Syndax Pharmaceuticals, Inc. (SNDX) Earnings Call Transcript & Summary

Okay. Well, thanks for joining. Good morning, everyone. I'm David Dai. I'm the biotech analyst here at UBS. Thank you for joining our fireside chat with Syndax Pharmaceuticals. It's a great pleasure to welcome the executive team, have Mike Metzger, Chief Executive Officer; Steven Closter, Chief Commercial Officer; and Nike Botwood, Chief Medical Officer. Thank you, Michael, Steve and Nick. I appreciate you joining us.

Yes. Thanks for having us, David. Always a pleasure to be here with you and UBS team.

That's great. So with that, for someone who are new to this next story, could you give a quick overview of Syndax, your lead programs as well as any kind of overall company strategy?

Sure. First of all, thanks for the introduction. We're at a very exciting point with the company. So Syndax is now a commercial stage company focused on oncology. We have 2 commercial stage assets, which we've developed from the very beginning all the way through now have launched in the last year. We've had gotten off to a fantastic start. Revuforj is our asset in AML and ALL for acute leukemia. First of its kind, first and best-in-class menin inhibitor, selective menin inhibitor, first indicated for KMT2A, acute leukemia, which is about 10% of the overall population of AML and ALL. And now newly introduced and approved is NPM1, is another large subsegment of the population in adult AML and pediatrics, and that affects about 30% to 35% of AML. So now we have a very broad offering in adults and pediatrics, AML, ALL, KMT2A and NPM1, roughly 40% to 50% of the population, a very large opportunity, about a $5 billion opportunity, which we're exploring. And we have a fantastic -- we're off to a fantastic start there. We'll tell you more about that. Our second asset is Niktimvo, which is for chronic GVHD, another first-of-its-kind CSF-1R antibody directed at third line plus chronic GVHD patients. We launched that product in February of this year and also off to a fantastic start. Both products are outpacing all the metrics in their respective areas. And so we are very proud of what we've done so far, but we're just getting started. So the company's strategy is to develop products in oncology, and we've done that successfully now with these 2 products, and we are expanding them. So we're moving quickly into frontline trials to bring them to newly diagnosed patients in combination with standard of care therapy, and that goes for both assets. And beyond that, we'll look to move into additional indications for both of these assets, not only newly diagnosed patients, but for instance, with Niktimvo going into areas such as IPF for patients who have fibrotic disease of the lung. So much to discuss, but we're off to a great start and here to answer your questions.

That's wonderful. Very exciting, a lot of progress and a lot of excitement happening over the next 12 months, too. So maybe let's start with Revuforj for a lead program. It's almost a year into launch in the KMT2A space, and you just launched the NPM1. Maybe just help us understand some of the ramping. How is it going so far? Could you share with us patient also physician feedback and experience on Revuforj so far?

Feedback has been fantastic. I mean we had -- again, we had -- for NPM1, the second indication, we had the opportunity to get the drug into guidelines. So we were able to -- ahead of approval, which is at the end of October, based on published data, we were able to access the guidelines. Our field medical team initiated work with the guidelines and talking to physicians about the new indication. And then we got approval, which was a broad indication for relapsed/refractory disease in both adults and pediatric patients. So the feedback from physicians has been fantastic. They're eager to put their patients on. The drug is well tolerated and very efficacious. And this is an efficacy-driven market where physicians really are focused on getting their patients into remission as quickly as possible. Our drug does that very well. And so they're excited about this new indication because it extends the population and allows us to really do more with the drug. And so, so far, so good. We're ramping quickly, and we expect to have a good fourth quarter and into next year as well.

Excellent. Excellent. So on KMT2A, right now, more than 750 patients have been treated so far, 1/3 of them have progressed to transplantation. As you're treating more patients, as you mentioned before, and the healthier patients, you can imagine, do you envision more patients would potentially be put on transplantation?

