Okay, great. Well, thanks everyone to come to the UBS Healthcare Conference. It's our pleasure to welcome Syndax Pharmaceuticals. My name is David Dai. I'm one of the biotech analysts here at the UBS platform. So we have Anjali Ganguli, Chief Business Officer and Chief Strategy Officer, you know, with us today. So, Anjali, welcome.
Thank you, David. It's a pleasure to be here.
Great. And so, you know, Syndax is a very interesting story, one of the leaders in the menin inhibitor space. And so for the audience here who are new to the story, maybe you can just give a quick overview of Syndax Pharmaceuticals.
Yeah, happy to. So, thank you again for the invite. And, for those who aren't following our story, Syndax is a commercial stage company. We transitioned to commercial stage, this past August with the approval of our first molecule, Niktimvo, for chronic graft-versus-host disease. And exciting enough, we have another asset under review with the FDA, and our PDUFA date is December 26th, so soon to be two approvals, our hope. Both of these assets are first-in-class, best-in-class molecules targeting multi-billion-dollar opportunities at their initial indication. And we see significant development opportunities beyond that. And we've started trials in areas to move both products upline as well as into other tumor types or indications, more broadly. We've built a commercial field force. Our team is in place. They're ready to launch our products. And we've also had a lot of news recently.
We did a royalty financing with Niktimvo and brought in $350 million. We announced that last week. So we believe we are funded through profitability now and could do all the work on development and commercialization to launch these products. We also just Tuesday had some really exciting news on another indication with revumenib, our menin inhibitor. That's the one under review today for NPM1 AML. So we believe we have a second approvable data set that we can file with the NDA or with the FDA through a supplementary NDA in the first half of next year. So it could have a second potential launch in 2025. Yeah, we're just excited with where we are and what's in our future.
Excellent. Yeah, great. Many interesting near-term catalyst milestones to watch. Of course, the near-term one that everybody's looking at is gonna be the revumenib approval, the FDA approval in December 26th, as you mentioned. I think the Street already expected pretty much an approval for this one, but there are some questions around just labels. Can you just help understand what the label is gonna look like, what's the expectation for the label here, Anjali?
Yeah. I mean, I think the label is going to be very consistent with the population we treated, the indication, you know, the relapsed/ refractory population. And so I don't think people should expect any surprises, but I think it'll be very on par with other labels in this space.
Got it. And then what about the things like, you know, black box warning, QTc prolongation, any thoughts around, you know, you know, around that as well?
Yeah. I mean, I don't wanna go into too much detail. We you know are currently in active discussions with the FDA. And as I said, our approval is coming very shortly. But you know what we've guided to is we expect to see a black box for differentiation syndrome. It is an on-target effect that's really been seen with all of these targeted agents in AML. And it's more of a warning for physicians to be aware and cognizant of this issue when they're managing their patients. But it hasn't been something that's really impacted the development of revumenib, maybe in contrast to some of the other menin inhibitors. And we've also guided that we don't expect a black box for QT prolongation.
Got it. So very much consistent. And, you know, there shouldn't be any surprises for the label overall.
That's right.
Got it. Great. And of course, the launch, everybody's looking at that as well. So ahead of launch, you know, can you just tell us about the commercial team and commercial preparations that you're doing right now?
Yeah. No, that's been really exciting watching the company transition into a commercial stage company. So we were preparing for a 3Q launch in case the review came very early. And so we hired the field force. We brought in a, a number of very experienced reps. They have on average 20 years under their belt, in this space, six prior launches. They've got significant networks already built up. And so because they're, on the ground, we, they're out there talking to physicians, profiling the accounts, making sure we understand diagnostics, process, the pathology, the systems of care, you know, what, what physicians need in order to seamlessly prescribe and address their patients. And so, you know, it's given us even more time to be ready to go. And I think, it's, it's been, really exciting.
I think the other really important point to emphasize is we're very focused on the patient experience and making sure patients also have a very good, you know, support for use and physicians understand, you know, that we're here to help them through this journey. So yeah, it's been in place and they're just waiting for the green light from FDA.
Yeah. That, that's excellent. So maybe just, you know, help us understand some of the initial expectation, on the launch. Maybe, you know, what have you heard so far from physicians, on the overall receptivity for revumenib in KMT2A AML? And what do you think that ramp is gonna look like over the first few quarters?
