Good day, everyone, and welcome to the Syndax third quarter 2026 earnings conference call. Today's call is being recorded. If you'd like to ask a question following the company's prepared remarks, please press star five during the call. At this time, I would like to turn the call over to Sharon Klahre, head of investor relations at Syndax Pharmaceuticals.
Thank you, operator. Welcome, and thank you all for joining us today for a review of Syndax's third quarter 2026 financial and operating results. I'm Sharon Klahre, and with me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer, Steve Closter, Chief Commercial Officer, Dr. Nick Botwood, Head of R&D and Chief Medical Officer, and Keith Goldan, Chief Financial Officer. This call is accompanied by a slide deck that has been posted on the investor page of the company's website. You can now turn to our forward-looking statements on slide 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 10-Q, as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, November 2nd, 2026, only. A replay of this call will be available on the company's website, www.syndax.com, following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.
Thank you, Sharon, and good afternoon, everyone. Let's start on slide three. Syndax delivered another strong quarter of commercial growth and pipeline momentum. Total revenue reached $83 million this quarter, up 82% year-over-year. Demand for both medicines is robust, and we are moving decisively towards profitability. Revuforj net revenue grew to $61 million in the third quarter, underscoring our market leadership in both relapse refractory NPM1 and KMT2A acute leukemia. Similar to prior quarters, we expect Revuforj to account for the vast majority, more than 80%, of the revenue for the class this quarter, a leading position we intend to carry forward. We achieved our seventh consecutive quarter of double-digit quarter-over-quarter Revuforj net revenue growth, driven by a 20% increase in new patients and an increasing number of patients resuming Revuforj after stem cell transplant.
Notably, a growing number of both KMT2A and NPM1 patients are proceeding to transplant after receiving Revuforj. As patients pause treatment to receive a transplant, this creates a short-term headwind that will become a long-term tailwind as more patients resume therapy post-transplant, extending the average duration of therapy and driving durable growth for the franchise. Every indicator of Revuforj demand is positive. The latest data are clear. We continue to lead new menin inhibitor starts across every age group, including age groups where NPM1 is predominant. With an unmatched body of clinical trial and real-world evidence and two years of deep clinician experience in the commercial setting, we are confident Revuforj will remain the menin inhibitor of choice for all menin-dependent acute leukemias.
The clinical impact of our medicine was showcased last week when Revuforj received the prestigious Best Product for Rare Orphan Diseases Award from The Galien Foundation, on the heels of being recognized by TIME as one of the best innovations of 2026. These awards are a testament to our leadership in menin inhibition and the profound difference we have made for patients with some of the most aggressive forms of acute leukemia. Looking ahead, multiple value-driving Revuforj milestones are on deck. As in prior years, Revuforj will have a leading presence at the American Society of Hematology, or ASH, annual meeting in December. New data will be presented from multiple clinical trials and real-world studies spanning the entire acute leukemia treatment continuum, including new frontline combination data that highlight the potential for our ongoing pivotal frontline trials to deliver transformative results.
We remain well-positioned to be the first to frontline with a menin inhibitor, an area of high unmet need and substantial commercial opportunity. With anticipated frontline indications, we expect Revuforj could exceed $2 billion in peak annual net revenue in the U.S. alone. Nearer term, we expect to publish Revuforj data in relapse refractory NUP98 rearranged acute leukemia in the fourth quarter. This landmark publication will inform clinical practice and could support guideline inclusion in a patient population with high unmet need. NUP98 rearrangements, estimated to be found in approximately 2% to 5% of AML cases, are associated with a poor prognosis and resistance to conventional therapies. No targeted treatments have been approved for these patients.
As the first and only company to report clinical activity with a menin inhibitor in this subtype, we have a unique opportunity to pursue a guideline listing that could meaningfully expand the patient population treated with Revuforj. Turning to Niktimvo in chronic graft-versus-host disease, or GVHD. Niktimvo net revenue grew to $67 million in the third quarter, up 47% year-over-year and 12% quarter-over-quarter. Our 50% share of Niktimvo net profit delivered $23 million in collaboration revenue, a meaningful contribution to our bottom line. Collaboration revenue to Syndax is now annualizing at over $90 million, and we expect it to keep growing as we further penetrate fourth and third line chronic GVHD. Positive results from the ongoing combination trials of Niktimvo and frontline chronic GVHD could set a new treatment paradigm and unlock another multi-billion dollar opportunity in the near term.
Beyond moving Revuforj and Niktimvo into earlier lines of treatment, we are advancing our mutant selective allosteric EGFR inhibitor for non-small cell lung cancer and our next generation menin inhibitor for myelofibrosis. Backed by compelling preclinical data and mechanistic insights, both molecules are on track to enter the clinic next year. Each brings a novel mechanism of action to diseases with high unmet need, where we can efficiently generate clinical data that inform and de-risk further development. We took our first two medicines from IND to FDA approval in about five years, and we will leverage that experience to bring innovation to new areas. With a pipeline of promising programs, world-class R&D capabilities, and a solid financial position, Syndax is poised to deliver breakthroughs that improve outcomes for patients and build long-term value.
Before I turn the call over to Steve, I want to sincerely thank Keith Goldan for his many contributions, including leading Syndax's financial and capital strategy during an important time in the company's history and spearheading numerous long-term growth initiatives. After more than four years at the company and over 30 years in the industry, Keith Goldan has decided to retire as Chief Financial Officer. I am pleased to welcome Aaron Ondrey as our new CFO, effective Monday, November 9th. Aaron brings extensive financial and operational leadership experience in biopharmaceutical companies spanning financial management, corporate strategy, and commercialization. I will now turn the call over to Steve to discuss our commercial results in more detail. Steve.
