Good afternoon, everyone, and welcome to another installment of Oppenheimer's 35th Annual Healthcare Conference. We have with us CEO Marino Garcia of Dianthus Therapeutics. Marino, if you could start out by introducing yourself and give us a brief overview of Dianthus? Sure, thank you, Trevor. And before I start, a quick thank you to Oppenheimer and you for the invitation to present today. I really appreciate this opportunity to update everyone on the great progress the team at Dianthus is making. And of course, I'll be likely making some forward-looking statements, so I would just refer everyone to our website and our investor page to see any of our recent SEC filings for any more information. So Dianthus Therapeutics, we came out of stealth just under three years ago with a Series A $100 million and built a team. At that point, we had, and we still have, our lead program, which is an active C1s inhibitor. It's a complement inhibitor that binds only to the active form of C1s within the classical pathway only of the complement system. Since then, it was preclinical, and since then, we've been able to finish our phase I study, which confirmed that we have a very potent active C1s inhibitor with a nice long half-life of about 60 days. The whole idea behind DNTH103, our active C1s inhibitor, is to essentially offer for patients who are suffering from classical pathway-driven diseases like myasthenia gravis, CIDP, and MMN a very effective, potent complement inhibitor that potentially has a differentiated safety profile, meaning a lower risk of infections, can avoid a box warning in the REMS program that you see with other complement inhibitors, and also in a very convenient dosing and administration profile of being able to self-administer a subcutaneous autoinjector every two weeks, a Dupixent-like dosing and administration profile. As I mentioned, we had that phase I data with confirmed. We have a very potent inhibitor of the classical pathway and only classical pathway, leaving the lectin alternative pathway intact. And we have now begun. Last year was a very busy execution year. We started three programs. We started about a year ago on the MG program. It's a phase II trial. We started the MMN program mid-year, a phase II trial in multifocal motor neuropathy. And at the end of the year, we announced that we're going forward with a single pivotal phase III trial in chronic inflammatory demyelinating polyneuropathy, CIDP. And so now we have those three trials up and running. And this year and next year are essentially very important years. I mean, they've all been important, but this is now where we actually see what the antibody can do with patients. So in the second half of this year, somewhere on the cusp between Q3 and Q4, so September, October, we'll have our myasthenia gravis data from our phase II trial. It's the largest phase II trial done to date. And then next year, we will have our CIDP data, an interim responder analysis, as well as the phase II data from our phase II MMN trial. So starting in the second half of this year and over the next 12 months, we'll have our three major catalysts. And the good news for the company is we do have enough cash to take us to the second half of 2027. So a good runway beyond these three very important catalysts in 2025 and 2026. Great. Yeah, so let's start off with myasthenia gravis. It's kind of a crowded landscape. Tell us about where DNTH103 is differentiated within MG. Sure. You mentioned that it's a crowded space, and I get that question a lot. And I do want to put a little bit of perspective on this. The myasthenia gravis, some of our direct competitors say, is already about over 100,000 patients potentially just in the U.S. alone. It's a fairly large and multi-billion-dollar opportunity for an autoimmune market in the U.S. And essentially, there's really only two first-line biologic classes today. It's FcRNs, really dominated by efgartigimod from Argenx, and complement, dominated by Ultomiris, as well as Soliris, but mostly Ultomiris, the C5 inhibitor from Legacy Alexion, now at AstraZeneca. And that's it. It's really two biologic classes. And that's really the way it's going to remain for the next decade. Every other class that's been trying to look at myasthenia gravis, IL-6, the CD19s, CAR-Ts, I mean, they're just not delivering the kind of data or safety profile or ease and convenience that would make it a first-line therapy. If anything, maybe it'll be more like third line. So as far as we can see, there's only really two biologic classes competing, which is not terribly competitive. And then within each, there are multiple products. But if you look at complement specifically, it's dominated by C5s today, terminal inhibitors. And everything you look at in the pipeline for MG are C5 inhibitors, just one form and others. There's only one classical pathway inhibitor, and that's us. There's only one C1s inhibitor, and that's us. And if you believe MG, like we do, is a classical pathway-driven disease that you don't need to block lectin alternative pathway, we should have at least similar efficacy to C5s, but with a much lower risk of infections and therefore can avoid the box warning around the risk of things like meningitis. And there's nothing in development that has that Dupixent-like ease of use, an autoinjector that people can self-administer every