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

Here on this our third day of Bank of America's 2025 Healthcare Conference in Las Vegas. My name is Jason Zemansky. I'm one of the mid-cap analysts here at the bank. With me on the stage is my associate, Cameron Bozdog. And for this slot, I'm very pleased to have join us, Mike Metzger, CEO of Syndax Pharmaceuticals and the rest of the Syndax team. Mike, thank you so much for joining us.

Yes, Jason, thank you. It's always a pleasure to be here with you, and thanks to Bank of America for inviting us to the conference. I think exciting time for the company, for sure.

Absolutely. Maybe just to start a little broadly for those who may not be as familiar with the story, can you talk about your 2 recently launched commercial agents and why you think they're differentiated?

Sure. So as, Jason, mentioned, we do have 2 really exciting new agents that have entered the market. One is Revuforj, which is indicated for KMT2A acute leukemia for adults and pediatrics. This is a rare form of leukemia, but a very difficult diagnosis or a difficult prognosis for patients. We are the first in the market or as a menin inhibitor. This is first best-in-class profile for KMT2A, and we'll be expanding into another indication we hope pretty soon here with the launch of -- approval and then launch of NPM1, but this is a really exciting agent for patients who have acute leukemia and haven't had anything for their disease up until this point. And the other is Niktimvo, which is a CSF-1R antibody. This is a first of its kind antibody for chronic GVHD, third line -- indicated for third line, also approved last year and launched this year, very exciting in the fact that a new mechanism of action for patients who have inflammatory and fibrotic aspects of the disease, which is particularly difficult to treat. And so this is a new offering for those patients, and we're partnered with Incyte on the promotion of that product and development of that product. And so now we have 2 agents in the market, very differentiated position, both in terms of their profile and what they offer on the efficacy side, but also on the safety side as we learn that patients not only are getting the drug, but staying on drug and doing quite well. So that's early days of launch, but very encouraging first quarter for Revuforj and the first 2 months for Niktimvo, where we're sort of outpacing even what we thought was possible at this stage. We're very excited about the growth.

Well, perfect. There's definitely a lot to talk about. But before we get into this, I'd really like to introduce Nick Botwood, your newly Head of R&D and CMO. Maybe if you could just take a second to kind of explain what really attracted you to the company and kind of as you look for these 2 recently launched products, what are some of the puts and takes as you think about the trajectory of the launch?

No. Thank you, Jason, and I'm thrilled to be here. Thank you for the invitation. And just by way of background, I'm a medical oncologist, and I've been fortunate to develop some important drugs over the last couple of decades, really transforming outcomes with firstly solid tumors, tyrosine kinase inhibitors and then PD-1s. And when I look at Syndax, which is a somewhat unique as a biotech company, it's extremely rare to see a company with 2 successful approvals in a very short space of each other, an NDA and a BLA with 2 therapies that, again, really have an opportunity, I think, to transform outcomes in difficult-to-treat diseases. And as I have been following the progress of Syndax, I was attracted not only to the ability of a company of that size to execute so flawlessly in terms of drug approvals, but also now commercialize in settings where really there's been very little improvement in those standards of care. And throughout my career, that's attracted me. From medical school onwards, leukemia and chronic graft-versus-host disease has seen very little innovation. And I think now we're at the frontier and leading in a space where we have the opportunity to really impact outcomes for these patients who so desperately need new therapies. So my background is both in drug development and also in commercialization. I consider myself a commercial and strategic R&D leader, and it's a great opportunity to join a company where I can both drive development of these very promising assets that are already in the clinic into newer indications, so specifically into combinations of therapy and into frontline, but also to support the commercialization of these assets and helping patients now because it's in the clinic. And I'm excited about the growth trajectory of that. So it's a fabulous time for me to join the company. The last thing I would add is that my early exposure to the teams in Syndax and my team, the research and development team that includes medical and all of the other functions that are supporting our research and development engine are incredibly strong. And that's always an important factor for me when I consider coming into a company. This is an incredibly talented and driven group of individuals. And I think they're really poised to do some very, very exciting things for patients.

