Syndax Pharmaceuticals, Inc.

Good day, everyone, and welcome to the Syndax first quarter 2026 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 spell five during the call. At this time, I would like to turn the call over to Sharon Cleary, head of investor relations at Syndax Pharmaceuticals.

Thank you, Operator. Welcome, and thank you all for joining us today for a review of Syndox's first quarter 2026 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 factor section in the company's most recent quarterly report on Form 10Q, as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, April 30, 2026 only. A replay of this call will be available on the company's website, www.syndax.com, following its completion. And with that, I'm 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. In the first quarter, we continue to make strong progress advancing our commercial objectives and pipeline programs designed to unlock the full potential of our first two medicines. On the commercial front, we delivered over $100 million in combined sales of Revuforge and Nictimbo, underscoring robust demand for both medicines and advancing the company towards profitability. RevenueForge net revenue totaled $49 million in the first quarter, highlighting our leadership position in men in innovation and strong adoption across both indications. Revuforge net revenue grew by double digits quarter over quarter, primarily driven by new NPM1 patients. Adoption in NPM1 has been strong and growing steadily since Revuforge was added to the NCCN guidelines for relapse refractory NPM1 mutated AML in September of 2025, followed by the FDA approval of our expanded label in October of 2025. We are the leaders in the relapse refractory space in both NPM1 and KMT2A and well-positioned to drive further growth and unmatched efficacy data and expanding prescriber base, excellent payer coverage, and multiple evolving treatment dynamics that should ultimately extend the average duration of therapy, including a growing number of KMT2A patients proceeding to transplant after receiving Reviforge. Notably, recent analysis indicates that Reviforge is enabling nearly half of KMT2A patients to receive a potentially curative stem cell transplant, a significant increase from our prior estimates of 33%. This growing transplant rate gives patients the best chance for durable remissions, ultimately driving longer treatment durations as an increasing number of patients return to therapy post-transplant. This step change compared to the 25% transplant rate we observed in our clinical trial aligns with what we have expected as Reviforge is used earlier in the treatment paradigm and often in combination with other therapies in the real world. The pool of patients on Revuforge post-transplant is expanding each quarter, although that growth continues to be obscured by the large number going to transplant. While the robust transplant rate seen with Revuforge has a short-term impact on the business, it is first and foremost a very positive outcome for patients and will translate into durable and sustainable growth as an increasing number of patients return to therapy. This is an important and unique growth driver of our KMT2A business. Turning to Nictimbo and chronic graft-versus-host disease, or GVHD. Nictimbo delivered $55 million in net revenue in the first quarter. This result reflects consistent new patient starts, partially offset by natural attrition among the large cohort of predominantly later line patients who started Nictimbo during the first quarter of launch last year. Notably, the same dynamic was also seen during the same period of the launch of Resiroc, as well as other rare disease therapies. Looking ahead, we expect strong growth with multiple drivers supporting the business, including a broad prescriber base and increasing uptake in the third line, which should extend the average duration of therapy. Turning to our pipeline, we've made excellent progress advancing the programs that will fuel the next phase of growth for the company, including our pivotal frontline trials of Revimentib. We are well positioned to be the first to get a Mennon inhibitor approved in frontline AML with strong global site activation, and patient enrollment underway in our pivotal trials. We will continue to expand the body of evidence supporting our medicines with multiple important data readouts anticipated in the second quarter and throughout the year. Similar to past years, we will have a major presence at ASCO, EHA, and ASH with new data for multiple studies of Reviforge across the acute leukemia treatment continuum, including new maintenance data, which will be highlighted in an oral session at ASCO. These upcoming datasets will continue to advance our leadership in men and inhibition and highlight ReviForge's best-in-class profile across multiple acute leukemia subtypes and settings. We are also nearing two potentially transformative Nictimbo readouts in the fourth quarter, including phase two data in idiopathic pulmonary fibrosis, or IPF, and in newly diagnosed chronic GVHD patients treated with Nictimbo plus Jacify. Data from these trials could further unlock Nictimbo's multibillion-dollar potential in chronic GVHD, IPF, and beyond. From a position of strength, we are delivering long-term and sustainable growth and advancing innovative treatments that can significantly improve the lives of patients. We have a world-class R&D and commercial organization with a proven track record of delivering breakthrough medicines to patients. We have two products poised for future label expansion, important upcoming data readouts, and the expertise necessary to continue delivering innovative medicines. We are well-funded to invest in the successful commercialization and further development of RevenueForge and Nictimbo and on our way to reaching profitability with growing revenue and a stable expense outlook. I'll now turn the call over to Steve to discuss our commercial results in more detail.

Steve?

