Ludwig-Maximilians-Universität München

▎药明康德编者按：在今年的欧洲产业大会——BayOConnect年会上，药明康德德国慕尼黑基地负责人Thomas Meins博士在专题对话中探讨了CRDMO模式在创新生态圈中的关键作用。在深入剖析慕尼黑生物技术生态系统的同时，他也介绍了像药明康德这样的全球合作伙伴如何赋能当地乃至全球客户，让这一生态系统更具创新活力。本文内容基于德国媒体Tagesspiegel的报道，点击“阅读全文/Read more”即可访问原文页面。慕尼黑：蓄势良久，正待腾飞慕尼黑拥有得天独厚的创新条件。该地区有着高度集中的学术资源，汇集了慕尼黑大学（LMU）、慕尼黑工业大学（TUM）、亥姆霍兹研究中心（Helmholtz Munich）、弗劳恩霍夫协会（Fraunhofer）以及马克斯·普朗克研究所（Max Planck Institutes）等国际一流科研机构，兼具科研深度与全球影响力。此外，当地生物技术初创企业不断涌现，投资规模也在迅速扩大。像BayOConnect主办方BioM这样的专业组织，致力于为创业者提供有力支持，进一步强化了本地生态体系。“2024年，德国生物技术初创企业共获得约10亿欧元风险投资，较前一年翻了一番，”Thomas Meins博士引用了BioM的2024/25年度报告中的数据，“其中大部分资金流入了大慕尼黑地区。这说明该地区的生态系统已经准备好迈入下一阶段。”在科学和资金的助力下，慕尼黑生物医药生态圈已顺利完成了从初见规模到成熟生态的演变：目前，该地区汇聚了超过520家生物技术和医药公司，拥有高度集成的服务机构网络，成为欧洲最具活力的生物技术中心之一。然而纵观新兴创新中心的成长历程，不难发现它们的发展往往并非线性，而是会在多年的基础积累之后，突然实现飞跃。对于慕尼黑而言，接下来的关键在于如何将科研实力、企业专长与资本投入，转化为可衡量的市场价值与创新成果，真正进入下一个腾飞阶段。知名生物医药中心的共性无论是美国的波士顿、旧金山、圣地亚哥，还是英国剑桥等国际知名生物医药中心，都具备一些共同特征：它们不仅拥有卓越的科研能力和活跃的投资环境，更离不开强大的综合服务体系。而在这些体系中，CRDMO组织扮演着不可或缺的角色。“CRDMO是高效生态系统的关键组成部分之一，”Meins博士表示，“它能让初创企业利用行业已经建立的成熟研发和生产体系，而无需从一开始就投入大量资金。”不仅是服务提供者，更是创新赋能者药明康德拥有独特的CRDMO模式。该模式的核心理念强调：研究（R）、开发（D）与生产（M）并非彼此割裂，而是融合为一体化服务平台。从而实现从实验室到临床应用的无缝衔接，并涵盖法规咨询、技术平台与全球化产能等多方面支持。“我们不仅是服务提供者，更是创新赋能者，”Meins博士强调，“我们的使命是帮助客户更快、更安全、更成功地将产品推向市场，同时为投资者提供他们需要的规模和规划确定性。”CRDMO模式降低了开发风险，缩短了产品上市周期，并增强了初创企业对投资者的吸引力。因此，它不仅在技术层面，也在经济层面直接推动生物技术创新的成功。「欧洲医药高地」的长远布局早在2016年，药明康德便通过收购专注于生物物理和基于结构的药物发现的Crelux公司，展现了对慕尼黑地区的坚定信心。如今，这一已有近20年历史的慕尼黑基地，专注于早期药物发现，重点深耕晶体学、蛋白生物化学与生物物理等领域。与此同时，药明康德持续为行业合作伙伴提供高质量服务。今年，慕尼黑基地顺利通过德国联邦药品和医疗器械管理局（BfArM）的GMP检查，并获得欧盟生产/进口许可证（MIA）与GMP认证。这一里程碑标志着公司正式启动面向欧盟市场的产品批次放行服务（Qualified Person，简称QP），能够为面向欧盟的生物技术公司简化进口流程，加快药物惠及患者的速度。作为药明康德全球CRDMO网络中专注于研究（R）的关键节点，慕尼黑的科研专长与其他基地的开发（D）和生产（M）能力形成互补。例如，药明康德化学业务平台在瑞士的库威（Couvet）基地正在扩建新的生产设施。2025年5月，该基地启动全新喷雾干燥制备固体分散体（SDD）车间建设，预计将于2026年第四季度投入运营。该设施将有助于提升低水溶性化合物的生物利用度。通过整合慕尼黑基地的发现能力、瑞士基地的生产能力，以及全球一体化服务网络，药明康德为欧洲生物技术企业提供更快速的产品上市路径，从而助力本地创新能力的提升。“药明康德已经深度融入慕尼黑的科研生态多年。我们在全球持续拓展的同时，也在本地不断加大投入。”Meins博士强调，“我们希望吸引更多生物技术企业与我们携手合作，共同增强区域生态系统的活力。”展望：下一轮腾飞的关键“我们需要新一代生物技术公司，它们不仅要实现快速增长，还要具备长期战略，专注于可持续发展、稳健的产品管线以及国际化拓展。”Meins博士指出，“这需要一个能够支持这些愿景的生态体系，包括覆盖各阶段的资本支持、现代化基础设施、法规专业能力与可信赖的合作伙伴。”目前，药明康德的活跃客户数约6000家，涵盖初创企业及全球大型医药公司，是生物医药行业重要的一体化服务平台之一，也是推动区域创新生态发展的重要力量。展望未来，药明康德希望与当地及全球的合作伙伴一道，继续推动这一进程，加速慕尼黑地区的产业腾飞。我们也期待通过加强与创业者、科学家及投资人的持续合作，以及对欧洲基地的不断升级扩建，以全方位行动践行承诺，早日实现“让天下没有难做的药，难治的病”的愿景。Model Region Munich: With companies like WuXi AppTec, Munich is becoming Europe’s leading biotech hubDr. Thomas Meins, head of WuXi AppTec’s Munich site, spoke at this year’s BayOConnect about the role of CRDMOs and how to align scientific vision with investor interests. A good reason to take a closer look at the growth dynamics of the Munich ecosystem and how global partners like WuXi AppTec are supporting this process. Where does Munich stand on the biotech success curve?The growth of emerging innovation hubs rarely follows a linear path — it often takes years of groundwork before a region truly takes off. Munich has successfully completed this maturing process in recent years: with over 520 biotechnology and pharmaceutical companies and a dense network of service providers, the region is now one of the most dynamic biotech hubs in Europe. The big question is: when will the actual growth phase begin — the moment when scientific strength, entrepreneurial expertise, and capital inflow translate into measurable market and innovation growth?Many refer to