Well, thank you, Michael. Starting with Revuforj on slide four. We delivered strong third quarter Revuforj results with double-digit quarter-over-quarter growth across all key demand metrics and growing commercial momentum. Net revenue totaled $61 million, up 90% year-over-year and 11% quarter-over-quarter. We expect Revuforj to account for the vast majority of all menin inhibitor sales this quarter, highlighting our position as the clear market leader in menin now and well into the future. Total prescriptions were approximately 1,700, up 13% quarter-over-quarter, primarily driven by growth in new patients and an expanding number of patients on therapy in the post-transplant setting. Compared to Q3 of last year, prescription volume has doubled, highlighting the robust business we are building with multiple drivers. As we expected, new starts returned to growth with about 300 new patients this quarter, up approximately 20% quarter-over-quarter.
This increase reflects growth in both new NPM1 and KMT2A patients and creates strong momentum heading into the end of this year. As highlighted on slide five, we estimate that about 50% of new Revuforj patients this quarter were NPM1 patients. Between the new patients and those who started in prior quarters, we estimate our NPM1 business accounted for more than 35% of the $61 million in net revenue this quarter. That is up more than 30% of our net revenue last quarter. Importantly, claims and prescription data indicate we continue to have dominant share of all patients starting a menin inhibitor. Notably, Medicare data show Revuforj accounted for the majority of new patients in the third quarter, as well as all prior quarters. This dataset provides a view of the split of new patients in an age group that is predominantly NPM1.
Claims data also show we continue to have the dominant share of new patients in all age groups, not just the 65 and older group. Turning to the right side of the slide and the latest treatment patterns, as we add more NPM1 patients to our mix, we continue to see Revuforj used early in the relapse refractory treatment paradigm and often in combination with other therapies. Claims data show 75% of use in the second and third line, and approximately 40% of use is in combination. Notably, we are observing robust transplant rates amongst both relapse refractory NPM1 and KMT2A patients treated with Revuforj. While 11% of NPM1 patients in our pivotal trial underwent a transplant following treatment with Revuforj, recent claims data indicate that about 40% of our NPM1 patients are proceeding to transplant, of which about 50% have resumed therapy afterward.
The transplant rate observed with Revuforj is very encouraging and highlights the clinical value of having a medicine with a high overall response rate, or ORR. A high ORR is meaningful because it provides increased chance of being able to proceed to a stem cell transplant, the only potentially curative treatment for relapse refractory NPM1 and KMT2A patients. Notably, approximately one out of two NPM1 patients achieved an overall response in the pivotal trial of Revuforj, a result others have not matched. Importantly, the ORR observed with Revuforj was also clinically meaningful for patients who are not candidates to receive a transplant. Turning to KMT2A. Claims data indicate that approximately 50% of KMT2A patients are proceeding to transplant, of which about 60% have resumed therapy afterward, up from about 50% last quarter.
We expect the percentage resuming therapy will continue to increase as our colleagues in medical report additional evidence from the post-transplant setting in collaboration with leading treatment centers, building on the encouraging data presented at ASCO and EHA earlier this year. Over time, we expect that up to 70%-80% of KMT2A patients will ultimately return to therapy for one to two years based on feedback from thought leaders and our clinical trial and real-world experience. We expect the treatment patterns in relapse refractory NPM1 will be relatively similar to the patterns that we see in KMT2A. As the number of KMT2A and NPM1 patients on Revuforj in the post-transplant setting continues to stack, this will have a meaningful impact on the average duration of therapy and drive durable growth.
The group of patients on Revuforj in the post-transplant setting is already averaging at least nine months of therapy, with this duration expected to increase as we continue to follow patients for time. Importantly, we are also seeing encouraging trends among patients who do not receive a transplant after starting Revuforj. Over half of those patients stay on therapy for a significant period, with an average treatment duration of more than seven months. Moving to slide six. We have an excellent commercial foundation to support continued growth in both our indications. Nearly two years after launch, our broad prescriber base continues to expand, including our activation of tier 1 and tier 2 accounts. More than 90% of these accounts have now ordered, up from 70% prior to the approval of Revuforj in NPM1. Overall, more than 620 accounts have ordered.
That is up about 8% from the prior quarter, reflecting growing adoption in centers of all sizes, including community practices. Notably, claims data indicate Revuforj has a substantially larger prescriber base than the other approved menin inhibitor, and we continue to add more new prescribers and accounts each month than our competition, despite being on the market for twice as long. Patients have reliable access to Revuforj, with formulary coverage in place for nearly 100% of all covered lives for both indications. As we look ahead, we remain confident we will continue to lead this market and deliver for patients.
Our conviction is underpinned by the strength of our product profile, the rapidly growing body of clinical trial and real-world evidence that differentiates Revuforj, and the extensive experience and comfort physicians have built over the past two years, with nearly 2,000 patients treated with commercial drug and hundreds more treated in clinical trials. Switching gears to Niktimvo on slide seven. Niktimvo net revenue totaled $67 million in the third quarter, up 47% year-over-year and 12% quarter-over-quarter. This performance reflects strong and consistent new patient starts and solid persistency. More than 300 new patients were added, and about 6,350 infusions were administered in the third quarter. As experience with Niktimvo grows, physicians continue to report impressive activity in multiple organs, with particularly notable responses in the lung.
We have captured about one-third of the third-line plus chronic GVHD market, with strong adoption in the fourth line and steadily increasing uptake in the third line, driven by a broad and productive prescriber base. Niktimvo is now annualizing at over $260 million and continues to track with the launch of REZUROCK, which reached $500 million in annual U.S. net sales within the first four years of launch in the same indication. Niktimvo is well-positioned for further growth, with steadily increasing uptake in the third line and a profile that allows patients to stay on therapy for extended periods. With that, I will hand the call over to Nick to talk about our development programs.
Thank you, Steve. I would like to start with revumenib, which is on slide eight. We have made excellent progress advancing our lifecycle management program designed to unlock the full potential of revumenib. In partnership with leading researchers around the world, we continue to advance the pivotal frontline trials of revumenib and remain well-positioned to be the first to deliver a menin inhibitor for newly diagnosed AML. Global site activation and patient enrollment is well-established in these pivotal trials, informed by an extensive body of clinical evidence allowing for optimization of our endpoint assumptions and other aspects of the study designs. We are also advancing an industry-leading portfolio of studies in partnership with clinicians at the forefront of menin research. These studies will provide important practice-informing and potentially guideline-enabling evidence across the acute leukemia treatment continuum and multiple patient populations with high unmet need.
