Earnings Call
Natera, Inc. (NTRA)
Earnings Call Transcript - NTRA Q4 2025
Operator, Operator
Welcome to Natera's 2025 Fourth Quarter Financial Results Conference Call. 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.
Mike Brophy, CFO
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 Moshkevich, President, Clinical Diagnostics; Alexey Aleshin, General Manager of Oncology and our Chief Medical Officer; and John Fesko, 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.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 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 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 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. Natera 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?
Steve Chapman, CEO
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% compared to Q4 of 2024. We generated roughly $666 million in revenue in the quarter, which is about $6 million ahead of our preannounced 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 preannounced 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 double 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 and $2.7 billion in revenues, gross margins between 63% and 65%, holding SG&A 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 MolDx and launching the 21-gene Fetal Focus 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 Signatera and the Latitude MRD test, both of which complement Signatera beautifully. We delivered the strongest year yet for Signatera data generation, highlighted by the IMvigor011 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 and is already paying dividends as we'll discuss today. We also advanced 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 transplant. 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 Signatera 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 strength 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 preannounced on very strong overall volume growth and another quarter of sequential improvement in ASPs. We had an excellent oncology quarter and continued to see strength in women's health and organ health. Signatera ASPs stepped up to roughly $1,225 in Q4. We had about $60 million in true-up this quarter, consistent with our preannounced as cash collections continue 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%, and we had about 3% of that benefiting from the revenue true-ups. Stripping out the true-ups, we posted a record organic gross margin quarter at 63.7%. 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 in 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 online 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?
Solomon Moshkevich, President, Clinical Diagnostics
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 LinkedSNP 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 NIPT product in the market with impressive flexibility as it can either be ordered upfront 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 OB/GYN 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 improving 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 occurs monthly or even more in year 1 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 1 month after transplant to surveillance either with Prospera or with EMB in a 2:1 ratio with clinical 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 Prospera-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 forgo the nine-month surveillance 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 it 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?
Alexey Aleshin, Chief Medical Officer
Thanks, Solomon. Here, we're highlighting what we view as exceptional momentum in bladder cancer going into the ASCO GU conference. At a single meeting alone, we have 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 INDIBLADE 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 ASCO GU 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 in frontline recurrent or metastatic head and neck squamous cell carcinoma. What makes SYNERGY especially important is that it's not just showing ctDNA is prognostic, it demonstrates the benefit of CTA-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, starting with immunotherapy alone and risking undertreating patients who need a rapid cytoreduction, or starting with immune therapy plus chemotherapy and risking overtreating patients who may not need prolonged chemotherapy exposure. The question is whether we can achieve the best of both worlds using Signatera-guided adaptive treatment approaches. In the study, patients started on either pembrolizumab alone or pembrolizumab plus chemotherapy. And then Signatera ctDNA dynamics were used to escalate or deescalate chemotherapy in real time. The first important result is that 74% of patients deescalated a chemotherapy at least once with a 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. Importantly, the rate of grade 3 or higher toxicity was only 48%, which is a clear improvement over historical precedents. The punchline is that SYNERGY supports a future where Signatera 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 MolDX 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 on our MolDx submission and our face variant technology. John?
John Fesko, President, Chief Business Officer
Thanks, Alex. I'm excited to announce that Natera has submitted our first tissue-free MRD assay to MolDX 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 data set 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 year. 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 Signatera 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 Signatera 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 variant takes 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 variants 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 variants, the probability that such errors identically replicate multiple variants on a single fragment is so low as to be almost 0. 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 3 parts per 10 million and detection below 1 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. Mike?
Mike Brophy, CFO
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 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-time deferred tax item related to the Foresight acquisition. We think our path to 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 $1 billion 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 2026, but I expect true-ups as a percent of revenue to decline as we continue to ring 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 and 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 gains. 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 organ 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 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 guys discussed 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 midpoint, 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-sized 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 DEFINE trial for early cancer detection in colorectal cancer and the investments we are making in large clinical trials and technology development focused 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.
