Welcome to day three of the Goldman Sachs Healthcare Conference. My name is Chris Shibutani, member of the Healthcare 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 of characters. I think the webcast tends to be only, you know, not video as well. So we're all sitting here in Miami in our bathing suits, but obviously we have Mike Metzger, the CEO, and some additional members of the team. Maybe Keith, I'll start with you. Just tell us a little bit about yourself.
Yeah, thanks, Chris. Thanks to Goldman Sachs for having us. Keith Goldan, Chief Financial Officer. Been with the company about two years now, and, yeah, turn it over to Steve.
Yeah, so happy to be here as well. Steve Kloster, Chief Commercial Officer at Syndax. I'm not quite at my three-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, 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 one asset. I think if people actually do the screening and the scope of that, it's unusual, and it's quite a milestone achievement. It's kind of like having twins. But, give us maybe for the base purposes of level setting, where you guys are at overall.
Right. Well, first of all, thank you, Chris. It is 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, appreciate that. Well, I would just say that 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 two first-in-class, best-in-class assets, one 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 sometime in the third quarter. Again, these are for patients who have a form of leukemia that's probably the worst prognosis in KMT2A, adults 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-
Yep.
in terms of a really important milestone beyond approval, and that is for NPM1. It's a second indication. So the setup here for a new company, commercial stage company, is that we'll have not only a first approval and a first mover advantage into that market and 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 two, so we have another molecule. It's axetilimab, 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, and we'll start those trials later this year. So in summary, we have these two first 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, you know, excited to be doing this.
Excellent. Let's talk a little bit about product profile, and obviously, that is generated from the data. AUGMENT trial, when we're talking about revumenib here, this is what is currently before the regulators, and is what's gonna 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 that have either AML or ALL, adult and pediatric patients. The data was, as I mentioned, first of its kind, very high rate of response rate in the mid-60s%. So roughly two-thirds of patients cleared the leukemia, which for this particular disease is very hard to treat. The endpoint of the trial was CR/CRh, a complete response or a complete response with partial hematological recovery, and we were at in the mid-20s%. And this compares, 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 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.
Mm-hmm.
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 a 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 and compassionate use. So we've been able to see this much longer duration of treatment and follow-up in the maintenance setting with patients in remission. It's a new paradigm for patients, where they've been able to treat these, this 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 to three 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-
Yeah.
That will compete with this, with this agent for any time in KMT2A. So it's a really good set up to start.
So obviously there's, you know, clinical management paradigms that can be quite precise, but we're talking about some real unmet needs and challenges that are there. So we're gonna get, we believe, in our house view, an 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 a satisfactory, maybe a potential, a 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, you know, Steve and his team, it's like, "Okay, go to market with this." Just frame that.
Well, maybe I'll let Steve address that, because he's the one who's gonna be working with it.
Yeah. Thank you. I mean, the label is, you know, ultimately the most important document we're gonna have. It'll form the basis for everything we say publicly. You know, 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... You know, we don't expect anything in the label from a class effect, black box and differentiation syndrome, that is gonna be any different. 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 of the label, which is the clinical trial section. It'll 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, 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 clinicians, 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, will guide clinicians on how to use the product successfully.
The math on any revenue forecast that investment community's been doing very much depends upon this notion of induction and maintenance, right? The extent, duration at which the drug is gonna be used. Talk about how you see the potential implications of label, and here's where the practice of medicine actually gets invoked more often, in thinking about how 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, 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?
Yeah, I can take a stab at that one. I think that is the goal of treatment, and mind you, my time here is limited, three months in the role. But, you know, 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 gonna use post-transplant. Some of it's anecdotal. You know, 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 gonna have to play out in real time, but that is the instinct of physicians to do it, and we think that'll 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.
Maybe I'll just amplify that a little bit. I think the additional data that's being generated is also very important to the practice of medicine, such as, newly diagnosed patients using it in combination with venetoclax, which is-
Right
... 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, in more spontaneous ways. So I think it's. These are, you know, 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, you know, KMT2A and NPM1 itself.
Yep.
And modify-
Here again, there's a lot of building blocks, the size and 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.
