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At Syndax . We've got a great program planned for you. I've got a couple of slides up front that I'll run through. We have some data that we'll be presenting. A couple of slides at the back, and then I'll present. I know all of you have a lot of questions. We have some KOL partners here today. That's a treat. When we get to the Q&A at the end, we'll ask you to hold questions till the end, and we certainly won't be offended if many of the questions are for our KOLs today. Certainly unique to have them here. So I mentioned it's exciting to be at ASH, and it's certainly exciting to be a part of Syndax. There's a whole lot that we've done as an organization over the last couple of years, and it's really culminated in this opportunity that we see before us.
Really unique and unprecedented for a company, regardless of size, to bring two products to market in roughly a 90-day window. I've been in this business for decades, and whether I've been at small, medium, or large-sized companies, it's truly incredible to bring products to market within that 90-day frame. Products that meet real unmet need, have great profiles, and really meet a lot of bars when we think about commercial potential. These are billion-dollar opportunities for both compounds. First, we'll talk about Revuforj. We're incredibly excited. Certainly, we'll roll out the data at ASH. As we know, this is a first-in-class, exciting opportunity. The product was approved on November 15th. We had drug in trade within a week, and it's currently being used commercially in market. Two things that I would keep in mind that we often talk about.
I mean, we're getting a lot of feedback here on the profile directly from physicians. They like what they see in the label. It's a drug they can use in a very wide patient population. They know how to use it. They know how to keep patients on it. That's incredibly important, and we believe the opportunity, we often talk about frontline and combo treatment, but the opportunity is right here before us, right in this first indication in KMT2A-r, relapsed refractory, acute leukemia, and that in and of itself is a big market, and there's no one there, and there's no one going to be in that space for at least two years or more if other products even get there. The second thing I would talk about is first-mover advantage. Often, it's something we talk about. That's not something that Syndax invented. That's just a market dynamic.
And the type of experience physicians are going to have with Revuforj, it's beginning now, learning how to use it, getting patients on it, managing through any reimbursement challenges that exist at launch, and ultimately getting the drug on formulary. It's hard to displace that. The market tells us that as other products make it to market, if they even get there, it's very difficult to replace that first mover. The other product that is certainly a focus at this meeting is Niktimvo. This is another exciting product, a product with a market with a lot of unmet need, A-grade profile. We know that this product was approved in—it was August 14th. The product will make it out to market in the early part of the first quarter of 2025. We've probably talked about this with all of you. It's just getting two new SKUs out.
We're actively engaged with FDA, and this product will be out in the early part of 2025. If you've had a chance to go to the Incyte booth, where Niktimvo is, remember, our partner, co-commercialization and co-development partner is Incyte. A lot of excitement around Niktimvo. There was a product theater. These are promotional talks. This was held on Saturday. Usually, you get 100- 200 folks attend these types of presentations. There were over 500 people there. And I think it really speaks to unmet need and speaks to what Niktimvo offers in the marketplace. In terms of ASH, if you think about the sequence of events really over the last six to, well, we'll say six weeks, first, the release of the NPM1 data, a little bit of an update here today. We had the product approval, and then we had ASH. Couldn't ask for better.
So if you've been to the Syndax booth, there's a picture here. Incredibly busy. We'll have over 2,000 folks already. There'll be more by the end of the meeting that have stopped by to talk about the product, to learn more about it, certainly to express interest. There are other activities. There's a product theater, as I mentioned, for Niktimvo. We had one for Revuforj that occurred on Sunday, also very well attended. We can talk about the menin session. Amazing, the interest in the space. I think all the benefit accrues to us, right, to Revuforj. It's the only product that's on the market, and it really, I think, will ultimately support the launch of the drug, both near-term and long-term. And the other benefit of being at a place like ASH, it's this. It's all of us meeting, and we take that same opportunity with clinicians.
So I've talked to dozens of clinicians here. We have a commercial footprint, med affairs, clinical development. So we've been taking advantage and leveraging the time we have at ASH, and we're getting great feedback on the drug. Folks are interested, who want to learn more about how to use it, and really excited to use it in their first patients. So what we're going to do now is we're going to shift over to the next part of our presentation that's going to be all about the data. Our first presentation is going to be led by our Chief Scientific Officer here at Syndax, Peter Ordentlich. He'll review the AGAVE-201 results, also give you a taste of what that IPF trial, the phase two trial, looks like.
Then we're lucky enough to have three outstanding KOLs that are here, not only well-renowned at their own institutions, but known nationally and even internationally. So I know you're going to get a ton of benefit from these presentations. First, we have Dr. Eytan Stein at Memorial Sloan Kettering Cancer Center in New York. He'll provide a leukemia overview and also give us an update on the relapsed refractory mutant NPM1 data from the AUGMENT-101 trial. That will be new data here. Then we have Dr. Ghayas Issa from MD Anderson Cancer Center in Houston. He'll review the relapsed refractory KMT2A AUGMENT-101 results. He'll also present the combination data from the SAVE trial. This was recently presented at ASH. And then finally, we have Dr.
Josh Zeidner from the University of North Carolina, and he will review the BEAT AML frontline combination trial results, which we know will be very exciting. So again, please enjoy the presentations from our physicians who are here and Peter. Hold questions, write them down, and I promise we'll get to as many of them as we can later. So Peter.
Good morning, everyone. So as Steve mentioned, I'll talk a little bit about the AGAVE-201 results, which we've presented in the past, focus in on a little bit of the data that was presented here at ASH, and then tie those into the IPF study that we have ongoing. So as you may recall, we conducted a randomized phase two pivotal study called the AGAVE-201 study. We've obviously published and read this out. It was published in New England Journal of Medicine a few months ago. It was actually the number one plenary presentation last year, and what that study did was test axatilimab in patients with chronic graft-versus-host disease that had progressed or did not respond to two prior systemic therapies.
And we tested three different doses there: 0.3 milligram per kilogram every two weeks, one milligram per kilogram every two weeks, and three milligram per kilogram every four weeks. And what we had shown was that, in fact, the highest response rate of 74% response was seen in the 0.3 milligram per kilogram every two weeks. And that was overall response rate anytime in the first six months. And a couple of the things that were noted, the time to response was quite rapid, around 1.7 months in median. We'll dig into that a little bit in the next couple of slides. And then also important is that the durability of the responses was quite good. 60% of patients maintained their response at over at least a year, if not over.
In fact, the data then that we showed for the 0.3 milligram per kilogram is what led to the recent approval of axatilimab. It's that dose and schedule that is the FDA-approved dose for now Niktimvo in these patients. One of the things that was notable were the demographics, the baseline demographics of the patients that were in our study as compared to some of the other pivotal studies that had been reported out for other agents, now standard of care within this third line plus setting. What we can see is that the patients that we treated were quite advanced in their chronic graft-versus-host disease. Median time since their diagnosis was about four years. Of note, the severity as measured by the NIH scoring system, 80% of the patients in our study were considered to have severe chronic graft-versus-host disease.
That's compared to about 60% in this pivotal study, the ROCKstar study for Rezurock. The median prior therapies was four. And what was really notable also here was that this was done at the time when some of these other agents became approved. And so patients in our study, in fact, had pretreatment often with all three, but you can see almost three quarters had prior ruxolitinib. That compares to about 30-something% for Rezurock, 31% prior ibrutinib, and 23% belumosudil. So it really does reflect the patient population that was treated with what we could consider to be a contemporary standard of care. So the data that was presented at ASH by Dr. Cho on Saturday as an oral presentation was actually quite interesting.
One of the things that investigators were really interested in was to try to look at time to response within each of the different organ systems. And this was a way to see if we could tease apart, were there organs that were responding faster or slower, and could we tease out some of the impact, for example, from anti-inflammatory or antifibrotic mechanism of action. And so to orient you, there's four bars. The first bar is at one month, then two months, three months, and six months. And that's the response rate within each organ at each of those time points. And so what we can see is that, in fact, as we showed previously, there's pretty rapid time to response across all organs, but there are some that respond with a median time to about a month to a month and a half.
Those are the ones on the left. And then there's a few that take a little bit longer, upwards to about three months, although you can see the range. Some of them take 10 months plus. But if we look at the ones that take a little bit longer, for example, lungs, eyes, skin, this probably reflects the fact that these have more fibrotic involvement. And so it may be expected to take a little bit longer. And the other thing that the presentation had, which was also interesting, was looking at symptom relief as recorded by the patients. That's using the modified Lee Symptom Scale. And when they looked at that analysis, it was shown that scoring by the symptom scale was much more rapid than the NIH scoring system used for the scoring of these responses.