We will share the latest results from a number of these studies in the fourth quarter. The upcoming presentations will highlight the unique breadth and depth of clinical evidence supporting revumenib and the vast experience clinicians have established with our medicine. We expect new data in the fourth quarter across three key themes. First is the potential for revumenib to benefit patients earlier in the pretreatment paradigm. Second, the ability of revumenib to bring patients to transplant and its potential in the post-transplant setting. Third, real-world evidence supporting the effectiveness and safety of revumenib, particularly in combination therapy. I'd like to walk through each of these areas separately. Firstly, we expect new frontline combination data that will provide strong support for our ongoing pivotal frontline trials of revumenib.
Updates from the BEAT AML and SAVE trials will provide additional evidence supporting the potential for revumenib in combination with venetoclax and the hypomethylating agent in NPM1 and KMT2A patients who are unfit to receive intensive chemotherapy. Notably, compared to the landmark BEAT AML data published in June, the upcoming analysis will have significantly longer follow-up and report outcomes in a larger cohort of patients. These updated data will build on the previously reported BEAT AML and SAVE data, showing overall response rates approaching 90% and 100% MRD negativity among responders by flow cytometry, along with encouraging early survival data. Additionally, we will provide an update from our phase I frontline trial of revumenib in combination with intensive chemotherapy in NPM1 and KMT2A patients. These data will build on the previously reported results showing high rates of remission and MRD negativity with the triplet, along with encouraging durability and tolerability.
We also look forward to updated results from INTERCEPT. This is the first trial studying the use of a menin inhibitor as a so-called MRD eraser, a research area of high clinical interest. INTERCEPT explores using revumenib to intervene early at MRD or early relapse rather than waiting for morphological relapse, which can trail rising MRD by three to four months in NPM1 patients. Results presented at ASH 2024 from the first 11 NPM1 patients were encouraging. 54% of patients achieved a reduction in MRD, including 36% who actually achieved MRD negativity. We anticipate the presentation of more mature data from a larger cohort in the fourth quarter. Positive results could support the use of revumenib to intervene earlier in the acute leukemia treatment journey.
Now turning to the pre and post-transplant setting, we will present results that highlight the relationship between the robust overall response rate observed with revumenib and its ability to enable a meaningful number of relapsed refractory KMT2A and NPM1 patients to proceed to a stem cell transplant. We also expect the first data from a phase I multicenter trial evaluating revumenib as a post-transplant maintenance. This dataset will build on the encouraging data from MD Anderson presented at ASCO and EHA earlier this year. They reported a two-year overall survival rate of 90% among heavily pre-treated KMT2A, NPM1, and NUP98 patients who resumed revumenib post-transplant, nearly double the historical rate observed prior to the introduction of revumenib. Additionally, we will expand the body of real-world evidence supporting clinical decision-making with new data from multiple centers.
To date, Syndax is the first and only company to report real-world data supporting the effectiveness and safety of our menin inhibitor as a monotherapy or in combination with other therapies in NPM1, KMT2A, and NUP98 patients with relapsed refractory or MRD-positive disease. Previously reported results were encouraging. Those data showed high rates of response, MRD negativity, and transplant, along with evidence of durable ongoing remissions. Our datasets also underscored revumenib's predictable and manageable safety profile, including in combination therapy. Turning to slide nine now and the other programs in our pipeline. In partnership with Incyte, we are advancing a robust lifecycle management program for axatilimab. Two trials of axatilimab in newly diagnosed chronic GVHD are underway. We now expect the top-line results from the phase II trial of axatilimab in combination with ruxolitinib to be reported at a medical meeting in the first quarter of 2027.
The updated timing reflects the goal of presenting a mature and comprehensive dataset that includes not only the primary endpoint of overall response rate, but also key secondary measures such as event-free survival, which will be important for understanding the profile of the regimens. We expect top-line results from the phase III trial of axatilimab in combination with corticosteroids in early 2028. Both of these trials have the potential to impact the treatment paradigm for frontline chronic GVHD. We also recently published data from AGAVE-201 supporting the safety and feasibility of reduced frequency dosing of axatilimab in patients with recurrent or refractory chronic GVHD in Blood Advances. These data show that transition from axatilimab 0.3 mg per kg every two weeks to 0.6 mg per kg every four weeks was feasible and well tolerated.
Patients had a long duration of therapy after the switch, with a median of 21 months, and 84% remained on treatment at data cutoff, suggesting ongoing clinical benefit. This is an important publication that provides physicians with evidence that can inform their treatment decisions. Turning now to our pipeline assets, SNDX-4321 and SNDX-62122. SNDX-4321 is a novel mutant-selective allosteric inhibitor in development for EGFR-mutated non-small cell lung cancer. SNDX-62122 is a next-generation menin inhibitor in development for myelofibrosis, or MF. Like revumenib and axatilimab, these assets have first and best-in-class potential in areas of high unmet need. We expect both molecules to be in the clinic next year and remain on track to submit the IND for SNDX-4321 by the end of 2026 and the IND for SNDX-62122 next year.
Both of these clinical development programs are designed to efficiently generate clinical data that could validate the target and the potential for these two approaches. Our development of SNDX-62122 will be supported by a phase I/II proof-of-principle trial of revumenib in MF that we expect will initiate in the fourth quarter of 2026, with initial data anticipated in the second half of next year. This trial, conducted in partnership with a group of leading MF researchers, will be the first to explore the potential for menin inhibition in MF. With SNDX-4321, we expect to get the first assessment of monotherapy in lung cancer in early 2028. We look forward to sharing more details on both programs as we get closer to advancing into the clinic next year.
In summary, we are executing on a bold R&D vision that aims to deliver novel therapies that transform cancer care with world-class R&D capabilities, strong partnerships with leading scientists and clinicians, and the resources to drive innovation. I have great confidence we will deliver on this vision. With that, I will hand it over to Keith to discuss our financials.
