GRAIL Q4 2025 业绩会问答中英对照
Operator
[Operator Instructions] Our first question will come from Subbu Nambi with Guggenheim.
[接线员说明] 第一个问题来自 Guggenheim 的 Subbu Nambi。
Subhalaxmi Nambi
Guggenheim Securities, LLC, Research Division
Can you confirm that you don't expect the FDA approval decision to be impacted by the miss of the stage shift endpoint? We know the FDA PMA package only included the prevalent screening round of NHS, but reasonably reviewers at the FDA will see this outcome, right?
能否确认你们不认为 FDA 的批准决定会因未达到分期转移终点而受到影响？我们知道 FDA 的 PMA 申报材料仅包含了 NHS 的普遍筛查轮次，但 FDA 的审评人员理应会看到这一试验结果，对吗？
Robert Ragusa
CEO & Director
Yes. Thanks for the question, Subbu. So as you know, the FDA will look at the effectiveness and safety of our submission. And so with the data that we have both from PATHFINDER 2 as well as the current -- the prevalent round of the NHS-Galleri, they'll be looking at that data. So there's not an obvious correlation or obvious impact between the final results of the NHS-Galleri study and the FDA's view on the test.
是的，谢谢你的提问，Subbu。如你所知，FDA 会关注我们申报材料的有效性和安全性。他们会审阅来自 PATHFINDER 2 以及 NHS-Galleri 当前普遍筛查轮次的数据。因此，NHS-Galleri 研究的最终结果与该试验对 FDA 关于此检测的看法之间并没有明显的相关性，也没有明显的影响。
Subhalaxmi Nambi
Guggenheim Securities, LLC, Research Division
And one follow-up. Is there any read-through from missing the NHS-Galleri stage shift endpoint to the Medicare REACH study, which has a primary endpoint of incidence rates of Stage IV cancers, right? And does that have any impact as Medicare -- as you look to getting some coverage?
还有一个后续问题。NHS-Galleri 未达到分期转移终点，这对 Medicare REACH 研究（其主要终点是 IV 期癌症发生率）是否有任何参考意义？这会对你们寻求 Medicare 覆盖产生影响吗？
Robert Ragusa
CEO & Director
Yes. Thanks again. Josh, do you want to take that?
好的，再次感谢。 Josh，你要回答这个问题吗？
Joshua Ofman
President
Sure. Yes. No, you're absolutely correct. So the primary endpoint of the REACH study is a Stage IV reduction, which is what was observed quite strongly in the NHS-Galleri trial. So I think the only read-through is that we believe it's critically important and clinically important to reduce the incidence of metastatic disease in Stage IV cancer, and that's a really important clinical endpoint, and we're looking forward to assessing that in the REACH trial.
当然可以。是的，你说得完全正确。REACH 研究的主要终点是IV 期癌症的减少，而这一点在 NHS-Galleri 试验中得到了相当明显的观察。所以我认为唯一的参考意义在于，我们坚信降低 IV 期转移性癌症的发生率在临床和实际上都至关重要，这是一个非常重要的临床终点，我们也期待在 REACH 试验中评估该指标。
Subhalaxmi Nambi
Guggenheim Securities, LLC, Research Division
And Josh, what if we don't reach the statistical significance there, would that have any impact? Or you're saying because it's 50,000, the study is not powered enough?
Josh，如果我们在该研究里没有达到统计显著性，会有影响吗？还是像你说的，因为样本量是 5 万人，研究效力不足？
Joshua Ofman
President
Yes. No, we believe the study is properly powered. It will have a control group, and we believe it is properly powered for that type of study, given the effect size that we know and the cancer detection rate that we're seeing. So we're very optimistic about observing that effect, but we need the study, obviously, to read out, and that's going to take some time.
是的，不，我们认为该研究具备足够的统计效力。它将设有对照组，并且基于我们已知的效果大小和观察到的癌症检出率，我们认为该研究的效力足以检测此类效应。所以我们对该效应的观察非常乐观，但显然需要等待研究数据读出，这需要一些时间。
Operator
Your next question will come from Kyle Mikson with Canaccord Genuity.
