Syndax Pharmaceuticals - Q3 2024
November 5, 2024
Transcript
Operator (participant)
Good day, everyone, and welcome to the Syndax Third Quarter 2024 earnings conference call. Today's call is being recorded. All participants have been placed in a listen-only mode. You'll have an opportunity to ask questions after today's presentation. If you'd like to ask a question, please press star five on your telephone keypad to be placed in the queue. You may also press star five again to remove yourself from the queue. At this time, I'd like to turn over the call to Sharon Clary, Head of Investor Relations at Syndax Pharmaceuticals.
Sharon Klahre (Head of Investor Relations)
Great. Thank you, Operator. Welcome, and thank you all for joining us today as we review Syndax's Third Quarter 2024 financial and operating results. I'm Sharon Clary, and with me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer, Dr. Neil Gallagher, President and Head of R&D, Steve Kloster, Chief Commercial 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 Ganguly, 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.
Before we begin, I'd like to remind you that any statements made during the call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, November 5th, 2024 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.
Michael Metzger (CEO)
Thank you, Sharon. Good afternoon, everyone, and thank you for joining us today. We made remarkable progress in the third quarter. We delivered on multiple important milestones that demonstrate our ability to bring novel medicines to patients, and in doing so, we marked our transition from a development organization to an integrated commercial-stage company with an extremely bright future. With the announcement of yesterday's $350 million royalty agreement for Niktimvo with Royalty Pharma, we have strengthened our balance sheet significantly and now have the capital to fund Syndax through profitability, ensuring strong launches for revumenib and Niktimvo and solidifying our commitment to their continued development and expansion of the pipeline overall. Importantly, this deal further highlights how vastly underappreciated the value of Niktimvo is in the market and why it remains a critical element of our long-term strategy. Let me now dig into some third-quarter milestones.
In August, we received FDA approval for Niktimvo, the first and only CSF1R antibody approved for the treatment of chronic graft-versus-host disease, or GVHD, after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kilograms. Shortly after we received FDA approval, the positive pivotal AGAVE-201 trial results were published in the New England Journal of Medicine, and Niktimvo was added to the latest NCCN Guidelines, two achievements that highlight the significance of this dataset and the important role of Niktimvo in the treatment armamentarium. With Incyte's deep understanding of the GVHD market and long-standing relationships with key stakeholders, we are thrilled to partner with them to bring this much-needed new option to patients. Later in the call, Steve will provide more color on our plans for the commercial launch.
We believe the approval of Niktimvo represents the initial opportunity to make a major impact for patients by targeting the CSF1R pathway. Together with Incyte, we are advancing a robust clinical development program, investigating the potential for Niktimvo in frontline chronic GVHD in combination with standard-of-care therapies and in other diseases marked by fibrosis and inflammation, such as idiopathic pulmonary fibrosis, or IPF. In addition to making tremendous progress with Niktimvo, we've also continued to make excellent progress advancing revumenib, our selective menin inhibitor that we anticipate will receive FDA approval this quarter in relapsed or refractory KMT2A rearranged acute leukemia. With a PDUFA date of December 26, 2024, and compelling clinical data across the treatment continuum, we believe revumenib is poised to become first-in-class and practice-changing therapy for KMT2A and NPM1 acute leukemia.
In addition to the anticipated approval of revumenib, we are also looking forward to the top-line readout from the pivotal cohort of patients with mutant NPM1 AML, our AUGMENT-101 trial this quarter. In the recent months, we've executed on multiple initiatives that we believe lay the foundation for a strong revumenib launch and successful long-term franchise growth across both KMT2A rearranged and mutant NPM1 acute leukemias. In September, we published the pivotal data from the AUGMENT-101 trial supporting the use of revumenib in relapsed or refractory KMT2A rearranged acute leukemia in the Journal of Clinical Oncology. This publication is raising awareness of revumenib's compelling profile and potential utility once approved and will be instrumental in gaining rapid acceptance into the NCCN guidelines.
As you saw from our press release earlier today, we have multiple presentations at ASH that highlight the clinical data supporting our two assets, including additional revumenib data in KMT2A rearranged acute leukemia from the phase II portion of our AUGMENT-101 trial and new combination data from the investigator-sponsored SAVE trial. These data, which are consistent with our previously reported data, continue to show remarkable responses that are deep and durable in heavily pretreated patients. Furthermore, in both monotherapy and combination, revumenib continues to demonstrate a tolerability profile that allows patients to benefit significantly from continued therapy. Beyond the conference presentations, we will also have the opportunity to discuss the latest data supporting our pipeline at ASH and our event on Monday, December 9th.
And with that, I'm going to turn the call over to Neil to review the latest data in the ASH abstracts and review our revumenib clinical development program. Neil?
Neil Gallagher (President and Head of R&D)
Thanks, Michael. It's a pleasure to be with you all today to discuss the latest data emerging from our robust clinical development program investigating revumenib across the treatment continuum in both adults and pediatric patients with KMT2A rearrangements or mutant NPM1 acute leukemias. Through a thoughtful combination of Syndax-sponsored and investigator-sponsored trials, we're rapidly generating data supporting the use of revumenib both as monotherapy and in combination with standards of care, both in the frontline or relapsed refractory settings. On the next few slides, I'll review the recently released ASH abstracts that contain the latest data from a number of ongoing trials and briefly review the revumenib clinical development program. Turn to slide four. At ASH, we will be presenting an updated analysis that includes additional patients enrolled in the pivotal phase two portion of the AUGMENT-101 trial of revumenib in patients with relapsed or refractory KMT2A rearranged acute leukemia.
These new data are highly consistent with what was previously reported, with the previously reported data, rather, that form the basis of our NDA application. With a February 2024 data cutoff, the updated safety population comprises 116 patients, 22 more than in the original analysis, and the efficacy population has expanded to a total of 97, 40 more than in the original analysis. The median age is 35, and 24% of the population was under the age of 18. The median number of prior therapies was two, with 44% of the population having received three or more prior treatments. 63% had prior exposure to a venetoclax and 51% underwent prior stem cell transplant.
