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

Good morning, everybody, and welcome to Day 3 of the Goldman Sachs Healthcare Conference. My name is Chris Shibutani, member of the health care equity research team, and we are very pleased to once again have Syndax join us for our discussion a lot of progress here. But let's first introduce the cast, the character. I think the webcast tends to be only not video as well. So we're all sitting here in Miami in our bathing suits, but obviously, we have Mike Metzger, CEO and some additional members of the team. Maybe Keith, I'll start with you. Just tell us a little bit about yourself.

Yes. Thanks, Chris. Thanks to Goldman Sachs for having us, Keith Goldan, Chief Financial Officer. I've been with the company about 2 years now, and I'll turn it over to Steve.

Yes. So happy to be here as well. Steve Closter, Chief Commercial Officer at Syndax. I'm not quite at my 3-month anniversary. But happy to be here, working with a great team at Syndax and a pleasure to be part of this fireside chat today.

Very timely hire, a position extremely important. We'll be seeing and hearing a lot from you. Michael, you and I have gone back for many years, Syndax quite a journey, an exciting point at this particular juncture and a rare juncture to be at, frankly, for a small company in the biotech space, having more than 1 asset. I think if people actually do the screening and the scope of that, it's unusual, and it's quite a milestone achievement. Kind of like having twins. But give us maybe for the base purposes of level setting where you guys are at overall?

All right, well, first of all, thank you, Chris. It's a pleasure to see you. It's been many years working together. So -- and Goldman has done a great job with this conference and always like to be included and I appreciate that. Well, I would just start, it is a very unusual time for the company and a very special one where we're now in the cusp of being a commercial stage company with first-in-class, best-in-class assets, 1 addressing KMT2A acute leukemia and NPM1 acute leukemia. These are new indications for first-of-its-kind drug, a menin inhibitor, revumenib and we've had our pivotal data. We have PDUFA date as of end of September. We're under RTOR for that product. So the FDA has given us every advantage in terms of regulatory approval, and we're leveraging that to get the drug approved. We expect some time in the third quarter. Again, these are for patients who have a form of leukemia that's probably the worst prognosis in KMT2A, adult and pediatric patients. And so this is a very important milestone, not only for the company, but for patients as well and physicians who are treating them. We will have some additional data for that program in terms of a really important milestone beyond approval and that is for NPM1, it's the second indication. So the setup here for a new company, commercial stage company that will have not only a first approval and first-mover advantage into that market and a high unmet medical need, but then a second indication in NPM1 with data coming on the heels really within a very short period of time of the first approval and with a potential second indication approval in early 2025. So a very important new launch for that program. And of course, the second molecule, you mentioned 2. So we have another molecule it's axatilimab, which is a CSF1R inhibitor first of its kind in chronic graft versus host disease. This program is partnered with Incyte, and we're working very closely with them to launch that drug in the fourth quarter. The indication is extremely important. Obviously, these patients need additional molecules and additional medicine to treat them. And we see both, this opportunity in third line plus GVHD as well as expansion opportunities into the frontline setting in combination with Jakafi and some of the other standard of care agents who will start those trials later this year. So in summary, we have these 1st and best-in-class assets that we are pioneering here and we'll have approvals in the third quarter, followed by launches this year, and we're excited to be doing this.

Excellent. Let's talk a little bit about product profile, obviously, that is generated from the data, AUGMENT trial, we're talking about revumenib here. This is what is currently before the regulators and it's what's going to equip Steve and his commercial organization in terms of thinking about how to go to market here. Perhaps touch upon some key aspects, key selling points essentially for AUGMENT in terms of how you see the data and the profile addressing the unmet need.