Thank you, Michael. Starting with RevenueForge on slide four. Reviforge is now a little over a year into launch and by any measure, it has been an exceptional commercial success with net revenue now annualizing at nearly $200 million. We continue to track well above launch benchmarks set by other AML therapies and expect to continue to outpace other drugs and redefine success in this space. Two factors underpin our conviction, our ability to target a substantially larger population, another mutation-directed AML therapies, and multiple treatment patterns that are expected to extend the average treatment rate. In the first quarter, we delivered approximately $49 million in revenue for net revenue and double-digit quarter-over-quarter growth across all key metrics, including net revenue, total prescriptions, and new patient starts. Two drivers of our business, new patient starts and patients returning to therapy post-transplant, and both are building nicely. We added about 330 new patients in the first quarter, up approximately 10% compared to last quarter, with the growth driven by new MPM-1 patients. New patient starts have increased even more significantly compared to the 200 to 250 patients we were adding per quarter prior to the expansion of the Revuforge label to include patients one year and older with relapsed refractory MPM1 mutated AML. We've continued to gain momentum and reach new highs, demonstrating the durability of Revuforge's strong market position, even with the launch of a second menin inhibitor approved for adult MPM1 patients. Early indicators suggest at least 40% of new starts in the first quarter were NPM1 patients, up significantly from 10% of new patients prior to the NCCN guideline update in September of 2025. Between the NPM1 patients who started in the first quarter and those continuing on therapy from prior months, we estimate NPM1 accounted for at least 30% of the $49 million in net revenue. We're positioned to be the market leader in MPM-1 with the strongest clinical profile. In recent market research, HCPs who treat our target population ranked efficacy as the most important factor in their treatment decision, followed by safety and tolerability, availability of long-term efficacy data, personal experience with the drug, and inclusion in clinical guidelines. Notably, more HCPs strongly favored Reviforge over the other approved Mennon inhibitor on the top five most important factors, as well as nearly all other factors, including ease of access, drug-to-drug interactions, peer or KOL endorsement, ease of administration, flexible dosing, to name a few. Turning to slide five. We have a strong foundation to support the continued expansion of our KMT2A and MPM1 business, including a world-class team with excellent customer relationships and favorable listings in the NC-SED guidelines, the most influential guidelines for clinicians as well as payers. Our already robust prescriber base has continued to expand following our approval in MPM-1, including our activation of Tier 1 and Tier 2 accounts, the highest volume centers in the U.S., who treat two-thirds of our target population. Over 85% of these accounts have now ordered, up from 70% prior to the label expansion. The total number of accounts that have ordered has also increased quarter over quarter and is now well over 500 accounts, reflecting growing adoption in centers of all sizes, including community practices. Our growing prescriber base reflects physicians' enthusiasm to use Revuforge for their MPM-1 patients and positions us to drive further penetration in both indications. We also have nearly perfect payer coverage, and physicians can access the med and inhibitor they prefer without any meaningful barriers. Reviforge's formulary coverage stands at 97% of all covered lives, including all commercially covered lives, Medicare, and Medicaid, a coverage position that leads the class. We have engaged and educated payers extensively, and they recognize the value of Revuforge and its status as the only menin inhibitor approved for multiple acute leukemia subtypes. While the class leader in NPM1 will be determined by HCP preference, not price or recommendations from payers, I will note that payers understand the two menin inhibitors are priced at parity, with Revuforge actually costing less for the large percentage of patients on CYP384 inhibitors. This was made clear in a recently updated IPD analytics monograph, which no longer suggests use of one minute inhibitor over another based on price alone, clearing up a point that had led to temporary confusion among a small handful of plans representing less than 1% of all covered lives. Turning to slide six and the multiple factors that will drive further Revuforge growth. The first is our continued expansion into relapsed refractory NPM1 mutated AML. Of the 4,500 patient annual incident population, we estimate that less than 10% of patients have received a Mennon inhibitor, highlighting the substantial opportunity for further growth. Compared to KMT2A, where we saw a steep uptake curve due to the lack of other approved therapies, we expect our NPM1 business will build over time because there are other options that physicians may consider for this population, depending on their commutations, for example. With two to two and a half times as many NPM1 patients as KMT2A patients, we expect NPM1 will become a major component of our business over time. With strong physician support and unmatched efficacy data in a disease where efficacy is the most important attribute to physicians, we expect to have dominant market share in NPM1 and KMT2A. The second factor is the growing number of KMT2A patients who are proceeding to transplant after receiving Revuforge and then returning to therapy post-transplant. As Michael noted, the transplant rate has been building over time, with recent analysis indicating that nearly half of KMT2A patients are proceeding to transplant after receiving Revuforge. Around 45% have restarted after pausing treatment for one to two quarters, a percentage we expect will grow over time. While the pool of patients in RevuForge post-transplant is expanding, that growth continues to be obscured by the large number going to transplant each quarter. Importantly, we expect to observe a meaningful step up in post-transplant use after leading institutions report on their experience using RevuMentiv as maintenance in the second quarter. Long-term, we expect up to 70% to 80% of transplanted patients will ultimately be put back on therapy for one to two years based on our clinical trial experience and feedback directly from physicians. The third factor is use of Reviforgen early lines of treatment and in combination with other therapies. Claims data show about 70% of use in the second and third line, even as we've added more NPM1 patients to our mix. This is encouraging because when patients are treated earlier, you expect to see higher response rates, longer durations of response, and more patients proceeding to transplant as we now see playing out. Claims data also show about 40% combination use. While Reviforge is approved and promoted as a monotherapy, the significant combination use highlights physician's comfort with the Reviforge profile, and that could extend treatment durations. All these evolving treatment patterns will drive an increase in the average treatment duration, especially the growing number of KMT2A patients proceeding to transplant and then returning to therapy. This group of patients is already approaching nine months of therapy on average, with this duration expected to meaningfully increase over time. We are confident in our ability to continue building a sustainable business with our first two indications for RevuForge, which together represent a $2 billion plus market opportunity as shown in slide seven. Turning to Nictimbo on slide eight. Building on an excellent launch year, Nictimbo delivered $55 million in net revenue in the first quarter of 2026, and is now annualizing at over $200 million. In the first quarter, about 5,000 infusions were administered and approximately 300 new patients started, even with severe weather impacting patient access to infusion drugs in the first quarter. Performance this quarter reflects strong and consistent new patient starts and solid persistency, partially offset by natural attrition among the large cohort of predominantly later line patients who started Nictinvo during the first quarter of last year. This dynamic was also seen at a similar point in the Resiroc launch, a drug which reached $500 million in annual US net sales within the first four years of launch in the same indication. All indicators of demand suggest we will resume growth next quarter as we continue to steadily add new, less advanced patients. Turning to slide nine. The fundamentals of our Nictinvo business remain strong with multiple drivers for continued growth. The first is continued adoption in the fourth line and growing usage in the third line. Within one year of launch, Nictinvo has captured 32% of the third-line plus market with the majority of use in the fourth line and increasing uptake in the third line as providers gain experience. As the patient mix shifts more towards third-line patients with less advanced disease, we expect this will extend the average treatment duration. Second, this is a chronic disease with the potential for patients to stay on therapy for long periods. Of the patients who started Nictinvo at launch in the first quarter of last year, 60 to 70% remained on therapy in the first quarter of this year, highlighting the potential for extended durations of therapy, especially as our patient mix shifts more towards third-line patients. Our clinical trial experience shows the duration of therapy can be measured in years for a meaningful proportion of patients. Third, Nictimbo has a broad and productive prescriber base and strong commercial synergies for both syntax and insight. Virtually every bone marrow transplant center in the US has prescribed Nictimbo and all have become repeat customers. Physician feedback is very positive. They continue to report strong activity in multiple organs with particularly notable results observed in patients with lung and skin fibrosis, some of the most challenging to treat manifestations of the disease. All these drivers put us in a strong position to expand our impact third line plus chronic GVHD, the $2 billion US market opportunity, as we can see on slide 10. In summary, our quarterly results underscore the strong demand for Revuforge and Nictimbo and the substantial commercial opportunities we have with both products. We have the right medicines, the right team, and the right strategies to continue delivering for patients and driving strong and sustainable growth. With that, I'll hand the call to Nick to discuss their development programs.

