Okay, welcome, everyone. I hope everyone can hear me. I'm Yigal Nochomovitz. I'm one of the biotech analysts here at Citi down in Tribeca in Manhattan. It's my pleasure to have with me for the first day of our virtual oncology summit the leadership team from Syndax Pharmaceuticals, Michael Metzger, the CEO, and Neil Gallagher, President, Head of R&D. So thank you both so much for taking the time to chat for about an hour on your pipeline and on your burgeoning set of FDA approvals. I think there are two, as I last counted. So, Michael, maybe just to set the scene, you know, just give us a quick rundown of where you are, where the business is, you know, what are the key priorities for 2025 and beyond, perhaps. I mentioned the two approvals, so of course we're going to talk about those.
But let's just set the scene, and then we can dig into some more specifics on the launches for both products. Thanks.
Yeah, terrific. Thanks, Yigal. Good to see you, and thanks for having us today. You know, it's a very exciting time for the company. As you mentioned, our two approvals, two new medicines were approved, first in best-in-class medicines. We'll talk about those today. Last, well, one this year and one last year, Revuforj, which is for acute leukemia and genetically defined acute leukemia, and Niktimvo for chronic GVHD and potentially other indications. Both are new, brand new medicines with new mechanisms of action. We're pioneering both within their respective spaces of business, so very exciting to be doing that. We have a U.S.-based field force, and now we've launched both products. Off to a good start, and we'll talk, I think, more in depth about that today. Certainly that's a priority and a focus for us, being in the initial launch phase with two products.
And then, of course, expanding into additional trials, really doing life cycle and making sure we pick up other indications of importance, bringing both medicines to earlier line patients in combination with standard of care therapy. And those trials are ongoing now and will be for, you know, the next several years as we build out these two important franchises. And look, the business has grown quite a bit. We are now, I think, what you'd call a fully integrated company, doing both development work as well as commercializing two important medicines. We think these are very large opportunities, multibillion-dollar opportunities, and we, you know, as first mover in these indications and with these new medicines, we think we have a very unique advantage to take advantage of and really build formidable franchises. So that's the focus of the business.
Having the two approvals behind us is, of course, building and giving us great momentum as we go into 2025.
Okay, great. And I just want to remind those investors listening, if you have questions for the company, just email me, yigal.nochomovitz@citi.com, and I will do my best to catch those and relay over to the management team. So let's start with AML, obviously the approval and relapse refractory. You know, tell us a bit of, to the extent that you can, obviously, given, you know, the disclosure and that it's very early, how are things going? How is the early uptake? You know, what can you say about the receptivity to Revuforj in the market, both in the larger academic centers and obviously in the community setting, which is no doubt an important feature of the market as well? So just give us some context for how it's going. You know, granted that you can't talk specifics quite yet.
Right, so it is early days. We started the, well, we launched the product. The product was approved. Revuforj was approved November 14th. We are in the channel, able to distribute drug to patients within five days, which is sort of industry best, which we're proud of, so we had roughly five weeks of experience in 2024 and, of course, continues into 2025. We will report our earnings first stub quarter in the, you know, March timeframe, so we have early March, we'll have that initial experience for everybody, but it's, look, I think what we focus on here is really three important things. One, can you identify patients? And two, can you get them the drug quickly? And three, can you get it paid for? And I think we've, in the earliest of days, have shown that we can do all three and do all three quite well.
So we feel we're coming out of the gate well. It's a very solid launch. I think we will have more to say about it, but so far, physicians are excited about what they're able to do with the medicine. I think a lot of physicians, you know, were involved in our clinical trials. And so this is an area specifically around KMT2A, a very high unmet medical need. So patients are in need of new therapy, and this is specifically designed for them. And so we're hearing and we're seeing that physicians are eager to get their hands on the medicine and get patients on drug. And so that's, I think, a really important part of any new launch, that physician utilization and physician interest is there.
We also had the benefit of ASH, which, you know, where all the physicians were together and we were able to have not only the drug was approved at that point, but we had great dialogue around the data and emerging data in another indication, potential indication of importance, NPM1. Same physician audience, of course, and a different mutation that is very important to this category covers between the two, KMT2A and NPM1, roughly 40-50% of the market. So it's new data, pivotal data was quite positive and well received by the physicians at ASH. And we expect over the next, you know, I'd call it weeks, months to get that data published and also supportive of potential guideline inclusion, you know, this year as well.
And then, of course, we'll file that data with the FDA as an sNDA in the first half of this year and hope to get the product approved in the second indication before the end of 2025. So there's a groundswell of interest and data as well as seeing how the drug works in combination. A lot of that was presented, updated, and presented at ASH. So we feel like this is the perfect way to launch a product where there's a lot of information and interest as well as good follow-through by the commercial team and the medical team to support the product when speaking with physicians. So off to a great start.
