Syndax Pharmaceuticals Inc Q3 FY2025 Earnings Call

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

Thank you, operator. Welcome, and thank you all for joining us today for a review of Syndax's Third Quarter 2025 Financial and Operating Results. I'm Sharon Klahre. 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. Also joining us on the call today for the question-and-answer session are Dr. Peter Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Strategy Officer. This call is accompanied by a slide deck that has been posted on the Investor page of the company's website. You can now turn to our forward-looking statements on Slide 2. Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent 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 3, 2025 only. A replay of this call will be available on the company's website, www.syndax.com, following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Thank you, Sharon. Good afternoon, and thank you all for joining us. The third quarter was another outstanding period for Syndax in terms of commercial and portfolio execution. The progress we made brings us closer to profitability and strengthens our leadership in menin inhibition, a promising new category where Syndax is uniquely positioned to excel in both relapsed/refractory and frontline settings. For our commercial results in the quarter, we reported $45.9 million in total revenue, reflecting strong 21% growth compared to the previous quarter. We are very encouraged by the launch metrics for both Revuforj and Niktimvo, two first-in-class medicines addressing significant patient needs. We have a solid influx of new patients starting treatment each quarter, along with a rising number remaining on therapy, laying a foundation for sustained long-term growth. Net revenue for Revuforj reached $32 million in the third quarter, up 12% from the previous quarter, despite about a third of patients temporarily pausing treatment for stem cell transplants. All indicators of demand remain robust, with approximately 25% growth in total prescriptions and new patient starts in the third quarter compared to the prior quarter. Revuforj has swiftly established itself as the standard of care for relapsed/refractory KMT2A, increasingly utilized early in treatment—with around 50% of usage in the second line. Many KMT2A patients are moving towards potentially curative stem cell transplants after Revuforj, which is a fantastic prospect for patients and their healthcare providers. The utilization of Revuforj in post-transplant maintenance continues to grow as physicians are reintroducing therapy for their patients. This trend is expected to become a significant growth driver in the upcoming quarter as more patients enter extended maintenance treatment, ultimately outpacing those who pause therapy for transplants. Recently, we made significant progress with another key growth factor for Revuforj. On September 18, Revuforj was incorporated into the NCCN Guidelines as a recommended treatment for relapsed/refractory NPM1 mutated AML prior to receiving subsequent FDA approval, underscoring the strength of our clinical data and physician enthusiasm. On October 24, we got FDA approval for Revuforj in relapsed/refractory NPM1 mutated AML, increasing our addressable patient population significantly. This approval also marks Revuforj as the first menin inhibitor FDA-approved for multiple acute leukemia subtypes in both adults and children aged one year and older. The wide reach of our indicated population reinforces the compelling efficacy and tolerability of Revuforj across various groups. Nick will provide further insights into the unique aspects of the Revuforj product profile during his review of our key abstracts at ASH this year. These data will enhance the growing body of efficacy evidence that sets Revuforj apart from other menin inhibitors. Our efforts to penetrate the NPM1 market are in full motion, and we are satisfied with our early progress in increasing awareness and generating demand among physicians treating NPM1 patients, who are already familiar with and trust Revuforj and Syndax. Within a week of approval, we’ve engaged with hundreds of physicians, and their feedback has been overwhelmingly positive. They are eager to use Revuforj as the first highly effective targeted therapy for relapsed/refractory NPM1. We are well-positioned for success with superior efficacy and a significant first-mover advantage over any competitors. Physician decisions in acute leukemia revolve around efficacy, and we possess differentiated efficacy data across multiple subtypes. Specifically, in relapsed/refractory NPM1, we have demonstrated unmatched results, including an approximately 50% overall response rate, a five-month median duration of complete responses, a 17% transplant rate, and a two-year median overall survival for responders. While complete response is a crucial regulatory measure, overall response rate is vital clinically. Higher rates enable clinicians to bring more patients into remission, enhancing the chances for eligible patients to undergo potentially curative stem cell transplants. Shifting to Niktimvo, in the second quarter following its launch, our partner Incyte reported $45.8 million in net revenue for Niktimvo, marking a robust 27% increase from the preceding quarter. In just the first eight months post-launch, Niktimvo is on track to annualize nearly $200 million and is performing similarly to Sanofi's REZUROCK, which surpassed $500 million in first-year U.S. net sales within three years in the same indication. Importantly, Niktimvo is profitable for Syndax, with our 50% share of its contributions totaling $13.9 million in the third quarter. As sales continue to grow, we anticipate that the share of net revenue we retain will increase significantly over time. We are advancing towards profitability, bolstered by the growing contributions from Revuforj and Niktimvo, a strong balance sheet, and a stable operating expense base over the next few years while fully funding our strategic priorities. Our key strategic efforts include expanding Revuforj and Niktimvo into frontline settings, which would unlock a combined market opportunity exceeding $10 billion. Enrollment in EVOLVE-2, the first pivotal frontline trial for a menin inhibitor, is underway. We have the appropriate strategy and partnerships to execute this trial successfully, aiming to be the first to introduce a menin inhibitor in frontline settings. For Niktimvo, two frontline trials are ongoing in combination with standard of care therapies that could revolutionize chronic GVHD treatment. Now, I will pass the call over to Steve to discuss our commercial progress in more detail. Steve?

