Okay, we'll go ahead and get started. Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name's Anupam Rama, one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Priyanka Grover, Rathi Pingali, and Joyce Zhou. Our next presenting company is Syndax, and presenting on behalf of the company, we have CEO Michael Metzger. Michael.
Thank you, Anupam. Nice to see everybody. Thanks for joining us. Thank you to JPMorgan for the invitation to present today. It's a pleasure to be here. Pleasure to see all of you. Let's get started. So, a reminder, today I'm going to be making some forward-looking statements, and we'll jump right in here. So, 2025 was a transformational year for the company. We've transitioned successfully to a commercial-stage oncology company with the launch of Revuforj and Niktimvo, two first and best-in-class medicines with great promise for patients. And we've really proven that we've been able to deliver for patients: three FDA approvals in the span of about 14 months, and a very strong launch for two drugs. Really, our bed to bedside, sorry, bench to bedside, in about four years, which is sort of unprecedented speed, really shows the depth and commitment of our team to generate fantastic products.
We're here. We've generated really strong results, and we'll talk about that today. We have a lot of momentum going into 2026. We're on the road to profitability with growing revenue and stable expenses. We have about $400 million on the balance sheet to really execute on all of our goals. We have two products in front of us that are not only approved, but we have very large market opportunities and differentiated product profiles in order to execute long-term and the commitment to maximize value. Let's start with Revuforj. Revuforj is the first and only menin inhibitor to be approved in multiple acute leukemia subtypes. It was first approved by the FDA in 2024, in November, for relapsed refractory acute leukemia with a KMT2A translocation. A second indication, most recently, in November of 2025, for relapsed refractory NPM1 mutation.
I'll remind you, this is a disease of acute leukemia. These are perhaps some of the worst prognoses that you can have as a patient. So, there's a very high unmet need and urgency to treat. And this is the market backdrop. So, current Revuforj indications unlock perhaps a $2 billion total addressable market in the relapsed refractory acute leukemia setting: 6,500 patients between the two subtypes. And as you approach the front line, you get to about 9,000 patients. So, an even bigger opportunity, really unlocking about a $5 billion total addressable market. And we have a comprehensive clinical development program underway to unlock this total opportunity. And what's unusual about menin inhibition, and specifically Revuforj, is we're addressing about 50% of the acute leukemia AML market with a targeted therapy. I'll say that again, a targeted therapy, so we can select the patients that we can treat.
These patients, through the use of transplantation, we can drive very high rates of response, drive patients to transplant, and then put them back on for maintenance treatment. That elongates the time on therapy, keeping patients in remission for months, if not years. That extends the size of this market and changes it from a, what you'd call, a niche AML market to a very, very significant one, as $5 billion plus suggests. We talk about Revuforj in terms of being really well-positioned for success with a best-in-class profile and first-mover advantage. Best-in-class profile. We have unmatched efficacy with our drug compared to other competitors in the class. This is an efficacy-driven market. That means that physicians are first and foremost concerned with getting their patients to a response, a deep and durable response. Our drug allows that to be accomplished most often.
It's been approved in multiple subtypes, as I mentioned. So, AML, ALL, adult, pediatrics, we cover all the subtypes. It also allows for patients to be dosed individually. So, we have different dosage forms that allow different amounts that can be dialed in by the physician. And the drug is extremely well-tolerated. And it can be used concomitantly with other medicines. So, physicians are not only using this as a monotherapy where it's approved, but they're also thinking about how to use it in combination. And our drug has shown itself to be well-tolerated and effective with other drugs. And also, in the scheme of what other drugs patients are receiving, such as gastric acid-reducing agents, our drug does not have an effect on those agents. So, it's a best-in-class profile, highest efficacy, really well-tolerated, and really is dialed in for the patient. And physicians have recognized that.
And we have first-mover advantage. So, we were the first to be approved menin inhibitor. And so, we have now a year-plus on the market with a robust and growing prescriber base. It means a lot to be in front of physicians and working with them for a year. They become very comfortable with your drug. They prescribe it to their patients. And if they have good results, they tend to come back and prescribe it again. And that's, in fact, exactly what we're seeing with Revuforj in its first year. So, we've built a competitive immunity and really an excellent, excellent, trusted relationship with physicians. We have really excellent market access. So, we've been able to bring the drug to patient bedside in four days or less. That's industry best. And our reimbursement from payers is at a very high rate.