Yeah. I will tell you, I've been in this industry and worked in sort of the forecasting space since I joined, you know, since I joined. It's probably been 15-20 years. And I have not seen such support from the physician community as we have seen with revumenib. It is extremely exciting to be part of this process. And, you know, this is a very young patient population. Unlike most AML, you know, the median age in our trial was 34 years. There's a lot of motivation to try to help these patients live longer lives. And they really have nothing today.
So, giving them a drug that, you know, in the trial experience where it was later line patients, we were getting 2/3 to tumor clearance and giving them the ability to do what they would like to do with these patients, which is take them to transplant and keep them, you know, lower the risk of relapse as much as possible, which includes putting them back on revumenib after transplant because of the, you know, tolerability profile and the efficacy of the drug. So, they've been very, very excited and looking forward, very much looking forward to having this available for their patients. That being said, I think it makes it hard to identify a true analog for uptake, you know, there's a couple things that have changed versus the other targeted therapies that have launched in this space.
So, you know, when the IDH inhibitors and FLT3 inhibitors first launched, that was the beginning of targeted therapy. So identifying the genotype of patients was new. And I think over that time, it's become very standard. You know, even the ability to diagnose and identify patients has become easier and faster. So that dynamic, I think, is working in our favor. These patients are identified already, and reimbursed for those diagnostic tests. So there's a lot of hurdles that don't exist on that front. I think the other point that we were talking about earlier, where we'll have an approval in KMT2A, we've just put out data in another indication that also has no available therapies for these patients. And it represents the first pivotal data set in relapsed/ refractory NPM1 patients.
Again, with an oral agent that's well tolerated and very efficacious, physicians are telling us this could be our second line option for these patients. We know exactly what to expect. We can manage patients as we need to with revumenib and feel very, very confident about getting them to respond. So that adds to the potential launch curve. We've also been generating some really outstanding data in combination with venetoclax-based regimens as well as chemo-based regimens in the relapsed/ refractory setting and in the front line. I think all of that data is, we're gonna have some updates at ASH next month. But all of that evidence is really compelling to physicians. I think it changes the trajectory. It's not launching just for one indication, one patient population. So I think we're really excited.
We think it's gonna be a really strong launch, and as I said, we have built a really strong team to make it happen.
Yeah. No, that's just great. What about the duration of treatment for revumenib in KMT2A? You know, what is the number look like for the duration of treatment?
Yeah. Right now, our estimate is about nine months on average, across the different populations. The way we think about it is, the patients we treated in the pivotal trial kind of fell into two categories. I mean, obviously responders and non-responders. The responders, as I said, was about 2/3 of the patient. 'Cause for physicians, what's important is clearing the tumor burden. And that was, that includes, measures beyond CR/CRh. So getting a CRi, CRp, or even MLFS is important because all of those metrics indicate a clearance of, of tumor blasts. And they all enable patients to go to transplant, especially because those responses are MRD negative responses, which is the best correlate to success post-transplant. So 2/3 of the patients responded. And what we saw in the KMT2A population, again, because they were so much younger, we saw almost half of those patients go to transplant.
And then physicians were putting patients on revumenib post-transplant in order to maintain that remission and, you know, decrease the risk of relapse. So that could really extend the duration of treatment significantly. And right now we're estimating, you know, the pre and post-transplant treatment could be around a median of 18 months. We don't really know. We've seen patients stay on three years post-transplant. We've seen, you know, there will be some patients that, you know, unfortunately don't make it through transplant long enough to get back on therapy. So there is a range. And today we estimate a median of 18 months. There's also the other third of patients that responded but didn't go to transplant. It looks like the median duration in this third -line population we treated was about eight months. And then we have the non-responders that are about three months.
And so that averages out to about nine months overall. I will say, you know, as we talk to physicians and going back to the question about their excitement and interest in the drug, they see this as a second- line therapy. There's really nothing that exists today. And so as soon as they can use it, they want to. And I think as we've seen in oncology more generally, the earlier you treat, the better patients do, the longer they respond. And so I think all of those numbers have upside as we move to second-l ine. Maybe more patients can go to transplant as well as being able to keep them on therapy longer. So that, that's where we are today. We'll see, you know, we'll be monitoring in the real world, how things go.
Got it. That's really helpful commentary here, and maybe just for the audience here, just tell us anything about the KMT2A market. How big do you think, do you estimate the market is?
Yeah. We think the total addressable market for KMT2A is somewhere around $750 million, in the U.S. alone. And that's based on, you know, sort of the duration of therapy, which we just talked about, the epidemiology of this patients. And remember, it's not just AML, but it also includes ALL. And it's thought to be about 10% of both those populations. And then our price point, which we've guided to somewhere between $35,000-$40,000. And that's substantiated by current therapies that are launched and on the market. And so, you know, doing the math, you get to about $750 million in that population. And what's great for Syndax is there's really no competition in this population.
