Good day, everyone, welcome to the Syndax first 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.
Thank you, operator. Welcome. Thank you all for joining us today for a review of Syndax's first quarter 2023 financial and operating results. I'm Sharon Klahre, and with me this afternoon to provide an update on the company's progress and to discuss financial results are Michael Metzger, Chief Executive Officer, Dr. Neil Gallagher, President and Head of R&D, and Keith Goldan, Chief Financial Officer. Also joining us on the call today for the question and answer session are Dr. Peter Ordentlich, Chief Scientific Officer, and Dr. Anjali Ganguli, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the investor page of the company's website. You can now turn to our forward-looking statements on slide two.
Before we begin, I would like to remind you that any statements made during 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 for 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, May 8, 2023, only. 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 it over to Michael Metzger, Chief Executive Officer of Syndax.
Thank you, Sharon, and thank you all for joining the webcast. I want to also welcome Dr. Neil Gallagher to the call today as our new President and Head of R&D. Neil is a highly accomplished oncology drug developer and his deep experience across all stages of drug development and strong track record of successful drug approvals will be instrumental in driving continued pipeline development and growth at Syndax.
You will hear from Neil later in the call. We also welcome Kevin McManus to the company as our new Chief People Officer. We look forward to benefiting from his extensive experience and vision in building our organization and culture. Turning to slide three, where we provide a high-level summary of our current corporate priorities. Throughout the first quarter, we continued to execute on our clinical and corporate strategy.
We are confident in our ability to deliver pivotal readouts and registration filings for our two lead drug candidates later this year. We are on the cusp of realizing the potential of our science by delivering treatments that provide critical benefit to patients where there is significant unmet medical need. Diving into revumenib, our highly selective menin inhibitor.
Our pivotal phase II AUGMENT-101 trial evaluating revumenib in patients with relapsed refractory NPM1-mutant or KMT2A-rearranged acute leukemia is progressing well. We 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.
We have several additional trials ongoing designed to expand the potential of revumenib beyond use as a monotherapy agent in patients with relapsed/refractory acute leukemias, including combinations with standard of care regimens to treat these forms of acute leukemia. We expect to have initial data from several of them by the year-end.
I will provide details on each of these trials later in the call. Moving to axatilimab, our antibody against CSF1R. We remain on track to report top-line data in mid-2023 from the pivotal phase II AGAVE-201 trial evaluating axatilimab in patients with chronic Graft-Versus-Host Disease, or cGVHD. Plan to submit a BLA filing by the end of 2023. With Incyte, we have the support of a strong pharmaceutical partner to help us advance the development of axatilimab and successfully commercialize once approved.
Other trials that we expect to initiate this year include a phase I , II combination trial of axatilimab and Jakafi in cGVHD led by our partner Incyte, as well as a phase II trial of axatilimab in idiopathic pulmonary fibrosis, or IPF, that will be led by Syndax. As we prepare to become a commercial stage biopharmaceutical company delivering two best-in-class products to patients in areas of high unmet medical need, we continue to take a disciplined and thoughtful approach to building our organization with highly experienced and talented people.
We are well-funded with $449 million in cash as of March 31st. Our cash balance enables us to expand beyond our core registration indications and provides us flexibility to selectively pursue business development opportunities. As part of that effort, we continue to evaluate earlier-stage targeted oncology compounds for potential in-licensing.
We believe that we have sufficient resources to acquire new early-stage assets that have the potential to become high-value differentiated drugs, we have, as we have conveyed, a high bar for doing so, as any compound would need to complement our current pipeline and align with our long-term corporate strategy.
Let's now turn to slide four. I'll provide further details on the revumenib program. 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. The primary endpoint of each 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 also have the opportunity to be retreated with revumenib in the phase II portion, which could be an important maintenance option for these patients given that they are at high risk of relapse. Based on the broad breakthrough therapy designation we received in December 2022 and conversations with regulators, we will pool 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 from this pooled population in the third quarter of this year and plan to file an NDA for the treatment of relapsed/refractory KMT2A acute leukemia in adult and pediatric patients by the end of 2023.
Separately, we continue to enroll relapsed/refractory NPM1-mutant AML patients and expect completion of enrollment of this cohort in the second half of 2023. I'm happy to report that in the first quarter, we completed the clinical pharmacology work that supports a recommended phase II dose in any patient eligible for revumenib.
