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Syndax Pharmaceuticals Inc
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Good day, everyone, and welcome to the Syndax Second Quarter 2023 Earnings Conference Call. Today's call is being recorded.
At this time, I would like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndax Pharmaceuticals. Please go ahead.
Thank you, Operator. Welcome, and thank you all for joining us today for a review of Syndax's second quarter 2023 financial and operating results. I'm Sharon Klahre, and with me this afternoon to provide an update on the Company's progress and discuss financial results are Michael Metzger, Chief Executive Officer; Dr. Neil Gallagher, President and Head of R&D; and Keith Goldan, Chief Financial Officer. Also joining us on the call today for the question-and-answer session are Dr. Peter Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Business Officer.
This call is accompanied by a slide deck that has been posted on the Investors page of the Company's website.
You can now turn to our forward-looking statements on Slide 2. Before we begin, I'd like to remind you that any statements made during 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 may represent our views as of today, August 3, 2023, only. A record of this call will be available on the -- a replay of this call will be available on the Company's website, www.syndax.com following its completion.
With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer, of Syndax.
Thank you, Sharon, and thank you all for joining the webcast.
This is a transformational time for Syndax. We are making excellent progress executing on our milestones and corporate priorities, all of which put us on a path to becoming a commercial stage biopharmaceutical company with two potentially best-in-class products.
Throughout the second quarter, we continued to deliver on our development strategy and we started off the third quarter in a great position having recently reported positive pivotal AGAVE-201 data of axatilimab in chronic graft-versus-host disease. We look forward to presenting the full AGAVE-201 dataset at a future medical meeting.
As you can see on Slide 3, we are looking forward to reporting data from the KMT2A population of the AUGMENT-101 trial of revumenib in acute leukemia later this quarter. Further, we expect to have data from several of our trials of revumenib by year-end, which we believe could meaningfully add to its value proposition and support its best-in-class profile.
Once we have pivotal data from both revumenib and axatilimab in hand, Syndax will be in a very unique position as a smid cap company with the opportunity to submit two potential regulatory filings by year-end and if approved launch both drugs in 2024.
We are well funded with $418 million in cash and equivalents as of June 30. This amount of cash not only funds our planned commercial launches and the trials we have laid out on Slide 3, but also enables us to expand beyond our core registration indications and selectively pursue business development opportunities.
We continue to evaluate earlier stage targeted oncology compounds to add to our pipeline, but as we have previously conveyed our bar for consummating a transaction is high as any new opportunity would need to be differentiated and create substantial future value to align with our long-term corporate strategy.
Let's now turn to Slide 4 to dive into revumenib our highly selective menin inhibitor. Our pivotal AUGMENT-101 trial evaluating revumenib in patients with relapsed/refractory NPM1 mutant or KMT2A rearranged acute leukemia is ongoing. We continue to expect to report data from the -- from KMT2A rearranged acute leukemia patients in the AUGMENT-101 pivotal trial in the third quarter of this year, which could serve as the basis for a U.S. regulatory filing by year-end.
The Phase 2 portion of AUGMENT-101 was designed as three single arm pivotal trials with distinct patient populations that enroll independently. These populations include KMT2A rearranged ALL, KMT2A rearranged AML, and NPM1 mutant AML. Each trial is enrolling patients age one month or older. The primary endpoint of these -- of each of these is the percentage of patients achieving CR/CRH with secondary endpoints including durability of CR/CRH response, transfusion, independence, overall survival and safety. Patients who undergo transplant have the opportunity to continue treatment with revumenib following successful engraftment, which could be an important maintenance option for these patients, given that that they are at a high risk relapse.
As a reminder, in the Phase 1 experience, we have had patients remain on treatment and in response for nearly two years, which is possible due to revumenib's compelling safety and tolerability profile. As previously reported in December 2022, we received breakthrough therapy designation covering all KMT2A rearranged acute leukemia patients. In subsequent conversations with the FDA, we reached agreement whereby we will pool a subset of data generated from the AML and ALL KMT2A cohorts into a single NDA filing aimed at an indication to treat adult and pediatric relapsed/refractory acute leukemia patients with a KMT2A rearrangement. We expect to provide top-line data in relapsed/refractory adult and pediatric KMT2A patients this quarter and to file an NDA for this population by the end of 2023.
Our goal for the top-line data disclosure will be to provide enough data on efficacy and safety so that all stakeholders understand the drug profile while still preserving enough of the details for presentation at a future medical meeting. The top-line release will likely include the primary endpoint along with secondary endpoints of interest.
Separately, we continue to enroll relapsed/refractory NPM1 mutant AML patients and expect completion of enrollment of this cohort by year-end. As we look at the competitive landscape and engage with experts in the field, we believe revumenib's compelling clinical profile as demonstrated in the robust Phase 1 experience published in Nature in March and highlighted on Slide 5, physicians revumenib to not only be a first-in-class but also a best-in-class treatment.