two weeks with our 300 milligram, 2 milliliter dose of DNTH103. So if you believe that we will be head and shoulders the best complement inhibitor option for MG, then we'll just compete with whatever the best FcRn is at the point we get to the market. So is that Efgartigimod? Is that something in another company's pipeline? Whatever you believe is going to be the best FcRn, and that's it. It's two biologics competing for first-line use, and then we'll be each other's first switch. And you know in autoimmune markets, there's a lot of switching going on. When you look at an autoimmune market as lucrative, as big as myasthenia gravis, and you think there's only two biologic classes, and you see that DNTH103 is highly differentiated and obviously going to be our best in class in one of those classes, I don't know how we can think that it won't have room as a first-line therapy and as a first switch therapy. And by the way, C5s are still today being used quite a bit first-line, even with the box warning and the fact they're at least 50% more expensive than Effgar Tigamod. And they're still getting first-line use. If you look at AstraZeneca's latest earnings, Ultomiris, that franchise is still growing, and it's coming from MG and biologic naive patients in the U.S. So obviously, our current thinking is we would launch and price more appropriately for the MG market to compete with FcRNs. So we'll look at what the landscape looks like when we launch and make sure that we have maximum access for patients. So that's essentially how we look at the market, and that's how I see 103 as really just being the best complement inhibitor competing with whatever you believe the best FcRN will be for first-line use or first switch in the MG market. Great. And what do you all see as the bar for the phase III results? Or what should we be expecting out of the top-line results later this year? See, look, when I look at the target product profile for 103, I see if you can match the efficacy of the gold standard continuous symptom control C5s that have been used for over a decade and patients where they respond are very satisfied with the efficacy they see with their C5 inhibitors. If you can match the efficacy, but then bring to bear the safety advantages and the dosing and administration advantages, I think that's a winning profile. And if you look at the label for Ultomiris, Soliris, it's anywhere in the high ones, 16-19. So that's the minimum. That's the bar. Anything above that is a win. Anything matching that is a win because of the safety and dosing administration advantage. Trevor, the way I like to describe for people to really try to simplify, what are we trying to do? We're trying to take the best parts from three best-in-class labels and combine them into one offering for patients with MG. Look at the Ultomiris or Soliris efficacy, C5 continuous symptom control. There's no cycling. There's no patients getting sick within 12 weeks. Just get them down, get the MG ADL scores down, and keep them down continuously. Take that efficacy, cut and paste into our label. Go look at Enjaymo, Sutimlimab. It's the only classical pathway inhibitor approved on the market. It was a Sanofi that's now owned by Recordati. They just sold it for about $1 billion. It is a C1s inhibitor. It binds to both proform and active form. Because of that, they have to give a lot more drug, and it's like six and a half to seven and a half grams of antibody every two weeks. It's a huge amount of drug by IV every two weeks. But take the safety and tolerability profile, even though it's 25 times higher dose than what we're aiming for, I don't care. Just take that, cut and paste. Why? Because it's like the cleanest, safest label for any complement inhibitor. There's no box warning for any safety issue. And then go and take the dosing administration profile with Dupixent. It's exactly what we're aiming for, even the autoinjector. And it's been very well accepted by millions of patients and super easy to use. Cut and paste onto our label. And then you think about a label like that and an offering like that in the myasthenia gravis, efficacy that's been the gold standard for many years from the C5s, the safety of the C1s inhibitor and breakthrough in terms of being able to avoid a box warning around the risk of meningitis and infections from encapsulated bacteria. And the dosing administration of a Dupixent with the autoinjector has been very successful. That kind of offering, intuitively, if you have MG or someone you love has MG, that's really attractive. That is really maximizing patient convenience while delivering the efficacy and continuous symptom control that you want in a chronic condition like myasthenia gravis. Yeah, it seems like really exciting stuff. Do you guys have any estimate of the current market split for complement versus FcRn? And do you have any, I guess, feedback from real-world doc perspective of utilizing those two medications? Yeah, I mean, there are regional differences within the U.S. There's just personal differences. What we've heard is they're still both being used first-line unless there's some significant access issue at a local. Like I said, there could be some regional differences. The C5s are significantly more expensive and do have the box warning, and so require a little more effort sometimes to prescribe. But they're still