Steve Chapman, CEO
Thanks, Mike. In summary, we had a great year across the business. And as you can see on the slide, we have several exciting milestones anticipated as we move through 2026. Okay. And with that, let me open it up to questions. Operator?
Operator, Operator
Your first question comes from the line of Catherine Schulte with Baird.
Catherine Ramsey, Analyst
Maybe first, just on Signatera 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?
Steve Chapman, CEO
Yes. Thanks, Catherine. Mike, do you want to take that?
Mike Brophy, CFO
Yes, thank you, Catherine, for the question. The changes on the ADLT rate and the bundle largely offset each other, considering the mix we've had regarding recurrence and bundles over the past year. The Net 30 reflects our ongoing efforts to increase the proportion of time we are reimbursed for covered services related to Medicare Advantage volumes and our advancements in the biomarker states. There remains potential for further improvement with additional coverage decisions and the initiatives we are pursuing with MolDX, as John Fesko discussed. Over the past 10 to 11 years, our strategy with these initial guides has been to begin with a challenging but attainable baseline for the year, which is how I would describe this ASP guide.
Catherine Ramsey, Analyst
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 for MolDx, I guess, what would that mean for ASPs?
Steve Chapman, CEO
Yes, I'll take that. So yes, I think we've kind of said before, obviously, CRC, breast, bladder, lung, some of the bigger ones there that we're already covered for making up the majority. But there's a good 30%, maybe 35%, something in that range that fall into kind of the non-covered bucket. That's kind of where we said if we can get coverage for the remaining Medicare indications, it could be based on the run rate, a couple of hundred million dollars in gross profit and revenue. And we submitted now for a significant number of additional indications that would, I think, capture the vast majority of the remaining outstanding histologies. And we have a good track record of getting Medicare coverage just given the significant amount of data that we've generated. So hopefully, that remains as upside on the ASP, as Mike said.
Operator, Operator
Your next question comes from the line of Puneet Souda with Leerink Partners.
Puneet Souda, Analyst
First one, maybe just given the strong growth in Signatera that you're seeing here, despite the seasonality, despite the holidays, you put up a very strong number. Last year, you were talking about sequential 8,000 to 10,000 increases. Mike, maybe for you, 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 sort of needle moving this year in terms of the data? And any thoughts on NCCN? And just I have a follow-up on prenatal.
Steve Chapman, CEO
Yes. So maybe let me comment just for a second on some of the data and then 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 in a broader set of indications. And I think you're starting to see a lot of that come out. So we just had this interventional trial in head and neck cancer, which we think is a great indication. I think there's about 70,000 patients per year there. 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 we're now generating the type of data in these other indications that 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 we talk about the pacing?
Alexey Aleshin, Chief Medical Officer
I think that's pretty good summary. I think, Puneet, if you just look at ASCO GU this year, I was actually at the conference earlier today, had a ton of excitement, probably three or four pretty practice-changing studies that we commented on during the pre-read. And 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 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.
Mike Brophy, CFO
Yes. Just on the pacing, I have the same perspective as before regarding the approach. I believe the best way to project the growth of the Signatera units is to use the average from the last four quarters for the sequential growth. That was around 19,500 units last quarter. If you do the math with the Q4 number, it seems to reach about 20,000 units, which I think is a reasonable expectation for Q1. This approach is beneficial because it updates itself, reflecting the compounding effect we see in the business, considering the repeat volumes per patient. Therefore, I anticipate that this base expectation will continue to rise. The average over the last four quarters helps to smooth out any random fluctuations that might occur from quarter to quarter due to factors like the number of days, holidays, or similar issues. So, I believe this is the right method, and it will keep increasing as the business continues to perform better.
Puneet Souda, Analyst
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 of a single assay. You have two assays here. So maybe just walk us through the patient workup conversation, marketing of this assay? And 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?
