Natera, Inc. (NTRA) Q4 2025 Earnings Call Transcript

Welcome to Natera's 2025 fourth quarter financial results conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a Q&A session. To ask a question at that time, please press star followed by one on your touchtone phone. If anyone has difficulty hearing the conference, please press star zero for Operator Assistance. As a reminder, this call is being recorded today, February 26, 2026. I would now like to turn the conference over to Michael Brophy, Chief Financial Officer. Michael, please go ahead.

Thanks, Operator. Good afternoon. Thank you for joining our conference call to discuss the results of our fourth quarter of 2025. On the line, I'm joined by Steve Chapman, our CEO, Solomon Moskovitz, President, Clinical Diagnostics, alex selection general manager of oncology and our chief medical officer and john fesco president chief business 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.notera.com a replay of the call will also be posted to our ir site as soon as it's available starting on slide two during the course of this conference call we will be making 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 10K or 10Q, in the Form 8 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 being made as of today, February 26, 2026. If this call is replayed or reviewed after today, the information presented during the call may not contain current or accurate information. The Terra disclaims any obligation to update or revise any forward-looking statements. We will provide guidance on today's call, but will 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 great thanks mike let's get to the highlights on the next slide.

We had a fantastic quarter. We processed about 924,000 tests and set another record for MRD clinical unit growth with 225,000 tests processed in Q4. MRD clinical units grew about 56 percent compared to Q4 of 2024. We generated roughly $666 million in revenue in the quarter, which is about $6 million ahead of our pre-announced in January and represents approximately 40% revenue growth over Q4 of 2024. We were very pleased to generate a gross margin of 66.9% in the quarter, which wasn't part of our pre-announce and was well ahead of our expectations. All of that progress led us to generate over $107 million in cash flow in 2025, even as we doubled down on growth investments throughout the course of the year we're off to a great start so far in 2026 and we are excited to initiate our guide for the year we expect to generate between 2.62 billion 2.7 billion in revenues gross margins between 63 and 65 percent holding sgna stable while we make targeted investments in r d with the expectation that we generate another strong cash flow year in 2026. Mike will spend a lot more time on this topic later in the call. We've had a lot of exciting news since the JPM conference in January, including publishing the outstanding performance of our latitude tissue-free MRD test, which has now been submitted to MULDX, and launching the 21-gene fetal-focused single-gene NIPT test. Data on fetal focus was just awarded an oral plenary presentation at the Society of Maternal Fetal Medicine Conference, the only single gene NIPT to earn that honor. It's worth reflecting for a moment on the progress we made in 2025. We had a transformative year financially with 40% quarter-over-quarter revenue growth and significant gross margin expansion, while at the same time continuing to invest in our future. In a few years, when we look back on it, I think the key investments we made in our commercial channels, product launches, and clinical studies will prove to be engines for continued growth. You can see here on the page just a few of the product highlights. We significantly expanded our MRD product portfolio by launching the genome version of Cignatera and the Latitude MRD test, both of which complement Cignatera beautifully. We delivered the strongest year yet for Cignatera data generation, highlighted by the Invigor011 publication in the New England Journal. Then, at the end of the year, we welcomed foresight diagnostics to the fold, which gives us the phased variant technology, which unlocks the next level of ultrasensitivity that's already paying dividends, as we'll discuss today. We also advance organ health and women's health with significant investments in products like fetal focus and key studies like the randomized ACEs EMB trial in organ transplants. Okay, let's get into some of the business trends on the next slide. I want to jump straight to MRD clinical unit volume. Q4 represented yet another record growth quarter. Based on our internal data, we estimate that more than 50% of oncologists in the United States ordered a signatory test in the quarter, which just shows you the extent to which MRD is rapidly becoming a part of the standard of care for many cancer patients. Physicians continue to show a desire to adopt MRD broadly in their practice, which plays to our strengths, given the breadth and quality of our data. We're off to a great start so far in Q1. The next slide shows revenues, which was another area of significant outperformance this quarter. As I mentioned, we came in about $6 million ahead of the pre-announce on very strong overall volume growth and another quarter of sequential improvement in ASPs. We had an excellent oncology quarter and continue to see strength in women's health and organ health. Signaterra ASPs stepped up to roughly 1,225 in Q4. We had about 60 million in true ups this quarter consistent with our pre-announce as cash collections continues to accelerate and we posted another record for DSOs at 47 days compared to 68 days just in Q4 of 2024. The next slide shows our gross margin traction over time and we had excellent margin execution in Q4. Top line gross margins were a record as i mentioned at 66.9 percent and we had about three percent of that as benefit from the revenue true ups stripping out the true ups we posted a record organic gross margin quarter at 63.7 percent along with strong asps we had a very lean cogs quarter in q4 which drove significant organic step up of 240 basis points just compared to the third quarter looking into 2026 and beyond we've got a strong set of margin expansion opportunities and we think the cash collection trend continues to bode well for asps into 2026 to further improve asps we've submitted for much broader medicare reimbursement for signatera as a reminder a portion of the tests that we perform today are indications that aren't yet covered by medicare but where we submitted for coverage. We have a good track record of getting coverage given the quality of our data, so this could be an opportunity. We are also starting to see commercial payers come on given the breadth of progress that's been made on the biomarker states. In addition, we are increasingly seeing opportunities to deploy AI-enabled workflows to help ensure that we get reimbursed for covered services. Mike will spend a little more time on this in his section. We have several COGS opportunities underway as well that will hit throughout the year including both lab workflow opportunities and also deployment of ai to reduce many routine manual steps all in we're in a good position for margin expansion going forward okay with that let me turn it over to solomon to discuss more details solomon thanks steve getting into some of our recent data and announcements I want to begin in our women's health business with Fetal Focus, our next generation single gene NIPT.

