Syndax Pharmaceuticals Q3 2025 Earnings Call Transcript

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Provided by Quartr
November 3, 2025

Key Takeaways

  • Positive Sentiment: Strong commercial momentum: Q3 total revenue was $45.9M with Revyforge net sales of $32M, prescription and new patient starts up ~25% quarter-over-quarter, and Nictimvo annualizing near $200M with Syndax's Q3 collaboration contribution of $13.9M.
  • Positive Sentiment: FDA approval for Revyforge in relapsed/refractory NPM1 (Oct 24) plus prior NCCN listing tripled the addressable relapsed/refractory AML population to ~6,500 patients and makes Revyforge the first menin inhibitor approved across multiple leukemia subtypes and ages.
  • Positive Sentiment: Management says Syndax is on a clear path to profitability with a strong balance sheet (~$456M in cash and investments), growing cash contributions from Revyforge and Nictimvo, and an operating expense base expected to remain stable.
  • Negative Sentiment: Net revenue growth lagged prescription growth (12% vs ~25%) due to higher gross‑to‑net adjustments (20%–25% guidance range), increased 340B and Medicare/Medicaid exposure, and a slight channel inventory drawdown—factors that could temper near‑term top‑line trends.
  • Negative Sentiment: Regulatory/safety caution: a single serious cardiac event (Torsades) prompted label warning; management describes low real‑world rates, but expansion into frontline settings could increase scrutiny and monitoring requirements.
AI Generated. May Contain Errors.
Earnings Conference Call
Syndax Pharmaceuticals Q3 2025
00:00 / 00:00

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Operator

Good day, everyone, and welcome to the Syndax third quarter 2025 earnings conference call. Today's call is being recorded. If you would like to ask a question following the company's prepared remarks, please press star five during the call. At this time, I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

Sharon Klahre
Head of Investor Relations at Syndax

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 Kloster, 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 two.

Sharon Klahre
Head of Investor Relations at Syndax

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.

Michael Metzger
Michael Metzger
CEO at Syndax

Thank you, Sharon. Good afternoon, and thank you all for joining us. Starting with slide three, 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, two 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.

Michael Metzger
Michael Metzger
CEO at Syndax

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 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.

Michael Metzger
Michael Metzger
CEO at Syndax

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 pause 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 adults and children one year of age or older.

Michael Metzger
Michael Metzger
CEO at Syndax

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 datasets 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 one week since approval, we have already engaged with hundreds of physicians, and feedback has been very positive.

Michael Metzger
Michael Metzger
CEO at Syndax

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 one-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, five-month median duration of CR/CRh, 17% transplant rate, and a two-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.

Michael Metzger
Michael Metzger
CEO at Syndax

Moving to Niktimvo, in the second quarter of launch, our partner Incyte Corporation reported $45.8 million in Niktimvo net revenue, a robust 27% increase over the prior quarter. Within just the first eight months of launch, Niktimvo is annualizing at nearly $200 million and tracking in line with first-year sales of Sanofi's Rezurock, which reached over $500 million in annual U.S. net sales within the first three years of launch in the same indication. Importantly, Niktimvo is profitable to Syndax with our 50% share of the Niktimvo product contribution amounting to $13.9 million for the third quarter. As sales continue to ramp, we expect the proportion of net revenue retained by Syndax to materially grow over time.

Michael Metzger
Michael Metzger
CEO at Syndax

We remain on the road to profitability with growing contributions from Revuforj and Niktimvo, a solid balance sheet, and an operating expense base that will remain stable over the next few years while fully funding our strategic priorities. Most notably, our strategic priorities include the expansion of Revuforj and Niktimvo into the frontline setting, which would unlock a combined market opportunity exceeding $10 billion. Enrollment is well underway in EVOLVE-2, the first pivotal frontline trial for a menin inhibitor to start enrolling patients. We have the right strategy and partnerships to flawlessly execute this trial and be the first to frontline with a menin inhibitor. With Niktimvo, two frontline trials are ongoing in combination with standard-of-care therapies that could transform the treatment of chronic GVHD. With that, I will turn the call over to Steve to discuss our commercial progress in more detail. Steve.

Steve Closter
Chief Commercial Officer at Syndax

Thank you, Michael. Starting with Revuforj on slide four, 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 second 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 second quarter.

Steve Closter
Chief Commercial Officer at Syndax

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 incidence within the first year of launch, and that is a fantastic result.

Steve Closter
Chief Commercial Officer at Syndax

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.