It sits at about 97%, 98% for payers in KMT2A. And it's building exceptionally fast in a new indication for NPM1 as well. So, we are making excellent progress, not only to get the drug to patients, but actually get it paid for in its first few months on the market. And as I said, we are a trusted partner at HCPs. We put the patient first. We do everything we can in order to bring the drug to patients. And physicians recognize that. And so, when they're looking for something for their patients to treat them effectively and quickly, they come to us and we deliver. All right, so let's talk a little bit about our performance. I'm privileged to be able to pre-announce our results as of today for the quarter and for the full year for Revuforj.
The strong launch really underscores the exceptional product profile we have and really the wonderful execution of this team. So, in the fourth quarter of this year, $44 million in preliminary net revenue. That's up 38% from the last quarter. I put it a little bit in perspective. The last quarter grew at about 25%. We're now growing at 38%. So, tremendous growth from a revenue perspective, which you would expect with a new indication and the dynamics around KMT2A. We've really built on, and I'll also mention that the sales are really driven by demand. So, demand is where you'd like to see growth. And we have that with the launch of this new indication, as well as what we're seeing with KMT2A. Inventory is stable, two to three weeks. And that's what we've guided to historically. It remains the same for this quarter.
We've really built on what we've done. We have a lot of momentum. And we've built on what we've done with KMT2A. The launch of NPM1 is off to a fantastic start. And I would say it's driven also by the fact that physicians have great knowledge of the product. They've been using it for a year. Some of that use has been in NPM1, not on label, but it has built their confidence and understanding of how to utilize the drug. And they're very well aware. And we're welcoming when we sat with them at ASH this year and showed them the data. They were excited about the label, excited about bringing this to their patients. So, that builds a lot of momentum as we go into the fourth quarter. And you can see it here.
It really accrues in the TRx where we've had 35% quarter-over-quarter growth from last quarter, and for the full year, $125 million in full-year revenue, and if you put that in perspective, this really surpasses all the benchmarks that we've seen for other AML therapies in the category, and it's not even really close, so we expect this to be a continued acceleration in demand and growth throughout 2026, and we have the team to execute on that, so let's talk about some of the evolving clinical practice patterns that we see that we believe will help to grow the brand into 2026 and beyond, so first of all, there are really three things. First, I'll mention movement to earlier lines of therapy. Patients are being treated, and physicians have said this from the beginning. They're treating them in the second line and third line primarily.
The majority of our patients are being treated earlier. Why is that important? It's important because if you treat them earlier, they tend to have a higher rate of response. They do better. They stay on drug longer, have an opportunity even to be transplanted. It really drives the earlier treatment. It drives the utility of the drug. We've also seen physicians give the drug in combination. It's a growing phenomenon. That's what they told us they wanted to do. As you move towards the front line, those are combinations with drugs like Venetoclax, as well as chemotherapy. We're starting to see that use built. This all accrues to longer duration of therapy. Second key point, we're building this transplant rate in KMT2A. Historically, KMT2A patients in the third line have about a 5% chance of being transplanted.
In our clinical trial, we were about 25% transplanted. We're now at about a third transplanted. We expect that number could go to 50% or higher. That would be an incredible result for these patients who have perhaps the worst prognosis in AML. What that is usually followed by is post-transplant maintenance. Physicians told us from the beginning that they wanted to put them on long-term maintenance, a year to two-year of maintenance. And that is precisely what we're seeing. In the last quarter, we were able to see about 35%-40% of patients going on post-transplant maintenance. Again, that drives the duration of therapy and really is good for patients. And then third is this new indication. We've tripled the patient population by getting NPM1 approved. So, we have really growing adoption. We see it in the TRx, growing adoption in NPM1.
We have best-in-class profile in NPM1, as well as KMT2A. That will help us drive the brand. These are three phenomena that we think are very important to the growth of brand in 2026 and beyond. Let's talk about the future. We've been first in a lot of things in the menin space. We were the first to clinically validate the menin inhibition. We were the first to get an FDA approval for a menin inhibitor with Revuforj in KMT2A. We were the first to receive an FDA approval in NPM1, relapsed refractory AML. We've done a lot of things first. We have a lot of momentum. We have a fantastic plan, and I'll tell you a little bit about that in a second. We have a great clinical development plan to drive utilization and get approval in the front line.
