NTRA - NASDAQ

Hello. Welcome to Natera's 2025 Second Quarter Financial Results Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded today, August 7, 2025. I would now like to turn the conference call over to Michael Brophy, Chief Financial Officer. Please go ahead.

Thanks, operator. Good afternoon. Thank you for joining our conference call to discuss the results of our second quarter of 2025. On the line, I'm joined by Steve Chapman, our CEO; Solomon Moshkevich, President, Clinical Diagnostics; and Alex Aleshin, General Manager of Oncology and our Chief Medical Officer. Today's conference call is being broadcast live via webcast. We will be referring to a slide presentation that has been posted to investor.natera.com. A replay of the call will also be posted to our IR site as soon as it's available. Starting on Slide 2. During the course of this conference call, we will make forward-looking statements regarding future events and our anticipated future performance such as our operational and financial outlook and projections, our assumptions for that outlook, market size, partnerships, clinical studies and expected results, opportunities and strategies and expectations for various current and future products, including product capabilities, expected release dates, reimbursement coverage and related effects on our financial and operating results. We caution you that such statements reflect our best judgment based on factors currently known to us and that actual events or results could differ materially. Please refer to the documents we file from time to time with the SEC, including our most recent Form 10-K or 10-Q and the Form 8-K filed with today's press release. Those documents identify important risks and other factors that may cause our actual results to differ materially from those contained in or suggested by the forward-looking statements. Forward-looking statements made during the call are made as of today, August 7, 2025. If this call is replayed or reviewed after today, the information presented during the call may not contain current or accurate information. Natera disclaims any obligation to update or revise any forward-looking statements. We will provide guidance on today's call, but we'll not provide any further guidance or updates on our performance during the quarter unless we do so in a public forum. We will quote a number of numeric or growth changes as we discuss our financial performance. And unless otherwise noted, each such reference represents a year-on-year comparison. And now I'd like to turn the call over to Steve. Steve?

