Good morning, everyone. My name is Yathin Suneja, one of the biotech analysts here at Guggenheim. Welcome to our SMID Cap Biotech Conference. It is my pleasure to introduce our first presenting company of the day, Dianthus. From the company, we have Marino Garcia, who's the Chief Executive Officer. Marino, why don't you maybe spend five minutes, give us an overview of the company, highlight some of the key value-inflecting milestones that are coming up that we should be focusing on, and then we'll go into the Q&A discussion. Sure. First off, thank you, Yathin, for this invitation and to Guggenheim for this opportunity to update everyone on the great progress the team at Dianthus is making with our lead program, 103. The team that I'm very fortunate to work with is building a fantastic, exciting autoimmune company by rapidly advancing our lead program, DNTH103. DNTH103 is an antibody that selectively targets the active form of C1s within the classical pathway of the complement system, and that brings potentially significant benefits and a highly differentiated treatment option in the future for patients with neuromuscular conditions such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy, the three first indications we are going after as we leverage the pipeline and the product potential for DNTH103. By going after active C1s inhibition and the classical pathway, the benefits that that brings is that we can address those three conditions I mentioned, which are classical pathway-driven diseases, with a highly potent antibody that leaves the lectin and alternative pathways intact. The benefits of that and what could eventually lead to is that we can deliver a very low volume, so 300 mg in a 2 ml autoinjector that can be self-administered every two weeks for patients. By going after the classical pathway, we can deliver the kind of efficacy folks are used to in conditions like myasthenia gravis from the C5s, Ultomiris or Soliris, for example, but reducing the risk of infections from encapsulated bacteria because DNTH103 leaves the lectin and alternative pathways intact. Those are the pathways required in order to fight against the risks from encapsulated bacteria, such as meningitis. There's a C1s inhibitor that's already on the market, Enjaymo, sutimlimab. It's indicated for cold agglutinin disease. If you look at its label, you'll notice that it is the only complement inhibitor approved on the market with no boxed warning for any safety issue and no REMS program. That kind of safety differentiation is because it's a classical pathway inhibitor and leaves the lectin and alternative pathway intact. If you can imagine, what we're trying to deliver for patients at the end of the day is a label that is composed of three parts of three best-in-class labels already approved on the market today. If you can imagine, the efficacy and indication is cut and paste from Ultomiris or Soliris. Essentially, highly efficacious, approved for Myasthenia Gravis. That's the target. Then, in terms of safety tolerability, go to the sutimlimab label or Enjaymo label, cut and paste the safety and tolerability section. Even though they have to administer 25 times more drug than we're aiming for, it doesn't matter. Just take the safety and tolerability label, put that into our future target label, and then, from a dosing administration profile, essentially, take the Dupixent dosing administration part of their label, cut and paste that. So if you can imagine an offering for patients in these three conditions we're going after, MG, MMN, CIDP, where you can have a best-in-class efficacy, a best-in-class safety, and a best-in-class dosing administration with a self-administered autoinjector every two weeks, that offers a huge potential for treating a broader population of MG patients and moving it first line into younger, healthier, let's say, more active patients than those who are receiving biologic treatment today. So that's the focus. And what's exciting is 2024 was a year of significant execution. We started those three different indications. We started the Phase 2 for MG. We started the Phase 2 for MMN. And then, I think to the pleasant surprise of some investors, we actually announced that our CIDP program is a single pivotal Phase 3 program, which is now up and running. The first catalyst we have with patients in Phase 2 is actually coming in the second half of this year. It looks like the data may be announced. It's on the cusp of Q3 and Q4. As soon as we have our last patient enrolled, we'll update the Street specifically. When exactly we'll have data from our MG program later this year. And that will very quickly then, in 2026, be followed by the MMN data from our Phase 2 program, as well as an interim responder analysis announcement from our CIDP program, both of those in 2026. Got it. Very good. Marino, thank you so much for that sort of overview. So before we actually go into your myasthenia gravis and other programs that you have, just maybe if we step back. So there are two players, right, in this field. You guys and Sanofi both have an active molecule in development. Can you just talk about the differentiation that you bring in? It seems like you have a more potent, more just I want you to do articulate for us. Sure, sure. Yeah, so Sanofi actually launched the first generation C1s inhibitor, which is Enjaymo, sutimlimab. It was approved over three years ago for cold agglutinin disease. The issue with that first generation C1s inhibitor is that it binds not just to the activated form of C1s, which is what's really implicated in the initiation of the cascade that eventually leads to the MAC. It also binds