Thank you, Steve. Starting with Revumenib on slide 11, we've made significant progress advancing our pivotal frontline trials and our integrated evidence generation plan designed to establish Revumenib as the main inhibitor of choice across the acute leukemia treatment continuum. I'd like to highlight a few key points. First, we're focused on advancing enrollment in our pivotal frontline trials, which have the potential to support additional FDA approvals and the registration of revumenib outside the U.S. We are well positioned to be the first to deliver pivotal frontline data for amenin inhibitor. Global site activations and patient enrollment are well underway in these trials, which were informed by a robust body of clinical evidence, allowing optimization of endpoint assumptions and other aspects of the study design. We've also been able to leverage the strong relationships we've built with leading investigators and patient advocacy groups around the world through our work pioneering this new class of therapy. To support these collaborations and rapid enrollment, we have a team of highly qualified and well-connected MSLs located in key geographies, including Asia, fully focused on Revumanet. As a reminder, EVOLVE-2 is the phase 3 trial of revumena plus venetoclaxonazacitidine in newly diagnosed unfit MPM1 or KMT2A AML patients. This trial, conducted in partnership with the highly regarded Hovon-Nekwog, was the first pivotal frontline trial of a MENA inhibitor to begin enrolling patients. evolve as dual primary endpoints of complete remission and overall survival, both in the NPM1 population, to support the potential for accelerated and full approval, respectively. Reveal is the Phase III trial of Revumenoid plus intensive chemotherapy in newly diagnosed fit NPM1 patients, including adults and children 12 years of age and older. Reveal also has dual parameter endpoints of MRD-CR and event-free survival to support the potential for accelerated and full approval, respectively. In the fit KMT2A population, we are pursuing a novel and differentiated approach. In addition to generating further data in combination with intensive chemotherapy in partnership with the National Cancer Institute, we are progressing the RAVEN trial with leading clinical researchers. RAVEN is a phase two trial of ravimenib plus venasa in newly diagnosed KMT2A patients who would be considered fit for intensive chemotherapy. The design of RAVEN is supported by the strong activity observed with Revumena plus Ven-HMA in KMT2A patients and growing physician interest in moving from 7 plus 3 intensive chemotherapy backbones to more tolerable Ven-HMA backbones. The second point I would like to highlight is that we will continue to advance our scientific leadership in men and inhibition with a major presence at key medical meetings, including at least 15 Revimenib abstracts accepted for presentation at ASCO or IHA. The volume and breadth of the data we will present underscore physicians' interest and commitment to Revimenib with its differentiated profile and strong activity across multiple genetic subtypes. I'd like to highlight now some of the key data sets we expect to report in the second quarter of 2026. First, we expect new real-world evidence with Revumenib. This data set will build on the first real-world evidence that another group, Moffitt Cancer Center, presented for Revumenib and the therapeutic class at ASH last year. Moffitt reported a 77% overall response rate and 75% MRD negativity rate among relapsed refractory MPM1, KMT2A, and NUP98 acute leukemia patients, who primarily received Revumenib as part of combination therapy. In addition to showing compelling clinical activity, Revumenib was well-tolerated as a monotherapy and in combination with standard of care therapies. We also expect new post-transplant maintenance data, including a data set accepted for oral presentation at ASCO. These will be important data sets given physicians' growing interest in using Revumenib post-transplant. The upcoming data will build on retrospective data presented by MD Anderson at ASH last year from 10 pediatric KMT2A or NUP98 rearranged patients. They reported that Revumenib was well-tolerated in the post-transplant setting with encouraging early efficacy. Notably, all patients were alive and 90% were relapse-free at a median follow-up of 19 months. Additionally, we expect updated data from our Phase 1 trial of Revumenib plus intensive chemotherapy in newly diagnosed NPM1 KMT3 or NUP98 AML. You will first see an abstract with a data cutoff that is similar to the preliminary 708 data we presented at ASH last year, showing high rates of response and MRD negativity, along with a favorable safety profile. Data with longer follow-up will be presented at the meeting. We also anticipate updated data from the relapsed refractory cohort in the SAVE trial of Revimenib plus Venatoclax and Decitabine as said as Uridine in MPM1, ChemT2A, or Neut98 acute leukemias. This update will build on the compelling data previously reported from SAVE, which shows overall response and MRD negativity rates above 80% in heavily pretreated patients. And finally, we expect additional relapsed refractory NUP98 rearranged data from our Augment 101 trial and expanded access program. NUP98 rearrangements, which are found in up to 5% of AMR cases, are associated with a poor prognosis and high unmet need with no approved targeted therapies. Last year at IHA, we presented the first and only data to our knowledge showing compelling activity with a menin inhibitor in NUP98 patients. This data was met with strong enthusiasm by clinicians, and we are already seeing academic centers treating relapsed refractory NUP98 patients with revimenib, underscoring the benefit of having one menin inhibitor with activity across multiple subtypes. NUP98 is one of several subtypes associated with acute leukemias associated with upregulation of Hox genes that may be sensitive to revimenib. Altogether, more than 50% of AML patients may have a genetic alteration which is susceptible to revimenib. The body of evidence supporting revimenib will continue to grow throughout 2026, with additional data expected in the second half of the year, including an update from the BEAT AML trial of revimenib plus vaneza in newly diagnosed NPM1 or KMT2A AML, We also expect an update from a phase one trial of Revimenib plus Giltiritinib in relapsed refractory patients with a FLT3 mutation and an alteration associated with Hox overexpression. Early data presented at Ashlar Sher showed the combination appeared tolerable with early signs of efficacy supporting continued evaluation. For the subset of relapsed refractory NPM1 patients with FLIP3 commutations, amenin plus FLIP3 inhibitor combo is one of several potential options that physicians may consider depending on patient-specific factors. I'd now like to turn to axotilamab development on slide 12. This will be an important year with two upcoming data readouts. We are now expecting top line data from the phase two trial of axotilamab plus roxalicinib in the fourth quarter, a timeline which pulled in due to faster than anticipated accrual. Data from this trial could inform the potential for axotilamab in earlier lines of chronic GVHD and potentially pave the way to a steroid sparing approach. We also expect top-line data from our Phase 2 MaxPyRE IPF trial in the fourth quarter. Earlier this year, we completed enrollment and actually exceeded our original enrollment target of 135 patients due to the number of patients put into screening as we neared the end of enrollment. This speaks to investigative enthusiasm for axotilumab and the desire for new treatment options in IPF. Given the high interest in this program, I will highlight the evidence supporting the scientific rationale for CSF1R inhibition and outline the trial design. Moving to slide 13. Significant evidence points to CSF1-dependent monocyte-derived alveolar macrophages as a promising new target in IPF. These cells are believed to play a key role in driving lung fibrosis. Multiple studies implicate the CSF1R pathway in IPF and provide strong mechanistic rationale for our program. For instance, high CSF1R levels are observed in IPF patients versus healthy controls, and higher levels of CSF1R and monocytes predict shorter survival among IPF patients. Turning to slide 14, axotilamab is an IgG4 monoclonal antibody, which is optimized for diseases with an inflammatory and fibrotic component. It binds to the CSF1 receptor on the surface of monocytes and macrophages, preventing their activation by CSF1 and IL-34. This reduces the levels of circulating pro-fibrotic and pro-inflammatory monocytes and monocyte-derived macrophages and inhibits the activity of these pathogenic macrophages in tissues. Based on these observations, axosilumab has the potential to make a more pronounced impact on the fibrotic process by targeting pathways that sit upstream of the pathways engaged by currently available IPF therapies. The IPF program is supported by the remarkable activity observed with axotilamab in chronic graft-versus-host disease. 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 MaxPyre, nearly 50% achieved a lung response and over 90% reported improvements in shortness of breath at rest. These data, together with the strong mechanistic rationale, are driving strong physician support for axotilamab's potential in IPF. Slide 15 shows the design of MaxPy, a phase 2 randomized double-blind placebo-controlled trial of axotilamab in approximately 135 IPF patients. This is a well-designed trial that has the potential to provide robust proof-of-concept data for axotilamab in IPF to inform a registrational program. The inclusion criteria is similar to other recent IPF trials. Background antifibrotic therapy is allowed but not required, and the primary endpoint is the annualized rate of decline in forced vital capacity, or FVC, measured at 26 weeks. In summary, we have a data-rich period ahead and are laser-focused on executing our pivotal programs. We are just starting to demonstrate our ability to translate promising science into novel medicines for patients with hard-to-treat diseases. With that, I will hand the call to Keith to discuss our financial.