Yeah, happy to do that. I think, you know, often we look back to analogs and how successful have predecessors or similar products in the space been, and I think if some of those products were, you know, introduced to market now, there'd be a higher pricing power to help them, and I think, you know, you need a type of population that you can extend treatment on. And I think we have both, you know, really in the menin space, particularly for revumenib. So I think, you know, from a numbers standpoint, in total, KMT2AR and NPM1, you've got about 6,000 patients that are relapsing and refractory. Obviously, the frontline is gonna be maybe 1.5 times that.
But if you do some simple math, you look at a pricing card of, we'll say, $30,000-$40,000 a month, a duration of treatment somewhere between 6 and 12, you know, that initial opportunity is about $2 billion, roughly, for the compound. I think what makes it unique for revumenib, in addition to a, 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, we've done our 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 we talk about first mover advantage, you really, you know, you 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. You know, modest size sales team, promotional effort, which is unique because my experience is often in larger categories where there's a little bit of an arms race. The more reps, the more money spent, the more you drive success.
I think this is a space where companies, small, medium, and large size, can all compete because there is a point of diminishing returns. But our plans, really for launch, are to fully staff our teams, engage, you know, 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 that may or may not come later in, in the life cycle of the compound.
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... But it's in CNS infectious disease, which is a smaller space, not quite as small, I think-
Mm-hmm
... as, as this, but hospital-based, infectious disease, drugs with a lot of science, unique distribution systems, buy and bill-
Mm-hmm
things like that.
Right. And how's your arm wrestling with Keith going as far as getting enough resources and, and checks for him to write to, to equip your success?
Yeah, I think, I mean, that's funny. But I think, you know, 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.
Mm-hmm.
So I feel very comfortable, 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 wanna 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 gonna have from 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, 30-50 range. You know, somewhere in there, which I think is consistent with other agents that have been on the market. But, I will, I will say this: I mean, the market is complex for patients. You know, 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 you know, we've, we've aligned on a model that has a, a few different customer-facing roles-
Mm-hmm
... that's able to really interface-
Mm-hmm
... completely, because that's what we think will lead to better success. We are fully staffed. I mean, really, since I've been here, it's a, it's a plan for success. You know, we, we have full faith in, in, in really both products. Getting through FDA, we're, we're very, optimistic. So we're fully staffed, so our entire sales team, is on the ground. We, 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, you know, in this space and you're in sales and that- that's your job, Syndax has been on the radar for many, many folks.
Mm-hmm.
So this is gonna sound like a college entrance statistic, but, you know, we posted these roles back in February, we'll say between 30 and 50, we had 4,500 applicants that applied. So, you know, 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 six or seven startups, 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.
Mm-hmm.
And they'll know who's who, what's their... How do they test patients for, you know, rearrangements or other mutations? So at the time of launch, we, you know, we're not walking, we're almost running with the opportunity to make sure that the drug gets to as, 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 of at the respective sites that you're at, there's kind of two subspecies, right? The hematology oncology crowd, as well as the transplant physicians. And oftentimes, it's kind of, you know, reaching out to two sides of the beast, so to speak.
Sure.
They need to typically work in some collaboration. There's some tension points about decisions, which are typically made by disease management committees, but it's gonna 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 gonna 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 axetilimab , so that there's a thematic and market logic to what you have there, right?
Yeah, I'm gonna let you comment 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, you know, they're leukemia specialists, but the subset of that specialty is the transplant physician. 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 and a dynamic one at the same time, bringing two products to bear, not one, but two 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, you know, two 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.
Mm-hmm.
I mean, I think because the you know the headcount we're talking about, it's really small, honestly, in this space. So, you know, we're sizing for the NPM1 opportunity, we're sizing for axetilimab at the launch. And that was a conscious decision.
Mm-hmm.
I think that's one where you, you know, you feel great about your products, you feel great about the, you know, the chance of regulatory success. You know enough about the market-
Mm-hmm.
What are the different levers?
Mm-hmm.
Anytime you expand, restructure, you're just causing distraction.
Mm-hmm.
You know, we frankly need a customer-facing team that has no distraction, that just has our unwavering support, put the right, you know, support in place, let them do what they do, which is, you know, customer engagement, really at the end, supporting patient success. So that's...
Mm-hmm.
That was a good, good point you made.
