Okay. Good afternoon, everyone. Welcome to Guggenheim Healthcare Innovation Conference. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. Our next presenting company is Disc Medicine. We have a few executives from the company here in the room, but I'm going to be chatting here with the Chief Executive Officer, John Quisel. John, why don't you make some opening comments? You and I were just discussing about CNPV, which is also, congratulations on that. Just tell us the Disc story. Obviously, you have a few programs, but what are some of the key things that investors should be focusing on? Then we'll do a Q&A.
Yeah, great. Thanks. It's great to be here. The company, yeah, the big excitement at the moment is our lead program, bitopertin, in a disease called erythropoietic protoporphyria, or EPP for short, was awarded one of the Commissioner's National Priority Vouchers. That review time puts us projecting that we'll be able to get to approval, if all goes well, by the end of this year, early next year, which is an amazing place to be, given that it was about five and a half, six years ago, was our Series A, actually. We were entirely preclinical, actually had not in-licensed bitopertin as a program at that point in time.
Yeah, the history of the company, we were built at that time around looking at controlling iron and heme as fundamental building blocks for red blood cell biology, trying to control the metabolism of iron and heme as a way to manipulate a variety of disorders that arise in the red blood cell compartment. We started off with heme-on type indications, myelofibrosis, polycythemia vera being in target, but all preclinical at that time. Then we became aware of this porphyria disease that arises in the red blood cells and the potential to use bitopertin as a way of controlling heme biosynthesis to diminish the harmful metabolite that builds up in those patients and try to achieve a major clinical response through that mechanism. That is how we built the company. We have been public now since the end of 2022.
This is our third year of trading publicly under the ticker symbol IRON, as you have up there.
Yeah. Very good. Given the acceleration in timeline for bitopertin, number one, just are you seeking for a regular approval, or is this an accelerated approval? I think you're running a confirmatory study, Apollo study, right? What are the expectations? What do you have to produce there?
Yeah. We completed a phase two program in about 100 people and had our end of phase two meeting about a year ago now. At that time, the FDA aligned with a view of putting us on an accelerated approval pathway, which said they're going to use the toxic metabolite, PPIX, as the surrogate endpoint. We would run a confirmatory trial called the Apollo trial, which we aligned on with the FDA and got that going. It was in that context, progressing through about a year of meetings with the FDA around the CMC program, confirmatory trial design, the pre-NDA meeting. We submitted the NDA itself at the end of September, setting up a timeline that would lead to NDA acceptance at the end of November. In that context, the CNPV came in on top of that and really accelerated the projected review time.
Got it. So what preparation now you have to make, given that there is a significant acceleration, right? How are you thinking about the sales force? Where are you on the CMC side, all of that stuff?
Yeah, exactly. Exactly. Key pieces of infrastructure, having drug to launch with, right, the CMC. We have a lot of commercial and clinical batches that are ready to go. The full validation that you typically do would not wrap up until the second quarter of next year. I think there is room to have a discussion with the agency around using the batches that we have in hand, assuming an approval were to come sooner than that. That drug supply foundational piece, number one, having a distributor, having a specialty pharma, those things should all be set up on time. Having reimbursement discussions, those are being significantly compressed. Hiring that team is also compressed. There may be longer prior auth type discussions that happen with the patients coming on with this kind of accelerated launch.
The sales force itself, yeah, that team will probably be seated, but not yet fully trained. Not in the field at the time of launch, which is fine. I think that sets up kind of two phases to the launch here, one where it's kind of the early run, taking the material we have available, making it available. We'll work through the finding patients at key centers or clinical trial rollovers. Then we'll come out with kind of what I'd call the full launch, where we have the sales force seated and the full reimbursement system set up.
Got it. Got it. What will be the size of the sales force?
Yeah. So actually, the job ads are up on our website right now. Twenty-four reps is the team we're looking to see.
Okay. Okay. If the approval comes on time, it seems like would you be able to launch ASAP, or you need, let's say, until the full validation happens in Q2 for you to launch?
