Conference Transcript - DNTH 2026-11-11

Alex Thompson, Analyst — Stiefel

Good morning, everyone. I'm Alex Thompson, a biotech analyst here at Stiefel. I'm very happy to have Marino Garcia, President and CEO of Dianthus Therapeutics, with us this morning. I'll hand over to Marino to go through a few slides with a quick overview of Dianthus, and then we'll get into a Q&A.

Marino Garcia, CEO

Thank you, Alex, and thank you to you and the Stiefel team for this opportunity to update everyone on what's going on at Dianthus. Just quickly, I will be making some forward-looking statements, so I urge everybody to go to our website and read our SEC filings for all the appropriate risks around investing in Dianthus. I'm just going to do a very quick overview of Classypivart and set the frame, frame the conversation we're very likely to have, especially around MMN. And our goal here for Clasipibart is to achieve a target product profile that would position Clasipibart as a preferred first-line treatment across all three indications we're pursuing, MG, CIDP, and MMN. And what does that mean? Well, first, we're aiming for best in disease efficacy, and I'll get into a moment how we will position the product that way. We're looking for differentiated safety as being the only complement inhibitor, potentially, in these markets without a box warning or a REMS program. And then, of course, delivering it in the Dupixin auto-injector, essentially, a 300-milligram, 2-milliliter shot, once a month in MG, once every two weeks in CIDP and MMM. And we see this as a huge opportunity where you look at all three indications together. Together, we're looking at over 150,000 patients with MMN being severely underdiagnosed and with the potential to really grow that market with more effective therapies being launched. So I mentioned we're looking for best-in-disease efficacy. What gives us the confidence that we potentially could have that? On the left here, you see how we would differentiate versus C5s in the MG space. With clasibivir being an active C1S inhibitor, a classical pathway inhibitor, an upstream inhibitor within the complement system, what we'll be able to do that C5s can't is prevent the formation of C3A and the deposition of C3B. Toxic, pro-inflammatory split products that are a result of the complement cascade, and all occur before C5s interrupt the complement cascade. These are causing inflammation and damage at the neuromuscular junction for MG patients, and we'll be able to prevent that. We believe that will result in a higher MG-ADL, potentially, versus C5s. This is the reason an active C1S inhibitor works in CIDP and MMN, and a C5 won't, Because these are the pro-inflammatory toxic byproducts of the compound cascade that cause the damage in CIDP and MMMN. And then on the right, middle and right, you see how we compare to two complement inhibitors in development for CIDP and MMN. Relipid BART, you see we have seven times more potency than Relipid BART. And versus Empacipid BART, in the same in vitro experiment they conducted in their own publication published last year, the Cadell Microview CH50, at the IC90, we're 38 times more potent. So we believe, at least in CIDP, it looks like we have better efficacy versus Rolipibart, and we'll have to see versus Mpacipart once they have their phase three data in MMM, and we have our phase three data in MMM. Speaking of MMN, we are expecting data from our Phase II in December. A reminder, this is a very small study. Originally planned to have only 12 patients per arm. In 2024, when we went to see the FDA, we would have loved to just go straight into a Phase III the way we did with CIDP because it will be a supplementary BLA, but there was really no precedent for what a Phase III trial would look like in this space, so we decided to do a small proof-of-concept Phase II study. We over-enrolled, which is great, so we'll have about 15 patients per arm. And we're testing 300 milligrams every two weeks and 600 milligrams every two weeks. We do not expect to see any efficacy difference between those two doses. Primarily, it's a safety study. I can tell you on a blinded basis that data looks very similar to MGM-CIDP, so we're very confident on that front. And then secondary endpoints will be things like grip strength, which we now know is the primary endpoint in a Phase III study. When we reveal our results, people will want to compare, of course, to ARDA, the phase two study from Argenix with M-Pacipabart, and I will just caution that there's one major difference between our study, the phase two study, and their phase two study. They made a big deal out of the 91% reduction in required retreatment with IVIG to rescue patients. Our protocols are very different on that point. In our trial, A patient has to relapse, has to have a documented clinical deterioration to get IVIG, and every patient who did have a clinical deterioration gets IVIG. If you did not relapse, you do not get IVIG, period. Very simple, and it makes sense. That's our protocol. But the protocol for ARDA, there are patients who clinically deteriorated and didn't get IVIG. There are patients who didn't clinically deteriorate but raised their hand and asked for it and got it. And so it is a very, very different protocol, and therefore it's not going to be possible to compare on IVIG retreatment. What I would say is safety is fair to compare, and then the secondary input on grip strength, very similar. We have a three-day average grip strength, as they did in phase two. That's fair to compare. And then just basically relapse rates. That's a fair comparison. But IVIG retreatment, we have completely different protocols. And I'm not going to be able to compare. So finally, just how do we compare in a bigger picture? How does clasipibart compare to empacipibart? Empacipibart is a C2 inhibitor. As you saw in the potency slide, we are much more potent in terms of shutting down the classical pathway using the assay they published with, the assay that they used to highlight their potency. We're 38 times more potent. They blocked the lectin pathway and the classical pathway. There is no way for the complement system to really react to the presence of encapsulated bacteria if you're shutting down both those pathways. We leave the lectin and alternate pathways intact. The lectin pathway is the main pathway that will be triggered by the presence of encapsulated bacteria. That will then rev up the alternate pathway. That will rev up the formation of MAC and then goes and lyses the bacteria. And that's what protects you from, for example, meningococcal infections. We leave the lectin-alternate pathways intact to be able to do that. So it's very likely they will end up with a box warning and a REMS program. And then finally, they're an IV, and we're a self-administered auto-injector every two weeks. The exact same one as Dupixin. Go to the Dupixin patient website, see how easy it is. That's what we're going to launch with.

