As a reminder, today's program is being recorded. Now I'd like to introduce your host for today's program, John Quisel, CEO. Please go ahead, sir.
Welcome to the Disc Medicine Myelofibrosis Anemia Day. As a reminder, this is John Quisel speaking, CEO here at Disc. I'm here with Will Savage, our Chief Medical Officer, and Pamela Stephenson, our Chief Commercial Officer. We are thrilled to be joined by Dr. Prithi Bose and Dr. Aaron Gertz, two leading physician scientists in the myeloproliferative neoplasm space. I hope everyone saw our first quarter earnings release earlier this week. We are progressing well towards NDA filing with our lead program, bitopertin, for EPP patients. Today, we want to take a deep dive into our second program, DISC-0974, looking at the need for new therapies to treat anemia of myelofibrosis. Dr. Bose and Dr. Gertz are with us today to provide expert insight into the disease and treatment landscape. Before we get started, I'll cover a few preliminaries.
We will be making forward-looking statements, and these should be taken in context with respect to materials that we have filed with the SEC and have posted on our website. Additionally, bitopertin, DISC-0974, and DISC-3405 are investigational agents and are not approved for therapeutic use in any jurisdiction worldwide. Turning now to our agenda, I will give a brief introduction to Disc and an orientation of our portfolio. We will get right into the discussion. Dr. Gertz will provide an overview on anemia of myelofibrosis and what this disease looks like and means for patients. Dr. Bose will talk through the current treatment landscape and emerging therapies in development, including DISC-0974. Will will review the phase IB data for DISC-0974 that was initially presented last December at ASH, and we will speak to our ongoing phase II trial.
Finally, Pamela will provide insights on the anemia of myelofibrosis market opportunity. For those who may be newer to Disc's story, we are a hematology company, and our pipeline targets fundamental pathways of red blood cell biology. Our current pipeline focuses on heme metabolism with our lead program, bitopertin, and iron metabolism, which we will be focusing on today. While today's focus is anemia of myelofibrosis, by targeting these fundamental biological pathways, our portfolio is designed to address a broad range of hematologic diseases, from ultra-rare disorders to highly prevalent ones. This range of disorders is shown along the bottom of the slide. We are developing three clinical stage molecules. The first, bitopertin, is a small molecule GlyT1 inhibitor, which we are developing in a rare disease called erythropoietic protoporphyria. As we have discussed previously, we have completed a phase II program.
Based on that data, we have aligned with the FDA on pursuing an accelerated approval path. We plan to submit an NDA in the second half of this year. We also recently shared that our APOLLO Trial, which is designed to support full approval of the drug, is officially up and running. Our second asset, DISC-0974, is the focus today. This is a monoclonal antibody that suppresses hepcidin and mobilizes iron by inhibiting a target called hemojuvelin. We are developing it in anemia of chronic diseases with anemia of myelofibrosis as the lead indication. Our third program, DISC-3405, is also a monoclonal antibody and acts in the exact opposite way as DISC-0974. It induces hepcidin to restrict iron to a target called TMPRSS6. We plan to study this program in polycythemia vera and potentially other diseases of iron overload.
Here is all of that laid out in a pipeline chart. I'll just call out the ongoing trials for DISC-0974, which are a phase II trial in anemia of myelofibrosis and a phase I-B trial in anemia of non-dialysis-dependent chronic kidney disease. Focusing in on DISC-0974, again, the therapeutic hypothesis for this drug is around hepcidin suppression. By decreasing hepcidin, DISC-0974 makes more iron available to support red blood cell production, thereby enabling red blood cell formation, particularly in the setting of anemia of chronic disease. To provide a bit more detail, looking at the left-hand panel, hepcidin is the key hormone that regulates how the body stores and manages iron. More hepcidin means iron is trapped in the liver and spleen, with less iron available to support erythropoiesis.
By suppressing hepcidin, you can release iron stores, enabling better dietary iron absorption and enabling better red blood cell production. With this approach, you can potentially treat a wide range of anemias. In particular, we expect this approach to have application in anemias of chronic disease, as hepcidin tends to be elevated in those inflammatory disease environments. Now, looking at the right-hand panel to go through how DISC-0974 works, it's an antibody against a target called hemojuvelin, or HJV. This target is known from both human and mouse genetics as a critical and specific regulator for hepcidin expression. We know that HJV is functionally specific to hepcidin and iron regulation through genetic validation. There is a disease in humans called juvenile hemochromatosis, which is caused by knockout of hemojuvelin. The only manifestations of this disease are lower hepcidin and elevated iron levels.
We went into this program expecting this to be a clean target and a highly specific tool for modulating hepcidin. So far, the clinical data have supported this expectation. With this approach, we established proof of mechanism in healthy volunteers. Our goal was to go after initial proof of concept in the anemia of myelofibrosis and anemia of chronic kidney disease. We have now completed enrollment of the phase I-B portion of our MF study and have presented a proof of concept data set at the American Society of Hematology in December 2024. Will will review that data later today. Our CKD phase I-B trial is ongoing. We shared single-dose data from that study at ASN, the American Society of Nephrology meeting, last year. That data showed generally effects headed in the right direction.
We look forward to seeing that data set mature as we move into the multiple-dose portion of that study. Together, these data sets should give us a strong basis to potentially expand into other forms of anemia of inflammation as well. Now, before we get into the KOL discussion, I want to give some high-level context on myelofibrosis and the history of how this disease has been managed. Myelofibrosis is a blood cancer and has three main clinical manifestations: enlarged spleen, debilitating constitutional symptoms, and anemia. For a long time, there were no real treatments for myelofibrosis. It was all about symptom management, supportive care, and in the most severe patients, maybe trying some non-targeted chemotherapies or removing the spleen. With respect to anemia, the treatment would be blood transfusions. Many patients became dependent on transfusions, which are very hard on the body.
Eventually, drugs like the erythropoietins and danazol came along to help manage anemia generally. These drugs have been used off-label in myelofibrosis with modest benefit. As Dr. Gertz will discuss, anemia in MF is complex and multifactorial and is fundamentally tied to the pathophysiology and progression of the disease. The big advancement in MF treatment over 10 years ago now was ruxolitinib, a JAK inhibitor. This was followed by newer JAK inhibitors that have come behind it. Ruxolitinib has made a big difference in managing spleen size and constitutional symptoms in myelofibrosis patients. It is a myelosuppressive drug. In a lot of cases, it actually makes cytopenias, such as anemia, worse. There have been many approvals in this field. There continues to be considerable drug development in MF. Fundamentally, the way that anemia is treated in this disease has not changed.
