Great. Good afternoon, everyone. Thank you so much for joining us. We're really pleased to have with us Susan Bobulsky, the Chief Commercial Officer of MRD over at Adaptive. To start, Susan, could you provide a snapshot of Adaptive's MRD business as it stands today?
Sure. Thanks so much for having me today, Salveen. So as you may know, the MRD business is comprised of two pillars; our clinical business, where we sell to physicians, and our pharma business, where we enable drug development. And in the clinical business, clonoSEQ is really well established as a gold standard for MRD testing in blood cancers. And on the pharma side of the business, it's also the test of choice for drug development in these particular malignancies. So let's talk a little bit about where we are with each of those businesses today. First of all, I think we've established a number of key moats that have uniquely positioned us within our marketplace. First of all, on the technical side, the sensitivity of this assay is bar none.
We have established a robust IP position, and we've published more than 160 studies demonstrating the clinical validity and utility of the assay in various disease states. We're also the first and only FDA-cleared assay for MRD detection, and we're really broadly covered with more than 300 million lives in the United States. So, today, our 2024 revenue guidance is $135 million-$140 million. We anticipate about 65% of that to come from the clinical business and 35% from pharma. We have significant room to continue to penetrate both of those markets. We are, on average, around 8% penetrated in the clinical business and around 20% in the pharma business.
Varies by indication, with myeloma being our most heavily penetrated disease state in pharma, and ALL being the most heavily penetrated in the clinical side. So we have a lot of room for growth, and at this point, a lot of our opportunity is really around execution. We are laser-focused on growing our volume, growing our ASP, and reducing our costs for profitability in the relatively near term. And we have the right team in place to grow the business, to achieve the efficiencies that we've outlined, and so we feel that we're in a really strong position to continue to solidify our leadership.
Great, and I believe the company recently completed a strategic review, which determined Adaptive would keep the MRD and IM businesses internally. Can you walk us through how this decision was made?
Sure. So on the MRD side of the business, I think we have a pretty concrete sense of what we have in hand, and we did entertain offers from a number of potential strategic buyers. Ultimately determined that those offers undervalued what we believe to be the future potential of the clonoSEQ business. And so we decided that given that we have the cash, we have the strategy, we have the people, that we should continue to execute and strengthen the financial profile of the business to further increase the value over time. On the IM side of the business, you know, we're encouraged by the progress we've made and the potential we see there, but we recognize that it's still early, and we have to continue to validate and demonstrate some of the proof points that we've outlined.
Wanting to preserve the optionality for that business over time, we decided that we would make some targeted investments in the near term and see if we can, in fact, generate those proof points that, that we think will be valuable to the, to the outside world. So in summary, we have the cash we need to bridge to profitability for MRD to deliver on some of those targeted investments, in the near term for IM. And so we will continue to do both under the same umbrella, albeit with segmented P&Ls and aligned resources to each of the individual businesses, which will increase transparency externally. And we still believe in this fundamental thesis that these two businesses could generate greater value separately, but at this point, it's a matter of optimizing the timing.
Hmm. What are the areas of the MRD business where Adaptive is investing most heavily? So when you did that breakout of how your businesses lie between pharma and clinical, but then also the penetration, where do you see the most growth, and can the proportion of the business shift, you know, further to one side versus another?
Yeah. So, I mean, first of all, when you say heavily investing, I think what I tend to think is that rather than right now heavily investing in net new things, we are focusing on leveraging the investments that we've made in the recent past, to continue to drive growth, both sides of the business, as well as to generate efficiencies across the P&L. So a couple of places where we are investing moderately are, one, to increase lab efficiencies, particularly with the transition of our sequencing to the NextSeq X Plus, NovaSeq X Plus, excuse me. Secondly, to continue to generate data in key areas where we can build both on the clinical and pharma sides, we can build our penetration on Hodgkin's lymphoma is a great example. And then thirdly, to grow our ASPs, and that does require some investment.
We've expanded our market access team, expanded some of the partnerships and processes that we can leverage to further optimize revenue cycle management. I think those are a couple of areas I would point to in particular.
What do you think about the Adaptive story and the platform, or what about the Adaptive story and platform do you think that investors are missing?
I think typically investors understand the clonoSEQ assay, the power of that assay, and the MRD business in general. I think the immune medicine business tends to be less well understood, and I get it: it's a bit of a black box for investors. I do think that, you know, based on what we've discussed with the strategic review, we've recognized that we need to further advance and validate some of the developments in that part of the business, and in doing so, we can increase the understanding that will help investors better value that business. You know, we have, I hope, by segmenting the P&Ls, created this greater visibility to how we are investing and what the cash burn looks like on each respective side, which I think will further support understanding.
