Okay. Hi, this is Yigal Nochomovitz. I'm one of the biotech analysts at Citi. This is the continuation of our virtual oncology summit in February. It's my pleasure to have with me from Syndax Pharmaceuticals, members of senior management, including none other than Michael Metzger, the CEO, the CFO, Keith Goldan, and Briggs Morrison, President, Head of R&D. Gentlemen, thank you so much for taking a few minutes out of your schedules to chat. We really appreciate it. Maybe Michael, if you wouldn't mind, just for those less familiar with Syndax, just to give us a quick elevator pitch, two to three minutes, just highlighting the focus of the company, your key objectives, the key programs and some of the key catalysts that you're anticipating for the balance of 2023. Sure. Thanks, Yigal. Thanks to you and the Citi team for inviting us today. It's always a great opportunity to speak with you and share our thoughts on the company. I'd like to just start off by saying we're in a really unique position today. Syndax is advancing two pipeline agents with ongoing pivotal trials with data and potential regulatory filings in 2023. Potential approvals down the line in 2024. A very exciting time for the company as we look to transition to a fully integrated commercial stage company. Before we get to that, we'd like to talk a little bit about both of our assets, which are poised to be both first to market and best in class targeted medicines within the heme space. Addressing multi-billion dollar market opportunities. What we're first and foremost probably going to spend most of the time talking about today is our menin inhibitor, which will be the first, we believe, the first menin inhibitor approved. It will be the only one to have two indications, specifically KMT2A and NPM1. We're talking about relapsed refractory acute leukemia. These are two specific areas of acute leukemia that we're focused on with this agent. To our best assessment, we'll also be first and first to market for NPM1. Really exciting agent for these patients who have, you know, high unmet medical need. The second agent we'll talk about today is axatilimab, which is a first in class monoclonal antibody targeting CSF-1 receptor. Essentially no competition on that mechanism for chronic graft-versus-host disease. Again, relapsed refractory disease there as well. Longer term, we're excited that both of these programs offer potential for very broad franchise opportunities beyond these initial registration indications that we just described. We're also well capitalized. Our company raised $172.5 million at the end of last year, which brings us to roughly $500 million pro forma cash as of today. We'll be able to deliver with the balance of cash on the balance sheet, be able to deliver significant clinical and regulatory milestones. Launch both of these products, as described and also execute on selective business development transactions, which, as many of you know, is the basis of our business model to bring in additional molecules through licensing or acquisition, and that would be the early pipeline. All in all, a very exciting time to be at Syndax and be a part of this story as we move very swiftly towards getting drugs approved. Michael, we lost your audio. Sorry, do you hear me? Yeah. Maybe go a little closer to the mic. Sorry about that. We expect to have, you know, a really exciting year as we advance these molecules towards approval. Okay, maybe I'll pause there and hand it back to you. Thank you. Sure. Okay. let's obviously start with revumenib. What are the specific objectives for this year? What are the specific milestones in terms of data and development there? Right. You'll have to interrupt me if you lose my audio again. Let me start with AUGMENT-101. I'm just wondering maybe if you turn off your video it might help with the bandwidth. Sometimes that's an issue. Yeah. If you don't mind. Sorry. Not at all. Hopefully, that helps. Yeah. Okay. Where I was starting is AUGMENT-101, which is our pivotal trial. I'll start with that. This is our pivotal trial enrolling our relapse refractory adult and pediatric patients. As many of you know, it comprises three separate trials, KMT2A AML, KMT2A ALL, and NPM1 AML. 64 patients, adult patients, and up to 20 pediatric patients in each of these separate trials. Each of these trials could serve as a separate regulatory filing supporting approval. In terms of timeline, timelines and milestones, the first of the three trials will be enrolled by the end of the first quarter of this year, with top line data coming in the third quarter and the first filing in the fourth quarter of 2023 this year, then approval in 2024. Just a reminder, we've not yet guided as to which of the three of these trials will enroll first. We think more broadly about the development program, so that was relapse refractory disease and our potential of first approvals. We move on to what we're doing in the frontline setting with Beat AML and the INTERCEPT trials, and I'll describe those. I'll come back to what we're doing with AUGMENT-102, which is a relapse refractory-First. Beat AML is an umbrella trial in collaboration with The Leukemia & Lymphoma Society. It's part of a collaboration that revumenib's really the first menin inhibitor to be included in the trial to be combined with venetoclax and azacitidine in newly diagnosed AML patients who are unfit for induction chemotherapy. The trial will assess safety as well as initial efficacy. Initial data from this trial will be available, we expect by the end of the year. In terms of the INTERCEPT trial, it's a trial designed to explore the activity of revumenib in patients with AML who have MRD positive disease, and it's being run by the Australasian Leukaemia & Lymphoma Group, and it's now enrolling patients as well. The trial will enroll patients with measurable residual disease progression following initial treatment. As many of you know, that's a group of patients with very high risk of relapse, and it represents a very important unmet medical need. Lastly, the AUGMENT-102 trial is designed to assess the revumenib in combination with standard salvage chemotherapy, and it's a regimen typically used for pediatric patients, although adult patients may receive it as well. This is geared towards relapsed/refractory ALL and AML, and that trial will have initial data in the later part of 2023. Those are three really important trials. We are looking at some additional trials as well, which we can get into more later. Okay. just to clarify, for AUGMENT-101 with the three cohorts, that's 64 total, correct? 