This test, powered by Natera's ultra-sensitive linked SNP technology, directly analyzes fetal cell-free DNA to screen for serious inherited conditions. It addresses a significant clinical unmet need by enabling fetal risk assessment when the mother is a carrier of a recessive mutation, but the father is unavailable for screening, a common real-world challenge in prenatal care. Our expanded 21 gene offering, announced in early January, is the broadest single gene and IPT product in the market with impressive flexibility, as it can either be ordered up front along with the Horizon carrier screen, or it can be ordered later after Horizon carrier status has already been reported. The test performance is robust, with overall sensitivity across conditions of 96%, and overall population-weighted specificity of 98%. The competitive strength of this product offering is fueling meaningful growth in new OBGYN and MFM accounts. Of course, a major source of strength for fetal focus is its prospective blinded validation in the EXPAND trial, with confirmed genetic outcomes on all positives and negatives. The EXPAND trial was selected for an oral plenary presentation earlier this month, at the Society for Maternal Fetal Medicine annual meeting. Scoring an oral plenary at SMFM is extremely rare, even in the age of cell-free DNA, so it's a strong indicator of the scientific and clinical relevance of this work. We're pleased with the feedback during and after the conference, and we look forward to submitting these results for publication in a leading peer-reviewed journal. We also look forward to significant new product enhancements in 2026 for our Women's Health customers to be announced in the future. Moving to the organ health portfolio now, we continue to invest meaningfully in proving the clinical utility of Prospera donor DNA monitoring across all organ types. In addition to the early detection and treatment of graft injury, our vision is that Prospera can also help reduce unnecessary biopsies and unnecessary immunosuppression. In the field of heart transplant, we recently completed enrollment in the novel ACEs EMB trial, the first randomized controlled study directly comparing surveillance with Prospera against protocol endomyocardial biopsies, or EMB. Protocol EMB, which often occur monthly or even more in year one post-transplant, is currently the standard of care for the approximately 4,500 patients per year in the U.S. who receive heart transplants. So the goal of the trial is to show that patients can safely avoid most of those protocol biopsies. ACEs EMB has enrolled over 300 patients across 17 transplant centers in the U.S., randomizing participants one month after transplant to surveillance either with Prospera or with EMB in a two-to-one ratio, with clinical a follow-up for 12 months. We look forward to reading out the results in mid-2027 once all follow-up data has been collected and analyzed. Complementing this approach now on the lung side, new data recently published in the journal Transplantation Direct highlights how persphera-guided monitoring can reduce unnecessary surveillance biopsies for lung transplant recipients. Lung transplant patients are typically monitored with transbronchial biopsies, usually five times or more in the first year after transplantation. These procedures are invasive, risky, and associated with significant potential morbidity. In this study, the Ohio State University Wexner Medical Center performed a prospective study incorporating Prospera monitoring into routine care. Based on low-risk Prospera results, clinicians elected to forego the nine-month surveillance months biopsy in about 75% of patients. Over the ensuing three months, those patients experienced no significant differences in acute rejection rates, lung function metrics, or immunologic markers, compared with patients who did undergo the biopsy. This is an important validation of the biopsy reduction concept in lung transplant, and we already see a driving engagement among clinical leaders in thoracic transplantation. Strong clinical data like this has continued to fuel meaningful share gains for Prospera in thoracic as well as renal transplantation. And with that, I want to turn it over to Alex to discuss our most recent data in oncology. Alex?

