All right. Okay, thanks for joining. Good morning, everyone. I'm David Dunn, 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, Michael Metzger, Chief Executive Officer; Steve Kloster, Chief Commercial Officer; and Nick Botwood, Chief Medical Officer. Thank you, Michael, Steve, and Nick. Appreciate you joining us.
Yeah, thanks for having us, David. Always a pleasure to be here with you and the UBS team.
That's great. So in regards to that, you know, for someone who's new to this next story, could you, you know, give a, you know, quick overview of Syndax, you know, your lead programs, as well as any kind of overall company strategy?
Sure. First of all, thanks for the introduction. We, we're at a very exciting point with the company. Syndax is now a commercial stage company focused on oncology. We have two commercial stage assets, which we've developed from the very beginning all the way through, and now have launched in the last year. We've had gotten off to a fantastic start. Revumenib is our asset in AML and ALL for acute leukemia, first of its kind, first in testing class, menin inhibitor, selective menin inhibitor, first indicated for KMT2A acute leukemia, which is about 10% of the overall population of AML and ALL. Now, newly introduced and approved is NPM1, is another large sub-segment of the population in adult AML and pediatrics. That affects about 30%-35% of AML.
Now we have a very broad offering in adults and pediatrics: AML, ALL, KMT2A, and NPM1, roughly 40-50% of the population. It is a very large opportunity, about a $5 billion opportunity, which we are exploiting. And we have, you know, a fantastic—we are off to a fantastic start there. We will tell you more about that. Our second asset is Niktimba, which is for chronic GVHD., another first of its kind, CSF1R 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 have done so far, but we are just getting started. The company strategy is to develop products in oncology, and we have done that successfully now in these two—with these two products.
We are expanding them. We're moving quickly into front-line trials to bring them to newly diagnosed patients in combination with standard of care therapy. That goes for both assets. Beyond that, we'll look to move into additional indications for both of these assets, not only newly diagnosed patients, but for instance, with Niktimba, going into areas such as IPF for patients who have fibrotic disease of the lung. Much to discuss, but we're off to a great start and here to answer your questions.
That's wonderful. You know, very exciting, a lot of progress, and a lot of, you know, excitement happening over the next 12 months too. Maybe we'll start with Revumenib, of course, the lead program. It's, you know, almost a year into launch in the KMT2A space, and, you know, you just launched the NPM1. Maybe just help us understand some of the ramping, how's it going so far. Could you share with us patients, also physician feedback and experience on Revumenib so far?
Feedback has been fantastic. I mean, we had, again, for NPM1, second indication, we had the opportunity to get the drug into guidelines. We were able to, ahead of approval, which was 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. We got approval, which was a broad indication for relapsed refractory disease in both adults and pediatric patients. The feedback from physicians has been fantastic. They're eager to put their patients on. The drug is well tolerated and very efficacious. 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.
We're excited about this new indication because it extends the population and allows us to really do more with the drug. So far, so good. We're ramping quickly, and we expect to have, you know, a good fourth quarter and into next year as well.
Excellent. Excellent. On KMT2A, right now, more than 750 patients have been treated so far.
Mm-hmm.
A third of them have progressed to transplantation. As you're treating more patients, you know, as you mentioned before, I mean, healthier patients, you can imagine, do you envision more patients would, you know, potentially, you know, 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. 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. We're talking about a year to two years potentially of maintenance, which is a very significant driver of this business, specifically for KMT2A patients who have the ability to, or their younger patient population, more of them are fit for chemotherapy and for transplant.
You bring them with Revuforj, you bring them back on maintenance, that could be, you know, potentially a very long period of time that drives the revenue of that, you know, 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. The ability to treat them earlier, patients tend to do better, stay on therapy longer, and potentially get maintenance as well. That is the paradigm that these physicians really would like to pursue. With a drug like Revuforj, they are able to do it as well as possible.
Got it. Got it. And so one thing you mentioned was that, you know, some patients were willing to maintenance therapy. And so far, we've seen about 30%-40% based on the most, most recent metric. About 30%-40% of patients were put back onto Revuforj after transplantation. How do you think this number will change over time? And what's your sort of expected percentage at steady state?
It should increase. Really, two factors. One is physician experience, the ability to, once they put a patient on maintenance, they tend to put them on maintenance again, right?
Mm-hmm.