this as the ‘hockey-stick growth’ — a sudden surge following a longer preparatory phase.The conditions could hardly be better: Munich impresses with an exceptional density of academic excellence. Institutions such as LMU, TUM, Helmholtz Munich, Fraunhofer, and the Max Planck Institutes stand for top-tier research and international appeal.Added to this is a growing number of ambitious biotech start-ups and sharply increasing investments. This development is supported by specialized cluster initiatives like BioM, the organizer of BayOConnect, which provides targeted support to founders.“German biotech start-ups raised around 1 billion euros in venture capital in 2024, twice as much as the previous year,” quotes Dr. Thomas Meins from the BioM Annual Report 2024/25. “A large part of this flowed into the Greater Munich area. That shows: the ecosystem is ready for the next step.”What distinguishes successful biotech hubs?Looking at internationally successful biotech centers like Boston, San Francisco, Cambridge (UK), or San Diego reveals common features: not only excellent research and an active investor environment, but also powerful, integrated service structures. Contract Research, Development, and Manufacturing Organizations (CRDMOs) play a central role.“CRDMOs are a crucial component of functioning ecosystems,” says Dr. Meins. “They give young companies access to industrially established research, development, and manufacturing structures without having to make massive investments from the outset.”The CRDMO model: Enabler rather than mere service providerWuXi AppTec has been a key driver of the CRDMO model. The idea: research (“R”), development (“D”), and manufacturing (“M”) are not offered in isolation, but combined in an integrated service model. The result is a seamless transition from the laboratory to clinical application, including regulatory advice, technology platforms, and global production capacities.“We see ourselves not just as a service provider but as an enabler of innovation,” emphasizes Dr. Meins. “Our mission is to help our customers reach the market faster, more safely, and more successfully, while offering investors the scalability and planning certainty they need.”The CRDMO approach reduces development risks, shortens time-to-market, and makes young companies more attractive to investors. In this way, it contributes directly to the success of biotech innovations — not only technologically, but also economically.Munich as a strategic locationAs early as 2016, WuXi AppTec showed its confidence in the Munich location by acquiring the drug discovery service provider Crelux, a specialist in biophysical and structure-based drug discovery. Today, the Munich site, established nearly 20 years ago, has been expanded and focuses on early-stage drug discovery, particularly in crystallography, protein biochemistry, and biophysics.Equally important is the high quality that WuXi AppTec delivers to the industry. This year, WuXi AppTec’s Munich site successfully passed the GMP inspection by the BfArM and received the Manufacturing/Import Authorization (MIA) as well as EU-GMP certification. This milestone marks the official launch of WuXi AppTec’s EU release services, also known as Qualified Person (QP) services. This enables simplified import for biotech companies with EU-oriented programs and shortens the time to patient