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

First and foremost, for all those in the audience and listening on the webcam on the presentation. It's a pleasure to have everyone back in person, management, investors, et cetera. So it's fantastic to having your support and enthusiasm for this event after 2 years, we're kind of coming back to norm, and my name is Peter Lawson. I'm 1 of the biotech analysts. I'll be hosting this fireside chat with Syndax. And I just want to thank Michael Metzger, CEO from Syndax. And I guess the first thing, I think, Michael, you can just talk through the kind of corporate overview, maybe of how you differentiate within the space and how the year has been for Syndax.

Yes. Well, first of all, thank you, Peter. Thanks to Barclays for inviting us to speak today, and it's nice to be back in person finally after 2 years of doing Zoom meetings. But let me first start off. Do we have the slides? Corporate didn't...

Are you okay?

Yes, yes. So in turn, I'll just start even if the slides aren't advancing yet. Well, I can say it's been a transformational year for Syndax, 2021 that is, in the sense that we now have 2 pivotal programs going after 2 areas of high unmet medical need. The first being in acute leukemia and the latter being in graft-versus-host disease, chronic graft-versus-host disease. But now we're in pivotal trials. We've done 2 pivotal trials, and we're extremely excited to be in that position as a company. We had data presented last year at ASH, oral presentations on both programs, really highlighting the differentiated nature of both of these programs, very well received. We did a -- what we thought was an incredibly important partnership with Incyte at the end of the last year. Incyte for our axatilimab program, it's a global collaboration, really set the company up for real expansion with that program. So we feel like we're in a very good position to maximize the opportunity there for axatilimab. And lastly, we did a follow-on financing, $86.5 million, brought in some new investors, long-only funds that we were keen to have in the story. And so we find ourselves at the end of 2021 and now starting '22 with a full balance sheet, roughly $440 million of cash on the balance sheet, a great partner, 2 programs in pivotal trials and really well set up to take advantage of what we think is a very important pipeline for Syndax. So that's at least where we start the year. And now that the slides are back...

Now the slides are back.

It's just a snapshot. The next slide is just a snapshot of our corporate pipeline and sort of what our priorities are as we look at the next year. On the left, we talk a little bit about our Menin program 5613, which is a first-in-class, best-in-class inhibitor. We were the first ones to show proof of concept with this molecule in this set of indications, going after both NPM1 acute leukemia and MLLr-rearranged leukemia. We -- as I mentioned before, we have 2 pivotal -- we have a pivotal program ongoing. We're enrolling patients quite well. It has 3 individual cohorts of patients spanning both AML and ALL. And we're really excited that this year, we'll have at least 1, if not 2 of the cohorts fully enrolled, and that will lead to top line data sometime in the first half of '23 and the potential filing in 2023 for that molecule. We're also initiating combination trials, getting into frontline maintenance and so forth. And so it's a very broad program, one where we have first mover advantage. We believe we'll be first-in-class and ultimately best-in-class there, and we feel like we're set up to push our advantage and really build out that program. And then in terms of axatilimab, I mentioned our partnership with Incyte, which really allows us to expand there. In addition, we have our pivotal program ongoing. AGAVE-201 is our pivotal trial. That's enrolling patients quite well. It's a global trial. And we'll be initiating, through our collaboration with Incyte we'll be initiating other combination trials with their JAK portfolio in the frontline setting, as well as what we're doing in the relapsed/refractory setting with the AGAVE trial. So that's a very broad chronic graft versus host disease set of studies, and we're now initiating in the second half of the year an IPF trial, where we think the mechanism of action could be quite impactful. Obviously, a very large indication and one that we could drive a lot of value by having a positive outcome there. So really a pipeline full of build-out and opportunity for us, and we think we'll be building a lot of value this year. And in addition, our business model is to in-license or acquire assets, oncology assets that is. And we feel like this is an opportune time to be looking to do that and bring additional assets into the pipeline in 2022, and we think the balance sheet really supports that as well. So a nice setup for us going into '22 and plenty of interesting work to keep us busy. [ So it's going to ] ...

That's great. And just maybe leveraging off that last point about opportune time from looking for assets. In stark contrast, it sounds, to pharma companies saying that assets are still expensive or price points are still expensive. How do you kind of judge that? What's your kind of ...

