All right. Good morning, everyone. Thank you to those of you in the room, as well as those of you dialed in on the webcast. My name is Faisal Khurshid . I'm one of the senior biotech analysts here at Jefferies. We are here live at the Jefferies Global Healthcare Conference in New York. We're really pleased to have with us the management team of Syndax Pharmaceuticals, Michael Metzger, CEO, Keith Goldan, CFO, and Nick Botwood, CMO. We have a super interesting discussion to have across both commercial assets as well as a number of interesting recent updates from the company. Just to get us started, Michael, could you just give us an overview of the company?
Yeah. Good morning. Thanks for having us. Great to be here with you today. Yeah, the company's an oncology-focused, now commercial stage business, two products on the market, one for AML, Revuforj, AML and ALL, treating two subtypes, large subtypes of patients, KMT2A and NPM1 acute leukemia, areas of very high unmet need. We had a first-to-market product, Revuforj. It's a menin inhibitor. We've been on the market about a year and a half, so off to a great start. I'm sure you'll have lots of questions about the dynamics of our business. We are also in the market with another product called Niktimvo for chronic GVHD, indicated in the third-line plus setting, and also off to a great start in the first year. Both products are continuing their development.
We are active in frontline trials, registration trials for both products and have multiple readouts this year across both programs in combination with the standard of care agents, as well as advancing both to frontline as quickly and expeditiously as possible. We are in excellent shape as a business and as we've made that transition over the last, call it a year and a half.
Got it. Excellent. To just start things off, I actually wanted to start with your most recent announcement, which was just this morning, that you guys took out a new convertible debt facility. Could you talk to us a little bit about the rationale for doing that and how that positions the company going forward?
Sure. Maybe, Keith, do you want to take that question?
Yeah. We've been giving guidance that we're keeping OpEx flat and that the company's fully funded just on the balance sheet we had as of yesterday, and nothing about that changes. It was $250 million in five-year convertible notes at two and a quarter up 35. We're really happy with the terms. The catalyst was an unsolicited inbound from a fundamental long investor. That, like I said, that catalyzed the financing. We were able to build around that anchor order and close the deal yesterday. We privately marketed the deal. We did not take any market risk. It was the cheapest capital the company's ever had the opportunity to access.
Yeah. Maybe I'll just add that really sets us up for success. I think the offering was, as Keith said, oversubscribed and opportunistic, but importantly, we have what we've described in our R&D day, which is coming up in about six weeks from now. We'll talk about our early pipeline, which we have every intention to and we're excited to invest in, as well as some very late-stage important readouts for IPF is one. I'm sure you'll have questions about IPF today, but that's an important readout at the end of the year. We anticipate that we will have investments to make and that the return on capital will be significant, so we want to be ahead of that and obviously take any financing overhang off of the company and be ready to really get going into those programs.
That's a future discussion around our pipeline and so forth, but want to be very clear that we have very important uses for the capital.
Got it. I have one clarification point, then one thing to kind of just push you guys on. Keith, you mentioned that it was an unsolicited inbound. Was that unsolicited inbound specifically for debt or for equity and then became debt, or can you just talk a little bit more?
Actually, specifically for convert.
Got it. Okay, interesting. With respect to the timing of this, like Michael, you mentioned that one of the things that the company may have to prepare for is running a phase III program in IPF. If that's the case, in terms of timing of doing this, why not wait until the other side of the phase II IPF data?
Well, for one, we're quite confident that we'll have a positive result, and as I think if you are familiar with how companies are built, they're not built one second at a time. You have to be prepared, and we're preparing to really go forward into phase III, and that's a significant endeavor. Those investments need to be made as soon as possible. I think we're in a good position rather than waiting and having a financing overhang. Everybody's anticipating a financing. I think we wanted to make sure that we had the capital that we need to execute.
Makes sense. Okay. Just remind us with respect to spend on Niktimvo or axatilimab for R&D, how does that work with the Incyte collaboration?
