So we're going to go ahead and get started. I'm Stephen Willie, one of the senior biotech analysts here at Steve Full, and glad to have with us from Disc Medicine Johnathan Yu, who is the chief operating officer. we're going to have a fireside chat. If there's any questions, feel free to raise your hand. We'll get your question asked and answered. before we jump into Q&A, Johnathan, any kind of introductory comments you want to make about the company?
Yeah, just thank you very much for having us here again this year, especially at such an exciting time in the company's growth. I feel like every year we're saying, oh, it's an incredible time for the company. It's a very incredible time for the company right now. You know, Steve Willie has been following the story for some time, so hopefully it's been gratifying for, you know, Carolina and other members of the team to sort of see this portfolio come together. For those who are new to the Disc story, we are a company focused on developing treatments for the, for serious and debilitating hematologic diseases. The name of the company is Disc, the shape of the red blood cell. The way we decided to construct our portfolio has been based on targeting pathways that are fundamental to red blood cell biology.
So we have programs designed to affect heme synthesis and programs that regulate how iron is metabolized, so iron homeostasis, by controlling a key hormone called hepcidin. So just very briefly, our lead program is called Bidapertin. It's an oral small molecule inhibitor of a target called GLIT1. It's designed to be treated to treat a, a rare debilitating condition called erythropoietic protoporphyria. And, that is a program where we recently submitted the NDA at the end of September. And then we were, very happily a recipient of the, one of the first recipients of the FDA's, Commissioner's, National Priority Voucher program. So, we're, that could potentially put us in a position to potentially commercialize at the end of the year, early next year. So really tremendous program, progress on that program. And then the other programs in the pipeline designed to control iron also have progressed extremely well.
They're both in phase two. the lead program there, in the iron portfolio is a drug called Disco 974. It's an antibody against a target called hemojuvelin. It decreases hepcidin and increases iron, and that's designed to be treated a variety of, potentially treated a variety of anemias. our lead indication is anemia of myelofibrosis, and we showed exceptional activity at ASH last year and follow-up activity at EHOP. And the first phase from the phase one B portion of the study and the first, the first, installment of the phase two data is going to be shown at ASH this year. And the last program is a drug called Disc 3405. It's an antibody against a target called Tempor S6. That's also in phase two, and it does the opposite of 974. It's designed to induce production of hepcidin and restrict iron.
There are a variety of applications for therapeutic iron restriction, but we're taking that into polycythemia vera initially, and we should have the first data readout sometime next year. So extremely busy time for the company.
All right, let's talk about all those things. so the CNPV award was a very interesting development. I think certainly recognition of the unmet medical need that exists in EPP. you did not have to initiate the investment of a $5 billion manufacturing facility to get one. It's even better. but so what are the benefits to you as a company now per this CNPV? I know you submitted the NDA in September. You've, they've talked about how this could be turned around in one to two months. how does this now set up for you? And I guess what are the, the position points that you're going to be disclosing kind of from here on out, right? Do you announce acceptance of the NDA? Do you,
Exactly. Yeah. I mean, this is a groundbreaking program, and like we're very honored to be a part of it. and one of the things that it does, and I think the primary advantage of this is, you know, this is what the FDA has said, is like accelerating the review time. So it cuts down the review time from 10 to 12 months to one to two months. And the way we sort of think about the cadence and the timing of that is it's a one to two month review period from when the filing is accepted. So thinking through, you know, the timelines, we submitted the NDA in September 29th, give it the standard 60 days for when the FDA would determine whether or not the filing has been accepted.
So sometime, you know, in the sort of November 29th, you know, timeframe, that would be put you at the 60-day mark. we'll be able to, you know, let folks know whether or not the filing has been accepted. And then from there, it's a one to two month review time period, you know, with, of course, the FDA always reserves the right to be able to take longer than that, but that's been the projected time, that, they said they would review the, the application. So that puts us in a potential approval window either at the tail end of this year, you know, December or, or in January. so that's, that's sort of how we think about, about the, the timeline.
And as far as the benefits that come along with it, one is like, you know, just, you know, greater communication with the FDA, but primarily the accelerated, you know, acceleration of like resources to be able to, to focus on the review in that timeline.
