PROMETHERA Biosciences SA

The global stem cell therapy market was valued at $10–12 billion in 2022 and is projected to grow at a compound annual growth rate (CAGR) of 10–15%, potentially surpassing $31.41 billion by 2030. The application prospects for stem cell therapies can be categorized into three main areas: off-the-shelf cell therapies, regenerative medicine, and gene therapy vehicles. Among the 25 approved stem cell therapies worldwide, mesenchymal stem cell (MSC) therapies and hematopoietic stem cell (HSC) therapies constitute 76% of the total, reflecting their advanced technological maturity. Global Transactions of Stem Cell Therapy in Patsnap SynapseMechanisms of Stem Cell TherapyThe mechanisms of stem cell therapy revolve around their core properties of self-renewal and multi-lineage differentiation, which grant them significant value in regenerative medicine and tissue repair. Self-renewal refers to the ability of stem cells to proliferate indefinitely without differentiation, maintaining their undifferentiated state. Through mitosis, stem cells produce progeny that preserve stem cell quantity and functionality. This process is regulated by multiple signaling pathways, including the transcription factors Oct4, Sox2, and Nanog in embryonic stem cells, while adult stem cells rely primarily on the p16-Rb and p19-p53 signaling pathways. Clinical Trials for Cell Therapies Using PSCs1Multi-lineage differentiation allows stem cells to transform into various cell types, such as neurons, cardiomyocytes, and osteocytes, under specific conditions. This differentiation process is influenced by microenvironmental factors and signaling pathways like Wnt, Notch, BMP, and Hedgehog. By introducing specific growth factors and chemical agents, scientists can precisely guide stem cell differentiation into desired cell types for treating diseases such as osteoarthritis, spinal cord injuries, myocardial infarction, and neurological disorders. Main Targets of Stem Cell Therapy Applications in Patsnap SynapseStem cells also exhibit remarkable immunomodulatory and anti-inflammatory effects, helping to suppress abnormal immune responses and restore immune system balance. MSCs, in particular, have been widely studied and proven effective in these areas. MSCs regulate immune cell function through direct cell-to-cell contact and secretion of effector molecules such as growth factors, cytokines, and chemokines. For instance, MSCs can inhibit T-cell activation and proliferation while promoting the activity of regulatory T cells (Tregs), thereby alleviating inflammation. Additionally, MSCs secrete anti-inflammatory factors like transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10), which reduce inflammatory mediators, alleviate symptoms, and protect tissues from further damage. The stem cell hierarchy2The paracrine effects of stem cells involve the secretion of various bioactive molecules such as