We expect the base plan is that we'll be able to launch as soon as the FDA gives the green light. The outside possibility would be Q2 then.
Okay. In terms of the patient population, could you maybe help us understand how many patients have been identified? Who are the easier patients to go and target initially?
Yeah. So the genetics would say there'll be 20,000 people in the U.S. with the genotype. The claims data that we've looked at shows 14,000 people that have been diagnosed using the ICD-10 code for this disease. Of those, we see about 6,000 that we define as engaged patients, meaning they've had more recent EPP care, more frequent EPP care, et cetera. The caregivers for those 6,000 patients, that's who we size the sales force against. We designed the 24 reps to be able to call on the accounts that service those 6,000 highly engaged patients. Reaching the full 14,000 patients will come through long-term sales rep engagement, plus social media strategies, other more kind of broad outreach type approaches. The launch is focused on those 6,000 engaged patients.
Yeah. There is another drug or another device, right, that is approved for it. Can you maybe talk about how that has done? What are the issues with it and how bitopertin is a little bit differentiated on that regard?
Sure. Yeah. There's only one approved therapy for these patients. It's called Scenesse. It works by causing tanning, so providing a barrier against sunlight exposure, which I failed to mention. The main consequence of this disease is extreme sun pain on exposure to sunlight. Scenesse works by tanning. The big impediment there with Scenesse is it requires a surgical implant. A patient has to go into a surgery department, receive an implant under the skin, and then they have to do that every two months to receive that drug. Probably because of that, it's not widely used. We estimate it's about 3% of patients access that therapy. Call it 200-300 patients in any one year might receive that drug.
Got it. What is the number, the price for that?
Yeah. If you receive all six implants across a year, it would come out to about $300,000 on the year.
That is the price for that. Okay. Now for the 6,000 patients, or the 6,000 sort of identified patients that you are building the sales for around, how should we think about the cadence of launch? Because some of these ultra-ultrasound drug launches can be sometimes very rapid or could be very slow. In what spectrum do you or this disease lie, the EPP?
Yeah. I mean, I think when we do our own projections, we're just using other parallel launches in the rare disease space. I think the components that we see in the launch are patients that are already in our clinical trials, meaning rollover patients from the long-term extension, et cetera. There is probably around expected to be 150 or so patients in the trials already.
I see.
We see the top 15 or so centers, essentially our clinical trial sites. There is a substantial number of patients seen by those sites. That is a highly accessible group of patients. You get the remaining top centers that round out that 6,000 patient population.
Got it. Have you talked about the pricing?
No, we haven't. Obviously, we won't set a price until we understand what our label, what the whole package looks like. Like you said, if you look at precedents in the porphyria disease space, you have Scenesse priced at $300,000 a year in EPP. In an adjacent porphyria called hepatic porphyria, Alnylam markets a product called Givlaari priced at $575,000 a year. That gives you a sense of fairly standard rare disease pricing in these indications.
Okay. With regard to the, actually, first on the label, how should we think about the label? Any particular consideration for the label that we need to focus on?
Yeah. I think our preferred label will be a simple one indicated for treating EPP. I think areas where there may be discussion would be the age range. We'll be looking to get a label that goes all the way into the adolescent population. However, that is based on only four adolescent patients in our phase two program. I would say there's substantial reason for some risk around whether I'd be able to get adolescents onto this label. The other question would be, given that this is an approval premised on a surrogate endpoint of PPIX, whether the drug would be labeled for reducing PPIX or would be labeled for just generally treating the disease.
Yeah. Okay. With regard to the confirmatory Apollo study, what are the requirements? When will that study complete and timelines?
Yeah. We started enrolling roughly May of this year. We project about one year to enroll the study. It's 150 patients. We're enrolling in the U.S., Europe, Canada, Australia. We expect about 100 of those patients to come from the U.S., the balance, mostly Europe with a sprinkling in the other territories. We've projected about a year to enroll the study, six months on treatment. Last patient should be out kind of late next year with the data following a month or two after that. That's the basic attributes of the trial. The endpoints, coprimary PP9 reduction, which we've proven kind of inarguably in the phase two program, and then a measure of time and light at the end of the six-month trial period.
