Syndax Pharmaceuticals, Inc.

Good day, everyone, and welcome to the Syndax fourth quarter 2025 earnings conference call. Today's call is being recorded. If you would like to ask a question following the company's prepared remarks, please press star five during the call. At this time, I would like to turn the call over to Sharon Clary, 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 Clary, 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 Kloster, 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 two. 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 may 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 three. I'm pleased to share our fourth quarter and full year financial results following a transformational year that positions Syndex 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 Syndex, and we have only just started to unlock the potential of our first two medicines. Let's dive into our commercial results for Revuforge. In the first full year of sales, we generated robust top-line results, delivering $125 million in Revuforge net revenue in 2025 and further solidifying our leadership in Mennon Innovation. Notably, we ended the fourth quarter with 38% growth in Reviforge 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 and relapse refractory NPM1 mutated AML following the FDA's approval of our expanded label at the end of October. Our launch into NPM One 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 ReviForge. We are confident we will win in NPM One 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 Nictimbo and chronic graft-versus-host disease, or GVHD. Fourth quarter results were strong, with a 22% increase in Nictimbo 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. Nictimbo 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 Resuroc, which reached $500 million in annual U.S. net sales within the first four years of launch in the same indication. Nictimbo's outperformance highlights its unique ability to address both fibrosis and inflammation. As we expected, Nictimbo contributed significantly to our bottom line in 2025. Our 50% share of the Nictimbo product contribution totaled $42 million in collaboration revenue to Syndax in 2025. As Nictimbo sales continue to ramp, while much of the expense base stayed largely fixed, we expect to retain an even larger proportion of Nictimbo revenue over time. Altogether, Syndex 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 lifecycle 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 Reviforge, we were also the first company to initiate enrollment in a pivotal frontline trial of a Menden inhibitor, positioning Syndax to be the first to frontline. We also delivered the first real-world evidence for a Menden inhibitor, among many other achievements that advanced our scientific leadership and the body of evidence supporting our medicines. More recently, we completed enrollment in MaxPyre, a robust phase 2 trial of axotilamab 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 axotilamab'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 Syndex 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 four. Now, as Michael noted, we reported strong results from our launch of Revuforge. In the first full year of the launch, we delivered $124.8 million in Revuforge 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 a 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 Revuforge accelerated throughout the quarter, resulting in $44.2 million in Revuforge net revenue, up 38% from the prior quarter. New patient starts were up about 20%, driven primarily by uptake in MPM1, bringing us to approximately 1,050 patients treated commercially since launch. With the vast majority being KMT2A patients, we approached 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 MPM1 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 RevenueForge 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 Reaviforge to their MPM1 patients and positions us to drive further penetration in both MPM1 and KMT2A. Turning to slide five. There are multiple factors that will drive continued Revuforge growth in the near term. The first driver is growing uptake of Revuforge and relapsed refractory MPM1 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 Reviforge 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 timelines. Regarding our ramp in MPM1, we began to meaningfully add new MPM1 patients following the addition of Revuforge to the NCCN guidelines for relapsed refractory MPM1 mutated AML towards the end of September. The latest available data suggests we exited the third quarter with MPM1 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 MPM-1 patients. Looking ahead, we will continue to expand our MPM-1 business and are confident we will capture dominant market share and further cement our leadership position in men in inhibition. Our confidence is underpinned by our unmatched efficacy data. excellent customer relationships, and a growing body of clinical data that differentiates Revuforge, including real-world evidence. The second driver is the robust transplant rate in KMT2A and growing use of Revumenta post-transplant. We estimate that approximately one-third of KMT2A patients treated with Revuforge have proceeded to a stem cell transplant, with physicians putting their patients back in Revuforge after a three- to four-month pause for engraftment. The latest claims data suggests that approximately 40% to 45% of these patients have now restarted Reviforge, 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 Reviforge 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 Reviforge. The third driver is continued use of Revuforge 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 and that's up from 33% in the third quarter. While Reviforge is approved and promoted as a monotherapy, the growing combination use highlights physician's comfort with the Reviforge 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 Revuforge, which together represent a $2 billion plus market opportunity, as you can see on slide six. Turning to Nick Timbo on slide seven. The fourth quarter was another strong quarter for Nictinvo, 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 Resiroc. From the start of the launch to 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're seeing with nictimbo on fibrosis and inflammation across organ systems. Turning to slide eight. There are multiple drivers for continued Nictinvo growth in 2026. First, continued adoption in the fourth line and growing usage in the third line. In the first 11 months of the launch, we estimate that we captured approximately 20% of the third line plus chronic GVHD market. While this is excellent progress, we still have significant room to continue growing and bringing the benefits of Nictinvo to more patients. Second, this is a chronic disease with the potential for patients to stay on therapy for long durations. Persistency rates are high with approximately 60 to 70% of patients who started Nictinvo in the first quarter of 2025 remaining on therapy at month 10. Our clinical trial experience shows that the duration of therapy can be measured in years for a meaningful proportion of patients. Third, we have a robust prescriber base, and Nictinvo has strong commercial synergies for both Syndex and Insight. 90% of bone marrow transplant centers in the U.S. have prescribed Nictinvo, with all centers placing repeat orders year-to-date. With multiple drivers for further growth, we are well-positioned to expand our impact in ThirdLine Plus Chronic GVHD, a $2 billion U.S. market opportunity, as shown on slide 9. In summary, we've made tremendous progress in our first year as a commercial company. We successfully delivered two novel medicines to thousands of patients and advanced the company towards profitability in the process. This is just the start of the impact we can make for patients with Revuforge and Nictinvo. With that, I'll hand the call over to Nick to talk about our pipeline.

