Good afternoon, everyone. Thank you for attending Jefferies Global Healthcare Conference. My name is , a senior biotech analyst on our biotech team here. Please join me and welcome CEO Mr. Michael Metzger, CMO Mr. Nick Botwood, and COO Mr. Steve Closter from Syndax Pharmaceuticals for this Fireside Chat session. Welcome.
Thank you, Kelly.
Maybe let's start with a high-level question. Last year, 2023, was a very exciting year for Syndax, with two product approvals back to back, and you're now transitioning into a commercial-stage biotech company. 2025 is certainly also a pivotal year for the company, as we look forward to many milestones, both clinically and also commercially. Maybe on a high level, tell us about your long-term vision for the company and where you see the company heading to.
Yeah, first of all, thank you for having us. It's great to be here with you. Exciting time for the company as we head into 2025, a transformational year for us, where we have two first and best-in-class medicines in markets where unmet need is very high. We are blazing our own trail here and building these franchises. We have the ambition and the fortitude with a great team, which we've built over many years. Now we have the team to take us to the next level, expand the business beyond the relapsed refractory markets that we're in today, and really go to the front line and build these franchises for many years. These are long IP assets, assets that will endure through up to probably 2040. We have a long life ahead of us in terms of building these franchises.
We are just super excited to get going here and do everything we can to bring more and more product to patients.
Okay. You have made fantastic milestones internally. At the same time, we also look at external factors and think about the outlook of any biotech company under the evolving policies on tariffs and also drug pricing. Maybe talk to us about your manufacturing, supply chains, and Medicare and Medicaid exposures, and how we should think about the impact on overall business for Syndax.
Yeah, I think the main takeaway is that we have very little impact on some of the things that have been discussed in the news, tariffs, what have you. I think the supply chains are robust and intact. We source ingredients and build our products in the U.S., manufacture final goods in the U.S. We see very little impact across the board. As I said, our products are domiciled in the U.S. in terms of IP. That is not an issue. In terms of our situation, I think we have probably some of the best. We are situated probably as well as you could be for these types of factors.
Okay. Let's dive into Revuforj launch, which is one of the key focuses from investors. Let's begin with the first quarter number. You achieved $20 million in sales, surpassing many expectations. Can you talk about what you have been observing in the second quarter or moving forward? How should we think about the launch trajectory for the whole year?
Yeah, thanks for the question, Kelly. I appreciate the way you phrased it, exceeding expectations for the first quarter. We're very proud of that. We have a great team in place and a lot of planning in order to execute against the launch. Really, three things that we think about that really drive launches, not just in the near term, but in the long term. One is the user base. We've got a broad and growing user base. Previously, we've talked about these tier one and tier two institutions, a couple hundred of the largest treatment centers in the country. Made a lot of progress there. Through March, we had estimated about 44% of them have written. That's going to be well north of 50%. One other thing about launches you need to cover is just the payer space. You need the drug paid for by payers.
Our formulary coverage has evolved very rapidly. We were just above 70% in March, and now we're north of 90%. The third thing that's important is just getting patients on drug quickly. We've got great specialty pharmacy partners, a great trade team, and we're able to get patients on drug, 80% of them within a week and some within just a couple of days. We compare that to other targeted AML launches. We're well above benchmark, which is great. It was a great Q1, as mentioned, from a sales and a demand perspective. Momentum is certainly building. We're looking to bring in new patients. That's really our primary goal, as well as getting patients, obviously, on continued treatment, but also, importantly, to get them to transplant. Because for KMT2A relapsed refractory patients, urgent unmet need, the goal is to get them to transplant.
We're seeing more and more of that every day and ultimately back on maintenance treatment. We think a good number in terms of market penetration into our primary market, we think we can get to over 50% in our first year, which would really be a great year.
Great. This first approval is in the KMT2A population. Could you maybe help us to understand the treatment duration average and in what range, and also any new learnings on some of the patterns with regard to how Revuforj is being used in practice? Is it also beyond the KMT2A population? How about frontline use as well?
Yeah, happy to take that too. I think the first part was around the length of treatment. We've talked about this previously in part of our TAM based on the clinical trials. We think long-term patients could be on, on average, about nine months. That's different patients, those who do not get a response, those who do, and obviously those who get back on transplant and then are back on for maintenance treatment. I think the expectation in this first year, it's going to be somewhere in the four- to- six month range. I say that because I think this is also part of the second part of your question, which is the range of patients and the type of patients that are put on treatment.
