Operator
Welcome to Natera's 2035 Third 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 question-and-answer session. To ask a question at that time, please press star followed by one on your touchstone phone. If anyone has difficulty hearing the conference, please press star zero for operator assistance. As a reminder, this conference call is being recorded today, November 6, 2035. I would now like to turn the conference call over to Michael Brophy, Chief Financial Officer. Please go ahead.
Thanks, Operator. Good afternoon. Thank you for joining our conference call to discuss the results of our third quarter of 2025. On the line, I'm joined by Steve Chapman, our CEO, Solomon Moskovich, President of Clinical Diagnostics, and Alex Alessian, General Manager of Oncology, and our Chief Medical Officer. Today's conference call is being broadcast live via webcast. We will be referring to a slide presentation that has been posted to investor.natera.com. A replay of the call will also be posted to our IR site as soon as it's available. Starting on slide two, during the course of this conference call, we will make forward-looking statements regarding future events and our anticipated future performance, such as our operational and financial outlook and projections, our assumptions for the 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 are contained in or suggested by the forward-looking statements. Forward-looking statements made during the call are being made as of today, November 6, 2025. If this call is replayed or reviewed after today, the information presented during the call may not contain current or accurate information. The narrative claims 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-and-year comparison. And now I'd like to turn the call over to Steve. Steve?
Thanks, Mike. Let's get to the highlights on the next slide. We had a fantastic quarter. We generated $592 million in revenue, which is up about 35% over Q3 of last year. We had an excellent volume quarter as well, which included strong growth across the product portfolio and another record for Signatera growth. We processed 202,000 clinical MRD tests in the quarter, which represents more than 21,500 units of growth compared to the second quarter. You'll recall that we had a record of 20,000 Signatera growth units in Q2, so we're very pleased to beat that record again in Q3. Gross margin took a big step up in Q3, coming in at 64.9%, which is almost 1.5 percentage points higher than we were just last quarter. Ex-true ups, gross margins grew over a full percentage point versus Q2 and almost three percentage points over Q3 of last year. Given all that momentum, we are in a position to significantly increased the 2025 financial guide. We are raising the revenue guidance by 160 million at the midpoint and now expect revenues in the range of 2.18 billion to 2.26 billion, which is a full reset of the prior revenue range. We are raising the gross margin guide to 62 to 64 percent in recognition of the gross margin performance we saw in the first three quarters and AFP and COGS momentum continuing in the business. We are also modestly bumping OPEX guidance, which is largely from the one-time expenses that have accumulated over the course of the year that now total around $60 million. In addition to those one-time expenses, there's a small increase in R&D to support Molde-X coverage for the remaining signatory indications. Based on this effort, I'm excited to announce we are now in a position to submit seven new Molde-X submissions before the end of the year this year which we've said can be worth around 250 to 300 million dollars of gross profit based on our run rate we've also invested to expand the market by increasing the number of definitive mrd trials and to support the fda enabling fine study for early cancer detection it's important to note that our sgna was flat to down between q2 and q3 which is aligned with what we said about pre-spending to build the commercial team in the first half of the year. We aren't planning any big commercial expansions anytime soon, and we'll talk a little bit more about that later in the call. Finally, on guidance, we are substantially raising our guide for free cash flow generation for the year, where we are now formally expecting to generate roughly $100 million in cash for the full year. Of course, we were thrilled to see the signature care data readout from the InVigor 011 trial in bladder cancer, and we appreciate Dr. Tom Poles for joining us on the special call we held a few weeks ago to review the results. We think the InVigor trial results represent a fundamental new paradigm in cancer care enabled by Signatera, and that data has been published now in the New England Journal of Medicine. Finally, we touched on our last call that we were very excited to launch Fetal Focus, a new single-gene NIPT for inherited conditions that leverages our proprietary SNP-based method. We recently announced an expansion of the fetal focus product to cover over 20 genes planned for this quarter. The initial feedback from our August launch is positive, and we think this is a compelling expansion of the panel. Okay, let's get into some of the business trends on the next slide. The first slide shows our Q3 volume progression versus prior years. We had solid sequential quarterly growth in women's health driven in part by interest in fetal focus that spurred a lot of new commercial activity for our team. Oregon Health was also very strong with both Greenfield and competitive wins, and we will continue to keep our foot on the gas as we have several clinical trials ongoing that further demonstrate how much utility and cost savings these tests are delivering. Of course, Signaterra posted another record quarter, which we'll get into on the next slide. Overall, the volume momentum in Q3 was very strong across the products and then has continued into Q4 thus far. The next slide shows our clinical MRD unit growth over time. We had another record growth of 21,500 additional units, which includes more than 21,000 Signatera growth units and a few hundred latitude growth units. As a reminder, we offer latitude as a reflex to Signatera when Signatera can't be performed. This unit growth represents 56% year-on-year growth versus Q3 of last year, and this is the fastest year-on-year growth rate we've had in all of 