My name's Jonathan Chang. I'm part of the Leerink Partners Equity Research team. It's my pleasure to host the management team of Syndax. We have with us today CEO Michael Metzger, CFO Keith Goldan, and Head of R&D and CMO Nick Botwood. Thank you guys very much for joining us today.
Thanks, Jonathan.
Thanks.
Good to be here. Thank you.
Would you like to please just briefly introduce the company?
Sure. My pleasure. Syndax is a now commercial-stage company with two products in the market, one for AML and ALL. It's acute leukemia directed at the menin class of target. Recently approved in the last year plus, we've had two approvals, one in KMT2A for adults and pediatrics, and NPM1 most recently, which is, you know, is the second indication. We've launched that drug with nice success in its first year and really building very well into the market, helping a lot of patients. Second drug was also approved in 2024. It was launched in early 2025. It's Niktimvo, and that's for chronic GVHD, third line plus patients, monotherapy, adults and pediatrics.
Off to a very good start, helping lots of patients as well, and looking to expand both drugs into their markets or first and best in class, as positioning. We're in a really good place to build both the acute leukemia market around KMT2A and NPM1, as well as with GVHD, CSF1R inhibition and expanding that to other indications.
Understood. Thanks for the intro. Let's start with the commercial experience to date with Revuforj.
Right. Revuforj, as I mentioned, first indication was KMT2A, second indication was NPM1. First year sales, $125 million, fourth quarter recently reported was $44.2 million, growing very well throughout the year. Certainly, fourth quarter over third quarter growth was 38% in revenue, 35% in scripts. We're seeing great expansion and penetration both for KMT2A, very high on medical need. NPM1 has started to meaningfully contribute to the new patient adds that we've seen throughout the year, and we expect that to be a very meaningful contributor in 2026. I'd say for KMT2A, as we add more patients and contribute, you'll see the ability to bring patients through transplant and then put them back on maintenance.
That will continue to stack revenue, as time goes on. This is, we think, a big growth area for us as we continue to penetrate these markets. That's the review for Revuforj and for Niktimvo. First year, not quite complete, 11 months, $152 million, $56 in the fourth quarter alone, about 22% growth from the prior quarter and, you know, growing meaningfully into 2026 as well. Great momentum on both products and really resetting category economics as we've kinda been able to really reach new patients and add something new to the market.
Great. How should we be thinking about 2026 for both of those products?
Right. As I mentioned, for Revuforj, key drivers for us are continue to penetrate KMT2A, where there's really you know, as Revuforj has become standard of care, really treating patients as early as possible, call it second line, and third line is where the majority of that business is. Then for you know, for patients going to transplant, putting them back on maintenance, that will be a real driver of growth as we penetrate into this market. Then NPM1, same, really just new patient adds, keeping patients on drug, bringing them to transplant as well if it's merited and warranted. It's really a you know push with a differentiated profile into this space and bringing it to as many patients as possible.
Got it. Did you wanna touch on the?
The Niktimvo as well? Sure. Niktimvo is really made its mark so far as third and fourth line. It's well penetrated now in fourth line. We're talking about 6,500 patients, third line plus. We penetrated about 20% of third line, very meaningful in its first year. It's a new mechanism, so it offers something new for GVHD patients. We expect to continue to penetrate third line very meaningfully in 2026. We have data coming in combination for both in 2027 and in 2028, which will unlock the rest of the market opportunity. Something similar for Revuforj, and that will have that opportunity to get to front line, we believe first, but for GVHD, sticking with combinations, getting there in 2027 and 2028 to unlock that total market opportunity for us.
Got it. Maybe just double-clicking on Revuforj, what are the key learnings today in terms of how long patients stay on treatment, and how do you see that, you know, evolving in the future?
