Syndax Pharmaceuticals. My name is Michael Schmidt, Senior Biotech Analyst at Guggenheim, and I'm very pleased to welcome Mike Metzger, CEO, Anjali Ganguli, Chief Strategy Officer, and Steve Kloster. I'm sorry, Steve Kloster, Chief Operating Officer, Chief Commercial Officer, and Anjali, Chief.
Chief Strategy Officer.
Strategy Officer. Thank you. I know you guys always show up as a team, which I really appreciate. So yeah, why don't we jump right into Q&A, Mike, to discuss revumenib? Obviously, you have had the recent FDA approval for KMT2A refractory AML, and so you have now made the transition into a commercial company, actually with two on-market products, but on Revuforj, which was approved last November. Yeah, maybe start out by discussing perhaps how the initial launch has been going. Anything you can share on the early commercial experience so far?
Yeah, well, first of all, thank you for having us, Michael. Good to be here. Good to see everybody, and I'll turn it over to Steve to talk a little bit about the launch and how it's going so far, but I'll just make a couple of remarks. First, we have gotten off to a very good start. I think we feel great, and we'll have two products in the market now, not only Revuforj, but Niktimvo as well. We'll touch on that, so we have made that transition to a commercial stage organization, which is a big move for a company our size. We are well-resourced to do the work and really be successful in these important spaces of business, deliver drugs to patients, so we are feeling quite good about our position, and maybe I'll let Steve mention what specifically is going on.
Yeah, so a very encouraging start for Revuforj. The company was well-prepared for launch. I think great launches don't happen by accident. It's companies who are ready early, so we staffed up early, well in advance of the approval, both on the payer side and on the sales side, have an incredibly talented team that's executing in the field now. The drug, as we know, was approved in November. We had drug in channel. Within five days, we had our first patient paid through insurance the next day. Formulary access, of course, is going to build over time. I think we're going to do it quicker than most early days. There's a medical exception process getting drug paid for. The good thing is we've seen it through all the different payer channels, Medicare Part D, commercial, and Medicaid. That is great.
And in terms of where patients are coming from, and of course, we'll share more at upcoming earnings calls, but it's pretty broad. We're building a good foundation of business when you think of where patients are being treated, both in the academic setting and the community setting. We're seeing patients come in from both small, medium, and large-sized academic institutions. We're even seeing some come in from the community side, which is a little unusual. This tends to happen later, but I think it's because there's need. Patients are being identified through diagnostic testing. The drug is fairly straightforward and easy to use. The dosing is clear. We help them through that process. So early days, but we believe off to a really good start.
Yeah, can you maybe share a bit more about just the process of getting a patient onto therapy in terms of testing, gaining access, reimbursement, and then streamlining that process?
It's really important, and I think some companies do it well and some don't, and the reason you do it well is because you've got people internally that know how to do this. They've worked at other smaller companies, and you also pick the right trade partners, so I think most folks may know we have a limited distribution network. We've got a couple of great specialty pharmacies. We've got a hub, and it's all that. It's about that experience. It's engaging the clinician and getting the patient through, particularly in the early days. Insurance companies, this is a high-priced drug. There's no doubt they're going to put up some initial barriers, and you just got to push through it, and we've been able to do that successfully, getting patients on drug quickly.
In some cases, a couple of days. Others that take longer because insurance will continue to push back. You just push through those barriers. Payers want to cover, ultimately. I mean, they recognize the unmet need, the severity of the illness, and for any one payer, this is not a budget buster because the population is sizable from a commercial perspective, but not to any one payer. It's not going to crush their budget, so we partner with them, work with them, make sure patients are on drug, and then once they're on, it's how do we support them through that, make sure they stay on as long as needed.
Right, and then obviously, Revuforj is right now the only drug available for this patient population. And so yeah, how quickly do you think you can ramp and capture this opportunity in the U.S.? Maybe talk a bit about where patients are concentrated at academic centers versus the community. It sounds like you have some uptake there as well, but how should we think about the ramp to break into the capture the opportunity?
Yeah, it's a good question on ramp, and there's been other targeted therapies in the space. And I think when it comes down to KMT2A-r acute leukemia, relapse refractory, it's a terrible prognostic indicator. Physicians know that, so they're thrilled that they have something to treat. When you think of the label for Revuforj, it's as broad as can be, AML and ALL population from one on up. So the pediatric population is important. And I think when you think about the fall and the release of our own NPM1 data, followed by an approval, followed by ASH, and a lot of interest in the menin space, it's perfectly positioned Revuforj, right? So the awareness levels are incredibly high. Physicians do tests routinely. Every center does it differently, but we're there to help them find patients. How do they diagnose and identify them to hematologists who are treating them?