Sure. Keith?
For the Incyte collaboration, research and development expenses are split 45% Syndax, 55% Incyte for all development that's for a U.S. indication. Outside of the U.S., Incyte picks up 100% of development and regulatory expenses, and we do a royalty.
Got it. Okay. That happens as you do the trials? If you do a phase III in IPF, Incyte would pick up the bill for 55% of that?
For 55%, yep.
Got it. Okay. Makes sense. Rolling along with your other kind of more recent announcements, I think you guys recently announced that you'll be hosting an R&D day in the near term. Can you set expectations for why you guys decided to do that and what investors should expect?
Yeah, very exciting, and I'll let Nick give us some detail.
Thank you, Faisal, nice to be here at Jefferies. Appreciate it. Looking forward to this R&D day. We have a lot to update on. Just to start with, to remind you, we have an exciting and ambitious plan, lifecycle management plan for revumenib, we're running two large phase III studies for that, we'll update a little on the status of those. We also have an important program, with axatilimab, with some important upcoming catalysts that we'll go a little bit deeper into. Of course, there's our idiopathic pulmonary fibrosis phase II, which we've guided towards reading out in the fourth quarter of this year. We'll update on that. That's an important part of our development programs. Also an important study in the frontline GVHD study, which is also guided towards reading out in Q4 of this year.
We actually slightly accelerated the timelines for that study, because of the enthusiasm to enroll into it. That's an important potential steroid-sparing regimen in frontline GVHD. A very important part of lifecycle management for that asset as well. In addition, we will be updating on some of our early-stage assets, which we haven't talked about a lot to date. We do have a pipeline that we're excited to update on. This is very much playing to our strengths as an organization. We have remarkably strong R&D capabilities now. We have a proven track record of identifying exciting, differentiated assets. Translating that science into the clinic with innovative development programs, taking it through to registration. That's how we developed and approved and commercialized revumenib and axatilimab. We're hoping to replicate and expecting to replicate that model with these early-stage assets.
These are oncology-specific, targeted precision agent approaches that we will update on at the R&D day. We are really excited to unveil those programs that are very complementary and playing to our strengths as an organization.
Excellent. Great. Let's dive in on Revuforj then. How has the launch progressed to date, and can you set expectations for 2027 and how investors should think about the cadence of the launch through the year?
Launch has gone well. As you know, last year, we did $125 million in sales. Last quarter, nearing $50 million in sales. About $49 million. Run rate on the business is about $200 million. Off to a fantastic start if you measure us against any other AML product, in terms of scripts, in terms of new patients, in terms of revenue, we've done very well. That will continue. 2027, or 2026 rather, will be a very good year. We expect growth in both KMT2A new patient starts, as well as patients going to transplant and then returning for maintenance. The time on therapy should lengthen, and that should be a positive driver for Revuforj for KMT2A. The NPM1 business is the newer indication.
New patient adds are going to be, we believe, significant this year, and patients we expect to stay on drug as well for a meaningful period of time. This is a growing business, a larger patient population than KMT2A, about two to two and a half times the size in the relapsed/refractory setting. We expect the business to be a meaningful contributor to the mix of new patients as well as revenue, relative to KMT2A. The business overall will grow, and we expect to continue to have dominant share relative to competition that is already on the market, and new to the market as well. In summary, launch is off to a great start, and we're expecting good returns in this calendar year.
Got it. Great. KMT2A, I understand one of the main drivers there will be patients coming back from transplant. Can you walk us through the dynamic of, in your recent quarters, what percentage of patients have you seen going to transplant, and what gives you confidence in a portion of those patients coming back?
Yes. The patient dynamic for KMT2A, I think we've talked about this a lot and it continues to be a very interesting dynamic where you have patients getting therapy and a high degree of response for many of these patients. In our clinical trial, we saw about 2/3 of patients getting to response, and we were treating third and fourth-line patients. Those response rates are, we believe, going up relative to patients being treated in the second and now third line predominantly, and more transplants. The earlier you treat patients, the better they do, the higher the response rates and the opportunity to go to transplant. Early on in the launch, we were at about a third of patients going to transplant. Now we're at about 50% as of this past quarter, 50% of the patients going to transplant, which is a great outcome for patients.
