Welcome, everyone, to the JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad: Malcolm Kuno, Priyanka Grover, and Rathi Pinhasi. Our next presenting company is Syndax, and presenting on behalf of the company, we have CEO Michael Metzger. Michael.
Great. Thank you, Anupam. Great to be here, as always, back at J.P. Morgan. Exciting time for us, exciting time for everyone. So thank you. Let's get started. Forward-looking statement. You should refer to our website if you'd like to look at it in more detail. We will be making forward-looking statements today. It's just a reminder. So Syndax is in a very unique, and I'd say enviable, position to have two first-in-class, best-in-class, practice-changing medicines with really significant potential. We had a major year, and a lot has changed since I was up here last year at J.P. Morgan to present to you. We had two major milestones that I'll call out: approvals of two major medicines within 90 days of each other, which is, for a company our size, rather remarkable.
We owe a debt of gratitude to our people at Syndax, our collaborators, those who contributed to our success over the last year and for many years, frankly, to bring these medicines forward. And we're especially excited about what these medicines can do for patients, and we're just getting started. So let me run through some of the milestones here. So we launched our first, we got approval and launched our first and only menin inhibitor in relapsed/refractory acute leukemia with KMT2A translocation in the U.S. It's called Revuforj. It was approved in November of this year, slightly earlier than the PDUFA date of December 26. So that was in the middle of November, a very exciting time for the company, first-of-its-kind medicine. We'll talk about that today.
And then we had pivotal data with the same molecule with Revuforj for NPM1 acute leukemia, relapse refractory, first-of-its-kind data in a pivotal trial. So very exciting. I'd call it one-two punch, if you will, where we have approval in a first indication in an area of very high medical need, perhaps the most high medical need in acute leukemia, followed by a very large segment, NPM1, which we expect to file an SNDA in the first half of 2025, get the drug approved, hopefully before the end of 2025 as well. So those are very important, exciting developments. And then, of course, Niktimvo, our second program, it's a CSF-1R anti-CSF-1R antibody for chronic GVHD. That was also approved in August of 2024. Very exciting, first-of-its-kind new mechanism for these patients who have chronic GVHD.
And we will be bringing that molecule to market, hopefully in the next few weeks here. The clinical development for both of these molecules continues as we really take our first-mover advantage and drive it forward into earlier line settings. Lots to do, lots to accomplish, and we're excited to do it. We are set up to do it with pro forma $750 million in cash. We did a royalty transaction at the end of last year as well on Niktimvo, which really set us up for success in order to drive the molecules forward. We are, as we said, funded through profitability, so no need to raise additional cash. So very exciting time for the company. I'll talk a little bit first about the menin inhibition space and where we're really poised to lead.
It's a new modality for patients who have a specific genetically defined set of leukemias, really the largest subset of leukemia that is targetable today. As I mentioned, menin inhibition is an exciting new class, has multi-billion-dollar opportunity associated with it. About 50% of the patients who have AML, whether they have KMT2A or NPM1 or something called NUP98, there are other potential lesions that could be susceptible to menin inhibition. 50% of the patients could be targeted with a menin inhibitor. Specifically, Revuforj is the first approved. That translates to about 15,000 patients in the U.S. and about a $4 billion opportunity as well in the U.S. The relapse refractory population is a subset of the $4 billion. We are poised to lead, and we are in a unique position to do so. We have the first and only approved menin inhibitor. Why is that important?
It's important because we're starting in an area of very high unmet medical need where physicians need something for their patients, and they have the opportunity to use our drug first. It gives us competitive advantage. Physicians have the ability to utilize it and to create a very high bar for the next generation or even the next molecules that may be available but not differentiated. So we're creating a very high differentiation in the marketplace. It's also a highly differentiated profile. We've seen data with our molecule across the patient populations: AML, ALL, adults, pediatrics. So we have the broadest coverage to date with a very, very broad initial label. So we feel that that really differentiates us in the marketplace. The near-term opportunity I mentioned, our second indication for NPM1, that comes on the heels of our first indication.