Alex Thompson, Analyst — Stiefel

Great. Thanks, Marina. Maybe since we're talking about MMN, I kind of want to maybe start with a question around, And, you know, obviously the focus for you of the Phase II study is a safety study, right? But you will get some endpoints around efficacy. How are you thinking about what signals you might be able to see, and how does that impact your thoughts around moving into a pivotal study after this readout?

Marino Garcia, CEO

We're going to be looking at the same secondary endpoints in terms of muscle strength as Argenics did with their ARDA study. And now we know that grip strength is going to be the primary endpoint in Phase III. So those are going to be fair to look at. And what we're looking for is very similar to ARDA, just numerical trends. But I'll be honest with you. There's almost nothing that we will see in our phase 2 study will keep us from going into a phase 3 study. We know MNN is IgM-driven. We know that it's triggering the classical pathway. Argenix and Dianthus are 100% aligned on that, that it's a classical pathway-driven disease. And we shut down the classical pathway with one shot every two weeks. This is the highest unmet need of the three indications. IVIG is a standard of care, but it is not as effective there as it is, for example, in CIDP. Even patients who seem to respond to IVIG, their disease still continues to progress. There is a very high need here for something that works, that's stable, that's consistent, that's easy to self-administer, and certainly better tolerate with no-box warnings like IVIG. So no matter what we see in our study, we're moving forward to phase three. And frankly, no matter what Argenix announces with M-PAS CiproBart, we're moving forward with phase three.

Alex Thompson, Analyst — Stiefel

I guess maybe to that latter point, obviously we're going to get the M-PAS CiproBart phase three data around the same time. What are you looking for out of that study? You know, at all. Like, do you think it matters if they hit non-inferiority to IVIG or superiority? How does that impact your thoughts around ClosiproBart?

