Good morning and welcome once again to TD Cowen's 6th Annual Oncology Innovation Summit, Insights for ASCO and EHA. I'm Phil Nadeau, one of Cowen's biotech analysts, and it's my pleasure to moderate a fireside chat with Syndax Pharmaceuticals. We have with us today CEO Michael Metzger and the Head of R&D, Nick Botwood. These are exciting times for Syndax with abstracts at EHA, as well as a launch going on, as I'm sure you're all aware, for Revuforj and AML. With that, Michael, I thought I'd kick it to you for an introduction. Can you give us a brief state of the company overview, biggest strengths, biggest challenges, and what do you think Syndax needs to achieve to drive up performance over the next year or two?
Yeah, first of all, thanks, Phil. Thanks for having us. Great to be with you. Exciting times for the company and really good to get into it and talk a little bit about it. Yeah, let me just kick it off with, you know, look, I think we're in an enviable position with two FDA-approved first-in-class medicines, best-in-class medicines that address really significant markets, multi-billion dollar markets. I think Revuforj, as you know, is a menin inhibitor, has what I would call significant first-mover advantage in this field. We are blazing the path here. It's a highly differentiated product profile, really compelling pivotal data across what I would say is the broadest population of patients covering AML, ALL, adults, and pediatrics. That's very significant. For Niktimvo, that drug is for cGVHD, offers a chronic GVHD, offers a really new mechanism.
is differentiated from other options that are available for cGVHD patients. It also offers a very significant opportunity. Both launches are in the early stages, but both launches are off to very good starts. We can talk a little bit about that. There is plenty of room for upside for sure. We are building every day. What is really important for us, we have a robust clinical development program and pipeline designed to unlock the future of these molecules and the multi-billion dollar potential for both. I think we are well positioned for success, both in the near term and the long term. It is evidenced by our submission of our sNDA for NPM1, which would be our second indication.
We hope to get that and expect to get that approved this year and expand the indication from there based on what, in some NPM1 talk, some of the data, how we expand into the front line. We did recently publish the NPM1 data. That's the subject of the submission in the journal Blood, so it's peer-reviewed. We think it stands up as best in class for that indication as well. We do expect to get into the guidelines for NPM1, potentially ahead of approval this year, which will be very important to the overall launch. Data is emerging both at EHA this coming meeting as well for future at the end of the year for the phase I data for 7+3 in the first line setting.
Lots of data coming that really fills out the profile and will help to substantiate our position in the market. Really to drive performance over the next 12 to 24 months, which I think is your question, Phil, really just need to deliver on these two product launches, which we continue to do and it is going quite well and really aggressively advance what we are doing to continue to develop both of these programs into the earlier line settings and expand the opportunities. Look, a $5 billion-plus market opportunity for Revuforj, $3 billion-plus market opportunity for Niktimvo in cGVHD. We have two products generating revenue, so we are in a very good place to expand from here. Good stuff.
That's a great overview. With that, we'll dive into each of those topics in a bit more detail. First on Revuforj, updated results from the AML trial were disclosed in EHA Abstracts. Can you provide some highlights of the data?
Sure, Nick, do you want to take that?
Yeah, thank you, Phil. Thank you for having us. Very happy to talk about our data. Yeah, going into EHA, we're going to have a strong presence at EHA firstly. I mean, we're actually going to be showcasing 10 abstracts, of which BEAT AML is one of them. There's going to be an oral presentation and we're proud of this collaboration with BEAT AML and we think the data are quite significant. You know, when I think about the data, as a medical oncologist, there are probably three things that I would draw your attention to as you think about it. Number one is that obviously this was a phase I-B study. Really in a phase I-B or phase I-B study, you want to confirm a dose to take into phase III. We were able to do that. We looked at two different doses.
