Good afternoon and welcome once again to TD Cowen's 45th Annual Healthcare Conference. I'm Phil Nadea, a Biotech Analyst here at Cowen, and it is my pleasure to moderate a fireside chat with Syndax Pharmaceuticals. We have with us today Michael Metzger, the CEO; Steve Kloster, the CCO; Keith Goldan, the CFO; and Sharon Clary from IR is behind the pole, but she's right up here. Hand it over to you guys. First, can you give us a brief state of the company overview, biggest strengths, biggest challenges, and what do you need to do to create value over the next 12 months?
Yeah, thanks, Phil. Thanks for having us. It's always great to be back at Cowen in Boston. Look, it's a really important time for Syndax. Probably not great news to anybody, but we have two approved products, and we recently got them approved last year, and now we're launching. We're in the midst of a launch phase, really exciting time for the company, and we're off to a great start. Yesterday, we reported our first sales for Revuforj at a good partial quarter.
Talk about that today. That's a big strength, right? We're one of the very few companies that have two approved products and are in the launch phase. Really very unique and exciting times ahead. That's our, I would say, our biggest strength, and we have to just execute. That's the key to our success this year, executing not only on these two product launches, but also expanding the use of our products, going to additional trials to expand the utilization. We know what's in front of us, we know what we have to do, and the good news is that we have the resources to do it.
Maybe starting with the Revuforj launch, can you give us an update on how the launch is progressing and briefly review the metrics that you gave during yesterday's Earnings Call?
Sure. Maybe I'll turn it over to Steve. He'll talk a little bit about the launch.
Yeah, absolutely, Thanks, Michael. We did report net sales, as Michael suggested, of about $7.7 million in the quarter ending December. About a third of that was inventory. We also provided on our earnings call yesterday more color about the launch. No patient numbers, TRx volume for a number of reasons. It's early, we don't have a complete picture on data, but we did provide a perspective really through February.
That is about three months of launch, and one of the main goals at the start of a launch is getting a broad foundation of usage. We call in about 2,000 treatment centers. Our customer-facing team does. We've prioritized the top 200 accounts. These are the medium to large-sized academic institutions. They collectively cover about 2/3 of the patient opportunity, and about 33% of that 200 has since prescribed. We believe that's a good start.
Many of those counts have ordered more than once, whether that's for another patient or for a refill. Broader than that, we're obviously getting utilization outside that 33% within that top 200. Things we like to look at in a launch, that broad foundation of use. We've seen community oncology begin to prescribe. That's great. Very early in the launch of a drug for that to happen. We think it speaks to unmet need in the space, speaks to the ability to identify patients with a KMT2A rearrangement, relapse refractory, acute leukemia, and it speaks well, I think, to the product profile.
Efficacy data, that's compelling in the profile. Safety and tolerability, that's well understood. Dosing, that's very clear. On the academic side, in addition to the big institutions, even the smaller ones have written. Good start, and I think what also suggests is that there's more opportunity since there's still more accounts that have to get online.
As we look to future quarters, what metrics can we expect you to provide? Obviously, you're going to be giving revenue like you did this past quarter. What else do you think you'll provide for investors on your quarterly calls?
Yeah, beyond that, I mean, the percentage of the top accounts that have been prescribing, that's something we'll update. We have another earnings call in a couple of months. We'll give an update there. Certainly, other metrics around managed care formulary coverage. We also did share this yesterday. We're at 53% coverage, which is great at month three.
More importantly, we're seeing claims being adjudicated through the medical exception process in advance of formulary coverage. We've seen claims through the Medicaid side of the business, Medicare Part D, as well as commercial. I think as things evolve, we'll be able to go broader, obviously, than those metrics as data becomes more clear. We do have a limited distribution network, but we don't have visibility into all of it. We really have visibility into some of it. Some of that will evolve, and as trends develop, we'll be able to share more of that over time.
