Almost 15 years ago, in the midst of an opioid epidemic that would kill more than half a million people in the U.S., a startup formed with the aim of creating new, non-addictive pain drugs.

大约15年前，在阿片类药物流行期间，美国将有50多万人死亡，成立了一家旨在开发新型非成瘾止痛药的初创公司。

This goal could have been seen as noble. But for most investors, it was far too risky. Pain research was known to be exceedingly difficult and, even if successful, any resulting products would have to compete in a healthcare system that opioid makers had already gamed.

这个目标本可以被视为崇高。但对大多数投资者来说，风险太大了。众所周知，疼痛研究非常困难，即使成功，任何产生的产品都必须在阿片类药物制造商已经玩过的医疗保健系统中竞争。

The startup, SiteOne Therapeutics, has stayed afloat in the years since mostly through small grant funds. Yet, in a major reversal of fortune, it recently began to receive a huge influx of investment. The company on Wednesday announced the closing of a $100 million fundraising round, and plans to put the cash toward human studies designed to show its drugs work as intended..

这家初创公司SiteOne Therapeutics在此后的几年中一直保持着良好的发展势头，主要是通过小额赠款。然而，在一次重大的财富逆转中，它最近开始获得大量投资。该公司周三宣布结束一轮1亿美元的筹资活动，并计划将资金用于人体研究，以证明其药物的预期效果。。

“Pain has really been out of favor in the industry up until very recently,” said John Mulcahy, SiteOne’s cofounder and CEO. “Now is the time to add additional resources to really ramp things up.”

SiteOne的联合创始人兼首席执行官约翰·穆尔卡希（JohnMulcahy）表示：“直到最近，疼痛在业界还真的不受欢迎。”。“现在是时候添加额外资源以真正提高产量了。”

SiteOne’s research focuses on a kind of protein that’s embedded, by the thousands, in the perimeter of cells. Aptly named “ion channels,” these microscopic tunnels allow cells to communicate with one another through the rush of electrically charged particles. They are essential. Without them, our bodies wouldn’t be able to move muscles, sense surroundings or fight against germs..

SiteOne的研究集中在一种蛋白质上，这种蛋白质成千上万地嵌入细胞周围。这些微小的隧道被恰当地命名为“离子通道”，使细胞能够通过带电粒子的冲击相互通信。它们是必不可少的。没有它们，我们的身体将无法移动肌肉，感知周围环境或对抗细菌。。

These functions also make ion channels attractive targets for drug researchers, who have already found ways to use them to combat seizures, infections, and problems with the heart and blood pressure. And over the past couple decades, technological advances have led to a better understanding of these proteins, such that some pharmaceutical companies now believe the field will, before too long, produce new treatments for pain, epilepsy, depression and many more neurological conditions..

这些功能也使离子通道成为药物研究人员的诱人目标，他们已经找到了使用离子通道来对抗癫痫发作、感染以及心脏和血压问题的方法。在过去的几十年中，技术进步使人们对这些蛋白质有了更好的理解，因此一些制药公司现在相信，不久之后，该领域将为疼痛、癫痫、抑郁症和更多神经系统疾病提供新的治疗方法。。

Vertex Pharmaceuticals, which is currently worth more than $120 billion, proved how valuable this research can be through a series of drugs that transformed cystic fibrosis treatment by improving the function of chloride ion channels.

Vertex Pharmaceuticals目前价值超过1200亿美元，通过一系列通过改善氯离子通道功能来改变囊性纤维化治疗的药物，证明了这项研究的价值。

The Boston-based biotechnology company also spent years developing its own non-opioid pain medication. The drug acts on “NaV1.8” — one of the nine known types of sodium channels — and has demonstrated in a few medium to large clinical trials the ability to significantly reduce multiple kinds of pain, from chronic nerve pain to acute pain.

这家总部位于波士顿的生物技术公司也花了数年时间开发了自己的非阿片类止痛药。该药物作用于九种已知钠通道之一的“NaV1.8”，并在一些中大型临床试验中证明了其能够显着减轻多种疼痛，从慢性神经疼痛到急性疼痛。

Vertex this spring asked for approval in the acute setting, and analysts expect the Food and Drug Administration to oblige before the end of January..

。。

SiteOne has a complicated relationship with Vertex. Its lead program also regulates NaV1.8, meaning the companies may one day be competitors. Yet they are also working together on a different non-opioid pain drug that targets the “NaV1.7” sodium channel.

SiteOne与顶点有着复杂的关系。其领先项目还监管NaV1.8，这意味着这些公司有朝一日可能成为竞争对手。然而，他们也在合作开发另一种针对“NaV1.7”钠通道的非阿片类止痛药。

More broadly, Vertex exerts an almost gravitational force on SiteOne. How the former moves through testing and, potentially, selling its pain drug directly affects the latter. This dynamic played out in SiteOne’s latest funding round, which was led by Novo Holdings, the controlling stakeholder of Ozempic-maker Novo Nordisk..

更广泛地说，顶点在SiteOne上施加几乎重力。。这一动态在SiteOne的最新一轮融资中得到了体现，该轮融资由Ozempic制造商诺和诺德的控股股东诺和诺德控股牵头。。

According to Ken Harrison, a senior partner at Novo Holdings, the firm had kept an eye on SiteOne pretty much since it formed in 2010. After years of waiting, the firm finally decided to invest late last year, partially because of promising early data from SiteOne, but also because Vertex had established a pathway to successfully develop these kinds of drugs..

据诺沃控股公司（Novo Holdings）高级合伙人肯·哈里森（KenHarrison）表示，该公司自2010年成立以来，一直在密切关注SiteOne。。。

“The Vertex data were very compelling … multibillions in market cap were added in a single day when they press released their Phase 2 and Phase 3 data sets,” Harrison said. “If the Vertex data did not exist, would we have invested? I don't know, actually.”

