All right. Well, welcome, Michael from Syndax here with me. I really appreciate you taking the time this afternoon. You're closing out my track at the conference here, so let's finish strong.
Will do.
It's been a busy year for you guys. Three approvals across two drugs. Launches seem like they're going quite well. So let's start with you. What are you looking forward to in 2026?
Yeah. Well, thanks, first of all, thank you for having us. It's been great to be here in Florida. I think this is a really important time for Syndax. The year has been fantastic in terms of two launches. As you mentioned, products are off to a fantastic start. One is, of course, Revuforj, which is indicated now. Second indication, recently approved for NPM1, was previously approved for just KMT2A, the broadest label across patient types, now approaching about 50% of the patient population in acute leukemia. So again, relapsed/refractory, KMT2A, NPM1, AML, ALL, adults, pediatrics, really just a wonderful place to be at this time of the year. And the product is really doing well from a commercial standpoint. Physicians really like the profile, and they're looking forward to using it at a new indication. So we've had a good year.
We expect to have a good fourth quarter. And obviously, next year is going to be very strong as well as we look into building the second launch through NPM1 and then doing all the work that we're doing to get to frontline. And then, of course, the second product, Niktimvo for chronic GVHD, another really strong launch, I think, between both products, really resetting industry benchmarks for performance. This one is chronic GVHD, third line plus, indicated new mechanism of action, CSF1R inhibitor. And that drug offers something new to patients as well, giving them both anti-fibrotic and anti-inflammatory mechanism of action that can really help improve their symptomology and give them something to work with for perhaps many years. And so this is, again, chronic therapy for patients who have limited options at this point.
So we're very excited to see how both drugs continue to be used as monotherapy, potentially as combination therapy. We have lots of data, and this is what we're looking forward to, lots of data coming out, real-world data as well as clinical trial data that demonstrate the breadth of opportunity for both agents. And again, we're approved and just getting started, but we have a lot more to do and build tremendous franchises.
Excellent. Let's start with the menin and AML. Obviously, you've been launching here for a little bit over a year in the first indication. And as you mentioned, the launch seems to be setting new benchmarks in the indication, very rapid. Can you speak to why the launch has been driven so rapidly? What's helping you with speed of adoption?
Yeah. So this is an indication. So the first indication that we approved for Revuforj was KMT2A, which affects mostly younger patients, not only younger patients, but it skews a little bit younger relative to overall AML. And these patients have really nothing for them. So standard of care does not work particularly well. Chemotherapy and other therapies that may be available for these patients, they don't work particularly well. So this is a patient with high unmet medical need, about 2,000 patients. And really, they were looking for something for them. This is the first drug of its kind to be indicated for KMT2A. It spans both kids all the way up to adults. So we can give it to the broadest breadth of patients. And so what's driving this is really unmet need and a great product. This is a product that patients can take.
It's oral twice a day. They can take it, get to remission very quickly, usually within the first month or two. They're getting to a deep and durable response. The paradigm here is to get patients, because they are young, to as many transplants as they can accomplish in this population. It's typical third line, third, fourth line. They're getting about 5% of the patients are getting transplanted, which is not very good. Now with our drug, we're in the 30% range in terms of transplants. That is really an important sea change. So physicians are excited about deep, durable, fast responses, being able to get them to transplant. And then ultimately, once they go through a transplant, put them back on drug. And we're seeing that as well. And I think all of those factors, being able to treat them well, treat them early, right?
So you're not waiting till their third, fourth line anymore. You're doing it second line, maybe third line. You're getting them to a place where they can benefit from treatment and then keeping them on drug a long time. That's the paradigm that they always want for these types of patients. And our drug is the first to be able to deliver for KMT2A patients in that regard. So we're just really excited about, and it's now starting to show manifest in terms of sales numbers. And that's what we're seeing build throughout the year.
Let's talk about that transplant paradigm that you were just talking about. You said 5% maybe historically would be the number you're getting up into the 30s. Can you walk us through maybe in some granularity the difference between the historical numbers, your trial numbers, and what you're seeing now in a commercial setting?
Right. So I mentioned the 5% third line is the historic benchmark in that range, maybe less than 5%, 4%, 5% patients getting to transplant once they've gone through the initial.
Do you know what that number is in the second line?
It's a little higher. It's probably in the 30%-40% range.
Okay. So there is a pretty substantial drop-off as you're getting down.
