Syndax Pharmaceuticals Inc
NASDAQ:SNDX
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Syndax Pharmaceuticals Inc
Earnings Call Analysis
Q2-2024 Analysis
Syndax Pharmaceuticals Inc
2024 is poised to be a pivotal year for Syndax Pharmaceuticals as they approach what could be a significant milestone: the anticipated FDA approvals for two promising treatments, revumenib and axatilimab. The company has shown strong clinical momentum in the first half of the year and is now on track to become a commercial-stage entity.
During the recent European Hematology Association Congress, Syndax presented encouraging data regarding revumenib’s potential to enhance current treatment paradigms in acute leukemia. Specifically, the results from combination trials demonstrated a high complete response rate, with 96% of patients achieving clinical responses【4:5†source】. In addition, axatilimab's clinical efficacy in treating refractory chronic graft-versus-host disease was reinforced with updated data, illustrating significant patient improvement in symptomatology【4:1†source】.
Axatilimab has a Prescription Drug User Fee Act (PDUFA) date set for August 28, 2024, followed by revumenib, which has been pushed back to December 26, 2024, due to a standard extension for additional review【4:6†source】【4:2†source】. The total addressable market for axatilimab in the U.S. is estimated between $1.5 billion to $2 billion, considering its potential premium pricing and the chronic GVHD market segment【4:1†source】【4:3†source】.
Syndax reported a robust cash position of $455 million, sufficient to fund operations through 2026【4:3†source】. Operating expenses were reported at $77.7 million for the second quarter, with projections for the third quarter estimating total operating expenses at $105 million to $110 million【4:3†source】. Looking ahead, research and development expenses for 2024 are expected to be between $240 million to $260 million【4:3†source】.
Syndax has laid the groundwork for the commercial launch of axatilimab, collaborating closely with Incyte to leverage their expertise in the field. Details released indicate a concentrated effort to cover nearly 2,000 treatment centers, with a significant sales force prepared to address market needs【4:3†source】【4:10†source】. There is cautious optimism regarding the drug's uptake, particularly among academic centers engaged in transplantation【4:10†source】.
Beyond the immediate opportunities, Syndax is actively seeking to expand its pipeline through business development strategies focused on early-stage oncology projects, which indicates a long-term growth vision anchored in continuing innovation【4:4†source】【4:19†source】.
While the roadmap appears promising, investors must remain aware of inherent risks. The FDA's extended review timeline for revumenib does introduce slight uncertainty regarding regulatory outcomes, and adherence to anticipated timelines is critical as both approvals approach【4:6†source】【4:16†source】.
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Good day, everyone, and welcome to the Syndax Second Quarter 2024 Earnings Conference Call. Today's call is being recorded. [Operator Instructions] At this time, I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals.
Thank you, operator. Welcome, and thank you, all, for joining us today for a review of Syndax's second 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 Closter, 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 Business 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. Before we begin, I would 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 the statements as a result of various important factors, including those discussed and 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 may represent our views as of today, August 1, 2024 only. A replay of this call will be available on the company's website, syndax.com, following its completion.
With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.
Thank you, Sharon. Good afternoon, everyone, and thank you for joining us today. Starting with Slide 3. This is a very exciting year for Syndax as we stand on the cusp of becoming a commercial stage company with the anticipated upcoming FDA approvals of revumenib and axatilimab, 2 first-in-class treatments for diseases with high unmet medical need.
I'm pleased to report that we have achieved several clinical milestones in the second quarter that support our strategic priorities. In June, we presented updated positive revumenib combination data from the BEAT AML and AUGMENT-102 trial at the European Hematology Association or EHA Congress. These data, which Neil will review shortly, continues to support revumenib's potential to enhance current standard of care agents.
At EHA, we also presented additional positive data from the AGAVE-201 pivotal trial evaluating axatilimab in patients with refractory chronic graft-versus-host disease or GVHD. Reinforcing the previous organ response data that we had shared, this latest data set shows that responses were noted in all fibrosis dominant organs that had clinical activity, supported by clinician reported and patient reported changes in organ-specific symptoms, such as improvements in swallowing, shortness of breath, pain in joints and sclerotic skin. Looking ahead, we are on track for a historic year with the anticipated FDA approval of revumenib and axatilimab coming soon.
With axatilimab, our anti-CSF1 antibody for patients with chronic GVHD, we have a PDUFA action date of August 28, 2024, and anticipate launching in the fourth quarter of this year with our partner [ insight ]. With revumenib, our menin inhibitor being reviewed by the FDA for patients with relapsed or refractory KMT2A-rearranged acute leukemia, we have a PDUFA action date of December 26, 2024, As we announced earlier this week, the FDA recently extended PDUFA action date for revumenib NDA from September 26 to December 26, 2024, a standard 3-month extension to allow for additional time to conduct a full review of supplemental information we provided in response to their request.
Importantly, we are confident that the information we have provided to support approval and continues to demonstrate the meaningful benefit revumenib brings to patients. We look forward to continuing to closely engage with the FDA as they complete their review under the Real-Time Oncology Review program or RTOR, and we stand ready to launch revumenib with [ strength ] as soon as we receive the anticipated approval. Later in the call, Steve will provide some additional color on our preparation for these 2 anticipated launches.
We also have several other meaningful milestones approaching such as the anticipated readout of pivotal top line revumenib data in relapsed/refractory NPM1 AML in the fourth quarter, which could serve as the basis for a supplemental NDA filing in the first half of 2025.
