Good morning, everybody. So I'm Doug Shankle from Wolf Research. I lead our life science tools, diagnostics, and labs segment. It's my pleasure to host GRAIL, and on behalf of the company, we have a few folks here right now, but up on the stage with me, we have Josh Ofman, President of the company. So Josh, thanks for being here. Lucky me twice in, like, a week, week and a half, so it's good to see you guys. As I'm sure all of you are aware, GRAIL is a company that has developed blood-based tests to detect cancer early, primarily through its Galleri Multi Cancer Early Detection Test. I—there is a lot to talk about. You know, the stock has obviously been on a tear all year. You just hosted a really fantastic Analyst Day last week, and tour. So just to try to put some structure around the conversation and to provide everybody with a roadmap, there's really five topics I want to go through. I want to talk about the Analyst Day, recapping really some key takeaways and how we should think about that as we start to look ahead to 2026 and 2027. I then want to take a step back and talk about the use of MCED and essentially how you start to broaden use of Galleri. And interwoven in there, I want to talk a little bit about competitive dynamics. The third topic is really the regulatory and reimbursement pathway, which I think is front and center for a lot of folks in terms of how they're trying to think about how things evolve over the next several years. Then we want to close on commercial strategy and the financial outlook. That's a lot. Why don't we hop into it? Thanks again, Josh, for being here. My pleasure. Thank you for having us. All right. So Analyst Day. Yeah. You packed a lot into a short period of time down in North Carolina last week between regulatory reimbursement, focusing on clinical evidence, a really neat panel discussion. You talked a bit about your commercial strategy, and the tour was fantastic of the lab. With all that said, if there were two to three things you wanted people to take away from the Analyst Day, what are they? I think first and foremost, you know, we've been in the market now for several years, and we're seeing a lot of momentum in the market, different segments of the market, some which are, you know, like self-employed insurers to, you know, the clinic channel to this new emerging whole area of digital health. A lot of excitement. The second point is we are very excited about the Pathfinder 2 data. The performance of the assay looks pretty remarkable. We're very excited about the potential to improve public health. We now have a tool that is simple enough to be contemplated as part of an annual physical exam for every adult at elevated risk for cancer. That's a big idea. We have technology that continues to improve over time as we've versioned it, and it's showing up in our clinical trials. The other big message is the performance, you know, is very exciting. And then finally, that this is real. The lab, we've already made the big investments into a lab that can scale to over 1 million tests a year and ultimately to over 6 million tests a year. We've made those big investments. We're ready, and we're going to be submitting to the FDA in the first quarter. Actually, perfect segue. You did narrow the timing of the PMA submission to the first quarter. Before that, it was first half. Technically the same, just a little bit tighter. With that in mind, the NHS-Galleri data is set to read out middle of next year. You know, as we think about key, you know, essentially one, one of the most important milestones for the company getting through the FDA, how would you describe your confidence at this point? You know, we feel good. It's the first time an MCED has ever been reviewed at the FDA. We're excited about the opportunity. You know, we've got amazing data from, and the largest clinical genomics program, I believe, that's ever been undertaken. It'll be one of the biggest packages of data the FDA has ever seen for a diagnostic test. You know, we're going to be submitting, you know, over 90,000 patient records to the FDA. I don't think they've ever experienced anything like that. You know, we'll submit the full Pathfinder 2 data set on the first 25,000 that have one year follow-up. We'll submit the full first year prevalent round screening from NHS-Galleri from the intervention arm, which is another 70,000. We'll do the bridging study between our prior version, which was in the studies, and the commercially available version now. We feel great about our chances. I think a lot remains to be seen. You know, will there be an advisory board? What will the label end up looking like? We have been reassured that no matter what the label looks like, we are going to be able to return every result. Which is really what matters. Yeah, I was going to say, so what do you, there's a lot of debate in the investment community about what the FDA is looking for. We got a little bit of a lens into that when they did their meeting on MCED, which I think was end of last year, right? Everything's blending into each other. Do you have a— End of 2023. Was it 2023? No, I was like, was it end of 2023, end of 2024? They've done two. Yeah. And so, you know, those have been very informative. What do you think you need to do to get through the FDA at this point? They've been very clear. They're looking at clinical performance and safety. They're not looking at clinical utility. They're not looking at mortality. They've been pretty, pretty clear. The other thing that they've been clear about is that the CSO capability is a critically important part of an MCED. You know, we think they're going to be looking for a very positive benefit to risk profile. As you saw with Pathfinder 2, when this assay is added, when Galleri is added to