Good morning, everyone. Thanks for, welcome to Jefferies Healthcare Conference in London. My name is Clara Dunn. I'm one of the healthcare analysts at Jefferies. Thanks for joining this session with Syndax Pharmaceuticals. I'm joined by Chief Executive Officer Michael Metzger and Chief Commercial Officer Steve Kloster. Welcome.
Thanks, Clara. Great to be here. Appreciate all your work and covering us, and good to see everybody.
Thank you. It has been a really busy year for Syndax, I have to say, with your two commercial products launching and label expansion for Revuforj, and heading into ASH. You have a lot of important data readouts as well. Really a lot to talk about here. You know, maybe just to set the stage, Michael, could you give us maybe a high-level overview of the company's story first?
Sure. Be happy to. As you said, it's been an exciting and important year for Syndax as we've expanded our ability to build our business. We have two approved products in the last 15 months. We've gotten three approvals, spanning hematology within oncology. That's the focus of the company. Two molecules, Revuforj, which is for acute AML and ALL, two subsets. One, KMT2A, which was our first approval last year. And more recently, in the last few weeks, NPM1, which together makes up about 40-50% of the patients within AML and ALL. A very targetable but large set of patients within the relapsed refractory setting that extends to the front line. We'll talk about that today as well. Right now we're focused on launching the product and have done so for about a year in KMT2A, really in the relapsed refractory setting.
That's exciting. We also have another product called Niktimvo, which is for chronic GVHD, approved in the third-line setting, third-line plus. We are launching that product well, and it's done fantastic, as Revuforj has as well in this first year of launch. It's the same field force, same targetable audience. It fits in very nicely with what we're doing in the U.S. as a commercial opportunity where, again, we see, you know, a $2 billion opportunity in relapse refractory extending to front line as we continue to develop the program in combination with standard of care agents. We're off to a great start with both of these products and really resetting benchmarks for the industry in terms of what you can do in targeting patients, specific patients for AML and ALL and also for GVHD. Setting up well for our ASH.
We always look forward to ASH. It's a big event for us as this year we have 23 separate abstracts, 12 for Revuforj and 11 for Niktimvo, six oral presentations spanning the gamut of monotherapy, combinations, also looking at real-world evidence, the first real-world studies being done with Revuforj in maintenance, also looking at combinations. There's a lot to talk about on the Revuforj side and, of course, on Niktimvo as well, where we look at the extension, the real duration of therapy that's playing out in the real world, as well as follow-up to some of our pivotal studies to see how long patients are staying on. It's really helping us to build what will be the future of our business, extending patients in terms of durability and extending their utilization across these different pieces of the business.
As you said, there's definitely a lot to talk about. Maybe just looking at the big picture, I mean, it's very impressive that launching two commercial products at the same time in parallel. Maybe tell us, what does success look like for each product in 2026 for you? What are the, maybe the internal metrics you're kind of looking at and holding yourself accountable for the next four quarters?
Sure. If we're, I'll start with Revuforj, which, as I mentioned, is for patients who have KMT2A, acute leukemia, and now NPM1 in the relapse refractory setting. For KMT2A, these are, I would describe them as a younger patient population, average, 30 to 40 years of age. We are now treating them in earlier than we did in clinical trials, so second or third line, so first relapse. There's really no standard of care that is effective for these patients. Physicians are driven to put them on therapy as early as possible, drive them to a full remission, get them to a transplant, which could potentially be lifesaving for them. Ultimately, once they've been graft from their transplant, put them back on therapy and maintain them in a maintenance setting.
What we're seeing in the first quarters of launch, we're seeing patients do just that. They're being treated earlier. About 70% of the patients are second or third line. We're seeing about a third of our patients go to transplant, and about 35-40% of those patients come back on post-transplant. Those numbers, we're tracking these very carefully. Those numbers should meaningfully go up in terms of number of patients transplanted, number of patients coming back on therapy, which drives, of course, the franchise forward in terms of revenue. These are sort of unprecedented numbers for this population. We're making a huge impact for patients. As we think about growth drivers, we're thinking about new patient starts. Those continue to penetrate a population of about 2,000 patients for KMT2A in the relapse refractory setting.