The efficacy results from this expanded analysis are highly consistent with what was previously reported from the interim analysis, with an overall response rate of 64%, a CR/CRh rate of 23%, and a composite complete remission rate of 42%. 21 of the 62 responders, or 34%, went on to receive allogeneic stem cell transplant, and nine patients resumed revumenib as maintenance therapy following transplant. The median duration of CR/CRh was 6.4 months at the time of the data cutoff. Among patients who are evaluable, 61% of CR/CRh and 58% of patients with CRc achieved MRD negativity. Achieving MRD negativity, or the absence of detectable leukemic cells, is an important clinical milestone as it may correlate with improved long-term outcomes. The consistently high rates of MRD negative status achieved with revumenib are indicative of its best-in-class potential.
Revumenib continues to be generally well tolerated, with only 5% of patients discontinuing treatment due to a treatment-related adverse event. The frequency and severity of AEs were consistent with previous reports. Moving to slide five, the updated analysis also includes an assessment of the durability of response among the 13 patients who achieved CR/CRh in the previously reported interim analysis that was presented at ASH in 2023. At the time of that analysis, the median duration was 6.4 months. In this updated analysis, with seven additional months of follow-up, the updated median duration has extended to 13 months. At the time of the most recent data cutoff, five of the 13 patients remained in follow-up without relapse. Moving to slide six, SAVE is an investigator-sponsore Phase Ib trial conducted by Dr. Issa at the MD Anderson Cancer Center.
The trial is evaluating an all-oral combination of revumenib, venetoclax, and oral decitabine in children and adults with relapsed or refractory AML or mixed lineage acute leukemias. As you may recall, at last year's ASH meeting, Dr. Issa presented promising data from the first nine patients enrolled in the trial. This new abstract includes data from 26 patients with a median age of 35. 42% of the patients had KMT2A rearrangements, 38% had mutant NPM1, and 20% had NUP98 rearrangements. Patients had received a median of three prior lines of therapy, including 65% who received prior venetoclax and 42% who had prior stem cell transplant. The combination was well tolerated with a safety profile similar to what is expected for venetoclax and hypomethylating agents alone. As you can see on the right-hand side of the slide, the all-oral combination showed promising results.
It is of note that two-thirds of these patients failed prior therapy with venetoclax. The overall response rate was 88%, with a CR rate of 46% and a CRh rate of 12%. Among the MRD evaluable patients with CR/CRh, 13 of 14 patients, or 93%, were MRD negative. 12 patients, or 46%, proceeded to stem cell transplant, with three patients resuming revumenib following transplant. With a median follow-up of 6.4 months, the six-month relapse-free survival was 59%, and overall survival was 74%. The median duration of CR/CRh was not reached. As of the data cutoff, two patients have completed maintenance post-stem cell transplant and remain in remission. These data, which further support the combinability of revumenib with venetoclax and hypomethylating agents, are encouraging. We look forward to sharing further data from this trial and new cohorts, including from a frontline cohort that is now enrolling.
Turning to slide seven, the two trials that I just reviewed are important parts of our comprehensive clinical development program evaluating revumenib across the treatment continuum. In addition to the trials just described, there will be an oral presentation at ASH on preliminary results from INTERCEPT, an investigator-sponsored platform trial led by the Australasian Leukemia and Lymphoma Group. This trial is evaluating novel therapies, including revumenib, to target measurable residual disease or early relapse in patients with AML. Patients are enrolled in remission, and their MRD status is monitored. Patients who become MRD positive or experience early relapse are then allocated to treatment. As of the data cutoff, nine patients with MRD relapse, including eight with mutant NPM1, one with KMT2A, and one with KMT2A rearranged AML, were enrolled in the safety cohort and received revumenib. Three patients had prior venetoclax exposure, and six had prior intensive chemotherapy.
The preliminary data from mutant NPM1 patients treated with revumenib are promising, with five of eight patients achieving a reduction in measurable residual disease, including three who achieved MRD negativity within six cycles. We look forward to seeing further data from this trial. BEAT-AML is another ongoing investigator-sponsored trial that is being conducted by the Leukemia and Lymphoma Society. This trial is evaluating the combination of revumenib with venetoclax and azacitidine in frontline patients with NPM1 or KMT2A-r AML. Data from the trial were recently presented from the European Hematology Association meeting in June. The CR/CRh rate was 96%. We are looking forward to the next anticipated update in the fourth quarter of 2024. Data from this trial have informed the design of the pivotal frontline phase III that we expect to initiate by the end of this year.
Moving to slide eight, you can see a high-level overview of this phase III trial design. The design of the pivotal frontline trial of revumenib in combination with venetoclax and azacitidine, or VenAza, in newly diagnosed adults with mutant NPM1 or KMT2A AML who are considered ineligible for intensive chemotherapy. This will be a randomized double-blind placebo-controlled trial conducted in partnership with the HOVON network. We're delighted to partner with HOVON. The group has conducted many robust phase III trials in AML over the last several decades. Syndax and HOVON have a shared commitment to improving outcomes for patients with AML, and therefore the partnership is a robust one. As I mentioned, we're very pleased to be partnering with the group. The trial will enroll approximately 400 patients randomized one-to-one to receive placebo plus VenAza or revumenib plus VenAza.
The primary endpoint is overall survival in patients with mutant NPM1 AML. Secondary endpoints include event-free survival, rate of CR/CRh, and rates of response without MRD. We expect the first site to be opened for enrollment by year-end. Turning to slide nine, ahead of our top-line readout from the phase II cohorts of patients with relapsed or refractory mutant NPM1 AML from AUGMENT-101, I wanted to briefly review the unmet need of these patients. Mutations in nucleophosmin 1 gene are the most common genetic alterations in AML occurring in approximately 30% of adults with the disease. While NPM1 mutations can be associated with favorable outcomes in certain frontline populations, the outcomes for patients who have relapsed or were refractory to therapy remain poor, with expected median overall survival of approximately six months or less after three or more lines of therapy.
