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

All right. Good morning, everyone, and thanks for tuning in to our first fireside chat of the day at the B. Riley Oncology Conference Day 2. I'm Kalpit Patel, part of the biotech team here at B. Riley. I'm pleased to introduce our first fireside chat with Syndax Pharmaceuticals. We have the CEO, Michael Metzger; Anjali Ganguli, CBO; CFO, Keith Goldan, joining us from Syndax. If you have any questions for the team, please feel free to e-mail me at kpatel@brileyfin.com. With that, I'll pass the mic on to Michael. For those who are new to the story, Michael will give a quick overview, and we'll dive right into the questions then.

Great. Well, thank you, Kalpit, and thanks to the B. Riley team for inviting us today, and really appreciate the coverage and the opportunity to answer questions that anyone may have about Syndax. So let me just maybe start off by saying or positioning us as really in a unique way as a company. I think many of you know, both of our pipeline agents are in ongoing pivotal trials with data and potential regulatory filings in 2023. Both assets are poised to be first to market and potentially best-in-class targeted medicines within the hematology space, addressing what we believe to be multibillion-dollar market opportunities. Longer term, we're really excited that both programs offer the potential for very broad franchise opportunities beyond their initial registration indications. And recently, we did a financing in December of last year. We closed a financing, $172.5 million, which brings us to roughly $500 million on a pro forma basis. We'll be able to deliver based on that cash balance, be able to deliver significant clinical and regulatory milestones this year and potentially launch both of these products down the line as well as execute on selected business development transactions, which, as you know, feeds our early pipeline. So this is, I think, shaping up to be a really, really important year for the company, an exciting year for the company of growth with several key milestones, of course, which we'll talk about. And we'll talk about our 2 individual programs, which really address major unmet medical need within the hematology space. So excited to dive right into it. So thank you.

Thanks, Michael. And a lot of the conversation lately has been focused on revumenib, right? It's been an important -- you've had an important update recently. But I want to maybe do this differently and start with your second asset first, axatilimab for chronic graft-versus-host disease. You have a pivotal trial that's ongoing. Talk to us about the data that you've seen in chronic graft-versus-host disease. You've had an 82% response rate at month 6 and a 50% response rate -- sorry, 50% response rate at month 6 and 82% by month 6. So how competitive is this profile in your view and in the landscape of cGVHD agents?

Yes. Thanks, Kalpit. So I think this is -- just to start off, I think it's a very competitive profile, and it's an emerging commercial space and opportunity for new medicines to treat chronic graft versus host disease. The data that you quoted was from our Phase II portion of the trial that we presented at, not this past year's ASH, but the ASH before. It was recently published in Journal of Clinical Oncology. This is data that was in 23 patients, 1 milligram per kilogram of axatilimab given every 2 weeks. And that's one of the doses that we're testing in our pivotal trial. And as you laid out, 82% of the patients responded to treatment within the first 6 months and 50% were in response at cycle 7, day 1. So yes, this is -- I think based on the approved agents, recently approved agents, this is what we believe to be a very competitive profile. And if you look at Jakafi and belumosudil, they had data in the 70% response range -- 70% to 80% response rate in the first 6 months and 50% for Jakafi at cycle 7, day 1. So again, very similar. Importantly, this is data that we accumulated in our trial after 3 prior treatments. So these are very heavily pretreated patients in the relapsed/refractory setting, perhaps another line later than some of these other agents that were approved. And I just quoted some of their data. So we are seeing excellent cross-organ responses in chronic graft-versus-host disease. And what I mean by that is it's a multi-organ manifestation of disease, and what physicians are looking for is having responses in areas such as lung and skin, and then you get them in multiple organs. And so those are 2 of the more difficult-to-treat organs, and we've seen really very good responses in those areas. And I'll also note that we've shown in our early trials that we've been able to reduce the use of steroids for these patients, which, of course, physicians are keen to do based on the long-term effects of steroid treatment. So all in all, I think a very competitive profile to what agents have been recently approved, but we're certainly going to test that further in our pivotal trial.

Okay. And what about the durability in the Phase II? Can you comment on the median duration of response in a 1-year -- maybe a 1-year response, if you have that data?

Yes. So you may not know, but the median duration of response in the Phase II was not reached. So that's an ongoing question, right? But the majority of patients in that trial have been offered greater than 6 months. And there were, I think, 6 patients out of the 23 that were on over 1 year. So I think the overall durability will be, again, tested in the pivotal trials, but I think it's a very good sign that patients are not only tolerating treatment and getting responses but staying on for a very good amount of time.

Okay. And if I recall correctly, the baseline demographic [ PAD ] patients who received other newer drugs like Kadmon's drug, ibrutinib or even ruxolitinib, do we have response data in patients who had prior exposure to these agents?

Yes. I think we have seen that in our trial. I think it's relatively small numbers of patients who have been through these other treatments. But I think -- and again, the overall Phase I, Phase II was a small number of patients. But I would emphasize that we have seen patients come on our trial who have first received Jakafi and/or belumosudil and have done well. And I think that's due to the fact that -- and this will bear out in the pivotal trial due to the fact that this is a different mechanism of action. So this is directed at the monocyte-macrophage lineage. The other treatments are more B-cell, T-cell directed. And so the fact that patients respond to a different mechanism of action is not a big surprise to us. Certainly, we'll see more patients in the pivotal trials that have gone on these other agents and then come on our trial.

Okay. And maybe some color on the side effects that we have seen in the Phase II. I'm noting lower rates of ASP, ALT increases, significantly lower rates of CPK increases and lower lipase increases in the Phase II versus the Phase I. I guess is that just a function of patients in the Phase I maybe receiving higher doses when you're dose escalating and you didn't see that as you sort of moved on into the Phase II?

