We're lucky to have with us Mike Brophy. Mike, welcome.
Hey, thanks for having me.
Mike, I'll start off. You just reported Q3 results. I'd ask, perhaps you can reflect back on performance and what were the highlights?
Yeah, I had a very strong Q3 result, $592 million in revenue. That's year-on-year growth of 35%, which is actually faster than what we've grown in the year-on-year over the first couple quarters of 2025, even though the business has continued to ramp. I mean, the comps get much, much tougher, and yet the growth rate was still higher. Another kind of fantastic volume quarter, really across the board. I'd call out Women's Health had a very strong kind of sequential quarter, as we'd hoped and expected. Organ Health continues to just be on an absolute tear, and then you have the Signatera results, so 202,000 units in the quarter. Fastest growth, sequential unit growth quarter ever, 21,000, so 21,500, so a big step up in Signatera. That implied another massive quarter for new patient starts and a continued drumbeat on people staying with us through recurrence monitoring.
Gross margins were excellent in the quarter. 64.9 was the printed gross margin. Again, it was the best ever. 61.3, ex the true-ups, so very strong, more than 100 basis points. I think it was like 120 basis points sequentially, kind of more on the organic gross margin improvement just over Q2, so continued to have very lean COGS and continue to progress on the ASP front. On the clinical side, of course, we had some amazing data at the ASCO Conference. We had data that was published in the New England Journal of Medicine. Very proud achievement for us. Prospective interventional outcomes trial in bladder cancer with Signatera. I'm sure we'll get more into that. Partnered with a drug that, unfortunately, did not meet its primary endpoint when evaluated in IMvigor several years ago, 2021, I think, 2022, something like that.
And then paired with Signatera, had a fantastic treatment effect. Actually delivered a positive overall survival result, even though at this stage of the progression of the trial, we're really only powered for a disease-free survival outcome. So very, very strong result there. Strong result across the board, across a range of different data sets at ASCO. Very good momentum that we've seen so far in Q4 across the board. On the guide for the year, we were able to kind of massively kind of step up the revenue guide, bumped the gross margin guide once again. And then on the bottom line, we'd said previously that we hope to generate free cash flow through the course of the year. And we bumped that guide to we think we can generate about $100 million in free cash flow for the calendar year 2025.
So that should give you some confidence that even as we continue to just pour investments in to grow the top line, that we're really getting scale on the business. So I'm really happy. As we've talked about, this is year 10 for me here, and it's a lot of the hard work that we've been putting into this business over a period of time is really bearing fruit right now. We've got a very exciting kind of 2026 setup, so.
A lot going on. Let's start off trying to unpack that Signatera sequential ramp, if it's even possible, right? I mean, you've had a lot of different announcements over the past 10 months or nine months, which could have contributed to that sequential acceleration. When you talk to your reps, what do they attribute the strength to?
I think that it's interesting. I think it's hard to ascribe the success of Signatera to one particular driver. I think it's really kind of the confluence of events. I mean, one is the operations are really humming. So in terms of people's turnaround times, their ability to kind of get the result when they need it, kind of in the flow of their kind of typical clinical decision-making, that is, we're just really firing on all cylinders there. So very pleased to see that. I think the reps have continued to progress in terms of their ability to describe all the different ways in which Signatera can deliver clinical utility. One of the ways that they've been helped in that is that we have had a drumbeat of amazing clinical trial results.
One example from earlier in the year was this Celebrex data that was presented, I believe, at ASCO early in the year, where maybe I'll just give a quick summary of that. I mean, I think the presumption among physicians in the field is that a lot of patients with stage III colorectal cancer, they have this polyp development in their colon because they have some kind of inflammatory cascade that's gone awry. And so it makes sense if you knock that down with an NSAID that you ought to be able to help these people. And yet when the prospective study is run, frustratingly, the mechanism obviously is multifactorial and it doesn't actually work on all comers.
Okay, but you know that it has to be working on some people, but you can't just give it to everyone absent that data because there's a fear that you will kind of create bleeds for these patients if you're kind of chronically dosing them with Celebrex, for example, then you just rerun that study, very similar setup to this IMvigor study I just described, but now you just parse the patient population by who is Signatera negative and who is Signatera positive, and when you just look at the response to Celebrex among the Signatera positive patients, there's a wonderful treatment response. Okay, so that's a very practical, easy-to-understand use case for using Signatera to help triage your patient, help manage their journey.
