SNDX - NASDAQ

Good day, everyone, and welcome to the Syndax Third Quarter 2025 Earnings Conference Call. Today's call is being recorded. [Operator Instructions] 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. Starting with Slide 3. The third quarter was another outstanding period of commercial and portfolio execution for Syndax. Importantly, the progress we made advances us on the road to profitability and furthers our leadership position in menin inhibition, an exciting new category that Syndax is uniquely positioned to lead across the relapsed/refractory and frontline setting. Starting with our commercial results for the quarter. We reported $45.9 million in total revenue for the third quarter, representing strong 21% growth over the prior quarter. We are very encouraged by the launch metrics for both Revuforj and Niktimvo, 2 first and best-in-class medicines that are addressing major unmet patient needs. With both medicines, a robust base of new patients are starting each quarter and a growing number are continuing on therapy, building a foundation for sustained long-term growth. Net revenue for Revuforj was $32 million in the third quarter, up 12% from the prior quarter, even with approximately 1/3 of patients temporarily pausing treatment to receive a stem cell transplant. Importantly, all indicators of demand remain strong and with approximately 25% growth in total prescriptions and new patient starts in the third quarter compared to the prior quarter. Revuforj has become -- rapidly become the standard of care for relapsed/refractory KMT2A and is widely being used early in the treatment paradigm with approximately 50% of usage in the second line. A growing number of KMT2A patients are proceeding to a potentially curative stem cell transplant after receiving Revuforj, a fantastic outcome for patients and clinicians. The use of Revuforj in the post-transplant maintenance setting also continues to build as physicians put their patients back on therapy. This dynamic will become an important growth driver in the fourth quarter and beyond as the number of patients receiving extended maintenance treatment begins to meaningfully offset and then exceed the number who paused therapy each quarter to receive a transplant. In the third quarter and recent weeks, we have made major strides advancing another important Revuforj growth driver. On September 18, Revuforj was added to the NCCN Guidelines as a recommended treatment option for relapsed/refractory NPM1 mutated AML ahead of the subsequent FDA approval, which speaks to the strength of our clinical data and physicians' enthusiasm for Revuforj. On October 24, we received FDA approval for Revuforj in relapsed/refractory NPM1 mutated AML, tripling the size of our addressable patient population. This approval makes Revuforj the first and only menin inhibitor that is FDA approved for multiple acute leukemia subtypes in adult and children 1 year of age or older. The breadth of our indicated population highlights the compelling and consistent efficacy and tolerability of Revuforj across different patient populations. Nick will unpack the unique aspects of the Revuforj product profile when he reviews the key abstracts we will have this year at ASH. These data sets will add to the growing body of efficacy data that differentiate Revuforj from other menin inhibitors. Our expansion into NPM1 is in full swing, and we are pleased with our early progress driving awareness of the new indication and generating demand among physicians who treat NPM1 patients. Importantly, these are the same physicians who treat KMT2A patients and have already built familiarity and trust with Revuforj and Syndax. In the 1 week since approval, we have already engaged with hundreds of physicians and feedback has been very positive. They are enthusiastic to have Revuforj as the first highly efficacious targeted therapy indicated for relapsed/refractory NPM1. We are well positioned for success with best-in-class efficacy and at least a 1-year first-mover advantage over any other company. Physician decision-making is driven by efficacy in acute leukemia, and we have differentiated efficacy data in multiple acute leukemia subtypes. In relapsed/refractory NPM1 specifically, we have shown unmatched data, including an approximately 50% overall response rate, 5-month median duration of CR/CRh, 17% transplant rate and a 2-year median overall survival observed among responders. While CR/CRh is an important regulatory endpoint, ORR is of utmost importance from a clinical standpoint. A higher overall response rate gives clinicians the ability to bring more patients into remission and the best chance of bringing their eligible patients to a potentially curative stem cell transplant. Moving to Niktimvo. In the second quarter of launch, our partner, Incyte, reported $45.8 million in Niktimvo net revenue, a robust 27% increase over the prior quarter. Within just the first 8 months of launch, Niktimvo is annualizing at nearly $200 million and tracking in line with first year sales of Sanofi's RE