Thank you, Nick. Earlier this afternoon, we reported detailed first quarter 2026 financial results on our Form 10Q, and I'll now highlight a few key points on slide 16. Total revenue for the first quarter was $64.9 million, up 224% over the same period last year. Demand for revenue forge remained strong, with $48.9 million in net revenue, up 144% from the same period last year. We achieved these results even with typical first quarter dynamics, including severe winter storms, which had a transient impact on both products in February, and a growing number of KMT2A patients temporarily pausing Reviforge to proceed to transplant. Inventory levels remain within the two to three week range we have previously guided. We expect continued growth over the coming quarters as adoption in NPM1 increases and the average duration of therapy extends as Reviforge is used earlier in the treatment journey and the number of patients on therapy post-transplant continues to build. Now I want to turn to Nictinvo, which continues to be an important cash flow contributor to Syndax, with our 50% share of the net commercial profit totaling $15.9 million in collaboration revenue in the first quarter. The collaboration revenue that we reported was 29% of the Nictinvo product revenue reported by Insight within the range of 25 to 30% that we've been guiding to. Our collaboration revenue for the first quarter is a significant step up from the 0.2 million in collaboration loss we reported from the first two months of sales of Nictinvo in the first quarter of 2025. We continue to expect our Nictinvo margin contribution defined as the collaboration revenue recorded by the company as a percentage of Nictinvo net sales to be in the 25 to 30% range in the near term and increase longer term as sales grow while much of the expense base stays largely fixed. We anticipate continued growth throughout the year as Nictinvo is increasingly used in the third line and duration of therapy extends. With regard to expenses, guidance remains at 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. We are well-funded to continue investing in our commercial and development priorities with $352.1 million in cash, cash equivalents, and marketable securities as of March 31st, 2026. With this robust balance sheet, growing revenue from two medicines, and stable expenses, we are on our way to reaching profitability. With that, I will hand the call to Michael for closing remarks.

Thank you, Keith. Looking ahead, we are focused on driving revenue growth and delivering on the milestones shown on slide 17, which will fuel further innovation and support value creation. We are in a strong position with multiple near and long-term growth drivers supporting both of our medicines. Revuforge is poised for further growth as we expand into NPM1 and continue to penetrate the KMT2A market, a segment where Revuforge is the only approved therapy. A growing number of KMT2A patients are proceeding to transplant, outpacing our near-term expectations, and returning to therapy post-transplant, which will extend the average treatment duration and drive durable and sustainable growth. With the broadest label and best efficacy profile of the men in class, we have the unique opportunity to cement Revuforge as the menin inhibitor of choice in relapsed refractory disease and ultimately be the first to frontline, unlocking a $5 billion plus market opportunity. Nictimbo continues to be a meaningful contributor to our bottom line. We have ample opportunity for further growth in our first indication as our patient mix evolves and important readouts later this year in frontline chronic GVHD and IPF that could open transformational multi-billion dollar markets in the near term. I will close by thanking everyone who has made it possible for us to deliver breakthroughs for patients, especially the individuals and clinicians who have chosen to participate in our clinical trials, as well as our dedicated syntax team and the long-term investors. With that, I would like to open the call for questions. Operator?

At this time, I would like to remind everyone that in order to ask a question, press star and 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 for just a moment to compile the Q&A roster. Okay, the first question is from Anupam Rama from JP Morgan. The line is open.

Hey, guys. Thanks so much for taking the question. Just a quick one on RevuForge. I know that later this quarter you're going to have data from that multicenter real-world study that you highlighted in your opening comments. What should we be looking for in that presentation beyond what we learned in that Moffitt study that you highlighted? Looking for data points that might help us understand how physicians are using the product and how we should think about extrapolating to the revenue trajectory of the product moving forward. And will this real-world study include both the KMT2A and MPM1 experience?

Anupam, thanks for the question. Very important new data coming, so we're excited about that, and I'll pass it to Nick to give you a little bit more detail.

Yeah, thank you. I'm not going to talk about the data specifically, but I'll give you a flavor of the things to look for as you would anticipate in these types of data set. I mean, one is we're expecting, you know, broad coverage across the genetic subtypes. including NUP98. As previously seen, what we're seeing in the real world is extensive use in combinations of therapy. That's clearly not part of our current indication, but given the data we've generated, we know that physicians like to use it in combination in early lines of therapy. I think the other things I would say to look out for is, you know, the number of patients that are progressing to transplant. because of those catalysts and factors for that, the number of patients that are able to get to transplant, I think that'll be an important data point to look for. And then, of course, the ability to get patients onto maintenance. Now, that's not, again, something we're promoting on, but it's an important part of patient care. Physicians are wanting to do it. We want to provide data, and we are observing it in the real world. So those are the things I'd be looking out for as we generate more real-world evidence.

Thanks so much for taking our question. Thanks, Anupam.

The next question is from Corrine Jenkins from Goldman Sachs. The line is open.

All right, I was muted. Good afternoon, guys. Maybe quickly from us, is there a way that you can kind of help us quantify the headwinds to revenue or patients you're facing? in a given quarter, 50% of the KMT2A population is going to transplant, recognizing that that normalizes once you reach a steady state of KMT2A penetration. And maybe on that note as well, I think you've commented at the end of 4Q, you were at about 50% penetration in the KMT2A market. Is there an update on that plan as well? Thanks.

Yeah, thanks, Corinne, for the question. So I'm going to hand it over to Steve. Maybe I'll handle the second part of the question first, which is sort of the state of the KMT2A market, which is certainly growing. We had gotten to roughly approaching 50% penetrated on an incidence population of about 2,000 patients last year, and we continue to see that progressing. Certainly, the impact on maintenance is a big growth driver for that business. We do think we'll get nicely north at 50% this year, but I do believe that the maintenance piece is such a considerable part of what grows in the future as more patients are now going to transplant. We have about 50% of patients going to transplant and right around that number coming back. But I think that's likely to grow considerably in the coming year or so. And that's driven by what we hear from physicians and all the data that will be coming out. Nick mentioned some should help with that growth rate. But that's KMT2A, very healthy piece of our business. But maybe I'll turn it over to Steve for the other.

Yeah, I think it was the same question around came to today. I think the first part of the question was just headwinds, and maybe that's around bringing patients back in that in that post transplant setting. I think what we've looked and some of the numbers we've updated this quarter using claims data, and we look back and we realize there's a greater percentage going to transplant in this increasing number coming back post transplant. The way I think about it is average is probably three to four months to get patients back. But the longer we're on market, we realize there's patients that may be six months or more off treatment from that transplant to when they get back on. So the timing is going to be important. We've seen that grow as an important piece of our business. It's a little slower to build than it would be just bringing new patients in, which is you know, driving the business right now on the MPM1 side. So, you know, in terms of that, because it all lands on duration of treatment, which is something we've seen extend, and particularly I think we have this in our notes, the patients that do come back, particularly those that start in the first seven months of launch, they're already at nine months and longer in terms of duration of treatment. And that will extend, and there will be more folks in that group over time, which is why we expect the duration of treatment to grow considerably over 2026. Thanks.