Thanks, Mike. Let's get to the highlights on the next slide. We had a phenomenal quarter. We generated $547 million in revenue, which is 32% growth over Q2 of last year, and ex revenue true-ups, our revenues grew 34% year-on-year. We had a very strong volume quarter as well, which included strong growth across the product portfolio and an all-time record for Signatera. We processed 189,000 oncology tests in the quarter, which represents nearly 20,000 units of growth compared to our first quarter of this year. 20,000 sequential growth units significantly beats our previous growth record and is a new milestone for the company. Part of this growth acceleration was driven by a significant increase in new patient starts, which was double our previous quarterly record. Gross margin ticked up again in Q2 at 63.4% compared to approximately 59% this time last year. Ex true-ups, gross margins were consistent sequentially versus Q1 due to strong ASPs despite the fact that Signatera COGS actually went up meaningfully because we ran so many exomes for first-time patients, which, of course, is very good news. Given all that momentum, we are in a position to level up the financial guide for the year. We are raising the revenue guidance by $80 million at the midpoint, and we now expect revenues in the range of $2.02 billion to $2.1 billion, which is a full reset of the prior revenue range. We are raising the gross margin guide to 61% to 64% in recognition of the gross margin performance we saw in the first half, which still accounts for factors like growth in new patients in the second half. We are not increasing our operating expenses, which are remaining flat versus the prior guide as we get scale in the business despite being the full investment mode for the future. In addition to the financials, we have a full slate of new data and product updates to discuss today. We are particularly excited to launch Fetal Focus, a new NIPT for inherited conditions that leverages our proprietary SNP-based method for NIPT. We've never had better momentum in organ health and the Prospera data that we'll talk about today, I think, shows the path we're on to transforming care for organ transplant patients. In oncology, the data pipeline continues to grow, and we're going to take some time on the call today to do a deeper dive on our strong and broad data across breast cancer and new data in GI cancers beyond CRC. Finally, we've been working in the background on the next major wave of innovation at Natera. First, we'll go over the rapid progress we're making on early cancer detection, where we're gearing up for a big readout of the prospective colonoscopy match PROCEED trial for advanced adenoma late this fall. Next, we will introduce Natera's AI-based foundation models, which are being used to develop new diagnostic biomarkers, molecular therapeutics and speed clinical trials. Okay. Let's get into some of the business trends on the next slide. The first slide just shows our Q2 volume progression over prior years. This was another great quarter for us across the board as we were able to grow significantly against the Q2 2024 comparable that was elevated due to a sudden influx of Invitae units. Signatera was phenomenal with growth records in both sequential growth and new patient starts. In women's health, we saw our second best volume quarter ever coming off what was a blowout Q1 number. We saw the same Q2 seasonality trends that we always see, given our large base of existing customers, but we continue to blunt that impact by winning new accounts. Our organ health products have been on a tear this year with major new account wins driving growth on the back of some very strong clinical data, and there's more new data that we're going to talk about today, which I think sets us up very well for the future in that space. We also recently exited our legacy paternity business, which was contributing to our volume numbers historically. The next slide shows our Signatera clinical units over time. This quarter, we grew by 20,000 growth units versus our average over the prior 4 quarters of about 13,000 per quarter. This overperformance was a result of a wave of new patient starts, driven by the compelling data we generated in the last year. Growth in new patient starts was about 3x higher than our quarterly average and about 2x higher than the previous record quarter. As we said before, Signatera quarterly volumes could fluctuate. So I don't think 20,000 growth units is a new normal, but clearly, this strong growth is a great sign. Historically, a lot of our growth has come from colorectal cancer, breast cancer and IO monitoring. And again, we saw very strong growth in these areas. In addition, we're now seeing broader adoption in many other tumor types as physicians really start to generalize the use of Signatera in their clinics, which is helping drive volume growth, but also creates a large revenue opportunity. We're in the process of seeking Medicare reimbursement for this longer tail of cancers. Based on our current growth trajectory, gaining Medicare coverage for these noncovered histologies over the next few years should be worth approximately $250 million to $300 million in annual revenue and gross profit, further contributing to the financial sustainability of our growth strategy and supporting our path to a $2,000 ASP. We're in an excellent position to achieve this, given the significant amount of data we generated so far. And of course, we have over 100 clinical trials underway, many of which support these types of initiatives. I mentioned we grew revenues 34% organically year-over-year, and you'll recall, Q2 of last year was a very strong quarter for us, so I'm pleased to see the strong growth numbers over some very tough 2024 comparables. We had about $45 million in revenue true-ups this quarter as we continue to improve reimbursement for covered services. Sequentially over Q1, we grew revenues 9% overall and 7% organically. We've already covered the very strong volume levers driving this growth, but we also saw excellent ASPs across the board. The next slide shows our gross margin traction over time, and we posted another strong gross margin quarter in Q2. Stripping out the revenue true-ups, we were still able to generate gross margin steady with Q1 despite the big step-up in exome volumes this quarter. We drove that with better ASPs for Signatera, which is now roughly at $1,175 along with steady results in ASPs in Panorama, Horizon and growth in the Prospera ASP. We were also very pleased to see continued revenue true-ups in the quarter, which means that cash collections exceeded our prior history. I think the speed at which we're converting receivables into cash is one of the most promising business trends we're seeing. And DSOs are now down to 57 days, which is a record for the company by a wide margin. All of these trends allow us to generate cash, while aggressively investing for future growth. Although this slide shows how much progress we made over the last 2 years, I really think we are just scratching the surface of the margin improvements we can achieve. We think about margin expansion opportunities across 4 primary vectors: continued execution of revenue cycle operations; expanded coverage for products, including Signatera; further COGS reductions; and AI-driven efficiencies. First, we embarked on a major investment in our revenue cycle operations, leadership systems and staffing in the fall of 2022, and that project has yielded significant returns for the company. Our team sees ample additional opportunities to continue to make improvements, which could drive ASPs higher, and we've seen good results so far this year. One example is on appeals. Historically, it's very difficult to do an individualized appeal for each denial. But as our systems improve and we invest, we're building these types of capabilities that will allow us to get paid on a higher percent of cases. Second is expanding coverage for our products. We mentioned on the last call that we think $2,000 is an achievable ASP for Signatera. I mentioned the new opportunity in front of us to drive reimbursement in a number of additional tumor types, and I'll stress that this opportunity has gotten much larger over the last couple of quarters as our volumes in noncovered tumor types have grown, and we expect to have several additional coverage decisions within the next 12 months. We continue to see positive early signs in biomarker states, which is still at the very early stages, and we still have opportunity with Medicare Advantage execution. Outside of oncology, we still have major opportunities for improved coverage with expanded carrier screening, 22q and broader coverage for our organ health products, which could all drive ASP improvements. The third area of improvement on margins by cutting COGS. One of the constants for us over the last decade is our commitment to investing in R&D projects that reduce cost of goods sold for new tests that we launch. This tends to have a relatively lower technical risk compared to new product innovation and deliver high returns. We now have a full suite of COGS projects we're initiating and some that are getting close to launch. Finally, we're going to spend some time later on the call on the investments we're making in artificial intelligence. Well, there are some very exciting steps we're taking in AI-fueled innovation, there's a whole range of areas in the business where AI is already having an impact and allowing us to scale our volumes without a one-for-one increase in headcount. Many of these opportunities hit COGS as well as OpEx, and we expect to see some significant savings from this over time. So in summary, we have several very concrete ways that we can increase the margin. Now not all of these are under our direct control and the path won't always be linear, but it's great that we have these opportunities that we're executing across. On the next slide, as I mentioned at the top of the call, we're holding OpEx steady even as we raised top line revenue guidance by $80 million. So we're getting scale even as we keep our foot on the gas with growth investments. We think these growth and margin expansion opportunities clearly warrant the investment required to deliver them, and this slide gives some additional color on where the incremental investments in 2025 are going. To be clear, the vast majority of the OpEx increase in 2025 is not yet driving revenue, either because it's pointed at a longer-term project like gaining reimbursement for uncovered services or completing a major clinical trial or delivering on new product launches or because our commercial hires are just coming on board and are not yet productive. I'll follow up on that example of commercial hires. We've recently expanded our commercial footprint primarily in oncology. We added these additional oncology reps, and we expect to start seeing meaningful contributions from these new people late this year and early next year. As with a lot of these investments, there's a slingshot effect where they're hitting the expense line this year, but they don't start to impact revenue and volume growth until about 6 to 12 months later. The strong growth we've seen thus far this year wasn't really driven by these new hires. In addition to the commercial team, we continue to invest in the success of the revenue cycle management. As we said earlier, investing in revenue cycle management is one of the primary opportunities we have for margin expansion. So this makes a lot of sense to pursue. Once this team has scaled up and the optimal tools and systems are in place, we can get significant scale on top of this infrastructure. We've been moving quickly here, which includes many manual processes that can be automated, so we don't have to keep scaling at the same pace going forward. The forecast also includes a meaningful addition of AI-focused technical staff that we think is very promising. We've also shored up our ability to scale with more lab footprint and additional basic company infrastructure to accommodate our growth. The R&D incremental investment in 2025 is really driven by both the oncology clinical trial expansion and investing into new MRD products. We think this is important because there's so much opportunity in MRD. So we're continuing to expand our already vast set of meaningful clinical trials in effort to change guidelines, accelerate adoption and gain coverage where we don't yet have it. Our pace of new product launches has also increased this year. Earlier this year, we launched Signatera Genome, and we have many other MRD-related opportunities we're working on that will be announced in the future. In addition, we're excited today to have announced another innovation within the prenatal product line with single-gene NIPT. Finally, we're continuing to make rapid progress on early cancer detection, which we now think has the potential to be a major opportunity for Natera. We've executed well on the PROCEED trial, which now has about 3,500 patients enrolled and we intend to read out in late fall. We have also launched the FDA-enabling FIND trial. We think ECD is a very significant opportunity for Natera, especially given the high ASPs that are now being established and the existing distribution footprint we can leverage. Finally, we're investing in AI and AI-enabled technology, which we will outline on the call today, which we think could revolutionize care and make a big impact. We plan to stay nimble on our investment strategy throughout the rest of the year. If we see a clear opportunity to deploy capital, we're going to do that while maintaining our commitment to generating cash later this year. Having said that, I think we're reasonably well positioned to hold OpEx in the current range as we continue to grow. With that, I'm very pleased to hand it over to Solomon. Solomon?