Off to a good start. And I think it'll happen. Of course, it's going to take some time. Range of patients at launch is first relapse to, frankly, patients that were on hospice. The early experience is important. The bigger that base of experience at launch, we often talk about first mover advantage. That's what that is. Doing a great job early, physicians gaining a lot of experience. If and when competitors come, there's less reason to look outside of Revuforj.
Right. And then I know you obviously can't promote to NPM1 at this point, but we've all seen the data presented, and I think it's well appreciated by physicians. And so anything you can share on, have you seen any unpromoted use at this point, and how big of a factor could that be in the near term?
Yeah, maybe I'll take that. I think the data is quite strong, and I think physicians have reacted well to it. And as Steve mentioned, we had the opportunity to be at ASH and really be in front of a lot of physicians. And so there's quite a bit of interest. I think our experience so far, obviously, we'll always promote on label. I think physicians wanting to use the drug and have seen data in NPM1 now. We'll get that data published and hopefully into guidelines soon. But they've seen that data, and they're reacting to it. They're also reacting to our combination data, which we've put out in newly diagnosed patients as well as the relapse refractory setting. So I think we've put out a lot of data, and there's some understanding now how best to use the drug.
We expect, and we have seen some non-labeled use. We are not in a position to talk about how much of that is yet, but I think we're experiencing some of that so far, and it's to be expected from the physician feedback we've received.
Right. And then I know you've in the past alluded to this $750 million U.S. market opportunity. I guess, what are assumptions here? Just remind us of that. And then the second follow-up question was in terms of maintenance therapy, has your experience reflected your expectation there?
Right. So the $750 million TAMS opportunity, speaking specifically about KMT2A, relapse refractory KMT2A, it's based on an assumption of about 2,000 patients in that setting, about nine months of treatment at a price point roughly $40,000 a month, which is what we have in the market now. So I think that nine months' duration of treatment really breaks down into about a third of the patients who won't respond to the drug but will have received some therapy. Two-thirds of the patients, based on our trial data, did respond and got to a clearance of their tumor. About half of those patients stayed on drug for a period of time. We estimate about eight months. The other half go to transplant and have the ability to go back on therapy. And a portion of those patients did go back on therapy. We've seen patients on for three years.
And so I think that averages out to maintenance for probably about 18 months. That's an estimate. We think it could be longer, depending on when we treat patients. We expect this to be a first relapse drug, a drug that is given right after patients relapse after one therapy. So the earlier you treat, the better patients do, the longer they stay on therapy, and that accrues to the benefit, obviously, of the franchise. So that is how you get to, if you do the math, on nine months, 40,000, 2,000 patients, it's roughly $750 million. I think there is upside to that number. That's based on an epi forecast, right, of 2,000 patients. There may be more patients than 2,000.
So we'll see how this plays out, but we do think it's a rather robust place of business, which, of course, we're the only drug to be approved there. We expect that we'll be the only drug approved there for quite some time. And we are making every effort to exploit that opportunity. I'll just say on the maintenance side, again, this is in our own experience today, it's early days of our launch, right? So we're only a couple of months in. I think maintenance takes a little time to build, so that likely won't be part of the equation until maybe later in the year when we start to see patients come back from transplant. So that's a work in progress.
Makes sense. Great. Well, then maybe switching over to discussing the NPM1 opportunity where you obviously had the top-line data disclosure last fall and then more detailed information presented at ASH, where you did a subsequent analysis that resulted in this 26% CR/CRh rate. So my first question is, as we think about the regulatory path for NPM1, is the anticipation that this ASH analysis is perhaps something that the FDA would apply as they review the data for the sNDA?
Right. So what you're referring to for the audience that maybe don't know the detail here, we had a primary analysis that was done on our NPM1 data that was statistically significant, 23.4% CR/CRh rate with duration of 4.7 months, which equates, we believe, to time on therapy of about eight months. And we had additional patients that were enrolled in the trial after our primary analysis was conducted. I think the follow-up data that we presented at ASH was in the additional 17 patients for efficacy had reached the evaluable stage, and that data yielded additional responses that pushed our numbers up to 26%. That was an ad hoc analysis. We will submit all of that data to the FDA. So they tend to do in single-arm trials.
We experienced it with the KMT2A population where they looked at a variety of our trials and pulled together a data set that they thought was representative of the population that they were approving. We expect they will likely do the same or something similar for the NPM1 population. They tend to like more data versus less data, and so we will provide that data to them. It is all, again, very consistent with what we had on the primary analysis. It is a higher point estimate. The duration was the same, so I think it's a more robust data set. Of course, we'll present it, and we think it's very highly supportive of approval.