to the proform of C1s, which is more abundant, significantly more abundant than active C1s. So they have to give a significant amount of drug. So it's literally 6.5 to 7.5 g of antibody by IV every two weeks. They recently sold that product to Recordati for $1 billion, which I thought was a really nice development in the C1s space. They're now focused on developing their active C1s inhibitor, riliprubart. They have two Phase 3 programs ongoing right now in studies in CIDP. What's exciting about riliprubart is that it was a very significant catalyst and actually a bit of a turning point for Dianthus, because starting about a year and a half ago almost, they started putting out interim data from their open label Phase 2 study in CIDP. It's actually the first time an active C1s inhibitor has been shown to work in any neuromuscular condition. It's actually the first time a complement inhibitor has actually been shown to work in CIDP. That efficacy data they put out in three different patient groups was really impressive. They had their Phase 2 data in CIDP, and they broke it out into patients who were on IVIG and stable and doing fine, patients who were on IVIG but refractory to IVIG, and those patients who were naive to IVIG. In those first two groups, the patients who were doing fine on IVIG and switched to riliprubart, as well as the refractory switch to riliprubart, they had about a 50% improvement. I mean, that's a very significant efficacy signal. I would just remind people that if you were refractory to IVIG, you wouldn't be switched to FcRns because FcRns wouldn't work in IVIG refractory patients. So that very strong signal seems to suggest there's something about active C1s inhibition and classical pathway inhibition that could be of huge benefit for a significant number of CIDP patients. So riliprubart, to their credit, are doing two studies. One is in refractory IVIG patients versus placebo. And then the second one is a head-to-head study versus IVIG, a non-inferiority study. And I think that displays confidence that active C1s inhibition should be at least as efficacious as IVIG, which is the current gold standard, and considered more effective than FcRns in CIDP. So then the question becomes, and so that had a very significant impact on us because they're dosing 600 mg in 4 ml subcutaneous shot every week versus our 300 mg 2 ml shot every two weeks. So if you were to dose these two products in autoinjectors, we're talking about two injections, two subcu autoinjectors a month for DNTH103 versus eight for riliprubart. And the question then becomes, well, how are we confident that we can get at least similar efficacy, if not better, with much lower dosing and less frequent injections? The reason is we just have a much more potent antibody, and if you look at our corporate presentation, there's a slide that we put together where we conducted six different in vitro head-to-head potency experiments, and we include all six of them in the slide to let investors pick and choose which ones they prefer, but the one we really like to focus on is the CH50 hemolytic assay, where you see that to reach the IC90, in other words, the 90% inhibition of the classical pathway, which is considered very strong and powerful inhibition of the classical pathway, you can see that we are seven times more potent. In other words, we need to give seven times less drug or achieve seven times lower PK levels than riliprubart to achieve that 90% inhibition of the classical pathway, so that led to a lot of excitement. And we were able to execute on a pipe just over a year ago for $230 million, which, quite honestly, was driven mostly by this exciting development in the CIDP space. So like I said, we're very confident in the CIDP program. We believe we have the best option for those patients. And so we went straight into a Phase 3 program. And that was initiated toward the end of the year. If you like, I can again. Yeah, just. If you're familiar with the ADVANCE study from Argenx, I was very impressed by what Argenx achieved there because back in June, they achieved, with their highly enriched study, an indication in the U.S. for all adults with CIDP, and so we decided we needed to take that same approach because we can't think of a design for a program in CIDP that could have a higher probability of success, so we replicated the study with a couple of important differences. We have a part A open label and a part B randomized placebo-controlled portion. But in terms of the lead-in, we are not making patients have to fail. We're not taking away the IVIG and making them fail on the therapy to confirm their diagnosis. We are switching immediately to DNTH103. Physicians are much more comfortable diagnosing CIDP now. And we'll have an independent review board of KOLs that would look at every single patient and confirm whether they have CIDP or not. We eliminated that because it'll make the recruitment to the trial really, really difficult and potentially lead to delays. And it's just not necessary. The CIDP market or space has really evolved very quickly in the last few years. The other important difference is we are actually allowing refractory patients into our trial. As I mentioned earlier, riliprubart's data was very impressive in that patient group. Obviously, FcRns wouldn't allow refractory IVIG patients into the trial. So that's something we will be able to provide data in the future on, and those patients with a very high unmet need in the CIDP space. So those are two of the important differences. Part A is essentially putting patients open label on 300 mg every two weeks. If at any point up to 13 weeks, starting week five, patients respond, in other words, have an improvement by at least one point on the INCAT scale, they immediately then get randomized into part B, which is a blinded randomized placebo-controlled piece. There, they can either go into placebo, 300 or 600 mg. Got it, got it. So why not include the 600 mg dose in part A? We don't believe we're going to see a difference in efficacy, to be honest, between 300 and 600 mg. OK. The 600 gm is there just to test or answer the question, is there potentially any additional efficacy you can get by going even to higher levels of inhibition of the classical pathway? 