Disc Medicine, Inc. (IRON) September 2026 Conference Transcript

All right. Good morning, everybody. I think we'll get started here with the first fireside this morning. My name is Derek Archilla. I'm one of the senior biotech analysts here at Wells Fargo. Very excited to be joined by Dysmedicine with John Kweisel, CEO. John, great to have you here. Great to be here. Excellent. Well, you know, timely because we've got some, you know, hot news for Dys3405 and some data in PV that you guys just presented at the Soho conference. So maybe that's a good place to start in terms of just, you know, updating us on that program.

Yeah, it's a great place to start. So DISC-3405 is a monoclonal antibody against TEMPOR-S6 designed to restrict iron, which is a mechanism that has already been proven out to be effective in managing excess red blood cell production in polycythemia vera patients. And what's been exciting about this program is just the rapid progress. We honestly, our guidance was that we wouldn't have data until the end of the year, but the trial enrolled far ahead of schedule and so we were able to pull in or really needed to pull in our initial data disclosure. So trial is two cohorts, cohort A, cohort B. Cohort A is designed to probe essentially our max dose Q2 weeks dosing but there's a dose run-in kind of adjustment just checking that we've got the right dose for these patients at the beginning of the trial and the data just shows a complete snapshot of all the cohort patient cohort A patients that we have on board as of the data cutoff back in the summer, and it looks really promising. I think as our first experience in these patients, we can see for sure, as expected, the drug is restricting iron, engaging all the mechanisms that are supposed to be engaged, and the real goal here is to achieve really the most kind of side effect-free control of hematocrit that you can achieve for these patients. That's really the objective. And it is a competitive space. And I think we expect all of these iron restriction agents to end up with about the same efficacy level. And that's assessed by looking at the rate of phlebotomy. So typically these patients are being managed by simply bloodletting, which it turns out makes them feel miserable. And so the idea of replacing that with the drug that allows people to keep their iron in their bodies, which makes them feel a lot better, no surprise, but still retain that kind of stable hematocrit around 45%. That's the objective. So we've seen recent approval of Rusfertide, which is the pioneering product in this space, showing about 70% to 80% phlebotomy-free, reduction in phlebotomy rate. And that's pretty much exactly what we see. We see a reduction in the phlebotomy rate from about four per unit of time down to about 0.6, which is right in the same neighborhood as we've seen with other agents. If you look at the rate at which patients from time zero are phlebotomy free, that's a little bit north of 60%. Now that's a little low compared to the comparators, but the the relevant apples to apples actually look once you're on a stable dose that's been maintained for a while. And there we had about nine patients who'd been on long enough to to achieve that, and seven of those nine were phlebotomy free as well during that kind of later stable dose interval, and that puts us in the high 70% range for phlebotomy free, which is right in amongst all the other compounds with the iron restriction mechanism. So, and side effect wise, we see almost no anemia, almost no injection site reaction, and I think that is, if we're able to prove that out in a larger set of data, that is actually distinct from, I think, what some of the other agents have been able to show. Because sometimes you get anemia, apparently, as you, you know, if you restrict iron too much or too long, it pushes down too hard on hematocrit. And we believe that with the only antibody being developed here, we'll be able to achieve a kind of a tailored effect on iron and hematocrit that may be able to give patients, you know, really clean experience.

So what is the biggest unmet need in this indication? Is it around kind of safety or is it that most of the efficacy is kind of, you know, generally in the same ballpark? So what are we solving for here?

Yeah, I mean, I think you want to achieve, you know, clearly everyone can achieve a very significant effect on hematocrit with this mechanism, which is no surprise given the power that iron has on erythropoiesis and even some evidence of kind of direct interaction with the JAK pathways that tend to be hyperactive in this disease. So no surprise that all these agents are able to achieve that kind of a similar level of efficacy. And so I think then really it just becomes about giving the best possible product experience for the patients, which is a mix of ease and convenience, you know, and avoidance of any side effects. So if you look across the landscape, there's some evidence of injection site reactions of some agents, some anemia with other agents. And so I think those have been the places where different molecules may be able to distinguish themselves.

Gotcha. So I guess what's next for this program in terms of development? It seems like now we've got good proof of mechanism, proof of biology. So where to next and what's kind of the path to registration?