As you can imagine, as you enter a market at a point in time, you've got patients that are relapsed refractory with KMT2A rearrangements that really span the spectrum. You've got patients that are newly relapsed refractory. On one end, we'll call them first relapse patients. On the other end, you've got patients that are very, very sick. They're very deep into their treatment journey, heavily pretreated, later lines of treatment, and some were brought off of hospice. The range of success, let's say, in that broad patient population is going to be a little variable. What we're going to see, and we're already seeing this over time, physicians are telling us this, we can pick this up in the data, that patients are moving earlier, right? First relapse, which is where the indication is, that's where the intent to use is.
Those patients will have better treatment success. Again, likely getting a response, going to transplant, and the assumption, because physicians tell us this, the intent is to put them back on treatment. That is almost universal amongst all hematologists and transplanters. That is where we are at.
How is the real-world experience of using Revuforj different from clinical trial experience?
I think some of that is in the question I just answered in a sense. Now, the trial had patients that were heavily pretreated, much later-line patients. The results in the trials were quite good, right? About a quarter of patients ended up going to transplant. I think what we may see, and it's early to tell, but I think these are things that we're hearing from physicians. We were just at ASCO, which I know some of you folks may have been at. We had an advisory board. Ten of the leading hematologists in the country are telling us the success that they're having with the drug. As it relates to that versus clinical trials, I wouldn't be surprised if, frankly, we see better results in the real world compared to the data set that formed the basis for registration.
Given this is the first-ever approved drug for this very hard-to-treat population, I think it's safe to assume physicians and patients are very enthusiastic. If your sales team ever receive any pushback, what could be the reasons?
Yeah, great point. I mean, I think urgent unmet need, Revuforj is quickly becoming the standard of care for this population. You think long and hard, what can you expect in the marketplace? We've got a great label. We knew that as the label got approved. More importantly, what we're seeing in the real world is side effects that are consistent with the label. Physicians can certainly manage it. There's nothing keeping them from getting patients on drug. The dosing is incredibly clear. Side effects are well documented. The treatment teams at any institution, it's not just the hematologist. There's nursing support care. There's PathLab. There's other folks. We've got a customer-facing team, nursing staff. We've got an ample medical affairs team that can answer any questions. The early experience has been, I would say, excellent.
There's nothing keeping patients from getting on drug, whether it's something within the profile, something that payers are throwing at them. No obstacles. It's really finding patients and educating physicians. We've been able to do both pretty successfully so far.
Great. Also on the safety front, how physicians are managing, for example, QTc prolongation and also differentiation syndrome, it cannot be avoided given that's part of the actual mechanism of action and how physicians actually give you feedback.
Yeah, good question. It's eyes wide open. You don't know what you're going to see once a drug is put into the real world. As mentioned, we're seeing what's in the label. You train to that. Hematologists and their staff are expert at caring for these patients. They're complex. Treatment is often intensive. Things like DS, it's eyes open wide. You need to know that it could come. If it comes, how to manage it. Physicians are able to do that with Revuforj. Same thing with QT, right? It's not uncommon. Whether or not you've got a drug that may cause QT, you're going to do an ECG. You may do some monitoring ongoing. With QT, you monitor it, you manage it, you move on. It has not been a hindrance at all to get patients on treatment or to keep them on.
So far, tons of success. That experience base is building each and every day. I think for some physicians, you often ask, how long does it take to get comfortable with a product? It is really two to three patient experiences. Across our user base, that is probably the average number of patients treated. That will only increase over time.
Great. Also, what percentage of the KMT2A patients also bear other gene mutations such as FLT3? How do physicians prioritize treatments with many inhibitors and also other targeted therapies?
Thank you, Kelly. Thank you for having us. Co-mutations are relatively rare in KMT2A. They're actually more common in NPM1, a subtype of AML. We've actually looked at that and explored it. FLT3 essentially comes in two variants. There's an internal tandem duplication variant and a tyrosine kinase domain variant. The ITD variant's a little bit more common. It actually has a slightly worse prognosis. Importantly, we've actually looked at that subset of patients in our AUGMENT study and actually found really quite good activity in terms of CR or CRh. In that subset of NPM1, patients responded really quite well to Revuforj in our pivotal trial.
Great. You recently submitted a supplementary NDA for MPM1 patient population. Tell us, how should we think about the review process and timeline?
