Q3 2025 Syndax Pharmaceuticals Inc Earnings Call

Speaker #1: At this time, I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

Speaker #2: 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.

Speaker #2: With me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer. Keith Kloster, Chief Commercial Officer.

Speaker #2: Dr. Nicholas 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 O'Dentlick, Chief Scientific Officer; and Dr. Angela Yanguli, Chief Strategy Officer.

Speaker #2: 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.

Speaker #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 form act of 1995.

Speaker #2: Actual results may differ materially from those indicated by these statements. As a result of various important factors, including those discussed in the risk factor section in the company's most recent quarterly report on Form 10Q.

Speaker #2: As well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, November 3rd, 2025 only. A replay of this call will be available on the company's website, www.sindax.com, following its completion.

Speaker #2: With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Speaker #3: 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.

Speaker #3: Importantly, the progress we made advances us on the road to profitability and furthers our leadership position in Menon Inhibition, an exciting new category that Syndax is uniquely positioned to lead across the relapse, refractory, and frontline setting.

Speaker #3: Starting with our commercial results for the quarter, we reported 45.9 million dollars in total revenue for the third quarter, representing strong 21% growth over the prior quarter.

Speaker #3: We are very encouraged by the launch metrics for both RevyForge and Nictimbo, 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.

Speaker #3: Net revenue for RevyForge was 32 million dollars in the third quarter, up 12% from the prior quarter, even with approximately a third of patients temporarily pausing treatment to receive a stem cell transplant.

Speaker #3: 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.

Speaker #3: RevyForge has become rapidly become the standard of care for relapse, refractory, KMT2A, and is widely being used early in the treatment paradigm with approximately 50% of usage in the second line.

Speaker #3: A growing number of KMT2A patients are proceeding to a potentially curative stem cell transplant after receiving RevyForge. This is a fantastic outcome for patients and clinicians.

Speaker #3: The use of RevyForge 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 Q4 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.

Speaker #3: In the third quarter and recent weeks, we have made major strides advancing another important RevyForge growth driver. On September 18th, RevyForge was added to the NCCN guidelines as a recommended treatment option for relapse, refractory, MPM1-mutated AML, ahead of the subsequent FDA approval. This speaks to the strength of our clinical data and physicians' enthusiasm for RevyForge.

Speaker #3: On October 24th, we received FDA approval for RevyForge, and relapse, refractory, MPM1 mutated AML tripling the size of our addressable patient population. This approval makes RevyForge the first and only Menon inhibitor that is FDA approved for multiple acute leukemia subtypes in adult and children, one year of age or older.

Speaker #3: The breadth of our indicated population highlights the compelling and consistent efficacy and tolerability of RevyForge across different patient populations. Nick will unpack the unique aspects of the RevyForge product profile when he reviews the key abstracts we will have this year at ASH.

Speaker #3: These datasets will add to the growing body of efficacy data that differentiate RevyForge from other Menon inhibitors. Our expansion into MPM1 is in full swing.

Speaker #3: And we are pleased with our early progress driving awareness of the new indication and generating demand among physicians who treat MPM1 patients. Importantly, these are the same physicians who treat KMT2A patients and have already built familiarity and trust with RevyForge and Syndax.

Speaker #3: In the one week since approval, we have already engaged with hundreds of physicians, and feedback has been very positive. They are enthusiastic to have RevyForge as the first highly efficacious targeted therapy indicated for relapse-refractory MPM1.

Speaker #3: 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 decision-making is driven by efficacy in acute leukemia, and we have differentiated efficacy data in multiple acute leukemia subtypes.

Speaker #3: In relapse, refractory, MPM1 specifically, we have shown unmatched data, including in approximately 50% overall response rate, five-month median duration of CRCRH, 17% transplant rate, and a two-year median overall survival observed among responders.

Speaker #3: While CRCRH 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.

Speaker #3: Moving to Nictimbo, in the second quarter of launch, our partner Insight reported $45.8 million in Nictimbo net revenue, a robust 27% increase over the prior quarter.

Speaker #3: Within just the first eight months of launch, Nictimbo is annualizing at nearly $200 million and tracking in line with first-year sales of Sanofi's Rezuroc, which reached over $500 million in annual U.S. net sales within the first three years of launch in the same indication.

Speaker #3: Importantly, Nictimbo is profitable to Syndax with our 50% share of the Nictimbo product contribution amounting to 13.9 million dollars for the third quarter. As sales continue to ramp, we expect the proportion of net revenue retained by Syndax to materially grow over time.

