Syndax Pharmaceuticals - Q2 2023
August 3, 2023
Transcript
Operator (participant)
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 Clary, Head of Investor Relations at Syndax Pharmaceuticals. Please go ahead.
Sharon Clary (Head of Investor Relations)
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 Clary, and with me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer, Dr. Neil Gallagher, President and Head of R&D, and Keith Goldan, Chief Financial Officer. Also joining us on the call today for question and answer session are Dr. Peter Ordentlich, Chief Scientific Officer, and Dr. Anjali Ganguli, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the investor page of the company's website. You can now turn to our forward-looking statements on slide two.
Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements made represent our views as of today, August 3, 2023, only. A report of this call will be available, excuse me, 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.
Michael Metzger (CEO)
Thank you, Sharon. 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 data set at a future medical meeting. As you can see on slide three, we are looking forward to reporting data from the KMT2A population of the AUGMENT-101 trial of revumenib in acute leukemias 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 mid-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 30th. This amount of cash not only funds our planned commercial launches and the trials we have laid out on slide three, 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, 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 four 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 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 II 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 aged 1 month or older. The primary endpoint of each of these is the % 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 they are at a high risk of relapse. As a reminder, in the phase I 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 five, 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 at, 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 retreatment 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 six, 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/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 I BEAT-AML umbrella trial. Revumenib is being combined with Venclexa and azacitidine to treat newly diagnosed AML patients who are unfit for induction chemotherapy as part of our collaboration with the Leukemia & 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 an all-oral regimen, revumenib with Venclexta and ANCHOVY, 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 seven + 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 seven, 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. 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, the menin-MLL1 interaction in beta-catenin-driven tumors. To that end, we are enrolling a proof-of-concept, signal-seeking phase I clinical trial in metastatic colorectal cancer.
The trial is proceeding through the dose escalation phase. 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?
Neil Gallagher (President and Head of R&D)
Thank you, Michael. Moving now to axatilimab, a monoclonal antibody targeting the CSF-1R, beginning on slide eight. 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 7, Day 1, using the 2014 NIH consensus criteria for chronic GVHD. Patients were stratified at baseline based on prior exposure to ibrutinib, ruxolitinib, or venetoclax, as well as disease severity, and then treated until 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 groups, each investigating a different dose of axatilimab. These were 0.3 mg/kg or 1 mg/kg every two weeks, and 3 mg/kg 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 while maintaining robust efficacy.
The 0.3 mg/kg 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 I trial, where responses were observed in patients who received 0.15 and 0.5 mg/kg every two weeks. This is also supported by PK/PD data from a previous axatilimab phase I trial in healthy volunteers. After 6 months on trial, patients at the 0.3 mg/kg and 1 mg/kg doses had the option to switch to a dose-proportional, once-monthly regimen. Turning to slide nine. 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 mg/kg every 2, 67% in patients treated at 1 mg/kg every two weeks, and 50% in patients treated at 3 mg/kg 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 mg/kg dose level. As I just mentioned, at the 0.3mg/kg dose, dose level, the response rate by cycle 7, day 1, was 74%. Moreover, the observed responses were durable, with a median duration of response not yet reached at the time of data cutoff.
60% of patients who responded to axatilimab were still responding at 1 year. The responses were accompanied by a reduction in symptom burden, as measured by the Modified Lee 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, the pivotal trial of Revuforj, that targeted a similar population of patients with chronic GVHD that received two or more prior lines of therapy.
As you can see, there were meaningful differences in patient populations between the Revuforj 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 just 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.
Michael Metzger (CEO)
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 are 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 Revuforj 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 will now turn the call over to Keith to review our financial results. Keith?
Keith Goldan (CFO)
Thank you, Michael. Let me take a few minutes to discuss our financial results for the quarter ended June 30th, 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 in 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-$43 million, and total operating expenses to be $57 million-$62 million. For the full year 2023, the company continues to expect research and development expenses to be $160 million-$175 million, and total operating expenses to be $225 million-$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.
Michael Metzger (CEO)
Yeah. 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, and 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.
I'd also like to thank our committed long-term investors who continue to share in our vision and support us in building Syndax. With that, I'd like to open the call for questions. Operator?