So what that means, especially for the lungs, eyes, skin: patients were feeling better and reporting symptom improvement that were clinically meaningful even within the first month. So there is improvement seen with axatilimab early. It takes a little bit of time in some other organ systems. And so that was quite obviously nice to see. It's great for the patients to feel better after essentially one or two doses of axatilimab. So I obviously encourage you to look at the presentation for more data. But those were the main takeaways: the rapid time to response. Some organ systems take a little longer, and the patient symptoms occur quite rapidly. So that was in the pooled data, by the way. So this is with the 0.3 milligram per kilogram every two weeks cohort. And again, this is the responses by the organ systems.
What we're doing currently with our partner, for each of these organs, is a subgroup analysis, so a deeper dive into each of these. We'll be presenting our findings with each of these in upcoming scientific and clinical conferences. The first one that we focused on was lungs. We saw a quite good 47% response rate within lungs. We'll show you in a little bit the subgroup analysis. This, I think, reflects one of the harder-to-treat organ systems. It's important for us as we merge this into our work with IPF. This was a subgroup analysis data that was presented at the European Respiratory Society meeting in September. Obviously, there's a larger poster that accompanies this.
The nice thing in that, because we get a lot of questions, "Do we record PFTs as lung function measurements?" And the answer is yes. And so that presentation actually has the spider plots that we can see the PFT improvements for indicating lung function improvement in patients with severe bronchiolitis obliterans, which is the lung GVHD. And so on the left, the demographics of the patients are consistent with the overall patient population. You can see in the 0.3 milligram per kilogram, we had 32 patients that had lung involvement at baseline. And of these, 14, so we had no cutoff in terms of enrollment into the study. So any FEV1, which is a measurement of lung function, could be enrolled. 75% is the cutoff considered to have the BOS as a symptom.
And you can see almost half of the patients had a cutoff or less of FEV1 less than 39%. The reason that's interesting is the Rezurock, the ROCKstar study actually used that as a cutoff for eligibility. So they did not include any patients below that number, whereas about half of the ones that we have are below that. And you can see, again, a quarter of the patients have severe, the highest score for lung involvement based on the NIH scoring. And yet we still saw a 47% response rate in lungs. And so on the left, our symptom relief relative to how it's measured. So that's shortness of breath at baseline, both at rest and with exertion or exercise. And again, what you can see is that 92%, so all the patients that had measurements of shortness of breath at baseline at rest recorded an improvement in that.
The 0.3 milligram is the dark blue, and again, 62% recorded an improvement in the shortness of breath with exercise, so we can see the measurements in the lung function, but we can also see the actual benefit that patients are experiencing relative to axatilimab treatment in lungs, so with that, so we've been very interested in how do we expand and explore the benefits of axatilimab based on its anti-inflammatory and antifibrotic mechanism into other diseases where the role of CSF-1R blockade and monocytes/ macrophages are relevant, and we did quite a bit of work. We have robust preclinical data set. There's a number of publications that all support studying axatilimab in idiopathic pulmonary fibrosis. We obviously are leveraging also the findings we saw in both the AGAVE- 201, but also our previous phase one two study where we saw similar benefit in patients with lung involvement.
And so we started this study. It's a phase two randomized study, proof of concept for axatilimab in IPF. It's called the MaxPIRE study. And it's 135 patients randomized two to one to a standard of care plus axatilimab versus standard of care plus placebo. It has a 26-week endpoint, and the primary endpoint is change in FVC as a measure of lung function. The study is open and currently enrolling, and we hope to report top-line data in 2026. So that hopefully gives you a little bit of flavor of both the existing data, where we're looking to expand on axatilimab's benefit, and then the ongoing study that we have with IPF. So with that, I will turn it over to Dr. Stein to now dive into Revuforj. Thank you.
Okay. Thank you, Peter. I always love seeing data like that because I don't get to go to these sessions at ASH, so I get to learn about all these kinds of things here, so I'm going to give you a brief overview of acute leukemia, which many of you know already, so we'll keep it brief, and then I'm going to give you some of the updated data on revumenib in NPM1 mutant relapsed and refractory acute myeloid leukemia, so all of you will remember that the treatment paradigm for acute myeloid leukemia is that you give front-line treatment, and in general, for patients with intermediate or unfavorable risk disease or candidates for an allogeneic stem cell transplant, you try to get them transplanted. Many of those patients, especially with KMT2A, will end up relapsing and be refractory to treatment, which means they need other therapies.
For those patients fit for intensive chemotherapy, we typically give them intensive chemotherapy with seven plus three or FLAG-Ida or some other intensive regimen, followed by a consolidative allogeneic stem cell transplant or further rounds of intensive chemotherapy consolidation. For those patients unfit for intensive chemotherapy, we give the combination now of azacitidine and venetoclax typically, and when those patients end up relapsing, they need to get either salvage chemotherapy, which typically doesn't work very well, or they need to get some sort of targeted agent if they are lucky enough to have a target like a FLT3 or an IDH or a KMT2A rearrangement. This just shows you the general prevalence of KMT2A rearranged acute leukemia and NPM1 mutant acute leukemia. KMT2A rearranged acute leukemias account for approximately 10% of AML or acute lymphoblastic leukemia. Most of those patients are fit for intensive chemotherapy.
KMT2A tends to happen in younger patients, but about 20% of patients will be patients who will receive azacitidine and venetoclax, and then when you think about the group of patients who are relapsed or refractory, we estimate that's about 2,000 patients in the United States per year with relapsed and refractory KMT2A rearranged acute leukemia. NPM1 is much more common in acute myeloid leukemia than KMT2A. It occurs in 30% of newly diagnosed acute myeloid leukemia. 60% of those patients are fit for intensive chemotherapy. Approximately 30%-40% are unfit for intensive chemotherapy, and the number of patients who are relapsed or refractory ends up being about 3,000-4,500 patients per year with relapsed and refractory NPM1 mutations, so I want to remind you a little bit about the response criteria in AML. This is a little bit of a busy slide.
Last year, when I was here, I told you not to look at the slide and just to look at me. This year, you can look at the slide because it's more interesting than looking at me, and so here's what I want to remind you. All the response criteria in acute myeloid leukemia, except for a partial remission, which you don't need to think about, require the absence of blasts, meaning the blasts have to be less than 5% in the bone marrow. What we call an MLFS or a CR or a CRh or a CRi depends on the degree of recovery of the peripheral blood counts, specifically the neutrophils and the platelets, so if you have a response, it means that you've got less than 5% blasts.
For us folks who treat acute myeloid leukemia and acute lymphoblastic leukemia, this is important because once you have less than 5% blasts, the transplanters are much more willing to take your patient to transplant. And maybe more importantly, that transplant is much more likely to be successful. So we don't necessarily wait for the patient to have a CR. In fact, we don't wait for the patient to have a true CR before they go on to an allogeneic, before we send them to an allogeneic stem cell transplant, because we want to get them to that transplant as soon as the blasts are less than 5%. And I think that explains, as you'll see later, the delta, or at least partially, the delta between the overall response rate and the CR/CRh rate you see in the Revuforj studies and in other studies.
That's because many of us just send our patients to transplant before the patient has a chance to achieve a true CR. This is to show you two things this slide. On the left-hand side, what I'm showing you is the evolution of responses actually with an IDH2 inhibitor in relapsed and refractory acute myeloid leukemia. To highlight the point that when you look at the blue bars that sort of become higher and higher and more frequent as you go from one week on enasidenib all the way to nine weeks on enasidenib, that is because differentiation agents take time to work. Initially, you will get a response. You'll get clearance of the blasts. Only afterwards, a month or two into therapy, whether you get that true complete remission or complete remission with partial hematologic recovery.
The time to response with a drug like revumenib may depend a little bit on what the mutation is. So the time to response is different actually in patients with KMT2A rearranged disease and patients with mutations in NPM1. I'll show you that in a second. And the duration of response is really, I think, influenced by a number of things. Two of them are the depth of response. So achieving a morphologic CR is better than achieving a partial remission where you still have blasts. And maybe more importantly, achieving an MRD negative CR where there's no evidence at all of any leukemic cells by our most sensitive methods likely leads to a longer duration of response than if you just have a morphologic CR. In addition, the ability to receive a transplant is an important factor.