Thanks, Greg.

The next question is from Phil Nadeau from T-Day Cowen. Phil, your line is open.

Thanks for taking our questions. Two from us, one commercial and one on the pipeline. In terms of the NPM1 penetration, what do you think is gating for increasing that penetration? Is it simply time on market or are there data sets that could be important, such as the FLT3 combo data that's expected later this year? That's first. And then second, on the pipeline, the data you present from lung involvement in CGVHD is very impressive. What is the time course of the responses in GVHD? Is 26-week duration likely to be sufficient in IPF? Thanks.

Great. Thanks, Phil, for the question. So the first question related to sort of what's gating relative to the growth of NPM1. Maybe I'll turn it over to Steve to make a comment there and maybe to Nick for the pipeline question.

Yeah, MPM1, it's, you know, clearly we're at the front end of that population, Phil, so there's a lot more patients to grab. I think when you think about our own business, there's been step-ups in the business, and it really began for us in that Q3 timeframe, right? At the end of September, we got NCCN guidelines, and then obviously the full indication for the fourth quarter. So we've seen big step-ups in our own business, roughly in the 250 range in Q3, new patients, a big step-up in Q4, another step-up in Q1. Our average is, you know, we're looking at 330 patients new patients in the quarter. So that'll build. It's a different market. You know, KMT2A was obviously our launch. Lots of patients came in. There's REV is already the standard of care. Patients had no other options. We know for MPM1, they do. There's FLT3 commutation, so it's a little bit more complex. The patient tends to be older. We're not going to see as much likely transplant and then restarts in that population. So we're going to give it time, and the time to peak will just be a little bit longer in the MPM1 population relative to KMT2A.

And I'll just add that the profile that we're showing for NPM1 is best in class. I think we feel very confident. Physicians tell us that time and again that we have, as Steve said in his remarks, broad advantages across the profile. So we feel very confident that we'll continue to build that market, build that business and have dominant share over time. Now, the next question was related to IPF, and I'll turn it over to Nick to answer that.

Yeah, thank you, Phil. Happy to take that question. So first thing I say, this is a very robust and statistically rigorous proof of concept study in IPF. And we're very confident in the 26-week endpoint. There have actually been some other previous POCs that have even looked at 12 weeks. We think 26 weeks is a very good compromise in terms of it being too short, but enough time to be able to detect a difference. We actually annualize that. We'll report annualized rates of FVC decline. using standard FDA-approved models for modeling that out to 52 weeks. So this will be a very rigorous proof of concept to inform a Phase III program. And if you look at previous Phase III studies, if you actually look at the graphs for separation, you see very clear separation by week 26. So we're confident that 26 weeks will be sufficient to detect a difference and inform a Phase III.

Perfect. Thank you. Thanks, Phil.

The next question is for Brad Canino from Guggenheim. Brad, your line is open.

Hey, just following on the previous question of the transplant maintenance dynamic continuing to be more of a temporary headwind for now, my question is really simply, when will this start to flip to a tailwind? It sounds like there's two levers now. You're pointing to flat quarterly patient starts, so you're refilling the population, but how much higher than a 50% transplant rate can even be possible in this population. Are you topped out there and now you can grow that maintenance restart? And then are you confident in that six-ish months now wait to the restart for maintenance? Or could that even extend too to be, you know, patients starting seven, eight, nine months later and push out the time to that start of the tailwind as well? Separately, it looks like you lost about 14 points of year-over-year growth due to gross to net, is there a chance that reverses back later this year? Can it get worse? Or should we think about that being a neutral effect for the rest of the year? Thank you.

Great, Brad. Thanks for the questions. So I think you're right about the maintenance dynamic is today is a bit of a headwind. I mean, obviously a great opportunity for patients, many more going to transplant. It's far exceeded our expectations. You've probably heard us talk about the fact that maintenance could, or rather transplant could get as high as 50%. And that's essentially where we're at. So I think that happened a little bit faster than we expected, but that's probably where it'll be. I don't expect it to be much higher than 50%. So I do think that has sort of topped out. We will ultimately see, but that's point number one. Point number two is the effect on restarting and how long we're going to need to wait until that really becomes a big factor. We have talked to many physicians. Obviously, the work that we've done seems to indicate that we'll get to 70% to 80% of patients restarting maintenance. And we've seen that accelerate as every quarter has gone by. So I think that's an important milestone or important bogey for us. Whether that takes another quarter, two quarters, a year, we'll see. We ultimately think that's where we'll be at steady state. So that'll be an important driver of growth as we go forward here. And that's the dynamic we see playing out. We do see patients, as Steve mentioned, that over a six-month period of time, as you wait to come back and engraftment for maintenance, it's a little bit longer than we expected. We are picking up patients now in the claims that it's not three, four months of engraftment and restart. It's more like five, six months, maybe even longer. So that, again, that is a piece of this. I don't think that's the vast majority of patients. I think that's some of the patients. So again, we do expect in future quarters to start to see some of the compounding effect as we sort of peaked at our 50% transplant rate, and then we'll have more patients coming back. So that's the dynamic to look forward to. Maybe, Keith, do you want to talk about growth to net?

Yeah, Brad, with respect to gross to net, I would just say, not sure exactly of your math, but I would say that we've consistently guided since we launched that we expect gross to nets to settle in the 20% to 25% range. We're still squarely within that range, and I'm not changing our guidance at this time. We did see what I would call typical 1Q seasonality impacts on the gross to net just due to the high deductible, mostly due to the high deductible commercial resets and the Part D donor hole, but the impact still landed us within the guided range.

Thank you. The next question is from Stephen Wiley from Stifel. Stephen, your line is open.

Hey, good afternoon. This is Josh on for Steve. Thanks for taking our questions. Do you think that the data from the phase two AXA-RUX combo trial would be sufficient to potentially support a compendia listing for frontline GVHD? And then how do you think data from this trial will serve to inform or de-risk, if at all, the phase three trial looking at AXA in combo with steroids in the frontline setting?

Thanks, Josh. Good question. So let me turn it over to Nick to handle both of those, I think.

Yeah, I think it's a very, it's a well-designed study and a very interesting hypothesis that you might be able to avoid steroids in the frontline setting. So this is a potential steroid setting approach. It's 120 patients, about 40 patients per arm, and is basically, I mean, it's a non-comparative randomized study, but really the benchmark for this is about a 40% response rate using standard NIH criteria at around six months. So if you see a meaningful improvement on that, let's say 60%, which is kind of aligned to where the study would be, I think that could not only inform clinical practice, but potentially also compendial listing just because of the morbidity associated with long-term dexamethasone. We will also look at a number of other clinically meaningful endpoints in that study, like the time to actually have to reintroduce steroids. And if you can really delay that again, I think clinically that's significant. Duration of response and time to events or other endpoints. And I think when we look at the totality of those, it'll be very informative, both the practice and compendia. and could inform future registration studies. The dexamethasone combination phase three study that you mentioned is a different hypothesis. This is where the axotilamab can actually add to dexamethasone. So it's a slightly different hypothesis, and that could offer an alternative standard of care. They have quite complementary mechanisms of actions, and that is a pivotal phase three study.

