Okay. Welcome, I'm Tycho Peterson from the Life Sciences Team. Pleasure, a pleasure to have the Guardant team with us. First question is strategic review. This came up a lot today with your stock moving. A lot of speculation questions. Maybe just give us some backstory on, you know, what that meant..
Yeah, there's. We've had a lot of questions about that.
Yeah.
This afternoon. There's nothing to read into it. I mean, this is basically the board overall looking at executive compensation over the last 12 months or so. One specific area was executive severance, and so there was just a change, actually, just to bring us all in line with where the market is. And so it's as simple as that. It was simple housekeeping. And yeah, nothing much more to read into that.
Okay. No, no M&A?
No.
Okay. Let's jump into maybe starting with the Adcom. Obviously, you know, a good outcome. Maybe just talk a little bit about, you know, your view, post mortem there, and then a lot of questions for us on labeling. That was probably the number one question we got yesterday as we were out talking to folks, you know, various scenarios, first line, second line, or front line, second line, and with restrictive label, you know, unrestricted. So maybe just talk a little bit about how you think about the various paths forward on the label too.
Yeah, sure. So thanks, Tycho, for actually having us in this conference, and, I'm excited to have this conversation. Still, we are running actually very excited about what happened a couple weeks ago in our Adcom. I was very proud of our team in terms of the hard work, preparation, and the execution on that day, and definitely the final results was very pleasing for us. We, at the end, the voting was related to our proposed indication of use, which we went after getting a primary non-invasive CRC screening test, similar to other modalities, non-invasive modalities. And we were very pleased that at the end, the Adcom members actually gave a very strong, positive, recommendation. At the end, still, it would be FDA decision.
We are also pleased with some of the comments that FDA has made in that meeting, and the conversations are continuing with the agency. We are just 2 weeks after it. We continue to make positive, steady progress, and we see how it ends. But definitely, we are a lot more bullish about getting such label than couple days before Adcom, now that we are post-Adcom.
Does a 6-3 vote on efficacy, you know, versus maybe 9-0 change the labeling discussions going forward, or?
The way the process works is actually at the end, it's not. It's really a voting process. It's not just, you know, figuring out where the consensus is gonna get built. And even some of the best therapeutics, when they go to the panel, it's not that always they get unanimous support. We are very pleased with such a strong positive vote for the proposed indication.
Maybe a couple comments on AA. That's obviously been, you know, a big focus there. You know, talk a little bit about AA for Shield and, you know, how you think the feedback from the Adcom, you know, could influence conversations with the FDA there.
Yeah, I think in line with actually what we proposed to agency in terms of the indication of use and also the limitations of this device. At the end, our advanced adenoma sensitivity is 13%. This is what it is, right? So we propose to put a limitation that Shield has limited sensitivity in detecting advanced adenomas. And for people who have watched our Adcom, we are very crystal clear about it. We don't have any issue with it, and in fact, I think the conversation of the Adcom was in line with even what we proposed, that let's make sure it's transparent and clear that this test is good for CRC screening and has limited capability for advanced adenoma detection.
So I guess is the most likely, you know, scenario here, then first line with, you know, some restrictions around, you know, less than 2 cm and maybe asymptomatic patients?
So restriction in regulatory world is like, if label is gonna have something which would give restriction of access in terms of where doctors should prescribe the test, right? So I think some of this language of, okay, the performance of AA is this or not, is around limitations and precautions, and patients, doctor know that what you're getting is this, versus as a result of this AA performance, we are gonna restrict where you should order this test or on whom you should order this test. So that's what we expect to be in terms of at the end, the impact of AA. And when, again, we propose that first line claim label, indication, such a strong positive vote actually shows the support of the external panels, and I think FDA were leaning in that direction, too.
We are very pleased with that outcome.
If it ends up being second line, maybe talk about the viability, you know, of the test there and, you know, the path forward.
So when we look at actually CRC screening market, average risk screening, there are 120 million people eligible for screening. So a first-line label, effectively from regulatory and access and label, you can promote this test for all 120 million people. Second line means for the people who are declining other modalities or effectively unscreened patient population, that market opportunity is about 50 million people. Now, when you go to the reality of the market, colonoscopy is the prioritized option, so, the colonoscopies are not getting replaced at large extent with non-invasive option. In fact, that's, something that the, you know, doctors are even trying to avoid. So, as a result, the real commercial opportunity for first line is for 65 million people, as 55 million people these days are getting screened with colonoscopy.
