I don't know how this works. Okay. Thank you everybody for joining us. Today, we have Guardant Health, AmirAli, the co-CEO, and Mike Bell, the CFO. Guardant Health probably doesn't need too much of an introduction, so maybe let's just dive into a little bit more about some of your innovation here. Can you talk about smart liquid biopsy, AI, and the constant improvement of your assays that you're doing, you know, starting from Guardant360, you know, through the portfolio, the constant innovation and compound innovation, as we like to call it? Yeah, sure. Hello, everybody. Good to be here. So, you know, as the tagline of the company says, "Conquer cancer with data," we're a company that has been focused on capturing data, high quality data that would help with this mission of adding value in, helping cancer patients. It started with Guardant360 on the advanced cancer side, you know, running and generating data from over 500,000 samples and, you know, correlating a bunch of those kind of genomic findings with, clinical, medical records. When we look at actually fast-forward almost like, you know, 10 years post-commercialization of Guardant360, we are leveraging and we are benefiting from this treasure of the database that we have captured. This data not only help us to improve our technologies to find the genomic biomarkers better, but understand the biology of this disease better, that over time, help us to build products for earlier stage detection, especially the latest asset that we have around cancer screening, which Shield that benefit from all the insight that we gathered so far. Now, kind of double-clicking over some of these matters, Smart Liquid Biopsy is the new platform technology that has been rooted in this clinical insight and the data that we have captured over the years. It's mainly a new generation of epigenomic technologies that are getting added to the whole portfolio of the products that we have at Guardant. It would generate new insights, some therapeutically relevant information for managing cancer patients, all the way to cancer screening. It was incorporated into our Shield product first, this Smart Liquid Biopsy, and we are very close to actually incorporating that to Guardant Reveal. As we go to the next year, we are gonna incorporate that into Guardant360. So all of our products are gonna get upgraded with Smart Liquid Biopsy, which gives us higher performance, lower cost, and totally new insights that, for instance, Guardant360 or Reveal, the prior generations could not give to the physicians. Connecting that to the AI, you know, it's something that we have used in our, you know, our products, even, you know, some aspects of 360. It's not kind of new for us, but maybe something notable. We started adding AI into our digital pathology on the tissue front. That's around Guardant Galaxy. We incorporate that into Guardant Tissue Next product, that we are looking at PD-L1 with some AI kind of powered engine. And what we are finding is like, we find 20% more PD-L1 expression in some of the low expressors, which generate actually a bunch of excitement for us and our physicians. Good. Great answer. So let's just dive into a little on ESR1. You know, I think this is something you can only find in liquid. You got the benefit here in the first half, and then you noted a backlog that you got captured in the first half. Can you help us understand why would there be a backlog on this? What advantage do you have in ESR1 capture, and kinda how big this market could be? So ESR1 mutation actually has generated a transformation in metastatic breast cancer management. It's a mutation that happens. It could happen in ER-positive, HER2-negative breast cancer patients, majority of breast cancer cases, 70%-80% of the cases are ER-positive, HER2-negative. And it's something that mainly it's emerging mutation, and it means, like, you don't find it typically in the primary tumor. It gets evolved as a result of some of the therapeutic pressure, and it's very actionable now. And because metastatic breast cancer patients survive long based on all the advancements that have been made in the field, all these patients were eligible for getting tested with ESR1 once the drug got approved with the companion diagnostic of Guardant360. So very quickly, once that approval came earlier this year, we saw a huge jump in utilizations of our tests as companion to that, therapeutic intervention, and we saw a huge jump in utilization of Guardant360 in breast cancer site. So that generates a bolus of kind of sample processing for us in the first half and generates a huge growth year-over-year, and that huge growth of year-over-year continued for us. And, we are... Like, our breast cancer use case is at a new baseline as we speak now, and it's gonna continue to grow from this baseline that we have. Good. Thank you. What's the latest timelines on Shield? When is approval expected? I know you said 2024. Is there any... I think you said in the middle of the year. In previous cases, how long do you expect to go to market? How long do you expect for CMS coverage, and when do you expect the readout on, on Shield 2.0? Yeah. So we submitted our pre-market approval application to the agency in March of this year. And once we submitted that PMA, we said that we expect to get approval sometime in 2024. And since then, we are