Ready.
Okay, hi, good morning. I think it's still morning, everybody. I'm Kristen, one of the Biotech Analysts at Cantor. Very happy to be hosting Disc Medicine. We have Dr. John Quisel from the team here. Thank you so much for taking the time to come to our conference today.
Thank you. Great to be here.
Yeah, lots of exciting things going on at Disc Medicine. But to start, I'll ask you the same generic, boring question, just to give us a high-level overview of everything going on, and then we'll jump into some specifics.
Yeah, it's an exciting moment at the company. We are obviously working on treatments for diseases that arise in the red blood cell compartment by manipulating iron and heme metabolism. Our lead program, bitopertin, is... So as we head into the end of the year, a lead program, bitopertin, we're scheduled to file our NDA on an accelerated pathway in October, which then would set up NDA acceptance in likely December. And that would, of course, be then triggering for defining a PDUFA date sometime next year. So a lot of exciting regulatory activity around the bitopertin program as we come in towards the end of the year. And then our second program, DISC-0974, an antibody for mobilizing iron. The lead indication there is the anemia of myelofibrosis.
And we're projecting a data cut of the RALLY-MF phase II trial to be presented at ASH. And then, you know, meanwhile, other things in the pipeline, chronic kidney disease indication, some data coming. And our third program in polycythemia vera has gotten up and running, but no data to come right now.
Okay, great. Thanks so much. So let's kick off the discussion a little bit more on bitopertin and EPP-XLP. I think claims data have been something that's extremely useful, especially for rare diseases. And you have come up with about 6,000 diagnosed patients based on some of your own work. But can you help us first just understand what goes into collecting this data? Does the methodology account for patients that appear multiple times in the system?
It's a great question, right? So we live in this era where you can access a lot of information about rare disease patients, and it's really important for that setting. So the Komodo claims database is what's called tokenized, meaning that if a patient gets an EPP code coded to them in Seattle, and then they move to San Francisco and get an EPP code coded to them there, in theory, at least, it tracks that patient as one token, meaning it won't appear as two patients. It should appear as one single patient. So all that goes in. And when we've looked at this database, we actually see 14,000 diagnosed patients, and 6,000 of those we view as engaged, meaning they've had multiple claims or recent claims against that EPP code. So it gives us...
And then the great thing about it, actually, each claim comes linked to the physician who made that claim. So it gives you a roadmap if you want to go find the treating physicians that eventually will be marketing the drug to. It gives us a roadmap of where those physicians are, who they are, and how many patients they're likely to have and we're able to actually turn that into a rank order list and we now, at this point, have hired MSLs who are out in the field. W e've given them this list, rank ordered, with the mission of go engage with those physicians and start to confirm boots on the ground the claims data, that in fact, the patients exist, that this is not all just theory, but there's patients there.
So that work is ongoing and is going well. So far, actually, the numbers add up to about the same, to the same place. It's not necessarily precisely accurate translating from claims data to patients at a site, but in aggregate, the numbers are in the same ballpark.
So that's pretty fascinating. I don't know too many rare disease companies that have used this kind of roadmap. But maybe just to help us understand, because obviously the drug isn't on the market yet, right? So what are the MSLs specifically going to these doctors? Are they just saying like, "Hey, can you confirm how many patients you have? We're aware of drugs that maybe could be in the market in the future, and we'll come back to you at that time.
Yeah, yeah, exactly. I mean, what's the basis for conversation? Obviously, we can't be marketing the drug at this point. Absolutely not. So it's more of a disease awareness kind of effort, reaching out, saying, "Hey, have you heard of this disease? Do you have any patients with this disease?" You know, we do have an ongoing clinical trial, so there's at least a basis for conversation around trial enrollment, which is a great thing to be able to offer up. So it's those kinds of conversations.