Significant unmet need on this front remains for these patients. Our objectives for today's presentation are really to convey why a new treatment for anemia of MF is so needed and what a truly differentiated treatment would mean for this market. Our guest speakers will give an overview of MF anemia, the role of hepcidin in the pathogenesis of the disease, and the high burden on patients. Our speakers will turn to how anemia in MF is managed today, the limitations to current treatment options, and what a meaningful anemia-targeted product profile would look like. We'll then talk through the emerging profile of DISC-0974 based on our phase I-B data and how we aspire for DISC-0974 to be positioned in the market. Now, I'm excited to turn it over to our KOL speakers, starting with Dr.
Gertz, who will give us an overview of MF anemia. Dr. Gertz is a hematologist-oncologist at the Cleveland Clinic. He is also an associate professor at Case Western Reserve Medical School, running the clinical research office at their cancer center, and has been a principal investigator in many clinical trials for myelofibrosis, including Disc trials. Please go ahead, Dr. Gertz.
Thanks so much for the kind introduction, John. It's a pleasure to be with all of you today to discuss a very important topic and a topic that's near and dear to my heart, anemia in myelofibrosis, or also known as myelofibrosis-associated anemia. The reason that we talk about it is a couple of different things. One is it's a common problem in myelofibrosis. Two, it is prognostic. It is oftentimes difficult to treat.
We're going to cover all these topics here in the next few parts of the slide deck before we start to pivot on ways we can work on this anemia and make it better for our patients. Myelofibrosis, just to give a little bit of background, is a disease of abnormal proliferation of hematopoietic cells in the bone marrow. It's kind of odd to be thinking about anemia or low red blood cell count in a disease where there's overproduction of red cells. The marrow becomes diseased over time from all this overproduction and release of cytokines. That really inhibits the ability to produce adequate numbers of red cells. This environment in the bone marrow is very inflammatory. White blood cells are part of the immune system.
It makes sense that these deranged immune cells produce cytokines and other inflammatory markers leading to the development of fibrosis and this erythropoiesis. There's ineffective erythropoiesis because of the scar tissue itself, as well as the inflammatory cytokines. We're going to cover the mechanisms of the anemia in myelofibrosis in a few slides. Really, that is a hallmark of the disease. Kind of a unique thing we see in myelofibrosis is this thing called extramedullary hematopoiesis, or bone marrow cells outside of the bone marrow. The bone marrow becomes so sick and inhospitable, these bone marrow cells need to find other places to grow. Sometimes we'll see EMH, or extramedullary hematopoiesis, in the liver or spleen or adipose tissue. I recently had a patient who had EMH in a breast lesion.
We thought she had breast cancer, but it turned out to be just EMH from her disease. Of course, that's what the hallmark symptoms of constitutional fevers, night sweats, itchy skin, spleen enlargement, and other cytopenias. Although we're going to spend some time talking about myelofibrosis, I admit it is considered to be a rare disease. It is a chronic blood cancer or chronic leukemia with a prevalence in the United States of about 25,000 people. On average, patients are around the age of 65 at the time of diagnosis. The five-year survival rate is variable depending on different prognostic factors within one's given disease. On average, we take all patients diagnosed with myelofibrosis. The five-year survival rate is around 50%. A large number of these patients will ultimately progress to acute leukemia, or also known as blast phase MPN, where the blasts build up.
It is a very aggressive disease, again, akin to acute leukemia. The other kind of end consequence of this disease is frank bone marrow failure, where the bone marrow is so sick and deranged, it cannot produce adequate white blood cells, red blood cells, or platelets. Again, the therapeutic focuses for the three areas of therapeutic focus for this disease are really centered around what we see clinically. One are the constitutional symptoms: fatigue, night sweats, itchy skin, bone pain, weight loss. The other is splenomegaly, the other kind of key hallmark. Spleen can enlarge for a couple of different reasons. One, of course, is the development of extramedullary hematopoiesis in advanced disease. Also, the elevated cytokines lead to expansion of the splenic tissues.
This splenomegaly can lead to early satiety and even infarcts in the spleen, as well as increased splenic and abdominal thrombosis. Real important symptoms to address. Of course, the other thing and the reason why we're here discussing it today is anemia and other cytopenias. Anemia can result from a number of different factors, as we're about to talk about. Again, it's kind of the third of the triad of symptoms we approach in this disease. Anemia is prognostic. A patient with anemia will fare more poorly than a patient who does not have anemia. So much to the point where we actually include it in our most common prognostic models. Although this is a disease, it's a blood cancer, it's a leukemia, there are no staging systems.
We rely heavily on these prognostic models to determine who has aggressive disease and who has less aggressive disease. Hemoglobin, over and over again, comes up as a prognostic factor, so having a low hemoglobin. Even in the MIPS 70, our most advanced and modern prognostic scoring system that includes genetic mutations and high-risk factors of the like, still hemoglobin, or anemia moreover, remains as an adverse prognostic marker, even when age has fallen out of the model. Anemia is also a severe manifestation of this disease. The pathobiology really surrounds kind of four main points. One is ineffective erythropoiesis due to bone marrow fibrosis. The fibrosis takes up physical space within the bone marrow. There is suppression or treatment effect from JAK inhibitors. Dr.
Bose is going to talk a little bit about JAK inhibitors in the next portion of our presentation today. It is a common consequence of the most commonly used treatments. The spleen can become enlarged, as we mentioned before, and sequester red cells, leading to increased destruction of those red cells. Then, due to cytokines being elevated, we see anemia of inflammatory block via elevated levels of hepcidin. All these things can work together against the patient. The patient's anemia might be multifactorial. It may have some ineffective erythropoiesis due to fibrosis and adverse mutations. There might be splenomegaly. There may be high hepcidin levels. One treatment for anemia may not work for every patient. Having multiple agents to treat anemia is really incredibly important in this disease. As I mentioned earlier, this is a disease of inflammation.
Via a disease of inflammation, we see elevated hepcidin levels. This figure here shows that patients with myelofibrosis have elevated hepcidin levels. Think of it like a patient with rheumatoid arthritis or some other inflammatory disease where we do see the anemia of inflammatory block occurring via hepcidin. Hepcidin, again, being a master iron regulator, kind of plugs those holes and does not allow the iron to be available for adequate erythropoiesis. I already mentioned earlier in the presentation that not only is anemia prognostic, but it is prevalent. Roughly 40% of the patients at the time of diagnosis will have anemia, significant anemia with a hemoglobin less than 10. Within one year of diagnosis, 60% of patients will have significant anemia. Over the course of time, over one's disease course, virtually every patient will develop anemia.
That is really important because, again, it is prognostic and it relates to symptoms. When patients become transfusion requiring, that is extremely detrimental on their everyday quality of life. Patients will develop transfusion requirements. A quarter of patients at the time of diagnosis will be transfusion requiring. 45% of patients will be transfusion requiring within one year of diagnosis. Again, nearly every patient, if given long enough, if they do not undergo a transplant or pass away from something else, will require transfusions at some point, as this is a progressive disease. Kind of circling back to the story about anemia being prognostic, it is not only just prognostic in a general sense within prognostic models, but there is actually a dose-response curve to the anemia. We talk about effective medications having a dose-response curve where we increase the dose of the medication and we see the increase of effect.