Okay. I think the, the outcome of the approval itself, I don't think is necessarily viewed to be a controversial thing amongst investors, and certainly not now post the, CNPV, but I guess we do have some discussions around labeling. and I know that you guys have the opportunity to maybe secure a, a pediatric review voucher. you do have some adolescent data. I think it's limited to four patients. Do you think this CNPV award somehow now changes the likelihood of you getting a broader label that covers adolescents?
Yeah, I think, you know, to be sure, I mean, I think, I think the drug certainly has applications in these, in the adolescent, you know, 12 and up. and our base assumption is that, you know, and our expectation is that the label would encompass adolescents, so 12 and up, and then of course adults as well. and we're seeking a broad, label to treat EBP and XLP. you do bring up the point that it is just four patients. I think that there is a pretty good case here though, because we've shown that the drug does what it's supposed to do, you know, lowers PP9 in these patients. In those four patients, the, the safety, the safety is extremely well understood broadly of the drug.
but, so I think we continue to believe that there's a good case to be made for, for, for the, for inclusion of adolescents. So, yeah, the, the biology of how Bidapertin works doesn't seem to be any different in adolescent patients.
And it certainly seems like there's some increasing scarcity value around these priority review vouchers, just given they're starting to get phased out a little bit.
Yeah, yeah, remains to be seen where, where the, where, where the things land with, with that. but, you know, I think, you know, even if it were just focused on the adult patient population, that is, that is where the majority of the patients are. So I think that there's still a very good, you know, certainly very strong business case. So it doesn't affect the overall thesis too much. But, but yeah, there's no reason to think that, you know, adolescents shouldn't benefit from Bidapertin.
Maybe we can talk a little bit about launch readiness, and just kind of where you are now in terms of building out your commercial infrastructure. Do you think that your teams that you have in place now are, are, are right sized? Do you have a lot more hiring to do?
we do have some hiring to do. So I think this is, as you can imagine, originally we were thinking, that, you know, a launch would be potentially in kind of the mid-year Q3 timeframe, and that was our original plan for, for the launch. you know, this substantially accelerates things. We are also accelerating, we are accelerating internally, operationally and getting ready for launch. But the way we're thinking about it is that, you know, if we are target, if we are thinking about a commercialization, the December, January timeframe, it's very unlikely we'll have Salesforce entirely, you know, hired and trained and deployed at that time. that said, we do have, you know, we do have the supporting, you know, commercial infrastructure largely in place. We'll be focusing primarily on building up our market access capabilities, and we already have an MSL, Salesforce and Medicare's team in place.
So I think the way to think about this is it'll probably be staged and kind of a, and kind of a staged approach where we'll be relying largely on our existing relationships and word of mouth early on. And then there'll be a wave too, once the Salesforce is trained and deployed, where, you know, true awareness and the classic things you think about in launch, we'll be able to leverage that sometime in mid-year.
And another point of leverage, I would imagine, is the fact that EPP has its own specific diagnostic code.
It does.
So that kind of helps you determine the volume of claims and maybe where those originating from. Where are you in the process right now of kind of identifying patients and mapping accounts?
Yeah, we're right in the middle of that right now. So you bring up a very good point in that, you know, the nature of the EPP, of EPP, you know, we're not starting from entirely from scratch. There is an ICD-10 code. There is rich claims data that allows us to be able to do more like kind of a surgical focus kind of, you know, account targeting launch. so I think, you know, what we're, what we're doing right now is, you know, relying on our, on our, on our MSL team to be able to qualify those accounts and to, and to help us prioritize where to focus initially. But, but yeah, so like that's, that's where we're in the thick of that right now.
Initial, initial read is that, you know, our data, that the data is sound and that we'll be able to, to be able to have a very bespoke targeted, early, early launch.
And so for those folks that are trying to think about, you know, what the trajectory of uptake here might look like over the course of the next 12, 18 months, how are you thinking about this notion of, you know, there's obviously a pre-identified pool of patients that could be candidates for therapy right off the bat. I know you have another 150 or so patients in open label extension trials that could become, paying customers as they convert over to commercial products. So how do you frame up, you know, what that trajectory will look like over time? Is there going to be a bolus of patients? Would you expect it to be kind of more measured as you build out infrastructure over the course of the first one, two, three quarters?