Operator (participant)
At this time, if you would like to ask a question, please press star one on your touchtone phone. You may remove yourself from the queue at any time by pressing star two. Once again, that is star one to ask a question. We will pause for a moment to allow questions to queue. The first question today comes from Phil Nadeau with TD Cowen. Please go ahead.
Phil Nadeau (Managing Director of Health Care and Biotechnology Research Analyst)
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, 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?
Michael Metzger (CEO)
Yeah, thanks, Phil, for the, for the first question. We have not disclosed the lower bound, nor the target rates or the statistics. We haven't, 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. 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, you know, better than that, somewhere between 20% and 30%. We haven't given specific guidance on the lower bound and what the target is for the trial.
Phil Nadeau (Managing Director of Health Care and Biotechnology Research Analyst)
Great. Second question on the pivotal study. I think most investors are gonna 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, fair assumption that what you show in KMT2A is likely to be repeated in NPM1?
Michael Metzger (CEO)
Thanks for the question, Phil. Yeah, look, I think our, our phase I experience was that the, the data looked the same, you know, very similar. The point estimate was 27% at the RP2D. That rationale would make some sense to us. Sure, I think it's, it's reasonable to think that they would be, you know, roughly the same.
Phil Nadeau (Managing Director of Health Care and Biotechnology Research Analyst)
Great. Last question from us. On BEAT AML, the press release says that Syndax is gonna receive the safety data... in the recommended phase II 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?
Michael Metzger (CEO)
Yeah, thanks for that question. The BEAT AML trial is obviously a cooperative group trial, and so, we have, you know, close collaboration with that group. We have the expectation that, you know, we'll have some information related to safety and the RP2D before the end of the year, and we'll look for a way to communicate that appropriately, but we haven't committed to what, what venue that'll be done at.
Phil Nadeau (Managing Director of Health Care and Biotechnology Research Analyst)
Great. Thanks for taking our questions.
Michael Metzger (CEO)
Thank you, Phil.
Operator (participant)
The next question comes from Anupam Rama with JPMorgan. Please go ahead.
Anupam Rama (Managing Director and Senior Equity Analyst)
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. As we think about AGAVE-201 data, the full update later this year, can you remind us of what additional analyses you're thinking about presenting later in the year that could provide some insights on the emerging profile of axatilimab? 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.
Michael Metzger (CEO)
Great. Thanks, Anupam. Maybe the first question related to the AGAVE-201 trial and the full update, maybe I'll ask Neil to cover that, please.
Neil Gallagher (President and Head of R&D)
Sure. Thanks, Michael, and thanks for the question. We have not as yet disclosed, for instance, response rates by disease, by organ class affected. We haven't, 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 and the high overall response rates, that, that there will be anything concerning in there, but we haven't, we haven't disclosed yet. You know, our, our plan, as I mentioned, we haven't performed the exposure response analyses as yet, and we expect to be able to do all of that at a meeting in the future.On top of that, you know, we will disclose whatever, whatever data we have to hand that, that could be of use to the prescribing community, obviously, in discussion with our, with our partner, Info.
Michael Metzger (CEO)
Great. Maybe, the second question, Anupam, was related to market potential and what, what, you know, the market may be missing relative to what we've presented thus far, and maybe I'll ask Anjali to, to address that.
Anjali Ganguli (Chief Business Officer)
Sure. Thanks, Michael. Thanks, Anupam. you know, 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 to have for a label for axatilimab. 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%-30% had prior Revuforj and ibrutinib exposure.
Despite enrolling a population of very severe chronic GVHD, with extensive times in diagnosis and multiple prior therapies, the drug was extremely tolerable, especially at the 0.3 mg per kg dose, with a very low rate of discontinuations. The effects are meaningful and, and durable, and we know physicians are excited about this profile and eager to have axatilimab as an option for their patients. You know, the fulsome data set from AGAVE, as, as Neil just talked about, is likely to provide you know, more exact differentiation for axatilimab. 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.
As Michael said, we know its profile as an 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, and generating that data over time, but even today, we think there's, there's going to be a significant value that axatilimab brings to these patients.
Michael Metzger (CEO)
Anything else, Anupam?
Anupam Rama (Managing Director and Senior Equity Analyst)
Thanks so much for taking our questions.
Michael Metzger (CEO)
Yeah, thank you.