And then I do want to highlight our healthy cash position, which I think is not always fully appreciated. That, combined with the achievements we've been able to make over the last several years in reducing, those will be things we'll continue to do in the coming year and years to come, which I believe are the things investors need to understand.
With clonoSEQ, in some presentations at ASCO assessing the clinical. Can you remind us what was presented and just the clinical importance of this data?
Sure. There were quite a few exciting presentations, a number of orals at ASCO and also at EHA, that demonstrate both continued prognostic value as well as the clinical utility of the assay. So a couple examples: in pediatric ALL, the Children's Oncology Group published or presented the largest to-date study comparing blood and bone marrow-based assessment of MRD by clonoSEQ, showed a strong concordance between the two sample types, and I think really further supported the case for leveraging a less invasive MRD test modality, again, with clonoSEQ, to monitor these children with this really challenging disease. The second one I would highlight is the MRD2 STOP study, which was done by University of Chicago investigators, and is an example of clinical actionability of leveraging the deep sensitivity at 10^-6 .
They were able to show we discontinued from maintenance therapy and could sustain MRD negativity while off therapy. Another myeloma study, the PERSEUS study, was a look at daratumumab added to VRd in the upfront newly diagnosed myeloma transplant-eligible setting, showed that at 10^5 and 10^6 sensitivity thresholds, dara increased MRD negativity rates, and then subsequently, that did translate to PFS improvements. Those studies both really highlight the importance of deep sensitivity with the effectiveness of the drugs we have today in multiple myeloma. The PERSEUS study is designed with an MRD-guided discontinuation or de-escalation component, which the data is still in development, but we are eagerly awaiting to see how we can use MRD to guide dara in the maintenance setting as well.
On the back of the FDA Adcom vote to support MRD as a primary endpoint for accelerated approval here in multiple myeloma, just speak to the opportunities this opens up for you in terms of conversations with partners, and just maybe broadly frame the anticipated impact here.
Sure. We are very pleased to see the unanimous vote by the ODAC committee. I think this is a tremendous milestone for multiple myeloma patients, something that the community has long been waiting for. We do anticipate that there is some positive upside for, should they choose to accept the recommendation. First of all, on the revenue recognition front, I think we can accelerate the realization of revenue from existing studies and potentially generate new bookings, as some companies will choose to reprioritize myeloma assets, given the faster path to commercialization that's available. On the milestone front, I think we'll accelerate the realization of certain milestones where we already have MRD incorporated as an endpoint, and we'll likely see, and we already are seeing, version of some studies from secondary endpoint status to primary endpoint status.
Those things, combined with the positive halo effect that I anticipate in the clinic, we're having a lot of conversations with physicians and patients about what this unanimous vote means for just the credibility of MRD as a measure of response and a predictor of outcomes, and how it can be useful in patient dialogue. So I think that will be meaningfully clinically over time as well. The conversations we're having with partners, every company is talking about this. We've already had several new studies based on reprioritized myeloma assets. We've had several new primary endpoint studies, and several studies convert from secondary to primary just since April 12th. So I anticipate that that trend will continue, and companies will leverage this to the fullest extent possible, not only in myeloma, but in CLL and other disease states, where people are already...
These pharma companies are already starting to anticipate how they can leverage MRD in their development programs.
Perhaps you can talk about that as the real-world support for the utility of clonoSEQ continues to emerge. What efforts, I guess, is Adaptive making to increase penetration across the multiple approved indications? So you're talking about CLL from one side, but how are you doing it from this other side of the business?
Yeah. On the clinical side of the business, there are four major things that we're focused on to increase penetration, and one of them is related to clinical actionability. The others are increased testing in blood, expand to new indications, and grow our use through EMR integration. So really briefly on each of those, clonoSEQ in blood, almost 40% of MRD tests with clonoSEQ today are done in blood. We expect that number to grow above 50% in the not-too-distant future, based both on expansion of use in primarily blood-driven indications like DLBCL and CLL, as well as complementary use of blood-based testing in traditionally bone marrow-driven indications like ALL and myeloma.
We've developed important data in both of those indications, most recently, the COG data I mentioned in ALL, and the ASH data from Ben Derman at, in myeloma, to support continued adoption. That's going to be key not only to increasing the frequency of testing over time, but also to penetrating in the community where bone marrow draws are less commonly done. Second area, expanding indications. Mostly our focus there is in non-Hodgkin's lymphoma, mantle cell lymphoma, and cutaneous T-cell lymphoma are two subtypes that we hope to launch commercially in the coming year, and we are imminently awaiting a final word from Medicare on the coverage determination for mantle cell, and we expect to submit for CTCL later this year.