Okay. So obviously, you know, in the bigger academic centers, presumably there's much known about KMT2A, but I'm curious in the community setting, you know, what's the, how is the messaging working in terms of providing, you know, an understanding of the unmet need for KMT2A and then, of course, for NPM1? Is it widely appreciated that menin inhibition is a favorable approach? You know, what kind of educational efforts are necessary in the broader setting, you know, beyond the heavy-hitting centers to drive home the message that Revuforj is a really important medicine?
Yeah, I think it, again, I think this is traditionally in AML and ALL, about 80% of prescriptions are written by the academics who or the physicians who reside within the academic centers. And so that's a lot of who's treating these patients, but certainly the community has an active role in it as well. And I think over time, certainly with an oral medication where there's really nothing for these patients and they can be selected to these physicians, whether they're in a community or academic centers know who these patients are, they are eager to get their hands on the medicine and prescribe it to patients. And so we've seen early days, but we've seen good community involvement as well, which is a great sign for the uptake of the medicine. So that's fantastic. We expect it to build over time.
And the, you know, in terms of the education that we do, we have field medical as well as our commercial team out and speaking with physicians. Obviously, there's, you know, additional work we can do, publishing data and getting in front of the proper information in front of these physicians. So I think it's just the groundswell of activity and a second approval as well in NPM1 that could really, you know, get physicians in the community even more enlisted in using the drug than they already have been. But it's, again, early days are looking promising in terms of what the community could add to this important, you know, franchise.
Obviously, you know, the timing was, I guess I could say fortuitous in that you got the NPM1 data, you know, very much right after the approval. Obviously, you're still going to file that. How much is that, you know, the knowledge of that NPM1, which we know is about a three times larger market, helping the receptivity, just generally speaking, as far as the initial commercial campaign?
I think it's quite important. I think physicians are excited that the drug seems to work in NPM1 as well as it does in KMT2A. So that broadens the patient population quite a bit. There was other data presented by other companies related to NPM1 at ASH this year, which I think was, you know, that whole groundswell of interest in the mechanism accrues to our benefit, right? Because we're the only approved medicine out there. NPM1, we don't promote yet. We have to get the drug approved in that indication first. So we're strictly on label. But we do know that physicians are prone to write off label in this indication in particular.
And I think we've heard anecdotally, of course, that they will be doing that relative to Revuforj and how they plan to use it both for NPM1 as monotherapy and also in combination with chemotherapy and venetoclax as well. So I think there's, you know, the more data that we can generate to support the use and potentially get the drug first into guidelines for NPM1, as I mentioned, and then, you know, essentially get it approved in the near term, all of that will be quite important to the overall franchise.
So, you know, a piece of this too is not only the treatment before the transplant, but the potential for treatment after the transplant on the maintenance. So, you know, when you showed us that number, I think it was $750 million in potential marketing and sales for this, just for this first indication in the KMT2A. You know, can you maybe talk a little bit about how you see, you know, that number working in terms of the mix of the pre and the post-transplant? You know, what sort of assumptions are baked into that?
Sure.
It's not guidance, but it's just sort of an illustration of the potential.
Right. It is an illustration. And I think we base the illustration on our data, right? And then what we've experienced in our trials and what we've illustrated or spoken about and continue to provide information relative to the projection of $750 million in the U.S. for relapse refractory KMT2A. It's based on roughly 2,000 patients in the U.S. and time on therapy, roughly nine months across various segments of patients. And when I say that, you know, two-thirds of patients based on our trial, two-thirds of patients get to an overall response, meaning they've cleared their tumor, and a third don't. So I think a third of the patients have shorter-term therapy. And the two-thirds of patients who get to a complete response, about half of those go on to transplant, and the other half stay on therapy for roughly around eight months or so.
The ones that go to transplant, our experience is they, you know, a large percentage of them have the opportunity to go back on what we would call maintenance therapy after engraftment. So there's a period of time where they're on therapy, they get to a response, they go to transplant, and then they come back on maintenance therapy. And that maintenance therapy we've seen patients on for, you know, out to three plus years now. So I think it varies depending on what the physician preference is to keep them on therapy for, you know, sometimes it's a year, sometimes it's longer. Some physicians say they won't take them off therapy until relapse. And so, you know, the hope is to keep these patients, specifically KMT2A, who are very young, get them to a transplant as quickly as possible and get them into remission and keep them in remission.