下一个问题来自 Canaccord Genuity 的 Kyle Mikson。
Kyle Mikson
Canaccord Genuity Corp., Research Division
Hopefully, you can hear me. I guess first one would be, how does the results here kind of impact your strategy to expand Galleri to other countries in terms of data generation and rollout plans? How would that differ now? And then maybe you could just touch on what are next steps in the U.K. Have you had any discussions with them so far? Or is that later on?
希望你们能听到我。我的第一个问题是，这里的结果会如何影响你们将 Galleri 推广到其他国家的策略，特别是在数据生成和推出计划方面？与之前相比会有什么不同？另外，能否谈一下你们在英国接下来的步骤？到目前为止是否与他们有过讨论，还是要等到之后？
Robert Ragusa
CEO & Director
Yes. Thanks for that, Kyle. So we do think as we outlined in the releases that strong reduction that we saw in Stage IV cancer, the fourfold improvement in cancer detection rate compared to standard of care, the absolute number of Stage I and II cancers increasing and the reduction in emergency presentation. We think all of those will be important as we go to other countries and the discussions with them. Obviously, other countries will -- each one will evaluate those elements independently. But we do think that's going to be a strong data set to go out there. So I think that's going to be very useful. Maybe I'll pass it over to Harpal to comment on the U.K. and the impact there.
好的，谢谢，Kyle。正如我们在新闻稿中所概述的，我们确实认为，IV 期癌症的大幅减少、相较于标准治疗的癌症检出率提升四倍、I 期和 II 期癌症绝对数量的增加，以及急诊途径发现癌症的减少——所有这些在我们进入其他国家并与它们讨论时都将是重要的因素。显然，每个国家都会独立评估这些因素。但我们相信这将是一套强有力的数据集，对外推广非常有用。或许我交给 Harpal 来评论英国的情况及其影响。
Harpal Kumar
Chief Scientific Officer & President International
Yes. Thanks, Bob. I mean just adding to what Bob said first, I mean, we think this is a really strong data set that demonstrates compelling clinical benefit. We know that there is now a growing arsenal of very effective treatments for many types of stage -- many types of cancer at Stage III. And so the potential benefits that we're talking about here from the NHS-Galleri study are going to be applicable worldwide. And so I don't think it has any -- certainly no negative bearing on our international approach. Indeed, I would hope it has a positive bearing on our international approach.
是的，谢谢，Bob。我先补充一下 Bob 所说的，我们认为这是一个非常强有力的数据集，展示了引人注目的临床益处。我们知道，目前针对许多 III 期癌症类型已有越来越多的高效治疗手段。因此，NHS-Galleri 研究所体现的潜在益处可以在全球范围内适用。所以我不认为这对我们的国际化战略有任何——当然更不会有负面影响。实际上，我希望它对我们的国际化战略产生积极影响。
So we feel really, really very pleased with the overall set of results. With respect to the U.K. specifically and the NHS, yes, look, we've just got these data. We haven't started having those conversations yet. My anticipation would be that they would want to see the full results before engaging in meaningful conversations, and we expect to have those at ASCO.
我们对整体结果感到非常满意。具体到英国和 NHS，的确，我们刚刚拿到这些数据，尚未开始正式讨论。我预计他们会希望在展开实质性对话前先看到完整结果，而我们预期这些结果会在 ASCO 上呈现。
Kyle Mikson
Canaccord Genuity Corp., Research Division
And then I hate to nittpick, but if you're expanding the sales force, if the results didn't meet the endpoint, I guess, like what's the thought process there. You're very bullish on the future here. I'm just curious what's driving that.
然后我不想吹毛求疵，但如果你们在扩大销售团队的同时，试验结果并未达到主要终点，我想知道你们的思路是什么。你们对未来非常看好，我只是好奇背后的驱动因素是什么。
Robert Ragusa
CEO & Director
Yes. So again, if you think about the things we saw in terms of reduction in Stage I and II, the -- excuse me, the increased Stage I and II cancers, and the reduction in Stage IV cancers, those are things that we've looked at within the U.S. that are very, very relevant to clinicians. And maybe to give a little more color, I'll pass it over to Andy, our Chief Commercial Officer.