It's very unique where you have two indications coming pretty close together. Usually, you have to wait years in order to get a second indication, but in our case, same physician audience, and frankly, we have the opportunity with new data to get into guidelines early, even before we can get the drug approved, but it's all in front of us, and it's near term, and we're poised to deliver combination data in the front line. We've done that across a bunch of trials. We'll talk about some of them today, but we are poised to get there first and build on our formidable lead in this category, so we feel really well set up, and these are our strategic priorities going forward, and we are executing, we think, very, very well in order to first secure our first-mover advantage, and that's where we'll start. Let's talk about that first.
Once we're through that, we'll talk about the expansion into other opportunities. So here's the drug. It's available in three dosage strengths on the label: 25, 110, and 160, rather. It is an oral pill, as you see. It's approved for a very, very aggressive form of leukemia in KMT2A. There is high unmet medical need. These patients are easily identifiable. The cytogenetics are done when they're diagnosed, and physicians are very well aware that they exist in their practice, and that accrues to our benefit because patients are identified by the physician, and we can get them on drug quickly. There is this urgent unmet medical need. There's nothing in standard of care that seems to work very well for them, even chemotherapy. If it works, it only works for a short period of time, so there is this urgent need.
It is a broad indication on our label, as I mentioned. It includes both pediatrics and adult patients, and we have this first-mover advantage where we can really build on the early success of the molecule without having to compete with standard of care or even compete with pipeline programs that are coming behind us. It is a unique situation in this market where we can really own all of it and satisfy a large patient need. We got started well in advance of having the drug approved, got started with pre-launch activities, setting the foundation for a very successful U.S. launch for Revuforj. We hired a really experienced team, an average of 22 years of experience, multiple drug launches. It was critical, has been critical to our success. We profiled accounts.
Our customer-facing people have been in the field profiling accounts, made thousands of calls to physicians leading up to the launch of the drug, even getting into their offices before we had the opportunity to get the drug approved, so this was an educational effort to get them to understand that a new drug was coming and what the unmet need was. I think this was met with a lot of enthusiasm. We were also able to educate payers, the vast majority of which we were in front of before the drug got approved. We built a very significant and dedicated patient support program and distribution network, and lastly, we built data analytics that allow us to really proactively identify patients and meet them at the physician's office, really identifying them with good cooperation of the physician.
So we've done everything we can to be in a very good position to launch this product. And today we're here. We launched the product, as I mentioned, in November. We had actual drug in the channel within five days. That's industry best. That is very good practice. We've seen scripts being written, and this is early days, but we've seen scripts being written not only from the largest institutions, major academic medical centers, but also community practices, which is a great sign for a launch of a new medicine. We've seen reimbursement across the different payer types. So it's not only commercial reimbursement, but government reimbursement as well. And importantly, we were added to the NCCN guidelines rather quickly. So I mentioned drug approved in mid-November, in NCCN guidelines by mid-December.
Of course, we went to ASH this year, and there was a groundswell of interest around our program, around menin as well. All of that accrued to our benefit as we've gotten out with the only menin inhibitor with great data. Physicians are excited about what the profile looks like. They think the drug is easy to use, and we're finding patients. Off to a great start. We'll update, obviously. We haven't put out any numbers yet, but you'll see at our upcoming quarterly calls, you'll see an update. We're excited where we stand today. Let's talk about the expansion beyond the first indication into NPM1, which is, as I mentioned, a big subset. It's about 30%-35% of all AML. Last year, in the midst of getting the drug approved, we also had our first positive data in NPM1.
This is the first data of its kind in a pivotal trial, 64 patients. Overall response rate 47%. CR/CRh rate at 23%. Again, heavily pretreated population, relapsed/refractory, MRD negative rate 64%. Very positive data, very strong showing for the molecule in this setting. Many patients going on to transplant, and this is an older population, older than what you see with KMT2A. To be able to transplant these patients is a very positive outcome. We actually updated that data set. There were some patients that were available that came online a little bit later. At ASH, we put out additional patients, increasing the size from 64 to 77 patients. Overall response rate, CR/CRh very similar. It went up to 26% on the CR/CRh rate. This essentially is the data set the agency will look at. They will look at the pivotal data set of 64.