Are there warehouse patients? Do you have patients in early access programs, compassionate use, clinical trials that you can convert to paying patients quickly, or is this more of an incident market where, because life expectancy isn't long, when patients are newly diagnosed, that's when they're going to go on through?
Yeah. Good question, and you're right, Phil, this is not a place where there's warehouse patients or what you consider a bolus. Patients, they're just too sick. They're not waiting for the next treatment. However, there is a dynamic out of a launch like this in targeted therapy. We saw what is probably going to be the broadest population of patients treated simply because you have patients that first relapse, which is where the drug is, that's where it's indicated for. It's ultimately going to be used there more.
There was some of that use at launch, but we also have patients that were essentially on hospice, brought off just for one last option. Specifically with EAP, we had less than 10 patients that transitioned over, so that's really behind us. What we'll be seeing moving forward is really true patient demand.
The 200 hospitals that cover 2/3 of the patients, I assume that's your highest priority for initial use. Is that where you're focusing all your marketing efforts?
Definitely not all of it. I mean, I think you want to capture the whole patient population, and you need to go to all 2,000 treatment centers. We've got a sales team that is as big as any large pharma would put into place. We've got different customer-facing roles to call in the whole audience. We call in the whole audience, but we do prioritize the top 200. More sales calls to those institutions, more of our non-personal effort goes to those institutions.
One of the things we often say is no patient left behind, and that drives where we are, where we are to be there. We've also invested in some technology that allows us to take diagnostic lab data. We turn that through some artificial intelligence machine learning just to predict where the patients may be. We obviously don't know patient names, but we're able to deploy against those opportunities as they occur.
Can you remind us of the payor mix? Commercial versus Medicaid versus Medicare?
It really depends on the KMT2A rearrangement suggests a younger patient, so that's going to skew more towards commercial. There'll be some Part B, D business, and of course, some Medicaid. NPM1 mutation, which we know we produce data, that is something that we'll look to later this year, hopefully get approved in that indication. That'll skew more towards Medicare Part D. What we've seen early that's encouraging is that, again, we've seen claims through all three of those channels. The mix will change just depending on the age of the patient, essentially.
Can you remind us how Syndax has quantified the revenue opportunity in relapse refractory KMT2A?
Sure. We see it as about a $750 million opportunity in relapse refractory alone, again, just for KMT2A, relying on about 2,000 patients. AML, ALL, about 10% of the population is KMT2A. If you think about the drivers of a TAMs in this market, it is number of patients, 2,000. Price for the drug per month is about $40,000 a month, and we're estimating about nine months of therapy across the different patient experiences. You'll have about 2/3 of patients who respond. About half of those patients stay on drug for about eight months.
About another half go on to transplant, and a good portion of those, according to physicians, and what we've experienced, the vast majority of those patients go back on therapy in a sort of maintenance setting, and that can extend for months. We've seen patients out for three years on our drug in a maintenance capacity. That's a little bit of an open question, but across those three different experiences, or two different experiences, and then you have patients who about a 1/3 in our trial didn't respond. Again, these were tested third and fourth line patients, so these are the sort of the worst of the worst, unfortunately. These were the outcomes. If you think about that and you average across all of the different segments, it's about nine months of therapy. Nine months of therapy, $40,000 a month, 2,000 patients, that's about a $750 million market opportunity.
Moving to NPM1, can you briefly outline the data that were presented, the pivotal data that were released last fall and presented at ASH?
Right. So this was a pivotal data set in our AUGMENT trial. We had 64 patients that were in the protocol. We actually extended. We had additional data that was presented in our event at ASH. More patients became eligible. We had over-enrolled the trial, so 77 patients in the efficacy evaluable population. The CR/CRh rate was 26%. Overall response rate was 48%. The data set that we'll be submitting to the agency will include all of the patients, so not only the patients that were in the 64 original in the analysis that was done where we hit the endpoint, but also the additional patients that takes it to 77. That's basically the entire data set. The overall safety was very good on the drug.
