Cemdisiran

公众号：再生元是我最喜欢的医药公司，25年3季度电话会中有很多精彩内容。一是BCMA/CD3双抗、CD20/CD3双抗竞争力说的比以前更清晰了；二是26年和赛诺菲的开发余额补偿预计只有6亿美元，今年是大概是12亿美元；三是眼科新产品，四是超罕见疾病领域进展（再生元针对儿童失聪的药物获得了美国第一个国家优先评审券），当然还有C5、凝血等其他项目进展。25年有点对再生元流年不利，收到了两份CRL，公司对CRL也没遮掩，再生元董事长对CRL的问题也是直面问题，解释了很多。 以下是再生元2025Q3电话会中英文对照，百度翻译后本人稍加校对改动： LeonardSchleifer-Co-ChairmanoftheBoard,President,ChiefExecutiveOfficer,Co-FounderThanks, Ryan. Thanks to everyone for joining today's call. For my remarks today, I will summarize our third quarter top line performance, provide an update on EYLEA HD regulatory matters, briefly discuss our recent pipeline progress, and close with some comments regarding our discussions withtheUnitedStatesgovernmenttolowerdrugcostsforAmericanpatientswhilepreservinginnovation. 伦纳德·施莱弗 感谢大家参加今天的电话会议。在今天的发言中，我将总结我们第三季度的营收表现，介绍EYLEA HD监管事宜的最新进展，简要讨论我们近期在研产品线的进展，并在最后就我们与美国政府就降低美国患者药费同时保持创新的讨论发表一些看法。 I'llthenhandthecallovertoGeorge,whowillprovidemoredetailsonourpipelineprogress.Fromthere,Marionwillreviewourcommercial performance.Andfinally,Chriswilldetailourfinancialresultsandguidance. 接下来，我将把电话交给乔治，他将详细介绍我们的项目进展情况。之后，玛丽恩将回顾我们的商业表现。最后，克里斯将详细介绍我们的财务业绩和指导。 Regeneron delivered asolid third quarter driven by double-digit net sales growth for three of our leading products. Compared tothe third quarter of last year,worldwide net productsales for Dupixent increasedby 26% and Libtayo by 24% at constant exchange rates, while EYLEA HD in the United States grew by 10%. 得益于我们三款主打产品的净销售额实现两位数增长，再生元公司第三季度的业绩表现稳健。与去年第三季度相比，按固定汇率计算，全球范围内，度普利尤单抗（Dupixent）的净销售额增长了26%，Libtayo增长了24%，而美国市场上的EYLEA HD增长了10%。 RegeneronhadDupixentglobalnetsalesforthethirdquarter[of]$4.9billionasrecordedbySanofiwithstronggrowthcontinuingacrossapprovedindicationsingeographicregions.IntheUnitedStates,Dupixentnetproductsalesgrew28%comparedtothethirdquarteroflastyearwhilemaintaining its leadership position in both new to brand prescription share and total prescription share across all indications approved prior to thisyear. 赛诺菲记录显示，Regeneron第三季度dupi全球净销售额为49亿美元，在各地理区域的获批适应症中继续保持强劲增长。在美国，dupi的净产品销售额较去年第三季度增长28%，同时，在所有今年之前获批的适应症中，该药物在创新药新处方份额和总处方份额方面均保持领先地位。 Dupixent is now approved in the United States to treat eight distinct diseases driven by underlying Type 2 inflammation, including diseases of the skin, gut, and respiratory system, spanning age groups from infants to the elderly, and with more than 1.3 million patients globally being actively treated. Dupixent is one of the most widely used biologic medicines. Dupixent's approved indications could potentially address more than 4 million patientsintheUnitedStatesalone,positioningittoremainastronggrowthdriveroverthenear,medium,andlong-term. 度普利尤单抗现已在美国获批用于治疗由潜在2型炎症驱动的八种不同疾病，包括皮肤、肠道和呼吸系统疾病，覆盖从婴儿到老年人的各个年龄段，全球有超过130万患者正在接受积极治疗。度普利尤单抗是使用最广泛的生物药物之一。仅在美国，度普利尤单抗获批的适应症就可能惠及400多万患者，使其有望在近期、中期和长期内继续成为强劲的增长动力。 Global Libtayo net product sales were $365 million, up 24% on a constant currency basis compared to the third quarter of lastyear. In the US, net product sales grew 12%,whereLibtayo continues to be the market-leading immunotherapy for advanced non-melanoma skin cancers while building shareinlung cancer. 全球Libtayo的净产品销售额为3.65亿美元，按固定汇率计算，较去年第三季度增长24%。在美国，净产品销售额增长了12%，其中Libtayo继续作为市场领先的免疫疗法药物，用于治疗晚期非黑色素瘤皮肤癌，同时在肺癌治疗领域的市场份额也在增长。 Earlier this month, the FDA approved Libtayo in high-risk adjuvant cutaneous squamous cell carcinoma,making Libtayo the first and only PD-1 antibodyindicatedforthissetting.Whileitonlyhasbeenafewweekssinceapproval,ourlaunchisalreadyofftoagreatstart,andwelookforward totreatingtheupto10,000addressablepatientsintheUnitedStateswhocouldbenefitfromthismedicine. 本月早些时候，美国食品药品监督管理局（FDA）批准了Libtayo用于高危辅助性皮肤鳞状细胞癌的治疗，使Libtayo成为首个且唯一一个获批用于此适应症的PD-1抗体。虽然获批仅几周时间，但我们的上市工作已取得良好开端，我们期待为美国多达10,000名可及且能从该药物中受益的患者提供治疗。 MovingtoEYLEAandEYLEAHD.Affordabilityissuescontinuetodampenbrandedanti-VEGFcategorygrowth.AsannouncedinJune,weinitiatedamatchingprogramforupto$200millionincontributionstotheGoodDaysRetinalvascularandNeovascularDiseaseFund.ButIamdisappointed toreportthatthematching ofthirdquarterwasunder$1million due tothelackofdonationsfromotherpotentialcontributors.Weremain committedtomatchingfuturedonationstothisfundthroughtheendoftheyear. 转向EYLEA和EYLEA HD。可负担性问题继续抑制品牌抗血管内皮生长因子（VEGF）药物类别的增长。正如6月份所宣布的，我们启动了一项配套计划，为“美好日子视网膜血管和新生血管疾病基金”捐款高达2亿美元。但我很失望地指出，由于缺乏其他潜在捐助者的捐款，第三季度的匹配资金不足100万美元。我们仍致力于在年底前为该基金的未来捐款提供匹配资金。 Despite affordability headwinds, EYLEA HD had a strong performance in the third quarter,with US net product sales reaching $431 million, an all-timehigh,drivenbyrobustphysicianunitdemandgrowth,partiallyoffsetbyalowernetprice.Wecontinuetobelievethatfutureproductenhancements,suchas afour-weekdosing interval,theinclusion ofmacular edemafollowingretinal vein occlusion or RVO, andapre-filledsyringe administrationareneededtofullyunlockEYLEAHDcommercialpotential. 尽管面临可负担性方面的阻力，但EYLEA HD在第三季度表现强劲，美国净产品销售额达到4.31亿美元，创历史新高，这得益于医生用量需求的强劲增长，但部分被较低的净价所抵消。我们仍然相信，为充分释放EYLEA HD的商业潜力，未来产品需要改进，如采用四周给药间隔、纳入视网膜静脉阻塞（RVO）后的黄斑水肿，以及预充式注射器给药方式，。 Earlier thismonth, we were notifiedbyCatalent IndianaLLC, anaffiliateofNovoNordisk, thatthe FDAclassified their facilityas official action indicated or OAI.And to date, the issues identified during the July 2025 inspection have not been completely resolved. On that basis, the FDA issued a complete responseletter yesterday for the pre-filledsyringe supplemental BLA with the sole approvability issue relatingto unresolved inspectionfindingsatCatalent. 本月早些时候，诺和诺德（Novo Nordisk）的子公司Catalent Indiana LLC通知我们，美国食品药品监督管理局（FDA）已将其设施列为官方行动指示（OAI）。截至目前，2025年7月检查中发现的问题尚未完全解决。基于此，FDA昨日就预充式注射器补充性生物制品许可申请（BLA）发布了一封完整回复函，其中唯一涉及可批准性问题与Catalent未解决的检查发现相关。 We continue to execute on our previously announced plan to submit an application to add an alternate pre-filled syringe by January 2026 which wouldtriggerafour-monthFDAreview. 我们将继续执行之前公布的计划，即在2026年1月前提交一份申请，以增加一种替代的预充式注射器，这将触发美国食品药品监督管理局（FDA）为期四个月的审查。 We have also been diligently working with an alternate vial filler and have already submitted an application to include them in the EYLEA HD BLA withaPDUFAdatein lateDecember. Thiswould provideanadditionalopportunity fortheFDAto approvethesBLAforevery-four-week dosing inRVOgivenwebelievetherearenootheroutstandingreviewissuesforthisapplication. 我们还在努力与另一家药瓶灌装商合作，并已提交申请，希望将其纳入12月底有PDUFA日期的EYLEA HD BLA中。这将提供FDA批准每四周给药一次RVO的sBLA的额外机会，因为我们认为该申请没有其他未解决的审查问题。 Moving briefly toour pipeline which George will soon discuss inmore detail. We continue tomake significant investments in R&Dthathave yielded notable progress across several key programs. In just the past three months, we have announced positive Phase 3 or registration-enabling data forsixdistinctprogramsspanningimmunology,neurology,allergy,andrarediseases. 接下来，我们简要介绍一下我们的研发管线，稍后乔治将对此进行更详细的讨论。我们继续在研发方面进行重大投资，并在多个关键项目中取得了显著进展。仅在过去三个月里，我们就宣布了六个不同项目的III期临床试验或可用于注册申报的阳性数据，涉及免疫学、神经学、过敏症和罕见病领域。 Over the nextseveral months, welook forward torapidlyexpanding pivotal programs in hematology,oncology,thrombosis, obesity, andother metabolicdiseases,aswellasallergies,allofwhichwebelieverepresentanimpressivenextwaveofinnovativemedicinesdiscoveredordeveloped byRegeneron. 在接下来的几个月里，我们期待迅速扩大在血液学、肿瘤学、血栓形成、肥胖症和其他代谢疾病以及过敏症方面的关键项目，我们相信，所有这些项目都代表着由Regeneron发现或开发的令人印象深刻的下一波创新药物。 Finally,I'dliketotakeamomenttoaddressourongoingprogresstowardreachinganagreementwiththeUSgovernmenttohelplowerthecost of medicines for American patients. We are havingconstructivediscussions with the administration, andI'm pleased toshare that our priorities are closely aligned. 最后，我想花点时间谈一谈我们与美国政府就降低美国患者药品成本达成协议的持续进展。我们正在与政府进行建设性的讨论，我很高兴地告诉大家，我们的优先事项高度一致。 BothRegeneronandtheadministrationaredeeplycommittedtoensuringthatAmericanpatientshavetimelyandaffordableaccessto ground-breakingmedicalbreakthroughs. WelikewisesharethegoalofpreservingtheUnited States'positionas agloballeaderinbiotechinnovation andmanufacturing. 再生元和政府都坚定致力于确保美国患者能够及时且负担得起地获得突破性的医疗成果。我们同样也致力于维护美国在生物技术创新和制造领域的全球领先地位。 For more than a decade, George and I have argued that foreign governments have benefited fromAmerican innovation without sharing theburden ofitscost. Wearehopefultheeffortsofthisadministration canleveltheplayingfieldandconvincehighGDPnations tocontributetheirfairshare,ratherthanrelyingontheUnitedStatestoshoulderthevastmajorityofthisresponsibility. 十多年来，乔治和我一直认为，外国政府在从美国创新中受益的同时，却没有分担其成本负担。我们希望本届政府的努力能够创造公平的竞争环境，并说服高GDP国家贡献其应尽的份额，而不是依赖美国来承担绝大部分责任。 By addressing this imbalance, we can ensure a more equitable global system that supports continued advancements in medicine while improving affordabilityforUSpatients. 通过解决这种不平衡问题，我们可以确保建立一个更加公平的全球体系，在支持医学持续进步的同时，提高美国患者的可负担性。 Furthermore,weagreethatinvestinginUSmanufacturingisnotonlyvitalforcreatingjobsandstrengtheningoureconomy,butforsafeguardingnational security. In fact, in testimony before Congress in 2014, Regeneron highlighted the importance of prioritizing biotech manufacturing and innovationintheUnitedStates. 此外，我们一致认为，投资美国制造业不仅对创造就业机会和增强我国经济至关重要，而且对维护国家安全也至关重要。事实上，在2014年向国会作证时，再生元公司强调了优先发展美国生物技术制造和创新的重要性。 Regeneron has alreadymade significant commitments in this area, including our plans toinvest over $7 billion in infrastructure and manufacturing facilitiesinNewYorkandNorthCarolinaoverthecomingyears. 再生元已在这一领域做出了重大承诺，包括我们计划在未来几年内在纽约和北卡罗来纳州的基础设施和制造设施上投资超过70亿美元。 We remain optimistic about finding common ground with the administration that strikes the rightbalance between achieving our shared priorities whileadvancingRegeneron'smissionofharnessingthepowerofsciencetodeliverlife-changingmedicinetopatients. 我们仍然乐观地认为，我们能够与政府找到共同立场，在实现我们的共同优先事项与推进Regeneron利用科学力量为患者提供改变生命药物使命之间取得恰当平衡。 Inclosing,Regeneron'sbusinesscontinuestoperformwellwithimpressivecommercialexecution,drivingstrongfinancialresultsinthethirdquarter. Our pipeline is poised to deliver scientific breakthroughs that can potentially help treatmillions of patients and translate into meaningful commercialopportunities. Thecommercialteamremains focusedonmaximizinggrowth driversfrom ourinlinebrands,whilesuccessfullylaunching newproductsandindications.Finally,wecontinuetoprudentlydeploycapitalwiththegoalofdeliveringlong-termvaluetoshareholders. 