Got it. Makes sense. And then this is going to be top of mind, I think, for most investors. But yesterday morning, the abstract titles for EHA were announced. Maybe Mike and Nick, you can sort of talk about what to expect as the conference unfolds in a couple of weeks.

Yes. I'll just say a couple of words and then I'll pass it to Nick. He'll comment more specifically around what we have there, and we have abstracts out. I think it's a -- again, a very exciting time as we debut and showcase some of the data that's coming out of our program. Obviously, KMT2A is approved. NPM1 is filed now with the FDA as an sNDA. And so that data, which we put out last year -- at the end of last year, and we'll be -- have an update here at EHA. But I think that data is extremely important. And now we're starting to, again, follow up and show more data in combination in newly diagnosed patients as well as relapsed/refractory patients. So we are starting to show the full, I'd say, opportunity with the profile in different settings. And as that data builds, I think it builds enthusiasm for Revuforj's utilization in the market today. So maybe, if you want to highlight some of the things at EHA?

Yes. No. I'm excited about EHA. We're going to have a really strong presence of that congress. We actually have 10 abstracts across the portfolio, including both Revuforj and Niktimvo, and we're going to be showcasing some really important data. I mean as a medical oncologist, there are probably a couple of things that I would call out that are, I think, going to be particularly impactful that we're looking forward to presenting. One is the Beat AML study. And this is a really important study because in collaboration with Beat AML, this is part of what I was talking about earlier, our transition into earlier lines of therapy, so specifically newly diagnosed patients in combination with standards of care therapy. So this is a Phase I/II study, looking at the combination of Revuforj with venetoclax and azacitidine for patients who are unfit for intensive chemotherapy. And there's a couple of important takeaways from this study. Number one is that we were able to combine the drug really very effectively and tolerably with standards of care, and that's really important for these patients. So specifically, we saw extremely low rates of Grade 3 differentiation syndrome or QTP. So it's easy to tolerate. We looked at 2 dose levels and were able to -- we didn't see a maximum tolerated dose. So importantly, again, and that was one of the intents of the study, we were able to confirm dose level 2 as the dose we've now taken into the confirmatory Phase III in collaboration with HOVON. And then on the background of that tolerability and confirmation of dose, we're seeing really encouraging -- it's a 43-patient study and across both dose levels. With a small study like that, what you really want to be focused on is how you're translating patients into complete responses. And we saw a very high, in the total population, a 67% complete response rate, which is really very high. Now just to contextualize that for everybody, the current standard of care from the off-quoted VIALE-A study is around 37% complete response rate. So when you see a response rate where you combine with Revuforj of 67%, that gives you a lot of confidence that you're really driving greater efficacy. And that's what physicians and patients want to see. They want to be driven into complete responses. And we saw a CRC rate or composite CR rate of 81%, which again is really very high compared to historical controls. The one other piece on the efficacy side I would just comment on is that you also want to look at MRD negativity. There's a big focus on that because then you know you're going to be getting really durable responses. And we had MRD evaluability in a high proportion of patients, 37. Remarkably, all 37 of those patients actually had MRD negative, most of them by the end of cycle 1. So that gives you really a lot of confidence that these patients are getting deep and durable responses, and that's going to translate very well into overall survival. So that's exciting. And then just one other abstract I'd highlight to you from the 10 we're going to have at EHA is the update to the AUGMENT-101 study. These are the data on which we have just submitted for an sNDA and have published in Blood. We're going to be presenting an update to those data, which is going to look at the total evaluable population we had in that study, which was 77 patients. And I think the reason that those data are important is we saw a CR/CRh of 26%, which is really, I think, quite compelling activity when you consider the benchmark for these patients historically has been somewhere of the order of 10%. So this is a step change. And we're looking forward to hopefully anticipating approval for that drug as an sNDA a little bit later in the year.

Well, great. I think that's a perfect segue to the next question, which is, obviously, Revuforj had a really strong first quarter. And so as you think of the drivers that got you there, was it prescriber base? Was it access? Can you talk a little bit about some of the mechanisms that you put in place there and really towards an eye of what we can expect sort of throughout the rest of the year?

