All right, let's get started. Ben Burnett here, Biotech Analyst at Stifel. Pleased to be joined by, Jonathan Yu, Chief Business Officer of Disc Medicine. Jonathan, thank you for being here.
Thanks, Ben.
You know, I think a lot of people are familiar with the story, but maybe it would help if you just kind of give a quick overview and kind of talk about some of the near-term catalysts. I know we're imminently approaching ASH, so-
Yeah, exactly. Yeah, thanks for having us today. So just a quick overview about Disc. As the name implies, and that frankly, our, our ticker symbol as well, Disc Medicine is a company that's focused on developing therapies to treat hematologic diseases. The way we've went on about doing that is building a portfolio of agents that control what we call fundamental pathways of red blood cell biology. And in short, we have programs that control how heme is synthesized and also controls iron homeostasis. So key components of hemoglobin, which is fundamental to a red blood cell, we control the vertical, we control the horizontal, and that gives us a great platform to be able to enter a wider range of diseases, anything from severe rare hematologic disorders to widely prevalent chronic diseases of like anemia. So we currently have three programs in development.
Our lead program is a drug called bitopertin. It controls heme synthesis. That's in phase II studies right now for a rare disease called erythropoietic protoporphyria. So that's our heme synthesis program, and we have two iron control programs, one called DISC-0974, that's designed to increase iron levels by suppressing a hormone called hepcidin. That's in two phase I-B/II studies, one in MF anemia and one in CKD anemia. And we have a last program that we just initiated a phase I trial for, that also controls hepcidin, but in the opposite direction. So that's designed to restrict iron, by increasing hepcidin. So we just started a phase I study of that in healthy volunteers, so proof of mechanism data to come.
Okay, that's fantastic. So I think, we just had some updated data in an ASH abstract with regards to the bitopertin program.
Right.
The others were also showcased, but talk about those data and what's incremental that we'll learn at ASH?
Yeah. So at EHA this year, we released data on our lead program, bitopertin in EPP, that was pretty—we felt pretty compelling proof of concept data, showing that our drug is able to reduce the key metabolite, PPIX, in EPP patients, and also that it was able to have a pretty profound impact on photosensitivity, which is the primary issue that these patients deal with. Now, that was in just, you know, that was just in a handful of patients, only two patients of which had received full course of treatment, six months of treatment. So what we can expect at ASH is kind of building on that. We will have—we've guided that we will have data from 22 patients, at least 15 of which have been on the drug for six months.
So folks will get a better feel for the same kind of data that we saw at EHA, but we'll have a better feel for, you know, what does the activity look like in a larger number of patients and in patients who've been treated for a longer period of time. I think more importantly, this will also be the first analysis we have of the precedented pivotal endpoint. So this is a fairly convoluted endpoint called, you know, that is cumulative time spent in light on days without pain. But we should have enough patients that we that have been on the drug long enough that we can get a first look at that as well.
Okay, that's great. And of course, if there's any questions, jump in. I wanna obviously talk about this program and the clinical data that you generated at EHA and showcasing the abstract, but I do wanna talk about the commercial opportunity first and just kind of the number of patients that are out there. Like, can you frame for us, like, what the addressable patient population that you're seeing as potential in the US?
That's right. So we've been doing a lot of work on understanding the addressable patient population. We'll be sharing some of this data at ASH in a corporate meeting there. But briefly, we've been saying that there are 7-8 thousand patients in the U.S. and Europe. And to be clear, these are 7-8 thousand addressable patients, and that they're symptomatic, they've been diagnosed, and that they're seeking treatment in the healthcare system. The only issue is that there is no treatment for EPP. And I think one of the things that distinguishes EPP from some other orphan diseases is that there's already an ICD-10 code.
So when you go into the claims data, when you start doing some of your patient identification work, you're able to know how many patients are there, you know where they are, you know how intensively they're seeking treatment in the healthcare system. So we feel very good about these 7,000-8,000 patients being addressable. But we've also, in addition, as we've done some more work, realized that there's an opportunity for this to grow with the drug and, and for it to improve diagnosis rates. The genetic prevalence would predict that there are at least 20,000 patients in the U.S. that have this disease, but for whatever reason, they may be misdiagnosed or under-diagnosed or taken themselves out of the healthcare system.
So 7,000-8,000, which is a good core group of patients off of which to build a business, but room to grow from there.
Okay. So the diagnosis rate that we should think about is something like that, 7,000-8,000 patients based off relative to the genetically-
Yeah
the applicable population.