Right. We did submit the sNDA in April. This is our, of course, a priority review would give us a six-month clock to approval. That clock starts at the time of submission. There is no acceptance period. You count from April, which puts us in the October timeframe, assuming that we have accelerated approval, sorry, priority review. That is different than an NDA where you have six months from the time of acceptance, which is two months after your submission is complete. We are first to market for both indications. We expect to be approved ahead of any competition on NPM1. Sets us up for success. Importantly, we will have guidelines, which hopefully the update to the guidelines for NPM1 as well, which we expect before approval, very important for the overall trajectory of the drug.
Are you able to narrow down the timeline for NCCN inclusion?
Yeah, it's a good question. We did submit. The first step, of course, is to get the data. Then you have to publish the data. We published the data in Blood, which was fantastic. Then we, of course, had the submission right away. Once it was published, we got it into the guideline committee. It is on a certain timeline. They can update the guidelines coming out of their meetings at any time. We do expect or have the expectation that it'll be included before approval. That could be as early as this quarter, as I said. There is opportunity beyond their meetings if they want to do an ad hoc meeting as well. We think there's plenty of opportunity to get it in before approval.
I think that's really important to our overall strategy to get the utilization to where we expect it to be.
I think we have heard anecdotal use from physicians, actually, in NPM1 patient population after approval. And so how should we think about this dynamic change quarter over quarter for the rest of the year for NPM1?
Yeah, look, I think NPM1 is a small percentage of our business today. The way we'd like to describe it is about 90% of what we're seeing in scripts is on-label use, so KMT2A. The other 10% includes probably some NPM1 use and some combination use, maybe not only NPM1. It is a small percentage of our business today. We see the guidelines being a leg up to that utilization. It will be important because physicians practice the guidelines. It is also important for reimbursement. Our field medical team has the ability to use the publication, use the guidelines as an educational tool for physicians. That is very helpful. We do think utilization will go up when the guidelines come through. Likewise, we expect another leg up of utilization once we have the full approval.
The reason for that is because you can deploy all your commercial resources against the label, including field medical and your reps. I think that allows us to give us the full promotional power of what we can bring to bear. That will give us the optimal positioning, we think, towards the end of the year.
Great. As there is a high unmet need, there is more than one company developing menin inhibitors. At ASCO in the last week, there is some data update for the NPM1 patient population. I do not know if your team were there. What kind of feedback have you heard from physicians and how do you position Revuforj relative to other inhibitors for the NPM1 opportunity?
Yeah, we were certainly there. We had a great ASCO. I'll let Nick maybe describe some of the data.
Yeah, I saw the data. I was at ASCO. I mean, I would make the point, firstly, that we're the only approved menin inhibitor currently. We have a broad indication, obviously, covering the KMT2A population in both AML and ALL. That does also include a pediatric indication, which I think is very important. When you look at data for other menin inhibitors, I think our profile remains really quite compelling. I think it's a best-in-class profile, particularly, I think, when you look at the efficacy endpoints. Efficacy is incredibly important for these patients. They have a very short life expectancy. The physicians and the patients, they really want to get into some sort of response and give them the best possible chance of a durable remission and potentially get to stem cell transplant.
We will be updating our CR/CRh data from our NPM1 augment dataset at the EHA Congress. We'll be reporting out a 26% CR/CRh result, which hasn't numerically been surpassed yet. Perhaps even more important than that primary endpoint is the overall response rate, so the number of patients that actually have some sort of response. Our data is really quite compelling at 48%. That's really important for patients. Nearly half of the patients have some sort of response. We've actually just recently looked at how those patients do. We know we've reported a duration of response of 4.7 months, which again, I think, is a meaningful duration of response in this population. Perhaps even more so than that, we've actually looked at the overall survival in those patients that response. You get half of the patients into response.
The median overall survival for those patients is nearly two years. We've recorded 23 months. We'll be presenting that data in a congress in the near future. I think that's really important for patients. That's what we're hearing from the physicians. They're using the drug now. They like the profile. They very much like what they see.
Okay, great. Thank you. Super insightful. Maybe actually dig a little bit deeper on the MOA of menin inhibitors. Curious, how should we think about how does one menin inhibitor work in two respective different populations, KMT2A versus NPM1? In another word, if it works well in one population, can I assume it should be equally well in another one compared to a competing molecule? Or there could be some mismatch happens for two different populations. How should I think about the rationales behind?