It's a pleasure to be on the call today to discuss the important milestones ahead and update on our pipeline. So if you turn to slide number 10, we're laser focused on executing the programs that will characterize the full therapeutic potential of our medicines, starting with revumenib. We are advancing an integrated evidence generation plan to rapidly deliver practice-changing data across the acute leukemia spectrum, as well as leading global registration programs in the newly diagnosed setting. Some of the key trials are shown on this slide, and I would like to highlight a few key points. First, global enrollment is underway in our pivotal frontline trials of Revumenib, and we are positioned to be first to the frontline with pivotal data. Importantly, our frontline strategy is supported by compelling Phase I-II data showing high rates of response, MRD negativity, and favorable tolerability with Revimenib in combination with low or high-intensity chemotherapy regimens. Among the patients who are eligible or unfit for intensive chemotherapy, enrollment is underway in EVOLVE-2. This is a phase 3 trial of revimenib in combination with venadoclax and azacytidine or venaza in newly diagnosed NPM1 or KMT2A patients. EVOLVE-2 has dual primary endpoints of complete remission and overall survival based on the NPM1 population to support the potential for accelerated and full approval respectively. In the fit NPM1 population, enrollment is underway in Reveal, a phase 3 trial of Revimenib in combination with intensive chemotherapy. Reveal has dual primary endpoints of MRD-CR and event-free survival to support the potential for accelerated approval and full approval, respectively. In the fit KMT2A population, we are pursuing a novel approach. In addition to generating further data with intensive chemotherapy, we are progressing the RAVEN trial in collaboration with clinicians at the forefront of men in clinical research. This innovative phase 2 trial will evaluate revumeneb in combination with veneza in newly diagnosed KMT2A patients who would be considered fit for intensive chemotherapy. This trial builds on the strong activity observed with revumenib in combination with venatoclax and a hypermethylating agent in KMT2A patients. RAVEN has the potential to advance the standard of care for fit KMT2A patients if the efficacy outcomes are similar or superior to what is typically seen with intensive chemotherapy combinations, but without the associated toxicity. The second point I'll highlight is that 2026 will be another year in which Syndax will demonstrate a strong presence and scientific leadership at every major medical meeting in our field. Specifically, we expect to report additional data from the ongoing Phase 1b2 trials of revimented combinations in the frontline setting, including an update from the BEAT AML trial in the second half of the year. We also look forward to additional data presentations on the clinical use of Revimenib in the post-transplant maintenance setting, an area of growing scientific interest, as well as further real-world evidence collaborating with leading institutions across the United States. At last year's ASH, we saw the first of what we expect will be a growing body of data from centers looking at outcomes with revimenib 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 revimenib as maintenance after their stem cell transplant. They reported that Revumenib was well-tolerated with encouraging early efficacy. At a median follow-up of 19 months, all the patients were alive and 90% were relapse-free. Also at ASH, investigators from the City of Hope presented the design of a Phase I trial evaluating the safety and preliminary efficacy of Revumenib given as maintenance for two years post-transplant in adult and pediatric patients with NPM1 or KMT2A acute leukemia. This trial and others will provide important data to inform future research and clinical practice. With over a year of commercial use, we and our collaborators are well positioned to deliver impactful real-world evidence supporting revumenib clinical use. Investigators from Moffitt Cancer Center presented the first real-world evidence for revumenib and the men and therapeutic class at ASHE. Their data showed an overall response rate of 77%, an MRD negativity rate of 75% among patients with relapsed refractory NPM1, KMT2L, NUP98 acute leukemia, who received primarily Revimenib as part