I think the maintenance really helps with that. The assumption on the 750 really assumes that across the patients who respond and some of even the patients who respond less well, it's probably not about nine months of therapy. Could be a lot longer than that, depending on when they access care, meaning if they're treated earlier. In our trial, they were treated sort of third, fourth line, but if they're treated as sort of first relapse, which we expect based on what physicians tell us, and that is, of course, on label, first relapse, we know patients who come on earlier generally do better and stay in remission longer.
And so I think that's the paradigm we expect that will unfold over, you know, the next, you know, few years, that patients will actually get treatment earlier and that maintenance will become more of a factor as they stay on and in remission for quite a long time. So, you know, based on what we know today, I think the market opportunity at about $750 million. And for NPM1, similar types of assumptions going at, you know, eight or nine months of therapy across that population. So that together, they're about $2 billion in TAM for both KMT2A and NPM1 relapse refractory disease.
Okay. And I think among the factors you mentioned early in the launch was obviously, you know, getting remunerated, getting paid, and having a reimbursement work out. I assume that's going to be, you know, if I can say fairly straightforward, given the molecular diagnosis and the dire medical need. Anything you want to say there in terms of maybe fine-tuning or things you've learned even in these first few weeks that just need to be, you know, checked or modified, or is it just going according to the plan?
Yeah, you know, we've had the benefit of hiring probably the best team we could have imagined in this space, extremely experienced, you know, team of people who, you know, work on payer relations to trade and have been in place at Syndax for some time and really have the experience of launching many, many products in this category. And so I think the experience of our team has really come in handy as we've launched this product. And so I don't think there are a lot of surprises. I think there have been, you know, opportunities to always fine-tune things, but I think we've executed quite well. And, you know, the proof of that is we're getting reimbursement across all payer categories, commercial and government.
You know, when we meet some resistance, which is with every new product, because we're not on formulary in 100% of, you know, places just yet, but we are building and made incredible progress early on with getting on formulary. But there is an exception process that you'll have to go through as the formulary access builds over time. But we're, you know, quite adept at working with the physicians and patients and their families to get the product, you know, paid for. So so far, it's worked out very well. We expect it to continue to build over time.
Okay. You mentioned obviously NPM1, the filing. Just can we just do a little box checking on that? Just what else needs to happen in order to get that filed? It'll be an sNDA, as I understand. Is it a reasonable expectation that the PDUFA would be in 2025, or can you comment on that? And just obviously everyone is, you know, very interested in seeing that launch following this KMT2A launch.
Yeah, I mean, Neil, you could probably comment on that. I mean, I think our timing is, as we said, and without any specificity, we'll submit the sNDA in the first half of this year. And then, you know, look to get the product approved based on, you know, the FDA's timeline before the end of the year. Again, we don't have, you know, we don't have a PDUFA date yet. So I can't say with certainty, but that is our plan and our expectation. And I think the amount of work that is going on at Syndax relative to the sNDA, I mean, the benefit, of course, is that we just submitted and got approval for the drug. So I think the agency is well aware of our data and what the drug is all about. And so this is not a first review.
It's a second review in close proximity. So I think that plays to our advantage. And, you know, so the timeline should be relatively standard to get this approved. I did mention earlier that the guidelines are, you know, something we're quite keen to avail ourselves of. We have to get the data published first. And that's, you know, we think relatively soon, and then we'll submit for guidelines from there. So we do think that having guidelines or being included in the guidelines in advance of an approval could be, you know, quite an advantage for us as the company that has the only approved menin inhibitor with, you know, fantastic data in this space.
Okay. Let's talk a bit about moving this drug into the earlier lines of therapy, both in the fit and the unfit population. So, you know, what do you need to show? Well, first of all, maybe just talk about the studies that are being run in those populations just to set the playing field. What studies are being run in front line in those settings to, you know, to bring this drug into an earlier treatment?
Right. So right now we're running really, you know, a couple of different things. We have a trial ongoing. Well, it's really Beat AML's trial. So this is a group that's working with us. Essentially, this is newly diagnosed patients in combination with our drug and venetoclax and azacitidine. So these are unfit patients, patients not fit for chemotherapy, generally in a slightly older population, highly representative of NPM1 patients, fewer KMT2A patients. So we are continuing on with that trial. There was an update at ASH this past year, which showed, you know, 100% response rate in these patients, which was rather remarkable, again, on top of standard of care and a very high MRD negative rate. So those are two important measures of, you know, how your drug's efficacy is looking.