Very important question. I think we've guided in the first year. We said that duration of therapy was gonna be about 4-6 months, and we hit that. We feel very good about where we were in the first year. As I mentioned earlier, the key is to treat patients as early as possible in their journey. Usually by doing that, you increase the odds that they'll get to a response, and when they get to a response, they tend to be able to go to transplant, at least for KMT2A patients. That's an important goal. Then you will bring them back and put them on maintenance therapy once they clear their transplant.
We've seen those dynamics in year one. As we've had treated patients earlier and earlier and in combination, and that will continue to build throughout 2026. Duration of therapy going from 4- 6 months, many of the patients weren't really in that pool for that much of a period of time based on the fact that they were kind of off drug and then on their holiday when they were coming back for maintenance. The impact of maintenance will be felt more in 2026, and we think we'll move from 4 - 6 months more towards the 6- 12-month range as we as we get through 2026 and into 2027. That's an important goal, but I think it's, you know, very much impacted by how early you can treat the patients and then how many patients come back for maintenance.
Got it. Can you discuss sort of your efforts around physician education and your strategy for ensuring a successful launch?
Sure. I'll turn it to Nick.
Yeah. No, thank you, Jonathan, and it's nice to be here. You know, maybe just taking a step back for a second before I answer that question, you have to reflect that really the paradigm and the treatment of acute myeloid leukemia is really being transformed. This is a revolution in what has been a very difficult disease to treat for many years, and the outcome for these patients has been very poor. Since the approval of Revuforj, the entire approach to the treatment of both adults and children with KMT2A or NPM1-driven AML and potentially other mutation subtypes like NUP98r, which although we don't have approval for, is another HOXA/MEIS1-driven mutation.
The approach to the treatment of these patients has completely transformed both outcomes and the way physicians are thinking about treating them. We have an extensive in-house program and also working with key advocacy groups like Blood Cancer United, who we have a very positive collaboration because we think it's really important that we educate healthcare professionals in how to manage patients given this new treatment modality, which is novel and really impactful. You know, from our perspective, we support a lot of continuing medical education. We have a big medical team in the field educating on the optimal treatment of these patients.
Perhaps most importantly, we want to ensure that we have a really strong presence and are providing data at key congresses that physicians and other healthcare professionals in the treatment of acute myeloid leukemia can have the opportunity to review the data and see it. I think ASH last year was a great example of that. We actually had 23 abstracts as a company at ASH. Over half of those were on revumenib. The rest were on axatilimab. We're anticipating a leading presence through all of the major congresses in 2026, so ASCO, EHA, ASH.
It's really important that we're educating physicians on how to treat, patients, you know, how to select patients, how to diagnose patients, that we know there's a lot of clinical interest, even though it's not technically on our label, treating patients with a combination of therapy because we've generated such compelling data in combinations. Importantly, if a patient does get to transplant, how to manage them subsequently. This is not an area we're promoting. This is a clinical practice consideration. In the interest of clinical practice, generating data to support how patients manage tolerability and duration of therapy with revumenib after a patient has had transplant, is something we're really focused on and we think is very important.
Understood. Can you discuss, I know it's early days, the experience in the NPM1 mutant patients to date on the commercial side?
Sure. We had said that throughout the year of 2025, I think we noticed that about 10% of our business was not KMT2A, so NPM1. That really built through the third quarter as we did a little bit of a look back. We saw that portion of the business in terms of new patients grow to about 20% as we got guidelines in September, and then we had approval in October. Fourth quarter was it grew to about 30%+. Well, 30% plus is basically at least 30% of the business. New patients was NPM1.
That's now becoming more meaningful overall, and we expect that will continue into 2026 as we haven't given a sort of a target for what percentage of the business that'll be, but it should be a very meaningful piece of the business. It's a bigger population, right? NPM1 is about twice the size or maybe two and a half times the size of relapse refractory. KMT2A is about 2,000 patients. We're talking 4,000-4,500 patients in relapse refractory NPM1. It's a larger patient population, so we should be able to penetrate that meaningfully, have dominant share in that setting as well. That's what we're looking forward to in 2026.