You know, we've seen with other targeted agents in oncology. It isn't a surprise to see these agents owning, you know, 85%-90% of their market. We think we have a really great place to start. As we talked about NPM1, we'll further expand the potential value in relapsed/ refractory. We are looking to go into front line and make sure revumenib becomes almost the backbone for these patients with KMT2A and NPM1 mutations.
Yeah. That's actually a good segue to start talking about the NPM1 data that you just reported a couple of days ago. So maybe, for the audience here, just to highlight some of the key updates that we saw from that data update.
Yeah. No, I mean, we were very excited about the data. I think it was exactly what we were thinking and hoping for. It's very consistent with what we've seen in KMT2A. And that's how we've been talking about the mechanism and the expectation. It's also similar to what other menin inhibitors, you know, with the exception of one, have suggested they're seeing. You know, J&J and Sumitomo have been very deliberate about saying their efficacy and safety across their populations with each of their drugs looks consistent, and it makes sense biologically. You're hitting the same target. You're inhibiting the same interaction to drive the same effect, and so, you know, we think we've produced another approvable data set. And as I said, we'll look to submit an sNDA in the first half of 2025.
But just to reprise the data, you know, we saw an overall response rate of 50%. 64% of those patients were MRD negative, so deep, durable response, deep, deep responses. We saw a duration of therapy of, oh, sorry, we saw a CR/CRh rate of 23.4% and a duration of that CR/CRh of 4.7 months, and the safety and tolerability again look very consistent with KMT2A. We had less than 5% discontinuations, I think, which emphasizes the ability of patients to stay on drug and manage through their disease. I will emphasize that the population we're treating here with NPM1 is a much older patient population. It was 34 on average in KMT2A. Here it was 65, so with that age, you see additional comorbidities, a little bit more sensitivity to treatments.
I think those are reflected a little bit in minor, you know, minor shifts in the safety, but overall, we think this drug has performed very, very consistently. We know predictably across both patient populations.
Got it. Yeah. I think the CR/CRh and duration of response was in line with our expectation as well. But I think the Street was potentially looking at a little bit higher. You know, the expectation was around close to about 30% because of the competitor from Kura, ziftomenib. And so maybe just help level set, you know, the 23% CR/CRh and the ORR, and duration of response in terms of what it means for the patients here.
Yeah. Sure. So, you know, and also, revumenib had put out a 36% CR/CRh rate in phase I as well. So, you know, there was some expectation in that range. However, we feel like the data we presented today is actually fairly consistent with those point estimates based on very small patient numbers. So the confidence interval on that 23% includes a range of 14%-36%. So includes the point estimates from the phase I for both molecules. I think it's just as you bring more patients into the fold, you get more confidence around the mean. And that's what we see. You know, it's a matter of a couple of patients to get to 30%. And is that a meaningful difference? You know, I think that's questionable.
What, and again, I would say we've tested over 300 patients in our entire monotherapy experience. And, you know, all data is kind of pointing to a very similar point estimate and confidence interval. Obviously, some patients do better than others. The overall response rate, again, I will go back to that, is always been in the 50%-60% range. And that is what physicians focus on. Really, the number one thing you want an anti-leukemic agent to do is get rid of the leukemia. And that is actually measured by the overall response rate. And then the question is, can they get to a full recovery of their blood composition? And that may be because of how a drug interacts with the patient. But it's also very much based on what prior experiences the patient had, and how their disease, how extensive their disease was.
Because leukemia is a disease of the blood, it impacts the platelets and neutrophils to begin with. So that can impact where you're starting from in terms of composition. But then if you have prior therapies like chemo, like venetoclax, even prior stem cell transplant, that can really impact and injure your bone marrow, which makes it harder for patients to fully recover to a CR or CRh. And in the population we treated, there was, you know, two prior lines of therapy, but 75% of those patients were treated with venetoclax. I think that's been a phenomenon that's continued to grow. You know, venetoclax has been an effective agent in AML. And it was initially approved at the, and an accelerated approval in the end of 2019.
Through the course of us developing menin inhibitors, physicians have also gotten more comfortable using venetoclax in their population. So we've, I think that's also been an impact on how the phase I data compares to the phase II and the ability to recover, the patients to recover to normal blood composition could be impacted there. But I think, you know, for physicians that we've talked to, they have wholeheartedly been so excited about this agent. And, you know, it's, it's not just one point estimate that means the drug is effective and, and, exciting for them to use. It's the totality, the evidence. So the safety is very manageable. You know, we had a thought leader, Dr. Eytan Stein, on our call. And he's, you know, he's been very involved in the development of many targeted agents in AML.
