My name's Peter Lawson. I'm one of the biotech analysts at Barclays. I've had the pleasure of covering Syndax since I've been at Barclays and a little bit beyond that as well, or before that. I'm really pleased to have you on stage with me, Michael Metzger, CEO, and Steve Closter, Chief Commercial Officer. I'll be moderating this conversation. The first set of questions I've been asking, just to see if there's any kind of impact of the current administration, say, on supply chain, tariffs. Is there any worries there from import/export? Is there any worries from, I guess you've got prepared from COVID, but just any concerns we should be thinking about, APIs, et cetera?
Yeah, good question. First of all, let me just say thank you for having me in sunny Florida and be speaking with you. Obviously, your coverage is very good and fantastic and has been for a long time. Thank you for all that you're doing for us.
Thank you.
Just to answer your question, I think it's a timely question relative to tariffs and changes and so forth. No, I think we're pretty well situated today. I think in terms of we're now a commercial stage company. We have products that we're marketing in the U.S. I think we make our products in the U.S., and we're in a pretty good position relative to what we know today. I don't think there's anything in particular that we can point to that is particularly troubling that is going on with the administration that would impact us to the extent we know.
Thank you. Have you seen any kind of changes in communication with the FDA?
You know, we haven't. We've had a great relationship with the FDA. We just went through the NDA process and the BLA process, for that matter, last year with revumenib and axatilimab. Both went well. Drugs are both approved, which is a good place to be. So we have experience with them and have a good relationship with them. I think the changes that are being talked about, at least since most recently, I think some of those changes have been kind of rolled back, potential changes. In terms of one thing to keep in mind, we do pay PDUFA fees. User fees actually help to employ FDA people and allow us to have ongoing review work done.
We have an sNDA that we'll be filing this second quarter and hope to get the drug approved in a second indication, revumenib, by the end of the year. I think that we expect to be able to keep to our timelines. We haven't seen any impact relative to what at least we know today from FDA.
Gotcha. Thank you. I know it's a long-term impact, but NIH budgetary cuts, does that have any role or effects with clinical trial sites?
Again, I think it could, potentially could, but we haven't seen any impact just yet. I think we're kind of status quo.
Status quo.
Yeah. I think we're moving ahead. We are standing up a number of trials and doing a lot of work globally with our clinical trial sites. I think that plan is intact as far as we know. Any kind of cuts have not had a direct impact on that.
Gotcha. Thank you. How should we think about revenue launch and kind of the puts and takes for 2025? Coming back to.
Right. We did launch our two products. It is just an exciting time for the company as we are now a fully integrated commercial company. Maybe I will—we did report our first stub quarter. In the fourth quarter earnings, we talked about revenue for revumenib, not yet for axatilimab. Maybe I will give Steve the floor and let him kind of give some details. Yeah.
Yeah, yeah, happy to. As Michael said, we reported earnings, I think it was last Monday. We had $7.7 million in net sales through December. About a third of that was inventory. Ultimately, it would be about two weeks in the channel moving forward from inventory. Most of the sales, well, the other two-thirds were demand. Very few patients rolled off of EAP. How I would characterize the launch, and we had provided some commentary on our earnings call last Monday around a few things. It is finding patients and activating the user base. It is also getting the drug on formulary, managed care payer plans, and also getting patients on drug quickly. We have been able to—a very good start. This is data really through February. We call on about 2,000 treatment centers. We prioritize the top 200 centers. These are largely medium, large-sized academic institutions.
About a third of those institutions have written, which we think is a great start. The majority of those accounts have written more than once, which we believe is a really good start. Certainly, a lot more upside as we roll forward. On the managed care front, we have activated against payers well before the approval. Our formulary coverage is at 53% and growing every day. We think that is great at the third-month mark. More importantly, though, claims are being adjudicated and paid by payers, and claims are rolling through managed care formularies, Medicare Part D plans, commercial, as well as Medicaid. I think the last piece that is relevant is how do we get patients on drug quickly? We know the earlier diagnosis, getting patients on drug fast leads to really better outcomes. We have some great trade partners and some really talented internal folks.
Many patients are getting on drug within a couple of days. From what we see at the launch, it's good. We'll provide more data and more updates and perspective as we roll over the coming months. We've got our next earnings coming up in early May.
Yeah. I think just to cap it off, I think that we're in such a good position as a company to really dominate this space. We're the only menin inhibitor to have a KMT2A broad label. We probably will, for several years, be in that position. I think that market, in particular, has really good setup for us to bring a very important medicine to patients and really drive utilization. The idea is that we would get the second indication in 2025, first, hopefully, with guidelines in place and ultimately through the second sNDA, the sNDA process. I think we're in a really good position to really dominate the menin space over the next several years. Ultimately, we'll transition to moving more towards the front line.