40-50 thousand in U.S. and Europe, based on-
U.S. and Europe.
Yeah.
Okay. Okay, excellent. And then talk about the competitive landscape. So Scenesse is out there. It's a little bit of a different MOA, but talk about that asset and kind of the data that they have and I guess, how does that-
Yeah
make you think about bitopertin?
So there's only one agent that's approved for the treatment of EPP. It's a drug called afamelanotide or Scenesse. It's a tanning agent, and it was launched in 2020. Its efficacy is limited. It's palpable, but limited. And the way it works is, you know, these patients, they experience excruciating pain when they go in the sunlight. The concept here is this stimulates melanin production, that provides a little bit of opacity, and that gives you some protection from the sunlight. It is not disease-modifying, and its use has been pretty limited. It's a very cumbersome presentation. It requires a surgical procedure once every two months. And its availability has been highly restricted. So its availability and its uptake has been very, very, very, very small. And that's it.
You know, there's one other agent that was in development. It was in phase III. It's an oral tanning agent. Its efficacy seems also approximating what these tanning agents are. It was being developed by Mitsubishi Tanabe, a drug called dersimelagon. You know, we recently learned that the drug won't be available till after 2025. They finished a phase III trial almost 15 months ago, and at a recent porphyria conference, we learned that they missed their primary endpoint. And beyond that, their efficacy endpoint. And beyond that, there's nothing else in clinical development. So it's, it's a pretty, it's a pretty high unmet need population. The disease is unrelenting. The patients are constantly reminded of it, and there's, you know, really no you know, no highly effective treatments out there. So, we think that we provide something that patients will very much need.
Yeah. You know, I, and one of the differences, I think, between bitopertin, you mentioned that Scenesse is not disease-modifying, but bitopertin has shown an effect on, on a biomarker, PPIX, which is, I think, relevant to the genetics. Maybe, maybe talk about that, and, and maybe talk about also the link, like, what's how, how strong is the link between that biomarker and some of these, like, clinical endpoints-
Yeah
... sunlight tolerance?
Sure. Yeah, so EPP is a disease of mutations of the heme synthesis pathway. It affects an enzyme called ferrochelatase, which is the last step in forming heme synthesis. These patients have a loss-of-function mutation in ferrochelatase, and that causes the accumulation of this metabolite called PPIX. And PPIX is what drives all of the disease pathophysiology in EPP. It is a toxic and photoactive metabolite. It gets produced in high quantities in the red blood cell. It gets distributed in the body, and it collects in end tissue organs, the skin, and the biliary tract. One of the things about PPIX is it's photoactive, so the moment that visible light shines on it, it causes it to absorb light and then radiate energy, and that's what causes the excruciating pain.
So this biomarker actually is also what causes the disease, and that's important to us because then, you know, to your question, it's highly correlated to, to the disease pathophysiology. We know that patients who have higher levels of PPIX tend to have worse disease severity. There have actually been examples in that have shown that if you can intervene at and lower PPIX, you get improvement in light sensitivity. So there's a very interesting phenomenon in patients with EPP. When they become pregnant, their PPIX levels drop by about 30% or 40%, and during that time, when their PPIX levels are low and while they're pregnant, their disease essentially disappears. And that was quite interesting to us 'cause it shows that when PPIX levels drop, you no longer have any evidence of the disease.
Now we have interventional data that we showed at EHA, showing that when we drop the PPIX levels, we got very profound improvements in light tolerance.
Absolutely. You know, it's also interesting with some of these studies, we've seen baseline PPIX kind of be different for different patients, sometimes by a lot. So is it like what does it make sense, therefore, to look at this on a percentage reduction? And if so, is there like kind of a threshold that you'd look for as-
Yeah, it's a very common question that we get. I think what we've seen from the literature seems to be a relative reduction in PPIX. Now, if one looked super close, maybe there is a threshold, but our sense is if you can drop PPIX levels by about 30%-40%, you're able to get that profound magnitude of benefit. You know, this has been shown in the example of pregnancy I was discussing earlier. But there was actually another example, done by a Danish group, where they took patients' blood, they were able to extract it, shine it on UV light, that deactivated PPIX, reinfuse that blood into the patients. That dropped PPIX levels by about 30% or 40% as well, and they also showed this profound improvement.
So it seems to be a relative reduction.
