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44th Annual J.P. Morgan Healthcare Conference

Jan 14, 2026

Casey Woodring
VP of Equity Research, JPMorgan

Healthcare conference. My name is Casey Woodring from the Life Science Tools and Diagnostics team. Pleased to be joined by the management team of Natera. The company will go through their corporate presentation, then we'll do the Q&A session afterwards, so with that, I'll pass it to Steve.

Steve Chapman
CEO, Natera

Yeah, great. Thanks for having us. This is the standard Safe Harbor. So the mission of Natera is transforming the management of disease worldwide, and we do that with a proprietary technology that can detect extremely tiny quantities of DNA that combines molecular techniques with bioinformatic techniques that were developed at Natera. We first applied this technology in cell-free DNA in 2013 with Panorama, which is a cell-free fetal DNA test that looks at chromosomal abnormalities. We were the fourth company to launch in a very competitive market, but today we are by far the market leader with more than 50% market share. We took that same technology and we applied that in the field of organ health, where we look at donor-derived cell-free DNA in the setting of an organ transplant to identify rejection non-invasively. Our product there is called Prospera.

And then, of course, in the field of oncology, where we look at circulating tumor DNA in the setting of minimal residual disease or recurrence monitoring, and our product there is Signatera. So we've been quite successful over the years, and we follow the same formula for success. Number one, we want to always have leading-edge technology and focus on constant innovation. The second is to be the leader in peer-reviewed, published clinical data. The third is to have excellent customer patient experience. And then the fourth is to have broad and talented commercial teams. So 2025 was a great year for us from a volume standpoint. We had a record year in women's health, in organ health, and in oncology. We just released our Q4 numbers, and you can see we had 924,000 units in Q4, driven by incredibly strong growth, particularly in Signatera MRD.

In Signatera, we were pleased to announce the fastest growth quarter ever in the history of the company. We had 22,800 growth units over the previous quarter for a total of 225,000 clinical MRD tests in the quarter. We were super excited about the acceleration that we saw really pan-cancer across multiple different tumor types. This is driven by very strong data readouts that we had in the second half of the year and just a continuation of the strategy that we've had throughout the course of the year. Revenues were up 39% in Q4 over 2024 and similar period, with $660 million that was driven by very strong ASPs across the board and outperformance on volume, as I showed on the previous slide. We also had record gross margins and very strong cash generation for the year.

In fact, we actually had greater than $100 million in free cash flow generated throughout the course of 2025, so now I'm going to shift gears a little bit and talk about some of the innovation that is driving the growth or that may drive growth in the future, so first, in women's health, we recently announced the 21-gene single-gene NIPT test, which we call Fetal Focus. Now, historically, with carrier screening for autosomal recessive diseases, you screen the mother, and if the mother's positive, you screen the father. And if the father's positive, then you get an amnio or CVS on the baby to find out their risk of severe genetic diseases. Well, the challenge with that is sometimes the father's not available and you're not able to complete the screening module.

So we developed a new test, a single-gene NIPT test called Fetal Focus, that enables us to look at the cell-free fetal DNA directly to look at these severe autosomal recessive and X-linked disorders, things like cystic fibrosis. We think this is filling a major gap in clinical care, and we're seeing a lot of excitement around this product. So the product leverages our ultra-sensitive linked SNP technology. We're doing a broad assessment of over 21 genes. We think this is today the largest panel that's available throughout the industry. We offer the test as a frontline offering, those that just want to order it upfront, or as a reflex test where you can screen the mother and then attempt to get the father. If the father's not available, you can order the reflex test.

This is all based on a very robust clinical trial that we did called the EXPAND study. It's still ongoing, where we're collecting about 2,000 samples. Uniquely, we have genetic outcomes on all the positives and all the negatives in the study. We recently reported a readout from the EXPAND trial where we had 96% sensitivity with 98% specificity across approximately 300 samples. Again, we have about 1,800 enrolled to date. We're enrolling 2,000 samples overall, roughly. Really excited about this product. There's a very significant amount of interest in this category by physicians, and we've seen a lot of new close customers in kind of the tail end of Q4 and leading in now into Q1 as a result of having this in the portfolio. In oncology, we've also been innovating.