Thank you, Michael. Starting with Revuforj on Slide 4. We're on track for a strong first year of sales with continued growth in KMT2A and a solid foundation in place for a successful launch into NPM1 and our future expansion into the frontline setting. In the first ten months of sales, we've generated nearly $90 million in Revuforj net revenue, exceeding by a wide margin the launch benchmark set by other AML therapies. These impressive results reflect the rapid adoption of Revuforj as the standard of care in relapsed/refractory KMT2A and physicians' positive experience with the drug. Sales of Revuforj were strong in the third quarter with $32 million in net revenue, up from $28.6 million in the prior quarter. Importantly, key demand indicators increased even more significantly with total prescription and new patient starts for the quarter both increasing approximately 25% over the prior quarter. This robust increase in demand speaks to Revuforj's compelling product profile and the strong and durable business that we are building. The delta between demand and net revenue growth this quarter was due to variability in gross to net and channel inventory as you often see period-to-period, especially in the first year of the launch. Since launch in late 2024 through the end of September of this year, approximately 2,200 prescriptions have been written for 750 patients, with an estimated 90% of usage in KMT2A. With this momentum, we remain on track to treat 1,000 KMT2A patients by year's end or more. This would represent 50% penetration of the annual 2,000-patient KMT2A incidents within the first year of launch, and that is a fantastic result. The use of Revuforj continues to migrate to earlier lines of therapy, with claims data showing approximately 70% of usage concentrated in the second and third line, with 50% coming from the second line or first relapse patients alone. Claims data is also showing significant combination use, with one-third of patients receiving Revuforj in combination with another standard of care therapy, venetoclax being the most common. This trend highlights physicians' comfort with the Revuforj profile and the potential for average treatment durations to extend over time as treatment patterns mature. Consistent with last quarter, an estimated one-third of KMT2A patients treated with Revuforj have proceeded to a stem cell transplant, and we continue to see patients being put back on Revuforj by their physicians after a three- to four-month pause for engraftment. We estimate that 35% to 40% of transplant patients have restarted Revuforj, with that percentage expected to build over time as more patients clear the engraftment period and physicians gain more experience using Revuforj post-transplant. As we've seen in our clinical trial and expanded access program experience, we expect patients could stay on therapy for one to two years post-transplant, given the high risk of relapse and the favorable tolerability of Revuforj. As Revuforj is used earlier in the treatment paradigm, and more patients restart after transplant, we expect this will translate into a significant increase in the overall average duration of therapy. Based on our experience to date, we anticipate the average duration of therapy for KMT2A patients will be four to six months this year and six to 12 months in 2026 as treatment patterns further mature. Let's turn to NPM1, the next important growth driver for Revuforj. As shown on Slide 5, the second indication approved for Revuforj expands our annual total addressable U.S. population from approximately 2,000 to 6,500 incident patients across both genetic subtypes in the relapsed/refractory setting, a $2 billion-plus market opportunity. Moving to Slide 6. Our promotional expansion into NPM1 began quickly once we received approval on Friday, October 24, with broad communication outreach to all relevant treatment centers and healthcare practitioners. The very next day, we had members of our field team trained and promoting the new indication at an oncology conference. Our engagement with HCPs has only expanded from there. We are pleased with the early progress we have made driving awareness of the expanded indication and generating demand in NPM1. Physicians are enthusiastic to have Revuforj as a new effective option for their NPM1 patients. Our success in NPM1 is going to be driven by two main factors: First, the breadth and strength of the Revuforj efficacy data and the overall product profile. With unmatched efficacy data across multiple patient subtypes, we are positioned to serve patients and secure dominant market share, given that physicians consider efficacy the most important factor driving their prescribing decisions. We are also the only company now and for the foreseeable future with a menin inhibitor that is FDA approved for multiple acute leukemia subtypes in patients one year and older. The ability to use one efficacious and generally well-tolerated drug across 40% to 45% of patients with AML is a huge benefit to practitioners and payers. Second, we have a solid commercial foundation that we're leveraging, including a large prescriber base that has already seen excellent clinical results with Revuforj and has experienced how easy we've made it for their patients to gain access to the drug. Physicians have already treated well over 1,000 patients with Revuforj across nearly one year of commercial use, clinical trials, and our EAP. From launch through the end of September, 70% of Tier 1 and Tier 2 accounts in the U.S. have started using Revuforj on a regular basis. Physicians tell us it typically takes two or three patients to develop loyalty and habit with a new oncology medicine, and most of the major centers have already built up that comfort and muscle memory with Revuforj. Beyond the largest institutions, adoption is also increasing across all other sizes of accounts, including community practices. Our broad and growing prescriber base gives us a significant competitive advantage as we expand into NPM1. The positive experience accounts have had with Revuforj reflects the world-class commercial organization and infrastructure we have built to deliver to patients. We have an efficient limited distribution model with an average time from prescription to first fill of less than four days. Our highly experienced customer engagement team has long-standing relationships with key prescribers and accounts. Formulary coverage for KMT2A is already in place for 97% of covered lives and is expected to build rapidly for NPM1. While it builds, we expect the reimbursement rate to be high given the NCCN Guideline listing for NPM1 and the existing KMT2A coverage. We have everything we need for a successful expansion into NPM1 and look forward to providing further updates as this exciting launch progresses. Turning to Niktimvo on Slide 7. We saw robust Niktimvo growth in the third quarter with $45.8 million in net revenue, up 27% from the prior quarter. We continue to receive excellent feedback from HCPs on the rapid and durable improvements they are observing with Niktimvo across some of the most difficult-to-treat organs associated with chronic GVHD. We are steadily adding new patients and patients are staying on therapy. From the start of the launch through the end of the third quarter, 8,500 infusions have been administered to 1,100 patients. Usage has been mostly in the fourth line, but it is growing in the third line, with the recent decrease in REZUROCK sales corresponding with increased adoption of Niktimvo. Of the patients who started Niktimvo in Q1, approximately 80% remain on therapy today. The breadth and depth of prescribing continue to grow with 90% of bone marrow transplant centers in the U.S. prescribing Niktimvo, with all centers placing repeat orders year-to-date. While we've made excellent progress in the first eight months, we still have significant room to continue growing given the scale of the unmet need, with approximately 6,500 patients in the U.S. requiring three or more lines of therapy, representing a $2 billion market opportunity, as shown on Slide 8. I'll close by saying that I'm thrilled by the progress we have made with Revuforj and Niktimvo. Both medicines are delivering for patients and on blockbuster trajectories. Achieving success as a commercial organization takes great products, great plans, and great execution, and we have all three, positioning Syndax for sustained growth for years to come. With that, I'll hand the call over to Nick to discuss our upcoming data presentations at ASH. Nick?