Yes. Well, we're certainly not a pharmaceutical company in the sense of Big Pharma, but we do hunt and look and talk to lots of companies, big and small, about their assets and potentially acquiring them and bringing them into the pipeline. I think it's a fertile time to have the conversation. I think last year perhaps valuations of companies were high, [ but ] obviously when they were a lot higher assets were able to be funded throughout the pipeline. Many companies had cash. And I think this year, it's a little bit different. And so companies are willing to have conversations perhaps that they weren't willing to have last year. And certainly, that seems to be the case for us. We'll have the opportunity to bring in additional assets, we believe.

Do you think there should be industry consolidation?

[ You know ] a lot of companies. I mean, you probably cover 50 companies. So I feel for the analysts. But there are -- look, I think there's a lot of capital being deployed. There has been a lot of capital being deployed. There are probably not as many assets to develop, and there are a lot of teams that perhaps don't have as much experience. And that's a hard place to be in a very difficult business, where you have to develop assets, and drug development expertise is just not the same everywhere. So I could see consolidation being a reality over the next year or 2 years as capital starts to dry up in certain cases. And look, I think there's an opportunity for companies like ours that have what I think is great expertise and a track record really for developing great molecules. I think companies like Syndax have -- really offer companies something in terms of taking their assets to the next stage.

Yes. It's a clear point of differentiation. I'd love to talk about the menin inhibitors of data -- updated Phase I data this year. What should we expect to see in terms of NPM1, MLLr, durability, that kind of thing?

Yes, I think our focus, we have presented Phase I data at ASH, as I mentioned earlier, in 2021. That was the full Phase I data set, 59 patients, 51 of which were either MLLr or NPM1. That data set showed not only full safety but efficacy, and first look at durability. And the median durability was not reached in that population of patients. And so as of today, we feel like these are -- this is a good indicator of perhaps long durability for this patient population in the relapsed/refractory setting relative to other agents that have been approved. And so this year, we're very much focused on our pivotal program in getting those cohorts enrolled. We don't have -- we haven't provided guidance that we're going to be updating the Phase I data set. We're really much more focused on getting the Phase II enrolled. As I mentioned, 2 -- probably 1 or 2 of those cohorts will fully enroll this year, and we'll have top line data in the first half of 2023.

Okay. But Phase 1 surely, that would be a good update at something like ASH?

It could be. I think we're not guiding that we will have data at ASH. It's certainly possible that we could take another look at the durability, for instance, on the Phase I. And perhaps that's a 6- or 12-month update from the last data cut, which would put us sometime in the end of the year. But again, we're not speculating that we're going to absolutely do that, there's a possibility. But more likely than not, we will not do anything with the data set in terms of efficacy or safety. That was a full data set at the ASH conferences.

Got you. Okay. And then I guess, how much data do you think we would get then from the Phase II like first half of '23, I guess, we see the initial cut.

Right. So a reminder, these are 3 individual cohorts, they enroll separately. So 2 AML cohorts, 1 NPM1, 1 MLLr and an ALL cohort of MLLr patients as well. All of them are 64 patients. So it's -- the powering is off the set of 64 patients. An additional 10 pediatric patients can be enrolled in each of those cohorts. So that's the totality of the data that you would see in any 1 of the cohorts that enroll. So it's just, we don't know if we -- at this point, whether we'll have 1 or 2 or even 3 enrolled by that time. So we're sort of waiting on the kinetics of enrollment to tell you exactly how much patient data will arrive in the first half of '23.

Got you. How quickly would you launch or prepare to launch?

Yes. I mean it depends on -- people will tell you, you need to launch -- you need to put your commercial organization together rather early in order to leverage an opportunity. I think we have already started our pre-commercialization work, and we'll be hiring the leadership for commercialization in the latter part of this year. So we are well underway with commercial planning and building out the -- starting to build out the organization to support commercialization.

Okay. So we should kind of see expenses around year-end...

Yes. I mean I think the expense guidance for the year is $160 million to $170 million. That includes whatever commercialization work we will be starting in 2022.

Okay. That's perfect. And then the AUGMENT-101 trial with strong versus weak CYP3A4 inhibitor, you've kind of prioritized the strong. What's happening with the weak? How do you kind of backfill that or back out the right response?