Operator (participant)
The next question comes from Yigal Nochomovits with Citi. Please go ahead.
Ashiq Mubarack (Assistant VP of Biotechnology Equity Research)
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, you know, we'll get the CR/CRh data. 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.
Michael Metzger (CEO)
Yeah, thanks for the question. Look, I think our, 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 full profile of the drug. There will be information that is not included in the top line. I think, you know, primary endpoint, being CRH and duration, are likely to be part of that release. I think beyond that, you know, it's, it's, it's hard to say at this point what, what will be provided, but we know we, we, we're pretty, pretty, you know, attuned to what people are looking to see, and we'll hope to provide that as much as possible in the top line.
Ashiq Mubarack (Assistant VP of Biotechnology Equity Research)
Okay, I, 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, you know, 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 about the lower end of the range. Thanks.
Michael Metzger (CEO)
Yeah, thanks for the question. I'll ask Keith to address that please.
Keith Goldan (CFO)
Yeah, regarding the, the second quarter, Yigal... I'm sorry, not Yigal. Regarding the second quarter, there's remarks in the, in the press release and in the Q that spoke to some lower spending on manufacturing, it's called CMC. That was primarily a timing issue. We, 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. You know, with respect to your question on full year, you know, I appreciate that we did come in in the quarter, under. Yeah, I would just look to us reaffirming the full year guidance, and not gonna make further comments for the for R&D and OpEx beyond that.
Ashiq Mubarack (Assistant VP of Biotechnology Equity Research)
Okay, great. That's very helpful. Thanks very much.
Keith Goldan (CFO)
Thanks for the questions.
Michael Metzger (CEO)
Thank you.
Operator (participant)
The next question comes from Brad Canino with Stifel. Please go ahead.
Brad Canino (Equity Research Analyst for Small to Mid Cap Biotechnology)
Good afternoon. You know, as you talked about in your remarks, the REvu restarts after transplant and that post-transplant durability number will be important information, and I think it's gonna take time to gather those data after the top-line release this quarter. 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.
Michael Metzger (CEO)
Yeah. Brad, thanks for the question. Let me ask Anjali to comment on that question.
Anjali Ganguli (Chief Business Officer)
Yeah, sure. Thanks, Brad. I think the difference between the... in the relapse 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, have the opportunity to go back on therapy. I think that's where where our molecule, revumenib, is bringing a very differentiated profile and opportunity to extend treatment duration and, and really prolong benefit for these patients.
Brad Canino (Equity Research Analyst for Small to Mid Cap Biotechnology)
Okay. Maybe just a, 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? Does it imply that you believe the focus of the data, given it's a phase I, should be on safety?
Michael Metzger (CEO)
Yeah, Brad, I think it's the latter. Thanks for the question. I think we, what we were trying to... This is a phase I dose escalation trial, right? The focus is always on safety. We're pretty consistent in saying so, in phase I, and, and obviously, we're trying, the goal is to get through dose escalation to get to an RP2D, and we hope to inform on, on that experience, before the end of the year.
Brad Canino (Equity Research Analyst for Small to Mid Cap Biotechnology)
Yeah. Okay. I, I do have several investor conversations that reference, like, the FLT3 and IDH triplets, where those phase I results were 90% plus CRs, high rates of MRD negativity. I wanna know from you, are these the right precedent comps to think about for your triplet at this stage? What other caveats would you suggest we think about as we try to compare those data?
Anjali Ganguli (Chief Business Officer)
Yeah, I think, Brad, you're, you're I mean, it's going to be tricky with a small patient population when you're adding on to an already effective therapy to, to really see meaningful differences, above and beyond. You know, we obviously think there's going to be a benefit from the triplet, but, whether it, you know, plays out exactly where the enhancements are in a, you know, a handful of patients, I think, is, is what we're waiting to see.
Michael Metzger (CEO)
Yeah, I think just to add on to Anjali, what Anjali was saying, I think we need to caution everyone to, you know, again, these are late-line patients, or sorry, they're, they are early patients, but they're not a lot of them, so we're not, we're not gonna assume too much on the efficacy side. I think this, again, is we'll see, 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.
Brad Canino (Equity Research Analyst for Small to Mid Cap Biotechnology)
Okay. Appreciate it. Thank you.
