Novo Nordisk Research Center Gladsaxe ApS

诺和诺德和礼来无疑处于减肥症市场的顶端。今年第二季度，诺和诺德的Wegovy销售额为17亿美元，礼来的Zepbound销售额为12亿美元，这两家公司都赚取了丰厚的利润。在未来几年内，预计其还将继续主导肥胖症市场，而不会面临太大挑战。为了确保在竞争对手进入市场时保持领先地位，这两家公司正在斥资数十亿美元进行许可和并购交易。 根据Pitchbook 和Morning Star在9月9日发布的一份报告，这两家巨头可能会继续占据这一地位，直到竞争对手在2026年左右开始进入市场。但是，来自拓臻生物（Terns Pharmaceuticals）、硕迪生物（Structure Therapeutics）、辉瑞（Pfizer）和安进（Amgen）等公司的下一波药物看起来可能会击败目前的产品。据Pitchbook估计，到2031年，所有这些公司都可以联合起来争夺每年约2000亿美元的市场。 对此，礼来和诺和诺德并没有放任其不管，而是采取了一些行动。他们一直在收购公司并达成交易，以分散对肥胖症治疗的赌注。报告指出，这两家制药公司都非常有望在该领域进行进一步收购。两家公司还通过许可协议进行了小规模的尝试，以探索新的靶点或下一代GLP-1方法。 诺和诺德高管在3月份的投资者日演讲中表示，肥胖症是公司的主要投资重点。诺和诺德在业务开发方面最为高产，迄今为止，其拥有37个专注于心血管代谢疾病和肥胖症的合作伙伴关系。值得注意的是，该公司特别专注于寻找新的作用机制。 例如，诺和诺德正在大力投资多个治疗领域的siRNA技术，其中大部分是糖尿病和肥胖症。该公司还在建立蛋白质、肽和单克隆抗体的内部能力，同时通过合作和收购为其肥胖症产品线增加小分子选择。 与此同时，礼来在上半年为业务发展总共分配了14亿美元，包括里程碑付款、已完成的收购和股权投资。另外还投入了44亿美元用于研发；该公司有11种针对肥胖症的新分子正在开发中，其中包括1个强大的后期项目和9个正在进行的试验。 “在肥胖症领域，我们的战略是全面解决这场全球公共卫生危机，寻求针对各种合理的机制、适应症和剂型的机会，”礼来首席执行官David Ricks在8月初的公司第二季度财报电话会议上表示。 下面分别盘点了近年来诺和诺德和礼来为保持其在肥胖领域的领先地位而进行的交易。 诺和诺德 1、合作/交易方：Metaphore 日期：2024年5月9日 价值：6亿美元 资产：两种GLP-1受体激动剂 诺和诺德与Flagship Pioneering及该公司旗下子公司Metaphore Biotechnologies达成战略合作，共同开发至多两种下一代肥胖治疗药物。Metaphore将与Pioneering Medicines（Flagship 的内部药物开发部门）和 Novo Nordisk联合开展研发项目，Metaphore方负责产品的开发和临床前研究，诺和诺德则负责将这些项目推进至临床阶段。 本次合作重点是针对GLP-1受体开发多靶点长效药物，无需频繁给药即可达到减重目的。根据协议条款，诺和诺德将有望支付高达6亿美元的前期、开发和商业里程碑付款，以及许可产品年度净销售额的分级特许权使用费，这些费用将由Metaphore和Pioneering Medicines 分享；诺和诺德还将报销研发费用并参与Metaphore未来的融资。 据悉，这是诺和诺德与Flagship签订的第三份合作。早在2024年1月，诺和诺德已与Flagship孵化的Omega Therapeutics和Cellarity公司达成新药研究合作，开发用于肥胖管理的表观遗传药物和针对代谢相关脂肪性肝炎（MASH）的新型疗法，每项合作总额可能高达5.32亿美元。 2、合作/交易方：Catalent 日期：2024年2月5日 价值：165亿美元 资产：3个灌装-成品基地 2月5日，诺和诺德宣布公司已同意从诺和诺德的控股股东Novo Holdings收购3个灌装-成品基地，作为Novo Holdings同意通过165亿美元合并收购Catalent（康泰伦特）的交易的一部分。康泰伦特是一家总部位于美国新泽西州萨默塞特的全球合同开发和生产组织。根据协议条款，诺和诺德将以110亿美元的预付款收购这三个生产基地。 此次收购将在康泰伦特和Novo Holdings子公司合并后尽快完成，预计将在2024年底满足各种惯例成交条件后完成，包括康泰伦特股东和监管机构的批准。在收购完成之前，康泰伦特将继续独立运营，独立于Novo Holdings和Novo Nordisk。交易完成后，诺和诺德将履行诺和诺德正在收购的三个康泰伦特工厂的所有客户义务。此次收购灌装厂符合诺和诺德的战略，即让更多的糖尿病和肥胖症患者接受目前和未来的治疗。收购实现了生产规模和速度的扩张，同时为诺和诺德现有的供应网络提供了未来的选择性和灵活性。预计此次收购将从2026年起逐步提高诺和诺德的灌装能力。 3、合作/交易方：EraCal Therapeutics 日期：2024年1月24日 价值：2.55亿美元 资产：口服小分子项目 诺和诺德通过与瑞士生物技术公司EraCal Therapeutics签署的2.55亿美元的许可协议，增加了一种新的肥胖作用机制。该交易授予诺和诺德对EraCal 口服小分子计划的独家权利，该计划旨在控制食欲和体重以治疗肥胖症。 两家公司自2022年以来一直在合作，以寻找食物摄入调节和其他代谢表型的靶点。EraCals基于斑马鱼的技术平台源于苏黎世大学和哈佛大学的研究成果。它能够在一种完整的活生物体中大规模地分析像食物摄入这样的复杂表型。这种技术不但能够根据体内生物利用度和毒性对化合物进行筛选，还能够检测潜在候选药物在中枢神经系统中的不良反应，这些特征让它能够识别在体内更具特异性的化合物。 4、合作/交易方：Omega Therapeutics 日期：2024年1月5日 价值：5.32亿美元 资产：肥胖管理潜在新疗法 诺和诺德、Omega Therapeutics和Cellarity宣布，诺和诺德已分别与Flagship Pioneering旗下的这两家生物平台（bioplatform）公司达成研究合作，每项合作总额可能高达5.32亿美元。其中，诺和诺德与Omega的合作将利用Omega专有平台技术开发一种表观基因组控制器，旨在增强代谢活性，作为肥胖管理潜在新疗法；诺和诺德与Cellarity的合作则旨在解开代谢功能障碍相关脂肪性肝炎（MASH，原名为非酒精性脂肪性肝炎[NASH]）的新型生物驱动因子，并将利用Cellarity的平台开发针对该疾病的小分子疗法。 5、合作/交易方：Embark Biotech 日期：2023年8月30日 价值：5.12亿美元 资产：Embark Biotech，来自Embark Laboratories的资产 诺和诺德收购Embark Biotech，包括其先导代谢项目，以开发治疗肥胖和相关合并症的新型药物。