Good day, everyone, and welcome to the Syndax Fourth Quarter 2022 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 the review of Syndax's fourth quarter and full year 2022 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. Briggs Morrison, 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; 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. We can now turn to our forward-looking statements on Slide 2. Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in the Company's most recent annual report on Form 10-K as well as other reports filed with the SEC. Any forward-looking statements may represent our views as of today, February 28, 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 the call over to Michael Metzger, Chief Executive Officer, Syndax.

Thank you, Sharon, and thank you to all of you joining on the webcast today. Now turning to Slide 3. 2022 was a year of growth and strong execution for Syndax. We made great progress working towards our long-term goals, all of which put us firmly on the path of becoming a fully integrated commercial stage biopharmaceutical company delivering two best-in-class products to patients in areas of high unmet medical need. On Revumenib, we made significant progress, enrolling patients in the AUGMENT-101 pivotal trials announced breakthrough therapy designation for patients with relapsed/refractory KMT2A rearranged acute leukemia and presented robust updated Phase I data that further supported Revumenib's best-in-class clinical profile in two oral sessions at the 2022 American Society of Hematology Annual Meeting. Further, we initiated additional Phase I trials designed to test Revumenib in a variety of settings, including combinations with standard-of-care regimens. For axatilimab, we completed enrollment in the pivotal AGAVE-201 trial, published the initial Phase I/II chronic graft-versus-host disease data set in the Journal of Clinical Oncology and made progress expanding the axatilimab development program in collaboration with our partner, Incyte. We are fortunate to have Incyte as a strong collaborator to help us successfully advance axatilimab development. Additionally, in December, we bolstered our balance sheet with a $172.5 million follow-on offering, our cash runway is now expected to extend into the second half of 2025, allowing 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 opportunities. Our focus, determination and unending commitment to patients has propelled us forward to this critical year, a year that we expect will be marked by pivotal readouts and registration filings for our 2B drug candidates, both of which are first and potentially best-in-class treatments.…

All right. Thank you so much, Michael. So as many of you know at the ASH Annual Meeting in December of last year, Dr. Ghayas Issa from the MD Anderson Cancer Center presented updated results from the Phase I portion of the AUGMENT-101 trial in two oral presentations. Of the 60 patients evaluable for efficacy in the Phase I portion, 30% attained a CR/CRh. And notably, in patients treated at the recommended Phase II dose, CR/CRh was the same in both KMT2AR and NPM1 subsets at 27%. The median duration of CR/CRh response was impressive in this very advanced patient population at 9.1 months. There was a high MRD negativity rate of 78% among patients achieving CR/CRh, which is very meaningful in this patient population as it enables patients to proceed to potentially curative bone marrow transplant. We also reported compelling data on 12 patients who achieved a response on Revumenib treatment and then went on to receive a stem cell transplant. And additionally, three transplant patients who were treated with Revumenib maintenance therapy in the capacitate use setting following stem cell transplant or non-myeloablative stem cell boost, two of whom remained in remission for over a year as of the data cutoff. As a reminder, in the pivotal trial, patients can be restarted on Revumenib after bone marrow transplant, the design feature that provides data on the potential role of Revumenib in the post-transplant maintenance setting. Revumenib continues to be well tolerated, and there have been no discontinuations due to treatment-related adverse events. As we look across the development landscape, we believe the data continued to support Revumenib's compelling clinical profile and position it as not only first-in-class, but a best-in-class treatment. I'll now turn it back over to Michael.

Great. Thanks, Briggs. Turning to Slide 7. Given the compelling clinical and safety profile we have observed with Revumenib, our clinical development plan seeks to expand its use beyond relapsed/refractory setting into earlier settings and in combination with approved therapies. Here we highlight our ongoing trials of Revumenib across the full treatment landscape. Starting with the Phase Ib AML umbrella trial. As part of our collaboration with the Leukemia and Lymphoma Society, Revumenib is being combined with venetoclax/azacytidine to treat newly diagnosed AML patients with an NPM1 mutation or KMT2A rearrangement who are unfit for induction chemotherapy. Revumenib is the first menin inhibitor to be included in the trial, which will assess safety as well as initial efficacy. Enrollment is ongoing, and we expect initial safety data from this trial to be available in 2023. Longer term, we expect that positive -- the AML trial results could lead to a Phase II/III trial, which could serve as the basis for 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/refractory NPM1 mutant or KMT2A rearranged acute leukemias. We also expect to have initial data available from this trial in 2023. And finally, the INTERCEPT trial. This trial was recently initiated as part of the INTERCEPT Master Clinical Trial led by The Australasian Leukaemia and Lymphoma Group. This 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 pre-emptive therapy in AML. It is designed to explore the activity of Revumenib, the first menin inhibitor to be included as monotherapy in patients with AML who have MRD-positive disease following initial treatment, a group of patients…