We have determined the RP2D in patients who are not on a strong CYP3A4 inhibitor is 276 mg every 12 hours and now have agency agreement on including this dose in AUGMENT-101. This means that any patient can be treated with revumenib whether or not they are receiving concomitant CYP3A4 inhibitors. We would expect this dose to be incorporated into the revumenib label at the time of approval. Moving to slide five. We are excited to now have the phase I AUGMENT-101 data published in Nature.
The work lays out the biology of revumenib and provides a thorough review of the data. In these heavily pretreated patients who have received a median of four prior therapies, 30% of the efficacy-evaluable population experienced a CR/CRh with an impressive median duration of CR/CRh response of 9.1 months as of the data cut-off date.
The authors concluded that revumenib monotherapy was associated with encouraging clinical benefit, including deep molecular remissions and durable responses with minimal toxicities in this heavily pretreated patient population. Turning to slide six. Based on revumenib's compelling efficacy and safety profile, our clinical strategy is to expand beyond the relapsed or refractory setting into earlier settings and post-transplant maintenance, as well as explore the combination of revumenib with approved therapies.
We believe that revumenib could become the backbone of treatment for patients with KMT2AR and NPM1 mutant acute leukemias. By unlocking the full potential of revumenib, meaningful value would be added. There are currently no FDA-approved therapies targeting KMT2AR 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 mutant and KMT2AR acute leukemia patients across various settings. Of this significant unmet medical need, we are committed to bringing encouraging clinical benefits to even more patients. Here we highlight our ongoing trials of revumenib across the treatment landscape. Starting with the phase I BEAT AML umbrella trial.
As part of our collaboration with the Leukemia & Lymphoma Society, revumenib is being combined with venetoclax and azacitidine to treat newly diagnosed AML patients with an NPM1 mutant or KMT2A rearrangement who are unfit for induction chemotherapy. Revumenib is the first menin inhibitor to be included in this trial, which will assess safety as well as initial efficacy.
Enrollment is ongoing, we expect to report initial safety data from the trial by year-end 2023. Longer term, we expect that positive BEAT-AML trial results could lead to a phase II, III trial, which could serve as the basis for a future regulatory filing. We are also currently enrolling patients in the AUGMENT-102 trial designed to assess revumenib in combination with standard salvage chemotherapies for patients with relapsed or refractory NPM1 mutant or KMT2A rearranged acute leukemias.
We expect to reach a recommended phase II dose and report initial data from this trial in 2023. The INTERCEPT trial continues to enroll patients as part of the master clinical trial led by the Australasian Leukaemia & Lymphoma Group. The trial is a creative approach to treating patients early in their disease course, as it is focused on investigating novel therapies to target early relapse and clonal evolution as preemptive therapy in AML.
It is designed to explore the activity of revumenib, the first menin inhibitor to be included in this master trial, as monotherapy in patients with NPM1 mutant or KMT2A rearranged AML who have MRD positive disease following initial treatment, a group of patients at very high risk of relapse. Data from this trial could also provide additional support for use of revumenib in a maintenance setting.
We also plan to initiate a trial of revumenib in combination with standard of care intensive chemotherapy, known as 7+3, in the frontline setting in the second half of this year. Turning to slide seven. Beyond the market opportunity that we outlined here in acute leukemias, we are also exploring the use of revumenib as a treatment in solid tumors based on compelling preclinical science supporting the role of the menin-MLL1 interaction in β-catenin-driven tumors.
Enrollment is going well in our proof-of-concept signal-seeking phase I trial in metastatic colorectal cancer, and we expect to have initial data from this trial by year-end 2023. I'd like to turn the call over to Neil to briefly talk about chronic Graft-Versus-Host Disease and why we believe axatilimab, our potentially best-in-class monoclonal antibody therapy targeting the CSF1R, could benefit patients diagnosed with this disease. Neil?
Thank you, Michael. It's a pleasure to be part of this Syndax team and to showcase today why we're so excited about the AGAVE-201 top-line data that we expect to be able to share in the middle of the year. Turning to slide eight. There are approximately 14,000 patients living with chronic GVHD in the U.S. today.
While there are a number of recently approved agents that have brought benefit to patients suffering from the disease, there remains a significant unmet medical need across all lines of therapy. Following initial treatment with corticosteroids, patients are usually cycled through a variety of therapies, all of which are associated with high failure rates. Consequently, chronic GVHD remains a significant cause of morbidity and mortality among patients following transplant.
Based on the phase I, II data, which I will summarize shortly, we believe axatilimab provide a differentiated, effective, and practice-changing intervention for this underserved population. In slide nine, I would like to give some background on the disease pathology and the essential role that monocyte-derived macrophages have been shown to play in chronic GVHD.
