Oh, okay, great. Thanks everyone for continuing to join us here at one of Guggenheim's biotech conferences. My name is Brad Canino, senior analyst. Very happy to be sharing the stage for the next fireside with Syndax Pharmaceuticals, Michael Metzger, CEO, Nick Botwood, CMO, Head of R&D, Keith Goldan, CFO. Thank you so much for joining us. Maybe Michael, kick it off with a quick intro.
Great, Brad. Thanks for having us. Great to be with everybody and get back on track in the new year. Just been a fantastic start for us. We pre-announced our earnings last for the fourth quarter, and it was truly a standout year for us from a revenue perspective on both products, both expanding meaningfully and making sort of setting a new bar in their respective indications. For Revuforj, $125 million in annual sales, net sales, growing quarter-over-quarter very nicely. For Niktimvo, $152 million in the first 11 months of being on the market in chronic GVHD, and also a very nice quarter-over-quarter growth. So both franchises going well.
The state of play in terms of development of both of these franchises for lifecycle really pacing well, and we'll have lots of milestones and things to talk about for 2026 as we continue to expand both of those franchises meaningfully. And we'll have new areas to talk about, like IPF, and I know there's some questions about that relative to Niktimvo this year. So really exciting place to be at with Syndax for 2026.
Okay, great. So you pre-announced revumenib growth, 38% in Q4. That accelerated and was a step up from Q3 of 2025. Talk about the drivers of what led to that?
Right. So, we've talked about KMT2A, that was our first labeled indication. And then in the fourth quarter of last year, we had first we had NCCN guidelines for NPM1, and then the approval in October. So that those are two interesting and important pieces of the business. For KMT2A, that's a continued build of that and with a penetration into new patients, as well as, as, as many of you know, these are younger patients. They tend to are in dire need of transplant, high unmet medical need, very poor prognosis, and with their age and their fitness, physicians would like to take them to transplant, Revuforj enables that in a way that no other drug has been able to do that to date. And so we're having you know, I, I would say, great penetration into that marketplace. That will continue.
Certainly, patients going to transplant with treating them earlier and earlier, not third, fourth, fifth line, but we're talking about second and third line, predominantly in, commercial practice. And now you have the ability to bring them back on, post-transplant maintenance, which continues to build. So those, those will be the important drivers for KMT2A and NPM1. New indication, great momentum, great awareness around the profile. What we did at ASH this year with data is, you know, certainly getting the approval, but also, combinations and seeing how the, the, real-world data looks like with NPM1 as well. So great awareness, great, anticipation for the launch of that drug into fourth quarter, and we saw a meaningful impact, and uptake there.
And so we'll be updating and giving more, some more detail on that as we get into our fourth quarter call. But really a very very important piece of the business coming on now in NPM1, as well as what we've seen in KMT2A, and that'll continue to build.
Okay. And how has that momentum of the maintenance and the new indication carried forward into the first month of 2026?
Continues to go very well. I think we'll say more on our call, but I think we're very excited about what we're seeing and believe it'll continue to be, you know, a big driver throughout the year, but certainly off to a great start.
What market share do you estimate you have in NPM1? As you see that market maturing over the next few years, what do you expect to maintain?
Too early to tell what market share looks like just yet, but we're certainly very encouraged by what we're seeing in terms of early use of the drug. As I said before, great awareness and anticipation for what Revuforj can bring to NPM1 patients. Best-in-class profile, very strong efficacy, and so physicians are anticipating using it across their patients, and we've seen that. And so, we expect to be dominant. I mean, I think that's as clear as we can say it. We expect to have dominant market share in this category, as we've had for KMT2A. We own KMT2A. We expect the same for NPM1.
In KMT2A, what rate are you up to of the percent of transplanted patients who are now receiving revumenib maintenance in the commercial setting? And where do you think that can still grow to?
