Syndax Pharmaceuticals, Inc. (SNDX) Earnings Call Transcript & Summary

Good day everyone and welcome to the Syndax Revuforj FDA Approval 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.

Great. Thank you, operator. Welcome, and thank you all for joining us on this exciting day to discuss the FDA approval of Revuforj. I'm Sharon Klahre, and I'm joined on the call by 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 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 the forward-looking statements on Slide 2. Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation 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 15, 2024, only. A replay of this call will be available on the company's website, www.syndax.com, following its completion. And with that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Thank you, Sharon, and thanks to all of you for joining us today. Let's start with Slide 4. Today marks another major milestone for the leukemia community and everyone who has contributed to the development of revumenib, now known as Revuforj. We are thrilled that the FDA has approved Revuforj for the treatment of relapsed or refractory acute leukemia with a KMT2A translocation in adult and pediatric patients 1 year and older. With this approval, we have the privilege of delivering the first and only FDA-approved menin inhibitor. Underscoring the serious unmet need and potential for Revuforj to be a practice-changing therapy, the FDA previously granted revumenib Breakthrough Therapy, Fast Track and Orphan Drug Designations as well as Priority Review. The new drug application or NDA for Revuforj was reviewed under the FDA's Real-Time Oncology Review program, or RTOR, which enables extensive engagement with the agency. We are very grateful to the FDA for their support and close collaboration throughout the review process and believe that we have established a strong foundation that we can continue to build on with future filings. With the FDA approval in hand, we look forward to launching Revuforj in the U.S. this month. As part of our prelaunch preparations, we hired a highly experienced and motivated customer-facing team that is ready to hit the ground running with Revuforj. We have already completed extensive customer profiling work that we believe will pave the way for a successful launch and enable us to firmly secure the advantages of being first to market with this important new class of therapy. Later in the call, Steve will provide more details on our U.S. launch plans. Now turning to Slide 5. I want to briefly review the urgent unmet need that drives our team to deliver for patients and clinicians. Rearrangements of the KMT2A gene causes approximately 10% of acute leukemias and are associated with a very poor prognosis and high rates of relapse. A cancer diagnosis is terrible at any age, but KMT2A rearranged acute leukemia is an especially devastating disease because it primarily affects younger adults and children. As you will recall, the median age in our AUGMENT-101 trial was approximately 35. Historically, only 5% of these patients achieved complete remission after 3 or more lines of therapy. And the median overall survival is less than 2.5 months. For the first time, relapsed or refractory acute leukemia patients with a KMT2A translocation will have an FDA-approved targeted therapy available to them. This is a major breakthrough that we are very proud to deliver. Before I turn it over to Neil, I want to take a moment to extend my heartfelt gratitude to the entire Syndax team for their hard work and unwavering dedication to patients. I'm also deeply grateful for the contributions of the patients, their families, clinicians and study sites who participated in our trial as well as the many others who have supported our important work. And with that, I'd like to ask Neil to provide an overview of the Revuforj label and our Revuforj clinical development program. Neil?