I think the simple answer is absolutely yes. There's no reason to think that with a drug that gets patients to a very robust deep response quickly, and drives more patients to transplant, why physicians wouldn't be apt to transplant more of them and also put them back on therapy. So the opportunity here is not only to drive patients to transplant, but to bring them back in a maintenance capacity and put them on therapy and keep them there in remission for an extended period of time, months, if not longer. And so we're talking about a year to 2 years potentially of maintenance, which is a very significant driver of this business, specifically for KMT2A patients who have the ability to -- there's younger patient population, more of them are fit for chemotherapy and for transplant. And then you bring them with Revuforj, you bring them back on maintenance, that could be potentially a very long period of time that drives the revenue of that smaller population of patients, about 10% of AML. For NPM1, they do the same. They do -- this is an older population, but they do transplant them. And so the ability to treat them earlier, patients tend to do better, stay on therapy longer and potentially get maintenance as well. So that's the paradigm that these physicians really would like to pursue. And with a drug like Revuforj, they're able to do it as well as possible.

Got it. Got it. And so one thing you mentioned was that some patients went into maintenance therapy. And so far, we've seen about 30% to 40% -- based on the most recent metric, 30% to 40% of patients were put back on to Revuforj after transplantation. How do you think this number would change over time? And what's your sort of expected percentage at steady state?

It should increase, really 2 factors. One is physician experience, the ability to -- once they put a patient on maintenance, they tend to put them on maintenance again, right? They have a positive experience. And we've heard that from physicians all along that they expect to put their patients on maintenance as much as 70%, 80%, we expect potentially over time could go on maintenance. That's very different than 35% to 40%. So I do think it's a matter of experience. It's also a matter of time. There's some patients who haven't just been given enough time in our very brief commercial experience to go back on therapy yet. So you got to give them a little bit of time. It takes 3 to 4 months once they have their transplant to engraft. So some of those patients are just starting to get to that period of time where they can go back on. So the 2 factors, time and physician experience, and I think that favors a much higher amount of patients going back to maintenance.

Is there a number in terms of what the steady state maintenance therapy is going to look like?

Well, I said 70%, 80% is a possibility, and we don't know based on our clinical experience, it's at least that high. So we'll see. We'll see what happens. But I do think that the building experience that we have should drive that number up meaningfully.

Okay. That's really good. And tell us a little bit more about those kind of patient journey around that. How quickly do you think these patients can be put on maintenance therapy based on the current experience with respect to patients getting on the CR and MRD-negative CR and then transplantation and then eventually get a maintenance. What's sort of time line look like here?

It's -- look, the time line has been pretty consistent from our clinical experience and now through our commercial experience where you have a patient gets to response rather quickly, first response, about a month, best response, about 2 months, 2 to 3 months, they get their -- at that point, they get their transplant, so they're in remission. They receive a transplant, and they're going through that engraftment period where it takes time for the bone marrow to come back and fully populate their blood cells. And so you have about 3 to 4 months of time where they're off Revuforj and they're pausing treatment and then they return to maintenance thereafter. So it's from start to resumption of therapy, it's somewhere in the 6-month range where they'll start to get...

Got it. And do you think this number will also change over time too as patients get a little more comfortable with Revuforj, physicians get more comfortable with Revuforj going forward. Do you think this number will evolve over time as well?

Maybe Nick can answer that question.

Well, I think it's a fascinating area actually and the science is evolving. I mean there's increasing data that supports the concept of maintenance after transplant. And I think physicians are getting more familiarity with how to dose. You have to remember that after transplant, patients marrows after engraftment are quite delicate. And so you have to have familiarity with dosing to ensure that the drug is tolerable. So we're gaining a lot of experience now with managing cytopenias. And one of the benefits, I think, of Revuforj is that it does allow a little bit of flexibility in the dosing, and so physicians are getting to know how to do that. But there's also some quite fascinating science in terms of mechanistically why it might make sense to put a patient back on Revuforj to give that increased chance of event-free survival. We're actually going to -- at ASH, have some quite interesting series of real-world evidence. We promised data coming from our commercial experience now every year of approved and ASH will be the first time we've had the opportunity to present some of that data. Two series, one from Moffitt in Florida, another one from the MD Anderson, interestingly, from the pediatrics Department of MD Anderson that they also have experience in adults. But in that series of about 10 patients that went on to get maintenance after transplant, we have a 1-year event-free survival of 100%. And that's really encouraging for this pediatric population where normally the relapse rate would be quite high. But on maintenance, all of them tolerated it very well. Patients were able to dose interrupt or even reduce if necessary to manage cytopenias, but to be seeing preliminary efficacy that looks as promising as it does, as those generated continue -- as those data continue to be generated, I think it's just going to increase the desire to have patients back on the Revuforj after transplant. So already, we're beginning to see that and publish it, and that's very exciting.

