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spk09: Good day, everyone, and welcome to the Syndax second quarter 2024 earnings conference call. Today's call is being recorded. All participants have been placed in a listen-only mode. You will have an opportunity to ask questions after today's presentation. If you would like to ask a question, please press star five on your telephone keypad to be placed into the queue. You may also press star five again to remove yourself from the queue. At this time, I would like to turn the call over to Sharon Clary, head of investor relations at Syndax Pharmaceuticals.
spk01: 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 Clary, and with me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer, Dr. Neil Gallagher, President and Head of R&D, Steve Kloster, Chief Commercial Officer, and Keith Goldanz, Chief Financial Officer. Also joining us on the call today for the question and answer session are Dr. Peter Oredemlik, Chief Scientific Officer, and Dr. Anjali Ganguly, 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 two. 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 statement as a result of various important factors, including those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, August 1, 2024 only. A replay of this call will be available on the company's website, www.syndex.com, following its completion. With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndex.
spk05: Thank you, Sharon. Good afternoon, everyone, and thank you for joining us today. Starting with slide three, this is a very exciting year for Syndex as we stand on the cusp of becoming a commercial stage company with the anticipated upcoming FDA approvals of Revimentib and Axotilamab, two first-in-class treatments for diseases with high unmet medical needs. 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 Revimentib combination data from the BEAT-AML and Augment-102 trials at the European Hematology Association, or EHA, Congress. These data, which Neil will review shortly, continues to support revumens potential to enhance current standard of care agents. At EHA, we also presented additional positive data from the Agave 201 pivotal trial, evaluating axotilumab 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, skin and joints, and sclerotic skin. Looking ahead, we are on track for a historic year with the anticipated FDA approval of Revimenib and Axotilmab coming soon. With axotilamab, 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 revimenib, our menin inhibitor being reviewed by the FDA for patients with relapse or refractory KMT2A-rearranged acute leukemias, we have a PDUFA action date of December 26, 2024. As we announced earlier this week, The FDA recently extended the PDUFA action date for Revimenib NDA from September 26 to December 26, 2024, a standard three-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 supports approval and continues to demonstrate the meaningful benefit Revimenib 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 Revumentib with strength as soon as we receive the anticipated approval. Later in the call, Steve will provide some additional color on our preparations for these two anticipated launches. We also have several other meaningful milestones approaching, such as the anticipated readout of pivotal top-line Revumentib data in relapsed or 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 Revimentib and Axotilamab 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 utility 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 will now ask Neal to review some of our recent data presentations and pipeline. Neal?
spk15: Thanks, Michael. Turning to slide four in Reviumenib, we have a robust clinical development strategy underway that will support the use of Reviumenib in KMT2A-rearranged and recent TM1 acute leukemias across the treatment paradigm. The development plan extends beyond the initial relapsed or refractory indication, with trials of Reviumenib in combination with standards of care that potentially support use in the frontline relapsed or refractory and post-transplant maintenance settings. On the next two slides, I will briefly review the data recently presented at EHA from the two combination trials that you see listed, BEAT-AML and Augment-102. On slide five, at EHA in June, we and our collaborators at the Leukemia and Lymphoma Society presented updated data from the BEAT-AML trial of Revimaniv in combination with venetoclax nasocytogenes, or Veneza, in patients newly diagnosed with mutant NPM1 or K22A-rearranged AML. This updated data set was a cutoff of the 1st of May 2024 and includes 24 efficacy-evaluable patients. 