standard of care screening, the cancer detection rate in the population improved by seven-fold compared to the A and B rated screening tests, and three-fold compared to any, all the recommended screening tests. That's just an enormous public health improvement. I think from a performance perspective, they're going to be looking to us. How do we define the benefit risk profile? The benefits that we see are the cancer detection rate, an extremely high PPV of 62%, orders of magnitude higher than anything that's ever been seen before in cancer screening, a very low false positive rate in Pathfinder 2. It was 0.4%. Again, an order of magnitude lower than anything that's ever been seen with cancer screening before. CSO accuracy, that's about 90%, which again, has never been seen before, right? It's the only time they'll ever see data like that. Sensitivity, which is very strong. Overall sensitivity of 40% for any cancer. Let's remind you that, you know, of all the colorectal cancers found in this country, only about 40-50% are found through screening. We're finding that of any cancer. In the 12 deadliest, deadly cancers that represent about two-thirds of deaths, our episode sensitivity was well over 70%. I mean, this kind of performance has a very positive benefit profile. On the risk side, we saw no serious adverse events in any of our trials related to diagnosis, and only about 0.6% of patients had an invasive procedure at all, and there were twice as many in those who had cancer versus those who did not. We had a very short time to diagnostic resolution, about 36 days for people who had cancer. That gets people into cancer treatment much faster. Enormous benefits with very few harms equates to a very positive benefit risk profile. Return of results you talked about, we'll have all of that through Pathfinder 2, to, do we get that out of NHS as well? Oh, yeah. Okay. I mean, again, I've said this, but you know, you can really only define the benefit risk profile in an interventional study. Right. Which is why I'm so surprised some companies are launching their tests just based on case control data. We've seen time and time again, those data do not replicate when they put them into patients. Unfortunately, that's true. You know, we were trying to be responsible about it. We didn't launch our assay until we saw the Pathfinder data and validated that when you put this into a screening population, the test actually works. Until you do that, you can't know anything about the benefit and risk profile of your product. That's what doctors want, and that's what consumers want. They want to know that I'm taking a test that has some established benefit risk profile. I want to respect the discussions with the FDA, which you don't want to air out publicly, every update. I imagine, you know, given you have highlighted the seven times higher detection rate, that that's something that you probably feel would resonate with the FDA. Absolutely. If you think about single cancer screening, so just look at, let's look at, Mammography or Cologuard. You know, their sensitivity is basically their colon cancer detection rate and their breast cancer detection rate. That's their sensitivity. For a multi-cancer test, there's no sensitivity, you know, measure cancer- by- cancer that really matters. It's the overall cancer detection rate that is the sensitivity measure that matters for an MCED. You know, if we're introducing Galleri and adding it to standard of care screening and increasing the screen-detected cancer detection rate by seven-fold, that is just an enormous benefit, for public health. Because we're not going to bend the cancer mortality curve finding 14% of cancers, which is what single cancer screening does. We need to dramatically increase the number of screen-detected cancers in the population. If you can do that very safely, with a very low false positive rate, high CSO accuracy, rapid diagnostic resolution, that's, I think, the secret sauce to really improving public health. CSO, cancer signal origin, that is a key differentiated attribute of the Galleri test. If the primary way on a positive that you dealt with that was then to immediately reflex to imaging if you did not have CSO performance at the level you do, do you think that would be a problem with the agency? I mean, the agency has been very clear, that they believe the CSO prediction capability is a critical component of any MCED. I don't think they believe that, sending somebody a result that says you have, you probably have cancer is a safe idea. Right. Again, to get people, every one of those people to go into whole body imaging, which is 25 millisieverts of radiation if it's a PET/ CT, and a lot of radiation if it's a three-part CT scan of the body, those levels of radiation have been shown in recent JAMA articles to cause cancer. What is the safe and appropriate and affordable and practicable workup? It needs to be directed. Our workups based on our CSO prediction are either in a, you know, you get a stomach, colon, esophagus, larynx, you're going to do an endoscopic procedure right off the bat and find that cancer. If it's liver, pancreas, gallbladder, or something in the pelvis, you're going to do a very focused, you know, scan of that organ, like a pancreas scan or a liver scan or a pelvic scan and find the cancer most often. In commercial, if you don't find the cancer with a good look, we offer a free repeat Galleri test to resolve it right then and there. We have good data to support that that's the best way to do it. I wouldn't think the FDA would chime in on testing interval. Do you agree with that? Yeah, I think it's a good assumption. They may, I, they haven't with prior tests. Typically, you don't see that. Yeah. They haven't seen it. We believe, based on all the