Syndax at Stifel Forum: Strategic Drug Launches

On Wednesday, April 9, 2025, Syndax Pharmaceuticals (NASDAQ: SNDX) participated in the Stifel 2025 Virtual Targeted Oncology Forum. The company highlighted its strategic initiatives, focusing on the commercialization of newly approved drugs Nectimvo and REVUFORGE. While expressing optimism about early demand and positive physician feedback, they also acknowledged potential challenges from regulatory changes and tariffs.

Key Takeaways

• Syndax is optimistic about the launch trajectory of REVUFORGE and Nectimvo.
• Strong early demand for REVUFORGE, especially for KMT2A relapsed/refractory patients.
• Nectimvo is positioned as a third-line treatment for chronic graft-versus-host disease (cGVHD).
• The company plans to expand REVUFORGE's label to include NPM1 mutations.
• Syndax is actively pursuing combination studies to enhance treatment options.

Financial Results

• Q4 2023 Sales for REVUFORGE totaled $7.7 million.

- Demand component: Approximately $5 million

- Stocking component: Approximately $2.7 million

• Nectimvo is expected to generate high margins, benefiting from a synthetic royalty deal with Royalty Pharma.

Operational Updates

• REVUFORGE Launch:

- Strong early demand due to unmet needs for KMT2A patients.

- Focus on treatment center activation and payer engagement.

- One-third of priority accounts have prescribed REVUFORGE by February.

• Nectimvo Launch:

- Launched as a third-line cGVHD treatment in partnership with Insight.

- Aims to expand the cGVHD market with a new mechanism of action.

• Clinical Development:

- sNDA filing for REVUFORGE's NPM1 mutation expected in Q2, with potential approval by year-end.

- Initiated frontline unfit AML study with venetoclax and azacitidine.

- Phase 1 data for REVUFORGE with 7+3 chemotherapy expected in the second half of the year.

Future Outlook

• REVUFORGE:

- Awaiting publication of NPM1 data and potential approval by the end of the year.

- Combination studies with Ven/Aza and 7+3 expected to drive growth.

• Nectimvo:

- Exploring new indications, including IPF, to expand revenue streams.

Q&A Highlights

• FDA Changes and Tariffs:

- No immediate impact expected due to US-centric manufacturing and FDA relationships.

• Duration of Therapy (REVUFORGE):

- Positive refill rates observed, but specific guidance on therapy duration is too early.

• NPM1 Off-Label Use:

- Anecdotal reports of off-label use for NPM1 mutations, with formal indication expected to increase utilization.

• Combination Studies:

- Frontline unfit AML study with Ven/Aza is underway, with potential for accelerated approval based on specific endpoints.

In conclusion, Syndax remains committed to advancing its drug portfolio and addressing unmet medical needs. For further details, readers are encouraged to refer to the full transcript below.

Full transcript - Stifel 2025 Virtual Targeted Oncology Forum:

Brett Canino, Senior Analyst, Stifel: K. Great. Thanks everyone for continuing to join us here at the Stifel two day virtual oncology oncology event. I keep bringing that word up. My name is Brett 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.

Michael Metzger, CEO, Syndax: Yeah, Brad. Thank you. It's, great to be here. We're doing it old school on the, on the video today, but, excited to talk about the company and chat with you a

Brett Canino, Senior Analyst, Stifel: bit. I like it. So 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.

Michael Metzger, CEO, Syndax: 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. So we have two agents that were approved last year, and one is Nectimvo for chronic graft versus host disease, and the other, of course, is REVUFORGE, which is for acute leukemia ALL, AML, KMT2A adult and pediatric leukemia. So both new agents addressing really high unmet need, and we believe very important for patients. So we're 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 RevuForge. Steve will obviously talk more about that today. And we'll have an upcoming earnings call talking about our sales performance in both agents now. Niktymbo has also launched.

And so we're excited about that. I think we continue to develop both drugs aggressively, in their respective indications. For REVUFORGE, we have an sNDA filing in the second quarter that we've 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. And so I think we have a building franchise. We're first to market, in the menin space, and we feel like we have a tremendous advantage with the agent we have in hand that we're, there first and and, starting starting off out of the gates very well.

And then for Nick Timbo, we'll continue to, develop that in earlier line settings, and and hope to, advance in that way. Also have, other indications that we're developing outside of GVHD for IPF. So a lot of development, a lot of data coming, over the next, months, I would say, and, you know, hope to have another approval here in 2025 for RevuForge. So really exciting, both from a sales and marketing perspective and launch perspective, but also from development too.

Brett Canino, Senior Analyst, Stifel: 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?