64 per arm. There's three separate arms, right? Okay. Yeah. There's two KMT2A arms, one for AML, one for ALL, and one for NPM1 AML. Each of them have the same amount of patients, right? 64 adult patients, up to 20 pediatric patients. They enroll separately. In fact, all three of those trials are enrolling at each of our centers worldwide. They, you know, each of them can be sufficient for potential approval in those indications. As I said, that they're all enrolling now, and we'll have the first of the three fully enrolled by the end of the first quarter, data in the third quarter, a first filing by the end of the year. I actually just got a, an email question from an investor. I think just to clarify, so I think you mentioned that you're attempting to be first to market in NPM1. The question I got was just in terms of prioritizing enrollment for those three cohorts, which is why I was asking about that earlier. You know, are you prioritizing the NPM1 AML cohort in terms of enrollment for AUGMENT-101? I think the question basically is, you know, where would we get data first with MLL-r or with NPM1? Yeah. It's a good question. As I was mentioning earlier, we haven't guided yet to which of the, whether it's KMT2A or NPM1 we'll enroll first. All of them enroll separately. You can think of them as separate patient populations enrolling at each of our sites. There's no particular priority between the three. I would say it that way. They're all equally opportunistic, and we can have patients flowing into each of the three arms. Okay. And just to clarify as well, the top line data in the third quarter for the all three or just not necessarily all three? Just could we just clarify? Right. We said the first of the three. First of the three. Okay. Filing in the fourth quarter. That's interesting 'cause that's quite a very efficient turnaround time to have the top line in the third quarter and file in the fourth quarter. Could you just expand on that? 'Cause that's fast. Yeah. No, look, I think the way we think about it, timeline is we follow these patients for six months, following last patient, last visit. That gets us into some time in the third quarter. Turning around a quick filing and putting the filing together by the end of the year, I agree is efficient- Yeah. We think it will. Okay. You talked about some of the other trials, the Beat AML, the 102 and INTERCEPT. Do you think you're gonna go into first line for revumenib at this point? Right. The Beat AML trial is a frontline trial. That's initial safety portion of that trial, but it's looking at patients that are unfit for chemotherapy consolidation, and instead are getting Venclexta generally standard of care. This would be a combination with Venclexta to see if we can improve on that regimen. That is in fact our one frontline trial that is starting or has started, and we're enrolling patients. Then there should be fit population. Generally, those are patients who get 7+3 consolidation treatment. That is a large, slightly larger population than the unfit population. We'll be looking to put a trial in place sometime in the near future. Yeah, sorry, I should have been clearer. I was referring to the fit patients. Nonetheless, with Beat AML, if that was positive or productive, I mean, would you then need to run your own study, or would that be enough to move forward with the drug application? Yeah. It's... The way this is designed, it's a phase I that leads it to a phase II/III. That phase II/III could serve as a potential regulatory filing. Okay. That's something that, you know, you know, is an open option to us. We could additionally do a company-sponsored trial as well. There's some options open to us. The design is such that we have the opportunity to go into a registration trial following the phase I. Okay. Wow, I'm getting a lot of very specific questions from investors, which I guess is great. There's a lot of interest on axatilimab. Let me see here. We'll come to those later. Okay. We'll get to that later. I think you answered the question about the prioritization. In terms of efficacy metrics, you know, what should people be expecting in terms of how to think about the bar for 101 relative to what's already been disclosed based on the phase I data at ASH last year? Right. look, I think the ASH dataset was rather robust. As you'll recall, it was 68 patients, 60 of whom had the either KMT2A or NPM1 mutations. I think the idea here is that, you know, that dataset kind of 30% CR/CRh rate was very competitive with other targeted therapies. I think the bar, when we talk about bar, you know, there's bar of approval, which obviously the regulatory bar, where you've seen drugs, other drugs be approved that were within the AML space with a CR/CRh rate of about 20%, and a median duration of response of 4.6 months at the low end, all the way up to, you know, roughly 30% CR/CRh rate, as well as, you know, seven, eight months of median duration of response. I think what we've shown at ASH, 30% response rate and median duration of 9.1 months was very competitive with that. Certainly to be first the best in class, we think this is representative of such a profile. I think the idea, the hope, with rather the phase II pivotal trials being similar in inclusion criteria and protocol to what we had in the phase I in terms of having a certain number of patients as well as the demographics and so forth that we're gonna be including in phase II we expect we should have similar results as what we've seen in the phase I. One key difference being that patients who have received a stem cell transplant, and, you know, following treatment for revumenib have the opportunity in phase II, where they didn't have necessarily the opportunity on protocol to go back on revumenib, which could extend the median duration that we see in these patients in a pivotal trial. That's one you know, and I think an important difference that we may see