Got it. Got it. Very good. All right. Moving on to the next asset, 0974. Can you maybe describe the mechanism for us and the areas that you're going with?
Yeah, sure. So it's a monoclonal antibody against a genetically defined target called hemojuvelin, which is a core regulator of iron in the body, right? There are actually humans who have loss of function mutations in hemojuvelin. The phenotype is a kind of florid iron availability in the blood, which in a normal person is not particularly helpful for anything. In many kinds of anemia, actually, the anemia is caused by restriction of iron inside the body. By targeting hemojuvelin, we expect to, and have shown now in the clinic, that we release that restricted iron situation and release iron from internal stores into the blood, where it can be used by the bone marrow to produce new red blood cells. I think it's axiomatic that iron is one of the key building blocks of red blood cells. That's the way it works.
It's a monoclonal antibody delivered once every four weeks, 50 mg fixed dose. We did a healthy volunteer study where we showed very nice pharmacokinetics, pharmacodynamics, suppressing the target called hepcidin, mobilizing iron in the blood. And actually, even the healthy volunteers saw an improved hemoglobin profile. The target is overall anemia of inflammation. It's a set of anemias driven by inflammatory disease, which is what causes the trapping of iron inside the body. Our lead indication is myelofibrosis, which is a very severe hem-onc kind of anemia marked by a very high degree of inflammation. As a result, there was a hypothesis, I think first generated at the Mayo Clinic, that this inflammation may be leading to iron-restricted red blood cell production and that by releasing that, you may have a productive effect. There's actually no therapy approved to treat anemia in myelofibrosis patients.
If we're successful with this program, and the data have been very good so far, we'd be the first and really only drug approved for these patients.
You've done a phase Ib, right, where you had shown some data also in patients that were on JAK. Can you just review those data for us? What exactly are you able to achieve in those patients?
Yeah, sure. We presented phase Ib data to about 35 patients across a variety of different dose levels. That was at ASH last year in December. We saw very good response rates across the board. The FDA advised us to look at the patients in three groups, those who are not transfused at all. This is looking at the 12-weeks predosing, those who are receiving one to two units of transfusion. That is the low transfusion burden group. Then those with three-plus units transfused. That would be the high transfusion burden group.
Across all those groups, we showed a very good response rate, about 50% in the non-transfused patients, about 80% in the low transfusion burden group, and about 40% in the high transfusion burden group, all of those being well above the target you'd want to see in order to feel that you have an effective therapy in a program that can progress into a pivotal trial. What we're doing now is looking in a 90-patient group study called the RALI-MF trial, where we've chosen a single dose now, the 50 mg dose, which appeared to be the best, kind of the lowest high efficacy group. We'll be reading out an interim look at that at ASH this year, coming in about a month now.
Yeah. A few weeks. Yeah. What would be, so in the RALI-MF study, are you enrolling patients in all those three subtypes?
Yes, exactly.
What are the benchmarks? What exactly would you like to show in those three subtypes as an interim readout?
Yeah, yeah. I think 30% across the board is the bar. Maybe it's a little higher for that low transfusion burden cohort that the endpoint seems a bit less stringent. Call it 30, 50, 30. We're looking to see. Again, we're sitting looking at phase Ib data at 50, 80, 40. We feel like we're in great shape to clear that bar.
Got it. Are there any biomarker at baseline that you could see to identify these patients?
Yeah. To identify the best responders.
The best responders, yeah.
No. Yeah. We haven't really been able to identify a biomarker. We've learned that baseline EPO is very important in predicting responses to our drug. In myelofibrosis, essentially every patient has a very high EPO level. That hasn't been a distinguishing feature.
Correct. Yeah. Are these patients on JAK?
