Welcome to the final day of the Jefferies Healthcare Conference. It is my pleasure to introduce Chief Financial Officer, John Quisel. Whenever you're ready.
All right, thanks for the intro. Just to clarify, I'm the Chief Executive Officer, but my CFO is in the audience. Great to be here, and really thanks to the organizers, much appreciated for providing this forum. Okay, the slides are up, great. So thanks for coming out to the Disc Medicine talk. Some preliminaries we get going. We will be making forward-looking statements. These should be taken in context with our SEC filings and materials on our website. We'll also be talking about three different development stage programs. They're not approved as drugs in any jurisdiction. Okay, so Disc Medicine, we are a hematology company, publicly traded. We've been public since we went out through a reverse merger at the end of 2022.
And, we focus on ways to manipulate red blood cell biology by controlling the metabolism of heme and iron, which are of course, two of the key building blocks for red blood cells. And we've assembled a portfolio now of three clinical stage molecules that are attempting to treat a variety of hematologic disorders. So along the bottom of this slide, you can see the range of disorders we're going after, running from very orphan indications like Diamond-Blackfan anemia and erythropoietic porphyria, which is one we'll talk about a lot today, all the way up to very common afflictions that affect millions of people in the U.S. alone, like the anemia of chronic kidney disease.
So all of these are disorders that arise in red blood cells, and all of them have some mechanistic connection to the metabolism of iron and heme. So that's the portfolio we've built. For today's talk, I'm not gonna do an extensive introduction to the company or its products. For those of you new to the story, you might also want to look at our website, where we have a very comprehensive corporate deck. Today I'm gonna just use the time we have to essentially set the stage for our next data release, which is coming next Friday at the European Hematology meeting, EHA, and so we'll step through most of that today. But we'll do a little bit of introduction. So we do have a pipeline of three clinical stage assets. The lead program is bitopertin.
This is a regulator of heme biosynthesis, and this is our lead program. We're deploying it primarily against a rare disease called erythropoietic protoporphyria or EPP, and we recently concluded our phase two program, and are, you know, looking to progress this now into pivotal trials. The second asset is DISC-0974. This is a an antibody designed to cause iron release, intended to treat, broadly speaking, anemias of inflammation, where iron restriction leads to imperfect production of red blood cells, and therefore anemia. We've chosen two lead indications where iron restriction is well documented as a cause of anemia. One is the hematologic indication, myelofibrosis, the other is non-dialysis patients with chronic kidney disease.
Both of these are quite serious forms of anemia with relatively few therapeutic options, and with this program, we successfully completed a very successful phase one healthy volunteer trial, moved into these two patient studies. They're phase 1b/2 studies ongoing right now, and we'll be disclosing data from these across the year, also. Sorry. Then the third program, DISC-3405, newest in the clinic. This is another antibody against a target called TMPRSS6. We started our healthy volunteer work last year at the end of the year, and now coming up soon, we'll be sharing the first clinical data from this program. The intention here is to actually restrict iron, so it's doing the opposite of DISC-0974, and it's well documented that iron restriction can be useful to treat patients with a disease called polycythemia vera.
It's characterized by excess red blood cells that lead to risk of clots, and by reducing red blood cell production through iron restriction, that can be managed. This molecule is also potentially useful for a range of disorders of iron overload. So that's the clinical portfolio. Each of these molecules, as I discussed, has the potential to address a wide range of indications. That wide range of use arises from the fact that all of these are addressing fundamental building blocks of red blood cells. Okay, so as I mentioned, EHA 2024, one of the two big hematology meetings of the year, coming up. Our data will come out next Friday.
We will be having data across all three programs, so I'll do a brief summary here of each of those data releases, then we'll go through the programs and talk in more detail about expectations. So that lead program, bitopertin, as I mentioned, we concluded our phase two program, one open label study, one placebo-controlled trial. The placebo-controlled trial was called the AURORA study. It provided mixed results. We hit our primary beautifully. Key secondary was not statistically significant, but several other clinically meaningful secondary endpoints were hit. So the key question in the investor community has been, you know, how are we gonna progress this molecule forward? What path will we take?
So we've been spending our time since that April first readout, doing reanalysis of the data, and we've built complete conviction that this molecule is working, that the clinically meaningful endpoints that we hit on are telling us the true story, and at EHA, we'll be presenting some new analyses now that we have the full data set in hand... that really prove out that point and show a roadmap for the kinds of endpoints we can use in a phase III trial. And then rounding it out, but without a lot of new news, we'll be sharing the full dataset from adults who enrolled in the BEACON trial, which is our open-label study conducted in Australia. So that's the top line kind of concept for bitopertin data coming next Friday. DISC-0974, our antibody for the treatment of anemias and inflammation.
