With Adaptive Biotechnologies, joining us is the CFO, Kyle, and then Susan is going to be here momentarily. There is an elevator slowness with the amount of people at the conference, and of course, in the audience also is Karina, so let's kick it off with some questions on kind of gross margins. You said a real big improvement in gross margins with the X transition. Can you talk about how much improvement you got in Q3 and what our expectation is for Q4 and beyond, and then is there any other levers to help with gross margins?
Yeah, I appreciate the question, David. With the X transition in Q3, we realized about 2% margin improvement, taking it from roughly 63%- 65%. We're anticipating still, and we've said this many times, 5%- 8% points lift over the next 12 months post-launch. All of those metrics are on track. We expect to continue to see increases in the first half of 2026 as we continue to grow volume as the most relevant driver of that. But we've got a ton of extra capacity with the X transition, so that's giving us quite a bit of tailwind in the margin profile of the business.
Yeah. Can you talk about maybe OpEx also in 2026, how you're thinking about balancing investments with kind of the, you just got back to, or you just got to cash flow break even, I believe, and so how are you making that balance?
Yeah, I mean, I think primarily on the OpEx front, it's continuing to press our advantage in things like EMR integration, looking for additional levers to either improve our reimbursement workflows, RCM initiatives, and continuing to drive the momentum and the growth we're seeing in the commercial business, especially in the community. That being said, we're going to continue to get a ton of leverage out of the business as we continue to grow, so I don't want to give any explicit guidance at this point, but I can expect some additional investments, but not a ton, and we will continue to get additional leverage as we continue to grow revenue.
And on to Susan, clonoSEQ is having another strong year. You had EMR integration, blood conversion, DLBCL as a newest tumor type, and readouts in multiple myeloma clinical trials. Can you rank order kind of what has been the largest contributors to growth?
Sure. You know, one of the things that's really nice and attractive about this business is that there are multiple things that are contributing at any given time. They're all actually interrelated and synergistic in many ways. So I think I'd probably rank EMR integration as the single largest contributor this year to accelerated growth. EMR integration is, of course, important not only for driving volume increase, but also for operational stickiness, which really helps us keep our position with our customers and create competitive moats. I think the second thing I'd probably rank is blood-based testing. We've continued to increase the proportion of MRD tests that come from blood, and that allows us to both increase frequency of testing as well as drive adoption in the community setting. Community growth is probably the third thing I'd rank.
We are continuing to steadily increase our penetration in the community, but we started with academic institutions, and so we have a long and high ceiling in the community setting, and one of the things that we have been able to leverage, it's been an important tailwind this year. Probably the fourth thing I'd list is guidelines, and we've seen improvements in the guidelines supportive of MRD testing in all five of our promoted indications this year alone, and I think there'll be continued traction in the years to come.
I want to focus maybe on the EMR integration, which kind of ranked one. Can you give us an example of some bigger account and volumes that might have happened prior to and after integration? And what is kind of the current EMR integration? And obviously, I'm not asking you to say, well, you know, at Mayo Clinic, we blah, blah, blah, but anyway.
Sure, yeah. Yeah, absolutely. So EMR integration, as noted before, is really important for a number of reasons. And we have now found that we've gotten a substantial proportion of accounts integrated that we're actually able to, beyond just driving volume, we're able to actually increase the consistency of testing. And that is an important use of the tools that are associated with the EMRs once they're in place. So a couple of kind of overview statistics. We've more than doubled the number of Epic integrations that we had in place this year. We also did the large Flatiron integration, which captured over 100 community sites. So we're up to now 165 total integrated sites as of the end of Q3, and we've continued to add more in Q4.
We are now seeing about 40% of our volume go through an EMR integrated flow, and we will continue to increase that number in the coming years. In terms of large accounts, six of our top 10 accounts are now integrated, and many of those were new this year. What we see in the largest accounts typically is a fairly substantial bump immediately post-integration, and then we see the growth normalize over time, but now off of a much bigger base. So it's been a really valuable tool in those accounts, increased access, more providers able to place orders, so it reduces the negative impact of things like staff turnover and democratizes access to ordering our tests across departments and providers.
All right, let's focus on that number two, the blood option. Are you finding test order? I mean, you already kind of said this, but can you give us some contextualization on frequency increasing due to blood? And how many of these tests the patients, how many of the tests, how many tests do you think a patient could have with a blood option versus having a tissue guide option? And maybe let's start with blood and then go to DLBCL in terms of what the differences in biology are and how blood impacts those two different indications.