I think the overall response rate, sorry, the overall duration of patients was 4.7 months as we updated the data set from the original 64 to 77. That stayed the same. We think this meets the mark, not only statistically significant, but also clinically meaningful for these patients who importantly had failed a lot of prior therapy. VENCLEXTA was given to about 3/4 of these patients, and these were very good outcomes according to the physicians. When they looked at the data, they were quite pleased with the outcome. We think this drug will support approval, or this trial will support approval. We expect to submit it to the agency in the Q2 and hope to get the drug approved in NPM1 before the end of the year.
Any update on the timing of publication of the data?
We will submit for publication, and the significance being we expect to submit for publication, which would allow us to then in turn submit to guidelines. If you have an approved drug, you're able to submit to guidelines once the data is published. That is what we will do in the Q2 , and hopefully access the guidelines in the Q2 as well. As I mentioned, you can get the drug approved fully before the end of the year.
Can you discuss the speed of uptake in NPM1 patients? Do you think the data that you have is sufficient to make it standard of care in relapse refractory NPM1, and how quickly will it be adopted?
Right. So yeah, I think it's certainly sufficient. It's certainly sufficient to, and nobody's shown better data in terms of NPM1 patients. It's a robust data set, as I mentioned. We do think that uptake will be swift. There is high unmet medical need in this population, and certainly in the relapse refractory population where outcomes are poor. We're the only menin Inhibitor on the market today.
We are for KMT2A. We do know that physicians are excited to use the drug, not only for KMT2A, but for NPM1 and in combination and other settings. This will be the start of what we think is a wave of use, and we're already starting to see, and there's some anecdotal use of the drug being used that way even without a labeled indication. I think it's a very good start for us, and with guideline support, and then an ultimate approval, I think we should be dominant in the relapse refractory setting.
We did an ASH investor event with some leukemia physicians, and they thought that they could use Revuforj in some of their NPM1 patients immediately upon approval on KMT2A. Do you know if that's happening?
Yeah, as I mentioned, we believe it is.
You believe it.
We can't quantify that at this point, but we hear anecdotally there is some use.
How much will that open up once, or how much will reimbursement access open up with the NCCN guidelines? Will all patients then have access, or will it still be somewhat of a minority?
Yeah. You want to take that?
I think from a payer standpoint, payers, we do not get full visibility on claims in terms of the mutational status, but we believe there are already paid claims for NPM1. Obviously, we are not promoting it that way at all, but anecdotally, it is happening. Payers do look for support, whether it is peer-reviewed publications or NCCN guidelines, i t will just give them further confirmation that it is okay to pay for these claims. They recognize the unmet need. We are talking about patients that have no treatment options, and I think the success we have had in formulary coverage overall shows that payers understand that. They do not want to stand in the way of a patient getting appropriate treatment.
How does Syndax quantify the revenue opportunity in NPM1 AML?
Right. So a very similar set of metrics, where the price is the same. I think it's about 30% to 35% of AML is NPM1. So if you apply that math, it's about 3,500 to 5,000 patients in the relapse refractory setting. So at about eight months of therapy, $40,000 a month, and that range of patients, it's somewhere north of a billion dollar opportunity in relapse refractory. We think it's somewhere a billion to a billion and a half.
Moving to the front line, what's the status of the planned pivotal trial in unfit first line KMT2A and NPM1 acute leukemias?
Right. We are starting a trial with the HOVON group. We've talked about that. It's a trial in newly diagnosed patients on top of VENCLEXTA. It's a randomized trial, and this will be started this quarter. Exciting, probably the highest unmet need in front line for patients. It'll be driven by NPM1 patients.
There will be KMT2A patients included. The statistics are driving off of NPM1. We will be the first, we believe, to have an indication. It's a global trial, global registration trial. We haven't given a timeline for completion of that trial, but we expect to be the first to have an approval there. As I said, highest unmet need.