Michael Metzger (CEO)
Great. Thanks, Brad.
Operator (participant)
The next question comes from Michael Schmidt with Guggenheim. Please go ahead.
Michael Schmidt (Senior Biotech Analyst)
Hey, guys, thanks for taking my questions. I had a few follow-ups along the same lines. In AUGMENT-101, when the KMT2A cohort, in the pivotal cohort, is the percentage of patients receiving transplant and subsequent maintenance similar to that in your phase I experience? You know, I'm just thinking about REPO in terms of the DOR in the current study.
Michael Metzger (CEO)
Right. Thanks for the question, Michael. Just a reminder, in the phase I, we didn't have patients going back on, on drug post-transplant. That was not part of the protocol. One of the major changes between phase I and phase II portion of the AUGMENT trial is that on, in phase II, we were able to have patients go back on treatment post-engraftment. That is, that is the, you know, a major change. And obviously, when you measure duration of therapy, median duration will account for the fact that patients go you're, you're measuring how long patients stay on, on therapy until relapse. It's, you know, that's really the measure, and that measure includes whether or not they go to transplant.
They're not censored at the time of transplant, they continue, it's as if they're on one line of therapy. 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, and, 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 stay on treatment, and we'll track those as well. There'll be, you know, different experiences in the phase II, all, you know, I would say, some of those patients enabled by the fact that they're able to go back on treatment and, and be treated as maintenance.
Michael Schmidt (Senior Biotech Analyst)
Got it. Understood. Thanks. Then regarding the, you know, the question, the regulatory bar, the efficacy hurdle, my question is, is the efficacy hurdle in relapsed refractory AML in the NPM1 subset different than in the KMT2A subset, given some overlap there with FLT3 and IDH mutations where other treatments are available?
Michael Metzger (CEO)
Yeah, thanks for the question, Michael. I think, 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, you know, with fourth, fifth line patients, once they get to that really refractory stage of their disease, our view is that, you know, the hurdle rate for approval is likely to be similar. Now, you know, 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. That should give you some, some understanding that our, our statistics are set up in the same way.Again, I think regulatory precedent in AML is one thing, and you can maybe deduce, you know, something from the construction of our trials as well.
Michael Schmidt (Senior Biotech Analyst)
Okay, super. Then lastly, on the BEAT AML, safety data later this year or early next, I guess, you know, if we see the safety data, what, what, what frequency of adverse events or w- what, you know, what type of safety profile i- would you view as acceptable? Is there a particular rate of thrombocytopenia, for example, that, you know, that you would view as kind of the, the upper, the upper end of, what's acceptable in order to advance, i- in this constellation into a registration study?
Michael Metzger (CEO)
Yeah, thank, thanks for that last question. I, I would, I would just say this at this stage, before we have data and before we've actually disclosed anything, you know, we'll, we'll be looking at the totality of the data, and obviously, the safety and tolerability is gonna 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, should, you know, combine nicely, and so, we'll have to see what the overall profile looks like at the time that we present the data.
Michael Schmidt (Senior Biotech Analyst)
Okay, great. Thank you so much.
Michael Metzger (CEO)
Thank you, Michael.
Operator (participant)
The next question comes from Peter Lawson with Barclays. Please go ahead.
Peter Lawson (US Biotech Equity Analyst and Managing Director)
Great. Thank you so much. Just to, I guess, follow up around the GVHD side of things, just when we should expect the, the full data set there, if that's kind of an ASH event, and if there's... kind of what we should be focused on around that data set, if it's the, kind of the differentiation, kind of starts emerging, between you and Revuforj?
Michael Metzger (CEO)
Yeah. Yeah, thank you, Peter. Thanks for the question. Without giving away exact meetings, 'cause we tend not-- we haven't disclosed what exact, what meeting that data set 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. Maybe I'll ask Neil to follow up on the question about additional information and differentiation.
Neil Gallagher (President and Head of R&D)
Thanks for the question. Well, you know, I already pointed to the fact that we would, we haven't yet disclosed, for instance, responses across affected disease organ classes. I would anticipate that when we get to presenting data at a medical meeting, that those data will be included. You know, just, just to recap, and as we alluded to during the prepared remarks in the presentation, the, the population that was included in the AGAVE-201 study was, you know, really heavily more severe and more heavily pretreated than those patients included in, in, in prior pivotal studies with the approved agents. I won't reiterate all, all, all of the, all of the data points, but in terms of disease severity, as I've mentioned, the number of prior therapies, the time from diagnosis.