Yeah. So the trial fully enrolled to 20 patient cohorts, which are designed to kind of probe the Q2 weeks dosing regimen, Q4 weeks dosing. That'll come in cohort B. That was fully enrolled by the middle of the summer. And so we'll be able to have data from cohort B by the end of the year. and from there on the you know the trial will wrap up and I think our plan is to move to an end of phase two meeting get that going into phase three and you know with gratitude to the to the rust for tide program that came before us I think the pathway has been pretty well established in terms of what a trial looks like what the endpoints are going to look like so somewhat different for us where everything else we're doing is kind of breaking open new new ground there's there's a pretty well established path here and we think we can move fast.

Gotcha. Do you think you need Q4 to, you know, Q4W, like, dosing to win in this market? Or is this kind of just more of a nice to have?

Well, you know, our competition on the Temporus 6 target is nucleic acids. One of them is being explored in Q4. One of them is going to be explored at Q12. So, you know, I think the longer, the better, perhaps, but I would prioritize safety, and I think actually avoiding anemia is part of the charm of the antibody approach. And so I think either one could be competitive, especially given that in the end, as a commercial presentation, our goal is, of course, to get to an auto-injector, self-administered approach that's very straightforward for patients to use. I think once you're in that kind of product presentation, Q2, Q4 weeks, doesn't really matter very much. Gotcha.

And I guess as you think about, you know, the kind of the competitive intensity as you've been talking about, where do you see, you know, 3405 kind of fitting in in the treatment paradigm? Is this first line or is this kind of like after failures? And I guess what was the patient makeup, you know, within the first cohort here?

Yeah, yeah, that's actually part of the data that's pretty interesting. We, you know, as a first trial, we're very open to patients on all kinds of different therapies. And as a result, you can see we have patients on hydroxyurea, which is the mainstay front line therapy. You have patients on interferon, which is a little bit more of an aggressive therapy. And, you know, clearly the iron restriction effect is working on top of any of those. I think the goal would be to have this be a frontline approach. I mean, honestly, if you're looking to control hematocrit, avoid thromboembolic events, I would hope that eventually we're maybe even able to displace hydroxyurea as the first therapy of choice because I think iron restriction as a category may show some real safety advantages relative to that molecule. So, you know, I think that's the goal. It's a chronic disease for these patients. So you really want something that's straightforward, relatively free of side effects that they can take for a long time, just keep that thromboembolic risk under control. And then I think some of these other agents like interferons and JAK inhibitors tend to be reserved for the more, you know, the most severe patients who are perhaps threatening to transition to a myelofibrosis or later stage disease.

How do you view this commercial opportunity relative to some of the other programs in I think it's the biggest yet.

I mean, it is the most competitive, so you could divide the market amongst the competitors. But as a market, I think it's probably underappreciated. I think we've seen some evidence of where rust for tide has been priced, which is, I I guess I'll just roughly approximate it as it seems like it's going to be in the same zone as Lospatercept, you know, treating anemia, low hemoglobin in the MDS space. PV is probably similarly sized to MDS, right, talking 150,000 patients in the U.S., 50,000 to 100,000 of those probably being managed by phlebotomy. And I think the data that Russ Retide showed in phase three would indicate that probably all those patients ought to be moved off phlebotomy onto an iron restricting drug to help them really feel a lot better as they move through the disease and live with it and so if you can accomplish all that it creates really a very large market gosh I mean in terms of what you just talked about the patients being managed by phlebotomy is that kind of the low-hanging fruit and then you can move to patients who are not being managed that way or I guess how do you think about you know I mean I think you know phlebotomy is really there to create iron deprivation in the patients and what these drugs do is create iron restriction in the red blood cell compartment but allows the body to not be deprived of iron. So the easiest therapeutic rationale is to simply replace phlebotomy. I think you know replacing hydroxyurea I mean I think a lot of patients frankly are being once you're a high-risk patient often being managed by both right and probably initially you just simply sub out the phlebotomy put in the iron restriction but eventually you know perhaps people will experiment with just going purely with the iron restriction gotcha and so you know you kind of outlined the path here in terms of you know end of phase two and then a pretty well you know established you know regulatory path for for approval so it seems like there's not a lot of things there I mean is Is there anything to learn from this data set that you can kind of apply to other indications

that you'd pursue with 3405?