It's a pleasure to be on the call today. Thank you, Steve, and to discuss the strong presence Syndax will have at ASH with 23 abstracts accepted for presentation, including 6 oral presentations, highlighting our scientific leadership in menin inhibition and CSF-1R inhibition. Starting with Revuforj or revumenib. Collectively, the abstracts highlight the remarkable activity and tolerability of revumenib in multiple genetic subtypes, both as a monotherapy and in combination with standard of care therapies across the acute leukemia treatment continuum. Slide 9 summarizes the first real-world evidence for menin inhibitor. Data from the first 18 patients treated commercially with Revuforj at Moffitt Cancer Center show favorable tolerability and excellent clinical activity across multiple genetic subtypes and settings. Patients with NPM1, KMT2A and NUP98 acute leukemias are included in the data set. Fifteen patients received Revuforj in the relapsed/refractory setting, two in frontline, and one after stem cell transplant without prior Revuforj treatment. Notably, nearly 80% of the patients received Revuforj in combination with standard of care regimens, most commonly venetoclax plus HMA. At the time of the abstract data cutoff, median follow-up was relatively short at about four months. Sixteen patients were efficacy evaluable. Among 14 patients treated for morphological marrow disease relapse, 79% achieved an overall response. Rates of MRD negativity by flow cytometry were high at 86% and 67% for KMT2A and NPM1 responders, respectively. Four patients or 29% of the population treated for morphological disease proceeded to a stem cell transplant. Three patients received Revuforj as maintenance post-transplant, including two who resumed Revuforj post-transplant and who started post-transplant without prior Revuforj treatment. It's also noteworthy that there were two additional patients who were treated with Revuforj NPM1 MRD positivity, with one of the patients achieving MRD negativity at the data cutoff. The potential use of revumenib as an MRD eraser in HOX/MEIS-driven tumors is an area of high clinical interest with multiple ongoing studies exploring this area. Importantly, Revuforj was well tolerated in this real-world cohort, consistent with what we have observed among more than 1,000 patients treated across our broader clinical trial compassionate use and commercial experience. There was a low rate of revumenib dose reductions, and no AEs led to revumenib discontinuation. DS and QTC were well managed with no events of either above Grade 3. The first real-world data set provides important insight into the breadth of Revuforj usage we are observing at leading academic institutions like Moffitt. The use in KMT2A, NPM1, and NUP98 underscores the clinical value of the data we have presented, showing activity in multiple genetic subtypes, one of the several differentiating features of the revumenib profile. The high rate of combination therapy observed highlights physicians' comfort with revumenib's safety profile and their desire to combine therapies with the hope of achieving deeper and more durable responses. We look forward to the presentation of longer-term follow-up data from Moffitt at ASH. This presentation will be the first in a series of real-world data sets we will be collecting and presenting in partnership with leading physicians and centers. Turning to Slide 10 and the frontline setting. We are pleased to share data from the first 17 patients enrolled in the newly diagnosed cohort of the SAVE trial. This trial is evaluating revumenib in combination with venetoclax and decitabine/cedazuridine in the relapsed/refractory and frontline settings. These new data show the combination was well tolerated in newly diagnosed patients with high rates of complete remission or CR and MRD negativity. Among newly diagnosed patients with NPM1 or KMT2A, 88% of evaluable patients achieved a CR. 100% of patients with CR were MRD negative by flow cytometry. Five patients or 29% proceeded to transplant. Two of these patients had resumed revumenib as post-transplant maintenance at the time of the data cutoff. At a median follow-up of six months, median OS and EFS were not reached. The combination was well tolerated. DS and QTC were well managed with no events of QTC above Grade 2 and no events of DS above Grade 3. This is an important data set that builds on the encouraging results observed in the BEAT-AML trial of revumenib with venetoclax and azacitidine in newly diagnosed patients with AML. The concordance of the results from two different studies and different centers bolsters our confidence in the potential for revumenib in combination with low-intensity therapy to transform the treatment paradigm for newly diagnosed NPM1 or KMT2A AML. To realize the full therapeutic potential of Revuforj, we are laser-focused on advancing our frontline trials, including the pivotal EVOLVE-2 trial of revumenib with ven/aza that was initiated in collaboration with HOVON in the first quarter of 2025, the first pivotal trial of a menin inhibitor to start enrolling in the frontline setting. Moving now to Slide 11 and preliminary Phase I data supporting revumenib in combination with intensive chemotherapy or 7+3 in newly diagnosed patients with NPM1 or KMT2A AML. Data from two ongoing trials will be presented at ASH, including one led by the National Cancer Institute, or NCI, and one led by Syndax. Collectively, the early data from these trials show the tolerability of revumenib in combination with 7+3, along with high rates of CR, MRD negativity, transplant, and rapid count recovery. Both trials evaluated two dose levels of revumenib in