Thanks, Nick. Earlier this afternoon, we reported detailed third quarter 2026 financial results, and I will highlight a few key points on slide 10. Total revenue for the second quarter of 2026 was $83.3 million, up 82% over the same period last year. Revuforj net revenue grew to $60.7 million, and Niktimvo collaboration revenue to $22.6 million. Looking ahead, we expect revenue from both medicines to continue growing and advancing the company towards profitability. The Niktimvo margin contribution, defined as collaboration revenue recorded by Syndax as a percentage of Niktimvo net sales, was approximately 34% this quarter. The margin this quarter was slightly benefited by the impact of a one-time non-recurring adjustment, but going forward, we do expect the margin contribution to be in the low to mid-30% range, an increase from the 25%-30% range we guided to earlier in the launch.
Our guidance for total R&D plus SG&A expenses for 2026 remains approximately $400 million, excluding the impact of $50 million in estimated non-cash stock compensation expense. We ended the third quarter in a strong cash position with $551 million in cash equivalents and investments, and growing revenue from two medicines. We are fully funded to execute our commercial and R&D priorities, including the frontline trials of revumenib and axatilimab, as well as the development of our earlier pipeline assets, just highlighted by Nick. With relatively modest investments in proof of principle trials of SNDX-4321 and SNDX-62122, we believe we can quickly generate meaningful clinical data that creates significant value for the company. And with that, I will hand the call back to Michael for closing remarks.
Thank you, Keith. Moving to slide 11. Syndax is positioned to deliver breakthroughs in cancer care that create long-term value for patients and shareholders. Our first two medicines are improving patient outcomes and generating meaningful revenue to fuel our R&D engine and advance us towards profitability. Revuforj is the market leader in relapsed/refractory NPM1 and KMT2A acute leukemia. A growing number of patients we treat are reaching transplant and resuming therapy afterwards, creating a foundation for durable franchise growth. Our next ambition is clear: be first to frontline AML and establish Revuforj as the menin inhibitor of choice across the acute leukemia treatment continuum. At ASH in December, we will showcase an unmatched and rapidly expanding body of clinical evidence supporting that ambition. Niktimvo is poised to drive continued growth and contribute meaningfully to our bottom line.
Beyond that, two ongoing trials in newly diagnosed chronic GVHD could redefine the treatment paradigm and unlock a new multi-billion dollar opportunity. We are working to realize that potential. We are just getting started. Our proven R&D engine, strong financial position, and two innovative pipeline assets entering the clinic next year position Syndax for long-term value creation as we deliver on the milestones shown on slide 12. Our focus is also clear: deliver first and best-in-class medicines, address major unmet needs, and build shareholder value. To the patients, clinicians, Syndax team members, and everyone who has supported our work, thank you. You have helped bring two much-needed medicines to thousands of patients. That progress is our foundation, not our finish line, and we are ready to build on that momentum. I will now open up for questions.
At this time, I would like to remind everyone, in order to ask a question, 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 will pause for just a moment to compile the Q&A roster. Our first question comes from Anupam Rama with JPMorgan. Your line is now open.
Hi. This is Dilp Dales for Anupam Rama at JPMorgan. Thank you so much for taking our questions. We have two quick questions. Number one, you mentioned the 50%-60% rate of patients with KMT2A and NPM1 AML resuming treatment after transplant. We are curious about what you are seeing in this patient population. Question number two, what are your expectations for the upcoming first-line combo data readout from the BEAT AML and SAVE trials?
Thanks for the question. First question, we are in fact seeing very nice resumption of therapy post-transplant, which is something that we have talked about repeatedly. 50% of the patients who have KMT2A and gone to transplant, 60% of them are now getting maintenance. That is an increase from last quarter. Where we expect it to go, 70%-80% at maturity, that seems to be very much within our reach. That is a very positive driver of growth for us. Actually, in this quarter, we have seen NPM1 grow from transplant rate, which was much lower, we believe, to now 40%, with 50% of patients resuming with maintenance. That of course is a new phenomenon, something that we have seen and are very encouraged by, especially because NPM1 patients are generally older, and this would lead to longer duration of therapy perhaps.
That is a very encouraging second driver of growth for the business long term. Very encouraging overall. Let me turn it over to Nick. Maybe he will talk about the frontline combo and what to necessarily expect.
Yeah. Thank you for the question. We are anticipating presenting a number of frontline data in the fourth quarter. I think you were particularly interested in the BEAT and the SAVE data. So these are combinations with venetoclax and hypomethylating agents. I think we presented these data previously, but I think what is going to be significant from this update is considerably longer follow-up and also an expanded cohort of patients, which is going to give much more meaningful data. When we presented the data previously, we only had seven months of median follow-up, and therefore, the survival data we presented were quite immature. So we are really looking forward to updating the data. What I would advise you to watch out for are probably three things. I mean, one is, again, always we should look towards tolerability and confirm tolerability with an expanded cohort and longer follow-up.
That is always important, that you could combine safely. Number two is the CR rate. This is one of the dual primary endpoints in our EVOLVE-2 pivotal study we are undertaking with HOVON. So look at the CR rate and how it compares with historical controls from, say, VIALE in the mid-low 30s. Then I would really encourage you to look at the survival data with an expanded cohort and longer follow-up. I think this is going to be a much more accurate representation of survival. So those are things we are looking forward to updating. Then I would suggest a similar approach to the SAVE frontline data. In this case, it is with an oral hypomethylating agent, but again, similar, you want to focus on tolerability, the CR rates, MRD eradication, and again, the survival.
Great. Thank you. Thank you so much.
Thank you.
The next question is from Faisal Khurshid with Jefferies. Your line is now open.
Hey, guys. Thank you for taking the question. I want to ask about the competitive landscape. I think we're expecting that it might be possible that we see potential registration-enabling phase II datasets from J&J and Sumitomo, potentially at ASH. Just curious how you think about those programs and how you think Revuforj compares to those. Thank you.