Yes. And I think another question just around the duration of therapy. I think most investors care about right now. Just help us understand where it is now? And how do you think it's going to evolve after patients or more patients are getting on to maintenance therapy?

Yes. What we've said is this first year of launch, we expect the duration of therapy in the order of 4 to 6 months, and that factors in mostly new patients starting and patients staying on therapy and then dropping off and going to transplant and for a very small portion of the year being able to come back, and we expect that to accelerate in the future years. So this year, factoring all that in 4 to 6 months average time on therapy for this year and then it extends next year with the introduction of more patients going to transplant coming back for maintenance, probably more in the range of 6 to 12 months next year.

And how do you think the number will evolve over time as well?

It could get longer. I mean I think there's no upper limit to what could happen. I think we're already setting a very high watermark for other therapeutic classes within AML. You haven't seen the ability to extend to maintenance with FLT3 and IDH. You just don't see it as much as you do with KMT2A, for instance, where you have a younger patient population and you have a medicine like Revuforj that drives to remission so quickly and enables the transplant. So I think this is a very -- this population is specific for this KMT2A and NPM1 for a drug like Revuforj to really impact and drive maintenance. So it's a different capacity than you've seen with any of the other targeted therapies within AML.

Got it. Great. So now you recently got approved for NPM1 patients, but we did see an updated black box warning of [indiscernible]. Maybe just help us understand the decision of the FDA to include or to update the black box warning to include this [indiscernible] case? And how do you think this might impact adoption in NPM1 setting?

I'll just make one comment, and then I'll pass it to Nick. I don't think it will make a difference at all. In fact, this is -- physicians have had fantastic experience prescribing the drug for KMT2A patients and some for NPM1. They've done it off-label. And so this body of experience speaks for itself. We've done extremely well from a sales perspective, but also introducing this new therapy to physicians and they want to use it. They feel it's well tolerated. This is very much standard of practice for them. They're not doing anything out of the norm to introduce and use Revuforj, and they feel very, very comfortable with it. So our experience speaks for itself. And maybe I'll pass it to Nick specifically around.

No. Thank you, David. QT prolongation is not new for Revuforj. Frankly, it's not new to prescribing physicians in AML. There are many drugs in the treatment of acute myeloid leukemia that have significant benefit that cause QT prolongation. So physicians have a lot of experience in managing it. It's been a warnings and precautions as we've significantly expanded our use of the drug, both in our clinical trial setting. In the label now, we have a safety data set of nearly 250 patients, and we've exposed many more than that, including commercial and compassionate use. So as we've expanded, we did identify a case of [indiscernible] that met the criteria for a warning. But the guidance in terms of how you manage QT is exactly the same. You do weekly ECGs, you optimize electrolytes and you make sure patients are well managed. And by doing that, we've really been able to mitigate any potential risk of the clinical consequences of QT prolongation, and that's really important for prescribing physicians. But I think what's really driving this is efficacy in a setting where we're talking about relapsed/refractory AML. These patients have sadly very short life expectancy. What you want to do is you want to get these patients into response, give them a chance of a durable remission and potentially even a transplant. So that's very much in their mind. I don't think that the management of QT is really a big consideration in the best selection of a first-in-class agent, which has really changed -- transformed, I would say, the standard of care in relapsed/refractory AML. So it's really very well managed and not a concern to prescribing physicians.

Yes. I would just amplify the fact that this is an efficacy-driven market. Physicians care, first and foremost, about what's -- which drug is going to get their patients to remission. And our drug does a fantastic job of that. And relative to any other menin inhibitors potentially coming behind us, I don't think anybody has seen data that is reminiscent of what we've been able to show in monotherapy or even in combination. And it makes the choice quite easy for physicians. They monitor the same way they were monitoring before. So the label doesn't change that.