And I can't prove this to you because there's a bunch of different data sets that have also been amazing, and the team has been kind of congealing quite nicely. But I personally think that that's an important driver for why we had record new patient starts here in Q2 and Q3. So that's just one example. It's important to kind of continually have this kind of drumbeat of data, which, rewind five years ago, you'd hope to have one readout like that per year. And now, because we've been continually investing in the development of the evidence, now you kind of this IMvigor data, we started working on this in 2018, 2019, and now it's reading out. So almost every major conference that we have will have kind of a drumbeat of very interesting data sets that can continue to highlight the utility of Signatera in the field.
Got it. And you opened up talking about your operations. So can you quantify turnaround time? Where has it been? Where have you taken it to as a contributing factor?
Yeah, I mean, the most common turnaround time is for the plasma test. And that's, I mean, you're within the window. I mean, you're within typically a week of order to getting the result back, which fits in nicely with the clinical workflow. For the initial time point, you're kind of inside that, call it, month to three weeks error bars around that. But that fits in very well with when the physician needs to engage with the patient on the next step in their journey. I mean, typically a patient will have a surgery to have a tumor removed, and they don't decide, "Oh, I'll keep it therapy within the next couple of days." They go home and rest. We see how they're doing. There's evaluation of the tumor in the pathology lab. There's all kinds of other kind of clinical workflows going.
But then you have a follow-up meeting with the patient, call it 30 days out. And it's nice to have the result within that kind of decision-making window. And we're well within that clinical decision-making window the vast majority of the time, we're finding.
And were there times in the past where you weren't and that's incrementally improved?
I don't think, I mean, we got to a place where these turnaround times were pretty tight and within this decision-making window reasonably quickly. Of course, I mean, you rewind five years going back to the launch. I mean, this is something that's hard to get right, kind of right out of the box. And so we've had to make very significant investments in order to get that whole operation going. I mean, and you probably recall this. I mean, one of the main pushbacks that we had when trying to raise money to create this new category of cancer care was that this is too hard to do. It's too hard to execute. It's going to be too finicky to get the tissue from the path lab and build a personalized test for each cancer patient. No one's ever done that before.
So leave aside whether or not it'll work, you just won't be able to execute it. And so showing now that we can execute this at scale, I think is absolutely critical to bringing the technology and bringing the utility to a huge set of patients. And we can clearly do that now.
How would you describe the trend in rep productivity?
Yeah, I mean, I think one of the interesting things about rep productivity in this space is that we, unlike any other diagnostic tests that we've offered or I've been associated with, you do have an ongoing relationship with each of these patients in a way that you don't quite have to the same level of that in other areas, like in Women's Health, for example, where this is a repeat monitoring test. Okay, so you deliver a result, and you're going to interact with that patient again three months later. And so there's an element for the sales rep where the service itself has ongoing utility. And so that tends to enhance the rep's productivity because they're really a service provider. I mean, they're like a problem solver for the office rather than like a traditional sales rep.
I mean, they're there to provide information and make sure the service is working as expected and to coordinate questions and things like that more than they are trying to make sure that the doctor ordered the test. The ordering patterns and the volumes are really flowing to us as a function of people's kind of emergent need for the test versus like a sales rep, sales activity per se.
Got it. Okay. And what feedback are you hearing from your team on the competitive environment and your competitive win rate for Signatera?
Yeah, I mean, for the full kind of five years that we've been in the market, there have been very impressive companies that are vying to offer their own solutions. I think particularly once we showed that this market can exist and this can be an incredibly important kind of category of cancer care, we saw an influx of competitors in the 2020, 2021 timeframe. So competition is nothing new. And I mean, it's to be welcomed. I mean, it's good for the system to have a bunch of different companies, smart people trying to come up with incremental new ideas or new ways to help these patients. So that's been fantastic. In terms of the competitive response, I mean, it's not even really how we even think about it.