Yes. Maybe, Steve, do you want to...

Yes, happy to, a great tee up, Jason. I think it's a lot of things that contribute to a successful launch and Revuforj is off to a successful launch. We had a great partial quarter in Q4 and really a recent quarter, which was fantastic. And it's all the things you mentioned. I mean, I think first and foremost, you want a foundation of users that is broad and deep. That is evolving quickly. We have provided an update in the March time frame about -- in February, we had 1/3 of what call Tier 1 and Tier 2 prescribers. This is 200 of the largest academic centers in the country, 1/3 had written by then by March, who was already up to 44%, and we can argue right now, it's at 50%. And as we move over the course of the year, that group is going to not only get bigger but get much deeper. So we're starting to see some key accounts use the drug in multiple patients. The other thing you mentioned is formulary coverage and payers, are they're willing to pay? And they are. I think part of this is because we engaged the payer community well in advance of approval. So we had stated in February, we're up to just over 50% formulary coverage, I think 72% in March. And I'd say right now, we'll provide an update probably at the next earnings call, but it's nearly complete. Payers are paying for the drug, which is great. I think they see the unmet need, they see the value in the drug. And the fact is they're seeing demand come in. There are some companies that won't even go through payers initially. They'll give away free drug. That wasn't our approach. And as formulary coverage has been evolving, claims have been paid, which is [ great. ] And the third part of this success, I'd argue, is getting patients on drug quickly. So we've got some great specialty pharmacy partners. We've got a great internal trade team and from the data we can see, we get 80% of patients on drug within a week. There's a substantial portion that get on within a couple of days. And that's important. As Michael said, these are very difficult, urgently sick patients and in some cases, days matter. So I think that has also been part of the success. And ultimately, it's about physician and patient experience. And the better experience that those groups have, the better we're able to build up competitive immunity. The bar is set very high for any potential compounds that may come after us. But -- and that foundation use will then lead towards other drivers, continued growth in new patients and refills, which we're already seeing, and we feel like we're on a great trajectory with a lot of upside for the rest of the year.

Got it. Well, that makes sense. Look, this is your first indication, and there's little doubt that this is a patient population with a lot of unmet need. But by that same token, it is rather a smaller segment of the overall population. In terms of overall opportunity and the trajectory for the KMT2A population, what should investors expect here?

Yes. Maybe I could start, and Steve can follow on. Look, this is -- what we know -- this is a KMT2A launch, right? So this is penetration of what we're seeing today in terms of sales and uptake and the vast majority of our new patient starts. So we believe this KMT2A launch is off to a great start. We think we'll penetrate a significant portion of the KMT2A population in the first year, call it 50%. So I think we're off to a good start, and I think we should assume that the vast majority of patients are KMT2A with other legs of build to come, right? So the second indication will be NPM1. We do believe we'll get into the guidelines this year ahead of approval towards the end of the year. And that could be a significant driver to additional new patient starts and penetration into that market. But I think this is a build between 2 indications. We are looking at benchmarks relative to other AML drugs that have launched in the past, targeted therapies. We are outpacing all of the benchmarks in terms of penetration, new patient starts, all of that. So we feel very confident that the growth will continue throughout the year and accelerate with the addition of NPM1, I think we could another -- take it to another level. So we are excited about what we're seeing and as Steve said, just putting all the pieces in place to make sure we get all the demand. There's really nothing standing in our way with KMT2A at this point as the approved indication to penetrate as much as we can.

Got it. And just a quick follow-up here. Obviously, last week, we saw the publication in Blood. What should we be thinking about in terms of when exactly the guidelines are updated? I know the committee is meeting relatively shortly, but again, sort of any possibility of an ad hoc meeting?

There is a possibility of an ad hoc meeting. I think the guideline meeting is coming up. And I think there's also -- for a new agent like this, new mechanism, groundbreaking data, first of its kind. This is an important drug. And I think physicians want to be able to use it in their practices, and guidelines help with that, right? So I think it's very important, as I said, step in the process of bringing this to market. And so yes, there's ad hoc means we've had ad hoc meetings for Revuforj for KMT2A, NPM1 -- I'm sorry, for Niktimvo, the approval, we got on guidelines at an off-cycle time as well. So it could be rather rapid, and it's up to them.