combination with 7+3 induction and cytarabine consolidation. Dose level 1 was revumenib at 110 or 220 milligrams every 12 hours with or without strong CYP3A4 inhibitor, respectively. Dose level 2 was at the FDA-approved monotherapy dose. No maximum tolerated dose has been identified and the adverse events reported were consistent with the known AE profile of intensive chemotherapy and revumenib. In the NCI trial, one investigator-assessed dose-limiting toxicity or DLT was reported at dose level 2. This was one Grade 5 event of typhlitis or severe inflammation of the intestine, a complication that is known to occur in patients receiving intensive chemotherapy. There were no reports of DS or QTC prolongation of any grade. The NCI investigators concluded that revumenib appears to be well tolerated both with 7+3 induction and consolidation. In the Syndax study, one DLT of Grade 3 QTc prolongation was reported at dose level 1. This patient discontinued revumenib during the first cycle. Notably, at the end of the first cycle, the patient had achieved a MRD-negative CR and went on to receive a stem cell transplant. Turning to the promising clinical activity observed among nine efficacy evaluable NPM1 and KMT2A patients in the NCI trial at the dose level one or two at the time of the abstract data cutoff, 89% achieved a CR, and 44% proceeded to transplant following treatment with revumenib. The median time to full count recovery, including both neutrophils and platelets was 25.5 days among patients with CR. Among seven efficacy evaluable KMT2A patients in the Syndax trial at the time of the data cutoff, 100% achieved a CR, and the MRD negativity rate was 100% among evaluable patients, 57% proceeded to transplant. At ASH, data from additional patients and follow-up will be presented from both trials. Seeing positive early data from these two trials is very encouraging as we near the initiation of the registration-directed REVEAL program, which will evaluate revumenib in combination with intensive chemotherapy in newly diagnosed fit patients with NPM1 or KMT22A. We remain on track to initiate REVEAL by the end of 2025 and look forward to providing further updates in due course. Turning to Slide 12. This abstract provides insights into the growing usage of revumenib we are observing in the post-transplant setting. In a retrospective review of ten pediatric patients with KMT2A or NUP98r acute leukemia who received revumenib maintenance post-transplant at MD Anderson, revumenib was well tolerated with promising early efficacy. Patients received a median of two cycles of revumenib prior to transplant, and revumenib was initiated at a median of 111 days or roughly three to four months post-transplant, consistent with what we have observed in other data sets. The study planned for continuation of revumenib post-transplant for up to one year. Patients had completed a median of 11 cycles post-transplant at the time of the data cutoff. One patient continued for two years due to parental preference. This highlights the tolerability of Revuforj and reinforces prior feedback we have received from patients and families on the strong desire to stay on therapy that induced remission. At the last follow-up, all ten patients were alive with no relapses, yielding an estimated one-year event-free survival of 100%. This is very encouraging results in a population with a high risk of relapse within the first year. The use of revumenib in the post-transplant setting is an area of high clinical interest. In addition to the abstract just discussed, investigators from a different study will present a trial in progress poster describing a Phase I trial evaluating the safety and preliminary efficacy of revumenib as post-transplant maintenance in adult and pediatric patients with NPM1 or KMT2A. This trial, which is actively recruiting at City of Hope and Dana-Farber Cancer Institute, is planning to continue revumenib for two years post-transplant. Turning now to axatilimab on Slide 13. I will briefly highlight three axatilimab abstracts that underscore the potential for long-term benefit in recurrent refractory chronic GVHD and the feasibility of combining ruxolitinib in newly diagnosed chronic GVHD. The first abstract shows that 33 of the 239 patients in the pivotal AGAVE-201 trial of axatilimab were still on therapy as of March 2025, with a median of 2.8 years on axatilimab. Long-term data show a continued tolerable safety profile. The second abstract reports the safety and feasibility of axatilimab in patients who had a response at the FDA-approved dose of 0.3 milligrams per kilogram every two weeks and then transitioned to a double dose every four weeks. Among the 19 patients who switched, the four-week dosing was well tolerated with a median of 1.7 years on therapy after the dosing change. The third abstract reports interim safety data from 44 patients enrolled in the ongoing Phase II trial of axatilimab with ruxolitinib in newly diagnosed chronic GVHD. The data showed the combination was well tolerated, paving the way for the further development of this potentially steroid-sparing regimen. Importantly, this is one of two ongoing trials that have the potential to expand axatilimab into the frontline setting in combination with standard of care therapies. In summary, this year's ASH will be another exciting meeting for Syndax. After watching the clinical community's enthusiasm for revumenib and axatilimab grow over the year, it's a pleasure to have the opportunity to share the next wave of data that will help drive forward the next phase of progress for patients. And with that, I will hand over the call to Keith to discuss our financials.