The same thing happens with anemia. The more severe the anemia, the worse their survival is. The figure on the left here shows a survival curve for patients with no anemia. Every curve drops as anemia becomes more severe: mild anemia, moderate anemia, severe anemia, with associated median survivals dropping from 95 to 59 to 41 to 25 months. The same goes if you divide patients based on transfusion dependency or independence, where the survival drops with transfusion-dependent patients. Anemia, again, is prognostic as well as prevalent. Kind of circling in onto the anemia of inflammatory block, which again is a key component of the anemia in patients with myelofibrosis, hepcidin and ferritin levels are associated with worse prognosis and survival independent of other risk factors in patients with myelofibrosis. The higher the hepcidin level, the lower the survival.
That kind of points to probably a couple of different factors. One, it again relates to the anemia of disease, which again, of itself, is prognostic. It probably also relates a lot to the severity of the inflammatory response within the bone marrow microenvironment, thus a more deranged bone marrow, again, linking to inferior survival. Not only is it prevalent and prognostic, but there might be some more to the biology than just simply having a low red blood cell count. It does not take kind of too much of a conjecture to go from anemia to symptoms to a worsening quality of life. A patient who has anemia has increased fatigue, worsening physical functioning. They want to go up a flight of stairs but are short of breath by the time they get to the top.
They may have a limited ability to perform their roles, whether at home or at work. There's, of course, a psychosocial impact. Anemia is associated with worse mental health, lower social functioning, and reduced satisfaction with emotional roles. Also within the health care system, anemia, in addition to lost patient functionality and potential work hours within that of society, we also see more access to health care by patients who are anemic, more hospital visits, more visits, and more health care costs. Transfusions, in particular, are incredibly expensive and time-consuming. Think about it. A patient gets their blood drawn one day and they're found to be anemic and needing a transfusion. They got to get a type and cross.
It could take a few hours to get that type and cross done and then a few hours to actually get the red cells and get the transfusion. By the end of the day, a patient may have lost most of their light hours getting a transfusion. If that happens once a week or every other week, that can be a significant burden not only on the patient but on the health care system as well. As you may know, red cells are a resource that's scarce. The blood banks are in constant shortages. This puts a strain on the entire system when patients are getting lots of transfusions. To kind of sum things up here, anemia is a prevalent and severe and prognostic manifestation of myelofibrosis. Inflammation leading to elevated hepcidin and iron dysregulation is a key driver. JAK inhibitors help manage symptoms. Dr.
Bose is going to talk about that in a little bit. Can manage symptoms and spleen sites, but also can worsen anemia. Kind of the different bases of pathobiology for anemia and myelofibrosis. Anemia and transfusions are associated with poor prognosis and survival in myelofibrosis. Anemia symptoms significantly impact health care utilization and quality of life. All these are important reasons why we need additional and better therapies to treat myelofibrosis-associated anemia.
Thank you, Dr. Gertz. Switching topics to the current and emerging treatment landscape, I'll hand it over now to Dr. Bose, who is a professor in the Department of Leukemia at MD Anderson with a focus on MPNs. He has also been a key player in clinical development for myelofibrosis and other MPNs, including DISC's clinical trials. Please go ahead, Dr. Bose.
Thank you, John, for having me and allowing me to speak on this very happening area of the current and emerging treatment landscape when it comes to anemia of myelofibrosis. As you can see on this slide, just sort of taking a high-level view here, the goals of myelofibrosis treatment generally include shrinking the spleen, improving anemia, and ameliorating symptoms. As you can see sort of towards the middle of the slide, there are two endpoints that have traditionally been used, particularly in getting JAK inhibitors approved. Note that all four drugs currently approved for myelofibrosis are JAK inhibitors. These endpoints are, if you will, a bit tailored to JAK inhibitors, I would say. Frankly, these two things are their strong points: splenomegaly reduction and symptom improvement.
SBR35 is the percentage of patients who achieve a 35% or greater spleen volume reduction at 24 weeks compared to baseline. TSS50 is the percentage of patients that achieve a 50% or greater decrease in their total symptom score using one of the well-established tools. For example, the MFSAF has been used in many of the trials. There's also the MPNSAF, as you see on the slide here, again at 24 weeks compared to baseline. Now, for anemia, which is pretty much almost a hallmark of the disease present in like a third of patients that you heard from Dr. Gertz at diagnosis and then becoming increasingly prevalent to the point where everybody gets it at some point, we don't really have any drugs approved yet.
We do not have as well-established endpoints, although we are certainly going to talk about some that have been used in the earlier phase trials and also in ongoing phase III. The current treatment landscape, again, four drugs approved, all four JAK inhibitors, like I just said. For anemia, nothing approved yet. We all use erythropoietin and its analogs like darbepoietin. We use steroids. We use synthetic androgens like danazol. I do not myself use IMiD for anemia, but they have been used. Iron chelation can sometimes be used, of course, to offset some of the iron overload that comes from transfusions. There are, of course, many, many drugs being developed for myelofibrosis, some of which have an anemia focus and many of which do not.
As you see on the left towards the bottom, just some examples here, not intended to be exhaustive, but you have BET inhibitors, telomerase inhibitors, the type II JAK2 inhibitors, as well as what's known as mutant selective JAK2 inhibitors, also shown there, drugs that target mutant CALR. These are the driver mutations. This is an emerging strategy to try and target the driver mutations in a better, more effective way. Other pathways such as XPO1, which is nuclear export, selenexor, great example of that, and then naftamadlin, which is an MDM2 inhibitor. There are others. For example, there's a pimkinase inhibitor. There are other things. These are all drugs that are really not meant to be anemia drugs. However, they are rather meant to be drugs that synergize with the JAK inhibitors and give us deeper responses.
Now, on the bottom right, you see the drugs that are currently the players for anemia of myelofibrosis. Again, nothing approved, but Luspatercept is in phase III, highly anticipated results, fully accrued trial. We'll discuss some data on that in the upcoming slides. And then, of course, DISC-0974 and then elritercept, which is also a drug somewhat similar to Luspatercept. Moving on to the myelofibrosis anemia treatment algorithm. This is kind of taken from the NCCN guidelines or paraphrased from there. As you can see, I mean, there's no anemia and anemia. And remember, I said this before, that about a third of patients will present with anemia, and then everyone will get anemic at some point in the disease course. A good proportion will start to need transfusions. Again, Dr. Gertz covered all this.
As you see, if you focus on the portion of the slide that hones in on anemia, you could have a situation where anemia is really the only clinical problem. Now, granted, that is uncommon, but it is not a super minority of patients. In my opinion, it's anywhere from 10%-20% of patients where anemia is the only real issue. You also have patients who have the more traditional presentation. They have some symptoms. They have splenomegaly to some degree. We're looking at the management strategy, kind of big picture as to how we manage these patients today. Now, again, all four drugs approved are JAK inhibitors. What are they good at? They're good at spleen reduction, and they're good at symptom reduction. Momelotinib, in particular, is also good at anemia improvement.