Thank you. The next question is from Faisal Khurshid from Jefferies. Faisal, your line is open.

Hello, this is Inanchan for Faisal. I wanted to follow up on the progress in the first line AML phase three trials. Where do you see yourself relative to the competition there and maybe a little bit more on Evolve 2 and how you see that stacking up in the end? Thank you.

Thanks, Anand. So let me first comment, and then I'll let Nick make other comments. The progress on the trials, we're doing quite well. I think as Nick remarked, or in his written remarks, you know, we have, this is a period of standing up our trial, standing up sites, enrolling patients, everything is on track and going quite well. So we feel we are, you know, going to be first to frontline. We feel confident in everything that we're doing to execute against our timelines. And so everything's on track. And I'll turn to Nick, maybe more about Evolve.

Yeah, no, thanks. And this is, I mean, simply, this is one of the highest focuses for my teams. It's a very high priority and we're spending a lot of time on this and we have two different approaches evolved to, again, this was the first study started enrolling. So it's been enrolling now for nearly a year. We're working with Hovon, which is giving us a fantastic network of sites across US. And we are also now entering sites in the US, making a lot of progress with site activations and in deep patient enrollment. In fact, Some of the metrics around patients per site per month are actually somewhat in excess of what we modeled. And that's quite exciting because I think it speaks to the physician's enthusiasm and the support of the Hovon group to enroll this study. So because we've generated such a body of evidence with Veneza, we actually feel very confident in the design and some of the statistical assumptions of that study. And it's moving along very nicely. And our expectation is to be first with the readout for that trial. Likewise, Reveal, we've made a lot of progress. As you know, we recently confirmed the dose at 162.70 in combination with intensive chemotherapy, which is great. We're working with a leading CRO internationally. We're busy setting up sites in Asia and activating sites. And again, we're running very much to track. So we're feeling very confident about that study as well and more on that to come. But no, the teams are feeling confident and we're in a good place.

Thank you so much, guys. Appreciate the call.

Thank you.

The next question is for Mayank Mantami from B Reilly. Mayank, your line is open.

Yes, good afternoon. Thanks for taking our questions and congrats on the progress. Lots going on for you guys. Just any chance you are able to share, you know, the absolute number of patients launched today that have returned post-transplant? And on the 300 new patients added intra quarter, you know, if you can give any color on the mix NPM1 and NKMT2A, which is what we saw in the prior quarter. And if anything on the NPM1, you can share on duration and co-mutation use, you know, relative to what you had maybe initially expected last quarter, that would be great to hear. And then I will follow up.

Yeah, Mian, thank you for the question. So on the absolute number of patients, I think maybe I'll ask Steve to make a comment if we have that data.

We can estimate it. We don't have exact numbers that I would share right now. We know we've treated 1,400 patients roughly from launch date through now. Break it down by KMT2 and NPM1 patients. So it's probably... at least a few hundred at this point, more. So we can come back with that.

Yeah. I mean, look, I think that part of what the challenge of breaking down KMT2A versus NPM1 is it doesn't work like that in claims. So you have to make some certain estimates. So that's a little bit trickier. Your question about commutations was what percent of patients have commutations. I think that was my interpretation of your question. I think broadly speaking, NPM1, a high degree, 85% of patients have commutations. About half of those have FLT3 mutations. So we're running trials to look at combinations and things like that in terms of the FLT3 population. Other patients have IDH mutations as well. So it breaks down as a multifaceted population of patients that you have to deal with with combinations or with, in some cases, we use venetoclax and azacitidine to combine our drug with in order to handle all of that. So I think that's the extent of the commutation question. So we'll leave it there for now.

Duration? Thank you, Michael. Duration of NPM1?

Yeah, thanks. So duration, I mean, we had talked about duration of NPM1 over time being in the roughly seven to nine month range. I think it's early days to look at and have a duration calculation specifically for NPM1. We had talked a little bit more about duration. the KMT2A population and how that's kind of coming together with the impact of more patients going to transplant and returning for maintenance. And as Steve mentioned in his remarks, patients who have actually received a transplant and have gone on to maintenance are on average out to nine months and counting. So that's a very positive forward indicator of where that business is going. And I can think that, you know, NPM1 is certainly tracking with patients staying on drug for multiple months. Some will get transplant, most will not. And so that'll be an impact, you know, a factor in how duration ultimately plays up. But we expect patients to do quite well and, you know, be on drug for months.

Got it. And on the AXA plus RUC study, the phase two, you know, timeline got pushed up. Is the phase three steroid study that, you know, Nick, you just mentioned, is that also tracking ahead of plan? I believe you said early 2028 readout, if you can clarify that. Thanks for taking our questions.

Yeah, I know. That timeline's the same. Nothing's moved out. They're independent of one another, as you said. you know, Nick mentioned in the trials are different trials and they have different, everything's different about them. So no, I wouldn't, I wouldn't assume that timeline has changed.

Gotcha. Thank you.

Thank you.

The next question is from Etzer Darut from Barclays. Etzer, your line is open.

Great. Thanks for taking a question. Maybe you could just provide any color commentary or even guide posts on 2026 revenue guidance. And then any color as well or commentary on commercial dynamics with just different NMP1 call points with ZYFTA meta on the market. Anything you can provide there would be great as well.

Thank you. Sure. Thanks for the question. So first, maybe I'll turn to Keith on how we're approaching revenue guidance, which is going to be easy to answer.

Sorry, we don't provide revenue guidance. We're early in the launch of NPM1. There's competition out there, so probably wouldn't be responsible for us to go out and give guidance at this point. Right.

And then anything on the commercial dynamics between us and our competitor? I think that was the genesis of the question there.

Steve? Yeah, I mean, dynamics we can share. Competition is always good for us to be at our best. But I think importantly, menins are exciting. You know, lots of physicians are interested. Awareness is there. It's an obvious path in KT2A. We've done very well and met and probably exceeded physician and patient expectations there. The NPM1 patient's different. I think you can see by the nature of these calls, there's co-mutations. It'll build differently over time. So we think it's a good thing that there's another Menin player in the market, raising awareness, finding a place for Menins. We've shared, Michael shared thoughts on just our profile, how physicians think about it. We've got a better profile in NPM1. So anything that's done on behalf of the class will have benefit to us as the market leader in NPM1 and in KMT2A. So- We'll see how it rolls over the coming months, but we think it's a good thing, and we think ultimately we'll benefit from it.

And I would just say that NPM1 is a very considerable piece of our business. It's growing. We feel very good about our competitive position. Steve's organization is essentially built us into the market leader, and we expect to continue to build that piece of the business, competition or no competition. Thank you. Thank you.

The next question is from David Dye from UBS. David, your line is open.