Additionally, we expect to make further progress advancing our clinical trials of revumenib and axatilimab that are underway or planned to initiate in the coming months. Positive results could support the future use of these agents in combination with standard of care medicines earlier in a patient's treatment and thereby expand their utilities significantly.
We are in a strong financial position with $455 million in cash as of June 30th that we expect will provide sufficient capital through 2026. Our current balance sheet not only supports our planned commercial launches and clinical trials, but also sets us up to expand beyond our first registration indications and to pursue early stage business development opportunities.
I'll now ask Neil to review some of our recent data presentations and pipeline. Neil?
Thanks, Michael. Turning to Slide 4 in revumenib. We have a robust clinical development strategy underway that will support the use of revumenib in KMT2A rearranged and mutant NPM1 acute leukemia across the treatment paradigm. The development plan extends beyond the initial [ relapsed ] [ or ] refractory indication with trials of revumenib in combination with standards of care that potentially support use in the frontline relapsed [ or ] refractory in post-transplant maintenance [ with ] [ revumenib ].
On the next 2 slides, I will briefly review the data recently presented at EHA from the 2 combination trials that we delisted, BEAT AML and AUGMENT-102. On Slide 5, at EHA in June, we and the collaborators of the Leukemia Lymphoma Society presented updated data from the BEAT AML trial of revumenib in combination with venetoclax and azacitidine or ven/aza in patients newly diagnosed with mutant NPM1 or KMT2A rearranged AML. This updated data sets with the cutoff of the 1st of May 2024, [ and ] [ 24 ] efficacy evaluable patients, 96% of patients with [ composite ] complete [ response ] or CRC and 92% with no residual disease and were therefore MRD negative.
As in all the combination trials conducted so far, 2 doses of revumenib are being investigated, 113 milligrams and 163 milligrams administered every 12 hours. The dose limiting toxicity or DLT window for each [ were ] [ carried ] last year on this trial, and both cohorts are currently being expanded in order to identify the dose Phase III development. The combination is well tolerated and the safety profile reported at EHA is consistent with what has been previously reported.
Of note, the rates of adverse events associated with the combination of revumenib ven/aza observed in the study are consistent with data for ven/aza from historical controls. For example, the addition of revumenib to the [ doublet ] does not appear to exacerbate the modest depression associated with ven/aza alone.
Additionally, the BEAT AML investigators [ computed ] that the data suggests that adjusting the dose of venetoclax while maintaining the doze for revumenib may be the methodological strategy for future development. As we've previously communicated, we intend to initiate a pivotal trial with the scripted combination in newly diagnosed patients by year-end.
Turning to Slide 6. At EHA, we also presented updated data from the AUGMENT-102 trial of revumenib in combination with fludarabine and cytarabine or FLA in a predominantly pediatric population with relapsed [ or ] refractory mutant NPM1, NUP98 rearranged or KMT2A-rearranged to AML. As of the data cutoff of 15th of January 2024, 27 patients received FLA with revumenib at 113 milligram or 163 milligrams.
Patients included in the trial were heavily pretreated with a median of 3 prior lines of therapy, 67% of prior FLA-containing [ regimen ], 52% of patients achieved composite complete remission or CRC. The MRD negative rate among CRC patients of 71%. Furthermore, certain patients or 50% of responders proceeded to transplant once they had [ entry ] permission.
As with the ven/aza triplet, we just discussed revumenib does not appear to alter the tolerability profile of the standard of care regimen. These 2 updated data sets presented that EHA further -- provide further support for combining revumenib with different standards of care in the newly diagnose as well as relapsed or refractory [indiscernible].
Turning to Slide 7. In March, we completed enrollment in the pivotal cohort of the AUGMENT-101 trial with the enrollment of 64 adults and also 20 pediatric relapsed or refractory NPM1 mutant AML patients. We are on track -- our acute leukemia patients. We are on track to report data in the fourth quarter.
On this slide, you can see the results from 14 mutant NPM1 patients in the Phase 1 portion of AUGMENT-101, which showed that 50% of patients achieved a response from -- 36% achieved a complete remission or CR with partial hematological recovery. Notably, all patients with the CRC rates were MRD negative. And consistent with the KMT2A population, revumenib also enabled patients in remission to proceed to transplant with a durable response despite many of the patients having [indiscernible] prior venetoclax therapy and cell transplant.
These data also indicate that revumenib is well tolerated in patients with mutant NPM1 with an overall safety portfolio that is consistent with what has been previously reported in the KMT2A-rearranged population.
Before I hand over to Steve, I'd like to provide a quick overview on Slide 8 of the preparations we've made and the medical side of the organization to support the upcoming anticipated launches. We've built a highly experienced medical affairs team that is driving deep scientific engagement and robust evidence generation. As you've seen from our participation in ASH and EHA as well as various papers and top-tier journals such as Nature, we have an ambitious conference and publication plan underway to increase awareness of the compelling data from our 2 agents.
We also continue to prepare for NCCN guideline submissions for revumenib that we anticipate will include the prescribing information as well as peer-review publications and congress presentation. Of note, once the top line data in mutant NPM1 AML are available, we plan to publish as soon as it's feasible to support potential guideline inclusion following the approval of revumenib and KMT2A.
Additionally, we have a team of seasoned medical science liaisons in the field. They've made a tremendous progress driving scientific exchange, which positions major centers of excellence across the country. We also built a health economics and real-world evidence team focused on supporting the value of our portfolio, and we continue to increase engagement with patient advocacy groups.
