Hello, good morning, everybody. My name is Jim Fehrenbach. I'm the COO of the equities business at Piper Sandler, and I'd like to welcome you all to the second day of our 37th annual healthcare conference. Yesterday, we had record attendance, all-time record attendance, even with the rain. That was a bit of an ugly day. I personally like to thank all of you for attending. We genuinely appreciate it. We don't take it for granted. We couldn't do it without you. We have a beautiful day today, and to kick things off, we are going to have Michael Brophy, who's the CFO of Natera, and Dave Westenberg, who is a senior analyst and managing director for Piper Sandler. Gentlemen, take it away.
All right, thank you very much. So, Mike, I'm going to start you off with the strong Q3 and the whole business. But you already have over $500 million in revenue in MRD, and it's growing in the double digits. So, as we said, about the next two to three years, it's likely to be over $1 billion in revenue in that time. So, just how do we think about the law of large numbers and kind of growth rates in that business? Because sustaining a mid-double digit growth rate in a business that's $1 billion is a lot different than.
Yeah, well, thanks for having me. And yeah, we had a great Q3, and it's great to see you guys. Maybe just a couple of highlights. As you mentioned, we had an outstanding revenue performance in the quarter, cresting above $500 million, I think, for the first time in the company's history. We grew yet another record clinical signature units. We were, once again, north of 20,000 just growth units in the quarter, 200,000 clinical units overall. An outstanding post on gross margins. We did about 64.9% gross margins. And then if you back out true-ups, I think that was 61.3%. So, both of those, both organic and kind of printed gross margins, were records for us. Really, it was kind of an outstanding performance kind of across the board. Women's Health performed extremely well.
Organ Health continues to be on an absolute tear for us, and we're very excited about that. So, this is year 10 for me at the company. And as I often tell folks, I'm the relative newcomer among our management team. The rest of the team has been here longer than me, but I just don't recall a time when we've been in a better position. We've had better momentum in the business. As it relates to growth going forward, you've got a couple of different businesses, and we laid out on the Q3 call, I think, how to, it's an initial framework on how to think about growth and how to think about margins, at least going into 2026. And so, let me break those down just briefly.
The way we've always thought about growth is not based on growth rates, but we just think about this based on absolute growth units for the business. And the reason why we think about it that way is that we really build our forecast bottoms up based on what we're seeing from the sales team. The sales reps for Organ Health and for Women's Health are remaining relatively stable, as they have been stable for quite some time. And so, I think about that as, hey, can we grow the same number of units in 2026 as we did for 2025? I think that's an initial framework to think about how that team can actually grow the business in terms of volumes. ASPs, my initial read on that would be to have ASPs stable for both of those businesses.
And both Women's Health and Organ Health, we've had fantastic ASP improvements, average selling price improvements over the last couple of years. For Women's Health, we went public in 2015, and I think that the ASPs for NIPT are actually better now than they were 10 years ago, which is quite an achievement for a diagnostics company. Usually, you have that trend going the other way. And it did go the other way for us for quite some time. And just in the last two years, we've been able to, through a big investment and a lot of execution within the company, we've been able to really increase the percentage of time we get paid when we've offered a covered service.
When NIPT is covered, we've been able to jump through the hoops and manage the bureaucracy in a way that allows us to actually get reimbursed for that test that is covered as per the coverage policy. Similar story in carrier screening. Carrier screening ASPs are also looking quite strong. So, I have historically thought about the Women's Health business in the last couple of years. Those two things imply kind of mid-single digit growth on volumes, low to mid-single digit growth on volumes, and slightly faster growth on revenues, just as we continue to get some improvement from ASPs. I think an initial framework for 2026 is just, hey, hold them stable and see how we do. Organ Health, again, the ASPs have been phenomenal. The reimbursement has been quite consistent there.
I think that business is undergoing a very positive change, where we've had now, cell-free DNA has been offered in the organ health space and kidney transplant rejection space now for five to seven years, I guess. And so, there's been time for us to put out some very long-dated outcomes trials now that show the efficacy of the cell-free DNA, even as compared to the traditional tissue biopsy. I think the cell-free DNA just continues to perform so well that I think you're kind of undergoing the sea change finally, where the cell-free DNA is going to start to supplant the tissue biopsy, and that's sort of a secular growth vector within the organ health space.