Thank you, Michael. It's a pleasure to be on the call with you all today and to be part of bringing this much needed new medicine to patients fighting a very aggressive and difficult-to-treat form of acute leukemia. Starting with Slide 7, I'd like to provide a brief overview of the Revuforj label. Revuforj is indicated for the treatment of relapsed or refractory acute leukemia with a KMT2A translocation in adult and pediatric patients 1 year and older. Revuforj is an oral medicine that was approved in 3 different tablet strengths: 25 milligrams, 110 milligrams and 160 milligrams. The recommended dosage is adjusted based on patient weight, above or below 40 kilograms, and use of concomitant medications that strongly inhibit the function of CYP3A4 enzymes. The label recommends that Revuforj is taken for a minimum of 6 months to allow time for a clinical response. For patients who are unable to swallow tablets, the instructions for use describe how the tablets can be crushed and dispersed in water. We expect the 110 and 160-milligram tablets to be available for order in the U.S. through a network of specialty distributors and specialty pharmacies this month. The 25-milligram tablets, which may be used to treat patients who weigh less than 40 kilograms, are expected to be commercially available in the late first quarter or early second quarter of 2025. Prior to the commercial availability of the 25-milligram tablets, an oral solution of revumenib will be available through an expanded access program to allow for dosage of patients who weigh less than 40 kilograms. On Slide 8, I'd like to briefly review the design of AUGMENT-101, the Phase I/II multicenter trial, that formed the basis of the Revuforj approval. AUGMENT-101 was designed to evaluate revumenib as a monotherapy in a broad range of patients, including adults and children with relapsed or refractory AML, ALL, MPAL with KMT2A rearrangements. In Phase II, the primary efficacy assessment was based on the rate of complete remission, or CR, plus CR with partial hematologic recovery, or CRh. Notably, during the FDA's review, the agency decided to include in their efficacy evaluation data from Phase I and Phase II patients with at least 5% blasts at baseline and a KMT2A translocation by local assay who are dosed at the recommended Phase II dose and completed 6 months of follow-up or responded or discontinued early. Utilizing these criteria, the efficacy population increased to 104 patients. On Slide 9, you can see the baseline demographics and disease characteristics of these patients in the efficacy population. As you would expect, this is a relatively young population with a median age of 37. The youngest patient was 1 year of age. 83% had AML, 15% had ALL, and 2% had MPAL. This was an advanced heavily pretreated population. 59% of patients had failed to respond to their most recent salvage therapy, and 21% did not respond to their initial treatment. The median number of prior therapies was 2 with a range from 1 to 11. 44% underwent prior stem cell transplantation. On Slide 10, you can see a summary of the results in the 104-patient efficacy population in the label. The rate of CR plus CRh was 21%, the 95% confidence interval ranging from 14% to 30%. The median duration of CR plus CRh was 6.4 months at the time of the data cutoff. The upper bound of the 95% confidence interval had not been reached. The median time to CR/CRh was 1.9 months. 24 of 104 patients or 23% underwent stem cell transplant following treatment with Revuforj. This is notable given that stem cell transplantation is the only potentially curative option currently available for these patients. Historically, less than 5% proceed to transplant. As we expected, the efficacy data in the label are highly consistent with other data sets that we have shared previously. Further, the results are remarkable compared to what has been observed historically for these patients. We know from our extensive interactions with key opinion leaders that clinicians are excited to have Revuforj as a new treatment for appropriate patients. On Slide 11, you can see an overview of the safety information on the label. The safety evaluation was based on an FDA analysis of 135 patients with relapsed/refractory acute leukemia with KMT2A translocation who were treated with Revuforj. Similar to other targeted therapies for AML that induced differentiation of leukemia cells into normal hematopoietic cells, the Revuforj label includes a box warning for differentiation syndrome or DS. DS was Grade 3 or 4 in 13% of patients. There was one Grade 5 DS according to adjudication by the FDA. Treatment interruption due to DS of any grade was only required for 7% of patients, and treatment was withdrawn for only 1% of patients. With regard to QTc, 12% of patients experienced Grade 3 QTc prolongation. There were no Grade 4 or 5 events. Overall, only 5% of patients required dose reduction due to QTc prolongation. The most common adverse reactions listed in the label are consistent with our previously reported data. Overall, adverse reactions leading to dose reduction and permanent discontinuation were low at 10% and 12% of patients, respectively. Moving to Slide 13. As a reminder, results from the Phase II AUGMENT-101 interim analysis of 57 efficacy evaluable patients with relapsed or refractory acute leukemia with a KMT2A translocation were recently published in the Journal of Clinical Oncology. The publication provides further information on other endpoints from AUGMENT-101. 70% of CR or CRh responders in the interim analysis achieved MRD negativity. In addition, 39% of responding patients proceeded to transplant, with half of these resuming therapy following transplant. These data are compelling considering the very poor outcomes for these patients historically. To ensure that the prescribing community is aware of the clinical data supporting Revuforj, we have a robust publication and congress plan underway. And we'll continue to closely partner with many of the key opinion leaders who participated in the AUGMENT-101 trial and who have been instrumental in the development of Revuforj. We will also continue to engage with KOLs and the committees who play an important role in developing NCCN guidelines. To support prescribers, we have assembled a team of seasoned medical affairs professionals with extensive oncology experience who've already been in the field for some time exchanging scientific information with clinicians, including those at leading U.S. cancer centers. Turning to our development pipeline. We continue to advance the evaluation of Revuforj in several other key populations as shown on Slide 14, both as a monotherapy and in combination with other agents across a variety of settings, including frontline and post-transplant maintenance. Earlier this week, we reported positive top line pivotal data from patients with relapsed or refractory mutant NPM1 AML in our AUGMENT-101 trial, and we are on track to submit a supplemental NDA in the first half of 2025, building off today's approval. We also recently announced that there will be multiple presentations at ASH this year that will highlight the latest data available from several ongoing trials, including data from the SAVE trial in relapsed or refractory AML that demonstrate revumenib's potential combinability with venetoclax and oral decitabine. We are also looking forward this quarter to an anticipated update from Phase Ib AML trial of revumenib in combination with venetoclax and azacitidine in frontline patients as well as the anticipated initiation before year-end of our pivotal frontline trial with the triplet in AML patients unfit to receive intensive chemotherapy. With the approval of the first indication for Revuforj and our robust clinical development strategy that could support future label expansion, we believe that we have the potential to transform the standard of care in multiple areas of high unmet need. With that, I'll turn the call over to Steve to review our commercial readiness and launch plan for Revuforj in the U.S. Steve?