We did not identify a maximum tolerated dose. We took our currently approved dose of 160 mg of Revuforj in combination with Venclexta into the phase III. The dose was well confirmed. The second thing you look for is tolerability. You know, can you combine these drugs safely with the standard of care, which is Venclexta? We were very well able to establish that there was good tolerability. Very few patients had to discontinue therapy for any toxicity. This is a tolerable and well tolerated regimen to take into combination. The third thing I think you look at in a relatively small single-arm study like this is evidence of activity.
When you look at a small single-arm phase II study like this, the end points I think you really want to focus on are complete response and then how deep and durable is that response rate. We saw really compelling evidence when you combine Revuforj with Venclexta with a 67% complete response rate. Now, what does that mean? The historical control for that from Venclexta's registration study is of the order of 37% CR. It is an order of magnitude different when you combine Revuforj with Venclexta. We are very encouraged by that. We know CR is an important endpoint in this setting and correlates very well with OS. We think that is encouraging.
The other endpoint you want to look at in terms of kind of, again, the depth and the durability of that response is the number of patients you can get into minimal residual disease negativity. This is a very important prognostic factor for how patients are going to do subsequently. We actually found in the 37 available patients for MRD, so almost the whole population, 43 patients were entered. In those available, all 37 were moved into MRD negativity. It was a 100% response on MRD negativity, even using a very sensitive flow cytometric approach. This is extremely encouraging. I would reference here the registration study for Venclexta alone, where the MRD negativity rate is just above 40%. It's a step change. In terms of survival, it's very early to be reporting on survival at this point. The median follow-up is about seven months.
I think in a single-arm study, you can't read too much into survival. We will be presenting a Kaplan-Meier of survival. You'll see at the Congress that it's immature. In the context of a single-arm study, I think really the focus should be on complete responses and MRD negativity.
Great. A couple of questions that we've been getting from investors on the abstract. The first is investors that have noted that CR rates declined somewhat from the data presented at ASH 2024. Any thoughts as to what's behind the decrease?
Yeah, you know, this actually just speaks to the population you look at. If you do an apples-to-apples comparison, there are two populations in these types of studies. One is the intent-to-treat population. This is essentially all the patients that were recruited into the study. And this is, I would suggest, the more rigorous measure. It's the measure we normally report on. We report on responses in all the patients that go into the study. The other population you can look at, which is a little different, is the evaluable population. So patients that were evaluable for response. If you actually look at the evaluable population, which has a slightly different denominator, and you look at overall response rate, actually the results from ASH 2024 and what we present at EHA are almost identically consistent.
The overall response rate is actually 100% in those patients that are evaluable for response. So really very consistent outcomes across the two populations.
Great. You referenced the CR data in particular as being much greater than what you'd expect from Venclexta. The skeptics note that the CR rate and median overall survival with AML, at least thus far, are similar to what Venclexta produced in the VALOR study. Is that fair? Which comparison is more valid?
I feel very confident in these data, predicting for a good outcome in the HOVON study, because CR is really the endpoint that is established as a meaningful endpoint and is shown to correlate with OS. It is CR that we've really shown a big magnitude of difference. Again, in a small sample size study, you have to focus on the endpoints that are most meaningful. I think if you focus on complete responses and MRD negativity, these are the best predictors for survival. As we update those data over time, I think you'll see changes in survival. It gives a degree of confidence that the HOVON study would read out positively for its endpoints.
Moving on to the pivotal data in NPM1, as Michael referenced, the results will be presented at EHA. How is the data that we're going to get at EHA different from the results presented at ASH last year and/or those published in Blood?
Yeah, we'll update the data and we'll continue to show, I think, a compelling profile. The safety will continue to be well tolerated. In terms of the efficacy, we'll have a slightly updated population. It'll be the first time we presented these data at a scientific symposium. When we enrolled the study, we defined the primary population to be 64 patients. Because of the enthusiasm to enroll into the study, we actually enrolled the population in the phase II portion of 77 patients. We'll be presenting all the patients, which I think is appropriate, that were enrolled into the phase II study. We'll actually be showing a CR CRh rate of 26%, which is, again, as Michael was saying, a best-in-class profile. I would also draw attention to response rate. Response rate is really important for physicians and patients.