Thanks, Nick. Earlier this afternoon, we reported detailed third quarter 2025 financial results. I will touch on a few key points on Slide 14. For the third quarter of 2025, we reported Revuforj net revenue of $32 million. Quarter-over-quarter sales growth was driven by demand as inventory levels remained at 2 to 3 weeks. While prescription demand increased 25% quarter-over-quarter, net sales grew 12% over the prior quarter. The primary reason for this delta was an increase in Revuforj's gross to net adjustments in the third quarter versus Q2, while still within the 20% to 25% guidance range we previously provided. The increase was due to higher proportion of 340B business in the quarter as well as higher exposure to Medicare and Medicaid, all of which mandate statutory discounts. There was also a slight drawdown of inventory in the channel this quarter, while still within the 2- to 3-week range that we previously guided. Looking ahead, we expect sales growth to meaningfully accelerate over the coming quarters with the approval in NPM1 and an increasing average duration of therapy in KMT2A as more patients receive Revuforj as long-term maintenance therapy post-transplant. Turning to Niktimvo. Syndax reported $13.9 million in collaboration revenue after deducting the cost of sales and commercial expenses. Importantly, Niktimvo continues to be a positive cash flow contributor to Syndax. We continue to expect the Niktimvo margin contribution, defined as collaboration revenue recorded by Syndax as a percentage of Niktimvo net sales to be in the 25% to 30% range in the near term and increase longer term as sales grow and the partnership leverages a largely fixed expense base. We expect continued robust growth given GVHD is a chronic disease where there is a high response rate to Niktimvo and the average patient will likely remain on therapy for years. Turning to the balance sheet. We continue to maintain a strong financial position with $456 million in cash, equivalents, and short- and long-term investments as of September 30. As I've said in the past and reiterate today, we expect Syndax will reach profitability with current funds on hand. In fact, my confidence is higher today given that both drugs are outperforming our original forecasts. We are confident we can execute commercially, and also deliver on our integrated clinical development plans for both drugs while keeping operating expenses at today's levels. Our cash, combined with increasing Revuforj and Niktimvo cash flow contributions alongside an expected fixed expense base will drive our path to profitability. Michael?