As expected, patients are getting maintenance, and that number has gone up over time as well. About 45% in this quarter of the patients who are getting transplanted are actually going to maintenance. We expect that number to grow. The 45% will grow to, we believe, somewhere in the neighborhood of 70%-80% of patients getting maintenance over time at steady state. When exactly that is, we don't know, but it'll take a little bit of time, and it's based on speaking to physicians, also what our prior data indicated in terms of patients going back on maintenance from our clinical trial. We're very optimistic that that will continue to be a very important driver of the KMT2A business, and, more importantly, just really important and very good for patients.
Got it. In terms of the 45% are coming back from transplant now, you want to increase that to 70%-80%. What are the levers that allow you to do that given some of the nuances on not explicitly having a maintenance indication on the label?
Yeah. It's a very important question, and I'll say in one word, it's data, and data and experience. Maybe, Nick, do you want to talk a little bit about some of that data?
It's important, Faisal. I would just remind you again, you've made the point, this is not an indication that we have. We're not promoting maintenance. We haven't proven the benefit of maintenance. This is very much at physician and patient discretion. What our responsibility is to generate the research and support the research and data that will create informed decision-making. At the moment, that's through providing data. We hope in time that'll be through informing guidelines and potentially labeling as well, and that's our ambition to do that. In the meantime, it's very much a physician's discretion. We are generating, as the leaders in the menin space, I would say, a leading body of evidence that helps inform that decision.
There is a very reasonable clinical proposition that if a patient has responded well to revumenib pre-transplant and then gets a response and goes on to transplant, these patients tend not to do very well. There is a high rate of relapse. We recently, in collaboration with MD Anderson, presented a series of patients, this was adults and pediatrics, at ASCO. Around 24 patients that went on to transplant in their experience and then went back onto a maintenance therapy afterwards, and a few conclusions from that study. I think number one and most importantly, it is feasible and tolerable to treat patients in the maintenance setting. Probably the most common adverse event, as you would expect for patients that have just undergone a transplant and while they are allowing for engraftment, is cytopenias.
We did see quite high rates of thrombocytopenia, and indeed, three patients discontinued their revumenib therapy because of thrombocytopenia. However, in the main, it's manageable with dose adjustments and dose interruptions, and physicians are learning how to do that. We will be presenting data later in the year about what's the best way to optimize therapy. The thrombocytopenias are manageable. They can be monitored, and the patients tended to do quite well. It is feasible to do it. That's number one. Number two is, even though we haven't proven this with a randomized controlled trial, our single-arm real-world evidence or experience as it is from clinical trials, I should say, pooled data from clinical trials, does support the use.
The one and two-year overall survival rates were around 90%, which compare very favorably to the historical controls that MD Anderson presented, where you would expect about 50% of patients only to be alive, or 50%-60% at one and two years respectively. It is very suggestive that you're creating benefit. In a setting where once you get into the relapsed setting, the chances of cure and long-term remission are very difficult, the opportunity for a patient to be treated is quite important. We'll have more data at EHA. We'll have a series from our own AUGMENT-101, and we'll also have some real-world data from Dana-Farber that also shows the opportunity and the feasibility of treating patients in the maintenance setting. As we continue to generate data, we'll think about updating guidelines and our registrational strategy.
Got it. If I remember correctly from the ASCO session, the discussant kind of raised this question of whether continuing to treat in maintenance is over-treatment, whether there's some debate to be had on that. I'm just curious if you can provide your perspective on that as well.
