Dianthus, Marino Garcia, who's with us today. We're going to do a fireside chat format. Thanks for joining us today, Marino. Thank you, Maury, and thank you to Jefferies for the opportunity today. Maybe to start off, if you want to give a one-minute intro to Dianthus, to those who may not be familiar with the story. Sure, so g ood morning. Dianthus was formed in 2019 to develop what we call next-generation complement therapeutics. Our lead program is an example of what we mean by next generation. 103 was designed to be a very potent, infrequently self-administered autoinjector or a subQ injection complement therapy to treat various conditions like myasthenia gravis, our lead indication. In 2022, we came out of stealth mode with a $100 million Series A, and started building the team toward entering our phase I trials later in 2022. In 2023, we reverse- merged into Magenta Therapeutics and went public in the fall. At the same time, we disclosed our phase I data, which pretty much confirmed what we had hoped, that DNTH103, an active C1s inhibitor of the classical pathway, was indeed very potent and with a very long half-life because of the YTE half-life extension modification we made to the FcRn region. We also were able to confirm that dosing every two weeks, so a Dupixent-like dosing administration profile would inhibit the classical pathway in a very powerful way. In early this year, we announced a $230 million PIPE, and started our phase II program in myasthenia gravis immediately after. We later in the year started our MMN program, multifocal motor neuropathy, our second indication. Just a couple of weeks ago, we announced that we are going straight into a phase III pivotal trial program with our third indication in CIDP. Great. Yeah, it's a great intro. W anted to start off with CIDP. You did just recently announce that you're moving into this phase III study, which you plan to start by the end of this year. Maybe talk about how the recent update expedites timelines, and could streamline investment for this opportunity for CIDP? When we were looking at our options for CIDP, I was actually quite impressed with what Argenx did with their ADHERE program. T he big question for me in terms of how they designed their program is, how would the FDA react? What would be the indication they would get when approved? W hen we saw at the end of June that they were approved for a very broad all adults with CIDP, it became clear that that would be our preferred option. It's not so much about saving time. It's about executing on one trial, one program, and really increasing the probability of success to about as high as it can possibly get in biotech. Essentially, what we're doing is, it's a one phase III pivotal program. We have two parts to it. Part A is an open-label trial where we take patients who have confirmed their diagnosis of CIDP, take them off IVIG, very likely they are on IVIG, immediately put them on DNTH103, 300 mg every two weeks after a brief loading dose. Only those patients that respond in part A, which is up to 13 weeks, so open-label, only those that respond to DNTH103 are then randomized into a placebo-controlled part B. We think that's really the best way to go about trying to get to a successful BLA and CIDP. Got it, s o it's a good overview of the trial. C an you talk more about how that compares and contrasts versus Argenx and Sanofi for their phase III studies? Sure. Versus Argenx's ADHERE trial, there are two main differences. One is, they did have a run-in period where they took patients off IVIG and let them deteriorate as a way to confirm that they have CIDP. I think that presented probably some recruiting challenges. Certainly with Immunovant, I think they put out an announcement where they had to delay their readout, because of the challenges around recruiting patients. That's not something really patients and physicians are very excited about, s o we don't have that run-in period. We basically just have an independent review board that confirmed the patients have CIDP, take them off of IVIG, but very quickly then put them on DNTH103. W e don't let them deteriorate before we put them on drug, and we also will allow patients who are refractory to IVIG into our program. ADHERE did not allow patients who are refractory to IVIG, which makes sense. They have a very similar mechanism of action. You wouldn't expect necessarily an FcRn inhibitor to work on patients where IVIG didn't work, but as we saw with riliprubart, Sanofi's active C1s inhibitor, with their phase II open-label program, they saw a very robust efficacy in patients who were refractory to IVIG and patients who were actually stable and doing fine, and switched from IVIG to their active C1s inhibitor. In both cases, they had over 50% response rate, so we feel very confident that we should allow both those patients as well as treatment- naive patients into our program. That's the difference with our Argenx's ADHERE. Sanofi announced two phase III blinded trials and randomized placebo-controlled trials. I n one group, they're going after IVIG refractory patients and looking for superiority over placebo. Then the other, they're going against IVIG in a non-inferiority trial. We're not going to do two separate trials. They need two separate placebo-controlled trials. It's their first indication. T heir phase II was open- label and not placebo-controlled, s o it's clear they needed to at least have two trials for their first indication. Whereas, like I said, we're going straight into one phase III. Got it, t hat's helpful. Argenx's ADHERE study took about two years and nine months to enroll. Maybe talk about the size of your study, and just expectations for being able to enroll this study and get to data. Yeah. Later this year, we'll provide more guidance on the CIDP program, specifics on the trial design and when to expect readouts from the program, s