Good afternoon, everybody, and welcome at our Guggenheim Healthcare Innovation Conference. I'm Delma Caiati, one of the analysts here at Guggenheim, and it's my pleasure to introduce our next fireside chat with the Dianthus Therapeutics. From the company, here we have the CEO, Marino Garcia, who will—and it's a pleasure to have you here. Welcome. Thank you. Before going into the Q&A part of our conversation, Marino, why don't you set us the stage? I know you have prepared some slides, and I'll lend to you for the introduction of your company. Sure, thank you. Thank you to Guggenheim for the opportunity to present and update folks today on some of the exciting things going on at Dianthus Therapeutics. I'll just go through a couple of slides. Sure, that will be perfect. Like you said. Just first, obviously, I'll be making some forward-looking statements, so I'd please refer you to our website and to our SEC filings for all the risks and other information on the company. Dianthus, it's a really exciting peer. We just had an amazing couple of months. We are developing two autoimmune therapeutics with best-in-class potential, with pipeline and product potential, both of which are aiming to be administered, self-administered by patients in a convenient subcutaneous autoinjector. The first is claseprubart. It's a very potent active C1s inhibitor, which I'll talk a little bit about in the next couple of slides. We just had some very exciting phase II data in Myasthenia Gravis, the first of three neuromuscular indications we're studying the program in. And then DNTH212, which is an exciting bifunctional fusion protein that I'll talk a little bit about later, but that was announced we licensed from Leads Biolabs in October. It is a very exciting bifunctional that targets two validated mechanisms of action to potentially deliver improved efficacy in various autoimmune diseases where both the innate and the adaptive immune systems are implicated. Let me jump into a quick overview on claseprubart. We just—I mentioned we had phase II data in September. It is our first phase II data in any of the indications we are going after. As you can see from this summary slide, we looked at various efficacy measures in Myasthenia Gravis, testing 300 mg, 2 mL every two weeks versus 600 mg, 4 mL every two weeks. What we saw is just very consistent, clear, statistically significant efficacy across all five different efficacy measures, including, of course, the MG-ADL and the QMG, two measures that most people focus on at first. As I mentioned, statistically significant across the board with 300 mg. We did not see any real difference really with 600 mg, a higher dose. It was what we expected, no dose response. Three hundred milligrams, 2 mL is what we will be moving forward with into our phase III with Myasthenia Gravis. We also had AANEM in October in San Francisco presented additional data from our phase II trial. There are two bits of data that are really interesting that we presented. First is we looked at all the placebo patients from our randomized control portion of the trial, and we looked at them going into our open label trial where they started getting 600 mg every two weeks subcutaneously. The reason we did this is what's interesting, it's almost like a mini experiment within the larger experiment. We wanted to see without a loading dose, as patients started taking 600 mg every two weeks and their PK levels or levels of claseprubart started rising, what kind of impact we would see on the MG-ADL and the QMG. The theory was that we don't necessarily have to get above IC90. We don't necessarily have to dose as much as 300 mg every two weeks to see efficacy in conditions like Myasthenia Gravis. The only way we're going to be able to see any data was from patients who are on placebo, when they entered the open label, started getting subcutaneous 600 mg every two weeks with no loading dose. As we saw the PK levels rise, what did we see in terms of impact on the MG-ADL and QMG? As you can see here on the bottom line, that's the MG-ADL. They came in at 8.5, moderate to severe. They had a 2.8 response, which is a pretty robust response for a placebo arm in MG. They got to 5.7 on the MG-ADL. At that point, they started getting drug. What we saw is that just after two doses, where the PK levels are around between 50 micrograms per mL and 65 micrograms per mL, that by week four, after only two doses, they had another 2.5 point improvement on the MG-ADL. What's amazing about that, what's really impressive about that is these are patients that already had a significant response during the 13 weeks on placebo. They didn't know they were on placebo, obviously. They thought they were on drug. They had an additional 2.5 improvement after four weeks, after only two doses. That's at levels that are half of what we would achieve with 300 mg, 2 mL every two weeks at steady state. That tells us that potentially dosing every four weeks, where they would achieve similar PK levels, that potentially this could work in Myasthenia Gravis. The QMG, we saw very similar robust response after four weeks and only two doses for the placebo patients as well. This is data that we are using to give us confidence, along with also some external data which we can get into from our competitors that tells us that Q4 weeks is likely to work just as well as every two-week dosing in the phase III program. The other bit of data we saw, we had, as I mentioned, a 2.8 response on the placebo arm on the MG-ADL, which is a pretty robust response compared to historical MG trials. What we did is we said, what if we had had a QMG screen criteria? We had an MG-ADL of six as a screen criteria, but we did not have a QMG screen criteria. What if we had added a QMG screen criteria of 10? We picked 10 because by picking 10, we