EpiVax, Inc.

6月2日，法国制药巨头赛诺菲（Sanofi）与美国生物制药公司BlueprintMedicines共同宣布，双方已达成收购协议。赛诺菲将以91亿美元现金+4亿美元或有价值权（CVR）的总价收购BlueprintMedicines，交易预计在2025年第三季度完成。这笔交易创下今年欧洲药企在医疗健康领域最大收购规模记录，每股129美元的收购价较Blueprint前一日收盘价溢价27%。消息公布后，Blueprint股价在盘前交易中飙升超过26%，其在中国的合作伙伴基石药业（2616.HK）也应声上涨近5%。为什么Blueprint值得95亿美元？BlueprintMedicines拥有针对系统性肥大细胞增多症（SystemicMastocytosis，SM）的靶向药物Ayvakit（通用名：avapritinib）。Ayvakit是目前全球唯一获批用于治疗晚期和惰性系统性肥大细胞增多症（ASM&ISM）的药物。这种罕见免疫疾病特征是异常肥大细胞在骨髓、皮肤、胃肠道等器官中积聚和激活，引发一系列严重症状。Ayvakit凭精准抑制能力拿下了2024年4.79亿美元净收入，2025年一季度近1.5亿美元且同比激增超60%的业绩。这种病听着小众，但异常肥大细胞在骨髓、皮肤、胃肠道等器官的疯狂累积与激活，患者极度痛苦且既往治疗选择寥寥，而Ayvakit临床缓解率能达到75%。另外，该药已进入中国首部“系统性肥大细胞增多症诊疗指南”，被推荐为一线用药，在中国市场由基石药业负责销售。赛诺菲CEO PaulHudson明确点题：收购意在“强化免疫学布局，加速转型为全球领先免疫学公司”。这句话背后，藏着两层深意：一是通过Blueprint在过敏、皮肤及免疫专科医生中成熟的学术影响力，快速打通赛诺菲自身免疫管线产品的下沉渠道；二是押注整个KIT靶点生态。Blueprint手里还攥着两张关键“未来牌”，一是Elenestinib：下一代系统性肥大细胞增多症药物，目前正在进行II/III期临床试验；二是BLU-808：高选择性口服野生型KIT抑制剂，具有治疗多种免疫性疾病的潜力。正是看中BLU-808的潜力，赛诺菲在91亿美元现金基础上，额外设置了价值4亿美元的或有价值权（CVR），若BLU-808达成特定研发和监管里程碑，股东将获得额外回报。为什么赛诺菲必须出手？赛诺菲当前的头号王牌产品是靶向IL-4R单抗药物度普利尤单抗（Dupixent）。一直以来销售额可观，贡献了制药部门绝大部分业绩，但它的专利将于2027年到期，专利悬崖的阴影已近在眼前。不止赛菲诺有这一问题，大部分大型药企超半数的营收依赖外部创新，没了并购，管线几乎“无米下炊”。未来五年内，整个行业要直面3000亿美元的专利悬崖，像强生仅一个Darzalex专利到期就得填上170亿美元的窟窿。当内部研发速度赶不上收入流失速度，“买买买”成了最直白的生存法则。如今买法也变了。前几年大家还盯着低风险、临近上市的成熟资产，现在风向陡转，早期资产、前沿技术平台成了香饽饽。礼来25亿美元押注Scorpion的早期肿瘤靶点（如KRASG12D），Moderna豪掷8.2亿美元买下临床前表观遗传编辑公司EpiVax。赛诺菲自己也是“连续买家”：上月刚收完VigilNeuroscience（4.7亿美元），去年吞下Inhibrx（22亿美元），再加上这次的Blueprint。赛诺菲在罕见病领域的布局可追溯至2011年，当时它以201亿美元收购Genzyme（健赞）。此后又通过收购Ablynx和Bioverativ，获得多款血友病新药。目前，赛诺菲在罕见病领域共布局了11条在研管线，其中6个候选产品处于III期临床。为支持这些新药产能，公司近日还宣布在法国三个生产基地投资超10亿欧元，其中仅Vitry工厂就将获得10亿欧元用于单克隆抗体产能翻倍。赛诺菲收购Blueprint也反映了中国创新角色在跨国并购版图中的悄然质变。虽然这次被购的是美国公司，但阿伐替尼的中国合作方基石药业因交易股价应声上涨近5%，这微妙折射出中国生态位的变化。中国生物技术公司已占到全球许可交易的30%以上，尤其在ADC、双抗、CAR-T领域已成输出主力。阿斯利康12亿美元全资收购亘喜生物，开了跨国药企完全吃下中国Biotech的先河；默沙东32.88亿美元引进礼新医药的双抗，BioNTech近10亿美元收购普米斯，都验证了中国创新标的价格与潜力的双重吸引力。即便美国《生物安全法案》的阴影仍在，中国研发的性价比优势和临床效率仍让国际巨头难以绕行。AI在制药业的应用已从“锦上添花”变成并购硬通货。BioNTech收购InstaDeep、Recursion豪掷7.12亿美元吞下Exscientia（创下AI制药并购纪录）等案例，凸显AI在靶点发现、分子设计、临床试验优化的全链条渗透。FDA甚至在2025年初发布了AI应用指导草案，试图规范这场技术革命。AI不只提速50%研发时间或砍半成本，更可能重构疾病治疗逻辑，能否用AI精准预测哪些免疫通路可被KIT等靶点系统性调控？这或许是赛诺菲看中Blueprint研发底层的隐性理由。当然，挑战也赤裸裸摆在眼前：数据孤岛、端到端整合难题、以及懂AI又懂药的复合人才荒，都是钱不能立刻解决的。回到患者最切身的痛点,像SM这类罕见病，真能因巨头收购而改变命运吗？从现状看，希望很大。过去SM患者基本靠抗组胺药、H1/H2受体拮抗剂甚至骨髓抑制剂勉强控制症状，但治标不治本。阿伐替尼这类精准抑制KITD816V突变的药物，是从源头上扼住疾病咽喉。赛诺菲的全球商业化能力能把阿伐替尼销售额推向更高峰值，反哺研发；其资金实力也能加速elenestinib和BLU-808的临床推进。若BLU-808成功拓展到其他免疫疾病，更将重塑整个治疗格局，比如慢性荨麻疹患者可能告别反复发作的噩梦。当然，隐患就是，95亿美元的高溢价，最终需通过药物销售额来回本。阿伐替尼虽增长快，但要在专利期内填平收购成本，需持续开拓适应症并进击新兴市场。中国虽已纳入指南和惠民保，但高值罕见病药进医保的难度众人皆知，基石药业的分成模式能否撑起赛诺菲的预期收益仍是问号，而像BLU-808这类早期分子，临床失败是常态，CVR可能沦为一张空头支票。如今，创新越来越依赖外部输血，巨头们必须学会精准评估科学价值与商业风险，买贵了伤身，错过了致命。而对无数被罕见病所困的患者来说，只要有一款像BLU-808这样的潜力药因收购获得“加速度”，便可能改变人生。参考文献：[1]赛诺菲斥资超90亿美元收购罕见病疗法公司，创欧洲药企今年收购规模之最。东方财富网，2025-06-02.[2]95亿美元！赛诺菲收购Blueprint，加速罕见免疫疾病领域布局。生物世界，2025-06-02.[3]精准医学时代的肥大细胞增多症：惰性系统性肥大细胞增多症诊疗新进展。生物通，2025-04-05.药事纵横投稿须知：稿费已上调，欢迎投稿