96% of patients had a composite complete response for CRC, and 92% had no residual disease and were therefore MRD-negative. As an older combination trial has conducted so far, two doses of Revimenib are being investigated, 113 milligrams and 163 milligrams administered every 12 hours. The dose-limiting toxicity, or DLT, window for each was cleared last year on this trial, and both cohorts are currently being expanded in order to identify the dose for 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 Revlimidib and Venaza observed in the study are consistent with data for Venaza from historical controls. For example, the addition of Revimenib to the doublet does not appear to exacerbate the myelosuppression associated with venasolone. Additionally, the BEAT AML investigators concluded that the data suggests that adjusting the dose of venetoclax while maintaining the dose of Revimenib may be the most logical strategy for future development. As we've previously communicated, we intend to initiate a pivotal trial with the striplet combination in newly diagnosed patients by year-end. Turning to slide six, At EHA, we also presented updated data from the Augment-102 trial of revimenib in combination with fludarbin-cytarbin, or FLA, in a predominantly pediatric population with relapsed refractory mutant NPM1, NIP98-rearranged, or KMT2A-rearranged AML. As of the data cutoff of 15 January 2024, 27 patients received FLA plus revimenib at 113 mg or 163 mg. Patients included in the trial were heavily pretreated with a median of three prior lines of therapy. 67% had prior fly containing regimens. 52% of patients achieved composite complete remission or CRC. The MRD negative rate among CRC patients was 71%. Furthermore, seven patients or 50% of responders proceeded to transplant once they had entered remission. As with the Venazer triplet, we just discussed Revimenib does not appear to alter the tolerability profile of the standard of care regimen. These two updated data sets presented at EHAF provide further support for combining Revimenib with different standards of care in the newly diagnosed as well as relapsed or refractory settings. Turning to slide seven, in March, we completed enrollment in the pivotal cohort of the Augment 101 trial with the enrollment of 64 adults and up to 20 pediatric relapsed or refractory NPM1 mutant AML patients. We are on track, 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 one portion of Augment 101, which showed that 50% of patients achieved a response and 36% achieved a complete remission or CR with partial hematological recovery. Notably, all patients with the CRCRH were MRD negative. Consistent with the KMT2A population, Revimenib also enabled patients in remission to proceed to transplant with durable responses, despite many of the patients having failed prior venetoclax therapy and stem cell transplant. These data also indicate that Revimenib is well-tolerated in patients with mutant MPM1 with an overall safety profile 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 eight of the preparations we've made on 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, 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 two agencies. We also continue to prepare for future NCCN guidelines submission for every minute that we anticipate will include the prescribing information as well as peer-reviewed publications and congress presentations. Of note, once the top line data in 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 tremendous progress driving scientific exchange with physicians at major centers of excellence across the country. We've also built a health economics and real-world evidence team focused on supporting the value of a portfolio, and we continue to increase engagement with patient advocacy groups. With that, I'll now turn over to Steve to talk about our commercial launch plans and the market opportunities. Steve.
spk03: Thank you, Neil, and thanks to everyone for joining us today. 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 healthcare providers. We are well prepared to execute on the exciting opportunities in front of us. Turning to revenue preparations in slide eight. Our goal simply is a strong launch, and we are ready to hit the ground running with Revumetiv 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 the hematology oncology space and a demonstrated track record of success. This team is in the field right now profiling 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 six 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 in approximately 2,000 centers with roughly 200 of those accounts representing more than two-thirds of the opportunity, enabling a concentrated effort. With our plan, we believe we should reach centers where 98% or more of potential relapsed refractory KNT2AR patients receive treatment. Now, another important thing we've done in preparation for the launch is develop advanced data mining capabilities appropriately identify patients' needs. 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 plans covering more than 90% of all covered lives, both commercial and Part D, prior to the anticipated approval. Payers tell us that they recognize the unmet need and appreciate the value that Revumenta provides. We believe plans will make their formulary decisions within six to 12 months of approval, and we'll work with them to expedite the review when possible. Importantly, given the urgent patient need, 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 companies. Turn to slide nine and the market opportunity. KMT2AR and NPM1 acute leukemias represent up to 40% of all AML patients. There are no FDA approved targeted therapies for this population. We believe relapse or refractory KMT2AR acute leukemia alone represents a total addressable market opportunity of approximately $750 million in the U.S. The annual incidence of KNP2AR acute leukemia is 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 