最后，Regeneron的业务继续表现良好，商业执行令人印象深刻，推动第三季度取得了强劲的财务业绩。我们的研发管线有望带来科学突破，这些突破有望帮助治疗数百万患者，并转化为有意义的商业机会。商业团队将继续专注于最大化我们现有品牌的增长动力，同时成功推出新产品和新适应症。最后，我们将继续审慎配置资本，旨在为股东创造长期价值。 Withthat,I'llnowturnthecallovertoGeorge. 说完这些，我现在就把电话交给乔治。 GeorgeYancopoulos-Co-ChairmanoftheBoard,President,ChiefScientificOfficer,Co-Founder 乔治·扬科波洛斯 - 董事会联席主席、总裁、首席科学官、联合创始人 Thankyou,Len.Overthelastfewmonths,asLenjustmentioned,wehavedeliveredmultipleimportantdatareadoutsshowcasingthestrengthof our robust pipeline and the potential to drive future growth with positive pivotal data for Dupixent, for our C5 program, our cat and birch allergyprograms,aswellasinourrarediseaseprograms.Iwillalsoupdateprogressinoncology,anticoagulation,andotherprograms. 谢谢你，Len。正如Len刚才提到的，在过去的几个月里，我们发布了多份重要的数据报告，展示了我们的强大产品线实力以及推动未来增长的潜力，包括为Dupixent、我们的C5项目、猫和桦树过敏项目以及罕见病项目提供的积极关键数据。我还会更新肿瘤学、抗凝和其他项目的进展情况。 Starting with immunology and inflammation. Dupixentcontinues to deliver remarkable outcomesin addressing indications driven by Type 2 inflammation,potentiallyaddingtoits existing approvals foreight diseasesin theUnitedStates. We're anticipating theFDA's acceptance ofour submission for allergic fungal rhinosinusitis or AFRS in patients age 6 years and older based on positive data that we plan to present shortly. This representsyetanotherpotentialopportunityforexpandingDupixent'slabel. 从免疫学和炎症谈起。度普利尤单抗（Dupixent）在应对由2型炎症驱动的适应症方面继续展现出显著疗效，这可能为其在美国已获批的八种适应症再添新的适应症。基于我们计划不久后提交的积极数据，我们期待美国食品药品监督管理局（FDA）能批准我们提交的用于6岁及以上患者治疗过敏性真菌鼻窦炎（AFRS）的申请。这为度普利尤单抗的适应症扩展提供了又一个潜在机会。 Moving to our IL-33 antibody, itepekimab, which was studied in COPD for which it met its primary endpoint in one of two replicate Phase 3 trials, we and Sanofi are contemplating anotherPhase 3 trial for itepekimab in COPD, pending feedback from regulators.Itepekimab development is also advancing other respiratory diseases, most notably our ongoing Phase 3 studies in chronic rhinosinusitis with nasal polyps, where our genetic evidenceis compelling. 接下来谈谈我们的IL-33抗体——itepekimab，该抗体在慢性阻塞性肺疾病（COPD）研究中，在两项III期试验中，一项均达到了主要终点。我们和赛诺菲公司正在考虑针对itepekimab在COPD领域开展另一项III期试验，目前正在等待监管机构的反馈。itepekimab也在推进其他呼吸系统疾病的治疗开发，最值得注意的是我们正在进行的慢性鼻窦炎伴鼻息肉的III期研究，我们的遗传学证据非常有力。 Movingto our innovativeand multi-prongedallergy programs.Aspreviously announced,our Phase3 studiesof ourantibodiesfor catallergy andfor birch allergy have yielded statistically significant and clinically meaningful outcomes on primary and key secondary endpoints. These results represent the first proof of principle that targeting allergens with highly specific monoclonal antibody cocktails can achieve improvements in both ocularitchandredness. 接下来，我们介绍创新且多管齐下的过敏治疗方案。如之前所宣布，我们针对猫过敏和桦树过敏的抗体III期研究在主要和关键次要终点上均取得了具有统计学显著性和临床意义的结果。这些结果首次证明了用高度特异性的单克隆抗体鸡尾酒靶向过敏原可以改善眼部瘙痒和发红症状。 Importantly, in prior clinical trials, our cat and birch allergy approaches have delivered impressive and durable therapeutic benefits across nasal, respiratory,andskinallergysymptoms.Inthecomingmonths,weplantopresenttheseresultsatanupcomingmedicalmeetingandinitiateconfirmatoryPhase3studiesfortheseprograms.IntheUSalone,thesetherapiescouldhelpapproximately1.6millionpeoplesufferingfromsevere cat allergies andthe approximately1.4millionpeople sufferingfrom severebirchallergies. 重要的是，在之前的临床试验中，我们的猫和桦树过敏治疗方法在缓解鼻部、呼吸道和皮肤过敏症状方面展现出了显著且持久的治疗效果。在未来几个月，我们计划在即将召开的医学会议上展示这些成果，并启动这些项目的确证性III期研究。仅在美国，这些疗法就有可能帮助约160万严重猫过敏患者和约140万严重桦树过敏患者。 Regarding ourinnovative severe food allergy program, enrollment and dosingare progressingwellinoursmall proof-of-concepttrialcombining linvoseltamaband Dupixent. The first three patients have responded remarkably with greater than 90% rapid reductions in the allergy-causing immunoglobulinElevelsfollowingashortcourseoflinvoseltamabtreatmentwhicharethenmaintainedandcontinuetodecreasewithongoingDupixentmaintenance.Fullenrollmentofthissmallinitialstudyisstillexpectedoverthenextfewmonths. 关于我们创新性的重度食物过敏项目，在我们linvoseltamab和Dupixent联合用药的小型概念验证试验中，入组和给药进展顺利。前三名患者在接受短暂的linvoseltamab治疗后，对引起过敏的免疫球蛋白E水平迅速降低了90%以上，效果显著，随后在持续的Dupixent维持治疗中，这些水平保持不变并继续下降。预计在未来几个月内，这项小型初步研究将完成全部入组。 Basedoninsightsgainedfromtheprogramssofar,weareadvancingthedevelopmentofnext-generationagentsdesignedtospecificallyand safely deplete allergy-causing plasma cells, the first of which is expected to enter clinical trial next year, alongside several other promising novel candidatesinimmunologyandinflammation. 基于迄今为止从项目中获得的见解，我们正在推进下一代药物的开发，这些药物旨在特异性且安全地消耗引起过敏的浆细胞，其中第一种药物预计明年进入临床试验阶段，此外还有几种在免疫学和炎症领域有前景的新型候选药物。 MovingontooncologyandstartingwithLibtayo,whichwasrecentlyFDAapprovedasthe first andonlyimmunotherapyfor adjuvanttreatment ofhigh-riskcutaneous squamouscell carcinoma followingsurgeryandradiation basedon the onlysuccessful clinical trialin this setting, the C-POST trial data thatshowed a notable 68% reduction in risk of disease recurrence or death. This approval expands and extends Libtayo's leading position innon-melanomaskincancers. 接下来谈谈肿瘤学，从Libtayo开始。Libtayo最近获得FDA批准，成为首个且唯一一个用于高危皮肤鳞状细胞癌术后和放疗后辅助治疗的免疫疗法，该批准基于该领域唯一成功的临床试验——C-POST试验数据，该数据显示，该药物可将疾病复发或死亡风险显著降低68%。此次批准进一步巩固和扩大了Libtayo在非黑色素瘤皮肤癌治疗领域的领先地位。 Movingtofianlimab,ourLAG-3antibodystudiedincombinationwithLibtayo,ourpivotaltrialinmetastaticmelanomaisongoingwith enrollment forourprogression-freesurvivalcohortcompletinglastJanuary.Andresultsarenowanticipatedinthefirsthalfofthecomingyearduetoslowerratesofeventaccrual. 接下来是fianlimab，这是我们研究的LAG-3抗体，与Libtayo联合使用，这是我们在转移性黑色素瘤领域的关键试验，目前正在进行中，无进展生存期队列的入组工作已于去年1月完成。由于事件累积速度较慢，预计结果将在明年上半年公布。 Lynozyfic, our BCMAxCD3 bispecific has been approved in the United States and the EU for relapse refractory multiple myeloma. Lynozyfic has the potential for best-in-class efficacy in this late line setting compared to the other approved BCMAxCD3 bispecifics, with almost double the rates of completeresponsesasreportedintherespectivelabel. 我们的BCMAxCD3双特异性抗体Lynozyfic已在美国和欧盟获批用于治疗复发难治性多发性骨髓瘤。与其他已获批的BCMAxCD3双特异性抗体相比，Lynozyfic在这一晚期治疗场景中具有同类最佳的疗效潜力，其完全缓解率几乎是其他药品相应说明书中报告的两倍。 This isthe basis forourenthusiasm forstudying Lynozyficinearlier lines ofmyelomaandeveninprecursor settings, as amonotherapyor inlimited combinations. 这是我们对于Lynozyfic在骨髓瘤早线治疗甚至前体细胞环境中的研究感到乐观基础，无论其是作为单一疗法还是有限组合疗法。 Consistent with this, we've recently presented promising Phase 2 results in high-risk smoldering myeloma patients with Lynozyfic monotherapy, demonstratinga100%objectiveresponseratesin19evaluablepatients,withallsixpatientswhohavebeenfollowedforatleastoneyearachievingamolecularcompleteresponse. 与此一致，我们最近公布了采用Lynozyfic单药治疗高危隐匿性骨髓瘤患者的二期试验结果，显示19名可评估患者中客观缓解率达到100%，且随访至少一年的6名患者均实现了分子学完全缓解。 APhase3head-to-headstudyagainstDarzalexisplannedtostartinthecomingmonthswithDarzalexhavingdemonstrateda9%completeresponserateinthissetting.Inaddition,wehaveobservedrapidnormalizationwithLynozyficmonotherapyinpreviously-treatedlightchain amyloidosispatients,includingpatientswhohavepreviouslyreceivedandfailedtheDarzalex-containingcombinationchemotherapy. 计划在未来几个月内启动一项针对Darzalex的III期直接对比研究，Darzalex在此类患者中显示出9%的完全缓解率。此外，我们还观察到，在既往接受过治疗的轻链淀粉样变性患者中，单用Lynozyfic治疗可迅速实现正常化，其中包括那些既往接受过含Darzalex的联合化疗但失败的患者。 Finally,IwouldliketohighlightthatLynozyfichasdemonstratedan83%overallresponserateasamonotherapyinnewlydiagnosedmultiplemyeloma patients with responses deepening over time. Updated results will be reported at a medical meeting later this year. All together, these datagiveusconfidenceintermsofpursuingLynozyficasamonotherapyorinsimplifiedcombinationinearlylineandprecursorsettingsof myeloma. 最后，我想强调的是，Lynozyfic作为单一疗法在新诊断的多发性骨髓瘤患者中的总体缓解率达到了83%，且缓解效果随时间推移而加深。今年晚些时候，我们将在一次医学会议上报告最新结果。总体而言，这些数据让我们有信心在骨髓瘤的早线和前体细胞治疗中，将Lynozyfic作为单一疗法或简化联合疗法来使用。 ThoughIwon'tgointodetailonodronextamabtoday,IwanttohighlightthatourPhase3studyevaluatingodronextamabasfirst-linemonotherapy against the standard of care in follicular lymphoma patients is fully enrolled. Similarly to Lynozyfic, odronextamab demonstratedpotentiallybest-in-class efficacy in late-line patients, driving our enthusiasm for this approach in the earlier line settings. 虽然我今天不会详细介绍odronextamab，但我想强调的是，我们评估odronextamab作为滤泡性淋巴瘤患者一线单药治疗与标准治疗相比的III期研究已完成入组。与Lynozyfic类似，odronextamab在晚线患者中表现出潜在的同类最佳疗效，这激发了我们在早期治疗情景中对这种方法的热情。 I'dalsoliketoremindyouthatinthelead-incohortforthisPhase3studyinfirstlinefollicularlymphoma,odronextamabmonotherapydemonstrateda100%completeresponserate,furtherreinforcingthepotentialofodronextamabinthissetting. 我也想提醒大家，在这项针对初治滤泡性淋巴瘤的III期研究的导入队列中，odronextamab单药治疗表现出100%的完全缓解率，进一步证明了odronextamab在这一治疗场景中的潜力。 MovingontoourC5andcomplementinhibitorprograms.LetmeremindyouthatinparoxysmalnocturnalhemoglobinuriaorPNH,wheredeep blockade of C5 seems critical to prevent breakthroughhemolysis and potentially catastrophic events, the lead-in cohort for our Phase 3 study demonstrated there are once-monthly subcutaneous regimen, combining a C5 antibody with a C5 siRNA, may provide the best-in-class disease controlwiththebest-in-classconvenience. 接下来谈谈我们的C5和补体抑制剂项目。我想提醒大家，在阵发性睡眠性血红蛋白尿症（PNH）中，深度阻断C5似乎对于防止突破性溶血和潜在的灾难性事件至关重要。我们III期研究的导入队列表明，每月一次的皮下给药方案，将C5抗体与C5 siRNA相结合，可能提供同类最佳的药物控制效果和便利性。 For PNH patients, we have also just initiated our first-in-human study of our siRNA targeting Complement Factor B, primarily intended for the 20% to30%ofpatientswhoremainanemicdespiteoptimalC5therapyduetoso-calledextravascularhemolysis. 对于阵发性夜间血红蛋白尿症（PNH）患者，我们还刚刚启动了针对补体因子B的siRNA首次人体研究，该研究主要针对20%至30%的患者，这些患者由于所谓的血管外溶血，在接受最佳C5治疗后仍持续贫血。 MovingontoourC5programingeneralizedmyastheniagravis.Inthethirdquarter,weannouncedpositive Phase 3resultsforourC5siRNA,cemdisiran.This siRNA conveniently dosed subcutaneously every three months,showed statistically significant results for the primary endpoint, improvementintheMG-ADLscorecomparedtoplacebo,andnumericallybetterresultscomparedtootherC5inhibitortherapiesincross-trialcomparisons. 接下来谈谈我们针对全身性重症肌无力的C5项目。在第三季度，我们宣布了C5 siRNA药物cemdisiran的III期试验积极结果。该siRNA药物每三个月皮下注射一次，与安慰剂相比，在主要终点指标（即MG-ADL评分改善）上表现出统计学显著性，并且在临床试验横向对比中，其结果在数值上优于其他C5抑制剂疗法。 