交易金额可能超过4.7亿欧元（合5.12亿美元）。根据收购协议，诺和诺德将获得先导项目开发和商业化的全部权利，而Embark股东将获得1500万欧元预付款现金，并有资格获得高达5.12 亿美元的潜在开发、监管和商业里程碑付款。作为协议的一部分，诺和诺德还与Embark Laboratories进行了为期三年的研发合作。 6、合作/交易方：Inversago Pharma 日期：2023年8月10日 价值：10.75亿美元 资产：Inversago Pharma 诺和诺德收购Inversago pharma，囊获其用于治疗肥胖、糖尿病及其他代谢性疾病的临床阶段管线。根据协议，诺和诺德将支付6亿美元的预付款，如果里程碑达到，交易总额可高达10.75亿美元。据悉，Inversago致力于开发大麻素1型受体（CB1r）的反向激动剂，用于糖尿病肾病、肥胖、NASH、1型糖尿病等代谢性疾病。 7、合作/交易方：Flagship Pioneering 日期：2022年5月 价值：未披露 资产：多家公司合作相关研究项目 2022年5月，Flagship Pioneering和诺和诺德宣布合作创建一系列新颖的研究项目来进行药物开发转化。两家公司将探索应用Flagship创新生物平台，以应对心脏代谢和罕见疾病领域的科学挑战，并启动相关研究项目。 诺和诺德将为启动的研究项目提供资金，并拥有每个项目的独家许可选择权，目标则是在合作的前三年内启动三到五个研究项目。这种新颖的合作方式，为公司之间提供了广泛的创新机会，可以利用多家生物技术公司的技术平台，创建跨多个疾病领域的药物组合。 8、合作/交易方：Dicerna Pharmaceuticals 日期：2021年11月18日 价值：33亿美元 资产：Dicerna Pharmaceuticals 诺和诺德于2019年与Dicerna Pharmaceuticals合作寻找新的RNAi疗法，合作研究了30个肝细胞靶点，这些靶点可能在MASH、2型糖尿病、肥胖症和罕见病中产生新的疗法。诺和诺德对此感到满意，于2021年11月以约33亿美元的价格完全收购了该公司。除了肥胖之外，诺和诺德还看到了Dicerna的技术有可能找到治疗糖尿病、心血管疾病、MASH以及内分泌和出血性疾病的药物。 9、合作/交易方：Kallyope 日期：2018年6月21日、2024年9月 价值：未披露 资产：肥胖配体 这笔交易进展缓慢。诺和诺德和Kallyope最初于2018年6月达成了一项合作研究和期权协议，共同开发治疗肥胖症和糖尿病的新型多肽类药物。当时没有公布财务细节，但该交易涉及预付费用和研究支持。诺和诺德获得了最多六种产品的权利，并提供了许可费（如果有）。Kallyope正在探索肠脑轴，正在进行四个新陈代谢项目。 本月早些时候，有了一些关于该合作的进展情况。据悉，诺和诺德行使了许可Kallyope确定的用于肥胖的配体的选择权。同样，财务细节也处于保密状态。诺和诺德表示，其相信自己在Kallyope计划中发现了一种新的肥胖机制。现在，诺和诺德将接管临床前和临床开发、制造和商业化。Kallyope已收到预付款，并且可能会在开发和销售里程碑以及特许权使用费方面收到额外付款。 礼来 1、合作/交易方：Haya Therapeutics 日期：2024年9月5日 价值：高达10亿美元 资产：RNA靶向疗法 今年9月，礼来与Haya Therapeutics宣布达成一项总额高达10亿美元的多年协议。两家公司将应用HAYA的RNA引导基因调控平台来支持肥胖和相关代谢疾病的临床前药物研发工作。两者将确定多个能够调控基因表达的RNA药物靶点，以治疗这些慢性疾病。 Therapeutics是一家精准医疗公司，致力于开发可编程疗法，靶向不编码蛋白的调节性RNA，以重新编程包括心血管疾病、代谢疾病和癌症在内多种疾病的病理细胞状态。该公司正在利用其创新平台获得有关疾病细胞状态生物学和相关长链非编码RNA（lncRNA）的新见解。HAYA的主打项目是HTX-001，正在开发用于治疗心力衰竭。HAYA还在开发一系列靶向lncRNA的精准疗法，用于针对其他组织疾病的细胞特异性治疗。 HAYA专有的基因调控发现平台能够识别组织、疾病和细胞特异性的lncRNA靶标，并开发相对应的RNA靶向疗法，从而重新编程细胞并潜在使之恢复成健康状态。与现有疗法相比，这类疗法可能更有效且毒性更小。此次合作将利用HAYA的基因调控平台来识别、检视和验证多个创新lncRNA靶标，旨在开发出治疗肥胖症和相关代谢疾病的新疗法。 2、合作/交易方：BioAge 日期：2023年10月 价值：未披露 资产：azelaprag与Zepbound的组合疗法 礼来与BioAge同意携手开展一项临床试验，将后者的apelin受体APJ激动剂azelaprag与礼来的Zepbound进行组合。该临床试验的期望是这种组合能够提升礼来这款重磅炸弹级产品的减肥潜力。 该临床试验供应协议一直都在进行，但礼来是通过其独立的临床开发组织Chorus来进行这项研究的。该部门与生物技术公司合作，通过临床概念验证来开发资产。 礼来还进一步加大了参与力度，于2月参与了BioAge的D轮融资。BioAge筹集了1.7亿美元，投资方包括RA Capital、Cormorant、SV Health、礼来和安进。根据9月18日美国证券交易委员会（SEC）提交的文件显示，这家生物技术公司提交了上市申请，并寻求高达1.533亿美元的融资。 3、合作/交易方：Versanis Bio 日期：2023年7月14日 价值：19.25亿美元 资产：Versanis Bio 2023年7月，礼来公司宣布以19.25亿美元收购Versanis Bio，这是一家专注于开发治疗心脏代谢疾病新药的私人临床阶段生物制药公司。交易的核心是bimagrumab，这是一种单克隆抗体，旨在在不影响肌肉质量的情况下减少脂肪。诺华开发了治疗肌肉疾病的疗法，但研究未能显示患者身体机能的改善。然而，研究人员确实注意到，服用这种药物的人体重减轻了。 快进到席卷制药行业的减肥热潮，礼来通过近20亿美元的支出从诺华的抛售中脱颖而出。Bimagrumab正在针对成人的IIb期BELIEVE研究中进行测试，以实现和保持减脂和健康的身体成分。据ClinicalTrials.gov称，预计该试验将于2025年年中完工。 参考资料： [1]Lilly and Novo Spend Billions to Expand Obesity Pipelines Beyond GLP-1s.September 25, 2024.Biospace. [2]165亿美元！