Syndax Pharmaceuticals Inc Q1 FY2023 Earnings Call

Good day, everyone, and 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, and 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; Dr. Anjali Ganguli, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the Investors page of the Company's website. You can now turn to our forward-looking statements on Slide 2. Before we begin, I 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 from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the Company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC. Any forward-looking statements may represent our views as of today, May 8, 2023 only. A replay of this call will be available on the Company's website, www.syndax.com following its completion. And 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 has deep experience across all stages of drug development and a strong track record of successful drug approvals, which 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. Now turning to Slide 3, 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 2 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 our 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, and we expect to have initial data from several of them by year-end. I will provide details on each of these trials later in the call. Moving to axatilimab, our antibody against CSF-1R. We remain on track to report topline data in mid-2023 from the pivotal Phase 2 AGAVE-201 trial evaluating axatilimab in patients with chronic graft versus host disease or cGVHD, and 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 1/2 combination trial of axatilimab and Jakafi in cGVHD led by our partner Incyte, as well as a Phase 2 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 31. 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. But 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 4, and I'll provide further details on the revumenib program. The Phase 2 portion of AUGMENT-101 was designed as three single-arm pivotal trials with distinct patient populations that enroll independently. These populations include KMT2A-rearranged ALL, KMT2A-rearranged AML, and NPM1-mutant AML. The primary endpoint of each is the percentage of patients achieving CR/CRH with secondary endpoints including durability of CR/CRH response, transfusion independence, overall survival, and safety. Patients who undergo transplant also have the opportunity to be retreated with revumenib in the Phase 2 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 topline 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 the recommended Phase 2 dose in any patient eligible for revumenib. We have determined the RP2D in patients who are not on a strong CYP3A4 inhibitor, as 276 milligrams 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're receiving concomitant CYP3A4 inhibitors. We would expect this dose to be incorporated into the revumenib label at the time of approval. Moving to slide 5, we are excited to now have the Phase 1 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 the CR/CRH with an impressive median duration of CR/CRH response of 9.1 months as of the data cutoff 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 6, 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 and 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 represent 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. Because 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 1 BEAT-AML umbrella trial. As part of our collaboration with the Leukemia and Lymphoma Society, revumenib is being combined with venetoclax and azacitidine to treat newly diagnosed AML patients within 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 and 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 2/3 trial, which could serve as the basis for our future regulatory filings. 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 2 dose and report initial data from this trial in 2023. And the INTERCEPT trial continues to enroll patients as part of the Master Clinical Trial led by the Australasian Leukaemia and 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 the 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 plus 3 in the frontline setting in the second half of this year. Turning to Slide 7, 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 signs supporting the role of the menin-MLL1 interaction in beta-catenin driven tumors. Enrollment is going well in our proof of concept signal-seeking Phase 1 trial in metastatic colorectal cancer and we expect to have initial data from this trial by year-end 2023. Now I would like to turn the call over to Neil to briefly talk about chronic graft versus host disease and why we believe axatilimab, a potentially best-in-class monoclonal antibody therapy targeting the CSF-1 receptor, could benefit patients diagnosed with this disease. Neil?

Thank you, Michael. It's a pleasure to be part of the Syndax team and to showcase today why we are so excited about the AGAVE-201 topline data that we expect to be able to share in the middle of the year. Turning to Slide 8, 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 benefits 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 1/2 data which I'll summarize shortly, we believe axatilimab can provide a differentiated, effective and practice-changing intervention for this underserved population. In Slide 9, I would like to give some background on the disease pathology and the essential role that monocytes derived macrophages have been shown to play in chronic GVHD. The activation, proliferation, and survival of these macrophage populations are regulated through the CSF-1 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 CSF-1R receptor signaling using blocking antibodies such as axatilimab is expected to reduce circulating monocytes and derived macrophages, and consequently, reduce disease pathophysiology. The differentiated mechanism of action of axatilimab combines anti-fibrotic and anti-inflammatory activity, holding the promise to provide a new therapeutic option for chronic GVHD patients, distinct from other approved therapies. The mechanism of CSF-1R blockade also offers the potential for improving the outcomes of patients with chronic GVHD when combined with other currently used therapies. Based on encouraging preclinical data, we conducted a Phase 1/2 trial of axatilimab in patients with chronic GVHD. 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 pre-treated with a median of four prior therapies. Among patients treated in the Phase 2 portion of the trial, the overall response rate by cycle 7 day 1 was 82% with a median time to response at 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 GVHD symptom burden. Axatilimab demonstrated a manageable safety profile in this refractory population and the most common adverse events reported were consistent with the on-target effect of CSF-1R 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 GVHD. Enrollment criteria for AGAVE-201 was similar to the Phase 1/2 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 7 day 1 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 topline 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. And with that, I'll turn the call back to Michael.