Thank you, Neil. For me and the commercial team, it is incredibly exciting and rewarding to have the opportunity to deliver a new medicine that has the potential to make such a profound impact for patients and their loved ones. Starting on Slide 16. Now before I dive into discussing the preparations we have made to support a robust launch, I want to take just a moment to discuss the reasons why we believe Revuforj is set up for both short- and long-term success. First, we're positioned to secure first-mover advantage in an exciting and emerging new therapeutic class. We believe that physicians' familiarity with Revuforj will expand quickly because the patients within our label have an urgent need for new treatment options. Second, our clinical development program has included both adult and pediatrics, which has allowed us to achieve a label that covers a broad patient population. Third, with promising clinical data across the absolute broadest population to date for menin inhibitor, we're excited about the ample opportunities we have to pursue future label expansion. And last, but of course, not least, we have a near-term opportunity for a very unique launch trajectory. With positive top line data in hand from patients with relapsed or refractory mutant NPM1 AML, we plan to submit a supplemental NDA filing in the first half of next year. And if approved, we'd be positioned to launch into a second indication within 12 months, leveraging our already established commercial organization and physicians' familiarity with Revuforj. Turning to Slide 17. In terms of the initial market opportunity, we estimate that there are about 2,000 patients in the United States that fall within our label, representing an estimated total addressable market of about $750 million. Now importantly, as Neil described, we've got a number of ongoing and planned trials that could allow us to expand the Revuforj label over time into the additional patient populations and blockbuster opportunities shown on the right side of the slide. Moving to Slide 18. Now that Revuforj is FDA approved, our team will focus on 3 launch imperatives to enable a successful launch and secure the advantages of being first to market. First, we'll dedicate ourselves to ensuring that absolutely no appropriate patient is left behind. Now given the acute nature of this disease, these patients require rapid identification and rapid treatment. Now to support this first imperative, we'll be leveraging advanced data and analytics to help us identify patients and activate targeted physician engagement. One important thing to note is that screening for KMT2A rearrangements is already a routine part of the genetic testing that patients undergo, enabling clinicians to efficiently identify appropriate patients for Revuforj. Our second imperative is to engage and support all key stakeholders who are involved in the diagnosis as well as the treatment of these patients. Now in a few moments, I'll share more about the purpose-built organization that we've established to support this initiative. And our third imperative is to deliver a premium, best-in-class experience for patients and clinicians. We recognize that these are absolutely critically ill patients that need rapid access without major barriers. To deliver a positive experience for patients and prescribers, we have established a limited distribution model with 2 industry-leading specialty pharmacies, Onco360 and Biologics, as well as a network of specialty distributors. These specialty pharmacies are well recognized for their ability to help patients and prescribers efficiently navigate the process of obtaining access to critical oncology medicines, particularly in their launch phase. And their partnership will supplement the support that we will provide directly through our own dedicated patient support program that I'll talk about shortly. Turning to Slide 19. Now to deliver on our strategic imperatives, we've assembled a highly experienced and talented customer-facing team that will engage and support the various stakeholders involved in the patient treatment journey. While it will, of course, be key for us to engage with hem/oncs, we have established different multidisciplinary roles within our commercial and medical affairs organizations so we can also effectively support all the other key stakeholders at each institution, too. This includes pathologists, nurses, reimbursement specialists, purchasing administrators and more. To support Revuforj and Niktimvo into the future, we've built an exceptional team of approximately 50 customer-facing professionals with an average of 22 years of experience, primarily in hematology/oncology, also with an average of 6 product launches per representative and importantly, strong and profound pre-existing relationships with key clinicians and institutions. Moving to Slide 20. Our field teams will target the approximately 2,000 accounts in the U.S. where more than 98% of patients with KMT2A rearrangements are expected to receive treatment, with our highest focus dedicated to the highest volume centers of excellence. We estimate that roughly 200 accounts or about 10% of our target accounts represent more than 2/3 of the patient opportunity, making this a very manageable effort for our team to execute on. Our field teams have already made tremendous progress preparing for a successful launch. Prior to the approval, they have already been in the field engaging with our 2,000 target accounts, including the largest and most influential academic centers in the country. They've been driving awareness of Syndax as well as the mechanism of disease and profiling accounts to understand the patient journey and treatment workflows. Within short order, our field force will be fully trained on the label and laser-focused on providing key decision-makers with product information and support. Turning to the payer front in Slide 21. Because KMT2A rearranged acute leukemias tend to skew towards a younger patient population, we estimate that most patients will have commercial coverage, and a smaller percentage will have Medicare Part D or Medicaid. Our seasoned market access and medical affairs teams have already done extensive work educating payers on the burden of disease and providing scientific information about our program. Prior to the approval, we have reached plans covering more than 90% of all managed care lives. Payers have told us that they recognize the urgent unmet need in this disease, and we anticipate that they will be prepared to make timely evidence-based decisions now that the product is approved with formulary approval expected to build over time. While Revuforj is being reviewed for formulary inclusion, we expect it will be covered for reimbursement through the medical exception process, an approach that cancer centers and our pharmacy partners are very familiar with navigating for new oncology medicines. Now with regards to pricing, a 30-day supply of the 110 and 160-milligram tablets, which consist of 2 bottles, will have a wholesale acquisition cost or a WAC of $39,500. Our pricing reflects the value of Revuforj and is anticipated to support broad payer coverage based on the robust research that we've done to date with payers. Like other differentiated first-in-class oncology therapies, we anticipate minimal rebating with Revuforj. Moving to Slide 22. To ensure we're providing patients and their caregivers with robust support, we're pleased to have our own dedicated patient support program that will supplement the assistance provided by our specialty pharmacy partners. Our SyndAccess patient support program will provide a level of support that is on par with the programs offered by industry leaders in oncology. SyndAccess will provide patients and caregivers with assistance navigating the insurance process and will provide financial assistance or co-pay support to eligible patients. We also have dedicated oncology certified nurses who can answer questions about the product and provide ongoing personalized patient support, which is anticipated to optimize medication adherence. In summary, we are very well prepared and very excited to launch Revuforj. We're confident that we can deliver outstanding service that makes a meaningful difference for critically ill patients and establishes Syndax as a trusted partner for health care providers. I'll now hand the call over to Keith to provide a few comments on financial considerations.