诺和诺德收购Catalent.医药魔方Pro.2024年02月05日. [3]速递 | 2.35亿欧元！诺和诺德囊获口服小分子减肥药.药明康德.2024年01月24日. [4]速递 | 开发肥胖、NASH创新疗法，诺和诺德/ Flagship达超10亿美元合作！.药明康德.2024年01月05日. [5]再拿一城！诺和诺德5.12 亿美元收购减肥新秀Embark Biotech.药智头条.2023年09月01日. [6]【深度解析】诺和诺德超10亿美元收购Inversago，和礼来比眼光如何？.萝卜药闻.2023年08月14日. [7]超43亿！诺和诺德出手下一代减肥疗法.动脉新医药.2024年05月11日. [8]最新布局！礼来达成10亿美元合作开发RNA靶向疗法.药明康德.2024年09月05日. 为促进抗体行业的交流与创新，2024年10月16-17日第七届金秋十月抗体产业发展大会如约而至。会议旨在为研究人员提供一个互动交流的平台，有助于推动抗体产业的进一步发展。 会议内容 时间：2024年10月16-17日 地点：上海张江（酒店定向通知） 规模：600-800人 主办单位：生物制品圈、抗体圈 演讲支持：Entegris、瑞孚迪、AS ONE CORPORATION 会议费用：免费FREE!（仅收取100元报名定金，含参会学习、茶歇、会议手册，定金概不退还），先到先得，报完即止！ 报名方式：扫描下方二维码或点击文章最底部“阅读原文”→ 填写表格 → 报名成功（报名志愿者，承担一定工作，请慎重考虑，免交定金）！ 组委会获得报名信息后，根据报名信息进行初筛，并进一步与报名者沟通确认，实现精准邀请。最终有机会进入大会微信群（严格审核通过）。 日程安排 更多嘉宾正在邀请中 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

Novo and Lilly/Taylor Tieden for BioSpace Novo Nordisk and Eli Lilly are expected to rule the obesity market for a few more years without much challenge. To ensure they stay there as competition enters, the companies are spending billions in licensing and M&A deals. Novo Nordisk and Eli Lilly are undoubtedly at the top of the weight loss market. With $1.7 billion in second-quarter sales recorded for Novo’s Wegovy and $1.2 billion for Lilly’s Zepbound, the companies are raking in profits. The two behemoths are likely to remain in that spot until competitors begin to arrive on the market around 2026, according to a report from Pitchbook and Morning Star issued on September 9. But the next wave of drugs, coming from companies like Terns Pharmaceuticals, Structure Therapeutics, Pfizer and Amgen, look like they could beat the current offerings. All these companies could come together to battle for a market Pitchbook estimates could reach $200 billion annually by 2031. But Lilly and Novo are not standing idly by. They’ve been scooping up companies and making deals, diversifying their bets on obesity treatments. And both pharmas are highly anticipated to make further acquisitions in the space, according to the report. Both have also taken smaller bites with licensing deals to explore new targets or next-generation GLP-1 approaches. Obesity is a key investment focus for Novo, executives said during an investor day presentation in March. Of the two, Novo has been the most prolific on the business development stage by far, with 37 partnerships focused on cardiometabolic diseases and obesity, according to the presentations. The company is specifically focused on finding new mechanisms of action. For example, Novo is heavily investing in siRNA technology for a number of therapy areas, the majority of which are in diabetes and obesity. The company is also building out internal capabilities in proteins, peptides and monoclonal antibodies, while partnerships and acquisitions are adding small molecule options to its obesity pipeline. Meanwhile, Lilly