Guardant Health, Inc. Aktie

I think we can get started. Kallum Titchmarsh here from the Life Sciences team at Morgan Stanley. Welcome to Day 2 of the Morgan Stanley Healthcare Conference. Really pleased today to be joined by the team at Guardant Health. We have AmirAli Talasaz, Co-CEO; and Mike Bell, CFO. Thank you both for being here.

Thanks for having us.

Before we get started, just for disclosure relating to this discussion, please see morganstanley.com/researchdisclosures. So a lot to discuss. We've had quite a bit of recent news since those Q2 results, but maybe we can just rehash that Q2, very strong performance across the board. Would love a little state of the union on Guardant Health to kick off, and then we can go into some specifics from there.

Yes, sure. So great to see you guys. Q2 was another fantastic quarter for Guardant Health. The flywheel of Guardant is moving, accelerating and a bunch of stuff that we worked on for a few years, they are all coming to result and contribution for Guardant right now. So overall, we reported more than -- greater than 40% revenue growth year-over-year.

On the oncology side, volume growth of over 60% on Shield front, volume -- the growth of more than 250%. And we reached to a point that we are not building CRC screening market with Shield anymore. That category is already out there. We are at the phase of category scaling and developing that market as fast as possible.

On oncology side, the Smart Liquid Biopsy and Smart platform in general, both on liquid and tissue front is resonating very well. It's helping to develop the market and help us with a bunch of market share gain through a bunch of applications that it has enabled -- it's enabling for the oncologists to provide some additional actionable clinical information. So we are very excited of what we reported.

And Mike, any standouts from you for the quarter?

I think we just talked about all of the great news on the volume growth, on the revenue growth year-over-year. So no, it was just another very, very strong quarter from Guardant. And yes, we're really pleased with Q2.

Amazing. So let's maybe dive a little deeper into the oncology business first. You have an increasingly well-established product, both in liquid and in tissue. How do you see the G360 Liquid and Tissue working together rather than competing modalities just to make Guardant the kind of top choice for oncology practices?

So they are really at large scale, complementary to each other. If you look at actually the guidelines now for a bunch of cancer types, dual testing with both liquid and tissue is indicated and recommended in those guidelines. And what actually the recent FDA approval of Guardant360 Liquid CDx provide us is really simplification of that ordering workflow and making sure that both Tissue, Guardant360 and our Liquid360 are orderable and accessible for physicians and they're reimbursable for us.

The data that's coming out is also supporting this kind of dual use cases. So it's more than really competing kind of position. It's complementing on the data front, also having both of these 2 assets really helping us to really enrich the data platform that we have at Guardant. When we are looking at -- we're literally the only company on the CGP front that is providing epigenomic information and capturing that data at scale. There is a lot of apps that we have developed so far and many apps that we have in pipeline enabled with the power of the data that we are capturing.

I think it's just helpful given the growth rates you're pulling out to just level set on penetration today across your liquid and tissue categories, not just in the core indications, but also maybe more broadly into some of the new indications you've been looking into as well.

And it's a function of like different cancer types. But in general, tissue is well penetrated, about 70%, 80% of the market developed. So really what Tissue 360 with the innovative platform that it has enabling us to do is really the market share gain relative to the competition by providing additional insight to the clinicians. Liquid biopsy is still pretty underpenetrated. When we are thinking about maybe overall, and again, cancer by cancer is different, maybe we have like about 40% plus/minus kind of market penetration at this time. For a single time point use case for liquid, there's still a lot of room to grow.

On single time point and then the other dimension of really going towards longitudinal monitoring and providing multiple testing per patients. Right now, still, we are doing 1.2, 1.3 tests per patient in terms of liquid and tissue testing, and that number can grow in a meaningful way. We are also very excited with the recent FDA approval, which really was landmark for liquid biopsy field and especially for Guardant360 platform to enable longitudinal monitoring of the patients. It's a totally new use case for liquid biopsy testing.

And we get pretty positive feedback just on that genomic plus epigenomic inflow that you create with the CDx platform. What do you think physicians can do today with that product that they perhaps couldn't do a few years back? Maybe just give some use cases from your experiences.

Yes. So on the genomic side, it's kind of pretty straightforward. Now it has over 700 genes. The CDx versus the prior one was about 10x smaller. And epigenomic is really where the main differentiation is. I'll give you maybe an example of an application. So a lung cancer patient who has been diagnosed with non-small cell lung cancer. It's some kind of specific pathway for treatment and management of that disease. We know that some of these patients go from non-small cell cancer type to small cell lung cancer type. And a large scale, this information is hidden to the physician because in order to get to that information, you need to do rebiopsy of the tissue of the lung, which is not really very typically done.

And the treatment paradigm of small cell lung cancer is totally different. Now with this Guardant360 Liquid through epigenomic data that we have and the application that we enable, the doctor can look at this transition very easily. Another kind of story that, in fact, in this group, I just heard is some of the patients who have occult cancers through epigenomics, we can figure out where is the site of the tumor.

And sometimes actually for this specific patient that I heard is like it was not an occult cancer patient, but really the oncologists were concerned if the diagnosis was accurate or not. And Guardant360 Liquid, in fact, showed that what was considered breast cancer patient was, in fact, had a totally different cancer type and the treatment of that patient got changed in a very meaningful way.

And Mike, just on the ASP going up to the ADLT price, I think, just under $8,500. Maybe just talk to us around your confidence in that pricing outcome and just the math we should be doing on that conversion over from the current price to the ADLT price?

Yes. We're very confident with the ADLT process. We've gone through this twice before now, first of all, with the old Guardant360 CDx back in 2021 and 2 years ago with Shield. Both of those have gone through the ADLT status after receiving FDA approval and Medicare coverage.

And so it's a relatively straightforward process. If you're FDA-approved and Medicare-covered, then you qualify for ADLT status. So this is the same now for Guardant360 Liquid CDx. We're in the process in the ADLT process. So we expect that to come in the first half of next year. So very confident on that.

And obviously, once we get that, you mentioned that ADLT price will be $8,455, so an increase from $5,000. Then over time, we would expect an increase in the overall ASP for Guardant360. It's around $3,000 now compared to a Medicare rate of $5,000. So something like 60% realization of the Medicare price overall when you include all the Medicare Advantage and the commercial payers and the Medicaid and some of the 0s.

So it's -- I think it's reasonable to assume that over time, and we think this will take sort of 18 to 24 months for all of the payers to sort of change their prices. But it's reasonable to assume we'll sort of realize something like 60% of $8,455 which is around $5,000. So I think we look at that in 2028 as being sort of our target ASP for Guardant360.

Great. And one of the newer updates since Q2 results are SERENA-6, camizestrant as well approval there and then SERENA-4, not working out as the trial had planned. So talk to us about what that means for Guardant specifically and the use cases there because I think it could unlock this new meaningful opportunity for the test.

It's very exciting. Like it's the first FDA approval in an indication of longitudinal testing using Guardant360 in general liquid biopsy. It's a new clinical paradigm, and that's why even I think contributing the fact that FDA went through a AdCom process for this drug. And now it's proven actually after 3 failures, not just by AstraZeneca, but by other oral SERDs that using that drug as a frontline, first line is not going to work.

So you really need this biomarker stratification, monitoring this emergence of ESR1 mutation to use this drug on the right subset of patient population. So this really emphasized the value of liquid biopsy and Guardant360 is the only FDA-approved CDx.

Now in terms of the size of the opportunity, we estimate about 37,000 breast cancer patients to fall under the indication use of this drug. In the trial, those patients needed to get tested every 3 months. So it's about maybe 150,000 annual testing opportunity. But obviously, we have work in front of us.

We need to see how the drug launch goes by our partners in AstraZeneca in terms of the adoption. And in order to fully realize that opportunity, we have some work to do on the reimbursement front on changing the 90.2 NCD, which right now doesn't allow Medicare payment for longitudinal testing, but that conversation has been ongoing, and we are working on it with CMS.

Any rough time lines you would put on that?

Probably maybe we are 1 year away from that.

Okay. Helpful. And then Reveal as well, I think was a standout for the second quarter, some really strong sequential volumes there. Could you maybe just unpack where that success is coming from, whether they are existing MRD users that have switched over to Reveal or whether these are new MRD users coming to the table? Maybe just a little bit of color on that success would be really helpful.

So the Reveal MRD was getting used by a fraction of the oncology base that we have in terms of ordering physicians. And what this Reveal treatment monitoring is enabling, it went actually much better than what we expected. We just like finished the second full quarter of the launch with that product now.

And effectively, all Guardant360 user base, which is vast, vast majority of the oncologists, when they are considering CGP for profiling, now they have an option to bundle a treatment monitoring post 360 if they are interested.

It has a very nice synergy, same call point, similar same kind of channel that we have. And we have some work to do on the reimbursement front. We have some kind of applications in front of MolDX, like 2 major indications of chemo and IO. But the adoption has been very great, which is really an endorsement of the brand value that Guardant360 has in front of oncologists and to some extent, even Reveal franchise.

And then I guess, with Reveal Ultra coming by the end of the year, I believe. Just how are you thinking about that kind of tumor-informed versus tumor-naive trade-off in MRD? And I guess, what is your expectation longer term of the relative adoption of both products?

So we wanted to make sure our bag is complete. There are some doctors that really they prefer tumor-informed MRD versus tumor-naive MRD. So we are leading the tumor-naive side, but that was a gap that we had in our pipeline and our backup commercial team. And now we are going to have it by end of the year.

Unlike many players in the field of TI-MRD that's kind of their platform or their offering is kind of at least on the technology side, looks kind of me too. Reveal Ultra is pretty differentiated. We are very excited to talk about it when we release the product. We are on track to launch it before end of the year.

I think it's going to be a fantastic contributor to the whole field of MRD and Guardant oncology brands that we have. In terms of use cases, like it's not a replacement of Reveal. It's really for some doctors, for some patients, they prefer tumor-informed when the tumor is an option. And for some patients, the convenience or the faster turnaround time or lack of tissue really provides a better fit for just liquid-only Reveal to be used. So I think it's just going to give optionalities to the oncologists.

You said it's just some internal validation work that's holding back the Ultra launch. That's the only remaining step, right?

We are almost done. Stay tuned. It's going to come out before end of the year.

Amazing. And just given your scale, I think, increasing in MRD, having that very established CGP franchise, how does that kind of full suite solution resonate with the physician versus incumbents that perhaps are under-indexed to one of those product types?

Yes. I think like Guardant is not like a holding company of a few business units, frankly. All these assets that we have are really working together and give us leverage and new commercial opportunities. I think on Reveal and 360 are very clear, like we talked about 360 connecting it with Reveal for treatment monitoring.

And then when the treatment is not working, again, the profiling is going to be indicated for another Guardant360, even in the MRD in early stage, monitoring those patients with Reveal and at the time that Reveal is finding something, then typically, those patients needs to go through profiling and reflex to Guardant360 would be indicated in those patients.

There are some subset of the market that they really value single-stop shop or the convenience of the ordering. Now these kind of portfolios that we have give a lot of ease and connectivity of offering and the data for easy oncologists in the marketplace. Even on the Shield front, what we are seeing is even connecting Shield to our oncology brands on both sides are giving some commercial benefit.

So just imagine down the road when a good fraction of CRC patients are going to get initially diagnosed through screening done through Shield. Right now, when we are talking with some accounts, they are interested to know that we have some screening solutions in terms of a complete portfolio. Nobody else, Guardant is the only company who has offerings across screening, MRD and CGP testing right now.

On the other side, on Shield front, we are getting the benefit from established brand of liquid biopsy pioneers and trusted vendor when we are talking to primary care physicians. That's been helping. Amazing to see this market adoption that we are experiencing.

That's a good segue probably on to Shield. I would say another couple of very good updates there. On the commercial side, since those second quarter results, we had Carelon and then Epicor. So just unpack a little what that means for the Shield commercial program and like maybe some numbers as well on just the covered lives now and then how rapidly you can go after that opportunity.

Yes. I think the flywheel of Shield is moving very fast. Like literally, it was about a year ago that I think the conversation was, would the patient and physician use a blood-based colorectal cancer screening. Does this category even exist? Do unscreened patients get tested with the blood test? Now just in a short time of about a year, we are in a category scaling phase.

About 80% of all eligible patients have coverage for Shield. 94 million people with multiple success that we had and wins that we had during the last few months, few weeks, now 80% of people have coverage for Shield, dramatically changed. It just gives us opportunity to provide more equitable access to this test and continue to drive commercialization and scale-up of this brand.

And is there anything holding back the momentum that you can go forward, just given the commercial coverage is there now, will be coming and evolving. But is there anything that's holding back the rate of uptake that you could perhaps push out into the market? Or do you feel like you have the capability, supply chain infrastructure to service that demand?

We are moving as fast as Guardant is a fast-moving company. And for sure, we are doing as fast as we can in terms of scale up, like dramatically, the size of sales team has increased like we mentioned that we started this year with more than 300 people in the field in terms of commercial field force in Q2 earnings, we said at that time, we had more than 400 people in the field. Our DTC campaigns went from nothing last year to some pilot phase earlier this year and now really at a very scaled DTC campaigns right now.

In terms of lab, we bring forward some of the capacity that we are planning to build down the road. We moved it forward. So we are very excited with those kind of progress that we are seeing. On the workflow, we got FDA approval for a more scalable workflow for Shield very recently. So that would help with the scale-up and also reducing the COGS of Shield in a meaningful way, even before end of the year. So in general, we're moving as fast as possible.

Mike, maybe hit on that COGS reduction for Shield. I think it was a pretty interesting evolution that we've seen.

Yes. We know we had a very nice reduction in cost per test recently. I think we've been mentioning for a long time that really we've got 3 main drivers of cost reduction over the next couple of years to get us from over $1,000 per test when we launched, and we're targeting a $200 test when we're at scale. And so we've made really good progress scaling our lab, getting a lot of efficiencies.

Volume, of course, has been a driver to date of bringing the cost per test down. And in Q2, it was just over $400 per test. But recently, we got an FDA approval for changes to the workflow. So we've taken out a lot of analysis that was unnecessary. That needed to go through an FDA's PMA process just to prove equivalency with the original test, but we were very successful in doing that.

So that's now gone live in the lab. And we expect that by the end of the year, we'll realize something like a 15% reduction on that $400 COGS that we had in Q2. So we think we'll exit the year with a cost per test of $350. We've still got work to do. We've been investing heavily in automation. Our plan is to take out as much labor cost as possible in the lab where we're processing Shield.

So that work is ongoing. That will again need to go through an FDA approval process. But when we come out of that, and we expect sometime probably late '27, we'll see another significant step down in cost per test and then continuing to drive efficiencies with additional volume, that's going to get us to $200. So I think we're well on the way with the target that we set, and we're really pleased with the results.

And with these new commercial wins, could you maybe just unpack what that means for ASPs and what those different rates look like perhaps across different plans?

Yes. Obviously, it's getting coverage on the commercial side is very positive, and it's going to have an improvement on what we get paid by the commercial payers. Just as a reminder, we've got the Medicare ADLT rate $895. That's been in place now for 2 years, and that's a well-established rate. And over the last 2 years, we've seen very strong payment from Medicare Advantage payers.

And so we're getting very good reimbursement on that side. Where we've lacked to date has been on the commercial side. And with no coverage, we've effectively been getting 0 paid. So we've been managing our ASP. We've primarily been focused on the over-65s where we do get paid. As we've got into guidelines with ACS and now with these commercial coverage decisions, we'll start to open up to more and more under-65s.

So that will have 2 impacts in the near term. Obviously, for the payers where we're covered, we'll start to get paid. We'll have to see what that is, and we'll have to see what decisions we want to make about contracting with those payers. But those 0s will start to transform into paid tests.

But we'll still have some 0s from all of the other commercial payers. So I think with our ASP, it's going to depend a lot on the mix over the next couple of years. We know that, that percentage of commercials and potentially the percentage of 0s in the short term is going to increase.

So we had, for the last couple of quarters, an ASP in the $800 range. We've guided for the remainder of the year at sort of $770. So a little bit of a dip. There might be a further dip as we have more and more 0s when we open a wider to commercial payers. But obviously, this flywheel that AmirAli mentioned on commercial reimbursement, that's going to drive ultimately the ASP back up. And so we're very confident that we'll have a strong ASP in the sort of in the medium to long term.

Great. And AmirAli, just on that -- the ramp, any seasonality we should be thinking about for the third quarter? I realize, again, it's still early on. And so that ramp probably still looks pretty aggressive, but anything you're seeing out there in the market?

So just as a commercial organization on PCP front, still, we don't have a lot of history data to really to rely on. But we have some, and we are looking at a lot of other kind of external data. Like in Q3, like what we talked about is there are some seasonality in patient foot traffic in PCP offices during the summer days in Q4, typically, like you see some kind of weather events. So these are like in terms of some of the dynamics of Q-over-Q, and we consider it when we set our guidance for second half of the year in our Q2 earnings call. So besides that, nothing else to call out.

And then maybe one for both of you. But just thinking about the level of investment going in behind Shield now, DTC spend and the reps, how should we be thinking about the direction of travel for both of those in the years ahead?

Yes. I mean we've -- I think we've consistently said that as Shield continues to progress and volumes increase and revenue increases, we'll be investing any incremental gross profit back into the sales and marketing line basically to drive the commercial scale up for screening as quickly as possible.

So we've been doing that. Obviously, getting commercial coverage, being able to reduce our COGS is going to just allow us to reinvest more gross profit back into the line. So I think over the short term, we should just expect that investment to continue to ramp. And we want to get to a place where we've got 600, 700 reps and a very strong DTC level of spend as soon as possible. And so yes, we're scaling this quickly. So you should expect that in the near term to continue.

Great. And then just on competition, obviously, an evolving market, more people coming into the fray. What do you think are the components of Shield that make it stand out as the preferred go-to screening test here? And how you think about that market evolution over time, what that rough share perhaps could look like 5 years from now?

Yes, I'm very confident about the position that we are in now. Still today, Shield has the best CRC detection readout of any other kind of technology out there. So we are still the best in terms of CRC detection. It's the most clinically validated test when you're thinking about the experience with way over 200,000 physician testing, real-world adherence, a bunch of randomized studies that we've done in different health systems or setting to show the overall rates of screening can go up significantly publications that we have behind Shield. In general, it's the most clinically validated platform.

We also have the network and infrastructure that we built at Guardant during last decade, I think some elements like looks kind of maybe simple, but in reality, it's a major infrastructure build-out that takes time, like, for instance, blood draw phlebotomy networks. Like at Guardant, now we are working with tens of thousands of contracted phlebotomists that help across our brands. And that's not easy to build in like a regional setting at a national scale.

So I don't think a bunch of this competition, which is going to come to the market have anything on that front. So -- and we are -- we have first-mover advantage with a commercial team, which is really focused on this blood-based CRC screening. I think some of the competition is going to have hard time with the positioning of maybe stool test versus blood-based test. And lastly, over time, this MCD opt-in is going to show a powerful contribution in the values that we are going to offer to the physician versus CRC-only assay.

Yes. Maybe we can hit on the MCD opt-in. We obviously have an AdCom for a competing MCD test next week. So how are you thinking about that category? What's the physician feedback been? I think you said the majority have opted in for the MCD feature. So maybe just talk through the evolution you're seeing there.

Yes. I think still, we are in relatively early innings of this MCD opt-in and offering in the marketplace and majority of physicians are using Shield now as multi-cancer detection test, the way that actually we built this platform.

We were not sure if like PCPs in general that sometimes you look at as maybe they are not the most sophisticated physicians out there, they would adopt this in such a fast space. And it's the broadest way of offering MCD in terms of accessibility. As long as the patient is indicated for colorectal cancer screening, which is 90% of the patient age 45 and above, if their doctor is interested and the patient is interested, they can opt in to receive multi-cancer detection.

That's very different than maybe some of the competition -- competitors offering that it's not broadly accessible for everybody. It requires very high out-of-pocket payments in order to get access to this kind of innovations, and we never believe that's the best way to really make sure the innovative test needs to get offered.

So we are very excited. And I think over time, we are going to continue to see that this was the best way to make MCED available in the marketplace. We wish our other players with their AdCom best of luck. It would be good for the field to move forward if that outcome goes well. But that would not give them really a broad reimbursement pathway versus the pathway that we have, which is very unique to us.

And anything from the data you're seeing on the MCD side thus far that surprised you or interested you?

Still it's early days. I think the adoption has been pretty good. We are happy with the rate of data that we get access to on the patient side in terms of patient authorization it's going pretty smoothly and continuing to trend in the right direction. In terms of performance and sensitivity, it's too early. We don't have data after we opened up this MCD opt-in to be more patients.

And a couple of minutes left. So maybe we can just quickly hit on biopharma. I think growth is shaping up relatively in line with expectations so far this year. But maybe just speak about the pipeline that's evolving with those biopharma relationships and any assumptions we should have multi kind of year horizon on that business?

Yes. No, biopharma continues to be a very strong engine for us. Not only on the -- with our pharma partnerships, but of course, it's a leading indicator on the clinical side. And again, all of the work that we did with AstraZeneca and SERENA-6 now comes through into our and to drive the clinical oncology business.

So it's a strong contributor to Guardant. I think you've seen over the last 12, 18 months, we've had multiple CDx approvals. We've announced multiple strategic partnerships with big pharma. So we're being more and more integrated into the whole clinical development process with them and Guardant360 is being a key element of that.

And so yes, I mean, we look at that to continue. We think those pharma partnerships are incredibly important for the whole of the business. And things are going well. On a long-term basis, we've guided for in 2028 for our biopharma business to be roughly $300 million, which infers a sort of roughly a 10% to 15% annual growth rate, which is roughly in line with the market. So we're very confident about that, yes. And hopefully, some of these strategic partnerships that we've signed can help us accelerate from that.

Amazing. Well, AmirAli, Mike, thank you so much.

Thank you. Thank you.

Welcome to the Canaccord Genuity Growth Conference. I'm Kyle Mikson. I cover Life Science Tools and Diagnostics for Canaccord. Really pleased to welcome you to a fireside chat with Guardant Health, here with us today. Company is a leader in precision oncology diagnostics across screening, MRD and therapy selection.

With us from the company, we have Helmy Eltoukhy, Co-CEO; and AmirAli Talasaz, Co-CEO. Thanks guys for joining us today. Appreciate it.

Thanks for having us.

Let's start with the 2Q ' 26 earnings recap. You guys had earnings recently. Again, like a really strong quarter, nice beat, raised guidance. Can you just walk through the results, puts and takes from the quarter?

Yes. It's -- once again, I think it shows a business that's really firing on all cylinders. We have these 3 overlapping S curves, very large market opportunities that are all growing very rapidly. We had great growth with Guardant360 in our oncology business. That's our flagship therapy selection test. We saw over 30% year-over-year growth there. We saw even greater growth for our tissue test. And it's really, I think, just the momentum we're seeing with the Smart platform, this really broad-based genomic -- epigenomic platform we launched almost 2 years ago now, and we're continuing to see sort of that pay dividends in terms of continued volume growth and adoption.

We're also seeing very good strength in our MRD business. This is the next market that we're in, the sort of $20 billion recurrence detection market. We have our product Reveal that has been doing really, really well. It's been growing over 100% year-over-year. We recently launched a new indication for therapy monitoring there in November of last year, and we see really good growth with that market really drafting behind 360 and the strength we have with oncologists.

And then finally, with Shield, we're seeing, I think, continued very strong momentum there, one of the, if not the, probably most successful launch in diagnostics from both a volume and revenue point of view. We're seeing, I think, 50% quarter-over-quarter growth there and multi-hundred percent year-over-year growth there. So I think a lot to like about how the year has progressed so far.

Perfect. And then just kind of diving into that, I believe oncology volumes grew like 60% year-over-year. Liquid, I believe, grew like 30% and Tissue was above that. And then Reveal, you just said that it was growing over 100%. So maybe just in Liquid, it's the historical kind of business. So some catalysts we'll talk about later.

But could you maybe just help, maybe size the tissue and the Reveal kind of like revenue or volume streams right now compared to what we've seen with others in the market, market share has talked about. Just how large -- how material is this in terms of moving the needle for you financially?

On the therapy, so actually on the Liquid and...

Reveal and G360 Tissue?

Yes. So those right now are obviously smaller contributors to the overall business compared with Guardant360, which we launched in 2014. But the fact that those are growing, I think, very rapidly bodes well for the coming years. We think tissue is going to be a pretty large segment for us as we continue to lean into it. What we're seeing is that, that flywheel just takes time to sort of gain speed, especially for a product like a tissue product that we have incumbents in there. There's, I think, legacy products that are out there.

But as physicians start using it, trialing it, sampling it and then they gain experience with our lower QNS rates, the comprehensiveness of the test, all the apps that we have on it, we're seeing that momentum build up, and it's something where I think we can continue to sort of take share and build that up into a fairly sizable business. MRD, obviously, I think, is still very much in its early innings. That's something where not only do we have, I think, the premier tissue-free MRD franchise right now. We're about to launch this year, our first tumor-informed offering, Reveal Ultra.

And so we will be probably the company with the most comprehensive offering in oncology in terms of liquid tissue, tumor-informed, tissue free. And we think that will also carry a lot of momentum on its own in terms of -- especially at the key account level in terms of large cancer centers sort of using our portfolio for the bulk of their patients.

Perfect. One more on the kind of the quarter and what's currently happening. So on Therapy Selection Liquid, you're growing as fast as some of the competitors, the 30% or so. How are you able to do that with such a larger like revenue and volume base than these other companies?

Well, I think it goes down to architecture of the technology. It's just head and shoulders above what we see out there. It's the only liquid product that has full comprehensive genomics and epigenomics in terms of methylation. There's now hundreds of thousands of samples that we've used to train these applications that we've launched on that platform. It's allowed us to do things that essentially, I think we were once considered science fiction in terms of being able to tell the histology of disease, seeing transitions from non-small cell lung cancer to small cell lung cancer in blood. We have FDA approval now in that platform. So we have just, I think, created both a platform and a moat, frankly, that I think has put us in a really good position.

And then the other piece is it takes time with diagnostics to essentially have physicians understand the power of the platform, especially with all of these apps and with all of these features. It's not like you can order just one test and immediately experience all the wonder that is Guardant360 Liquid. You have to see it, interact with a particular patient subset that has that mutation or has that sort of feature or that biomarker.

And as physicians have continued to use the test, I think they're gaining more and more confidence that this is something that is truly differentiated, which is why we're seeing that acceleration and the momentum.

Yes, impressive part. AmirAli, on Shield, it's been very impressive ramp so far. It's been a beat and raise every quarter that you've offered. And I think in terms of the guidance for revenue volume, it's been well over a year, obviously. What surprised you most about the launch and the adoption so far? It's obviously been very positive and there's been catalysts, but what in your mind kind of stands out?

Yes, we are very excited with what's happening on the Shield front, like we're in the second year of launch now, and it's really -- I think we graduated from category building phase to really category scaling right now.

The amount of market adoption of Shield is obviously way more than what we thought, how fast HCPs and PCPs are using this test on how many patients using -- they're using this test. The productivity of our reps is way more than what we expected from them. And frankly, most recent development with UnitedHealth Group was fascinating. We didn't expect a major payer, which is typically a laggard in giving coverage to innovative technologies to act first and provide very broad access to Shield testing for -- to all patients within their plan. So in this world of managed care, we believe no payer want to be first, no payer want to be last. And definitely, this kind of development is very exciting for us.

Yes. So on UnitedHealth, I mean, again, very surprising that, that occurred. Maybe talk about -- I mean, how that came about at all? And also why we shouldn't expect other large commercial plans to join suit over the next year or 2?

We didn't expect it. Having said that, we are working on it for multiple years. Because of our oncology products, we had multiyear relationship with UnitedHealth Group. We've done pilot of Shield within some of the employer base that United was managing their health benefit and the experience there was also very positive.

So after this multiyear conversation and recent guideline inclusion and lastly, the guideline inclusion by American Cancer Society, that really acted as a closure and the final triggering point for them to give us positive coverage for Shield blood test.

In terms of other payers, we don't expect any major payers to give us coverage before end of the year. Having said that, we are having some positive and constructive conversations with several players in the field, and we see what happens.

And I guess on the ACS guideline front, what's that tailwind sort of look like for you in terms of the 12 states or so that would cover?

So we knew that American Cancer Society guideline is well respected in the field. We knew about some state-level mandates that once American Cancer Society recommends a colon cancer screening test, there would be state-level mandates for coverage of that test. What we did not expect is the impact of American Cancer Society guideline in decisions by major payers, including UnitedHealth Group. So that was unexpected, and it's a very good and positive surprise for us.

Okay. And then the Shield, the new approved workflows that are lower COGS, I believe. I mean what's -- in addition to that type of an improvement, what can you do on the performance side over the next few years? And what's -- just like give us a flavor for like what you're kind of cooking up behind the scenes for Shield?

So we are in still very early innings of commercialization and scaling within this category of CRC screening. Having said that, the gross margin of Shield is pretty healthy as we speak today. So when you're thinking about the Q2 ASP that we reported, the COGS of $400 -- roughly $400 that we reported in Q2, we're already sitting on a pretty good gross margin there.

Having said that, we have a road map to reduce our COGS for Shield and improve the scalability of that test within the next 2 years. We got FDA approval for newly enhanced Shield workflow, which increases the throughput of the Shield and also increases the efficiencies and reduce the cost for us. That should reduce the COGS of Shield by 15% by end of the year.

And we expect and continue to be on track that sometime in 2028 at scale, the Shield COGS would drop to about $200. So ASP of north of $700 in 2028 and COGS profile of approximately $200 would generate a lot of exciting gross margin profile for us.

All right. Just maybe just taking a step adjacent to this for a second on Shield. So a competitor today had a breakthrough device designation announced for lung. You guys have the lung kind of indication in the works and the study and so forth. Maybe talk about why you guys have this moat and advantage in screening, whether it's for single cancer or multiple cancers.

I believe we got our breakthrough device designation for Shield as a panel of 10 cancers where lung is part of that 10 probably like 2 years ago. So I think other competitors in the field are continuing to play some catch-up games with us.

And this first-mover advantage, which kind of rooted in working on Shield during the time that there were not many believers this thing would work is generating a lot of opportunity for us. So Shield as a platform, we developed it as a multi-cancer detection platform. It's clinically validated for a panel of 10 cancer types right now, all solid tumors.

And for one indication, colorectal cancer screening, it's FDA approved. We are also working on FDA approval for lung cancer screening. That's a lung trial that we are doing during the last 4 years. We made very good progress. We finished enrollment. All the patients are -- have finished their clinical follow-up or going through the clinical follow-up, and we continue to expect to finish the follow-up and clinical database lock probably sometime before end of the year or early next year.

All right. Excellent. And then on the MCD component, the opt-in. So you've been kind of offering that for some time now, maybe almost 1.5 years. I think the attach rate is pretty strong is what you've said recently. So maybe remind us what you're going to use that data for and how that compared -- like where does this kind of fall on the like the Vanguard study, for example? And what's the go forward over time with MCED?

So right now, when the patients are going through CRC screening and they are eligible for CRC screening, patient has a choice. If they are interested, they can opt in and receive the information about 9 other cancer types as long as the patient participate in our data initiative program that we have effective they authorize us so that we can get access to their medical record and we can monitor really the performance of our MCD test.

Shortly after launch, we were amazed with the adoption of that opt-in by physicians. And we reported in our Q2 earnings call that now a majority of PCPs who are prescribing Shield are, in fact, opting in to receive that multi-cancer detection results report. So what that gives us the opportunity is to build this U.S. patient database of the performance and utility of MCED testing very quickly, powered by the commercial leverage that we have and scale-up of CRC screening and the strong opt-in by physicians and the patients that we are experiencing.

So we are not far away from having a database, which is going to be powered enough that could be the main backbone of our submission to FDA for indication expansion of this test from CRC screening to multi-cancer detection. Still, there are some work for us to do on that front, but the commercial scale of Shield is really paving the path for us to get to that point in the near future.

All right. And just like for context, the other MCED, FDA submission right now has 175,000 patients in the -- maybe even more in the submission. So would your -- would the data points that are included in what you just said basically like eventually add up something like that or bigger?

I mean if you just look at even the guidance for our CRC testing this year of 270,000 to 285,000 testing this year. You can get a sense of the commercial scale that we are talking about. So it's not going to take us long until we get to this point of having a major clinical database in our hand.

Okay. And then on kind of commercialization and sales force. So you have, I think, 400 reps right now plus a DTC effort. Can you talk about the balance between those 2 functions basically?

We have a skilled commercial infrastructure right now, more than 400 reps in the field, which at steady state, we are going to scale it to 600 to 700. So we are -- we made significant progress and dramatically actually build that commercial infrastructure. Our national DTCs and influencer campaigns are live at national level. Maybe some of you guys have seen those kind of ads.

And in terms of the investments, still majority of our investments are going in the personal promotion and the field force side, but a material fraction is going in DTCs, and we expect that to continue as we go to next year.

All right. Perfect. And then maybe, Helmy, going back to you on the G360 Liquid approval recently. So that's great. I mean, did that impact volumes at all kind of maybe end of 2Q or early third quarter so far? And then also, what's the path for the ADLT rates and trying to get to the 8,500 rate?

Yes. I mean right now, we're phasing the launch. So most of it will be launched really at -- once we get ADLT designation. But yes -- and obviously, we got it late in Q2, so it really didn't impact to the Q2 results. But we're certainly seeing a lot of excitement around that approval, and we're hopeful that, that will be something we can continue to lean into as we sort of make more progress in the field.

In terms of ADLT, we've been, I think, positioning it around sort of first half of 2027 event. And so yes, we're going through the sort of motions of getting a PLA code and then submitting for ADLT, which are the 2 steps required for that.

Yes. And then the ASP for that therapy selection business could be maybe 5,000 or so by -- in the next like maybe a year or 2. Is that kind of the guidance?

Yes. I would say that there are a couple of steps along the way. There's first getting Part B Medicare, then Medicare Advantage and then finally, some of the commercial payers. So it's at least probably 12- to 24-month process to get to something close to what you mentioned.

Okay. And then on the ADLT notes, do you still plan on trying to get Reveal ADLT status on payment right or...

Yes. I think for all our products long term, our intention is to get to ADLT status. With Reveal, we still have some items around the novelty pathway, but I think we have a full plan B around FDA approval, and so we're working on some of that. And then the same thing with tissue, we see that getting ADLT at some point as well.

Perfect. And then sticking with Reveal, so you don't have -- you're trying to get coverage for MolDX for breast cancer and therapy monitoring. And those are -- the volume for those indications has been growing really fast, obviously. So once MolDX turns that coverage on, what could that mean in terms of that revenue stream for you?

Yes. I think the exciting thing is just how much demand we're seeing in the market right now ahead of reimbursement. And so I think that really is a leading indicator for really the fact that we have product market fit with these products out there. There's a lot of people who love using them.

And really, the next shoe to drop is just getting reimbursement and getting the ASP up for those products. I think we're also excited about expanding indications beyond those as well. We have a lot of work we've done in terms of improving the -- expanding the platform beyond just breast, lung and colorectal cancers and therapy monitoring. And so we see a lot of opportunity there over the coming years for increased expansion, increased volume as well and then obviously, Reveal Ultra as well.

Yes. And Reveal Ultra, I was going to say like that's reimbursement at some point in the next year or so. How important is it to really round out the Reveal portfolio in order to compete? Because I feel like that's kind of the name of the game in MRD. It's kind of having like a portfolio of products because it's very obvious what you're doing on the therapy selection side, Shield side, but Reveal is a little bit more behind the scenes almost. So what's your take on that?

Yes. So we think the market will be similar to how things have evolved on the therapy selection side of things where there is a need for both products, both liquid products and tissue products. We think there are 2, I think, very large market opportunities around tumor-informed and tissue free. I think with tissue free, you get results much faster. You have a wider catchment in terms of detecting disease that may not be the same as what was taken out with surgery.

And then obviously, with some of the sort of ultrasensitive tumor-informed approaches, you can go very, very deep. And so we think there's -- but those tests tend to be slower and more narrow in terms of what they detect. And so I think there is really a place for both in the large 18 million sort of patient population that is part of the MRD market. And I think the eventual winner, I think, will have best-in-class products on both sides.

All right. And I mean there's been a lot of kind of consolidation in the MRD space recently in the past few months. What's your thoughts on maybe a bolt-on given all your cash to enhance that portfolio?

We look -- we have a very, I would say, active corporate development group. We want to do things that are sort of meaningful in terms of the pipeline that we have. Obviously, we have a very robust pipeline, a lot of innovation that's happening inside of Guardant, a lot of great product trajectories. But when we find things that make sense, we execute on them. We had a small tuck-in late last year with MetaSight, but there's hardly a deal that sort of happens that we haven't sort of at least looked at and kicked the tires on.

Yes. And so it feels like your epigenomics and your multiomics kind of platform can enable you to break into multi-disease market, $300 billion is the TAM basically. So -- but also acquisition could help as well. What -- I mean, what's kind of like a good way to think about the timing for Guardant to break into something outside of oncology?

So for some indications already, we have some proof-of-concept data. So let us make more progress on those matters, and we will talk about it more firmly in terms of time line. But definitely, we are seeing some exciting matters.

When you're thinking about these very wide, highly sensitive epigenomic technologies that we have, we are finding abnormalities in body, which is the source of it could be way beyond oncology when we are talking about organ health monitoring, when we are talking about fatty liver, when we are talking about neurodegenerative diseases like Alzheimer, dementia. For some of these, actually, we have proof of concept that looks like during the early phases of developing that disease, we can find some signatures in their blood. So we are very excited with it. Early days, let us make more progress and we see what happens.

All right. It's exciting. But generally, the strategy might be to piggyback off of the personalized medicine or the precision medicine kind of market in different diseases perhaps. Is that kind of where you're -- like the way you do in oncology?

Yes. I mean when you look at actually even the concept of screening, MRD, treatment management, that's just not specific to oncology. Oncology was one of the leading disease areas, but like just look at neurology, even the last panel that you had, the progress that's happening there with multiple therapeutic opportunities, patients need to get monitored about the activity of disease like similar to MRD.

And then we need to find some early development of some of these diseases in patients who have symptoms or even average risk people. Effectively, the continuum of care scenario that we have for oncology is replicatable in other diseases.

All right. Awesome. And then maybe, just sticking with you on Shield again. Just thinking about the path forward, it's just been -- it's been so strong, so impressive. It's not -- it's still inflecting basically and it's got UnitedHealth coverage and ACS. But what -- how could that product really like surprise investors, let's say, maybe next year and going forward? I mean USPSTF could be a factor. What else could -- we should be looking forward to?

Well, if I tell you the surprises, it's not going to be a surprise. So stay tuned.

But I guess on that note, though, what is your thoughts on guideline inclusion in the next couple of years? It's been very volatile in that group.

Yes. I mean, the reality is there's a bunch of uncertainty there. Like we are taking our position that based on some of the activity that's happening, we are not changing our projection of bringing any time line forward. So still task force, we are considering it maybe late '27, '28 kind of time frame.

Having said that, it's kind of interesting that finally, they are going to meet sometime this quarter after 1.5 years of not meeting potentially with the new membership. But the field has changed. I can look at some of the commercial payer actions that we are seeing. So other players are well aware of what's happening. And I think some decision-makers and stakeholders are not going to wait for USPSTF decision, but we'll see how it goes.

All right. And then one kind of interesting question I get sometimes is like why order the single cancer screening test when I can have one for 50 cancers or maybe 10, but 10 isn't offered by U.S. just yet basically, right, FDA approved. So why choose Shield rather than the one I just referenced?

So Shield is multi-cancer detection. I think that there is some minimum performances that you need to hit for some specific single cancer type in order to be considered even as a screening test. Like some of the multi-cancer detection technologies, which are out there, they are not going to qualify as a CRC screening test. They are not meeting those bars. They don't have the clinical evidence to support that.

So these are 2 different kind of categories. You need to have high performance in order to qualify for screening, which Shield is, and also we can do multi-cancer detection. I think future for this kind of a pathway that we pick for our Shield platform is very bright.

Awesome. Thanks AmirAli and Helmy.

Yes, thank you for having us.

Hello, everyone. Thank you for joining us, and welcome to the Guardant Health Second Quarter 2026 Earnings Call. [Operator Instructions]

I will now hand the conference over to Zarak Khurshid, VP of Investor Relations. Zarak, please go ahead.

Thank you. Earlier today, Guardant Health released financial results for the quarter ended June 30, 2026. Joining me today from Guardant are Co-CEOs, Helmy Eltoukhy; and AmirAli Talasaz; and Chief Financial Officer, Mike Bell.

Before we begin, I'd like to remind you that during this call, we will be making forward-looking statements within the meaning of federal securities laws. These statements involve material risks and uncertainties that could cause actual results or events to materially differ from those anticipated. This call will also include a discussion of non-GAAP financial measures, which are adjusted to exclude certain specified items.

Additional information regarding material risks and uncertainties as well as the non-GAAP financial reconciliation to most directly comparable GAAP financial measures are available in the press release Guardant issued today as well as in our 10-Q and other filings with the SEC. Guardant disclaims any intention or obligation to update or revise financial projections and forward-looking statements. whether because of new information, future events or otherwise, except as required by law. The information in this conference call is accurate only as of the live broadcast.

With that, I would like to turn the call over to Helmy.

Thanks, Zarak. Good afternoon, and thank you for joining our second quarter 2026 earnings call. Starting on Slide 3. The platform we have built at Guardant is enabling four of the largest opportunities in precision medicine. Therapy selection, recurrence monitoring, cancer screening and ultimately, multi disease screening. Together, these represent nearly $400 billion in potential markets all powered by the same smart platform and that compounding technology data and clinical insights to generate across the disease continuum. Q2 is a landmark quarter in advancing that vision.

During the quarter, we received FDA approval for Guardant360 Liquid CDx as well as approval for a higher throughput, lower COGS Shield workflow. In addition, we achieved two significant Shield milestones inclusion in the American Cancer Society's colorectal cancers cleaning guidelines and just this month, a major coverage decision from UnitedHealth Group. Together with continued broad-based growth across the business, these results demonstrate that we are steadily turning our Smart Platform Vision into clinical impact and durable growth.

Before I share our results in more detail, I'd like to share a story that illustrates the real-world impact of our tests. Maria was a 46-year-old mother of two living with metastatic breast cancer. After surgery, chemotherapy, endocrine therapy and later progression on multiple lines of treatment, her care team faced a familiar but frustrating question, what next? Her disease had become harder to control. Tissue was limited from prior biopsies and may not be representative of her current disease and another invasive procedure would have delayed treatment decisions. Our oncologist ordered a Guardant360 Liquid test to provide a comprehensive real-time view of her cancer through a blood draw.

The result changed the conversation. Guardant360 Liquid identified homologous recombination deficiency or HRD which occurs when cells lose their ability to actively repair double-stranded DNA breaks. Armed with this new biological insight, Maria's care team had greater confidence that her cancer may be more responsive to a DNA damage response strategy as opposed to another empiric chemotherapy. Maria's oncologists shifted her treatment plan to a biomarker-informed approach that included platinum-based therapy, which we responded well to with manageable side effects.

Turning to our revenue performance on Slide 4. We delivered $335 million of revenue in the second quarter, representing 44% year-over-year growth. The growth was strong and broad-based across our oncology, biopharma and data and screening business lines.

Taking a closer look at our Oncology business on Slide 5. Oncology revenue grew 38% year-over-year, driving Q2 revenue of $219 million. Oncology test volumes rose 63% to approximately 104,000 tests, up from 64,000 in the prior year period with strength across all products.

Turning to Slide 6. The tremendous 63% growth in oncology volume represented another quarter of acceleration reflecting the increasing strength of our portfolio across both therapy selection and MRD. Guardant360 Liquid year-over-year volume growth accelerated from the first quarter, delivering greater than 30% growth, benefiting from continued smart platform adoption. Guardant360 Tissue volume growth also accelerated in the quarter, and remains our second fastest-growing product. Reveal continues to be our fastest-growing product with volume growth accelerating again to more than 100% year-over-year, reflecting continued strength in MRD and growing adoption of the therapy monitoring use case.

Moving to Slide 7. I want to spend a moment on what we believe is one of our most underappreciated assets, our data. Every patient we test deepens a proprietary data asset that is difficult, if not impossible, for others to replicate. Today, that repository spans more than 1.3 million patient tests and over 700,000 epigenetic profiles across more than 100 tumor types. This is the raw fuel that powers Infinity AI, enabling the discovery of novel biological signatures the development of new clinically actionable smart apps and the acceleration of drug discovery for our biopharma partners. At ASCO in June, we showcased several innovative new tools built on our Infinity AI platform and we are seeing a very strong positive response.

Turning to Slide 8. In May, we received FDA approval for Guardant360 Liquid CDx, the most advanced FDA-approved liquid biopsy panel with 100x more content versus our legacy FDA-approved CDx product. Guardant360 Liquid CDx is significant for several reasons. Most notably, it reinforces Guardant's leadership in the field of liquid CGP testing with Guardant360 Liquid CDx representing the only FDA-approved liquid biopsy test, integrating both genomic and epigenomic content. Overtime, Guardant360 Liquid CDx will help to simplify our therapy selection portfolio by consolidating multiple offerings into a single product.

We're also excited by the potential for Guardant360 Liquid CDx to complement Guardant360 Tissue to drive greater adoption. We remain on track to obtain ADOT designation for Guardant360 Liquid CDx in the first half of 2027. In June, we began a phase rollout of Guardant360 Liquid CDx to our U.S. customers. We plan to offer widespread availability of the test following ADLT designation. This approach is intended to ensure a smooth reimbursement transition to the new test. The FDA approval in the second quarter represents one of the most significant regulatory milestones in our company's history and the feedback from customers thus far has been incredibly strong.

Turning to Slide 9. Reveal continues to perform at an extremely high level with volume growth accelerating for the third quarter in a row to well above 100% year-over-year. We believe Reveal remains the most validated and highest-performing tissue free MRD solution with a 5-day turnaround time. Once again, we experienced strong MRD uptick in the second quarter across major indications and Reveal therapy monitoring continues to stand out as a major volume growth driver in its second full quarter after launch.

Reveal is uniquely suited for therapy monitoring in late-stage cancer, helping predict therapy response, months before imaging and with seamless cannotivity to Guardant360 Liquid. It can help physicians to act sooner and with more precision. Late-stage cancer therapy monitoring alone is a multimillion test annual opportunity that remains largely untapped. We continue to be excited about the commercial momentum behind Reveal, and we remain on track to launch Reveal Ultra later this year, which we believe will be the most sensitive tumor-informed MRD test.

Turning to Slide 10. We continue to make progress advancing our Reveal data and publication pipeline. As a reminder, we have submitted data to MolDX for coverage for breast cancer surveillance, immuno-oncology monitoring and chemotherapy monitoring, and those initiatives continue to progress.

Shifting to our biopharma and data business on Slide 11. Revenue grew 9% year-over-year to $61 million, which marks a record quarter. Our companion diagnostic franchise continues to build momentum. We now have 28 CDx approvals with 4 added in the first half of this year alone. This reflects the strategic value of our smart platform to leading biopharma companies.

During the quarter, we received FDA approval for Guardant360 CDx as a companion diagnostic for Boehringer Ingelheim for Nexeos, the first targeted therapy approved for adults with HER2 or ERBB2 mutant advanced non-small cell lung cancer as an initial treatment option. We also received FDA approval for Guardant360 CDx as a companion diagnostic for Arvinas and Pfizer's, Veppanu for ER-pos/HER2-negative ESO1mutated advanced breast cancer. We also announced a collaboration with Nuvalent to develop companion diagnostics with an initial focus on Guardant360 tissue.

With that, I'll now turn the call over to AmirAli for an update on screening.

Thank you, Helmy. Moving on to Slide 12. We developed Shield from the ground up as a multi-cancer detection platform. Shield is clinically validated for detection of 10 different cancer types and is approved by the FDA for colorectal cancer screen as its first indication.

When a physician orders a Shield blood test for CRC screening, they can opt in to receive multi-cancer detection results report covering 9 additional cancer types beyond CRC. The release of this report is contingent on patients authorizing the release of their medical records to Guardant as part of our data collection initiative. We are very pleased with the progress in multi-cancer data collection and are excited to see the majority of Shield ordering physicians opting in to receive MCD reports. With colorectal cancer screening still representing such a significant unmet need, CRC remains our primary commercial focus.

Now moving on to Slide 13 for an update on the screening business. Q2 was another fantastic quarter for Shield. We delivered $53 million of Shield testing revenue driven by approximately 66,000 tests compared to $15 million of revenue and approximately 16,000 sales in Q2 of 2025.

Turning to Slide 14 shows the evolution of Shield sales over the last 8 quarters overlaid with the important guidelines, commercial partnerships and coverage wins that have been instrumental in driving recent demand, and that gives us confidence in future growth. I will discuss a few of these significant wins in greater detail shortly. We are now well into our second year of commercial launch and the business continues to fire on all cylinders.