They have a positive experience. We've heard that from physicians all along, that they expect to put their patients on maintenance as much as, you know, 70%-80% we expect potentially over time could go on maintenance. That's very different than 35%-40%. 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. You gotta give them a little bit of time. It takes three to four months once they have their transplant to engraft. Some of those patients are just starting to get to that period of time when they can go back on. The two factors are time and physician experience.
I think that favors a much higher, you know, amount of patients going back to maintenance.
Is there a number, you know, in terms of what the steady state maintenance therapy's gonna look like?
I said, you know, 70%-80% is a possibility. We don't know, based on our clinical experience, it's at least that high. We'll see. We'll see what happens. I do think that the building experience that we have should drive that number up meaningfully.
Got it. Okay. That's really good. And tell us a little bit more about, you know, those kind of patient journey around that. How quickly do you think these patients can be put on maintenance therapy based on this current experience with respect to patients, you know, getting on the CR and MRD negative CR and then, you know, transplantation and then eventually getting on maintenance? What's the right timeline look like here?
It's, right. The timeline 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 two months. Two to three months, 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. You have about three to four months of time where they're off Revuforj and they're pausing treatment, and then they return to maintenance thereafter. From start to resumption of therapy, it's somewhere in the six-month range where they'll start again.
Got it. Okay. 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.
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. I think physicians are getting more familiarity with how to dose. You have to remember that after transplant, you know, patients' marrows after engraftment are quite delicate. You have to have familiarity with dosing to ensure that the drug's tolerable. We're gaining a lot of experience now with managing Cytopenias. One of the benefits, I think, of Revumenib is that it does allow a little bit of flexibility in the dosing. Physicians are getting to know how to do that.
There's also some quite fascinating science in terms of, you know, 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 gonna, at ASH, have some quite interesting series of real-world evidence. You know, we've promised data coming from our commercial experience now every year of approved. 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 MD Anderson, interestingly from the pediatrics department of MD Anderson, that they also have experience in adults. In that series of about 10 patients that went on to get maintenance after transplant, we have a one-year event-free survival of 100%.
That is really encouraging for this pediatric population where normally the relapse rate would be quite high, that on maintenance, all of them tolerated it very well. Patients were able to dose interrupt or even reduce if necessary to manage cytopenias. To be seeing preliminary efficacy that looks as promising as it does, as those data continue to be generated, I think it is just going to increase the desire to have patients back on Revuforj after transplant. Already we are beginning to see that and publish on it. That is very exciting.
Yeah. I think another question just around the duration of therapy, I think most investors care about right now, just helps understand, you know, where is it now and how do you think it's gonna evolve, you know, after patients or more patients are getting onto maintenance therapy?
Yeah. What we've said is this first year of launch, we expect the duration of therapy in the order of four to six months. That factors in mostly new patients starting, patients staying on therapy and then dropping off and going to transplant. For a very small portion of the year, being able to come back. We expect that to accelerate in the future year. This year, factoring all that in, four to six months average time on therapy for this year. It extends next year with the introduction of more patients going to transplant, coming back from maintenance, probably more in the range of 6-12 months next year.
How do you think this 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, you know, 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 Revumenib that drives to remission so quickly and enables the transplant. I think this is a, you know, very, this population is specific for the KMT2A and NPM1 for a drug like Revumenib to really impact and drive maintenance in 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 Revumenib in NPM1 patients. You know, but we did see an updated black box warning of, you know, Torsades. It just helps understand the decision of the FDA to include, or to update the black box warning to include this Torsades case. And how do you think this might impact adoption in the NPM1 setting?
I'll just make one comment, and then I'll pass it to Nick. I don't think it'll 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 wanna 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 Revumenib. And they feel very, very comfortable with it. So our experience speaks for itself. I may well pass it to Nick specifically around NPM1.
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, you know, significant benefit that cause QT prolongation. 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 and 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. As we've expanded, we did identify a case of Torsades de Pointes that met the criteria for a warning. The guidance in terms of how you manage QT is exactly the same.
You do weekly ECG, you optimize electrolytes, and you make sure patients are well managed. By doing that, we've really been able to mitigate any potential risk of the clinical consequences of QT prolongation. That's really important for prescribing physicians. I think what's really driving use is efficacy in assessing where, for, you know, we're talking about relapse refractory AML. These patients have sadly very short life expectancy. What you wanna do is you wanna get these patients into response, give them a chance of a durable remission, and potentially even a transplant. That's very much in their minds.