We continue to build through that. We'll be about 50% penetrated on this incidence population in 2025. Twenty twenty-six will extend that. We'll also have another important driver. The patients coming back from maintenance, they could be on extended therapy with Revuforj for many months. That we think will meaningfully build as a revenue driver in the fourth quarter of this year and then, of course, into 2026. That business should meaningfully build. The next driver of the business beyond what we're doing with KMT2A's NPM1. That launch is off to a fantastic start. It's a running start, as Steve likes to say. A lot of momentum. We've already seen some off-label use from that product, as we were launching in KMT2A.
Not a surprise because physicians know how to use this drug, and they have a big impact for NPM1 patients as well. We'll extend that. It really should be a good push into the fourth quarter, build that business into next year. We feel like we'll be a dominant player in, with our, first-in-class and best-in-class agent in both KMT2A and NPM1. That's how that business builds, you know, formably. I would say, for Niktimvo, we're building this, you know, agent in the third and fourth line. We've sort of dominated already the fourth line. Now we're moving into third line, extending the utilization there. I think the drug works very quickly. Patients seem to stay on it for many months, which is really quite encouraging. That will build over time. We've seen 80-90% persistency of patients since launch.
That means patients are staying on for many months. That will continue. That business is building, every day. We have had great performance there. We think that will build, you know, consistently and robustly into next year as well.
Great. Maybe let's first focus on Revuforj. I mean, it's still early days after the label expansion. As you said, you know, after the NCCN guideline inclusion, you've seen off-label use. Maybe just could you talk about, you know, after the label extension, what kind of uptake you've seen so far and what kind of feedback you've received from physicians as well?
Sure. Maybe I'll let Steve address that.
Yeah. As Michael said, it's a running start into NPM1. It's early days. I mean, there's a natural driver with NCCN guidelines, which we had late September. The approval, we didn't see any, you know, meaningful impact. We'll say at the end of the quarter it came too late. We're seeing early pickup, which is great. We had a very good October. I think Michael talked about the drivers for next year. Importantly, the same account base that's been prescribing for KMT2A, having very positive experiences with Revuforj. It's the same physicians and same accounts, which will treat NPM1 patients. Importantly, for the launch of the drug, the business wasn't really concentrated in the largest institutions. We'll call medium-sized academic centers, smaller academic centers, community oncology has all participated. We thought about the space and competition years ago.
It's not something we've just thought about now. Getting ahead of the game, exceeding expectations both in how the product's performing, but how we service accounts is also incredibly important. Things like formulary access, which drove at the launch, has been a real differentiator. Getting patients on drug within just a handful of days has also been important. That will continue as we move through this, you know, back half of the year. Mike, Michael, talked about the drivers, and we'll see that in this quarter and meaningfully impact sales and obviously set us up for a fantastic 2026.
I also want to quickly touch on the update on the label following the label expansion in NPM1 population. What kind of feedback have you received from the physicians regarding the QTC warning addition on the label? Especially for those who are already prescribing Revuforj with KMT2A patients, have you seen any change on the prescribing behaviors?
Yeah. Great, great question. I think we were thrilled to get approval in NPM1. We were first to get the approval there. The label is, we think, quite supportive of everything that we need in order to promote successfully in this indication. As Steve said, we've had a lot of experience with KMT2A. These are the same physicians who are treating NPM1 patients, and they've already used the drug successfully for the past year. I think that experience kind of just sets us up for success. The label, when you related to, I think you mentioned QT, we have a monitoring requirement for QT. Importantly, I think probably 50% of the drugs in the category have a QT, some QT liability. Monitoring is very, very routine for physicians. They give EKGs to patients when they walk in the door.
