Great. Well, welcome everybody. Good afternoon. I'm Matt Sykes, Life Science Tools and Diagnostics Analyst at Goldman Sachs, and I have the pleasure of welcoming Guardant Health here with us today. We have Helmy Eltoukhy, the chairman and, and Co-CEO, AmirAli Talasaz, the Co-CEO, and Mike Bell, the CFO. Mike, AmirAli, Helmy, thanks for joining me today.
Thanks, guys.
Appreciate it.
Thanks for having us.
Maybe we just start out, focusing on your Q3 results, which were very strong, driven by very solid results in therapy selection. Maybe just walk us through some of the high-level takeaways from the quarter after you've kind of digested some of the feedback and conversations you've had with investors.
Yeah, no, we're very pleased with the results we had. We've made progress really across all aspects of our business. We continue to make progress with therapy selection, both in terms of the clinical testing and a huge bright spot for us, which I think is pretty singular, is the biopharma business where we continue to see really strong engagement with our biopharma partners. We had 170 biopharma companies that quarter, and we're seeing essentially them using us really across the board in terms of their programs, thinking about these more complex signatures and thinking about things like molecular response. We see we saw great progress in therapy selection where we continue to make really strong connections through EMR integration, through commitment to data. We hit 500 peer-reviewed publications. And then MRD, we submitted our data for the surveillance indication for CRC.
We have breast not that far behind, and we continue to see that we are a sort of singular, our place is very singular in terms of being able to help those patients, those 15 million cancer survivors, of which 12 million are five years out from surgery. We are really the only company, the only solution that is there for them to give them peace of mind in terms of detecting recurrence from cancer. And then obviously we had spectacular progress around screening in terms of the New England Journal of Medicine publication and really making a lot of progress there to finally get that through the final stages of FDA approval.
Got it. And I'm not gonna wait too long to get into the other big event, clearly a very positive decision in terms of the vote from the AdCom for Shield. Could you maybe how we start out, like, what were your expectations going into that prior? What were you surprised by that happened during that? And then sort of post that, sort of like next steps and how we should think about it. And I've got a couple more questions you can imagine on it, but maybe start there.
Yeah, sure. So first I start by saying how proud I feel with the preparation that the Guardant team went through and really how well they represented Guardant Shield and I think frankly even the whole field of liquid biopsy on that day. I think that would be a memorable day for the whole field for many, many years to come. You know, in terms of our expectation, we had a proposed indication of use, which we had some good clinical and scientific justification that our indication of use is very well- suited based on the performance of the Shield that we saw in our pivotal study. But as you know, whenever you go to these kind of advisory panels and you talk to 9, 10 people just in a matter of one day and few hours, there are some aspects of, you know, unknown unknowns that could happen.
I think we went with the mentality of trusting the process, which contained our presentation and I think a solid deliberation by the team around the pros and cons of using blood tests in this field. At the end, ended with very strong positive recommendation by the advisory panel for approvability of Shield and, you know, in the proposed indication of use that we had, which was for first-line CRC. We were very excited about that.
Got it. Maybe talk a little bit about how sort of, your expectations going in for advanced adenoma. I think you were very upfront during the AdCom about, about what your thoughts were on that, but just talk about, how we should think about advanced adenoma as part of label or warnings, etc., that, that might be attached to that and what you're thinking about on that.
Yeah, we've been very conscious about it during last many quarters about the fact that, you know, the Shield based on the data that we have is really kind of add value in CRC detection and CRC screening for cancer detection. Cancer prevention is a very important subject, but that's not gonna be the goal of this test at. And we are gonna have limited contribution for cancer prevention. So, in fact, our proposed label, we even proposed a limitation that, you know, Shield has a limited sensitivity for detecting advanced adenomas. At the end, we are detecting 13% of advanced adenomas. It's that's what it is. And, you know, having a specific limitation about this matter is something that we've been very proactive about.
