Ladies and gentlemen, please welcome the President of GRAIL, Dr. Josh Ofman.
All right, hello everybody. Good to see everybody. Thank you all so much for coming. We have a great day for you today, and hopefully many of you will also take our tour of the lab, which will be incredible. Again, it's a pleasure to be here. We're thrilled to host an Analyst Day. I think this is officially our first in-person real effort here, so it's terrific to have you all. We're going to go to a set of disclosures, which you're all familiar with. I won't—did I go too far? I won't read any of them, but just make sure if you have any questions about any of this, please come to us. Now I'm going to introduce our CEO, Bob Ragusa, who's going to give some introductory remarks.
Thanks, Josh, and thanks everyone for joining. Yeah, thanks everybody for joining us. I'm sorry I'm not able to make it there in person.
Uh-oh.
No?
There he is.
Can you hear me? Yeah, thanks, Josh, and thanks everybody for joining us today. I'm sorry I'm not able to join you.
Hold on one sec. Any chance we can hear Bob?
Open exchange?
There we go. Bob, up to you. Go for it.
Okay. Try it again. Thanks everyone for joining us today. I'm sorry I'm not able to join you there in person, but that does not diminish my excitement for you to be with the GRAIL team at our centralized lab in Research Triangle Park, North Carolina. I'd encourage you to spend time with our leaders and various experts in attendance and enjoy the guided tour of our lab. The lab is an operational hallmark in our endeavor for population-scale multi-cancer early detection.
Our goal today is to share with you key highlights of the business and the tremendous progress that we have made as a public company since June of last year. We will also provide access to some critical experts. These are the physicians who designed and ran our key studies and the physicians who are on the front lines today using the Galleri test with their patients.
We've got a very packed agenda. Aaron and Josh will go through a brief business review, followed by a review of PATHFINDER II results and the NHS study design and anticipated milestones by Dr. Nima Nabavizadeh and Professor Peter Sasieni. We will have a Q&A session at the end of the first section, take a very short break to provide lunch, and then we'll come right into the reviews of our international opportunity and the commercial business.
Finally, we'll close the formal presentation with a customer panel. At the end of the day, we'll also provide the opportunity for lab tours for those of you on site. We hope you find this an enriching day, and with that, I'll pass it over to Aaron and Josh for the business review.
Thank you, Bob. Thank you, Bob. Okay, everybody, thanks for—as Josh and Bob said. Thanks for coming out here. This is the first one of these that we've done. We'll be doing more of those in the future. I hope you can see, I mean, in a short 10 years, you have seen the data, you've seen the financials and all that stuff going on, but now you get to see the lab, you get to see the space where we're actually changing outcomes of cancer diagnoses.
We'll start here with looking at the financials and just kind of what we've done in this time period. We're focused on detecting cancer early when it can be cured. It's our mission. It's what we came up with the idea with nine years ago, almost 10 years ago, and we're marching down that trail. We've built something special here.
We're at the beginning of that, and we're really excited about where it's going. We see ourselves as a leader in this expansive field. We're first to market with an MCED test, launched in 2021. We've demonstrated performance through several studies, most recently the PATHFINDER II study, which you'll hear more about later today. We've built this large commercial experience, large clinical data set over that time period, and it really puts us in a position to continue to lead, and we're excited to be here.
Through the research studies and our clinical experience, this data set has allowed us to improve the test. It's allowed us to really show where this can go. The data sets that we've read out have just been phenomenal in our eyes. This opportunity is enormous, right? It's a huge space.
We're at the beginning of that, and we're really excited to see where this can go. As you can see here, we did $125 million in revenue in 2024. Through the nine months of 2025, we're growing at a 25% rate compared to last year. Again, early days, this is a pre-reimbursement space, as you'll hear more about our path to get to broader access, broad reimbursement, and so on from the rest of the team once I finish talking.
We've built this lab. We can run a million tests. You'll go see how automated that is. It's really impressive. It's one of my favorite things to go do at GRAIL, just walk through the lab and get a tour and see how it all works. It's really great. Most recently, we've managed to finance ourselves.
We announced a $325 million pipe, and that really gives us the capital to navigate with flexibility this ramp over the next three, four, five years. We're excited that with the investors that have come in in this time period, the partnerships that we've built and so on, it's really set us up well. Next slide.
Here's a little financial outlook. I always like slides like this where you can see revenues going up and to the right on one side and costs going down on the other side. We did a restructuring back in 2024, and since then, we've really managed to grow the business and execute against our milestones as we get to broad access while growing revenues. It's not easy, and this is a developing field.
With the financing that we've received, we now have the flexibility to adapt as the space grows, as we learn more about what's going to get to large adoption and so on. We've updated our guidance yesterday to be in the mid-range of the 20-30%, and we brought down our cash burn for the year to $290 million net of the financing fees for the year.
Again, continue to improve and perform well compared to how we thought we would. What we've been focused on in 2024 with this new platform is really driving COGS down. You'll see that on the next slide and give you a little more color on that. You see margins increased to 55% compared to the prior year of 41%. It's really driven by the new platform, variable cost and fixed cost improvement.
The way to think about the fixed cost is last quarter, we ran 66,000 tests, or an average run rate of 260,000 tests, somewhere in there. Compared to the prior year, it's about 160,000-180,000 test run rate on the older platform. Last quarter, we ran 45,000 tests. You can see just how much fixed cost leverage we have there.
We don't expect the clinical samples that we ran last quarter to repeat this quarter or in a subsequent quarter, but it's really an example to show how much fixed cost leverage we get once we put volume on this platform. Again, it can run a million samples based off the equipment that we have today and the space that we have, and then we can add to that modularly as the demand comes in in a pretty capital-efficient way. With that, I think I'm turning it over to Dr. Ofman.
All right, thank you, Aaron. Everybody hear me okay? Great. Now we're going to do a little kickoff into the real core of the meeting. Just to remind everybody why we're all here. We are here because cancer is soon to become the leading cause of death in men and women worldwide. Right now, it's cardiovascular disease that is expected to be overtaken by cancer either at the end of next year or the following year. It's one of the diseases that has touched all of us and our families. Is there anybody in the room who's not been touched personally by cancer? It's almost every room I go into, nobody raises their hand. It is one of those diseases that keeps people up at night.
The problem we're trying to solve at GRAIL is why is that? Why is cancer going to become the number one cause of death worldwide? It's because we're finding most cancer too late. We are here and dedicated to trying to solve that problem. We've begun this incredible journey with what I believe is one of the largest clinical genomics programs ever undertaken.
It began with our observational case-controlled study, which most of you are familiar with, what we call the Circulating Cell-free Genome Atlas. That was how we began to discover that we had a shared cancer signal that could be identified using methylation. We've used it to validate analytically our assay and then clinically validate our assay.
We have adapted our assay and learned a lot about the very nature of cancer through a biological signal that is being shed from cancers, and that is DNA being shed into the blood. What we learned here is that a methylation signature, a pattern of apparently methylated DNA, is very indicative of cancer. That pattern is almost never observed in people known not to have cancer.
That is when the light bulbs went off at GRAIL that we had a multi-cancer early detection test. In that methylation signature, we can also see a fingerprint of where in the body that cancer signal is coming from. That is the magic and the power of this assay. We have then studied it prospectively in interventional trials, the PATHFINDER study, PATHFINDER I, and PATHFINDER II around clinical performance.
We've put it into a randomized controlled study in the NHS, which you'll hear about, to define clinical utility. We're putting it now into a large prospective interventional real-world study in Medicare beneficiaries called the REACH trial. We only introduced Galleri clinically into clinical practice once we had validated the assay in an interventional study in patients actually being screened for cancer.
You may know there are other test developers now introducing tests into clinical practice based on case-controlled studies. We do not think that is appropriate, and it is probably not in the best interests of patients because you cannot define the effectiveness or safety profile of a product from a case-controlled study. It has to be used in a screening population prospectively in an interventional study. We have done that. I think we've set the right bar for evidence for the field.
This is a new field. If we want to change the paradigm of cancer detection, this is what's needed. You have to do it the right way. You have to build the evidence properly, and you have to introduce it clinically at the right moment when you've got the right level of validation and you understand both the effectiveness and safety profile of your product.
Now, again, we have shown consistently strong performance across a variety of studies. As you may know from working in diagnostics, which many of you do, it is very unusual to see the results of a case-controlled study be translated faithfully in an interventional study. Case-controlled studies, if any of you have read my blog post, can be designed in ways that can really determine the results that are observed.
When you see a case-controlled study being recapitulated in interventional studies, it's actually not that common to see that. What you've seen here with Galleri is across the PATHFINDER I study, the PATHFINDER II study, real-world studies, studies done at Mayo Clinic and Dana-Farber, our own commercial experience, you see a very consistent set of results related to what we think is one of the most important clinical measures of an MCED test, the positive predictive value.
Just so that all of you are reminded, PPV, positive predictive value, means if you have a positive test result, what is the likelihood that you're sitting there with cancer right then? Our PPV, you see, began being modeled from our observational study at about 44%, being recapitulated in PATHFINDER at about 43%. PATHFINDER II now, a larger, more diverse population at 62%. You see the other experiences.
What we've learned about our assay is that as providers have gained more experience, as providers understand how important it is to look hard for those cancer signals, you see the PPV going up. Mayo Clinic and Dana-Farber are good examples. They're slightly older populations, but what we know about these sites is they were looking hard for those cancers.
When they got a predicted signal that's in pancreas, ovary, liver, stomach, they did not stop looking and they found the cancer, and that's why their PPVs were so high. Again, consistent, strong results is the hallmark of a well-validated assay. I want to share a little bit about the opportunity of what we're talking about here before I hand it over to go through PATHFINDER II.
What we've done here on the left side of the slide is we modeled what does the world look like today? My belief is that if you want to really understand Galleri, you have to begin with an understanding of what is going on in the world today. Let's talk about that. The top row in burgundy there is what is happening in the world today. You have five screening tests today: breast, cervical, colon, lung, prostate.
They are finding 184,000 cancers every year in the United States. Pretty good, right? That's only about 14% of the incident cancers. In finding those 184,000 cancers, they are generating over 8 million false positives. Let me repeat that. To find 184,000 cancers, they are generating over 8 million false positives. In this country today, we are spending almost $40 billion a year on cancer screening.
Where do you suspect most of that money is being spent? Working up all those false positives. Not very efficient. That is about a signal-to-noise ratio of 1 - 44. Not particularly efficient. Now, those single cancer screening tests are great tests. They are saving lives. The deal we made with single cancer screening is that we have very high sensitivity and we accept very high false positive rates.