Thanks, Steve. Let's start with the news from women's health, where we had an exciting launch of our new Fetal Focus NIPT for inherited conditions. Let me walk you through some of the background first on the clinical unmet need that we're addressing with this new test, how the test works and the exceptional performance that we're seeing from our clinical validation study called EXPAND. Today, when a pregnant mother is identified as a carrier of a recessive gene like cystic fibrosis, for example, medical guidelines recommend testing the biological father to assess the baby's risk of inheriting the affected gene from both parents. But in some cases, the father is not available for testing. So with the launch of this new test, if a pregnant mother has screened positive on Natera's Horizon carrier screen for 1 of the 5 most commonly tested genes, the Fetal Focus test can directly assess the baby's risk of inheriting the genetic condition just from a maternal blood sample. The test is validated to analyze 5 key genes, as you can see outlined on this slide. And it's backed by data from the EXPAND trial, a large prospective clinical trial that we've been running for nearly 2 years. I want to tell you more about the EXPAND trial. So far, the study has enrolled about 1,300 participants from a diverse multiethnic population, including patients from leading academic centers and MFM clinics as well as a decentralized trial arm that leverages Natera's nationwide base of over 1 million Horizon patients per year. Because of this, Natera is uniquely positioned to enroll quickly into the trial. We see EXPAND as similar to the SMART study in that it's designed to be the definitive trial in this test category with all positive and negative outcomes confirmed by diagnostic genetic testing, either prenatally or after birth. In the first milestone readout of about 100 patients from EXPAND, the Fetal Focus test demonstrated 91% sensitivity to affected pregnancies, where the baby actually inherited the recessive genes from both parents. And the test successfully identified all 5 affected cases with homozygous variants, which are particularly challenging to detect in cell-free DNA. Fetal Focus uses Natera's proprietary LinkedSNP technology, which enhances detection of these challenging cases across diverse ethnic populations. These early results not only highlight the clinical accuracy of Fetal Focus, they underscore the real-world value of Natera's proprietary technology. Together, the product launch and the clinical data strengthened Natera's leadership in women's reproductive health, and it reinforces our commitment to being a trusted partner to OB/GYNs, MFM specialists and patients across the country. Turning now to organ health. This quarter, we announced the publication of the PEDAL study in the American Journal of Transplantation. AJT is the highest impact transplant journal, which speaks to the importance and the rigor behind the study. PEDAL is a first-of-its-kind prospective multicenter trial evaluating how donor-derived cell-free DNA can help predict long-term outcomes after a rejection of a kidney transplant. You can think about this as similar to immunotherapy monitoring in oncology because it answers the question of whether the treatment is working or not after someone has been diagnosed with rejection. The PEDAL study enrolled 488 kidney transplant recipients from 28 participating U.S. and international transplant centers over 4 years. 96 of those patients had biopsy-proven acute rejection and were monitoring with Prospera during treatment every 2 weeks for 8 weeks. And 66 of those patients had clinical outcomes recorded at the 12-month mark. So the findings showed that transplant patients whose donor DNA levels remained high during and after treatment did poorly with 97.5% having negative outcomes at the 12-month mark. By contrast, the patients, where Prospera levels dropped and stayed low, were 60x more likely to experience positive long-term outcomes. This is the first clinical evidence showing that serial monitoring with Prospera can inform patient management during treatment for acute rejection, potentially enabling earlier interventions and more tailored care. We've got an incredible feedback on the data and the study quality. Doctors were really eager for this type of readout. It took a long time to run the trial, and we're very pleased with the results. This new use case for Prospera complements the existing utility in detecting rejection and surveillance. As you know, Medicare has recently released a draft LCD updating its coverage policy for surveillance, which we also believe is positive news. Turning now to oncology. We had several important events for Signatera in the past few months, continuing to fuel the adoption of this amazing technology. At ASCO, we presented interim results from the DARE trial, which has accrued over 400 early-stage breast cancer patients with HR-positive, HER2-negative disease. This trial is what we call a TOMR trial for treatment on molecular recurrence. TOMR has the potential to become the new frontline of metastatic treatment, where the recurrence is detected first by Signatera even though the scans are still negative. The DARE study has been recruiting and randomizing patients since 2021 to either receive CDK4/6 inhibition at time of Signatera positivity versus continuing standard-of-care observation. There are 3 key takeaways from this readout at ASCO. First, patients who test serially negative have extremely good outcomes with over 99% remaining recurrence free. This reflects excellent test sensitivity. Second, the test was so sensitive that 73% of the recurrences detected were purely molecular with the reflex scans showing no evidence of disease. And 93% of those patients were then successfully randomized. So this is a major sign that the TOMR strategy is viable, unlike prior attempts that resulted in lower patient randomization rates. As a reminder, the other 27% of patients in whom disease is detected on a scan, also stand to benefit from early detection and treatment of metastatic disease. Third, we saw a twofold higher ctDNA clearance rate in one of the trial arms, providing a promising signal that early treatment intervention can make a difference at this stage. So we look forward to further readouts from the DARE trial and to doubling down on the TOMR strategy with our partners from biopharma and academia in breast cancer and other cancer types. Turning now to the neoadjuvant setting of breast cancer, where we had several important announcements. Earlier in the quarter, we presented new data from the ISPY-2 trial, which showed again that patients who tested Signatera negative at baseline or at diagnosis had extremely good outcomes after treatment. Natera's multiyear collaboration with the ISPY-2 team has yielded many important insights and peer-reviewed publications, systematically studying hundreds of early-stage breast cancer patients and correlating Signatera dynamics with treatment response and long-term outcomes. So this insight about the great prognosis when the baseline sample is negative has triggered many doctors to ask whether those patients might safely avoid chemotherapy. And perhaps they can be treated just with endocrine therapy instead, which is much less toxic. So this approach is now being formally investigated in a new clinical trial led by ABCSG, which is the Austrian Breast and Colorectal Study group. The trial is called TEODOR, and it randomizes patients who were Signatera negative at baseline to just receive endocrine therapy versus chemotherapy prior to surgery. The trial is open at 15 sites in Austria and it aims to recruit 250 patients. This is a great example of how strong biobank data generated over many years can lead to a randomized clinical trial that ultimately has a chance to be practice changing. Our plan is to replicate this strategy as much as possible. We've built up a significant clinical pipeline in breast cancer, which we believe is hard to replicate. To date, we have 18 peer-reviewed publications and by our count, presented over 60 abstracts at top medical meetings. We have broad Medicare coverage across the neoadjuvant, adjuvant and surveillance settings. All of this sets the foundation for the next wave of randomized trials, many of which are currently underway and others still to be announced. To ultimately solidify Signatera and ctDNA monitoring as the new standard of care across all settings of this disease, we've invested heavily into the data generation strategy in breast cancer, having spent and budgeted over $150 million on breast trails alone. This is going to be hard for others to replicate given the extent of the capital investment required. Now turning to gastrointestinal cancers. The adoption of Signatera has obviously been strong, especially in colorectal cancer, but it's now growing quickly in other GI malignancies, including pancreatic, liver and gastroesophageal. We had 2 strong peer-reviewed publications in GI over the past 3 months. In gastroesophageal, the PLAGAST study was published in Nature Communications, validating Signatera in the neoadjuvant and adjuvant settings. This study followed 62 patients with locally advanced gastric and GE junction cancers and showed that patients who failed to clear their ctDNA during neoadjuvant therapy had very poor outcomes. Study concluded that those patients would likely benefit from a change in therapy after surgery instead of just continuing the same treatment, which is a common strategy today with perioperative chemo or immunotherapy. Signatera also detected recurrence with a median lead time of 6 months ahead of imaging. Gastroesophageal cancer is a deadly disease with no good biomarkers, where Signatera has the potential to really improve patient management and outcomes. In liver cancer, also known as hepatocellular carcinoma, or HCC, we published a great paper in JCO Precision Oncology that followed 125 patients. Early-stage liver cancer can be treated with either surgical resection or with a liver transplant. And this study saw about half and half contribution. And contrary to esophageal cancer, there is a guideline recommended biomarker called AFP, or alpha-fetoprotein, that simply does not work very well. So in this study, we showed that Signatera significantly outperformed AFP in detecting recurrence with approximately 2x longitudinal sensitivity and 100% longitudinal specificity and with diagnostic lead times of up to 16.5 months. So we're getting positive feedback about this study and growing interest to use Signatera for recurrence monitoring in both resected and transplanted patients. Finally, looking forward, Q3 will be another important quarter for Signatera as we expect data readouts from the IMvigor011 trial in bladder cancer and other studies. Now I'd like to turn it over to Alex to discuss our road map in early cancer detection and some of the exciting foundation models that we're building to fuel the next wave of AI-based innovation. Alex?