access.As the “R” site (research) in WuXi AppTec’s global CRDMO network, Munich’s research expertise complements the strengths in “D” (development) and “M” (manufacturing) of other sister sites — such as the expanding production facility in Switzerland.In May 2025, ground was broken for a new spray dried dispersion (SDD) manufacturing building at the Couvet site in Switzerland. Operations are expected to start in the fourth quarter of 2026. The facility will help improve the bioavailability of poorly water-soluble compounds. By combining Munich’s discovery expertise with Switzerland’s production capacity and all other required capabilities, WuXi AppTec offers European biotech companies faster market access, thereby strengthening local innovation capacity.“WuXi AppTec has been firmly anchored in Munich’s research landscape for many years. We have been expanding our expertise worldwide for years while continuing to grow locally,” says Dr. Thomas Meins. “Today, we want to attract more biotech companies into our orbit and jointly contribute to the strength of the ecosystem.”With around 6,000 active customers worldwide, ranging from small start-ups and stealth-mode companies to the top 20 pharma companies, WuXi AppTec is one of the leading end-to-end service providers in the biopharma industry and an active shaper of regional innovation landscapes.Outlook: How can Munich achieve its next growth spurt?“We need a new generation of biotech companies that, in addition to rapid growth, also pursue long-term strategies — with a clear focus on sustainable development, robust pipelines, and internationalization,” says Dr. Meins. “This requires an ecosystem that supports these ambitions — with capital for all growth phases, modern infrastructure, regulatory expertise, and reliable partnerships.”WuXi AppTec aims not just to participate in this process, but to actively lead it. Its presence at BayOConnect, its ongoing collaboration with founders, universities, and investors, and the further development of its Munich site all reflect this ambition.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「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

来自慕尼黑大学等机构的科学家们通过研究首次发现，Ψ-RNA的“隐身术”源于溶酶体核酸酶RNase T2和PLD外切酶的“选择性失明”以及TLR7/8受体的“双重忽视”。 2025年，全球mRNA疫苗累计接种已超百亿剂次，其高效性与安全性彻底改写了传染病防控的格局。从新冠疫苗到癌症治疗，mRNA技术正以惊人的速度渗透医学领域。然而，回溯至2005年，科学家Karikó团队首次发现，将mRNA中的尿苷（U）替换为假尿苷（Ψ），可显著降低免疫原性，这一发现成为mRNA疗法的“阿基米德支点”。但为何Ψ-RNA能逃避免疫系统的安检？ 免疫系统中的Toll样受体7/8（TLR7/8）如同“核酸探测器”，其能专门识别病毒RNA降解产物从而触发炎症反应。而人体自身RNA因含Ψ等修饰，却能“蒙混过关”。这一现象不仅能解释mRNA疫苗的低免疫原性，更揭示了生命进化中自我-非我识别的精妙机制。 近日，一篇发表在国际杂志Cell上题为“Pseudouridine RNA avoids immune detection through impaired endolysosomal processing and TLR engagement”的研究报告中，来自慕尼黑大学等机构的科学家们通过研究首次发现，Ψ-RNA的“隐身术”源于溶酶体核酸酶RNase T2和PLD外切酶的“选择性失明”以及TLR7/8受体的“双重忽视”。 mRNA疗法的成功依赖于Ψ修饰的免疫沉默特性，但其分子机制长期成谜。这项研究中，研究人员旨在揭示Ψ-RNA如何通过溶酶体加工和TLR识别双重关卡实现免疫逃逸，从而为设计更安全的RNA药物提供一定的理论依据。 文章中，研究人员采用体外转录的Ψ-RNA、m1Ψ-RNA（N1-甲基假尿苷）及未修饰RNA作为模型，并结合人源单核细胞、树突状细胞及TLR8/7基因敲除细胞系，系统评估免疫激活差异。研究中所用的关键试剂包括RNase T2、PLD3/4外切酶及TLR特异性抑制剂（如CU-CPT9a）。 Ψ-RNA并不会激活TLR8 研究发现，RNase T2对Ψ-RNA的切割效率较未修饰RNA下降超90%，且PLD外切酶同样难以降解Ψ-RNA。在细胞模型中，Ψ-RNA几乎无法激活TLR7/8依赖的炎症因子（如IL-6、IFN-α），而m1Ψ-RNA虽能微弱激活TLR8，但仍显著弱于未修饰RNA。 进一步通过核磁共振（NMR）研究发现，Ψ-RNA倾向于形成A型螺旋构象，从而就会导致RNase T2的B2结合口袋无法适配，同时Ψ的N1位甲基化回进一步阻碍PLD外切酶的结合。 Ψ-RNA的免疫沉默并非单一机制，而是双保险。一方面，RNase T2和PLD外切酶无法有效切割Ψ-RNA，从而导致TLR7/8配体生成受阻；另一方面，TLR8的第一结合口袋忽视Ψ，TLR7的第二结合口袋则拒绝Ψ-RNA片段。 