Syndax Pharmaceuticals Inc Q4 FY2025 Earnings Call

Good day, everyone, and welcome to the Syndax Fourth Quarter 2025 Earnings Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

Thank you, Operator. Welcome, and thank you all for joining us today for a review of Syndax's Fourth Quarter and Full Year 2025 Financial and Operating Results. I'm Sharon Klahre, and with me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer; Steve Closter, Chief Commercial Officer; Dr. Nick Botwood, Head of R&D and Chief Medical Officer; and Keith Goldan, Chief Financial Officer. This call is accompanied by a slide deck that has been posted on the Investor page of the company's website. You can now turn to our forward-looking statements on Slide 2. Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent Form 10-K as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, February 2026 only. A replay of this call will be available on the company's website, www.syndax.com, following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Thank you, Sharon. Good afternoon, everyone, and thank you for joining us. Starting with Slide 3. I'm pleased to share our fourth quarter and full year financial results following a transformational year that positions Syndax for continued growth in 2026 and beyond. In 2025, we demonstrated the exceptional strength of our commercial and R&D capabilities, successfully launching two first and best-in-class medicines and achieving our third FDA approval within the span of approximately one year. 2025 was a remarkable year for Syndax, and we have only just started to unlock the potential of our first two medicines. Let's dive into our commercial results for Revuforj. In the first full year of sales, we generated robust top line results, delivering $125 million in Revuforj net revenue in 2025 and further solidifying our leadership in menin inhibition. Notably, we ended the fourth quarter with 38% growth in Revuforj net revenue and 35% growth in prescription quarter-over-quarter, showing strong demand and momentum heading into 2026. Two main factors drove this impressive increase in demand. First, continued growth in our KMT2A business as the number of patients on therapy post-transplant begins to meaningfully stack. Second, growing uptake in relapsed/refractory NPM1 mutated AML following the FDA's approval of our expanded label at the end of October. Our launch into NPM1 is off to an excellent start, building on the solid foundation we established through our launch in KMT2A, including a robust prescriber base that has extensive experience and comfort using Revuforj. We are confident we will win in NPM1 with a best-in-class product profile, including the broadest label and unmatched efficacy data, together with strong customer relationships and excellent market access. Turning to Niktimvo and chronic graft-versus-host disease or GVHD. Fourth quarter results were strong with a 22% increase in Niktimvo net revenue quarter-over-quarter. This continued growth reflects a steady stream of new patient starts and a high percentage of patients staying on therapy. Niktimvo net revenue for 2025 reached $152 million in the first 11 months of launch, tracking ahead of the one-year benchmark set by Sanofi's REZUROCK, which reached $500 million in annual U.S. net sales within the first four years of launch in the same indication. Niktimvo's outperformance highlights its unique ability to address both fibrosis and inflammation. As we expected, Niktimvo contributed significantly to our bottom line in 2025. Our 50% share of the Niktimvo product contribution totaled $42 million in collaboration revenue to Syndax in 2025. As Niktimvo sales continue to ramp, while much of the expense base stayed largely fixed, we expect to retain an even larger proportion of Niktimvo revenue over time. Altogether, Syndax revenue reached $172 million in 2025. Achieving this result in our first year as a commercial company underscores the significant unmet needs we are addressing and our ability to execute at the highest level. We remain confident in the continued success of both launches supported by multiple growth drivers that Steve will discuss shortly. Importantly, we remain well funded to continue investing in our strategic priorities to fuel the next phase of growth. This includes advancing our life cycle and frontline programs to expand our patient impact and unlock more than $10 billion in total addressable market opportunity. On the clinical development front, we made significant progress advancing our pipeline in 2025 and recent months. In addition to achieving a second FDA approval for Revuforj, we were also the first company to initiate enrollment in a pivotal frontline trial of a menin inhibitor, positioning Syndax to be the first to frontline. We also delivered the first real-world evidence for a menin inhibitor, among many other achievements that advance our scientific leadership and the body of evidence supporting our medicines. More recently, we completed enrollment in MAXPIRe, a robust Phase II trial of axatilimab in idiopathic pulmonary fibrosis, or IPF, a disease with high unmet need, which affects a large patient population. This trial has the potential to demonstrate axatilimab's utility in IPF and provide further rationale for its mechanism in a number of diseases with similar manifestations. We've made remarkable strides advancing our mission and building Syndax into a leading oncology company with two successful commercial launches gaining momentum, important upcoming data readouts and multiple exciting opportunities for label expansions. We are positioned to make a major impact on patient care and deliver long-term and sustained growth. With that, I will turn the call over to Steve to discuss our commercial progress in more detail. Steve?