Sure. So look, I think the data that we have in front of the FDA is from our pivotal trial in KMT2A patients. This is roughly 57 patients in -- that have either AML or ALL, adult and pediatric patients. And the data was, as I mentioned, first of its kind, very high rate of response rate in the mid-60s, so roughly 2/3 of patients clear the leukemia, which for this particular disease is very hard to treat. The endpoint of the trial was a CR/CRh, a complete response or a complete responsive path hematological recovery and we were at -- in the mid-20s. And this impaired, of course, the standard of care, which is less than 10%. So these patients don't do well. Some of them respond to treatment chemotherapy early in the treatment, but they relapse very quickly, and that leaves almost all the patients -- the entire patient population to be treated in the second line. And so we're talking about patients who are young and essentially physicians want to get them to a transplant as quickly as possible our drug has been able to demonstrate that. 40%, 50% of our patients have gone on to transplant once they respond. And then the key is after transplant, are you able to put them back on therapy in the maintenance capacity. And that is something that we've been able to demonstrate effectively in our trials and some of our other work outside this pivotal trial in compassionate use so we've been able to see this longer -- much longer duration of treatment and follow-up in the maintenance setting with patients in remission. So it's a new paradigm for patients where they've been able to treat these very young population with a terrible diagnosis, drive them to transplant using our drug and then put them back on therapy and keep them in remission and we've seen patients out for 3 years now on therapy. So that is very new and different. And I think the way the drug has manifested, and the way physicians are using it, will lend itself well to a commercial opportunity where standard of care does not work. And there's really nothing in the pipeline that will compete with this agent for any time in KMT2A. So it's a really good setup to start.

So obviously, there's clinical management paradigms that can be quite precise, but we're talking about some real unmet need some challenges that are there. So we're going to get we believe, in our house view and anticipated approval. And when you think about what the FDA will deliver to you, the label specifics, help us with boundaries for what would be satisfactory, maybe a potential better-than-expected outcome or some of the risks what are some of the boundaries on the label language when we get to the end of September, and you hand that over to Steve and his team is like, okay, go to market with this, just frame that.

Well, maybe I'll let Steve address that as he's the one who's going to be working with that.

Yes. Thank you. I mean, the label is ultimately the most important document we're going to have, it will form the basis for everything we say publicly. My experience even prior to coming to Syndax, companies and the FDA have the same goals, right? Labels that are based on the data that really outline the risks and benefits of a product. So I think we're very much aligned there. I don't -- we don't expect anything in the label from a class effect, black box and differentiation syndrome that is going to be any difference, warnings and precautions that are consistent with other drugs that have been in the space. I just amplify what Michael said around the story that we can tell through the data now, and we expect that story to be told in the label. It may not be as explicit that's fairly common. But we look at Section 14, the label, which is the clinical trial section. It will describe everything Michael said, in a narrative. It may not have all the metrics in there. But I think that the benefit that we have from a promotional standpoint, and this is well documented, you'll be able to promote based on what's consistent with the label. So we've got a story much like Michael shared that we've tested with commissions that really resonates. And end of the day, we think we'll end up with a label that's incredibly robust that will help us tell the story. And most importantly, we'll guide clinicians on how to use the product successfully.

The math on any revenue forecast that investment community has been doing very much depends upon this notion of induction and maintenance, right? To the extent duration at which the drug is going to be used. Talk about how you see the potential applications of label. And here is where the practice of medicine actually gets invoked more often in thinking about do you see the data that we have so far translating into actual commercial utilization. I know that Kevin and I and my team has always done work over the course of the journey of the clinical trial progress speaking with KOLs, and there's been a lot of optimism in terms of how they are anticipating using this. But what's a practical base case way to think about, in particular, maintenance utilization.

Yes, I can take a stab at that one. I think that is the gold treatment, and mind you my time here is limited 3 months in the role, but I've had the opportunity to be at a couple of executive advisory boards and met folks from MD Anderson and Cleveland Clinic and others and reviewed the research we've done to date. So exactly what you said, Chris, that's what physicians want to do. And it's often the drug that got them to transplant is the product they're going to use post transplant. Some of it's anecdotal. I think once patients get on something, you do not want to take them off if it's working. So I think there's a lot of momentum there. There's enough data that we've seen already publicly that will be likely mentioned in the label in terms of patients that have been on the drug. That should give physicians some comfort that they can do it. And some of this is going to have to play out in real time. But that is the instinct of physicians to do it. And we think that will lead to for some patients being on product for quite some period of time, right, and longer than we've seen with some of the analogs in the space.

