莫德纳的癌症疫苗过去一周通过了其首个重大考验。更大的问题在于，其股价的定价仿佛该疫苗已经通过了所有考验。
Moderna’s cancer vaccine passed its first big test this past week. The bigger problem is that its stock is priced as if it has already passed them all.
自新冠疫情以来，莫德纳一直是一只波动剧烈的股票。其市值在2021年曾逼近2000亿美元，随后随着疫苗销售额的暴跌而崩盘，并在去年触底，跌至约100亿美元。
Moderna has been a hugely volatile stock since the Covid-19 pandemic. Its value peaked near $200 billion in 2021, then collapsed along with vaccine sales, bottoming at about $10 billion last year.
n最新一轮暴涨始于今年8月，当时莫德纳与合作伙伴默克公司宣布，在一项大型试验中，他们的个性化注射疫苗降低了黑色素瘤患者手术后复发的风险。尽管许多分析师认为这是一个科学里程碑，但其适用范围能否超出黑色素瘤尚未得到证实，而该股在两个月内近乎翻了两番。
The latest big rally began in August, when Moderna and partner Merck said their personalized shot cut the risk of melanoma returning after surgery in a large trial. The stock nearly quadrupled in two months, even though many analysts saw a scientific milestone whose reach beyond melanoma was still unproven.
过去一周，详细数据公之于众，这也带来了一次现实的检验。周四数据泄露后，莫德纳股价截至周五下跌了约20%，这促使两家公司在马德里举行的重大肿瘤学会议上原定展示日期的两天前公布了数据。
This past week came the details, and a reality check. Moderna shares fell about 20% through Friday after results leaked Thursday, prompting the companies to release data two days before their planned presentation at a major oncology conference in Madrid.
尽管数据略逊于最乐观的期望，但它确实兑现了诺言。在1137名经手术切除黑色素瘤的患者中，将该疫苗与默克公司的免疫疗法Keytruda结合使用，与单用Keytruda相比，癌症复发或死亡的风险降低了42%。这越过了投资者设定的约40%的门槛，应该足以赢得批准。
The data itself delivered, even if it fell short of the most bullish hopes. Among 1,137 patients whose melanoma had been surgically removed, adding the vaccine to Merck’s immunotherapy Keytruda cut the risk of the cancer returning, or of death, by 42% compared with Keytruda alone. That cleared the roughly 40% bar investors had set, and should be enough to win approval.
然而，该股票在数据发布前所蕴含的期望值实在太高了。算一笔账：分析师通常按一款药物峰值年销售额的四倍左右来对其进行估值。根据分析师的估计，获批的黑色素瘤疗法年销售额可能达到约40亿美元。与默克公司平分后，莫德纳的峰值销售额约为20亿美元，市值大约相当于80亿美元。
But expectations built into the stock prior to the release were far too high. Consider the math. Analysts often value a drug at roughly four times its peak annual sales. An approved melanoma treatment could reach about $4 billion a year, according to analyst estimates. Split with Merck, that is about $2 billion in peak sales for Moderna, worth roughly $8 billion in market capitalization.
然而，即便在经历了最近的抛售之后，莫德纳的市值仍比8月份的消息公布前高出约550亿美元。这实际上计入了这样一种情景：该疫苗在多种肿瘤中均有效，且规模几乎能与全球最畅销的抗癌药Keytruda相媲美。
Yet even after the latest selloff, Moderna is worth about $55 billion more than before the August news. That essentially prices in a scenario where the vaccine works across several tumors and becomes nearly as big as Keytruda, the world’s bestselling cancer drug.
看涨的理由在于该方法的创新之处。肿瘤携带有能产生异常蛋白质的突变，免疫系统能够识别这些蛋白质。莫德纳对每位患者的肿瘤进行测序，利用算法选出最多34个最有可能引发免疫反应的靶点，并使用与其新冠疫苗相同的技术将其编码进mRNA注射液中。这实际上是一记“组合拳”：Keytruda解除免疫系统的刹车，而疫苗则为其提供要搜寻的具体靶点。
The bull case rests on what makes the approach novel. Tumors carry mutations that can produce abnormal proteins the immune system can recognize. Moderna sequences each patient’s tumor, uses an algorithm to select up to 34 targets most likely to provoke an immune response, and encodes them in an mRNA shot, using the same technology as its Covid vaccine. It is effectively a one-two punch in which Keytruda takes the brakes off the immune system and the vaccine provides it with the specific targets to hunt.