Got it. And maybe just talk about sort of the discussion that took place around first-line versus second-line. Obviously the vote, you know, was about first-line, but in terms of like what you thought about the debate and where do you think it should stand and how does the market size change if it's first-line or second-line, understanding that what the AdCom said was, you know, first-line, but I just wanna kinda get your view of the sensitivities around that decision.
Yeah, sure. So as part of the process when this 7-10 people gather, as part of the process, and the agenda is for them to deliberate about the good and bad of the data and the intended use statement that they're getting, faced with. So the agenda for that deliberation is debating and talking about all the positive and negative things that they think need to come on the table. And at the end, try it's the process ends with a transparent vote around safety, efficacy, and the risk-benefit balance for the proposed indication that that AdCom debated around. At that time, I think the voting would be very clear and, crystal clear in terms of what, what they were thinking in terms of, yes or no about bunch of these answers.
So now, in terms of like the topics that got discussed, which some of them actually we are in agreement, I think there's been a bunch of reservations around the impact of blood tests with colonoscopy rates. And I think some of the points where blood could be so good and so easy that many people do blood testing and then we don't do any colonoscopy and kind of exaggerating, and then that could be harmful. I think a bunch of conversation about, you know, majority of I think rational conversation around debate that should be first-line or second-line was about preservation of the value of colonoscopy, which we are in agreement. Colonoscopy is a different kind of device. It has a different kind of intended use. It's interventional. It's a prioritized option if people are willing to go through it.
The reality is majority of people are not willing to go through it or don't have access to it, and that's the place for non-invasive in vitro diagnostics. The conversation about first-line and second-line really is between the tests within that category of non-invasive tests, which effectively becomes our blood test and stool test and other blood tests that got approved by agency many years back, versus I think concerns about preservation or substitution of colonoscopy. Now, in terms of market opportunity, when we look at average risk CRC screening, there are 120 million people in the U.S. in that age category that, based on guidelines, it's recommended for them to get screening. First-line label allows marketing and promotion of the test toward all 120 million people. In reality, as I mentioned, colonoscopy is a prioritized option and 55 million people are getting screening by colonoscopy.
We are not seeing a lot of evidence in the commercial world that people are willing to replace colonoscopy with non-invasive tests. So really the commercial opportunity for first-line test from our perspective is 65 million people, out of which 50 million are unscreened , which are eligible for second-line label. So it's a market size of 65 versus 50, first-line and second-line. Still, we prefer this first-line in terms of the roadmap for some indication expansions that we have in mind for Shield. There's gonna be some good advantage for us to continue to secure this first-line label for us versus second-line. But within the CRC market, that would be the impact of 65 versus 50 million.
Got it. And has what you heard at the AdCom at all changed your view in terms of the spend that you're willing to put towards Shield? You haven't changed anything in public forum, so, but I'm just wondering if that has all affected how you think about it.
So we continue to believe this brand is gonna be one of the biggest diagnostic brand ever existed, if not the biggest. And again, even for starting with 50 million people, that's 16 million annual testing opportunity. That's $8 billion TAM opportunity. At 65 million first-line, that's about $12 billion market opportunity. We continue to believe this market opportunity is very big. We just need to make sure we get FDA approval. If we can't secure FDA approval, we are gonna have some serious conversation in terms of material adjustment, in terms of our spend and operating plan. But we have strong conviction that we are on the right path, even the right path for a good label. So, but we'll see at the end when FDA finalizes their decision.
Last question on this, and again on spend. You've talked in the past about blood tests given the adherence, spend might not have to be as much. Could you, could you see yourself kind of ratcheting down spend as you see that adherence taking hold? And is there any sort of gating measures you're using for spend outside of obviously the approval and things you've talked about in the past? But I'm just wondering how often you're gonna be thinking about that spend over time as you roll out the test post potential approval.
We have some milestone and phase gate that we've defined. For instance, one of them was this favorable outcome. Then the next one is FDA approval. And as we launch then getting into ACS guidelines, showing the revenue, showing the market traction. As long as we are meeting those milestones, we are gonna continue the investments with the ring-fenced spend that actually we talked about before. But it's not that under all scenarios we are gonna continue this investment. As long as we are meeting those milestones, the next round of financing is gonna get released for continuation of building this brand. Now, I think with this level of net burn of $175 million, $200 million next year, we are adequately resourced. And that's a fair question that, okay, why historically took much larger investment for stool-based tests? I point to two main issues.