The activation, proliferation, and survival of these macrophage populations is regulated through CSF1 receptor. Once localized to tissues where active disease is occurring, macrophages may take on either a pro-fibrotic or a pro-inflammatory role, depending on localized signaling factors. Therefore, attenuation of CSF1R receptor signaling using a blocking antibody such as axatilimab is expected to reduce circulating monocytes and derived macrophages and consequently reduce disease pathophysiology.
The differentiated mechanism of action of axatilimab, combining anti-fibrotic and anti-inflammatory activity, holds the promise to provide a new therapeutic option for chronic cGVHD patients, distinct from other approved therapies. The mechanism of CSF1R blockade also offers the potential for improving the outcomes of patients with chronic cGVHD when combined with other currently used therapies.
Based on encouraging preclinical data, we conducted a phase I, II trial of axatilimab in patients with chronic cGVHD. The results of the trial were published in the Journal of Clinical Oncology last fall and are summarized in slide 10. Patients included in the study were heavily pretreated with a median of four prior therapies. Among patients treated in the phase II portion of the trial, the overall response rate by cycle seven, day one was 82%, with a median time to response of four weeks.
At the time of data cutoff, the median duration of exposure to axatilimab was 38 weeks, and the median duration of response had not yet been reached. Importantly, clinical responses were accompanied by a reduction in chronic cGVHD symptom burden. Axatilimab demonstrated a manageable safety profile in this refractory population, and the most common adverse events reported were consistent with on-target effects of CSF1R inhibition.
These encouraging data that I just described prompted us to initiate the AGAVE-201 trial, the design of which is summarized on slide 11. This is a pivotal dose-ranging trial evaluating axatilimab in patients with chronic cGVHD. Enrollment criteria for AGAVE-201 was similar to the phase I, II trial reported on the prior slide.
The trial enrolled 240 patients whose disease had progressed after two prior therapies, were at least two years of age, and met all other eligibility criteria. Patients were randomized to one of three treatment groups, each investigating a distinct dose of axatilimab administered either once every two weeks or once every four weeks. The primary endpoint is overall response rate by cycle seven, day one, using the 2014 NIH consensus criteria for chronic GVHD.
Secondary endpoints include duration of response and validated quality-of-life assessments using the modified Lee Symptom Scale. We are looking forward to being able to report top-line data from the AGAVE-201 trial in mid-2023 and anticipate making a regulatory filing in relapsed or refractory chronic GVHD by year-end 2023. Our partner, Incyte, will be leading the regulatory activities as laid out in the terms of our collaboration agreement.
With that, I'll turn the call back to Michael. Michael?
Yeah. Thank you, Neil. Just to round out this section, let me briefly turn to slide 12, which highlights the broad clinical and commercial opportunity for axatilimab. The successful commercial launches of Incyte's Jakafi and Sanofi's Rezurock speak to the unmet medical need in cGVHD that translates to a large commercial opportunity.
We believe axatilimab has the potential to provide meaningful clinical benefit in chronic GVHD patients refractory to multiple prior therapies. Through combinations in earlier settings, as well as the opportunity to expand to the U.S. markets, we envision that axatilimab could create significant additional value in cGVHD. We are looking forward to expanding the axatilimab program to include a phase I, II combination trial with Jakafi in cGVHD. The trial will be led by Incyte and is expected to begin in second half of 2023.
Beyond cGVHD, we are also excited about the opportunity to expand axatilimab into fibrotic diseases such as IPF, where the monocyte macrophage lineage plays a key role. To this point, I wanna highlight that axatilimab's benefit in lung manifestations of cGVHD will be the focus of an oral session at the American Thoracic Society Conference on May 24th.
The presentation details the 15 patients in the phase I, II trial that had cGVHD-related bronchiolitis obliterans syndrome or BOS per the 2014 NIH cGVHD consensus criteria. Eight of these patients demonstrated a partial response, and no patients experienced BOS progression as might be expected in the absence of an active therapy. We believe these data support axatilimab's therapeutic potential in interstitial lung diseases such as IPF, where we intend to initiate a phase II trial in the second half of 2023.
I'll now turn the call over to Keith to review our financial results. Keith?
Thank you, Michael. I'm gonna take a few minutes to discuss our financial results for the quarter ended March 31st, 2023. Turning to slide 13, the results of our operations for the first quarter of 2023 with the comparison to 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 first quarter 2023 report, which was filed earlier today on Form 10-Q. I'd like to point out that our net loss for the first quarter was $41.1 million, or $0.59 per share, compared to a net loss of $37.2 million or $0.63 per share for the comparable period last year. This difference in our net loss was driven largely by an increase in employee-related expenses as well as professional fees within both SG&A and R&D.