Oh, that's interesting. Well, we do have a trial open in sickle cell disease, a very different disease, but very similar hypothesis, which is, I think, relatively underappreciated, is that there's a growing trend in sickle cell to actually try to manage patients by phlebotomy. And it's the same idea of restricting iron, actually reducing the amount of sickling hemoglobin that builds up in each cell. And phlebotomy has shown pretty good effects clinically. So, you know, I think what we are learning is that you can definitely, you know, if there's a disease that's being managed by phlebotomy, it's pretty well understood now that that is going to cause patients to feel bad. because the point of that approach is to induce a whole body iron deprivation and thereby force iron restriction on the red cell compartment and this approach that we're taking allows us to just restrict it in the red cell compartment let your body keep its iron feel okay your brain needs iron to help you think straight and so I think seeing that perform well with the with so far are a good safety profile suggests that these targets can work as well in sickle cell. But that is a more complex disease that we'll have to work through carefully. But we should have some data on that, actually, by the end of this year, also. More case report data. It's a slower moving trial, but very interesting.

How many patients do you think of data we could see for sickle?

Oh, single digits. Single digits. So still very exploratory, but it Yeah, just highly focused on mechanism, showing target engagement, how that might affect markers of hemolysis, that type of thing. Gotcha.

Anything else that we should take away from the presentation at SoHo and just overall kind of the PV opportunity?

No, I think key points are, we believe this is a very large opportunity.

And we believe our molecule is showing signs of potentially having the best profile around the in the space but much more data to be to be developed before we can really make that claim got it well maybe shift gears um to bite a pertinent and apollo you know big face three readout coming out by the end of the year uh maybe you can kind of help tee it up it's been kind of a long journey here in terms of the the experience here but um you know this is going to be consequential for you guys and you know ahead of a first launch so maybe you can kind of just Again, tee it up for us.

Yeah, sure thing. You know, it feels like a long journey. It has been, no doubt, a wild ride. But I would say I'm very proud of the way we've executed as a company on this molecule in this disease space, a rare disease. When we came into it, only one and still only one approved product, which works by tanning and requires a surgical implant. And we went in, ran two phase two programs, open label in Australia, placebo-controlled in the U.S. And we feel like we've tapped into a pool of patients who are really hungry for a new therapy. And, you know, actually, those patients have become quite active of late and have put a lot of stories of their experiences out in the media. And it's just an honor to feel part of doing something that may eventually help these patients. So if you look at our timelines, we've actually been incredibly efficient moving this molecule through phase two and then into phase three. The wild ride, of course, came from an effort where we were, you know, we asked and were, in a sense, invited down an accelerated approval path with the FDA. Ultimately, you know, they felt like the surrogate endpoint didn't adequately predict clinical benefits, so we got a CRL back in the winter, which was particularly surprising because we'd been chosen for the commissioner's national priority voucher. But you know what? It's okay. Through all this, we kept our eyes on developing what we think is going to be high-quality, definitive clinical data. So he had built the Apollo trial as a confirmatory trial. But we had discussed it with the FDA in a way that it was designed to be, you know, support a pivotal, play the role of a pivotal trial in case we needed to retreat back to a traditional approval path. And so that's where we are. And, you know, thanks to just the high enthusiasm from the doctors and the patients, the trial enrolled much faster than expected. And so here we are, you know, just about six months after our CRL on the cusp of delivering data from that trial. So we're very excited about it. And we feel like we learned a tremendous amount from the Phase II data set. It was our first experience with these time and light endpoints that are recommended by the FDA as a way of demonstrating a clinical, what they would view as clinically meaningful effect of the drug and so with that phase two experience we think we are able to design a phase three trial that is you know loaded to to give us a successful readout to convert those signals that we saw in the phase two into just a clean stat sig phase three result but of course there's a risk around that there always is and I think you see the markets all kind of taking their position up or down on on our probability of success but we're tremendously excited about how this is going.

Got it and again maybe an interesting question but like what have you learned through this whole process around kind of like regulatory and working with the FDA you know given the fact that you kind of round-tripped here and we're back to just you know focused on a registrational phase three but you know you recently had a conversation with the FDA to align and ensure that you're aligned on Apollo but you know I don't know any kind of key learnings that you've kind of come along the way over the last like 18 months?