At EHA, we'll be sharing data from the myelofibrosis anemia study that's ongoing. Here, we shared data at ASH in December last year, only about 11 patients, relatively short duration of therapy at that point. Now we're projecting to have about 20-30 patients worth of data with longer follow-up, allowing us to do a rigorous assessment of response rates. And we'll be showing higher doses now. We're dose escalating in these patients, and we'll be able to look at the 50-milligram dose and beyond, which for those of you who saw that ASH presentation, you know, we were already at highly active doses. So looking forward to what these higher doses will provide. And then the third molecule, DISC-3405, as I already mentioned, now we'll have our first single ascending dose, healthy volunteer data presented next Friday.
And this will include looking at the elevation of hepcidin, the restriction of iron, where the goal is really to see about a 50% or greater restriction in serum iron levels that would predict well for therapeutic efficacy of this compound in the polycythemia vera patient population. So that's the quick overview of what to expect at EHA, and now I'll dive into bitopertin. So this disease we're taking aim at first is called erythropoietic protoporphyria. It's a rare and debilitating disease. Projections of prevalence in the U.S. range around 3,000. We've done and published now claims data research that shows, in fact, up to 14,000 claims or individuals making claims against that disease code over the past seven years, so probably not as rare as the academic literature would suggest.
A really terrible disease arising from a mutation in the heme biosynthetic pathway, leading to the accumulation of a toxic metabolite called protoporphyrin IX, or PPIX, as I'll refer to it in this talk. That metabolite, as it builds up, causes several kinds of damage in the body. So first and most immediate for these patients is photosensitivity. This molecule, as it's coursing through the blood, when exposed to light, becomes a highly active free radical, which then damages all of the surrounding tissues, including nerve tissue, leading to excruciating pain attacks, which are called phototoxic reactions. So that is the primary thing that all of these patients are wrestling with, is an inability to expose themselves to sunlight, which greatly disrupts, as you can imagine, all kinds of activities that many of us take for granted in our daily lives.
This molecule also is excreted through the hepatobiliary system, can crystallize there, blocking the bile flow, leading to damage to the liver, and actually, in rare cases, liver failure and even death. So it is a very severe disease and also leads to a considerable amount of psychosocial dislocation and anxiety. We've seen in the claims data extensive opioid use, so severe complications come out of this disease. There's no treatment that manages the underlying cause here, the protoporphyrin IX toxic metabolite. There is one approved therapy. It's a surgically implanted module that elutes drug that causes tanning, and that tanning leads to some barrier protection from the light and some symptom relief for these patients.
Our drug, bitopertin, therefore, the concept here is it's an oral pill, easy to take once a day, very good PK, and the goal is to get right to the root cause of the disease and reduce the level of toxic protoporphyrin IX. So that's illustrated in this slide. I won't spend a lot of time here, but fundamentally, this is the heme biosynthetic pathway shown along the top of the slide. It begins with glycine that's taken up by newly forming red blood cells to facilitate a massive campaign of heme biosynthesis that goes into creating hemoglobin in a newly forming red cell. Obviously, that's what makes the cell red. And the last metabolite formed in that path is protoporphyrin IX. It's supposed to be 100% processed into heme and then incorporated into hemoglobin.
The mutation in this disease blocks that last step, or partially blocks it, so that you get a buildup of that protoporphyrin IX compound. Bitopertin blocks the uptake of glycine at the very top of that pathway. Seems to be selective for the red blood cell compartment, and as a result, presents a very good safety profile. In passing, I'll note that we in-licensed this molecule from Roche. It has a 4,000-patient safety database, a really excellent and well-characterized safety profile. And so we're utilizing it in this rare disease to try to decrease the level of that toxic protoporphyrin IX metabolite. Okay, so our clinical program here, two Phase two trials, one open label called BEACON in Australia in 22 adult patients. And then, we ran a placebo-controlled trial in the US called the AURORA trial.
We've used two doses in both studies, a 20 milligram, which is a mid dose, a 60 milligram, which is a high dose. Both, again, have excellent and well-characterized safety profiles. These studies have read out collectively over the past year, with AURORA reading out at the beginning of April, just a couple of months ago. So the primary endpoint for the AURORA trial was this reduction of the toxic metabolite protoporphyrin IX. We hit this endpoint beautifully. We hit it in BEACON as well. Here, we're showing about a 40% reduction from baseline, about a 50% reduction relative to placebo. The academic literature would suggest that reductions of greater than 30% should lead to a major clinical improvement in these patients.