Keeping that in mind, if you're just dealing with anemia, I would say, again, on the left, if we are just dealing with anemia, I would say my approach is using an ESA or danazol or luspatercept. Granted, that is off-label, but that is obtainable, and we often use it. If there are splenomegaly/symptoms, I will use a JAK inhibitor. I usually do not use a JAK inhibitor if the only issue is anemia. Moving on to the middle, if you have a patient who is doing well on their JAK inhibitor in terms of spleen and symptoms, you generally want to keep it, and you want to add something that can help with the anemia. Today, again, that would be luspatercept, danazol, or ESAs if that E4 level is low enough.
One may want to change to another JAK inhibitor, preferably one with an anemia benefit such as momelotinib or pacritinib. If they are on a JAK inhibitor and they are not doing well in terms of spleen and symptoms, it makes sense then to switch. In that situation, one would typically go to any other JAK inhibitor that they were not on as long as it has an anemia benefit. Basically, momelotinib and pacritinib would be the two choices there. There would be less of an emphasis, I think, in this situation on keeping the drug that is not really doing so good in terms of spleen and symptoms and adding something for anemia, although that could still be done depending on the exact individual circumstance. Ruxolitinib has been around for now 14 years in myelofibrosis. Certainly, a very, very good drug.
This is really the drug that revolutionized the care of these patients when it was first approved in 2011. What you're looking at here is data from the Comfort One trial compared to placebo in patients with platelets 100,000 and higher, intermediate II and high-risk patients. That is our population here where you had an SBR35 rate of 42% and a TSS50 rate of 46%, really very, very robust response rates there for both spleen and symptoms for ruxolitinib. I will say just quickly that there have been other phase III trials where ruxolitinib has been more of the comparator. Those trials, just to be fair, have shown a lower spleen response rate of around 30%. Symptoms, however, have looked really good in the 40s. Again, what's the problem with this drug? It causes anemia.
It does not improve anemia, and it causes anemia. In the first anywhere from 12-24 weeks, the anemia can be quite significant. It is actually the most common reason for physicians stopping therapy with ruxolitinib or interrupting it, reducing the dose. Anemia is absolutely something that limits the efficacy of ruxolitinib because it is a dose-dependent drug. In order to benefit from it, you need to be taking it, and you need to be taking it at an optimal dose. That becomes the problem when the drug causes anemia, and it often does. As you can see, 96% of ruxolitinib-treated patients experience some anemia, more than half are on a suboptimal dose. In the real world, if you look at ruxolitinib usage and dosing, it is often something like 10 milligrams twice a day.
That tends to be the most common dose, certainly not the 15s and 20s which you would hope for because those are the doses that were used in the Comfort trial. Then about half of patients will discontinue ruxolitinib within three years for a variety of reasons. Anemia, I already mentioned, is a major one, is the most common one. There are other factors such as the response just dwindling over time or certain adverse events for some patients, although generally a very well-tolerated drug. There are other drugs. There are four drugs, as we've been saying, fedratinib 2019, pacritinib 2022, and momelotinib 2023. These drugs do have some differences in their targets. Ruxolitinib, JAK1 and JAK2, fedratinib primarily JAK2, less JAK1, pacritinib only JAK2, no JAK1, but also IRAK1 and ACVR1.
Then momelotinib, again, like ruxolitinib, JAK1 and JAK2, but the anemia benefit coming through the ACVR1 inhibition by that agent. What you are looking at here in the tables is really just a high-level overview of the efficacy in terms of TSS50, which is symptom response, SBR35, which is spleen response, and then anemia response generally reflected by transfusion independence rate. The indications are shown as well. They are all line-agnostic. They are all generally for intermediate and high-risk. Fedratinib is intermediate II and high-risk. For pacritinib, the platelets have to be less than 50 for the current FDA indication. Momelotinib has anemia in its label. To sort of walk you through these numbers, ruxolitinib, I already told you these numbers come from Comfort One, which probably reflected this drug in its best light with SBR35 42%, TSS50 46%.
That was against placebo. Fedratinib, these numbers come from Jakarta, also against placebo. So 36% for spleen, 36% for symptoms as well. This is all at 24 weeks, just a reminder about that. Pecritinib and momelotinib is a little bit more complicated because these had multiple phase III trials. These were never compared to placebo. Populations were different. I want us to be a little bit careful about these. When you look at pecritinib, you're looking at a range of 7%-32% for symptoms and 9%-22% for spleen. I'll qualify that by adding that these only refer to the 200 milligrams twice a day dose, which is the approved dose. These are not all doses. These are restricted to that dose.
Also, basically, this is encompassing about three, well, actually, I should say two phase III trials where one, the PAC-203 trial where the lower numbers come from, was in a JAK-exposed population, whereas the other trial, PROCIS2, which was the basis for its approval and where the higher numbers come from, was more of a mixed population with some JAK-exposed and some JAK9. Now, momelotinib, again, similar concept, more than one trial, essentially two phase threes being included here as in the US label, the SimpliFI-1 trial and the Momentum trial. The SimpliFI-1 trial was a head-to-head frontline trial against drugs. For spleen, the number of 27 comes from that trial. For symptoms, the number 28 comes from that trial. Again, head-to-head, JAK9 against drugs.
The other numbers, the 23 for spleen and the 25 for symptoms, come from Momentum, which was the more recently done second-line trial against danazol in a JAK-exposed population. If we turn our attention to the rightmost column, it talks about anemia response in terms of transfusion independence. You clearly see that with RUX, you do not get a benefit, right? You see the minus 21%. People becoming transfusion independent on the drug. With pacritinib, they did report the proportion that became transfusion independent of those who were not transfusion independent. It is not the same thing as saying transfusion dependent. These were patients who were either dependent as defined formally or just requiring transfusions here and there. If you took those patients and you saw how many became independent, that number was 24%. That was from the PROCIS2 trial.
Then at the end, the momelotinib, this drug, of course, is best known among the JAK inhibitors for its anemia benefit. You can see that, again, across trials, there was a -2% to +17% change in transfusion independence rates. All right. Back to the anemia and kind of focusing in on that. Like I said, there are no approved drugs. We use ESAs if the endogenous E4 level is low, i.e., less than 125. If their transfusion burden is either zero or low, those patients can benefit. You can see here the response rate, 20%-30%, usually does not last very long, usually not very durable, maybe a year or two at most. Otherwise, in the right patient, certainly a good and easy treatment. Danazol, again, response rate variable, but sort of in that range.