Also I would point to, you know, the safety data that we've already disclosed, and in particular, the low rates of discontinuation, particularly at 0.3 mgs per kg Q2 weekly, where only six patients discontinued as a result of adverse events. I think you can, you know, expect, as I said, a more extensive data disclosure at that meeting. We'll make every effort with our partner, Incyte, to include all of the relevant information that could be helpful to you and the medical community on patients.
Peter Lawson (US Biotech Equity Analyst and Managing Director)
Great. Thank you. Then just on the NPM1 side of the story, kind of, when should we expect to see that data in, I guess, 2024? Is that kind of before or after a potential filing for the KMT2A, approval in AML?
Michael Metzger (CEO)
Yeah, thanks for the question, Peter. NPM1, our guidance is 2024. We haven't narrowed that at this point. In terms of... I'm sorry, what's the second part of your question?
Peter Lawson (US Biotech Equity Analyst and Managing Director)
Oh, if that kind of trying to narrow it down, actually, whether it, it comes before or after the, the potential filing of KMT2A.
Michael Metzger (CEO)
Right, of course. Yeah, that's a, that's a difficult one to answer, of course, because, you know, we have to actually get the drug, you know, filed for KMT2A, and then we'll have to see what that timing looks like. I would say it's relatively close proximity.
Peter Lawson (US Biotech Equity Analyst and Managing Director)
Okay. Sorry. That, that, that would be in close proximity in around the approval of, of KMT2A?
Michael Metzger (CEO)
To the best of our understanding, it'll be sometime... Yeah, both will happen in 2024. We don't think they'll be too far apart.
Peter Lawson (US Biotech Equity Analyst and Managing Director)
Brilliant. Thank you. Thanks so much. Okay, bye.
Michael Metzger (CEO)
Thank you. Thanks, Peter.
Operator (participant)
The next question comes from Kalpit Patel with B. Riley Securities. Please go ahead.
William Wood (Biotech Equity Research Analyst)
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? 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?
Michael Metzger (CEO)
Thank you, William. Let me ask Neil to please comment on that, on both of your questions.
Neil Gallagher (President and Head of R&D)
Obviously, the, the agreement and well, let me, let me just start by saying, as I mentioned, we're currently conducting additional analyses to assess the benefit risk across all three doses. You know, as you've seen, the efficacy that we've observed at 0.3 mg and 1 mg are pretty similar. The safety profile of the 0.3 mg per 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 to have to discuss with the, with the agency.I think that our objective would be to file the optimal dose as, as the recommended dose, but as the potential recommended dose, but that will be subject to discussions between. Well, actually, Insight will be leading the, the, the regulatory efforts between us, Insight and, and the FDA.
William Wood (Biotech Equity Research Analyst)
Thank you for that clarity. That's all.
Michael Metzger (CEO)
William? Yeah. I was just going to ask, is there a second part of your question?
William Wood (Biotech Equity Research Analyst)
No, that's it. I appreciate it.
Michael Metzger (CEO)
Thank you much.
William Wood (Biotech Equity Research Analyst)
Well, thank you.
Michael Metzger (CEO)
Thank you.
Operator (participant)
The next question comes from Justin Zelin with BTIG. Please go ahead.
Justin Zelin (Biotechnology Research Analyst)
Hi, thanks for taking the questions, congrats on the progress here. Maybe just a clarification question just on Michael's earlier one, just about the AUGMENT-101, duration of response. 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?
Michael Metzger (CEO)
Justin, thanks for the question. It's probably a little early to say how we will present that data per se, but I would, 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. So I would expect that if we are reporting duration, we would include you know, those patients in the calculation as well. I'm just maybe a little bit speculating. I haven't, you know, in, in this remark, I haven't said exactly that 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.
Justin Zelin (Biotechnology Research Analyst)
Got it. Okay, that makes sense to me. You know, naturally, the, the, the maintenance setting here is a, is a large market. I'm just curious if you, if you've talked about when we 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?