Thanks, Solomon. We continue to make steady progress on our ECD program. We have now consented over 3,500 patients for our PROCEED-CRC study, which is a prospective average-risk coloscopy-matched trial. This study is being conducted in a manner to closely mirror our FDA-enabling FIND study to minimize the risk of performance degradation. We plan for the next readout from the study in the second half of 2025, which will assess assay performance in over 100 advanced adenoma samples and 500 normal controls. Additionally, we're excited to announce that the FIND study has now started enrollment and is on track to prospectively accrue the necessary patients to enable our FDA readout in 2027. We continue to phase-gate the program and remain disciplined in our investment. We want to highlight that our investment in our ECD program is already baked in into our operating expenses. On the next slide, I want to highlight one of the most exciting areas this quarter as we continue our investment in our AI initiative, which we're deploying across the entire company to scale our operations, improve user experience, and drive scientific innovation. On the operations side, for the entire history of the company, many roles have had to scale linearly with commercial volume. For the first time, we have an opportunity to change that relationship, with AI allowing us to scale more efficiently and open up additional operating leverage worth approximately $200 million in savings over time. On the U.S. side, we're also building a whole new suite of AI-enabled user experience tools, which are intended to change the way we interact with physicians and patients. Finally, we are leveraging AI to develop new algorithms that will power the next generation of diagnostics and clinical insights. On this front, today, we're announcing our AI-based discovery, the care platform that is designed to support various stages of therapeutic development from early target discovery to clinical decision support. This consists of 3 components. The first is the genomic and clinical data foundation layer on which our models are trained. The second is the core model layer that powers discovery. And the third is the application layer that supports clinical decision-making as well as providing genomic insights. The foundation for this effort is built on a rapidly growing set of de-identified data from over 250,000 patients and over 1 million longitudinal time points, along with abstracted clinical data and information on drug treatment and outcomes. Taken together, this comprises one of the largest multimodal longitudinal oncology datasets that has ever been created with over 1 billion parameters. Utilizing this dataset, we train a multimodal foundational model on our de-identified Signatera and Altera data to power our core AI platform. This supports several key use cases. The first, Natera can create digital twins that can virtually simulate patients for treatment optimization as well as outcome prediction. This can help make therapy recommendations such as suggesting the next line of therapy and opportunities for treatment deescalation. It can also better predict outcomes and can run virtual in silico clinical trials in order to optimize study design and reduce clinical development risk. One recent pilot demonstrated that our algorithm can accurately recommend immune therapy based on real-world EHR data, while another pilot show that it outperformed both TMB and stand-alone pathology-based metrics and predicting immunotherapy response. Next, Natera's real-time clinical trial matching software leverages molecular and clinical data to improve patients and researchers' ability to match individuals to appropriate clinical trials. This capability uses LLMs to interpret eligibility criteria and in structured clinical records, which holds the potential to improve enrollment efficiency, reduce screen failures and accelerate trial time lines. Finally, Natera has developed an immune therapy response prediction algorithm and a molecular therapeutics design model, which we'll review on the next slide. NeoPredict and NeoSelect are the first of many algorithms that Natera has developed to predict immune therapy response and identify potential neoantigenic mutations, respectively. This historically has been one of the most challenging computational problems. And Natera developed these algorithms by utilizing our foundational genomic large language model trained on our longitudinal genomic dataset and has allowed us to demonstrate market leadership in this space. The Tumor Neoantigen Selection Alliance, or the TESLA, database is a reference dataset for benchmarking neoantigen prediction tools. We ran our NeoSelect algorithm against the TESLA database and our algorithm outperformed 25 established models and beat the second place model by around a factor of 2 when identifying highly prioritized neoantigens. While we continue to optimize our prediction and selection algorithms, we believe that these capabilities have very exciting potential in many areas that could improve patient care. We look forward to providing future updates on this program at both academic conferences and in publications. Additionally, Natera has created the NeoPredict algorithm to identify patients or likely either responsive or resistant to immune therapy treatment. NeoPredict leverages the neoantigen prediction capabilities we just described to identify patients who are most likely to benefit from immune therapy. Shown on the right of the slide, NeoPredict significantly outperformed tumor mutational burden in Natera's perspective, BESPOKE IO clinical study. There has been increasing interest in these capabilities from KOLs, hospital systems and pharma companies, and we look forward to providing additional updates in the future. Now let me hand it over to Mike to cover the financials. Mike?