As compared to patients with other genetic alterations such as KMT2A rearrangements, patients with NPM1 AML tend to be older and less fit to, for instance, receive intensive chemotherapy and proceed to transplant. In the phase I trial of revumenib in patients with relapsed refractory mutant NPM1 AML, a robust response rate was observed. Overall, the efficacy and safety profile in those patients was highly consistent with what has been observed in KMT2A-R patients. Based on historical approvals of other AML therapies, we believe that a CR/CRh rate of 20%-30% with a median duration of response in the four- to six-month range would represent a clinically meaningful improvement over the current standard of care and therefore potentially support regulatory approval. We look forward to reporting top-line data from the ongoing NPM1 cohort in AUGMENT-101 later this quarter.
So with that, I'm going to hand it over to Steve, who can tell us about progress on the commercial front. Steve?
Steve Kloster (Chief Commercial Officer)
Yeah, thank you, Neil. Starting with slide 10, we are thrilled that Niktimvo is now FDA-approved and included in the latest NCCN guidelines as a recommended treatment for chronic GVHD after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kilograms. We anticipate that this new medicine will be available to patients no later than early in the first quarter of 2025. Addressing the needs of patients who have progressed after at least two prior lines of therapy is an attractive commercial opportunity. For example, in the three years since the launch of belumosudil or Rezurock, another drug indicated for the same line of treatment as Niktimvo, net sales continue to grow in the high double digits and suggest that the drug is now annualizing at over $500 million in U.S. sales alone.
With the new mechanism and clinical data showing that Niktimvo can provide both rapid and durable responses in heavily pretreated patients, including results in difficult-to-treat organs, we believe that we will be able to capture a significant portion of the $1.5-$2 billion estimated total addressable market for third-line or later chronic GVHD treatment in the U.S. This will be a targeted launch as there are roughly 200 important transplant centers in the U.S. The Syndax team will provide 30% of the sales effort for Niktimvo, and our partner Incyte will provide 70%, leveraging their existing field force that is already deeply engaged with the chronic GVHD community through their work with Jakafi. The key transplant centers that we will be targeting fall squarely within the larger group of accounts that are also important for revumenib, creating opportunities for commercial synergy.
In addition to preparing for the launch of Niktimvo, we and Incyte are also continuing to advance clinical trials evaluating Niktimvo in earlier lines of chronic GVHD treatment and other diseases. Incyte is now enrolling patients in a phase II trial of Niktimvo in combination with Jakafi in patients with newly diagnosed chronic GVHD, and we continue to enroll patients in a phase II trial on top of standard of care in IPF with top-line data expected from that trial in 2026. Turning to slide 11, revumenib has the opportunity to transform the treatment paradigm for certain genetically defined acute leukemia patients who currently have no targeted options. There are several important factors that differentiate our program and position Syndax to establish a successful menin franchise. First, we're set up to secure first-mover advantage.
We have built a highly experienced commercial organization that is already engaging with key stakeholders and is ready to launch revumenib as soon as we receive the anticipated FDA approval before the end of the year in relapsed or refractory KMT2A rearranged acute leukemia. We believe that physicians' familiarity with revumenib will expand quickly because patients with these alterations have an urgent need for new treatment options as no drugs are currently approved for this population or under investigation in late-stage trials. With today's standard of care therapies, the median overall survival for patients who have received more than two prior lines of treatment is less than two and a half months, a truly devastating prognosis for patients. Given this is a high-risk population, centers are already routinely testing for KMT2A rearrangements.
Further, with compelling data across both KMT2A and NPM1 alterations, as well as adults and pediatrics, we expect to have a broad future label that drives a strong competitive advantage. Last but not least, we have a near-term opportunity for a unique launch trajectory with pivotal top-line data in relapsed or refractory mutant NPM1 AML expected in the same quarter as our anticipated FDA approval in KMT2A. Positive data would enable us to file a supplemental NDA in the first half of 2025, and if approved, we'd be positioned to launch into a second indication leveraging an already established commercial effort. We estimate that the two distinct market segments in acute leukemias, KMT2A and NPM1, equal a combined accessible population of 5,000-6,500 patients in the relapsed or refractory setting and an addressable market opportunity that approaches $2 billion in the U.S.
In summary, I'm very excited about positively impacting the lives of patients and the commercial opportunities we have with Niktimvo and revumenib. I'm confident that we are well prepared to successfully launch both of these drugs. With that, I'll pass the call to Keith to talk about our financials.
Keith Goldan (CFO)
Thanks, Steve. Turning to slide 12, we expect that the $399.6 million in cash equivalents and short and long-term investments on our balance sheet as of September 30th, plus the $350 million in cash received from the royalty funding agreement for Niktimvo, will provide sufficient cash for Syndax to reach profitability. Under the terms of the royalty funding agreement, Syndax received $350 million in exchange for a 13.8% royalty on U.S. net sales of Niktimvo. Royalty payments to Royalty Pharma are capped, which preserves the upside longer term for opportunities, including treatment of frontline chronic GVHD and IPF. Our financial strength allows us to fund the commercialization of Niktimvo, as well as the anticipated launch of revumenib, while also appropriately investing in our pipeline to fuel continued growth and value creation.
Turning to the income statement, operating expenses in the third quarter were $102.1 million and included $71 million of research and development expense and $31.1 million of selling general and administrative expense. For the full year of 2024, the company is narrowing its guidance and now expects research and development expenses to be $245-$250 million and total expenses to be $365-$370 million. Note that the guidance range for operating expense for the full year 2024 includes an estimated $41 million of non-cash stock compensation expense, which is down from a previously estimated $43 million, and that research and development expense guidance includes any milestones earned or expected to be earned by our partners upon potential approvals. With that, let me now turn the call back over to Mike.
