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Good day, ladies and gentlemen, welcome to the GRAIL First Quarter 2026 earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. Please be advised that this conference call is being recorded. GRAIL Investor Relations, please begin.

Thank you, and thank you all for joining us today. On the call are Bob Ragusa, our Chief Executive Officer, Aaron Frieden, our Chief Financial Officer, Josh Ofman, President, Harpal Kumar, Chief Scientific Officer and President International, and Andy Partridge, Chief Commercial Officer. I'll remind you that we'll be making forward-looking statements based on current expectations. It's our intent that all statements other than statements of historical fact, including statements regarding our anticipated financial results and commercial activity, will be covered by the safe harbor provisions for forward-looking statements under Federal Securities laws. Forward-looking statements are subject to risks and uncertainties. Actual events or results may differ materially from those projected or discussed. All forward-looking statements are based upon currently available information, and GRAIL assumes no obligation to update these statements.

To better understand the risks and uncertainties that could cause actual results to differ, we refer you to the documents that GRAIL files with the SEC, including the Risk Factor section on GRAIL's most recent annual report on Form 10-K and the quarterly report on Form 10-Q, which we plan to file for the 1st quarter of 2026. This call will also include a discussion of GAAP results and certain non-GAAP financial measures, including adjusted gross profit and adjusted EBITDA, which excludes certain specified items. Our non-GAAP financial measures are intended to supplement your understanding of GRAIL's financials. Reconciliations of the non-GAAP measures to most directly comparable GAAP financial measures are available in the press release issued today, which is posted to our website. With that, we turn to Bob.

Good afternoon, everyone, and thank you for joining us to review first quarter results. I will take a moment to highlight recent achievements before turning it over to Josh for an update on our clinical programs and recent and upcoming data, then over to Aaron to cover financials. This quarter, we saw continued strong commercial momentum with expanding physician adoption, increasing engagement across health systems, and growth in test volumes. GRAIL sold over 56,000 Galleri tests in the first quarter, a 50% increase in volume year-over-year. Total Galleri screening revenue was $39.8 million, up 37% over the prior year. We are making important strides to enhance provider and patient awareness of MCED. We continue to grow our partnerships with health systems, which educate physicians and engage the community.

We are seeing growing deployment of Galleri in leading systems, including Dana-Farber, Rush, OHSU, and Cleveland Clinic and Duke. We are seeing major health systems, including Community Health and Intermountain, investing in new and expanded employee benefit coverage of Galleri. We are continuing to deepen our work with existing digital health partners, which enable outreach to curated memberships. We have also recently added additional partners such as WHOOP. Also, our employer relationships continue to expand as experience with Galleri grows. We've invested in the ease of access through our previously announced partnership with Quest to integrate into their ordering systems and our recently announced collaboration with the Epic electronic health record platform.

Integration through Epic Aura will allow health systems and their HCPs to order the Galleri test directly at the point of care, receive structured results, and manage patient follow-up within their existing native EHR and with their existing clinical workflows. Integration will provide standardized implementation and quicker onboarding for health systems adopting Galleri. Integrations are beginning now. In January, we announced that we completed our FDA PMA submission, which has been accepted by the FDA for review. The PMA for Galleri is focused on test performance and safety results from the first approximately 25,000 participants in the PATHFINDER 2 study with 1-year follow-up and the prevalent screening round only of the NHS-Galleri trial. The submission also includes a bridging analysis to compare performance of the version Galleri used in the clinical trials to the updated version that has been submitted to the FDA for pre-market approval.

We announced in February our planned expansion of the field sales and medical teams. We expect the majority of the new sales personnel will be onboarded and trained by mid-year. We believe this expansion will enable us to continue to drive commercial momentum. Finally, we're looking forward to the upcoming data presentations for a 140,000 participant NHS-Galleri trial and the 35,000 participant PATHFINDER 2 study at the 2026 American Society of Clinical Oncology annual meeting later this month. We're excited to share data from the studies and begin to incorporate the learnings in our educational and sales initiatives. Following our data presentations at ASCO, we are planning to hold an analyst call on Sunday evening, May 31st. Stay tuned for details on the analyst call in the coming weeks. With that, I'll ask Joshua Ofman to provide an update on our clinical programs.

Thanks, Bob. At GRAIL, we're very excited about the comprehensive data we've been generating to demonstrate the value proposition for Galleri. This technology has been validated through robust studies, including those in intended use populations. More than 174,000 individuals are included in studies supporting our PMA submission to the FDA. We're seeing consistent results through hundreds of thousands of commercial and clinical study tests. Through our studies and commercial testing, we've built what we believe is the largest linked clinical and genomic data set in the field. We've already been able to use these data to drive test improvements and will continue to do that over time. Our teams have continued to present evidence demonstrating Galleri's performance at renowned medical conferences, including 2 new analyses at the American Association for Cancer Research annual meeting in April.

The first assessed the association between emergency department involvement in the diagnosis of cancer and overall survival across different cancer types in the Medicare population. Emergency department involvement was associated with a significant fraction of overall mortality in patients with cancer. Emergency department involvement in diagnosis remained a strong independent predictor of mortality after adjusting for sociodemographics, comorbidities, and stage of diagnosis. A second study evaluated adherence to mammography screening before and after MCED testing. Women who received a negative MCED result maintained their high adherence to guideline-recommended mammography, with greater than 80% undergoing screening in the 24 months after MCED testing. Similar rates in the 24 months before testing. As a reminder, Galleri is intended to be used alongside existing standard of care single cancer screening tests, and these findings suggest that MCED testing will not negatively impact participation in guideline-recommended cancer screening.

Earlier this year, we released top-line data from the NHS-Galleri trial, which is the first randomized trial to demonstrate population-scale stage shift for a Multi-Cancer Early Detection test. Working with the NHS, we agreed to a combined endpoint of stage 3 and 4 reduction over three rounds of screening. What was observed in the trial was an increase in stage 3 cancers detected and a decrease in stage 4 cancers detected, which ended up canceling one another out in this combined endpoint. While we did not achieve a statistically significant reduction in this combined primary endpoint, we did demonstrate a number of strong clinical utility findings. We observed an increase in the detection of stage 1 and 2 deadly cancers and a 4-fold higher cancer detection rate compared to standard of care screening alone.

These findings indicate we were able to find deadly cancers that we are not screening for and also find cancers that we've been missing with standard of care screening. We also observed meaningful reductions in stage 4 cancer diagnoses and in the emergency presentation of cancer. These findings suggest that with multiple rounds of screening, we may be able to identify some of the most lethal cancers earlier. Reducing stage 4 diagnoses is incredibly meaningful because there is a large survival cliff between stage 3 and stage 4 for many types of cancer. Many stage 3 cancers can now be treated with curative intent, and finding these cancers at stage 3 rather than stage 4 can make a meaningful difference in a patient's treatment experience and outcomes. The reduction in emergency presentation reflects a similar opportunity to improve the patient experience, their care, and their outcomes.