So last year, we talked about launching tumor-naive MRD, and we also talked about launching a genome backbone for our Signatera tumor-informed MRD test, and we did both of those, so we launched a Latitude tumor-naive MRD product in colorectal. Results have just been accepted in a major publication, which should be out in the next couple of months, and then we'll be submitting for reimbursement there. We're also now expanding that to other tumor types as well, and with our genome test, we had a successful launch. We can get down to one part per million LOD, so extremely ultra-sensitive, and that had a great reception in the field. We've seen uptick there exactly as we thought we would, but we're not done innovating, and we were excited with the recently announced acquisition of Foresight Diagnostics because this adds to the ultra-sensitive strategy that we have in MRD.

Foresight has a unique technology that they call phased variants, where there's two variants that are traveling on the same homolog. And this allows you to get really exquisite levels of sensitivity and limit of detection down to one part per 10 million. So I just announced previously, with the standard genome testing and traditionally ultra-sensitive tests, they're talking about one part per million, maybe three parts per million. Here we're talking about one part per 10 million and an LOD 95 that's been shown to be three parts per 10 million. So we're now in the process of incorporating this proprietary phased variant technology into the Signatera test. And in short order, probably in late spring, early summer, we're going to be launching a new version of Signatera that incorporates phased variants and structural variants and increases the number of variants that we're tracking.

Now, we're still going to be taking our same tried-and-true multiplex PCR NGS method that does extremely deep sequencing, like roughly about 150,000x coverage at each of the variants that we detect because we think that that's the best approach rather than doing thousands of different variants. But by incorporating phased and structural variants, plus slightly increasing the number that we're tracking, we think we really have now a gold-plated MRD test that is really incredible. And I'm excited to be in a position to roll that out. In addition, we also are able to now move into the lymphoma and hematologic cancer space with Foresight, and that's an exciting area where they've generated incredible data. They have phase III clinical trials going, and we're excited to be partnered with them to move into that space.

So in addition, we think the next wave of innovation beyond ultra-sensitivity will come from enhanced MRD. And we're excited this morning to announce an enhancement that we've been able to develop, which is based on AI and a foundation model that we built that looks at digital pathology, that looks at the entire genome and exome sequence and transcriptome where available, combines that with over a million longitudinal ctDNA time points and clinical records longitudinally collected on all of these about 300 patients. We've taken all that together and we built a foundation model where now when we get a ctDNA sample, we can take the digital image, the MRD result, plug it into the model, and get an augmented MRD score that actually can improve the overall precision of the risk score that's given.

Now, we've generated statistically significant data that shows that this augmented model using AI and using our foundation model can improve upon ctDNA alone. And we're in the process of submitting that to ASCO. So we think in the future, when you order an MRD, we'll get all of this other information, digital pathology, we'll get your genome sequence from the tissue and from your germline. We plug that into our model and we can give you not just the ctDNA score back, but also this unique AI-driven score that comes out of our foundation model. So we should be rolling that out roughly mid-year. And this is really unique to Natera because to generate this type of model, you saw the partnership we announced with NVIDIA.

To generate this type of data, you have to have, or this type of power with the foundation model, you have to have millions of data points to input, and we have more early stage and adjuvant stage tumor genome and exome sequencing and more longitudinal ctDNA time points and clinical data than any other company has ever generated, so we're uniquely able to do this to improve upon and augment traditional MRD testing. Now, we're also working on AI enablement in other areas, so one is to just use these foundation models to identify new prognostic and predictive signatures or in partnership with pharma companies to develop new actionable drug targets that they can go after. Another area that pharma is interested in is real-time patient matching. As I said, we have all this early stage data that nobody else has.

It's a very different set than what other companies have. And since we announced our AI initiatives, we've seen really a significant number of pharma companies that are interested in partnering with us and getting access to our unique data set and our unique capabilities. Another area where we've built a moat and we're continuing to invest is in clinical data. So obviously, we had a very significant amount of clinical trials readout in 2025. Most notably, I think, was the IMvigor011 trial that was featured in the New England Journal of Medicine, focusing on muscle-invasive bladder cancer. But we had many other readouts as well: PALLAS, DARE, I-SPY, all in breast cancer, an area that we previously said we've invested over $100 million in evidence generation in breast cancer. We had the 702 study in colorectal cancer and a series of other trials.