Steve Closter
Chief Commercial Officer at Syndax

We estimate that 35%-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 twelve months in 2026 as treatment patterns further mature. Let's turn to NPM1, the next important growth driver for Revuforj.

Steve Closter
Chief Commercial Officer at Syndax

As shown on slide five, 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+ market opportunity. Moving to slide six. 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, 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.

Steve Closter
Chief Commercial Officer at Syndax

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%-45% of patients with AML is a huge benefit to practitioners and payers.

Steve Closter
Chief Commercial Officer at Syndax

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 one and tier two 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.

Steve Closter
Chief Commercial Officer at Syndax

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.

Steve Closter
Chief Commercial Officer at Syndax

Turning to Niktimvo on slide seven, 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 continues to grow, with 90% of bone marrow transplant centers in the U.S.

Steve Closter
Chief Commercial Officer at Syndax

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 eight. 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.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

It's a pleasure to be on the call today. Thank you, Steve. To discuss the strong presence Syndax will have at ASH with 23 abstracts accepted for presentation, including six oral presentations highlighting our scientific leadership in menin inhibition and CSF1R 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 nine 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 dataset. Fifteen patients received Revuforj in the relapsed/refractory setting, two in the frontline, and one after stem cell transplant without prior Revuforj treatment.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

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 one 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.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

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 three. The first real-world dataset 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.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

The high rate of combination therapy observed highlights physicians' comfort with revumenib 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 datasets we will be collecting and presenting in partnership with leading physicians and centers. Turning to slide ten 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.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

Among newly diagnosed patients with NPM1 or KMT2A, 88% of evaluated 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 two and no events of DS above grade three. This is an important dataset that builds on the encouraging results observed in the Beat AML trial of revumenib with venetoclax and azacitidine in newly diagnosed patients with AML.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

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 Venclexta 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 one data supporting Revuforj 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.

Nick Botwood
Head of Research and Development and Chief Medical Officer at 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 one was revumenib at 110 or 220 mg every 12 hours with or without strong CYP3A4 inhibitor, respectively. Dose level two 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 two. This was one grade five event of typhlitis, or severe inflammation of the intestine, a complication that is known to occur in patients receiving intensive chemotherapy.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

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 three QTc prolongation was reported at dose level one. 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 nine efficacy evaluable NPM1 and KMT2A patients in the NCI trial at 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 Revuforj. The median time to full count recovery, including both neutrophils and platelets, was 25.5 days among patients with CR.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

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 Revuforj program, which will evaluate revumenib in combination with intensive chemotherapy in newly diagnosed fit patients with NPM1 or KMT2A. We remain on track to initiate Revuforj 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.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

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 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 datasets. 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.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

At the last follow-up, all 10 patients were alive with no relapses, yielding an estimated one year event-free survival of 100%. This is a very encouraging result 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 one 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 actually actively recruiting at City of Hope and Dana-Farber Cancer Institute, is planning to continue revumenib for two years post-transplant.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

Turning now to axatilimab on slide 13, I will briefly highlight three axatilimab abstracts that underscore the potential for long-term benefit in relapsed/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 nine patients who switched, the four-week dosing was well tolerated with a median of 1.7 years on therapy after the dosing change.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

The third abstract reports interim safety data from 44 patients enrolled in the ongoing phase two trial of axatilimab with ruxolitinib in newly diagnosed chronic GVHD. The data show 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. With that, I will hand over the call to Keith to discuss our financials.

Keith Goldan
CFO at Syndax

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 2025, we reported Revuforj net revenue of $32 million. Quarter-over-quarter sales growth was driven by demand as inventory levels remained at two to three 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 second quarter, while still within the 20%-25% guidance range we previously provided. The increase was due to a 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 in inventory in the channel this quarter, while still within the two to three-week range that we previously guided.

Keith Goldan
CFO at Syndax

Looking ahead, we expect sales growth to meaningfully accelerate over the coming quarters with the approval in NPM1. 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%-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.

Keith Goldan
CFO at Syndax

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 30th. 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're 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.

Michael Metzger
Michael Metzger
CEO at Syndax

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 frontline and beyond. We have an outstanding team that is consistently executing at the highest level, culminating in three FDA approvals and launches within roughly one year, a remarkable achievement. With two exceptional product launches underway, a strong balance sheet, and a 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

At this time, I would like to remind everyone, in order to ask a question, please press star, then the number five on your telephone keypad.If you would like to withdraw your question, press star and the number five once again. We'll pause for just a moment to compile the Q&A roster. The first question is from Anupam Rama with JPMorgan. Your line is now open.