o expect to have that before the end of the year. You know, the good thing about 103 is when you look at it objectively in terms of trying to recruit patients to come into your program, the fact that it's a simple 2 ml subcu shot every two weeks. There's no allowing patients to deteriorate, you're only going to put patients into the program, into the Part B who have actually responded on your drug, I think that's a very attractive program for a lot of patients to get enrolled into. I nvestigators are telling us that this is the way to do it to make sure we have a successful recruiting timeline. Y eah, sometime before the end of the year, we'll provide more details on those questions. Got it, o kay. Maybe one other question on the point. You mentioned that you could have a CIDP readout within the second half, 2027 cash runway guidance. Can you just elaborate on that and whether that assumes a part A readout or the final readout from the study? We reported we have about $343 million in cash, which takes us to the second half of 2027. That will allow us to read out the phase II myasthenia gravis trial second half of next year, the MMN phase II trial, which we've guided to the second half of 2026. As you said, within that time period, we will have some sort of readout from the CIDP program. I think it's fair to say it'll be from the part A, not part B. It won't be the final results. Got it. Any other milestones from the study that you're going to share with investors along the way that you can comment on now? Not yet, s oon. Sorry, Maury. No worries. O ne of the questions, just, is there going to be an opportunity to compare and contrast any early data from the study to Sanofi or our Argenx? D o you see more opportunity to differentiate in the standard of care treated, the refractory, or the naive patients? As you mentioned, you're going to have all three groups in the study. Yeah. Look, we'll be looking at all the typical efficacy scores in CIDP, including obviously INCAT in both part A and part B. How much we reveal before the end of the program, that's something we're working through. The FDA has some very strong opinions on how much you can share and it is one single pivotal program, so we want to make sure we do it right. A s I said, before the end of this year, we will provide a little more guidance to investors on what exactly to expect, the design of the program, timelines, etc. Got it. C an you just talk about the opportunity a little bit too, just the proportion of patients that are refractory or responsive to IVIG? Y eah, is there more [audio distortion]? Yeah. I mean, look, there's not a ton of data out there, but when you talk to KOLs, there is this impression that IVIG works quite well. O ne of the big questions was, how is Argenx going to do when they launch? T he fact that they've had really excellent uptake, it's no surprise. They just have done incredibly well with efgartigimod. W hen you think about efgartigimod versus or an FcRn inhibitor versus IVIG, again, similar mechanism of action, so you expect similar efficacy. The issue with IVIG, is it's quite burdensome. It's really not very patient-friendly. The side effects are awful. T here's a huge opportunity within CIDP with every patient, certainly the moderate to severe patients, where they are definitely looking for something better. U p until now, again, IVIG has been the standard. That's what KOLs like. A s you know, with all these markets, once you have better options, more patient-friendly options, there's just a tremendous amount of opportunity within the CIDP market. The interesting thing as well is, just like MG, it seems that the market is growing just as there's more attention, more awareness, more prescribing, more trials. You're seeing just the number of diagnosed patients moving up, and now to the point where I think our latest estimates are more than 40,000. There was a recent study published that said it could be up to 58,000 just in the U.S. We 're very excited about the CIDP program. Myasthenia gravis is still the biggest commercial opportunity. That's still where there's a tremendous amount of impact still, that we can make in younger, less severe patients, w here complement therapy is still being used first line. We see that with the C5 inhibitors, and then MMN is one where we're also very excited. That is a smaller market than the other two, but it's one where FcRNs don't work. E ssentially, i t's a complement-only market, and there's only one other complement therapy being studied in MMN right now. It's empasiprubart, a C2 inhibitor, so all three of these markets just offer a tremendous amount of opportunity for 103 and Dianthus. Got it. M aybe last quick question on CIDP, just with moving into a phase III study, I don't know if there's anything more you could say about just alignment with FDA, and whether there's still some moving parts with the study design too or if everything's finalized? We are almost finalized. T hat's why we're saying we'll reveal more of the details before the end of the year, b ut we definitely have alignment with the FDA. Otherwise, we wouldn't have felt comfortable putting it out yet. We just wanted to make sure investors knew that we have this alignment, that we are going to one pivotal phase III program, that that is different from MG and MMN. I t's not a phase II. It won't be two studies sequential to each other, as we're seeing with the other two indications. Like I said, I think just before the end of the year, certainly. T hen before J.P. Morgan, we'll reveal more on CIDP. T hen before J.P. Morgan, we'll also provide a little more guidance on when exactly we'll see MG data in the second half of next year. Got it. Okay, h elpful. F or myasthenia gravis, let's talk about that phase II study. You've guided to having the top- line data in the second half of next year. Y ou plan to narrow the guidance to