We just had so many readouts that we can't list them all here. But we're not done. We're continuing to invest heavily into data generation and into new prospective clinical trials, both with consortium groups and pharma partners, but also directly ourselves. We've recently announced big trials in breast cancer, MIRADOR, HEROES, and the TEODOR study. And in fact, we have another major de-escalation trial in breast cancer that is to be announced. So we're upping our focus on breast cancer. We're investing another $100 million into clinical trial evidence development, specifically in breast cancer, because we think that there's an important clinical unmet need there. So very significant investment. And then, of course, we just announced the STELLAR study in partnership with Exelixis in colorectal cancer. Now, we think this is a very exciting trial.

It's a phase III pivotal trial that's going to start in mid-2026, looking at their drug zanzalintinib and resected stage two and three colorectal cancer in patients that have completed their initial course of adjuvant chemotherapy but are still MRD positive. So we think this is a great opportunity to take a set of patients that are highly likely to recur and have an actionable therapeutic for them should the trial work out. But what's exciting about this as well, beyond just this particular study, is that all the patients that are getting enrolled are clinical commercial Signatera patients. So because I think now pharma companies are realizing and they're saying MRD positive patients is a great cohort for us to go after and to try to build new drugs to target and to do new clinical trials, we have all the MRD positive patients at Natera.

We know where they are. We generate them as part of our clinical testing business. So pharma companies are now coming to us saying, "Okay, we want to partner with you based on your clinical testing that you're doing to go after these MRD positive patients and build clinical trials on top of that." So this is really just the beginning of this trend to come to Natera and do trials off of the commercial business. And we think this is a great opportunity. This treatment on molecular recurrence concept of patients that are either still MRD positive or are in remission and then become MRD positive is a very significant trend and area that we're seeing a lot of interest. And then last, I'll just touch on our early cancer detection screening initiative.

We are excited to generate very strong colorectal cancer screening data in 2025, and then also solid data in advanced adenoma from the prospective PRECEDE trial that we announced at the end of 2025. In 2026, our goal is to complete enrollment in the FDA-enabling FIND study. We are well underway now enrolling. In fact, our run rate for enrollment right now is already 20,000 patients, and that's before we turn on a bunch of new sites and a bunch of new recruitment channels. We're super excited about the trajectory that we're on, actually ahead of schedule. We think we're going to be able to collect 35,000+ patients this year, complete the enrollment, and be in a position to submit to the FDA in mid-2027, which is our goal.

We think this is a big driver of growth for Natera in the future, and we're excited about this opportunity. So last, I want to finish with a series of milestones for 2026. First, we have mentioned we have submitted for expanded MolDX coverage. About 30% of the tests that we run today are in a category where they're not necessarily covered under Medicare. We said in December we had submitted seven additional MolDX submissions, and we think there's an opportunity to expand upon that as well. So that could be a big driver for us this year. We're also working intensely to integrate the Foresight business. As I mentioned, we're going to be launching Signatera Genome with phased variants and structural variants in mid-2026. We're well underway working with Japan. We think we're going to have regulatory approval this year and be in a position to launch.

We're expanding our tumor-naive Latitude test into other tumor types. In women's health, we've launched the Fetal Focus test now with 21 genes. So we're seeing extreme interest there. We think that's going to be a great opportunity. We plan on completing the enrollment for the FIND study in early cancer detection. And then in AI and partnerships, we announced our partnership with NVIDIA, which we think is great. We also are in a significant partnership with Ultima Genomics for launching new CLIA products and using their sequencing platforms. And we expect continued growth in ASPs and volume as one of the main drivers. So with that, I think we'll conclude the presentation and open it up for Q&A.

Casey Woodring
VP of Equity Research, JPMorgan

All right, great. Thank you. Thanks for that, Steve. So maybe we'll start. You guys pre-announced the solid top-line beat. Maybe walk us through the performance in the quarter across each segment relative to your initial expectations. And then digging into it, Signatera had another record quarter of sequential growth units. Maybe walk us through the drivers there. And is it fair to flow the strong performance into the 2026 outlook and assume quarterly growth units for Signatera are at the high end or slightly above that kind of 18,000-ish quarter-on-quarter average that you've seen in the last four quarters?

