食欲素存在的大部分时间里，是一门漂亮的基础科学，也是一个棘手的商业题目。进入 2026 年，它成了一类被定过价的资产。短短几个月内，礼来完成了对 Centessa Pharmaceuticals 及其食欲素激动剂管线的收购；首个食欲素受体激动剂在五周之内先后进入三个主要市场；9 月，Lasker 基金会把 Albert Lasker 基础医学研究奖授给两位科学家，正是他们在一代人之前发现了食欲素，并证明它的缺失会造成发作性睡病。谁要是还把睡眠归进神经科学的次要类目，不妨把这三件事放在一起再读一遍。For most of its life, orexin was a beautiful piece of basic science and a difficult commercial subject. In 2026 it became a priced asset class. Within a few months, Eli Lilly closed its acquisition of Centessa Pharmaceuticals and its orexin agonist pipeline; the first orexin receptor agonist was approved in three major markets in the space of five weeks; and in September, the Lasker Foundation gave its Albert Lasker Basic Medical Research Award to the two scientists who, a generation earlier, had identified orexin and shown that its absence causes narcolepsy. Anyone who still files sleep under minor neuroscience categories should re-read those three facts together.
有必要说准食欲素与 GLP-1 之间被谈论得很多的那层关联：它是什么，不是什么。食欲素是下丘脑的神经肽系统，稳定清醒，也参与摄食、奖赏与能量消耗。GLP-1 系统在解剖上与它相交：2004 年的研究已经显示，GLP-1 能兴奋食欲素神经元，食欲素神经元又投射到脑干中产生 GLP-1 的区域。这类证据几乎全部来自临床前研究。没有研究证明已获批的 GLP-1 药物在病人体内通过食欲素起效，也没有任何双机制联合方案在临床开发中；小鼠实验里那个提示性的结果，即增强食欲素信号可以抵抗饮食诱导的肥胖，据我们检索，也没有产生一个临床阶段的减重项目。交汇是真的，只是就目前而言，它交汇在适应症和产品组合上，不在分子上。It is worth being precise about what the much-discussed link between orexin and GLP-1 is, and what it is not. Orexin is a hypothalamic neuropeptide system that stabilizes wakefulness and also participates in feeding, reward, and energy expenditure. The GLP-1 system intersects with it anatomically: in work dating to 2004, GLP-1 was shown to excite orexin neurons, and orexin neurons in turn project to brainstem regions where GLP-1 is produced. Nearly all of that evidence is preclinical. No study has shown that approved GLP-1 medicines work through orexin in patients, no combination of the two mechanisms is in clinical development, and the suggestive mouse work linking enhanced orexin signaling to resistance to diet-induced obesity has produced no clinical obesity program that we can find. The convergence is real, but at present it is a convergence of indications and of portfolios, not of molecules.
阻断食欲素来得更早。三款双食欲素受体拮抗剂 suvorexant（2014）、lemborexant（2019）和 daridorexant（2022）都已拿到 FDA 的失眠批准，十年的使用确立了这个靶点可成药、这一类药经得起时间。现在更值得问的是，拮抗作用能走出失眠多远。强生的 seltorexant 是一种选择性食欲素受体 2 拮抗剂，曾在伴有失眠症状的重性抑郁障碍中作辅助治疗进行试验。2025 年 9 月公布的 III 期 MDD3005 研究中，它的应答率在数值上高于喹硫平缓释片（57.4% 对 53.4%），但主要终点没有达到统计学显著；耐受性对 seltorexant 有利，嗜睡更少，体重增加也更少（平均 0.5 公斤对 2.1 公斤）。这就是这个领域扩张的诚实形状：药理上走得出去，走多远由终点决定。Blocking orexin came first. Three dual orexin receptor antagonists — suvorexant (2014), lemborexant (2019), and daridorexant (2022) — hold FDA approvals for insomnia, and a decade of use has established the target as druggable and the class as durable. The interesting question now is how far antagonism travels beyond insomnia. Johnson & Johnson's seltorexant, a selective orexin-2 receptor antagonist, was tested as an adjunctive treatment for major depressive disorder with insomnia symptoms. In the Phase 3 MDD3005 study reported in September 2025, response rates were numerically higher than with quetiapine extended-release (57.4 percent versus 53.4 percent), but the primary endpoint did not reach statistical significance; tolerability favored seltorexant, including less somnolence and less weight gain (an average of 0.5 kg versus 2.1 kg). That is the honest shape of expansion in this field: the pharmacology travels, and the endpoints decide.