Michael Metzger (CEO)
Thank you, Keith. As you heard today, we have built remarkable momentum heading into another exciting period filled with several near-term value-generating milestones that could be seen on slide 13. Building on the FDA approval of our first novel medicine in August, we are confident that revumenib will also be approved this year and launched soon thereafter. We believe this first anticipated approval in relapsed or refractory KMT2A rearranged acute leukemia will be just the first of several potential approved indications for revumenib, and we are extremely focused on leveraging our first-mover advantage to build long-term franchise value. This quarter, we will be presenting the first pivotal NPM1 dataset, which gives us the opportunity to further solidify our position in the emerging menin space. So stay tuned.
Finally, I want to take a moment to thank our dedicated Syndax team, collaborators, and most importantly, the patients, families, investigators, and trial sites who have participated in our clinical trials and made it possible for us to advance our mission. I'd also like to thank our committed long-term investors who continue to share in our mission and support our work building Syndax into a leading oncology company. And with that, I'd like to open the call for questions. Thank you, Operator.
Operator (participant)
At this time, I'd like to remind everyone in order to ask a question, please press star, then the number five on your telephone keypad. If you'd 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 will come from Anupam Rama with JPMorgan. Your line is now open.
Hi guys, this is Priyanka Grover for Anupam. Just a quick question from us. Post the potential approval of KMT2A and pending positive NPM1 data for revumenib, can you remind us of the process to get into guidelines and potential timeline considerations we should be thinking about?
Michael Metzger (CEO)
Sure. Thanks for your question, Priyanka. So the timing to get the guidelines or get into the guidelines, first you have to obviously have an approved drug, and then you have to have data that you can publish. So you publish the data and move quickly to do so, and that's our plan. And then ultimately, we all submit for guidelines. The NCCN guideline panels meet probably twice a year, but they do it on an ad hoc basis as well. So there's the opportunity for important approvals, as we would expect these to be, to be engaged and brought into the guidelines pretty expeditiously. And we did actually experience that with axatilimab. If you recall, we had approval and we had contemporaneous publication of that data in the New England Journal, as I mentioned in my remarks.
Then we were into, within two to three weeks, we were into the guidelines. That is all very much the plan to move as quickly as possible to move into guidelines.
Thank you so much for answering my question.
Thank you.
Operator (participant)
The next question will come from the line of Brad Canino with Stifel. Your line is now open.
Brad Canino (Analyst)
Thank you. Lots to talk about, and I look forward to asking more at ASH, but two topics for me for now. For AUGMENT-101, in the updated data, you noted nine of 21 or 43% of transplanted patients restarted revumenib maintenance. Is that a maintenance percentage rate you expect in the commercial setting, or could it be higher? And also, what have you seen so far on durations? And then congratulations on the HOVON collaboration for frontline AML. I think you do point to BEAT-AML updates in 4Q24. Help us understand what you're looking for in those data to finalize and initiate that pivotal trial. Thank you.
Michael Metzger (CEO)
Yeah, thank you, Brad. So maybe I'll take the first question and then I'll pass it over on the BEAT-AML trial to Neil. So in terms of the AUGMENT-101 trial, we did note that there were certain patients that went back on maintenance. And that is a trial-driven result. Physicians were allowed to put their patients back on therapy post-engraftment, and many physicians elected to do so. We do expect that phenomenon will continue to advance once the drug's approved and we'll have the opportunity to have many more patients treated. And of course, that would lead to potentially the opportunity to have patients not only go to transplant, but get back on therapy and stay on therapy for an extended period of time.
So I think we'll continue to build the data in the real world, but we are encouraged by what we've seen thus far in AUGMENT-101 in that regard. And then BEAT-AML, I think I'll turn it over to Neil in terms of what we expect on an update.
Neil Gallagher (President and Head of R&D)
Sure. Thanks, Brad. So what I think everyone should expect is more patients, right? Specifically, more patients treated at dose level one. So the combination of 113 milligrams of revumenib with venetoclax and azacitidine and some more patients also compared to what was previously reported. One thing, just a point of clarification, that is not rate limiting for us. We're currently actually applying for a health authority agreement or health authority approval to initiate the study. And that's why we remain on track to potentially initiate the phase III study by the end of the year. So those things are actually moving in parallel.
Brad Canino (Analyst)
Thank you.
Michael Metzger (CEO)
Thank you, Brad.
Operator (participant)
The next question is from the line of Peter Lawson with Barclays. Your line is now open.
Peter Lawson (Analyst)
Okay. Thank you so much. Just with the sale of some of the royalty stream from Niktimvo, does that accelerate any programs under development?
Michael Metzger (CEO)
So Peter, I think the setup with the royalty agreement, which was extremely positive for us, does, of course, bring in $350 million of cash onto the balance sheet. And pro forma, we land us at somewhere around $800 million. So I think we have a very strong balance sheet of which to execute on. I think we're set up extremely well for all the trial initiations that we have planned for frontline trials, pivotal trials, several additional trials we haven't named yet, but that will be in support of the utilization of our drug in other settings. So I think it definitely helps us aggressively move forward with plans for revumenib and for axatilimab, Niktimvo. So it really advances the portfolio overall and gives us the opportunity to expand the portfolio with other molecules as well. So it's a very, very happy, very healthy balance sheet.
Pro forma, I think I said approaching 800, it's about 750, actually. Just to correct myself. Thank you, Brad. Thank you, Peter.
Peter Lawson (Analyst)
And then the timing of the NPM1 data, is that before or after a publication? How we should be thinking about that and kind of if it's direct to NCCN guidelines or you're kind of thinking supplemental?