In oncology, I think it's a little bit of a different way to model just because of the size of the MRD market and how early we are in terms of the penetration of that market. So, we've just kind of thought about these growth units every quarter. What's a reasonable kind of expectation for growth units in a quarter? And what we mentioned on the last call is just maybe think about just the rolling four quarters average of the last four quarters of growth units. That would have implied about 18,000 units in Q3. I think that's also a reasonable jumping-off point. I mean, that's not a low bar, and I would fully expect there to be quarters where we're above and below that.
But if you're willing to back out to the scope of a one-year lookback, I think you can see a very kind of linear upward trend in MRD volume growth, just because, again, we're so early in the penetration and it's such a massive unmet need. Pricing for Signatera, I think there is plenty of scope to continue to grow the realized pricing through the same dynamics I was just describing, just improving kind of the fraction of time we're covered for covered services. And also, as we deliver more data, eventually kind of getting more broadly into clinical practice guidelines, so I know that was a lot, but that was sort of a recap.
I mean, I think you kind of take the different call points where we're leaders, and then you build it to something that I think is, I think the growth kind of continues in a really strong way into 2026 and beyond.
All right, great. Thank you. So, we've done a ton of doc checks, and one of the things that we've kind of been finding of late is running Signatera early and often, particularly in the adjuvant and neoadjuvant setting. Now, you've broken down some of the numbers of something like 10%, 15%, 20% first-time tests, but I think you've also said 50% of tests are in the adjuvant setting. It kind of implies that docs are frequently testing in that adjuvant setting. So, how many tests are you seeing being ran on average in that setting?
Yeah, what we've seen over time, and it's been relatively consistent, is patients are getting something like four tests in the first year and then two tests in the intervening three years or so. So, roughly 10 tests per patient over the course of their journey. And that implies the adjuvant window is something like six to nine months for people. So, what we see is there's two and change tests in that adjuvant treatment window, two to three tests in the adjuvant treatment window. That hasn't really moved all that dramatically, really, over the last five years. That kind of meets the clinical workflow that has already been established for patients getting adjuvant treatment.
As we move on to a little bit more aggressive cancers, do you think in that adjuvant setting you could see more volume? I mean, we have talked to docs that say with aggressive cancers early on, we do like to run every six weeks. And I think in IMvigor, [crosstalk] you actually did have an every six-week.
Yeah. Yeah, so IMvigor is a good example of a more frequent testing protocol that was used in the study to great effect. I think that the testing frequency will, of course, vary by tumor type. I still think that when you back up and you think about what is the average across all the different tumor types, I still think that that framework is the right one, about 10 tests over the course of a patient's journey. But certainly, we've seen a real, anecdotal, of course, but we've seen a real uptick in demand among physicians who just want to replicate the IMvigor protocol when dealing with muscle-invasive bladder cancer. And I think that's a very compelling use case for Signatera.
All right, thank you. Can you remind us in terms of, I mean, I know that private payers is not the majority of tests right now, but as you go and you get into contracting with more private payers and Signatera, how are you going to think about pricing? Are you going to think about the bundling pricing upfront? Are you going to think about the ADLT surveillance rate? I mean, how are you thinking about that as you're contracting?
Well, I mean, the good news is that for the vast majority of covered lives, I mean, we're already a large in-network lab for most of these big payers. And many of these large payers have very meaningful Medicare Advantage books, where they provide the Medicare benefits and Medicare beneficiaries on behalf of the Medicare program, and it's a services offering for the payer. So, as we've gone through this journey, we've gone and obviously gotten a lot of coverage from Medicare, and that has caused us the need to go and then contract with the payers to get the Medicare Advantage patients covered. So, if you have some large payer, I've got one big omnibus in-network contract with that payer, and page four of that contract lists out all the Women's Health products. Signatera is one of the rows.
And then next to Signatera, there's a negotiated price, which has been a function of the reimbursement, the pricing we've already established with Medicare. So, there's not necessarily an immediate need to go around and redo the contracting discussion as coverage broadens and as we get into guidelines. Over time, I mean, I think those types of conversations do happen, and it's kind of a continuous process. I mean, these in-network contracts we have with the payers are kind of evergreen contracts. And so, it's a conversation that we have with payers.
Our goal there is to work collaboratively with the large payers, where we want to make sure that we're delivering kind of very obvious clinical utility, where we are obviously delivering a great benefit to the physician and the patient, but also that the savings that we take out of the system with our result is so clear that our reimbursement is really a function of the savings that we generate for the system. I think as long as that's your framework, I think we've been able to show that you can have very consistent pricing and a collaborative relationship with the payers.