being used first-line. You hear different things from different KOLs. What I do hear consistently is complement inhibition works. MG is a classical pathway-driven disease. This should work. And as one recent KOL who was interviewed at a different bank, I won't mention the name, but I thought he put it really well. If you do a study with something like 103 and it doesn't work in MG, it's not the 103. It's the execution. So we're making sure we put a lot of emphasis and effort on making sure that we have the best executed phase II trial we can. The good news is we have two shots on goal. We're not just testing our target dose. We're testing a higher dose as well just to see if even greater levels of inhibition than our target dose can achieve have any additional benefit. But essentially, it's taking two shots on goal. And it also provides patients two-thirds of a chance to get on active drug versus placebo. So it helps with accrual too. But anyway, so I'm feeling really good. We'll see later this year, right? But KOLs just have different approaches. If they see someone and they think, "Oh, this person is at a higher risk of maybe from infections, their immune system is more compromised," they might go with an FcRn over C5s. But if they want somebody who's very active and don't want to be coming in every week for an IV or a subcu push and don't want to be cycling with their symptoms, then they'll go with a C5 inhibitor like Ultomiris. Yeah, yeah, great. All right, yeah, let's move on to CIDP. I mean, this looks like another indication where there's clear mechanistic rationale for use. Can you tell us a little bit about the other C1s inhibitor that's out there, Rillipabart, and the data that we've heard? Sure. Riliprubart and Sanofi, frankly, really did us a big favor a year and almost a half ago when they released their first interim data for their phase II for riliprubart, their active C1s inhibitor in CIDP. It's the first time an active C1s inhibitor has been shown to work in any neuromuscular conditions. The first time a complement inhibitor has been able to show to work in CIDP. And what's really impressive about their data is that if you look at it, there are three patient groups they looked at in their phase II. One is patients on IVIG, the standard of care, who were doing fine and switched to active C1s inhibition. When switched, 50% had further improvement, additional improvement, which is a really interesting efficacy signal over IVIG. The second group are patients who are on IVIG and refractory. This is, to be clear, a patient group that FcRns would not allow into their trials because if IVIG doesn't work, it's highly unlikely FcRns will not work. There's a similar mechanism, and if anything, I think the perception, at least what most people believe, is that IVIG is more effective than FcRn. It's just FcRn is a more patient-friendly version of IVIG, so of course, you wouldn't allow patients who are refractory to IVIG into a FcRn trial. Riliprubart did allow them, and patients who are refractory to IVIG when switched to active C1s inhibition or classical pathway inhibition, 50% were improved. That, again, is like, okay, between the improvement for refractory patients and the 50% improvement for the stable patients, there seems to be, we'll see, there's two blinded studies now going on, two phase III trials, but there seems to be a suggestion that at worst, active C1s inhibition is equal to the IVIG, but maybe it's better, and again, we have to see, the Sanofi is doing two phase III trials. One is for refractory patients versus placebo, very standard blinded placebo-controlled trial. The other study is interesting, a non-inferiority head-to-head versus IVIG. They'll have those results, I believe, in the first half of next year. They said they would file for the indication by the end of next year, so I'm assuming that means results come somewhere at least six months before they file at the end of the year. That head-to-head non-inferiority trial versus IVIG, if it hits, it means it's non-inferior. That's significant because IVIG, in the minds of most KOLs and physicians, is the gold standard for efficacy in CIDP and is considered more efficacious than FcRns. So if you're equal to that, potentially superior to FcRn, if somehow they show superiority, that's a game changer. That really like, okay, now we understand that CIDP is really more of a classical pathway-driven disease than ever believed before. So they have those two studies read out this year. Next year, they'll be very important for us as external catalysts. So the question is, with that kind of efficacy data in phase II and the confidence to go rapidly into two phase III trials, how do we compare? And the difference between our active C1s inhibitor and theirs is that we just have a much more potent antibody. We have a slide where we show like six different assays, in vitro assays that we conducted in a head-to-head, same lab, same reagent, same people confirmed by outside labs who also did repetitive experiments just to make sure all the data is consistent. It just shows we're just clearly somewhere between four to up to eight, 12 times more potent. What does that mean? It means if you look at the dosing and administration, they're dosing 600 milligrams, four milliliters every week. The reason they're doing that is they need to get fairly high levels, PK levels in patients to really shut down the classical pathway, to get above, to get powerful inhibition of the classical pathway. 