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 relapse refractory AML. It is really very well managed and not a concern to prescribing physicians.
Yeah. I would just amplify the fact that this is an efficacy-driven market. Physicians care first and foremost about which drug is going to get their patients to remission. Our drug does a fantastic job of that. Relative to any other menin inhibitors potentially coming behind us, I do not think anybody has seen data that is reminiscent of what we have been able to show in monotherapy or even in combination. It makes the choice quite easy for physicians. They monitor the same way they were monitoring before. The label does not change that.
Gotcha. Got it. And since, you know, the approval, you had, you know, a couple of weeks, right, of, you know, bringing the field team, you know, with the updated label to physicians. I'm curious, you know, how has the feedback from physicians so far? You know, maybe Steve can maybe talk about this. You know, what has been some of the feedback from the physicians on the NPM1, especially on the NPM1 setting, on how they're viewing the label and how they're, you know, how they're treating patients so far on the ramp?
Yeah. Good, good question. There's a lot of excitement. We haven't had a lot of time yet to see any guidelines. We were granted in the third week of September. Little lift there, a little bit more visibility. Awareness is very high, certainly on the condition and certainly on the drug. You know, we talked about the KMT2A launch and the 750 patients that have been on since launch. There's been over 2,200 prescriptions. That's against an audience that's smaller than most other targeted AML therapies. It's off to a great start. The drug's done incredibly well. Physicians can easily identify patients. 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. There's no challenge, you know, no challenges to getting patients on therapy.
It's that same treating audience. You know, 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 gonna see NPM1 patients. That'll translate incredibly well. Early days, patient population, as we 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, maybe just add one thing that, you know, familiarity is so important, but also we know that physicians like to use the drug in different settings and in different combinations. You know, to support that, I mean, obviously we're done promoting that setting, but to support clinical practice, combinations of drugs is really important. You know, we're gonna have a really outstanding presence at ASH this year. We're excited about that. We're gonna have 12 abstracts for Revumenib, 23 if you include Niktimba. 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 Revumenib in combinations. That's their choice because they think it gives them a higher chance of getting a patient into response. You know, that's important.
Our focus has been ensuring that we're doing the right research, working with the best centers, with the best clinicians to generate data that supports how physicians wanna use Revuforj and generate that data. I think ASH is gonna be a testimony to how we're doing with that, more to come. You know, 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, you know, start talking about some of the combination strategies you have for Revuforj, especially moving to frontline. So maybe, you know, making just tell us a little more about some of the strategies and clinical compliance you have for Revuforj in combination with various different, you know, therapy standard of cares in frontline setting.
Yeah. I'm incredibly excited about that. I mean, as I said, we transform the standard of care in relapse 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. It's been a focus of our program throughout. We're gonna have some more very important data at ASH, you know, as we think about developing, you know, 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 forwards, and also, show preliminary efficacy.
If you start perhaps with the unfit population, patients not considered eligible for 7 plus 3 or intensive chemotherapy, that's really been a preliminary focus of our program. We have generated compelling data now from the Beat AML study. You will see some updated data at ASH from the SAFE study showing really compelling tolerability, but importantly, efficacy in combination with ven and an HMA, whether that's IV or oral. Those data give us and our collaborators a very high degree of confidence that we can get a successful phase three in combination with Venaza. We know that Venaza 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.
That's incredibly exciting for us because we've demonstrated such compelling data across NPM1 and KMT2A. When you think about intensive chemotherapy, patients fit for intensive chemotherapy, we're gonna update some important data at ASH showing our phase one 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 Revumenib, which is important. That's the dose we'd like to take forward into phase three, and we'll be confirming that shortly. Really importantly, compelling activity. We've seen 100% complete response rates in KMT2A and 100% MRD negativity.
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.
Mm-hmm.
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. That study's posted on ct.gov. In terms of the KMT2A population, more on that to come. We're very encouraged by the data we've seen, both in combination with intensive chemotherapy and Venclexta for that smaller population. We really think we're leading in that space because, again, we've seen 100% CR and 100% MRD negativity, which is extremely encouraging. Very robust plans to get us registration programs in the frontline. 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. Very exciting program as we move into frontline.