Moving on to Slide 15 to discuss our major screening highlights. We saw exceptionally strong volume growth in the quarter, driven by commercial scale DTC momentum and our Quest collaboration. Shield was included in the American Cancer Society's colorectal cancer screening guidelines, making still the only FDA-approved blood test included in both ACS and CCN guidelines. And United Health Group, the largest commercial insurer in the United States announced it will begin covering shift for colorectal cancer screening in adults 45 and older. Moreover, we are excited to report that last week, we received FDA approval for a higher throughput, lower COGS Shield workflow.

Let's focus on the latest scale Shield commercial engine on Slide 16. Shield's commercial reach continues to expand rapidly on personal promotion campaigns, health system engagement and [ e-mail ] connectivity. We are happy to report that our field organization now stands at over 400 professionals nationwide. In addition to our internal sales team, the Quest collaboration has been a success. We are encouraged with how nationwide EMR access and co-promotional activities with their team have developed in the first full quarter since the relationship went live in the field. In addition to these initiatives, we have built and expanded our dedicated health system team to more than 30 people and have been encouraged by the engagement within large accounts.

Turning to Slide 17. Patient access to Shield blood test continues to expand at a rapid rate. Shield was added to the NCCN guidelines in June 2025 and to the American Cancer Society guidelines in May 2026. ACS guideline inclusion is particularly important because it triggers state-level coverage mandates in roughly a dozen states for commercial payers. An exciting result of these guidelines wins, has been positive momentum in our payer discussions and the sooner-than-expected UnitedHealth coverage policy update that I mentioned earlier. This coverage will be effective starting on August 1 which includes Shield as a covered primary colorectal cancer screening option for average risk adults aged 45 and older. UnitedHealth is the largest commercial insurer in the U.S. and the first major insurer to cover Shield.

Turning to Slide 18. To put these commercial coverage wins into context. There are approximately 120 million average-risk individuals in U.S. eligible for colorectal cancer screening, representing a $50 billion U.S. addressable screening market. As a result of ACS guideline inclusion and the UnitedHealth coverage policy, we believe that approximately 70 million lives or roughly 60% of the market is now covered for Shield blood tests.

Turning to Slide 19. Last week, we received FDA approval for a higher throughput, lower cost Shield workflow, and that workflow will be live in production in, I guess, for all new incoming samples -- this workflow improvement will increase efficiency in running the test and will reduce the cost per test. Furthermore, it will improve the scalability of our existing lab operations. As a result of this development, the much stronger-than-expected demand and UnitedHealth coverage news, we are accelerating investments to continue to build our lab capacity ahead of rapidly increasing volume. We are excited about all the progress across multiple fronts at Guardant Health.

On behalf of Helmy and myself, I want to express our deepest gratitude to our leaders and the whole Guardant team watching this team's focus, integrity and sheer dedication to our mission continues to inspire us both every single day.

With that, I'll now turn the call over to Mike for more detail on our financials.

Thanks, AmirAli. Turning to Slide 20. I'll walk through our second quarter results, unless otherwise noted, growth rates are year-over-year. Second quarter revenue reached $335 million, up 44%. Growth was broad-based with strong contributions from oncology, biopharma and data and screening. Oncology revenue was $219 million, an increase of 38%. Oncology test volume grew 63% to approximately 104,000 tests, reflecting strength across the portfolio.

Within the portfolio, Guardant360 Liquid volume increased more than 30% driven by continued adoption of our Smart Apps. Guardant360 Tissue accelerated from first quarter levels and remained our second fastest-growing oncology product, reflecting the product enhancements introduced over the past few quarters. Reveal again led the portfolio in growth with volume more than doubling year-over-year as MRD adoption expanded and therapy response monitoring contributed meaningfully. Oncology ASPs were broadly stable sequentially, and our submissions to MolDx for Medicare reimbursement covering breast MRD and immunotherapy and chemotherapy response monitoring continue to progress.

Our biopharma and data business delivered record quarterly revenue of $61 million, up 9%, reflecting the increasing strategic value of our smart platform and Infinity AI offerings to biopharma partners. Screening revenue was $53 million compared to $15 million a year ago. Shield volume increased to approximately 66,000 tests from 16,000 a year ago. ASP was approximately $800 per test with reimbursement remaining strong across Medicare fee-for-service and Medicare Advantage.

As expected, the mix of commercially insured patients under age 65 increased in quarter ahead of broader reimbursement coverage. With Shield now included in ACS guidelines and UnitedHealthcare coverage beginning in August, we expect the commercial mix to continue to increase in the second half of the year.

Turning to Slide 21. As AmirAli noted, the FDA recently approved a higher throughput, lower COGS Shield workflow. This marks a significant step forward in our efforts to reduce Shield cost per test. When fully implemented on our lab operations, the new workflow will produce a step-down in Shield cost per test. Combined with additional efficiencies from increasing scale, we expect that by the end of 2026, Shield cost per test will reduce by roughly 15% from the current level of approximately $410. Beyond 2026, further scale benefits and major automation initiatives are expected to drive the next wave of reductions and support our $200 cost per test target in 2028.

Turning to Slide 22. Second quarter non-GAAP gross margin was 67% compared with 66% a year ago. The improvement reflects lab efficiency, disciplined execution and tight cost control. As planned, we completed the Guardant360 Liquid transition to NovaSeq X in May, reducing cost of test by approximately $200. That benefit together with the planned Shield cost reductions will help support continued strong gross margins in the second half, even as our product mix continues to evolve. Non-GAAP operating expenses were $280 million, up 34% with the increase concentrated in commercial investment. Sales and marketing expense was $172 million compared with $108 million a year ago as we continue to expand the screening sales infrastructure advanced Shield HCP and DTC programs and supported oncology growth.

Adjusted EBITDA loss was $56 million compared with a loss of $52 million in the second quarter of 2025. Quarter-end cash investments were approximately $1.2 billion, and free cash flow burn in Q2 was $70 million compared with $66 million a year ago. The year-over-year increase was due to additional CapEx investment in screening lab automation and broader infrastructure to support higher test volumes, greater processing efficiency and improved turnaround times.

Turning to Slide 23. Our first half results and the progress since our last call give us greater visibility into the balance of the year. We are raising full year 2026 revenue guidance to arrange $1.34 billion to $1.36 billion, representing growth of 36% to 38%. For oncology, we now expect revenue growth of approximately 30% and volume growth of approximately 50%. The outlook reflects continued smart production of Guardant360 Liquid, strong commercial execution and the impact of recent product upgrades in Guardant360 Tissue as well as continued growth in Reveal across MRD and therapy monitoring.

Our biopharma and data outlook is unchanged at low double-digit growth, supported by recent strategic partnerships and continued good progress across the companion diagnostic pipeline. For screening, we are raising revenue guidance to a range of $218 million to $230 million and now expect 270,000 to 285,000 Shield tests. The higher outlook reflects strong demand and commercial execution as well as greater confidence following ACS guideline inclusion and UnitedHealth coverage, which becomes effective in August.

Our full year non-GAAP gross margin outlook remained 64% to 65%. The range incorporates lower testing costs for Guardant360 Liquid and Shield in the second half, partially offset by product mix as Shield and Reveal volumes scale. We intend to continue to reinvest incremental screening gross profit to support commercial expansion. As a result, we now expect 2026 nonoperating expenses of $1.08 billion to $1.1 billion, representing growth of 20% to 22% compared with 2025. We now expect full year free cash flow burn of $195 million to $205 million, $10 million above our prior outlook and an improvement compared with 2025.

As mentioned, this revision reflects CapEx investments to accelerate the expansion of Shield's lab capacity supporting anticipated growth over the next several years. We continue to expect the rest of the business, excluding screenings to generate positive free cash flow in 2026 with year-over-year improvement in cash generation and we remain committed to achieving company-wide cash flow breakeven by the end of 2027.

Turning to Slide 24. Several catalysts we discussed last quarter are now in hand. In oncology, the NovaSeq X transition is complete and Guardant360 Liquid CDx is FDA approved. Our priorities are continued expansion of smart platform apps the larger Reveal Ultra and broader Reveal reimbursement. The ESR1 monitoring launch remains contingent on FDA approval of camizestrant.

In biopharma and data, our priorities are to continue to advance CDx programs, broaden strategic partnerships and scale Infinity AI. In screening, we obtained ACS guideline inclusion and are excited about the United Healthcare coverage, both of which will help broaden access and adoption of Shield. We're also expanding Shield internationally through our self-pay channel.

To close, Q2 demonstrates the breadth of our growth and the progress we are making in driving efficiencies across our operations. We are investing in the areas with the greatest long-term potential while maintaining our commitment to cash flow breakeven.

With that, we'll open the call for questions.

[Operator Instructions] Your first question comes from the line of Kyle Mikson with Canaccord.

Congrats on a great broad-based performance in the quarter. Just on screening though, first, UnitedHealth and ACS, obviously open the market up to the under 65-year olds. Could you elaborate on the near and the long-term ASP and the volume impact? I guess, after August, the volume tailwind could be pretty material, but pricing hasn't been finalized, I assume, for these commercial plans. And just secondly, kind of quickly, like on USPSTF. With all this happening, what's your thoughts on this late August meeting? Do you still think a late '27 or early '28 time frame for inclusion there makes sense?

Thank you, Kyle. Obviously, we are very excited about this recent development with both ACS and UnitedHealth coverage. As I mentioned in the prepared remarks, actually now roughly 70 million lives are covered for Shield, 60% of the whole market. This UHG win could actually give us some interesting benefits like we are excited to see how the rest of the year would play out. It could be a tailwind for the volume. It would help us to strategically step-by-step build our commercial side of the volume, so not just 65 and above, but actually younger patients, make sure they get actually access to this breakthrough technology.

ASP has got to take some time though like ASV in order to see the impact. We need to obviously, go through some kind of conversations with them, but also show the history of collection from them in order to be able to accrue some of the upside upfront. So on ASP side, we need to be more patient. USPSTF it's our expectations, as it was before. So it looks like new members are going in place. It looks like the August meeting is going to happen.

But in terms of our expectation, we are not changing anything. So we are monitoring to see what happens. And it's interesting, as I mentioned, solve the payers even before USPSTF are engaging in conversations with us. And we'll see what happens.

Your next question comes from the line of Subbu Nambi with Guggenheim.

Congratulations on another record oncology volume in Shield quarter. As we think about oncology volume guide, could you give us some puts and takes on the 50% guide rate? Is this largely from Reveal in metastatic states? And how is poor patient testing cadence looking today? I know it's early and looking to Q3, given the tough comp in G360, how should we think about G360 volume growth?

And I know I'm tacking on multiple questions, but one question for you, AmirAli. How did the United coverage come about? It was surprising to us. None of us had that in our 2026 bingo card. So how might that influence other private payer coverage in the absence of even USPS?

Thanks, Subu. Good question. Yes, we're really excited about what we saw in the quarter in terms of oncology volumes. Obviously, we had a tremendous sort of volume ramp that we saw. And it was really broad-based in terms of the beat. We saw great volumes from 360 growing over 30% year-over-year. Tissue continued to accelerate obviously, than $360 million and then Reveal was also over 100%.

And so I think all of them are really going to be contributing to sort of continued strong volume for the second half of the year. And obviously, we have strong sort of comps for Q3 and Q4 for 360. But I think we're very confident that we can continue the momentum. We're seeing at least in the first half of the year on all of the products going forward and so that we can hit that 50% mark that we guided to. I don't know if Mike wants to add?

I mean, no, just to reiterate, Homi, that I think our guide now of 50% full year oncology volume growth is incredibly strong. So yes, I mean, we have -- I think we have tough comps now every quarter. So we'll continue to manage that. But I think our guide, again, for Q3 and Q4 is implying very strong oncology volume growth.

Regarding UnitedHealth, it was unexpected for us to, it was much sooner than what we thought it's going to happen. Having said that, we have multiyear relationship with United because of our oncology products and coverages. We have the relationship, and we had multiyear conversations with United about the value of the Shield and what it could offer.

There is also something in the payer landscape that nobody wants to be first, nobody want to be last. So again, still, we don't expect any major wins in short term by any other major payers. Having said that, again, nobody want to be last to, and we are excited with some of the conversations that we are having with some plans. We see what happens -- what will happen.

Your next question comes from the line of Puneet Souda with Leerink.

And again, congrats on this impressive growth that you're seeing in the core business as well as Shield. Is there a way to sort of characterize this? I mean, as I pointed out before, this is an assay that's been on the market, G360 has been on the market. You revamped it. It's been on the market for 10 years plus. And it's growing 30%. Now it's running -- it appears to be growing even more faster. Your portfolio is running faster. Sort of where are we in this S curve of growth and then on the Shield side, merely, just wondering how should I think -- how should we think about the drivers for upside?

Is it the sales reps, DTC ads, what are some of those? And how should we think about if there is any third and the fourth quarter, sequential rent growth that if you can provide on Shield?

Yes. Thanks for the question, Puneet. We're very excited about what we're seeing. And it's -- what we obviously built the product to and how advanced we believe it is compared to sort of the landscape right now in the liquid biopsy market. It really is one of the most comprehensive tests out there. It covers broadly all the genomic markers of relevance, but really the only test that has integrated genome-wide methylation coverage, which is really driving a lot of the, I think, really exciting sort of next-gen applications of liquid biopsy.

And frankly, I think we're just scratching the surface in terms of what's possible with this platform. And I think many physicians are just starting to get sort of the experience of using it with patients. And it's -- when you get those hits when you find something that you couldn't find before you find an option for a patient, it takes time to sort of get those experiences. And I think we're really leaning into it now now that it's been on the market for a few quarters.

And we're very excited about the pipeline in terms of other apps that we have in development that will be coming out soon. So we think this is something that we can continue to lean into not just for the sort of one test per patient era that we're in right now. But when we started thinking about patients using a liquid biopsy, Guardant360 test at every progression. And that's still not something we've leaned into. That's a big market multiplier and why we believe we can continue to sort of lean in to this growth of 360 for years to come.

There was something about Shield quickly to answer that. The sequential growth of Q2 over Q1 was super strong for us, 22,000 step-up. There were multiple factors that compounded at once. We launched this Quest co-promotion. We launched our DTC. We are adding to our field force. And there is some nonlinear effects that we are seeing that the productivity of our reps have gone up in a very interesting way when we are doing the co-promotion with Quest, and we have our DTC in the air.

There were multiple factors all combined between Q2 and Q1. So we don't expect multiple new things all hitting at once in Q3. Having said that, we are very excited of what we can do in the second half, like we increased our guide by 40,000 samples, which translates at the midpoint, the guide that we put out there, like sequential growth of 12,000 Q-over-Q. We don't want to get ahead of our skis with the fantastic Q2 results that we have for the rest of the year and we're very thoughtful. I think it's a very reasonable guide for the second half of the year for us.

Your next question comes from the line of Mark Massaro with BTIG.

Congratulations on another great quarter. Helmy, I know in the last couple of years, you've talked about how you'd like to sort of reframe how pricing -- the value of diagnostic tests in the industry. The reason I'm asking this question is like Subbu said, the United coverage really caught everybody by surprise. So as we think about your ADLT rate of $1,495, how should we -- how are you thinking about negotiating with United, what is your appetite for a discount and then you talked about how you're encouraged with other conversations with commercial payers.

It would seem logical that other payers would probably follow, but I was curious if you could just speak to the importance of ACS and NCCN. And to what extent those endorsements in some ways, might derisk USPSTF

And that's for Amir, I'll let him answer that.

Yes. So in terms of pricing negotiation, like we just got the coverage, so let us go through that process and see what's going to happen. It's very typical in diagnostics, Medicare pricing is the center piece of conversations and our pricing is very transparent to everybody when they make even the coverage decision.

So -- but we'll see how it goes. In terms of derisking, I think UnitedHealth decided to act before USPSTF. And we are seeing some additional conversations with other payers. Definitely, we are getting the attention. UnitedHealth coverage decision is getting the attention by other people.

Our progress in the field in terms of the impact we are showing is getting the attention, and we have a scaled team in managed care team that have all the connections and relationships and with a bunch of those people, we have multiyear conversations about Shield. But again, we'll see how it goes. We don't expect any major wins for the rest of the year. We haven't included anything in our guide in terms of additional wins, and we'll see how it goes.

Your next question comes from the line of Dan Brennan with TD Cowen.

Maybe I'll just have one on ADT. So first off is kind of 8,500 plus or minus the right price merely -- excuse me, Helmy. When we did the math, we came up with about a 10% increase to revenues in '27, 20% in '28, just based upon the realized price that you'd be able to capture. So anything you could share about whatever price you pick, like what type of MA and commercial realized price increases, what's a reasonable way to think about that? And then importantly, whatever the revenue impact is -- can you just help us through what the drop through rate will be? Like how much of that revenue upside would you plan to reinvest back in the business? And how much of it will accrue to the pretax volume?

Yes. No, I think we're going through the ADLT process now. We're expecting a price of $84,55. And so that will be an uplift from our current Medicare price of $5,000. And then that would be an immediate increase. It will take time for Medicare Advantage and commercial payers to sort of change the price in line with the new Medicare price. And I think we've seen that in the past when Guardant360 CDx got ADLT and ADLT pricing. It can take sort of 12 to 24 months for that to flow through. So I would expect once we get that ADLT, yes, we'll see a nice uptick for all ASP for Guardant360, but then it should continue to improve over, again, the next sort of 12 to 18 months.

Yes, investing the incremental gross profit. I think that's -- we've been sort of doing that over the past sort of 12, 18 months on the screening side of business, and that's been allowing us to increase our investments, specifically on the commercial side. I think with oncology, if and when we do get a higher ASP and incremental gross profit. We will allow some of that to drop down to the bottom line.

I think we've said it many times, but we're very focused on getting to cash flow breakeven as quickly as possible. And so that could give us the ability to accelerate our time line, which is currently sort of Q4 2027. But we'd also want to take some of that gross profit and reinvest it back in the business. I mean, we continue to be a company of innovation. I think we want to continue to do that. But we would also on the oncology side of the business, one to continue to invest on our commercial operations. So I think hopefully, we'll be able to do both, and it will start to -- we'll start to have a very nice P&L as and when that comes.

Your next question comes from the line of Daniel Markowitz with Evercore

Congrats on the quarter and all the progress the last recent history as well. So when I look back at the Investor Day last year, you gave some helpful targets for 2028. And there have been like I just said, lots of positive development since then.

So firstly, I just wanted to ask your high-level views on how things have trended and what it might mean for those targets. And then double-clicking on G360, tacking on to Dan's question. Now the table is set for ADLT, should we think about the ASP uplift with the new list price taking you up to closer to $5,000 rather than the prior target was closer to $3,300.

And then I also wanted, lastly, just more color from this ASP uplift -- if you drop that straight down to gross profit, it does imply really nice upside to the margins and the profitability inflection. I just wanted to get more color on that and how you think about what to reinvest versus how much to drop down and whether the math is right and this really could be a very meaningful profitability inflection.

Yes, I'll take that. Again, just to sort of reiterate at our Investor Day last year, we sort of increased our 2028 revenue target. It would have previously been $2 billion, and we increased that to $2.2 billion which sort of inferred a growth rate over 3 years of just over 30%.

So I would say that so far so good. I think we're doing very well against that target. Our current guidance now for the full year of '26 is 36% to 38%. So I think against what we need to do over that 3-year period, we're doing very well. I don't think we're in a position to sort of change that target now. But I think where we are in the middle of '26 just gives us a lot more confidence that we can achieve that $2.2 billion.

Yes, I think the other question was related to the ADLT rate at [ 8455 ]. And would that lead to a Guardant360 ASP of around $5,000. That's probably in the ballpark on a sort of a long term. I just mentioned on the last answer, it probably take 12, 18, 24 months to sort of get to that level. But realizing overall sort of 60% of the Medicare rate, that's currently where we are with Guardant360.

So I think it's -- that sort of $5,000 level is achievable. And yes, I think basically on the profitability, the incremental gross profit and how we would manage that, I think we talked about that on the last question with Dan. And again, I think it would be a mix of letting that drop down -- some of that drop down to the bottom line, hopefully accelerating our path to breakeven, but also reinvesting back in the business in innovation and on the commercial strength of the company.

My apologies comes from the line of Casey Woodring with JPMorgan.

Congrats on the print. Helmy, maybe can you give us a sense of how therapy monitoring volumes are tracking and how those are contributing to the greater than 100% volume growth in Reveal and any way to quantify or frame the revenue opportunity there once you turn on reimbursement for IO and chemo? And then as a follow-up on G360, would just be curious to hear if you're seeing any material uplift in volumes that are driven by the FDA approval if that's been a real needle mover for doctors that maybe you have been on the sideline in terms of moving over from tissue.

Yes. Great question, Casey. We're very excited about what we're seeing with therapy monitoring. I mean that said, we're seeing really good traction with MRD and the Reveal volumes. And -- but therapy monitoring, I think, is a I would say maybe underappreciated opportunity in the market. This is, I think, the future of oncology in terms of moving from biopsies and scans to really just using blood quantitatively to both treat and modern patient response to therapy.

So we're seeing very, very good uptake from our G360 orders really want to sort of move into the future of Precision Medicine here. And yes, and we think this is a great leading indicator for some of the -- sort of reimbursement over the finish line, it's going to be a very, very strong business for us. If you think about it, there are 1 million late-stage patients. It's a multi, multimillion sort of testing opportunity there just for therapy monitoring. If you think about monitoring those patients a couple of times during each course or each line of therapy.

And so I think it's could be, I think, narrowly as big as maybe even the MRD opportunity testing point of view, at least in the active cancer patient segment. And then in terms of FDA approval, it really happened sort of late in the quarter. So I think very early to sort of comment on that. And because we're doing a phased launch, it's having a positive impact, but nothing, I think it won't be as big of an impact as when we finally sort of do a full launch once we get ADLT designation.

But certainly, we're seeing a lot of positive reception and a lot of excitement from physicians and it's certainly something that we're going to lean into in the quarters.

Your next question comes from the line of Kallum Titchmarsh with Morgan Stanley.

Maybe just one for Helmy, it would be good to get a little more color on Reveal Ultra. I guess perhaps just walk us through the indication road map. And then would love to just understand the commercial strategy in more detail as you go about capturing share there.

And then for AmirAli, just on the multi-cancer detection front, perhaps just walk us through the opt-in rates that you've been seeing on that and then how you're using the data that you've been generating from those tests.

Yes, it's -- in terms of Reveal Ultra, it's a highly competitive market. So I think we're keeping things close to the chest here in terms of exactly how we're going to launch it and what indications. But I can tell you that the development has gone really, really well in terms of the performance we're seeing. We're routinely hitting LOD levels of well below one parts per million.

And in real samples, it's really exciting to see the potential there. I mean that is detecting sort of tumors and early cancer at really unprecedented levels to be able to go that deep. And it's going to be really, I think we're very sensitive to how the products sort of fits with the rest of the portfolio. We want to really make sure that it's sort of seamless in terms of the connectivity between reveal between Guardant360 and between our tissue products. And so we're going to be very thoughtful in terms of how we launch it and which indications we launch it where we believe we can sort of have the sort of greatest traction early on. And then also, I think, focused on thinking about the sort of reimbursement time lines there, the road map, some of the clinical validation as well. So that's a lot of the work we're doing there.

Regarding Shield multicancer, day collection is going very well powered really by the attachment rate that remains very strong. And I mentioned that majority of physician ordering Shield now are opting in to receive the MCD results report. So we are very happy with what they are saying.

Your next question comes from the line of [ Dan Leonard ] with RBC Capital Markets.

So I have a follow-up question on the UnitedHealthcare decision. To the degree that -- AmirAli, to the degree that price sensitivity becomes a topic in that customer base, is there anything you could do to address or help with that, be it co-pays or otherwise? Or is USPSTF really the solution to that? Just how you're thinking about that?

So actually, we have to see what the United conversation would be around like the co-pay and the patient responsibility. So we see how it goes, but obviously, post as we see if there is any co-pay that would go away. And about the rebates, I don't have any comments to share at this time.

Your next question comes from the line of Mason Carrico with Stephens. --

Please ensure you are unmuted locally and proceed with your question. Your next question comes from the line of Evie Koslosky with Goldman Sachs.

So given the acceleration that you saw in therapy monitoring indication for Reveal. Can you walk through some of the cross-selling benefit between therapy monitoring and therapy selection. And then any color you can provide on the sales force productivity related to this?

Well, obviously, it's the same customer base in terms of the same oncologies that are ordering both tests. And bit really sit and in glove in the sense that you -- first test the patients to determine what therapy may be best for them. And then you typically want to see how are they doing in that therapy. And so it's a nice one to punch in terms of how the products fit together. And I think it is not only, I think, sort of a very strong introduction for us in terms of the utility of the product.

You can do some things that I think other products in the field can't do. But I think it also creates a nice sort of data stream for physicians where essentially, you want to see the longitudinal view of every single patient through every line of treatment through every progression. And so it's really, I think, leaning into this platformization concept that -- we talked about a couple of years ago introducing into the field, and this is really, I think, making that vision our reality now.

Your next question comes from the line of [ Page Chamberlain ] with Wolfe Research.

I wanted to ask on the potential impact to volumes for the G360 tissue test after the FDA approval of the liquid test the thought being that reimbursement of the liquid tender NCD might give way to a volume acceleration for the tissue test. So just wondering how you guys are thinking about that and especially in light of the comments that I heard in the prep remark about a phased rollout of the FDA approved version of the test. So can we think about any volume good guys ahead of ALT pricing going into effect.

Yes, it's a great question. I mean, we don't have, I would say, much baked in given the phased rollout, but we certainly are very excited for the potential for that once we get ADLT designation, and we have a sort of more complete rollout of the CDx.

That said, I think we're very excited by the traction we're making with Guardant360 Tissue. It's our second fastest-growing product on the oncology side. We saw acceleration this last quarter. And I think really starting to gain traction as more physicians realize some of the advantages that tissue has. We're seeing a lot of stand-alone volume in the field really is able to process much more challenging samples than a lot of the other tests out there. And that peace of mind, that performance advantage is really sort of standing on its own 2 feet and allowing us to really take a lot of share in the market. Obviously, small numbers still, but very exciting to see the progress this last quarter and for the remainder of theyear.

Your next question comes from the line of Brad Bowers with Mizuho.

Thank you for the question. Actually wanted to hit on profitability. Obviously, a positive FDA data point here lowering the COGS Shield workflow. And I know, overall, we talked about kind of 1 million tests as kind of a break-in number, but the reason I'm asking is the way the street is modeling profitability is that it kind of flips pretty abruptly and severely, which makes sense given a lot of the levers in the business.

But with everything firing off cylinders and expectations kind of for ADLT pricing into next year. I just wanted to hear about how you're thinking about profit, whether there's anything else that's going to be pulled forward or if there's actually some type of EBITDA breakthrough over the next 12 months?

Yes, I can answer that. And really, when we're looking at sort of well, adjusted EBITDA and profitability, we almost talk about that in a similar breadth to free cash flow burn. And we've been very sort of clear that getting to profitability, getting to cash flow breakeven, it's a key focus for the company. We're well on track to get to cash flow breakeven by the end of 2027.

And if you look at the business, excluding screening, actually, that business now is adjusted EBITDA positive. It's generating positive cash flow. And so we've achieved that with the rest of the business. We're continuing to make heavy investments to build out the commercial infrastructure on screening. And that's going to continue throughout as we continue to ramp up. We do expect at a point in '27 that we will reach some sort of critical mass in our commercial lending and we'll start to get a lot of leverage as the screening gross profit continues to increase, and this reduction in the Shield cost per test is going to help us get there.

And we should start to see screening start to ramp down in the burn sometime in '27. And that business itself getting to breakeven in 2028. So we're well on track with what our expectations were. We're very focused on getting to profitability and case. What could bring that forward? I think in the previous answer, we talked about getting ADLT designation for Guardant360 with an increase in the Medicare price and potential increase in Guardant360 ASP. If and when that happens, obviously, that's going to again generate incremental bottom line cash and profit for us.

And so that could accelerate into that breakeven and it could accelerate our sort of profitability ramp following that. So again, I think we're tracking very nicely to our expectations.

Your next question comes from the line of Tycho Peterson with Jefferies.

This is Noah on for Tycho. Congrats on the quarter. I wanted to ask about Guardant360 tissue. You're clearly outgrowing the broader market in this application. Curious if you think these share gains are tied to maybe some of these current testing trends of liquid that you've been talking about or an actual shift in provider preference. And then what does the underlying assumption look like for growth in this market on a go forward?

Yes. No, I think right now, I think a lot of the growth is really sort of tissue standing on its own two feet. It's a product that can essentially utilize much smaller tissue samples and a lot of the tests that are out there that I think there's a lot of the sort of initial traction that we see with that product. But it's also one that is really one of the most comprehensive products in the market in a very large genomic panel, genome-wide mutation. Full -- it's now a whole transcriptome as well. And so it's really one of the most comprehensive offerings on the market. We also recently rolled out a lot of the apps that we had in our liquid side on the tissue side as well.

And so it's really benefiting from Infinity AI, the platform that we have in terms of developing a lot of these differentiating clinical applications. And so obviously, it bodes well for that franchise in the future as concurrent testing does become more and more prevalent and more and more of the standard of care for many tumor types.

Our final question comes from Catherine Schulte with Baird.

Maybe on Reveal. Can you just talk through expectations on when you might hear back from MolDx on some of these indications, some of them are hitting close to the earmark. And then on the lower COGS version of Shield, we look at that PMA supplement, it looks like it kind of streamlines it to a methylation-only workflow and removing fragmentomics and the somatic component. So can you just talk through the development work that went into that and kind of how that might inform future iterations of the test?

Yes. In terms of reveal, I mean, I can say that I think we're making progress on the submissions and the packages we have there. I mean, certainly, I/O and breast are probably the closest to the finish line. I think we're hopeful that we can get at least one or both of them by end of this year. And obviously making some good progress in chemo as well.

Obviously, it's taking a little bit longer than we would have liked, but I think we're very confident that we can get these over the finish line. And we have a number of other submissions that sort of are under development and in preparation. As soon as those get -- as soon as the associated manuscripts get published, we'll be submitting those as well. So we have a lot of sort of balls in the air in terms of reveal, and we know that it's going to be a very, very big sort of franchise for us going forward as soon as we get some of these reimbursement wins.

Regarding the Shield workflow improvement, yes, actually, we are -- we focused it on methylation only, which the information is in the current version of Shield V1. The algorithm updates and multimodal Shield are generating kind of exciting pipeline activities for us in terms of hopefully continuing to see improvement in the Shield performance.

This concludes today's call. Thank you for attending. You may now disconnect.

I'm on the Bank of America Life Science Tools and Diagnostics team. And for our next chat, we're excited to host Guardant Health. We're joined by Co-Chief Executive Officer, Helmy Eltoukhy; and Mike Bell, Chief Financial Officer.

Helmy, Mike, thank you so much for being here. Really appreciate you taking the time. Yes. Great to be here.

[Operator Instructions]

Maybe we'll start with a high-level question. You guys just reported first quarter just a couple of days ago, really strong broad-based nice raise.

Talk through how the quarter played out to your expectations and where things came a little bit better and how you're thinking that going forward?

Yes. I mean I think it's been exciting to see us sort of lean into the [indiscernible] that we're embarking on in terms of utilization adoption [indiscernible] doing really well and that I think the smart platform is a gift that keeps on giving and [indiscernible]. There's a thing in diagnostic therapeutics, how you start having strong first quarter [indiscernible] MRD.

I think it does [indiscernible] obviously are pushing longitudinal testing, pushing in the indications we're in and had a very strong start [indiscernible] And we're very excited about where that is going up to [indiscernible] impressive given, [indiscernible] [Technical Difficulty]

Maybe we'll just build on that in terms of taking that into the full year guide raise. You raised the guide by more than you beat. You updated some of your assumptions for oncology for Shield. Sort of what gives you confidence in that momentum continuing?

And sort of maybe you could deconvolute the guide raise, like what are the biggest drivers of that, Mike?

Yes. I think yes, we're really pleased with the Q1 performance. It enabled us to raise our guide for the full year. There's 2 key drivers of that guide raise. One is oncology volume. And secondly, it's Shield volume.

And so on the oncology volume, Really, the key though, is Guardant360 and really the strength that we see, and I think Amy was talking about it with the [ SMA ] platform. We started Q1 very strongly.

And I think, again, it just gives us a lot of confidence going into the rest of the year. We know we've got additional catalysts with new waves of smart apps through the year. And then on the -- specifically on the Reveal side, again, we saw good traction with MRD, but we were very pleased with how therapy monitoring is tracking. We launched that in Q4.

It was incredibly strong in Q1. And so again, I think the strength that we saw just enabled us to have a lot of confidence for the remainder of the year. And then with Shield, we talked about the momentum in March. We see a lot of catalysts starting to come into play. So we're seeing better rep productivity. We're adding to the number of reps we have.

And so throughout the year, we expect that additional number and the increased productivity to drive continued volume growth. We initiated our Quest collaboration towards the end of Q1. That's still early days, but the signs were very, very positive. And so we think that's going to be a contributor for the remainder of the year. And as well as having a strong [ HPC ] marketing campaign.

Last year, we added to that in Q1 with a lot of DTC initiatives. Again, that's very early days, but the initial response that we're getting for that, again, looks very strong, and we're continuing that DTC campaign into Q2.

So I think we see a lot of catalysts on the screening side. And again, that gave us a lot of confidence to increase our volume guidance. And of course, the volumes driving for those products are driving the revenue increase.

Maybe sticking on screening and Shield. You raised your both volume and revenue assumptions for the year. Kind of if you just do the math real quick, you kind of talked to maybe 10,000 tests sequential quarter-over-quarter through the year. As you talked about Quest in the second half, sales rep productivity, are those the big pieces driving that?

Is that more of a second half dynamic? Sort of like is there upside to that 10,000 per quarter jump to sort of like a degree of conservatism that? And what are the key drivers of that step-up?

Well, I would say that, that sort of on average, 10,000 a quarter. We're very confident with that quarterly cadence. We've got a lot of experience now from the prior year, and we know how sort of the seasonality works.

So that gives us confidence. And again, probably the key driver at the moment of the volume growth is on the sales rep side as it has been for the last sort of 12, 18 months as we're adding new reps and those tenured reps are starting to get more and more better and better productivity.

So they'll continue to drive in the near term. And I think, yes, we would look at the impact of Quest really starting to kick in the second half. And similarly, with the DTC, I think that will start to really kick in on the second half.

On top of that, and we've talked about this a lot, but we're expecting ACS guidelines to come in the relatively near future. That's not in our guide at the moment for 2026.

But if and when that comes, we see that, that can be a positive upside. Initially on the volume side, it will enable us in those ACS states to open up to patients under 65 and drive more of the commercial volume. We see that the revenue impact of that coming more into '27 because it will take time for the commercial payers to come on board and start paying us.

But again, we see that as being a potential upside to our guidance for the back half of the year.

Okay. All right. Maybe on the topic of ACS and reimbursement or ASPs. You came in a little bit higher in the quarter for Shield than you expected, and you're projecting something like [ 775 ] for the rest of the year, which is relatively consistent with where you were before, but there was a little bit of a catch-up dynamic there.

Can you talk about how that played out in the quarter and just sort of the mix component for Shield and how that into the guide?

Yes. I mean, since launch, we've had this real focus on reimbursable tests, so the Medicare age population where we're getting paid $1,495 Medicare fee-for-service with the ADLT rate, and we're getting very good payments from Medicare Advantage payers.

That actually keeps continuing to get better and better. That's what drove the out-of-period true-up that we had for screening in Q1 and also in Q3 and Q4 of last year. So that's going incredibly well. As we open up with Quest, as we've got the DTC campaigns going and then potentially as ACS kicks in, we're expecting to see more and more volume come from the under 65s.

And we've put a lot of friction in the system previously to sort of prevent that, but I think we'll just relax that. And so our expectation on ASP is initially, that's going to tick down the ASP because we'll get more commercial zeros initially.

But effectively, we're opening that up because we're expecting, particularly with ACS guidelines to start getting better and better commercial payments. So it will be an initial tick down, but over time, it's going to ramp back up as the commercial payers start to pay us.

Do you have a sense of the timing on that in terms of how long it ramps back up? Is it really dependent on ACS? Or is there -- do you see like a 12-, 24-month gap? Or just sort of walk us through the bridge back up?

Yes. Some of it obviously is going to depend on the timing of ACS guidelines. But I think we think probably it will take around 12 months to really get to a position where we want to be with commercial payers. There's probably going to be some payers that early on start to pay us, but we're fully expecting it will take time. We've got a very strong team, reimbursement team that has got good relationships with pretty much all of the key payers, and we've built that up over time from the oncology side of the business.

So once we get into guidelines, I think that team will go into full effect, and we'll be having a lot of dialogue with those payers. And 12 months is our sort of expectation, but hopefully, we'll be trying to sort of bring that forward as quickly as we can.

Okay. All right. Let's chat a little bit about therapy selection. Helmy, in your opening comments, you made an interesting point, perception of maturity in that business. I mean that's certainly been a talking point for a while, but you think you put up really impressive numbers there, 30% volume growth despite growing competitive noise, really strong growth both in Liquid and Tissue.

Sort of what's driving that sustained strong performance? You continue to sort of push out that narrative of maturation or saturation in the business?

Yes. I think it's a testament to what we said in our Investor Day that we'd rather -- we'd much rather be sitting where we're sitting as the leader in Liquid biopsy sort of therapy selection rather than on the Tissue side just because we think the market has so much more room to grow.

When you think about patients living longer, like every patient progression that's there, different lines of therapy, the guidelines and clinical practice really requires essentially doing another genomic profiling at each progression since the cancer is changing.

And frankly, that is not standard practice right now. I think very few patients are getting tested multiple times. And that's something that I think is a huge catalyst and a huge driver of, frankly, pretty significant growth multiples over where the market is today. Secondly, still a lot of patients aren't getting even an initial comprehensive profiling, especially on the Liquid side.

And so I think that's where I think you see outsized growth there as well. And so I think it's what's exciting is that a lot of the growth we're seeing is really, I think, predicated on the -- what we believe to be superior product market fit we have with this new smart platform and the fact that we're seeing sort of share gains as a result of that as well as we seem to be sort of sucking up more than our fair share of market growth as well, at least on that initial time point, that sort of 0 to 1 moment.

And that bodes well for us continuing to lean in on moving the market from 1 to sort of end number of tests per patient. And yes, it's been exciting. And the pieces are all coming together. You can think of the tip of the spear is Guardant360 Liquid for us in the smart platform. But that sort of brings along our Tissue platform. It brings Reveal for therapy monitoring along for the ride and creates this really nice flywheel and synergistic effect between these products.

You mentioned share gains. Is that across the board? I mean, obviously, Tissue is still really, really early in terms of ramp. How much are you seeing the -- like you just discussed, having being able to leverage both?

Yes. I would say, speaking more for Liquid, I think Tissue is still probably too small. It's probably in the weeds in terms of exactly where that's coming from. But we're excited for really this next chapter as we get FDA approval for Guardant360 Liquid as we continue to lean into therapy monitoring more, we feel it's going to be increasingly harder to use multiple sort of providers for something that you'd rather see a holistic and unified view of with each and every patient.

Okay. I mean you touched on therapy monitoring, so let's go there. Is that starting to matter? Is that starting to show up in numbers? I mean it's still very early, but you seem to be having really good traction there. So can you talk about what you're seeing there?

Yes. We're just one full quarter now in terms of the launch of therapy monitoring. It's -- we think it's going to be a pretty large indication in general when you think about 1 million-plus cancer patients under sort of a late-stage therapy.

Each of those patients sort of needing to be monitored, needing to be potentially switched to another therapy. We think it's a really nice sort of prompt for leaning into progression testing as well. If you see a number that you're following for that patient, you see ctDNA levels going up, then it's pretty clear that patient needs to be tested for new mutations for potentially new therapeutic options.

And so we think the sort of the sum is greater than sort of the individual parts there in the sense that like these tests really work together really nicely.

You talked a lot about on the quarter and your last couple -- last couple of quarters about smart apps and the contribution there and the benefit you're seeing for the platform. It seems that that's having a bigger and bigger impact over time.

Just talk about the uplift you're seeing there and where you think that trajectory could take you?

Yes. Ever since we launched the Smart platform in 2024, we've seen just kind of a steady sort of accelerated growth rate for 360 Liquid, and that continues to this day, and we see that continuing, I think, into '26 and beyond.

And the nice thing about the platform is that we're continually amazed by the capabilities that are unlocked by not just having this differentiated chemistry but by then, the data that we're accruing as we have hundreds of thousands of samples, well more than 500,000 methylation profiles.

As we use more and more data to train some of these new algorithms, the resolution we can see, some of the performance capabilities we can see continue to grow quite exponentially. And so we're very confident. We have dozens of new applications under development. And even just this weekend, the team was e-mailing me with like new applications that we didn't think were possible that suddenly are working now.

And obviously, this is being accelerated with some of the Agentic AI capabilities and our ability to sort of increase the velocity of exploration we can do with multiple agents looking at sort of like different analyses. And so it's a great time. I think our thesis that he or she who has the most sort of biological data will eventually run out is playing out. We've been sort of heads down focused on building the sort of data acquisition engines in 360 and Reveal and Shield.

And now with like the whole AI revolution, it's made our ability to sort of take all of that data and analyze it in a streamlined and very cost-efficient way, all the more powerful.

Are you -- I mean let's stick on that topic. Are you leveraging that today already? Is that starting to manifest already? Is that sort of a future trajectory?

In terms of AI?

Yes.

Yes. I mean it's been transformational for the company. I mean there's a huge shift from -- obviously, we are always tech forward coming from engineering space and so on and from Silicon Valley, but really pushing to really rebuild the stack in a sort of AI native fashion across the different divisions in the company from legal to HR to operations to obviously, like our software, I think something like 50% of our software is written by AI now and produced and this has been the case for many quarters and for over a year now.

You think about like just the logistical burdens, administrative burdens that are required in the health care space around billing, reimbursement and appeals and the level of automation we have now has been really fascinating and really exciting. Same thing on the regulatory side, being able to put together regulatory submissions much more quickly, making sure you double and triple check that with consistency and coherency that can be sort of aided by AI. I think, has been really transformative in terms of the velocity by which we can move across these different divisions.

And then on the R&D side, the informatics work, our 10x engineers have become 100x engineers, frankly. And the fact that you have individuals who are really good at algorithmic development, but maybe didn't have the bandwidth to sort of harden the software or build like very hardcore kind of software deployments can do that now like very easily through Agentic fashion, I think, has given a number of individuals, frankly, unforeseen superpowers in terms of being able to move much more quickly.

Okay. I mean, so far, I think we've touched on a lot of the positives from the quarter in recent times. Let's just run through some of the -- a little bit more negative data points real quick. I mean one is the SERENA-6 AdCom. It was a lot of focus in the quarter, maybe a little bit too much of a focus.

Now that you've moved past and we had a little bit of time to digest it, just what do you think are the more practical implications, both near term for SERENA-6 specifically, but also for future opportunities on the same vein.

Yes. So I think the silver lining there was that I think to every single person on the committee there was, I think, supportive and believe that ctDNA testing was the future of oncology. So I think sort of the North Star is still alive and well, I think, despite the mixed decision there.

I think you had a number of the sort of key KOLs there also very supportive of this sort of new paradigm, which I think was great to see. And then I think [ 306 ] was never really the primary sort of avenue to get to this sort of modality of longitudinal testing and adaptive managing, imagine the disease, it was really reveal for therapy monitoring is our sort of #1 sort of plan of attack of making that new vision, that new reality of standard of care.

And I think we're off to a really good start. Obviously, we have some submissions for reimbursement in flight with IO and chemo, and we'll have a number of other ones as we accrue more data. And so yes, I think regardless of how camizestrant sort of turns out, we think this is a future that is very much in the near term and one that we can make happen like just within the capabilities we have within our own company.

Okay. Another topic during the quarter that got a lot of attention was crush more broadly, I think across the entire diagnostic universe, not necessarily as much on Guardant, but certainly spill over into that as well. Where do you sit on that debate? And why do you think you're insulated and not necessarily impacted by that?

Yes. I think there's a lot of, I think, confusion around that. I think from what we see that was a discussion of sort of different practices of some of the different MACs in terms of how they adjudicate claims.

And I think MolDX has sort of been proactive in that discussion in terms of some of the positive assessments that are required, technical assessments and submissions, positive LCDs and so on.

Obviously, we're squarely within that MAC. And so we actually think we're less sort of affected than most. And then the other piece is most of our products are essentially going to national CMS. So we're sort of above the fray, I would say, to some extent.

Shield, obviously, has a national coverage decision. Guardant360 CDx does soon Guardant360 Liquid will too as we get through FDA approval.

So we're -- I think there was confusion around that and ADLT and so on. And this is really something that is a very different conversation than anything around PAMA, which is really in the realm of sort of legislative action, and we don't think is under any kind of risk at this point.

Okay. And the last one that we had some questions on immediately post the result was you had a little bit of an update in the 10-Q about civil investigation in Florida.

It doesn't seem to be a huge concern. Just talk us through why you're not necessarily worried about that. So maybe any background you can give there?

Yes. I think in this industry, it's one of the -- we look at this as sort of normal course of business. I think these come every now and again. I think a lot of our peers, you'll see have had those sort of CIDs over the last few years.

We had one back in 2022 list of questions, which we answered. Nothing came of it. We take these things, of course, very seriously. And of course, we'll work with them and respond accordingly. And suffice to say, we have a very strong compliance program across Guardant that we're actually very proud of.

And so based on that, we don't look at this as an issue. Again, we'll take it seriously, but we don't see it as material or a specific issue for us to deal with.

Okay. Maybe in the last couple of minutes left, I want to ask a couple of sort of big picture thematic ones. Kind of debate that emerged during dinner last night that I thought was really interesting was sort of the -- where diagnostics fits and especially cancer care continuum diagnostic fits in therapeutics in the world today. You've been fighting this fight for more than a decade now.

And it's sort of this question of value of diagnostics versus a therapeutic. You made an interesting point earlier. You talked about [indiscernible] you talked about increasingly people do view ctDNA as the future of oncology, and there is a paradigm shift. Sort of where are we on that curve? And is that -- is the progression along that curve of the understanding of the importance of diagnostics, is that at the end of the day, what's underpinning the strong growth you're seeing in oncology? Is that conversion of that paradigm shift really what we're seeing play out now?

Yes. Look, I think diagnostic companies for probably decades have been saying that they're not getting the true value they deserve that they inform decisions, there should be more value there.

And the reality is that 70% of clinical decisions are informed by diagnostic testing today. So they are essentially the lion's share of how physicians make decisions on patients. And when you think about the sort of wallet share across the board, and people sort of ring their hands around diagnostic testing.

Frankly, all of Medicare diagnostic testing is $8.3 billion compared to $1.7 trillion, $1.8 trillion in terms of total Medicare and Medicaid spend. And so we're sort of stepping over dollars to grab pennies when we think about like optimizing the price of diagnostic testing when we have these massive boulders of costs when you think about the $100,000 cost of therapeutics that are out there, $1 million cost of therapeutics.

Any other industry, you measure twice and cut once. For some reason, we think we want to save like a little bit of money, a couple of thousand dollars to then misutilize $100,000 drugs. And so I think we just have to take a step back and look at the totality of the picture. And I think it will happen. There's just no industry where data is not king.

I mean, financial industry, tech industry, everywhere. And I think historically, diagnostics have been pretty simple. We've been sort of very unidimensional in terms of the type of data that you're getting out of them. When you have these broad tests where the potential utility of the test is way greater than its current utility, that's where I think you get these like big step shifts in industries. And that's what's starting to happen now.

And especially in our industry, I think, is the one that's leading the charge here. I mean we're going to have 1 exabyte of beta very soon, like in our portfolio. And there's just this nice sort of snowball effect in terms of like greater and greater utility that we can sort of glean and provide to physicians.

So we're very much, I think, on sort of our way to, I think, correctly shifting the value proposition towards diagnostics.

Mike, maybe one for you. You continue to make strong progress on gross margins. You've got some nice operating leverage and volume leverage as you're moving through the year. But at the same time, you're still making a lot of investments in commercial sales force and continue to invest in R&D.

Just talk about the balancing opportunities there of investments versus margin expansion as you go towards EBITDA breakeven, free cash flow positive.

Yes. At the moment, we're sort of balancing that by taking screening separately and then we take the rest of the business. If you take the rest of the business from sort of middle of last year, that was free cash flow positive and adjusted EBITDA positive.

And for the full year this year, it's going to be -- going to continue to be so. In fact, very -- quite strong adjusted EBITDA and cash flow in 2026. And so I think we're getting the balance right of reinvesting in the right areas of R&D and sales and marketing of course the oncology and biopharma business because we still want to support innovation, and we still want to support top line growth.

So I think we're making the right sort of balance there. On the screening side, this year, same as last year, we're investing heavily on the commercial build-out. We want to take as much advantage of this first-mover position that we have.