I mean, we just try and just lock in on what are the use cases or unmet needs that the physician and the patient have and just really try and be as aggressive as we possibly can be in trying to solve those problems for the patient and the doctor, right? And if you're doing that, the competition question kind of takes care of itself because you're always going to be running into other companies that are also trying to do that as well. So the result of that so far is that it's been relatively muted in terms of other players generating meaningful volume. I don't expect that to be the case forever. I mean, I think it's just too important of a use case. I think there's lots of interesting companies that are trying to do interesting studies and things like that.
I think that's all to the good. I don't think that is harmful to our investment case whatsoever.
Has your team had to play the Signatera genome card to any meaningful degree?
I mean, again, I mean, it's not like a card that one has to play. It's something that's part of our offering, and it's something to let physicians and patients know about if they'd like to avail themselves of the genome, and there's arguments for and against, and every physician has got to kind of make that decision with their patients, so it's something that we're very happy to offer and proud to offer. The early data looks amazing on it. It does not have the same level of validation as the exome, and nor could it because, I mean, we just launched it fairly recently. I think what's more, the trend is less about having some opinion about one aspect of the workflow or another and just wanting to order Signatera, so if we updated our PCR primer design, that could potentially have implications for assay performance.
And yet you'd never have physicians or customers really worrying about what version of the assay or the PCR primers they're getting. They're just getting Signatera, right? And it's kind of backed up by that data. And I think that's kind of similar whether it's exome or genome. People just want Signatera. It's priced the same. So I think it's interesting because I think investors, because of the companies that are available for them to diligence, they want to zero in on the sequencing backbone. But there's a million variables that affect performance that ultimately you just got to prove out with data.
I don't anticipate I'll be diligencing PCR primer design.
I would welcome it. I mean, I make that one up, but I mean, improvements to the algorithm. I mean, it's something that we care about. It's something that we monitor and we learn by watching outcomes for patients as they flow through our system. Hey, we may not understand mechanistically why one potential improvement to an algorithm might be advantageous, but it looks like it would be. We make the improvement. That's a way for the product to continuously improve. That's what we love.
You mentioned you've had a couple of record quarters now of first-time patients for Signatera. Can you bring us current on what proportion of your Signatera volume is first-time patients versus recurrent customers?
Yeah, I think this number would be variable quarter to quarter. For example, in a given quarter, something like 10%–15% of the total volumes are typically initial time point patients. And sometimes it's 15% and sometimes it's 10%. And I honestly think that there's just a little bit of randomness in there just because it's not a huge number as a percent of total. And it's just the vagaries of the calendar or when people showed up. I think that the total volumes are kind of instructive of what's happening. You see them ramping. And that's a function of two dynamics. One is obviously you do have a continual flow of new providers and new patients coming kind of into the top end of the funnel, if you will.
And then because we're doing a good job for these people, there's an interest in staying with us and having multiple Signatera tests delivered over the course of their cancer journey because the Signatera test can answer different questions as you progress in your journey. So you got to have very high, we want to have very high kind of continued ongoing volumes with patients for whom we've gotten them started on Signatera. And we've got to continue to deliver data and make the arguments to physicians and patients to have more and more people adopt the test. I mean, we've quoted this stat historically, but I think the last time we quoted it was like a little less than half the oncologists in the United States, we estimate, had ordered a Signatera test in the last quarter.
That number, I think, can continually go up so long as we're just continuing to deliver data and continue to show people what the utility is of the test.
Okay, so there's nothing proportionally changing between first-timers and recurrent. It bounces within a band and is part of the overall trend.
Yeah, I think that from my perspective, it bounces within kind of an expected zone so far, quarter to quarter, and I think that you will have occasional quarters that are outliers, and then you see it kind of come back in the next quarter, so I've been very pleased with that. The total number of new patient starts obviously keeps going up. I mean, and you can see that in the total, the volumes keep going up.
What about your mix between adjuvant and surveillance? Where does that stand?
Same answer, and it's really a function of these same dynamics. You know what I mean? It's a function of that, I think, for modeling purposes. I mean, I think historically we've talked about the adjuvant treatment volumes being about half of the volumes and the recurrence monitoring volumes being roughly the other half. That will also bounce around quarter to quarter. When I'm trying to model this business, I try and think about it as being roughly proportional. Over a longer term, one would expect, just given the momentum of the math of people staying with Signatera over the course of their cancer journey, one would expect the mix to shift more and more toward recurrence monitoring, so I wouldn't be surprised if that happens.
