Good afternoon and welcome once again to TD Cowen's 46th Annual Healthcare conference. I'm Phil Nadeau, one of the Biotech Analysts here at Cowen. It's my pleasure to moderate a fireside chat with Syndax. We have with us Michael Metzger, the CEO, and Keith Goldan, CFO. Guys, I'll kick it over to you to begin. Can you give us a state of the company overview, where's Syndax today, your biggest strengths, biggest challenges, and how are you gonna create shareholder value?
Phil. Yeah, thank you. First of all, good to see everybody. Thank you, Phil, for having us, TD Cowen, great conference to be at. We are in a very good position as a company. Many of you know our story. Two now commercial products in, within the heme space, one for acute AML, the other for chronic GVHD. After about a year of sales on the market, have, you know, really reset benchmarks for these diseases in terms of patients treated, as well as revenue, and we can talk about all that. Certainly off to a fantastic start. Two approvals, actually three approvals in about a year's time, which is an exciting time for our company when you build a new set of indications and bring the product to market, for the first time.
We've done that with excellence. We recently reviewed our quarter. I'm sure we'll have some questions about that for fourth quarter and for full year revenue. We've had a tremendous start with a recent new indication that came on NPM1 for Revuforj and that's off to a great start. We've built the capability to broadly bring the product to market. Formulary coverage is extremely high, and so we are now really in a great position to get to the next level and launch the drug. First of all, get data, and then eventually launch the drug in new indications, frontline indications, where the total addressable market is upwards of $10 billion for both products combined.
We are, you know, I think as an organization, well-built, well-scaled to do everything we need to do, have the cash we need in order to reach profitability, within the next horizon here. New indications and with data coming in within the pipeline, really sets up a wonderful year of 2026 for both products to expand and to grow. As far as, challenges, All companies always have challenges, but I think we're as well positioned as any to achieve and get where we need to get to.
Maybe to dive into Revuforj in the fourth quarter, in particular, you reported $44 million in revenue with 1,150 total prescriptions. Give us some sense of the trajectory of the launch today with strata of KMT2A versus NPM1?
KMT2A, NPM1 are the two indications were approved in adults and pediatrics. Again, this is Revuforj. Last quarter, $44 million. For the full year, $125 million of revenue, which, as I mentioned, is more than any company has ever achieved in its first-year sales for an AML product. The launch is really predicated on these two indications. First indication is KMT2A, which was the primary driver of business in the first year, where we have new patient starts approaching about 50% of the market, about 2,000 patients, total addressable market, and we are approaching about 50% penetrated in its first full year. As we steadily add patients, that's a driver of growth in the first year and will be a driver going forward.
Then there's, of course, the phenomenon where patients go to transplant, our ability to get patients to a potentially life-saving transplant. Then once they go through their transplant, they come back on Revuforj in the post-transplant maintenance setting. We've talked about how that has continued to stack over time. You start to see more patients come back. In this quarter, the fourth quarter, we had about 40%-45% of our patients who went to transplant come back and go back on Revuforj, which is a very good sign of growth. We expect that to be a, you know, a very significant driver going into 2026 and beyond for that indication.
Of course, we had about 10% of the business in the first half of the year or so was NPM1 off-label before we got the indication. In the third quarter, we were included in the guidelines based on our pivotal trial. That business grew to about 20% through the third quarter based on guidelines and based on momentum. Of course, fourth quarter, we got the approval, and that business has been now about 30%+ new patient starts NPM1. That business continues to track as we've gone from sort of 10%-30%+ in the fourth quarter. We're off to a great start in the first quarter of this year. Momentum continues to build.
We expect both will be a driver for growth going forward here for NPM1 and KMT2A, as I mentioned, together will should be quite the dominant force within KMT2A and NPM within relapsed refractory for many years.
Consensus for Q1 looks to be $51 million, and for all of 2026, approximately $300 million, maybe a little bit less. I guess first, does that actually accurately reflect investor expectations based on your conversations? Then two, how do you feel about those numbers?
Keith.
Since we don't currently give revenue guidance, not gonna specifically comment on the consensus numbers. Although I will say, based on the research that we've done, whether you're looking at FactSet, VA, Bloomberg, no more than about six or seven of our 14 covered analysts are covered by any one of those three organizations. What we've done is worked with Vara Research. You can access their consensus numbers on our website in the investor relations section. What we've done, what Sharon has done, our head of IR, is set up conduits between all 14 covering analysts and Vara so that all 14 models get uploaded. That is the only consensus reporting that we know captures 100% of all the research that's done.