Thank you, Michael. Starting on Slide 4. Now as Michael noted, we reported strong results from our launch of Revuforj. In the first full year of the launch, we delivered $124.8 million in Revuforj net revenue, well above launch benchmarks set by other AML therapies, even though KMT2A translocations are less prevalent than some other targetable mutations in AML. As we enter year two, we expect to continue to outpace other therapies and redefine success in this space. Our conviction is supported by our recent label expansion, which enables us to now target a substantially larger population than other AML therapies as well as multiple dynamics that are expected to meaningfully extend treatment durations. In the fourth quarter, demand for Revuforj accelerated throughout the quarter, resulting in $44.2 million in Revuforj net revenue, up 38% from the prior quarter. New patient starts were up about 20%, driven primarily by uptake in NPM1, bringing us to approximately 1,050 patients treated commercially since launch. With the vast majority being KMT2A patients, we approach 50% penetration of the KMT2A incident population within the first year of launch, which really is an outstanding result. Total prescriptions were up approximately 35% from the prior quarter. The increase was driven by new NPM1 patients and continued growth in KMT2A as the pool of patients on therapy post-transplant expands. The percentage of Tier 1 and Tier 2 accounts that have ordered Revuforj also increased in the fourth quarter with more than 80% of these accounts now activated, up from 70% in the third quarter. In addition to an increase in the number of the largest academic centers ordering, the overall number of accounts ordering also increased, reflecting growing uptake in academic centers of all sizes and community practices. The growth in our prescriber base following the label expansion reflects physicians' enthusiasm to prescribe Revuforj to their NPM1 patients and positions us to drive further penetration in both NPM1 and KMT2A. Turning to Slide 5. There are multiple factors that will drive continued Revuforj growth in the near term. The first driver is growing uptake of Revuforj in relapsed/refractory NPM1 mutated AML, our second indication, which triples the size of our annual addressable patient population to a total of 6,500 patients. Our launch into NPM1 is off to a fantastic start, building on our broad and growing prescriber base and excellent market access coverage. Physicians are enthusiastic about our data in NPM1 and the results they've seen with Revuforj in their patients. Like we achieved in KMT2A, we rapidly established reimbursement in NPM1 with formulary coverage now complete at 97% of all lives covered just four months after approval well ahead of typical industry time lines. Regarding our ramp in NPM1, we began to meaningfully add new NPM1 patients following the addition of Revuforj to the NCCN guidelines for relapsed/refractory NPM1 mutated AML towards the end of September. The latest available data suggests we exited the third quarter with NPM1 patients representing about 20% of our new patient starts. That's up from our original estimate of approximately 10% across the third quarter. Now while data are still maturing, early indicators suggest that at least 30% of new starts in the fourth quarter were, in fact, NPM1 patients. Looking ahead, we will continue to expand our NPM1 business and are confident we will capture dominant market share and further cement our leadership position in menin inhibition. Our confidence is underpinned by our unmatched efficacy data, excellent customer relationships and a growing body of clinical data that differentiates Revuforj, including real-world evidence. The second driver is the robust transplant rate in KMT2A and growing use of Revuforj post-transplant. We estimate that approximately one-third of KMT2A patients treated with Revuforj have proceeded to a stem cell transplant with physicians putting their patients back on Revuforj after a three- to four-month pause for engraftment. And the latest claims data suggests that approximately 40% to 45% of these patients have now restarted Revuforj, and that's up from 35% to 40% reported last quarter. We expect this percentage will continue to increase as more patients complete the engraftment period and additional data is reported by leading institutions that are building experience with Revuforj in the post-transplant setting. Based on what we observed in our clinical trials and feedback from physicians, we expect patients could stay on therapy for one to two years post-transplant, given the high risk of relapse and the favorable tolerability of Revuforj. The third driver is continued use of Revuforj in early lines of treatment and growing use in combination with other therapies. Claims data show that approximately 70% of usage is in the second and third line among patients treated for active disease. This is important because when patients are treated earlier, you expect to see higher response rates, longer durations of response and a higher percentage of patients proceeding to transplant. Claims data also show about 40% of usage in combination with other therapies, and that's up from 33% in the third quarter. While Revuforj is approved and promoted as a monotherapy, the growing combination use highlights physicians' comfort with the Revuforj profile and could extend treatment durations. All these evolving treatment dynamics have an important impact on the average duration of therapy. In 2025, the first full year of the launch, the average treatment duration was in the four- to six-month range. As treatment patterns continue to mature in the second year of the launch, we expect this to extend to six to 12 months. We have everything we need to continue building a sustainable business with our first two indications for Revuforj, which together represents a $2 billion-plus market opportunity, as you can see on Slide 6. Turning to Niktimvo on Slide 7. The fourth quarter was another strong quarter for Niktimvo with $56 million in net revenue, up 22% from the prior quarter. 2025 net revenue reached $151.6 million, surpassing first year launch benchmarks set by REZUROCK. From the start of the launch through the end of the fourth quarter, approximately 13,500 infusions have been administered to more than 1,400 patients. We continue to receive excellent feedback from HCPs on the rapid and durable impact they are seeing with Niktimvo on fibrosis and inflammation across organ systems.