Thanks, Solomon. Here we're highlighting what we view as exceptional momentum in bladder cancer going into the ASCO-GU conference. At this single meeting alone, we have a strong set of abstracts and oral presentations that collectively reinforce the critical role of Signatera across the bladder cancer continuum, from risk stratification to treatment selection to enabling new care pathways like bladder preservation. A key theme here is, can we spare the bladder, which we think is one of the most important clinical questions in the field. Studies such as InBlade and Retain show that CTA-negative patients who underwent active surveillance had similar outcomes to CTA-negative patients who had a cystectomy, suggesting that Signatera can identify candidates for bladder-sparing approaches, potentially avoiding or delaying radical surgery in appropriate patients. And finally, data sets like Niagara point to the next frontier, combining ctDNA and urinary tumor DNA to provide complementary insights into residual disease risk and local disease biology, a direction we believe can further strengthen patient selection for bladder preservation strategies and expand market size across urologic malignancies. The takeaway is ASCOGU is one conference, but it's a great example of the consistent drumbeat we're driving, using high-impact data to expand Signatera into new indications and to deepen penetration across existing workflows. And importantly, we are executing this playbook across multiple histologies. Moving to the next slide, we're highlighting exciting interventional data in head and neck cancer from the Phase II Synergy trial and frontline, recurrent, or metastatic head and neck squamous cell carcinoma. What makes Synergy especially important is that it's not just showing ctDNA's prognostics. It demonstrates the benefit of ctDNA-guided treatment and adaptation in real time. Here's the clinical problem Synergy addresses. In advanced head and neck cancer, physicians face a difficult sequencing decision. start with immunotherapy alone and risk undertreating patients who need rapid cytoreduction or start with immunotherapy plus chemotherapy and risk overtreating patients who may not need prolonged chemotherapy exposure. The question is whether we can achieve the best of both worlds using Cignatera-guided adaptive treatment approaches. In the study, patients started on either pembrolizumab alone or pembrolizumab plus chemotherapy. And then signatory CTN dynamics were used to escalate or de-escalate chemotherapy in real time. The first important result is that 74% of patients de-escalated the chemotherapy at least once for the median of two chemotherapy cycles delivered versus the typical six cycles. This is a meaningful reduction in chemotherapy, and the question is how that affected patient outcomes. Amazingly, the outcome showed an objective response rate of 63%, which is really strong compared to the 19 to 36% seen in the original registrational trial. And importantly, the rate of grade three or higher toxicity was only 48%, which is a clear improvement over historical precedents. The punchline is that Synergy supports a future where Signaterra becomes a treatment navigation tool in the metastatic setting, in head and neck cancer, and across other cancer types, helping physicians and patients optimize their therapeutic strategy in real time. Furthermore, this head and neck indication is already covered by Molde-X under our IO treatment response monitoring indication. We expect multiple similar studies to read out over the next few years, a testament to our investment into prospective clinical evidence generation that started many years ago. With this, let me turn it over to John to discuss progress in our Molde-X submission and our phase variant technology. John?

Thanks, Alex. I'm excited to announce that Natera has submitted our first tissue-free MRD assay to mold DX in colorectal cancer. Latitude is a methylation-based assay that delivers MRD insight without needing tumor tissue, making it a strong complement to our flagship Signatera platform, enabling MRD assessment even when tissue is unavailable, insufficient, or delayed. In January, we published clinical validation from the Galaxy study in NPJ Precision Oncology. In a large dataset spanning 195 patients and 1,230 time points, latitude MRD positivity was highly prognostic for recurrence, with a hazard ratio of 10 post-surgery, a hazard ratio of 31.9 in post-treatment surveillance, 84% longitudinal sensitivity, 97% sample-level specificity, and a 4.6-month median lead time ahead of imaging. When you look across published tissue-free MRD assays in CRC, we think these performance metrics are excellent. Importantly, the data also support clinical actionability and include a predictive signal for adjuvant chemotherapy benefit. Our recently submitted technical assessment is a key step towards broader reimbursement and scaled adoption in CRC, and another driver of MRD growth as we expand access and streamline ordering. We also look forward to validating this tissue-free technology for other cancer types later this Beyond latitude, Natera also has a full suite of Signatera submissions now under review by MoldX in a broad range of histologies, and we are excited to further expand insurance coverage for cancer patients. Moving on, I also want to describe an exciting new technology that we have integrated into our tumor-informed CignaTera platform, phased variants, that is driving our detection thresholds down to unprecedented levels, below one fragment of tumor DNA in a background of 10 million normal copies. As a reminder, Natera closed the acquisition of Foresight Diagnostics in December and immediately integrated phased variants into our CignaTera platform. where we expect it to enhance performance in MRD across solid tumors. This product is available today for research use and will be launched clinically this year. So what are phase variants and why do they matter? Tumor-informed MRD testing has traditionally focused on identifying ctDNA with single tumor-derived variants. Phase variants take this concept further. Instead of looking for a single mutation on a fragment of ctDNA, we look for two or more mutations on the same physical DNA fragment. What makes phase variance powerful is not simply tracking more mutations, but rather how this approach fundamentally reduces the impact of background errors and enables vastly better sensitivity. Background errors that are routinely introduced through sequencing chemistry, artifacts, and biology can become an issue at very low tumor fractions. but with phase variance the probability that such errors identically replicate multiple variants on a single fragment is so low as to be almost zero so that dramatic reduction in error is what enables confident detection at thresholds 10 to 100 times lower than conventional approaches analytically this translates into an lod95 of approximately three parts per $10 million and detection below one part per $10 million. And this technology is backed by very strong patents. Clinically, we believe this further widens our moat in MRD test performance. It's also a fantastic addition to our pharma services offering, generating significant excitement with partners. In fact, we've already signed an important prospective pivotal trial, which we'll be announcing when it kicks off. With this, let me turn it over to Mike to review the financials.