Yeah. Usually, they're not getting transplanted again. They usually get a transplant if they can get to one in the first setting. But 80% of the patients fail frontline setting. So you're seeing most of those patients kind of drop down. So we are, I think, changing the way this disease is treated. When you get to our clinical trial, which is our pivotal trial, about 25% on an ITT basis, that number of patients transplanted of overall patients.
That was a mixed population?
It was AML and ALL, yes. So we're talking about KMT2A patients overall.
Across the board.
Yeah. And again, pediatrics and adults. And so that was a historic benchmark, right? Getting to that level was eye-opening for physicians. And I think they were keenly aware of the need to bring them to transplant, but they didn't have a medicine that could accomplish that. And now we move into the commercial setting, and we're seeing that go higher. That's now at about a third. People have asked, how high could it go? Who knows? But it could be 50%, could be higher than that. And we expect that physicians will continue to push that as they move patients up.
So the driver there is getting to second line, getting to a greater proportion of patients in the earlier line.
Yeah. W hat we've heard from physicians, it's, can you treat them earlier? And of course, you can. This is relapsed/refractory. So after they've failed one therapy, they can come on. It's on label. They can come on therapy. And so that is what we're trying to accomplish.
Yeah. Now, you mentioned something very interesting about getting patients back onto therapy after transplant, being a driver for duration of therapy and potentially keeping people on drug for quite a while. And that dovetails with the question that I have about penetration into KMT2A in particular. It feels like you've got a fair proportion of the incidence population already, a lot of enthusiasm coming onto the drug. So can we talk about growth prospects and what drives growth in the KMT2A setting in particular from here?
Sure. So you alluded to it. The penetration of KMT2A, it's a market we should dominate. We should own this market. Utilization so far has been very good. We've said by the end of this year, we'll be about 50% penetrated on an incidence population of about 2,000 patients. So again, that refreshes every year, of course. And we will continue to penetrate that. How high could that go? It could be 90%, 80%, 90%. W e've seen that with EGFR inhibitors and other targeted therapies.
You should be standard of care. You should be getting just about everybody who can tolerate it.
I think we're quickly becoming standard of care. So that is an important area of growth. You think about patients coming back from transplant, and they go back on maintenance therapy. Physicians have told us over and over again that this is what they expect to do for patients. Very high percentage will have maintenance therapy that are KMT2A.
What does a very high percentage mean?
It could be 70%, 80%, 90%. I t's the consistency that we hear the same remarks from physicians that that's what they intend to do. They intend to put them on maintenance. And they're starting to do that. You see that in the real-world experience and where we have 35%-40% of patients going back on maintenance now. That should grow. That should grow. And I mentioned 70%-90%. It could be as high as that. And that's the goal.
Duration of maintenance relative to induction?
We've seen patients stay on for three years. So patients have done really well in the maintenance setting. We'll have some data at ASH this year that speaks to the pediatric patients taking extended maintenance. We have real-world experience that's building across adults and pediatrics. We've seen it in our Augment 101 trial, patients going back on and continuing on therapy. So physicians tell us two years of maintenance is something that they would consider. That's what they're considering. And we've seen it in the trial experience as well as now we're getting it in real world where patients can stay on and do very well, meaning they stay in remission, they're able to tolerate the therapy, and they can live their lives. That's a very different value proposition, obviously, for these types of patients.
But also from an incidence population perspective of 2,000, now you're potentially growing that far beyond.
Yes.
Not just to a prevalence population, but with multi-year duration of therapy, you're going to.
Correct. So we'll continue to penetrate this population. That's a driver. We will put patients back on maintenance and continue on. And those patients will stack over time. That's why we think this market can be very, very substantial, especially because we will be the standard of care and dominate this market for many years.
Excellent. Let's turn to NPM1 now, where you've said you have a running start because all the same docs have experience with this drug now. Can you talk a little bit about how that's been evolving since the recent launch?
Running start. Physicians, we were excited about the fact that we were able to get guidelines before the approval, which gave us a little bit of an advantage. Physicians practice to guidelines. They tend to look at that as something that is important for their overall treatment. And what we've seen in the first year, we had about 10% of the patients were NPM1 patients. It's 90% KMT2A and about 10% NPM1. So physicians have already had experience using the drug, which is fantastic. Now they got guidelines, and then they got the approval about a month later. So that's enabled us to really get the message out. We have a field medical team as well as a full commercial team that has the ability to utilize the guidelines, utilize the label. And so we are calling on the whole universe of physicians, about 2,000 physicians.