600 mg essentially just gets above IC95. Our 300 mg every two weeks is already significantly above 300 mg, sorry, above the IC90 or 90% inhibition of the classical pathway. So we really don't believe you need to go to 600 mg every two weeks. Of course, our MG data later this year will be very informative, and we'll see what kind of difference there is, if any, between the two doses, at least in MG patients. But let me just say this. We know we have a much more potent antibody than riliprubart. Riliprubart had very impressive efficacy. And yet, in our experiments, in our head-to-head experiments, we're anywhere from four to 12 times more potent, depending which assay you focus on. So we are already delivering, at a minimum, the equivalent dose to riliprubart in that open label, if not even more. Yeah. I fully expect that 300 mg will be the right dose. Yeah, so from part A to part B, only the responder go in. But the one thing which is unique in your study is that you are not doing the test in the beginning, right, where you're not taking it off. Right. So if patients come stable, if those patients are stable when they come in, do you expect a similar percentage to respond as we have seen it with others? Yes. OK. Absolutely. We've consulted physicians, KOLs, as we were designing this program. And I think Immunovant even had some issues with delays because of that. And they have said in the future they're not going to do that anymore. When we talk to physicians and KOLs, they are much more comfortable with CIDP. There's been a huge evolution in the CIDP market, just as we saw with MG market maybe 10 years ago. And like I said, we're not just going to let the investigators decide if these patients have CIDP. We're going to have an independent review board review every single patient that gets recruited into our trials to confirm that they have CIDP. Got it. So we're very confident that there's no need to put patients through that. And frankly, I think it would be almost impossible to execute on a trial if you try to do that anymore. One more question. So Sanofi and Argenx, Sanofi, obviously, with their study, what their C1s is head-to-head versus IVIG. Now Argenx, with their C2, also doing head-to-head versus IVIG. What do you think about that? Could that have an implication? Because if they run those studies and they have data on label versus IVIG, which you probably would not, how does that play? Or do you need to do something versus IVIG? So let's focus first on riliprubart, right? Yes. So in the end, riliprubart will have their data in the first half, I believe, of 2026, the study versus placebo for refractory patients, as well as this non-inferiority head-to-head versus IVIG. There's two potential scenarios. Well, there's actually three. But let's assume there's only two potential scenarios in the head-to-head versus IVIG. Either they show that they're just not inferior, and I think most of the market would be, OK, that seems to make sense based on the Phase 2 data. If they show superiority versus IVIG, that's going to have a significant plus for the classical pathway class or the C1s inhibitors, active C1s inhibitors, which there's only one other one, and that's us. We will have data in these three subgroups: patients who are refractory in switch, patients who are stable in switch, patients who are naive and started on. If they show that they're better than IVIG, we're both going to end up with the same indication, all adults with CIDP. And if the market and my future chief commercial officer tells me that it would be good to also have some head-to-head to show that we also are superior, let's say they show superiority, then we'll just do that study. And we'll execute that fairly quickly. But my guess is that if they just show they're basically non-inferior but have all these other advantages versus IVIG, convenience or subcu and just much better tolerated for patients, then I don't think there's a need for us to do a head-to-head study. But we'll see. Very good. But you also mentioned empasiprubart, the C2 inhibitor from Argenx. That's a Phase 3 program. Yeah. I'm assuming that was a good in-depth discussion with KOLs as well as the FDA. When we are done with our Phase 2 trial and we talk to the FDA, if that's the design that makes sense for us to go forward with, we'll also replicate a head-to-head study versus an MMN versus IVIG in our Phase 3 program. And that's a very exciting development. And I think that shows some confidence potentially from Argenx that in CIDP, where they're taking this empasiprubart and doing the head-to-head study versus, sorry, an MMN, as well as CIDP, by the way, they're going after, I think they're just very confident that classical pathway inhibition has significant benefits and can be shown to be at least equal, if not potentially superior to IVIG in these conditions. That has very positive read-through to us because it's all driven through the fact that they inhibit the classical pathway with their C2 inhibitor. What is the timeline for your CIDP