With that, I'll now turn it over to Steve to talk about our commercial launch plans and the market opportunities. Steve?
Thank you, Neil, and thanks to everyone for joining us today. We really appreciate it. It's really a pleasure to be with you to talk about the extensive preparations we're making to position Syndax as a leading commercial stage organization serving patients and health care providers. We are well prepared to execute on the exciting opportunities in front of us.
Turning to revumenib preparations in Slide 8. Our goal simply is a strong launch, and we are ready to hit the ground running with revumenib as soon as we receive the anticipated approval from FDA. We've hired and trained a sales team with extensive experience and pre-existing relationships in hematology, oncology space and a demonstrated track record of success. This team is in the field right now [ for ] filing accounts and understanding the patient treatment journey so we can meet the needs of the different stakeholders involved in their care.
This robust pre-launch preparation will let us rapidly begin meeting patient needs upon the anticipated approval. Our customer-facing team has an average of 22 years of experience, primarily in hematology, oncology and an average of 6 product launches each. With an efficient field force footprint in the range of 30 to 50 individuals, we believe that we can effectively reach the relevant academic and community-based centers and meet the needs of physicians and patients. We plan to call on approximately 2,000 centers with roughly 200 of those accounts representing more than 2/3 of the opportunity, enabling a concentrated effort. With our plan, we believe we should reach centers with 98% or more of potential relapsed/refractory KMT2Ar patients receive treatment.
Now another important thing we've done in preparation for the launch is to develop advanced data mining capabilities to appropriately identify patients need. Because these are high-risk patients that require rapid identification of the treatment options, we've developed capabilities that will help us initiate very targeted physician engagement based on where our tools indicate there are appropriate patients.
Now with respect to market access, we've built an accomplished team with extensive experience working with payers and other trade partners to facilitate access to new products. Together with the medical affairs team, our payer field team continues their pre-approval information exchange work with payers, and we're on track to reach plan, covering more than 90% of all covered lives both commercial and [ Part B ] prior to the anticipated approval.
Payers tell us that they recognize the unmet need and appreciate the value that revumenib provides. We believe plans will make their formulary decisions within 6 to 12 months of approval, and we'll work with them to expedite the review when possible.
Importantly, given the urgent patient needs, we expect that plans will provide patients access to the product at launch through the medical [ exception ] process to support providers and patients we've partnered with, leading best-in-class specialty pharmacies who are well recognized for their ability to help providers and patients navigate access to new oncology medicines.
Through a network of specialty pharmacies and specialty distributors, we're prepared to have product and channel very quickly right after we receive approval. We're also ready to launch a dedicated patient support program that will provide a level of support on par with what you see from leading oncology company.
Turning to Slide 9 in the market opportunity. KMT2Ar and NPM1 acute leukemia represent up to 40% of all AML patients. There are no FDA approved targeted therapies for this population. We believe relapsed or refractory KMT2Ar acute leukemia alone represents a [ totable ] addressable market opportunity of approximately $750 million in the U.S. The annual incidence of KMT2Ar acute leukemia, about 2,600 patients with the majority of these patients, about 2,000 experiencing relapsed or refractory disease. We estimate a median duration of therapy across the treated population of approximately 9 months, and we believe the clinical data supports pricing competitively to other targeted therapies in AML, such as [ FLT3 ] or IDH inhibitors.
Physicians we've spoken with indicate an eagerness to prescribe revumenib early during an eligible patients treatment journey to bring more patients to transplant and then extend responses by continuing with revumenib monotherapy following transplant engraftment. We expect that our first mover advantage and the early experience physicians will gain treating patients with revumenib will be vitally important for the long-term success of our brand.
Our significant market share is likely to extend meaningfully beyond KMT2Ar, especially as we will be the first to deliver meaningful pivotal data in other indications, such as NPM1 AML. We estimate that the 2 distinct market segments in acute leukemias, KMT2Ar and NPM1 equal a combined accessible population of [ 5,000 to 6,500 ] patients in the relapsed or refractory setting and an addressable market opportunity that approaches $2 billion in the U.S.
During the various meetings that I've had the chance to participate in with clinicians, from advisory boards to field business and more, I've seen tremendous excitement and support for revumenib creating a momentum that I look forward to, building on to our commitment to delivering an absolute best-in-class experience for health care providers and patients.
Moving to axatilimab on Slide 10. The anticipated commercialization of axatilimab will be led by the Incyte site team and we'll benefit from the deep experience and long-standing relationship that they've established through their work, building the GVHD market with Jakafi. We'll provide 30% of the sales effort, leveraging our own field force that we anticipate will carry 2 products with highly overlapping call points.
Paved the way for a successful launch, Incyte is continuing to drive engagement with payers and raise awareness of the distinct pathway that axatilimab targets and the compelling outcomes observed in the AGAVE-201 trial, which we recently detailed at the 2023 EHA Congress.
Turning to Slide 11. We estimate there are approximately 17,000 patients on treatment for chronic GVHD at any one time, the majority of whom are refractory and cycle through therapies for better symptom control as their disease progresses. We believe there are approximately 6,500 patients progressing to later lines of treatment after 2 previous lines of treatment, which would be our target population for our first indication and represents an attractive initial opportunity. For instance, in the 3 years since the launch of Rezurock and other drug with a third line indication, net sales continue to grow, and they're annualizing at nearly $500 million.