Michael Metzger, CEO, Syndax: Right. So I it's a little naive to say that it doesn't impact your business in any way because, I think we we we we don't know everything that's, likely in front of us. But 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, you know, submissions and work that we have ongoing. So we're optimistic that our timelines will hold and continue that work as planned. So, again, 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. And then in terms of tariffs, I think, again, that's also an evolving situation.

We are, I think, advantaged in the in the sense that, you know, finished goods, packaged goods, made in The US, you know, have intermediates, API, and so forth, almost entirely, sourced here as well. And, you know, we feel like the impact under any tariff regime will be of, really very little consequence to us relative to Reviforge and and, Nick Timbo. So I think we feel like we're in a we're in a good place. But, we monitor that situation. And I guess the the last would be, you know, intellectual property, domicile where where that, 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. So overall, I think, for the things that you asked about, I think we're probably as well off as as anybody in our space could be at this point. Again, situations change, and we we remain vigilant. But we we we think we're well positioned as of today.

Brett Canino, Senior Analyst, Stifel: Okay. Well, back to things that you can control. What are you seeing in the first month of launch in terms of demand for RevuForge, RevuMed? And what is the physician's feedback as that first use occurs?

Michael Metzger, CEO, Syndax: So maybe I'll let Steve dive into this. I think he's the he's the person to answer. Go ahead, Steve.

Steve Kloster, Chief Commercial Officer, Syndax: Yeah. No. Thanks for the the question, Brad, and and obviously good to be here today. So, you know, as Michael said, we're off to a good start. We're optimistic about what we're seeing.

And there's really three things that underpin the launch. You know, first, I'd say there's, the unmet need for KAT two AR relapsed refractory patients. It's clear. The urgency treat, is incredibly high. The drug has a great label, and early feedback from physicians is they like the profile and they like what they're seeing it do for for patients that they've been treating.

It can do what it needs to from an efficacy standpoint. You know, it's got a manageable safety and tolerability profile. The dosing is very clear. As we know, the the label is wide, meaning it's approved for adults and peds as young as age one, AML, ALL, KNT2AR ultimately, obviously, there'll be a filing for MPM1. And all of that appeals to physicians.

You know, it's important that we get out of the gate strong. So 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, you know, q four sales were strong, at 7,700,000.0. 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. So, 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 that they treat. They've prescribed many have prescribed more than once, but importantly, still plenty of upside to converting accounts, which we're confident, that we'll do.

And as Michael said, we'll have an update at our our May earnings call. And that number now is already well above what you'd suspect. We do get asked questions on a on a bolus or warehousing of patients. And and physicians, they were excited for the drug to come to market, but, the disease is too advanced for any significant bolus. But 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 better prognosis for treatment. You know, and physicians early on are able to get patients to response, some to transplant, And, and the expectation is that there'll be continued treatment beyond that if warranted. So good start, and more positive news to share in the future on our progress.

Brett Canino, Senior Analyst, Stifel: How has the initial real world ReadyForge safety And and how are physicians handling the QTC monitoring and any dose adjustments that are required for that?

Michael Metzger, CEO, Syndax: Steve, go ahead.

Steve Kloster, Chief Commercial Officer, Syndax: Yeah. Happy to. You know, Brad, it's it's well tolerated, and the safety profile is is absolutely well characterized in the label. And from what we've heard from physicians along with their staff, they're able to successfully initiate treatment with RevuForge and keep patients on for as long as needed and warranted. So, that's great and exactly, you know, what we expected.

Patients do tend to be complex, you know, and physicians are used to managing multiple meds and ones that, for instance, may have impact on QTC. So the label's clear on what to do when starting treatment, including performing an ECG. That's fairly routine prior to a treatment initiation, and thereafter, it intervals consistent with typical care that these very ill patients often receive and and monitor for it and manage it if needed. So it's it's certainly not preventing physicians from using the drug successfully in any way. So we're certainly encouraged by that, and that's what we expected to see.

And, you know, 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.

Brett Canino, Senior Analyst, Stifel: And 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? And is a lot of growth going to be from going out and reaching new accounts? Or is there still depth that the individual accounts that you've already activated still accessible to help grow that sales pie as well?

Michael Metzger, CEO, Syndax: Steve, go ahead.

Steve Kloster, Chief Commercial Officer, Syndax: Yep. So, good question. You know, Brad and and, I'd say it's gonna come certainly from both. You know, 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. But we're getting traction in both. You know? And the business is, of course, gonna build due to those dynamics.

You know? I'd say this based on our experience, getting that first patient on treatment is a big deal. You know? It takes a little bit more time and effort, to get that started, and then treating subsequent patients is is easier. Right?