是的，再说一次，如果你考虑我们看到的——抱歉，是 I 期和 II 期癌症的增加，以及 IV 期癌症的减少，这些是我们从美国市场角度看到的、与临床医生高度相关的结果。为了让解释更具体，我交给我们的首席商务官 Andy。
Andrew Partridge
Chief Commercial Officer
Yes. Thanks, Bob. Based on the market research studies that we've done and also consistent customer feedback that we've received from early adopting customers, the NHS-Galleri results that we've released today, we believe, based on everything we've heard and done will be both compelling and meaningful to our customers in terms of the magnitude of both the Stage IV reduction that we've disclosed and also the increased cancer detection rates of fourfold. And we believe that's going to increase both the depth and breadth of prescribing. Hence, we're expanding the provider sales force territories in the U.S.
是的，谢谢 Bob。根据我们开展的市场研究以及早期采用客户的一致反馈，我们今天发布的 NHS-Galleri 结果，基于我们听到的和所做的一切，我们相信在披露的 IV 期癌症降幅幅度以及四倍的癌症检出率提升方面，对客户而言既具说服力又有意义。我们认为这将增加处方的深度和广度，因此我们正在扩大美国面向医疗服务提供方的销售团队覆盖范围。
Operator
Your next question will come from Doug Schenkel with Wolfe Research.
下一个问题来自 Wolfe Research 的 Doug Schenkel。
Douglas Schenkel
Wolfe Research, LLC
I'll try to get them all out there upfront and then listen. So first, really a follow-up to the very first question, and I think it's the most important question tonight given the stock reaction in the aftermarket. So I want us to be airtight on this. Is the probability of FDA approval unchanged as a result of the NHS-Galleri readout? Because if the answer is, the probability is unchanged, it would mean the value associated with FDA approval and by extension, CMS reimbursement is also unchanged. So that's the first question. Yes or no, has the probability not changed?
我先一口气把问题都提出来再听回答。首先，这其实是第一个问题的后续，我认为鉴于盘后股价反应，这也是今晚最重要的问题。所以我们必须把这一点说得滴水不漏：NHS-Galleri 试验结果是否导致 FDA 批准的概率发生变化？因为如果答案是概率不变，那就意味着 FDA 批准以及延伸出的 CMS 报销的相关价值也不变。这是第一个问题，请直接回答是或否，概率是否没变？
The second question is on NHS coverage in the U.K. I know, again, you just got a question on this, but I'm curious if there are any examples you can point to where a diagnostic has been reimbursed after missing a primary endpoint. And then my third question is, has your analysis of NHS-Galleri results led you to any explanation regarding why you came up short of the primary endpoint? Are there potential design issues or population skews, anything like that?
第二个问题是关于英国的 NHS 覆盖。我知道你们刚回答过相关问题，但我很好奇，有没有案例是某诊断产品在错过主要终点后仍然获得报销的？第三个问题是，你们对 NHS-Galleri 结果的分析是否得出为何未能达到主要终点的解释？是否存在潜在设计问题或人群偏差等因素？
Robert Ragusa
CEO & Director
Yes. Thanks, Doug. Maybe, Josh, I'll hand over to the FDA questions to you.
好的，谢谢 Doug。或许 Josh，我把 FDA 相关的问题交给你。
Joshua Ofman
President
Yes. Thanks for the question, Doug. Everything we've learned from the FDA, their history with us, our conversations has been, their focus is going to be on clinical performance and safety. And the data set that we are -- that we have submitted includes the full PATHFINDER 2 study of the first 25,000 participants and the first year, which is the performance period of the NHS Galleri trial.