We want to ramp up the sales field team as quickly as possible. And so that's what we're doing. And so we're reinvesting every sort of dollar of incremental gross profit back into the sales and marketing line. And that's going to continue until we get to a certain level of scale. And then we're very confident in 2027 on the screening side, we'll reach an inflection point where we've got to that scale on the commercial build-out.

And so incremental gross profit as we're deriving that then can start to drop down to the bottom line. So we're still -- even with these heavy investments across screening, we're still committed to being breakeven by the end of '27 and very confident we'll do that.

All right. Maybe just quick closing remarks. Helmy, anything specific you want to call out? I mean, again, really good progress, really good start to the year, but just sort of conclude thoughts or what you'd like to leave investors with?

Yes. No, I think it's -- I think the numbers speak for themselves. Very strong quarter. Everything is sort of firing on all cylinders. And yes, I think it bodes well for this sort of next chapter of Guardant's growth.

All right. Well, thank you...

Thank you very much.

Thanks, Helmy, Michael.

Thank you for being here...

Thanks, everyone.

Good afternoon. Thank you for attending the Guardant Health Q1 2026 Earnings Call. My name is Matt, and I'll be the moderator for today's call. [Operator Instructions]

I'd now like to pass the conference over to our host, Zarak Khurshid, VP of Investor Relations. Zarak, please go ahead.

Thank you. Earlier today, Guardant Health released financial results for the quarter ended March 31, 2026. Joining me today from Guardant are Helmy Eltoukhy, Co-CEO; AmirAli Talasaz, Co-CEO; and Mike Bell, Chief Financial Officer.

Before we begin, I'd like to remind you that during this call we will make forward-looking statements within the meaning of federal securities laws. These statements involve material risks and uncertainties that could cause actual results or events to materially differ from those anticipated. This call will also include a discussion of non-GAAP financial measures, which are adjusted to exclude certain specified items. Additional information regarding material risks and uncertainties as well as the non-GAAP financial reconciliation to most directly comparable GAAP financial measures are available in the press release Guardant issued today as well as in our 10-Q and other filings with the SEC. Guardant disclaims any intention or obligation to update or revise financial projections and forward-looking statements, whether because of new information, future events or otherwise, except as required by law. The information in this conference call is accurate only as of the live broadcast.

With that, I would like to turn the call over to Helmy.

Thanks, Zarak. Good afternoon, and thank you for joining our First Quarter 2026 Earnings Call. Starting on Slide 3, we entered 2026 with significant momentum that accelerated through Q1, driving a remarkable quarter for Guardant Health. These results validate our strategic vision of delivering increasingly more actionable insights to physicians and patients across the care continuum. Notably, our commercial flywheel has achieved a new level of velocity, delivering our fastest year-over-year percentage revenue growth in the last 5 years and surpassing the $1 billion trailing 12-month revenue milestone. This is a testament to the burgeoning scale and long-term durability of our business.

Before I share our results in more detail, I'd like to share a story that illustrates the real-world impact of our tests. A 77-year-old Atlanta resident recently completed a Shield CRC test. The results came back positive and the patient underwent a diagnostic colonoscopy during which a lesion was discovered and biopsied. The lesion was subsequently confirmed to be malignant by pathology. The patient then underwent surgical resection of the malignant lesion, which was confirmed to be highly localized. The patient welcomed this news from her oncologist and was further relieved that no additional treatment was necessary. Patient outcomes like this are one of the many reasons we have benefited from accelerating adoption and growth.

Turning to our revenue performance on Slide 4. We had a phenomenal start to 2026, delivering $302 million of revenue in Q1, representing 48% year-over-year growth. The growth was strong and broad-based across our Oncology, Biopharma & Data and Screening business lines.

Taking a closer look at our oncology business on Slide 5. Oncology revenue growth accelerated to 36% year-over-year, driving Q1 revenue of $205 million. Oncology test volumes rose 47% to approximately 86,000 tests, up from 59,000 in the prior year period. This was the highest year-over-year percentage growth on oncology volume we've seen in nearly 3 years with strength across all products. We're excited to see the expanding role of our portfolio across the cancer care continuum.

Turning to Slide 6. Our 47% year-over-year volume growth reflects the increasing breadth of our portfolio across both therapy selection and MRD. Guardant360 Liquid delivered 30% volume growth year-over-year, while Guardant360 Tissue was our second fastest-growing product. Smart platform innovation continues to translate directly into volume growth for both products with InfinityAI powering a steady cadence of new clinical applications that are driving deeper adoption among oncologists. We have a strong pipeline of additional smart apps in development, and we look forward to continuing that cadence.

Reveal remained our fastest-growing product with volumes up over 100% year-over-year, reflecting strong adoption of Reveal in MRD across indications and enthusiasm for our new therapy response monitoring use case among our customers in its first full quarter post launch.

Moving on to Slide 7. With each patient tested, our data treasury continues to deepen and diversify. Our data repository harnesses insights from over 1 million patient samples, 500,000 epigenetic profiles across more than 100 tumor types, and each new sample helps compound the breadth and uniqueness of what we can deliver over time. By applying our InfinityAI learning engine to this expanding data moat, we uncover novel biological signatures, power new smart app development and accelerate therapeutic discovery for our biopharma partners. The result is a compounding flywheel wherein data drives better insights, which, in turn, fuels volume growth and strengthens our data advantage.

Turning to Slide 8 to take a closer look at our Reveal data pipeline. We continue to make strong progress in generating and publishing compelling data across multiple cancer types and indications. We have submitted data packages to MolDx to support coverage in breast cancer surveillance, immuno-oncology monitoring and chemotherapy monitoring, and we are engaging constructively with MolDx through the Reveal process. Each submission represents a potentially meaningful reimbursement catalyst, and we are excited about the ASP upside that favorable outcomes would unlock. We are also advancing our work towards the MolDx submission for CDK4/6 inhibitor monitoring. Looking further ahead, we have ongoing studies across more than 5 additional tumor types in both the adjuvant and surveillance settings. The breadth of this pipeline gives us real confidence in Reveal's trajectory and its expanding role across the cancer care continuum.

Turning to Slide 9, we continue to make strong progress across the Guardant360 portfolio on multiple fronts. For Guardant360 Liquid, our FDA review remains on track. When approved, Guardant360 Liquid will become the most comprehensive FDA-approved liquid biopsy for therapy selection on the market. Moreover, this development will help simplify ordering across our therapy selection portfolio and create better connectivity across our larger testing ecosystem.

On the Tissue side, we are excited to announce our second major platform upgrade in less than a year, expanding RNA testing to whole transcriptome. This further builds on the genomic and epigenomic foundation of our Smart platform, and we believe reinforces Guardant360 Tissue's position as best-in-class in the tissue CGP market. We expect these upgrades to be a meaningful volume catalyst for both Liquid and Tissue, particularly as it opens the door to converting current nonusers.

Turning to Slide 10. Guardant had another strong showing at AACR this year. Together with our independent collaborators, 38 abstracts were presented spanning our entire oncology portfolio. The depth of the Smart App data was remarkable. 25 of the abstracts featured InfinityAI generated findings, which speaks to how rapidly this platform is maturing. We were particularly encouraged to see concrete evidence of InfinityAI enabling therapeutic response prediction and improving detection of clinically challenging alterations like ALK-fusions and MTAP deletions. These are exactly the kind of insights unlocked by our data treasury and epigenomic capabilities that truly differentiate our platform.

Shifting gears to our Biopharma & Data business on Slide 11. We delivered another strong quarter with revenue growing 17% year-over-year to $53 million. The last few months have been highly productive with respect to our CDx strategy, which included Guardant360 CDx FDA approval for Pfizer's Braftovi in BRAF V600E-mutant metastatic colorectal cancer and this week's CDx FDA approval with Arvinas and Pfizer's VEPPANU for ER-positive, HER2-negative, ESR1-mutated advanced breast cancer. Our CDx franchise now spans 26 approvals across the U.S., Japan and Europe, backed by a robust pipeline across multiple partnerships with leading biopharma companies.

In the quarter, real-world evidence generated from InfinityAI as supplemental data alongside clinical findings contributed to the first tumor-agnostic approval of Daiichi Sankyo's ENHERTU in Japan. We also saw further strengthening of our relationships with leading biopharma companies, including a multiyear agreement with Merck to develop companion diagnostics and commercialize novel therapies as well as last week's announced collaboration with Nuvalent to develop companion diagnostics with an initial focus on Guardant360 Tissue. Together, these developments reflect the growing strategic value of our smart platform and InfinityAI to leading biopharma companies and reinforce our confidence in sustained growth in this business.

With that, I'll now turn the call over to AmirAli for an update on screening.

Thanks, Helmy. Moving on to Slide 12. Q1 was another strong quarter for Shield. We delivered $42 million of Shield testing revenue driven by approximately 44,000 tests compared to $6 million revenue and approximately 9,000 tests in Q1 of 2025. Revenue growth has closely tracked volume growth, reflecting favorable collections and a disciplined focus on reimbursable lives. Now roughly 18 months into the commercial launch, we continue to break records and look forward to sustained strong growth throughout the remainder of 2026.

Moving to Slide 13 for a closer look at Q1 screening highlights. We saw strong volume throughout the quarter and exited the quarter with accelerated momentum in March, which gives us real confidence in our trajectory for the remainder of the year. Our growth was fueled by continued improvement in sales rep productivity and amplified by a series of marketing initiatives that came together in the quarter.

We launched our DTC and influencer campaigns in conjunction with colorectal cancer awareness month, including our national campaign with Patrick Dempsey, which I will cover on the next slide. Our Quest collaboration launched nationwide in late Q1, and we are pleased with the early signals. Quest is already opening doors for us in health systems and physician practices where we did not previously have a strong direct presence. Shield continues to demonstrate a high adherence rate of over 90%, which is one of the key differentiators of Shield versus other noninvasive modalities. Finally, we launched Shield Multi-Cancer Detection in Asia through our partnership with Manulife, extending our reach into an important new market segment.

Taking a closer look at our direct-to-consumer programs on Slide 14. Q1 marked our first comprehensive DTC campaign spanning TV, digital and influencer channels and the results exceeded our expectations. Together, these efforts generated over 1 billion impressions. The centerpiece was our partnership with Patrick Dempsey, actor and a cancer advocate, who shared his personal experience using Shield during colorectal cancer awareness month. We saw a meaningful step-up in consumer engagement, including website traffics and consumer-initiated provider engagements, which we expect to translate into greater adoption of Shield.

Turning to Slide 15. Complementing our DTC program, we have expanded our healthcare provider marketing initiatives, which drove record HCP engagement in Q1. Our March campaign featured targeted messaging to about 200,000 HCPs emphasizing that many millions of Americans remain unscreened, and that Shield is the only FDA-approved blood test for CRC screening with Medicare coverage.

Also, we continue to make great progress to enhance physician and patient experience. We are rapidly expanding the number of accounts with direct integration into their Epic eClinicalWorks and Athenahealth EMR systems. Moreover, we officially launched our collaboration with Quest Diagnostics nationwide in late Q1, which has fast tracked our EMR connectivity to more than 650,000 HCPs. We expect this to meaningfully increase depth of ordering among connected physicians. Quest national sales team has now started actively promoting Shield. While still early days, we are pleased with positive contributions we are seeing.

Finally, our patient navigation team is actively helping practices connect patients to convenient phlebotomy access, utilizing our nationwide network of 40,000 phlebotomists as well as Quest 8,000 patient service centers.

Turning to Slide 16. At Guardant Health, we are dedicated to continuous improvement of our products and patient experience. We are excited to report that we recently received FDA approval to reduce the amount of blood collected from patients to process Shield test to 2-tubes from the original 4-tube kit. We applaud the FDA for their continuous collaboration and dedication to strong patient outcomes.

Moving to Slide 17. Our goal has always been to detect many cancer types early when they are most treatable. With that in mind, we developed Shield as a Multi-Cancer Detection platform. When a physician orders Shield for CRC screening, they can opt in to receive multi-cancer detection results report. The Shield MCD report is available to Shield CRC patients who authorized the release of their medical records to Guardant. The launch of this initiative establishes a scalable platform for clinical data generation, enables assessment of the utilization of MCD results in patient care and provides a new avenue to expand patient access to Multi-Cancer Detection.

The MCD report covers finding across 9 additional cancer types behind CRC, including lung, breast, ovarian, pancreatic and others. We are encouraged by HCP and patient response to this data collection initiatives and the strong opt-in that we are seeing. As a result, we believe we are building what will quickly become the largest clinical database of Multi-Cancer Detection outcomes from patients in the United States.

Now on to Slide 18. During Q1, we announced the expansion of Shield multi-cancer detection in Asia through our partnership with Manulife. Manulife serves more than 13 million customers across Asia. We initially launched in 3 key markets: Hong Kong, the Philippines and Singapore. This is a differentiated go-to-market strategy, which leverages a direct channel to a large member base within those markets.

With that, I will now turn the call over to Mike for more detail on our financials.

Thanks, AmirAli. Moving to Slide 19, I'll now review our first quarter 2026 financial results. Unless otherwise noted, all growth rates are year-over-year.

Total revenue in Q1 increased 48% to $302 million, reflecting strong growth and continued momentum across Oncology, Biopharma & Data and Screening. Starting with Oncology. Revenue increased 36% to $205 million. We reported approximately 86,000 oncology tests in the quarter, representing 47% volume growth with broad-based strength across the portfolio. Guardant360 Liquid volumes grew 30%, supported by expanding clinical utility and continued traction of our Smart Apps. Guardant360 Tissue also continued to scale and remains our second fastest-growing oncology product. Reveal remains our fastest-growing oncology product with volume growth exceeding 100%, reflecting strong adoption in MRD and continued expansion in therapy response monitoring following its Q4 2025 launch.

Average selling prices were stable sequentially with Guardant360 Liquid in the range of $3,000 to $3,100, Guardant360 Tissue above $2,000, and Reveal between $600 and $700. As a reminder, we've submitted data packages to MolDx for medicare reimbursement covering breast MRD and both immunotherapy and chemotherapy response monitoring. Favorable outcomes from these submissions will provide upside to Reveal ASP.

Biopharma & Data revenue was $53 million, up 17%, reflecting sustained demand and continued strength across sample testing, companion diagnostic projects and data products.

In Screening, Q1 revenue was $42 million compared to $6 million in the prior year period. The increase was primarily driven by approximately 44,000 Shield tests in the quarter compared to approximately 9,000 in the prior year period. Volume tracked in line with expectations through January and February. And following the launch of our Quest partnership and successful HCP and DTC programs during colorectal cancer awareness month, we saw clear momentum build through March and exited the quarter strongly.

Shield ASPs increased significantly year-over-year, reflecting the Medicare rate step-up from $920 to $1,495 that went into effect on April 1, 2025, following Shield's ADLT designation. As a reminder, after the initial 9-month period of list price-based reimbursement, Shield transitioned to market-based pricing at the start of 2026. Based on Commercial and Medicare Advantage payments received in 2025, the $1,495 Medicare fee-for-service rate is now established for 2026 and 2027. Out-of-period revenue in Q1 was broadly consistent with quarterly trends over the past year and totaled $22 million, which consisted of $18 million Oncology revenue and $4 million Screening revenue.

Turning to Slide 20. Non-GAAP gross margin was 66% in Q1 2026, up from 65% in the prior year period. The improvement was primarily driven by lower Guardant360 Liquid cost per test reflecting the ongoing transition to NovaSeq X, which will be completed in May 2026. The transition reduced Guardant360 Liquid sequencing cost per test by nearly $200 versus Q1 2025. We also benefited from improved screening gross margins, which I'll discuss on the next slide.

Non-GAAP operating expenses were $268 million, an increase of 34%, primarily driven by commercial investment. While R&D and G&A saw modest year-over-year increases, sales and marketing expense rose to $154 million in Q1 2026 compared to $94 million in the prior year period. This reflects continued investment in building out our screening sales infrastructure, advancing Shield HCP and DTC marketing programs and supporting ongoing oncology revenue growth.

Adjusted EBITDA loss in Q1 was $59 million compared to a loss of $59 million in the first quarter of 2025. Free cash flow burn in Q1 2026 was $71 million compared to $67 million in the prior year period. The year-over-year change reflects an increase in the company-wide annual bonus payout in Q1 2026 compared to Q1 2025. Excluding this impact, free cash flow burn decreased by approximately $12 million year-over-year. We remain focused on disciplined cash management and are on track to decrease full year 2026 free cash flow burn compared to 2025. We ended the quarter with approximately $1.2 billion in cash and investments.

Turning to Slide 21. Over the past year, Screening non-GAAP gross margin improved from 18% in Q1 2025 to 56% in Q1 2026. This improvement has been driven by an increase in Shield ASP, as I outlined earlier, and a decrease in Shield non-GAAP cost per test from $520 in Q1 2025 to $420 in Q1 2026, which is a result of higher volumes, disciplined cost management and efficient lab operations. As a reminder, we continue to expect Shield cost per test to decline to approximately $200 at scale, driven by further volume growth as well as workflow efficiencies and automation, which we expect to implement in 2027.

Turning to Slide 22. Based on our strong first quarter performance and increased visibility, we are raising our full year 2026 revenue guidance to a range of $1.30 billion to $1.32 billion, representing growth of 32% to 34%. Oncology revenue is now expected to grow 28% to 29% with volume growth of greater than 35%. Demand fundamentals remain strong across the portfolio. Guardant360 Liquid should continue to benefit from Smart App adoption, while Guardant360 Tissue is building on recent upgrades and strong commercial execution.

Reveal is expected to remain our fastest-growing oncology product, driven by MRD and therapy monitoring. Our oncology guidance does not include potential upside from FDA approval of Guardant360 Liquid or the launch of Reveal Ultra. We continue to expect Biopharma & Data to grow in the low double-digit range, supported by recent strategic partnerships, continued progress in our CDx pipeline and a combination of ongoing collaborations and new program starts.

Given the momentum exiting Q1, the impact we're seeing from our DTC and HCP campaigns and the launch of our Quest collaboration, we now expect Screening revenue of $186 million to $198 million, driven by Shield volume of approximately 230,000 to 245,000 tests. Note that this improved outlook does not include upside from ACS guideline inclusion, which we continue to expect in the near term.

We continue to expect full year non-GAAP gross margin in the range of 64% to 65%, which reflects ongoing improvements to Guardant360 Liquid and Shield cost per test, balanced with changes to product mix as Shield and Reveal test volumes scale rapidly. Given the strength and momentum we're seeing with Shield, we plan to continue reinvesting incremental screening gross profit to support commercial expansion during the year.

Accordingly, we now expect 2026 non-GAAP operating expenses to be in the range of $1.05 billion to $1.07 billion, representing growth of 16% to 18% compared to 2025. We continue to expect full year free cash flow burn to be in the range of $185 million to $195 million, representing an improvement year-over-year. Excluding Screening, we expect the remainder of the business to be free cash flow positive for the full year 2026, and we remain committed to achieving company-wide cash flow breakeven by the end of 2027.

Turning to Slide 23, we are executing well against our key 2026 priorities. In Oncology, we will complete the Guardant360 Liquid NovaSeq X transition this month and expect multiple product launches, including Reveal Ultra, FDA-approved Guardant360 Liquid and continued expansion of the Smart platform. Guardant360 Liquid ESR1 monitoring launch is dependent on FDA approval of camizestrant. Last week, the Oncologic Drugs Advisory Committee voted [ 6 to 3 ] against the claim that camizestrant demonstrated clinically meaningful benefit in HR-positive HER2-negative metastatic breast cancer. Ultimately, the FDA retains full discretion over its final decision, and we look forward to that outcome in the coming months.

Importantly, the committee's discussion reinforced the broader consensus that ctDNA companion diagnostic therapy monitoring represents the future of precision oncology care. Furthermore, our revenue guidance does not reflect any impact from the potential approval of camizestrant. If it does receive FDA approval, this could represent a meaningful source of upside to Guardant360.

In Biopharma & Data, we're advancing CDx programs and expanding strategic partnerships, including recent additions with leading biopharma companies and continue to scale our InfinityAI platform.

In Screening, we've launched our Quest collaboration and expanded Shield into Multi-Cancer Detection markets in Asia through our partnership with Manulife.

Overall, the business is delivering very strong growth, and we remain focused on disciplined execution as we scale.

With that, we'll now open the call for questions.

[Operator Instructions] First question is from the line of Mark Massaro with BTIG.

Congrats on the strong beat and raise. I'll stick with the Shield question. So it's nice to see both volumes and revenue come in above my expectations. And you talked about volumes accelerated momentum in March. I was curious if you could just speak to your confidence around April. I would assume that, that is tracking well since you raised the guide. And can you just give us a sense for why you raised the volume guide up for Shield? If I remember this correctly, I believe the prior outlook excluded benefit from Quest. So how much of this might be adding Quest into the calculus versus any other drivers that you're seeing?

Thank you, Mark. Yes, we are very proud of what we did in Q1 in terms of Shield volume. January and February went as we expected. But as we entered March, really we saw such a huge momentum that was way better than actually what we expected. The root cause of it, like multiple things worked all at the same time hand to hand. We talked about launching our DTC campaign, influencer campaigns, Quest went live at the same time, that EMR connectivity actually helped in a very meaningful way. And we saw that actually continue. So based on the trends that we've seen in March, and it's -- we don't want to get into Q2 commentary, but based on everything that we've seen, gives us a lot of good confidence of what we can deliver in this year. And still, we don't want to get ahead of our skis and be too excited with maybe what we've seen. But we are very confident of this new guide that we put out there.

In terms of Quest contribution, we need to capture more data on how much really Quest is helping us incrementally. What we are seeing in terms of early indications are positive. So we are counting on some of that in our new guide, but again, in a very thoughtful way, and we are going to monitor how it goes in the months to come, and we've set the expectation accordingly.

Next question is from the line of Subbu Nambi with Guggenheim.

Congratulations on the print. Helmy, G360, despite being on the market for over a decade, is growing 30% year-over-year. While you have previously said there is no one reason for this outsized growth, could you give us additional color on what is driving this? Is it CRC now starting to adopt Liquid? Is it G360 Testing or something else? And then as we look to full year guidance, how much of the guide raise is attributed to G360 outlook?

Sure. Thanks for the question. Yes, we're very pleased with how, as you said, in its 10th year, Guardant360 continues to grow very nicely. I think a lot of it -- I think when we launched the smart liquid biopsy platform a few years ago, I think a lot of people sort of brushed it off as just a sort of marginal addition to the liquid biopsy space. But this is a fundamental step change in terms of the power of liquid biopsy and its capabilities, allowing us to see phenotype, allowing us to have all these different capabilities that were never possible with liquid biopsy before. And I think you're seeing us lean into that, and you're seeing the adoption begin to grow and grow.

So I think it's -- when we dig in and we peel down another layer, there's certainly, I would say, in this inning, a lot of share gains that are happening. There is greater depth and greater breadth as well in terms of physicians that haven't traditionally used liquid biopsy for certain tumor types. But I think all in all, the growth is very broad-based. And I think what's even more exciting is that we're still very much in the early innings of the platform's capabilities in terms of what we can do on the Smart App side as well as the longitudinal testing. I mean we're still not testing at every progression, still very underpenetrated. And so that's the exciting part is that we're very confident that the growth continue not only in the short term, but the medium to long term as well.

The next question is from the line of Patrick Donnelly with Citi.

Helmy, maybe one for you on the Reveal side. I think you talked about over 100% growth there. Can you just talk about what you're seeing in the market, the key drivers there? And then I know you mentioned you submitted a few data packages to MolDx on breast cancer surveillance, some of the monitoring pieces. Maybe just talk about the catalyst set on that front on the reimbursement side, what we should be looking for on the Reveal front?

Yes. We're very excited with how fast Reveal is growing, how much depth we're seeing there. Part of the drivers are -- we're still continuing to see really good growth in CRC, breast and lung cancers and the surveillance setting. But therapy monitoring has also been a great addition to the portfolio, and we're seeing, I think, great traction there. I think what that shows is really the brands that we've built over the last 12 years in oncology. And when we launch something new, we tend to see, I think, outsized traction maybe versus, let's say, a new competitor in the market.

And then we're making progress with our MolDX submissions. I think the nice thing is the volume is sort of leading indicator. You can't generate revenue without the volume. And hopefully when we get over the finish line with some of the submissions, they will really be in a good spot from a revenue and sort of overall ASP for the MRD business that we have.

Next question is from the line of Doug Schenkel with Wolfe Research.

This is Colleen on for Doug. We've got a question on Shield ASPs expectations. So it looks like ASP is holding up a little bit better than we had expected. And if we're doing the math right, it looks like you're expecting full year '26 Shield ASPs a bit north of $800 per test. If possible, could you share what percentage of Shield volume came from CMS in the quarter and how you expect that to evolve over the year?

Yes, I can take that. Q1 was pretty consistent with what we saw towards the back end of last year with a pretty high proportion of Shield tests being either Medicare -- fee-for-service or Medicare Advantage. And so that's what's been driving that strong ASP over the last few quarters.

As we look out for the remainder of the year, we're expecting to sort of broaden the reach to patients under 65. And of course, we're not covered yet on the commercial side. And so I think our sort of expectation and our guide sort of implies a tick down in the ASP for the remainder of the year as we build out that commercial patient volume and getting ahead of when we start to get the reimbursement. So yes, today, it's been strong. It's predominantly Medicare, Medicare Advantage, but that sort of mix is going to skew a little bit more to [ under 65s ] throughout the year.

Next question is from the line of Casey Woodring with JPMorgan.

This is Sebastian Sandler on for Casey. Can you dig a little more into the G360 Tissue growth you're seeing? You're growing well above the market. So it seems like you're taking some share there. I'm just curious how sustainable maybe some of these share gains are? And then can you talk about the pathway to ASP upside from this whole transcriptome addition? I would expect that would be more than the $300 benefit you saw from the initial RNA element.

Yes. Great question. Yes, obviously, we're very pleased with the growth we're seeing in Tissue. And we think one of the things that will sort of further accelerate that growth is as we get FDA approval for our Guardant360 Liquid test. And we think that will really streamline the portfolio, allow simplified ordering between the 2 products and really help move everything on to the Smart platform. And so yes, we believe this growth is sustainable. But right now, sort of the trajectory is being led by Guardant360 Liquid in terms of just how advanced those capabilities are. But the nice thing is that G360 Tissue will also have a lot of the same Smart Apps over time. And so we think essentially Tissue can just draft behind really, I think, amazing growth we're seeing with our Liquid portfolio.

In terms of old transcriptome, maybe if we take a step back, I think the overall sort of trajectory or pathway we're seeing with G360 Tissue is that obviously, that will go through its own regulatory pathway. We'll submit that to the FDA at some point. And we believe we can qualify for essentially ADLT status there as well, which should improve ASP further substantially.

The next question is from the line of Puneet Souda with Leerink Partners.

First one on Shield, 90% adherence rate, that is impressive, something, AmirAli, you've been pointing out for some time, just as you were pointing out FDA approval of Shield and both of those obviously coming to fruition here. So I really like the consistency and insight here. But could you talk about the Shield volume cadence through the year? How should we think about the next 3 quarters just given the momentum you're seeing and the effort around the key ads and the marketing and all of that you're putting, DTC that you're putting behind Shield? And on the oncology side, Helmy, G360 repeat use is an important driver. Cami AdCom was resoundingly positive for G360 and ctDNA use. But the problem was the trial design not the assay. Going forward, how should we think about the repeat use from 1.3 average? How does that go higher in the future?

Thank you, Puneet. So our guide for this year now for Shield, when you do the calculation, it kind of implies an average of about maybe a little bit over 10,000 sequential growth like Q-over-Q. And as I mentioned earlier, we feel very confident about this new guidance. And we'll see how it goes. Again, we didn't want to get ahead of our skis. We want to capture more data of how our DTC campaigns are going to continue to impact our volume, how Quest is going to contribute, how much more we can see the rep productivity is going to go up. We continue to hire reps. We have that element, too. But currently, this new guide, I think, is the right guide that we feel very confident of a little bit over 10,000 Q-over-Q growth.

In terms of the 1.3 average that you mentioned on G360, I think -- what we see is that there are multiple shots on goal to getting, I think, this feature that everyone believes in, which is going from biopsies and scans to just using the power of smart liquid biopsy and blood to monitor patients adaptively and dynamically. And so there are multiple shots on goal there. And I think the primary one is going to be using really the 1, 2 punch of Guardant360 Liquid and Reveal for monitoring. And then as Reveal ebbs and flows, it will be a much simpler way to reflex patients to essentially a G360 test in those patients if and when those patients progress. And so we think this feature will happen. It's starting to happen now with the launch of Reveal for therapy monitoring, which we're seeing exciting traction for. And we're very confident that regardless of how camizestrant turns out, the future of oncology and the future of therapy switching will involve ctDNA.

The next question is from the line of Dan Arias with Stifel.

Helmy, on that point, on the camizestrant AdCom, some of the folks on the committee seem to suggest that the vote for them would have been a yes if there was an overall survival benefit. From where you sit, are the trials that might be on deck here set up endpoint-wise to show that? What do we have coming to us in terms of evidence generation and getting over the hump there on what these folks might need to see?

Yes. I mean, obviously, we don't want to comment on the specifics of any one trial. But yes, we're very confident that over time there are other trials that I think are going to sort of push the envelope. It's always hard for the first paradigm shift. And there's always a mountain of evidence that's required from -- moving from one paradigm from one modality to another one. But once that dam is broken, it's very hard to go back to the previous paradigm. And so it's just a matter of when, not if, and we're very confident we'll get there over the next few years, if not sooner.

The next question is from the line of Kyle Mikson with Canaccord.

Congrats on the quarter. Mike, on the ASP for Shield, and this was touched on earlier, but it looks like the rest of the year ASP implied in the guide, the new guide is like high 500s. I'm just curious what you're assuming in terms of mix and why would it be that low? That's quite obviously. And then secondly, on -- maybe just a broader question, perhaps Helmy can answer this. So we have this acquisition today of an AI-based kind of diagnostics company. Is this -- I mean I know it's like one example, but are you guys thinking about ways to kind of step up your AI game and offer AI-based companion diagnostics or anything of that sort?

Yes, Kyle, I'll take the Shield ASP question first. Now actually, if you look at our guide on the volume increase and the revenue increase, what it implies is for Q2 through Q4, on average, the ASP is around $775, which is effectively the same sort of guide that we gave for that part of the year back in February. So there's no change. And yes, as I mentioned before, what's driving that tick down from Q1, which is very strong, is going to be just the mix of Medicare, Medicare Advantage versus commercial patients where we're not getting paid now.

Yes. In terms of the AI question, I feel like we've been leading the pack, frankly, in terms of real AI that has that actionable insight. There's a lot of talk about AI in the space, but I think you can see physicians voting with their feet when they're using our products much more than others in the space right now. And we were one of the -- we are the first to bring AI pathology to the oncology space with the Lunit collaboration we did a few years ago. You're seeing what we're doing with InfinityAI. I think we'll be one of the first to amass an exabyte of data. And data is really the raw fuel that's required to use AI to have truly actionable insights. And so we built an architecture that's purpose-built from the ground up to be really deployed and utilized and worked with AI in, I think, very fruitful way. And yes, you're going to see, I would say, over the coming quarters us really sharing a lot more in terms of all the exciting things that we're building with AI and with the enormous treasury of data that we have inside the company.

Next question is from the line of Tycho Peterson with Jefferies.

A couple of quick ones. I guess you've had a couple on SERENA-6. Just a different angle, though. How does this change your time lines for establishing therapy monitoring as a standard billable event versus just therapy selection? Does this kind of extend the adoption curve and other lessons learned from this trial as we think about other high-volume areas like lung and CRC surveillance. So that's one question.

Second is consolidation that came up in an earlier question. There's been a lot. How are you thinking about competitive landscape? I mean now you've got Roche with Saga. Obviously, Abbott with Exact. Just curious if that changes your thoughts on size of sales channel, go-to-market strategy at all?

And then for Mike, was there any weather impact? I've had a few people asking if there's going to be any catch-up in 2Q. Obviously, you grew through it, but was there any headwind from PCP visit cancellations?

In terms of the SERENA-6 question, our primary shots on goal there are frankly, the Reveal therapy monitoring we just launched and the reimbursement packages we have on deck in terms of IO therapy monitoring, chemotherapy monitoring, which are really the primary modalities and tools and the therapies in oncology therapy space right now. And so with those 2 over the finish line, I think we'll be in a very, very good spot from a therapy monitoring point of view. And as we said, things like SERENA-6 and specific trials are frankly, upside really to that primary pathway.

In terms of consolidation, we look at almost, I think every company in the space always thinking about balancing organic growth with inorganic growth. But as you can see, the bar is very high in terms of what we built organically inside the company, the growth rates, the quality of our products and so on. And so it really has to be something that is accretive to what we built here. But yes, I think it will happen at some point.

Yes. And then with respect to the weather impact, I mean, in Q1, we saw the normal seasonal impact related to sort of PCP footfall as well as weather. That was expected. That was in our original guide. And so the start of the year came in, yes, again, as we expected. So no, we don't anticipate any catch-up. I think what we saw in the start of the year was just what we would normally expect to see every year.

Next question is from the line of Bill Bonello with Craig-Hallum.

I have maybe a slightly bigger picture question, but that's just sort of getting at the importance of the portfolio that you've built out. Just curious if you can give us some sense of the percentage of customers that are ordering multiple products, so say, G360 Liquid and Tissue and Reveal. And then maybe along with that, with this growth, how much of it is sort of competitive takeaway versus docs that might be using some of these products, let's say, de novo?

Yes, it's a great question. Those are numbers that keep going up every single quarter in terms of the depth of ordering, not just the number of patients that the physician may have where they're ordering, let's say, a single product from us, but really the number of essentially linked products we have where there may be a CDx cluster tissue and then the physician may be sort of monitoring those patients or they may be using an MRD product from us for another patient subset. And that is really the power of the platform really this idea that all these products are all linked. And I think that is why having such a comprehensive portfolio is so important because essentially any one of those products with their best-in-class can help convert those users and those physicians to Guardant evangelist.

And I would say that for the -- like de novo versus the sort of users, we have something like, I think, 10,000, 11,000 oncologists who order from us certainly on a quarterly kind of basis. And so it's very hard to sort of gain shares in terms of de novo physicians at this point. So it's mostly that. I would say it's a balance of greater depth in terms of percentage of patients that are sort of Guardant360 or Guardant products are being utilized and then certainly, share gains as well. And then I think the exciting part is, obviously, there's a longitudinal aspect that we're barely penetrated and which I think will lead to, I think, growth for the coming years across the portfolio.

Next question is from the line of Michael Ryskin with Bank of America.

Congrats on the quarter again. Maybe sort of a big picture one. There's been a little bit of a land grab among some of your competitors on the market access in terms of expanding sales force building out as they launch new products and as they try to scale their existing products. Just curious what your internal plans are for commercial sales force, where you're expanding, where you're investing and just sort of across the portfolio, if you could walk us through the rest of the year, where you see some of that incremental OpEx going?

On the oncology side, this has been a matter, of course, now for a number of years where we look at revenue per territory per rep. And as long as there's no saturation in that territory, we may split it, we may add additional reps, additional support staff. And so that's just a matter of good hygiene for us, and we'll continue to do that where we see positive ROI. But I would say that I think we've prided ourselves on fairly high, maybe industry best sales efficiency. And so we will always try to do it in the most efficient way. But yes, we're not going to sort of skim on sales and marketing where there's positive ROI.

On the Screening side, as we talked about it before, any additional gross profit in terms of year-over-year is getting reinvested in building the S&M function. They have a very good traction that goes into hiring additional sales force now is going towards these marketing campaigns like DTC campaign that we talked about earlier. It's kind of very interesting, in fact, I heard from our Head of Sales, and we are continuing to hire this year, too, that even the quality of the reps that we are hiring continues to go up. So we are very excited with what we are seeing right now.

The next question is from the line of Dan Brennan with TD Cowen.

Maybe one on G360 and just one on multi-cancer. So on G360, really nice quarter, 30% volume growth, well above expectations. I know there was a comment question or 2 earlier, but just can you speak to a little bit again like what was better than you thought to drive that kind of volume growth? And then b, kind of implicit within the new 35% oncology volume growth, how are you thinking about G360? And then just on multi-cancer, can you just remind us of the strategy there? When we'll learn more? You're obviously having the ability to have patients opt in. What's the timetable at which we will get some clarity on the regulatory plan there? I know you've been bullish about the number of samples you'll be collecting, but just wondering how we think about the path forward there.

In terms of G360, I don't think there was anything that kind of completely surprised us. I mean I think we know that the test is really best-in-class offers a lot of capabilities that, frankly, are not available in the market. And I think we're just continuing to lean into that. When we think about the rest of the year, I think beginning, we said something like 20% year-over-year growth for G360. That's obviously with a strong quarter inching up. And we're going to continue pushing the Vision G360 out there. The FDA approval of G360 should be another major catalyst that hopefully will be even upside to this current forecast.

On the MCD front, this option rate is going strong. And with the strategy that we have, we are on track to have the biggest clinical database of MCD testing and the value on the patient from U.S. patient population in near future. So still we have a couple of milestones to hit to build that database. So let us get there and then we would set the right expectation for the timing of the regulatory milestones. But we are pleased with what we are seeing today.

The next question is from the line of Brandon Couillard with Wells Fargo.

A couple on Shield. How many reps do you expect to have on board exiting the year at this point in the context of the higher revenue guide? Number two, do you expect only needing 2 blood tubes to be a volume driver? And number three, on ACS guidelines, why don't you think they've been published yet? Are you able to share any feedback from maybe some of your interactions with the organization?

Yes. So we entered this year with like the 300 reps that we talked about. And as I mentioned, this incremental gross profit that we're going to have this year is going to get reinvested back. We are not planning to just give like pipe-by-pipe kind of updates on the size of the sales team as the field is becoming competitive, and that's commercially sensitive information. But based on this high-level guide, I think you guys are well positioned to have some estimation of how many people we are going to have by end of, let's say, 2026.

In terms of 2-tubes, on one side, we didn't hear any kind of issue with 4-tube, but we always want to have the best-in-class, easiest customer experience with Guardant products. As a result, we worked on studies to reduce the 4-tubes even to 2-tube, and we are very pleased that we got the approval from FDA, and we are going live with that updated kit in very near future.

In terms of ACS guideline, I know you guys are hearing from me. It's coming. It's coming now probably for over a year. And my answer is the same. I think it's going to come any day, but I've been kind of a broken record on it. Our conversation with them continues to be actually pretty positive, and looks like everything is done. So we are just waiting for the finalized guidelines to be published. So it should be any day, but we'll see.

Last question, please.

Final question is from the line of Bradley Bowers with Mizuho.

Just wanted to maybe double-click on where you're kind of seeing the Reveal volume growth. The pricing doesn't lend itself to be in Medicare CRC, but maybe I'm wrong. But just based on KOL checks, that area may be preferring Tissue. Just wanted to see where you're kind of seeing some of the volume growth ahead of expectation and maybe what the expectations for volume and price lift should be post-breast?

Yes. I would say we're seeing growth, frankly, across the board. CRC, breast has been very strong for us, lung. And then obviously, new indication of therapy monitoring has been relatively strong for us as well. So yes, I think the market really has, I would say, sort of 2 parts to it. The consumer-informed sort of MRD subset and then certainly market as well that is very, very sizable. Right now we're the far and away leader in tissue-free MRD, and we're continuing to lean into that. And obviously we'll be excited when we dip our toes into more informed with Reveal coming later this year. I'll let maybe Mike talk about ASP.

Yes. No, ASP continues to be in this range, $600 to $700. I think we're excited hopefully to get incremental MolDx coverage in the near future with the breast and IO and chemo submissions that we've made. So obviously, getting Medicare coverage for each of those is going to have a nice positive impact. So definitely, breast is a large portion of the volume now. And so if we get that, it will definitely take us beyond the current range that we're in and sort of move us step-by-step closer to the $1,000 target that we set for 2028. So I think getting that coverage is going to be very positive for us.

No additional questions waiting at this time. So I'll pass the call back to management for any closing remarks.

That's it. Thank you, Matt.

That concludes the conference call. Thank you for your participation. You may now disconnect your lines.

Good afternoon, everybody. I'm Luke Sergott, I cover life science tools and diagnostics here at Barclays. With me, I have AmirAli Talasaz, co-CEO; and Mike Bell, CFO of Guardant Health. I thought I wasn't going to try your last name, but I did it anyway. Thanks again for making it.

Thanks for having us.

Yes, great. I think that I just wanted to come off the jump. I mean there's a couple of conversations that we've been having around SERENA-6, right? Couple of fierce biotech or fierce articles out there around really the kind of the protocol design, et cetera. But in the articles and in the conversations, they've talked about like the clinical utility of discovering the ESR1 mutation. And it's broader kind of clinical utility question on the liquid biopsy side anyway, but I think that -- can you just kind of walk through where you see the clear clinical utility and the benefit to the patients and getting the test and making that switch without having to talk about the drug itself or anything like that.

Yes, sure. So maybe for some of the people who could be near to story at Guardant. We have 3 major actual business drivers and brands around treatment selection, MRD and screening, all of them are giving us opportunities for hyper growth. And the question about SERENA-6. One of the growth drivers for Guardant360, our liquid CGP test for treatment of selection is making the liquid testing also a monitoring tool while the patients are going through the treatment selection phase. .

We got ESR1 approval from FDA a couple of years ago in breast cancer for treatment selection. And what happened right after the FDA approval, the volume of our breast cancer testing as of very few weeks doubled up. It's an emerging mutation that happens as mechanism of resistance response, and it's activating some other kind of opportunities for treatment for patients. Now within the SERENA-6 trial, our pharma partner AstraZeneca at this time, is monitoring the patient to figure out when ESR1 is getting detected in blood and using that as a surrogate for changing the decision on the treatment and starting kind of therapy.

And that trial readout actually has been very interesting. It's got discussed in ASCO and the expected decision by FDA for FDA approval is in the near future in the first half of this year. Now it's a biomarker that uniquely can just be detected for liquid biopsy. It takes our liquid biopsy at a single time point testing at each round of progression to multiple time points of testing initially for breast cancer for this ESR1, but it could open up a utility over time to similar kind of studies and similar kind of biomarker testing in monitored setting.

The utility of this drug actually is pretty interesting, like when you are looking at the response rate that's pretty strong our pharma partner, AstraZeneca, it looks like they are very bullish about the opportunity with this drug. They're getting ready to launch this test. And there's an AdCom to talk about the drug actually in late May.

What we do know is whenever FDA want to approve something which could be paradigm change in clinical decision-making. It could be a big event. They want to actually call for AdComs and get some opinions from KOLs, that's actually we experienced that with some other brands at Guardant ourselves. And for SERENA-6, since the patients are not first line or second line, they are falling kind of between these two, it is an interesting new paradigm for oncology management. So it makes sense for FDA to go through this process. We are very positive and hopeful that would go smoothly.

And I guess just on the whole -- the SERD space, we have a Roche readout also come through. I assume that you guys are involved across the board on the indication. And as you think about that, like what that means for the particular biomarker within the franchise. And I know you guys don't have it in your '26 guide, but as we think about '27 and '28, how instrumental is this approval or if the drug comes on, like what can that do to the overall outlook?

It's a very good growth driver actually for Guardant360. There are 40,000 breast cancer patients who are candidates for this kind of monitoring if this drug gets approved for this indication. And 3, 4 time point of testing per year for these kind of patients. And if the patients actually still continue to be SR1 negative, testing would continue in the second year. But we expect, on average, maybe 3 to 4 testing per year. It's a very interesting growth driver for us. It's not part of our guide in 2026. We want to wait for FDA approval to secure that and then we see actually what happens to our breast volume, post approval, it could be something very interesting for us. .

Would this be included on the companion side? Or is this just where the HER2, whatever the indication is for the 40,000 breast cancer patients, it's associated with Astra's drug, right?

It's going to be a new CDx for Guardant360. It's kind of a first of its kind, it's going to be the first monitoring CDx for Guardant360. We already have 25 approvals for 360, but all of them are by companion to drug specifically for treatment decision-making at a single time point, but this one would be monitoring CDx.

Okay. yes, like you said, first of its kind. Sticking in G360 the recent liquid approval marries really well with the tissue side. And I think that there's a little bit of an unappreciated understanding of how these 2 are going to be married together and all -- kind of offered is like for a bundling opportunity. Can you talk about that?

Yes, actually, very recently, I think maybe what you're referring to, look, is the CRC approval that 360 got in January, we got the first approval for 360 in CRC indication. It's new for us. And the utility of CGP and CRC is well established, but always there are some physicians that once the test is indicated for specific FDA-approved indication, actually, the level of confidence even goes higher and the level of utilization goes higher. So that could have some kind of interesting impact.

It also drives some kind of new conversation with commercial payers to fill some of the gaps that still we have on the coverage side. after 10 years, we are in a very good position with 360 reimbursement, but there are still some cases that we are not getting good payment from the payers. And our experience has shown that once we get actually FDA approval, our conversation with commercial payers who do specific indication becomes even much more solid. So that could have some kind of a tailwind for us on the coverage and ASP front. But it's going to take some time.

Yes. It'll take time to build that out -- for that to build. On the -- as you think about the platform itself, you guys really made your bet on the methylation with Infinity a long time ago, but as you see the sequencing costs come down and the elasticity pick up was the amount of data you can put out. Talk about your -- the platform strategy and layering on more of multiomics. Or are you guys kind of just continue and adding indications for your existing technology?

So this is really the data mode that we have in Guardant story, the flywheel of data at Guardant. When we are looking at 1 million patient data that we have on the genomics side, that's very deep. When we are looking at the epigenomics side, that's something that internally, we even call it is a dark matter of biology and our understanding of cancer. We have many hundreds of thousands of patients that we have actually full epigenomic data in them. .

That's a treasure that's already paying some dividend for us in terms of technology development, application development for us, like what we are doing on 360 franchise based on this epigenomic data, just to give you some example, we developed some smart apps that is generating some kind of clinical information for physicians for first time, like subtyping the patient has been enabled by this database and is one of our smart apps just as an example.

We are adding some other kind of layers to our data step by step. We talked about our recent MetaSight acquisition, which is generating a new layer of complementary technology for us and that would potentially because even beyond CTD and analysis, genomic, epigenomic analysis and it was a new layer information, which has potential for improvements of our product across the whole portfolio.

Great. And then let's shift gears, I guess, when you talk about Reveal, this is the fastest growing test in your portfolio. we have somewhere around 60,000 tests. It would be great to know them in the right ballpark there. But outside of that, as you continue to land, obviously, it's really early in the launch of most of these, I assume, are on the adjuvant side, but -- how are you guys thinking about the surveillance portion, it was promise -- not promise, but the idea was that surveillance will include like 3 or 4 tests a year, and that's quickly been kind of walked back to 1 or 2. So walk me through kind of that waterfall and how you think it builds. .

Mike, do you want to take that?

Yes. I mean, first of all, we don't break out our Reveal volumes, but I think the number you said, 60,000. I mean it's broadly in the right ballpark. And yes, it's been our fastest-growing oncology product by volume for the last few years. And we expect -- it's going to continue to be so this year. We're very bullish on Reveal for 2026.

On the adjuvant surveillance side, we're not sort of breaking that out. But what I would say is that on the CRC side, where we're now reimbursed for CRC surveillance since roughly 12 months ago, Yes. I mean, we're seeing good traction there. We're seeing good pull through. I think there's been a focus from our commercial operations to refocus on the surveillance aspect and making sure that we've got the mechanisms in the pull through the patient for the second, third, further test. So it's definitely an opportunity for us. It's more that way, I'd say we're improving. And that sort of test per patient is getting better. And so yes, again, Reveal on both the adjuvant and the surveillance for us is very important.

And as you think about the submitted breast to submitted I/O, [indiscernible] MolDX, how does the actual treatment paradigm change versus CRC with breast or immuno-oncology. The reason I ask is because like with CRC, if you come back, you're starting to see the signal again, you can go back in and identify and cut that out. But with breast, you've already probably done the double mastectomy or it's more about a treatment and a clinical utility question there associated with those. So how does that paradigm change as you kind of -- as you're rolling out in these new indications? Is that way off? .

So I think typically post more details in the next for a patient is to do radiographic imaging to find where that site of residual disease is or then make some kind of treatment decisions just based on that MRD finding. But what you're pointing out actually generates some kind of interesting opportunity, which -- could we actually paradigm shifter in the field of MRD. Just imagine a day that the patients who's going through MRD testing, not only you can figure out if the patient is MRD positive or negative, but also where the site of residual disease is through the same test. These are some of the applications or opportunities that platform technologies that we have has potential to deliver versus just yes, no quantification level of residual disease in body. So we are very excited to potentially see those kind of future opportunities in the field of MRD. .

Yes. So outside of the counting application, almost like tissue version like you've seen with some of the [ MSI ] side.

If they have got potential for it. .

Yes. Is that a big technology lift? Or is that just.

Look, like the science of it like already when, for instance, we have blood tests for multi-cancer detection that we do that has cancer side of origin as part of it. There are some aspects of science and technology and understanding that we have. We are also capturing some additional layers of the data. What I'm talking about is not in terms of prime time, but really like figuring out and seeing a vision for future where we could be that in this field of MRD, not only we find it, but we can also locate it and characterize it and provide additional information about that residual disease.