That would be the range and the cap of what colonoscopy can do. We can do about 6 million annual screening tests with colonoscopy. We don't have even more capacity. So first line, 65 million today, second line, 50 million. There is some impact, but that would be the materiality of the label change for Shield.
Does the Epi proColon, you know, dynamic impact things here as the FDA kind of changed their view after that was effectively a debacle, right?
Yeah. So I think let's remember, Epi proColon study, the initial study did not meet the endpoint, and the Adcom voted down the approval of Epi proColon. One of the question got tied vote, and then the chair voted negative, so effectively it became a voted down conversation on that day. Shield is, for the first time, we have a very innovative blood test with performance in range with other stool-based test. Both primary endpoints of the study is met, very strong device, and Adcom vote was a strong positive vote. So I think there are some aspects of day and night difference of the sequence of event for Epi proColon and the reality of where we are with Shield.
How about interval? Can you maybe just talk, you know, how you're thinking about interval and any kind of discussions there with the agency?
So as you may have noticed in the Adcom, FDA mentioned that interval testing is something that we don't get into. That was, you know, not a surprise to us. They don't get into interval testing based on the amount of data that we have today. Typically, when you take these devices for PMA approval, you just have cross-sectional data at the first time point. In order to really take a stand on interval testing, you need to have performance when you're longitudinally monitoring the patient in programmatic testing, that nobody has. Those studies typically happens in a post-market setting, and, you know, takes many, many years to generate those kind of evidence. So that's probably gonna be a post-approval study that we are gonna do in line with what has been done before.
Really cost efficient, but pretty long kind of study that we have to do to confirm the interval testing would be appropriate as we are recommending it to be three years. Our recommendation have been impacted by the, what CMS think is medically necessary. CMS NCD is very clear. They went to open public comment period two years ago, and at the end, they put this, NCD in place that as long as you have some specific performances, they think this test should be used on a triennial basis. We are following the direction of, what they are setting, and as a result, our recommendation to provider is to use this test on triennial basis.
You've been, you know, done a nice job ring-fencing the spending, and you've been pretty clear about kind of your plan around reps, you know, 100 by the end of this year, and then scaling up to 300. I guess, what other proof points should we be thinking about between now and USPSTF?
Should I make a few points, and then I ask Mike to add some comments here. So, you know, we are capping our level of investment on Shield at the level that we think we are really adequately resourced to go after this big opportunity, but still really in a very financial, disciplined way. There are some milestones that we have to meet and beat in order to continue even that level of investment. For instance, having a positive Adcom was a milestone. Like, if the Adcom would not gone the way that went, we would have different kind of conversation right now in terms of operational adjustment. The next one, for instance, is FDA approval. Are we gonna get at the end FDA approval? We have strong conviction the answer would be positive, but that's a major milestone for us.
And as we go and we build, we further scale up this commercial team, we are gonna look at the revenue, the sample volumes based on our projections. Is this market that we always believe, and we have evidence it's a very deep market, one of the biggest opportunity ever in diagnostic industry. Was it real, or we were some kind of biased? If we figure out it's real, we are continuing to execute, we would continue that level of investment. If we figure out, no, the market opportunity for whatever reason is not right, we are gonna make significant material adjustment right after. So that would be the commitment that we have in terms of building this brand within the next few years. Do you want to add anything?
Yeah, I think, I mean, just to clarify that one, we spoke about ring-fencing $200 million a year, and that's $200 million net cash burn. So, you know, one thing that's gonna enable us to continue the investment on the commercial side is, you know, relatively quickly, this will have a positive gross margin. So as the revenues are ramping and we're generating additional gross profit, that's what we're gonna be able to reinvest back into the commercial infrastructure. So, again, as revenue grows, then it's gonna allow us to really push hard on the sales and marketing and drive that spend, but then that again that's gonna continue to drive the growth. So, yeah, but we're very focused on managing to a net burn of $200 million a year.
...You know, another question we've gotten is just the risk of the ADLT rate of $895 kind of being negotiated down over time. How do you think about that aspect?
So, yeah, I'm getting this question actually a lot. So 2018, as part of PAMA legislation, this ADLT got enacted into law. So let's remember actually why we have even ADLT process and status. Congress wanted to make sure that some level of innovations happen, some level of risk-taking happens by device manufacturers like us, lab developers like us, to go through significant amount of investments that we've done to build innovative, advanced diagnostic lab tests in exchange for some premier Medicare pricing after getting that ADLT status. So we've done throughout the years, all the investment, risk-taking, and now we are at the cusp of FDA approval and Medicare reimbursement, time to get benefit from the other side of the incentives that ADLT program enables for companies like us. The law is very straightforward.