Thank you, Michael. Let me take a few minutes to discuss our financial results for the fourth quarter and full year 2022. Turning to Slide 12. The results of our operations for the fourth quarter of 2022 and the comparison to the prior year's quarter are included in our press release. So I will not repeat them in these remarks. Additional financial details are available in our fourth quarter and full year report, which was filed earlier this afternoon on Form 10-K. I'd like to point out that our net loss for the fourth quarter was $39.2 million or $0.62 per share compared to a net gain of $96.2 million or $1.81 per share for the same period last year. This difference is primarily attributed to the recognition of the upfront payment from Incyte related to the axatilimab collaboration, which we entered into in December of 2021. For the full year of 2022, our net loss was $149.3 million or $2.46 per share compared to a net gain of $24.9 million or $0.48 per share for the same period last year. Again, the difference is largely due to the upfront payment in December 2021 from Incyte. We ended the fourth quarter with $481.3 million in cash, equivalents and marketable securities, including the net proceeds of $162 million from our follow-on offering completed in December of 2022 and 69.3 million shares and prefunded warrants outstanding. Our current cash is expected to provide a runway into the second half of 2025 and covers our aggressive development and pre-commercialization plans for both the Revumenib and axatilimab programs as well as provides us flexibility should we decide to selectively engage in early-stage business development. Looking ahead, I'd like to provide financial guidance for the first quarter and full year of 2023. For the first quarter of 2023, we expect research and development expenses to be $30 million to $35 million and total operating expenses to be $40 million to $45 million. For the full year of 2023, the Company expects research and development expenses to be between $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 now turn the call back over to Michael.

Thank you, Keith. And as you've heard during the call, 2022 was an exceptional year of growth and execution, but it represents only the beginning of what Syndax aims to accomplish in the near future. With two pivotal trial readouts and potential registration filings in 2023 for our two lead drug candidates, both of which are first and potentially best-in-class treatments. Syndax is at the beginning of a significant transition into a fully integrated biopharmaceutical company, serving multiple patient populations of high unmet medical need. In addition, both programs offer the potential for broad franchise opportunities beyond their initial registration indications, adding to Syndax's long-term growth potential. We have ambitious goals and milestones that I've set out for 2023, and I'm confident that we have the right plan and team in place to execute on them. Further, we are in a strong financial position with a balance sheet that allows us to deliver on key near-term milestones. 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 a 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'll turn it back over to the operator and open the call for questions.

[Operator Instructions] And we'll take our first question from Madhu Kumar with Goldman Sachs.

This is Omari on for Madhu. So first -- our first question is, does the FDA now consider KMT2A rearranged AML and ALL cohort for filing purposes? And then second, what are you looking to see from the two different combo studies of Revu?

Yes. Omari, thank you for the question. Yes, I think the answer to the first question, which is the FDA, as far as I heard, does the FDA consider the one cohort for the filing purposes for KMT2A? And the answer is yes. We will be combining both AML and ALL cohorts, [indiscernible] the patients and filing them together. That's the plan. And the second question, I'm sorry, you cut out on the second half of it, so I couldn't hear it. Can you repeat that, please?

Sure. So the second question, what are you looking to see from two different combo studies at Revu?

Once again, it cut out -- I think you said what we're looking to see from the two studies. Is that correct?

Right. From the two combination studies for Revu.

Got you. So the combination studies, we have multiple combination studies ongoing. There's AUGMENT-102, which is the chemo combo, which we'll have data on, we expect later in the year. And we have frontline trials going with ven/aza with beta AML, and we'll be designing other trials in addition to that in the frontline setting. I think we haven't necessarily set out guidance on what we're looking to achieve. I think these are early studies, where we're going to be looking at first of course, safety and early efficacy and trying to establish a recommended Phase II dose. And I think that would be the main objective of those trials, which we'll hopefully achieve by the end of this year.

Our next question comes from Phil Nadeau with Cowen and Company.

Congrats on progress. First, a follow-up on the KMT2A population. So for the readout from the 101 trial, well, it sounds like both AML and ALL patients will be commingled in, I guess, now it's a combined cohort. Will the CR/CRh be analyzed regardless of myeloid versus lymphocytic etiology? Or will there be any stratification for the underlying disease?

Yes. Thanks for the question, Phil. And maybe I'll let Briggs answer that question.