PROVIDENCE, R.I., April 21, 2025 /PRNewswire/ -- EpiVax, Inc. announces a new study published in Frontiers in Immunology unveiling the impact of peptides known as "Tregitopes" on antibody maturation during immune response. Lymph nodes contain antibodies that undergo changes to their sequence as they adapt to their immune target, such as a flu virus. As this happens, the content of regulatory T cell (Treg) epitope sequences (also called Tregitopes) in the antibodies appears to decrease, which enables the B cells to expand and persist. The study, "Regulatory T Cell Epitope Content in Human Antibodies Decreases During Maturation", was conducted by Andres Gutierrez, PhD and Annie De Groot, MD of EpiVax, using existing antibody sequence data. "This work provides important insights into how antibodies evolve over time, not just in terms of affinity, but in their ability to engage with the immune system." said Dr. Gutierrez. The discovery of Tregitopes in 2008 marked a shift in awareness about the function of natural Tregs in human and animal immunity. Tregitopes may explain, in part, the tolerogenic impact of IV immunoglobulin therapy (IVIG). Tregitope-like peptides have since been found in other self-proteins. A prior analysis of human antibody repertoires demonstrated that T cell epitopes decreased with increasing antibody maturation. However, that study didn't separate regulatory from effector T cell epitope dynamics. In this study, researchers examined antibody repertoires from four healthy human donors. They assessed three subsets of T cell epitopes: previously validated Tregitopes, potentially tolerated T cell epitopes and potential effector T cell epitopes. Findings revealed that as antibodies mature and have higher affinity for their target antigen, Tregitope content systematically decreases, while potential effector T cell epitope content increases. This suggests that Tregitope depletion is a fundamental feature of antibody evolution. The observation was confirmed by testing some of the 'natural' and 'modified' Tregitope sequences in vitro. "This mechanism is likely relevant to immunity from pathogens, to the development of autoantibodies during autoimmune disease, and for the selection of therapeutic antibody candidates", said Dr. De Groot. "We are pleased to contribute this finding to the literature on immune regulation and antibody design." About EpiVax EpiVax is a leader in preclinical immunogenicity assessment and sequence optimization for therapeutics and vaccines. EpiVax collaborates with globally recognized partners to accelerate immunogenicity risk assessment, immune modulation, and rapid vaccine design. Press Contact Sarah Moniz Director, Business Development [email protected] Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

