Welcome to our inaugural Healthcare Innovation Conference. Our next presenting company is Dianthus. We have a few executives from the company here in the room. But with me here on the stage is the Chief Executive Officer, Marino Garcia. Marino, why don't I hand it over to you? Maybe you know, give a five-minute overview on the company, your upcoming catalyst, and then we'll go into the fireside chat session. Sure, thank you, Yatin, and thank you to Guggenheim for the opportunity to participate in your conference today. So very pleased to be here and provide an update. Dianthus Therapeutics was founded to develop what we're calling next-generation complement therapeutics, and our lead program, DNTH 103, is a perfect example of what we mean by that. It's an active C1s inhibitor that was developed to be a highly potent inhibitor of the classical pathway, leaving the lectin and alternative pathway intact, and to also be administered in an autoinjector in a very patient-friendly, once every two weeks, one shot every two-week, schedule. 2024 has been a year of execution. In 2023, we went public and released our phase I data, which confirmed that we have a very potent classical pathway inhibitor, and that could be dosed with one shot every two weeks to significantly shut down in a very powerful way the classical pathway, with a potentially differentiated safety profile versus other complement therapies. So confirming its potential as a best-in-class complement therapeutic in conditions like myasthenia gravis, MMN, and CIDP. So this year, as I mentioned, is a year of execution. Earlier this year, we started our phase II program in myasthenia gravis. Mid-year, we started our MMN phase II program, multifocal motor neuropathy. Just last week, with our Q3 earnings release, we actually announced what I think is some very good news, which is that we are not initiating a phase II program in CIDP, but actually a phase III pivotal program before the end of this year. It's a. We have agreement with the FDA. It's a two-part phase III program. Part A is an open label where we take CIDP patients and put them on 300 mg every two weeks. For those that respond, they then get randomized into part B, which is a placebo-controlled study. As I said, we're looking to initiate that program before the end of this year. Got it. Very good, helpful. So maybe just drilling a little bit deeper into the CIDP, could you put number one in perspective what we have seen with this mechanism that gives you confidence that this is a viable mechanism in CIDP? And then we'll discuss the study design a little bit. Yeah, there are two studies or competitors that we watch very carefully over the past year to inform how we would approach CIDP. First off is Riliprubart. This is an active C1s inhibitor in Sanofi's pipeline. A year ago this month, they disclosed interim phase II data in CIDP that was really quite impressive, and they've continued to update that data, including the latest update was at PNS at the end of June, where they saw really strong efficacy, impressive efficacy in three patient groups in CIDP in their open-label phase II program, in those patients who were treatment-naive to IVIG, patients who were refractory to IVIG, and patients who were stable and switched to active C1s inhibitor. And again, they saw very strong efficacy across those three groups. So those are the three groups we will be looking to recruit into our program. And then we also were looking obviously at the ADHERE program from Vyvgart or from, sorry, from efgartigimod from argenx. And that was a highly enriched randomized withdrawal program. And what we were curious to see is how the FDA would look at that data and what kind of label they would get. And at the end of June, we saw them get a very impressive approval for all adults with CIDP. And so at that point, we made the strategic decision to take the same approach, which is go straight into a phase III randomized withdrawal design like ADHERE. The two big differences between our program and ADHERE, one is we won't have a run-in period where we test to see if patients do need IVIG by removing IVIG. That has caused some enrollment issues for our competitors. And in [MG], most recently, we don't have that in our design. And we will be including patients who are refractory to IVIG, which ADHERE did not. It makes sense they wouldn't. FcRns, IVIG, very similar mechanism of action. So if IVIG doesn't work, you wouldn't expect FcRns to work. But with our active C1s inhibitor being a different mechanism of action, we saw that in the Sanofi phase II data, patients who were refractory to IVIG switched to active C1s inhibition. Over half of those patients improved. That's a really, really robust response rate. So we are definitely including those patients in our program. Got it. So these two key differences, right, by not having that run-in, does that introduce additional risk? Because, you know, in general, the diagnosis is not straightforward for these patients. We will be obviously training our investigators to identify the right patients, but there will also be an independent review board that will confirm whether these patients have CIDP. So we're taking that risk off the table, and like I said, and then these patients will be put on, and it's an open-label part A where they'll be put on DNTH 103 every two weeks. Only those patients that respond will then be randomized into the next part. That's up to 13 weeks. Up to 13 weeks. Okay. The fact that you are going to have a refractory patient population in the study, does that