Good morning. Thank you for joining us today. I'm Richard Meland with the banking team at JP Morgan. It's my pleasure to introduce the GRAIL team. Presenting today will be Bob Ragusa, CEO, and we're also joined by Aaron Freidin, CFO. Just a quick note, we'll have time for Q&A after the presentation, so please wait until then, and we'll get you a microphone. But with that, I'll turn it over to you, Bob.
Thank you. Appreciate it. Welcome, and thanks for attending this session. So we're pleased to be here today for the first time at this event as an independent public company. I'll direct you to quickly highlight some of the disclaimers. So if you need any more information on any of those, please see GRAIL's filings with the SEC. So GRAIL is focused on detecting cancer early when it can be cured. We know that current recommended screenings, which are limited, and most deadly cancers are found too late. We believe that multi-cancer early detection is a solution for effective population-scale screening. GRAIL is uniquely situated to address one of the most meaningful opportunities in health care. Galleri, our first of its kind multi-cancer early detection test, was designed for population-scale screening. Our expansive clinical evidence program is setting the standard in the multi-cancer early detection field.
GRAIL also has a first-mover advantage in an expansive global market. We have a breakthrough designation with the FDA. We are progressing our PMA. It's a modular PMA, and we're submitting with the FDA and expect final submission to be in the first half of 2026. We have a large global opportunity. With an eye towards the future, we've made investments in our infrastructure and operations, and I'll detail a little of that in a few minutes. Today, as we pursue FDA approval and broad reimbursement for the Galleri test, we are equipped with commercial scale and global leadership. We have completed more than 290,000 Galleri commercial tests. And it's important to recognize across that many tests that we are routinely finding deadly cancers in our population. So that's really important and incredible to see early on.
The value of the Galleri test is its ability to find cancers that aren't screened for today. And our biggest opportunity is deploying the test in a reimbursed environment to screening eligible asymptomatic patients, both in the U.S. and abroad. So there is nothing acceptable about the current status quo in screening today. The reality is that most deadly cancers are found too late. This is both a problem statement as well as an enormous opportunity, a public health opportunity at population scale. On the problem statement side, current screening is very limited. The reality is that 70% of cancer deaths are caused by cancers that we're not even looking for. There's no standard of care screening that's available. We also know that 86% of cancers are found not through recommended screenings, and that proportion is even higher when we get outside the United States.
On the opportunity side, we know there's a 4x improvement in survival rates when cancer is detected early in a localized state. So how do we capitalize on this opportunity? Through comprehensive research, GRAIL has confirmed that our Methylation Platform can identify a cancer signal that is shared across many types of cancer. This is the fundamental breakthrough that marks GRAIL's leadership in the field. The test is designed for use in asymptomatic populations to drive earlier detection of cancers and better outcomes. Abnormally methylated DNA is the hallmark of cancer, and additionally, it provides valuable information about where in the body that cancer signal is coming from. In other words, it can predict a cancer signal of origin. Galleri was designed to have a very low, very high specificity to limit false positives and to drive a high positive predictive value, a key clinical measure.
The technology has a number of other benefits, including a low clinical limit of detection and a cell-free DNA signal that preferentially detects highly shedding cancers that are typically aggressive. Our clinical implementation study, PATHFINDER , which was presented at ESMO 2022, showed that Galleri more than doubled the number of cancers identified when added to standard of care screening. We are very pleased that we are consistently demonstrating results across our observational and interventional studies. About half of the MCED detected cancers were early stage. About 7 in 10 of the MCED detected cancers had no other screening, standard of care screening available. The positive predictive value in the study population was 43%, which is an order of magnitude higher than those of the leading single cancer screens. As a reminder, PPV is among the most critical performance metrics for a successful MCED at population scale.
The localization accuracy of the cancer signal of origin was also high, leading to more efficient diagnostic workups. Galleri's cancer signal of origin is differentiating. The test is designed to be easily implemented into clinical practice, and the signal origin output allows us for a directed diagnostic evaluation. There were no serious adverse events in the diagnostic workups reported. And additionally, patient satisfaction scores were high, even among those with false positive results. Staying on the PPV we observed in PATHFINDER, it's important to note that we did not see any deterioration in performance as we advanced into real-world implementation. Our model PPV based on the case control study, CCGA, was 44%. And subsequently, in the implementation of PATHFINDER , we saw a PPV of 43%. So we are pleased that we continue to see demonstrated consistent results across our observational case control studies and our interventional studies.
We talked a few minutes ago about investments to scale. This includes significant investment in a new version of Galleri, which is both fully automated and integrated, meaning we've been able to eliminate numerous manual steps in the laboratory, allowing for greater efficiency and greater quality control. Updates also include reducing the panel to the most informative regions, allowing us to run four times the number of samples on a flow cell and reducing sequencing costs. We are transitioning to that new version of the test today and anticipate realizing the benefit from this investment as volumes grow over time. The implementation of these updates has substantially expanded our capacity, and no additional CapEx is expected to support several years of growth. We could begin shipping this version of the tests in December and expect to see COGS improvement as we scale.