would only lose three to four or five patients per arm. What we saw is, as you can see on the right, a very robust response had we screened for the QMG like we did with MG-ADL at a level of 10 or greater. We saw a difference of three points from placebo. This would be a best in disease, best in class level of efficacy on the MG-ADL. There is a precedent for doing this. Zilucoplan, the last C5 inhibitor approved, complement inhibitor approved in MG, which has a 2.1 placebo-adjusted score on the MG-ADL on the label, which is the highest MG-ADL score for a complement inhibitor, had a QMG of 12 in their screening criteria. Even if we just pick 10, we are pretty confident we will see significant efficacy, potentially superior or better than what we've seen with C5s historically. As we look at our phase three trial, we're going to be discussing with the FDA. We're looking to incorporate a once-a-month dose along with our every two-week dose of 300 mg, 2 mL. We're also looking to include a QMG of 10 or greater as a screening criteria in order to really shine a light on what this active C1s inhibitor could do in Myasthenia Gravis. I'm very confident that we won't see an efficacy difference between the Q2 week and Q4 week, and therefore Q4 week will be the dose we take forward to market. Potentially we could see improved efficacy over what complement inhibitors have been able to show to date. DNTH212, this is a very exciting bifunctional inhibitor that targets two validated pathways, BDCA2 in order to reduce type I interferon and BAFF/APRIL, which I am sure many of you are very familiar with. The idea here is to potentially provide superior efficacy or improved efficacy by going after two mechanisms of action, the innate and adaptive immune parts of the immune system in diseases where both these mechanisms are implicated in the disease. Either there is clinical data or there is a good scientific rationale for why taking this bifunctional approach would potentially give you better efficacy. We also have the YTE half-life extension on it. This will give us, we believe, dosing of every four weeks or potentially every eight weeks and making it a best in class also in terms of self-administration, subcutaneous potential autoinjector. Where are we in terms of milestones or what's next for us? We just delivered our phase two data. We just licensed DNTH212 from Leads Biolabs. Going into 2026, we will be announcing when we kick off the phase three trial and what the final design looks like and the length of the trial and so on, and when we would expect results from that program. Our CIDP data, we said we would have interim responder analysis announced in the second half of next year. We just moved that up to the second quarter. We will have that coming in the first half of the year. For MMN, our phase II trial, we will have top-line results by the end of next year for that phase II program. For DNTH212, we will be kicking off a phase one healthy volunteer study very soon. In 2026, we will also be announcing our prioritized list of indications for that program. We also raised money in September, so we have about $525 million in cash, which will take us well into 2028 and able to read out on all the milestones between now and then for both programs. Excellent. Thank you for that comprehensive overview. Of course, a lot going on, but one of the key focuses we are noticing now for investors is certainly CIDP. As you were saying, you have accelerated the interim responder analysis to the second quarter from the second half. That is quite impressive because historically we have seen from many sponsors usually delaying enrollment in an indication complex like CIDP. Even more recently, Sanofi announced that they are going to read out their phase three trial in 2027 and not anymore in 2026. Just curious, what operational strategies or other factors have helped you with enrollment? Yeah, so there's a couple of factors. First off, I do have to credit the team. The team's been very focused on implementation, execution. The track record we've had for the last four years, certainly since I've come in as CEO, has been exceptional. I'm very proud of them. We keep delivering on the timelines we say we were going to deliver on and, if anything, accelerate them. First off, kudos to the team. I think we've been hearing about delays in CIDP programs from our competitors for a while, whether it was Immunovant because they take patients and they make them relapse before they put them into part A or their trial. We don't do that. There's no studies in the future that I think are going to do that anymore. Physicians and investigators tell us very clearly they're much more comfortable diagnosing CIDP. There's no point making patients have to relapse before you put them into your trial to enrich the trial. We're not doing that. We're switching patients from IVIg, for example, or whatever they're on immediately to claseprubart, just like the phase II riliprubart trial did. They're open label. They switch patients from IVIg, for example, within seven days to active C1s inhibition, and still you saw really robust efficacy. There's no need to do that anymore. Also, we'll point out that with our trial, you only have to make patients come in every two weeks, not every week like riliprubart. We're taking all comers, whether you're refractory, whether you're stable on standard of care, or naive. You can come into our program. For riliprubart, for their two phase III programs, one, it's only refractory patients. The other one, it's only stable patients. Their pool of patients they can recruit are smaller. Finally, we have an open label part A. You know every patient you put into our trial is going to get drug. If they respond to it, it potentially could be years that they could be on drug with our study. If