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

Good morning, everyone. My name is Jason Zemansky. I'm one of the SMID cap analysts here at BofA. Thank you so much for joining us on this, our last day of our 2024 Health Care Conference in Las Vegas. This morning, I'm pleased to introduce Syndax. With me today are Keith Goldan, CFO; and Anjali Ganguli, CBO. Welcome.

Thank you.

Well, let's dive right in. 2024 is set to be a transformational year for Syndax with 2 potential approvals on deck especially for investors who are newer to the story, could you provide a brief description of revumenib and axatilimab? And what should investors be focused on for each approval?

Sure. Thanks for the question. First, I want to start off by saying thanks to BofA and Jason and Cameron for having us here today. Yes. It is certainly a unique year for Syndax. Maybe I'll take a step back and just for those maybe a little newer to the story, give a little overview. We're a SMID cap biopharma company. We have 2 products, and I'm going to go in a moment, describe why I think we're really a unique story. I mentioned we have 2 products pending FDA approval in the third quarter of this year. We have a PDUFA date first on August 28 for a CSF-1R antibody called axatilimab. Last year, we completed a pivotal trial in chronic graft versus host disease. That product is partnered with Incyte, a leader in this GVHD space. And we were granted priority review. I'm looking forward to a launch later this year. Secondly, we have revumenib, our menin inhibitor. That is in registration right now for KMT2Ar acute leukemia with a PDUFA date coming up on September 26. So really uniquely positioned, I don't know of -- we don't know of any companies our size with 2 products in registration that will launch almost virtually right on top of each other. We're -- we have offices in Boston and New York. We're about 250 people.

Excellent. I mean, as you mentioned, these approvals mark the evolution of Syndax into a commercial entity. So maybe can you discuss some of the high-level work you're doing to build out the commercial infrastructure. Fundamentally, what do you think needs to happen from a broad level to ensure successful launches?

Yes. Maybe I'll take that, and you can add on, Anjali. So we -- I'll talk about the launches, but maybe also mention that the approvals that we're waiting for this year, just the beginning, we think, of the opportunities for both these products I mentioned start out with revumenib. That is, I mentioned in registration for KMT2Ar acute leukemia. Uniquely, we believe that this will be the first product, if approved, that is leukemia agnostic. We would expect a label that covered KMT2Ar ALL and AML in both peds and adults. We also have in registration with the agency, both at tablet formulation and a liquid formulation for pediatrics as well as for those that have difficulty swallowing. So another kind of unique characterization of revumenib in the inhibition field. We are building a commercial infrastructure to be able to launch the product in the third quarter of this year. What I didn't mention, pardon me, was that revumenib also under priority review, but it's being reviewed under the FDA's RTOR program. So the real-time oncology review. If you look at the precedent RTOR products that have been approved, SNDs and NDAs, typically, they are approved before the PDUFA date. So I mentioned the PDUFA date that we have is September 26. We are -- I wouldn't say expecting an early approval, but hopeful for an early approval. And we're committed to getting revumenib into the hands of patients and physicians as early as possible, as soon as possible when the product is approved. So the commercial infrastructure that we're building will be ready to launch in the third quarter, whether that a potential approval comes in July or August. We have the commercial leadership team in place. We have had market access on board for quite some time, developing relationships with payers. We have medical affairs team that's been deployed, building relationships with the KOLs who will be the early prescribers in the academic institutions for revumenib. But not only that, they're the ones that often are the ones deciding the guidelines, the NCCN guidelines. So we will be ready for a Q3 launch. With respect to axatilimab, I mentioned that we are partnered with Incyte on that program. They are the leader with Jakafi, which is approved for second-line treatment in chronic graft versus host disease, generally corticosteroids are the first-line treatment. We are going to be putting forward 30% of the commercial effort in that 50-50 U.S. commercial partnership. Did I miss anything?

For revumenib, I have to imagine that there's already a considerable advantage here, given that, as you mentioned, this is a new class. It's novel. There's a lot of buzz following your presentations at ASH in December. How do you leverage that in terms of medical access at this stage? I mean what sort of questions are you getting, particularly as you already have a significant extended access program with a lot of patients on therapy?