Yeah, Faisal. Thanks for the question, and I'll let my colleagues jump in. Look, I think we haven't seen data, obviously, yet, so we'll reserve judgment until we do. I'll just point out a couple things. Revuforj has been on the market for a few years and will be probably on the market for three years by the time the next competitor beyond the one that's on the market today reaches the market. So that's maybe just one fact. Look, I think whether they have data in KMT2A and NPM1 or just one of the subsets will be interesting to us. But our view on competition is that it's unlikely to be differentiated. We have a very broad profile, believed to be best in class. We have long experience. Physicians are very keen to put their patients on Revuforj with a very strong efficacy profile, which wins in this category.
We are very well positioned to continue our leadership, and we will see data. We will have lots of data ourselves at the upcoming medical meeting, which we are excited to talk about. This will be just one point to discuss when the data does in fact come out. Nick, anything to add?
I would just add, if your question was in relation to frontline, again, we are looking forward to updating the totality of our frontline data, including with intensive chemotherapy. We are feeling extremely confident in the profile that we are seeing across the important parameters that inform our phase III. Those data have really helped us design, I would suggest, a very innovative and efficient approach to our phase III pivotal studies.
We were the first to get a phase III study up and running in the frontline setting back in May 2025. We are feeling very good about the execution of those studies now. We have good momentum. Sites have opened up worldwide and tracking quite nicely. We will be interested to see, of course, what data are presented at ASH. Competition is good for us, but we are feeling extremely confident about where we are and how we are executing on our programs.
Lastly, I would just say that I think that the bar is quite high for competitors to come behind us. We are feeling quite confident about what we have built, and we will be able to leverage that going forward. But thanks for the question.
Got it. On the-
Yeah, go ahead. Sorry.
Yeah, thanks for the answer. Just on that point on frontline, when do you expect to be able to give the street a little more clarity on when to expect frontline data? Because I believe you're not the only company that says that they're first to frontline. Thank you.
Sure. No, look, I think we feel quite confident in our ability to get to frontline first. As Nick mentioned, we have probably the broadest set of data presented to date, quite compelling data, and we're going to update those datasets at the upcoming medical conference. Our execution is on point, opening up hundreds of sites worldwide, enrolling patients, so the momentum is there. We feel really good about how this is going. In terms of updating our guidance or informing the street on exactly when we'll complete enrollment and get to potentially an approval, that will come in time. I think there's, for us, obviously, it's a competitive space and doesn't seem to be the right time to necessarily update on that, but we will, of course, do that at the right time.
Got it. Thank you.
Thank you.
The next question is from Ellen Horste with TD Cowen. Your line is now unmuted.
Hi, guys. Congrats on the quarter. I am just wondering, with a year or so of commercial use now in the NPM1 population, what can you tell us about the duration of Revuforj therapy in this population among the patients that do and do not proceed to transplant and eventual maintenance therapy? How should we think about the incremental benefit from use in the post-transplant setting? Thank you.
Yeah, Ellen, thanks for the question on NPM1 use. Maybe I will take a shot at it, and maybe Steve, if you want to chime in here. Look, duration is very encouraging. Overall, I think we have mentioned and guided to that we would expect to be in the 6-12 month range for patients who receive a response, and I think we are nicely in that range. For NPM1 patients, what was encouraging this quarter is many of the patients are actually going to transplant, 40%, and that half of those patients are resuming maintenance, which, as a headwind in terms of revenue today, will be a tailwind tomorrow, and especially so because they have longer duration when they get maintenance. So, that is very encouraging.
When we look at the patient population of patients who have not gotten a transplant but have gotten to response, we are talking about seven-plus months of duration. That is for patients who, predominantly NPM1 patients. They are doing well, and we expect that to continue and build as we go quarter-to-quarter and more patients come get transplanted and then get maintenance. I do not know, Steve, anything to add to that?
I think the only thing to add is that the drug is outperforming in the real world than it did in the clinical trials. We have been talking for several quarters on the evolution of the KMT2A patient moving to transplant. We have seen that transplant move up to 50%, possibly could go higher over time. As Michael Metzger mentioned, the increase to 60% of patients returning post-transplant is encouraging. It could certainly go higher than that. But the NPM1 patient, if we looked at the clinical trials, about 11% of patients went to transplant. We are seeing earlier stage patients, about 75% are first and second line. Combination treatment is in 40% of patients. I think physicians were unlocking, and this may not be just a menin effect, this could be a Revuforj effect in that NPM1 patient.
40%, first time we revealed that in a quarter, so that is new information, of patients moving to transplant that are NPM1 patients, and 50% returning post. As Michael Metzger mentioned, short headwind now, but the tailwind is going to be significant. You are seeing patients stay on much longer. The longest duration of treatment is going to be that transplant, post-transplant start. That group will grow, and as mentioned, if they are not fit to go to transplant, that duration is also increasing over time. We feel like we are in a very, very good spot heading into the end of the year into next year.
The next question is from Stephen Willey with Stifel. Your line is now open.
Yeah. Congrats on the quarter. I also just want to say, great working with Keith and wish him all the best in his work. Quick question on the NPM1 transplant rate that you are seeing. I know that you kind of alluded to it. This is, the 40% is higher than what was thought for this patient population. I know it is probably more than 2X what most of the KOLs have told us. Do you think that this is a durable trend? Do you think this has something to do with just the onboarding of new patients just having a certain phenotype? I would just be kind of curious how you think about the durability of this 40% getting to transplant. I then just have follow-up.
Yeah, Steve, thanks for the question. No, actually, what I think is happening, what we hear from physicians is that we are treating patients earlier, we are treating them in combination, and they are getting to response. I think that is essentially true for KMT2A, but it is also true for NPM1. We are having great success in getting them to a response. Remember, in our trial, we treated later line patients, and we had a 50% overall response rate. We believe that by treating them earlier and treating them in combination, you can drive a higher percentage of patients into response. I think that is what is getting patients to a transplant, the ability to bridge that and get them there quickly.