they do not respond to it, okay, then they move on and go to something else. Only those patients that respond then get randomized into the part B portion of the trial. That also makes it very attractive for patients. It makes it attractive for investigators. There are some inherently operational design advantages that we have. Again, I would go back to the team as singularly focused. We were focused on the MG program. The minute we were done with recruitment there, we put all our energy into CIDP and MMN. That, I think, also has a lot of impact. That is an advantage of being a biotech company versus a larger company. Look, we've been hearing about potential delays with other programs like the Sanofi program for a long time. This is not news to us because some of the investigators are the same. We just kept hearing that they're having trouble recruiting into other trials. This was not our experience. Certainly, when we put out our MG data in September, one of the first things we did is make sure that every investigator involved in all three of our neuromuscular programs see the data. What we heard very clearly from not just the MG physicians, but CIDP, MMN is, okay, this gives us a lot of comfort that obviously this works, but importantly also that it's very safe. I think that also helped accelerate some of the recruiting and screening into the CIDP program. That makes a lot of sense. Zooming in on the part A of the trial design, this is a two-part trial. Part A, you have removed the run-in period that was in the Vyvgart study. I think the original idea of that from Argenx was to enrich for very active patients. What are your expectations in terms of background characteristics of the patients that you will get in the part A? I guess, how can that affect eventually responder rate if there is any impact there? I understand why it was in the interest of FcRNs, which I think most people would agree are not going to be as effective as IVIg in CIDP, why you would want to remove the IVIg, make patients relapse, and then put them on the FcRN to enrich the trial. I would just point people to the phase II data from riliprubart, the active C1s inhibitor in Sanofi's pipeline. In their CIDP open label trial, they took patients and immediately switched them to active C1s inhibitor, riliprubart, within a week. There was no need to make them relapse to confirm. They just confirmed the diagnosis independently. Even without having to make patients relapse, you saw very robust efficacy to the point where Sanofi went ahead and designed a phase III trial that's going head-to-head versus IVIg. You don't do a trial versus the gold standard in terms of efficacy, standard of care in a disease unless you're really confident you're going to win. Not only did Sanofi do that, Argenx has taken their C2 inhibitor, which inhibits the classical and lectin pathway. Because it inhibits the classical pathway, should see efficacy. I don't know how potent it is, but they are doing head-to-head versus IVIg. They have the number one FcRn in the world, a blockbuster. They're not doing a head-to-head versus IVIg for that FcRn. They saw that data and they said there is something about classical pathway inhibition that potentially could deliver not just equal efficacy to IVIg in CIDP, but potentially superior. I think it's all based on this very robust efficacy signal you saw in the phase II open label trial with riliprubart. If they saw that, we expect to see the same in part A. Makes a lot of sense. We're doing the exact same thing they did. Yeah. Another important difference that you pointed out in your trial versus Argenx was that it's all comers. You will have SOC treated, naive, and refractory. What's your target for each of these, in percentage for each of these segments? What's the current status of enrollment for each of those? We do not have a target for each group. We are just taking all comers. I expect naive patients is going to be a very small percentage just because there are more therapies available now, et cetera. I think there will probably be the vast majority will be refractory or stable on standard of care. We are not providing any guidance on how enrollment is going today. All I can say to you is we have seen an uptick in both screening and prescreening and patients coming into part A. That is what gives us the confidence to move our guidance up to the second quarter. I guess your bar, it's like what we saw with Sanofi for the phase II? Yeah. I mean, look, at any point, depending when you looked at their data, it was anywhere from 40%-50% improvement on patients who are refractory or patients who are stable on standard of care, like IVIg. That range tells us that we're in the game. We're a more potent active C1s inhibitor. I think that's clear from the data we have that we've put out there and presented. The question is, do we have any additional efficacy? To me, similar efficacy with a much more convenient dosing and administration is a base case with an upside of potentially, if in CIDP, a better potency as an active C1s inhibitor can deliver better efficacy, then that would be the upside for us. Just quickly on the part B, have you already finalized whether the primary endpoint will be like a time to event endpoint? Exactly like Argenx. Exactly. Exactly. The differences between our trial and the Argenx ADHERE trial. One, we're not making patients relapse. Their 60%-65% response rate, that was from patients who had relapsed, meaning only two-thirds were able to get back to where they were before their treatment was removed. The bar for us is riliprubart, which is immediate switch, no relapse required. Secondly, we're allowing refractory patients into our trial. No FcRn will allow refractory patients into their trial because if IVIg didn't work, for example, it's very unlikely