And I think we've shown on top of standard of care that we add significantly in that population, which is exciting. And I think paves the way for our next trial, which we're going to be working with a group called HOVON, leaders in the AML space. And that trial is starting this quarter. And essentially that, you know, very similar to what we just did. So it's a venetoclax combo in unfit patients with Revuforj or revumenib. And that trial will take, you know, some time to approve patients first. And of course, you know, we have the opportunity to be addressing the highest unmet need in the space, which is on, you know, unfit patients, AML patients, and so in combination with venetoclax. So that's, you know, that's the, you know, sort of cadence.
We have the, you know, we have Beat AML running now, HOVON, and it's getting up and running. And then on the fit side of the equation, which is generally seven plus three plus Revuforj, we're doing a phase I trial now, dose escalation. We should have that data in the second half of the year. And we'll, you know, we'll talk a little bit about maybe, Neil, do you want to kind of walk through, you know, some of that and some of our work and what we plan to do there?
Yeah, sure, so in the fit population, just to add one thing on the unfit, I mean, we will be the first company to initiate a phase III with a menin inhibitor. And as Michael said, you know, that's imminent. We've just been finalizing some details with European, with various health authorities, but so that's imminent. In the fit setting, you know, you have to remember that it's somewhat heterogeneous. Given the activity of revumenib in both KMT2A rearrangements and NPM1 mutated patients, you know, there are different subgroups of patients in the fit setting. What we've demonstrated thus far, and Michael's alluded to this, is the combinability of revumenib with various standards of care, including intensive chemotherapy. As you mentioned, we'll present the intensive chemo combination data later in the year, but we've also presented previously combination data with chemotherapy. We've presented also combinations with venetoclax and HMAs.
In the fit setting, what you can anticipate is multiple studies to be initiated starting in 2025 across different patient subgroups, including KMT2A, NPM1, perhaps double mutant patients, and including combinations with both intensive chemotherapies and other standards of care. The reason that we're doing that is that we view this strategy as the best way to cover all of those different populations, which are, you know, not the same, maybe differences in combination partners. Also, the desire, our desire to get meaningful data into the public domain over the next number of years while optimizing our opportunities for registration both in the United States and elsewhere. Okay.
And just to add to that a little bit, there's a lot of conversation, you know, in the atmosphere about, you know, the potential for accelerated approval based on intermediate endpoints, be it MRD negative CR or CR in the unfit setting. And while we don't discuss our conversations with health authorities, you can assume that those conversations are or will be happening. And of course, you know, if a health authority, be it FDA or the Europeans or the Japanese, were to take a position on accelerated approval or the basic, you know, approvability based on an intermediate endpoint, you know, it's going to apply across the space in general. So we think that we've got a smart, aggressive program of studies because it's our intention to maintain our leadership in the fit patients as well as unfits. Okay. I did get a question from a listener.
I think you sort of addressed it. They were just asking, what are the timelines on the seven plus three combo? Is there a specific reason that we haven't seen that data yet, or that's just the normal prosecution of that study? It's not ready to show.
You know, I think we've been fairly consistent in saying that we'd show data later in the year. We're making good progress. Obviously, I can't talk about the data since we haven't released them, but we're confident that we're well positioned to initiate studies, you know, larger scale studies as I've just alluded to commencing in 2025 in multiple different patient populations. So we're just being. We want to present meaningful data, you know, in terms of numbers of patients treated. But we're very confident in the combinability of Revuforj for the reasons that I alluded to early on. We're also confident about our timelines for initiating larger phase studies, randomized studies in the fit newly diagnosed setting this year.
So are you saying we could see multiple phase IIIs, say, in the fit people in the different genotypes, and then similarly multiple phase IIIs in the unfit kind of NPM1, KMT2A? So this could be like many studies. Is this right?
Let me take the second question first, right? So in unfit, we only need one, right? Which is venetoclax versus venetoclax. That's the study that we're doing with HOVON. That will get us approval globally, assuming that it's positive. In the fit setting, you can anticipate and split it down between, you know, how many phase IIIs, how many, you know, evidence generating studies that we would run, but multiple, right? And we believe that the strategy that we have in place and that we're currently executing on gives us the opportunity to do really two things: generate evidence and release data over the next, you know, several years, as well as giving us options for approval in several of those subgroups of patients.
We haven't. I wasn't specific, but you can anticipate, you know, a range of different studies, both sponsored by us, but also in collaboration with third parties.
You know, obviously a key part of the bold thesis on the story is getting to the front line. How much of an advantage or time advantage do you believe you have relative to some of the competitors out there on getting to the front line market?
