Welcome, everyone, to Jeffrey's 2026 Global Healthcare Conference. My name is Roger Song, senior, and this covers Micah Biotech. It is my pleasure to have the fireside chat with our next company, Disco Medicine, and then we have a CEO, John Krithal.

Thanks, Roger. Great to be here.

Alrighty, so before we dive into the questions, why not you give us some high-level overview of Disco, where you are right now, and then also a little bit forward-looking and what we should expect for the rest of the year, in the coming years.

Right. So we're at a very exciting moment of the company, headed towards the end of the year, where our lead program, Bidapurton, will read out from its Phase III trial. So that's obviously a highly anticipated event. Then we have two Phase II programs in progress. The second one is in the anemia of myelofibrosis. Just had an oral presentation of ASCO with some really exciting interim data and expect to have a readout from our end of Phase II meeting with the FDA. later this year. Progress that program to phase three next year and then the third program in polycythemia vera where we expect to have our first phase two proof of concept data by the end of the year and you know if that all goes well could also be progressing to phase three next year. So they kind of step forward as we come into the second half of the year.

Awesome all right so we have a lot to talk about today and then maybe we uh since we just Just right after the ASCO, why don't you give us some highlights of the ASCO data from the fibrosis, myelofibrosis anemia. So in this thing, it is a little bit more recent data cuts and a little bit more patients. And then what are the methods there and anything change on the profile before you can have the end of phase two meeting?

Right, yeah. So there's very severe anemia in these myelofibrosis patients. There is no drug approved to manage that, and really none in development other than DISCO-974 at this point. And the data we showed at ASH last year already looked very promising. We've broken the patients into three categories based on their baseline transfusion levels. So about 50% to 60% of these patients will be so-called non-transfusion dependent, meaning there are no transfusions during the baseline 12-week period. Then we have the low transfusion burden, where there's one or two units transfused during that baseline period, and the high transfusion, which is three units or more. So at ASH last year, we showed great, you know, unprecedented good response rates in the non-transfused and the low transfusion burden patients, but quite unclear in the high transfusion burden group. Now at ASCO, and actually a similar presentation coming at the European Hematology Association, in just a week or so. We're showing great responses across all three categories of patients. And then the other important message is that, and important data, is that, you know, about more than half of these patients are being treated with a JAK inhibitor to manage spleen size and symptoms. And one question is whether the drug would work on top of those JAK inhibitors, which do affect erythropoiesis. And the answer is unambiguously, the drug clearly works in combination with essentially any of the JAK inhibitors that these patients might be on. So I think the message now, very clearly, and this is how we're planning for our end of phase two meeting and our phase three trial design now, the drug is working essentially for anyone who's anemic with myelofibrosis. And so we're designing a trial program that should address all of these patients and try to make the drug available to address anemia in the maximum number of patients possible.

Yeah. Great. And then I think last ASH, so the transfusion-dependent high population, you have fewer patients and then shorter duration, and then this time you have more patients, and it seems the response rate also going pretty close to what other subgroup is hearing. So that's probably the key message here.

They're all responding. All these subgroups are getting response rates in the 50% to 60% rate. So it just looks really consistent, which makes us feel more comfortable about the data Yeah, got it.

And then in terms of the EHA coming week, would that be the same data cuts or you will have some other?

Yeah, the main kind of body, the main figures will be, you know, the same data. There may be some additional analyses that we provide. But, yeah, basically the same aspects.

So, and then later this year, you're going to give us the full Phase II data readout, the data set, and then you're going to talk with the FDA by the end of the year for the end of phase two meeting. So I believe you designed the study, you know, 30 patients per cohort. Do you expect to get a full enrollment by the time and give us the data with the sufficient follow-up six months or maybe some of the, you know, depends on the enrollment, you don't need a full data set before you have the conversation?