Got it. Do you anticipate a different experience for the patients depending on the genetic mutation that they have?
I mean, outcomes are different for these patients. KMT2A patients tend to be younger. They tend to be fitter patients. They have, you know, a very poor prognosis. For those patients, the ambition really is to try to get those patients to a transplant. That gives them the best outcome. Even in relapsed refractory disease, that gives them the best possible, you know, chance of a really durable remission. In NPM1, again, you do wanna try to get patients to transplant, but some patients will just remain on therapy if they're doing well. This tends to be a more elderly, less fit population, so sometimes you wanna continue a patient on if they go into a remission and they do well.
We showed in our AUGMENT-101 study that, you know, just under half of the patients actually did have a response, which is really encouraging. We know that in those patients that respond, their median overall survival is very encouraging. It's nearly 2 years. That's a significant shift in, you know, historical expectations where median overall survival for these patients was of the order of 3 months. If you can get a patient response potentially by combining with either a single agent or a combination approach, then that's really advantageous. For both subtypes and indeed other subtypes like the NUP98r subtype, which we've generated, you know, quite interesting data in. Again, this is a relatively rare subtype with very poor outcomes.
We have shown in a series of patients that those patients also get quite high rates of MLFS, and we'll be presenting more data this year on other interesting subtypes with a common HOX/MEIS1 pathway driven disease.
Got it. How do you think about the size of the relapse refractory AML market and help us compare it to how you view the frontline market?
The population of relapse refractory, I think I touched on it before, about 2,000 patients KMT2A, and about 4,000-4,500 NPM1. That's, you know, call it 6,000-6,500 patients in relapse refractory. When you expand to frontline, you're talking about with roughly 20,000 patients AML, another 6 or so in ALL. You're talking, you know, in the order of 9,000 patients frontline split roughly 50-50 between unfit and fit. It's obviously a larger population. Unlikely you'll treat you know, a second time with a menin inhibitor. You might. Yeah, and there's some cases where that does happen.
Essentially frontline could be as much as, you know, $5 billion-$7 billion in total addressable market if you factor in both price, as well as, you know, 9,000 patients. Then really a big driver of size of market is, you know, how long they stay on therapy, right?
Mm-hmm.
In relapse refractory, you have one, you know, set of assumptions. In the frontline, you're looking at, you know, perhaps a year to two years of therapy, which could really extend the total addressable market to many, you know, billion dollars.
Got it. Can you discuss your strategy for getting to frontline and what are the associated timelines with that?
Yeah, sure.
The strategy is well-defined now. We're focused on execution. We have two pivotal studies, one in patients that would be considered fit for intensive chemotherapy. This is the REVEAL newly diagnosed study. That study started at the end of last year. We're busy activating sites, getting the study up and running. It has dual primary endpoints of event-free survival and MRD negative CR, 'cause we think that could be an important surrogate endpoint for predicting event-free survival. We're laser focused on executing that. That's an international study. We'll have a lot of study participants worldwide in the expectation of it recruiting quickly, and it being the first to read out for fit patients. The other important study we have in the frontline study is called the EVOLVE-2 study. This we're doing in partnership with HOVON.
That has proved to be a very fruitful collaboration. This is a leading academic group with a deep experience in treating these types of diseases. That was actually the first study to enroll a patient in the frontline setting, so we were the first out of the gates in Q2 2025. We have a high number of sites now activated. Again, it's an international study. We'll be including sites in the U.S. It's enrolling extremely well. We're happy with the progress of that. Again, that study has dual primary endpoints, in this case overall survival, which is the gold standard obviously for these types of studies.
We've also included complete response rate again as a surrogate endpoint that we believe and has been shown to correlate very well with overall survival and has been used in the past to support accelerated approval. We're confident about the execution and the design of both of those studies. Our expectation is to be the first to have a study to read out. Most importantly, our expectation is to have the first approval, which is really the ultimate goal to make the therapy available to patients with newly diagnosed AML in combination with standard of care. We're making good progress with both of those programs.