Yes. 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 1/2 combination trial with Jakafi in cGVHD. The trial will be led by Incyte and is expected to begin in the second half of 2023. Beyond cGVHD, we are also excited about the opportunity to expand axatilimab into fibrotic diseases such as IPF, where the monocytes macrophage lineage plays a key role. At this point, I want to highlight that axatilimab benefit in lung manifestations of cGVHD will be the focus of an oral session at the American Thoracic Society Conference on May 24. The presentation details the 15 patients in the Phase 1/2 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 2 trial in the second half of 2023. I'll now turn the call over to Keith to review our financial results.

Thank you, Michael. Let me take a few minutes to discuss our financial results for the quarter ended March 31, 2023. Turning to Slide 13. The results of our operations for the first quarter of 2023 and the comparison to prior year's quarter are included in our press release, so we 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 prefunded 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 to $43 million and total operating expenses to be $53 million to $58 million. For the full year of 2023, the company continues to expect R&D expenses to be $160 million to $175 million, and total operating expenses to be $225 million to $240 million, including approximately $30 million of noncash 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, and 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. Additionally, we continue to look for ways to capture the maximum value of our current pipeline by expanding into opportunities beyond the initial registration indications. 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. And I'd also like to thank our committed long-term investors who continue to share in our vision and support us in building Syndax. And with that, I'd like to open the call for questions.

We'll take our first question from Madhu Kumar with Goldman Sachs.

Hi, everyone. Thanks for taking our questions. I want to start by thinking about AUGMENT-102, the salvage chemotherapy combo trial. So 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.

Yes. So I think the first approval of revumenib will be in the relapsed/refractory setting in leukemia. We have a number of different combination phase studies either ongoing or planned to enable us to execute this strategy of moving revumenib into other patient populations in combination with chemotherapy. So the combinations are really for earlier-phase populations ahead of what we anticipate will be the approved indication.

Okay. And maybe on that theme though I'm thinking about the BEAT-AML frontline trial where you're going to have initial safety data at year-end. Can you talk a little more about what specific adverse events you might be monitoring when thinking about a combination of revumenib with VEN-AZA? And I guess particularly, the question is for VEN-AZA, is there any reason to expect QT prolongation could be exacerbated in the combination setting relative to the monotherapy?

Thank you for the clarification, Madhu. We are expecting data from the BEAT-AML study involving the combination of VEN-AZA to come out this year. There is no reason to believe that this combination won’t be feasible. It's simply a matter of conducting the normal dose-ranging procedures we need to perform. Therefore, we have no technical concerns that would prevent us from advancing to a larger early phase data study or a Phase 3 study involving revumenib in combination with VEN-AZA.

Do you expect to see a reduction in dosage for both VEN-AZA and revumenib from the combination based on any preclinical work that has been done with it?

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 remiss of me to speculate. When we have the data, I mean, of course, we'll report them. They'll be reported publicly to discuss with them.

Okay. Thanks very much, everybody.

Thank you.

And we'll take our next question from Eva Privitera with TD Cowen.

Hi. Good afternoon, and 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 menin inhibitors after a few cycles. How should we think about this phenomenon in the context of the high efficacy and the high MRD negativity rates that we've seen in the actual clinical trial?