They'll have additional analyses on the 77. So again, very consistent and robust data set. In the first half of next year, this year, rather, the plan is to publish the pivotal data set and submit to NCCN guidelines. So once you have an approved agent, you can submit on a publication to the guidelines, which we believe help drive additional utilization in the second indication. We'll also, subsequent to that, submit an SNDA to the FDA for approval in NPM1 acute leukemia. And of course, the potential for an FDA approval at the end of 2025 as well. So that is our plan to drive value in NPM1. I will say that as of today, as of now, we've seen not only good uptake, and we're seeing utilization across the board in patients with KMT2A, but we're also seeing some interest in NPM1 as well.
That, of course, will accrue as we get the drug approved into guidelines. All right. So let's talk about moving to the front line, which is sort of the next frontier for this class of medicines, especially for Revuforj. So our strategy has been to go where the highest unmet medical need is in AML. And we've pursued that in relapsed/refractory. As I mentioned, we have one approved indication. We'll have a second indication shortly, we hope, in NPM1. But I think the front line setting is the next frontier. And as we think about starting trials, we're addressing first the highest unmet need through our trial with the HOVON group. It's a global trial that we will start and initiate for unfit patients. So these are patients who take Venclexta, and that's the standard of care.
This will be a trial I'll describe in a moment that evaluates whether we can add to that doublet. So that's our first foray into front line. And we'll also be evaluating on the fit side of the equation. These are patients who are fit to withstand standard chemotherapy. And we're doing trials now to look at that population in a phase one. We'll be expanding to additional phase two trials in combination with chemotherapy. The idea is that the unfit and the fit population are not the same in the sense how standard of care works is actually quite different. What they receive in the front line is different. And our approach has been really to prioritize addressing the populations with, one, the greatest unmet medical need, two, get speed to data. You want to create as much data as possible in order to inform the practice of medicine.
We believe that our trials will do that over the next handful of years and build a regular cadence of potentially practice-changing evidence as well. It's a robust strategy that we look to employ in order to get the drug not only approved in these settings, but also supported by evidence and into guidelines. These are the two trials, the foundation trials that we've been working on, and we've presented data this year at ASH and at our ASH event. They are investigator-initiated trials. We work closely with these investigators. The first is the SAVE trial, which is being conducted at MD Anderson in relapsed/refractory patients. The second is the BEAT-AML trial, which is in newly diagnosed patients. Both are in combination with Venclexta. The SAVE trial actually utilizes an oral regimen, so oral decitabine. In the BEAT-AML trial, we're using azacitidine.
You see here that relapsed/refractory on the left, the overall response rate in the SAVE trial was 82% in 33 patients. The CR/CRh was 48%. MRD rate was 65%. The drug adds quite a bit of efficacy to what you would expect from ven and aza in the relapsed/refractory setting. This regimen was extremely well tolerated. Patients stayed on a considerable amount of time. That data set is building and now enrolling in the frontline in newly diagnosed patients as well. This might be an opportunity to register the drug. We'll wait to see how this data matures. The BEAT-AML trial is a very important trial. This is the foundation for what we were doing with HOVON, I mentioned before, for a pivotal trial in the unfit population. As you see here, the data speaks for itself.
100% overall response rate, CR rate of 95%, MRD of 95%. So we're basically maxing what seems to be maxing out efficacy in this population, and the drug is extremely well tolerated. We'll be continuing with both of these trials over the next several months. And into this year, we'll have some updates, hopefully available to keep informing how these regimens work. So this is the unfit population trial that we're conducting. This is the trial that we're doing with HOVON. It's a rather large trial, 415 patients, placebo-controlled, randomized one-to-one. Historical Venclexta results, overall survival is the endpoint. The overall survival in the VIALE-A trial was 14.7, so that's what we'll be comparing to. This is an area of very high unmet medical need. We'll be enrolling the majority of our patients will be NPM1 patients. We will be allowing KMT2A patients in the population.
But keep in mind, unfit patients, or I should say KMT2A patients, are generally fit. That's why this population is being enrolled this way. But this gives us probably the fastest route to the front line, and we are considerably ahead of any competition to get there. On the fit side of the equation, on the right side here, we have 7 plus 3 plus Rev data accruing. We'll have an update for you this year. We're also including some maintenance in this trial to look at the effect of maintenance for this population. So we have data coming, and that will inform the number of trials that we're going to be starting in 2025 to satisfy various pieces of the fit population. All right. So this is a depiction of the market. We've had a lot of comments about how big is this market?