If you look at response rate, this is one of the predictors that may actually help patients get on and subsequently get a stem cell transplant. We'll be reporting an overall response rate of just under half the patients. 48% in this updated data set will have a response. I think a quite compelling profile. We'll be presenting that as opposed to with some additional data points as well at the Congress.
Michael referenced the NCCN guidelines in his opening remarks. Can you give us a bit more of an update on those guidelines? Has the data from the Blood publication been submitted? Any sense when Revuforj could be incorporated into the?
Yeah, absolutely. Firstly, we were delighted to have the data published in Blood in a leading peer-reviewed journal. We submitted that to the guidelines, of course, on the day of publication. The timing was actually very good because we know the NCCN have a committee meeting on, I think, May 19. It was timely for them to receive that submission from us for consideration. We're optimistic given the profile of the data that this will lead to a favorable outcome. I'm hopeful we'd see an update to the guidelines most likely in this quarter. We'll let that process play out. I think we remain optimistic given what we presented.
Maybe one last question on Revuforj at EHA. At EHA, there will be a post-presentation reporting outcome in patients with the NUP98::NSD1 mutation. What's the significance of this data?
Yeah, this is interesting. This, I think, speaks to the science and our leading in the science. NUP98 is an interesting mutation type. It's a relatively rare mutation type, but patients have a poor prognosis. We'll be presenting a small series from our data set. This is actually N of five patients. Interestingly, in these five patients who otherwise have very little treatment options, 60%, so three out of the five, actually had a morphological remission. That's quite significant. Indeed, one of those patients then subsequently went on to get a transplant. As is becoming common practice, went back on to Revuforj after transplant. As of data cutoff, have had 10 cycles of therapy, which is quite encouraging. I think this speaks to the potential breadth of Revuforj in terms of its applicability in acute leukemias.
We have a collaboration with Dr. Issa at MD Anderson, actually looking at all of the subsets of AML that are thought to be driven through Hox upregulation, which of course includes the NUP98::NSD1 genetic alteration and indeed other genetic alterations that could be driven through that Hox upregulation. I think the reason that this is important and relevant is that this could have applicability for up to 50% of the population with acute myeloid leukemia. Obviously at the moment, our focus is on our approved indication KMT2A, NPM1. What I think is important is there are other genetic alterations that share the same pathway that could have broad applicability for Revuforj.
We expect a number of updates from other menin inhibitors at both ASCO and EHA. Some of those updates will feature Kura's ziftomenib, Sumitomo's enzomenib, and J&J's bleximenib. What's your impression of the data from these agents that will be presented at the meeting and how the competitive environment is evolving for Revuforj?
You know, first, I mean, we're the only approved menin inhibitor currently. We know that the physicians like the profile. They like what they see. They're getting familiarity with using it. That's an important point to make. The second point I would make is we probably have the, or we have the broadest approvals because if you think about our data that spans our current approval for KMT2A in AML and ALL. This, of course, also includes the pediatric population. Obviously, we're anticipating our sNDA for the NPM1 population later this year. You know, when I look across all of the other agents that inhibit menin, I don't see anything that's at all differentiating. Physicians are very familiar with our profile. There's nothing really that we see that would warrant any change because we have a best-in-class profile.
I think it's important when you look at the efficacy parameters that matter to physicians and patients, whether you look at the response rate, whether you look at the duration of response, whether you look at the MRD negativity, or whether you look at the proportion of patients that actually subsequently can then go on to get a transplant, across all of those parameters, Revuforj posts numerically the highest numbers. I think we remain really quite confident in the profile in terms of being best in class. The physicians are very much liking what they see.