That is the deal we have made with single cancer screening tests. That would never be acceptable for a multi-cancer early detection test. We designed Galleri to be a complement to those single cancer screening tests. We cannot replace those. They are highly sensitive. They find early premalignant disease, and they are saving lives. Adding Galleri to standard of care screening is the right approach.
When you do that, you add an additional 482,000 cancers, additional 482,000, and you only generate another 380,000 false positives. That is modeled based on our data from clinical trials. If you look at this now, this new picture of what the screening system can look like, you can see that it is much more effective in cancer detection and much more efficient in cancer detection.
In fact, the signal-to-noise ratio gets driven down from 1 - 44 to about 1 - 14. The cost to detect a cancer gets reduced by about 65%. A much more effective and efficient system. This is the system that we are driving towards. This is the paradigm change we are proposing and are driving. On the right side of the slide is the fact that most of the cancers Galleri finds are currently unscreened.
There are no recommended screening tests for the majority of these cancers. Yes, we will find interval breast cancers. Yes, we have found and do find interval colorectal cancers. Yes, we will find aggressive prostate cancers. Standard of care screener are going to find the majority of those early cancers. What are we finding? The majority of what we find are cancers that currently have no screening today.
For those of you who may say, "You know, your overall sensitivity is not high enough," let me remind you that the current sensitivity for asymptomatic cancers, for cancers that have no screening tests, is effectively zero unless it is found incidentally. In other words, the false negative rate is almost 100% for the standard of care today. Okay?
That is now the picture that I want you to think about as you now hear the data coming from our PATHFINDER II study. We are now in our final push to complete our submissions to the FDA by Q1 of 2026. That submission, we believe Galleri will be the first FDA-approved MCED test. That is our goal. That has been our commitment. We are submitting PATHFINDER II data, which you are going to hear about in a moment.
We will submit performance data from the first 25,000, which was a pre-specified analysis with one-year follow-up. We will then submit the remaining 10,000 once that is completed. The NHS-Galleri test, we will be submitting the first year of the prevalence screening round and data from the intervention arm as part of our PMA.
There is a bridging study, which bridges the validation from our version that was used in those studies to the version that you're going to see on your tour of the lab, which will be our PMA device. We have a bridging study that will comprise the FDA submission, and we are looking forward to completing that in the first quarter of next year. Now, with that in mind, I want to very proudly introduce Nima Nabavizadeh from OHSU, who is one of our principal investigators in the PATHFINDER II study. Nima, the stage is yours. Thank you.
Thanks, Josh. All right. Hello, everybody. Thanks again for the invitation to be here. It really is my pleasure and privilege to be presenting the initial results of the PATHFINDER II study that we just presented at the European Society of Medical Oncology in Berlin about a month ago.
This study really is a landmark study that is really changing the way we're thinking about cancer screening. I'm a radiation oncologist at OHSU. I'm also a clinical researcher. We've had the privilege of collaborating with GRAIL for quite some time now on their prospective interventional studies from the PATHFINDER I study to the PATHFINDER II study and the currently occurring REACH study that we're also enrolling on.
I must say, we probably have one of the most robust experiences in the world in regards to providing these tests to participants and walking them through the diagnostic pathways for a signal positive. We've enrolled nearly 8,000 participants on a multitude of these studies. Again, it's a pleasure to be here, and I hope I have some insights to offer. Here are my disclosures.
Just jumping right into it, the PATHFINDER II study is the largest interventional MCED study ever conducted in the United States, enrolling nearly 35,000 participants across 32 North American healthcare systems, OHSU being one of them, over 32 months. All participants in the PATHFINDER II study were at least the age of 50, with no clinical suspicion of cancer nor diagnosis of cancer or treatment of cancer within the last three years. All participants had their blood drawn.
The MCED test was performed, and they were provided with the results. For the participants who had a cancer signal detected, further diagnostic evaluation ensued by the study team. The investigators were provided with protocol-recommended guidelines for diagnostic workup targeted to the cancer signal origin that the Galleri test had predicted.
The PATHFINDER II study will be following all of these patients for three years to assess their cancer status, as well as any patient-reported outcomes, such as adherence to recommended screening guidelines. The primary objective of the PATHFINDER II study was to evaluate the safety and performance of the Galleri test in a large and diverse intended use population. With this pre-specified initial analysis, we analyzed 25,000 participants on the PATHFINDER II study who had at least one year, 12 months of follow-up. The table to the right shows the baseline demographics of the study.
A large and representative population was enrolled on the study across age, sex, race, and ethnicity. This was largely due to outreach efforts and recruitment strategies. We believe that this is really important to assess the utility of this test in an intended use population. 216 participants were found to have a cancer signal for a cancer signal detection rate of 0.93%. For those participants with positive signals, the positive predictive value was 62%, meaning 6 out of 10 participants with a cancer signal were ultimately identified to have a cancer.
This PPV is higher than what's been previously seen with the Galleri study, and it's orders of magnitude higher than the PPVs of our current single cancer screening methodologies, such as mammogram or FIT testing for colorectal cancer, which have PPVs of around 5%, meaning that for patients with positive results, only 1 in 20 are found to have a cancer. Josh alluded to the high burden of false positives there.
The specificity of the Galleri test on the PATHFINDER II study was 99.6%, which is consistent with previous reports of the Galleri test. This was intentional. This was intentional to minimize the number of false positives, thereby driving the high PPV that you're seeing there. I agree, and I know GRAIL agrees, that this is important for safe population screening. I'll pause. We're going to want black on the screens, but I can keep talking.
My screen here. All right, there we go. Can we go back one slide? There we go. Specificity was high. For interventional studies like the PATHFINDER II study, it is not known at the time of testing whether or not a participant has cancer. Thus, we calculate the episode sensitivity, which is a measure of a test to identify cancers within a pre-specified time frame, and in this case, 12 months.
The episode sensitivity for all cancers across 18 broad cancer types was 40.4%. This episode sensitivity was even higher in clinically relevant subgroups. For the 12 cancers responsible for two-thirds of U.S. cancer deaths, episode sensitivity was 74%. It was 72% for six aggressive cancers with low five-year survival, 56% for all cancers except breast and prostate, and 55% for cancers without common screening options.
Again, I want to remind folks that comparing episode sensitivity, one should not compare episode sensitivity from interventional studies like the MCED study to test sensitivity from case-control studies, as they're designed completely differently. Within the one-year time frame of this initial analysis, 329 participants were diagnosed with a cancer. Two hundred of them, or 61%, were screen-detected, far higher than the currently 14% of U.S. cancers that are screen-detected. The MCED test detected 133 cancers.
The MCED test identified seven-fold more cancers when considering the cancers that were screen-detected through single cancer screening methods of breast cancer, cervical cancer, colorectal, or lung cancer. When also considering the 47 screen-detected prostate cancers, the MCED test increased the number of screen-detected cancers by threefold. Cancers identified on the PATHFINDER II study were clinically relevant.
114 were new primaries, 18 were recurrent cancers, and one participant had a cancer of unknown primary site. Two-thirds of these MCED-detected cancers do not have recommended screening. Furthermore, most cancers that were identified were in early stages. 69% were between stage one and three, 54% between stage one and two.
Of these early-stage stage one and two cancers, 74% of them do not have recommended screening strategies. One concern with MCED testing is the fear of a diagnostic odyssey, particularly if a test does not provide a cancer signal origin to help guide diagnostic workup. The PATHFINDER II study showed an accuracy of prediction for the cancer signal origin, 92% for true positives.
This accurate cancer signal origin helped guide efficient and targeted diagnostic workup, with the median days of diagnostic resolution after a positive signal being 46 days for all participants, 36 days for true positives, and 75 days for false positives. Another fear with MCED testing is a fear of too many invasive procedures. We found this fear unfounded as well. Of the 25,000 participants who received an MCED test, less than 1%, 0.6%, had an invasive procedure due to a positive MCED test result.
Participants that did not have cancer had far fewer invasive procedures. At the time of initial analysis, there have been no serious study-related adverse events reported during the diagnostic workup. In summary, these initial PATHFINDER II results demonstrate robust performance and safety across a broad population. It is the largest interventional MCED study conducted in the U.S. to date.
Increased the number of cancers detected by screening by more than seven-fold when added to recommended screening. Demonstrated robust performance with a 62% positive predictive value, substantially higher than observed in prior clinical studies. The majority of the cancers that were identified were early-stage. The majority of those cancers do not have recommended screening strategies. The test also enabled prompt, efficient diagnostic resolution with a favorable safety profile.
I believe these results really illustrate Galleri's clinical utility and potential to improve outcomes in an intended use population. I think we have a Q&A session after this. I'm happy to answer questions. Thank you all. I'll be, yeah, I should introduce our next speaker, Professor Sasieni, who is from the U.K., who is an instrumental lead in the NHS-Galleri study that we're anxiously awaiting. Thank you, Peter.
Thank you. Thanks, Nima. Thank you very much. It's a pleasure to be here. My disclosures, I'm on the Scientific Advisory Board for GRAIL, and I should perhaps say that I'm not a physician. You've heard a little bit about the CCGA, the SYMPLIFY study, which I don't think you have heard about, and PATHFINDER II. I just want to say a little bit about these before talking about the NHS-Galleri study.
The CCGA really was a very large case-controlled study, which provided data on the ability of the test to detect and locate multiple types of cancer, and then also to demonstrate that a positive test result was extremely rare in people without cancer. That was done in taking a large number of people with cancers before they were treated, but after diagnosis, and a large number of people without cancer.
The SYMPLIFY study, which was done in the U.K., was done in people who were referred for diagnostic workup because of symptoms that their doctor felt were likely to be due to cancer. Only about 7% of those people actually had cancer. Nevertheless, the test was done. The results were not disclosed, so actually mostly the sample was taken, but the test was not analyzed for some time.
The results showed that actually, if you have a positive result, indeed, the chance that you had cancer is extremely high. These were symptomatic people. It was much higher than you saw in PATHFINDER II. The other thing, which the new results from SYMPLIFY showed, was that the people who had a positive test result but no cancer was found initially, over the next two years, a third of them had a cancer diagnosed.
PATHFINDER II, as you've heard, shows that you can actually detect cancers before symptoms are found using this test. These were people who were coming for screening, and it showed that you really do find cancers and that there were no safety concerns whatsoever. All these studies, if you like, showing that the test does what it says on the can, there's nothing to say that there's really a good advantage of having the test done.