data that we have, including a large cohort study that we did with the American Cancer Society, that the dwell time of cancers, like how long cancers stay in each stage, is somewhere between 12 and 13 months, which means if you want to find cancers in earlier stages, annual screening is the right frequency. We may learn in the future that for certain higher risk subgroups, it needs to be done more frequently than that. Remember, the problem is everything we know about the natural history of cancer is pretty much based on imaging. Now that we have this biological signal from cancers that we're following, we're learning that cancers are moving a lot faster than we thought based on imaging. That is challenging the whole system. All of that makes sense. Blood is a convenient way of doing annual testing. We, I mean, CMS at this point, as we all know, is not authorized to reimburse, which we'll talk about in a second. With that in mind, I presume there's been nothing out of CMS that would help us have a better understanding of how they would think about testing interval on an MCED, given they can't even reimburse it. I think that's a fair statement, but I will tell you that they approved the Medicare REACH study, which is annual testing. Okay. You know, they've reviewed our protocol. They reviewed our data extensively. They approved this study. They're paying for it, including the workups. It's a Medicare REACH study in 50,000 Medicare beneficiaries for three consecutive years. The biggest study they've ever approved for an unapproved test prior to this was 5,000 people. The average study that they approve in this kind of IDE setting is about 350 people. This is an unprecedented study that they approved for annual testing. Tells you something, I think. Are you taking it up a level? Anything you're hearing out of Washington, D.C. on whether or not there's some momentum picking up? I'm sure this could change, given what we've seen over the last year. Things could be changing day to day. What are you hearing in terms of momentum towards passage of MSAD? Great momentum. I mean, you know, you have a majority of both houses of Congress sponsoring the bill, the key committee chairman, you know, sponsoring it, a great markup in the Ways and Means Committee, a great hearing at Energy and Commerce. It is the most popular bill in Congress for healthcare, bipartisan and bicameral, supported by over 730 different advocacy organizations. I mean, it's one of the most supported bills in healthcare. What we need is healthcare to be in one of these vehicles. If healthcare is in a vehicle, I think we have high confidence the MSAD bill will be part of that. The question is, will there be a vehicle? As you remember last year, at the end of last year, it was in. Yeah. They, all the healthcare got stripped out. That could happen again. We do not know what the vehicle will be this year. There is usually an end-of-year must-pass legislation, but that could get kicked into January now based on the government shutdown. A lot of good momentum, but we are looking, you know, we need to figure out what Congress is going to do about a basic vehicle. If we get a bill passed, I think collectively, you and I think we've talked about the idea that, as proposed, you would probably get about $500 per test. That is correct. Okay. $508 or $509, something like that. Okay. And then from a timeline standpoint, thinking about timeline through the FDA, which is obviously a parallel process, but let's say you get through the FDA late next year or late 2026, early 2027. So about a year. And then if we get a CMS, if we get an MSAD law passed on that side, then you would need a national coverage decision policy, and then you would have to work through CMS. The bill kicks in 2028, right? 28. Okay. It would start, they'd start having coverage authority in 2028. You'd have 2027 to work with them on an FDA-approved product to get them through the national coverage policy process and hopefully begin reimbursing that first year of eligibility in 2028. Twenty-eight would be the year where if things line up. Okay. I'll actually, as we talk about it, all of a sudden, that does not feel that far away. I guess the question would be if MSAD takes longer to pass, then maybe the goalposts move out a year. Right now the— You have time because, again, the FDA approval is not going to happen until presumably the first part of 2027. You have time. You can pass the bill in 2027 as well. Okay. Super helpful. I want to go back and ask a higher level question. So keeping in mind, you know, the stock's been on a tear. I think it's up over 300% year- to- date. As we think about 2026, what are the key milestones that investors should be looking towards that could continue to drive the stock higher? Yeah, I think, you know, first is just the commercial momentum that we're seeing. You know, we're seeing great momentum. People are responding to the data really well. There are now other players in the market increasing the amount of interest in MCEDs. Obviously, we believe we've got the far superior product. That helps us, which we are going to enjoy in 2026, I believe. Our key inflection points, you know, the FDA submission, which we hope to be done in the first quarter of 2026. We'll see what happens with the FDA, whether they have an ad board or not in 2026, or whether we get the approval at the end of 2026 or not. Those are milestones. The middle of 2026, we're going to read out the full NHS-Galleri study with its clinical utility endpoint, primary endpoint of the trial. That'll be a big inflection point. There are a lot of things that I think analysts can look at about is, and to the point Aaron always makes, are we executing on our plan? You know, are we bringing our burn down? Are we getting more