For unmet need, as long as you get FDA approval, you're going to get ADLT status. We have ADLT status for Guardant360 CDx product for three years now, and we know... Right, three years?
Mm-hmm. Yes.
We know how the process really works. We know how the pricing is set. We know how you can defend pricing for a long period of time, and we are effectively executing on that strategy now for Shield IVD test.
The comment earlier on margins, I mean, I guess just thinking about that $200 COGS bogey you've kind of put out there, just talk about the path to actually get it down to that level.
Yeah, I think we see that again, relatively soon in 2025, you know, we'll have cost per test of $500. And then, you know, growing the volume is going to enable that cost per test to come down. We're very focused on the workflow, and we're investing a lot at the moment on automation, and we really want to take labor costs out of the lab. And so I think with the pathway that we have and the knowledge that we have of how to run these tests, getting down to $200 by the time that we're at scale, definitely before 2028, is very, very achievable. One thing we get asked quite a bit is: Is that dependent on a reduction in sequencing costs coming down?
It's not. Anything that, where we can reduce sequencing costs even further, that's going to be an additional, you know, reduction from the $200 COGS. But, yeah, I think the roadmap that we've got, we're very confident that we can get there, you know, in a relatively quick pace.
Do you have an ability to pull forward any of those reductions if there is some volatility around reimbursement?
We potentially do. Again, some of that's going to come from volume. But you know, we're pushing hard on automation, and I think the sooner we can get that in place, the sooner we can take out the labor costs and have a very, very efficient lab. It's gonna bring that forward. So yeah, hopefully, we can do that as soon as possible.
Maybe just talk a little bit about, I guess, go-to-market. Obviously, you're heavily skewed toward oncology, but how do you think about the primary care, you know, market and opportunity there?
It's been a new experience for us two years ago. Now, we are two years in market with small team, just promoting Shield LDT now since May of 2022, and we are very happy with what we see. We made some adjustment, frankly. We learned some stuff throughout the last two years. We optimize our customer experience, we optimize online ordering. We have now national-level phlebotomy networks to support this Shield IVD post-FDA approval and so forth. But what we are seeing is when PCPs are adding this Shield in their menu, right now as LDT, in future as IVD, they are just seeing higher overall compliance to cancer screening. We are just seeing it left and right.
We even have some now randomized studies, for instance, in Kaiser, that has proven that in a 2,000-patient study, that the rate of screening can go up significantly if you offer Shield as a choice. So we feel very confident how the Shield can get added as a new choice in a menu with, for instance, stool test. Even if you have a big S&M engine behind those stool tests, they cannot really... If they want to solve the problem of unscreening during last 10 years, they could have made progress faster. So we believe, you know, we can really open up that market opportunity of 50 million unscreened patient with this blood test. That's the modality which would enable it, but we have to go at it step by step. We are gonna be under, doc. We are just gonna have 100 people in the field.
We are not gonna have, you know, 800, 700, 900 people in the field, but we are gonna be very, very targeted, too. We are not gonna win all the accounts right off the bat. We are gonna launch in a very targeted way, and I think we are very excited to see what we can print few quarters after this IVD launch.
On the competitive front, you know, it sounds like Freenome's trying to work with the FDA to go back and rerun those samples. I don't know if you, you know, have a view on whether that's gonna work, but then also, obviously, we're gonna get Exact Sciences, you know, data in October. Maybe just touch a little bit on how you think about the competitive landscape and, you know, what you're watching most closely.
So in general, the liquid biopsy field, as you're well aware of, Tycho, has been very populated always. Even 2012, we were competing with some companies. Like, you know, right now, we are competing with bunch of companies. There are a lot of claims-
... versus real products out there. In the liquid biopsy in general, it's a hard science. Even Guardant 360 after nine, 10 years, still the second other player in the liquid biopsy. They cannot replicate the performance of 360. They cannot replicate the turnaround time of 360, as an example. So, you know, after many years of experience in liquid biopsy, a lot of investments and top-notch talent that we have, this is not easy to replicate. I think we feel a lot more comfortable with the competitive position that we are today than even the beginning of the year, frankly. About some additional competitive readout, let's bring the readout out finally.
You know, samples cannot stay in freezer forever, so, but we feel very confident in terms of where we are today, and we see if we are gonna have a second player in this market at all or not. But definitely, we are gonna have very long time advantage.
Let's maybe shift over to Reveal and kind of indication expansion. You have data submitted for publication around surveillance, you know, the LCD for CRC. Just walk through the impact here of, you know, what the LCD could do to ASPs and margins, and how do you think about that opportunity overall?
