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

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, with us today. So Anjali, welcome.

Thank you, David. It's a pleasure to be here.

Great. And so 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 therapeutics.

Yes, 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 26. So soon to be 2 approvals. This is our hope. Both of these assets are first-in-class, best-in-class molecules, targeting multibillion-dollar opportunities in their initial indication. And we see significant development opportunities beyond that, and we've started trials in areas to move both products up line 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. And so we believe we are funded to 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 dataset that we can file with the FDA through a supplementary NDA in the first half of next year. And so it could have a second potential launch in 2025. And yes, we're just excited with where we are and what's in our future.

Excellent. Yes, great. Many interesting near-term catalyst milestones to watch. Of course, the near-term one that everybody is looking at is going to be the revumenib approval for the FDA approval in December 26, as you mentioned. I think the Street already expected pretty much an approval for this one. But I think there are some questions around this label. So maybe just help understand what the label is going to look like. What's the expectation for the label here, Anjali?

Yes. I mean I think the label is going to be very consistent with the population we treated the indication, the relapsed/refractory population. And so I don't think people should expect any surprises, but I think it will be very on par with other labels in this space.

Got it. And what about things like black box warning, QTc prolongation? Any thoughts around that as well?

Yes. I mean I don't want to go into too much detail. We are currently in active discussions with the FDA. And as I said, our approval is coming very shortly. But 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 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 there shouldn't be any surprises to the label overall.

That's right.

Got it. Great. And of course, the launch, everybody is looking at that as well. So ahead of launch, can you just tell us about the commercial ramp and the commercial preparations that you're doing right now?

Yes. 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 number of very experienced reps. They have, on average, 20 years under their belt in this space, 6 prior launches. They've got significant networks already built up. And so because they're on the ground, they're out there talking to physicians, profiling the accounts, making sure we understand diagnostics process, the pathology, the systems of care, what physicians need in order to seamlessly prescribe and address their patients. And so it's given us even more time to be ready to go. And I think 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 support for use and physicians understand that we're here to help them through this journey. So yes, it's been in place and they're just waiting for the green light from FDA.

That's excellent. So maybe just help us understand some of the initial expectation on the launch. Maybe what have you heard so far from physicians on the overall receptivity for revumenib in KMT2A AML? And what do you think the ramp is going to look like over the first few quarters?

Yes. I will tell you, I've been in this industry and worked in sort of the forecasting space 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 this is a very young patient population, unlike most AML, 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 in the trial experience where it was later-line patients, we're 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 -- lower the risk of relapse as much as possible, which includes putting them back on revumenib after transplant because of the tolerability profile, 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. There's a couple of things that have changed versus the other targeted therapies that have launched in this space. So when the IDH inhibitors and FLT3 inhibitors first launched, that was the beginning of targeted therapy. And so identifying the genotype of patients was new. And I think over that time, it's become very standard. Even the ability to diagnose and identify patients has become easier and faster. So that dynamic, I think, isn't 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 dataset in relapsed/refractory NPM1 patients. And 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. And we can manage patients as we need to with revumenib and feel 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 frontline. And I think all of that data is -- we're going to have some updates at ASH next month, but all of that evidence is really compelling to physicians. And I think it changes the trajectory. It's not launching just for one indication, one patient population. And so I think we're really excited. We think it's going to be a really strong launch. And as I said, we have built a really strong team to make it happen.

Yes. No, that's great. What about the duration of treatment for revumenib in KMT2A? What does the number look like for the duration of treatment?

Yes. Right now, our estimate is about 9 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 2 categories. I mean obviously, responders and nonresponders. The responders, as I said, was about 2/3 of the patients. Because for physicians, what's important is clearing the tumor burden. And that was -- that includes measures beyond CR/CRh, so getting the CRi, CRp or even MLFS is important because all of those metrics indicate a clearance 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 decrease the risk of relapse. So that could really extend the duration of treatment significantly. And right now, we're estimating 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 3 years post transplant. We've seen -- there will be some patients that 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 1/3 of patients that responded but didn't go to transplant. It looks like median duration in this third-line population we treated was about 8 months. And then we have the nonresponders that are about 3 months, and so that averages out to about 9 months overall. I will say, 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 line, maybe more patients can go to transplant as well as being able to keep them on therapy longer. So that's where we are today. We'll see -- we'll be monitoring in the real world how things go.

Got it. That's a really helpful commentary here. And maybe just for the audience here, tell us anything about the KMT2A market. How big do you think -- do you estimate the market is?

Yes. We think the total addressable market for KMT2A is somewhere around $750 million in the U.S. alone, and that's based on sort of the duration of therapy, which we just talked about, the epidemiology of these 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 and $40,000, and that's substantiated by current therapies that are launched and on the market. And so 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. And we've seen with other targeted agents in oncology, it isn't a surprise to see these agents owning 85%, 90% of their market. So we think we have a really great place to start. And then as we talked about NPM1, we'll further expand the potential value in relapsed/refractory. And then we are looking to go into frontline and make sure revumenib becomes almost the backbone for these patients with KMT2A and NPM1 mutations.

Yes. 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.