Yep. Yep. Okay. You know, I think there's also some discussion around the potential for this to cause anemia, and I think historically, as I understand it, there was an anemia signal when this was in Roche's hands, and that's what kind of, like, alluded to this potential mechanism. EPP is different. Maybe talk about why you don't expect anemia, and then-
Yeah
thoughts on that.
Exactly. So very fair question. In fact, this is how we knew that bitopertin was a heme synthesis modulator, in that in hematologically normal patients, you saw a pretty regular 1-2-gram drop in hemoglobin. And it wasn't, it didn't continue to drop. It, you know, 1-2-gram hemoglobin drop, and then it sort of plateaued out. The key difference between healthy volunteers or healthy hematologically normal patients and EPP patients is that, hematologically normal patients have undetectable levels of PPIX. There is no accumulation because that enzyme, ferrochelatase, is extremely efficient. In the case of EPP patients, you have massive accumulations of PPIX.
That's what causes the disease, but, you know, if you look at the red blood cell of an EPP patient, you have hemoglobin, but it also comes at the cost of, you know, coming along with the high levels of PPIX as well. So when we think about treating these patients, you're able to bring down this high reservoir of PPIX level, level of PPIX, without impacting heme synthesis. You still have an excess of PPIX. Fundamentally, that's why we don't think that it'll affect hemoglobin. We've modeled this in silico, we've done cell studies, we've done animal studies, and now and what we showed at EHA, that across all of these, the thesis proves true, in that you can reduce PPIX levels to pretty, pretty significant levels without impacting hemoglobin.
I think that's maybe one thing that folks will be looking for at the data update at ASH. Now, we have more patients who've been on the drug for a longer period of time, and so we'll be... You know, in addition to the usual safety data, data we'll be showing, we'll be also showing hemoglobin data.
Great. Okay. So just to kind of dig into this, so in EPP patients, the genetic mutations that they tend to have are some defect in the ferrochelatase enzyme, therefore, you have an inability to normally move PPIX and convert it to heme, build up PPIX in those patients. So I guess the question is, if you continue to dose bitopertin chronically? Like, why wouldn't that take PPIX all the way down to zero eventually, and kind of make sort of a heme normal-
Yeah-
-condition?
... I think mechanistically, you know, the way that the drug works, it inhibits the transport of glycine, so it limits the amount of glycine that's coming in. So by restricting some of this, I guess, the starting materials to create heme. But there are other ways you can get glycine as well, through diffusion, et cetera. And I think maybe the best evidence really is that Roche, when they were developing bitopertin, they treated patients with bitopertin and followed them for years. And pretty consistently, you saw anytime there was a drop in hemoglobin, it occurred within the first few months and then stabilized. So it always reached a plateau. And so there's no reason to think that that wouldn't be the case in EPP as well.
Cool.
Yep.
Okay. Okay. And so, we're getting data for BEACON at ASH. You also have another study, a company-sponsored study, AURORA. Maybe talk about the differences. Are there any differences in kind of like the endpoints, how these studies are adjudicated?
Right. So we have the BEACON study, which is an open-label study, that's being conducted in Australia. At the same time, we have the AURORA study. The primary difference is really twofold. One, it's, well, it's threefold, I guess. It is being conducted in the U.S., 75 patients instead of 22, and instead of six months of treatment, four months of treatment. And it's double-blind, placebo-controlled. This just helps us get a better feel for understanding the endpoints and working with... And having a placebo arm, so we can understand how these endpoints perform in a placebo, in a placebo setting. Other than that, the studies are essentially the same.
Which is adjudicating the endpoint, that's all.
Exactly.
Yeah.
Yeah, we'll be looking at PPIX, we'll be looking at photosensitivity, we'll also be looking at the time and light.
Okay. Just based on the literature, is there any expectation that EPP patients are different in different geographies?
There doesn't seem to be. You know, there's Mitsubishi Tanabe. They published their phase II results from dersimelagon, from the drug dersimelagon. This is the oral tanning agent. They did a retrospective analysis looking at geography and also seasonality, and it appears that it doesn't really have an effect on at least these endpoints that you, they look at. I think intuitively, it makes sense to us because a patient, whether it's fall, winter, or no matter where you live, they continue, they will have the same photosensitivity issues. You can still trigger an attack, even on a rainy day, so, or cloudy day, so.
Yep. Okay, okay. Maybe circling back to kind of the competitive landscape, and we talked about Scenesse and dersimelagon, but, but given those assets that are out there, or really just Scenesse, what, what kind of efficacy profile would you view as sort of competitive, from AURORA?