That's what we wanted to set out in NHS-Galleri, that not only can we detect and locate multiple types of cancer, but by doing that, there is some benefit to the individuals. If you like, the first three studies are all to do with clinical validity, whereas the other one is really the utility.
Is there an advantage to you of having your cancer found early by going for screening? NHS-Galleri is being done in England, possibly because we say that the lifetime risk of cancer in England is one in two, not one in three. I think that's probably just because we calculate things a little bit differently. Cancer rates are very similar in the U.S. and in the U.K., with a few exceptions. It's a very large study, 140,000 people. I was a graduate student at UW. The Husky Stadium takes 70,000 people. That's the number we've got in each arm of NHS-Galleri. I think a lot of you are from New York. I think 140,000 is like three times the capacity of the Yankee Stadium.
We wanted to make sure that we could compare actually what happens if you have the test and if you do not have the test. All 140,000 people had a blood sample collected, and we only randomized them once we had that blood sample. They were randomized to analyzing the blood sample or storing it for future work. Half the people, 70,000, have had their test screened. If it was positive, our team called them up so that the samples were all analyzed here in the States, some of them here, some of them in California. The results were got back mostly within two weeks. We phoned the people up to tell them about the positive result and made an appointment for them to go to an appropriate clinic straight away.
All individuals, so we didn't tell people which arm they were in unless we phoned them up to say you've had a positive test. All individuals were then invited back for a second blood sample at 12 months and a third blood sample at 24 months. In that way, this study is going to be able to tell you a lot about the performance of the test, not only when you first do it, but also on a subsequent test. It's what we call an incident screening round. If you saw in PATHFINDER II, there were quite a lot of stage four cancers found initially on screening. I really hope that there'll be far fewer found at 12 months and 24 months. This will give you very large amounts of data to look at the performance of the test in that way.
It also means that we can compare what's going on in the two arms. Is it true that the people who are screened are less likely to get an advanced stage cancer, stage three and stage four cancer, than those that were not screened? If we can do that, it's stage three and stage four cancers that mostly are what kill people of cancer. Most stage one and stage two can be cured. If we can shift that, we will really be doing something very useful. You can be sure that screening with this test annually is a good thing. I want to talk about the timelines of the trial for a moment. We promised GRAIL that we would start recruiting in August 2021. My team were not so happy. They thought there were all sorts of problems.
We recruited a few people on the 31st of August 2021. In September, we sorted out all the teething problems, and we recruited 140,000 people in 10 and a half months. That is the fastest recruiting clinical trial since the SALT vaccine trial in 1954. I've said that a few times. No one has corrected me, so I think it's probably true. We collected blood samples at 12 and 24 months. The last of the blood samples was collected in July last year. The main analysis that we hope to publish next year is on cancers diagnosed up to July of this year. It takes some extra months because cancer registration doesn't happen instantly. In fact, it's incredible that we're going to get results within about six months. That is a quarter of the time that it would take typically.
The cancer registry has been trying to get to two years, and often it's been three years before they've been able to publish results saying we've got complete data on cancer. It takes a long time for the data to get from the hospitals to the registry and to be cleaned. There will then be two other waves of publication. The individuals in the study will be followed up for mortality. Did they die? What did they die of? Two years beyond that time, and then a further three years. It will be six years from the last person having an appointment in the trial or eight years from when they were last randomized. The main endpoint is a reduction in advanced stage cancer. This is a little bit controversial, so I want to talk about it a little bit.
The first is that I think it's really important to think about causal reasoning. Much of my career, I worked on cervical cancer, HPV vaccination. I want to talk about that for a minute. We now know that cervical cancer is caused by HPV infection. If you have a persistent infection, it can start to lead to a precancerous lesion, cervical neoplasia. If that's not treated, it can go on and become invasive cervical cancer. If you had a cervical cancer and you did not treat it, or even if you did, you can get death from cervical cancer. If you can prevent the infection, you'll be able to prevent the death from cervical cancer. No one said that you had to wait and show a reduction in mortality from cervical cancer in order to introduce HPV vaccination.
In fact, it was only 17, no, slightly less, about 15 years after we introduced HPV vaccination that we were able to show a reduction in cervical cancer as a result of that vaccination. Similar arguments go for cancer screening. Cancer progresses through stages. For most cancers, prognosis gets substantially worse for the more advanced stages. If you find a cancer earlier, screening will lead to fewer advanced stage cancers.
Because the advanced stage cancers have substantially worse prognosis, you are going to likely to reduce cancer-specific mortality. What data that exists shows that this is true. These are meta-analyses. Each dot on these graphs corresponds to a different randomized controlled trial comparing screening to no screening, different types of cancer screening. On the vertical axis, it is the relative reduction in cancer mortality. On the horizontal axis, it is the relative reduction in advanced stage cancers.
You can see that the results are highly correlated. Virtually everything is either in the top right saying that screening worked on both measures or the bottom left that it really did not work. There is a second paper which had more studies in it showing that. If you reduce late stage cancer, it makes causal sense that is going to result in a reduction in advanced stage.
If you wanted to look at mortality, we are going to have to wait longer, and we would have to screen more people. The study would probably have had to be 50% larger to last twice as long, and we would have no results for a long time. In that period of time, you could be making a lot of progress in terms of rolling out screening if it works.
This graph, which is from the same sorts of studies, but here there is one dot for each type of screening. Each one is a meta-analysis of that type of screening. This is the significance. You can see that if the results were not significant for a reduction in late stage, they were not significant for a reduction in mortality. If they were significant, they were significant for both, with one exception, and that was in liver cancer, where at the time these studies were done, everyone who got liver cancer, even if they were diagnosed stage one, died from liver cancer. How are we doing this? First of all, we are going to test for a reduction in stage three and stage four cancers from these 12 pre-specified cancers that account for two-thirds of cancer mortality in the U.S. and the U.K.
If that's significant, the result's significant. The trial has shown that it can reduce advanced stage cancers from these 12 types. If it is, we want to look further. Does it have an effect on other types, other than 12 types, or does it have an effect overall? We can do additional testing, first looking at everything other than prostate cancer, then everything including prostate cancer.
Because we're doing this sequential testing, we're only going to do the test if the test before is significant. There's no problem with multiple testing. There are lots of secondary objectives. Some of the key ones is to see if there's a reduction in stage four cancers, which are the most deadly cancers. We also want to look at the test performance.
There will be 10 times as much data from this trial than there has been so far from PATHFINDER II in terms of test performance. It really is a massive study. We'll look at the overall cancer detection rate. It's not important, if you like, that the sensitivity is poor compared to other screening tests because it's screening for lots of cancers at once. What's important is how many cancers you're finding, how many cancer deaths you will be preventing for every 100,000 people you screen.
We'll be looking at safety. Important. We're not expecting any adverse safety signals, but it's really important to demonstrate that at scale, this is safe. Healthcare utilization. What actually happens? How many tests are we having to do in all these people who are going to be testing positive? We'll be eventually comparing cancer-specific mortality between arms.
In terms of cancer-specific mortality, hopefully towards the end of next year, we should be able to look at predicted mortality, which is sort of saying, based on the cancers that we have diagnosed, the stage that they were at, what do we think about when those individuals might die from cancer? We'll then, in two years' time, two years later, look at the actual mortality on a nested analysis, which gives us far more precision in able to look at that. Three years after that, we'll look at the observed mortality in the whole cohort. Thank you very much.
Sorry. Okay. Thanks very much, Peter. My name's Harpal Kumar, for those of you I haven't met. Great to see you all here. We have time now, about 15 minutes for any questions that anyone has. Yeah, straight over here. Right. There's a roving mic, so if you just wait till the mic gets to you for any of our four speakers so far. Someone get home. I wrote pair of tennis shoes.
Here you go. I'm Subbu Nambi from Guggenheim. This question is for Professor Sasieni. You articulated the endpoints on the NHS trial on slide 36, basically the primary endpoints. Is this how the FDA will also look at this study?
Does someone else want to answer that? Let me take a stab at that. The FDA has been pretty clear in their several advisory boards. They are not looking at mortality. The FDA is going to be looking at what they call clinical validation, clinical performance. That's why in our submission, we're just submitting the data that we have now, which is the prevalent screening round from NHS-Galleri.
They are on record saying mortality is not anything that they're looking at. Clinical utility typically is not something that the FDA looks at for approval. They're really looking at clinical validation. Got it. Thank you for that, Josh. Sure. Josh, could the SYMPLIFY trial data, which was presented at ESMO, be sufficient to be a supplemental to existing PMA so you get approved as a diagnostic test for symptomatic patients? It's a terrific question. We talk about that often.
Remember, and maybe Harpal, you're better to answer this, it was an observational study. What our thinking is, is that should we decide to pursue that, which is a good idea, we would likely need to do an actual prospective study in that population. Because remember, as Dr. Sasieni mentioned, we did not return results in that particular study, but the results are quite compelling.
Perfect. Thank you. Bob. Sure.
Okay. I saw lots of other hands. Can you just put them up again right next to us, and then I'll come to you two.
Good morning. This is Doug Shankle from Wolfe Research. Thank you guys for doing this. Great day, great plan. Actually, let me build off of Subu's question on SYMPLIFY. I remember being part of the pre-IPO process and you guys actually having a product in the pipeline called DAC. I should be able to, off the top of my head, remember what that acronym was for. Essentially, that's essentially what I think SYMPLIFY is getting at. The follow-up question to Subu is, I think we need to think of that as, and just correct me if I'm wrong, but that's where you really want more of a rule-out test rather than a rule-in.
Again, I want to make sure I'm thinking about it correctly. If I am, from a negative predictive value standpoint, which I think would be the more important metric, I think there were studies that showed 97% and 99%. I think SYMPLIFY was in that range. Is that high enough for that population?
Shall I take this one? Yeah. Doug, thank you. Largely remembered very well, DAC stands for diagnostic aid for cancer. What we did in SYMPLIFY was we looked at patients being referred to a number of different types of clinic based on what their primary care physician suspected was the type of cancer that they had. Your memory is extremely good.
Just to boil it down, the best performance in terms of negative predictive value was in patients suspected of having upper GI cancers, so liver, pancreas, stomach, esophagus, and so on. There, the negative predictive value was 99.1%. That is probably good enough as a rule-out test, given that the background incidence of cancer in that population is higher than that. That is exactly what we want to sort of test further in a prospective interventional study, as Josh referred to just there. It was lower in some of the other types of clinics.