Well, I think we learned what everybody I think already knows which is that accelerated approval is a highly controversial path in the industry, in the regulatory space. There've been a number of drugs that achieved that approval and then confirmatory trial forced everyone to pull the drug back again. And I think it's created a lot of controversy inside the agency. And we were part of that controversy and came out on the adverse end of it. And I'm just grateful that we kept our eyes on the prize of getting a really good definitive Phase III trial done in the background while we were having those conversations with the FDA. And I think there's, you know, general alignment between us and the FDA that this trial will, you know, can be the supportive data to respond to the CRL and support traditional approval in the end.

So, you know, in the CRL, and, you know, you've kind of talked about this, but I'd love to get, you know, kind of the updated view in terms of, you know, we know BIDO lowers PP9, but, you know, kind of that association between, you know, changes in the sunlight endpoints, you know, that correlation. How do you kind of get confident there, and ultimately, what will the FDA be really looking for as the outcome of the phase three trial? Are those co-primary endpoints enough, or are they going to kind of look down to the patient-level correlation or certain thresholds? Like, what additional analysis might they do on the Apollo trial?

Right. Well, the correlation between protoporphyrin-9 and the time and light endpoint, that's a creature of the accelerated approval. where you have a surrogate endpoint, which in our case was supposed to be protoporphyr nine, and they want you to demonstrate that it's reasonably predictive of clinical benefit. And that's where you get into a discussion of, well, how do you demonstrate reasonably predictive, right? And reasonable parties can disagree about what the level of evidence on that would be. And you saw in the CRL, the FDA looking for a particular kind of correlation between those endpoints. And it didn't meet, you know, the standard they were looking for so be it now with the Apollo trial data coming the co-primary endpoints are protoporphyr nine and time and light now just focused on month six of the study and that was designed to avoid some of the placebo effect that we learned around learned about in phase two and these are we just need to hit those two co-primary endpoints the question of correlation doesn't matter anymore we fully expect that they will show a relationship and some association, as they did in Phase II. But that's no longer a part of the regulatory conversation. Really the focus is just, are you demonstrating a statistically significant and clinically meaningful benefit for the patients? And we believe that the time and light should be sufficient to achieve that, given that SNES, the one approved drug, was approved on a very similar endpoint in about a 50% effect size that they were able to detect in their study now we have secondary endpoints and probably the most important of which is reduction in phototoxic events these pain attacks the patients get when exposed to sunlight our data were very robust on that in phase two and we're hopeful that we'll you know be stat sig on that as well I think that would be a really nice kind of evidence of what we think is a profound effect this drug may be having for these patients got it and it would be great to kind of walk through the end point here and kind of the window that you guys are looking to kind of measure you know these um you know efficacy end points and i guess the question really it comes that we get is like again the variance around here and in terms of like behavioral patterns of these patients and seasonality so maybe you can just walk us through and what gets you confident right right yeah no there's no doubt this this way so so the what the way that the endpoint is administered is the patients receive a handheld device, an iPhone or whatever, and it has a diary on it where they can record each day the amount of time they spend exposed to light. And it's, you know, the light that's meaningful to them in their disease state, right? Some patients, light coming through a window will trigger their disease. And they're just supposed to track that every day. And if they don't, you know, they're reminded of it. We have very good diary completion rates from phase two and similarly from phase three. And at the end of the study, we apply an algorithm that looks at the time between 10 a.m. and 6 p.m. each day, totals it up. If the patient's had a pain attack on that day, it censors that time out, so we don't get credit. The drug doesn't get credit if the patient had a pain attack. And you can sum that up across the entire study. you can also sum it across a smaller time interval. And what we learned in phase two is that if you sum it across the entire time interval, you know, with our drug, patients don't know if they're on it. It's truly blinded. The other drugs that have been studied in this space work by tanning. So patients become very quickly unblinded, and that was kind of the historical data we were looking at as we were designing our phase two program. We realize now, oh, that actually greatly affected the placebo response. But what we learned in phase two is that pretty much everybody will initially come in with a lot of exuberance into the trial Push themselves put up more time and light than they normally do And so you'll see every group going up fast faster than they should and then the placebo group tends to come down the active groups tend to hold steady or even Increase over time in fact in our long-term extension study. We just see patients Spending more and more time in light which makes sense, right? So biochemically the drug is giving patients their benefit within a matter of weeks. And then it basically plateaus and stays stable for years. But patients have a lifetime built up of avoiding light, and they need to change their behavior to take advantage of what the drug is giving them. And that's why we see this kind of trend upward in time of light in the active groups over time. So looking at that from phase two, it was pretty apparent that measuring the time and light across the entire study as the endpoint injected a lot of placebo noise into the trial, like non-drug related effects into the trial. Whereas if you looked at the last month, you really started to isolate in on the drug effects. And so, you know, to design a pivotal trial that would efficiently detect a drug effect, we thought it would be best to just look at the last month. And we probed whether it would make more sense to look at the last two or three months, last two weeks, you know, we looked at what interval would kind of minimize the variability, and the sweet spot seemed to be about a one month, a one month interval. So that's why we chose month six, and then from there we used our phase two data to assess the variability of the endpoint, and like you say, it is a highly variable endpoint, there's no doubt about it, but what you got to remember is we're looking for about a 50% effect size, right, and we actually took substantial discount on effect size so in months for the last month of the phase two Aurora trial effect size was 14.9 hours we used 11 hours instead for our power and calculations and that was based largely on essentially averaging months two three and four of the Aurora study where you you know you're just starting to separate away from from the placebo group so we think we were conservative on that and if you look at the variability is 24 hours so very substantial variability and you plug that into the calculator comes out with a predicted you get 80% plus powering with 150 patients and you know I think it's worth reflecting on that for a minute we're trying to detect a 50% effect size in many with most endpoints you could do that with perhaps 20 or 30 patients in a very straightforward way but to deal with all of what you said this is a behavioral endpoint patients show quite a bit of variability in how they behave it's how much time they choose to spend in light there are seasonal effects for sure and and there are regional effects and we stratified by region and by baseline severity to try to make sure we account for some of that but fundamentally all of that variability is accounted for in the phase two data and that was you know 75 patients now we're at 150 and in the end we enrolled 183 because of the enthusiasm for the trial and so we feel very good that that this trial is powered to convert those signals that we saw in phase two into a clean statistically significant signal for phase three super helpful I mean you guys did a you know a sample size re-estimation back in January and you

