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 5 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 in full year 2025 financial and operating results with 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 Goldin chief financial officer this come 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 was discussed in the risk factor 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 Syndex.

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 positioned 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 men and inhibition. 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 relapsed refractory MPM1 mutated AML following the FDA's approval of our expanded label at the end of October. Our launch into MPM1 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 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 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 Resorock, 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 Revuforge, we were also the first company to initiate enrollment in a pivotal frontline trial of Amendant 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 axotilumab 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 axotilumab's utility in IPF and provide further rationale for its mechanism in a disease, 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.

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 ReviForge 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 a 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 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 RevuForge 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 Revenue Forge to their MPM-1 patients and positions us to drive further penetration in both MPM-1 and KMT-2A. Turning to slide 5, there are multiple factors that will drive continued Revenue Forge growth in the near term. The first driver is growing uptake of RevuForge in 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 MPM1 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 MPM1 and the results they've seen with RevuForge 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 NPM1, we began to meaningfully add new NPM1 patients following the addition of RevuForge 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 MPM-1 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 and 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 RevuMet of post-transplant. We estimate that approximately one-third of KMT2A patients treated with Rebuforge have proceeded to a stem cell transplant, with physicians putting their patients back in Rebuforge after a three- to four-month pause for engraftment. Now, the latest claims data suggests that approximately 40 to 45 percent of these patients have now restarted Rebuforge, and that's up from 35 to 40 percent before the 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 that's up from 33 percent in the third quarter while reviforge is approved and promoted as a monotherapy the growing combination use highlights physicians 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 twelve months we have everything we need to continue building a sustainable business with our first two indications for Revenue Forge which together represents a two billion dollar 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 Nick Timbo, 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 Resorok. 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 Nictimbo 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 GBHD market. While this is excellent progress, we still have significant room to continue growing and bringing the benefits of Nictimbo 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 percent of patients who started Nictimbo 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 NIC-TIMBO has strong commercial synergies for both Syndex and Insight. 90% of bone marrow transplant centers in the U.S. have prescribed NIC-TIMBO, with all centers placing repeat orders year-to-date. With multiple drivers for further growth, we are well positioned to expand our impact in Third Line Plus Chronic GVHD, a $2 billion U.S. market opportunity as shown on slide 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 Nick Timbo. 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 revenue many 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 review minute and we are positioned to be first to the frontline with pivotal data importantly our frontline strategy is supported by compelling phase 1 2 data showing high rates of response MRD negativity and favorable tolerability with RevuMenib 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 RevuMenib in combination with Venatoclax and Azacytid or venasa in newly diagnosed NPM1 or KMT to rate patients Evolve 2 has it 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 the phase 3 trial of Rebumenib 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 KNT2A 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 regimenate in combination with venasa in newly diagnosed KMT2A patients who would be considered fit for intensive chemotherapy. This trial builds on the strong activity observed with regimenate 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 ready-made 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 revument 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 sensors looking at outcomes with ReviMeneb 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 ReviMeneb as maintenance after their stem cell transplant. They reported that ReviMeneb was well-tolerated with encouraging early efficacy. At a median follow-up of 19 months, all the patients were relived, and 90% were relapse-free. Also at ASH, investigators from the City of Hoa presented the design of a Phase I trial evaluating the safety and preliminary efficacy of Rebiumenib 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 rebumenib clinical use investigators from moffat cancer center presented the first real-world evidence for rebumenib and the men in therapeutic class at ash their data showed an overall response rate of 77 and MRD negativity rate of 75% among patients with relapsed refractory NPM1, KMT3L, NUP98, acute leukemia, who received primarily Revumeneb 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 Revumeneb's profile, as well as physician's comfort, combining Revumeneb with standard of care therapies. They also reported patients proceeding to stem cell transplant, and the majority resuming RevuMenib post-transplant. In addition to observing excellent clinical activity overall, RevuMenib 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 for physicians turning now to axotilumab I'll highlight two key points first in partnership with insight we are working to expand axotilumab's impact in chronic GVHD with two ongoing trials in newly diagnosed patients one of these trials is a phase 3 of axotilumab in combination with corticosteroids with top-line data expected in early 2028 The other is a Phase II trial of axotilumab 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 GDHD. 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 MaxPIRE 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. Axetilumab is an IgG4, a 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 axotilumab has the potential to provide a more pronounced impact on the fibrotic process than other therapies that target alternate pathways slide 12 outline is the multiple lines of evidence that support the potential for actually to about 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 reduction in lung fibrosis with CSF1R inhibition. Most notably, we observed remarkable antifibrotic activity with axotilumab 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 axotilumab at the dose we are studying and ARP-IPF trial, nearly 50% achieved a lung response, and over 90% reported improvements and shortness 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 axotillomab's mechanism the compelling results in chronic gva gbhd and its potential in ipf site 13 shows the design of the maxpire a phase 2 randomized double blind placebo-controlled trial of axotillomab 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 force vital capacity or FEC measured at 26 weeks this is a well designed phase 2 trial that has the potential to provide robust proof of concept data axitl and I've been IPF to inform a pivotal registration program we 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. 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 fortunate revenue, $42.4 million of Indictimbo collaboration revenue, and $5.1 million in milestones and royalties. In the fourth quarter, revenue fortunate 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 the timbo it was a meaningful cash flow contributed to syndax in 2025 from the 151.6 million dollars in 2025 nick tempo net revenue reported by our partner syndex recorded 42.4 million dollars in collaboration in collaboration revenue after deducting the cost of sales and commercial expenses we expect the nick timbo margin contribution defined as collaboration revenue recorded by syndex as a percentage of nick timbo net sales to be in the 25 to 30 percent 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 big timbo is addressing and the potential for patients to stand therapy for extended durations as previewed of the jp morgan 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 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 review forage is uniquely positioned to be the men and inhibitor of choice in the relapse refractory setting and the first men and inhibitor approved in the frontline unlocking a five billion dollar plus market opportunity nick timbo is an annualizing at over 200 million dollars 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 be could open transformational multi-billion dollar markets for nick timbo 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 at this 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 JPMorgan. Your line is now open. Please go ahead.