Marino Garcia, CEO

Again, because of the dramatic difference in potency between our two drugs, C2 is not a very good target to go after if you're just trying to shut down the classical pathway. It's a good target to go after if you're trying to shut down or at least modulate the classical and lectin pathways. And historically, I think Argenic said that, you know, that might be good for things like AMR or EM, but both those studies are no longer going on. I think the AMR study failed. So it is very difficult to really shut down the classical pathway by going after C2. So, as I said earlier, no matter what data they show, we're moving forward, and we think we can do better than whatever they show in their phase three, honestly. So if they show non-inferiority, fantastic. We think we may be able to get to superiority. If they show superiority, fantastic. That just tells you how weak IVIG is in MNN. We may be able to show even better efficacy and superiority versus IVIG. And if for whatever reason, I think this is a very low probability, because IVIG is not a very high bar. If they fail, we're moving forward, and non-inferiority or superiority is a win, and we get approved. Yep. How quickly could you move into a pivotal study here? I mean, it'll be as fast as we can. So here's the steps. One, we put, obviously, our data together to be ready to go talk to regulators, especially the FDA. Two, we talk to KOLs, especially those who might have been involved with their trial, and say, hey, what advice do you have for us based on your experience? What could we do better? What should we avoid? What lessons did you learn? And we'll take all that and propose our phase three to the FDA, have a meeting with the FDA, and get signed up and go as fast as possible. You know, we did that with Captivate, our CIDP trial. Same thing. We took ADHEAR, which I thought was a brilliant study, but we made improvements on it that would help with recruitment, that, you know, were more patient-friendly, and that would ensure the success of the trial, and then went ahead and executed that. And we'll do the same thing with the phase three with MMM. Okay.

Alex Thompson, Analyst — Stiefel

So maybe let's pivot back to the other indications, maybe starting with CIDP. You obviously shared your early interim update and then a more fulsome interim data set earlier this year, and things are progressing through Part A, and you've guided to full Part A data at the end of next year. I guess, can you walk us through kind of the progression of at least the decision-making to share more of this Part A data than I think initially maybe you had thought or we had thought as the stream?

Marino Garcia, CEO

Sure. So our goal in Part A was to have similar responder rates as what LipidBart did in their Phase II. Very similar design in terms of it being an open-label study. So we had, with our first 40 patients, we had a target of seeing 20 responders. So the moment we had 20 responders with, I think it was 26 patients had finished Part A. We decided, well, we should go ahead and announce, we've hit our target, like we know we have the right dose and we're gonna be moving forward. We didn't reveal the overall responder rate at that point because we didn't have 40 patients complete Part A yet. So that happened in March. And then later, around April, May, we had the 40 complete, and we saw that our responder rates was 75%. So that felt good. And we said, well, we hope we can sustain that kind of high level of responder rates as we move forward. And then June, we had Sanofi's news. And at that point, we had more than 40 patients completing part. And we saw that the numbers were not coming down. It was looking really, really good, and we felt it would be comforting for investors to know what that number is because we had confidence that we would be able to sustain it. I can tell you, to date, we're over double the number of patients, over 80, approaching 100, and those efficacy rates are right on the same zone. So we released that data to give people comfort that, you know, things are going very well. And it wasn't just the responder rates. Actually, the more important part of that slide we have on our deck is the table next to it because it shows you across different measures how dramatic the improvement of these patients, the kind of improvement we're seeing in these patients on class hyperbar. The question might be, well, why reveal all that? Doesn't that affect potentially bias the study of the integrity? Remember, the FDA really only cares about Part B. That's the blinded, randomized withdrawal part of the trial. Part A is simply just finding responders to your drug. And we're not biasing the study by revealing the responder rates because physicians are seeing it, the investigators are seeing it, they're putting these patients on drug, it's open label, and they're seeing the response rates and they're calling us and going, oh, wow, this patient used to be on a wheelchair, and on the second or third visit, they walked in on their own. So they know how it's working. What we didn't reveal is how are naive patients doing, how are refractory patients doing, how are standard-of-care stable patients doing, how are IVIG patients switched to our drug doing. The reason we don't reveal that, that could bias the mix of patients that then investigators go and try to recruit into our trial. We didn't want to bias that. So, for example, we have about 10% of patients who are naive. The naive patients were the ones who had the highest response rates. If investigators see that, if CIDP patients see that. All of a sudden, we could see that that number could increase to 15, 20, 25 percent of our patients at the end of the trial, and now that trial doesn't exactly look like what the general CIDP population would look like. So what we'll do when we're done getting 120 patients enrolled into Part B, that means the study is done, we shut down recruitment into Part A. Then we will reveal not just the overall responder rate again with the table, but then we'll share, how did the refractory patients do? How did the naive patients do? How did the standard care patients do, the stable patients do? How did the IVIG patients switch to our drug do? And then you'll have much more visibility, because at that point, there's no bias in the trial. We're done. There's no more recruiting. We're just waiting a year for Part B to finish. And everybody there is blinded, and we don't know what arms they're in. So there's really no regulatory risk. Revealing it in June was just to make sure that investors understood that, you know, we felt really good about what we were seeing and that the responder rates are significantly higher than what we had expected, certainly better than relipobards.

