Syndax Pharmaceuticals Q3 2024 Earnings Call Transcript

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Provided by Quartr
November 5, 2024

Key Takeaways

  • The $350 million royalty agreement with Royalty Pharma for Nictimbo strengthens the balance sheet and funds Syndax through profitability to support launches and pipeline expansion.
  • The FDA approved Nictimbo as the first CSF1R antibody for chronic graft-versus-host disease, published pivotal NEJM data, and gained NCCN guideline inclusion ahead of an Incyte-led Q1 2025 commercial launch.
  • Revumenib (selective menin inhibitor) has a PDUFA date of December 26, 2024, for relapsed/refractory KMT2A rearranged AML, with top-line AUGMENT-101 data in mutant NPM1 AML expected this quarter.
  • Updates previewed at ASH include expanded AUGMENT-101 data showing a consistent 64% overall response rate, median response extended to 13 months, high MRD negativity, and promising combination results from the SAVE trial.
  • At September 30, Syndax reported ~$749 million in cash and investments, narrowed its 2024 R&D guidance to $245–250 million, and trimmed total operating expense guidance to $365–370 million.
AI Generated. May Contain Errors.
Earnings Conference Call
Syndax Pharmaceuticals Q3 2024
00:00 / 00:00

There are 16 speakers on the call.

Operator

Good day, everyone, and welcome to the Syndax Third Quarter 2024 Earnings Conference Call. Today's call is being recorded. At this time, I'd like to turn over the call to Sharon Clary, Head of Investor Relations at Syndax Pharmaceuticals.

Speaker 1

Great. Thank you, operator. Welcome, and thank you all for joining us today as we review Syndax's Q3 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 Doctor. Neil Gallagher, President and Head of R and D Steve Gloucester, Chief Commercial Officer and Keith Goldin, Chief Financial Officer.

Speaker 1

Also joining us on the call today for the question and answer session are Doctor. Peter Ordentlich, Chief Scientific Officer Doctor. Angeline 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 2.

Speaker 1

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.syndex.com, following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer.

Speaker 2

Thank you, Sharon. Good afternoon, everyone, and thank you for joining us today. We made remarkable progress in the Q3. 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 $350,000,000 royalty agreement for Nictimbo with Royalty Pharma, we have strengthened our balance sheet significantly and now have the capital to fund Syndax through profitability, ensuring strong launches for revumenev and Nictimbo and solidifying our commitment to their continued development and expansion of the pipeline overall.

Speaker 2

Importantly, this deal further highlights how vastly underappreciated the value of Nictimbo is in the market and why it remains a critical element of our long term strategy. Let me now dig into some Q3 milestones. In August, we received FDA approval for nictimbo, the 1st and only CSF1R antibody approved for the treatment of chronic graft versus host disease or GvHD after failure of at least 2 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-two zero one trial results were published in the New England Journal of Medicine and NIKTIMBO was added to the latest NCCN guidelines, 2 achievements that highlight the significance of this dataset and the important role of NIKTIMBO in the treatment of armamentarium. With Incyte's deep understanding of the CGVHD market and long standing relationships with key stakeholders, we are thrilled to partner with them to bring this much needed new option to patients.

Speaker 2

Later in the call, Steve will provide more color on our plans for the commercial launch. We believe the approval of nictimbo 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 niktimbo 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 niktimbo, we've also continued to make excellent progress advancing revimenin, 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 revimeniv is poised to become 1st in class and practice changing therapy for KMT2A and MPM-one acute leukemia.

Speaker 2

In addition to the anticipated approval of revumentiv, we are also looking forward to the top line readout from the pivotal cohort of patients with mutant MPM-one AML, our AUGMENT-one hundred and one trial this quarter. In the recent months, we've executed on multiple initiatives that we believe lay the foundation for a strong revumentib 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-one hundred and one trial supporting the use of revumentib in relapsed or refractory KMT2A rearranged acute leukemia in the Journal of Clinical Oncology. This publication is raising awareness of revumentib'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 revumentib data in KMT2A acute rearranged acute leukemia from the phase 2 portion of our AUGMENT-one hundred and one trial and new combination data from the investigator sponsored SAVE trial.