哈里森说：“Vertex的数据非常令人信服……当他们发布第二阶段和第三阶段的数据集时，一天之内市值就增加了数十亿美元。”。“如果顶点数据不存在，我们会投资吗？实际上我不知道。”

Harrison added that, having been in contact for years, Novo Holdings was impressed by the SiteOne team’s candor and scientific rigor. “They would only put something in the clinic that they thought was worth it,” he said. “That means a lot, that sort of truth-seeking behavior.”

哈里森补充说，经过多年的接触，Novo Holdings对SiteOne团队的坦率和科学严谨印象深刻。他说：“他们只会在诊所放一些他们认为值得的东西。”。“这意味着很多，那种寻求真相的行为。”

The firm naturally still did due diligence. It searched around for other companies developing NaV1.8 drugs and found sparse pickings. It also weighed the potential commercial challenges. SiteOne would have to contend not only with a large, deep-pocketed rival in Vertex, but a market where inexpensive opioids are favored by insurers and remain entrenched in certain pain treatment plans..

该公司自然仍在进行尽职调查。它四处搜索其他开发NaV1.8药物的公司，发现很少有人挑选。它还权衡了潜在的商业挑战。SiteOne不仅要与Vertex的一个财大气粗的竞争对手竞争，还要与一个廉价阿片类药物受到保险公司青睐并在某些疼痛治疗计划中根深蒂固的市场竞争。。

The few payers Novo Holdings has spoken to understand the problems with opioids and the need for new, non-addictive pain medications, according to Harrison. “But when it comes to pricing and the market realities payers will face with these drugs coming out, honestly I don't know,” he said. “Commercially, Vertex is going to pave the way here for everyone.”.

哈里森表示，Novo Holdings的少数付款人已经表示了解阿片类药物的问题以及对新型非成瘾止痛药的需求。“但是，当涉及到定价和市场现实时，付款人将面临这些药物的上市，老实说，我不知道，”他说。。

SiteOne Therapeutics CEO John Mulcahy

SiteOne Therapeutics首席执行官John Mulcahy

Permission granted by SiteOne Therapeutics

SiteOne Therapeutics授予的许可

SiteOne’s new funding round also saw participation from OrbiMed, Wellington Management, Mission BioCapital and BSquared Capital, as well as existing investors. The company previously raised $15 million in 2017 through a Series B round led by Amgen. The two drugmakers had partnered on SiteOne’s NaV1.7 program, but that agreement fizzled in late 2019 when Amgen exited neuroscience research..

SiteOne的新一轮融资也吸引了OrbiMed、惠灵顿管理、Mission BioCapital和BSquared Capital以及现有投资者的参与。该公司之前在2017年通过安进牵头的B轮融资筹集了1500万美元。这两家制药商曾在SiteOne的NaV1.7项目上合作，但该协议在2019年末因安进退出神经科学研究而宣告失败。。

SiteOne expects the latest haul to get it through “proof-of-concept” studies in both acute and chronic pain. A Phase 1 trial evaluating its lead drug in healthy volunteers kicked off in the middle of this year, and should produce data before the end of March. Mulcahy said data from acute pain testing should come in the first quarter of 2026, whereas the chronic pain work will “take a bit longer.”.

SiteOne预计最新成果将通过急性和慢性疼痛的“概念验证”研究。一项在健康志愿者中评估其先导药物的第一阶段试验于今年年中启动，并应在3月底之前产生数据。穆尔卡希说，急性疼痛测试的数据应该在2026年第一季度发布，而慢性疼痛的工作“需要更长的时间”。

Like Vertex, SiteOne intends to show its drug can treat acute pain first by assessing it in people who just underwent either a “tummy tuck” surgery or a bunionectomy. The company hasn’t fully decided where to begin in chronic pain, Mulcahy said, though diabetic neuropathy would be “the most logical place to start.”.

和Vertex一样，SiteOne打算首先通过对刚刚接受“腹部手术”或膀胱切除术的患者进行评估来证明其药物可以治疗急性疼痛。。

Harrison notes that, historically, venture capitalists viewed chronic pain as a more rewarding indication. “That is likely still the case,” he said, “but this is a very unique time to be thinking about the acute pain market as well, because of the recognition across the board, especially with physicians, that non-opioid alternatives are needed and we don't have enough [research] activity.”.

哈里森指出，从历史上看，风险资本家将慢性疼痛视为一种更有益的迹象。“情况可能仍然如此，”他说，“但这也是思考急性疼痛市场的一个非常独特的时刻，因为人们普遍认识到，特别是医生，需要非阿片类药物替代品，而我们没有足够的[研究]活动。”。

SiteOne isn’t alone in chasing Vertex. Latigo Therapeutics, a California-based biotech created by the venture firm Westlake Partners, is developing a NaV1.8 therapy directed at acute and chronic pain. Latigo debuted in February, equipped with $135 million in funding and some of the scientists who were laid off when Amgen left brain drugs behind..

SiteOne并不是唯一一个追逐Vertex的公司。Latigo Therapeutics是一家总部位于加利福尼亚州的生物技术公司，由风险投资公司Westlake Partners创建，目前正在开发一种针对急性和慢性疼痛的NaV1.8疗法。Latigo于2月首次亮相，获得了1.35亿美元的资金，以及安进公司留下脑部药物后被解雇的一些科学家。。

“Novo’s investment thesis is that this is perhaps a horse race with two or three competitors, but one in which every horse can win,” Harrison said.

哈里森说：“诺沃的投资论点是，这可能是一场有两到三名竞争者的赛马，但每匹马都能获胜。”。