Yeah. Many of them are. Our trial is designed to be all-comers. We have patients on Jakafi. We have patients on Ojjaara or Momelotinib. What we showed last year is a very good response rate on people on Jakafi, which is clinically important because one of the side effects of that drug, which is probably the best therapy for MF patients, is that it causes anemia. Having a drug that can help manage that anemia in combination is a really attractive profile. It looks like we're achieving that.
Yeah. If you hit your threshold of 30, 50, 30, let's say in these three subtypes, which subtype are you going to go for in the pivotal? I think I assume it's going to be a separate path for NTD versus transfusion dependent.
Oh, our goal is to have one single pivotal trial that aggregates all the patients who are likely to respond. I think actually I would view the non-transfused and the low transfusion burden patients as being one group.
One group. Correct.
Because they're not physiologically very different. Highly transfused, that's a relatively rare group of patients. They've typically received a lot of transfusion, which actually ends up loading a fair amount of iron into the patients. They may have a different attribute.
Okay. Okay. So the next step will be just pivotal after this data and interim?
Yeah. I mean, we'll get this data then next year. We haven't guided when exactly we'll have the final data, an end of phase two meeting with the FDA, and then that'll progress to a phase three trial.
Got it. Are there other indications you're pursuing with 974?
There are. We looked in chronic kidney disease, the non-dialysis populations. That data actually just came out over this weekend, patchy, not overwhelming success there. Intriguingly, what we saw is the high EPO baseline patients were the responders, which probably helps explain why we've had such great responses in the MF population.
I see.
We're also about to start early next year a study in patients who have anemia as a consequence of inflammatory bowel disease, who are also interestingly probably a high baseline EPO population. We think the drug will be applicable across this wide range of anemia of inflammation patients. I think the first effort now that we really have a good signal coming in myelofibrosis is to focus there, drive towards approval on that indication. We have a second-generation antibody with a longer half-life that we will probably use to carry much of the weight of development in some of these larger indications.
Yeah. So you'll see CKD, yeah. Okay. What about the third asset?
Yeah. Third asset, very exciting, polycythemia vera.
Yeah, PV.
The premise here is actually to achieve iron restriction. This has been proven out by Rusfertide, a program at Protagonist and Takeda. Really nice data, at least in the top-line press release. Our goal here is to provide something that is given a more patient-friendly presentation, kind of Q4 weeks, hopefully with a better safety profile. We think the biology has already been largely proven out. We are in phase two now, hoping to enroll that rapidly, get some data next year, and then progress to a pivotal trial as quickly as we can.
Okay. Any particular bar for the phase two study that you're reading out next year?
Yeah. A key readout is to look at achieving target hematocrit of 45% without needing a phlebotomy.
I see.
Now, Rusfertide achieved about 75% on that, which is very good data. So our goal is to get close to that.
Close to that. Okay. A lot going on between the commercial prep and the two big programs on the heme side.
Yeah. It's very busy.
Very busy. Okay. How are the financials?
Yeah. The financials are great. We ended quarter two, sorry, quarter three, with around $610 million on hand, maybe off by plus or minus. And then we raised another $211 million net in a stock offering after the CNPV announcement. So we're sitting at around $826 million or so in terms of pro forma cash on hand. The runway for that is early 2029. And in that runway, we're taking no revenue for bitopertin. So it's a very conservative runway statement.
Yeah. Have you articulated in terms of how big bitopertin could be from market? What is your?
Yeah. I mean, look, if you look at the analyst forecasts, it's $800 million peak to $1.4 billion or so. I think there's a huge opportunity here. We're excited about it. If you think about it, 14,000 U.S. patients with rare disease pricing. If we're able to actually fully access that and bring this drug to all those patients, it's a pretty big rare disease market along the lines of what you see in HAE or PNH.
Got it. Very good. I think that's all I had for you.
Yeah. Great.
Thank you so much for your time.
Thank you.
Appreciate it.
Appreciate it.
Thank you.