Great. Thanks, John. The next page is just a summary of the financials compared to last year. You can see what an impactful year 2025 was in terms of revenue scaling and gross margin improvement. Steve noted that we put up a very strong gross margin here in Q4. And while the core ASP and COGS trends do look very strong, I think we also benefited from a few tailwinds specific to the quarter. For example, we had a nice high margin contribution from pharma in Q4, and our reported units ratio to test a session in the lab was a little higher than usual. That tends to help gross margins because we only book revenues on the tests that have been fully reported out. I would also note that we significantly narrowed our operating losses in Q4 as compared to last year, even as we significantly stepped up our investments in OPEX. We actually generated net income in Q4, although that was helped along by a one-timer, which was a below-the-line deferred tax item related to the foresight acquisition. We think our path of profitability remains very clear, and we are sticking to the plan we've laid out in the past. We fully intend to keep our foot on the gas in terms of investing in the business as we grow our way to profitability. Finally, on this slide, you'll just note that our balance sheet remains pristine with over a billion dollars in cash and securities. Okay, let's get to the guide on the next slide. Steve previewed the key pieces on revenues and gross margins, and we are well positioned to generate cash again this year. I'll just remind you that consistent with prior years, this guide does not presume any meaningful contribution from revenue true-ups. We will likely have some true-up benefit in 26, but I expect true-ups as a percent of revenue to decline as we continue to wring out the towel on all of the operational improvements we've launched in revenue cycle management over the last few years. Beyond that, it's important for you to think about our underlying trends in unit economics, and I think guiding with future true-ups stripped out of the forecast makes it easier to understand and model the business. That's important context for evaluating year-on-year trends. For example, our gross margin for 2025 ex-true-ups was about 61.5%, So centering the guide at 64% for this year represents our expectation that we continue to ring the bell on COGS improvements and additional ASP games. I'd also note that we are exhibiting some caution on this initial gross margin guide given, one, some of the drivers of the Q4 improvement may not repeat every quarter, and two, we've got some products launching that aren't yet reimbursed, as John mentioned. but when I reflect on the coverage roadmap that John described, I can certainly see a path to margin outperformance this year. Okay, on the next slide, this slide gives you that same bridge for revenues. Backing out the 2025 true-ups, you can see that the midpoint of the guide implies roughly 25% growth over what was a monster year for us in 2025. The revenue guide presumes continued growth in women's health volumes and ASPs and another strong year of growth for the Oregon Health products. On Signatera, Steve called out that we are already off to a really strong start so far in 2026. The guide calls for another excellent year on volume growth, which we are poised to deliver on. On the Q3 call, I noted that we expect another net $50 bump to ASP for Signatera over the near future. Given that we are up roughly $20 in ASP for Signatera just in Q4, the guide implies another $30 or so in ASP growth embedded in this initial guide. Of course, that does leave us some upside room as the guides discuss potential for much broader reimbursement that's not embedded in this guide just to start the year, along with our kind of standard operational improvements that we expect to get. Just a note on the overall pacing of the quarters. We expect Signatera and Prospera to just grow sequentially quarter over quarter this year. And for women's health, I think it's worth baking in the usual seasonality that we see, where Q1 is a big volume quarter, Q2 is down sequentially, and we recover to Q1 levels in Q3 and Q4. Okay, the next slide here is just to give you some insight on the OPEX guide for the year. Overall, at the midpoints, we are slated to grow OPEX about 9.5%, just a bit better than what we previewed on the Q3 call, and well below the roughly 25% pro forma growth implied by the revenue guide. The components of the OPEX give some important insight on where we are as a company. After making the investments to get to the right size commercial channels, particularly in oncology, we are now in a place where we can drive substantial top-line growth while holding SG&A roughly stable in 2026. Our plan is to stay focused on 2030 and beyond by continuing to invest in best-in-class products and clinical trials. The major components of the growth in R&D include a substantial investment in the FINE trial for early cancer detection in colorectal cancer and the investments we are making in large clinical trials and technology development focus on MRD. I'll just reiterate once more that we are going to stay in growth mode, and if important new opportunities arise this year, we are not going to be shy about adding some short-term operating expenses to yield long-term results. And now let me turn it back over to Steve.

Thanks, Mike. In summary, we had a great year across the business, and as you can see on the slide, we had several exciting milestones anticipated as we move through 2026. Okay, with that, let me open it up to questions. Operator.

Thank you. If you would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. And if you'd like to withdraw that question, again, press star one. Your first question comes from the line of Catherine Schulte with Baird. Please go ahead.

Hey, guys. Thanks for the questions. Maybe first, just on signatory ASPs, on the Medicare side, a few moving pieces there with the ADLT surveillance coming down, but the adjuvant bundle rates going up. Can you just talk through the net ASP impact from those changes and how that factors into your kind of plus 30 annual guide?

Yeah, thanks, Catherine. Mike, do you want to take that?

Yeah, sure. Hey, thanks, got some good question yeah so the the the changes on the uh adlt rate and on the bundle roughly net each other out um given kind of the the mix that we've had in terms of um recurrence and um and bundles over the past year um so the the net 30 what that really what that embeds in the guide is us just continuing to execute on broadening the the percentage of time we're reimbursed for covered services for Medicare Advantage volumes and more progress in the biomarker states. It leaves as upside, you know, the additional coverage decisions and all the efforts that we have ongoing with mold decks that John Fesco was talking about on the call. So as I mentioned, I mean, I think, you know, the strategy with these initial guides for us over the last 10, 11 years has been to just start with a, you know, demanding but achievable kind of initial guide for the year, and that's kind of how I would characterize this ASP guide.