Great. Thanks, Alex. The next page is just a summary of the financials compared to last year. We've already spent a lot of time on the revenue and OpEx trends, so I won't repeat those. A couple of the stats that stand out to me are: first, the top line revenue growth over Q2 last year, where we had the big influx from the Invitae acquisition, as Steve mentioned. I was pleased to see us grow very rapidly over and above that very tough comp from last year. Second, the major ramp we've seen in gross margin jumps out. That's driven by the ASP progress we've delivered over the last year. Steve talked about several near-term drivers to ASPs, and I'm cautiously optimistic that we'll be able to make more progress in the second half, particularly related to Signatera ASPs. For example, we had previously set a goal to get some ASP traction from biomarker states by Q3 2025. And I'm pleased to see some notable progress on specific payers in several states. So I feel confident that our Signatera accrual in Q3 will have some biomarker state benefit. On the quarterly trajectory of gross margins, I'm very happy to see some COGS headwinds in Signatera when that is driven by an influx of first-time patients, which is what we saw in Q2, as Steve described. Finally, I was pleased to see us continue to generate cash even as we double down on the growth investments Steve described for this year. Obviously, that's driven by the revenues and the margins, but also the rapid improvements in the cash conversion dynamics that we talked about earlier in the call. This is really part of the revenue cycle operations that improved ASP, but also allow us to get reimbursed for coverage services in a much more timely manner by optimizing the initial claim submission to payers with all the documentation they need to pay the claim on the first pass. As you can see from the bottom row, we've added approximately $47 million in cash from operations to the balance sheet this year and remain extremely well capitalized with a clean balance sheet. One other comment on the bottom line. We took an accrual of approximately $30 million in noncash stock-based comp and legal expense accruals in the quarter, which I view as nonrecurring. Without that charge, we estimate EPS loss per share would have been roughly $0.53 instead of the $0.74 we showed in the press release. Okay. Let's get to the guide update on the next slide. We are completely resetting the revenue guide to a new range, as Steve described, now ranging from $2.02 billion to $2.1 billion on the strength of the revenues and the volumes we've seen so far this year. The gross margin, we are bumping the bottom end of the range 100 basis points to account for the good results we've generated so far this year. This guide implies that ASP trends will continue to improve while also building in expectations for continued increased adoption in first-time Signatera patients through the rest of the year. So the net impact of those drivers should be that organic gross margin will continue to pick up modestly in the second half. For both revenues and gross margins, I will stress that we do not include revenue true-ups in the guide because they can be lumpy and challenging to forecast. I do expect some true-up revenue through the course of the year as the most recent reimbursement trends have been outpacing our historical results as you see here in Q2. On both the SG&A and R&D lines, we're holding that guide flat to the guide we set in May. I'll just reiterate the point that Steve made on the slingshot effect with respect to these investments. Very little of the 2025 growth in OpEx is driving revenues this year, but we do expect those to drive growth in 2026 and beyond. We are going to remain opportunistic as it relates to OpEx. If we see a chance to fund an important clinical trial or expand a territory beyond the current plan, we're going to do that because we are seeing such steady returns come in reliably on these investments. Finally, just reiterating our cash guide to be cash flow positive this year. The cash flows can be very lumpy, and it's certainly possible for variables like DSOs to bounce around, but our first half performance puts us in great position for the full year. And I'm biased toward the business generating cash again in the second half year 2025. Okay. With that, let me open it up to questions. Operator?

[Operator Instructions] Your first question comes from Daniel Brennan with TD Cowen.

Obviously, congrats on the quarter. Maybe just starting off with Signatera volumes given the 20,000 sequential, and it was a record. Maybe you can just give us some more color on kind of what drove it. Could you speak a little bit about maybe like existing docs and new docs? I think you talked about new patient starts versus maybe surveillance. I know, Steve, you also talked about new indications. So maybe you could just kind of give us some more flavor what drove it? And I guess the question would be, I know you want to keep things conservative, but is it unrealistic to think something in the high teens to 20% could continue?

Yes. Thanks, Dan. So I'd say, first, if you look at the broad amount of data that we've been putting out over the last year and particularly the beginning part of this year, we had some really strong data at ASCO GI with the 702 study around the celecox abuse. I think that, I think, has filtered its way in and doctors are really starting to kind of take hold of that. So we saw excellent growth in colorectal, excellent growth in breast cancer and immunotherapy monitoring. And then as we said on the call, when doctors start using our product and they want to kind of expand and start to use it for other tumors. So there's a little bit of everything when it comes to the histologies. We also saw an incredible record in new patients. And that's really one of the -- I think one of the most important metrics to look at is are the doctors continuing to order not just on patients that they ordered a year ago, but when a patient walks in the door, are they choosing our tool to make a decision? Or are they choosing a competitor tool or they're not using MRD at all? And I mean, we saw just absolute blowout record twice higher growth than we've ever seen before in new patients. So we think that's a very good sign. And of course, it's a mix of new customers that are coming in for the first time and then customers that have started using us and are now starting to, I think, broaden their use either to more patients or to more use cases.

Terrific. And maybe just as a follow-up for Solomon or Steve or anyone on the team here. Just in terms of the clinical readouts, you went through a lot of the studies that are ongoing in breast. You talked about the treatment on molecular response. Could you just give us a sense over the next, say, 12 or 18 months? You mentioned IMvigor011, which I think could be guideline inclusive. So we have that one coming up. What are some of the other ones that you would point to across the next 18 months or 2 years? I'm sure they're all important, but are there any more that are important than not that could actually be either guideline inclusive or really drive some meaningful change in practice?