Yeah, I mean, so one of the learnings was that the number of high transfusion burden patients and really transfused patients overall has been decreasing due to just improved management so those cohorts enrolled slower than expected we've actually ended up opening some additional sites to try to round out that enrollment meanwhile the non-transfuse patients enrolled very rapidly and represent as i said the majority of patients so that cohort the non-transfuse is closed at this point the others were still completing So as we come into the end of the year, you know, each year we typically submit abstracts to ASH. We typically are accepted and have a presentation there. I think that cadence should continue. What's different this year is now we feel like we've got the critical mass of data to go have it in a Phase II meeting with the FDA. So I think there will be one more data cut that will then be used to form the basis for our Phase III proposal to the FDA. We're anticipating that end of phase two meeting to happen somewhere near the end of the year, hopefully, but no guarantee. It can come such that we're able to share the output from that meeting roughly around the time of ASH as well. And then the presentation we'd have at ASH would probably be that exact same data cut. So it may not be the full top line data, but it would be whatever we took to the regulators for the end of phase two discussion.

Got it. Okay. All right, You have a sequence of the data released before the year, and that's good. And then in terms of the end of phase two meeting, the phase three pivotal design, understand some of the subpopulation, you have a more defined regulatory kind of path. Some of them are you maybe still need to discuss with the FDA. But I do notice outside of the transfusion or the hemoglobin endpoint, you also have some PRO and the fatigue score, which are, you know, training towards the right direction.

So how should we think about among those three subgroups, and then what is the more certain registration path versus the other ones, and what's your approach to get to the period Yeah, it appears generally precedented that if a patient has a transfusion rate at baseline, you can use some kind of transfusion-based endpoint for an approval endpoint, and typically it's so-called transfusion independence, which means for some period of time, either 12 weeks, 16 weeks, 24 weeks, you make them transfusion-free. You count the responders, and if you're stat-sig over placebo on your response rate, that can form the basis for approval in a transfused population. In a non-transfused population, typically, you know, the FDA doesn't allow you to use a transfusion base rate basis so hemoglobin is the most reliable metric but they also don't allow you outside the u.s. typically you can get approval on hemoglobin inside the u.s. you need to add you know augment that was something that's viewed as clinically meaningful and in that domain you know actually just recently agios had a study in beta thal where they broke it into two studies that non-transfused and the transfused use the transfusion independence for the transfused and in the non-transfused population used a hemoglobin primary with a fatigue score as the secondary and that's a reasonably common approach in anemias because one of the obvious and easily measured clinical consequences of anemia is fatigue and that's why you'll see in our ASCO and EHOP presentations we're showing fatigue score data that looks quite good. In fact, even correlates with the hemoglobin increase. So we feel good that that could be the way we design our phase three program for the non-transfused population. We're also scoring well on other PROs. Remarkably, the so-called total symptom score, 50% responder analysis, we're hitting on that almost as well as JAK inhibitors, which is where that score was designed for. So we have a lot of options about how we want to kind of demonstrate clinical benefit in the non-transfused population and we'll kind of finalize that after the end of phase two meeting.

Got it.

And then you do expect you can get alignment with the FDA among all of those three subpopulation or if you have anything you know some work to be done with the FDA you can start with some of the subgroup you know in parallel or you know in sequence in terms of the phase three studies. yeah that's right I mean the goal is to present the whole program and ideally we get alignment on the whole on both you know on the whole protocol system in that one end of phase two meeting and be able to start both those trials simultaneously you know next year or you know hopefully early next year but you know you can't rule out that they might have more questions about one population than another and there could be some staggering it's hard to know hard to predict until you get there.

Yeah. But at least I think it's totally possible you can get a pivotal star with certain subpopulation and then even get approval even if the other subpopulation may not.

Yeah. Yeah. I mean, this is rare disease.

So if, for example, we end up doing two studies, each one would presumably support a label for that population by itself without, you know, it's not it's not a situation we need two studies to support approval okay got it okay great before we move on to the you know burden for the EPP and then the for the anemia or 79 0974 you have other indication also planned right and then you know IBD and then etc so CKD you already have some data earlier not last year so among all the indications how what's the soft process to prioritize or do you think about the lack of success for those indication expansion?