2025. The drivers here are really the same as we covered on prior falls. Groundbreaking clinical data combined with excellent customer experience. New patient starts were again strong as physicians continue to use the test for ongoing monitoring. We see adoption being fueled by the excellent data released earlier this year, including at ASCO, ASCOGI, and ESMO. We haven't had time yet to see the effect of the recent ESMO data or the publication in the New England Journal of Medicine, but clearly those are both very positive factors. We'll talk more about the implication of these results later in the call. The mix of tumor types we're seeing continues to be broad-based as physicians really start to generalize the use of Cignatara in their clinics. That broad adoption drives volume growth, but also creates a large revenue opportunity as we broaden the range of tumor types that we can get reimbursed. The next slide shows revenue, which was another area of significant outperformance this quarter. We grew revenues 35% over last year, which is actually faster than Q2, despite the tough comparable. This was from strong volume performance combined with excellent progress on ASPs. Each of our major products had a sequential improvement in ASP in Q3 compared to Q2. Women's Health and Organ Health each had another standout quarter, and signatory ASPs are now at roughly $1,200. We had about $55 million in true ups this quarter as cash collections continued to accelerate, and we posted another record for DSOs at 49 days, compared to 57 days just in Q2. That trend is continuing in Q4, as October was a clear new record for cash collections. All of this bodes well for future AST growth, as Mike will describe later in the call. The next slide shows our gross margin traction over time, and we posted another strong gross margin quarter in Q3. Top-line gross margins were a record as we got very close to that 65% level. Stripping off the revenue true ups, we grew gross margins a full percentage point to 61.3%, just compared to Q2. We drove that with a combination of better ASPs as well as COGS, which were also very lean in the quarter across the board. In addition to COGS efficiencies, we spent some time on our last call talking about the other key margin expansion vectors we're pursuing. Investing in revenue cycle operations has been a huge win for us over the last two years. and we are now at a level where we think we can hold that dollar spending steady as we continue to grow ASPs, which gives us leverage on the prior investments. I also mentioned the coverage expansion opportunity that was really across the board, but particularly in Signatera. In addition to getting more tumor types covered by Medicare, we are starting to see some green shoots in biomarker state reimbursement for commercial volumes. We estimate the growth in Signatera ASP this quarter was driven primarily by the success we had in the spring and fall working with health plans in these states to cover Signatera for their patients. I think that's going to be a pretty steady linear process for us over the next two years or so. Finally, all of the above can be accelerated with the deployment of AI. In addition to driving innovation, for example with our foundation models, AI is already helping us scale these operations as volumes grow without forcing a commensurate increase in headcount. Okay, that's a good segue to the next slide on OPEX. We went into some detail on the last call describing the investments we were making this year in both R&D and commercial operations to extend our leadership in MRD. Looking at Q3, this R&D increase reflects the investments we made to support multiple new product launches, as well as the expansion of our clinical trial and data generation efforts for both Signatera and early cancer detection. This year, we've launched Signatera Genome, Latitude Tissue-Free MRD, fetal-focused single-gene NIPT, and we're about to launch this expanded version of fetal focus. All of these things put us in a position to keep doing well in the market and to continue helping millions of patients per year. In clinical trials, as I mentioned, we're doubling down on evidence generation and that investment we've been making has really paid off we are now in a position to submit seven new multi-ex submissions by the end of the year and as i mentioned earlier in the call reimbursement for all the remaining indications could be worth around 250 to 300 million dollars of gross profit based on a run rate so this is well worth the investment in addition we're launching many interventional trials to continue advancing the field towards incorporating personalized MRD into the standard of care. In addition to Signatera, the advanced adenoma data we now have in hand gives us a lot of confidence to push as fast as we can to get a high-quality result in the FDA-enabling FINE trial, which is already enrolling. This is a big investment, but we think it's worth it given the very attractive opportunity at ECD that includes a large market size high gross margins and a very strong performance for our technology we'll get into more detail in that effort a little bit later today finally as you can see here on the slide our sgna is slightly down sequentially from q2 to q3 that largely reflects the fact that we're now in a very good spot with a commercial team and with our revenue cycle operations which were big areas of sgna investment in the past we're now in a position to drive significant scale from these prior investments. As we start to look out to next year, we expect there will be limited OPEX growth of roughly 10%, while revenues grow much faster and margins continue to improve. The OPEX investment will be focused on executing definitive Signicare clinical trials to expand the market and completing the FDA-enabling FIND ETD study, where we will be enrolling patients in 2026. As we said before, we think these are both very smart investments. Okay, with that, let me turn it over to Solomon to discuss more details. Solomon?
Thanks, Steve. Getting into some of our new data and announcements, I want to start with the expansion of our fetal focus test. We originally launched fetal focus in August, with a panel covering five of the most common inherited conditions.
CF, SMA, Fragile X, alpha thalassemia, and beta hemoglobinopathies, including sickle cell anemia.
