Great. Thanks, everyone, for continuing to join us here at the Stifel two-day virtual oncology event. I keep hearing that word up. My name is Brad Canino, Senior Analyst here. Very happy to do the next fireside chat with Syndax. We've got Michael Metzger, CEO, and Steve Kloster, Chief Commercial Officer. Thanks so much for joining us today. Yeah, Brad, thank you. It's great to be here. We're doing it old school on the video today, but excited to talk about the company and chat with you a bit. I like it. Let's just start off. Could you do an intro to Syndax, state of the business, and you've transitioned to a commercial stage biotech in the past few quarters? Give us the intro. Yeah, look, I think exciting time for the company as Syndax has really grown up and grown into not only a company that can develop drugs, but one that is commercializing them as well. We have two agents that were approved last year, and one is Niktimvo for chronic graft-versus-host disease, and the other, of course, is Revuforj, which is for acute leukemia, ALL, AML, KMT2A, adult and pediatric leukemia. Both new agents addressing really high unmet need, and we believe very important for patients. We are excited to get them into the hands of physicians and patients so they can start out treating these diseases. The company has done so far very well. I think on our last earnings call, we talked about our early performance for Revuforj. Steve will obviously talk more about that today. We will have an upcoming earnings call talking about our sales performance in both agents now. Niktimvo is also launched. We are excited about that. I think we continue to develop both drugs aggressively in their respective indications. For Revuforj, we have an sNDA filing in the second quarter that we have guided to, and we expect to have that drug approved in the second indication before the end of the year, publish the data as well in the near term here, and then hopefully get into guidelines shortly. I think we have a building franchise. We are first to market in the menin space, and we feel like we have a tremendous advantage with the agent we have in hand and that we are there first and starting off out of the gates very well. For Niktimvo, we'll continue to develop that in earlier line settings and hope to advance in that way. We also have other indications that we're developing outside of GVHD for IPF. A lot of development, a lot of data coming over the next months, I would say, and hope to have another approval here in 2025 for Revuforj. Really exciting both from a sales and marketing perspective and launch perspective, but also from development too. Okay. Now, I have to be honest, I don't really know how to ask the first question uniquely or with any sort of informed perspective, but you're a commercial company. You're about to have another regulatory review underway. There's a lot of questions floating around about tariffs, FDA changes. How do you like to answer the question about how that is or is not impacting your business? Right. It's a little naive to say that it doesn't impact your business in any way because I think we don't know everything that's likely in front of us. I do feel like today, where we sit today relative to FDA, we have a very long-standing relationship with them. We work closely with them. We know the people there well. We hope they all retain their positions and continue to do the great work that they do. We have not been notified by the FDA of any change in timing or plan relative to our own submissions and work that we have ongoing. We're optimistic that our timelines will hold and continue that work as planned. I don't have anything in particular relative to our company or our filings that will be impacted by changes at FDA, and we continue to monitor that situation. In terms of tariffs, I think, again, that's also an evolving situation. We are, I think, advantaged in the sense that finished goods, packaged goods made in the US, we have intermediates, API, and so forth, almost entirely sourced here as well. We feel like the impact under any tariff regime will be of really very little consequence to us relative to Revuforj and Niktimvo. I think we feel like we're in a good place. Again, we monitor that situation. I guess the last would be intellectual property, domicile, where that's located. It's all onshore US-based IP, and so that's not an impact. We don't envision an impact there as well. Overall, I think for the things that you asked about, I think we're probably as well off as anybody in our space could be at this point. Again, situations change and we remain vigilant, but we think we're well positioned as of today. Okay. Back to things that you can control. What are you seeing in the first months of launch in terms of demand for Revuforj, revumenib? And what is the physician feedback as that first use occurs? Maybe I'll let Steve dive into this. I think he's the person to answer. Go ahead, Steve. Yeah, no, thanks for the question, Brad. Obviously, good to be here today. As Michael said, we're off to a good start. We're optimistic about what we're seeing. There's really three things that underpin the launch. First, I'd say there's the unmet need for KMT2A relapse refractory patients. It's clear the urgency to treat is incredibly high. The drug has a great label. Early feedback from physicians is they like the profile and they like what they're seeing it do for patients that they've been treating. It can do what it needs to from an efficacy standpoint. It's got a manageable safety and tolerability profile. The dosing is very clear. As we know, the label is wide, meaning it's approved for adults and peds as young as age one, AML, ALL, KMT2A. Ultimately, obviously, there'll be a filing for NPM1. All of that appeals to physicians. It's important that we get out of the gate strong. Our focus on the commercial side has just been flawless execution right out of the