Speaker #3: We remain on the road to profitability with growing contributions from RevyForge and Nictimbo, a solid balance sheet, and an operating expense base that will remain stable over the next few years while fully funding our strategic priorities.

Speaker #3: Most notably, our strategic priorities include the expansion of RevyForge and Nictimbo into the frontline setting, which would unlock a combined market opportunity exceeding 10 billion dollars.

Speaker #3: Enrollment is well underway and has evolved, too. The first pivotal frontline trial for a Menon inhibitor has started enrolling patients. We have the right strategy and partnerships to flawlessly execute this trial and be the first to frontline with a Menon inhibitor.

Speaker #3: With Nictimbo, 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 and more detail.

Speaker #3: Steve.

Speaker #2: Thank you, Michael. Starting with RevyForge 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 MPM1 and our future expansion into the frontline setting.

Speaker #2: In the first 10 months of sales, we've generated nearly 90 million dollars in RevyForge net revenue, exceeding by a wide margin the launch benchmark set by other AML therapies.

Speaker #2: These impressive results reflect the rapid adoption of RevyForge as the standard of care in relapse, refractory KMT2A, and physicians' positive experience with the drug.

Speaker #2: Sales of RevyForge are strong in the third quarter with 32 million dollars in net revenue, up from 28.6 million dollars in the prior quarter.

Speaker #2: 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.

Speaker #2: This robust increase in demand speaks to RevyForge'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 a launch.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: The use of RevyForge 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 relapsed patients alone.

Speaker #2: Claims data is also showing significant combination use, with one-third of patients receiving RevyForge in combination with another standard of care therapy. Venetoclax being the most common.

Speaker #2: This trend highlights physicians' comfort with the RevyForge 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 RevyForge have proceeded to a stem cell transplant. We continue to see patients being put back on RevyForge by their physicians after a three- to four-month pause for engraftment.

Speaker #2: We estimate that 35 to 40% of transplant patients have restarted RevyForge, with that percentage expected to build over time as more patients clear the engraftment period and physicians gain more experience using RevyForge post-transplant.

Speaker #2: 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 RevyForge.

Speaker #2: As RevyForge 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.

Speaker #2: 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.

Speaker #2: Let's turn to MPM1, the next important growth driver for RevyForge. As shown on slide five, the second indication approved for RevyForge expands our annual total addressable US population from approximately 2,000 to 6,500 incident patients across both genetic subtypes in the relapse, refractory setting.

Speaker #2: A $2 billion-plus market opportunity. Moving to slide six. Our promotional expansion into MPM1 began quickly once we received approval on Friday, October 24th, with broad communication outreach to all relevant treatment centers and healthcare practitioners.

Speaker #2: 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.

Speaker #2: We are pleased with the early progress we have made, driving awareness of the expanded indication and generating demand in MPM1. Physicians are enthusiastic to have RevyForge as a new, effective, option for their MPM1 patients.

Speaker #2: Our success in MPM1 is going to be driven by two main factors. First, the breadth and strength of the RevyForge efficacy data and the overall product profile.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: Second, we have a solid commercial foundation that we're leveraging, including a large prescriber base that has already seen excellent clinical results with RevyForge and has experienced how easy we've made it for their patients to gain access to the drug.

Speaker #2: Physicians have already treated well over 1,000 patients with RevyForge 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 RevyForge on a regular basis.

Speaker #2: Physicians tell us it typically takes two or three patients to develop loyalty and habit with the new oncology medicine, and most of the major centers have already built up that comfort and muscle memory with RevyForge.

Speaker #2: 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 MPM1.

Speaker #2: The positive experience accounts have had with RevyForge 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.

Speaker #2: Our highly experienced customer engagement team has long-standing relationships with key prescribers. And accounts. Formula recovered for KMT2A is already in place. For 97% of covered lives and is expected to build rapidly for MPM1.

Speaker #2: While it builds, we expect the reimbursement rate to be high, given the NCCN guideline listing for MPM1 and the existing KMT2A coverage. We have everything we need for a successful expansion into MPM1 and look forward to providing further updates as this exciting launch progresses.

Speaker #2: Turning to Nictimvo on slide seven, we saw robust Nictimvo growth in the third quarter, with $45.8 million in net revenue, up 27% from the prior quarter.