We believe we're extremely well positioned. We're moving aggressively. We're planning those studies right now, meaning, you know, actively out there, you know, preparing to start these studies. Can't really comment on our competitors, but, you know, they're clearly behind us. You know, we presented pivotal data now for both KMT2A and NPM1 in the monotherapy setting and, you know, a lot of combination data in other settings with newly diagnosed and relapsed refractory so we feel confident that we're ahead and, you know, we're moving aggressively. We, you know, have the courage of our convictions. We are committed to making sure that we can get revumenib available for as many patients as possible in both the fit and unfit newly diagnosed settings and we think we're best placed to execute on that plan and we think we've got a very smart plan.
I mean, obviously, we'll talk about the GVHD in a minute, but you know, you raised quite a bit of money with the royalty deal. So given this plan to, you know, expand on the phase III in the frontline, do you have the, I know we don't have Keith here, but maybe you can comment just in a very brief way, you know, the funding to do this is a very ambitious plan here to really be the leader in the development in the frontline menin space.
We do. We do. And we'll update our numbers in terms of cash, but I think pro forma, we had talked about $750 million of cash on the balance sheet following the royalty deal. And I think that's, you know, gives us what we need through profitability. And that includes, you know, the work that we need to do, as Neil laid out, to get the front line in the various populations. You know, not all the trials are the same size or take as long. Some are longer, some are shorter. So I think the resources we have in hand today are sufficient to, you know, continue to build our leadership position with a best-in-class molecule. And I should say two best-in-class molecules, right?
So the other, the Niktimvo, we'll talk about in a second, but I think this is, you know, a very interesting deal that we did at the right time in order to make sure we had sufficient resources to deploy in the way we thought would generate the best returns for shareholders, so I think that's, you know, really what we're trying to accomplish, and last year was very important doing that and bringing that capital to us.
And then just sort of one more on the front line, Neil, you know, in terms of the timing for getting a little bit more clarity or just details on exactly which trials and when they may start and designs. And you spoke about the meeting with the regulators and having some potentially, you know, intermediate endpoints that could be registrational. When might that all get, you know, tied up in a neat package to present to the markets so we understand the at a more granular level? Is that something that we could expect this year or that's going to take a bit longer?
Yeah, yeah. No, no, you can expect, so because it's an ambitious plan, you can, number one, you can expect to hear more from us this year, later in the year. Like I said before, we don't discuss obviously our regulatory interactions, but you can rest assured that those are happening, and we think it's important for those to happen, right, as we finalize the plan, but our intention is to start initiating multiple studies this year, and therefore, you know, if we meet that plan and we're committed to meeting it, then, you know, the details will be out there. It may be that some of the other additional details, because we will prioritize our portfolio of trials, some of the additional details may follow into sort of early 2026, but you're definitely going to hear from us later this year.
Okay.
I just add, you guys. I think, look, the competitive nature here of the market and what, you know, we are in the lead. We do believe we have significant advantages, not only in time, but also based on the molecule, and so it's something where we want to be pretty careful about how we bring the information out at the right time. When we're ready to kind of get going on a number of these trials, we'll have more to say about it, but we're keeping it a little bit close.
Okay, so let's shift over a little bit, and by the way, for anyone who may have joined late, you're happy to take questions. Just email me at my email and I can relay the questions, so we started talking a little bit about GVHD. You know, you kind of gave the high-level rationale for why the royalty deal now. Anything else you want to add to that or we can get into more of the clinical stuff?
Yeah, look, it was, you know, a really important deal for us. I think, unfortunately, the asset has been underappreciated by the market. And, you know, we think this is a very significant opportunity, market opportunity, a growing opportunity. We have a, you know, an excellent partner in Incyte in that, you know, they really have built this category. And so we're going to, through our deal with them, leverage what they've learned and what they were able to do with Jakafi. So I think Royalty Pharma, as a leader in the field, you know, came to us and we had, I think, a fantastic alignment on value. So if you think about this transaction, not only provides $350 million of upfront capital, but also the royalty rate at 13.8% in exchange for the $350 million is capped at 2.35 times.
There's an opportunity not only to have the cash come in now to monetize part of the royalty, but not the entire amount. There is an ongoing, what we think, quite significant revenue stream because of the, I call it, modest, you know, well, high-margin business that this is, to be able to have an ongoing revenue stream from the product, even sharing some of that with Royalty Pharma. Ultimately, as we expand to, you know, earlier line patients and chronic GVHD, and then even to IPF, I think there is, you know, a lot of upside in this product. You know, we will share in that meaningfully and with the cap for many years. We have the ability to really capitalize beyond what we pay back to royalty.
So I think it's, you know, in our mind, a very well-conceived transaction at the right time and really allows us to build this franchise the way we expect to as well, you know, bring the requisite capital to bear for Revuforj. So I think we're in a, you know, an excellent position with that compound. Really, I think the market resets the value. Because if you think about what Royalty did here, they had a quite significant and robust view of the product in order to get a deal of this magnitude done. So it aligns very nicely with what we've always thought the product could do. You know, it's a multi-billion-dollar opportunity. But, you know, I think the market has sort of misunderstood that.