Yeah, so the profiles are different from the drugs. That's clear. I think what I would guide you towards is AML that is driven through HOX/Meis upregulation. And what we've been able to show is that actually we have the broadest profile in terms of targeting that particular pathway. So we've obviously now got an approval in KMT2A. We've shown compelling benefit in NPM1. We've also shown good activity in other subsets of AML. To your question, that is driven through the same pathway like the NUP98r mutation, which is a relatively rare subset but is with poor prognosis. And we'll be presenting some data again at the EHA meeting showing that in a cohort of those patients, 60% of them get some kind of response in terms of a morphological remission.
In fact, one of those patients actually even went on to get a stem cell transplant and went on to maintenance therapy and was treated for 10 months subsequent to that at the time of the data cutoff. I think when you think about the different subsets of AML, up to 50% of AML could actually be targeted through that menin pathway. I think we're very well positioned in terms of the breadth of the profile that we've shown.
Fantastic. Now maybe moving to frontline combo, which are the next key step for menin inhibitor development. For investors not very familiar, could you actually lay out your frontline plan for clinical development, where you are at for fit-unfit patient population?
I think you asked just generally about frontline studies, correct?
Correct.
Yes? Sorry, I just wanted to make sure. Maybe just to describe where we are, because I think we have a leading position now moving into frontline combinations. This is a very important part of our development of Revuforj into newly diagnosed patients in combination with standards of chemotherapy. We are going to have a broad program spearheaded, I would say, by three randomized control studies to address the key population. Starting with the fit population, these are patients that tend to be either with a KMT2A mutation. They tend to be a little fitter, often a little bit younger, and candidates for intensive chemotherapy. We have a phase one program currently to support the tolerability and identify the dose in those studies that we are planning to report out in the latter part of this year.
On the back of those data, we'll have two randomized studies, one focused on the NPM1 population and one on the KMT2A population. We think that those subsets of patients are different. They should be addressed in independent randomized studies. That's what we're going to do. There'll be more details on the design of those studies towards the back end of this year. In the unfit population, and this is an attractive study for us, we're combining with venetoclax. We've seen very good synergies when you combine Revuforj, particularly with venetoclax. We'll be presenting some data at EHA from the BEAT-AML study, which is a combination looking at Revuforj with [veneza]. What we were able to show in that study is that we identified a dose that we can take into phase three.
Actually, that's the same dose as our currently approved indication, which is simple. We showed that it was really very well tolerated. There was a very low rate of discontinuations in that trial. Frankly, it showed very encouraging efficacy and activity, particularly when you look at the complete response rate and the proportion of patients that went into MRD negative disease, which speaks to the depth and the durability of those responses. In fact, in the cohort we studied in that trial, 100% of patients had MRD negativity and 67% had a complete response, which for those of you that are familiar with the Vialli registration study for Venn will know that that's a step change different from what was seen in that study, which gives a very good level of confidence in terms of technical success in winning in that study.
The EVOLVE study, which is sponsored by HOVON, we're working very closely in partnership with the HOVON study, is up and running. We have patients being enrolled. We have first patient, first visit. It's a large study. It's a multi-site international study. It is actively enrolling. As we have described before, it has dual primary endpoints. I think this is important because we're leveraging the data we've seen for complete response, which we know can be used as a surrogate. It correlates very well with overall survival. It has a complete response, dual primary endpoint with the potential to serve for accelerated approval. We will also be following that study for overall survival to confirm that. We're very well placed in the frontline setting. It's a priority for me and the team. We're accelerating quickly into that space.
More on the fit intensive chemo studies to come later in the year.
Very informative. Maybe two follow-up questions here. First, at EHA, do we expect a fresh data cut compared to abstract? Also, some proposed to use MRD inactivity as the surrogate endpoint for the accelerated path. Do you say, I mean, what do you think about that strategy and also any potential risks if we think about the timing of to do MRD inactivity testing and also how to think about stats design to show significance across control arm?
Should I take the first question?
Yes, sure.
Sorry, just to take your first question first. There will be some updated data you'll see at the EHA Congress in terms of some Kaplan-Meier around overall survival and other points, which I think is important to look at. Expect to see that. It's an oral presentation at EHA. Secondly, we are actively looking at endpoints that could also serve as accelerated approval. We have a number of collaborations ongoing with leading academic consortia supporting this effort and diagnostic work looking at minimal residual disease, both in plasma, but also importantly in bone marrow. We think it's very possible that if you can get more patients into MRD negative status, particularly using sensitive bone marrow tests, this is going to correlate very well with event-free survival and overall survival in the fit population.