Patients who go on to transplant and then could get maintenance therapy after transplant, they are more likely to have a prolonged duration of response than patients who cannot go on to an allogeneic stem cell transplant. So here are some of the data that we presented on the call or Syndax presented on the investors' call a few weeks ago with one additional twist that I will whet your appetite with that you can get excited in the next few slides. So don't all jump up and get too excited. Just wait. Okay. So the dose escalation, as you know, was to define the recommended phase two dose of revumenib. And then there were two expansion cohorts in the phase two, KMT2A-rearranged and NPM1. You all know about the FDA approval.
Here are the baseline characteristics of the patients treated in the phase two cohort with relapsed refractory AML with an NPM1 mutation. Again, we defined a safety population, and then a protocol-defined efficacy population. This is what was presented on the investor call. The safety population is 84 patients. The protocol-defined efficacy population is 64 patients. You can see the median age is 65 years old in the adult-defined efficacy population. The other things of interest here is that 34% of the patients have a FLT3 internal tandem duplication with their NPM1. 6% have a FLT3 tyrosine kinase domain mutation with their NPM1. Some patients have IDH1 and IDH2 mutations. You can see these patients are primarily what are called refractory relapse, meaning they were unresponsive to their most recent salvage treatment. A huge number of these patients had received prior venetoclax as part of their treatment regimen, 75%.
And a little bit less than a quarter of the patients had relapsed after an allogeneic stem cell transplant. So again, what we showed a few weeks ago, the combined rate of CR and CRh in the 64 patients who were defined as efficacy evaluation eligible was 23%. 19% of patients achieved a CR. 5% achieved a CRh. And of those patients who achieved a CR or CRh, 64% were MRD negative. I say this all the time, but that's very, very impressive for a single agent in relapsed and refractory acute myeloid leukemia as a targeted therapy. If you look at IDH inhibitor therapy as a targeted therapy, the MRD negative rate for the IDH mutations is in the range of 20%- 30%. The overall response rate is 47%. Again, you're seeing that delta I talked about between the overall response rate and the rate of CR/CRh.
And then what we call the composite complete remission rate, which is the complete remission rate that is CR/CRh, CRi, CRp, those patients, the composite complete remission rate is 30%. And three out of five patients were able to resume Revuforj post-transplant. Now, this is a little bit of updated data with a post-hoc efficacy evaluable population. So this includes an additional 13 patients on top of the 64 patients that we just talked about. So these are 77 patients now because more patients became efficacy evaluable since we spoke a few weeks ago. So in this updated data set, the rate of CR and CRh is slightly higher at 26%, with a CR rate of 21%, a CRh rate of 5%. And the MRD negative CR/CRh rate is 63%, with a median duration of CR/CRh of 4.7 months, which is similar to what we showed previously.
Just to go back and repeat that, in this earlier data set with 64 patients, CR/CRh rate of 23%, overall response rate of 47%. In the slightly updated data set of 77 patients, CR/CRh rate of 26%, with an overall response rate of 48%. This just is the swimmers' plot, which we're not going to go through. We'll go through the table on the right-hand side where you can see the median time to CR/CRh is 2.76 months, and the median duration of CR/CRh is 4.7 months. This is what I was describing earlier, where with KMT2A, if you look at the FDA label, if I'm remembering this correctly, the median time to CR/CRh is 1.9 months. I see the Syndax people nodding their heads and back, so I got it right. Over here with NPM1, the CR/CRh rate, median time to CR/CRh is 2.76 months.
So an NPM1 mutant patient needs to stay on this menin inhibitor longer in order to achieve a true CR/CRh. Similarly, the median time to the first response, whatever that response might be, whether it's a morphologic leukemia-free state, a CRi, whatever you call it, is a little bit longer at 1.84 months. This is a forest plot looking at different subgroups and what the responses are across different subgroups in patients with NPM1 mutations. It breaks it down in a variety of different ways. These slides obviously will be available for you to spend a lot of time looking at in your spare time. I think the important things to highlight here is that it did not matter the number of prior lines of therapy in terms of responses.
Whether a patient had received prior venetoclax or had not received prior venetoclax, those patients still all ended up responding at around the same rate as the other patients. What about the safety results? This looks at the treatment-related adverse events in the safety population of 84 patients. The rate of QT prolongation, and this is grade 3 or higher treatment-related adverse events, the rate of QT prolongation was 21%, with 19% of those patients having grade 3 QT prolongation and 2% of patients having grade 4 QT prolongation. There were no grade 5 events when it came to QT prolongation. differentiation syndrome of grade 3 or higher was seen in 13% of patients, 11% grade 3, 2% grade 4. The other things on this slide, I think, are not particularly relevant. There's a little bit of cytopenias that have been attributed to the drug.
So just to make, before I turn it over to Ghayas, just to make a few comments just on the safety profile. I get a lot of questions about the QT prolongation. I think that it's important to note that in clinical practice, I really don't spend a lot of time thinking about QT prolongation. I do think about being sure my patients' potassium is four or above or magnesium is two or above, but I would never not use any drug for relapsed and refractory acute myeloid leukemia because of a QT prolongation issue. You just check the EKGs. The Revuforj label I actually think is very reasonable in that you check those EKGs before you start. You check it weekly for four weeks and then monthly afterwards.
That's not a big lift for a patient who's coming in usually two to three times a week for blood checks and blood transfusions. It's not a big lift for the doctor because I just say, "Go get an EKG." Someone does an EKG and puts it in front of me, and I look at it, and it takes about 30 seconds. So that's about it. I'm going to now give it over to Dr. Issa, who's going to talk about KMT2A in relapsed refractory setting and the SAVE results. Thank you. It is notable that only the Syndax people clap.
Hi, everyone. Okay. I'm going to talk to you specifically about the KMT2A cohort results. These are from the phase two, and I'll take you through the combinations. So KMT2A rearranged leukemias are difficult to treat, and that's because they're resistant to the conventional chemotherapies that we have.
When they're newly diagnosed, they tend to respond less than other leukemias, and when they're relapsed, their outcomes are much worse, and this is data that we have done at MD Anderson to give you a historical perspective on what would have happened to patients if they didn't have menin inhibitors, and the outcomes are really bad. I would say in KMT2A, the median overall survival is about 2.4 months, so in other terms, when we first started studying revumenib for KMT2A, patients were given the options of hospice or clinical trial, and the first few brave ones joined the clinical trial, and because they responded, we had more and more patients get on this study, and so before revumenib, there had been no approved targeted therapies for KMT2A rearranged leukemias, so this is a timeline of the trial and the various analyses that we've done.
The phase one, around March 2022, there was a presentation, and then we did the phase two interim analysis, and this is the data that supported the label. So as part of the study design, there was an interim analysis that allowed a look at the primary endpoint, which was the rate of CR/CRh. And because the trial met the primary endpoint, we used this data for submitting for regulatory approval. But obviously, patients could have met that primary endpoint after that interim analysis because it was just like Eytan was showing, some patients would take longer to respond, and there had been updated results since. And I'll take you through some of those data. So safety evaluable patients are, in general, any patient who had one dose of revumenib, and efficacy evaluable depends on presence of KMT2A and whether they had enough time to get the assessment.
These are the numbers that you see. This is the most updated results. The efficacy evaluable population is 97. The safety evaluable population is 116. This is by far the biggest sample size for KMT2A evaluated across any targeted therapy, any therapy, I think, for leukemia, for adult leukemia or pediatric leukemia. The age is lower than what you've seen with NPM1. That's because KMT2A really happens in children, infants, and adults, but it's distributed across the age. There's a higher preponderance a little bit in younger patients, slightly more females, and that's probably because of the therapy-related nature of KMT2A rearranged leukemias. KMT2A could happen as an effect of chemotherapy given for other cancers. Women that have breast cancer or have lymphomas would have a higher risk of KMT2A rearranged leukemias. That's why we may see an imbalance of female to male.
This is the distribution, the race distribution of patients enrolled mostly in the United States. KMT2A is most common in acute myeloid leukemia. That's why you see AML at the top. Then a few patients were treated with acute lymphoblastic leukemia, and the label supports use of Revuforj in AML. That's because we saw also responses in AML. The co-mutations are lower in KMT2A. KMT2A is a very potent driver. It is enough to cause leukemia with less co-mutations. But if there are co-mutations, the common ones are FLT3, for example, and RAS. These patients were heavily pretreated. About 70% had prior venetoclax, about half had relapsed after a stem cell transplant. There are a few I know of because I've treated them that had relapsed after two stem cell transplants and got on the study. This is the summary of the response.