nine 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 Revumentum early during an eligible patient's treatment journey to bring more patients to transplant and then extend responses by continuing with Revumentum monotherapy following transplant and graftment. We expect that our first move of advantage and the early experience physicians will gain treating patients with Revumentum will be vitally important to the long-term success of our brand. Our significant market share is likely to extend meaningfully beyond K-2AR especially as we will be the first to deliver meaningful pivotal data and other indications, such as NPM1 AML. We estimate that the two distinct market segments in acute leukemias, AMT2AR 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 visits and more, I've seen tremendous excitement and support for Revumentib, creating a momentum that I look forward to building on through our commitment to delivering an absolute best-in-class experience for healthcare providers and patients. Moving to Axotilamab in slide 10. The anticipated commercialization of Axotilamab will be led by the INSIGHT team, and will benefit from the deep experience and long-standing relationships that they've established through their work building the GBHD market with Jackify. We'll provide 30% of the sales effort, leveraging our own field force that we anticipate will carry two products with highly overlapping call points. Pave the way for a successful launch. Insight is continuing to drive engagement with payers and raise awareness of the distinct pathway that Axotilamab targets and the compelling outcomes observed in the UGAVE-201 trial, which we recently detailed. at the 2023 ASH Congress. Turning to slide 11. We estimate there are approximately 17,000 patients on treatment for chronic GDHD 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 two previous lines of treatment, which would be our target population for our first indication and represents an attractive initial opportunity. For instance, in the three years since the launch of Resiroc, another 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 to $2 billion, which assumes that patients will remain on therapy for over 12 months, and assuming axotilumab 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 axotilumab in earlier line settings for chronic GVHD and other diseases where we believe its 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.
spk17: Thank you, Steve. Turn to slide 12. As Michael mentioned earlier, the $455 million in cash equivalent and short and long-term investments on our balance sheet as of June 30th is expected to provide runway through 2026. Our financial strength allows us to fund the anticipated commercialization of two drugs and appropriately invest to continue to realize the value of our pipeline. Turning to the income statement, operating expenses in the second quarter was $77.7 million. and included $48.7 million of research and development expense and $29.1 million of selling general and administrative expense. We'd like to 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 to $75 million, and total operating expenses to be $105 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 to $260 million, and total operating expenses to be between $355 to $375 million. Please note that the guidance range for operating expenses for the full year includes an estimated $43 million of non-cash stock compensation expense, and that research and development expense guidance includes any milestones owed to our partners' potential drug approvals. Ahead of the upcoming launch of Exotilamab, I want to briefly review how we will recognize revenue for that partner and product. Slide 13 provides an illustrative example of accounting for sales of Exotilamab 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 axotelimab, as in the top example of the 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 axotilimab, 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 receive from Insight will be recorded as milestone revenue on our income statement. As a reminder, research and development expenses under our partnership, including regulatory and CMC expenses, are 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, INSET 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.
spk05: 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 two medicines. With the momentum we have built and our robust clinical development strategy designed to explore the full potential of Rebumentum and Axotilumab, 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 syntax. With that, I would like to open the call for questions. Operator?
spk09: At this time, I would like to remind everyone that in order to ask a question, press star and then the number five on your telephone keypad. If you would like to withdraw your question, press star and the number five once again. We'll pause for just a moment to compile the Q&A roster. Our first question comes from Anutan Rama from J.P. Morgan. Your line is open. Feel free to unmute.
spk18: Hi. Thanks for taking the question. This is actually Malcolm Kuno on 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 Accetonab and Revimen approvals?
spk05: Thanks for the question, Malcolm. Let me turn it over to Steve to address it.