We have tremendous momentum to get there. Let me tell you a little bit about our plans. We're advancing the broadest data generation plan to rapidly deliver practice-changing Revuforj evidence and support global registrations. There's a lot of trials on here. I'll just hit some of the highlights on subsequent slides. It's really a plan to generate a robust and differentiated body of evidence supporting Revuforj. Let me start first with the relapsed refractory piece of the business. We had AUGMENT-101. You're familiar with it because it yielded two approvals for both KMT2A and NPM1. That trial continues to pay dividends as we continue to look at that data. We also have combo trials that are coming through with practice-informing data. We presented 13 abstracts at ASH this year, one being the SAVE trial, which is a newly diagnosed patient.
We've also had data in relapsed refractory setting in combination. So, these types of data will be really, really important to enable the physicians to choose what kind of combination and which kind of patients they want to treat their patients with. Next is the maintenance and MRD relapse setting. We have a robust data generation plan underway in collaboration with some of the leading academics and cancer centers in the country and around the world to really look at maintenance and look at MRD relapse as important uses of the drug in the future. And then lastly, I'll talk about front line. A lot of focus on front line for us in the coming year. Encouraging data, which we've seen in both the fit and unfit setting in combination.
We highlighted Beat AML and the SAVE data, which I just mentioned, which are both for patients who are fit and unfit for chemotherapy. These are the next big frontiers for us as we unlock the largest opportunity. The EVOLVE and REVEAL trials, these are pivotal trials that are underway as of this year, 2025, last year, 2025. In 2026, we'll accelerate that. And importantly, they have endpoints to support potential accelerated approval as well as full approval. And then last, I'll mention the RAVEN trial, which is a highly innovative trial that's planned in fit KMT2A. This is a trial looking at venetoclax plus azacitidine plus our drug in patients who are usually fit for chemotherapy.
The idea here is to be able to give them a less onerous regimen where we could have fantastic results in efficacy, but also spare the toxicity that you often encounter with high-dose chemotherapy. So, a very innovative approach and robust to not only get to front line and be the first to front line, but also to fill in data in the near term over the next few years in these other settings. All right, so let's switch gears and move on to Niktimvo. So, this is our second drug. Niktimvo is poised to deliver on the promise of CSF1R inhibition in chronic GVHD and beyond. It's the first and only CSF1R blocking antibody to be FDA approved in the third line plus GVHD setting. Importantly, as a novel mechanism of action, it affects the macrophage and monocyte.
And it has an important impact on the inflammatory and fibrotic aspects of the disease. So, physicians feel there's an unmet medical need in this category. And we're able to fill it with a new drug that has just excellent promise. The feedback since the launch of this drug has been extremely strong. We've been hearing from physicians that it really fulfills on the need to impact various organs that are impacted from GVHD. And so, this brings to bear all the things that we had hoped for a new agent in this category. Trials are underway in the first line to really unlock the opportunity in chronic GVHD and in other indications, such as IPF, a very large opportunity, which I'll mention in a minute. So, just a look at the market where we are today. 6,500 patients currently treated in third line plus GVHD.
It's about a $2 billion total addressable market for us in that indication. The opportunity is to expand to front line where you really unlock a larger amount of patients. We're talking 15,000-17,000 patients once you get to front line. Worldwide, it could be significantly larger than that. And beyond just GVHD, we have this opportunity in IPF, as I mentioned, larger opportunity, 150,000 patients in the US suffering from idiopathic pulmonary fibrosis and in need of new therapy. So, again, I'll mention the results that we highlighted this morning in our press release. Very strong results for Niktimvo, really underscoring the importance of this novel medicine to patients and certainly to us. Niktimvo generated $56 million in preliminary fourth quarter 2025 net revenue. That's 22% up from the last quarter and $152 million in preliminary full year 2025 net revenue.