Right now, we're in third quarter reported 35%-40%. Those are. That's the percentage of patients who have come back for maintenance of those who have been transplanted. We expect that to meaningfully grow over time, and when I say meaningfully, it could grow to as much as probably 70% to 80% of patients go on to maintenance at a steady state. It's not gonna happen overnight, but will continue to meaningfully grow as, again, you treat more patients earlier, it sets them up well for their, for their potential transplant, and then the opportunity to come back on maintenance.
It's also part of this is education, right? Physicians w e're talking to all the physicians, so it's not just the academics and people who treat a lot of the leukemia patients, but also in the community now, and giving them an explanation of how best to, you know, deploy the drug in maintenance from a dose perspective and so forth.
So there's data that we'll be putting out this year at the medical conferences, and Nick and his team are working very closely with leading physicians to put out real-world data that supports maintenance use and is really educational for physicians and allows them to understand how best to use the drug.
I think that is a building phenomenon, and one that, you know, with a new drug and a changing paradigm in this disease with Revuforj, it takes—it does take some time to build that understanding, but we're excited about that.
Okay. So it's headroom to double that, uptake still. But how much of that dynamic, you mentioned time, can play out in 2026, and how much will need potentially more time beyond that?
W ell, I get, I can say that in 2025—what we saw in 2025, and what we'll see in 2026, we've seen a steady progression. When we started, it was 25% to 30% of patients on maintenance, and that grew to the next quarter by another 5%. So we've stepped up each quarter. So I expect that it will continue to build over time. It's hard to predict the future, but I do believe that we will get to that steady state 70%-80% over future quarters, but not right away.
Okay. I mean, AML being such a desperate disease with unmet need, what would cause a physician to start using maintenance later in patients that maybe they transplanted this past year but didn't use maintenance? What gets them to use it later? What's that learning element for them?
Nick?
Yeah, sure. I think it's, and thank you, Brad. It's nice to be here. I think it's to do with allowing for, you know, engraftment and just allowing a period of time for patients to recover before you start a maintenance therapy. So from experience, it tends to be about 60-90 days after transplant for a patient to recover. The patient will then be considered to go back onto maintenance. There are a number of considerations I think that would drive a physician's desire, their genetic subtype. Clearly, patients that tend to relapse, like KMT2A, very high desire to treat, whether they have MRD positivity and a degree of patient choice as well.
But what we're seeing is with increasing learning and increasing data, and we'll have more data this year, already presented data suggesting that driving a patient onto maintenance after their HSCT gives them a much better chance of a durable remission. So there is that willingness to do it.
If you get to that overall rate, what does your data show about the potential length of maintenance that these patients will receive in terms of treatment duration? And then what does that bring the overall book of business up in terms of an average treatment duration for KMT2Ar?
I mean, I could maybe say that talking to physicians, their intent is to treat for somewhere between 1 to 2 years. That seems to be the, the desire. The duration of therapy is impacted a little bit by how well the drug can be tolerated and how well the patients can be managed. All of the patients after transplant are somewhat fragile. After engraftment, they have a tendency to cytopenias and other things. So there is a, there is a, a growing awareness that you need to manage dose quite carefully, sometimes give them a small dose interruption. With that growing knowledge and starting at the right therapy, starting at the right dose, then I think the, the ability to maintain a patient on therapy is gonna become more.
As we see more efficacy data, particularly these kind of durable remissions, we saw the first evidence of that at ASH in that pediatric series from MD Anderson, where 90% of these children were alive at one year, which is really quite a different level of efficacy than you'd expect from historical controls. You know, the patients will be managed better, and as I say, the intent is 1 to 2 years.
Yeah, I would say 1-2 years, and just to add on in days of therapy overall, KMT2A, I think we said first year, we're looking at, in just the overall population, we're treating 4 to 6 months duration of therapy. That's, of course, impacted by how many patients go to transplant and then how many patients come back and for how long they take maintenance. And so in a second year and beyond that, we look to go more towards 6-12 months duration of therapy on average for patients. But again, it's going to be impacted significantly by how many patients come back and how long they stay on maintenance.