I think you've done a very nice job in highlighting this as an opportunity for us, but it's completely underappreciated in the value of our stock at this point.
The other interesting kind of wrinkle on this, and you can tell me if I got the math right, but I mean, with the 2.35 cap and the fact that you've got big plans to do IPF and you're going to have some data, I think, in a couple of years, is it correct that, I mean, or is it a fair assumption that by the time IPF is there, that you're going to be done with the cap?
Quite possible. Yeah. I mean, it's quite possible that that could be the case. I mean, I think, look, the product, we think the product could do north of $1 billion peak in chronic GVHD alone. And based on that math, you may be correct, Yigal. So I think there's that. And then I think the IPF indication. Well, there's front line and combinations that we're running in GVHD. So that really builds to get to those type of revenue numbers. But then I think when we get to IPF, that's a whole, you know, different opportunity with quite a lot of unmet need. And we think we can bring a new mechanism. And if we're successful there, it could be quite meaningful as well. So that's what I was getting at earlier, is a lot of upside in that franchise.
Okay. So let's talk just more specifically then about the near term for a moment. This one, you may be able to say even less because Incyte is kind of running things a little bit more. But what can you tell us now that you've got the different profiles or, you know, the nine and the 22 milligram, you've got everything lined up to do this, to do the launch. What can you say about the very, very early days, literally, I guess the last several weeks, perhaps, or?
Yeah, the product was approved in January, and we started selling in late January. So, you know, it's just very early days. And I think we're off to a good start. You know, it's sales teams, you know, Syndax and Incyte, both working very closely together, you know, speaking to physicians and bringing the product out there, making it available. And I think there's been a lot of interest in this new mechanism. The data was extremely strong in GVHD. And remember, we were treating patients that had an average of, you know, four years of prior therapy, and we're not satisfied. And we were seeing sort of best-in-category results. So again, a very important new mechanism, we believe, that will really, you know, be accepted well by physicians. And that has been the reception so far.
We're just getting started here, but every reason to believe that this is going to be a solid launch as well.
Okay. This next one, I was about to ask an investor also emailed me essentially the same question, just related to the structure of the deal so we could just understand the operation of the, how does it work? Can you just walk us through the economics with Incyte? You know, who books the sales? At what point is there a trigger where, you know, you start booking sales? Or just walk us through how this whole thing, how this works. Is there some threshold number that we need to know? Just help us with that.
Yeah, no, no. Well, the way that it's actually quite simple. So it's a 50/50 profit and loss split in the US. ex-US, it's a license to them, so they pay us milestones and royalties. But let's just focus on the US as a 50/50 profit and loss split. We co-promote, you know, they have a 70%, we have 30% in terms of rep time and effort. But just in terms of the P&L, they book the sales. And expenses will be, you know, sort of deducted as you think about a joint P&L, expenses on the program will be deducted. And then on our P&L, you'll see a revenue contribution after expenses that will flow to us. And but it is a 50/50 split, right? So we split after expenses 50/50. And that will be, you know, represented on our P&L as a revenue contribution from the partnership.
So quite simple.
Okay. And then below that, you do the royalty. And then there's another, there's some other, I think there's some other royalty, right? Just another party, isn't that correct?
Right. We licensed the program originally from UCB, so those royalties are paid out of the collaboration, so it's split between, you know, equally between Syndax and Incyte. Development expenses, just to remind people, development expenses in the U.S. are split 55% Incyte 45% for Syndax, so there is some leverage there for us, but in terms of the product revenue, I just went through it. It's pretty straightforward.
Okay. So similar kind of conceptually in that you're launching in the later line, but the goal is to, you know, advance this product to an earlier line. So tell us about what you're doing with Incyte to advance that thesis. Obviously, the Jakafi combo is a critical one, but are there other plans to, you know, bring this into an earlier line?
Sure. Neil, do you want to jump in?
Yeah, sure. So in fact, there are two frontline studies that are now ongoing. One is the phase II in combination with ruxolitinib, which is designed to de-risk that combination, right? Establish the feasibility, which we fully anticipate will go, you know, will be relatively straightforward because axatilimab is, as you know, pretty well tolerated as a monotherapy. And we optimize the dose well in that regard. So establish the feasibility. And then basically determine, right, the working hypothesis is that the combination will be more efficacious than ruxolitinib alone. And therefore, the primary endpoint of that trial is, or are six months. So it's to de-risk the move to phase III , position us, our partners for the end of phase II discussion with the agency and move quickly to phase III.