Got you. Got it. And since the approval, you had a couple of weeks, right, of bringing the field team with the [ updated ] label to physicians. I'm curious how has the feedback from physicians so far? Maybe Steve, you can talk about this, what has been some of the feedback from the physicians on the NPM1, especially on the NPM1 setting, how they're viewing the label and how they're treating patients so far on the ramp?

Yes. Good question, and there's a lot of excitement. We haven't had a lot of time. NCCN guidelines were granted in the third week of September, a little lift there, a little bit more visibility, but awareness is very high, certainly on the condition and certainly on the drug. We talked about the KMT2A launch and the 750 patients that have been on since launch. There's been over 2,200 prescriptions, and that's against an audience that's smaller than most other targeted AML therapies. So it's off to a great start. The drug has done incredibly well. Physicians can easily identify patients. And the treaters that have used the drug so far, and it's a very broad patient population, there are hundreds of accounts that have had a lot of experience. So there's no challenging -- no challenges to getting patients on therapy. And it's that same treating audience and it's physicians, it's nursing staff, it's distribution, it's pathology within these accounts, that broad experience they have so far with Revuforj, they're going to see NPM1 patients. So that will translate incredibly well. So early days, patient population, as you know, is bigger than KMT2A. We'll be excited to share results at the end of the quarter, but we're off to a great start.

David, I'd maybe just add one thing that familiarity is so important. But also we know that physicians like to use the drug in different settings and in different combinations. And to support that, I mean, obviously, we don't promote in that setting, but to support clinical practice, combinations of drugs is really important. And we're going to have a really outstanding presence at ASH this year. We're excited about that. We're going to have 12 abstracts for revumenib, 23 if you include Niktimvo. So really strong scientific leadership. Included in that, as I already mentioned, is some real-world evidence. The real-world evidence would suggest that in academic centers like Moffitt, they like to use Revuforj in combinations. That's their choice because they think it gives them a higher chance of getting a patient into response. That's important. And our focus has been ensuring that we're doing the right research, working with the best sensors with the best clinicians to generate data that supports how physicians want to use Revuforj and generate that data. And I think ASH is going to be a testimony to how we're doing with that, more to come. And that's really important that we continue to lead and innovate and provide those data to ensure the best practice.

That's a great segue to start talking about some of the combination strategies you have for Revuforj, especially moving to frontline. So maybe making -- just tell us a little more about some of the strategies and clinical development plans you have for Revuforj in combination with various different therapy standard of care in frontline setting.

I'm incredibly excited about that. I mean, as I said, we transformed the standard of care in relapsed/refractory. Our intent is to continue to lead and be first and transform the standard of care in newly diagnosed patients. That's where we believe we can have the greatest impact, and we can bring more patients potentially even to cure. So it's been a focus of our program throughout. We're going to have some more very important data at ASH. As we think about developing Revuforj in frontline newly diagnosed patients, clearly, you need to have established data in combination, both to establish tolerability to confirm the dose you want to take forward and also show preliminary efficacy. So if you start perhaps with the unfit population, patients not considered eligible for 7+3 or intensive chemotherapy, that's really been a preliminary focus of our program and we have generated compelling data now from the Beat AML study, and then you'll see some updated data at ASH from the SAVE study, showing really compelling tolerability, but importantly, efficacy in combination with VEN and an HMA, whether that's IV or oral. And those data gives us and our collaborators very high degree of confidence that we can get a successful Phase III in combination with ven/aza. And we know that ven/aza is increasingly being considered a standard of care, certainly for unfit patients, but potentially even fit patients as an alternative to intensive chemotherapy because of the reduced morbidity. And that's incredibly exciting for us because we've demonstrated such compelling data across NPM1 and KMT2A. And then when you think about intensive chemotherapy, patients sit for intensive chemotherapy, we're going to update some important data at ASH showing our Phase I data, both with some work we're doing with the NCI and also Syndax sponsored Study 708 that shows, number one, you can combine very effectively with intensive chemotherapy. We have shown that we can combine at the current recommended dose of Revuforj, which is important. That's the dose we'd like to take forward into Phase III, and we'll be confirming that shortly. But really importantly, compelling activity. We've seen 100% complete response rates in KMT2A and 100% MRD negativity. So when you combine Revuforj with an intensive chemotherapy regimen, you do get both a tolerable regimen, but importantly, really striking activity with very high percentage of patients actually going on to get a stem cell transplant. So we have guided previously that we're planning to start our REVEAL program focusing on 710, which is the NPM1 population by the end of this year, so very soon, and that study is posted on ct.gov. And then in terms of the KMT2A population, more on that to come, but we're very encouraged by the data we've seen both in combination with intensive chemotherapy and ven/aza for that smaller population. And we really think we're leading in that space because, again, we've seen 100% CR and 100% MRD negativity, which is extremely encouraging. So very robust plans to get us registrational programs in the front line. And then that is obviously supported again by a variety of collaborative and investigator-driven studies to ensure that we're providing physicians with all the data they need to optimally treat their patients. So a very exciting program as we move into frontline.