Yes. Maybe I'll start there. I think it is a really exciting time for this class of compounds and for physicians and patients because to date, there's really been nothing that works in the KMT2A rearrangements. And unfortunately, once patients get to the relapsed/refractory setting, their median overall survival is less than 3 months. And so now we have an agent where it's an oral, very well tolerated. It's getting more than 60% of patients into complete responses and enabling physicians to treat aggressively get these patients to transplant, which is currently the only curative pathway for these patients? And then they've been aggressively pushing us to enable them to put patients back on therapy post transplant because of the aggressiveness of the disease they want to give them the best opportunity to stay in remission and hopefully successfully cross the hurdle of tumor coming back. And so the goal here is to get patients -- for all physicians, the guidelines have pushed physicians who identify KMT2A rearrangements from the beginning, even though there was never specific therapy for them. But because you know it's so aggressive, they would push physicians to treat as intensely as possible and get those patients to transplant. That was the goal. So identification of patients has been there for a number of years, reimbursement for those diagnostics have been there for a number of years. And by the time they're relapsed refractory, you know who those patients are. So we don't have to change that aspect of the treatment paradigm. But now we're giving them a tool that actually allows them to get those patients to translate and do what they want to do. So that's been super exciting for the class. And I think it's helped build the excitement around what else can menin inhibitors do because they've seen how manageable the treatment is. And last year at ASH, you mentioned our data sets that we presented. I think we've put together such a fulsome series of information both in KMT2Ar, but also NPM1 mutations, which is another area of AML that's not -- that does not have a targeted therapy available. And we showed really strong, very consistent data in that population as well. We also had 3 different combination trials that we read out both in frontline and in relapsed/refractory with venetoclax combos and chemo combos, which further emphasized how much more effective those treatments can be for KMT2Ar and NPM1 patients by adding revumenib to that bolus -- or sorry, to that -- to those regimens. And I think that further enhanced the reason to believe, right? You're not -- it's not just working by chance in monotherapy, but you're seeing no matter where you give this drug, it's giving you more efficacy and the most important thing also as it was not adding any toxicity. If anything, a couple of the physicians said to us, well, perhaps it's actually improving the tolerability profile for patients because it's allowing the disease to regress so much faster. And a lot of the side effects that these patients suffer from is also because of the disease. So a lot of the cytopenias that you see are because of the leukemic process, not allowing your cells to develop into true blood cells. So it's been an amazing situation for us. And the very next hurdle with the approval, as Keith mentioned, in the third quarter, will be followed very quickly with top line data for the second population of NPM1 patients in the fourth quarter. And so right on the heels of the approval, we are very confident we'll have a strong data set suggesting the impact of menin inhibitors and NPM1 that can also lead to -- those patients do respond to intensive chemo, they do respond to ven/aza. But once those drugs stop working there's nothing else for them. And so again, another well-tolerated agent that could be added on the ven or given as monotherapy is a welcome addition for NPM1 patients. And further, we'll have -- we've -- as we mentioned last year, we've continued to build the data set for these combinations, and we'll have more of that data over the course of 2024 as well. So we'll have another very robust data set that pulls together right after we get approval and the only menin inhibitor available to actually utilize for any of these patients. So I think we've got a really exciting 12 months ahead of us.

Yes, absolutely. And I'd love to definitely delve into the overall potential of the menin class, but maybe one more quick one on the commercial outlook, at least near term. Cameron from my team had a few questions here.

Yes. So you've guided to an addressable market of around $750 million in the KMT2A rearranged relapsed/refractory setting. I'm just curious if you could maybe touch on what some of your assumptions are here. And realistically, how quickly you could get there?

