ASCO 2026 | DISC-0974, an anti-hemojuvelin mAb, for treating anemia in MF: results from the RALLY-MF trial

Well, there’s certainly a lot of great research being presented at this year’s ASCO annual meeting. And one of the studies of interest, at least in myelofibrosis, is the RALLY-MF trial. So RALLY-MF trial is kind of a first exploration, if you will, in earnest, looking at the treatment of myelofibrosis-associated anemia with DISC-0974. And so I’m going to take a couple steps backwards. You know, anemia is really important in myelofibrosis for a lot of reasons. It’s very common. Roughly 40% of patients will be anemic at the time of their diagnosis, and virtually every patient will become anemic at some point in time. Two, it’s prognostic. Worse anemia equates to worse outcomes. It’s part of our diagnostic criteria. It’s part of our prognostic models. It’s caused by our treatments sometimes, like ruxolitinib and other JAK inhibitors can lead to anemia, so it can impair therapy even. And it’s multifactorial. Building on that other thought is it can be due to JAK inhibitors or other treatments. It can be due to dyserythropoiesis in the bone marrow. It can be due to inflammation, which is key, on how DISC-0974 works. 

So we know that in myelofibrosis, cytokine levels are high, particularly IL-6. IL-6 can drive hepcidin production. Hepcidin is the master iron regulator in our body. I like to think of it as a cork inside the iron wine bottle. If there’s lots of corks, all the wine bottles get plugged and none of the iron, or wine in this case, can get out. But if we can lower the number of corks floating around, more iron, or wine, will get out of those bottles being made available for red cell production or consumption. So we look at patients with myelofibrosis, particularly those who have anemia related to myelofibrosis, we see these high hepcidin levels. And this is not something that’s new. This has been targeted before. We look at drugs like momelotinib that block ACVR1, which is upstream from the gene that encodes hepcidin. And by blocking that pathway, we can lower hepcidin levels, thus making iron free and available for red cell production. And we do see that in trials like MOMENTUM, where we saw anemia improvements in patients with myelofibrosis. 

DISC-0974 takes a little bit different approach, but it’s working on the same pathway. So there’s this whole glob of things that come together called the hemojuvelin complex. One of those things is ALK2, also known as ACVR1, the target for momelotinib. But what 0974 does is it blocks hemojuvelin, that complex, in a different place, but has the same end result, blocking this complex, which controls the transcription of the HAMP gene, which encodes for hepcidin, thus lowering the levels of hepcidin. The advantages of a monoclonal antibody, though, that DISC-0974 is, is the fact that it is dosed less often. You can give it, you know, as infrequent as once a month and still have the desired effect. And it’s on target all the time where, you know, you give a pill like momelotinib and there’ll be this on target effect for a few hours. And then it wanes as the drug levels wane from the body. But getting a monoclonal antibody, you can keep nice steady inhibition of that pathway that’s continuous. So it makes a lot of sense to develop an anti-hemojuvelin antibody or other drugs that target this complex in this way. 

So specifically DISC-0974, this data has been presented before. It’s not necessarily new. It’s just an extension and continuation of these results that have been presented at this Congress and other Congresses. And what we’re seeing are a couple of really key important points. We see anemia improvements in all situations, right? So patients who are on a JAK inhibitor, patients who are not on a JAK inhibitor, patients who are transfusion dependent and patients who are transfusion independent. And I think that’s really important. We’re seeing responses across the board. Even when you break it down in transfusion dependent patients to patients who have lots of transfusions versus those who have fewer transfusions, we’re seeing responses in both categories of patients. We’re seeing responses independent of the time on a JAK inhibitor as well, which I think is important to know, because a short amount of time on a JAK inhibitor and the development of anemia is more drug-related, perhaps, where longer might be more disease-related. And so we’re seeing improvements in both. 

I think what we really want to see going forward from this study and others looking at this are those relationships. Do we see improvements in, say, hepcidin levels, which are very hard to measure, or maybe other iron metabolism markers and responses, anemia responses in particular? But really, really, though, what’s going to be next is RALLY-MF, it’s a smaller trial. It’s a proof of concept. We are seeing improvements in anemia, but we’re going to want to translate this into larger clinical trials, like prospective phase three trials that are going to be definitive, getting this drug across the line. And those trials are in process. So getting this early glimpse of efficacy is beneficial for planning those trials out and heighten our anticipation of those results to come.

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