Speaker 2

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, revumentib 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 revimatib clinical development program. Neil?

Speaker 3

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 revimatib across the treatment continuum in both adults and pediatric patients with KM2A rearrangements or mutant MPM1 acute leukemias. Through a thoughtful combination of Syndax sponsored and investigator sponsored trials, we're rapidly generating data supporting the use of revumeneb 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

Speaker 4

number of ongoing

Speaker 3

trials and briefly review the revumentum 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 2 portion of the AUGMENT-one hundred and one trial of revimativ in patients with relapsed or refractory KMT2A rearranged acute leukemia. These new data are highly consistent with what was previously reported with the recently 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.

Speaker 3

And the efficacy population has expanded to a total of 97, 40 more than in the original analysis. The median age is 35.24 percent 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 CRCRH rate of 23% and a composite complete response rate of rate of 23% and a composite complete remission rate of 42%.

Speaker 3

21 of the 62 responders or 34% went on to receive allogeneic stem cell transplant and 9 patients resumed rivulinumab as maintenance therapy following transplant. The median duration of CRCRH was 6.4 months at the time of the data cuff. Among patients who are evaluable, 61% of CRCRH 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 revumab are indicative of its best in class potential.

Speaker 3

Revumeneb 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 CRC or HRH 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 7 additional months of follow-up, the updated median duration has extended to 13 months.

Speaker 3

At the time of the most recent data cutoff, 5 of the 13 patients remained in follow-up without relapse. Moving to Slide 6. SAVE is an investigator sponsored Phase Ib trial conducted by Doctor. Issa at the MD Anderson Cancer Center. The trial is evaluating an all oral combination of revumenab, venetoclax and oral decitidine in children and adults with relapsed or refractory AML or mixed lineage acute leukemias.

Speaker 3

As you may recall, at last year's ASH meeting, Doctor. Ise presented promising data from the first 9 patients enrolled in the trial. This new abstract includes data from 26 patients with a median age of 35. 42% of the patients had KM2A rearrangements, 38% of mutant NPM1 and 20% had UP-ninety eight rearrangements. Patients had received a median of 3 prior lines of therapy including 65% who received prior venetoclax and 42% who had prior stem cell transplant.

Speaker 3

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 oral combination showed promising results. As of note, that 2 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 12%. Among the MRD evaluable patients with CR CRH, 13 of 14 patients or 93% were MRD negative.

Speaker 3

12 patients or 46% proceeded to stem cell transplant with 3 patients resuming that revument of 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 CRC or HRH was not reached. As of the data cutoff, 2 patients have completed maintenance post stem cell transplant and remain in remission. These data, which further support the combinability of revimenop with venetoclax and hypomethylating agents are encouraging.

Speaker 3

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 revivumed 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 revumenev to target measurable residual disease or early relapse in patients with AML.

Speaker 3

Patients who 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, 9 patients with MRD relapse including 8 with mutant MPM1, 1 with KM2a rearranged AML were enrolled in the safety court and received revimenop. 3 patients had prior venetoclax exposure and 6 had prior intensive chemotherapy. The preliminary data from mutant MGMTM-one patients treated with revumanibil promising with 5 of 8 patients achieving a reduction in measurable residual disease, including 3 who achieved MRD negativity within 6 cycles.

Speaker 3

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 revimenop with venetoclaxinacitin in frontline patients with NPM1 or KMT2 AR AML. Data from the trial were recently presented from the European at the European Hematology Association meeting in June. The CRC rate was 96%.

Speaker 3

We are looking forward to the next anticipated update in the Q4 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 revumetab in combination with venetoclax and azacitidine or venasa in newly diagnosed adults with mutant MPM-one or K-two-two AML who are considered ineligible for intensive chemotherapy.

Speaker 3

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.

Speaker 3

And as I mentioned, we're very pleased to be partnering with the group. The trial will enroll approximately 400 patients, randomized one to 1 to receive placebo plus venaza or revimenop plus venaza. The primary endpoint is overall survival in patients with mutant MPM-one AML. Secondary endpoints include event free survival rate of CR, CRH and rates of response without MRD. We expect the first site to be open for enrollment by year end.