It's a pleasure to be on the call today to discuss the important milestones ahead and provide an update on our pipeline. We are focused on executing the programs that will demonstrate the full therapeutic potential of our medicines, starting with revumenib. We are advancing an integrated evidence generation plan to quickly deliver practice-changing data across the acute leukemia spectrum and lead global registration programs in newly diagnosed patients. Global enrollment is underway in our pivotal frontline trials of revumenib, and we aim to be the first to present pivotal data. Our frontline strategy is backed by compelling Phase I/II data indicating high rates of response, MRD negativity, and favorable tolerability with revumenib used in combination with varying intensities of chemotherapy. For patients ineligible for intensive chemotherapy, enrollment is underway in EVOLVE-2. This Phase III trial of revumenib, combined with venetoclax and azacitidine, targets newly diagnosed NPM1 or KMT2A patients. EVOLVE-2 has dual primary endpoints of complete remission and overall survival in the NPM1 population, supporting both accelerated and full approval pathways. For the fit NPM1 population, enrollment is also ongoing in REVEAL, the Phase III trial of revumenib with intensive chemotherapy, which has dual primary endpoints of MRD-negative complete remission and event-free survival for potential approvals. In the fit KMT2A population, we are exploring a novel approach. Alongside gathering more data through intensive chemotherapy, we are advancing the RAVEN trial with clinicians leading menin research. This innovative Phase II trial will assess revumenib in combination with ven/aza for newly diagnosed KMT2A patients considered fit for intensive chemotherapy. This trial builds on positive activity seen with revumenib combined with venetoclax and a hypomethylating agent in KMT2A patients. RAVEN could transform the standard of care for fit KMT2A patients if the efficacy outcomes are comparable or better than those typically seen with intensive chemotherapy combinations, but with less toxicity. Another point I want to make is that 2026 will be a year where Syndax showcases strong presence and scientific leadership at major medical meetings in our field. We anticipate reporting additional data from ongoing Phase Ib/II trials of revumenib combinations in frontline settings, including updates from the BEAT AML trial later in the year. We also look forward to sharing more data on revumenib's clinical use in the post-transplant maintenance setting, an area receiving growing scientific attention, along with further real-world evidence from leading institutions in the United States. At last year's ASH, we began to see the initial data from centers investigating outcomes with revumenib in a post-transplant maintenance setting. Investigators from MD Anderson presented real-world data from 10 pediatric patients with KMT2A or NUP98r acute leukemia who received revumenib as maintenance post-stem cell transplant, reporting that revumenib was well tolerated with promising early efficacy. At a median follow-up of 19 months, all patients were alive, and 90% were relapse-free. Likewise, at ASH, City of Hope investigators introduced the design of a Phase I trial evaluating the safety and preliminary efficacy of revumenib as maintenance for two years post-transplant in both adult and pediatric patients with NPM1 or KMT2A acute leukemia. This trial and others will yield significant data to guide future research and clinical practices. With over a year of commercial use, we and our collaborators are well positioned to deliver impactful real-world evidence supporting the clinical use of revumenib. Investigators at Moffitt Cancer Center shared the first real-world evidence for revumenib and the menin therapeutic class at ASH, showing an overall response rate of 77% and an MRD negativity rate of 75% among patients with relapsed/refractory NPM1, KMT2A, NUP98r acute leukemia who were primarily treated with revumenib as part of combination therapy. This underscores the clinical benefit of having a therapy effective across multiple genetic subtypes, distinguishing revumenib's profile and enhancing physician comfort in combining revumenib with standard therapies. They also reported on patients who transitioned to stem cell transplant, with most resuming revumenib post-transplant. We expect Moffitt to present more data this year, along with other centers that have extensive experience using revumenib in clinical practice. These important data sets will help further differentiate the application of revumenib and offer practice-informing insights to physicians.

