Dianthus Therapeutics, Inc. (DNTH) Earnings Call Transcript & Summary

Good afternoon. I'm Sam Semenkow, one of the senior biotech analysts here at Citi. And it is my pleasure to be hosting Dianthus at Citi's 2026 Biopharma Back-to-School Sumit. I'm joined by Marina Garcia, CEO of Dianthus. Marino, welcome, and thank you so much for being here.

Thank you, Sam, and thank you to Citi for allowing us to be here today and for hosting this webinar.

Absolutely. So why don't we just start maybe a little bit high level. You made a ton of progress across your pipeline this year. So lots of great updates that have come from you guys. And there's still a few catalysts outstanding before the end of the year. Could you just maybe recap and level set where the company stands today and what can we can expect you through the end of the year and maybe over the next 6-ish months.

Sure. So thank you for that. And again, thanks for the opportunity to update everyone today. So over the last 12 months, with Claseprubart, we have had 2 big moments in our development of Claseprubart neuromuscular conditions. We had the very positive Phase II MAGIC results and myasthenia gravis from September or exactly about a year ago this week. And then the CIDP update, the early interim responder analysis we announced in March and then the fulsome update on our first 40 patients as part of the interim responder analysis in June. From our perspective, Claseprubart is now pretty much derisked as a very prone neuromuscular therapy and antibody. So the next update is on the third indication. It's our Phase II results with MMN, which we are expecting to announce our top line results in December of this year. That is a Phase II study. Originally, it was slate of 12 patients per arm. We've overenrolled, which is great. It shows a lot of enthusiasm for the program in the MMN community. So we'll have about 15 patients per arm. So relatively small Phase II, mostly a safety study. That's the primary endpoint. Secondary endpoints are efficacy measures and mostly exploratory. So the expectation there is, again, we'll report out if we see anything new on safety. And I can tell you on a blinded basis to date, it looks very similar time to CIDP. So no new surprises. And of course, we're looking for just numerical trends. We're just looking for the numbers on the efficacy measure, the second area end points to be moving in the right direction. And really, our goal is to get to a Phase III start as fast as possible. Back in 2024, when we met with the FDA to discuss the MMN program, we would have liked to have been able to go straight into a Phase III the way we did with CIDP because it is an SBLA. But at that point, the FDA really did not know what our Phase III should look like. They didn't have direction to give us in terms of what the primary end point should be. So it makes sense to do a Phase II. But obviously, like CIDP would have loved to have had a precedent and being able to go straight into Phase III. So we'll move to as quickly as possible into Phase III with MMN. And in terms of 212, our next program, our bifunctional fusion protein, that is in a Phase I study in healthy volunteers. We'll provide an update on that by the end of the year and provide some visibility on when we'll start the MAD portion of the Phase I and what our plans are over the next 12 months. We'll do that by the end of this year. And then recently, we announced 312 that we are moving that into getting Phase I ready by the end of next year. Those are some of the big moments. On Claseprubart, we will provide another update on CIDP. That will be before the end of the year, just provide guidance on when to expect top line results for the Phase III captivate study. also provide an update on what we truly think the end will look like in Part A. Remember, we're -- the goal of the study is to recruit 128 patients into Part B. And those are patients who will have responded on Part A. Right now, we're saying we need up to 256 patients in Part A to get to that 128 in Part B. But if our responder rates look consistent with what we updated earlier this year, and to date, they do look consistent, they're staying fairly consistent. If those responder rates continue to remain consistent throughout the end of the year, then we won't need anywhere close to 200 patients even in Part A. So I'll provide a bit of an update on that, and that should be an important catalyst. And on MG, we've just initiated the EMERGE study, where we're studying 2 different doses, once every 2 weeks or once 34 weeks. And we're screening patients, and that's all on track, and we expect results from MG top line results from that Phase III study in the second half of 2028.

Thank you for that. a lot to dive into. I think I'm going to choose to start in MG because that's where you ended. So I mean, the Phase II data that you presented is competitive. You've [indiscernible] being your dosing presentation and regimen, it's, I think, easy to see how you were a best-in-class complement inhibitor, but also more broadly, just across the GMG landscape, where do you see it fitting in? Like what's the offense of the market does Claseprubart have the opportunity to take meaningful share?

