being here at the Jefferies conference. My name is Matt Taylor. I'm on the research team here. I'm pleased to introduce John Quisel, CEO of Disc Medicine, a hematology-focused biotech with three clinical programs, including the lead bitopertin, which will have updated data at ASH this December. So the floor is yours.
Great, thank you. Well, it's a pleasure to be here, and thank you to the Jefferies team for giving us a forum, and thanks to all of you for attending here on the last day. So we will be making some forward-looking statements. Those should all be taken in context with our SEC filings and materials on our website. So for those of you who don't know us, Disc, we went public through a reverse merger at the end of 2022, and 2023 has been a spectacular year, both for investors, with our share price up over 190% on the year, and more importantly, for patients. I, I think there's indications from our lead program, called bitopertin, of potentially transformative effects, in a group of patients called with a disease called erythropoietic protoporphyria.
And we'll talk about that more. So Disc, as was mentioned, is a company focused on hematology. Our approach is to look at the fundamental building blocks of red blood cells. That has led us to three clinical programs, all of which control the metabolism of heme or iron, and these, as you all know very well, are the critical oxygen-carrying components of red blood cells and really are processed through the body on a macroscopic scale daily. So these are powerful, large metabolic pathways in the body. And with these approaches, our intention is to address a wide range of disorders that arise in red blood cells. And as you'll hear, it ranges all over the map from some very rare and severe disorders to some very common afflictions.
So we have a pipeline of three molecules that are in clinical trials, and we have a series of data updates coming. We've had data across this year coming at the American Society of Hematology meeting in early December, and then, of course, more data coming next year as well. So this is our pipeline chart. What you can see from this is, with these 3 molecules, we have 5 different disease programs running. The lead program, bitopertin, we in-licensed from Roche, and the lead effort there in phase 2 is in a rare disease called erythropoietic protoporphyria, and I'll talk much more about that in a minute. Then we're also in a phase 2 trial on a rare anemia called Diamond-Blackfan anemia.
With our second program, DISC-0974, here we're controlling iron metabolism as an approach to address anemias of inflammation, and we had fantastic healthy volunteer data presented at conferences in 2022. This year, coming for the first time at ASH now, is gonna be some patient data from trials running in the anemia of myelofibrosis and the anemia of chronic kidney disease. We have a second-generation antibody called DISC-0998. That's still preclinical. And then we have a third antibody that is designed to restrict iron to treat disorders of excess red blood cell production. This we call DISC-3405. The target is called TMPRSS6, which has become a fairly popular target in the industry, and we just initiated a healthy volunteer study with that molecule, so that data will come in 2024.
So the big news, you know, we're a hematology company, the big thing coming is ASH, and we have a series of presentations. So for bitopertin, here in this EPP population, we'll have a significant amount of data now from an open-label trial, and for the first time, we'll be able to show data from what is the precedented regulatory endpoint that has been used for approval of the one approved agent in this therapeutic area. So this data should give people an insight into how this molecule is performing in this open-label setting and really sets the stage for placebo-controlled trial data coming early next year. Then on the DISC-0974 program, as I mentioned, for the first time, we'll be sharing patient data from both myelofibrosis and CKD patients, so it should be a very exciting conference.
So from here, I'll dive into our programs, and so bitopertin modulates glycine, and the disease we're taking aim at is called erythropoietic protoporphyria. So these porphyrias are all disorders that arise from defects in heme biosynthesis. The heme biosynthetic pathway has multiple steps, and if any of those steps becomes broken, the pathway will start to spin off toxic metabolites that are otherwise consumed in a normal person. And in this disease, the toxic metabolite is protoporphyrin IX. it arises from a defect in an enzyme called ferrochelatase. We protoporphyrin IX, PPIX, just to make it easier. You've probably noticed already the nomenclature in this disease is not easy to wade through. So we have the disease, we call it EPP, and this toxic metabolite we call PPIX.
So PPIX, it's arising in newly forming red blood cells as they attempt to make heme, and while they do succeed in making heme, so these patients are not actually anemic to any degree. They produce tremendous amounts of this toxic metabolite, and that, when exposed to the sunlight as the blood flows through the skin, absorbs solar energy and emits it as free radicals, heat energy, and the patients experience this enormous pain after just a few minutes of sunlight exposure. It's described as a feeling of burning from the inside, and these pain attacks are disabling for days on end. So this develops, you know. Patients are born with this. It develops in childhood.
