Syndax Pharmaceuticals Inc Q2 FY2023 Earnings Call

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 for joining us today for a review of Syndax's second quarter 2023 financial and operating results. I'm Sharon Klahre, and with me today are Michael Metzger, Chief Executive Officer; Dr. Neil Gallagher, President and Head of R&D; and Keith Goldan, Chief Financial Officer. We also have Dr. Peter Ordentlich, Chief Scientific Officer; and Dr. Anjali Ganguli, Chief Business Officer participating in the question-and-answer session. This call includes a slide deck posted on the Investors page of our website. Please refer to our forward-looking statements on Slide 2. I want to remind you that any non-historical statements made during this call are considered forward-looking statements under the Private Securities Litigation Reform Act of 1995. Actual results may differ significantly due to several important factors discussed in the Risk Factors section of our most recent Quarterly Report on Form 10-Q, as well as other filings with the SEC. The forward-looking statements represent our views as of today, August 3, 2023. A replay of this call will be available on the Company's website, www.syndax.com after the call concludes. I will now 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 in executing our milestones and corporate priorities, which set 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 started off the third quarter in a strong 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 shown on Slide 3, we are eager to report data from the KMT2A population of the AUGMENT-101 trial of revumenib in acute leukemia later this quarter. Additionally, we expect to have data from several of our trials of revumenib by year-end, which we believe could enhance its value proposition and support its best-in-class profile. Once we have pivotal data from both revumenib and axatilimab, Syndax will be uniquely positioned as a small-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 cash not only supports our planned commercial launches and the trials outlined on Slide 3 but also allows us to expand beyond our core registration indications and selectively pursue business development opportunities. We continue to assess earlier stage targeted oncology compounds to enhance our pipeline, but as we have previously communicated, our criteria for completing a transaction are high, as any new opportunity must be differentiated and create substantial future value to align with our long-term corporate strategy. Now, let's turn to Slide 4 to discuss 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 still expect to report data from KMT2A rearranged acute leukemia patients in the AUGMENT-101 pivotal trial in the third quarter of this year, which could provide 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 enrolled independently. These populations include KMT2A rearranged ALL, KMT2A rearranged AML, and NPM1 mutant AML, with each trial enrolling patients aged one month or older. The primary endpoint for each 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 after successful engraftment, which could be an important maintenance option for these patients, given their high risk of relapse. As a reminder, in the Phase 1 experience, some patients have remained on treatment and in response for nearly two years, which is possible due to revumenib's strong safety and tolerability profile. As previously reported in December 2022, we received breakthrough therapy designation for all KMT2A rearranged acute leukemia patients. In later discussions with the FDA, we agreed to pool a subset of data from the AML and ALL KMT2A cohorts into a single NDA filing aimed at treating 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 submit an NDA for this population by the end of 2023. Our aim for the top-line data disclosure is to provide sufficient data on efficacy and safety so that all stakeholders understand the drug profile while preserving enough details for 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, positions 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 a combination trial of an all-oral regimen, revumenib with VENCLEXTA and INQOVI, an oral hypomethylating agent in relapsed/refractory acute leukemia being led by Dr. Issa at MD Anderson Cancer Center. 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. 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, a 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 cohorts, 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 regimens were chosen to allow time for recovery of the macrophage population, thereby potentially minimizing adverse events while 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 had the option to switch to a dose proportional once monthly regimen. Turning to Slide 9, I want to reemphasize 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 the data cut. 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 the 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 underscore how impressive the AGAVE-201 trial results are and point to the significant value axatilimab could bring to patients if approved.

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. 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 theoretical 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 equivalents 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?

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 thank you for the question. We have not yet had the chance to share response rates based on disease or the affected organ graft. We also haven't released response rates determined by prior therapy, although we believe that given the extent of prior therapy and the high overall response rate, there should not be any significant concerns in the data we haven't revealed yet. As I mentioned, we have not conducted the exposure-response analysis at this point. We anticipate being able to present all of this information at a future meeting. Additionally, we will share any relevant data that could assist the prescribing community, in collaboration with our partner.

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. That was a population we enrolled in the AGAVE-201 trial and what we expect the label for axatilimab to be. 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, it provides 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. As Michael said, we know its profile and antibody enables safer combinability and can extend its promise to deliver disease-modifying effects to earlier patients. We'll be working on that trial and generating that data over time, but even today, we think there's going to be 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, 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. 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. Regarding the second quarter, the press release and the Q mentioned some lower spending on CMC, primarily due to timing issues. We indicated in the Q that this contributed to lower R&D expenses in the second quarter, leading us to be under guidance. With respect to your question about the full year, we did come in below expectations for the quarter, but I would like to reaffirm our full-year guidance and won't provide further comments on 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 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 question.

Thank you, Brad. In the relapsed/refractory setting, neither the IDH inhibitors nor the FLT3 inhibitors showed significant transplant rates, resulting in very few patients having the chance to re-enter treatment. Our molecule, revumenib, offers a unique profile and the potential to extend treatment duration and provide prolonged benefits 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 believe it's the latter. Thank you for your question. What we're addressing here is a Phase 1 dose escalation trial, where the primary focus is on safety. We have consistently stated this about Phase 1 trials, and our aim is to proceed through dose escalation to determine a recommended Phase 2 dose. We hope to provide insights on that experience before the year concludes.