Cancers presenting in the emergency room represent 20% of cancer diagnosis in the U.K. and similar numbers in the U.S., and these cases are among the costliest and those associated with some of the poorest outcomes. We believe that both the increase in overall and in early cancer detection and the decrease in metastatic and emergency presentation of cancer are important and relevant to providers and payers in evaluating the clinical and economic value of Galleri as a complement to standard of care screening. We're really looking forward to presenting these data, plus the results from all 35,000 participants from our PATHFINDER 2 study at ASCO in just a few weeks. I'll hand off now to Aaron for a review of our financials.

Thanks, Josh, and good afternoon, everyone. I'm pleased to present our results for the first quarter. First quarter results were strong, with revenue of $40.8 million, up $8.9 million or 28% as compared to the first quarter of 2025. Total revenue for the quarter consisted of $39.8 million of screening revenue and $1 million of development service revenue. Screening revenues was up 37% as compared with the first quarter of 2025, with test volumes of more than 56,000 tests, an increase of 50% over Q1 of last year. Net loss for the quarter was $93.2 million, an improvement of 12% as compared to the first quarter of 2025.

Non-GAAP adjusted gross profit for the first quarter of 2026 was $19.7 million, an increase of $5.4 million or 38% as compared with the first quarter of 2025. Primary drivers of the increased gross margin were improved fixed cost leverage due to the increase in volumes and a decrease in sample reprocessing costs, partially offset by a decrease in ASP. Adjusted EBITDA for the first quarter of 2026 was negative $79.9 million, representing an improvement of $18.8 million or 19% as compared to the first quarter of 2025.

We ended the quarter with a cash position of $823.1 million, providing us with the financial flexibility to navigate growth over the next several years as we pursue key milestones toward broad access to our multi-cancer early detection technology. Back to you, Josh.

Thanks, Aaron. Bob, before your retirement at the end of this month, I want to take a moment to acknowledge the tremendous contributions you've made as CEO of GRAIL. All of us at GRAIL and everyone joining today's call who follows our story can appreciate the incredible progress you've led our teams through over the last 5 years. Our spin-out from Illumina, our commercial expansion, the scaling of our N.C. laboratory operations. As a result, GRAIL has a strong operational and financial foundation to advance Multi-Cancer Early Detection at scale and is well-positioned for long-term growth. Bob, on behalf of all of our teams at GRAIL, thank you.

Thanks very much, Josh. Leading GRAIL and working alongside this extraordinary team has been the greatest honor of my four decades in healthcare. We are addressing one of the most urgent healthcare challenges of our time, and I am extremely proud of our pioneering work. I'd also like to express my sincere thanks to each GRAIL employee. Every achievement we've made has been a result of the ideas and actions spurred by the great people across this company and driven by a commitment to a singular goal. Our vision is population scale, multi-cancer early detection, and we're making real advances each year. I'm pleased to pass the reins shortly to Josh, who's played a central role in driving GRAIL's strategy and execution over the past seven years. Operator, we can go to Q&A.

Thank you. At this time, if you would like to ask a question, please click on the Raise Hand button, which can be found on the black bar at the bottom of your screen. You may remove yourself from the queue at any time by lowering your hand. When it is your turn, you will hear your name called and receive a prompt to unmute. As a reminder, we are allowing analysts one question and one relevant follow-up today. We will wait one moment to allow the queue to form. Thank you. Our first question will come from Subbu Nambi with Guggenheim. Your line is open. Please ask your question.

Thank you for taking my question, great print. The FDA and CMS recently established their rapid pathway in which CMS will propose the NCD for Class 2, 3 breakthrough devices on the same day that the FDA provides market authorization. Given Galleri has the breakthrough device status and would be expected to be a Class 3 device, do you expect Galleri to be eligible for the rapid pathway, or does the 2029 start date specified in the NSAID bill negate this opportunity? Sorry for the long question.

Thanks, Subbu, for the question. You know, we've looked at rapid, right now it's kind of just a framework without a lot, you know, a lot of detail. You know, at a high level, it does look like, you know, the characteristics of our tests, you know, breakthrough designation, the fact that we're driving for FDA approval, does put us, you know, in what the act is intended for. We're hopeful that, you know, when the details come out, we will, you know, find ourselves, you know, being, you know, very much eligible for that. We do have to wait to see how the details unfold for that particular piece of legislation. Josh, I don't know, any other comments on that?

No, I mean, it's an important piece of regulation, and it's very encouraging. I mean, I think for years now, the government has been trying to shorten the gap between FDA approval and CMS coverage. This is something the administration has been prioritizing. It's great to see. I think to Bob's earlier point, everything that we've done from, you know, seeking FDA approval, having a breakthrough device designation, conducting an IDE that was reviewed by the FDA and CMS, should comport with what this regulation is intending to do. We're looking forward to seeing the details and the regulation itself.

Perfect. How much growth from partnerships like Function Health and Hims & Hers are factored in your guidance for Galleri growth in 2026? Maybe I missed this, but given the beat, are you raising guidance? I'm hopping through multiple earnings, so pardon my question here.

Aaron, you wanna take that one?

Yeah. Your first question, Subbu, nice to talk to you. You know, we've got our guidance, which, you know, we're reiterating still the same guidance, not updating it. You got a 10% range there. You know, one of the reasons for that is to really learn and see how the uptake works in the digital health space. Some of those partners like Function we've got more experience with. You know, with Hims & Hers and some of these other new agreements that we've signed, you know, as they implement, we'll see what uptake is like. You know, depending on how they implement it can go quickly, sometimes it doesn't.

Got it. Thank you so much, guys.

Your next question will come from Kyle Mikson with Canaccord Genuity. Please unmute your audio and ask your question.

Hey, guys. Thanks for the questions after addressing the quarter. First one, just a bigger picture question. It's been a few months since the NHS-Galleri reveal. Can you talk about the feedback from stakeholders since then? You know, very exciting to have the ASCO, you know, presentations pretty soon here. Do you expect to have a material change in opinions following those abstracts and perhaps the call with the investors as well?

Sure. First piece on the NHS. We obviously, you know, we had a strong quarter. We were able to grow volumes by 50% and revenues by 37% in the screening part of the business. You know, we clearly saw a current strength. Andy, maybe, you know, jump over to you to talk about, you know, the customer response to the NHS Galleri.

