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

Welcome, everyone, to the, I believe, the last session of the first day of Citi's Biopharma Back-to-School Summit. I'm Yigal Nochomovitz, biotech analyst here at Citi. It's my pleasure to have with me senior management from Syndax Pharmaceuticals. Before we get started, if you have questions, just raise your hand and we can take questions from the audience, and welcome to everyone also listening on the webcast. And so of course, it's my pleasure to introduce Keith Goldan, CFO of Syndax; Steve Closter, CCO; and Nick Botwood, Head of Research and Development. So welcome all of you. Thank you so much for attending.

Keith, maybe you want to just give us a start. Obviously, you have 2 approved medicines now last year, 2 rapid approvals and succession. So if you could kind of just give us an overview of the commercial franchise and how those 2 launches, Revuforj and Niktimvo are going, that would be great.

Yes, sure. First of all, I want to thank Citi and Yigal. Thanks for having us. Great conference as always. So yes, it is a really exciting time at Syndax. As Yigal mentioned, we have 2 -- we're in the midst of 2 really great launches. We are outperforming, which is a good place to be. And I think it's really a testament to the unmet need that we're serving, both first-in-class products, Revuforj, targeting KMT2A translocated acute leukemia and Niktimvo, which is indicated for third-line cGVHD, chronic graft versus host disease. So both first-in-class products, we think best-in-class, like I said, targeting areas of really high unmet need. But I think that's really complemented by outstanding execution by this team here over the last 6 to 9 months. So both products, really long IP. We're funded to profitability. So it's a great story. And like I said, we're excited to be here.

Awesome. Okay. Well, let's get into a little bit of detail on Revuforj. This is the AML product. So you have the approval, obviously, in KMT2A. So can you just talk a bit about the growth drivers? You've had a few quarters now of sales. How is it looking? And what is the I don't know you've given guidance per se, but just in terms of just qualitatively, how -- what the momentum looks like? And of course, we'll talk about NPM1 as well in a moment.

Steve?

Yes, sure. It was a great quarter. I guess it was about a month ago, we announced earnings through Q2. So it was 43% growth in net sales. Q1 into Q2, we've generated over $50 million since the launch of the drug. We've finally started providing some metrics on the performance of the drug. We've been able to treat over 500 patients since the launch. This is through June. That's on top of about 1,300 prescriptions across that patient panel. And Yigal, I'd say there's 2 drivers to the performance right now. One is new patients, the other is really duration of treatment. So in terms of new patients, as mentioned, we've had 500 patients, KMT2Ar patients since launch. That's about 25% of what we consider the available market. We often talk about a TAM of about 2,000 incident patients. And I think to note, that's 2,000 new patients each and every year. Treating about 1/4 of them through June, we think, is a great accomplishment, but a lot of momentum, a lot of new patients being found that we'll expect by the end of the year. We'll treat over 50% of that population or about 1,000 patients. So we think it's a good start. The other piece to the puzzle is really average duration of treatment. So we've given previous guidance, and now we have data to confirm it. For this year, we would expect all patients on average to be on drug for about 4 to 6 months. That's those patients who perhaps didn't respond well versus those that were on drug for extended periods of time. Some dynamics that we're seeing in the marketplace that are really interesting. At the immediate launch, you saw much later line patients, much like we saw in the clinical trials. These were patients that were fourth or fifth line. In the most recent quarter, we've seen that migrate to much earlier line patients. So about 70% of patients will call either second line or third line and second line meaning first relapse. And likely, those patients, given that they're treated earlier, are going to do better, right? They have a better chance of treatment success and ultimately stay on drug for longer periods of time. So one of the dynamics that we see evolving is the percent of patients that go to transplant. It's about 1/3 from what we can tell from the data sources that we see and that comparison in the clinical trials was about 1/4. So we're performing better in the real world. That could go up even higher than that. We'll have to see what time tells us. But those patients are likely from transplant physicians tell us they want to go put patients back on as a restart on maintenance treatment. And that roughly takes about 90 to 120 days, and that's exactly where we are now. So the expectation is that we move into 2026, that average length of treatment will evolve from 4 to 6 months to 9 months. So those 2 things at play just give us a lot of confidence that we're really building a very good business and doing some great things for patients.