cytokines, growth factors, chemokines, microRNAs, and extracellular vesicles, which participate in intercellular communication, tissue repair, and regeneration. These molecules play crucial roles in diverse physiological and pathological processes. For example, growth factors secreted by stem cells, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), promote angiogenesis, accelerate wound healing, and facilitate tissue repair. Anti-inflammatory cytokines such as interleukin-6 (IL-6), IL-10, and TGF-β help regulate immune cell function, suppress inflammation, and support tissue repair. For instance, IL-10 reduces the production of inflammatory mediators, mitigating inflammation and protecting tissues from further damage. Layers of complexity in stem cell systems2Stem cells possess homing ability, a critical biological characteristic that enables them to migrate toward injured or inflamed sites in the body. Damaged tissues release bioactive factors that bind to receptors on the surface of stem cells, directing them to the injury site. For example, damaged tissues secrete stromal cell-derived factor-1 (SDF-1), which interacts with the CXCR4 receptor on stem cells, guiding their migration. Additionally, growth factors, adhesion molecules, and inflammatory factors released at the injury site further enhance stem cell migration and homing. The homing process encompasses not only migration but also the differentiation of stem cells into necessary cell types within the specific microenvironment of the injury, contributing to tissue repair and regeneration. Stem cell therapy design2Stem cells can differentiate into various types of tissue cells, aiding the regeneration and repair of damaged or dysfunctional tissues. Whether addressing skin wounds, myocardial injury, or neurodegenerative diseases, stem cell therapy provides new cellular sources for damaged tissues, promoting recovery and functional reconstruction. For instance, mesenchymal stem cells (MSCs) can differentiate into bone, cartilage, and adipose cells, making them suitable for treating conditions like osteoarthritis and spinal cord injuries. Their multi-lineage differentiation potential allows stem cells to transform into cell types needed by injured tissues under specific conditions, replacing damaged or dead cells and restoring tissue function. For example, following myocardial infarction, MSCs can differentiate into cardiomyocytes, replacing damaged myocardial cells and improving cardiac function. This cell replacement capability not only offers a new source of cells but also facilitates structural and functional recovery of damaged tissues. Another critical mechanism is microenvironment regulation. Stem cells secrete various growth factors and cytokines to modulate the microenvironment of injured tissues, promoting cell proliferation and tissue repair. For example, hepatocyte growth factor (HGF) secreted by stem cells supports liver cell