They monitor them for the first month or so. That is in our label. That has been our requirement from the beginning. With the new label, that has not changed. They do the exact same thing that they've done from day one. We talk to physicians upon approval. Nothing has changed regarding what they will do. Their decisions to treat patients are firmly guided by efficacy. This is an efficacy-driven market. Our product is the most efficacious in the category, very well tolerated. Safety is now well studied and quite strong. We feel, and they feel, that this is really, you know, business as usual and an exciting way to enter into this market. We are hearing very good things. We've talked to probably about a thousand physicians as we've launched this product in the second indication to just, of course, start the promotion.
It has been exceptionally well received at this point.
Also maybe quickly touch on the advocacy you mentioned. Obviously you do have, you know, in my view, a pretty differentiated overall response rate as well. Maybe just tell us a little bit of the significance of that to physicians.
Sure. Overall response rate, for our drug is, close to 50%. That means about half of the patients are actually clearing their tumor. When I said before, this is an efficacy-driven market, these are very sick patients. They've exhausted other therapies that they've taken, and they haven't, at this stage, they're in need of new treatment. They haven't done particularly well. Now we're at a stage where they can, half of these patients can clear their tumor. We're talking about within a month or two, which is an amazing result for these patients. Hopefully you can drive them to a transplant. Not all patients will get transplanted, but a lot of patients will stay on drug in remission for an extended period of time. That is a fantastic outcome for these patients. That's what the physicians think about.
Overall response rate is key. I think duration of response is important. We've seen, you know, a very good extended 23 months in the responder population for the patients that were on this pivotal trial for NPM1. They have a very, potentially a very good outcome, and the drug is very well tolerated. I think these are the opportunities. I'll just remind you that it's a very broad label. When physicians think about their patients in this category, they think about KMT2A, AML, ALL. They also think about NPM1, adults, and now we have pediatrics in the label. With the ability to dose patients with different dosage forms, we have a 25 milligram, a 110, and a 160. There are different strengths that you can give any patient.
I think that's really important as they think about how to dial in the specific dose for these patients. That relates to efficacy. It relates to safety and managing any toxicity that may occur with any product, especially, you know, I would say, as related to Revuforj. I think we have the flexibility of dosing, the efficacy profile, the range of indications to really deliver for patients and for physicians as well.
You recently said, around one third of commercial KMT2A patients receive a transplant, and around 35-40% of them get back to therapy after the transplant. How do you see this dynamic evolving over time? What about NPM1 patients?
It's very important. I've already mentioned it, that this is a great outcome for the KMT2A population to receive, to get into remission quickly, a month or two to get into remission, quickly get to transplant as many patients as possible. You're right. A third of patients today, that's improved from where we saw a clinical trial, which in the clinical trial, about a quarter of patients in third or fourth line were receiving a transplant. If you think about that related to before Revuforj, it was about 5% of patients getting transplanted in the third or fourth line. That's a huge difference. Now we're at about a third. That's even better than what we've seen in clinical experience. It's because in part we're moving up line. We're seeing patients in the second and third line. We believe that will continue.
Moving from a third of patients, maybe to as much as 50% of patients in second and third line as getting a transplant, that would be an enormous change and positive one for patients. What comes on the back end of that is patients go to transplant and then they have an engraftment period. There is a short holiday where they're off of Revuforj, and then they reinitiate in the maintenance setting. We have seen patients, about 35-40% of the transplanted population, come back already for maintenance. We think that will meaningfully go up over time, maybe as much as 70-80%. We speak to physicians. It's universal. They want to use this drug for maintenance. That's a fantastic thing. It's going to take some time to build up to that level of 70-80%.
We think that could build the business meaningfully for KMT2A. The dynamic for NPM1, slightly different. It's a slightly older patient population. Physicians are becoming more ambitious about transplanting these patients as well. They are doing it. We've seen it in our trial. They're going to transplant in slightly lower numbers, but we think that will build up over time and get to patients coming back on for maintenance, which of course we're seeing in our, we saw in our clinical trial. We expect it in the commercial setting as well. The dynamic is not altogether different. It's just slightly different numbers, we think, for KMT2A versus NPM1 on both of those things.
As you mentioned, a drug holiday, how long is this drug holiday typically for patients?