Gotcha. How important is the first-to-market movement?
Super important. I mean, I think our point of view is, and I think this has been proven over time with oncology drugs, I think being first with a potential best-in-class agent is a game changer for physicians, right, in terms of getting the right organization lined up to meet the needs of physicians and patients immediately, as Steve described. We are doing right out of the gate. Having that relationship with the physician, giving them the service on an ongoing basis, making sure that they understand how to use the drug, and ultimately getting it paid for and following their patients, helping them to manage through the utilization of the drug. I think all of that is the type of service that you need to provide, but we can do it as first mover without any competition in the market.
It helps us really build competitive immunity for what we think will be several years.
Gotcha. Thank you. How should we think about the new patients coming on? Is that kind of a steady process? Is there seasonality there? Do you get a kind of initial bolus and just talk us through your thoughts?
Yeah, good question. We're not going to provide strict numbers yet. We need more data to see how things play out. I think when you think about the initial patients that come on drug, I mentioned there was not a whole lot of EAP patients, and there's not a lot of warehousing or bolus. Patients are just too sick, too advanced in their disease. What we saw, and some of this is anecdotal, we do not have all the data on specific patients, but you had patients that were close to first relapse, and you had patients that were brought off hospice. We believe, from what physicians tell us, physicians will move patients earlier. There are better treatment outcomes if you identify those patients earlier. That will certainly change over time. I mentioned the one-third of our priority accounts that have written. The rest will write.
I mean, there's urgent unmet need in the space. Physicians really like what they see in the profile of revumenib. It's not a matter of if those treatment centers and those associated physicians will prescribe. It's just a matter of when. We've got a very experienced customer engagement sales team. We've got support in the field to make sure that physicians and associated nursing staff understand how to use the drug successfully and onboard patients. We think it will be steady over the course of the year. We just need more time to activate the user base.
Gotcha. Okay. What should we think about growth in inventory for a couple of weeks or something like that? Is that a sensible number to think about? Should we think about any more patients coming off of the expanded access program?
There are no more patients off of our Expanded Access Program or EAP. They've already been transitioned for KMT2A patients. The inventory assumption is it'll be about two weeks, and that's typical for targeted therapies like this. The inventory that we built through December, the only change is inventory expansion as we move from quarter to quarter. Obviously, as demand grows, that inventory will build up, and we'll try to give some guidance on that over time.
Gotcha. You talked about these tier one and tier two accounts and what I think 33% penetrated. How quickly can you penetrate the rest? What's the most addressable kind of population we should think about as regards to those tier one and tier two sites?
Yeah, as I mentioned, I mean, it's not a matter of if they'll ultimately convert, it's when. They'll all go at their own pace. I mean, we're doing obviously everything we can. We've got great relationships with institutions. I think what's interesting in the user base right now, there's no clear pattern, meaning there are treatment centers that were involved in the clinical trials for revumenib, those that were not, and they're writing. I think that the base of prescribers and beyond the tier one, tier two users, there's a much larger group, right, that are, we'll call them Tier 3, meaning they're smaller. Smaller academic centers have begun to prescribe. I think also interestingly in this launch, community oncology tends to play a more substantive role later, year one, year two, year three.
There's not a ton of business in community oncology right now, but there's more than one would suspect. I think that speaks to their ability to identify patients through diagnostic testing. I think it also speaks to how they view the profile and the ability to use the drug and use it successfully.
Gotcha. Is there, as we think about those Tier 1 and Tier 2 accounts, is there kind of a goal by the quarter- by- quarter, or is that a kind of a fluctuating thing?
A goal that we have for converting? Sure. I mean, we'll look at our deployment activity levels. We prioritize those accounts because they have more patients available to be treated. The tier one, tier two account for about two-thirds the opportunity. We will be excited to share progress over time. Of course, we have some internal goals on what we want to accomplish. It's not ready to share those out externally.
Quarter- by- quarter, what metrics will you be sharing with the street?
Certainly the ones we've already covered, users, a sense of obviously repeat prescribers, managed care formulary coverage. In fact, I mean, the numbers I already provided here through February are outdated because they have gone up. We will look towards providing more substantive numbers over time. I think for us, it's still early, three months in. While we do have a limited distribution network, we don't have visibility to all of the data, meaning prescriptions that go through the specialty distributor side. We just know the customer the product goes to, but we don't know the number of patients. We don't know if it was a new patient or a refill or mutational status. For the specialty pharmacy side, which is about half of our business, we get more information.
As that coalesces over time, we get more usage, we'll be able to be more accurate, and then we'll be able to report more.