Yes. So I think the idea of prioritizing the -- and putting all the patients that are on -- right now that are enrolling in the Phase II cohorts on a strong CYP3A4 inhibitor. The reality is that the vast majority of patients are on azoles, and the majority of those are on strong CYP3A4 inhibitors. We have that dose going in all 3 cohorts. Really what we're trying to -- what we ultimately need to understand, in addition to what the safety and efficacy is of our 163 BID dose, is to sort of match up the PK of a dose adjustment for patients who are not on a strong CYP3A4 inhibitor. And that data will be collected in the course of the phase, in the Phase I that we have ongoing in the background. So a certain number of patients, we want to enroll them as quickly as possible in each of the cohorts, the clinpharm -- what we term a clinpharm question about those patients who are not on a strong CYP3A4 inhibitor, how do they -- what does their PK look like? What would their dose adjustment, therefore, need to be? That question will be answered once we've enrolled at least 1 of the cohorts. At 163, we'll open up some space in the Phase I, and we'll backfill and understand that question.

Got you. Okay. And as we think about the competitive landscape, how important would that gap between you and the next player is, I guess, Kura. How important is that, do you think, for commercialization?

Yes. Well, I think being first to market has actually been proven to be very important. I think you want to be first and best, and I think we have every reason to believe that, that's where we'll be. But it does set up the opportunity for physicians to use your drug, get comfortable with your drug. And ultimately, that leads to additional trials, and we expect to be very active, as I mentioned, in other settings as well. And so it's very important to kind of build your franchise as quickly as you can and build mind share with physicians as they get a chance to utilize the drug and see how it performs in patients. So we believe it's important.

Good. How far ahead do you think you are from Kura?

It's a hard question to answer at this point. We believe we're pretty meaningfully ahead, and I'm not going to hazard a guess exactly how far, but we think -- we know we'll be first to market.

Would you measure it by like the recommended Phase II dose? Is that a sensible kind of measure of how far ahead? Or is it the start of a pivotal trial? What's the most sensible metric in your mind?

Ultimately, whoever gets approved first will be that much far ahead. I mean it's almost impossible for me to give you a precise answer to that here.

Okay. I'll put that in 2 years. Okay. That's good. Yes. Kura [ senses ] to 12 months. So I don't know if that's something you want to comment around.

I don't want to comment on that.

Okay. I fully understand. And I guess the next step on that is, of course, a first line trial, which what you're doing through essentially an IST right...

Not an IST, but so there are 3 trials that we're -- I think I mentioned earlier that we're starting this year, actually this quarter and next quarter. One is a frontline trial in combination with venetoclax and azacytidine. That will be our first frontline trial in combination. We're also doing a chemo combination trial, which is in relapsed refractory, but that will, we think, inform how patients do in combination with chemotherapy. As you know, there's the fit and unfit population of patients. In the fit population they take 7+3, one of the chemo regimens. So this is sort of a first look at chemo combinations, which we think is rather important. And a third trial we're doing with Intercept, which is another master protocol. I mentioned the first trial in combination with [ ven aza ]. That's what we call the BEAT AML trial, it's part of LLS, one of the cooperative groups that's active in this -- very active and important in this space. There's an Australian group that leads the INTERCEPT trial. They're -- also have a master trial. They're looking at patients who have actually achieved remission but have MRD-positive disease. And we'll be looking to see if we can make an impact and turn that into MRD-negative disease. It's an important, very important area of investigation, we believe.

How does the relapsed/refractory chemo inform about first line? Does it kind of help you understand the right dosing, or...

[ Well that's ] -- you can get a sense about dosing, whether these mechanisms are -- are they added -- are we adding anything to chemo? Are they tolerated, well tolerated? Those are important questions to answer.

Got you. And then the frontline trial, would that be -- is that pivotal? Could you file with that?

Which trial?

The venetoclax.

The venetoclax, ultimately could lead to approval. I mean, it's versus the Phase I trial. So we're going to look at safety. We'll get a sense of efficacy. And ultimately, over time, yes, the idea is that it could essentially end up in registration.

Got you. And then I guess the Beat trial is kind of intriguing. So you get the patients into remission, transplant and then you can then continue on therapy. So it's almost like a maintenance [ setting ].

Right. So there is the opportunity to do that as well. And maintenance is an important indication, really hasn't borne out for most agents in this space. It's a nice dream to have in the sense that you can intervene with patients early, get them on treatment, whether it's combination or monotherapy, hopefully get them to bone marrow transplant and then put them back on drug after they've engrafted. I think that idea, whether it's coming through the frontline setting or in the relapsed/refractory setting, both of those ideas and maintenance lead to longer time on drug and potentially a much bigger opportunity for 5613.