Michael Metzger (CEO)
Right. So I think the order of events here, you get approval on your molecule. We'll have obviously pivotal data within that same timeframe on NPM1. You need to publish that data for NPM1. The KMT2A data is already published. So we could get into guidelines for KMT2A upon approval. But for NPM1, you publish that data and then you submit it to guidelines. It moves independently of approval. So you could, and the plan would be to move as quickly as we can to get it into guidelines. And that would most likely precede approval on NPM1.
Peter Lawson (Analyst)
Gotcha. Okay. Perfect. Thanks so much.
Michael Metzger (CEO)
Thank you.
Operator (participant)
The next question is from the line of Chris Shibutani with Goldman Sachs. Your line is now open.
Chris Shibutani (Analyst)
Great. Thank you very much. I think many of us are beginning to turn to 2025, and I realize that with important data readouts coming out, that's a factor, but can you give us any sense early in terms of how we should be thinking about the trajectory of an initial commercialization of Niktimvo and what we can think about how the results from the NPM1 data may impact the level of spending that you have, particularly from the SG&A start aspect? Thank you.
Michael Metzger (CEO)
Great. Thanks so much, Chris. So maybe I'll turn it over to Steve to talk a little bit about, as you say, the early launch trajectory and that question related to 2025.
Steve Kloster (Chief Commercial Officer)
Yeah. So good question. Chris, I think in terms of trajectory, I think is the market ready and is there unmet need? And I think the answer is yes. We've seen a real growing market. Very encouraging if you looked at the latest sales for Rezurock, which I mentioned in my comments. It's a drug that's annualizing well over $500 million a year. It's in its third year of promotion. Any of the market research we've done suggests that patients are somewhat happy with treatment, but many are dissatisfied. So we know there's a need. The second piece I'd say is just preparedness. So we've had a little extra time to get prepared. We're lucky that we're partnered with Incyte. They've essentially built this market. They're in market now and calling on all the important customers. I mentioned there's a little over 200 transplant centers in the country.
We know that 35 of them generate half of the patient volume. They're already there profiling, so it's a small targeted group. They're already there. We'll obviously add some effort, and everything is in place to pull this product through at launch. There's, we'll say, a small bolus of patients that are always looking for something new. We may see those come into the market immediately after that, and we think we've got a great molecule that's got some real compelling attributes that we think we know will resonate with clinicians, and we're ready once we were able to press go to pull through them.
Michael Metzger (CEO)
Right, and so maybe you want to make a comment on revumenib as well?
Steve Kloster (Chief Commercial Officer)
Yes. And on revumenib, I think we're in the same place in terms of the trajectory. We've had the gift of time. We've had a little bit of delay. And I think what that's enabled us to do from a preparedness standpoint is be ready. The market's ready. We've been able to focus on menin inhibition as a mechanism of disease. The awareness is high. We've got a very talented team that's been put in place. They started calling the customers back in the June timeframe. We've got about 2,000 accounts that we call on for revumenib. There's about 200 that cover two-thirds of the patient opportunity. We've prioritized them. So we've taken a very talented, experienced sales team. It's got over 20 years in the space. Many of them have launched products. Average is about six. They came in with pre-existing relationships.
So we know a lot about our accounts and how they think about AML and ALL, where the role that KMT2A will play. Testing is very high. We're understanding how to pull things through. And then on the payer side, we've been calling on customers for well over a year. So the goal is to get onto formulary as close to approval as we can. Generally takes about nine to 12 months. With all the activity we've placed against payers, we think we can truncate that to a six to nine-month frame. We've also got a really great group of specialty pharmacies and distributors in place that are the best at what they do. So they'll be able to pull through prescriptions really at launch, getting through the medical exception process. So I think for that drug, there's not much of a bolus. Patients are too sick.
I think I mentioned the prognosis for patients with relapse refractory KMT2A-r is about two and a half months, and customers are incredibly eager for this drug to get approved, and we think once the drug is available, we'll get some immediate utilization.
Michael Metzger (CEO)
Then, Chris, this is Keith with respect to your question on SG&A spending. As Steve just pointed out, we are fully built from a commercial perspective. So I think if you look back at our 3Q spending of just over $31 million for SG&A combined, that will grow as A&P, advertising and promotion costs increase when we do get approvals and do launch these drugs. But I don't think you can expect that not to be. It'll be incremental growth, not a sharp curve up because, like Steve said, the field force, market access, medical affairs, etc., is fully built out.
Chris Shibutani (Analyst)
That's helpful context. Thank you.
Michael Metzger (CEO)
Thank you, Chris.
Operator (participant)
The next question is from the line of Kelly Shi with Jefferies. Your line is now open.
Kelly Shi (Analyst)
Congrats on the great progress in the quarter and for the upcoming, also very eventful Q4. First, curious your view on the clinical bar for CR/CRh rate for the pivotal NPM1 data. And also, how do we think about the correlation with OS benefit? And what is the OS benefit? What is the OS benefit expectation relative to KMT2A subgroup? Thank you.
Michael Metzger (CEO)
Great. Well, thank you, Kelly. I appreciate your kind comments. So in terms of the clinical bar for NPM1, I think we've been very consistent in our approach here. I think the data for KMT2A and NPM1 so far across all different trials, monotherapy combination has looked very consistent. And we are, based on precedent, you can look at 20%-30% CR/CRh rate as the approvable bar, as low as probably 20% could be approvable. But I think in terms of what we would expect, we've shown data in that range for NPM1, even higher at our phase I data was at 36%. So we feel very confident that the results will fall in that range and be very, very positive. So I think this is. There's an approval question, and then there's ultimately where the data falls.
And I think we feel very confident that we're going to have a result that is not only consistent with what we've seen before, but hits the mark for physicians. Obviously, the higher, the better. And then in terms of your second question on OS benefit, maybe I'll ask Anjali to make a comment.