As a reminder, the Phase 1 AUGMENT-101 data demonstrated that in patients who received a median of four prior therapies, the CR/CRH rate in both the KMT2A and NPM1 subsets at the RP2D was 27% with a median duration of response of 9.1 months. Experts in the field also point to the high MRD negative rate of 78% among patients achieving a CR/CRH since MRD negativity is associated with improved outcomes of potential curative bone marrow transplant.
While the Phase 1 trial wasn't designed for re-treatment following transplantation, several of these patients went on to receive revumenib maintenance therapy in the compassionate use setting and thus we included this option in the pivotal portion of the AUGMENT-101 trial at the request of the treating physicians.
Turning to Slide 6. We believe that revumenib could become the backbone of treatment for patients with KMT2A rearrangement and NPM1 mutant acute leukemias. Based on revumenib's compelling efficacy and safety profile, our clinical strategy has expanded beyond the relapsed and refractory setting into earlier settings and post-transplant maintenance including combinations with approved therapies.
In addition to the clinical trials that Syndax is conducting, we are working with cooperative groups and leading investigators to further accelerate the generation of evidence of clinical benefits seen with revumenib across various settings of KMT2A and NPM1 acute leukemias.
Let me take a minute to highlight these for you. Starting with the Phase 1 BEAT-AML umbrella trial. Revumenib is being combined with VENCLEXTA and azacitidine to treat newly diagnosed AML patients who are unfit for induction chemotherapy as part of our collaboration with the Leukemia and Lymphoma Society. Enrollment is ongoing and we continue to expect to receive data on safety at a potential RP2D from the trial by the year-end 2023.
The AUGMENT-102 trial is designed to assess the safety of revumenib in combination with standard salvage chemotherapies for patients with relapsed or refractory acute leukemias. We expect to provide an update on the initial safety data and potential RP2D from the trial by year-end 2023. The SAVE trial is an interesting combination trial of all -- of an all oral regimen, revumenib with VENCLEXTA and INQOVI and oral hypomethylating agent in relapsed/refractory acute leukemia being led by Dr. Issa at MD Anderson Cancer Center.
And the INTERCEPT trial is enrolling patients as part of the master clinical trial led by the Australasian Leukemia and Lymphoma Group. It is designed to explore the activity of revumenib as monotherapy maintenance in patients with AML who have MRD positive disease following initial treatment.
And finally, we plan to initiate a trial of revumenib in combination with standard of care intensive chemotherapy known as seven plus three in newly diagnosed patients with acute leukemia by year-end 2023. This trial will also include an option for maintenance with revumenib's monotherapy.
Turning to Slide 7 . There are currently no FDA approved therapies targeting KMT2A or NPM1 acute leukemias, a population that together represents up to 40% of AML patients. Including the expansion opportunities, we see the potential to address upwards of 12,000 NPM1 and KMT2A acute leukemia patients across various settings. This is an area of significant unmet need and we are committed to bringing these encouraging clinical benefits to even more patients.
In addition to the market opportunity in acute leukemia, we are also exploring the use of revumenib as a treatment in solid tumors based on compelling preclinical signs supporting the role of menin-MLL1 interaction in beta-catenin driven tumors. To that end, we are enrolling a proof of concept signal seeking Phase 1 clinical trial in metastatic colorectal cancer. The trial is proceeding through the dose escalation phase and we would view responses or stable disease as promising in this difficult patient population. We expect to provide an update on the progress of the Phase 1 trial before year-end 2023.
I will now ask, Neil, to provide a brief recap of our recently reported pivotal data for axatilimab. Neil?
Thank you, Michael.
Moving now to axatilimab on monoclonal antibody targeting the CSF-1 receptor beginning on Slide 8. I'll provide a brief recap as I expect that many of you joined us for the recent data call. Last week, we shared positive results from the global pivotal AGAVE-201 trial evaluating the efficacy, safety, and tolerability of axatilimab in 241 patients with active chronic GVHD whose disease had progressed after at least two prior therapies.
All three dose cohorts of AGAVE-201 met the primary endpoint of overall response rate by cycle seven day one using the 2014 NIH consensus criteria for chronic GVHD. Patients were stratified at baseline based on prior exposure to ibrutinib, ruxolitinib or belumosudil as well as disease severity, and then treated on progression.