Certainly, we've shown data in the BDAML trial that's quite compelling, 100% response rate, 95% MRD negativity, just a really good profile in combination with VENCLEXTA . That sets us up with the proper dose and the right orientation to start our pivotal trial.
What are your thinking on the endpoints for the pivotal trial? Is there a possibility to file for accelerated approval on a CR endpoint, like one of your competitors is planning to do?
Right. I mean, look, I think there's some precedent for CR as an accelerated approval endpoint in that population. That's not news to anybody, I think the VENCLEXTA experience, or I should say the VENCLEXTA experience, then was approved in that capacity as an accelerated approval and proved its point and got the overall survival endpoint as well. I think that pathway is possible and something we'll avail ourselves to. We haven't really talked about accelerated endpoints.
I think we've always been a little bit more careful in terms of our regulatory interactions, and so we'll choose to hold those back. I think it's a reasonable assumption that some options for accelerated approval would accrue to us as well. I think our competitor talks about it in a different capacity than we do, but we're set up, I think, for success in the front line setting, including anything that would be available to us as an accelerated endpoint.
What are your plans for other trials in the first line or maintenance setting? For example, trials in combination with SEMP+3 in the FIT population or FLT3 inhibitors , or just generally a maintenance-based regimen. Any plans to move those?
Yes. We have plans for several trials that will start in 2025 in the FIT population. It's not a one-population trial, right? We're looking at the different segments, being a little bit careful about how we reveal that. Over time, as the year goes on, you'll start to see those trials get stood up. Some will be registration-directed, and some will be guideline-directed. The timelines will vary and the idea here is that we want to generate the most data as quickly as possible to be able to kind of leverage our opportunity in that setting or in those range of settings. Really, we're the first drug approved and have a great profile there. We have done work with chemotherapy. For instance, we completed a trial with FLA, which was a couple of years ago in the making.
We presented that data, and it's very positive. We have a good understanding of dose. We're completing our phase one work, testing a few doses in combination with IC, and that will be available in the second half of this year. That dose will feed into, or the range of doses will feed into our trials in the FIT population. I said yes because we are covering, we expect to cover the range of opportunities and options in the FIT setting, just not in one trial, probably multiple trials.
Got it. Okay. How do you assess the competitive landscape for the menin inhibitor class? At ASH, there were data from at least three other menin inhibitors. How do you think Revuforj is going to be differentiated?
Right. It's always good to be first, and I think we have a profile that will stand the test of time, first and best. I think ultimately, having both indications, being first is very important. I mean, I think that's key. You have to be first in oncology. I think that's a known thing that you have the opportunity to really spend time with physicians and give them the kind of customer experience that they can relate to, they want for their patients. We help identify patients, get them the drug quickly, and get the drug paid for, and everything in between. I think that opportunity to provide that service for a year plus in advance of any potential competitor is a big deal. It's a very big deal.
Beyond that, we'll have both indications for KMT2A and NPM1. Our nearest competitor will not. Remember that for KMT2A, it's AML, it's ALL, it's adults, it's pediatric. We have multiple doses. We're trying to cover the entire landscape and really address all the patient needs. Look, I think we have a head start, really good head start. A year might as well be 10 years as we're building this.
We're going large with our field force and deep, and we have lots of experienced people who know how to do this, and we're off to a great start. I think that speaks volumes, and we'll have both indications, and ultimately, we're going to exploit the whole opportunity by getting to front line first and availing ourselves of any kind of acceleration that's open for approval. We're, I think, taking a very nuanced but aggressive approach to building on what we've already established.
How would you quantify the revenue opportunity in the first line and maintenance settings?
I think we said that the overall market opportunity is $4 billion plus, t hat might be larger. It sort of depends. The biggest lever on the market is likely to be duration, right? Duration of therapy, how long they stay on. I think that's a little of an open question. We've said $4 billion plus, and that assumes greater than a year of therapy in front line.