Speaker 3

Turning to Slide 9. Ahead of our top line readout from the Phase II cohorts of patients with relapsedrefractory mutant MP1 AML from AUGMENT-one hundred and one, I wanted to briefly review the unmet need of these patients. Mutations in nucleophosphine 1 gene are the most common genetic alterations in AML occurring in approximately 30% of adults with the disease. While MTM-one 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 6 months or less after 3 or more lines of therapy. As compared to patients with other genetic alteration such as K2A rearrangements, patients with MPM-one AML tend to be older and less fit to, for instance, receive intensive chemotherapy and proceed to transplant.

Speaker 3

In the Phase I trial of revumeneb in patients with relapsedrefractory mutant MPM1 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 K22AR patients. Based on historical approvals of other AML therapies, we believe that a CRCRA rate of 20% to 30% with a median duration of response in 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 MTM-one cohort in OGMENT-one hundred and one 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.

Speaker 3

Steve?

Speaker 5

Yes. Thank you, Neil. Starting with Slide 10, we are thrilled that Nictimvo is now FDA approved and included in the latest NCCN guidelines as a recommended treatment for chronic GVHD after failure of at least 2 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 Q1 of 2025. Addressing the needs of patients who have progressed after at least 2 prior lines of therapy is an attractive commercial opportunity.

Speaker 5

For example, in the 3 years since launch of belumosidol or Rezaroc, another drug indicated for the same line of treatment as Nyctinvo, net sales continue to grow in the high double digits and suggest that the drug is now annualizing at over $500,000,000 in U. S. Sales alone. With the new mechanism and clinical data showing that nictimvo 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 $1,500,000,000 to $2,000,000,000 estimated total addressable market for third line or later chronic GVHD treatment in the U. S.

Speaker 5

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 Nictimvo 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 fall squarely within the larger group of accounts that are also important for revumentib, creating opportunities for commercial synergy. In addition to preparing for the launch of Nictemvo, we and Incyte are also continuing to advance clinical trials evaluating Nictemvo in earlier lines of chronic GvHD treatment and other diseases.

Speaker 5

Incyte is now enrolling patients in a Phase 2 trial of nictimvo in combination with Jakafi in patients with newly diagnosed chronic GvHD and we continue to enroll patients in a Phase 2 trial on top of standard of care in IPF and top line data expected from that trial in 2026. Turning to Slide 11, revumetab 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 1st mover advantage. We have built a highly experienced commercial organization that is already engaging with key stakeholders and is ready to launch revumetim as soon as we receive the anticipated FDA approval before the end of the year in relapsed or refractory KMT2A rearranged acute leukemia.

Speaker 5

We believe that physicians' familiarity with RevuMETA 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 2 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 rearrangements. Further, with compelling data across both KMT2A and MPM-one alterations as well as adult 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.

Speaker 5

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 2 distinct market segments in acute leukemias, KNT2A and MPM1, 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 $2,000,000,000 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 niptimbo and revumetim.

Speaker 5

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. Thanks, Steve. Turning to Slide 12, we expect that the $399,600,000

Speaker 6

in cash equivalents and short and long term investments in our balance sheet as of September 30, plus the $350,000,000 in cash received from the royalty funding agreement for Hank Timbo, provides sufficient cash for Syndax to reach profitability. Under the terms of the royalty funding agreement, Syndax received $350,000,000 in exchange for a 13.8% royalty on U. S. Net sales of Mictimbo. Royalty payments to Royalty Pharma are capped, which preserves the upside longer term for opportunities, including treatment of frontline chronic GVHD and IPF.

Speaker 6

Our financial strength allows us to fund the commercialization of nyctymbo as well as the anticipated launch of revumentib, while also appropriately investing in our pipeline to fuel continued growth and value creation. Turning to the income statement. Operating expenses in the Q3 were $102,100,000 and included $71,000,000 of research and development expense and $31,100,000 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 $245,000,000 to $250,000,000 and total expenses to be 3.65 to $370,000,000 Note that the guidance range for operating expense for the full year 2024 includes an estimated $41,000,000 of non cash stock compensation expense, which is down from a previously estimated $43,000,000 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.