Alex Thompson, Analyst — Stiefel

So maybe pivoting to MG, could you walk through some of the major, you know, Differences between the phase two and the phase three and how that might impact both IMAs enrollment and then maybe the outcome in terms of, you know, the delta that you might see. MG, yeah.

Marino Garcia, CEO

So MG is a three-arm study. We are testing a new dose, which is 300 milligrams once a month. We always suspected that you may not need to be above 90% inhibition of the costco pathway to work in MG. And we saw from our open label extension that that looked like was the case, and then we saw some DISRAM data where they, in their initial press release, were very up front and said we only inhibit 75% of the complement system using a CH50 assay, and they had pretty good efficacy. So it makes sense for us to test once a month. Once a month for us, with classipibar, one shot, we'll get at least about 75% inhibition or higher. So it makes sense to test that. The other big change, it's an extra month because we have this once a month dose, so let's get at least one more shot in there. And then finally, in March, we filed an 8K where we finally clarified. There was a lot of talk about potentially being an upstream inhibitor. You might trigger autoimmune activation or SLE. We finally had agreement with the FDA. The FDA agreed with us. Yeah, no, that doesn't make any sense. And testing for ANAs, like we did in the Phase II study, is no longer required. That's irrelevant, and it's not telling you anything. In our Phase II MG trial, the number one reason for screen failures, 40% of patients failed our screening criteria because they had high ANAs. That's despite having no history of lupus, no family history of lupus, no symptoms of lupus. It just turns out that MG patients, like many autoimmune patients, and even healthy people, Have high ANAs for no reason. So, we've eliminated that. We agree with the FDA that that was a waste of time and not needed anymore. So, we don't screen for that. So, that may help us with recruitment. Can you talk about the QMG screening criteria as well? Right. So, if you look at our Phase II data, this was a small proof-of-concept study. We had about 20 to 21 patients per arm, and yet we had statistically significant efficacy within seven days. Every single week we have statistical significance. And that's despite the fact that the placebo arm had a higher response rate than any other complement study seen before that. Typically, responders in placebo have about a two-point improvement on MG-ADL. In our study, it was 2.8, almost three. So when we look at the data, we ask ourselves, why is that? Well, we only had the MG-ADL as a screening criteria. The MG-ADL is a really simple, look it up, it's a really simple self-administered scale by patients. It literally takes five minutes. It's eight questions. Typically, studies also have a QMG screening criteria. QMG is a much more involved physician-administered scale where it could take up to two hours. We were a young company, new, first time into the MG space. We thought if we have MG as a screening criteria, we are going to, you know, we're just gonna set up a hurdle and may slow down recruitment. Let's just take out the QMG screening criteria. We don't need it. What you see in our baseline characteristics is on the MGDL, These patients seem to be moderate to severe. But when you look at the QMG, they're not as moderate to severe. And so we did a sub, sorry, post hoc analysis, and all the caveats around post hoc analysis. But we did a post hoc analysis, and we said, well, what if we had had a QMG scale screening criteria of at least a score of 10? We don't lose that many patients when we do that, and all of a sudden, the placebo's closer to two-point improvement, and our difference from placebo is a three-point improvement. No biologic has ever hit three on the MGA-DL versus placebo. That's partly why we have confidence that potentially we might have better MGA-DL scores than C5 inhibitors, and maybe the best in disease profile, and it's because of that upstream inhibition. We prevent C3A, we prevent C3B, and that, we believe, will add to the efficacy on top of eliminating the MAC formation. So, we have the QMG screen criteria now in our phase three. We've learned other lessons about what kind of patients were placebo and had high response. So, we're implementing all those lessons, and our hope, of course, is that at the end of the day, the phase three trial, that the placebo patients will be closer to a two-point improvement, as we've seen historically with other complement inhibitors, and then we can see what clasipobar can really do.