Steve Chapman, CEO
Yes, I'll respond to that. The key question is whether physicians appreciate the product. From our observations, there is considerable interest in the fetal focus test, and we believe we are meeting all the necessary criteria. The volume is increasing, and we expect this trend to continue throughout the year. In terms of marketing, our test operates similarly to other single gene tests available, particularly regarding how it is ordered and the flexibility it provides. You can choose to order the test upfront; if the mother tests positive, the Fetal Focus test will be conducted, similar to how competitors handle it. You need to confirm the mother's positive status before running the fetal test. Additionally, you have the option to order the test, send in the blood sample, and wait to determine if the mother is positive, at which point we can proceed accordingly. We provide various approaches, ensuring flexibility for how clients can access the test. We're observing a significant increase in interest. The selection for the SMFM plenary presentation is a prestigious honor that we are very excited about and highlights the strength of our data.
Operator, Operator
Your next question comes from the line of Dan Brennan with TD Cowen.
Dan Brennan, Analyst
Can you provide some insight on Signatera as we exited 2025? I understand there was a question about pan-cancer, but could you discuss the types of tumors and what you identify as the main drivers? As we approach 2026 and anticipate continued growth in Signatera, are you observing any key trends? We know IMvigor is impacting bladder cancer, but what other trends are you noticing in the overall landscape? I'd like to get a sense of the current situation in the field.
Steve Chapman, CEO
When considering various tumor types, there's significant activity across the board. The data released over recent years has shown a lot of momentum, particularly with IMvigor in bladder cancer. The recent findings mentioned at ASCO GU regarding bladder preservation are likely to create considerable excitement. As physicians become familiar with the product, they often start using it in one tumor type and then branch out as they see positive data for others. This means they might begin with a specific category of patients and, upon seeing favorable data, expand their use within that tumor type. This collective knowledge is driving growth. It’s not solely due to one factor; rather, it's a combination of over 100 peer-reviewed papers, a strong commercial and medical affairs team, and widespread product adoption, with more than half of doctors now ordering it. Continuous investment in new clinical trials and the expansion of the product portfolio with Signatera genome and Latitude is also key.
Dan Brennan, Analyst
Okay. Great. Maybe just on one outside of Signatera, 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?
Mike Brophy, CFO
Yes, absolutely. For Prospera's organ health products, I believe they will continue to grow along a long-term upward trend. We saw over 50% growth in 2025, and I anticipate another strong year for Organ Health this year. This growth is largely driven by the market's evolution and the increasing importance of cell-free DNA in patient care. Regarding women's health, as Steve mentioned, we have had an excellent start. The first quarter is typically our most significant, and I expect mid-single-digit volume growth for women's health. I believe revenues could surpass that due to our ability to achieve pricing gains like we have in previous years. Let me pause there to see if Steve wants to add anything or provide further comparison.
Operator, Operator
Your next question comes from the line of Doug Schenkel with Wolfe Research.
Douglas Schenkel, Analyst
I think this is a follow-up to Catherine's earlier question, and I apologize if I misunderstood the response. Could you provide the breakdown of Signatera volume and mix between exome, genome, and Latitude for the fourth quarter? How are you considering the mix in 2026, and how does that impact potential upside and downside scenarios for gross margin? Additionally, is it reasonable to expect that CRC will fall below 50% of total Signatera and Latitude volume as indications like breast and lung continue to grow and gain traction this year?
Steve Chapman, CEO
Yes. Good question. So yes, I'd say on CRC, certainly, we think over time, things will sort of normalize to meet roughly kind of what you would see in the marketplace from the standpoint of cancer prevalence. I mean obviously, breast is going to be the largest over time. And so I think CRC will normalize, but it's still driving 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, some of the other tumor types are really starting to accelerate. And I think that's great for us because we've spent the last eight years generating data in these other tumor categories. And now some of that data, like this head and neck 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 those that are interested in that. We've sort of built in an increase over time there, and that's part of our existing model. And then from a Latitude standpoint, I think the initial kind of idea there was there's a small portion of cases, maybe 5% or something in that range where we're not getting the - we're not able to get the tissue in CRC. And in those cases, we can now serve those patients for Latitude. But there's also another opportunity, which is just the sort of physicians who just want tumor naive. And 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.