Understood. As we think about combinations with standard of care, can you discuss the combinability of Revuforj?
Yeah, we've shown it to be very combinable, and I think there's a number of reasons that revumenib is attractive as a menin inhibitor that you can use. The first thing is we've generated the most extensive data sets both in combination with intensive chemotherapy, and we presented these data at ASH last year from our 708 study, which Syndax is sponsoring, and also a very productive collaboration we have with the NCI, and showed the drug is well-tolerated at recommended doses, the 160, 270 dose. We showed very high rates of complete response rate and importantly MRD negativity with high proportion of patients subsequently going on to get transplants. Those were very encouraging.
We've also generated a lot of data in combination with ven and hypomethylating agents, which gives us a great deal of confidence in our EVOLVE-2 study. It's combinable at standard doses. It's tolerable. We don't see any significant PK interactions with currently approved standards of care. Importantly, you don't need to dose adjust for common concomitant medications, specifically H2 antagonists or PPIs or other medicines that these patients are commonly on in this setting because there's no drug-drug interaction in terms of gastric pH, which makes it a very attractive drug to combine. Now we're just focused on the execution of these frontline studies and hopefully getting a positive readout and then filing them and getting the drug available to patients.
Understood. How are you guys thinking about opportunities for Menin inhibitors beyond leukemia? Go ahead.
Yeah, no, it's exciting, and we were excited through our collaboration with John Crispino and his lab to present a best of ASH abstract last year. That was a collaboration looking at myeloproliferative neoplasms, and there's a compelling hypothesis in terms of targeting megakaryocytes for MF, and showed in vitro and in vivo models, both as a monotherapy and in combination with a JAK, the potential to impact the course of the disease within myelofibrosis.
We are this year, you know, as the leaders in this space, working with some of the top collaborative groups working in the myelofibrosis space, and we'll communicate later the setup of some early phase studies to explore the potential of Revuforj as a monotherapy, but also in combination in patients with myelofibrosis, and we're excited about that potential life cycle management opportunity.
Got it. Your efforts beyond leukemia also are Revuforj, correct?
Revuforj in myeloproliferative neoplasms, specifically myelofibrosis, yep.
Got it. Understood. You mentioned you wanna be at all of these medical meetings. Have you guys commented on, like, what specific updates investors can expect at each of these meetings?
I mean, we'll be very active. I mean, you saw our presence at ASH this year was up significantly from last year with, you know, 24 different presentations. I think we'll have major presence at EHA, major presence at ASCO, and then of course, at ASH later in the year. We've talked and Nick mentioned sort of our frontline plans as we enroll our frontline studies. We'll have a lot of real world data, which also support things like maintenance and some of the combination use and how we think about the robustness of the profile and how do we deploy that or allow physicians to see how it's deployed, not only at a trial basis, but also on a real world basis.
We have updates coming in some of our ven studies with the SAVE study and a Beat AML study looking at newly diagnosed patients following those cohorts and new additional patients enrolled. Those updates will be coming at some of these medical meetings. Of course, the chemo combo in newly diagnosed patients, the phase Is will be updated. There'll be lots of real world data, also updates to existing studies and we should be active at all of these congresses.
Understood.
Anything else to add to that, Nick?
No, I think that's great. Yeah.
Yeah, you know, I would also say, I mean, we haven't talked about it yet, and we get to Niktimvo, but, relative to an IPF trial that's reading out. I don't know if you have questions about that.
Please.
Yeah, maybe I'll mention it. Yeah.
Let's double click. We'll switch now.