Thank you, Nick. Earlier this afternoon, we reported detailed fourth quarter and full year 2025 financial results and I'll highlight just a few key points on Slide 14. Total revenue for 2025 was an impressive $172.4 million, consisting of $124.8 million in Revuforj net revenue, $42.4 million of Niktimvo collaboration revenue and $5.1 million in milestones and royalties. In the fourth quarter, Revuforj net revenue increased by 38% compared to the third quarter. This growth was driven by demand as inventory levels remained within the two- to three-week range we previously guided to. We expect continued growth over the coming quarters with the fourth quarter approval in NPM1 and an increasing average duration of therapy in KMT2A patients. Turning to Niktimvo. It was a meaningful cash flow contributor to Syndax in 2025. From the $151.6 million in 2025 Niktimvo net revenue reported by our partner, Syndax recorded $42.4 million in collaboration revenue after deducting the cost of sales and commercial expenses. We expect the Niktimvo margin contribution, defined as collaboration revenue recorded by Syndax as a percentage of Niktimvo net sales to be in the 25% to 30% range in the near term and increase longer term as sales grow while much of the expense base stays largely fixed. We expect continued robust sales growth given the high unmet need Niktimvo is addressing and the potential for patients to stay on therapy for extended durations. As previewed at the JPMorgan Conference in January, we expect 2026 expenses to be stable compared to 2025. We have guided to total R&D plus SG&A expenses in 2026 of approximately $400 million, excluding the impact of $50 million in estimated noncash stock compensation expense. And we expect expenses throughout the year to be relatively flat quarter-to-quarter. Turning to the balance sheet. We are well funded to continue investing in our commercial and development priorities with $394 million in cash, equivalents and marketable securities at the end of 2025. With a robust balance sheet, growing revenue from two medicines and stable expenses, we expect to reach profitability without the need for additional capital. With that, I will hand the call to Michael for closing remarks.

Thank you, Keith. 2025 was a landmark year for Syndax in which we solidified our scientific and commercial leadership. Looking ahead, we are laser-focused on driving revenue growth and delivering on the clinical milestones shown on Slide 15 that will fuel further innovation and value creation. We are in an excellent position to deliver on our commercial objectives with multiple drivers for near- and long-term growth of both medicines. Demand for Revuforj is accelerating as we expand into a second larger patient population and the number of patients on therapy post-transplant begins to stack. Revuforj is uniquely positioned to be the menin inhibitor of choice in the relapsed/refractory setting and the first menin inhibitor approved in the front line, unlocking a $5 billion-plus market opportunity. Niktimvo is annualizing at over $200 million and is a meaningful contributor to our bottom line within the first 11 months of launch. We have ample opportunity for further growth in our first indication and trials are underway in frontline chronic GVHD and IPF that could open transformational multibillion-dollar markets for Niktimvo. I will close by expressing my deep gratitude to the patients in our trials, our dedicated Syndax team, collaborators and long-term investors. Their unwavering support has made it possible for us to advance our mission to this point and continues to power Syndax's long-term success. And with that, I would like to open the call for questions. Operator?

Our first question will come from Anupam Rama with JPMorgan.

This is Priyanka on for Anupam. So last month at the JPMorgan Healthcare Conference, it was noted that usage in the KMT2A maintenance setting post-transplant was in the 30% to 40% range. Today, we're seeing about 40% to 45% having resumed treatment post-transplant. So what factors are driving the increase in such a short time?

Priyanka, thanks for the question. Look, the growth in KMT2A has been fantastic. And I think the post-transplant maintenance has been a big factor in the growth here. And we're talking about patients that are going to transplant right now at about one-third of patients going to transplant and then more patients continue to come back for maintenance. And so that is a growing phenomenon, and we've gone from 35% to 40% and now 40% to 45%. So it's continuing to step up quarter after quarter. And that's what we would expect. We would expect this to continue to grow, get us to even a higher watermark. This is something physicians want to do and believe in, and we're seeing the results quarter-over-quarter.

Your next question will come from Corinne Johnson with Goldman Sachs.

You mentioned that about 30% of patient starts are coming from NPM1 in terms of like the early data reads through this quarter. I guess, what do you think that should be at steady state? And then maybe separately, you obviously completed that enrollment in the IPF study. But could you remind us what you're looking for in order to determine a go-forward decision on that indication? And how does that decision get made between you and your partner Incyte?

Great. Thanks, Corinne, for the question. So maybe the first part, I'm going to make a comment and turn it over to Steve. Right about now 30% plus NPM1 as a percentage of new patient starts. We do expect that to grow. I mean we're off to a fantastic start. We have the best profile really anchored by efficacy and great tolerability. Physician awareness is high. So we're feeling that number will grow meaningfully throughout this year. And Steve, I don’t know if you make any other comments.

We've observed a progression regarding this matter. In previous quarters, the percentage aligned with the NCCN guidelines was much lower. In the third quarter, new patient starts were likely around 20%. Based on the data at hand, we estimate that figure at 30%, and we anticipate it will increase significantly. The NPM1 population is larger than that of KMT2A, so it will probably reach a 50-50 split fairly quickly. Ultimately, there will be more NPM1 patients due to a larger pool. To reiterate what Michael stated, we're excited about the beginning and the positive reactions we've seen in the fourth quarter. Although we haven't experienced a full quarter of promotion yet, we're noticing an increase in prescriptions from more accounts. As I noted in my earlier comments, formulary access is currently at 97%, similar to KMT2A, just a couple of months in. We're in a great position with a lot of momentum as we enter January.