If anything, we try and forestall that with all these activities I just described to make the case for new cancer patients starting with us at the beginning of the journey. Sure.
And then one of the things that struck me from your IMvigor presentation was the disclosure that in muscle invasive bladder cancer, you have less than 10% penetration. What is that penetration figure across your bigger tumor types, colorectal, lung, breast cancer?
Yeah, well, so to calculate a penetration, first you need a denominator. You need some kind of estimate of the total addressable market, and here, I think thoughtful analysts can come to different numbers, so I'm not trying to ascribe like, "Hey, this is the right number." I'll just share how I think about it, and I think reasonable people can have different takes on these variables. One is what is the incidence rate of a cancer. Let's just do in the United States to make it easy on me. I think that the incidence rate for colorectal cancer, for example, is something like 200,000 new patients a year. Then you need to make an assessment of what fraction of those patients are relevant to Signatera. I would argue that a very high proportion of those patients would have a disease that is relevant for Signatera.
Maybe it's 150,000, just again, rough justice. If you came up with a different number than that, then I wouldn't necessarily push back. Now, it's a repeat test. It's not just a one-time test. How many tests are patients going to get over the course of their journey? We're seeing on average that they get about 10 tests over the course of their whole cancer journey. Once you have enough years of patients starting on Signatera, if you think about what my quarterly volume is, a blend of all these different patients that have started using Signatera at different years. Okay, so it does start to look like a waterfall if you think about kind of building the volumes on an Excel spreadsheet.
And over time, I think we're kind of there now. You can start to sum the columns, right, which are kind of the years, and you also get to about 10. Okay, so also because I like to have easy math to do, I think about taking the incidence rate, assessing what fraction of the patients are relevant to Signatera, and then just multiplying that by 10, not as like an iron number, but just like a rough directional justice of what the TAM might be for volume TAMs every year. So that, in my example, that would be 1.5 million tests per year. About half of our volume is CRC volume these days, roughly half. So that would have been 100,000 in the quarter. So run rate that, which kind of overstates where we are, but just to be conservative, let's run rate that.
So that's 400,000 a year on 1.5 million. That's about where we are. And that's by far the most penetrated tumor type. I mean, breast cancer is nowhere. So I think the other tumor types are very, very small. And the net of all that is kind of the single digits penetration that you've heard us talk about previously. Just in colorectal cancer, I would also point out we're pursuing FDA coverage in Japan, which would effectively double the number of patients that are available to us as a TAM for colorectal cancer. So still very early days in this market.
Sure. And sorry to make you do math on stage. I love it.
That's why we picked 10. That's why we do the, you know what I mean?
But to use your example of 10, most of those are surveillance. And if we think about your volume mix being 50% adjuvant, 50% surveillance, I think it's possible to come up with some math that suggests that the adjuvant CRC is far more penetrated. Do you have any thoughts on that math and its implications?
Well, I think that what that would be is like a leading indicator for the total TAM, and so that would kind of augur well for the total volumes kind of continue to go through. I think that we deal in a number of markets, like I'll give you an NIPT as an example, where the market is probably 75%–80% penetrated, and yet there's still plenty to do, right? You have to kind of get to this kind of 70%-80% penetration level in our experience before the total TAM even really becomes a consideration in terms of what you would model for future growth.
I'll just tell you, having just been an executive in the space for a long time and dealt with a market that has gone from very low penetration to now with an NIPT very high penetration, with colorectal cancer in particular, we're very much in the early category where it's more a function of like, "Hey, can we get enough commercial people in the field to offer this to more people?" I mean, that's very much more the mindset versus like, "Oh gosh, is there going to be a slowdown?" I think that's really premature. I mean, I think you're years and years away from that.
Okay. Another topic from the call I wanted to touch on were the seven additional Medicare indications you plan to file or submit to MolDX. Can you talk about that? That's a lot for one year. And pros and cons in submitting seven versus wrapping them all up in one big package and going after pan cancer.