Thank you, Steve. We are in a strong financial position to launch our first 2 medicines while continuing to fuel the advancement of our pipeline. Our pro forma cash balance at the end of the third quarter approached $750 million, and we expect that to fund the company through profitability. Over the coming quarters, we look forward to providing you with updates on the progress of both launches. While product data feeds will be shielded, we will report net Revuforj revenues as well as our 50% collaboration profit split with Incyte on sales of Niktimvo. Additionally, we'll endeavor to provide other meaningful commercial and financial metrics that provide further insight into the trajectories of both launches. With that, I'll now hand the call back over to Michael.

Great. Thank you, Keith. Now turning to Slide 23. This has been a tremendous year for Syndax, characterized by historic accomplishments and strong execution from everyone on our team. Revuforj is our second novel medicine to receive FDA approval this year following the approval of Niktimvo in chronic graft-versus-host disease. The FDA approval of 2 first-in-class medicines in 1 year is an absolutely remarkable achievement for a biotech company of our size and reflects the skill and dedication of our entire organization and network of collaborators. The road ahead is just as exciting with multiple near-term value-generating milestones on the horizon, as you can see on this slide. We look forward to continuing to leverage our expertise and momentum to advance our mission and build additional value. And with that, I would like to open the call for questions. Operator?

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

Congratulations on the approval. I'm just wondering, what are the gating factors to getting those 25 mg tablets for the sort of lower-weight younger patients? And assuming that -- and should we assume parity pricing there? And then second question is on the label negotiations, did FDA consider sort of differentiation syndrome as sort of a revumenib-specific AE? Or was it considered more of a class consideration for menin inhibitors?

Thank you, Anupam. Appreciate the questions. So maybe I'll take the first one and then hand the second question over to Steve. I think the gating issue for 25 milligrams is it's approved in the label, as you see. We have a little bit more CMC work to do, should be able to get it out to providers very soon first quarter -- end of first quarter, beginning of second quarter. So it's just a little bit more work on the supply there. But as I said, it's approved in the label. And then you had a second part to the first question. Remind me what that was, Anupam.

Parity pricing for that tablet.

Right. Steve, do you want to mention...

Yes. Well, we're not going to share the pricing yet on the 25 mg. As it comes closer to launch, we'll share that information.

And then, Anupam, on the -- on how the FDA looks at differentiation syndrome, this is our review, so we're not generally commenting on other reviews or they weren't necessarily commenting on other reviews that they've done relative to our label and our approval. What's, I think, factual is that there -- I think for the last 6 years or so, all of the targeted therapies within AML have received a black box for differentiation syndrome. So they have a heightened awareness for differentiation syndrome. And so we had expected -- long expected that this would be the case, that we would receive a black box for differentiation syndrome. So whether they -- whether you could call that class related, I think our expectation is that all of the menin inhibitors will be -- will receive a black box at least for differentiation syndrome.

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

Congrats on the second in 1 year. Looking at the label language, which seems to describe at least the proportion of patients that move to transplant, how do you see the ability to speak to physicians about post-transplant maintenance? And second, if you apply the same FDA analysis criteria to the NPM1 population from Phase I, what number meet the criteria and could be included in an sNDA review? And how many of those had a CR/CRh? I think everyone will be thinking about is the NPM1 data and if they will stay consistent and above the approval benchmark. Congrats again.

Yes. Thanks, Brad. Appreciate the question. So maybe in terms of Brad's first question, Steve, do you want to take that?

Yes. I'd just say, Brad, in terms of the label, we feel pretty good. We feel very good about the data that's in there. And I wouldn't use the label as the only indicator of what we can say in promotion. We think we gave physicians a good picture of what was in the studies and then ultimately, what happened in the conduct of the trial. I think the specific question was around post-transplant maintenance. Obviously, the drug doesn't have an indication for that. But as we know, physicians have a bias for treating and it's often putting patients back on the drug that got them to transplant. So we expect that they'll be able to go to medical information for more information on the use, and they'll follow typical practice patterns that they have with other agents.