One, our understanding of the market is for stool tests, there's a lot of pushing to market that needs to happen for patients and providers to use stool options. Seven out of 10 people who've done stool tests do not wanna do it again if they get other options. Versus blood testing is so easy, so convenient that in fact we are dealing with the concerns that, hey, maybe it's gonna be too easy that we are worried about colonoscopy, right? We have a different kind of issue. So S&M efficiency would be much higher. So, you know, related point, when stool test commercial engine sells like three tests, three stool tests, more than often one out of those 3 tests never come to the lab and as a result does not become billable. For blood test, almost all ordered tests would result into billable cases.
That's all translates into more favorable unit economics and more favorable S&M engine to produce billable cases. I think the last point I make about this spend is we are leveraging a lot of scaled infrastructure that Guardant Health has. Like the G&A function of Guardant is we are really like, almost paying it for the, you know, profitable core business for therapy selection that we have, but we are leveraging that core infrastructure and some other infrastructure at Guardant. So as a result, we can have much better margins over time with our screening business.
And how should we be thinking about COGS? I know you've stated in the past the 1 million sample is like $250, but that's not where we're gonna start. But how should we think about, you know, Mike, how should we think about COGS for Shield in this sort of early period of time?
Yeah, you know, very, very quickly, after launch, we'd expect to get the COGS below $500. And we've, you know, we've said once we get an ADLT rate, then, ASP would be above $500. So very, very quickly we'll have a positive gross margin with Shield. And yeah, we've, we've said over time, and by the time we get to 2028, 1 million tests per year, then the cost per test will be, will be $200. And we've got a, I think we've got a very strong roadmap to get us from that $500 to $200. Obviously, a lot of that reduction will come from just increased volume. But, you know, we're very focused on the workflow. We've got a lot of efforts ongoing around automation. And, you know, within the company, we've got some very experienced people who've built, you know, large-scale automation at very large-scale labs.
I think we know, we know how to do this. Yeah, we're, we're confident that, you know, over time we'll get that cost per test down to $200.
Got it. Helmy, coming back to you on, on therapy selection, you've got a sort of a implied guide of sort of a step up of 20% in the second half for clinical volumes. What are some of the key drivers of volume growth? What's your sort of level of confidence in that? What's sort of the visibility into that?
Yeah, no, we're very pleased with the start of the year. I would say that a few different, sort of vectors we have for the year, really, improving the experience in terms of the ordering aspects, the digital integration, EMR integration. That's been going really well. Partnering with centers really top-down, doing sort of a key accounts function. I think we announced a partnership with McKesson and will hopefully announce, you know, a few more, as time goes on. And then, you know, really the products that we're bringing to market. We just launched, essentially an upgrade to our tissue product last week, expanding that to 500 genes. We'll have obviously the rollout of smart liquid biopsies second half of this year. I can tell you that at both AACR and ASCO, we had just so much excitement and engagement around some of these features we're bringing.
Really, the fact that with this full epigenetic backbone, we're able to see insights into disease that is even very difficult to see with tissue testing. We're able to see transitions in histology of the disease from adeno to neuroendocrine, like things that are just very difficult to track in terms of the landscape, seeing things like cardiotoxicity, liver toxicity with this platform. And then that's just scratching the surface, basically more immuno-oncology applications, HRD applications, and so on. And so, for the first time we sort of gave a sneak preview at AACR last month. And I can tell you, we're seeing engagement with academic centers that remind me of when we first launched Guardant360 back in 2014 in terms of really the initial promise of liquid biopsy.
And so we're very confident that we can re-engage essentially the top centers and really rekindle that excitement about the sort of next big thing in liquid biopsy with our smart liquid biopsy platform.
Got it. I do wanna focus on the EMR integration efforts because.
Yeah.