Great. I think Keith, or actually Michael, you mentioned that growth is gonna be driven by increasing duration of therapy in 2026 post-maintenance, post-transplant maintenance. Can you discuss a little bit more where duration of therapy is today, where it could go, and what's driving that?
What's very important for any of these populations, but certainly for KMT2A and NPM1, is the ability to treat patients earlier and earlier. That allows you to access more of the patients, certainly. We know that the earlier you treat patients, the better they do, the longer they stay on therapy. That's, you know, essentially what we're driving for. In the first year, we had said that duration of therapy, across the treated population would be roughly 4-6 months, and that factors in very few of the patients who are coming back from transplant to go back on maintenance therapy. We recognize that as the year went on, you give more time, more patients would come back, and we're starting to see that.
The first year we were certainly within that, solidly within that 4-6 month range. We expect with more patients returning from transplant, more patients going to transplant, but certainly more patients coming back from transplant, as well as the addition of the NPM1 patients who will also receive transplants, but fewer transplants. They definitely are of an older population, so they don't get transplanted as often, but when they do, they tend to get back on maintenance as well. I think the mix of patients we should see in the second year, 6-12 months elongation to our days of time on therapy or days of therapy.
That's a healthy, I think, a healthy driver of business as we look again to stack patients month after month on therapy and maintain them in remission.
What is Syndax's most recent estimate for the total market size in relapsed refractory disease? Can you give us some idea of how you get there in terms of duration of therapy, market share, overall penetration?
Sure. I think we've been pretty consistent here. The total addressable market for relapsed refractory, again, both buckets. KMT2A, about 2,000 addressable patients, for NPM1 is about 4,500 addressable patients. Price for the drug is somewhere between $45,000-$50,000 a month. I'm doing the math for you. Then we get to days on therapy, which is the bigger variable here. We talk about 4-6 months across the population, year one, 6-12 the second. But you have to break it down a little bit more specifically. When you think about KMT2A patients, there are some patients who naturally won't respond, but vast majority of patients will respond and get through, get to, you know, durable response.
A good portion of those patients go on to transplant, and then a portion of those patients come back for maintenance. Now, maintenance is for most physicians in the year to one to two-year timeframe. They'll put patients back on and keep them there for that amount of time. If you think about the different types of patients that are KMT2A, including a maintenance of one to two years, it's roughly, we say about nine months. We're estimating about nine months of therapy at maturity. Could it be longer than that for any given patient? Of course. It could also be shorter. Take nine months as a reasonable estimate.
If you do the math, nine months, 45,000-50,000 times 2,000 patients, you're at about, you know, $750 million in a total addressable market. Do the same math for NPM1 with a duration somewhere 6-9 months, fewer transplanted patients, so you'll have slightly shorter duration. You should come out to about $1.2 billion-$1.4 billion in market opportunity, something in that range. Together, $2 billion-plus in total addressable market, which of course, when you get to the front line, you have to think about that as and I'm probably anticipating one of your questions, bigger market opportunity in the sense that there are about 9,000 patients between the two, the unfit patients and the fit patients.
Similar, obviously pricing, but you have longer duration of therapy, probably closer to, sorry, 12 to 24 months.
I think most investors are not quite at $2 billion for relapsed refractory AML. What are they missing? Where do you feel like your estimates disagree with what you hear from investors?
I think there are two parts. I think the total addressable market is often underestimated based on the fact that patients are hard to find. These are smaller indications. It's a little episodic, and you're also treating patients. You need to treat patients as early as possible. As I mentioned early on when we were sitting here, the 2,000 patients are only addressable if you get them second, third line. If you get the third, fourth line, fifth line, where most often they're being treated before Revuforj came to market, you're less likely to find 2,000 patients. You're probably a lot fewer than that, and the same goes for NPM1. I think they're missing, they're definitely missing that.
They're missing the fact that the patient population is likely larger or at least more accessible with a drug like Revuforj than previously. Then I think it's time on therapy, right? It's the ability to get patients, certainly for KMT2A, we've changed the paradigm. We've been able to treat patients, get them to transplant. About a third of our patients are now being transplanted in our clinical trials. When we were treating them later lines, it was about 25%. Keep in mind, before Revuforj came to market, patients who were about third-line patients were treated for transplant about 5% of the time. Now we've gone from 5% to 25% to a third. We think that number could grow to probably half or more, which would be an amazing thing for these patients.