Yes, I'll begin and then pass it over to Neil. The data we've generated, which has been published in Nature, clearly highlights the effectiveness of our molecule in achieving remissions, including deep and MRD negative remissions in around 30% of patients. Overall, we see a response rate exceeding 50%. Some mutations are appearing, and we believe these affect the entire menin inhibitor class. You mentioned about 40% of our patient subset experiencing this issue. It's essential to acknowledge that the significant efficacy we're witnessing occurs even with some level of resistance, which is typical as patients may develop resistance to all targeted therapies over time. This has been observed across various treatments, not just menin inhibitors. Our approach focuses on providing a highly effective treatment and facilitating earlier combinations to manage mutations that may emerge. However, this is a relatively small portion of the patient population. Importantly, we believe that these mutations were likely present at low, undetectable levels in these heavily pretreated fifth-line patients. Overall, we are confident in the strength of our data. We will be the first to market with a favorable profile. Although mutations can occur with all therapies, our strategy to combine and initiate treatment earlier will help us reach more patients in the long run. We're encouraged by the data, and it's reassuring to be at the forefront of the science with a molecule that helps us understand why some patients do not respond.

Thank you for that. Yes. And you mentioned moving to the earlier lines. How do you expect these resistance mechanisms to impact that use in the frontline setting in combination with other agents and also perhaps in the maintenance setting?

Yes, Eva, let me ask Neil to respond to that.

Yes. So thanks, Michael. Thanks, Eva for the question. So as Michael touched on, our working hypothesis is that a lot of these mutations actually present at baseline but remain below the limit of detection. And so just to reiterate a little bit, we don't anticipate any change from what we've already reported that 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 80% of patients who had CR/CRH had MRD negative. This is incredibly important from a therapeutic perspective in a very heavily pretreated patient population. As Michael also alluded to, obviously, we're at the forefront of the science here where we understand it; we are learning more about it, but we understand it to a large extent. And 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 into earlier lines of therapy is important. So because we also believe that combining revumenib 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.

And we'll take our next question from Anupam Rama with JPMorgan.

Hi, guys. Thanks so much for taking the question. 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 or post-transplant maintenance data we might get from both sort of near-term and long-term from these cohorts? Thanks so much.

Yes, Anupam, thank you for your question. The data, particularly from Phase 1, indicates that many patients who proceed to transplant, especially those achieving an MRD negative response up to about 40%, have indeed moved on to transplant. This is a figure that is quite uncommon in targeted therapy. With the protocol modification, as you know, in Phase 1, patients were not allowed to resume therapy after initial treatment. This has changed in Phase 2, where patients can go back on treatment post-engraftment, including therapies for KMT2A and NPM1 patients. By alleviating the restriction on returning to therapy, we should expect a substantial portion of patients who have successful transplants to be eligible for retreatment. While I can't provide specific figures, this represents a new approach in the area of relapsed/refractory diseases. We're eager to see how many in the Phase 2 trial fall into this category. Ultimately, time will tell.

Thanks so much for taking the question.

Thank you, Anupam.

And we'll take our next question from Yigal Nochomovitz with Citigroup.

Hi, Mike and team. Thanks for taking the questions. I just want to switch topics to axatilimab and AGAVE-201. Could you just spend a little bit of time talking about any differences in the patient populations between Phase 1/2 and the AGAVE-201 trial? Are the 201 patients more heavily pretreated given the uptake of Ruxolitinib and Rezurock? And then secondly, can you comment at all on what physicians and maybe even the regulators said with respect to study that's randomized but doesn't now have a control arm? Thank you.

Thanks for the question. First, I want to address the differences in patient populations, or rather the lack of significant differences. The patients in both the Phase 1/2 study and AGAVE-201 are similar as they are both third-line plus patients. We enrolled patients last year who had prior treatments with ruxolitinib and Rezurock, and we are seeing the same patient types in AGAVE-201. Therefore, we anticipate that the patient populations will be quite alike. Regarding your second question about randomization, as you pointed out, the AGAVE-201 trial is randomized across three doses, but it's designed as a single-arm study without a placebo. This design resembles the trial Kadmon conducted for Rezurock's approval. We have received substantial feedback from the regulatory agency, and they have reviewed our approach, aligning with our design. We expect this will result in a full approval, not an accelerated one, but it hinges on us obtaining positive data and submitting the requisite package. Essentially, our design is based on proven approaches others have used, and we are following the guidance provided by the agency.

Okay. Got it. And then another important question which I am sure you've thought about a lot is your IV Q2 week and 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.

Yes. Thanks for the question, Yigal. I'm going to turn it over to Anjali and she is going to respond.