Right. So the way the drug works, it's really addressing what's called the anemia of inflammation or anemia of chronic disease. So if you look across the landscape, myelofibrosis is a very good archetype of that, and that's probably why the drug works so well there. We probed chronic kidney disease with mixed results, And what we learned from that is the endogenous EPO level that patients have influences their response to our product. So in patients with chronic kidney disease, you get heterogeneity. Some patients have relatively low endogenous EPO levels, and those tended to be poor responders. So now when we think about indications where the drug could be used, it would be anemia of inflammation accompanied by relatively high EPO levels. And that actually is pretty much most kinds of anemia. Your body is responding to that by pushing EPO production. But because iron is limited, the body can't really make the red cells. And so then our drug can make that iron available, and you get a good response. So IBD, as you referenced too, that's a disease where there's definitely inflammation. Patient groups are very concerned about fatigue. And we've got that study going now. And they tend to have high EPO levels. So I think, you know, beyond that, it would be probably thinking about just baskets of patients who have anemia of chronic disease or inflammatory disease and looking for those who, you know, would benefit from anemia therapy.

Interesting. So IBD, I know you have a separate cohort. You are running trial, and then when are we going to see the data for IBD?

We should have some initial data by early next year. Early next year.

And then you think the next you will potentially do some kind of basket trial, and then you're going to just, you know, in terms of the patient enrollment, everyone, you know, patient with the inflammatory disease and anemia with relatively high EPO, that's the inclusion criteria?

That would be ideal. It is still an idea. That's not one that we've really, you know, tested with sites yet, but I think it's precedented in this field that you wouldn't typically continue to do indication after indication after indication. At some point, you'd say, this biology is pretty consistent. Let's just do a basket-type trial.

Yeah, okay. Yeah, I think, you know, ONSM4, we really like the mechanism, and then also the data so far for MF is pretty strong. And then, you know, a lot of the expansion opportunity. But I understand the investors focus still bit a bit old because it's a more near-term capital study, and then you just get a CMPV, the CLL, recent. And I think the next step is you are having the type A meeting with the FDA, reaffirm the ongoing Apollo trial is supportive of the approval. Is that the next step?

That is correct, yeah. So there's an NFA, sorry, a type A meeting that you get as a matter of right after a CRL. And then when, you know, we'll need to wait 30 days after that meeting to get the minutes, at which point then we can talk about the results with with the public I would say our expectation around that meeting is pretty neutral meaning there's all kinds of things we could talk about in terms of is there room to reverse the CRL to get approval without the phase 3 data also just to confirm that the phase 3 data should be satisfying and you know drives a traditional approval path but But the truth is, I think all that is already baked. I think there's really, because the data is so close, there's no room to reverse the CRL. And, but also we've had longstanding alignment with the FDA around the design of that program. And even if you read the CRL, you can see that they're basically saying, okay, accelerated approval, we don't think you've shown us the evidence to support that. But if you show us the full phase three readout, that would be the basis for a traditional approval.

So that's the path we're on. got it uh just to confirm a clarify have you had a meeting already or we can't say okay okay so either we haven't had it or we've had it and we're waiting 30 days for the minutes okay all right good so you say enough so you know you have your uh disclosure obligation there okay got it so um all right so that's a kind of a uh de-risking but also the base case should be uh people not expecting too much surprise that's a you know public that is the base case that's right okay got it all right so and then uh you're running up apollo you will have the data readout later this year um you know just to walk us through in terms of the translation from your phase two to phase three you know because initially people think okay you can't get approval and then this is become a i don't know it's kind of bonus trial and now it's more critical in terms of people want a handicapped before the data readout how subjective that endpoint you have for the primary endpoint and how confident you are for the translation from phase two to phase two because phase two is positive yeah yeah you know we're very confident we we ran a good phase two program with a hundred patients we saw very consistent reductions in protoporphyr 9 and we saw improvements across every clinical endpoint that we measured pretty much some of them were stat-sig, some not.