In addition, there is a phase III ongoing against corticosteroids, and that is now active, right? So it's basically covering two different groups of patients, totally upfront, and then patients who would be indicated currently for monotherapy ruxolitinib. And in that way, it covers, you know, quite a broad population of chronic GVHD patients earlier on in the course of therapy, as Michael alluded to also early on.
So the steroid one, what's the exact design of the steroid one?
It's a randomized phase III.
Okay. And it's just A versus B, steroid versus, okay.
Yeah.
And so the timeline on that one?
What I can say without sort of having memorized Incyte's guidance is that primary completion in the public domain is sort of mid-2020, primary completion sort of mid-2027 as listed on clinicaltrials.gov. I'm not sure that Incyte has guided beyond that. I know that we haven't.
Okay. Now, the other interesting feature of the development plan is, I believe there's work being done on a sub- Q. Where do things stand with that? And how important is that? I mean, obviously, you know, the competitors, well, your partner too, but also competitors, Rezurock, Imbruvica, or oral, like how much does the sub- Q matter? I mean, we've heard when we talk to KOLs, you know, they're very, very supportive of the mechanism. They think it plays very well complementarily with the other approaches. The only thing we do here is that, you know, it's not oral, so.
Right. I mean, I think maybe I'll make a comment, Neil, you can add on. But I think it's always helpful to have options, right? I think the most important thing in this category is, you know, making sure the drug works well for these patients and, you know, obviously is safe and well tolerated. But patients need new effective options. And this is a new mechanism. So, you know, IV, it's a 30-minute infusion. They're not sitting in an infusion center for, you know, hours. So it's quickly done in the doctor's office or in an infusion center. We don't hear that it's going to be a barrier at all. That just hasn't been, you know, hasn't been received that way. So I think we feel like this is, you know, an opportunity to expand how we deliver the drug.
And over time, a sub- Q could be useful for earlier line patients, perhaps could be on it for quite some time, you know, months, if not years. And, you know, potentially even in areas like IPF, right? And so I think we're looking at these options as just that, you know, an expansion opportunity, but not a prerequisite for utilization by any means. And I think, you know, these are high-touch patients too. Physicians tell us that they really, really like having, you know, access to them on a regular basis. So for them to come into the office to see them and be evaluated and get an infusion every few weeks, that seems like good general practice to them. And good for compliance too, because remember, oral medicines aren't always, you know, their patients aren't always 100% compliant.
So I think on balance, this to us, you know, sounds and feels like, you know, just the right next step, having additional options with the sub- Q, but it's not here and now, not critical.
Maybe just a quick technical add, because I think you asked how it was going. It's going well is the answer. It's technically very feasible, and therefore, you know, progress is, you know, we're making good progress.
Now, of course, IPF and then even more generally, just any fibrotic disease, I mean, that opens up another level of market opportunity, you know, orders of magnitude more than chronic GVHD. So, and you're going to have some data, correct, in 2026, I believe. What are we going to get there and what needs to happen in that data set to make this phase III asset?
Go ahead, Neil.
Yeah. So we're currently running a randomized phase II trial with 135 patients randomized two to one. The primary endpoint is FVC, right? The annualized rate of decline in FVC, which is the approvable endpoint, right, for a phase III study. So we designed the trial, you know, in that way so we would de-risk a next decision point of going to phase III . And it's designed, you know, within the confines of, you know, it's actually a big proof of concept study. It's not a phase III study, but it's a big proof of concept study. And it's designed to inform us around that endpoint that, you know, axatilimab, when administered in the background of standard of care, will slow the rate of decline of FVC, which would then effectively set us up for, you know, the same study in the phase III setting.
As you alluded to, Yigal, we've guided that we'll have data from the trial in 2026.
Is there any way that that could form the basis for some sort of accelerated approval that's not in the cards?
I think that you never say never. I mean, if the data were incredibly dramatic, and you know, we know from chronic GVHD that patients with severe lung disease really benefit extremely well, including patients with bronchiolitis obliterans, but I think it would be unfair to set that expectation. You know, I really do. I think that it's a phase II trial, and assuming that we have very robust data, it really de-risks the next development step, but it would be unfair to set that expectation.
That one is being done with Incyte? Or what is the?
We're actually executing that trial.
You're doing that one. Okay. Okay. And Incyte, do they have any rights to that indication or how does that?
The way the partnership works, you know, either party can move forward with a particular indication of interest with or without the agreement of the other party. I think we align very nicely with Incyte across indications that we'd like to pursue, some of which we haven't announced and thought deeply about. Others we have, such as IPF. IPF was on the list when we got into this partnership several years ago, and I think, you know, our view was we wanted to run this proof of concept trial. And so I think based on the results of this, you know, Incyte always has the opportunity to opt in. And so there's, you know, there's a mechanism in our agreement with them that ultimately there will be no mismatched economics down the line.