Steve Chapman
CEO, Natera

Yeah, so we really saw 2025 as a whole was a record across all of the different areas that we do business. Women's health, we saw significant growth. Organ health, we saw significant growth. And then, of course, in oncology, we saw significant growth. So I think there was a time not too long ago where if we had grown 15,000 units quarter over quarter, everyone would have been going crazy. But I think now we've reset the bar for ourselves with a record Q3 where I think we grew like 21,000 units or something in that range. And now, again, in Q4, a new record in Signatera quarter-on-quarter growth. We're seeing significant interest. I think the beginning part of December, ahead of the holiday, we saw just very strong weeks coming in, both new patients and recurring patients.

I think the start of the year here, we're off to a great start as well. I've just kind of been watching the numbers come in. So everything is setting up for an incredible growth trend as we go forward. We invested a lot in 2025 in adding salespeople, increasing histology-specific medical directors and teams. And I think as we look into 2026, we're going to start to see some of that investment directly impact the unit growth. So we've got a lot going on. We also had some great data readouts, getting good feedback coming out of ASCO GI as well, which is always good. I think it's going to be another good year.

Casey Woodring
VP of Equity Research, JPMorgan

And you called out share gains in women's health as well as strong growth and significant interest in Fetal Focus. So maybe just walk us through the competitive dynamics in the quarter and how Fetal Focus contributed to growth from a volume perspective in 4Q?

Steve Chapman
CEO, Natera

Yeah, so I think in women's health, we have been in a great position where we've had more than 50% market share. We've been innovating. But one of the areas where I think there's an opportunity for us is in this field of single-gene NIPT. Now, for a period of time, there's been maybe one company that was the only company that had a single-gene NIPT test. And I think that helped them grow and take share. We still grew our share and had a great year. But of course, other companies that had this single-gene NIPT product also did well. But now we're in a position where we have single-gene NIPT. And that helps us both to defend from share losses from competitors that come in and try to take our business, but also to go grow business from competitors that don't have a single-gene NIPT offering.

We're excited about our product. It's the largest panel that's available. We've done a thorough validation. The EXPAND trial, I think, is a very good clinical trial. We've got this unique Linked SNP technology. We're seeing record growth on a weekly basis coming in, significant interest in the product line. I think it's going to be an opportunity for us to continue to grow and continue to take share.

Casey Woodring
VP of Equity Research, JPMorgan

You gave a lot of color on Foresight, but just walk us through Natera's strategy in the lymphoma market, including which specific indications you're interested in targeting, how that Foresight technology will enable this, and what call points that Natera has in this part of the market already, and then the competitive landscape there, and then lastly, beyond lymphoma, what is Natera's interest in the broader heme MRD market, such as multiple myeloma?

Steve Chapman
CEO, Natera

Yeah, so there were really two reasons why we were interested in partnering with Foresight. And the first was the phased variants technology and the intellectual property around phased variants technology. We did a ton of research, and we ran a lot of different experiments. We looked at 5,000 variant panels. We looked at all these different opportunities. And we determined that phased variants is the path to get the most sensitive assay in MRD. And after that, we began our discussions with Foresight, and we were able to acquire the company and get access to the full set of intellectual property plus the proprietary technology. And now we're in the process of incorporating that into Signatera along with structural variants. And that's going to be rolled out pan-cancer across every tumor type. Now, another reason why we pursued the company was for the lymphoma clinical opportunity and pharma opportunity.

Foresight has developed a significant leadership position in DLBCL, non-Hodgkin lymphoma, follicular lymphoma, and we thought that that was an area where Natera, although we've had a small presence, could be helped significantly by the acquisition. Now, that's not a small market. There's something like 70,000 new patients per year, which is maybe just slightly smaller than what we see with stage two and three colorectal cancer, and to be able to just jump ahead and leapfrog several years by acquiring Foresight and partnering with them, we thought was a great opportunity. Now, there's an opportunity to expand upon the list of indications that I just listed off, but so far, I think we're really excited about the DLBCL in non-Hodgkin lymphoma opportunity and the work that they've done, and we're going to secure that and then go from there.