Right. And then just remind us how you're tracking to this regulatory submission. There's obviously in the NPM1 space a little bit more of a competitive situation relative to the KMT2A, but just curious in terms of timing, how you're tracking that?
Right. So we said we'd submit the sNDA in the first half of this year, which we are on track for, and expect to get the drug approved, hopefully before the end of 2025. And that's the plan. We also, I mentioned earlier, we have data that we'll get into a publication and then hopefully into guidelines in the first half of this year. And so that will support use as we promote the drug on label for KMT2A, but for physicians who treat according to guidelines, that would be an opportunity for them to use the drug in that fashion.
Right. And then just for modeling purposes, what is a good assumption for duration of response in the NPM1 setting relative to the KMT2A patient population?
Yeah. Do you want to talk a little bit about that?
Yeah, sure. I can talk about that. So I think for modeling purposes, what's probably more relevant is the duration of therapy. So how long are they on treatment? And that would lead to, with EPI and price of therapy, that gives you your total addressable market. With NPM1, we have noticed that it takes a little bit longer for patients to get to that CR/CRh response, probably because they're older. And so the time to response was about three months, and then time in response was about five months. So we've been suggesting, based on the data in this trial, about an eight-month estimate of time on therapy.
Right. Great. And then maybe switching gears to first-line AML, which is obviously a much bigger commercial opportunity for this class of drugs. Maybe just to set the stage, remind us of where you stand in capturing the first-line opportunity with your development strategy.
Right. So the strategy is to first start with the highest unmet need population, which is the unfit front-line setting being in combination with Venclexta. So the trial to run right now, there's first-line Venclexta is approved for the unfit patients. We're going to be adding on to that doublet. So it's a randomized trial, which we are standing up now and expect to start enrolling patients in that trial. I think, again, that's the highest unmet need population. It's an OS endpoint. There may be opportunities to accelerate that. We are always in discussion with the agency about opportunities to do so, and we'll avail ourselves of that if and when that's a possibility. I think on the unfit side of the equation, we're conducting a phase one trial now. It's currently enrolling. We'll have some data in the third quarter.
That's again seven plus three plus rev to look at whether we'll add onto that doublet. And I think the measure of CR/CRh as well as MRD negativity, overall survival, all of those measures will be part of that assessment. I think the follow-on to that is looking at that segment of patients, patients who are fit, usually younger, and of course, have the ability to undergo chemotherapy treatment in addition to rev. That segment of patients kind of has some nuance to it, right? It's not just one population. And so our strategy is to both register in that population, but also generate data, guideline, do trials that potentially get into the guidelines more quickly. Some of these trials, if you're not careful, they could be quite large and take many years.
And so I think our approach is to not only generate a lot of data, but be in the right populations and get registered, but also get guideline access in order to facilitate use. And so that's a strategy we'll say more about as we go, but I think it complements very nicely what we're doing in the unfit population. As I said, we believe we're considerably ahead in those populations, and the data that we've generated to date specifically with Venclexta has been quite strong in newly diagnosed patients, overall response rate 100%, MRD rate 95%. So you can see how we have an opportunity to add on just from a CR point of view. I think this is, again, an overall survival trial, which we believe we'll be able to impact as well.
Right. Obviously, there was some news yesterday from your competitor who has said they're planning to pursue an accelerated approval strategy in both the unfit and the fit patient population. Obviously, your Venclexta combo study is already underway. But yeah, maybe talk about your experience in discussing perhaps some of these things with the FDA and any opportunities to potentially incorporate accelerated approval strategies.
Right. I think our competitor yesterday kind of talked about their opportunity and their, quote-unquote, "alignment" on some of these things. I think that's maybe stretching it a little. I think these are ongoing conversations. I think there's quite a bit of interest in MRD negative CR and perhaps EFS as an endpoint for accelerated approval in the fit population. Quite a high hurdle. The agency has guidelines and guidance that they put out in 2020 that specifically address what they're looking for. I think it's an ongoing conversation. They've been willing to consider that in other indications, but so far not in AML. So we continue to have conversations as well. We're part of the industry conversations on change to guidelines as well as what could be possible in an accelerated approval path for that population. I think in the unfit patient population, it's the same.
We're still having ongoing conversation about that. We have an ongoing trial, which if there's an opportunity for accelerated approval, we'll, of course, avail ourselves of that as well. So I think early days yet to say that there's alignment on some of these endpoints. I think there's more work to do.
Right. And then, yeah, just on the fit patient population, the 7+3 combination, just remind us where you stand with those activities and what additional data you need to generate before you can start the phase 3, essentially?