spk03: Yeah, thanks, Malcolm, for the question. In terms of size, I think my 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 and 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 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 two things. One of them is profiling accounts. I mentioned the complex treatment journey. We want to understand for any given institution that we call on how they do business, how they see patients, how they're treated. There's a ton for us to learn from understanding how they test for KMT2AR, how those patients get highlighted for clinicians, how they like to deliver drugs. 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 in 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 treated. Second piece is the education piece. There is a little bit of a lift here for men inhibition from a 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, literally 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 high 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. Thanks, Malcolm.
spk09: Our next question comes from Chris Shibutani from Goldman Sachs. Your line is now open.
spk06: Hi, this is Kevin Strang on for Chris. Thanks for taking my question. Just wanted to talk about the combination studies for Revimenib in the second half. You said you'd have data updates. Could you just highlight and bookend what those will be? I believe there's going to be an update from the SAVE trial. And then also for the BEAT AML trial, can you talk about where you are with respect to establishing a recommended phase two 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. Thanks.
spk05: Right. So, Kevin, thank you. Maybe I'll address that. So, for the BDAML trial, the BDAML trial, I'll start there, is, as you know, we're looking for our recommended phase two dose. We've made tremendous progress, and at EHA we had presented the data on both of those doses. We have, in the process of filling out, at least those two doses just filling out the expected number of patients. And we're going to be making a choice at some point soon between the two doses, which is the recommended phase two dose. We'll be working through that over the next week. 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 SAVE trial, we, this again, this is Dr. Gus Ease's trial at MD Anderson. This is in relapsed refractory patients, a combination of Venn and Covi plus Revumeneb. We presented data, there was data presented last year at EHA, sorry, at ASH. So the investigators told us that there will be some updated presentation 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 it to be more patients, additional follow-up. And as you know, it was exciting data, so we're eagerly anticipating that as well. Great. Thank you. Thanks, Kevin.
spk09: The next question is from the line of Phil Nadeau from TD Cowen. Your line is now open.
spk12: I think this is Ernie Rodriguez for Phil. Thanks for taking our question. I have two quick ones. The first one is, even the overlap in the target treatment centers between Revu and Axan, 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 two launches? Can you see perhaps that maybe any benefit or any learnings that you can use to later accelerate the, the, um, the launch of came to a, uh, relative to, to what your internal estimates were. And then the second question is, um, for the intercept trial of revenue in revenue 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.
spk05: Great. Yeah, thanks for the questions. First, I'll ask Neil to address the trial question that you asked, and then Steve will address your commercial question.
spk15: Thanks. 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 aware, it is a third-party trial, and therefore, we don't control disclosure of data, but our understanding is that recruitment is going rather simply well. And, you know, we expect that the investigators will present data at a medical meeting in the future, but we don't have an exact timing on that. With that, I'll pass over to Steve for your first question.
spk03: Yeah, so just to reiterate, the first question was really, was there a benefit in an extra time, particularly with the overlap of the two compounds? So, yeah, I think just speaking and really speaking from experience, there's never been a launch where Someone, you know, in terms of the prelaunch period, do 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 Revumentum than we would have otherwise anticipated. The activity that I described before will enable us, you know, all the profiling and the mechanism of disease and disease state awareness work we're doing will put to good use over the, however long it takes us to get, you know, 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 able to leverage all that time. And I think the point made, there is tremendous overlap with the access to telemedicine opportunity. I don't think I shared the number of treatment centers for chronic TBHT, but we essentially covered them all by covering all of the revenue opportunities. And what I mean by that, there's 2,000 centers, both academic and community, that we're covering for AML and Revumetab, there's under 200 that you cover for transplant to support axotelomab. So we're already in those, essentially. So we're profiling those accounts as well. There's a lot of connectivity between Hemox and transplanters. And there's actually some advantages with Rev, particularly if 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 points 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 from now until either product comes to market.
spk12: Thank you. That's helpful.
spk02: Thank you.
spk09: Our next question comes from the line of Peter Lawson from Barclays. Your line is now open.