gates. We've got an experienced and a talented team activated against all customer types, really showing treatment centers on how to use the drug properly, working closely with payers to adjudicate paid claims, increasing formulary coverage, which increases every month, and getting patients on drug very, very quickly through our trade partners. As previously announced at our last earnings call, Q4 sales were strong at $7.7 million. About a third of that was in stocking. The remainder was demand. We have given updates over time on the number of accounts that have prescribed at least a generalization in our most important accounts. Through February, we had about a third of priority accounts. There's about 200 treatment centers, which we do prioritize just based on the patients that they treat. They've prescribed, many have prescribed more than once. Importantly, still plenty of upside to converting accounts, which we're confident that will do. As Michael said, we'll have an update at our May earnings call. That number now is already well above what you'd suspect. We do get asked questions on a bolus or warehousing of patients. Physicians, they were excited for the drug to come to market, but the disease is too advanced for any significant bolus. We did see a wide range of patient types prescribed from those on hospice all the way to those to first relapse. Over time, we'll expect more patients to be treated in that first relapse setting, which we think will offer a better prognosis for treatment. Physicians early on are able to get patients to respond to some to transplant. The expectation is that there'll be continued treatment beyond that if warranted. Good start and more positive news to share in the future on our progress. How has the initial real-world Revuforj safety profile played out? How are physicians handling the QTc monitoring and any dose adjustments that are required for that? Steve, go ahead. Yeah, happy to. You know, Brad, it's well tolerated. The safety profile is absolutely well characterized in the label. From what we've heard from physicians along with their staff, they're able to successfully initiate treatment with Revuforj and keep patients on for as long as needed and warranted. That's great and exactly what we expected. Patients do tend to be complex, and physicians are used to managing multiple meds and ones that, for instance, may have impact on QTc. The label's clear on what to do when starting treatment, including performing an ECG. That's fairly routine prior to treatment initiation. Thereafter, at intervals consistent with typical care that these very ill patients often receive, they monitor for it and manage it if needed. It's certainly not preventing physicians from using the drug successfully in any way. We're certainly encouraged by that, and that's what we expected to see. The good thing is usage broadens to more treaters, to more patients, and that's rapidly happening. We expect that this early experience to only get better over time. You mentioned a number of accounts and a penetration into top accounts. I think as we're trying to think about demand levers that could be pulled, are you seeing that these activated accounts already have multiple patients on therapy at one time? Is a lot of growth going to be from going out and reaching new accounts, or is there still depth at the individual accounts that you've already activated still accessible to help grow that sales pie as well? Steve, go ahead. Yep. Good question, Brad. I'd say it's going to come certainly from both. We're focused on depth and breadth, meaning we're activating accounts to prescribe for really the very first time, but also going deeper into those accounts that have additional patient opportunities. They all do, right? Some have more than others, which is why we focus on the priority accounts. We're gaining traction in both. The business is, of course, going to build due to those dynamics. I'd say this: based on our experience, getting that first patient on treatment is a big deal. It takes a little bit more time and effort to get that started. Then treating subsequent patients is easier, right? They've gone over those first hurdles. We've got a variety of customer-facing roles and support to ensure there's education in place and everything the physician, their staff, and patients need for treatment success. We absolutely take nothing for granted. Our goal is really to provide a superior experience for everyone involved. So far, physicians are giving us high marks. Okay. What are you seeing early innings in terms of duration of therapy? I guess one way to look at your last quarter is you got $5 million organic really in just one month. Are you expecting that to extrapolate to three months on therapy with additional patient adds? Help us think about how treatment durations can impact your sales results for this year. Yeah, absolutely. Too early, the first part of your question, too early to comment on duration of therapy. We do ultimately expect there will be patients who stay on for much longer periods of time. Some will go to transplant. Obviously, some will go back on treatment for a sustained period of time or maintenance. That will play over time and we'll monitor it. From what we can see in the specialty pharmacy channel and our hub, we're seeing exactly what we'd want to see in terms of refill rates from that first refill. We even have some patients that are embarking on their fourth. We've got some visibility on that group, that first cohort of patients in Q4. For some patients who discontinue, we've heard anecdotally that they're responding and some are, of course, going to transplant. More to come on this. We know that's a big question that folks have. We'll learn more over time and we'll share as we can. The second part of your question, in terms of the $5 million in demand from Q4, we're not going to comment yet on what we've seen specifically in