Great. One last quick clinical question before turning to the launches. You've initiated the Evolve 2 frontline trial with Venclexta. What are your plans for the initiation of other trials beyond Evolve 2 in the first line and maintenance settings? When could those trials be up and running?
Yeah, and thank you, Phil. We're excited about the transition and the evolution of Revuforj into the frontline setting and in combination with current standards of care. Obviously, HOVON is leading the way there. We have first patient, first visit. It is enrolling. We think that's a really important unmet need. We're excited about the synergies we've seen with Venclexta. That study is going. That will address what we called kind of the unfit or elderly population. In terms of the fit population, the way we're thinking about this is KMT2A patients or younger, fitter patients that will receive intensive chemotherapy, the so-called 7+3 regimen. We're thinking about this for both KMT2A and NPM1 patients. We have two phase I studies actually ongoing, establishing a tolerable dose that we plan to take into phase III.
We will run two randomized control studies that we're actively looking to set up and would hope to have enrolling towards the back end of this year. We will provide more details on the design of those studies later in the year. It remains a high priority for me and the team. We are kind of moving swiftly to get those studies up and running and more on that to come.
One of your potential competitors is using CR and MRD negative CR as potential registration endpoints for accelerated approval. Is that possible in your clinical trial program as well?
Yes, very much so. Of course, we've already built in complete response rate in with the HOVON trial. That's important. That's a dual primary endpoint, which essentially means that CR and OS are independently powered. We think that complete response rate could serve an accelerated approval in that unfit population. Similarly, as we're thinking about the fit population, we are considering in particular MRD negativity. This is a different population, but we think MRD negativity, particularly when you measure it in bone marrow, could serve as an important surrogate predicting for event-free survival and survival subsequently. That's something we're actively looking to build into the studies to serve as a potential for accelerated approval. We will provide more details on that towards the latter part of this year when we get those studies posted.
That's great. Turning to the launches, I guess first on Revuforj, what's the most recent update on the launch? Can you in particular disclose the launch metrics that you talked about on the earnings call and what metrics will you be providing during future calls?
Yeah, thanks, Phil. Look, I think, as I said earlier, we're off to a very strong start with Revuforj. First full quarter, $20 million in revenue, which is the largest, I think, quarter we've ever seen for a drug in AML, first quarter. That's comparing to other drugs doing quite well and surpassing even our own expectations in some ways. I think it really performance bolsters our confidence in the number of patients that are out there with KMT2A translocations and certainly highlights the significant opportunity we have with the drug. I think we highlighted on the call both the expanding breadth and depth of prescribing. So 44% of our high priority or what we call tier one or two accounts ordering by the end of as of the end of March. That number has continued to grow throughout the second quarter for sure.
We have made really great progress with the priority accounts. More room for growth, additional depth and breadth building. We will continue to track that. Those are important metrics. Beyond the tier one and tier two and mostly academic centers, we are moving more thoroughly into community practices. We do have a very sizable commercial-facing team where we can cover all 2,000 accounts, tier one through tier four. We are making progress moving into the community as well. In terms of formal coverage or coverage policies, they are in place for as of the end of the quarter, we said 72% of the managed care lives, including commercial Medicare and Medicaid. That has continued to build and is nearing completion. We feel quite good about getting coverage so early and so universally.
As Nick pointed out, the feedback from clinicians on the product profile, ease of use, ease of access, all really, really strong. Overall, it's about patients, penetration, and persistence, right? We can talk about persistence too. I think those are the things that we will track and continue to give people some understanding on as we roll through the launch. Really, for these clinicians and patients, it's about a best-in-class experience. To us, that will help us drive the long-term competitive immunity that we hope to have over many years as we build this franchise.
In that initial $20 million sales figure, what portion of that revenue came from KMT2A patients versus NPM1 patients? How do you expect that to evolve once NPM1 reimbursement is secured?