regeneration and improves liver function. Additionally, vascular endothelial growth factor (VEGF) promotes angiogenesis, improving blood supply to damaged tissues and accelerating the repair process. Development of the induced pluripotent stem cell (iPSC) technology3Stem cells can also secrete anti-apoptotic factors that prevent cell death, which is crucial for protecting damaged tissues and maintaining tissue homeostasis. By inhibiting apoptosis, stem cell therapy enhances tissue survival and repair, improving therapeutic outcomes. Anti-apoptotic factors such as Bcl-2 and Bcl-xL inhibit apoptotic signaling pathways, protecting cells from damage. For instance, Bcl-2 prevents apoptosis by inhibiting the release of cytochrome c from mitochondria, thereby protecting cells in damaged tissues. This anti-apoptotic effect helps maintain tissue integrity and functionality, reducing cell loss. Additionally, stem cells secrete antioxidants and anti-inflammatory factors, shielding cells from oxidative stress and inflammatory damage, and preserving cell survival and function. Major Diseases Targeted by Stem Cell Therapy in Patsnap SynapseRegional R&D Characteristics of Stem Cell TherapyAs a regenerative medicine technique, stem cell therapy uses stem cells or their derivatives to stimulate the body's healing processes and repair damaged, diseased, or injured tissues, representing a promising frontier in transplantation. Key Development Regions for Stem Cell Research in Patsnap SynapseThe United States leads stem cell research and application, supported by a robust scientific foundation and a comprehensive regulatory framework. Hematopoietic stem cell transplantation for hematologic diseases was among the earliest stem cell technologies adopted clinically and remains the only globally recognized stem cell therapy. U.S. research institutions and companies, such as the Mayo Clinic, have made significant advances, exploring stem cell treatments for neurodegenerative diseases, cardiac conditions, and diabetes. Europe is also at the forefront, with countries like Germany, the UK, and France making notable contributions through institutions and companies like BioTime and STEMCELL Technologies. Germany's Max Planck Institute and the University of Cambridge in the UK have achieved significant breakthroughs in both fundamental and clinical applications of stem cells. European firms like TiGenix and Promethera Biosciences have conducted extensive clinical trials on stem cell therapies for liver and cardiovascular diseases. Clinical Research Directions and Targets of Stem Cell Research in Patsnap SynapseChina has made remarkable progress in stem cell research and applications, fostered by governmental support and favorable policies. Institutions like Peking University and companies affiliated with East Hospital have achieved notable outcomes. Japan, led by Kyoto University and the University of Tokyo, has also made