We think exactly as we have built into the HOVON study that this could serve as an endpoint for an accelerated approval. More details on the design of those studies to come. I think we're well positioned with them.
Fantastic. I feel like I did not leave enough time for Niktimvo . You also beat expectation for the Q1 sales and marked $13.6 million sales. Maybe walk us through the launch dynamic you are seeing and how do you think about the potential moving to earlier lines?
Yeah, no, thanks, Kelly. We have some time to get to Niktimvo . It was a good quarter, stub quarter, a little bit of inventory component, but mostly demand. I think this is a market that is overlooked and probably unrecognized from an unmet needs standpoint. Patients with chronic GVHD need more options. It's a highly symptomatic disease. The impact on quality of life is very high. Patients can live with the condition for a very long time. I'd say the early take on the product that we hear from physicians, a welcome addition. It's got impact on fibrosis and inflammation, which are hallmarks of the disease. The drug, as we know, was approved in August. There was some period of time there was an EAP program. Physicians had some experience even before its commercial availability, which happened in the late January time frame.
Great response, meaning they really like what they see in the profile. Transplant audience is pretty small. There are just maybe 150 transplant centers of any significance in the country. At this point, nearly all have ordered, and most have ordered more than once. Good start, more to come. I think it'll be a surprise. It's being primarily used in the third line or later. That's where you expect it to be at launch. It'll move earlier. There are studies, as mentioned, as part of the question, a study with steroids and a study with Jakafi. Studies are ongoing. They'll report out in the near future. That'll move it earlier and really open it up. There are about 6,500 patients at any given time in the third line or later. The whole prevalent population is about 17,000. There's a lot of upside earlier in treatment.
Drug is really off to an outstanding start.
Fantastic. Can you also help us to understand the IPF trial? When do we expect top line data? How should we think about the competitiveness?
Yeah, thank you. I'm excited about this trial action. There are two reasons I'm excited about it. One is I think there's a compelling biological rationale in idiopathic pulmonary fibrosis why CSF1R might be effective. It targets macrophages and promyelocytic macrophages in two ways. One is both in terms of combating inflammation, but also fibrosis. This is very relevant in [idiopathic] pulmonary fibrosis. I think there are two reasons why you could see that effect biologically. We have already, if you like, proof of concept of that hypothesis from our AGAVE-201 study in chronic graft-versus-host disease. That, as you know, is a multisystem disorder. One of the effects of that is obviously in the lung. There is a syndrome called bronchiolitis obliterans syndrome, or BOS. We treated some patients with that in that pivotal registration study.
We saw really quite compelling both response rates and improvements in symptoms for those patients in the order of half the patients. Our MaxPIRE study is a randomized study actually looking at Niktimvo against standard of care with an FVC primary endpoint, which is going to be a measure of lung function and fibrosis. That would be the endpoint that if we saw a successful proof of concept, we would take into a phase three program. We hope to see those data towards the middle latter part of next year.
Fantastic. Michael, do you want to add something on top of that?
No, no.
OK. Maybe lastly, what investors should look for in terms of milestones from Syndax for the next 12 months? Quickly reiterate.
Yeah, sure. No, look, I think it's a, as I said earlier, transformational time for the company where we have data coming. Nick mentioned some of it at EHA with our NPM1 data being presented, as well as our combination trial with the BEAT-AML trial. These are important data sets both in relapsed refractory patients, but also in newly diagnosed patients. We have an sNDA that's on file. We expect approval before the end of this year, hopefully get into the guidelines. We expect to get into the guidelines as well. We feel we're set up for success to launch in NPM1, which is our second indication. We have obviously important performance ahead of us in KMT2A, where we're just ramping and seeing great uptake. We expect that to continue and build over time as that franchise really, as Steve mentioned, gets to 50% penetration.
We have a lot in front of us with these two franchises, Niktimvo as well. Same story, great launch off to a really tough, a strong start, excuse me, and doing really, really well. We expect that to build over time. I think the opportunity in front of us is to expand into frontline over time, build the data sets, build up utilization to best in class, first and best in class molecules. These franchises really can go pretty far. We are really excited with the team we have built to execute and put our head down and do everything we can to build value for this company. It is a really important year for us.
Allowed to anticipate a very exciting time. We're going to wrap up here. Thanks again for Syndax team for this great discussion. Thanks everyone for attending.
Thank you, Kelly.