We ended the first quarter with $449 million in cash equivalents and marketable securities and 69.6 million shares and pre-funded warrants outstanding. Our current cash is expected to provide runway into the second half of 2025, which allows us to appropriately invest to maximize the value of our pipeline, prepare for two potential U.S. commercial launches in 2024, and pursue potential business development activities to build our pipeline. Looking ahead, I'd like to provide financial guidance for the second quarter and full year of 2023.
For the second quarter, we expect research and development expenses to be $38 million-$43 million and total operating expenses to be $53 million-$58 million. For the full year of 2023, the company continues to expect R&D expenses to be $160 million-$175 million and total operating expenses to be $225 million-$240 million, including approximately $30 million of non-cash stock compensation expense. With that, let me turn the call back over to Michael.
Thank you, Keith. 2023 is an incredibly significant year for Syndax. I'm 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. In the near term, we are focused on delivering quality data readouts for our pipeline and potential registrational filings in 2023 for our two lead drug candidates, both of which are first and potentially best-in-class treatments. We continue to look for ways to capture the maximum value of our current pipeline by expanding into opportunities beyond the initial registration indication. Our goal is to bring the potentially encouraging clinical benefits of our lead candidates to even more patients.
As always, I want to express our deep 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 execute on 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.
Thank you. At this time, if you would like to ask a question, please press the star and one on your touch-tone phone. You may remove yourself from the queue at any time by pressing star two. Once again, that is star and one to ask a question. We will pause for a moment to allow questions to queue. We'll take our first question from Madhu Kumar with Goldman Sachs.
Hey, everyone. Thanks for taking our questions. I wanna start by thinking about AUGMENT-102, the salvage chemotherapy combo trial. As that moves forward, how do you envision using revumenib as monotherapy in relapsed refractory leukemias versus in combination with chemotherapy?
Madhu, thanks for the question. maybe I'll turn it over to Neil to address that.
Obviously, the first approval of revumenib will be in the relapsed refractory setting as monotherapy. We have a number of different combination studies either ongoing or planned to enable us to execute the strategy of moving of expanding revumenib into other patient populations in combination with chemotherapy. The combinations are really earlier for earlier phase populations or earlier stage populations ahead of what we anticipate will be the approved indication.
Okay. Maybe on that same note, I'm thinking about the BEAT AML frontline trial where you're gonna have initial safety data at year-end. Could you talk a little more about what specific adverse events you might be monitoring when thinking about a combination of revumenib with venetoclax? I guess particularly the question one can imagine is there any reason to expect QT prolongation could be exacerbated in the combination setting relative to the monotherapy setting?
Thanks for the clarification, Madhu. Yeah, we're anticipating data from the BEAT AML with the combination of, as you point out, venetoclax, emerging, you know, during the course of this year. There's no reason to anticipate that that combination would not be feasible. It's just a matter of doing the normal dose ranging that we need to do. There's no technical reason to assume that we wouldn't be able to proceed into a larger phase, you know, a bigger study, a phase III study in combination with venetoclax versus venetoclax.
Closing on that point, do you expect, like, how much dose reduction for both venetoclax and revumenib might one expect from the combination, kind of given any preclinical work y'all have done with the combination?
Well, no. Thanks again. I mean, preclinically, you can't predict. I mean, we're doing the experiment to do the dose ranging, and it would be, You know, it'd just be remiss of me to speculate on where we'll end up with that. When we have the data, I mean, of course, we'll report them. They'll be reported publicly, we'll discuss it then.
Okay. Thanks very much, everybody.
Thank you.
We'll take our next question from Eva Privitera with TD Cowen.
Hi. Good afternoon. Thanks for taking our questions. We've been getting some questions about the recent paper on resistance mechanisms that arise in around 40% of patients treated with MEK inhibitors after a few cycles. How should we think about this phenomenon in the context of, you know, the high efficacy and the high MRD negativity rates that we've seen in the actual clinical trial?
Yeah. May I start, and then I'll pass it over to Neil. Look, I think, the data that we've generated. Eva, thanks for the question. I think, the data that's been generated, obviously published in Nature, really shows the efficacy of the, of the molecule and the ability to generate, you know, remissions, deep remissions, MRD negative remissions, in a, in a large subset of patients, 30%. I think the idea being overall response rate of over 50%, we are seeing some mutations, and I think they are. It's, it's across all the MEK inhibitor class, we believe, will be affected by this. I think, you know, you had quoted a 40%, up to 40%. I think it was a subset of our patient data.