是的，谢谢你的提问，Doug。我们从 FDA 那里了解到的信息，包括双方的历史交流，都表明他们关注的是临床性能和安全性。我们提交的数据集包括 PATHFINDER 2 首批 25,000 名受试者的完整研究以及 NHS-Galleri 试验第一年的数据（即性能观察期）。
In their advisory board meetings and their public comments, they have been quite clear that their focus is on clinical validation and not clinical utility. And what we've tried to demonstrate in the NHS trial is a population level effect well beyond clinical validation and clinical performance. And we were able to demonstrate a really important finding of a substantial reduction in Stage IV cancers and a fourfold improvement in the cancer detection rate. But those are things that are not part of our submission right now to the FDA. And based on their own comments, they're going to be focused on clinical validation.
在他们的顾问委员会会议及公开声明中，他们已明确表示关注的是临床验证而非临床效用。我们在 NHS 试验中试图证明的是超越临床验证和性能的人群层面的效应。我们确实展示了 IV 期癌症大幅减少以及癌症检出率提升四倍的重要发现，但这些并不是我们目前向 FDA 提交材料的一部分。根据他们自己的说法，他们将专注于临床验证。
Robert Ragusa
CEO & Director
And maybe Harpal, you want to maybe just comment...
或许 Harpal，你想简单评论一下……
Harpal Kumar
Chief Scientific Officer & President International
So I think -- Doug, I think your second question was around endpoints on diagnostic studies. I think it's just worth pointing out that it's extremely rare for any diagnostic to go through a randomized controlled trial. It's very common for drugs to go through randomized controlled trials, but you actually very rarely see a diagnostic test evaluated in as rigorous a way as we have done through the NHS-Galleri trial. I just think it's really important to make that point.
我觉得——Doug，你的第二个问题是关于诊断研究的终点。我想指出的是，任何诊断产品极少会经过随机对照试验。药物做随机对照试验很常见，但诊断检测很少像我们在 NHS-Galleri 试验中这样接受如此严格的评估。我认为强调这一点很重要。
Not only have we rigorously assessed it through an RCT, but it's enormously large trial, 142,000 people. So we have a data set the likes of which I am not aware any other diagnostic has been through other than sort of really significant interventional diagnostic type products. So I think that's the first thing to say.
我们不仅通过 RCT 进行了严格评估，而且这是一项规模巨大的试验，涉及 142,000 人。因此，我们所拥有的数据集在已知案例中独一无二，除了某些重大的介入性诊断产品外，没有其他诊断检测经历过类似过程。这是我想说的第一点。
The second thing to say is this is an enormously rich data set, and it has a large number of components to it, and we've shared those with you today. It's absolutely right to say we didn't hit the primary endpoint. But what we did see was a very compelling clinical benefit here. And I think that story stands in terms of generating excitement out there in the clinical community around what's possible with a test like this. Being able to reduce Stage IV cancers gives clinicians the opportunity to use curative treatments that they otherwise wouldn't have the opportunity to use. So I think that's really very compelling.
第二，这是一个极其丰富的数据集，包含大量组成部分，我们今天已向各位分享。诚然我们没有达到主要终点，但我们确实看到了非常有说服力的临床益处。我认为这个故事能在临床界引发对这类检测潜力的热情。能够减少 IV 期癌症，让临床医生有机会使用原本无法使用的根治性治疗方案，这点非常具有吸引力。
And then your third question, I think, was about what are we learning looking at the data. And just a couple of comments on that. First of all, it's -- we've not had this data for very long. We're looking into it. There's a lot of data to work through. One of the things we've seen is that -- and if I break apart the primary endpoint, it's a combined Stage III and IV reduction. And so when you break that apart, we did see a Stage IV reduction. But as we've commented on, we saw an increase in Stage II cancers.
你的第三个问题是关于我们从数据中得出的分析。我只想说几点：首先，我们获得这些数据的时间不长，仍在深入分析，数据量庞大。我们注意到——如果把主要终点拆分为 III 期和 IV 期合计减少，分开看的话，我们确实看到 IV 期减少；但正如我们之前提到的，II 期癌症有所增加。
And one of the things that looks to be the case when we look at the data is that we expect to see a stronger effect if we were to continue to follow up this cohort for a longer period of time. And that's why we're saying we want to extend the follow-up for a further 6 to 12 months, and that's why we'll be doing that. So that's one of the things that we've seen when we're looking at the data, but there's a lot more to learn.