in the trial that could lead to slightly, you know, slightly better results. But ultimately, we think that not only is the bar achievable, the regulatory bar, but we think the bar that we've set with our efficacy, safety, as well as median duration response is quite competitive and should be really, you know, strong for us in this setting. Actually, that's interesting. That was my next question. If they go back on after transplant, I mean, obviously that would be great for the commercial, but in terms of how does that work in terms of counting duration? Does it just basically gets tacked on at the back end, or how does that work from a data capture perspective? Right. Patients are not censored for transplant. The way it works is we follow patients to relapse. In terms of they have treatment, they go on treatment, they stay on revumenib. At the time of relapse, that's the point where they come off trial, and that's the time of duration. If they have a transplant, during that period of time, they're counted as, you know, not relapsed yet. Right. They're still in remission. Until they, and whether they go back on therapy after they've been grafted and transplant or they just stay in remission, that's all considered part of the timeline for duration response. Not to be too specific, but I guess I'll ask. I mean, when you do count it, do you count the intervening time when they're going through the transplant as part of the duration, or You don't count that time? You do count that time. You do? That's included in the time of the duration. Interesting. Okay. Very interesting. All right. By the way, that's included. That's part of the guidelines, you know, the FDA guidelines that talk about how to, you know, score remission and score duration response. Okay. I guess more just of a biology question. I mean, obviously, as you've already highlighted in KMT2A and NPM1, I mean, these CR/CRh responses were very similar at the recommended phase II dose. I mean, is that consistent with your view and understanding of the biology in these two different mutational subsets that they would be similar? Sure. Maybe I'll ask Briggs to jump in. Take that. Yeah. short answer to that is yes, Yigal. You may remember when we started the clinical program, you know, our hypothesis all along was that the activity would be roughly the same in KMT2AR, used to be known as MLL-r and NPM1. You may remember when we first started the program, people used to ask us a lot about NPM1 because we didn't really understand at the molecular level exactly how revumenib worked in NPM1 disease. I used to joke that there's post-docs and graduate students all over America trying to figure it out. Well, they've made a lot of progress, and there's actually been a couple of very nice papers come out, came out last year, which now shows us in more detail the molecular mechanisms of why revumenib works in NPM1 disease. At the beginning, we thought they were gonna be roughly the same. The clinical data is showing us that they're roughly the same, and the science has now progressed where we really understand why they're roughly the same. Okay. You know, another question we get a lot covering the stock, just with respect to the. You know, how to think about the MRD negativity endpoint, in conjunction with the sort of a CR/CRh, type endpoint. You know, what is the From the clinical perspective, you know, how much do docs care about the MRD negativity and then, you know, going beyond that and getting the CR/CRh? Briggs, you want to take that? Yeah. Sure. So remember, just to clarify that, we talk about overall response. Overall response is basically when you repeat their bone marrow, do you see any leukemia in the bone marrow? That's the overall CR rate. Mm-hmm. The CR, whether you call it a CR or a CRh or a CRp or an MLFS, that all has to do with what else is going on in the blood counts. A full CR is there's no leukemia in the bone marrow and their blood counts are normal. A CRh is there's no leukemia in the bone marrow and their blood counts are at least half normal. A CRp means that your white count has come back, but your platelets are not yet normal, and a CRi is the opposite of that. Those are all sort of clinical ways of scoring how the patient's doing. The FDA has landed on CR plus CRh essentially because they're saying if you have no leukemia in the bone marrow and your blood counts are normal, or if you have no leukemia in the bone marrow and your blood counts are half normal, you're basically in good shape. You're not gonna have bleeding. You're not gonna have infections. You're not gonna need transfusions. Clinically, you're doing well. MRD negativity is a different way of looking at this, and that's when we take the bone marrow and we look and say, "Is there any leukemia left?" You can look under the microscope, and that's the standard. Standard CR means by microscopic analysis, there's no leukemia. There are more sensitive tests, and these more sensitive tests can look for a much, at a much more, the specificity is much greater for Are there any leukemic cells? The reason that physicians use that is primarily to see how deep is the response. If I look and I see no leukemia under the microscope and I do a really, really sensitive test and I still don't see any leukemia, that means I've gotten a very, very deep response. That's what I think, when you hear Dr. Stein talk about our the clinical implications of our data at various sessions we've had with him. He points out it's uncommon for these the previous targeted agents to give you such deep responses. That's why we emphasize the MRD negativity. The other point around MRD negativity is it's been well demonstrated in multiple studies that if patients go to transplant, the ones who are MRD negative do much better than the ones who are not. If you have a CR under the microscope and you're MRD negative, those patients tend to do much better when they go to transplant. MRD negativity is not a regulatory endpoint in the construct that we're applying, but it is quite important to the physicians to say how deep is the response they're getting from our drug. Okay. It's sort of a different metric. Is it a even higher standard, or that's not the correct way to think about it? I think it is the