Speaker 2

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 revimetinib 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 revimeneb and we are extremely focused on leveraging our 1st mover advantage to build long term franchise value. This quarter will be we will be presenting the 1st pivotal NPM1 dataset, which gives us the opportunity to further solidify our position in the emerging menin space.

Speaker 2

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

The first question will come from Anupam Rama with JPMorgan. Your line is now open.

Speaker 4

Hi, guys. This is Priyanka on for Anupam. Just a quick question from us. Post the potential approval of KMT 2A and pending positive NPM 1 data for revimeneb, can you remind us of the process to get into guidelines and potential timeline considerations we should be thinking about?

Speaker 2

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.

Speaker 2

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, to be engaged and brought into the guidelines pretty expeditiously. And we did actually experience that with axotilumab. 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.

Speaker 2

And then we were into within 2 to 3 weeks, we were into the guidelines. So that is all very, very much the plan to move as quickly as possible to move into guidelines.

Speaker 4

Thank you so much for answering my question.

Speaker 2

Thank you.

Operator

The next question will come from the line of Brad Camino with Stifel. Your line is now open.

Speaker 7

Thank you. Lots to talk about and I look forward to asking more at ASH, but two topics for me for now. For AUGMENT-one hundred and one, in the updated data, you noted 9 of 21% or 42% of transplanted patients restarted revimator maintenance. Is that a maintenance percentage rate you expect in the commercial setting? Or could it be higher?

Speaker 7

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 4Q 'twenty four. Help us understand what you're looking for in those data to finalize and initiate that pivotal trial? Thank you.

Speaker 2

Yes. Thank you, Brad. So maybe I'll take the first question and then I'll pass it over on the beta AML trial to Neil. So in terms of the AUGMENT-one hundred and one trial, we did note that there were certain patients that went back on maintenance. And that is a trial driven result.

Speaker 2

Patients were allowed, physicians were allowed to put their patients back on therapy post engraftment and many, 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 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-one hundred and one in that regard. And then beta AML, I think I'll turn it over to Neil in terms of what we expect on an update.

Speaker 3

Sure. Thanks, Brad. 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 reviumenib with venetoclaxinacicitin and some more patients also compared to what was previously reported.

Speaker 3

One thing, just a point of clarification, that is not rate limiting for us. We're currently actually applying for a 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. Your line is now open.

Speaker 8

Okay. Thanks so much. Just with the sale of some of the royalty streams from the Kimbo, Does that accelerate any programs under development?

Speaker 2

So Peter, I think the setup with the royalty agreement, which was extremely positive for us, does, of course, bring in $350,000,000 of cash onto the balance sheet. And pro form a lands us at somewhere around $800,000,000 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, you know, definitely helps us aggressively move forward with plans for revimeneb and for axitilumab, nyctimbo. So it really advances the portfolio overall and gives us the opportunity to expand the portfolio with other molecules as well.

Speaker 2

So it's very, very happy, very healthy balance sheet. Per form a, I think I said, approaching $800,000,000 it's about $750,000,000 actually, just to correct myself. Thank you, Brett. Thank you, Peter. And

Speaker 8

then the timing of the MPM-one data, is that or after a publication? How we should be thinking about that? And kind of if it's direct to NCCN guidelines or you kind of thinking supplemental?

Speaker 2

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 the 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.

Speaker 2

But for MPM 1, you publish that data and then you submit it to guidelines. It moves independently of approval. So you could use, you know, 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 MPM-one.

Speaker 8

Got you. Okay, perfect. Thanks so much.

Speaker 2

Thank you.

Operator

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

Speaker 9

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 NIKTIMBO?

Speaker 9

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 and A start aspect? Thank you.

Speaker 2

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.

Speaker 5

Yes. So, good question, Chris. I think in terms of trajectory, I think is the market ready and is there unmet need? I think the answer is yes. We've seen a real growing market, very encouraging.