Yes. So Phil, there -- the -- you may recall that when we announced the breakthrough therapy designation and back to Omari's first question, the agency did accept that KMT2A rearranged leukemia is one disease, whether it presents as AML or ALL, adults or kids. And part of the support for that was that the data we presented was a combination of AML and ALL adults and beads. So we did break it out, and we will break it out for the agency to further support that designation, but the analysis is -- we'll be looking at that integrated population altogether?

Got it. Okay. And in terms of the patient numbers necessarily, I know you've said that -- you've already recruited them. Is the number of patients equivalent to what we thought you were going to roll in cohort 2A and 2B in the study? Or because they're not being combining -- not being combined, is the required number of patients actually equivalent to just really one cohort worth of patients?

Yes, Phil, thanks for the follow-up. I think we're going to -- well, we haven't really guided, we're not planning to guide on a specific number of patients in the combined cohorts. I think what we've said is that it's a sufficient number based on both [indiscernible] feedback. We feel that we're aligned on a strategy to have a sufficient number of patients that will constitute a filing in the -- by the end of the year. We'll have that data, of course, in the third quarter. But we're -- at this point, we're not guiding specifically to how many patients are in the pooled analysis.

Got it. Okay. And then -- last question on revumenib before one question on Axa. In the NPM1 pivotal same data -- or sorry, enrollment completion in the second half of the year, that seems to suggest data the first half of '24, maybe mid-'24 based on your prior guidance for the KMT2A population. Is that a fair assessment? Or is there some reason why there could be a longer interval between enrollment completion and data in the NPM1 patients?

I think the same rules apply. I think we said we follow patients for six months. We're not being specific as to exactly when in the second half, we'll have the NPM1 enrolled. So I'm going to be a little bit conservative and not project that when we'll have top line data yet in 2024, but I think we -- that's -- it's the same rules that apply to the KMT2A population as the FDA will be following them all for six months.

Great. And then last question for us on axatilimab. Would you be willing to provide any additional details on the IPF Phase II now? Or will we have to wait until the trial is underway?

Yes. Thanks for the question, Phil. We're excited to obviously get that trial started, and we'll probably share more details on the trial and the design once we're underway. I think that's probably old to say.

Our next question comes from Anupam Rama with JPMorgan.

This is Priyanka on for Anupam Rama. Just a quick question from us. Between the two KMT2A cohorts, could you provide any color or clarity on enrollment breakdown?

Yes. Thank you for the question. As I said previously, we're not going to give specific guidance on how many patients were contributed from the -- either of the two cohorts. What we're guiding to is that, we have a sufficient number that we can complete the analysis, and we'll provide that top line data in the third quarter. So I think there's a lot to be satisfied with that for now. I think that's the guidance, specifically.

Our next question comes from Yigal Nochomovitz with Citi.

This is Ashiq Mubarack on Yigal. Just on NPM1. Do you have clarity on the number of NPM1 patients you need to enroll to hit your time line guidance? Have you spoken with the FDA on specifically NPM1?

Yes, thanks for the question. We had previously disclosed 64 patients, NPM1 patients as we had laid out the three cohorts. 64 patients is the number that we'll look to enroll. And we have, of course, spoken with the agency about not only NPM1 and KMT2A, we've had a fair amount of interaction with them over the several months since we started this program. And we've aligned on our -- not only our design, but all the statistics that go into each of the cohorts. So yes, nothing really new there. It's still the same number of patients that we had guided to use.

Okay. Are you able to provide any clarity on where you are in terms of fitting the 64 patient number?

Only that we've -- yes, thanks for the follow-up. Only that we've guided to the second half of the year. Sometime in the second half of the year, we'll be able to announce that we've enrolled to 64 and you'll be able to figure out from there exactly when whereabouts we are with presenting [count like that].

Okay. Got it. And maybe one more on axatilimab. For the frontline combo trial with ruxolitinib, which you're starting later this quarter, how should we be thinking about maybe the combined ability of axatilimab with ruxolitinib, maybe in terms of the potential for overlapping toxicities maybe such as pneumonia or liver enzymes, for example. Is there any color you can share on combinability?

Thanks for the question, Ashiq. Maybe I'll have Briggs address the overlapping toxicities. And just to point out, I think the trial -- this is Incyte's combination trial that they'll be kicking off. And I think the guidance is, later this year, we didn't specify the first quarter in particular, but I think it's a trial we're all looking forward to and maybe breaks, if you could address the overlapping target?

Yes. Look, I think that was part of the keen interest of Incyte and wanting to partner with us on axatilimab because at least if you look at the monotherapy toxicities of each agent, they look like they would combine quite well. But that, of course, is the purpose of the initial phase of the combinations is to characterize that. But going into that trial, we would be quite optimistic that we can get full doses of both agents.