The goal of the test is to offer a solution for pregnant mothers who are carriers of one of those inherited genes, but where the father is unavailable for screening to see if the baby might be at increased risk. In these cases, with a simple blood draw, our fetal focus test can directly assess the fetal DNA circulating in the mother's blood to detect potential fetal inheritance from both mother and father. This can be done with high sensitivity and specificity, and we believe it is the next best thing when DAD is not available for screening. So the news from last week is that we are expanding the panel to cover 20 of the most common genes and launching that before the end of this year. The validation of this expanded panel, like the original 5-gene panel, leverages prospectively collected samples from the EXPAND trial, which has enrolled over 1,700 high-risk pregnancies from a diverse multi-ethnic population, where those pregnancies include those with dual inheritance from both parents, partial inheritance from one of the parents, or zero inheritance, and confirmed fetal outcomes in all cases based on prenatal or postnatal diagnosis. Testing and confirming all negatives in particular is critical for a robust estimate of test sensitivity. We use our proprietary linked SNP technology to improve detection of challenges homozygous cases, which is where both parents are carrying the exact same mutation in a given gene. This happens with regularity in certain conditions, like the classic Delta F508 mutation, which causes cystic fibrosis, if inherited from both parents. Linked SNP uses information about neighboring DNA loci to work out likely inheritance patterns. We are pleased with the response from the medical community after our initial launch in August, and we know folks are looking forward to this panel expansion so that our Horizon customers can interrogate the cell-free DNA for a broader set of potential inherited conditions. Turning now to oncology, where we had a strong quarter of clinical adoption and new evidence generation. At the ESMO conference, we had 14 abstracts, including six orals, with a blockbuster readout in muscle-invasive bladder cancer across two different studies, Vigor011 and Checkmate274. both of which also had concurrent publications in the New England Journal of Medicine and Annals of Oncology, respectively. Many of you tuned in after the conference for our special call with Professor Tom Pold, Director of the Barth Cancer Center in London and Chief Principal Investigator of the Invigor 011 trial, who reviewed the significance and the novelty of this data. For those who could not join that call, the link is on our Investor Relations page. But the summary is that we have generated level 1A evidence to support the role of Signatera in directing treatment after radical cystectomy. As the discussant said during the Congress, this is the strongest evidence to date for intervening with adjuvant systemic therapy on the basis of detecting plasma CT DNA.
There are three more things to note.
Number one, the Invigor 011 protocol called for Signatera monitoring every six weeks after surgery. This is a serial surveillance protocol, not simply a one-time test. Number two, patients who tested positive with Signatera at any time in that first year after surgery derived significant benefit from immunotherapy, improving overall survival by 41%, while patients who remained negative derived no treatment benefit and had excellent outcomes with no treatment at all, achieving 97% overall survival at 24 months. Number three, the result was consistent across cohorts, InVigor011 with atezolizumab and Checkmate274 with nivolumab. Antigatera is expected to have a role in post-surgical care regardless of the neoadjuvant treatment regimen. As perioperative care is expected to grow in popularity, which is treatment both before and after surgery, questions will always remain about which patients benefit the most from additional systemic therapy after surgery, which can often be hard for patients to tolerate. As a reminder, the median age of diagnosis in the U.S. for muscle-invasive bladder cancer is 73 years old. Ultimately, each doctor and patient will have to make their own informed decisions, and now they can look to Signatera MRD status for additional guidance. We expect this data to fuel adoption of Signatera among GU oncologists and to have a positive halo effect on the overall field and further to differentiate Signatera. Among the other readouts at ESMO, the colorectal data was also notable. Data from the INTERCEPT study and the NICHE study were presented. Those showed that Signatera dynamics, and particularly MRD clearance during or after therapy, were reliable markers of therapy response. In the INTERCEPT study, they followed ctDNA patterns from over 1,300 colorectal cancer patients. showing the rates of clearance after adjuvant therapy and what it meant. In this cohort, adjuvant therapy achieved MRD clearance in approximately one-quarter of the patients who had tested positive after surgery. And it was very rare for a clearance to occur spontaneously, without treatment only 2% to 4% of the time. This makes Signatera extremely reliable for evaluating response to adjuvant therapy. In the NICHE study, published concurrently in the journal Nature, the investigators conducted an in-depth analysis of response to neoadjuvant immunotherapy in patients with MMR-proficient colon cancer. While they identified novel predictive signatures based on TP53 status, immune cell proliferation, and whole genome duplication, the study also showed the power of signatera dynamics to predict response. Out of the six patients who achieved response based on pathologist's review of their resected tumor, five out of six had cleared their ctDNA prior to surgery. And out of the 20 patients who failed to achieve pathological response, 19 out of 20 were still ctDNA positive prior to surgery. This all points toward the clinical utility of using signatory in the neoadjuvant setting to inform the surgical and adjuvant treatment plan. Both of these studies together, with similar evidence in other cancer types, all tell a growing story of Signatera supporting a new type of surrogate endpoint to hopefully accelerate future drug approvals as well. While Signatera had a successful showing at ESMO, there were other ctDNA-guided trials using other assays that did not hit their endpoints, for example, in colorectal cancer and lung cancer. We believe this underscores the differences between ctDNA assays and technologies, as well as differences in trial designs. As several presenters noted explicitly during the OSMO conference, study results are not necessarily transferable between ctDNA assays. The field is coming to appreciate that there can be significant differences in performance between different technologies. It is not enough to measure simply analytical assay performance using controlled mixture experiments in a research lab. It is critical that assays be rigorously evaluated in well-designed, prospective clinical studies, especially when they're going to inform life-and-death treatment decisions. As a reminder, Signatera is unique in that we use a patented multiplex PCR amplification technique, followed by next-gen sequencing, which identifies a targeted set of clonal mutations with the lowest background error rates and sequencing the plasma at extreme depths with over 100,000 reads per target. By contrast, other labs may use hybrid capture techniques that are broad and shallow, tracking hundreds or even thousands of mutations, but sequencing them at shallow depth. Test performance is based on more than the number of targets. We see this over and over again. It depends on the chemistry, the variant selection, and the calling algorithms. All of this helps solidify Signatera's role in cancer care. It will also give rise to a new wave of clinical trials, treating patients only on molecular recurrence and using signatory dynamics to evaluate treatment response. With that, I want to turn over to Alex to discuss our exciting roadmap in early cancer detection. Alex?