So the overall response rate, just like Eytan was talking about, so any blasts less than 5% is 63.9%. This is the highest response rate in KMT2A. And I know that for a fact because I've tabulated all menin inhibitor responses. There could be sometimes different responses because of smaller cohorts. If you believe in robustness, sample size, consistent results, it's the highest response rate seen in KMT2A rearranged leukemias. The CR/CRh rate is 23%. The MRD negative rate, especially in those that had CR/CRh, was 61%. And you can see the distribution of count recovery responses, so CR/CRh or CRi in these patients. The median duration of response was 6.4 months. This is based on the results that were at the interim analysis.
But since then, since we had additional patients, 13 patients that had met the primary endpoint CR/CRh, and beyond that, their duration of response is 13 months. A lot of these patients went to transplant. This is what you're going to see in this swimmers' plot. So there's a break in the swim lanes that you see. This is the time to transplant, and then the shade starts again. That means these patients restarted maintenance post-transplant. The blue is the adult population. The green is the pediatric population. The take-home message is that this therapy allowed many patients that had no other options to get to a curative intent transplant. And all of them are still alive because of this therapy, because they were able to get the transplant and then resume maintenance too. And the goal of maintenance is to prevent leukemia. That's an important also point to highlight.
I can't remember if we went through why we do maintenance. Transplant is great and curative, but transplant takes time. The effect of transplant, which is called graft versus leukemia effect, doesn't kick in immediately, like the day you start to transplant. The goal of maintenance therapies is to reduce the burden as much as possible because transplant works better with small amounts of leukemia, delay leukemia until the GVL kicks in. I get asked this question sometimes about what makes people live longer after getting Revuforj on study. I think it's lower burden before transplant. This is a drug that is driving very low MRD negative remissions before transplant. Maybe some postulation about improving graft versus leukemia effect. There's some data on menin inhibitors that improve expression of antigens that are critical for T cells to kill leukemia.
That's something that hopefully we're going to study soon post-transplant. The whole summary is that that's why physicians would try to start maintenance post-transplant in these medicines, especially with Revuforj, where we have a lot of experience with it. Overall, about 33% of patients went to transplant in any response. 40% of those that had CR/CRh went to transplant. This goes back to the point that Eytan was mentioning, and that's because we don't necessarily wait for count recovery to get them to transplant. We want the lowest burden possible to get them to transplant regardless of just improving the numbers. About half of the patients that went to transplant restarted Revuforj post-transplant. This is a summary of the safety.
If you look at treatment emergent adverse events, this is any adverse event that's recorded while on study, regardless of whether it's related to the drug or not. This is consistent with what we see with patients that have leukemia that are generally sick. But if you look at adverse events that led to dose reduction or discontinuation, the rates of adverse events that led to that were low in general, with very few deaths related to treatments. This is a summary of all the adverse events. I can tell you, this is a busy slide. I can tell you what I tell my patients before I consent them.
So the things that I look at are differentiation syndrome, which is a class effect of menin inhibitors, QT prolongation because we monitor it, and I tell the patients about the EKGs that we're going to do, and then maybe the risk of infection and bleeding because it's a common side effect in any leukemia we treat. Otherwise, this is by far better than any chemotherapy I could give to patients. And the moment the patients start on study, they understand what I meant by that. This is a pill that they take twice a day. It's very different than what they have. If you look at the summary, you may see nausea at 44%. So some patients have nausea, but in the overwhelming majority, this is a low-grade nausea. So it's usually anti-nausea medication that helps with it. Otherwise, minimal side effects.
The differentiation syndrome in here, grade 3, was about 14%, and the QT prolongation grade 3 was about 10%. We didn't see any new safety signals compared to the phase one results, and no patients discontinued Revuforj because of cytopenias, differentiation syndrome, or QT prolongation. This is the summary specifically of the adverse events and differentiation syndrome or QT prolongation and a breakdown of the dose interruption or dose reduction. You can also see the time to onset. So in general, differentiation syndrome happens within a week or two weeks. In the overwhelming majority of cases, one dose of steroids and the patients feel much better. It's almost used as a diagnostic tool in DS where patients would feel better when we start the steroids, and then we continue the steroids for a week and they feel better.
The QT prolongation just requires reduction in the dose, and that usually takes care of it if it's grade 3. This is my patient, and this is a patient treated on SAVE, which I'm going to talk about next. This is someone who's 74, and he has a very refractory NPM1 mutant acute leukemia. He had RAS, PTPN11, FLT3 mutations. He was treated with every standard therapy that we've used. Seven plus three is the standard chemotherapy plus a FLT3 inhibitor, midostaurin. Then he had high-dose cytarabine and gemtuzumab, which is an antibody-drug conjugate against CD33. Then he had azacitidine and had no response. This is the critical point, I think. He had already azacitidine and did not respond. Then he enrolled on SAVE, which is a different formulation of AZA or azacitidine, another hypomethylating agent, venetoclax and revumenib.
So the heavy lifting is done by Revuforj when this patient got on study. And you can see the skin lesions improving within a month of treatment on SAVE. And this patient, if you look at the SAVE data, was called a non-response. And that's because, unlike I always joke, if this was pancreatic cancer, it would be a New England Journal, because in solid tumors, they don't have the luxury of therapies that we have that reduce the disease burden significantly. So in the solid tumor world, this would be called a partial response, I think, or something like that. In leukemia, responses are more strict. So there has to be full resolution of any extramedullary disease for it to be called a response. Because he didn't have full resolution, this would be a non-responder.
In other words, some patients get clinical benefit even though they may not meet the strict criteria of response, and this is one of them. In summary, for KMT2A rearranged single-agent activity, Revuforj is the first approved menin inhibitor for KMT2A rearranged leukemias. This is also the largest sample size and the most robust data set that I know of that shows responses. This is, again, almost similar responses in phase one results, interim analysis of phase two, updated analysis of phase two. No matter how we're looking at it, we have an overall response rate of about 60% and a CR/CRh rate between 21%-30%. To me, that's really promising. Okay, I'll take you through the results of SAVE. This used to make more sense when Revuforj was called SNDX-5613.
It's an abbreviation of Syndax, Astex, which is oral decitabine, and venetoclax. This is for acute myeloid leukemia. The reason why we use this combination is because hypomethylating agent and venetoclax is a standard in acute myeloid leukemia. It is the standard for older patients that cannot get high-intensity chemo. We also use this regimen sometimes as salvage, meaning patients that have refractory leukemia, even though the outcomes are not great. There is a reason to combine with HMA and VEN. That is just practical. There's also a good scientific reason to combine venetoclax and menin inhibition. KMT2A or NPM1 have high levels of BCL-2, which is the target of venetoclax, so they respond to venetoclax. If you look at preclinical models, when you combine a menin inhibitor and BCL-2, it eradicates the stem cells and the progenitor cells.
It has the capacity of reducing leukemia burden much more than any of the single medicines, venetoclax alone or Revuforj alone. And that's, you can see in the mouse model study at the bottom, that's why there was extension and survival in these mice in combination with Revuforj and venetoclax. And this data is also very robust. Any menin inhibitor with venetoclax in mouse models has shown the same results. I think it's really promising about the effect of menin plus venetoclax. For those reasons, we designed SAVE, which is a phase one/two study. We used a three plus three design for dose escalation, which is a standard method to decide on a dose in phase one. Patients on SAVE were age 12 and above. That's following the FDA guidance.
Whenever we don't need to adjust pills by body size or mass or age, you could do 12 and above. And a lot of the younger patients, 12- 18, may have KMT2A or NUP98. An important distinction on SAVE versus other studies that have venetoclax is that we chose 14 days of venetoclax. And that's because when I was designing the study, I had a lot of confidence in this combination. We had a lot of data from other triplets that we study at MD Anderson, where 14 days of venetoclax are sufficient if you add a good targeted agent to get your responses. We used the same doses that we used with revumenib adjusted to CYP3A4. And on this study, we did maintenance revumenib post-transplant for one year. This is the baseline characteristics of the patients that have been treated so far or at the time of ASH.