correct way to think about it because it's. As you saw of our CR/CRh patients, about 80% of them have MRD negative, some of them don't. It is a higher standard of I've really gotten rid of the leukemia, and the blood counts have all come back to normal. That portends a good outcome for the patient. We're getting more questions from the clients. Another one on transplant. Just someone's asking about. Can you just kinda comment briefly, how long does the actual transplant take? You know, the sort of the percent of time on drug, relative to the starting of therapy to the time you eventually come off. I mean, there's that period where you're not taking the drug when you're doing the transplant where it's still counted, as you mentioned, Michael. How. I'm just curious, how long does the transplant part actually take so people can understand the true time on drug? Yeah. Briggs, do you want to? Yeah. again, a bone marrow transplant is essentially intensive chemotherapy, and then a reinfusion of bone marrow from a donor. There's a relatively short period of time, maybe, you know, four to six weeks, where the patient is waiting for those blood counts to come back to normal from the transplant, and then they go back on drug. It's the vast majority of the time they're on drug. Another question just related to duration of response and the potential for that duration to be even better in the pivotal versus the phase I. If you I don't know if you talked about this specific slice of the analysis, but for the patients who were able to go to transplant under the adjusted protocol in the phase I, if you just look at those patients, what was the duration of response for them? Right. Well, just to clarify, the patients that went to transplant in the phase I were not able to go back on drug during the phase I period. We were able to get, through compassionate use, some patients the ability to get back on drug post-transplant. Right. The vast majority were not able to, you know, accommodate that way. The phase II portion of the trial was set up in order to accommodate that. These patients were able to. If the physician thought that they were and they had a donor ready to provide, they were able to go, you know, get their transplant and then go back on drug thereafter. That'll be something that the experience we'll see in the phase II. Obviously we haven't seen that data yet. Sorry, the rest of your question, Yigal? No, no. I think you answered it. Okay. That makes sense. Then, sorry, there's so much interest from the investors. These are some more questions. Someone's curious about Breakthrough Therapy designation. For NPM1, you know, once you have more than 20 evaluable, would you potentially be seeking that BTD designation? Yeah. Look, it's possible. I think we generally don't comment on our regulatory, you know, status and where we are with things. I think the idea being that I think the person asking the question had it right. You need at least 20 patients, and you need sufficient follow-up on those 20 patients. Obviously, we didn't have that in the phase I experience. We only had 11 patients, NPM1, within the phase I. Obviously, we'll have more than that. We'll have sufficient number in phase II. That's, you know, an ongoing trial, and so we'll have to see where we are when we can apply for that. Okay. Okay. That would be at least 20 at the RP2D. Correct. Yeah. Okay. That makes sense. And then, Hmm, this is a complicated question here. I guess you've kind of talked about this already in terms of the ordering. We don't know exactly which... Yeah, you're not prepared at this point to sort of say what the order of events would be in terms of approval in KMT2A versus NPM1 at this point in time, is that? That's correct. Yeah. That's correct. At point, yeah. I guess someone is trying to ask about, Okay, well, what about guidelines and NCCN guidelines? Just talk about more generally, how that part is going to work and when would you be seeking that type of validation for both for KMT2A and NPM1? You know what, Briggs, do you wanna dive into that? Look, I think, Yigal, you know, we have, as Michael walked you through three essentially three parallel pivotal trials, MLL-r AML, MLL-r ALL and NPM1 C. As each one of those reads out, and we have a database that informs the benefit risk of the drug in those particular populations, that's when we would think about, you know, engaging in the NCCN guideline process. As Michael pointed out, the Breakthrough Therapy designation was for KMT2AR all-encompassing, independent of whether it's AML or ALL, adult or pedes. Obviously, if we were to get that type of an indication, we could approach the NCCN guidelines process with that data set. I know I keep coming back to this, but I know you can't commit to the order of events at this point, but do you think that there might be a point later in the year, maybe in the summer, where you'd be in a position to provide a little bit more clarity on which cohort or cohorts would be appearing first in terms of data for the third quarter? For sure. I think as we move into, you know, a little bit further into the year, we had said that we'll have the first of the three enrolled in the first quarter, right? I think you'll start to understand what the order of events will be based on, based on our reveal of which is first. Okay. Maybe just comment a little bit. You talked about efficacy quite a bit, but on the safety tolerability side of the equation, just talk about, you know, how you see your drug competing in the maintenance space on some of the key questions on safety, obviously QTC and differentiation syndrome. How are you feeling about that? Yeah, we're feeling quite good. I mean, I think we've had... Remember, these are, you know, relapsed refractory patients on average getting four prior lines of therapy. They've seen chemotherapy, targeted therapy and whatnot, and they're coming on our drug and doing really very well with a high response rate, very few side effects. We've tested, you know, I'd say a robust number in the phase I, 68 patients, 60 of which who have KMT2A or NPM1. You know, there's quite a bit of patient information at this point, and I think that what we've seen, you pointed out QTC prolongation is the dose-limiting