Got you. And then, I guess, sticking with Reveal here with the Reveal Ultra launch. You don't have this in the guide. Walk us through like I guess, why not included in the guide? And I understand that there's a healthy dose of conservatism and uncertainty with how this kind of paces out. But you already have kind of the sales force in place ready to build this out. And so early feedback from physicians and then timing of when we could start seeing this. .

So we are -- maybe just some background maybe for some of the people who are newer to the story. We are already a leader in the tumor-naive MRD side. And now we mentioned we are kind of get into a tumor-informed MRD testing with Reveal Ultra. It's a new technology stack that we are we built ground up. We believe it's going to be the best-in-class technology when we launch it. It's on track to get launched later this year. .

Now in terms of the guide, it's a product that still we have not launched. And when we launch it, it's not going to -- we are kind of the data, but probably no reimbursement right off the bat. So we are not counting it as a revenue contributor in 2026, but it's definitely an interesting development for us as we go to 2027.

Right. And then from a reimbursement perspective, you kind of give us a specific number you're targeting? Or is it going to be similar to what Reveal is? Is it going to change at all? .

I think that's to be determined. CRC, we're reimbursed at $1,644. Our sort of base case assumption is that the reimbursement would be in that ballpark. But I think -- we'll have to see as we go through the MolDx process, there'll have to be sort of discussions on that, and we'll see where we come out. But yes, I mean we're hopeful for reimbursement as soon as possible, and we're hoping for the right reimbursement level. .

All right. And then lastly here on Ultra. I mean what really stood out was the limited detection to us, like how did you get it so low? I mean, how deep are you sequencing? Is it just a matter of just brute force or is there something more elegant? .

I think by now, we should have developed this confidence at Guardant, we really have very strong muscle power and innovation and going after hard problems, which if we can solve it would be a major contribution to the field. So we've shown it across multiple products and now Reveal Ultra would be the newest example. So we haven't disclosed details about the technology stack, but we are not far away from the launch when we get there. We are going to have some interesting conversations taking enough. .

All right. And then I guess moving through the portfolio as we talk about screening, and this is -- it was -- we talked about Guardant back even back in the day, 2016 and '17, like this is it, like this is this big opportunity, and now it's here. And you have G360 still go on strong and you have Reveal on MRD, right? So a lot broader portfolio, but as you think about the screening and the ramp here that you've seen, a little bit more mature market, how much of the adoption you've seen? How much of that is closing the care gap from those that haven't had some prior screening technology and I just don't want to get colonoscopy or use a stool-based test?

Maybe I just make a general comment about the whole portfolio, and then maybe I go through Shield specifically, a mature gap question. So to your point, look like we've done several things at Guardant during the last few years that all of them became kind of got ready almost at the same time to really contribute in a very meaningful growth driver. We are very excited, confident and bullish about continuity of Guardant360 growth, powered by small platform, some of the new incisions and going through early stage, a bunch of growth drivers that we are seeing on 360 that gives us a lot of content there.

MRD, we talked about it earlier, had Shield. This is probably the biggest diagnostic brand ever. In the first full year of launch, we made it outside COVID testing, the best diagnostic launch, it's really an endorsement of the unmet need, which is out there. And we have a blood test that this time, we are really messaging for on-screen patient population to get tested in PCPs, that's the biggest piece of untapped opportunity, 54 million patient opportunity there.

And what we've seen in some of the latest data that I've seen is about 90% of the patients who have been tested by Shield, they haven't been screened during last 5 years based on their medical information that we have, which means really our messaging is working, and we are feeling the gap of really bringing on screen patient population around the table. At the end, this is a simple routine blades that 90% of the patients age 50 and above do it on annual basis and Shield is just getting added and we are very excited of what's happening there.

And you're exiting the year with 300 reps. You guys are guiding 150% volume growth. Do you have ACS and [indiscernible] and USPSTF baked in? Just walk through the assumptions there on this growth? And is it more about just increased productivity on your existing reps? .

Effectively, that's right. We've not included been in ACS guidelines in our guidance, neither been in quality metrics or USPSTF. And we look at ACS guidelines as being in the relatively near future, and so that would be an upside. Yes, the main driver is just going to continue to be execution on the commercial side. We ended the year with -- we ended last year with 300 sales reps. We're going to add to that this year. But those 300 -- the productivity is going to be increasing throughout the year. We'll bring on new reps, we'll put them into new territories.

So I think the field sales is going to be a main driver of that. We've started now a DTC campaign. We're very hopeful for that with the early days very promising. So we think that's going to be a driver of growth we announced just today a partnership with Quest. That gets us really to fasttrack our EMR connectivity. So we're assuming that that's also going to be a driver, and that's in our guidance. What we haven't included from the Quest partnership is the reps are going to be calling on their accounts to educate them about Shield. We're going to be able to utilize that to send in our reps as well and drive volume into those accounts. We haven't baked that into our guidance. If that's successful and it works well, I think that could be a potential upside of what we've guided to. So we think we've got a lot of drivers already in that guidance, but we've left ourselves some room for potential upside.

Yes, I mean, it makes sense. You guys have -- you haven't worked with them before, so you don't really know how that's going to play out. But from a coverage perspective on those 300 reps and maybe adding a few more, but how do you guys have that structured? How is that -- because there's a lot of PCPs out there and a lot of them are, let's say, not as conducive to growth as some might others be? So like how are you guys kind of segmenting the market and going after it versus [indiscernible] of the ocean, I would say.

We launched in a very targeted way. We have targeted the people who have experience with noninvasive CRC screening. In early days, we really targeted people who are super users of noninvasive CRC screening, good volume of Medicare beneficiaries since that's the reimbursement that we had at the time of launch. Now with this 300 and continuing to increase reps, we have a nationwide coverage, but still, there are 250,000 potential PCPs we have experienced with CRC screening, and we are just scratching the surface. We are just opening up this opportunity, and there is a lot of room of potential growth is left, obviously. So -- but in terms of coverage now, we have nationwide coverage. .

Yes. And I guess as from your thinking about building up the next year or 2 of the business, it's more focusing on those patients that are noncompliant, right? Or are you starting to go into the hand-to-hand combat with some of the stool-based testing? .

No, not yet, I think obviously, our coverage is broad. Our indication in terms of FDA approval, this first line is broad, but we are after screening on screen patient population. That's the vegus untapped opportunity. But we are already seeing -- although we are not promising it, we are seeing actually cases in some accounts that they have some other interesting use cases. For instance, we are seeing when the patient is due for rescreening, some of the patients are really opting out of continuing with the previous modality and blood is a great opportunity for that. Some patients are getting tested between 2 interval colonoscopy. There are some incidental CRCs that we know are getting diagnosed as interval CRC. So there are some interesting cases that we are seeing in terms of market adoption, but we are focused on the screen patient population.

All right. And I know we're over time. But just on the DTC side, so if I went on like and tried to go get screened, could I just log in and just get one sentence in there? Or -- like how is this -- is this more about just educating the consumers so that they can go to their PCP and get it...

You're targeting 45 and above and double indexing on 65 and above.

[indiscernible].

But yes, I think you're seeing some heavy kind of presence in the digital side, some presence on TV, but still, we are not doing full force DTC campaigns. But step by step, we are pleased with what we are seeing. .

Great. All right, everybody. Thank you.

Thank you.

Good afternoon. Thank you for attending the Guardant Health Q4 2025 Earnings Call. My name is Cameron, and I'll be your moderator for today. [Operator Instructions]

I would now like to pass the conference over to your host, Zarak Khurshid, VP of Investor Relations. You may proceed.

Thank you. Earlier today, Guardant Health released financial results for the quarter and year ended December 31, 2025. Joining me today from Guardant are Helmy Eltoukhy, Co-CEO; AmirAli Talasaz, Co-CEO; and Mike Bell, Chief Financial Officer.

Before we begin, I'd like to remind you that during this call, management will make forward-looking statements within the meaning of Federal Securities laws. These statements involve material risks and uncertainties that could cause actual results or events to materially differ from those anticipated. This call will also include a discussion of non-GAAP financial measures, which are adjusted to exclude certain specified items. Additional information regarding material risks and uncertainties as well as the non-GAAP financial reconciliations to most directly to variable GAAP financial measures are available in the press release Guardant issued today as well as in our 10-K and other filings with the SEC. Guardant disclaims any intention or obligation to update or revise financial projections and forward-looking statements, whether because of new information, future events or otherwise, except as required by law. The information in this conference call is accurate only as of the live broadcast.

With that, I would like to turn the call over to Helmy.

Thanks, Zarak. Good afternoon, and thank you for joining our fourth quarter and full year 2025 earnings call. Starting on Slide 3. 2025 was a breakout year Guardant, where years of investment continues to fuel breakthrough innovation and best-in-class execution across our portfolio. In Oncology, we introduced groundbreaking applications with Guardant360 Liquid, upgraded Guardant360 Tissue onto our smart platform and expanded reveal to support therapy monitoring. In screening, we expanded shield to include a multi-cancer detection results report. At the same time, we made significant progress driving adoption across the portfolio. We have seen exceptional growth in our Oncology business, primarily due to the new capabilities and insights enabled by our smart apps that are increasing both the breadth and depth of ordering of Guardant360 more than a decade after its launch. In MRD, we received Medicare coverage for CRC surveillance in early 2025, and growing clinical data generation for the vial positions us well for additional reimbursement coverage this year. And 2025 represents the first full year for Shield IVD, where very meaningful volume and revenue generation exceeds our expectations.

We have significantly expanded the commercial team and established impactful strategic partnerships to meet the growing demand for a high-performing, blood-based screening options. These advancements reflect outgrowing execution at scale as we deliver actionable insights to physicians and patients across the care continuum. Importantly, this execution has directly driven strong financial performance, both accelerating our top line growth and strengthening our path to profitability.

Now I'd like to share a story that illustrates the real world impact of tests. A 60-year-old man had gone his entire life without being scraped or colorectal cancer despite repeated recommendations from his position each year to undergo a colonoscopy. Although, he agreed to stool-based testing on several occasions, the kits were never completed once they arrive at his home. During a routine office visit, the patient was off of the Shield blood test, which we agreed to and the test was completed that same day in the office. The Shield result was positive, which motivated the patient to undergo his very first colonoscopy following his physicians recommendation. The colonoscopy identified Stage I colon cancer and the patient was quickly scheduled for surgery. Because the cancer was caught early, he has been informed that his treatment is likely curative. The patient expressed deep gratitude for the accessibility and ease of use of the shield blood-based test, which removed a long-standing barrier to screening and ultimately delivered a life-changing result.

Turning to top line performance on Slide 4. We delivered $281 million of revenue in the fourth quarter, representing 39% year-over-year growth and $982 million of revenue or 33% year-over-year growth for the full year. This exceptional performance reflects continued broad-based growth across our oncology screening and biopharma and data businesses.

Taking a closer look at our Oncology business on Slide 5. Oncology revenue increased 30% to $190 million, and oncology volumes grew 38% to approximately 79,000 tests in the fourth quarter.

Turning to Slide 6. Our Smart platform is driving a clear step change in oncology volumes. Guardant360 continues to benefit from a consistent rollout of new smart platform applications, which drive deeper clinical adoption. Guardant360 Tissue gained traction following the major product upgrade release in the second quarter of 2025 and reveal volumes have benefited from Medicare reimbursement for CRC surveillance in the first quarter of 2025. Together, these drivers will continue to catalyze very strong growth in our oncology business.

Moving on to Slide 7. With each patient tested, our data repository continues to deepen and diversify, bringing together rapidly growing Smart epigenic profiles, multimodal longitudinal data sets and an expanding set of earlier stage and asymptomatic patient data through REVEAL and Shield. This growing data asset is becoming a durable moat. Each additional test compounds the breadth, quality and uniqueness of our data set, which in turn strengthens the insights we can deliver. By applying our Infinity AI learning engine to this expanding data treasury, we can accelerate therapeutic discovery and biomarker development for our biopharma partners while uncovering new biological insights that reinforce our clinical franchise. The result is a compounding flywheel that steadily increases the clinical utility of our portfolio and expands their impact before we can deliver to physicians and their patients. We have already applied Infinity AI to develop 15 smart applications on Guardant360 Liquid, and we believe these applications meaningfully expand the clinical utility of Guardant360 Liquid while further extending our leadership in the liquid CGP market.

Looking more closely at some of the recent highlights within our Oncology business on Slide 8. All of our oncology products contributed meaningfully to our fourth quarter 38% year-over-year growth in volumes with Guardant360 delivering remarkable volume growth of nearly 30% year-over-year. Reveal continues to be our fastest-growing product, reflecting growing demand for tissue free MRD. We are particularly encouraged by the early uptake of Reveal for late-stage therapy response monitoring launched in the fourth quarter, which is broadening its clinical use. We are advancing the clinical evidence supporting Reveal and recently submitted our chemo monitoring data package to MolDX for Medicare reimbursement and data from our CDK4 monitoring study for publication. We continue to expand in global access in Q4 with the launch of Guardant360 CDx technology with polyclinical [indiscernible], a leading oncology center in Rome, Italy. With approximately 400,000 new malignant tumor cases diagnosed annually across Italy, we are excited to empower oncologists to make more informed treatment decisions for patients with solid tumor cancers.

Turning to Slide 9 to take a closer look at our Reveal data pipeline. We continue to make strong progress in generating and publishing compelling data across multiple cancer types. Based on the Medicare coverage we gained for CRC surveillance, we have now submitted additional data packages to support coverage in breast cancer surveillance, immuno-oncology monitoring and chemo monitoring. As I just mentioned, we also plan to submit the package for CDK4/6 inhibitor monitoring following the publication. We were encouraged to see data from the largest study of MRD in stage III colon cancer published in the Journal of Clinical Oncology, which shows the detecting CTDNA with a review of better predicted recurrence and overall survival than standard energy.

Looking ahead, we have ongoing studies across more than 5 additional [indiscernible] in both the adjuvant and surveillance settings. Together, the growing body of evidence will continue to strengthen the clinical utility of Reveal and support broader adoption in MRD.

Moving on to Slide 10. Building on our leadership in tissue free MRD, we launched Guardant Reveal with therapy monitoring in the fourth quarter, expanding the franchise into a significant new opportunity in late-stage cancer. Physicians can now use a simple blood test to gain a real-time molecular review of treatment response and detect disease progression earlier. While still early in the launch, we have been very encouraged by the initial traction we are seeing. We believe we are building a meaningful competitive moat in our Oncology business through the combined strength of Guardant360 and Reveal. Guardant is uniquely positioned with scaled offerings spanning both treatment selection and monitoring, enabling a more comprehensive view of the patient journey. This differentiation is driving deeper clinical adoption, supporting more integrated ordering patterns and creating a natural synergistic dynamic across the oncology franchise. When used together Guardant360 and Reveal enables seamless approach to therapy selection monitoring and retreatment across the continuum of care. We are also excited about the potential for therapy monitoring with Guardant360, highlighted by the results from the AstraZeneca sponsored SERENA-6 trial. This study demonstrated a progression-free survival benefit when late-stage breast cancer patients were switched to camizestrant following the detection of ESR1 mutations in blood. Upon companion diagnostic approval of Guardant360, we believe this practice-changing protocol could represent a meaningful driver of test volume. Together, these advances reflect the growing role of blood-based monitoring in cancer care.

Shifting gears to our biopharma and data business on Slide 11. We delivered another year of strong performance with revenue growing 18% year-over-year to $210 million in 2025. We are a leader in companion diagnostics with 25 approvals to date across the U.S., Japan and Europe and a robust pipeline of ongoing CDx programs. In the last six months alone, we have announced 5 new CDx approvals for Guardant360 including the U.S. approval last month for the encorafenib combination therapy in patients with BRAF V600E-mutant metastatic colorectal cancer representing the first FDA approval for Guardant360 and CRC. Our biopharma partner base now includes more than 200 companies. And in January, we announced a multiyear agreement with Merck to develop companion diagnostics and commercialized valvotherapies. This partnership reflects the growing role of our smart platform across both liquid and tissue and drug development and the strategic value of our platform to biopharma customers. We also made significant progress expanding both the scale and utility of our data sets through a series of high-impact partnerships. These collaborations integrate comprehensive EMR records who genomic and epigenomic tumor profiling to accelerate cancer therapy, research and development, advanced drug response prediction and biomarker insights using multimodal AI and enable biopharma partners to access EHR and clinical genomic data to support more efficient clinical development of new cancer therapies.

With that, I will now turn the call over to AmirAli for an update on screening.

Thanks, Helmy. Moving on to Slide 12. Shield has delivered extraordinary growth since launch. We delivered $35 million of field testing revenue in Q4 driven by approximately 38,000 tests, which was a meaningful step-up comfort to 24,000 tests in Q3. Revenue growth has closely tracked volume growth, reflecting ADLT pricing, favorable collections and a disciplined focus on reimbursable lives. Based on performance to date, we believe Shield is the most successful diagnostic launch in history outside of COVID testing is positioned to be a significant multiyear growth driver for Guardant.

Now turning to Slide 13 to take a closer look at streaming highlights for the fourth quarter of 2025. Shield had strong sequential growth in Q4 driven by growing demand from both patients and physicians. Assurance rates remained high, reinforcing the accessibility and convenience of blood-based screening to support the growing demand, we continue to scale our commercial organization throughout 2025, exiting the year with approximately 300 sales reps. Last month, we received coverage from TriCare for active beauty service members on their foundries with no copay. TriCare will cover Shield for all eligible average-risk individuals aged 45 and older. In Q4, we launched a dedicated health systems team, and we are excited to report that we have successfully deployed our first enterprise scale integrations with large health systems in West Virginia and Georgia. We are excited by the early progress demonstrating the market demand and our ability to operationalize field-leading complex health systems, including full EMR integration and workflow deployment. Beyond CRC, we are excited to expand Shield to include multi-cancer detection results reported in October. Although still early days, we are encouraged with physicians' enthusiasm to get access to MCD findings and strong interest by patients to be part of the MCD data collection initiatives.

Turning to Slide 14. We are very encouraged by Shields RealWorld adherence, which reached 93% across the first 100,000 Shield test order. In other words, when physicians order Shield for CRC screening, 93% of patients completed the test. This represents a meaningful improvement compared to other screening modalities, where adherence particularly ranges from 25% to 31%. As we illustrated in the patient's story earlier, the ability to complete the field test during an office visit removes key barriers and enables far more patients to complete their CRC screening.

Taking a closer look at our recent strategic collaborations to scare our pharmacal infrastructure on Slide 15. We are excited to announce collaborations with Quest Diagnostics and PathGroup, which will broaden our national reach in 2026. Our collaboration with Quest enables access to their national sales organization and allows providers to order Shield and receive results directly through the Quest connectivity system, which was used by approximately 650,000 clinicians on hospital accounts last year. We remain on track to launch this collaboration later this quarter. The pass-through for operation went live in the fourth quarter and expand Shield's bridge to more than 250 health systems at our 25 states. We look forward to seeing the positive impact of our growing commercial infrastructure in 2026 and and years to come.

Moving on to Slide 16. Our goal has always been to detect many cancer types early when they are most treatable. With that in mind, we developed Shield as a multi-cancer detection platform.

Turning to Slide 17. In fourth quarter, we expanded Shield to include a multi-cancer results report, which includes finding for 9 of the most common cancers in addition to CRC. With each positive MCD funding, the report includes a cancer site of origin or CSO color, which provides tumor-specific information giving more clear guidance to physicians for subsequent diagnostic workup. The [ SCD ] report is available to shield CRC patients who opt in and authorize the release of their medical data to Guardant. As a result of this initiative, we expect our Shield data repository to grow exponentially, and we look forward to leveraging this high policy data to support reimbursement and regulatory approvals drive a deeper understanding of clinical utility and support future technology improvements. We are enforced to see the recent passage of legislation establishing a Medicare coverage pathway for multi-cancer detection tests. While this is not expected to be a meaningful driver of our business in the near term, we view this as a positive step forward for the field.

Turning to Slide 18. We our outstanding commercial performance in 2025 reflected in rapidly growing revenue was driven by several factors. We had ADLT status for Shield securing at $1,495 reimbursement rate that supports healthy ASP and gross profit, enabling us to reinvest in commercial expansion. We also benefited from meaningful first mover advantage and clear product market fit which drove broad provider adoption, our best-in-class commercial execution continued progress through MR integration, inclusion in NCCN guidelines, where additional key contributors to our growth trajectory in 2025. We believe these foundational achievements position Shield for continued strong growth ahead. Looking more closely at our 2026 setup. The ADLT rate of $1,495 has now been incorporated into the clinical lab fee schedule and is secured to December 2027. We also expect to see benefits from our collaboration with Quest and PathGroup alongside to continue the expansion of our field force throughout the year. Additional growth drivers include ACS guideline inclusion, targeted direct-to-consumer campaign launches and the expansion of self-pace Shield into select markets outside the U.S.

Turning to Slide 19. We continue to invest aggressively in R&D to improve our product performance. As part of that process, we have rigorously evaluated dozens of external technologies over the years. We recently completed the acquisition of MetaSight Diagnostics, which brings a new technology once that is complementary to the smart platform and also brings on an impressive team further strengthening our world-class R&D organization. We are excited for the technology's potential to enhance our CRC screening, multi-cancer detection and ultimately, the entirety of our oncology product portfolio. It also has the potential to accelerate our multi-disease detection pipeline.

With that, I will now turn the call over to Mike for more detail on our financials.

Thanks, AmirAli. Turning to Slide 20. I'll review select financial highlights for the quarter and full year ended December 31, 2025. Unless otherwise noted, all growth rates are year-over-year Total revenue in the fourth quarter increased 39% to $281.3 million, reflecting strong execution across oncology, biopharma and data and screening. Oncology revenue increased 30% to $189.9 million driven by continued strong volume growth. We reported approximately 79,000 oncology tests in Q4 of 38%, demonstrating sustained momentum across the portfolio. Guardant360 Liquid volumes increased nearly 30%, supported by expanding clinical utility from Smart apps launched over the past year, and Guardant360 Tissue remains strong following the major upgrade introduced in Q2. Reveal continues to be our fastest-growing oncology product, benefiting from CRC to balance reimbursement and ongoing strength in breast and lung cancer. We were also encouraged by the early uptake of Reveal for late-stage therapy response monitoring launched in Q4. Average selling prices were stable sequentially, with Guardant360 Liquid in the range of $3,000 to $3,100. Guardant360 Tissue approximately $2,000 and Reveal between $600 and $700. As a reminder, we've submitted data packages to MolDX for Medicare reimbursement covering MRD and both immunotherapy and chemotherapy response monitoring. Successful outcomes will provide upside to reveal ASP. Biopharma and data revenue was $54.0 million, up 9%, which was in line with our expectations. Screening revenue totaled $35.1 million from approximately 38,000 Shield tests. Shield ASP was approximately $850 consistent with expectations and reflecting our focus on Medicare-covered patients. As of period revenue totaled approximately $18 million for the fourth quarter of 2025, including approximately $3 million related to screening. This was in line with prior periods compared to approximately $17 million in both the third quarter of 2025 and the fourth quarter of 2024. For the full year, total revenue grew 33% to $982.0 million. Oncology revenue increased 26% to $683.6 million. We reported approximately 276,000 oncology tests, representing 34% growth. Guardant360 volume growth accelerated to 25% for the year, driven by continued smart as production. Guardant360 Tissue volumes strengthened in the second half following the Smart platform upgrade and Reveal remained our fastest-growing oncology product throughout the year. Biopharma and data revenue grew 18% to $210.1 million. Finally, screening revenue totaled $79.7 million in our first full calendar year since launch, generated from approximately 87,000 Shield tests.

Turning to Slide 21. Non-GAAP gross margin improved to 66% in Q4 compared to 63% in the prior year. For the full year, non-GAAP gross margin increased to 66% or from 62% in 2024. This improvement was primarily driven by a significant reduction in Reveal cost per test which improved from over $1,000 in Q3 2024 to under $500 throughout 2025. We also made meaningful progress in improving share gross margins Shield's non-GAAP gross margin improved from negative levels at launch to 52% in Q4 2025. This reflects strong ASPs under the Medicare ADLT rate, disciplined focus on reimbursable testing and continued volume-driven cost reduction. Shield cost per test declined sequentially and exited the year at approximately $450 in line with our operational plan. Non-GAAP operating expenses were $260.0 million in Q4, up 21% and $903.7 million for the full year of 19%. Full year operating expense was modestly above guidance due to two Q4 items: firstly, an increase in accrual for the 2025 company bonus plan, which reflects a strong performance in the year across financial, regulatory and commercial milestones. Secondly, the continued reinvestment of incremental screening gross profit into sales and marketing to accelerate our commercial build-out. Adjusted EBITDA loss improved to $64.9 million in Q4 compared to $78.4 million in the prior year quarter. For the full year, adjusted EBITDA loss improved to $220.9 million versus $257.5 million in 2024.

Turning to Slide 22. We continue to improve cash performance in 2025. Free cash flow burn was $233 million for the year, an improvement of $42 million and in line with our guidance. Importantly, excluding screening, the core business generated positive free cash flow in both Q3 and Q4. We expect the core business to be free cash flow positive for the full year 2026 and and remain committed to achieving company-wide cash flow breakeven by the end of 2027. As AmirAli mentioned, in December, we acquired MetaSight for $59 million in upfront cash plus up to $90 million in contingent consideration tied to future commercial and regulatory milestones. We believe this technology enhances our existing product portfolio and accelerate our multi-disease infection pipeline. Following the MetaSight acquisition and our November equity and convertible debt financing, we ended the year with approximately $1.3 billion in cash, providing sufficient run rate to fund our growth initiatives and reach company-wide cash flow breakeven.

Turning to Slide 23. We entered 2026 with solid momentum across the business and increasing visibility to our growth drivers. For full year 2026, we expect revenue to be in the range of $1.25 billion to $1.28 billion, representing growth of 27% to 30%. This outlook reflects sustained strength in oncology and accelerating expansion in screening firmly positioning us to achieve our 2028 long-range revenue target of $2.2 billion. We expect oncology revenue growth of 25% to 27% in 2026, supported by volume growth of approximately 30%. We believe demand fundamentals remain strong across the portfolio. Guardant360 Liquid should continue to benefit from reduction of smart apps and Guardant360 Tissue growth should continue to build on the smart platform upgrade and continued strong commercial execution. Reveal is expected to remain our fastest-growing oncology product, driven by MRD and therapy monitoring. Note that our oncology guidance does not include potential upsides during the year from SERENA-6 ESR1 monitoring, FDA approval of Guardant360 Liquid CDx and the launch of Reveal Ultra. For biopharma and data, we're encouraged by recent strategic partnerships and the strength of our CDx pipeline. For 2026, we're forecasting low double-digit revenue growth supported by both ongoing collaborations and new program starts. We expect screening revenue to be in the range of $162 million to $174 million, driven by 210,000 to 225,000 tests, a meaningful growth from approximately $8 million revenue and 87,000 tests in 2025.

As in 2025, we expect a sequential increase in shield volumes every quarter, with the increases expected to be greater towards the back half of the year. This reflects earlier seasonality at PCP offices. The ramping productivity of our growing number of sales reps and the expansion of EMR capability to our Quest and PathGroup collaborations. Note that our screening guidance does not include potential upside from Quest co-promotion activities as well as ACS guideline inclusion, which we continue to expect in the near future.

We continue to make steady progress improving gross margins across our products through ASP optimization, workflow efficiencies, transition to NovaSeq X and disciplined cost management. For 2026, we expect non-GAAP gross margin to be in the range of 64% to 65%, reflecting ongoing operational improvements, volume growth and expected product mix. We expect non-GAAP operating expenses of $1.03 billion to $1.05 billion, representing 14% to 16% growth year-over-year. We anticipate continued operating leverage as revenue growth outpaces expense growth. R&D and G&A are expected again to remain relatively stable with incremental investments primarily directed towards screening sales and marketing. Finally, we remain focused on reducing cash burn each year. For 2026, we expect free cash flow burn of $185 million to $195 million, an improvement from 2025. Excluding screening, we expect the remainder of the business to be free cash flow positive for the full year.

Finally, turning to Slide 24. Looking ahead, we have a rich set of catalysts across our business that will drive continued growth. In oncology, we expect to have several new products including Guardant360 Liquid CDx following FDA approval, our ESR 1 monitoring test and Reveal Ultra. In addition, we expect to release additional apps driven by our smart platform and advanced reimbursement across multiple indications for Reveal. In biopharma and data, we expect new CDx approvals as well as additional strategic biopharma and Infinity AI data partnerships. In screening, we look forward to inclusion in ACS guidelines in the near future, driving commercial expansion with Quest and expanding self-pay shield outside the U.S.

With that, we'll now open the call for questions.

[Operator Instructions] The first question comes from the line of Dan Leonard with UBS.

I'd like to talk a little bit about Reveal therapeutic monitoring. Helmy, both you and Mike commented on that in your prepared remarks. Could you elaborate further on how you're framing that opportunity, both for reveal volumes as well as for Guardant360 volumes as well?

Yes. We're very excited about Reveal for therapy monitoring. We think it's important opportunity to really solidify and work synergistically with Guardant360. If you think about it, all the volume we have with 360 patients are being tested in terms of therapy selection and then this idea of coupling that with reveals for essentially monitoring how those patients are doing on therapies is really exciting. And then the nice thing about that is and fortunately, as some of those patients progress, they're going to need a new therapeutic decision in terms of hopefully a next-generation drug or a next line therapy that can be applied to them. And so Reveal for therapy monitory bridges to that next Guardant360 test. And we have a very unique platform and portfolio that allows these tests to work together. And so I would say that when we get some of the reimbursement wins for IO monitoring and chemo monitoring. This could be a very important driver for growth over the next few years for the oncology business.

The next question comes from the line of Puneet Souda with Leerink Partners.

The first one, Helmy, for you. When you look at the strong growth that you've seen in oncology, maybe could you elaborate how should we think about that throughout the year and both in G360 versus reveal how should we think about the growth of those products because important drivers like the camizestrant launch and other things that you mentioned are actually still not in the guide. So just trying to think about sort of how should we think about both of these products volume growth throughout the year.

Yes, maybe I'll start and then let Mike sort of jump in. No, we're very bullish about '26 in terms of the progress we've made in '25, and what we're seeing at the beginning of the year here. So I would say that we think it's going to be another strong year for 360, something around at least 20% growth in terms of volumes. And then obviously, another very strong year for Reveal. It will continue to be our fastest growing product. We think we'll see some acceleration, obviously, with reveal for therapy monitoring as well on top of that. So I think we're well underway for sort of Investor Day projections in 2028.

Yes. Well, maybe just to add because in back to you. I think in the back half of '25, we saw a nice acceleration with Guardant360 Tissue following the Smart upgrades that we did back in May of last year. So I think that also as we look forward in 2026, we continue to expect tissue to accelerate. We think there's getting the FDA approval for Guardant360 during the also could potentially have a pull-through impact on Guardant360 Tissue as well. So yes, we're really bullish about all of the products across oncology.

The next question comes from the line of Doug Schenkel with Wolf Research.

Both on Shield and they're related, it's really great to hear that you are expecting to be free cash flow positive in 2026, excluding Shield. I'm curious what you're thinking in terms of Shield specific burn. I think you've provided color on that in the past and I guess kind of building off of that. I believe you exited 2025 with approximately 300 Shield focused reps. How should we be thinking about the pacing of rep hiring throughout 2026? And where do you think the sales force should be at year-end.

[indiscernible] ope for the company was $233 million of that, roughly around $220 million was screening. We sort of set a target of $200 million to $300 million. Actually, we pushed quite hard on that, particularly towards the end of the year. We're really wanting to take advantage of our first mover position. And we mentioned again on the call that excluding the screening, the rest of the business was actually cash flow -- free cash flow positive for Q3 and Q4. For '26, we think a similar level of burn on screening is '25. So around that sort of $220 million mark. Again, we're going to be making heavy investments on the commercial side, really building out that infrastructure. We still expect '26 to be a year of investment for screening and then '27 to be a year of inflexion, where we start to get a lot of operating leverage on that commercial prescription that we and maybe just [indiscernible] one of the things, again, we set full company free cash flow guidance, $185 million to $195 million. So that's implying that the rest of the business now is strongly cash flow positive in 2026 as a senior guidance around $30 million positive cash flow. So yes, we're feeling really good about how we're sort of managing the [indiscernible].

In terms of commercial infrastructure and field force, we are very excited with a very powerful commercial platform that we built in 2025. And we are going to continue to build out that commercial organization in 2026. I'm not going to get into the specifics of maybe exact headcount of the field force, but maybe just to give you some direction and color the way that you can think about it. We will continue to invest our incremental gross profit that we are going to generate this year into further build-out of our commerce holding restructure on both sales and marketing and majority would go still in building sales force and hiring more people.

The next question comes from the line of Tycho Peterson with Jefferies.

I want to start off on one of the bigger topics on ADLT pricing. What is your latest thinking? And what have you baked into the guide if anything, for G360? And then overall, you are guiding for a decel in volumes and revenue in oncology, presumably some conservatism there. There's a lot you didn't bake in, but where do you think kind of the most conservatism is in the outlook on oncology?

Yes. In terms of ADLT, I think we're still on track in terms of our FDA submission, making very good progress there. We think that hopefully gets to the finish line in the second half of this year. And then potentially sets up second sort of next ADLT pricing rate for 360 at the beginning of '27. So nothing is baked in terms of ADLT pricing for 360 for 2026. In terms of the second part of your question, I'll let...

Yes, yes. I mean maybe on the volumes, '25 was an incredibly strong year, particularly with Guardant360 just with the Smart taps driving the volume. I think when we look at 2026 as just continuing that trend. Our our guide is 30% oncology volume growth. And so we think that's incredibly strong. And again, that's coming across all of the portfolio. How we mentioned it earlier, but we still expect strong traction with Guardant360. We well being the fastest-growing product and tissue continuing to accelerate. So Yes, I think we're feeling really positive about the guide that we put out for [indiscernible].

Okay. Mike, and then just a follow-up on speaking of conservatism, you're also guiding for Shield ASPs to be down relative to where you exited '25. What's the thought process there? And also what are you baking in for international? I know you flagged that as incremental?

Yes. On Shield ASP, we've seen this trend over the past few quarters. We're really focused on the Medicare population and reimbursable tests. And I think we've done a really great job there. But there is, we are seeing a lot of demand from the under 65. And so I think our assumption going into '26 is that, that demand will continue to grow. And that sort of mix of commercial versus Medicare is just going to increase. So that's really the fundamentals of obviously the ASP [ move it. ] We still -- we'll maintain the ADLT rate at $14.95. That's now going to be replaced with '26 and '27. And we're seeing great reimbursement from Medicare Advantage payers saying that's been leading to some hour period true-ups as well. And our ASP for Medicare basis getting stronger and stronger. But yes, it's just really going to be -- it's a mix impact between Medicare and non-Medicare. And on the international side, if the question was focused on on Shield, we've seen a small contribution from Abu Dhabi in '25. I think we expect again the international contribution to be relatively small in '26. And really the driver of the vast majority of the volume and the volume growth is going to come from the U.S. in '26.

The next question comes from the line of Daniel Markowitz with Evercore ISI.

I wanted to ask on Reveal Ultra. It sounds like that's an area where there's a lot of excitement internally. Can you talk a bit about what will be differentiated about the offering? How you see the tumor informed competitive landscape evolving? And when we can expect to see some data or a more substantial update on that asset?

Yes. We're excited about Reveal Ultra, making good progress there. We're on track for launching it this year. And it's something where we believe that the true clinical sensitivity of that test will be best-in-class. I think there's a lot of, I would say, contrived messaging in the space in terms of different bars that people are using, but we believe that this will, I think, redefine sensitivity the tumor informed space. There are other features of the test. It's going to do more than, I think, other tumor-informed offerings. We always have a special sauce at Guardant with all our tests in terms of when we launch them. And so I think I would just say stay tuned as we share more details later this year about that test.

The next question comes from the line of Andrew Brackmann with William Blair.

Amir, you sort of talked about the recent NFE legislation and sort of the longer-term impact there. Can you maybe just sort of broaden out that commentary, talk to us sort of about the importance there for Shield in particular. And as you sort of think about the necessary steps for Guardant to sort of take advantage of that, can you just remind us on sort of the data generation and sort of path to FDA approval here?

Yes. So as I'm talking about this MSA deal that just passed. So we are -- as I mentioned in the prepared remarks, your encouraged to see the passage of the legislation. It's moving the whole field forward, but it's not going to be a meaningful driver of our business based on the business plan that we have in near term. I can't exclude for the field, maybe as we go through midterm, and talking about more than tri-annual testing with Shield, maybe there would be operational to enable with this MSA deal for us. But again, in near term, we don't look at it as a meaningful driver of our business.

[Audio gap]

Submit something to the TAM approval. I know it doesn't land the cold story, but just trying to figure out as we think about upside.

Yes. Thanks for this important question. When we are thinking about the data that now we are generating with this NCD offering shield when the physician patients are opting in. On one side, we are really encouraged by the enthusiasm that we are seeing on the provider side and participation by patients to opt in to release their medical record to us. On the other side, on the data side, I think in hopefully, in near future, we would be the company that has access to the widest, broadest clinical data in terms of clinical utility of MCD testing in U.S. patient population. So if you're seeing good adoption rate. I don't want to get to the exact number of it. It's trending up, but so far so good. So far, so good, and we are very excited with it.

The next question comes from the line of Michael Ryskin with Bank of America.

This is Aaron on for Mike. Can you talk a little bit more about the puts and takes of the Shield guide? Obviously, 4Q saw the 4,000 in sequential volume growth, but should we think about thinking about that as more of an anomaly and just kind of thinking about how much conservatism is embedded within the guide? And I guess the second part of that is thinking about Quest and PathGroup, those look like upsides to the guidance. And so how should we be thinking about the timing of those impacts of those tailwinds as we head through the year?

Yes, sure. Look, Obviously, we are very excited with this guide of like 87,000 volume going to midpoint of $217,000 and a very huge revenue growth and contribution. On the other side, when you are saying about the guide. We are, again, just in the still very early inning of this launch. This is just a second year of launch, and we want to be thoughtful with our guidance. We typically don't want to get too excited and get ahead of our skis just based on one quarter performance. But the trends are very positive. We are, again, very excited of how 2026 is going to shape out for us. In the prepared remarks, you talked about some of the 1Q seasonality and PCP offices, it's kind of normal. For us, again, in terms of year-over-year growth for us. I think we are very excited with the guide that we put out there. And there are some upside you'll see like we are very optimistic about the ACS guideline, and we believe it should be nearer. It's not part of our guide right now until they update their guidelines. Quest, PathGroup very minor contribution. We are counting on some benefit of the EMR connectivity enabled through this Quest and pass-through integration but we are not counting any kind of contribution in terms of the volume contribution of the co-promotion and volume that comes from Quest sales people. We are going to monitor it. It should be positive. But since we don't know exactly how positive this would be, we want to monitor for the first few months of the launch and see how it goes. And then if appropriate, we would adjust our guidance accordingly. But we just want to be thoughtful about that matter as well.

The next question comes from the line of Mark Massaro with BTIG.

I wanted to also ask about Shield. So merely, One of the success stories of one of the drivers of the success of Cologuard was their direct-to-consumer TV launch. How are you thinking about spending in 2026. Is it more select digital? Or do you anticipate some spend on TV? And then I also wanted to ask about Quest. There is access for the, I believe, the Quest salespeople to promote Shield. I just want to double check that these reps are incentivized? And then can you just maybe give us a sense for where the Shield test might sit in their bag relative to the other products they're selling?

Yes. So some DTC pilot has actually happened for us in 2025 in select markets. And in 2026, we are excited that hopefully, consumers and even physicians would see even more of that. So we have some active campaigns that they are about to get finalized, and we are excited to put it out there and see what the impact would be. So we are very excited about it. The rest stay tuned after we launch it in very near future. In terms of Quest, yes, actually, the salespeople are incentivized. It's part of their commission plan. And what we do know is actually, it was very important and interesting for the Quest management team to get access to Shield as a very differentiated brand that gives them opportunity to talk about something new and something excited exciting with the accounts. So again, we are going to monitor how the launch goes with Quest in terms of core promotion part of it. It should be again positive, but we'll see how positive it would be.

The next question comes from the line of Kyle Mikson with Canaccord.

On the MetaSight acquisition, interesting to see that. Most of the consideration is tied to future commercial performance and the regulatory approval of the technology. So first one, wondering what the pathway is in non-cancer launches? And then second, it seems like the mass spec, how does that factor your NGS heavy platform.

Yes. So we are very actually excited about this acquisition to bring very high-quality world experts on some specific complementary technologies to our smart platform. So we are very excited to go to work and see what we can do. It's a small technology talking again. So let us make more progress, and we will talk about it at the right time.

The next question comes from the line of Casey Woodring with JPMorgan.

Great. Just a couple more on Shield maybe. So you mentioned that the guidance back half weighted. What is that guidance for Shield in 1Q? I think that, that comment would imply a sizable step down sequentially? And then I guess on the ACS commentary you made, if that hits in the first half of 2026. Can you help us think about the upside to volumes in the back half of the year and what that could look like?

Yes. Maybe I'll start with the ACS part. Let us actually see when it would happen, it should be in near future. But I think when you think about our dozen states that they have state-level mandates that even younger patient population should get access to the test. And the whole screening market is maybe about 40% of this 65 year and above and more are, in fact, on the younger patient side, that could be an interesting upside and growth driver for us once we start really going much deeper on the commercial testing within those states. But let's first see actually when they update their guideline we go from there. In terms of Q1, yes, that's true that there is some Q1 seasonality and PCP offices, which in terms of screening and so forth. But our team has done a very good job to reschedule appointments that have been kind of impacted with the events that have been impacted, and we are on track to screen more patients in Q1 than in any other previous quarters post launch. So let's see how the rest of the quarter goes, but Andrew will talk about it in our next earnings call.

The next question comes from the line of Dan Arias with Stifel.

This is Paul on for Dan. I guess I just want to follow up on Subu's question about kind of regulatory strategy for multi-cancer shield. One of your competitors had some data out this afternoon with not meeting the primary endpoint with a very, very large MCED trial in terms of looking for stage shift? And then one other piece was this week in the New England Journal, there was some FDA willingness to be a little more flexible on what evidence generation might look like? I'm just wondering if any of these developments kind of influence what you would look to do for your evidence generation strategy and for your regulatory strategy with Shield MCD?

Actually, this news just came out. So I don't know all the details of it. We'd be on this call with you guys. But I think when I think about really what is important in the field of multi-cancer detection is the performance of detecting early stages. And we believe with the technology that we have for Shield the performance of early stage detection as it's shown in CRC could be very interesting, and that could have a meaningful impact. On the other side, I think it really highlights what we are doing to capture all the clinical evidence, medical record of the patients who are going through MCD testing in U.S. and really establish the utility of this MCD testing at very large scale, we are going to benefit from this commercial scale of Shield, and we kind of put that evidence together in a very OpEx friendly and a very quick way. So I think it's kind of -- you're getting more bullish with the pathway that we went after screening business and what we are doing with our MSA.

The next question comes from the line of Luke Sergott with Barclays.

On the Shield demand and after you guys have had this for 1.5 years now, but this is like first full year launch has been great. you're going to trend even further for next year. Can you kind of give us a sense of where the demand is coming from? Like how much of this is from the care gap closure versus winning share from colonoscopy or FIT or Cologuard or any of the other tests?

Yes, the demand is coming from PCC physician in terms of patient types. Still, we are really focused on the screen patient population. I think some of the latest data that I've seen about still 90% of the patients who are getting screened by shield have not been screened before, at least during the last 5 years when we got access to their medical record and claims. So really, our messaging is working, and we are increasing the rate of overall screening. Care Gap and those kind of opportunities still is ahead of us. We need to get into -- we need to qualify for quality scores and Shield still is not once we get to the [indiscernible], that would be a huge additional growth driver for us. So Care Gap program is not part of our growth right now.

The next question comes from the line of Jack Meehan with Nephron Research.

I appreciate all the color on the screening investments you're making was wondering if you could share color on the oncology side, specifically, just the mark-to-market, how large the sales force is there now and planned investments? And then second, you've talked about the NovaSeq X transition, when in the years that taking place? And any way you can quantify level of savings you expect?

Yes. I think obviously, as Mike said, we reached cash flow positivity on the oncology side last year. And obviously, we'll be generating cash this year. We're in a really good spot in terms of where we are with oncology. We've been essentially reinvesting in the business as a matter of course, as we see opportunities for growth on the sales side as we see the revenue per rep to sort of grow. We saw tooth around a healthy number in terms of a matter, of course, expansion of the team. And so we're healthy spot, and we'll continue to sort of invest where we see return on investment in terms of potential volume growth. In terms of the NovaSeq transition, maybe I'll let Mike take that one.

Yes. We -- I mean, first of all, we've successfully transitioned to reveal the [indiscernible] just about just several years ago as well as workflow efficiencies. We saw a nice reduction in the cost per test of reveal. And with Guardant360, we started that transition. It will take time to fully be implemented, probably around about the middle of the year, I would expect total Guardant360 Liquid test to be on NovaSeq. And yes, we expect to see a nice improvement in our cost per test. I think just putting to quantify it a little bit, our gross margin currently for Guardant360 in -- within the high 60s, and probably once we've gone through the move to NovaSeq X and things are working properly, they expect to see maybe 200 basis point improvement and sort of pushing that Guardant360 gross margins into the low 70% level. So yes, no, we're we're feeling very positive about the switch, and it's going to have a nice impact on our P&L.

Our last question comes from the line of Bill Bonello with Craig-Hallum.

Thanks a lot for hanging on and taking another question. So one, I guess, is probably for Helmy. I think the -- if I understand it right, the FDA approval would open the door to physicians being able to order both tissue and blood from Guardant concurrently. I'm just curious what your sense of is for the appetite for using both tests upfront and then also touch on maybe any reimbursement challenges that you might anticipate if that becomes more common.

Yes. As you know, guidelines, I think, is -- are increasingly recommending that for patients upfront, especially in lung cancer and breast cancer, which are some of our two largest indications for 360. And one of the challenges is the way that LVT is reimbursed. It really is not possible to order them concurrently. And so that's obviously been a little bit of a headwind that sort of will become a tailwind once we get FDA approval for Guardant360. So we do see that as a potential driver obviously. We want to make sure it's done in the cases where it's there's clinical utility for the patients and value for treatment selection. But we're very confident that I think will be, I think, important catalyst for our tissue business going forward.

In the interest of time, that was our last question. That will conclude today's call. Thank you for your participation, and enjoy the rest of your day.

All right. Great. I think we can get started here. Hi, everybody. My name is Casey Woodring from the Life Science Tools and Diagnostics team here at JPMorgan. Pleased to introduce Guardant Health and the management team of -- at Guardant Health here. We're going to do a presentation followed by Q&A afterwards. Help me take it away.

Awesome. Thank you, Casey, and good afternoon, everyone, and thank you for joining us today. Please note our forward-looking statement. At Guardant, everything we do is guided by a simple but ambitious mission to give every person more time free from disease. We began that mission over 10 years ago pioneering the first liquid biopsy test for cancer therapy selection through countless innovations and we have expanded to help even more patients with their offerings for recurrence monitoring and cancer screening. To date, we have tested over 1 million patients, and our tests have been ordered by over 12,000 oncologists and thousands of primary care physicians.

Along the way, we've built a world-class commercial organization invested approximately $2 billion in R&D to deliver a steady cadence of category-defining products and established Guardant as a leader in liquid biopsy. And yet we believe we are still just getting started.

I'd like to begin with a patient story that illustrates the real-world impact of our tests. In 2014, Sara was diagnosed with HR-positive HER2-negative breast cancer. She underwent chemotherapy and remained cancer-free for more than a decade. As part of our monitoring in late 2025, she received a Guardant Reveal test which was positive for ctDNA and provided early evidence of recurrence well before it could have been identified through other methods. Because our tests are all built on the same platform, the physician could simply request a Guardant360 test from the same blood draw, which identified multiple actionable biomarkers, enabling her physician to quickly initiate a targeted therapy. This example highlights the power of blood-based -- our blood-based testing approach by detecting disease recurrence earlier and delivering actionable molecular insights from a single blood draw, our platform helps quickly guide treatment decisions across the entire cancer journey.

As demonstrated from this example, our tests are designed to work together as a single integrated platform. Today, Guardant is the only liquid biopsy company with offerings that span late-stage cancer therapy selection across both liquid and tissue, MRD and early cancer detection. Our product portfolio is now powered by our Smart platform, which goes far beyond genomics to unlock multimodal biology with proprietary chemistry, advanced algorithms and AI using our Infinity AI learning engine. This platform is key to our differentiated product portfolio and a robust pipeline of future growth drivers.