significant advances, with Shinya Yamanaka receiving a Nobel Prize for discovering induced pluripotent stem cells (iPSCs). South Korean firms such as Celltrion and GC Pharma have conducted extensive trials on stem cell therapies for autoimmune and neurodegenerative diseases. Indian companies, like Stempeutics Research, have also made strides in treating osteoarthritis and spinal cord injuries using stem cell therapies. Main R&D Institutions for iPSC Drugs in Patsnap SynapseGlobal Competitive Landscape of Stem Cell TherapyFate Therapeutics is a leading biopharmaceutical company specializing in regenerative medicine and immunotherapy, focusing on developing immune cell therapies based on induced pluripotent stem cells (iPSCs). Utilizing its proprietary iPSC technology platform, the company generates and expands NK and T cells with specific biological properties for treating cancer and other immune-related diseases. Key products include iPSC-derived NK cells (such as FT500, FT516, FT538, and FT596) and T cells (such as FT819), which have demonstrated good safety profiles and preliminary efficacy in various clinical trials. For example, in a Phase 1 clinical trial for relapsed/refractory B-cell lymphoma, FT516 achieved complete remission in six out of eight patients. Fate Therapeutics has a strong foundation in iPSC technology, a broad patent portfolio, and collaborations with major pharmaceutical companies, accelerating its product development and commercialization. Its robust manufacturing capabilities and extensive clinical data position it as a leader in stem cell drug research. Mesoblast Limited is a biopharmaceutical company dedicated to developing allogeneic mesenchymal precursor cell (MPC)-based therapeutic products, focusing on cardiovascular, orthopedic, and immune diseases. Its flagship product, Remestemcel-L, has been approved in Japan for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) and has shown promising results in clinical trials for chronic heart failure and acute respiratory distress syndrome (ARDS). Another key product, Rexlemestrocel-L, has exhibited significant efficacy in Phase 3 trials for chronic heart failure and chronic low back pain. With its proprietary MPC technology platform and extensive clinical experience, Mesoblast has amassed substantial clinical data in the cardiovascular and orthopedic fields, showcasing its strong competitive edge. The company’s partnerships with global pharmaceutical firms have further accelerated its product development and commercialization. Product Pipeline of Mesoblast Limited in Patsnap SynapseAthersys, Inc. is a biotechnology company focused on regenerative medicine, primarily developing MultiStem® cell therapy based on multipotent adult progenitor cells (MAPCs). This therapy has shown broad therapeutic potential and positive clinical results for diseases such as stroke, traumatic brain injury, and ARDS. MultiStem® has received