spk14: Hey, good afternoon. This is Alex on for Peter from Barclays. Thanks for taking our questions. 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, could we see initial phase one data from your seven plus three combination in 2024?
spk05: Alex, thanks for the question. 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 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. And then for the seven plus three phase one 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.
spk14: Okay, great. 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 one? Thank you.
spk05: Yeah, I don't think we've actually talked about the exact type of patients that we're enrolling. I think they're just newly diagnosed patients that with seven plus three in combination, yeah.
spk14: Thank you.
spk05: Thank you.
spk09: Our next question comes from the line of Brad Canino from Stiefel. Your line is now open.
spk04: Oh, hi. Thank you. This is Brad. Um, I, like, I think it would be good to clear up some of the sequence around the revumentum review. I think a lot of us presume that with our tour and the close FDA collaboration that that provides, plus your rampant 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?
spk05: Yeah, thanks, Brad. Um, and I think, uh, you know, we, we, we were able to catch up with many of, many of you, um, earlier in the week when the news came out. Look, I think this was unfortunate in the sense that we were in receipt of a few RFIs from, and this is an ongoing process under RTOR, you know, that's been going on since last year, where we submitted our NDA. And then since then, we've been receiving requests for information from the agency. The two, I'd say two 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 three-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. You know, this was something that we were prepared for, but, you know, they didn't ask for it. And then 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, you know, without events. So we were feeling quite confident in everything that we have not only been through with the agency, but what we submitted and heard back. 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, you know, I think a very good position to launch the drug before the end of the year.
spk04: Yeah, 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 Revumentive is consistent and that prior data cut remains reliable? Thank you. Yeah, thanks, Brad.
spk05: Look, I think the information, and I can, we don't get into the specifics of any one 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 would be required as well. This is not manufacturing information that they've looked for. It's a clinical package that is, in our minds, completely consistent and supportive of approval. This is not information that changes the profile, the risk benefit at all. And so we feel actually it's even more robust of a package than as previously, you know, worked on. It was 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 benefits. 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 present.
spk09: The next question comes from the line of Michael Schmidt from Guggenheim. Please go ahead.
spk13: Hey, guys. Thanks for taking my question. Maybe just a quick follow-up. So given that the Revumenib NDA obviously is still under RTOR review and with the extended PDUFA date until end of September now giving ample 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.
spk05: Yeah, Michael, thanks for the question. It's not unprecedented for even with the extensions. We've seen a couple of RTOR products, Resiroc being one that got approved under RTOR, got extended, actually got approved about six weeks earlier than than their extended time frame or their extended PDUFA. So we've seen our tour 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, you know, 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've specified.
spk13: Super helpful, thanks. And then unrelated follow-up, just sort of thinking about the upcoming registration data in MNPM1 patients later this year. In perhaps relative to KMT-JR, how should we think about the transplant dynamics in the NPM-1 subset? And, you know, related to that, what's a good modeling assumption for durational therapy for that market subset relative to KMT-JR? Thanks so much.
spk05: Yeah, thanks for the question. Look, I think NPM-1, our view has been all along that the NPM-1 data we've seen in the phase one trial looks very similar to what we've seen with KMT2A. There's a consistency across all the measures between the data sets. And 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. while the way that 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 if they're healthy enough and they've cleared their tumor to get them to a transplant. So again, that dynamic, we've seen that with NPM1 as well as we have with KMT2A. So You know, 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 one and now in our pivotal trial for KMT2A. Great, thank you. Thanks, Michael.
spk09: Our next question comes from the line of Kelly Shi from Jefferies. Your line is now open.
spk08: Hi, this is Clara. I'm for Kelly. Thanks for taking our question. Now that you will likely have a little data readout in MPM-1 that had approval in KMT-2A, I'm wondering how would that possibly change your discussion with the NCCN Committee for the Guideline Inclusion? And maybe, you know, one step forward also, what will be the conversation with payers going to be like upon this update as well? Thank you.