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 believe, Brad, it's going to be challenging with a small patient population when you’re adding to an already effective therapy to really observe significant differences. We certainly expect some benefits from the triplet, but whether we can pinpoint exactly where the enhancements occur in a limited number of patients is what we're currently waiting to see.

Yes. I think just to add on to 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, 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. In the AUGMENT-101 study, specifically in the KMT2A cohort, is the percentage of patients receiving a transplant and subsequent maintenance similar to what we observed in your Phase 1 study? I am considering this in relation to the duration of response in the pivotal study.

Thank you for the question, Michael. In Phase 1, we did not have patients returning to treatment after their transplant as it wasn't part of the protocol. A significant change between Phase 1 and Phase 2 of the AUGMENT trial is that in Phase 2, patients are allowed to resume treatment after engraftment. This change impacts how we measure the duration of therapy, which tracks how long patients stay on therapy until they relapse. This measurement includes whether or not they undergo transplant, so patients are not excluded from the measurement at that time; they continue as if on a single line of therapy. Some patients will receive therapy but not undergo transplant and then progress, while others will have the transplant and continue treatment without needing to retreat with revumenib. Some will have the transplant and then be retreated with revumenib, continuing their treatment, and we'll track all these experiences in Phase 2. The ability for some patients to return to treatment and receive maintenance therapy is an important aspect of this phase.

Got it. Understood. Thanks. Regarding the question about the regulatory bar, is the efficacy hurdle for relapsed/refractory AML in the NPM1 subset different from that in the KMT2A subset, considering the overlap with FLT3 and IDH mutations in available treatments?

Yes. Thanks for the question, Michael. There are currently no drugs approved specifically for either NPM1 or KMT2A in the relapsed/refractory setting. I would like to note that for patients in the fourth or fifth line of treatment, once they reach a very refractory stage of their disease, we believe the approval criteria will likely remain similar. While we haven't shared the detailed statistics of our trial, each of the individual cohorts has the same number of patients, which should give you some insight into how our statistics are structured. In summary, regulatory precedents in AML are one aspect to consider, along with the design of our trials.

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 you would view as the upper end of what's acceptable in order to advance in this constellation into a 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.

Thank you, Peter, for your question. While I can't disclose the exact meeting where the dataset will be presented, I can share that our goal is to have it ready before the end of the year. I believe that timeline gives a hint about when to expect it. I’ll also ask Neil to address the question regarding additional information and how we differentiate ourselves.

Thank you for the question. I previously mentioned that we have not yet shared responses across the affected disease organ classes. I expect that when we present data at a medical meeting, this information will be included. To summarize, the population in the AGAVE-201 study was notably more severe and experienced more prior treatments than patients in earlier pivotal studies with approved agents. I won’t repeat all the data points, but regarding disease severity, the number of prior therapies, and time since diagnosis, I would also highlight the safety data we've disclosed, particularly the low rate of discontinuation at the 0.3 mg/kg Q2 weekly dosage, where only six patients discontinued due to adverse events. As I mentioned, you can look forward to a more comprehensive data disclosure at that meeting, and we will strive to work with our partner to include all pertinent information that could benefit both you and the medical community regarding patients.

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. Thank you for your question, Peter. Regarding NPM1, our guidance is for 2024, but we haven't specified that yet. Could you remind me of 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.

That's a challenging question to answer because we first need to get the drug filed for KMT2A and then assess the timing. However, I would say it's relatively close.

Okay. Sorry. And that would be in close proximity around the approval of KMT2A.

To the best of our understanding, it'll be sometime in 2024. We don't think they'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 on 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, we are 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 process 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 subject to the 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.

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?

Thank you for the question, Justin. It may be a bit early to determine how we will present that data specifically. However, I would mention that we are considering the overall patient experience, which includes patients who have undergone a transplant. Therefore, if we report duration, those patients would also be included in the calculation. I might be speculating a little here, and I haven't specified exactly what we will separate out, but if those patients are part of the trial, they would naturally 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 early 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 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 filed 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 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.

Thank you for the questions. First, it’s clear to us that we will be the first drug approved in this area, specifically the first menin inhibitor for AML and ALL patients. Our initial indication will be KMT2A, and we believe we will be first to market and best-in-class. This expectation extends to NPM1 as well, as we feel confident we will also reach the market first with a leading profile. Based on the data we’ve presented so far, we are optimistic about our execution and ability to achieve this. The strong Phase 1 data we shared at ASH places us in a favorable position to be a leading contender in the field. Currently, there isn’t much data suggesting otherwise, so that’s our outlook on revumenib. Regarding axatilimab, we have the opportunity to participate in its commercialization, potentially up to 30% of the market effort. We will decide on this option in the next quarter or two. This setup is strategically beneficial for us, especially since we have two drugs launching simultaneously, which will reach similar physician audiences. This presents a significant commercial opportunity for a company of our size, and we plan to leverage it. We’ll make our decision regarding this collaboration with Insight in the coming quarters.

Got it. Thank you. And just a quick follow-up on what are some of these key drivers behind the decisions? So what are some of the factors there that you'll take into account?

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 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 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 talked 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.