Good morning, everyone. My name is Jason Zemansky. I'm one of the mid-cap analysts here at Bof A. Thank you so much for joining us on this, our last day of our 2024 Healthcare 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 two 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 wanna start out by saying thanks to B of A and Jason and Cameron for having us here today. Yeah, 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 mid-cap biopharma company. We have two products, and I'm gonna go in a moment describe why I think we're really a unique story. I mentioned we have two products pending FDA approval in the third quarter of this year. We have a PDUFA date first on August 28th 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, leader in the cGVHD space, and we were granted priority review and 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 twenty-sixth. So, you know, really uniquely positioned. We don't know of any companies our size with two 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.
Well, 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?
Yeah, maybe I'll take that, and you can add on, Anjali. So, you know, we, I'll talk about the launches, but maybe also mention that the approvals that we're waiting for this year are just the beginning, we think, of the opportunities for both these products. I mentioned. I'll 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 a 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 menin 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, sNDAs and NDAs, typically, they're approved before the PDUFA date. So I mentioned the PDUFA date that we have is September 26th.
We are, I wouldn't say, expecting an earlier approval, but hopeful for an earlier 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's approved. So, the commercial infrastructure that we're building will be ready to launch in the third quarter, whether that, you know, 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.
We will be ready for a Q3 launch. With respect to axatilimab, I mentioned that we are partnered with with Incyte on that program. They're 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 forth 30% of the commercial effort in that 50/50 U.S. commercial partnership. You wanna say anything?
For revumenib, you know, I have to imagine that there's already a considerable advantage here, given that, you know, as you mentioned, this is a new class. It's novel. There's a lot of buzz following your presentations at ASH in December. You know, 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?
Yeah, maybe I'll, maybe I'll start there. I think it's, 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 their 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, you know, cross the hurdle of tumor coming back. So the goal here is to get patients for all physicians, the guidelines have pushed physicians to identify KMT2A rearrangements from the beginning, even though there was never a 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 transplant 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, you know, last year at ASH, you mentioned our data sets that we presented. I think we put together such a fulsome series of information, both in KMT2Ar, but also NPM1 mutations, which is another area of AML that does not have a targeted therapy available. And we showed really strong, very consistent data in that population as well.
We also had three different combination trials that we read out in 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, to that bolus, or sorry, 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 was it was not adding any toxicity.
If, 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, you know, 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 in NPM1. That can also lead to—y ou know, 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 to Ven or given as monotherapy is a welcome addition for NPM1 patients. And further, 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.
Yeah, 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.
Yeah, thanks. So, you know, you've guided to an addressable market of around $750 million in the KMT2A rearranged relapse refractory setting. I'm just curious if you could maybe touch on what some of your assumptions are here and, you know, realistically, how quickly you could get there.
Yeah. So, so the $750 million was for all, if you treated all patients with KMT2AR, and, you know, the, the goal would be to try to get there. I think even Tagrisso, which has 90% of the market, is not at a 100%. So there's always, you know, I'm not saying that we're gonna get $750 million in revenue to Syndax, but that is the potential. As we know, the dataset and the landscape right now, what we think could be achievable. The, the way we get there is just looking at the data that we've presented, last year in our top, you know, the, the data from our pivotal study in KMT2A, which showed, two-thirds of patients responding to treatment.
We also know that that dataset was collected in a pretty late-line population, so it was patients with a median of 3 prior therapies, so fourth-line patients on average. When we speak to physicians today, we're hearing that this is their treatment of choice in the second line. After a patient has 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 gonna reach for revumenib. So that's a much earlier line patient. They're probably not gonna see, have or have had as many transplants as they had in our dataset, and they're going to be fitter. You know, 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 two-thirds respond and one-third did not respond. The third that didn't respond on average were on treatment for three cycles. Of the two-thirds 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 and additional patients with the opportunity to elect to come back on at the time of data cutoff.
But there's the, you know, 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, you know, sort of do the math across those three populations and estimated time, duration of treatment, that gives you to an average of 9 months on therapy for any given patient.