Operator, Operator
Your next question comes from the line of Casey Woodring with JPMorgan.
Casey Woodring, Analyst
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 volumes?
Steve Chapman, CEO
Yes, it'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, now the strength with bringing the Foresight team in and just their experience and the amount of data that they've generated there and 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.
Casey Woodring, Analyst
Okay, got it. That's helpful. And then 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 build-out from a sales force perspective in Japan or lab capacity and what that would mean for OpEx?
Steve Chapman, CEO
Yes. So I'll make a couple of comments and then maybe John or Solomon, if you guys want to jump in. But we've already built out a reasonable sized sales team there and established a strong distribution partnership. And we're in a position to launch very soon when we get the final approval. From an ASP standpoint, we think the ASP is going to be good if you just look at sort of historical precedent. And I think we're in a great position. Obviously, we 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. I think throughout the calendar year '27 and finishing '27, Japan is going to be making a very solid impact on our revenue.
John Fesko, President, Chief Business Officer
Yes. Just to build on what Steve said, there's more to similar amount of patients with colorectal cancer in Japan than U.S. despite the smaller population. And 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 the readout you're referencing, and we're in the final stages now with the regulatory authorities there and looking forward to a big launch later this year.
Operator, Operator
Your next question comes from the line of Subbu Nambi with Guggenheim.
Unknown Analyst, Analyst
This is Ricky on for Subbu. 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?
Steve Chapman, CEO
Yes, it's a great question. We don't have data on what others are doing in women's health, but I can say we had a record year and performed very well in that area. We're off to a great start in Q1 as well. This success was achieved even before we introduced the 21-gene Fetal Focus test, which we now have. Physicians are responding positively to it, and it's allowing us to connect with new customers we hadn't accessed before. This presents a good opportunity for us. While we don't know the specifics about others’ market shares, I can confidently say that we are growing our business and achieving record numbers.
Operator, Operator
Your next question comes from the line of Dan Leonard with UBS.
Daniel Leonard, Analyst
I'm wondering how you're framing the opportunity around higher sensitivity for Signatera. You now have a couple of 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 framing or context around what the opportunity looks like there.
Steve Chapman, CEO
Yes, we discussed the phase variant approach achieving less than 1 part per 10 million in LOD studies, which indicates remarkable performance. The published analytical validations support this strong showing. Our goal is to provide the best possible product to physicians, backed by solid data. We have the exome MRD test, which demonstrates excellent performance across various studies. Additionally, for those interested in a genome-based test, we are updating our offering to include phased and structural variants, which will be launching soon. We believe this will create a premium MRD option for those who seek it. On the other hand, we have a well-published and reliable MRD product, the Signatera exome, with substantial outcomes data. This positions us competitively in the market. We've also enhanced our offerings with the Latitude tumor-naive MRD. While we acknowledge the competition, we feel confident in our position due to the data we've generated and our ongoing commitment to innovation and research development.
Daniel Leonard, Analyst
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 sales force more efficient?
Steve Chapman, CEO
Mike, do you want to comment on that?
Mike Brophy, CFO
Certainly. We aimed to achieve growth towards profitability not by reducing expenses but by making strategic investments and increasing our revenue. In 2025, we significantly expanded our commercial teams, especially in oncology, and they are now positioned to generate much higher revenue than before as they are coming together. This demonstrates how we can leverage our business effectively. That said, we are open to making strategic investments when worthwhile opportunities arise, but this approach reinforces our long-term strategy.
Operator, Operator
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.