Again, that was an observational study, and we would want to test that in an interventional way. What's really important is that a large number of patients who are suspected of having cancer have very non-specific symptoms. These might be things like unexplained weight loss or abdominal pain.
It can be very difficult for primary care physicians to know which clinic to send them to because it could be several different types of cancer, or it could not be cancer at all. Often, that initial choice of clinic turns out to be wrong. That is how patients end up going through a diagnostic odyssey and taking a long time to get diagnosed. There is a real opportunity there that we want to explore.
Maybe just two more points on this. The CSO predictive capability of Galleri in this setting is uniquely important because, as Harpal said, it's almost impossible to know to send them to the OB-GYN clinic or the GI clinic, what to get worked up. Even those false positives that were then converted to true positives, the CSO was right almost every time.
There was like one exception, I think. There was one patient. The other thing I'll point out to you about negative predictive value, it was very high in the SYMPLIFY trial. It was just as high in PATHFINDER II. Okay? Negative predictive value was 99%. That's, I think, critically important to get the right balance of sensitivity and specificity, PPV and NPV.
If you'll indulge me a little bit more on this, that was all super helpful. I understand. I mean, ultimately, the vision for the company is getting through the FDA, getting CMS reimbursement, and having this as a test that's available broadly amongst the population you talked about. At the same time, there's a limit to what you can control there, right? I mean, you're doing all you can do from a study standpoint. You're going through the FDA.
You're still waiting for congressional action to actually put you in a position where you could get reimbursed broadly. With that in mind, when I think about SYMPLIFY, when I think about, Josh, what you just said about what you saw in PATHFINDER when it came to symptomatic patients and how the study, how the assay performed there, when you looked at the detection rate of patients who once or individuals who once were patients and had cancer, there is a very good argument for this assay in a more symptomatic population or a population that is at higher risk. Either they had cancer before or they had hepatitis, so they're at heightened risk for liver, or dense breast women who really can't benefit from mammography. If we think of I could go on, but I won't, and I've talked a lot already.
My question is, are there alternative paths to reimbursement? From CMS, I could see where this goes from being seen as a screen to more of a surveillance tool, which might allow you to get reimbursed as an LCD. I've heard about some self-insured employers looking at this as an attractive way to earlier detect cancer in higher-risk self-identifying populations. I just might be wrong. If not, am I thinking about this, thinking about things that could give you alternative paths to getting paid?
Yeah. It's a great point. Let me take a stab at it and jump in. I think in the United States, you've correctly identified the challenges with current getting to broad reimbursement. There are alternatives. We've looked at the alternative around surveillance, and it's not quite so certain. We've explored that directly with MOLDI-X and others.
There is a lot of uncertainty around that as well. If it was so clear, I think we might have thought about it a little bit differently. We do know, as a diagnostic test, there are clear pathways through MOLDI-X that are not available for screening. We have contemplated that. We definitely made a very conscious decision at the time of the spin to get very focused on Galleri. That took all the company's resources to get where we are today. As we emerge from that effort, we are looking at these other opportunities very carefully. Harpal is leading our charge, really, in looking at that symptomatic population. Just to clarify one thing you said, we did not have symptomatic people in PATHFINDER II.
I was just pointing out to the high NPV in asymptomatic screening, which I think is we're making the same point, that that's really high even there. There are opportunities in the symptomatic. We do know it is being used in that population by doctors today. These other high-risk populations, people with prior viral infections, people with prior cancers, are elevated risk groups that should have access to Galleri as a screening test. Whether we do surveillance or diagnostic in them, I think, is yet to come. Stay tuned.
I want to make sure we get some more questions in because there are lots of other hands up. Yes, over here. Yeah. Yes.
Oh, yeah. Thank you. This is David Westenberg at Piper Sandler. Just on the positive predictive value, can you talk about the time that elapsed from a positive diagnosis on GRAIL to a, I'd say, ground-truth positive? Is there a way, if you found that maybe you are finding cancers a little bit later, is there a way to write in a supplement or submit a supplement to the FDA if that winds up being the case?
So Nima d o you want to ta ke that first?
Yeah. I think you're speaking to the metric of the time to diagnostic resolution. We call diagnostic resolution a time point whenever the investigator feels that we've exhausted all of our methods of trying to find a cancer. For all patients, it was 46 days. It was faster for true positive patients. An example is somebody with a hepatobiliary signal.
You get a CT scan, you almost immediately see a cancer, and you call it pretty quickly. Whereas false positives were longer than that because you're going down the next-step pathways of trying to find a cancer. Certainly, I think there's an element of us looking harder now because PATHFINDER I, with the high PPV, kind of encouraged us to maybe not set aside some indeterminate imaging finding, but to kind of aggressively pursue it. Many times, in my experience, uncovered novel cancers. Yeah, I mean, I guess the second part of your question was?
It was related to the FDA. Can you repeat that part of your? I was going to ask if you found cancer, say, later in some of the submission data, like two years later, they come up with a cancer or anything like that.
Yeah. That didn't happen. What we're referring to in the SYMPLIFY study was in symptomatic individuals, which is not our PMA submission to the FDA. In symptomatic individuals, when we looked at those false positives and followed them for two years more, I'll let Dr. Sasieni comment on this.
It is worth saying, in PATHFINDER II, we are going to be following up all of those patients for a further couple of years. We will know if the same thing happens, what we've seen in SYMPLIFY, whether the same thing happens in PATHFINDER II patients. The suspicion is, yes, that is going to be the case, but we do not have that data yet. It will not be part of the PMA submission right now. To Harpal's point, we are going to learn a lot about that over the next two years of follow-up.
I'll just ask one little follow-up to that. I will not ask my second question given the time. Just in terms of, I believe your policy is to run a second Galleri test when you do have a false positive. Can you talk about what results or the statistics that you found when you ran that second Galleri test, whether you've seen positive predictive value and negative predictive value improve on that second one or not? Thank you.
What we can say, and jump in, anybody who knows, in commercial practice today in the United States, if a doctor, and we'll ask our doctors on the next panel, if you get a positive Galleri test and you do a workup and it's unrevealing, rather than suggest whole-body imaging or ask you to just give up, we actually offer a free repeat Galleri test.
In that setting, if those repeat Galleri tests are negative, we have found almost very few instances where those individuals end up being diagnosed with cancer. We do not have enough sample size to compute a valid negative predictive value yet, but it is very high. Similarly, when that second Galleri test comes back positive again, they are most often found to have cancer. I will just give you an anecdote to what Nima just said. We have gotten several phone calls.
I get these phone calls from doctors who have had positive pancreatic signal, or the two that are the most common, and they have ill-defined imaging findings, subtle inflammatory changes in the pancreas, for example. I get called saying, "Hey, should we give up?" My answer is usually, "No, do not give up." They do an endoscopic ultrasound.
In the two cases that have just most recently happened, they found head of the pancreas tumors in both of them. If you get another positive signal, it is very likely they have cancer. If you do two tests back to back, do you cut the false positive rate in half, or how much do you change? Yes. The false positive rate gets cut. I can't give you the exact statistics, but it almost eliminates if there's another positive signal, it takes the false positive rate way down.
Over here.
Hi, this is Alex Vukasin on behalf of Kyle Mixon, Canaccord Genuity . Thank you for taking our questions. Aaron, just two on the business generally. To start, what will the impact of discounting be on ASP going forward? Thanks.
Yeah. We've got a list price of $949, and we discount down from that based off of volumes. As we get more and more large physicians' practices or digital health platforms that are offering the test, they'll hit higher volume tiers, and the test price will come down. We're prepared for the test price to come down. If you look at the CMS legislation, it reimburses at around $500 a test.
We built this platform to be able to accommodate that. We're prepared for that. How rapidly that changes will really be driven by how fast uptake is with our current pricing scheme. Got it.
One more quick one from me. In a perfect world, the NHS study is successful. It enables widespread adoption across the geography. My question would be, provided the study is ultimately successful, would a strategy of leveraging other national health organizations to run studies of a similar fashion become an essential part of the adoption strategy going forward, or is something of that nature already in the works or front of mind? Thanks.
Yeah, why do not I take that one? We do not think we are going to need to replicate something like the NHS-Galleri study in other countries. If you look at any new medical innovation, you tend to have one major pivotal registrational study. We have actually got a couple of registrational studies. You do not need to repeat them in other countries. Some countries do want to have smaller local studies done, really, to test it in their population. Usually, that is for reimbursement purposes. Sometimes it is for regulatory purposes. Those are typically much smaller. They're not big randomized studies of the sort of nature that we've been talking about for NHS Galleri.
Okay. We're going to have to cut it there, I'm afraid, for time. We now have 10 minutes, I believe. I'm looking at Alex at the back. Yes. Where you can grab your lunch, go to the restroom if you need to, and then we'll start again in 10 minutes. The lunch is right back here, behind this wall. Right here. Thank you, everyone.
Ladies and gentlemen, please welcome back to the stage Sir Harpal Kumar.
Okay. Thank you, everyone, for coming back promptly. I hope everyone's managed to get some lunch. Please do carry on eating while we're talking. We're going to move into more of a commercial section now. I'm very briefly going to cover some comments on the international opportunity, and then Andy Partridge will talk about some of our experience in the U.S. so far.
On the international opportunity, many of you will have seen this slide before, and Josh alluded to it earlier. Cancer is a huge global problem. We talked about the fact that it's the number two cause of death currently around the world with the latest statistics. More than 10 million people are diagnosed every year. To give you some context about what's coming, in the next 15 years, that's projected to grow to nearly 29 million incident cases every year. Sorry, 19 million currently, projected to grow to 29 million in 15 years. About a 50% increase in the next 15 years, and it's going to continue growing thereafter. These are World Health Organization projections.
For those of you who are more interested in the U.S., the projection is that by 2040, cancer cases are going to grow by more than a third from where they are today. The numbers are growing really very, very rapidly. We are, as I just touched on, we see this as a huge global opportunity and one where we want to bring this technology to bear on participants, individuals right across the world, not just in the U.S. or U.K. The numbers are staggering. We see, as you'll have seen before, the opportunity in the U.S. is a town of about 100 million people. If you add in the EU, U.K., and Japan to that, it takes it up to about 300 million people. Of course, there are many, many other countries besides that. There's all of Asia, there's all of Africa, and so on.