Gotcha. Can you remind us of some of the submissions for reimbursement? I think you've mentioned seven. And MolDX, at a certain point, are going to have to give you a pan-cancer coverage. I mean, I would assume at a certain point in time or a submission type, I mean, it's going to be advantageous because you're not going to be looking at these highly rare cancers, right? So, I mean, just how do we think about that?
Yeah, well, we've talked about this. I mean, one of the surprises for me is the breadth of tumor types within the volume mix of Signatera. I would have guessed a couple of years ago that the vast majority of the volume would have centered on kind of colorectal cancer and maybe breast cancer because that's where a lot of our early data was in the case of colorectal cancer, and then breast cancer is such a common disease in the U.S. What's happened instead is that the mix of tumor types has remained relatively broad and consistent, even as the business has grown substantially over the last couple of years.
I think what that indicates is that physicians are getting the tool, the Signatera tool in their hands, and then they're generally kind of adopting this fairly broadly within their practices, such that if they have a head and neck or esophageal cancer patient that comes in, they end up offering Signatera to that patient because the data has been quite uniform across tumor types, and it works in kind of a very similar use case across many solid tumors. What that means is that there's now a pretty meaningful chunk of Medicare patients that have a cancer type where we haven't yet gone to Medicare and actually gotten coverage in that tumor type. We're in the process of a fairly large effort of just getting another set of expansion of coverages across more tumor types.
I think we said on the call that we've got something like data for seven submissions to MolDX that are more or less ready to go. And so, the dialogue about the breadth of the coverage with MolDX is something that will continue to evolve, I think, just given the above dynamics. I think the base case for investors and our base case is that we just continue to do the thing that we've done, which is to work collaboratively with the MolDX program, show the clinical utility, and just get covered tumor type by tumor type. That will yield, I think, a meaningful opportunity to improve ASPs, consistent with the data we've been able to put up.
I maybe ask a couple of questions on IMvigor. I think you saw, what is it, 41% improvement in overall survival. Can you talk about the biology of bladder cancer and why you're able to show that here? And if there are other tissue types that might have kind of that similar use cases, bladder cancer?
Yeah, I mean, maybe just a quick recap of the IMvigor trial. Roche Genentech had a drug that's on the market in a few indications called atezolizumab. They were running a phase III clinical trial to evaluate atezo in muscle-invasive bladder cancer, which they had enrolled as a phase III trial, adjuvant, MIBC. That first phase III trial, IMvigor010, actually, I think that kicked off before Signatera existed. I mean, I don't think that we were on the market. I think we were on the whiteboard in San Carlos kind of dreaming this thing up. But before they read out the results, we had Signatera in the market. We'd had some very compelling, if initial, data.
Before they read out IMvigor010, they pre-specified an endpoint to say, "Okay, we've got the primary endpoint is efficacy in all comers, but let's look at treatment response just among the Signatera positive patients as kind of a secondary endpoint." Unfortunately, in 010, the drug did not work on all comers, did not meet a p-value in all comers, but they had a fantastic treatment effect just among the Signatera positive patients, okay? So, and this was 2020, 2021. This has been a little while. That was a hugely important readout for Signatera. We rushed around with Roche to enroll a second phase III trial where entrance criteria is being Signatera positive. So, patients then in IMvigor011, muscle-invasive bladder cancer patients are getting serially monitored with Signatera.
And then when they turn positive, now they're getting randomized plus or minus atezolizumab, and we're going to see how they do. The results were absolutely phenomenal. I mean, the study was powered to generate a disease-free survival result, and we had an overall survival signal. The data was published in the New England Journal of Medicine. I think one could argue that really represents a sea change for the treatment of muscle-invasive bladder cancer. Lots of implications to kind of pull out of that summary, and that's why I wanted to kind of give you that background. Just for example, patients that were getting serially monitored, perhaps they were positive on the first test, and then they got immediately randomized to the plus or minus drug. Those people had a fantastic result, just as you might have expected from IMvigor010.
Now, you also had a cohort of patients that were negative on the first test. Maybe they were negative on the second test, and they turned positive on a subsequent Signatera test. And then they're randomized to the drug. So, this is an open question. How do those patients do? Okay? Do they pay some kind of price for effectively delaying their treatment until they turn Signatera positive? And the answer is no. In fact, those patients actually did better, and it's probably something to do with kind of their risk category of their disease. But there was no penalty paid there. I mean, those patients did fantastically well. So, lots of implications.