Okay. And now, with revumenib beyond AML, what supports the thesis for MPN development, and how will that story unfold at Syndax?
Very important, and I'll turn it-
Well, yeah, we were excited about this, and I think it speaks to our leadership in the science of menin, that we had this collaboration with John Crispino's lab, which got Best of ASH. This was a very compelling preclinical model looking at myeloproliferative neoplasms, of which myelofibrosis is one, in vivo and in vitro models of mice. There's a sort of compelling hypothesis for menin in MPN disease, linked to HOX genes and upregulation. You get this epigenetic upregulation and that leads to fibrotic megakaryocytes, abnormal platelets, and splenomegaly. In these preclinical models, we saw that revumenib, both alone and in combination with Jakafi, can really impact the underlying pathology of these myeloproliferative neoplasms.
So we have obviously now working with leading centers and leading academics in the field of myelofibrosis and moving very quickly into the clinic, in collaboration with them, exploring the role of revumenib and menin inhibition generally in myelofibrotic patients. Initially in more relapsed refractory disease, but we rapidly want to move into frontline in combinations, and that's something that we're building on. So I think you'll hear a lot more. You will hear a lot more this year about those studies that we'll be starting, but we're excited about that lifecycle management opportunity for Rev and the menin class.
Okay. All right, we'll spend some time now on Niktimvo, maybe just to start where it's currently approved in later-line chronic GVHD. What do you see as the peak opportunity in that setting? And then how should we think about the value that flows to Syndax with that type of opportunity?
Right. Maybe I'll take the first part and maybe turn the second part to Keith. But look, I think this is a very important indication. Third-line plus 6,500 - about 6,500 patients in the U.S. If you get to the front line, we're talking about more, about 17,000 patients, thereabouts, in the U.S. And so very meaningful third-line plus 6,500 patients. We think this drug can be approaching, you know, $1 billion in third-line plus, and certainly more as you get front-line indications. And so it's potentially in GVHD alone, you know, a multi-, you know, $100 million-dollar, multi-billion-, or potentially a billion-dollar plus drug opportunity.
And then in terms of our relationship with Incyte and how the collaboration works and how the revenue flows, and maybe, Keith, do you want to address that?
Sure. Thanks, Michael. So we in the United States have a 50/50 commercial profit split with our partners at Incyte. We co-promote the product, so both companies have field teams actively promoting Niktimvo. So the commercial profit split is based on the net revenue that Incyte reports, less all commercial expenses. So that includes any royalties payable to UCB, where we originally licensed the drug from, cost of goods sold, and 100% of commercial expenses. And then that net commercial profit is split 50/50. In the first full quarter of sales, we were already showing a net commercial profit from that product. It's an extremely targeted customer base, so it's a very profitable drug to promote.
We've given guidance that we expect to report about 25%-30% of whatever the net sales number that Incyte reports, dropping down to our P&L, as collaboration revenue.
Okay. And what else-
If I could just add, that 25%-30% is kinda current steady state. We would expect that over the long term to grow significantly because we're gonna continue to grow the top line net sales, and we have a relatively fixed commercial operating expense base.
Yeah. Well, that somewhat bleeds into the next question, too, is what else is Incyte doing to build value for Niktimvo in GVHD? And when will we start to see data for that, to see if it's potentially gonna expand that opportunity?
Right. So I mentioned the earlier line trial. So they're running a trial, Incyte's running a trial, in combination with Jakafi, Jakafi, which is gonna read out in the early part of 2027. So that's a phase II trial. Could be guideline-informing, potentially approval, but you know, right now, we're assuming that it's at least guideline-informing. That's an important trial. And then the other randomized trial is a phase III trial in combination with steroids that will read out in the early part of 2028. So those are two very important regimens that could really solidify us to take advantage of the full and really unlock the full opportunity within GVHD. Of course, Incyte has rights to the drug outside the US, so getting the drug approved in ex-US markets is firmly on their mind.