The convenience advantage for patients currently being treated with regular intravenous infusions, together with its efficacy and safety profile, positions cemdisiran as apotential best-in-class treatment optionfor this debilitating neuromusculardisorder. Weare planning onsubmitting a USregulatoryapplicationforcemdisiranmonotherapyinthefirstquarterof2026,pendingFDAdiscussions,withglobalsubmissionstofollow. 对于目前接受常规静脉注射治疗的患者而言，cemdisiran的便利性优势，加上其疗效和安全性，使其成为这种使人衰弱的神经肌肉疾病的潜在最佳治疗选择。我们计划在与FDA讨论后，在2026年第一季度向美国食品药品监督管理局（FDA）提交cemdisiran单药治疗的监管申请，然后向全球其他地区提交申请。 Finally, for ourC5program, in termsof ourefforts in ophthalmology, we are hopingtocompleteenrollmentin the first quarter of 2026for the lead-incohortofourfirstPhase3studyingeographicatrophy,withinitialresultsexpectedbytheendof2026. 最后，关于我们的C5项目，在眼科领域方面，我们希望在2026年第一季度完成我们首个针对地理性萎缩的III期研究的导入队列的入组工作，预计2026年底可获得初步结果。 Additionally in ophthalmology, I'd like to note that we are initiating a clinical trial in active non-infectious uveitis of an intravitreally-delivered CD3 monoclonalantibodywhichisdesignedtolocallyblockautoimmuneTcellactivityintheeye,markingthefirstinanewseriesofnovelophthalmologytargetsthatwewillbeprogressingtotheclinicoverthenextyear. 此外，在眼科领域，我想指出的是，我们正在启动一项针对活动性非感染性葡萄膜炎的临床试验，该试验使用玻璃体内注射的CD3单克隆抗体，旨在局部阻断眼内的自身免疫性T细胞活性，这标志着我们将在未来一年内推进至临床的一系列新型眼科靶点中的首个。 Turningtoouranticoagulationeffortsandinparticular,toourFactorXIprograminvolvingtwodifferentantibodiesdesignedtotailoranticoagulation therapy for each individual patient'sneeds.Pivotalstudies in post-operativevenousthromboembolismfollowing totalknee replacementsurgeryareinprogresswithdataanticipatedin2027.Pivotalstudiesinotheranticoagulationindicationsaresettolaunchinthecomingmonths. 接下来谈谈我们的抗凝治疗工作，特别是我们的因子XI项目，该项目涉及两种不同的抗体，旨在为每位患者量身定制抗凝治疗方案。全膝关节置换术后静脉血栓栓塞的关键研究正在进行中，预计2027年将得出数据。其他抗凝治疗适应症的关键研究将在未来几个月内启动。 OnNovember10,wewillkickoffanewinvestoreventseriescalled, TheRegeneron Roundtable, whichwillspotlightourvariousinnovativepipeline programs, starting with our Factor XI story in which we will provide, for the first time, exciting new clinical data in trials exploring the Factor XI antibodiesincatheter-associatedthrombosisandaprovokedsubclinicalGIbleedingstudy. 11月10日，我们将启动一项名为“再生元圆桌会议”的新投资者活动系列，该系列将聚焦于我们的各项创新在研项目，首先将介绍我们的因子XI故事，我们将首次提供令人振奋的新临床数据，这些数据来自探索因子XI抗体在导管相关性血栓形成中的作用的试验，以及一项激发性亚临床胃肠道出血的研究。 UpcomingRegeneronRoundtableswill spotlight our opportunities in hematologic andsolidtumor oncology, obesity, andotherareas. 即将举行的Regeneron圆桌会议将聚焦我们在血液肿瘤、实体肿瘤、肥胖症以及其他领域的机会。 Moving to our growing siRNA portfolio, coming out of our research collaboration with Alnylam. I'd like to highlight our ongoing clinical studies, including our PNPLA3 andCIDEB siRNAs in NASH; our SOD andHTTsiRNAs in amyotrophic lateralsclerosis and Huntington's disease;andin addition, weplantobeginclinicaltrialsforalpha-synucleinsiRNAforParkinson'sdiseaseandourMAP-tausiRNAforAlzheimer'sinthecomingmonths. 接下来，我想介绍我们日益丰富的siRNA产品组合，这是我们与Alnylam公司研究合作的成果。我想重点介绍我们正在进行的临床研究，包括针对非酒精性脂肪性肝炎（NASH）的PNPLA3和CIDEB siRNAs；针对肌萎缩侧索硬化症和亨廷顿舞蹈症的SOD和HTT siRNAs；此外，我们计划在未来几个月内开始针对帕金森病的α-突触核蛋白siRNA和针对阿尔茨海默病的微管相关蛋白tau siRNA的临床试验。 Finally, I'd like to highlight our commitment to developing innovative new approaches in the ultra-rare disease space. In the third quarter, we announcedunprecedentedclinicalbenefitusinggaretosmabinourPhase3OPTIMAtrialinfibrodysplasiaossificansprogressivaorFOP.Individuals sufferingfromthistragicgeneticdisorderprogressivelyreplacetheirmuscleandsofttissuewithabnormalboneformation,encasingthemselvesinahorrificosseouscage. 最后，我想强调我们在超罕见疾病领域开发创新方法的承诺。在第三季度，我们宣布，在我们的III期OPTIMA试验中，使用加雷妥珠单抗（garetosmab）治疗纤维发育不良性进行性骨化症（FOP）取得了前所未有的临床益处。患有这种悲剧性遗传疾病的患者，其肌肉和软组织会逐渐被异常骨组织所替代，将自己包裹在一个可怕的骨笼中。 Remarkably, in the OPTIMA trial, we're able to demonstrate a greater than 99% reduction in abnormal bone formation at 56 weeks, offering great hopeforthisultra-raregeneticdisorder.RegeneronplansaUSregulatorysubmissionbytheendof2025. 令人瞩目的是，在OPTIMA试验中，我们能够证明在56周时异常骨形成减少了99%以上，这为这种极为罕见的遗传性疾病带来了巨大的希望。Regeneron计划在2025年底前向美国监管机构提交上市申请。 We arealsoprovidingnewhope forchildrensufferingfromanotherultra-raregeneticdisorderinwhichabsence oftheOTOFgeneresultsin profoundgenetichearing loss.As we recently describedin theNewEnglandJournal ofMedicine, our novel gene therapyapproach provided meaningfulhearinggainsin11outof12treatedchildren,withseveralachievingnormalhearinglevels. 我们还为患有另一种超罕见遗传性疾病的儿童带来了新的希望，这种疾病由于OTOF基因的缺失会导致严重的遗传性听力损失。正如我们最近在《新英格兰医学杂志》上所述，我们创新的基因治疗方法使12名接受治疗的儿童中有11名听力得到了显著提升，其中几名甚至达到了正常听力水平。 The FDA recently announced that this program was the first new molecular entity selected for a Commissioner's National Priority Voucher, and we are finalizing preparations for a US regulatory submission this year. This program highlights Regeneron's commitmentto advancing the leading edge of biotechnology. 美国食品药品监督管理局（FDA）最近宣布，该计划是首个入选委员国家优先券的新分子实体，我们正在为今年向美国监管机构提交申请做最后的准备。该计划彰显了再生元公司致力于推动生物技术前沿发展的决心。 In summary, Regeneron has delivered a quarter filled with positive clinical readouts, advancingour pipeline and reinforcing our leadership and scientificinnovation,fromgroundbreakingadvancesaddressingsomeofthemostcommonmedicalconditions,totransformativeinnovationin theultra-rarediseasespace. 总之，Regeneron公司本季度取得了众多积极的临床结果，推动了我们的产品线发展，并巩固了我们的领导地位和科学创新能力，从针对一些最常见疾病的突破性进展，到超罕见疾病领域的变革性创新。 Withthat,letmeturnitovertoMarion. 说到这里，我就把时间交给Marion。 MarionMcCourt-ExecutiveVicePresident-Commercial 玛丽昂·麦考特 - 商业执行副总裁 Thanks, George.Ourthird quarter performance highlights thestrength of Regeneron's commercialportfolio. Today's results demonstrate ourabilitytodrive growth ofinlinebrandsandtoaccelerate launch opportunities, deliveringour transformative medicines toevenmore patients. 谢谢，乔治。我们第三季度的业绩彰显了Regeneron商业组合的强劲实力。今天的业绩表明，我们有能力推动自有品牌的发展，加速产品上市，让更多患者用上我们的变革性药物。 BeginningwithEYLEAHDandEYLEA,totalcombinedthirdquarterUSnetsaleswere$1.11billion,comparableonasequentialbasis.Asthedecrease inEYLEAnetsaleswasoffsetbyanincreaseinEYLEAHDnetsales,EYLEAHDnetsalesgrew10%quarteroverquarterto$431million,againgrowing fasterthananyotherinnovativemedicineinthecategory. 以EYLEA HD和EYLEA为起点，第三季度美国总净销售额为11.1亿美元，与上一季度相比基本持平。由于EYLEA净销售额的下降被EYLEA HD净销售额的增加所抵消，EYLEA HD净销售额环比增长10%，达到4.31亿美元，增速再次超过该类别中的任何其他创新药物。 EYLEA HD unit demand grew18% quarteroverquarter whichwas partially offset by ongoing competitive pricing pressureswithinthe category. AsEYLEAHDgrew,EYLEA's third quarter USnetsalesdecreased 10% quarteroverquarter to $681 million reflecting acommensuratedecline in unit demand driven by the ongoing conversion to EYLEA HD, patient affordability issues, and competitive dynamics. We expect a similar demand declineinthefourthquarterforEYLEA,alongwithongoingpricingpressure. EYLEA HD的需求量环比增长18%，但这一增长部分被该品类内部持续的竞争性定价压力所抵消。随着EYLEA HD的增长，EYLEA第三季度在美国的净销售额环比下降10%，至6.81亿美元，这反映了由于持续向EYLEA HD的转换、患者负担能力问题以及竞争动态，单位需求量相应下降。我们预计，在持续的定价压力下，EYLEA第四季度的需求量也将出现类似下降。 Together,EYLEA HDandEYLEAleadthe branded anti-VEGFcategorybasedonbest-in-classefficacy,safety, andwithEYLEA HDdurability.And EYLEAHDnowrepresentsapproximately40%ofRegeneron'sUSretinafranchise. 凭借同类最佳的疗效、安全性以及EYLEA HD的持久性，EYLEA HD和EYLEA共同引领着抗血管内皮生长因子（VEGF）类创新药。目前，EYLEA HD约占再生元美国眼科业务的40%份额。 Lookingaheadtothefourth quarterforEYLEAHD,weanticipatesequentialdemand growthtomoderatetohighsingle-digitsasweawaitlabel enhancements.Once approved,we believe theseenhancementshave the potential togenerate asignificant positive inflectionindemand. 展望Eylea HD的第四季度，我们预计需求环比增长将放缓至中高个位数，同时我们也在等待标签的改进。一旦获得批准，我们相信这些标签改进有望显著提振需求。 NowtoDupixent. Thirdquarterworldwidenetsales reached$4.9billion,growing 26%on aconstant currencybasiscomparedtotheprior year. IntheUS,Dupixent'snetsalesreached$3.6billionreflecting28%year-over-yeargrowth.Dupixentleadsthemarketacrossallestablishedindications including atopic dermatitis, asthma, nasal polyps, andeosinophilic esophagitis. In addition, Dupixent is the main beneficiary of competitor marketgrowtheffortsbasedonitsprovenefficacy,safety,easeofaccess,andabilitytoaddressunmetpatientneeds. 接下来是Dupixent。第三季度全球净销售额达到49亿美元，按固定汇率计算，同比增长26%。在美国，Dupixent的净销售额达到36亿美元，同比增长28%。Dupixent在所有已确立的适应症（包括特应性皮炎、哮喘、鼻息肉和嗜酸性食管炎）中均占据市场领先地位。此外，凭借其经过验证的疗效、安全性、易获取性以及满足患者未满足需求的能力，Dupixent是竞争对手市场拓展努力的主要受益者。 Our recent launches in COPD, chronic spontaneous urticaria, and bullous pemphigoid are progressing very well. Across all launches, Dupixent's differentiated clinical profile and growing physician experience are driving strong uptake. InCOPD, prescribers see Dupixent's benefits across a rangeofappropriatepatienttypes,andrecentmarketresearchfoundpulmonologistsexpectedtosubstantiallyincreasetheirprescribingof Dupixentoverthenext12months. 我们最近在慢性阻塞性肺疾病（COPD）、慢性自发性荨麻疹和大疱性类天疱疮领域的商业化进展非常顺利。在所有新适应症商业化努力中，度普利尤单抗独特的临床特征和不断增长的医生经验正在推动其强劲增长。在COPD领域，处方医生看到度普利尤单抗在一系列合适的患者类型中均显示出益处，最近的市场调查发现，肺科医生预计在未来12个月内将大幅增加度普利尤单抗的处方量。 [Additionally],therehasbeenrapiduptakeamongchronicspontaneousurticariapatientsasbothdermatologistsandallergistsembraceDupixent.Inbullouspemphigoid, Dupixentisthe firstbiologicmedicineaddressing acriticalunmetneed. Physiciansareeagerto transition elderly patients off steroid therapy, with Dupixent offering them a safer and more effective alternative. [此外]，随着皮肤科医生和过敏科医生对度普利尤单抗的广泛采用，慢性自发性荨麻疹患者对该药物的使用率迅速提升。在大疱性类天疱疮治疗方面，度普利尤单抗是首个满足关键未满足需求的生物药物。医生们迫切希望帮助老年患者停用类固醇治疗，而度普利尤单抗为他们提供了一种更安全、更有效的替代方案。 In summary, Dupixent continues to transform the lives of patients across indications, geographies, and age groups from as young as 6 months. Therearecurrentlymorethan1.3 millionpatientsworldwidebenefitingfromDupixentformultipleType2diseases. 总之，度普利尤特（Dupixent）继续在各种适应症、各地区以及包括低至6个月的各年龄组的群体中改变患者的生活。目前，全球有超过130万名患者因多种2型疾病而受益于度普利尤特。 Turning to oncology and hematology, in the third quarter, Libtayodelivered $365 million worldwide net sales, growing 24% on a constant currency basiscomparedwiththeprioryear.IntheUS,Libtayonetsalesgrew12%yearoveryearto$219millionbasedonstrongdemandacrossallapproved indications. 在肿瘤学和血液学领域，第三季度，Libtayo的全球净销售额达到3.65亿美元，按固定汇率计算，同比增长24%。在美国，由于所有获批适应症的需求强劲，Libtayo的净销售额同比增长12%，达到2.19亿美元。 Innon-melanomaskincancers,Libtayo'sstrongperformanceisbasedonestablishedmarketleadershipandongoingcategorygrowth.Wearemakingencouraging early progress with US launch in adjuvant CSCC where physicians are already embracing Libtayo as a new treatment option. We estimatethatupto10,000eligiblepatientsmaybenefitfromLibtayointhissetting. 