everything that you just said, I guess, you know, what did that tell you kind of about some of the actual variants that's going on in the trial? This is based on the daily diary, you know, if I recall. So, you know, I guess how does that get you more confident based on trial design that you just outlined?

Right. No, no, exactly right. And that was, you know, part of our anxiety was, well, we think we're going to administer the phase three trial exactly the way we administered phase two. We think the patients are going to behave the same. And if that's true, all of our calculations should work out and but to check that we put in this blinded sample size assessment to look at the first 50 completers which would be about a third of the intended 150 and and and so we did that that that that came out in January and in fact if you apply the same calculation that we applied in the powering it was essentially right on right on target so the very this is just looking at the variability yeah no there's no unblinding we cannot say anything about the effect size, but at least in terms of variability, the phase three patients seem to be behaving exactly the same as the phase two patients, which is very encouraging, right? It says, okay, the math we've applied to design a successful phase three trial appears to be on track. Gotcha.

So I know you said by end of the year, but any more granularity in terms of timing?

Let's just stick with that. I would say it's Q4 is the guidance. And I guess it's publicly known that we had our last patient in in March in fact that's we cut off we had to cut off enrollment in March and then so last patient last visit is going to be in September because it's a six-month study and then I think everybody can you know run their own mental algorithm of how long a company typically takes to turn that into a top-line readout.

Perfect so maybe just So let's touch on the market opportunity. So you guys had kind of been doing a bunch of work identifying patients and starting pre-work on the centers ahead of the CRL. And then now we're kind of getting ready for launch again. So maybe just talk us through some of the things that you guys are doing today and ultimately how should we be thinking about the market opportunity, the size of the market here?