激活食欲素更难，分量也更重，因为发作性睡病 1 型是一种缺失性疾病：患者大脑里产生食欲素的神经元本身已经丧失。武田的 oveporexton 是口服食欲素受体 2 激动剂，在两项全球 III 期研究中达到了全部主要和次要终点，第 12 周各剂量的 p 值均小于 0.001。监管机构随即接连动作：2026 年 7 月 22 日中国批准，8 月 5 日美国批准，日本也在同五周内批准。FDA 对 oveporexton 的说法是，首个把发作性睡病 1 型作为一种完整疾病来治疗的药物，也是首个直接针对其成因，也就是食欲素信号缺失，的药物。不过，批准不等于有货：美国以外市场已于 10 月开始上市，美国的上市定在 2026 年 11 月，要等 Drug Enforcement Administration 完成管制分级。Activating orexin is the harder and more consequential direction, because narcolepsy type 1 is a deficiency disease: the brain has lost the orexin-producing neurons themselves. Takeda's oveporexton, an oral orexin receptor 2 agonist, met every primary and secondary endpoint in two global Phase 3 studies, with p-values below 0.001 across all doses at week 12. Regulators then moved in quick succession: approvals in China on July 22, 2026, in the United States on August 5, 2026, and in Japan within the same five-week span. The FDA described oveporexton as the first medicine approved to treat narcolepsy type 1 as a complete disorder, and the first to work by directly targeting the loss of orexin signaling that causes it. Approval, however, is not availability: launches outside the United States began in October, while the U.S. launch is set for November 2026, following completion of Drug Enforcement Administration scheduling.
先行者不会独行太久。Alkermes 已报出 alixorexton 在发作性睡病 1 型和 2 型上的 II 期阳性结果，2026 年 4 月启动了全球 III 期 Brilliance 项目，1 型数据已发表于 The Lancet Neurology。它身后是礼来新近收购的 cleminorexton，已有覆盖发作性睡病 1 型、2 型和特发性嗜睡症的 IIa 期数据。在这个领域，先行者的优势更可能以读出之间的间隔计，而不是以年计。The first mover will not be alone for long. Alkermes has reported positive Phase 2 results for alixorexton in both narcolepsy type 1 and type 2, initiated its global Phase 3 Brilliance program in April 2026, and seen the type 1 data published in The Lancet Neurology. Behind it sits Lilly's newly acquired cleminorexton, with Phase 2a data across narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. In this field, a pioneer's advantage is likely to be measured in readout intervals rather than in years.
至于 GLP-1，它是从代谢一侧走进睡眠的，走的是完全不同的一条路。2024 年 12 月 20 日，FDA 批准 tirzepatide 治疗伴有肥胖的成人中重度阻塞性睡眠呼吸暂停，这是该病有史以来第一个获批的药物。FDA 的解释走的是体重这条线：药物激活 GLP-1 与 GIP 受体，减少食欲与体重，体重降下来，睡眠呼吸暂停随之改善。这里必须说精确，因为这一类药常被当成共享同一个标签来谈。截至本文写作时，这一类里只有一个分子握有睡眠适应症，semaglutide 没有。把这个区别抹掉的交汇叙事，经不起认真读者的细看。GLP-1, meanwhile, has entered sleep from the metabolic side, by a completely different route. On December 20, 2024, the FDA approved tirzepatide for moderate to severe obstructive sleep apnea in adults with obesity, the first medication ever approved for that condition. The agency's own explanation was weight-mediated: the drug activates receptors for GLP-1 and GIP, reduces appetite and body weight, and, by reducing body weight, improves sleep apnea. Precision matters here, because the class is often discussed as if the label were shared. As of this writing, only one molecule in the class holds a sleep indication; semaglutide does not. A convergence narrative that ignores that distinction will not survive a careful reader.