在非黑色素瘤皮肤癌领域，Libtayos的强劲表现得益于其稳固的市场领导地位和持续的细分市场增长。我们在美国推出的辅助治疗CSCC（基底细胞癌）方面取得了令人鼓舞的早期进展，医生们已经将Libtayo视为一种新的治疗选择。我们估计，在这种情况下，多达10,000名符合条件的患者可能从Libtayo中受益。 Andnow,inlungcancer,Libtayoisnowthesecondmostcommonlyprescribedimmunotherapyfornewlydiagnosedpatients.PhysiciansincreasinglyrecognizeLibtayoasanimportanttreatmentoptionbasedonclinicalexperience,versatilityasamonotherapyorincombinationwithchemotherapy, andanincreasingbodyofclinicalevidenceincludingrecentfive-yearsurvivaldata. 目前，在肺癌治疗中，Libtayo已成为新诊断患者第二大最常用的免疫疗法。基于临床经验、作为单一疗法或与化疗联合使用的多适用性，以及包括最新五年生存数据在内的日益增多的临床证据，医生们越来越认识到Libtayo是一种重要的治疗选择。 OutsidetheUS,Libtayosalesreached$146million,growing47%yearoveryearonaconstantcurrencybasis,supportedbysustaineddemandand ongoinglaunchesininternationalmarkets. 在美国以外地区，Libtayo的销售额达到1.46亿美元，按固定汇率计算同比增长47%，这得益于国际市场的持续需求和不断推出的新适应症上市。 Movingto our new hematology therapy, Lynozyfic, we've made strong early progress in commercializing this importantbispecific for fifth line multiplemyelomapatients.Positivelaunchindicatorsincludephysicianfeedback,formularylistings,pathwayinclusions,completionofREMsrequirements, and payer coverage. While we expect modest revenue contribution in this heavily pre-treatedpopulation, Lynozyfic is an important therapeutic advance tothehematologycommunity, andwe lookforwardtoadditionalclinical datasupportingitspotentialuseinearliertreatment settings. 接下来谈谈我们的新型血液疗法Lynozyfic，我们在这个重要双抗多发性骨髓瘤五线患者商业化方面取得了早期显著进展。积极的上市指标包括医生反馈、处方集列表、纳入医保目录、完成风险评估与缓解策略要求（REMs）、支付方覆盖。虽然我们预计在这个经过大量预处理的人群中，Lynozyfic的收入贡献将较为有限，但它在血液学界是一项重要的治疗进展，我们期待更多的临床数据来支持其在早期治疗环境中的潜在应用。 Insummary,inthethirdquarter,RegenerondeliveredongoinggrowthacrossEYLEAHD,Dupixent,andLibtayo,andmadeimportantprogressin several launches. Our commercial portfolio is well-positionedto capitalize on manynear-term growth opportunities, enabling us to deliver more treatmentstomorepatients. 综上所述，在第三季度，Regeneron公司在Eylea HD、Dupixent和Libtayo方面实现了持续增长，并在多项产品上市方面取得了重要进展。我们的商业组合处境良好，可以抓住众多近期增长机遇，使我们能为更多患者提供更多治疗选择。 Withthat,I'llturnthecalltoChris. 说完这些，我将把电话转给克里斯。 ChristopherFenimore-ChiefFinancialOfficer,ExecutiveVicePresident-Finance 克里斯托弗·费尼莫尔 - 首席财务官、财务执行副总裁 Thankyou,Marion.MycommentstodayonRegeneron'sfinancialresultsandoutlookwillbeonanon-GAAPbasisunlessotherwisenoted. 谢谢你，Marion。除非另有说明，否则我今天对Regeneron财务业绩和前景的评论将以非美国通用会计准则（GAAP）为基础。 Third-quarter 2025 total revenues of $3.8 billion grew 1% compared to the prioryear, reflecting higher Sanofi collaboration revenue driven by strongDupixentsalesgrowthandcontinuedgrowthinnetsalesofLibtayogloballyandEYLEAHDintheUS,partiallyoffsetbylowernetsalesof EYLEAintheUSandlowerBayercollaborationrevenue.Third quarterdilutednetincomepersharewas$11.83onnetincomeof$1.3billion. 2025年第三季度，公司总收入为38亿美元，同比增长1%，这主要得益于强劲的Dupixent销售增长以及Libtayo在全球和EYLEA HD在美国的净销售额持续增长，从而带来了更高的赛诺菲合作收入，但部分被EYLEA在美国的净销售额下降和拜耳合作收入减少所抵消。第三季度，公司净收入为13亿美元，每股摊薄净收益为11.83美元。 BeginningwiththeSanoficollaboration,revenueswereapproximately$1.6billion,ofwhich,$1.5billionrelatedtoourshareofcollaborationprofits. Regeneron'sshareofprofitsgrew34%versustheprioryeardrivenbyvolumegrowthforDupixentandimprovingcollaborationmargins. 从与赛诺菲的合作开始谈，合作收入约为16亿美元，其中15亿美元与我们应得的合作利润份额相关。得益于度普利尤单抗的销量增长和合作利润率的提升，再生元应得的利润分成较上年增长了34%。 The Sanofi development balance was approximately $900 million at the end of the third quarter, reflecting a reduction of approximately $300 million sincethe end ofthe secondquarter andapproximately$730 million sincethestartof the year.Dupixent's continued strengthhas enabledarapidreimbursementofthedevelopmentbalancein2025. And we nowexpect thisbalance tobe fullyreimbursedbynolaterthanthe endof thethirdquarterof2026. 截至第三季度末，赛诺菲的开发余额约为9亿美元，自第二季度末以来减少了约3亿美元，自年初以来减少了约7.3亿美元。度普利尤单抗的持续强劲表现使得开发余额在2025年得以快速偿还。我们现在预计，这一余额最迟将于2026年第三季度末前全额偿还。 MovingtoBayer.ThirdquarternetsalesofEYLEAandEYLEA8mgoutsidetheUSwere$854million,inclusiveof$232millionofEYLEA8mgsales. TotalBayercollaborationrevenuewas $345million,ofwhich,$312millionrelatedtoourshareofnetprofitsoutsidetheUS. 转至拜耳公司。第三季度，美国以外的EYLEA和EYLEA 8 mg净销售额为8.54亿美元，其中包括EYLEA 8 mg的销售额2.32亿美元。拜耳合作总收入为3.45亿美元，其中3.12亿美元与我们应占的美国以外净利润份额相关。 Other revenue in the third quarter was $198 million which included $165 million of profit share and royalties associated withlicense agreements. TheincreasefromtheprioryearwasdrivenbyhigherroyaltyincomefromIlarisandgrowthinourshareofprofitsfromArcalyst. 第三季度其他收入为1.98亿美元，其中包括1.65亿美元的利润分成以及与许可协议相关的特许权使用费。与上一年相比有所增长，主要得益于Ilaris特许权使用费的增加以及Arcalyst利润分成的增长。 Nowto our operating expenses. R&D expense was $1.3billionin the third quarter,reflecting continuedinvestments tosupport Regeneron's innovativelate-stagepipeline,includingourpivotalprogramsforLynozyficandOrdsponoinearlierlinesofmyelomaandlymphoma,ourFactor XIprograminanticoagulationindications,andourongoingeffortsinotherclinicalprograms. 接下来是我们的运营费用。第三季度研发费用为13亿美元，这反映了我们持续投资以支持Regeneron创新的后期研发管线，包括我们针对骨髓瘤和淋巴瘤早线治疗的关键项目Lynozyfic和Ordspono、抗凝适应症中的XI因子项目，以及我们在其他临床项目中持续的努力。 Thirdquarter SG&Awas $541million down 12%fromtheprior year, primarilydrivenbylowercharitablecontributions toanindependent non-profit patient assistance foundation. Third quarter 2025gross margin on net product sales was 86%.The lower gross margin versus the prior year reflectsachangingproductmixandhigherongoinginvestmentstosupportourmanufacturingoperations. 第三季度销售、一般及管理费用（SG&A）为5.41亿美元，同比下降12%，主要原因是向一家独立的非营利性患者援助基金会的慈善捐款减少。2025年第三季度净产品销售的毛利率为86%。毛利率较去年同期有所下降，反映了产品组合的变化以及为支持我们的制造业务而持续增加的投资。 Regenerongenerated$3.2billioninfreecashflowthroughthefirstninemonthsof2025andendedthequarterwithcashandmarketablesecurities, less debt, of approximately $16 billion. Through the first nine months of 2025, we have repurchased approximately $2.8 billion of our shares, the most ever allocated to open market repurchases in any full fiscal year in our history. We continue to be opportunisticbuyers of our shares and anticipatereturningapproximately$4billiontoshareholdersthroughdividendsandrepurchasesin2025. 2025年前九个月，Regeneron公司产生了32亿美元的自由现金流，截至本季度末，公司的现金和有价证券（扣除债务）约为160亿美元。2025年前九个月，我们回购了约28亿美元的股票，这是我们历史上任何一个完整财年公开市场回购金额最多的一次。我们继续作为我们股票的机会型买家，并预计在2025年通过分红和回购向股东返还约40亿美元。 Movingtoguidancefor2025.Wehaveupdatedandnarrowedtherangesacrossourfinancialguidancewhichcanbefoundinourpressrelease issuedearlierthismorning.Finally,asweturnto2026,wecontinuetomakesignificantprogressacrossourinnovativepipelineandanticipateadvancingmultiplelargeregistrationalprogramsinmyeloma,lymphoma,anticoagulation,obesity,andotherhematologyandsolidtumoroncologyprograms,aswellasseveralnewassetsintotheclinic. 接下来是2025年的业绩预期。我们已更新并缩小了财务预期的范围，相关内容见我们今天上午早些时候发布的新闻稿。最后，展望2026年，我们的创新药物研发管线继续取得重大进展，预计将在骨髓瘤、淋巴瘤、抗凝、肥胖症以及其他血液学和实体肿瘤学项目中推进多个大型注册研究项目，同时还将有数个新药进入临床阶段。 Webelieveinvestingintheseprogramscandrivesignificantlong-termvalue.Andtosupporttheseefforts,wecurrentlyexpectamid-teenspercentageincreaseinR&Dexpensein2026relativeto2025.Wewillprovidedetails on2026guidanceforotherlineitemsearlynextyear. 我们认为，投资这些项目能够带来显著的长期价值。为了支持这些努力，我们目前预计2026年的研发费用将比2025年增长中双位百分数左右。明年年初，我们将提供2026年其他利润表项目的详细指引信息。 Inconclusion,Regeneron'sthirdquarterresultsdemonstratetheongoingstrengthofourbusinessandenableustocontinueinvestinginour differentiated pipeline to deliversignificant advances forpatientsand drive long-term value for shareholders. 总之，Regeneron第三季度的业绩表明我们的业务持续强劲，使我们能够继续投资于我们的差异化产品线，为患者带来重大进步，并为股东创造长期价值。 Withthat,I'llpassthecallbacktoRyan. 说完，我会把电话转给瑞安。 RyanCrowe-SeniorVicePresident-InvestorRelations Ryan Crowe - 投资者关系高级副总裁 Thank you, Chris. This concludes our prepared remarks. We will nowopen thecall for Q&A. To ensure we are able to address as many questions as possible,wewillansweronequestionfromeachcallerbeforemovingtothenext.Shannon,canwepleasegotothefirstquestion,please? 谢谢，克里斯。我们的准备发言到此结束。现在开始问答环节。为了确保我们能够尽可能多地回答问题，我们将先回答每位提问者一个问题，然后再进行下一个问题。香农，请开始第一个问题，好吗？ QUESTIONSANDANSWERS 问题与回复 AkashTewari-Jefferies-Analyst 阿卡什·特瓦里 - 杰富瑞 - 分析师 Hey.Thankssomuch.ItseemslikeyourteamhasretooledyourcommercialstrategyonEYLEAanditseemsrelatedtokindofprice.Whatareyou doingonagroundlevelwhenitcomestovolume-baseddiscounts that’sallowingyoutotakeshare fromRocheandAmgen?Andareyouseeing morepriceerosiononEYLEA?Arewealsoseeingthatdiscountingonhighdose?Andmaybejustlastly,shouldwecontinuetoseevolumegains andrevenuegainsaheadofthelabelenhancement potentiallymidyear?Thankssomuch. 嘿。非常感谢。看起来你们的团队已经对EYLEA的商业策略进行了调整，而且似乎与价格有关。在基于销量的折扣方面，你们具体做了哪些工作，从而能够从罗氏和安进手中夺取市场份额？你们是否发现EYLEA的价格正在进一步下降？我们是否也看到高剂量产品的折扣？最后，在标签改进可能于年中实施之前，我们的销量和收入是否会继续增长？非常感谢。 LeonardSchleifer-Co-ChairmanoftheBoard,President,ChiefExecutiveOfficer,Co-Founder 伦纳德·施莱弗 - 董事会联席主席、总裁、首席执行官、联合创始人 Well, I think youmay have set the record for the number of questions we're not going to answer. Not because we don't want to, Marion would love to,butIthinkthatthere'ssomanycompetitiveissuesongoingthereintermsofourstrategyontheground,ourrebates,andsoforth.SoI'mnot surewe'reabletoreallyhelpyououtthere.Marion,I don'tknowifyouwanttoaddanything? 嗯，我觉得你可能创下了我们不回答问题数量的纪录。不是因为我们不想回答，玛丽恩（Marion）也很想回答，但我认为，就我们在实地的策略、返利等方面而言，目前存在太多竞争问题。所以我不确定我们是否真的能帮到你。玛丽恩，你还有什么想补充的吗？ MarionMcCourt-ExecutiveVicePresident-Commercial 玛丽昂·麦考特 - 执行副总裁-商业 Well,IthinkIwouldjustaddthatwhenwelookattheEYLEAHDperformanceinthequarter,the[favorability]thatwe'reseeingcertainly is related to EYLEA HD, the product and the science. And retina specialists see the clinical efficacy, the safety, and now durability with EYLEAHDandthatismakingabigdifference. 嗯，我想补充一点，当我们审视本季度EYLEA HD的表现时，我们所看到的[正面评价]当然与EYLEA HD这款产品及其科学原理有关。视网膜专家看到了EYLEA HD的临床疗效、安全性以及现在的持久性，这产生了很大的影响。 Leonard Schleifer -Co-Chairman of the Board, President, ChiefExecutive Officer, Co-Founder  Wedoseethatuntilwegettheseenhancementsinplace,wecan't,Ithink,seeasignificantupswing. 伦纳德·施莱弗- 董事会联席主席、总裁、首席执行官、联合创始人 我们的确认为，在我们实现这些改进之前，我认为我们不会看到显著的上升。 