Perfect. So maybe switching gears now to the NPM1 mutant opportunity. So you've disclosed a CR/CRh rate of 23% in this population. Curious what sort of feedback you've received from the community and maybe how you would characterize interest and excitement. And then maybe as you think about physician familiarity with the drug and then levels of efficacy that you've evidenced, how does this position you to compete within this space?

Yes. Great question. Maybe I'll turn that over to Nick to talk a little bit about.

Yes. Let me just share a little bit of perspective on that. I mean, you're right around the 23%. But again, I would encourage us to look at the data we'll be presenting. You saw the abstract, which actually shows up 26%, I think, in the relevant population, which was the 77 patients we treated in that. So that's our sort of benchmark. And what we're hearing, and it's early days to me and the company, but what I've been hearing in my following of it is that physicians like the profile. I mean, I can't really speak to the kind of how it positions competitively because it's the only approved menin inhibitor in the market. It's the only available therapy. But in terms of the clinical use, what we're hearing from physicians is they like the profile. They're getting a lot of familiarity with it now. They're encouraged by the efficacy they've seen. We've commented previously that the older standards of care, they're not seeing a response rate even close to over 25% that we're now seeing with Revuforj. So that's encouraging. The drug is well managed. There are very clear guidelines in the label for how to monitor for ECGs, which is a standard thing. These patients are fairly hands on manage. They're quite sick. They have quite a lot of comorbidities. So it's a really very standard procedure in order to do some monitoring of ECG. So yes, we're encouraged by what we see. As I said, it's the only approved menin inhibitor on the market currently, and things seem to be going very well.

Great. So you recently submitted your sNDA in the population. When could we potentially see revenue come to market? And then given prior approval and lack of alternatives, maybe how quickly do you think regulators are willing to act? And then should we be expecting potential first-mover advantage in KMT2A?

I think yes to all your questions. I think in terms of rapidity, I mean, we're in a filing an sNDA. So this is a rather quick process to get the drug as a second indication to market. I think regulators are keen to bring it forward as a new class of agents for and make it available to all the patients that are applicable here, KMT2A, obviously, and now NPM1. And so I think they're moving and working with us very closely to enable that. We're under RTOR. So we submitted our application under RTOR, which allows for a rolling submission, and that's been -- it was completed in April. We'll, in a short period of time here, know where the PDUFA date lands. And we do know under RTOR that the timing for PDUFA is one measure of when you can come to market, but there have been examples, of course, of products being approved ahead of their PDUFA relative to RTOR, specifically for sNDA. So I think the advantage for us is we have a drug on the market, the agency just saw our package, right? This is the same review team. So they're very familiar with what they're looking at, and they're just looking at some new data now in NPM1. So I think we're well aligned to be first in that indication as well. And as I mentioned previously, we talk about guidelines. We talk about the fact that we will have perhaps in the guidelines this year ahead of -- even ahead of approval. So that could, of course, help with physician choice as they utilize Revuforj in the market. So I think it's a quick time frame to get the drug hopefully approved, and we're quite excited about that.

Maybe if we could focus now for a bit on the opportunity for Revu in combination with standard-of-care agents. For those who may not be as familiar, can you touch on the ongoing studies that are occurring both in the relapsed/refractory setting as well as in the front line? And then maybe highlight some of your near-term milestones and catalysts.