That will be something that will come in the near term as well, we hope, based on the trial that's been run, but also some of the things that we're working on, such as the steroid trial.
Great. And now, you at Syndax are working on the IPF phase II. You've discussed the parameters-
Yeah.
A nd critical function of that trial that you expect to read out in second half 2026.
Yeah.
Yeah, very excited about this trial. I have to say, there's a lot of supportive science that suggests that CSF1R and CSF1R inhibition could have a very important role in IPF. Everything from preclinical bleomycin-induced mouse models to significant impact we've seen on inflammatory cytokines, IL-10, TNF, TGF-beta, and then compelling data from our AGAVE-201 study in patients with bronchiolitis obliterans syndrome. So this is the the pulmonary manifestations of GVHD, wherein, we saw, you know, a nearly 50% response rate using standard NIH criteria in those patients that got the 0.3 mg per kg, which is the approved dose of, axatilimab. So. And those patients had very significant improvement in symptom. In fact, about a fifth of those patients had a 10% improvement in FEV1.
When you combine that with some of the wound-healing effects we've seen, we've had experts in IPF very impressed with the sclerotic changes in skin and wound healing, because all of that is underpinned by the same pathology, which is essentially monocytic-derived macrophages and macrophages that drive inflammation and fibrosis. A common pathology, whether you're looking at forced expiratory volume over a second, which is a more obstructive picture, or forced vital capacity, which is what you measure in our Ax-IPF. So all of these scientific data would support that proof-of-concept study, which we're gonna read out in the second half of this year. This is a very robust proof-of-concept study, Brad. It's well-designed, 2-to-1, 135 patients, primary endpoint, forced vital capacity. It was an internationally run study. It's been well conducted.
We're gonna be applying very rigorous statistics. We have very good benchmarks to estimate what we think would be a, you know, significant improvement over currently available standards of care. It's a double-blind, placebo-controlled study, so we have no insights to the data as yet, but we're looking forward to seeing those data in the second half of this year.
Is the trial fully enrolled?
It's fully enrolled now. We're just letting the data mature. It has a 26-week readout on FVC, and so we'll look at annualized FVC.
Right.
W hich we'll model using a statistical model.
Okay. So you touched on a lot of what I want to cover in a little bit more detail, starting with the preclinical package here. Can you dive a bit more into details and, you know, maybe tie that into the generation of this molecule? Because I know it was picked up from UCB back in the day. So how does that all come together?
Yeah, I think, I mean, let me go back over some of these points, 'cause I think they're quite interesting. I mean, I think that the role of CSF1R underpins a lot of what we consider the pathology of IPF in the lung, which is really impacting, particularly macrophages, which is a common pathology. And we have some preclinical data actually looking at the role of both monocytes and macrophages in a lot of inflammatory processes associated with both GVHD and IPF. And interestingly, Brad, some of the drugs that have been approved recently in IPF have also a necdotally, there are case reports of those drugs having shown some activity in GVHD.
So it's kind of interesting that that really supports the biology being consistent between the two, and we know that CSF1R is very impactful in the multisystem disorders that is GVHD. And again, when you can actually see those inflammatory fibrotic lesions, which are sort of sclerotic skin changes, and we have some very impressive pictures of patients that have skin manifestations of GVHD. When you see those really, you know, the inflammation going away and the wounds healing, those are very similar pathologies 'cause we've looked at the monocytic and macrophage infiltration of those lesions. That's a very similar pathology to what you see in IPF. So I think there's a lot to think about as being supportive, as well as those pulmonary symptoms, those patients with bronchiolitis obliterans syndrome clinically in AGAVE.
So, which showed really quite dramatic improvements in both FEV1 and symptoms. So we will see. It's a proof of concept study. We are certainly planning for success, by which I mean we're doing all of the pre-work to plan for a potential phase III should we see the signal that we would hope to see from that proof of concept study. So if we do see a signal, we'd be well set to undertake a phase III in IPF.