He couldn't emphasize enough that this tolerability profile is very easy for him to manage. He's had minimum to no discontinuations because of any side effect he's seen with revumenib. He thinks, you know, he's actually said on a call that he tells us, tells his patients, the side effect is you're gonna feel better. You know, so it's really quite incredible to have that kind of support and to give physicians something that they're excited to use and they feel like will really help their population.
Got it. Yeah. No, that's really helpful commentary. Just regarding that 75% prior venetoclax population in your trial, how should we think about this in the real world? Would you say that's relatively consistent where a lot of patients are being treated with that prior event, or could that population be lower?
No, I think it's sort of what I was alluding to in the last comment. Like, venetoclax was approved first for CLL, and then it's moved into AML at the end of 2019. That was an accelerated approval. The confirmatory trial read out, I think, early 2021. I think that data that they generated was very strong in AML, and it treats a broad population and it's front line in the unfit, you know, it was significant improvement over azacitidine alone in the unfit population. Physicians have learned to manage some of the issues with venetoclax, namely the cytopenias by changing the dosing frequency from 28-day cycles down to 21, 14, and in some cases even seven days to get to a very similar efficacy and mitigate some of the safety issues.
I think with all of that evidence and experience, venetoclax has become more and more of a standard of care, even to the fact that there's some interesting trials going on to see if you could displace chemotherapy with venetoclax-based regimens in the fit population and still get to, you know, similar efficacy. I think there's been a slight lag in uptake of venetoclax in Europe because it was approved a little bit later. And so I think the phase I populations that were tested, for instance, may have had less venetoclax, because of both the timing, but also where they enrolled patients. But over time, I think it's going to be a standard of care, which is why we're doing our pivotal trial on top of venetoclax.
You know, we feel like that is what physicians wanna do, and it is the best thing for their patients.
Got it. Yeah. You alluded to the some of the safety, you know, things we saw. And I actually received an email question just regarding that safety. And the question asks, when the FDA makes decision on the KMT2A label for revumenib, for the PDUFA, will they take into consideration the NPM1 safety data, such as the grade 4 QTc prolongation or differentiation syndrome?
Yeah. I mean, it will be a very separate filing for the totality of the NPM1 data. But during, we were obviously enrolling patients in the NPM1 cohort at the same time as the KMT2A. And the FDA will look at all the safety information that you have to date. So we've provided them information on the totality of the patient experience that we had as of the data cut, which included patients with NPM1. And so they've seen, I don't know what percentage, but they've seen a portion of the data with NPM1. And then they'll see more in the sNDA filing when we submit for NPM1. But again, I think there's, you know, we're under a Real-Time Oncology Review with them, and there's a lot of dialogue back and forth. So I think they're very aware of everything that's happening with the program, monotherapy combination.
They're working with us to get this drug as quickly as possible, and the pediatric population, they were urging us to expand to younger patients, in the beginning, so I think they know a lot about our drug, and they'll obviously learn more soon once they submit the sNDA, but I also think that this experience with them and sharing all this information will also help and accrue to the benefit of the sNDA filing because we're just adding slightly more information to what they've already seen and just interrogated, so I think the answer generally is yes.
Got it. No, that's really helpful comments. So on that, sNDA filing they plan to do in first half 2025, how soon do we think we could actually potentially get an approval? How fast would the review timeline look like?
Yeah. It's hard to know. I mean, obviously we weren't perfect in guessing how fast our current NDA would get approved. But I think in general, sNDAs are shorter than NDAs. And so the estimate we've had in our head is about six months. But you know, depending on do we get priority review, do we do BTD, all these things, it could shift how much time FDA spends on the you know to review it quickly.
Got it. And then based on your experience with the KMT2A, you know, filing, I would imagine you've already, you know, have that experience to, like, you know, expedite that filing process, right? And, you know, getting together all the package. So six months, you know, that, I think that will make sense. So second half 2025, that's when we should be.
It's possible.
Expecting.
Yeah. I think we'll give more guidance when we have a better sense of when the package goes in. But yeah, it's not, definitely not, out of the options.
Great. Now we have about six minutes left. I do wanna touch base on your second program.
Sure.
Niktimvo, which is, you know, quite interesting. And recently you closed a deal with Royalty Pharma, $350 million, you know, for 13.8% of the royalty from Niktimvo. So, you know, just help us understand the structure and the process that, you know, went through to, you know, to actually ultimately get that deal there.