The new test version also has an updated test report, which revises how the cancer signal of origin is classified to simplify the CSO to 18 regions and provide more valuable information to physicians. So the impact of cancer is enormous, both in terms of its human toll and its financial cost. Nearly every adult has a story about someone important to them that's been impacted by cancer. In fact, 19 million new cases of cancer occur globally every year, with resulting 10 million deaths. Cancer is currently the number two cause of death globally and is projected to become the number one killer. The ultimate opportunity for multi-cancer early detection is enormous. The total addressable market in the U.S. is over 100 million individuals. That TAM expands quickly when we bring in the U.K., where we're running the NHS Galleri trial of another 19 million of TAM.
In the E.U., we have about another 160 million people, and in Japan, close to another 50 million. So very enormous TAMs here. Galleri has found strong commercial reception in a largely pre-reimbursement market. We have already run over 290,000 Galleri commercial tests. In 2024, we completed approximately 137,000 tests. We currently have over 12,000 ordering providers. We also have seen repeat volumes moving higher over time. Today, more than 20% of the Galleri volume is repeat testing. The majority of that testing is from approximately a one-year cycle, and more than 70% of it is within 18 months. There is robust interest from providers and commercial partners. Our partnerships span health systems, employers, life insurance, and first responders. Our partners are also innovators, such as Function Health.
Function Health is a member-based consumer telemedicine provider focused on empowering patients to take control of their health by proactively monitoring for early indicators of disease. Galleri is offered as an add-on to Function Health's core testing menu at an additional cost, and we are seeing strong uptake with customers on the Function Health platform. Critically, Galleri is working in the real world. As you can see from this quote, our commercial use of Galleri is finding lethal cancers early in the real world, and in Tad Carper's case, head and neck cancer. Tad is the SVP of Communications for the Dallas Cowboys, and he had his story aired on the Thanksgiving Day Dallas Cowboys NFL game. The majority of these early-stage cancers do not have any screening tests, and remember that localized solid tumors have effective, often curable treatments, typically surgery with or without radiation.
We're immensely proud to be able to help patients and providers find these cancers early and enable positive outcomes for patients. So we have a strong financial profile. Revenues for full year 2024 are expected to be in the range of $124 million-$126 million, approximately 34% growth over 2023. U.S. Galleri sales are expected to be $107 million-$110 million, approximately 45% growth over 2023, and consistent with our narrowed expected range of 40%-50% up for the year. Our cash balance is $767 million. Runway provides runway into 2028, and we are well positioned as we head into our major milestones, including the readout of our registrational studies and the filing of our PMA. Full year cash burn for 2024 was $579 million.
Notably, we reduced our cash burn substantially during the year and achieved second-half cash burn of less than $200 million, which was below our guide of $220 million. Going forward, we will continue to invest in market development and are focused on obtaining reimbursement and broad access. The updated Galleri test, which we rolled out, will allow us to reduce COGS per test over time as we scale. Turning to the 2025 guidance, we expect our U.S. Galleri business to grow at 20%-30% in 2025. This reflects the reduced investment that we are making in commercial as we work towards achieving commercial spend neutrality and post restructuring that was done in August.
With a focus on efficiency and the completion of some of our larger research programs and infrastructure investments in 2025, we are projecting a cash burn of no more than $320 million, a significant reduction from our 2024. S o we have already built out our laboratory infrastructure to scale. Our Research Triangle Park, North Carolina facility is approximately 170,000 sq ft in total, enables us to scale lab capacity substantially with sufficient capacity to support multiple years of growth. As I mentioned, in our new test version, we've integrated significant automation, which supports large-scale testing and will drive costs down, and we have already demonstrated significant scale as we have run more than 600,000 Galleri commercial and research tests to date. So, stepping back for a moment, the longer-term vision for MCED is clear.
There is an enormous global market for people at elevated risk for cancer who would benefit from broad access to MCED. Many of our investments have been designed to meet that future with a high degree of capability, and that includes our new version of the assay that has a high degree of capability and has been designed for scalability and lower cost. Our commercial and medical affairs teams are educating physicians and health systems on how to effectively implement MCED into their practice, driving an understanding of how to effectively handle both positive and negative test results. All of this will help speed uptake with broad access. In the near term, we cross a number of key milestones in 2024, beginning with our separation from Illumina in June of last year and then proceeding across important goals towards our vision for population scale multi-cancer early detection.
Our key objectives are to deliver the first FDA-approved MCED test, achieve broad commercial reimbursement, and in 2025, we'll read out foundational data, including the early results from our 35,000 participant PATHFINDER 2 study, the first of two key registrational studies for GRAIL. We expect final data from the longitudinal 140,000 participant NHS-Galleri study, our second registrational study in 2026. With that, I'll answer any questions that people have.
Thanks, Bob. Really appreciate having you here today. If you have a question, please just raise your hand. We'll get you a microphone. Thank you.
Thank you. I'm a CFO of the health system, so that's my background. I also did participate in the Pathfinder trial. What I'm curious about is this isn't going to be a one-and-done test, presumably. So what is your thinking today as to how often that test should be reapplied to a population or to an individual?