Thank you, Keith. Turning to Slide 15. Syndax has never been in a stronger position than we are today. We have two first and best-in-class therapies on blockbuster trajectories with plenty of room for growth in the front line and beyond. We have an outstanding team that is consistently executing at the highest level, culminating in three FDA approvals and launches within roughly 1 year, a remarkable achievement. With two exceptional product launches underway, a strong balance sheet, and stable expense outlook, we are on the road to profitability and fulfilling our mission as a company. I would like to close by thanking everyone who has made it possible for us to make a major impact for patients, especially our talented Syndax employees and long-term investors. With that, I would like to open the call for questions.

The first question is from Anupam Rama with JPMorgan.

This is Priyanka on for Anupam. Can you review how Revuforj's place in lines of therapy has evolved in the commercial setting during the launch? And how do you think this will translate for the NPM1 setting? Would physicians with experience with Revuforj be more willing to use it in earlier lines of therapy?

Yes. Thanks, Priyanka, for the question. I'll take that. So, look, lines of therapy, I think the question is relating to how is it being used in clinical practice. For KMT2A, we have said that about 70% of our business is second or third line, so that's first relapse or second relapse. That's a stark change from what we've seen in our clinical trial where third and fourth line was the average patient. And so, what the meaning of that is, is that it enables patients to be treated earlier. They tend to do better, stay on treatment longer. We've seen an uptick in the amount of patients going to transplant as a result. We've seen in our clinical trial we saw 25% of patients go to transplant. In our commercial experience, we've seen about one-third go to transplant. So, we've actually seen quite a shift and that we think will manifest in patients staying on drug longer over time in KMT2A. So that's been very meaningful. And we expect with NPM1, these patients are getting to transplant as well. We're also seeing high rates of response. About half of the patients get to response. We do expect them to be treated earlier and earlier in the treatment journey. And as we've talked about, patients are also being treated in combination. So that will drive patients to earlier utilization within their journey. So, this is, I think, a trend that will continue not just for KMT2A, but for NPM1 and ultimately should lead to better utilization and longer utilization for patients.

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

You spoke about a six- to twelve-month range for duration of therapy in 2026. Could you help us think about the key factors that you're looking to understand in order to narrow that range? And when could that start to be reflected in the revenue trajectory?

Thank you, Corinne. That's an excellent question. In 2025, we noted that new patients typically stay on therapy for four to six months, which reflects both new patient starts and some patients returning for maintenance therapy after transplant. However, the real impact on therapy duration will be seen in 2026, as more patients come back from transplant to receive maintenance. We're also anticipating the launch with NPM1, leading to more patients being treated, some of whom will ultimately go to transplant. The patient mix will vary, particularly between KMT2A and NPM1; KMT2A tends to have a longer treatment duration since more patients in that category will go to transplant compared to NPM1. Consequently, we expect more patients to be on treatment for NPM1, although they may have a slightly shorter duration due to fewer patients going to transplant. The interaction between these two populations is what we believe will contribute to achieving a therapy duration of six to twelve months in the second year.

Your next question will come from Brad Canino with Guggenheim.

Nice commercial momentum on the quarter. First question for you. Have you looked at all where the maintenance restart rate is for the patients who started Revuforj during the first few months of launch? Because obviously, the 35% to 40% you're reporting is weighed down by the bolus of recent patients getting transplants, but not yet undergoing the ability to get maintenance. So, were you able to do a longitudinal analysis at all to understand where that restart rate number can grow to?

Excellent question, Brad. I think we've seen some progress this quarter in the restart rate, where we saw last quarter about one-third of patients restarting maintenance therapy. Now it's up to about 35%, 40%. We do believe that will grow over time. Additional patients, steady flow. We've seen this quarter going to transplant, again, not fully offset by the patients coming back. We do think that that will build in the next quarter and the quarters beyond. We don't have an upper limit of what percentage of patients will come back, although what we've heard from physicians is that they're very keen to put them back on therapy. And so, what we've heard is as many as 80%, 90%, they've given figures that they would say almost all their patients. Hard to estimate what the upper limit is of what percentage of patients will come back. It is impacted by other factors that are beyond the control of physicians if a patient has extenuating circumstances. But I think the inclination is to bring them back and put them on therapy. So, we'll just have to wait and see how that manifests. But it's a good sign that even now we're starting to see more patients come back on.