Danazol was, by the way, the comparator against momelotinib in the Momentum trial that gave us a good data set about what this drug can and cannot do. You have got to be careful with this drug. Anyone who has had a history of prostate cancer, I would avoid it. It is an androgen after all, and it could certainly feed the prostate cancer. I am very careful in using it in those types of situations. It is a male hormone derivative. Certainly, there is a potential for masculinizing side effects in female patients. One needs to be careful about that. Hepatotoxicity also is real, and I have certainly occasionally seen it. If tolerated and in the right patient, it can be a useful drug.
Glucocorticoids, I mean, as you see, a good response rate, but certainly not something one wants to use for any length of time in patients with a chronic disease with anemia. Now, luspatercept, of course, quite exciting, already approved for MDS, as you know. A phase III trial completed accrual in myelofibrosis, and those results are eagerly awaited. We will touch on the phase II data, I think, in a subsequent slide. Again, these are the things we have currently in our arsenal and that we tend to add to drugs like ruxolitinib or pacritinib. I'm sorry, ruxolitinib or fedratinib. Even, frankly, drugs like pacritinib and momelotinib that have their own anemia benefit, it's not uncommon to have to add these drugs. I have several such patients.
As we look for a drug specifically for anemia of myelofibrosis, what are the attributes we would like that drug to have? On the left, it should work across severity levels of anemia, right? Transfusion dependent or not so or mildly so. It should work across the board. Should work on its own. Remember, we talked about that 10%-20% of patients who do not need a JAK inhibitor. You would want something for them. It should be able to work with any JAK inhibitor, not necessarily just RUX. Now that all four are seeing increasing use, it should work with any of them and should be able to optimize their dosing. This is probably most true for RUX.
RUX is a dose-dependent drug, and you want to be able to deliver 15 or 20 milligrams twice a day to get the, in fact, 20 if you go strictly by published models. 20 twice a day is the ideal dose of RUX that you want to be able to achieve. That can be hard because of the anemia. You would want to try and optimize that and, frankly, help the drug do what it is best at. Of course, we would want response rates that are superior to what we currently have. The portion of the slide on the right, I think we already went over.
That's just there to remind you of the current approach in those who are not on a JAK inhibitor or are on a JAK inhibitor and are either doing well in terms of spleen and symptoms or not doing well in terms of spleen and symptoms. Okay. Here we go with the investigational drugs. We have, of course, DISC-0974, the anti-hemojuvelin antibody that we are talking about today. We also have the activin receptor ligand traps, luspatercept and sotatercept. There are minor differences between the two, but in general, they are both activin receptor ligand traps. In terms of hemojuvelin, basically a positive regulator of hepcidin. This is an antibody directed against hemojuvelin, the idea being to downregulate hepcidin.
This is not through ACVR1 inhibition, as you heard, in regards to pacritinib and momelotinib, but rather through hemojuvelin, the only drug I'm aware of that does this. Again, the idea being to downregulate hepcidin production. If you downregulate hepcidin production, you essentially free up iron for the bone marrow to use for erythropoiesis with less iron then being sequestered in the reticuloendothelial system. You just free up the iron, basically. Subcutaneous administration every four weeks, phase II, currently ongoing. They have the optimized dose, and the phase II is rolling out right now or has started at this time. Patients who are transfusion dependent or non-transfusion dependent who are on a JAK inhibitor or are not on a JAK inhibitor. Really for all these different cohorts. Before we get to the response rate, moving across to luspatercept and sotatercept.
Those drugs are activin receptor ligand traps. What that means is that there are these ligands belonging to the TGF beta superfamily, which binds to the activin receptor. What you're really doing with the trap agent is that you're sequestering those ligands away and preventing them from interacting with the activin receptor. When you do that, you impact SMAD2 and SMAD 3 signaling and essentially remove the terminal block on erythropoiesis. These ligands through the activin receptor tend to suppress terminal erythropoiesis. You're sort of releasing the brakes on that and allowing the red cell maturation to proceed. In fact, luspatercept has been called an erythroid maturation agent. Again, subcutaneous, luspatercept, I've said several times, they've completed a phase III study. Sotatercept in phase II has been presented a couple of times now at ASH and EHA.
Now, with Luspatercept in particular, they did study different cohorts in the phase II, but the phase III is actually only studying patients on a stable dose of a JAK inhibitor who require transfusion. That's really what is meant by those green checkmarks for those boxes. JAK inhibitor, stable dose, requiring transfusion is the population for the phase III. However, in the phase II, they did look at all four scenarios. Elritercept also, earlier phase drug, so clearly does have some data in all the four different situations. JAK inhibitor or no and transfusion dependent or non-transfusion dependent. With the results portion towards the bottom, we also clearly show you here the number of patients we are talking about. The Luspatercept study a little bit bigger. This is all phase two.
There are no phase III data in the public domain from Luspatercept, just to be clear. This is all phase II here. As you see, for transfusion dependent patients, the endpoint is always becoming transfusion independent. That is shown here, 40%-80% with the DISC drug, Luspatercept, 26% in the RUX combination cohort. Remember, that's the one that looked the best and the one that Disc Medicine took forward into the phase III. The monotherapy giving you 10% there. Sotatercept 24%. Moving on to hemoglobin improvement. This is not your transfusion dependent patients. These are non-transfusion dependent patients talking about hemoglobin improvement. Also here, one needs to be really careful because as you look at different abstracts, different articles, you've got to really focus on how these improvements are defined.
In the spirit of fairness on this slide, we're really looking at the mean hemoglobin increase. Not an increase at every time point necessarily, but a mean hemoglobin increase over 12 weeks of one and a half grams at least, right? By that parameter, 50% for DISC and then 43% in the RUX stable dose patients for Luspatercept, 23% for Luspatercept on its own, and 21% for Sotatercept. That brings me to the end of my portion of this presentation today. Just to summarize the stuff that we went over, we have four JAK inhibitors approved. The strength of these drugs mostly lie in managing splenomegaly and symptoms. Of course, momelotinib is approved for myelofibrosis with anemia and certainly is a good drug for anemia.
However, ruxolitinib is by far the most commonly used, is in my view, the most potent of the JAK inhibitors in terms of spleen and symptom benefit. It also has a demonstrated survival benefit, which may be a class effect, but it has not been shown with the other agents. Ruxolitinib is a dose-dependent drug, as we've been talking about. In order to optimize the benefits of this drug, it is really important to be able to counteract the anemia that it causes and certainly does not help with an anemia-specific agent. We've discussed that we today have a few of these, nothing approved, but we have a few options that are all somewhat effective but have their limitations in terms of toxicity or durability of response and also just the response rate.
Clearly, there remains an unmet need for new anemia therapies that can work on their own, be combined with any JAK inhibitor, help maintain the dose intensity of the JAK inhibitor, be well tolerated, and obviously be effective for anemia. All of that certainly are what we are striving for. On the horizon, currently, we have three agents, the DISC-0974, that is the topic of today's discussion, and then the EMAs, the activin receptor ligand traps, luspatercept, and elritercept. Thank you.