Okay. Another thing that perhaps might make you different from other rare disease launches is sometimes when we think about diseases, we focus very heavily on the spectrum of severity. So maybe mild, moderate, severe, severe gets therapy first. One thing that we understand with EPP, from speaking to some thought leaders, is that while they also experience varying severity levels that influence the time to prodrome symptoms, the pain and attacks, it doesn't matter if you're mild, moderate, or severe, they can be really bad for everybody. So do you view this as really an indication where there's likely to be all comers on drugs versus just saying, "Hey, this is only for moderate to severe"?
Oh, yeah, I think it's all comers. You know, when you look at initial tolerance to light in our phase II trial, we had no cap on that, right? You simply had to be diagnosed with EPP. But I don't think there was anybody in the trial who exceeded about a two-hour tolerance level. So I think that tells you the people who are beyond that level of tolerance, and maybe there are some, you know, we don't know, they probably either never get diagnosed because they never have a pain attack, or it's so unusual for them to kind of cross that threshold that they don't feel the need to pursue a diagnosis or seek any medical care for the disease.
I think when you look at the claims database, you're probably looking at patients who felt sufficiently afflicted by their disease to continue to pursue through the diagnostic process to find a doctor who would think to give them the very simple test for diagnosis, trivial, PPIX in the blood, is very easy to test for. But you have to find a doctor and stick with it long enough to find one who thinks about doing that test. Otherwise, the patients unfortunately get sidetracked into a lot of, I think, unproductive diagnostic conversations.
Okay. So you're doing the work now to at least identify and know where the patients are. Assuming an approval next year, how much work do you think is going to be needed in terms of educating them about this drug? And is this going to be one of those launches where it's both skewed to patients calling up their doctors and saying, "Hey, I heard about this new drug," versus the physicians calling patients?
It's going to be everything. It is certainly an important thing for us once we've got a therapy available to try to make it available to everyone who needs it. And then that does require disease education and awareness of a new therapy, right? Because I think right now, the common experience for these patients is they get their diagnosis and they're told, "Well, you know, there's really only one approved therapy. It requires surgical implantation." And you don't really get a lot of traction with that. And so the patients get diagnosed and they just go back to kind of light avoidance, living in the basement, avoiding all sunlight contact. So the question will be, how do you make these patients aware that, "Hey, it would be a good time to come back and see your doctor because there may be a therapy that could really help you now"?
That's the critical thing. When we look at our launch, I think the most engaged patients are the patients who are actually in our clinical trial, right? We expect about 100 to 150 patients in that category between our ongoing phase II open- label extension, the HELIOS trial, and then the rollovers off the APOLLO phase confirmatory trial. That's the 100 to 150 pool. We're putting a lot of effort into ensuring that those patients are able to smoothly convert from trial to reimbursed therapy.
Then everyone else will have to be new. And then, you know, no surprise, we're going to start at the centers of excellence, the top care providers in this field, where we already have very good connectivity, very well understand, very strong understanding of who those patients are. And then moving out from there to a broader community where it's going to become a mixture of boots on the ground as well as other more conventional marketing strategies to raise disease awareness and awareness of a new therapy that's arrived.
Okay, so I know there's a lot of excitement from the community, which has then resonated with investors, but how should we properly set expectations of the cadence of the launch, especially as things like reimbursement naturally take a little bit of time with rare disease drugs?
Yes, everything takes time. That is true, right? If we're, let's say we get, everything goes as planned, we get priority review, we're launching, call it middle of next year. As you say, even a patient who's in our long-term extension trial, you'd say, "Well, okay, they should be, you should be getting revenue right away," right? No, you have to basically get the payers to sign off on this. You have to have the prescriber write a script, everything has to come together. I mean, we're super excited about it and hope that we're able to get this drug to these patients as quickly as possible. Like you say, there can be delays and the ramp can take longer than expected.
Okay. So if you are also approved, how will patients be coached by their physicians to attempt more exposure and sunlight and become increasingly more comfortable over time?