Hey guys, this is Priyanka on for Anupam. The last month of the JPMorgan Health Care Conference, it was noted that usage in the KMT-2A 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?

Hi, Priyanka. Thanks for the question. Look, the growth in KMT-2A 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 Golden Sacks. Good afternoon.

Sorry, thanks. You mentioned 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 for a forward decision on that indication? And how does that decision get made between you and your partner, and I think?

Thanks, Corinne, for the question. So maybe the first part, I'm going to make a comment and turn it over to Steve. You know, 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 the 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 patient starts, Corinne. 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 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 reiterated what Michael said, we love to 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. Formulary access is, as I mentioned on my prepared comments, at 97%. That's just a couple of, you know, quarters, you know, a couple of months in. It's the same as it is on KT2A, so in a great spot, a lot of momentum at the end of the year carrying over into January.

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, no, thank you, Corinne. And firstly, 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, you know, we'll obviously look for both statistical significance, but also clinical relevance against historical controls. The primary endpoint of the study is force 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 Fibronia, which showed across its two-dose levels of 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 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, you know, currently double-blind placebo control study that we hope to read at the end of this year. So those are the sort of benchmarks we'll be looking for.

Yeah, and lastly, 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 see if it results 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?

All right, 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, you know, 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've looked to start a trial very quickly in it yeah and just a few additional considerations you know one is that we would be planning a phase 3 with a sub-q regimen we have a sub-q regimen of axitlimab in development we feel that would be an important element of a future phase 3 and approval based on the robustness of the phase 2 design we're only anticipating the need for one pivotal phase 3 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 be 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 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 through the trajectory towards that 6- to 12-month 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 and allow that to be possible so we do believe that that number will grow over time but of course monotherapy is is the basis of our approvals and 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 most the most data in 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 PD Callen.

Good afternoon. Congrats on the progress. Thanks for taking our questions. Two from us. 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 the 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 Venase 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 the 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 a specific dose has come up as a question, and we're trying to answer that, and we'll continue to answer that. And, Nick, you might want to comment on that.

Yeah, no, thanks, Phil. And actually, we had a trial in progress numerical at ASH last year from Dr. Ball, City of Hope. And we hope that day did 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 Ben A's 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 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 we I would say that we have by far the broadest data set with KMT2A in combination of both intensive chemotherapy and then HMA regimens and it was really the basis of the compelling nature of those data that we 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 I experience. As you know, we reported data from Phase I with the NCI at ASH, so that will be happening. We recall, of course, that KMT2A patients are included also in our Evolve 2 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 Venasa 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 plus men in combination so that is a 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 or evolve to result in a label for first line incumeration with IC?