Hi, Yigal. Thanks for the question. We've received very strong feedback from physicians regarding the overall profile of axatilimab. Although it is an intravenous treatment in a market dominated by oral therapies, many physicians have experience with intravenous options as well as other complex treatments to manage the disease. What's most important to these physicians is whether they can effectively control the disease for their patients. The infusion process for axatilimab is quite simple, requiring a 30-minute push infusion. In our trial, physicians can switch patients to a once-monthly dosing schedule after six months, which could also be a viable option in real-world settings. We are also considering a subcutaneous formulation that may help address some of these differences.

Thanks for the clarification, Mike. I believe you mentioned that you have data for the 276 milligram dose. Just to confirm, no additional clinical work is required for that dose to achieve the label claim, correct?

Yes, thank you, Yigal. We mentioned several months ago that we were working on a comprehensive clinical pharmacology program required for our filing. This effort included the clinical pharmacology work. We have enrolled enough patients to collect the data needed to determine the dose we discussed, which is 276. We anticipate enrolling patients in the Phase 2 trial, called AUGMENT-101, which will have additional patients who are not on a strong CYP3A4 inhibitor. These patients will eventually be included in the registration filing. Regarding the data we need to support the 276 being included in the label, we believe we have gathered sufficient data.

Great. Okay. Thank you.

Thanks, Yigal.

And we'll take our next question from Peter Lawson with Barclays.

Hi. Thanks for taking my question. Just a follow-up around the number of patients that you would need to file without that strong CYP3A4 inhibitor?

Yes, hi Peter. Thank you for the question. We haven't shared the exact number of patients involved. However, we previously mentioned that we would enroll enough participants to support the dosage, and we have done that. We have communicated with the agency, and they are in agreement with our approach. Consequently, we are quite confident that we will have a label, assuming the drug receives approval. The label will indicate that every patient will receive the correct dose at the appropriate time.

Thank you for your question. Have you seen responses in AML patients who have previously failed another menin inhibitor?

Thanks for the follow-up. I don't think we've actually called that out in our dataset. And I don't know the actual answer to that. I mean, but we haven't specifically called out over our dataset. So it's a little hard for me to give you a specific answer, Peter.

Got you. Thank you. And then just final question around axatilimab. So on the bar for success for the RUX plus Axatilamab for the first line or Phase 1 cGVHD combination trial. What do you think that is?

Right. Yes, it's a fair question. Maybe I'll turn it over to Neil to respond to that. I think we're talking about this, the Phase 2 trial, not the Phase 1 but the Phase 2 trial.

Thanks, Michael. I mean this is being executed by the partner. And so I would address the question to them. Ultimately, the strategy longer-term, it's going to be executed by Incyte actually. So I think it would be probably better if you ask Incyte.

Perfect. Thank you.

Thank you, Peter.

And we'll take our next question from Kalpit Patel with B. Riley Securities.

Yes, good afternoon. Thank you for the questions. I have a couple regarding Axatilamab. In the topline readout, do you anticipate presenting any data on the durability for the six-month follow-up results that you might have?

Yes, Kalpit, thanks for the question. We haven't disclosed the specifics regarding the data we will share in the topline report. However, we aim to provide sufficient information that accurately reflects the drug's performance in the trial and its long-term market potential. It's still early for us to determine the exact details of what will be included in the topline disclosure, as we need to align with our partner. But I can assure you that we will provide enough data for investors to understand the drug's profile and its preliminary long-term potential, which will also be complemented by a presentation at an upcoming medical meeting.

Got it. And do you intend to apply for the Real-Time Oncology Review program, the RTOR program for this drug?

Thank you for the follow-up. I see that's an open question and something we need to coordinate with our partner. As you might know, Kadmon applied for that, and it received RTOR during the review of Rezurock. Typically, we don't comment extensively on our regulatory strategy regarding what we may be able to achieve. However, it's definitely a consideration, and we will have discussions about it with our partner.

Okay. And then one on the combination trial. Have you or Incyte decided if you'll have a control arm with which 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. But a little early for us to disclose what the exact design of that trial is going to look like.

Okay. Thank you.

Thanks so much.

We'll take our next question from Joel Beatty with Baird.