Yeah. I mean, I think if we look at the efficacy of Scenesse and I guess the tanning agents, you know, I think I would call the benefit is palpable but limited. I think the benefit that you've seen is order of magnitude around a 50% improvement, which is fundamentally different than what we saw, you know, what you see with these examples I cited, where patients, you know, drop their PPIX levels, they get, like, transformative kind of light sensitivity benefits. And our EHA data showed that you had, like, order of magnitude improvement of light sensitivity. Still, you know, that was initial data, but that told us that, you know, you're probably operating a different level of efficacy and potential benefit to patients.
So I would say the bar is fairly low, I think largely because there is no treatment out there, and even to give patients just a little bit more time and light, that could be meaningful. But I think the potential, the potential profile that we could potentially deliver could be transformative. And this doesn't include the fact that, you know, we have an oral presentation and that we're also reducing PPIX levels. Because remember, accumulation of PPIX over a lifetime also results in these biliary complications, which the tanning agents won't affect at all.
Yep. Okay, that's great. And I guess, actually, one last question, kind of going back to the safety piece. There's a little bit of signal of dizziness in the EHA data set. Any, any color you can provide around that?
Yeah, I mean, the safety profile is extremely well understood, given the large data package that Roche had generated. And so the things that we had talked about in our EHA presentation, dizziness, somnolence, I think headache, these are all consistent with what was reported with the Roche in the Roche data package. The short answer is that all of those AEs that were reported were grade one and transient. So within a matter of one to two days, you know, they sort of... The patients stayed on the drug, but they sort of disappeared, so.
That's great.
Yeah.
Okay. Okay, so let's move on then to DISC-0974. I want to start with... You have a couple of programs. I want to start with myelofibrosis. Maybe just talk about the mechanistic rationale for targeting hemojuvelin in myelofibrosis.
Yeah. Yeah, so myelofibrosis, so, you know, it's this precancerous condition, affects about 20,000 patients in the U.S., but, you know, a hallmark of the disease is severe anemia. Almost all of these patients have severe anemia. Most of them end, almost all of them end up on transfusion, the vast majority are on transfusions. It's very difficult, the anemia has been very difficult to treat. You know, EPO, danazol, they all have very, like, marginal benefits. I think one thing that makes it, MF, quite interesting is all these patients have extremely high levels of hepcidin. And what this hepcidin does is it restricts the availability of iron. So all these patients have a profound iron blockade, and our goal here is to be able to reduce hepcidin, release iron, and that enables patients to be able to produce red blood cells.
And there are good examples now, largely from a drug called momelotinib, that was originally being developed by Sierra Oncology and has now been approved by GSK, that does reduce hepcidin by about 50%, and that was able to show a fairly significant, substantial, consistent effect on anemia. So our perspective is, if you take our agent 974, if you can profoundly suppress hepcidin, you can add this onto whatever backbone of treatment you have for MF patients. Specifically, our target, the target being our ability to be able to add it on to enter the first line setting by adding it on to ruxolitinib, which is the current standard of care.
Okay, that's great. You know, I think mechanistically, you mentioned momelotinib, so I think momelotinib, part of its, its binding repertoire includes ALK2, which I think sometimes they refer to as ACVR1.
Correct.
So ALK2, you know, I think there's mechanistic overlap with, with hemojuvelin. So I guess, I guess what are the expectations for differentiation with, with ALK2 inhibitors?
Yeah
... in this category?
So we were very deliberate in choosing hemojuvelin as a target. So hemojuvelin, ALK2, various BMP ligands, they all form a signaling complex that drives the expression of hepcidin or the HAMP gene. The problem with each of these other components of the signaling pathway is, they're implicated in multiple other tissue types. And so, for example, ALK2, it's embryonic lethal. If you knock out ALK2, we know it's, for instance, expressed in the bone. We know that if you knock out ALK2, it's embryonic lethal. HJV, on the other hand, is if you knock it out, the only phenotype you get is an iron dysregulation. It's kind of what we're looking for, hepcidin suppression and potentiation of iron.
In fact, there are patients who have loss-of-function mutations in hemojuvelin that develop a condition called juvenile hemochromatosis, and that is their only phenotype: lower hepcidin, higher iron. So what that allowed us, that gave us confidence in hemojuvelin as a target in that it would give us the necessary therapeutic index. If we needed to, if we needed to drive up antagonism of hemojuvelin, we felt we had plenty of room to be able to do that, to be able to suppress hepcidin sufficiently and to drive up and to improve iron levels to whatever degree you need to.