Your next question will come from Clara Dong with Jefferies.

So, as we think about the relationship between prescription growth and revenue growth, could you provide some perspective in terms of how revenue per prescription might evolve as the patient mix shifts from predominantly KMT2A in the third quarter to include more NPM1 patients going forward?

Yes. Keith, do you want to take that question?

Yes, Clara, thanks for the question. We really don't expect much of a change in terms of average revenue per prescription as more and more NPM1 patients start to make their way into our prescribing base.

Your next question will come from Peter Lawson with Barclays.

Just on the delta between quarter-over-quarter growth results versus the Rx rate. And is there any way to break down that gap between gross to net versus inventory timing that we should be thinking about or any changes that we should be thinking about going forward? And then I've got a question just on if there's been any friction again NPM1 authorizations and payer access.

Peter, thanks for the question regarding quarter-over-quarter growth and the breakdown between what we're seeing in those metrics. But Keith, why don't you take that question?

Yes, Peter, thank you. I'd start off by saying that generally, when you see a disconnect in a quarterly result between net revenue and prescription growth as is often the case, especially in launches, there's generally two factors that play into that, and it's generally gross differences in gross to net and differences in inventory stocking. And as I said, both can fluctuate quarter-to-quarter. In this period, as I said in my prepared remarks, the delta was primarily driven by higher gross to net adjustments. I want to emphasize it's still within the range we provided. So a very tight range of 20% to 25%, but we did have slightly higher 340B chargebacks and slightly higher Medicaid to Medicare utilization. As I said, both remain within the guidance range as does inventory. The two to three weeks, which is very typical of specialty launches, rare disease launches using the type of distribution network that we do. But we did see a slight drawdown in inventory, which those two factors combined to explain the disconnect between prescription growth of 25% and revenue growth of 12%.

Yes. And I would just add that, again, just to remind you, Peter, that we had about one-third of revenue go away, if you will, for patients who were going to transplant. And we had an offset of only about 35% to 40% of those patients coming back. So that will build over time, but that was, of course, is a factor in what could have been a different quarter from a top line perspective.

And I think the other part of Peter's question was just on the payer side.

Yes.

Payer access and formulary coverage for Revuforj have been excellent since its launch. By the fifth month, we achieved 97% formulary coverage, allowing seamless access for commercial Part D and Medicaid patients. There have been some off-label prescriptions outside of KMT2A, which we estimate to be around 10% since launch, and we expect this usage to increase with the indication. We have not encountered significant pushback from payers, even prior to the NPM1 indication. Following the publication in May, the NCCN listing in September has been crucial for payer coverage. This is what payers require for product coverage, and having an official indication will enhance that. Our payer team has been engaging with payers since we submitted the sNDA earlier this year, and we anticipate quick growth in coverage. In the meantime, as coverage expands, claims will be processed and reimbursed, ensuring that patients continue to have open access to Revuforj until the coverage is made permanent.

Your next question will come from Ellen Horste with TD Cowen.

Congrats on the quarter and all the exciting abstracts. Just wondering a couple of things about the NPM1 launch. One, if you noticed any modest uptick in the final days of Q3 where you did have that inclusion in NCCN Guidelines? And then more broadly, wondering how we should think about the launch trajectory in the NPM1 population in terms of market penetration relative to the launch in the KMT2A market, given that, as you said, it's a larger population, but it's likely to face some competition. Any thoughts there would be helpful.

Yes, thanks for the question. I'll begin with some comments about the quarter and then hand it over to Steve to discuss the launch trajectory. So, we had a strong start to the quarter, and healthcare professionals are excited. As you can imagine, awareness is quite high. We're seeing an increase in prescriptions, and accounts are ordering and expanding. The outlook for the future is positive. We had guidelines released in late September, which didn't significantly impact the quarter but sets us up well for the upcoming quarter and approval in October. This combination positions our launch very favorably. We expect a solid Q4, which should contribute significantly to our KMT2A business. The factors driving our KMT2A business include steady new patient starts and patients returning to maintenance therapy, which will lead to growth. So, we're anticipating a good Q4. Now, I'll turn it over to Steve to discuss the launch trajectory in NPM1.