None of them powered. So we got a very good view of the variability, notably an endpoint called the total time in sunlight had a significant placebo effect in the first two months of that. That would be the precedent endpoint for getting approval for the one drug that's approved in this disease. So we decided to modify that endpoint based on those phase two learnings to just look at the time in light in the month six after the placebo effect has waned. Otherwise, and by the way, had we measured that as the endpoint in phase two, it would have been, you know, would have been, you know, stat sig post hoc. So we used all of that learning from variability, et cetera, to design and power the phase three trial. You know, every other respect we maintained the phase three the the phase two elements of the trial exactly in phase three right so the goal was to kind of keep the biology exactly the same and simply treat it as a math problem with adequate powering for phase three so we moved from being you know 25 patients per arm we chose our best dose the 60 milligram dose to now 75 patients per arm so effectively tripled the study size and then due to you know excessive demand at sites which you know we're flattered to have patients really want access to this drug we ended up over enrolling you know enrolling up to 183 patients so now we have 90 per group versus phase two where we had only 25 per group and we feel very good about the powering and we've had a chance to look at a blinded sample size reassessment with 50 completers we were able to tell to assess the variability, and that matched very well with the variability that was seen in phase two. So all the assumptions that went into that phase three trial design are bearing out very well so far.

Got it. Okay. And then, you know, with a little bit upsized of sample size and also the design from phase two, phase three, that's the confidence coming from. And then the other angle is the recent Tanabe, they reported a positive phase three top line. Then later we see from the AAD, they gave us detailed data from their drug. So that's another kind of a validation, but also we want to highlight the endpoint is slightly different. So how we should think about the risk through from their trial, probably it's mostly on the placebo arm and how the patient will behave in this disease, but using slightly different Yeah, well, I mean, I think their trial shows what we already knew is you can win on these time and light endpoints, right?

People worry about the subjectivity, the variability, but it can be measured. And, you know, we saw numerical and some stat sig benefit differences in phase two, and it's really just a powering question to turn that into stat sig for phase three. So I think, you know, they showed that similarly that you can do that. But in terms of, you know, interestingly, the one approved products in S, this program, Drisomeligon, our program, Bidapurton, we're all using slightly different ways of measuring the degree to which patients spend time in light. We're all on this quest because the FDA has told us to. This is what they want. This is what they seem to think is clinically meaningful. um so it makes it a little bit more difficult to compare across programs but you know roughly speaking if you look at the the one approved product they had about a 50 increase in their metric of light time in light uh relative to placebo uh we showed at the end of our phase two trial about a doubling and uh dursum elegan the oral tanning agent showed close to a doubling as well. So I think, you know, that gives you a feel for the time and light endpoints. Interestingly, you know, if our phase two data bear out in phase three, we would seem to have a much more profound effect on phototoxic reactions. But, you know, we need to prove that out in the phase three trial.

Yeah. So SNAS is an implant. We know it's not that convenient, but the smelagom, which is the oral version of the SNAS. And so how should we think about, know both of you are oral but you know on one side if your efficacy is better no they can be a be preferred maybe on the safety side and they also found a mechanism side so why you think for a bit of burden what kind of the the profile can win the market and to get more market share compared to that does medical yeah I mean our approach is going to the root cause of the disease which is a toxic metabolite called protoporphyrin 9 that builds up as a consequence of a genetic mutation in the heme biosynthetic pathway.

So the entire disease, the light sensitivity, the liver damage, all comes from the buildup of PP9 in the body. And our drug directly reduces that buildup. And that's unique. We're the only people with that kind of effect. and we believe that that will both result in a reduction in the sunlight damage but it also you know one of the scary complications is this potentially fatal complications of the disease is liver failure due to crystals of PP9 precipitating in the hepatobiliary system and we've you know shown in mouse data that this mechanism by reducing PP9 you do greatly decrease that liver damage and the epidemiology would say that people with less PP9 in their bodies have less of this kind of liver damage buildup so we when we now we're not able to study that in this program but you know eventually we will run some clinical trials that look directly at liver damage in patients who are experiencing that but the expectation is that by reducing PP9 you would have a holistic benefit on every aspect of the disease and that's going to be distinct from the way these tanning mechanisms work. Yeah.