The primary endpoint of the AGAVE-201 trial was objective response rate by cycle seven day one or six months of treatment. The trial randomized patients to one of three treatment codes, each investigating a different dose of axatilimab. These were 0.3 milligrams per kilogram or 1 milligram per kilogram every two weeks and 3 milligrams per kilogram every four weeks. Because macrophages play an essential role in maintaining physiological homeostasis, these regimen were chosen to allow time for recovery of the macrophage population, thereby potentially minimizing adverse events by maintaining robust efficacy. The 0.3 milligrams per kilogram dose was selected in consultation with the FDA as an intermediate dose to represent the lower end of the range that was explored in our Phase 1 trial, but responses were observed in patients who received 0.15 and 0.5 milligrams per kilogram every two weeks.
This is all supported by PK/PD data from a previous axatilimab Phase 1 trial in healthy volunteers. After six months on trial, patients at the 0.3 milligrams per kilogram and 1 milligram per kilogram doses at the option to switch to a dose proportional once monthly regimen.
Turning to Slide 9. I want to reemphasize rather our excitement around the overall success of the trial. All three cohorts in the AGAVE-201 pivotal trial met the primary endpoint of overall response rate. The response rate was 74% in patients treated at 0.3 milligrams per kilogram every two weeks, 67% in patients treated at 1 milligram per kilogram every two weeks, and 50% in patients treated at 3 milligrams per kilogram every four weeks.
While we have not yet analyzed exposure response relationships, these data support our belief that lower doses given every two weeks provide a greater opportunity for macrophage recovery between doses and may be key to improved tolerability as well as higher response rates, particularly at the 0.3 milligrams per kilogram dose level.
As I just mentioned, at the 0.3 milligram per kilogram dose level, the response rate by cycle seven day one was 74%. Moreover, the observed responses were durable with the median duration of response not yet reached at the time of data cut all. 60% of patients who responded to axatilimab were still responding at one year. The responses were accompanied by a reduction in symptom burden as measured by the modified lead symptom scale. Axatilimab was well tolerated with a low rate of discontinuation, and the most common adverse events were consistent with the on-target effects that were observed in prior trials.
On Slide 10, I'd like to highlight that robust efficacy was observed despite the fact that these patients were very advanced and heavily pretreated. It is notable that patients included in the AGAVE-201 trial were more advanced and more heavily pretreated than patients included in pivotal trials of the approved agents. This slide shows a cross study comparison with ROCKstar pivotal trial of Rezurock that targeted a similar population of patients with chronic GVHD who received two or more prior lines of therapy. As you can see, there were meaningful differences in patient populations between the Rezurock ROCKstar trial and the axatilimab AGAVE-201 trial. Patients in the AGAVE-201 trial had a longer median time since diagnosis, more severe chronic GVHD, and had received more prior lines of therapy, including a greater number of patients that received Jakafi. We believe that these important points of differentiation, which underscore the how impressive the AGAVE-201 trial results are and point to the significant value axatilimab could bring to patients if approved.
I'll now turn the call back to Michael.
Thank you, Neil.
Slide 11 details the market opportunity for axatilimab. We estimate that approximately 14,000 U.S. patients suffer from chronic GVHD, 50% of whom require treatment beyond second line due to disease progression, inadequate response or disease manifestations that aren't fully addressed with current treatments. There are unfortunately no cures for this advanced population of chronic GVHD patients.
Following initial treatment with corticosteroids patients are cycled through a variety of additional therapies. Essentially, patients may be treated with several of the approved therapies, though the order in which they're used may depend on the physician's experience with how a given agent may address specific manifestations of the disease.
The successful commercial launches of Jakafi and Rezurock speak to the unmet need in chronic GVHD that translates to a large commercial opportunity. We believe that axatilimab could provide a differentiated, effective and practice changing intervention for this underserved population. Axatilimab's ability to suppress monocyte derived macrophage activation and proliferation may provide more comprehensive control of the disease than currently approved therapies. Not only is this a key differentiator, but it also supports moving axatilimab earlier in the treatment paradigm to potentially prevent organ damage before it occurs. Axatilimab's unique mechanism of action may also offer the advantage of being an ideal combination partner with standard of care therapies currently used for the treatment of chronic GVHD, as there are no theoretic concerns in terms of drug-drug interactions and overlapping mechanisms of action. Combinations in earlier settings both in adults and pediatrics, as well as the opportunity to expand to the ex-U.S. markets could build significant additional value for axatilimab in chronic GVHD.
I'll now turn the call over to Keith to review our financial results. Keith?
Thank you, Michael.
Let me take a few minutes to discuss our financial results for the quarter ended June 30, 2023. Turning to Slide 12, the results of our operations for the second quarter of 2023 and the comparison to the prior year's quarter are included in our press release, so I won't repeat them in these remarks.
Additional financial details are available in our second quarter 2023 report, which was filed earlier today on Form 10-Q. I would like to point out that our net loss for the second quarter was $44.6 million or $0.64 per share compared to a net loss of $37.6 million or $0.62 per share for the comparable period last year. This difference in our net loss was largely driven by an increase in employee-related expenses and professional fees within both SG&A and R&D.
