Syndax Pharmaceuticals Inc

NASDAQ:SNDX

Earnings Call Analysis

Syndax Pharmaceuticals Progresses with Key Drug Approvals and Financial Health

In Q3 2024, Syndax Pharmaceuticals celebrated significant milestones, including FDA approval for Niktimvo, the first approved treatment for chronic GVHD. The company secured a $350 million royalty agreement for Niktimvo, enhancing its financial stability as it approaches profitability. Anticipated FDA approval for Revumenib is expected by December 26, 2024, addressing an urgent need in KMT2A acute leukemia, with a potential market near $2 billion. The forecasted total expenses for 2024 are narrowed to $365-$370 million, with R&D expenses expected at $245-$250 million. Syndax aims for aggressive market penetration with both therapies, leveraging prior clinical successes.

Syndax's Growth and Strategic Enhancements

In the third quarter of 2024, Syndax Pharmaceuticals showcased significant growth, marking its transition from a development organization to an integrated commercial stage company. This transformation is exemplified by a notable $350 million royalty agreement for their newly FDA-approved drug, Niktimvo, indicating an underappreciated market potential for this treatment. The financial influx bolsters Syndax's ability to not only fund the rollout of Niktimvo and Revumenib but also to invest in ongoing development across its pipeline.

Niktimvo Approval and Market Opportunities

Syndax achieved FDA approval for Niktimvo, the first CSF1R antibody for treating chronic graft versus host disease (chronic GVHD), after at least two previous systemic therapies. Moreover, the positive results from the pivotal AGAVE-201 trial, published in the New England Journal of Medicine, and Niktimvo's inclusion in the NCCN guidelines enhance its market credibility. Syndax estimates an addressable market of $1.5 billion to $2 billion for third-line chronic GVHD treatments in the U.S.

Revumenib’s Coming Launch and Market Impact

The anticipated launch of Revumenib, aimed at treating relapsed or refractory KMT2A-rearranged acute leukemia, is on track for FDA approval by December 26, 2024. The combined addressable patient population for KMT2A and NPM1 categories is estimated between 5,000 to 6,500 patients, with an overall market potential nearing $2 billion. Revumenib's well-supported clinical data highlights its potential to be the first-in-class therapy for acute leukemia, which is crucial given the urgent need in this high-risk patient population.

Financial Guidance and Cost Management

Syndax's operational expenses reached $102.1 million in Q3 2024, with expectations set for total expenses between $365 million to $370 million for the year. Research and development costs are forecasted to be between $245 million and $250 million. Notably, they anticipate lower noncash stock compensation expenses, further optimizing financial management.

Investor Confidence and Future Trajectory

The partnership with Royalty Pharma aims at maximizing Niktimvo's value, with structured royalty agreements to enhance long-term financial prospects. As Syndax prepares for the upcoming launches, investor confidence remains high based on their proactive market strategies, commercial capabilities, and upcoming product approvals. The committed team and thorough preparation ensure they are well positioned to capture market share and meet urgent patient needs in oncology therapeutics.

Earnings Call Transcript 2024-Q3

[Operator]

Good day, everyone, and welcome to the Syndax Third Quarter 2024 Earnings Conference Call. Today's call is being recorded. [Operator Instructions]

At this time, I'd like to turn over the call to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.

[Sharon Klahre, executive]

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 Klahre, 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 Ganguli, Chief Strategy Officer. This call is accompanied by a slide deck that has been posted on the Investors page of the company's website. You can now turn to our forward-looking statements on Slide 2.

Before we begin, I'd like to remind you that any statements made during 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 Factors section in the company's most recent quarterly report on Form 10-Q as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, November 5, 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, executive]

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 data set and the important role of Niktimvo in the treatment [ pharmamentarium ]. 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 relapse 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, [indiscernible] 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 acute rearrange acute leukemia from the Phase II portion of our AUGMENT-101 trial and new combination data for 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 9. 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, executive]

Thanks, Michael. It's a pleasure to be with you all today to discuss the latest data emerging from a robust clinical development program, investigating Revumenib across the treatment continuing 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 are 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.