Great. And Corinne, your second question related to IPF. I'm going to let Nick make some comments about what will essentially put us in a good position come the readout on IPF, Nick.

Yes. And first, I would just say it's a very well-designed and robust Phase II study. So it will give us a clear proof of concept that will inform. And we'll obviously look for both statistical significance, but also clinical relevance against historical controls. The primary endpoint of the study is forced vital capacity or FVC. In terms of absolute measures, just based on what we've seen from recent studies, something of the order of 40 mls difference at the 26-week primary endpoint annualized to about 80 to 100 ml when you analyze that out. Or if you benchmark it against Fibrnir, which showed across its two dose levels, a relative difference of about 23% to 38%, something in excess of 40% would be both statistically significant and clinically meaningful. But we are really looking for some sort of incremental change that would be extremely competitive versus currently approved standards of care. And based on all of the preclinical and clinical data that I went through in the prepared comments, we're feeling really quite confident in both the design and the outcome of this currently double-blind, placebo-controlled study that we hope to read out at the end of this year. So those are the sort of benchmarks we'll be looking for.

Yes. And lastly, I'd add that I think you had a question about our partner and how do we make the decision to go forward beyond the data. But I would just say that both us and our partner are eagerly awaiting the results of this trial, and we're in a great position to elect to go forward. And I expect that upon a positive result, both Syndax and Incyte will work together on the rest of the program, Phase III and launching that.

Your next question will come from Claire Dong with Jefferies.

So just kind of a follow-up question on the IPF trial. Let's say, if it reads out positively in the fourth quarter, can you talk about what's the fastest and realistic path to a pivotal trial and eventual approval? And then if the data is positive, how are you thinking about the next indication? And what criteria are you using to prioritize for the next indication?

Thanks for the question. I'll just make a comment and turn it over to Nick. Look, we would be as expeditious as possible in designing the next trial and executing on that. We haven't guided yet in terms of timelines for the next trial, but obviously, this would be a very important result for the franchise. And so we look to start a trial very quickly. Nick?

Yes. And just a few additional considerations. One is that we would be planning a Phase III with a subcutaneous regimen. We have a subcutaneous regimen of axatilimab in development. We feel that, that would be an important element of a future Phase III and approval. Based on the robustness of the Phase II design, we are only anticipating the need for one pivotal Phase III in IPF. We feel that would be sufficient to confirm what we see in proof of concept, assuming the study is positive. And obviously, our intent is to have Phase III enabled for as soon as we possibly can after the end of Phase II. So we are planning for success, all of the enabling work that we can do ahead of time we are doing whilst we await that signal. So we haven't guided, as Michael says, to the start of the Phase III, but those would be some considerations. The one other point I would make, of course, is that we'll have a very good statistical sense of the margin of benefit, which allows us to power Phase III appropriately, and I hope quite aggressively on the basis that we're really looking for a step change in clinical benefit.

Your next question will come from Josh Bowen with Guggenheim.

This is Josh on for Brad. So as you guys continue to capture patients earlier on in the disease course, you have more patients on combinations and more making maintenance, should we think about the overall contribution of each of those components to the trajectory towards that six to 12 months duration range you guys are noting for 2026?

Josh, thanks for the question. As you noted, combination use is growing. So we're seeing about 40% of our patients, and that's up from prior quarters, about 40% of our patients treated in combination, which is a great sign that we're treating them also earlier in the treatment regimen, which, of course, as was noted in, I think Nick's comments or Steve's comments, as you treat patients earlier, they tend to do better and stay on drug longer, and that's a recipe for success. Combinations allow that to be possible. So we do believe that, that number will grow over time. But of course, monotherapy is the basis of our approvals and how we're anticipating the drug will continue to be used as well. So a big part of our future. But as you approach frontline, that's really where combinations are going to become even more important. And we have, of course, the most data in the field around combinations at this point, and the drug has been very well tolerated and also showing great efficacy. So we're in a particularly good spot there.

Your next question will come from Phil Nadeau with TD Cowen.

Congrats on the progress. Two from us. So first, in terms of maintenance therapy, I think we're hearing at ASH that there was some question on the appropriate dose of Revuforj in maintenance. It seems like with use increasing, maybe those questions are subsiding. So are physicians comfortable with what dose they should be using in maintenance? And then second, on the strategy for moving Revuforj into newly diagnosed fit KMT2A patients, you talk about that a little bit more? It seems like you're betting on the Revuforj plus ven/aza trial. Is that a little risky in that intensive chemotherapy seems to be the standard of care today? So why not do a registration trial in combination with IC?

