Prometheus Biosciences, Inc.

> 全球市值最高的制药公司礼来与芯片巨头英伟达近日宣布，将在未来五年内联合投入10亿美元在旧金山湾区建设AI联合创新实验室。这一重磅合作凸显美国大型制药企业作为全球医药创新体系重要力量，正从封闭研发转向开放生态，以应对研发效率下滑和专利悬崖的双重压力。 1. 传统护城河：资金、网络与监管优势 美国大型药企如辉瑞、强生、默沙东等，长期以来依靠四大核心优势主导新药研发。新药从早期研发到最终获批平均需**10至15年**，平均研发费用约**26至29亿美元**，且成本持续上升。这些企业拥有雄厚的研发资金支持，能承受前期高失败率，同时维持多个研发管线项目分散风险。 - **全球化临床试验网络**：能同步在多地招募患者进行二期和三期试验，提升数据代表性并加快进度。 - **成熟的监管对接能力**：熟悉FDA、EMA等监管体系，能有效利用“突破性疗法”“优先审评”等特殊审批通道节省时间。 - **完整产业链与规模化生产**：从原料采购到市场分销实现一体化管理，确保药物获批后迅速上市。 2. 创新焦虑：效率下滑与专利悬崖逼近 尽管优势明显，美国大型药企正面临严峻挑战。研发投入不断增加，但获批新药数量增长有限，投入产出比不高。研究显示，在进入临床试验的候选药物中，最终获得批准的比例不足**10%**。 更紧迫的是专利悬崖压力。默沙东的抗肿瘤药物Keytruda（帕博利珠单抗）2024年销售额达**294.8亿美元**，但其核心专利将在**2028年**到期，面临收入断崖风险。一旦重磅药物专利到期，仿制药涌入将导致原研药销售额大幅下滑。 3. AI赋能：从“试错”到“预测”的研发革命 为应对挑战，AI技术成为转型核心驱动力。礼来与英伟达的实验室旨在开发生成式AI模型预测药物分子特性，构建数字孪生模拟人体环境，提高临床试验预测准确性。 具体案例显示AI能大幅提升效率： - 英矽智能的TNIK抑制剂项目从靶点发现到确定临床前候选化合物仅用时**18个月**，成本约**260万美元**，远低于传统路径。 - 赛诺菲利用AI平台将某些研究流程从数周加速至仅需**数小时**，潜在活性成分识别效率提升**20%至30%**。 综合多家机构实践，AI可将研发周期缩短**60%**，综合成本降低**50%以上**。 4. 开放合作：并购与生态构建成新常态 除了内部AI应用，美国大型药企愈发注重外部创新生态合作。德勤数据显示，2024年外部引进资产在晚期管线中占比升至**61%**。 合作模式多样： - **战略投资与联合开发**：如辉瑞与多个AI初创企业合作加速研发流程。 - **并购**：诺华以**120亿美元**收购Avidity Biosciences，获得RNA疗法平台；默沙东斥资**108亿美元**收购Prometheus Biosciences强化免疫管线。 - **技术授权**：艾伯维与荣昌生物签署协议，引进双抗药物RC148，首付款**6.5亿美元**。 参与国际合作的生物医药企业，其新药上市时间平均缩短**25%**，成功率提高**15%**。 5. 临床试验优化：AI驱动效率提升 AI在临床试验设计中的应用直接加速药物上市。Medidata的AI对比模型帮助百时美施贵宝（BMS）优化CAR-T疗法试验方案，通过历史数据验证替代终点，使得该药物上市时间提前**数年**。 行业报告指出： - AI辅助的临床试验设计可将试验周期缩短**20%**，同时降低**30%**的试验成本。 - Deloitte调研显示，采用AI辅助设计平均节省研发成本**15%-20%**，整体研发周期缩短**6-9个月**。 6. 未来展望：平衡创新与可持续性 美国大型药企的转型不仅是技术升级，更是创新范式的重塑。从封闭研发到开放生态，从经验试错到数据驱动，这一变革旨在解决医药创新的根本痛点。 然而，行业也需警惕过度依赖外部收购导致的创新多样性消失。德勤报告指出，部分领域如抗微生物药物、中枢神经系统疾病等高需求治疗领域遭冷遇。可持续创新需要平衡内部研发与外部合作，聚焦未满足医疗需求。 > 英伟达CEO黄仁勋表示：“计算能力是现代药物研发的新‘实验室’。通过提供强大的AI计算平台，我们希望能够加速从靶点发现到临床试验的整个药物研发流程。” 随着AI技术持续渗透，美国大型药企的转型将深刻影响全球医药创新格局，最终推动更多突破性疗法更快惠及患者。