Thanks, Solomon. Colorectal cancer is both common and highly preventable when detected early, before or right as the cancer develops. Traditional screening works, but participation is uneven. That's why there's intense interest in accurate, convenient blood-based screening options. We have leveraged our experience at over 250,000 early-stage tumors sequenced to date to drive deep discovery in order to find a proprietary set of markers that differentiate colorectal cancer and precancerous advanced adenomal lesions from healthy controls. We estimate that the vast majority of these markers are currently non-discoverable if only publicly available data sets are utilized. Furthermore, we have embraced an advanced adenoma-first approach, focusing our discovery and algorithm development in order to prioritize performance in the difficult-to-detect advanced adenoma lesions. Lastly, we have invested considerable resources to optimize our methylation technology platform to maximize molecular recovery and prevent signal degradation. Taken together, this allows us to detect signals significantly below 0.01% VAT, a range that is required to improve advanced adenoma sensitivity. Proceed CRC is a U.S. prospective study of approximately 5,000 average risk asymptomatic screening participants who provided blood pre-colonoscopy. In the most recent analysis focused on advanced adenomas that was derived from 1,400 sequential participants with clinical outcomes, we reported a 22.5% sensitivity and a 91.5% specificity. Furthermore, when adjusting performance for histological subtype prevalence in recent FDA-enabling trials, sensitivity remained in the approximate 22 to 24 percent range. This is a step up from earlier 2025 pilot data readout which showed an 18 percent sensitivity at a 91 percent specificity after technological and algorithm refinements. We have heard some questions about if this sample set is representative of the FDA-enabling study. We want to reiterate that these samples were collected in the same fashion and from the same funnels as the FDA enabling FIND study. Furthermore, we know that sample processing occurred in a blinded fashion and the size distribution was potentially more challenging than what we expect in a larger cohort. Before we dive into the data, it's important to understand the types of advanced adenomas that are precursors to colorectal cancer and why their detection is clinically challenging. Advanced adenomas are precancerous polyps that can vary significantly in size, structure, and cellular composition. These include four main subtypes. Number one, the rated adenomas, which are flat and often more difficult to detect visually. Number two, tubular adenomas, the most common but typically smaller and less aggressive subtype. Number three, villus or tubulovillus adenomas, which have a high malignant potential due to greater percentage of villus architecture. And lastly, number four, advanced adenomas with high-grade dysplasia, which represent the highest risk of transformation to colorectal cancer. When looking at adenoma subtype, 78% of lesions in our cohort were serrated or tubular, consistent with the 74% to 78% range observed in other large studies. This alignment indicates that our cohort is representative of real-world advanced adenoma biology, further validating that our results are representative and not driven by an unusually favorable distribution. In addition to histological subtype, detection rates can also vary by lesion size, as smaller or flatter lesions are notably more challenging for blood-based screening methods to detect. In our preceded CRC study, the mean AA size was 13.7 millimeters, notably smaller than the greater than 15 millimeters average reported size in other FDA-enabling studies. Despite the smaller lesion size, which is typically associated with lower detection rates, our results demonstrate promising sensitivity. In summary, the preceded readout underscores Mintera's commitment to advancing early detection through a data-driven approach, our technology showing promising detection rates even under very stringent clinical conditions, laying the groundwork for improved colorectal cancer prevention outcomes. To move from promising readouts to potential screening tests, Nutera has launched Find CRC, an FDA-grade validation study targeting approximately 25,000 average-risk adults who provide blood before colonoscopy, targeting approximately 70 screen-detected CRC cases. Primary aims are CRC sensitivity and specificity in people without advanced precancerous lesions. Secondary aims include performance for advanced precancerous lesions for advanced adenoma. The study is designed to generate regulatory-grade evidence that complements and builds upon perceived CRC development data set. The study has enrolled its first patient in May 2025, and we expect enrollment targets to be met over a cumulative 18-month time frame. With that, let me turn it over to Mike to review the financials. Mike?