allocated $1.4 billion for business development overall, including milestones, closed acquisitions and equity investments in the first half of the year. Another $4.4 billion went to total R&D; the pharma has 11 new molecules in development for obesity, including a robust late-stage program and nine trials currently running. “In obesity, our strategy is to comprehensively address this global public health crisis, pursuing opportunities against every rational mechanism, indication, and dosage form,” said CEO David Ricks on the company’s second quarter earnings call in early August. Read on for more on the deals that Novo and Lilly hope will keep them at the top of the obesity world. Lilly: Haya Therapeutics Partnership Date: September Value: Up to $1 billion Asset(s): Multiple RNA targets Most recently, Lilly put up to $1 billion on the line —although the exact financial breakdown was not disclosed—to work with Haya Therapeutics earlier this month. The Swiss biotech is using an RNA-guided genome platform to target obesity and other metabolic conditions. Haya will conduct drug discovery to find multiple tissue-, disease- and cell-specific long non-coding RNA targets (lncRNA) to develop into therapeutics. Specifically, Lilly is looking for treatments with better efficacy and less toxicity than existing options for weight loss. That’s, of course, the holy grail. While Wegovy and Zepbound are undeniably effective, they are associated with gastrointestinal side effects and muscle loss. The next generation of therapies will seek to imnprove on those two measures, but also on delivery. Novo: Metaphore Partnership Date: May Value: $600 million Asset(s): Two GLP-1 receptor agonists Novo has worked with venture creation firm Flagship Pioneering since 2022 (see below), but in May, they doubled down. The Danish pharma signed a deal with one of Flagship’s portfolio companies, Metaphore Biotechnologies, to develop two next-generation GLP-1 receptor agonists. The deal included up to $600 million in upfront, development and milestone payments. Novo plans to use Metaphore’s MIMIC platform, which can copy the interactions between molecules to develop therapeutics to activate the GLP-1 receptor and related pathways. The deal also includes “a novel machine learning approach to obesity management,” the companies said in announcing the deal. Novo: Catalent Acquisition Date: February Value: $16.5 billion Asset(s): Three fill finish sites This list would not be complete without this outlier, Novo Holdings’ $16.5 billion acquisition of contract development and manufacturing organization Catalent. This deal does not bolster Novo’s pipeline, exactly, but will certainly support the company’s obesity-driven revenue. Novo Nordisk’s holding company took control of three of Catalent’s manufacturing sites to bolster production of the blockbuster