They start to experience, you know, a day at the beach, where suddenly they are just devastated by extraordinary pain for days, and that leads to a change in the entire lifestyle so that everyone with this disease basically lives indoors and, you know, has the windows shut, light coming through windows, et cetera, can trigger these pain attacks. And then there's a kind of a silent danger to this disease as well. So protoporphyrin builds up in the hepatobiliary system and can lead to low-grade liver damage. So about a third of patients are living with evidence of progressive liver disease, and a small number of patients, it can lead to overt liver failure, which is, of course, a very severe and potentially fatal complication of the disease.
You can see in the images here, just how this transforms people's lives. There's really no great disease-modifying therapy for these patients. There's one approved agent called afamelanotide, marketed under the name Scenesse. It's a capsule that's surgically implanted every two months. It elutes a drug that induces tanning, and that in clinical trials has been shown to provide about a 50% increase in tolerance to light before a pain attack will strike. Certainly efficacious and kudos to that company for establishing the pathway by which one can get a drug approved in this indication. Speaking to, you know, the way the drug works, you can see on the slide, this molecule targets GlyT1, which is a transporter that brings glycine into newly forming red cells.
That glycine is actually the first metabolite consumed in heme biosynthesis. So if you inhibit that uptake of glycine, you will decrease the flux of metabolites through heme biosynthesis. The result of that, the last metabolite, protoporphyrin IX, that's the bad actor in this disease. The concept is you can decrease the level of that metabolite accumulating in the patients' bodies. And that's illustrated on the bottom, where bitopertin by suppressing glycine, is intended to decrease the buildup of, of protoporphyrin IX. So we, you know, proved that out preclinically in cellular and mouse models, and, based on the strength of that data, we were able to open up two phase II trials, an open-label study called the BEACON Trial for 22 patients in Australia, and a placebo-controlled trial called the AURORA Study for 75 patients, in the U.S.
And much of the excitement around this program has arisen from data we've been able to look at on an interim basis through the progress of the BEACON Trial across this year, and what we'll be presenting at ASH now is data from all 22 of these patients. What I'll review briefly here today is the data we presented in the middle of the year at the European Hematology Association. So the first objective of the drug and its intended action is to decrease the level of this toxic metabolite, PPIX. The literature would suggest if you can decrease it by more than 30%, it will have a major clinical impact in these patients. So we're using two doses, a mid-dose, 20 milligrams once a day.
It's a very well-behaved small molecule with a half-life of about 40 hours, and then we use a high dose of 60 milligrams. What you can see on this diagram is both doses are achieving meaningful reduction in protoporphyrin IX. If you pull them together, the mean is about a 40% reduction, you know, roughly 30% at the mid-dose, roughly 50-60% at the high dose. So we have the individual traces. First win for the program, showing that the drug is, in fact, able to reduce protoporphyrin IX by that target level of 30% in the patients. And so then the question was: How will this manifest clinically, right? The main manifestation of this disease is the pain that comes on sunlight exposure.
One thing that's interesting is these patients get a warning sign when they're about to have a pain attack, and they all know it very, very well because every day in a patient's life is about managing sunlight exposure as you move through a day's activities. Then when a patient is reaching close to the pain attack level of exposure, they will get a tingling or a minor burning in the skin that's called a prodrome that warns them this is coming. This has been used in clinical development as a tool to measure the tolerance patients have for sunlight. So what we do is every week, we ask the patients to go out and challenge themselves, so it's a sunlight challenge, and time how long it takes to arrive at the prodrome.
You can see these are two different patients, one treated at the 20 mg dose level, one at the 60 mg. At baseline, you can see 4.5 or 1.25 minutes before they get this prodrome. These patients have a very severe form of the disease, and, you know, we ourselves were astonished by this data. What you can see over the progression of the study, the shift from the red bar to the blue bar and the change in time. The blue bar. The red bars indicate patients had a prodrome when they went out into the sunlight. That is nearly universal with the disease. The blue bars indicate no longer experiencing a prodrome, meaning the patients went out into the sunlight and were unable to elicit a response to sunlight, which is the hallmark of the disease.
You know, we didn't even design this endpoint thinking this would happen because it's so universal to have a prodrome. When the patients didn't have a prodrome, those blue bars, there's no instruction for them as to what to do. They go out in the sunlight, they stand there for a while, they keep track of the time, and eventually they say, "Okay, what-- I got to get on with my life."... So you can see that, you know, they were able to go respectively four or six hours without experiencing any response to the sunlight at all. And after day, you know, after day 20 for one patient, after day 116, never again experienced a reaction to the sunlight. So this is the two first patients that came through the study.