Yeah. Thanks, Bob. Thanks for the question. As Bob said, we've seen strong growth through Q1, kind of year-over-year, and that growth's been across brick-and-mortar providers, digital health, and employers. Drilling specifically into healthcare providers, we've seen a significant expansion of new ordering healthcare providers in Q1 with about 1,300 new prescribers to Galleri that we saw in the quarter. We've also added important new customers across our employer business, health systems, as Bob mentioned, you know, Cleveland Clinic, Duke, OHSU, all kind of came on board to incorporate Galleri with agreements in Q1, and also added new digital health customers in Q1. All of this in the midst of the NHS-Galleri data being released.

I think specifically to the NHS-Galleri data, that media coverage and some of the negative media coverage that was generated has led to questions from customers, you know, healthcare providers, employers, and also from patients. As the data from the study has not yet been presented, it's been difficult for our teams to answer every single patient or provider question related to the study. Therefore, once the data comes out at ASCO, there's definitely gonna be interest from customers for us to walk them through that detailed data, and we've got plans to train all of our sales force immediately after ASCO on that data so they can follow up with customers. As Aaron highlighted, we're confident in our growth prospects, and indeed we're finalizing our sales force expansion efforts.

Yeah. Wow, that was great. Thanks, guys, so much. I guess my final question or second question is gonna be about expansion opportunities, kind of in the near term here. You got the Epic EHR integration. I think planning for that began when that was basically announced in April or so. I know you have the Quest portal, you have Athena. Like, based on your experience with those platforms in the last year or so, you know, can you just talk about your enthusiasm of what Epic could do for you? You know, expansion plans to Oracle, Cerner, things like that.

Just on the Salesforce expansion as well, I mean, are you looking at, like, pretty healthy tailwinds in second half due to things like, you know, Epic and Salesforce expansion as well?

Yeah. If you think about, maybe cover the first part, you know, the Epic expansion, that's something we've been looking to do for a period of time. We're really excited about announcing that. We know that, you know, that is, you know, a huge part of the kind of easy button within health systems to be able to have, you know, the Galleri test within their normal workflow, both from the ordering side as well as the test results coming in. It really just fits into the entire workflow of a physician, so it makes it much more likely to be able to be integrated into a health system. You know, that implementation is starting now, and really in the second half of the year we'll start to see some integrations into actual health systems there.

You know, look for that to build over the, over the second half of the year. You know, Andy, maybe some discussion on the, you know, Quest side, what we're seeing there, as well as the Salesforce expansion.

Sure. With both Quest and Athena, we're seeing continued adoption of electronic ordering with Athena and Quest. Indeed, we've got about 2,000 healthcare providers now who have ordered through either the Quest or Athena integration, which has led to over 30,000 tests being deployed through either the Quest or Athena integration since we launched both of those integrations. We're very excited about the continued use of Quest and Athena by our customers. As Bob said, it really does provide that easy button for them. With Epic now launching on top of that, it provides another kinda easy button for, as we announced in our press release, 450 health systems, and those are the big health systems across the U.S.

Essentially any health system that was on the Epic system in November 2020 or later is gonna be eligible for our Epic or integration. In terms of the Salesforce, you know, we're gonna have completed that expansion by the middle of the year. With the ASCO and data coming out for both NHS-Galleri and PATHFINDER 2, and potentially an FDA approval at some point, you know, later this year or early next year, that's gonna give the sales force a lot of wind at their back to continue the momentum that we've seen with Galleri that we're reporting today.

Okay. Yeah. Very helpful, guys. Appreciate it.

Your next question will come from Daniel Brennan with TD Cowen. Your line is open. Please ask your question.

Great. Thank you. Thanks for the question. Maybe just starting off, I know there's a question already about the feedback so far since the NHS Galleri data are out, but maybe can you just share a little bit more on that? We'll, we'll learn obviously a lot more at ASCO, but I'm just wondering with that 20% plus stage 4 shift, kind of what the feedback's been from oncologists and any particular cancers where oncologists or experts are feeling most optimistic about that shift?

You know, with this respect to the, you know, reduction in stage 4, the 20%+ reduction in stage 4 in particular, you know, that is one of the things that's really resonating with both primary care physicians as well as with oncologists. I would say over the last, you know, since that data has been released, we've seen more favorable things from oncologists who truly understand just how important, you know, that reduction is. You know, I think over the last 5 years with Galleri being out in the market, we've seen good understanding from primary care physicians and, you know, but the oncologist community has probably lagged behind in their understanding 'cause they're not frontline users of it. I think that particular piece really caught their attention quite well.

I think that piece in particular is resonating really nicely. Josh.

Oh.

No, go ahead.

Okay, great. Then maybe just in terms of, you know, the guidance range for the year, I know there's a couple questions asked about like the buckets and the drivers there, but, you know, could you help like zoom out a little bit and just give a little bit more color about, you know, between, you know, health systems, concierge medicine, direct-to-PCP? Kinda where are you guys seeing like the most traction right now? You know, how do you think about, you know, the rest of the year in terms of the guide? Does it remain in those buckets, or does anything change on that front? Thank you.

Yeah, maybe I can give a little bit, and then I'll pass it over to Aaron and Andy. They give some more color. You know, the self-pay piece remains the majority of Galleri's volume, you know, accounting for kind of 2/3 plus of the volume. You know, in terms of volume growth, you know, the brick-and-mortar physicians continue to be grow strong. You know, clearly, as we talked about our integrations with Quest and athenahealth, that, you know, helped add new providers and reduce order friction. You know, going forward, we do see the Salesforce expansion continuing to drive extra volume. You know, digital health continues to provide a great opportunity in the self-pay market.

You know, here we have access to people who are used to being in the self-pay market. That's continued to, you know, do quite well with, you know, partners like Function Health and Everlywell. Then we have, you know, the new partnership coming on with Hims and then WHOOP that we just announced. As Aaron mentioned, we'll have to see, you know, just how fast the uptake of those goes. But I think that gives you some sense. Aaron, anything to add on the color on the guide?

No. I mean, I think it's Bob's covered it. You know, we'll track to see how the quarters go and look at it again next quarter.

Okay, great. Thank you.

Your next question will come from Catherine Schulte with Baird. Your line is open. Please ask your question.

Hi, thanks for the questions. maybe first on guidance. You know, I think ASPs stepped down sequentially. How should we expect those to trend for the rest of the year? Just curious on kind of volume versus ASP assumptions in your reiterated guide. Any color on how we should be thinking about second quarter revenue?

Yeah. Maybe I'll hit the ASP piece. You know, if you recall, you know, our vision all along has been, you know, to operate Galleri at population scale. You know, we have planned for price reductions over time. As we talked about, we made significant investments in our new scalable platform and, you know, have rolled that out, you know, throughout from late 2024, you know, all the way through 2025 into this year. With that gives us the ability to bring pricing down while maintaining, you know, strong margins. In 2025, we really began to lean into the price elasticity that we see in the market. We're finding success by expanding some of our discounting programs.