Yeah, I think if you look at, there have been any number of recent, rare disease launches in, in the last, you know, year or two, which I've shown. I think if you look at that, that trajectory, it's very similar as you say, like lots of these, lots of these conditions, and launches, they were able to rely on patients who are already, you know, in clinical trials, who are, you know, you're able to leverage, folks who are, you know, at, you know, centers of excellence. And then it's kind of a steady, steady eddy kind of growth.
So that's kind of how we think about it, in that, you know, there's going to be some word of mouth that's required long term to be able to sustain the long term growth, but we're also be able to use, as you say, patients who are in the clinical trial already. we have good relationship with patient advocacy groups and, and, you know, the center of excellence are important initial source of patients as well. So I think it's, there's no reason to believe that the, the, the launch shouldn't resemble some of these other, you know, early, rare disease launches.
Okay. And then I know you're trying to complete enrollment in the confirmatory phase three Apollo trial. Does the commercial availability of, of, of, Bidapertin somehow impact that at all, good or bad?
Yeah, I, I, we, we think, we, we don't think it'll have, a negative impact. I can totally see where that comes from, you know, if you have the drug available and suddenly patients don't want to be in your trial anymore. But, but you know, the trial has, has been open since, around May and, and, recruitment's going well. You know, we've basically given guidance before that it takes about a year to enroll the full study. and so I, we, we don't think it should be, should have a, adverse impact on, on, on the study completion.
Okay.
And just as a reminder, it's a global trial as well. So we also have European sites that'll be able to support, continued recruitment, for the study.
Okay. On the competitive front, you know, we know Cinesse has been in the market for a while. there's also a product from, Mitsubishi Tanabe that I believe they're guiding to data, before the end of this year. Just how do you think about maybe that product? and, you know, if that were to procure approval at some point, how do you think the, the two product profiles line up?
Yeah, I think, I think the biggest distinction between our drug and some of these tanning agents is that, you know, we would be the first agent if approved that affects the underlying driver of the disease. And so, you know, it lowers PP9, which is, you know, a photoactive molecule that accumulates in your body, and that's what causes the phototoxic reactions, you know, whenever patients go out into sunlight. And the data that we've seen so far is that our approach of lowering PP9 has this profound impact on photosensitivity. Patients, you know, patients, are able to spend more time in sunlight, their attacks disappeared at the end of the study, and then they felt palpably better.
So, and so far in our, patients who were on phase two, say there's been, you know, patients have stayed on the drug, there's been a lot of, you know, desire to stay on the drug. So I think all that says that the profile is, is, is very strong. and there is also a reason for patients to want to have a PP9 reducing agent because that has an impact long term, we believe, on the hepatobiliary complications, which these tanning agents will not have an impact on at all.
Okay. plans for Bidapertin outside the U.S.? I know you have some, some legacy economics here that, are owed to Roche. does that incentivize you to maybe try to do this on your own? do you think that this is something that you guys could do?
Yeah, I think that, EPP is, is one of these conditions where yes, certainly it's, and there have been many examples now where like if we wanted to go at alone, we certainly could. the timeline for XUS approval, is a little bit more delayed from the U.S. approval, particularly now with, with the CNPV. So the basis of any approval and jurisdictions outside the U.S. will be around the Apollo, with, with the Apollo data. But what we understand about the market, you know, outside the U.S. is that the structure is very similar to the U.S. in that it's also centers of excellence. you know, there are patient advocacy groups and, you know, there's already an infrastructure, outside the U.S. that we think could enable, a small company to potentially launch if we so choose.
Okay. I know you flagged other potential opportunities for this drug, one of those being Diamond Blackfang and anemia. I believe there's a study that's been going on there in conjunction with NIH. We're going to see some of that data at ASH. I think we learned the ASH abstract, didn't really look to be much in the way of responses, but also looked like these were really difficult patients to treat. just kind of what's your general conclusion? I know we're not going to see the data till next month, but just kind of what are your thoughts around that opportunity specifically?
Yeah, I think the case in DBA and some of these other indications is, you know, the biology is just going to be more complex than it is the EPP. Like EPP, the, you know, the biology translated very clearly from like, you know, PP9 reduction into clinical benefit that we observed in the phase two study. Yeah, it's more complex than some of these other indications. We'll continue to explore, but I think the upshot of this is Bidapertin is, Bidapertin is being, our focus is going to be on EPP.