The company expects to share its share, which is 50%. We do have a collaboration with Incyte. We book about 50% of the net profit, which equates to about 25% to 30% of Niktimvo net revenue. Niktimvo net sales are annualizing at greater than $200 million. It's not even its first full year of launch. It's about 11 months of launch. So, this also really blows away other benchmarks in the category when you think about another drug, Sanofi's drug, Rezurock, in their first year did about $136 million. And we are already well surpassing that. So, the contribution to Syndax is expected to grow materially as we move beyond what we've done this year and continue to penetrate. And it's a very important drug for the portfolio, as you can see. So, there are multiple drivers to continued Niktimvo growth in 2026.
Rapid adoption into the fourth line, that's primarily where we're penetrating today. And growing utilization in the third line for GVHD. Second, I'd say patients are staying on therapy for a long time. This is not a drug they take for a month or two. This is a drug they could take for years. We've seen it in our clinical trial where patients are staying on for multiple years. And we're seeing it play out that way in commercial as well. So, you have patients from launch. Most of the patients from launch are still on therapy, which is remarkable. So, that will build over time. It has a stacking effect in terms of building the brand. And so, we expect that to continue. And then last, I'll say we have a very solid prescriber base. 90% of the U.S. bone marrow transplant centers are already prescribing.
So, again, very healthy setup for us as we grow the brand into 2026 and beyond. And of course, we have a very robust clinical development plan underway to drive growth. Chronic GVHD, two trials primarily. One is the phase two trial, Axatilimab plus Ruxolitinib, otherwise known as Jakafi. Top line data expected in this trial in the early part of 2027. And then a pivotal trial for Axatilimab plus corticosteroids, top line data expected in early 2028. And then I'll turn our attention to the idiopathic pulmonary fibrosis trial, MaxPhier, the phase two trial, Axatilimab plus standard of care. We are running that trial at the 26-week randomized double-blind placebo-controlled multicenter primary trial with primary endpoint being change in FVC. And the top line data is expected in the second half of 2026. And we're excited about that result.
Really, if that result is a positive result for the brand, it could be transformational. So, let's talk about 2026 priorities and anticipated milestones. So, I would say that we've really accomplished everything that we set out to do in 2025. And that's not easy to say often. So, we feel really, really terrific about what we've been able to accomplish. And we have a lot of momentum going into 2026. So, let me talk about a few of the milestones in 26 as we really are focused on generating value based on focused development and data generation in our pipeline. That's how you get the most out of these two very impressive drugs. So, first, I'll say we're going to report top-line phase 2 Axatilimab data in the second half of 26. Of course, I mentioned that just recently, just a minute ago.
We're advancing our global enrollment in a pivotal first line trial for Revuforj in fit and unfit patients. We're going to advance both of those and be focused there. We're going to continue to publish and present industry-leading clinical data, including Revuforj data in front line and the maintenance setting. We're initiating this RAVEN trial, which is that innovative trial I mentioned for fit KMT2A patients. And we're going to initiate a proof of principle trial in a clinical trial with Revuforj in myelofibrosis, a new area that we've had some data and very exciting data that was recently published at ASH this year. We're going to follow up on that. So, with that, these are our anticipated milestones. We feel like we have a tremendous amount of momentum going into 2026.
I've never been more excited as a leader of a company to have the people at Syndax who are so dedicated and passionate about what we do. We've brought two fantastic medicines to patients, and we've done it in record time, and now it's time to really build the opportunity and build tremendous value for shareholders and patients alike, so with that, I'll turn it over to Anupam for questions. Thank you so much.
Thank you, Michael. I'll ask the first couple of questions, but there's going to be an opportunity for folks in the audience to ask a question as well. So, feel free to do that. I was wondering, Michael, if you could put into context this first year of launch with Revuforj as it compares tracking relative to historical analogs.
Yeah, I mentioned a little bit of it in my talk. Look, this has been a year where we started fast and we ended fast. There really hasn't been any let up. Both brands have surpassed what we've seen with other analogs. In AML, the closest analog did about $80 million. Gilteritinib in its first year, we did $125 million. So, it's not just the sales, though. It's scripts, new patients, it's formulary coverage, it's everything across the board. So, it's execution, it's the drug profile, but it's also execution of this team. So, very proud of that. And likewise for Niktimvo. I mentioned our competitor who's also approved in third line, $136 million in their first year. We did $152 million. Again, addressing more patients, patients are staying on longer. We're really doing something different in a category and hopefully better for patients. But that's what I'm most proud of.