MarionMcCourt-ExecutiveVicePresident-Commercial 玛丽昂·麦考特  - 商业执行副总裁 Len, if you like, I can highlight what I shared a moment ago, but just to answer thequestion a bit more completely, for EYLEA HD, I mentioned we anticipatetosequentialdemandgrowthtomoderatetohighsingle-digitsasweawaitlabelenhancements.Andwealsomadeacommenton EYLEAthatweanticipatesimilarlevelsofdemandreductioninthecomingquarter.AndasInotedtoday,wesawa10%reductioninEYLEA2 milligrams,andthatwasintermsofthelowerdemandquarteroverquarter.Ihopethat'shelpful. Len，如果你愿意，我可以强调一下我刚才分享的内容，但为了更全面地回答这个问题，关于EYLEA HD，我提到过，在我们等待标签改进期间，我们预计需求将逐步增长至中高个位数。同时，我们也对EYLEA发表了评论，预计下一季度需求将出现类似幅度的下降。正如我今天提到的，EYLEA 2毫克的需求环比下降了10%。希望这能帮到你。 Ryan Crowe - Senior Vice President-Investor Relations Okay. Thanks, Len and Marion. Let's move to the next question, please, Shannon. 瑞安·克罗  - 投资者关系高级副总裁 好的。谢谢，莱恩和玛丽昂。香农，请继续下一个问题。 GeoffreyMeacham-Citi-Analyst 杰弗里·米查姆 - 花旗银行 - 分析师 Morning,guys.Thanksforthequestion.IguessforChrisorLen,onutilizingthebalancesheet,youguyshaven'thistoricallydonelargerscaleBD and it seems like that's going to be the casegoing forward. But in manufacturing,what's the appetiteto further expand your plans that you've announced just so you own all elements of manufacturing? Obviously, that would be viewed pretty favorably by the Trump administration as well. Thankyou. 早上好，各位。谢谢提问。我想针对克里斯或莱恩，关于资产负债表的运用，你们公司历史上似乎没有进行过大规模的业务开发（BD），而且看起来未来也不会这么做。但在制造业方面，你们是否有意愿进一步扩大已公布的计划，以便掌控制造业的所有要素？显然，特朗普政府也会对此持相当积极的看法。非常感谢。 LeonardSchleifer-Co-ChairmanoftheBoard,President,ChiefExecutiveOfficer,Co-Founder 伦纳德·施莱弗 Yeah. Great question, Geoff. Just on whether or not we would use our balance sheet for large deals, we certainly have no allergy to doing that, if we saw the right opportunity. So it's not a question of philosophy there. It's really a question of what would make sense where we think we could createadditionalvalue. 是啊。杰夫，这个问题问得很好。关于我们是否会利用资产负债表进行大型交易，如果我们看到了合适的机会，我们当然不会对此有所顾虑。所以，这并不是一个涉及理念的问题。真正的问题是，在我们认为能够创造额外价值的地方，什么才是合理的做法。 In terms of investing further in manufacturing, and as I said during our [remarks], we've been talking about the need for domestic manufacturing since2014,Ithink,intestimonybeforeCongress.Wementionedtheover$7billioninvestmentplan. 关于进一步投资制造业，正如我在我们的讲稿中所说，我认为，自2014年以来，在国会作证时，我们就一直在谈论国内制造业的必要性。我们提到了超过70亿美元的投资计划。 But I think you do highlight onepiece of the whole puzzle that we do not have adequate positioning in is the filling. But I'm pleased to say that we would expect our filling plant tocome, which we'veinvested quite a bit in, Geoff, it'snow ready to go, and we expect it to come online during the comingyear.Sothat'sagreatquestion,anditshouldhelpussortofcontrolallaspectsofthestandardbiologicsmanufacturing. 但我认为你确实指出了整个难题中的一个关键点，那就是我们在灌装环节的布局不足。不过，我很高兴地告诉大家，我们投资的灌装工厂即将投入使用，Geoff，它现在已经准备就绪，预计将在明年上线。这个问题问得很好，它有助于我们全面掌控标准化生物制剂的生产。 ChrisRaymond-RaymondJames-Analyst 克里斯·雷蒙德 - 雷蒙德·詹姆斯 - 分析师 Thanksfortakingthequestion. It'smaybe aquestiononEYLEAHD,Marion, IthinkI'veheardyoutalkalotaboutthe importance ofthelabeling enhancementsand Len, I just heard your commentabout share and how important they are.But I think we'vecome to understand maybe theprimary need here and the reason for these enhancements and why they're important is for certain clinics to have dosing flexibility so they can center their inventory around one drug. But just maybe, Marion, as you've seen this market evolve, can you talk about how that clinic inventory policies have evolved over time and especially how private equity in the space may be influencing this? Or is this really more of as you're looking for share with clinics that don't necessarily have relatively aggressive inventory policies. 感谢你接收这个问题。这可能是关于艾力雅高剂量版（EYLEA HD）的问题，玛丽昂，我想我听过你多次谈及标签更新的重要性；Len，我刚听到你关于市场份额及其重要性的看法。不过我们逐渐理解到，或许此次标签更新的核心需求和重要性所在，是为了让部分诊所获得给药灵活性，从而能将库存集中在一款药物上。但玛丽昂，随着你见证这个市场的发展，能否谈谈诊所的库存政策是如何演变的？尤其是该领域的私募股权可能对此产生了怎样的影响？或者说，这是否更多是为了争取那些库存政策并不太激进的诊所的市场份额？ MarionMcCourt-ExecutiveVicePresident-Commercial 玛丽昂·麦考特 - 商业执行副总裁 Thanks. SoChris,mycomment willbethattheretinacommunityandcertainly,retinaKOLs,look for the ability toselect therightproduct fortheir patients. And I'm not an expert in inventory, but I can share with you that EYLEA HD is a newer branded product in the category two years in the market now, certainly, availability, not only inventory-wise, but payer coverage-wise. 谢谢。克里斯，我的观点是，视网膜疾病领域，当然还有视网膜疾病的关键意见领袖（KOL），都在寻求能为患者选择合适产品的能力。我并不是库存方面的专家，但我可以告诉你，艾力雅高剂量版（EYLEA HD）是该领域较新的一款品牌药，目前已上市两年。当然，其可及性不仅体现在库存层面，也体现在支付方承保范围上。 And then as Imentioned a moment ago, the most important characteristics ofthe product is this element ofprofound clinical efficacy, safety that peoplereallycancounton.Andthen,ofcourse, withEYLEAHD,they'regetting,forappropriatepatients,theabilitytohavedurabilitythatisvery,veryimportantforthepatientsandtheircaretakers. 正如我刚才提到的，该产品最重要的特点在于其具有显著的临床疗效和安全性，这是患者可以信赖的。当然，对于合适的患者而言，EYLEA HD能够提供持久疗效，这对于患者及其护理人员来说至关重要。 Ryan Crowe - Senior Vice President-Investor Relations Okay. Thanks,Marion.Nextquestion,please. 瑞安·克罗 - 投资者关系高级副总裁好的。 谢谢，玛丽恩。下一个问题，请。 TerenceFlynn-MorganStanley-Analyst 特伦斯·弗林 - 摩根士丹利 - 分析师 Hi. Thanksfortakingthequestion. George,youmentioned,itsoundslike,likely, youandSanofi aregoingtodoanother Phase 3trialhereforIL-33 in COPD. Can you just talk about any new insights you might have learned that drove the differential outcome in the prior two Phase 3 trials? And thenwhatyouthinkyoucanchangeoroptimizeinathirdtrialheretoimprovethelikelihoodofsuccess?Thankyou. 你好。感谢你回答这个问题。乔治，你提到，听起来你和赛诺菲可能会在这里针对慢性阻塞性肺疾病（COPD）中的IL-33再进行一次三期临床试验。你能谈谈在前两次三期临床试验中，你们学到了哪些新见解，从而推动了不同的结果吗？然后，你认为在第三次试验中，你们可以做出哪些改变或优化，以提高成功的可能性？非常感谢。 GeorgeYancopoulos-Co-ChairmanoftheBoard,President,ChiefScientificOfficer,Co-Founder 乔治·扬科波洛斯 - 董事会联席主席、总裁、首席科学官、联合创始人 Well, due to competitive issues, I'm not going to really comment on most of your questions there. And as you said, we're going to have a meeting withtheFDAandthat'sgoingtohelpusdecideonourstrategygoingforward. 嗯，由于涉及竞争问题，我不会对你们提出的大多数问题做出具体评论。正如你们所说，我们将与美国食品药品监督管理局（FDA）会面，这将有助于我们决定未来的战略方向。 Ryan Crowe - Senior Vice President-Investor Relations Okay.Thankssomuch,George.Nextquestion,please. 瑞安·克罗 - 投资者关系高级副总裁 好的，非常感谢，乔治。请提出下一个问题。 Tyler Van Buren - TD Cowen - Analyst 泰勒·范布伦- TD Cowen - 分析师 Good morning. Congratulations on the quarter. Can you elaborate on the probability of the late December decision on the RVO and every-four-week dosing filing with the new filler resulting in an approval? And just a quick follow-up would be, is this the same alternate filler that you use for the recent Libtayo adjuvant cutaneous squamous cell carcinoma approval? 早上好。恭喜您获得这一季度的好成绩。您能详细说明一下12月底关于RVO和每四周给药一次的申请，以及使用新填充剂后获得批准的可能性吗？另外，我想快速跟进一下，这是您最近用于Libtayo辅助治疗皮肤鳞状细胞癌批准的同一种替代填充剂吗？ LeonardSchleifer-Co-ChairmanoftheBoard,President,ChiefExecutiveOfficer,Co-Founder 伦纳德·施莱弗 No, it's a different filler. It's a complicated sort of timeline here. Because the new filler has to undergo its review and it’s probably in an inspection andreview, andit'sunclearwhenthatwouldbe done.Ideally,ifthatcouldgetdone before our November timeline for the approval, forthe PDUFA datefortheRVO/Q4,thatwouldreallybeperfect,andwecouldgetitallwrappedupinlateNovember. 不，这是另一种填充剂。这里的时间线有些复杂。因为新的填充剂必须经过审查，而且很可能正处于检查和审查阶段，目前尚不清楚何时能完成。理想情况下，如果能在我们11月的审批时间表之前，即在RVO/Q4的PDUFA日期之前完成，那就太好了，我们可以在11月底全部搞定。 IfitturnsoutthattheyhavetogotoDecember togetthefillerapproved,hopefully,thatwouldbeasfarastheyhavetogo.Butofcourse,theFDA looksatallthesethingsprettycarefully.Thisfillerhasaverygoodtrackrecord,butit'sgottoundergotheinspectionandsoforth.SoIsuspectthat If theygot through thatin December, then we could rapidly resubmit ormaybe the application wouldstill be on file, we don't knowexactly. We're goingtohavediscussionswiththeFDA.Butwebelievethatthereisnothinglefttodoonthatapplicationotherthantogetthefillerinplace. 如果最终等到12月才能获得填充剂的批准，希望那将是他们必须做的全部工作。当然，FDA会非常仔细地审查所有这些事项。这种填充剂有良好的记录，但它必须接受检查等程序。所以我猜测，如果他们在12月通过了这些程序，那么我们可以迅速重新提交申请，或者申请可能仍在审核中，我们并不确切知道。我们将与FDA进行讨论。但我们相信，除了让填充剂到位之外，这项申请已经没有其他事情需要做了。 Sowethinkwe'vehadverygooddiscussionsaboutlabelandindicationsandall,that'sfine.Butit'snotoveruntilit'sover,obviously. 所以，我们认为我们已经就标签和适应症等问题进行了很好的讨论，这很好。但显然，事情没结束之前，一切皆有可能。 Butideally,tosummarize,ifwecouldgetthefiller onlinebeforethelateNovemberdate,itcouldall be wrappedup then.Ifnot,we wouldexpect and hopethat that filler would get approved in December.Andthen rapidly,we would immediately resubmit and the FDA hopefully could act immediately.That'sto-datethatwecantellyou. 但理想情况下，概括来说，如果能在11月底之前让填充剂到位，那么一切就都能搞定。如果不能，我们期望并希望该填充剂能在12月获得批准。然后我们会迅速立即重新提交，希望FDA能立即采取行动。这就是我们目前能告诉你们的。 Ryan Crowe - Senior Vice President-Investor Relations Yes. Thanks, Len. Complicated situation. Let's move to the next question, please. 瑞安·克罗 - 投资者关系高级副总裁 是的。谢谢，莱恩。情况很复杂。请让我们继续下一个问题。 EvanSeigerman-BMOCapitalMarkets-Analyst 埃文·西格曼 - BMO资本市场 - 分析师 Hi, guys. Thank you so much for taking my question. Just taking a step back, can you walk me through some of the internal changes you've made withyour regulatory manufacturing teams toprevent the CRLs that we've seen ofrecent andensurethatproducts thatshouldbeapproved get approvedandgetthepatientsasquicklyaspossible?Thankyou. 大家好。非常感谢你们回答我的问题。退一步来说，你们能否给我介绍一下，你们对监管制造团队做出了哪些内部调整，以防止近期出现的药品被拒绝（CRL）的情况，并确保应获批的产品能尽快获批并交付给患者？非常感谢。 LeonardSchleifer-Co-ChairmanoftheBoard,President,ChiefExecutiveOfficer,Co-Founder 伦纳德·施莱弗 Nowthat'saverypointedquestion. AndIreallywanttoaddressitheadon.Theissues thatwehavehadhavenotbeeninternalregulatoryproblems. WehaveaterrificrelationshipwiththeFDA.OurregulatoryteamincludespeoplewhousedtoworkattheFDAorpeoplewho'vebeeninthe industry doing this for decades.There's no shortage of expertiseor relationshipson a regulatoryfront. We've certainly askedthat question,the Boardalwaysaskthatquestion,andthere'snoissuethere. 这个问题问得非常尖锐。我真的很想直接回答。我们遇到的问题并非内部监管问题。我们与美国食品药品监督管理局（FDA）的关系非常好。我们的监管团队中既有曾在FDA工作过的人，也有在这个行业从业数十年的人。在监管方面，我们并不缺乏专业知识或人脉。我们当然问过这个问题，董事会也总是问这个问题，这方面没有问题。 On the manufacturing front, we recognize that it would be more ideal if we could have our own filling. We would have expected to have that by now, but we gotdelayeddramaticallyduring COVID because ofsupplychain issues in manufacturing. As Isaid, we hope thatfillingwill come online nextyear. 在生产方面，我们认识到，如果我们能拥有自己的灌装生产线，那将更为理想。