Yeah, great question. I mean, we need to get our label, right? That's going to define the kind of coaching that we can do. Physicians, of course, can kind of coach however they want. But if you look at our data, what you see is that PPIX levels start to drop right away, but they don't reach their new minimum until about six weeks on therapy. So I suspect that a physician would look at that and say, "Hey, here's this new therapy. You should start taking it, give it a week or two, and then, as you say, start testing yourself," right? If you go outside normally to take your child to school and that gives you 15 minutes of sunlight exposure, think about spending a little bit more time and see how that feels, right? Yeah.
They all, I mean, believe me, from all the feedback we've had from patients, they've lived their whole lives worried about their sunlight exposure. They have a mental clock running all the time. So when you ask them to think about spending a bit more time, that's not a complicated question for them to address. That's just a modest change in their regular life.
Okay. Just on the open label extension opportunity alone, do you have a sense of how many patients may be in that program by that time next year that, again, to your point, it will take time for payers to sign off, but naturally, those are patients that we might expect could try to get on commercial drug?
Yeah, yeah. So we had great traction in our open label extension from phase II. We have about 85 patients in that. Now, ballpark, 15 of them are coming from Australia. So if you look at U.S. only right now, we're about 70-ish, 60 to 70 patients that are U.S. And then we'll have another 100 or so out of the 150 in the APOLLO trial. So that gives you a total number of 150, 160 patients.
Okay. Are there any recent rare disease launches that you would either say are good comparators to think about this launch or a good playbook that you looked at in terms of where there could be synergies?
Yeah, in terms of comparisons, right? So if you just look at kind of how you launch into a rare disease, a company like Soleno in rare obesity definitely came out with claims data. We're using that to track some of the launch, guide some of the launch activities and I think overall went very well. I mean, I think there's been some bumps or whatever, but that's a pretty good comparable. And then if you just look at market sizes that are similar in nature, I mean, I think we've looked at HAE as being one that has a lot of similar attributes, both severity and patient numbers. And I think when you look at that, it's, I think, the potential here to be a very meaningful rare disease population that we're treating.
Yeah, we actually cover Soleno and hear that one as a comparator quite a bit, especially also because these are patient groups where there's just a huge dire unmet need while two completely different indications, but also you hear stories about these patients, like what the drug has done for their lives. I've heard stories about a patient buying a convertible car on bitopertin, which is kind of crazy to think that prior you were sitting somewhere in the dark, right?
Right.
So it's pretty awesome when you hear those stories and you hear directly from patients how meaningful that goes far above any disease scale, in my opinion.
We are very lucky to have strong patient advocacy groups here who are willing to share some of these stories with us and, yeah, keeps everybody in the company going.
Okay. So you have received regulatory alignment on the APOLLO confirmatory trial design. You've started it. Sometimes investors say, "Well, Kristen, is there some risks associated with this trial? What if it doesn't work?" Could you maybe help us understand why you designed the trial the way you did and why you're confident that it will be successful?
Yeah, I mean, like any drug development program, we used our phase II trial experience to design the pivotal trial. Numerically, in phase II, we won on every single clinical endpoint that we measured, which is great starting material. It wasn't that hard to look at that and say, "Okay, what would it take then to power it?" Right? We got very good information about the variability of the data of these data streams and the projected delta. The particular endpoint we ended up using, and I think one of the biggest learnings from the phase II program was that there is a placebo effect, right? For the first couple of months, patients coming into a trial with a lot of excitement, right? There's been enough, I think, buzz in the community about this new potential therapy coming that people come in excited, right? Naturally.
They're excited to see whether they can spend more time out in light. And I think almost everybody lives their lives well below that pain threshold, right? So there's a reservoir where patients can push themselves out into the light more. And so I think that's what we saw in phase II, this sort of increased exposure to light, even in the placebo group during the first month or two. And so we designed our endpoint to really look at the last month of time in light data on trial. And we project that we're exceptionally well-powered using that endpoint to detect a strong difference from the placebo group. And then moreover, we've been able to stratify now, not just by severity, but also by geographic latitude. So we've put a lot of bells and whistles into this confirmatory trial to maximize our chance of success.