Yes, I would just add what an incredible opportunity we have at talking about $5 billion in terms of fit, unfit, newly diagnosed patients and then obviously, what we've created in relapsed/refractory diseases, and what I would say is now a quite derisked situation for all of these combinations with data that we've generated. Great position.

Very exciting for sure. One thing is for the frontline Phase III trials, it seems like surrogate endpoint right now could be -- could use CR or MRD-negative CR as surrogate endpoints for approval. So I'm curious, have you got buy-in from the FDA on that? And if you're using MRD-negative CR as a surrogate endpoint, what's the right time line we should expect in terms of data readout?

Nick, do you want to talk about...

Yes, absolutely. And again, we're very proud of Syndax in terms of the number of firsts we've had and the leadership we've provided in the menin space. We're still the only approved menin inhibitor with a very, very broad indication. We were the first company to randomize the patient to frontline newly diagnosed. And we want to continue that journey of scientific leadership. So part of that is around innovating around novel endpoints. So we have -- and again, I'll maybe start with the unfit population in ven/aza. Complete response rate is a relatively accepted surrogate endpoint for accelerated approval in that setting. We have complete response rate built into the study we're doing with HOVON. It's called EVOLVE-2 study started enrolling earlier this year. We have CR built in as a dual primary endpoint. And based on the data we have generated to date from Beat AML and other sources, we have a high degree of confidence that we should be able to show an improvement over ven/aza alone for complete response rate that would support an accelerated approval. Now we haven't guided specifically around time lines other than to say the study is enrolling. HOVON provides an incredible international network of sites. We're going to have over 200 sites to enroll into that study, including sites adding it to the U.S. R&D and having sites enrolling in the U.S. And we can get to a CR measurement relatively soon because you don't need too much follow-up in order to be able to assess complete response rate. So that gives us a high degree of confidence that we should be able to enroll and have that study readout for CR quite soon to get an indication in the frontline setting. So that's for the unfit population. For the fit population, we're doing a lot of work with health authorities and academic groups to support an MRD-negative CR. We're focusing on an assessment based on a bone marrow. We think that's the most rigorous and the most sensitive way to assess a surrogate endpoint. And again, we're optimistic that in time and in the duration of that study, that would also support an accelerated approval if we were able to show a significant improvement over what you would consider historical rate, which is maybe of the order of somewhere around 40%, 45%. So that's how we're thinking about it. A lot of innovation built into those studies. They're very well-designed studies. We feel very optimistic that we can be first to both enroll and read out those studies because of the way they've been designed and set up.

Yes. Tell us a little more about that HOVON collaboration that you have. How do you think that you're able to kind of expedite the trial progress, have more patient enrolled more like more patients, we get to the right kind of number of events or MRD negative. Just tell us a little more about how you're thinking about using HOVON as a network to help the whole...