Much of that happened already in 2025, and so you're seeing kind of the kinda decline as we set up new pricing structures within each of the channels. You know, within 2026, we would only expect, you know, relatively modest declines to continue other than things driven purely by mix. As the mix of the various channels, you know, changes throughout the quarters, you know, you might see price increase or decrease or on ASP based on that, but that's really gonna be a mix issue, you know, with an overlay of maybe a slight, you know, slight decline in ASP per channel.

Okay. Anything on 2Q?

No. I mean, again, we expect our growth for the year to be between 22% and 32% on the revenue side.

Okay. The last question for me. We've seen some competitors increasing their DTC advertising. We had one announce a celebrity spokesperson a couple weeks ago. I know you've talked about, you know, the Salesforce expansion, but any plans you have on the advertising side to make sure you're getting brand recognition with consumers?

You know, we have been doing a little bit more certainly in the social media channels and things to, you know, get the message out. You know, one of the things we've actually found is, you know, the competitors by competitors, you know, advertising the MCED space, that's actually brought a lot more awareness for MCED. You know, we're actually seeing, you know, while it's obviously a competitive, you know, potential competitive threat, we're actually seeing a fair amount of tailwinds from that as people would get, you know, more and more acclimated to, you know, the whole MCED space. They get more knowledge about the MCED space. When, you know, our sales team can go in and describe our product to someone who's now aware and interested, we usually end up doing very well there.

You know, so far, you know, largely a headwind. Those will continue to and probably increase our marketing spend a little bit to be able to get more message out there through social media and things. You know, probably not to the level that some of the other competitors are putting out there.

Thank you.

Your next question will come from Doug Schenkel with Wolfe Research.

Hi, this is Colleen on for Doug. Thanks for the question. A bit of a follow-up from Kyle's question on sales force expansion. Can you provide any color on how many reps are currently in the field? Is it fair to assume you're back up to levels prior to the Illumina spin? Then finally on this one, how long do you expect it to take the newly hired reps to get to full productivity?

Andy, you wanna take that one?

Yeah. We're not gonna get back to Illumina levels in terms of sales team in the field. The expansion of the sales force is in the provider channel, we're expanding territories from about 90 territories up to 120 territories. In terms of, you know, productivity of that team, we're gonna have the majority of that team onboarded and then trained around the middle of the year.

All right, thank you so much. Then just 1 on the FDA approval process for Galleri. Based on your conversations with the FDA post final PMA module submission, what's your read on whether the FDA will convene an AdCom? Our sense is that based on the timing, we should be hearing about that soon. If an AdCom is called, what do you think the key areas of focus will be, given the FDA already met at the end of 2023 to discuss MCED?

Yeah, Josh, you wanna weigh in on that?

Sure. You know, as you mentioned, good question. As you mentioned, you know, we did submit the final module of our PMA earlier this year. The FDA had accepted that file. We are in an ongoing iterative review process right now. You know, the FDA guidance on timing is typically 180 days from submission without an advisory committee, and about 320 days with an advisory committee. We'd be speculating right now about whether there will or won't be an advisory committee. We can't really comment on that right now. We've been very active in supporting the FDA's review, discussions have been very constructive, but it's unknown right now whether the FDA will hold an advisory board, and if they do, what the focus of that advisory board will be.

As soon as we learn more, if we can share that, we will. That's kind of where we are right now. We're in the middle of a very iterative review process.

Your next question will come from David Westenberg with Piper Sandler. Your line is open, please ask your question.

Thank you very much. I just wanna hit on the topic of the 22%-32% guidance. You know, you obviously came in at 37%. Can you talk about I know you didn't want to answer the seasonality question, but can you give any additional color to why there might be some of the conservatism? Whether it be, like, maybe you saw really good seasonality. Is there channel mix? Is there ASPs that would make it come in below what you came in at Q1?

I'll start and then have Aaron.

Awesome. Of course.

maybe add something. I think first part is, you know, it's just early in the year. You know, obviously this is a pretty important year for us with our FDA filing. You know, we have a number of factors out there. We have the sales force expansion. We have ASCO coming up at the end of this month. There's, you know, a number of catalysts out there that we're looking to see how they go. You know, as we mentioned earlier, we have the, you know, number of digital health partners that, you know, we've signed, but now it's a matter of seeing how fast the, you know, the uptake can go with them, how aggressive they, you know, they are in the market.

As well as, you know, it was also mentioned, you know, just, you know, some of the competitive pressures out there. In that whole mix, we kept guidance the same. As Aaron mentioned, you know, we would update again, you know, look to see if there's anything new to report out at the end of, you know, after Q2. Go, Aaron.

Got it. Bob nailed it again.

All right. Maybe I'm just gonna move on to the Epic integration. You announced that the integration is gonna be expected by the end of the year. How many health systems are you currently in active discussion with, and what's your expectation for winning testing in that other, you know, not DTC channel in the back half of the year? Can that, you know, flow through for 2027? Can that start to be the bigger channel, or am I too early on that?

Andy, you wanna give some color on that one?

Yeah. In terms of Epic, there's about 450 health systems that we're targeting for the Epic integration. As I said earlier, it's essentially any health system that is on the November 2020 or later version of Epic that's gonna be eligible for this integration. When I say 450 health systems, one health system would be HCA, one health system would be Mayo. These are big, big health systems. We're currently in the process of the technical build and go to market readiness. You know, building the tests and production environments in AWS. All that kind of technical work's being done right now. As Bob said earlier, we would actually get customers live on Epic in Q3.

The sales team currently are profiling customers to assess their, yeah, excitement and conviction around when they wanna go live on the Epic platform. We're currently assessing exactly what that list is going to look like. I don't have a specific answer for you right now. I can tell you there is a lot of excitement with our current, you know, health system adopters in terms of the Epic order integration. Could you repeat the last part of your question 'cause I didn't quite catch it?

Oh, I was just thinking about how we should think about mix between hospital and DTC channels in 2027 and beyond.

I think that's too early for us to give any guidance. A lot of that's going to be driven by when we get the FDA approval. I think it's a little early to comment on that. You know, I think Epic itself is going to, you know, give us a tailwind in terms of health system integrations. The demand itself we have to create. A health system needs to want to adopt Galleri. Epic is the easy button for them that improves the provider experience by streamlining Galleri ordering, resulting, and follow-up. Yeah, as I said, health systems are very excited about Epic order integration with Galleri. That's going to sit alongside our athena and Quest electronic order integrations as well.

Thank you for taking my questions.

The last question will come from Bradley Bowers with Mizuho.