FDA Fast Track and RMAT designations, expediting its development and approval processes. Leveraging its proprietary technology platform and rich clinical experience, Athersys collaborates with international partners to advance the clinical research and commercialization of its products, offering new treatment options for patients with various diseases. BlueRock Therapeutics focuses on cell therapies using iPSC technology, targeting neurodegenerative and cardiovascular diseases. Its core product, bemdaneprocel (BRT-DA01), an iPSC-derived dopaminergic neuron therapy for Parkinson’s disease, has received FDA Fast Track designation and demonstrated good safety and cell survival in Phase 1 clinical trials. BlueRock benefits from its close collaboration with Bayer, which provides strong R&D and financial support, positioning it as a leader in the cell therapy field. TiGenix NV (acquired by Takeda) focuses on gastrointestinal and cardiovascular diseases, with its primary product, Cx601 (allogeneic adipose-derived stem cells), approved in the EU as the first stem cell therapy for complex perianal fistulas. Promethera Biosciences specializes in liver diseases, with its main product, HepaStem® (allogeneic liver stem cells), targeting acute liver failure and supported by unique technology and multiple clinical trials. Cellular Biomedicine Group (CBMG) focuses on cancer immunotherapy and autoimmune diseases, leveraging its experience with CAR-T and mesenchymal stem cell therapies, with several products in clinical trial stages. In China, significant progress has been made in the stem cell drug field. EdiGene focuses on gene editing and stem cell therapy, with its edited hematopoietic stem cell product ET-01 approved for clinical trials, showcasing deep expertise in gene editing technology. BGI Shenzhen excels in genomics and stem cell research, offering personalized and precision medicine solutions widely applied in genetic disease diagnosis and cancer screening. Vcanbio dominates China’s cell storage market, providing high-quality cell storage services and stem cell therapy products, with several stem cell products, such as dental pulp stem cell injections and Inaticabtagene Autoleucel cell injections, entering clinical trials. Guanhao Biotech has extensive experience in regenerative medicine and cell therapy, offering various biomaterials and cell therapy products, with several advancing to clinical trials. These companies highlight China’s progress and innovation in the stem cell drug field. With technological advancements and policy support, China is expected to achieve more breakthroughs, offering global patients expanded treatment options. SummaryThe global stem cell therapy market is projected to grow steadily, potentially exceeding $31.41 billion by 2030. The application of stem cell therapy continues to expand from hematologic diseases to neurological, cardiovascular, and metabolic disorders. With