And Brad, your second question was a somewhat complicated one, but I'll answer it to the best of my ability. So I think you're referring to the analysis that the FDA did on this population. So interestingly, the FDA did their own analysis that was outside of the prespecified analysis for approval here. And they included patients that were in the Phase I trial for -- of AUGMENT-101. So this was not just the pivotal trial Phase II, but it also included patients from Phase I. So they did their own analysis and essentially increased the number of patients to be analyzed here, which, of course, as you related, and I think you're relating to the NPM1 pivotal trial that was just reported out the top line data, we do have a difference in size between the efficacy population and the safety population. It's 64 patients in the NPM1 efficacy, 84 in the safety. And one question is, of course, whether the agency would look at additional patients for efficacy at some point. I don't think they have a -- they define the trial and the conduct of the trial and the SAP and the statistics based on agreement prior to starting that trial. So we've had agreement with the agency on both KMT2A design as well as the NPM1. And so that is something that are always at their -- once you provide them the data, they can always do their own analysis. So the NPM1 population, they'll do their own analysis, assuming that the filing is appropriate for that. And then, of course, we have Phase I data that we also conducted for NPM1. They'll see all this data in a filing from us, hopefully, in the first half of next year. That's the plan. So I don't have a really concise answer for you. All I'm -- what I guess I'm getting at is that the FDA ultimately runs their own analysis on the data that's provided, and they'll either approve your drug or they won't. But we feel very confident, the data that we've provided so far, as it was for KMT2A, and NPM1 will be, we believe, approvable.

Our next question comes from Peter Lawson with Barclays.

Thanks for the update. Congratulations on the approval. You mentioned about the supplemental NDA for NPM1. Will you also pursue the NCCN guideline updates as well?

Right. So thank you, Peter. For the sNDA or are you talking about KMT2A?

For the sNDA.

Right. So first step, of course, to get the drug approved, we'll need to get the results published -- the NPM1 results published in a journal, and that's our plan to do that in short order. And then we will be submitting them, yes, for guidelines thereafter. So we are -- we have a very, I'd say, accelerated plan to accomplish all of that.

Okay. Okay. And then your expectations around the duration of therapy in the real-world setting. How do you think that could change for the third line versus second-line patients?

So thanks, Peter. I think -- look, the duration of therapy that will play out in the real world, I think we've seen data, the KMT2A data, as you saw the update for ASH, the 57 patients that were in the efficacy evaluable population that are in the label, those were followed for an additional 7 months. And with the result of transplant and patients staying on therapy, that median went out to 13 months. So I think there's -- obviously, it's an ongoing story and how long patients can stay on therapy and how long the duration of response will ultimately be. I do think treating earlier in the course of the patient's journey, second line versus third line could make a major impact on how long patients can stay on therapy versus more patients will likely go to transplant, and then potentially go back on therapy thereafter, which could really extend duration of response in therapy. So to be seen, but I think it's a very positive set of facts that we'll have to see how it plays out in the real world.

Our next question comes from the line of Chris Shibutani with Goldman Sachs.

This is Kevin on for Chris, and I wanted to add our congratulations. Just a quick one around ASH for NPM1. Can you talk about what you may be able to show there in terms of additional analyses and what we should expect? And then for the actual data at the conference, the SAVE data in the abstract, I believe the cutoff was July. What should we expect in terms of differences between the abstract and the actual data?

Yes, Kevin, thank you so much. Really appreciate it. So your 2 questions. So the first one relates to ASH and what we're likely to see in terms of additional analyses around the NPM1 data that we just presented. We haven't been so precise about what we'll have there, but I do think that there are some key questions we would hope to answer with additional data, specifically breaking out treatment and response before venetoclax. As you know, the patient population was heavily pretreated with venetoclax, 75% of the patients received it before going on our trial. So I think we would want to see what the response rate looks like before they -- for some of the patients who took our drug before having venetoclax. So that's important. Other things like mutational analysis and breaking that out and we'll be able to look at some follow-up on patients that we didn't have at the time of [ top line ] results. So there'll be a number of important data that I think will be helpful to people so they can understand it in more depth. And then in terms of the SAVE data, not really at liberty to say much about what to expect there. The last update was -- or last update last year at ASH was in 9 patients. The ASH abstract issued last week indicated 26 patients. There may be additional data that comes out at the meeting, and that's Ghayas Issa’s trial at MD Anderson. We're excited to see those data. They were quite robust and really indicated high rates of response and patients doing quite well, staying on drug and so forth. So hopefully, that will be added to. I can't give you any more than that at this point because, frankly, we haven't seen that data.

The next question is from Kelly Shi with Jefferies.

Congrats on the approval. So I have 2. Firstly, is the KMT2A molecular testing conducted separately or along with other AML biomarkers? So specifically, if physicians wish to use off-label in NPM1 patients, is the patient genetic information available? And I also have a follow-up.

Neil, do you think that -- is that something you can?

I'm not sure I understood the question, I'm afraid. Could you repeat the question first?

So basically, the KMT2A molecular testing and NPM1, like -- conducted on like altogether, so you have the information available or like if physicians wish to use off-label in NPM1 patients, is the patient [ genetic ] information available?

Yes, thank you for clarifying your question. So patients are routinely screened for both mutations, right? So they are part of panels that are -- they also include other mutations such as FLT3, IDH, et cetera. So NPM1 and KMT2A rearrangements are routinely tested for. So the genotype of the tumor will be known. Of course, the current approval only relates to KMT2A rearrangements, but patients are also tested for NPM1 mutations as well.

Okay. I also have a quick one. So 50% of the patients resumed Revuforj treatment post the transplant. Curious how long the patients actually stay on the treatment?