Priyanka Anand
Priyanka Anand
Executive Director of Consumer and Community Banking at JPMorgan

Hi guys, 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? Thanks.

Michael Metzger
Michael Metzger
CEO at Syndax

Yeah, thanks, Priyanka, for the question. I'll take that. 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.

Michael Metzger
Michael Metzger
CEO at Syndax

That's a stark change from what we've seen in our clinical trial where third and fourth line was the average patient. 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 a third go to transplant. We've actually seen quite a shift and that we think will manifest in patients staying on drug longer over time in KMT2A. That's been very meaningful. We expect with NPM1, these patients are getting to transplant as well. We're also seeing high rates of response. About half the patients get to response.

Michael Metzger
Michael Metzger
CEO at Syndax

We do expect them to be treated earlier and earlier in the treatment journey. As we've talked about, patients are also being treated in combination. That will drive patients to earlier utilization within their journey. 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.

Operator

Your next question will come from Corinne Johnson with Goldman Sachs. Your line is now open.

Corinne Johnson
Corinne Johnson
VP of Equity Research at Goldman Sachs

Good afternoon. You spoke about a six- 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? When could that start to be reflected in the revenue trajectory? Thanks.

Michael Metzger
Michael Metzger
CEO at Syndax

Thanks, Corinne. Great question. I think 2026, we said that in 2025, as we started with new patients, staying on therapy in the range of four to six months, and that was really reflective of new patient starts and some patients coming back from on maintenance therapy post-transplant. 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. Then we'll have some of those patients go to transplant as well. 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 have a slightly longer duration of therapy.

Michael Metzger
Michael Metzger
CEO at Syndax

NPM1, larger patient population, so we expect more patients to be on drug than perhaps what we will see with KMT2A ultimately, but a slightly shorter duration based on the fact that fewer patients will go to transplant, although some will. It is the mix of those two patient populations that we believe will drive to 6-12 months in the second year.

Operator

Your next question will come from Brad Canino with Guggenheim.

Brad Canino
Brad Canino
Biotechnology Equity Research Analyst at Guggenheim

Hey, great. Thanks for having the question. Nice commercial momentum on the quarter. This 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%-40% you are reporting is weighed down by the bolus of recent patients getting transplants, but not yet undergoing the ability to get maintenance. Were you able to do a longitudinal analysis at all to understand where that restart rate number can grow to? Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax

Excellent question, Brad. I think we have seen some progress this quarter in the restart rate where we saw last quarter about a third of patients restarting maintenance therapy. Now it is up to about 35%-40%. We do believe that will grow over time. Additional patients, steady flow. We have 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 do not have an upper limit of what percentage of patients will come back, although what we have heard from physicians is that they are very keen to put them back on therapy.

Michael Metzger
Michael Metzger
CEO at Syndax

What we have heard is as many as 80%, 90%. They have given figures that they would say almost all their patients. It is hard to estimate what the upper limit is and of what percentage of patients will come back. It is impacted by other factors that are beyond the control of a physician if a patient has extenuating circumstances. I think the inclination is to bring them back and put them on therapy. We will just have to wait and see how that manifests. It is a good sign that even now we are starting to see more patients come back on.

Operator

Your next question will come from Clara Dong with Jefferies.

Clara Dong
Clara Dong
VP of Biotechnology Equity Research at Jefferies

Good afternoon. Thanks for taking our question. 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 a patient mix shifts from predominantly KMT2A in the third quarter to include more NPM1 patients going forward? Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax

Yeah, Keith, do you want to take that question?

Keith Goldan
CFO at Syndax

Yeah, Clara, thanks for the question. We really do not 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.

Operator

Your next question will come from Peter Lawson with Barclays.

Peter Lawson
Peter Lawson
Managing Director and Senior Biotechnology Equity Analyst at Barclays

Great. Thank you. Thanks for taking my questions. Just on the delta between quarter-over-quarter growth of registrars versus the Rx rate. Kind of in any way to break down that gap between versus inventory timing that we should be thinking about, or any changes that we should be thinking about going forward? I have a question just on if there's been any friction with getting NPM1 authorizations and payer access.

Michael Metzger
Michael Metzger
CEO at Syndax

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

Keith Goldan
CFO at Syndax

Yeah, 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 are generally two factors that play into that. It's generally differences in gross to net and differences in inventory stocking. As I said, both can fluctuate quarter to quarter.