Yes. Sure. I'm excited about this. I have to say this is going to be a very important development. So just broadly, the way we're thinking about this, just for those less familiar with that is that when you think about treating patients in combination, particularly in newly diagnosed, you really want to think about patients that are fit and would get treated with intensive chemotherapy. And this is often patients with KMT2A mutations because giving them intensive therapy and then HSCT is their best chance for durable remission or even for cure. And then those -- there are those patients who are less fit. These tend to be slightly older patients over 60, 65 often with NPM1, who are going to get a ven/aza combination therapy if they're not considered fit for intensive chemotherapy. So that's the way we think about it. And how the market evolves in terms of the treatment of those 2 patients may evolve a little bit over time. Now we have -- we're very well placed. So you heard me talk earlier about the Beat AML trial. So that was the study that really informed the dose tolerability and indeed the efficacy we're seeing for those unfit patients who are getting the standard of care ven/aza. And collaborating with HOVON, we were the first company working with the HOVON Group to actually get a pivotal confirmatory Phase III study up and running. So that patient -- that study is now actively enrolling. We have first patient first visit. And it's going to be a large study. It's a multisite international study with really an ability, I think, to enroll quite quickly in this space. And that's where our focus has been. And that's -- the reason we prioritize out of the gate is because that's probably where there's the greatest unmet need and frankly, also where probably you're able to get an answer a little bit more quickly because those patients tend not to do so well, and we want to be able to impact that standard of care. And as we thought about the timing of that study, one of the endpoints we've always known was going to be very important in frontline AML is complete response rates. It's a well-established endpoint in AML. It's been used for previous approvals and is recognized in NCCN guidelines, et cetera. So we always had complete response and overall survival built into that study. But we have just recently through our engagement with health authorities included complete response rate as a dual primary end point. And the reason that's exciting is it just allows us to potentially able to answer that question for patients more quickly by looking at complete responses of surrogate whilst we wait for overall survival to read out with the potential to get an accelerated approval. And based on the data that I just shared with you from the Beat AML study that looked at complete response rates, it gives us quite a high degree of confidence that the combination is going to be better than the current standard of care, which is ven/aza alone. And then just very briefly, the other population of patients, which is a very high priority for us, and we are progressing in a very expedited way, is in combination with intensive chemotherapy, which is standardly so-called 7+3. And we have 2 ongoing studies to establish the dose and tolerability and demonstrate early efficacy, one of which is under Syndax sponsorship and one of which we're doing in collaboration with the NCI. We hope to have those data later this year, which will confirm the dose we're going to take into Phase III. And then as we have discussed, we have 2 randomized studies to confirm the benefit in frontline newly diagnosed patients for -- with intensive chemotherapy. And the way we're thinking about this is that acute myeloid leukemia is actually quite a heterogenous disease. It's heterogenous because of cytogenetics. It's heterogenous because there are a lot of prognostic factors. So we decided that we would actually do 2 randomized studies, one focused on KMT2A patients, which have different [ cycle ] expectations in treatment paradigm than those with NPM1 disease. So we're going to do 2 randomized studied looking at standard of care 7+3 plus revumenib, which we are hoping to have started in the latter part of this year, and that's certainly a priority for my team, and we're really looking forward to accelerating those studies.

Great. So you touched on prioritization. So just thinking about the overall maybe longer-term strategy from the combo setting, what partners do you think are most important? And how do you prioritize those in development in the future?

So in terms of partnerships, so -- well, I mean, we have a lot of partners in order to be successful with these studies. We're excited that we are leading with the unfit population and our collaboration with HOVON is going to be the key for that because they have this incredible network of international sites and their support is going to be key. But then there are lots of other partners we're going to have to work with to be successful. It's going to be a competitive space. That's the reality. And we want to continue to lead. I mean, Syndax has a history of a number of firsts in the development of menin inhibitors, and we want to maintain that. So we will be close -- working closely with a number of key institutions, thought leaders and in terms of community in order to be able to enroll to these studies well.

Yes. And I would just add on that I think in terms of maybe thinking about your question a little bit differently. All that being said, I think the work that we're doing with -- you think specifically about the drug combinations, ven/aza is going to be only, as Nick mentioned earlier, an expansion opportunity, I think as it sort of starts to maybe even encroach on the fit population. I think the physicians want to be able to use ven/aza in a variety of patients. And I think as that continues to grow, I think our work and being, obviously, first to get to market, hopefully, with that combination, we'll also build our utilization into other areas. So we're -- I think that's a very important combination for us. I think the -- in the fit population and how we work with chemo, obviously, as well. But I think the standard of care is evolving over time. So we think in terms of which agents we "partner with." That's, I think, an upside for us.