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 10 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 1/3 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 1/3 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 3- to 4-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 1 to 2 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 4 to 6 months this year and 6 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 health care practitioners. The very next day, we had members of our field team trained and promoting the new indication at an oncology conference. and 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 2 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 1 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 1 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 2 or 3 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 4 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 RE

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 4 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. 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 KMT22A, 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. 5 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 6 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 2 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 2 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 2 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, 1 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, 1 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 an MRD-negative CR and went on to receive a stem cell transplant. Turning to the promising clinical activity observed among 9 efficacy evaluable NPM1 and KMT2A patients in the NCI trial at the dose level 1 or 2 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 7 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 2 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 '25 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 10 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 2 cycles of revumenib prior to transplant and revumenib was initiated at a median of 111 days or roughly 3 to 4 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 1 year. Patients had completed a median of 11 cycles post transplant at the time of the data cutoff. One patient continued for 2 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 10 patients were alive with no relapses, yielding an estimated 1-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 2 years post transplant. Turning now to axatilimab on Slide 13. I will briefly highlight 3 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 2 weeks and then transitioned to a double dose every 4 weeks. Among the 19 patients who switched, the 4-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 1 of 2 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 2Q, 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 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 2 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 3 FDA approvals and launches within roughly 1 year, a remarkable achievement. With 2 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. Operator?

[Operator Instructions] 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 1/3 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, longer utilization for patients.

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

You spoke about a 6- to 12-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?

Thanks, Corinne. Great question. Look, I think 2026, we said that in 2025, as we started with new patients staying on therapy in the range of 4 to 6 months, and that was really reflective of new patient starts and some patients coming back from -- on maintenance therapy post transplant. But the impact of that in terms of duration of therapy won't be felt really until 2026, where more patients will be returning from transplant and receiving maintenance. We expect, obviously, to have a launch now with NPM1. So additional patients will be receiving therapy. And then we'll have some of those patients go to transplant as well. But I think the mix of patients between KMT2A where you'll have slightly longer duration of treatment based on the fact that more patients in KMT2A will go to transplant than NPM1. That mix of patients will be -- will have a slightly longer duration of therapy. NPM1, larger patient population. So, we expect more patients to be on drug than perhaps what we'll see with KMT2A ultimately, but a slightly shorter duration based on the fact that fewer patients will go to transplant, although some will. So, it's the mix of those 2 patient populations that we believe will drive to 6 to 12 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 revumenib 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 1/3 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 physician, 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, so 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 2 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 2 to 3 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 2 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 1/3 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.

So, as you know, payer access formulary coverage for Revuforj really since launch has been simply outstanding. By month 5, we hit 97% formulary coverage. So, in essence, unfettered access for commercial Part D and Medicaid patients. There has, of course, been some off-label prescriptions outside of KMT2A. We know that it's been about 10% since launch, and that will obviously -- the usage will grow with the indication. But we haven't had any pushback from payers for the most part, even in advance of the NPM1 indication. Once the publication came out in May in blood, obviously, the NCCN listing was in the third week of September. That's really what payers need to get products covered. Even when they're not yet indicated, obviously, the indication is going to accelerate that. So, the payer team has been talking to payers since we submitted the sNDA earlier this year, coverage will build quickly. But in the interim, Peter, as coverage builds, the claims will be adjudicated and paid for. So, patients will still enjoy open access to Revuforj moving forward until that coverage is 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 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, Ellen, thanks for the question. I'll start off with some comments about the quarter, and then I'll turn it over to Steve to talk about the launch trajectory. So first, strong start to the quarter. I'd say HCPs are excited. As you'd imagine, awareness is quite high. Increase in prescriptions, we're seeing it, accounts are ordering and have expanded. The setup for the forward, I think, is quite positive. We had guidelines as you know, late September. So that didn't impact the quarter too much, but sets us up well for this quarter coming and approval in October. So, the combination really sets our launch at a very -- we think, in a very good way. So, we expect a solid Q4, and we expect this to add meaningfully to the book of business that we have in KMT2A. And we talked about the factors that will drive KMT2A business, which is new patient starts steady as well as maintenance and patients coming back from -- on to maintenance therapy, which will grow. So, we're expecting a good Q4. Maybe I'll turn it over to Steve to talk about 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 3 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, 2 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 6 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 it is meaningful. It's really 2 to 3 patients to gain some serious muscle memory in use. And the last piece, which we highlighted on this call is really the ongoing clinical development program of the data that we've been supporting and whether they're collaborative studies, ISTs and health economic work. That data set will build over time, giving physicians the kind of data sets and data points they need to continue to use this drug widely. So, we feel we're in a great position moving forward.