We estimate that the total addressable market for third line treatment in the U.S. is between $1.5 billion to $2 billion, which assumes that patients will remain on therapy for over 12 months and assuming axatilimab is priced at a premium to approved agents for chronic GVHD, based on its product profile and Part B reimbursement. Beyond the third line setting, we plan to study axatilimab in earlier line settings for chronic GVHD and other diseases where we believe it's anti-fibrotic and anti-inflammatory mechanism is relevant, such as IPF, which represents a large opportunity.
I'll now turn the call over to Keith to review our financial results.
And thank you, Steve. Turning to Slide 12. As Michael mentioned earlier, the $455 million in cash equivalents and short and long-term investments on our balance sheet as of June 30, we expected to provide runway through 2026. Our financial strength allows us to fund the anticipated commercialization of 2 drugs and appropriately invest to continue to realize the value of our pipeline.
Turning to the income statement. Operating expenses in the second quarter were $77.7 million and included $48.7 million of research and development expense and $29.1 million of selling, general and administrative expense. Let me provide financial guidance for the third quarter and full year 2024.
For the third quarter, the company expects research and development expense to be $70 million to $75 million and total operating expenses to be $105 million to $110 million. For the full year of 2024, there is no change to the existing guidance, and the company expects research and development expenses to be $240 million to $260 million and total operating expenses to be between $355 million to $375 million.
Please note that the guidance range for operating expenses for the full year includes an estimated $43 million of noncash stock compensation expense and that research and development expense guidance includes any milestones owed to our partners [ on ] potential drug approvals.
Ahead of the upcoming launch of axatilimab, I want to briefly review how we will recognize revenue for that partner product. Slide 13 provides an illustrative example of accounting for sales of axatilimab and is not intended to provide any margin or any other guidance. We will record 50% of the commercial profit defined as net product revenue minus the cost of sales and commercial expenses. During a period where there is net commercial profit for axatilimab, as in the top example of this slide, our 50% share of the net profit will be recognized on our P&L as collaboration revenue.
During a period where there is a net commercial loss for axatilimab, as in the example on the bottom of the slide, our 50% share of the net commercial loss would be included in operating expenses designated as a separate line item called share of collaboration [ loss ]. The milestone revenue from various global commercial and regulatory milestones that we received from Incyte will be recorded as a milestone revenue on our income statement.
As a reminder, research and development expenses under our partnership, including regulatory and CMC expenses were shared [ 55%-45% ] in the U.S., and our 45% share is included in the income statement as part of our R&D expense. Outside of the United States, Incyte is responsible for 100% of the development and regulatory expenses, and we are entitled to receive milestones with a double-digit royalty on ex-U.S. sales.
With that, let me turn the call back over to Michael.
Thank you, Keith. As you heard during our call, we have made tremendous progress over the past few months and are well prepared for the transformational period ahead of us with the anticipated FDA approval and launch of our first 2 medicines. With the momentum we have built and our robust clinical development strategy designed to explore the full potential of revumenib and axatilimab, we are excited about the path ahead and the opportunity we have to make a major impact for patients.
On Slide 14, you can see a recap of our upcoming anticipated milestones that we believe we will continue to fuel our momentum and drive value. As always, I want to express my gratitude to the Syndax team and our partners for their hard work and dedication to our mission. Most importantly, I want to thank all of the patients, families, trial sites and investigators who have participated in our trials and inspire us with their tenacity and commitment to finding new ways to improve the lives of patients with cancer. I'd also like to thank our committed long-term investors who continue to share in our vision and support our work building Syndax.
With that, I would like to open the call for questions, operator.
[Operator Instructions] Our first question comes from Anupam Rama from JPMorgan.
This is actually now from Malcolm Kuno for Anupam. Can you remind us of the size and scope of the field force? And then what sort of medical education efforts will you have ongoing ahead of the potential axatilimab and revumenib approval?
Thanks for the question, Malcolm. Let me turn it over to Steve to address it.
Yes, thanks, Malcolm, for the question. In terms of size, I think like comments in the opening was roughly 30 to 50, sorry for the wide range. We haven't given an exact number. But it's adequate to cover the audience. We've got overlapping field teams. I mean it's a complex treatment journey for patients. They've got treatment centers that have physicians and nursing staff and lab in pathology and formulary. So we've got different customer-facing teams to cover that. We'll cover, I think I said 98% of the opportunity. So it's in place. The field team is activating.
I think your other question was around education and what are we doing. I'd say for the field right now as an organization, we're really trying to do 2 things. One of them is profiling accounts, I mentioned that the complex treatment journey. We want to understand for any given institution that we call on, on how they do business, how they see patients, how they're treated. There's a ton for us to learn from understanding how to [ touch for ] KMT2Ar, how those patients get highlighted for clinicians, how they like to deliver drug, the role of nursing staff.
So of the 2,000 accounts that I mentioned, we've already been to more than half of them. I also -- I think I mentioned that we call it about 200 that are the priority accounts. We've been to probably at this point, 85% of them and in some of them we've made multiple calls. So that's one thing we're doing, and that's profiling accounts, and the goal is to, at the time of launch, know everything that we need to know in order to get patients on drug and treat it.
Second piece is the education piece. There is a little bit of a lift here for menin inhibition from the mechanism of disease standpoint. So that is something else that our field teams are delivering. We've also got a [ non ] personal effort really to raise awareness. Clearly, [ not ] talking about the drug, at least from a commercial standpoint but are raising awareness of the mechanism, we're the only one that's going to be out. So the awareness level should be tied by the time we get to launch. So between profiling, raising awareness, we'll be in great shape once the drug gets approved to pull it through.