Keith Goldan
CFO at Syndax

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%-25%. We did have slightly higher 340B chargebacks and slightly higher Medicaid and 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. 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%.

Michael Metzger
Michael Metzger
CEO at Syndax

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

Steve Closter
Chief Commercial Officer at Syndax

I think the other part of Peter's question was just friction on the payer side. Yes. As you know, payer access, formulary coverage for Revuforj really since launch has been simply outstanding. By month five, we hit 97% formulary coverage. 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. We haven't had any pushback from payers for the most part, even in advance of the NPM1 indication.

Steve Closter
Chief Commercial Officer at Syndax

Once the publication came out in May in Blood, obviously, the NCCN listing was in the third week of September. That is really what payers need to get products covered even when they are not yet indicated. Obviously, the indication is going to accelerate that. The payer team has been talking to payers since we submitted the SNDA earlier this year. Coverage will build quickly. In the interim, Peter, as coverage builds, the claims will be adjudicated and paid for. Patients will still enjoy open access to Revuforj moving forward until that coverage is permanent.

Operator

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

Ellen Horste
Ellen Horste
Equity Research Associate at TD Cowen

Hi guys. 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 third quarter where you did have that inclusion in the NCCN guidelines. 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 is a larger population, but it is likely to face some competition. Any thoughts there would be helpful. Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax

Yeah, Ellen, thanks for the question. I will start off with some comments about the quarter, and then I will turn it over to Steve to talk about the launch trajectory. First, strong start to the quarter. I would say HCPs are excited. As you can imagine, awareness is quite high. Increase in prescriptions, we are seeing it. Accounts are ordering and have expanded. Setup for the forward, I think, is quite positive. We had guidelines, as you know, late September.

Michael Metzger
Michael Metzger
CEO at Syndax

That did not impact the quarter too much, but sets us up well for this quarter coming and approval in October. The combination really sets our launch at a very, we think, in a very good way. We expect a solid fourth quarter, and we expect this to add meaningfully to the book of business that we have in KMT2A. We talked about the factors that will drive KMT2A business, which is new patient starts, steady, as well as maintenance, and patients coming back onto maintenance therapy, which will grow. We are expecting a good fourth quarter. Maybe I will turn it over to Steve to talk about launch trajectory NPM1.

Steve Closter
Chief Commercial Officer at Syndax

Yeah, just to add on to Michael's comments, I mean, awareness and excitement around the new indication is incredibly high.

Steve Closter
Chief Commercial Officer at Syndax

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 are excited about the launch. I know physicians are as well. There are three main drivers as we think about this. We will 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. We believe we have the best data. That's what physicians tell us. The drug is well tolerated, range of doses.

Steve Closter
Chief Commercial Officer at Syndax

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. 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. That experience accounts have is meaningful. It's really two to three patients to gain some serious muscle memory and use.

Steve Closter
Chief Commercial Officer at Syndax

The last piece, which we highlighted on this call, is really the ongoing clinical development program, 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. We feel we're in a great position moving forward.

Michael Metzger
Michael Metzger
CEO at Syndax

Yeah, thanks. 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 much of an efficacy-driven market where you have physicians looking to get patients to remission. They're very sick, and they need, I think, a very strong drug to drive home and get patients into remission. Revuforj is that. It has the broadest profile to achieve that in all types of patients.

Michael Metzger
Michael Metzger
CEO at Syndax

I think we're in a very good position going into this launch. We have a pretty simple view on how the competitive dynamic will play out. We should dominate this market.

Operator

Your next question will come from Stephen Willey with Stifel.

Stephen Willey
Stephen Willey
Managing Director at Stifel

Yeah, good afternoon. Thanks for taking the question. 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. Thanks.

Michael Metzger
Michael Metzger
CEO at Syndax

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. Maybe I'll turn it over to Nick to take that.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

Yes, it's an important question. It's something we've thought a lot about. We're looking forward to, as we've indicated, starting our REVEAL program soon this quarter. Very encouraged, actually, by the data that we've already presented and will follow up more in terms of combinations with intensive chemotherapy, which looks very encouraging. Maintenance is an important question. 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. 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. In terms of the overall profile, we'll be looking at a broad body of evidence to support our use in the maintenance setting in the frontline.

Operator

Your next question will come from Yigal Nochomovitz with Citigroup.

Yigal Nochomovitz
Yigal Nochomovitz
Director at Citigroup

Hi, thanks for taking the question. 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? Related to that, are you seeing any differences in those segments in the percent returning to maintenance post-transplant?