We see this as a $4 billion market broken down to relapse and relapse refractory first. About 2,000 patients are KMT2A. About 4,000 patients are NPM1, so about 6,000 patients in the relapse refractory setting, accounting for our price point at $40,000 per month thereabouts and duration of therapy of roughly nine months across the different segments. We see this as a segment that could yield up to $2 billion in sales as a TAM. So that is, we think, a very significant opportunity, one where we are ahead and have the broadest opportunity in front of us without significant competition for some time. And then, of course, the front line addresses about 9,000 patients overall, and that's what we're starting to address with these other trials that I just mentioned. So I think this is an opportunity for us to be the largest targeted therapy that you've seen.
You've seen targeted therapy, IDH inhibitors, FLT3 inhibitors. This is a larger segment than those. In some cases, about twice the size. If you think about IDH inhibitors, about twice the size of what they've achieved in this setting. And so we think this is a very distinguished opportunity that we'll be addressing with our first-to-market strategy. All right. So let's talk a little bit about CSF-1R inhibition. This is a second molecule targeting. It's a novel mechanism targeting inflammation and fibrosis, which is unique in chronic GVHD. And we have potential to expand beyond the first indication. So as I mentioned, the FDA approved the drug in August of last year, and this is after two prior therapies. So this is what we call a third-line indication. The drug is already included in the guidelines, which is fantastic.
In fact, we actually have a J-code that was assigned, a permanent J-code that was assigned in the last day or so. So that is a very good sign for this agent. We're preparing for launch in the next few weeks here, waiting on the FDA to approve a few new vial sizes so we can get those into the market. But the objective here is really to establish Niktimvo in the third line and then ultimately advance into earlier line settings. We have a partner at Incyte. We're privileged to be working with them. They've done a fantastic job, very experienced in this field, as you know. And they are driving two new trials to expand into the earlier lines of treatment. The front line combo trial with Jakafi has begun, a phase three combo trial with steroids as well.
Ultimately, what we'd like to do going beyond GVHD into other indications is something we're quite excited about, as well as our partner. Syndax is driving the IPF trial, which we started last year. We should have this IPF. It's a randomized phase two, should have this fully enrolled this year with data in 2026. A very exciting new expansion opportunity where we think the antifibrotic nature of the drug should play very well in a new area such as IPF. I just wanted to mention that we did a royalty transaction. I mentioned it earlier, but we did a royalty transaction at the end of 2024, which was very significant for a number of reasons. There was a $350 million upfront payment working with Royalty Pharma, who we think is a very strong player in that business, understands how to do this.
The payment was $350. The royalty's 13.8 capped. It's on the net sales of U.S. sales. It's capped at 2.35 times, which is important. We have an ongoing royalty revenue stream, rather. We haven't given it all away as a royalty. So we have a very meaningful share on the ongoing revenue, and so it builds over time, but ultimately, we believe this will be a big product and the royalty will be paid off and will go away entirely, so we have ongoing revenue and we have upside through this deal, but important to mention, the valuation reflects multiple factors. It reflects a very significant patient population, 17,000 patients in the U.S. Most of these patients require ongoing treatment for potentially many years. There is high unmet medical need in this space. It's a large growing market.
So we have another peer agent that launched a couple of years ago. It's doing in its third year sales over $500 million as a third-line agent. We have the ability to do just as well and grow the market. It's a differentiated profile with a new mechanism that deals with both inflammation and fibrosis. The data that we have thus far is as good in the category as we've seen. As I mentioned, we have a strong partner. And we have all these opportunities beyond GVHD, namely going into earlier lines of therapy as well as expanding to indications such as IPF. So I think it's important that as you think about our story, that you don't sleep on Niktimvo. It's a very important medicine I think will do quite well, and we're excited to get going. All right.
So looking ahead, just to mention our milestones for the year, call out a few of them. Submitting the SNDA and publishing the data from the NPM1 trial are very important. Why is publishing the data important? Because it facilitates our getting into guidelines ahead of approval. We will submit the SNDA with potential approval by the end of the year. Obviously, very important for Revuforj and for Niktimvo. Launching in the US in the next few weeks here will be a very good start to the year for that molecule as well. So those are some of the important upcoming milestones. And so I think, as I summarize here, we are poised and positioned for really long-term growth. We're a unique company. We have two commercially available products, so we will have the second one commercially available quite soon. A lot of growth ahead of us.