Okay, and then can you give us an update on Signatera mix by indication? If you were to receive a pan cancer indication on solid tumors from Moldyx, I guess, what would that mean for ASPs?

Yeah, I'll take that. So, yeah, I think we've kind of said before, You know, obviously, CRC, breast, bladder, you know, lung, some of the bigger ones there that were already covered for making up the majority. But, you know, there's a good 30, maybe 35%, something in that range that fall into kind of the non-covered bucket. You know, that's kind of where we've said, you know, if we can get coverage for the remaining Medicare indications, it could be, you know, based on the run rate, a couple hundred million dollars in gross profit and revenue. And we've submitted now for, you know, a significant number of additional indications that would, I think, capture the vast majority of, you know, the remaining outstanding histologies. And, you know, we have a good track record of getting Medicare coverage just given the significant amount of data that we've generated. So, you know, hopefully that remains as upside on the ASP, as Mike said.

Great.

Your next question comes from the line of Puneek Sudha with Learink Partners, please go ahead.

Yeah, hi guys, thanks for taking my question and first one, maybe just given the strong growth and signature that you're seeing here, despite the seasonality, despite the holidays, you put up a very strong number. Last year talking about sequential 8 to 10,000 increases, Mike, maybe for you, you know, how should we think about that number, sequential increase number this year? And on the data catalyst side, maybe could you remind us what's most, you know, sort of needle moving this year in terms of the data and any thoughts on NCCN? And just add a follow-up on prenatal.

Yeah, so maybe let me comment just for a second on, you know, some of the data and then, you know, maybe Mike, you can kind of talk about the pacing. And I don't know, Alex or Solomon, if you guys want to comment on the data. But what we've been focusing on is really generating a lot of evidence, you know, in a broader set of indications. And, you know, I think you're starting to see a lot of that come out. So we just had this, you know, interventional trial in head and neck cancer, which we think is a great indication. I think there's about, you know, 70,000 patients per year there. And I think last year, kind of the tail end of the year, we had a gastroesophageal study come out that was pretty significant. We had a pancreatic study come out that was pretty significant. So, you know, we're now generating the type of data in these other indications that, you know, we think can really move the needle and I think that that's exciting.

So Alex or Solomon, do you guys have any other studies that you want to call out specifically before, you know, before we talk about the pacing i think that that's pretty good summary i think the need if you just look at asco gu this year i was actually at the conference earlier today you know ton of excitement probably three or four pretty practice changing studies that you know we were commented on during the pre-read i would say pretty much at every other conference later this year probably five or six major ones, you probably will expect to see a similar drumbeat of clinical readouts. So, we're expecting data in breast, additional GI indications, IO monitoring, and then, you know, some of the larger prospective randomized studies should start reading out in the next year or two. As we get closer to that, we'll provide some additional guidance.

Yeah, and then just on the pacing, I mean, I'm kind of in the same place as I have been in terms of the approach i think the right way to to to model the growth of the signatory units is just to take the trailing four quarters you know average for the sequential growth units um that was you know 19.5 i think um last quarter and now i think if you do the math including the the q4 number i think it gets you to you know something like 20,000 units i think that's a decent bar for evaluating q1 and then as you as you you know continue to grow the reason why I like that approach is that it does update itself, and it kind of gives effect to the compounding effect that we have in the business, given that it's a repeat, you know, volumes per patient. And so I think that base expectation will just kind of continue to grow. Doing the last four quarters average just kind of smooths out any of the just the random oscillations you'll have quarter to quarter in terms of number of days or weather or holidays or what have you. So I think that's the right approach, and it keeps getting higher, and the business just keeps on performing better and better.

Okay, that's super. And then a quick follow-up on the fetal-focused product. I just want to understand your marketing approach today and your ability to take share in the market with an existing assay that is more often a single assay. You have two assays here. So maybe just, you know, walk us through the patient workup conversation, marketing of this assay. And how do you think, you know, how do you think about share gain in this? And how should we think about the growth in overall women's health from that share gain this year?