Speaker 5

As you look at the latest sales for Resverag, which I mentioned in my comments, it's Entravnitz annualizing well over $500,000,000 a year. It's in its 3rd 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.

Speaker 5

So we've had a little extra time to get prepared. We're lucky that we're partnered with Insight. They've essentially built this market. They're in market now, calling on all the important customers. I mentioned there's over a little under 200 transplant centers in the country.

Speaker 5

We know that 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.

Speaker 5

We may see those comments in 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 and pull through them.

Speaker 2

Right. And so maybe you want to make a comment on revumentum as well?

Speaker 5

Yes. And on revumentum, 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 be ready.

Speaker 5

The market is 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.

Speaker 5

We've got about 2,000 accounts that we call in for revhumaniv. There's about 200 that cover 2 thirds of patient opportunity. We prioritize them. So we've taken a very talented experienced sales team. Got over 20 years in the space, many of them have launched products, averages about 6.

Speaker 5

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 KMT 2AR will place. Testing is very high. We're understanding how to pull things through. And then on the payer side, we've been calling in customers for well over a year.

Speaker 5

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 trunking that to the 6 to 9 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.

Speaker 5

Patients are too sick. I think I mentioned the prognosis for patients with relapsed refractory, the KMT 2 AR 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.

Speaker 6

And then Chris, this is Keith. With respect to your question on SG and 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 $31,000,000 for SG and A combined, that will grow as A and P, advertising and promotion costs, increase when we do get approvals and do launch these drugs. But I don't think I think you can 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, etcetera, is fully built out.

Speaker 9

That's helpful context. Thank you.

Speaker 3

Thank you, Chris.

Operator

The next question is from the line of Kelly Hsieh with Jefferies. Your line is now open.

Speaker 4

Congrats on the great progress in the quarter and for the upcoming also very eventful Q4. Firstly, curious your view on the clinical bar for CR, CRH rate for the pivotal MTM1 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.

Speaker 2

Great. Well, thank you, Kelly. I appreciate your kind comments. So in terms of the clinical bar for MPM-one, I think we've been very consistent in our approach here. I think the data for KMT2A and MPM-one so far across all different trials, monotherapy combination has looked very consistent.

Speaker 2

And we are based on precedent, you can look at 20% to 30% CRCRAH rate as the approvable bar, as low as probably 20% could be approvable. But I think it's in terms of what we would expect, we've shown data in that range for NPM1 even higher at our Phase 1 data was at 36%. So we feel very confident that the results will fall in that range and be very, very positive. I think this is a, you know, there's an approval question and then there's, you know, 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 ask Angelie to make a comment.

Speaker 10

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 3 months by the time you're treating a third line patient. It's similar for MPM-one, 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.

Speaker 10

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.

Speaker 11

Good afternoon. Thanks for taking our questions. Two questions from us. So first, the updated KMT2A AUGMENT-1 hundred and one 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 that's what is that what the FDA is reviewing?

Speaker 11

That's first. And then second, we noticed on your slides describing the pivotal trial in combination with Venase in the frontline, there was no rivumedib dose listed. Have you determined with the FDA's input what that dose is likely to be? Thanks.

Speaker 2

Yes, Phil, thank you. 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 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 3 months. We're now 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 could say is this information is highly consistent and supportive of approval.

Speaker 2

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 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 the 13 months on the duration, the meeting duration of response. So some encouraging signs, of course.

Speaker 2

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 he

Speaker 3

can make a comment on it. Yes, go ahead. Yes, sure. So, Phil, thanks for the question. As I mentioned a little earlier, the Health Authority approvals are currently in process.

Speaker 3

In fact, there are several of the submissions have been made in or submissions have been made in several countries, and we're initiating the study at 160 milligrams.

Speaker 11

That's very helpful. Thank you.

Speaker 9

You're welcome. Thank you.

Operator

The next question is from Michael Schmidt with Guggenheim. Your line is now open.

