Syndax Pharmaceuticals, Inc. (SNDX) Earnings Call Transcript & Summary

Welcome to Citi's biopharma back-to-school Summit. So sharpen your pencils, take out your notebooks. It's my pleasure to have with me -- well, I should say I'm Yigal Nochomovitz, senior biotech analyst here at Citi, and it's my great pleasure to have with me senior management from Syndax Pharmaceuticals, of course, Michael Metzger, CEO; Nick Botwood CMO and Head of R&D; and Keith Goldan, Chief Financial Officer. So welcome all of you. Thank you so much for doing this.

Michael, obviously, a lot's happening in the space. You have 2 FDA approvals, obviously. One of the questions we're getting recently is just how things are going with revenue for given that you have the expanded label. So maybe we could start there. Talk about NPM1. What are the forces driving your view that you are taking a leading share of that market? And then we'll go from there.

Well, thanks, Yigal. Good to be with you. Good to be back to school. Well, look, I think it is a very exciting time for the company, a lot going on. Really important launches, 2 important launches. I think what we've done, we've really reset the category in AML in terms of what Alan look like, which is really exciting. I think people maybe missed that through the trees a little bit. But we're annualizing at about well north of $200 million for second year in a which is fantastic, and this is -- how we have 2 indications, KMT2A and NPM1, very broad label best-in-class efficacy. And I think the efficacy story is really resonating with physicians using the drug in a [indiscernible] combination and really building the men's story and the leadership that we've exhibited is really coming through. So we're very [ vetted ] about the forward. We're excited about what we're building with that franchise. I think NPM1 has become an increasingly important part of our story. Both new can starts and time on therapy. So duration of therapy is an important driving force behind the whole franchise. Recent data Medicare care data as well as scrip data indicates that we are firmly in the lead in terms of new patient starts for NPM1 as well as KMT2A. So we're really moving well dominating, we're at 85% market share plus in the category. So thinking about relapsed/refractory, I don't think you can get more dominant than that really building the business, and it's growing, right? We've shown 6 quarters quarter-after-quarter growth, substantial double-digit growth, and we expect that to continue. So that's where we are today, and we're certainly going to continue to build as we get to a which is a hopefully right around the corner. I mean we're really moving quickly and rolling tries that we'll talk about how we're doing. And certainly, the data that we have in the upcoming milestones, catalysts will talk about really quite exciting year for us.

Okay. And so just you mentioned some specifics there in terms of some of the share numbers. So the 85% share, that's sort of across both categories.

It is.

Okay. All right. And we're getting a lot of questions about the competitive positioning with regard to NPM1. Anything there you want to share more specifically regarding the confidence you have that you are taking the lead in there.

Well, I think the numbers speak for themselves. We posted $55 million in the last quarter, competitor did about 9%. So you can see that. I do also see are encouraged by what physicians tell us about the profile and how they're using the drug, using in monotherapy, using in combination with standard of care being supported by the real world data that we're putting out as well as what we're producing in trials and so forth. So there's a lot of support. And when we speak to the physicians, they tell us we're the go-to menin inhibitor. And we expect that to continue to build as we produce the data that we have set out to bring it forward. And that's really the set of it is quite positive.

One of the other drivers, obviously, of the revenue picture is the post-transplant restarting and the maintenance there. So can you talk about that aspect of it in terms of getting to a goal. I think you've referenced something in the 70% to 80% range in terms of getting people restarted on revenue Forge?

Right? So it's a very important dynamic. As you all know, if you've been following our story, Revuforj is a opportunity to bring people to transplant in numbers that we've never seen before in AML with patients who have KMT2A and NPM1. So we're seeing transplants across both indications, more transplants, of course, on the KMT2A population. And right now, we're at about 50% as of last quarter, 50% of the patients going to transplant, which is remarkable. It's remarkable because it drives the ability to get into -- you see -- you get into a response first and then you get the transplant and then you have the opportunity to go back on maintenance and maintenance can extend the life of patients and keep them in remission. And so that's what we're setting out to do. The target is we tend to call it the target for menin, it's really what do we think we can achieve, how many patients will go back on maintenance after transplant. We expect the transplant numbers to move up, probably not meaningfully beyond 50% of the patients but could be higher than 50%. But really, the opportunity to bring patients back 70% to 80% is roughly the target, and we say that because, unfortunately, some patients don't make it through transplant, having nothing to do with the revenue for it, but just the transplant perceived themselves. And then you have patients who have a choice in the matter. And obviously, there are some things that intervene and so forth. But a high, high percentage of patients going to maintenance will continue to drive that franchise in terms of TRx, and we see that steadily increasing each quarter, and that's a very positive forward indicator for the growth.