Hi, thanks for taking the question. So two, 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 expected near-term label as well as a longer-term potential?

Yes. Thanks, Joel. I'm going to turn it over to Anjali. She is going to describe it.

Hi, Joe. 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. So the current assumption is closer than what you would expect given the initial diagnosis of NPM1 and KMT2A. Moving into 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.

Thanks. Appreciate that. Then a question on potential in-licensing of new earlier stage agents. We've heard about that for a number of quarters and on the conference call and in fact the two agents that you currently have in our great successes that have come out of that. But as those two programs move towards 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?

Thank you, Joel. Business development continues to be a crucial part of our long-term strategy. As you noted, we successfully in-licensed the two agents we are currently working on, which are progressing through registration trials. We plan to engage in extensive life cycle management, including trials for both agents and exploring adjacent indications like IPF for axatilimab and solid tumors for revumenib. We are also interested in acquiring additional early-stage targeted oncology assets, specifically those at the preclinical and early Phase 1 stages. These assets align with our expertise, allowing us to develop them efficiently and increase their value in a relatively short time while fitting into our company's overall growth dynamic. While our primary focus remains on our two key assets, adding one or more early-stage assets could significantly enhance our value soon. We are eager to assess such opportunities, but we maintain a high threshold for investing in additional assets while we have two potentially approvable agents. Therefore, we are very interested but ensure we only bring the best assets into our pipeline. Additionally, our team is dedicated to this effort, and the addition of Neil will contribute positively to our variety in business development. We are excited about these opportunities while acknowledging the considerable work required for our current pipeline as we look to expand over time.

Thank you.

Thanks, Joe.

And 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? And when should we expect the formulation analysis and public data? And on Axatilamab, what might be available in the topline that can help us confirm differential activity versus Rezurock? Thank you.

Thank you, Dara. Regarding your first question, we are not tracking that data, and we do not plan to release additional information on resistance from the current dataset anytime soon. Now, I apologize for the interruption, please proceed with your second question.

Yes. What might be available in topline for thinking about potential differential activity versus Rezurock, for example, anti-fibrotic benefit, anything like that?

Yes, maybe I'll turn it over to Neil to take that.

With all the considerations regarding study comparisons, I believe your main question pertains to the amount of data we will provide as topline so you can gain a better understanding of what to expect. Our expectation is to release as much data as necessary to be valuable for the investment community and others, while also coordinating with our partner. However, we want to ensure that we can still present the complete dataset at upcoming medical meetings, which is a priority for us. Currently, we are in discussions with Incyte to determine what the data presentation might look like. We intend to include substantial data, keeping in mind the need to present at future medical meetings.

Yes. Very helpful. Thank you.

Thank you so much.

And 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 additional investigator-sponsored studies in either AML or other indications or other combinations that we should be expecting in the future? Thanks.

Yes, Justin, first of all, welcome to Syndax. Thank you for your coverage, and I look forward to working with you. I believe there is significant interest in ISPs, and there are various projects that have either begun or will commence related to AML and other disease areas we are exploring. We haven't disclosed this in a straightforward manner yet, so you can expect data to emerge in the coming months from some of these trials being conducted by the investigators. However, we haven't set clear expectations for how that will unfold or what specific studies those will be. So stay tuned. There is, to put it simply, a lot of interest in our work, and many investigators worldwide are involved in our trials, as well as some who are not involved but have expressed interest in conducting particular studies. Perhaps Neil has additional comments to share.

Yes, thank you, Michael. There is considerable interest in revumenib within the AML and ALL communities. We are currently developing our lifecycle management strategies for revumenib beyond the initial indication, as we've mentioned previously regarding the combinations being explored and the earlier phase studies. While we are not yet prepared to discuss the specific design of those studies, we will sponsor some and others will be conducted through ISS. Our goal is to create an integrated evidence plan to generate data across all relevant patient populations, allowing us to provide comprehensive scientific knowledge about the molecule. As we prepare to share the details of our sponsored studies, we will also provide updates on the broader findings in the future.

Great. Appreciate you taking the question. Thank you.

You're welcome.

Thank you, Justin.

And 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 there. Have a great evening.

That concludes today's teleconference. Thank you for your participation. You may now disconnect.