study? The study is now up and running, or we're initiating sites. The only guidance we've given is that we will have an interim readout of the first 40 patients from our open label portion of the trial in the second half of 2026. Got it. That's much like Argenx did. I think they did it with 30 patients. We're doing it with 40 patients. OK. I think that's on CIDP. Move to myasthenia gravis. Tell me how the enrollment is ongoing, how many patients per cohort you are enrolling, what is the endpoint, and what your expectations are? The study design for MG is three arms, placebo-randomized control, of course. It's placebo, 300 mg every two weeks and 600 mg every two weeks. We're aiming for 20 patients in each arm. This would be the largest Phase 2 MG program that we know of. The primary endpoint is safety. It's a Phase 2 program. Of course, we're also looking at all the efficacy measures you would expect, secondary endpoints. If we see the impressive efficacy similar to what Ultomiris and Soliris have in their labels, say a high 1.6 to 1.9 or higher, we will have a positive p-value on the study on the MG ADL, for example, which is, I think, what most people will be focused on first. The study is enrolling well. We're on track. As I said, right now, it looks like we would have data somewhere in the cusp between Q3 and Q4 as soon as we have 100% certainty. In other words, when we have our last patient enrolled, then I'll provide an update on guidance on when exactly to expect that top-line results from that Phase 2. Got it, got it. On the efficacy bar, you know, 1.6 to 1.9, I mean, some of the FcRn are in the twos. Is that not possible with the pathway? I'm just curious, like, how are you coming up with it? It's absolutely possible. It's just when I look at the market and I see Ultomiris and Soliris selling AstraZeneca, just announced $6.5 billion in a franchise, driven mostly by Ultomiris, which grew 33%. And they're saying the vast majority of that growth is coming from MG in the U.S. with patients who are naive to biologics. In other words, still being used first line. Wow. I know there's some feeling out there that maybe the C5s are being or Ultomiris being reserved for after FcRNs. That's not true. They're still being used quite a bit of first line, even though, again, they're more expensive and have that boxed warning. So when I see that, there is nothing that beats Ultomiris in terms of its efficacy, in terms of onset, as well as continuous symptom control. This is a chronic condition where the MG-ADL is a self-administered patient scale where any time you see their scores coming up, it's them telling you they're feeling symptoms. They're feeling like they're getting sick again. And if you look at the FcRn or efgartigimod, you see this cycle that patients go through. They feel pretty good at maybe week three, week four. You can see that they get to that around two-point difference. But then week five, six, seven, eight, they're getting sick again. So to me, the efficacy that I would want as a patient with a chronic condition like MG that I would, and the therapy that I would want my family members to be on if they had MG, is one that gets their symptoms under control and keeps them under control because it's a chronic disease. So when I look at the efficacy bar out there, I look at Ultomiris as an extremely successful complement inhibitor and the gold standard for efficacy. Of course, if we have a higher difference on the MG-ADL, it's great. But if you're in the high ones, you've met the bar for efficacy in terms of expectations from the gold standard, which is Ultomiris. Got it. Very good. So in terms of the enrollment, do we have a sense when you might be able to narrow that down to either Q3 versus Q4? Or how it is trending since you start? What is the trajectory of the enrollment? My team is probably listening right now and saying, come on, Marino. Look, by the spring, we'll know for sure. The other thing that we keep getting from investors is that there is an oral compound that is being developed by another competitor. Any view on that oral compound, the Annexon C1s? Yeah. So they say they have an active C1s inhibitor that's oral, I believe, BID. Yeah. Fairly high doses, and that they're doing a proof of concept study in CAD called the cold agglutinin disease. It's interesting. Years ago, when we were a private company, we considered doing a CAD proof of concept study, but I could not get an investor to tell me that if we showed any efficacy in CAD, that that could be translated to anything in any neuromuscular condition. They would say no, so we decided not to do it. We didn't think it would be useful, but we just need to see data because it's been very difficult to really understand. How potent is it really in inhibiting the classical pathway? Does it get to that 90% bar that we all have for efficacy in shutting down the classical pathway? What's their impact on hemoglobin and bilirubin? Hemoglobin, if you look at the Enjaymo label for cold agglutinin disease, they have a significant impact right away at week one. It doesn't maximize. It takes a few weeks. But still, at week one, it looks like it even separates from placebo. So they have a short study in CAD. I would want to see those two endpoints. And very importantly, the tolerability profile. So tell me how potent you are as an active C1s inhibitor. Tell me your impact on CAD on the two endpoints. And a safety and tolerability table because an oral high-dose BID drug could have significant GI side effects. Very good, Marino. That's all I had for you. Thank you so much for your time. Thank you, Yathin. I really appreciate it. Thank you.