On the actionability front, in addition to that MRD to stop study I talked about at ASCO, some really exciting data coming out over the next year. You know, in 2025, we expect two very practice-changing studies. One is called EndRAD. It will potentially allow pediatric oncologists to eliminate the use of total body irradiation in conditioning pediatric patients for transplant. It's a huge impact for these patients to their quality of life if they're MRD negative. And the other study is called the VENETOSTOP in CLL, and it would allow MRD-guided customization of duration of therapy in the frontline setting. And these two studies, we anticipate at least some readouts in 2025. So it's a big area of opportunity for MRD as a concept.
Lastly, EMR integration is going to increase stickiness for our existing customers, and it's going to make it easier to adapt the product for new customers, so we're working quite hard on that.
On the Q1 EPS, I think you noted that the published preliminary Medicare gap fill rate was about $1,823 per test. Can you frame the implications of this to Adaptive and how Adaptive's discussing this published preliminary rate with commercial payers?
Sure. So we are pleased to see that rate. It is actually an increase over the implied per test rate, that is, conveyed as part of our Medicare episode-based payment. And we anticipate the final rate will be in, put into motion and will be active as of January 1st. And in the meantime, we will continue negotiations with MolDX on the final. But we based on this preliminary rate, we believe that there may be some potential upside to our ASP models, and at least it certainly solidifies our confidence in delivering on the ASP, increases that we've projected and that we've discussed publicly. For commercial payers, this published preliminary rate is really key.
There are a couple of large payers, Anthem being an example, that are holdouts on contracting with us on clonoSEQ, and they've specifically said they're waiting for this number. So now that it's been published, we can go forward, reengage, and hopefully bring the contracting process, process to completion. Over time, we may also be able to use that rate to renegotiate existing contracts favorably.
Can you speak to the EMR integration efforts? How has the integration been progressing, and when could this meaningfully impact the top line?
Sure. It's been progressing well. We did our first four sites, beta type sites, smaller sites intentionally, towards the end of 2023. And we've seen positive traction with all four of those sites. Actually saw the business as a whole across those four sites increase by 40% within a quarter of integration, which I think was a nice impact. Also saw a significant increase in the number of ordering providers at those sites, which speaks to the ease of the use of an integrated test. We have since integrated two more sites, much larger sites, and we were able to do so in half the time of what we did with the beta sites. So we're really hitting our stride in terms of efficiency of making this happen at each individual account.
We have 12 more sites in active work with their IT departments and ours collaborating, and we anticipate by the end of the year to have 20-25 sites live, which would likely represent, based on the sites we are projecting, 15%-20% of our business. So, you know, we do anticipate that you'll see more impact on our volumes in 2025, and even more so in 2026, when not only will we have completed a larger number of Epic integrations, but we'll also be live with Flatiron's OncoEMR system, which is the largest community oncology EMR system in the country.
Can you walk through the profitability targets for the MRD division?
Sure. So we have thought about profitability in sort of two standard ways. First, we've projected that we can be EBITDA positive by the end of 2025, and that we can be cash flow breakeven by the first half of 2026. And based on what I've talked about, the volume trajectory, the ASP growth, and the reductions in costs that we've projected, we're confident that we can achieve those targets within those timeframes.
You've also guided as a company towards 2024 revenue guide of, of $55 million-$140 million. Can you help us understand what's baked into that guidance?
Yeah, absolutely. Anticipate about 65% of that coming from the clinical business, about 35 from pharma, as I mentioned earlier. Within the clinical business, we're projecting 40%-45% year-over-year revenue growth, and that will come from both volume and ASP improvements. And so on the volume side, I think the consensus has been around 35%, which I think is fair, and the ASP growth, we've stated in the past, we expect $200 increase in ASP over the course of 2024 and 2025. And so you could say about $100 this year. And again, on track to, to deliver on those, those trajectories. On the pharma side of the business, some positive tailwinds that we're experiencing with the ODAC vote.
We also are continuing to closely monitor some of the headwinds we saw last year, just in terms of budgeting constraints from the pharma businesses. But overall, you know, we think 10% year-over-year growth is very much reasonable. And so I think that's a good overall-
If there's one thing contributing to upside or downside risk to this guidance, what would it be?
I would say that, you know, there is variability in all of these parts of the business, but probably the primary place where we have some greater degree of uncertainty is in pharma, where, you know, some things are simply just not in our control: the timing of studies, the pace of enrollment. And particularly when you think about upside, pharma milestones, I think, would be the main area I would highlight.