We have two first-in-class therapies. Both have billion-dollar-plus potential and markets that support that. We're leading in the menin space. As I mentioned, we feel like we have defensible, we have a defensible position, and we will be growing based on a mountain of evidence that we're accumulating, clinical evidence that is. And Revuforj is positioned for a unique trajectory of launch. We have a first indication, and we have a second indication close behind it. And in GVHD, we are poised for success. We have a fantastic partner. We have a unique molecule that can do very, very well, and we plan to get out of the gate quickly. We have a clear path to expand utilization by building in new indications for both molecules. So we know exactly what we need to do, and we're well capitalized to do it with $750 million funded through profitability.
Lastly, I'll just mention the leadership team at Syndax and the group of people who have worked as employees of Syndax for a long time. We're dedicated to this. They've done remarkable work, and I'm grateful for them every day. So thank you all for your attention today, and I'd love to open it up to questions.
Thanks, Michael. I just want to remind folks there's kind of three ways to ask a question, right? There's the old-school way where you raise your hand and I'll call on you. You can send the question in the question portal, and I'll read it, or just email it to me, and I'll ask on your behalf. Michael, maybe I'll just kick off here with, for Revuforj, you mentioned IDH inhibitors. How are you thinking about any analogs that you might comp this launch to that we should be considering?
Yeah, it's an important question. I think analogs are in this space maybe a little bit hard to come by, so I'm going to present it this way. I think IDH inhibitors address (and they've been out since the early 2020 or 2021) they address probably 20%-25% of AML. They've done about $400-$450 million in the U.S. Most of that is almost entirely relapse refractory. If you think about how we would use that as an analog, menin addresses probably 40%-50% of AML, so double the size of the IDH inhibitor market. And if you size that up for price, so we price our drug about $40,000 a month. They're priced at around $32,000-$33,000 a month. So if you think about that and you size it up for price, it's about a $1.5 billion-dollar category for relapse refractory.
I think that's probably the most simple way to think about it. They also have been, frankly, hampered by the use of Venclexta. When they were approved, Venclexta was approved as well, and Venclexta works well in these patients. So they never really received the lift-off, if you will, in the trajectory of their sales. We don't have such an encumbrance, right? So we have KMT2A. There's really nothing that works in KMT2A, and we have the whole market. NPM1 will be first, and we think we have a very strong position there as well. So we have the opportunity to be larger than that. And as you think about the component of putting patients back on, we're driving a lot of patients to transplant. Being able to put them back on therapy post-transplant really will elongate the duration of therapy.
So I think that gives us a lot of upside and support for our $2 billion TAM in the relapsed/refractory setting.
And look, I know it's only been a couple of weeks since launch, and you said you'll give us a lot more detail on the Q4 call. But just wondering, any initial learnings anecdotally from the early innings of the launch?
Yeah. Thanks. I mentioned some of them earlier. We're off to a great start. I think the patients or the physicians like the profile. They find the drug easy to administer. They can find patients, right? We're seeing patients get on drug. We were in the channel within five days, which is fantastic. We're delivering drug to patients quickly. So the experience, the dedication of our commercial field team and our field medical team is clear that we're able to really drive utilization. I think you want to see payer coverage. Obviously, the formulary will build over time, and we have probably a couple dozen payers that have already started to cover the product. The drug's getting paid for, right, which is fantastic. We're seeing scripts being written not only in the academic institutions but also in the community.
Usually, you don't see community come online quickly, but in our case, I think getting out there, being prepared for this launch has paid dividends. So I think both of these things are good indicators for us that we're building well, and we'll continue to see the fruits of our labor.
Questions from the audience? Yeah.
So could you maybe speak to a little bit of what you're seeing in terms of how being the first mover in KMT2A is, if it's making doctors more comfortable in terms of how they're viewing the drug in NPM1?