Maybe if I could add another kind of layer of complexity to an already complex question here. But as you think about regulatory support, there's sort of been a shift towards accelerated approval, both in fit and unfit disease. And curious, how does that factor into your decision-making process?

Yes. Look, I think, as I mentioned earlier, the agency is supportive of and then shown support in this particular disease for bringing new agents forward. They obviously weigh the risk benefit and make sure that they're the right agents to bring forward. But certainly, we've seen that this is not surrogate markers and using them for accelerated approval is not a new concept in this disease. Of course, CR has been used in the unfit population, thinking about ven/aza's approval there. So it's not a brand-new concept. The newer concept is on the unfit side of the equation, where you're using -- potentially using MRD-negative CR as an accelerated approval endpoint. And I think the agency has shown some willingness to talk about these things, and it's been going on for a long time. I think it's driven by physician desire, right? I think they feel they need agents to come to market more quickly that are efficacious for their patients and, and the ability to do that is being enabled by agency thoughtfulness around these endpoints. And so I don't think we see it as a major shift. We see it as a gradual shift and one that's enabled by great agents like Revuforj to be first and offer that up. So we're excited about what we're seeing. We'll embrace those endpoints as well. And we've seen -- as you've seen, we've incorporated CR into our regimen for the unfit population as an example.

On the brief time we have left, I did want to pivot quickly to Niktimvo. Obviously, very solid first quarter for it. As you think about sort of patient dynamics, are we dealing primarily with an early bolus of patients who are essentially out of options? Or is there much interest in kind of starting to move kind of broader in the paradigm?

Steve, do you want to take that?

Yes. It has been, and thanks for the comments. It's been a very, very good launch. I think your point about -- there are always available patients in the market. Patients with chronic GVHD are highly symptomatic. We know that there are patients prior to Niktimvo's approval that were ready for the next agent. So I think partly what we're seeing in the launches is that group of patients. There were some on EAP, which most have transitioned, there'll be more to come. I mean, I think -- also my example on Revuforj is relevant here, the base of transplant centers that have written virtually will say most, if not all, have already ordered, which is a very good start. But the early dynamics of this launch will -- it will take a few months really to play out. I think for us, it's what's that steady state. Things we're hearing early on about the product and its performance are very encouraging, partly because the product was approved in August. There were some EAP build and then the drug ultimately on market late January. So physicians already have a handle on how it's doing. So we're hearing great things about getting them on, very well tolerated. I think you can argue, I mean it will take a while for duration to play out, but this is the kind of drug patients can stay on. We're not talking months. We're talking years. So early days, very encouraged and a lot of upside.

Got it. And maybe just a final question here. When you think about the big drivers here, is it moving earlier in the paradigm? Or is it potentially moving outside GVHD into IPF?

Yes. Look, I think there's a lot of room to grow. And what we've seen so far is more of a fourth-line patient population in GVHD. And as Steve said, this is a very effective drug. Patients stay on potentially for years. So it's really turning this into a true chronic disease with a new mechanism of action, which differentiates us from others. But I do think growth beyond, and it can be a big business in third line, but I think it could be a very successful business beyond that north of $1 billion perhaps moving into frontline and having combination data will emerge over the next few years here. So I think that is a big opportunity in GVHD. But you mentioned other adjacencies. This drug has a really unique profile and the mechanism, and we're looking to deploy that into areas like IPF. So we have an ongoing trial there in 135 patients randomized trial. So this should give us a very good signal in IPF. We have really strong reasons to believe that this is going to be successful there as we've seen in GVHD patients who have lung disease tend to do very well on Niktimvo. So this is another area of growth that we're excited about, and there are potentially more that we're exploring as well with our partners. So we think it's a really good setup for this year and beyond for sure.

Well, great. We sadly are out of time, but I do want to thank you, Mike, Steve and Nick, for joining us. Appreciate it.

Thank you, Jason.

Thank you, Jason.