This is really an extraordinary both opportunity, but also challenge given the tsunami of cancer cases we have coming our way. What have we been doing? We've really been focused in the short term on identifying partners we can work with in specific countries where we can rely on their local expertise and infrastructure to bring Galleri to their populations. At the moment, while we're in this largely pre-reimbursement phase in the U.S., we're looking for ways in which we can do that in a very resource and capital-efficient way. In other words, not having to embark on building a lot of sales and marketing infrastructure in those countries, but, as I say, identifying partners that we can work with. Where are we today? We've launched in a few countries around the world.
We launched in Israel just about 10 months ago, 10 or 11 months ago. We announced just a few weeks ago that we've launched in Canada. Sorry, Israel is with a partner called Oncotest. Canada is with a partner called MedCan. Obviously, in the U.K., we also have our partnership with the NHS, where pending results from NHS Galleri next year, we hope to have conversations about moving that forward. As you know, a few weeks ago, we also announced a collaboration with Samsung to bring Galleri to Asia, starting in South Korea and hopefully expanding thereafter to Japan and Singapore. These are all very substantial market opportunities. As I say, we're relying on our partner to be able to bring Galleri to those individuals in those countries for now.
Of course, there's a big wide open space in terms of countries we have not yet launched in. I will just tell you, and perhaps this is no surprise, I'm getting calls from pretty much every country around the world on a pretty regular basis about how we can bring Galleri to those countries. The challenge at the moment is finding the right partner to work with in those countries. We are having many very interesting and encouraging conversations, so continue to watch this space. Just a couple more words on the Samsung collaboration, which we announced a few weeks ago. This will be Samsung developing an infrastructure to bring the Galleri test to individuals in South Korea, as I say, possibly extending thereafter to Japan and Singapore. At the outset, those tests will be performed here in RTP.
We're also going to be exploring some potential opportunities to collaborate with Samsung Electronics, which has a very wide array of interests in healthcare and medical technologies more generally. Those conversations have not started yet, but there are some potentially interesting avenues that we want to explore with them. Also, as you know, between the Samsung Holding Company and Samsung Electronics, they will be investing $110 million into GRAIL, subject to us finalizing the closing conditions that we have told you about.
A really exciting collaboration that we are moving forward. Just to give you a quick insight into some of what we are doing internationally. With that, I am going to hand over to Andy Partridge, our Chief Commercial Officer, who is going to tell you about our U.S. experience.
Thanks so much, Harpal. It is an incredibly exciting time to be in the commercial organization at GRAIL. I really do believe we've got a tiger by the tail with the Galleri test. We have a huge unmet need for cancer screening, a large addressable population worldwide, and best-in-class product performance with Galleri. We're detecting cancers every single day. Many of them early stage.
Those of you who are here with us in Raleigh can see all of the posters throughout our laboratory here of patients that we picked up with early-stage cancer due to the Galleri test. We're also years ahead of other companies in terms of the expansive clinical evidence generation program that we've embarked upon, which is now reading out, generating excitement with our customers and building palpable momentum for us. We're also a long way ahead in terms of the partnerships that we've developed over the last three years.
We have two upcoming milestones that are going to generate additional customer confidence and excitement with the PMA submission and ultimate FDA approval and the readout of our NHS-Galleri study. We're continuing to drive volume. 26% growth year over year that we reported yesterday for Q3. That's driven by growth in our provider channel, which was 37%.
That growth is due to increases in both breadth and depth of prescribing. So far this year, we've added almost 3,000 new prescribers for Galleri. We've also increased the depth of prescribing for those prescribers by 20%. The drivers of the increases in depth have been repeat testing, contracting and discounting, targeted media, and new customers that we've added. In terms of repeat testing, we're now seeing 29% of our volume is from repeat tests.
It is exciting because some of these repeat tests with patients who are on the second or third year now of Galleri testing after they had no cancer signal detected in the first or second year, are now seeing cancer signal detected in those subsequent years that end up with earlier stage cancer detection, increasing physician confidence even more about the Galleri test. In terms of volume, we've done about 40,000 tests over the last 12 months, which were repeat tests. Also, our electronic order integrations have increased the depth of prescribing as well with partners such as Quest and Athenahealth.
Year to date, since we've moved forward with a number of these integrations, we've had about 13,000 tests go through these new electronic integrations, which is essentially an easy button for physicians as we've now incorporated Galleri into the workflow that they have every single day, making it much easier to prescribe Galleri. We've seen a number of benefits from that.
We have about 1,000 providers now that have prescribed through either the Quest or Athena integration. These integrations have led to new providers coming on board. Over 300 of those 1,000 providers were new prescribers for Galleri. Those were physicians that did not want to prescribe until we actually built Galleri into their regular work order flow. We've also seen an increase in prescribing.
For those prescribers who were already using Galleri after the electronic order integrations, we've seen an increase in the depth of prescribing from these prescribers. Initially a big bump, which then plateaued down, which is a meaningful increase post-electronic order integration. We've also seen improvements in efficiency. Improvements in efficiency, as you see from Quest, with things like kit list shipping, bulk order, that's improving our efficiency. The electronic order integration has reduced accessioning issues.
With paper orders, we see a higher accessioning issue rate, which takes our customer service team time to resolve those. With these integrations now, that's significantly reduced those accessioning issues. With Rocuro Health, that's our telemedicine partner. They support orders coming through on galleri.com, and they also support many of our enterprise clients as well. Rocuro Health has proven to be a very reliable partner for us.
We're also the leader in digital health. This is part of our overall market access strategy. Longer term, we're focused on securing broad public and commercial reimbursement, focused on Medicare through the legislation. Shorter term, your digital health with access to large patient populations who are health-focused and cash pay through partners like Function Health and Everlywell give us an opportunity to increase the market access to Galleri immediately in the short term. These are also scalable. Also, your digital health partnerships are driving health system engagement.
As we work with the digital health partners on their post-positive follow-up for cancer signals that they detect, as those are referred to health systems, either that are already partnering with GRAIL and have already incorporated Galleri, or if those health systems haven't, that's a catalyst for those health systems to engage with us so that we can integrate Galleri into those health systems going forward.
It also gives us an opportunity in terms of international expansion, as many of these digital health partners, even though they're U.S.-based, have global operations. That's also an opportunity for us to expand Galleri with these digital health partners ex-US. We're also growing in the self-insured employer space. We have now over 150 self-insured employers that have incorporated the Galleri test across multiple different industries.
The key driver for many of these self-insured employers is that cancer is the top condition now for four years in a row, driving increases in costs for employers for their health plans. There is a big focus for the employers to get those costs down. We are working with 14 national and regional payers now that are supporting these employers. Those 14 national and regional payers are processing claims, giving them access to Galleri data for their beneficiaries, which is helping us engage with those national and regional payers going forward.
This ecosystem also means that health systems get involved for positive Galleri tests, again, driving this ecosystem, connecting employers, health systems, and payers. In terms of these health system partnerships, we have the Mayo Clinic and Dana-Farber publications, which are real-world evidence, which have shown performance in the real world has actually exceeded our clinical trial data.
With, you saw earlier, PPVs in excess of 70% published by both Mayo Clinic and Dana-Farber. We have multiple additional health systems who have partnered with us, who are working on their own publications of their own real-world evidence. We have a number of health systems that have incorporated Galleri into their primary care and specialist workflows, such as Rush, Community, and Mercy.
Many health systems have taken the next step and incorporated it into their own employee populations. Intermountain, HCA, Community, and Children's Health now offer the Galleri test to their own employees of the health system. Again, this is driving more payer engagement as health systems come on board. With that, enough hearing from me. I think it's now time to hear from our customers.
If we can bring up Anil Saldana, he's led the integration at Rush in Chicago, where they this year integrated Galleri into their primary care and specialist organizations. Dr. Andrea Klemes, Chief Medical Officer of MDVIP, is going to join us. They were one of the first, if not the first, partners for GRAIL back in 2021. They've done tens of thousands of Galleri tests throughout their network.
Dr. James Friedman, internal medicine physician from Scottsdale, Arizona, incorporated Galleri in 2021, done, I think, over 2,000 tests in Scottsdale for his patients. And Dr. Eric Sue, I think, incorporated Galleri in 2022 and now done over 1,000 tests in his practice in Century City in Los Angeles. Please come up, and Josh is going to moderate a panel.
Okay, we're back on. Please. And do we have Dr. Klemes on the video?
I'm here.
Hi, Andrea. Thank you so much for joining us.
Thank you.
Can you hear us okay?
Yep, all good.
Oh, there she is. Great. All right. It's a pleasure to have you. I guess we've done introductions, so we might as well jump right into it. Before we do that, is there anything you'd like to say about your backgrounds? Anything else, Eric, Anil, Dr. Friedman? Nope? Okay. Let's jump right into it. Let's start kind of big picture. Let's talk about what drove each of you in your own ways to adopt multi-cancer early detection testing and how you do that within your practice or your organization. Eric, maybe we'll start with you.
Sure. I only became aware of GRAIL and Galleri cancer screening in September of 2022, a little over three years ago. I only became aware of it because one of my patients asked me about it and had never heard about it before. We reached out to GRAIL, and they presented us a lot of the information that you're hearing today. It sounds really incredible. My first thought was, is this going to be the next Theranos where it's a lot of smoke, but is the technology actually there? Here I am three years later, 1,034 Galleri screenings with six true positive Galleri tests. I think it's incredible stuff, and I think it's only going to get better.
Eric, maybe just to follow up, how do you communicate the value of early detection to your patients?
We all know the toll that cancer can take not only on patients, but on families and loved ones. If heart disease and cancer are the top two killers in the country, and most of our patients are hopefully not dying from cardiovascular disease because we're proactive from that standpoint, how can we be more proactive from a cancer screening standpoint?
With the five current cancer screening guidelines that we have available, we're not really doing that great in terms of being able to detect cancers that people are dying from. By offering Galleri cancer screening, all we're doing is offering ourselves an opportunity to take a huge step from a proactive screening standpoint when we know that early detection matters.
That's great. Thank you. Anil, tell me a little bit about what led Rush and your push at the Rush health system to include Galleri, and how does it kind of align with what Rush is trying to do as a leader in healthcare?
I just want to take a historical break in terms of what Rush is. Rush kind of started with the medical college, and it was incorporated in 1837, a few days before the city of Chicago was incorporated, basically. We are pretty old, like 170 years plus. Rush was named after Dr. Benjamin Rush, if you remember, who signed the Declaration of Independence.