Speaker #2: We continue to receive excellent feedback from HCPs on the rapid and durable improvements they are observing with Nictimvo, across some of the most difficult to treat organs associated with chronic GBHD.

Speaker #2: 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.

Speaker #2: Usage has been mostly in the fourth line, but it is growing in the third line, with the recent decrease in Reserox sales, corresponding with increased adoption of Nictimvo.

Speaker #2: Of the patients who started Nictimvo 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 US prescribing Nictimvo, with all centers placing repeat orders year to date.

Speaker #2: 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 US requiring three or more lines of therapy, representing a two billion dollar market opportunity as shown on slide eight.

Speaker #2: I'll close by saying that I'm thrilled by the progress we have made with RevyForge and Nictimvo. Both medicines are delivering for patients, and on blockbuster trajectories.

Speaker #2: 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.

Speaker #2: With that, I'll hand the call over to Nick to discuss our upcoming data presentations at ASH. Nick. It's a pleasure to be on the call today.

Speaker #2: Thank you, Steve. And to discuss the strong presence Syndax will have at ASH with 23 abstract accepted for presentation, including six oral presentations highlighting our scientific leadership in menin inhibition and CSF1R inhibition.

Speaker #2: Starting with RevyForge, or RevyMeniv, collectively the abstracts highlight the remarkable activity and tolerability of RevyMeniv in multiple genetic subtypes, both as a monotherapy and in combination with standard of care therapies across the acute leukemia treatment continuum.

Speaker #2: Slide nine. Summarizes the first real-world evidence for menin inhibitor. Data from the first 18 patients treated commercially with RevyForge at Moffitt Cancer Center show favorable tolerability and excellent clinical activity across multiple genetic subtypes and settings.

Speaker #2: Patients with MPM1, KMT2A, and NUC98 are acute leukemias are included in the data set. 15 patients received RevyForge in their last refractory setting. Two in the front line and one after stem cell transplant without prior RevyForge treatment.

Speaker #2: Notably, nearly 80% of the patients received RevyForge 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.

Speaker #2: Sixteen patients were efficacy evaluable. Among fourteen 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 MPM1 responders, respectively.

Speaker #2: Four patients, or 29% of the population, treated for morphological disease proceeded to a stem cell transplant. Three patients received RevyForge as maintenance post-transplant, including two who resumed RevyForge post-transplant and one who started post-transplant without prior RevyForge treatment.

Speaker #2: It's also noteworthy that there were two additional patients who were treated with RevyForge MPM1 MRD positivity. With one of the patients achieving MRD negativity at the data cutoff, the potential use of RevyMeniv as an MRD eraser in HOXMES-driven tumors is an area of high clinical interest, with multiple ongoing studies exploring this area.

Speaker #2: Importantly, RevyForge 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.

Speaker #2: There was a low rate of RevyMeniv dose reductions, and no AEs led to RevyMeniv discontinuation. DS and QTC were well managed with no events of either above grade three.

Speaker #2: The first real-world data set provides important insight into the breadth of RevyForge usage we are observing at leading academic institutions like Moffitt. The use in KMT2A, MPM1, and NUC98 underscores the clinical value of the data we have presented showing activity in multiple genetic subtypes.

Speaker #2: One of the several differentiating features of the RevyMeniv profile. The high rate of combination therapy observed highlights physicians' comfort with RevyMeniv safety profile and their desire to combine therapies with the hope of achieving deeper and more durable responses.

Speaker #2: 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.

Speaker #2: Turning to slide 10 on the front line setting. We are pleased to share data from the first 17 patients enrolled in the newly diagnosed cohort of the SAFE trial.

Speaker #2: This trial is evaluating RevyMeniv in combination with venetoclax and decitabine sedazuridine in the relapsed refractory and front line 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.

Speaker #2: Among newly diagnosed patients with MPM1 or KMT2A, 88% of evaluated patients achieved a CR, 100% of patients with CR were MRD negative by flow cytometry.

Speaker #2: Five patients, or 29%, proceeded to transplant. Two of these patients had resumed RevyMeniv 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.

Speaker #2: 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.

Speaker #2: This is an important data set that builds on the encouraging results observed in the BEAT AML trial of RevyMeniv with venetoclax and azacitidine in newly diagnosed patients with AML.

Speaker #2: The concordance of the results from two different studies and different centers bolsters our confidence in the potential for RevyMeniv in combination with low-intensity therapy to transform the treatment paradigm for newly diagnosed MPM1 or KMT2A AML.