tox, really the only dose-limiting tox that we see. And it's identifiable early on in treatment. We manage the dose adjust these patients if they have a Grade 3, and essentially it goes away, right? These patients are easily monitored for it. We know what we're looking for, physicians do, and through simple dose adjustment, they're able to, you know, achieve a steady state and get a response that's potentially long-lived, that they've been able to stay on drug, for, you know, to be shown out to over a year in many cases, and even up to two years so far. Really a long, you know, I think a very safe and tolerable drug to date. You know, there is, as you pointed out, differentiation syndrome, which others have seen in their programs. We've seen it too, Grade 2, not anything higher than that. You know, it's something that we manage with, you know, steroids and hydroxyurea. It's, you know, essentially very manageable and identifiable by physician. Hasn't manifested in anything more serious. With regard to QT, I'll just go back and say that it's. We've, you know, none of these patients have discontinued because of QTC prolongation. We haven't seen any arrhythmias or anything more serious besides that physicians would necessarily get concerned about. This is asymptomatic QTC prolongation, which I'll also point out that many of the physicians who treat these patients have seen with other drugs. This is not an unknown side effect of therapy, but it's one that's very manageable, identifiable, manageable, and reversible to a point where it doesn't matter, and patients actually don't know that it's happened. Overall, I think the safety and tolerability of the drug is quite good, and, you know, it's allowing patients to stay on for multiple cycles and do really, really well. Okay, got it. And yet another question from an investor on your filing strategy. Someone's kinda curious in terms of just again, going back to the order of operations, since these datasets might come in sequentially. I mean, is the plan to file whichever one comes first, whether it's KMT2A AML, ALL, or NPM1 AML, file on that one first, and then the others follow suit as sNDAs? Or would this be different and be more of like a rolling submission where they're all gonna when you get the first label from the FDA, it will encompass all three populations? Yeah. Briggs, do you wanna jump in on that question? Right. Because we haven't given you the, you know, which one's first, as Michael said, I'll answer it more in theoretic terms. If all three were to enroll, be done enrolling, and all three were filed at the same time, then we could get a label for the broad KMT2A population and NPM1 all at the same time. Mm-hmm. If one of the populations completed materially earlier than the others, and we decided to file that one, then the subsequent ones would be sNDAs, as you point out. Okay. That is very clear. Okay. Let's see. Just a little bit on that. We'll move to GVHD in a second. In terms of revumenib, I know you've done some initial work in solid tumors, can we talk about that, Michael, a little bit and the strategy there? Yeah. I think we had announced that we're initiating trial in colorectal cancer, metastatic colorectal cancer. This is something that we felt given that there was some recent really good science published that shows that the mechanism of action of revumenib could have an impact on beta-catenin, patient high, you know, augmented beta-catenin patients who, you know, that could be colorectal cancer, it could be other forms of cancer where beta-catenin pathway is upregulated. I'll ask Briggs to go a little bit more into the depth of the science here, but essentially this would be a signal-seeking trial, 20-30 patients. We hope to get some initial data this year. This is a patient population that is unfortunately rather large, in the metastatic colorectal area, 50,000+ patients, high unmet medical need. A couple of approved agents that don't have, you know, I'd say a good track record or achieve success. They're approved, but they don't have, you know, really, good disease control rate, somewhere in the 10%-15%, as well as, you know, I think they're not very well tolerated. I think the opportunity for revumenib is to have an impact, and we're looking to see if we can not only see some early, responses in this population, but also perhaps even stable disease, which as I mentioned, the disease control rate is low. A bar of, response, you know, somewhere in the 10% range or higher, would be actually be meaningful in this population. We'll be looking at that in a small number of patients and see if we see a signal. Again, it's not the main thrust of our program, but it's something that if it were to be successful, then we would follow on with additional, you know, phase II and phase, you know, potentially pivotal trials. That's a ways off. Right now, we're focused on, seeing if there's an early signal, and then we'll follow up with additional. You know, potentially an exciting area of science that could lead to other solid tumors, and naturally, that's a big expansion of this drug beyond what we're doing in leukemia. Maybe I'll ask Briggs, do you wanna touch on the science a bit? Yeah. again, just briefly, Yigal, I mean, I mentioned earlier that we've now learned a lot more about how menin inhibitors work in NPM1 disease. It turns out that this mutant form of NPM1 acts in the nucleus. It sits on a chromosome and turns on a cancer gene transcript profile that's very similar to what you see with myelofibrosis, with the fusion protein. It's quite interesting that in the colorectal cancer, it seems to be a very similar story, except it's not NPM1 that is sitting in, on chromatin and turning on a gene transcription profile. It's beta-catenin. It still seems to be dependent upon the menin-MLL interaction, just as NPM1 is. as Michael said, you know, we're testing to see if that translates in the clinic. If it does, if we see the same kind of clinical activity in colorectal cancer that we're seeing with, you know, a menin inhibitor in NPM1 AML, where roughly a third of the patients are getting these nice responses, I think that would be really, you know, quite significant for the patients with colorectal cancer. We're in the early