Anjali Ganguly (Chief Strategy Officer)
Yeah, sure. So Kelly, I think in the historic data analyses that have been published, we've seen with KMT2A, with increasing lines of therapy, you have shorter and shorter survival expectations getting down to between two and three months by the time you're treating a third-line patient. It's similar for NPM1, but maybe the decrease isn't as steep. They start off as a more favorable prognosis, but over time, they will also, when they relapse, get down to shorter survival benefit. And I think in third line, it's something like four to five months benefit expectation.
Kelly Shi (Analyst)
Thank you.
Michael Metzger (CEO)
Thank you, Kelly.
Operator (participant)
The next question is from the line of Phil Nadeau with TD Cowen. Your line is now open.
Phil Nadeau (Analyst)
Good afternoon. Thanks for taking our questions. Two questions from us. So first, the updated KMT2A AUGMENT-101 data that we saw in the abstracts today, is that the most recent analysis that the FDA has? Is that what was submitted to the FDA? And is that what the FDA is reviewing? That's first. And then second, we noticed on your slides describing the pivotal trial in combination with VenAza in the frontline, there was no revumenib dose listed. Have you determined with the FDA's input what that dose is likely to be? Thanks.
Michael Metzger (CEO)
Yeah, Phil, thank you. So in terms of the KMT2A update, look, I think we tend to not comment specifically around the FDA review. And as I had said before, we described the fact that the agency had asked for additional information related to the clinical trial. And they had asked for it sort of late in the cycle review, which led to the PDUFA delay of three months where now it sits at December 26th. We have not, I'm not going to confirm or deny that this was the information that they were specifically looking for. All I can say is this information is highly consistent and supportive of approval. We had made the comment that the information that was submitted was also highly supportive of approval. And so it gives us, and I'm sure others, a lot of confidence.
I mean, you're taking the dataset from 57 patients and basically doubling it and getting ultimately the same results. I'll note that in the 57 patients that were followed for additional seven months, you had an extension of to 13 months on the duration, the median duration of response. So some encouraging signs, of course. But this is very robust data that I know investors and others were interested in seeing. And so we are keen to provide an update there. But the agency has access to all of our information. And so again, not confirming or denying, but feeling quite confident that the information here is very supportive. And then in terms of the pivotal trial, maybe I'll turn it over to Neil. We can make a comment on it. Yeah, go ahead, Neil.
Neil Gallagher (President and Head of R&D)
Yeah, sure. So Phil, thanks for the questions.
I mentioned a little earlier that the health authority approvals are currently in process. In fact, several of the submissions have been made in several countries, and we're initiating the study of 160 milligrams.
Phil Nadeau (Analyst)
That's very helpful. Thank you.
Neil Gallagher (President and Head of R&D)
You're welcome.
Michael Metzger (CEO)
Thank you.
Operator (participant)
The next question is from Michael Schmidt with Guggenheim. Your line is now open.
Michael Schmidt (Senior Biotech Analyst)
Hey, guys. Thanks for taking our questions. Two from us. Just on the KMT2A data, on the 13-month duration of response that you disclosed today in the abstract in AUGMENT-101, would you expect a similar duration in NPM1 treated patients once you have longer follow-up from that cohort? And then as we think about the menin inhibitor competitive landscape, there's been greater focus recently on differences in drug product characteristics as investors are looking to project how combinable the different agents are, particularly on PK or drug exposure metabolism. And as we continue to look at the emerging combo data at ASH, are there any learnings you can highlight where you feel confident about potential advantages for revumenib over others in the field? Thanks so much.
Michael Metzger (CEO)
Okay. So thank you, Michael. Appreciate it. So in terms of duration of response, we did note the 13-month extension on the follow-up there. I think that is an interesting result, an important result. I think the follow-up has the capacity to sometimes extend duration, especially when the upper bound hasn't been reached and you are taking a certain cut in time. So can't really comment too much on the NPM1 data and what that's going to look like at this stage. Obviously, we don't know the data. So I think we'll have to see just what that looks like at the time. But yeah, certainly encouraging around the KMT2A and patients who got transplant. I'll say, it tends to help extend time on therapy and ultimately could impact the duration.
So there may be some differences there between KMT2A, the number of patients who have KMT2A and go to transplant versus patients who have NPM1. So we'll see what that looks like. I can't really speculate at this point. And then your second question about some of the combination data and the differences between the molecules and obviously the ASH abstracts came out today. Perhaps we can draw some conclusions. I think it's a little bit early. You'll have to see some of the follow-up at ASH, right, in terms of the overall presentations. I think what we can say about our own data, specifically the SAVE data, is that it's highly encouraging of what we're seeing. These are essentially fourth-line patients who have had lots of stem cell transplant and prior venetoclax and to see extremely high rate of overall response, but even in CR/CRh, 58%.
We're seeing very good tolerability, very good duration so far. Patients are being followed for more than six months and staying on drug, the vast majority. So this is a very well-tolerated, efficacious regimen. Now in 26 patients, whereas you saw the last data cut or the last update, or first update, I should say, was at ASH last year. So highly encouraging, again, very heavily pretreated patients. We hope to have an update at our investor event on the BEAT-AML trial at ASH. And that will be an extended dataset, as Neil pointed out earlier. But we've seen excellent safety, tolerability, and efficacy adding to the doublet in the frontline patients as well. So I think our profile is really, really showing itself to be distinguished among what others are seeing in their trials.
Again, we're furthest advanced both in relapse refractory as well as in frontline setting, specifically around the VenAza and combos.
Michael Schmidt (Senior Biotech Analyst)
Thanks. Really appreciate it.
Michael Metzger (CEO)
Thank you, Michael.
Operator (participant)
The next question comes from Yigal Nochomovitz with Citi. Your line is now open.
Hi, guys. This is Ashiq for Yigal. Thanks for taking my questions and congrats on all the updates here. I just wanted to ask a follow-up on the maintenance setting questions asked earlier for revumenib. I guess for the AUGMENT-101 KMT2A cohort, there's nine out of 21 patients that got maintenance therapy, but three out of 12 in SAVE. I'm just curious if there were differences in the way those studies were run or maybe awareness among physicians that are differences regarding awareness between physicians in terms of whether or not they could use revumenib in a maintenance setting. And I'm also just curious to what degree are you aware of how physicians are sort of deciding when to use revumenib in a maintenance setting and what sort of decision matrices there are in place today? Thanks.