We ended the second quarter with $418.3 million in cash equivalent and short and long-term investments, and 69.7 million shares and pre-funded warrants outstanding. Our balance sheet is expected to provide runway into the second quarter of 2025, which allows us to appropriately invest to maximize the value of our pipeline and pursue potential business development opportunities to build the pipeline. Importantly, it will also allow us to transition into a commercial stage organization in 2024.
Looking ahead, I'd like to provide financial guidance for the third quarter and full-year 2023. For the third quarter of this year, we expect GAAP research and development expenses to be $39 million to $43 million and total operating expenses to be $57 million to $62 million. For the full-year 2023, the company continues to expect research and development expenses to be $160 million to $175 million and total operating expenses to be $225 million to $240 million, which is inclusive of approximately $30 million of non-cash stock compensation expense.
With that, let me now turn the call back over to Michael.
Yes. Thank you, Keith.
Before opening up to questions, I'd like to briefly summarize what we presented today. In the near-term, we remain highly focused on delivering quality data readouts for our pipeline. We are looking forward to reporting our next pivotal readout data from the KMT2A population in the AUGMENT-101 trial later this quarter.
We expect pivotal data will serve as the basis for potential U.S. registrational filings by year-end 2023 for our two lead drug candidates both of which have the potential to make a significant impact on patient care in each setting and build considerable market share.
In addition, we continue to explore ways to capture the maximum value of our current pipeline by expanding into opportunities beyond the initial registration indications. In doing so, we aim to bring the encouraging clinical benefits of our lead candidates to even more patients in need.
It has been an exciting year-to-date for Syndax and we expect this positive momentum to continue in the coming months with critical value generating milestones on the horizon.
I remain confident that we have the expertise and resources to execute on our goals and on the strategic long-term vision that will allow us to successfully transition to a commercial stage biopharmaceutical company. As always, I would like to express our sincere appreciation to the Syndax team, collaborators, and most importantly the patients, trial sites and investigators involved with our clinical programs. It is all of you who help us to achieve our mission of realizing a future in which people with cancer live longer and better than ever before. And I'd also like to thank our committed long-term investors who continue to share in our vision and support us in building Syndax.
And with that, I'd like to open the call for questions. Operator?
[Operator Instructions].
The first question today comes from Phil Nadeau with TD Cowen. Please go ahead.
Good afternoon. Thanks for taking our questions and congrats on the progress. A couple from us. First on the upcoming pivotal data in the KMT2A cohort. Have you disclosed the statistical requirements for that cohort to be positive? Is there a response rate that has to be excluded or below the lower bound of the 95% confidence interval in order for the data technically to be positive?
Yes. Thanks, Phil for the first question. We have not disclosed the lower bound nor the target rate. So the statistics we haven't talked about. I think what people have asked us, sort of what's the regulatory bar, which of course is a little bit of an open question. And generally, our guidance is that we look at the precedent of what has been approved in the space in AML and I think the lower end of that guidance has been about 20% CR/CRH and obviously people have done better than that somewhere between 20% and 30%, but we haven't given specific guidance on the lower bound and what the target is for the trial.
Great. And second question on the pivotal study, I think most investors are going to use the KMT2A data as a proxy for what will be shown in the NPM1 population next year. Is there a reason why we shouldn't do that? Do you think that is a fair assumption that what you show in KMT2A is likely to be repeated in NPM1?
Thanks for the question, Phil. Yes. Look, I think our Phase 1 experience was that the data looked the same very similar. The point estimate was 27% at the RP2D. So that rationale would make some sense to us. And so sure, I think it's reasonable to think that they would be roughly the same.
Great. And then last question from us, on BEAT-AML, the press release says that Syndax is going to receive the safety data in the recommended Phase 2 dose by the end of 2023. Do you plan to disclose it when you receive it, or is there a specific venue at which investors will learn about the initial results from BEAT-AML?
Yes. Thanks for that question. Phil, the BEAT-AML trial is obviously a cooperative group trial, and so we have close collaboration with that group. We have the expectation that we will have some information related to safety and the RP2D before the end of the year, and we will look for a way to communicate that appropriately but we haven't committed to what venue that will be done at.
The next question comes from Anupam Rama with JPMorgan. Please go ahead.
Hey guys, thanks so much for taking the question and congrats on the progress and look forward to the upcoming updates. Maybe two quick ones from me. So as we think about AGAVE-201 data, the full update later this year, can you remind us of what additional analysis you're thinking about presenting later in the year that could provide some insights on the emerging profile of axatilimab? And then, what do you think the Street is kind of missing on the market potential of axatilimab? Michael, maybe following-up on your sort of opening comments and what are the key underappreciated levers here in terms of the market? Thanks so much.