Yeah, so right now, the best modeling we have is an annual test. So that's what the cycle is going to look like. It will be an annual testing pathway. Right now, as we mentioned, from a repeat test standpoint, we're seeing more than half of the people take it on approximately that annual cycle and about 70% taking it within an 18-month period. So those are usually not perfectly at 12 months, but that would be the intention.
Yeah, I'd just add, I mean, our NHS-Galleri study is a longitudinal three-year study, three time points. So when that reads out in 2026, you'll see, and we'll learn more about if a year is the right interval or not to see if you're finding cancers earlier rather than later.
Do you notify potential repeat customers that it's time to get another test?
We do. It depends on the channel. We have a number of different channels. So some we have much more direct access through the physician, and some we have more indirect access. So we often do, but we don't always.
What are your thoughts on some of the competitors increasingly moving towards the multi-cancer detection space?
Yeah, so it's actually good to see more and more people coming into the field. To this point, we haven't seen a lot of data. A lot of people are early on in the process. So we've been pushing ahead with our key registrational studies and driving towards PMA. But it's good to see other people with interest in the MCED space. It's certainly helpful. Here's a question.
Thank you. You are probably aware of that false negatives may be even a bigger problem than false positives. So you didn't deliver any data on the negative predictive value of the test. Can you comment on this?
Yeah, so certainly we're looking at tumor shedding DNA into the blood. And so what we've found is that typically the more aggressive cancers are shedding more DNA into the blood, and those are the ones that we detect. So a lot of physicians view it actually the fact that we preferentially find highly shedding cancers actually is a good thing, that the less aggressive cancers, indolent prostate, for example, cancers, we actually don't detect in that.
And so obviously you would like an ideal test. We believe that the positive predictive value, though, and the cancer yield from our test is quite high. And we've shown that in PATHFINDER, where we more than doubled the number of cancers of standard of care screening. So we obviously will continue to work to improve sensitivity over time, but we think where it is right now is a very, very useful test.
So NCI announced the Vanguard study selectees last week. Can you elaborate on why you were not selected for this study?
Yeah, so we chose not to participate in this study. As you saw in the presentation, we have our two key registrational studies across 175,000 people. We completed in July the study visit. So in the case of the NHS, we've gone through three years. As Aaron mentioned, the longitudinal study with them.
We're in the one-year follow-up, and we'll have the readouts of those in 2025 and 2026. We think the study is good. We think it's important for the earlier question for MCED developers who are probably earlier on in the process, and even the NCI talked about people in the earlier stages of development. We think it's well tuned to that. We've just progressed further than that.
Maybe turning to one from the webcast. How confident are you about the MCED bill passing this year?
I don't think anyone's ever going to predict what's going to happen in the government. What we can say, though, is we know it was in the bipartisan bill that was in front for a while, and so it did get to an agreement level, which is great to see. It will require a spending bill.
We've had multiple times now where the spending bill has been kicked down 90 days. So we are hopeful. We know we have bicameral bipartisan support. Both parties are behind dealing with cancer effectively. We think all the support is very strong. We're really looking for a bill that's capable of bringing it over. It's very difficult to predict the when, but we're confident it's set up as well as it can be.
Great. Maybe a follow-up for me on a different note, but could you talk to any impacts from the restructuring? Anything to note there?
Sure. It was a very substantial restructuring. It was about 35% of the people. What was amazing, really a shout-out to our team, is just the resilience of the company. Typically, when you have that level of restructuring, companies really suffer substantially.
And while people very much felt for the people in the organization, even people who were leaving, many of them came up to me and said, anything I can do to help push the GRAIL mission? The GRAIL mission is that strong that even people who had had to leave the organization were feeling strongly about it. And so I'm really proud of just the level of conviction, the level of mission-driven that the GRAIL team has demonstrated. And of course, there's some level of disruption, but the team has handled it really magnificently.
That's great to hear. Could you refresh where we are on an evidence pathway and timelines for FDA submission? Are you still on track for first half of 2026?
Yeah, so everything's geared towards first half of 2026. Again, our PATHFINDER 2 study of 35,000 people will be utilized for that. And the NHS-Galleri study, which is three years of 140,000 people, will be used for that. And we're in a modular submission right now with the FDA. We have breakthrough designation, and we expect the final module, the clinical validation, to be in the first half of 2026.
Great. Maybe just one final question from me, but just at a high level, how are you thinking about cash burn longer term and future financing needs?
Yeah, Aaron, maybe you want to take the cash burn one?
Yeah, definitely. So as you can see, as we executed our restructuring plan, we brought in the cash burn for the second half, where we thought we would have better than that, actually. And so the resilient employees, everybody just executed, and we were able to run the business as we'd planned.
We guided for next year, $320 million of cash burn, no more than that. And we will march toward that. And as we roll out the programs and complete development, we expect burn to decrease subsequently. And as Bob said, we see cash into 2028.
All right. Well, I think that's all our questions. So once again, thank you very much for being here. Real pleasure to have you. And thank you.