由于突变在各类癌症中都很常见，投资者希望这种方法能被证明是一个适用于许多癌症（从肺癌、肾癌到膀胱癌）的平台。但这依然是一场押注于尚未报告结果的试验的博弈。黑色素瘤可以说是这种方法所能要求的最佳测试场。黑色素瘤肿瘤携带着大量突变，为疫苗提供了充足的靶点来训练免疫系统进行识别。而且它们往往属于“热”肿瘤，意味着免疫细胞已经到达现场。许多其他肿瘤的突变较少，或者更善于躲避免疫系统，因此该疫苗在其他地方面临着更高的门槛。
Because mutations are common across cancers, investors hope the approach will prove to be a platform that works for many of them, from lung to kidney to bladder. But that remains a bet on trials that haven’t yet reported results. And melanoma is about as favorable a testing ground as this approach could ask for. Melanoma tumors carry lots of mutations, giving the vaccine plenty of targets to train the immune system to recognize. And they tend to be “hot,” meaning immune cells are already on the scene. Many other tumors carry fewer mutations or are better at hiding from the immune system, so the vaccine faces a higher bar elsewhere.
另一个担忧是：黑色素瘤的治疗方式正在发生变化。医生越来越多地在手术前以及手术后使用Keytruda，以帮助免疫系统识别癌症。在另一项研究中，这种方法的治疗效果有所改善，一些分析师称其幅度与疫苗相似，尽管这些试验无法直接进行对比。这就给一种售价可能在30万美元左右的个性化注射疫苗提出了一个尴尬的问题：为什么不早点使用Keytruda，尤其是当其专利在2028年到期后出现更便宜的仿制药时？
Another worry: how melanoma is treated is changing. Doctors increasingly give Keytruda before surgery, as well as after, to help the immune system recognize the cancer. In a separate study, that approach improved outcomes by a margin some analysts say is similar to the vaccine’s, though the trials aren’t directly comparable. That raises an awkward question for a personalized shot that could cost around $300,000: Why not just give Keytruda earlier, especially once cheaper copies arrive after its patent expires in 2028?
并非每个患者都适合，而且这两种方法也可以结合使用。但这种转变可能会侵蚀该疫苗最明显的市场。
Not every patient is a candidate, and the two approaches could be combined. But the shift could chip away at the vaccine’s most obvious market.
该试验还追踪了患者的癌症是否扩散到其他器官（如肺部或大脑），这是导致黑色素瘤死亡的主要原因。在这方面，大约两年后，该疫苗将癌症扩散或死亡的风险降低了38%。在先前规模较小的一项试验中，五年后该风险降低了59%。莫德纳向分析师表示，这一差距在一定程度上反映出这项大型试验纳入了病情处于更早期的癌症患者，而这些患者的癌症扩散需要更长的时间。
The trial also tracked whether patients’ cancer spread to other organs, such as the lungs or brain, which is the main driver of melanoma deaths. On that score, the vaccine cut the risk of spread or death by 38% after about two years. In an earlier, smaller trial, it had cut it by 59% after five years. Moderna has told analysts the gap partly reflects the larger trial’s inclusion of patients with earlier-stage cancer, which takes longer to spread.
这些都无损于其科学价值。改进Keytruda——史上最有效的抗癌药之一——是一项重大成就，而莫德纳的疫苗做到了这一点。
None of this takes away from the science. Improving on Keytruda, one of the most effective cancer drugs ever made, is a major achievement, and Moderna’s shot did it.
从现在开始，该股票的走势将取决于接下来的进展。肾癌数据可能会在几个月内出炉，而膀胱癌试验的结果可能会在2027年公布。莫德纳还在肺癌领域测试该疫苗，这可能是一个更大的市场机遇。
From here, the stock will trade on what comes next. Kidney cancer data could arrive in a few months, while results from a bladder cancer trial could come in 2027. Moderna is also testing the vaccine in lung cancer, a potentially bigger opportunity.
该疫苗在黑色素瘤治疗中奏效了。而这只股票需要它在所有地方都奏效。
The vaccine works in melanoma. The stock needs it to work everywhere else.