Turning to our recent performance. 2025 was truly an outstanding year for Guardant. We delivered $280 million of revenue in the fourth quarter, representing 39% year-over-year growth and $981 million of revenue or 33% year-over-year growth for the full year. Importantly, this performance didn't happen overnight. It built on several years of consistent strong growth. What's notable in 2025 is that growth continued to accelerate which reflects multiple engines across our portfolio. One, strong new product introductions in advanced cancer, meaningful reimbursement progress with the reveal and continued strong adoption of Shield in early detection. This broad-based momentum driven by execution gives us confidence as we continue to scale the business. We delivered on many major milestones in 2025 and -- in oncology, we made significant progress in therapy selection, including the launch of an upgraded Guardant360 tissue test and the introduction of multiple new smart applications.

We also continued the trend of improving financial execution, including increasing ASPs, expanding gross margins and tightly managing operating expenses. In MRD, we received reimbursement in CRC surveillance, which drove significant gross margin inflection and submitted our cancer -- breast cancer and therapy monitoring data packages to multi-X -- we established several strategic biopharma data partnerships that further strengthened our platform. And in screening, we obtained ADLT status, which improved our Medicare pricing, delivered positive gross margins, advanced our performance with GB2 data and shared compelling multi-cancer data.

Although the American Cancer Society did not update their guidelines last year, we are encouraged by their recent comments at the National Colorectal Cancer Roundtable meeting in November and expect an update in the near future. Our innovation engine is unlocking large new markets, and each breakthrough is building on the lab and enabling the next wave of higher-impact applications. Unlike most health care companies, our growth is not linear. -- it compounds through successive S curves, each dramatically expanding the value we deliver to patients, physicians and the health care system.

To date, we've unlocked 3 major S curves therapy selection, minimum residual disease monitoring and cancer screening. Looking ahead, shield is more than just a cancer test. It is the foundation of a multi-disease detection platform. We are encouraged by early signals that point to future growth in the $300 billion multi-disease screening opportunity. And with that, let's take a closer look at the oncology business.

Our oncology portfolio is built on our smart platform and addresses a combined opportunity of roughly $30 billion in the U.S. Liquid therapy selection alone comprises roughly 1 million advanced cancer patients and a $10 billion TAM as the field moves towards multiple tests per patient. Guardant360 liquid leads the market and continues to gain share a combination of product innovation and commercial execution. MOD comprises around 18 million patients, representing a TAM of $20 billion, with Guardant Reveal established as the leading tissue free solution in this space. Together, these represent some of the largest opportunities in oncology, and we believe Guardant is uniquely positioned to lead across the care continuum.

Smart platform innovation is translating directly into oncology volume growth. In 2025, oncology volumes accelerated to 276,000 tests, representing 34% year-over-year growth compared to 20% growth in 2024. That acceleration is being driven not by -- from a single driver, but by a few key factors. The first is a steady cadence of new Smart platform applications in Guardant360 liquid expanding clinical utility and adoption. Guardant360 grew nearly 30% in the fourth quarter and 25% for the full year, reflecting strong product market fit. At the same time, Reveal was our fastest-growing product given its clear leadership in the rapidly expanding tissue free MRD market.

And finally, we're seeing very strong traction with Guardant360 tissue following the smart platform upgrade and the addition of comprehensive RNA analysis. Through our Infinity AI learning engine, we are leveraging an expanding data treasury and the power of AI to uncover novel biological signatures and translate them into differentiated products. As our data repository continues to deepen with rapidly growing smart epigenetic profiles, multimodal longitudinal data and now data from earlier stage in asymptomatic patients through SHIELD, we are increasingly excited about the pipeline of products ahead. This data advantage fuels more than just clinical product development. It also is generating new therapeutic insights for our growing biopharma business and enabling commercial intelligence and decision support tools that strengthen our execution. And importantly, this is already delivering results. In a remarkably short amount of time, Infinity AI has powered the launch of over 15 smart apps with many, many more to come.

And now I'll show you how we're bringing AI directly into how results are delivered, creating a vastly simpler, more intuitive experience that helps physicians make better decisions and ultimately improves patients' outcomes. Today, I'm excited to introduce a new Infinity AI-powered clinical navigation experience. Within our portal, Infinity AI ingest data from across the care ecosystem, multiple garden tests, EMR data, pathology reports and other clinical documents, including scanned and handwritten notes. Instead of asking physicians to sift through multiple reports, each 10 or 20 pages long Infinity AI brings everything together into a single longitudinal view of the patient spanning comprehensive profiling, therapy monitoring and progression. We then layer in treatment history, NCCN guidelines, and so clinicians can see clear context and relevant options, not just raw results. And we help guide what comes next, including therapy changes, ongoing monitoring and MRD after treatment begins. That's the power of Infinity AI, turning fragmented data into clear, actionable insight and giving physicians a simpler, smarter way to navigate increasingly complex cancer care.

In addition, we continue to build a deep and growing body of clinical evidence. Today, our technology is supported by more than 1,200 conference publications and abstracts and over 670 peer reviewed publications and a broad range of cancer types. Recently, we had a very strong presence at San Antonio Breast Cancer Symposium with 17 independent abstracts presented across our oncology portfolio.

Turning to MRD. We continue to make strong progress supported by robust clinical and reimbursement pipeline. Following our success in securing Medicare coverage for CRC surveillance, we recently submitted additional data packages to support coverage and breast cancer surveillance as well as IO and chemo monitoring and soon for CDK4/6 inhibitor monitoring. Looking ahead, we have multiple ongoing studies designed to support indication expansion for Guardant Reveal spanning both the adjuvant and surveillance settings.

Building on our leadership in tissue free MRD, we were excited to launch Guardant Reveal for therapy monitoring in the fourth quarter. Reveal therapy monitoring expands our tissue free solution into a large and totally new opportunity in late-stage cancer where there is a major unmet need. Rather than waiting for radiographic scans, physicians can now use a simple blood test to gain a real-time molecular review to assess treatment response and to detect disease progression earlier with unprecedented speed and accuracy. When paired with Guardant360 liquid, this capability creates a seamless system to treat, monitor and retreat patients. While still early, we've been very encouraged by the strong initial traction we're seeing with the Reveal therapy monitoring and believe this will be a major growth driver for the Reveal franchise in the coming years.

We're also seeing promise of a new monitoring application for Guardant360 with the SERENA-6 trial. The AstraZeneca sponsored study evaluated progression-free survival benefit after switching late-stage breast cancer patients to chemezesterant after emergence of an ESR1 mutation was detected in the blood using Guardant360. Once Guardant360 is approved as a companion diagnostic, we believe this new practice-changing protocol could be a meaningful driver of Guardant360 volume in the future. This is a powerful demonstration of the future of cancer care, where therapy is swiftly guided by precise molecular signals rather than delayed by sometimes subjective imaging.

Beyond tissue free MRD, I'm excited to share an update on REVEAL Ultra our next-generation ultra sensitive tissue-informed MRD assay capable of achieving clinical sensitivity down to 1 part per million. As we shared at our Investor Day in September, Reveal Ultra is built on our smart platform and uniquely combines the strength of both our liquid and tissue technologies. This allows us to push well beyond what's possible with existing approaches. Let me put that into context. What you see here on the plot is the sensitivity ranges of current state-of-the-art tumor-informed MRD testing. Assay is built on detection of 16, 64 or in 256 tumor mutations often claim ultrasensitive detection. But in reality, those results are only achievable and contrived cell line samples with unrealistic amounts of input DNA. Even panels with 2,000-plus mutations improved sensitivity, but they still fall short of what is sometimes needed in routine clinical samples. Reveal Ultra moves the boundary of what's possible in terms of detection.

In a recent analysis of clinical cohorts across challenging tumor types Reveal Ultra consistently detected patient occurrences at levels approaching 1 part per million while maintaining 100% specificity. Importantly, a significant percentages of these recurrences were detected at levels well below 5 parts per million, levels that will be likely missed by existing and emerging tumor-informed MRD assays. That's the difference between theoretical claim sensitivity and true clinically meaningful detection. And today, I'm excited to announce that Guardant Reveal will be launched commercially for use in clinical MRD testing later this year.

Shifting gears to our industry-leading biopharma business, which has been a strong revenue contributor and is an important strategic asset for our business. We had strong performance once again in the biopharma business in 2025 with record revenue and contracted volumes, driven by the unique biological insights made available through our power of our Smart platform. We are a leader in companion diagnostics with 24 approvals to date across the U.S., Japan and Europe, with a strong pipeline of ongoing CDx programs. Our partnership with over 200 biopharma customers, including 19 of the top 20 companies is core to the strength we continue to experience. Last year, we established multiple global strategic partnerships with large pharma. We are encouraged by our continued traction in China, where the pipeline continues to grow rapidly, and we have more than 15 partners signed to date.

And with that, I'll turn it over to AmirAli to share more details on our screening business and to close out the presentation.

Thank you, Helmy. Now switching to our screening business where we are the market leader in blood-based CRC screening, just over 1 year into commercialization. We are still in very early stages of penetrating a very large unaddressed market. The opportunity is significant with a $50 billion colorectal cancer screening market and more than $54 million on screen patients in the U.S. alone. This scale underscores both the magnitude of the unmet need and the opportunity for Guardant to deliver meaningful clinical impact and long-term value. From the very beginning, our goal has been to identify and catch many cancer types early when they're most treatable. With that vision in mind. We built Shelfomground-up as a multi-cancer detection platform. We chose CRC as the first screening application. Because of the attractive balance between the market opportunity and the unmet need to close the gap in CRC screening while still having a clearly established regulatory and reimbursement pathway which helps facilitate broad patient access to this life-saving test.

Shield has delivered exceptional growth since launch. In Q4, we delivered approximately 38,000 shield tests, representing a meaningful step-up versus 24,000 tests in third quarter. Revenue has grown commensurate with volume growth and volume strength as ADLT pricing and a disciplined focus on reimbursable lives has translated into meaningful top line performance. With this strong performance this year, we believe Shield is the most successful diagnostic launch in history outside COVID testing and will be a significant multiyear growth driver for Guardant. Shield has strong and fundamental advantages to offer in the fight against cancer and is well positioned to be the leader in the early cancer detection. Shield is the first and only FDA-approved blood test for primary CRC screening. The blood modality easily integrates into the routine workflow of primary care offices and offers very high patient adherence.

Shield was developed by leveraging over a decade of investments and innovations in liquid biopsy at Guardant. This resulted in the best-in-class clinical performance in a pivotal study. The clinical impact of Shield is backed by broad clinical evidence, including randomized studies, which demonstrate that Shield can significantly reduce CRC screening gap. Moreover, our blood-based data repository is a powerful asset that has quickly grown to be the largest of its kind, paving the path for future advancements. And finally, the multi-cancer detection capability can broaden the clinical value in the fight against cancer.

We are very pleased with Shield's real-world adherence level, which was 93% across the first 100,000 patients tested meaning when the doctors are ordering Shielf for CRC screening, 90% of the patients, in fact, complete their tests. This is a significant improvement over other modalities with adherence rate ranging between 25% to 71%.

Now shifting into our commercial development. Throughout 2025, we expanded our commercial channel significantly and enter 2026 with a sales team of approximately 300 people. We are also excited to announce collaboration with Quest Diagnostics on Pad Group in 2025, which will broaden our national reach in 2026. The Quest Diagnostic collaboration is on track to launch this quarter. In addition to providing access to Quest national sales organization, providers will be able to order shield and receive results directly through the Quest diagnostic connectivity system used by approximately 650,000 clinicians and hospital accounts last year. The Pat group collaboration went live in the fourth quarter. and expand shield reach to more than 250 health systems across 25 states.

In addition to these collaborations, we continue to invest in scaling our commercial organization to efficiently capture this growing demand. To capture provider and patient attention, we are employing bold messaging across multiple channels, including TV, digital, direct mail and our influencer campaign. These messages are designed to drive awareness, improve education, ensure Shield is included in the consideration set when evaluating CRC screening options. Although we are in early days, the national media attention and third-party media scoring services suggest that these campaigns are performing well and generating positive return.

Our outstanding commercial performance in 2025 as evidenced by quickly ramping revenue for us was rooted in several key building blocks. We achieved ADLT status securing a reimbursement rate of $14.95 and providing strong ASP and gross profits to fuel aggressive investments behind scaling the commercial infrastructure. We have a first mover advantage and strong product market fit as evidenced by enthusiasm providers have shown in adopting shield, our commercial excellence, our commercial execution progress with EMR integration, inclusion in NCCN guidelines, all were additional major factors that drove strong performance for us in 2025.

Now turning to 2026. Very recently, our ADLT rate of 14.95 was included in the new clinical fee schedule and is confirmed for the next 2 years until December 2027. Our Medicare Advantage collection is going very well, and we expect to get our first commercial coverage in 2026. We are very much looking forward to additional growth drivers, which include continued expansion of our field force, ACS guideline inclusion launching our targeted DTC campaigns, Quest and Pat group collaboration. We are also planning to expand the self-base shield in select markets outside the United States.

Turning to Shield multi-cancer detection. In the fourth quarter, we expanded Shield to include a multi-cancer findings report, which includes finding for the 9 of the most common cancers in addition to CRC. With each positive MCD finding, the report includes a cancer site of origin or CSO color, which provides tumor specific information, giving more clear guidance to physicians for subsequent diagnostic workup. The Shield MCD report is available to shield CRC patients who opt in and authorized the release of their medical data to Guardant. In the first 3 months of shield expansion, including the MCD report, feedback on user experience has been very positive with strong interest by patients to be part of this MCD data collection initiative. As a result of this initiative, our Shield data repository is growing exponentially, and we look forward to leveraging this high-quality medical data to support reimbursement regulatory approvals driving a deeper understanding of clinical utility and support future technology improvements.

While we are focusing on oncology and cancer screening at this time, Shield is a platform that can expand well beyond oncology and cancer. We have already accumulated a robust database of epigenomic signatures in many diseases in asymptomatic individuals including liver disease, kidney cardiovascular, neurodegenerative and autoimmune diseases. We are excited about the strength of our pipeline and the vast opportunities ahead.

Now taking a closer look at our financials. We have a strong balance sheet following our recent financing and convertible restructuring and ended this year with approximately $1.3 billion of cash. In 2025 we continued the trend of improving our cash burn each year. Furthermore, excluding screening, we generated positive free cash flow in both Q3 and Q4 of 2025. As a reminder, at our Investor Day in September, we pulled forward our long-term profitability guidance by 1 year, and we now expect to be free cash flow breakeven in Q4 of 2027.

Looking ahead, we have a rich set of catalysts across our business that will drive continued growth. In oncology, we expect to launch several new products, including Guardant360 liquid following FDA approval, our ESR1 monitoring test, Reveal Ultra. In addition, we expect to release additional apps driven by our Smart platform and advanced reimbursement across multiple indications for review. In biopharma and data, we expect new CDx approvals, including SERNA6 as well as additional strategic biopharma and Infinity AI data partnerships.

In screening, we look forward to conclusion in ACS guidelines driving commercial expansion requests and expanding self-pace shield outside the U.S.

With that, I'll turn it back over to Casey for Q&A. Thank you.

So maybe to kick it off here, Garden preannounced the solid top line beat this morning Digging into the oncology performance here, you saw a 38% year-over-year test growth. Maybe walk us through performance. Did G360 volumes accelerate in the quarter again? How much of that growth was driven by REVEAL. It also seems like based on the volumes you reported, the ASP or maybe the biopharma segment maybe came in a little soft relative to expectations. So just can you unpack the quarter from an oncology standpoint?

Yes, I'll start, and then, Mike can feel in [indiscernible] off. Actually, very similar dynamics to Q3. We're very pleased with the performance we saw was Guardant360, as we said in the presentation, grew nearly 30% year-over-year, very strongly. Reveal was our fastest-growing product and tissue was in between. So almost exactly the same dynamics as as Q3 and pretty similar top line growth as well. Really no dynamics. Only difference is maybe some of the seasonality of number of days in Q4 versus a number of days in Q3.

Yes. Well, maybe just to add from the revenue perspective, and obviously, we're still finalizing the numbers, and so we're not breaking them out by the different segments. But Yes. I would say there's no surprises in the revenue numbers. The ASPs came in right in line with how we had expected, how we'd guided. Our biopharma business came in strongly again in Q4 and we ended pretty much in line with our guidance. So yes, no, it's a great finish for the year from us from a revenue perspective. We're really pleased with the performance.

Okay. And moving to screening, volumes stepped up there nicely, coming above our estimates in the quarter. Can you walk us through the mix of Medicare versus commercial patients and how this impacted ASPs? And it would also be helpful to hear about ordering trends and the mix of new physicians that are ordering versus going deeper into existing accounts?

Yes, still as because we are really focusing on reimbursable cases, the vast, vast majority of the samples that we are processing for Shield are coming from patients at 65 and above, which are fee-for-service beneficiaries within the medical baculo MA between those 2, it's kind of 50-50. In terms of the ordering physician, actually, we continue to see a very healthy and strong increasing breadth of ordering like we are adding a lot of each quarter. Having said that, we are just scratching the surface. There are about 250,000 HCPs ordering noninvasive CRC screenings. And still, we are just in very, very early innings of touching all those kind of physicians. .

Okay. Maybe as a follow-up to that, you launched in -- so curious how that contributed to the volume number for Shield in terms of the number of CRC tests that were run with MSAT attached.

Yes. So we have 1 shield test and when the physician patients are opting in. We are providing MSAT findings report to them if they are interested number that we are reporting are in fact the number of CRC cases that we are doing for a fraction, the MSAT was included. Still, we don't have 1 full quarter of data for this MSET attachment, but I can tell you the feedback from both physicians and patients has been very strong and very positive. So we'll see how it trends. .

Okay. And one last 1 on the preannouncement here, then we'll move on. Obviously, a very strong 2025 from a volume perspective with oncology testing growing 34% year-on-year. How should we think about the sustainability of that growth as we think about 2026. And then same thing on Shield. You're exiting the year with a 14,000-ish unit sequential step-up in volumes here. So is that an appropriate cadence for 2026 on a quarterly basis?

Yes. I guess I'll maybe just say that like I think we still stand behind our Investor Day sort of projections in terms of the CAGR over the next few years. And we have a really nice setup in terms of the oncology business, where we're still very much in the early innings of the smart apps that we've launched. There are many more smart apps that are coming. We have the catalyst of FDA approval, which we didn't talk much about with Guardant360 liquid that -- it's been a really catalyzed volume by really consolidating the portfolio. ESR1 obviously monitoring reveal for monitoring. We're seeing very good traction, I think, with some of those products initially. And Yes. And so -- and then obviously, tissue is still very much in its early innings and then we have Reveal Ultra as well. So we really don't have a dearth of growth drivers ahead of us. '26 should be a very strong year.

We are not providing guidance. We would do it at our 4Q earnings call, but Definitely, we are very excited with the exit momentum we are seeing on the shield and looking forward to see what happens in 2026. As Helmy mentioned, we are even more confident about the long-term targets that we put out there for 2028.

Maybe sticking with oncology. Garden has attributed the acceleration in G360 liquid volumes in part to the rollout of smart apps. If you had to pick the top 3 most impactful and well-received smart apps driving physician excitement, which would those be? And additionally, how much runway do you see for the most recent batch of applications to support sustained volume acceleration there?

Yes. I mean one of the -- ones that's been very exciting is the subtyping application, being able to see essentially the heterogeneity or the subtype of disease like lung cancer, you can see that it's small cell or non-small cell in breast cancer. You can see that it's triple negative or it's changing to HR positive, for instance. And so seeing really -- seeing that evolution over time and liquid has been really, I think, exciting to many physicians. We have another one for negative prediction. So being able to confidently call that sample is truly negative that there's sort of wild type for KRAS or that there truly is in a detected molecular alteration that could be actionable. And then I think pharmacogenomics has been really exciting. Being able to detect cancer of unknown primary and tell you what type of cancer it is. It's been really another compelling one. There's a surprising a larger population of sort of unknown primaries out there than people expect. And so that's resonated quite a bit. And yes, we have a cadence of dozens new apps that are in development as well, things like epi genotyping, being able to detect let's say, a fusion using methylation and not detecting it directly doing that with genomics. That is something that we'll be rolling out soon and some of the predictive apps being able to predict immunotherapy or cetuximab or CD4 K6 inhibitors using methylation is also on its way.

Okay. And then shifting to Reveal. Assuming Reveal received Medicare coverage for breast and I/O, how should we think about reveal ASPs exiting 2026? And would additional indications be needed to reach the long-term target of $10? Or would strong execution in breast and I/O just be sufficient?

Mike?

Yes. I think overall, if we get MolDx reimbursement for breast and in an -- we'll have a very strong uptick to our ASP. So yes, you mentioned it, our 2028 target is $1,000. For the last few quarters, we've been sort of $600 to $700 and that's really based of CRC reimbursement that we're getting. So I think if we get multi-x reimbursement and we pull through Medicare Advantage and we make some continued progress on the commercial side, then that should be getting us pretty near or at the 1,000 mark. That MA pull-through in commercial, it's going to take more than a year. So I wouldn't expect that at the end of at the end of '26. But I think if we're -- if we've got those reimbursement from MolDX, we're well on the way to $1,000. .

Okay. That's helpful. And then maybe just last 1 for oncology and help me then we can shift to screening. But now that the upgraded version of G360 tissue has been on the market for a few quarters, what trends are you seeing there? Can you provide any color on the attach rate with G360 liquid, what indications you're seeing the most traction in? And any competitive dynamics that are worth highlighting?

Yes, it's been very good. We've been very excited by the launch. We've seen very good traction since we launched it in the middle of the year. The dynamics in terms of tumor types actually closely follows what we see with the Guardant360 liquid. So lung is our #1, and it's simpler, like breast is #2. And so very similar to Guardant360 liquid I would say where we're seeing a lot of traction is the fact that we can use very, very limited amounts of samples so we can really successfully sort of sequence and report out these samples that tend to be QNS by other approaches. And so that has been the kind of like a very easy entry point for us into the market. And once physicians see the service, they see the report and the excitement there, then they the sort of transition onto the platform. I would say going forward, there's a whole host of smart apps that will be launching on tissue that I think will further catalyze volume. .

Helpful. Maybe AmirAli, you've discussed the future steady state CRC screening market where at least 20% of all patients will get tested through blood. How do you view the path to reaching the share? Where do you think share could exit 2026? And how might potential ACS guideline inclusion really accelerate that trajectory?

Yes. So we saw actually after NCCN guideline inclusion, a very nice kind of impact on the growth trajectory and conversations about Shield was positive, even became even more positive. So when you look at out of 120 million patients who are eligible for CRC screening, 54 million of that, as I mentioned in the presentation, are on screen. And there were other modalities in the market, some for 20 years, some for 10 years. And if we wanted to be able to screen those patients, we would have been better, have been able to screen them really in a very meaningful way. And we've seen in randomized studies that you add Shield as a choice, the rate of screening goes from 45% even to 90%. So that's the promise of adding blood as a choice. And I think, in fact, getting to 20% of the patients getting screened by blood is a very, very reasonable long-term target and all the catalysts like inclusion by guidelines, ACS, USPSTF and so forth would be drivers to get to our point help us to get to that goal.

Maybe in the last couple of minutes here. We touched on MSET earlier, but just curious to hear what the strategy is moving forward. particularly how you're going to use the data that you collect to support FDA submissions and any sort of timing on when we can expect those submissions?

It's very exciting. When you look at -- if the trends that we are seeing in Q4 continues for us, it's not going to take us long to have a database of 100,000 patients, U.S. patients that we have access to their medical record, and we've been testing them by Shield with MSAT result finding. And the value of that database in the real world is going to be very huge to figure out really the real world performance in terms of sensitivity, specificity of the Shield and the clinical value that it has offered potentially. So this exponential growth of Shield is going to go into the exponential growth of this database that we are capturing. We are very excited with that. .

Actually, 1 more sad -- what's the plan to introduce pricing here? Will you wait until CMS reimbursement established? Would you consider launching into the cash pay market and where other competitors sort of -- what's your thinking on pricing there?

So in U.S., actually, we are offering at this time, MSET result finding as part of our Shield, it's the same test effectively if the physician decides to get access to it and the patient opts in. In outside the U.S., we are looking into some kind of self-pay opportunities to offer multi-cancer detection capabilities of Shield as a self-pay opportunity, and we see what happens in some of the conversations, which are ongoing. As I mentioned, in our catalyst slide, we think 2026 would be an exciting year for Shell to expand our international business.

Okay. And then maybe last one, we have a minute here. How are you guys thinking about the strength of Guardant's balance sheet? What are your plans for capital deployment moving forward, including the potential for maybe smaller acquisitions to enhance Gardens tech platform?

Yes. I mean we're feeling very comfortable with the balance sheet. We did our equity and convertible financing in November. As we mentioned in the presentation, we ended the year with $1.3 billion in cash. And just to break that down a little bit more, $500 million of that is a mark to prefund our convertible that matures at the end of '27. So taking that aside, we've got $800 million in cash -- we're reducing our cash burn every year. We're on track to get to free cash flow breakeven by Q4 2027. So that $800 million is more than sufficient to get us there. So I think it actually gives us some firepower to look at small acquisitions. We've got a very active corporate development team. We do a lot of technology assessment. So if we identify the right technology that can help differentiate the products, generate -- help us drive revenue growth, then I think we feel in a position to be able to do that with the balance sheet that we've got.

Okay. Well, looks like we'll have to leave it there. Thank you for everybody for attending. Thank you to the Guardant Health team for joining. Enjoy the rest of the conference.

Good afternoon. Thank you for attending the Guardant Health Q3 2025 Earnings Call. My name is Cameron, and I'll be your moderator for today. [Operator Instructions]

And I would now like to pass the conference over to your host, Zarak Khurshid with Guardant Health. You may proceed.

Thank you. Earlier today, Guardant Health released financial results for the quarter ended September 30, 2025. Joining me today from Guardant are Helmy Eltoukhy, Co-CEO; AmirAli Talasaz, Co-CEO; and Mike Bell, Chief Financial Officer.

Before we begin, I'd like to remind you that during this call, management will make forward-looking statements within the meaning of federal securities laws. These statements involve material risks and uncertainties that could cause actual results or events to materially differ from those anticipated. This call will also include a discussion of non-GAAP financial measures, which are adjusted to exclude certain specified items, additional information regarding material risks and uncertainties as well as the non-GAAP financial reconciliation to most directly comparable GAAP financial measures are available in the press release Guardant issued today as well as in our 10-K and other filings with the SEC. Guardant disclaims any intention or obligation to update or revise financial projections and forward-looking statements, whether because of new information, future events or otherwise, except as required by law. The information in this conference call is accurate only as of the live broadcast.

With that, I would like to turn the call over to Helmy.

Thanks Zarak. Good afternoon and thank you for joining our third quarter 2025 earnings call.

Starting on Slide 3. Q3 was an exceptional quarter for Guardant with broad-based growth across our business. Oncology volumes grew 40% as year-over-year volume growth continued to accelerate driven by Guardant360 Liquid, Guardant360 Tissue, and Reveal. Our biopharma business grew nicely year over year with positive CDx momentum and screening volume accelerated with a sequential increase of 8,000 Shield tests. Importantly, screening has started to generate meaningful revenue tracking at an annual run rate of approximately $100 million roughly one year into the commercial launch of the FDA-approved product.

Overall, we are very pleased with our performance this quarter delivering 39% year-over-year revenue growth and crossing over $1 billion in annualized revenue for the first time. Excluding screening, we reached a major milestone with the rest of the business becoming cash flow positive one quarter earlier than expected. Indeed, this quarter sets us up very well to deliver on the long-term plan that we laid out at our Investor Day last month. Lastly, we recently surpassed 1 million cumulative clinical patients tested by Guardant and as such we want to highlight one of these patients with a story that captures the profound impact our tests are having in everyday clinical practice.

A 67-year-old man had gone unscreened for colorectal cancer for several years despite his physician offering colonoscopy or stool-based tests annually beginning in 2021. Each time the patient declined to be screened. In December 2024, the physician ordered a Shield blood test, and the patient agreed to complete the blood draw during the same visit. The result came back positive. When his physician explained that a positive Shield result required a follow-up colonoscopy, the patient agreed to have the procedure despite previously resisting. The colonoscopy was performed in January 2025 revealing colorectal cancer. The patient quickly began treatment, and at his most recent follow-up, he had successfully completed therapy and was doing well.

This is a powerful example of how the Shield blood test can remove barriers to screening, provide a more pleasant and convenient option for patients, and ultimately improve outcomes.

Now turning to top-line performance on Slide 4. Q3 revenue grew 39% year over year to $265 million with strong performance again across our oncology screening and biopharma and data businesses.

Taking a closer look at our oncology business on Slide 5. Oncology revenue increased 31% to $184 million and oncology volumes increased 40% year over year to approximately 74,000 tests in the third quarter.

Turning to Slide 6. We have seen a clear acceleration in volume since July of last year, following the introduction of Guardant360 Liquid on our Smart platform. Since then, we have launched 2 additional waves of applications, driving 5 consecutive quarters of accelerating volume growth and we look forward to future waves of Smart app introductions developed through the power of Infinity AI to help fuel future growth. In addition to Guardant360 Liquid, Guardant360 Tissue and Reveal volumes also experienced strong year-over-year growth.

Moving on to Slide 7. As a reminder, our Infinity AI learning engine applies AI across our data treasury of over 1 million patient samples, including more than 350,000 epigenetic profiles across more than 100 tumor types to bring powerful insights and new products to market faster than ever. Infinity AI enables higher resolution mapping of tumor biology giving rise to not only entirely new products in the clinical business, but novel signatures for faster drug discovery relevant to our biopharma business and new commercial insights and decision support tools.

Turning to Slide 8. To date, we’ve launched 15 groundbreaking Smart apps on Guardant360 Liquid with dozens more in development that we’ll roll out across Guardant360 Liquid, Tissue, and Reveal. Each new application builds towards what we see as a GPS for cancer care, guiding physicians with the right insights at every step of the patient journey. We believe these applications not only significantly expand the clinical utility of Guardant360 Liquid but further extend our technical leadership in the liquid CGP market.

Looking more closely at some of the recent highlights within our oncology business on Slide 9. Guardant360 volume grew exceptionally with more than 30% year-over-year growth. Guardant360 Tissue also had a great quarter showing strong year-over-year acceleration following the major product upgrades released in the second quarter. Once again, Reveal contributed very nicely and continues to be our fastest-growing oncology product.

In addition to the strong performance, we recently reached a major milestone with submission of our PMA application to the FDA for Guardant360 Liquid. This submission has the potential to streamline Guardant360 Liquid with a single flagship FDA-approved liquid biopsy for therapy selection, simplifying our portfolio, accelerating adoption, and further strengthening our leadership in this space. In addition, FDA approval would lay the foundation for ADLP designation which is an important mechanism for capturing the appropriate value for our expanded test offering in the future.

We had a strong presence at ESMO 2025, with 15 abstracts spanning the cancer care continuum, from MRD detection and recurrence monitoring with studies such as PEGASUS to advanced stage tumor profiling and therapy response assessment. For Reveal, we’re making great progress with data generation and publications. We recently submitted our immuno-oncology therapy monitoring data package to MolDx to support Medicare reimbursement and submitted data from our chemotherapy monitoring study for publication.

Turning to Slide 10 to take a closer look at our Reveal data pipeline. Over the last few months, we’ve made significant progress in MRD, generating and publishing compelling data across multiple cancer types. Earlier this year, we achieved Medicare coverage for CRC surveillance and have since submitted dossiers for breast surveillance as I just mentioned for immuno-oncology therapy monitoring. We plan to submit packages for chemotherapy and CDK4/6 inhibitor monitoring following those publications. Looking ahead, we have ongoing studies across more than 5 additional tumor types in both the adjuvant and surveillance settings. Together, this growing body of evidence will continue to strengthen the clinical utility and analytical validity of Reveal, supporting broader adoption in MRD.

Turning now to Slide 11. I am proud of the progress we have made over the last few years in both driving demand and revenue growth across our portfolio. Looking ahead, we see multiple drivers across our oncology business that position us well for durable long-term growth. We will continue investing in commercial initiatives that make it easier for physicians to access our tests through portal enhancements, EMR integrations, and enhanced workflows.

In our therapy selection business, transitioning to the Smart platform unlocks wave after wave of novel applications, many unique to Guardant that will help us differentiate and continue gaining market share. And in MRD, a redoubled commercial focus on Reveal supported by significantly lower COGS and Medicare coverage for CRC surveillance positions us for strong growth ahead. We’re also excited to introduce an Ultra-sensitive tissue-informed MRD assay that will complement our best-in-class tissue-free Reveal test.

Looking more closely at some of the recent highlights within our biopharma and data business in Slide 12. We delivered another strong quarter with third-quarter revenue growing 18% year over year. We continue to deepen our relationships with large pharma and had 2 additional companion diagnostic approvals in Q3. In late September, Guardant360 CDx received FDA approval as a companion diagnostic to Inluriyo for the treatment of ESR1 mutated advanced breast cancer. This marks the second FDA-approved indication in breast cancer and the sixth overall CDx claim approved by the FDA for Guardant360 CDx. We also received regulatory approval in Japan for Guardant360 CDx as a companion diagnostic to Enhertu for non-small cell lung cancer patients with HER2 mutations. We now have 23 total CDx approvals across biomarker and tumor types. Our robust and growing pipeline of partnerships ensures that near-term revenue visibility remains high.

With that, I will now turn the call over to AmirAli for an update on screening.

Thanks, Helmy.

Moving on to Slide 13. We delivered $24 million of Shield testing revenue in Q3, driven by approximately 24,000 tests. It's been incredibly rewarding to see Shield volume take off and hear story after story of patients positively impacted by this pioneering test, such as the story Helmy highlighted at the beginning of our call.

Now turning to Slide 14 to take a closer look at screening highlights for the third quarter of 2025. Starting with CRC screening, given the strong performance and growing demand, we have accelerated the building out of our commercial infrastructure beyond our original plan. In addition, the breakthrough nature of the Shield brand has provided us with strategic partnership opportunities, including our recently announced collaborations with Quest Diagnostics and PathGroup.

Shield continues to generate strong demand from both patients and physicians with high adherence rates. As exemplified by the patient story we shared earlier, we are seeing Shield tests get completed with blood samples received for more than 90% of ordered cases. This demonstrate the simplicity of Shield as a routine blood test for CRC screening that can be implemented into routine PCP practice. We are encouraged by the performance of our Shield CRC V2, which demonstrated solid clinical performance with improved sensitivity for stage I colorectal cancer.

Turning to our multi-cancer initiatives. We are very excited to announce that Shield Multi-Cancer is now available nationwide through our clinical data collection initiative. At our Investor Day last month, we shared strong real-world performance data for Shield MCD from a study of 9,251 individuals. Specificity was 99%, consistent with earlier NCI findings and positive predictive value was 41%, meaning that when Shield MCD is positive, there was a 41% likelihood of cancer being present.

Lastly, we are proud to partner with the American Cancer Society and look forward to ensuring that everyone has access to convenient and timely cancer screening so we can detect cancer earlier and provide opportunities for better outcomes.

Taking a closer look at our recent strategic partnerships to scale our commercial infrastructure on Slide 15. First, we were very excited to announce a strategic collaboration with Quest to expand and accelerate Shield access more broadly in the U.S. Quest's provider clients will be able to order Shield tests and receive the results directly through the Quest connectivity system.

We believe this strategic collaboration is valuable in two ways. First, it enables a better ordering experience and brings forward our nationwide EMR strategy by several years. This will gives us immediate connectivity to 650,000 clinician and hospital accounts in the Quest system. We believe this accelerated connectivity will drive our scale. We will also have access to deep logistical infrastructure, including 2,000 patient service centers, and 6,000 in-office phlebotomists in the United States. Second, Quest's promotional activities using their nationwide field force in combination with our own multi-hundred person sales force will further strengthen our competitive position in the primary care market. Quest's national commercial sales team will proactively educate primary care physicians and OB-GYNs about the Shield test, accelerating awareness and adoption among their ordering providers. We expect Shield to be available for physician order through Quest in the first quarter of 2026. We will continue to process all Shield test and control client services and billing and reimbursement operations.

In addition, we recently announced our partnership with PathGroup, which expands Shield's reach to more than 250 health system across 25 states representing another exciting accelerator for physician and patient access. We are looking forward to seeing the positive impact of our growing commercial infrastructure in 2026 and years to come. We also remain confident in the potential inclusion of Shield in the American Cancer Society guidelines in near future which should be a catalyst for broader patient access.

Moving on to Slide 16. Our goal has always been to detect many cancer types early when they are most treatable. With that in mind, we developed Shield as a multi-cancer detection platform.

Turning to Slide 17. And as I mentioned earlier, we have now broadened access to Shield multi-cancer detection. In order for a patient to access this result report, their physician will need to opt in to receive the multi-cancer report and the patient will need to authorize the release of medical records to Guardant Health. We successfully piloted this workflow in several accounts and following overwhelming positive feedback from physicians and strong participation by patients, we expanded this offering nationwide.

Moving on to Slide 18. The launch of this initiative establishes a scalable platform for clinical data generation, enables assessment of the utilization of MCD results in patient care and provides a new avenue to expand patient access to multi-cancer detection, bringing this important innovation to a broader population. This nationwide initiative is expected to reach hundreds of thousands of participants, making it one of the largest prospective evidence generation initiatives for early cancer detection.

Turning now to Slide 19. With the expansion of Shield to include MCD results together with patient authorization to release medical data, we are now well positioned to further strengthen our data moat. This high-quality data serves as a regulatory grade source of truth, providing details on each patient's cancer journey that were previously not accessible. We will generate large-scale prospective evidence about the performance, clinical value and safety profile. We believe this high-resolution data will power continuous improvement of Shield MCD and also lay the foundation to potentially expand into multi-disease detection.

With that, I will now turn the call over to Mike for more detail on our financials.

Thanks, AmirAli.

Turning to Slide 20. I will now review select financial highlights for the quarter ended September 30, 2025. Unless otherwise noted, all growth rates are year-over-year. Total revenue for the third quarter grew 39% to $265.2 million driven by strong performance across all 3 major revenue lines: oncology, biopharma and data, and screening. Oncology revenue increased 31% to $184.4 million primarily driven by another quarter of accelerated test volume growth. We reported approximately 74,000 oncology tests in the third quarter, representing 40% growth reflecting continued positive momentum across the portfolio.

Guardant360 Liquid delivered its fifth consecutive quarter of accelerating growth, with volumes up more than 30%, supported by the expanding clinical utility enabled by Smart apps launched over the past year. Guardant360 Tissue also had an exceptional quarter, showing strong year-over-year acceleration following the major product upgrade released in the second quarter. Reveal remains our fastest-growing oncology product, benefiting from CRC surveillance reimbursement achieved earlier this year and continued strength across both breast and lung cancer indications. As a reminder, we do not include Guardant Hereditary Cancer testing or IHC volumes in our reported totals. We continue to expect minimal revenue contribution from these new offerings through 2025.

Average selling prices remained stable compared to the prior quarter. Guardant360 Liquid was in the range of $3,000 to $3,100, Guardant360 Tissue was approximately $2,000, and Reveal was in the range of $600 to $700. We also recognized approximately $5 million of out-of-period oncology revenue in the third quarter compared to $12 million in the prior year period. Our biopharma and data business continued to perform well, with revenue increasing 18% to $54.7 million, which includes milestone revenue from 2 companion diagnostic approvals achieved during the quarter. The biopharma pipeline remains solid, providing confidence in both the near-term and long-term growth prospects. Screening revenue from Shield totaled $24.1 million generated from 24,000 tests reported during the quarter. Shield ASP was approximately $880 above expectations, reflecting our continued focus on Medicare-covered patients.

We also recognized approximately $3 million of out-of-period screening revenue, driven by better-than-expected reimbursement from Medicare Advantage payers for tests performed in the first half of 2025. This positive trend reinforces our confidence in both near-term and long-term expectations for Medicare Advantage reimbursement rates and overall Shield ASP targets.

Turning to Slide 21. We’re very pleased with the year-over-year improvement in non-GAAP gross margin, which increased to 66% in Q3 2025 compared to 63% in the prior year period. This improvement was primarily driven by a significant reduction in Reveal COGS, which have declined from over $1,000 per test in Q3 2024 to less than $500 per test, as well as strong progress in Shield gross margin.

Shield's non-GAAP gross margin improved from negative levels at the launch just over a year ago to 55% in the third quarter of 2025. This improvement reflects strong ASPs under the Medicare ADLT rate of $1,495, disciplined focus on reimbursable tests, and continued COGS reduction. Shield's non-GAAP cost per test again trended lower sequentially and continues to be below $500 per test, consistent with our operational plan. These gains reflect the ongoing benefits of increased Shield volume and disciplined cost management.

Turning to Slide 22. Non-GAAP operating expenses were $228.8 million in the third quarter, an increase of 22% in line with expectations. The increase was primarily driven by continued investments to expand our screening commercial infrastructure and scale sales and marketing for Shield. As we conclude 2025 and enter 2026, we will maintain focus on these investments to maximize our first-mover advantage in blood-based colorectal cancer screening.

Adjusted EBITDA loss was $45.5 million, an improvement of $10.7 million compared to a loss of $56.2 million in the third quarter of 2024. We remain disciplined in our approach to cash management. Free cash flow burn was $45.8 million, improving by $9.5 million compared to the prior year period. Importantly, excluding the screening business, Guardant generated positive free cash flow during the quarter, a significant milestone achieved one quarter ahead of our stated target. We expect the core business to remain free cash flow positive in the fourth quarter as well as for the full year 2026 and beyond. We ended the quarter with approximately $690 million in cash, cash equivalents, and restricted cash.

Turning to the full-year 2025 outlook on Slide 23. Based on our strong year-to-date performance, we are raising full-year 2025 revenue guidance for the third time this year to a range of $965 million to $970 million, representing approximately 31% growth compared to 2024. At the midpoint, this represents an increase of $47.5 million versus our prior range.

We now expect oncology revenue to grow approximately 25% year over year, up from prior guidance of 20%, driven by stronger-than-expected oncology volumes in the third quarter and higher expected volumes for the remainder of the year. We now forecast total oncology test volume to grow more than 30% compared to our previous expectation of greater than 27%. Our biopharma and data business remains on track to deliver mid-teens growth for the full year. We’re also increasing our Shield revenue guidance to $71 million to $73 million, up from $55 million to $60 million, reflecting higher expected volume of 80,000 to 82,000 tests compared to prior guidance of 68,000 to 73,000 tests.

With continued improvement in gross margins, we’re raising our full-year non-GAAP gross margin guidance to 64% to 65%, up from 63% to 64%. As previously outlined, we plan to reinvest incremental screening gross profit to accelerate commercial expansion. Accordingly, we now expect 2025 non-GAAP operating expenses to be in the range of $865 million to $875 million, representing a 14% to 16% increase compared to 2024.

Finally, consistent with our long-term financial roadmap, we remain committed to reducing cash burn each year and achieving company-wide cash flow breakeven by the end of 2027. For the full year 2025, we continue to expect free cash flow burn of $225 million to $235 million, an improvement from $275 million in 2024.

Turning to Slide 24. We began 2025 with an ambitious set of strategic and operational objectives. Through our strong execution, we’ve delivered on nearly all of them, and we expect continued momentum as we close out the year. Our progress this quarter positions Guardant for sustained success in 2026 with continued oncology volume growth and strong Shield adoption.

With that, we will now open the call for questions.

Thank you. [Operator Instructions] The first question comes from the line of Bradley Bowers with Mizuho.

A strong performance across the businesses, but I am going to focus on Shield here. I was wondering if you could walk us through the Shield ASP dynamics exiting the year. Continued strong pricing, I don't think it's surprising given the ADLT pricing, but that $900 we’re exiting the year at. It’s supposed to walk down to $700 by 2028. I know there are some mix implications there, but is it a steady degradation? Is there a fallout expected as ADLT pricing rolls off the initial phase at the end of this year? Any color on the phasing of that would be helpful. Thank you.

Yes, Brad. This is Mike. I can take that. Yes, I mean, to break down the -- what's in the Shield ASP, we have the Medicare rates at $1,495 that came into play at the start of the second quarter. We’re also receiving really good payment from Medicare Advantage payers. And so, when they are paying us, they are paying us at this $1,495 rate also. And at the moment, the majority of our volume is skewed towards Medicare and Medicare Advantage. And then we have a tranche of commercial patients, and we’re effectively getting paid more or less 0 for those.

And so, as we look at over the next few years, we’re very confident in the $1,495 rate -- ADLT rate going forward. And in fact, we’ve just submitted our package back to Medicare on the date of submission of the pricing over the last six months, and that should help us maintain this $1,495 rate now, at least for the next 2 years. And going forward, also, we expect Medicare Advantage to continue to be strong. In fact, we would hope that it can get stronger than where it’s today.

The fluctuation over the next couple of years is going to be the percentage of commercial payer patients that we have and how quickly we can ramp up the commercial reimbursement there. And so, we’re assuming in 2028, there’s just a higher proportion of commercial patients in the mix. And it’s going to take us time to establish that reimbursement rate. But overall, we’re really happy with where the ASP is today, and we think it bodes well for as we go into 2026 and beyond.

The next question is from the line of Doug Schenkel with Wolfe Research.

So another question on Shield. You mentioned at the Investor Day, and as well as in your prepared remarks that potential ACS guideline inclusion later this year could set the stage for commercial coverage and I think, at least 10 states. And we believe Anthem and other large Blues are watching closely. So to the best of our knowledge, ACS concluded their CRC screening guidelines review earlier this month. With that in mind, is guideline inclusion at this point a real possibility by year-end with ACS?

And then once guidelines are in place, how long do you think it’s going to take for that to translate into you actually getting paid? And then the final component of the question is, beyond those initial 10 or so states, there are other states like Florida and Louisiana where mandates have been brought in to include ACS as well as NCCN in addition to USPSTF. So if we think about that broader universe of states, which I think maybe gets you closer to 17, is it likely that reimbursement could occur not just in the initial 10%, but closer to 20% over the next year or so?

Thank you, Doug, for your question. Yes, based on what we know, it appears that ACS research team is almost done with their work. So we remain confident about this potential for Shield to be included in near future. We are monitoring the situation very closely, but we are very optimistic about that. In terms of the guide, like, it’s not part of this year guide. We are not counting on any kind of upside associated with the ACS guideline and, it’s going to take some time. When we go into the guideline, it gives us initially some upper hand, and it should have a strong -- it should have a positive impact on our appeal success rate initially. And then at some point, that would result into product coverage and contracting successes.

I am proud of what our team has achieved so far on trying to broaden access to Shield. You noted Florida now through a consortium of supporters of making sure that innovative technology becomes accessible. Now, for instance, Medicaid patient population in Florida have access to tests like Shield, and we are very proud of that. And in general, we are very pleased with some of the positive and regular dialogue that even we have with the administration about their priorities around cancer screening, around prevention, around making America healthy. And I am excited that looks like both the President and Secretary are looking for ways to see how maybe the rate of cancer can get reduced in the country and how could we try to bring innovations to patients in a faster way. But we'll see what happens. But, obviously, we are not counting on any of those successes in our drive at this time.

The next question comes from the line of Puneet Souda with Leerink Partners.

Really impressive quarter here and really strong guide. If I may, AmirAli, first one on Shield. Just growth is accelerating on volumes, rightfully so, new product and ASP is also up. How should we think about 2026 growth for Shield and any early reception details that you can talk about on the MCD side? What's the early attach rate? And for Helmy, it's been almost a decade since you launched G360 when it appeared on the market for the first time. It' really impressive to see 10 years later, this product is growing 30% plus. Maybe just talk to us about what's behind that and how should we think about the growth going forward here for the Liquid G360, which has been impressive?

Maybe I will make the Shield part quick so Helmy can talk to you about the oncology side. So as you have seen, we consistently raised our outlook throughout this year. We are very pleased with what we are seeing, the momentum that we are seeing. We want to be thoughtful and not get ahead of our skis. So, I think still it's too early for us to comment about 2026. At the right time, we will talk about it, but we continue to be very confident about the long-term outlooks that we shared in our Investor Day.

Yes. No, we're very pleased with the performance. It's actually been 11 years and counting in from when we launched in 360 and so, to see it grow at this rate, I think at this point in the product cycle it's really pleasing, but I think it’s what we expected in the sense that many people think of this as a test and they pattern match it to other tests in the market. But it truly is an application platform. When you think about these Smart apps that we’re introducing and really the multiplication of clinical utility and ability and capabilities of this platform, this is just the beginning in terms of where liquid biopsy can go. I mean, that’s the point of liquid biopsy is you can come in, you can test many more patients, you can increase access. But you can test them longitudinally as well. And we’re still at the very, very early innings in terms of where this can go, where this technology can go just in oncology. So I think you are going to see a lot more, I think, of this trajectory in the coming years as we continue to expand on the capabilities of Guardant360 over the next decade.

The next question comes from the line of Subbu Nambi with Guggenheim.

If you were to put a timeline -- if we were to put a timeline to NCD FDA approval based on Shield trajectory next year, would FDA submission for MCD in late 2027 be a reasonable expectation?

