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

All right, let's get started. Welcome, everyone, to the 42nd Annual J. P. Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Priyanka Grover; [indiscernible], Malcolm [indiscernible]. Our next presenting company is Syndax and presenting on behalf of the company, we have CEO, Michael Metzger. Michael?

Thank you, Anupam. Thank you, JPMorgan, for having us to this year's conference. It's always a pleasure to present to all of you today and give you an update on our progress. It's been a really very exciting year. As Anupam said I'm Michael Metzger, I'm the CEO of the company. So this is our forward-looking disclosure as others. We are making forward-looking statements today. I ask you to refer to our SEC documents for further information related to forward-looking statements. So I'll start off today talking a little bit about our 2 programs, actually, a lot about our 2 programs. We are, as many of you know, an oncology company with 2 near-term commercial heme assets. So our focus is certainly in heme. We have 2 potentially best-in-class, first-in-class and best-in-class hematology assets. The first is [ revumenin ], -- it's a novel menin inhibitor targeting KMT2A, acute leukemia as well as [ NPM1 ], mutant acute leukemia. Second drug is axatilimab, which is a CSF-1R antibody targeting chronic graft versus host disease. Both were highlighted this year at ASH. So we had a very good ASH meeting this year with both the [ plan area ] for axatilimab and the late-breaker for revumenib. It's also an exciting time for the company because we have 2 pivotal programs that are going to registration. We recently submitted the first application NDA for KMT2A, acute leukemia under RTOR, real-time oncology review, the opportunity, the first opportunity for indication there in KMT2A and NPM1 is quite large. We think it approaches $2 billion, and we'll say more about that in a little bit. In terms of axatilimab, we also submitted BLA with our partner Incyte at the end of the year. So 2 filings at the end of the year on top of one another, quite a feat for a small company. That also has -- axatilimab has a large market opportunity in third line plus chronic graft versus host disease with opportunity for expansion. So both drugs have opportunity for expansion, but their initial indications we think are quite significant. Both of these programs are franchises with long exclusivity out to 2040. So they're well protected assets. And the company is very well capitalized. We recently raised $258 million net and an offering at the end of the year, and I'll say more about that, but it does give us cash runway through 2026. So a very exciting time for the company as we progress to a commercial stage organization. So first, I'm going to talk a little bit about revumenib. It's our menin inhibitor, as mentioned. The first approval will be in adult and pediatric relapsed/refractory KMT2A acute leukemia in 2024, and we do see these opportunities for expansion. So a little bit about the market to start -- this is the -- this will be the first drug to address both KMT2A and NPM1 disease. They represent about 40% of AML and ALL. On the left, KMT2A is about 10% of AML and ALL -- probably the worst prognosis for AML and ALL patients. They have an overall survival of about less than 3 months in the third-line setting. So it's a very, very difficult diagnosis. And today, there's no treatment that really works with these patients. And then for NPM1, it represents about 30% of AML. These patients have about a 50% survival rate at 5 years in the early settings, but you have in the relapsed refractory setting, very poor prognosis as well. Again, it's the most frequent genetic alteration. The good news is that revumenib represent the first drug to address both populations. So what are physicians looking for in a new medicine to treat these patients. They're looking for a drug that can get their patients to deep, durable responses, MRD-negative responses, get rid of the tumor burden and then be able to put patients back on drug in the post-transplant maintenance setting. They have to deliver this with safety and tolerability that is meaningful to these patients as well. And now we know based on data that we have as both monotherapy and in combination that revumenib can deliver on this. It can deliver monotherapy results for KMT2A and for NPM1. These have been durable, and we've been able to observe the fact that the patients can go back on and stay on drug for months, if not years, we have patients out to almost 3 years in the post-transplant maintenance setting. So the results have been very good as a monotherapy. And then recently, we've shown patients have done very well on combinations, specifically Ven-Aza, and Ven-HMA, both in the early settings in newly diagnosed patients as well as in the relapsed/refractory setting. So a very good setup for this new offering – potential offering in 2024. So let me tell you a little bit about the pivotal program. It's a very