There are 33 patients, 49%, so 16 have KMT2A, 36% have NPM1, and 15% have NUP98. We haven't talked a lot about NUP98. I would compare it to. I would almost call it like the more resistant cousin of KMT2A. It has the same dependency on menin KMT2A, but they tend to, well, not respond to anything else. For menin inhibitors, they tend to respond with some residual disease, and I'll take you through this data. The co-mutations are FLT3, 30%, WT1 or RAS. This is a reflection of these patients. These patients enrolled on SAVE were heavily pretreated, three prior lines of therapy. Important to note, 60% had already progressed on a venetoclax-based regimen. All the patients that had a FLT3 inhibitor had a prior FLT3 inhibitor, and about 36% had a prior transplant. We saw a dose-limiting toxicity, which is a drop in the platelet count.
But that also is related to how the study was designed. So at that time, we adjusted how we give Revuforj. So when we hold Revuforj, the counts recovered. And after that, we didn't see any additional toxicities, and we proceeded to phase two. We chose the same dose as monotherapy on SAVE, which is 163 plus azoles as the recommended phase two dose. This is the disposition of patients. This is almost like a snapshot. At time of ASH, what was the condition of these patients? So 40% had been still on study. Two had completed the study, including maintenance. And among those that went to transplant, 40% were able to get to transplant, which is a relatively high number that tells you about how well this therapy was able to get remission to get them to transplant.
Half of those that went to transplant were able to restart maintenance. Then you have a list of all the reasons why patients came off study. This is a summary of the adverse events on SAVE. The most common side effect was QT prolongation, but this is of any grade. If you look at grade three or higher QT prolongation, the rate was about 9%. This is similar to what we've seen on monotherapy. Another important distinction is differentiation syndrome. So overall, we saw on the combination less differentiation syndrome and less severe differentiation syndrome. This was not surprising to us because we've learned that from other leukemias. So acute promyelocytic leukemia, when we used each of the agents alone, there was a higher chance of DS. When those agents were combined with chemo, the chance of DS was lower. Same with IDH, where when Dr.
Stein was doing these studies. There was DS with single agent, much less differentiation syndrome with chemo. This is what we're seeing in this case too. This is the summary of the responses. Overall, SAVE led to a high response rate. The overall response rate is 82%. I can tell you that it's probably going to be higher because I know the patients that you see below the six, no response, not evaluable. Four were not evaluable, and I've gotten those results last week, and they're in remission too. The proportion of patients who are responding are going to be higher. The CR/CRh rate was 48%. You can see the same response across these genotypes, except for the MRD negative responses were really high. Among patients with CR/CRh, the KMT2A or an NPM1, the MRD negative rate was 100%.
The main struggle we have is with NUP98, where there is a response and the MRD negative rate is less, and I think it may also be another issue where it's time to response. It may just take longer for NUP98 patients to respond to menin inhibition, and this is, again, the breakdown of patients that went to transplant. This is a swimmer's plot. You guys have seen many versions of this, but just to guide you through it, the shades reflect the different phases on the study, so the blue would be when they got the combination. The lighter blue shade is when they were going to transplant, and the purple is when they started maintenance. The top two patients are patients that completed treatment.
The first one is an 18-year-old who finished high school, and she wants to be a nurse practitioner in transplant because she was so happy with her team after doing transplant, and the second one is a 12-year-old that also completed treatment and went back to school. When we look at those that progressed, there was no clear difference in their mutations, except one patient that had a FLT3 increase and a phenotype shift in NUP98. This is something really rare. The median follow-up was about nine months, and the time to response was quick within the first cycle. This is at the time of the ASH presentation, the median duration of CR/CRh, which is not reached, 74% had, and the median follow-up is nine months, 74% at six months, and the median overall survival was not reached, and a six-month OS of 68%.
When we look at all the subtypes, so these are small subsets of this patient population, but if you try to address questions on whether there are particular characteristics that make patients more likely to respond or not, we didn't see any. Importantly, how the genotype, for example, KMT2A or NPM1, the chances of CR/CRh were the same. The number of therapies that they've had in the past, the chances of response were the same. Or if they've had prior venetoclax, the chances of CR/CRh was the same. So in summary, this is an all-pill combination that is showing great response rates. So 82% overall response rate, 48% CR/CRh, and the median duration of response is not reached. We see less differentiation syndrome. We see some myelosuppression, but I have data from MD Anderson of the ASTX and VEN alone study.
The chances of complications of myelosuppression, such as severe neutropenia or thrombocytopenia or things like that, are similar to what we expect with hypomethylating agent and venetoclax. This study is now accruing newly diagnosed patients. I'll present this data when we have more patients in a future meeting. I'll pass it on to Josh. Thank you.
All right. Good morning, everyone. We've heard such exciting data in the relapsed refractory setting. I'm going to walk you through some of the exciting data that we have in the frontline space. Now we're going to be talking about unfit. Do I have a point? It's working. We're going to be talking about unfit patients for intensive chemotherapy.
And just to walk you all through some of the existing data that we have with our standard frontline regimen of azacitidine and venetoclax, I think it's important to understand the context of Aza/Ven in this patient population. So this is the obligatory slide from the VIALE-A study showing the results of Aza/Ven versus azacitidine and placebo. And you can see median survival of Aza/Ven, 15 months, but complete remission rates, as Dr. Stein kind of went through, requires full hematologic recovery. ANC above 1,000, neutrophil count above 1,000, platelet count above 100,000, 37% with Aza/Ven, composite CR rate, 66%. And less than half of these patients achieved a composite remission within the first cycle of therapy. Long-term outcomes, however, despite median survival being 15 months with Aza/Ven, is still quite poor. This is still an unmet need here. Two-year survival, less than 40%.
The majority of these patients will unfortunately relapse. We've heard about NPM1 mutations being the most common overall mutation in AML. About 30% of newly diagnosed AML patients will have an NPM1 mutation. It turns out that when you look at the VIALE-A subset data, Aza/Ven versus azacitidine and placebo, and again, this is in newly diagnosed unfit patients, either over the age of 75 or less than 75 years old, but with conditions that render them unfit for intensive chemotherapy, there was no significant survival advantage with Aza/Ven over azacitidine and placebo in the NPM1 mutated cohort. We think of this subgroup as being a favorable risk subgroup, but I think the reason we really have not seen a survival advantage with Aza/Ven overall in an NPM1 mutated cohort is that about half of these patients will have a signaling mutation.
And we call these signaling mutations either with a FLT3-ITD, NRAS, or KRAS. And it turns out that Aza/Ven is much less effective in patients with these signaling mutations, and about half of NPM1 mutations will have a concomitant signaling mutation. You can see the survival is vastly different in NPM1 mutated patients with and without a signaling mutation. So that really sets us up for the study that I'm fortunate to be leading through the Leukemia and Lymphoma Society. This is the BEAT AML study that we went over briefly last year, and I presented that at the European Hematology Association Congress in June. And just to kind of walk you through the study schema here, so this is for patients 60 years or over, unfit for intensive chemotherapy.
They had to have either an NPM1 mutation, and that was centrally collected, or local KMT2A rearrangement by cytogenetics or FISH. And these patients received standard azacitidine and venetoclax. venetoclax was given for 28-day consecutive cycles. And revumenib was initially dose-escalated in two different dose levels, and all these patients were on a concomitant strong CYP3A4 inhibitor. Dose level one was 113. Dose level two was 163 milligrams q12 hours. And patients would receive what we would call induction phase, one, two, or three cycles of therapy until they achieved a CR remission. And then once patients achieved a CR remission, they would continue the same triplet therapy until relapse or progression. And we actually did not reduce the doses of revumenib, azacitidine, or venetoclax in continuation phase unless there were toxicities or hematologic toxicities that required a dose reduction. So where we are with the current study.
This was the initial dose escalation. And we presented this data that we did not see any dose-limiting toxicities between dose level one or two. So we then expanded at dose level two, which was the 163 milligrams cohort, 13 additional patients. And then we wanted to get equal numbers of dose levels one and two to really compare both safety and activity. And so we had a dose expansion randomization. And since we wanted to get equal numbers, you can see that overall, we have very similar dose level one versus two, but the randomization was really skewed to dose level one to get these equal numbers. So we're at 43 patients in this combined expansion cohort. And we've now started a new randomized expansion cohort that's a little bit different where we want 20 additional patients, 10 in dose level one, 10 in dose level two.
But this cohort now will prohibit the use of strong CYP3A4 inhibitor azoles with the first cycle of therapy. So all these other patients here had a concomitant strong CYP3A4 inhibitor azole with their first cycle, and these patients will not have a strong CYP3A4 inhibitor azole. So this is the demographics here. And so we're including the 46 total patients. And again, that includes the three additional patients. This is an ongoing cohort now that we're enrolling as we speak. So total 46 patients enrolled. And when I previously reported this data at EHA, it was a 26-patient cohort, and we had 65% NPM1 mutated patients, 35% KMT2A. And you can see that this is now shifting a little bit more to what we expect in clinical practice. In fact, NPM1 is probably more five, six to one than KMT2A, but 80% NPM1 mutations, 20% KMT2A. And as Dr.