Yeah. 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 gonna be a fun ASH, as it always is, but especially with you guys out there on the market.
Yeah.
Now, investors that are very specialists, focused on data, the upcoming NPM1. Let's frame that opportunity here.
Sure.
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 was in 14 patients at the RP2D. We had... I would characterize our data as best-in-category data for NPM1 patients. This is in AML only. A 36% response rate, CR/CRh, 50% overall response rate, 100% of the patients who had CR 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, you know, 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-
Mm-hmm.
is pretty, it's pretty noteworthy. So I would also say that the data that we've seen with KMT2A and NPM1 are very similar, right?
Mm-hmm.
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 in a maintenance capacity. We've had patients continue as NPM1 patients on therapy in that trial, the phase I. And so we expect the data to be actually quite similar to what we've seen in NPM1, which was very good. 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-
Mm-hmm
... to undergo transplantation. But, we've seen, you know, great, great safety tolerability as well as efficacy in that population, so we expect the data to be, you know, 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.
Yeah.
We have a backdrop about standard of care, and there's a competitive environment as well.
Yeah
-with other companies with assets there. Frame that dimension and what we should expect on that CR rate and durability in comparison.
Sure. Well, I think we've established that, you know, 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 three years plus in both of the trials and outside of the trials themselves in compassionate use settings. 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%-30% CR/CRh rate is sort of the range of what we would possibly expect, and, and all... Based on prior data, and I would say a durability in a four- to six-month range is certainly this is all, you know, approvable, if you will. And that's, you know, 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 on the market, with our second indication, NPM1, ahead, well ahead of others. So I think we'll be at the opportunity to really set the stage for others to follow, and it'll be a high bar.
And then just obviously for the investors 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 forth mention of opportunity to go more into frontline with combinations.
Yeah.
Let's 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 three different abstracts or presentations at ASH, and an investor event, and we laid out all of this combination data that was emerging. And I think the one, two to highlight that'll 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 venetoclax plus revumenib, and this is a very important standard of care, aza, I'm sorry, revumenib plus the two other agents. And I think what we've seen thus far is 100%, you know, complete response, right?
Mm-hmm.
So the patients are doing really, really well in clearing their leukemia. We're seeing, you know, high rates of MRD negativity, close to 100%. So 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-
Mm-hmm
... 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.
Mmh.
They're able to treat them until they progress to the next stage. The idea here is, can we add to standard of care venetoclax, which patients do pretty well?
Mm.
About two-thirds of patients get a response. We're showing closer to a 100% response.
Mm-hmm.
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.
Sure.
So this really looks like adding our drug to the to the doublet, doesn't do anything more on, in terms of, 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-
Mm-hmm
... in relapse refractory patients. But that data is important because it starts to show how we can combine with chemotherapy. That data was put out at ASH last year, and we'll update it this week. I mean, but it's a very important regimen for how patients get treated in the front line and also in relapse refractory. And then later in the year, we'll have a combination with venetoclax and Inqovi, 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 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 venetoclax-
Mm-hmm
... 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 seems to be very effective. We'll see that in larger patient populations, but it's an exciting new area of how we're gonna move the drug to earlier line settings, which, of course, means that you can possibly treat more patients.
Mm-hmm.
You can keep them on drug longer, and that's important for the overall franchise ability.
Absolutely. I mean, you think about the demographic of the patient range here, you wanna make sure very respectful of what that therapeutic window could be looking like-
Right
... 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 venetoclax 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 nailed down, so that will feed into the trial that we start in the fourth quarter. We are starting, or we have started, a 7+3 phase I, looking at the combination of our drug plus 7+3 chemotherapy in the front line 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 those are the two important pillars on the front line, and so in the not too distant future, we'll have two 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.
Yeah
... you talked about, being able to make an advancement here in MSS colorectal.
We did.
Outline for us what that update was. I think there were some specifics about dosing and just frame that opportunity.
Sure. Well, 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+ 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 is a signal in colorectal cancer monotherapy. So we tested 19 patients as of the update a couple weeks ago or the last week. And essentially, we were tracking patients to see if we could have an impact, either stable disease or better.