Sorry about that, I was muted. Thanks. Just want to maybe get into something we've talked about a little differently. You know, just wanted to hear about, you know, I assume it's kind of a pre-ASCO preview, but, you know, we're gonna get NHS-Galleri and PATHFINDER full data. You know, it might require, you know, some of the slices, you know, that we've seen before, performance in deadly cancers or, you know, hard to detect or those without a paradigm. You know, is this group, you know, of the eventual customers, are they kind of conducive to these slices? You know, do they understand, you know, the superior sensitivity of Galleri or specificity? You know, also that kind of leads into how competitor dynamics have been. You know, we're about 6 months with other tests on the market.

Joshua?

Yeah, no, it's a great question. I think that it's fair to say that our customers, you know, are fairly well-versed in the performance of Galleri. You know, Galleri performance has been demonstrated in multiple large studies now. Okay, from case control studies to interventional studies and intended use PATHFINDER, you know, the PATHFINDER study, PATHFINDER 2. Now they're gonna see the full data set from NHS-Galleri. As it relates to performance, you know, we think the customers absolutely understand, you know, the very high specificity, the safety profile of Galleri, its ability to detect where in the body a cancer signal comes from with very high accuracy.

It's very strong episode sensitivity in the deadly cancers, and the dramatically improved cancer detection rate that we saw in PATHFINDER 2 relative to when added to standard of care screening and what we reported out in our press release around NHS-Galleri. We think that is very well understood by many customers, but there's still a lot of education yet to be done. Obviously, the primary care community is enormous in the U.S., and ASCO will be a big opportunity for us to share a more, a deeper look at the NHS-Galleri trial in all of its glory. We're very much looking forward to that.

That's great. You know, very excited for that. Just maybe to touch on that, you know, what does the business kinda look like post ASCO, pre-FDA approval? You know, we'll pretty much have the totality of the big data sets, but that kinda gets into, you know, uses of cash, you know, and timing of the sales force ramp, you know. How do you think about maybe managing the pedal, and maybe how does FDA approval, you know, impact the business? Is it like turning on a faucet, or is it kind of a slower build? Thank you.

No, that's one of the things we're gonna have to see is the, you know, impact of FDA approval. You know, certainly our early, you know, early research would suggest it's gonna providers and patients are both gonna view that very favorably. It's early days to exactly predict, you know, what the impact of that is gonna be.

Yeah, I mean, I'd just add, I mean, fortunately with the fundraising we did last year, you know, we've got the opportunity to, you know, intercept that inflection point if and when it shows up. I think we're well-situated.

Understood. Thank you.

Thank you. There are no further questions at this time. I will now turn the call back to GRAIL for closing remarks.

Well, thank you everyone for joining today's call. We appreciate the time and your questions, and we look forward to seeing many of you at the upcoming ASCO show.

Good day, ladies and gentlemen, and welcome to the GRAIL Fourth Quarter 2025 Earnings Call. [Operator Instructions] Please be advised that this conference call is being recorded. GRAIL Investor Relations, please begin.

Thank you, operator, and thank you all for joining us today. On the call are Bob Ragusa, our Chief Executive Officer; Aaron Freidin, our Chief Financial Officer; Josh Ofman, President; Sir Harpal Kumar, Chief Scientific Officer and President, International; and Andy Partridge, Chief Commercial Officer. Before we get underway, I'll remind you that we'll be making forward-looking statements based on current expectations. It's our intent that all statements other than statements of historical fact, including statements regarding our anticipated financial results and commercial activity will be covered by the safe harbor provisions for forward-looking statements under federal securities laws. Forward-looking statements are subject to risks and uncertainties. Actual events or results may differ materially from those projected or discussed. All forward-looking statements are based upon currently available information, and GRAIL assumes no obligation to update these statements. To better understand the risks and uncertainties that could cause actual results to differ, we refer you to the documents that GRAIL files with the SEC, including GRAIL's most recent quarterly report and upcoming annual report. This call will also include a discussion of GAAP results and certain non-GAAP financial measures, including adjusted gross profit and adjusted EBITDA, which exclude certain specified items. Our non-GAAP financial measures are intended to supplement your understanding of GRAIL's financials. Reconciliations of the non-GAAP measures to most directly comparable GAAP financial measures are available in the press release issued today, which is posted to our website. And with that, we turn to Bob.

Good afternoon, everyone, and thank you for joining us to review results for the fourth quarter and full year 2025 and discuss recent business updates. 2025 was a year of significant commercial growth for GRAIL, and we have shared a number of exciting developments so far in 2026. We issued a press release this afternoon with top line results from our NHS-Galleri trial. We observed a substantial reduction in Stage IV cancer diagnosis, increased Stage I and II detection of deadly cancers and a fourfold higher cancer detection rate, outcomes that matter for patient care. While there was a trend towards reduction in combined Stage III and IV, the trial did not meet the primary endpoint of statistically significant reduction. These data show the benefit of multi-cancer screening with Galleri and provide the strongest evidence for the recommended annual screening interval. Harpal will talk through the top line NHS-Galleri trial results shortly. In our earnings press release, we also noted full results from all 35,000 participants in PATHFINDER 2 and were consistent with data presented from the first 25,000 participants presented at ESMO last year. We anticipate presenting full data from both NHS-Galleri and PATHFINDER 2 in mid-2026. Based on strong results from the NHS-Galleri and the PATHFINDER 2 study, we also announced today that we are moving forward with a planned expansion of our field sales and medical team. We believe this expanded engagement will enable us to continue to drive commercial momentum. To recap quickly on the strong commercial performance for Galleri in 2025, which we shared in January, the U.S. Galleri test volume grew 36% to more than 185,000 Galleri tests and U.S. Galleri revenue grew by 26%. Our prescriber base is now approximately 17,000 providers, up 30% from prior year. Galleri's growth in 2025 was driven by both breadth and depth of prescribing. We have been in the market with the Galleri test now for more than 4 years. And from the launch of Galleri through December 31, we have sold almost 0.5 million Galleri tests. We remain on track for continued commercial growth in 2026 with new and expanding partnerships, including digital health opportunities and further integration into health systems. We are focused on expanding awareness of multi-cancer early detection and Galleri's important performance and capability differentiation. We anticipate growing patient, provider and employer conviction in Galleri as other performance, safety and clinical utility data sets are read out. A few weeks ago, we announced that we completed our PMA submission with the FDA. The PMA marks a critical step forward, making Galleri available to more people and advancing early detection to provide a significant public health benefit. The submission represents years of focus, disciplined work to achieve design, development and validation of Galleri in large, diverse screening populations. Josh will share more about our PMA later in this call. Additionally, earlier this month, the Nancy Gardner Sewell Medicare Multi-Cancer Early Detection Screening Coverage Act became federal law. This establishes a Medicare coverage pathway for FDA-approved multi-cancer early detection tests. As a leading MCED developer, it is our privilege to stand with legislators, patient advocates, clinicians and researchers who have championed the cause. I'll now hand it over to Harpal to discuss top line results from the NHS-Galleri study.