Important to note that, you know, the great efficacy that we're seeing in the population is really in the presence of some resistance. Of course, some patients will have some resistance over time to all targeted therapies. This is not uncommon. It's been shown with all therapies, even outside of MEK inhibitors. The idea here is that we have, you know, a highly effective treatment. The ability to combine our agent and move it earlier in treatment is a step in the direction of treating patients as early as possible to potentially deal with mutations that arise. It is a small part of the population.
I think importantly, we feel that it's likely our baseline that these mutations were likely in, they were present and probably below the level of detection, and they are probably there. You know, these are fifth line patients, so heavily pretreated and had, you know, received a lot of prior treatment. I think, you know, overall, I think we're feeling that our data is quite strong. We'll obviously be first to market and we'll have a great profile.
I think mutations arise with all these therapies and the ability to combine it, move it earlier in treatment will, you know, over time help us, you know, treat even more patients. We're quite encouraged by the data, and it's always good to be on the front end of the science, knowing that we have, you know, we have a molecule, and we have the ability to understand kind of why some patients actually don't respond.
Thank you for that.
Yeah.
Yeah. You mentioned moving to the earlier lines. How do you expect these resistance mechanisms to impact the use in the frontline setting in combo with other agents and also perhaps in the maintenance setting?
Eva, let me ask Neil to respond to that.
Yeah. Thanks, Michael, and thanks, Eva, for the question. You know, as Michael touched on, it's. Our working hypothesis is that a lot of these mutations are actually present at baseline, but remain below the limit of detection. Just to reiterate a little bit, you know, we don't anticipate any change from what we've already reported out.
The mutation data were derived from the same study that we reported clinical data on, with the median duration of response of nine months. Importantly, also remember that, you know, 80% of patients who had a CR/CRh were MRD negative. This is incredibly important from a therapeutic perspective and very heavily pretreated patient population. As Michael also alluded to, you know, obviously, we're at the forefront of the science here. We understand it.
We're learning more about it, but we understand it to a large extent. We absolutely believe that moving to earlier lines of therapy quickly, which is what we're planning to do during the course of 2024, and actually are laying down the plans for doing that with the combination studies that we just described a little bit earlier, that moving to earlier lines of therapy is important. Because we also believe that combining radiomimetic with standards of care in earlier lines of therapy is more likely to eradicate any clones that exist already and also to preclude the emergence of resistant clones on therapy.
Thank you.
You're welcome.
Thank you, Eva.
We'll take our next question from Anupam Rama with JPMorgan.
Hey, guys. Much for taking the question. I'm just thinking about both the KMT2A data coming from AUGMENT-101 in the third quarter and the future readout for NPM1. How do we think about how much sort of post-maintenance, post-transplant maintenance data we might get from both sort of near term and long term from these cohorts? Thanks so much.
Yeah. Anupam, thanks for the question. Look, I think the data suggests, or at least the data from phase I suggests a lot of patients are going to transplant, and certainly the ones that had reached an MRD negative response, you know, up to 40% or so had moved on to transplant. I think that's a number that's rarely seen in targeted therapy.
I would expect and based on the change in the protocols, you know, in the phase I, we weren't permitted to put patients back on therapy, or they weren't permitted to go back on therapy. That's a, you know, significant change from between the phase I and the phase II, where we have the ability to put patients back on after engraftment. They have the ability to go back on therapy.
That goes for KMT2A as well as NPM1 patients. If you take that forward and relieve the, you know, the tension point of not being able to go back on therapy, you should be seeing a high, you know, I would say a significant portion of patients who go on to get successful transplant to be eligible and go back on. You know, I can't give you specific numbers, but I would say that this is an emerging paradigm in this, in this field of relapsed refractory disease. We're excited to see, you know, what portion of the phase II is in that camp. Yeah, it's... Time will tell.
Thanks so much for taking our question.
Yeah, thank you. Anupam.
We'll take our next question from Yigal Nochomovitz with Citigroup.
Hi, Mike and team. Thanks for taking the questions. I just wanna switch topics to axatilimab and AGAVE-201. Could you just spend a little of time talking about any differences in the patient populations between the phase I, II and the AGAVE-201 trial? Are the 201 patients more heavily pretreated given the uptake of ruxolitinib and Rezurock? Secondly, can you comment at all on what physicians and maybe even the regulators have said with respect to a study that's randomized but does not have a control arm? Thank you.