Yes, Dan, that's a great question. I mean I'll just make a couple of comments and then maybe Solomon or Alex, if you guys want to comment on. I think first IMvigor011. I mean that's obviously a big one, FDA-enabling trial. We believe the results will be released in the future. We're super excited about that. And a very good indication, muscle-invasive bladder cancer. Hopefully, we'll have also some new data readout at ESMO this year, which I think will be good. We talked about the gastroesophageal and liver papers. Those have actually just been published, which is super exciting. That's one of the important steps to kind of putting yourself in a position to get coverage is having a peer-reviewed publication. Solomon, do you want to walk through a couple of the other or maybe Alex? I know we talked a little bit about data, when the next readout from that maybe. Anything else you want to highlight?

I think the other one that we've talked about before are the NRG sponsored colorectal trial, the CIRCULATE U.S. and there's a few other CIRCULATE trials globally that are likely to have either an interim or a primary readout over the next 18 to 24 months. And that includes, hopefully, the deescalation arm VEGA from the Japan CIRCULATE trial. So I would just highlight those 2 in CRC that could definitely make a difference for guidelines and beyond. And we'll keep you everyone up to date.

The next question comes from Puneet Souda with Leerink Partners.

Steve and team, so first one, Signatera, again, congrats on the quarter and the guide raise here, Signatera volumes quarter-to-quarter really strong. Could you talk a little bit about was there any contribution from post-ASCO pickup? There was a newfound appreciation for MRD at ASCO. Obviously, that crowd has known MRD for years, but it appeared it lifted more. And then I would love to get your view and maybe from Mike as well in terms of how should we be thinking about and how should investors think about the penetration of Signatera today? And the continued room for expansion, how you're thinking -- how do you calculate the penetration in various indications?

Yes. That's a good question. So yes, I mean, obviously, ASCO this year had enormous amount of oral presentations, posters on Signatera, and there was just a huge buzz at the conference around MRD. I mean everywhere you went, talking about MRD. So a lot of excitement coming out of that. I think we did see a lot of strong momentum in the kind of last month of the quarter coming out of there after a lot of the presentations. So that's a great sign, I think, going forward. And I think that buzz is continuing. From a penetration standpoint, we think this is very underpenetrated, I mean, low single-digit penetration when you look broadly. And what we're really starting to see is that this opportunity is very, very broad. When you look at doctors, especially community practice, they start using for colorectal, then they kind of start with gastroesophageal, then they may order for lung, maybe order from bladder. I mean they really start to kind of go and expand throughout the practice. So as we move through those stages with the physicians, we're just realizing how underpenetrated the opportunity is, but how we have a presence in all of these offices. So we're -- we now have this sort of very broad footprint that has set up a significant amount of data. We've built all this infrastructure. We have a lot of coverage in place. We have all of these studies underway. And we're in a great position to now increase volume over time based on all the infrastructure that we've put in place.

Got it. And then on the PROCEED and FIND trials, I just wanted to understand your strategy, the timing. This is clearly a hard problem to crack. We saw a trial failure. In short, it was -- it meet the primary endpoint, but it was below the NCD. And that company subsequently licensed the technology from another company. But just could you talk about the technology and the performance, the sensitivity, the AAs? What are you shooting for? When do you think you can -- when can we see the data? When can we see an FDA approval, reimbursement and then launch? Obviously, this market is -- there's a product on the market and it looks like now there is an entrant that's getting more of a boost. So I just want to understand the timing and how you're thinking about this market.

Yes. Let me make a couple of comments and then maybe hand it over to Solomon -- or excuse me, to Alex to talk further. But I'll just say first, we have a long history of doing in-house R&D and developing products ourselves, entering into new markets successfully and also competing very well in highly competitive markets. So we think we're in a good position long term to make this a very significant component of Natera's overall business. From a timing standpoint, the first -- the next major readout is going to be the PROCEED trial. And PROCEED, if you remember, was collected exactly how you would collect samples in the FDA protocol. So it's not some other type of protocol, it's effectively drawing the blood and then the patient goes and gets colonoscopy. So it's a screening protocol that exactly aligns to what you would see in an FDA trial. So when the results from that readout, we've already enrolled 3,000 patients. We have all the samples. They're being run. It's going to be read out, I think, we said kind of late fall. From there, you're going to get a very, very good sense of how the test performs, particularly in -- I think that the focus is going to be in advanced adenomas and also on the specificity. So I think that's going to put us in a great position to really have much more of an acute sense of what the performance is going to be in the FDA enabling study. And I think that's a little bit different maybe than the approach that some others have taken historically. And then if you look back to the CRC data that we read out earlier this year, I think, kind of shortly after JPMorgan or maybe kind of right around that time frame, if you remember, we had a lot of screening identified asymptomatic colorectal cancer patients in those cohorts. So again, a little bit different from the strategy some others have taken previously where they don't really have kind of the screening detected asymptomatic patients included the cohort, and we think that, that reduces the likelihood of drop off as you move forward. So look, stay tuned for the readout, super exciting. For FIND, that trial is already up and running. We've already enrolled patients, and we think that can be complete enrollment potentially kind of late '26, and we can be in a position to read out the results and submit to the FDA in 2027. Alex, do you want to add anything?

Yes. Great question. Yes, the only thing I'll add is we're very aware, right, the degradation can occur. And we do believe that probably the biggest source of degradation is poorly matching the FDA study with the case-control studies that are being used to assess early assay performance. So we've really taken a very thoughtful strategy of really launching the PROCEED study and using that as the basis for the FIND study, right? So the study really rolled from PROCEED into FIND. So the enrollment criteria, the processes for enrolling patients are very, very similar, if not the same. And this allows us to really accrue samples from PROCEED, which hopefully are matched almost kind of one-to-one with the final FIND study. And then the last thing I'll say is that while getting enough prospectively collected colon cancers may be difficult, actually collecting enough advanced adenomas to read out a very good performance estimate is much easier, right, because the rates of advanced adenoma are between 5% to 10%. So from PROCEED, we're going to get hundreds of advanced adenoma samples. So this allows us to actually read out with a well-powered cohort and really estimate what the final performance of the assay is going to be. So we're doing that. We're going to read out some data end of the year, and there could be additional readouts, right, before the final readout for the FIND study. And then Steve mentioned, FIND is going. It's enrolling. We're very, very excited. And right now, we're kind of guiding to readout of that study in 2027. But as we can -- get closer to that date, we'll kind of further refine our guidance.