Sure. So the frequency of testing and how blood can contribute is in part related to the disease biology, and each of the diseases in which we promote at clonoSEQ are a little bit different. At a high level, blood-based testing is, of course, important as a frequency play because bone marrow, which is the other main sample type that we test, is difficult to access. Most patients are not going to submit to a bone marrow draw more than once, maybe twice a year. And so enabling blood-based testing in indications that are traditionally bone marrow driven is really removing the governor from the possibility of more frequent monitoring, which physicians do like the ability to increase vigilance in between bone marrow draws or in the community setting where bone marrows are logistically difficult to get done and physicians are less comfortable doing them.
In that setting, blood as a potential replacement for bone marrow is really interesting to clinicians as well. So in multiple myeloma, where bone marrow is traditionally the testing mechanism because it's a disease of the bone marrow, blood carries less disease burden, but it's still a very useful complement to bone marrow testing. Our assay provides more information in blood than any of the existing traditional blood-based testing methodologies in myeloma. And if you get an MRD positive by clonoSEQ in blood, that's definitively correlated with disease in the bone marrow. So it's a really helpful rule-in test. So providers can do things like do a blood test first, and then if it's positive, they don't need a bone marrow. Or they can supplement bone marrow testing with blood in between to see if the relapse comes quicker than their monitoring schedule.
So in that testing setting, blood might be done every three months, whereas a bone marrow might be done every year. In the case of DLBCL, the biology is different. It's a disease of the lymphatic system, so most of the disease is found in the circulation. So that's why we're doing circulating tumor DNA testing. We're collecting blood in Streck tubes, isolating plasma, and extracting cell-free DNA. And so in that case, all the testing is in blood. And so we're not driving blood-based testing so much as driving market development, awareness of the unmet need in DLBCL, and encouraging that testing needs to take place. And there again, testing could take place conceptually every three months, depending on the point in the patient's journey.
Got it. You know, one of the things I always found interesting is the habits of physicians based on kind of the prior method. So even in solid tumor, kind of what we find is that a lot of physicians think about the three-month because that was where imaging was. And so if you're thinking about bone marrow, how are you changing physician behavior to maybe think about or teach them that they can actually test more frequently given the fact that it's kind of a change in paradigm? And is kind of that an opportunity to kind of get even more testing on a per-patient basis?
Yeah. It looks a little different if you're talking to academic clinicians versus community. So again, if we focus on these traditionally bone marrow-driven indications, myeloma, ALL, physicians in academia are thinking, I want to go to the compartment where the most disease potentially resides. So they're thinking bone marrow as sort of a default, and presenting data that demonstrates the high correlation between blood-based MRD by clonoSEQ and prognosis has been really important. We've also, in the context of ALL, shown that clonoSEQ is more sensitive in blood than flow in bone marrow. So that's been an important driver of conversion of academic physicians. In the community setting, we don't have to convert physicians because they're typically not wanting to do testing in bone marrow.
So there it's more of a question of, hey, does the blood provide enough insight beyond sort of these traditional tools like in myeloma, an M protein test? And we've shown data to suggest that yes, M protein, which is used to define conventional complete response, is not predictive of disease or is not as strongly predictive of disease outcome as clonoSEQ in the blood. And we've shown physicians that this can add insight to what they're doing in a normal setting and basically just add another test to a blood draw they're already doing to monitor their patients.
All right. I want to talk about the mantle cell lymphoma CMS coverage decision in Q1. Can you talk about mantle cell in terms of its biology? I know it's a little bit more aggressive, so you're probably finding physicians that could be ordering more than four tests. And then I actually want to switch to give Kyle a question in terms of ASPs right after, but I'll stick with that.
Yeah, of course. Yeah. So the mantle cell recurrence monitoring coverage that we secured earlier this year was a really important milestone, both because it significantly increased the total number of tests that can be covered for a mantle cell lymphoma patient in their lifetime. It nearly doubled the potential average lifetime value of a patient in that indication. But also because it was sort of a flagship for us, we created a model for how we can do recurrence monitoring coverage and work with MolDX to be able to expand that to other indications, which we do intend to do over time. The MCL recurrence monitoring coverage allows us to get coverage for tests post-treatment every six months for up to five years and then annually thereafter. That's on top of our original Medicare coverage episode, which allows for four tests per patient during treatment.
So we're now talking about a situation where conceivably a physician could test an MCL patient during induction to assess initial response, at the end of induction to inform transplant decisions, for example. And there's some really strong data to support the ability to avoid transplant if you're MRD negative at the end of induction for MCL, to inform additional consolidation strategies, to decide on the maintenance regimen and the length or duration of the maintenance. And then once the patient has completed maintenance, to monitor them on an annual, biannual basis for potentially many years because mantle cell lymphoma patients can often achieve long remissions, but they always relapse. And so these are patients who are in some cases monitored for quite a long time, and the imaging that needs to be done in the absence of clonoSEQ is toxic in addition to costly for the system.