Yeah. No, it is. It's an extremely exciting deal for us. I think we have been, and I'm sure you know, a little bit frustrated with the lack of value that the Street has put towards axatilimab. And we think it's an extremely valuable agent. It's a best-in-class therapy. It works very well in chronic graft-versus-host disease. And we have evidence to believe it should work broadly in other indications. And it's even taking us a little bit outside of oncology to IPF and potentially other places. So we are so excited about what that drug can do and what value it could generate. And, you know, Royalty Pharma came to us with a very similar mindset. They proposed a deal because they see value in axatilimab that was not being ascribed. And it made a lot of sense to us.
So, so you're right. We, it's a 13.8% royalty on overall revenues. We share axatilimab or Niktimvo with Incyte in a 50/50 profit split. And despite that 13.8% royalty, we still see substantial, we believe we'll see substantial revenue or significant revenue from axatilimab over time. I think importantly, the deal is capped at 2.35 x the initial investment. So it gives us an opportunity to still participate significantly in any upside for some of these other indications, as well as moving into front line and growing the value in GvHD. I think the other really critical point is that the GvHD market has been very undervalued across the board. You know, I think Sanofi was a player that stepped up and realized that there's a lot of value here. And I think they're absolutely right. They're seeing really strong uptake for REZUROCK.
You know, I think annualizing over $500 million in the third full year of sales, which is really impressive. We don't see why axatilimab or Niktimvo would be any different. You know, it's a very distinct mechanism. It has the potential to address both the inflammatory issues, but also fibrotic issues, which is really what drives the unfortunate incidents of death and this end organ damage and death for these patients. You know, bringing this in as a tool for physicians could really change how GvHD is treated and even the progression of disease. So I think they're very eager to see how axatilimab could work in earlier lines and what it could do for patients overall in GvHD.
And then, you know, the antifibrotic axis, as I said, is also plays an important part in many other diseases. So yeah, we're really excited that $350 million combined with the current cash we had on hand gives us a balance sheet of about $750 million. And we think, gives us funding through profitability. So we may never have to go out to the Street again, which I think is a really strong position for us, and allows us to do what we need to do from a development perspective, for these assets and maybe even bring in some other assets to continue to build the company.
Got it. And so just ahead of the launch, any kind of thoughts around the commercial preparation and between you and partner Incyte, who's gonna be driving most of the commercial, you know, commercial team for Niktimvo?
Yeah. So the deal we signed with Incyte, we have the potential to provide, and we opted in to provide 30% of the commercial effort. So they will have the majority of that effort. They are the leader in the GvHD space and really have built the branded opportunity here, which is one of the main, major drivers for us to do this deal. I think it gives, you know, reduces a lot of hurdles on patient support and access to physicians and, you know, potentially speeds up the ramp to adoption. But you know, it's not a huge field force necessary to address the physicians that will be making decisions on a GvHD, a GvHD drug. I mean, I think Sanofi launched with somewhere around 18 reps to manage, and they've done a very good job with those reps.
So, you know, we feel like the footprint we've built for revumenib totally encompasses what we need for axatilimab. And it gives our physicians, our reps something also, another very interesting agent to talk about. And I think makes it easier for them to go talk to those physicians because now they have two really compelling assets to bring them. And so it helps. I think it helps the revumenib launch and it helps us on a cost basis because, you know, the percentage of reps that will be detailing axatilimab will be shared with the Incyte P&L. So yeah. And it, you know, as we talked about with revumenib, an important part of the paradigm for revumenib is to use the drug post-transplant. So you're talking to those same physicians for both assets.
Got it. Just one last question, maybe just for the next 12-18 months, what are some of the key catalysts and milestones we should be watching for?
Yeah. I mean, a big thing will be the launch, and the ramp up, the submission and approval of NPM1, the expansion beyond relapsed/ refractory disease into other combinations, front line, and even in relapsed/ refractory, or sorry, the expansion beyond monotherapy relapsed/ refractory into combinations in the front line and even relapsed/ refractory patients for revumenib, potentially expanding into other indications. For axatilimab, we have an IPF trial ongoing. So a readout there could be really impactful as well. And, you know, we'll continue to do our diligence and look for other assets to build the company.
Okay. Great. Wonderful. Well, with that, we're out of time. Thank you so much, Anjali, for.
Yeah. That was really fun. Thanks for the conversation.
Thank you. Thank you, everyone. All right.
Is that the start of your day?