To kick things off for our next session. Thanks, everyone, for joining us. My name is Mike Ryskin on the Bank of America Life Science Tools and Diagnostics team. For our next session, we're excited to host Guardant Health. We're joined with AmirAli Talasaz, Co-Chief Executive Officer, and Mike Bell, Chief Financial Officer. AmirAli, Mike, thanks for joining us. Thanks for having us. Just to kick things off, I don't know if you guys have any opening remarks, or maybe you want to opine on how the first quarter played out. We're very excited actually, how this year started for us. We had a great Q1, and we are looking forward to a bunch of activities in the very near future, including this AdCom, which is gonna happen for Shield next week. We are going there excited and confident. In general, we are looking at this year as a very great year when you look at actually two brands with huge potential, Shield and Reveal, can go from a gross margin negative product to gross margin positive products in, near future as we go to next year. It could be transformational for us, and our core business is growing, you know, solidly, and we are very happy with our position there and the market dynamics there. So we are very pleased. Maybe I'll just jump in a little bit on the first quarter, walk through some of the points, then we'll move on to the AdCom and Shield and Reveal. Just on the quarter, you know, you had a really impressive beat, well ahead of the Street. You raised the fiscal year guide. I mean, it was pretty broad-based, you know, both on ASP and volumes. Just on the volume side of things, you know, anything in particular that drove it? You called out a small cash collection, you know, $8 million benefit, but even excluding that, it was really strong. So just speak to the underlying strength. Well, yeah, I mean, underlying strength across, across the business. You mentioned, you know, the ASPs for Guardant360. You know, we had the uplift at the start of the year because we had the Medicare LDT rate going to $5,000, but then, you know, on top of that, we saw really good traction with commercial payers. So that led to actually a, you know, one-time true-up from Q3, Q4 last year of around $8 million. But, you know, the increase in the-- the main increase in our guide was driven by Guardant360 ASP. So, you know, we've increased that, the range of ASP there to $2,900-$2,950. And for the full year, you know, that, that leads to something like a $10 million upside. But as well as Guardant360, we actually saw really good traction with ASPs on TissueNext, Reveal, and Response, and that's really coming from the commercial payer side. So I think, you know, a lot of the work that the team's done in the past is starting to really drive, drive the top line now. And then, of course, when we get increased ASPs, that's flowing down to the bottom line, and we were really pleased to be able to reduce our cash burn for the year. And, you know, that was coming from, one, a reduction in our spend on the screening side, but then just as much was coming from the ASP upside and the upside that we're getting on the revenue. Now a great, great start to the year, and I think we see potential upsides even on the ASP as we go further into the year. Yeah, I mean, just on that point, Mike, the ASP that you called out, the $2,950, like you said, nice strong jump in the first quarter, but it seems like there's a little bit more upside potential through the rest of the year. You're not baking any of that in right now. How could you see that develop over time? Yeah, I think we, you know, we always want to be conservative on how we set those ASPs each quarter. I think the biggest potential uplift that we've got is related to this Medicare LDT uplift. So we had the, again, the uplift to $5,000 from what Medicare pays us. What we didn't bake into that, that Q1 increase was the potential to get additional reimbursement from Medicare Advantage and the commercial payer. So you know, hopefully, they'll sort of follow suit and be paying sort of close to that Medicare $5,000 rate for the LDT. And if that comes through, and sometimes these things can take, you know, a few quarters, but if that comes through, then that'll be a nice, you know, additional upside. So again, we're, we're working hard on that, and, yeah, it could be a nice upside. Okay. Let's move on to the AdCom for Shield. Like you said, it's coming up very soon. A lot of anticipation there. Last I saw on the website, and I'll be honest, I haven't checked in the last couple of days, there were still a few seats open. I know you know, the delay earlier in this year was because they couldn't fill the seats. You know, just doesn't need to be 10 out of 10, right? It is sort of a, there's some judicial, you know, freedom there. So you're comfortable with the proceeding next week? We imagine the panel members would be there. We are gonna be there, so we'll see. Actually, well, as you know. The AdCom is gonna happen next Thursday- Yep. and we are very excited. We are prepared. In terms of the membership, apparently, our understanding is there are some kind of committee members that they are assigned for two, three years. They are official members. They- their name shows up on the website, and then sometimes they add temporary committee members- Mm-hmm. -which are just for that specific AdCom for that specific topic, and apparently, those names do not show up on the website. But we are gonna know the name of the panel members