That leads to more ability to put them on maintenance, which we think could go 70%-80% of patients going to maintenance post-transplant. Again, unprecedented numbers and things that we're proving out, but before Revuforj was on the market was not possible. I think those are some of the things that they're missing. Can you remind us of Syndax's strategy to access the European market? How important is the European market in relapsed refractory leukemia? Look, it's important to get the drug to as many patients as possible, and that's on our minds constantly. I think we're set up for success. Our trials have been well done in the US. Obviously, we have approvals here.
The question for us is, do we seek approval ex U.S., on, in relapsed refractory, or do we do it, based on our global trials in the front line? We are evaluating our regulatory options for bringing the drug to market outside the U.S. in any number of these populations. I think we have, you know, an evolving but important strategy to do that in the near, in the relatively near term. Moving to the combination studies in front line, can you discuss your overall strategy for getting Revuforj into the first line? Yes. Very exciting. We're excited in the sense that we have a drug that's approved and is now standard of care in relapsed refractory and certainly best-in-class profile.
We have the most data in terms of combinations. As you may know, AML is treated in combination. There are two sets of patients I mentioned. The unfit patients, the ones that are not fit for intensive chemotherapy, and the ones that are eligible for chemotherapy, and they take high dose intensive care intensive chemotherapy. We are testing our drug in combination with both with both regimens. We've started pivotal trials based on the results that we've seen in phase two trials in combination with both of those sets of agents. Right now we're enrolling patients, opening sites. We haven't guided to enrollment. We haven't given an update there. We feel like we're ahead and pacing very well to be first to front line.
These are, you know, well-designed, powered trials, with accelerated endpoints that can bring the product to patients even earlier than full readout, which is fantastic. When we think about the unfit population, in combination with Ven-Aza, about 450 patients, dual primary endpoint for one, for accelerated approval is CR, and the other is OS. We are looking at these endpoints in our phase 2 trial, but we're certainly building our pivotal trial to enroll and get the drug approved as quickly as possible. Of course, in the unfit and the fit population, in combination with IC, this is also an NPM1 driven trial. We're enrolling patients in combination there. Two endpoints, MRD-negative CR and EFS.
They're dual primary, so you can win on either. EFS, MRD-negative CR is the accelerated endpoint. We think through efficient design, best profile, the ability to move as quickly as possible, we think we'll have robust data in the front line setting in the next handful of years. In the interim, we're building data sets that support use in combination, and very purposeful, I'd say, in putting out data over the last few years, certainly this year at ASH, where we had multiple combination trials that read out and also real world data to support the use of the drug and combination for future. What is your guidance for when we could see the first-line pivotal data? What year would that likely be in? Well, we haven't guided on that.
Thank you for asking. I think we feel very comfortable about the fact that we'll be first to front line. We started first. We're efficiently designed. You know, over the next, I call it, handful of years, we'll be there. We'll be there ahead of competition with what we already know to be, you know, best profile based on data that we've already seen. We feel like these are, you know, sufficiently de-risked trials to get us the results that we need to stay exactly where we want to be, which is ahead of everybody else. One of your competitors has gotten to data in 2028.
Is your guidance to be first to data mean that it's gonna be before 2028, or are you thinking that those timelines are gonna slip? I know, Keith. What do you think?
I stand by Michael's statement that we expect to be first. Notwithstanding guidance given by others.
Okay. Well, I tried. All right. For this year, you've got it to a steady stream of data from first-line trials, maintenance experience, and real world experience. Can you be a little bit more specific, what data are we going to get, and at what meetings? Yeah. Lots of data coming. I'd say we'll be represented well at the major medical meetings. A few interesting pieces of information. Beat AML, one of our cooperative group trials, as well as our SAVE trial, which we're doing with MD Anderson, both of those will have updates later in the year at medical meetings. Again, these are looking at the newly diagnosed patients in combination. SAVE is in combination with Ven-Aza. Beat AML is in combination with Ven-Aza as well. Oral Aza with SAVE.