Q1 as we've teed up. We'll provide a lot more color in that May earnings call in terms of what we've seen over the past three months. Steve, the component of stocking was about one-third, you said, from Q4. How should we think about that in 1Q? Should we think about it from an absolute dollar perspective, a relative kind of one-third staying consistent? How should you prepare us going into Q1 for that? Yeah, it's something that once the inventory stocked, the only change is really increases in stocking, and that's basically tied right to demand. As a result of our limited distribution channel, we would never expect to see more than two to three weeks in inventory in the channel. This is in line with other specialty products. We expect to see that in Q1 where we've ended. I don't suspect that'll change moving forward. It'll be two to three weeks in inventory at any one time. Ultimately, I just want to make sure that our specialty pharmacies and distributors have adequate supply to meet demand. We'll never get ahead of that stocking, meaning demand will likely track closely to what we see in the quarters. Now, how do other levers for growth come into play for this year, such as NPM1 off-label use initially and then moving to a formal approval potentially by the end of this year? Steve, you want to take that as well? Yeah, sure. Good question, Brad. I mean, it's a changing market, data coming out, new indications on the horizon. Obviously, we're never going to promote outside of our indication from a commercial perspective. We've certainly heard anecdotally physicians who are choosing to prescribe Revuforj for patients with NPM1 mutations and are getting the drug covered from what we understand by payers. We believe right now the large majority of prescriptions is KMT2A. We can see in the specialty pharmacy and hub data if the patient has been diagnosed with AML or ALL, but we can't see their mutational status. As we know, hematologists tend to be aggressive treaters because they have to be, right? It's particularly in cases where they have no options. They are comfortable prescribing off-label simply due to need and familiarity that they have with a product. That experience with Revuforj is going rapidly. There could be some impact with the publication of the pivotal NPM1 data. I think Michael referenced this. We expect that soon. There could be the intent is to have it listed in the NCCN guidelines for support that would follow soon after the publication and a formal indication, obviously, at the end of this year. All those will be levers to utilization. Okay. Michael, anything else you want to say about timing of publication, listing, approval? We did just get from Kura yesterday that the NDA was submitted for them for NPM1 on March 31. Yeah. I think our guidance has been publication, NPM1. It's actually quite important. I think we have the publication that we hope to have in the second quarter. We think we'll have NCCN listing pretty quickly thereafter. Also, a little out of our control, but hopefully that'll happen in the first half of this year as well. Submission and approval before the end of the year for NPM1. I think that's the general timing. We said we'll have the sNDA in the second quarter. That was our guidance. We haven't updated our guidance, but we're on track. This whole plan is, I think, a very nice complement to the launching KMT2A. Obviously, we're out there, and this is Steve detailed doing nicely. I think the physicians practice the guidelines. It's pretty important to get into the guidelines as soon as you can. As you have an approved drug, you have that advantage where if you publish the data, then you can get it into the guidelines. All of that really builds, we think will build utilization in the category and strengthen our franchise as we await approval towards the end of the year. I think a really actually a nice setup for us. Okay. You are also launching a second product with your partner Incyte, Niktimvo. Yeah. If the question is, how closely should we look at the precedent cGVHD launches to map out what is possible for that product this year? Yeah, it's a great idea. I think there's a very nice analog in the third line. Again, just to remind everybody, this is a third-line GVHD approval. This is two prior treatments before you would be receiving Niktimvo. Our closest competitor there is a product called Rezurock. That product is used in the third line. We believe that this is a new offering in Niktimvo, new mechanism of action. Physicians are, I think, really excited about it in the sense that it brings something new to the category and the opportunity to expand the category. That analog, that product is doing about $500 million in its third year of sales. Looks like it could do quite well from here. It's growing about 50%. I think we believe we could do just as well or better. We're priced at a premium to the category, as well as the fact that we know from our data in some very sick patients that this is a product that's not only well tolerated, but extremely efficacious. Physicians expect to give this product to patients and potentially keep them on for months, if not years. I think there's an opportunity to take the category and make it larger. We know physicians tend to take patients and cycle them through various therapies. We'll see patients that have received Rezurock and Jakafi first, and we'll see patients in advance of Rezurock as well. I think there's really a unique opportunity, and I think people maybe don't fully understand that category as well as maybe they will in a few years after we're done expanding it. I think it's a really great opportunity for a new agent. That analog is, I think, something to definitely keep your eye on. Now, you roughly share economics with your partner Incyte. From your portion that you retain, you create a synthetic royalty deal from that to finance the company, which I think with