Michael Metzger (CEO)
Yeah, thanks, Yigal. I think this is a work in progress. As I said before, I think maintenance is a very interesting concept. We're talking about relapse refractory patients who have had a lot of prior treatment, stem cell transplants, often more than one, venetoclax as well. So there's some fragility to their treatment. And so, I think the physicians are thinking about this, and it's sort of on a case-by-case basis. There's nothing in the protocol in these two protocols that prevent them from getting maintenance. It's just up to the physician as to whether they initiate maintenance and how long they keep them on maintenance. So, as I said earlier, I think over time this will play out. And physicians, as they gain experience, they'll learn how best to administer it, how long they'll keep patients on.
And as you've seen, it's very encouraging to see sometimes up to half the patients or more getting maintenance. And it will differ from these early trials. But ultimately, we're in very good shape. Neil, you want to make a comment?
Neil Gallagher (President and Head of R&D)
Yeah, just one thing to add is that just to remind everyone that we've seen patients staying on for very extended periods of time. So we've seen patients staying on for three years or more. And physicians know that as well. I'm not going to reiterate what Michael said. It's a complex paradigm or complex thinking that goes into a decision to transplant a patient. But physicians are aware that the drug is well tolerated as a monotherapy in the post-transplant maintenance setting for prolonged periods of time. And we've heard many of them speak publicly about their willingness to actually use this as a treatment paradigm, recognizing the tolerability of the drug in that setting.
Got it. Can I just ask one more?
Michael Metzger (CEO)
Sure. Go ahead.
One more. Yeah, sorry. One more quick clarifying question. On the frontline, revumenib plus VenAza study, looks like the primary endpoint is overall survival in just the NPM1 population. But it looks like you're enrolling both NPM1 and KMT2A. So I'm wondering why just the focus on NPM1. Is that related to more population dynamics or something else? Thanks.
Yeah, I'll take that one, so thanks for the question. So yes, that is correct. The study, I think I mentioned as well in the script, the study is actually powered for the NPM1 population. As I think I also mentioned in the script, this population, so think about the population that will go into the study. These are older patients who are not suitable for intensive chemotherapy. And therefore, the predominant mutation in that population is actually NPM1. If you look, for instance, and we expect the median age of that population to be somewhere 65 or older, maybe around 65, right? So, if you look at the median age in our KMT2A population, for instance, from AUGMENT-101, the median age is 35 in the updated analysis that we just talked about, the abstract of which was published today. So KMT2A is more prevalent in the younger population.
NPM1 is more prevalent overall and more prevalent than KMT2A in the older population. In fact, KMT2A is quite rare in the older population. But we will include some of those patients as well. That's why it's designed the way it is. Does that make sense?
Yep. Makes a lot of sense. Thanks very much and congrats again.
Thanks, Ashiq.
Neil Gallagher (President and Head of R&D)
Thanks, Ashiq.
Operator (participant)
The next question is from Jason Zemansky with Bank of America. Your line is now open.
Jason Zemansky (Analyst)
Great. Thank you. Good evening. Congrats on the quarter, and thanks for taking our question, as well as the additional color on ASH. Maybe two quick ones from me. For NPM1, curious as to what you're thinking about the potential for Breakthrough Therapy designation. Have you requested this? Has FDA given you any indication, particularly given they awarded it in KMT2A? And then maybe just to circle briefly back on your previous answer regarding the NPM1 efficacy range. Certainly, you mentioned for physicians, higher the better. But is that 20% floor you mentioned necessary for approval, does that still apply or is that higher? Thanks.
Michael Metzger (CEO)
Yeah, Jason, thanks for the question. So first of all, for NPM1 in terms of breakthrough therapy designation, yeah, in the phase I, we had 14 patients that were at the RP2D, which I think we have been very clear is basically falls short of what's required for submission for breakthrough. So we didn't have the applicable data for that designation. So we had not applied at the time. And so we are right now running a trial. If we decide, obviously, once the data is available, that it's a good idea to apply for breakthrough at that point, if it helps us in our submission, then we could always apply for it. It's very important to have for your first indication, which we, of course, had, which led to our approval and other things that advantaged us with KMT2A, having breakthrough for your second indication is less impactful.
So again, just to be clear, we didn't apply for it. We didn't have the data from the phase one at the right dose. In order to substantiate that, you need at least 20 patients' worth of data. So that's how that came about. So no, we did not apply for it. And then your second question, I know you're focused on the 20% hurdle for NPM1. I think, as I said before, the precedent here, again, these therapies in AML, 20% or higher, CR/CRh rate, duration of response in the four to six month range, those are general parameters that we see other drugs get approved by. And that's just historical precedent. I think from our standpoint, having a CR/CRh rate north of 20% would be a good result because it'd likely result in a statistically significant trial. And that would be seen as approvable and impactful for patients.
I think when I said the higher, the better, it would be obviously nice to see a point estimate that's higher than that, but not necessarily mandatory. So I think we're feeling quite good. We've seen data in phase one, as I pointed out, highest in category, 36%, the RP2D. So we have no reason to believe that we're going to fall short. We feel very confident. And we've talked about the fact that there's differences between KMT2A and NPM1 in terms of transplant rate and how that potentially impacts the CR/CRh rate, which could be favorable in this regard relative to what we've seen for KMT2A. So we feel very good. And we'll see the data soon. So thank you.
Jason Zemansky (Analyst)
Great. Thanks.
Operator (participant)
The next question is from George Farmer with Scotiabank. Your line is now open.