drugs Ozempic for diabetes and Wegovy for weight loss. Both use the same active ingredient, semaglutide. The troubled manufacturer had revenue losses of $539 million in 2023 as demand for COVID-19 vaccines and treatments waned, plus debt of more than $5 billion. The company had also faced multiple quality control concerns. Novo: EraCal Licensing Deal Date: January Value: $255 million Asset(s): Oral small molecule program Sometimes, you have to dig a little deeper into existing partnerships. Novo did exactly that, adding on a new mechanism of action in obesity through a $255 million licensing deal with Swiss biotech EraCal Therapeutics signed in January. The deal granted Novo exclusive rights to EraCal’s oral small molecule program, which aims to control appetite and body weight to treat obesity. The two companies had been working together since 2022, when they entered into a collaboration to find targets for food intake regulation and other metabolic phenotypes. The partnership examined zebrafish larvae to find new targets to act against obesity. Novo: Omega Therapeutics Licensing Deal Date: January Value: $532 million Asset(s): Epigenomic controller program Novo inked the first of two licensing options in obesity this year with Flagship in January, starting with Omega Therapeutics . The pharma opted in on a program designing an epigenomic controller designed to enhance metabolic activity, with the hope of developing a new treatment for obesity management. The agreement also included a second opt-in for a metabolic dysfunction-associated steatohepatitis (MASH) therapy with Flagship’s Cellarity. Flagship’s Pioneering Medicines and Novo will jointly support the programs through preclinical work and then Novo will advance them into the clinic and reimburse R&D costs. Novo pledged $532 million upfront for each agreement in upfront, development and commercial milestone payments. Lilly: Fauna Partnership Date: December 2023 Value: $494 million Asset(s): Multiple weight loss targets Lilly looked to the animal kingdom for some new weight loss targets in a deal signed with Fauna Bio worth up to $494 million in December 2023. The multi-year partnership will see the two work on finding new targets for weight loss drugs using Fauna’s artificial intelligence platform called Convergence. The platform analyzes genomic data from 452 animal species and tissues along with human data to find novel drug targets. Lilly: BioAge Trial Partnership Date: October 2023 Value: Not disclosed Asset(s): Azelaprag Lilly’s partnership with BioAge stands out a bit on this list. The companies agreed to work together on a clinical trial pairing the biotech’s apelin receptor APJ agonist azelaprag with Lilly’s Zepbound. The hope with thethis clinical trial is that the combo will boost the weight loss potential of Lilly’s mega-blockbuster. These kinds of