Our next question comes from Chris Shibutani from Goldman Sachs.
This is Kevin [indiscernible] on for Chris. Just wanted to talk about the combination studies for revumenib in the second half. You said you'd have data updates. Could you just highlight in bookend what those will be? I believe there's going to be an update from the safe trial?
And then also for the BEAT AML trial, can you talk about where you are with respect to establishing a recommended Phase II dose there? And then what the rate limiting steps are to start that pivotal trial by the end of the year? And then potentially, how many doses you could bring forward into that trial?
So Kevin, maybe I'll address that. So for the BEAT AML trial -- the BEAT AML trial, I'll start there. As you know, we're looking for a recommended Phase II dose. We've made tremendous progress at EHA, we had presented the data on both of those doses. We have in the process of filling out -- at least those 2 doses just filling out the expected number of patients, and we're going to be making a choice at some point soon between the 2 doses, which is the recommended Phase II dose, we'll be working through that over the next weeks. So we're in very good shape, ultimately, to start a trial, we believe, by the end of this year, pivotal trial. And so stay tuned for additional updates on that as we get through the year.
In the safe trial, we -- again, this is Dr. Guise's trial at MD Anderson. This is in relapsed/refractory patients. Combination of [ ven ] and [ cobi ] plus revumenib. We presented -- data presented last year at EHA -- sorry, at ASH. So the investigators told us that there will be some updated presentations in the latter half of this year. But of course, we're not at liberty to say exactly where that is at this time.
But we do expect there to be more patients, additional follow-up. And as you know, it was exciting data. So we're eagerly anticipating that as well.
The next question is from the line of Phil Nadeau from TD Cowen.
This is [indiscernible] for Phil. I have 2 brief ones. The first one is, even though [ there ] are [ lot ] in the target treatment centers within revu and [ ax ], and all the prep work -- commercial prep work that you've been doing, do you see any benefit to the now sort of like delay or longer time between the 2 launches? Like can you see perhaps that maybe a benefit or any learnings that you can use to later accelerate the launch? It came too late relative to what your internal estimates were?
And then the second question is, for the INTERCEPT trial of revumenib in monotherapy in the maintenance setting, I believe that trial has been ongoing for a while. I was wondering if there's any updates there, or when could we see data from that trial?
Thanks for the question. First, I'll ask Neil to address the trial question that you asked, and then Steve will address your commercial question.
I think you were asking about the INTERCEPT trial. So you're right, the INTERCEPT trial has been ongoing for some time. The trial is progressing well, as you are also well aware, it is a third-party firm, therefore we don't control disclosure of data. But our understanding is that recruitment is going relatively well. And we expect that the investigators will present data at a medical meeting in the future, but we don't have an exact planning on that.
With that, I'll pass it over to Steve for your first question, [ actually ].
Yes. So just to reiterate, the first question was really sort of benefiting the extra time, particularly the overlap of the 2 compounds. So I think just speaking, and really speaking from experience, there's never been a launch where someone -- in terms of the pre-launch period, they wish they had less time or more time in advance of an approval. I think the answer is always, they wish they had more time. So we obviously have more time in revumenib than we would have otherwise anticipated.
The activity that I've described before will enable us [ all ] the profiling and the mechanisms of disease and disease [ state ] awareness work we're doing. We'll put to good use over the -- however long it takes us to get to approval. And the 2,000 accounts that I mentioned, there's a good chance we will be at all of them, if not most of them, and we'll be there multiple times. So I think that we'll be -- we'll have -- we'll be able to leverage all that time.
And I think the point made, there is tremendous overlap with the axatilimab opportunity. I don't think I shared the number of treatment centers for chronic GVHD, but we essentially covered them all by covering all of the revumenib opportunities. What I mean by that is 2,000 centers, both academic and community that we're covering [ off ] right now in revumenib, there's under 200 that you'd cover for transplant to support axatilimab.
So we're early in those, essentially, so we're profiling those accounts as well. There's a lot of connectivity between [ hema ] and transplanters, and there's actually some advantages with rev, particularly as patients hopefully move to our transplant and potentially go on continued treatment.
So we've always seen that strategically, both drugs are highly aligned to what we're trying to do as an organization. The call point -- it's the same call point. So we can really accomplish both, and we'll, like I said, make use and leverage the time we have for now, so, [ given ] product comes to market.
Our next question comes from the line of Peter Lawson from Barclays.
This is [ Alex ] on for Peter from Barclays. Just a quick clarification for me on the BEAT AML study. Do we see more data from this study later this year? And then a separate question is, do we see -- can we see initial Phase I data from your 7 [ plus ] 3 combination in 2024?
So for BEAT AML, I think we had obviously mentioned that this is not our trial. We are collaborating closely with the sponsor. But the last update was done at EHA, so that was a pretty comprehensive update. We don't have knowledge yet when that's going to be updated. It's possible it could be -- it could come in the second half of this year at one of the medical meetings. But we don't have perfect information there. So stay tuned on that.
And then for the 7 [ plus ] 3 Phase I that we've initiated, we haven't given guidance yet as to when we're going to be putting together the initial data for that. So stay tuned. I wouldn't expect that we would have it in 2024. That's likely to come in 2025.