George Farmer (Analyst)
Hi, good afternoon. Thanks for taking my questions. I really appreciate your decision to disclose the additional KMT2A data. Question on this 6.4-month duration that you showed in 97 patients with the February cutoff. Are you going to be showing anything more mature than that? And is it possible that we could see something closer to the 13 months that you reported from the first 57 patients?
Michael Metzger (CEO)
Yeah, thanks, George. I wouldn't anticipate we're going to update the dataset again. I think we have an approval coming, and we have NPM1 data to focus on. It obviously takes a lot of work to continue to interrogate a dataset. And I think we're very keen to kind of get this drug approved. And obviously, real world, we'll get a chance to see how it performs relative to all of these measures, whether it's patients staying on drug, maintenance, what have you. And so I think the 6.4 seems very consistent, obviously. The 13-month extension on the 57 was an encouraging result. I think, as I mentioned before, kind of lets us believe or potentially believe that there's a longer duration possible with follow-up. And it was a point in time. So at this point, we don't have any plans to update the dataset beyond what we've already provided.
George Farmer (Analyst)
Okay. And then the HOVON trial, when do you anticipate that concluding and to be reporting on data? Maybe I missed that in your primary comments.
Michael Metzger (CEO)
Yeah, I think we haven't given any specific timeline to conclude that. I think there's some general parameters of trials that are similar, like VIALE-A that was roughly a four-year trial or something in that range, and this is an OS-driven endpoint, so it'll take time to read out, but at the end of the day, we haven't provided a specific timeline to complete the trial just yet. We need to get it started. We'll get it started at the end of the year, and then we'll give more guidance as we go.
George Farmer (Analyst)
Okay. And then one more, if you don't mind. With the Royalty Pharma deal, were they looking at the potential of Niktimvo in IPF by any chance when they were contemplating the term?
Michael Metzger (CEO)
Yeah. So we were very excited about Royalty Pharma's partnership with us and how they really looked at the opportunity for the drug over many years, not just in GVHD, but potentially beyond that. I'll note that there is a cap on the transaction. In other words, we're paying them back 2.35 times what they've put into the transaction, which supports, and the drug forecast will support that. And then some, we believe that they looked at all of the indications and the potential indications, both in GVHD, relapse refractory, as well as the extensions, IPF included, to arrive at a forecast that supported the deal on their end. And it aligned very closely with what we believe, right? And really quite a robust forecast, which is different, of course, than what the market has believed up to this point. So we feel that the partnership is well aligned.
And the value that we were able to attain in this deal for Syndax is quite helpful and supportive long-term of our objectives.
George Farmer (Analyst)
Okay. Good. Thanks very much.
Michael Metzger (CEO)
Thank you.
Operator (participant)
The next question is from Kalpit Patel with B. Riley Securities. Your line is now open.
Kalpit Patel (Analyst)
Yeah. Hey, good afternoon, and thanks for taking the question. Just one more follow-up on that overall survival endpoint in the frontline trial. I guess I understand the rationale for just including NPM1 patients in that analysis, but is there a minimum efficacy threshold that you need for the KMT2Ar patients to make sure that they will be included on the label? Or do you just need to hit the primary endpoint for NPM1 patients?
Michael Metzger (CEO)
Yeah. Thanks for the question. So as I mentioned, the study is designed to test the hypothesis in NPM1 patients, right? So the statistical power is designed around that number. The approximate number of patients that has been disclosed publicly includes a certain amount of KMT2A patients. We will be looking for consistency of effect in the KMT2A patients, but the study is not designed to test a statistical hypothesis in those patients. Can I comment on what may happen from a regulatory perspective down the road? But the primary objective or the primary reason for conducting the study is to have the drug approved in combination with VenAza for NPM1 patients.
Kalpit Patel (Analyst)
Okay. Got it. And then at ASH, I guess what sort of additional analysis should we expect for the KMT2A patients from the pivotal cohort, if anything at all? I think a lot of investors have been wondering what the efficacy analysis is like for patients based on the number of priors and the types of priors and just looking at the baseline demographics. Thank you.
Michael Metzger (CEO)
Yeah. Go ahead, Neil. Why don't you?
Neil Gallagher (President and Head of R&D)
Yeah. Look, we've been pretty busy. We were focused on getting the abstract in as it stands. You can expect to see additional analyses, additional data presented at ASH, but we haven't been specific about exactly what those details are. But you can expect to see more detail around it at the ASH presentation. Sorry, I can't be more specific.
Kalpit Patel (Analyst)
Okay. Got it. Thank you very much.
Michael Metzger (CEO)
Thank you.
Operator (participant)
The next question comes from Justin Zelin with BTIG. Your line is now open.
Justin Zelin (Analyst)
Thanks for taking our question and congrats on the progress. So on the revumenib filing, I understand that patients are regularly tested for KMT2A status, but do you expect you'll need a companion diagnostic for approval?
Michael Metzger (CEO)
Yeah. Thanks, Justin, for the question. No, I don't. I think, look, we haven't really gotten into discussion about what will be necessary for regulatory approval. But there is precedent for companion diagnostic post-approval. So I think at this point, we feel very confident that we'll be able to get the drug approved and that there may be a requirement down the line for a companion diagnostic. But for KMT2A, there are some existing diagnostics available that make testing available and robust. So at this stage, a little bit more to say post-approval, but I think at this point, we have all the confidence that we're on track to get the drug approved, and we'll follow up for that.
Justin Zelin (Analyst)
Great. Great. Thanks for taking our question.
Michael Metzger (CEO)
Thank you.
Operator (participant)
This concludes our question-and-answer session. I'll now turn the floor over to Mr. Michael Metzger for any additional comments or closing remarks.
Michael Metzger (CEO)
Thank you, Operator, and thank you all. We appreciate you tuning in today to discuss our recent progress and the transformative milestones that we have ahead. We look forward to seeing many of you at the upcoming Guggenheim, UBS, Stifel, and Jefferies conferences in November, as well as our ASH event in December. And with that, have a great evening.