Okay, excellent. So I think we've seen a little bit of data from Incyte's ALK2. Keros has an ALK2. So I guess with your view of the landscape and kind of the feedback you're getting from myelofibrosis KOLs, what's sort of the efficacy profile you would ultimately want to see from something to be competitive?
Yeah, yeah. I think that, you know, the good news is that you don't really need to see very much. I think what you need to see is something fairly consistent, and what KOLs are looking for is: we wanna be able to see reduction in transfusion burden. We wanna see meaningful hemoglobin improvement. Order of magnitude, that looks like about 1-2 grams improvement of hemoglobin. And then I think what's most important is additivity onto backbone therapy. So where the field right now is going is you have any number of various treatments that are being developed that do a pretty good job now of controlling symptom burden and spleen size. But what's sort of left open is anemia.
So if you can optimize those things, and if you can have a product that is able to also address anemia, and frankly, allow you to be able to optimize dosing of some of these backbone agents, that would be a, that would be a killer combination.
Yeah. Okay, excellent. I think you mentioned, you know, some of these patients are in the front line on ruxolitinib, Jakafi. Many of them are on low-dose ruxolitinib. Do you have a sense for how many patients that are out there on low-dose Jakafi?
Uh-
Is that the right way to maybe think about sort of an early adopter market opportunity?
Yeah. It isn't really how we... I think that's one component of how we-
Okay
... think about the market. But I think the way we think about it is, when a patient is treated with ruxolitinib, you start off—you should start off being at about 10 mg BID. 5 mg BID basically is ineffective. But every patient who ends up on ruxolitinib usually ends up also being anemic. So we think about it as whatever dose you're on with... If you're on ruxolitinib, whether it's 5 or 10 or 15 or 20, you should also have an anemia agent that's helping you address the anemia because that'll either help you maintain your treatment with ruxolitinib, but allow you to dose escalate if you need to go—if you need to be at a higher dose.
If you are at the 5 mg BID, you should really be at the 10 mg BID at least with our drug on top of that. It's really any patient on rux, you know, and if you're anemic, which is the vast majority of patients, adding our drug on top of that would offer a benefit.
Okay, excellent. And can you frame what we should expect at ASH in terms of this program?
Yeah. So we are in a phase I-B/II study right now of anemia and MF. We're still. We have guided that we'll be sharing the first data from the phase I-B portion of the study. We are still dose escalating, but we'll be sharing about 10-20 patients' worth of data. The early dose cohorts will be sharing data on hepcidin, iron, and hemoglobin.
Okay.
Folks will have a sense of, you know, are we engaging the mechanism?
That's great. Okay, fantastic. And maybe, let's move now to, so the same asset, DISC-0974, and anemia associated with chronic kidney disease. Is kind of the underlying biology, is it sort of the same MOA that's being tackled here?
Slightly. So yeah, again, in CKD patients, you have extremely high levels of hepcidin. What's driving this is similar to MF, it's a highly inflammatory. You have any number of inflammatory underlying conditions that induce production of hepcidin. So that's a similarity to myelofibrosis. You know, MF is a highly inflammatory disease. There are underlying inflammatory diseases in CKD as well that drive hepcidin production. But the other component about CKD is that hepcidin is typically cleared by the kidney, so but as you lose kidney function, you have this accumulation of hepcidin as well. So what happens in CKD patients is all of them have, again, an iron blockade issue. What's more, you know, prominent is EPO and loss of EPO function, but parallel to that is an iron problem. And there just hasn't been an effective hepcidin control agent up till now, so.
What is like iron supplementation work?
It does work pretty well, except, you know, the caveat being IV iron. So parenteral iron, all sorts of issues with adherence, absorption, largely doesn't really work particularly well. Most patients are offered it, most patients end up, you know, not liking it. There are good precedents in the CKD anemia setting, where IV iron is able to get, you get about a gram of hemoglobin increase, within a matter of weeks.
Cool.
So-
Okay.
There's clearly an iron issue in CKD anemia.
Yep. Okay. And you're focusing on non-dialysis dependent. Why that segment?