Right. Thank you, Kelly. I think we'll have more of that. Are we talking about -- you're asking about NPM1? Are you talking about KMT2A?

KMT2A.

Right. So we'll see. I mean we've data. We will see how patients have done. Last year, we presented data at ASH, and we'll have additional data at the meeting this year. We're presenting, as you know, updated data set from the pivotal where we look at instead of 57 patients, we followed those patients for longer. We've also -- efficacy data set is 94 and the safety is 116. So we'll look at the subset of patients who went to transplant and how they performed thereafter. So we just haven't presented that data yet.

The next question comes from Phil Nadeau with TD Cowen.

Congratulations on the approval. Great news. So I guess, first, on the QTc labeling, it looks like the label is requiring monitoring once weekly for the first 4 weeks and at least monthly thereafter. Is that standard QT monitoring? How much of a burden will that be on the physicians and patients?

Great. Thank you, Phil. Really appreciate it. I'm going to turn it over to Neil to answer that.

Thanks, Phil. Yes, it is pretty standard. We've actually talked to a lot of KOLs about this, and we have -- some of us have experience with -- from other scenarios. And we don't believe that this is a burden at all, and that's certainly the feedback that we're getting from our KOLs. These patients are in the clinic frequently. So the fact that they might have to occasionally have an EKG is not a substantial burden. In fact, you heard a little bit of that from Eytan Stein if you're listening to Monday's call. So we don't -- or more importantly, the investigators and the physicians don't really see this as burdensome at all.

Great. That's helpful. Then second, a follow-up question on the data that's in the label. So it sounds like the 104 or so patients in the FDA's analysis, somewhat of a different population than the 97 patients that were in the ASH abstract. Will you ever be able to publish or present the data set that the FDA itself analyzed for the label? Is that something that you'd have access to that you could either release at ASH next month or at any point, put in a publication?

Thanks Phil. Neil, do you want to take the follow-up?

Yes. Well, actually, we're updating a broader analysis at ASH, which isn't the same as the FDA's analysis. And the fact is that the FDA run that -- so you guys know the procedure. So we do the analysis. We have our own programs. We provide the data sets to the FDA. They run their own analysis. So it's in the label, as you pointed out. So that's what the FDA did. It's a little difficult for us to actually replicate it because it's not like they send us back over their program. So what we're seeing in the data, and we don't know that, that will be helpful because what we're seeing in the data is highly consistent with what we've always reported both in terms of efficacy and safety. So I'm not sure it's something that we would necessarily want to do or even could do, to be perfectly honest.

Yes. I think I'd just add, Phil, I don't think we have any plans to do that, but it's a good question.

Great. Last question is for Keith. Keith, I think you said that the scripts from the 2 specialty distributors are going to be blocked, so we're not going to be able to monitor them through our typical services, is that right?

Yes, that is correct.

Congrats again.

The next question is from Michael Schmidt with Guggenheim.

Congrats on the approval from us as well. Maybe just a follow-up. So regarding the NPM1 data that was just released earlier this week. So how does the FDA label that you have received now for KMT2A and perhaps the overall FDA interactions how does that perhaps impact your confidence in the NPM1 approval and label? And if you were to do a similar analysis, a similar [ pool ] analysis, including Phase I data, would that meaningfully change the CR/CRh rate for the NPM1 cohort?

Yes. Thanks, Michael. I think you're getting at a similar question to what Brad had earlier. So look, I think the approval here is a fantastic achievement related, of course, to the KMT2A data, but there's a lot of shared information that relates to -- that will go into an NDA package that is relatable to NPM1 as well. But it definitely -- I would say, having an approved drug, in a related area is very good for our NPM1 -- potential NPM1 approval. So we have very good interactions with the agency. It's been successful, and we expect that we'll be successful with the NPM1 filing as well. So our confidence is high. The analysis that the FDA did was not in accordance with our SAP, right? So they had included Phase I and Phase II patients, right, at the recommended Phase II dose, which was 163 milligrams BID, and that was done before certain data cutoff in July of '23. So I think the corollary here that you're looking for is that could the agency take a look at our expanded safety database, could they look at patients in the Phase I that were dosed at the RP2D they could. Our expectation and in accordance with our SAP was to generate the results that we presented this week. And we expect those are robust and sufficient for approval. Ultimately, they'll go through review. And yet the FDA can, in fact, look at those data from Phase I. And I'll remind you, Phase I data for NPM1 at a CR/CRh that in the patients, it's 14 patients had a CR/CRh of 36% and all very consistent with overall response rate, about 50% and good duration of response. So I think the data that we generated there is highly consistent with what we have generated this week. And then, of course, we haven't looked at the data in the expanded safety population, but we expect it to be representative and very, very similar to what we presented already. So to us, it's all very supportive of approval, and we expect that we'll have a successful filing when it comes time.

Right. Makes sense. And then just a commercial question as we think about sort of the first commercial quarters for revumenib. I think you mentioned it's obviously unlikely to see a patient bolus just given the short nature of progression or survival essentially. But as we think about the launch, are there any items that we should consider around inventory in stocking or other factors as we try to model kind of the launch in the first few quarters?