And maybe I'll just amplify that a little bit. I think the additional data that's being generated is also very important in the practice of medicine such as newly diagnosed patients using it in combination with ven/aza, which is subject of some of our presentations coming up at EHA, and then later in the year, and the ability to dose successfully with those standard of care agents will allow physicians to understand how they might use the drug in other ways and more spontaneous use. So I think it's -- these are longer-term trials, but the ability to get this data potentially into guidelines could be very helpful to physicians in how they see the broader use of this agent outside of just KMT2A, NPM1 itself.

Yes. Here again, there's a lot of building blocks of sizing the opportunity. The initial indication is for the KMT2A. I think a lot of investors anticipate and put a fair amount of weighting into the potentially larger NPM1 population of patients there. Maybe Steve, help us with some numbers just so we have some perspective on the relative sizing.

Yes, happy to do that. I think often, we look back to analogs and how successful have predecessor's similar products in the space been and I think if some of those products were introduced to market now, there'd be a higher pricing carter to help them. And I think you need a type of population that you can extend treatment on. And I think we have both really in the menin space, particularly for revumenib. So I think from a numbers standpoint, in total, KMT2Ar and NPM1, you've got about 6,000 patients that are relapsed and refractory. Obviously, the front line is going to be maybe 1.5x that. But if you do some simple math, if you look at a pricing carter we'll say, $30,000 to $40,000 a month, a duration of treatment somewhere between 6 and 12. That initial opportunity is about $2 billion roughly for the compound. I think what makes it unique for revumenib in addition to, we'll say a large initial when I say that, that assumes an NPM1 launch. But it's really the sequence of the indications. And I think Michael really laid this out well. KMT2Ar is a terrible prognosis, right? We know when patients have that diagnosis. Their mortality rate is incredibly high. They need to be treated urgently. And we see that. We see that when we talk to KOLs, when we've done a research. And what makes rev unique is that you've got that second indication arguably within a year. And it's that type of launch momentum, we think that will really drive early utilization. When you talk about first mover advantage, you really -- you'd leverage that first-mover advantage by getting out of the gates incredibly strong, which I would say would get to my third point, these are not, we'll say, promotional efforts that are that large. Modest-sized sales team, promotional effort, which is unique because my experience is often in larger categories where there is a little bit of an arms race. The more reps, the more money spend, the more you drive success. I think this is a space where a company, small, medium and large sized can all compete because there is a point of diminishing returns. But our plans really for launch are to fully staff our teams, engage more than 95%, probably closer to 90% of the patient population and do everything the right way. So when we do enter the market, we're able to provide the best chance of success for patients and clinicians and really build, we'll say, some competitive immunity to anybody that may or may not come later in the life cycle of the compound.

And remind us where and what products that previous experience was that you bring to bear here, you made reference to it.

I did. So I mean, my experience is a bit different. It is in CNS, infectious disease, which is a smaller space, not quite as small, I think, as this -- but hospital-based infectious disease drugs with a lot of science, unique distribution systems, buying bill, things like that.

Right and how is your arm wrestling with Keith going as far as getting enough resources and checks for him to write to equipment your success?

Yes. I think that's funny. But I think as I've been here. I mean one of the reasons I came was clearly the leadership team and also the ability to resource what we need to do. So I feel very comfortable with what Keith does as well. I mean, we look at this as a great partnership. We're super careful about our investment choices, whether it's size of the sales team, size of the promotional investment, how we want to manage distribution. We do what's best really for patients and what's best for the organization, always keeping in mind what we need to spend to do that and just try to be as efficient and effective as possible.

Have you shared thus far what the battle plan is in terms of actual range of numbers of people that you're going to have on the outset and how that could build as you have additional data to signal the expansion opportunity?