Okay. You made a lot of interesting and important points there. So the interesting point, you think from fourth to fifth line to moving to the second to third line, what do you attribute that to? Is that just getting your feet wet with some of the more sicker patients and then doctors getting more comfortable with earlier treatment? And then, of course, the question you could probably anticipate is of the transplant, the ones that go to the transplant, how many of those are coming back or do you know yet if they're coming back to Revuforj because that was something that was highlighted, I remember at ASH and many other times.

Yes. we can answer the first question. I'll give my view, and I think Nick probably has a view as a clinician on the movement. So I think pretty typical. You enter a market at a point in time and you have that range of patients, those that are newly diagnosed and those that are much later line. We heard of some patients coming off of hospice. So I think that's just a dynamic in the launch. But all along, I mean, as we were even developing Revuforj, physicians want to use it at first relapse. And that's exactly what they're doing. And part of it is finding patients and part of it is just using the drug and having some success. And that's what's led them to increasingly do that. And maybe I'll pause there if Nick has any comments.

No, they're all important points. And I would just add 2 things. One is that physicians like to treat earlier in disease. We're seeing that. We've presented a lot of data now for Revuforj in earlier lines of therapy, whether that be in combination or analyzed our data in the relapsed/refractory setting for those patients that have had less prior therapies and shown really quite compelling evidence. It's kind of typical as you treat earlier in a disease that you get better activity. And I think when patients have identified a KMT2A mutation to actually treat that with Revuforj is a compelling proposition. So they want to treat earlier. And when you treat earlier, you have a better chance of a response and you have a higher likelihood of going on to get a stem cell transplant, which particularly in the KMT2A population is really one of the ambitions of therapy. And the other thing that we've learned, talking with physicians across academic centers, thought leaders and also community doctors is given the precedent after stem cell transplant, you want to maintain those patients in remission. And their experience really dictates that many of those patients, they want to go back on to Revuforj to really maintain that remission after stem cell transplant. So even based on our experience in the clinical trials, we anticipate in clinical practice that more and more patients will, particularly if they have any evidence of minimal residual disease, either before the transplant or immediately after, want to go back on to Revuforj for maybe a year or 2 to really make sure they maintain that remission. That's the expectation of what we're going to see in terms of the treatment paradigm and what we're seeing in the clinic. We are -- the last point I'd make on this is we are working with a number of leading centers and planning registries actually to collect data in the real world of what the experience for patients are and hope to present some of those data later in this year, and that may shed some additional light on the patients that go back on to therapy after transplant.

Willing to give a preview, not the data itself, but the types of metrics that you would be collecting on that real-world evidence?

It's preliminary for now. But I think when we share those data back end of this year, early in 2026, we'll be able to show both the proportion of patients that actually go on to transplant and then those that go on to therapy subsequently. Too soon, I think, to share any insights from that data now, but we are in a unique position being the only approved menin inhibitor in the clinic with quite extensive use commercially now to be able to work with physicians and other health care providers to collect those data, which we're actively working to do and then present the data that look at those important parameters. So we're looking forward to presenting it, and I think it will be quite insightful when we do.

And Steve, you mentioned the 2,000 incident, and you mentioned climbing from the 25% now, which is already a very good start to 1,000. What's the -- to get that -- to close the gap to get to even above 1,000, what is required there? Is there another level of investment? Or is it just more market awareness, just more experience?

I would say it's just more time, and we've had enough time to understand how to work closely with treatment providers, and we've got a great customer-facing team that does that. So we've shown success from launch through June. We'll expect that to continue. It's been a robust stream of new patients coming on to trial. It's hard to predict exactly when the patients are coming in. It's not equal increments of 12 of the 2,000 patients every month. So it may go up and down, but we keep on course and keep executing, as Keith said, to find patients and make sure Revuforj is an option for them.

Okay. And Keith, of course, you have a very important FDA date coming up on...

October 25.

October 25. That was about to say. So tell us what that's for and why that's so significant for.

I'll let Steve talk about the commercial significance, but we do have an sNDA being reviewed by the agency under RTOR, real-time oncology review with a PDUFA date of, as you all said, October 25, a couple of weeks away. commercial opportunity.