They've gone over those first hurdles. So we've got a variety of customer facing roles and support to ensure there's education in place and and everything the physician, their staff, and patients need for treatment success. We absolutely take nothing for granted. You know, our goal is is really to provide a superior experience for everyone involved, And so far, physicians are giving us high marks.

Brett Canino, Senior Analyst, Stifel: Okay. And 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 5,000,000 organic really in just one month. So 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.

Yes. Yeah.

Steve Kloster, Chief Commercial Officer, Syndax: Absolutely. So, you know, too earlier, the first part of your question, too early to comment on duration of therapy. You know, 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 sustained period of time or maintenance.

And that will play over time and we'll monitor it. You know, from what we can see in, the specialty pharmacy channel, and our hub, we're seeing exactly what we'd wanna see in terms of refill rates from that first refill. We even have some patients that are that are embarking on their fourth. So we've got some visibility, on that group, that that first cohort of patients in q four. And for some patients who discontinue, we've heard anecdotally that that they're responding and and some are of course going to transplant.

So 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, you know, in terms of the $5,000,000 in demand from q four, you know, we're not gonna comment yet on what we've seen specifically in q one as as we've teed up. We'll we'll provide a lot more color in that May earnings call, in terms of what what we've seen over the past three months.

Brett Canino, Senior Analyst, Stifel: And and, Steve, the component of of stocking, you know, it was about one thirty you said from 4Q. 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? What should how should you prepare us going into 1Q for that?

Steve Kloster, Chief Commercial Officer, Syndax: Yeah. It's, something that, you know, once the inventory stocked it, you know, the only change is really increases in in stocking, and that's that's basically tied right to demand. So, you know, as a result of our limited distribution channel, you know, 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 q one, where we've ended.

And I I would I don't suspect that'll change moving forward. It'll it'll be two to three weeks in inventory at any one time. And and I'll ultimately, I just wanna make sure that our specialty pharmacies and distributors have adequate supply to meet demand, but we'll never get ahead of, of that of that stock, meaning demand will likely, close you know, track closely to to what we see in the quarters.

Brett Canino, Senior Analyst, Stifel: K. Now how do other levers for growth come into play for this year, such as NPM one off label use initially and then moving to a formal approval potentially by the end of this year?

Michael Metzger, CEO, Syndax: Steve, you want to take that as well?

Steve Kloster, Chief Commercial Officer, Syndax: Yeah. Sure. Well, 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 Revuforge for patients with, MPM one mutations and are and are getting the drug covered from what we understand by payers. But, we, you know, we believe right now that large majority prescriptions is KAT two AR. We can see in the specialty pharmacy and hub date if the patient has been diagnosed with AML or ALL, but we can't see their their mutational status. As we know, hematologists tend to be aggressive treaters because they have to be. Right?

Particularly cases where they have no option. So they are comfortable prescribing off label simply due to need and familiarity that they have with the product, and that experience with the RevuForge is is going rapidly. There could be some impact with the publication of pivotal n p m one 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. And and all those will be levers to utilization.

Brett Canino, Senior Analyst, Stifel: K. Michael, anything else you want to say about timing of publication listing approval? We did just get from Cura yesterday that the NDA was submitted for them for NPM1 on March 31.

Michael Metzger, CEO, Syndax: Yes. So 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 will happen in the first half of this year as well.

And approval submission and approval before the end of the year for MPM1. So 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. And this whole plan is, I think, a very nice complement to the launching KMT-2A. So obviously, we're out there, and this is Steve Detail doing nicely. I think the physicians practice the guidelines, so it's pretty important to get into the guidelines as soon as you can. As have an approved drug, you have that advantage where if you publish the data, then you can get it into the guidelines.

So 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. So I think a really actually a nice setup for us.

Brett Canino, Senior Analyst, Stifel: Yeah. And you're also launching a second product with your partner Insight, Nick Timbo. Yeah. If the question is, how closely did we look at the precedent eGVHD launches to map out what is possible for that product this year?

Michael Metzger, CEO, Syndax: 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. So this is your two prior treatments before you would be receiving Nictimvo.

Our closest competitor there is a product called Bresoroc. That product is used in the third line. We believe that this is a, you know, new offering in Nictimbo, new mechanism of action. Physicians are, you know, I think, really excited about it in the sense that it brings, you know, something new to the category and the opportunity to expand the category. That analog that product is doing about 500 some odd million dollars in its third year of sales.

Looks like it, you know, could do quite well from here. It's growing about 50%. So I think, you know, 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 very sick patients that this is a product that's not only well tolerated but extremely efficacious. And physicians expect to give this product to patients and potentially keep them on for months, if not years.