Great. Thanks, Anupam. So maybe the first question related to the AGAVE-201 trial and the full update maybe I'll ask Neil to cover that, please.
Sure. Thanks, Michael, and thanks for the question. So we have not added that disclose, for instance, response rates by disease by organ graft affected. We haven't disclosed response rates by prior therapy, for instance, although we don't think that -- we think that given the extent of prior therapy in the high overall response rate, that that there would be anything concerning in there that we haven't signed -- we haven't disclosed yet.
And our plan, as I mentioned, we haven't perform the exposure response analysis as yet. We expect to be able to do all of that at a meeting in the future. So -- and on top of that, we will dispose whatever data we have to hand that that could be of use to the prescribing community, obviously in discussion with their partner and so.
Right. And maybe the second question Anupam was related to market potential and what the market may be missing relative to what we presented thus far. And maybe I'll ask Anjali to address that.
Okay. Thanks, Michael. Thanks, Anupam. As I think we've said and Michael said in his prepared remarks, the current estimate is there's about 14,000 patients living with chronic GVHD in the U.S. today. We believe at least 50% of them will advance to the third line setting and beyond. And that was a population we enrolled in the AGAVE-201 trial and what we expect to have for a label for axatilimab.
And I think what we showed in the top-line release last week is that axatilimab is very effective in patients with refractory chronic GVHD and in a population which mimics the current real world treatment paradigm over 70% of these patients had seen prior rux, and 25% to 30% had prior Rezurock and ibrutinib exposure. So despite enrolling a population of very severe chronic GVHD with extensive time since diagnosis and multiple product therapies, the drug was extremely tolerable, especially at the 0.3 mg/kg dose with a very low rate of discontinuations.
The effects are meaningful and durable, and we know physicians are excited about this profile and eager to have axatilimab as an option for their patients. The fulsome dataset from AGAVE as Neil just talked about is likely to provide more exact differentiation for axatilimab, but based on what we know about its differentiated mechanism targeting monocytes and macrophages versus cytokines and signaling pathways provide the potential to deliver a disease modifying treatment for patients and gives us confidence that axatilimab will be seen as a very important tool for treating refractory GVHD.
And as Michael said, we know its profiles and antibody enables safer combinability and can extend its promise to deliver disease modifying effect to earlier patients. And we'll be working on that trial and generating that data over time, but even today, we think there's going to be a significant value that axatilimab brings to these patients.
Anything else, Anupam?
Thanks so much for taking our questions.
Yes. Thank you.
The next question comes from Yigal Nochomovitz with Citi. Please go ahead.
Hi team, this is Ashiq Mubarack on for Yigal. Thanks for taking my questions. It sounds like the upcoming data for the KMT2A cohort will be more of a top-line release and we'll get the CR/CRH data, but I'm curious if we'll get a breakdown by leukemia type and more importantly, will the top-line release include a look at median duration of response? Thanks.
Yes. Thanks for the question. So look, I think our goal here is to provide, as I said in my remarks, provide meaningful information in the top-line such that physicians and stakeholders can really understand the profile of the drug. There will be information that is not included in the top-line.
I think primary endpoint being set your age and duration are likely to be part of that release. And the -- but I think beyond that, it's hard to say at this point what will be provided, but we know we're pretty attuned to what people are looking to see, and we'll hope to provide that as much as possible in the top-line.
Okay. I understand. Maybe one operating question. It does seem like you spent less on OpEx than you were sort of guiding for the second quarter. I'm just curious if anything in particular drove that and given your full-year guidance is unchanged. I'm just wondering how we should be thinking about spend for the rest of the year and maybe if we should be sort of assuming the lower end of the range. Thanks.
Yes. Thanks for the question. I'll ask Keith to address that.
Yes. So regarding the second quarter Yigal -- I'm sorry, not Yigal. Regarding the second quarter, there's remarks in the press release and in the Q that spoke to some lower spending on manufacturing call it CMC that was primarily timely -- timing issue. So we commented in the Q how that was part of the contributor to a lower spend in R&D expense in the second quarter, which led us to come in under guidance.
With respect to your question on full-year, appreciate that we did come in, in the quarter under, but yes, I would just look to us reaffirming the full-year guidance and not going to make further comments for the -- for R&D and OpEx beyond that.
The next question comes from Brad Canino with Stifel. Please go ahead.
Good afternoon. As you've talked about in your remarks, the revenue restarts after transplant and that post-transplant durability number will be important information. And I think it's going to take time to gather those data after the top-line release this quarter. So in the interim, what have you learned in the real world as you've done your diligence about rates of FLT3 and IDH inhibitors, specifically in the relapsed/refractory setting, in the post-transplant setting, in terms of the proportion that of patients that get restarted and how long they stay on those therapies? Thank you.