Excellent. Thank you, Dr. Bose. That concludes our KOL discussion. Dr. Gertz and Dr. Bose will both be available at the end of the call for Q&A. Thank you both for joining and sharing your expertise. I'll now hand it over to Will to discuss the DISC-0974 clinical program.
Thanks, John. I'll start by reviewing our MS clinical program to date.
A couple of years back, we completed a phase I trial in healthy volunteers, which established proof of mechanism for reducing hepcidin and mobilizing iron through hemojuvelin inhibition. At ASH last December, we first presented the results of our phase I-B study in myelofibrosis anemia patients. That initial proof of concept data will be our focus here. At the end of last year, we announced the initiation of a phase II trial in myelofibrosis, which is ongoing, and we will share an initial readout from that study in the second half of this year. To touch briefly on the healthy volunteer trial, that was a single ascending dose design. As shown on the top right, we saw clear pharmacological activity with reduced hepcidin production and increased transferrin saturation, or TSAT, which showed us DISC-0974 was behaving as we had expected.
What was surprising is on the bottom right, with even a single dose in healthy volunteers who are not anemic, we saw a hemoglobin improvement at the 56 mg dose as compared to placebo. This told us that DISC-0974 is a potent suppressor of hepcidin and that drug activity could strongly translate into clinically meaningful increases in the production of red blood cells and synthesis of hemoglobin. We then moved into a phase I- B trial in MS anemia. As a reminder, here is what the trial looked like. There were 35 patients, all with hemoglobin under 10, and we included a wide range of backgrounds in terms of patients on or not on concomitant JAK inhibitors. We included the full spectrum of baseline transfusion requirements that included non-transfusion dependent and transfusion dependent patients.
As with healthy volunteers, we saw pharmacodynamics that were consistent across doses and in line with our expectations based on the drug's mechanism. DISC-0974 drove a greater than 75% reduction in serum hepcidin that was sustained throughout the treatment period. This translated into sustained increases in serum iron and increases in both reticulocyte hemoglobin and hemoglobin, and ultimately into hematologic response and improvement in anemia. Before getting into the details of anemia response data, I want to spend some time on how we defined anemia response for different patient segments. People with myelofibrosis anemia are typically categorized based on how frequently they require red blood cell transfusions. We show our data in three groups. NTD or non-transfusion dependent are patients who did not receive any transfusions in the 12 weeks prior to the study.
Lightly transfused or TD low patients had one to two units transfused over the 12 weeks of baseline. Heavily transfused or TD high patients had three to 12 transfusions over the 12 weeks prior to baseline. The majority of the evaluable patients in the phase I- B trial were NTD. In our phase II, we are expanding each of these cohorts to have 30 patients per cohort. The anemia response endpoints are based on consensus guidelines, and they also take into account our interactions with the FDA. For NTD, an overall response is a mean increase of at least 1 gram per deciliter sustained for at least 12 weeks. A major response is a mean 1.5 gram per deciliter increase for 12 weeks. For TD high, an overall response is achieving at least a 50% reduction in the number of transfusions required.
A major response is achieving transfusion independence or needing no transfusions over a period of 12 weeks. TD low is the same, except that we look at TI over a 16-week period instead of 12 since the baseline transfusion requirement is lower. Following our phase II data readout, we expect to have discussions with regulators to align on what would be appropriate registrational endpoints for each of these groups. For context, the regulatory path in TD patients is precedented, and the TI endpoint is well established. For NTD patients, there is no precedented regulatory endpoint. Based on our discussions with regulators to date, the FDA recognizes that treating anemia in symptomatic patients is important regardless of transfusion status.
We expect that a combination of hemoglobin response plus some indicator of clinical benefit, whether it is maintaining transfusion independence or showing improvement on a symptom score like fatigue, which has multiple validated instruments, will be acceptable. We will look at data for one of those PROs, the FACIT fatigue score, today. Starting with non-transfusion dependent patients, 68% saw any hemoglobin response greater than a 1.5 gram increase in hemoglobin. 59% achieved an overall response of the sustained 1 gram per deciliter increase, and 50% achieved the sustained 1.5 gram per deciliter major response increase. On the right, you will see the FACIT fatigue increased by around 6 points on average by the end of the study. This is a strong indicator that patients were feeling meaningfully better from a symptom standpoint.
Moving on to the TD patients with low transfusion burden, all evaluable patients achieved an overall response of greater than 50% reduction in transfusion requirement. Four out of five, or 80%, also achieved TI. We acknowledge that these are small numbers, and we look forward to a more robust data set out of the phase II cohort. For TD high patients, 60% achieved an overall response of greater than a 50% reduction in transfusion requirement, and 40% achieved TI. Again, here the numbers are small, and we're looking forward to the more robust phase II data that we're generating now. Regardless of baseline transfusion burden, we saw strong hematologic responses translating to clinically meaningful improvements in anemia. As mentioned, we included patients with and without concomitant JAK inhibitor therapy in the trial.
There were 13 patients enrolled in the phase I- B on concomitant JAK inhibitor therapy, and these patients fell into the non-transfusion dependent and TD high groups. Overall, 54% of patients on JAK therapy achieved a major hematologic response relative to their baseline transfusion status. So DISC-0974 is working well in the JAK inhibitor treated population, and the response rates for non-JAK inhibitor treated patients were right around the same ballpark. As we heard from our KOLs, it is important to be able to add an anemia treatment onto whatever JAK inhibitor regimen is best controlling the spleen and symptoms for a given patient. And there's also need for anemia treatment in patients who are not yet requiring JAK inhibitors. So efficacy in both monotherapy and in combination is meaningful. Finally, in terms of safety and tolerability, the profile was generally consistent with past data sets.
The related AE that occurred in two or more patients was diarrhea and was mild. The majority of AEs were deemed non-related. We have already shared the design of our ongoing phase II trial, but today we're excited to announce the name of the trial, which is Rally MS. This name is intended to reflect what we hope DISC-0974 can accomplish for patients, rallying a comeback to better hemoglobin levels, less fatigue, and less overall burden of anemia. Also rallying the broad community effort coming together to bring this program forward. We initiated this trial toward the end of last year, and we plan to enroll approximately 90 adults with intermediate one to high risk MS and anemia with or without concomitant JAK inhibitor treatment.
Note that there are 12 patients who are eligible from an analysis perspective to be carried over from the phase I-B at the phase II dose, which is 50 mg. The phase II has the same six-month treatment period and optional continuation of treatment. We are including three cohorts, NTD, TD low, and TD high, with 30 patients per cohort. We also have an exploratory cohort of patients on momelotinib or pacritinib and are maintaining flexibility to add additional exploratory cohorts. Interestingly, the fastest enrollment demand we have seen so far has been in the exploratory cohort from patients on momelotinib with anemia. At this point, there is a waitlist for that cohort, which we see as underscoring the outstanding unmet need for anemia targeted treatments.