Right, so the 7+3, I had mentioned that we're generating additional data, and we know we've done a lot of dose ranging work. We've tested our compound in combination with chemotherapy and other regimens, so we have a pretty good feel for what we would need to achieve and what the dose would be in that population, so we're just generating additional data to support that, and we'll have that data in the second half of the year, so nothing much more than that, just additional data.
Right. And then obviously, besides Kura, there's also emerging competition from J&J, other companies in the combination space in particular. So how do you see revumenib being positioned longer term in this sort of increasingly competitive space in front-line AML?
Yeah. I mean, I think it's all going to be about the data that we generate. And I think the preliminary data that we discussed at ASH last year is very suggestive that revumenib continues to have a best-in-class profile, whether it's in combination or as monotherapy. We're seeing significantly better response rates and CR/CRh rates in combination with Venclexta than what Kura and J&J have put out. We think the synergy and the overall profile of revumenib supports the best-in-class. And we don't see why that wouldn't hold true with the updated data that Michael just suggested that'll be coming this year in combination with 7+3. We have a really thoughtful strategy that we'll share at the right time. We're managing the competitive set very carefully, but I think we're taking advantage of our leadership position and making sure that we continue to dominate the space.
Right. So how should investors think about additional data disclosures from the revumenib program over the rest of this year?
Right. So just say that, as always, we've been transparent with how we put out data, right? And so I think we've always been very clear when data is going to come and exactly how it's going to be discussed at what time. So I think that's our approach. I think the data, I had mentioned potentially having guidelines this year. That's an important milestone potentially for the company. But data, seven plus three in the second half, the combination with seven plus three and rev, phase one, we'll have updates, we think, likely for the BEAT AML trial, which is Venclexta plus rev in newly diagnosed patients. That was updated at ASH, likely to be updated in the second half of this year as well. There are also Ghayas Issa's trial, the SAVE trial, which is Ven and Inqovi plus rev in both relapse refractory and now newly diagnosed patients.
That's enrolling now. That was updated at ASH. That'll likely be updated again. And I think they're enrolling not only for SAVE, they're enrolling NPM1, KMT2A, NUP98 patients. So I think that covers a broad spectrum of patients as well in that combination. So that will be updated, more duration, more patients. So I think there's a robust set of combinations that handles multiple segments that we're looking at.
Right, and to what degree are you still exploring revumenib's potential outside AML or hematological cancers?
Right, so we had talked about a phase I trial that we had ongoing for colorectal cancer, and that is ongoing as well. We should have an update, hopefully in the second half of this year as well on that, but that's the only, I think the only non-hematological indication that we're pursuing at this point.
So no plans to move into diabetes or some of those areas?
No plans to move outside of oncology.
All right. Great.
But maybe one thing to emphasize, Michael, we're also doing a trial with Ghayas Issa and Eytan to look at other indications within AML, similar to how NPM1 was identified and even NUP98, looking at that HOX/MEIS signature. And so there could be an additional 20% of AML that could respond to menin inhibition, and we're looking to generate that data as well.
Okay. Great. And then, yeah, I had a couple more questions on Niktimvo. So obviously, which is your GVHD product partner with Incyte, the FDA recently signed off on the smaller vial sizes that were approved a few weeks ago. And so, yeah, any comments you could provide on the launch activities, perhaps in GVHD and how those have been tracking since the approval came through?
Yeah. Steve, you want to hit on that?
Yeah, absolutely. It's early days, the drug was in channel last week. It's selling to customers this week. This drug had some run-up, right, because the drug was approved in August. So awareness level's high. I think it's a market that is in desperate need of a new agent. We've seen some success with Rezurock, same indication as Niktimvo. That drug's annualizing and actually delivered almost $500 million in sales last year, growing at 50%. I think that's a good analog. The disease is characterized by high symptomatology and incredible impact on quality of life. Mortality rate is there, but patients live for quite some time suffering, and Niktimvo treats fibrosis and inflammation, which are really the hallmarks of the disease, so too early really to comment. I know interest level is high on the compound. Our partner Incyte is the player in the space. That's why we chose them.
They're handling all the promotional activities. We do have a co-promote, and we have great visibility into strategy and investment levels. We remain closely connected to them, making calls on physicians. And for us, it's a very efficient call point and really complements both brands really well. So more to come, but good expectations.
Great. Thanks. Well, with that, I think it's time to wrap up. So we'll look forward to early commercial data points for both Niktimvo and Revuforj this year and then additional data for revumenib AML as well. So thank you. Really appreciate the time.
Great, Michael. Thank you.
Thank you.