The treatments are done both in the academic centers as well as in the community. We're able to cover everybody, and we've seen an uptick in script activity this quarter. We've also seen new users, right? Physicians actually writing for the first time, and they're writing for KMT2A, and they're writing for NPM1, but I think it's really about having the breadth of commercial and medical teams out there with the label and being able to talk about all the data that we're generating real-world and some of the things at ASH that you'll see really helps physicians understand how best to utilize the drug.
Excellent. Excellent. You're obviously running first-line trials too. Can we talk a little bit about the potential to move up and broaden the label even further?
We're very keen to get to the front line and be the first to get there. We do believe that that is not only possible, but pretty certain. We've already started our trials. We have two different populations of patients. You have the unfit population and the fit population. Unfit is served by Ven-Aza as standard of care in the front line. We'll be combining with Ven/Aza. We are running that trial. We're already standing up sites, enrolling patients. So that's underway and doing well. We've also started our fit trial, which is chemotherapy 7+3 plus Revuforj. That trial has initiated, and we'll have some data at ASH talking about 7 + 3 plus Revuforj are the first data to be shown and how that looks like. Based on the abstracts, it looks quite promising, as we would expect.
And so physicians are excited to get started with that trial too. So two pivotal trials. And based on what we expect, we'll be there first.
Maybe let's talk about the Ven-Aza combo first for just a second. This is obviously an unfit population, as you say. Ven-Aza has its own challenges. What should we be looking for in terms of the differentiating in terms of differentiation in the early data?
Right.
Is it really an efficacy story? Is there enough safety to dose appropriately? That's sort of what I'm asking.
Right. So I think the benefit that we have, not only are we starting a pivotal trial for the first time, but we've generated in collaboration with Beat AML specifically for that population, the largest data set. So the largest data set in combination with Ven/Aza. We're talking now, they're enrolling more patients. So it's somewhere between 50 and 100 patients at this point. So a lot of patient data. That data is continuing to emerge. Not only do we have efficacy data, but safety data. And it looks like we're not adding any significant toxicity to the standard of care. That's point number one. Point number two, efficacy is a sea change versus what they've seen with Ven/Aza. We're talking about CR rates in the 70% range, whereas Ven/Aza alone is in the 30% range. Yeah, it's low relative to what we've seen.
We see MRD rates for Ven/Aza in the 20%-20% range, 20%-25% range. We're at close to 100%, if not 100%. So we're changing the efficacy profile by adding an agent without taking away from safety. And that is extremely promising. More data to come. Having a pivotal trial there and being first to that market is going to be very significant. Ven/Aza is a really important regimen. It's showing to be important not only for patients who are unfit for chemo, but potentially for patients who are fit for chemo. And we'll see some data on that at ASH this year. It could be very important. But that is really the future of AML treatment. We believe that that regimen is extremely important to keep your eye on. So we're going to absolutely be first and front line there.
And then with 7 + 3, we also think we can make a major difference. And that trial is, again, on top of standard of care, 7 + 3.
So obviously a lot going on here. I want to make sure we have some time to talk about GVHD. But just before we get there, can you walk me through maybe pretty granularly? You have a bunch of stuff coming at ASH.
We do.
And you also have multiple catalysts over the next 12, 18 months as we look forward to 2026. Can we just go through the list so I have it in my head?
Sure. So lots of data. We have 23 presentations at ASH this year, which is a dizzying amount. But it's going to be great. It's pretty much half and half between Revuforj and Niktimvo, and we'll get to Niktimvo. But the breadth of data spans, I would say, real world, which is the first real world studies, both for maintenance as well as you'll see a lot of combination data at the Moffitt study looking at KMT2A, NPM1. What does the efficacy look like? What does the safety look like? What does the maintenance look like? Patients are going on maintenance. Some patients haven't even received Revuforj before transplant. We're starting to see some of that.
Not initial adoption at that point.
Initial adoption, yeah, in the post-transplant setting so you're seeing the breadth of data. You're also going to see 7 + 3, as I mentioned, the phase one data, two different trials, one from NCI and one from us, help understand that profile a little bit better so I think you're getting the breadth of data around the profile, which helps elucidate for physicians.
It's very rapid expansion.