From an endpoint perspective, the key metric of the study we are looking at in this trial is anemia response, which is defined by cohort and based on our discussions with the FDA and updated clinical guidelines. We expect to share initial data from Rally MS in the second half of 2025 and top line data in 2026. At that point, we expect to engage with regulators and get a clearer picture of what a registrational study would look like. Based on what we have seen so far, we expect a single phase III trial addressing the full range of addressable MS anemia patients, but the details will be driven by the Rally MS data and regulatory guidance. With that, I'll hand it over to Pamela.
Thanks, Will. As we have discussed throughout this call, anemia and myelofibrosis is a market with significant opportunity.
It is a serious condition with 22,000 patients in the U.S. who suffer from severe symptoms that negatively impact their prognosis and quality of life. There is a clear unmet need as patients and physicians contend with a lack of good treatment options for this burdensome disease. It is a well-characterized market with established treatment pathways that make finding patients and connecting with HCPs fairly straightforward. Finally, we expect to have a differentiated product with the ability to address anemia for the full spectrum of these 22,000 patients. As Dr. Gertz and Bose discussed, JAK inhibitors are the mainstay of treatment for the underlying disease of myelofibrosis. These products have seen great success in the market, generating about $2 billion in sales in the U.S. in 2024, with ruxolitinib as the long-standing market holder and the new alternative JAKs adding to that business.
However, these products have limitations, and there are patients who have either never tried a JAK inhibitor or have tried them and had to discontinue. DISC-0974 is designed to work across all patient types, addressing anemia in those on a JAK, those who have discontinued, and those who are JAK naive. We feel the opportunity for DISC-0974 spreads beyond the reach of JAK inhibitors to address all patient segments, representing a true blockbuster opportunity. Taking a deeper look at the unmet needs in anemia treatment, there are five key issues. First, patients need a treatment that works across anemia severity levels, which DISC-0974 is designed to address as it is being studied across all levels of transfusion dependence and independence. Patients also need a therapy that can work as a monotherapy or on top of their backbone JAK inhibitor, with the potential to optimize their JAK inhibitor regimen.
DISC-0974 has shown similar strong efficacy as a monotherapy and in combination with a JAK inhibitor, and will continue to be studied in patients both on and off JAK inhibitors with a range of JAKs, including momelotinib and pacritinib. Finally, patients need a therapy with high response rates, something that DISC-0974 has demonstrated to date with response rates of 40%-80%. Market research we have done with MS KOLs and treaters supports the significant remaining unmet need in MS and the strength of the potential DISC-0974 profile. Physicians rated the unmet need very high at a 5.5 out of 7 and highlighted anemia-specific treatments and reducing transfusion burdens as two of the greatest needs. Additionally, they recognize anemia and the fatigue caused by anemia as two of the top three most burdensome symptoms of MS.
When reviewing the DISC-0974 phase I- B data, physicians rated themselves highly likely to prescribe DISC-0974 for their anemic MS patients, driven by the unique MOA, the strong response rates, and the ability to use DISC-0974 across all patient types. Overall, we view anemia of myelofibrosis as a market with blockbuster potential, especially for a product like DISC-0974 that works across all patient segments and is designed to address the key unmet needs for anemia treatment. I'll now pass it back to John to wrap up.
Thanks, Pamela. To close today, I will emphasize that we view the DISC-0974 program in anemias of chronic disease, starting with myelofibrosis, as we focused on today, as a key engine of growth here at Disc and as an important part of our mission to bring new therapies to patients with hematologic diseases.
Hopefully, in today's discussion, it came across how significant the need is for better anemia treatments for myelofibrosis patients, how encouraging our initial proof of concept data is, and how valuable the product profile we are pursuing could be for this community. The 40-80% response rates we saw in this early patient trial are a big deal, and we are working to prove out the efficacy in a larger sample in our ongoing phase II study, the Rally MF trial. We expect eventually to proceed to a pivotal trial. Myelofibrosis is a relatively rare indication with 25,000 patients in the U.S., but the need is clear, and it has been an important testing ground for us to understand how DISC-0974 and hemojuvelin suppression may work in the broader context of anemia driven by high hepcidin and inflammation, which is a complication of many chronic diseases.
As we have discussed, we also have a phase I-B trial ongoing in chronic kidney disease, a much larger indication of 37 million patients in the U.S., about 17%-50% of whom are anemic. In the single dose data we shared last year at ASN, we are already again seeing expected drug activity translating to iron mobilization and changes in hematologic parameters. We are excited to see how that data set matures with the multiple dose data later this year. Altogether, stay tuned for key readouts this year in our first two indications, and look out for more to come in anemias of chronic disease. Now, zooming back out to our broader portfolio, I'll remind everyone that we have several other important milestones expected this year. Notably, our planned NDA submission for bitopertin in EPP in the second half of the year.
We'll also be starting the first inpatient study for our third program, DISC-3405, in polycythemia vera in the coming months. This is another exciting opportunity targeting a clinically validated pathway. As we gear up for our first potential FDA approval, we are fully funded into 2028 to execute on the bitopertin launch as well as advance the rest of the pipeline and potentially start to explore the next wave of development for our portfolio. Thank you all for joining today, and I will hand it over to the moderator for Q&A.
Certainly. Thank you. Our first question comes from the line of Thomas Smith from Leerink Partners. Your question, please.
Hey, guys. Good afternoon. Thanks so much for taking the questions, and thanks for putting together this really stellar event. A question for both clinicians.
I was wondering if you could just comment on what % of your patients are currently on momelotinib or pacritinib as a function of their anemia. And if you could just describe what proportion of those patients you think could still benefit from another agent like DISC-0974 on top of those agents. How many of the patients, I guess, in your anecdotal clinical experience still have residual anemia that needs addressing? Thanks so much.
Hey, Tom. This is John Quisel. Thanks for the question. So why do not we hand it over to our panel? Dr. Bose, are you on, and do you want to go first?
Yeah, sure. I am on. Yeah. Thanks for the question. So certainly, momelotinib and pacritinib are seeing increasing use. In my personal practice, momelotinib more so for anemia. I think of the two, it does a better job for the anemia.
I think if you're asking across my practice, which obviously means patients in different lines of therapy, right? There's going to be front-line patients as well as second and third-line patients. I think momelotinib and pacritinib together could make up about 30%-40%, let's say, with about 50% still ruxolitinib and maybe 10% or so on fedratinib. I do have some patients on that. These are, of course, only my JAK inhibitor patients. To be clear, there are other patients who don't necessarily need a JAK inhibitor and could be on something for really early MF or something purely for anemia. Coming back to the JAK inhibitor patients, like I said, say 50% ruxolitinib, up to 10% fedratinib, and then maybe 30% momelotinib, 10% pacritinib.