A lot of companies talk about them. They're actually really significant, very difficult to kind of do, but once they're embedded in there, they're a huge tailwind. Could you maybe talk about how sort of like, how much of that work is remaining, how much sort of additional runway you have on that, and when we should start, if we haven't already, start seeing that uplift from that EMR integration work you've been doing?
Yeah, so it, it depends on the vendor. Some are sort of SaaS platforms where once you turn the switch on, it is rolled out across their install base. And others like Epic is really a one-by-one sort of blocking and tackling exercise where we have to turn switches on at each center successfully, successively. And, and I can tell you that, you know, Epic is, is certainly worth it in terms of the initial results we're seeing where, because the whole center is engaged in terms of that process, there's a lot of awareness that so essentially Guardant is coming to their, to their platform, to their system. And so we tend to see an uplift of volume even before we turn things on just because of the level of sort of visibility that we have.
That's an area where we're still in the early innings in terms of Epic integration, probably less than 20%. But we're essentially doubling our efforts there in terms of increasing the funnel and increasing the queue so that we can go more quickly there. But others like OncoEMR or iKnowMed, we're sort of well through most of the heavy lifting there.
Got it. And then shifting to Reveal, could you just maybe give us some of the, some of the key updates in the last quarter from that? And then some of the key catalysts you're waiting for in order to push harder on those Reveal volumes and CRC surveillance, but maybe just remind us kind of what you're looking for in order to start really pushing that.
Yeah, look, we're really heads down in terms of getting that surveillance reimbursement indication. Right now we have CRC in the adjuvant setting. But the utility of a sort of tumor agnostic approach, a blood-only approach, is really in that surveillance setting.
Yeah. Essentially all patients that are 1 year out, up to 5 years, 7 years, and so on. And that's really where the majority of, you know, patients sit today. And so we are, you know, hopefully, you know, a few months away from having our CRC surveillance publication out there. As soon as that gets accepted, we'll be submitting that to Medicare for reimbursement. And we're hopeful that by end of this year, early next year, we'll have that CRC surveillance reimbursement. Breast is probably a couple of months behind that in terms of timeline, and we're very excited with the data that we have there. Those two indications alone in the surveillance setting are probably something like 4 million-5 million of the 12 million patients that are 5 years out.
So, that would really make up a sort of, really a big part of the potential reimbursement for our MRD franchise. And then the third sort of thing that's happening, at the same time is a really major COGS reduction initiative we have in terms of a platform. We think we'll be able to reduce COGS by 50%. And so we'll see a sharp sort of crossing over of the lines, ASP growing up, really significantly when we get those two indications, and COGS going down very significantly. And all of that should be in place by sort of, you know, first half of next year. And that's really where we can start really accelerating volumes because now we'll be positive gross margins and that'll be accretive to our bottom line.
Could you maybe this question for Mike, would you dig in a little bit into that COGS reduction and Reveal and what steps you need to take and, and sort of what you're really attacking on that?
Yeah, I mean, the main focus is really leveraging a lot of the platform and the learnings that we've had from the low-cost Shield platform and just moving the Reveal onto a similar platform. So if we, you know, if we can do that again, it's gonna significantly reduce the cost per test. I think the other driver that then we'll see on top of that is once we start to push on the volumes of Reveal, that's gonna have a further impact on reducing the cost per test. So, yeah, we're excited to get that in place. The team working very hard, back at Guardant, you know, developing that.
And yeah, as Helmy said, if, if that comes in the first half of 2025 along with ASP increases, then it changes Reveal dramatically.
Got it. And Helmy, just for Guardant360 in the U.K., your recent partnership to expand the NHS study, could you talk about what kind of impact that can have? And you've done for your sort of international European strategy, you've done a lot of these types of partnerships. And that's sort of the, it seems like to be the preferred way you're, you're doing things, but maybe talk about how NHS itself might have an impact. And then just talk about your international strategy in general.