Yeah, I'll take that. I mean, I think, you know, the real question is, you know, really do physicians like the product? And, you know, from what we're seeing is there's significant interest in the fetal focus test. I think we're hitting all the right marks. I mean, we're seeing the volume really increase. And I think we're in a position to see that continue throughout the year. So, you know, from a marketing standpoint, our test works in a very similar way to other single-gene tests on the market from the standpoint of how it's ordered. um or what the flexibility is when you know when you order so you can decide either to order the test up front um you know and basically if the mother is is positive then the fuel focus test will will be run and i think that's kind of comparable to to you know how others do it um you know you have to sort of know the mother's positive before you can uh run the the fetal test and then i think separately although i i don't know exactly how others do it so you know i do take separately the um you know the other option is you can you know order the test um you know send the blood and then wait and and see if the mother is positive and then we can we can sort of reflex to it so you know there's different approaches um but we offer all the different approaches and you know i think it's uh you know we're flexible from the standpoint of how people want to access the test uh but we're seeing a lot of uptick um if you look at the smfm plenary presentation um you know certainly you know that's a prestigious selection uh one that we're excited about and i think that that speaks to the strength of the data your next question comes from the line

of dan brennan with td cowan please go ahead great thank you thanks for the questions maybe just on you know, kind of saying on Cignatera, can you just give a little color, you know, as we exited 2025, I know there was a question on pan cancer, but just walk us through kind of tumor types, kind of what you're seeing as the key drivers. And as we look into 26, for this continued kind of, you know, sequential growth in Cignatera, like is, are you seeing any, obviously in vigorous driving bladder, but across the landscape, like kind of what are you seeing and what's baked in? Just want to get a flavor of what's going on in the field.

Yeah. So yeah, I guess when you're looking at sort of across different tumor types um you know there's there's a lot of different activity across the board i mean you know if you if you just look at all the data that's come out over the last several years you know you highlight it in vigor i mean certainly that's been um you know driving a lot of momentum in bladder i think this you know this recent data that alex mentioned at asco gu looking at bladder preservation i think is going to generate a lot of excitement You know, but, you know, it's all the data that we generated historically now as physicians start to use the product, maybe they use it in one tumor type, they become comfortable with it, they like it, then they see data come out in another tumor type and they start using it, you know, in another tumor type. or maybe they start within a tumor type using it on one category of patients. They realize they like the data that's being generated, and then they expand within that tumor type to another category. So, you know, all of that together, I think, is powering the growth. There's not one, you know, it's not like there's one factor that's unlocking growth or that, you know, is going to really kind of change things. It's a big flywheel effect of having over 100 peer-reviewed papers. having a large, you know, commercial team, having a large medical affairs team, and, you know, being present in, you know, many, many offices now, seeing more than 50% of doctors ordering the products, and then continuing to invest in new clinical trials and, you know, rounding out the product portfolio with Ignis, Terah, Genome, and Latitude.

Okay, great. Thanks for that, Steve. Maybe just on one outside of things, Sarah, Mike, just in terms of the modeling for 2026 between women's health and transplant, I heard you say something in the prepared remarks about some seasonality in women's health. Can you just give us a bit more of a bridge on those businesses and how we think about whether it be price, volume, total revenue, anything to help with the model there? Thank you.

Yeah, sure. Yeah, so I think that for Prospera, for the Oregon Health products, I mean, I think they're going to just continue to grow kind of on a secular growth trend, right? So, you know, this was, you know, better than 50% plus grower in 25, and I expect another big year from Oregon Health this year. And that's really kind of driven by, I think, just the evolution of that market and the primacy that Sulfur DNA is continuing to exhibit in terms of caring for patients. For women's health, I mean, it's actually, you know, Steve mentioned, you know, we're off to a great start. Key one usually is our big quarter. You know, I expect, you know, just to continue to grow, you know, volumes in a kind of mid-single-digit range for women's health. And I think you can do better than that on revenues because there is, I think, juice of squeeze in terms of, you know, achieving price and gains as we've done the last couple of years. Let me pause there. I don't know, Steve, you want to compare or contrast? You want to add to that?

No, I think that covers it.

Your next question comes from the line of Doug Schenkel with Wolf Research. Please go ahead.

It's Doug. Thanks for taking the question. This is, I think, a follow-up maybe on Catherine's question earlier, and I'm sorry if I just misunderstood the answer, but on signature of volume and mix, what was the breakdown between exome genome and latitude in the fourth quarter, how are you thinking about mix in 2026? And how does that play into kind of upside and downside scenarios for gross margin? And then, you know, I guess sort of related, is it fair to assume that CRC will dip below 50% of total signatera and latitude for that matter volume as indications like breast and lung continue to accelerate and gain further traction this year? Thank you.

Yeah, good question. So yeah, I'd say on CRC, you know, certainly we think over time things will sort of normalize to, you know, meet roughly kind of what you would see in the marketplace from the standpoint of, you know, cancer prevalence. I mean, obviously breast is going to be the largest over time. And so I think CRC will normalize, but, you know, it's still driving, you know, a good part of the volume at this point, but we're already starting to see, while CRC is growing and we're maintaining our share there, you know, some of the other tumor types are really starting to accelerate, and I think that's, you know, that's great for us because we've spent the last, you know, eight years generating data in these other tumor categories, and now some of that data, like this head and NEC data is just coming out now for the first time, and we're in a position to capitalize on that. When you look at the mix of exome, genome, and latitude, I think the vast majority of volume is exome. We are seeing some interest in genome in certain physician offices and academic centers, and it's great that we can service that. You know, those that are interested in that, you know, we've sort of built in an increase over time there, and that's part of our, you know, existing model. And then from a latitude standpoint, I think the initial kind of idea there was, you know, there's a small portion of cases, you know, maybe 5% or something in that range where, you know, we're not getting the, you know, we're not able to get the tissue in CRC. and in those cases, you know, we can now serve those patients with latitude, but there's also another opportunity, which is just this sort of physicians who just want tumor-naive, and, you know, while we think the vast majority of people, and what we're seeing is the vast majority of people want tumor-informed, there is a subset that want tumor-naive, and that's a growth opportunity that we haven't really pursued, and I think that's an opportunity for us as well as we move forward. Hopefully, that gives you a little bit more color.