clinical trial supply agreements happen all the time, but Lilly is conducting the research through its independent clinical development organization called Chorus. The unit works with biotechs to develop assets through clinical proof of concept. Lilly put more skin in the game by also participating in BioAge’s series D financing in February. BioAge raised $170 million with backing from RA Capital, Cormorant, SV Health, Lilly and Amgen. The biotech has since filed to go public and is seeking up to $153.3 million, according to a September 18 SEC filing . Novo: Embark Biotech Acquisition Date: August 2023 Value: $507 million Asset(s): Embark Biotech, assets from Embark Laboratories Novo did a double deal with Embark Laboratories in August 2023, fully acquiring Embark Biotech and signing a three-year research collaboration with the lab. In Embark Biotech, Novo scored a metabolic program for up to $507 million. And for the research collaboration, Novo gained an option to acquire selected assets retained by Embark Laboratories based on Embark Biotech discoveries in obesity, type 2 diabetes and other indications. Novo: Inversago Pharma Acquisition Date: August 2023 Value: $1.1 billion Asset(s): Inversago Pharma Novo is already seeing the fruits of its $1.1 billion buyout of Inversago Pharma , a Canadian company that had been developing novel cannabinoid receptor 1 (CB1) receptor-based therapies. The August 2023 deal brought in a new modality for Novo to explore in its ever-expanding obesity pipeline. Just last week, the company revealed the first results for one of the candidates, monlunabant, showing that the oral CB1 inverse agonist cut weight by 15 lbs after 16 weeks. The data reveal was low on detail, however, and Novo did not present the weight loss as a percentage of bodyweight, which has been common in these types of trials. Novo also noted some “mild to moderate neuropsychiatric side effects,” such as anxiety, irritability and sleep disturbances. This class of drugs has been known to cause neuropsychiatric issues, including suicidality, so Novo said it intends to work with the dosing in future trials, after proving that monlunabant can in fact reduce weight. Lilly: Versanis Bio Acquisition Date: July 2023 Value: $1.925 billion Asset(s): Versanis Bio In July 2023 , Lilly swept in and bought out Versanis , a biotech that had formed around a Novartis castoff, for $1.925 billion. At the center of the deal is bimagrumab , a monoclonal antibody that aims to reduce fat without affecting muscle mass. Novartis developed the therapy in muscle disorders but studies failed to show improvement in patients’physical function. Researchers did, however, note that people taking the drug lost weight. Fast-forward to the weight loss craze that is sweeping the pharmaceutical industry, and Lilly jumped on Novartis’ discard through the nearly $2 billion outlay. Bimagrumab is being tested in the Phase IIb BELIEVE study for adults to achieve and maintain fat loss and a healthy body composition. Completion is expected in mid-2025, according to ClinicalTrials.gov . Novo: Flagship Partnership Date: May 2022 Value: Not disclosed Asset(s): Multiple company partnerships Why work with one company when you could work with 41? That’s what Novo did in signing a partnership with prolific biotech creator Flagship Pioneering in May 2022. The deal focused on cardiometabolic and rare diseases, providing Novo with access to the platforms developed by Flagship’s many companies. Novo offered funding for initiated research programs and will have an exclusive option on any programs licensed from the deal. The goal was to kickstart three to five programs within the first three years. The deal has since produced collaborations with Metaphore and Omega in obesity (see above), plus Cellarity in MASH. Novo: Dicerna Acquisition Date: December 2021 Value: $3.3 billion Asset(s): Dicerna Novo tapped into Dicerna Pharmaceuticals in 2019 to find new RNAi therapies, in a partnership that examined 30 liver cell targets that could yield new therapeutics in MASH, type 2 diabetes, obesity and rare diseases.  Satisfied with the work, Novo went all in, buying out the company entirely in November 2021 for about $3.3 billion. The first target from the original collaboration, a NASH drug, entered the clinic in 2022, but Novo was also looking to the deal to expand the company’s RNAi research. Besides obesity, Novo sees the possibility for Dicerna’s technology to find therapies for diabetes, cardiovascular disease, MASH and endocrine and bleeding disorders. Novo: Kallyope Licensing Deal Date: June 2018, September 2024 Value: Not disclosed Asset(s): Ligand for obesity This deal has a slow burn. Originally signed in June 2018 , Novo and Kallyope agreed to discover novel peptides for obesity and diabetes. No financial details were released at the time, but the deal involved an upfront fee and research support. Novo gained the rights to up to six products and offered a licensing fee if any were optioned. Kallyope is exploring the gut-brain axis, with four programs underway for metabolism. Earlier this month, we finally heard how the partnership was going . Novo exercised an option to license a ligand identified by Kallyope for obesity. Again, financial details were kept under wraps. Novo said it believes it’s found a new mechanism for obesity in the Kallyope program. Now, the Danish pharma will take over preclinical and clinical development, manufacturing and commercialization. Kallyope has received an upfront option payment and may receive additional payments down the line in development and sales milestones and royalties.