PROVIDENCE, R.I., Dec. 7, 2024 /PRNewswire/ -- EpiVax, Inc., a leader in preclinical immunogenicity risk assessment for biologic and peptide therapeutics, celebrates a productive 2024 marked by scientific innovation, service diversification, and corporate growth. This year, EpiVax expanded the breadth of its immunogenicity risk assessment services with the launch of many new capabilities in the ISPRI™ ( Immunogenicity Screening and Protein Re-engineering Interface) Toolkit and many new assessment offerings. Notably, EpiVax released the ISPRI Downselect™, Quantify™, Analyze™, Evaluate™, Complete™, Optimize™, and Design™ fee-for-service analyses – options that assess biologic modalities at different stages of preclinical development, enabling the ranking of individual candidates, modality-specific benchmarking, sequence optimization and in-depth risk analyses with enhanced accuracy, and more. Class I analysis was also added to the ISPRI toolkit this year for selected gene therapy and CAR-T clients. Further, EpiVax advanced its PANDA® Screening program to support sponsors entering the FDA's Abbreviated New Drug Application (ANDA) pathway for generic peptides and their impurities. Key updates included the release of enhanced adaptive in vitro assay offerings and the Innate Immune Response Assay, establishing EpiVax as a "one stop shop" (featuring in silico, in vitro and innate assessment) for generic drug developers. Additionally, EpiVax and FDA-initiated a new contract to develop standardized controls for T cell assays which will help to improve the specificity and sensitivity of such assays industry-wide. This work was accompanied by notable contributions to the field with the publication of several highly cited articles by the EpiVax team in 2024. As a result of the expanded offerings, EpiVax immunogenicity risk assessment bookings surged nearly 60% over 2023, driven by a doubling of new clientele across the ISPRI™ Access, ISPRI™ Fee-for-Service, and PANDA® service verticals. This success supported an 18% headcount expansion, including strategic leadership additions to continue driving the company's new offerings. Looking to 2025, guided by nearly three decades of "fearless science", EpiVax is prepared to build on this year's achievements by further integrating artificial intelligence and machine learning enhancements to existing platforms, expanding laboratory capability, and adding scientific expertise that will be announced later in the new year. About EpiVax EpiVax is a leader in preclinical immunogenicity assessment and sequence optimization for peptide therapeutics, biologic therapeutics, and vaccines. EpiVax partners with a global roster of companies, agencies, and academics to accelerate immunogenicity risk assessment, immune modulation and rapid vaccine design. Press Contact Sarah Moniz Director, Business Development EpiVax [email protected] Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED