Thank you, everybody, for joining me today. I'm David Westenberg, the Life Science, Tools and Diagnostics Analyst here at Piper. With me is Aaron Freidin, the Chief Financial Officer of GRAIL. We'll just start it off with the guide, 40%-50% growth for Galleri. And, you know, I believe you said on the last call, 2025 might be below the growth levels of 2024. Can you walk us through, you know, kind of a little additional color into that, brief 2025 commentary?
Yeah, David, thanks for having us. So we're, you know, we've been on the market since April 2021. We've done over 250,000 tests. We spent a lot of time experimenting in what works, how to sell, how to implement a first-of-its-kind multi-cancer test. You know, now we're focused on really extending our runway and making that a capital-efficient growth mechanism, not so much an investment. So we've, last quarter, we announced we did a restructuring with that. We will be not expecting to grow as fast in the U.S. We will still grow. We will guide what we expect to grow at, at year-end when we release those results, but it'll be below the, you know, 30%-50% range that we gave.
'Cause again, we're gonna really be focused on getting our U.S. commercial investment to be cost-neutral, basically, as we're building awareness and integrating the test into, you know, various, you know, scenarios or environments.
Yeah. And sorry to go directly at this, but I mean, it's the elephant. Like, the Illumina original acquisition thesis did have, you know, implied a lot more revenue than what we're seeing today. In terms of lesson learned and, you know, kind of what did not go as expected, you know, can you run us through some of those things that didn't go as expected and what those lessons learned are and then kind of where you're going from here, you know, with a boatload of knowledge that you've learned over the last, you know, three years?
Yeah. Yeah, so you know, one of the major complications that occurred, which was the antitrust cases that came in, we were never really allowed to integrate into Illumina, a lot of the thesis was that we would be able to take advantage of their global infrastructure, to seek regulatory approval faster, and just a broader adoption, globally, but since the companies were required to be held separate, we were never able to take advantage of that, it made for a much faster spinout given that nothing was integrated, but you know, one of the primary reasons for us not achieving that was the fact we couldn't leverage any of their infrastructure.
Gotcha. Okay. You know, you mentioned FDA approval and reimbursement maybe two years away. Can you talk about your plans to build the market before that time, and then, you know, how you do that in a cost-effective way before you gain reimbursement?
Yeah. It's a great question. It's really why we're in the market today. You know, again, selling the first-of-its-kind, paradigm-changing multi-cancer screen, wasn't something that we're just gonna, like, fall into with broad reimbursement and be successful. We're out in the space now. You know, we're working with physicians, you know, working on the test report, nice and simple test report for physicians and patients to understand, understanding how health systems are integrating the test into their protocols, into their workflows. There are some health systems out there that have developed early cancer detection, multi-cancer early detection, clinics, where they're figuring out then how to take that positive and make sure that person gets worked up, that there ends up being a diagnosis or a resolution.
That's really enabled us to get really good experience on how to do this when we have broad access, so we're not talking about 5-10 years of figuring it out then. We can hopefully ramp faster and integrate more quickly, but it's the primary reason why we're on the market today.
Can you just maybe give us an update on your progress towards reimbursement? What are the upcoming milestones? What's the outlook overall? You know, what's a good thing to track in terms of us as investors as we wait for that? And then in terms of strategy around legislation, I mean, could some of these biomarker bills help get coverage?
All right. We'll start with the regulatory where we're at with the FDA. So we've been in a breakthrough designation for quite some time now. We knew this would be the first-of-its-kind test that the FDA would be looking at, and we're in regular discussion with them. So, you know, what we've got coming up is our the remainder of our module submission that we're in, with the final modules being the Pathfinder 2 data and the NHS-Galleri data. That's a total of 175,000 participants in those studies. It'll be submitted to the FDA as the final module in the first half of 2026. We then would expect there to be about a year review time from there, including an AdCom.
You know, if you think about it, like, we've had to spend a lot of time getting them and to understand, like, single cancer assessments and screening is different than multi-cancer. So you know, again, it's why we engage so early with them. We believe we're in a good position here to submit an approvable package in the first half of 2026. As far as inside legislation goes, as we all know, there's you know, two ways to get reimbursement through Medicare, and then, you know, broader, more commercially, the USPSTF. Then there's the legislation path that companies have taken previously. We're really proud of, you know, the large coalition of advocates who've put together and progressed the legislation to date.
It's got bipartisan, bicameral support to cover, to allow CMS to cover multi-cancer early detection tests. It's well-positioned, and you know, I, I can't sit here and predict when legislation will, you know, be voted upon or what's gonna happen. For us, ideally, that legislation would pass prior to FDA approval. So we've, we've got a couple of years before that has to be done.
Got it.
As far as the biomarker bills go, I think not really screening relevant.
Mm-hmm.
Current read and understanding, more precision oncology.
Perfect. Interesting. Can you talk about the important steps in the FDA regulatory pathway? Kind of what, what conversations have you had with the FDA and, and what, what do you think they wanna see from you? If you wanna, you know, give a little, I know you just gave color on that, but maybe a little more specifics on that.
Yeah. So it's, you know, as I mentioned, we've been working with them for a while. They've looked at our NHS Galleri study, the original Pathfinder study, the Pathfinder 2 study. Those have all been done as IDEs, and they've seen our test performance to date, so it's gonna be, in my view, the most important thing for them to see is performance continue. Like, our performance didn't degrade from our research studies into our interventional studies, and, you know, once the Pathfinder 2 study reads out and the NHS study reads out, that'll be 175,000 folks with, you know, performance data. The NHS Galleri study will also, since it's longitudinal, have a clinical utility aspect to it. You'll be able to see stage shift from the control group versus the Galleri group. Something that, you know, if they're interested in, we'll have.
But I mean, they've said they're gonna look at performance and safety in the U.S., and they wanna make sure that any MCED test has the ability to localize the cancer, and not everybody's just getting pushed to some sort of full-body scan, so we're encouraged by those facts.
Gotcha. So the tumor of origin is a changing factor for them.
Mm-hmm.
Okay. Can you remind us what your tumor of origin accuracy was last?
It's about 90%.
Okay. Great. Now, going back to dollar-efficient, you know, you have a commercial strategy where you want to keep this dollar-efficient. Now, PCPs, of course, are located all across the country, you know, most numerous doc. And, you know, how do you keep that strategy dollar-efficient just given the fact how much they are distributed?
Yeah. So, we've had several different commercial approaches to the PCPs since we've launched. So we've done the go everywhere, find all the Galleri tests, see what uptake is. And we've, you know, realized that that's not as efficient as just doubling down on concentrated areas where we're actually seeing more success. So that means we can use less reps, you know, scale-wise. Prior to the restructuring that we announced, we had about 400 folks in commercial with about 200 being quota-carrying. After restructuring, we've got about 200 folks in commercial with 150 being quota-carrying. So really focusing on the folks out there on the street, you know, for clinicians and then also our self-insured employers and so on.
Mm-hmm.
You know, making sure that we're able to, you know, drive efficiency there.
Gotcha. Sorry. This is not part of the original questions, but it's kinda interesting. So, I mean, what are these are these concentrated markets of ordering? I mean, is this, you know, higher economic areas? Is this populations with older people? I mean, what's kinda the key?
It can be a mix of things, and you know, some of those areas include both those things. So higher income is definitely helpful. It's a self-pay test. It's not reimbursed, but we're also finding that regions where there's a KOL or a physician that is a true champion, where you know, where there's a health system that has enabled their physicians to offer the test through self-pay, so there's kind of a brand-name health system in the area. You know, some of the, you know, probably more tactical things that we've learned is you need to run, like, statistically, about 100 tests to get a positive, but you can run 200 and not get a positive.
Physicians who run 100 or 200 and don't get one, they're probably not gonna order it as much as somebody who runs 100 or 50. So we're putting together these doctors with each other so they can hear from each other. You need to put together large numbers when you're chasing a 1% incidence, right, disease. And we're finding that real-world data is really helpful and impactful.
Gotcha. Now, I mean, you're constantly innovating. I mean, that's what you need to do as a company and spending money on R&D as well as other costs, so just can you talk about your plans to remain solvent long enough to achieve profitability? Can you remind us your cash flow runway and, you know, what are your needs in terms of raising additional capital before you become profitable?
Yeah. So at the end of Q3, we had $850 million-ish on the balance sheet. We guided we'd burn $220 million for the rest of the year, so that puts you at about $105 million for Q4. So we'll end the year somewhere around $700 million-ish. So we've got cash for some time. We see cash into 2028. In 2024, we've finished the last blood draws for the NHS Galleri study. We've finally finished the enrollment for the Pathfinder 2 study. Those are, again, that's 175,000 folks. Those costs, you know, are gonna subside. We will finish development of the next generation, next version of the test, which we'll launch this month, which is a lower-cost, high-throughput version. Those there'll be some cost continuing into 2025, but eventually that will stabilize and also provide a higher gross margin. And then we expect to continue to grow.
So we see, you know, runway into 2028. We've got to execute against our plan. There's some, you know, assumptions in there that costs, you know, commercial's gonna start paying for itself. But, you know, we've got enough time to make adjustments if we have to further that runway.
Got it. Lastly, maybe you can even talk about some of the differences, potential differences between the first and second-generation of Galleri tests. I mean, you mentioned speed and profitability. I mean, are we gonna see anything in terms of sensitivity, specificity? I mean, I think specificity's a little harder 'cause you're—I think you're at 99%. But, you know, any other kind of tweaks you make to the test?
Yeah, so performance-wise, it was designed to be non-inferior to the current version.
Mm-hmm.
So at least it'll be at least as good as the current version. It may be better. It'll be at least as good, and its specificity's at 99.5%. So no, no changes there. That study, that development was done to get to a high-throughput, lower-cost version to support a PMA, to support NHS adoption if the U.K. decided to roll it out. So what you'll see in 2025, once we, you know, roll it out at the end of this year, as volume switches from one version to the other, is there'll be a variable cost improvement, to begin with. You know, with regard to variable costs, we've really pushed down the cost of sequencing. We're putting four times more samples on a flow cell in this version than we were on the last version.
And then what you'll see over the longer tail, as we get more demand, as we receive more tests, is the fixed cost leverage. We built a highly automated, robotic lab, which will remove a lot of direct labor, but we'll have to grow into the scale that we'll have built there.
Gotcha. Okay. Just in terms of the degree in which you can cut costs or COGS with the second generation of tests and, you know, what's the—is there an end goal to get to?
As low as possible. No. So, you know, we've guided the U.S., you know, gross margins, to 60% at scale. That's based off of this version that we're launching. It's gonna be, you know, have depended on the scale. As I've said, we've pushed sequencing costs down. We can focus on other consumables and reagents and then the wraparound costs, shipping, kitting, and all that stuff. But we've really optimized sequencing costs in this version. So, you know, with the scale, we will be able to get to what, where I mentioned.
Have you quantitated the gross margins from that? I mean, that is 60% overall. No upside from there. Then, what kinda operating margins would you expect to achieve in a 5-year timeframe?
Oh, five-year timeframe?
Yeah.
Yeah. So speaking of—in the U.S., you know, hard for me to predict out five years from now when we're gonna be going through broad reimbursement and scaling at that time period. I think long-term, we've guided operating margins in the, you know, 5%-10% range, as a business, in the next five years. You know, I think if you look internationally, there's opportunities to have better operating margins or increase operating margins sooner if we were to have an international health system or country roll it out. Just given that, you know, if the UK did something, there's no sales force really needed. It's a national health system. So your gross margins will be lower for sure. But your operating margins should be pretty healthy. So I don't have a ton I can guide you on right now, given how.
Perfect.
Interesting, the next five years can be.
No, no worries. Just in terms of, you know, don't even know what kinda word to use, but just this the entire Illumina saga, maybe just extremely dramatic. I used a different word in the question, but I don't wanna do that one thing. But something show. Can you just talk about, you know, how did that impact the company? And you know, how do you kinda get past that drama? Or you know, maybe it hasn't impacted you at all because maybe all the spotlight was on Illumina, but just to, if you can maybe just kinda discuss that, those events and how you kept, you know, the company together.
Yeah. So, loaded question. I'd say, you know, we have a resilient employee base that has just done an exceptional job. We, you know, we were acquired, announced in 2020, closed in 2021. In April 2021, we launched a test in the middle of COVID. And we've now done over 250,000 tests in that time period. You know, we were held separate the entire time from Illumina. We still were owned by them. We still had to report into them from a financial perspective, budgeting perspective. But we still got to have our own management team and so on. You know, I think it's been really good for our employees to be beyond this time period because it was just such a period of uncertainty. Are we gonna be more controlled? Are we gonna be less controlled? And so on.
But we were well set up to navigate that. And the other thing that we did that really helped was, you know, we put a small group of people in the day-to-day managing of, as you said, the drama and sheltered the rest of the company from it. You know, no matter what happened, if they executed, it would be better for everybody. So let's not distract folks. And we did a reasonably good job of setting that up.
Gotcha. And then maybe just walking into your biopharma business, you know, so where are some of the notable partnerships in there and what are some of the opportunities to grow that?
Yeah. So it's, you know, on top of Galleri, we've got this methylation. It's a methylation platform that enables Galleri and also our biopharma business partnerships. We've got a RUO assay that we're working with several biopharma partners on. The most notable is with AstraZeneca. They've just announced the use of our assay in a phase three lung cancer adjuvant study. You know, it's one of the first times a ctDNA test is being deployed in a phase three trial to target earlier cancers to see how well the compounds work there. So there's a business there that we're excited by. You know, AZ's the only one we've currently announced, but it's an area that we're continuing to work in, balancing that with making sure that we have all the capital we need to get MCED, you know, Galleri broadly accessible.
So I think there's more that we'll likely do with those assets, the MRD asset and then the diagnostic aid for cancer asset, as we think more strategically about how to monetize those assets.
Mm-hmm.
over 2025.
Gotcha. I mean, you are one of the unique with the using a more tumor-naive assay. I mean, obviously, there's Guardant, but there's not that many others. It's technologically difficult to do. It's sequencing intensive. I mean, is there, you know, maybe some sort of business development relationships or other kind of non-dilutive financing ways of getting that out to the market?
I'm sure there are. And those are things that we'll be looking at and considering.
Okay. ASP's been hovering around $800, I think, for a couple quarters here. Where do you see that going over time? And, you know, is this how, how do you improve that?
Yeah. So, you know, ASP's at $800 for a, you know, non-reimbursed test, essentially self-pay. You know, it's, we're pretty happy with that. I think, you know, long-term as this gets to broadly accessible. We see the price coming down, which is why we're focused on driving down the cost of the test. You know, at a population level, $800 to a test, for any sort of government or payer to payer is a good chunk. So we think long-term that that price will come down. Right now, it's a mix of the self-pay through clinics. We've got some self-insured employers who are buying the test as a benefit for their employees. And then we have, you know, life insurance partners, companies who give this test to their insured policies where their customer, the policyholder, whose incentives are completely aligned with theirs. Everybody wants to outlive the policy.
And the life insurance companies have seen that this really helps them achieve that.
Just in terms of getting to, you know, population scale, what has to happen operation-wise to get you into population scale size? And, you know, maybe we could just talk about all the different things that go into that vision, whether it be U.S. Preventive Services Task Force, legislation. I mean, anything that gets you into the, you know, true population test.
Yeah. So in the U.S., I think you've mentioned, you know, what it'll take. It's either legislation plus a, you know, CMS national coverage decision, or it's the USPSTF. Internationally, it'll be different. I think the NHS-Galleri study of 140,000 individuals is gonna, assuming the data is good, is going to open up doors for other single-payer systems, globally. We see interest today, you know, but we're really focused on getting that data out to hopefully make those discussions more rapid when they happen. And then operationally, you know, we're learning a lot commercially about how to implement, as I talked about earlier. But we're also running the back-end lab, right? We've built a lab capable of doing significantly more capacity than we currently have, significantly more tests than we currently have. We've got extensive capacity.
So making sure that that runs, it runs consistently. We've got the quality checks in place, you know, so on and so on. So regulatory, we've gone through what has to happen, to really enable that volume in the U.S.
We're out of questions. If there's any from the audience, let us know. I guess I'll just kinda keep going 'cause we have about.
Yeah.
Three minutes left. Maybe just if you could talk about sensitivity and understanding of sensitivity because, you know, there's a trade-off. You know, you could probably target three cancers and get an extremely high sensitivity rate, or you can get more cancers. So can you just talk about, you know, the, the trade-off that you've decided and, you know, you know, let people know how, you know, that, that 40%, 45%, something, sensitivity rate, you know?
Yeah. So I think at the highest level, GRAIL's finding, what the Galleri test finds is a methylation pattern from circulating tumor DNA in your blood. It's not looking for a specific tumor or a specific mutation or a specific cancer type. So it really comes down to the limit of detection of can you find it or not? Is that tumor shedding or not? So we're looking for cancer. We find cancers that we've trained on. We find cancers that we haven't trained on 'cause it's a common pattern that basically doesn't exist in people who are healthy, which is why you've got a 99.5% specificity. So that's the most important part. So to your question as far as, you know, picking three cancers, well, we're finding it's a signal that all the cancers show and find.
Could I change the denominator to only show three cancers? You could, but you're just basically masking the results of other cancers that you're finding. We think the right thing to do is return all results 'cause that's how you save the most lives on a population basis, and also the way the test performs today, stage two sensitivity is 70% for the you know 12 most deadly cancers, so at 99.5% specificity and 70% sensitivity, you're gonna save a lot of lives, stage two. Overall, I think the sensitivity across all cancers is 48.5%, if I remember right. You know, and that's higher for late stage, lower for early stage, for the early stage. You know, but not all cancers shed the same.
Mm-hmm.
Not all cancers are as aggressive as each other. So it really comes down to finding the cancers that you're gonna die from, not die with. And, you know, we believe that's what Galleri's doing.
Gotcha.
Oh, I'm sorry. I don't know if you heard me or not.
Yeah. But yeah, I'm just curious if you, if you've thought about that. Like, you know, we know you need to get pancreatic and ovarian and lung in those early. I don't know if you, if you've tried to focus a little bit more on that or if, if the focus is still trying to be broad.
Again, it goes back to what are we finding? We're finding a common cancer signal. That's not, we're not optimizing that to find pancreatic or lung or anything 'cause there's a common signal that all the cancers are sharing with the 12 cancers that kill, you know, 66% of people that I mentioned. That 70% sensitivity, that's kind of a version of that. We also, you know, you can look at metrics for unscreened cancers where the sensitivity today is zero. From a development perspective or from a biopharma perspective, it's not being optimized for any specific cancer. Our studies have all been done around asymptomatic individuals. Some of them have increased risk factors, whether they might have smoked in the past.
But we haven't done anything specifically looking at, you know, you've got a BRCA mutation or, or any of those subpopulations. I know some health systems are using it in some of those populations. But we, we haven't done anything specifically there.
We actually didn't have time for that one, but it's very good.
Thank you.