a specific quarter in early 2025. What's the latest status on enrollment? I s there anything notable you can comment on in respect to the types of patients that you're enrolling into this study? Enrollment's going according to plan, so we're still guiding to second half of next year. That's not changed. We're seeing exactly the kind of patients we expected to see, very similar to what you've seen in other phase II programs. W e continue to guide to, what we're expecting is efficacy very similar to other complement therapies. Certainly, like I would look at the Ultomiris study, a high one, so 1.7 say, so between 1.5 and 2 point difference on the MG- ADL versus placebo. Y eah, I'm excited to provide a little more guidance on when exactly we'll see that phase II data next year. It's going to be a very important year for Dianthus. Got it, a nd just for the study on ct.gov, it lists about 30 sites up and running. Have you had to optimize site selection and maybe just talk about that experience overall, or has it been pretty uneventful? It's been pretty uneventful. The expected ups and downs of trying to initiate sites around the globe. Yeah, the team's just doing a phenomenal job executing. Again, I remind people that we have a team that has experience in autoimmune, has experience in myasthenia gravis. Our head of clinical operations was with me at another company called Aspreva, where we were conducting an MG trial 20 years ago. This is not something that the team's not already done a few times before, but so yeah, everything's going according to plan. Got it. A lso, wanted to ask a question too. You mentioned the phase I data that you had in healthy volunteers. Can you just talk about how that compares and contrasts with Sanofi's riliprubart, which is the same mechanism of action? Just, I don't know if there's any perspective on that you can share. Yeah. In our corporate deck, there's a slide that we introduced in late June, where we conducted six different in vitro experiments looking at the potency comparison between the two molecules. T he reason we did that is exactly for that question. Almost every investor meeting I was in, we would get asked, what are the differences and why do you think you can dose so much less and less frequently than riliprubart? Beacuse t heir phase II and their phase III is dosing 600 mg, 4 ml every week. If you think about it in an auto injector, it would be giving yourself two auto injectors, excuse me, every week versus what we saw from our phase I data, that if we just get one 300 mg, 2 ml shot, which would be one auto injector every two weeks, our steady state is significantly above, somewhere around 40% above the levels we need to target to get 90% inhibition of the classical pathway, which is considered very strong inhibition of the classical pathway. W e did these experiments, these in vitro experiments, so we put them all on one slide. W e let folks decide which assay, which experiment they think is the most valid, b ut they all show very clearly in a head-to-head, same laboratory, same reagent, same person. Most of these experiments also conducted independently at another lab outside of the company, to make sure that what we were seeing was consistent with what they saw. Y ou can see we're multiple times more potent as an active C1s inhibitor, which allows us again to give less drug less frequently. I t's really going to be I think the main differentiation between us and riliprubart, aside from the fact that we are also going into MG and MMN, assuming both are proven CIDP. I expect that the main difference will be essentially dosing and administration being much more convenient with 103. Got it, t hat's really helpful. Y ou said, and so part of 103 is that you have to do a loading dose that's IV initially. Is there a potential to replace the IV loading dose with subQ dosing at some point? C ould you explore just getting more data on that and what could that look like? Yeah. The team's very focused on developing the device. It's going to be like a combination product, right? It's a device with 103, and introducing that at some point into the phase III program and conducting whatever other studies. There's multiple ways to do it, to show that a certain amount of IV is equal to a certain number of shots. I think what I tell people, we're aiming to have only subQ shots. Now, once I get a chief commercial officer, if they tell me they really want to have an IV option as well, then maybe we'll change our mind. R ight now, I envision the label exactly this way. Take the Dupixent dosing administration part of their label. Combine that with the efficacy, I'm talking about myasthenia gravis, of Ultomiris, C5. T hen take the safety and tolerability of another, the C1s inhibitor, the one C1s inhibitor that's actually approved out there, Enjaymo or sutimlimab. It's approved for cold agglutinin disease. I t's the only complement therapy on the market that has no box warning around any safety issue. Despite the fact that they're giving 6.5 g-7.5 g of antibody every two weeks by IV, it's a really favorable safety and tolerability profile. Y ou take the dosing and administration of Dupixent, the efficacy of Ultomiris, and then the safety and tolerability of Enjaymo and combine that into one label. That's what we're aiming for at the end of the day. That's our target product profile. Got it. Yeah, that's a great way to think about it. I wanted to ask about just kind of a mechanism question. With 103, it's going to be the first complement inhibitor to show MG-ADL data that shuts down classical complement activation at the initiation step. Based on this mechanism, how do you expect 103 to perform versus C5s on efficacy and safety? W hat kind of KOL feedback are you getting on this approach? What we're guiding toward is reminding people, this is a 12-week study. I f there's any differences in efficacy, it's