Great. Thanks, Alex. The next page is just a summary of the financials compared to last year. We've clearly ramped volumes and revenues while also continuing to transform the gross margin profile of the business. We said a few years ago that long-term gross margins can exceed 70%, and I think the progress we've made this year should give you confidence that we can get there, particularly as oncology overtakes women's health as the largest part of the business over the next few years. We've also clearly ramped OPEX, but very little of the OPEX increase translates to revenue in the same calendar year. These are not Super Bowl ads meant to drive short-term volume growth. These are primarily investments that are designed to deliver growth in 2026 and beyond, along with the roughly $60 million in accruals that don't repeat every quarter, as Steve described. As a result, we are really pleased to be showing leverage in the business with respect to free cash flow generation, and we are significantly bumping up our expectations for cash flow generation for the full year. The balance sheet remains pristine with no permanent debt on the books and the cash flows from operations pushing our cash balance above $1 billion currently. Okay, let's get to the guide update on the next slide. For the third time this year, we are completely resetting the revenue guide, now ranging from $2.18 billion to $2.26 billion on the strength of the revenues and the volumes we've seen so far this year. The gross margin guide, we are once again bumping up the bottom end of the range 100 basis points to account for the good results we've generated so far this year. To keep modeling simple, we've forecasted Q4 without true-ups in the revenue or the gross margins, as has been our previous practice, although the record cash collections in October position as well for more true ups when we close the books in q4 looking into next year i think a preliminary way to think about volume growth for women's health and organ health is to post a similar number of growth units as we delivered this year given the teams are relatively stable in size and for signatory units we continue to think about the last four quarters rolling average as a good goal for unit growth over the course of the year so of course there may be some variation quarter to quarter. That implies some very healthy quarters for Signatera next year, but we think that's justified given the strength of the team we now have in place and the drumbeat of prospective outcomes data we've continued to deliver. On ASPs, I think a reasonable initial forecast would be to hold Women's Health and Oregon Health ASPs stable with some modest growth built in for Signatera and perhaps the $50 range through the course of the year. Our internal teams are, of course, focused on much better results than that across the board, but even this approach yields some big revenue numbers when paired with the volume scale we are expecting. On both the SG&A and R&D lines, we are making the bumps that Steve described in his section. Steve pointed out that SG&A was flattened down sequentially in Q3 compared to Q2, and R&D was up on all the additional launch efforts and clinical trial work we took on. We'll remain opportunistic on additional OPEX investments, particularly in R&D and clinical trials, but we think the commercial operations are well scaled now to support continued rapid growth in the coming years. Accordingly, I'd expect OPEX growth to grow something more like in the 10% range next year with a bias toward the R&D line. We are in the midst of our budgeting process now, and we'll plan to give another update on 2026 when available early next year. I mentioned cash flow generation as a huge bright spot in our results this year, and we expect to sustainably generate cash again next year as we continue to get scale with top-line growth and improving margins. Okay, with that, let me open it up to questions.
Operator
Thank you. Ladies and gentlemen, we will now begin the question and answer session. At this time, I would like to remind everyone, in order to ask a question, please press star followed by the number one on your telephone CPAS. And if you would like to withdraw your question, simply press star one again. As a reminder, please make sure that your phone is not on mute when asking your question. Our first question comes from the line of Tycho Peterson with Jeffries. Please go ahead.
Hey, this is Noah on for Tycho. I wanted to start by asking on prenatal. So, you guys announced the new fetal focus test last week. I guess why is now the right time? What were you hearing feedback-wise on the five-gene panel? And then with looking at the 20-gene panel, how are you thinking about reimbursement there?
Yeah, thanks. That's a good question. So, you know, of course, we, you know, we launched the five-gene panel earlier this summer, I think August, something in that time frame. You know, that's gone really well. We've gotten great feedback from, you know, from customers. And now, you know, RD has gotten to the point where we're in a position where we can launch the broader panel, which was always part of our plan, so we're excited about that. We're also excited about the EXPAND clinical trial. This is something that we started several years ago. If you go back and, you know, you take a look, this type of trial is really the gold standard where we're prospectively collecting blood tubes and then collecting diagnostic outcomes on both positive and negative samples, effectively on all the pregnant patients that enroll into the study. And that's really the gold standard way to run these types of trials. So we're excited for that to read out over time as well. We think that will really be the defining trial in this phase.
Got it. And then for my follow-up, switching to MRD here, coming out of ESMO and the InVigor readout, how are you thinking about the path to NCC guidelines with some of the clinical utility data you put out and then subsequently the broader commercial payer adoption? Thanks.
Yeah. So, you know, obviously we're really excited about the data from ESMO, you know, particularly around InVigor that's been received very well. Alex, do you want to comment on guidelines for a moment? And maybe, Solomon, if you want to comment as well.
Yeah, thanks, Steve. So, we do want to know that the Invigor011 data is what we call level 1A clinical data and has been obviously submitted for FDA approval, both for the, you know, the compound as well as for Signatera as well. If you look at past precedents, you know, typically if something does go through the FDA process, it is included into the NCCM guidelines. So, while we can't really speculate on how CTA will be described in CCM guidelines, we do expect that, you know, Signatera and ATISO kind of guided by Signatera in the setting will eventually make it into the NCCN guidelines?
Yeah, this is Solomon. I would add, given that the New England Journal paper has already come out, assuming that all the FDA processes are on track, we would expect to see a guideline update at some point mid or late next year.
And just on the final point on this on commercial payers, which I think you also asked on, you know, we're definitely starting to see some traction, as Mike mentioned, from commercial pairs because of the biomarker bills, but obviously generating this level of evidence and just the quantity of data that we're generating, we think puts us in a good spot longer term to have coverage from commercial pairs.
Operator
Our next question comes from the line of Doug Schenkel, which will research. Please go ahead.
Hey, good afternoon, guys, and thank you for taking my question. I'm going to keep it to one topic, early cancer detection. First thing is regarding the proceed CRC advanced adenoma sensitivity specificity performance. I'm just wondering how important that was to shaping your willingness to invest more in this program and kind of related to that. Generally speaking, are you using the same standards you applied in advancing your NIPT and then MRD programs, two areas where you clearly made the right call to move forward so that that's the first part uh second how much would you expect to invest in 2026 i'm guessing you know something like 50 million dollars incremental um in that program and then lastly i'm curious if you'd be willing to share minimum performance uh minimum viable performance you would consider to move forward with this product from a commercial viability standpoint? Thank you. I'll get back and listen.