Those are two different regimens, very important updates. We'll be looking hopefully at OS at a later time point than we've seen it before. More mature OS, which I think would give us even more confidence now than we've had, which is looking at these trials that are enrolling in the front line. Our front line trial is going. We have this data which will continue to emerge and support that. People tend to look at VIALE-A as the trial of where Venetoclax was approved. Looking at that relative to OS is going to be important in the later part of this year.
Of course, we have real world data that continues to mature for both maintenance as well as combinations with venetoclax as well as other targeted therapies. That will be, you know, specifically out later this year. Intensive chemotherapy. Our phase 1 trials will be updated, looking at. There's two of them. There's one is a company sponsored, and one is MyeloMatch, which slightly different regimens of intensive chemotherapy and how the drug could be utilized there. Real world evidence around maintenance, very important piece of how the drug gets used with maintenance. We had a trial at Moffitt that'll get updated. There'll be more work with maintenance coming out from MD Anderson later this year. Important on maintenance.
It's a big piece of the business, how we grow the business. Physicians wanna understand, okay, what's the proper dose? How long do you treat them for? These are important questions. I think they have resolve to do it, and we've seen it in the business as it continues to grow. This is, these are the types of questions more data can help answer, and we are committed to, supplying that. Lots of data coming, lots of, exciting things to look forward to.
On the competitive environment, we're aware of at least four other meninins, in development, or in case of one other commercialized. How would you assess the competitive landscape?
I think we've been consistent here. you know, we feel very confident we have the best profile among the other menin inhibitors. we are far ahead in terms of data accumulation. We have approved product with indications now. We've been on the market for more than a year. Being first, having first mover advantage, critically important. Having best profile, extremely important. An organization that is set up for success, having, you know, the right level of medical support, all drive utilization. The fact that we have, you know, formulary coverage of almost 100% within a handful of months, so the drug is fully covered by all plans, that is a huge advantage. All of these things add up to a strategic advantage.
From a profile perspective, I'll go back to the fact that we have the broadest set of indications, so adults, pediatrics, AML, ALL, KMT2A, and then also for NPM1. We have all of it covered, and, you know, from a efficacy standpoint, this is an efficacy-driven market. Physicians think first about efficacy. What will get my patient to potential remission and maybe even a, and a cure in some cases with transplantation? Our drug does that better than any of the other drugs. I think they think first about efficacy and then of course, safety and tolerability. The drug's well-tolerated, characterized. We've treated, between clinical trials and commercial use, over 1,500 patients. Nobody can match that.
Having that kind of experience, having worked with physicians now for months, for them to get comfortable and deliver the drug where they need it, when they need it, all of that is just very, very important to building your competitive advantage, and we've done that. We feel like everybody else is a little bit late to the game and, you know, at best undifferentiated.
Turning to Niktimvo, can you give us an update on the launch and in particular remind us of the metrics that you gave on the recent earnings call?
Sure. Niktimvo in chronic GVHD, third line plus indication, the drug, the revenue grew at about 22%. We treated about 1,400 TRx or patients from launch. And, you know, we're growing the brand both from a new patient start, but also from a persistency standpoint. 60%-70% of the patients from launch are still on drug. This was as of about 10 months, 10, 11 months. That's quite a good number. This is a population that this is chronic treatment, the longer you can keep them on in remission, the better off they are, of course, and this drug seems to do this better than its competitors.
New mechanism of action, so it has the opportunity to potentially combine with other agents, and we're looking at this in combination. This has long, long-term viability relative to just being a third line plus agent. We're starting to penetrate. We talked about penetration on the call. About 20% of the patients, new patients are third line now. Then we have a high percentage, maybe even dominant share of fourth line. That will eventually move up. We should be in combination. We have trials reading out to substantiate this combination with steroids, also with Jakafi, which over the next few years will substantiate that position. The drug is starting to be used earlier and earlier, and patients staying on for months kind of have led to a banner year, a first year.
It's not even a first full year of sales. It was 11 months, $152 million in sales, which is significantly more than the $137 million that Rezurock did in its first full year of sales. We feel like we're on a different trajectory, and that's unusual for a product that comes after the product before, which is an oral drug, Sanofi's oral drug, Rezurock. We feel like we're in a very good position to grow this brand. Continue to expand. You know, very good quarter for Niktimvo.
How would you size Niktimvo's market, first in the refractory population, but then should it move forward into the first line? How much larger would it be?