likely only to be seen over longer term, over maybe the open-label extension, for example. W here we're guiding toward is, expect efficacy somewhere in the range like of an Ultomiris, so like I said, 1.5- 2, let's say. T he last C5 inhibitor, complement inhibitor to be approved is Zilbrisk. I n their phase III, and you see in their label, they achieved a two-point difference on the MG-ADL, so that is significant and obviously led to their approval. What I want to remind folks, is the biggest difference between us and a C5 inhibitor, or sorry, 103 as a classical pathway inhibitor that targets active C1s only, and a C5 is around safety and dosing and administration. On safety, we don't touch a lectin or alternative pathway. We're highly selective for the classical pathway. That's the pathway that's implicated in MG patients, for example, who are AChR positive. By leaving the lectin or alternative pathway, you're leaving the complement system to do what it's supposed to, which is help fight against the risks of infections from encapsulated bacteria, things like meningitis. That's why you see Enjaymo as a C1s inhibitor with a massive amount of antibody given every two weeks, but no box warning around the risk of infections because it leaves the lectin, and the alternative pathway intact to do what they're supposed to do, to help protect you. T hat's a risk that's certainly reduced with a C1s inhibitor. T hen like I said, the dosing administration, which I've already talked about versus an IV and patients having to go in, or seek the help of a healthcare professional to administer their medicine. This is something like again, patients can keep it in the fridge, take out, have it room temperature for a week or two, travel with it, give it to themselves over a five to seven second shot, and done. I think those are two main differences. W e fully expect the phase II program to reaffirm certainly the safety profile. Got it, a ll makes sense. L et's shift gears, talk about MMN, just maybe comment on the strategy there and just the opportunity as well. D o you think that a potential launch from Argenx, their EMPA and MMN could benefit 103's commercial opportunity, o r how do you anticipate that playing out? Yeah. I mean, in any of these conditions, if you're not first to market, you want to be the best in class and come behind a company that has the resources to really develop a market and educate. W ithin MMN, the good news there, it is a small market, but FcRNs don't work. It's IgM driven. We know that. It's classical pathway- driven. We know that, also confirmed by the Argenx team. T hey have Empasiprubart, which is a C2 inhibitor ahead of us. The challenge with the Empasiprubart is, it is an IV every week or every two weeks, and it does block the lectin pathway. By touching or blocking the lectin pathway, which really doesn't provide any benefit for MMN patients, because again, it is a classical pathway- driven disease, there is that potential risk for higher risk of infections and very likely end up with a box warning, as we see, for example, with alternative pathway inhibitors and C3, C5s, etc. For us, the big difference there is, although we're behind them, is that we'll be able to avoid the box warning. Because their efficacy you're seeing in MMN is actually quite significant and is driven by their blocking of the classical pathway, which is what we target, we expect to see similar efficacy. The question really is, how potent of a classical pathway inhibitor is Empasiprubart? We haven't seen data that tells us how much of the classical pathway they're shutting down, what percentage of inhibition that they're achieving. We know from our data that we get over 90% inhibition with 300 mg every two weeks. A t some point, it'd be great to see the PK/PD data on Empasiprubart, so then we can compare and set expectations on what level of efficacy we might see. Got it. Maybe just talk about your ongoing study, how that's going, and just assumptions around timelines for the study as well. Again, we just initiated that study in the summer, and that is going according to plan. W e're still guiding to the results of that phase II program in the second half of 2026. It's a smaller study than MG, but it is a little longer and it is a rare disease, so a little tougher to recruit. T hat's why we're giving ourselves an extra year to read out that data, b ut everything's going according to plan with that one as well. Got it, o kay. W e've talked about CIDP, MG, and then MMN today. Are there other expansion opportunities you could pursue, and what are some of the deciding factors that go into that? Yeah, there are other indications. M uch like how we decide on MG, MMN, and CIDP, if we're going to add new indications, we're looking for those new indications to be able to overcome two major hurdles. One is, is there clear proof of concept and biological rationale where we feel very confident it'll work? S econdly, is there a very clear unmet need and commercial opportunity where 103's differentiation could really make a difference in patients' lives? T he team's working through those options and ideas. I f we do expand into other indications, because there are quite a few places you could go with a classical pathway inhibitor, we'll probably announce that a fter the MG results. Got it. Marino, this is a great conversation. We covered a lot. Maybe just in closing, if you want to highlight key catalysts that investors should be focused on. Yeah, before the end of this year, we'll provide more details on the CIDP program. Certainly, by J.P. Morgan and other meetings somewhere else, we'll provide data guidance on when exactly in the second half of next year we'll see MG data. T hen of course, second half of next year is going to be a really critical moment for the company, where we finally have data in actual patients. Got it, l ook forward to it.