Michael Metzger
Michael Metzger
CEO at Syndax

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

Steve Closter
Chief Commercial Officer at Syndax

Yeah. 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. The majority has been in academia. We're not able to peel apart the treatment rates and maintenance. We do have some claims analysis, which trails. Some of that data that we've shared today is from that claims analysis. Perhaps as the data set grows, we'll be able to pull apart that dynamic. For now, the rates we've shared are really across the spectrum.

Yigal Nochomovitz
Yigal Nochomovitz
Director at Citigroup

Okay, thanks. I know you mentioned, obviously, for NPM1, you'll have less transplants. 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?

Michael Metzger
Michael Metzger
CEO at Syndax

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

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

Actually, yes. Interestingly, we are seeing that. In fact, there was a reported case in the real-world series that I mentioned from Moffitt. You'll see one patient actually started on Revuforj having, I assume, as a function of timing, not had treatment prior to their transplant. 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.

Yigal Nochomovitz
Yigal Nochomovitz
Director at Citigroup

Wow, very interesting. Okay, thank you.

Michael Metzger
Michael Metzger
CEO at Syndax

Yeah, thanks for the question, Yigal.

Operator

Your next question will come from Justin Zelin with BTIG.

Justin Zelin
Justin Zelin
Director and Biotechnology Equity Research Analyst at BTIG

Thanks for taking the question. Congrats on the quarter. Just wondering if you'd 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? Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax

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

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

Yeah, I would say, I mean, I would say we've probably spoke to 1,000 physicians since the launch, and the reception has been very favorable. Again, we've talked about a 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. It's very well managed.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

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.

Operator

Your next question will come from Salim Syed with Mizuho.

Salim Syed
Salim Syed
Managing Director and Senior Biotechnology Equity Research Analyst at Mizuho

Great. Congrats on the quarter, guys. Just one from me as well on the safety side. I know people are focused, and you guys mentioned this on the approval call, the one case at Torsades. It's now listed in the black box there. I know it's just one case. You mentioned previously, you don't expect things to really change with it. I get that. If 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? That's something that you're going to have to educate or manage around, especially if Zypto does not end up with that on the label. Thank you.

Michael Metzger
Michael Metzger
CEO at Syndax

Nick, do you want to?

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

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 maybe fit and newly diagnosed. They haven't had exposure to prior anthracyclines and things. 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'll be much easier to ascertain the true rates of drug-related side effects with the control. I think it'll be much more informed. And based on what we've seen today, we're really seeing very low rates of serious cardiac events or discontinuations.

Michael Metzger
Michael Metzger
CEO at Syndax

Yeah, I just add on top of that. On top of that, I mean, 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. They've been doing the same thing they've been doing for a year as we've launched KMT2A. They've also treated NPM1 patients successfully during this time. 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. That's really where we leave things.

Salim Syed
Salim Syed
Managing Director and Senior Biotechnology Equity Research Analyst at Mizuho

Okay. Thanks, Mike. Thanks, Nick.

Michael Metzger
Michael Metzger
CEO at Syndax

Thanks, Salim.

Operator

Your next question will come from David Dai with UBS.

David Dai
David Dai
Director at UBS

Thanks for taking my questions. Just a question on the 35%-40% patients who resumed Revuforj post-transplantation 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?

Michael Metzger
Michael Metzger
CEO at Syndax

Great, David. Thanks for the question. Very simple. 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 two to three 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 of Revuforj for a period of time, and then they resume about three to four months later. Call it in the range of six months from start to resumption of therapy in the maintenance setting.

Operator

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

Mayank Mamtani
Mayank Mamtani
Senior Managing Director and Group Head of Healthcare Equity Research at B. Riley

Yes, good afternoon, Dean. Thanks for taking our questions and congrats on strong momentum. Actually, a lot of demand indicators aligned with our recent physician survey. On the KMT2A versus NPM1 revenue split being obviously 90-10 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. Then I have a quick follow-up.

Michael Metzger
Michael Metzger
CEO at Syndax

Yeah, thanks for the question. I think you answered it yourself. It's two different populations of patients. KMT2A is smaller than NPM1. We're expanding the population two to three times the size with NPM1. More patients do go to transplant that are KMT2A. We'll have a slightly longer duration of treatment based on the fact that there's 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.

Michael Metzger
Michael Metzger
CEO at Syndax

So we do have the broadest profile. We do expect to capture the largest share in NPM1 and dominate for both segments. I think 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.