这项研究中，研究人员首次系统揭示了Ψ-RNA免疫逃逸的分子细节，其意义远超mRNA疫苗领域。Ψ修饰可能是真核生物进化出的自我标记，其能通过干扰核酸酶和TLR的识别从而避免自身免疫攻击。这一发现不仅巩固了mRNA疗法的基石，更为RNA药物设计提供了“精准调控免疫原性”的新思路。 m1Ψ虽保留了部分TLR8激活能力，但其免疫原性仍远低于未修饰RNA，这就提示，未来RNA药物或能通过微调修饰位点的平衡疗效与安全性。LC-MS与NMR联用则为RNA修饰研究提供了高分辨率工具，未来或有望解析更多免疫隐身修饰（如2'-O-甲基化）的机制。 正如研究人员所言：“理解Ψ-RNA如何骗过免疫系统就像破解了RNA世界的“隐身斗篷”，下一次疫苗革命或许就藏在下一个Ψ里。”（生物谷Bioon.com） 参考文献： Marleen Bérouti，Mirko Wagner，Wilhelm Greulich, et al. Pseudouridine RNA avoids immune detection through impaired endolysosomal processing and TLR engagement, Cell (2025). DOI:10.1016/j.cell.2025.05.032

Arctic Bioscience is pressing ahead with plans to develop its oral psoriasis treatment HRO350 despite the drug's failure to succeed in a Phase IIb trial. The Norwegian biotech, which develops products based on herring roe compounds, provided a detailed analysis of 12-month data from the HeROPA study first toplined in April, sending its shares up as much as 37% on Wednesday.The 521-patient trial tested HRO350 against placebo in patients with mild-to-moderate psoriasis, but failed to demonstrate a statistically significant difference on the primary endpoint of 50% reduction in the Psoriasis Area and Severity Index (PASI50) at six months due to an "unexpectedly high" placebo response.However, Arctic said encouraging signals emerged from secondary endpoints and subgroup analyses that justify continued development. Nearly half of patients (47%) in the high-dose arm achieved Physician's Global Assessment score of either "cleared" or "almost clear" (PGA 0/1) after 52 weeks compared to 34% on placebo, a difference that "approaches significance," the company reported.Placebo 'mystery'According to Arctic, "natural disease fluctuations and limited precision on [the] lower end of PASI scale makes it hard to show differences in PASI50 between groups for patients with mild-to-moderate psoriasis." By contrast, it said PGA 0/1 is easier to measure, but a much harder endpoint to achieve.The company noted that post-hoc analyses revealed that patients with more severe baseline disease (PASI ≥6), those 50 years and older, and those weighing less than 98 kg showed better responses to treatment than placebo. "There is an effect in the treatment groups, the mystery is placebo, which we need to understand better in order to design a next study with HRO350," said principal investigator Ingeborg Bachmann.HRO350 contains a proprietary lipid extract derived from herring roe that works by promoting the production of specialised pro-resolving mediators (SPMs), bioactive lipids that actively terminate inflammation rather than simply blocking it. Arctic suggests the mechanism sets its oral treatment apart from existing therapies that primarily inhibit pro-inflammatory cytokines.The company said HRO350 demonstrated a favourable safety profile throughout the year-long study with no drug-related serious adverse events reported.Seeking partnerships"We are encouraged by the efficacy and safety profile of HRO350. These results reinforce our belief in the potential of this asset to address chronic conditions like psoriasis," said CEO Christer Valderhaug. The company "strongly [believes] there is a major market potential for HRO350 in mild-to-moderate psoriasis and will seek partnerships for further development."In an investor presentation this week, Arctic indicated it plans to move HRO350 into Phase III development in 2025.