Ultimately, the fact that they receive less therapy over time, meaning, if you treat them earlier, they do not get as worn down from subsequent therapy, you can get them onto maintenance. I think that coupled with the fact that physicians have told us that transplant techniques have improved, and that allows for more flexibility in how you treat these patients. The openness to transplant and maintenance seems to be quite real to us and encouraging. I do not know, Nick, if you have anything to add on that front?
Sum it up.
Yeah. Okay. Steve, that's what we got.
Okay. Just a quick follow-up. I know the extension of the frontline Niktimvo, axatilimab steroid data was pushed into the first quarter. I know it sounds like that was a byproduct of wanting to be able to present some durability data. Can you just remind us what the kind of benchmark durability data is in terms of response duration with steroids in the frontline, and I guess just kind of any ballpark estimate of what you think would be clinically meaningful in terms to exceed that? Thank you.
Yes. Thanks for the second question, Steve. I'm going to turn it to Nick.
Yeah. Thank you, Steve. As you heard, we've moved it into Q1 and hope to present it in Q1 in order to present the totality of the data. We talked previously about the primary endpoint, which is the response rate at six months, where we're anticipating a benchmark historical for steroids of around 40%, the alternative hypothesis being around 60%. We'll be able to present that. Then I think it's important to present both the duration of response and the EFS.
Now, it's not built into the statistics, but if you look at roughly what you'd expect for the EFS for steroids alone, it's probably of the order of six to seven months, and I would anticipate that an increment of that of the order of three to four months would be quite clinically meaningful to physicians and patients to avoid them having to have a steroid regimen and all of the morbidity associated with having to take dexamethasone. That's the sort of order of magnitude we'd be hoping to see a difference in. But obviously, we'll look forward to reporting those data in totality in Q1.
Very helpful. Thanks for taking the questions.
Thanks, Steve.
The next question is from Etzer Darout with Barclays. Your line is now open.
Hi, this is Gustav on for Etzer. Thanks for taking our questions. Two quick ones for us. The first one is on the AGAVE-201 data that showed the transition from 0.3 to 0.6, Q2 to Q4 weeks. What is the significance of this data moving forward? Number two is around the combination use, so it is about 40% still. At this point, are you able to tell whether the combination use is associated with higher transplant rate or longer duration of treatment or deeper responses in the commercial setting? Thank you.
Maybe I will turn it over. Thanks for the question, Gustav. Let me turn it over to Nick about the AGAVE-201.
Thank you for the question. I think this is a very patient-centric approach. I mean, I think the simple clinical benefit is that you are able to transition a patient from a two-weekly IV to a monthly IV with comparable tolerability and prolonged duration of therapy. That is what we have shown in the manuscript and in the publication, and I think that is a benefit to patients. That is something that could ultimately inform guidelines and potentially even inform labeling in due course, which is a consideration. Again, I think it is a patient-centric approach, just requiring less healthcare burden and importantly, less burden for the patients to have a four-weekly infusion as opposed to two-weekly.
The second question, I guess, is about combo use and the 40% that we are seeing, and really what is the breakdown of that percentage and what is driving them there? I do not know, Steve, do you want to make any comments?
I'd probably pass to Nick. I think the claims data doesn't really
Yeah.
It's a subset.
Yeah.
We haven't shared data previously, but I think-
We've seen, I mean, I think there's a drive. Because we've presented such compelling data of revumenib in combination, I think particularly with venetoclax combinations, there is a desire for physicians to use revumenib in a combination with a variety of different chemotherapies. We will be updating later this quarter a few real-world series from multiple centers that I think really emphasizes the desire of centers to use revumenib in combination when they can, because you get much higher response rates. And the much higher response rates, including responses like MLFS, give the patients the opportunity to go to transplant. And again, we're hoping to present data demonstrating revumenib bridging patients from responses into transplant and then potentially onto maintenance. And that's really the best opportunity to give patients a durable remission and outcome. So that's really the drive that you're seeing to combination.
Thank you.
Thanks, Gustav.
The next question is from Yigal Nochomovitz with Citi. You may now unmute yourself.
Hi, this is Joohwan Kim on for Yigal. Thanks for taking our questions. On the 20% sequential increase in new Revuforj patients, was that growth broad-based across newer accounts? Accounts are primarily concentrated within the established high-volume centers. Just wondering, are you seeing meaningful repeat prescribing among the newer accounts?
Thanks for the questions. First, the 20% quarter-over-quarter growth with accounts, is that kind of falling into this space?
Yeah, I think the exact question was, 20% increase in new patients, where are we seeing that from?
Right.
Where is it rising from? It is coming from all over. I mean, two-thirds of our business comes from what we will call tier 1, tier 2, and then the rest of the business comes from, we will say, smaller accounts, of which there are hundreds. We have had over 620 accounts prescribed to date. That is most of the tier 1s and tier 2s, about 90%. The rest are smaller community practices. That continues to grow. I think we had 8% growth in new accounts. The business is being spread, and that is how you want it. You want a large foundation of users treating a wide range of patients. That is how you build a big brand, and that is exactly what is happening today, and that will continue over time.
How would you characterize the repeat business?
High repeat business. We'll say this. I mean, the patients like this are, in general, challenging to treat. Even from early on in the launch, we've got a multifunction-type team, including nursing support care, to make sure clinicians and their entire staff know how to treat patients successfully with Revuforj. So, from the launch, and that continues today, from a customer and account that prescribes for the first time, they're going to get the care. So, the repeat rate is incredibly high, assuming they're seeing patients. Even smaller accounts will continue to use the drug on multiple occasions. As we know, Revuforj has been the standard of care in KMT2A and established itself in NPM1 patients to treat more patients on a continual basis.
Gotcha. If I could just ask one more quick one. On EVOLVE-2 and REVEAL, should we be thinking that the two studies complete enrollment on broadly similar timelines, or are you seeing that one is perhaps tracking ahead of the other?
Thanks for the final question. We haven't updated our guidance on either one of them, so I don't want to get into that at this point. Both are moving along well and on our schedule, so we feel encouraged.
Understood. Thank you very much.
Thank you.