Got it. Super. And then just if I could squeeze one in, just given the number of inbounds that I'm getting very quickly. Briefly, if you could provide me a number of product launches this year, just if you could encapsulate that? And how quickly can you monetize the AI initiatives that you talked about and turn them into assays and products and to start to see revenue there?

Yes, I'll take -- I'll comment and then Alex jump in again. But yes, on product launches, I mean, we just announced Fetal Focus. We're excited about that. We launched Genome earlier in the year. As we said, we've got several other things coming, largely focused around MRD. So we'll -- I think stay tuned. As those launch, we'll give you guys an update. But lots of cool stuff happening, lots of MRD- related activity that's on track coming down the pipe. So the vast majority of our investment there is focused on MRD. And then on the AI side, I think there's -- we talked about a couple of different things. One is sort of efficiency improvements in UX tools. Those are going to be rolled out over a period of time. Some of that works just beginning. Some of that work has been underway. That's really more cost reduction and user experience. The more technical kind of medically focused stuff is super exciting. And we think there, there's a couple of different opportunities to commercialize. I mean one is you've seen some of these big multi- $100 million, multimillion dollar deals with pharma companies or partnerships. And we think we have an incredibly unique dataset, an incredibly unique set of tools and foundation models that are going to be important, very important for pharma going forward. And I think this, for the first time, kind of puts us in a position to be doing those very large deals. And then the second is we're going to be commercializing a lot of the stuff through our current diagnostic platforms, either as kind of add-on capabilities alongside our existing tests or as stand-alone biomarkers.

The next question comes from Catherine Schulte with Baird.

Maybe first, you talked about the $250 million to $300 million of revenue from potential Medicare coverage of noncovered indications. Can you just give us a bit more in terms of details on the time line for some of these submissions? And how should we think about those being paced going forward?

Yes. Good question. So yes, I mean, for that, we basically just looked at all the noncovered indications and the volume that we have there that we're not billing and we said, what would it be worth if we got covered for that basically in the next kind of 12 to 18 months or something in that time frame. And you get $250 million, $300 million in revenue. So we're -- there's a lot of upside opportunity from the business that is already coming in just simply from getting these coverages. And you can believe this is a big focus of ours is to get these commissions in and get coverage. So I mean, I think we said in the prepared remarks, at least 7 or something in that range. I was going to call today where we went over opportunities for 15 different submissions. So I think there's going to be a lot coming. But you -- I think as you've seen, it's not always as easy as just doing a submission. You have to have the right data and you have to make sure the trial is done the right way. And so we've developed a significant expertise in doing the right MRD trials and submitting those and getting coverage. And that's what we're doing, again, in all these other indications.

Okay. Great. And then you highlighted, I think over $150 million in breast cancer clinical trials. Is that signaling real focus on breast in terms of prioritizing additional indications? You've got a competitor potentially coming who has a large presence on risk of recurrent side for breast cancer. So just maybe talk through how you view your competitive position in that cancer type?

Yes. I think breast has always, from the very beginning, been a major focus for us, along with initially colorectal and immunotherapy monitoring and now really pan cancer. So if you look back at some of the trials we presented, I mean, I think the DARE study, which now has like 2,000-plus time points started in 2021, so 4 or 5 years ago now. So this isn't like a sort of a new thing. I think there's continued investments that are new, like, for example, the TEODOR study. But we've been investing heavily into breast the whole time. And like we said, we've invested and are in the process of investing over $150 million in -- just in breast cancer alone in clinical trials. And that's in our budget, that's in the forecast that we've shown. So the point is that it's a big effort to do these things, and there's a lot of different trials that need to be done. And we're already doing it, and we think it's going to be very hard for someone to come and sort of replicate that. But obviously, breast is a big opportunity. There's a chance to really help a lot of patients and it's a cancer, I think that's very near to me and many others at the company as well for personal reasons.

The next question comes from Doug Schenkel with Wolfe Research.

First, on gross margin. In a period of strength, how much was gross margin actually adversely affected by the launch of whole exome? I'm just trying to get a baseline in advance of whole exome gross margin improving over the next few quarters, especially given the first half strength. So that's the first one. The second is on volume trajectory. You've been signaling that we should be modeling an expectation for 12,000 incremental clinical Signatera units each quarter. The trailing 4-quarter average is already about 16,000. At what point would you consider bumping that up? And the last one is on revenue strength and operating spend. So in the first quarter, on a really strong top line, you increased operating spend. This quarter, again, really strong at the top line, but you maintained your operating spend guide. Is this a sign that you are where you want to be in terms of things like headcount and number of R&D programs for the next several quarters?

Yes. I think, Mike, you can probably run the table there.

Yes. No, thanks for the question. So Doug, remind me the first one again. I should have been writing those down, and you gave me a good list. I can go...

First one, on the gross margin.

Yes. Yes. So the gross margins, I think ex the big step-up we had in new patients, I think it's fair to estimate that the gross margin progression sequentially would have been kind of similar to what we saw in Q1. So I think you would have had that kind of same kind of steady improvement in gross margins. And that really would have been driven by the bump up we had. Again, we had another bump up in Signatera ASPs primarily, and we had another strong ASP quarter in women's health, which I was very pleased to see. I want to see those -- the strong ASP traction we've had there. I want to see that kind of maintain, and we definitely saw that in the quarter. Give me the next one again.

You beat by 16,000 on average the last 4 quarters. You've been guiding up to 12,000. At what point are we moving that up?

Yes. I mean, I think you have to move it up modestly, but I just -- I would just caution you not to anchor on any 1 quarter. And the reason for that is just that there has to be some randomness there quarter-to-quarter, where we'll have -- we'll fluctuate up and down. So you got to allow for that. But beyond that, I mean, in terms of kind of fundamental drivers, Steve covered them. I mean we're really in a fantastic position here where the operations are running incredibly smoothly. We're kind of on the other side of a lot of very daunting challenges that we had to undertake to launch this category and things are rolling. The data is coming in that we started years and years ago is reading out. So it's a great time, I think, for the whole space for MRD, great time for patients. So I mean, I think I would just -- without kind of laying out like a specific number, I'd say bumping up modestly versus our prior and just look out for fluctuations, that's to be expected, and that's totally normal.

The next question comes from Rachel Vatnsdal with JPMorgan.