Yeah, I'll just mention that you did mention UCB. So we did in-license the drug from them, and sometimes you return to some of your early work that you do. And UCB intended this drug to be used for IPF, but back when it was first put together, they decided that it was probably better suited to go into oncology. They are not an oncology company, so they licensed it to us. But the data in IPF, as Nick mentioned, is extremely compelling, and the sort of connection through GVHD kind of led us back to IPF. So it's kind of interesting how it's worked out.
Yeah. And you keep talking about these symptoms in the GVHD patients and in the FEV. How do we make that translation, though, from a clinical endpoint of improving shortness of breath and FEV to the FVC endpoint in an IPF patient?
Yeah, it's t here's somewhat, I mean, they're different measures. One reflects a more obstructive pattern that you get in GVHD. Idiopathic pulmonary fibrosis is associated with a more, a more restrictive pattern, which is why you look at FVC. So they're slightly different measures, but they're actually underpinned by a very consistent, sort of pathognomonic signal. And so we have evidence to show that the, you know, the, upregulation of both, monocyte-derived macrophages and macrophages themselves, which drive the process, is common to both, which is inflammation and fibrosis. These are common effects. like, It's a very good and consistent analogue, and, and therefore, it's very reassuring again, to have seen these agents, like nintedanib or pirfenidone, actually show activity in GVHD. It shows that kind of they're relevant. Even though they're different measures, they're both underlying lung pathologies.
So yeah, I think, I think we'll wait and see. It's a proof of concept study, but I think there's good evidence to support that this we might see a good result. And frankly, there's such an unmet need in IPF. You know, even when you look at recently approved drugs, you know, the overall benefit clinically is relatively modest. You're looking at a relatively modest slowing of the deterioration in pulmonary symptoms. Our hope would really be to try to stabilize patients with their disease, improve their symptoms, and may potentially even improve mortality because these patients have, you know, relatively short life expectancy, unfortunately.
Yeah. Is there anything unique about the specific way Niktimvo inhibits CSF1R? Obviously, there are a lot of oral inhibitors, some other antibodies in development. Is there anything unique about that approach, or is it just the CSF1R needs to be inhibited?
No, there are some unique features to the antibody in terms of the molecular configuration of the antibody. It has some fairly unique features, and we know from you know, both our preclinical work and the clinical work we did in AGAVE-201 and the different doses we looked at, and we saw actually the most efficacious dose was at the lowest dose we assessed, with the 0.3 mg/kg. And I think that speaks to the arms of the antibody itself, which is a unique configuration, and I think that speaks to its potency and the activity we've already seen in its approved indication, which should translate into IPF.
Okay. How is Incyte currently involved with any of the IPF development? If the data do support further development, how will that be funded and operated between the two companies?
Right, so the collaboration is set up for us to share expenses. We, as part of this particular relationship, we set up the opportunity to do IPF and that we would take on the burden of this trial, specifically, and then there'll be an opportunity to go forward and share costs on future trials, and we expect that to be the case, assuming that the IPF trial is positive. So that's the i t works the same way for IPF than it does for any of the indications that we work with, with Incyte, whereas we share a 55-45, 55% for them, 45% for us. And, you know, we know they're excited about the indication as as are we, and so, we'll, you know, join arms and continue to collaborate on this one.
Okay. Maybe that'll lead me to my last question. You guys have a path to profitability as guidance, maybe components, Keith, that get you there, and then the burning question: Is that a potential in 2027?
It's certainly a potential. We're not going to be specific on timing, but I think, you know, with we're in a unique situation. We have a small biotech company with two drugs, and both launches got out of the gates really, really strongly in 2025. So with significant revenue contribution from both drugs, and I'll note that we've given guidance that we're keeping operating expenses flat at $400 million, excluding non-cash comp this year. Those two things combined certainly give us a path to profitability. We don't need any more cash. We're fully funded.
Okay, great. Well, Michael-
Good
Nick, Keith, thank you so much.
Thank you, Brad.