of a combination therapy. This usage highlights the clinical value of having a therapy with activity across multiple genetic subtypes, a differentiating feature of Revimenib's profile, as well as physicians' comfort combining Revimenib with standard of care therapies. They also reported patients proceeding to stem cell transplant and the majority resuming Revimenib post-transplant. In addition to observing excellent clinical activity overall, Revimenib was well tolerated. We expect Moffitt to report further data this year, as well as other centers with extensive experience using revumenib in clinical practice. These will be important data sets that further help to differentiate the breadth of revumenib use and provide practice-informing data to physicians. Turning now to axotilumab, I'll highlight two key points. First, in partnership with Insight, we are working to expand axotilamab's impact in chronic GVHD with two ongoing trials in newly diagnosed patients. One of these trials is a phase 3 of axotilamab in combination with corticosteroids, with top-line data expected in early 2028. The other is a phase 2 trial of axotilamab in combination with ruxolitinib, with top-line data expected in early 2027. Second, we continue to make progress advancing the development of axotilumab beyond chronic GVHD. Earlier this year, we completed enrollment in our Phase II trial of axotilumab in idiopathic pulmonary fibrosis, or IPF, and are on track for top-line data in the fourth quarter of 2026. Given the high interest in our IPF program, I will review some of the key evidence supporting this program and outline the Phase II MaxPy trial design. So turning to slide 11, monocytes and monocyte-derived macrophages are a promising target in IPF. A growing body of evidence supports that circulating monocytes migrate to the lung and become profibrotic inflammatory alveolar macrophages, which drive the fibrotic process. Research has shown that these monocyte-derived profibrotic macrophages are CSF1-dependent. Axotilamab is an IgG4 monoclonal antibody which was specifically optimized for diseases with an inflammatory and fibrotic component. It blocks a specific extracellular domain on the CSF1 receptor on the surface of monocytes and macrophages, preventing their activation by CSF1 and interestingly IL34. This reduces the levels of circulating pro-fibrotic and pro-inflammatory monocytes and monocyte-derived macrophages and therefore inhibits the activity of pathogenic macrophages in tissues. By targeting these cells, axotilamab has the potential to provide a more pronounced impact on the fibrotic process than other therapies that target alternate pathways. Slide 12 outlines the multiple lines of evidence that support the potential for axotilamab in IPF. Firstly, it has been shown that higher monocyte levels are associated with shorter overall survival in IPF and other fibrotic diseases. In addition, preclinical bleomycin mouse models of IPF show a reduction in lung fibrosis with CSF1R inhibition. Most notably, we observed remarkable antifibrotic activity with axotilamab in chronic GVHD patients. Responses were observed across all organ studies, including organs with fibrotic manifestations of the disease, such as the lung and skin. Among patients with lung involvement who received axotilamab at the dose we are studying in ARP-IPF trial, nearly 50% achieved a lung response and over 90% reported improvements in chance of breath at rest. Leading experts in IPF, with whom we have consulted, including some who are also participating in the trial, are enthusiastic about axotilamab's mechanism, the compelling results in chronic GVA, GVHD, and its potential in IPF. Slide 13 shows the design of the MAXPIRE, a phase 2 randomized double-blind, placebo-controlled trial of axotilamab in approximately 135 patients with IPF. The inclusion criteria are similar to other recently reported IPF trials. The primary endpoint is the annualized rate of decline in forced vital capacity, or FVC, measured at 26 weeks. This is a well-designed Phase II trial that has the potential to provide robust proof-of-concept data for axotilamide in IPF to inform a pivotal registration program. We have an exciting year ahead as we continue to pioneer the broad development of Menin and CSF1R inhibition, two mechanisms that hold tremendous promise for patients. With that, I will hand the call to Keith to discuss the financials.