Yes. And I would just add that, I think we have -- it's quite simple in terms of our view on competition, Revuforj has the broadest and strongest efficacy profile. This is a very much of an efficacy-driven market where you have physicians looking to get patients to remission. It's -- they're very sick and they need, I think, a very strong drug to drive home and get patients into remission. And Revuforj is that and it has the broadest profile to achieve that in all types of patients. So, I think we're in a very good position going into this launch. And we have a pretty simple view on how the competitive dynamic will play out. We should dominate this market.

Your next question will come from Stephen Willey with Stifel.

Just one, I guess, on the soon to initiate REVEAL trial in frontline patients with intensive chemo. I know we don't have protocol details yet, but I was just curious about how you're philosophically thinking about specifically evaluating the contribution of maintenance therapy within the protocol itself, just given what J&J now appears to be doing in the frontline setting and whether you think trial design differences may have some kind of competitive implications on the labeling front as it pertains to maintenance therapy explicitly?

Steve, thanks. A great and important question about how do we think about evaluating or how are we evaluating maintenance therapy in our REVEAL trial. So maybe I'll turn it over to Nick to take that.

Yes, it's an important question. It's something we've thought a lot about, and we're looking forward to, as we've indicated, starting our REVEAL program soon this quarter and very encouraged actually by the data that we've already presented and we'll follow up more in terms of combinations with intensive chemotherapy, which looks very encouraging. So, maintenance is an important question. And the way we're thinking about this is that we have a number of studies that will generate data that support maintenance, looking at different doses, different approaches that will support treatment practice. So, maintenance is obviously a consideration within the pivotal studies themselves. All of our studies allow for maintenance after transplant, and we'll be able to ascertain some data from that. But in terms of the overall profile, we'll be looking at a broad body of evidence to support use in the maintenance setting in the front line.

Your next question will come from Yigal Nochomovitz with Citigroup.

I was just curious, when you look at the trends between the community practices and academic, are you seeing any differences there in terms of the percent going to transplant? And then related to that, are you seeing any differences in those segments in the percent returning to maintenance post transplant?

Yigal, thanks for the questions. I'm going to turn it over to Steve to kind of to address that. First question relates to, are we seeing differences in transplant between community practices and academic practices?

Yes. So, we know there's usage across academia as well as community. Majority is in academics, and these patients are very sick. That's not uncommon, whether it's for KMT2A, we expect that early for NPM1. So, the majority has been in academia. We're not able to peel apart the rates -- the treatment rates and maintenance. We do have some claims analysis, which trails. Some of that data that we've been shared today is from that claims analysis. Perhaps as the data set grows, we'll be able to pull apart that dynamic. But for now, it's -- the rates we've shared are really across the spectrum.

Okay. And I know you mentioned, obviously, for NPM1, you'll have less transplants. But nonetheless, since the drug was just approved in the expanded label, -- is there a situation where some patients that did have transplants that were NPM1 could still get Revuforj as maintenance even if they didn't get it before or that wouldn't happen?

Excellent question, Yigal. I'll turn it over to Nick.

Actually, yes. Interestingly, we are seeing that. And in fact, there was a reported case in the real-world series that I mentioned from Moffitt, you'll see one patient actually start on Revuforj having I assume as a function of timing, not had treatment prior to the transplant. So, there is now -- and we've heard from some other centers as well that there is a desire if they haven't had Revuforj prior to the transplant that they would start on it as a maintenance therapy afterwards.