Steve, do you want to take the first part on maybe the bolus question? Maybe, Keith, you could chime in a little bit on the numbers.

Yes. No, happy to. And Michael, good question. I think when we think about the launch, I think everything is in place for what I would call a very strong launch. We're certainly ready. But when you think about factors in this market and when we look at uptake, there is high unmet need. There's no doubt about it. We've talked on this call. We've talked on previous calls. Patients are at risk with a poor prognosis. There's nothing to treat. They're not waiting around, of course. So there's really no bolus, but there are patients out there. Second point I'd make is that patients are readily identified. We talked about testing procedures on this call. Every treatment center does it. They may do it differently, but they all do it, so they know who the patients are. And I'd say the third piece is just our readiness. We're already connected to treatment centers. We've had customer-facing folks in market for the last few months, profiling accounts, understanding how they test, understanding how they treat patient journey, how they distribute. So the patients are out there, I think, we'll find them. And I think based on those things, this will translate to really immediate traction in the marketplace.

Yes. And Michael, on the second part of your question, as Steve mentioned in his prepared comments that we're using just 2 specialty pharmacies and a small limited distribution network of other specialty distributors. So because of that limited distribution network, we don't expect there to be a lot of inventory in the channel at any time.

Congrats on the early news here this Friday.

The next question is from Yigal Nochomovitz with Citi.

Congrats again on the very early approval. I had a question on Slide 17. I'm just curious with respect to the range that you cite for the NPM1 population, 3,000 to 4,500. Is there a reason that you have less precision on that versus the other populations that you're describing?

Yes. Thanks for the question. Maybe I'll ask Anjali to address that question.

Yes. Sorry. So -- and you mean the confidence interval, I didn't -- I'm sorry if I didn't fully appreciate, Yigal, the range.

I think he's referring to...

Just the range.

Yes, they're referring to the number of patients. I think we have -- was it 3,000 to 4,500 on the market slide, Anjali.

Yes. Sorry. Okay. Thank you. Thank you for explaining that. So Yigal, we have to think about the different ways that an NPM1 patient would get to relapsed/refractory. I think with KMT2A, there is a more defined population of patients that are fit just based on the age of that population. And so -- and we know that 10% of patients with KMT2A have -- sorry, with AML have a KMT2A rearrangement as well as with ALL. And so we can trace their journey a little bit more definitively for NPM1. There's a little bit more of a variability between what percentage are fit versus unfit. I've seen from 45% to 60% can be fit, and that gives you a range. And then the proportion that will relapse also depends on whether they fall into the fit or unfit category because the fit population has a small percentage that can be cured. So the range does get a little bit bigger. I think there's also a broader range of estimates for what percent of AML is NPM1, and that has ranged from 28% to 36%. So it just expands the population. I think one thing we have been hearing from physicians also is that since this is the first robust data set in a relapsed/refractory NPM1 population, there is potential that they think about a menin inhibitor as a second-line agent. There aren't many other data sets that have been published in this population and you've got an easy to -- an oral, easy to tolerate, effective medication that can be well managed with their patients, and that may be something that physicians start to reach to earlier, which could expand the population to closer to 5,000. So hopefully, that helps address your question.

Yes. No, that definitely helps. And it was sort of commented with respect to my second question, which is, as you pointed out, it was 28% to 36%. I was under the impression that it's about 3x, as you say, NPM1 to KMT2. But this range suggests that a little lower than that. Is that a revised assessment? Or are you guys just being conservative? Can you just clarify that part?

Yes. For NPM1, I think that range does suggest 2.5 to 3x the population for KMT2A in the front line. But when you get to the relapsed/refractory population, as I mentioned, there are a proportion of the fit NPM1 patients that need nothing beyond 7 plus 3, and they don't come back into the fold, whereas with KMT2A, there is a much higher proportion that will relapse. So when you get to the relapsed/refractory setting, the ratio between these 2 come closer a little bit. So that's -- maybe that's also what would explain the differences.

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

Congrats on the approval today. Maybe one question, sort of a follow-up from the earlier one for the duration of exposure. The label notes a median duration of exposure of 2.3 months. I guess, is there a considerable difference between the median versus the mean duration of response? Any color would be useful for modeling purposes as I think previously, we were looking at a 9-month number.

Yes. Anjali, do you want to take that question as well?

Yes. So for KMT2A, we were thinking about the 9 month, and I can go into the details if that's helpful, but it was based on the distribution of patients because such a high percentage were going to transplant that really extends the length of duration because we're hearing from physicians such a significant proportion of patients can go back on therapy posttransplant. I think in the NPM1 population, it's more focused on the patients that are responders versus nonresponders. And it does seem to be an upside of going to transplant, but not as robust or significant as we saw in the KMT2A population. So what we saw was patients staying in response -- a CR/CRh response in NPM1 population close to 5 months, we're also seeing -- and I think we highlighted in the label, it was 2 months in KMT2A to get to that response. I think in NPM1 being an older population and then having a significant prior [indiscernible] and prior therapies may have impacted the time it takes to get to CR/CRh. So we estimate the responders could be on therapy a median of 8 months and then the nonresponders similar to KMT2A about 3 months. So the -- when you -- and it was about a 50-50 response rate for responders, nonresponders. So that gets you to about 6 cycles for NPM1 and because of the transplant, about 9 cycles with KMT2A. That's what we believe today based on the data. But I do think, as I was alluding to in the prior question, with NPM1, just like with KMT2A, this is the first time we've got strong evidence of efficacy for an agent in either of these populations. And instead of it being a median third line or fourth line agent, we think it's going to get utilized in earlier lines, and that could provide significant upside on those numbers.