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 revenue fortune net revenue, $42.4 million of Inictimbo collaboration revenue, and $5.1 million in milestones and royalties. In the fourth quarter, revenue fortune 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 MPM1 and an increasing average duration of therapy in KMT2A patients. Turning to Nictinvo, it was a meaningful cash flow contributed to Syndax in 2025. From the $151.6 million in 2025 Nictimbo 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 Nictimbo margin contribution, defined as collaboration revenue recorded by Syndax as a percentage of Nictimbo net sales, to be in the 25% to 30% range in the near term An increased 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 Nick Timbo 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 non-cash 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 Revuforge is accelerating as we expand into a second, larger patient population and the number of patients on therapy post-transplant begins to stack. Revuforge is uniquely positioned to be the Mennon inhibitor of choice in the relapse refractory setting and the first Mennon inhibitor approved in the frontline, unlocking a $5 billion plus market opportunity. Nictimbo 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 multi-billion dollar markets for Nictimbo. I will close by expressing my deep gratitude to the patients in our trials, our dedicated Syndex 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 Syndex's long-term success. And with that, I would like to open the call for questions. Operator?

At this time, I would like to remind everyone, in order to ask a question, please press star, then the number five on your telephone keypad. If you would like to withdraw your question, press star and the number five once again. We'll pause just a moment to compile the Q&A roster. Our first question will come from Anupam Rama with J.P. Morgan. Your line is now open. Please go ahead.

Hey, guys. This is Priyanka on for Anupam. So last month at the J.P. Morgan Health Care 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? Thanks.

Hi, 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. We're talking about patients that are going to transplant right now. There are about a 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. Good afternoon.

Sorry, thanks. You mentioned that about 30% of patients 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, you know, go forward decision on that indication. And how does that decision get made between you and your partner in science? Thanks.

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

I mean, only thing to add is we've seen a progression of this. You know, we knew in previous quarters it was a much lower percentage. Again, CCN guidelines, you know, we talk about third quarter, which is probably closer to 20% new patients start to CRIN. So 30 is our best estimate based on the data we have. It is going to go up meaningfully. We know the NPM1 population is... is larger than the KMT2A population. So it'll likely pretty quickly go to 50-50. In the end, it's going to be more NPM1 patients simply because there's more out there. But reiterate what Michael said. We love the start. We love the reaction we've got in the fourth quarter. We haven't even had a full quarter yet of promotion. We're seeing more accounts prescribed. Formula access is As I mentioned on my prepared comments, at 97%. That's just a couple of months in. It's the same as it is on K-2-2-A. So in a great spot, a lot of momentum at the end of the year carrying over into 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.

Yeah, and firstly, I would just say it's a very well-designed and robust phase two study, so it will give us a clear proof of concept that will inform. And, you know, 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 mils difference at the 26-week primary endpoint annualized to about 80 to 100 mils when you analyze that out. Or if you benchmark it against Fibonir, which showed across its two dose levels a relative difference of about 23 to 38 percent, something in excess of 40 percent would be both statistically significant and clinically meaningful. But we are really looking for some sort of incremental change in 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.

Yeah, 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 Syndex and Insight will work together on the rest of the program phase three in launching that.

Your next question will come from Clara Dawn with Jefferies.

Hi, good afternoon. Thanks for taking my question. 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 and 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? Thank you.

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 would look to start a trial very quickly.

Yeah, and just a few additional considerations. One is that We would be planning a phase three with a sub-Q regimen. We have a sub-Q regimen of axotinamab in development. We feel that that would be an important element of a future phase three and approval. Based on the robustness of the phase two design, we're only anticipating the need for one pivotal phase three 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 three enabled for as soon as we possibly can after the end of phase two. 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 three, but those would be some considerations. The one other point I would make, of course, is that we'll have very good statistical sense of the potential. margin of benefit, which allows us to power phase three 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.