Our next question comes from Brad Canino with Stifel.

This is Brad. It doesn't sound like I can get more out of you on AUGMENT-101. So maybe I'll ask about the status of the Phase I [clinical framework] you're doing around the multiple doses of Revu for the SIP inhibitor strength. Should we expect the data disclosure from that this year?

Brad, thanks for the question. As you, I think, pointed out in your question, these are supportive -- these are supportive trials or this particular trial is a supportive piece of our filing, potential filing for Revumenib and that work is ongoing. I don't think we've guided to when we would necessarily disclose data from that trial. I think we -- related to certain pieces of this, there may be -- there will be data that comes out in the ultimate filing when we disclose data. But I don't think there's any particular time line related to when we might disclose that particular study. But thanks for the question.

Okay. And then maybe one on the safety data for the Beat AML because it's exciting to get some combo data this year. I guess to set expectations for that, can you discuss the Revu dose being used there? Is it all the 163 mg on a strong SIP? Or is there any dose escalation of Revu taking part in that combo? And then for the ven/aza component, what is the schedule for then? Does it require continuous dosing? Or can physicians use the shortened schedule that's often used in clinical practice now?

Yes, Brad, very good question. Maybe I'll let Briggs address both of those.

Yes. So starting is the standard Veneza-labeled regimen. Obviously, there are protocol-specified dose interruptions, if needed, but the request was to start with the labeled regimen. And then there is a dose escalation component to the revimenib. But everybody is on a strong inhibitor.

Next question comes from Peter Lawson with Barclays.

I guess just around NPM1, just any update around how enrollment is proceeding there? And then I've got a question on axatilimab.

Thanks, Peter. Thanks for the question. NPM1 enrollment is going well. It's KMT2A is going well as well. So I think they're both -- there's great enthusiasm certainly since ASH, I would say that investigators have really engaged with us and have it's really related to the data that they saw at the meeting. And so NPM1 enrollment is going well. So there's -- and I think that relates to our ability to complete enrollment in the second half of this year. And then you had a follow-up.

Yes, just around axatilamab, just with Sanofi's Rezurock with that launch. Kind of how do you look at that and gauge your own potential launches? How should we think about peak revenues? And whether you think this is ultimately a single agent or combination agent regimen?

Thanks for the questions, Peter. So, yes, look, I think we -- you heard in my remarks, Rezurock has done well. It's first year sales upwards of $200 million to $250 million in sales, impressive. This is -- our drug has a different mechanism of action, and we think impressive results thus far in its clinical trials. And I think the opportunity here in chronic graft versus host disease is to access patients in the relapsed/refractory setting. I think these patients tend to over there -- course of their treatment journey, they tend to get multiple therapies, they cycle through the different therapies. And so our opportunity, we think, is what Rezurock and/or Jakafi experience in the third line, the ability to pick up meaningful share. Ultimately, this -- and that's as monotherapy -- but ultimately, the opportunity here extends itself well beyond just monotherapy into potential combinations. Rezurock is -- has its own opportunity for combination potentially. But the mechanism of action of our drug is not overlapping with Jakafi. And so that's the -- as Briggs pointed out, that's the reason why I think we're so excited about being able to combine it in the frontline setting and potentially reduce the use of steroids, which could really expand the use of this drug beyond what Rezurock has even shown in relapsed/refractory in the first year. If you think about that a little harder, first year sales to $200 million to $250 million, that's showing to be a potentially very large opportunity. Again, that's just in relapsed/refractory third-line-plus disease. And so the opportunity to go in combination and get the patients earlier in their treatment journey, I think really pretends well for our drug. And I think, was there something else to your question, Peter?

And our next question comes from Kalpit Patel with B. Riley Securities.

Yes. You mentioned that the enrollment for the NPM1 cohort is going well. So I'm just curious about the timing differences versus the KMT2Ar cohort. Is that just a function of when these trials started enrolling? Just trying to understand the gap there.

Yes. Thanks, Kalpit. Good question. Look, as I said, we are pleased with the enrollment for -- and the physician enthusiasm for both NPM1 and KMT2A. I do think that BTD has its sort of advantage to our filing strategy for KMT2A and the ability to combine cohorts, may have something to do with our ability to kind of move more -- slightly more quickly with KMT2A. So I think that's part of it. The other part of it is that KMT2A, there's probably a little less competition for patients with our competitors. And NPM1 may be drawing more patients in various studies. So I do think that there are some competing factors here, some contributing factors here. But ultimately, I think we're doing quite well with NPM1, and we feel that getting to market as quickly as we can with KMT2A will advantage us greatly as we bring data behind for NPM1 and hopefully get that approved as well.