ambitious program. This drug went into patients and from first patient to NDA filing, it's less than 4 years. There aren't a lot of companies that can say that. It's actually about the same amount of time for our axatilimab program as well. So we've been able to execute very well. And I give that credit to the team for really carrying this program through. We started out with a Phase I, 125 patients or thereabouts were dosed to get to an RP2D that covers both KMT2A and NPM1 patients. We moved on and designed a very robust Phase II program in 3 separate cohorts, AUGMENT-101, 2A, 2B and 2C, all sized at 64 patients with a CR CRh endpoint. We had received breakthrough therapy designation from the FDA back after we had presented our Phase I data, which resulted in the ability to take the first 2 cohorts for KMT2A and pool them together and design an interim analysis, which we actually enrolled and then hit the interim analysis in the trial was stopped early for efficacy back in the fall. We actually top line that data in October. And under RTOR, which we received and the agency had invited us into that program. We're able to submit in real time the NDA. So that was what I had mentioned at the end of '23, we submitted the NDA. The NPN1 cohort is continuing to enroll against 64 patients, and we expect to enroll that at the end of the first quarter, beginning of the second quarter with data coming at the end of 2024. So a very ambitious program. We do expect to have our last milestone being a filing for NPM1 sometime in 2025. So this is the data that was presented at this year's ASH. This is our pivotal program for KMT2A. I'll just reprise some of the data points that are important here. But I think what comes to mind here is that we have a very compelling profile for a new drug to treat patients who don't have really any therapy that works for them. 63%, about 2/3 of the patients actually had cleared their tumor burden. So that is a very impactful number for physicians when they look at, okay, well, are my patients going to be impacted by a new drug for their cancer specifically and 63% of patients had a response. 23% had a CR/CRh, that's the regulatory endpoint, which met the mark and we ruled out a lower bound of 10%, so we were able to statistically have a statistically significant result. 70% of the patients were MRD negative. So at the most sensitive measure, we're able to eliminate the tumor and show that it is completely gone. Patients live for -- here, we've shown overall survival of about 8 months, which compares to about, as I mentioned earlier, 2.3 months in the third-line setting. So patients are doing very well [ enabled ] to stay on drug. We've seen responses across all the major subgroups. And more -- very importantly, the favorable safety and tolerability of this drug, very low discontinuation rate in the trial. So patients are able to really benefit and stay on therapy for quite some time. So really what physicians are looking for in this patient population. Again, I'm talking about relapsed/refractory KMT2A disease. They have been looking for a drug to treat these patients who, by the way, are on average 35 years old. So in our trial, that was the average age. These patients have a lot of living to do, but yet they have this terrible diagnosis. What physicians are looking for, they're looking for a drug that can get their patients to a complete response. As I mentioned, 63% -- 2/3 of the patients are getting to a complete response. They want to drive them to transplant, take them to transplant as quickly as possible, and they want to put them back on drug and maintain them in remission because they have a very high rate of relapse. You want to keep them in remission on drug for a long period of time. That is the paradigm for KMT2A. Physicians have never had that for these patients, but this is the drug to deliver for them. So we are extremely excited, physicians are excited about what's possible for this new medicine. So this is additional data in NPM1 patients. I mentioned KMT2A. This is the other -- this is the mutation that makes up 30% of AML. This is our Phase I data. We updated it in the fall of last year. And the reason that it's important is that it's highly consistent with what we're seeing for our KMT2A patients, a high rate of overall response, 50%, 36% CR/CRh rate, which would be the regulatory end point in a pivotal trial, very high MRD rates. So these patients are really getting to a deep durable response. We've seen patients in remission for more than 22 months, a couple of years. That is a long time. Again, these are patients who have been treated with prior therapies. They've had stem cell transplants. They have a very poor prognosis and yet we're extending their lives for quite some time. So this is really impactful data for this population, which we're following up with -- as you know, the pivotal trial, which we'll read out at the end of this year. So as I mentioned earlier, we also have combinations now we can say with some certainty that