actually couple days before the AdCom too, but we imagine everybody would be there. Okay. That's a, that's a relief. That's step one, is actually having it. And then in terms of your expectations going into it, I mean, a lot of debate in terms of what will actually be the outcomes. Just right now, you know, what are you looking for? What we need is to get FDA approval for Shield. We have good. We are continuing to make progress with the agency in this interactive review process. The tone continues to be very positive, supportive, collegial, collaborative kind of interactions we had with them, throughout, you know, last year and a quarter. We expect to get this to the finish line and get FDA approval. That's what we need to really build a solid brand and have a successful Shield launch later this year. But we'll see actually how the outcome goes next week. Again, we are going there excited, well-prepared, and confident. In terms of, the label itself, I mean, we're getting a lot of questions on first-line versus second-line. I think you talked about in the past about, you know, the market opportunity in the near term is not going to make a difference, but still, could you talk us through, you know, what are the factors that would lead you to one versus the other? So, maybe I can put this in context in terms of commercial opportunity, but first-line means what second-line means. Mm-hmm. So, there are 120 million average-risk individuals in the United States that, based on guidelines, they have to get screened for colon cancer. So a first-line indication means effectively the test would be a choice for a patient to pick upfront, alongside colonoscopy and other stool-based tests. So effectively, your opportunity is for the whole 120 million people. The second-line means for the people who are unscreened, who are actually declining other modalities, and they are not compliant cancer screening. So our estimate is about 50 million people are in unscreened patient population, so that becomes second-line opportunity. The reality of the commercial landscape, though, is colonoscopy is the preferred modality. Like when you talk to the doctors, when you're looking even at the market trends in terms of adoption of non-invasive CRC screening versus colonoscopy, colonoscopy has its own share, and we are not seeing any kind of evidence of replacing colonoscopies and doing more stool-based tests. There are 55 million people today that they are getting screened by colonoscopy. So effectively, out of 120 million, there are 65 million, which are the reality of first-line commercial opportunities, since colonoscopy always would be number one in terms of preferred choice by physician, in terms of conversation and recommendations. So first-line would be 65 million, and second line, our assessment is gonna be about 50 million people. That's why we are really focused to make sure we get the FDA approval. Having said that, what we are asking for is, and our proposed indication is the first- in the first-line setting, and the indication of use that actually got published in the Federal Register, which is gonna be part of conversation next week, is for Shield to be used as a first-line device and test. We believe there are scientific merit with it, about it, clinical merit about it. We've done a first-line clinical study. Our performance is in range with other first-line options, and really, the trend has been toward giving more choices to patients and physician versus restricting access upfront. So we are making those kind of arguments about first-line case, but at the end, we need FDA approval. That's what is the success factor for us at the end of this process. Okay. That's really helpful. And then, appreciate your color on, you know, the patient opportunity between first-line and second-line. What about the reimbursement and the payer landscape? I mean, is there any difference in terms of first-line or second-line approval, where you're more likely to see commercial payers come in or? So what we know in terms of the CMS position right now, the National Coverage Determination for blood-based colon cancer screening requires FDA approval and some certain performance in terms of sensitivity specificity. With the pivotal study that we've done, we are meeting and far exceeding actually those minimum performance based on NCD, and the missing piece is FDA approval. So that FDA approval for first line or second line would make us qualified for National Coverage Determination. And then we have to go through guideline reviews, first by American Cancer Society and then United States Preventive Services Task Force, to see how they're gonna react to the performance that we've seen and the data that we have. So solid performance in range with other kind of modalities that right now are recommended in guidelines. In fact, we are in range. There are some stool tests recommended in guidelines that across all parameters, the performance is, lower than Shield. So we are somewhere in the ballpark and the range of other modalities. Okay. And then, you know, you talked a lot about the FDA approval and the factor there, but you've also got the USPSTF guideline meeting in 2026. There's some chatter it could be 2027, first of all. Any take on that in terms of what gives you confidence in one—it's one or the other, and, you know, how much does that matter if it's a couple of months delayed? Actually, what we know is USPSTF does not interact with any industry player directly, and, you know, so