Okay. maybe you can provide a little bit of just an expectation framework for what we should expect from the RALI MF data that's going to be presented at ASH. So this is now shifting gears to, the antihemoglobin 0974. so I know you've guided to an update. We obviously saw the ASH abstracts. but what should we expect to see within the framework of the presentation itself, just with respect to patient numbers, duration of follow-up, etc.?
Yeah. Yeah. So, I mean, so just as context, you know, at ASH last year, we showed data from the phase one B portion of the study, which was dose finding, for patients with anemia of MF. And anemia of MF is an extremely difficult to treat anemia. And we just saw extraordinary efficacy in the, in the dose finding study. And along the lines of the couple of dimensions that we look, look for in terms of the profile, the magnitude of increase in hemoglobin or reduction in transfusion burden, the durability of that effect, and then how broad that effect is and specifically how the drug works in, you know, patients who are on JAK inhibitors and those who are not.
And I think it's very important that our, for us to be able to show that the drug works together with JAK inhibitors because those will continue to be the mainstay, mainstay of treatment. We were able to show even in the one B study, that the drug was able to hit each of those attributes. And so the goal at ASH, and I think what people are looking for is, you know, now with, you know, now that this is the first, this will be the first data release of, the phase two portion of the study having selected the 50 milligram dose, just seeing those attributes continue to read, continue to persist. and I think, you know, we haven't given guidance in terms of, patient numbers, but the study has recruited well. We expect to have a meaningful group of patients that we can report data on.
And I think, you know, these patients, it'll, it'll be a variety of how it'll be a range of how, how long patients have been on, on, on the drug and that will show data on. But, what we showed at, at EHO was that, you know, some patients had already been on the drug for almost a year. This is from the one B patient. So you should be able, we should be able to have a range of patients from, you know, who have been recently started on the study to who have been on the drug for a very long period of time. And that should give a, give folks a sense for how durable the effect is.
I'll say the last thing that we, plan to show, report on is we said that at EHO, at EHO that we had completed, recruitment of the exploratory cohort of patients who are on mumalotinib. and so that means what, what you can take from that is that we should, we should, we will have data showing how the drug works, not, not only on top of ruxolitinib, but also on top of mumalotinib, one of these newer JAK inhibitors.
So the go forward assumption will be that this will be a drug that can work in a way that's agnostic to JAK inhibitors.
Exactly. I mean, you know, 25,000 patients in the U.S. with MF, almost all those patients are anemic. And the idea is that if you have anemia, we want to, 974 should be the go-to agent, to treat the anemia independent of what your background treatment is.
And then maybe last question related to that presentation, but how should we think about the, the attribution of patients we'll see at ASH as a function of baseline anemia status, right? So are we going to see an overrepresentation of patients who are not transfusion dependent, who are high transfusion burden? Just how are those going to break out across those buckets?
Yeah, I think the, what we showed in the one B is a pretty good representation of that, of that patient set. yeah.
And we, do we know if we're going to be getting the independence data at ASH from Bristol?
we don't know. I didn't see the abstract.
I didn't see the abstract. I'm not sure if it's going to be popping up somewhere there.
Yeah. Yeah. I mean, that was the major development this past year and that, you know, missed its primary endpoint. you know, I think it speaks to, you know, a year ago this was a very, very crowded field. There were approaches targeting, you know, oral small molecule inhibitors targeting ALK2. there was less Padrecept, you know, and now, you know, what we have shown now is that we seem to have a leading profile and the other programs seem to, the competition seem to have, have faded away. So that we're very excited about the program.
What do you think registration looks like here? and I know, I think there's been some commentary before around potentially being able to incorporate all of these different patients in a variety of different anemia states into a single registrational trial. but just curious as to how that works logistically, right? And I guess when I look at what Bristol did with less Padrecept and independence, just kind of knowing that that drug doesn't really work well in patients who have a high transfusion burden at baseline. I don't know if the FDA pushed them to that patient population specifically because they're of the greatest unmet medical need, but just wondering how you're thinking about what a registrational phase three could look like here.