从数据来看，一个可能的结论是，如果我们对这一队列进行更长时间的随访，可能会看到更强的效应。这也是为什么我们说要将随访期再延长 6 至 12 个月，并确实会这样做。这是我们目前从数据中看到的一点，但还有更多有待探索。
Douglas Schenkel
Wolfe Research, LLC
Thanks, Harpal. That’s helpful. Just a quick clarification — when you mentioned extending follow‑up by 6 to 12 months, is that only for the NHS‑Galleri cohort, or are you considering extending PATHFINDER2 as well?
谢谢，Harpal，很有帮助。我快速确认一下——你提到将随访期延长 6 至 12 个月，这是仅针对 NHS‑Galleri 队列，还是也在考虑延长 PATHFINDER2？
Harpal Kumar
Chief Scientific Officer & President International
That’s a great question. At this point, the extension applies specifically to the NHS‑Galleri cohort. PATHFINDER2 is essentially complete in terms of its follow‑up period for the data we have analyzed so far. The reason for extending NHS‑Galleri is the observation of the higher‑than‑expected StageII incidence and the potential for a stronger effect with longer observation, as I mentioned earlier. We don’t have plans at this stage to extend PATHFINDER2, but we will continue to monitor those data closely.
这是个很好的问题。目前，延长的计划仅适用于 NHS‑Galleri 队列。PATHFINDER2 在我们目前已分析的数据方面，随访期基本已经完成。延长 NHS‑Galleri 的原因是我刚才提到的——II 期癌症发生率高于预期，以及延长观察可能显现更强效应。现阶段我们没有延长 PATHFINDER2 的计划，但会继续密切监测那些数据。
Operator
Your next question will come from Prakash Chari with SVB Leerink.
下一个问题来自 SVB Leerink 的 Prakash Chari。
Prakash Chari
SVB Leerink LLC, Research Division
Congratulations on the results. Two questions, if I may. First, can you elaborate on the operational impact of the Medicare coverage law? Will it immediately allow billing for Galleri under Medicare, or is there still a requirement to wait for FDA approval plus local coverage determination? And second, any update on the timeline for CMS to establish a specific coverage pathway under the new law?
祝贺你们取得结果。如果可以，我有两个问题。第一，能否详细说明《Medicare 覆盖法案》的运营影响？它会立即允许在 Medicare 下对 Galleri 进行收费，还是仍需等待 FDA 批准以及地方覆盖决定？第二，CMS 在新法下建立具体覆盖路径的时间表是否有更新？
Robert Ragusa
CEO & Director
Thanks, Prakash. Great questions. On the Medicare law itself, it establishes a pathway — meaning it creates the legislative framework for CMS to develop a national coverage determination for FDA‑approved MCED tests. However, it does not mean immediate billing eligibility. We still must receive FDA approval for Galleri, and then CMS would undertake its own evidence review and issue a coverage determination. So there will be that stepwise process.
谢谢，Prakash，非常好的问题。关于 Medicare 法案本身，它建立了一个路径——也就是说，它为 CMS 制定 FDA 批准的 MCED 检测全国覆盖决定创建了立法框架。但这并不意味著可以立即收费。我们仍需获得 Galleri 的 FDA 批准，然后 CMS 才会进行独立的证据审评并发布覆盖决定。所以会有一个逐步推进的过程。
Joshua Ofman
President
Yes, and to add to that — the law requires CMS to initiate a coverage process within a “reasonable” timeframe once a test receives FDA approval, but it doesn’t specify an exact deadline. Historically, CMS national coverage determinations have taken anywhere from several months to over a year, depending on complexity and evidence requirements. We anticipate working closely with CMS during that period to ensure timely and appropriate evaluation.