Yeah, thanks, Doug. Yeah, all good questions. So, I would certainly say the performance that we've achieved, you know, definitely shaped our willingness to invest into the program. You know, coming out of the JPMorgan conference, you know, in the beginning of 25, and then with our initial pilot readout on advanced adenoma. Based on that, we made the decision to initiate the initial stages of the FINE study because we were feeling very positive about the roadmap of improvements that Alex mentioned on advanced adenoma. But we didn't fully pull the trigger until we saw this most recent readout from the PRECEED study, which was, I think, a big milestone that we were waiting for. And now based off this and our own internal views of the performance and all the, I think, things that Alex outlined just a few moments ago, we're really full steam ahead on the FINE study. And we're excited about it. We've set everything up the right way. We've gotten a jump start by running the PRECEDE study and then having, you know, all the ducks that are rowed to start collecting patients. And we think we can enroll the trial in 2026 and hopefully be, you know, one of the major players in, you know, this early cancer detection space, which we think is a really good opportunity. You know, I think from an investment standpoint, you know, I think you're kind of directionally right, you know, just kind of building off what we spent this year, you know, I think that, you know, that kind of makes sense. And, you know, from a minimal viable standpoint, you know, we've always said we think we have to have, you know, really strong performance to make it worthwhile. And, you know, that's what we're seeing right now, very strong performance. We know where competitors are. And, you know, I think that's something we're, of course, keeping in mind. But, you know, again, it's a huge market. You know, we've done well in very competitive environments. So, you know, we're going to keep our eye on just where we need to be and be pushing as hard as we can to make sure we're setting up for success. Thank you very much.
Operator
Our next question comes from the line of Daniel Brennan with TD Cowan. Please go ahead.
Great, thank you. Maybe just on Signatera, you've kind of taken up the guide for giving us some color on next year in terms of kind of an 18,000 plus or minus trend line. Maybe can you just unpack a little bit, you know, a nice little bump up again this quarter above what you guys were expecting. Just any color. I know you gave some drivers in the prepared remarks, but just can you dig in a little bit specifically, anything unique really stand out. And, you know, if you do hit that kind of 18,000 sequential run rate, which would be a step up from the prior guide, it is still a decel from what we've seen the last two So is there anything in the last two quarters that was unusual that would cause the deceleration or is it just, you know, general contributism?
Yeah, good question. I mean, look, I think the growth at this point is really just coming across the board. I mean, we're seeing a lot of new customers coming on, you know, using Signature for the first time. We're seeing existing accounts and doctors, you know, extend their usage. We're seeing new histologies come on. And I think what's, you know, what's really remarkable is just, I think, the very low penetration, you know, that we're in right now. You know, I think despite all of our success, I mean, we're still kind of in these very low single digits when you look at overall penetration, including recurrence monitoring. So there's a long way to go. And, you know, as long as we keep putting out, you know, high-quality data, I think we're going to be in a great position. In the last couple of quarters, we've seen really strong numbers on new patients coming in, which I think has been, I think, significantly more than what we've seen historically. And anytime you see a very sharp uptick, it's something that you always have to kind of think, okay, well, that may normalize over time. You know, but I'll tell you just as we started Q4, I mean, obviously, Mike mentioned this as well, the prepared remarks. I mean, we're seeing that same strong trend on new patients continue. So there seems to be a lot of interest. But just having been, you know, having having, you know, all been in the in the space for a long time, you know, we know it's not always a straight line up. And, you know, I think kind of the way that Mike put the framework in place, you know, is the right framework to think about. But, you know, we hope to exceed that as we have been doing thus far.
That was super helpful. And maybe just kind of saying on senior tariff, if you don't mind, just you talked about the biomarker bills. You know, Mike gave the $50 kind of price increase over the course of the year through the end of 26 is like a decent starting point. And you talked about early progress, and you guys have been signaling that for a little bit. Can you just spend a little more time on it? I mean, I guess our thinking was, you know, when and if biomarker bills begin to have an impact, it could be a bit of a domino effect where it'd be tough for a payer to cover something in Texas and not in the adjacent state. So just any more color on specifically what you're seeing and is that still a potential in 26 or do you think it's going to take longer for biomarker bills to really kick Mike, do you want to take that?
I think that there's going to be, look, I think that you'll have a continued drumbeat from biomarker state reimbursement over the course of 26. I mean, I mentioned in my prepared remarks that we've seen the growth that I'd hope to see in the ASPs from the biomarker states. And that was really based on wins that we had kind of in the spring and in the summer. There is something to the idea that, hey, like when you have like these big national plans and they've got to get it set up to cover Signatera in one area, but then not the other. And the clinical utility and the cost savings is so obviously there. Does that add to the incentive structure for them just to cover the test more broadly? When we end up kind of getting the steady state and we are kind of broadly covered in a pan-cancer setting, which I think is inevitable, I think we'll look back and see this as one of the drivers. But you won't be able to tease that out versus all of the excellent prospective outcomes data that we've been publishing and that we're going to have in the future. But, yeah, I think it's a factor.
Operator
Our next question comes from the line of Subu Nambi with Guggenheim. Please go ahead.