spk05: Yeah, Claire, 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 you know, proceed with potential guideline inclusion for, for NPM one. So that's the sort of cadence here. And there'll be some urgency to move in, in, in order to affect the fact that we have a, we have a drug on the market and then another indication in NPM one, which is moving through quickly through an S and D a process at the same time, but could be included in, in guidelines ahead of, uh, ahead of approval. So there will be, um, there will be, uh, you know, quite a bit of activity related to, uh, to not only getting the drug approved, but also moving guidelines through publications and conversations with thought leaders who work, you know, 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.
spk03: Yeah, I think part two is, you know, what is the impact on payers of NPM1? So you guys, in my opening comments, had talked about our activity with payers, which has been extensive. You know, we'll have talked to, you know, payers that cover 90% of managed care lives in both commercial and Part D. I think payers, they recognize the unmet need in KMT2AR, and they recognize it in NPM1. They like what they've seen with Revumenta, and, you know, given the price point in the space of roughly $27,000 to $32,000 a month, we believe we'll be at a slight premium to those agents. You know, it's an obvious connection between NCCN guidelines and payers. Payers like to see what's in the public domain. They want to see, you know, data published. They want to see, you know, the guidelines. Clearly, the entree point is KNT2AR. That's where we'll set price. I think payers, you know, want to service patients. You know, they'll produce, you know, some hurdles and obstacles, the front and barriers, which they always do with products like this. You know, we've got, you know, fantastic products. especially 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 formulary. 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.
spk08: Thank you. That was very helpful.
spk17: Thanks, Claire.
spk09: Next question comes from Egal Nachamovitz from Citi. Your line is now open.
spk02: Hi, guys. This is Ashok Mubarak. I'm for Egal. Thanks for taking my questions. I just wanted to ask one on axotilumab. 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 DLA process. Have you reached label negotiations? Was there anything of value with the maybe mid-cycle review? Anything to sort of confirm that DLA is on track would be very helpful. Thank you.
spk05: Yeah, sure. 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.
spk02: Okay, maybe one follow-up on that then. Should we sort of expect the commercial launch to take place maybe immediately after a potential approval of Axotelamab, or is there a reason to sort of think there might be a little bit of a lag, maybe waiting for Revimenib, so there's some synergy with that commercial launch as well? Thanks.
spk05: Right, so no, thanks for the follow-up, Asher. 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.
spk02: Got it. Thank you very much. Thank you.
spk09: Our next question comes from the line of Kalpeet Patel from B. Riley. Your line is now open.
spk07: Yeah. Hey. Good afternoon and thanks for taking the question. Maybe one for Ravi Menon. Is there anything that you learned from the KMP2AR regulatory filing here that could be beneficial for the NPM1 filing and help streamline that? I know the timeline says first half 25 instead of maybe first quarter 25. Is there a reason for that? And then I have a follow-up.
spk05: Yeah, thanks, Cal. Let me turn it over to Neil to maybe take a crack at that.
spk15: Yeah, thanks for the question. So the straightforward answer to your question is yes, right? 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 SMDA. So in the NDA, we do, you know, a lot of the heavy lifting is done, and any subsequent application, supplementary application, is much more straightforward. So, you know, we're obviously excited and looking forward to getting the NPM1 data during the fourth quarter, and you can be assured that we will be filing or submitting those data as expeditiously as possible. There was a part of your question I missed. Did I address all of your questions, or is this something I missed?
spk07: Yeah, it just says first half 25, first quarter 25 for filing for the NPM-1 COVID.
spk15: Yeah, we haven't been that specific with our guidance yet, but you can be sure that we will be working pretty hard at it. I'll pass it back to Michael.
spk05: Cal, your second question?
spk07: Yeah. Yeah. So and then the second question is sort of related here. Was there the information that was requested by the FDA, I guess, was any part of the NPM one cohort data set that was sent to the FDA for this update?
spk05: No, Cal, but I would actually just focus on the KMT2A submission. That's what we're working with the FDA on 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.