Speaker 12

Hey, guys. Thanks for taking our questions. 2 from us. Just on the KMT2A data, on the 13 month duration of response that you've disclosed today in the ASH abstract and OGN-1 hundred and one, Would you expect a similar duration in NPM-one treated patients once you have longer follow-up from that cohort? And then as we think about the menin inhibitor competitive landscape, And as 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 repumenib over others in the field?

Speaker 12

Thanks so much.

Speaker 2

Okay. So thank you, Michael. Appreciate it. So in terms of duration of response, we did note I did note the 13 month extension on the follow-up there. You know, I think the that is, you know, I think an interesting result, an important result.

Speaker 2

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 HEMPM1 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 you know, time on therapy and, you know, ultimately could impact the duration.

Speaker 2

So, that is, you know, 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, you know, 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. You know, it's, you know, perhaps we can draw some conclusions.

Speaker 2

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, you know, highly encouraging of what we're seeing. These are essentially 4th line patients who have had lots of stem cell transplant and prior venetoclax and to see, you know, extremely high rate of overall response. But even in CRC, CRC RH, 58%.

Speaker 2

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, whereas you saw the last data cut or the last update, first update, I should say, was at ASH last year. So highly encouraging, again, very heavily pretreated patients. We will, we hope to have an update at our investor event on the beta AML trial at ASH.

Speaker 2

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 venes or combos.

Operator

Thanks. Really appreciate it.

Speaker 2

Thank you, Michael.

Operator

The next question comes from Yigal Nochomovitz with Citi. Your line is now open.

Speaker 4

Hi, guys. This is Ashik

Speaker 13

on for Yigal. Thanks for taking my question. Congrats on all the updates here. I just wanted to ask a follow-up on the maintenance setting questions asked earlier for ready manid. I guess, for the AGM-one hundred and one KMT2A cohort is 9 out of 21 patients that that got maintenance therapy, but 3 out of 12 in SAVE.

Speaker 13

I'm just curious if there were differences in the way those studies were run or maybe awareness among physicians that or differences among regarding awareness between physicians in terms of whether or not they could use ready menop in a maintenance setting. And I'm just I'm also just curious to what degree are you aware of how physicians are sort of deciding how when to use rilimumum in the maintenance setting and what sort of decision matrices there are in place today? Thanks.

Speaker 2

Yes. 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 relapsed refractory patients who have had a lot of prior treatment, stem cell transplants, often more than one, venetoclax as well.

Speaker 2

So they 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 and 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.

Speaker 2

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?

Speaker 3

Yes. 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 3 years or more. So, we know and physicians know that as well. I'm not going to reiterate what Michael said.

Speaker 3

It is a it's a complex paradigm that 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.

Speaker 13

Got it. And could I just ask one more?

Speaker 11

Sure.

Speaker 4

Go ahead.

Speaker 13

One more on one more yes, sorry. One more quick clarifying question on the frontline recommended plus benesa study. Looks like the primary endpoint is overall survival in just the NPM1 population. But 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?

Speaker 13

Thanks.

Speaker 2

Yes. Neil, I'll take

Speaker 3

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 you know, I think I also mentioned in the script, this population so think about the population that will go into the study.

Speaker 3

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 KMT population, for instance, from OVMT-one hundred and one, the median age is 35 in the updated analysis that we just talked about, the abstract of which was published today. So KM-two twenty eight is more prevalent in the younger population.

Speaker 3

MPM-one is more prevalent overall and more prevalent than KM-two twenty eight in the older population. In fact, K-two twenty eight is quite rare in the older population, which will include some of those patients as well. That's why it's designed the way it is. That makes sense?

Speaker 13

Yes. Makes a

Speaker 4

lot of sense. Thanks very much and congrats again.

Speaker 3

Thanks, Shik. Thanks, Shik.

Operator

The next question is from Jason Zumansky with Bank of America. Your line is now open.

Speaker 14

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.

Speaker 14

For NPM1, curious as 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 efficiency range or efficacy range. Certainly, you mentioned for physicians, higher the better.

Speaker 14

But is that 20% floor you mentioned necessary for approval, does that still apply? Or is that higher? Thanks.