Hey, guys, 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 it to maintenance. Should we think about the overall contribution of each of those components to the trajectory towards that six to 12-month duration range you guys are noting for 2026? Thanks.

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 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 big part of our future. But as you approach frontline, that's really where combinations are 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 shown great efficacy. So we're in a particularly good spot there.

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

Good afternoon. Congrats on the progress. Thanks for taking our questions. Two from us. So first, in terms of maintenance therapy, I think we were hearing at ASH that there was some question on the appropriate dose of Rebiforge 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 Rebiforge into newly diagnosed fit KMT2A patients, could you talk about that a little bit more? It seems like you're betting on the Rebiforge plus Venizia 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? Thank you.

Yeah, Phil, thanks for the question. First part of the question was related to maintenance, therapy, and are physicians now comfortable with the dose given that maintenance use is increasing? I would say yes, right? 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.

Yeah, no, thanks, Phil. And actually, we had a trial and progress numerical at ASH last year from Dr. Ball, City of Hope. We hope that data to read out this year. This is a phase 1B2 study actually looking at the 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 is the same dose that we take in combination with either venase or intensive chemotherapy, which is the 16270 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 1B will be informative when it reads out in terms of the optimization of dose and maintenance. But that's where we stand with that. And then maybe jump to fit KMT2A. So, Phil, the thinking with Raven, and firstly, I would say that we have by far the broadest data set with KMT2A in combination with both intensive chemotherapy and van HMA regimens. And it was really the basis of the compelling nature of those data that we collected. set out our program in the front line that really includes all of the areas. So recall that we have a randomized study planned in collaboration with the NCI, which will be with intensive chemotherapy for the KMT2A. And we think that's a very valuable collaboration building on their phase one experience. As you know, we reported data from phase one with the NCI at ASH. So that will be happening. Recall, of course, that KMT2A patients are included also in our Evolve2 study. The primary endpoint is powered for NPM1 because, of course, for unfit patients, NPM1 is the predominant population, but KMT2A patients will be included. And we will be doing a sensitivity analysis that includes KMT2A. And then really based on the evolving or, you know, changing perhaps clinical practice for fit KMT2A, we really wanted to innovate and felt we were in a good position to do that working with leading academic centers. And there was some interest in combining with Veneza, even for fit patients to reduce morbidity, because we really believe you will be able to get those patients to transplant In the same way as you would with intensive chemotherapy, but perhaps without all of the associated morbidity and toxicity that you might get from an IC plus men in combination. So that is an innovative approach that we really feel could move the standard of care forwards. And that's what we're focused on. And we really want to continue to innovate with the thought leaders in this space.

Maybe just to follow up. So could the NCI trial evolve to result in a label for first line in combination with ICs?

Yeah, 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'll depend. We have, as I say, a broad program, including KMT2A. And, you know, it'll depend on what we see.

Your next question will come from Stephen Wiley with Stiefel.

Yeah, good afternoon. Thanks for taking the questions. I guess it looks like Nick Timbo'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, thanks for the question. Yeah, we agree. Nick Timbo is off to a, you know, he's had a great first 11 months succeeding benchmarks and we see continued growth into this year for sure. So we're feeling quite good about quarter over quarter. But Steve, do you want to make some comments?

Yeah, great question. And the drug's off to a great start. And I think the reason why it's serving unmet need, it 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 Insight 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 a place. So I would expect to see steady growth, if not increasing in the near future.

Okay. And then I know you and Insight made a presentation, I think it was at ATS last year, looking specifically at the tempo in BOSC, chronic graft-versus-host disease from agave. And just wondering if you can talk a little bit about the biological similarities and dissimilarities between that indication and IPF. Is one more fibrotic? Is one more inflammatory than the other? We're just trying to think about how that data set should bode for translation at the IPF.

Thanks. Yeah, excellent question. Thank you. Thank you, Steve. I'm going to turn it over to Nick.