And with that dynamic, where do you see the sort of steady-state duration shaking out long-term -- we've this for the models.

Yes, it's great for the models. Look, I think we've spoken broadly about 6 to 12 months of duration of therapy in the relapsed/refractory setting, and I think we'll be going to be there this year, sure. But it's also very encouraged. If you look at the data from the last quarter, we were seeing patients who had come back from transplant beyond -- they were on an average of 9-plus months. So again, taking very, very well to even exceed our expectations, which we were very encouraged by last quarter. We would hope that would continue to move up, no reason to say that it wouldn't. So this is, again, it's an ongoing and unfolding story, but it's a very positive cater of what could come in long-term duration.

And of course, there's a ton of interest in the earlier line, you mentioned already the frontline opportunities. And would love to get Nick's thoughts on the structure and strategy there. But you've referenced revenue forge potentially being a $2 billion product. So I gather that includes contributions from the earlier settings. So maybe we could just kind of walk through what the thinking is there in terms of getting into those earlier lines and then the strategy with the several -- the 2 important frontline studies you're running.

Certainly, the data that we have in combination with REV and thrombin standard of care for newly diagnosed patients is [indiscernible]. So we have data sets you're familiar with, save Beat AML or 7+3 trials those Phase I/II trials have grown in size and really shown us fantastic category-leading data to date. We'll have updates important data at the end of this year that will further elucidate that profile. But we think we've really derisked the frontline opportunity quite a bit with these data. And so with category, a category-leading agent like Revenue Forge and the ability to move quickly to frontline and be there first, with a best-in-class profile with a lot of supporting data. It helps to just drive the story in the intermediate time between now and we get to front line. But as you mentioned, we believe it's a $2 billion-plus peak revenue opportunity in the U.S. for Revenue Forge, driven by a first mover advantage and best profile. Again, that's across both fit and unfit, and of course, assume some participation again in relapsed/refractory, leading category and relapsed refractory, but the market will probably change as we get to frontline, and we think we'll have a dominant share as well. So it's a long-term view, which we feel is very well supported by data today. But maybe Nick can take us through that.

That would be great because I get the question around the reason you're doing 2 frontline studies, that would be great to into the details there.

Well, firstly, thank you, Yigal, and a pleasure to be here. Thank you for the invitation. A very exciting time at Syndax and happy to talk about the progress we're making in newly diagnosed AML. We really feel this is the next step in terms of the life cycle of Revenue Forge. And it's an exciting time to be on the program because we're gaining great momentum with both of those 2 pivotal registrational first-line studies, very satisfying now to see sites being set up worldwide, activated, patients being enrolled, great momentum behind the study, a series of large, extensive investigating around the world supporting those studies and we're making good progress, and it's exciting to see that, and we're just looking forward to those studies completing and reading out. Now let me just break them down a little bit. I think most people are familiar, but just to remind everybody how we're approaching this, we have 2 pivotal studies, and then there are some additional steers that support innovation and clinical practice, which we think are important as well and could be quite differentiating. But let me start with the 2 pivotal Phase IIIs. We have the EVOLVE-2 study. This is done in collaboration with the HOVON group. So an internationally renowned well-recognized leadership group in the space of hematology, you have been working closely with now for 2 years. This was the first pivotal Phase III registration study to get started enrolling for a menin inhibitor, and we started in May 2025. So this has been set up for quite a long time and is enrolling very well, and we're happy with the progress. We also are working in collaboration with the Beat AML consortium in the U.S. And so we have great support, and it's a catalyst enrollment having that group now enrolling in the U.S. working in collaboration with HOVON. Just as a reminder, this study has dual primary endpoints, so they're independently powered statistically, either 1 of them could lead to a positive study. One of the dual perm endpoint is complete response, and the other is overall survival. So these are very clean endpoints. Overall survival is obviously the gold standard in HemOnc studies, and we hope to be able to demonstrate a survival benefit and complete response rate is a surrogate endpoint that we believe could support accelerated approval and indeed has been used before for accelerated approvals in this setting. So that's the patients who are unfit for intensive chemotherapy. And then we have a separate international Phase III study called REVEAL. This is done under Syndax sponsorship. We're working with a leading CRO, PAREXEL to execute that study internationally. It's a true international study sites across the United States throughout Europe and also important Asia. So we have China, Japan, Korea, all enrolling in that study. So great momentum behind it. We're going to be a several hundred sites worldwide, and we're doing very well. This is in combination with 7+3 intensive chemotherapy. It again has dual primary endpoints. We're looking at CR, but in this instance because the CR rate is quite high for patients with the get intensive chemotherapy, it's MRD-negative CR. Now that endpoint has not been used for accelerated approvals in the past. But we feel we have time and sufficient data to support it as a potential for accelerated approval and could really -- that could be quite groundbreaking and innovative and we're working closely with health authorities to support that endpoint. And then the other dual-endpoint is event-free survival. Both of those studies are going well. We haven't guided on the time lines. This is a very competitive space. We want speed. We want quality, but we also want a good result. So we haven't guided specifically, but you can probably estimate roughly where we are given the start rates and roughly the size of the studies. I would note that these studies are somewhat smaller than the competitors in the menin space, and there are specific reasons for that. Michael alluded to the strength of the data, and we can maybe talk a little bit about that. We have generated really compelling data for both a ven/aza combination, working with Beat AML and MD Anderson, the so-called save, but also with 7+3 therapy. Those are very supportive. That's allowed us to power the studies appropriately. And also our FIT newly dose study is only 2 arms, whereas the competitor studies include 3. And we made a very deliberate and conscious decision to do that. And we could maybe explain why in due course. But that was a decision. So we're feeling very confident about those. Now I would just mention 1 last thing, Yigal, which is in addition to those 2 pivotal registration studies, we want to be differentiated and also to innovate as the leaders in the menin class. And there are a couple of things that we're doing separate to that. One is called the [indiscernible] study. This is a study we're doing in collaboration with University of North Carolina, [ dossier ]. And this is for patients who are -- who have KMT2A disease, where we have consistently demonstrated the best data, and this is for patients that would otherwise be fit to receive intensive chemotherapy. They're actually going to get ven/aza plus [indiscernible] with the idea of getting them to stem cell transplant without all of the comorbidities usually associated with intensive chemotherapy. So that's differentiating, and we think could are a viable alternative for those patients. That's number one. And then number 2 is another study. I'm very excited about the MAINTAIN study. This is a study we're doing with caricature go to the Dana Farber Cancer Institute. This is the first prospectively randomized study, specifically addressing the question of maintenance. Michael talked about the importance of maintenance. And to be clear, we don't promote maintenance. We still have to establish the burden of proof. We know physicians want to treat their patients in a maintenance after transplant because they know that they have a high likelihood of progression. This will actually attempt to address who should get maintenance and what the benefits and maintenance are and how you optimally manage patients. So that's a kind of overview of our newly diagnosed program. And I know I was a little long, but hopefully, that was helpful.