Yeah, well, I think that's a possibility, that you end up with a pan-cancer, just a pan-cancer coverage. I think, the way whether or not you get coverage in a pan-cancer setting or you get individual coverage decisions for seven different indications, you kind of get to roughly the same place in terms of the tumor types that are covered. So I'm not hugely stressed about one outcome or the other there. And by the way, we feel very strongly that if you expect physicians to order this test in these different tumor types, many physicians want data in the specific use case, in the specific tumor type where they're ordering. And so we feel like it's very important to deliver this data across a very broad swath of tumor types for now.
I think over time, what we've shown is that the data looks very, very similar across a bunch of different tumor types, and so I think one can start to get some comfort that this works reasonably well in a generalizable way, understanding that different cancer types are different. They get treated differently, and tumor-specific data will always be part of the hallmark of the package that we offer.
Okay. Well, let's migrate over to IMvigor. As I mentioned to you yesterday, I re-listened to the webinar, and it struck me how bullish it was. I think Alexey made a comment, category defining, broad implications beyond muscle invasive bladder cancer. Gosh, that's hard to put into a model. How are you thinking about that?
I mean, I think we're very proud of the data. We're excited to be able to partner with Roche, an important clinical trial. I think that what we've seen historically, and I gave you the Celebrex data as an example, which didn't have anywhere near the level of acclaim that this IMvigor data has, is that it does, I think it has historically been a call to action for increasing numbers of physicians to consider integrating Signatera into their clinical practices. So it wouldn't surprise me if that becomes its own call to action, its own driver as you go into 2026. I think some of Alexey's comments just reflect the fact that this data just hasn't existed before. This prospective interventional overall survival data, that's outcomes driven, is very hard to do.
Again, we started working, I think, on the initial IMvigor study before the pandemic, 2018, 2019. Here in 2025, now we've got outcomes data. It's a statement about the time on task that's required to deliver that level of evidence and how important it is.
Okay. And it seems like there's a lot of interest in de-escalation work as well. You've got a couple of questions on that on conference calls of late. VEGA is going to be a 2027 readout. Do you have anything in de-escalation which could read out sooner than that?
Well, there may be. I mean, I think there's an element of the IMvigor data that also speaks a little bit to de-escalation. I mean, what was interesting. There are many things that were interesting to me about that data set. One of them was, and again, the trial design is enroll patients into the trial and then serially test them with Signatera. And when they turn positive, then you randomize them plus or minus the drug. Okay, not everyone turned positive right away. Some people turned positive at the second or third time point, just for example. Okay, so an open question might have been, "Hey, how did those patients do relative to patients who were positive right away?" And what we saw was that they also had an outstanding benefit.
So they didn't really pay a penalty for waiting to commence with the randomization and getting the treatment because they were Signatera negative. That tends to comport, I think, with the judgment that you can be without cancer and then you can have a relapse that's relatively rapid. And so long as you're on it when the patient relapses, you can really have a positive impact on their care. So I think that is, I thought that was hugely interesting data. You're right on the timeline for VEGA. And I would just caution you that that's an events-driven trial, right? So the design for that is you have patients who are Signatera negative and they're being randomized to get kind of standard of care treatment. And you've got to wait for events there. And so what I would hope is that the Signatera negative patients are extremely healthy.
So it should take a long time to get enough events to calculate the statistics to read that out, right? So that's an important consideration. And so we'll see when that actually reads out. I mean, it's actually not within our control to tell you that it's due on a certain day. We just have to wait for the events. I suspect that there will be other data sets similar to what I just described with IMvigor, and there have been many others where there is data that you could look at that kind of sheds some light on the utility and de-escalation.
Okay. We're going to have to be rapid fire here.
Good.
To move on to your efforts in cancer screening, should we expect any update prior to 2027, whether it be for your colorectal product or more color on your efforts in multi-cancer?
Not planning on it. I mean, opportunistically, if there's data that we're going to submit to a conference, of course we'll share it. But really the plan now is just to run full speed at the FDA readout. We feel like we got what we needed from this interim result in terms of giving ourselves confidence in the investment case for the product. We think this can be a very important product for the field and for the 40 million people that just remain screened for colorectal cancer that should get some form of screening.
Okay. So no more marker trial and error?
Well, so in terms of the assay development itself, we'll continue to work on the assay up until it's time to read out the data as is typical. I don't anticipate us having multiple different analytes or a massive change to the assay between now and when the readout is, the final readout is. And so I hope that that will lead to some stability in the results.