Turning to Slide 4. At ASH, we will be presenting an updated analysis that includes additional patients enrolled in the pivotal Phase II portion of the AUGMENT-101 trial of Revumenib patients with relapsed or refractory KMT2A rearranged acute leukemia. These new data are highly consistent with what was previously reported with the recent reported data or [ other ] that fall on 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 2, with 44% of the population having received 3 or more prior treatments, 63% had prior exposure to 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 9 patients resumed Revumenib as maintenance therapy following transplant. The median duration of CR/CRh rate 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 [ CR/C ] 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 at 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 5. 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 of 7 additional months of follow-up, the updated median duration has extended to 13 months. At the time of the most recent data cutoff, 5 of the 13 patients remained in [indiscernible] without relapse.

Moving to Slide 6. SAVE is an investigator-sponsored 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 [indiscernible] 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% of [ mutant ] NPM1 and 20% of NUP98 rearrangements. Patients had received a median of three prior lines of therapy, including 65% to receive prior Venetoclax and 42% who had prior stem cell transplants. The combination was well tolerated with this 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 [ oil ] oral combination showed promising results is of note that 2/3 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 are 46% preceded to stem cell transplant with 3 patients resuming [ Revumenib ] following transplant. With a median follow-up of 6.4 months, the 6-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 combined ability of Revumenib, Venetoclax and [ hypomethylating ] agents are encouraging. We look forward to sharing further data from this trial in due course, including from a frontline cohort that is now enrolling.

Turning to Slide 7. The two trials that I just reviewed are important parts of our comprehensive clinical development program, evaluating Revumenib [ cost ] to 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 who are enrolled in remission and their MRD status is monitored. Patients who become MRD positive or experienced early relapse are then allocated to treatment. As of the data cutoff, 9 patients with MRD relapse, including 8 with mutant NPM1, and one with KMT2A rearranged AML were enrolled in the safety court and received Revumenib, three patients had prior Venetoclax exposure and 6 had prior intensive chemotherapy. The preliminary data for [ NPM1 ] patients treated with Revumenib are promising with 5 of 8 patients achieving a reduction in measurable at residual disease, including 3 who achieved MRD negativity within 6 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 & Lymphoma Society. This trial is evaluating in the combination of Revumenib with Venetoclax, [indiscernible] in frontline patients with NPM1 or KMT2A AML. Data from the trial were recently presented at the European Hematology Association meeting in June, the CRC 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 8, 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 [indiscernible], a newly diagnosed adults with mutant NPM1 or KMT2A AML who were considered ineligible for intensive chemotherapy. This will be 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. And 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 ven/aza or Revumenib plus ven/aza. The primary endpoint is overall survival in patients with mutant NPM1 AML. Secondary endpoints include event-free survival, rate of CR/CRh rates of response without MRD. We expect the first site to be open for enrollment by year-end.

Turning to Slide 9. Ahead of our top line readout from the Phase II cohorts of patients with relapsed/refractory mutant NPM1 AML from AUGMENT-101, I wanted to briefly review the unmet need of these patients. Mutations in [ nucleophosmin one ] gene are the most common genetic alterations in AML occurring and 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 ], 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 [ KMT2-AR ] patients. Based on historical approvals of other AML therapies, we believe that a CR/CRh rate of 20% to 30% with a median duration of response in the 4- to 6-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?

[Steven Closter, executive]

Yes. 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 [indiscernible], another drug indicated [ from ] 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 billion to $2 billion estimated totable 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 Insight 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 falls 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 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 we 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 of 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 2.5 months, a truly devastating prognosis for patients. Given this is a high-risk population, centers are already routinely testing for KMT2A rearrangement. Further, with compelling data across both KMT2A and MPN1 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 and 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 do position 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 to 6,500 patients in the relapsed or refractory setting in an addressable market opportunity that approaches $2 billion in the U.S. In summary, I'm very excited and positively impacting 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, executive]

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 30 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 2024, the company is narrowing its guidance and now expects research and development expenses to be $245 million to $250 million and total expenses to be $365 million to $370 million. Note that the guidance range for operating expense for the full year 2024 includes an estimated $41 million of noncash stock compensation expense, which is down from our previously estimated $43 million and that research and development expense guidance includes any milestones earned or expected to be earned by our partners for potential approvals.