Yeah, no, I think the U.K. is one of those markets, if you can make it there, you can make it anywhere, right? That's just the most challenging in terms of pricing. And so we're very excited with the success we've had there now. We essentially decided many years ago to invest there, in a way that sort of made sense with the reimbursement framework that we saw developing there, which is build a lab sort of inside that ecosystem and, in one of the leading centers in the U.K., the Royal Marsden and essentially go to bat with those top KOLs in terms of really deciding how that technology should be integrated into their healthcare system in terms of how it can help, specifically, you know, the patients over there.
And so we're, this is now really a model of success that we wanna essentially use in all of the EU 5 and multiple other countries around the world. And what we found over there was that because of some of the challenges in terms of how lung cancer patients are diagnosed, how they're treated, was taking 4 months for the average lung cancer patient to actually get on treatment. Keep in mind that the average life expectancy of a late-stage lung cancer patient is 11 months. We did a pilot there and we found that we're able to cut that down to just a couple weeks in terms of, you know, when you use liquid biopsy in that setting. And so obviously they were very excited, the NHS, in terms of, you know, the promise of this.
We're rolling it out to essentially 10,000 lung cancer patients and probably it'll roll out to all lung cancer patients over the next couple of years. They wanna expand this to other cancer types as well. And so quickly the U.K. went from, you know, a small market to a, for us to one that is, you know, maybe as large as Japan potentially in terms of the sort of, you know, revenue potential and testing volumes. And we're seeing that model, really, we're seeing a lot of other countries take note. We have a lab in Spain that, you know, I think is progressing, and potentially discussions around many of the other countries in the U.K. and certainly Middle East and other places. So this is really, you know, the international has been a, a challenging, I think, aspect for a lot of U.S.-based diagnostic companies.
This is really one of the initial models that we've seen finally work and finally take off in terms of being, sort of a profitable, profitable model that's accretive to the business.
Got it. Maybe more of a higher- level question, the FDA LDT regulation. Could you maybe talk about how that impacts your business? You know, is, is there a certain percentage of tests that are approved, not approved by the New York State pathway and things like that that sort of make it, fine for you? And I mean, my personal view is that I think it's really good for the incumbents, might be challenging from the innovation side, but I would love to get your thoughts on that LDT regulation and how Guardant factors into that.
Yeah, I mean, frankly, we were, I think, well equipped no matter how it ended up just because, you know, we do have tests that have gone all the way through FDA approval, with Guardant360 and, you know, knocking wood Shield, you know, soon. And, you know, I think, but the way that it ended up, you know, virtually all of our tests are New York State approved. We're a national lab. New York is an important state. So for us to not get approval there, doesn't make a lot of sense. So it's become something of, I would say, you know, kind of a not much of a big issue, you know, for us.
But, yeah, it'll be interesting to see, you know, how this sort of ends in terms of some of the reporting requirements and so on, which will add a little bit more complexity to testing. But yeah, it's really something that's not gonna affect our business really in any way.
Got it. And then Mike, just maybe talk a little bit about sort of dealing with cash collections, reducing no pays, sort of the whole revenue cycle management, which has been sort of a greater focus for the diagnostics industry over the past year and a half and how you have kind of set that up and are dealing with that.
Well, I'd say we've been very successful with the reimbursement, how we manage the billing. We've got an incredibly strong team, Guardant, that manages that, and they've been doing that for many years. And I think, you know, that on top of the tailwinds that we've had on ASPs over the last year or so have really helped drive our gross margins and our bottom line. And, yeah, our cash collection is very strong. Maybe just to touch on the ASPs for a moment. You know, we saw great tailwinds with Medicare, increasing the LDT rate from $3,500 to $5,000 at the start of the year. We've had really good tailwinds from the collections that we've had from commercial payers.
We got this additional coverage from some of the national payers, 12 months or so ago, and that's really coming through now. And again, the billing team's doing incredibly well in collecting that cash. And going forward, I think there's opportunities for us with Medicare Advantage related to the LDT and starting to see an uplift on the Medicare Advantage rates that we get paid. And there's still gaps in our commercial coverage for some of these national payers. So I think there's a huge focus still within the business on cash collections, but also improving those ASPs even further.