Yes. And I'll just add one element that you didn't mention in the market research we're doing with neurologists, one thing that came back very early on with some of the first neurologists we spoke to when we presented data to him is, you guys should emphasize how fast this I mean the stats separation on QMG and MG-ADL within 7 days is also really impressive and important for MG patients and neurologist and a key differentiator. So in terms of where we expect, I mean, if you can imagine the MG landscape when Claseprubart is available, you'll have FcRns and different versions of FcRns available. You'll have UPLIZNA, maybe you'll have BAFF/APRIL, we'll see what the data looks like from [indiscernible] and Vertex, et cetera. And then you'll have the complement class, which has been the case -- it's a foundational class in MG has been there forever, and it's still being used first line. Obviously, [indiscernible] has done a really good job of getting first-line use, and C5 are being moved more and more to second line. But within the complement class, you'll have all sorts of different C5 inhibitors and only 1 C1 inhibitor, only on pure classical pathway inhibitor that won't have any box warning a REMS program, and that will be potentially a once-a-month subcu auto-injector like Dupixent. If you can imagine a label for a product like Claseprubart, where you just take the safety and tolerability from Enjaymo or sutimlimab, which is approved in the U.S. for cold agglutinin disease, just cut and paste that safety label, put it on ours and then go to the dosing administration for DUPIXENT, but make it once a month, the exact same injector. That's what you're going to be launching with, put that into our label. And an efficacy that's at least as good as C5s, potentially better and works within the first week. Literally, after your first dose, you see efficacy, you should respond if you do respond. I think if we price that intelligently and competitively, I should get a pretty nice share of first-line use. And then in terms of second line, I mean if someone started on FcRn, the database -- the claims database, if you look at it in the U.S. right now, at least 40% of patients are not on therapy 12 months later. Clearly, FcRns don't work for everybody. Clearly, some patients are not going to be tolerating it or not enjoying the dosing administration challenges with a high-volume therapy. I think the next logical step would be something like Claseprubart. And so I see it as being a major blockbuster getting a fair share of first-line use, certainly getting a good chunk of second-line use. And that easily with a large market like in the United States where less than 20% of patients right now are on biologics. If you think about a healthier, younger more active patient with a busy lifestyle traveling who wants something super easy. They can just travel with it, keep it at room temperature and their bang and, dose it to them, give it to themselves wherever they are around the world when it's time to take their shot. I think Claseprubart will be a very, very successful product in MG.

And you've talked about this with me, and I have my own survey data to back this up that neurologists do want to use new therapies that get approved here and sometimes as first-line therapy is ahead of FcRn and sometimes after FcRns. It's a bit of a mix. But do you see Claseprubart fitting into that as well? And maybe you could talk to some of your market research that you do?

Yes. I mean our market research shows that if you have something where you can say, look, it's an auto-injector, you keep in the fridge. And if you need to travel and you're not going to be home when your next dose is up in the next month, take it out, probably be able to keep it at room temperature up to 4 weeks. You can literally give it to yourself anywhere. It's an non-injector -- go to the DUPIXENT website, watch the patient video. It is amazing how easy it is. You don't see the needle. It's a 27-gauge needle. It will be very easy to self-administer, literally takes 5 to 7 seconds for the dose to be given and you're done. And we will have the stability data to show that you can keep it a room temperature up to 4 weeks outside of the fridge and travel with it. So physicians tell us that if you have something like that, no box warning, no REMS program works really fast, potentially better efficiency. There is a potential here for an upstream inhibitor to show if we can control placebo response well in our Phase III, and we think we know how to do that and keep it to a 2-point improvement on the MG-ADL for the placebo arm. There's a potential here, we could show better efficacy because it is an upstream inhibitor versus C5. I mean something like that, even if it is similar C5 efficacy, just a safety advantage, the dosing administration, look at UPLIZNA. I mean, honestly, it's a bit of a dirty drug, CD19. It's not perfect. It takes quite a while, once to see the efficacy you can, but it's doing so well. Why? Because it's a new option. And the only advantage it has is that is an IV every 6 months. This market is hungry. It should be 40% to 50% penetration of biologics. It's not because there's no therapy that's ideal yet. And I think Claseprubart gets very close to the ideal to really push that penetration of biologics in the MG market.