产品组合层面的交汇，才是这个故事里属于交易人的部分。2026 年 3 月 31 日，礼来宣布收购 Centessa，出价为每股 38.00 美元现金，加一份每股最高 9.00 美元的或有价值权：首笔股权价值约 63 亿美元，或有里程碑达成时最高再加约 15 亿美元。礼来正是拥有业内标志性 GLP-1/GIP 产品组合的那家公司。交易已于 2026 年 6 月 24 日交割。Centessa 的食欲素激动剂系列以 cleminorexton 为首，与日本 Nxera Pharma 共同发现，Nxera 在这些项目中保留了里程碑付款与销售分成的权益。也就是说，这条价值链在成为礼来的之前，本就是跨境的。这笔交易的话很直白：业内最强的代谢产品组合认定，睡眠与清醒的生物学应该装进同一个组合里。The portfolio convergence is the part of the story that belongs to dealmakers. On March 31, 2026, Lilly — the company that owns the defining GLP-1/GIP franchise — announced that it would acquire Centessa for $38.00 per share in cash plus a contingent value right worth up to $9.00 per share: an upfront equity value of approximately $6.3 billion, with up to approximately $1.5 billion more if the contingent milestones are met. The transaction closed on June 24, 2026. Centessa's orexin agonist series, led by cleminorexton, was co-discovered with Nxera Pharma of Japan, which retains milestone and royalty rights in the programs. The value chain, in other words, was cross-border before it was Lilly's. What the deal says is simple: the strongest metabolic franchise in the industry decided that sleep-wake biology belonged in the same portfolio.
现在给食欲素资产定价的人，有三件事要盯住。第一，这一类药有一堂记录在案的肝脏课：武田较早的激动剂 TAK-994 在 2021 年出现肝毒性信号后暂停给药，项目随之终止；该研究 2023 年发表于 The New England Journal of Medicine 时，载有符合 Hy's law 标准的药物性肝损伤病例。在食欲素的尽职调查里，肝功能指标不是脚注，是第一页。第二，管制分级就是经济学：oveporexton 8 月获批，美国上市却在 2026 年 11 月，中间这道缝提醒人，受管制物质的身份要进估值模型，不只是进监管计划。第三，扩张由读出决定：食欲素激动能否有说服力地从发作性睡病 1 型扩到 2 型与特发性嗜睡症，GLP-1 这一类又能否靠专门的试验在睡眠里继续推进，而不是只靠减重的溢出。Three things deserve attention from anyone pricing orexin assets now. First, the class carries a documented liver lesson: Takeda suspended dosing of its earlier agonist, TAK-994, in 2021 after a liver toxicity signal emerged; the program was discontinued, and the study's eventual publication in The New England Journal of Medicine in 2023 included cases meeting Hy's law criteria for drug-induced liver injury. Liver chemistry is not a footnote in orexin diligence; it is the first page. Second, scheduling is economics: the gap between oveporexton's August approval and its November 2026 U.S. launch is a reminder that controlled-substance status belongs in valuation models, not only in regulatory plans. Third, expansion will be decided by readouts: whether orexin agonism extends convincingly from narcolepsy type 1 to type 2 and idiopathic hypersomnia, and whether the GLP-1 class advances in sleep through dedicated trials rather than through the spillover of weight loss.
Megs 创立于 2010 年，2016 年起从事跨境交易；我们标题所指的那项工作，也就是连接中国与美国之间的项目方和投资人，越来越多地落到这样的领域里：科学、资产和交易对手分处不同体系。睡眠和代谢，分开谈了一代人。2026 年的这些事说明，它们不会再一直分开。我们的角色依然不大：帮每一方看清，对方到底在看什么。Megs was founded in 2010 and has worked on cross-border transactions since 2016; the work described by our headline — Connecting Project Sponsors and Investors Between China and the U.S. — increasingly involves fields, like this one, where the science, the assets, and the counterparties sit in different systems. Sleep and metabolism were separate conversations for a generation. The events of 2026 suggest they will not remain so. Our role remains a modest one: to help each side understand what the other side is actually looking at.