Yes. Brad thanks for the question. Let me ask Anjali to comment on that, that question.
Yes. Sure. Thanks Brad. So I think the difference between the -- so in the relapsed/refractory setting, neither the IDH inhibitors nor the FLT3 inhibitors had meaningful transplant rates, and so there weren't many patients that actually would go, had the opportunity to go back on therapy. And I think that's where our molecule revumenib is bringing a very differentiated profile and opportunity to extend treatment duration and really prolonged benefit for these patients.
Okay. And maybe just another question on clarification. For the BEAT-AML triplet, when you say safety and RP2D, does that mean or mean to imply that you will not receive drug activity data? Or does it imply that you believe the focus of the data given it's a Phase 1 should be on safety?
Yes. Brad, I think it's the latter. Thanks for the question. I think what we were trying to -- this is a Phase 1 dose escalation trial, right? So the focus is always on safety. We're pretty consistent in saying so in Phase 1 and obviously we're trying the goal is to get through dose escalation, get to an RR2D, and we hope to inform on that experience before the end of the year.
Yes. Okay. But I do have several investor conversations that reference like the FLT3 and IDH triplets, where those Phase 1 results were 90% plus CRs high rates of MRD negativity. So I want to know from you, are these the right precedent comps to think about for your triplet at this stage? And what other caveats would you suggest we think about as we try to compare those data?
Yes. I think Brad, you're -- I mean, it's going to be tricky with a small patient population when you're adding onto an already effective therapy to really see meaningful differences above and beyond. So we obviously think there's going to be a benefit from the triplet, but whether it plays out exactly where the enhancements are in a handful of patients, I think is what we're waiting to see.
Yes. I think just to add on to Anjali -- what Anjali was saying, I think we need to caution everyone to again these are late line patients or sorry, they're early patients, but they're not a lot of them. So we're not going to assume too much on the efficacy side. I think this is again is -- we'll see efficacy, but we're more intent on obviously how the drugs combine and if we can get to an RP2D that's meaningful.
The next question comes from Michael Schmidt with Guggenheim. Please go ahead.
Hey guys, thanks for taking my questions. I had a few follow-ups along the same lines. So in AUGMENT-101 in the KMT2A cohort -- in the pivotal cohort, is the percentage of patients receiving transplant and subsequent maintenance similar to that in your Phase 1 study. And I'm just thinking about in terms of the DOR in the pivotal study.
Right. Thanks for the question, Michael. So just a reminder, so in the Phase 1, we didn't have patients going back on drug post-transplant. That was not part of the protocol. So one of the major changes between Phase 1 and Phase 2 portion of the AUGMENT trial is that in Phase 2, we were able to have patients go back on treatment post-engraftment, so that is the a major change. And obviously, when you measure duration of therapy, meaning duration will account for the fact that patients go, it really goes -- you're measuring how long patients stay on therapy until relapsed. So it's -- that's really the measure. And that measure includes whether or not they go to transplant. So they're not censored at the time of transplant, they continue it's as if they're on one line of therapy.
So there'll be patients who receive therapy and don't get transplanted and progress. There'll be patients who get transplant and continue on and don't get retreated with revumenib. And then there'll be some patients who obviously get transplant and then get retreated with revumenib and then stay on treatment and will track those as well. So there'll be different experiences in the Phase 2, all I would say some of those patients enabled by the fact that they're able to go back on treatment and be treated as maintenance.
Got it. Understood. Thanks. And then regarding the question, the regulatory bar, the efficacy hurdle is -- my question is the efficacy hurdle in relapsed/refractory AML in the mNPM1 subset different than in the KMT2A subset given some overlap they are with FLT3 and IDH mutations for other treatments are available?
Yes. Thanks for the question, Michael. I think the -- of course, there are no drugs that are approved specifically for either NPM1 or KMT2A in the relapsed/refractory setting. I would make this comment at with fourth fifth line patients, once they get to that really refractory stage of their disease; our view is that, there the hurdle rate for approval is likely to be similar. Now again, we haven't provided the statistics of our trial, but they are each of the individual cohorts do have the same number of patients in them.
So that should give you some understanding that our statistics are set up in the same way. So again, I think regulatory precedent in AML is one thing. And you can maybe do something from the construction of our trials as well.
Okay. Super. And then lastly, so on the BEAT-AML safety data later this year or early next I guess, if you see the safety data, what frequency of adverse events or what type of safety profile would you view as acceptable? Is there a particular rate of thrombocytopenia, for example, that that you would view as some of the upper end of what's acceptable in order to advance in this constellation into registration study?