Issa and Stein both kind of alluded to the KMT2A subgroup going to be a younger patient population. You can see that in the median age here, 67 with KMT2A, 72 in NPM1 mutations. Overall median age was 71. I do want to point out that there is a 92-year-old patient, which is a patient of mine with NPM1 mutation, who is on this study. And I'll tell you that this patient actually recently enrolled, and his mission was actually to compete in a cornhole tournament. And when he was diagnosed with AML, when he was considering different options, that was his primary goal. And not only did he get there in this cycle, he actually crushed that cornhole tournament. So revumenib, I don't know, maybe it can provide some cornhole skills as well. 37% of patients over the age of 75.
You can see here overall bone marrow blast percentage, also an interesting note, slightly higher in the KMT2A subgroup compared with NPM1 mutations. This is our updated clinical outcomes of the study with the triplet of azacitidine, venetoclax, and Revuforj. 37 patients are evaluable for response. I showed you the 46 patients who've enrolled on the study to date. There are four patients who are not even at the level of marrow assessment at the end of their first cycle. There are several patients who had either come off study prior to the end of that first cycle or, unfortunately, had early mortality. This is looking at the 37 patients who are evaluable for response. 76% had an NPM1 mutation, 24% had a KMT2A rearrangement, 100% overall response rate. I think it's a really important point that Dr.
Stein really went through is that I think what's really most relevant here is overall response when you compare that to a CR/CRh or a composite CR rate, because these patients will ultimately recover their blood counts. It's just a matter of when, and with continuous therapy like this, we don't want to give patients too long of a time to recover their blood counts off therapy when that might lead to relapse and other complications, so there are two patients that achieved a marrow remission but did not recover their blood counts within a specified protocol time period, so we were just not able to call those patients responses. I think the really important points here that I also want to make, besides obviously this being an incredibly active regimen, is 84% of these patients achieved a marrow remission within the first cycle.
And when you look at the results of the VIALE-A study, that's closer to 40% of patients will achieve a remission. And that's all comers. This is obviously specific to the NPM1, KMT2A. These are really fast responses. And not only are these fast responses, 95% of these patients were flow MRD negative. And that is at any time period throughout the study, but these were almost all within the first one or two cycles of therapy. This was a centralized flow cytometric MRD assay. So really fast responses, really deep responses. And all these patients, when they get to the response assessment, are achieving a remission. And then the other, I think, important point here is, despite this being a continuous therapy and we're not waiting for full recovery, most of these patients are achieving a full remission with full recovery.
I think that speaks to this regimen being so active that their bone marrow is actually regenerating. These patients are not remaining in a myelosuppressed state throughout their therapy. We are seeing some CRh and CRi, but the majority of these responses are actually complete remissions. Some of these patients are now going to transplant. This is an older cohort. Not all of these patients, such as my 92-year-old, are going to proceed to an allogeneic stem cell transplant, but 27% of patients to date, and very few relapses on this study. We haven't seen any new safety signals. I'm going to go through some of the safety data that we have. This is very similar to what we've previously reported. We've had only one combined DLT at any of the dose levels, and this was a hematologic DLT.
And it was actually the first patient treated on the study whose platelets never recovered beyond the day 42 time period. And that was at the first dose level, and we did not see that in any subsequent patients. We did not see any grade 3 non-hematologic adverse events. Most common AEs are kind of what we've seen here. But looking specifically at differentiation syndrome and QTcF prolongation, which these are obviously really important adverse events of special interest, differentiation syndrome was probably quite similar to the overall rates that we see in single agent. And that's in contrast to Dr. Issa's data with this kind of combined triplet in the relapsed refractory setting. And I'm not sure if it's a numbers game or if there's really a difference in newly diagnosed versus relapsed refractory. But I think the similarity with Dr.
Issa's results is that we don't see a lot of grade 3 or higher DS on this study. In fact, none of these DSs were really severe or led to ICU stays or anything. QTcF prolongation is relatively common, up 43% of patients overall with the QTcF prolongation. But again, most of these patients are also on an azole, except our new cohort. And all these agents can also cause. In fact, azoles are one of the biggest culprits of QTcF prolongation. So unclear how much this is all revumenib specific, but grade 3 or higher is quite rare. And there was only one patient who actually required a dose reduction due to QTcF prolongation. Overall, we started looking at overall mortality. We don't have overall survival data right now, given that it's too premature.
A lot of our patients have actually enrolled in the most recent cohorts, although we're really hopeful to report this data soon. 28% of patients have, unfortunately, died on study to date. Very similar between both dose levels and across the NPM1 and KMT2A subgroups. I presented this data at EHA. This is a little bit confusing. I'm happy to walk through some of this if there's questions after. We wanted to look at the time of each of these cycles, how long of a delay was happening between each cycle. To kind of give you more kind of detail about why we kind of conducted this analysis, in order to proceed to any continuation cycle, the ANC had to be above 0.5 and the platelets had to be above 50.
In order to a complete remission threshold, your ANC needs to be above 1.0 or 1,000, and platelets need to be above 100 or 100,000. These were the parameters for each continuation cycle. After induction, which was either one or two cycles to achieve a remission, we looked at the median time to receive the subsequent first continuation cycle. This was a subset of patients. This is only the first 20 patients that we analyzed. The median duration of that induction phase was 36 days. That means that there was about an eight-day on average delay between the end of cycle, the end of their induction, and the beginning of their continuation phase cycle. Most of these patients actually required some delay. When we looked at dose level one versus two, you can see that there's no difference at all between dose levels.
Looking at all of this data, this looks very similar to the VIALE-A results with azacitidine alone without revumenib. This really suggests that this is a venetoclax issue more so than certainly a revumenib issue. We're now reducing venetoclax to 14 days with each continuation cycle. That's kind of mirroring Dr. Issa's study and lots of what we're doing in clinical practice to begin with. I think that will hopefully mitigate some of these cytopenias. We saw very similar kind of results with each of the continuation phase cycles. These patients are getting delays in between each cycle, but we think that that's predominantly venetoclax related. All that brings us to where we currently are in kind of the future development of this regimen.
We're obviously really excited about the incredibly high response rates, the ability to safely combine Revuforj with azacitidine and venetoclax in this kind of older adult patient population. We're in the planning stages of launching this randomized phase three study. This is going to be led by the HOVON group, and patients are going to be randomized between azacitidine, Revuforj versus azacitidine placebo. This is going to be predominantly in a newly diagnosed unfit NPM1 mutated population. So in order to be eligible, patients have to be over 75 or unfit for intensive chemotherapy. We are allowing KMT2A rearranged subgroups on this study, but the primary analysis will be in the NPM1 mutated cohort with a primary endpoint of overall survival.
And I think if our data continues to show this incredibly high response rate, I'm really hopeful that this could be potentially a new standard of care in the future for these patients. So I'll conclude by saying we have shown that we can safely combine revumenib with azacitidine and venetoclax. We haven't seen any new safety signals. We're still enrolling in our dose expansion cohort, randomizing between dose levels one and two to get really equal numbers and to best assess what is the optimal dose moving forward. This is a very highly active regimen. And we're seeing these remissions rapidly, deeply, which is really important. Our next steps on this study is we're going to finalize our first expansion cohort, which is up to 43 patients.
We're going to analyze that data, really present and publish that first kind of expansion up to that first expansion cohort, probably in the mid- to late 2025, hopefully present this data in an upcoming conference. And our goal is to initiate this randomized international global study of azacitidine, Revuforj versus azacitidine placebo, hopefully in the beginning part of 2025. And really excited about kind of moving this now to the front line, earlier line of therapy space for these patients. And hopefully, we can impact a broader group of patients beyond just the relapsed refractory setting. So thank you.
All right. Thank you to our presenters. What a great session. What great data. I really appreciate the anecdotal discussions on patients. Reminds us why we're here. These aren't just numbers. These are real people's lives. So just a couple of slides to close things up.