improved policies, continuous innovation, and deeper clinical applications, China's stem cell medical industry is set for broader growth prospects, offering new hope for treating refractory diseases. Personalized therapy, based on individual patient characteristics, is becoming a key trend in the industry, with customized treatment plans likely to dominate future stem cell therapies. Technological innovation and breakthroughs will further drive industry growth, providing new strategies for severe chronic diseases. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery! Refrence  1.Yamanaka S. Pluripotent Stem Cell-Based Cell Therapy-Promise and Challenges. Cell Stem Cell. 2020 Oct 1;27(4):523-531. doi: 10.1016/j.stem.2020.09.014. PMID: 33007237.2.Tewary M, Shakiba N, Zandstra PW. Stem cell bioengineering: building from stem cell biology. Nat Rev Genet. 2018 Oct;19(10):595-614. doi: 10.1038/s41576-018-0040-z. PMID: 30089805.3.Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications.

作者 | 写意君来源 | 同写意2月5日，控股诺和诺德的Novo Holdings同意通过165亿美元（约1190亿元）现金收购全球CDMO巨头Catalent。Catalent很大程度上参与了诺和诺德王牌肥胖症药物Wegovy的生产。作为本次交易的一部分，诺和诺德将以110亿美元的预付款收购Catalent在意大利、比利时和美国印第安纳州的三个灌装工厂和相关资产。新闻稿称，本次收购预计将从2026年起逐步增加诺和诺德的灌装能力。诺和诺德和礼来的降糖减肥药物之战进入白热化，面对加速膨胀的全球市场，药物供应是重要的决胜因素。去年以来，两大巨头不断加大生产基地投资以扩充产能。收购Catalent显然是诺和诺德扩大GLP-1药物商业帝国的重要一步。另一面，全球CDMO行业动荡持续加剧。本次收购案的另一方Catalent，用亲身经历写下CDMO有多“难”。最终，在2023财年营收和净利润剧降、亏损扩大146%的局面下，这家CDMO行业巨头终于找到诺和诺德这棵良木而栖。市场未来的动态变化需要更多想象力，但这笔皆大欢喜的交易背后，无论过去与未来，绝非一片坦途。01诺和诺德：近水解近渴此次交易披露后，Catalent股价上涨约10%，市值超108亿美元。诺和诺德的股价在盘前交易中上涨4.01%，市值约为5270亿美元。上周，诺和诺德市值已超过5000亿美元，其重磅药物Ozempic和Wegovy的销售额在去年创下新纪录。值得注意的是，由于供应遭遇瓶颈，Wegovy在2023年最后一个季度的销售额低于分析师的预期。Wegovy中含有的原料药（API）为司美格鲁肽，此前，诺和诺德所有API都在丹麦工厂生产。灌装工作委托给Catalent在比利时布鲁塞尔和美国印第安纳州的工厂，另外还委托了Thermo Fisher（Patheon）在北卡罗来纳州格林维尔工厂。至于注射笔装配和外包装，本来在诺和诺德自己的工厂进行，为应对市场需求，如今也委托给美国PCI Pharma Services。为了不被礼来风头正盛的替尔泊肽（Mounjaro和Zepbound）超越，诺和诺德一直在努力满足Wegovy的市场需求。去年年底，诺和诺德宣布计划建造一座价值420亿丹麦克朗（约超60亿美元）的工厂，用于生产GLP-1和其他产品API。近期，诺和诺德公开透露，运往美国的Wegovy起始剂量增加了一倍多，更多患者将能够接受治疗。在全球市场划分领地需要争分夺秒，而诺和诺德新工厂预计要到2029年才能投产。另一边，礼来则投资40亿美元在美国北卡罗来纳州建设了两座工厂，其中一座工厂位于达勒姆三角研究园区，已经开始每周7天、每天24小时连轴运行生产。在此情形下，直接买下“现货”填补产能空缺，便成了更加快捷的方法。02Catalent上半场：收购的艺术Catalent，在全球CDMO最新排名中排第四，一度风光无两。这家企业的早期历史，完美诠释了并购重组产业整合的意义。1983年嘉德诺（Cardinal Health）上市后，用二十年时间四处挑拣优质项目，组建一个制药服务部门——1996年，收购PCI用于商业化和临床试验包装的药物合同包装服务；1998年，收购RP Scherer Corporation得到商业化软胶囊生产技术；1999年，收购Automatic Liquid Packaging得到呼吸、眼科等吹灌封（BFS）技术；2002年，收购Magellan Laboratories得到药品化学分析外包技术。该部门最终在2007年，被Blackstone Group（黑石集团）收购，正式更名为Catalent。在黑石集团接手后，Catalent还延续了此前的风格。2011年，这家企业从GSK手中获得候选药物分子优化剂型解决方案平台OptiForm；2012年，通过收购临床供应商Aptuit，Catalent获得在美国、英国和新加坡的6个临床站点；2013年，Catalent先是从Redwood Bioscience获得SMARTag蛋白质工程技术，用于开发ADC，随后在中国成立两家合资企业，开拓软胶囊技术和临床试验药品包装供应业务；2014年，Catalent盈利上市。很快，Catalent就在软胶囊业务、生物药业务、口服和专业药物递送业务和临床药物供应业务板块上走到了行业前列。2017年之后，这家公司又收购印度CMO公司Cook Pharmica和颗粒工程技术全球领先提供商Micron Technologies。前期大多仅是经验的积累，不停地吃小鱼、吃大鱼，都是为了等一个在新兴赛道崛起的时机——CGT就是这个时机。2020年6月，Catalent成为首个FDA批准基因治疗商业化的CDMO。