Yeah. Which is exciting. What an incredible opportunity we have at, you know, talking about $5 billion in terms, in terms of, you know, fit, unfit, newly diagnosed patients. And then obviously what we've created in relapse refractory disease in it, what I would say is now we've quite de-risked the situation, for all of these combinations with all the data that we've generated.
Great. Great position. Very exciting for sure. One thing is, you know, for the frontline phase three trials, it seems like a surrogate endpoint, you know, right now could be CR or MRD negative CR, a surrogate, a surrogate endpoint for approval. I'm curious, have you got buy-in from the FDA on that? And, you know, if you're using MRD, CR, MRD negative CR or CR as a surrogate endpoint, what sort of timeline we should expect in terms of, you know, data readout?
Sure. You wanna talk about that?
Yeah. Absolutely. You know, we're very proud at 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 a patient in the frontline newly diagnosed. We wanna continue that journey of scientific leadership. Part of that is around innovating around novel endpoints. We have, for, and again, I'll, you know, maybe start with the unfit population and Venclexta. 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 the Evolve 2 study, started enrolling earlier this year. We have CR built in as a dual primary endpoint.
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 Venclexta alone for complete response rate that would support an accelerated approval. We have not guided specifically around timelines, other than to say the study is enrolling. HOVON provides an incredible international network of sites. We are 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.. We can get to a CR measurement relatively soon because you do not need too much follow-up in order to be able to assess complete response rate.
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. That is 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, you know, a surrogate endpoint. 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 a historical rate, which is maybe of the order of somewhere around 40%-45%. That is 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.
Yeah. Tell us a little more about that HOVON collaboration, you know, that you have. You know, how do you think that you're able to kind of expedite that trial progress, you know, having more patient enrolled, more like, you know, have, you know, more patients, you know, that you get to the, you know, the right kind of 90 number events or MRD negatives? You know, just tell us a little more about how you're thinking about using HOVON, let's say, network to help expedite the whole clinical development.
I mean, this is a great group. You know, we've collaborated with them incredibly closely. This is a group of some of the top thought leaders on the steering committee and leading the design of this study and then a big network of sites. There were two considerations when you think about the execution of a phase three. Obviously, speed is critical, and we're laser-focused on speed, and we think it'll enroll very quickly. As I've said, we're gonna add the study onto the U.S. R&D and have sites enrolling in the US. I think that will really increase enrollment as well. Speed is paramount and our expectation because of the way we've designed the study is that it'll be first. You mustn't forget quality. You know, this is acute myeloid leukemia.
When you have an add-on therapy to a combination like Venclexta, 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 give 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.
I think it's both speed and quality, and the way the study's 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. Yeah. And just to follow up on that one, I mean, it seems like a lot of competitors also, you know, going after frontline phase three trials, you know, Cura as well as Johnson & Johnson. How do you plan to stay ahead of the curve? How do you stay, you know, how do you plan to stay ahead of them in terms of clinical development?
For flip three specifically or just in general?
Oh, in general. I mean, I think it speaks to a lot of it. I mean, we have, so I've spoken about HOVON. Let me just focus a little bit on fit and intensive chemotherapy.
Yeah. So we're working, you know, we have a very well-designed study again, and there are some, you know, nuances in the study design that we'll, I won't go in specifically into today because, you know, I don't wanna talk about the details of the statistical analysis plan, but we feel extremely confident in the design of the study. We're working with an international CRO that we think gives us enormous leverage to enroll patients throughout the world. It will be an internationally run study. A lot of centers recruiting outside the U.S., of course, some inside the U.S.
We think that the combination of the collaboration that we have, the experience and the knowledge of Revumenib 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 gonna position us very competitively. Our strong expectation and ambition is to lead and be first in the frontline setting. I think that we feel quite confident about that just because we've led throughout and we were off to the quickest start. You'll see from the data we have already presented in the abstracts, but the data will 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.
We're gonna have very good momentum. More, more on that to come.
Great. Great. Yeah. Great. Let's switch gears, talk a little bit more about the PIMPL. So launch, of course, has been off to a very strong start. What, what have you seen in terms of adoption so far? You know, what are some trends that you can share with us?