With that, let me now turn the call back over to Mike.

[Michael Metzger, executive]

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 can 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 data set, which gives us the opportunity to further solidify our position in the emerging median 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]

[Operator Instructions] The first question will come from Anupam Rama with JPMorgan.

[Priyanka Grover, analyst]

This is Priyanka on for Anupam. Just a quick question from us, post the potential approval of KMT2A and pending positive NPM1 data of Revumenib, can you remind us of the process to get into guidelines and potential time line considerations we should be thinking about?

[Michael Metzger, executive]

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'll submit for guidelines. They meet the NCCN guideline panels meet probably twice a year, but they do it and on an ad hoc basis as well. So there's the opportunity for important approvals as we would expect these to be engaged and brought into the guidelines pretty expeditiously. And we did actually experienced 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, and then we were into -- within two to three weeks, we were into the guidelines. So that is all very much the plan to move as quickly as possible to move into guidelines.

[Operator]

The next question will come from the line of Brad Canino with Stifel.

[Bradley Canino, analyst]

Two topics for me for now. For AUGMENT-101, in the updated data, you noted 9 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 [ Hovan ] collaboration for frontline AML. I think you do point to BEAT AML updates in 4Q '24. Help us understand what you're looking for in those data to finalize and initiate that pivotal trial?

[Michael Metzger, executive]

So maybe I'll take the first question, and then I'll pass it over on BEAT AML trial to Neil. So in terms of the AUGMENT-101 trial, we did note that there were certain patients that would back on maintenance. And that is a trial-driven result. Patients were allowed -- physicians were allowed to put their patients back on therapy post [ engraftment ] and many physicians elected to do so. We do expect that, that phenomenon will continue to advance once the drug is 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 going to transplant but get back on therapy and stay on therapy for an extended ended 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, executive]

So what I think everyone should expect is more patients, right? Specifically more patients treated at dose level 1. So the combination of 113 milligrams of Revumenib with Venetoclax, [ 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.

[Operator]

The next question is from the line of Peter Lawson with Barclays.

[Peter Lawson, analyst]

Just with the sale of some of the royalty stream from the Niktimvo, does that accelerate any programs under the development?

[Michael Metzger, executive]

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 lands 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's 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 million, it's about $750 million actually -- just to correct myself.

[Peter Lawson, analyst]

And then the timing of the NPM1 data, is that 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, executive]

Right. So I think the order of events here, you get approval on your molecule, we'll have obviously, pivotal data within that same time frame 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 we -- you could use -- 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.

[Operator]

The next question is from the line of Chris Shibutani with Goldman Sachs.

[Chris Shibutani, analyst]

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?

[Michael Metzger, executive]

Great. Thanks so much, Chris. So maybe I'll turn it over to Steve to talk a little bit about the, as you say, the early launch trajectory and that question related to 2025.

[Steven Closter, executive]

Yes. So good question, Chris. I think in terms of trajectory, I think, is the market ready and is the [indiscernible] and I think the answer is yes. We've seen a real and growing market. Very encouraging. If you look at latest sales for Rezurock which I mentioned by comments, it's [indiscernible] annualizing well over $500 million a year. It's in its mid-third year of promotion. Any of the market research we've done suggests that patients are some happy with treatment, but many are dissatisfied. So we know there's a need.

And 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 have essentially built this market. They're in market now and calling on all the important customers. I mentioned a little under 200 transplant centers in the country, [indiscernible] 35 of them generate half of the patient volume. They're already there profiling. So it's a small targeted group that are already there. We'll obviously add some effort and everything is in place to pull this product through at launch. There's a, we'll say, a small bolus of patients that are always looking for something new. We may see those coming to 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 [indiscernible] and pull through.

[Michael Metzger, executive]

Right. And so maybe you want to comment on Revumenib as well?