I mean this is a great group. We have collaborated with them incredibly closely. This is a group of some of the top thought leaders on the steering committee leading the design of this study and then a big network of sites. There are 2 considerations when you think about the execution of the Phase III. Obviously, speed is critical, and we're laser-focused on speed, and we think it will enroll very quickly. As I said, we're going to add the study onto the U.S. IND and have sites enrolling in the U.S., and I think that will really increase enrollment as well. So speed is paramount. And our expectation because of the way we've designed the study is that it will be first. But you mustn't forget quality. this is acute myeloid leukemia. And when you have an add-on therapy to a combination like ven/aza, you need to make sure that the patients are being really well managed and that the study is being conducted and executed in the best possible way. I feel extremely confident working with HOVON that we have the best scientific expertise advising us on the design of the study, how to get the standards of care, how to manage the toxicity of a triplet and ensure that the patients are being given the best possible chance to show the benefits of the drug. So I think it's both speed and quality. And the way the study is designed and with the endpoints we've built in and with the support and the collaboration of the health authorities that we've had along the journey all the way, we feel really confident that we can continue to lead in that space.

Got it. Yes. And just a follow-up on that one. I mean, it seems like a lot of competitors also going after frontline Phase III trials, Kura as well as Johnson & Johnson. So how do you plan to stay ahead of the curve? How do you -- how do you plan to stay ahead in terms of clinical development?

For FLT3 specifically or in general? In general. Well, so I mean, I think it speaks to a lot of it. I mean we have -- as I've spoken about HER1, let me just focus a little bit on FLT and intensive chemotherapy. So we're working -- we have a very well-designed study again, and there are some nuances in the study design that I won't go specifically into today because I don't want to talk about the details of the statistical analysis plan, but we feel extremely confident in the design of the study. We are working with an international CRO that we think gives us enormous leverage to enroll patients throughout the world. So it will be an internationally run study. A lot of centers recruiting outside the U.S., of course, some inside the U.S. And we think that the combination of the collaboration that we have, the experience and the knowledge of Revuforj in the market, being the only approved menin inhibitor, the breadth of the program that we have, the breadth of the indications and our laser focus on execution is going to position us very competitively. And our strong expectation and ambition is to lead and be first in the frontline setting. And I think that we feel quite confident about that just because we've led throughout, and we were off to the quickest start. And you'll see from the data we're going to -- we have already presented in the abstracts that the data we'll be following up with at ASH that our data look really quite compelling, which I think will really encourage physicians to want to enroll into the studies, and we're going to have very good momentum. So more on that to come.

Great. Yes. Great. And let's switch gears, talk a little bit more about Niktimvo. So launch, of course, has been off to a very strong start. What have you seen in terms of adoption so far? What are some of the trends that you can share with us?

Trends are very positive. I mean the product has did -- almost $46 million in the second full quarter. It's profitable. It's been profitable since the first quarter overall and also to Syndax. So it's a big driver of value. And there is an analog in this space, REZUROCK, which is a product that has third-line GVHD indication as well. We're pacing very well with REZUROCK, maybe exceeding that. So we feel like it's probably a low watermark for what we can do, and that product is doing $550 million in its third year of sales. So we're off to a fantastic start, new patient starts. Patients staying on drug, they get to response very quickly. And since launch, about 80% of patients are still on therapy. So that is actually a very good indicator of future growth as you start to stack patients on therapy month after month. So this is a really good early indicator of success. The broad adoption across transplant centers, people who are writing the therapy. I think we're in every single center across the country, multiple users using it multiple times. So there's great adoption. So all of the early measures of success are there as well as the fact that we're adding new patients every month. So I think last quarter, we added about 400 patients to therapy. So lots of repeat users, patients staying on, centers are adopting it. Payer coverage is very, very deep, almost 100% at this point. So we're in a really great place with the launch of Niktimvo.

Can you remind us, what percentage of patients are currently treated with fourth line and above? And how -- what percentage of patients are treated essentially off-label in third line in GVHD?