And just if I may a quick follow-up. Do you have to enroll sort of adverse risk patients here initially? Or what types of patients are being enrolled in the Phase I?
Yes. I don't think we've actually talked about the exact type of patients that we're enrolling in the trial. I think they're just newly diagnosed patients that -- with 7 [ plus ] 3 in combination.
Our next question comes from the line of Brad Canino from the CFL.
This is Brad. I think it would be good to clear up some of the sequence around revumenib review. I think a lot of us presumed that with RTOR and the closed FDA collaboration of that revised plus you're [ ramping ] commercial and vocal about it, that you had really good visibility about what you needed to get this across the line, either at or well before the PDUFA. So can you help us understand a bit of what happened here?
I think we were able to catch up with many of you earlier in the week when the news came out. Look, I think this is unfortunate in the sense that we were in receipt of a few RFIs from -- and this is an ongoing process under RTOR that's been going on since last year where we submitted our NDA. And since then, we've been receiving requests for information from the agency.
The 2 -- I'd say 2 latest RFIs were -- resulted in quite a bit of information going back to the agency. Once they received that information, they let us know as of last Friday -- late last Friday that, that would require them to actually spend more time on the supplement information and they were going to extend the clock under a major amendment. That's a 3-month delay.
So that was -- and you're right, we were actually quite collaborative over many months with the agency and have been working very closely with them. The information that we provided, we believe, could have been reviewed within the time of the PDUFA. And so for us, we were quite confident that, that was the process that we were following. We were a little bit surprised that the agency would extend the clock, [ but ] they did. That's up to them. That's their decision.
So look, this is information that -- as I previously said, this is information that we did not have in the NDA. It was not requested of us at the time of the submission of the NDA. It was new information -- new clinical information that they wanted to review, and so we provided that. This was something that we were prepared for, but they didn't ask for it and we provided it when they did ask for it.
The only unfortunate part of this is they -- not that they asked for it, but we learned about it sort of late in the review cycle. We had gone through our mid-cycle and our late-cycle review, and it was without event. So we were feeling quite confident in everything that we had not only been through with the agency, but what we submitted in first half. So that's the -- those are the sequence of events, and we feel very confident that this drug will get approved on the December timeline as they've extended the date. So we're in, I think a very good position to launch the drug before the FDA.
And maybe just to follow on that, because I think many of us are now looking at a situation where there's a potential for heightened asymmetry of information. You've got the FDA potentially looking at data that we haven't been able to vet. I guess, what assurance can you give that the overall profile that we know publicly from revumenib is consistent and that prior data cut remains reliable?
Look, I think the information -- and I can -- we don't get into the specifics of anyone's RFI and what's being asked of us in an ongoing review, but what I can say at the late-cycle review, we did learn that there's going to be no AdCom for the product, and they assured us no [ REMS ] program for -- that will be required as well. This is not manufacturing information that they've looked for. It's a clinical package that is in our mind completely consistent and supportive of approval. This is not information that changes the profile [ or ] the risk-benefit at all.
And so, we feel actually it's even more robust of a package than as previously worked on. It's basically what the agency had asked for, and they asked for supplemental information. So we feel like it doesn't change anything at all having to do with the profile or the risk-benefit, and for that reason, that's why we're so confident that the drug will not only get approved, but it'll get approved on the timeline as proposed. So I think that's as detailed as I could get pretty briefly.
The next question comes from the line of Michael Schmidt from Guggenheim.
Maybe just a quick follow-up. So given the revumenib NDA, obviously, is still under RTOR review, and with the extended PDUFA date until end of September now giving half a time for the FDA, just wondering what your view is on the potential for an approval to come ahead of that extended PDUFA date? Is that still on the table, in your opinion? And then I had an unrelated follow-up.
It's not unprecedented for -- either with the extensions. We've seen a couple of RTOR products, Rezurock being one that got approved under RTOR, got extended and actually got approved about 6 weeks earlier than their extended timeframe or their extended PDUFA. So we've seen RTOR products get extended and get approved. Many products under priority review, same thing.
Most of the time they go the distance, meaning that they're approved on or around their extended PDUFA date. It's very hard to know if that will or will not be the case for us. We do expect it to be on or before, of course, but we can't -- it's very hard to judge whether -- that's very removed from the extended date itself. So our expectation is that it will come on or before -- on or around the date that they have specified.
And then, unrelated follow-up, just sort of thinking about the upcoming registration data in NPM1 patients later this year. In -- Perhaps relative to KMT2Ar, how should we think about the transplant dynamics in the NPM1 subset? And related to that, what's a good modeling assumption for duration of therapy for that market subset relative to KMT2Ar?
Thanks for the question. Look, I think NPM1, our view has been all along that the NPM1 data that we've seen in the Phase I trial looks very similar to what we've seen with KMT2A and the consistency across all the measures between the datasets. So that also includes what we've seen in transplant. And although the patients in the NPM1 cohort tend to be a little older, perhaps considerably so, I mean, versus KMT2A, we've also seen a good proportion of those patients get transplanted.
So while the way the patients are treated by physicians, there may be more of an urgency to take patients to transplant who have KMT2A versus NPM1. It doesn't preclude a physician from thinking in the same way, that they're healthy enough and they've cleared their tumor to get them to a transplant. So again, that dynamic has seen -- and we've seen that with NPM1 as well as we have with KMT2A.