Yes, Phil, thanks for the question. First part of the question was related to maintenance therapy and our physicians now comfortable with the dose, given that maintenance use is increasing, I would say, yes. That's an easy one to answer. And I do think that we've done a lot in the field to look at real-world data and other publications in order to support the use of maintenance. And I think the specific dose has come up as a question, and we're trying to answer that, and we'll continue to answer that. Nick, you might want to comment on that.

Yes, No, thanks, Phil. And actually, we had a trial in progress, you may recall at ASH last year from Dr. Ball, City of Hope. We hope that data to read out this year. This is a Phase Ib/II study actually looking at optimizing the dose in the maintenance setting. It's dose escalating, we should be able to report that out. Currently, the standard dosing for maintenance is the same as our approved dose and indeed, it is the same dose that we take in combination with either ven/aza or intensive chemotherapy, which is the 160, 270 dose. Of course, physicians are allowed to dose modify as they need to, to manage any cytopenias in the maintenance setting. But I think that Phase Ib will be informative when it reads out in terms of the optimization of doses in maintenance. But that's where we stand with that. And then maybe I jump to fit KMT2A. Why don't you handle it.

So Phil, regarding RAVEN, we have the most extensive data set for KMT2A alongside both intensive chemotherapy and HMA regimens. This comprehensive data was the foundation for our front-line program, which encompasses all relevant areas. We have a randomized study planned in partnership with the NCI, which will involve intensive chemotherapy for KMT2A. We believe this collaboration is highly beneficial, building on their Phase I experience. As you know, we shared data from Phase I with the NCI at ASH, and that study will be advancing. Additionally, KMT2A patients are also included in our EVOLVE-2 study, where the primary endpoint focuses on NPM1, as NPM1 is the most significant population for unfit patients. However, KMT2A patients will be part of this study as well, and we will conduct a sensitivity analysis that considers KMT2A. Given the evolving clinical practices for fit KMT2A patients, we aim to innovate and believe we are well-positioned for this, collaborating with leading academic centers. There has been interest in combining ven/aza even for fit patients to lower morbidity, as we anticipate that these patients can reach transplant similarly to those undergoing intensive chemotherapy but potentially with less morbidity and toxicity associated with an intensive chemotherapy and menin combination. This innovative approach could advance the standard of care, and we are committed to continuing our efforts with thought leaders in this field.

Maybe just a follow-up. So could the NCI trial or EVOLVE-2 result in a label for first-line in combination with IC?

Yes. It's very much data dependent. I mean those could be practice informing, guideline informing or potentially label informing. It's going to depend on the outcome. It's going to depend a little on the patient population. So it will depend. We have, as I say, a broad program, including KMT2A, and it will depend on what we see.

Your next question will come from Stephen Wiley with Stifel.

I guess it looks like Niktimvo's sequential growth here in 4Q hasn't really slowed that much relative to 3Q, which seems to be a bit interesting for a second mover IV drug. So what anecdotes are you seeing? And are you thinking any differently about how long you might be able to see double-digit sequential growth for this franchise? And then I just have a follow-up.

Stephen, thank you for the question. Yes, we believe Niktimvo has had a fantastic first 11 months, surpassing expectations, and we anticipate continued growth this year. We feel optimistic about our quarter-over-quarter performance. Steve, do you want to add anything?

Yes. Great question, and the drug is off to a great start. I think the reason why it's serving unmet need that hits what hallmarks of the disease with fibrosis and inflammation, you've got an account base that there's not that many BMT centers in the country. Nearly all of them are writing and the effort that we have against it between Incyte and Syndax is pretty tight, but these are priority accounts and we support them, and we're seeing good dynamics, not just in new patients, but also in terms of persistency. So this is how these brands grow. There's a wide swath of patients at launch and then the goal is to bring in as many new patients as possible on a monthly basis, and we're consistently doing that. So it's going to feed itself and the product is going to perform as expected. We'll start to see durations increase. It's not uncommon for ultimately patients to be on for not months, but years. So those are the dynamics we'll see at play. So I would expect to see steady growth, if not increasing in the near future.

Yes, I think that really speaks to the overall growth profile, and we do think there's multiple dynamics in play here. And while we're very optimistic, I think, yes, reasonable expectations would lend to the notion that we should continue to see that sort of growth trajectory.

Your next question will come from Mayank Mamtani with B. Riley.