Yeah. Yeah. I mean, it's hard to say exactly what drove the, what specifically drove the independence design. I will say that that segment was the one segment that where less Padrecept performed. It was transfusion dependent patients who were also receiving a JAK inhibitor. That was the best performing segment. My suspicion is that is what drove that study design. because if you look at the segments in their phase two study, less Padrecept just didn't perform, perform as well. from where we are, our expectation is that independent of the patient segment, the drug should be, our drug should be able to have a benefit. So our, our going proposition is still to have a single study, independent of background JAK or, or transfusion status or anemia status, would give us, enable us to have sort of a, a broad label, in NMF.
And I think if you balance the, if you balance the subgroups properly, you should be able to tease out, you know, an anemia signal in a single study. So, you know, you might need to use different endpoints, whether it's hemoglobin in one, in one subgroup or reduction in transfusion burden in a different subgroup, you know, you'll have to sort of design the study that way. But I, we believe it's, it's feasible. as far as what that endpoint is, that's a discussion to be had once we have complete the phase two study, but we're collecting all the classic information that you'd be, all the different, we're collecting a very rich set of data that will inform that, that, that, that discussion at the end of phase two.
Okay. I know another data point of relevance that we just saw was the non-dialysis dependent CKD data for this drug, that was presented at Kidney Week. What would you kind of highlight just as, as the takeaways there and, you know, when might you be in a position to communicate kind of what the status of this program is going forward?
Yeah. I mean, we showed a little bit of the same data from the SAD portion of the study, at ASN last year. so the upshot of what we showed at, at, at, at ASN is that, you know, the drug in a different disease setting, now non-dialysis dependent CKD, continues to do what it's supposed to. It lowers hepcidin, it potentiates iron, and that we also saw early markers of erythropoiesis, that iron is getting into, into red blood cells. the efficacy in terms of hemoglobin readout, however, was a little bit more variable. And what we showed at ASN is we believe that is driven by background levels of EPO, which EPO kind of serves as a multiplier for, for hemoglobin by driving the number of red blood cells.
So I think what that tells us is that the efficacy, the mechanism, you know, is the mechanism of the biology continues to translate extremely well. there's some patient heterogeneity, particularly with regard to background EPO levels, in CKD patients that we need to figure out. And so for the moment, that's what we need to, we need to understand, you know, does it make sense to do a study together with EPO? Does it make sense that we select patients who are high EPO? That's something we need to sort of, define what the next steps forward are. in the meantime, our plan is to continue to take 974 and explore in other, other indications just to understand how the biology works in, in other settings. And, we're planning to initiate an IBD anemia study, sometime early next year.
and so the idea then is to focus 974 on MF and then continue to understand, the biology and some of these other indications. And we're also looking to, bring online the next generation, anti-HCV antibody, which is a longer acting form, which might allow us to be able to, separate some of these indications.
Okay. Can you share your rationale for going after anemia in IBD?
Oh yeah. In these patients, so, anemia is, is a pervasive issue in patients with IBD. It is kind of a classic representation of anemia of inflammation. So the underlying inflammation that drives hepcidin production and that restricts iron. So you have functional iron deficiency. Also, these patients experience blood loss. And so that also contributes to, to anemia. and so supplementing, you know, enhancing, enhancing iron levels should be able to, to help address, address the underlying, underlying anemia. And these patients have normal to high levels of, of, of endogenous EPO production. So we shouldn't run into the same issue that we encounter with CKD.
Okay. maybe you can switch gears to 3405. So as you said before, this is the 10 per 6. I know you're looking at this in polycythemia vera. you're also looking at this in, in, in, in, sickle cell. the PV opportunity for me, I think is very, is very interesting. you know, we follow Insight. I've seen the commercial success of a drug that, you know, has become a billion plus in PV simply because it, it, it causes anemia, right? So, I think there's a lot of opportunity here. The biology has been validated, right? We know that iron restriction is, is, is key to the pathology here. There does appear to be some room for improvement on the safety and dosage fronts, just given what we've seen from the protagonist product profile.
So high level, I guess, what are your thoughts on 3405, the opportunity in PV specifically, and just what kind of competitive edge you think you may have over Rust for Tide?