Yeah, you know, we're looking at 2025 as being a real inflection year for Reveal. That's primarily gonna be driven by ASPs and, you know, we've submitted data for publication from COSMOS. If we get that published, then we can submit to MolDX. So hopefully we can get CRC surveillance coverage from Medicare, and that would have a nice boost to ASP. You know, at the same time, we've got another focus on COGS on Reveal. We're looking very much at the workflow and how we can take advantage of the Shield platform that we built for a low-cost test, and use that into Reveal. And again, we're targeting 2025, where we see we could have significant reduction in cost per test.
In fact, moving to this Shield low-cost platform could basically take, you know, half the costs out of out of Reveal. And then, of course, you know, driving volume again is gonna reduce the cost per test. So, you know, we're looking at 2025, where if we've got improved ASPs, we've significantly reduced the cost per test. We're gonna flip from having a negative gross margin test to a positive gross margin test, and that will first of all, allow us to really push hard on the volume. You know, we've been holding back on volume over the last couple of years because it's been gross margin negative, and it's, you know, it's costing us every time we run a test, so we can really push hard on the volume.
Then also, it'll have a major impact on our cash burn as well, because at the moment, you know, we're investing this year something like $100 million in MRD, and a large portion of that is coming from running these gross margin negative tests. So if that, again, flips to gross margin positive, it's gonna significantly reduce our cash burn almost, almost overnight. So yeah, we're looking at ASPs, COGS reduction. It's been a real inflection point for, for Reveal in the, you know, relatively near term.
Are you able to give us just any, framework around how you think about ASPs landing, given the number of, you know, new indications you're targeting for reimbursement?
You know, at the moment, and we've said publicly, ASPs for Reveal are just north of $500. You know, I think... And that's basically just on CRC post-surgery, Medicare coverage. The majority of our volume is actually CRC surveillance, so you know, we think we could have a nice lift. I don't specifically want to put an exact number on it, but I think we'll have a nice lift in ASP, given that it's the majority of the volume.
Got it. You're confident in break even then for 2025 on that?
We're confident on a gross margin positive test-
Okay.
I think, and significantly reducing the cash burn. I think, you know, MRD getting to break even might take a little bit longer to cover the R&D and the sales and marketing expense, but, it wouldn't be too far away from that.
We'll shift over to 360 and then maybe wrap up with some questions on cash flow. But on 360, so ASPs, you know, have been strong. You benefited from the increased ADLT rate to $5,000. Maybe just talk a little bit about ASPs moving forward, and is that a ceiling? Is there any kind of juice to squeeze beyond that?
I think there's still some juice to squeeze. You know, we've had a nice uplift. Now we're at this $2,900-$2,950, and there's a few things that have come together. One was, yeah, getting the Medicare LDT rate from $3,500 to $5,000 in the first of January. And we're starting to see the impact of the commercial, additional commercial coverage that we got last year for Guardant360. That gave us a nice upside in Q1. I think what's not baked into our ASP at the moment is the potential uplift that we'll get from Medicare Advantage related to the LDT. So Medicare fee-for-service has moved to $5,000. We would expect, you know, the Medicare Advantage for LDT to start to move upwards. We've not seen that yet. It's gonna take some time.
So I think there's potential for upside there. And in the longer term, you know, we've still got some coverage gaps from the commercial payers for Guardant 360. You know, most all of the national payers now cover, but they don't give us full coverage. So some covering the CDx, some the LDT version, some are covering only, say, lung and breast. So I think there's the opportunity to expand the coverage with some of those national payers. So yeah, we think we set at our Investor Day back in September, the target of a $3,000 ASP by 2028 for Guardant 360. I think we're well ahead of schedule to get, to get there, so we think we can go beyond that.
Maybe in the last couple seconds here, you know, you got it to $300 million burn this year, $200 million next year on Shield. I guess, talk a little bit about the ability to throttle or the willingness to throttle. Like, would you push out cash flow break-even in 2028, you know, if the investments were warranted and Shield had, you know, potentially more potential in the near term?
You know, I think we're committed to the $200 million burn on screening. And again, I think that still enables us to invest heavily on the commercial side. And yeah, we see therapy selections now cash flow positive, that can just continue to improve. I talked before about MRD getting to break even at some point in the relatively near future and starting to generate positive cash flow. So now we feel confident around the 2028 timeline for break even. In fact, where the way the ASPs are moving for Guardant360, potentially we can bring that forward a little bit, while still, you know, investing heavily, but ring-fencing the spend on screening.