Alex Thompson, Analyst — Stiefel

So then maybe I wanted to sort of talk about the pipeline beyond Classiper BART and sort of maybe at a high level how you're thinking about You know, taking on more biologic risk here with 2-1-2 and 3-1-2.

Marino Garcia, CEO

I'm sorry.

Alex Thompson, Analyst — Stiefel

Sorry, yeah, so let's talk about the pipeline with 2-1-2 first and then 3-1-2 and how you're seeing the progression of that beyond CaciproBart.

Marino Garcia, CEO

Yeah, so look, from the very beginning, we've been on a mission to build a really exciting biotech company, and that requires a pipeline. And I think, you know. Lessons I've seen from other companies that have been very successful, but mostly single-product companies, if they had a regret, it would be that they didn't put enough energy and time into building a pipeline earlier on. So our focus is on other antibodies that have a potential best-in-class profile, not just a convenience plate, for example, but potentially better efficacy or safety and or convenience. So our second program, 212, in license from Leeds Biolabs. In China, it's a bifunctional fusion protein targeting BDCA2 and BAFAPRIL. On the BDCA2 side, it depletes PDCs, and it looks like it's more potent than Lidofilmab from Biogen, who will have two SLE phase three studies reading out in the first half of December. And then on the other side, BAFAPRIL. That looks like povitacicep in terms of IG reductions, but with a longer half-life. And so the idea here is to take it into conditions like SLE, Sjogren's, dermatomyositis, areas where we know both mechanisms have evidence that they could work. And the idea here is to shut down the innate and adaptive immune system to help bring about better efficacy, more robust efficacy, broader symptoms, more patients responding. When we brought this product profile to our KOLs in the SLE space, they said, guys, this is exactly what we need. You know, I'm not going to be able to prescribe, you know, Benlista and Lofilumab to one patient. If you can combine whatever these mechanisms can do into one and address more symptoms and even get more patients to respond, better efficacy, more robust response, that's ideal. So that's the mission we're on with 2-1-2, and right now we're in phase one.

Alex Thompson, Analyst — Stiefel

Yeah, so maybe for 2-1-2, I guess I like the idea of innate plus adaptive immune suppression. I guess both of those pathways come with their own particular safety questions, and what gives you confidence that you can kind of actually achieve that clinical advocacy with a therapeutic index that's reasonable?

Marino Garcia, CEO

Well, we're early on in phase one. That's what we're trying to do. We know at a very low dose, we maximize the potency in terms of the PDCA2 side, the PDC depletion. What we're trying to figure out now is what's the optimal dose for the Baph-April side to make sure that we get IgE reductions that are at least similar to, for example, Povitacep, which we think is the best-in-class Baph-April. And, of course, with that, are there any new safety or tolerability signals? And then that's what we'll take forward into a MAD study, which we plan to initiate in the second half of next year. We're already testing 212 NSLE patients in China, so we'll have data in disease patients, not just in healthy volunteers next year. And I have very high hopes for this. This drug, assuming all goes well in a few years, could be even bigger than Closyprobar is for us.

Alex Thompson, Analyst — Stiefel

So what do you want to see out of these Phase I data in the first quarter?

Marino Garcia, CEO

Just understand what dose has that proper sort of risk-benefit profile, where we can maximize the BDCA2. BDCA2, like I said, we get that at very, very low doses, but where's the dose that we get the ideal best-in-class or equal or better than Povetacacept on the Baph-April side? Yep.

