymentandresearchfunding,promisingmorecashtiedtodevelopmentmilestonesandsettingArvinasmaximumhaulat$434millionifeverythingworksoutoverthemultiyearagreement.Inexchange,Merckwillgetachancetousethecompanysproteolysis-targetingchimera,orPROTAC,technology,whichcreatessmall-moleculetreatmentsthatmarkproteinsfordegradation.
BasedonworkoutofCraigCrewsYaleUniversitylabs,PROTACtreatmentsaredesignedtogetridofunwantedproteinsbytriggeringacellsnaturalclean-upsystem,markingtargetsforremovalandlettingthebodysdegradationmechanismsdotherest.Arvinas,launchedin2013,haslargelyfocuseditsinternaleffortsononcology,buttheMerckdealspansmultiplediseasetargetsinanundisclosedarrayoftherapeuticareas,thecompanysaid.
Themajorityofprotein-targetingtherapeuticsinthemarketorindevelopmentworkbyeitherinhibitingorboostingtheirtargets,whetherviaantibodiesorsmall-moleculechemicals.Butonlyaboutaquarterofthebodysroughly20,000proteinscanbeeffectivelydruggedthatway,ArvinasCEOMannyLitchmansaid.Byattackingproteinsfromwithintheirhomecells,however,Arvinastechnologycanpotentiallyopenupnewavenuesoftherapeuticdevelopment,hesaid,exposingsomelong-untouchabletargetstoguideddegradation.
ThatpotentialwasamajorsellingpointforMerck,Litchmansaid,andnowitsonArvinastodemonstratethatitstechnologycancomethroughintheproof-of-conceptstage,rollingintowhattheCEOexpectstobe"atruecollaboration."Merckhastheoptiontoexpandthedealtoincludemorediseasetargets,triggeringanundisclosedpayment,andLitchmanbelievestheagreementcouldcreateamodelforArvinasfuturepartnerships.
ThecompanyhasheldontoahostofinternalprogramsalsobasedonPROTAC,includingaleadoncologyassetArvinasexpectstogetintotheclinicinthemiddleofnextyear.Thebiotechwilllikelylooktoinkoneortwomoredealsalongtheway,Litchmansaid,atoncecautiousnottospreaditselftoothinandoptimisticthatMercksbigco-signwillhelpitbringwould-bepartnerstothetable.
"IthinkwhenacompanylikeMerckhasdonedeepduediligence,surveyedthecompetitivelandscapeandselectedArvinasasthebestplatformoutthereforproteindegradation,thatsasignalforotherswevetalkedtothatperhapsadeeperdivemaybewarranted,"Litchmansaid.
Arvinasgotrollingwitha$15millionAroundfromCanaanPartnersand5AMVentures,licensingCrewstechnologyandassemblingateamofinvestigatorstopushitforward.ThebiotechquicklymovedtoestablishpreclinicalproofofconceptforPROTAC,recruitingLitchman,an18-yearNovartis($NVS)veteran,intimetostartshowingofftheplatformatJanuarysJPMorganHealthcareconference.

医药网新闻