So our view is that the modeling assumptions, and of course this is your own model, but we would model them very similarly in terms of percentage of patients who go on to transplant and then potentially even go back on drug post-transplant, even though they happen to be a slightly older patient population. So I think that's to the best of our knowledge based on information that we've seen from the Phase I and now in our pivotal trial for KMT2A.
Our next question comes from the line of Kelly Shi from Jefferies.
Hi, this is [ Clara ] on for Kelly. So now that you will likely have pivotal data readout in NPM1 that had approval in KMT2A, how would that possibly change your discussion with [ NCCN ] [ and ] [ Committee ] for the Guideline Inclusion? And maybe one step forward also, what will be the conversation with payers going to be like upon this update as well?
Thanks for the question. Look, I think the cadence of events here in our mind seems to be that we will have NPM1 data now on our pivotal trial ahead of our KMT2A approval. They'll be in close proximity to one another, but it's no longer the other way around. So having NPM1 data first, our priority will be to get that data published as quickly as we can. And once the drug is approved in KMT2A, we can proceed with potential guideline inclusion for NPM1. So that's the sort of cadence here.
And there'll be some urgency to move in order to [ affect ] the fact that we have a drug on the market and then another indication in NPM1, which is moving through quickly through an [ SMDA ] process at the same time, but could be included in guidelines ahead of approval.
So there will be quite a bit of activity related to not only getting the drug approved, but also moving guidelines through publications and conversations with thought leaders who work on an ad hoc basis, if you will, to get new drugs included in guidelines. Maybe I'll turn it over to Steve to talk about the other questions.
Yes. I think part 2 is what is the impact on payers of NPM1? So, in my opening comments I talked about our activity with payers, which has been expensive. We'll have talked to payers that cover 90% of managed care lives in both commercial and [ Part B ]. I think payers, they recognize the unmet need in KMT2Ar, and they recognize this in NPM1. They like what they've seen with revumenib, and given the price point in the case of roughly $27,000 to $32,000 a month, we believe we'll be at a slight premium to those agents. It's this obvious connection between NCCN guidelines payers.
Payers like to see what's in the public domain. They want to see data published. They want to see the guidelines. Clearly, the entree point is KMT2Ar. That's where we'll set price. I think payers want [ to ] service patients. They'll produce some hurdles and obstacles upfront and barriers, which they always do with products like this. We've got fantastic specialty pharmacy partners and distributors and a patient portal when needed to usher patients through the early days of a launch when products are not yet on formularies.
So we understand the medical exception process as well as our preferred pharmacy partners as well as [ treaters ] and institutions. So we think either way we'll be able to set the right price, and we'll be able to get patients on drugs with some challenge, but we'll get there, and we're prepared to do it.
Next question comes from Yigal Nochomovitz from Citi.
This is Ashiq Mubarack on for Yigal. I just wanted to ask one on axatilimab. Sounds like everything is on track with the PDUFA, which is coming up pretty soon. I just wanted to know if you could share any color on maybe where things are in the sort of [ ELA ] process? Have you reached label negotiations? Was there anything of value with the mid-cycle review? Anything to sort of confirm that [ ELA ] is on track would be very helpful.
Thanks for the question. So we don't comment on any specific part of our negotiations or discussions with the agency during the process. It is under priority review, as you remember. As we said along, it's going well. We do expect the drug to be approved around the PDUFA date, which is the end of August. Nothing that we've encountered in the review process changes that point of view. I won't comment specifically around whether we are or we are not in label discussion, but we are feeling very confident that the drug will be approved and will be approved on its timeline.
Maybe one follow-up on that then. Should we sort of expect the commercial launch to take place maybe immediately after a potential approval that's coming up? Or is there a reason to sort of think there might be a little bit of a lag maybe waiting for a revumenib? So there's some synergy with that commercial launch as well?
So no, thanks for the follow-up, Ashiq. We said that the launch is expected in the fourth quarter. So that's our guidance. We're working with our partner to get ready to do that, and we'll launch the drug when it's ready.
Our next question comes from a line of Kalpit Patel from B. Riley.
Maybe one for revumenib. Is there anything that you learned from the KMT2Ar regulatory filing here that could be beneficial for the NPM1 filing and help streamline that? I know that the timeline says first half '25 and sort of maybe first quarter '25. Is there a reason for that? And then I have a follow-up.
Let me turn it over to Neil to maybe take a crack at that.
Yes. Thanks for the question. So the straightforward answer to your question is yes. So I think that we've learned a lot about the process. And, of course, it's important to draw the distinction between the NDA and the SNDA. So in the NDA, we do a lot of the heavy [ lifting ] is done, and any subsequent application -- supplementary application is much more straightforward. So we're obviously excited and looking forward to getting the NPM1 data during the fourth quarter, and you can be sure that we will be filing or submitting those data as expeditiously as possible.
There was probably a question I missed. Did I address all of your questions, or was there something I missed?
Yes. It's just that -- it's just first half '25 instead of first quarter '25 for filing for the NPM1 cohort?
Yes. We haven't been that specific with our [ guidance here ], [ actually ], you can be sure that we will be working pretty hard at it. I'll put that -- I'll pass it back to Michael.
Kal, your second question?
Yes. So -- and then the second question is sort of related here. Was there -- the new information that was requested by the FDA, I guess, was any part of the NPM1 cohort data set that was sent to the FDA for this update?
No, Kal. But I would actually just focus on the KMT2A submission. That's what we're working with the FDA. And now NPM1 data hasn't even been -- we're not even through the trial. All of it hasn't been done yet. So when that trial is available or when the data is available, we'll publish it, and that will be in the fourth quarter. So you should -- the information that we're focused on with the agency relates to KMT2A.