Yes. Just to add on to Michael's comments. I mean, awareness and excitement around the new indication is incredibly high. Our field force was trained within days, and we were talking to customers the day after approval, I think I mentioned in my prior comments. We're excited about the launch. I know physicians are as well. There's three main drivers as we think about this. We'll see if and when, there is competition, we prepare as though there is, which is why we operate at a very high level and execute as best as we can. First is product profile. We think we have an unsurpassed profile, really best-in-class, two indications covering nearly half of the population, adults and peds, AML, ALL. We've talked about this. Efficacy is the most important attribute for any cancer oncology heme or indication. And we believe we have the best data, and that's what physicians tell us. The drug is well tolerated, range of doses. Physicians have proven that they can use it in KMT2A very widely as well as in NPM1, and they'll have more experience doing that. Second piece is really just around relationships and ability to execute. We've been in the market for selling for almost a year, but our field team was in place even six months in advance of that. We've got great relationships. The experience that physicians have had has been excellent around the drug. We've talked about 1,000 patients treated to date. We'll be over 1,000 patients treated commercially. That means a lot. We've got a growing account base and not just large accounts, it's been medium-sized accounts as well as community practices, really showing unmet need and also how easy it is to use the drug. And that experience accounts have had with Revuforj reflects the world-class commercial organization and infrastructure we have built to deliver to patients. We have an efficient limited distribution model with an average time from prescription to first fill of less than four days. Our highly experienced customer engagement team has long-standing relationships with key prescribers and accounts. Formulary coverage for KMT2A is already in place for 97% of covered lives and is expected to build rapidly for NPM1. While it builds, we expect the reimbursement rate to be high given the NCCN Guideline listing for NPM1 and the existing KMT2A coverage. We have everything we need for a successful expansion into NPM1 and look forward to providing further updates as this exciting launch progresses. Turning to Niktimvo on Slide 7. We saw robust Niktimvo growth in the third quarter with $45.8 million in net revenue, up 27% from the prior quarter. We continue to receive excellent feedback from HCPs on the rapid and durable improvements they are observing with Niktimvo across some of the most difficult-to-treat organs associated with chronic GVHD. We are steadily adding new patients and patients are staying on therapy. From the start of the launch through the end of the third quarter, 8,500 infusions have been administered to 1,100 patients. Usage has been mostly in the fourth line, but it is growing in the third line, with the recent decrease in REZUROCK sales corresponding with increased adoption of Niktimvo. Of the patients who started Niktimvo in Q1, approximately 80% remain on therapy today. The breadth and depth of prescribing continue to grow with 90% of bone marrow transplant centers in the U.S. prescribing Niktimvo, with all centers placing repeat orders year-to-date. While we've made excellent progress in the first eight months, we still have significant room to continue growing given the scale of the unmet need with approximately 6,500 patients in the U.S. requiring three or more lines of therapy, representing a $2 billion market opportunity, as shown on Slide 8. I'll close by saying that I'm thrilled by the progress we have made with Revuforj and Niktimvo. Both medicines are delivering for patients and on blockbuster trajectories. Achieving success as a commercial organization takes great products, great plans and great execution, and we have all three, positioning Syndax for sustained growth for years to come.

With that, I'll hand the call over to Nick to discuss our upcoming data presentations at ASH. Nick?

It's a pleasure to be on the call today. Thank you, Steve, and to discuss the strong presence Syndax will have at ASH with 23 abstracts accepted for presentation, including 6 oral presentations, highlighting our scientific leadership in menin inhibition and CSF-1R inhibition. Starting with Revuforj or revumenib. Collectively, the abstracts highlight the remarkable activity and tolerability of revumenib in multiple genetic subtypes, both as a monotherapy and in combination with standard of care therapies across the acute leukemia treatment continuum. Slide 9 summarizes the first real-world evidence for menin inhibitor. Data from the first 18 patients treated commercially with Revuforj at Moffitt Cancer Center show favorable tolerability and excellent clinical activity across multiple genetic subtypes and settings. Patients with NPM1, KMT2A and NUP98 acute leukemias are included in the data set. 15 patients received Revuforj in the relapsed/refractory setting, 2 in frontline and 1 after stem cell transplant without prior Revuforj treatment. Notably, nearly 80% of the patients received Revuforj in combination with standard of care regimens, most commonly venetoclax plus HMA. At the time of the abstract data cutoff, median follow-up was relatively short at about four months. 16 patients were efficacy evaluable. Among 14 patients treated for morphological marrow disease relapse, 79% achieved an overall response. Rates of MRD negativity by flow cytometry were high at 86% and 67% for KMT2A and NPM1 responders, respectively. 4 patients or 29% of the population treated for morphological disease proceeded to a stem cell transplant. 3 patients received Revuforj as maintenance post-transplant, including 2 who resumed Revuforj post-transplant and who started post-transplant without prior Revuforj treatment. It's also noteworthy that there were 2 additional patients who were treated with Revuforj NPM1 MRD positivity with one of the patients achieving MRD negativity at the data cutoff. The potential use of revumenib as an MRD eraser in HOX/MEIS-driven tumors is an area of high clinical interest with multiple ongoing studies exploring this area.