Yeah, actually, there's a lot of underpinning similarities in terms of the biology. I mean, both are associated with both inflammation and fibrotic changes. Both of them are associated with increased numbers of circulating monocytes and macrophages. So whilst, as you rightly point out, GVHD pulmonary manifestations tend to be more obstructive in their pattern, You get a more restrictive pattern in IPF. We feel a high degree of confidence that what we saw in those bronchiolitis obliterans syndrome pulmonary manifestations of GVHD is quite a good analog for IPF. We've also seen axotilamab cause really quite remarkable reductions in inflammatory cytokines like TNF, TGF-beta, IL-10, etc., which is also very encouraging. Interestingly, There are some recent publications, blood 2025, for some of the currently approved drugs in IPF that have shown activity in GVHD as well. And that kind of cross-reference does suggest that there are some common underlying pathologies, which we believe is the case, that gives us a lot of confidence that what we've seen, both preclinically and clinically, with axotilamab will translate very well into IPF.

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

Yes, good afternoon, team. Thanks for taking your questions and congrats on the progress. Maybe I can stay on the IPF topic, if I may. So you were testing the lower dose here, at least relative to the 1 mcg 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 perfenadone or nintedineb. So how, you know, you expect to have sort of that, you know, powering between the two stratification and is a phase three trial also, you know, 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 three 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 two, 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. Oh, the dose response. Yes, sorry. Yes, this is actually very good because we had a very... We had a very clear, you know, dose exploration in the agave study where we explored three different doses and clearly showed that the lower dose, 0.3 mg per gig, 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 gig, 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 Esther DeRute with Barclays.

Great. Thanks for taking that question. Just quickly going back to an earlier comment, just wondered what you're seeing with regard to the most common combo agents being used currently and then also, you know, exiting sort of the quarter, what average duration of therapy are you seeing, and how does it differ in M1 patients versus KMP2A patients? Thank you.

Yeah, thanks for the question. So first, the combination agent, I think we're being used in combination with Veneza probably most often. We're seeing it with other combinations agents as well. Yeah, IC is another, obviously, with chemotherapy. But I think we'll start to see that expand as time goes on. But right now, I would say the majority of the combination uses is more often with Veneza. And then in terms of average duration of therapy, I think we talked about 2025, we'd be in the four to six month range for REB. And that's squarely where we were. So I think we're not going to comment on this year yet. We're in this quarter, but we're encouraged by what we're seeing. We said that would extend to six to 12 months. And we feel good about that as well. So I think that's the average duration of therapy. Was there a third question? Thank you.

Your next question will come from David Day with UBS.

Great. Thanks for taking my questions. So we're a little bit encouraged to see the post-transplantation maintenance use increase to 40% to 45%. So what do you think would be a reasonable percentage at steady state? And then just on the IPF, you know, exotelium map, how should we think about competitive landscape, especially given that we have Tyvesial as well as InSmartz, PPIP, both are inhalations. How do you think, you know, Hasilimab could differentiate among the competitors?

Thanks, David, for the question. So first, in terms of increased the movement and increased post-transplant maintenance, now at 40% to 45%, up from 35% to 40%. So that was last quarter. Look, I think this is a great question. Where could this go? We would expect this number to meaningfully increase over quarters. And so... could be 70, 80% of patients based on what physicians tell us. They want to put all their patients back on maintenance. However, we know that there are extenuating circumstances where some patients won't be able to go on maintenance, but we expect somewhere in the order of 70, 80% of patients could go back on maintenance in this setting. And that's obviously a steep change. Nothing's ever been able to, no drugs have been able to accomplish that Certainly for KMT2A patients, NPM1 patients will receive fewer transplants and, of course, in turn, less maintenance as well. But overall, that would be a very meaningful change for these patients. And then in terms of IPF, Nick?