That was fantastic. Thank you very much.

Your next question comes from the line of Casey Woodright with JP Morgan. Please go ahead.

Great. Thank you for taking my questions. Maybe the first one, curious if there's any meaningful contribution from lymphoma or multiple myeloma volumes embedded in the 2026 framework for Signatera. And just more broadly, how should we think about potential upside from heme MRD lines?

Yeah, that's a great question. So I would say when you look at the model that we just sort of outlined, I would say the contribution is relatively limited, but we think, again, that's a big opportunity for us. If you look at the overall market, the strength with bringing the Foresight team in and just their experience and the amount of data that they generated there, the reputation that they have there, I think it's a big opportunity for us. So again, it's sort of conservative in the model. But when you look at the potential for upside there, I think that could really be one of the growth drivers.

Okay, got it. That's helpful. And maybe just another one follow up for me on Japan. I think you've said in the past, you could see approval for Signatera there in 26 with preliminary coverage to set up a launch in 27. What would this preliminary coverage decision mean for Signatera ASPs and the volume opportunity next year. And curious if coverage would be capped until we see a full readout from Circulate Japan. And then any thoughts on the, you know, build out from a Salesforce perspective in Japan or lab capacity and what that would mean for UPEX? Thank you.

Yeah, so I'll make a couple comments and then maybe John or Solomon, if you guys want to jump in. But, you know, we've already built out a, you know, reasonable-sized sales team there and established a strong distribution partnership. And we're in a position to launch, you know, very soon, you know, when we get the final approval. You know, from an ASP standpoint, you know, we think the ASP is going to be good if you just look at sort of historical precedent. And, you know, I think we're in a great position. You know, Obviously, we've generated some incredible data in Japan. The test is sort of already baked into the guidelines. So I think we're in a great position to generate a lot of volume and revenue as we look into 2027. You know, I think throughout the calendar year 27 and, you know, finishing 27, Japan is going to be making a very, very solid impact on our revenue.

Yeah, just to build on what Steve said, there's more to similar amount of patients with colorectal cancer in Japan than the U.S., despite the smaller population. When you look at similar molecular genetic products, you see pricing highly similar to the U.S. We do not need to wait for the end of Circulate to launch or rather to read out your referencing. and we're in the final stages now with the regulatory authorities there and looking forward to a big launch later this year.

Awesome. Thanks, guys.

Your next question comes from the line of Shubu Nambi with Guggenheim. Please go ahead.

Hi, this is Ricky on for Shubu. Thanks for taking our questions. Wondering what you saw with respect to market share changes in the women's health market in 2025 and then what your guidance and some of the volume comments you made for women's health is assuming with respect to further market share gains?

Yeah, it's a great question. So, you know, we don't really have data on, you know, what everybody else is doing in women's health, but I can say from, you know, for us, we had a record year. We, you know, we did very, very well in women's health and we're off to a great start in Q1. And I think all of that was done, you know, really without having the 21 gene fetal focus test, which we now have. And we're seeing that physicians like it. And it's given us an opportunity to go close new customers that, you know, previously we haven't had access to. And I think it's a good opportunity for us. So, you know, we don't really know exactly about others' share, but I can say, you know, for us, you know, we're growing our business, and we're seeing record numbers.

Your next question comes from the line of Dan Leonard with UBS. Please go ahead.

Thank you very much. I'm wondering how you're framing the opportunity around higher sensitivity for Signatera. You now have a couple shots on goal there between Signatera genome, which you haven't talked about in a while, and now the phase variant product as well. So just help me provide some better, you know, framing or context around what the opportunity looks like there.

Yeah, so, you know, certainly I think on today's call, we kind of mentioned, you know, the phase variant approach getting down below one part per 10 million in LOD studies. And we think that that is like incredibly strong performance. You know, if you look at, I think, the published analytical validations, I think that that performs very, very well. You know, what we're doing is we're trying to give the best product possible to positions and backing that with very strong data. And so, you know, we have the exome MRD test, which works very, very well. We think has shown incredible performance when you look across the studies. Then, for those who want a genome-based test, we're making that available as well. We announced at JPMorgan that we're versioning the genome-based offering, and that's going to now include phased and structural variants, and that's going to be launching soon. So I think we really will have gold-plated MRD offering for those that want that. And then on the other hand, we have, you know, highly published, highly tested, reliable MRD product with significant numbers of outcomes data with the Signatera Exome product. And that's setting up like an incredibly competitive positioning for us. And we've also augmented that with the Latitude Tumor Naive MRD. Now, of course, there's competition, you know, but we think we're in a good position. we've put ourselves in a great spot by generating a lot of data and innovating and investing in research and development to continue to lead the pack.