Yeah, I think that, you know, I would treat a bit as the, you know, disease modifying because you're talking the root cause of the disease. And then one clarification, maybe also confusion from investor is the PP9 in Hobula level or the plasma level because we know another company is also targeting PP9 but seems they're only targeting one compartment of the PP9, not the Hobula.

Yeah, so, I mean, essentially all the PP9 that builds up in your body is in the blood, right? Then from there it gets cleared through the liver and out. And in the blood, about 90% of it is in the red blood cells and about 10% is in the plasma. So we're measuring the whole blood. That's what's typically been measured. That or it doesn't really make much difference, right? The cellular compartment, 90%, the whole blood, 100%. If you want to measure the plasma compartment, which, yeah, we have one competitor. working on that that's quite distinct it's a very volatile component you know compartment and the you know clinical meaning of doing that has not really been established yet but you know our approach has been again to kind of reduce the PP9 that builds up in the in the blood which is you know essentially reflecting that we're reducing the whole body PP9 levels yeah okay yeah I like that approach you know you address the whole PP9 versus you know you sequence the PP9 in the plasma, but the question is what if you stop dosing or you have an issue,

you know, release the PP9 from the other compartment and they will call in the issue continue.

Right, sure.

Okay, good. And then now we have a pivotal data lining up for the fourth quarter later this year and then approval, you know, submission next year. So how should we think about the pre-commercial activity, understanding you were accelerating that because you were under CNPV. Now you're kind of relaxed a little bit, but I don't believe you are slowing down anyway.

Yeah, I mean, we're certainly, we have PTSD from, you know, this kind of run into the CNPV, you know, hired a full team to go launch the drug. Very sadly, had to lay off a portion of that team. We did retain a small sales team and an MSL team who are able to go out and call on accounts. We have claims data suggesting 14,000 patients. And that claims data comes with physicians who are providing care to these patients. so the goal is to have the reps go visit those accounts you know build a relationship start to understand are the patients really there you know is the claims data telling us the truth or they may be getting their care elsewhere and tracking down you know so essentially mapping the world of of EPP patients and where their care is happening and in the process hoping to raise awareness of the disease you know despite the fact that there is one approved product you know there's probably more patients in clinical trials than there are on that product so it's a very undeveloped market overall and therefore the importance of having people out there as well as the advocacy groups out there raising awareness of the disease so that when a product does become available we can quickly turn the switch and have doctors you know alerting their patients to new therapeutic options that come along.

Yeah, you know, honestly, when you had, you're in the CMPV, honestly, we are a little bit worried about the early launch because you're not fully ready, right? So you're not even having the full sales team. Now it's kind of opposite. You have a lot of time, but when are we going to start, you're going to start to rebuild the sales team and then get ready, you know, how we should think about the early launch if they're going to get approval next year?

Well, we will certainly be ready. I mean, we were ready in practice as of February, and then now we have a lot of time to really understand this much better. And so we'll, based on the data, we generate, kind of recalculate our launch team needs. You know, how many reps do we really need, given the distribution of patients and the number of counts they need to call on. And I think we'll be well prepared. And it's already apparent that there's, you know, quite a bit of concentration of patients at top centers and then quite a bit of dispersity, you know, quite diffuse outside of that. So I think that makes kind of the near-term launch relatively straightforward. And then long-term, the challenge is creating awareness of treatment options for patients who probably in large part have given up hope, right, because they got their diagnosis. They found out there wasn't much to do for it, and they've kind of ceased to get medical care. We need to try to figure out how to make them aware and provide the care that they can get now.

I hope your sales team is not PTSD, and then they're willing to come back, and then when you're ready.

I mean, it's unbelievably motivating to try to treat these patients. There are all these anecdotes out there in the media now because the patient groups were really frustrated about the CRL and really wanted this drug to be available, and I think they became much more active. and if you read these accounts it's truly moving I mean people just the way their lives have changed is it's you know for those of us working on the product it's motivating and I can tell you the sales teams feel that same motivation okay all right our time is up and thank you so much John and thank you for everyone okay thank you