Yes. So we're excited. The treatment community is excited and patients are certainly excited. For us, it's a big driver. We talked -- so far, we've talked about KMT2Ar patients. NPM1 certainly is another driver. That market is bigger than the KMT2A market. It's about 4,500 patients versus the 2,000. The patients are a little different. They tend to be a little bit older, more Medicare coverage, fewer of them go to transplant. But I think as an organization, we're excited because the same treaters that we've been calling on treating and finding KMT2Ar patients are the same treaters that will find NPM1 patients. So we've got a leg up. We take competitive immunity seriously and first-mover advantage and having the ability to share Revuforj and the opportunity for current treaters by the time we hit our PDUFA date. And if, in fact, there is another men in the market, you'll have well over 1,000 patients that have been treated on Revuforj. And that's meaningful. To gain some muscle memory with a treatment center is important. It's not just physicians. It's their staff, it's the nursing staff, it's pathology, it's formulary, it's how do they access the drug. So that's a lot of experience. And Yigal often it takes not a lot for physicians to gain experience and some loyalty with the drug. Typically, they'll say it's 2 to 3 patients. So for many of the providers out there, they'll be in that window. So we are really optimistic and excited about the launch of NPM1. The space possibly will be competitive, and we're more than ready for that.

And just for those less -- a little bit less familiar, can you just summarize the pivotal data that supports NPM1?

Yes, I would be happy to. These are data from our AUGMENT-101 study in NPM1. So this was a series of patients with a primary endpoint of CR/CRh, and we reported 26% of that in the enlarged Phase II cohort of around 77 patients. I think perhaps even more important than CR/CRh is when you look at the overall response rate. That's really the endpoint physicians are most interested in because if you can get these patients into response, it gives them the highest probability of them potentially going on to get a stem cell transplant. We reported 48% overall response rate in these patients. That's really quite unprecedented for nearly half of the patients to have a response. We're really very excited about that. Importantly, the durability of that is also key. So we did an exploratory analysis looking at overall survival in those patients that respond and the nearly half of patients to respond and found the median overall survival to be 23 months, so nearly 2 years, which, again, in a setting where traditionally the expectations of survival for patients with relapsed/refractory AML is of the order of 2 to 3 months. This is an enormous change in the potential standard of care. And that was also coupled -- again, I focus on efficacy because these are very unwell patients where you really want to focus on efficacy, but I think that's also coupled with a very predictable and well-established tolerability profile. Very few patients had to have any form of dose reduction or dose interruption as a result of toxicity. It's a very manageable safety profile and physicians are now familiar with it from our experience with KMT2A. So it's a compelling profile. We believe it's a best-in-class profile and looking forward to the upcoming PDUFA.

So October 25, so Steve, the ramp for NPM1, how do you see that? I mean you already have the drug in the market and people are already using it, and they're probably either maybe using a little bit off label or very much wanting to use it. So is the ramp going to be the same? Or is it going to be steeper for NPM1? And -- but you do have a competitor coming possibly a month later. So there's different pushes and pulls there.

There are. I think the market is primed. I mean they know about the compound. There is, as mentioned, some off-label use. Obviously, we don't promote there, but about 10% of the use is outside of the approved indication. So there's some experience. We haven't commented on ramp, but the drug is available. It's there. The education is high. The awareness is high. The NPM1 data was published in blood peer-reviewed journal back in May. So the interest level will be there. So I would expect some pretty rapid uptake. I think as it relates to a competitive space, I may reiterate some of the things Nick has said. This is a market that's really built on efficacy. Physicians want to use the drug that's going to work best. These patients are very much at risk. Second thing I'd point out is physicians like to use drugs that have multiple indications, and we'll be the only menin on market, assuming the next one makes it that has 2 indications. So it's broader. It will treat up to roughly 50% of the population. It's going to be adults in pediatrics, AML and ALL and all of that is very attractive. And the third point I make is just the experience that they have with us, drug and channel, positive experiences with Revuforj. That's going to be, I think, challenging for a competitor to overcome that. So we remain optimistic on the launch.

So of course, those 2 relapsed/refractory markets, the KMT2A and the NPM1, that's adding it up, it's 6,500 or so incident, but that's just the start. I'd love to hear more about the earlier studies. There's 2. There's BEAT AML, the SAVE AML that are going to try to advance into earlier lines of therapy. So -- and I'd love to understand the market for that as well as the design of the studies and what you're going to show, I believe there will be more data coming at ASH on both of those.