Well correction. It's not off-label in third line. So it's third line plus indication. It is a new therapy. So the majority of our uptake has been in fourth line so far. Good news, drug works on these patients. So whether you're third line, fourth line doesn't seem to make a difference. We have great utilization and great efficacy. So the best of the category that they've seen. So this is driving the utilization. So right now, it's predominantly fourth line, although we are fast growing in third line as well and taking share from the competitor that I mentioned. So we are penetrating -- it's about 6,500 patients available in third line plus. So it's a sizable patient population, and we are just -- we just only penetrated a small portion of that. So we expect that to grow. And as I mentioned, we're doing combination work as well to bring it into earlier lines, which would avail a bigger patient population if we were to be indicated there of roughly in the order of 15,000 patients in the U.S. and Europe.

Got you. Got you. Great. And so right now, in terms of clinical development, you're moving Niktimvo into IPF, right? So curious about the progress of the trial so far. And could you share some expectations around the data readout next year.

A very important program for us that we're driving, Nick?

Yes, I'm excited about it. And there's a number of catalysts, I think, for Niktimvo moving into 2026 and beyond. I mean, obviously, the move into other lines of GVHD is really important as well, combinations with dexamethasone and Jakafi. But the IPF program is a really interesting catalyst and I think maybe a little bit underappreciated given the high unmet need that exists in idiopathic pulmonary fibrosis and frankly, the lack of really good standards of care. So when you think about the clinical unmet need, the drugs that are being approved now are considered available therapy, somewhat delay the reduction in forced vital capacity, which is the endpoint you look at in a fibrotic disease like this. They don't actually improve. They just kind of delay by about 40% maybe on an annualized rate, the decline in SVC. Given the mechanism of action of axatilimab, which is really somewhat unique, it's a CSF-1R antibody. It targets macrophages and reduces both fibrosis and inflammation. That's a very compelling mechanistic reason why it would be effective in IPF. We have also seen from our experience in AGAVE-201, very good activity in the pulmonary manifestations of GVHD and also interestingly, a subset, about 30 patients with a syndrome called bronchiolitis obliterans syndrome, where we saw improvements in FEV1 and also symptoms. So both preclinical and clinical data that gives us a lot of confidence in the Phase II MAXPIRe. We're anticipating enrolling that Phase II study. It's a very well-designed classical proof-of-concept study with an annualized FVC primary endpoint that would be very informative to any potential future Phase III that it could trigger, which we anticipate seeing data towards the latter part of next year. But given the paucity of available therapies, we really are hoping for and anticipating a step change, both in terms of the reduction in FVC deterioration and potentially even a disease-modifying effect. And that really would be a game changer in that setting where you could even see some patients improve in terms of their functional capacity and FVC reads. So we'll see what that data shows, but high degree of confidence and that could be a very important catalyst, not just in IPF, but potentially many other settings, again, leveraging the CSF-1R hypothesis, other settings where inflammation and fibrosis has a role. And there are many potential opportunities to look at. So we're looking forward to that readout.

Great. We're almost out of time. Maybe just one last question. So what are some of the near-term catalysts that we should be watching for over the next 12 to 18 months?

Yes. So there are many. I think across both programs, we think about clinical development, frontline trials are starting for Revuforj in combination. We think that, that will be an important driver of value over time, real-world data, other pieces of information that will come out at ASH should be a very data-rich time for us as we present how the drug can be utilized in a variety of combinations in different settings. Next year, we have Niktimvo reading out in IPF, which will be potentially a tremendous catalyst for the stock. And we'll potentially have the opportunity to get into, as Nick mentioned, SAVE and Beat AML as 2 important trials, potentially bringing that into guidelines in '26 could be a really nice move before we get to frontline formally with the label. So a lot to look forward to from a clinical development standpoint. I would also say sales, as we drive here, we have tremendous opportunity derisked across these populations now with first-mover advantage, attacking 2 different markets of $5 billion-plus opportunity. And we have a fantastic molecule -- 2 molecules to get there. Last point is very important. We've guided to stable expense base over the next couple of years as we drive to profitability. We have about $0.5 billion in cash, specifically $456 million in cash to get there. So we are in a very good position to execute, and we are laser-focused on creating value with these assets. So with that, I will conclude.

Great. Thank you so much, Mike and Steve and Nick. Really appreciate your time. Thank you.

Thank you, David. Thank you.

Thank you, David.