Our next question comes from the line of Justin Zelin from BTIG.
Michael, I'd like to clarify regarding your confidence on the revumenib approval by the end of the year. Should we continue to expect a traditional approval here, or could there be a scenario in the review cycle where revumenib could be approved under an accelerated approval basis?
I don't think you should assume for a second that this is going to be approved in any other way other than full approval. All of the precedent drugs that have gotten approved in AML as monotherapy targeted therapies have been in the -- through the exact same process. And so, that's never been discussed with the agency that we would -- there is no accelerated approval pathway, and that's not the pathway we're pursuing here. So I would not assume that, that would change at all. And we have high confidence that this is just a delay of 3 months. It doesn't change the process at all in terms of what we're filing for and what we're likely to have at approval.
The next question comes from the line of Jason Zemansky from Bank of America.
This is Cameron Bozdog on for Jason. Congrats on the progress. So looking ahead to the potential near-term launch of axatilimab, can you maybe comment on your internal market analysis and what you've been hearing from prescribers? I mean, do you expect uptake, at least initially, to be largely driven by academic prescribers centered at transplant centers versus community blocks, especially when you think about the [ RTOR ] administration?
Thanks for the question. I'm going to turn it over to Steve to address it.
I'd start off saying, it's a pretty small audience and there's a lot of [ high science ] and experts in the field of transplantation. So it's -- from a treatment center standpoint, I think I may have provided the numbers earlier, 10% of the centers. It's under 200. So it was all driven by that. I think in the part of who's the drivers, academic versus community, it's, the biggest centers are going to drive all this. For the most part, certainly at launch, there'll be some awareness outside of that. And even within the [ 200 ] center, there's probably 35 that see half the patients in the country.
So it is -- I wouldn't say it's the smallest physician audience to call in, but it's one of the smallest. And it's a tight community. I think speaking to market opportunity, there's a lot of business here. There's a lot of unmet need and dissatisfaction in the current treatment GVHD population. They want more. They need more agents. It's a really [ insidious ] disease. So it'll be -- I'd say early uptake and a group of patients probably that are waiting for something like this. It's not a huge number, but there's some number of patients waiting. So there will be some form of [ bolus ], but the market's ready and will be ready shortly too and I think it'll be well received by physicians and patients.
And our final question comes from the line of George Farmer from Scotiabank.
This is Chloe [ Zhang ] for George. So 2 from us. So based on your initial data package for revumenib, so you said that FDA did its thing and [ ODAC ] was necessary. Do you still believe now to be the case? So how confident are you that the additional information you submitted that prompted the proof extension will not be subject of [ ODAC ] review in the next 6 months?
And the second question is, Michael, you mentioned [ BD ] remark. So I'm just curious what types of [ BD ] deals you had in mind, any examples of areas of interest, those types of assets [ you're eyeing ]?. So at the moment, those are the vital or even a target. And if you could maybe put it in context to do the [ Incyte ] relationship for us and tell us kind of how you see that evolving over time?
Thanks for the question. So first, in terms of ODAC, I think high degree of confidence that an ODAC will not be required. The agency on more than one occasion has told us this. The data that we submitted, as I referenced earlier, is only in our minds and very clearly supportive of approval and only augments the package that we've submitted. So there's really -- there is, in our minds and based on what we've heard from the agency, there doesn't seem to be any risk of an ODAC that we know. So I feel quite confident about that.
And then in terms of [ BD ], which is an interesting question and essentially relates to how do we [ grow ] the pipeline and continue doing what we do well at Syndax in part, which is in licensing or acquiring new molecules to add to the pipeline. And we've said in the past that we continue to work on adding or backfilling the pipeline as early-stage molecules in the targeted therapy space in oncology, focused on oncology.
We don't speak specifically about which mechanisms we're going after or the status of any of these discussions and what -- when we conclude our deals, we usually bring -- we do bring them forward and talk about them publicly. But at this stage, we are very actively looking and feel quite good about the potential. But at this point, it's hard to speculate on business development transactions until they're done and closed.
So -- but whatever we do will be a -- it seems of an earlier variety, so we're not looking to take on late-stage projects. Earlier projects are the type of the -- type and complexion of what we feel like we can accommodate at this time with all the other interesting things we have going on in our pipeline for axatilimab and for revumenib. So it's a balanced strategy and one that we are actively engaged in.
With respect to the partnership with Incyte we have been seeing, any thoughts on how you see that evolving in the future?
Our partnership with Incyte is a good one. We conceived it back in 2021 when we announced that. They've been good partners to us. And as Steve outlined and we've talked about, we're keen to launch that, get that product approved and launched, and certainly expand the utilization of axatilimab in a variety of indications. Earlier in the treatment course for GVHD, we're pursuing IPF. So that's -- these are -- this is a global partnership with Incyte and so it's gone quite well. And we continue to believe that it will expand and continue in flexibility in the way we envisioned it to start. So we're very happy with that.
This concludes the question-and-answer session. I'll now turn the floor over to Mr. Michael Metzger for any additional comments or closing remarks.
Thank you all. We appreciate you all tuning in today to discuss the progress we have made and the exciting milestones ahead for the company. We look forward to seeing you at our planned investor events, including the upcoming [ BTIG ] conference in August. And with that, we wish you a good day. Thank you so much.