Mayank Mamtani
Mayank Mamtani
Senior Managing Director and Group Head of Healthcare Equity Research at B. Riley

Okay. And on the impressive frontline AML data set from the SAVE 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 one-year relapse rate was 100%, if I heard one-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? Thanks for taking our questions.

Michael Metzger
Michael Metzger
CEO at Syndax

Yeah, great questions. I'm going to turn it over to Nick to maybe address each of those if he can.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

Yeah, I'd be happy to. 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. As you say, very compelling data in the frontline setting from both our SAVE 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.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

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. It speaks to the depth and the breadth of the profile that we see with revumenib. I think we're very well positioned in the data we're going to be presenting. 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 venetoclax, 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.

Nick Botwood
Head of Research and Development and Chief Medical Officer at Syndax

Yeah, I think a strong profile and nothing that looks differentiating in any of the other combination data we've looked at today at ASH.

Mayank Mamtani
Mayank Mamtani
Senior Managing Director and Group Head of Healthcare Equity Research at B. Riley

Thank you. Look forward to seeing you in Orlando.

Michael Metzger
Michael Metzger
CEO at Syndax

Wonderful. Thank you so much. Us as well.

Operator

Our final question today is from the line of Jason Zemansky with Bank of America.

Jason Zemansky
Jason Zemansky
VP of Biotechnology and Pharmaceuticals Equity Research at Bank of America

Good evening. Congrats on the progress, and thanks for squeezing us in. 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. 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? Thanks.

Michael Metzger
Michael Metzger
CEO at Syndax

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

Keith Goldan
CFO at Syndax

Yeah. Actually, the first one is a two-part question. With respect to inventory, Jason, we don't expect any changes. The two to three-week guidance that we've given is going to grow in absolute terms as volumes grow. It's based on a trailing period of demand. We expect inventory levels in our specialty distribution channel to stay at two to three 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 are the statutory rebates that I mentioned earlier in response to another question. We have pretty good visibility, and we expect to remain in that 20%-25% gross to net range.

Michael Metzger
Michael Metzger
CEO at Syndax

Steve, you want to take the second question?

Steve Closter
Chief Commercial Officer at Syndax

Yeah, and maybe just a comment on the gross to net. I mean, NPM1 patients tend to be older, so Keith, right, the mix. It could go to more Medicare Part D from commercial, so there may 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. A lot of this is payers understand the unmet need, the value the drug brings. They've accepted the price. A vast majority of prescriptions are being paid for, regardless of if they're KMT2A, NPM1, maintenance, or even for other off-label use. We do not expect any pushback from payers on patients returning to a maintenance therapy.

Jason Zemansky
Jason Zemansky
VP of Biotechnology and Pharmaceuticals Equity Research at Bank of America

Great. Thanks for the color.

Michael Metzger
Michael Metzger
CEO at Syndax

Thank you, Jason.

Operator

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

Michael Metzger
Michael Metzger
CEO at Syndax

Thank you all. We appreciate you all tuning in today to discuss our recent progress and the exciting milestones ahead. We look forward to seeing many of you at the upcoming UBS, Guggenheim, Stifel, Jefferies, and Evercore Conferences, as well as our ASH investor event in December. With that, have a great evening. Thank you.

Executives
Analysts
    • Ellen Horste
      Equity Research Associate at TD Cowen
    • Corinne Johnson
      VP of Equity Research at Goldman Sachs
    • Nick Botwood
      Head of Research and Development and Chief Medical Officer at Syndax
    • Stephen Willey
      Managing Director at Stifel
    • Peter Lawson
      Managing Director and Senior Biotechnology Equity Analyst at Barclays
    • Yigal Nochomovitz
      Director at Citigroup
    • Brad Canino
      Biotechnology Equity Research Analyst at Guggenheim
    • Sharon Klahre
      Head of Investor Relations at Syndax
    • Priyanka Anand
      Executive Director of Consumer and Community Banking at JPMorgan
    • Clara Dong
      VP of Biotechnology Equity Research at Jefferies
    • David Dai
      Director at UBS
    • Salim Syed
      Managing Director and Senior Biotechnology Equity Research Analyst at Mizuho
    • Keith Goldan
      CFO at Syndax
    • Mayank Mamtani
      Senior Managing Director and Group Head of Healthcare Equity Research at B. Riley
    • Jason Zemansky
      VP of Biotechnology and Pharmaceuticals Equity Research at Bank of America
    • Justin Zelin
      Director and Biotechnology Equity Research Analyst at BTIG
    • Steve Closter
      Chief Commercial Officer at Syndax
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