占有先手优势后，Catalent开始“卷”产能以稳固地位。2021年2月，这家公司收购了Delphi Genetics位于Gosselies的1.7万平方英尺的总部和制造工厂，增强质粒DNA制造能力。同年5月，它又收购Promethera Bioscences的细胞治疗制造子公司肝细胞治疗支持公司，增强肝脏细胞治疗领域技术，并获得超3.2万平方英尺的工厂，用于质粒DNA商业规模化生产。Catalent借助收购不断升级技术、工厂、临床供应设施，顺理成章成为基因疗法CDMO龙头。03Catalent下半场：挣扎中自救2021年9月，Catalent迎来巅峰时刻，股价也一度涨到每股130美元以上。这次飞跃，部分原因在于该公司在2020年、2021年为Moderna、强生和阿斯利康等大公司提供COVID-19疫苗生产服务，并从中获得数十亿美元的营业收入。但这次大流行只管将一些公司送上风口，能不能平稳落地，还要看各自本领。随着COVID-19疫苗需求的骤降，Catalent遇到了和赚得盆满钵满的辉瑞一样的营收压力。2023年财年里（2022年7月1日到2023年6月30日），Catalent从COVID-19产品获得的收入下降超50%，仅有6.25亿美元；第四季度同比下降70%至6500万美元。受此影响，Catalent总营收42.76亿美元，同比下降11%；净亏损2.32亿美元，同比扩大146%。为应对这一波财务危机，Catalent也拿出常规两件套自救——关厂、裁员。2022年11月，Catalent暂停了在牛津的一个疫苗生产基地建设，尽管该基地刚收购才8个月。同年12月，有报道称由于COVID-19产品收入的降低，Catalent将削减约600个工作岗位。当然，“瘦骆驼”Catalent在并购市场上更吃香了。2023年2月，彭博社报道，丹纳赫有意向收购Catalent，消息一出，Catalent股价应声上涨。但4月，该交易宣布暂停。再之后几个月，丹纳赫宣布以57亿美元收购全球抗体龙头Abcam。交易的临时转向理由不明，可Catalent的危机不止在于资金链，营收下滑背后是决定CDMO命运的生产问题。2022年9月，FDA公布了对Catalent长达19页的483表格，其中引用了8月对其位于印第安纳州布卢明顿的工厂（Catalent旗下最大的设施之一）进行的长时间调查中的12项结果，暴露出一系列Catalent的质量管控问题。FDA指出，Catalent工厂在过去两年间因可见异物问题收到了179份投诉。因生产设施问题，数百万COVID-19疫苗加强针遭扣留，Moderna的产品分发不得不推迟。这一年，Catalent比利时工厂也收到两份483表格，涉及设备问题和未经验证的备份数据等问题。2023年6月，Catalent生产设施问题直接导致再生元和拜耳合作的重磅药物阿柏西普（8mg）制剂被FDA拒绝批准。在检查过程中，FDA表示，Catalent印第安纳工厂没有遵循书面程序，设备重新验证不充分，设施及其设备没有得到充分清洁或维护。检查员记录了工厂某个区域“缺乏良好的无菌技术”以及“手套”未消毒。检查员发现一个“有凹痕的过滤器”，并表示一个生产车间处于“年久失修的状态”，胶带从墙壁上剥落、过滤器变色以及推车轮子生锈。通往物料接收平台的门“门框密封不充分”。一系列连续危机，使Catalent在去年末股价市值跌至谷底，几乎跌到巅峰时期的三分之一，股价跌幅最高曾达73.5%。这一次，Catalent终于被Novo Holdings以165亿美元收购，可以说是一笔皆大欢喜的生意。此次收购价格较Catalent消息发布前的收盘价溢价16.5%，较截至2024年2月2日的60天成交量加权平均价溢价47.5%。Novo Holdings计划在合并完成后不久，将三家工厂相关资产出售给诺和诺德。然而，它们生产设施上的遗留问题是否会进一步扩大，最终接盘的诺和诺德会获得多少实际价值，目前仍是未知数。END医药代表交流群扫描下方二维码加入医药代理商转型交流群扫描下方二维码加入

为打造全球ADC/RDC未来产业高地，成都医学城拟于2024年4月18日-19日举办首届未来XDC新药大会！大会以“共创偶联药物产业未来”为主题，由同写意策划，安排一场主论坛和九场主题论坛，邀请“政、产、学、研、金、媒”各领域专家，通过“成果发布、主题演讲、热点对话、表彰颁奖、展览展示”五位一体的多元化的组织形式，迸发更多XDC产业新科技、新业态、新模式，构建XDC产业全新生态，触摸医药产业未来脉动。2月5日，控股诺和诺德的Novo Holdings同意通过165亿美元（约1190亿元）现金收购Catalent。全球CDMO巨头Catalent，很大程度上参与了诺和诺德王牌肥胖症药物Wegovy的生产。作为本次交易的一部分，诺和诺德将以110亿美元的预付款收购Catalent在意大利、比利时和美国印第安纳州的三个灌装工厂和相关资产。新闻稿称，本次收购预计将从2026年起逐步增加诺和诺德的灌装能力。诺和诺德和礼来的降糖减肥药物之战进入白热化，面对加速膨胀的全球市场，药物供应是重要的决胜因素。去年以来，两大巨头不断加大生产基地投资以扩充产能。收购Catalent显然是诺和诺德扩大GLP-1药物商业帝国的重要一步。另一面，全球CDMO行业动荡持续加剧。本次收购案的另一方——巨头Catalent，用亲身经历写下CDMO有多“难”。从二级市场表现来看，近两年内，Catalent股价经历大跳水——从每股141.34美元的最高价跌到去年年底的每股32.18美元，市值持续蒸发。老牌CDMO在挣扎中考虑出售已是个不得已的决定，但卖身也不是说卖就能卖的——原本Catalent要被“并购之王”丹纳赫（Danaher）收购，该交易却在去年4月叫停。理由虽未公开，不过业务报告显示，Catalent生产问题和高于预期的成本，将对2023财年业绩产生重大不利影响。最终，在2023财年营收和净利润剧降、亏损扩大146%的局面下，这家CDMO行业巨头终于找到诺和诺德这棵良木而栖。市场未来的动态变化需要更多想象力，但这笔皆大欢喜的交易背后，无论过去与未来，绝非一片坦途。1诺和诺德：近水解近渴此次交易披露后，Catalent股价上涨约10%，市值超108亿美元。诺和诺德的股价在盘前交易中上涨4.01%，市值约为5270亿美元。上周，诺和诺德市值已超过5000亿美元，其重磅药物Ozempic和Wegovy的销售额在去年创下新纪录。值得注意的是，由于供应遭遇瓶颈，Wegovy在2023年最后一个季度的销售额低于分析师的预期。Wegovy中含有的原料药（API）为司美格鲁肽，此前，诺和诺德所有API都在丹麦工厂生产。灌装工作委托给Catalent在比利时布鲁塞尔和美国印第安纳州的工厂，另外还委托了Thermo Fisher（Patheon）在北卡罗来纳州格林维尔工厂。至于注射笔装配和外包装，本来在诺和诺德自己的工厂进行，为应对市场需求，如今也委托给美国PCI Pharma Services。