I think any kind of conversation that, you know, information shared about delaying USPSTF is, there's no evidence for it. You know, there is no indication by them that they are planning to delay the process. The last time they did the CRC guidance review was 2021. Based on statute, what they try to do is typically, like, reviewed every five years. What happened for a stool-based case last time, 10 years ago, when they got FDA approval 2 years after they went into the guideline. So our assumption would be, you know, probably seeing the draft research plan by the task force later this year, and then go through the process and hopefully getting included in the guideline before end of 2026. Okay. And then, the other factor I want to touch on here is, as always, there's a lot of noise about other potential entrants, private players, you know, with the, with various readouts. It's really tough to look at the data, because it's not all apples to apples. Every study is a little bit different, so it's really hard to do those comparisons. But you've been really vocal and really confident that, you know, you've analyzed those other tests, you've sent them samples, and, you know, you're confident that, there will be degradation, and that they're not gonna be, you know, they're not gonna hold up to the initial speculation. What gives you that, that confidence, that visibility, and, you know, given the readouts we've seen in the last couple of months, does that view still hold? I mean, our market-leading performance is very clear, right? So I mean, frankly, in our line of sight, we don't see any credible competitor with a blood-based test right now. This is a hard field. Like, the level of innovation that we're talking about is not easy. Just even take a look at the landscape of Guardant360. We launched it 10 years ago. Still, many players cannot even replicate the performance that 360 has in advanced cancer patients. And like, you know, 12 years of R&D has gone in this company. The DNA of Guardant is an innovative R&D company with leading-edge kind of technologies. So just the imagination that somebody talks about it, you know, they're gonna have that level of performance that we've shown, I think is maybe expecting too much from other people. Based on everything that we know today, there is no single assay that we are worried about at this time. We have a very long lead time in terms of first-mover advantage relative to other people. Okay. Let's move on. I want to talk about therapy selection a little bit. You know, it's performing really well, as you talked about, really strong first quarter. You know, 20, roughly 20% clinical growth, you're looking for in fiscal year 2024. You know, anything in particular to call out in Guardant360 from a volume perspective as you move through the year? Yeah, I mean, I mean, first of all, yeah, to reiterate that we expect overall, you know, 20% clinical volumes for the full year. So we were really pleased in Q1 to come out with that 20% clinical volume growth because we know in the first half of this year we've got very difficult comps. Because last year we had the ESR1 approval, and, you know, middle of Q1, we saw this immediate uptick in volume on breast cancer for Guardant360, and in fact, that was, you know, incredibly strong in Q2 of last year. So, you know, as we go through the year, I think, we expect that year-over-year growth will dampen down a little bit in Q2 because of the prior year comp, and then it'll, you know, come back potentially over 20% in the back half of the year to get to the full year 20%. So I think, yeah, we started the year off probably a little bit more stronger than we expected, and so as we go into the remainder of the year, you know, things are looking good for Guardant360, and again, you know, TissueNext performing very well. We mentioned, you know, for Reveal, we're still in a position where we're actively managing the volumes. So again, to come out with 20% growth in the first quarter was strong with all of the things going on. On the topic of ESR1, like you said, it's been about a year since you introduced that. Any color you can provide on some of the feedback, the reception you've gotten? No, I mean, all very positive, but I think, I think the numbers sort of spoke for themselves. Yeah. You know, again, we saw this dramatic uplift in Q1, Q2, and then, you know, since then, we've sort of continued to see growth in the breast volume. So we're off a much higher base now, but it's still growing. And yeah, maybe just to mention, in Q1, we saw growth across all the cancer types with G360. So, you know, breast still doing very well, but all the other cancer types doing well as well. Okay. All right. And then, Guardant360 on the Smart L iquid Biopsy platform, could you provide an update there? Yeah. You know that that's something we're working, we're working hard on. You know, we've effectively, you know, the test works. We've effectively been running this now for last couple of years with Guardant Infinity on the biopharma side. So we're ready to go. You know, there's some hoops to go through on the technical assessment side with MolDX. So we're working through that, but we wanna make sure that we, you know, maintain the $5,000 Medicare rate that we've got for Guardant360 LDT. So, you know, as soon as we get through the tech assessment process with MolDX, we, you know, we'll be ready to launch. So we're yeah, we're really excited about that, and we think it's gonna differentiate