mean that the study's design is going to be appropriate to show a benefit in that defined patient population? So likely bigger than what argenx conducted? We do have in the protocol the ability to analyze these subgroups. At some point, we would release data to show how 103 performed in those three different subgroups. The treatment naive, treatment stable, and switched, as well as refractory to IG. By the way, we'll include IV as well as sub-Q IG patients. When should we anticipate you disclosing more details, you know, including the phasing and other details for the study? Yeah, we had our Q3 earnings release, and of course, we couldn't say that we were starting a phase II at that point because we have agreement with the FDA. We know we're going into a phase III. That's why we released that last week. But before the end of this year, not too distant future, we'll release more details about the program like we have for MG and MMN. Okay. What about the enrollment timeframe? Anything you are willing to articulate now? Just trying to understand when should we get the data? Sure. So, we're not disclosing that at this point, but what I can say is we have a cash runway that takes us to the second half of 2027. And we will have data readout for MG and MMN within that timeframe. So second half of next year for MG, second half of 2026 for MMN. And we will have, you know, some kind of report out from the CIDP program within that timeframe. Got it. I think you have done some head-to-head analysis versus the Riliprubart. Could you just articulate what were the learning for us? You know, what gives you confidence that your antibody is even superior to, Riliprubart? Sure. Yeah, we were surprised to see the dosing for Riliprubart way back when, you know. They're dosing 600 mg every week, which is four ml, which is, if you were to put that into an autoinjector, that would be like two autoinjectors every week. Correct, yeah. And so we are aiming on our target dose, as I mentioned, is 300 mg, two ml, one autoinjector every two weeks. So at the end of the month, it would be eight autoinjectors for Riliprubart versus two autoinjectors for DNTH 103, which is a significant improvement in terms of patient convenience. So the question has always been, well, what gives us the confidence that that we're going to have that kind of differentiation from a dosing and administration? There's two things that give us the confidence. One is we know with 300 mg every two weeks, two ml shot every two weeks, we get significantly above the IC90. We get very strong inhibition of the classical pathway, over 90% inhibition of the classical pathway. And you can see that we modeled that out in our corporate deck. but to really provide more confidence, especially for investors, that, you know, we have the right dose and we will be able to achieve that kind of differentiation, we conducted six different, head-to-head in vitro experiments, looking at potency as well as an inhibition of the classical pathway, affinity assays and enzymatic assays, et cetera. And again, you can see that in our corporate deck. And these were head-to-head in the same laboratory using the same reagents. And we also had most of these experiments conducted by an external third party just to confirm that the data we were seeing is correct. And it's very clear that we have a significantly more potent active C1s inhibitor than Riliprubart. On the CH50 hemolytic assay, which is the assay that we believe is the most relevant, we are seven times more potent. So it's very consistent. The orders of magnitude more potency is clear, and that just translates into that we can give less drug to achieve the same level of inhibition for the classical pathway, so that's what gives us that kind of confidence. Got it. What are some of the safety considerations for this pathway? The nice thing about only inhibiting the classical pathway and leaving the lectin and alternative pathway intact is that there is a potential for lower risk of infections from encapsulated bacteria, so things like meningitis. If you look at complement therapeutics that are approved today, whether it's a C5 inhibitor, a terminal inhibitor like ULTOMIRIS, C3 inhibitor like EMPAVELI, an alternative pathway inhibitor like iptacopan, they all have a box warning around the risks of infections from encapsulated bacteria and an associated REMS program. There is only one complement inhibitor that does not have any box warning or any REMS program around any safety issue. And that's ENJAYMO or sutimlimab. It was Sanofi's C1s inhibitor, first generation C1s inhibitor, but it's now been sold to Recordati for $1 billion. It was announced a couple of weeks ago. But, if you look at their label, they are a C1s inhibitor approved for cold agglutinin disease, and they have absolutely no boxed warning for any risks or any safety issues. That is a very strong differentiator. And so, that is going to be our goal is to achieve that kind of a safety and tolerability table. So how does, so then maybe talk about the positioning, thinking or, you know, considering that the FcRn are already there, you're going to be there, let's say 2028, 2020, whatever, like 2028, 2029 timeframe. Where do you think this mechanism fits, once you are in the, once you are in patients? Once you are approved. With MG and CIDP, it's going to be the exact same market dynamic. There's going to be only two classes of biologics competing for first line use, and that's FcRn and complement. Our goal is to simply be the best complement inhibitor, and so that if a physician