Appreciate all that. And then just on the topic of SG&A, can you help me better understand how you're able to keep SG&A flat in 2026 yet still grow revenue? I think it was at a pro forma clip of 26%. What's making the the sales force more efficient.

Yeah. You know, Mike, do you want to comment on that?

Sure. I mean, I think it's just, I mean, we've wanted to grow our way to the next level for some, you know, potential breaking in and now we're going to get closer to the profitability, not by making cuts, but by making investments and growing the top line. So we did that in spades. In 25, we've built up the commercial teams really across the board, but with a particular concentration in oncology, those teams are ready to go, and they're in position to drive a lot more top line than they have to date just because they've been new and they're coalescing. So I think it's a good case study in how we can drive leverage in the business. And not to say that we won't make, like I said in the prepared remarks, we won't make opportunistic investments, not to say that things won't come up that we think are worthy uses of capital. But I think it underlines our kind of core strategy over time.

Thank you very much.

Your next question comes from the line of David Westenberg with Piper Sandler. Please go ahead.

Hi, thanks for taking the question. How should we think about how MoldyX is going to think about histology types for latitude? Basically, what I'm kind of asking here is how can you use your infrastructure and learning to kind of feed that process and coverage? And how is ADLT going to work? As you know, you have full genome, latitude, all those kind of things. Is there a way to tuck it in or, you know, is it just completely different? There's no possible way. And how should we think about reimbursing period?

Yeah, that's a good question. So, you know, we think the, you know, we're not planning to submit for an ADLT for latitude just based on, you know, the fact that there's other tumor-naive MRD tests on the market and there's other MRD tests. So, we don't think tumor-naive are eligible for an ADLT. And I think that we, you know, we've kind of said that previously without getting FDA approval. But, you know, when we look at other tumor-naive MRD products and how they've been priced, you know, we think that that's sort of well-established and we'll be able to kind of get similar pricing. So, you know, we've submitted for CRC as we launch other products in the future. We're going to generate and publish validation data for those and then submit for those as well. there's not really a shortcut process. You know, you have to, you know, generate the data and, you know, publish it and submit it. And luckily for us, you know, we started this back in, you know, 2015 trying to generate data. And, you know, so we have kind of 10 years now of data that we can rely on, and in some cases, we have biobanks or samples we can go back to and rerun when we're looking at the Latitude product, and I think that's going to help us get moving very quickly.

Thanks. A quick follow-up for Mike, how are you thinking about the ROI on some of these R&D investments? You mentioned on the call technology advancement for MRD. Can you kind of just explain what that means, and are there any, in your mind, NCCN-generating studies that could be coming out soon and tissue types other than CRC and muscle-invasive fatty cancer. Obviously, I don't mean soon, like next six months. I kind of mean like two years, three years, but thanks.

Yeah, I mean, kind of the basic components of how I think about returns to capital invested on R&D generally. I mean, Signature is a great case study is just, hey, what is the TAM and what is the potential for incremental both volume growth and pricing growth. And the R&D really hits on both of those metrics. I mean, in terms of the volume growth, when you have a study that's in the New England Journal that's like a landmark study in multivisive bladder cancer, that drives a lot of incremental volume. Over time, we hope that it can also kind of drive guideline inclusion. So, the volumes at what is already a high-margin product drive very clear ROICs. And then the data that ultimately gets you into guidelines drives the ASPs much higher than they are right now. So, if you just recall, I mean, when we get paid, we get paid something like $3,000 per test. The ASPs, as we've been talking about, are in that kind of 12-20 range, right? So, the delta there is just kind of non-covered tests. And the way that you get there is investment in more clinical trials, more evolution of the product. And you can get really comfortable with the ROCs because you see these volumes, right? Like these volumes are repeat volumes. You get very comfortable that we can have very rapid volume growth. So any investment that drives incremental realized pricing per test, it's easy to see where the ROCs come from there. Thank you guys.

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

Please go ahead. Great. Thank you for taking the question. Just one quick one. On the OPEX guide, it's nice to see the operating leverage should really start to turn on in 2026, but it sounds like you're leaving yourself some freedom to spend more should it make sense, and you see an opportunity with the ability to fuel future growth. I guess, how do you define the threshold of what makes sense to spend on in excess of Because I'm sure there's no shortage of opportunities that could fuel future growth.

Yeah, look, I mean, it comes back to the question that David just asked. I mean, it really just comes down to ROICs. I mean, whether that's a, you know, small acquisition like what we did with Foresight or, you know, internal projects. We take each project with kind of an ROIC framework. And, you know, I'm still the newcomer on the management team on the phone here. I mean, this is year 11 for me and all these other guys. Each one of these guys has been here longer than me. So we've got a very long time together evaluating all of these different opportunities and then trying just to rank each one and understand there's a risk benefit, there's an execution challenge associated with each one, and we just try to make the right decision kind of based on what the right returns are and what's best for the patients.

And ladies and gentlemen, that's all the time we had today for questions. This does conclude today's conference call. Thank you for your participation, and you may now disconnect.