Speaker #2: To realize the full therapeutic potential of RevyForge, we are laser-focused on advancing our front line trials including the pivotal Evolve2 trial of RevyMeniv with venezo, that was initiated in collaboration with Hovon in the first quarter of 2025.

Speaker #2: The first pivotal trial of the menin inhibitor to start enrolling in the front line setting. Moving now to slide 11. And preliminary, phase one data supporting RevyMeniv in combination with intensive chemotherapy, or seven plus three, in newly diagnosed patients with MPM1 or KMT2A AML.

Speaker #2: 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.

Speaker #2: Collectively, the early data from these trials show the tolerability of RevyMeniv in combination with seven plus three, along with high rates of CR, MRD negativity transplant, and rapid count recovery.

Speaker #2: Both trials evaluated two dose levels of RevyMeniv in combination with seven plus three induction and cytarabine consolidation. Those level one was RevyMeniv at 110 or 220 milligrams every 12 hours with or without strong CYP3A4 inhibitor, respectively.

Speaker #2: Those 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 RevyMeniv.

Speaker #2: 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 typhilitis, or severe inflammation of the intestine.

Speaker #2: 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 RevyMeniv appears to be well tolerated both as seven plus three induction and consolidation.

Speaker #2: In the Syndax study, one DLT of grade three QTc prolongation was reported at dose level one. This patient discontinued RevyMeniv 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.

Speaker #2: Turning to the promising clinical activity observed among nine efficacy-valuable MPM1 and KMT2A patients in the NCI trial at dose levels one and two at the time of the abstract data cutoff, 89% achieved a CR, and 44% proceeded to transplant following treatment with RevyMeniv.

Speaker #2: The median time to full count recovery, including both neutrophils and platelets, was 25.5 days among patients with CR. Among seven efficacy-valuable 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.

Speaker #2: 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 review program, which will evaluate RevyMeniv in combination with intensive chemotherapy in newly diagnosed FIT patients with MPM1 or KMT2A.

Speaker #2: We remain on track to initiate review 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 RevyMeniv we are observing in the post-transplant setting.

Speaker #2: In a retrospective review of 10 pediatric patients with KMT2A or NUP98R acute leukemia who received RevyMeniv maintenance post-transplant at MD Anderson, RevyMeniv was well tolerated with promising early efficacy.

Speaker #2: Patients received a median of two cycles of RevyMeniv prior to transplant, and RevyMeniv was initiated at a median of 111 days or roughly three to four months post-transplant, consistent with what we have observed in other data sets.

Speaker #2: The study planned for continuation of RevyMeniv post-transplant for up to one year. Patients had completed a median of 11 cycles post-transplant at the time of the data cutoff.

Speaker #2: One patient continued for two years due to parental preference. This highlights the tolerability of RevyForge and reinforces prior feedback we have received from patients and families on the strong desire to stay on therapy that induced remission.

Speaker #2: At the last follow-up, all 10 patients were alive, with no relapses, yielding an estimated one-year survival rate of 100%. These are very encouraging results in a population with a high risk of relapse within the first year.

Speaker #2: The use of RevyMeniv 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 RevyMeniv as post-transplant maintenance in adult and pediatric patients with MPM1 or KMT2A.

Speaker #2: This trial, which is actually actively recruiting at City of Hope and Dana-Farber Cancer Institute, is planning to continue RevyMeniv for two years post-transplant. Turning now to Axitillinab on slide 13, I will briefly highlight three Axitillinab abstracts that underscore the potential for long-term benefit in recurrent refractory chronic DVHD, and the feasibility of combining ruxolitinib in newly diagnosed chronic GVHD.

Speaker #2: The first abstract shows that 33 of the 239 patients in the pivotal Agave 201 trial of Axitillinab were still on therapy as of March 2025, with a median of 2.8 years on Axitillinab.

Speaker #2: Long-term data show a continued tolerable safety profile. The second abstract reports the safety and feasibility of Axitillinab 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.

Speaker #2: Among the 19 patients who switched, the four-week dosing was well tolerated with a median of 1.7 years on therapy after the dosing change. The third abstract reports interim safety data from 44 patients enrolled in the ongoing phase two trial of Axitillinab with ruxolitinib in newly diagnosed chronic GVHD.

Speaker #2: 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 Axitillinab into the frontline setting in combination with standard-of-care therapies.