Yeah, I mean, I think the first thing to say is that, I mean, IPF remains an area of high unmet need. You know, the benchmark is not very high and we have, you know, optimism that axotilamab may actually bring a degree of disease modification, delaying early inflammation, potentially preventing fibrosis, maybe even reversing fibrosis. We shall see. We have some evidence from certainly wound healing that there seems to be some reversal of both inflammation and some of the fibrosis you see in some of the sclerotic changes of the skin. So, you know, the bench is not very high. Most of the currently approved standards of care just delay the deterioration FEC to an extent. You know, we have to recognize as well, axotinamab has a very unique mechanism of action. It's really targeting the macrophages, as we talked about. Most of the other agents are targeting fibroblasts. So that brings a very differentiated profile. And then, as I mentioned, if we as we. plan and for the phase three, we would be planning for a sub-Q regimen. It would be Q2 or Q4, potentially based on the data we've generated. Some of the other currently approved agents are quite difficult to prescribe, you know, inhalation, sometimes four puffs three times a day. I mean, it's quite onerous for patients. So we think a sub-Q regimen, Q2 or Q4 could be really quite competitive in terms of its profile. So I think those are the things which would differentiate us at the end of phase two with a positive signal.

Your next question will come from from Citigroup.

Yeah. Hi. Thank you very much. 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. So, look, I think it's very encouraging what we're seeing in the real world. And I think the combo use 40%, we would expect that to grow. And then in terms of, Yigal, you want to make a comment on?

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 US. And, you know, 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 high response rate in CRCRH. And for physician 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 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, thanks.

And just one follow-up. Is it fair to assume that those metrics, the 40% and 70% are roughly similar across KMT2A and MPM1 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. And 70%, you know, 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.

Hey, guys. Thanks for the questions. 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, you know, eligible for a Mennon, how many are you getting versus Cura, right? Do you have any sense or any idea what your share is there? And then just... On the additional data that we'll be getting this year, kind of related to Yagal'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 every minute? Thank you.

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

Yeah. And sleep. Thanks for the question. You know, there's just 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 which we know is on the low side. Some of that's probably stocking. Some of that presumably is demand. But it's it's very small. I mean, that that we do know. physicians, you know, have a choice and, you know, we know that they're going to pick Reviforge based on the profile, the dynamics, the experience, formulary access, and use they've had in this NPM1 patient population. So, you know, our focus is on broadening the patient population from Reviforge 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.

Yeah, sure. It's kind of related to Yagal's question. When we get this additional data that you plan on presenting for RevuForge 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.

Very important. Look, we're continuing to pursue lots of collaborations. We talked about Beat AML. We talked about SAVE. We talked about several of these real-world evidence trials that we're generating with combinations, both in the fit and unfit settings. All of that, how we use the drug, maintenance, all of that is exceptionally important when it comes to utilization, whether we have indications there or not. And that will build as we get to the frontline. We're enrolling very significant frontline trials. We expect to be first to frontline. And we'll have all the data supporting that with potential for guidelines even before we get to frontline. So we have a very robust plan. And as you say, a halo, which should accrue to us as we are the leaders here in this space.

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

Good afternoon. Congrats on the quarter, and thanks so much for squeezing me in. Just two quick follow-ups, if I may, from me. In terms of your growth in NPM1 patients, can you or do you have a sense of how much of that represents a bolus of patients prior to the approval? And then, I guess, secondarily, given that your competitor has been on the market just for a few months, Can you at least qualitatively comment on whether or not you've seen an impact at all on your prescribing? Thanks.

Yeah, 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.

Yeah, Jason. So in terms of bolus of patients, which you can see at launches of drugs, you know, we certainly saw it at the launch of initially with KMT2A. There's this, you know, broad selection of patients that are on market that are available. And I think the best analogy I have for Revuforge, if you can consider KMT2A in the launch of the drug, it's a car to stoplight. 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 Revuforge, 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. And we continue to see that momentum roll into the first quarter of 26. So I feel like we're in a good spot.

Yeah, and I just add relative to competition. Look, we feel we have – we're in a – as Steve said, we're in a fantastic place. Can't say we felt much of an impact. You know, we've had a great – we had a great fourth quarter relative to our competitor, you know, what their sales were. So we expect – honestly, to dominate this space. We have a superior product profile, and I expect we'll have superior execution. So we're, again, going into the year with very strong enthusiasm around what we can achieve, and we're in a fantastic spot.

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. Look forward to seeing many of you at the upcoming conferences, TD Cowan, Jeffries, Lyrinc, and Barclays. And so with that, have a great evening, everyone. And thanks for tuning in.