So it's been a great way. We're not yet seeing, we're early days with mantle cell, right? It's just been a little over a year that it's been in the market. And so right now, the average number of tests we run for actively tested patients is about five tests, but I expect to see that continue to increase as we just lengthen the history of patient monitoring.
Got it. Well, you know, and this leads us to kind of the way to think about reimbursement. You had a couple of different drivers. You had, of course, like the update from $1,717 per test to $2,000. So where are we at in terms of the conversion of private payers to help kind of drive that ASP? Can you talk about your focus on contracting and contracting at a reasonable rate? And then kind of a little bit more of the longer-term excitement. You have the bundled pricing for four tests, but Mantle cell lymphoma might provide kind of an opportunity to think about the longer-term utility of having more than four tests in other indications. So I think that one could be more for Kyle, but you're welcome to jump in too as well.
Sure. I mean, starting with the move from $1,717- $2,007, you know what that did is provided a catalyst for us to go back to the private payers for which we were previously contracted with and start renegotiation efforts to move that rate upwards. We've been successful in that. There are a couple of larger standouts that we still need to close, and we expect to do so over the course of 2026. The other piece is it enabled us going back to payers who had previously weren't contracted with us to establish a contract position. A notable one was Anthem and Centene Florida, a handful of Blue Cross plans that are pretty critical, which we were able to convert during the year. So we're making a ton of progress on what I'll call renegotiation or establishment of contracts with the two outstanding that we do need to renegotiate.
The other piece which we're seeing is momentum in coverage policies. CLL, for example, we had a large contracting win in Q3 or coverage win on the heels of some guidelines updates that provides us some tailwinds there. DLBCL, we had our first large payer initiate a positive coverage opinion on DLBCL. Going to the MCL front and what that means for the longer term, getting paid outside of the bundle of four tests. I think it provides a pathway for us. I think CLL is probably the next logical area where we would focus on establishing a data position to go back and look at some similar type of model, but it provides a clear pathway for us to enable paid-for testing outside of the initial bundle. One other point on the contracting front, generally, those are not restrictive to a bundle approach.
So most of those are open from that perspective.
Got it. Well, I actually was going to ask about great segment, because I was going to ask about CLL. It's not as big of an indication for you relative to multiple myeloma, but you did have the update. How are you thinking about driving penetration in CLL, and can CLL be a pretty big important growth driver for you? Probably more specific than there.
Yeah, you know we don't talk about CLL as much, but it's actually 10% of our business today. And I think that it's an area where the treatment landscape and the way it's evolving is particularly conducive to increased MRD testing over time. So it is an area that we continue to focus on. The guidelines updates, just to refresh, recently incorporated the concept of MRD-guided regimens and suggested specific testing frequency of every three to six months during active treatment for patients who would go on to those regimens. It also incorporated a consideration statement for obtaining a baseline clonality assessment, which, as you know, is needed to be able to perform the ongoing MRD testing by clonoSEQ.
So all of those changes have been really important for us to leverage in our promotional approach, particularly in the community setting where guidelines are influential and where blood-based testing is really appealing. CLL can be tested in the blood or bone marrow, and they're roughly concordant. So it's really an attractive one to do all of your testing in blood. And we've had some really nice data sets that have supported the concept of MRD-guided treatment. Most recently, the Venetostop study was presented this summer at EHA, and we'll see several follow-ups on that data set coming at ASH this year, which will continue to underscore the potential of these MRD-guided regimens, which means the duration of therapy is actually determined by whether or not the patient has reached MRD negativity or not.
So patients have the potential to get less therapy if they achieve that gold standard result of MRD negativity. So we already are increasing our promotional efforts around the guidelines. And as those data sets continue to develop and as FDA approves some of these MRD-guided regimens, because importantly, the guidelines often precede the FDA in this space, we'll be able to leverage that. And I think it'll take some time for the community to adopt these new regimens, but there's clearly a great deal of interest, and this is a central topic in CLL right now.
Yeah, thank you. I just got an email that the webcast is out. Hopefully, I don't even know who to ask about that, but people are listening to you. Okay. I want to stick with NCCN guidelines. Can you run through the mechanics of finding the baseline in multiple myeloma and how important that is for new patient starts?
Sure. So earlier this summer, the NCCN updated their guidelines to strengthen the recommendation for obtaining a baseline clonotype identification for patients with multiple myeloma. And really what that means is getting the sample at the time of diagnosis that has high disease load that can be used by Adaptive to identify dominant sequences that are representative of the cancer cells and that then can be tracked over time. It's a necessity for all of our indications to obtain that baseline clonotype ID, as we call it. And it's sort of a unique characteristic of our test. It's important to understand. Essentially, all of the diseases that we test, lymphoid cancers, are highly clonal in nature, which means that the B cell or T cell population that's affected by the cancer is highly skewed in a patient with cancer.