For MCD, we just actually broadened access, and we just actually started getting access to this clinical data that I talked about during our Investor Day and the prepared remarks. So we need to monitor it and see how quickly we can build that evidence. But we are very optimistic that potentially through the way that we are doing, we can get access to hundreds of thousands of patient data and monitor actually the impact of MCD testing in the clinical value, performance, safety. It’s still too early for us to specifically put a timeline for FDA approval. But we would monitor the situation closely and as we get more confidence, maybe we can talk about it at the right time.

The next question comes from the line of Patrick Donnelly with Citi.

Helmy, maybe one for you on Reveal. I know in the past, you've talked about driving the test per patient higher. Can you just talk about the traction there given the bigger push internally? What kind of progress you're seeing? Where can that go over the relative near term? And I know during the prepared remarks you talked about obviously the ongoing studies, the additional tumor types. Can you just talk about what we should be looking for and the key catalysts on the Reveal side here over the next couple of quarters to keep an eye on?

Yes. Great question. I think we said at the beginning of the year, as we got the surveillance indication from a reimbursement point of view for Reveal that would be turning on a lot of the capabilities to be able to pull in subsequent test orders and so on. And I am pleased to report that, we’ve put a lot of those in place, and we’re seeing some of the benefits of that and the return on investment there.

So we know we can pull in subsequent orders now in a very straightforward way and so that’s going to pay dividends across our blood-based portfolio as we think about the emergence and really, the place where longitudinal testing will sit in terms of management of patients in oncology with things like SERENA-6 in terms of ESR1 with the upcoming launch of our therapy monitoring based on Reveal. And then, obviously, with Reveal itself in the MRD setting, recurrence monitoring setting. So yes, really great progress. The number of tests per patient has gone up pretty nicely, and we’re still, I would say, very much in the early cycles of really capitalizing on that investment.

The next question comes from the line of Tycho Peterson with Jefferies.

I would love to hear your views on the PEGASUS data and just how you think about that having any impact on just MRD-driven therapy management? And then how are you thinking about clinical utility evidence in general and NCCN guidelines?

Yes, PEGASUS was a really interesting study. It was a Phase II signal finding study, and I think there are a few things that showed that I think were exciting to me, which is the fact that you could spare something like 75% of patients from chemotherapy, which meant, huge, huge reduction in terms of neurotoxicity and other toxicities related to such really harsh chemotherapy. And so I think PEGASUS was based on our previous version of Reveal. And so I think we’re really looking forward to TRACC, which is based on a newer version.

And really, the field, having larger datasets to really understand exactly where the threshold should be in terms of escalation and de-escalation in terms of patients. But I think it’s clear that I think there can be a lot of benefit by using this additional data in terms of ctDNA in the adjuvant and surveillance settings. But I think this is a good foundation and one that we can build on as we continue investing in both clinical validity and clinical utility studies around our Reveal platform.

The next question comes from the line of Bill Bonello with Craig Hallum.

I just want to push a little deeper on [Suneet's] third question about the growth in Guardant360. Could you just give us some sense today? I mean, if we think about what’s out there that’s driving, there’s the underlying growth, there’s the fact that you are probably taking share. But I am also curious about where we stand today in terms of a paradigm shift to liquid first or perhaps to combination testing with liquid and solid tumor. And then to what extent were – we are seeing some of the repeat testing that you are talking about or the use of 360 for monitoring? Just trying to get a sense of what inning we’re at in terms of some of these new growth drivers and how much of that is still in front of us?

Yes. Great, great question. So we’re still very early even in the penetration of liquid biopsy in terms of one test per lifetime. And so given, the capabilities of 360 right now, they are just mind-blowing to a lot of physicians just in terms of the depth, the sensitivity, the application space. We see that growth -- in just that initial setting. So that means not only market growth, but we’re seeing from what we can see, significant share gains as well as a result. Then there are other growth drivers we’re seeing. The fact that concurrent testing will likely become the standard of care of both tissue and liquid. And so that is also another growth driver and we're starting to see that really, really take off.

And then finally, the test for patients. And so we estimate at maturation that we should be able to go from 1 test per patient per lifetime to something like 4.5 or 4 or 5 tests per patient per year which, obviously means more than, probably doubling of where the market is today – sorry more than a 10x in terms of where the market is today.

And so that’s really exciting in terms of where things are going, and this is things like SERENA-6 in terms of ESR1, longitudinal monitoring, therapy monitoring, the data that we have with IO monitoring, with chemo monitoring, and so on. All of that will feed into essentially establishing this new paradigm of essentially monitoring patients with ctDNA. We’re already seeing our biopharma partners use this type of testing to -- in their Phase I, Phase II, Phase III studies using it to decide do they scale Phase I to Phase II, using it for dosing. And so that’s the other piece that I think is not very well appreciated is that a lot of tests you launch them they are used exactly the same way 10 years later or 15 years later and so on. They only have one function.

The application space and utility of how you use the -- something like Guardant360 and Guardant Reveal is really multiplying quarter by quarter and year by year. And so, yes, this is a true platform. That word is often overused, but this is a true platform, and you are seeing what that means in terms of our volume growth and the trajectory that we laid out at our Investor Day.

The next question comes from the line of Michael Ryskin with Bank of America.

This is Aaron on for Mike. I wanted to dive into Reveal volumes and specifically Reveal versus Ultra and how you guys are thinking about the R&D investment needed in both of those assets? And then the second part of that is MRD is still a fairly open space,10% penetrated, what people are saying. So I guess, how are you guys looking at the market? How are you guys looking at growth? And how should we be expecting both of those assets to grow over the next 3 years?

Yes. We’re very excited about our MRD franchise. Reveal is the leading tissue-free MRD test in the market. We know that there will be essentially 2 parts of the market that will be important, the tissue-free side and the tumor-informed side of things. And we're very pleased in terms of where we sit in the tissue-free side. It’s our fastest-growing product in oncology. And the amount of data, the amount of investments, we have a 10x data generation planned as we presented before next year. And so that flywheel is really chugging away. And so we’re excited about that trajectory.

And then in terms of the tumor-informed side I think we agree with you, there’s a lot of opportunity there in terms of a test that can really hit the needs of both biopharma and clinicians in terms of sensitivity that is really acquired for that setting. And, yes, we’re just very pleased with the technology that we’ve developed. If you think about it, just everything we’ve built as a company is at a really nice point. The fact that we’ve really chugging away on our tissue volumes and the capabilities we have with using very low amounts of input material, very fast turnaround times. The sensitivity we have on the liquid biopsy side and the capabilities, COGS down and the speed to results, all of that is coming together in Reveal Ultra. And I think it’s going to be a product that will, frankly, blow everyone away once we launch it. Very excited for that and making really good progress.

The next question comes from the line of Daniel Markowitz with Evercore ISI. Daniel, your line may be muted. Our next question comes from the line of Mark Massaro with BTIG.

The first one is for you, AmirAli. Just looking at the Shield, it’s great to see this trajectory. Is it reasonable to think in the near term that 1,000 sequential increase from the prior quarter is the right way to think about this just looking at the Q4 implied guide at the high end, it’s plus 9%. You just did plus 8% prior quarter plus 7%. Or -- so I guess I am asking if this is a reasonable run rate in the near term? Or do you think there’s obviously upside from partnerships with Quest, PathGroup, certainly guideline inclusion and potential DTC uplift? So that’s my first part.

The second part is for Helmy. Helmy, can you just give us a sense for Reveal Ultra? I believe this is the tumor-informed that can go down to 1 part per million. Just give us a sense for -- maybe if you could clarify if that is commercially launched now and how we should think about the timing of CMS reimbursement and additional data readouts? Thanks.

Thanks, Mark. So in terms of sequential growth, like our guide, what has ended in the midpoint is like another 8,000 Q-over-Q growth in Q4. We are going to monitor the situation closely. And again, we don’t want to get ahead of our skis and see what’s going to happen and for next year, we are going to talk about it at the right time. There are a bunch of catalysts still in front of us. There’s Quest, PathGroup collaboration should be a positive thing. Guideline inclusion is definitely a positive thing. Continuous build-out of our own commercial team as we go into next year would be a positive thing. So -- and we are confident about the target that we put out there for 2028. So -- but we go at it one step at a time, and we are very excited to see what’s going to happen in Q4.

Yes. In terms of Reveal Ultra, I think the nice thing is we built such strong capabilities around MRD. When you think about the R&D and all the clinical studies, tens of thousands of samples and many of those we’ve actually retained tissue. So it’s actually, not, very heavy investment for us to essentially leverage that to really come out with the Ultra technology, the tumor-informed technology we have. We’re seeing really good data, really excited in terms of where this can go.

In terms of the sensitivity, we think it can bring it down to a much lower level than exists in the field or frankly, exists in the pipeline of companies we’ve seen out there. And I would say that in terms of timing, we’re keeping that close to the chest. So stay tuned, but making good progress and we wouldn’t be talking about it if it wasn’t something that was not in the too distant future.

The next question comes from the line of Casey Woodring with JPMorgan.

On the Shield performance in the quarter, maybe as a follow-up to Mark's question. Can you provide any KPIs around maybe average testing frequency per physician and whether volumes are coming from new time CRC screeners?

And then just my second question here. Mike, if you can provide any color on gross margin for Shield and Reveal embedded in the updated guide of 64% to 65% for this year, that would be helpful?

Yes. Maybe some KPIs. Actually, it's exciting that the breadth of ordering continues to increase Q-over-Q. The depth of ordering continues to be very strong. So once the accounts actually start using Shield and we go through activation, the depth of ordering is very solid, which is really an endorsement of how deep this market is and mainly how many under screened cancer patients are out there in the accounts that we are going to. So we are seeing their doctors. We are successfully leading them and so forth. So the other KPI to share, which we are very excited about is we continue to see very high adherence rate when the doctors order their stuffs more than [indiscernible] gets converted to a sample received in our lab, which really gives us bunch of efficiencies in our S&M investments.

And Don on the gross margins which yield -- in the prepared remarks we mentioned that the Shield gross margin this quarter, Q3 was 55%. And so, ISPs are close to $900 and our cost per test now is consistently lower than $500. So we made really great progress with Shield’s gross margin. And then on the Reveal side, again we’ve made fantastic progress over the last 9 months or so. And just to bring that out a bit know how ISPs for Reveal continue to be in the $600 to $700 range. And again, since this part of the year Reveal cost per test are consistently below $500. So, we have a nice gross margin on Reveal. It’s a little bit lower than the 55% we’ve got on Shield. But there really what’s helping drive our overall cleanly gross margin and we see in that the positive impact in that we’re going from 63% in Q3 last year to 66%. So I think good progress across the board with gross margin.

The next question comes from the line of Kyle Mikson with Canaccord.

Congrats on the quarter. On Reveal, is it still possible you get ADLT status and breast Medicare coverage by the end of this year? Is that more likely a '26 milestone? And then secondly, AmirAli, we had a competitor this week announced advanced adenoma sensitivity data for its colon cancer blood tests. The confidence interval lower bound was 15% and the study had a lot of very small lesions. Just curious if you think that a test with AA materially higher than the 13% for Shield would pose a threat and you would like, when they aim to improve upon your AA data still?

Yes. I mean ADLT status is still a work in progress, obviously, with the government shutdown paused some of the discussions a little bit. And then we're still working in breast and IO. We've always said probably more likely early next year. And yes, we're still, I think, on track for that.

Regarding the data disclosures, we -- obviously, we applaud anybody who's trying to contribute in this difficult area. This is a hard science area. And we feel very comfortable with our leadership position. And our technology stack, our data, and what we are doing.

We have seen similar results in this field now a few times. Again, this is a hard field. It is a hard science field. And we believe we have the best tech stack, very innovative technology at home brew that gives us confidence. We have a 3 year head start on CRC now. And know, probably even much longer on the multi-cancer side relative to some of these competitions. So we feel very good with our position at this time. And, definitely, there are some fine activities that we are working on. We will see what happens.

The next question is from the line of Luke Sergott with Barclays.

Just wanted to touch here on the step-up in OpEx that you guys have for the year and implied in 4Q. And really just dig in where that spend -- the incremental spend is going and where you guys think from an S&M perspective? Where you guys want to exit the year as a number of reps as you think about Shield and oncology and Reveal? And how that -- if you're able to pull forward any of those costs given the success you've had in some of these -- some of the other launches?

Yes. I mean for the OpEx step-up, it's pretty much all in the sales and marketing line. I think we've been consistent throughout the year, whereby we said we're going to be reinvesting any incremental gross profit in screening back into the sales and marketing line to really drive that commercial build-out. So -- and we'll continue to do that. I think it's the biggest focus for us as we look to scale.

We said on the screening side, we've now got over 250 salespeople out in the field. So that's a significant ramp-up during the year, and we'll continue to look at how we build that out. On the oncology side, it's a little bit larger than that. And we've got a very sort of well-built out commercial infrastructure with oncology. But yes, as we look forward and go into 2026, I think you should expect to see a similar ramp in the sales and marketing line. We're very focused in the R&D line and the G&A line and keeping them relatively flat. And so I think that's the plan for the next 12 months.

The next question comes from the line of Daniel Brennan with TD Cowen.

Congrats on the quarter. Maybe just on G360, just a couple. Maybe one for Mike and then one for Helmy. Just on the guide, I know that clinical oncology volume guide is now greater than 30. Does that contemplate like a big step down from the G360 line, which is accelerated tremendously year to date, obviously from the Q3 30%? And then B, more so for Helmy. I know you have given a lot of color on the excitement over the outlook for G360. But could you give a little more color on the acceleration you have seen year to date? Is it more share gains which you talked about?

Like are you seeing like hospitals consolidate? Do you think it is more just penetration of CGP? Or do you think it is more like this test per patient pickup? Any way you can kind of dissect a little bit of this really strong acceleration?

Yes. Maybe I will just start on Q4 guide. So, we had a great Q3. I think our guide for Guardant360 volume and for overall oncology volume, it implies sequential growth in Q4. It implies a very strong year-over-year growth in volume. So yes, if you back into it, it’s over 30% year-over-year growth in Q4. So I think we have just continued to expect the momentum that we saw in Q3 continue to Q4. So I think for us, things are looking very strong as we get towards the end of the year.

Yes. In terms of growth driver, I think what you are seeing really is the fact that it is just a very compelling test from a value proposition. So I think a lot of what you are seeing is some of the share gains from the other tests in the market from other hospitals and so on. So that’s been exciting. We are seeing a little bit of the increase in testing in terms of longitudinally, but I would say that’s a very minor part. I think that’s still a lot of -- that’s still another major growth catalyst for us in the future that we have not really tapped into.

And then the third piece is this test has so many capabilities. Things like being able to determine the type of cancer, what someone who has a cancer of unknown primary, subtyping. So if you think about the long tail of cancers where liquid biopsies and even tissue -- tumor biopsies aren’t really utilized, the fact that we have this smart platform with epigenetics and so on that can give so much more insight into tumor biology. I think you are seeing penetration into some of these longer tail of cancers as well.

Our last question comes from the line of Dan Arias with Stifel.

Helmy, I just wanted to go back to Reveal. Can you maybe talk about where things are on the commercial side when it comes to reimbursement in colorectal? What’s a good ballpark number at this point for just the percentage of tests that are getting paid for, I guess, Stage II and Stage III patients would be the right subpopulation to ask about there? But really just trying to understand [indiscernible] side of CMS in your key indication there?

Yes Dan, it’s Mike here. It cut out a bit towards the end, but I think you're asking about Reveal reimbursements with CRC. CRC now is -- it's roughly 50% of our volume. It continues to be at that sort of level and the rest being made up at the moment from breast and lung and where we are getting reimbursed is for all of the -- now whenever we run a CRC test, we're getting reimbursed for all of these tests that we do for Medicare, and that's at the $1,640 rate. And we're getting good pull-through with Medicare Advantage. We're starting to see traction with commercial payers. That's improving all of the time. And so I think we're feeling good at where the reimbursement level is.

And then as we look forward, we think there's continuous runway with Reveal. Again, more and more Medicare Advantage and commercial payments on the CRC side. But as we just mentioned, we are anticipating Reveal breast reimbursement. We've submitted the data package to MolDX for Reveal IO. And so hopefully, going forward, we're getting incremental Medicare reimbursement and incremental reimbursement from all of the payers as we move into '26.

That was our last question. That concludes today's call. Thank you for your participation and enjoy the rest of your day.

Good morning, everybody, and thank you for joining us for the Guardant Health 2025 Investor Day. I'm Zarak Khurshid, Vice President of Investor Relations. It's been almost 7 years since our IPO and 2 years since our last Investor Day. Given where we are today and the progress we've made in the last 2 years, we're incredibly excited to provide an update on the business and share more details about where Guardant is headed. We've got an exciting day planned for you guys. Hopefully, we can advance the slides. And we're going to be making some forward-looking statements.

We have our safe harbor agreement here. We'll also be reviewing some of the non-GAAP measures throughout today's presentation. A reconciliation of those measures back to GAAP can be found in the SEC filings. Additionally, we'll be providing -- we won't be providing any color on Q3 or updating our outlook for the year. We will provide Q3 results and an updated outlook on our earnings call. And as I said, we have a really action-packed day here plan for you guys. The CEOs are going to make some introductory remarks, and then we're going to dive into the innovation engine and Smart platform with Darya. After that, Craig will do a deep dive into our learning engine. The team will then provide a refresh on our integrated portfolio of products with updates on therapy selection, MRD, Biopharma and Chris Freeman will do a deep dive into our oncology commercial organization. Then Mike will walk us through that financial road map for the next few years, and we'll close it out with the founders again and jump into about 45 minutes of Q&A.

With that, I'd like to introduce Helmy Eltoukhy and AmirAli Talasaz, co-CEOs and founders of Guardant Health.

Well, it's really exciting to see so many familiar faces and to present really the exciting developments we have in our pipeline as well as some of the new targets that we have for the business. So Guardant, we are on a mission to guard wellness and give every person more time free, not just from cancer, but for most diseases, 13 years ago when we started Guardant, the idea that a simple blood draw could replace invasive biopsies or detect cancer early seem frankly impossible to many. People thought it was naive to imagine that one day of blood test could it guide treatment in advanced cancer or that same platform could enable early detection during a routine visit to a primary care doctor.

Fast forward to today, some of those same ideas are no longer viewed as science fiction. They are now recognized as some of the most important and largest markets in all of health care. The broader industry competitors included, have validated that vision. And for us, that's the ultimate compliment.

Over the past decade, we've not only advanced the science, but more importantly, we've turned a vision into execution. We've built a world-class commercial team delivered category-defining products and established Guardant as a leader in liquid biopsy. And yet I would argue that we are still just getting started. At Guardant, everything begins and ends with one value, putting patients first. This guiding principle drives the 3 pillars that make us different. The first, innovation, by blazing a trail with exponential thinking, we pursue bold unconventional solutions that directly improve patient care. Two, execution through commercial and operational excellence fueled by resilience and grit, we deliver groundbreaking innovations rapidly at scale, so more patients benefit faster.

And then finally, data by turning insights and intelligence into advancements, we leverage a powerful data treasury to accelerate progress and personalize treatment for every patient. Together, these pillars reinforce our commitment to putting patients first and transforming the future of cancer care.

And since the founding days of Guardant Health, back in 2012, 10 years past, more than 10 years, we made substantial progress delivering on the promise that we made to the patients, to offer solutions across the continuum of care. As of today, we are the only company in the cancer liquid biopsy field that has offerings spanning from late-stage cancer management, both on the liquid and tissue front, MRD and early cancer detection with Shield. We have touched nearly 1 million patients ordered by over 12,000 oncologists and thousands of primary care physicians.

2 years ago at our last Investor Day, we provided a deep dive into our Smart platform. And we talked about how it would change the whole field and how it would be the foundational technology driving the next paradigm shift in the liquid biopsy detection. We imagine the days that these new molecule insights powered by a Smart platform would unleash opportunities and powerful waves of new applications and clinical value. And that is exactly what have played out commercially in a very meaningful way just 2 years later.

Our Smart platform now underpins and its the backbone of all of our products across continuum of care. And it's effectively now the cornerstone of the robust pipeline and the growth driver for our business. Here is the list of all of the product and product upgrades just during the last few handful years. We are proud of the accelerated introduction of new products and product upgrades since last 2 years that we met in our last Investor Day. And this progress, accelerated progress is only the testament of the quality of the team that we have and their dedication, but also to the tech stack and the learning engine that we have built over all these years.

And today, we are very excited to announce that we are expanding the Shield product offering to include multi-cancer detection results. This will be available nationally next month in the month of October. We are very excited about the days ahead of us. And throughout the day, you're going to hear more about our strategy for this multi-cancer offering.

As of second quarter of 2025, we are roughly 2,300 people strong. Our team of scientists and engineers with over 295 MD PhDs are truly world class. We are very proud of that. Our commercial team is top ranked in terms of share of voice with oncologists, and you will hear more details about it from Chris today. On the right side, you see the results from an industry survey showing that 81% of employees rated Guardant as a great place to work. By the way, we'll have you know that this 81% is not census adjustment. It's a real number.

Now let me share a little bit about our commitment to execution. To recap, for 2025, the midpoint of our guidance, we expect revenue of approximately $920 million. That's 24% growth this year on top of a very strong base. Importantly, growth has not only been sustained but has accelerated. Since our last Investor Day, our 2-year compound annual growth rate has increased to 28%, underscoring the strength of execution across the entire portfolio. This acceleration reflects disciplined operational performance, continued adoption in advanced cancer and MRD, expansion into new indications and progress in early detection. Together, these drivers have created durable momentum.

Mike will walk you through the financial details, but the takeaway here is clear. We set ambitious goals, and we have met or exceeded them through focused execution. More specifically, this next slide highlights what we've accomplished since our last Investor Day. Over the past 2 years, we have delivered nearly everything we set out to achieve. In many cases, we've gone further. On the oncology side, we made significant progress in therapy selection, migrating both our liquid and tissue tests to our Smart platform, achieved increased reimbursement for Guardant360 and launched 15 apps on Guardant360 liquid that has greatly accelerated growth.

In MRD, we've delivered an important milestone securing CMS reimbursement for colorectal cancer in the surveillance setting, reducing COGS by 50% and submitting breast and I/O indications to MolDX for Medicare reimbursement. And in screening, we've established an entirely new category with Shield, we're on track for Shield to be one of the most successful diagnostic launches in history outside of COVID testing. This has been fueled by Shield's FDA approval with a primary label NCCN guideline inclusion and differentiated Medicare pricing. Taken together, this represents not only achievements against our plan, but exceeding our own lofty expectations and key milestones. It demonstrates our ability to innovate, execute and scale simultaneously while continuing to advance patient care.

From the beginning, Guardant has been a blood-first company. Our platform was predicated on the idea that continuous improvement on compound innovation and the key to this improvement is the learning from every sample that we sequence and every patient that we help. To this end, since launching commercially in advanced cancers in 2014, we've been building what is now, we believe, the largest blood-based biobank in the world. With the acceleration of oncology volumes and early traction of Shield in its first year, this biobank has grown to over 1 million patient samples, and it continues to expand rapidly.

This resource is more than just a number. It represents a unique and durable competitive moat. Each patient sample contributes to a data set that improves the sensitivity of our tests, accelerates product development and generates insight that no one else in the industry can replicate. And as Shield adoption continues to massively scale, this biobank will only become more valuable, strengthening both our scientific leadership and our ability to deliver for patients.

From the start, we knew that data would be the key to expanding beyond late-stage cancer into earlier points of the patient journey. Each step upstream in cancer requires exponentially more data to identify weaker signals and molecular signatures. A critical breakthrough came with the introduction of our Smart platform, the first of its kind AI-powered biochemistry platform for simultaneous high-performance genomic and epigenomic data generation. With Smart, every sample produces roughly to 10x to 100x more information than our earlier genomics-only assays. This has fundamentally changed the slope of our data curve.

You can see that inflection point clearly in 2023 when Smart was introduced into our clinical portfolio. Over the last 2 years, strong growth in Reveal, the launch of 15 smart apps on Guardant360 LVT and the rapid uptake of Shield have driven what can only be described as a data explosion. Today, our data Treasury is expanding at a rate of about 1 petabyte per week. We have now crossed over 200 petabytes and in the next couple of years will reach 1 exabyte of data. I think it's hard to understand the scale of the data we are generating as a company. To put that in perspective, Guardant now generates more than 20x the data Visa does from global transaction activity and Visa processes roughly 1 billion transactions per week. And we haven't stopped at genomics and epigenomics. We've layered in multimodal data sources, real-world evidence making our database even richer, more comprehensive and powerful for discovery and development of groundbreaking new applications.

And now through application of the AI tools. We are leveraging this data treasure that we built together, and this is helping us to bring powerful and pioneering new products for our patients to market faster than ever. This integrated learning engine that we put together provides us higher resolution understanding of the biology, our technology and help us to upgrade our current products and also build entirely new ones. For the clinical business, help us to find novel signatures for faster drug discovery which is relevant to our biopharma services and also help us to learn about some data around our commercial engine and also helps with the decision support tools for the physician.

Just as a reminder, all of our products across continuum of care, Reveal, Shield CRC, Shield MCD and the new apps that we have launched for 360, all of them actually have been built based on this data and the insight that we have and the power of the AI on top of that data. Now with the explosion of the data that you heard earlier, and the AI tools that we are using. We believe the rate of innovation at Guardant is just going to increase and increase. And effectively, all the product testament that we talked about earlier is a testament of this growth and acceleration of innovation and development.

What our team has achieved during the last one decade has been extraordinary. We've taken liquid biopsy from just a bold idea a decade ago to standard of care, which is reshaping the way patients are getting managed today. We are not just building for the future, we are growing rapidly as we speak. Guardant is the leader in therapy selection, in tissue free MRD and blood-based CRC cancer screening, 3 of the biggest opportunities that exists in health care industry. And even as just exciting is what's in front of us. The more powerful applications are just beginning to unfold. The most profound impact on patients are just about to come. Guardant is the leader in the liquid biopsy field today, and we are just getting started.

If you look across history, transformative technologies rarely move in a straight line. They advanced in successive S curves, each breakthrough enabling the next wave of applications. We've seen this with electricity, which we began by powering white bulbs, but quickly scaled the factories, transportation and ultimately, the digital age. We've seen it with semiconductors, where the first chips made basic computation possible, then unleased personal computing, the Internet, mobile and now artificial intelligence. Each curve larger and more impactful than the one before.

Guardant's journey has followed that same pattern. We've unlocked 3 S curves already. The first one therapy selection, opening up a $10 billion market; second, minimum residual disease, a $20 billion market; and the third, cancer screening $50 billion market. Each step expanded both the utility of our platform and the scale of the opportunity. And now as our technology grows in power and reach, it opens the door to the next S-curve, multi-disease screening. Shield is a foundation, but the vision is much broader. Routine blood testing that not only finds cancer, but helps intercept many of the most serious diseases at their earliest and most treatable stages. In that future, a simple blood draw could become one of the most important tools in preventative medicine, helping physicians protect health and not just treat disease. This is the arc we are building towards a succession of S curves, each unlocking more values for patients, for physicians and for society.

And this is some of the topics we are going to cover today. You will learn about our small platform more, which is fueling the best-of-breed innovation platform. This proprietary epigenomic tech stack that we built, combining it with multimodal data treasury, AI on top, which is fueling our growth. You're going to hear about the power of Infinity AI learning engine which is really unlocking opportunities across the organization for us. We are going to talk about oncology business acceleration. How these smart apps is fueling the new wave of growth for therapy selection.

We are going to cover MRD and the fact that we are the #1 player in the tissue free MRD. We talked about our industry-leading biopharma business and how it's strategically connected to everything that we do. We are going to talk about Shield as the winner in the blood-based screening field, Shield as a blockbuster products, strong first mover advantage, which is fairly increasing with what we are going to do in the field of multi-cancer detection expansion. And finally, Michael would update our financial outlook.

With that, I would like to welcome Darya, our Chief Technology Officer, to come to the stage and talk about our technology and innovation engine. Darya?

Good morning. Two years ago, we spoke about transformative potential of our technology to redefine liquid biopsy diagnostics. Today, I will show how that vision was actually transformed into reality. Smart platform now powers our products across the whole portfolio suite. And with that, we've generated the data that now transforms our assay-driven innovation into data-driven innovation with Infinity AI, powering the next wave of advancement.

Guardant has pioneered the field of liquid biopsy with genomics more than a decade ago, transforming precision oncology, yet the biology of cancer is too complex to be explained by mutations alone. We're now leading the multi-model revolution with epigenomics and genomics, revealing underlying biologic unprecedented resolution. We're changing how clinical decisions are made to detect cancer, monitor cancer and treat cancer.

Our Smart platform is uniquely designed to capture both the genomic hardware, the mutations define the structure of the tumor and epigenomic software that determines how that structure actually functions. Think about genomics as the hardware components that exist, but without epigenomics, you're looking at CPUs without knowing what software is running on them. The epigenomic layer reveals that functional information or tumor phenotype. It tells us how the tumor works, how it integrates with the immune system, how it evolves under evolution of -- with treatment and many, many more insights. That combined view of epigenomic and genomics, provide a more clear -- a more full picture of the system where both tumor genotype and tumor phenotype is revealed from a single analysis.

This Leap in Guardant's technology has opened multiple aspects of growth as you just heard from Helmy. With genomics opening up therapy selection, epigenomics allowed us to detect tumors and quantify tumors at very low tumor fractions in circulation, unlocking early-stage disease, MRD and screening. Powered by epigenomic data generated through that platform. We're now developing differentiating epigenomic capabilities that completely change what we can do in therapy selection. We have now reaccelerated that growth, and I'm excited about the commercial updates that you will hear from Chris that reflects on that.

This is not a onetime advance. It's a flywheel of innovation that positions us to move into multi-disease screening in the future. So how do we harvest the power of epigenomics with our Smart platform to have been assigned the class in epigenomics one more time. Imagine the genome-wide measurement system, where methylation can be profiled across thousands of epigenomic regions and the methylation intensity is measured for each one of them in every sample we test. Here, the signal is specific to colorectal cancer, light up in specific regions of the genome at intensity level that roughly corresponds to the tumor fraction. In lung cancer, in breast cancer, it signals line up in alternate regions of the genome, in this case, for example sample with lower tumor fraction.

What is important is, as we collect more data points, for more patients as we profile more regions of the genome. We're getting this map with higher and higher level of resolution where we can now not only map these diseases but also subtypes of diseases and more refined phenotypes of how that tumor works as shown here for triple-negative breast cancer as an example. Given the richness of biology encoded methylation, we can both detect and quantify tumors using the signal intensity, and characterize them and predict how they would respond to therapies based on the locations where the signals light up in the genome.

So how was this possible to deliver? The efficient extraction of this rich signal really comes from a decade of compound innovation, where proprietary and patent protected biochemistry allows us to deliver both genomic and epigenomic insights from a single pressure sample without loss of signal in either of these 2 compartments. To this day, it remains the only platform with this kind of capability. In our results to deliver best-in-class performance, we validated multiple methods available off the shelf like Bisulfite or newer enzymatic methods that deliver less lossy sample preps. And each time, reaffirm the superior capability of the Smart platform.

The core of that advantage is in maintaining the highest signal-to-noise ratio. We're maintaining maximum signaling molecules and effectively depleting the background to both minimize noise and stretch the power of our sequencing dollars. In addition to best-in-class performance, we've always been committed to delivering that wealth of data in a cost-efficient way. We have redesigned our automation platform with continuous flow batch processing, reducing footprint, hands-on time and turnaround time. This innovation will support our scale up and screening and overall efficiency across future upgrades across our portfolio. We're thrilled that this was possible for an active extraordinary complexity.

What has been exciting in the last 2 years is actually taking all of this and implementing within the suite of our products. We brought up Smart platform across the whole continuum of care that we provide. And jump started the data generation engine that powers our newest capability that you will hear a lot about today. Our speed of execution in delivering these product upgrades was remarkable, largely thanks to a very dedicated team but also driven by significant acceleration we're seeing by deploying AI tools across all areas of product development.

You will hear about Shield and Reveal in other sections and I'll focus on therapy selection for a while. With our tissue launch, assay innovation delivered multimodal data capture across RNA, DNA and methylation, returning maximum insights to the physicians. Moreover, we successfully developed that with minimum inputs, including challenging specimens with 92% less surface area and 40% less slides than are required for typical assays. This is a critical differentiating feature for Tissue NGS where rates of QNS quantity not sufficient or failed results remains high at 10% to 20% due to often scant amount of tissue material available.

For Guardant360 Liquid, data-driven innovation entire -- unlocked entirely new capability. While liquid biopsies have been adopted widely for some time for genomic biomarkers, most phenotypic biomarkers that tells how the tumor functions are only accessible through histology or direct analysis of the tissue which means limitations of scant amount of material, high QNS rates, but most importantly, lack of ability to easily access that information longitudinally as the patient progresses. Guardant360 makes it possible now to read out this phenotypic information from a blood sample.

This was made possible by accumulation of a wealth of data that you heard about from AmirAli and Helmy. We've seen 1 million patient samples. We're generating data at a scale close to 1 petabyte a week and we continue to increase the information density associated with every patient. In 2025 alone, we expect to generate close to 250,000 epigenomic profiles across our products. Moreover, over 40% of our patients would be sampled longitudinally with multiple time points during their patient journey, which means our database is going to be enriched for longitudinal tumor evolution and therapy response patterns.

This ecosystem, which Craig is going to talk about in the next section, enables our scientists to do discovery and validation of the novel multi-modal signature at unprecedented 1 million patient scale. We're at a point where data and science are converging to provide new insight from liquid testing. Molecular and real-world data with each patient defines a high-resolution map where patients sharing similar tumor characteristics clustered together. And as our database grows, we can map these patients with higher resolution and direct patients to the therapy with high likelihood of response. By integrating these diverse data sources and harnessing the power of Infinity AI against real-world data sets combined with genomic and molecular data to extract value from both structured and unstructured data. We've launched a suite of 15 new features and redefine how tumor phenotype can be accessed from blood. I will share a few of them now with you.

We have initially launched features that recapitulate no phenotypes, like tumor of origin and molecular tumor types like hormone receptor positive status in breast cancer. We're very excited about novel phenotypes that are currently in development. and promise to identify more patients eligible for treatment or trials or to predict response to existing approved therapeutics and expand indications.

Let me start with an example that is available in the clinic today through Guardant360 liquid test. While in some cases, tumor origin is known at the time of diagnosis, for too many patients, the disease has progressed too much, where the diagnostic workup requires a lot of time or is nearly impossible with current pathology work ups yet knowing tumor origin obviously alters the treatment pathway significantly. With Smart platform, we train ML and AI modals to differentiate methylation patterns observed in blood and provide confidence range predictions of the tumor origin. These predictions when made at high confidence recapitulate the accuracy of analysis that can be afforded with tissue NGS using RNA. Another exciting future application of that is actually tracking secondary malignancies during surveillance of early-stage disease patients who have increased risk of secondary malignancies. And in technology, we are often focused on precise analytical development but it's the stories of patients and providers like this one that helps us get inspired as we continue this work. In this case, our medical field reported a conversation with a key opinion leader in the GI cancer. For this patient tissue NGS was [ quantity ] not sufficient, so no cancer type production test could be used. IHC was inconclusive. Guardant360 came back 100% biliary. They said this was immensely helpful for human selecting first-line treatment for this patient and the treating physicians responded. This is really good. the results truly make a difference for this patient. I wanted to experience these things with us.

At a final resolution, it's not only tumor origin, but also molecular subtype of the tumor that defines optimal treatment. For example, hormone receptor status in breast cancer. It has been known for a very long time that these types are critical in putting the patient on the right treatment. It has also been known that as patients undergo treatment, their subtypes can change. Yet, there's no tools today that allows you to treat -- to follow that patients longitudinally and figure out when that transition happens. We have demonstrated with the Smart platform, ability to match these molecular phenotypes to their epigenomic profiles and identify clusters of patients that map, for example, to HR-positive status.

Now applying this capability to patient samples tested over time during treatment, we're able to offer longitudinal assessment of molecular types and they let physicians identify the right treatment for the right patient at the right time. With Guardant360, this is now available today.

And our next challenge, we're embarking on increasing clinical sensitivity of the Smart platform, for traditional genomic biomarkers with the goal of identifying more patients eligible for treatment through this wealth of data. Despite the success of liquid biopsies, some classes of biomarkers are notoriously hard to detect, especially when tumor circulation levels are low. That results in obviously missed treatment opportunities and trial enrollment opportunities.

We are discovering that many of these genomic drivers have associated methylation signatures that effectively allows us to rescue those opportunities by bringing methylation data into our algorithms. Let me show 2 case studies. In the first one, we valid ALK fusion. This biomarker is associated with 80% plus response rate. And so any missed opportunity here is a meaningful opportunity to impact somebody's life. Using Infinity AI against the database of 200,000 individuals profile longitudinally providing real-world evidence data into our databases. We identified methylation signature and demonstrated that we can rescue 40% of these samples that were missed by genomic testing alone.

In another example, we evaluated MTAP deletions. It is a biomarker that is widely profiled in early phase clinical trials in a pan-cancer setting and methylome surrogate signature identified 2.4x more patients than genotyping alone. These features will meaningfully increase the utility of liquid biopsy and provide clear advantage over genomic-only assays.

Finally, our most exciting new applications are being developed to address the major gap in precision oncology, where existing biomarkers do not fully explain response or lack of response within patient population. Richer information is needed to separate responders and nonresponders.

With the data density increasing as well as longitudinal follow-up maturing in our databases, our Infinity AI has uncovered methylation signatures, separating the groups of responders and nonresponders with higher degree of precision than current biomarkers afford us ability to do. We have demonstrated feasibility of these signatures across multiple biomarker classes and multiple cancer indications. And I'm really excited for you to hear the story from Craig in a few minutes.

If we pivot back to the practicalities of working with hundreds of petabytes of data, that gave rise to these powerful signatures. We clearly need to be thinking in a forward-looking way as to how this data can be effectively assessed and analyzed. Several years ago, Guardant has initiated and led a consortium to set the industry standards and protocols for working with distributed exabyte scale data engaging partnerships with experts in storage and file systems as well as other research organizations working with massive scale data sets. With this vision in place, put in several years ago, we're prepared to fully maximize the power of our data. In addition to this infrastructure, we've also invested to build our systems for integrated analysis of molecular profiles coming from our oncology patients, tested with Guardant products. and a symptomatic average risk screening individuals tested with Shield, all within the ecosystem of their clinical attributes and real-world evidence data. Craig will share some powerful examples of how this system was used to advance our validation in multi-cancer screening.

But beyond existing applications in oncology, we can now query patient cohorts of average risk asymptomatic individuals across more than 500 disease areas and associate their clinical history, comorbidities and outcomes with the methylation signatures we observed in blood. This drives the future diagnostics that expands into multi-disease screening.

With all of the excitement on the oncology side, I would like to also reflect on our progress in screening. We're encouraged by the recently released Shield CRC V2 performance data, which demonstrated 2x improvement on the analytical side that we talked about a while ago, and solid clinical performance with 62% sensitivity in Stage 1 colorectal cancer. To consider this work in the context, when we locked our Shield CRC assays, we had access to approximately 10,000 epigenomic profiles. With V2 approximately 30,000. With MCED development, we had access to close to 100,000 patient profiles informing our algorithmic backbones.

We estimate that by the end of this year, we'll generate 350,000 epigenomic profiles. We're committed to continue to deconvolve the biology -- complex biology associated with healthy background and early-stage disease and break the barrier of current best-in-class performance in the future.

As we think about the future blood-based diagnostics, we imagine a universe where more than ctDNA plays a role in unlocking new clinical applications or qualitatively changing the landscape of possibilities in oncology. If all diseases showed sufficient DNA, we're confident that our platform will be able to capture that signal. However, for the ones that don't, we're very actively exploring additional novel biomarker classes that could be additive to our existing platform.

Over the last few years, our research team evaluated over 25 different biomarker classes or measurement approaches. And critically, our rich biobank and [ databank ] and data interpretation power on top of that supports our ability to construct the right pilots and interpret the data we receive from our partners. While most of these pilots so far have not been able to add additional performance capability on top of our existing Smart platform today. We've taken several into Phase II and Phase III evaluation and are continuing to actively pursue them. The team is ready to act quickly should any opportunity emerge from either our internal R&D effort or those external pilots.

To summarize key takeaways, the Smart platform now fuels our entire portfolio, delivering high clinical utility and performance. By driving rich multimodal data acquisition with this platform, we created a data mode that now powers our Infinity AI innovation engine for creating new waves of clinical applications and constructing the cancer navigation map at a higher resolution. We believe in the power of our biobank and our databank to maintain leadership in early detection and expand into multi-disease screening. In short, assay-driven innovation created a data mode that now powers our data-driven Infinity AI innovation engine that will serve the next growth curve. Thank you.

With this, I'm happy to welcome Craig on stage. Hopefully.

Well done. So thank you, Darya, and hello, everybody. My name is Craig Eagle, and I'm the Chief Medical Officer at Guardant Health. The way we manage cancer is rapidly changing for the better. Building on the possibilities that our technology, that Darya just shared could help drive to patients a better outcome, I'm going to share some more examples of our excitement around how this technology can actually change the way we think about cancer and other diseases.

Clinical data is a key component to usher in any new innovation and any new ways of treating cancer. I'll cover with you some of the key facts that we continue and consider around data and give examples of the value of our technology to various stakeholders as well as sharing our data engine in more detail. You will see in the entire presentation today, key aspects of the results of our clinical research throughout the various sections. The clinical examples and data come from all aspects of our clinical research work. I'm delighted that we continue to be very focused and actively contributing to science that matters to patients and create a better understand in the biology of diseases.

One of the key strengths of Guardant is our learning engine on our data engine that spans across different data structures. So today, I will share a deeper dive on some of those aspects. Just to remind you that we continue to build our clinical data across the oncology care pathways. We now have over 1,200 publications and abstracts. Most importantly and most impactful are peer-reviewed journals, and now we have over 600 peer-reviewed publications, highlighting our technology across a number of cancer types.

Starting the top left. Of these peer-reviewed publications, we have partnered with more than 45 NCI designated comprehensive cancer centers, which is a testament to the quality and the strength of our clinical research. 31 publications have been used to obtain Medicare coverage. More than 235 publications have patient outcomes involving targeted therapies. And finally, 46 publications included in successful NCCN guideline submissions. So I've shared with you the current status of our clinical publications and that activity is ongoing around the globe.

I would now like to share how we will expand our impact using data. As previously highlighted, we have a differentiated clinical genomic and epigenomic database, consisting of claims data, longitudinal data and electronic medical records in combination with the results of our technology platforms. The data engine is building on the approach that as each commercial sample is tested, we have a methodology and a process that has been running for some time now that allows us to capture clinical data from those patients.

Our database, as shown on the right of the slide, now consists of 1 million unique tests and over 350,000 smart epigenomic profiles across over 100 tumor types. When combined with patient outcomes, it makes a powerful combination. Taking all this together and processing it through an analytical framework in this case, our Infinity AI platform, you can very quickly and very efficiently produce clinical data and tackle key medical questions in areas of unmet medical need. In addition, we have part with select companies that focus on similarly on using AI analytics and data to further strengthen our data engine.

This approach, you will see some examples shortly throughout the presentation, will increase the efficiency of relevant data being delivered to key stakeholders from the patient and the clinician to enable care decisions to regulatory bodies, pharma companies and payers. This data engine, an AI platform provides cancer and disease monitoring both at a research level and potentially at an individual personalized level, including monitoring their health journey.

Now I'd like to share some examples of the outcomes of this data engine just to give you a flavor of the possibilities that are found. So these are examples of the types of critical data and outcomes that can be produced and how this could change the way we think about cancer and were alluded to by Darya earlier. Starting with lung cancer. An epidemic Essentia can separate people that respond very well to immuno-oncology therapy versus those that have a poor prognosis and don't respond as well. And identifying these patients is beneficial for patient care and many stakeholders.

On the left, I have shown the ability of the current biomarker, tumor mutational burden or TMB to assess therapy prognosis with the blue line showing good prognosis group versus the poor group in the red. As you can see, the groups are really close, suggesting the biomarker does not distinguish these groups well. When you combine the traditional biomarker, TMB with epigenomics, from our smart liquid biopsy, you can see on the right side, the combination better identifies the different groups with greater separation of the blue and red curve. This creates a very powerful clinical marker that identifies good versus poor responder groups.

By identifying these groups, it enables potentially better targeting of treatment to the people that already have a good outcome. It also identifies a group where more therapeutic research into the poor group would now be possible. This, of course, is particularly interesting for the stakeholders like pharma companies. And this outcome and data is derived from our data engine.

And next, an example from colorectal cancer, using the same AI database engine, we can identify differential groups responding to a specific therapy, in this case, cetuximab, an anti-EGFR therapy. Currently, colon cancer treatment with cetuximab is based on which side of the colon the cancer is occurring. On the left, you get cetuximab. On the right, you don't get cetuximab. This sidedness of the biomarker determines likely response to that therapy. As you can imagine, that's a very biological in precise manner using cancer location to determine therapy. It is the only method available today.

When you start using epigenetics, you can delve into the biology more deeply. And what we find actually is left versus right is not as straightforward as we think. Assessing the data from the database, we find these very distinct epigenetic markers that shows those that respond to therapy well as shown again in the blue line and those that do not respond as shown in the red line. Interestingly, approximately 70% of the favorable blue line have their colon cancer on the right side. Create an exciting opportunity to get precision therapy to patients using epigenetics platform that by current guidelines right side of colon cancer, they would have missed out on this therapy.

Before I shift to screening, I just also can't resist the opportunity to share an example of our ongoing clinical trial work. I'm really excited to share but we are close to seeing the results from a trial, Pegasus, that has been ongoing for several years. Pegasus is a large prospective multicenter colorectal cancer chemotherapy de-escalation study. The study has 140 Stage III and high-risk Stage II colon cancer patients who normally all receive follow-on chemotherapy. In this study, using Reveal to evaluate the status of the colorectal cancer post surgery. Subjects could either be de-escalated from the usual chemotherapy or continue on standard treatment.

This is one of the first prospective clinical utility studies with therapy adjustments using tissue free, MRD in colorectal cancer. The final results will be presented at ESMO next month. So I suggest you look out for that presentation and see the results of that study. So I just want to switch back now after breaking from the database back to the database and focus, how this database helps in the screening area and demonstrate the power of the AI learning engine again with this clinical genomic and epigenomic database. Screening requires extensive and large data sets to demonstrate the impact of the device performance and also the impact of screening.

As a reminder, this is the outstanding performance for the Shield multi-cancer device and was presented earlier this year. Overall sensitivity of 75% at a specificity of 99%. The performance of the multi-cancer detection device was assessed through a case-controlled study run by the NCI where they provided samples from people with cancer and non-cancer. We did not know which was which. Effectively, we were blinded to the clinical diagnosis. We analyze the samples and return the results to the NCI. The NCI connected the Guardant test results with the clinical information, creating a rigorous assessment of our device performance by an independent expert institution, the NCI. These are the results you see here.

Please note this analysis includes both cancer positivity and cancer side of origin. The combination provides more information for doctors. And just let me explain a little bit more about the cancer site of origin or CSO. CSO is the next question in anyone with a positive multi-cancer detection test. Where does the cancer signal come from? Epigenetics is able to solve the cancer signal or cancer site of origin or CSO. For example, the figure on the left is a person with a positive cancer signal without the ability to understand the cancer site of origin. The result is a nonspecific follow-up pathway. This increases the likelihood of missing smaller tumors as well as potential to expand the diagnostic pathway or have unnecessary testing.

Contrast this to the figure on the right. By returning CSO, tumor-specific diagnostic pathways can be used to provide more clear guidance for clinicians and patients and allow for more specific evaluation of the tumors of interest. Unnecessary follow-up on diagnostic testing from positive screening is reduced by CSO calling as well as removing the need to explore the whole body to find the cancer. This creates a better outcome for patients. In the Vanguard Study, the NCI designed 9 specific pathways based on CSO readout as an example.

Now I've shared the MCD device performance, I'm going to share even further data derived from the AI database engine. So how does this relate to the data engine? I'm excited to share the approach with this type of data. First, looking to our database, we identified the potential for multi-cancer detection data on nearly 10,000 individuals. When you think about it, the effort and cost to collecting 10,000 people in a study in a more traditional clinical trial manner compared to pulling data from a database. The impact is very different. Less effort, less time, more cost efficient and greater study numbers. In this case, the study was formed to assess Shield MCD device performance in the real-world setting in a very short time and very efficient manner.

The protocol outline is on the left and included people sequentially enrolled over a defined time that had completed a Shield test as this made available the breadth of the epigenomic data to run the Shield multi-cancer detection device. The endpoints were specificity and positive predictive value or PPV. Just to note, PPV is a measure of the likelihood of a positive result that it will actually show cancer. Clinical information and analysis was based on claims data. By using this approach to complement our clinical trial program, it has a potential to increase study sizes and starting number by more than tenfold at a fraction of the usual resources.