Going with that, generally speaking, momelotinib in particular usually suffices on its own for the anemia. However, as Will pointed out in his presentation, there are absolutely patients on momelotinib that require some more help with their anemia. For example, in my current practice, I have patients on momelotinib and luspatercept. Same with pacritinib. It is not always that those drugs in and of themselves are a fix for the anemia. Within the momelotinib and pacritinib patients, I think this was really your second question. I think the—I'm sorry? I think you're okay. Please go ahead. Okay. Sorry. Sorry. Email's coming through. I'll close that. Within the momelotinib and pacritinib patients, I would say up to 40% of them would need something else added.
This is, I think, largely because the use of these agents is often in second and later lines when the disease is worse, the anemia is worse. I would say, yes, I would say up to 40% could need an anemia agent as a partner.
Great. Thanks. Dr. Gertz, did you want to add anything to that?
Thank you. It's great to be with all of you today. Thanks, Dr. Bose. That was a great explanation. I agree that there is a dramatic need for this agent. I think the fact of the matter is that at some point, even if a patient does have an anemia response on pacritinib or momelotinib, at some point, they won't have a response anymore. I even had a patient on SimpliFi2. They were on momelotinib for eight years.
At that point, all of a sudden, the momelotinib was unable to support their anemia, and they needed additional agents. Even if in the short term there is a response to momelotinib or pacritinib, there will be some point in time where those agents do not support the anemia, and they will need something else. I think it was brought up in the presentation. We are always trying to maximize JAK inhibition, and a limiting factor is always anemia. I think an agent like this can help us maximize no matter what the JAK inhibitor is. You could definitely see this partnering with other agents, other JAK inhibitors, of course, to really maximize that benefit. I would even think beyond that, right? There is all this interest now in combination therapies and metal stat, all these other drugs too.
A drug like this, the DISC compound here, would play nicely with others given the side effect profile and could be a valuable, say, triplet in combination therapy or in combination even with something like a metal stat that could stave off the anemia in order to deliver more and more effective therapies.
Great. Thanks.
Thank you. Our next question comes from the line of Roger Song from Jefferies. Your question, please.
Great. Thanks for a very informative presentation. Thank you for taking our question. Maybe my question is a follow-up on the previous question. Understanding the patient, even if they are a new JAK inhibitor, they may still need an anemia agent like DISC compound at some point.
My question is, can the doctor give us some sense of what would be considered as a clinical meaning for those different patient segments like a JAK inhibitor naive or those patients on top of different JAK inhibitors, including those first-gen ruxo and then the momelotinib? Thank you. That would be helpful.
Thanks, Roger. Dr. Gertz, do you want to start on this one?
Yeah, absolutely. As far as I understand the question, really, it centers around what's the value there. I think I'm trying to wrestle with exactly what you're saying there, but I think, again, there's a good value in treating this. I think a lot of times when we have a patient sitting in front of us, we're trying to address everything, right? Kind of part of our brain is looking at the spleen and symptoms.
We're thinking JAK inhibitor, clinical trial, what have you. The other part's looking at, well, what are the more immediate consequences for the disease, like cytopenias? It's almost like two functions in our mind at once while treating a patient. Sometimes there are agents that can address both, right? Again, we've talked about pacritinib and momelotinib already. Really, they're almost two somewhat, I guess, independent functions. We know we want to maximize that JAK inhibitor therapy, whether it's first line or second line or third line, to address spleen and symptoms with these patients that we'll have. We also think about anemia. As I said in an earlier slide, virtually every patient over the course of their disease will develop anemia. Again, the therapies that we have available don't work for everyone, and they don't work indefinitely.
I would say that thinking broadly about this, there's a lot of opportunity there for new and better anemia-focused agents.
Dr. Bose, did you want to add anything?
Actually, could I request the person asking the question to clarify what exactly the question was? I thought it was maybe the added value or lack thereof over the JAK inhibitors. Was that the question?
Yeah, I can clarify. Just in terms of different patient population, they are JAK naive or used on top of the current JAK, what would be the clinically meaningful anemia efficacy for the DISC compound? Thank you.
Oh, okay. Okay. Yeah. As Dr. Gertz very nicely pointed out, something to remember in this disease is that we don't—it's not a cancer that you approach as first line, second line, third line, or by stage. In fact, there is no staging.
We really focus on the clinical need of the patient. As Dr. Gertz said, for many of our therapies, we know they do certain things well, but there are certain other things which are equally important that they do not do well or even worsen, right? In the context of ruxolitinib, an amazing drug for spleen and symptoms, it actually worsens anemia. I think you need this added efficacy across lines. You need it in front-line patients, but even more so down the line. Now, if you're asking what response rate would—and I think that's how I understood your question—like you're probably wondering what response rate to the DISC compound or another compound for anemia would be clinically meaningful to us. That is—I think that it's hard to put that in numbers. Again, you obviously want transfusion independence.
You probably at least want a hemoglobin of 8 or higher. I mean, higher would be better. You want to maintain that dose intensity, right, of your JAK inhibitor so that you're getting the maximum spleen response that you can because that is tied to survival. You want to allow your JAK inhibitor to do what it does best. Obviously, the anemia is a big limiting factor that you're trying to counter with these drugs.
Great. Thank you both.
Thank you. Our next question comes from the line of Kristen Kliska from Cantor Fitzgerald. Your question, please.
Hi, everyone. Thanks for hosting this, and thanks to the KOLs for your time. I think we spend a lot of our time thinking about how sometimes the current medications for MF tend to make the anemia effects worse.
I'm curious how addressing the impacts of anemia might potentially allow the other MF drugs to do a better job addressing the other symptoms of myelofibrosis that they are more targeted to.
Thanks, Kristen. Dr. Bose, do you want to start this one?
Yeah, sure. Actually, I think what I was just talking about flows nicely into this in the sense that, again, the four JAK inhibitors are somewhat different. They certainly are not all the same in terms of their strengths and weaknesses. I think momelotinib's greatest strength is anemia, whereas with ruxolitinib, it is spleen and symptoms as well as with fedratinib.
The point being that we know with ruxolitinib, which is the most widely used JAK inhibitor, the only one with a demonstrated survival benefit, that this drug requires an optimal dose or requires an adequate dose to be able to lead to the best spleen shrinkage, which then correlates with the best survival. To that end, it is important to be able to deliver an adequate dose of ruxolitinib, which in my view is at least 15 twice a day, 20 twice a day, even better. That is where these drugs that help the anemia and combine well with ruxolitinib could really help because, again, you're trying to optimize that efficacy. Also, I should mention that studies have shown that the most common reason for discontinuation of ruxolitinib is anemia. It is a frequent problem. It is an on-target effect of ruxolitinib.
It happens, and obviously, it's a problem for the patient. It's a problem for the clinician in terms of transfusions, etc. Often, ruxolitinib gets stopped or at least dose-reduced. That is impacting the long-term benefit, right? That is where these drugs can be very good adjuncts. Great.
Thanks. Dr. Gertz, do you want to add anything?