Thank you, Bob. We're very pleased to share top line results from the NHS-Galleri trial. I want to begin with a huge thank you to the more than 142,000 participants who took part in this study as well as to NHS England, the cancer prevention trials unit at Queen Mary University of London, cancer alliances, investigators and the clinical teams whose dedication made this landmark trial possible. Detailed results from the NHS-Galleri trial will be submitted for presentation at the upcoming ASCO meeting in Chicago in late May. The design of the NHS-Galleri trial was informed by a large body of evidence showing that across multiple cancer types, reductions in late-stage disease are strongly associated with reductions in cancer mortality. While we did not observe a statistically significant reduction in combined Stage III and IV cancers through the trial, which was the primary endpoint of the study, there was a favorable trend after the prevalent screening round, and we saw compelling evidence of Galleri's benefit. Comparing the two arms of the study, Stage IV diagnoses in the prespecified group of 12 deadly cancers decreased with each year of sequential Galleri screening, with a greater than 20% reduction in the second and third rounds. Similar reductions were observed across all cancers. The reduction in Stage IV cancer diagnoses is a critically important outcome, which we believe can lead to more effective intervention for patients, particularly given the substantial and growing arsenal of effective treatments for many Stage III cancers. In fact, there is a dramatic improvement in survival for many types of cancer at Stage III as compared with Stage IV. These results are the first time a multi-cancer early detection test has demonstrated population scale stage shift and reduction in metastatic disease in a randomized trial. Screening with Galleri increased the overall cancer detection rate fourfold compared to standard of care and identified substantially more Stage I and II cancers in types that are typically detected at late stage. Screening with the Galleri test also resulted in a substantial reduction in the number of cancers detected clinically through emergency presentation, which are associated with significantly higher mortality and health care costs. And these benefits came with a strong safety profile. No serious safety concerns were reported in any of the approximately 70,000 participants who received the Galleri test across 3 rounds of testing. This is the first randomized multi-cancer early detection data set and is unprecedented in scale. Additional analyses are underway to better understand these rich data. As with any study, it's important to evaluate the results in the context of the design and execution. One observation is that we saw higher-than-anticipated incidence of Stage II cancers in this trial as compared with prior study experience. The number and distribution of cancer stages across screening rounds suggests the potential for a stronger effect with longer follow-up as data matures. And so we're planning to extend data collection by 6 to 12 months, and we'll reevaluate the impact with more mature data. In both the U.S. and the NHS data, the time to diagnostic resolution appears to improve over time as physicians gain experience with the Galleri test and diagnostic workup. Our learnings from this trial enrich our understanding of cancer biology, multi-cancer screening and the importance of implementation, particularly in ensuring rapid and thorough diagnostic investigation after a positive test result. Our mission is to detect cancer early when it can be cured. And we're delighted that these results show the potential for more patients to receive treatment with curative intent and have more time with their family and friends. We believe this is the best chance to bend the cancer mortality curve at population scale. As a reminder, the data we're sharing today is limited to our top line analysis. We plan to submit the detailed results for presentation at ASCO later in the year. I'll now pass it to Josh Ofman to review more about our recently completed PMA application.

Thank you, Harpal. At the end of January, we completed the submission of the final module of our PMA application to the FDA for Galleri. We're extremely proud of this pivotal milestone in advancing early cancer detection and addressing unmet needs in cancer screening. From the beginning, GRAIL has been completely committed to rigorous scientific and clinical evaluation to ensure that multi-cancer early detection testing is supported by strong data. The PMA submission is focused on test performance and safety results from 2 large registrational studies, including the first 25,000 participants in the U.S.-based PATHFINDER 2 study with 1-year follow-up and data from the prevalence screening round or the first year of the NHS-Galleri trial, the largest and only randomized controlled intended use trial of any MCED test. The PMA submission is also supported by a bridging analysis to compare performance of the version of Galleri used in our registrational trials to the updated version that has been submitted to the FDA for premarket approval. The results from the first 25,000 participants enrolled in PATHFINDER 2 were presented in October at the ESMO Congress. And we've now completed the analysis of the full 35,000 participants and the results are consistent. The performance data from the prevalent screening round of the NHS-Galleri study, including metrics focused on test performance, clinical validation and the clinical benefit of detection at Stages I through III, including a reduction in Stage IV were also included to further enhance the data set and provide additional data on more cancers to the FDA. As a reminder, the FDA designated the test as a breakthrough device in 2018. The PMA was submitted at the end of January, and we are anticipating about a 12-month review period. To discuss our fourth quarter financial results, I'll pass it off to Aaron.

Thanks, Josh, and good afternoon, everyone. I'm pleased to present our results for the fourth quarter and the full year of 2025. Fourth quarter results were strong with revenue of $43.6 million, up $5.3 million or 14% as compared to Q4 2024. Total revenue for the quarter is comprised of $42.3 million of screening revenue and $1.3 million of development services revenue. Development services revenue includes services we provide to biopharmaceutical and clinical customers, including support of clinical studies, pilot testing, research and therapy development. Full year total revenue was $147.2 million, up 17% from full year revenue in 2024. Full year 2025 revenue was comprised of $138.6 million of screening revenue, up 28% over full year 2024. U.S. Galleri revenue in 2025 was $136.8 million, up 26% over 2024 and in line with our guidance of 20% to 30% growth. Revenue also included $8.6 million of development services revenue, a decrease of 49% from 2024. We are seeing continued demand for the Galleri test, and we sold more than 57,000 tests in the fourth quarter and more than 185,000 tests for the year. Screening revenue of $42.3 million in the fourth quarter was up 34% as compared with the fourth quarter of 2024, primarily based on an increase in sales volume. In 2025, we began leaning into the price elasticity we see in the market and are finding success in expanding access with our discounting programs. Development service revenue in the fourth quarter of 2025 was $1.3 million. Net loss for the fourth quarter of 2025 was $99.2 million, an increase of 2% as compared to Q4 2024. Net loss for the full year was $408.4 million, an improvement of 80% as compared to the full year 2024. Net loss in 2024 included goodwill and intangible asset impairment of $1.4 billion. In addition, net loss for 2025 and 2024 included amortization of Illumina acquisition-related intangible assets of $138.3 million. Non-GAAP adjusted gross profit for the fourth quarter of 2025 was $23.1 million, an increase of $5.2 million or 29% as compared with Q4 2024. Full year non-GAAP adjusted gross profit was $73.6 million, an increase of $15.8 million or 27% as compared with the full year of 2024. Primary drivers of the increased margin were revenue mix and efficiencies of scale related to increased Galleri volume. Adjusted EBITDA for the fourth quarter of 2025 was a negative $71.8 million, representing an improvement of $12.2 million or 15% as compared to Q4 2024. Adjusted EBITDA for the full year 2025 was a negative $320.6 million, an improvement of $163 million or 34% as compared to the full year 2024. We ended the quarter with a cash position of $904.4 million. This balance included $436 million in proceeds from both our private placement of equity in October as well as our ATM equity issuance program in November and December. As a reminder, we have shared in the past our long-term gross margin target of 50% to 60% at scale. We are making good progress on attaining these margin targets. And as we saw in the third quarter, volume efficiencies make a big difference. In connection with our supply agreement with Illumina, we are obligated to pay them a royalty on revenues. Those royalty payments are suspended until December of 2026. When resumed, we expect to pay Illumina a royalty in the high single digits, subject to certain terms and perpetuity on net sales generated by our products on revenues in oncology. We expect that these payments will make an impact on our gross margins beginning in 2027. Given strong performance in the self-pay market and the momentum we are seeing with positive data readouts, we are reiterating the guidance we shared in January today of Galleri sales growth of 22% to 32% and cash burn for the full year of 2026 to be no more than $300 million. Our cash runway extends into 2030, and we are well positioned to navigate growth over the next several years as we pursue critical milestones toward broad access. Bob, back to you for concluding remarks.