We've been able to show thus far that there is stabilization of a number of patients looking, sort of, landmark at 4 months, 6 months, that time period, because some patients respond to chemotherapy early, but then relapse very quickly. So our idea was, well, could we impact patients in that 4-6month timeframe? And we showed some stable disease, which gave us some hope that we can potentially impact the disease, not only as 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.
It's 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 axetilimab, please. Graft-versus-host disease. Actually, the PDUFA is a little bit earlier, end of August, right? So could be a very happy Labor Day. Talk about this.
Sure. Yeah, 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, 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. Standard of care agents just deal mostly with the inflammatory component. So this is a new mechanism for patients, and the data thus far, you know, 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, deep fibrotic patients have been able to do quite well. I think we showed across the spectrum; it's a multi-organ disease, right?
Mm-hmm.
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, a phase 2 trial in IPF, which is-
Mm-hmm
... 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-
Mm-hmm
... and steroids. Two trials that will start before the end of this year to demonstrate how we can move it upline and really expand it for, for GVHD.
A little devil in the details. August twenty-eighth, PDUFA, when we click through and think about the label dose, I think you've used-
Yeah
... the vocabulary. Approvable dose, 0.3 mgs per kg.
Yeah.
Would we expect to see something like that specifically on the potential label? Can you talk to that?
Sure, yeah. I think we would expect that to be the label dose. We've tested other doses in the pivotal trial, both another 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, move to a more convenient dose, but not every 2 weeks, but every 4 weeks. So there is 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.
Then the commercial landscape includes Rezurock as an existing competitor, doing quite well, actually. And I think that actually is a positive reference point in terms of thinking about the scope of opportunity there. Share what you can about the plan of attack.
Yeah, I can hit that. I think, you know, to market with a lot more in it, I think that's a well-made point, Chris. I mean, the, I think last numbers I saw was Rezurock was maybe $100 million in the last quarter, annualizing at $400 million.
Mm-hmm.
There, 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, you know, patients are on for long periods of time on these agents. They'll use them alone, they'll use them in, in combination. So, you know, we're fortunate that we have Incyte as a partner. They know the space like no one else. You know, when we talk about rev and trying to get ahead of things, you know, obviously, we're building that. They, they have it all built, right? They know who we're calling on, and, and when you think about a, a focused effort, it probably couldn't get any more focused. Transplant centers are...
I think there's 180 in the country, 35 make up half of the patient volume, so you really can focus. 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.
Remind me, the pitch of how axetilimab will be positioned relative to the existing therapeutics. Sequence, combinations, substitution, new patients, what's the playbook?
Yeah, I mean, it'll be 3L, so the label's likely to read after 2 trials, you know, steroids and, and CNI.
Right.
So it'll come somewhere after that. You know, the trials had good data in them, as we know. It'll probably be used a little later initially, just like everything else that is new. But, you know, we do believe, based on the experience, that we'll likely see in market it'll push itself earlier, especially as you do more work to support that.
And then, Keith, remind us, in our models, how will the axetilimab sales hit the P&L?
Our partners at Incyte will be recording the revenue. The axetilimab 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 puts theirs. There's, call it, a net commercial profit, and we'll pick up half of that net commercial profit in our P&L. It'll be called something like partnership revenue or collaboration revenue.
Then remind us, the issue for us and investors, in terms of where the balance sheet is at with all these objectives ahead-
Sure.
Where are you, and where does that take you to?
Yeah, 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, you know, modest investments there, but adequate investments to be successful.
That's what we know and 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.
Exactly.
Yeah, right.
Mm-hmm.
So, we hope that she's 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.
Thank you.
Oh, I did wanna do a little bit of a, just a question for you. RTOR, Real-Time Oncology Review.
Yeah.
Let's kind of trash talk the FDA. Real time?
Real time. Real time. I mean, they, they, they live up to the name. They've staffed the program. They're very serious about it. We're excited about it because it allowed us to get going earlier-
Mmh
... in our submission in the review, and it's real back-and-forth iteration, right? So they query, and we answer, and they query, and we answer, and it really... We'll know in the end, if it was more efficient, but it certainly feels more efficient. Feels good.
Okay, that's validating. Perfect. All the best. Thank you-
Thank you
Thankyou... all of you for joining us.
Thanks, Chris.
Thank you, everybody, for joining us today.
Thank you.