Congrats on the progress. Maybe I can stay on the IPF topic, if I may. So you are testing the lower dose here, at least relative to the 1 mg per kg GVHD trial. So maybe just comment on what you have seen in the dose response maybe from the AGAVE study before. And I also noticed you stratified by pirfenidone or nintedanib exposed patients. So how you expect to have sort of that powering between the two stratification? And is the Phase III trial also potentially going to be 26 weeks versus maybe the 52 weeks you usually see in IPF?

Yes. Go ahead, Nick.

So maybe start with the last one first. So a planned Phase III would have a standard FDA and other regulatory authority endpoint at 52 weeks. That would be the standard. So that's straightforward. We've annualized our Phase II, which is an accepted methodology, and we have a very robust statistical model for doing that. That's the first question. Your second question related to dose response, yes, this is actually very good because we had a very clear dose exploration in the AGAVE study where we explored three different doses and clearly showed that the lower dose 0.3 mg per kg was the most well tolerated, but also interestingly the most effective. And that applied equally in the patients that had bronchiolitis obliterans syndrome, which we've actually presented those data, where if you look at the 0.3 mg per kg, nearly 50% of the patients actually had a response using standard NIH criteria and 90% of those patients at the lowest dose had an improvement in their symptoms at rest, which is very encouraging. So we feel pretty confident that the dose that was approved for GVHD is the appropriate dose to be testing in IPF as well.

Your next question will come from Etzer Darout with Barclays.

Just quickly going back to an earlier comment. Just wondered what you're seeing regarding the most common combo agents being used currently? And then also exiting sort of the quarter, what average duration of therapy are you seeing? And how does it differ in NPM1 patients versus KMT2A patients?

Thank you for the question, Etzer. Regarding the combination agents, we are primarily seeing our product used in combination with venetoclax and azacitidine. We are also observing combinations with other agents, such as chemotherapy. However, for now, the majority of combination use is primarily with ven/aza. As for the average duration of therapy, we've previously mentioned that we expect it to be in the four- to six-month range for Rev in 2025, which aligns with our current expectations. While we won't comment on this year just yet, we are optimistic about what we are observing. We indicated that the duration could extend to six to twelve months, and we feel positive about that as well.

Your next question will come from David Dai with UBS.

Perhaps on the quarter. So we're a little bit encouraged to see the post-transplantation maintenance use increased to 40% to 45%. So what do you think would be a reasonable percentage at steady state? And then just on the IPF, axatilimab, how should we think about the competitive landscape, especially given that we have Tyvaso as well as Insmed, TPIP, both are inhalation? How do you think axatilimab could differentiate among the competitors?

Thank you for the question, David. Firstly, regarding the increase in post-transplant maintenance, it has risen to 40% to 45%, up from 35% to 40%. This is a great question about its potential future growth. We anticipate that this figure will substantially grow over the coming quarters, possibly reaching 70% to 80% of patients, based on physician insights indicating their intention to place all patients back on maintenance. However, we recognize that there will be certain circumstances preventing some patients from returning to maintenance. Overall, we believe that approximately 70% to 80% of patients could re-enter maintenance in this context, which represents a significant shift. No drugs have achieved this level of success, especially for KMT2A patients. NPM1 patients will have fewer transplants and, consequently, less maintenance as well. Nevertheless, this would mark a very significant change for these patients. Now, regarding IPF, Nick?

I believe it's important to highlight that idiopathic pulmonary fibrosis is an area with significant unmet medical needs. The current standards are not very effective, and we have hope that axatilimab may provide some level of disease modification by delaying early inflammation and possibly preventing or even reversing fibrosis. Evidence from wound healing suggests that there may be reversals in inflammation and fibrosis associated with certain skin changes. Most existing treatments mainly slow the decline in forced vital capacity to a limited extent. It's also worth noting that axatilimab has a unique mechanism of action, targeting macrophages, while most other treatments focus on fibroblasts, giving it a distinct profile. As we prepare for the Phase III trials, we plan to develop a subcutaneous treatment regimen that could be administered every two or four weeks, based on our findings. Other approved treatments can be cumbersome for patients, requiring inhalation of multiple puffs several times a day. Therefore, we believe a subcutaneous option administered less frequently could offer a competitive edge, especially if we have a positive outcome by the end of Phase II.

Your next question will come from Yigal Nochomovitz from Citigroup.

I just had a question on the real-world dynamics. So the combo use of 40% and the 70% second line or higher, are those percentages sort of steadily growing? Or do you see that as relatively stable for the time being until you generate evidence from those settings in the clinical trials?

Thanks, Yigal, for the question. I think it's very encouraging what we're seeing in the real world. We would expect the combo use of 40% to grow. Nick, do you want to comment on that?