the ability to treat patients, newly diagnosed patients in the frontline setting, both NPM1 and KMT2A is possible for revumenib. The standard of care Ven/Aza, combined with revumenib, shown here in this Beat AML trial. This is a cooperative group trial, 13 patients, 100% response rate. All the patients responded. Almost all of them are MRD-negative. There's one patient who actually wasn't tested, so we can't say that they're MRD negative. But the high degree, we have a high degree of CR-CRh, which adds to what the standard of care Ven/Aza yields in their approval trial. Early days, of 13 patients, but I think we're super excited, and the investigators are excited that this is an agent that adds the standard of care from an efficacy standpoint. And importantly, from a safety and tolerability standpoint, doesn't introduce new toxicities. So very promising result. We also saw a combination also at ASH, a Ven-HMA combination. This is an all-oral regimen. [ Dr. Ghayas Issa ] MD Anderson has been running this trial, 9 patients. Again, patients who had received -- already had received most of them, venetoclax and stem cell transplants. And here, they are 100% response rate. So we're adding to this regimen and getting very good results. You're seeing no more toxicity than you're seeing from the doublet alone. So again, this gives us the breadth of opportunity to treat patients not only in relapsed refractory disease for using a monotherapy of revumenib, but also combining the way physicians may want to use the drug in the future for relapsed/refractory disease as well as in the frontline setting. So we'll have more data. Dr. Issa is following this trial up and doing an expansion here, and we'll have Beat AML, more data from that trial in 2024 as well. So we do have a pretty ambitious set of goals for revumenib and how do we take this to new settings. Right now, on the right side, you see relapsed/refractory disease. We have the monotherapy trials ongoing, and we'll have data for NPM1 in '24. We have AUGMENT-102, which is a chemo combo. Also, we presented data. We're not showing it here, but we presented data at the ASH meeting. And then the SAVE trial, which was likewise presented, I just reprised the data for you. So many regimens, several regimens in relapsed/refractory disease and then also going to the front line, and we have Beat AML in Phase I and expanding to Phase II. And also, we'll be starting trials in the frontline setting, revumenib plus intensive chemotherapy 7+3 -- moving on to maintenance. So multiple settings being able to address both NPM1 and KMT2A in the frontline newly diagnosed patients for what they call the unfit population where they use Ven/Aza, and the fit population where they use chemotherapy and then also using it in a variety of ways in relapsed/refractory. This is how you control the landscape. We will be the first, and we believe best menin inhibitor on the market. We'll have the drug on the market if it's approved, probably 2 -- at least 2 years in advance of the rest of the competition. So this is the market as we see it, the market opportunity, we think it approaches $4 billion to $5 billion in total in all the different segments. As you noticed on the lower left there, the relapsed/refractory KMT2A and NPM1 population it's about 5,000 to 7,000 patients and represents close to a $2 billion market opportunity. And that expands as you add the earlier line indications up to more than $4 billion. So I've talked a lot about revumenib. Let me move on to axatilimab and quickly go through that as well. So this is our CSF-1R antibody, which we obviously have done our pivotal program in chronic graft versus host disease, and we expect the drug to be approved in '24 with opportunities to expand. We do have a partner Incyte as our partner here, and we've been working closely with them to advance the program. There are about 14,000 patients who have chronic graft versus host disease. If you don't know, this is a complication that arises out of stem cell transplants. So patients receives stem cell transplant and get this multi-organ fibrotic and inflammatory disease and it's quite difficult to navigate. So it is a growing market, and that is something that we are obviously looking to impact. So what are physicians looking for? They're looking for a drug that has obviously a new mechanism. So we're bringing this chronic -- I'm sorry, CSF-1R antibody to affect the macrophage, which we think is a very important point of differentiation for this drug. It benefits both fibrotic and inflammatory components. And what we've seen in trials today, very consistent results across all subset of patients and all organ systems. And as I said, it's a multi-organ disease. So you have fibrosis across a number of different areas. The trial that we ran as a -- it's a known as AGAVE-201, -- it was a global trial, 241 patients randomized 1:1:1, 3 different doses. The endpoint in this trial was overall response rate by cycle 7, day 1. And the statistical significance was to exceed 