And you didn't mention this yet, but you have a Q4 weekly dosing regimen included in the Phase III, which could really even extend that dosing just quarterly, which to your point about UPLIZNA has advantages.

Right. No. So our dosing regimen in the Phase III is once every 2 weeks and once every 4 weeks. It will be once every 2 weeks in CIDP and MMN. But in MG, I think it will be every 4 weeks. I don't think we'll see a difference in efficacy between those 2. And the reason is there's more and more evidence showing that you do not have to shut down the classical pathway the way every 2-week dosing does that getting somewhere above 70%, 75% inhibition of the classical pathway is enough to maximize efficacy in MG. So if that's the case, we have a 1 to month drug. There's no question. And that data comes from cemdisiran data, where they show 25% inhibition, got them a fairly good improvement on the MG-ADL versus placebo. We have our own data from our open-label extension that shows that PK levels that are half of what are dosing every 2 weeks would achieve. Still, you have patients responding on the drug significantly. So really, it doesn't look like you need to get above 90% on MG -- in MG patients in terms of inhibiting the classical pathway to maximize efficacy. So we'll see, but we're still testing every 2 weeks. Either way, honestly, this is -- in terms of dosing administration, the feedback from neurologists and patients says, this is a winner. It's infrequent. It's easy, no box warning, no rams program, either way is a win. But of course, if we can do it once a month, and stay 2 weeks, why not.

Sure, for sure. And then maybe if we switch gears to CIDP from a commercial standpoint, I'd argue that there's even more white space in CIDP. Maybe it's a little bit easier to penetrate the market for a new therapy to take share. But the market is smaller. So I'm wondering just how we think about cost of refit into that treatment landscape since there are other complement inhibitors that are in development from Argenx and Sanofi.

Sure. SP-8 Well, so Sam, if it's okay, I might challenge a little bit on something you said, which is that maybe CIDP, there's more white space. If you look at the CIDP market, historically, IVIG is really well entrenched. And if you've listened to Argenx over the years, they've tried to really moderate expectations because IVIG is so well entrenched and it works in CIDP. I think the issue is if you have a treatment that is even more efficacious than IVIg, that are tolerated, no box warning, and self-administration subcu, like we are going, then yes. Then this market will be wide open for a therapy like that. FcRns are not as effective as IVIG. They're better tolerated. They're more patient-friendly. So definitely a nice innovation for the space. But in terms of efficacy, there's nothing that comes close to IVIG right now in the market. Our data suggests that inhibiting the classical pathway in a very potent way like we do with Claseprubart may improve how patients are responding to standard care, including IVIg even further. That's what we're seeing in our Part A open label. Because of that, the biggest opportunity in CIDP is converting patients from IVIg is having them switch. And right now, if they switch FcRn, I mean there's a risk of -- a significant risk of relapse. What we're seeing in our party, which is an immediate switch from standard care, including IVIG, 3/4 of patients are doing even better on Claseprubart than they were doing on IVIG. That was information we didn't know before this year. That's clearly what we're seeing in Part A of our CAPTIVATE trial. In terms of what that means? Well, CIDP -- the value of CIDP for us is definitely increasing because of that. And then on top of that, when you look at what our competition for classical pathway inhibition is, well, first with riliprubart, they now have terminated mobilize for futility. So they'll have 1 negative placebo-controlled trial and now vitalized, which I suppose it was a positive futility analysis, so that's moving forward. So as far as I can tell, they'll have 1 negative placebo-controlled trial, 1 positive placebo-controlled trial possibly. I'm not sure if you can file a BLA with that. I'm not sure what they're going to do. If they believe like I do, that you need a second placebo positive control trial that -- to file our first BLA that means they have to start another trial, and that would definitely delay their introduction to the market and they would come off to us. So there's a strong chance here that riliprubart doesn't even make it to market. But if they do, that's fine. They are 4x more injections than us. And let's assume everything else is equal, although we'll probably have good data in refractory patients, and they won't have that because of ending the Mobilize trial. And then there's empasiprubart. We'll get further updates, I'm assuming on their progress later this year, but empasiprubart is of the 3 -- riliprubart, UZ and empasiprubart. Of the 3, it is the weakest of the classical pathway inhibitors. Does that matter? I'm not sure. But I know for sure, they block the lectin pathway as well as the classical pathway. That means they're going to have a box warning. There's no other way for your complement system to respond to the presence of encapsulate bacteria. If you block both lectin, I'll turn and sorry, in your Cosco, there's no way for them to initiate the cascade, trigger the alternative pathway to rev up and create more MAC to go and like the bacterial infection. So they'll have a box warning and they're an IV. So in the end, if they do get approved for CIDP, there'll be another option, obviously, but that one will have a safety disadvantage and certainly a dosing administration disadvantage. And that's assuming efficacy is equal. But again, a potency matters in CIDP, we should have better efficacy as well. So that's it. And there's really nothing else right now that I see coming into the CIDP market. So for us, we're very, very focused on getting to the best level possible there, of course, in a positive outcome with CAPTIVATE, our Phase III trial. And then the strategy will be very focused on going after the IVIG patient population. If you talk to patients who have CIP and IVIG who are stable and doing well, they'll tell you they thank God for CIDP -- sorry, for CIP, I apologize for IVIG, it saved their life. But boy, would they love to be able to get on something else. And even if it's just similar on efficacy, if you come to the market with something that looks like it might be even better and better tolerate no box warning and self-administration, sub-2 self administration, that's a game changer. And one last point. The largest patient population we are recruiting into CAPTIVATE are patients who are stable on standard care, including IVIg. Think about that. These are patients who are supposed doing fine, and they're on IVIg. Why would they risk going into a trial and changing their therapy is because they're looking for something that's equal or better on efficacy, but just much better tolerability and much easier to take. And that is really the huge unmet need in CIDP.