It's a good question. We haven't given exact numbers. I'll use the, let's say, 30 to 50 range, somewhere in there, which I think is consistent with other agents that have been on the market. But I will say this. I mean the market is complex for patients. You can start in community oncology, get to academic centers. There's all sorts of stakeholders from physicians to nursing staff to pathology to reimbursement support to formulary decision makers and institutions. So we've aligned on a model that has a few different customer-facing roles that's able to really interface completely because that's what we think will lead to better success. And we are fully staffed. I mean, really, since I've been here, it's a plan for success. We have full faith in really both products, getting through FDA. We're very optimistic so we're fully staffed. So our entire sales team is on the ground. We hired them just over a month ago. I'll add this a little bit of a fun fact. I mean Syndax at least at the -- and this comes from a different perspective here. But if you're in this space and you're in sales, and that's your job, Syndax has been on the radar for many, many folks. So this is going to sound like a college entrance statistic. But we posted these roles back in February, we'll say between 30 and 50. We had 4,500 applicants that applied. So you got a better chance of getting into Stanford than you do of -- becoming a rep here at the organization. But these individuals are skilled, experienced, there's over 20 years of experience in hematology and oncology. They've been through 6 or 7 start-ups. And they bring not just success and experience but actual relationships. So when we talk about getting out of the gates fast, it's that and the fact that we've already put them in the field where they're profiling accounts, there's about 2,000 that we really focus on, and they'll know who's who, what's their -- how do they test patients for rearrangements or other mutations. So at the time of launch, we're not walking, we're almost running with the opportunity to make sure that the drug gets to as many patients as appropriate as possible right out of the gates.

No. And I think one of the things that's also more nuanced in terms at the respective sites that you're at, there's kind of 2 subspecies, right, the hematology/oncology crowd as well as the transplant physicians. And oftentimes, it's kind of reaching up to 2 sides of the beast, so to speak, and they need to typically work in some collaboration. There are some tension points about decisions which are typically made by disease management committees, but it's going to be very important to interface there. And then on top of that, the logic of the portfolio, you will be able to leverage. The indication expansion does not seem to necessarily mean that you're going to have to amp up to address a whole different group. And then further, there's the overlap -- and we'll talk a little bit more about axatilimab so that there's a thematic end market logic to what you have there, right?

Yes. I'll make a few comments on this. But I think you're touching on something that's very important. I think the synergy between the products, which really, we're calling on they are leukemia specialists, but the subset of that specialty is the transplant physicians. So you're not needing to expand to additional physician audiences in order to get the message out, right? So that allows us to have a focused field force in a dynamic one at the same time, bringing 2 products to bear, not 1, but 2 products to bear with additional data for the second very soon thereafter the first indication launch. So it's a very unusual set of circumstances where a new field force can be carrying 2 products in the bag, and we'll also be leveraging Incyte for their expertise in chronic graft versus host disease on the commercial side. So I don't know if you...?

No, your point, Chris, is really well taken. And I think we are sizing for the future almost. I mean I think because the headcount we're talking about, it's really small, honestly, in the space. So we're sizing for the NPM1 opportunity. We're sizing for axatilimab at the launch. And that was a conscious decision. And I think that's one where you feel great about your products, you feel great about the chance of regulatory success. You know enough about the market, what are the different levers, anytime you expand, restructure, you're just causing distraction. And we frankly need a customer-facing team that has no distraction that just has our unwavering support, put the right support in place, let them do what they do, which is customer engagement, really, at the end, supporting patient success. So that's -- that was a good point you made.

Yes. No, it is very much focused around centers of excellence. There's also kind of a notoriously opinionated KOL cabal in the leukemia world. So this is going to be a fun ASH as it always is, but especially with you guys out there on the market. Now investors that are very [Technical Difficulty] in the tech space specialists focused on data, the upcoming NPM1, let's frame that opportunity here. What do we know from the Phase I and what should people expect in terms of what incrementally objectively and where you're aspiring to demonstrate with that data by the end of this year?

Right. So just to reprise a little bit on the Phase I data. So this is in 14 patients at the RP2D. We had -- I would characterize our data as best-in-category data for NPM1 patients. This is an AML only, a 36% response rate, CR/CRh, 50% overall response rate, 100% of the patients who had CRC or got to the endpoint reached MRD negativity. So all the patients who got a response were in -- or got a complete response were considered MRD negative, a very important prognostic indicator for this disease and physicians pay attention to that. Several patients actually, about 45%, 43% went on to get transplant after getting a response, which is noteworthy because this is a slightly older population. And again, these are third, fourth, fifth line patients who are sort of out of options. And so to be able to transplant them at their age after having received other therapies is pretty noteworthy. So I would also say that the data that we've seen with KMT2A and NPM1 are very similar, right? So the others in our category haven't seen that, but we've seen consistency not only in terms of response rate, MRD negativity, transplant the ability to go back on drug and the maintenance capacity. We've had patients continuous, NPM1 patients on therapy in that trial in Phase I. And so we expect the data to be actually quite similar to what we've seen in NPM1, which was very good. I'm sorry, in KMT2A, which was very good. And again, there are slight differences in the patient population, mostly related to age and ability to, what they call, fit versus unfit that undergo transportation. But but we've seen great safety tolerability as well as efficacy in that population. So we expect the data to be quite consistent with what we've shown in KMT2A thus far.