Speaker #2: In summary, this year's ASH will be another exciting meeting for Syndax. After watching the clinical community's enthusiasm for RevyMeniv and Axitillinab 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.

Speaker #2: 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.

Speaker #2: I will touch on a few key points on slide 14. For the third quarter of 2025, we reported RevyForge net revenue of $32 million. Quarter-over-quarter sales growth was driven by demand, as inventory levels remained at two to three weeks.

Speaker #2: 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 RevyForge's gross to net adjustments in the third quarter, versus 2Q, while still within the 20 to 25% guidance range we previously provided.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: Looking ahead, we expect sales growth to meaningfully accelerate over the coming quarters, with the approval in MPM1 and an increasing average duration of therapy in KMT2A as more patients receive RevyForge, e, as long-term maintenance therapy post-transplant.

Speaker #2: Turning to Nictimvo, Syndax reported 13.9 million dollars in collaboration revenue, after deducting the cost of sales and commercial expenses. Importantly, Nictimvo continues to be positive cash flow contributor to Syndax.

Speaker #2: We continue to expect the Nictimvo margin contribution, defined as collaboration revenue recorded by Syndax, as a percentage of Nictimvo 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.

Speaker #2: We expect continued robust growth, given GVHD is a chronic disease, where there is a high response rate to Nictimvo, and the average patient will likely remain on therapy for years.

Speaker #2: Turning to balance sheet, we continue to maintain a strong financial position, with 456 million dollars in cash, equivalents, and short and long-term investments, as of September 30th.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: Our cash, combined with increasing RevyForge and Nictimvo cash flow contributions, alongside an expected fixed expense base, will drive our path to profitability. Michael?

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: With two exceptional product launches underway, a strong balance sheet, and stable expense outlook, we are on the road to profitability and fulfilling our mission as a company.

Speaker #1: 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.

Speaker #1: With that, I would like to open the call for questions. Operator?

Speaker #3: At this time, I would like to remind everyone that in order to ask a question, please press star, then the number five on your telephone keypad.

Speaker #3: 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.

Speaker #3: The first question is from Anupam Rama with JPMorgan. Your line is now open.

Speaker #4: Hi, guys. This is Priyanka An for Anupam. Can you review how RevyForge is placed 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?

Speaker #4: Would physicians with experience with RevyForge be more willing to use it in earlier lines of therapy? Thanks.

Speaker #1: Yeah, 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.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: 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.

Speaker #1: In our commercial experience, we've seen about a third go to transplant. So we've actually seen quite a shift, and that we think will manifest in patients staying on drug longer, over time, in KMT2A.

Speaker #1: So that's been very meaningful. We expect that with MPM1, these patients are getting to transplant as well. We're also seeing high rates of response.

Speaker #1: About half 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.

Speaker #1: So 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 MPM1, and ultimately should lead to better utilization and longer utilization for patients.

Speaker #3: Your next question will come from Corinne Johnson with Goldman Sachs.

Speaker #5: Good afternoon.

Speaker #3: Your line is now open.

Speaker #5: Good afternoon. 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?

Speaker #5: And when could that start to be reflected in the revenue trajectory? Thanks.

Speaker #1: 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 four to six months, and that was really reflective of new patients' starts and some patients coming back from on maintenance therapy post-transplant.

Speaker #1: 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.

Speaker #1: We expect obviously to have a launch now with MPM1, so additional patients will be receiving therapy. And then we'll have some of those patients go to transplant as well.

Speaker #1: 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 MPM1, that mix of patients will have a slightly longer duration of therapy.

Speaker #1: MPM1, 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 those some will.

Speaker #1: So it's the mix of those two patient populations that we believe will drive to 6 to 12 months in the second year.

Speaker #3: Your Your next question will come from Brad Camino with Guggenheim.

Speaker #6: 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 RevyMetib during the first few months of launch?

Speaker #6: Because obviously the 35 to 40% you're reporting is way down by the bolus of recent patients getting transplants but not yet undergoing the ability to get maintenance.

Speaker #6: So were you able to do a longitudinal analysis at all to understand where that restart rate number can grow to? Thank you.

Speaker #1: Excellent question, Brad. I think we've seen some progress this quarter in the restart rate where we saw last quarter about a third of patients restarting maintenance therapy.

Speaker #1: Now it's up to about 35 to 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.