Well, I think perspectives on that vary, and I think that's reasonable because this is an evolving area. My sense, and many of the thought leaders we've spoken to and the team has spoken to, is that given the high rates of relapse and that these patients tend not to do well, this is acute myeloid leukemia we're talking about. Many of these patients have poor prognosis. If a maintenance therapy that can be tolerated for out to one to two years is going to increase the chance of being alive at one and two years, which these data would suggest it is, that's a very important discussion, I think, to be had with a patient. For now, we're going to continue to generate data to support informed decisions and really help in that regard.
The data we've generated today, I would suggest, are supportive, and that's what physicians are tending to do. In the real-world series we presented from Moffitt, from Dana-Farber, you'll see some more data later in the year. That is the tendency now to treat these patients, particularly if they're high risk with a high chance of relapse and early mortality.
Got it. Then across the various academic partner studies that you're doing for maintenance, can you give us a sense for what quantum of data and from what study do you feel would be sufficient to get maintenance recommendation into NCCN guidelines?
Maybe a couple of comments on that. We have maintenance built into many aspects of our program. Real world, we've talked about the series we're presenting from our clinical trial experience. We've talked about two other data points. One is we do include maintenance in our pivotal phase III studies. Both the REVEAL study in combination with intensive chemotherapy and the study in combination with venetoclax, where transplant will be less common. Patients are allowed to go on to maintenance revumenib in the context of that study, and we can analyze and explore those data from those pivotal trials. That will be one data point. The other is we just announced on ct.gov our collaboration, again, with the Dana-Farber Cancer Institute in Boston, which is called the MAINTAIN Study. It's now on ct.gov.
This is a 144-patient placebo-controlled randomized study specifically designed to isolate the effect of maintenance on patients who have their first transplant. We're excited about that collaboration. It should be up and running towards the latter part of this year, and that is specifically identified to really isolate that potential benefit for patients.
Great. Then, Michael, you had mentioned strength in the NPM1 side of the business, and I think you mentioned your incumbent position versus the competitor, as well as duration of therapy being key levers on that. On that first part with respect to your competitive positioning, can I ask you to just kind of double-click into that and what your current understanding is of market share and your expectations there going forward?
Right. The way I like to look at our business, I look at it as relapse refractory business. KMT2A, NPM1, other lesions that we are also treating that are perhaps not on label but may have an impact on the disease. I think the business itself as of the quarter, as I mentioned, we did about $50 million. It's growing and quite significant. I think our competitor did about $5 in its first quarter. The order of magnitude here is quite different, and I think the benefit of having the broadest set of indications for KMT2A, NPM1 adults and pediatrics gives us a big advantage. I think just thinking about that as the backdrop is important. In terms of our market share for new patients, I think it depended on how you look at it.
It's early days to be counting that just as the data will pan out. I think we'll know more over the next two to three quarters where things stand. We have a dominant position. I think it's very clear based on the numbers of what I just quoted, that we're in a very different position. The NPM1 business is about $15+ million for the quarter, that also gives you another dimension of how to compare us versus our competitor. I think if you look about at our market share in any of the measures, I think it's completely different. We have a dominant position.
Got it. Makes sense. I want to talk a little bit about the phase III that you have going, and Nick, you alluded to these EVOLVE-2 and REVEAL-ND. Can you remind us the design and endpoints for both of those?
Yeah, absolutely. These are relatively straightforward designs starting with REVEAL. This is addressing the question of does revumenib add to intensive chemotherapy? Classical 7+3 chemotherapy regimen in NPM1 patients who are fit to receive intensive chemotherapy. It's a two-arm study randomizing rev plus 7+3 against 7+3. It has two dual primary endpoints. They're independently powered. Either one of them could be positive. One of them is MRD negative CR assessed using bone marrow NGS, and then the other dual primary endpoint is event-free survival. It's enrolling well. We're focused on multiple site activations internationally, including Asia. We're very happy with the momentum behind where that study is. The other study is called EVOLVE-2. This is a study we're doing in collaboration with the HOVON group in Europe. It does also include sites in the U.S. This is for patients not considered fit for intensive chemotherapy.