Speaker 2

Yes. Jason, thanks for the question. So first of all, for MPM-one in terms of breakthrough therapy designation, we had in the Phase 1, we had 14 patients that were at the RP2D, which I think we have been very clear is, is falls, it basically falls short of what's required for submission for breakthrough. So we didn't have the applicable data for, for the, for that designation. So we had not applied at the time.

Speaker 2

And so we are right now running a trial. If we decide, obviously, when 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 tour and other things that advantaged us with came to its way. Having breakthrough as for your second indication is less impactful. So, you know, again, just to be clear, we didn't apply for it.

Speaker 2

It didn't, we didn't have the data from the phase 1 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 the, as I said before, the precedent here, again, these therapies in AML, 20% or higher CRCRA rate, duration of response in the 4% to 6% 4 to 6 month range.

Speaker 2

Those are general parameters that we see other drugs to get approved by. And that's just historical precedent. I think from our standpoint, having a CRCRA trait 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 the, 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.

Speaker 2

We've seen data in Phase 1, 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 MPM1 in terms of transplant rate and how that impacts, potentially impacts the CRCRA trait, which could be favorable in this regard relative to what we see for KMT 2A. So we feel very good, and we'll see the data soon.

Speaker 2

So thank you.

Speaker 8

Great. Thanks.

Operator

The next question is from George Farmer with Scotiabank. Your line is now open.

Speaker 15

Hi, good afternoon. Thanks for taking my questions. Really appreciate your decision to disclose the additional KM2TA 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?

Speaker 2

Yes. Thanks, George. I wouldn't anticipate we're going to update the data set again. I think we have an approval coming and we have NPM 1 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 what it, how it performs relative to all of these measures, whether it's, you know, patients staying on drug, maintenance, what have you.

Speaker 2

And so I think, you know, 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 I just at this point, we're not having we don't have any plans to update the data set beyond what we've already provided.

Speaker 15

Okay. 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.

Speaker 2

Yes. 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 VYALA that was roughly a 4 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, that's, you know, we haven't provided a specific timeline to

Speaker 4

complete the trial just yet. We need to get it started. We'll get it started at the end of the year and then

Speaker 2

we'll get it 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. Okay. And then one

Speaker 15

more, if I don't 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

Speaker 2

term? 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 2.35 times what they've put into the transaction, which, you know, supports and the drug forecast seems it will support that.

Speaker 2

And then some we believe that they looked at all of the indications and the potential indications both in GVHD is 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 are able to attain in this deal for Syndax is quite helpful in support of long term of our objectives.

Speaker 15

Okay, good. Thanks very much.

Speaker 9

Thank you.

Operator

The next question is from Kalpit Patel with B. Riley Securities. Your line is now open.

Speaker 9

Yes. Hey, good afternoon and thanks for taking the question. 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 KMG2AR patients to make sure that they will be included on label?

Speaker 9

Or do you just need to hit the primary endpoint for NTM1 patients?

Speaker 3

Yes. 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 KM220A patients.

Speaker 3

We will be looking for consistency of effect in the KM220A 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 this study is to have the drug approved in combination with FINAZA for MPM-one patients?

Speaker 9

Okay. Got it. And then at ASH, I guess what sort of additional analysis should we expect for the KNP2 AR 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 a baseline demographic? Thank you.

Speaker 2

Yes. Go ahead, Neil. Why don't you? Yes. Look,

Speaker 3

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 ASH presentation. Sorry, I can't be more specific.

Speaker 9

Okay. Got it. Thank you very much. Thank you.

Operator

The next question comes from Justin Vielen with BTIG. Your line is now open.

Speaker 14

Thanks for taking our question and congrats on the progress. So on the revimativ filing, I understand that patients are regularly tested for KMT2A status, but do you expect you'll need a companion diagnostic for approval?

Speaker 2

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 competitive diagnostic.

Speaker 2

But there is, you know, for KMT2A, there are some existing diagnostics available that make, you know, make testing available and robust. So, you know, 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 to that.

Speaker 14

Great. Thanks for taking our question.

Speaker 9

Thank you.

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.

Speaker 2

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.

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