[Steven Closter, executive]

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. I think what that's enabled us to do from a preparedness standpoint, is to be ready. The market is ready. We've been able to focus on [ net and inhibition ] as a mechanism of disease. The awareness is high. We've got a very talented team that's been put in place. So they started calling the customers back into June time frame. We've got about 2,000 accounts that we call on for Revumenib. There's about 200 that cover 2/3 of the patient opportunity. we prioritize 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 6. They came in with a pre-existing relationship. So we know a lot about our accounts and how we think about AML and [ AMLL ] where the role in KMT2A will place testing is very high. We're understanding how the pull things through. And then on the payer side, we have been calling customers for well over a year. So goal is to get on to formulary as close to approval as we can, generally takes about 9 to 12 months with all the activity we have placed against payers. We think we can [indiscernible] that to a 6 to 9-month [indiscernible]. We've also got a really great group of specialty pharmacies and distributors in place that are the best at what they do. So we'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 [indiscernible] patients are too sick. I think I mentioned the prognosis for patients with relapsed/refractory KMT2A [indiscernible] is about 2.5 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.

[Keith Goldan, executive]

And 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 then do launch these drugs. But I think you could expect that not to be -- it will be incremental growth, not a sharp curve up because like Steve said, this [ field force ], market access, medical affairs, et cetera, is fully built out.

[Operator]

The next question is from the line of Kelly Shi with Jefferies.

[Dingding Shi, analyst]

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?

[Michael Meyers, executive]

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 Based on precedent, you can look at 20% to 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 there's an approval question, and then there is ultimately what -- 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.

Then in terms of your second question on [ OS ] benefit, maybe I'll ask Anjali to make a comment.

[Anjali Ganguli, executive]

Yes, 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 2 and 3 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 4 to 5 months benefit expectation.

[Operator]

The next question is from the line of Phil Nadeau with TD Cowen.

[Philip Nadeau, analyst]

Two questions from us. So first, the updated KMT2A AUGMENT-101 data that we saw in the abstract today. Is that the most recent analysis that the FDA has? Is that what was submitted to the FDA and that 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 ven/aza in the front line. There was no Revumenib dose listed. Have you determined with the FDA's input what that dose is likely to be?

[Michael Metzger, executive]

So in terms of the KMT2A update, look, I think we've -- we tend to not comment specifically around the FDA review and what -- and as I've 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 '26. We have not -- I'm not going to confirm or deny that this is the information that they were specifically looking for. All I can say is this information is highly consistent and supportive of approval. We have made the comment that the information that was submitted was also highly supportive approval. So it gives us -- and I'm sure there's a lot of confidence. I mean you're taking the data set 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 7 months, you had an extension of to 13 months on 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 and we can make a comment on it. Go ahead, Neil.

[Neil Gallagher, executive]

So Phil, thanks for the question. I mentioned earlier, the [ 30 ] approvals are currently in process. In fact, there are several of the submissions have been made in several countries, and we're initiating the study 160 milligrams.

[Operator]

The next question is from Michael Schmidt with Guggenheim.

[Michael Schmidt, analyst]

Two from us. Just on the KMT2A data on the 13 months duration of response that you disclosed today in the [ ASH abstract ] in AUGMENT-101, would you expect a similar duration in NPML1 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 product characteristics as investors are looking to project how combinable the different agents are, particularly on [ PK ] or drug explosion 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?

[Michael Metzger, executive]

So in terms of duration of response, I did note the 13-month extension on the follow-up there. I think the -- that is, I think, an interesting result and 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 I can't really comment too much on the NPLM1 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 yes, certainly encouraging around the KMT2A and Patients who got transplant, I'll say, tends to help extend time on therapy and ultimately could impact the duration. So here 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. it's -- 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 in prior Venetoclax and to see extremely high rate of overall response, but in CRC, CR/CRH, 58%, we're seeing very good tolerability, very good duration. So far, patients are being followed for more than 6 months and staying on drug, the vast majority. So this is a highly well-very well-tolerated efficacious regimen now in 26 patients, where as 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 data set, 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 relapsed/refractory as well as in frontline setting specifically around the ven/aza combos.

[Operator]

The next question comes from Yigal Nochomovitz with Citi.

[Ashiq Mubarack, analyst]

This is Ashiq on for Yigal. 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 9 out of 21 patients that got maintenance therapy, but 3 out of 12 in SAFE. I'm just curious if there were differences in the way those studies were run or maybe awareness among physicians that -- differences is among -- 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 how -- when to use Revumenib in a maintenance setting and what sort of decision matrices there are in place today?