Got you. And then for the chemo relapsed/refractories of AUGMENT-102, kind of what do you want to see at that point? What does -- how much does chemo add in the sense of get the response or durability? How should we be thinking about the benefit and what's the bar?

Yes. Well, we're going to find out, right? In this setting, actually chemo doesn't perform particularly well. These are patients who have had usually multiple chemo regimens at this point. And so putting them back on chemotherapy at that -- in the relapsed/refractory setting often is not a great set of outcomes for these patients. They just -- there's just unfortunately, nothing else that they can take. And so adding a targeted agent and seeing sort of a response rate roughly what we saw in our Phase I trial, call it in the 20% to 30% range, that would probably be a very meaningful response for these patients.

Got you. Okay. So because you kind of assume that they would normally have less than 5% kind of response rate?

Right. These patients are unfortunately not set up to do well at that stage.

Got you. And then I guess there's a number of additional endpoints that we start to see in AML trials, MRD negativity. Is that something that you'd be thinking about for the first-line trial or other lines of trials?

Right. So I think you know that the -- in terms of relapsed/refractory, there's -- in palliative care, it's -- CR/CRh is the regulatory endpoint. And then in terms of other settings, it's overall survival, right? Those are the regulatory precedents. In terms of MRD, drug has been approved on MRD negativity, but it seems to be a very important prognostic indicator. Another company has put forth a trial MRD negativity, looking at MRD negativity as a marker for survival. And so it's an important area of investigation, but MRD as of today is not itself a part of the regulatory framework.

That's something you wouldn't include or you would?

We will look at it. We'll look at it and it will be an important part of the package, we believe, and we think it's a differentiator for our drug. The high rates of MRD negativity is, as far as we know, haven't really been seen with other targeted agents to the extent that we showed it in our Phase I trial. And so to the extent we can continue to build on that, I think it does set up well for patient outcomes. So we'll continue to collect that, look at that.

And then just pediatric data you've shown has been really encouraging. And when do we see kind of an update of that?

On the pediatric data?

On the pediatric side.

Right. I think the only data that we've shown is sort of at the pediatric ODAC, and we showed some early data last year. There was a few patients [ of it ] in our compassionate use program, which we've had an active compassionate use program from the beginning of the trial [Technical Difficulty] [ of it ] in Phase I. We haven't really talked about updating that or publicly presenting any of that data at this point. I think the next look at pediatric data could be in the form of the Phase II, assuming that we enroll pediatric patients in any of the 3 Phase II cohorts.

Do you think there's going to be a difference in durability between MLLr and NPM1 patients?

Yes, it's a good question. I think preclinically, we'd say no. Based on what we've seen and based on the efficacy that we've seen so far in the Phase I, I think we would say we see deep durable responses, both MLLr and NPM1. So there's no reason to believe that they would be any different. So...

Got you. The -- I know Kura was talking about the MLLr and NPM1 patients in the relapsed/refractory setting that's seen a kind of an equal distribution, which is atypical versus what you would expect from the disease.

It's [ seen ] the same.

Yes, exactly. Did you see a similar kind of scenario as well, that maybe the NPM1 patients are being treated with other inhibitors and so that, therefore, they are not coming on to the trial?

Well, I think we have seen in our Phase I, what was apparent in our Phase I is that there were more MLLr patients than NPM1 patients. And I think we explained that part of that -- the reason for that is we were the first one to show activity in MLLr. And I think it engendered a lot of interest in the program from physicians who had MLLr patients and wanted to get them on our trial. And with limited slots on the Phase I, you're kind of put in a position where you can't get everybody on the trial, right? So we filled more slots of MLLr. And then over time, we had NPM1 patients come on as well. But I think it was sort of the kinetics of our trial and how that went. But there are also in the frontline setting, patients certainly in the unfit population get ven-aza, for instance. That also -- patients can do rather well with NPM1 in the earlier settings. But once they relapse, they tend to look a lot like MLLr patients in terms of their prognosis. So we think that this will ultimately even out as we get into the Phase II. There are obviously 3 separate cohorts. So we'll enroll 64 patients that are NPM1, as we will MLLr in each of the other 2 cohorts.

Got you. I've -- we've [ interact some ] extra time. So thank you so much. I guess we'll catch up on axatilimab another day.

Yes, terrific. Thank you so much.

Thanks for [ coming up ].