That's excellent. And I'm gathering that the fact that you've split, as you pointed out, the fit and unfit into 2 separate studies. Does that increased efficiency? Does that increase speed? Is there a specific reason for that?

Yes, very briefly, that was a conscious decision, and I'm very happy with that design. It allows us flexibility, ones under our sponsorship when we leverage the benefit of what oven, which is great, and it allows us to be flexible should we need to change or amend either of those studies. So I'm very happy with the model in which we're executing those.

And I know you're not ready to provide time lines yet, but I guess next year would we get a sense as to when we may see the top line? Or is it still a bit too early to know that?

Well, we may guide in due course for now, we're just focused on execution and we'll see, but we're feeling good about the momentum behind those studies.

Okay. There's another mutation which is less common, this 98. Can you just comment briefly on how you're going to get that 1 into the regimen.

Yes. Let me try and be brief because I get excited about all of this science and the opportunity, and I want to go off too long. So I could like talk a lot about 9, but this is a very important subtype of AML. And the reason it's exciting is because these patients are highly chemo-refractory and previously didn't have really a treatment options available to them. And we always like focusing on these areas of high unmet need. And because of the breadth and the profile of revumenib across NPM1, KMT2A new 98 hours, a little like KMT2A, it's a relatively small subsidiary, although I think actually more prevalent than we think because physicians are now increasingly looking for it. So it could be as high as 3% to 5% of AML. And we presented some data at EHA in a series of about 28 patients, which is quite a lot, showing just over 1/4 of those patients actually showing some sort of response, which is really encouraging for a subset of patients who are refractory to chemo who really don't have a treatment option available to them. So that -- those data, working with MD Anderson being prepared for manuscript, and we think that, that could be very important data for the NCCN guidelines committee to consider at least as to whether they meet the criteria for guidelines. But given the paucity of options for those patients, that's something we would be keen to submit to them in due course when we have the manuscript.

Right. We look forward to that. Let's move on to [indiscernible] for a bit. There's obviously a lot of excitement there as well, not just because of the strong launch with your partner insight. But you have a very important readout coming up, which is highly anticipated in a lung disease called IPF. So we'd love to understand that study a little bit. There's a lot of interest in what you need to show there to be -- have a good target profile to take it forward. So can you introduce that to us and sort of explain how you're thinking about what you want to achieve there.