30% as a lower bound. We did look at secondary endpoints, such as duration of response. And obviously, we hit the -- I don't think we show it all the detail here, but we did hit the endpoint for all 3 doses in this trial. So this is the focus on and what we presented at the plan area that focus on the 0.3-milligram per kilogram dose every 2 weeks. Responses were quite durable and really were accompanied by a reduction in symptom burden. And if you look at this as sort of best-in-class efficacy, 74% overall response rate by cycle 7, day 1, the primary end point, 60% of the responders were maintaining their response at 1 year and 55% of the patients and the self-reported outcome on the Lee symptom scale have reported more than 7 point decrease, which is highly significant. So not only did we reach the primary endpoint, but we showed durable responses and a reduction in symptom burden, which was noteworthy. And the drug is extremely well tolerated with adverse events consistent with on-target effects of CSF-1R inhibition. So this -- I mentioned the multi-organ disease. This is a breakdown by organ of how patients reported. So the complete response and partial response. I'll note a couple of things. Number one, in the lung, which we are going to do an IPF trial. We just started an IPF trial, which is very exciting as a next indication, but I'll note the lung in this indication, you generally don't see complete responses in lung and it was very noteworthy to physicians. I'll also note, in terms of skin, the 27% response rate, if you dig in 44% had a reduction in their BSA involved by sclerosis. Sclerosis of the skin is a serious complication and 66% had improvement in skin and joint tightening severity, which indicates that patients are actually benefiting significantly from this drug in very hard-to-treat organs such as the skin and from the lungs. So it's a big market opportunity, we believe, for in chronic graft versus host disease. I mentioned the 14,000 patients. About 5,000 of them are treated in the third-line setting. We are also looking to expand the use of this drug into earlier-line settings. The way to do that is you combine it with drugs like Jakafi and steroids to move it earlier in the treatment paradigm. And those trials are going to be initiated in the middle of 2024. And as I mentioned, we have the -- we'll have approval, we believe, in '24 as well. We'll be expanding -- Incyte will be expanding the use of this drug and developing it outside the U.S. where the patient population grows significantly. And then as I mentioned, we started an IPF trial, really interesting new mechanism offering for these patients addressing upwards of a couple of hundred thousand patients. It's a very different dynamic in those populations in that market. But we think this could be quite impactful in a reasonably short period of time for those patients as well. So that trial is initiated, and we're excited to follow that up. So this is our cash situation. I'll mention -- I did mention early on that we did an offering at the end of last year following the ASH set of data presentations. Cash at the end of the third quarter was $379.3 million. We added $258 million net through our offering as well as some of the proceeds off of our ATM in the fourth quarter. And so on a pro forma basis, as of third quarter, were about $650 million on the balance sheet. Research and development expense, $160 million to $165 million for the full year and total operating expenses, $225 million to $230 million, which includes noncash stock compensation. So some milestones I won't reprise all the milestones. Let me mention a few. Again, we will, for revumenib potentially have an approval in adult and pediatric relapsed/refractory KMT2A acute leukemia in 2024. We say mid-2024. This, again, is being submitted under RTOR, and we have constant interaction with the agency. So it's a really intense period for the company, but an exciting one. We will be starting some combination trials, both with intensive chemotherapy for patients who are known as fit in the frontline setting as well as following up on Beat AML and the unfit population in combination with Ven/Aza. And we'll be expanding some of the other trials that we're doing and we're starting a trial for Ven/Aza in the frontline for a pivotal trial by the end of this year. And for axatilimab, again, we hope to have the drug approved in the middle of 2024 for -- that's again for a third line chronic graft versus host disease, and we'll initiate combinations with our partner, Incyte for combination for Jakafi as well as for steroids in mid-'24. So a very exciting year for Syndax as we transition to a commercial stage organization. There aren't a lot of companies that have 2 products at our size, actually going to be -- hopefully be approved in the -- really at the same time. So it's a time of growth, and we're just quite grateful for all the work that's gone into these 2 programs, and we thank you for your support. So with that, maybe I'll stop for questions.