600 milligrams, four milliliters every week, if you were to put that into autoinjectors, they can take two milliliters. That would be like giving yourself two autoinjectors every week or eight at the end of the month. Our target dose is 300 milligrams, two milliliters every two weeks, so one autoinjector, so it would be eight autoinjectors versus two, and that is purely a result. They have a longer half-life than we do, by the way, by about 15 days. It's not a half-life play. This is a potency play. We just have a much more potent active C1s inhibitor than they do, and on the assay that we believe is the most relevant, the CH50 hemolytic assay, which you can see on that head-to-head slide we have on our corporate deck, it says it estimates over about seven times more potent, but they're dosing four times more drug, so we get above IC90 on that CH50 hemolytic assay. We know we get over 90% inhibition on the classical pathway. I'm not sure if they do. They say they do, but they do use different assays, and it's unclear. So I fully expect we have at least equal efficacy. I believe we're more potent. So we'll have to see if that translates into better efficacy in CIDP in the future. Great. Yeah. Tell us about your phase III design and the decisions you made there. What was feedback from the FDA on the registration? Yeah. No, look, a year ago, I was eagerly awaiting Argenx's results of their filing because when I looked at their trial, their highly enriched trial where they had patients who had deteriorated after being discontinued from IVIG and then put into an open label trial with their drug, and only those patients that responded were then randomized into part B of the ADHERE trial. I was like, how's the FDA going to react to that design? I just don't know what kind of indication do you get, right? Could it be patients who respond to your drug, you can put them on? I didn't understand. They came out with a fantastic label. Kudos to the Argenx team. I mean, they've obviously been very successful. They came out with an indication for all adults with CIDP. The minute we saw that, we said, "We have to do this trial." We couldn't come up with a trial design and an approach to the regulatory filing and eventual approval that had a higher probability of success than what Argenx did. So we said, "Let's do it, but with some important modifications." We're not doing this making patients deteriorate in screening. Nobody wants to do that. We would never be able to recruit into that. Years ago, you had to do that when people were not sure how to diagnose CIDP. The market is much more comfortable diagnosing CIDP now. Even Immunovant, I think, announced that they're not going to do that anymore because they've had some recruitment issues. So we're going to allow investigators to diagnose, and then just in case, we're going to have an independent review board review every chart with every patient to confirm diagnosis. So it's a two-factor authentication process, if you like. Another important difference, as I mentioned earlier, we're going to allow patients who are refractory to IVIG into our trial. The Rillipabart data is very compelling that there's potentially something about active C1s inhibition, classical pathway inhibition that could be superior even than IVIG. There's no reason to not allow refractory patients into our trial. Of course, the FcRNs wouldn't allow that. And we're testing two doses in part B. So we're testing all patients on 300 milligrams twice a day. Sorry. Wow. 300 milligrams once every two weeks. That's open label, part A. And only patients that respond there will go into part B. And in part B, we do have two arms, active arms, 300 and 600, a higher dose. We also have that in the MG trial. We also have that in the MMN trial. And of course, placebo. And that is the trial that we agreed to with the FDA as a single pivotal trial that we could take to potentially an indication if successful. Yeah. What might we see in the interim analysis that you haven't designed in that trial? If you look back at what Argenx did, I think they announced their interim responder analysis or futility analysis was done with 30 patients. We're doing it with 40, a little more robust number. And all they said is, "It's a go. It's working. We're continuing." The FDA doesn't really like you revealing too much information at that point. So we'll explore, but I think at a minimum, we'll do the same as Argenx. Okay. Great. And then I guess, can you comment on any expectations for enrollment given the fact that Argenx also going to be enrolling a trial here and they're going to be doing it head-to-head versus IVIG? Yeah. You know they're doing that in MMN. And the good news about them taking that into CIDP is it's kind of interesting. It's a validation by our biggest competitor in the MG market, Argenx, that classical pathway inhibition is going to have a role in CIDP and a very important one potentially. The unfortunate thing, if I can say so, for Argenx is that they're taking empasiprubart, which is a C2 inhibitor that you have to give by IV every week or every two weeks. So it's high volume. IV is not terribly convenient. And by being a C2 inhibitor, I don't know how potent a classical