近日，Mirador Therapeutics公司宣布完成2.5亿美元的B轮融资，并且，公司还表示考虑年内启动IPO。 Mirador是一家相当年轻的Biotech公司，同时，兼具神秘又吸金两种特质，至今以来，Mirador已经从两轮融资中筹集到6.5亿美元，而外界对公司开发的管线以及具体适应症仍知之甚少。 Prometheus团队再创业 Mirador Therapeutics是一家2024年才成立的“初创公司”，主要专注于炎症与纤维化疾病精准药物的开发。 Mirador是主要由一家名为Prometheus Biosciences公司核心团队再创业而来，也几乎可以被视为这个团队的“续作”，两家公司几乎采用同一套精准医学理念、聚焦同一类疾病领域、聘用的同一批核心高管。 Prometheus是一家专注于免疫性疾病精准药物开发的公司，在2023年被默沙东108亿美元成功收购。 而在被默沙东收购之后，Prometheus的首席执行官Mark C. McKenna认为，公司使命尚未完成，所以把其原班人马重新又召集到一起，创立了Mirador公司。 Mirador 70%以上的核心团队成员都来自于Prometheus，包括其首席执行官&董事长-Mark C. McKenna、首席科学官-Olivier Laurent、首席医学官-Allison Luo，首席法务官-Tim Andrews、首席会计师-Vika Brough、首席人力官-Nori Ebersole、首席商务官-Jordan Zwick、事务部高级副总裁-Chris Schaumburg等在内8位高管。 而有了Prometheus被MNC巨资收购这样的“黄金履历”，Mirador的融资也变得相对容易。在没有公布任何候选管线的情况下，Mirador仅用了约60天就完成了4亿美元的A轮融资，创下临床前阶段Biotech的融资纪录。而参与该轮融的投资人也基本都是当年投过Prometheus的机构（ARCH、OrbiMed、Fairmount、Fidelity、Sanofi Ventures等），可见资本市场这一核心团队的持续认可。 “隐身式”运营 这家成立不到两年的且又十分吸金的Biotech公司，大多数时间都处于“隐身运营”状态。Mirador几乎很少对外发布公司动态（公司官网只发布过三条新闻），包括公司管线开发以及融资方面的消息。 Mirador的核心技术平台主要是Mirador360™，一种整合了患者分子图谱与人类遗传学、机器学习的技术平台，主要用于发现免疫-纤维化疾病高度相关的基因靶点，伴随诊断的同步开发，以及对患者进行分子分层，进而实现精准药物的开发。 2024年11月，公司与23andMe达成了合作，引入其全球最大众源遗传-表型数据库。 管线方面，这家公司已公开的信息很少，到现在，Mirador只有MT-501一条管线是公开的，其余的管线细节仍处于保密状态。 目前已知，这条管线已进入临床Ⅱ期阶段（适应症为炎症性肠病)，且为口服药物，但其具体靶点并未公开，公司还表示已手握“多个内部项目”，计划18个月内把多款候选药物推进至临床阶段。 参考出处 https://endpoints.news/mirador-raises-250m-with-plans-to-become-an-immunology-powerhouse/ https://www.miradortx.com/news/mirador-therapeutics-launches-accelerate-next-generation-precision-medicines-immune-mediated

After selling Morphic Therapeutic to Eli Lilly for $3.2 billion, Praveen Tipirneni is back a year and a half later with a new biotech working in Morphic’s old wheelhouse of inflammatory bowel disease. Caldera Therapeutics emerged from stealth Wednesday with a total of $112.5 million in funding for a bispecific licensed from the Chinese biotech Qyuns Therapeutics. Last April, Caldera raised a $75 million Series A round funded by Atlas Venture, LAV and venBio. Clearly deciding this was not quite enough, it has just closed a $37.5 million Series A-1 round led by Omega Funds. New investors Wellington Management and Janus Henderson Investors joined the investor lineup. “The top-up is really to provide us with runway deep into 2027,” Caldera’s chief business officer Aaron Pelta — also formerly of Morphic — told Endpoints News . “Raising the additional cash allows us a lot of operating and strategic flexibility.” The initial funding will take Caldera through its Phase 1 study of its lead candidate, a first-in-class bispecific antibody named CLD-423. This targets IL-23p19, one of the two subunits of the cytokine IL-23, and TL1A. “This is kind of the VEGFxPD-L1 for autoimmune,” Tipirneni said in the same interview, describing IL-23 and TL1A as “the two most obvious targets” in immunology. It is true that these mechanisms have seen great success. IL-23 inhibitors such as Johnson & Johnson’s Stelara and AbbVie’s Skyrizi have racked up billions of dollars in sales for immune diseases, including forms of IBD. As for the anti-TL1A pathway, it “has demonstrated incredibly strong Phase 2 clinical data over the past couple of years, and multiple pharmas have monoclonals targeting TL1A,” Pelta said. Merck bought Prometheus Biosciences for $10.8 billion in April 2023 in order to get its hands on a TL1A, and Roche paid $7.1 billion for Roivant’s TL1A six months later. Both of the drugs had posted encouraging mid-stage data in ulcerative colitis and/or Crohn’s disease. Sanofi also licensed a Phase 2-stage TL1A from Teva in late 2023. Pelta pointed out that Phase 3 studies of some of these products are due to read out this year, “and the expectation is that they will have very strong data.” The idea is that inhibiting both these pathways with a single molecule can allow potentially synergistic efficacy, Pelta said. “There’s a general belief that targeting single pathways has hit the therapeutic ceiling — efficacy has basically been capped,” he said. “The next horizon of treatment of IBD and other I&I diseases is combining complementary pathways into single bispecific molecules, to really have a step change in the efficacy.” Caldera licensed CLD-423 from Qyuns in April, paying $10 million upfront for worldwide rights. Qyuns is making a name for itself as a bispecific powerhouse. Last year, it licensed bispecifics to Roche and the Swiss biotech Windward Bio , in deals that could be worth up to $1.7 billion collectively. Pelta said that Caldera’s deal with Qyuns also provides for milestone and royalty payments, but details are under wraps. The Phase 1 trial of CLD-423 is in healthy volunteers and should conclude by the second half of this year. Phase 2 trials in IBD patients should kick off in 2027. “Depending on the final design of those studies, it could be 18 to 24 months before we see results there,” Pelta said. He added that the company is considering running a smaller Phase 1b study in patients in China, which could yield efficacy data in the first half of 2027. Long-term, Tipirneni said Caldera is focused on being the first to market with its novel mechanism rather than selling to a larger company. But having sold one company, the team will likely be expected to repeat the trick, by at least some of their backers. And Pelta points out that competing in the crowded IBD space will require more marketing might than Caldera can muster. Pending decent mid-stage data, a deal of some sort seems inevitable. Editor’s note: This article and its headline was updated to correct the total funding Caldera raised.