Speaker #1: We do think that will build in the next quarter and the quarters beyond. We don't have an upper limit on what percentage of patients will come back.

Speaker #1: 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 it's hard to estimate what the upper limit is of what percentage of patients will come back.

Speaker #1: 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 the month therapy.

Speaker #1: 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.

Speaker #3: Your next question will come from Clara Dong with Jeffries.

Speaker #7: Good afternoon. Thanks for taking our questions. So as we think about the relationship between prescription growth and revenue growth, could you provide some perspective in terms of how revenue per prescription might evolve as a patient makes shifts from a predominantly KMT2A in the third quarter to include more MPM1 patients going forward?

Speaker #7: Thank you.

Speaker #1: Yeah, Keith, do you want to take that question?

Speaker #2: Yeah, Clara, thanks. Thanks for the question. We really don't expect much of a change in terms of average revenue per prescription as more and more MPM1 patients start to make their way into our prescribing base.

Speaker #3: Your next question will come from Peter Lawson with Barclays.

Speaker #1: Great. Thank you. Thanks for taking my questions. Just on the delta between quarter after quarter growth of registered versus the RX rate. Kind of in any way to break down that gap between growth versus inventory timing that we should be thinking about or any changes that we should be thinking about going forward?

Speaker #1: And then I've got a question just on if there's been any friction with getting MPM1 authorizations and payer access. Peter, thanks for the question regarding recorded growth and the breakdown between what we're seeing in those metrics.

Speaker #1: But Keith, why don't you take that question?

Speaker #2: Yeah, Peter, thank you. I'd start out by saying that generally when you see a disconnect in a quarterly result between net revenue and prescription growth, as is often the case, especially in launches, there's generally two factors.

Speaker #2: That play into that. And it's generally growth differences and growth to net in different differences in inventory stocking. And as I said, both can fluctuate quarter to quarter.

Speaker #2: In this period, as I said in my prepared remarks, the delta was primarily driven by higher growth to net adjustments. I want to emphasize it's still within the range we provided.

Speaker #2: So very tight range of 20 to 25%. But we did have slightly higher 340B chargebacks and slightly higher Medicaid and Medicare utilization. As I said, both remain within the guidance range.

Speaker #2: 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.

Speaker #2: But we did see a slight drawdown in inventory. Which those two factors combined to explain the disconnect between prescription growth of 25% and revenue growth of 12%.

Speaker #1: Yeah. And 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.

Speaker #1: And we had an offset of only about 35 to 40% of those patients coming back. So that'll build over time, but that was, of course, is a factor in what could have been a different quarter from a top-line perspective.

Speaker #2: Yeah, and the other part of Peter's question was just friction on a payer side. So as you know, payer access formulary coverage for RevyForge really since launch has been simply outstanding by month five.

Speaker #2: We hit 97% formulary coverage. So in essence, unfettered access for commercial part D and Medicaid patients. There is, of course, been some off-label prescriptions outside of KMT2A.

Speaker #2: We know that. It's been about 10% since launch. And that'll obviously the usage will grow with the indication. But we haven't had any pushback from payers for the most part.

Speaker #2: Even in advance of the MPM1 indication, once the publication came out in May in blood, obviously the NCCN listing was in the third week of September.

Speaker #2: That's really what payers need to get products covered. Even when they're not 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.

Speaker #2: Coverage will build quickly. But in the interim, Peter, as coverage builds, the claims will be adjudicated and paid for. So if patients will still enjoy open access to RevyForge moving forward until that coverage is permanent.

Speaker #3: Your next question will come from Ellen Horst with TD Cowan.

Speaker #8: Hi guys. Congrats on the quarter and all the exciting abstracts. Just wondering a couple of things about the MPM1 launch. One, if you notice any modest uptick in the final days of Q3 where you did have that inclusion in the NCCN guidelines.

Speaker #8: And then more broadly, wondering how we should think about the launch trajectory in the MPM1 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.

Speaker #8: Any thoughts there would be helpful. Thank you.

Speaker #1: Yeah, 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.

Speaker #1: So first, strong start to the quarter. I'd say HCPs are excited. As you can imagine, awareness is quite high. Increase in prescriptions we're seeing it.

Speaker #1: Accounts are ordering and have expanded. Set up 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.

Speaker #1: 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.

Speaker #1: And we talked about the factor as well. We'll drive KMT2A business, which is new patient starts, steady, as well as maintenance and patients coming back from onto maintenance therapy, which will grow.