Thank you for taking my question. Solomon, your prepared remarks described the advanced adenoma samples in true seed trial helped us understand why you believe the study is designed in a way to be more predictive as we head into the fine study readout. That said, what I'm still missing or not understanding is why is your assay different and then better able to address what has been an issue for others? Low signal abundance and really just the biological limits in ctDNA. What is so unique about your assay?
Yes, good question. Alex, why don't you take that?
Yeah, thank you for that question. I think it's a multitude of factors and also just the dedication of our research team. You know, this has been a multi-year process, and we've really approached this, I would say, from first principles. First of all, it's finding the best biomarkers, prioritizing advanced adenoma as, you know, something to be really focused on and not necessarily just CRC by itself. I think the technology has also advanced in the last few years that has allowed for increased molecular recovery, lower sample loss, and also techniques that, you know, help differentiate, you know methylated regions that otherwise might have been you know difficult to pick up and then I think lastly it's using the right samples you know I think we've benefited tremendously from having access to one of the largest repository of early stage colon cancer cases with known VAS from Signatera so when we're training and designing our assay you know, we're able to really focus on the cancers that matter and that are traditionally difficult to detect. I think that's what's given us a lot of confidence now over multiple readouts, you know, that we are on the right track. And I think this study in itself, you know, furthermore kind of underscores that. Collected in exactly the same fashion, prospective asymptomatic patients, distribution of the advanced abnormals is representative, if not a little bit tougher than you would expect in a much larger study. And, you know, we're seeing performance, you know, that gives us strong confidence that this is likely to hold up in a larger perspective FDA-enabling study.
Very helpful. Thank you so much for that. Quick unrelated follow-up. When should we expect the Vega trial to read out the de-escalation arm of the Galaxy study?
Alex, why don't you jump on that one, too?
Yeah. Yeah. So, it's difficult for us to predict exactly when the study is going to read out. It is an event-based readout. I will say that all patients on the Vega study have been randomized. So, we're just waiting for enough events. I think it is safe to say that the readout is likely to occur in 2027. But as we get closer to that, you know, we'll refine that guidance.
Perfect. Thank you so much. Thanks.
Operator
Your next question comes from the line of Casey Woodring from JP Morgan. Please go ahead.
Great. Thank you for taking my questions. I have a couple of quick ones on Signatera. Was hoping that you guys could split out contribution from new patient starts in the quarter and whether that increased from last quarter. I know you called out strength there last quarter as well. And then today you've noted an acceleration across multiple tumor types in Signatera. Just curious if you can clarify, you know, which tumor types you're seeing the most strength and if you're seeing any early traction from new data readouts like InVigor?
Yeah, it's a great question. So, yeah, I mean, we had, I think in Q2, we had sort of said that the growth in new patients was an all-time record, and I think it was something like maybe 2x greater than anything we'd ever seen before. And what's incredible is in Q3, we basically saw something similar where we kind of had you know, almost to those same levels of new patients coming in, new patients starts coming in. Of course, it was, you know, I mean, we had more new patients coming in, but the growth quarter over quarter, you know, was almost to this, you know, record level of growth that we had seen previously. Sorry, I just had to clarify. But, yeah, so, you know, I do think we're seeing a lot of continued interest with new patients coming in. With regards to where we're seeing interest, it's really broad across the board. Wherever we generate a lot of data, there's a lot of interest. And of course, coming out of the Invigor announcement, there's been just a ton of interest in bladder. We're getting a lot of inbounds, both interest from farmer companies as well as physicians that are now looking at how they can implement this in either trials or in their practice.
Got it. That's helpful. And then just my quick follow-up here. Appreciate the top line and OPEX color on 26, but can you just talk about gross margins? How should we think about those, especially as Signatera becomes a larger part of the mix? Would you expect those to step up at a similar rate as they did here in 25?
Would that be a good benchmark um thank you yeah uh mike you want to take that yeah i i think on the gross margins i think um first um as i've mentioned the preparator marks i think it's it's just it's easier to model if you strip out the trips and so you start with kind of the pre-trip number and anchor to that and then i think that we can have a reasonably meaningful um kind of sequential improvement uh over the course of next year in gross margin as we continue to grind higher Obviously, it's hard to repeat the same exact rate that we had this year. I think, you know, we're up, you know, some, you know, four percentage points or something like that year on year. It's a pretty meaningful change. But I do think that, you know, the target remains clear to us. I mean, I think we can be in that 70% range over time. And I think even inclusive of the true of, I think that 64.9% number that we put up this quarter, that gives you a glimpse of what we're capable of. So I'm feeling very encouraged on gross margins. I do expect improvement next year.
Got it. Thanks for taking my questions, guys.
Operator
Our next question comes from the line of Kunitsuda with the RISP Partners. Please go ahead.
Hi, guys. Thanks for the questions, and congrats on a strong print here. First question is more on the signatory side. Just trying to understand what the ASP increase, is that the assumptions for next year? is that just on biomarker bills, or are you baking in additional indications that you talked about? So, maybe could you clarify on that point? And then on the clinical side, it would be great if Alex could provide more on, you know, when we look at the PEGASIS and Dynamic 3 trials out there, given what we've seen with some of the struggle around de-escalation, how are you thinking about Wega there. And then I have a follow-up. Thank you.
Mike, you want to take the ASP call?