stages. We don't know if it's gonna translate, but the science is actually very similar to the story around NPM1. That's why we thought it was important to explore it in the clinic. Okay, great. I wanna make sure we get to axatilimab, since that's a very interesting program which I don't think gets enough attention. Let's talk about the mechanism, the CSF1 mechanism. How is this differentiated, and how could axatilimab change the treatment paradigm for the chronic GVHD? Right. thanks for spending some time on axatilimab. We think this is underappreciated as a program, and I think that's an exciting place for us to focus some time. Certainly, this is a molecule which we've had really some very nice data come out of ASH, not this past year, but the year before, phase I/II data that really set up the profile as potentially differentiated from the other approved agents. I'll say that Just starting with the mechanism, it's focused CSF1R antibody, you know, focused on the macrophage, monocyte lineage. If you think about REZUROCK, the newly approved agent and launched agent from Sanofi, or Jakafi, which is Incyte's drug, our partner, these are agents focused on the B-cells, and ours is focused on, you know, the monocyte macrophage lineage, so it's distinct. What that means for us is that this is really a mechanism that is fundamental to the fibrotic process, and our ability to interrupt that process really could have a profound effect on the chronic graft-versus-host disease that we see in these patients. It's a multi-organ disease, so you see manifestations in things like the lung and the skin and the eye and esophagus and GI tract and so on. The ability to treat multiple fibrotic organs, is something that we believe this mechanism could potentially do, and we've shown those effects in our phase I/II trial, which I mentioned just a minute ago. I think the idea that this is a, this is a distinct mechanism, potentially combinable with these other standard of care agents, could be very meaningful. This is a drug that we're looking at in third line plus chronic graft-versus-host disease for our first approval, potential approval. The ability here is to maybe move up line into, you know, combinations with Jakafi, for instance, which there'll be a trial starting this year, to look at, how do you certainly bring down the utilization of steroids, which is first-line treatment, but has its side effects and drawbacks for a longer term. I think the idea here is can we fundamentally change the treatment paradigm not only with a new mechanism in relapsed refractory disease, but also in combination moving up lines and offering patients earlier intervention that could really help their disease. Okay. AGAVE-201 is the phase II pivotal that you're undertaking currently. Can you just review the design and everyone is clear, what should be the expectations for what would be defined as success in that trial? Sure. Briggs, you wanna jump in on that one? Yeah, sure. Again, just to remind folks, AGAVE-201 is a randomized trial where patients are randomized to two different doses of axatilimab that are administered every two weeks, and one dose that is administered every four weeks. It's either 0.3 or one every two weeks or 3 mgs per kg, every four weeks. These are relapsed refractory chronic GVHD patients, similar to what we enrolled in the phase I/II trial. Again, the top line data, the middle of this year. You know, I think again, from a, from a, your question, Yigal, about what is the sort of the efficacy bar here, you know, we presented, I think some, and published, some very nice data from the phase I/II program, which showed, you know, a very nice response rate in this patient population, competitive with other agents that are in this space, and Michael can comment more about that. I think the, you know, if we were to see efficacy and safety in AGAVE-201 that parallels what we saw in the phase I/II experience, I think we'd be quite excited about that, and we think it would provide, you know, a quite nice alternative mechanism, as Michael pointed out, for the treatment of these patients. Okay. Then it's interesting. Did I hear you correctly? 0.3 mg every two weeks, but 3 mg every four weeks. Just talk about. That's interesting. It's an order of magnitude higher. Yeah. there's two doses every two weeks, 0.3 and one. Oh, okay. Okay. Remember, the 1 mg per kg was what we did the phase II expansion. The data that we presented was sort of a phase I dose escalation and then a phase II expansion. That was at 1 mg per kg every two weeks. If you think about if you're gonna go every four weeks, a direct link from 1 mg per kg would be, instead of 1 mg every two weeks, you would do 2 mgs every four weeks. Right. Based upon the phase I data, we thought we might need to go a little bit higher. That's the 3 mg, every four weeks. We're looking at that just as a potential, you know, so a little easier regimen for patients instead of coming in every two weeks. Okay. One question we're getting online is how are you doing the statistical analysis when you analyze here the three different doses? How does that part work in terms of like the, is there an alpha split on the different doses, or is it not like that? No, essentially each one is, it, statistically, they're sort of each is a, they're like parallel arms. As long as an arm beats what is the presumed null hypothesis, and has adequate safety, then that is a potentially registrable dose. Okay. There's not a, they're not powered between dose comparisons. It's really each dose compared to its null hypothesis. Okay. Just going back to my question around the dose scaling relative to the timeframe as you were talking about. The phase I data, correct me if I'm wrong, but apparently the phase I data suggests, that actually the 3 mg per kg every four weeks may actually be less effective than the 1 mg per kg every two weeks. Is that true? If so, how does that translate into thinking about the phase II? Yeah. I wouldn't, I think the numbers are kind of too small to make any, you know, strong conclusions between the doses. That's why we're doing an official dose-ranging trial where we study enough patients at each one. I do think there was also a little bit of a trend that we might see a