[Michael Metzger, executive]

Yes. Thanks. I think this is a work in progress. As I said before, I think maintenance is a very interesting concept. We're talking about relapsed/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 you -- 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 it's -- 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 are more getting maintenance and it will differ from these early trials. But ultimately, we're in very good shape. [ Neil ], Do you want to make a comment?

[Neil Gallagher, executive]

Yes. Just one thing to add is that, just to remind everyone that we've seen patients staying on for very extended period two times. So we've seen patients staying on for three years or more. So we know -- 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 the decision to transplant, to patients 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.

[Ashiq Mubarack, analyst]

One more quick clarifying question on the frontline Revumenib plus ven/aza 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 to focus on NPM1 is that related to more population dynamics or something else?

[Neil Gallagher, executive]

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. I think I also mentioned in the script, this population, so think about the population that we'll 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 agent, our KMT2 population, for instance, from AUGMENT-101, the median age was 35 in the updated analysis that we just talked about, the abstract of which was published today. So KMT2A is more prevalent in the [indiscernible] population, NPM1 is more prevalent overall and more [ clever ] that KMT2 -- older population. In fact, KMT2A is quite rare in the older population [indiscernible] includes some of those patients as well. That's why it's designed the way it is. Does that make sense?

[Ashiq Mubarack, analyst]

Yes. Makes a lot of sense.

[Operator]

The next question is from Jason Zemansky with Bank of America.

[Jason Zemansky, analyst]

Maybe two quick ones from me. For NPM1, curious as what you're thinking about the potential for breakthrough therapy designation? Have you requested this as 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 efficiency range or 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?

[Michael Metzger, executive]

So first of all, for NPM1 in terms of breakthrough therapy designation, we had in the Phase I, we had 14 patients that were at the RP2D, which I think we have been very clear, it basically falls short of what's required for submission for breakthrough. So we didn't have the applicable data for that designation. So we have 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 [indiscernible] 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. It didn't -- we didn't have the data from the Phase I 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% are higher CR/CRh rate, duration of response in the 4- to 6-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 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 1, as I pointed out, it's 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 see for KMT2A. So we feel very good, and we'll see the data soon. So thank you.

[Operator]

The next question is from George Farmer with Scotiabank.

[George Farmer, analyst]

A 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, executive]

I wouldn't anticipate we're going to update the data set 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 data set. 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-month 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 I just -- at this point, we don't have any plans to update the data set beyond what we've already provided.

[George Farmer, analyst]

And then the [ Hovan ] trial, when do you anticipate that concluding and to be reporting on data? Maybe I missed that in your primary comments?

[Michael Metzger, executive]

Yes. I think we haven't given any specific time line to conclude that. I think there's some general parameters of trials that are similar like [indiscernible] that was roughly a 4-year trial or something in that range. And this is an OS driven endpoint. So it will take time to read out. But at the end of the day, we haven't provided a specific time line 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]

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, executive]

Yes. So we're 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, they have a -- we're paying them back 2.5x what they've put into the transaction, which supports and the drug forecast seemed it will support that. And then some, we believe that they looked at all of the indications and the potential indications, both in GVHD as -- relapsed/refractory frontline 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.

[Operator]

The next question is from Kalpit Patel with B. Riley Securities.

[Kalpit Patel, analyst]

Just one more follow-up on that overall survival endpoint in the frontline triplet 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 KMT2A 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?

[Neil Gallagher, executive]

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 predicting the study is to have the drug approved in combination with ven/aza for NPM1 patients.

[Kalpit Patel, analyst]

And then at ASH, I guess what sort of additional analysis should we expect for the KMT2A patients from the pivotal cohort, if any, 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 a baseline demographic.

[Neil Gallagher, executive]

Yes. Look, we've been pretty busy. We're 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 presentation. Sorry, I can't be more specific.

[Operator]

The next question comes from Justin Zelin with BTIG.

[Justin Zelin, analyst]

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 Meyers, executive]

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 companion diagnostic. But there is -- 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 [ off ] to that.

[Operator]

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, executive]

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.