making steady progress with the agency. It's been very collaborative and collaborative, and a collegial kind of review process for us. We are making good progress, and our team has good confidence that approval is gonna be sometime in 2024. In terms of the launch, we are getting ready to launch the IVD version of the Shield right after approval. But the test is already in market as a lab-developed test with a small commercial channel that we had. There are over 1,000+ accounts that have been using Shield as, you know, early experience kind of setting for them. But we are gearing up to launch this test now post-FDA approval, and as we speak, we just started the commercial expansion on that, on that team. So we are excited about what could happen in 2024. Gotcha. What is an ADLT, and how do you expect to use it for your pricing advantages? So once we get FDA approval for Shield, there is National Coverage Determination already in place for blood-based colorectal cancer screening, that as long as the test meets some specific performance criteria and FDA-approved, it's gonna benefit from that National Coverage Determination. Our pivotal trial showed that the performance of Shield is well above that minimum bar, and once we get FDA approval, effectively, we are gonna get Medicare coverage. Now, connecting that to ADLT process. ADLT stands for Advanced Diagnostics Lab Test. It's a favorable pathway to incentivize manufacturers to do innovation and come up with innovative technologies that can add value on the diagnostic side. Once we are FDA-approved, we can apply for that ADLT status, and FDA-approved tests would qualify for that status, and that would enable a favorable pathway for pricing for Medicare, which is gonna be in place for some time. It's kind of a mechanical process that after FDA approval, we have to go through, and we expect that ADLT pricing to be in place for us in early 2025. Gotcha. If there's any questions, I'm gonna move on to the MRD portion of the portfolio, if anyone has any Shield questions? Okay. So right now, you know, there's a, it's clear that tumor-independent, or if you'd like to call it tumor-naive, I don't know which definition you like to call it, has advantages, particularly in convenience. Sometimes when you talk to oncologists, though, they tend to find that tumor-informed tends to be a lot more intuitive, i.e., there's tissue, we understand tissue, that kind of thing. Is there an analog that can be made for maybe, you know, tissue-based CGP and eventual acceptance of liquid biopsy? If you think about from the psychology of the oncologist. There are some similarities. You know, the standard of care before liquid CGP was even in existence was just tissue CGP, and it was more straightforward. You know, tissue testing has been around even for single gene testing, and, you have a sample, let's profile it, let's do the treatment management based on that. During those early days, even CGP through liquid looked like a sci-fi and wishful thinking till some of the technological advancement has been made, and then the clinical data supported that. In fact, you can get high accuracy information. In the MRD front, I think it's even more interesting because not only blood-based MRD tests, like tissue-naive blood tests, not only can do what tissue-informed can do, but also it can provide some additional information and insight that is not in existence in tissue testing. I give you an example. Let's say a patient with colorectal cancer goes for surgery, and you wanna do MRD testing in that patient. Tissue-informed MRD test would tell you if this patient still has residual disease or not, right? Blood test, not only it has convenience factor, but based on the technologies that we use, not only would tell the patient is MRD positive or not, but can potentially say where that residual disease is. And this has therapeutic impact, like a colon cancer patient who have residual disease still in colon or has now residual disease in a distant tissue like, liver. The intervention would be different. Some of these over time need to play out in terms of validation and in terms of showing that once you're using this information therapeutically, you can add value, but the science is there and the vision is there, and this is unique opportunities, I think, for blood-based MRD testing versus just blood-based CGP, which the main goal was try to get as similar information as tissue CGP, but just through simple blood testing. Gotcha. If we look through the years, let's say, you know, five years from now, 10 years from now, what do you think the split will be in terms of tumor-informed versus tumor-agnostic or tumor-naive? Obviously, I'm biased, but, you know, frankly, it's hard to predict what exactly we are gonna be five years from today. But when you look at which modality has the best product-market fit, we don't have any concern that the convenience factor of blood-based testing, the turnaround time of blood-based testing, additional insight that only exists in blood, not tissue-informed-based testing, would really make blood-based and tissue-naive testing the way to go. But, you know, validation studies need to be performed, utility studies need to be shown. Some of the intervention based on these blood findings needs to be proven. So some activities needs to be done, but we believe in this