It's on a background of Venclexta. It's Venclexta plus or minus revumenib. It has dual primary endpoints independently powered. One of them is complete response. This has been used before by health authorities for accelerated approvals, actually to support the approval of venetoclax. The other dual primary endpoint is overall survival. Recognizing the survival for these patients who tend to be elderly and unfit for intensive chemotherapy is of the order of 14 months. Overall survival is the other dual primary endpoint to see if we can actually improve survival for these patients. Those are two studies. The HOVON study was actually the first randomized study to start enrolling. We actually started that study back in May 2025. We have good momentum behind it. Multiple sites now activated internationally and enrollment's going well.
We're just laser-focused on completing the enrollment and then getting to readout.
Great. Then can you clarify across both the Venclexta combo and the 7+3 combo where you see your competitive timing or your timing versus the competitors? I feel like everyone says that they're first.
Yeah. Well, I think good news is we started first, and we have good momentum. I think we bet on ourselves in terms of our ability to get there. I think we were the first ones. We're pioneering the space. As you know, leadership is important, and all the data that we'll be generating over time will help physicians look at these combinations as the future versus just an experiment. We're quite confident that not only we'll enroll these trials quickly, but we'll be first and have an equal dominant position in the first line as we have in relapse refractory. We've best profile so far. The data supports all that. We're confident that we'll get there.
I'd maybe just add one point, Faisal, to say there are some innovative elements in terms of the design of these studies that we maybe haven't spoken about publicly because it is a very competitive space, but we think that in addition to just the execution will position us strongly for a first readout.
Great. You mentioned that CR is a validated endpoint for accelerated approval in the unfit population. You also mentioned that MRD negative CR in the fit population is one of your dual primary endpoints. Understand if you want to plead the fifth, but just curious if you're willing to comment on extent of regulatory buy-in you see on MRD negative CR for fit AML.
Yeah. This I think is a little bit less of a competitive space because I think that endpoint to be used as a surrogate to support approvals will just help the industry and most importantly will help patients. We're working in a collaborative way with consortiums and academic groups and regulatory bodies to support that endpoint as an endpoint that does actually direct towards improvements in EFS and OS ultimately. I think that will just serve the community well. This is not so much a competitive space. We're very much on the leading edge of the evolving science, and we think that whilst it hasn't been used to date as an endpoint to support regulatory approval, we're feeling quite confident in the time between now and that study reading out that study could serve as an endpoint to support accelerated approval.
Our focus is on executing the study and make sure that we stay on the cutting edge of the science as it continues to evolve.
Got it. I think there's precedent for this in ALL. Is that correct? Does that have read through to AML?
It does, and we're using lots of precedents, including the use of MRD in myeloma. The space is evolving quickly and ctDNA in solid tumors. The landscape is evolving, and we think that AML could be the next to leverage some of these endpoints to show that they actually. As you would anticipate, because we know if you get good clearance of MRD, particularly sensitive tests like MRD negative tested in the bone marrow, which historically you probably would only see 40%-45% of patients roughly would get that clearance based on bone marrow from intensive chemotherapy alone. We feel that there's quite a big delta there to improve on, and if you can show a meaningful benefit, then that would translate into event-free survival and ultimately overall survival, and that's our ambition.
Got it. Understanding that the comps here are that 40%-45% for chemo, do you guys have a sense, based on any preliminary regulatory discussions on what level would be needed, or either to be considered clinically meaningful or for regulators to consider for accelerated approval?
Yes. That I'm not going to comment on because that is sensitive, but that is obviously a discussion we're having and how big the delta would need to be to be meaningfully predictive of clinically relevant endpoints.
Got it. Let's shift gears then, we have a few minutes left, to Niktimvo, your GVHD and potentially IPF program. Starting with GVHD, you mentioned earlier in discussion that you have the phase II study in earlier line settings. They moved up the readout to come later this year. Can you remind us what is the study design for that and the importance of that for the ultimate development plan for the program?