little more toxicity with the 3 mgs. Although you're giving it every four weeks, you are giving 3 mgs per kg, you know, on that day of dosing. That's why we're looking at this range of doses, as you pointed out. It is a nice range, and I think we feel very comfortable that within that range, we're gonna find, you know, a dose that gives a very favorable benefit risk for patients. Should the REZUROCK response rate in GVHD, I think it was 75%, at 200 mg QD through the cycle seven, in their trial. Is that a benchmark that is relevant here? Should we not be thinking about that as a benchmark? Yeah. I mean, it's one benchmark, you know. I think there's, you know, Jakafi, was in the, I think in the 50% range or a little higher than that. I think in our data was around, you know, 70%, 68%, 70%. It's, you know, we're right in that zone. I think that's, those are all, you know, really good results. You know, the key to this population is obviously, efficacy and tolerability. Patients tend to, none of them are curative treatments, and so the patients tend to see one after the other, they get sequenced. There's really no set paradigm for how these patients are treated after the front line. In other words, we've seen in our trial, in our phase 1, we had a handful of patients who actually had seen Jakafi and also REZUROCK before coming on our trial. We expect that in the real world, that once our drug gets approved, that it'll have, you know, utilization in the third line plus, but it could, you know, work out where the patients if they have certain manifestations or the experience is such that physicians become comfortable, it could be used earlier as well. There's, you know, the fact that these patients go from one to the next over their sort of five-year average survival time during their chronic graft-versus-host disease journey. I think that's, you know, a reasonably good setup for multiple drugs doing quite well in this space. As you've seen, the Sanofi drug, the REZUROCK drug has done very well in its first year of sales. I think roughly $200 million-$250 million in first year sales. I think this is, when you talk about, you know, benchmark of where they are efficacy-wise, I think that's important, that ultimate range that I just mentioned, but also the safety tolerability and, you know, ability to stay on therapy. Again, we are treating really heavily pre-treated patients, and they are doing quite well. I think all of that needs to be kind of factored in. Okay. Lots of questions on axatilimab which is great. What about secondary endpoints? How important are those to the value proposition? I believe you also are working on a sub-Q version. Where does that stand? Briggs, maybe you wanna comment on the secondaries, and then we can talk, as you mentioned, about the sub-Q. Yeah. Look, I think it's a complicated disease. You know, some of the other things we're looking at are can we taper off the steroids in patients, you know, as they respond so well to axatilimab? I think that is, you know, as you've talked with physicians, that's a critical factor. Steroids are the mainstay of the treatment of this disease, and yet they have their toxicity, so to be able to lower the dose there. I think the quality of life instruments that are used in this disease are also quite informative to practicing physicians. You know, we have a suite of secondary endpoints that will help round out the characterization of both the benefit and the tolerability of the drug. Michael, I'll let you take the other question. Right. On sub-Q, I think we haven't said much about sub-Q and I'm not gonna say much more here. I'll just say that it is something that, you know, is something that we're considering with our partner. I think the idea is that this is an IV infusion. As Briggs pointed out, the regimen is either once every two weeks or once every four weeks, depending on dose. I think, you know, this is, again, a very well-tolerated agent. Physicians, specifically in chronic phase of their disease, seem to keep a very close eye, high touch, patient interaction. The patients tend to be in the office relatively frequently. This regimen doesn't seem to be anything other than, you know, I'd say, manageable and convenient for patients. I think that's something that doesn't, you know, doesn't really factor in much. I do think the sub-Q, as we've looked at, we're looking at a 4-week dosing regimen, and sub-Q could potentially add to the convenience down the line. We feel, you know, quite strongly that this is a, you know, a very manageable, easy-to-administer regimen. What about some of the oral CSF1Rs, I believe. There's a company called Abbisko. Any thoughts on that in terms of competitive positioning? I believe they're working in GVHD, and they also had a breakthrough in a tenosynovial giant cell tumors. Right. As you know, CSF1 is not an undiscovered mechanism. Obviously, we're not the first to pioneer it, and we are the first to pioneer it in chronic graft-versus-host disease. I think the fact that we have an antibody versus a small molecule, our molecule is very clean, has a profile that we think is uniquely suited to hitting the target and also retaining patients. That's, you know, we think unique to antibodies such as ours. I think small molecules may have a little bit more difficult time dosing patients and deriving the type of efficacy and safety that we get with our molecule. You know, we're obviously well ahead of the field. There, you know, with success, sometimes you have competitors, and that's okay. You know, we feel like our molecule has some unique benefits and unique attributes that, you know, position it well versus the competition. Also just in terms of approvability and the strategy there, would you go for AA, accelerated approval here or a full approval? I believe REZUROCK got a full approval. Yeah. What's the plan? No, it's a full approval filing. This is, as you pointed out, REZUROCK was approved with a full approval as well, you know, as the other agents. I think the idea here is that this is a, you know, this is a trial that's in a lot of ways very, very similar to what REZUROCK completed a few years ago. I think, you know, based on guidance, based on our interactions with the FDA, this should be a full