Gotcha. Has there been anything that surprised you in the launch in the first few weeks?
Yeah, some of the things I've already mentioned. I think the role of community oncology is certainly interesting, the makeup of who's been using. I mean, that we likely could have predicted. The base is where we expected, perhaps even on the bigger side. Traction on the drug is high. I think the setup, Michael may have referenced this a bit earlier, but just the setup for the data. We had NPM1 top-line data back in November. Two weeks later was the approval, and then ASH. I think all the interests in the menin space accrues to the benefit of revumenib because it's the only drug on the market. I think that's uniquely created some momentum for us as we roll through the early launch period. Yeah.
is not that it is a surprise, but I think the broad excitement about the profile and the ability to use the drug and use it well on a continual basis is really exciting the base. I think it is not a surprise, but it is nice to see.
Yeah, encouraging. As we think about the NPM1 side of the story, kind of the inclusion in the guidelines, do you think that kind of helps bolster sales, or do you expect a change there in the pace?
Yeah, no, I think, look, I think guidelines, what we had said is we'll look to publish the data in the second quarter, get it into the guidelines soon thereafter, hopefully around mid-year. The drug will hopefully get approved before the end of the year. There is a little gap in time. The ability to get guidelines, physicians' practice to guidelines, and I think that's a very important aspect of the launch. Yes, I think getting through guidelines and ultimately approval, I think that will be additive to what we're seeing in KMT2A. I mean, Steve mentioned script basis primarily KMT2A. We are seeing some additional, or at least hearing about some additional off-label use. We do not promote it that way, but that's certainly how physicians have the opportunity to use the drug in other capacities.
I think ultimately when you see guideline inclusion and an approval, that should really lead to the next leg of our growth, for sure.
Gotcha. Okay. Have you been seeing it used off-label, so in the NPM1 patients?
We've heard, yes, we have heard that. It's hard to identify in the data today, but we know that that's happening, yes.
Will you be able to break that out going forward, so NPM1 versus KMT2A?
Yeah, you want to comment on that?
Yeah, I mean, as I mentioned, some of the data we get through our specialty pharmacy and our hub, which is about half our business, we do not get all mutational status, severity of patient. We get some basic information. It is going to take us a little bit of time to piece this together. As more patients are put on drug and there is more experience from an HCP standpoint, we will be able to do more work and some claims work and some actual market research, really understand where. As Michael said, it is anecdotal, but we hear it from multiple sources.
Gotcha. Okay. Will that improve over time? Or do you care at the end of the day, or is that an important metric internally?
No, not necessarily. I mean, I think we know that the growth, we have tremendous opportunity in KMT2A, and we need to really work through that and just drive growth that way. We think that can really build the business, a substantial business. Ultimately, NPM1 will come when it does, and physicians are going to utilize it, and we think that's a big piece of business as well. They are kind of unrelated in a way because we think that they are both big drivers of upside. It does not necessarily mean that we have to break it out and have to show it, but we will do our best to actually track it at some level, yeah.
Good. Because initially, you want to track to just make sure there's nothing going wrong with it not being used in NPM1 patients.
Oh, sure, sure. No, I think we'll have a better feel for it. It's just in terms of importance, I think there's, to your point, there's some importance of understanding how the market's evolving and how we're penetrating. Ultimately, we think it's going to flow very well.
Gotcha. Do you have kind of internal goals of where you think that would be for like 2025, the distribution of NPM1 versus?
We do. I think it's premature to share anything like that. We know that the NPM1 market is, in terms of number of patients in relapse refractory, at least is bigger than KMT2A, but we haven't shared what we think the breakdown is and how much in terms of penetration over what time.
Gotcha. Just onto some of the clinical trial readouts and initiation. The venetoclax and unfit, so the HOVON study.
Yep.
Kind of remind us where you are in initiating and kind of the gating steps for the first patients.
Right. We are in the initiation phase of that trial. This is, as you mentioned, our venetoclax combo with revumenib frontline newly diagnosed patients. It is a global registration trial. We will be the first to frontline through this as the startup of this trial, highest unmet need. Really important new opportunity for us to be first to market. This trial is initiating now, and we are getting sites up and running. First patient, we have not said exactly when, but certainly in the second quarter, we will have that.
Gotcha. Okay. Initiated second quarter, you get the first patient.
Yeah.
Okay. What is the split you think is going to be U.S. versus ex- U.S. for that trial?
I'd say predominantly it's a, I would say ex- U.S. I mean, we have U.S. sites as well, but a lot of our sites will stand up outside the U.S. It's a global trial, and we'll look to get it drug registered globally.
Gotcha. Just going back to kind of the funding questions, I guess, is there any worry, European funding or external funding?