And then we also have now PPIX as the co-primary endpoint, actually at the request of the FDA. And I think that's, I mean, p-value less than 0.001 in phase II, as my head of regulatory says, that doesn't need to be studied again, right? So I think we view that as very high likelihood that we'll win on that and then I think we've engineered it well to win on the time in light as well.
Yeah. I know it's just looking at the last month, but even factoring in, we know that regardless, these PPIX levels don't really go down to the plateau till about like five, six weeks anyway. So do you think for this trial experience, people will exercise a little bit more caution for that first month? Because regardless of which arm you're in, it's going to take time.
You may be right, actually. Right. That learning may have gotten out there, right? Some folks have made the point to me, "Well, you know, when you have two-to-one randomization, it actually really maximizes the placebo effect because people think they're on drug versus a one-to-one. So now we're one-to-one. Is that going to reduce the placebo effect?" Yeah, there are things that may. But actually, if you look at our data, once you're out to month four or so, the placebo effect is pretty much gone anyway. So I think just the fact of looking near the end of the study, we think that will well manage any placebo effect.
Okay. Well, this has been a truly awesome story to follow, and we wish you all the best. I know you're filing next month.
Yeah, thank you.
Moving on to DISC-0974, first, let's talk about MF anemia. Bristol had some recent phase III data for luspatercept that failed. What's the most important thing that we can learn from these data falling short, and why do you think DISC-0974 is a better drug to potentially address anemia?
Yeah, well, if you looked at the phase II data for luspatercept, they divided the patients into four quadrants, those who are less transfused or highly transfused and those who are on Jakafi and not on Jakafi, right? So kind of four quadrants. If you look at those quadrants, really only the patients who are in Jakafi showed a response rate above or around 30%. So there was a lot of heterogeneity in the way luspatercept was working in those patients, which already, I think, creates a level of uncertainty and lack of confidence in the phase II data. The way they chose to progress in phase III then was to pick only the best cohort of patients, which turned out to be this fairly rare, highly transfused and on Jakafi category of patients, and go after those, right?
The premise was, "Hey, 30% response rate, ballpark, you would have guessed a placebo rate of about 15%. You could power that with 300 patients." That would be right on the edge of what might win or not win, p-value in the end, 0.067, I think, was the number just on the fail side. I think the other thing going on there is that when you're trying to treat anemia in the most heavily transfused population of patients, that is just going to be a tough place to win. We've been really gratified by our phase I-B data that we showed at ASH last year, seeing that the drug is working basically across everyone that we're treating. But importantly, we're seeing it across even patients who are not being transfused yet. Whether or not you're on Jakafi didn't matter.
That sets, I think, a really nice kind of foundational group of patients where we pretty well know the drug is working. They enroll at very high rates. There's a high unmet medical need there, represents over half the anemic patients with myelofibrosis. That gives us a great starting point for a highly responsive group of patients where the treatment of anemia is plausible in people whose bone marrows are still functioning pretty well. That plausibility just diminishes as you get out to the most heavily transfused, where to be honest, we have, I mean, our response rate is good, but it's very sparse data at this point. I think it's two out of five, right? We'll see how that plays out in the larger data set.
But at some level, it doesn't even matter because it's a pretty rare and more difficult to treat set of patients. So I think that probably was a lot of the luspatercept challenge going into the, for reasons we can't explain, didn't really work anywhere else, but they kind of boxed into that most severe set of patients.
Okay. So keeping in mind, there's obviously different patient subgroups depending on these factors. So I know you're going to have more data this year at ASH. What makes it a win across all of these different subgroups in particular?
Yeah, well, you know, again, when you're trying to power a study and ideally you're aiming at about 300 patients, being above a 30% response rate is important for building confidence as you go into a pivotal trial. So I think we're sitting, call it ballpark around 50%. Would love to see that maintained. But anything above that 30% threshold is a good sign for us. So I think seeing that we maintain the response rate that we had in phase 1b, that's a big win. Like that is going to give us a huge head of steam as we head into pivotal trial work. If it degrades a little bit from there, that can be tolerated, right? It's not really a problem. So we feel like we're in great shape right now.