As we know, I kind of laid it out in the relapse refractory setting. As the front line grows, the relapse refractory market will get smaller, but it could be $4 billion, $5 billion, $10 billion, even larger, depending on how long patients stay on and how impactful maintenance is. We believe maintenance will be a big deal as patients go through chemotherapy and stay on potentially Revuforj for a long time, perhaps many years. It could be.
We've seen that with our therapy. We're also seeing patients get transplanted, which you expect less of this, but you see patients get transplanted in the front line, right? What we've seen in BDAML, for instance, 10 patients got transplants. That's high. That's a higher number than you would expect. The ability to transplant them and put them back on drug and perhaps keep them in remission for a long period of time, that's sort of the vision for the market. It's a little hard to answer how big that could be, but certainly, I think $4 billion plus is a reasonable estimate.
Do you have any desire to partner for commercialization in any regions of the world?
It's a consideration for outside the US I think there's a lot of interest, obviously, partnering with us. I think we're very well situated in the U.S. to develop the drug in a multiple capacity and looking at front line trials, but also really launch it with excellence. We're doing that already. I don't think we need help there. I think US, we don't have a commercial organization, so it might make sense at the right time to bring on a commercial partner to help us with that.
Our priority today is to make sure we stand up and do the best job we can in the US to launch our two medicines, which I think we're doing pretty well, and develop them and do global trials, as I laid out, to exploit the opportunity. A partner is a consideration down the line, yes.
One last question on the menin program before moving to Niktimvo. What do you have behind Revuforj in development? Are there next generation candidates that you're moving through clinical development?
We haven't been public about any of that. I think, look, we're leaders in this space. We understand the biology very well. We're excited about other opportunities for Revuforj, perhaps in solid tumors and other areas. There may be more to do in menin. I think we're certainly excited about that, but we haven't publicly talked much about that at this point.
Great. Moving to Niktimvo. Can you give a brief update on the launch?
All right, Steve, do you want to?
Yeah, happy to. We know the drug was initially approved in August. We had two new vial sizes that needed to be approved t hey were in January. We are about a month in market, w e do co-commercialize this with our partner Incyte. They are a great partner. They have basically created the chronic and acute GVHD space. We have overlap in our call panels, so we participate in the co-promote. It is really too early to suggest how the drug is doing. I think what keeps us confident that this is going to be a large drug, you have got significant unmet need in the population p atients are highly symptomatic. There is a good analog in Jakafi, which we know has been in the market for about three years, annualizing it. Now we are over $500 million a year and growing in double digits.
Niktimvo is at a premium to that agent. We think Niktimvo will grow the market. This isn't a matter of one drug or the other. This drug could be used on top of what's out there, whether it's Jakafi or Rezurock. We feel good. Good start. At our next earnings call, we'll be about three months in and obviously provide a lot more information at that time.
What trajectory do you expect Niktimvo to follow? Is Revuforj a good proxy? Is there a reason to think Niktimvo could go faster or slower? How do you consider the trajectory?
It's a good analog. I mean, I think three years, $500 million, that's pretty good. We think that drug, and most believe the drug's going to do well over a billion. Otherwise, if you wouldn't have purchased it from Kadmon, they've put a few more resources against it. It's the kind of space you don't need to, you don't need a lot.
I mean, this is, we talk about 2,000 treatment centers to support Revuforj. It's a fraction of that for GVHD, t here's maybe 150 transplant centers of any significance in the country, and the top 35 generate probably half the patient volume. Very focused effort. Because the drug was approved in August, there's a little bit of likely pent-up demand out there, some EAP transitions. There's different dynamics. Patients tend to stay on therapy for long periods of time, in excess of a year.