Casey Woodring
VP of Equity Research, JPMorgan

That's helpful. Maybe one on Signatera genome. You had some new data presented at San Antonio Breast from the International Randomized phase III PALLAS study. Looked like that PALLAS looked at the use of MRD in post-surgical stage two and three HR positive and HER2 breast cancer. Walk us through the main takeaways and early feedback from physicians there. How do you see this readout potentially translating to impact on volumes?

Steve Chapman
CEO, Natera

Yeah, it's good. Do you want to take that, Alex? Actually, it could be a good one for you or Solomon.

Alexey Aleshin
General Manager of Oncology, Natera

Yeah, absolutely. Yeah, so I think that was a very large, probably one of the largest adjuvant studies ever run, looking at if palbociclib or Ibrance would improve outcomes in early-stage breast cancer patients. Unfortunately, the study was negative in all comers. So very similar story with the IMvigor010 study that we analyzed a few years ago. And this is the first of, I think, probably two or three presentations I will have on this data that looked at just the prognostic question. Can Signatera at the post-treatment, post-surgical, post-treatment time point on treatment and then an end-of-treatment time point predict which patients are at very, very high risk of recurrence? There's always been a question about any MRD technology in this type of low-shedding breast cancer. Is it sensitive enough, especially from a single time point, to identify?

And we usually say at least around 50%, if not higher, of all the recurrences. And I think for the first time, we have shown definitively that the answer is yes. So I think that really helps kind of move the field forward. And we're also looking forward now to the predictive data analysis, where we're going to actually ask the next logical question. Well, in CTA-positive patients, do these individuals actually derive benefit from palbociclib while the CTA-negative patients do not? And if that turns out also to be a positive finding, I think that's going to be another kind of big advancement in the field, where we basically replicate the whole IMvigor010 story, but now in this much bigger market of HR-positive breast cancer.

Casey Woodring
VP of Equity Research, JPMorgan

In terms of reimbursement, what's the process to get coverage with this new Foresight technology integrated into the Signatera Genome? Do you need to generate new data to submit to MolDX for coverage?

Steve Chapman
CEO, Natera

Yeah, so I think anytime you kind of work on a new assay, it's always important to be interactive with MolDX and kind of make sure that there's a coordination there. And we do that. And I think the relationship there has been positive when we have the data. The key is generating the data. And we're in a position to be able to generate data, send it to them, because we have so many studies that we've done, so many biobanks that we've done. And that's kind of the plan here.

Casey Woodring
VP of Equity Research, JPMorgan

Okay. Maybe moving to the STELLAR trial for treatment on molecular recurrence with Exelixis that you highlighted during the presentation. Maybe just talk a little bit about how the drug's being used in this trial and the potential pathway to read this out and submit to NCCN. Could this trial read out ahead of the other escalation trials like Modern and Circulate U.S.? And could it be the next potential guideline submission?

Steve Chapman
CEO, Natera

Yeah, it's a good question. Solomon, you want to take that or?

Solomon Moshkevich
President of Clinical Diagnostics, Natera

Yeah. I think, first of all, the trial is sponsored by Exelixis. So Natera is partnering on the trial, but it's not ours. We're not running it. I think what's important and exciting about this announcement is it signals where the field is going when Signatera becomes standard of care in clinical practice. So Exelixis, rather than setting up a whole expensive screening arm to test 20 patients to find one positive to randomize into their trial, they're able to come to us, as Steve said, and pre-identify patients who already meet inclusion and exclusion criteria just based on their commercial MRD testing. And that's a big deal because it accelerates the operation of the trial, and it increases the probability of success for trial enrollment.

On the flip side of that, this addresses a significant need for physicians and patients who have completed definitive chemotherapy in stage two and three colorectal cancer. They're positive on Signatera. They do a scan to look for some evidence of disease on a CT scan or a PET or an MRI. Hopefully, they found it and they can intervene. But if not, the doctor and the patient are saying, "Okay, what do we do next?" Now they can go on to this STELLAR-316 trial, which is awesome for the patient. So since Signatera is the only MRD assay that is allowed as part of the enrollment for the trial, we think that also makes physicians more comfortable to come in off the sidelines if they haven't been using Signatera in this way and to adopt it clinically.