And I think the other exciting feature of the year and what we can bring to ASH, assuming again, abstract still to come out, but is the story about competition, right? How is anemia being managed in these patients? There was a theory that it was going to be managed with luspatercept, right? Now that trial has failed. So I think decreasingly likely that that's going to be the case. There was a theory that it would be managed with momelotinib, right? I think momelotinib has seen nice uptake, good launch there. But it's not clear whether that really is fixing anemia or is more of an anemia sparing type approach.
I think what we've seen and discussed at EHA is that very strong enrollment of patients who are actually on momelotinib and remain severely anemic and looking for therapy from DISC-0974, and at least preliminarily, the drug is working in those patients. We came out with the kind of non-quantitative sense that it's generally working. I think we're really excited to come into if we're presumably presenting at ASH with a set of at least 10 patients who enrolled as a momelotinib combination and really be able to share that evidence that the drug works on top of momelotinib and what those momelotinib patients look like at baseline and how well their anemia is being managed just as a monotherapy.
So in a lot of ways, I view this year and this data cut as we come into the end of the year as kind of concluding the competitive market assessment, which we increasingly see as really being us as the only therapy on a path to be explored and hopefully approved as a treatment for anemia in MF patients, which represents a population of about 22,000 anemic patients in the U.S.
So, when you tie it all together, 2025, we learned a great deal about the competitive landscape, or now lack thereof. We're going to learn a lot more about your drug, especially with upcoming data. What are investors not getting here?
I think the last piece of the puzzle that we can't quite nail down for people is what is a phase III design going to look like? We're in this world where it's like pretty clear that the drug is working, particularly in the NDD population. Everyone wants to know, "Okay, then what is the phase III trial? How long is it going to take you?" So you can kind of get a picture of how that's going to unfold for the company. And while we can speculate and we have some sense of what the FDA will accept, we just can't actually define that until we complete our phase II trial. So I think that's the last piece to really nailing this down for the investor community.
Okay. Well, it should be soon after the data, so we won't have to wait long and hopefully that credit comes in. I know we only have a few minutes left, but I did want to make sure we could touch on CKD anemia briefly. Huge, huge, huge market. So I would imagine there's probably not one specific definition of how you can win here. So would love to hear your thoughts on that.
Yeah. So we've been running a phase I-B, SAD/ MAD program. Our goal is to present that complete data before the end of the year. It'll be either ASN or ASH, depending on some final timing things to be determined. What we saw last year, we showed single dose data from the 28, 40, 60 mg single doses. At 40 and 60 mg, we saw decent iron mobilization with one dose. I would say spotty conversion of that to hemoglobin response, right? We saw one or two good responders per cohort. On average, we were not reaching our target of hemoglobin increase of about 0.8 g per dL. The question will be, with multiple doses, do we get to that target? If we do, that's fabulous early data.
We're onto a kind of, call it, ballpark 50-patient phase II trial and kind of confirm that efficacy profile. The alternative is we're still not hitting that aggregate, but we have individual responders. That pretty much is what we already are sitting on, right, so pretty much you're going to get that or better, and then the question will be, well, can we define the responding population, right? If we can, then that also sets up kind of a ballpark 50-patient phase II-A-type study to really confirm the efficacy signal in what would be then a subset population, and then I would call like the dark- gray data category would be, yeah, we've got responders, but we can't actually figure out why they're responding.
That would be kind of like the more downside scenario of figuring out, okay, well then how do we run the next study? May require some time to think about that, or maybe it's not worthwhile, right? That'll be the decision point.
Okay. As I've always told you, the strategy to kind of have the catalysts like each half of the year, you always have something going on. So that's great. We love that. Keep it coming. But thank you so much for being here. We're very excited about all these readouts and the filing.
Thank you. Yeah, I appreciate all the attention. Yeah, thank you.
Thank you.