我们原本预计现在就已经实现了，但由于疫情期间生产供应链出现问题，我们的进度被大幅推迟。正如我所说，我们希望灌装生产线能在明年投入使用。 Intermsofgettingbackupsandwhathaveyou,it'sarelativelycomplicatedsituation.We'vebeenworkingonbackupsforquitealongtimenow. Theproblem, asyoumightimagine, isthat, forgoodreason,theFDAisveryfinickyaboutshowingwhereyoumake, goingtomakethe product,literally,whatequipmentit'sgoingtotouch,andthenyouhavetodostabilitytesting,andqualitytesting.Allofthatforagivenfiller.And thattakesquiteabitoftime,quiteabitofresources. 在获取备选项及其他相关事宜方面，情况相对复杂。备选项方面，我们已投入相当长的时间。可能你能想象到，问题在于，出于合理的原因，美国食品和药物管理局（FDA）对于展示产品的生产地点、实际生产过程、设备接触情况等要求非常严格，此外，还需对给定的填充剂进行稳定性测试和质量测试。所有这些都需要相当长的时间和资源。 Soinsummary,Idon'twanttosound[defensive]atall.Wehavelookedatthis.Itisnotaregulatoryproblemforus.Itis,insomerespects,a manufacturingissueintermsofgettingonlineourownfilling.Havingbackupfillersinplaceiscomplicated,we'retryingtodothat. 总之，我根本不想显得回避问题。我们已经研究过这个问题。对我们来说，这不是监管问题。从某些方面来说，这是我们自己的灌装上线方面的制造问题。安排好备用灌装机很复杂，我们正在尝试这么做。 But our biggest problem, frankly,is the FDAhas nowpaidquite abit close attention. AndI mightpoint out that the biggest companiesin the world havehadthesameissuewithfillers where even with the same filler, andthey've calledustoknowhow's itgoing?Buttheyjustdon'ttalkaboutthe CRLs thattheyget, andwe knowthat they're out there. SoI'm notsure that we're worse offin that regard.But wherever we are, I'm nothappy aboutitandwe'renothappyaboutit,andwe'retryingtorectifythesituation.Ihopethatgivesyouaglimpseintoourthinking. 但坦率地说，我们最大的问题是美国食品药品监督管理局（FDA）现在给予了相当多的关注。我可能会指出，世界上最大的公司在填充剂方面也遇到了同样的问题，即使使用的是同一种填充剂，他们也会打电话给我们询问情况。但他们从不谈论他们收到的完整回复函（CRL），而我们知道这些CRL是存在的。所以我不确定我们在这方面是否更糟。但无论我们处于何种境地，我都对此感到不满，我们也不满意，并且正在努力纠正这种情况。我希望这能让你们大致了解我们的想法。 Ryan Crowe - Senior Vice President-Investor Relations Okay. Let'smovetothenextquestion,please. 瑞安·克罗（Ryan Crowe）- 投资者关系高级副总裁好的。请继续下一个问题。 BrianAbrahams-RBCCapitalMarkets-Analyst 布莱恩·亚伯拉罕 - 加拿大皇家银行资本市场 - 分析师 Goodmorning. Thanksfortakingmyquestion. JustonthepipelinefrontontheFactorXIantibodyprogram.Idon'twantyoutofrontrunyour roundtable, but I knowyouguys recently startedalargePhase 2studyfor the antibodies in afib.SoI'm just curious what youguys are looking for out of that studyandmaybe out of other Factor XIsindevelopmenttomoveintoregistrationals in that andother large indications andreallyacceleratethatprogram?Thanks. 早上好。感谢您回答我的问题。我想了解一下关于Factor XI抗体项目的研发进展。我不想让您提前结束圆桌会议，但我知道你们最近启动了一项针对房颤（afib）患者的大型二期抗体研究。所以我只是很好奇，你们期望从这项研究中获得什么？此外，对于其他的在针对该适应症及其他大型适应症的，处于研发阶段并有望进入注册性临床试验的 XI 因子药物，你们又有何期待？以及，如何才能真正推进该项目的进程？谢谢。 GeorgeYancopoulos-Co-ChairmanoftheBoard,President,ChiefScientificOfficer,Co-Founder 乔治·扬科波洛斯 - 董事会联席主席、总裁、首席科学官、联合创始人 Well, the Phase 2studyisarunning studyintowhatwe anticipatetobe our Phase 3pivotal program there. Andwe are inpivotal programs inother settings where anticoagulation can be important. And of course, what are we looking at? We're trying to understand as well as we can the benefit riskratioforourtwodistinctantibodies. 第二阶段的研究是一项持续进行的研究，旨在为第三阶段的关键项目做准备。此外，我们在其他可能对抗凝治疗至关重要的情形中也开展了关键临床试验项目。当然，我们关注的是什么？我们正竭尽全力，试图了解我们两种不同抗体的获益风险比。 Wethink,inthisprogram,it'sallgoingtobeaboutbenefitrisk.Wethinkthatfranklyinsomeways,decreasesinbleedingriskaregoingtobefranklymoreimportantthan,insomecases,theanticoagulationeffect.Aslongasyouhaveanticoagulanteffect,butifyouhavereallyasafewayof achievingit,wethinkthere'saplethoraofsettingswherethesetwoantibodiescanrespectivelyfindtheirplace.Andparticularly,inpatientsmaybe even much larger than the [SPAF]indication where,right now, useofanticoagulantsis verylimitedbecause ofthe bleeding concerns. That's what's reallylimitingtheutilizationofanticoagulantsmorewidelyacrossmany,many,manymoresettings. 我们认为，在这个项目中，一切都将围绕“获益与风险”展开。坦率地说，在某些方面，降低出血风险的重要性在某些情况下甚至会超过抗凝效果。只要你有抗凝效果，但如果你有真正安全的方法来实现它，我们认为这两种抗体在许多情况下都能各有所用。特别是在患者数量可能远超[SPAF]适应症的情况下，目前由于出血风险问题，抗凝药物的使用非常有限。这才是真正限制抗凝药物在更多情况下更广泛使用的原因。 And so we think that our approach using two antibodies is going to allow us to really customize and tailorize how individualpatients are treated, where we can optimize, we can pick the antibody perhaps with the least bleeding risk for the patients who are most concerned about that while providingadifferentantibodywithmaybehigheranticoagulationcapabilitywhenthat'sneeded. 因此，我们认为，我们适用两种抗体的策略将使我们能够真正为每位患者量身定制治疗方案，在优化治疗的同时，我们可以为最担心出血风险的患者选择出血风险最小的抗体，而在需要时，则可以使用抗凝能力更强的不同抗体。 So we think there's a lot of opportunities here beyond [SPAF]. We think that's where the major opportunity is today. We do not think that's where the major opportunity is going to be going forward in the future. We're going to where we think the future is not necessarilywhere the current is rightnow. 因此，我们认为除了[SPAF]之外，还有很多机会。我们认为SPAF是当前的主要机遇所在。但我们并不认为这是未来主要机遇所在。我们将前往我们认为未来所在之处，而那里未必是当前所在之地。 Leonard Schleifer - Co-Chairman of the Board, President, Chief Executive Officer, Co-Founder 伦纳德·施莱弗 And in the future, we'll be having a roundtable to tell him about that. 将来，我们会举行一次圆桌会议，向他介绍这件事。 Ryan Crowe - Senior Vice President-Investor Relations  Correct.November 10. Thanks, George. Let's move to the next question, please. 瑞安·克罗 投资者关系高级副总裁  没错。11月10日。谢谢，乔治。请继续下一个问题。 CarterGould-CantorFitzgerald-Analyst 卡特·古尔德 - 坎托·菲茨杰拉德 - 分析师 Good morning. Thanks for taking the question. Len, you highlighted the sort of the meager matching thus far with the foundation and I guess you framed it remaining committing to that funding until the end of the year, which I guess sort of allude to a potential terminus. At some point, maybe at the start of the year, does it warrant taking a different tact if you don't see any other people match your commitment? 早上好。感谢你回答这个问题。Len，你强调了基金会迄今为止匹配的资金相当有限，我猜你这么说是在暗示基金会可能会在今年年底前继续提供这笔资金。那么，如果到某个时候，也许是在年初，你发现没有其他人愿意匹配你的承诺，是否应该采取不同的策略呢？ LeonardSchleifer-Co-ChairmanoftheBoard,President,ChiefExecutiveOfficer,Co-Founder 伦纳德·施莱弗 Yeah.Imean,I'dlikenottotellpeopledon'tbothertomakeacommitmentbecausewe'regoingtotakecareofit.That'snotourapproach.Our approachwillbethatwewilllookatitfreshnextyearandseewhatthebeststrategyistohelppatients.Goodquestionthough. 是啊。我的意思是，我不想告诉人们不要费心做出承诺，因为我们会负责到底。这不是我们的做法。我们的做法是，明年我们会重新审视这个问题，看看什么才是帮助患者的最佳策略。不过，这个问题问得很好。 Ryan Crowe - Senior Vice President-Investor Relations Thanks,Len.Let'smovetothenextquestion,Shannon. 瑞安·克罗（Ryan Crowe）- 投资者关系高级副总裁谢谢，莱恩。香农，让我们继续下一个问题。 CoryKasimov-EvercoreISI-Analyst 科里·卡西莫夫 - Evercore ISI - 分析师 Good morning, guys. Thanks fortaking the question. So on the heels of your positive Phase 3 data for cemdisiran, can you outline how you see the commercialopportunityevolvingforgMGandwhatyourplansareinEuropewiththisasset?Thankyou. 早上好，各位。感谢你们回答这个问题。那么，在cemdisiran第三阶段数据表现积极之后，你们能否概述一下你们如何看待gMG的商业机会演变，以及你们在欧洲对该资产有何计划？非常感谢。 LeonardSchleifer-Co-ChairmanoftheBoard,President,ChiefExecutiveOfficer,Co-Founder 伦纳德·施莱弗 Beforewegettothat,maybe,George,couldyoujustremindeverybodywhat'soutthereandwhatthelimitations ofthecurrenttherapies are? BecauseI'mnotsureeverybody'sonthesamepageonthat. 在我们讨论这个之前，乔治，也许你能提醒一下大家，目前市面上有哪些疗法，以及这些疗法的局限性是什么？因为我不确定大家对此是否都有共识。 GeorgeYancopoulos-Co-ChairmanoftheBoard,President,ChiefScientificOfficer,Co-Founder 乔治·扬科波洛斯 - 董事会联席主席、总裁、首席科学官、联合创始人 Well,rightnow,therearetwomajorclassesthatarebeingutilizedinthisspace.One,ofcourse,istheC5class.TheotheristheFcRnclass.Interms of the C5 class, as we know, most of those areadministered using these large intravenousinfusions which are very inconvenient for the patients. 目前，这一领域主要使用两大类。当然，一类是C5类。另一类是FcRn类。就C5类而言，众所周知，其中大多数是通过大型静脉注射给药，这对患者来说非常不便。 And in terms of the FCRN class, those are given via also intravenous infusions approaches right now or ultimately, they may move to large-volume subcutaneous approaches that are also somewhat difficult to self-administer. But in any case, the issues also have to do with safety and efficacy. 就FCRN类而言，目前这些药物也是通过静脉注射给药，或者最终可能会转为大容量皮下注射给药，而后者在自我给药方面也有些困难。但无论如何，这些问题都与安全性和有效性有关。 Thethingthat'sexcitingaboutourprogramisunliketheFcRnswhich,eitherwhenyouuseweeklytreatment,yougetlessbenefits,atleastcross-studies, from these standard scores; or with the episodic treatment where you have a U-shaped curve where the patients respond deeply,butthen,almostrevertbacktobaselinebeforeyougivethemtheirnextdose. 我们项目令人兴奋的一点是，与FcRns不同，无论是采用每周治疗，还是采用间歇性治疗，从这些标准评分来看，至少在交叉研究中，你获得的益处都较少。在采用间歇性治疗时，会出现U型曲线，患者反应强烈，但随后几乎会恢复到给药下一剂之前的基线水平。 TheC5sallowyoutohavestabledeepcontrolthroughtheentiredosingperiod.Andcross-studycomparison,ouragentseemstohave,intermsofthestandardmeasurethatisbeingusedtoevaluatethese,thebestcross-trialefficacythat'sstableandcontinuousthroughoutthedosingperiod. C5s让您在整个给药期间都能保持稳定的深度控制。通过交叉研究比较，我们的药物在用于评估这些药物的标准指标方面，似乎在整个给药期间都表现出稳定且持续的最佳交叉试验疗效。 Now, oneimportant feature of all of these agents, obviously, is they all work by suppressing the immune system throughvarious degrees, eithertheFcRnsortheC5viatheirinhibitionofthecomplementcascade,theybothresultpotentiallyconcernswithefficacy,inthecaseoftheC5smostly, meningococcal infections. As you've probably seen with theFcRn class, with longer usage, they'veseen serious infections, for example, resurgence ofEBVandevenfatalEBVinfections.Sothoseareconcernswitheverythingthat'savailableintheclass. 显然，所有这些药物的一个重要特征是，它们都通过不同程度的抑制免疫系统来发挥作用，要么是通过抑制Fc受体（FcRns）来抑制免疫系统，要么是通过抑制补体级联反应来抑制C5。这两种药物都可能引发疗效方面的担忧，尤其是对于C5抑制剂，可能会引发脑膜炎球菌感染。正如你可能已经从FcRns类药物中观察到的，长期使用这类药物会导致严重感染，例如EBV（爱泼斯坦-巴尔病毒）复发，甚至致命的EBV感染。因此，这类药物中的所有药物都存在这些担忧。 The thing that's exciting about our program is not only do we seem to have, at least, potentially best-in-class and stable efficacy with dosing using the most convenient dosing regimen which is subcutaneousonce-every-three months.Nothing likethat'sever been seen for this class deliveringthissortofefficacy.Butbecauseweonlypartiallyinhibitthecomplementpathway,thereisthepotentialwhichwewillhavetogetdatatosupport goingforwardthatmayoffercertainsafetybenefitsforpatients. 我们项目令人兴奋之处在于，我们似乎至少拥有同类最佳且稳定的疗效，而且采用最方便的给药方案，即每三个月皮下注射一次。这一疗效在同类药物中前所未有。但由于我们只是部分抑制了补体途径，未来我们还需要数据来支持，这可能会为患者带来一定的安全益处。 