efficient in our spending? Are we growing in the most cost-efficient way possible, which we showed in 2025 that we can do? Are we getting that fixed cost leverage out of our lab, which we've also shown in 2025 that we have? Those are the kinds of things to look at. Can I just ask a follow-up on NHS-Galleri? Obviously, the readout in itself is super important. You're going to go into the FDA before investors and the public see the readout. Obviously, going into the FDA with that data will be seen as a positive signal. We'll get the readout over the summer. Long windup too, I still think there's some questions about what the NHS itself does with this data and what comes next there. I almost think the data readout and what it means in terms of your positioning in the United States and getting through the FDA is more important. And that's not a, you know, pro-U.S.A. thing. It's just a size of market thing. But, but how important is this readout in terms of affecting decisions within the NHS? Let me go back to one thing you said that I just want to correct. Yeah, yeah. The FDA submission will include just the prevalent round. The FDA is really not going to be interested in the stage shift, which is the primary endpoint. The primary endpoint of the trial is, is there an absolute reduction in stage three and four cancers, in the intervention arm compared to the control arm? That's really a clinical utility measure. The FDA is going to be focused on clinical performance and safety. They won't be getting all that data. They'll get the first year, the prevalent round, only from the intervention arm right now. They may ask for the control group that may have more information for them, but not a lot. You can't tell anything about stage shift in the first year. That's what the FDA is going to get. I don't think it'll be important for the FDA. I think it'll be important to know, whether that intermediate endpoint of late-stage cancer reduction absolute, which is less prone to lead time bias and other things, is occurring. Now, there are a lot of dependencies about that. What's the cancer case mix in the population? You know, and that's unknowable. Did we estimate it correctly? You know, all those things. But based on all the data we're seeing, you know, and we've seen the first year of the NHS-Galleri data, and we did a high-level press release about it, pretty consistent with Pathfinder 2, in many respects. You know, we're confident that we should be able to find, some really important results. Now, as it relates to the NHS, that's where they're going to be looking hard at that data, and that will drive their decision about whether they invest in a national screening program, or maybe they want to pilot it again, because a couple of years last year, remember, they decided it was too early to pilot it. They weren't ready to do that. They are going to look at all the data right now. They may make a decision. It may look strong enough where they say, let's roll this out as a national screening program. They may say we need to do a pilot. We don't know, but they're going to be looking hard at that data. I think then that data will also inform some of our payer discussions in the United States because that's a clinical utility estimate along with the cancer detection rate, you know, which I think will be the most important clinical utility measures. That can help you, regardless of how NHS comes out on that. Having that additional data can help you as you're talking to guideline agencies and talking to commercial payers. Is that the right way to think about it? Absolutely. That will be, you know, because payers want to look, the gold standard for single cancer screening has really been cancer-specific mortality. And, you know, again, those studies have taken 10 - 20 years to read out. They've been funded by governments with decades-old technology that's not changing. You know, here we have technology that's already changed by the, since we did the study of the NHS-Galleri, it's already different, and it's going to change more rapidly. We don't have time to do a 15-year trial. This technology would be completely obsolete. So people are going to have to get their heads around these intermediate endpoints. And we tried to pick the one that we think is the most relevant, which is an absolute reduction in late-stage cancer. Now, our primary endpoint is stage three and four cancers, but even just a stage four reduction is vitally important because remember, stage three cancers, as in the last five years, are being treated much more effectively, sometimes with curative intent now. It is really a late-stage, stage four reduction that we think will have the most important, the biggest impact, you know, on patient care and on health outcomes. Yeah. Given how long it would take to, you know, maybe do a large study that demonstrates stage shift in almost like an academically, you know, a way that would seem reasonable academically, but practically speaking, it could take a decade or two. To show a mortality benefit, for sure. Yeah. We'll be able to model some mortality, and we'll see, we'll see what that looks like. Everybody's agreed to, you know, the way you have structured the study where it really is looking at the change in two cohorts of stage three, stage four. I mean, that's almost the best way you can do it in this type of study, correct? Yeah. We got advised by, you know, the best scientists in the NHS, the best cancer researchers in the world, you know, helped advise us as we designed that study. In the last five minutes, I want to pivot to a few commercial and financial questions. When you got spun out of Illumina, you know, there is a lot of focus on how you could extend the runway, and I think you were successful in identifying a credible