Yes. Maybe I'll ask Anjali to address that, please.

Yes. Thanks, Michael. And yes, Kalpit, thanks for the question. I think it's actually kind of hard to say because most of those higher increases did come from the increased dosing, which was in a very small number of patients. So we've included both the 1 mg per kg every 2 weeks and the 3 mg per kg dose every 4 weeks in our pivotal trial to really test the hypothesis to see if there really is a difference in the therapeutic index between those doses. A lot of those, if not all of the AEs that you cited, are on target AEs for inhibiting the CSF-1R pathway. Basically, as Michael mentioned, you're shutting down the macrophage. And in the liver specifically, the Kupffer cells are the macrophage population that clear a lot of those enzymes. And so you're basically just inhibiting clearance. It's not actually a signal that there's liver damage or toxicity building up in the liver. And what we see based on our dosing schedule is there is a period of time before the next dose where the macrophages recover and clear those enzymes. And so just naturally, those levels go back to normal before the next dose. So there's no accumulation of this effect either. So we'll see in a larger population and longer treatment how that really plays out and if there's a true difference between those doses.

Okay. Okay. That's helpful. And the discontinuation rate related to adverse events was, I believe, between 8% and 9%. Based on the design of the Phase III, would you expect similar discontinuation rate? And how does that maybe fare relative to approved agents in this setting at the same follow time -- median follow-up time?

Yes. Anjali, do you want to take that one as well?

Yes, sure. I think, Kalpit, in this pretty heavily pretreated population, I think an 8% or 9% discontinuation rate is very acceptable. The Phase III is actually designed very similar to the Phase II expansion. And so it could be that we get a few patients that are earlier lines and maybe more fit, if you will, to tolerate any type of therapy. But overall, we've seen a very tolerable profile with axatilimab. And as Michael said, we've had many patients -- a good portion of patients stay on for over a year, even some over 2 years. And so we're not too worried about toxicity. I think the bigger question is what will the patients respond to, how severe is their disease, and that is usually what is leading to discontinuation.

Okay. And one item that I've heard from investors is that despite showing promising efficacy in chronic graft-versus-host disease, they're sort of wondering how the non-oral formulation sort of weighs in here, right? I mean I think Kadmon's drug was an oral drug, and the feasibility of something oral is much easier than an IV administered drug. So is that really a hurdle based on the disease management and how often patients are seen at the doctor's office and perhaps for product life management purposes?

Yes, Kalpit. I think we don't see it as a barrier. In fact, our research seems to suggest that physicians like to see their patients in this setting pretty regularly. These are, I would say, pretty sick patients and high-touch patients. And so the idea here is that while this is an IV regimen, all these patients will cycle through treatments, right? They have limited options. And so it's a very severe disease. And so the physicians are looking for tolerability. And they're also looking, first and foremost, for efficacy. And I think as long as our agent can deliver on those 2 pillars, I think we're going to be in a very competitive position. And I think the fact that they're going to see their patients relatively often -- and as you know, we're testing every 2 weeks -- every 4-week dose in the Phase III, which may be a little bit more convenient over the long term. But we haven't received any pushback from physicians that this is not a convenient regimen for patients to take. And in fact, as you know, they're staying on, in some cases, for a long time. So that's -- I think that pattern bodes well for the future of this drug. And also, I would say that life cycle is something that we think about with our partner relative to things like subcu and other regimens. So I think that's something that's on the table for the future. We haven't talked much about our plans for that, but there's certainly, I'd say, the open possibility that that's something we pursue in the future as well.

Okay. Sounds good. Let's maybe switch gears to revumenib. This is a Menin inhibitor that's being advanced for advanced leukemias. You've shown an impressive 27% CR/CRh rate at the RP2D in both KMT2A rearranged patients as well as NPM1 mutated patients. Talk to us about the patient groups that were treated in this trial as well as the efficacy expectations with salvage treatment in this setting for both ALL and AML patients?

Yes. So -- good question. So let me talk a little bit about the population first. So this is a heavily pretreated population, median 4 lines of -- prior lines of therapy. In the trial, 46% of the patients had at least one prior stem cell transplant, 60% had prior venetoclax. And I'd say a significant percentage of patients had co-mutation. So these are complicated patients and very late-line patients. The alternative for these patients versus getting a therapy that addresses their mutations such as revumenib really is hospice, right? I mean they're not able to tolerate any additional treatments. They have exhausted chemotherapy. They've exhausted targeted therapy. So they're really at the unfortunate end of their patient journey. The results we showed here, median overall survival is something that stands out to us of 7 months. We know third line or later -- third-line patients in this setting overall survival is less than 3 months. So again, this is an early trial, but very promising result on survival. At the recommended Phase II dose, the CR/CRh rate was the same in both MLLr and NPM1 subsets, which I think you quoted is 27%. We thought there was a pretty impressive median duration of response of 9.1 months at the data cutoff. And the median time to response is important. So patients don't have, with this disease, a lot of time to wait for a response. And the time to response median was 1.9 months, so very quickly. And I think the important thing to again remind ourselves here is that these are patients that have gone through 4 prior lines. So they're essentially fifth-line patients. And what that, I think, speaks to in particular is with good results like this, how would you do in earlier-line settings. And certainly, in combination, you'll do that in combination in earlier line setting. So establishing ourselves with single-agent activity -- strong single-agent activity for NPM1 as well as KMT2A is, I think, a really good start to not only get the drug approved but essentially see potential utilization in earlier line settings, which we'll do more work on.