Very rapid expansion and then when you think about Niktimvo, you want milestones, sorry. That was the next question in terms of our milestones. Look, I think this is a sales execution and development timeframe for us where we have sales will continue to ramp. We expect this to be a rapid adoption and we look to dominate both KMT2A and NPM1 in the relapsed/refractory setting. I think we're off to a fantastic start. That will continue, and we'll report on that as time goes on, so those are always important milestones. The other aspect of this is development and we have pivotal trials enrolling. We have combination trials. There are many ISTs and things that would look at combinations with FLT3 and other combinations that will come down the pike. We'll also have real-world data, which, again, we'll continue to build and help support the brand.
That data will be mixed throughout the entire year. So you'll see lots of clinical.
Continuous set of catalysts.
Exactly. So it's hard to pinpoint one. There are many.
Excellent. That's a great thing to hear always.
Yes. And then do you want?
Let's talk about GVHD. I want to make sure we have a chance to. This is a place where you also seem to be launching very well, especially considering the competitor launched a little bit ahead of you. So can you talk a little bit about what the commercial dynamic is in GVHD right now?
Yeah, it's very interesting. Usually, you think of order of entry.
Very important.
Right. Same third-line plus GVHD indication that our competitor, Sanofi's product, Rezurock, received, and they did start ahead of us. We're tracking sort of right on line with them, and they've done very well, about $550 million in third-year sales. We're tracking right there with them. I would say we're actually doing better. Usually, in an order of entry, you're a log different, right? You're a step down, but we've actually done just as well, maybe even better, so to us, it's sort of a low watermark for where we could take this market. Now, this is about 6,500 patients, third-line plus. We're building the business today in fourth-line and starting to penetrate into third-line and taking share, we believe, from our competitor in the third-line. There's the opportunity, of course, to combine this agent with Jakafi or steroids.
We're running those trials now. And that expands the population to 15,000 to 17,000 patients in the US. So quite a bit larger. The best opportunity that I can say about this drug is the ability to not only get them to deep, durable responses, but to keep them there. It's sort of a similar concept to what you have with Revuforj. But this is, I would say, patients are staying on this drug for a long time.
Is it too soon to say what duration of therapy could be in the real world? O bviously, this is something where we expect it to be quite long in the real world.
Multiple years. It's quite possible. We've seen that in the data. And you'll see this at ASH. There's a presentation there where you follow up from our Agave trial, where patients have stayed on for almost three years. And we know the persistency from launch has been very high. 80-plus% of the patients are staying on therapy from launch. Incredible result.
That's quite a remarkable result.
It's quite a remarkable result. And look, they're getting to responses very quickly. And we're talking about efficacy that hasn't been seen in this category. We're treating the sickest patients, average fourth line patients. And they're getting to response and staying in response for not months, but years. A phenomenal result. And so that's how you build the market. You build the market at monotherapy from the ground up. And then you add on, you layer on some of these other therapies so they can stay on therapy even longer and do even better. So that's the game plan. That's how we're taking it.
That makes perfect sense. In our last moment here, can we talk a little bit about the path to profitability and what needs to go right in order to achieve a sustainable, profitable profile?
Sure.
Full steam ahead.
Full steam ahead. The products need to continue to contribute. We think they will grow significantly from here. Both products can contribute meaningfully to our cash flow and we have $456 million in the last quarter in cash, which with our priorities, which is development around the front line trials and some of these combinations and the contributions of the two products from a revenue perspective, we think we can get the profitability based on what we have and that's where we're driving. There's really no doubt about it.
I ask because consensus seems to be pretty variable here, certainly quite variable in modeling the evolution of revenues from here, variable in terms of the likelihood of getting to profitability. So what are folks missing? It seems like you're launching well. You've got all these irons on the fire from the development perspective. What is it that consensus isn't appreciating?
I think they are getting it. I t's starting to.
It's starting to percolate.
Yeah, they're starting to percolate. I think this concept of cash flow break-even and profitability and the priorities, and we've been very focused in telling people what our priorities are and how we are going to spend our money, that is now coming into focus for a lot of the analysts. The trajectory of revenue and the contribution from both products, but also Niktimvo, and maybe that's a piece of what people have missed. It's a very profitable product, very focused call point. We're calling on the same audience for two products. It's very unusual for a small company to be able to do that. And the efficiency of doing that with very high margin drives us quickly to profitability. And maybe that's why people are missing it, because they don't see this very often. It's an unusual situation.
That synergy.
Efficiency and the synergy is there, yes.
Limited call. That makes perfect sense to me. Thank you so much. Mike, this is incredible to have you here.
Thank you.
What a year for Syndax and looking forward to everything you're going to do in 2026.
Thanks so much. Great to be here.