I mean, you have the obvious implication of, "Hey, how do you treat bladder cancer patients with this?" And I think you heard on the podium from physicians at the ESMO conference. There's a lot of physicians that feel like this is a real change for the way that bladder cancer gets treated writ large. I think we're starting to see that come through just in our kind of anecdotal kind of interactions with the community. There are a ton of different tumor types where data like this is going to be extremely valuable, and it's going to be replicated. Not like exactly the same way that the IMvigor study was run, but just, for example, at San Antonio Breast, we had some data from the LEADER study where patients were getting a CDK4/6 inhibitor, okay?
You're looking at, "Hey, patients, what about patients who were Signatera negative versus Signatera positive?" The patients who were Signatera negative and were not getting the drug did extremely well on extended follow-up. The patients who got the drug really benefited from the Signatera positive patients who actually got the therapy benefited hugely. You're going to see that type of data set come from us time and again, and we'll partner with pharma in a lot of different settings to expand on that theme.
Gotcha. I think you kind of answered my next one on IMvigor 011 and that one, but so maybe we can go to Signatera. I think there's not really a lot of holes to poke in the kind of competitive front here. One of the questions we do get from investors, though, is finding tissue, and specifically, does that give CGP players that do solid tissue any kind of access to kind of patients? And maybe I've seen the reverse of that. I couldn't help but notice, I think the oncology revenue was up pretty well, and then you give MRD revenue so I think I did notice Altera is actually growing pretty good. Does that actually give you maybe an in kind of to get more volume in CGP?
Well, I think that, I mean, obviously, the primary focus has been, what do we do to improve our MRD offering and what problems do patients and physicians encounter that we can solve or that we're very well positioned to solve by dint of the fact that they've started Signatera with us? I love that type of conversation because when you launch a test that we think is best in class, that gains a lot of traction on the merits of its data, you get to have that conversation with patients and physicians. Well, what other problems do you have? What else would be very convenient for us to solve for you? Oftentimes, at the same time point, same patients, what other clinical questions can we answer? We did that to wonderful effect in the women's health business.
I mean, we had what we think is the best in class non-invasive prenatal test, and then I think in the middle of 2015, we launched a carrier screening test, Horizon, to go alongside NIPT because we noticed that physicians and patients were at the early point of pregnancy. This was the time that patients were really interested in understanding what is their kind of background carrier status, so we were able to offer the Horizon test on the same rec form, another checkbox, and that was a huge benefit to patients, so we were able to really grow kind of a second product alongside the flagship non-invasive prenatal test. I think there's a lot of opportunities to do that with Signatera and answer additional clinical questions. You mentioned Altera, the tissue CGP. I do think that's growing.
And there's a growing set of physicians that want to understand the tissue genomics more broadly while they're ordering Signatera. So, I think that's a very significant growth opportunity. And there's a couple of other clinical questions that over time that we aspire to answer as well. So, lots of kind of ancillary opportunities alongside Signatera.
Gotcha. We only got a minute and a half left, but I do want to squeeze in some. PROCEED, kind of what are the next steps in the program? What can investors expect from a commercial launch and revenue contribution from ECD? Hopefully, I can get a Prospera and an expansion question in, but we'll see. Probably not.
Yeah. Sorry, I'm trying to go lightning round. So, PROCEED. So, we were very excited to read out some results from the PROCEED trial where we were very focused on delivering a preliminary result for our test performance in advanced adenomas. We prospectively enrolled 1,400 patients in the exact intended use case, exact same protocol as we'll use in the FDA-enabling FIND study. Out of those 1,400 patients, we got back 93 advanced adenomas, and we performed extremely well. I mean, the sensitivity of the test was circa 22%. Importantly, the one standard deviation was 15%-31%. So, I think anywhere within that zone, I think that represents game-changing test performance. I think that can be really important for patients and physicians that otherwise just don't get screened. I mean, there's 40 million unscreened people. The next update really is going to be the FIND study in 2027.
And error bars around the exact timing of the readout of the FIND study. I mean, you just got to enroll patients, and there's all the normal dynamics with a clinical trial. But we're just going to go full speed ahead. We're going to make the investments necessary to accelerate that as best we can.
All right, well, thank you very much.