Thanks, Aaron. To close, our teams at GRAIL continue to do great work advancing towards our vision of population scale multi-cancer early detection. We are approaching our 10th anniversary as a company this March, and we are energized by recent milestones and achievements, including the consistently strong performance we are seeing for Galleri across our studies. We presented positive registrational clinical study results for the first 25,000 participants in the PATHFINDER 2 study in October and today shared top line results for the NHS-Galleri trial and the full 35,000 participant PATHFINDER 2 study. We're looking forward to data presentations for both studies later in the year. The business continues to grow, and we are excited about expanding our partnerships with digital health companies and health systems to continue to expand access to Galleri. We have now completed our PMA submission with the FDA and new federal law provides the pathway for Medicare to cover FDA-approved multi-cancer early detection tests. We're in a strong financial position with more than $900 million in cash as of December 31st. I'd like to thank each of our employees for their incredible commitment and dedication to our mission to detect cancer early when it can be cured. We'll now turn the call over to question and answer. Operator, please go ahead.

[Operator Instructions] Our first question will come from Subbu Nambi with Guggenheim.

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?

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.

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?

Yes. Thanks again. Josh, do you want to take that?

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 that 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.

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?

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.

Your next question will come from Kyle Mikson with Canaccord Genuity.

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?

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.

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. 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.

And then I hate to nitpick, 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.

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.

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.

Your next question will come from Doug Schenkel with Wolfe Research.

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? 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 SKUs, anything like that?

Yes. Thanks, Doug. Maybe, Josh, I'll hand over to the FDA questions to you.

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. 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.

And maybe Harpal, you want to maybe just comment...

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. 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. 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. 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. 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.

[Operator Instructions] your next question will come from Catherine Schulte with Baird.

I guess, first, just on that last point of extending the trial follow-up by 6 to 12 months. Is that something that you and NHS have already agreed on? And I guess, what is the goal of what you will see in that 6 to 12 months? Is it to push more on the Stage III reduction? Or is there something else that NHS is hoping to see?

Yes...

Yes. Thanks, Catherine. We haven't discussed it in any detail with the NHS yet, but I think it's -- I really can't see any obstacles in being able to do that. What it requires is not going back to participants or clinicians. It would be a continuation of passive data collection, which is already being recorded. And so it's just about the passage of time and agreeing with the NHS team that we can get access to that data. I think that will -- I don't foresee any significant obstacles in that regard. And in answer to your second question, yes, what we want to see is particularly the control arm data maturing more than we've been able to see. And perhaps if I just elaborate a little bit on that, what you tend to see in a screening trial -- in any screening trial is that you're finding cancers that would have been detected later. And so if you think about what that means in practice, you're pulling forward into your intervention arm cancers from the future. For a control arm of the study, those cancers may not yet have manifested. So when you're comparing 2 arms of the study, what you'd like to have is long enough follow-up that you can compare the 2 arms really, really well together. And what we've concluded looking at the data is we probably need a longer follow-up time to be able to do that adequately.

And then for the NHS, I know they put out their National Cancer Plan earlier this month and still reiterated their commitment to and interest in multi-cancer early detection. We've got OLS closed an application process for what sounds kind of like a AdAC-related study using multi-cancer tests in primary care to triage patients with nonspecific abdominal symptoms. Is that something that you guys are involved in? And maybe just talk to the broader relationship with NHS.

Yes, happy to do so. So we've been having ongoing conversations with the NHS really over the last 5 or 6 years. Those conversations continue very actively and certainly will continue here on in. Of course, we were very pleased to see in the NHS Cancer Plan a couple of weeks ago, a number of references to multi-cancer early detection and indeed, the excitement within the NHS and the Department of Health in England for the possibilities that this new technology offers for really transforming the landscape for cancer patients. So the multiple references in the Cancer Plan, I don't think it's an exaggeration to say, comes from the conversations and relationships we've been having with the NHS over the last 5 or 6 years. With respect to the second part of your question, yes, there is a process underway to further evaluate the role of multi-cancer detection in a symptomatic context. And this is a follow-up from our SYMPLIFY study that we reported a couple of years ago. Necessarily, the Department of Health has to go through a competitive application process. It doesn't -- it can't just offer that opportunity to GRAIL. So that application process is underway. And as you might expect, we are applying to be part of that process and are hopeful that, that will move forward. Certainly, we believe our data from the SYMPLIFY study is very strong and very encouraging in that context.

Our next question will come from Dan Brennan with TD Cowen. [Operator Instructions]

Maybe just one on Medicare. So assuming you're successful with FDA, I'm just wondering, I know Medicare, you have the favorable pathway, obviously, and FDA approval, assuming you get that, that would be terrific. But we're under the impression that Medicare does consider clinical utility. So how do you think they would look at the NHS trial? And how would that potentially impact the Medicare decision?

Josh, do you want to take that?