I think it speaks to what we've been able to accomplish with these profiles.
I know you just launched NPM1, but what are you looking to learn in the next, let's call it two to three quarters or year where you might get comfortable in giving some sort of guidance to the street in terms of what we should expect?
Yeah, no, it's a new launch. The way we think about it, at least, it's KMT2A. We have about a year of experience. We have NPM1. It's a bigger patient population, some different dynamics in terms of transplants, in terms of having a competitor. There are other factors. And so, I think we need a little bit of time to sort through how that all kind of comes together. What's clear to us is we have a larger market opportunity. We have a best profile. We are extremely well positioned to execute. And we're going to dominate this space. So, it's not a matter of if, it's a matter of when. And we'll talk a little bit about as we go, probably when we get into the year, give more specific metrics on how we're building share and things like that.
But now it's a little bit early to do it. I think we're, based on the sales that you saw today, first quarter, sorry, fourth quarter of this year, $44 million, up 38% versus last quarter, just speaks to the uptake that we're seeing in NPM1. And truly, what we're seeing with KMT2A is patients come back on therapy in the maintenance capacity.
Maybe just then focusing in on KMT2A, I think on the third quarter, you've been talking last year about getting 50% penetration by the end of the year. Where did you fall relative to that kind of commentary as well as now looking to 2026, how do we think about penetrating the market?
Yeah, we were pretty steadfast that we would get to about 50% penetrated in KMT2A. I'll remind you, there's nothing approved for KMT2A. We're at standard of care also doesn't work very well, so patients are really in need of new therapy. We're able to deliver that. And when you have that kind of dynamic, you have fast uptake. We've been able to penetrate about 50% of the KMT2A market. That's about 2,000 patient incidences. Every year, unfortunately, for patients, you have about another 2,000 that you have to treat. We will continue to penetrate beyond the 50%. We've seen targeted therapies get; some of the best have gotten up to 90% of a targeted market. We think we can accomplish that over time. That's the goal. We want to really penetrate as much as possible.
And there's really nothing in our way to hold us from achieving that. So, that's a continuing story. But we've gotten to where we wanted to get this year. Next year, we'll continue to push.
And then on NPM1, I know it's early.
It is.
Any anecdotal commentary you can have about the NPM1 market, what you're seeing, there is a competitor like you mentioned in the space?
We're seeing the profile is really well received. I mentioned it in my remarks. We went to ASH. We had lots of really impressive meetings with physicians. They're very well aware of what this drug does in KMT2A, and NPM1 is a growing understanding. But a lot of these physicians are already using the drug. They were using it before approval. Now this is a real moment of excitement where they see the full opportunity in front of them. They can present or they can bring this to patients on label. They can combine it with other drugs. We're providing them with data beyond just monotherapy data to support their utilization. So, the enthusiasm is real. And the momentum we see is a result of that. So, those are early days. But when they see best in class profile, they want the highest rate of efficacy.
They want a well-tolerated agent. It covers all the subtypes. We're talking about KMT2A and NPM1. We're specifically asking about NPM1, but adults in pediatrics, that's meaningful to them. They can bring the product, one product to their patients. And so, that's the momentum. That's the coverage. And that's what they tell us when we talk to them about how they plan to use the drug. So, yes, we do have a competitor. You asked about the competitor. Competition is good, right? It builds awareness in this marketplace. But we have, we think, a competitive advantage, not only being first, but having best profile. So, we think we'll dominate this category, no doubt.
Questions from the audience? Yeah.
Congratulations.
Thank you.
I have a question about Niktimvo, which for chronic GVHD.
Sure.
I think you mentioned that you frequently give it.
I think that you mentioned that you frequently give it over a period of time.
Yes.
Do you see continued response or do you see some of the organ systems failing to respond or becoming resistant to that therapy, which has happened with other kinds of therapy like this?