Yeah. So on the ASPs, I mean, honestly, on secondarily, if we do the things that we think internally we can do on both biomarker states and given all the moldex submissions that we have in flight, I think we can do better than the $50 I mentioned in the prepared remarks. One thing to note is that we will have another kind of reset on ADLT, which would be a modest headwind for us going into next year so i just want you to be factoring that in uh so the 50 represents what i hope will end up being kind of a conservative cast of um of achieving you know some fraction of all these opportunities we have ahead of us he kind of talked about this but we've all been in this space and been together for a long time and unfortunately it doesn't always go up into the right you don't always get 100 of these opportunities to flow in at the time that that you want them but you know if you break down multi-ex emissions we have a launch track record of being successful with those and then driving asp improvements off of those i think the biomarker state uh is a is a driver that you know we started to really show some traction there uh as well um and then you know there's some other opportunities related to um you know potential guideline inclusion uh with bladder and beyond uh that could be very exciting as outside but i think just as an initial kind of preliminary kind of glimpse in the 26th, I think that's the right starting point.
Great. And, Paneet, thanks for the question regarding Vega. It's hard for us to comment on, you know, other readouts, but I will say that, you know, obviously assay performance is important, study design is important. You know, I think when Vega was designed, a lot of thought went into the right approach. I will find that in Vega, you know, there was serial testing patients could cross over and get delayed treatment as part of the Altair study. So that's one factor to consider. I think the other thing I want to point out is we do benefit a little bit from the fact that Galaxy actually was the basis for enrolling patients into Vega, and we have been able to see now over a period of multiple years how the assay has performed in the non-randomized Galaxy patients, which does increase our confidence. um and you know i think you know lastly you know it is a larger study um you know close to a thousand if not more patients were randomized and you know it's hard for me to obviously predict exactly the outcome but you know we remain confident and excited to see the data uh when some blind in 2027. okay um that's helpful and then just a follow-up on the women's health side
We've seen growth from a competitor in the market, a mother-only assay that has gained traction. So obviously, you have a fetal-focused product now. Could you talk about the positioning of the product, if the sales force is fully trained on it? How can you go into market and capture share? You obviously have a strong commercial position here. So maybe talk about how should we think about that piece of the market and your positioning and growth there.
Yeah, that's a good question. So, yeah, I mean, we've been doing carrier screening for a long time, right? I think we're maybe, you know, one of the largest providers of the next-gen sequencing-based carrier screening in the U.S., and, you know, when you screen the mother, if the mother's positive, then the standard of care is to go screen the father. Now, one of the challenges is that the father is not always available to get tested or maybe not willing to get tested. And so there's, in those cases, there's a clinical need to be able to directly assess the genetic status of the fetus. And what's great with fetal focus now is that we can do that. We launched the 5G panel in, I think, August. That was received very well. Now we're sort of expanding to the 20G offering. And, of course, this is something we can roll out through our entire customer base. We can roll this out broadly through our existing sales team. And then there's a lot of, I think, competitors that maybe don't have this capability where, you know, this gives us, you know, another advantage where we have something unique, you know, compared to them. And then, you know, for the groups that do have it, we think we're positioned very well, both with our technology and with the clinical trials that we've been doing. So, as I said, you know, there's kind of always been competitors in the space and we've done really well. You know, we're very pleased with our growth in the women's health space i mean we we can kind of see sort of where others are growing and how we're growing and and we think we're doing you know we're doing very well there um and you know we we think this can can actually um increase that as we move forward got it all right thanks guys conference again next question comes from the line of katherine schulte with bayard please go ahead hey guys i'll just go ahead and ask both my questions now um first on early detection we've seen some players start in one cancer and then move on to multi-cancer applications.
And you've expressed interest there as well. Obviously, you want to figure out CRC first, but any updates on your long-term strategy and screening and, you know, maybe when we could hear updates on the multi-cancer side?
And then second on Cignatera 2026 volume growth, just to confirm, was your comment to look at the rolling average of the last four quarters in terms of sequential unit volume growth so 18 000 or so and does that level hold up for the fourth quarter as well thanks yeah thanks so i'll just comment on the first one i mean i think the you know our focus you know right now has been you know getting this the crc product um you know completed through the the clinical trial process and approved no market you know but of course in the background we've got a lot of activity going on, and we have an excellent team. And so MSET is something that, of course, we think we would be in a good position to do and to perform well on. So just kind of stay tuned there. But in the near term, we think there's a big opportunity in CRC, and we think we're going to be one of the major players in this space. And it's an attractive opportunity when you look at ASPs, gross margins, and just the clinical need and the total market size. Mike, do you want to take the second question on, you know, just kind of what we're thinking from a forecast standpoint on Signaterra?
Yeah, Catherine, the way you said that, I think, is right. I mean, what I had in mind there is kind of the rolling four, for the growth, rolling four quarters, average for the growth units. And, you know, I just stress that's not, you know, every quarter is not, it cannot always be up under the right. You don't always exceed that rolling for every quarter, even though we have, you know, up to this point. But I think it's, you know, you got to have some kind of benchmark, I think, for modeling. And I think that's a very healthy one that requires very good execution from our team. And I think if you're able to look at it over the year, like looking back on it, I think we'll be able to hit that bar.
Operator
Okay, ladies and gentlemen, that is all the time we have for questions. This concludes the question and answer session in today's conference call. We would like to thank you for your participation.