Yes. Thanks for that last question. So I would just say this at this stage before we have data and before we've actually disclosed anything, we will be looking at the totality of the data and obviously the safety and tolerability is going to be really, really important to understand how these drugs combine. We're not sort of a priority looking for any one particular side effect. I think the drugs we think in our mind should combine nicely. And so we'll have to see what the overall profile looks like at the time that we present the data.
The next question comes from Peter Lawson with Barclays. Please go ahead.
Great. Thanks so much. Just to again follow-up around the GVHD side of things, just when we should expect the full dataset there, if that's kind of an ASH event. And if there's kind of what we should be focused on around that dataset if it's the kind of the differentiation kind of starts emerging between you and Rezurock.
Yes. Yes. Thank you, Peter. Thanks for the question. So without giving away exact meetings, because we tend not we haven't disclosed what exact -- what meeting that dataset is likely to be presented at, but we did say before the end of the year is our target. And so I think that's probably an indicator of where that'll be. And then maybe I'll ask Neil to follow-up on the question about additional information and differentiation.
Yes. Thanks for the question. Well, I already pointed to the fact that we would -- we haven't yet disclosed for instance responses across affected disease organ classes. And I would anticipate that when we get to presenting data at a medical meeting, that those data will be included. Just to recap, and as we alluded to during the prepared remarks and the presentation, the population that was included in the AGAVE-201 study was really heavily more severe and more heavily pretreated than those patients included in prior pivotal studies with the approved agents.
So I won't reiterate all of the data points, but in terms of disease severity, as I've mentioned, the number of prior therapies, the time from diagnosis but also I would point to the safety data that we've already disclosed and particularly the low rate of discontinuation, particularly 0.3 mg/kg Q2 weekly we're only six patients discontinued as a result of adverse events. And I think you can expect as I said a more extensive data disclosure at that meeting. And we'll make every effort with our partner insight to include all of the relevant information that could be helpful to you and the medical community on patient.
Great. Thank you. And then just on the NPM1 side of the story, kind of when should we expect to see that data in I guess 2024, and is that kind of before or after a potential filing for the KMT2A approval in AML?
Yes. Thanks for the question, Peter. So NPM1, we -- our guidance is 2024. We haven't narrowed that at this point. And in terms of -- I'm sorry, what the second part of your question?
If that, kind of trying to narrow it down actually, whether it comes before or after the potential filing of KMT2A.
Right, of course. So yes, that's a difficult one to answer of course, because we have to actually get the drug filed for KMT2A and then we'll have to see what that timing looks like. But it's in -- I would say it's relatively close proximity.
Okay. Sorry. And that, that, that would be in close proximity in around the approval of KMT2A.
To the best of our understanding, it'll be sometime -- yes, both will happen in 2024. We don't think there'll be too far apart.
Brilliant. Thank you. Thanks so much. I'll get back into the queue.
Thanks, Peter.
The next question comes from Kalpit Patel with B. Riley Securities. Please go ahead.
Hi, this is William Wood on for Kalpit. Thank you for taking our questions. Just one from us. Quick follow-up actually on for your GVHD, when should we expect alignment on what dose or doses will be filed for axatilimab and strategically, do you think it's best to file for just one dose or is there an advantage for multiple dosing regimens on the label?
Thank you, William. Let me ask Neil to please comment on that on both of your questions.
So obviously, the agreement and as I -- well, let me just start by saying as I mentioned, we're currently conducting additional analyses to assess the benefit risk across all three doses. As you've seen the efficacy that we've observed at 0.3 milligrams and 1 milligram are pretty similar. The safety profile of the 0.3 mg/kg dose is excellent. We can't comment on which dose we would file or whether we would file one or two doses because we're in that has to be discussed with the agency.
I think that our objective would be to file the optimal dose as the recommended dose, but as the potential recommended dose. But that's -- that would be subject to discussion between well, actually insight will be leading the regulatory efforts between us insight and the FDA.
Thank you for that color. That's all I have.
Yes. I was just going to ask, was there a second part of your question?
No. That's it. I appreciate it. Thank you, Mike.
Okay. Well, thank you.
Thank you.
Next question comes from Justin Zelin with BTIG. Please go ahead.
Hi, thanks for taking the questions and congrats on the progress here. Maybe just a clarification question just on Michael's earlier one, just about the AUGMENT-101 duration of response. So when we see that data, we should assume that's inclusive of patients who have gone on transplant, is that correct? It's not going to be broken out by whether they've received transplant or not. Is that correct?