Sure. Yeah, thank you. I'd be happy to. This is an important study just in terms of its clinical significance. Patients traditionally are treated with initially high-dose dexamethasone, and high-dose dexamethasone comes with high levels of morbidity and there are many side effects. This is a study that was designed to see if there's an alternative to having to give high-dose dexamethasone. It's a three-arm study with a control arm of steroids and then one arm which is a JAK inhibitor, Jakafi, and then the combination of Jakafi and axatilimab to see whether you can isolate the contribution of axatilimab to JAK inhibitors alone. Our hope and expectation is both of the experimental arms will beat dexamethasone, and then you'll see the additional benefit from the combination of axatilimab and Jakafi. It's a phase II, 40 patients per arm. The endpoint is response rate at six months.
The benchmark for dexamethasone response rate would be about 40% using standard NIH criteria. We're well-powered for detecting a meaningful delta over 40% with the combination, that's what we'll look for. It's a phase II, it would inform future development programs, it could present quite a meaningful alternative for patients to not have to have dexamethasone. We reported out some tolerability data just at the recent congress at ASCO that showed that there's really very little, if any, additive toxicity to JAK alone when you add axatilimab. That's consistently shown a very clean profile with treatment-emergent adverse events actually very consistent across the three arms, which is encouraging. We'll see. We've guided towards Q4, that's the design.
Great. You mentioned 40% is the kind of published benchmark for dexamethasone. Do you have an expectation for what ruxolitinib will do in that setting?
Yeah. Broadly, I would suggest you probably want to see a delta for it to be meaningful of towards 60%.
Got it. Can you talk about the extent to which this would de-risk or validate your ongoing early line study and the timelines associated with the early line study you have ongoing?
Yeah, that's a different study. It's a different hypothesis. That is a pivotal phase III, which we'll read out a little later, so that will be more towards 2028. That's a large randomized phase III of asking the question whether axatilimab actually adds to dexamethasone. Some patients may need the steroids, and then the question is, does CSF1R antibody add to that? There's a very good mechanistic rationale why steroids and CSF1R would be complementary. One more targeting T cell immunity, the other one very much directed towards macrophages, both inflammatory and fibrotic. Potentially nice synergies in the treatment of frontline GVHD by combining axatilimab with dexamethasone. That one has an event-free survival endpoint, and we anticipate reading out in 2028 timeframe.
Great. We have a couple of minutes. I just want to touch on IPF. You have this readout coming up in the fourth quarter of this year. Very novel hypothesis for axatilimab. Can you remind us what gives you confidence and validates the hypothesis here?
Go ahead. Yeah, there are lots of things, and we're excited about this readout. This is a placebo-controlled blinded study, so we'll wait and see what it shows us in Q4, but there's a lot of preclinical and clinical data that would support the hypothesis again of CSF1R inhibition in idiopathic pulmonary fibrosis. There are compelling bleomycin-induced mouse models. We have very nice data showing that CSF1R actually reduces inflammatory cytokines like TGF-beta, TNF, IL-8, and others, which is encouraging. We saw very marked improvements in one of the manifestations of GVHD, which is called bronchiolitis obliterans syndrome, which is the lung manifestations of GVHD, showing that those patients at the approved dose had a 50% improvement in terms of response rate and improvement in their symptoms. Very encouraging data there.
We've also seen, and the IPF docs were actually most excited about this, very good wound healing in sclerotic skin lesions, which is again a manifestation of GVHD. Sclerotic wound healing suggests that you're both impacting the inflammation and the fibrosis, and that's one of the fundamental hypotheses about going into IPF. Lots of both clinical and preclinical data that supports this. We also know that patients with IPF that have high levels of monocytes and macrophages tend to have a worse prognosis, implicating them in the pathogenesis of the disease. We'll see how that study reads out in the fourth quarter, but we feel optimistic about the hypothesis supporting it.
Great. Okay. I think that's all we have time for. Thank you guys so much for your time today.
Great. Thank you so much.