current market conditions, we're going to look back and say that was a really good deal. Kudos to that. How would you now describe the value that Syndax still retains in Niktimvo, and why should investors pay attention and reward a strong launch for this product? Yeah, another great question, Brad. I think this is how I'd characterize a high-margin product. The margins are good. The promotion and the spending that we do against the product is appropriate, but it does leave quite a bit of room for us to continue to have a revenue stream beyond what we pay out to our partner in Royalty Pharma. That is a 13.8% synthetic royalty, as you pointed out, with a cap. At some point, once we pay back 2.35 times what they've given to us, which was $350 million, that cap will ultimately expire, or the royalty will. I think the upside longer term is certainly there with new indications and IPF pending. In the meantime, with a high-margin product, again, the product is priced at a premium to the category. I think we have the opportunity to do quite well with an ongoing royalty stream or an ongoing revenue stream. I think, again, this is a, we believe, going to be a quite substantial product, blockbuster-type product. With that kind of revenue potential and margin expansion, I think you have the opportunity to really participate meaningfully on a near-term basis. Okay. Now moving on to the additional studies being conducted with Revuforj, you have the frontline unfit AML patient study with Venclexta as a triplet being conducted with HOVON. Can you just discuss the status and expected timelines for that study? Yeah. Good news is we've started that trial. We're opening sites now, and sites are open and ready to enroll patients. We'll say more about that on our May call. I think we're excited about that trial. HOVON is a great partner for us. It's a global registration trial slated to enroll over 400 patients. It's the first one of its kind. We're the first to open up that trial in the unfit population on top of Venclexta. Exciting development for us and certainly the category. This will take time to enroll. We haven't given very clear guidance as to when that will be completed. It will take some time, several months to get that fully enrolled. Many, many sites all over the world will be conducting that for us. What regulatory endpoints and pathways do you think are available for US FDA approval of that combination in the frontline unfit setting? Right. Traditionally, we've talked about the fact that overall survival is the gold standard there, and that's the way the trial is designed. The question is, are there some accelerated approval opportunities? We believe there may be. We haven't talked about our regulatory interactions there, but I think we're certainly confident that if those opportunities for accelerated approval are available, they'll be available to us as well as other sponsors. I think we've looked at CR as an MRD-negative CR being an opportunity for accelerated approval. That would be one. I think there's some precedent there in that population to incorporate that into trials as well. That is one potential that we're keeping an open mind towards. What is the status of the other combination with 7+3 chemotherapy for the patients who are fitter in frontline AML? Why has that been less of a priority relative to the Venclexta combo at Syndax? I wouldn't call it a lesser priority. I would just say the highest unmet need in frontline is the unfit patient population. I think you can get the results more quickly based on the fact that overall survival is shorter than you have in the fit population. It's not a lesser priority. We were the first to generate data in that category, again, addressing the high unmet need. That has moved along at a slightly different pace. I would say in the fit population, we are on pace to start trials this year, addressing that. We'll have our phase one data confirming dose. We'll have that data in the second half of this year. We expect to start trials right away and have a robust program. It's not just one population of patients, as you know, in the fit setting. Whether it's NPM1, KMT2A, mutant populations, you have to look at it holistically. We'll have registration trials to address some of these populations that we believe are most important, and others will take more of a guideline approach to generate data more quickly. I think we'll be very meaningfully represented in these different populations. We will look to get started. First, we'll see data in the second half, but we'll, at the same time, stand up these trials to kick off later in the year. Okay. Last for me then, you mentioned the second half data, phase I, 7+3 combo. What would be a good outcome for that first data that you disclose? Right. Just think about it historically. The response rates to 7+3 are expected to be around 60% for patients with KMT2A, closer to 85% for patients with NPM1 mutations. We've seen data in addition to other meta-inhibitors that can improve on these responses. We'd expect to see something similar when you add Revuforj to this regimen. We also hope to improve on the MRD rates as well as the duration of response with the triplet. For KMT2A, we'd also look to see an increase in the proportion of patients that are able to proceed to transplant, for instance, right? That's an important point. Also, which percentage of patients or how many patients can receive Revuforj in the maintenance capacity. I think there's some benchmarks, if you will. We hope to show some of that data until we're moving in the right direction, at least in the early trials, which we will have in the second half. Okay. Great. Unfortunately, we're out of time. Michael, Steve Kloster, thank you so much for joining us at the event. We really appreciate it. Thank you, everyone, for joining and listening in. Great, Brad. Thank you so much. Appreciate it so much. Thanks, Brad. Great day.