There's a really strong network effect here, and we expect more trials like this in the future.

Casey Woodring
VP of Equity Research, JPMorgan

Investors appreciate the size of the MRD market and how early it is in terms of penetration, with Natera currently running the vast majority of tests as of now. Maybe just walk us through how you see Natera's market share evolving over time. In therapy selection, for example, there isn't just one player with 90% share, but maybe MRD is different. So where should or shouldn't we draw parallels to therapy selection, maybe as a proxy for the evolution of market share in MRD?

Steve Chapman
CEO, Natera

Yeah, I think that's a good question. I mean, we're focusing now on penetrating the market as deeply as possible and then making our tests and our offering unique, and I think that's the right approach, and you do that by constantly innovating, so you saw two years ago, we had Exome 16. Now we have Exome 16. We have genome. We just announced phased and structural variants. We launched tumor-naive MRD. We're expanding tumor-naive MRD, so we're innovating. We're spending a lot on R&D. You also do that by generating a lot of peer-reviewed evidence, where we now have, I think, over 100 and something peer-reviewed publications and interventional trials, FDA-enabling trials, and that really sets you apart.

And so there's other areas where you can look, like for example, with RNA expression profiling, where there's been one player that got 95% market share, and they've been able to maintain 95% market share by doing the big clinical trials, by generating the data, and by having their first mover advantage. And I think we're hoping to follow that path, and we're trying to do all the right things and make all the right investments to maintain significant share down the road. And so far, I mean, we launched in 2019. Here we are, seven years later. And I think we're still in an excellent position.

Casey Woodring
VP of Equity Research, JPMorgan

That's helpful. Maybe shifting to early cancer detection, Natera has made meaningful strides here in 2025, including releasing multiple data sets and initiating enrollment for the FDA-enabling FIND-CRC trial. With so much going right for Signatera and MRD, maybe walk us through why early cancer detection is worth pursuing, including running a large outcomes trial, which requires meaningful investment.

Steve Chapman
CEO, Natera

Yeah, that's a good question. So MRD is extremely underpenetrated right now. We think it's low single-digit penetration, and we're investing heavily there. But we've also built capabilities to develop technology that we think can solve some of the biggest problems, like for example, early cancer detection. And our technology is working incredibly well in our initial studies and in the PRECEDE prospective trial, and so us to be able to run the FIND study and bring this to market, I think, is well within the scope of what Natera is capable of doing. And we think it can have a big impact on patients. We think it's a huge TAM. Some say maybe $50 billion or $30 billion. So it's definitely worth pursuing, both for the impact we can have on patients, but also for the overall financial impact on the company.

The FIND trial is already well within our budget. It's already built into our budget for 2026. We generated $100 million in cash last year. On our balance sheet, we're in a great position. We think it's worth us pursuing.

Casey Woodring
VP of Equity Research, JPMorgan

Maybe as a follow-up, Natera released encouraging data on advanced adenoma sensitivity for your test, as shown in the PRECEDE CRC trial. Historically, we've seen some degradation in test performance when moving from case-controlled smaller-scale studies to full FDA trials. Maybe walk us through your view on why this degradation, particularly in AA sensitivity, has occurred historically, and what is Natera doing to mitigate this in the FIND-CRC study?

Steve Chapman
CEO, Natera

Alex, why don't you take that?

Alexey Aleshin
General Manager of Oncology, Natera

Yeah, absolutely. So I think this is something we've been kind of paying attention to now for a few years. And again, I can't speculate for other studies, but I think there has been concern that certain case control studies selected advanced adenomas from a different set than normal controls. The advanced adenomas might have been symptomatic. And all of that can create some bias, where it's a little bit easier to detect those lesions. I think when we set out to kind of really develop and validate our assay, first of all, we said, "Hey, we have some time. What can we do to really optimize the technology upfront?" So we did extensive discovery. I think we also had the ability to test samples that had gold-standard Signatera results. So if you're detecting a signal, you can verify it's correct because you do have that matched Signatera.