Speaker #1: So we're expecting a good Q4. Maybe I'll turn it over to Steve to talk about launch trajectory MPM1.

Speaker #2: Yeah, 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.

Speaker #2: I think I mentioned in my prior comments. We're excited about the launch. I know physicians are as well. There's three main drivers as we think about this.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: 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 MPM1.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: And that experience accounts has is meaningful. It's really two to three patients to gain some serious muscle memory and use. And the last piece, which we highlighted in this call, is really the ongoing clinical development program.

Speaker #2: The data that we've been supporting in 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.

Speaker #2: So we feel we're in a great position moving forward.

Speaker #1: Yeah, thanks. And I would just add that I think we have it's quite simple. In terms of our view on competition, the RevyForge has the broadest and strongest efficacy profile.

Speaker #1: This is a very 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.

Speaker #1: And RevyForge 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.

Speaker #1: And we have a pretty simple view on how the competitive dynamic will play out. We should dominate this market.

Speaker #3: Your next question will come from Steven Wiley with Stifel.

Speaker #9: Yeah, good afternoon. Thanks for taking the question. Just one, I guess, on the soon-to-initiate reveal trial. And frontline patients with intensive chemo. I know we don't have protocol details yet, but I was just curious about how your philosophically thinking about specifically evaluating the contribution of maintenance therapy within the protocol itself.

Speaker #9: 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.

Speaker #9: Thanks.

Speaker #1: 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.

Speaker #1: So maybe I'll turn it over to Nick to take that.

Speaker #10: 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.

Speaker #10: This quarter, and 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.

Speaker #10: 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.

Speaker #10: 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.

Speaker #10: 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 our use in the maintenance setting in the frontline.

Speaker #3: Your next question will come from Migal Nakamovitz with Citigroup.

Speaker #4: Hi, thanks for taking the questions. 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?

Speaker #1: Migal, 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?

Speaker #2: Yeah, so we know there's usage across academia as well as the community. The majority is in academics, and these patients are very sick. That's not uncommon.

Speaker #2: Whether it's for KMT2A, we expect that early for MPM1. So the majority has been in academia. We're not able to peel apart the rates the treatment rates and maintenance.

Speaker #2: 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.

Speaker #2: But for now, the rates we've shared are really across the spectrum.

Speaker #4: Okay, thanks. And I know you mentioned, obviously for MPM1, you'll have fewer 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 MPM1 could still get RevyForge as maintenance, even if they didn't get it before?

Speaker #4: Or that wouldn't happen?

Speaker #1: Excellent question, Migal. I'll turn it over to Nick.

Speaker #10: Actually, yes, interestingly, we are seeing that. In fact, there was a reported case in the real-world series that I mentioned from Moffatt. You'll see one patient actually started on RevyForge, having assumed as a function of timing, not had treatment prior to their transplant.

Speaker #10: So there is now, and we've heard from some other centers as well, that there is a desire if they haven't had RevyForge prior to the transplant, that they would start on it as a maintenance therapy afterwards.

Speaker #4: Oh, very interesting. Okay, thank you.

Speaker #1: Yeah, thanks for the question, Migal.

Speaker #3: Your next question will come from Justin Zelin with BCIG.

Speaker #1: Thanks for taking the question, and 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.

Speaker #1: Do you see patients discontinuing the drug at all for any adverse events? Thank you. Justin, thanks. I'm going to turn it to Nick for safety profile.

Speaker #10: 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.

Speaker #10: Again, we've talked about being 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.

Speaker #10: So it's very well managed. We actually see, as you can see from the data with the extensive data we're going to be presented at ASH, you see very low rates of discontinuations from therapy.

Speaker #10: 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.

Speaker #3: Your next question will come from Salim Syed with Mizuha.

Speaker #11: 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 that's now listed in the black box there.

Speaker #11: I know it's one case, and you mentioned previously you don't expect things to really change. With that, 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?

Speaker #11: 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.

Speaker #11: Thank you.

Speaker #1: And Nick, do you want to?

Speaker #4: 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 maybe being sent to newly diagnosed.

Speaker #4: 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.

Speaker #4: There'll be a control arm. It'll be much easier to ascertain the true rates of drug-related side effects with the control. So I think it'll be much more informed.

Speaker #4: And based on what we've seen today, we're really seeing very low rates of serious cardiac events or discontinuations.

Speaker #1: 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.