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, Matt. Thanks for taking the questions. I guess it looks like McTinbo'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 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 point?

Yeah, great question, and the drug's off to a great start. I think, you know, the reason why it's serving on met need, it hits what, you know, 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 at play. 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 Actimbo and Boss chronic graft-versus-host disease from agave. And I'm just wondering if you can talk a little bit about the biological similarities and dissimilarities between that indication and IPF. Is one more vibrotic, is one more inflammatory than the other? and just try to think about how that data set should bode for translation at the IPF.

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

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 exotillumab cause really quite remarkable reductions in inflammatory cytokines like TNF, TGF-beta, IL-10, et cetera, which is also very encouraging. Interestingly, there are some recent publications, Blood 225, for some of the currently approved drugs in IPF that have shown activity in GDHD 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 pre-clinically and clinically with axitlimab will translate very well into IPF.

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

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 one week per gig GVSD 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 stratify by profanadone or nintedineb exposed patients so how you know you expect to have sort of that you know powering between the two stratification and and and is the phase three trial also you know potentially going to be 26 weeks versus maybe the 52 weeks you usually see in ips yes go ahead there so maybe start with the last one first so a planned phase three would have a standard fda another regulatory authority endpoint at 52 weeks that would be the standard so that's that straightforward we've 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 this your second question related to those response for 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 interesting and the most effective, and that applied equally in the patients that had bronchiolitis obliteran 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 GDHD is the appropriate dose to be testing in IPF as well.

Your next question will come from Esther DeRoot with Barclays.

Great. Thanks for taking the question. Just quickly going back to earlier, Tom, And 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 KMT2A patients?

Yeah, thanks for the question. So first, the combination agent, I think we're being used in combination with Ben-Aza probably most often. We're seeing it with other combination agents as well. 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 Ben-Aza. 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? Not good question.

Thank you.

Your next question will come from David Day with UBS.

Great, thanks for taking my questions and congrats from the quarter. So we're a little bit encouraged to see the post-transplantation maintenance use increase to 40 to 45 percent. So what do you think would be a reasonable percentage at steady state? And then just on the IPF, you know, acetylumab, how should we think about competitive landscape, especially given that we have tibasal as well as INSMEDs, TPIP, both are inhalations. How do you think, you know, an acetylmorphic could differentiate among the competitors?

Thanks, David, for the question. So, first, in terms of increase the movement and increased post-transplant maintenance, now at 40 to 45 percent, up from 35 to 40 percent. 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 it 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 change. Nothing's ever been able to, no drugs have been able to accomplish that, certainly for KMT2A patients.

NPM1 patients will will receive less fewer transplants and of course it would in turn less maintenance as well but but overall that's a that's a 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 higher met need You know the benchmark is not very high and we have you know Optimism that actually 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 um you know it we have to recognize as well actually film up has a very unique mechanism of action it's really targeting the macrophages as we about most of the other agents are targeting fibroblasts so that 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 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 Miguel Nachomovic 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, Yagal, 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, Yagal, 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 U.S. 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 higher response rate in CLCRH 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 you know more data and we present more experience from the real world that will will drive increased use because of those better outcomes. And we've also established it's very tolerable to given 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 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. 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 or NPM1. Could you help us just reconcile that from a shared perspective? So, if every 10 NPM1 patients coming into the funnel, you know, eligible for amenin, How many are you getting versus cura or reina? 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 thanks for the question. You know, these are 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 had, you know, 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, 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 the academies 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, just sure. It's kind of related to Yagal's question. And just when we get this additional data that you plan on presenting for RevuForge this year and, you know, 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. I mean, look, we're continuing to pursue lots of collaborations. We have – we talked about BDML. 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, you know, utilization, whether we have indications there or not. And that will build as we get to the front line. We're enrolling, you know, very significant front line trials. We expect to be first to front line, and we'll have all the data supporting that with potential for guidelines even before we get to front line. 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 Zemansky with Bank of America.

Good afternoon. Congrats on the quarter, and thanks so much for squeezing me in. Just a quick, 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, you know, 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?

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 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, you know, 10% in prior quarters of NPM1 use within Revue Forge, that accelerated in Q3 up to probably around 20, and we're at least at 30. So that's the ramp. You know, 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 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. I look forward to seeing many of you at the upcoming conferences, T.D. Cowan, Jeffries, Lyrinc, and Barclays. And so with that, have a great evening, everyone, and thanks for tuning in.