At this point in time, they were the only two who had completed 6 months of therapy. The others were all under a 3-month point. Nonetheless, we tried to aggregate the data and look at some statistics, just to get a feel for whether these were outliers or whether these were representative. And, you know, it appeared that this is on trend with the patients earlier in the study. So you just see this steady increase in time, with decreasing numbers of subjects who were on study at this moment in time. The time to prodrome is going up, call it 4- or 5-fold, relative to baseline, and the time that patients are able to spend in sunlight in the course of their lives each week, also going up 3- to 4-fold.
On an aggregate basis, this appeared to be a robust set of data, improving the sunlight tolerance for these patients by a truly remarkable degree, really unprecedented. The safety was good. Many people will ask: Does this decrease hemoglobin levels? It actually does in healthy, normal people. That was, in fact, the observation that led Roche and us to probe the hematologic effects of the drug. In these patients, for reasons that are not worth getting into today, you don't see, that doesn't manifest as a decrease in hemoglobin. Instead, what you're doing is reducing the toxic metabolite, PPIX, and the safety was otherwise excellent. On profile, there's a mild dizziness, and headaches are often observed in the first few days that patients take the drug.
Those usually resolve without issue, and overall don't lead to any significant dropout rate. So that's the EPP story. At ASH, we'll be presenting, again, 22 patients of data now, rather than just the 15 with the two completers. So it should really add a lot of weight to this body of data that we've been unfolding all year. And then we're not done yet. We're now opened a study in this rare anemia called Diamond-Blackfan. I won't spend a lot of time on this here. Rather than a toxic metabolite, it's heme itself that's thought to be toxic. So heme, of course, is essential, is supposed to be paired up with globin to make hemoglobin. In Diamond-Blackfan anemia, globin synthesis is impaired, and so free heme builds up in newly forming red cells, leading to a heme toxicity.
A fairly straightforward premise would be by decreasing glycine flow into that pathway, you can decrease the accumulation of unpaired heme and address the underlying anemia. We have collaborators who've been working with patient explants, cells from patients with this disease. If you apply bitopertin to those cells, shown in the lower left-hand corner, you can achieve, improvements in erythropoiesis in vitro. And then there are mouse models, not very good mouse models, that have mutations similar to the DBA disease, and you see improvements in erythropoiesis in those, mice as well. So we're very excited about the potential for this. The trial just started in August, and, we'll expect data, some early data next year. We really think we're just getting going with this mechanism.
As I mentioned, heme biosynthesis is obviously fundamental to all of red blood cell biology, and so we've started with the porphyrias. We're moving now to diseases of heme toxicity, like Diamond-Blackfan anemia, myelodysplastic syndrome. Also, some forms of that have a heme toxicity component. And then from there, we'll spread to diseases of globin toxicity, as well as diseases of excess red blood cell production, like polycythemia vera. So a lot of room to grow with this program. So now I'll move to our iron control programs. Some of you may know our ticker symbol is actually IRON. That's because the company was founded around programs to control iron metabolism, another fundamental and macroscopic component of the red blood cell compartment. Iron metabolism is controlled by a hormone-like molecule called hepcidin that's produced in the liver.
In inflammatory disease, hepcidin levels become very high, and it traps iron, primarily in the spleen. It blocks uptake in the gut, and the result is that newly forming red cells cannot access sufficient iron, and you get a kind of anemia called the anemia, excuse me, of inflammation. So we built a portfolio with a molecule and antibody called DISC-0974, that is designed to suppress hepcidin and treat these anemias of inflammation by releasing iron and allowing red blood cell formation. And then we have a molecule designed to do the opposite, which is an anti-TMPRSS6 antibody. It causes elevated hepcidin, restricts iron, and that is useful in diseases where red blood cell production has reached excessive levels, like polycythemia vera.
There's now clinical proof of concept from other molecules that by restricting that iron availability, you can normalize or reduce the overproduction of red blood cells. So we have essentially our hands on what are really genetically defined targets that control hepcidin up or down to modulate iron as needed in a wide range of patients. So I'll start with DISC-0974. This is an antibody against a target called hemojuvelin. It's designed, again, to reduce hepcidin, elevate iron availability, and therefore enable red blood cell production in the setting of inflammation. Hepcidin is expressed from a gene called HAMP in liver cells. It turns out to be controlled by a BMP signaling pathway... and hemojuvelin is a really special and specialized member of this pathway.
So BMP signaling pathways are famously pleiotropic, tend to be expressed everywhere in the body, can modulate many, many functions. Here, we're just trying to control iron metabolism, and so the trick is: how do you achieve specificity? Well, hemojuvelin is a great target because it's known as a loss of function in humans, and also can be done in mice, and the effect of that knockout is incredibly selective. You get essentially a loss of hepcidin production and a release of iron in the human body or in the mouse, without really any other effects at all. So it's a very selective regulator and a very powerful regulator of this pathway. Hepcidin has been a target of interest for over a decade.