Generally three to four months. It's a short period of time, and it varies by patient. It's not overly formulaic. They're waiting for their counts to recover.
What's the current treatment duration in real-world practice for, for Revuforj? How do you think it might evolve over time?
Right. The impact of maintenance will have a big, will be a big driver of how long patients ultimately stay on therapy. Because as I mentioned, there's this period of time where they come back. That will improve over time. This year we're saying it's probably four to six months on average for a patient to be on therapy. Next year that could meaningfully change, going from four to six to six to twelve months as we gain the impact of maintenance, patient coming back.
Great. Maybe if we could focus now a bit on the opportunity for Revuforj in frontline setting as well. For those who might not be familiar, can you also talk, discuss the ongoing studies for Revuforj in the frontline setting and then kind of your rationale for the trial design as well?
Right. Two very important regimens in the frontline setting. These are newly diagnosed patients who, if they're unfit, meaning they're unfit for chemotherapy, generally a slightly older patient population, they receive something called Venaza, Venetoclax and Azacitidine combination. Our trial, which we've started, we were the first to start this trial, pivotal trial in combination with Revuforj in this patient population called, we call this trial the Evolve trial. That is being done with a group in Europe called HOVON, the premier group for these types of trials in this patient population. We are up and running. We're initiating sites. The trial design is very well understood. It's a randomized trial in about 450 patients where we compare Venaza versus Venaza plus Revuforj. The endpoint for these trials, a dual primary endpoint with an accelerated approval endpoint as part of that.
That's, CR, complete response is measured. That could meaningfully change the timeline to get the drug approved, on an accelerated basis in the U.S. You add overall survival as the other primary endpoint. You can, again, you can win on either. That would be the ultimate, you know, full approval endpoint. That trial, as I said, is very important. We think that will become the standard of care in the frontline. I think you'll see some data at ASH, which is very important this year. If you're planning to be at ASH, I would, I would focus your attention on this trial. It's at the plenary session where they look at venetoclax/azacitidine versus 7+3. It's important to physicians that have, we've heard this over time, this drive to get patients to the right regimen and do it with less chemotherapy.
I think early signs seem to indicate that Venaza is favorable relative to 7+3, which could impact the overall use of the drug, our drug, even in the frontline setting. We think we're very well set up. We've generated the most data with Venaza and our, so far our combination, very well tolerated and highly efficacious, so that we're looking forward to that. We're also looking forward to getting that trial enrolled and being first to the frontline. The other trial which we're running, and we have data at ASH this year, 7+3. We have our phase one data, which looks at the dose safety and efficacy in two different populations, actually the same population, but two different trials, one being run by the NCI, one being run by us.
We'll have somewhere in the 30-40 patient range looking at early data in that population. We'll take that dose and we'll start our pivotal trial. We call that the Reveal trial. That'll be started before the end of this year. In summary, what you'll see from us in terms of execution, we'll have both of these trials up and running by the end of this year. We already have the Reveal trial up and running. We'll be first to frontline. We feel very good about that. We'll have supporting data at ASH around the 7+3 combination, which really will inform on dose. That's the setup.
There's also other data, in combination with one of the other ven combos that we'll have in newly diagnosed patients that will, I think, be very informative for physicians as they start to think about those combinations in those frontline patients.
Heading into ASH for your 7+3 combo in newly diagnosed and Evolve patients, what can be the relevant benchmark or, in terms of efficacy, we can look, we can think about?
For the 7+3 combo?
Yeah.
Right. I think the response rates are typically pretty high to 7+3 in the, you know, 70% range, maybe even slightly higher than that. Right now our data looks close to 100% in KMT2A, across both of those trials in the abstract. We'll see the updated data at ASH, but very, very high response rates. MRD rates, which is what they measure, measure of minimal residual disease, that's usually in the 30-40% range for patients. That is really thinking about the durability and how deep these responses are. We think we can be meaningfully different on both of those measures. Right now we're looking at close to 100% MRD in the responders as well.