Thanks, Michael. [Operator Instructions] But I will kick it off with a question. I guess coming out of ASH, when you think about KMT2A and what you learned at the meeting, what are the read-throughs as you think about what you learned at ASH KMT2A that's applicable to NPM1?

Well, look, I think the -- and I mentioned it in my talk, I think the consistency, we had updated the NPM1 data back in the fall. So we know that the overall response rate at 50%, the CR/CRh rate is about 36%. And as you saw, the pivotal data displayed for KMT2A, our overall response rate in the 60%, 65% range and a CR/CRh rate of 23%. Very similar numbers and consistent with what we see for NPM1 in that data set. I think the other part of this is that we've been able to show patients who are dosed NPM1 and KMT2A in earlier line settings with Ven/Aza, as well as in the relapsed/refractory setting. And they're -- we're seeing pretty much identical type responses -- we're seeing patients stay on drug for a long period of time, go to transplant, go back on drug, stay on drug and be in remission for months, if not years. That applies to KMT2A and it applies to NPM1. So we see consistency across the board, and we just saw more data to demonstrate that at the ASH.

Questions from the audience.

At ASH, we got a lot of combination updates. And then today, in your presentation, you talked about starting some combination studies this quarter as well as Ven/Aza combo at the end of the year -- maybe just what is the broader sort of strategy for combinations for revumenib?

So the broader strategy is really focused on Ven/Aza in the frontline setting, for patients who are unfit. So that's about half the patients or so who are not fit for chemotherapy, right? So the standard of care is Ven combined with Aza, and we're making -- we're looking to make this a triplet. So can we add to that -- to that regimen to really impact these patients. That's one pillar of the strategy. Why? Because that's where all the patients -- or a lot of the patients are, not all of them, we have a fair amount of patients in relapsed/refractory disease, but you want to get these patients as early as possible and treat them for as long as possible, keep them in remission. And that's the place that you want to focus on time. But you can't do it without that combination regimen. Likewise, same thing goes for the unfit population, which is where patients who are -- sorry, the fit population, patients who are fit for intensive chemotherapy. You want to combine revumenib with intensive chemotherapy and impact their disease in a similar way, but drive them to hopefully a transplant, get them to remission, get through the transplant and then put them back on drug. Again, the earlier you can treat these patients, the better they do, the longer they stay on drug. And that is -- that's the paradigm. And you want to be able to access these 2 important pillars, it's 2 standards of care. There will be other combinations that we do, but they will be probably of lesser importance overall.

Questions from the audience? Yes.

[ When we ] expect on the launches this year, could you comment on commercial [ footprint on this ].

Yes. Question is with 2 launches coming in 2024, can I comment on our preparation – our preparedness. I'll say that we've been working at commercial -- the commercial preparation for quite some time. There are certain things you do within a short period of launch such as hire some sales reps and things like that. But we put our entire commercial leadership team in place, and we have a robust strategy to execute over the next handful of months until we're ready, and we will be launch ready in advance of any approval under any scenario. So this is a focus, I would call it a focused footprint for 2 drugs. So we have the co-promotion option, which we elected to do for axatilimab with Incyte. We just announced that. And that affords us about 30% of the FTE effort for axatilimab in the commercialization of that drug. And for revumenib, obviously, we're commercializing in the U.S. Our field force will be sized for revumenib and will accommodate our 30% for axatilimab. It's a very -- again, a very focused overlapping field force for -- to cover both drugs. And so that's a big advantage to have 2 products at the same time. So our preparation, again, starts with leadership, and then ultimately goes to our field force, which we will hire in 2024 in advance of launch. So everything is on track. That's a good question.

Additional questions from the audience? Go ahead.

You expect to launch in other countries – and your regulatory team is prepared to the [ launch of product ]?