Guardant360 even more. You know, it's a competitive environment, so to be improving our test now and being able to sort of launch this sometime this year, we're excited to do that. Okay. Let's move on to MRD and Reveal. You know, you had really impressive growth in fiscal year 2023 and in the first quarter. You know, how are you looking at. You talked about the opportunity to take that from a negative gross margin to positive gross margin. You know, how do you see that transition playing out, and what sort of volumes do you need to hit to get there? It's not necessarily a volume game to hit that, a positive gross margin. There's two things we've focused on. One is the ASP, and, you know, I mentioned before, we saw good traction with the Reveal ASP, so it's improving all the time with commercial reimbursement. But what's gonna be the real driver there is to get Medicare reimbursement for CRC surveillance. And so, you know, we mentioned on our earnings that we've submitted the COSMOS data for publication. So, you know, once we get that published, we'll submit to MolDX. So, you know, hopefully, we can get that in the relatively near future, and that would have a material impact on our ASPs, because a lot of our volume, the majority of our volume is CRC surveillance. You know, one thing to drive that positive gross margin would be the ASP, and the other is on the cost per test side. We're working very hard on the workflow around Reveal, using the Smart Liquid Biopsy platform, using the epigenomics piece of that platform. We think we can have a material impact on the cost per test. That's on track for end of this year, early next year. I think if we get to a position where our ASPs have increased, we've made a material decrease to our cost per test, we'll be in a positive gross margin position, and then we can really push on volumes. Maybe the other thing to mention is with MRD. You know, this year we'll invest around $100 million in MRD. And a significant proportion of that is the gross loss we're making, because we're running these tests at a loss. And once we can flip that from a gross loss to a gross profit, and we're driving the volumes, I think MRD for us becomes a very different prospect, and we'll be pushing on the volumes. But it'll also have a you know, a good revenue impact and a good impact on the bottom line as well. Okay. You touched on some of the MolDX timelines, but you've got a couple of other catalysts. You got a readout of PEGASUS, and then a few other longer-term studies. Just can you provide us on timelines of that and how meaningful any of those could be? So they are all ongoing. Maybe PEGASUS would be sooner than other ones, but they're ongoing. So some of these utility studies could take time, you know. A good fraction of them in terms of patient enrollment, it's in a very good and solid shape, but we just need to follow up on the patient and look at the clinical outcomes. Okay. All right. Any questions from the audience? All right, we'll keep going. Let's talk about biopharma. You know, you've got it for a little double-digit growth. You know, you've got a little bit of an uncertain funding environment, but you're still seeing, you know, pretty strong results there. So any change in how conversations have gone in the last couple of quarters? You know, how do you see that playing out? So I think some of the biopharma weakness that we are hearing in our ecosystem for Guardant, in fact, it was a strong point. So when you look at some of the prioritizations that were happening, and some of the biopharmas, in fact, generate more excitement and investment in some of the testing with Guardant platform technologies to understand some of those mechanism of action faster, so they can prioritize actual investment more appropriately. More important than that was the Guardant Infinity launch. Adding this epigenomics content to what a blood test can unveil for a customer, generate a lot of excitement. Now, over 30% of the pharma volume are Infinity-based and. Correct? Mm-hmm. Yeah. Yeah. You know, we are seeing actually good growth there, a lot of exciting conversation, and a lot of good growth opportunities there. The pipeline conversation continue to be strong, so we are very pleased with the growth that we've seen, and we have a solid pipeline to continue to see some of that growth. Okay. In terms of the international business, you know, you've talked a little bit about some near-term opportunities, in the UK and Japan. You know, you've received a national reimbursement for G360 in Japan last year. Just what sort of growth are you expecting for those regions in the near term? You know, how should that compare to what you've seen in the U.S. historically? Yeah, I'd say Japan and the UK, on the clinical side, are our two big opportunities on the outside of the US. And both are going very well. You know, we sort of commercially launched in Japan, end of Q3, start of Q4, and so we've seen nice traction over the last couple of quarters. It's still early days, and there's still, you know, quite a bit of sort of blocking and tackling that we need to do. But we're, you know. I think we're progressing well, when we're doing as, you know, progressing to the target that we set ourselves. So I think we see, you know, good growth coming from Japan. And the UK, we announced, you know, there was a press release from Royal Marsden, a couple of months ago that, you know, now we're together with Royal Marsden, we're part of this 10,000 patient