path to getting to 2027. Recently, you have done a, made a series of financial moves to extend the runway, I think well into 2030. Do I have that right? At least 2030. With a stronger balance sheet, I am wondering if there are opportunities to lean in, you know, keeping in mind how much focus there has been on Galleri in MCED, and making sure you extend the runway. Obviously, the focus on Galleri for MCED is not changing, but is there, are there opportunities to lean into adjacent areas? Like we talked about symptomatic cases last week at the Analyst Day. Are there opportunities to get more aggressive commercially? How are you thinking about maybe operating a little bit differently now that the balance sheet is in a much stronger position? It's a great question. I think great credit to our financial team over here for improving the strength of our balance sheet. I mean, it's really important for us. It gives us a lot of flexibility. I think the most important element is it extends our runway into 2030, and that's without the Samsung investment. That just, I think, de-risks a lot of, you know, timing of FDA, timing of CMS, some of these uncertainties that we can't know, I think is really helpful. The other important aspect is just the financial flexibility that it provides us. I think we're going to be really opportunistic. I think where we see opportunities to, you know, step on the gas commercially, if we see those chances, depending on what the NHS data look like, that could create a lot of momentum. We're still dealing with all the momentum from Pathfinder 2. and so we're going to be pretty opportunistic about that. There are digital health opportunities that are going to be international opportunities that are coming our way all the time, product improvement opportunities. You bring up an important point about the symptomatic population. We've seen incredible performance of Galleri in the symptomatic population. This is a cohort of individuals who are at elevated risk for cancer. That's our intended use. and so how we decide to go after that population, there are lots of choices that we need to make, and we're going to be looking and evaluating that right now. Because a very important finding we just released was that in that study of symptomatic people who were being worked up for cancer, our PPV was about 75%. Okay. We followed those people for two more years, and 35% of those that were thought to have a false positive converted to true positives at the signal origin that we predicted, except for one case. That is a remarkable finding. We have always known that that would likely be found because we know that you have to really look hard for these cancers because they are pretty early. Sometimes they are called false positives, and then they reveal themselves after that period of time. That is exactly what we saw in this study. The magnitude of it, the 35%, was, I think, more than any of us would have ever expected. Yeah, it's interesting. There's at least one big employer who we've heard has thought about Galleri in a way where, you know, it's almost like a self-selecting test where the folks who basically order Galleri are folks who have a family history, or maybe they smoked at some point, but didn't want to self-identify, or there's something that makes them a little bit concerned. I think the employer actually has indicated they view that as attractive because in those cases, you actually are finding a higher proportion of cancers, and ultimately, you keep them healthy, it leads to better outcomes, and you keep them in the workforce. Yeah, and the symptomatic population, that's exactly right, is an interesting one because, you know, in screening, you know, there aren't reimbursement pathways that exist, you know, but if you're symptomatic, it's no longer screening. Now you're doing surveillance or diagnostic work, and there are more reimbursement pathways for that. We're going to really evaluate this population given the data that we've seen, and, you know, figure out what the best approach is. Yeah, it seems like you're well positioned with the FDA and, you know, let's hope MCED, they'll momentum continue to see if there are alternative paths. Is it part of Galleri's intended use, or is there an alternative path? Yeah, there's some contingency plans or adjacent plans. Last thing, because I know we're over time, one of the new data points you shared last week, and I scratched this down as I was walking in, but I think you talked about a 29% repeat test rate. Over 30 now. Is it over 30%, which I think is up from 20% when you last shared data earlier this year. How important is that? We think it's really important. I think it signals too. First of all, for a screening test, to get to a 30% repeat test rate this quickly is pretty unprecedented. I mean, you know, Cologuard is a great example. It took much longer to get to these levels of repeat testing. I think what that signals to us is an affirmation in the belief of the power of the test and patients' willingness to do it. The fact that it's not reimbursed, not FDA approved yet, and we're getting that kind of response is a very important signal to us because, again, Cologuard was reimbursed, FDA approved, and took much longer to get to that repeat every three-year testing rate. We're pretty pleased with that. We know, and we know that this is the annuity feature of Galleri, and we need to drive that up. Most cancer screening tests have compliance rates, you know, sequentially in the 60-80% range. That is our goal. but I think until it is a reimbursed test, we are not going to be able to approach that. Okay. All right. We're going to have to leave it there, but that was fantastic. Really appreciate the time, Josh. Good to see you always. Thank you. Thank you.