Okay. And then maybe one question on the combo studies. Has the dosing commenced for the Beat AML study. I think you stated that we're just expecting safety this year. So I was just wondering if those things started yet.

Yes. Thank you for the question, Kalpit. So yes, the combination studies have initiated. So there is the -- again, the AUGMENT-102 chemo combination that has been enrolling patients as well as the Beat AML trial that is also enrolling patients, so they both start.

And our next question comes from Bert Hazlett with BTIG.

Just one or two for me. Could you just remind what the consideration Revumenib post-transplant? Is there a regulatory or an indication strategy there? Or -- are you thinking about that as a companion listing or publication strategy? Just could you just frame how you're thinking about that from a regulatory perspective?

Sure. Briggs, do you want to take that question from Bert, please?

Yes. So Bert, in the ongoing pivotal trials, we allow patients to go back on to Revumenib after their -- if they have a response go to transplant, they can go back on Revumenib. That work in the pivotal trial, we don't anticipate a label indication for that. Best-case scenario is, we might be able to describe in the label that how the trial was conducted. So I think that information will be mostly gotten out into the community through publications. It does set us up for potentially a formal maintenance trial down the road, but the way we're handling it in the pivotal trial there won't be a claim regarding maintenance.

Okay. That's helpful. And then just shifting gears from a corporate perspective, back to axatilimab, I believe you have a co-promote option there, and you've hired a Head of Commercial relatively recently. How are you thinking about that decision? And is there a particular timing in which that needs to be executed on your part?

Thanks for the question. Good question. You're correct. Our agreement with Incyte does include a co-promotion option on axatilimab. That election is made in proximity to filing. So it is something that we'll have to kind of let people understand a little bit better in the coming months as we get closer and closer to that time point. Obviously, we'll have a filing, as we said before the end of the year. So we're thinking actively about it. I would just say that we have two programs that, as we described today, as you know, that are really on top of one another in terms of timing, both for filing and then approval. And so the commercial opportunities, while not the same, are -- may have some synergy in terms of the doctors that are being called on and how we promote these products. So the thought potentially that there could be some very nice synergy between what we do with Revumenib and axatilimab, and so that we're thinking actively about whether the co-promotion option makes sense for us.

Okay. And I know maybe early, but any thoughts on sales force sizing, infrastructure, things like that?

Sure. It's a longer conversation. I would say that we -- this is a focused commercial effort, meaning that these are not very large patient populations. More importantly, they are covered by a reasonably focused number of physicians. And so the field force to cover it is somewhere in the order of 40 to 50 physicians -- 40 to 50 reps. We'll refine those estimates and start to give some more color to what the organization looks like that we're building, but we are actively engaged in bringing in leadership to the Company in order to be ready in time for launch for both of these products.

Our next question comes from Joel Beatty with Baird.

First one just on the pool KMT2A cohort. Do you anticipate that the efficacy will be presented just for the pooled cohort on the label? Or could there also be a breakdown of AML and ALL on the label?

Yes, Joel, great question. I think that was sort of alluded to or part of another question that was asked earlier. The strategy for pooling is that the -- we'll be presenting a total number of patients and they'll be analyzed. I think the -- of course, the agency will look at all the subsets, and we'll have a breakdown of that, and I think that will be part of our package. But essentially, the analysis, the primary analysis that will be done is on a pooled patient.

Okay. And then a question on R&D accounts because it looks like we'll ramp up over the course of 2023, any priorities that you anticipate will be a part of that increase selling?

Yes, Joel, this is Keith. I'll take that one. So a lot of the increase in 2023 will go towards the initiatives that Michael laid out in his comments. We have a pretty expansive development program for Revumenib to realize the full potential, the current pivotal programs are focused in relapsed/refractory, obviously. But going forward, you heard Michael expand upon all of the work needed to, again, recognize the full potential, looking front line combos, maintenance therapy, et cetera. Additionally, in anticipation of a filing by year-end and to be ready for a launch in 2024, there will be an increase in CMC/tickoff expenses to get our registration batches manufactured. Remember, we do have not only solid tablet formulation that we'll be bringing to market, but also a liquid formulation as well. So that's the majority of the increase.

It appears we have no further questions at this time. I'll turn the program back to Michael Metzger for any additional or closing remarks.

Great. Thank you, operator. Thank you all. We look forward to seeing many of you at the Cowen and Barclays Healthcare Conferences in the next few weeks in March. And with that, I wish you all good night. Thank you.

This does conclude today's program. Thank you for your participation and you may disconnect at any time.