Thanks for taking my questions. Just on the Nick Timbal in IPF, what levels of investigator or payer interest are you seeing today in Nick Timbal's anti-fibrotic potential? And how might positive IPF change, how might positive IPF data change the commercial opportunity long-term?

Thanks for your questions, David. So two questions related to Nick Timbo. One, excuse me, payer interest around IPF. I think that was the first question. Steve, do you have a comment on that?

I really don't. I mean, this is handled. You know, there's interest. There's clearly unmet need, the drugs that are there. don't work incredibly well. So you're going to see payer interest serving that population. Work is generally done by insight.

I mean, what I would just add is that, I mean, this remains an area of high need. It's poorly served by currently approved therapies. I mean, there are three, maybe four therapies approved. None of them are very satisfactory. The survival and prognosis of these patients is very poor. And no drug to date has really impacted the natural history of the disease. So there really is a great need for a drug that could potentially impact the natural history of the disease. And, you know, that's the hope with axotilamab that it might be able to do that. You know, from an investigator and physician perspective, the support we've had from investigators and their desire to contribute in a potential phase three is very high, which I think speaks to their interest in a novel and differentiated approach to the treatment of IPF. So we're feeling very good about that.

And as you know, the market opportunity here is quite large. We're talking about 150,000 patients or thereabouts in the U.S. And this would be a new mechanism for this disease if we're able to show in this trial meaningful impact on the efficacy endpoints and safety outcomes. as well, will, I think, have a very interesting and compelling proposition in IPF to serve patients. So it could be, you know, sort of a, I'd call it a game changer relative to market size. I mean, GVHD is considerable as we've laid out. We think we have a very compelling proposition in GVHD alone. Once you add in IPF, it's a, you know, obviously a completely different size of opportunity in the U.S. for us to get involved. So excited about that. Thank you so much. Thank you, David.

The next question is from . Your line is open.

Hi. Great. Thank you for taking the question. On RAVEN, I had a question. If that study, that phase two looks good, would you then consider a phase three given the regulatory pathway is a little less well worked out relative to what you're doing with REVEAL-ND? That's my first question. And then I was also interested, you know, you mentioned that you're guiding to 50% to transplant up from the 33%, but then you're still restarting about 70 to 80%. I'm just wondering if, you know, why that number was staying the same. If you're increasing the number of going to transplant, I thought perhaps maybe you'd get even more restarting, but maybe that's not the right logic. So just curious to how you think about that part too. Thank you.

Yeah, thanks, Igor. Let me just clarify on the second question. So we had said that we're getting to about 50% patients transplanted. That was correct. What we expect as the target is 78% of patients to come back. Not everybody will come back for maintenance, but the vast majority we expect to get to that point. Right now, we're not there yet, right? So we're at approaching half of the patients coming back for maintenance, that number will grow. It'll grow based on our confidence from the data that we've put together, some of which will be presented in the coming weeks at some of the medical conferences. We've heard from physicians, this is what they expect, expect to put patients back on maintenance. They feel very strongly about that. So this is What we expect will happen, and we feel very confident in that over time, but we're not quite there yet. So that's the dynamic we're experiencing. It's great for patients, many more going to transplant. The actual funnel of patients who are available for maintenance is expanding, and so that's all very positive driver of business going forward. So the second question related to Raven, and I'll turn it to Nick.

Yeah, I'm happy to take that question. And we're excited about this hypothesis because this is a bit of innovation in an area where, you know, patients could potentially get an alternative and better tolerated approach. You know, and these patients would normally get intensive chemotherapy in order to try to get them to transplant. And the hypothesis here is by giving them venet and revumenib. You can get these, you know, fit KMT2A patients, many of them quite young, to transplant without all of the morbidities. Now, in terms of its intent, clearly that's a high, you know, an area of high unmet need. We haven't talked about the specifics of the study design yet, but clearly a compelling result that you get high rates of transplant and good outcomes with a much better tolerated regimen would certainly be you know, informing a clinical practice, potentially guidelines, and we would even be thinking about, you know, how would that support a registrational approach, given the totality of the data we're going to be generating in the frontline setting. So more on that to come, but we think it's a very differentiated and innovative approach to this patient population.

Thanks. Thanks, Raghav. The next question is from Jason Zemanski of Bank of America. Jason, your line is open.

Good afternoon. Congrats on the progress, and thanks for taking our questions. Two, if we may, wanted to return to the subject of Revenue Forge access. There was some discussion last year in the community that some plans were requiring step edits through one-minute inhibitor. You mentioned there was some confusion over the relative cost of Revenue Forge. Was curious as to whether or not this was related, and can you speak to whether or not you're seeing any step edits throughout the universe? And I guess secondarily, you mentioned that about 45% of KMT2A patients were resuming therapy post-transplant. I think last quarter, you cited a range of 40 to 45% of patients. Just curious, what kind of gets you through that barrier of, I guess, 45%? Is this a case of sort of fast adopters and very cautious adopters? And really, what's it take to get more of those docs on board. Thanks.

Thanks, Jason. Good question. So let me start with your question about access, which I'll turn to Steve and he can address.

Yeah. So as you know, the access is great. 97% across both indications, not only a high number, but it did it very quickly. So plans have been reimbursing Revuforge since the launch. So your point about step edits, and I did mention this in my comments, there's literally three plans that have step edits in place, and it's really restricted just to the 270 milligram dose. To not a lot of patients, it's less than 1% of the overall. And some of that came about on a On a monograph, which I also referenced in my prepared comments, a monograph that came out later part of 2025 and just had some incorrect information and made some assumptions just based on dosing, that if you were to exclusively prescribe the 270 dose, you would have a higher WAC than the other men and competitor. We know that that is not the case. In fact, most patients, 75% to 80% of them are not on that dose. So the WAC ends up being lower, about 15% to 20% lower than our competitor. at the one dose that they have. So since the monograph has been adjusted, they've corrected the fact base, they've removed the guidance on a step through our competitor at that dose, and the recommendation is no longer there. Plus, they updated it for other reasons, clinical, non-clinical, so the information is there. So the step... That is in place, is practically ineffective, and physicians get to choose what they want to. So there's, according to our information, there's not one patient that has had to walk through a step for Reviforge to date, and we don't expect that to continue moving forward.

Great. Thanks, Stephen. And I guess the second question relates to maintenance and how do you increase maintenance beyond the 45%. I'll just remind you that we've actually increased the use of maintenance throughout last year. So you saw it kind of go from about a third of patients all the way up to 45%. It is steadily increasing. But we do, as I said earlier, that... Data and real-world evidence will ultimately drive it, and we have a robust strategy in place to deliver to get to this steady state, 70% to 80% point, which will happen at some point in the future. We can't predict exactly when. I was a little off on my 50% prediction. I thought that would happen later and it happened more quickly. So we are very – very bullish on the fact that we will get there. And all the data that we have coming out, and we're very focused on this, should help physicians think through how best to dose patients and at what interval. And some are very cautious about patients coming back from transplant, as you can expect. Their engraftment period varies by patient. And physicians want to make sure that count recovery is well underway and that they're managing patients really effectively. So we help them with that. where there's lots of data that's coming out and ultimately getting to that 78% should be quite achievable. So thank you.