So what were the results? I'm very excited to share that the results from the study I described above. By using our database engine and running the protocol, we identified 9,251 people for inclusion in the study to assess the Shield MCD device in a real-world setting. You can see the Shield's MCD performance as assessed by specificity was 99%. This aligns with the early assessment from the NCI protocol. In addition, positive predictive value is 41%, meaning if the Shield MCD test is positive, there is a 41% chance that cancer will be present. This gives insight in the potential Shield MCD would have on a real-world population and insight into its potential impact through cancer detection.

We are expecting the Infinity AI data engine with the addition of data derived from the shield testing to rapidly expand and unlock and even give us further potential as you've recently heard. Just think as everyone has a Shield test, it creates a significant inflection point for the potential to address focused areas of unmet medical need beyond cancer.

Let me share the Infinity AI engine as we now are thinking about this asset. As previously mentioned on the left, we now have over 100 cancer types in our database and more than 1 million cancer patients tested. On the right, with the launch of Shield CRC there's already more than 500 diseases beyond cancer. We can take a similar approach to the Shield real-world data example by using epigenomics data with clinical data. Equally exciting, as shown on the left, is the database for screening and other diseases. The Shield platform database is on track to rapidly exceed 1 million people. This shows some of the diseases that are currently in the database. There are several autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease like Crohn's disease. And as our understanding of the immune system increases, epigenetics has potential to contribute to improved diagnostics and clinical categories. There's also diabetes, several cardiovascular-related diseases and similar to oncology today, we have the opportunity to explore the impact of epigenomics in these other disease areas.

With that, I'd like to call -- help me back to the stage after I do a summary slide. In summary, I just want to summarize that there is innovative way of using genomics and epigenomics in cancer and health. We are building a one-of-a-kind database. I gave 2 examples of lung cancer and colon cancer using the database and how can unlock greater precision through unique signatures to better identify responders and nonresponders. In screening, the approach demonstrates the ability to perform a rapid and efficient analysis of Shield multi-cancer device in a real-world setting with results aligning with the case controlled NCI study.

This is reassuring that we're on the right path for the Shield multi-cancer detection device. Finally, when adding shield epigenomics combined with patient outcome, the database engine becomes a major differentiator and gives opportunity to explore the impact of epigenomics in diseases and health efficiently and rapidly, and in addition, over a period of time as regular testing and screening becomes incorporated in the database.

Now with that, I'd like to call Helmy to the stage. Thank you.

[Presentation]

Okay. Well, thanks, Craig, for detailing our clinical work. Now I'll dive deeper into the oncology business now. Therapy selection market in the U.S. represents one of the largest opportunities in oncology with roughly 1 million advanced cancer patients and a total addressable market of about $10 billion. Guardant is leading the market with a suite of groundbreaking products, Guardant360 CDx, which was the first FDA-approved liquid biopsy in the space, and our newer products in our Smart platform, Guardant360 Liquid and Guardant360 Tissue representing best-in-class tests, giving oncologists a complete view of cancer and more importantly, differentiated toolbox to do more both across blood and tissue than anyone thought possible in the field. Together, these products have established Guardant as a clear leader in therapy selection, reshaping how advanced cancers are diagnosed and treated.

Let's take a closer look at the portfolio. Guardant360 CDx has a turnaround of under 5 days, and it really set the standard in the category with a series of firsts in the industry, including first FDA-approved liquid biopsy and remains a workhorse of therapy selection in this space today. Guardant360 Liquid, our flagship CGP test and the most comprehensive liquid biopsy in the market. It profiles over 740 genes with leading sensitivity. It's powered by our smart platform integrates genome-wide methylation and that powers over 15 smart apps today. Results are delivered on average under 7 days, which is also faster than any competitive product in this space.

And then Guardant360 Tissue, our newest edition and the only true multimodal test in tissue CGP space, it brings together DNA, RNA, IHC and genome-wide methylation all-in-one assay. With innovations like AI-powered PD-L1 and smart-enabled methylation coverage, it is positioned to deliver the same wave of novel first-in-class applications that drove the accelerating adoption we saw with the Guardant360 Liquid.

As we said before, we are the clear leader in liquid comprehensive genomic profiling. And here's how we see the market today. We see the market is about $3 billion opportunity with most patients receiving about 1 test in their lifetime today. And at present, the market is still very much weighted towards tissue, although liquid testing plays a major role now. Well, looking ahead, we expect this opportunity to expand to about $10 billion, with the majority of that growth coming from liquid testing. The reason is simple. Instead of a single liquid or tissue test per patient for lifetime we believe that the standard of care is shifting towards 4 to 5 liquid tests per patient each year, a massive increase in testing opportunities.

The reason -- trials like SERENA-6 with testing of breast cancer patients for molecular progression, tangibly demonstrate this exciting paradigm of frequent liquid CGP testing is very, very near. To state the obvious, this kind of frequency is only possible liquid testing, faster, minimally invasive and more scalable. And as the power and clinical utility of Guardant360 Liquid increases with the integration of smart apps, our data mode, Infinity AI, new applications are unlocked that drive further adoption and further accelerate our share gains. So let's dive a little bit deeper in terms of how our smart platform works and how it's differentiated from other products in the field.

We have multiple layers of very rich information that is coming from each patient across genomics, epigenomics, transcriptomics, proteomics and real-world evidence. And so we're able to marry the molecular data such as genomic and epigenomic information with the real-world evidence, which includes the type of drugs that patients were on, types of adverse reactions, treatment outcomes and so on. And combine that all together to see new patterns in the data, new diagnostic applications and new predictive signatures with our Infinity AI learning engine.

Ultimately, these novel discoveries are powering our ability to classify disease with much higher precision than has ever been done before. And as a result, is what you're seeing is the recent onslaught of our smart apps. And so in a remarkably short time, our Infinity AI learning engine has powered the launch of 15 applications as part of our Guardant360 Smart platform, and we'll soon launch -- will soon fuel the launch of many, many more applications as Darya highlighted.

And let me share an example of how this works more specifically. This is a circular tumor biology map that was introduced earlier by Darya. These are in every report that we have in Guardant360 Liquid. It's a unique visual language and sort of tumor biology framework that we've developed at Guardant. And as we essentially collect more and more multimodal information from patients, we can dramatically increase the number of patients in our database. We're able to map this tumor biology in higher and higher resolution, basically seeing the specific nature of a single patient's disease in much more detail.

And as shown here, as you move forward from left to right, you can see that we can map this breast cancer in increasing density. And so basically, as we go from testing thousands of patients to tens of thousands of patients to hundreds of thousands of patients and eventually millions of patients, we're able to essentially map the subtypes and subtypes of subtypes. And we call these almost micro subtypes. We call them methyl tumor types, and they're redefining how we classify cancer at a fundamental level. This allows us to pinpoint the particular nature of a particular tumor of a particular patient's disease and use that information to develop applications and predictions that are truly suited for that patient. This is what was imagined when the term precision oncology was coined many years ago, but is finally only coming to fruition with our smart platform.

And so in this sample, we can take this specific patient's methyl tumor type, run it through our Infinity AI learning engine against over 1 million patient samples and clinical real-world evidence to predict what outcomes for that particular disease may be with some of the available treatment options. And so this is what I mean by a data mode. This type of predictive power is only possible when you have hundreds of thousands of epigenomic data samples and treatment outcomes. And here are the outcomes here for that patient. And so this only gets better and better over time with each successive patient, we hope in the field. And it's really exciting to see the power of this platform and where it's likely going to go.

So as Darya highlighted, our smart platform is unlocking a wave of new applications that are driving real excitement in the field that was at ASCO a few months ago, and it was really exciting to see just how engaged KOLs were, the clinicians were in terms of some of these new applications that have never been possible before. Just at ASCO, we launched 11 of those apps in May, and we have dozens more in development that will roll out not just on Guardant360 Liquid but on Tissue as well as Reveal because they all share the same epigenomic backbone.

And what makes Smart powerful is that it turns a single blood or tissue test into far more actionable information. Each application build towards what we see as a GPS for cancer care, guiding physicians with the right insights at every step of the patient journey. As you just saw, the Smart platform has unlocked many new applications. What's important is these aren't just interesting scientific advances but they're positively impacting the growth trajectory of our business. With the introduction of Guardant360 and Smart, we've seen a clear acceleration in Guardant360 volumes. Over the past 4 consecutive quarters, volume growth has reaccelerated, some of the strongest growth we've seen in the Guardant360 franchise in years. This is a clear sign of excellent product market fit narrowing the adoption pattern we saw earlier with our biopharma customers when Smart was first introduced a year earlier. And this is only the beginning.

Looking ahead, we see 2 main dimensions of volume expansion in the U.S. in addition to continued market growth. One, continued share gains as Smart becomes even more powerful and two, rapid growth as physicians expand the use of Liquid biopsy beyond the first test toward repeat progression testing and monitoring. Applications like tracking tumor evolution, both histologically and genomically will make Guardant360 a routine part of care at each stage of the patient journey.

Of course, a prime example of this is of tracking tumor evolution through Liquid biopsies, is SERENA-6 trial sponsored by AstraZeneca, where Guardant360 was the enrolling assay. In this study, breast cancer patients were tested with Guardant360 3 to 4 times per year to detect the emergence of ESR1 mutations. When those mutations were identified patients were switched to a next-generation oral SERD before radiographic progression. This is a true paradigm shift. Instead of waiting for visible progression, physicians can now make proactive therapy changes based on molecular signals.

And while that trial focused on breast cancer with a prevalence of over 40,000 patients in the U.S., we believe the same model will likely become the new care standard across multiple tumor types over time. We believe this will result in an MRD like testing opportunity for Liquid biopsy in the therapy selection space, and we look forward to the potential approval of Guardant360 as a companion diagnostic for the drug.

Shifting gears a bit. Today, I'm really excited to share an important milestone for Guardant360 Liquid. We have recently officially submitted our PMA application to the FDA for Guardant360 Liquid, a critical next step on the path to FDA approval. This submission is more than a regulatory step. It positions Guardant360 Liquid to become our single flagship FDA-approved Liquid biopsy for therapy selection, further catalyzing adoption, simplifying our portfolio and strengthening our leadership position in this space. And with FDA approval, we also unlock the potential for ADLT status for the expanded test, which will create a pathway to improve pricing.

This marks another important step in the Guardant360 journey, bringing the most comprehensive Liquid biopsy on the market, one step closer to full FDA approval and establishing it as the new standard for cancer care. Now let's take a step back and look at the full cancer care journey.

Beyond therapy selection, there are 2 other critical patient segments in oncology where Guardant is making a huge impact. First is for early stage patients where detecting a residual disease can guide treatment decisions and for cancer survivors where monitoring can help, what we call -- can provide those patients quantitative peace of mind for detecting recurrence earlier. These moments are just as critical for patients as therapy selection, and they represent yet another major frontier for Liquid biopsy.

And so therapy selection is about guiding the right treatment today, the frontier of minimum residual disease, or MRD, is about ensuring the right outcomes for tomorrow. The opportunity here is enormous. In the U.S. alone, there are roughly 18 million patients who are either early-stage cancer patients or cancer survivors. This translates into a total addressable market of about $20 billion. Guardant is a clear leader in tissue free MRD and Guardant Reveal is the leading tissue free product in this space. This is one of the largest emerging opportunities in oncology, and we believe Guardant is uniquely positioned to lead it.

Let's break down those 18 million patients and why a tissue free solution is critical. First off, roughly 12 million individuals are more than 5 years out from surgery. For them, tissue is often impossible to obtain, which makes a blood-only approach essential. Furthermore, when tissue is available, tissue can be less relevant given tumor evolution and additional primaries. And accordingly, physicians often prefer the wider catchment, a detection approach like a tissue free approach can provide. Additionally, even in the adjuvant setting, 10% to 30% of patients especially in cancers like pancreatic or lung cancers, simply don't have usable tissue for a tumor-informed MRD test.

This is why tissue free is just not more convenient. It's actually the only way to serve a pretty significant part of the market. And despite the size of this opportunity, penetration is still under 3% across the industry, and so we really are just the beginning stages of this very exciting market opportunity.

Let me share more about Guardant Reveal. Today, we believe it is the most advanced and highest performing tissue free MRD solution on the market with market-leading sensitivity down to 50 parts per million. Built on Smart platform, Reveal delivers precise methylation-based tumor fraction quantitation, setting it apart from other approaches. And with an average turnaround time of about 5 days, it provides results faster than any other commercial solution in the market today which can be critical in guiding meaningful clinical decisions. Over the last 18 months, we've made strong progress in operational execution to drive greater volume growth for Reveal without adding to overall cash burn.

At the start of this year, we secured Medicare coverage for CRC surveillance at $1,644 per test. Since then ASP has stepped up meaningfully reaching about $600 to $700 per test in Q2 of 2025. We remain on track towards a $1,000 ASP target by 2028. We've also reduced the cost of goods by more than 50% with 2025 COGS expected to be around $500 per test. The combination of higher ASP and lower COGS has moved Reveal into positive gross margin territory today. Together, these exciting developments and improvements set up continued momentum for the Reveal franchise and support our broader path to profitability.

Now let's take a few -- let's look at a few highlights of the extensive clinical data that we are producing with Guardant Reveal. Earlier this year at ASCO, we presented results of what we believe to be the largest MRD clinical study presented to date. The N0147 trial was a stage III colon cancer study that consisted of over 2,000 patients and we saw that methylation-based tumor fraction from Guardant Reveal could accurately predict disease-free survival and related outcome measures much better than the standard of care. Furthermore, we're very excited for the additional clinical utility readouts such as the upcoming readout from Pegasus, which Craig highlighted earlier in just a few weeks at ESMO 2025.

We also recently submitted a breast cancer data package to MolDX for Medicare reimbursement for Reveal. And in this study, we saw 100% sensitivity for ER-positive HER2-negative breast cancer. In another study, we saw 83% sensitivity in the surveillance setting for triple-negative breast cancer with a very, very high specificity. Breast cancer is one of the largest indications in MRD, and we would point out that we are already experiencing very strong momentum with the Reveal in the breast cancer setting.

One of the biggest challenges in oncology today, though, is knowing in real time whether a therapy is actually working. For many classes of drugs and especially for immunotherapies, clinicians often have to wait months to rely on scans that don't always tell the full story. To this end, in the radio head study of 521 patients, Reveal was validated in its use identifying nonresponders more than 3 months before disease progression and before it was visible by standard imaging. This was published in Cancer Research Communications and was recently submitted to MolDX for potential Medicare reimbursement.

And while this is an important step in our vision of Liquid biopsy as a new care standard in therapeutic monitoring, immunotherapy is but one of many classes of therapies used in the field today. Traditional chemotherapy, for instance, is still used in over 60% of cancer patients and still no MRD or monitoring tests have been validated with this class of therapy to date. This lack of progress in the field has even caused some to wonder if perhaps ctDNA cannot be used to monitor certain classes of drugs. For this reason, we are excited to share we now have data showing Reveal can be used to monitor response across chemotherapy, CDK4/6 inhibitors and, of course, immunotherapy with validation of other therapeutic classes in progress. Indeed, by leveraging the epigenomic backbone of our Smart platform, we can stratify responders from nonresponders with precision across almost all the most commonly used therapeutic classes, all from a simple blood draw tissue free. To our knowledge, no other ctDNA monitoring tool has validated this broad scope of application across all major therapeutic classes in all solid tumors. We're also pleased to report that these results are being ready for publication and will be submitted to MolDX for reimbursement.

And so with this exciting data, new capability in hand, I'm thrilled to announce that later this year, we will launch Guardant Reveal for therapy monitoring. This is more than just an extension of our MRD platform we believe it will set a new standard for how disease is tracked and adaptively managed. So instead of waiting for radiographic scans, physicians will soon have a Liquid scan, a simple blood test that delivers a real-time view of how patients are responding to treatment. And when paired with Guardant360 Liquid, this becomes even more powerful. Together, they create a seamless system to treat, monitor and retreat patients again across successive lines of therapy. We believe this launch represents the next major step in making Liquid biopsy indispensable in everyday care.

So as we presented at the last Investor Day, we have tens of thousands of samples across multiple tumor types that we had banked for potential clinical validation of Guardant Reveal across dozens of indications. I'm proud to announce that we've made excellent progress around accessing those biobanks and have been diligently working on a number of these studies. For 2026, we plan a 10x increase in Reveal data generation and expect this to result in over 20 publications with many of these publications supporting additional Medicare reimbursement submissions. I'm very proud of our team that has done an amazing job in terms of securing relevant clinical studies, patient samples and working with key clinical research collaborators to be able to increase the rate of generated data that will help cement Reveal's place as the leading tissue-free MRD platform for years to come.

Diving more deeply into the specific studies indications we have planned first to support reimbursement. We are successful in achieving CRC surveillance earlier this year and recently submitted dossiers for breast and IO monitoring for Medicare coverage. We'll be submitting packages for chemo CDK4/6 inhibitor monitoring as soon as those publications are out. And not too far behind those are studies that will support indication expansion for Reveal in over 5 additional tumor types in both the adjuvant and surveillance settings.

Now I want to shift gears a little bit once again. One of the biggest remaining challenges we see in tissue-informed MRD testing is sensitivity. In many tumor types, especially in the low shedding tumor types, it's critical to detect cancer at ultra-low levels, well below 10 parts per million. But the reality is that despite these bold claims, we believe that none of the available tissue-informed approaches used today can reliably reach that threshold on true clinical samples. In fact, most current exome and even whole genome assays plateau between 100 and 10 parts per million.

That leaves a critical blind spot where cancer may be present but today's tests simply can't see it. Even at ASCO this year, many clinicians expressed the need for what they call ultrasensitive MRD tests. Hence, why we believe there is a clear need for a next-generation ultrasensitive tissue-informed MRD test that pushes sensitively much, much further. And today, I'm thrilled to announce the next leap forward. We've been developing a new test internally, and it's ready to push the envelope of what's possible in MRD. So we're introducing Guardant Reveal Ultra, a breakthrough that pushes tumor-informed sensitivity down to an unprecedented level, approaching 1 part per million. This new test opens a door to ultrasensitive applications in cancer care that until now were out of reach.

Let me share a preview of how this technology works. Guardant Reveal Ultra is built on our Smart platform and combines the best of both worlds, the best of our liquid and tissue technologies. The result is a groundbreaking new MRD test with unprecedented sensitivity down to about 1 part per million as shown in the figure on the right. Flexibility, Guardant Ultra -- sorry, Reveal Ultra is designed to fit seamlessly alongside the rest of our portfolio, and speed of ease -- and ease of use, results delivered rapidly and reliably using our tissue CGP technology that can work with even challenging tissue specimens. We look forward to sharing more details about this exciting addition to our oncology portfolio soon.

And now I'd like to share a patient story to give you a flavor of how our tests are working synergistically together. In April of 2022, 54-year-old women completed treatment for triple-negative breast cancer. Given our high-risk disease, she was under close surveillance for the next 2 years. During one of our follow-ups, PET imaging showed significant activity in her upper chest. Given this patient's comorbidities, the risks were too high to move forward with a tissue biopsy without additional data. So our oncologist ordered a Guardant Reveal test. Test came back positive signaling the recurrence of breast cancer and was later to be -- confirmed to be recurrent triple-negative breast cancer.

Given the recurrence, her physician was able to quickly order a Guardant360 test off of the same blood draw just using our portal. Guardant360 revealed promoter methylation of BRCA1, which no other tests in the market can do today. Based on this information, her physician treated her with TALZENNA, a PARP inhibitor. And within 3 months, the patient was no longer showing radiographic evidence of disease. This case is a powerful reminder of how our tests aren't just identifying disease earlier, they work together seamlessly, actively reshaping treatment decisions and driving better outcomes for patients.

And so now to summarize a few key takeaways in our oncology business. We're the #1 player in CGP today with accelerating growth, and we're continuing to extend our leadership position based on groundbreaking innovation from our Smart platform and best-in-class commercial execution. The Smart platform and the growing data treasury combined with Infinity AI is allowing us to rapidly develop unprecedented new clinical applications. We are making great progress around Reveal in terms of multiple indications supporting MRD and monitoring applications as well as a major inflection in data generation that will support even more submissions in the coming years. And we are the #1 player in tissue-free MRD and very excited to introduce Reveal Ultra as a best-in-class ultrasensitive tumor-informed MRD product.

Okay. With that, I'll hand it over to Chris Freeman, our Chief Commercial Officer for Oncology.

Thank you, Helmy. Good morning. My name is Chris Freeman. As Helmy mentioned, I'm the Chief Commercial Officer supporting the oncology business. And today, I'm going to talk about how we bring all these amazing novel technologies to the market and ultimately, how we can impact and change how cancer patients are treated.

So over the last few years, we've seen a rapid increase in demand across the oncology portfolio, particularly in the past 12 months since the introduction of our Smart platform. Importantly, we've been able to translate that volume into revenue growth. So I'm going to explain what we did commercially to accomplish that and what we have in store for the future. As Helmy mentioned, everything at Guardant is predicated on our best-in-class technology. We pride ourselves on having pioneered the liquid biopsy space and providing world-class lab operations. That's resulted in industry-leading turnaround times across the portfolio, which is a key point of differentiation to physicians who are making urgent treatment decisions.

We also take great pride in making these technologies available across the country to community oncologists. Since we last met, Guardant has made dramatic improvements across our core products. First, we significantly expanded the genomic panels for both our liquid and tissue tests, covering all guideline-recommended biomarkers. Second, we expanded our portfolio to include peripheral testing capabilities such as RNA, IHC, germline and that helps us accomplish our goal of providing a complete portfolio. And finally, as we've discussed today, we've begun to unlock the power of epigenomics and explore novel use cases that can only be realized through this technology.

By now, you've seen this slide a few times, and that is intentional. This slide depicts our commercial strategy and highlights our greatest advantage. Now that we've established Guardant's best-in-class technology across the portfolio, commercially, we've invested considerable time and energy into connecting our tests in a way that optimizes patient insights. Cancer care is complicated. And so we worked with the physicians to simplify the ordering process through ordering bundles, workflows and digital tools. And so far, we've seen a really positive reaction from customers who appreciate how these workflows align with treatment guidelines and their own standard of care practice.

As a result of these efforts, today, the vast majority of U.S. oncologists regularly incorporate Guardant into their practice. And in recent years, it's been exciting to see the rapid increase in the depth of ordering, not just across our individual product lines, but increasingly in combination through the mechanisms that I just described. So how do we continue to scale? We scale by bringing world-class commercial infrastructure to the market, and at Guardant, we're able to amortize that investment across the entire suite of products. I'm going to spend a little bit of time talking about some of these topics, but suffice to say, Guardant is extremely well established with our customers.

Since we last met, we've expanded our EMR footprint to over 1,000 accounts. That's resulted in significantly more digital ordering, which allows us to take advantage of some of the testing bundles and workflows that I discussed. We continue to set the standard for turnaround time, and we've had significant managed care wins, particularly with major commercial payers. As you saw from Helmy and Darya, we have quite a bit to talk about with our customers regarding the latest data and use cases for our test.

On an earlier slide, AmirAli showed a number of oncology launches. Over the past 2 years, that translates to a new product launch or major upgrade every quarter. Our rate of innovation in oncology is breathtaking. Therefore, getting in front of doctors to educate on these innovations is critical. We've worked hard over the years to provide an elevated customer experience, and as a result, have earned unprecedented access in the diagnostic industry. This allows our team to provide update on Guardant tests, coverage and various partnership opportunities.

And so why does the Guardant Health team get so much time with doctors? The formula is fairly simple. When you combine world-class products with a world-class team that leads to access. And we've been able to convert that access into physician demand across the portfolio. So now that we've driven demand, the next step is to ensure that physicians can order our tests and that they're covered by payers. I'm pleased to share the immense progress that's been made in establishing our digital footprint. Today, 2/3 of physicians can access Guardant Health tests through their health system EMR, and over half of our orders are received digitally. And this represents our fastest-growing segment, with continued room for expansion.

Earlier, I highlighted that our core products are covered for over 310 million Americans. But our work is not done. Guardant is committed to ensuring that all of our tests are available to patients who need them. In support of that goal, Guardant has helped drive legislation at the state level. In the past 2 years, 10 additional states have enacted biomarker legislation. Our team has been successful in states like Arizona, Louisiana, California in working with state insurance commissioners and patient advocacy groups to ensure that payers comply with these laws. So once we've established demand and we've helped provide access to the test, we need to ensure that we're paid appropriately for our services.

I'm pleased to share that we've seen strong ASP improvements across the portfolio. For Guardant360, we've had the opportunity to leverage Medicare price increases. As I mentioned before, we've had significant commercial payer progress with Anthem, Aetna, United and Humana now covering our tests. In addition to that, we've been able to increase the Medicare price for our tissue test. And with the inclusion of RNA to Guardant tissue, this provides additional opportunity for ASP increases. And then finally, as Helmy mentioned, we've secured Reveal coverage for CRC surveillance and have a number of ongoing submissions that could potentially drive that ASP further.

So we're very excited about the progress that we've made in the U.S. And now we're taking that same approach globally where there remains significant opportunity and significant unmet need, especially as it pertains to [ access ] for cutting-edge CGP testing. So across Europe and Canada, we've made progress with national reimbursement. Now this has been achieved in large part because of our strategy in establishing public-private partnerships with key academic centers in country, most notably The Royal Marsden lab in the U.K., which has led to recent NHS reimbursement for non-small cell lung and breast cancers.

As you know, we also have PPP labs established in Spain with Vall and are anticipating Gemelli in Italy to come online later this year. And across Europe, in part because of these efforts, we've seen either the approval of new reimbursement policies or the acceleration of national coverage negotiations. Outside of Europe, we continue to make progress in the Middle East and in Japan. In the Middle East, since we last spoke, we've struck a commercial partnership with Hikma. And then in Japan, Guardant360 is the only liquid biopsy test approved, and it has, as of just this week, 10 CDx approvals.

I'm proud of the progress over the last few years, both in terms of driving demand across the portfolio and driving additional revenue. However, this is just the tip of the iceberg. On the therapy selection business, moving to the Smart platform, we have the opportunity to leverage wave after wave of novel applications. Many of these applications will be unique to Guardant and help us to differentiate in this space. On the monitoring side, we're excited about the addition of an ultrasensitive tissue-informed MRD assay to complement our market-leading tissue-free Reveal test. And at the same time, we will continue to make commercial investments that make it easier for physicians to access our tests, inclusive of portal enhancements, continued EMR integrations and enhanced workflows.

Finally, we will continue to explore potential ASP runway with the ADLT opportunities Helmy just described. So in summary, we have built an incredible product portfolio over the last decade, spanning the entire continuum of care. At the same time, we've built a world-class commercial team and infrastructure. And as groundbreaking as the individual tests in our portfolio are, what's even more exciting is that all of these products share the same Smart platform and how that provides a unique competitive advantage. All of our tests from Shield to Reveal, to G360 work synergistically across the entire spectrum of cancer care.

Data collected from one test is seamlessly mergeable with data from another. It is effortless for an oncologist to [ reflex ] from Guardant Reveal to Guardant360 and back again creating a truly differentiated platform experience. And because the technology foundation is shared, the clinical information that we can derive is also richer and richer as physicians use more of our tests per patient. So this testing ecosystem and the insights it creates leads to a very sticky and unique experience. We look forward to sharing more as we continue to populate our testing ecosystem with clinical applications driven not just by a single product but by the entire platform.

With that, I will turn it over to Jaime to detail progress with our biopharma business. Thank you.

All right. Thank you, Chris, and good morning, everyone. My name is Jaime Boyle. I'm Senior Vice President of Business Development, leading our biopharma commercial business. I'm excited to share a deeper look at our business with the investor community today. Over the past 3 years, the launch of our Smart platform has been a true game changer for our biopharma business, driving innovation, accelerating adoption and fueling growth. Our biopharma business also serves as a key leading indicator for the clinical business. Because we work hand-in-hand with our partners at the earliest stages of drug development, we gain unique visibility into emerging biomarkers, new therapy areas and testing needs long before they reach the clinic. In other words, success with biopharma today helps to seed tomorrow's clinical growth.

This combination of performance and efficiency is a clear leader in the space, and we're just getting started. To date, we've achieved tremendous growth by partnering with over 190 lifetime biopharma customers, including 19 of the top 20 companies, allowing us to tap into a total addressable market of more than $3 billion. Our team has consistently delivered outstanding results. We're not only generating significant revenue, outpacing many of our competitors, but we're also doing so with strong margins that put us firmly on the path to sustain profitability. The launch of our Smart platform, coupled with our growing partnerships, has helped us to generate tremendous growth over the last few years. 2024 was a banner year for the business with 30% growth and 2025 is off to a great start.

We have delivered record performance in Q2 of 2025, and we're extremely confident in double-digit growth this year and beyond. As noted earlier, we've been offering our Smart platform to biopharma for several years now and over 50% of our volume is now being run on this platform. As Darya and Craig highlighted earlier, achieving true precision oncology cannot be achieved through genomics alone. A recent meta-analysis published in the Journal of the National Cancer Institute indicated a critical gap. While 60% of patients tested with NGS present with genomic alterations, only 15% to 25% ultimately receive a matched therapy. Therefore, many patients are still unserved even after comprehensive testing. This is exactly why we are so energized about the potential of epigenomics. Powered by our Smart platform, we believe epigenomics represents the next frontier, unlocking a wave of groundbreaking discoveries that can expand precision oncology to more patients than ever before.

Biopharma companies need a partner that can help them move faster and achieve breakthroughs. Our mission at Guardant is to help improve our partners' odds of advancing new therapies to market with our technology. There are several ways in which we can accelerate drug development with our best-in-class services. First, we have expertise in companion diagnostics with approvals across the U.S. and around the world. Second, as we've already mentioned, genomics alone is not sufficient for precision medicine. By providing genomic and epigenomic insights with our testing platform, we can fuel translational research and improve the likelihood of identifying and targeting the right patients.

Finally, our Infinity AI learning engine applied to our real world and molecular data can provide even deeper insights. I'll expand on each of these further in the coming slides. Expanding on our CDx track record, we are a leader in companion diagnostics with 22 approvals across the U.S., Japan and Europe, and we have a strong pipeline of new approvals that are coming soon. In the first half of 2025, we've already submitted multiple sPMA submissions and continue to execute on new partnerships with key customers.

As Helmy mentioned earlier, we're excited to share that we've recently submitted the PMA for a liquid assay on the Smart platform. This milestone marks an important step forward, helping us to expand the biomarker landscape with our partners. And importantly, it also represents a powerful catalyst for driving our clinical business, accelerating adoption, broadening our market opportunity and strengthening our leadership position in precision oncology.

To underscore our leadership in companion diagnostics, I'd like to highlight a powerful example. Guardant is proud to have partnered with AstraZeneca as the enrolling assay for the SERENA-6 study, which was recently presented at ASCO. This builds on our leadership as the first FDA-approved companion diagnostics for ESR1 in breast cancer, which we received back in 2023. The study itself is practice changing in many ways and reflects the innovative surveillance design, pioneered by AstraZeneca to help me reach more patients in the treatment class. This recognition not only reinforces the critical role of our CDx partnerships, but also demonstrates the trust that our partners place in us to help bring the next generation of targeted therapies to patients.

And we are not stopping there. Together with our partners, we are bringing novel utilization of ctDNA to other tumor types, expanding on the potential for breakthroughs that can transform care for thousands more patients worldwide. In order to further support global clinical studies and companion diagnostics, we launched our partnership with Adicon for biopharma testing in China about 18 months ago. Oncology testing in China is not simple. Specimens cannot leave the country and local labs may not have a consistent solution for China and rest of world testing. This partnership positions Guardant as a provider with a seamless solution for clinical trial testing and enables biopharma to extend their testing into China with the same technology partner.

We've engaged with over 30 partners and have over 15 of those already under contract. So as a result, we expect to grow significantly with volume expansion over the next few years. Finally, Adicon has established themselves as a credible and reliable partner, including successfully running multiple Phase III prospective studies. Our growth in companion diagnostics is fueled by our commitment to advancing science. Through our technology, we help translational researchers unlock new drug development strategies with genomic and epigenomic biomarkers to help improve patient outcomes and also expand label opportunities. Our current and future applications can offer multiple solutions, including a few of those that you see listed here, response prediction, enhanced patient identification, molecular tumor subtype identification, adverse event prediction and quantification for MRD and monitoring.

Historically, biopharma companies have had to navigate multiple partners to access this full range of solutions. However, today, by partnering with Guardant, they can access this full range of applications through a single platform. One example of an epigenomic application that our customers are keenly interested in is ctDNA monitoring for dose studies. Typically, optimizing dosing in a trial requires aggressive methods that may lead to patient toxicity. As illustrated by the figure here by using ctDNA clearance as a surrogate marker and identifying a point of ctDNA clearance with minimal dose, this publication with Amgen showed how epigenomic tumor fraction could be used as a proxy to provide faster and safer dose optimization.

Additionally, we are expanding our partnerships in new ways that provide even greater value. This year, we were pleased to announce a strategic collaboration with Pfizer aimed at using our platform across Pfizer's oncology portfolio. This includes using our assays in clinical studies around the world, evaluating the clinical utility of methylation applications and partnering on the development and commercialization of new therapies. Another way that we are deepening partnerships is through the expanded use of our data.

As you heard discussed earlier by Craig and Darya, we are using our data in new ways, including unlocking the potential of multimodal biomarkers. By applying AI to our massive genomic and epigenomic database, we can identify patterns and features that would otherwise remain hidden. Using this multidimensional approach to identify biomarkers can allow our partners to tailor their drug and biomarker for multiple angles along the drug discovery journey, including early-stage clinical development and trial design and launch. Essentially, our platform enables better precision.

As we look to 2026 and beyond, there are several growth drivers for our business. First, by unlocking epigenomic applications with our Smart platform, combined with AI, we are creating new paths for drug development and future revenue streams. Second, the addition of ultrasensitive MRD, as discussed earlier, will position us to accelerate and expand share in these markets. Third, the expansion of our Smart platform to tissue testing creates an opportunity with biopharma beyond liquid, strengthening us as a comprehensive precision oncology partner.

And finally, our growth in CDx partnerships will expand as we enable new biomarker discoveries and testing paradigms. In summary, we introduced our Smart platform to biopharma 3 years ago, transforming the industry and providing a major catalyst of growth for Guardant. With paradigm-changing companion diagnostics, the biopharma business serves as a key leading indicator of our clinical business. Additionally, the Smart platform is a catalyst for transformative partnerships, supporting biopharma across every stage of clinical development and empowering smarter and faster decisions. We can enable biopharma to identify novel biomarkers and customize drug development with our growing epigenomic database combined with AI-driven insights. Our biopharma business has achieved many firsts in the industry, and we are focused on shaping a healthier future for patients worldwide with our partners. Thank you.

I think I'm turning it back over to Zarak.

Thanks, Jaime. We're going to take a 15-minute break, everybody.

[Break]

Okay. Welcome back, everyone. It's hard to beat the exciting presentation that we had before the break. But I'm excited to actually do a deeper dive on our screening business and the future of cancer that we are envisioning. For years, we envision a world that everybody would have access to a blood test, a simple blood test to screen for cancer during annual checkups. And those days are not far away. From the very beginning, we built Shield as a multi-cancer detection platform, a platform that can detect and catch many cancers at early stage when they are more treatable. With that vision in mind, we built this technology stack.

We chose CRC as the first indication for Shield because of the attractive balance that exists in CRC market to meet a big unmet need of filling the gap in improving CRC screening rate and also a field, a cancer type -- screening for a cancer type that has a clearly established pathway for regulatory approval and reimbursement. To make sure at the end patient at scale would get access to this life-saving technology.

Let me first focus on CRC. And we are going to talk about multi-cancer detection after. Our pivotal study has showed that we have market-leading performance for blood-based testing of 83% sensitivity in detecting colorectal cancer at 90% specificity, which was published earlier in New England Journal of Medicine. The promise of this blood test for colorectal cancer screening has been to offer a more pleasant, convenient option and a new choice option for patients and physicians to have access to.

Shield got FDA approval as a primary screening option last year and right after that, we launched it just over a year ago. What we are seeing in the marketplace is over and over, the physicians are enthusiastically using Shield, ordering it and when they order it, patients complete the test. The adherence rate or the completion rate of Shield blood test continues to be more than 90%.

In practice, what we are seeing today with the Shield volume that we are running, 90% of the patients who have been tested are the patient who had no history of CRC screening during the last 5 years, which is a clear signal that our targeting is working, as at this time, we are targeting unscreened patient population. And in fact, those unscreened patient populations are getting screened with Shield. We have completed several studies now, some randomized with health systems, major networks in terms of how Shield is really helping them to increase the overall screening rate.

For example, in one large health system, the screening rate was just over 45% after many attempts of using different modalities over a few years to increase the rate of screening, and once Shield was added as a new choice in the menu, the rate of screening went up by 2x to almost 90%. Interestingly, another study shown in the right bottom. For the individuals who are overdue for screening, when the Shield was established as a choice for those patients among the other modalities, Shield was the test of choice for 65% of those patients versus 35% of the time for the other modalities combined, colonoscopy and stool tests.

We are very excited with these results as the near-term validation of the potential long-term opportunity that really Shield has to improve screening rate and really to capture a very meaningful market share of CRC screening in years to come. We are very pleased with where we are standing with guidelines at this time. In late May, early June, we were very encouraged to see that the National Comprehensive Cancer Network or NCCN, updated its CRC screening guidelines to include Shield. As you know, NCCN is the voice of oncologists and arguably the most respected body in the oncology field. This first national guideline inclusion give us additional confidence that Shield will be added to other national screening guidelines in the future.

We continue to expect inclusion in American Cancer Society guidelines later this year which would set the stage for the commercial coverage in over 10 states. We are confident about guideline inclusion by U.S. Preventive Services Task Force or USPSTF. But based on the latest development from HHS as it relates to USPSTF, we are not counting on it until late 2027 or early '28. This USPSTF guideline inclusion and incorporation into quality metrics as managed by NCQA is an important catalyst for widespread commercial adoption of Shield.

It's interesting that given the uncertainty around USPSTF timing and future, several stakeholders are aligning to encourage action by HHS on quality measures, leveraging alternative guideline bodies like NCCN and ACS. While we wait for USPSTF, we continue to build our base business in the currently reimbursable opportunity for CRC screening, which is massive on its own. Here is the snapshot of our outlook for Shield revenue for 2025.

As a reminder, we are not updating our 2025 guidance at this time until our next earnings call. We are currently expecting $55 million to $60 million in Shield revenue this year. And this will mark this launch as the most successful diagnostic launch outside COVID testing. We are on track to exit the year with over 250 reps fully deployed in the field. At steady state, we continue to have the plan of having 600 to 700 reps promoting Shield by end of 2028. And we continue to anticipate being the market leader in blood-based CRC screening with over $500 million revenue in Shield revenues in 2028.

Earlier today, we announced an exciting strategic collaboration with Quest Diagnostics to expand and accelerate access to Shield broadly in the United States. Quest provider clients will be able to order Shield tests and receive results directly through Quest Diagnostics connectivity system. This system is used by approximately 650,000 clinicians and hospital accounts. Then for the blood draw and the logistic, patient can go to the Quest 2000 patient service centers and 6,000 in-office phlebotomists. In addition, Quest national sales team will be proactively educate primary care physician and OB/GYNs about Shield, accelerating the awareness among Quest ordering providers about the value of the Shield.

We expect Shield to be available for physician order through Quest system in the first quarter of 2026. We will continue to process all Shield tests at Guardant and control client services, billing and reimbursement operation. And we would not expect any ASP or gross margin impact as a result of this partnership.

Now moving beyond CRC. As presented by our team earlier, at Guardant, we have access to a treasure of database across continuum of care. We leverage the vast epigenomic data that we have captured in this company in CGP, MRD and Shield screening and combine it with the clinical data and AI tools, and we are pleased with the progress that we are making on our pipeline based on that data treasury. We are incredibly excited with our announcement earlier today about the expansion of Shield to include multi-cancer detection.

So how would that work? In order for patients to get access to Shield multi-cancer results, their physician will need to opt in to receive the multi-cancer report. And the patient will need to authorize the release of medical records to Guardant Health. We piloted this workflow in several accounts recently, and we got overwhelmingly positive feedback and reception from the physicians and very strong participation by patients to opt in and also opt in to authorize the release of their medical records. So what happens then? With the launch of this initiative, you're going to have an established scalable platform for clinical generation on one side, which enables assessment of the utilization of MCD testing and MCD results in patient care. And also we provide a new avenue to expand patient access to multi-cancer detection, bringing this important innovation to broader patients who are getting tested by Shield CRC today.

This nationwide initiative is expected to reach hundreds of thousands of participants, making it one of the most expansive prospective evidence generation initiatives in the early cancer detection field. Now with this expansion of Shield to include MCED results and patient authorization to release their medical record to get access to those results, we are going to be positioned to even better grow our data moat. This EMR data is of high quality and can be used as a source of truth for regulatory-grade data since it gives us the details of patient cancer journey that we will not be able to get access to otherwise.

Consider a protocol like this on the left. People who are going through this journey, we can look at the MCED results finding. Is it positive and negative and look at different endpoints in terms of device performance, safety of the device, cancer state shift and the impact and the value of the interventions, which is going to be used on those patients. Also, this data engine, this high-resolution data engine would help us to power the next generation of Shield MCED development and technology improvement to go to other cancers and to go from just cancers to many other diseases step by step.

As a reminder, Shield MCED as a stand-alone test has FDA breakthrough device designation and has been selected by National Cancer Institute for using its landmark Vanguard study. And now we expect this Shield as Shield Commercial Scale and the amount of data that we are going to capture from the medical records would put us in a very strong position to build this high-quality regulatory-grade evidence about the performance and the utility of this test. While we are focused on cancer and many things that you guys are hearing today is about just oncology, Shield is a platform that can go well beyond cancer.

As you heard earlier from our team, we have already accumulated a robust data set of epigenomic signatures in hundreds of diseases in asymptomatic individuals. I'm excited about the strength of the pipeline that we are building. I'm excited about the vast opportunities which are ahead of us.

Now let me turn the presentation to Stephen to talk about our commercial operations strategy for Screening. Stephen?

Good morning. I'm Steve Murphy, SVP of Marketing for Screening, which is our Shield product. It's been about a year ago since we launched Shield. And we brought the first broadly accepted and distributed CRC test in the marketplace out. And at that moment, it was kind of like a watershed moment, not just for Guardant Health, but for the industry overall because you see for decades, it's been very difficult to get movement in adherence and CRC screening. The numbers have stayed stubbornly low for a long time. And Shield now becomes a new tool for doctors to use to try to increase those adherence rates.

As you saw from AmirAli's slides, it's working. We're hitting the unscreened and the product is out there. And it works because Shield is the more pleasant way to screen for colon cancer. It provides a modality that makes it easy for people who have been reluctant to get screened to want to get screened. And since we've brought that forward, we've had a -- hit a significant number of milestones, as you can see up on the screen. We've built a vast commercial field force. We've gotten coverage by Medicare. We've gotten ADLT status on our pricing. We've gotten the -- in our first set of guidelines, built a huge phlebotomy network, just kind of terrific progress even within 1 year.

There we go. So what's happened in that last year? Within this growth, we've seen consistent double-digit rate increases in test volume, including in our most recent quarter. And the revenue has grown significantly, both as a percentage and in absolute dollars. And we unlocked a milestone that was terrific. We were -- we became gross margin positive, which in the first 12 months. That was not haphazard. We made a number of decisions to help drive to that, including a very disciplined focus on reimbursable lives, some smart scaling decisions, and we got some pretty terrific pricing because of our ADLT rate.

What that confirms is that the decisions that we went into our commercial model are working. We're seeing the benefits come through within already our first few quarters of performance. And we're just getting started. We're in the very early stages of approaching this market. The opportunity -- this is just the CRC screening market, but the opportunity here is enormous. $50 billion in colorectal cancer screening market. Of that 120 million individuals, 54 million of them are unscreened. And this is the group that we've been making some great headway with within our first 12 months.

The scale of this highlights 2 things: One, the magnitude of the problem that we're trying to solve; and two, the opportunity that we have at Guardant Health to deliver value in this marketplace. So what is our approach and how are we going to go out and make a big impact in this market? Three things primarily, and it's very straightforward. We are going to leverage the strong value proposition of Shield. Shield is the more pleasant way to screen for colon cancer today. But we also have the highest performance of any blood test.

We have the industry's strongest adherence rates. And with our expanded indications into MCED, we now bring broad access to another product for coast-to-coast for Americans, which includes CSO capabilities, which Craig spoke about earlier today. Additionally, within our sales and marketing funnel, we are prioritizing reimbursable lives up and down throughout that funnel. And that's supported by a very scalable infrastructure as we grow. And then finally, we use very bold messaging to stand out in a crowded marketplace. You saw one of our ads in the video that just went up. And there's another one that's running out in the hallway as well.

So as we go out to capture this demand, the scaling has gone pretty quickly throughout the last year. We're on track right now to have a field force of more than 250 by the end of this year. That is deployed again against reimbursable lives to make sure that the revenue is flowing in strongly. And we expect that growth to continue in the coming years. To support adherence, we've built a national network of 40,000 phlebotomists. This is very important, again, because one of the core value propositions of Shield is the ease at which you can go into your doctor's office and get a blood draw. So making sure that we've got that full network, it strengthens the overall value, makes it very simple for the patient to go in and get the draw.

And I think one of the things that we announced earlier was our deal with PathGroup. So this is in addition to Quest. PathGroup brings us the ability to reach another 250 health systems in 25 states. It's another accelerator in our ability to reach more doctors and more patients.

We are integrating across the nation's largest EMR systems. This gets us directly into those electronic systems that doctors and health staff members use every single day. Getting into that workflow is a key part of ensuring that we make it easy for patients to get Shield as quickly as possible. We're live in Athenahealth, eClinicalWorks and Epic. And this is on top of the portal that we already have and then with our Quest partnership as well as our PathGroup partnership. It brings multiple options for HCPs to be able to order Shield.

We're using some very bold messaging. I think the headline here speaks for itself, and it highlights a core aspect of our value proposition. This is opening doors for us and getting us into the conversation. We take these -- we take this kind of core concept of a campaign, and we distribute it across a number of the sales materials that we have as well. And we're finding that it works. This does, in fact, open doors for us. And we don't focus it in any one particular area, but we distribute it kind of across the spectrum of the funnel to drive awareness, improve education and hit at the point of sale. We've got TV spots, which we've already talked about, digital ads, direct mail, an influencer campaign, which we recently announced in August.

These are designed to drive awareness, become top of mind. But most importantly, at the point of decision when the doctor and the patient are having the conversation about what screening modalities do you want, we want to ensure that Shield is part of that conversation. In March, we achieved the ADLT designation for Shield. This ensures premium pricing and margin stability for us for the coming years. We're already seeing the benefits of this. We're getting a number of the leading payers in the industry. We're getting reimbursements from them. And as Mike will show you later, the ASPs, I think, have been very strong with Shield, something that we've been very happy about.

On the expense side, we are developing a next-generation operating model with our goal to, again, continue to drive long-term profitability for the Shield product. We're applying AI-supported initiatives and evolving our service process to lay the groundwork for a strong, efficient commercial infrastructure. This operational model, coupled with the smart platform, will enable continued innovation while maintaining our efficiency. So what does that mean? We talked about the demand. We talked about our approach going to get it. We talked about the strong pricing that we get on the revenue side and our approach to scaling. Overall, the fundamentals of Shield are very, very strong. In fact, as Mike Bell will showcase shortly, we expect Shield to reach breakeven in under 5 years post launch. This is an exceptionally rapid pace in our industry.

So to summarize, in just 1 year, we've gone from a groundbreaking launch to a nationally recognized, rapidly growing commercial business. We've proven the clinical value. We've built a coast-to-coast infrastructure, expanded our offering to include MCED, and we've laid the foundation for sustainable growth through positive product economics. But we've just begun. Shield is not only transforming how colorectal cancer screening is delivered, but cancer screening more broadly.

And with that, I'll turn it over to Mike Bell, our CFO.

Thanks, Stephen. Good morning, everyone. Great to see everybody here. So I'm now going to walk through how everything we've talked about this morning relates to our financials and specifically how it's going to accelerate our revenue growth and our path to profitability.

Before I jump into the longer-term financial targets, I just want to remind you all that we're not providing color on the third quarter at this presentation, and we'll update our outlook for 2025 when we do our Q3 results on our next earnings call.

So now I want to take a moment to remind you of the 2025 full year outlook that we provided at our last Q2 earnings. We're driving very strong top line performance across all our business lines and expect total revenue to be $915 million to $925 million this year, which represents year-over-year growth of 24% to 25%. Our oncology business is on track to deliver 20% revenue growth, biopharma and data mid-teens growth. And in the first full year of the Shield launch, we're expecting Screening revenues to be between $55 million to $60 million.

We're making significant improvements to our gross margins across all of our products, and that's increasing our blended gross margin from 62% last year to 63% to 64% this year. And we're continuing to tightly manage operating expenses, which is helping us reduce cash burn for the third year in a row.