We have patients in the clinical trial that are there probably for five years. The drug's well tolerated. Patients tend to stay on treatment as long as it's hastening deterioration in many cases because there's not a lot of options. The drug is indicated for third line. It's fine if it stays there. It could be before or after Niktimvo. We'll see on the ramp, but we've got decent expectations.
What do you think will be the biggest barriers to uptake initially in the launch? Will it be physician awareness, waiting for patients to cycle off their current therapy? What do you think will be the rate-limiting factor to uptake, and how are Incyte and Syndax working to counter those impediments?
We talked about footprint and patient identification. Patients are well known, I mean, they're often treated at their place they got transplanted. Now, there are patients who, and maybe this could be a barrier, it's certainly the ability to be overcome. Not every patient lives by a transplant center, right? There are folks that may live in rural settings that may need other care. That may take a little bit of time to develop, but that's not in the way of anything long-term and certainly not in the way of uptake.
It is a buy-and-bill product, so this is a Medicare Part B. There are components to that, but the transplant centers that have infusion services, this is an IV infusion. They know how to do that. They know how to seek reimbursement. The drug already has a permanent J- code that'll be in effect as of April 1. You'll see a ramp that'll accelerate. That's just what will happen as patients come in and transplant centers and other IV-infused clinics get up to speed. The great thing about working with Incyte is they have a field reimbursement team, they've done all this before. I think for us to have two products launching, we can really focus on Revuforj, add support for Niktimvo, yet both products will be maximized from a launch perspective.
You mentioned Revuforj could be a billion-dollar product at peak. How would you quantify the peak potential of Niktimvo?
Yeah, I mean, I would say it's at least as big.
At least as big, yeah.
I mean, I think, look, we recently did a collaboration with Royalty Pharma. I think they see it as that big as well. I mean, I think multi-billion dollar franchise with extension, right? It is not just third line GVHD. It is in combination with earlier line therapy, steroids, as well as Jakafi. I think that extension really makes it a bigger, potentially a bigger product.
If you count IPF as our first indication outside of GVHD, it is a new mechanism there. We have had some really interesting clinical data that suggests that this drug could be really active in IPF. We are doing that trial now. We should have those results in 2026, so not too far away. If that is positive, then we will look to get the drug approved there. That could be a tremendous extension to this franchise. I think this is not just our view, but a view of our partners, that this could be quite a big franchise.
Can you actually dive into the Royalty Pharma deal in a bit more detail? What were the economics of it, and what was the rationale for doing it?
Sure. Thanks, Phil. In the Q4 , we sold a synthetic royalty in Niktimvo for a 13.8% royalty. The deal came to us. Royalty Pharma, we have relationships there, which is important in any transaction. We thought, in retrospect, given where the capital markets are, it's obviously, we think, a wonderful deal for shareholders. It allowed us at the time to go out and say for the first time that we believe we were fully funded to profitability, not needing to go back to the equity capital market. Given where we are in both launches and given the fact that we're fully funded today, it allows us to keep our head down, execute on two great launches, and execute on all the front line work that Michael laid out earlier.
What's the company's recent thinking on business development? Obviously, you have an infrastructure, but you are pretty busy with two projects launching. Can you take on another asset to run through your infrastructure, or is your plate full for now, and that's something they'll have to wait until the launches are more mature?
Right, I know our first priority is definitely the launches and the extension to these product franchises, which we talked about, the front line trials and other things that we're doing to make these products long-lived assets and successful. That is where our priority is. Business development is always important to us. We have a high bar for what we bring in. Looking at oncology assets, staying in oncology will be what we do. To the extent that we find and identify something that we think could add a lot of value, as we've done with Niktimvo and Revuforj, I think we will look to seize on those opportunities.
It's kind of good timing in the market to look at new options. Again, we're not going to jump or just add something to the pipeline to do it. I think it has to be quite special, and it's something we'll continue to pursue.
Perfect. With that, we are out of time. Thank you for the update, and thanks for coming to the 45th Annual Conference.
Thanks.