Yigal, thanks for the question. So let me first start off with the differences in the patient population or to, I should say the lack thereof. I think these are, you know, third-line plus patients. The phase I, II that we enrolled and then read out last year had those patients in it. The patients that we're enrolling in AGAVE-201 have, you know, the same patients. We did see patients who had prior ruxolitinib and also sorry, the Rezurock drug. We are seeing patients in both trials that had prior you know, significant prior therapies, including the newly approved ones. And so we expect the patient population to be, you know, quite similar.
Then on your second question relates to.
Sorry.
Yeah.
Randomization.
As you point out in your implicit in your question is the fact that the trial's randomized three doses, AGAVE-201 we're talking about, but it is, you know, call it single arm. It's not, it's randomized between the doses but doesn't have a placebo arm. That is, in fact, true. I think, you know, this is the design, very similar design to, you know, Rezurock's, the trial that Kadmon ran to get their drug approved, very similar. And obviously, we've had significant agency feedback, and they've reviewed everything that we've done, and we had, you know, alignment on that design. We, we expect that this will lead to a full approval. It's not, it's, not an accelerated approval, but it's a full approval.
Of course, it's all dependent upon us having positive data and submitting a package. I think that's the easiest way to think about it. The design is, sort of tried and true based on what others have done, and we're, you know, we're following what the agency has guided us to.
Okay. Got it. Another important question which I'm sure you've thought about a lot is your IV Q2 week. Obviously, some of the other market participants are oral. Just talk a little bit about how you see that in terms of achieving strong uptake for axatilimab, assuming you make it to market. Do you think that this could be a therapy that would be extended into the community practice as well as to the academic centers? Thanks.
Yeah. Thanks for the question, Yigal. I'm gonna turn it over to Anjali, and she's going to respond.
Hi, Yigal. Thanks for the question. We've gotten very strong feedback from physicians about the overall profile for axicabtagene. It is an IV in a world of approved therapies that are oral, but many of the prior treatments that physicians had been using to control the disease included IV therapies as well as other difficult to use treatments. I think what really drives these physicians is, can I get this disease under control for my patients? You know, the infusion for axicabtagene is pretty straightforward, a 30-minute push infusion. In the trial that we're running, physicians are able to change patients to a once monthly frequency after 6 months. That may be an option for patients in the real world as well.
We're also thinking about subcutaneous formulation that could alleviate some of these differences also.
Okay, thanks. Just one quick clarifying one, Mike, I don't know if you've mentioned. I think you mentioned the 276 milligram, you have that data. Just to confirm, you don't need to do any more clinical work with that dose to obtain that label claim for that dose. Is that right?
Thanks, Yigal. I look, we've said several months ago that we were undertaking a pretty extensive clin pharm program, which is necessary for filing. This was part of that set of work, the clin pharm work. We've enrolled a sufficient number of patients to generate the data that derives the dose that we talked about, the 276. We expect to enroll patients in the, you know, phase II trial, sorry, the approval trial, AUGMENT-101, that, you know, has additional patients not on a strong CYP3A4 inhibitor. That'll be included ultimately in the registration filing.
In terms of actually having data to support what we need at 276 and have that in the label, we believe we have sufficient data.
Great. Okay. Thank you.
Thanks, Yigal.
We'll take our next question from Peter Lawson with Barclays.
Hey, thanks. Thanks for taking my questions. Just a follow-up around the number of patients that you would need to file without that strong CYP3A4 inhibitor.
Yeah. Hi, Peter. Thanks for the question. Yeah, we haven't disclosed how many patients that is. I think we've said, you know, in the past, we'll enroll a sufficient number, of which to justify the dose, and we've done so, and we've talked to the agency, and they've aligned with that. You know, we feel very confident that we have... now we'll have a label. Of course, the drug has to be approved, but the label will show that, any patient, will have, the right dose at the right time.
Got you. Thank you. Then I don't know if you've ever mentioned this, but have you seen responses in AML patients that have already failed, another menin inhibitor?
Thanks for the follow-up. I don't think we've actually called that out in our dataset. I don't know, I don't know the actual answer to that, but we haven't specifically called that out in our dataset. It's a little hard for me to give you a specific answer, Peter.
Got you. Thank you. Just final question around axicabtagene. On the bar for success for the Rux plus axicabtagene for that first line or phase I GVHD combination trial, what do you think that is?
I'm sorry, Peter. Can you repeat the last part again? What do I think what is, exactly?
The bar for success, what do you wanna see?
Oh, the bar.
Yeah.