是的，我再补充一点——该法律要求 CMS 在检测获得 FDA 批准后，在“合理”时间内启动覆盖程序，但并未规定确切截止日期。从历史上看，CMS 的全国覆盖决定耗时从几个月到一年多不等，取决于复杂性和证据要求。我们预计在此期间会与 CMS 紧密合作，以确保及时、恰当的审评。
Prakash Chari
SVB Leerink LLC, Research Division
Understood. Thank you. And just to clarify — once FDA approved and CMS issues a coverage policy, would reimbursement be at standard Medicare rates for lab tests, or is there a possibility of negotiated or value‑based rates?
明白了，谢谢。再确认一下——一旦 FDA 批准并且 CMS 发布覆盖政策，报销是按照实验室检测的标准 Medicare 费率，还是有可能采用协商费率或基于价值的付费方式？
Robert Ragusa
CEO & Director
Great question. The law specifies that CMS shall determine coverage and payment under existing Medicare payment systems unless a separate pathway is established. Initially, that means standard laboratory test rates are the baseline. However, there is precedent for CMS to create alternative payment models or negotiate rates for innovative diagnostics, especially where clinical and economic value is demonstrated. We will advocate for a model that reflects the public health benefit shown in our data.
问得好。法律规定，除非另行建立路径，否则 CMS 应在现有 Medicare 支付体系下确定覆盖和付费。这意味着初期会以标准实验室检测费率为基准。不过，在有先例的情况下，CMS 可为创新型诊断创建替代支付模式或进行费率谈判，尤其是当临床和经济价值得到证实之时。我们将倡导一种能反映我们数据中体现的公共卫生效益的模式。
Operator
Your next question will come from Elizabeth Krueger with Morgan Stanley.
下一个问题来自 Morgan Stanley 的 Elizabeth Krueger。
Elizabeth Krueger
Morgan Stanley & Co. LLC, Research Division
Thanks for taking my question. I wanted to ask about the discounting programs you referenced in the prepared remarks. Could you quantify the impact on revenue per test versus list price, and whether this pricing strategy is sustainable as you scale? Also, any concern about margin dilution as you expand access?
谢谢你们回答我的问题。我想问一下在准备发言中提到的折扣计划。能否量化其对单次检测收入相对于标价的影响？这种定价策略在规模化后是否可持续？另外，在扩大可及性方面，是否担心利润率被稀释？
Aaron Freidin
Chief Financial Officer
Yes, thanks, Elizabeth. Good question. Our discounting programs vary by customer segment and volume tier. On average, we’re seeing discounts in the range of 15% to 25% off list price, which translates to roughly a
75to75 to 75to
125 reduction per test depending on the contracted list price point. This has enabled us to bring new prescribers into the system and expand access, particularly in the self‑pay market.
是的，谢谢，Elizabeth，好问题。我们的折扣计划因客户细分和采购量层级而异。平均来看，我们看到相对标价的折扣幅度在 15% 至 25% 之间，按合同标价计算，相当于每次检测降价约 75 至 125 美元。这使我们能够将新的处方医生引入系统并扩大可及性，尤其在自费市场中效果明显。
In terms of sustainability, we believe it is sustainable in the near term while we build volume and physician familiarity. Over time, as utilization scales and our cost per test declines through efficiencies, we aim to moderate discount levels without compromising access. Regarding margin dilution, we monitor this closely; the increase in volume efficiencies and mix toward higher‑margin screening revenue helps offset the initial discount impact.
可持续性方面，我们认为在短期内建立销量和提升医生熟悉度的阶段是可维持的。长远来看，随著使用量增加以及通过效率提升降低单次检测成本，我们计划在不影响可及性的前提下适度降低折扣力度。关于利润率稀释，我们对此密切监控；销量效率提升以及收入结构向更高利润率的筛查收入倾斜，有助于抵消初期的折扣影响。
Elizabeth Krueger
Morgan Stanley & Co. LLC, Research Division
Got it. And just to clarify — the
75to75 to 75to
125 reduction is per test relative to list?
明白了。再确认一下——75 至 125 美元的降幅是指每次检测相对于标价吗？
Aaron Freidin
Chief Financial Officer
Correct — that’s the per‑test reduction range from list price under our current discount structures.
没错——这是在当前折扣结构下，每次检测相对于标价的降价区间。