Yeah, I think, there really hasn't been any barrier to getting the drug paid for, whether it's on label or not. I think what we seem to feel and believe about the launch is it's about probably 90% KMT2A on label, probably 10% is being written off label. We do expect that with the inclusion in guidelines for NPM1, that number of NPM1 patients will continue to build. Of course, when we get the drug approved and have the full support of the commercial team on promotion, that drug, the NPM1 portion will build as well. I think there's a lot more to do in KMT2A. We expect by the end of the year, we could be as much as 50% penetrated new patients by that point, which would be fantastic and a great result in a year one. NPM1 will follow.
There's a lot more to do, but we feel that the NPM1 will certainly provide another leg up as we go throughout the year here and build towards approval.
Diving into that point in a bit more detail, what do you think is the most important catalyst to getting NPM1 patients on therapy? Do you think it's the inclusion in the NCCN treatment guidelines, or is it the approval, or are both of those kind of equal where you'd expect a step up in NPM1 patients with both?
Yeah, I do expect a step up with both. I do think that getting on guidelines, having the first drug approved and also ultimately approved, but being in guidelines ahead of approval, physicians practice to guidelines, right? We know that. It does provide some formulary aid as well. I think there's great opportunity here as the only menin inhibitor approved to have a second indication in guidelines ahead of its formal approval. I think that could provide quite an ample opportunity. Of course, yes, I do believe that we'll be adding significantly once we get the drug fully approved.
Great. Last couple of minutes, we'll turn to Niktimvo . First, there are four posters at EHA. Niktimvo , most seem to be on-call presentations. Are there any notable new data presentations from the posters that you'd like to highlight?
Yeah, Phil, we're excited to have those four posters there. A couple of things I would draw attention to. One is that one dataset will demonstrate that actually you see very good activity with Niktimvo across lines of therapy. In our AGAVE-201 study, we treated patients across different lines of therapy. Actually, when you treat patients a little earlier in therapy, if anything, the response rate is a little favorable. I think this speaks to the potential for Niktimvo to be used in earlier lines of therapy. That's obviously something we're exploring now in randomized control studies. I think that's important. That's the first thing. The second is that we saw very rapid improvement in symptoms. This is across organ classes because you have to remember that chronic graft-versus-host disease is a multi-systems disorder.
We saw improvement in symptoms across all the different organ systems quite rapidly, many within six cycles of starting therapy. That is about 84 days. It speaks to the activity of CSF-1R in this disease that you get rapid onset of symptom alleviation across the symptoms. Those are probably the two take homes from the data we will be presenting.
Niktimvo also had an impressive sales number in Q1. Could you review the sales metrics and your expectations for the uptake of Niktimvo?
Yes, certainly. I think it's off to a very strong start. Incyte, our partner, they recorded $13.6 million in Niktimvo net revenue for the first two months of the launch. This started in February. That's a pretty significant start to any launch. This market opportunity, we think, has a lot of potential for us to tap into. I think some of the things that we talked about, 95% of top accounts have ordered. I think that has only increased. We're talking about 200 accounts in the U.S., roughly. 70% of all the bone marrow transplant centers had ordered by the time of the call. I think all of those metrics have really increased. Formulary coverage is high. We're continuing to build that. Product's being reimbursed. It's being delivered to patients.
The physicians are reporting that they really like the product. They like the profile. It offers something unique in the mechanism of action, both dealing with inflammation and fibrosis. That has been really well received. Look, I think the trajectory here is only up. We talked about the EAP patients coming over and starting to build. Only 50% had been moved over to commercial drug as at the time of the quarter. We expect that the second half of that 50% will go on paid drug by the second quarter or throughout the second quarter. We do expect this to be a very significant launch with an analog out there for Rezurock, annualizing it over $500 million in its third year. We think we can do as well or better.
This is a very significant opportunity in chronic GVHD, which we think we bring something very unique to.
Great. With that, we'll take a run of time. Thanks so much for a great overview. We look forward to seeing you in Chicago this weekend.
Fantastic. Thank you, Phil. Good to see you.