Right. It is a fair question. Maybe I'll turn it over to Neil to respond to that. I think we're talking about the phase II trial, not the phase I, but the phase II trial. Yes.
Thanks, Michael. I mean, this is being executed by the partner and so, you know, I would address the question to them. Ultimately, the strategy longer term, is gonna be executed by Incyte, actually. I think it would be probably better if you asked Incyte.
Perfect. Thank you.
Thank you, Peter.
We'll take our next question from Kalpit Patel with B. Riley Securities.
Yeah. Hey, good afternoon. Thanks for taking the questions. Maybe a couple on axicabtagene. In the top line readout, do you, do you expect to show any... I know it's top line readout, but do you expect to show any data on the durability for the six months or so follow-up results that you may have?
Yeah, Kalpit, thanks for the question. Look, I think we haven't disclosed what our actual data, the breadth of the data, I should say, that we'll be disclosing on the top line. I think suffice to say we'll endeavor to put enough data out that really speaks to the profile and allows people to have an accurate view on not only how the drug did in the trial, but also what the long-term potential is relative to market opportunity. It's a little bit early for us to speculate on exactly what that, what we're gonna have in the top line disclosure. We do need to spend some time with our partner and, you know, align there.
It'd be a little bit early for me to start, you know, to kinda give you some too much detail there. I think suffice to say, we're gonna put out enough data that allows, you know, investors to understand the profile of the drug and what the long-term potential looks like, at least preliminarily, and allows us also to follow up with a presentation at a medical meeting that we'll be, you know, circling around.
Got it. Do you intend to apply for the Real-Time Oncology Review Program, the RTOR, program for this drug?
Yeah, thanks for the follow-up. I think that's an open question and something we'll have to also align with our partner on. As you may know, I believe Kadmon had applied for that and was granted RTOR with their review of Rezurock. It's something that, you know, we generally don't comment on our regulatory strategy so much as to, you know, what we may or may not be able to accomplish. Certainly it's on the table, and we're, you know, we'll have some discussions about it relative to with our partner.
Okay. Got it. One on the combination trial. Have you or Incyte decided if you'll have a control arm with steroids in that trial?
Thanks for the question. I think it's still under consideration as to the exact design of the trial, and we'll be saying more soon. A little early for us to disclose what the exact design of that trial is gonna look like.
Okay. Thank you.
Thanks so much.
Once again, if you would like to ask a question, please press star and one on your touchtone phone. We'll take our next question from Joel Beatty with Baird.
Hey. Hi. Thanks for taking the question. The first one is on revumenib. Could you discuss the size of the market opportunity for the two separate registrational cohorts and how they compare with each other for both the initial, you know, expected near-term label as well as a longer-term potential?
Yeah. Thanks, Joel. Thanks for the question. I'm gonna turn it over to Anjali. She's gonna describe.
Hi, Joel. Thinking about the relapsed refractory setting, I think we feel that the KMT2A population and the NPM1 population may be closer than expected, given that more of the KMT2A population is likely to relapse and need additional therapy to address their disease. The current assumption is it's closer than what you would expect given the initial diagnosis of NPM1 and KMT2A. Moving to frontline, I think we've given the guidance and a lot of publications suggest about 30% of AML is NPM1, while closer to 10% is KMT2A.
Got it. Thanks. Appreciate that. A question on potential in-licensing of new earlier stage agents. We've heard about that for a number of quarters on conference calls and, you know, and in fact, the two agents that you currently have, you know, are great successes that have come out of that. As those two programs move towards a late stage with pivotal data coming in the next few months, does that affect your company's appetite for going back and in-licensing earlier stage agents at this point?
Yeah. Joel, thank you for that. Look, I think business development continues to be a really important component of our strategy long term. We, as you pointed out, we were successful in licensing the two agents that we're working on. We are moving them through registration trials. We do expect to do a fair amount of life cycle.
We mentioned earlier line trials for both agents, adjacencies other indications, you know, such as IPF for axatilimab, some solid tumors, for revumenib. I think the idea to bring in additional early-stage targeted oncology assets, we've been fairly descriptive about what that means. We're talking about sort of preclinical stage, lead stage, preclinical through phase I.
These are the types of assets that, one, we feel it lends to our expertise, and we can develop them efficiently, to, you know, kinda grow them into assets that have meaningful value in a reasonable period of time and also fit in with the overall kinda dynamic of our company, which is growing to accommodate additional work, but certainly don't want to overwhelm the important work that's going on in the late-stage setting.