Right. The relapsed refractory setting, third line plus is about 6,500 patients. When you get to the front line, it's somewhere between 15,000-17,000 patients. Again, this is all chronic GVHD. The drug is priced somewhere between $25,000-$30,000 a month. We expect patients to be on for months. This, you know, whether it's, you know. We know data for 12 months plus is very significant, but we think this is not gonna be a year, it could be several years for patients, and we've seen patients on drug for three, four years through our clinical trial. Could be a very large market opportunity. I know we feel like relapsed refractory is $2 billion plus.
Again, frontline, if you add up all of those patients at 15,000, 15,000-17,000, should be more than $5 billion.
Syndax is collaborating with Incyte on developing Niktimvo and other fibrotic indications. Investor interest is growing in IPF. We're gonna get data later this year. Can you remind those who are less familiar of the design of the phase II and the endpoints in particular?
Sure. The phase II, this is idiopathic pulmonary fibrosis area very high unmet need at 150,000 patients in the U.S. You know, need of new medicines. They need new mechanisms. They need new medicines that can really impact their disease. The trial is set up as a phase II proof of concept study, 135 patients randomized two 2 to one on top of standard of care. The endpoint is FVC at 26 weeks, which is a critical time point for, as we know, for these idiopathic pulmonary fibrosis trials, where the curves tend to separate at 26 weeks, and you can model out to 52 weeks, which is the endpoint of the pivotal trials.
It's both sized and powered, significantly powered to detect, we said at least a 40 ml difference in rate of decline relative to FVC baseline. That would be not only statistically significant, but, you know, highly clinically relevant for this population. This trial is fully enrolled. I'll note, we noted this on the call, fully enrolled, should be read out in the fourth quarter of 2026.
What gives Syndax confidence that this mechanism could work in IPF? What's the science to support it?
It's a very interesting set of discoveries around this mechanism. The drug is a CSF1R inhibitor, and the CSF1, by inhibiting CSF1, you have a profound impact on the disease-causing macrophages. The monocyte-derived macrophages, by depleting them, you have the ability to impact both fibrosis and inflammation, which are the hallmarks of chronic GVHD. They're also implicated, these disease-causing macrophages are implicated in IPF. There's a commonality here. When we looked at our GVHD data from our pivotal trial, a good portion of these patients, about half of these patients, had something called bronchiolitis obliterans syndrome. Bronchiolitis obliterans syndrome is a subset of GVHD, but it affects the lungs.
We saw about half of those patients get a response, a, you know, a very deep and durable response around their lungs. That is an unusual result. When you think about the commonality in disease from bronchiolitis obliterans syndrome to IPF, you see that there are not only mechanistic commonalities, but the ability to... You see that there's this fibrotic and inflammatory condition in IPF that is quite similar to bronchiolitis obliterans syndrome. I think that led to quite a lot of interest in putting a trial together that could test this. We did that with a, you know, a robust test in phase II at a dose we feel we've explored pretty significantly in GVHD, so we're going at the 0.3 mg/kg dose every two weeks. It's an IV drug, we'll administer this.
You know, we feel like this is a, you know, well-tolerated, very efficacious dose. It was the most efficacious dose and best tolerated dose in our GVHD trial. That, you know, for us, gives us all of the underpinnings. I'll also add, pre-clinically, we have a lot of information pre-clinically about this drug in IPF. This was first conceived before we went to GVHD. This was conceived as a drug for IPF. That was all the pre-clinical work was done in IPF, supports this. We haven't published a lot of that work. Maybe one day we will. But we think that both pre-clinically and clinically, we have the support that we need to have a successful trial.
We'll read out at the end of the year. It's exciting.
Maybe to finish on the balance sheet, Keith, can you remind us the current cash balance, your guidance for expenses in 2026, and how long you think that cash balance will support operations?
Sure. I'll begin by saying that, guidance is we've been pretty clear that we have enough cash to get to profitability. You know, we're very fortunate to not only execute on one, but 2 extremely successful launches, last year, which is very unusual for a biotech our size. Ended the year with about $400 million in cash on the balance sheet. We've committed to keeping operating expenses flat. Today the guidance is $400 million for R&D and SG&A, not including the impact of non-cash stock comp for this year and the foreseeable future. On the road to profitability for sure.
Yeah.
Perfect. With that, we're out of time. Thanks so much, guys.
Thanks.
Thank you.
Thank you.