Your next question will come from Justin

Congrats on the quarter. Just wondering if you could give us an update on how the safety profile has been faring in the real world? Do you see patients discontinuing the drug at all for any adverse events?

Justin, thanks. I'm going to turn it to Nick for a safety profile.

Yes. I would say -- I mean, we -- I would say we probably spoke to 1,000 physicians since the launch and the reception has been very favorable. Again, we've talked about very consistent safety profile. They're very familiar with managing it, in particular, very low rates of serious cardiac complications across our clinical trial program of over 1,000 patients. So, it's very well managed. We actually see, as you can see from the data -- the extensive data we're going to be presented at ASH, you see very low rates of discontinuations from therapy. The adverse event profile is well managed, and that's consistent with what we see in the commercial use as well. They're very experienced in using the drug, and it's well managed.

Your next question will come from Salim Syed with Mizuho.

Great. Congrats on the quarter, guys. Just one for me as well on the safety side. I know people are focused and you guys mentioned this on the approval call, the one case of Torsades, it's now listed in the black box there. I know one case, and you mentioned previously, you don't expect things to really change with it. And I get that. But as you kind of think about first line here where there are more patients and you are treating thousands of patients per year, is it not reasonable to think here that you're going to get more cases like that, and that's something that you're going to have to educate or manage around, especially if zifto does not end up with that on the label?

Nick, do you want to?

Well, I think actually, the answer is no because the rates in the frontline setting actually seem to be lower. This may have something to do with patients may be fitter newly diagnosed. They've had low -- they haven't had exposure to prior anthracyclines and things. So we're seeing low rates. The other benefit of our frontline studies, of course, is that they will be randomized. There'll be a control arm. It will be much easier to ascertain the true rates of drug-related side effects with the control. So, I think it will be much more informed. And based on what we've seen to date, we're really seeing very low rates of serious cardiac events or discontinuations.

Yes. I'd just add on top of that, I mean, we -- as Nick mentioned, we've talked to hundreds of physicians since launch. And here's the takeaway. I mean, they're excited about the profile. Revuforj's efficacy sort of stands out for sure, very manageable safety profile. They're not changing the way they practice based on the label and what they've seen. There's no new monitoring. So, they've been doing the same thing they've been doing for a year as we've launched KMT2A, and they've also treated NPM1 patients successfully during this time. So, I think they see Rev as a game changer for their patients and efficacy really matters the most here, and that's what they're focused on. So that's really where we lead things.

Your next question will come from David Dai with UBS.

Just a question on the 35% to 40% patients who resumed Revuforj post transplantation in third quarter. Could you maybe provide some additional detail around the timing of the maintenance use? How long is the drug holiday before we'll see them coming back to the maintenance therapy?

Great, David. Thanks for the question. Very simple. So, what we're seeing in our clinical experience, our commercial experience is reminiscent of what we've seen in our clinical experience, which is patients get about 2 to 3 months of therapy. For the ones who go to transplant, they usually get their response in that time frame. They go to transplant, so they're off Revuforj for a period of time, and then they resume about 3 to 4 months later. So it's, call it, 6 -- in the range of 6 months from start to resumption of therapy in the maintenance setting.

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

Congrats on strong momentum. Actually, a lot of demand indicators aligned with our recent physician survey. So, on the KMT2A versus NPM1 revenue split being obviously 90 to 10 right now, are you able to comment on when you'd expect that to be a little bit more balanced or even NPM be a bit more dominant from a timing standpoint? I obviously recognize there are different dynamics here in play in terms of what you just commented on treatment duration and obviously, transplant dynamics and obviously, the larger starting patient population. And then I have a quick follow-up.

Yes. Thanks for the question. I think you answered it yourself. It's 2 different populations of patients. KMT2A is smaller than NPM1. We're expanding the population 2 to 3x the size with NPM1. More patients do go to transplant that are KMT2A will have a slightly longer duration of treatment based on the fact that there's a group of patients -- a growing group of patients in KMT2A going to transplant and then coming back on for maintenance. NPM1 will have its own dynamics. But we do have the best profile, we believe, in both those segments. We're widely indicated for AML, ALL for KMT2A, adults and pediatrics, and we extend adults and pediatrics with NPM1. So, we do have the broadest profile. We do expect to capture the largest share in NPM1 and dominate for both segments. So, I think this is -- it's a little difficult to tease out what's the contribution of parts at this point, but we do think that we'll have a majority share in both segments.