vision, and we believe the future would be very bright for blood-based MRD testing. All right. All right, so Mike, sorry, we've been ignoring you the whole time. So, let's just maybe talk about some of the OpEx. Yeah. Where's the profiling right now in terms of cash flow breakeven? What's the OpEx right now, in terms of screening? Yeah, I mean, cash flow breakeven, we sort of, we laid that out at our recent investor day. You know, we've, we're focused on reducing our cash burn every year. This year, we've been successful, or we will be successful in reducing the cash burn to around $350 million, and I think we expect each year from now to reduce that cash burn, and by 2028, be cash flow breakeven. So... And we assume then, you know, at a revenue run rate of around $2 billion. And yeah, and as, and as part of that is managing our OpEx. And, again, this year, we set the target of reducing our OpEx in 2023 versus 2022. Mm-hmm. We're gonna be successful in doing that, so we're on track to do that. Still, while we're reducing OpEx this year, you know, driving revenue growth over 20%. I think as we look maybe to next year, you know, I think OpEx overall is probably gonna grow similar to an inflationary rate. But there's gonna be some puts and takes. I think, you know, we'd expect research and development costs to come down. We've incurred, you know, significant costs over the last two years with ECLIPSE. That's now completed enrollment, you know, we continued that through this year. So that would drop off. So I think, you know, we should see a small reduction in R&D expense next year. We'd expect G&A to be relatively flat next year. Our biggest investment next year, of course, is gonna be on the sales and marketing line. You know, we're gonna be in a launch year for Shield, and we want to build up the commercial infrastructure there. So I think we can do that, but still manage our OpEx growth again to be sort of at an inflationary sort of level next year. Gotcha. And let's talk about the puts and takes in on gross margins, outside of screening. As we look into 2024 and beyond, maybe talk about the potential royalty headwind. Is there maybe some offsets in terms of favorable pricing in Guardant360 and Reveal that maybe still have the potential to come around? Yeah, I mean, I think, I think if you look at gross margins, it's better to look at it product by product. Mm-hmm. You know, I mean, starting with Guardant360, that's got very healthy gross margins. We just got confirmed just last week or the week before, the crosswalk of the Guardant360 LDT to $5,000. So that has been finalized, and that'll kick in from the first of January. So that's a positive for us, and that will push our Guardant360 overall ASP on the clinical side to $2,850-$2,900. So a nice upside for us there. And if you look at our gross margins on Guardant360, on the clinical side, those gross margins are in the high 60%. And on the biopharma side, where we're again, we're seeing improved ASPs through Guardant Infinity, then gross margins are in the sort of mid 70%. So Guardant360 has very healthy gross margins, and even if there's, you know, some royalties coming down the line, on that, I think we can still manage the gross margins to a very, very healthy level. TissueNext and Reveal, and the mix between them, you know, we try to manage that, so we get an overall gross margin of 60% for the company. I think TissueNext, we're making good progress on ASPs. We've got Medicare coverage. We're at 200 million covered lives now, but there's room for the ASP to increase, and there's room for our cost per test to decrease as the volume grows. So I think that, at the moment, is lower than 60%, but it can definitely improve over time. Reveal, you know, at the moment, it's gross margin negative, and the two key focus areas for us there, obviously, is ASP, getting reimbursement. We've talked a lot about our focuses on data development and hopefully getting CRC surveillance reimbursement and breast reimbursement from Medicare. At some point in the near future, that's gonna help gross margins there, and then with smart liquid biopsy and moving to an epigenomics platform, we can really drive the cost down on Reveal. So, you know, we wanna improve the ASPs and have a low-cost Reveal. Mm-hmm. I think overall, we try to manage the gross margins to be at least 60%, but I think as we go, and if we can hit all of our initiatives, we can have gross margins trending towards 70% over the next few years. Gotcha. Well, so if we look at—go back to the core growth of the business, I mean, I think that the new products have definitely helped drive growth, you know, Reveal, TissueNext, Response, etc. You know, in the coming years, I mean, should we think about this as continued innovation, even in continued new products, in the profiling business, in the monitoring business, to help drive that growth? And what do those products look like? You know, I think intuitively, you know, adding tissue, adding Response, adding MRD is all very intuitive and kind of offered by a lot of companies. I mean, is there—What’s the room for innovation here to be added to that portfolio? I think still the opportunity is huge in terms of what we are seeing, what we can do with our products across the continuum of care. There is a lot of trap value that we can unlock. But it's not just