Well, I would just say that we will be presenting some updates from the real-world data we presented at ASH at Moffitt through this year and also some further real-world series from other leading academic centers across the U.S. And what I can say is that the trend from those centers at least is that there is a desire to use it in combination because we've seen a higher response rate in CR/CRh. And for physicians and patients that can tolerate a combination, there is a desire to give them a combination because of those increased response rates. And I think as we generate more data and we present more experience from the real world, that will drive increased use because of those better outcomes. And we've also established it's very tolerable to give in combination.

Okay. And just one follow-up. Is it fair to assume that those metrics, the 40% and 70% are roughly similar across KMT2A and NPM1 or are there any notable differences there?

In terms of combination, I think we're about the same. I think we would think they would be the same. 70%, it could be very high relative to how many patients go back on from transplant, yes, similar.

Your next question will come from Salim Syed with Mizuho.

A couple from us. Just one, I appreciate the commentary on the 30% of your new starts are NPM1. Could you help us just reconcile that from a share perspective? So if every 10 NPM1 patients coming into the funnel eligible for menin, how many are you getting versus current right? Do you have any sense or any idea of what your share is there? And then just on the additional data that we'll be getting this year kind of related to Yigal's question, could you help us quantify what you think the halo effect might be in terms of uptake once you present that data for revumenib?

Great. So maybe the first question, I'll turn to Steve about the market share dynamics.

Yes, Salim, thanks for the question. This is things we'll look at over time. It's going to take us a little bit of time to parse that out. So it's just too early to know. I mean our data points are the same ones you have, which is what they provided as sales volume last year, which we know was on the low side. Some of that's by stocking. Some of that presumably is demand, but it's very small. I mean that we do know. Physicians have a choice, and we know that they're going to pick Revuforj based on the profile, the dynamics, the experience, formulary access and use they've had in this NPM1 patient population. So our focus is on broadening the patient population for Revuforj to the biggest number of patients as possible regardless of a competitor or not.

And your second question, Salim, just maybe restate it, if you don't mind.

Yes, sure. Just kind of related to Yigal's question. Just when we got this additional data that you plan on presenting for Revuforj this year and some of the combination data, just sort of how you're quantifying the halo effect you can see commercially in terms of uptake?

We are actively pursuing numerous collaborations. We've mentioned Beat AML and SAVE, along with several real-world evidence trials involving different patient groups. The way we use the drug, including maintenance, is crucial for its utilization, regardless of the specific indications. Our efforts will strengthen as we move into frontline treatment, and we're enrolling significant frontline trials. We expect to be among the first in this area and will have supporting data that could lead to potential guidelines before we even reach frontline treatment. Our strategy is strong, and as you noted, we should benefit commercially as we position ourselves as leaders in this field.

Your final question will come from Jason Zemansky with Bank of America.

Congratulations on the quarter. I have two quick follow-ups. Regarding your growth in NPM1 patients, do you have an idea of how much of that growth is due to an influx of patients before the approval? Additionally, since your competitor has only been on the market for a few months, can you provide any qualitative insights on whether their presence has affected your prescribing practices?

Yes. Jason, thanks for the questions. So maybe I'll let Steve address this question about growth in NPM1, kind of where we started and where we've kind of found ourselves. And then I'll come back to your competitor question in the end.

Yes, Jason. So in terms of bolus of patients, which you can see at launches of drugs, we certainly saw it at the launch of initially with KMT2A, there's this broad selection of patients that are on market that are available. And I think the best analogy I have for Revuforj, if you can consider KMT2A and the launch of the drug, it's a car to stop light, light turns green, you go with NPM1, it's a little different. You're kind of on an on-ramp getting on a highway and you're accelerating. So there's not going to be as pronounced of an effect on NPM1, meaning we've already captured some patients, and we know that an elevation of 10% in prior quarters of NPM1 use within Revuforj that accelerated in Q3 up to probably around 20%, and we're at least at 30%. So that's the ramp. I will say this, the number of new patients, we were pleased with what we saw. We continue to see that momentum roll into the first quarter of '26. So I feel like we're in a good spot.

Yes. I would like to mention that regarding competition, we believe we are in an excellent position. As Steve mentioned, we are in a fantastic place. We haven't experienced much impact. Our fourth quarter performance compared to our competitor's sales was strong. Therefore, we honestly expect to lead in this market. We have a superior product profile, and I anticipate that our execution will also be excellent. As we move into the year, we are very enthusiastic about what we can accomplish, and we feel we are in a great position.

This concludes our question-and-answer session. I will now turn the floor over to Mr. Michael Metzger for any additional comments or closing remarks.

Well, thank you all, and we appreciate everyone tuning in today to discuss our recent progress and the exciting milestones ahead. We look forward to seeing many of you at the upcoming conferences, TD Cowen, Jefferies, Leerink and Barclays. And so with that, have a great evening, everyone, and thanks for tuning in.