Yes. 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, with the exception of one, have suggested they're seeing. 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 we think we've produced another approvable dataset. And as I said, we'll look to submit an sNDA in the first half of '25. But just to reprise the data, we saw an overall response rate of 50%, 64% of those patients were MRD negative. So deep durable response -- deep responses. We saw a duration of therapy of -- 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. And I will emphasize that the population we're treating here with NPM1 is a much older patient population. So 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. And I think those are reflected a little bit in minor shifts in the safety. But overall, we think this drug has performed very, very consistently. We know and predictably across both patient populations.

Got it. Yes. 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. The expectation was around close to about 30% because of the competitor from Kura, ziftomenib. And so maybe just help level set the 23% CR/CRh and the ORR and duration of response in terms of what it means for the patients here.

Yes, sure. Sure. So -- and also, revumenib had put out a 36% CR/CRh rate in Phase I as well. So 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% to 36%. So it 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. It's a matter of a couple of patients to get to 30%. And is that a meaningful difference? I think that's questionable. What -- and again, I would say we've tested over 300 patients in our entire monotherapy experience, and 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% to 60% range. And that is what physicians focus on. Really the one thing you want an antileukemic 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 2 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. Venetoclax has been an effective agent in AML, and it was initially approved at the -- an accelerated approval at the end of 2019. And so through the course of us developing menin inhibitors, physicians have also gotten more comfortable using venetoclax in their population. So we -- 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 for physicians that we've talked to, they have wholeheartedly been so excited about this agent. And it's not just 1 point estimate that means the drug is effective and exciting for them to use, it's the totality of the evidence. So the safety is very manageable. We had a thought leader, Dr. Eytan Stein on our call, and he's been very involved with the development of many targeted agents in AML. And 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 -- he's actually said on a call that he tells us -- tells his patients, the side effect is you're going to feel better. 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. Yes, no, that's really helpful commentary. Just regarding that 75% prior ven 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 ven? 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 CML, and then it's moved into AML at the end of 2019. And that was an accelerated approval. The confirmatory trial read out, I think, early 2021. And I think that data that they generated was very strong in AML, and it treats a broad population in its frontline in the unfit -- it was significant improvement over azacitidine alone in the unfit population. And physicians have learned to manage some of the issues with them, namely the cytopenias, by changing the dosing frequency from 28-day cycles down to 21, 14, and in some cases, even 7 days to get to a very similar efficacy and mitigate some of the safety issues. So I think with all of that evidence and experience, ven has become more and more of a standard of care, even to the fact that there are some interesting trials going on to see if you could displace chemotherapy with venetoclax-based regimens in the fit population and still get to similar efficacy. I think there has been a slight lag in uptake of ven 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 ven 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 ven. And we feel like that is what physicians want to do, and it is the best thing for their patients.

Got it. Yes. You alluded to the -- some of the safety things we saw. And I actually received an email question just regarding that safety. And the question asks, when the FDA makes a 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?

Yes. 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 -- we're under 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 in 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 we 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 sBLA -- or sNDA filing they plan to do in first half '25, how soon do we think we could actually potentially get an approval? How fast will the review time line look like?

Yes. 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 6 months. But depending on do we get priority review, do we do BTD, all these things, it could shift how much time FDA spends on that quickly -- to review it quickly.

Got it. And then based on your experience with the KMT2A filing, I would imagine you've already have that experience like expedite the filing process, right, getting to get all the package. So 6 months, I think that will make sense. So the second half 2025, that's when we should be expecting.

It's possible. Yes. I think we'll give more guidance when we have a better sense of when the package goes in. But yes, it's not -- definitely not out of the options.

Great. Now we have about 6 minutes left. I do want to touch base on the -- on your second program, Niktimvo, which is quite interesting. And recently, you closed a deal with Royalty Pharma, $350 million for 13.8% of the royalty from Niktimvo. So just help us understand the structure and the process that went through to actually ultimately get that deal there.

Yes. No, 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 the 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 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 you're right, it's a 13.8% royalty on overall revenues. We share axatilimab or Niktimvo with Incyte Pharmaceuticals at 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 2.35x 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 frontline 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. 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, and I think annualizing over $500 million in the third full year of sales, which is really impressive. And we don't see why axatilimab or Niktimvo would be any different. 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 incidence of death in this -- and organ damage and death for these patients. And so bringing this in as a tool for physicians could really change how GVHD is treated and even the progression of disease. And 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 the anti-fibrotic access, as I said, also plays an important part in many other diseases. So yes, 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. Got it. And so just ahead of the launch, any kind of thoughts around the commercial preparation? And between you and partner, Incyte, who is going to be driving most of the commercial ramp for Niktimvo?

Yes. 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 major drivers for us to do this deal. I think it gives -- reduces a lot of hurdles on patient support and access to physicians and potentially speeds up the ramp to adoption. But it's not a huge field force necessary to address the physicians that will be making decisions on 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 we feel like the footprint we've built for revumenib totally encompasses what we need for axatilimab. And it gives our reps something -- 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 2 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 the percentage of reps that will be detailing axatilimab will be shared with the Incyte P&L, so yes. And as we talked about 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 to 18 months, what are some of the key catalysts and milestones we should be watching for?

Yes. 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, frontline and even in relapse -- sorry, the expansion beyond monotherapy relapsed/refractory into combinations in the frontline 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 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.

Yes. No, it was really fun. Thank you for the conversation.

Thank you. Thank you, everyone.