So we're very happy with this result, which shows the mechanistic activity of the drug and the reduction of that key disease-causing metabolite. So the one drug approved in this disease, called Scenesse, was approved using an endpoint called the total time in light on days without pain, basically over the course of the study. So this AURORA study was a four-month study. Patients keep a diary of the time that they spend in light, and then you total up that time to arrive at a number. And the idea is that if patients are having a reduction in protoporphyrin IX, they should have increased tolerance for light and therefore choose to spend more time in sunlight. So on this endpoint, we were able to show that both dose groups, 20 and 60, did numerically outperform placebo.
But this placebo effect observed here was far beyond what had been observed in the handful of prior studies. Very much caught us by surprise. What we appreciate now is, you know, the prior studies with these drugs that work through tanning are, you know, have been noted in the literature as being functionally unblinded, whereas our studies are truly blinded. Patients cannot know whether they're on or not on bitopertin. So this probably creates something we need to manage in future studies. So this endpoint, you know, didn't work out as expected in this study, but several endpoints did. So obviously, one of the key parts of this disease for patients is these phototoxic reactions, these intense pain attacks that occur on exposure to light.
So this pre-specified secondary endpoint, we showed with the high-dose 60 milligram, 75% reduction in phototoxic reactions over the four-month study. That's relative to the placebo group. It was highly statistically significant in this study. And so this shows, I think, a real effect of the drug and something that's important for these patients, reduction of these pain attacks. And in passing, I'll note that this endpoint has been very robust across both trials we've run. In the open label study, we showed a greater than 90% reduction in pain attacks relative to baseline. There, we didn't have a placebo group. So this was one of the most promising parts of the AURORA Phase II data package. Then we also looked at quality of life surveys.
Here, numerically on both types of standard QOL surveys, we showed numerical benefit from the drug at both dose groups and notably in the PGIC. "Since the start of the study, how would you rate the change in your EPP?" The 60 milligram dose showed nearly every patient who took the drug felt much better, and that was statistically significant relative to the placebo group, even though you can see that here also, we're picking up some substantial placebo effect. Safety was excellent. I won't dwell on this. The profile is consistent with everything we've seen before. People often ask whether through the drug's mechanism, we're going to be decreasing hemoglobin. And to emphasize yet again, you know, we do not see any changes in hemoglobin across now the 100 or so...
Well, actually 75 or so patients with this disease who've received the drug. So what's coming at EHA, right? So the key question with this mix of successful and unsuccessful phase two clinical endpoints is: what is the path forward? So as I mentioned, we've now had about a month and a half with the full data set. We've been able to conduct a series of additional analyses. These analyses tell us that actually, all of these clinically meaningful endpoints are probably working, and we can see strategies for managing the placebo effect. And I think, what we'll hope to communicate at EHA is exactly that.
Present some new analyses, give the audience some sense of where that placebo effect comes from, how it might be managed in a clinical trial, and what the range of endpoints are that we can use in a pivotal trial that appear to be robust in the context of this relatively small AURORA study, 25 patients per arm, and give some, you know, forethought to how we might design a pivotal study. I can say now, you know, our intention would be to progress with the 60 milligram dose. It's clearly performing better. And, and with just one dose versus placebo, you know, in a one-to-one type trial, we think we can really achieve good power, going forward. So that's the objective of, of what we're gonna see, next Friday at EHA, and, we'll define that endpoint path.
As we come into the second half of the year, we expect to have our end-of-phase two meeting with the FDA, and then if all is good, we'll look to progress this into a pivotal trial next year. So that's the bitopertin story. I'll quickly go through the other two programs. These are generally taking aim at larger indications. So DISC-0974 is an antibody designed to reduce hepcidin, which is the central regulator of iron, that then releases iron into the bloodstream, which can help facilitate red blood cell formation in diseases of inflammation, which are often marked by an anemia. So anemia of inflammation is a tremendous area of unmet need. There are millions of patients that fall into that category, and by and large, there are few therapies available today.
Our target of our antibody is a protein called hemojuvelin or HJV, shown in black on this diagram. It's a key but very selective regulator of a BMP signaling pathway in hepatocytes that is responsible for hepcidin production. So a knockout of hemojuvelin in mice or in humans, actually, leads to marked reduction, near elimination of hepcidin production and massive release of iron into the bloodstream. So we're trying to mimic that genetics with an antibody, and we can tell from the genetics, you should be able to hit this target as hard as you want without undue safety effects. Because, again, in the knockout, the only real effect is to see mobilization of iron, which is our therapeutic intent. So we think we've got a great target. Antibody provides good PK, stable inhibition. That's all been reported previously in our healthy volunteer studies.