FcRns are going to work. As you saw from the riliprubart data, refractory to IVIg patients still had a 50% response rate on active C1s inhibition. It makes sense for us to include those patients. Those are the two biggest differences. Otherwise, it's pretty much similar. Basically, you have improved efficiency and increased the pool. Exactly. Exactly. Okay. Obviously with Vyvgart, we have seen that the opportunity in CIDP is even larger than what expected. How are you thinking about positioning? In CIDP? In CIDP. In CIDP, there's a potential here for a paradigm shift. I mean, if MG in our phase III trial, if we deliver better efficacy than C5s, if we get to a three-point difference on the MG-ADL like we saw with our post hoc analysis, that could be a game changer in MG with superior efficacy to what's been seen before, certainly in the complement class. In CIDP, if Sanofi's head-to-head versus IVIg and Argenx's head-to-head for claseprubart versus IVIg, if they prove to be superior to IVIg, then you will have a situation where classical pathway inhibition or active C1s inhibition will be seen as the gold standard in efficacy. IVIg will be seen as the second best option and then FcRNs third. There's a potential here for active C1s inhibition and certainly for classical pathway inhibition to completely change the treatment paradigm in CIDP. If you talk to treaters, neurologists, CIDP specialists, they'll tell you IVIg has been a lifesaver. If you talk to patients and neurologists who listen to the patients, they'll tell you they hate it. They say it changed their lives. It saved them, but they hate the administration. They hate the side effects. They hate the quality of life surrounding when they're dosed the IVIg or Ig. If you could deliver something that has better efficacy, but is a lot more patient-friendly from a side effect potential, from a delivery perspective, dosing administration, you'll really completely change the dynamics of that market. That is where I think what the opportunity is for clecipobar and CIDP. Perfect. Going back a little bit on what you presented at the beginning. At AANEM, you had pretty interesting new data. I was compelled by the new in vitro data where you showed that with blocking with C1s, you are able also to block C3a, C3b that have pro-inflammatory action. I wonder, both in MG and in CIDP, what do we know about this cytokine involvement? Is there any expectation, let's say, with longer trial duration to see any effect, let's say, higher than with C5 inhibitors? Look, this data, this post hoc data that I showed you earlier, where if we had had a QMG of 10 or greater, if we had had that in the trial, we could have potentially seen a three-point difference on the MG-ADL from placebo. The reason to believe that we could have that much more efficacy than what's been seen with C5s in the past is because of the upstream versus downstream inhibition piece. It is all about these pro-inflammatory split products, C3a, C3b, that are created and deposited right there at the neuromuscular junction between when the classical pathway is triggered and when a C5 shuts down the complement system before the MAC. The MAC is still the primary source of damage being done. C3a and C3b, logic tells you these are pro-inflammatory toxins, and they're right there, and they're constantly there for a patient who is HCHR positive and are on C5. We eliminate that. We clearly show that in our in vitro experiment that was presented at AANEM. That is the reason to believe why we may have better efficacy in MG than C5s. If you look at our baseline characteristics in the phase II trial, our QMG was only about 12 for the two active arms. It was 14 for placebo. That's a little low compared to historical data. That's why we said, let's look at what if we had had a QMG cutoff. You can see these results. It's the upstream versus downstream inhibition. That's the reason to believe why we could deliver better efficacy than C5s and MG. That is also very likely why you see efficacy in CIDP and MMN with upstream inhibitors, and you haven't seen it with C5s in the past. There may be something about this that's at work here. We've always known this was a potential benefit. We didn't want to present any data until we saw the MG data. Now that we see this, the logic is there. The equation is ready for us to now take all these learnings, take it into phase III, and deliver. That's pretty exciting. Maybe in the last few seconds, just one last question on the MMN program. What are the expectations there? We know that Vyvgart, that in placebo part, there is the program, but what's your bar? I really appreciate you bringing up MMN. MMN sometimes gets a little bit more of a bigger market than, MG, CIDP. But MMN is a smaller market, but it is one that is untapped, one where FcRNs do not work. There is only us and empasiprubart. Empasiprubart is a C2 inhibitor. It showed great efficacy. We should have similar or better efficacy because we believe we have a more potent inhibitor of the classical pathway. It blocks the lectin pathway, which does not add any real benefit. It is only going to add an infection risk, likely leading to a box warning. It is an IV. Again, we are aiming for one shot every two weeks, self-administered autoinjector. It is a smaller market, but it is one where we can get a bigger pie, piece of the pie. It does not take many patients in MMN to get to a billion-dollar potential in that market. Layering that on top of CIDP and MG in the same neuromuscular market, we are very excited. We are expecting data from that phase II by the end of or by the second half of 2026. There is already a precedent with the phase II data from empasiprubart. That is what we will be comparing ourselves to. Excellent. Thank you so much, Marino. Thank you. Really appreciate it.