Alex Thompson, Analyst — Stiefel

And then would you move right into sort of a U.S. study, or how are you thinking about progressing into the lead indication of Sjogren's SLE and DM?

Marino Garcia, CEO

We'll talk more about that. The team's working very hard on how we can get creative and create as many calluses and move as fast as possible. Maybe it's a combination of phase two, three, adaptive type of designs. So we'll have more on that next year. The key here now is to finish our studies in China, which is the SLE and the SAD portion of the phase one, and then for us to take over and start executing on the MAD study outside of China. Okay.

Alex Thompson, Analyst — Stiefel

So then where does 312 fit into the story?

Marino Garcia, CEO

312, I'm really excited about. This one was created by our small but mighty team. We literally only have four research people, and they created this bifunctional fusion protein. Essentially, the idea here is take clasipibart, the upstream inhibitor within the complement system that's highly potent with a nice long half-life, and attach to it a best-in-class bath aprile that goes even further upstream and fleets B cells, put it together into one therapeutic, and go after MG, CIP, and MMM, again, for potentially more robust efficacy, more patients responding, expand beyond ACHR-positive patients in MG, for example. And it looks really great. It's exactly like Clacipibart, pre-clinically. And on the other side, we look like we have POVY-like reduction IGE levels, but with a longer half-life. And we'll be ready at the end of phase one. We'll be ready, sorry, to go into phase one by the end of next year. But from a CO perspective, think about that. You have a team that you've built all this expertise around Clacipibart, MG, CIDP, MMN. And just as they're finished, those three indications, and developing them, and hand it over to the marketing folks to launch and create the blockbuster we know it can be. What do you do? Well, typically in a biotech company, you start losing those people unless you have something. At that moment, we give them 3-1-2, and we say all the expertise you've built up, all the lessons learned, all from mistakes we've made, because we have made mistakes. Everything we have in terms of built up in equity, now go and execute on a next generation, even better approach, potentially, for MG, CIP, and MMM. That's very exciting. We have all the relationships, all the investigator sites. It's a really nice way to, at some point, then come out and say, hey, you love BAF April? Potentially, if they're approved in MG, for example. And you love Classypibart? Look this. Now we have the next generation therapeutic.

Alex Thompson, Analyst — Stiefel

And how are you thinking about, you know, obviously the C1S mechanism could go beyond MGCIDP and MMMN. How are you thinking about... Going beyond those three indications between ClasipaBard and 312.

Marino Garcia, CEO

Yeah, ClasipaBard will definitely be able to go into more indications just because of the dual mechanism, obviously. But with ClasipaBard, look, that's our baby. That's the foundation of the company. And I'm not comfortable taking it into any conditions unless I have two big check marks on two criteria. One, are we confident it's going to work? There's probably a success very high in the clinic. And then secondly, is the market opportunity exciting? Like, we could take this into hematological indications like coldagglutinin disease ITP. We know it will work, but I can't get excited about the commercial opportunity there. Now, the myositis conditions, that could be interesting. TrueGuy has a sweeping C1S inhibitor they're testing, and they were supposed to, they're doing a basket study of myositis conditions. They were supposed to have results this year, but they moved it into the first half of 27. I'm eager to see that. If they show a nice signal on efficacy in myositis conditions, including dermatomyositis, that might be the green light to go ahead and test classibabar and some other indications. But I really need those two criteria to be very high scores before I do anything with classibabar. 212 and 312, I'm more willing to take risks. We're a different company. They're not the foundation of Dianthus.

Alex Thompson, Analyst — Stiefel

Yep. Yep. So maybe the last question, sort of, can you talk about where you're at with Cash Runway and what's embedded in those assumptions?

Marino Garcia, CEO

Yeah, we have $1.2 billion cash. We're very fortunate. That takes us into 2030 and allows us to read pretty much every major catalyst between now and then and start to build out the commercial organization for launching Klasipibart. So in a very, very strong position. Awesome. Marina, always a pleasure. Thank you. Thank you, Alex, again.