We'll move on to Q&A. I know people are eager to ask questions. 2024 was an incredibly productive year for Syndax. Two products approved, one on market, one soon to be on market. All the advancement of the data that we reviewed today in NPM1 dataset that's really ready to go for next year. So three things on the radar for Revuforj, as we can see here. Dr. Zeidner really just reviewed what is moving into the HOVON trial. This gets us into the front line. We will get there before anyone else does, particularly with this combination. We've seen the update on the NPM1 data. That data is moved to a publication. We will submit that by the later part of this year, and you'll see that publication in a peer-reviewed journal on NPM relapsed refractory mutant NPM1 data. That will appear in the very early parts of 2025.
Important for clinicians to see it, important for payers to see it, important for NCCN guidelines. And that then flows into an SNDA filing for relapsed refractory mutant NPM1 AML that we expect to submit in the first half of 2025. For Niktimvo, just as busy, as you know, we partner with Incyte on the development side as well as on the commercial side. We will launch this drug. It will launch in the very early parts of 2025 for chronic GVHD. We're excited. Patients are excited. Clinicians are certainly excited. Important that we find more value in Niktimvo. How do we enable the drug to treat more patients, move into bigger markets? That's represented by that second milestone for next year. And that is a frontline combination trial with steroids. There's another trial with Jakafi that's already ongoing.
And lastly, it's what Peter provided on that IPF trial, phase two. We would expect that to read out not in 2025, but in 2026. So an active year, a lot to look forward to, and a lot for us as an organization to deliver against. And we're confident that we will do that. So here's my last slide. We'll go right to Q&A and a little bit of a past, a present, and a future of Syndax. And if you think about where we were just a couple of years ago, anything before 2023, we were building out our clinical capabilities, regulatory, conducting trials. The company size was less than a third of what it is now, but we did a lot, really, the building blocks for what came next. And that takes us really to today. We'll call it 2023 and 2024.
Advanced our clinical expertise, regulatory, got two drugs approved through FDA. This is not easy stuff. Companies of all sizes, not every drug gets approved. So I think it says a lot. The accomplishments that we had, particularly over the last year, says what we can do, and here we are entering into a commercial stage as an organization, and we are fully ready to do that. We've built out our team, fully functional by the middle part of 2024, and on the cusp of doing some really amazing things. As we think about 2025 and beyond, we continue to transform as any company would at this stage, and it is really about delivering sustainable performance, profitable growth, and we are positioned to do that, and I would point to really three things that will enable us to do that. The first is the commercialization of first-in-class therapies.
We've given commercial views over time. Certainly, the data is great in those launch indications. We are ready to go, and there's no doubt we will deliver as a company to patients, to the treating community, and ultimately to the value of this organization. Second point I'd make is just about the financial foundation and structure of our company, and we are funded. We are funded straight through to profitability, and when you think about what we need to do, whether it's launch products and commercialize or develop them, we have enough funds to do both. And we're going to do both incredibly well, and the last is, what does the future bring beyond the current portfolio? I think it was seven or eight years ago, we didn't have either of the assets that we talked about today. They were licensed in.
And I think we've got capabilities and a track record to do that successfully and as needed to bring in products that are in spaces with a great deal of unmet need, with a lot of promise, develop them the right way, and take advantage of the commercial capabilities that we're building, and we'll prove how good we are in the coming year. So that's it for the presentation. I know we've got some time left, and we'll move to Q&A. And I will look to Sharon to find our first question.
Thank you. Anupam Rama from JPMorgan. Maybe for the acute leukemia KOLs, how have you incorporated Revuforj into your clinical practice here in the early innings? And how do you expect that to evolve? And have you used it in any NPM1 patients commercially? Then for you, Doc, on the axatilimab side, when you get your hands on Niktimvo with some of the organ-specific data that was presented on Saturday, how do you see incorporating that into your practice relative to, say, Rezurock? Thank you.
Yeah. I think the first question was on Revuforj and incorporating it into practice early days. I mean, the first, I was just sharing with Anjali, I think. I had a few patients that had started already on the commercial Revuforj. One is maintenance in Florida because they don't want to travel back and forth anymore to MD Anderson. And the Syndax team were great in getting them the drug. I have another patient who just couldn't get the transplant and couldn't get on study and got Revuforj. Also, the team helped. Regarding NPM1, I don't think we can start yet. There are still the studies.
So I haven't tried to do that, but I've had a lot of emails from physicians interested in the data and wanting to start Revuforj even in combinations. So this is outside clinical trial. They're just asking me questions on what doses they would use. Yeah.
Yeah, no, I agree. I think that I haven't had anyone I've started on Revuforj yet commercially. For NPM1, if you were at the satellite symposium that I moderated, I asked the panelists, "Would you give Revuforj for an NPM1 mutant relapse and refractory disease, assuming you could get insurance to pay for it?" And the answer was a yes across the board. And that's what I would do for sure. I mean, if you've got the choice between a drug that you know is active in this particular patient population and nothing, you pick the drug that's active. Yeah.
I agree with my colleagues. We have not used it commercially yet, but we're looking forward to getting started as soon as we have a potentially eligible patient. But I would have no problem trying to use this in an NPM1 mutated population, especially if that patient has exceeded all alternative therapies. So I think the data in NPM1 looks just as exciting as KMT2A. Whether insurance and so forth will cover it is a different question, probably.
Sure. I think the second question was on Niktimvo reacting to some of the data that was presented at the meeting.
So Peter is a CSO.
Yeah, no, no. I'm not a treating physician. So on the science side, all we had demonstrated is activity before or after or similar to Rezurock. So treating physicians can determine sort of the sequencing for themselves. But yeah, I can't answer that question.
Thanks. Brad here from Stifel. Maybe to Dr. Stein, in response to Dr. Issa's data, as you think about you and your colleagues, if you have a patient that's going to be a commercial patient, so not for one of your clinical trials, and you've got the availability of monotherapy, hopefully for both subgroups by the end of next year, do you see yourself reaching for monotherapy or trying to move towards some of these relapsed refractory combinations? And then to Dr. Zeidner, the BEAT AML data, anything you can say on what you're seeing in trends in OS for NPM1, particularly in the population that has the higher risk co-mutations where you pointed out OS was lagging for Vidaza? Thank you.
Yeah, maybe I'll start and kick it back to Dr. Stein. But we have not looked at OS, particularly between NPM1 versus KMT2A yet.
That's going to be certainly our next analysis point once we get that follow-up time that seems reliable. What I will say is that in our 26 initial patient cohort that we presented at EHA, we don't have all the mutation data in the 46 patients that I presented today. But in that first 26 patient cohort, 42% or so of patients on study had either an intermediate or lower benefit risk profile for Aza/Ven. So that includes FLT3-ITD, NRAS, KRAS, or TP53. There was actually one patient with a TP53 mutation. So that speaks to that this is not just a favorable risk group. Almost half of these patients had one of those other signaling mutations. And those are the patients that have really poor survival with Aza/Ven.
We're going to be very interested in those results, but I do not have the OS for those patients at this time.
Yeah. To answer your question about the relapsed refractory space, I mean, we would still reach for single agent unless we had a clinical trial like SAVE opened at our institution. We typically don't do combinations unless there's large, robust data sets and ideally randomized studies.
Yeah, thank you. Maybe one more for the KOLs. I guess for differentiation syndrome, is there a uniform diagnostic criteria across the different trials? We've been getting questions if it's fair to compare the DS from one trial to another.
That's a good question. I can take that one. So I don't think there's a uniform diagnostic criteria. There are diagnostic criteria, but certainly whether they're applied uniformly is completely unclear.
One thing, one data set I like pointing to about whether something is DS or not, if you look at the upfront AGILE study of IDH inhibitor with azacitidine versus placebo with azacitidine, in the placebo with azacitidine arm, the rate of differentiation syndrome, I think, was around 7% or 8%. Right? So that's your base rate of what people think is differentiation syndrome, but is not differentiation syndrome. So I think things can be called differentiation syndrome when they're not. I think things cannot be called different. It probably depends on practice patterns in various countries. I think that if there are menin studies that enroll primarily outside of the United States, those might have different rates of differentiation syndrome because of what doctors do in other locales. So I think that's an important point.
Next question.
Peter.
Thank you. Peter Lawson, Barclays. Just your thoughts on potentially delaying transplant in the front line if a patient's MRD negative, if that's kind of something that's kind of been percolating through the community. And then as we think about that relapsed refractory setting in the patients you were treating, what's the normal rate of transplant in those patients? And then kind of a follow-up question to that would just be, when you put patients on the maintenance setting, what kind of drives that?