All right. Organ Health, I think 60% growth last quarter was driving that. That's far in excess of the market.
Yeah. Well, I think the market itself is kind of going under quite an evolution there. And now I will stress that this is just me speculating on this, so you're going to have to just take this with a grain of salt and do your own diligence on this. But it used to be that most pregnant women would get a quad screen, okay?
Organ.
I know. I'm going to get there.
Okay.
Yeah. Most pregnant women would get a quad screen. And the quad screen would be for every 20 positives, you'd have one true positive. All 20 of those women would get an amniocentesis. There's a lot of amniocentesis volume, okay? Now the NIPTs as a class are so good that, I mean, the number of NIPT positives matches over very tightly with the number of true positives. A lot fewer amniocenteses need to be run, such that if you need to get an amnio, it's probably best to go to a teaching hospital and go get that done because that's where there's enough volume to teach the residents how to do it, okay?
There's a similar dynamic I would propose to you in the organ health setting, which is the standard for confirming how a patient is faring post-transplant is to do a physical biopsy of the organ that you just transplanted, right? Not ideal as a form factor. I think the data that we've shown, particularly more recently in heart, shows you that the self-reading tests are so good, the Prospera test is so good that there ought to be an evolution, in my view, toward having that be the primary way that you screen these patients, which obviously expands the, it doesn't expand the number of people that are getting transplanted, but it does expand kind of the use case, I would argue, for the assays in the field. So I think we're kind of, that's underway.
The other thing that's happened there is that we've just executed our standard playbook with excellent customer service, excellent user experience. We've spared no expense in delivering the highest quality prospective data set that we can deliver. The results have been excellent, and we are offering this to a set of patients and physicians that have a dire need, that have an emergent situation ongoing. They're getting a kidney transplant. They want to know how things are going post-transplant, so you have that kind of demand pull from the patients and a desire to get things right, so that's a very favorable setup to us because of our kind of core strategy to deliver the data, and the data has been fantastic, and so the volume has come our way.
I apologize in advance. I don't think we're going to have time to talk about women's health, which is the biggest part of your business. But let's move on to margins for a moment here. It's hard to know how to model your gross margin cadence given all the true-ups. How are you thinking about that?
I normally think about the gross margins on that organic basis. So that's why we give that every quarter. So we strip out the true-ups and we tell you what the gross margins would have been if the true-ups had been zero. We give you both numbers, okay? So the 64.9% is the gross margin inclusive of the true-ups, which does represent good execution from us. And I mentioned on the call that October looked like kind of the best cash collections month we've ever had in the company. So very excited about that. Those trends in terms of collections seem to be continuing to progress. But I agree with you that the true-ups can be volatile quarter to quarter. And hence that top line number can be volatile as well. And so that's why we're at pains to kind of give you the true-up number every quarter.
So 61.3 is like if I'm modeling this business, I kind of build off of that organic number.
Okay. Why not just change your accrual assumption?
I think in order to do that, you just got to go through kind of a very standardized process. It's important to me that there's not too many areas of judgment in any of our accounting practices. I want to have a memo that clearly documents what the process is. And I want to leave that alone. You know what I mean? So that there's less volatility in that approach quarter to quarter. What has happened is that we have had now more than a year of outstanding collections and improvements in the rate of time we've gotten paid really across the entire business. So the longer that goes on, the more time that has to kind of flow into the assumptions of the accrual. So I think that's a possibility going forward.
We're out of time, but one more question I wanted to sneak in. The 10% growth in operating expenses, which you're framing for 2026, is that the new rate going forward? Or would you expect there to be some leverage on that figure in future years?
I mean, certainly over time, you will continue to get leverage on that figure because the absolute dollars matter when it comes to spend. For example, I mean, we're building, we made a big investment in the commercial team for Signatera. There's a finite number of oncologists in the United States. I can't just be continually making massive expansions to that. There's a natural level that that team needs to get to, and beyond which you're kind of doing kind of maintenance growth to it, while I would argue that the volumes do much better than kind of maintenance growth. So I think there's kind of natural leverage as a dynamic throughout the P&L.
Okay. Mike, thanks for your time.
Yeah, thank you for having me.