and patient decide they want to start with a complement inhibitor, that we be the first choice. If for whatever reason a patient was started on FcRn first, whatever you believe the best FcRn will be at that point, and like in every autoimmune disease, patients switch all the time, we should be the first switch. That is our goal, and if you look at within the MG market, every single complement inhibitor that's approved or in development is a terminal inhibitor, is a C5 inhibitor, so it's just one form or another of a C5 inhibitor. Therefore, we'll all have boxed warnings and none will have the dosing administration convenience that 103 would likely have, potentially have. If you look at the CIDP market, there's Riliprubart that will be ahead of us. But again, we've already, I've already talked about the dosing administration that will be a big differentiator that's a direct result of our having a much more potent active C1s inhibitor. But it'll be the same situation there. And what's interesting with our argenx is, obviously they're approved for CIDP with efgartigimod, but they also just announced that they're taking their C2 inhibitor, a complement inhibitor, into CIDP as well. So they acknowledge that these are the two classes that are going to compete. That's, there's really nothing else that we see in the pipeline that could compete as a first line targeted biologic in either of those markets. And I'll just let me put in a little plug for MMN because sometimes it doesn't get as much attention. It is a smaller autoimmune market, but that is a clear classical pathway driven disease. And the attractive thing about MMN is although it is smaller than CIDP and MG, FcRNs don't work. And so it's a complement only market. And really there's only one other product and that's Empasiprubart from argenx that's ahead of us. And that is an IV that's given every week or every two weeks. And because it's a C2 inhibitor, it also blocks the lectin pathway, which is a critical pathway for fighting against the risks of infection. So I would fully expect that they would get a boxed warning, much like the alternative pathway inhibitors, C3, C5, et cetera. So again, we could have a much, a very differentiated, better option for patients in MMN. And that's it. There's really nothing else that will compete in that market aside from complement therapeutics. What is the size of that market? How many patients? So right now we're estimating it's somewhere from five to 10,000, but I fully expect like MG has grown over the years as people get more familiar with the disease and the incidence and diagnosis numbers have gone up. CIDP, I mean, just maybe a year or two ago, estimates were somewhere around just north of 10,000. Now we're seeing from claims data from IQVIA that it's north of 40,000. There's a study just published that looked in the U.S. and said the estimate could be as high as 58,000. So the numbers are growing. And I fully expect as more attention is placed on MMN or multifocal motor neuropathy, that we will see those numbers continue to expand as well. Got it. Let's discuss the MG study that you're running. But before we discuss the study, like what is the scientific evidence, indicating that blocking complement, just the classical complement pathway is sufficient? So for MG, you know, it's quite often in the literature referred to actually as a classical pathway driven disease. And for AChR positive patients, it makes sense. It's an AChR antibody driven disease. And within the complement system, that's what triggers the classical pathway. So it makes a lot of sense. And of course, C5s have been shown to be very effective in MG. So that's partly why we picked MG as a first indication. It's where the biological rationale is the strongest. That's where the clinical development pathway and regulatory pathway is the clearest. And that's where we can differentiate ourselves the most and become the best in class complement therapeutic for patients with AChR positive MG. And it's clearly the biggest commercial opportunity. It already supports multi-billion dollar blockbusters, even the C5s, which are significantly more expensive than efgartigimod. You know, AstraZeneca very clearly is saying that franchise continues to grow. They're over $6 billion, and that growth is coming specifically from biologic naive patients with MG in the United States. So, I think that is the biggest opportunity we have. Obviously, CIDP has gotten a lot of attention recently because of the data from Riliprubart, and again, MMN I think is also an underappreciated in terms of what the opportunity is for a strong, safer and convenient classical pathway inhibitor like ours. What are you doing in MG? Could you talk about the [MG] study? How many arms? How is the enrollment? When do we get the data, and what would you like to show? With MMN and CIDP and MG, we decide to test two doses, 300 mg every two weeks, which gets us significantly above the IC90, or 90%, above 90% inhibition of the classical pathway, which is very strong. We're also testing double the dose to get way up there above IC95, like completely shutting down the classical pathway. Just to answer the question, what happens if you get up higher? I don't think we're going to see a difference in efficacy. We wanted to test both of those. Those are the two phase IIs we started, and those are ongoing and according to plan. For MG, enrollment is going according to plan. Like I said, we continue to confirm that we will have data by the second half of next year and certainly by early January. I won't