Yes. So from a market perspective, it really opens up the opportunity. We've often talked about the relapsed/refractory market is just over $2 billion in potential between the 2 indications. But overall, when you include frontline, it's really a $5 billion opportunity. So it's roughly about 9,000 patients that would be affected frontline for KMT2A as well as NPM1. Duration of treatment is going to be on the longer side. Patients are just earlier in their disease therapy. And at the current price point, that's how you get a TAM that's as large as that.

Maybe, Nick, do you want to comment a little on what the study...

I would be happy to, and we're excited to be leading in this space. As leaders in the class, we were the first to have a patient enrolled in the frontline setting in a Phase III study. This is a study that we have ongoing in collaboration with the HOVON group. This is a well-established collaborative group that we're working with for the combination with venetoclax and azathioprine. This is for patients who are unfit for intensive chemotherapy. And the premise for this study was really based on the BEAT AML data that was presented at EHA this year that really showed compelling activity when you combine revumenib with ven/aza in terms of the CR rate, but also importantly, the MRD negativity rate. We reported 100% of the patients, so 37 out of 37 patients had MRD negativity and a really compelling efficacy profile combined with a very tolerable combination regimen at the standard approved dose of [ 160/270 ]. So those data are very supportive of the Phase III study we have ongoing with -- in collaboration with HOVON, and we will be updating those data in due course. It's a BEAT AML-sponsored study. The study is continuing to enroll. So there will be more patients in that study in due course, and we will update some of those efficacy endpoints, but it was a compelling profile. In addition to that, we have 2 planned studies combined with intensive chemotherapy. We're thinking about this such that we have one study focused on patients that have KMT2A relocated AML and one for NPM1 mutated AML. We will be presenting later this year Phase Ib data that establishes a tolerable dose in combination with intensive chemotherapy. That study is progressing well. And also preliminary efficacy that we're anticipating will be very supportive of those 2 Phase III settings we have with intensive chemotherapy in the frontline setting. Those are, I believe, very smartly designed studies. We're really driving some innovation in this space as leaders in the menin field. We'll reveal more about the designs of those studies later this year, but I think they are very well designed. They have the potential for accelerated approval using early surrogate endpoints. We think that's exciting because that gives us the opportunity to bring combination therapy to patients earlier in the frontline or newly diagnosed setting. And as I say, we're hoping to have those studies enrolling and they'll enroll competitively based on the data we presented. And we think we can continue to lead in that space. So it's a very exciting part of our life cycle management plans, and it's a priority for us.

And that would be something on the lines of like a minimal residual disease, MRD negativity type surrogate.

It would. In the ven/aza unfit, complete response is a well-established surrogate for these patients. It's been used before for regulatory approvals and is in guidelines. So we've built complete response rate in as a dual primary endpoint in collaboration with the HOVON study, and that would certainly serve as a potential surrogate to support accelerated approval with -- in combination with intensive chemotherapy, the so-called 7+3 regimen for NPM1 patients, we're actually looking at MRD-negative CR. We think that could be a more sensitive and more accurate predictor for correlating with event-free survival and OS subsequently. So our dual primary endpoint there is based on MRD-negative CR. And we think that if we can show a sizable difference over the current benchmarks, which trend around 40% if you look at MRD-negative CR. So clearly, a high unmet need remains in those patients even getting treated with intensive chemotherapy. If we can add to that with the addition of Revuforj, we believe that, that could also serve as a potential for accelerated approval in due course. And that's something that we have built into the Phase III.

And how are things shaping up competitively because there are obviously other companies that are pushing in frontline as well in combination with some of the similar regimens you described. How is it shaking out as far as getting to market in frontline, if you have estimates for that?

Yes, we feel very confident. We have a well-established profile and a well-established support and advocacy for the programs. We presented, I think, compelling data from BEAT AML. And as I say, we'll be presenting more data in the latter part of this year that will support those Phase III programs. The designs have been supported by the best academic thought leaders working really closely with leading sites and centers. We think they're well-designed studies. And we think that working with our partners across the spectrum, those studies will be very competitive and recruit well. And our expectation is to continue to lead in this space.

Okay. Maybe we could switch gears a little bit and talk about GVHD. So of course, there, you're partnered with Incyte, which I'm sure is helping. So just can you kind of characterize the launch? It's been strong from what I gather. So tell us about the dynamics, and that's in the third line. But similarly, thematically to AML, you're also starting to move into the earlier lines. So it's kind of a different drug, but same concept.