Justin thanks for the question. It's probably a little early to say how we will present that data per se. I mean, but I would say that the patients who we're looking at the overall patient experience and that will include patients that have gone on to transplant. And so I would expect that if we're reporting duration, we would include that calcul -- those patients in the calculation as well. So I'm just I mean maybe a little bit speculating. I haven't -- in this remark, I haven't said exactly that will be -- what we'll be breaking out. I'm just saying that if we are including those patients in the trial, then naturally they would be included in the duration assessment.
Got it. Okay. That makes sense to me. And naturally, the maintenance setting here is the large market. I'm just curious if you've talked about when you might see data either from the INTERCEPT study or the seven plus three combination study in the maintenance setting, or if it's too early to say that.
Yes. I think it is a little early to say we're just going to get the seven plus three trial up and running before the end of this year. And INTERCEPT is a cooperative group trial, which is ongoing. And I think we had said for the beginning that would take a little bit of time, so just a little early. We'll probably have more to say in 20 -- early in the year in 2024, how things are progressing and we will try to put a little finer detail around that.
That makes sense to me. And congrats also on the very positive axatilimab data. Just curious if you could comment on the subcutaneous formulation if you have any updates there or when we might see that formulation being ready for clinical studies.
Yes. Thanks for the follow-up. The SubQ is progressing nicely. I think the both Insight and Syndax are working in tandem to bring that forward and are progressing. We haven't put a timeline around that just yet. Again, stay tuned as we get a little bit closer here, but yes, it's a nice potential option that we think we could bring alongside the file dose or doses that we take forward.
Great. Well, thanks for taking my questions. Congrats once again. I'm looking forward to the data.
Thank you, Justin. Really appreciate it.
The next question comes from George Farmer with Scotiabank. Please go ahead.
Hi, good afternoon. It’s Chloe [ph] on for George Farmer. Just two from us. The first on AML. So giving you data so far, I'd like to know about competitors data in AML as well. Can you speak to your level of confidence about penetrating and dominating both the KMT2Ar and an NPM1 of AML assuming approval and/or do you think you're more positioned to come in higher market share ones the set versus the other? And your reasoning behind that. And the second question is on axatilimab just your comments on what your contribution will be to the commercial effort along with Insight.
Great. Thank you so much for the questions. So first of all, look, I think what's apparent to us at least, and I think to many is that we will be the first drug approved in this space first menin inhibitor approved for AML and ALL patients. And the first indication will be KMT2A and I think we'll -- we believe we'll be first to market there and best-in-class. And I think that extends to NPM1 as well. I think we believe we'll reach the market first and have a best-in-class profile.
So from our vantage point, we see execution in front of us and feel very confident that we can get this done based on the data that we presented thus far. And I would align the fact that it robust data set in Phase 1 presented at ASH really I think sets us up very nicely to be a top contender and really lead the field. So that's how we feel. And we -- as of today, there's really not a lot of data out there that would suggest otherwise, so that's revumenib.
With axatilimab, our set up with and our arrangement with Insight is that we can participate, we have an option to participate in the commercialization of axatilimab up to 30% of the commercial effort. And that's an election that we will be making over the next quarter or two. So it's relatively soon, we'll make that election. It's an interesting setup commercially for us because as we talked about, there are -- we have two drugs coming to market at pretty much the same time. And it's a very similar overlapping call point. So physicians that will be calling on could be detailed with both drugs. So it's for a small company our size, it provides a very meaningful commercial opportunity, which we would look to take advantage of. So again, that's an election that we'll make in the next few quarters, but it does provide an advantage to us and it was done with purpose in doing this transaction with Insight.
Got it. Thank you. And just a quick follow-up what are some of these the key drivers behind the decisions? So what are some of the factors there that you'll take into account?
What are the key drivers to consider for commercial launch for us? Why would -- did I hear your question correctly?
Yes. So some of the key factors you'll take into account before making that election decision.
Yes. Thanks for that. Well, I think it comes down to there's no difference in the economics for us. It's a 50:50 profit split for us in the U.S. So we are contributing to the cost of commercialization regardless of whether we provide reps or not. As I mentioned, it is a -- an efficient setup for us in that we have both products and sales reps will be calling on the same physicians for both products.
So there's overlap there. So we wanted to ensure that that was indeed the case and we have and so certainly, the efficiency of which we can deploy our reps and how meaningful that will be for us in our commercial effort for revumenib as well. That, that, that is kind of what we're thinking about. It is probably not as complicated as one would think. It's pretty straightforward. So I'll just leave it there.
This does conclude today's question-and-answer session. I will now turn the call back over to Michael Metzger for any additional remarks.
Great. Well, thank you, operator, and thanks for all the questions today. We look forward to seeing many of you at the upcoming conferences in August and into September and look forward to the data disclosure, which we talk about today for revumenib in the near future. Thank you very much. Have a great evening.
This does conclude today's program. Thank you for your participation. You may disconnect at any time.