Congrats again.

Our next question is from the line of Justin Zelin with BTIG.

Congrats on the approval, guys. Great news. Maybe just a follow-up on the last question. I just want to make sure I heard it right. Anjali, you said 9 months expected duration of treatment for KMT2A and 6 months for NPM1. Just want to make sure I heard that correctly.

Yes, median. Based on the current later-line data set, and then we think in both cases, there's potential for extension because as you see across oncology, as you treat earlier, you get more patients to respond and you can keep them on therapy longer. We may even be able to get more patients into transplant in the second line because they're fit -- more fit and potentially respond better to therapy as well. So that would also expand in both populations the potential duration, because we do see even in the NPM1 population physicians wanting to put their patients back on therapy posttransplant.

Understood. And maybe a question for Steve. Just your expectation on the breakdown of patients getting treated at academic centers versus the community and just how knowledgeable the community docs are about treating differentiation syndrome or monitoring for QTc?

Yes. Good question, Justin. I'd say this, like most targeted therapies in the space, I mean, the majority of the business is going to be in academic centers. That's where the centers of excellence are. And so that's typical. We expect the same with Revuforj. We have the entire market covered. I think I mentioned in my prepared comments, we've got about 50 representatives on the ground. We'll call on 2,000 accounts. I mean 80% of the business will be in academic centers, but community oncology is growing, particularly in certain parts of the country. They're smart. They'll take the cue from the academic centers. I think initially, what I'd expect is that patients in the community setting will go to academic and then we'll come back. So it's important that we cover both. But I think over time, it will evolve. I think ultimately, you'll see 80% academic and 20% community, but that will evolve over the coming years.

The next question is from Salim Syed with Mizuho.

Congrats on the approval. Just a few from us on the ECG and QTc discussion here. So, I guess, number one, is it expected here that the ECGs will be covered by payers? And how much of that -- what should be the expected price for these ECGs that the payers would have to bear? And was this taken into account as you price the product out? That's the first question. And then I have a couple of follow-ups.

Yes. Thanks, Salim. So EKGs are very -- it's a simple machine and it's in the office. These are pretty cost-effective, very short tests that they run routinely within their office setting. So these are not expected to be costly. I don't think it's a reimbursement issue. I think it's very well managed within the health care system. So again, remember, these are leukemia patients. So they get all sorts of tests, including EKGs on a regular basis. So I don't think this really factors into the cost overall of how we thought about Revuforj. So that shouldn't be a barrier.

Okay. And is it your general expectation that the QTc language will apply to all menin inhibitors for other labels? Or is this something that you -- at this point, you believe would pertain only to your product?

Yes. Thanks for the follow-up. Well, we'll have to see what other products are -- what comes with their data and what they present to the agency. All I can tell you at this point is that we have some warning related to that because we've shown some QTc in our data. And so that's been expected that we would have -- you get called out and then you have certain procedures you have to be put in place to monitor it for QTc. But it's -- as you see, it's not a black box warning, and it's been very -- it's been identifiable, manageable and we use -- if it's Grade 3, we dose reduce and ultimately, the patients can stay on therapy and not discontinue. We've seen that in our trial. So very manageable side effect that, of course, I think, is adequately reflected in the label.

Okay. And just lastly, if KORA were not to get the QTc language in the warning section of their label, would you view this at all as a commercial disadvantage?

Steve, do you want to answer that question? Yes, sure.

Yes. I think the short answer is no. I mean I think what we've learned from physicians over time, all KOLs, I mean, they'll look at a full package on the drug. So it's never one thing that will drive their view and utility of 1 agent. We've tested a warning around QT for quite some time within market research, even the question on the payers, we've been full view, and it hasn't impacted the preference share that we see in our demand models when we're generating our forecast. So I think the short answer is we do not believe it would be a competitive disadvantage.

Yes. And I think just a follow-up. I think we obviously have the Eytan Stein, the thought leader on our call on Tuesday when we're talking about our data. I think when asked about QT, I think his response was that they're all -- all the physicians are aware of QT. A lot of different drugs have QT liability. This one doesn't factor into his choice one bit. And I don't think it -- whether you have another drug on the market that has -- doesn't have it. There's always -- there's a confluence of factors you take into account, as Steve said, to make your choice and having something like this is not a factor.

This concludes our question-and-answer session. I will now turn the floor over to Mr. Michael Metzger for any additional comments or closing remarks.

Great. Thank you, operator, and thank you all for joining us today to discuss this exciting milestone for patients, clinicians and for Syndax. We appreciate your continued support and really look forward to connecting with many of you again soon at our upcoming investor conferences and our ASH investor event. With that, have a great evening. Thank you.