pathway inhibitor they are. I don't know how much of the classical pathway they shut down. They have never revealed that. And they said for competitive reasons, they didn't want to reveal that. Okay. Let's assume it's a potent classical pathway inhibitor. The problem is that it also blocks the lectin pathway. The lectin pathway does not have a role in MMN, and I don't believe it has a role in CIDP. Riliprubart shows very excellent efficacy without having to touch the lectin pathway. By blocking the lectin pathway, all you're doing is elevating the risk of infections. The lectin pathway is the pathway in the complement system that's triggered by the presence of encapsulated bacteria. If you are blocking the lectin pathway, you are inhibiting the complement system's ability to go and fight and lyse that offending bacteria. If you look at every complement inhibitor that touches alternative or lectin or both, anywhere past the classical pathway, they all have box warnings. It's very unlikely that they're going to get away with it. They say it'll be a review issue. I mean, the lectin pathway is clearly the most important pathway in fighting against risk of infection, and it provides no real benefit. So between the dosing and administration plus the safety burden, let's assume they're a potent classical pathway inhibitor. They should have efficacy in CIDP, but we still think we have a more compelling offering for those patients. Yeah. Definitely agree. All right. Let's touch on MMN, which you mentioned a little bit. It's another indication that looks derisked following in passing regards data. Can you give us a sense of the market opportunity that's out there and what other players are out there developing candidates in this indication? I'm so glad you're asking about MMN because sometimes, I mean, there's just so much noise and excitement around CIDP and MG. MMN sometimes gets a little neglected, and it is a smaller of the three indications, there's no doubt, but FcRns don't work. It's an IgM-driven disease. It's a pure complement market, and right now, there's only one competitor. It's empecitabar, as I mentioned. It's an IV, weekly, biweekly, or yeah, biweekly, and that also blocks lectin, and they themselves, in their own publication, say it's all about classical pathway with MMN. The lectin pathway is not playing any efficacy role. All it does is add a safety burden, so that's it. So yeah, it's a smaller market, but it's one where we could really own. We could have the vast majority of that market. There's nothing else really yet being developed in that play in the MMN space. So it's always an empasiprubart. And I think if you look at the two products next to each other, it's pretty clear which one I think most people would choose to try first. So I really like MMN. And that was actually our second indication we started, even before CIDP. But thanks to Sanofi, CIDP has gotten a lot of the attention right now and a lot of the excitement. But I think all three of these indications, there's a real strong value proposition that 103 brings to the patients first and most, but obviously to physicians and healthcare as well. Yeah, absolutely. Yeah. Do you have any, I guess, expectations on what the total addressable market could be for MMN? I'm sorry, can you repeat that? Do you have any estimations for the total addressable market could be for MMN in terms of? That's one that there's less information than MG and CIDP. We estimate somewhere between 5,000 and 10,000, but we're continuing to do some work. I think our competitors may have said they're higher numbers, but it's definitely less than CIDP and MG. There's no doubt, but it's still a significant number in the U.S. Okay. Great. And when do you expect to have updates on MMN development? On MMN specifically? We are aiming for the top-line data release for the phase II program in the second half of next year, potentially by the end of this year, certainly by next JPMorgan at the latest. That would be my hope. But all I can say is recruitment is going as we had expected. And so we're still aiming for the data release by the end of next year. CIDP, the same. And MG, like I said, we are looking to have that data released somewhere between Q3, Q4. We're right on the cusp of both. Once we get to that last patient in the trial, then I'll be able to update and give a more specific timing. But yeah, all three of these are really exciting. And the nice thing about them is there's these clear clinical synergies as well as commercial synergies. A lot of the investigators are the same. The sites are the same. And the same with a sales force footprint and a marketing effort. It's all around the same customers. So I try not to look at it too much as what's the size of each indication is that together, it's anywhere from 100,000-200,000 patients, depending on which estimates you look at just in the U.S. alone. And they're all neuromuscular conditions where one really good concentrated effort can maximize value with 103. We're really excited. This is going to be a really, really exciting time for Dianthus over the next year. Yeah. Yeah, definitely. It seems like a really exciting time to be taking a look at the stock. So yeah. Well, with that, we're at time. So thank you all for joining us, and we will see you in the next meeting. Thank you very much, Trevor. Really appreciate it.