Yeah. Yeah. I mean, very, very, very well said. And exactly. We're very excited about the opportunity in PV. I think it is a, is a significant market opportunity. And it's very clear that iron restriction is a very important and now well-validated way to be able to treat the condition, you know, not only because, you know, what Rust for Tide has shown is that by iron restriction through hepcidin, that you're able to control hematocrit and avoid phlebotomy, but that patients seem to feel better as well. And this is, that, that's a key, that's a key element. There are limitations to Rust for Tide with regard to the drug, the drug itself. That's a hepcidin memetic, that requires at least once weekly dosing. It seems to be, you know, associated with, you know, injection site reactions.
And, you know, the reason why we, we went after an antibody and going after 10 per 6, which promotes, by doing so, it promotes your body's own production of hepcidin, is that one, it enables more, less frequent dosing. So anywhere, you know, we anticipate we'll be able to get once a month dosing. But it also gave us, you know, what we also showed, at least preclinically and in the healthy volunteer setting is that we had a better quality of what we believe is a better quality of iron restriction. In other words, we're able to see, very significant iron restriction levels and that was durable as well, as opposed to, you know, some of these other approaches. It's a little bit more cyclical.
And, and so we feel that being able to have a, being able to have a controllable, potentially deep iron restriction that's also durable, that mix of, that mix of iron restriction is the, is, is the best way to come up with an agent to be able to restrict iron. So that, that's how we view in, that's how we view the opportunity, in, in PV. And the antibody has been very well behaved so far, that, that we showed in the healthy volunteer study and, you know, looking forward to the phase two readout sometime next year.
Okay. there's also some, some oligos, some siRNAs that are in this, in this space going after the same target. I think CYLINTS has one. IONIS-ONO have one. how do you measure 3405 relative to some of those?
Yeah. I mean, the antibody, our, our antibody, you know, what we showed is we should be able to have durable, durable restriction of iron. I think the other attribute we've always cared a lot about is being able to have, controllable iron restriction as well. Being able to have as much flexibility and gain, you know, being able to balance durability with depth of iron restriction. You know, are you able to get deeper iron restriction without it having, you know, last for too long? We've, we've heard in some from certain treaters that they, they're a little concerned sometimes about having something that is there, is there just such a thing as having too long of iron restriction that you can't back away from that?
So finding that, finding, finding that sort of Goldilocks kind of balance point was important for us as we were thinking about, an agent, an iron restriction agent.
Okay. maybe just a couple more questions. Can you talk about the rationale for this drug in sickle cell disease?
Oh, absolutely. Yeah. So you had mentioned that before. Yeah. So iron restriction, is increasingly, weathered by, is an approach that's been explored in, in sickle cell. The rationale there is, you know, what drives the pathology of sickle, cell disease is the tendency for, hemoglobin S to, to, to polymerize. But, you know, there's very good evidence showing that that tendency to polymerize, which also causes sickling and all the downstream complications, is, occurs at a, at, at a, at a power of 30 of what the concentration of HBS is within the red blood cell. And what folks have shown preclinically and even in clinical setting is that if you can restrict iron, that can actually reduce the concentration of hemoglobin S within the red blood cell and reduce the propensity of the cell to sickle.
And so the problem is there hasn't really been an effective iron restriction agent. Folks have been, you know, required, have been reduced to either using, you know, iron restricted diets or phlebotomy to be able to iron get that, that effect of iron restriction and reducing HBS within the red blood cell. So we're very excited that, you know, we have an agent now that is very controllable that can reduce, that can restrict iron and hopefully that can reduce the HBS within each red blood cell and, you know, reduce the propensity for sickling and also, you know, hemolysis. So this is an exploratory study we, and, that we've initiated and hopefully we'll have some data to share next year.
Okay. Then maybe just lastly, the balance sheet and kind of what that allows you to execute on.
Yeah. I mean, we just completed a financing. So that, you know, we fortified our balance sheet. That should be able to power, power through, some really key milestones for the company. pro forma, we have about $820 million, in our balance, in our balance sheet. That takes us, into 2029. So that should support at a minimum the, commercial, we should be well into the commercialization of Bidapertin, completion of the phase two MF study, completion of the phase two PV study, as well as some of these exploratory studies.
And that guidance doesn't include Bidapertin revenues, correct?
It does not. Yeah.
Nor does it include any PRV voucher sales.
It does not. So it's a very conservative view. Exactly. So this is, yeah, exactly. So we are well capitalized to execute on the next phase of the story.
All right. Jonathan, really appreciate it.
Yeah. Thanks very much, Steve.
Thanks everyone.