So the exciting thing about the program is we certainly have the most convenient dosing regimen, we seem to have the most consistent efficacy with cross-study comparisons, the deepest control. And the factthat we don't completely inhibit the targetin this class, there isthe long-term opportunitythatwemaybeabletoshowthatwemayhavebettersafetyforpatientsaswellhere. 因此，该计划令人兴奋之处在于，我们无疑拥有最方便的给药方案，通过跨研究比较，我们似乎展现出了最稳定的疗效，且控制力度最大。此外，由于我们并未完全抑制这类药物的目标，因此从长远来看，我们或许能够证明，此类药物对患者而言具有更好的安全性。 So it's a very exciting profile, I think, potentially be able to deliver for this class of patients who are really needing better treatments in terms of convenience,intermsofefficacy,butalsointermsofsafety.Marion? 所以我认为，这是一个非常令人兴奋的方案，可能能够为这类患者提供更好的治疗，不仅在便利性、疗效方面，而且在安全性方面。玛丽恩，你怎么看？ MarionMcCourt-ExecutiveVicePresident-Commercial 玛丽昂·麦考特 - 商业执行副总裁 Sure. Soeverything we're doingin the launch strategy forcommercialization isbased onthe very encouraging clinical profile that George is describing. Sowe're veryexcitedabout this opportunity. We will be launch-ready andwe dofeel for thisreally important category in patients with unmetneedthatwepotentiallyhaveaveryhighlydifferentiatedproducttobringintothemarketplace. 当然。我们在商业化推广策略中所做的一切，都是基于乔治所描述的非常鼓舞人心的临床特征。因此，我们对这次机会感到非常兴奋。我们将做好上市准备，并且我们确实认为，对于这一需求未得到满足的重要患者群体，我们有可能将一款极具差异化的产品推向市场。 Ryan Crowe - Senior Vice President-Investor Relations Thanks,GeorgeandMarion.Let'smovetothenextquestion,please,Shannon. 瑞安·克罗 - 投资者关系高级副总裁 谢谢乔治和玛丽恩。香农，请继续下一个问题。 SimonBaker-Rothschild&CoRedburn-Analyst 西蒙·贝克 - 罗斯柴尔德与科雷德本公司 - 分析师 Thankyouverymuchfortakingmyquestion. Myfirsteverquestiononthecall.Ijustwantedtogobacktoyourcomments,George,onintravitreally deliveredCD3.You'retryingitinitiallyinuveitis.IjustwonderwhatthescopeofyourambitionwasinthatsettinggiventheroleofTcellinfiltrationinglaucomawhichis,obviously,amuchbiggerindication.Anythoughtsonwherethiscouldgowillbemuchappreciated.Thankyou. 非常感谢您回答我的问题。这是我第一次在电话会议上提问。我想回到您之前关于玻璃体内注射CD3的评论，乔治。您最初是在葡萄膜炎中尝试这种方法。鉴于T细胞浸润在青光眼中的作用，青光眼显然是一个更大的适应症，我想知道您在这一领域的目标是什么。如果您能分享一下对此发展方向的看法，我将不胜感激。非常感谢。 George Yancopoulos - Co-Chairman of the Board, President, Chief Scientific Officer, Co-Founder 乔治·扬科波洛斯  - 董事会联席主席、总裁、首席科学官、联合创始人 I didn't hear what you said about glaucoma. What glaucoma? 我没听见你说什么青光眼。什么青光眼？ SimonBaker-Rothschild&CoRedburn-Analyst 西蒙·贝克 - Rothschild & Co Redburn - 分析师 So there's some evidencethat glaucoma is caused,greater or less part,by T cell infiltration in the eye. So I just wondered if using CD3 antibodies inthissettingwouldpotentiallyencompassthatindicationaswellasuveitis. 有证据表明，青光眼在一定程度上是由眼部T细胞浸润引起的。所以我想了解，在这种情况下使用CD3抗体是否也能涵盖这一适应症以及葡萄膜炎。 GeorgeYancopoulos-Co-ChairmanoftheBoard,President,ChiefScientificOfficer,Co-Founder 乔治·扬科波洛斯 - 董事会联席主席、总裁、首席科学官、联合创始人 Yeah.We'revery excited aboutourCD3 antibodyprogram,asyou mentioned.Webelievethatthisistheworld'sfirstcompleteblockerofCD3 orTcell function that'sever beenevaluatedintheclinic.Therehavebeenpartialblocker, partialagonistto-date.Wethink that goinginto theeyein uveitis which a lot of data suggests thatmost, ifnot all, of these uveitis are related to T cells. 是啊。正如您所述，我们对我们的CD3抗体项目感到非常兴奋。我们认为，这是世界上首个在临床上经过评估的完全阻断CD3或T细胞功能的药物。迄今为止，已有部分阻断剂和部分激动剂。我们认为，将其用于治疗葡萄膜炎是合理的，因为大量数据表明，大多数（如果不是全部）葡萄膜炎都与T细胞有关。 If we can block the T cells locallywithout, becausethe doses that we're going to be using are very low, they're not going tobe having systemic effects, you can have really profound benefits in this high unmet need without subjecting patients to any sort of global or systemic immunosuppression. 如果我们能在局部阻断T细胞，且由于即将使用的剂量非常低，不会产生全身性影响，那么在满足这一巨大未满足需求方面，将能获得真正深远的好处，同时患者也不会遭受任何全身性或系统性免疫抑制。 Sowereallythinkthisisaverynovel,verydifferentapproachtoactivenon-infectiousuveitis.Wethinkit'stheperfectsettingtotryourCD3antibody. 因此，我们确实认为这是一种针对活动性非感染性葡萄膜炎的非常新颖且与众不同的方法。我们认为这是尝试我们的CD3抗体的理想领域。 Wehavebeenworkingalotonglaucoma.I'mgladthatyoubroughtitup.Ibelieve,basedonourRegeneronGeneticCenter,whichareworldleadersinunderstandingthegeneticbasesofdisease,we've,Ithinkuncoveredthemostimportantdriversgeneticallyofglaucoma.Andwewill berollingoutintheverynearfutureourstrategyandourprogramsinaverynearclinicalprograminglaucomaaswell. 我们在青光眼领域做了大量工作。很高兴你提到了这一点。我相信，凭借我们再生元遗传中心在疾病遗传基础研究方面的世界领先地位，我们已经发现了青光眼最重要的遗传驱动因素。在不久的将来，我们也将推出针对青光眼的临床项目，并公布我们的战略和计划。 SoI'mgladyoubroughtitup.I'mgladyou'reinterestedinit.Butthesearegoingtobetwoverydifferentdistinctprograms.We're goingtohave our CD3 program for non-infectious uveitis.And we're going to be rolling out a very special and very exciting programin glaucoma based entirelyon our internally discovered genetics capabilities. We think that these programs really have the opportunity to create entirely new franchises in ophthalmology.Thewaywethinkaboutit,onecouldbetheEYLEAforuveitis;theothercouldbetheEYLEAforglaucoma.Sostaytuned. 很高兴你提到了这一点。我很高兴你对这个感兴趣。但这两个项目将会有很大的不同。我们将为非感染性葡萄膜炎推出我们的CD3项目。同时，我们即将推出一项针对青光眼的特别项目，该项目极具突破性—其研发完全依托于我们自主发掘的遗传学技术能力。我们认为，这些项目真的有机会在眼科领域创造全新的产品线。我们的想法是，一个可能是针对葡萄膜炎的EYLEA；另一个可能是针对青光眼的EYLEA。所以请继续关注。 RyanCrowe -SeniorVicePresident-InvestorRelations  Thank you, George. Veryexciting. I think wehave time for threemore questions, Shannon. 瑞安·克罗  - 投资者关系高级副总裁 谢谢，乔治。非常令人兴奋。香农，我想我们还有时间回答三个问题。 AlexandriaHammond-WolfeResearchLLC-Analyst 亚历山大·哈蒙德 - 沃尔夫研究有限责任公司 - 分析师 Thanks for taking the question. On the upcoming Libtayo LAG-3 readout, it seems like the goalis to outperform Opdualag. But could you share yourconfidenceindemonstratinga[stat-sig]benefitagainstKeytruda?Andasafollow-up,canyoutellusalittlebitmoreabouttheopen-label Phase3trialyouhaveongoingagainstOpdualag?Isitjustanothershowofconfidencethatyourcombocanbemorepotentthanthecurrentlyapprovedoption? 感谢您回答这个问题。关于即将公布的Libtayo LAG-3数据，看起来目标是超越Opdualag。但您能否分享一下您对Libtayo相较于Keytruda具有[统计学显著]优势的信心？另外，能否再介绍一下您正在进行的针对Opdualag的开放标签III期试验？这是否只是再次证明您的组合方案比目前获批的方案更有效？ GeorgeYancopoulos-Co-ChairmanoftheBoard,President,ChiefScientificOfficer,Co-Founder 乔治·扬科波洛斯  - 董事会联席主席、总裁、首席科学官、联合创始人 A lot of questions in there. But first and most importantly, our study is ongoing. As you said, we are trying our combination versus Keytruda. Our hopeisthattheKeytrudawillbehaveasithasmoreorlesshistorically.Andourhopeisthat,remember,wehavetwoarmsinthestudy,alowdoseandthehighdose,thatthetwoarms,atleastoneofthem,willbehavebetterthantheKeytrudaarm. 这里面有很多问题。但首先也是最重要的是，我们的研究正在进行中。正如你所说，我们正在尝试我们的组合疗法与Keytruda的对比。我们希望Keytruda的表现能大致与以往相同。而且我们希望，记住，我们的研究有两个组，低剂量组和高剂量组，至少其中一个组的表现会比Keytruda组更好。 The way we power the study isthat we poweredit to notonly hit PFS andOS.And with the minimal expectation thatif we have Opdualag-like activity,we'vepoweredthestudysothatwecanwininbothPFS,butalsowhereOpdualagfailedinOS. 本研究的检验功效（power）设计为：我们不止于对无进展生存期（PFS）和总生存期（OS）这两个终点进行检验，并且有一个最低预期——若本药物能达到类似 Opdualag 的活性水平，我们的试验设计将确保不仅能在 PFS 终点上取得阳性结果，还能在 Opdualag 曾失败的 OS 终点上取得成功。 If, as you mentioned,wehavebetterdata thanOpdualag,thenobviously,wewillsignificantlywin evenmore thanthat.So we've powered the studyforaminimalofOpdualag-likebenefit,butsoastohavealargeenoughOSsignalsothatwewillwinwithcomparabledatathere. 如您所述，如果我们拥有比Opdualag更好的数据，那么显然，我们的优势将远超于此。因此，我们为这项研究提供了至少与Opdualag相当的效益，同时确保OS信号足够大，以便我们在数据相当的情况下也能胜出。 Ofcourse, the datawill speakfor itself. We'll see whether or notwe endup having better efficacythan Keytruda, better efficacycross-study comparisonthanOpdualag,andsoforth.Butwecontinuetobeexcitedobviouslyaboutthisprogram.There'sobviouslyahighneedhere.Therewas veryexcitingearliertrialdatausingourfianlimabantibody.Andsowe areanxiousbutexcitedaboutawaitingthedatareadoutnextyear. 当然，数据会自己说话。我们会看看我们的疗效是否优于Keytruda，是否在跨研究比较中优于Opdualag等等。但我们显然对这个项目仍然充满期待。这里显然有很大的需求。之前我们的fianlimab抗体的试验数据非常令人兴奋。因此，我们既焦急又兴奋地等待着明年的数据结果。 Ryan Crowe - Senior Vice President-Investor Relations Yeah. First half of next year is the timing on that. Shannon, next question, please. 瑞安·克罗（Ryan Crowe）- 投资者关系高级副总裁 是的。明年上半年是合适的时间。香农，请提出下一个问题。 ChristopherSchott-JPMorgan-Analyst 克里斯托弗·肖特 - 摩根大通 - 分析师 Great.Thankssomuch.Justaquickoneonthelaunchoflinvoseltamab. Justhow'sthatprogressingversusexpectations?Andcanyoujustelaboratea bit onthe timelinesof when you could actually get this product into someof those earlierlines of therapy giventhe profile that seems to be shapinguphere?IsthereanabilitytopullthatforwardoracceleratethatallintermsofworkingwithFDA,etcetera?Thankyou. 太棒了非常感谢。我想快速问一下关于linvoseltamab的上市商业化情况。与预期相比，进展如何？鉴于目前的产品轮廓似乎正在成型，您能否详细说明一下这款产品各前线疗法何时能上市？与FDA等合作，是否有能力提前或加快这一进程？非常感谢。 MarionMcCourt-ExecutiveVicePresident-Commercial Marion McCourt - 商业执行副总裁 SoIcan take the first portion onthe launch andthenI'm sure George will come in on therest.But certainly, it's earlydays. But as Imentioned, the progress has been very, very good. We've seen the typical indicators when you have a successful launch ongoing. Physician feedback has been veryfavorable. Our formularylistings, pathwayinclusion, REMSrequirements, payer coverage. Sowe are pleasedwith thatwe're seeingsofar. And certainly,theenthusiasmof thehematologycommunityforLynozyficishigh. Keepinginmindthis isthe fifthlinesettingformultiplemyeloma patients,soaheavilypretreatedpopulation.ButtoGeorgeforearlierlines. 我可以回答关于产品上市部分的问题，然后我相信乔治会接手后续的部分。当然，现在仍处于早期阶段。但正如我提到的，进展非常非常顺利。我们已经看到了成功开启商业化时通常会出现的典型指标。医生的反馈非常积极。我们的处方集列表、路径纳入、风险评估和缓解策略（REMS）要求、以及支付方覆盖范围等方面都表现良好。因此，我们对目前所看到的一切感到满意。当然，血液学界对Lynozyfic的热情也很高。请记住，这是多发性骨髓瘤患者的第五线治疗，因此患者群体已经经过了大量的预处理。交给乔治关于更早线治疗的问题。 GeorgeYancopoulos-Co-ChairmanoftheBoard,President,ChiefScientificOfficer,Co-Founder 乔治·扬科波洛斯 - 董事会联席主席、总裁、首席科学官、联合创始人 Well, we believe that if one looks at the totality of the data, certainly, if it was me or somebody that I cared about, giving the late-stage patients anyofthesetreatments,Ithink,Lynozyficwouldbethechoicebasedonalltheavailabledataoutthere. 嗯，我们认为，如果从整体数据来看，当然，如果是我或我关心的人，要给晚期患者提供这些治疗中的任何一种，我认为，基于现有的所有数据，Lynozyfic会是首选。 And importantly, what this says, if it looks like it has the potential for impressively more benefit in the late-line patients, that of course suggests thatitshouldhavealsothebestbenefitfortheearlier-stagepatients.Becauseofthat,we'vetakenonalotofveryaggressiveprogramsintheearly stages,not only infirstline myeloma and insecond linemyeloma,but inthepre-malignantsettings.As I summarized,wenow havedata inmostofthesesettings,eitherasmonotherapyorinverylimitedcombinations,mostofwhichwe'venowpresentedtovaryingdegrees. 