mention whose conference. We will provide a more specific timing around when we'll see MG data in 2025, and MMN, like I said, is still on track for data by the end of 2026. Are you enrolling FcRn-exposed patient in that study at all? They could have been on FcRNs. They just have to have been washed out. Washed out. What would you like to show? Like, what does the success look like with you? To me, success in the MG program is to have similar efficacy to ULTOMIRIS. ULTOMIRIS in my mind is the gold standard in terms of efficacy. More and more in real-world with real-life data, we're seeing that, you know, long term, you know, complement inhibition with consistent dosing, with consistent inhibition of the classical pathway or the complement pathways, with consistent efficacy where you don't have patients cycling and having their MG ADL rebound and potentially causing more damage to the neuromuscular junction over time, that is the gold standard in efficacy. So that's what we're aiming for. Something similar to what we've seen with the C5s, specifically ULTOMIRIS. What endpoint is it? The MG-ADL, which is about a two-point delta is, you know, can take. Yeah, anywhere in the high ones, so 1.5 to 2, low 2s that would be, that range tells us, and different from a placebo, of course. Yeah, for that delta. that delta would be a success in our mind. Okay. Anything else that we should look at? Obviously, I understand safety, but what about MSC? You know, there is enough. There is emerging focus on complete resolution of symptoms. Is that? It's a small study? I mean, these are 12-week studies, the phase II studies. So, I think maybe in the open-label for longer term, we might see that, and certainly with the phase III being a larger trial, and that will be very similar in design, but we'll have also an open-label extended period, then maybe we can see that, but within 12 weeks, very hard to see that kind of data. At that point, like I said, we're just looking to see similar data to what ULTOMIRIS showed and demonstrated in their phase III program when they got approval. Got it. And it. And what would be the regulatory package? How is it going to look like? You would have to run one more phase III study, two more? The phase III study, yes, we have to run one more phase after the phase II. The phase III would look similar to the phase II, just larger numbers because then you want to have the MG-ADL as a primary endpoint. Likely one dose? Likely one dose, one arm. We'll see. Okay. Just a reminder, the phase II MG-ADL is a secondary endpoint. It's primarily safety and tolerability. It's a smaller trial. It is actually the largest phase II trial done with complement therapeutic and MG with 20 patients per arm. But, yeah, the phase III would be significantly higher, larger numbers so that the MG-ADL could be the primary endpoint. Got it. Any view you might have on the emerging mechanism within the MG? We are seeing CD19 coming in there. I think there is an oral C1s that somebody is developing. Just curious, like how are you looking at the competition and trying to be ahead of them? I'm not seeing anything that will change the dynamics I mentioned where you have FcRns and complement therapeutics as the first line, biologics and MG. I don't see anything in the pipeline that will change that. The IL-6 from Chugai, the UPLIZNA from Amgen, they, you know, I think the consensus is they were, the data was a bit disappointing. With UPLIZNA, I mean, it took almost six months for AChR positive patients to separate from placebo in terms of efficacy on the MG-ADL. That's a long time to wait for efficacy as well as, you know, not an easy safety table, as well. So I see these emerging other mechanisms as potentially being more like second line where FcRn or complement somehow doesn't work for an AChR positive patient in MG. Look, MG is known to be a classical pathway driven disease. I think having a laser-like potent antibody like we do that targets the classical pathway, going after activated C1s, leaving the rest of the complement system, leaving the B cells or Ig levels, everything else to be normal so you can continue to have a functioning immune system overall. I think that is rationally the best approach, and so if we can show the kind of efficacy we expect with the MG data in the second half of next year, I think it'll be very clear what is a best in class therapy for MG. So the data will speak for itself when we report it out in the second half of next year. Got it. So you already have a lot between MG, CIDP and MMN. Like how are you considering other indication expansion of the asset? The team's doing a lot of work to look at where else we could take a potent classical pathway inhibitor, like DNTH103. There are two hurdles. One is where is there proof of concept or very strong biological rationale, especially in humans for classical pathway inhibition only, you know, getting the kind of efficacy that we would look for. So that's one bar. And the other bar is where is there a very strong commercial opportunity where there's a significant unmet need that something like 103 could really satisfy. You know, on the first one, you could say cold agglutinin disease or ITP, but that doesn't pass the second bar. It's not a very commercially attractive market for us. So, I think once we identify those other areas that we could go into that overcome those two hurdles, then that's something we would announce very likely after we see the MG data. Very good. I think that's what I had for you. Thank you so much, Marino. Thank you. Appreciate it.