2024上半年，诺和诺德实现营收1334亿丹麦克朗，同比增长24%，业绩保持增长。 司美格鲁肽的放量是业绩增长的关键因素。司美格鲁肽降糖注射剂Ozempic实现营收567亿丹麦克朗，司美格鲁肽降糖口服剂Rybelsus营收109亿丹麦克朗，司美格鲁肽减重注射剂Wegovy营收210亿丹麦克朗，司美格鲁肽合计销售额887亿丹麦克朗，同比增长43%，占诺和诺德总营收的2/3。 在司美格鲁肽全球热卖的同时，诺和诺德也正在不断调整优化自身的研发策略和业务布局，通过丰富产品组合，进一步加强降糖减脂领域的霸主地位，同时，也在逐渐延伸慢病治疗边界。 关注新生力量 根据诺和诺德2024年中报显示，诺和诺德在企业战略发展方面，将糖尿病和肥胖业务作为关键优先研发领域，主要的战略举措则是进一步丰富相关治疗领域的产品组合，布局将更加广泛和深入。 在减重领域，凭借Wegovy打开了肥胖症的市场。未来，诺和诺德将通过重点建立差异化的产品组合，从单纯的减重拓展到针对肥胖症患者的健康状况管理。除Wegovy外，复方制剂CagriSema已启动全球III期临床试验，两款全新的减重药物GLP-1R/胰淀素受体双靶点激动剂Amycretin、口服小分子CB1R反向激动剂Monlunabant的减重疗效也备受期待。 CagriSema是一款复方制剂，它包含2.4mg长效胰淀素受体类似物卡格列肽（Cagrilintide）和2.4mg长效GLP-1RA司美格鲁肽。CagriSema的II期临床数据显示，在治疗的32周，CagriSema治疗组体重下降15.6%，减重效果优于单独使用卡格列肽和司美格鲁肽。53.6%的CagriSema组受试者体重降幅超过15%。 目前，CagriSema已启动全球III期临床，主要针对超重/肥胖症适应症。另外，针对伴有超重/肥胖的2型糖尿病适应症的全球III期临床、伴有心血管疾病的肥胖人群的全球III期临床也正在进行。 诺和诺德Amycretin共开发了口服和皮下注射两种剂型。诺和诺德在今年的CMD会议上公布了口服Amycretin的初步I期临床数据：接受每日口服1次Amycretin治疗的患者，在治疗的第12周，体重较基线下降13.1%，对比安慰剂组受试者的体重降幅仅1.1%。目前，口服Amycretin已完成I期临床试验，皮下注射剂型Amycretin的I期临床试验数据预计将在2025年读出。 另一款新药Monlunabant（INV-202）是一种CB1反向激动剂，CB1是一种大麻素受体，在调节食欲和心脏代谢中发挥重要作用。2023年8月，诺和诺德以10.57亿美元收购加拿大公司Inversago Pharma，由此，诺和诺德获得该公司的主要资产Monlunabant。 Monlunabant的I期临床数据显示，在治疗的第28天，Monlunabant组平均体重下降3.3%（即3.5KG），安慰剂组体重增长0.5%（即0.6KG）。Monlunabant治疗肥胖症和糖尿病肾病的II期临床试验正在进行。 在降糖领域，目前诺和诺德的产品组合已覆盖胰岛素、注射型和口服型GLP-1药物。未来，诺和诺德将通过持续推进在研管线，将糖尿病的创新疗法扩展至糖尿病共患病中，例如糖尿病肾病等，以解决糖尿病管理中的尚未满足需求。 延伸慢病治疗边界 借助GLP-1产品的开发，诺和诺德的研发布局正在不断拓宽边界，朝着更广阔的慢病领域进发。 根据券商研究资料显示，截至2023年底，司美格鲁肽全球共涉及148项临床试验，除了糖尿病和肥胖症适应症以外，在NASH、疼痛、慢性肾病、卒中等方面均有布局。其中，司美格鲁肽治疗NASH的Ⅱ期临床试验已取得积极疗效数据，目前正在进行全球III期临床试验。另外，司美格鲁肽在治疗射血分数保留型心力衰竭肥胖成人患者的III期临床试验中同样取得了积极的疗效结果。 值得一提的是，GLP-1的另一巨头礼来，同样在扩展替尔泊肽的应用领域。根据礼来2024年中报资料，礼来已向FDA和EMA提交替尔泊肽用于治疗中度至重度阻塞性睡眠呼吸暂停的上市申请，预计FDA方面最早于2024年底给出相关回复。 此外，礼来正在就替尔泊肽用于治疗代谢功能障碍相关的脂肪性肝炎的III期临床试验注册策略与有关监管机构进行洽谈。 进军更广阔的心血管领域 相较于其他跨国药企通过积极投资并购拓展业务领域，诺和诺德的并购活动则更为谨慎。2010年—2023年，诺和诺德仅进行过14项并购，在研发出GLP-1减重，心衰等适应症前，糖尿病是诺和诺德的核心，研发管线的高度专注是诺和诺德谨慎并购的核心原因。 但是，自2020年开始，诺和诺德的并购步伐不断加快。尤其是2023年，6月-10月期间相继宣布5项并购项目，交易金额合计高达35亿美元。其中，收购Inversago Pharma公司和Embark Biotech是为了进一步强化肥胖领域的布局，在加码减重领域外，KBP Biosciences（2023）、Prothena（2021）、Corvidia Therapeutics（2020）的三项并购则强化了心血管疾病领域的研发能力。 2023年10月，诺和诺德以13亿美元从KBP Biosciences公司获得用于治疗心血管和肾脏疾病的高血压控制药物Ocedurenone，以加强自身心血管领域布局。Ocedurenone是一款口服小分子非甾体盐皮质激素受体拮抗剂，目前，正在开展用于治疗未得到控制的高血压合并晚期慢性肾病的III期临床试验，预计将在2024年9月完成。 此前，Ocedurenone的Ⅱ期临床试验数据显示，在12周随机试验中，Ocedurenone能够使受试者的收缩压明显下降。此外，Ocedurenone的安全性高，高钾血症风险低于1%，并且无类固醇副作用。 2021年，诺和诺德以12亿美元收购Prothena公司，获得抗淀粉样蛋白免疫药物PRX004及其转甲状腺素蛋白淀粉样变性（ATTR）项目，目前ATTR项目正处于临床II期临床试验中。 2020年，诺和诺德以最高21亿美元收购Corvidia Therapeutics公司，获得IL-6单抗Ziltivekimab，通过阻断IL-6通路降低炎症，从而降低ASCVD和CKD患者的主要心血管不良事件风险，目前正在开展III期临床试验。 这些正在孕育中的产品管线，如同未来业绩增长的“蓄水池”，随着日后的逐一兑现，还将为诺和诺德源源不断地贡献营收，成为新的重要增长点。核心产品放量增长，内生+外延并举，持续迎来研发进展，诺和诺德未来可期。 参考资料： 1.诺和诺德历年业绩报告 2.诺和诺德2023年ADA会议报告 3.诺和诺德2024年资本市场日报告 4.礼来2024年中报 5.《从并购看诺和诺德业务布局思路》，华创证券 声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。 责任编辑 | 史密斯 转载开白 | 马老师 18996384680（同微信） 商务合作 | 王存星 19922864877（同微信）  阅读原文，是受欢迎的文章哦