Yes. So the $750 million was for all -- if you treated all patients with KMT2Ar. And the goal would be to try to get there. I think even TAGRISSO, which has 90% of the market is not at 100%. So there's always I'm not saying that we're going to get $750 million in revenue to Syndax. But that is the potential, as we know the data set and the landscape right now, what we think could be achievable. The way we get there is just looking at the data that we've presented last year in our top -- the data from our pivotal study in KMT2A, which showed 2/3 of patients responding to treatment. We also know that, that data set was collected in a pretty late-line population. So it was patients with a median of 3 prior therapies of fourth-line patients on average. And when we speak to physicians today, we're hearing that this is their treatment of choice in the second-line after a patient that's been treated with 7+3 and either is primary refractory, meaning they had no response to intensive chemo or they respond and relapse they're going to reach for revumenib. And so that's a much earlier line patient. They're probably not going to see or have had as many transplants as they had in our data set. And there going to be fitter and as you've seen with across oncology, the earlier you treat patients, the better they do and the longer they respond. So I think there's a lot of upside to these numbers. But if you're looking at fourth line patients, we saw 2/3 respond and 1/3 did not respond. The third that didn't respond on average were on treatment for 3 cycles. Of the 2/3 that responded, approximately half went on to receive a stem cell transplant. And then the goal would be to get them back on therapy after transplant. And that's what as I said before, physicians were demanding that we include that in our pivotal trial, we were able to do that. And we did see 50% of patients come back on in additional patients with the opportunity to elect to come back on at the time of data cutoff. But there's -- the sort of risk benefit there is very much in favor of let's just give them more drug and because otherwise, we know this disease is coming back. So in that population, we're estimating a median of 18 months of treatment for those patients, inclusive of pre-transplant and post-transplant. And then there's the patients that stay on and are treated to progression, which we believe the median would be about 8 months. And if you sort of do the math across those 3 populations and estimated time duration of treatment, that gives you to an average of 9 months on therapy for any given patient. And so if you look at the total population of KMT2A rearrangements across AML and ALL the incidence is estimated to be about 2,700 patients a year or 10% of those SEER incidents for AML and ALL and a very high percentage of those patients will unfortunately relapse. The current assumption is 2,000 patients a year. We'll get to relapsed/refractory 9 months of treatment across those patients. And then the price point today, the other targeted therapies are around $35,000 a month. We anticipate pricing at parity or slightly at a slight premium to that. So somewhere between $30,000 and $40,000. If you do that math, you get to around $750 million.

And then just maybe to focus in a little bit on timing, I guess, what are your expectations for what an inflection could look like? Do you expect it to be more akin to a straight-line uptake or maybe a hockey stick formation?

Yes. It is a -- we think that there can be a very pronounced and aggressive uptake. But because -- some of it is because of what I just had alluded to, we have an approval in 1 population we have top line data a few months later in the next population, which grows the market considerably, and we'll have a data set available for physicians to start thinking about, do I want to use this as monotherapy or can I use this in combination with ven or chemo. And so all of a sudden -- and this is, I think, very distinct from any other launches, you have the ability to choose how you use this drug. And in a population of physicians who are very used to prescribing how they feel is most appropriate for their patients. And it's very customary to get drugs into the guidelines with smaller Phase II data sets versus having to wait for registrational trials. So I think we've showed evidence that there is considerable reason to believe that these combinations will continue to be generating very strong support for use of revumenib across different ways of treating patients. And I think because we're pulling together both KMT2Ar and NPM1, even ahead of launch, you're going to have only 1 drug available and multiple companies generating data showing the benefit of using a menin inhibitor, I think that's going to help us a lot.

I wanted to circle back on one of your earlier comments, Anjali. You asked what else can menin inhibitors do. And I'm curious, as the data are starting to evolve and you get a clear picture of things. What do you think, what role do you expect the menin inhibitors to play overall in AML or ALL, from frontline to maybe post-transplant maintenance. I guess what I'm trying to get at here is, can the class be foundational in this disease.

That's what we're hoping to show. Yes, I think there's strong evidence that it is synergistic with ven, which has become standard of care for almost all patients, whether they're treated in frontline is unfit or treated in second-line as relapse from intensive chemotherapy. And menin inhibition, I think Gus had a presentation about this last year at ASH. The enhancement of activity on top of ven. So both preclinically, but we're seeing it clinically, I think that helps build that foundational aspect. But also you've never seen the type of monotherapy data that we're showing in these very late-line patients. So I think there's going to be a very strong rationale that anybody with a HOX MEIS driven tumor. We know that's KMT2A and NPM1. Now we're starting to realize that it's also NUP98 and they're looking for other subsets that may also be driven by HOX MEIS. And if that's the case, it could build to an even larger bolus of AML and ALL populations.