It has happened with other therapies. I think our experience thus far has been somewhat unique in the sense that we had, in our clinical trial, a pivotal trial. We had the highest rate of response, and it's a little tricky how they score these responses. In GVHD, as you probably know, it's multi-organ. You can't deteriorate in any one organ or you lose your response, so you really have to maintain a multi-organ response metric for a long period of time. And that's challenging. We've been able to do that, and that's why we can be confident that patients are benefiting, and I think the key marker for benefit is, are they staying on drug? Are physicians keeping them on drug? and we dose patients every two weeks with an IV or once a month, and so we have a dose every two weeks that's approved.
We've shown data that allows patients to stay on, go on for once a month. So, I mean, what we've seen so far in the commercial practice is about 70%, 80% of patients are still on drug from launch. So, we're talking about 11 months. We expect, and we've seen in our clinical trials, patients on for three years plus, like a lot of patients. We're talking about a very high portion of the patients on for many years. So, that's, I think, the proof here. I mean, if they're not benefiting, physicians are going to take them off therapy. That's the unfortunate thing in GVHD where patients tend, they go on therapy, they need therapy, and then they lose satisfaction with those therapies because they stop working, become resistant, what have you. So, they need new therapy.
We're offering something new with a new mechanism of action that enables that. So, so far, it's been going quite well. It's supported by the clinical data that we have generated. And we expect that to manifest in the real world as well.
Great. Thank you.
Thank you.
Questions from the audience? So, on Niktimvo, you alluded to that ASH presentation, which I thought was pretty interesting on the monthly dose versus the every two-week dose. Where is the monthly dose in the treatment paradigm? You obviously have the label for every other week, but the docs seem open to using it in certain situations.
They are open to it. We explored it in our pivotal trial. It's not in the label, but what I can say is that we've had data. We've followed up with data, and we presented that at ASH. It's very supportive of a monthly dose. It's essentially the same dose that we give every three weeks that's approved, just twice as much, right? It seems to be safe and effective to the physician, but so far, it's a convenient dose, and it's something that they're starting to use more regularly in clinical practice.
And then in terms of line of therapy for Niktimvo, where are you third, fourth? Are you seeing any movement into second?
We are. I think primarily we're penetrating fourth line as a new agent in this category. It's approved for third line plus. I think the majority of use is in fourth line, which is a great place to start. There's high unmet need. And there are plenty of patients to start there. We're also seeing use in third line. So, we expect that to build in 2026 as we penetrate more fourth line, third line. And we are seeing some second line. Jakafi is approved there. So, that's standard of care. I think what will drive utilization in earlier lines is, of course, combination data. And we're generating that in our clinical trials. I mentioned them in my talk. Those will read out over time. But I think physicians are very keen to combine this new mechanism with an existing mechanism to generate better responses in this disease.
So, that will build over time. So, today, it's mostly third and fourth line. But I think over time, that'll build to second line.
This IPF data is coming pretty quick, yeah.
It is.
Maybe you could walk us through what gives you confidence mechanistically on IPF and how you think about kind of FVC as a win scenario, FVC, right?
FVC. This will be a new mechanism of action. CSF1R inhibition affects specifically the macrophages and monocytes, which sit at the nexus between inflammation and fibrosis. By downregulating that, not eliminating it, but downregulating monocytes and macrophages, you can really have a controlling impact on fibrosis as well as inflammation. We see that in GVHD. We published some data in bronchiolitis obliterans syndrome, which is a subset of GVHD, has similar pathophysiology to what we see in IPF. That gives us a lot of confidence. You see these profound effects on patients who have lung disease where we've measured FVC and we've seen improvements in FVC, not even a slowing of decline of FVC that we see with the drugs and IPF that are currently approved. We feel like we can make potentially a big impact in this disease.
The drug was actually first developed preclinically as an IPF drug. We moved into other indications. But we have very compelling preclinical data in IPF that support not only what we've done but what we've done in GVHD, but also what the clinical data tells us specifically about the mechanism of action. So, we have a great deal of confidence. We've designed a fantastic trial. The team has put something together that we think is very robust, a 135-patient trial looking at the endpoint of FVC on 26 weeks on top of standard of care. So, this is as close as you're going to get to a pivotal trial design. And we feel that this will give us a really good indicator of whether this drug will work in IPF. And we're not creating any shortcuts here.
This is a really important readout for us in the second half of the year.
Okay. Any final questions from the audience? Thank you, Michael.
Great. Thank you very much.