Got it. And then maybe just talk about your reduced cash burn guide for 2024 and some of the drivers that are there and how we should expect that as we move into 2025.
Yeah, I mean, there was, there's effectively two drivers. We reduced the cash burn sort of $40 million-$50 million compared with our guidance and something like $60 million compared with last year. The change in the guidance was driven by two things. One is the uplift in ASPs that we saw. And, you know, we increased our ASP guidance for Guardant360 to $2,900-$2,950. And that's effectively, it was $15 million-$20 million upside on revenue, but also that falls down to the bottom line. And then the second element to reducing the cash burn was on the screening side. So, you know, we gated the spend at $200 million. Because of the pushback of the AdCom, we just held back some of the commercial expense and we brought that down to $175 million maximum this year.
How should we be thinking about the balance sheet? Obviously you've got a strong balance sheet. There is debt on the balance sheet as well. How should we be thinking about it over the next few years?
I think from a cash perspective, we ended last quarter with $1.1 billion in cash. So we feel in a very good position. That can get us through to our break-even target. We said that would be at our investor day, we said that would be 2028. Where are we going with ASPs on Guardant 360? We could even bring that forward a little bit. But we feel that $1.1 billion is more than sufficient to get us to what we talked about on the screening side. $1.15 billion, it matures end of 2027. So we've got another 3.5 years and it's a 0% coupon. So, that's nice to have on the balance sheet. You know, we know that before end of 2026, 2027, we're gonna have to address this.
I think we look in all the time at what ways to do that. I think, we've got a lot of optionality and we've got a lot of time to be able to do that. So one thing we don't wanna do is let the convertible become an overhang on the balance sheet. We wanna manage it well and we wanna be proactive in doing that. But we're not feeling any urgency or pressure to do anything, you know, immediately.
Okay. And AmirAli, I wanna go back to you on Shield. USPSTF is obviously some time away, but certainly a topic of discussion in terms of interval. How are you thinking about that, as you, as you answer these questions from people? But how, how are you thinking about that dynamic?
Yeah, sure. So, you know, keep in mind just the FDA approval would open up people at age 65 and above completely. That's a huge market by itself. So we have a lot of business to mind and grow in that patient population while we are waiting for guidelines to take action. We are also excited with American Cancer Society guideline. We are in conversation with them. We know they've been monitoring our field very, very closely. We expect, you know, to get FDA approval, you know, sometime this year and go, in, you know, get recommended by ACS sometime next year, 2025. That would give us actually a lot of interesting opportunity. There are 10 states that have state-level mandates for local payers to cover colorectal cancer screening tests as long as they are recommended by ACS.
That's gonna open up access to younger patient population in 10 out of 50 states in the United States. Then we are gonna wait for USPSTF. We continue to actually be very positive about what could happen there. Again, keep in mind 50 million unscreened patients. 76% of the colorectal cancer death is coming from the people who are not up to date with screening. Now there is a blood test that people easily do that is medically like cancers at curable stage. What do you think is gonna happen? I'm very excited to see those days, so.
Okay. And then just, before we leave, one thing that hasn't been discussed a lot lately is Shield LUNG and sort of the updated timeline for that. Maybe just kind of remind people about what the work you've been doing there and what the timeline is for that.
So our vision at Guardant from our founding days was a simple blood test and a cure for cancers and Shield your body against this disease. Guard your body against this disease. And CRC was our lead anchor indication to make sure we find a reimbursable pathway to make sure people would get access to this blood test. So once we get FDA approval, we are gonna be on a task to add indications to Shield tests. A strategic indication for us is lung. We are doing a second cancer screening study, over 10,000 patients. We are in the third year of enrollment and we are very excited with actually the progress that we are making there. But we don't expect to do these kind of trials one by one.
You could imagine a panel of multi-cancer detection altogether would get added to the same Shield test that people would get access to because they are gonna use it for CRC screening. We are very excited about what could be the future of Shield in the era of multi-cancer detection.
I think it's a great place to stop. Guys, thank you so much for your time. Really appreciate it.
Thank you. Thank you.