When you talk to physicians, sometimes though, to your point, IVIG is very entrenched I guess what do you think physicians want to see in order to change that treatment paradigm? And also particularly, IVIG is still used as a diagnostic for CIDP. I mean, is there a first-line opportunity down the road once you have patient physicians have more experience or -- and just in the beginning that you're really focused on that switching market?

Yes. I mean when I say switching focus, I'm just saying that's the largest opportunity because there's a huge amount of patients who have been diagnosed and on IVIG. Of course, positioning it as a good first-line therapy will be the ideal position to take. I mean in naive patients in our trial, we're seeing near 100% response rates in the early patients that we've seen in Part A. Look, when we have the results from CAPTIVATE, I think what physicians are going to be very interested in seeing is what happened when you just switch patients within 7 days, there's no wash out, there's no making patients relapse like you saw in ADHERE trial and CAPTIVATE, we literally take a patient who is on standard care or IVIg within 7 days, just switch them. What happens? And if you see very little relapse rates, if you see maybe another chunk of patients who stay stable, but they're now on a much better tolerated, easier to take drug. But if you're seeing like what we saw in our first 40 patients close to 3/4 of patients doing better, improving. I mean that's how we would define a responder in Part A. These are patients who are being switched immediately and doing better. I mean -- and if you look at our slide deck in our corporate deck, it's not just 1 point improvement on the cat. I mean it's every measure, consistent across very robust response rates. Physicians are going to be very comforted by that. And then on top of that, again, you are able to not have a box warning, no REMS program, and it's an auto-injector that a patient can give themselves anywhere they are around the world. every 2 weeks, like a DUPIXENT. I mean I think that's as long as we don't do anything great on pricing. And if we are going to be more expensive than IVIG. So do I expect some payers to maybe say you have to try IVIG first? Sure. But can you imagine what -- you know what neurologists patients are going to do, okay? We're going to try IVIG, payers tell us we have to do this. If you can't tolerate it, though, then we can try something else. I mean no patient is going to come back and say, I love this. this is great. I tolerate really well. I'd love the dosing administration. That's not going to happen with IVIG. So there's just a huge opportunity. So for us, CDIP, I mean I think it's very fair to say it's become an even bigger opportunity now than MG was. And MG was always a huge blockbuster opportunity for us.