Okay. And on the impressive frontline AML data set from the save all-oral regimen, I believe that was and then the intensive chemo combination. We also saw a couple of peer frontline data sets that were released this morning. Any updated thoughts on how you're thinking of competitive positioning and even maybe regulatory strategy with different combination regimen trials in frontline based on some of this data? And the post-transplant 1-year relapse-free rate was 100%, if I heard 1-year EFS. Is that not something you could include in the label at some point? Or would you have to do that post maintenance frontline trial to get there?

Yes. Great questions, I'm going to turn it over to Nick to maybe address each of those if you can.

Yes, I would be happy to. And I think we're going to have a very dominant presence at ASH, given the data we're going to be presenting across 12 abstracts. And as you say, very compelling data in the frontline setting from both our SAVE oral data, but also now our emerging data from intensive chemotherapy, which we will be updating. You'll see more numbers and more follow-up from both of the studies that we'll be presenting. When we look across, I would say, the competitive landscape, there's going to be a lot of combination data presented at ASH. I think that overall, the profile for revumenib really is quite compelling, both in terms of the efficacy that we're showing consistently now, particularly when you look at the subsets of patients like KMT2A, where we're seeing a 100% response rate and 100% MRD negativity in what we've reported. It's really quite unparalleled. And again, it speaks to the depth and the breadth of the profile that we see with revumenib. So, I think we're very well positioned in the data we're going to be presenting. And when you think that, that's adding on to data that we've already presented like the BEAT-AML study previously in frontline in combination with ven/aza, it bodes very well for all of our frontline programs, both the REVEAL programs with intensive chemotherapy and also the EVOLVE-2 study that we're doing in collaboration with HOVON, which is well underway and has been enrolling since earlier this year. So yes, I think a strong profile and nothing that looks differentiating in any of the other combination data we've looked at to date at ASH.

Our final question today is from the line of Jason

Congrats on the progress. I was hoping you could speak to the impact of the NPM1 approval on your gross to net and inventory trends as we head into the fourth quarter and early next year. Given the size of the population relative to the KMT2A, I have to imagine that some of the headwinds may pivot to tailwinds and at a much more substantive impact. And then I guess, secondarily, if a patient returns to Revuforj following a transplant, how challenging is that, at least from an administrative or payer perspective? How difficult is it sort of restarting a patient like that?

Jason, thanks for the questions. First question, impact of on GTN for NPM1. Keith, I'll address that.

Yes. The first one is a 2-part question. With respect to inventory, Jason, we don't expect any changes. The 2- to 3-week guidance that we've given is going to grow in absolute terms as volumes grow. So, it's based on a trailing period of demand. So, we expect inventory levels in our specialty distribution channel to stay at 2 to 3 weeks. With respect to your question on gross to net, the NPM1 indication may shift the mix in terms of payers. As you know, we offer no commercial rebates. There's the statutory rebates that I mentioned earlier in response to another question. But we have pretty good visibility, and we expect to remain in that 20% to 25% gross to net range.

Steve, do you want to take the second question?

Yes. And maybe just a comment on the gross to net. I mean, NPM1 patients tend to be older, so Keith write the mix, it could go to more Medicare Part D from commercial. So, there might be some slight impact. In terms of, Jason, the question on impacting payers and this is patients coming back post a successful transplant as a restart or as we call maintenance treatment, we don't expect any pushback from payers. There's been so few pushback from payers at this point really throughout the launch. And a lot of this is payers understand the unmet need, the value the drug brings. They've accepted the price. So, a vast majority of prescriptions are being paid for regardless of if they're KMT2A, NPM1 maintenance or even for other off-label use. So, we don't expect any pushback from payers on patients returning to a maintenance therapy.

This concludes our question-and-answer session. I will now turn the floor over to Mr. Michael Metzger for any closing remarks.