The real benchmarking that people like to get specific on in terms of the CR rate and durability. So we have a backdrop about standard of care, and there's a competitive environment as well, other companies with assets there frame that dimension of what we should expect on that CR rate and durability comparison.

Well, I think we've established that our drug can drive patients not only to transplant, but you can put them back on therapy post transplant. We've seen patients on for 3 years plus in both of the trials and outside of the trials themselves in compassionate use setting. So I think we have this notion of durability based on the CR rate, which we'll have to see over time how that plays out. But we know that a 20% to 30% CR/CRh rate is sort of the range of what we would possibly expect and -- based on prior data, and I would say a durability in the 4- to 6-month range is certainly this is all approvable, if you will. And that's essentially what we've seen -- could we do better? Quite possibly. But I think that's the sort of the range. And I think in terms of the other compounds that have generated some data, I think that's kind of the range that they've been in as well. Can't speak to their programs. But I expect that we'll be in the market with our second indication NPM1 well ahead of others. So I think we'll be at the opportunity to really set the stage for others to follow, and it will be a high bar.

And then just obviously, for the investors on -- paying attention to your name, this would be Kura's Ziftomenib. They have been amongst the players who are long familiar in this environment, and I think competition always just makes everybody better. So from that standpoint, looking at the breadth of opportunity there, it's very helpful. You had already brought -- forementioned of opportunity to go more into frontline with combinations. Talk a little bit more about that because I think we have some potential data that could happen there as well.

We do. And we've actually presented some of that data last year at ASH. So we had 3 different presentations at ASH and an investor event and we laid out all of this combination data that was emerging. And I think the 2 highlights that will be presented at EHA in this coming week, abstracts are out. But presentations will update the data. One is the BEAT AML trial, which is testing newly diagnosed patients with a combination of ven/aza plus revumenib. And this is a very important standard of care, I'm sorry, revumenib plus the 2 other agents. And I think what we've seen thus far is 100% complete response, right? So the patients are doing really, really well in clearing their leukemia. We're seeing high rates of MRD negativity close to 100% of those patients go on to get an MRD-negative response. So these are deep, durable responses. I think at this upcoming EHA, you'll see additional patients, you'll see follow-up on duration. When we get a chance to really understand the profile in a larger segment of patients, which is fantastic. But this is the future of where we'll go. And this is, again, the unfit population, patients that are not generally getting transplants, but they're able to treat them until they progress to the next stage. And the idea here is can we add to standard of care ven/aza, which patients do pretty well. About 2/3 of patients get a response. We're showing closer to 100% response, and we're showing very high rates of MRD where the combination thus far, the doublet actually shows MRD in the 20% range. So we're really looking to change and add to the standard of care, of course, you want to do that without adding anything to the side effect profile, which we've been able to do. So this really looks like adding our drug to the doublet, doesn't do anything more in terms of safety profile. So that's fantastic. That's what physicians really want to be able to add this to that regimen. We're also -- at EHA, we'll update a cohort of AUGMENT-102, which is a chemo combination in relapsed/refractory patients. But that data is important because it starts to show how we can combine with chemotherapy and that data was put out at EHA last year -- or sorry, at ASH last year, and we'll update it this week. I mean week, but it's a very important regimen for how patients get treated in the frontline and also in relapsed/refractory. And then later in the year, we'll have a combination with ven/aza and -- sorry, not aza, but in Cobi, which is an oral hypomethylating agent. And that's an important regimen, all oral regimen, including ven, which we presented at ASH, we'll update that later in the year, and that's Ghayas Issa's trial at MD Anderson. Data there, again, even in relapsed/refractory patients, we're seeing a 100% response rate and with very high rates of MRD. So I think what we know today is that the drug is very combinable with standard of care ven/aza and other hypomethylating agents as well as chemotherapy. And we're not adding anything else to the side effect profile. So it's very tolerable, and it seems to be very effective. We'll see that in larger patient populations. But it's an exciting new area of how we're going to move the drug to earlier line settings which, of course, means that you can possibly treat more patients, you can keep them on drug longer and that's important for the overall franchise.