Right, right. Yeah, so I think, you know, if you start with the kind of the outer boundary estimates from Mass General of genetic prevalence in the population of this genotype that's responsible for EPP, it's estimated at about 20,000 in the U.S. That's substantially larger than academic estimates that had previously put the mark at about 3,000 to 4,000 U.S. patients. So you have these widely disparate estimates. we went to claims data, what we saw in the claims data, with pretty careful scrubbing and a lot of kind of secondary checks on reliability, put it at about 14,000 patients who have received care under the code for EPP. Now of those 14,000, 8,000 of them only had one code, right? So it tells you that that is not a patient that's not highly engaged in their care. And typically the profile is that they're seeing a GP or a dermatologist out in the community. So you have about 8,000 of these what we call kind of less engaged patients out there. But then that leaves you a core of about 6,000 who do seem to be engaged in their care and that's now getting closer to the number that the academics predict. So somewhere in that three to six thousand range is what we believe is the kind of proximal approachable market of patients who are engaged in the care and should be straightforward to activate once there's, you know, if there's a promising new therapy. So that's looking at through the lens of claims data, kind of epidemiological studies by caregivers. We also, you know, despite the, you know, the wildness around the CNPV where we had to hire and then let go of some of our commercial team, we did retain about half of our sales force they have, as well as an MSL team. They can't talk about our product, but they're out discussing the disease with with doctors and trying to just you know talk to people about how they're diagnosing it whether they've heard of it whether they have patients on it and that effort is you know continuing to tally up patients who we think are real so and then of course we have our own trial patients and we have an expanded access program as well so when we get to you know we hope we get to launch we'll have a pool of patients who are already on drug through our extension studies and that's probably going to be in the ballpark of 150 patients in the U.S. Then we'll have additional patients from the EAP where demand is very high but we haven't shared yet the number of patients there. Then we'll have, you know, we estimate probably about 600 patients who are seen at the Centers of Excellence. These are our trial sites. Doctors very well known to us who are I think very enthusiastic about this mechanism of reducing the toxic metabolite, and then from there, you know, it'll be a broader reach into that initial 3,000 to 6,000 patients, and then getting to that full 14,000 claims database number, you know, what we think will represent peak sales, that's going to take time. That's going to take, you know, kind of really bringing in patients who, you know, I think have had a very discouraging run with their disease, where they get their diagnosis, they don't have a lot of therapeutic options, they end up just living a life kind of designed around darkness basically how do you think about you know the incumbents and s in in that market and you know ultimately how are you thinking this market overall evolves and you know there's other additional competitors soon to be in the market also so yeah how do you think this kind of market goes from basically one therapy kind of sub-optimal to multiple therapies that will be available yeah so sin s you know it's hard to estimate exactly how many patients are taking it because you can't tell who's taking six doses versus one dose in a year we think compliance is poor but probably measured in a couple hundred patients right so it's a very I think a small minority of patients who are accessing that drug and it's no surprise because they have to travel to one of a handful of centers where you can do the surgical implant and it's just not a great kind of repeat modality for people so and I think in you know Clinivelle's recent report, they noted, in fact, their sales are going down because patients are going on to other trials. And I would assume that's us. And that's also a drug called their semelagin, which is an oral tanning agent that, you know, initially failed the first phase three trial, but then read out positive from phase three and is now also in an approval process. So I assume the market will be kind of taken over by oral agents, which are going to be more straightforward for patients. And I didn't say it, but Bitterpertin is a once-daily very convenient and then you know I think from there it's going to depend on clinical data you know we know from their own stories that there are many patients having a great experience on bitter pertin they've been public about that we know that physicians are excited about the ability to not just put some kind of barrier against the sunlight but actually reduce the toxin buildup inside the body they see the potential that that may benefit liver health and other aspects although to be fair that won't be proven out in our phase three trial and so I think we're gonna have a competitive profile the tanning agents have tended to have difficulty showing a reduction in in pain attacks as I said as I mentioned our data was quite robust on that in phase two and if we're able to kind of hit that that's again phase three I think that'll be a powerful differentiating feature.

So based on kind of the the patients that you noted that are kind of accessible at launch I mean what's your anticipation in terms of the ramp should a typical rare disease launch do we see bolus and then kind of you know steady growth afterwards or just kind of steady Eddie what would be your expectation?

Yeah well I mean I think there will be the straightforward transition of patients from who are already on therapy on to commercial drug. And I think there will be also a fairly rapid update in centers of excellence. And then I think as you get to the broader market, that's probably a slower curve. So you could view it almost as three different superimposed curves of launch going on, you know, the conversion of patients who are already on drug, the access to patients who are already being seen at top centers where a kind of awareness of new therapies is going to be very high, and then a slower, longer term ramp into the broader population where there's a certain amount of kind of finding that the treating physicians, making them aware of new therapeutic options, hopefully activating those patients and providing them with new options.

Well, John, I think we'll leave it there. Thank you so much for the discussion. Great. Thank you.