Great. Yes. Obviously, Medicare is going to -- upon FDA approval now has the statutory authority to provide coverage for multi-cancer early detection tests and we'll initiate a national coverage analysis and really look very carefully at the data. And we believe we're going to have a very robust package of data to submit to CMS, including all of our registrational trials, everything about NHS-Galleri, including the substantial Stage IV reduction, the fourfold increase in the population cancer detection rate, the increase in detection of Stage I and II cancers and also very strong clinical performance overall. And so we think that, that combined with our real-world evidence, our clinical surveillance program and the REACH study in Medicare patients at the time of the NCD will be a very robust package for them to evaluate. Again, Medicare has never evaluated a multi-cancer early detection test before. There is no known bar that has been set. And so we feel like we're going to be able to provide them an incredibly robust package of evidence to consider coverage for Galleri.

Okay. And then maybe just on -- I appreciate the Stage IV is down, which is terrific, but the III, given some of the anomalies you discussed was up. Like collectively across Stage III and Stage IV, can you say if there was a decrease and kind of what the level of that decrease was?

Yes. I can't really comment any further at the moment. There was not a statistically significant reduction. But what we did see was a trend towards a reduction over time, and that was a favorable trend. I think that's as much as I can say at the moment, but we are planning to present the full results at ASCO later in the year.

And I mean if I can sneak in one final one. So the trial was set up for 3 years. Obviously, it was going to be a surrogate for mortality because mortality would just take too long. So I think that was pretty well established. Was there a decision when you set it up for 3 years as opposed to maybe setting it up with a longer follow-up period, kind of how that decision was made? Obviously, it sounds like now you're hoping, obviously, the longer follow-up will still prove out the study. But I'm just wondering when you went into it, how was that decision made?

Yes. I mean, look, as with any study, it's designed and sized and powered with the best information you have at the time. And at the time, we felt that 3 rounds of screening followed by a year of follow-up would be sufficient. I think with the benefit of hindsight, we probably should have allowed for a longer follow-up period. There have interestingly been a number of publications over the last couple of years about screening studies in general, not just about NHS-Galleri, which make this exact point that the trial should be followed up for longer than 12 months post the last appointment. As I say, this trial was designed 6 years ago, and that was the best information we had at the time. But as I've already touched on, on this call, we have the ability to continue follow-up. So that's what we're going to be doing.

And it's probably just worth noting that most screening trials have gone on for decades, at least 1 decade, if not 2. And so this was a very -- in the context of screening trials, this was actually a very short trial with a very ambitious endpoint. And that's part of the story here. But it is the first time that an MCED test has shown the ability to shift the stage diagnosis for the population in a randomized clinical trial. And I don't think we should let that kind of go by.

For our next question, we'll return to Kyle Mikson with Canaccord Genuity.

So just given you see these results now, at this point, can you go to the FDA kind of narrow or adjust, let's say, your label maybe to the 12 cancers that you performed the best in or maybe like an older patients, like an older subset perhaps? And just generally, like how does this impact your thoughts on the -- like a potential advisory committee meeting based on there was an -- there was an AdCom back in '23 already?

Yes, sure. Again, we don't think that this finding is going to impact the approvability of Galleri with the FDA. The FDA is clearly going to be focused on clinical performance and safety and the profile of data that was delivered to them. And in that context, we will work through labeling with the agency. Should they seek clarification on the intended use, and narrowing of the indication to the things that you suggest, we'll be negotiating that with them in due time. But we feel like we have a very strong and compelling evidence package for our current intended use, which is adults at elevated risk for cancer such as adults over the age of 50 and with additional risk factors if they are younger than the age of 50. So we feel like we have a robust package, and we'll see where the labeling ends up.

Yes. And maybe just to add to that, the -- it's also we haven't really brought up this across the 3 rounds of the large participants in NHS-Galleri as well as the 35,000 in PATHFINDER 2, there was no serious adverse events across the entire trials. So those are really large numbers. So from a safety perspective, it was really good showing up.

And we think the benefit risk profile is quite compelling as a result of that.

And just to add something that Josh said, in relation to your point about the 12 cancers, the reason we specify this group of 12 cancers is because it represents 2/3 of all cancer mortality. So if you can make a difference in that group, you really are making a dramatic impact at population scale. But I would draw your attention to something that's in our press release, which is when we talk about the Stage IV reduction and the fact that it's more than 20% in the second and third rounds of screening, yes, it's true for the 12 cancers, but it's also true for all cancers. And so I don't think there's any reason at this stage to think that we should be narrowing our claims only to the 12 cancer types.

That's a great point, Harpal. Thank you for making that. And just to your last question about the AdCom. It's certainly possible that there can be an AdCom. The FDA has already held an AdCom. And so we are not sure whether that's going to happen. We will wait and see. But we've made the case to the FDA that based on their prior AdCom that they've already held and the fact that we've addressed all of those issues in our submission, which was just completed recently, that there's likely no need for one. But we'll see what the FDA decides.

All right. Super helpful. Just a quick follow-up. Obviously, the NHS-Galleri results are pretty relevant to the FDA submission, but I don't believe there's much read-through to USPSTF inclusion. So in a worst-case scenario, you don't get FDA approval, which again is not the -- you guys expect that. You could get a USPSTF inclusion, get into -- or get Medicare coverage according to the legislation and so forth. Are your thoughts on guideline inclusion unchanged? Or is that -- you still don't think that's the necessary milestone for you guys that FDA is most likely going to happen?

Well, I'm not sure I'm fully following your question, but let me try to take a stab at it. We think the first most important milestone is to get an FDA approval. And we think that, that is going to be an incredible moment for patients and provide amazing amounts of conviction in the clinical community and the payer community. Many of the payers have told us that, that would be the gating step for them. They would like to see an FDA approval before they would provide coverage or consider Galleri for coverage. And then obviously, there will be a CMS, NCA, National Coverage Analysis decision as we've discussed already. So we think those are the most critical things. And USPSTF evaluation would then come after that. And obviously, that was -- that is important if you don't have a coverage pathway within CMS. And that's why the USPSTF pathway was put into place because the CMS had no statutory authority to provide coverage for preventive services. But the CMS does have statutory authority now. So we see the USPSTF as being supplemental to that. But in terms of guidelines, we think the FDA approval is going to be one of the most critical parts and then the very strong and robust evidence base we have about all the clinical benefits that Harpal has described.

Yes. Just to clarify, I was just saying like if the USPSTF committee if they're going to take this data into account, but it's -- we're talking [indiscernible] in the future probably. So maybe it's not relevant. But anyway, thanks for the time.

There are no further questions at this time. I will now turn the call back to GRAIL for closing remarks.

We look forward to presenting full data from our 2 registrational studies in mid-2026, a longitudinal randomized controlled NHS-Galleri trial, including clinical utility and performance and the full 35,000 participant PATHFINDER 2 study. So we look forward to providing future updates, and thanks, everyone, for joining the call.

Ladies and gentlemen, this concludes the call. You may now disconnect.