Absolutely. And when you think about the demographic of the patient range here, you want to make sure, very respective of what that therapeutic window could be looking like to be able to keep patients on the maintenance regimens. What are next steps here? Could you start a pivotal by year-end?

We expect to. Yes. So the expectation that we have is that we'll start a pivotal trial before the end of the year in the ven/aza combo we're doing, as I said, the work that we're doing will continue. We are getting to the point of getting our recommended Phase II dose nail down. So that will feed into the trial that we start in the fourth quarter. We are starting -- or we have started a 7 plus 3 Phase I, looking at the combination of our drug plus 7 plus 3 chemotherapy in the frontline setting. These are newly diagnosed patients in the fit population. So that work will continue. We'll get an RP2D there and ultimately start a pivotal trial, we think, in 2025. So that -- those are the important pillars on the frontline. And so in the not-too-distant future, we'll have 2 pivotal trials ongoing.

Okay. Great. And then Syndax was very gracious in making sure that you arrived at our conference with a new layer to talk about in terms of the portfolio advancements of solid tumors.

Yes.

Just at the end of last week, you talked about being able to make an advancement here in metastatic colorectal, outline for us what that update was. I think there were some specifics about dosing and just frame that opportunity?

Sure. Well, let's say it's a terrible disease as we know this is third line plus colorectal cancer. And in fact, the Phase I patients that we treated were more like fifth line. So these are heavily pretreated patients. Standard of care is suboptimal, I would say. And that's why you find yourself with 50,000-plus patients in this setting in the U.S. who are in need of new therapy. And it's very -- these patients are very hard to treat. And so what we're we were looking for as a signal in colorectal cancer monotherapy. So we tested 19 patients as of the update a couple of weeks ago or the last week. And essentially, we are tracking patients to see if we could have an impact either stable disease or better, and we've been able to show thus far, that there is stabilization of a number of patients looking out sort of land market at 4 months, 6 months, that time period because patients -- some patients respond to chemotherapy early but then relapse very quickly. And so our idea was well could we impact patients in that 4- to 6-month time frame, and then we showed some stable disease, which gave us some hope that we can potentially impact the disease, not only in monotherapy but perhaps down the line in combination, which is essentially what you'll do. So the IDMC said that we should continue this trial, we'll continue to look for signals. It's encouraging. I'd say, but it's early. It's quite early, and we'll know a little bit more as we go here. But that's our first foray into solid tumors as an expansion opportunity outside of what we're doing in AML and ALL.

Solid tumors that tends to get the heart rates to pulse a little bit faster and thinking about the expanded pipeline opportunities here and your ability to interrogate that very important. Let's talk about axatilimab please, graft versus host disease. Actually, the PDUFA is a little bit earlier end of August, right? So it could be a very happy Labor Day. Talk about this.

Sure. Yes. No, it's end of August under priority review. The data that we showed in third line plus graft versus host disease was best in category. Overall response rate is 74%. So these are patients who have been on treatment for an average of 4 years, and they're getting our therapy and they're still responding in such dramatic fashion. They're highly fibrotic patients. The mechanism of action here is both anti-fibrotic and anti-inflammatory which is first of its kind. The standard of care agents just deal mostly with the inflammatory component. So this is a new mechanism for patients and the data thus far has been fantastic, patients staying on therapy, more than half staying on therapy for more than 12 months. So again, I think this is a robust opportunity where we can bring a new agent with a new mechanism of action and really showcase how we can reverse in some cases, fibrosis, deep fibrotic patients have been able to do quite well. I think we showed across the spectrum, it's a multi-organ disease, right? So it affects multiple organs, some more difficult to treat than others, like lung and skin and we've shown sort of, I would say, best in category depth efficacy for those organs in particular, which has led to other expansion opportunities. Now we have a trial ongoing Phase II trial in IPF, which is a really important new test for the mechanism as well, and we're just getting going there. But we'll also now look to combine, as I mentioned earlier, combine our drug with standard of care agents, Jakafi and others perhaps steroids, 2 trials that will start before the end of this year to demonstrate how we can move it up line and really expand it for GVHD.