We have a long history of being in Chicago, a major city, and catering to our communities. Rush is focused on a mission, which is around something called Chicago's death gap. It is very interesting. Depending on where you are born and work, so if you are in what we call the Magnificent Mile in Chicago downtown, and you take four subway stops west, you live 16 years less.
An interesting age discrepancy that our researchers found a few years ago, and we have called this the Chicago death gap. If you go south, it's 30 years and beyond. Chicago has a life expectancy issue. When we looked at some of the contributing factors, cancer was one of them. Fast forward in different directions. I work for a health system. That's really complicated just for me to say health system.
We are three major hospitals, multiple outpatient centers. When you have a complicated system, there's a lot of problems, right? One of our mandates is to improve cancer screening as part of our quality efforts. If you look at the challenges that you see in cancer screening, you will appreciate a test like GRAIL, right?
The screening we do really well, not just Rush, but as an industry, we do really well on breast cancer screening. Lung cancer, we suck. Absolutely suck. We only looked at five cancer types for which you have designated screening or diagnostic tests. When GRAIL was basically talking to Rush in the early days, of course, I had a history with GRAIL. I was on the founding leadership team of a company called Tempus 10 years ago.
I used to talk to researchers from abroad who used to tell me, "There's this new fascinating area called liquid biopsy." I was like, "Wow, this is going to revolutionize cancer detection." This was 10 years ago. When GRAIL started talking to us, our Director of IRIS screening, Dr. Lisa Stempel at Rush, she's screening patients, leading programs, this mammography advance and stuff.
We really find it very, very hard to screen patients. Of course, there's quality numbers to meet, but it's not easy as a system to do this recommended screening. When you have all these challenges with screening, we looked at this test. It was very attractive.
There was one more reason, which our screening director, Dr. Stempel, she's an oncologist, she was very fascinated by the prospect of using GRAIL for aggressive cancers, for which there's no other biomarkers, no recommended tests. All of this put together, it was very attractive for us to embrace, not only to offer it to our patients, but also to look at this mission we have, which is to reduce the age discrepancy or Chicago's death gap. We did it for our mission, for our patients. Some of the other systems may have done it for other reasons, but for us, we want to offer the best outcomes for our patients, basically.
Thank you for that fascinating answer. Andrea, over to you. How do you think, or how has Galleri really fit into the preventive care model that you've implemented at MDVIP?
Sure. Thanks, Josh. Sorry I'm not with everybody today. I had a really bad travel thing over the weekend, and I decided to stay put this week. MDVIP, just a little bit of background also. We're not as old as Rush, but we have been around for 25 years. We're a national network of primary care physicians, like over 1,300 over the United States, taking care of about 400,000 patients. Patients pay a membership fee for an executive-style physical.
Unlike getting one at Cleveland Clinic or Mayo Clinic, you get a doctor all year long to work with you on your health span and action plan for wellness and prevention. Our mission is making healthier lives happen for doctors and patients. We like to take care of them both. We have 11 peer-reviewed studies showing that we identify more patients at cardiovascular risk, better control of chronic disease, more preventative care services done. We have less heart attacks and strokes, and our patients live longer if they're at risk. We save the healthcare system millions of dollars a year. You can see we've been focused for years on wellness, prevention, early detection, but mainly cardiovascular, diabetes, metabolic health.
My doctors would always ask me, "What can we do about cancer and brain health?" When GRAIL came to me before they launched, and my doctors, I know, like to be at the forefront of medicine, we did a pilot with them just to see how it would work in our network, if our doctors would enjoy—I do not know if that is the right word—enjoy using it. We had relationships with cancer genetic testing companies. There was not a lot of uptake with that. Once we finished our GRAIL pilot, we rolled it out. Over the last few years, we have done 55,000 tests. Almost every one of my doctors has ordered at least one. This has been the greatest innovation I have ever seen uptake in in my network. It gives my physicians that extra piece to focus on cancer prevention and really identifying it early because that's what we're all about.
Thank you, Andrea. James, for you, maybe you can share a little bit about why you've been adopting Galleri, but also maybe starting another thread about what you found as the most compelling and relevant performance metric that made you kind of want to adopt this technology.
My background is a busy practicing internist in Scottsdale, Phoenix area, so very heavy hospital work for 30 years. I am one of the early adopters of CT coronary calcium score back in 1987. I probably ordered more than anybody else in the Phoenix Valley. That has changed the trajectory of how we have managed cardio- and cerebrovascular disease, and it has been proven to be a great way of risk stratifying.
It is just now standard after maybe 35 years. I'm an early adopter. The physicians need to obviously manage complex patients, but we need to diagnose patients early. It's just the earlier, the better. I read about this multicancer detection serologic test, and I knew it was going to be probably early when I adopted it, but I have followed it. Really, going back to my days in molecular biology studying at UCLA, I knew that the answers are going to be in the DNA. I started using this test in 2021, and it has made a huge difference. One thing that's not emphasized, but I sat on our tumor board for 30 years on our campus at our hospital. I'm part of the Honor Health system.
At any stage that we diagnose cancer earlier than the later stage, we make a difference. The interventions, the targeted therapies that we have today, the pathway inhibitors, our cancer patients are doing so much better. I do not think that is baked into the data here. In a real world where I see and deal with patients, these patients who are diagnosed in stage two rather than three or stage three rather than four, I do see the outcomes. It is far better than just patients showing up with symptoms. If we can catch these patients early, it makes the difference. It has worked out great in my office. I have a discussion on top of all the other cancer screenings that I will emphasize.
It would be a disservice to patients to focus on this Galleri test without them understanding that this is an addition to everything else that they need to screen for. It's really important because year after year, they go, "Well, I had it last year." I go, "This is not a genomic test of your DNA looking for mutations. This is looking for circulating cancers." Now the patients understand that. Most of my patients want it year after year, and the uptake has been excellent. I'm very excited about the data. The data just proves what we're seeing, but obviously anecdotal to my patients. Now we get to see supportive data that just makes it even more exciting.
Was there any particular area of performance, like the false positive rate or the false negative rate or the PPV, that was most impactful to you?
I think all of that. The PPV is excellent, getting better. I also know that through machine learning and through the AI that's still evolving, it's just going to get better. Like all the DNA tests, we know this is going to get better. We know it. And so I'm very excited for the future.
That's great. Thank you so much. All right. We can see that across very different healthcare settings, different healthcare systems, there's this belief in the power of early detection and how it can translate directly into improved outcomes for patients. Let's talk about what implementation really looks like on the ground. Anil, how did Rush actually operationalize this, or how did they go about doing it? Then we'll get to everybody on the panel.
Yeah. I think I did mention I work for a health system, right? I want to say it again. I work for a health system, right? I mean, until you work in a health system, you do not really appreciate the complexity of healthcare. We started talking to GRAIL about a couple of years ago. Just going through the, I would say, the legal regulatory side of the house, it took some time.
We also, I think when we look back, it was a great decision from Rush where we required GRAIL to integrate into our EMR, Epic. That took some time. There are, of course, challenges with integrating with a major EMR such as Epic. When I look back, that was a great decision or a requirement from Rush mandating that we want this, right? We wanted our primary care physicians to offer this to our patients, right? It took some time. There were integration challenges.
Aaron mentioned about some of the changes GRAIL had to do last year. It was difficult from an integration perspective. That was just more on the ordering side of things. Inside Rush, we had to change a lot of things. We had to update our standard operating procedures, SOPs, the clinical workflows, train our employees, basically clinical staff. It took a long time.
Of course, you have to get people excited about a screening test, right? I mean, not everyone's focused on cancer. Here, we were just primarily focused on the primary care side of the house, not even cancer, at the system level. Just to give you insights into the complexity, we today offer GRAIL at four sites or four centers in the Chicagoland area, three major hospitals, but also a brand new cancer center that we built.
I think it was $70 million last year. It's a brand new standalone because for Rush, access to care is one of our primary strategies. When you say access to care, it means health systems start building new buildings, new hospitals all over the place. We offer GRAIL at four places.
We had the Epic integration, which allowed us to order. We also had to put together a clinical team, including a nurse practitioner, a phlebotomist across all sites who are available whenever we offer these tests to patients. I want to say this is a work in progress. We started offering GRAIL, I think, in September, right around maybe a week after that. We had a feature in Chicago Tribune highlighting Rush's choice of GRAIL. This blew up the entire region. We have not seen the kind of interest among our patients, among our executives, the family members of executives. It makes me look really good.
Thank you for that. Eric, maybe over to you. As you've introduced Galleri to patients, two things. One, what kind of language is resonating best with the patients about this? You have actually, secondly, managed to have a very high retesting rate, annual retesting rate. You've achieved upwards of 70%. What do you think's driving that level of patient engagement?
For me, I think it's primarily about starting a conversation. I will have a conversation with a healthy 25-year-old. I'll preface it by saying, "I'm going to present some information to you, not because I think you need it or even because I think you need to consider it, but just because I think it's something people should be aware of. Might this be something that you would want your parents to consider?"
You ask, "Have you heard about Galleri cancer screening?" and usually the answer is no. It's a newer blood test that's looking for tiny DNA changes when normal cell tissue becomes cancerous cell tissue, and it can screen for 50 different kinds of cancer. It's being described as a liquid biopsy, as a snapshot in time, where if it's negative, you've got a 99% certainty of not having any of those 50 different kinds of cancer at that moment in time.
There's no predictive value for a negative test, but it's technically being recommended to consider for anyone over the age of 50 because that's when everyone's risk of cancer increases, particularly if you have your own family history of kinds of cancer. Consider doing it on an annual basis, not as a replacement for any current cancer screening guidelines like annual mammograms for females starting at age 40 or periodic colonoscopies starting at age 45. It's meant to be as an adjunct to try to give ourselves the best chance at identifying any one of these cancers, most of which we don't have any ways to screen for. We mentioned that the overall risk of a false positive Galleri test is 0.5%, which is unheard of in the cancer screening world.
If you did get a positive Galleri test, the positive predictive value historically based on PATHFINDER 1 and actually meaning you have cancer was 43.1%. Oftentimes, people will hear that and say, "Well, so I do this test, I get a positive test, and I have a less than one in two chance of actually having cancer. That's not great. Do I really want to do this test and subject myself to that potential and going down that rabbit hole and not being found to have cancer?" What's the positive predictive value of an abnormal mammogram in actually meaning someone has breast cancer? 4.4%. What's the positive predictive value of a positive Cologuard stool test in actually meaning someone has colon cancer? 3.7%.
one percent positive predictive value of a positive Galleri test in actually meaning you have cancer is an order of magnitude better than what we're doing as standard of care. Based on this PATHFINDER II trial data from just released a few weeks ago, now that positive predictive value has improved to 61.6%. Fascinating stuff. When you present that information, it's really compelling. Then you'll oftentimes get the question of, "Okay, if I do this test, do I need to do it every year? Can I do it every other year?
Can I do it every two years?" My response is, "If you find merit in this enough to start doing it and you get that negative test with that 99% certainty of not having any of those 50 different kinds of cancer at that moment in time, there is some data to support GRAIL's recommendation to do it on an annual basis." There is an American Cancer Society study from several years ago, completely separate from GRAIL. They looked at 300,000 patients who are at relatively low risk of cancer, ages 30 to 65, mostly female, nonsmokers. They drew a whole bunch of their blood, and they banked it. They monitored them over the course of three years for any incident development of cancers.
When GRAIL became aware of this study, they asked to access some of that banked blood for the people that were diagnosed with cancer. What they found was that Galleri cancer signal might have been detectable on average of 323 days before the cancer was diagnosed, essentially a year. There are some data to support their recommendation to do it on an annual basis.
If you think about starting to do it, getting that negative test with that 99% certainty of not having any of those 50 different kinds of cancer at that moment in time, and you get into a cadence of doing it every year, that if God forbid you as my patient are going to get cancer, we're presumably giving ourselves the best chance at identifying it as early as humanly possible so that it's as treatable as possible with the least amount of toxicity from a treatment standpoint. Why wouldn't I want that for my patients? Why wouldn't I want that for my family and loved ones? That's the conversation.
That's terrific. Thank you. Dr. Friedman, you've ordered over 2,000 Galleri tests since 2021. Love for you to share with the audience here what your workflow is like, and from the early education to how you follow up, and then also talk about patients who've initially tested negative and then how you have found cancer in annual testing.
I have a large practice. I'm coming from the zone of a busy primary care, basically. I'm internal medicine. I have a very busy practice. Lots of sick people, complicated illness, lots. I do about eight physicals a day, and I do a real physical. I mean, I am thorough. There's no shortcuts to doing the right thing and taking care of patients. I normally do address all their cancer screenings. It was a hassle. My office staff bucked a little bit in 2021. We have to have this kit.
The company has been great, just has made it so easy. My patients know about it. Some, they're highly educated people, so they often actually ask me about it, even if they're new patients, and I've never talked to them about it. It's just another 20 seconds of explaining. I usually tell them that we've done a great job with breast, colon, prostate. People aren't dying like they were.
75% of the deaths now are really from head and neck, lymphatic, gastric, esophageal, liver, gallbladder, pancreas, and other aggressive cancers. We're not doing anything for those cancers. I think the people understand that. If they can afford it, they do it. Eventually, this is going to be a test that's going to be a lot less costly. I know it will be. We're going to do it for everybody.
I think that's going to be sea-changing for the field of early detection. How about people who've had a negative test one year? What's been your experience with annual testing? Again, I would say I have probably over 50% of my patients are getting annual testing now. Have you found cancers in people who were initially negative? You know, I'm working up a lady now who had a positive endometrial signal.
I did a transvaginal ultrasound. They didn't see something, but maybe they did. She's now going to get her MRI, and I'll send her to one of my GYN oncologists. She's getting her MRI at Mayo, I think, maybe tomorrow. I'm working her up. I think we found it early because this was her third test. I think we probably found it early enough, hopefully.
That's great. Andrea, we've talked about how Galleri is able to flex in different systems. We can integrate with EHRs. We can be delivered in clinical practice settings. Keeping that focus on prevention, you and your team have done over 55,000 tests. What's the most striking thing that you've learned about early detection, about the real-world performance and patient outcomes by looking at this vast experience within MDVIP?
Yeah. I mean, it's been exciting to see my physicians adopt this technology. I think they have similar conversations as the physicians here have said. When you know about the false positive rates of other screening tests, you can have that really good conversation with patients. I know it's made a huge difference. I know of a doc in Alabama who screened a 55-year-old male with no symptoms and got stage one esophageal cancer.
Those stories penetrate my network to say that this really is something. I have one of the leaders in the network not only lectures my docs on Galleri, but also prospective MDVIP physicians. He'll always say, "We have four screening tests, and for everything else, we just cross our fingers and hope." This is much better than that.
I was excited when you showed me the PATHFINDER II data to say that my cohort of 55,000 tests has the same positive predictive value, the same false positive rates, everything as the bigger study so that my doctors are comfortable knowing that what's happened in clinical trials is really happening also in our real-world cohort.
That's great. I'll just share an anecdote with the audience here. There was a congressional hearing in D.C. about MCED legislation. One of the patients, Roger, who had diagnosed with an early pancreatic cancer, was on the stage in the hearing. He was getting grilled about the lower sensitivity than single cancer screening, the false negative rate. His response to the congressional panel was, "Current clinical care in this country has a 100% false negative rate for asymptomatic cancer.
So what are you talking about?" That is what he gave back to the panel. I think it was a fascinating way to present that data, that our ability to detect unscreened cancers before symptoms present in current healthcare today is effectively zero unless something is found incidentally. I thought that was fascinating. Time to just wrap up. These stories and these lessons from you all are so valuable. But just in the last few minutes, in one line for each of you, in your mind, and maybe start with Eric, what's next for Galleri in your practice?
Standard of care. My hope is that something like this can become standard of care. One piece of information that I share with patients that I think is quite compelling is that there are now over 10 life insurance companies that are offering Galleri cancer screening for free to their clients because they see the data and they understand it's in their best interest to keep their clients alive as long as possible. It's an interesting dichotomy between the end game of a health insurance company and the end game of a life insurance company. Absolutely, I think my hope is that something like this can become standard of care.
Rush, what's next?
The keyword I wanted to mention with our strategy with GRAIL is we have systemized the Galleri test. That's a very important keyword. We are the only system in the region to offer the systemized workflows for Galleri, which means we not only offer follow-ups to the patients we screen at Rush, but for everybody in the region with the positive signal. We are already seeing those patients from concierge practices, from rival systems who have not systemized.
We are getting those patients into Rush for follow-up care, like diagnostics, whatever. That is why we took a long time in systemizing the Galleri test. This is part of our system strategy going forward already.
Thank you. James, what's next for you?
I would just echo what Eric said. I really think that this, I've been in practice 39 years, and I have not, I think, led my patients astray ever. We have enough evidence, I have enough evidence, that I know this is going to be standard of care in the next few years. I will continue to be using this test in the future, of course.
Thank you, James. Andrea, let's close with you. What do you see as the next step for Galleri in your organization?
Thanks, Joshua. Yeah. We're looking at the differences in adoption across my network because we do have 55,000 tests, but that's out of 425,000 patients. We know we need more adoption across the network. How can we increase utilization?
We've done some fun things like events in the doctor's offices where you guys are so nice and bring in a phlebotomist, and we do the test on all the patients who show up at the event. What other things can we do like that? What other ways can we make GRAIL available to our patients so that my doctors can say the same thing that the gentlemen on the stage can say, that this is the standard of care?
Thank you so much. Just in closing, I want to thank our amazing panelists for your contributions. Obviously, this is the type of technology that can transform the way you deliver care to your patients. It gives you a new tool to address the burden of cancer in ways that we've not had before.
I want to thank you for your efforts, for the insights that you've shared with us today. This is just the beginning. Hopefully, we'll all come back in a couple of years and share even more. Thank you very much. What's next? Yes, Andy, come on up. We're going to do a Q&A now to the team. Yeah, Andy, you were going to join us up here for Q&A. I'm sure there are some great questions. Andrea's still on the line as well. Where do you want to start? Any questions from the audience? Doug.
Two quick ones. Dr. Saldana, and first off, thanks to all of you for taking the time to do this with us today, to all of you. My guess, and I could be wrong, is that Rush has a much more diverse mix of patients than the other panelists when it comes to reimbursement profile and economic status. Again, just correct me if I'm wrong. If that is the case, and given, at least in my experience talking to physicians, there tends to be a bit of concern about accessibility and making certain tests available to some patients and not others based on insurance or economic status. How do you manage that?
Great question. When we started offering this test, it was a serious consideration. In our case, we are offering this test to the patients. We have a three-tiered approach. Anybody above the age of 50, we send out emails, and we tell them, "Hey, this test is available." In the EMR, anybody above the age of 22 with certain conditions, like smoking history, cancer history, like first level of relationship, and so certain conditions, anybody above the age of 22. The third tier, what we call, is anybody who wants it.
These are all the patients we offer Galleri tests. We are highlighting that, look, this is not FDA approved, and it's not covered by commercial insurance, and it's out of pocket. Also, if you look on the Rush website where we talk about the test, there is FAQ. We have a section which you can review which says, "Is this covered by insurance?" There are certain, I would say, like Tricare, I think they're covered for certain conditions.
That is the extent to which we have gone in terms of reimbursement. Like I said, we have a diverse population with disparities. We are looking at philanthropy and other, we are also talking to GRAIL to see how we can offer these tests. Again, do not quote me as this, like the word, but this is something we are looking at offering to our diverse populations. We only started offering about two months ago, and already the demand is so much just from the patient side. For the diverse, we are looking at innovative solutions through philanthropy and others. Yeah.
Thank you for that. And then just very quick, this can be kind of yes/no. The way the company and I think, Josh, you talked about Galleri. I mean, this is truly supposed to be a complement to other tests for screening that are in guidelines. It doesn't sound like you have had any concerns or anything in your practices that would suggest a patient getting a negative Galleri test that emboldens them to not use other tests that are in guidelines. Is that the case?
It's my concern. I think education, that's why you have to talk to the patient. I worry that the word will be out that this is just the holy grail and that I don't need to do anything else. Quite the opposite. Every patient needs to know that this complements what we already do, and it has to be done annually. It is not a genetic map of your DNA that might give us clues that you have a risk.
If we do not educate the patients correctly, there are going to be patients who fail to seek out care when they have symptoms or will declare themselves cancer-free. This test has to always be done in conjunction with the screenings that are required.
I will just add one thing from our studies. That is a huge safety concern for us and for the FDA, by the way. We have been measuring in our studies, PATHFINDER and PATHFINDER 2, by survey, by patient self-report, are they more or less likely to continue with their standard of care screening. What we are finding is that when you are taking Galleri as a screening, you are actually more likely to continue with your current cancer screening because it emphasizes the importance of screening as long as the education is there correctly, that in no way is this ever a replacement. Yes.