So 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. So we'll see patients that have received Reserock and Jakafi first, and we'll see patients in advance of Reserock as well. And so 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 a few years after we're done expanding it. But I think, I think it's a really great opportunity for a new agent.

So that analog is, I think, something to to definitely keep your eye on.

Brett Canino, Senior Analyst, Stifel: Now you roughly share economics with your partner, Insight. 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 gonna look back and say that was a really good deal. So kudos to that. But how would you now describe the value that retains in Nick Timbo, and why should investors pay attention and reward a strong launch for this product?

Michael Metzger, CEO, Syndax: Yeah. Another great question, Brad. I think this is a how I'd characterize it, a high margin product. It's you know, the margins are good. The promotion and and the the spending that we 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 we pay out to our partner at Royalty Pharma.

That is a 13.8% royal synthetic royalty, as you pointed out, with with a cap. So at some point, once we pay back 2.35 times what they've given to us, which was, you know, 350,000,000, we'll have that capital ultimately ex expire and so or the royalty will. So I think the the upside longer term is certainly there with new indications and IPF pending. But in the meantime, with a high margin product, again, you know, the product is priced at a premium to the category. I think we have the opportunity to do quite well and, and, you know, with an ongoing royalty stream or an ongoing revenue stream.

So I think, again, this is a we believe going to be a a quite substantial product, blockbuster type product. And and with that kind of revenue potential and margin expansion, I think you have, you know, the opportunity to really participate meaningfully on a near term basis.

Brett Canino, Senior Analyst, Stifel: Okay. And then moving on to the additional studies being conducted with RevuForge. You have the frontline unfit AML patient study with Venet as a as a triplet being conducted with Hovan. Can you just discuss the status and expected timelines for that study?

Michael Metzger, CEO, Syndax: Yeah. So good news is we we've started that trial. So we we're opening we're opening sites now. Sites are open and, ready to enroll patients. And so we'll we'll say more about that on our on our, you know, May call.

But 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. And it's the first one of its kind. So we're the first to open up, that trial that in the unfit population on top of ANASA.

So exciting development for us and certainly the category. This will take time to enroll, so we haven't given very clear guidance as to when that will be completed. But it will take some time, several months, to get that fully enrolled. And many, many sites all over the world will be conducting that for us.

Brett Canino, Senior Analyst, Stifel: And then what regulatory endpoints and pathways do you think are available for U. S. FDA approval of that combination in the frontline unfit setting?

Michael Metzger, CEO, Syndax: Right, so 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 those opportunities for accelerated approval are available, they'll be available to us as well as other sponsors. So I think there we've looked at CR as a 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. So again, that is one potential that we're keeping an open mind towards.

Brett Canino, Senior Analyst, Stifel: And what is the status of the other combination with seven plus three chemotherapy for the patients who are fitter in frontline AML? And and why has that been less of a priority relative to the Venaza combo at Syndax?

Michael Metzger, CEO, 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, but it's not a lesser priority. We were the first to generate data in that category, again, addressing the high unmet need, and so that's 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 I data confirming dose. We'll have that data in the second half of this year, and 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 fifth setting. So whether it's MPM1, KMT2A, mutant populations, you have to look at it holistically. And 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 get there and generate data more quickly.

And so I think we'll be very meaningfully represented in these different populations, and 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.

Brett Canino, Senior Analyst, Stifel: Okay. Last for me then. You mentioned the second half data, Phase I, seven plus three combo. What would be a good outcome for that first data that you disclosed?

Michael Metzger, CEO, Syndax: Right. So just think about it historically, the response rates to seven plus three are expected to be around sixty percent for patients with KMT2A, closer to eighty five percent for patients with MPM1 mutations. And so we've seen data in addition to other MET inhibitors that can improve on these responses, so we'd expect to see similar when you add Reviforge to this regimen. And also hope to improve on the MRD rates, as well as the duration of response with the triplet. So for KNT2A, we'd also look to see an increase in the proportion of patients that are able to proceed to transplant, for instance.

Right? So that's an important point. And also, which percentage of patients or how many patients can receive Reviforge in the maintenance capacity. So I think there's some benchmarks, if you will, and so we hope to show some of that data until we look like we're moving in the right direction, at least in the early trials, which we we will have in the second half.

Brett Canino, Senior Analyst, Stifel: Okay. Great. Unfortunately, we're out of time. Michael, Steve, I wanna thank you so much for joining us at the event. We really appreciate it, and thank you everyone for joining and listening in.

Michael Metzger, CEO, Syndax: Great, Brad. Thank you so much. Appreciate it so much.

Brett Canino, Senior Analyst, Stifel: Thanks, Brad. Great. Thanks.

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