So you get to a certain point and the parties either have opted in already and come together on costs or they will be, you know, made to do so at approval. So I think there's, you know, good alignment. And IPF is obviously a very large indication of interest and, of course, a new mechanism being studied there. So assuming that the data is positive, I think, you know, this, you know, I don't want to speak for Incyte, but I would imagine they'd be interested in doing this with us and continuing. But so they have, just to answer your question, there's no splitting of indications here. Everything is within the partnership.
You just may get too in the weeds and investors asking, but can you comment at all on what delta, what you need to show on the primary on the FVC for the study to work?
We haven't sort of commented in detail on the statistical design beyond what I've said, which is the sample size and the primary endpoint, but we haven't delved into the statistical studies.
Okay. All right. Well, we're quickly running out of time, but let's, obviously the priorities are the two launches and, you know, some of the earlier studies you've referenced. Is anything happening, or I shouldn't say is anything, I mean, I'm sure there's something happening on the BD front, but is there a lot happening on the BD front or is it more of like a, you know, tertiary goal?
Yeah, no, we are, you know, quite interested in business development. I think that's the lifeline of our company. And we've built the business that way in licensing products. We've done it over our history three times. And of course, these two products are approved. Our other product, entinostat, actually was approved in China. So we've had some success in bringing in additional these molecules. And so we want to make sure that they are and remain our priority, entinostat, I mean, Revuforj and Niktimvo as our priority. And obviously the resources are deployed there. But I think long-term interest in keeping business development going and making sure that we have the ability to add molecules to the portfolio. I think that is something we often think about.
I think, you know, the truth of the matter is it's an exercise that we keep a very high bar for. We're not willing to just bring in any molecule. We are interested in, you know, oncology really only and targeted therapy at that. I think that's an area we know well, and from a resource perspective, seems to align nicely with early results are relatively meaningful. And so we've been successful in following that paradigm and we expect to follow it in the future. Again, early stage assets has been where the focus has been, and so we continue to work hard to try to find new things that are of interest and fit in well with our overall priorities of the other two molecules.
But it sounds like you're not really setting any sort of concrete expectations for sort of, you know, X number of assets and Y number of years or something like that. It's more opportunistic.
Yeah, no, I think that's fair. I think it's fair, Yigal. You know, I think this is, it's too difficult to, as a company of our size, to find assets that we think are highly valuable to look at it in a way that's, you know, kind of more specific than that. I mean, we have our own internal metrics. We haven't, you know, talked about that externally, but I think there's interest in adding new molecules. It's just, we're not willing to settle, right? So I think we have to be, you know, quite conservative in our approach.
Okay. So I guess, you know, as we're wrapping up, you've, you know, done extremely well with the trials with the FDA into very different areas. I guess the last question, big picture, which you can anticipate is, you know, what is everyone, what is the market missing with the story? I mean, you know, obviously the stock, you know, I think based on my work should be a lot higher than where it is. I think you would agree. So, you know, what's the disconnect?
Look, I think this, you know, unfortunately the market is the way it is. And that's been a challenge for many companies, not just Syndax. I think in our particular case, we're unique. We're unique in a, and I think a very special way that people don't appreciate. We have two approved products. And we are right, you know, in the midst of launching these products. The markets are significant. We have first-mover advantage. We think they're going to be multi-billion-dollar products. I think people aren't appreciating that and what it could mean in terms of value, not five years from now, but we're talking immediately, right? So bringing these products, we think we have the capital required to build a very significant business. And so there's a lot of growth that's just being missed by the market.
I think people look at new product launches in our space and they perhaps have a very conservative view on that in terms of, you know, generating revenue and creating value. I think our view is we're just starting and we're feeling quite good about where we are, but the value of the company from this point forward should accelerate quite nicely. So I think they're just missing perhaps the point in time that we're at and the fact that we have these two, you know, very unique products and a really experienced company. We're not just a new commercial company in the sense that we have new products that we're launching. We have very experienced people who know what they're doing. And so I think we'll execute quite well. So I think that's it. I mean, it's just a disconnected time. I think ultimately this should build quite nicely.
All right. Awesome. Well, thank you both. Fascinating stuff. We look forward to the ramping trajectories for both products and then the clinical data for the variety of studies we mentioned. So thank you and very, very good to talk. And just as a reminder, the next session will be at 10:00 A.M. with my colleague Geoff Meacham on GSK. So thank you all so much.
Thanks, everyone.