Guardant innovation that would drive this, you know, additional opportunities for us. I, I go back again to ESR1 approval. That's not gonna be the last CDx approval for metastatic, you know, cancer patients. In fact, there are pipeline of other activities, some that we are working with pharma companies, some that pharma companies are working with others or independently themselves. Any kind of new approvals have opportunities for us to kind of drive the demand and growth. When we think about internationalization of our offerings, like, we are very excited about what we can do in Japan with our Guardant360 franchise, right? It's not just innovation that would drive those kind of growth opportunity for us, but just a bunch of approvals and globalization that can drive those growth for us, too. Yeah. I think in CGP, you know, we see a lot of different companies with pretty decent market share. When we look at liquid-based CGP, we don't really find that much competitors. I mean, who do you see in the marketplace? And I mean, do you expect to see others, and why do you think it's been maybe slower to seeing competitive responses in liquid than, I don't know, maybe we would have guessed two years ago? You know, we consistently talk about there are multiple barriers to really get to this market, you know. First is technology, like, on tissue side, like, there are a lot of mom-and-pop shops that could just start a tiny lab and be able to sequence FFPE samples, right? Liquid is not that easy. Second is operation, lab operation. Now, on average, we have five-day turnaround time for our Guardant360 CDx. This is not easy, and this is the way market is shaped when about 20% of advanced cancer patients are getting tested with 360 with this level of experience. Do you think easily somebody can just bring a test up, and then what happens? Typically, like, there are some companies that they tried it, they launched it, and they had three weeks turnaround time. What do you think the adoption would be? They were in the market, and they left the market, right? So, when you think about the clinical evidence that has been generated for Guardant360, this is not commodity testing, that as long as you can just do liquid CGP means clinical performance and clinical utilities inherited. No. You know, all those kind of validation, publication, experiences that we have developed across, you know, globe are kind of adding to this barrier. Reimbursement. When more than 300 million people have access to Guardant360, like a company that wanna go through a lot of billing or huge amount of investments to go and enable the access till they can enable that 300 million kind of reimbursement, these are not straightforward. As a result, yeah, some companies came and, gone out of this market. There are still, like... It used to be competitive landscape, and it continues to be competitive, competitive landscape, but we feel very good in the market position that we have on the liquid side. I think one of the unanswered questions that I think a lot of investors are looking at is post-pandemic screening backlog. And what I mean by that is, you know, during the pandemic, we didn't see as many, say, colonoscopies as we saw before, and then coming out, you see 2022, 2023, you know, maybe they're running to Cologuard, maybe they're running to colonoscopies, and suddenly you see a lot of cancer patients. And, you know, has this helped Reveal? Has this helped Guardant360? Has this, you know... So any thoughts to whether or not we've seen a pull forward or even, you know, adding in the 45 - 50 age population to the screening, has that had any impact on finding more late-stage cancer or even mid-stage cancer that would be applicable to MRD? So we looked at it to some extent, and we don't believe that was a major material growth driver for us. And the reason is, for metastatic breast cancer patient, the survival is so short that, you know, the delayed screening is not, you know, if a person is gonna have advanced cancer, unfortunately, like within 12-18 months, the journey would be over for a bunch of kind of indications. And that kind of a lag of pandemic did not generate a significant amount of bolus of new testing that needed to happen, unlike the screenings. Like, you know, it was very dominant in terms of screening. But we are gonna continue to monitor the field, I think, especially for CRC, as more patients are gonna get diagnosed pre-symptomatically. That could have some kind of influence down the road for MRD testing when there are more pre-symptomatic patients that go through surgery. So, but I think when we look at our growth trajectory, I don't think those would be any kind of dominant major kind of drivers for us. Gotcha. We have 20 seconds. So, just as we look back, it's 10 years from now, it's 2023, you're at the Piper Conference, what are you most proud of, that you've accomplished in these last 10 years? Frankly, a lot of patient impacts that we have and, you know, contribution to the cancer field. Now, liquid testing is standard of care, and it was just a wishful thinking 10 years ago. I think we delivered on a bunch of promises during our IPO roadshow, and we look at our summer investor day as our second IPO promise to the field in terms of what we are gonna deliver for the next five years, and we are very excited about what we can do.