approval. Okay. Just to bring Keith into the conversation. Maybe just a quick recap of the financial strength of the company and the runway and how you're thinking about capital needs going forward. Yeah. I'll just, you know, Michael touched upon it in his opening remarks, I'll just recap that on a pro forma basis, we had $500 million on the balance sheet at 9/30. Our, we'll update that number obviously in our 4Q earnings, which is upcoming. We gave guidance that that $500 million pro forma was sufficient to get us into the second half of 2025. You know, combining that runway with the milestones, you know, clinical, regulatory, and commercial that Michael has been reviewing for the past hour or so, you know, gives us a confidence that we have enough cash to execute against our business plan, achieve, you know, all of the upcoming, you know, catalysts, milestones that we have in front of us and get us, you know, a year plus past an expected launch date. We have a little more time. Michael, just to close out, talk a little bit about what are you doing on the commercial side at this point? How far have you gotten in terms of thinking about how, what, how you would develop a launch strategy for revumenib? Then second, is there anything going on in terms of bringing in additional assets or you've got your plate full? I guess the last question is, you know, what is the one thing you think the street is missing here in terms of understanding Syndax? Thank you. It's probably three or four questions in one. I think, look, we're very busy this year. I think we're hiring incredible talent at Syndax, and have really put together a great team to execute on both of these first and best-in-class agents. In terms of commercial organization, we hired our Chief Commercial Officer, Steve Sabus. He'll be helping to expand our commercial team. You know, it's a very focused effort in leukemia. We do have two agents. One of the axatilimab program will be led commercially by Incyte, our partner. We have the opportunity to collaborate there and co-out, and we'll make that election closer to closer to the approval timeline. You know, essentially it's, you know, roughly 40 reps in the U.S. in terms of sales force. We are planning to commercialize ourselves in the U.S. Ex-U.S., we'll look for a partner when the time is right. you know, we do think just in terms of how we're positioning ourselves for launch, I think there are definitely some synergies we see between axatilimab and revumenib in terms of the sales force. we'll be working, as I mentioned, with Incyte in terms of our election and how that would work out. you know, essentially we have, you know, a program where we can bring both drugs to market, we believe, and then launch them successfully in the near time with a very focused effort around revumenib and potentially axatilimab as well. very exciting time for the company. What is the what is the street missing or what are people missing about our story? You know, I kinda hesitated there for a second because you start to get all these questions about axatilimab. And I would say that I think there's a tremendous amount of value to be created for both of these molecules. I think people don't fully appreciate how rare it is for a company less than $2 billion in market cap to have two filings in one year, potentially two approvals in the next 18 months with two first and best-in-class agents. I mean, that's a very rare setup. I think some people are missing that fact that I don't know that you can potentially name another company in this situation, so that's exciting. I was hesitating because of axatilimab, which you're getting a lot of questions on, but that seems to be a rather new phenomenon. Maybe people are catching on to axatilimab and that there's significant need in chronic graft-versus-host disease. I think until the launch of maybe Sanofi's drug, and the success that Incyte has seen with Jakafi in the space, I don't think the commercial opportunity was really appreciated for this agent. Maybe it was a little left behind what we were doing with revumenib, but I think we have two agents that are worthy of attention and investment. We're, you know, well-resourced, as Keith pointed out, to really take advantage of the opportunity. I do think that perhaps axatilimab is something to pay attention to as, you know, we said in the middle of this year, we'll have... I don't know if we talked much about the timing, but in the middle of this year, we'll have, you know, top-line data for that agent for axatilimab with a filing BLA by the end of the year. Again, not to be left behind or ignored, it's a big, a big, opportunity for us. Any comments on, you know, the pipeline expansion, BD efforts? Sure. Thank you. Yeah. Look, we think this is an important part of what we do. The reason we have two agents in the position that we do is because not only do we have a great team, but I think you have to get them first. Business development has been a focus from the beginning when Briggs and I came together several years ago, and it continues to be as such. We're looking for earlier stage assets. Targeted therapy remains a focus in oncology. Call it late pre-clinical and early clinical stage assets. The advantage there is, of course, that we can use our expertise to do translational medicine to bring these into the clinic and differentiate them through good R&D. I would say that they're relatively resource, not intensive, but I'd say they're able to be fitted into our pipeline. I think that's an area of focus for us going forward. We have a very high bar for bringing new assets in, so this is not something we take lightly, because our investment is certainly focused on our later stage assets at this point. We would welcome potentially bringing another asset or two in the not too distant future to complement what we have within the heme space or otherwise within oncology. All right. Perfect. Well, I think we used the hour very efficiently, got a lot accomplished, very comprehensive. Michael, Keith, Briggs, thank you very, very much. This was great, and I'm sure we'll chat soon with your, with your earnings. Thanks again. Thank you. Thanks so much. Appreciate it. Thanks, everyone. Appreciate it. Have a good day. All right. Bye.