So for the front line question, there is some data that guides us now from the U.K. on NPM1, and it's related to depth of remission. So if they achieve an MRD negative remission, that is a very good test, so 10 to the minus 5, so very sensitive assay, there is good data that we could probably not do transplant.
We don't have those measurements yet on menin inhibitor studies. This would be not flow cytometry. It would be NGS or PCR-based. But these tests are becoming more and more deployed in clinics. We're starting to use them. And I suspect these would guide this decision. There is a contribution of co-mutations that would make me do transplant regardless of MRD. For KMT2A, I would always go for transplant. For relapsed refractory, the rate of transplant really depends on the success of therapy. If there is no successful therapy, the chances of a transplant are less than, I don't know, 5%, I would say. I mean, they need to get to remission so they get to transplant. So seeing something that's 50% is considered relatively high.
The maintenance setting, what drives that for you before patients on or not post-transplant?
I would always try to do maintenance for the reasons I outlined. GVL takes time. If I decided to do transplant, they are probably high risk. If I have a therapy that has good efficacy and low toxicity, I would reach out for maintenance. We would still, I work at MD Anderson, so we do this a lot. Most often, this needs more data. But if I ask experts, if I ask my colleagues, they would probably reach out for maintenance for high-risk disease.
Great. Thank you.
David Dai from UBS. Two quick questions. One just on the follow-up on Brad's question on the relapsed refractory using combo, especially based on the safety that we've seen some impressive CR/CRh. So curious in terms of how much more data do we need to actually support usage of the combo versus monotherapy?
How soon do you think you can actually maybe get into the guideline for NCCN? That's the first question. Second, just around the QTc prolongation, we see some grade 4 QTc prolongation in the NPM1 study. How does that, is that concerning? How do you think that would affect your QTc monitoring and treatment paradigm?
The first question about what it takes to get on guidelines, I think just guidelines are made by experts that are looking at this data. I think they would just critically analyze the dataset and see if this is enough to advance what's available. I suspect there's a good chance it would make it to guidelines with this. This is not just one study on menin plus venetoclax. There are multiple studies on menin and venetoclax across various lines of therapy showing high synergy of venetoclax and menins.
So I think this is really promising. The grade 4 QT prolongation is something that is concerning. I wouldn't want it, but it's rare. And it wouldn't change how we monitor patients. The approach to do this is what Dr. Stein was saying, maximizing electrolytes and monitoring EKGs. But other medicines that we use often in leukemia have had the risk of cardiac arrhythmias. And it's all about the balance of risks and benefits. Leukemia is much more dangerous. So that wouldn't make me hesitate to treat a patient.
Phil.
Hi, Phil Nadeau from TD Cowen. One question for the company, then two for the physicians. First, for the company, on the updated NPM1 data, can you discuss why you did an updated analysis so soon after presenting the top line data?
And is this the final analysis that will be filed with the FDA and published, or will there be a subsequent analysis? That's the company's question. Two for the physicians. First, on BEAT AML, I apologize if I missed it. Could you give us some sense of the durability of the responses? And then second, broadly for the physicians, we saw data from a number of menin inhibitors on Saturday. Can you give us some sense how you distinguish between the different menins, assuming they're all ultimately going to be available? Thanks.
Maybe Neil, do you want to address the first question?
Yeah. So thanks for the question, Phil. So for the primary analysis was based on the N=64. So that was the analysis plan that was agreed prospectively with the agency with how the statistical design was done.
What happened was that there was increasing enthusiasm on the study, actually, as more and more data came out. So we had a lot of people wanting to participate in the study. We added sites to the study. And there were a lot of patients in screening by the time the data came to cut off the data. So we allowed the study to overrun to allow investigators the opportunity to participate and include additional patients. The reason that we reported out the N=64, as I mentioned, was that was the prospectively defined analysis. So we were obliged to report it. But we've decided now to report out the additional data because they are consistent, underlie the robustness of the original analysis, and I think they're of interest to the community.
Peter's next question was the next question.
Yeah. So durability is something obviously we're very interested in. And I don't have those numbers to share as far as the median duration of response. It's obviously a critical question, particularly with these results in front line. And that's definitely going to be included in our updated analysis. I mean, I can tell you anecdotally, we've certainly had patients beyond a year and some even beyond 12 cycles of front line triplet. Our enrollment has been really skewed over the last six to nine months. So almost 75% or so of patients have really had less than six months of follow-up. So it's probably not reliable to even speak on median duration of response, but we hope to have that updated data soon.
All right, Michael.
Thanks. Michael Schmidt with Guggenheim. Just a couple of follow-ups on BEAT AML. Obviously, super exciting response, right? Here early.
I guess, yeah, I mean, at the end of the day, what gives you confidence that this actually will result in prolonged overall survival? How do you think about potentially different outcomes in patients with co-mutations like FLT3 or IDH1/2? And then for the company, maybe just remind me and HOVON . What dose have you selected for revumenib and are using the full or the 14-day venetoclax regimen? Thanks so much.
I mean, I think for the confidence of OS, what gives me confidence is the incredibly high response rate and the MRD negativity of that response. So once you get to an MRD negative, in this case, this is flow-based 0.01% sensitivity, the goal is then to keep that durable, of course, with ongoing therapy. I shared some of the Aza/Ven historical control data.
In an overall NPM1 mutated population, CR rates are close to the overall population. So 66%, 67% median survival about 15 months. We're seeing a 100% response rate in that same subgroup. I would anticipate that would lead to an overall survival benefit. Of course, we won't know that answer until we have a randomized study. But that response rate gives me confidence. And I think not just seeing the response, but seeing the kinetics of the response.
There was a question on the dosing in the HOVON study.
Sorry, I missed the question. The question was again?
The dosing. How do we pick?
Yeah. So we're about to initiate the study at the 160 dose. So we've said that publicly before. I think we're in for missing the question.
Hi. Thanks. Yigal Nochomovitz from Citi. So a few questions on the front line study. So first off, you have OS as the primary. Did you consider MRD as a surrogate because that would be possibly faster to get to an answer?
So I'll couch this by saying that a lot of these, there's a lot of players in this study design. And I think that from an FDA standpoint, MRD is a really hard endpoint to achieve an approval. We don't even have a standardized MRD assay. So I think it would require probably a companion assay. And it leads to a lot more, I think, complexity. MRD negativity is going to be an obviously important endpoint, but to build it as a primary endpoint, I think would have been challenging in a study of this magnitude.
Okay. And then, of course, you shared the BEAT AML data. Now, that was for the unfit. So for the fit, what's the plan? I mean, we saw the data on Saturday from Zifto and Blexi and looked pretty much same from what I could tell, more or less. But what are you doing with Revuforj and plus seven three in the fit? What's the plan there?
I don't know if Neil wants to speak from a company standpoint. I mean, I could tell you with revumenib specifically, we are actually participating in an NCI-sponsored study of seven and three plus revumenib. It's a dose escalation study that's sponsored through the CTEP NCI. So we're enrolling on that study. And that's for KMT. That's younger fit patients with a KMT2A rearrangement or high-risk NPM1 features. There's lots of other intensive chemo combo studies that you heard yesterday or Saturday at ASH with Zifto and blexi menib. And obviously, it's a very competitive space.
But from revumenib specifically, that's the study that we're participating in. I don't know from a company standpoint for their development plans on the intensive chemo side. I can't speak to it.
In addition to that, there's a company-sponsored study with a slightly different variation of the seven plus three regimen, which is ongoing. And we've said that it's going well. So we're happy with the progress that we're making both with our own sponsored study and also the study that Josh just referred to. And so we're looking forward to communicating the data during 2025 and also updating our overall development plan with respect to the fit population.
And then the last one, it was interesting. Apparently, Syndax is the only company that's published the mutation resistance profiles. I'm curious why we haven't seen that from anyone else.
I think you can answer your own question. I mean, yeah. I mean, so the one thing I'll comment about the resistance data is that when you look at resistance data from other companies, it's not comparing apples to apples. So the resistance data that our group published with Scott Armstrong's group is a highly, highly sensitive digital droplet PCR assay that was tested really at every time point. So the resistance mutations may have been detected, but that didn't mean the patient relapsed. I mean, maybe they were ultimately going to relapse, but they didn't necessarily relapse. I think that it does say, I mean, either, I guess the charitable view is that the other companies don't have the ability to do this testing. And then there's an uncharitable view of why maybe they haven't been presenting that data.
Got it. Thank you.
That's great. So I think we're at time. I do want to thank our presenters for sharing and being here today. Your insight was terrific.