重要的是，这表明，如果它在后线患者中显示出具有令人印象深刻的更大获益潜力，那么当然也意味着它对早线患者应具有最佳获益。因此，我们在早期阶段采用了许多非常积极的治疗方案，不仅用于一线和二线骨髓瘤治疗，还用于癌前病变的治疗。正如我所总结的，我们现在已掌握这些治疗情景中的大多数数据，无论是作为单一疗法还是非常有限的联合疗法，其中大多数数据我们已在不同程度上进行了展示。 And the data really is stunning and unprecedented. We're having a high rate of seeing molecular complete responses in smoldering in, amyloidosis whichisapremalignantcondition,butwheretheproteinmadebytheabnormalcellscancauseproblems.Onceagain,unprecedentedmonotherapy activityinthefirstlinesetting, we'vedescribedthat.Andinlater-linesettings,with newcombinations thatwe'realsotrying,unprecedentedlevels ofactivity. 这些数据确实令人震惊，前所未有。淀粉样变性是一癌前病变但异常细胞产生的蛋白质会引起诸多问题，在淀粉样变性中，我们观察到很高的分子完全缓解率。我们再次描述了一线治疗中前所未有的单一疗法活性。在后续治疗中，我们也在尝试新的组合疗法，其活性达到了前所未有的水平。 So we think that this program really has the potential tochange the face of treatment for these disease indications in all of its manifestations, whether it be premalignant precursor settings, whether it's early-linedisease, whether it's second-linedisease, or whether it's for the late-stage patients. 因此，我们认为这一项目确实有潜力改变这些疾病适应症在所有表现形式上的治疗面貌，无论是癌前病变、早期疾病、二线疾病，还是晚期患者。 So I thinkthis is an exciting time for the field. And I just want to remind you that in many ways, our odronextamab programis quite similar in that particular in follicular lymphoma where we look like we have the best late-line data, we're going aggressively in earlier-linedisease. And once again, we've released the data-leading cohorts of Phase 3s as monotherapy and so forth. Once again, unprecedented efficacy in these small initial cohorts that we're looking at which really get us excited that these bispecifics really have the chance to really change the hematologic oncologyspaceintheirrespectivesettings. 所以我认为，对于这个领域来说，这是一个激动人心的时刻。我想提醒大家，在许多方面，我们的odronextamab项目与滤泡性淋巴瘤的治疗非常相似，在滤泡性淋巴瘤的治疗中，我们似乎拥有最佳的晚期治疗数据，同时也在积极推进早期治疗。我们再次发布了数据领先的III期单药治疗队列等。在这些小规模的初步队列中，我们再次看到了前所未有的疗效，这让我们非常兴奋，因为这些双特异性抗体确实有机会在各自的领域真正改变血液肿瘤学。 LeonardSchleifer-Co-ChairmanoftheBoard,President,ChiefExecutiveOfficer,Co-Founder 伦纳德·施莱弗 Letmejustsay,beforewegotothenextquestion,oneisIthinkinherenttowhatGeorgeissayingthereisthatallbispecificsarenotcreatedequal. Theteamspendsanenormousamountoftimewithallthetechnologyathandtoselectandcreatebispecificsthatwethinkaredifferent,fundamentallydifferent.Andthat'swhywethinkwe'reseeingbetterdata. 在进入下一个问题之前，我想说的是，我认为乔治（George）刚才的话中隐含的一个观点是，并非所有双特异性抗体都是一样的。我们的团队花费了大量时间，利用手头的所有技术，来选择和创造我们认为与众不同、根本不同的双特异性抗体。这就是为什么我们认为我们看到了更好的数据。 Ijustalsowanttoemphasize,we'remakingahugecommitmenthere.Weexpecttoconductasmanyas10registrationoftrialsforLynozyficincluding,asGeorgeoutlined,abroadregistrationprograminfrontline orevenearlier myelomapatients,bothfortransplanteligibleandineligible. This is abigspace. It's a$30billion market potential. Darzalex alone is annualizing at$15billion. Yousawsome cross-studydatathatsuggests that wecanoutperform.We'vehadsomesuccesswhereDarzalexhasalreadyfailedintheIgAspace.Andwe'vehadsomesuccessincross-studycomparisonsinthesmoldering. 我也想强调一下，我们在此做出了巨大的承诺。我们预计将为Lynozyfic进行多达10项注册试验，包括乔治（George）所概述的，针对一线甚至更早期骨髓瘤患者（无论是否符合移植条件）的广泛注册计划。这是一个很大的市场空间，具有300亿美元的市场潜力。仅Darzalex一项的年销售额就达到150亿美元。你们看到的一些跨试验研究数据表明，我们的表现可能会更胜一筹。在Darzalex在IgA领域失败的地方，我们取得了一些成功。在惰性病变的跨临床研究比较中，我们也取得了一些成功。 SoIthinkthisisprettyexciting.AsGeorgeoutlined,it'sahugecommitment.Youexpectustospendalotandgovery--asfastaswecan.Somebodyasked about can we accelerate with the FDA. We're certainly going to talk with the FDA and advise them that we think we have the best program, how can we work together? 所以我认为这非常令人兴奋。正如乔治所概述的，这是一项巨大的承诺。你们希望我们投入大量资金，并尽可能快地推进。有人问我们能否加快与美国食品药品监督管理局（FDA）的沟通。我们当然会与FDA进行沟通，并告诉他们我们认为我们拥有最好的项目，我们如何能携手合作？ George Yancopoulos -Co-Chairman of the Board, President, Chief Scientific Officer, Co-Founder  Youmeantamyloidosis,notIgA. 乔治·扬科波洛斯- 董事会联席主席、总裁、首席科学官、联合创始人 你是说淀粉样变性，不是IgA。 Leonard Schleifer -Co-Chairman of the Board, President, ChiefExecutive Officer, Co-Founder Sorry.Imeantamyloidosis.Thankyou, 伦纳德·施莱弗- 董事会联席主席、总裁、首席执行官、联合创始人 抱歉，我的意思是淀粉样变性。非常感谢。 RyanCrowe-SeniorVicePresident-InvestorRelations Ryan Crowe - 投资者关系高级副总裁 Thankyou, Len andGeorge.Wealsolookforwardtohaving aRegeneronroundtable onLynozyfic in December ofthisyear.Solet's movetoour final question, Shannon. 谢谢，Len和George。我们也期待今年12月能就Lynozyfic与Regeneron公司进行一次圆桌会议。Shannon，接下来是最后一个问题。 SalveenRichter-GoldmanSachs-Analyst Salveen Richter - 高盛 - 分析师 Good morning. Thanks for taking my question. You spoke tonovel targets here in I&I and ophthalmology, on the GA program in particular, canyouspeaktowhattheFDAmaybelookingforpotentialstudydesigns,whetherit'sslowing[GA]lesiongrowthorvisionimprovementsand whether you need toevaluate againstcurrent agents?Andjust remind us on the I&I side whenwe might hear about these novel targets. Thank you. 早上好。感谢您回答我的问题。您谈到了I&I（感染和免疫）领域和眼科领域的新靶点，特别是关于GA（地图样变性）项目，您能否谈谈FDA可能会关注哪些潜在的研究设计，是减缓[GA]病变发展还是视力改善，以及是否需要针对现有药物进行评估？另外，请提醒我们，在I&I领域，我们何时能听到这些新靶点的消息。非常感谢。 GeorgeYancopoulos-Co-ChairmanoftheBoard,President,ChiefScientificOfficer,Co-Founder 乔治·扬科波洛斯 - 董事会联席主席、总裁、首席科学官、联合创始人 Well, interms ofGA, we'vealready designed andplanned our pivotal readout study forgeographic atrophy. We are able togo againstplacebo.Andwe'reprimarilylookingatslowingdownofgrowthtogetherwith,ofcourse,visioncontrol.AndasIsaid,wehavedatafromthecohortA from our Phase 3trial whereweexpectreadout inthesecond half of 2026which really willhelpinformwhether thisnovelsystemicapproach,which canhavealotofadvantagesintermsoftheissuesofhavingtobilaterallyinjecttwoeyesmultipletimesasopposedtobeingabletosystemically treat,we'llknowwhetherthere'sarealopportunitythereornotfromthatdata. 在GA方面，我们已经设计并规划了针对地图样变性的关键研究。我们能够与安慰剂进行对比。我们主要关注的是减缓病变发展，当然还有视力控制。正如我所说，我们拥有来自III期试验队列A的数据，预计2026年下半年将得出结果，这将有助于我们了解这种新型全身治疗方法是否真正具有机会。这种新型全身治疗方法在避免必须对双眼进行多次注射方面具有诸多优势。 IthinkthatintermsofourI&Iprograms,Ithinkyou'llprobablybehearingaboutoneofthefirstone,additionalones,additionallytotheCD3 program,whichobviouslyarerelatedI&Iandophthalmologyprogram,you'llbehearingitrolloutoverthenextcoupleofmonthswithhopefully anewclinicalprograminitiatingnextyear. 我认为，就我们的感染与免疫（I&I）项目而言，你们可能会首先听到关于其中一个新项目的消息，该项目是除CD3项目之外的另一个项目，显然与感染与免疫以及眼科项目相关。你们会在接下来的几个月里听到它的推出消息，并希望明年能启动一个新的临床项目。 RyanCrowe-SeniorVicePresident-InvestorRelations Ryan Crowe - 投资者关系高级副总裁 Okay. I appreciate everyone's patience, we wenta little over time;and appreciate yourinterestinRegeneron. Apologies tothose who remained in the Q&A queue who we did nothave achance tohear from today. As always, the Investor Relations team here atRegeneron is available to answer anyremainingquestionsyoumayhave.Thankyouonceagainandhaveagreatday. 好的。感谢大家的耐心等待，我们确实超时了一点；也感谢大家对Regeneron公司的关注。对于那些今天我们没有机会回答的仍在问答队列中的人，我向你们表示歉意。一如既往，Regeneron公司的投资者关系团队随时准备回答你们可能提出的任何问题。再次感谢大家，祝大家今天愉快。

编者按：寡核苷酸药物已成为全球新药研发的核心领域之一，近年来发展迅猛，在罕见病等多个领域得到快速应用。当前，全球超300款寡核苷酸疗法管线已进入临床开发阶段，有望在未来造福更多病患。为助力全球合作伙伴更高效地推动寡核苷酸药物从实验室走向临床，药明康德旗下WuXi TIDES平台围绕寡核苷酸、多肽及其相关化学偶联药物建立了一体化解决方案，覆盖定制合成、共价偶联、工艺开发和CMC等关键环节，赋能创新项目加速进入临床阶段。 寡核苷酸疗法持续在罕见病领域突破 寡核苷酸疗法正逐步成为罕见病治疗领域的重要突破方向。2025年第三季度，寡核苷酸疗法也持续迎来多项进展。 8月，美国FDA批准反义寡核苷酸配体偶联药物Dawnzera（donidalorsen），用于预防12岁及以上成人和儿童患者的遗传性血管性水肿（HAE）发作。据相关新闻稿，Dawnzera是FDA批准的首个用于HAE的RNA靶向药物。 9月，欧盟批准反义寡核苷酸（ASO）疗法Tryngolza（olezarsen）作为饮食控制的辅助疗法，用于治疗经遗传学确认的家族性乳糜微粒血症（FCS）成人患者。同期，该疗法用于治疗重度高甘油三酯血症（sHTG）的3期试验也迎来积极结果：每月一次的olezarsen使患者空腹甘油三酯较安慰剂平均下降72%，急性胰腺炎事件减少85%。这些进展表明，寡核苷酸疗法在罕见病治疗中的成功，为其向更广泛疾病领域的拓展奠定了基础。 此外，补体C5靶向siRNA疗法cemdisiran，在用以治疗成人全身性重症肌无力（gMG）的NIMBLE临床3期试验中达到主要终点。数据显示，每三个月皮下注射一次cemdisiran单药可平均抑制74%的补体活性，而与C5抗体pozelimab联用后，补体抑制率提升至近99%。同期，ASO疗法zilganersen也在亚历山大病（AxD）的关键试验中显著改善患者步行能力，成为首款在该疾病中显示出潜在疾病修饰作用的在研疗法。上述两款疗法预计将于2026年第一季度提交监管申请。 另一方面，用于治疗Dravet综合征的在研ASO疗法zorevunersen在为期三年的扩展研究中表现出持续的抗癫痫发作效果，并伴随认知与行为指标的持续改善，该疗法已在今年8月完成3期试验的首位患者给药。 在2025年三季度，FDA还向多款寡核苷酸疗法授予突破性疗法认定，适应症涵盖多种罕见疾病。其中包括适用于外显子44和51跳跃的杜氏肌营养不良症（DMD）的抗体-寡核苷酸偶联疗法del-zota与DYNE-251，以及用于天使综合征的ASO疗法apazunersen与ION582。 向更广泛适应症推进 寡核苷酸疗法的应用领域正从罕见病向常见疾病拓展。7月，FDA批准诺华（Novartis）的siRNA疗法Leqvio（inclisiran）扩展适应症，作为单药与饮食控制和运动联合使用，以降低成人高胆固醇血症患者的低密度脂蛋白胆固醇（LDL-C）水平。该药物每年仅需给药两次。此次标签更新是FDA基于该PCSK9靶向疗法降低LDL-C的积极数据主动发起。 在代谢性疾病领域，用于治疗代谢功能障碍相关脂肪性肝炎（MASH）的ASO疗法ION224也在三季度获得积极的2期结果：最高剂量组中有近60%的患者实现MASH疾病活动度改善，安慰剂组仅为19%。 同期，两款分别针对肥胖与阿尔茨海默病的siRNA疗法RN3161与ARO-MAPT于9月在澳大利亚和新西兰提交临床试验申请，标志着寡核苷酸疗法正向更广泛疾病领域推进。 在癌症领域也有多项进展。PD-1靶向siRNA疗法PH-762在皮肤癌1b期试验中，13例皮肤鳞状细胞癌（cSCC）患者中有6人在接受治疗后达到病理学完全缓解或接近完全缓解。另外，DNA癌症疫苗SCIB1与其改良版iSCIB1+在晚期不可切除黑色素瘤患者中展现亮眼疗效。临床2期试验结果显示，当两者与当前标准免疫检查点抑制剂联用时，疾病控制率（DCR）高达88.0%。 9月，两款分别针对肥胖与阿尔茨海默病的siRNA疗法RN3161与ARO-MAPT，也分别在澳洲与新西兰递交临床试验申请，意味着着寡核苷酸疗法正向更广泛适应症领域推进。 高额合作加码，彰显产业信心 三季度以来，寡核苷酸领域的商业研发合作也有诸多进展，多家企业通过高额合作加码siRNA领域布局。 9月，诺华接连达成两项大额siRNA疗法授权合作：其一，与Arrowhead Pharmaceuticals就后者开发的α-突触核蛋白靶向siRNA疗法ARO-SNCA达成总额高达20亿美元的合作。该疗法处于临床前阶段，拟开发治疗包括帕金森病在内的突触核蛋白病。其二，与Argo Biopharma就多项心血管siRNA管线达成合作，合作总额最高可达52亿美元，进一步夯实其在心血管代谢管线。 同时，Arrowhead Pharmaceuticals控股子公司维亚臻（Visirna Therapeutics）与赛诺菲达成最高2.65亿美元的合作：赛诺菲将获得siRNA疗法plozasiran（VSA001）在大中华区的开发与商业化独家权利。该疗法通过抑制载脂蛋白C-III（APOC3）的产生，用于治疗家族性乳糜微粒血症综合征及重度高甘油三酯血症。 此外，专注于开发RNA疗法的Arnatar Therapeutics宣布已于2024年完成5200万美元A轮融资。该公司专有的DARGER平台将siRNA沉默技术与基于ASO的基因上调技术相结合，开发具双重作用机制的RNA疗法，针对心脏代谢、肝、肾及中枢神经系统等疾病。 总而言之，2025年第三季度，寡核苷酸疗法在多个疾病领域持续取得突破，展现出从罕见病向更广泛疾病领域拓展的明确趋势。同时，产业涌现出的高额融资、合作等趋势，显示产业对这一领域的信心。 作为医药创新的赋能者，药明康德化学业务旗下专注于寡核苷酸和多肽及相关化学偶联药物的新分子业务平台——WuXi TIDES平台，围绕siRNA、ASO等寡核苷酸疗法，建立了化合物合成、工艺开发及生产的一站式服务平台，覆盖从药物发现、CMC开发，到商业化生产的全生命周期，加速将合作伙伴的创新构想转化为现实，更好地造福全球病患。以下案例将展示WuXi TIDES的一体化平台如何加速合作伙伴ASO药物的开发进程。 2023年，一家生物技术公司与WuXi TIDES合作进行ASO药物的早期筛选研究，WuXi TIDES的药物化学团队为其提供了超过400种携带骨架化学修饰的ASO化合物，以协助确定最具前景的分子。然而，早期研究发现，创新骨架修饰导致候选化合物中出现新的杂质。在最初的合成过程中，这些杂质占比高达25%，不仅降低了产率和纯化效率，还可能带来潜在毒性，给后续临床开发带来挑战。 面对这一难题，WuXi TIDES药物化学团队和工艺研发团队密切配合，从两个方向入手解决问题。一方面，药物化学团队与合作伙伴共同探索杂质产生的潜在原因，设计出定制化的amidite和分子砌块，规避杂质产生的关键合成机制，并快速生产这些新分子砌块，协助工艺研发团队加速验证工艺设计策略，以有效地控制杂质。此外，工艺研发团队通过优化工艺参数，系统性地降低了杂质的产生。最终，经过持续工艺优化，杂质占比成功从25%降低至5%，同时最终收率也从最初的0.5 g/mol提高到3.4 g/mol。 在该项目中，WuXi TIDES各团队高效协作，不仅在12个月内完成了先导化合物的优化、工艺开发及GMP生产，更帮助合作伙伴基于数据进行快速决策，选出综合效力、稳定性和开发潜力俱佳的ASO候选化合物，为后续临床研究奠定了坚实基础。随着越来越多的ASO以及其他寡核苷酸药物进入临床开发，这种产业协同模式将成为加快研发步伐的重要推动力。 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号回复“转载”，获取转载须知。