Thank you, Josh. How important is the Galleri data more to you guys? Would you ever consider switching to other vendors given there are other MCED tests coming online?
Maybe start with Eric.
The data is super important in having that information to present to patients and to stand by. I oftentimes will talk about the comparison with Guardant Health, which last year came out with Shield as a blood test looking for cell-free DNA that's specifically looking for colon cancer. If colon cancer is present, Shield has shown to be 83% sensitive at being able to detect it, which is not as good as Cologuard at 92%. Shield has also carried a 10% risk of a false positive. Shield was FDA-approved last year. Because it's FDA-approved, it's fully covered by Medicare.
You contrast that with the overall risk of a false positive Galleri test, again, of 0.5%. If something like colon cancer is present with Galleri, Galleri offers an 82% sensitivity at being able to detect colon cancer, which is very similar to what Shield is offering. The Guardant information, I think, is based on preliminary case-control data where they do not necessarily have interventional real-world trials that validate what they have seen preliminarily. I hope that answers your question that I do think that data is hugely important. I feel like GRAIL has been accumulating a massive amount of information over the course of the last four to five years. They are only going to accumulate more.
James?
Oh, sorry, Eric. Oh, go ahead.
Yeah, just to follow along on that, I mean, we get a cancer signal origin as well with Galleri. It reminds me of the patient who I was working up an anemia. The next month I saw him, he didn't send in the stool cards. Finally, the following month, he did. I called him to tell him they were normal. He told me he would let his dog know. He wasn't about to do it from his own toilet.
He went out to the front lawn and took a sample of his dog's poop. What I'm trying to say is the patients come in every way, and they don't understand the importance of why we're working anything up. Sometimes they want the least path of resistance. I think this Galleri test is after they've, it's an addition of the screening. I keep emphasizing that. This test is far better than Cologuard. How many patients did I call with positive?
These Cologuards were done because they did not want to have endoscopy, and they were low-risk people. Basically, 95% of those phone calls ended up with an endoscopy, and we did not find cancer. This is a far better test. How about compared to the other MCED tests that are out there? Again, the CancerGuard has no cell site of origin. I do not think it has the data. I am not going to use it.
Josh, do you want to comment about that?
Please, Nima.
Just as an anecdote, I mean, the CSO, I think, is incredibly important for my comfort level of ordering this test and feeling confident with the workup. An example is last week, I was in our liver tumor board. Hepatocellular cancers are usually not worked up with a PET CT. This patient was worked up on the outside.
Somebody ordered a PET CT. We reviewed it. They had a very large hepatocellular carcinoma that had absolutely no FDG avidity within the tumor. It was completely unapparent on the PET CT. If you got a contrast-enhanced multiphase CT scan, it was right there in your face. That concerned me because I think other tests, when they do not provide a CSO, recommend a PET CT, and you could just be flying completely blind. There is no impetus for somebody to be like, "Maybe let's order a CT multiphase of the liver to look for a liver cancer." You really would not do that.
I will also just make one other comment. We have looked because we get asked this question all the time. There are no data available today worldwide supporting the use of whole-body imaging for cancer screening. The only studies that have ever been done are outside the U.S. The conclusions of those small studies were that it is not appropriate for early cancer screening. Again, I think I would recommend there are lots of approaches to multicancer early detection. Some have CSO capabilities. Others do not.
I think I'd ask for the data to support the use of their whatever approach may be, whether it's ours with the CSO or theirs with whole-body imaging. There are other tests, again, that just are relying on case control data. Everybody needs to know the questions to ask. When you get presented with that, you need to ask them, "Is this really do you have any interventional data to support this?" Too often, we've seen case-controlled data. I guess the best example is the Thrive study, the DETECT-A study.
Bert Vogelstein, one of the world's leading oncologists, did a case-controlled study that showed amazing results. It was put into healthy 65-year-old women. The blood test barely worked. The PPV was 5.9%. They had to do whole-body PET CTs to find any cancers. Again, ask the right questions. I think it's really important. Andrea, how about for you? How do you feel about the importance of data?
Importance of data, sorry. Yeah. We recently had this discussion, you and I. As the Chief Medical Officer of a bigger company, I have all the companies coming after me to talk to me and try and pitch their wares, if I want to say it that way. I am sitting through listening to data, looking at how do we analyze it. I lean on external advisors to say, "What's the right type of data?" For now, we're still working with GRAIL for continuing above our 55,000 tests because you have the most data and interventional, not case-controlled.
All right. Thank you, Andrea. Other questions?
Hi.
Yes, sir.
How do you think demand for GRAIL tests will change if it gets FDA approved? Do you expect Medicare to cover it? How many other payers will cover it too?
Maybe start with Andy and then ask the panelists.
Yeah. As you know, we're working with Congress to get MCID legislation passed into law. Medicare cannot pay for screening unless there's an act of Congress. That's what we're working on right now. Josh can share more about the status of that legislation.
It is our anticipation that our longer-term reimbursement plan will include Medicare once that act of Congress is passed. We will be able to offer all Medicare patients at some point in the future the Galleri test. We're also working with other payers right now. We're early on in our payer engagement. The NHS-Galleri study results are going to be a key component of our payer engagement. PATHFINDER II is also a key component.
Obviously, FDA approval as well. As we know from payers, the clinical data, having the clinical data published and having an FDA approval will dramatically increase their willingness to provide coverage for Galleri. That is our long-term plan to ensure that patients get access to the Galleri tests.
If any of our panelists want to jump in, how do you feel that an FDA approval will change the demand that you're seeing from your patients? Do you think it will measurably affect that, or will reimbursement itself be the biggest issue?
I want to say from a Rush perspective, we'll remove the disclaimer. We have it at every place. That's the only big change we're going to do because we're already seeing the patient demand, basically. Just as an example, to keep up with the demand for screening at Rush, we are holding, I think, GRAIL camps at our four sites in December.
We only started two months ago, and we already have really big demand for screening. From our side, we're going to remove the disclaimer. I think it's just better for patients to get covered either through commercial or Medicare or any of these. From a system perspective, I think more, I would say, patients and the community members will have access to screening.
I'll just remind you something Andy said in his talk. Self-insured employers are effectively payers. They are reimbursing the test for their employed population. There is, in that regard, reimbursement already.
The second question is just from your real-life experience. Do you do the second test if you get a positive test? Doing two tests, how much do you lower the false positive rate?
We do a second test if the first is positive and we've done a workup and we have not found a cancer. We either will do more of a workup, then we'll repeat the test. I like to repeat it at three months. And if it's positive, then it's likely there is a malignancy. If it's negative, then it's unlikely that there is a malignancy after we've done a good workup.
Right. When you get a positive test the first time, how often do you get a second test that's positive?
We don't because we've worked the patient up, and we've found a malignancy. Then we're not going to do the test again.
I think you're asking if, let me see if we've got your question right. You get a positive Galleri test. They do a workup, right? Are you saying the second test being like the imaging test?
No, I'm sorry.
Or another Galleri test?
I thought a lot of doctors would if you just give a straight blood test and it comes back positive, you just follow up with a right to a blood test.
No. No, no, no. That's not at all what happens. Yeah, let's clarify that. So a positive blood test gets followed up by a directed workup. So Galleri will say cancer signal detected, predicted origin liver. The next test is not another blood test. It's an image of the liver, hopefully not a PET CT, but the appropriate type of imaging test of the liver to find the cancer. If nothing is seen and the doctor's convinced it's been an effective workup, then you would do another Galleri test to try to reach resolution.
And if it's negative, you can pretty confidently assume that that first test was a false positive. I don't have a number for you that you're looking for about how it lowers the false positive rate just because we haven't done that in a large enough population yet.
If I can chime in.
Oh, please, go ahead, Eric.
To help answer that question. I think GRAIL has some data on retests. Following an initial positive test, you take that diagnostic evaluation. You don't find cancer. GRAIL offers a free retest at whatever time interval. I think the data that GRAIL has is involving 145 patients that were retested. 30% of them, again, tested positive and were persistently positive and then reevaluated for cancer and perhaps, in fact, identified to have cancer. The other 70% had a negative test that was repeat. They were followed for 18 months and not identified to have cancer.
I think that's where they're getting the information to say that if you repeat a test and it's negative, you can be fairly certain that that first positive test was, in fact, a false positive and that you just resume your annual Galleri cancer screening as you ordinarily would.
That's right. There was only one example I'm aware of where a blood test was done twice in a row. That was in the Thrive study, and that was, again, because the blood test wasn't working. I think there's a question. I just have a really quick one, and I guess it's for both the physicians and GRAIL.
Just can you remind us if it's done on a fasting basis? And if it's not, do you get some interference? That could contribute to some of the false positives that you see and need to tell the patient maybe, "Did you, in fact, fast?"
Just a quick one, hopefully. My understanding is that it does not require a patient that needs to be fasting. Oftentimes, when we have patients come in for their physicals, they are fasting anyways. We introduce Galleri cancer screening by starting the conversation.
If it was something they wanted to start doing, then maybe doing it at the time of their annual physical would make a lot of sense because each time that they come in for their physical, they would be able to repeat the Galleri cancer screening. To my knowledge, I do not think that if you have eaten, that it is going to affect the Galleri test result in any way.
We offset the test by six months after they've been in for a thorough physical. We've done comprehensive blood work. They come in every year for physical. They come in every year for Galleri. The Galleri is six months from their last physical. We've done that on many of our patients. We think there probably is some theoretical advantage to that.
There's no data we're aware of that suggests that food introduction has any effect on methylation patterns. There are hypothetical things like blunt trauma, other things that have happened could affect your methylation, being on a methylating chemotherapy agent, for example, which is why we don't do Galleri in people who are actively being treated for cancer. Nothing we're aware of as it relates to food. Okay.
If there are no other questions, I think that will wrap up our program today, if I'm not mistaken. Alexis, am I correct? Yes, correct. All right. I want to thank our panelists. First of all, thank you so much. I want to thank our esteemed audience, everybody who made it here despite the difficult travel schedules and the uncertainty. It's highly appreciated.
I want to thank Dr. Klemes for continuing to hang in there by video. It was terrific having you to be part of this. Again, I want to thank everybody for being here and the staff at GRAIL. Hopefully, you'll be getting tours or have done tours. I want to thank all the GRAILers for all their hospitality. Thanks, everyone. And the other speakers. Thank you.