No, no, I don't think so.
Any worries around the ability to control that study just because it's a HOVON-run study?
We have a very close collaboration with HOVON, so it's collaborative in that sense. We have a lot of involvement in that, both in the standup of trials and how we do that. They are the sponsor, but we are working actively in the U.S. and outside the U.S. with them to do that. It is a very close relationship. They are expert in this. They are probably the best in the world at executing on these trials. They have done it many times. They have the premier centers, premier physicians involved. They have things like centralized patient identification, all the things that you would want. They are a very proactive group. I think we feel very confident that they will be excellent to work with and have been so far.
Okay. Are there any, what are the kind of the pros and cons of working with HOVON? Clearly, you've highlighted some of the benefits of they're up and running and they kind of know what they're doing. Any time delays in getting the data or just?
No, quite the contrary. I think they're excellent at they have a centralized system for collecting data, and they're very good at and experienced at doing that. I mean, we're closely collaborating with them, so there's no issue with timing of data transfer or any of that sharing. No, I don't think there's any downside. I think we actually see all the upside of working with them. I mean, the alternative, of course, is to do it solely on our own and stand up a global trial. We'll do that also, right? We're doing that in the fit population as we start to get those trials up and running in 2025. We're taking an approach where it's not just one size fits all.
We're doing different trials and working with different people to get the best of the working environment, people that have a lot of experience doing these things.
Gotcha. Thank you. Should we say, is there an interim read that we should be thinking about for the HOVON study?
We haven't been completely transparent with all of our plans. I think we've announced the trial design. It's on CT.gov, so you can see it, but it's a randomized trial with an OS endpoint that is the gold standard as we know. An interim CR endpoint is something that I think others have talked about as an accelerated approval endpoint and something that we haven't expressly said out publicly, but I think it's a potential option for us as well. Any kind of accelerated endpoint, I think we should assume, whether it's in the HOVON trial and some of our fit trials that we'll be working through and getting up and running this year, I think you should assume that we'll avail ourselves of any accelerated approval endpoint that is available, right? We have conversations with regulators.
We don't usually talk about our regulatory interactions, but I think we feel quite confident that we'll be in a good position to leverage some of these endpoints as well.
Now, is that a seamless process where you can kind of make those amendments to have an accelerated endpoint integrated into the trial?
Yes.
Perfect. Nice and clear. Thank you. Just expectations around CR rates and OS that we should be thinking about for the control arm, at least.
For the HOVON trial?
Yes.
Yeah. I mean, again, we haven't released the statistics. I think you can think about the VIALE-A trial as a kind of model for some of this. I think in that trial, the CR rate was 43%. If I remember, OS was 14.7 months. I think those are the hurdles for the VIALE-A trial. Again, we haven't talked about what we would need to achieve relative to an increment on top of what standard of care is, but I think you should kind of think about those metrics as at least the baseline of what we need to do better than.
Yeah. Should we use BEAT AML as a kind of a proxy for what's being run now?
Same population. We'll take a broad population. BEAT AML enrolled and is enrolling both NPM1 and KMT2A patients. That'll be also the case in our trial. The trial will be really powered for NPM1. That's the majority. It's a much bigger patient population, especially in the unfit population than KMT2A is, because most of the KMT2A patients are younger and fit for chemo. I think that is the population that has been enrolling in BEAT AML. It's very much similar. I would certainly think about that as a proxy for what we might be able to accomplish in our trial, right? That's why we're so encouraged. That's why the physicians are so encouraged, seeing in the BEAT AML trial, 100% response rate, 95% MRD negativity, just fantastic data on top of venetoclax. That's what we're gearing up for.
Okay. As we think about first-line fit trials, it sounds like there are other trials being planned and worked through. Kind of what should we expect in the second half as regards to those fit trials?
Right. We're excited about our plans there. We haven't been as explicit on the fit trials yet. We will be finishing our phase one dose ranging. We already feel pretty confident in the dose. We're exploring two doses that are both active as monotherapy. We've also explored those doses in a chemo combo in our AUGMENT-102 trial. We have a very good understanding of what the dose is likely to be. We're enrolling some additional patients there to just confirm that. We're, at the same time, looking to stand up, I'd say, more than a few trials this year. There are going to be some will be registration-directed, some will be more guideline-directed. There are several populations within the fit setting that we need to address.
Our strategy, which we'll keep private for the time being, really looks to address the broadest and most important populations there, get the drug approved, and also build a base of data that physicians can relate to as they start to use our drug as an approved agent.
We've hit the bottom of the hour, but thank you so much. Always a pleasure speaking to you.
Thank you. Nice to see you. Thank you.