You know, from a response rate perspective, I think it's something that we're looking forward to, but MRD is, we think, a low bar.
Great. For the last few minutes, I also want to talk about Niktimvo. Maybe for those who might be less familiar, can you talk about your partnership with Incyte on Niktimvo and then, you know, what is the path for opportunity in earlier line setting as well?
Right. Niktimvo's got off to a fantastic start. As I said, we're launching, and we're in the third line plus setting, making a big impact, growing into third line. We're really already dominating fourth line. The opportunity there is $2 billion in that setting. As you move into frontline or earlier settings in combination, we're looking at two different trials that we're running right now with our partner Incyte. We have a steroid combination, which is frontline, and a combination with Jakafi, which is a phase 2 trial, which is delivered in the second line. Together, that could be a very formidable set of data coming in 2026-2027, that timeframe. We think that that extends the market opportunity to probably more like $5 billion.
I think the opportunity is really to keep patients on drug in remission for long periods of time, which we seem to be delivering on very well with Niktimvo. That again will help us, you know, really build this market, expand the market, if you will, for that product.
You also have over 10 presentations at ASH for Niktimvo.
We do.
What are, you know, what are the key presentations we should look forward to?
I think there's some follow-up from our Agave trial, which we find very interesting. Again, there are two things that I would point your attention to. One is a subset of patients who have stayed on therapy, continued on therapy for an average of close to three years. That supports the long duration that we're seeing and that we expect to see. We think that's even a low, a low mark of what could be possible in the commercial setting. Patients are in dire need of therapy, and so they're looking for something that keeps them in response for an extended period of time. That is what this is delivering on. That piece of data I think is very supportive of what we're seeing, what we expect to see.
We're also following up on patients where they were switched in the real world setting. You could see patients that switch from two weeks, a dose every two weeks, to a convenience dose of every four weeks. We have some trial data that looks at that. The average patient is on for close to two years and well tolerated regimen. It's very easy to do. I think that wasn't one part of our label. We didn't get a four-week dose. We have a two-week dose, but you can dose it, you can double that dose. It seems to be well tolerated and effective and over an extended period of time. That's important data as well. There's some trial and progress work that looks at, you know, our combination with Jakafi as well, that seems to be very well tolerated.
Again, that data is not fully available yet, but that's trial in progress. A lot going on with Niktimvo as well.
You are also taking Niktimvo into IPF with a randomized phase two trial. Maybe talk about the timeline which you expect data and, what, you know, what kind of, what gives you confidence for Niktimvo's potential in IPF as well?
Niktimvo's, as you mentioned, we're doing a phase 2 randomized trial on 135 patients, two to one on top of standard of care. That trial is enrolling very well in IPF, new mechanism of action in IPF. The rationale here is that this drug has a pretty important impact as a CSF1R inhibitor on the macrophage, which sort of sits at the nexus between inflammation and fibrosis. The ability to control both with one mechanism would be a new offering for these patients within IPF. We're doing this rather significant trial on 135 patients. As I said, it's randomized, looking at FVC as the primary endpoint. The ability to impact this disease, I think, will be pretty telling. We have the trial enrolled by the end of the year. We'll have data in the second half of next year.
Very large indication, approaching 200,000 patients in the US, dire need of new mechanism, new therapy. We hope to deliver on that as well. It could be a very important driver and milestone for the company and for that program. I think we're very excited about it and our partner's very excited about it as well.
Very looking forward to it. Maybe lastly, how are we thinking about the profitability guide?
Yeah. Look, we've said, we've made a strong set of statements around profitability. I think it's important for our story. We have two products that are contributing very significantly. The ramp of revenue is robust. We have guided to stable expenses over the next few years. We can do all of our priority studies, as we've talked about today, and drive what we think is important data for both programs within that stable expense base. We think we'll be profitable in the next few years, which, with discipline and robust sales, we can certainly get there. It will help us really drive the narrative going forward.
Great. We will wrap up our session here. Thanks, Michael. Thanks, Steve, for sharing your time with us. Thank you to the audience for joining this session.
Thank you very much.