Great. Thanks for the call. Thank you.

Once again, if you have a question, you may press star five on your telephone keypad. The next question is from Salim Saeed from Mizuho. Salim, your line is open.

Hey, great. Congrats on the quarter, guys. In progress. I guess two from us. One on just MaxPyre and then just the other one on the RefuForge chart you provided on slide four. On MaxPyre, Nick, could you maybe remind us, and since it's a robust study, but could you remind us what your power to show the 26-week time plan? I presume the powering was done on the 26th week and not the 52 weeks that you plan to model to. and then what the variability or standard deviation you're assuming on the primary endpoint. That's question one. And then question two, just on RevuForge, I guess like one of the dynamics here, it looks like from this chart, which I thought was super helpful here, it looks like on KMT2A, you guys actually like maxed out sort of at this 200 new patients per quarter pretty quick. Are you anticipating the same sort of dynamic on NPM1 too? to max out with, you know, new patients per quarter within, I guess, like maybe it's three quarters here, so four quarters. And what would be the underlying dynamic why you would max out so quickly? Thank you.

You want to answer the, Nick? Yes, thank you for the question. It's a good question. And what I would say is, I don't want to go into specifics of the statistical assumptions, but I would say it's a very well-powered study. So we plan to recruit 135 patients. We're actually slightly over-enrolled because of the physician support. So we're over-enrolled by about 10 patients. It's a two-to-one randomized study with an FVC primary endpoint. And it is well powered. And we'll look at an annualized rate and we'll use standard statistical modeling to report out the annualized rate. You know, rather than what is powerful, what I would suggest to you is, you know, what we would want to see, because we're actually looking for a fairly significant difference, you know, in order to inform a phase three design. We're not looking for small incremental differences. So, you know, in terms of the rate of decline somewhere in the region of a 40 percent improvement in terms of the decline, The reduction in the rate of decline would be really meaningful. And that's the kind of, you know, based on historical controls, the sort of figures looking at the totality of the data we'd want to be looking at to inform a phase three. And the study is well powered to be able to show that type of difference. So we'll let it read out and look forward to reporting those data in the fourth quarter.

And Salim, I think your second question about dynamics on reverie forage, you know, I'll just simply say that when you think about KMT2A and NPM1, we have not maxed out. I think KMT2A is continuing to grow. As I mentioned earlier, incidence population of about 2,000 patients. These are, so it's a rare disease. You need to find the patients. And I think we are getting as many as are available. We're the only men in that space. We have the best profile and physicians are recognizing that the drug works very well for these patients. So we expect to continue to build that market share well beyond what we're at. And, you know, every quarter is going to be a little bit different. But I feel very confident about that. And then NPM1, same thing. You know, there's no – it's a much bigger market. As you know, it's about two to two and a half times the size of KMT2A. And the opportunity there is large. So we expect to, you know, cover the whole universe and get as many patients as possible. This should continue to grow. In NPM1, it's all about new patients. And then in KMT2A, it's about adding incremental patients quarter over quarter, new patient starts. But I would say the increase in maintenance is a transplant, as we talked about, and maintenance is going to be a big driver of growth for that segment as well.

I guess my question is more at the rate that they're coming in. It looks like that's what's next, not the number of total patients, but the rate that they're coming in. It seems pretty consistent here.

Yeah, we've talked about a consistent rate of new ads, right? So I wouldn't say we haven't penetrated. We'll continue to penetrate and build. It will be a steady new rate of patients coming for KMT2A. MPM1 should be slightly different, larger market, and new patient starts will be more, certainly in the early stages of launch, be significant. you know, more dramatic. But I think the, you know, the businesses and the way the business actually accrue revenue are slightly different as we talked about.

Sure. Okay. Got it. Super helpful. Thanks so much, guys.

Thank you.

Our final question today is from the line of Andre Maldonado from HC Wainwright. Andre, the line is yours.

Hi, guys. Thanks for taking my questions, and congrats on the progress. Just two quick ones for me. First, quick follow-up on axotelimab and IPS. I guess, you know, can you provide a little bit more color on how we should be thinking about the Phase II readout as primarily an all-comer VFC study, or is there a biological subgroup, you know, such that, you know, patients with maybe more monocyte-slash-maybe macrophage-driven inflammation where you expect to break out just based upon the fact that, you know, the CSFR1 mechanism, you know, is stronger there. And then maybe an underlying question for, you know, RevuForge. I guess, you know, as we look at, you know, the NUP98 kind of opportunity, I guess, what would you need to see clinically to treat this as a distinct, you know, expansion opportunity rather than just a scientifically interesting but commercially smaller subset? Thank you very much.

Andrea, thank you very much for the questions.

I'm going to let Nick get into the IPF questions. Yeah, it's a very interesting and, you know, relevant question. Of course, we'll analyze the intensive treat population. Our expectation is that we'll see a benefit, you know, across all comers. These patients are treated on a background of antifibrotic. So we have stratified for by the type of antifibrotic they're on, whether it's intendinib, nifedipine or nifedipine. you know, or no antifibrotic. So we will look at that and we'll look at those subgroups. But given that we know that patients that have high levels of monocytes and high levels of CSF1R, we are expecting that this populate and that that is correlated with a poor prognosis in IPF. We are expecting that the benefit would be seen across the intent to treat population. So that would be our expectation and what we'd be planning to do with the phase three. But certainly, we will look at subgroups, except in a smallish phase two, it's difficult to tease out differences in subgroups. And I'm happy to talk a little bit about NUP98 as well, just to start. Just from a clinical perspective, we have, as you already know, presented data on a small subset of NUP98, where we showed that three out of five patients had a form of morphological remission, which was very encouraging. We are planning to present additional data this year. I mean, biologically, it makes complete sense for these patients with NUP98R that they should benefit from Reviforge. You know, we've seen that across the spectrum. And as we, you know, we plan to publish further data this year, certainly considerations for submitting for the consideration of NCCN guidelines would be something we would be thinking about. So, you know, that's the plan based on the data we've seen for this subset. And we probably estimate it to be somewhere around 5% of the baseline of AML. So it's not an insignificant subset and clearly an area of higher med need because these patients tend not to do very well.

Yeah, I think that's, you know, as Nick said, 5%. I think it's an under, it seems to be somewhat an underdiagnosed area. We hear this from physicians regularly now that Revuforge could be a good option for them. We've been following the Hoxme signature, gene signature, which has, you know, kind of yielded NPM1 and now 98, and there may be other subsets. So the ability to expand even beyond, call it 50% of AML is potentially possible. And, you know, we feel like we're, on the cutting edge to make this hopefully part of the portfolio. So we'll follow up on that, but thanks for the question.

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.

Thank you, Operator. Thank you all. We appreciate everyone tuning in today to discuss our recent progress and the exciting milestones ahead. We look forward to seeing many of you at the upcoming ASCO and EHA medical conferences and, of course, several investor conferences in the second quarter as well. With that, have a great evening, everyone.