The genetics predicted that this would be the best way to control that, with the widest therapeutic index, and we've now run, as I mentioned, healthy volunteer studies with data that can be compared apples to apples against other such programs that have been tried. I can say objectively, it appears to be the best such molecule to come along. This is some of our healthy volunteer data in the middle. You can see the different doses we use. These are fixed doses, not mg per kg, so we're working in very low doses. It's a very powerful antibody. We went from 7-milligram dose up to 56-milligram dose. You can see at 56 milligrams, we now have profound suppression of hepcidin in the left-hand panel, and the consequence of that in the right-hand panel is profound release of iron into the body.
It's measured by something that's called transferrin saturation, or TSAT, and we have it now shooting up well above the upper limit of normal. So that level of reduction, 75% suppression of hepcidin at that 56-milligram dose, is unprecedented. And also never seen before in a healthy volunteer study with this kind of iron-mobilizing agent, is an improvement in hemoglobin levels. So we saw a gram per deciliter over the placebo group on treatment here. This is unanticipated because these patients don't have an iron problem, right? So we're able, by just providing more iron, to drive additional red blood cell production in a healthy, normal setting. This gives us tremendous confidence as we progress into diseases where these hepcidin levels are actually pathological and these patients have an iron problem.
We have tremendous optimism that we'll be able to control that hepcidin, release that iron in those patients, and achieve perhaps even a more powerful hemoglobin effect. So with that data, we've chosen two diseases to start. There are actually a whole host of diseases where this kind of anemia is problematic. Anemia of myelofibrosis, this is a very severe heme onc type indication, where it's relatively recently been understood that hepcidin is quite elevated and plays a significant role in the anemia. And that's now the study that we'll be reading out in the early stages at ASH. And then the anemia of chronic kidney disease. This is actually where hepcidin was discovered. As the kidney fails, hepcidin is eliminated through the kidney, right? So as the kidney fails, hepcidin levels naturally become elevated. It's a consequence of the disease.
There's also often an inflammatory component. So hepcidin levels become extraordinary, extraordinary high here and lead to a lot of the iron pathologies that these patients have. So two dose-ranging studies that we're running in these patients, and it's that dose-ranging data that we'll be presenting at ASH. For the first time, we'll have a look at whether this agent is able to deliver a hemoglobin benefit in the myelofibrosis setting. In the chronic kidney disease setting, well, it's just going to be a very early look at changes in hepcidin and iron to understand how the drug is working pharmacodynamically in these patients. And as I mentioned, this is...
You know, if we're able to prove this out as an efficacious therapy in these first two indications, it points to an entire portfolio of indications that could be developed, and we also have a second-generation molecule with an extended serum half-life. So we have some ability to deploy different assets across the different diseases as we unpack this biology. And then finally, our third program, an anti-TMPRSS6 antibody that we call DISC-3405. We just in-licensed that molecule this year, although we've been working on this target since the founding of the company. And we just put this into a healthy volunteer study, so we expect to have data coming next year. This, as I mentioned, is the opposite of DISC-0974.
Here, we're trying to increase hepcidin, limit iron availability, and thereby restrict red blood cell production or restrict iron loading in diseases where that's helpful. Primarily, the lead indication is, is polycythemia vera. And here, it's the same genetic pathway or same signaling pathway we're dealing with. And like hemojuvelin, TMPRSS6, there are loss-of-function mutations in humans, and the phenotype is, again, exquisitely selective. The only result is an elevated hepcidin level and a restricted iron. So these patients develop what's called an iron refractory anemia. So again, the human genetics providing the proof of concept and also an indication of safety, right? You can tell that if I take an antibody against this target, the safety profile ought to be pretty reasonable. And so the company we in-licensed this from had done some early PK/PD work in animals, showed profound suppression of serum iron.
They showed efficacy in a mouse model of beta thalassemia. I won't go through all this. This is a common model to test. This particular model has not predicted well performance in beta thal in the clinic, so that's not an indication of high interest to us, but it shows that the molecule is highly active in doing what it's supposed to do. So we're in our phase I SAD/MAD healthy volunteer study. We should be able to provide data from that next year, and then the plan would be to progress very rapidly into trials in polycythemia vera and potentially other indications of iron overload. So this is the company we're building. Three clinical molecules, all fundamental mechanisms in red blood cell biology, controlling heme, first to address the porphyria indications and then potentially expanding from there.
Second molecule to release iron and treat anemias of inflammation, data coming at ASH in the anemia of myelofibrosis and the anemia of chronic kidney disease. And then the third program, taking aim at polycythemia vera. So thank you for your attention.