A little devil in the details, August 28, PDUFA, when we click through and think about the label dose. I think you've used the vocabulary approvable dose, 0.3 mg per kg. Would we expect to see something like that specific specifically on the potential label. Can you talk to that?

Sure. Yes, I think we would expect that to be the label dose. We've tested other doses in the pivotal trial both in other 1 milligram every 2 weeks as well as a 3-milligram every 4 weeks. And we did allow patients to move once they were stable at 6 months, to move to a more convenient dose not every 2 weeks, but every 4 weeks. So there are -- there's a fair amount of data that's been submitted to the agency. We'll see what -- where the label is. But essentially, I expect that we'll have some not only a 0.3 milligram dose, but we may have some other information in that label that allows physicians to titrate or do whatever they feel is necessary for their patients.

And then the commercial landscape includes REZUROCK as an existing competitor doing quite well, actually. And I think that actually is a reference point in terms of thinking about the scope of opportunity there. Share what you can about the plan of attack?

Yes, I can hit that. I think it's a market with a lot more in it. I think that's a well made point, Chris. I mean the -- I think the last numbers I saw with REZUROCK was maybe $100 million in the last quarter, annualizing at $400 million. There's some double dosing in there. So you need to take that into account for some portion of patients. But there's a ton of unmet need. And I think what we're seeing is with Jakafi's success, REZUROCK's success, patients are on for long periods of time on these agents. They'll use them alone, they'll use them in combination. So we're fortunate that we have Incyte as a partner. They know the space like no one else. When we talk about rev and trying to get ahead of things, obviously, we're building that. They have it all built, right? They know who we're calling on and when you think about a focused effort, it probably couldn't get any more focused. Transplant centers are -- I think there's 180 in the country, 35 makeup half of the patient volume. So you really can focus. And I think what the early work we've done on the market research side is there's a lot of excitement and interest about the profile.

And remind me, the pitch of how axa will be positioned relative to the STING therapeutic sequence combinations, substitution, new patients, what's the playbook?

Yes. I mean it will be 3 so the label is likely to read after 2 trials, steroids and C&I. So it will come somewhere after that. The trials had good data in them as we know. It will probably be used a little later initially, just like everything else is that it's new, but we do believe, based on the experience that we'll likely see a market. It will push itself earlier, especially as you do more work to support that.

And then, Keith, remind us in our models, how will the axatilimab sales hit the P&L?

Our partners at Incyte will be recording the revenue, the axatilimab revenue. It's a 50-50 to remind everybody, it's a 50-50 profit split. So the P&L that lives in the cloud will have net revenue, less COGS, less commercial expenses. We put our commercial expenses into that joint P&L in the cloud Incyte but there's a, call it, a net commercial profit, and we'll pick up half of that net commercial profit in our P&L. It will be called something like partnership revenue or collaboration revenue.

And then remind us and reassure us and investors in terms of where the balance sheet is at with all these objectives ahead, where are you? And where does that take you to?

Yes, sure. ended the first quarter with $522 million in cash. Guidance is that we expect that to be adequate to bring us through 2026. Again, as Steve said, it's a very focused, targeted commercial effort so modest investments there but adequate investments to be successful.

And that's what we know what we're planning. But obviously, Michael, you guys never sit still in fact, I think Anjali is not here because she's probably busy hunting down the next opportunity right? So we hope that she is being very productive on this day as well, but certainly, a lot to look forward a fascinating and unique and a high potential juncture for the company overall. Congratulations on the progress. Well, I did want to do a little bit of -- just a question for you, RTOR, real-time oncology review, let's kind of trash talk the FDA. Real time?

Real time. I mean they live up to the name. They've staffed the program. They're very serious about it. We're excited about it because it allows us to get -- allowed us to get going earlier in our submission and the review and it's real back and forth iteration, right? They query and we answer and they query, we answer really and really we'll know in the end if it was more efficient, but it certainly feels more efficient. It feels good.

Okay. That's validating. Perfect. All the best. Thank you. Thank you for joining us.

Thanks, Chris.

Thanks, Chris.

Thank you.

Thank you everyone for joining us today.