Trends are very positive. I mean, the product has, did 40, 40, almost $46 million. In the second full quarter, it's profitable. It's been profitable since the first quarter, overall. And also to FINDAC. So it's a big driver of value. There is an analog in the space, Rezurock, which is a product that has third line GVHD. indication as well. We're pacing very well with Rezurock, maybe exceeding that. We feel like it's probably a low watermark for what we can do. That product's doing $550 million in its third year of sale. 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.
That is actually a very good indicator of future growth as you start to stack patients on therapy month after month. This is a really good early indicator of success. You know, the broad adoption across transplant centers, people who are writing the therapy, I think we were in every single center across the country, multiple users using it multiple times. There is great adoption. All of the early measures of success are there, as well as the fact that, you know, we're adding new patients every month. I think last quarter, we added about 400 patients to therapy. Lots of repeat users, patients staying on, centers are adopting it. Payer coverage is very, very deep, almost 100% at this point. We're in a really great place with the launch of Niktimba.
To remind us, what percentage of patients are currently treated with fourth line and above? What percentage of patients are treated potentially off-label in third line, you know, GVHD.?
Correction. It's not off-label in third line.
Sorry.
It's third line plus indication. It is a new therapy. The majority of our uptake has been in fourth line so far. Good news. Drug works in, you know, in these patients. Whether you're third line, fourth line, doesn't seem to make a difference. We have great utilization and great efficacy. The best of the category that they've seen. This is driving the utilization. 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. We are, you know, penetrating, it's about 6,500 patients available in third line plus. It's a sizable patient population. We had just only penetrated a small portion of that. We expect that to grow.
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, roughly an order of 15,000 patients in the U.S. a year.
Gotcha. Gotcha. Great. And, and so, right now, in terms of, in terms of clinical development, you're moving Niktimba into IPF, right? So curious about the progress of the trial so far. And could you, you know, share some expectations around the data readout next year?
A very important program for us that we're driving, Nick?
Yeah. I'm excited about it. And, you know, there's a number of catalysts, I think, for Niktimba moving into 2026 and beyond. I mean, obviously, the move into earlier lines of GVHD. is really important as well, combinations with dexamethasone and Jakafi. The IPF programs are really interesting catalysts. 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. You know, so when you think about the clinical unmet need, you know, the drugs that are being approved now or are considered available therapies somewhat delay the reduction in forced vital capacity, which is the endpoint you look at in a fibrotic disease like this. They do not 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 CSF1R 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.. Also, interestingly, a subset, about 30 patients with a syndrome called bronchiolitis obliterans syndrome, where we saw improvements in FEV1 and also symptoms. Both preclinical and clinical data give us a lot of confidence in the phase two [MAXIMA]. We're anticipating enrolling that phase two study.
It's a very well-designed classical proof of concept study with an annualized SVC primary endpoint that would be very informative to any potential future phase three that it could trigger, which we anticipate seeing data towards the latter part of next year. You know, given the paucity of available therapies, we really are hoping for and anticipating a step change, both in terms of the reduction in SVC deterioration and potentially even a disease-modifying effect. 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 SVC reads.
We'll see what that data shows, but high degree of confidence in that could be a very important catalyst, not just in IPF, but potentially many other settings, again, leveraging this CSF1R hypothesis, you know, other settings where inflammation and fibrosis has a role. There were many potential opportunities to look at. We're looking forward to that readout.
Great. We are almost out of time. Just one last question. So what are some of the near-term catalysts that we should be watching for over the next 12-18 months?
Yeah. There are many. I think for 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 up. ASH should be a very data-rich time for us as we present how the drug can be utilized in a variety of combinations and different settings. Next year, we have Niktimvo reading out in IPF, which will be potentially a tremendous catalyst for the stock. We will potentially have the opportunity to get into, as Nick mentioned, SAVE and B-AML as two important trials, potentially bringing that into guidelines in 2026. Could be a really nice move before we get to frontline formally with a label. A lot to look forward to from a clinical development standpoint.
I would also say sales as we drive here, we have tremendous opportunity, de-risked across these populations now with first mover advantage, attacking two different markets of $5 billion-plus opportunity. We have a fantastic molecule, two molecules to get there. Last point is very important. We have guided to stable expense base over the next couple of years as we drive to profitability. We have about $500 million in cash, specifically $456 million in cash, to get there. We are in a very good position to execute, and we are laser-focused on creating value with these assets. I will conclude.
Great. Thank you so much, Mike and Steve and Nick. Really appreciate your time here.
Thank you, Darius.