为了不被礼来风头正盛的替尔泊肽（Mounjaro和Zepbound）超越，诺和诺德一直在努力满足Wegovy的市场需求。去年年底，诺和诺德宣布计划建造一座价值420亿丹麦克朗（约超60亿美元）的工厂，用于生产GLP-1和其他产品API。近期，诺和诺德公开透露，运往美国的Wegovy起始剂量增加了一倍多，更多患者将能够接受治疗。在全球市场划分领地需要争分夺秒，而诺和诺德新工厂预计要到2029年才能投产。另一边，礼来则投资40亿美元在美国北卡罗来纳州建设了两座工厂，其中一座工厂位于达勒姆三角研究园区，已经开始每周7天、每天24小时连轴运行生产。在此情形下，直接买下“现货”填补产能空缺，便成了更加快捷的方法。2Catalent上半场：收购的艺术Catalent，在全球CDMO最新排名中排第四，一度风光无两。这家企业的早期历史，完美诠释了并购重组产业整合的意义。1983年嘉德诺（Cardinal Health）上市后，用二十年时间四处挑拣优质项目，组建一个制药服务部门——1996年，收购PCI用于商业化和临床试验包装的药物合同包装服务；1998年，收购RP Scherer Corporation得到商业化软胶囊生产技术；1999年，收购Automatic Liquid Packaging得到呼吸、眼科等吹灌封（BFS）技术；2002年，收购Magellan Laboratories得到药品化学分析外包技术。该部门最终在2007年，被Blackstone Group（黑石集团）收购，正式更名为Catalent。在黑石集团接手后，Catalent还延续了此前的风格。2011年，这家企业从GSK手中获得候选药物分子优化剂型解决方案平台OptiForm；2012年，通过收购临床供应商Aptuit，Catalent获得在美国、英国和新加坡的6个临床站点；2013年，Catalent先是从Redwood Bioscience获得SMARTag蛋白质工程技术，用于开发ADC，随后在中国成立两家合资企业，开拓软胶囊技术和临床试验药品包装供应业务；2014年，Catalent盈利上市。很快，Catalent就在软胶囊业务、生物药业务、口服和专业药物递送业务和临床药物供应业务板块上走到了行业前列。2017年之后，这家公司又收购印度CMO公司Cook Pharmica和颗粒工程技术全球领先提供商Micron Technologies。前期大多仅是经验的积累，不停地吃小鱼、吃大鱼，都是为了等一个在新兴赛道崛起的时机——CGT就是这个时机。2020年6月，Catalent成为首个FDA批准基因治疗商业化的CDMO。占有先手优势后，Catalent开始“卷”产能以稳固地位。2021年2月，这家公司收购了Delphi Genetics位于Gosselies的1.7万平方英尺的总部和制造工厂，增强质粒DNA制造能力。同年5月，它又收购Promethera Bioscences的细胞治疗制造子公司肝细胞治疗支持公司，增强肝脏细胞治疗领域技术，并获得超3.2万平方英尺的工厂，用于质粒DNA商业规模化生产。Catalent借助收购不断升级技术、工厂、临床供应设施，顺理成章成为基因疗法CDMO龙头。3Catalent下半场：挣扎中自救2021年9月，Catalent迎来巅峰时刻，股价也一度涨到每股130美元以上。这次飞跃，部分原因在于该公司在2020年、2021年为Moderna、强生和阿斯利康等大公司提供COVID-19疫苗生产服务，并从中获得数十亿美元的营业收入。但这次大流行只管将一些公司送上风口，能不能平稳落地，还要看各自本领。随着COVID-19疫苗需求的骤降，Catalent遇到了和赚得盆满钵满的辉瑞一样的营收压力。2023年财年里（2022年7月1日到2023年6月30日），Catalent从COVID-19产品获得的收入下降超50%，仅有6.25亿美元；第四季度同比下降70%至6500万美元。受此影响，Catalent总营收42.76亿美元，同比下降11%；净亏损2.32亿美元，同比扩大146%。为应对这一波财务危机，Catalent也拿出常规两件套自救——关厂、裁员。2022年11月，Catalent暂停了在牛津的一个疫苗生产基地建设，尽管该基地刚收购才8个月。同年12月，有报道称由于COVID-19产品收入的降低，Catalent将削减约600个工作岗位。当然，“瘦骆驼”Catalent在并购市场上更吃香了。2023年2月，彭博社报道，丹纳赫有意向收购Catalent，消息一出，Catalent股价应声上涨。但4月，该交易宣布暂停。再之后几个月，丹纳赫宣布以57亿美元收购全球抗体龙头Abcam。交易的临时转向理由不明，可Catalent的危机不止在于资金链，营收下滑背后是决定CDMO命运的生产问题。2022年9月，FDA公布了对Catalent长达19页的483表格，其中引用了8月对其位于印第安纳州布卢明顿的工厂（Catalent旗下最大的设施之一）进行的长时间调查中的12项结果，暴露出一系列Catalent的质量管控问题。FDA指出，Catalent工厂在过去两年间因可见异物问题收到了179份投诉。因生产设施问题，数百万COVID-19疫苗加强针遭扣留，Moderna的产品分发不得不推迟。这一年，Catalent比利时工厂也收到两份483表格，涉及设备问题和未经验证的备份数据等问题。2023年6月，Catalent生产设施问题直接导致再生元和拜耳合作的重磅药物阿柏西普（8mg）制剂被FDA拒绝批准。在检查过程中，FDA表示，Catalent印第安纳工厂没有遵循书面程序，设备重新验证不充分，设施及其设备没有得到充分清洁或维护。检查员记录了工厂某个区域“缺乏良好的无菌技术”以及“手套”未消毒。检查员发现一个“有凹痕的过滤器”，并表示一个生产车间处于“年久失修的状态”，胶带从墙壁上剥落、过滤器变色以及推车轮子生锈。通往物料接收平台的门“门框密封不充分”。一系列连续危机，使Catalent在去年末股价市值跌至谷底，几乎跌到巅峰时期的三分之一，股价跌幅最高曾达73.5%。这一次，Catalent终于被Novo Holdings以165亿美元收购，可以说是一笔皆大欢喜的生意。此次收购价格较Catalent消息发布前的收盘价溢价16.5%，较截至2024年2月2日的60天成交量加权平均价溢价47.5%。Novo Holdings计划在合并完成后不久，将三家工厂相关资产出售给诺和诺德。然而，它们生产设施上的遗留问题是否会进一步扩大，最终接盘的诺和诺德会获得多少实际价值，目前仍是未知数。参考资料：1.JPM24 | 硝烟四起，礼来vs诺和诺德战况更新；同写意2.全球CDMO巨头Catalent成长记；药融圈3.Catalent：2023年营收、净利润双降；药融圈3.FDA公布Catalent新冠疫苗生产工厂19页483，涉及可见异物等多项质量控制问题；识林更多优质内容，欢迎关注↓↓↓