Looking deeper into our revenue growth for the last few years. We're really pleased that since our last Investor Day in September '23, we've seen a significant uptick in revenue growth, which has been driven by multiple factors. Guardant360 Liquid volume has accelerated 4 successive quarters since we launched the first SmartApps just over 12 months ago. ASPs have improved across all our oncology products. Our biopharma and data business has performed incredibly well over the last 2 years, and we're delivering increasing revenue contribution from our successful Shield launch.

Now looking forward, we are expecting all of our businesses, so oncology, biopharma, screening to contribute positively to our revenue growth over the next 3 years. In fact, given the strength that we've seen in the last couple of years, particularly with ASPs, Guardant360 Liquid volume and our biopharma business, we're now increasing our 2028 revenue target to $2.2 billion, which represents a CAGR of approximately 34% between 2025 and 2028.

Over the next few slides, I'm going to break out this growth across each of our different revenue lines. So firstly, oncology. We've seen a strong acceleration of oncology volume in 2025 with year-over-year volume growth on track to exceed 27%. Looking at the multiple growth drivers across the oncology products, we're confident that we'll continue to see volume growth at similar levels over the next 3 years. For Guardant360 Liquid, the continued rollout and adoption of SmartApps will be a key growth driver as we'll repeat progression testing and monitoring opportunities.

For Guardant360 tissue, we're already starting to gain traction with our recent upgrades. And with our best-in-class test, we feel well positioned to start to grow our market share in tissue CGP. For Reveal, indication expansion and increased commercial focus are going to enable Reveal to continue to be our fastest-growing oncology product. And as Helmy announced earlier, our new Reveal Ultra test is going to allow us to enter the tissue informed market with another best-in-class product.

On the ASP front, we've made great progress since our last Investor Day, reaching our 2028 targets for Guardant360 Liquid and Tissue, roughly 3 years ahead of schedule. As a result, we're updating our 2028 ASP targets. We believe we can continue to expand commercial coverage for Guardant360, which will lead to an ASP of $3,300 by 2028. For Guardant360 Tissue, we believe we can increase the ASP by 50% to $3,000 by increasing commercial coverage, improving the pull-through of Medicare Advantage reimbursement and by expanding reimbursement for the tissue RNA test that we launched last quarter.

For Reveal, we've made very good progress with ASPs over the last couple of years, and we're still confident that we'll achieve our $1,000 ASP target in 2028. And that's going to be driven by Medicare coverage for additional cancer types and by expanding commercial reimbursement.

Finally, we're pursuing ADLT status for Reveal, and we intend to pursue ADLT for Guardant360 Liquid and Guardant360 Tissue. If we're able to obtain ADLT status for any of these oncology products, it's going to be upside to these targets.

So putting oncology volume growth and ASP expansion together, this gives us a lot of confidence we can continue to grow this business with a CAGR of approximately 30% over the next 3 years and achieve oncology revenue of approximately $1.4 billion in 2028.

Okay. Moving on to Biopharma and Data. So as Jamie outlined, this has been an incredibly strong business over the last 2 years, and we continue to believe it can deliver double-digit growth each year between now and 2028, which would result in revenue increasing from approximately $200 million in 2025 to approximately $300 million in 2028. As well as generating strong gross margins and positive free cash flow, our biopharma business provides significant value from the pharma partnerships that help fuel our product innovation, the companion diagnostic approvals that drive clinical volume growth and the global footprint that supports our international expansion. Finally, our data business bolsters our Infinity AI capabilities.

Now moving on to Screening. At our last Investor Day, we gave screening targets that were based on a set of assumptions that have listed here. We're really pleased that 2 years later, we're tracking to or ahead of nearly all of these assumptions. We achieved FDA approval in 2024 as expected, albeit with an advisory panel thrown into the mix. We achieved a first-line FDA label where our base case assumption was second line. We gained ADLT status. That was expected, but at a rate of $1,495, which was higher than our previous assumption of $920. As a result, our 2028 ASP target has increased from $500 to approximately $700.

We assumed Shield would be a single cancer test in the period up to 2028. But as we've announced today, we've expanded beyond CRC to multi-cancer. Finally, the one assumption we'll miss is the timing of USPSTF guidelines. We originally expected Shield to be included in those guidelines in 2026. But given the delay to the start of the USPSTF review, we're now assuming guidelines are going to come in 2027 or 2028. Regardless of the change of those -- of the timing of USPSTF, we're now even more confident that we can achieve the screening target that we set at our last Investor Day, which was to generate more than $500 million revenue in 2028.

So summarizing our total revenue target again with all the growth drivers across all the areas of the business, we're increasing the 2028 revenue target to $2.2 billion, which represents a CAGR of approximately 34% between '25 and 2028.

Okay. So now I'm going to go down the P&L. And first of all, turning to gross margins. We've made great progress reducing testing costs over the last 12 months. But Reveal and Shield -- both Reveal and Shield COGS have been reduced dramatically from over $1,000 in the middle of 2024 to now below $500 in Q2 of 2025. Looking forward, COGS will continue to reduce across all our portfolio as well as the positive impact we'll get from the volume increases with many ongoing COGS reduction initiatives. For Guardant360, we've already begun the transition to NovaSeq X. This will complete sometime next year, and it will initially offset any increases in the sequencing costs due to the expansion of the SmartApps.

But over time, this transition is going to lead to an overall reduction in Guardant360 COGS. For Guardant360 Tissue, we focused on operational efficiencies and leveraging the lab infrastructure we've built for Liquid. And for Shield, we're implementing workflow efficiencies similar to those we recently made with Reveal, and we're investing heavily in automation. When these changes have gone through FDA review, they lead to significant step-downs in Shield COGS, and that's going to help us get to our target of $200 COGS in 2028. Finally, we're planning to implement the same automation for Shield into our MRD lab and further reduce Reveal COGS. With these COGS reduction initiatives and our new ASP targets, we believe that we can continue to improve the blended gross margin, and we're targeting a range of 65% to 70% in 2028.

Since our last Investor Day, we believe that we've made -- we've successfully balanced tight cost control while still making significant investments in both innovation and commercial expansion. We've reduced R&D spend, and at the same time, we've successfully launched innovations such as SmartApps and major tissue upgrades. We've completed the ECLIPSE study and gained FDA approval for Shield, and we've developed a multi-cancer screening test and an ultrasensitive tissue-informed MRD test.

We've kept our G&A spend flat, leveraging infrastructure while expanding the complexity and scale of our business. And we've strategically invested in the sales and marketing line to support growth across Oncology and Biopharma as well as successfully launching Shield and building out our Screening PCP sales channel. Looking forward, we intend to continue to be thoughtful and strategic on how we allocate capital, how we maximize leverage across the business and how we build out our commercial capabilities.

One major area of focus for us is AI efficiencies. We're already utilizing AI across many functions for some, such as software and technology, we've been at the cutting edge of AI for many years and can continue to get better and better. There are many high-volume, high-touch functions such as reimbursement and client services, where we've now started leveraging AI, and we see a clear pathway to significant reductions in cost per transaction as we scale the business. We're also very excited about the opportunity to start to integrate AI into our sales processes. And we see this as something that will give us significant efficiencies and cost savings as we build out our commercial capabilities and screening. And across the G&A lines, we're starting to implement AI solutions in finance, legal and HR and have many ongoing initiatives to maximize AI efficiencies where possible.

And finally, although we all love Zarak, maybe one day, there's a moment where you guys are calling him up and you're going to be answered by an AI agent. That sounds exactly like him, but maybe that's a few years down the line, we'll see.

Okay. Now turning to cash and the path to profitability. We've made good progress over the last few years on our commitment to reduce our free cash flow burn every year. This year, we're on track to bring our cash burn down to between $225 million and $235 million. Going forward, we intend to continue to reduce our cash burn each year. Furthermore, given our improved revenue and gross margin targets, we're bringing forward our time line to breakeven by 12 months from our previous target of the end of 2028 to our new target of Q4 2027.

To help understand our path to profitability and because different parts of the business are at different stages of maturity, it's useful to talk about cash flow specifically for screening and cash flow for the rest of Guardant, excluding screening. So screening is still in its scaling phase. It's in the early days of the Shield launch, and we're building our commercial infrastructure to maximize our first-mover advantage. We'll continue to increase our sales and marketing spend and to reinvest all of our gross profit from Shield during 2025 and 2026.

As a result, we're expecting screening burn of approximately $200 million in both 2025 and 2026. However, we expect to reach an inflection point in screening during 2027 as the gross margins will start to drop to the bottom line and start to rapidly reduce the screening burn. As Stephen outlined earlier, we plan that screening will reach cash flow breakeven when the Shield revenue run rate is between $600 million and $800 million. For the rest of Guardant, so that's excluding screening, we're well on track to reach cash flow breakeven by the end of this year. And from 2026 onwards, the rest of Guardant, excluding screening, is going to generate increasing levels of positive free cash flow each year.

We know how critical it is to reach company-wide breakeven and to begin to generate sustainable, profitable revenue growth, and we have every confidence we can get there sooner than we previously planned.

Okay. So summarizing the financials. Firstly, we're executing ahead of the financial plan that we laid out at the last Investor Day. We're increasing our 2028 revenue target to $2.2 billion. We're targeting gross margin expansion across all our products. We're balancing investment in commercial expansion and innovation with maximizing efficiencies, AI and leverage. And finally, we brought forward our free cash flow breakeven guidance by 12 months.

Thank you. I'll now hand over to Helmy and AmirAli to wrap up.

So as we wrap up, let me leave you with a few highlights here. We've built a world-class innovation platform with smart and Infinity AI, and it's accelerating the pace of science and product development. Our oncology business is growing faster than ever with SmartApps fueling therapy selection and Reveal leading the way in tissue-free MRD. Our Biopharma partnerships remain strong and are helping to accelerate drug development for our partners in new ways. And Shield is proving to be a blockbuster in blood-based screening with multi-cancer detection on its way. So the message is clear. Guardant has the science, the data and execution to keep leading. We're proud of how far we've come, but even more excited about where we're going.

And maybe just actually highlighting one more time the new announcements that we had today, increasing 2028 revenue target from $2 billion to $2.2 billion, accelerating company-wide breakeven to Q4 of 2027, 12 months ahead of previous guidance, submitted Guardant360 Liquid PMA to FDA, launching Reveal for therapy monitoring in Q4 of this year, increasing Reveal clinical data generation by 10x in 2026 and expectation of having more than 20 publications in 2026. [ Tushin ] informed Guardant Reveal Ultra with sensitivity down to 1 PPM, expanding Shield to include multi-cancer detection findings, initiation of a large-scale study of real-world data for Shield multi-cancer detection and finally, strategic collaboration with Quest Diagnostics to expand nationwide access to Shield.

We are here for one reason, curing cancer with data to give patients more time with what matters most for them. Whether through MRD peace of mind, whether through Shield early cancer detection, whether by just simply turning results hours earlier, every moment we save allows patients to have more time for life's precious moment. Our success proves our approach works, and we believe we are just getting started.

I guess now you're going to see the beginning video, right? Yes. We are not going to read through the whole thing one more time. So beginning video.

[Presentation]

Speakers, please return to the stage to commence the Q&A portion of the day.

Okay, guys, we're going to start Q&A for about 45 minutes. It's going to take questions on mostly an ad hoc basis. There's going to be a strong preference for anyone that's wearing their socks from the '23 Investor Day.

Dave? Mark? Mark Massaro? Good. Yes, Kelly and Carrier are in the audience, they are going to be running the mics around. Maybe we'll start -- let's do that. Are you ready, Mark? Okay. Go for it.

Congratulations on a good Analyst Day and increasing the targets. I wanted to start with the assumptions on the Shield. With respect to the fact that you're increasing your ASP from $500 to $700, why $700? You're obviously tracking ahead of that now. And then I also wanted to ask a question about with Quest coming on and you have other positive momentum going on in Shield, why did you choose to maintain the Shield revenue target when there's some other -- so I guess implied is perhaps lower volume assumptions? Or can you walk me through any changes?

I'll take that. Yes. I mean, firstly, with the ASP. So yes, I mean, currently, our ASP is over $900. Stephen talked through how at the moment, we're really focused on reimbursable lives. So this is where we're getting reimbursed by Medicare, Medicare Advantage. We know that as we go forward and we start to get into ACS guidelines, USPSTF guidelines, then we'll be opening up the market to patients below 65. And while we're very confident that we'll get strong reimbursement from those commercial payers, it's going to take time. And so for a while, I think there's going to be some commercial volume that's getting paid, maybe at a 0 as it takes time for those patients to come on board or a bit lower.

So when we look at this, we're really pleased that the ASP is going to be higher than our previous target. We think 700 is a good future-looking target for 2028 when we're sort of in that transition of just adding on more and more commercial payments. I don't know, AmirAli, if you want to talk about the volume.

In terms of volume, we want to actually we confirm our long-term guidance almost without the impact of USPSTF. And then if it happens, it would be upside if it would happen sooner. And we don't want to get too ahead of our skis. We are very pleased with the way the launch has gone so far and excited about our rep productivity. We are also very excited about this commercial and channel and distribution partnerships that we are doing, but we didn't take that into account in terms of the upside until we learn more in terms of how the impact of that would be, but potential could be vast step by step.

Dan Arias from Stifel. I guess a question maybe for Darya. I wanted to ask a little bit about AI. It seems pretty clear that that's going to be an important part of what you guys do well going forward. How much of what you have working for you is due to sort of a commercial offering, something that's accessible to your customers -- sorry, your competitors versus something that's developed in-house? Essentially, what -- to what extent would AI be sort of a secret sauce for you versus other oncology organizations that can take a service offering and do something similar?

Thank you. So I think it's a landscape that includes multiple options here. There's definitely internal development effort that's looking at how we can maximize the value of that data and analysis in site using pretty complex multiparameter, multibillion parameter type models. We have seen initial baby steps in that direction. We're usually very careful with data and interpretation of that data in the context of multiparameter models, and we want biology to guide a lot of that.

We're seeing ability to use higher complexity models now that we have developed a database that stands for itself in terms of being able to service these multiparameter models. We're looking at both partnering with others in developing some of these models and internal development effort to materialize that value. So time will tell exactly which paths proved to be more successful.

Maybe Puneet Souda from Leerink.

Excellent presentations by the team. One of the key questions -- one of the key points here was, is simply the ease of use of a blood test. And you clearly highlighted that there's a DTC campaign ongoing. And I just want to understand, can you talk a little bit about the focus on DTC? How much of -- how much spend are you thinking about that into the next year? And the number of reps, which are 250 by year-end, how would -- how can they expand to catch that as that DTC campaign? We have obviously seen successful examples in colorectal cancer screening space with DTC. So I just wanted to understand that point.

And then maybe, AmirAli, I would love to get a high-level point, but more -- I would say, a simple question is really that investors want to get a better understanding is -- given everything that you're seeing so far with the adoption of this assay, how should we think about the penetration of blood screening in the 120 million population in the U.S.

Maybe I'll start some high level, then I ask Stephen Murphy to talk more details about the DTC question and then maybe I end about like where I think the terminal value of blood-based screening would be. So right now, actually, we are obviously very excited with how this launch is going. Our main focus has been our campaigns toward our -- the health care physicians, the HCP front, more than consumers. We are doing some piloting programs though, like with some of the ads that you guys have seen. And we are aggressively investing on building the distribution channel on the sales force side.

Maybe I'll give it to Stephen to tell more about some of that.

I think on DTC advertising, there's a couple of things that -- outcomes that you look for. Who can drive in and convince their doctor to start offering Shield and then who goes into an office where Shield is already offered. So part of what we need to do is make sure that we've built the pyramid where you've got the HCP advertising driving HCPs to join and offer Shield alongside that consumer. So it will build up kind of together. We lean a little bit more into the HCP side today because it's a better optimization of spend when you see it overall.

There are some actually interesting technologies these days that years back did not exist sometimes like you can go and target consumers within the practices that you have channels or their active orders of Shield today and specifically target those patients in your DTC campaigns, which brings a lot of efficiency in some of the pilot programs that we are doing. Maybe now talking about like long term, the way we think about Shield value.

When you look at CRC market, when there are more than 50 million people unscreened, when there were other modalities for a decade or 2 decades out there and still all these patients are unscreened. And when -- I showed some data earlier during the presentation, when Shield was introduced in some large health system, which they had campaigns like care gap campaigns, and they are dealing with this level of unscreening, the screening rate went up to almost 90%. That gives us a lot of actually validation of the potential long-term opportunity that Shield has in terms of the overall market share of CRC screening.

So in like another study I showed 65% of the patients who are overdue for screening are picking Shield versus 35% all other modalities combined. So sometimes I get the sense, sometimes people are getting confused that they look at it, okay, like almost like a therapeutics kind of mindset that, hey, maybe this is which line of kind of thinking it is for patient and then the opportunity gets smaller and smaller, smaller versus this 54 million unscreened patient population is the biggest piece of pie, which is completely untapped.

And I think over time, we see what happens with the rest of modalities. Definitely, we believe the best-in-class test is colonoscopy. And this is for CRC. Just fast forward, envision a blood test that can look at different cancer types, different diseases. I think many people would like to get that test even beyond CRC screening in terms of the values of such test.

Let's see what's on Doug Schenkel's mind.

Okay. Thanks, everybody. This is a really fun and informative day. So thank you for all the information and all the effort that went into this. Where is Helmy? Helmy, I'm going to start with you real quick. It seems like you didn't include a lot of sources of upside to your ASP expectations. When I think about ADLT status in G360 blood, seeing where you guys are priced relative to some of the new competitors in Tissue, the possibility of Reveal ADLT, it seems like the error bars skew a lot to the upside there.

Either you, Helmy or you, Mike, any chance you'd be willing to quantify how much you think you've kind of left on the table as a potential source of upside there? And then I don't want to leave you out, AmirAli. So I'll have one quick follow-up there.

You're not incorrect. Mike.

Yes. I mean it's -- so first of all, yes, the ASPs that we laid out don't include any ADLT upsides. And so if we were to achieve those for any of the products, and again, we said we're pursuing Reveal now, and we intend to pursue it for Guardant360 Liquid and Tissue, then obviously, that would be an upside. We know, for example, with Reveal, our cash pay price is $3,500. Current reimbursement is $1,644. So we would have a nice upside there. With respect to Guardant360 Liquid and Tissue, obviously, that's going to depend on where the price is. But yes, I mean, we would hope for upside.

I don't think we want to sit here and say exactly what that would be. We think the ASP targets that we set out today are very strong ASPs anyway. They're going to improve our gross margin. So yes, anything on top of that is going to be very nice upside.

All right. I won't push on quantification, but that's enough for us, I think, to do some math. So thank you for that. AmirAli, blood is easier than stool in colonoscopy. Do you -- have you seen data that suggests as we just think about as a community trying to get the overall compliance rates, I mean, recognizing CRC screening percentages have been stubbornly low. Do you have data that suggests adding MCED to CRC actually gets compliance higher for overall CRC, meaning blood will help alone, but just adding MCED, do you think that gets people to basically say, okay, I'm going to get screened.

We are not counting on that, obviously. Like the reason we are expanding Shield to have this MCED findings is additional value that we can offer to the patients. Just imagine actually when we are getting patients tested for CRC, and we are seeing the sign of the patient looks like have ovarian cancer, at least with some post this probability now. We have tremendous value for patients if they are open to it and physician open to it to get access to that potentially life-impacting information. That's the way we look at it, and we are going with that vision of even multi-cancer, multi-disease to offer more value on the table for patients.

Kelly, let's see if maybe there's an investor on the side of the room that has a question. Yes, maybe Dave Westenberg from Piper.

I'm going to stick with Shield a little bit expansion of what Massaro was asking. So first, I want to talk about the V2 version because the overall sensitivity only went up by 1%. But I would argue the performance was much better because of the Stage 1. And then you actually had a skew towards Page 1 that you kind of didn't talk about. So can you talk about the performance there? How fast can that we be switching to that assay?

And then secondly, you answered a lot with Mark's question. But on that $500 million in revenue in 2028, that is a pretty steep ramp. Do you see a step function change in revenue growth as new indications hit? And I just want a clarification. I think you said U.S. Preventative Services is not necessary. Can you clarify if you did say that? I thought you did. And kind of what's the ASP assumption kind of ramp as we get to '28?

Okay. So I'm pretty sure I'm going to forget some sections of that question. So maybe about V2, I say something and then maybe I pass it to Darya to add. V2 Stage 1 performance improved. We knew it had 2x higher analytical sensitivity, and that's why Stage 1 kind of moved. And the rest of it, I think, is just a matter of sometimes the cohort that you deal with, right? So we take it as a small win, 83% to 84%. I think it tells us we are on the right path, and we'll see over time through additional data, additional insight or other multimodal that the team is working, what we can do. Darya, do you want to add anything? Yes.

Okay. Then the second one about maybe USPSTF and $500 million. So the USPSTF and quality score inclusion is a big catalyst for the widespread adoption. No question about that. But we want to make sure just based on what we are seeing and the delay, although there are actually some good alignment between different stakeholders. And if you are interested, maybe we can talk about that. In terms of like maybe what can be done with the process, we wanted not to count on it until late '27, early '28.

And once it's late '27, early '28 until the commercial payers start to adopt it and payer coverages start to change effectively in this LRP window that we are talking about in 2028, we are not counting on it in terms of any material contribution. So that's the way we thought about this revenue. And we are -- based on what we are seeing, we are confident we can exceed that $500 million target that we mentioned before. And I forgot already the rest.

[indiscernible].

Yes. I mean I think...

In terms of contribution [indiscernible].

Oh, you mean with the addition of multi-cancer. Yes. I mean we're just really focused on the reimbursement that we get from CRC. So we've not built into the model any incremental reimbursement from adding any other cancers. Maybe down the line, when this has gone through an FDA -- multi-cancer has gone through an FDA approval, there may be some opportunities then. But I think we feel that with the $1,495 that we get now and the strong gross margins, that's enabling us to still be able to offer that multi-cancer report, and we're not seeking additional reimbursement for that.

Maybe Pat Donnelly, Citi.

Yes, Patrick Donnelly from Citi. Maybe, AmirAli, just on the Shield piece, obviously, a lot of market moves over the last month or so. I mean has the Exact-Freenome combination changed your view at all in terms of the level of investment necessary? I think Mike talked about reinvesting all the gross profit proceeds over the next couple of years. Just in terms of continuing to build that moat where you guys have the market to yourself. Obviously, the time line shifted around a little bit. Just curious if that changed your perspective at all, both on the investment side and then just the competitive landscape.

On one side, we are reaching our competition, best of luck in the process they're going through. And it's good for marketplace sometimes to have multiple players to open up the market faster. We thought actually maybe the field could be potentially 3-player field. Now it looks like maybe at most would be 2 player for many years, and we see how it goes. We believe this level of investment that we are doing, Shield is more than adequate to go after this opportunity very aggressively. And this kind of the spend that we are talking about, it's been in place now, I don't know, maybe over 1.5 years now, 2 years almost. So we are continuing to have that mentality.

And I don't think we are underinvesting, like this is such a big opportunity that it would not be wise to underinvest when we have such a long lead time. But I think it's adequate level of investment, and we are aggressively growing our commercial infrastructure. And I think when you think about where we would be by end of 2026, our own channel, partner channels that we just talked about 3 of them during the last couple of weeks. It's a solid footing.

When you think about EMRs, we are building those ourselves. And now through this Quest partnership, again, we have access that one connection with Quest is going to be connected to 650,000 ordering physicians. We probably saved a decade of work there through this partnership. So a very reasonable cost, in fact, for us. There's a lot of good brand equity of Shield that gives us a lot of opportunities to access to that we didn't even envision 2 years ago. Many people want to be around the table with us, which is very fortunate. So we are very pleased and more confident than ever about the prospects of this brand.

Kelly Hans has a question from [ Federated ].

[indiscernible].

Hans, microphone since we have people on Internet.

If you want to reach the 100 million men who haven't been tested for CRC, the easiest way to get there is to have one ad in the Super Bowl, every men watches it. Their revenues just went through the roof. It just a thought, very expensive, though.

Thank you for sharing your vision. It definitely something we thought about. But yes, step by step.

Let's try, [indiscernible] please. Sorry, Kelly.

I have a sort of 2-part question on MCED. The first is just want to make sure I'm understanding how this is going to be actually play out. So if somebody comes in, they're getting a Shield test for colorectal cancer, they're a Medicare patient, it's reimbursed. Your assumption is that as long as the doctor has also ordered the multi-cancer test and the patient has done the authorization that you asked for, then you can provide the multi-cancer result without charging separately for that. It will just be incorporated into -- you'll still be able to charge the Medicare fee and provide the multi-cancer result.

So actually, it's pretty simple, right? It's the same test. It's a single test. It's not 2 tests. It's just a single test. And then when the patients are getting tested for Shield CRC, doctors can have the option of opting in for this MCED findings. And as long as the patient is willing to give -- sign a form of authorization of release of medical record, there's an exchange of value and actually then we would release the MCED findings to them. We wanted to be very thoughtful about this, and we decided to pilot it in a few accounts just to see, is there something we're missing? It sounds kind of very obvious, very straightforward, very simple pathway.

And the feedback we got from physicians and patients has been very overwhelmingly positive. So we say, okay, it looks like it's working and let's go and scale it up at broad scale.

The exchange of value is sort of what allows you to...

And like we are doing actually the data collection for our clinical trial for MCED trial, right? So we need that data in terms of generating the evidence for this breakthrough device. And I think it's a huge value that we need to get in terms of evidence generation and potential value for patient and physician. And we see we are excited to put it out there and see at the broad scale, what would be the reception of patients to participate in that data collection initiative that we are talking about.

Sure. And then the second follow-up on it is, I mean, obviously, we're seeing some real success with Grail out there. Will this only be available if you're going in and getting a colorectal cancer screening test? Or are you going to make the MCED test available to -- in some other way to people who would maybe pay out of pocket, but want to be screened for multiple cancers?

So step by step, like step by step. Right now, actually, we are thinking to just add this MCED findings based on the pathway I mentioned to the patients who are getting tested for Shield that we have in the marketplace today. And then we evaluate like we have this kind of really belief at Guardant that we are doing all this hard work, building breakthrough innovative technologies. We want to make sure people get broaden access to this kind of innovative technologies versus just maybe a pathway that would be suitable for the most affluent people who can't pay such a big out-of-pay costs.

I'm impressed and very pleased that our peers and other companies have built that market for affluent. I give them a good kudos. But we wanted to make sure we really democratize that and make sure that people can have the right level of access to that test if they want to participate and if the physician is open to get that information. So that's the pathway that we are pursuing.

Random number generator says Dan Brennan.

Dan Brennan from TD Cowen. Maybe one for Mike and then one for Helmy. So Mike, the 65% to 70% gross margin target for 2028, did you talk about what that translates into, excuse me, for operating margins? I know you talked about cash flow. I just be interested in that. I know the last target, obviously, 2 years ago, you set out to 2028. So I'm just wondering, even if we look beyond '28, kind of how does operating leverage unfold for the business?

And then, b, just maybe a multipart just on MRD, just you threw a lot of information at us. So the Ultra kind of when will we get an update on that? Any color, any early data? The PEGASUS deescalation reported at ESMO, I know you've reported out some data on this already, but how important could that be? And then monitoring, you spent a lot of time on monitoring or MRD. So I'm just wondering where that really fits in because it's not very clean versus the MRD players.

Yes, I'll start. No, I mean, we didn't talk about operating margins. We're focusing on gross margins. We know we can improve those across all of the products. And then we're focusing really on getting to cash flow breakeven. So we're really pleased we brought that forward. I think from an operating margins and then getting positive, obviously, once we start to generate positive cash flow, we're probably in the area of getting positive operating margins.

And so yes, looking forward beyond '28, I think we would then expect to be generating positive operating margins. But I think our focus at the moment, we're absolutely laser-focused on getting to this breakeven point and then starting to get into cash flow positive territory. So maybe at the next Investor Day, we'll talk about operating margins, and we'll look further out in 2028.

I guess maybe I'll let Craig talk about PEGASUS in terms of the importance of that, and then I'll take the other 2.

Yes. So PEGASUS, of course, is a utility study. And so using a tissue-free MRD basically allows a decision about follow-on therapy. And so this is really the first time that we're going to show that utility decision and the impact that has. Obviously, we're all hoping that, that creates a benefit, in other words, deescalating those that don't need it and those that do. And the results we'll be seeing in October basically next month. So very important study as we move from measuring the device to actually now the device changing therapy.

Yes. In terms of Reveal Ultra, we're really excited about kind of what we're seeing in terms of early data from that platform. We're seeing, obviously, in major cancer types, lung, breast, colorectal, really good performance in terms of limits of detection, ability to really detect things at levels that really are sort of beyond kind of what has been in the published literature right now.

And it's kind of a really cool way of how we use our platform, both the genomics and epigenomics and so on to be able to get to such low levels of disease. And, yes, obviously, we're keeping some things close to the chest right now, but we'll obviously release more data as time goes on. But it's something that we think -- the other piece about it that I think is exciting is that it really works synergistically with 360 Liquid with tissue and so on. So it's really a nice puzzle piece that fits in with all our other tests in the portfolio. It's not just something that's shoehorned in like you see in some portfolios.

And so we think it's really going to sort of create a really kind of a nice platform for physicians basically in terms of any scenario, any cancer type rare cancers that may not shed very much, you'll be able to see this, I think, with very high sensitivity and very high specificity. And nice thing about a lot of our cohorts is that we've talked about we have tissue for a lot of these things, so we can develop clinical data very, very quickly.

In terms of monitoring for Reveal for therapy selection, IO has been something that we've had, other companies have had in the therapy selection space. But IO is only one small segment. It's a large segment, but still not the majority of how patients are monitored when you think about successive lines of therapy in terms of first line, second line and so on. Now obviously, our vision for liquid biopsy since day 1 has been this idea of adaptively managing disease over time. And to do that, you have to take measurement points across essentially disease ebbs and flows. And to do that, you have to be able to monitor really all classes of therapies.

And chemo has been one that has frankly been challenging, I think, for ctDNA monitoring. There's some effects that can happen on chemotherapy and so on, a lot of tissue that can be released, collateral damage and so on. And the fact that we've now validated the platform for chemo, I think, is really exciting. And it really, I think, is a major step towards this vision of essentially really becoming a surrogate or this kind of liquid scan to the sort of CT scans that are used as table stakes in the space right now.

And so to be able to go in and say, use Guardant360 here and Reveal in the intervening periods and then switch back to 360, and the fact that we can do that without sending another sample and when you reflex from one to another, I think really gives us a competitive advantage in terms of how these products work together. And so that's why I might have spent a lot of time on that because we think it's something that's going to catalyze further adoption in the therapy selection space as we bring Reveal into therapy selection for monitoring.

Let's see what Dan Leonard has up his sleeve and then Jack and Danny Brennan, you just turned yourself to do merits for the 7-part question.

All right. Thanks, Eric. Nothing up my sleeve, I promise. Helmy, I have a question about SERENA-6. You talked about that multiple times. Can you give us a flavor of what the pipeline of SERENA-6 like trials looks like in the biopharma landscape? And then also, how do you balance your enthusiasm for that trial and that application with trials like SERENA-4, and even Roche on Monday had data from their SERD that could be used in all comers.

I don't know, Jaime, do you want to.

Yes. Maybe I'll start. I mean I think there was a lot of enthusiasm and excitement with our biopharma customers after the readout at ASCO. And so I think that's been a catalyst for more conversations about innovative trial designs that would enable surveillance like approaches. But I think we have nothing really to announce at this point. I think those conversations and opportunities are progressing. And so we think it will be a great catalyst, though, for more opportunities like that in the future.

Yes. I would say like there are a lot of other trials where anything where there's a resistance mutation that is emerging in a population, which is basically almost all targeted therapies have that sort of phenomenon. So things like prostate cancer with androgen receptor like resistance, there are similar trials that are shaping up there. So this is not an isolated sort of incidence in terms of breast cancer and this type of monitoring.

I have no doubt that this is going to be the future of all of cancer care, being able to monitor patients, switch therapies aggressively once you see molecular progression there in that patient population. In terms of like the -- whether it goes to all comers or not, that's the risk with every trial and every drug. But we know that there are patients that don't respond to these therapies. And so right now, ESR1 may be an imprecise sort of tool when we think about genomics. And we know that there are more precise tools like with our Smart platform and epigenomics actually seeing those patients in either population that respond or not.

So I think that may be a stop in the way, whether SERENA-4 reads out and is positive or negative, but it doesn't change the underlying biology that there are patients that respond and patients that don't respond to drugs. And those that respond will eventually form resistance mutations and will unfortunately need monitoring in a successive line of therapy. And so I always bet on biology and where it's going. And we have no doubt whether it takes 1 year, 2 years, 3 years that's where space is headed.

I wanted to add another MRD part to Dan's question, which is maybe for Mike, within the 2028 target, how much revenue is embedded for MRD sales? And maybe for Helmy, as you look out, you introduced Reveal Ultra. What do you think the mix looks like between tumor-informed versus tissue free? Do you think one is going to be larger than the other when we get out there?

Yes. Well, I can start then. Of course, we're not breaking out within the oncology, the different revenue lines. But I think it's fair to say with all the opportunity that we talked about with Reveal, the expansion to other indications with therapy monitoring with Reveal Ultra, we do -- we envisage that by 2028, it's going to be a material part of our overall revenue without putting a specific number.

So we feel -- it's -- I think some other thing, it's our fastest-growing oncology product from a volume perspective. We think that's going to continue. So again, as a proportion of the oncology revenue, that's -- it's going to increase over the next 3 years. So hopefully, that answers without giving some specifics. But it's going to be a big driver for us to have this 30% CAGR over the next 3 years for oncology.

Yes. I would maybe sort of answer that question by pointing to therapy selection in some ways where tissue until now has been the majority of the market. And there's no doubt in my mind over the next 5 to 10 years, liquid will be the majority as patients are tested multiple times as you get to patients that are not as accessible and sort of easily tested with tissue.

And I think the same phenomenon will happen on the MRD side, where certainly now tumor-informed, tissue informed is the majority of the market. But we see tissue-free eventually becoming really probably the biggest part of the market if we fast forward 10 years from now. That being said, we're excited about both products. And I think there's some exciting features of the product we have that will allow us to answer that question more clearly once we launch it.

Let's try Casey from JPMorgan.

Can you just elaborate on the USPSTF pushout? What's the new time line for Shield data generation and ultimately submission for USPSTF? And then any sort of color on the data you plan to share with them? And then just as a follow-up also, you mentioned that you're seeing strong traction from Medicare Advantage payers for Shield even without USPSTF. So can you just elaborate on what's driving payment there?

So in terms of data generation for USPSTF, we have everything you need it. We don't -- we are not waiting for any other study, any additional evidence. We have multiple papers, multiple studies, a couple of randomized studies, our NEJM paper, FDA, we have more than historically was needed for guideline inclusion. But they have to start the process and start reviewing the evidence for it. And maybe I'd use this opportunity, and I introduce you guys to our Senior Vice President of Public Affairs, and maybe she can share with you some of the latest that we are hearing on task force and some of the activities there that could be interesting.

Jen Higgins, nice to talk to you guys. A couple of positive things about the task force is that over the past 5 years, we've worked really actively in Washington to kind of figure out what's happening with colorectal cancer. Obviously, tremendous advancements in the space, not just from Guardant, but from other companies. And I think one of the positive things for us has been the fact that we aren't the only ones wondering where the CRC recommendation is, which is a positive.

About 60,000 patients across the country as well as numerous stakeholder groups out in and outside of the CRC community have not only encouraged the last administration, but this administration to take a closer look and move faster to at least move forward with the recommendation. Now that's no guarantee, but at least it shows the strong momentum to see and break this loose. We know how important this is in terms of the context of how it's tied to timing for a lot of different factors for our business and others.

And so one of the things that we are looking at is making sure that we're doing 2 things: one, working closely on a strategy to engage around quality metrics because we know that there is momentum and the likelihood of a delay for the task force. We have the ability to engage to say what are other guideline bodies that NCQA and NCMS could work together to evaluate around. So benchmarking to USPSTF is difficult if USPSTF has not yet taken action. So the potential for something like ACS or NCCN guidelines to be a reference point for quality metrics, we believe is a potential catalyst for this in the absence of a recommendation from the task force.

I think the second point, too, is that from our standpoint, on a government affairs front, a lot of the work that you've seen Guardant and other companies do with respect to state legislative efforts is important as we anticipate ACS guideline inclusion. There are 10 states where we can move forward quickly in those states. But if you look beyond that, there are a number of other states that have coverage mandates for CRC screening that are linked to USPSTF or frankly not linked to anything at all specific to guidelines.

We've worked actively in a few states like Florida and Louisiana to move the process forward to expand those guideline recommendations to include not only USPSTF, but also ACS and NCCN, right? So there's a positive momentum there.

And then I think finally, on the task force, there are a number of states that are linked to the task force that we could also tie back to legislation and link them to ACS. So we have a strategy to employ to help to expand the number of states where we would have potential coverage in 2026 and 2027 as well as an effort to recognize that the delay in the task force does not inhibit our ability to move forward with that quality metric strategy. In fact, it probably creates a catalyst for faster action from NCQA and CMS.

But time line, again, cannot control the U.S. government, but we are having great dialogue with this administration about the importance of CRC and moving forward on that recommendation as quickly as possible to support innovation as well as patient access.

So exciting signals, but we are not counting on any of that. So just to set.

And I was going to say Jen is really kind of a secret weapon of ours in this space. So I look forward to you guys maybe spending some time with her at lunch.

Thank you guys for putting this data together. You -- Craig, you have an enriched database for cancer signatures. How do you go about figuring out epigenetic signatures for other diseases as you think about expanding into beyond cancer?

Yes. So one of the things we think about, obviously, is the unmet medical need first up to making sure that there's an area we need to define a patient population. And if you think about it, different diseases have expression of protein, which is expression of the epigenome. And so by identifying where there's differences we can actually pick them, we can look through our database to see if there's epigenetic signatures that are different or epigenetic expression is different. And that links then to that outcome and that unmet medical need that we talk about. So that's sort of how we start from the top end to come down.

Got it. And AmirAli, some of the MCDs are annual like lung cancers and breast cancers, probably a 3-year time line isn't suitable for them. So as you think about self-pay annual MCDs that are available in the market today, how do you see Shield with MCD option play out? Have you heard any feedback from physicians on those testing frequency?

I think over time, when you want to think about it very long term, as I mentioned, very envisioning, a blood test that would be used for annual checkoff for multi-cancer detection and even potentially multi-disease detection. But we have to go at it step by step, especially for us that we want to go after vast majority of this market, regular people that if out of pay pocket is like just more than nominal, they cannot utilize those services versus most affluent patients.

So for that one, we have to go step-by-step, generate evidence, maybe get regulatory approval for other indications. That's why our lung cancer screening indication, we are excited about it, and it would be a strategic indication for us for Shield. So we have a pathway for it, but it's going to take a few years. And -- but right now, this is what we can offer to a patient. I think it's going to be great potential for us to build that database, clinical evidence for potential submission to even agency with that data and for a patient to get access to that data on a trial annual basis, step by step.

Let's do rapid firing. Andrew Cooper, Ray J, Kyle and Mason.

Perfect. Maybe first, just, Mike, for you. Glad to see the free cash flow pulled forward. It sounds like you kind of specifically called out some inflection in Shield there in '27 and into '28. But previously, you had tied the ramp in the sales force to USPSTF time line. So just, is that a little bit decoupled now? Are you still ramping at the same pace? Or has there been any change to the plan there?

I mean we're still ramping at a relatively same pace. I think last Investor Day, when we assumed those guidelines were coming earlier, we gave a similar number of sales reps by 2028, the 600 to 700. So yes, I mean, the pace will continue at a similar level. And again, the Medicare population, the over 65, it's a huge field for us to mine, and we've been very, very successful. So I think, yes, that ramp is going to continue similar to what we've previously assumed.

And maybe add a couple of additional statements. So as Mike mentioned, this pricing of ADLT, we didn't imagine before. COGS of Shield is reducing faster than our original expectations. So we are generating more gross profit. And something which is very fantastically happening on the commercial, which was way more than what I thought, is this targeting is really working, like the payer mix has been shifted very dramatically toward the reimbursable cases. So when we are reinvesting that gross profit, like by end of this year, more than $250 million, we thought maybe we're going to be $150 million by end of this year. Just imagine, we are not talking about next year, but just imagine how many sales reps we can have by end of next year. It's very exciting.

And then one quick follow-up just on MRD, following on to, I think when Jack asked. What have you seen from the marketplace that makes you feel like Ultra is the right product at the right time? It sounds like the true ultra sensitive is really what you were highlighting. Just would love kind of the thoughts on how that fits into the landscape with what everybody else has talked about.

Yes. No, it was -- I was at ASCO this year, and you can hear many of the talks. We're talking about some of these tests are just not sensitive enough, need things that are more sensitive, that are get to this sort of ultra-sensitive level of MRD detection, especially in rare cancers, certain metastases, potentially don't shed as much and especially in some of those like think about deescalation studies where you really want to make sure that you can spare the patient from chemotherapy.

And so we saw that I think that maybe there wasn't as much progress as we expected maybe in the field in terms of tumor informed and sensitivity. And obviously, we have a lot of research we're doing inside the company, and we saw there was a potential, I think, unmet need that we could address with this sort of ultrasensitive approach. I mean these technologies that only look at tens or hundreds or even a couple of thousand mutations are not probably where the sensitivity needs to be to be able to get to the levels we're talking about with our technology.

Kyle Mikson from Canaccord Genuity. Just on NSAID, so just clarify merely how many cancers you'll be adding? Is it just lung, for example? What's the time line and the pathway, let's say, to FDA submission and approval? And then if these other tests get reimbursement for $500, like that's in the kind of ongoing legislation, how could this test at that higher price -- much higher price point compete?

Yes. So right now, actually, we are targeting 10 cancers, between 10 cancers, like one of them is breast, the other one is prostate that -- it's kind of performance, these are low shedder stuff. So that's why we are highlighting the 8 other cancer type into our performance, but it's a panel of 10 cancers right now. In terms of that legislation, actually, it's pretty interesting. It would be, I think, a tiny positive for us, but there is so much limitation with it like price capping in some aspects of it.

But like we see what's the latest is going to be, but the latest I heard from the team is now maybe it's just going to be for patients at age 65 and just 65. And then every year, it's going to go up, or 68 and just 68, I forgot which one. But effectively, it's going to take 10 years to even have a coverage of 65 to 75, right? So versus the pathway that we have enables us potential access for patients much, much faster and as a result, much bigger opportunity.

In terms of FDA submission, we need to see really in real world what fraction of the patients would participate in this kind of clinical data generation initiative. We are expecting to generate data from a few hundred thousand patients. And once we have that, I think we are sitting on a statistically powered study to align with the FDA to review that evidence. I don't know, Craig, if you want to add anything.

No, no, that's...

Perfect. And then just a quick one on the push into the $300 billion multi-disease screening market. Is that totally going to be organic using, I guess, like if there's any AI? Or is that going to be -- are you open to acquisition, let's say, as well?

Sorry, I missed the question. What's the?

Do we do it organically or we acquire companies or technologies?

Again, we'll be exploring both options as we move forward. But at the moment, the focus is organically is where we're focused.

But yes, I think that's the underappreciated aspect though of what we've built here is that it's an architecture because it's blood allows us to go well beyond just cancer. I mean I think when you think about genomics, it was really confined to rare disease, infectious disease and cancer because that actually changes the genome.

But almost every disease impacts the epigenome. And so this chemistry allows us to transform this huge blood biobank we have and this sort of data acquisition through blood that we have as a company into a vehicle that allows us to essentially rinse and repeat the same process we did for cancer for every other disease potentially that we can see. And we're seeing really exciting signals, I would say, for many other diseases, inflammatory diseases and liver diseases and so on. And so we think that it's underappreciated in terms of like where we can go versus, let's say, a tissue company or a stool company or something. It's very hard to go into multiple diseases when you have -- you're limited by the specimen collection that you have.

I can add, I mean, at the end of the day, you think about a disease like rheumatoid arthritis. Two rheumatoid arthritis patients have different outcomes to their treatment. They have different response to disease. The disease can be worse for some 1 week, not for another, plateaus, stable. That's all epigenetics. Everything that happens in that patient -- that's why I'm saying you start with the clinical piece, and with the data we're building through our Shield and collection through screening, we have to screen rheumatoid patients.

So what we've got to do now is say, okay, these rheumatoid patients respond once to therapy is stable. These rheumatoid patients respond and 3 weeks later, they're relapsing and don't respond to therapy. That's epigenetics. So you just start to look in the epigenetics and you can start to pick these patients out. And that's what we want to achieve with cancer as well. We want to pick out the patients who respond to therapy and those that don't respond to therapy, substitute rheumatoid, substitute Crohn's disease, et cetera, et cetera. So the model is the same. And epigenetics is -- whatever you see can be explained through epigenetics. We just don't know what it is at the moment until we get the data basically.

Let's try Mason and then Brandon.

Maybe on the MRD opportunity, specifically, those 12 million patients that are 5 years out plus or 5-plus years out from surgery. Could you just talk about like your access to them today? How -- what proportion of them are still routinely seeing their oncologists? What has to happen to really unlock utilization there?

I mean I think it depends on the tumor type, how often the follow-up is going to be. And I think that we've -- that's something where patient activation is probably going to be part of the commercial strategy because to your point, if a patient is not going into the office, then the testing isn't going to take place. And I think to AmirAli's comment earlier, as more entrants come into any given market, and in this case, MRD, it elevates the collective voice around that new technology.

At this point, I think Helmy showed it's less than 3% of the collective market is penetrated, which suggests a combination of low awareness, obviously, data generation, which we're working on and to some extent, which we're looking to solve with Ultra that the current solutions don't deliver what the market needs. But as those forces, I think, come to bear and as the MRD market matures, that in and of itself is going to lead to additional patient awareness, which over time is going to activate that prevalent population.

I'll just add that we have programs with many advocacy groups in terms of survivorship campaigns and so on where we can sort of activate them. And then obviously, over time, the primary care channel is going to be a very important avenue for us to be able to essentially get to those survivors that are further out. And so that's why I think it's really important when you think about the overall MRD opportunity, especially at scale that, frankly, you have a primary care channel and sales force to be able to access all of it.

Last question, Brandon, please.

Brandon at Wells. Two questions on Shield. The free cash flow breakeven range of $600 million to $800 million, it's a pretty wide range. What are the variables there? What are you leading cushion for? And if you're doing $500 million with 700 reps, truly, that's not the endpoint. So how do you think about rep productivity long term? Could it approach the incumbent over time?

I think the main driver between -- of that range, and we think that's a good range. It's going to be the ASP and just a little bit of the -- we talked about before, the mix between Medicare and Medicare Advantage and how quickly we can ramp up the commercial reimbursement. And so it's going to depend on that mix because that's going to have a little impact on our overall gross margins. But I think from the OpEx side, we know what we'll spend on our research and development. It's going to be relatively flat over the next few years. And we've laid out our plan to expand on the field sales team. So yes, the main variable that's going to drive that is ASP and the gross margin. Did you want to?

Yes. In terms of opportunity per rep, this is still even at that $500 million, like we talked about, is just 2% market penetration in this unscreened patient population. And at that level, we are going to have like the right breadth of commercial infrastructure in place. So we don't need to like significantly increase from that point. It's just going to be over time, the reps would become more and more productive.

We are seeing something pretty interesting in the accounts which are tenured -- for the reps that are tenured, even today, higher depth of ordering of Shield in those accounts is giving us some very interesting revenue per rep in those accounts, which when you just kind of extrapolate, you get to some kind of very crazy number. So it's just -- we are 1 year into it. We have to see how this thing would kind of evolve over time. And -- but definitely, $500 million is still is just, again, less than 2% market penetration.

And with each guideline inclusion, the rep performance will get stronger and stronger.

That's right.

On that note, stop of the hour. Thank you, guys, for coming out.

Thank you.

Okay. Great. I think we can get started, everyone. Kallum Titchmarsh here from the Life Sciences team at Morgan Stanley. Really pleased today to be joined by Helmy Eltoukhy, Chairman, Co-Founder and Co-CEO; AmirAli Talasaz, Co-Founder and Co-CEO; and we have Mike Bell, CFO as well with us. So before we get started, I have to read you some disclosures.

So please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. So maybe let's start off kind of high level, Helmy. It's now 13 years post founding. Each year, obviously brings a lot of new stuff to discuss. So maybe just reflect on how you feel the company has progressed over this time and whether where we sit today aligns with your mission back in 2012.

Yes. Look, when we started the company, we had a crazy idea of having a blood test at an annual physical that could sort of keep cancer at bay and detect it early. And we wanted to do that systematically by launching tests in therapy selection, MRD and screening. And here we are 13 years later with the first company that has Medicare reimbursed products across all 3 areas of patient care. So it's -- on the one hand, it was part of the plan. But on the other hand, looking back, it's pretty amazing that we actually set out to do it and accomplished that now.