Can you speak to the competitive dynamics here with other players who are working on similar efforts, and how to think about that in the context of growth?
Sure, yeah. So, I mean, we are well-positioned here as really the only option for both clinical testing and the only FDA-cleared test. So on the pharma side, the FDA refers our customers to us if they don't find us themselves, and we're very fortunate to be in the position to have developed credibility as a development partner with every company that's really operating in this space. We do occasionally encounter competition. The only space right now where we actively see any competition is in DLBCL, which is a circulating tumor DNA assay. And so there are other companies who are exploring those technologies, but I still feel we're very strongly positioned. And in the clinic, we encounter more traditional technologies to some extent as competitors, so cytometry, in particular.
But we've conducted many head-to-head studies and demonstrated time and again, not only the improvements in sensitivity, but also specificity that we can offer. And so, I think we're well-positioned to compete in those settings, and sometimes it's just a question of time it takes to move someone to trying something new.
Maybe speak to the growth levers here, like your biggest growth levers going forward. So you've talked about where things could play out with MRD in as a diagnostic or use in clinical trials, but where else do you think there could be growth?
Well, you know, I think a growth driver for us from a revenue perspective is going to be in ASP, and there are a number of things that we're investing in to try to help you know, accelerate and solidify those increases. So we have, for example, worked hard to expand our coverage. I talked a little bit about that earlier. We are actively working to grow our business disproportionately in our covered indications relative to less well-covered indications, doing that through both ordering policy shifts, through field force incentive programs. We are also expanding contracting. We have about two-thirds of our business contracted today and expect to be able to meaningfully increase that over the coming year and a half.
And then, operational improvements that will increase the likelihood that we actually get paid at the rate that we should be getting paid. So those are some areas where revenue growth will come from on the clinical business. On the pharma business, other growth drivers, besides myeloma, which we talked about, are CLL, where increasingly MRD is being considered as an important endpoint, and perhaps in the future will be, have the option to become primary as well. And non-Hodgkin's lymphoma, we had been primarily focused on DLBCL over the last year or so, but now are seeing the opportunity to expand significantly in mantle cell lymphoma and in follicular lymphoma as well.
Overall, how do you think the MRD testing landscape will develop over the next two to five years?
You know, we've come a long way. We, I think as pioneers in this space, we had the opportunity to see, you know, the conversation shifting from what is MRD, to why should I use MRD, to now, how should I use MRD? And so that's really where the focus is going to be over the next several years, is demonstrating the use cases for how MRD can direct or inform a decision, to increase therapy, to start therapy, to deescalate therapy, to discontinue therapy across all of these indications. That's where the energy and excitement is, and I think that extends to solid tumor as well. It will be interesting to see in the solid tumor landscape how the more crowded, you know, set of competitors, how they all differentiate one another.
But in heme, I think it's clonoSEQ's opportunity to demonstrate how it can be applied clinically.
With regard to the company and capital allocation, I guess, how is capital being allocated between this part of the business and IM at this point?
Yeah. So, you know, in general, the allocations that we think about for our P&L when we're splitting resources, let's say, are 75, 25. And certainly we have defined investment targets for both businesses, and in particular for the immune medicine business. We've created some, you know, gates so that we can evaluate our progress and then determine whether to pursue the next tranche.
Can you speak at all to the IM business and when we might start to understand kind of the value aspect of that division?
I'll just say that we're working very hard, and we're very encouraged by some of the early things that we've seen internally, so I hope to give you an update soon.
With that, let me open up to the audience for any questions.
Yes. Sarah, what do you... or Susan, what do you think is, you know, when you think about the business long term, where would you want to see this evolve to over time?
I think there's an opportunity for the clonoSEQ assay to be incorporated in a very wide range of the continuum of disease monitoring, not just one particular time point, but when combining blood and bone marrow-based testing, combining cellular and ctDNA-based testing, looking at early precursors of disease, as well as sort of the full-blown versions of disease that we're talking about today. We have the opportunity to really expand. The technology platform has tremendous advantages, and it has really only, I think, scratched the surface in terms of the breadth of things that it could be done with it. So I'd like to see us be able to see clonoSEQ embedded throughout the entire continuum of care, from sort of the time when a patient has a precursor condition, you know, to end-of-life care.
Have you disclosed the number of partners you have at this-
We-
with regard to, you know, pharma and with regard to pharma companies?
We haven't disclosed a specific number, but I mean, suffice it to say that we, we partner with any major company that you're familiar with in this space. We certainly have over 40 partners.
With that, Susan, thank you so much. Really appreciate the discussion today.
Thank you. I appreciate it.