The next question is from David Dai with UBS. Your line is now open.
Great. Thanks for taking my questions. So, there are encouraging new patient starts where there is about 20% quarter-over-quarter growth versus a decline in 2Q that you characterized as temporary. I mean, help us understand a little more around whether the improvement reflects the normalization of patient flow, better patient identification, broader account penetration, or shared gains from other menin inhibitors. And more importantly, what gives you confidence that this growth rate can remain positive over the next several quarters?
Thanks, David. So Steve, you want to tackle the new patient start questions?
Yeah, we can, David. Appreciate the question, and a question, right, reasonable to ask where the growth came from and why. I think, as we described last quarter, Q2 was a somewhat down quarter for the entire market, things happen. I mean, there is just variability quarter-to-quarter. There is not any one thing that drives this. I think what we are seeing in Q3 for us, encouraged by the 20% increase in new patient starts, there was growth in both KMT2A and NPM1. We continue to see the number of accounts expand. Formulary coverage is still holding. We obviously, we talk to clinicians and market research and gain insights. So we are encouraged overall by what we see in the business.
Just to reiterate, even the dynamic we see in the NPM1 patient moving from transplant, all the patients coming back, these are all good things that are based in the trust in the clinical profile. We talk about use. There are over 2,000 patients that have used the drug commercially, hundreds more in clinical trials. ASH is going to be great. There is so much good data coming. So in the forward, we are optimistic. We are not going to really comment on this quarter, but we gained a lot of steam in Q3, and that will continue for the rest of this year.
Right. I would just add that, look, remember, we have 80%-plus of this business, right? Relapse refractory is really ours, and we are continuing to build on that momentum. KMT2A, NPM1, we kind of have the dominant share across all age groups. So I think that is a very good place to be as we enter the last part of the year here.
Great. Thank you for taking my question.
Thanks, David.
The next question is from Salim Syed with Mizuho. Your line is now open.
Great. Thanks for the question, guys, and congrats on the progress. I guess one from us on the CFO transition, and thanks to Keith for all his help, and welcome to Erin. Keith, the press release was worded today as retiring. Just curious here, why you felt like First of all, is this the loose definition of retirement that we should be thinking about here, and you plan on doing something else? And why did you feel like right now was the right time to I guess it looks like it was your decision. Why was it the right time to make that transition out of Syndax and maybe to something else? Thank you.
Yeah. Salim, thanks. Thanks for the kind words and the question. Yeah, this was purely a personal decision that I made along with my family. Maybe the time was probably right a little earlier in the year. I care tremendously about this company, the patients that we treat, the teams that we've built, and wanted to ensure that the transition was as smooth as it could be, so there was to minimize any adverse impact on the business, on the team, on patients. So worked with the leadership team, the board, to find a great replacement. And yeah, this is not a retirement in a loose setting. So I'm looking forward to spending more time with my family, with my friends, pursuing some of my hobbies, doing some philanthropic work. So, yeah, it's been a good run.
I've been a CFO for 26 years, and yeah, just looking ahead to the future.
Okay. All right. Well, we wish you well, and congratulations, and thanks for the additional color, Keith. Thank you.
Thanks, Salim. Appreciate it.
Thanks, Salim.
The next question is from Andres Maldonado with H.C. Wainwright. Your line is now open.
Hi, everybody. Thanks for taking my questions, and Keith, I wish you the best as well.
Thank you.
Maybe circling back to some of the commentary on the transplantation eligibility. In the context of what you guys gave us today, the 40% in NPM1 versus the 50% in KMT2A, was curious on how much of that gap reflects age and fitness versus essentially cohort maturity? I guess, how realistically can that signal go? My second question is on combination use. Given the roughly, you stated today, that 40% of the use is in combinations, I guess, can you provide a little bit more color about which regimens are driving that outside of the usual suspects? Are they essentially how should we think about the breakdown of whether they're extending treatment duration or just primarily getting those patients to transplant? Thank you very much.
Great, Andres. Thanks for the question. In terms of what we're seeing with transplant, and where is essentially took your question as where is it really going here? The 40% for NPM1, with 50% of the patients returning for maintenance, 40% is a lot higher than we had expected. Could it get to 40%-50%? I expect it could, just given the momentum we're seeing. At 50% of those patients resuming, we expect maybe 60%-70% of those patients to resume maintenance. That is sort of how we see that. Again, it's more of a projection than a hard and fast rule. It's based on physician conversations and some research that we've done, and what we're seeing in the real world.
If you look at KMT2A, that's been creeping up over time, also much higher than we have seen in clinical trials now at 50% transplant rate, 60% resuming maintenance up from about 55% or 50% last quarter. It's really moving up on the patients returning for maintenance, which is quite encouraging. We've said that the transplant rate for KMT2A could probably go up to maybe 60%, probably not a lot higher. We expect 70% to 80% of those patients with KMT2A to come back on for maintenance. Again, thinking about how long they can stay on maintenance therapy and reflecting from what physicians have told us and what we've seen in some of our real-world work that we'll report on even at this upcoming meeting, you see that the desire is to treat them for one to two years in maintenance.
That would be a very good outcome for patients, keep them in remission for a long time, and hopefully move them forward. That is, I think, the paradigm that we're pursuing, again, with some estimates for what the rates could be. Nick, maybe I'll pass to you for the combination question.
Yeah, just a few additional comments on that, including in combination. One is, I think the drive to transplant, remember, in relapse refractory is really the best chance a patient can have of a durable remission. It's a little different from a consideration frontline. Once you've relapsed, you really want to get a patient to transplant if you can. We're hoping to update some data in the fourth quarter which looks at our patients that have gone on to get a transplant and looks at the role of revumenib as a sort of bridge to transplant. How do you get them there? What kind of response do you need to see? Including all of the contributors to overall response rate, which we know we have the highest overall response rate in the class.