Sorry, I just went there. Niktimvo, you know, one of the adjacencies when we think about life cycle, we're running a phase II proof of concept trial in IPF, which, you know, 135 patients, fully enrolled, and we recently announced that on our quarter, and we'll have data in the fourth quarter of this year. That's an important new trial will be reading out in terms of milestones. That's one to look for and, you know, exciting new area for CSF1 inhibition, to be there and a lot we've learned from our early work in GVHD that we think relates very nicely both from a disease standpoint as well as a, you know, opportunity for to go into IPF.
Got it. Can you talk about the opportunity associated with that expansion? I think we discussed some of the more near-term metrics earlier in the discussion. How do you see the long-term potential for this drug?
Niktimvo, of course, in GVHD, we think it can be a billion-dollar-plus opportunity. As you expand to frontline, it gets to be a larger patient population. I think the IPF opportunity is a whole order of magnitude different in terms of 150,000 U.S. patients plus. I mean, there's a lot of unmet need there, and this would be a new mechanism for those patients. The ability to extract meaningful data from this trial and then, of course, apply it to a phase III trial that would come thereafter if positive, that's kind of the next step there.
It's a, you know, very meaningful market opportunity and again, it would be the first, you know, use of this mechanism in that disease where there's just high unmet need.
Understood. How are you guys thinking about business development opportunities for the company?
That's how we built our business, right? Our model is to in-license and develop or acquire and develop. We've built robust capabilities for development. Nick and his team can take an early molecule all the way through approval. We've proven that we can do that. We'll be focused on oncology. We are focused on oncology. We'll remain focused on oncology. I think the opportunity is to bring additional molecules in. We keep a very high bar, but that's in our lineage. Ultimately, over time, we look to build the pipeline through additional business development.
I think right now we're completely focused on what we have and building value around these two very successful molecules, which as we talked about today, there's lots that we have on our plate in order to get to frontline and really expand the opportunity set even to some of these adjacencies like myelofibrosis and then get into IPF. There's a lot we can do, a lot of value to build, but business development remains a longer term objective for us.
Got it. How about business development the other way around?
Same going in the other direction.
Oh, in terms of, like, maybe finding a partner.
Yeah, yeah
or something like that? Well, I think, look, we're in a unique position as a company where we've built a lot of value. We have global rights to Revuforj. We have a partner in Incyte with Niktimvo, so that's 50/50 partnered in the U.S. They have a license to the drug to develop and commercialize outside the U.S. We've seen the power of partnering, and they've been a fantastic partner for us in GVHD specifically. We expect to be able to expand that through international work with them. Revuforj at some point in the future, you know, getting into international markets, sales and marketing, that's not our business. It'll be somebody else's business. We could look to partner long-term objective.
I think getting these trials done, register the drug in these other geographies, that's stuff that we can do and do well. Ultimately, I think there'll be a commercial partner for that drug down the line. Today we're very focused on what we can do ourselves and have the resources to do that.
Understood. Let me check, see if there are any questions from the audience. How should we be thinking about the road to profitability?
Yeah, good question.
for you guys?
Keith.
Yeah. Thanks for the question. We're in a, I think, a unique but fortunate situation. There's not a lot of mid-cap biotechs that have the opportunity to launch a drug, period, much less two drugs in a couple months' time. With the successful launches of both products last year, they're both generating meaningful gross profit contribution, helping us offset the development dollars that we're spending, expanding the labels, bringing both drugs into the front line. We've made the statement given guidance that we have enough cash to get to profitability with the current balance sheet we have. We ended the year with almost $400 million in cash and equivalents, and we've made the commitment to keeping our operating expenses flat.
With the contribution from both drugs, flat OpEx, we're clearly on the road to profitability in the pretty near term.
Got it. Was there a timeframe for that?
I mean, we haven't guided on the timing of that, but you know, if you look at our quarterly cash burn in 2025, you'll see a pretty significant decrease quarter by quarter throughout the year. It's pretty easy to model out and draw the line to that gets us to profitability.
Understood. I think that's it then. Thank you guys very much for taking the time.
Thank you.
Thanks, Jonathan.
Great to be with you.
Thanks to Leerink.