So if you were to just run sort of a frequency plot of all the B cell clones in a patient with multiple myeloma, you'd see the cancer clones sticking out like a skyscraper in a small town. And that's how we identify the sequences. It's a very direct measure of disease. Those sequences represent the cancer. They're directly located on the cancer cell. And once we identify them, we tag them, and then we can track them. And it's a very precise, patient-specific way of monitoring and quantifying disease. So this is a really important opportunity.
When the guidelines support doing this upfront, it not only means, hey, we're able to drive awareness of the importance of this step in the process and the importance of MRD testing by NGS more generally, but it also encourages physicians to do this step at the time of diagnosis, which has benefits both for Adaptive and for the patient. If we do it at the time of diagnosis with a fresh sample, we have a very high success rate, and it's a very easy logistical process. If we wait until later, we can go back and get an archived specimen from the time of diagnosis, but that takes more time, more resources on Adaptive's part. It can impact the turnaround time if you're ordering an MRD in parallel and waiting on that to be done.
So for all those reasons, we love the idea of getting more and more physicians to do ID upfront, and that's something that we're focused on.
Gotcha. Well, I mean, I would argue NGS clonality is the best approach for immune system-mediated cancers. So why have so few other companies tried this or are doing this approach? And maybe if you can talk about competition specifically using this approach?
Sure, yeah. So I mean, we're fortunate to have, I think, a really strong intellectual property position here that protects the platform in this particular approach. The clonality assessment itself is not a particularly proprietary aspect. There are many ways of doing clonality assessment, and that's not the secret sauce. It's how we apply the findings of the clonality assessment to the identification and quantification of MRD that really, I think, is the competitive advantage. This approach is very specific to lymphoid cancers, so it doesn't really apply in solid tumor. But as I mentioned before, it's a very, very direct way of measuring disease. So if you look at most of the players in the MRD landscape, most of them are doing something where they're looking for indirect measures of the cancer. They're identifying a variety of mutations, let's say, that may be associated with cancer cells.
And if you put them all together, you get a reasonably good predictive value that you're assessing cancer. But we are leveraging biology that's unique to lymphoid cancers. We're looking at VDJ rearrangements within the CDR3 region of a B cell or T cell receptor. And those CDR3s are the complementarity determining regions, which actually confer antigen specificity to each cell. So they're really unique. Each B cell and its progeny have a specific sequence that's specific just to that B cell. And that's why this works so exquisitely well in these cancers that have VDJ rearrangements, these unique sequence rearrangements. So it's unique to lymphoid cancers, and we have the IP to support this approach. And so we've been able to leverage it. And I also should mention that it's patient-specific, but the assay is universal.
We're not recreating individual primer sets every time we get a new patient. We're utilizing the same reagents. It's an algorithmic approach to kind of store those patient-specific sequences and track them over time.
I guess this question could be for both Kyle and Susan. What are the two or three most significant catalysts you think investors should pay attention to over the next 12- 24 months?
I think blood-based testing is going to continue to be a really important one, and with it, the growth in the community setting. So I'm not saying anything new, but I do think that those two focus areas will continue to be very strategically important for us going forward. Ongoing data generation and with it, improvements in guidelines. I expect you'll see new updates to the guidelines that will continue to be supportive in the coming year. And let's not forget that we're still continuing to enhance our margins. And that's an important part of the story that we don't talk as much about today, but that will continue to strengthen our financial profile.
I'd echo Susan's comments on data generation, continued utility of the assay, or more therapies coming on the market that reference MRD. Those are the things that will drive this, and the EMR story is in place. It's more of an execution story right now, but I think the more clinical utility we develop, the more emphasis around MRD, the more clonoSEQ will become relevant.
Yeah, at this point, I mean, I believe almost every clinical trial in multiple myeloma probably has clonoSEQ as a primary or secondary endpoint at this point. Are there any really large drugs that have a potential to--I'm not asking clonoSEQ specifically, but any big multiple myeloma clinical trials coming out?
You know there was just a pretty important one that was out this summer, just for everyone's awareness. MIDAS was a study that looked at the ability to avoid a transplant in patients who are MRD negative at end of induction. That was a study that was large, 800 patients, randomized controls. The first time that this was shown in a well-designed study of that size, that you can, in fact, safely avoid transplant in these patients. That type of study, there are a number of additional ones that are going on. There's a really important one called SWOG 1803 that won't read out probably until 2030- 2032 to get all of the data. It's been going on for years, and this is sort of viewed as the gold standard for MRD-guided therapy in the future.
And we should see some initial readouts from that in the next couple of years. So everyone's very excited about that stuff.
Thank you so much. Really appreciate you having me here.
Thanks, David.
Thank you, David.
Great answer by.