Sure. I mean, I think they seem to be very comfortable. I think the data, the proximity to our approval to the second dataset coming out, right, at ASH, was very helpful to us. It really was an educational opportunity for us to get in front of them with new data, and it's very consistent data with what we've seen with KMT2A. So I think we are in a unique setup in the situation where they're reaching for the drug for KMT2A, but it's the same physician, right? They're also treating NPM1, and there's high unmet medical need in the relapse refractory setting for NPM1 as well. So I think there's a natural tendency to say, to get comfortable and really build an experience set with KMT2A and then look quickly to prescribe it for NPM1 as well.
Questions from the audience? Yeah, Alana.
Can you talk about how you're seeing that your GVHD drug will be used? I mean, because there's multiple drugs in that space, and the question is, do you start? Even though you start on third line, will there be alternating drugs, or what is your understanding of that?
Yeah, thank you. Great question. So GVHD is an illness where patients stay on drugs. They rotate through different drugs over time. You know that. So I think there's no set line of therapy often. We know that steroids are given to the front line. We know that Jakafi is given in second line. Our drug will be given in third line. There's a rotation. There's an opportunity to potentially get the drug earlier if a physician wants to write it that way. But patients tend to see multiple therapies over time. So once they stop responding to a certain therapy, they go on the next therapy. This is a unique mechanism of action. It deals with both the fibrotic aspects of the illness as well as the inflammatory aspects. We haven't seen that with other drugs.
So whether the drug gets used ahead of our competitor in the third line, so to speak, or after, we've shown in our data it doesn't matter. Patients respond well. They stay on therapy. In our trial, we treated patients who had been on therapy for four-plus years on average, and they still had best-in-category response rates, right? Across all organ systems, they did very, very well. So the drug will be used as monotherapy in third line. It may be used in fourth line. It may be used earlier. We're looking to also combine it with standard of care so we can move it earlier in the paradigm. But it should get used throughout the continuum.
Anything that works? Great. Thank you.
Yes.
We have an email question here. Michael, are there a bolus of patients from previous Revuforj trials, like expanded access or current clinical trial patients that may be transitioning to commercial therapy?
Right. So we do have an EAP for the drug. So patients are certainly participating that way. I wouldn't expect a bolus. I think these are very ill patients for the most part, and while they're doing well on therapy, potentially some will migrate over, but ultimately, it's not a huge bolus of patients. I think that may be a little bit different for Niktimvo, where patients are either on EAP or on other therapies, but probably have been on a little bit longer than the drug is actually working, and they might be waiting for the next therapy. The nature of the disease is a little bit different. So I wouldn't expect a bolus for Revuforj.
Maybe another one from me.
Just one in the audience.
Oh, oh, yeah. Go ahead. Yeah.
How will commercialization outside of the US?
Sorry, one more time?
Commercialization outside of the U.S.?
Yes. Yeah. The plan is we are assessing the opportunity for partners to participate with us. We're not going to commercialize on our own. So obviously, there's a lot of interest in what we're doing, and at the right time, we'll look for a partner to participate with us. Thank you.
Kind of post-ASH, there's been a lot of talk about sort of the competitive landscape in menin. Can you speak to why first-to-market matters in acute leukemias?
Yeah. Yeah. I mentioned it earlier. I think it is very important to be first. I think you have this experience that physicians build, right? They get comfortable. They get familiar with the drug, and it sets a very high bar for the next agent to be used. It has to be extremely differentiated from what we have. And frankly, we don't see that in any of the competitive molecules that have presented data to date. Most of them are far behind us, but even in terms of their data, we don't see anything that makes them anything more than sort of me-too products at this point.
So for us, we know that working closely with the physicians, delivering on getting drug into channel, getting drug to physicians, meeting them where they are, and making sure that we satisfy their patients, that is going to accrue dividends to us over time as we build this business. That is super important. And that can be whether we have a year, two years, three years, it all accrues to our benefit. So we're quite serious about that. I think that's a really important point.
Just maybe a quick one on Niktimvo. What are the final sort of gating factors to commercializing, getting to market in early Q2?
Right. We said the next few weeks. Yeah. So it's waiting on those vial sizes. The FDA is going through their process and making sure that those are in the label. That's the only hold-up.
Any final questions from the audience? All right. Thank you, Michael.
Yeah. Thank you, everyone. Appreciate it.