And so, you know, 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 incidence for AML and ALL, and a very high percentage of those patients will unfortunately relapse. The current assumption is 2,000 patients a year will get to relapse refractory, 9 months of treatment across those patients. And then the price point, you know, 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-$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?
Yeah, it is. 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 one population. We have top-line data, you know, a few months later in the next population, which grows the market considerably, and we'll have a dataset available for physicians to start thinking about: Do I wanna 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 many 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 datasets 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 one drug available and multiple companies generating data showing the benefit of using a menin inhibitor. I think that's gonna help us a lot.
I wanted to circle back on one of your earlier comments, Anjali. You know, you asked: What else can menin inhibitors do? And I, I'm curious, you know, as the data are starting to evolve and you get a clearer picture of things, you know, what, what do you think, What role do you expect the menin inhibitors to play overall in, in AML or ALL, you know, from frontline to maybe, you know, post-transplant maintenance? I, I guess what I'm trying to get at here is, can the class be foundational in, in this disease?
That, that's what we're hoping to show. Yeah, 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 as unfit or treated in second line as, you know, relapsed 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. If that's the case, it could build to an even larger bolus of an AML and ALL populations.
Great. Switching to clinical development, as you mentioned, you have a number of combination studies ongoing, BEAT, SAVE, 102 , all at ASH. I'm curious, you know, you mentioned you're going to have the NPM1 RR data right after the launch, presumptive launch. In terms of looking at the pace of catalysts thereafter, when should we expect updates from these studies?
Yeah, I think we had guided across 2024. We will have updates from the trials at the EHA. Abstracts were published earlier this week, and you know, they announced that AUGMENT-102, the chemo combo, will have an update at EHA next month, and also the BEAT AML trial will have an update at EHA next month. You know, the abstracts include a data cut from very early. I think it was a January abstract. You had to submit your abstracts in way, way back in January, so I think we'll have even more data than maybe what's in there today. But and then the SAVE trial continues to expand, and Gus is very eager to get that data out. So I don't think it'll be at EHA, but I'm sure it'll be coming.
And Jason, if I could just remind your audience that we have an ongoing combo trial with Rev plus 7 + 3. We initiated that trial earlier this year, and our guidance is to initiate a pivotal combo trial with Rev and Ven/Aza by the end of the year.
Great, that's actually a great segue to my next question, you know, in terms of combinations, what are you prioritizing here? What's most interesting to you, especially as we get out of maybe the Ven/Aza and 7 + 3 in frontline?
Well, I think those two that you mentioned are the foundational drugs for anybody diagnosed with AML. And so in order to address or provide access to the largest population of patients, those two combinations are sort of prerequisites. And we're very focused, as Keith mentioned, getting to label expansions in those combinations. We're also doing work with investigators and under investigator-initiated trials to expand into other combinations. There's other chemo combinations being tested. There's a couple trials that are just starting up in combination with FLT3, midostaurin, and gilteritinib separately in relapsed, refractory and frontline, respectively. And I think and we have the Inqovi trial going on. Inqovi is an oral agent approved in MDS, but building their data sets in AML and enabling physicians to treat with an all-oral regimen.
They had data at ASH last year in frontline and relapsed refractory. They're continuing to study multiple combinations with Zospata and revumenib. So I think that could be another very important combination regimen going forward. It just helps patients sort of live their-have more of their quality of life without having to go for IV AZA infusions. And so, yeah, and then we just continue to work with thought leaders, like, where do you want to see these combinations? What would be impactful for you? How can we make sure you have all the evidence you need to insert revumenib into your version of patient care? And sometimes we're doing it through Syndax-funded trials, and sometimes we're providing drug for investigators to do that.
Great. Wanted to move past liquid tumors for a second and look at the opportunities perhaps in solid tumors. You have a phase I ongoing in metastatic colorectal cancer. What makes this indication attractive, and what are you looking for in terms of response rates that would give you confidence about, you know, expanding overall into solid tumors?