We're the first to show with this kind of mechanism, a hemoglobin change in the healthy volunteer setting. So this has been a mechanism of great interest for well over a decade, and we think we've finally come to the clinic now with a really good tool that has a lot of promise. So we've taken this into two disease populations. These are both dose-escalating type trials, so we're characterizing them as Phase Ib/IIa trials, myelofibrosis and chronic kidney disease. Both indications are marked by elevated hepcidin and anemia. So myelofibrosis, a very severe heme onc indication. Estimates of patients in the U.S., 18,000. I think other companies now in the space are actually estimating higher, closer to 25,000.
The inflammatory component of this disease drives elevated hepcidin, which contributes to the severe anemia by restricting iron. So here the objective is to release that iron back into circulation and ameliorate the anemia. Chronic kidney disease, similar story, just a much larger indication. Here, the hepcidin becomes elevated partly because of inflammation, but also partly because hepcidin is cleared through the kidney. So as the kidney fails, hepcidin clearance decreases, and it becomes elevated to pathologic levels. So two iron-restricted anemias at ASH. I'll just quickly look at some of the data we presented in December at ASH. In the myelofibrosis patients, we had 11 patients on study at that point in time.
At a relatively low dose of 28 milligrams, this is fixed-dose subQ, delivered once monthly, we show in the left-hand panel, a very good suppression of hepcidin levels coming from a highly elevated state and squeezing essentially everybody on study down into the normal range for hepcidin. And then on the next slide, the consequence of reducing hepcidin like that, if you follow the red line in the left-hand panel, you can see serum iron is massively increased. So this actually was highly active, more active, in these patients than it was in the healthy volunteers. Great to see it. The right-hand panel shows it's sustained over time, and puts on a page the reduction of hepcidin, the elevation of iron. So the drug is pharmacodynamically active at this 28 milligram dose.
We took a look at the hematologic response, so here the goal is to treat anemia. We want hemoglobin to go up, and in patients who are receiving transfusions, the so-called TD patients, we would like to see a reduction in the transfusion burden. So in the left-hand panel, you can see that, four of seven evaluable non-transfusion-dependent patients showed marked hemoglobin increases above the 1.5 gram per deciliter increased threshold that is used in the field to indicate a response. So we have a 57% response rate per this calculation at this time in ASH, which is a remarkable response rate. The target is probably about 30%. So we're well beyond that, showing what would be essentially best-in-class.
Our message at ASH was, if we can replicate this data in larger numbers of patients for longer, it would seem to be a very significant drug, potentially for these patients. In the right-hand panel, this is transfusion-dependent patients. We only had two on study, and, of those two, one of them had a very nice, 12-week period where there were no transfusions. That's called a transfusion-independent response, or TI. So this results in a 50%, response rate, though admittedly in a very small N. So these data at ASH look great, and, safety was great as expected. Healthy volunteer data, by the way, showed no meaningful safety signals. We're headed to EHA, data on Friday, next Friday. We'll just be updating that data, from ASH in 11 patients.
We're projecting now to have data from 20-30 patients. We'll be looking at the same endpoints: iron mobilization, hepcidin suppression, hemoglobin increase in the non-transfusion-dependent patients, and reduction in transfusion burden in those patients who are receiving transfusions. And we'll be able now to look at a longer period of exposure to drug to really look at 12-week windows, which are the classic duration expected in order to count someone as a true responder. And so again, we're sitting at a 50%-60% response rate from ASH in a relatively small patient population. Looking forward to EHA and hopefully showing that we're able to sustain that kind of really remarkable response in this patient population. So that's the 974 program.
As an aside, I'll just mention that our study in chronic kidney disease is ongoing, and there we project to present the next data cut at, in the second half of the year. We're targeting one of the kidney conferences, such as ASN, which is at the end of October. So lastly, this 3405. Here, it's the opposite of 974 against a target called TMPRSS6. We want to increase hepcidin, limit iron availability, and therefore reduce hematopoiesis. It's in the same pathway as hemojuvelin. These are essentially the genetically defined off-on switches for iron. And preclinically, this molecule has performed beautifully in reducing serum iron, in mouse models of beta-thalassemia and polycythemia vera, both potential target indications. It has performed well, and we're now in the healthy volunteer study with intention to go into, polycythemia vera next.
So this year will be the year of healthy volunteer data, some coming at EHA next Friday, some coming at the end of the year, and then we'll move into PV next year, with other potential indications on the horizon. So that's the story. I won't go through the rest of this. Just to touch on the catalysts, many catalysts coming across the year, bunch of data across the portfolio coming now, and then data sprinkled through the second half of the year as well. And behind it all, we're very well-financed, roughly $340 million as of the last quarter report out, which provides a runway across the entire portfolio well into 2026. So thank you for your attention, and I don't know if there's any time for questions or not?