Yeah, I mean, this isn't to say that hepcidin doesn't have a role in the dialysis setting, but in the non-dialysis setting, there are all kinds of reasons, some of them being commercial. It is a massive, massive proportion of the patients. So we estimate there are about 5 million-6 million anemia patients, CKD anemia patients. 500,000 of those are dialysis dependent. There are about 5 million patients with non-dialysis dependent CKD anemia, and all these patients are essentially untreated currently because there is no effective, convenient, outpatient, anemia treatment for NDD patients. In a dialysis setting, these patients are in the healthcare system already. They're going to the dialysis center three times a week. They're heavily treated with ESAs and IV iron.
The last thing is in the NDD setting, from a reimbursement perspective, there's just you don't have to worry about the complexity of the bundle. It's just much more straightforward. So our agent, having something that's not an ESA, that is going to be subQ, very low volume, amenable to outpatient treatment, I think that's sort of why we chose it as our core initial indication.
Yep. Awesome. Okay, that makes sense. And I, I wanna ask also, so do you have any expectation for kinda like what would be a, an active dose in this population based off sort of the healthy, healthy volunteer data?
Yeah, I mean, we don't know right now because these patients do have elevated hepcidin, and I think that's one of the exciting things that are coming out of the I-B/II study. But we know from the healthy volunteer study, and these patients aren't anemic, but at the 56 mg dose, a single dose, a single dose of DISC-0974 resulted in, you know, profound hepcidin suppression, increased iron availability, and we got a 1 gram increase in hemoglobin relative to placebo that lasted out to 70 days. So what that tells us is, okay, around 56 mg, you're in a sort of active range where you can detect a change in hemoglobin.
You know, we have the opportunity to dose escalate in our I-B/II study, but that gives you sort of a feeling of, you know, where you can start triangulating the dose.
Okay.
So, we will be presenting data from the I-B portion of the CKD study, just the first cohort, that's a 28 mg cohort, and we'll be showing hepcidin iron data. But, you know, we didn't see hemoglobin change at the 28 mg dose level in the healthy volunteer setting, so, but this is really just to give folks a sense of where we are as in engaging the mechanism. Again, we're still dose escalating, so.
Okay, fantastic. Just a couple of minutes left, so I wanna hit on going back to bitopertin.
Yeah.
It's a phase I study in Diamond-Blackfan anemia.
Yes.
Maybe just quickly talk about that.
Yeah. So we think heme synthesis, control and modulation, like that's an entirely new approach to treating hematologic diseases, so there is a long life cycle of additional indications we plan to pursue. DBA is the first one. It's, again, an orphan disease, very serious, patients are severely anemic. They're almost universally intensely transfused. The reason why there's a role here is, you know, just as in EPP, where we take down glycine uptake to control the accumulation of this toxic metabolite, protoporphyrin IX, in the case of DBA, you have this abnormal pathophysiologic accumulation of heme. So red blood cell production, typically, heme production and globin production is very, very tightly coordinated, but in the DBA setting, globin synthesis is compromised. So you have this unpaired heme that accumulates, and that's toxic to developing red blood cells.
So by controlling the amount of heme, toxic heme that's being accumulated, the hope is to be able to allow red blood cell production to be more productive. And so, you know, initial in vitro and in vivo work has shown that, you know, this actually works quite well. If you can take down heme, you end up getting better. You're able to address this ineffective erythropoiesis that is, you know, a core component of DBA.
Okay, excellent. When can we expect data for that?
We have not formally guided-
Okay
... but the guided to that, but the study is ongoing. It's in collaboration with the NIH. And so if we see a signal, then yeah, we'll be able to proceed from there.
Okay, fantastic. And then, I know we only have a little bit of time left, but one last question, moving now to polycythemia vera.
Right.
Just, just really quickly, what is the, what's the unmet need here and kinda ultimately, what would be a good profile?
Yeah. So, enormous unmet need. There's about 160,000 patients in the U.S. with polycythemia vera. And these patients still develop thromboembolic events from this uncontrolled erythrocytosis. There's only one, you know, branded, approved drug for this, and that's ruxolitinib Jakafi. It's in the refractory setting, but there's a whole swath of patients before you get there, before you get to needing Jakafi, who still live with the disease, who still have uncontrolled hematocrit levels, who are still at risk for thromboembolic events. So being able to have an agent that's able to control erythrocytosis, that is non-cytoreductive, that is a large group of patients who could benefit from that. And that, our third program is designed to be able to control erythrocytosis by restricting iron.
Excellent. Okay. Well, thank you very much. I think we're out of time.
Yeah.
Jonathan, appreciate it.
Yeah, thanks a lot, Ben. Appreciate it.