So I wanted to push a little bit further on the sales rep dynamics. So you talked a bit about expanding your sales force. Can you walk us through how large is your sales force at this point? And where do you think that needs to be over the medium to long term? And then just specifically on some of the recent sales rep adds, how should we think about the productivity for those new reps as we get into later this year and into 2026 as well?

Yes, it's a good question. So I think traditionally, we sort of have like 150, 175 oncology reps, something in that range. I think we've executed kind of a meaningful step-up. That was completed during Q2. So a lot of those folks are kind of just coming out of training or kind of just getting their feet wet out in the field, meeting customers and so forth. So in our view, normally, it 6 to 9 months for the reps to really become productive. And that's just when you think about like all the complexity of the material, 100 peer-reviewed publications, building relationships. So we're in this kind of dynamic now, which I think we called like a slingshot effect on the call where we have this built-in expense line of these people that we've hired, but they're not really kind of driving productivity yet at this point. As we look into when they do become productive, what are sort of some of the metrics that we look at, obviously, we look at the number of new accounts that they're bringing on, account retention in the business, their ability to add on new doctors within the practice, their ability to expand from one tumor type to the other within the particular practice. So I would just say those are kind of the types of things that we look at. We don't really have like a -- just given kind of the growth phase that we're in, we really -- we don't have like necessarily an immediate like revenue that every rep has to hit within x number of time, but there's certainly a lot of attention on the growth trajectory and the amount of return that's being driven by each rep.

Great. And then for my follow-up, on Signatera, it sounds like you guys had another standout quarter there on new patient adds. Can you explicitly tell us how many new patients were added in the quarter for Signatera? And any color on what indication or use cases you primarily saw those in? And then as a follow-up to that, how should we think about this in terms of volume expectations for Signatera as we look into 2026?

Mike, do you want to comment on new patients?

Yes, on new patients, I mean, just as I was just covering with Doug, I mean, if you had just a normal kind of mix that we have, it would have been about 40 basis points. And so this was -- this is multiples of that, as Steve described in the call. I don't want to get into like laying that out as a KPI that we've been kind of giving all the time because I know that, that is -- the growth in new patient starts is a very volatile metric for the business. I mean, I think in terms of kind of looking forward into 2026, I mean, it does give me some confidence now if you just look back -- just look at that chart on the volume growth and the consistency of that. I'm actually surprised with like how consistent that has been. That plus just the -- just when you go to the academic conferences now, it used to be that MRD was sort of like a new thing and it's to be examined and there's interesting data. And now I just feel like the tone has kind of shifted at those things where this is -- people doing MRD. I mean this is going to be something that it looks like it's inevitably part of the standard of care and that gives me a lot of confidence in the kind of the trajectory of the franchise, both rest of this year '26 and beyond.

The next question comes from Tycho Peterson with Jefferies.

I didn't hear you mention LATITUDE, which I think was on deck for a mid-'25 launch tumor naive. You've kind of mentioned and then a question on how many products are you launching more coming in MRD. But the LATITUDE get pushed out, what's the latest there? And then have you ever sized the TOMR opportunity for Signatera? I think that's certainly very interesting.

Yes. Solomon, do you want to take this or Alex?

Sure. Yes, we're -- thanks for those questions, Tycho. On the TOMR side -- or excuse me, on the LATITUDE side first, we're very excited about the progress there. So we presented excellent data recently, and we announced that sensitivity looking very good. I think at 81%, specificity at 97% on a per-sample basis, we see that as competitive with any other tissue-free test on the market. And we're already getting a lot of inbound requests and interest on it. So we're in the process of bringing that to our customers, and we'll talk more about that in a future update. On the TOMR side, we're really excited about TOMR. It's a concept we've been talking about with physicians and with investigators and with the investor community now for a while. I think -- the way we think about the size is really the surveillance setting for all the tumor types where Signatera can be used because that any of those patients who are being monitored for recurrence, if they ever turn positive, which some percentage unfortunately will, those patients become eligible for some intervention. And roughly between 1/4 to 1/2 of those patients will be negative -- excuse me, we'll be positive on a reflux scan and will be treated according to standard guidelines for treating metastatic disease. But the other half now up to 3 quarters, as we saw from the DARE study, will be negative on a scan. And that means that they're going to be looking for something else. Whether that's escalated imaging, which is the current standard, do a different type of scan, do it more frequently or they become eligible for a novel clinical trial where they can get treated directly and look for that clearance of the ctDNA. So I think there's going to be more and more trials coming out of this nature. And -- but we see the overall opportunity as all recurrence monitoring.

Okay. That's helpful. And then maybe shifting over to organ. MolDX has proposed some changes to the transplant LCD for solid organ allograft rejection. I know this doesn't directly impact you, but, a, have you had communication with them? Are you confident it won't be an issue? And then one question we've gotten is, is there any risk that this could eventually spill over to MRD just in the whole concept of capitating the number of tests they're willing to cover?

Yes. I'll take that. So I think first on LCD, I mean, we see it as upside for us. We're not in a position where we're kind of running 2 different assays like kind of running a DNA assay, running an RNA assay and kind of billing for them separately. So our organ health test is DNA only, and there's sort of one bill. So we're not impacted by that at all. And then the surveillance piece, we see as upside. And actually, when we kind of look at the cadence, we see it as upside for us. So we're excited about that. And organ health, like we said on the call, I mean, we talked mostly here about oncology, but we're doing really well. And we're seeing a lot of big major academic centers switching over to us. That's across the board, kidney, heart and lung. We've got a ton of great data that's been published, very unique features that set us apart. So we're excited about continuing the opportunity in organ health.

And risk, just this concept of capitating number of tests by MolDX could spill into MRD?

I mean, I think that already exists in many ways, right, with these sort of bundled reimbursement where it doesn't really matter how many tests they run, you're going to get paid a certain amount. I mean that's -- that already exists in a significant portion of the business. And then there's other tumor types where they have already said, "Hey, this is the cadence that we're going to reimburse for." So I don't think it's a risk. I think it already exists where they kind of look at what they think the appropriateness of ordering is. And in some cases, they put specific guidance in place. But normally, what we're seeing is the doctors order the test kind of roughly around the cadence that MolDX sort of kind of is aligned with. So I don't really see it as -- we don't see that as any real risk at all.