Yeah, I mean, I think we saw some really exciting preclinical data, showing that MLL interacts with beta, with the beta-catenin pathway, and either through CRISPR knockouts or small molecule inhibition, if you shut down that signaling pathway, you could block tumorigenesis. And it seemed like, you know, we knew revumenib was a very well-tolerated agent. We know that late-line, CRC has high levels of upregulated beta-catenin. I think it's 85%, 90% of patients are expected to have that. And unfortunately, the drugs approved in that setting are extremely toxic and provide minimal benefit to patients. You know, PFS improvements on the order of 4-6 weeks, response rates of 1%-2%. You know, it's sort of the hurdle was low if you could bring a well-tolerated agent that could improve quality of life and, efficacy for those patients.
That seemed like a pretty decent opportunity, given that there's such a large population there. And beta-catenin is also implicated across many other solid tumors, so this might be a way to just understand what the, you know, additional opportunities could be. So we're trying to be efficient with our resources and capital, but if that really is a path to explore, it's hard to turn away from it. So the phase I is, you know, both establishing safety and dose escalation in CRC, and then we're looking to see either, you know, complete responses or significant partial responses, or prolonged stable disease, because most of these patients will progress very quickly. So I think if we see evidence of either one of those, we can go forward, but we'll be very diligent about how we spend our resources.
Makes sense. So very exciting opportunity for Revu, to the point that I think it often overshadows axatilimab, which of course also is on the docket for approval here. I know we don't have much time left, but maybe, you know, it has a unique MOA. How does that impact the opportunity there, especially for, you know, especially, more refractory patients?
Yeah. No, thank you. You're absolutely right. Axatilimab always gets the short shrift. I think we have 10% of our time left, and we've turned our attention to that one. But, you know, we are, at Syndax, equally excited about the potential for that molecule. We're talking about a chronic disease that really, until three years ago, had nothing approved to manage those patients, and it was an unfortunate consequence of stem cell transplant that 40%-70% of patients could experience chronic graft-versus-host disease and no cure. And so it was exciting to see the sort of activity with axatilimab in that population. Our clinical trial, pivotal trial, enrolled an extremely late-line patient population. Patients had had a median of four years of diagnosis from GVHD.
You know, it was fifth-line patients that were enrolled, even though it was any two or more lines of therapy, and 80% of them had severe GVHD, and yet the response to therapy was incredible. The overall response rate was 75%. The time to response was just over one cycle, so they were getting fast responses. The patient-reported outcomes were, I think, close to 85% of patients were reporting feeling better, even though they've been struggling with this disease for a long time, and they were seeing that within a month of therapy. So it was— Physicians and patients were extremely excited to take this agent. The discontinuation rate in our trial was 6%, which is significantly better than we've seen across any of the populations, even though it's a very fragile and severe patient population.
We saw responses across every manifestation of GVHD, and you could argue, even more pronounced, you know, its cross-trial comparison is not appropriate. But you know, we hit numbers better than what we've seen across any of the other trials. So I think it's generated a ton of excitement. The differentiation of the mechanism, I think, is lending an ability to show an impact before or after any of the therapies that are out there, which is substantial. And it's because both the BTK-like ibrutinib, Jakafi, and Rezurock are all targeting T and B cell signaling, whereas we're targeting a completely different cell type that's not only involved in inflammation but also plays a major role in fibrosis, which is unfortunately what leads to organ damage and patient death.
And so the ability to reverse and manage fibrosis is something that isn't really available to physicians and patients, and I think that's what's gonna give axatilimab its edge, to really help change the course of treatment and hopefully disease.
Maybe real briefly, Keith, one last one for you. Commercial synergies. Patient populations are similar, prescribers might be similar here. Can you benefit axatilimab, Revu?
Yeah. Thanks, Jason. Yeah, it's one of the reasons that we opted into the co-promote exercise, the option that we had to put forward 30% of the commercial effort. We're gonna deploy a sales force that's focused on a revumenib prescriber audience. But the transplant specialists are a subset of the hemoncs that we're gonna be calling on that are the revumenib targets. So it's a perfect overlap for us, and with the 50/50 partnership we had with Incyte, just made total sense.
Yeah, great. Well, I'm afraid we're out of time, but you mentioned this is a very unique story. I think it's also a very exciting story, so really looking forward to seeing what happens next. Thank you both for joining us.
Thank you, Jason.
Thanks for having us.