Speaker #1: And here's the takeaway. I mean, they're excited about the profile. RevyForge'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.

Speaker #1: 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. They've also treated MPM1 patients successfully during this time.

Speaker #1: 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.

Speaker #1: So that's really where we leave things.

Speaker #11: Okay, thanks, Mike. Thanks, Nick.

Speaker #1: Thanks.

Speaker #3: Your next question will come from David Day with UBS.

Speaker #11: Thanks for taking my questions. Just a question on the 35 to 40% patients who resumed RevyForge post-transplantation. Third quarter, could you maybe provide some additional detail around the timing of the maintenance use?

Speaker #11: How long is the drug holiday before we'll see them coming back to the maintenance therapy?

Speaker #1: 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.

Speaker #1: For the ones who go to transplant, they usually get their response in that timeframe. They go to transplant, so they're off of RevyForge. For a period of time, and then they resume about three to four months later.

Speaker #1: So it's call it six in the range of six months from start to resumption of therapy in the maintenance setting.

Speaker #3: Your next question will come from Mayank Mamthani with BeeRiley.

Speaker #4: Yes, good afternoon, Dean. Thanks for the question, and congrats on strong momentum. Actually, a lot of demand indicators align with our recent physician survey.

Speaker #4: 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 to be a bit more dominant from a timing standpoint?

Speaker #4: 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.

Speaker #4: Then I have a quick follow-up.

Speaker #1: 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.

Speaker #1: 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 group of patients a growing group of patients in KMT2A going to transplant and then coming back on for maintenance.

Speaker #1: NPM1, we'll have its own dynamics. But we do have the best profile, we believe, in both those segments where widely indicated for AML/ALL for KMT2A adults and pediatrics.

Speaker #1: 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.

Speaker #1: So, 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 majority share in both segments.

Speaker #4: Okay. And on the impressive frontline AML dataset from the Save All Oral Regimen, I believe that was, and then the intensive chemo combination we also saw a couple of peer frontline datasets that were released this morning.

Speaker #4: 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?

Speaker #4: And the post-transplant one-year relapse-free 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?

Speaker #4: Thanks for taking your questions.

Speaker #1: Yeah, great questions, Nick. I'm going to turn it over to Nick to maybe address each of those if he can.

Speaker #4: Yeah, I'd 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.

Speaker #4: And as you say, very compelling data in the frontline setting from both our Save All Oral data, but also now our emerging data from intensive chemotherapy, which we will be updating.

Speaker #4: 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.

Speaker #4: I think the overall 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.

Speaker #4: Where we're seeing 100% response rate and 100% MRD negativity in what we've reported, it's really quite unparalleled. Again, it speaks to the depths of the breadth of the profile that we see with Revumenib.

Speaker #4: 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 Veneza, 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.

Speaker #4: And has been enrolling since earlier this year. So, yeah, 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.

Speaker #4: Thank you. Look forward to seeing you in Orlando.

Speaker #1: Wonderful. Thank you so much. Us as well.

Speaker #3: Our final question today is from the line of Jason Szymanski with Bank of America.

Speaker #5: 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 in early next year.

Speaker #5: 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.

Speaker #5: And then I guess secondarily, if a patient returns to RevyForge 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?

Speaker #5: Thanks.

Speaker #1: Jason, thanks for the questions. First question, impact of GTN for NPM1. Keith, I'll address that.

Speaker #4: Yeah, 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.

Speaker #4: So it's based on a trailing period of demand. So we expect inventory levels in our specialty distribution channel to stay at two to three weeks.

Speaker #4: 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.

Speaker #4: 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.

Speaker #1: Steve, you want to take the second question?

Speaker #2: Yeah, and maybe just a comment on the gross to net. I mean, NPM1 patients tend to be older, so Keith, you're at the mix.

Speaker #2: 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.

Speaker #2: There has 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 of the drug brings.

Speaker #2: They've accepted the price so a vast majority of prescriptions are being paid for regardless of if there are KMT2A, NPM1, maintenance, or even for other off-label use.

Speaker #2: So we don't expect any pushback from payers on patients returning to a maintenance therapy.

Speaker #5: Great. Thanks for the color.

Speaker #1: Thank you, Jason.

Speaker #3: This concludes our question and answer session. I will now turn the floor over to Mr. Michael Metzger for any closing remarks.

Speaker #1: 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, Jeffries, and Encore conferences evercore conferences.