trial pilot, should I say, with NHS. And, you know, Royal Marsden and Guardant will be taking the majority of that volume, and that's really exciting. I think that can help significantly drive our volume over the next 12 months or so. And, you know, if that pilot's successful, then it can open up to, you know, 3 times that volume in the UK. When are you expecting, either data there or a decision on expanding the pilot? The pilot's gonna go through to March 2025, and it's not specifically data that we're sort of looking for, but it's just, you know, the NHS is gonna assess how that pilot works. And that's, you know, one of the primary drivers of that is really to using Guardant360 as a first-line test at the time of sort of diagnosis, to get the patients onto treatment earlier, and also to reduce the wait times. The NHS has a big issue with wait times, and so if that pilot's successful, and it can reduce the wait times and get the patients on the therapy earlier, then, you know, there's potential they can roll that out for all lung cancer patients in the UK. Okay. Maybe sticking with you, Mike, I wanna touch a little bit on cash burn and investments. You know, you've laid out the $200 million, give or take, for Shield as a- Mm-hmm -as a pretty specific number. Any other factors, and we'd already talked about AdCom and FDA approval, but any other factors we should think about in terms of, you know, as you ramp up EBITDA and as you get closer to cash flow positive? I mean, yeah, I, you know, we, we, we said, we said our sort of guidance over the next few years, that the maximum burn that we would, that we would have on, on screening as we, as we launch this and, and make progress in the market is gonna be around, you know, $200 million a year. But, and we, we're gonna gate those investments, and, you know, we said really based on commercial milestones, and the first one being FDA approval. So once we get past the AdCom, and once we get closer to an FDA approval, you know, we'll start to really invest on the commercial side. But there's, there's other, other gating factors. Getting into ACS guidelines over the next few years in certain states is gonna be a gating factor for us, and USPSTF guidelines is gonna be the ultimate one. So we're gonna ramp up our commercial efforts very carefully. We're gonna be very targeted in our launch. We really wanna focus on driving as much gross profit through the volume that we can, and that's gonna allow us to better invest on the commercial side. So we're gonna manage this very carefully, but you know, we're confident that we can get to a cash flow break even for the company at. We said 2028 at our Investor Day. I think the way ASPs are going on the therapy selection business, that could be, that could be sooner, and of course, we wanna drive the screening business to a cash flow break even and profitability as, as quickly as possible. That's our, that's our overall aim. Okay. And then the other part I wanna touch on was the $100 million investments you laid out for MRD for this year. Just how should we think about the pace there and- Mm-hmm -further investment needed beyond that? Yeah, again, you know, I think I mentioned that, a portion of that is the gross loss that we're making. Another portion of that is the R&D investment that we're making to really reduce the cost per test. And so I think the profile of MRD and the cash burn could dramatically change next year, and it could change very quickly. Again, if we get to a position where we've got a positive gross margin on the test, we've completed a lot of the research and development to get that lower cost per test, then the burn on MRD is gonna come down significantly, and again, that's gonna allow us to continue to reinvest on the commercial side to drive volume. Yeah, this year's a year of investment, but I think things can flip very quickly next year if things drop into place like we expect them to do. Okay, great. With that, we're almost out of time, so I'll go to our closing question. It's this is a loaded one: What's most misunderstood, you know, or underappreciated about Guardant? And you only have two minutes to answer. I think it's hard to answer that in two minutes. There are several. So I think on one side, like, I think on the core business, how much still on tap opportunities out there and the growth profile that we can have. I think on MRD, the reality of a segment of the market, the minimum is gonna be this, a segment of the market, tissue-informed MRD is not gonna be even an option. There's no tissue. You like it, you dislike it, there is no tissue, right? So for people who are even, like, five years out, you know, after their surgery, they're in a different pockets, you know. So I think the reality of Reveal is we are the only player on that side that can open up that market opportunity in a very meaningful way for the people who don't have tissue. You know, we can have a good competition with even tissue-informed assay. On Shield, oh, my God, this test can redefine cancer screening. The amount of life year gain, there is a big mismatch in the real world versus, I think, some investor sentiment. KOLs are excited about next week of what this can do, and we are gonna see it in terms of the pool of the market that we are gonna see after the launch, which we are seeing the evidence of it even with Shield LDT. We are very excited about the opportunity ahead of us. Okay. That's a great place to end it. Thanks so much. Thanks, everyone.