Our priority does remain our two key assets, but bringing on additional one or more additional assets of the early-stage variety could add a tremendous amount of value in a reasonably short period of time. Again, it remains the future of Syndax to be able to do that, we are keen to evaluate it.
I will say that the bar remains extremely high for us to trade off and even spend one marginal dollar on additional assets while you have two approved or approvable agents in our midst. We do remain, you know, quite interested but also keep the bar very high to make sure that we bring only the best assets into the pipeline. Lastly, I'll say, the team is quite focused on it here. Of course, the addition of Neil to our team really will, we think, add in that variety. We're, you know, again, excited about business development and realize the scope of work is significant for our current pipeline, look to add over time.
Thank you.
Thanks, Joel.
We'll take our next question from Brad Canino with Stifel.
Hi, everyone. This is Dara Azar on for Brad Canino. Questions from us. On revumenib, are you collecting samples pre and post-treatment for analysis of MEN1 resistance mutation? When should we expect a formal analysis and public data? On axatilimab, what might be available in the top line that can help us confirm differential activity versus Rezurock? Thank you.
Thanks, Dara. I think the answer to your first question is no, we're not tracking that data. We're not, you know... Yeah, I think the idea is that we published the data that we had and, you know, I think we shouldn't expect to see additional data coming out on resistance anytime soon from the current data set. I'm sorry, the second question?
Yeah. What might be available in top line, for thinking about potential differential activity versus Rezurock, for example, anti-fibrotic benefit, anything like that?
Yeah. Maybe I'll turn it over to Neil to take that.
With all the caveats of, you know, the dangers of cross-study comparison, well, what I think your main question is how much data are we gonna top line, so you guys can actually, you know, get an idea about what you're gonna, what you're gonna see. Our anticipation, and of course, this has to be aligned with our partner.
Our anticipation is to top line as much data as we think we need for, you know, to be useful to the investment community and others. But, you know, one caveat is that we also wanna preserve the ability to present the full data set at a forthcoming medical meeting, so we don't wanna compromise that either.
In fact, we're actively in discussions with Incyte, our counterparts at Incyte about what that might look like. We're not gonna be, you know, it's not gonna be minimalist. We will include as much data there as we can, given the caveat that I mentioned about presenting at a medical meeting in the future as well.
Yeah, very helpful. Thank you.
Thank you so much.
We'll take our next question from Justin Zelin with BTIG.
Hi, guys. Thanks for taking the question, and congrats on the progress here. Just a quick question on revumenib. Is there any demand or any interest in either AML or other indications or other combinations that we should be expecting in the future? Thanks.
Hey, Justin. First of all, welcome to Syndax. Thanks for covering us, and looking forward to working with you. look, I think we actually have a lot of interest in ISTs, and there's a whole assortment of work that has either kicked off or will be kicking off related to AML and some of the other disease states that we're looking at. we haven't really disclosed that in any natural form yet.
So I think you'll see some data emerging over the coming months from some of these trials that some of the investigators are doing. we haven't been especially prescriptive about how that's gonna roll out or what those are yet. Stay tuned. I think there's, suffice to say, a lot of interest in what we're doing and the investigators around the world who are not only involved in our trials, but also some that are not, that have asked us to do particular trials of interest. Maybe Neil has a comment to make as well.
Yeah. Thanks, Michael. I mean, there's a lot of interest in revumenib in the AML community and acute leukemia community, AML and ALL communities. What I would say is that we are developing our lifecycle management plans for revumenib beyond the initial indication, as we've discussed, you know, a couple of times earlier on the call in terms of the combinations that we're doing at the moment, what the earlier phase studies look like. We're not ready to discuss the exact designs of those studies. There will be studies that we will sponsor, and then there will be studies that will be conducted through ISTs. Our intention is to have an integrated evidence plan, right?
To be generating data across all relevant patient populations, so that we can fully, you know, inform the scientific or, you know, provide broad scientific knowledge about the molecule. You know, as we're ready to reveal not only the details of our own sponsored studies, but also the broader plan, we'll be happy to do that in the future.
Great. Appreciate you taking the question. Thank you.
You're welcome.
Thank you, Justin.
It appears that we have no further questions at this time. I will now turn the program back over to Michael Metzger for any additional or closing remarks.
Thank you all. We look forward to seeing you at several upcoming medical conferences, including the American Thoracic Society Annual Meeting in May and the European Hematology Association Annual Meeting in June. We'll also be attending the Goldman Sachs Healthcare Conference in June, as well as other investor events which we hope you will join us at. Have a great evening.
That concludes today's teleconference. Thank you for your participation. You may now disconnect.