Michael Metzger (CEO)
Yeah, I think, 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. INTERCEPT is a, you know, a cooperative group trial, which is, ongoing, and I think we had said from the beginning that would take a little bit of time. Just a little early. We'll probably have more to say in 20, you know, early in the year, in 2024, how things are progressing, and we'll try to put a little finer, finer detail around that.
Justin Zelin (Biotechnology Research Analyst)
That makes sense to me. congrats also on the, the, the very positive axatilimab data. Just curious if you could comment on the subcutaneous formulation, if, if you have any updates there or, you know, when we might see that formulation being ready for, for clinical studies?
Michael Metzger (CEO)
Yeah, thanks for the follow-up. The subcu is progressing nicely. I think the, you know, 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. Yeah, it's a nice potential option that we think we could bring, bring alongside the, the final dose or doses that we take forward.
Justin Zelin (Biotechnology Research Analyst)
Great. Well, thanks for taking my questions. Congrats once again. I'm looking forward to the data.
Michael Metzger (CEO)
Thank you, Justin. Really appreciate it.
Operator (participant)
The next question comes from George Farmer with Scotiabank. Please go ahead.
Chloe Young (Equity Research Associate)
Hi, good afternoon. This is Chloe Young for George Farmer. Just two from us. The first on AML. Given your data so far and what you know about competitors' data in AML as well, can you speak to your level of confidence about penetrating and dominating both the KMT2AR and then NPM1 subset of AML, assuming approval, or do you think you're more positioned to come in at a higher market share in one subset versus the other, and your reasoning behind that? The second question is on axatilimab. Just your comments on what your contribution will be to the commercial effort along with Insight.
Michael Metzger (CEO)
Great. Thank you so much for the for the questions. First of all, look, I think what's apparent to us at least, and I think m- to many, is that we will be the first drug approved, you know, in this space, first menin inhibitor approved for AML and ALL patients. You know, the first indication will be KMT2A, and I, I think we, we believe will 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. From our vantage point, we see execution in front of us and, and feel very confident that we can get this done based on the data that we've presented thus far.
I would underline the fact that a, you know, robust data set in phase I presented at ASH, really, I think, sets us up very nicely to be a, to be a, you know, top contender and, and really lead the field. That's, that's how we feel, and we, you know, we-- as, as of today, there's really not a lot of data out there that would suggest otherwise. That's, that's rebumenib. With axatilimab, our setup with, our arrangement with Insight is that we can participate, we have an option to participate in the commercialization of, 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. It's, you know, relatively soon we'll, we'll make that election.
It's a, you know, interesting setup commercially for us because as, as we talked about, we have two drugs coming to market at pretty much the same time. It's a very similar overlapping call point. Physicians that we'll be calling on could be detailed with both drugs. It's a, you know, for a small company our size, it provides a very meaningful commercial opportunity, which, you know, we would look to take advantage of. 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.
Chloe Young (Equity Research Associate)
Got it. Thank you. Just a quick follow-up. What are some of these, the, the key drivers behind, behind the decision? What are some of the factors there that you'll take into account?
Michael Metzger (CEO)
Oh, what are the key drivers to consider for commercial launch for us? Did I hear your question?
Chloe Young (Equity Research Associate)
for that.
Michael Metzger (CEO)
Maybe-
Chloe Young (Equity Research Associate)
Yeah. some of the key factors you'll take into account before making that election decision.
Michael Metzger (CEO)
Thanks for that. Well, I think it, it comes down to, you know, there's no difference in the economics for us. It's a 50/50 profit split for us in the U.S. We are contributing to the cost of commercialization, regardless of whether we provide reps or not. As I mentioned, it, it, it is an efficient setup for us in that we have both products, and, you know, sales reps will be calling on the same physicians for both products, so there's overlap there. We, we wanted to, you know, ensure that that was indeed the case, and we have.
Certainly the efficiency at 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's probably not as complicated as one would think. It's pretty straightforward, so I'll just leave it there.
Chloe Young (Equity Research Associate)
Got it. Thank you so much.
Michael Metzger (CEO)
Thank you.
Operator (participant)
This does conclude today's question and answer session. I will now turn the call back over to Michael Metzger for any additional remarks.
Michael Metzger (CEO)
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, and have a great evening.
Operator (participant)
This does conclude today's program. Thank you for your participation. You may disconnect at any time.