spk07: Okay. Thanks for getting the questions. Thank you.
spk09: Our next question comes from the line of Justin Zellin from BTIG. Your line is now open.
spk16: Thanks for taking our question. Michael, I'd like to clarify regarding your confidence on the Revenue Management 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 Revenue Management could be approved under an accelerated approval basis?
spk05: Justin, thanks for the question. 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 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 three months. It doesn't change the process at all in terms of what we're filing for, what we're likely to have at approval.
spk16: Great. Thanks for clarifying and taking our question.
spk05: Thanks, Justin.
spk09: The next question comes from the line of Jason Szymanski from Bank of America. Your line is open.
spk11: Good afternoon, and this is Cameron Bozdog on for Jason. Congrats on the progress, and thanks so much for taking our question. So looking ahead to the potential near-term launch of axotelamab, can you maybe comment on your internal market analyses 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 docs, especially when you think about the route to administration? Thank you.
spk05: Great. Thanks for the question. I'm going to turn it over to Steve to address it.
spk03: Thanks for the question, Kim. 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 from a treatment center standpoint, I think I may have provided the numbers earlier, 10% of the centers, it's under 200. So it's all driven by that. I think in the part of who the drivers, academic versus community, it's the biggest centers that are going to drive all this. For the most part, certainly at launch, there'll be some awareness, you know, outside of that. And even within the 200 center, there's probably 35 that see half the patients in the country. So it is as, you know, 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, you know, speaking to market opportunity, there's a lot of business here. There's a lot of unmet need and dissatisfaction in the current treatment, you know, GVHD population. they want more, they need more agents. It's a really insidious disease. So it'll be, you know, 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 bullets, but the market's ready and we'll be ready shortly too. And I think it'll be well received by physicians and patients.
spk09: And our final question comes from the line of George Farmer from Scotiabank. Your line is open.
spk10: Hi, this is Chloe Young for George. Can you hear me okay?
spk05: I hear you, Chloe. Thank you.
spk10: Yeah, the two from us. So based on your initial data package for ReviManage, so you said that FDA did its thing and ODAP was necessary. Do you still believe now to be the case? So how confident are you that the additional information is submitted that prompted the proof extension will not be subject of an ODAC review in the next six months? And the second question is, Michael, you mentioned BB in your prepared remarks. So I'm just curious what types of BB deals you had in mind, examples of areas of interest, those types of assets you're eyeing at the moment, both as a buyer or even a target. And if you could maybe put it in context to give the inside relationship for us and tell us kind of how you see that evolving over time.
spk05: Chloe, 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 augment the package that we've submitted. So there's really, there is, in our mind, and based on what we've heard from the agency, there doesn't seem to be any risk of an ODAC that we know of. So I feel quite confident about that. And then in terms of BD, which is an interesting question, and it essentially relates to how do we, you know, grow the pipeline and continue doing what we do well at Syndex in part, which is in licensing of or acquiring new molecules to, add to the pipeline. 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 potential. But at this point, it's hard to speculate on development transactions until they're done and closed. So, but whatever we do will be, it seems, of an earlier variety. So, we're not looking to take on late stage projects. Earlier projects are the type of the, you know, types 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 Axotilimab and for Revimenib. It's a balanced strategy and one that we are actively engaged in.
spk10: Okay, thanks. With respect to the partnership with Insight, do you have any thoughts on how you see that evolving in the future?
spk05: Our partnership with Insight 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 axotilamab in a variety of indications earlier in the treatment course for GVHD. We're pursuing IPF. So that's, you know, these are, this is a global partnership with Insight, and so it's gone quite well. And we, you know, continue to believe that it will expand and continue in perpetuity in the way we envisioned it to start. We're very happy with that.
spk10: Thank you.
spk05: Thank you, Chloe.
spk09: 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.
spk05: 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.
spk09: And we're now on a private line.
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