Then also, I think we were able to optimize the technology. When we went to actually start clinically validate the assay's performance, we said, "Well, let's make sure we use samples that as closely represent the FDA-enabling study as possible." PRECEDE is really actually the same exact study. It's the same centers. It's using the same enrollment criteria, using the same vendors for sample storage and processing. I think because of that, we are really confident that we are really testing an average-risk population that is as representative of the FIND study as possible. I think that's when we see those results, I think that we are encouraged that at least we're taking all the right steps to minimize the risk of degradation. Obviously, we can't predict the future, but at least that's been our kind of strategy from the very beginning.

Casey Woodring
VP of Equity Research, JPMorgan

Helpful. Maybe just one on the model. Maybe we can loop in Mike here. 2025 was a significant investment year for Natera, with commercial team expansion, new product launches, meaningful data generation. You pointed to a preliminary framework of 10% year-on-year OpEx growth in 2026, weighted towards R&D. Maybe walk us through the long-term framework for operating margins and how investors should think about operating leverage in the business.

Mike Brophy
CFO, Natera

Yeah, no, thanks for the question. I mean, I think the general framework is that we're just going to grow into profitability as the top line matures. So in order to grow that top line, you've got to have the infrastructure in place just a little bit ahead of time. That's exactly the process that we undertook to go from being a cash-burning enterprise to now one that consistently generates cash. So I'll just remind you, going back to 2022, we got to a point where we were burning about $100 million per quarter, and we set out a target to get to cash flow break-even within a couple of years, and we hit that target exactly. If you look at our operating expenses back then as compared to now, in absolute dollars, the OpEx is much bigger now than it was when we were burning cash.

The difference is that the top line, the revenue line, is just more mature. We're further along in the commercialization and reimbursement for Signatera, and we still have miles to go on that front, while the OpEx line, in terms of the operations, are getting much more mature. We've got a fully mature revenue-cycle operation team now that can actually get leaner going into the future. Same to be said for kind of more broadly on Signatera operations and just clinical commercial kind of operations in general. On the commercial front, just in terms of our sales reps' counts, we had to make a very meaningful investment in just getting our sales, our commercial operation, to scale with other players over the last year, where previously we've been subscale, and from here, there's not really an obvious need to kind of double that team again, right?

Meanwhile, the revenues absolutely can do that kind of doubling. So I think we'll just kind of naturally kind of grow into first EBITDA profitability and then EPS profitability.

Casey Woodring
VP of Equity Research, JPMorgan

Okay. Maybe we have one more minute here. Just on the Signatera ASP front, you pointed to Signatera ASP stepping up $50.26 to maybe exit the year somewhere in the $1,250 range. There are a few moving pieces to that. You have a headwind from the ADLT rate resetting, offset by biomarker bills, and closing the gap for Medicare Advantage and covered tumor types. So can you just walk through the puts and takes and the drivers to get to that net $50 increase?

Mike Brophy
CFO, Natera

Yeah, I mean, Signatera ASPs were, again, positive in Q4. And I'll just note, just on the presentation, all the results for Q4 were preliminary, and we'll have final numbers when we file the 10-K. But I expect ASPs to be positive in Q4, growth in Q4 over Q3. I expect to have growth in Signatera ASPs in 2026 over 2025. You mentioned some of the puts and takes. You have some ADLT modest headwind, but you've got a lot of positive drivers as well. I mean, Steve made reference to the huge amount of effort we've put into getting Medicare reimbursement for a much broader swath of tumor types. That's kind of number one on my list. You've got the biomarker state laws, which will continue to be a tailwind.

Then the other piece I'd say is we still have just kind of generalized execution where we can just actually get reimbursed for covered tests kind of across the portfolio. I think Q4 is indicative of what we can see through 2026, and I expect that to be modest improvement in ASPs from here.

Casey Woodring
VP of Equity Research, JPMorgan

All right, well, it looks like we're at time. We'll have to leave it at that. Thank you to the Natera management team for joining us. Thank you for everybody for joining us here. Enjoy the rest of the conference.

Steve Chapman
CEO, Natera

Great. Thank you.

Alexey Aleshin
General Manager of Oncology, Natera

Thank you.

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