That would include MLFS, and this makes these patients eligible for transplant, which I think is quite promising for patients. Combination use varies. I think what we see most commonly is Ven-Aza or single-agent venetoclax. Occasionally, other sorts of chemotherapy. Only rarely do we see combinations with targeted agents. They tend to be sequenced more, but occasionally it might be a combination. Then maintenance, of course, is really important. Again, I think we have the most mature and significant data really trying to elucidate how to optimally treat a patient with maintenance revumenib. We will be updating some data from a phase I we're doing with Dr. Ball, which I'm excited about, which looks at optimization of dose and managing patients. Then a variety of real-world data, again, optimizing patients with revumenib in the maintenance therapy.
As Michael said, physicians tend to want to keep them on if they can for one to two years. Again, we're hoping to update data on erasing MRD, which is really exciting, and I think that'll be the first data to be presented showing that. Then perhaps the last thing I would say is the data continues to mature. We are hearing from physicians now, if a patient's done really well and tolerating the drug well at two years, sometimes they don't even want to come off at two years. We are having discussions now with physicians who want to keep a patient on because they're just happy to be relapse-free out at two years after their transplant and doing well. That's also a trend we're beginning to see as the data matures.
Thank you.
The next question is from Jason Zemansky with Bank of America. Your line is now open.
Hi, this is Jackie Young for Jason. Congrats on the progress, and thanks for taking your question. You've talked about transplant creating a near-term headwind, but ultimately becoming a meaningful tailwind as the post-transplant population stacks. With the KMT2A restart rate now at 60% and NPM1m already at 50%, how should we think about the timing of that inflection? Is that something you expect to become a more meaningful driver of Revuforj growth over the course of 2027? Thanks.
Jackie, thanks for the question. I think you hit it on the head. Honestly, I think this is a really important phenomenon that takes some time to kind of play out. Basically, it's because you have patients who are going to transplant within, call it, three months of being put on Revuforj, and then they pause treatment for a number of months, call it two to four to five months, in some cases, maybe even more, and they pause treatment and then they resume. What that means is you're going to have the tailwind that kicks in quite a bit later, and you need time for the number of patients who drop for transplant to be kind of overcome by patients coming back, meaning in terms of revenue stack. Again, that takes time, and it takes time for both now NPM1 and KMT2A.
We haven't been kind of thinking about how NPM1 was part of this equation until recently. We saw the data that it's really very much the same, very similar paradigm to what we're seeing with KMT2A. That was a bit of news to us, but we think it will be ultimately a very good thing for patients as they come back on and can stay on treatment for a long time, as Nick had mentioned earlier. Yeah, so I think 2027 is where you'll see the greatest impact. We have started to see some of that, but we'll start to see more as it stacks in 2027.
Good. Thank you so much.
Thank you.
Our final question today is from Mayank Mamtani with B. Riley. Your line is now open.
Yes. Congrats on a strong execution quarter, and thanks for taking our question, and best wishes to Keith Goldan for his next chapter. Just a clarification question, and maybe if you could update us how maybe Q4 to date is progressing on the TRX versus NRX. Obviously, NRX did really well quarter-over-quarter. TRX is lagging a little bit, 20% versus 13%. Is there, again, anything you can comment on Q4, how that is kind of progressing would be helpful, but more sort of long term, just thinking about how, in a sustainable manner, we can see TRX accelerating. That would be just part one, commercial question. Then second on the, Nick, your comments on the newly diagnosed phase III program were very helpful.
Was just wondering if you could contextualize some of the paradigm, Ven-Aza, EFS, and MRD data we recently saw, and how do you think about MRD negative CR as a surrogate endpoint? Then just your expectation in fit versus unfit control arm for EVOLVE-2 also, and how do you see essentially maintenance being handled, given you're getting so much deep remission in the frontline setting across fit and unfit? Sorry, that was long-winded, but it would be great to hear your thoughts.
Anyway, thanks for the questions. Yes, the good news is I get the short question, which is the first one. What are we seeing in the fourth quarter? We are not going to comment on the fourth quarter. I will say, look, we feel good momentum coming out of third quarter, so we are very hopeful that the business will continue to really ramp from here. That is my answer. I am going to turn to the second set of questions from Nick.
Yes, great questions, and we can maybe talk a little bit more about the trials when we have presented our data at ASH, or at least the abstracts are open, and the relevance of those data to inform the phase III. What I would say is they give us a lot of confidence in the assumptions around the endpoints. Just to remind everybody very briefly, for the EVOLVE-2, we have two dual primary endpoints. One is CR, the other is overall survival. So those are relatively simple, and we will be updating data from both BEAT and SAVE that I think is very informative to those endpoints, and we feel very confident. The way we have designed those studies, I think, is quite strategically smart. Then for REVEAL, which is in fit patients eligible to receive intensive chemotherapy, again, we have dual primary endpoints.
One of them is quite stringent, which is looking at MRD-negative CR, but assessed in the bone marrow. Again, look for updates for our study 708, which is revumenib in combination with intensive chemotherapy that informed that study, and the relevance of those data for that study. Then the other dual primary endpoint in REVEAL is event-free survival, which again, takes a little time to mature, but is going to be the definitive endpoint, I would say, for potential approvals. So more on that to come, but the data are very helpful in ensuring we have got the studies designed and executed in the most efficient way we can, with the highest probability of success.
How are you handling maintenance crossover in these frontline studies, Nick?
Sorry, Mayank, can you repeat that?
The final part of that question was, how are you handling crossover and some of the maintenance settings, given you are getting deep remissions and some of them might be even going in transplant? I was just curious how the follow-ups are handled in the two studies.
Yeah, the studies do not allow for formal crossover for that reason. And recall, in REVEAL, the dual primary endpoint is event-free survival, which we are not anticipating to be unduly impacted by any subsequent therapies.
Thank you.
Thanks for the questions.
This concludes our question and answer session. I will now turn the floor over to Michael Metzger for any additional comments or closing remarks.
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 investor conferences in Q4 and at ASH. Before I say good evening, I want to thank Keith Goldan for all he's done for us. We wish you all the best in your retirement.
Thank you.
Have a good evening, everyone.
This concludes today's call. Thank you, and you may now disconnect.