Dianthus Therapeutics Aktie

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 Summit. 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 to 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 in neuromuscular conditions. We had the very positive Phase II MAGIC results in 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 potent 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 slated to have 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 to MG, very similar 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 secondary efficacy endpoints 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 a Phase III should look like. They didn't have any direction to give us in terms of what the primary endpoint should be. So it made sense to do a Phase II. But obviously, like CIDP, we would have loved to have had a precedent and be 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 get it 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. We'll 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 every 4 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. We have 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 have clean safety, convenient dosing presentation and regimen. It's, I think, easy to see how you are a best-in-class complement inhibitor. But also more broadly, just across the gMG landscape, where do you see it fitting in? Like what segments 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 them is you guys should emphasize how fast this works. I mean the static separation on QMG and MG-ADL within 7 days is also really impressive and important for MG patients and neurologists 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 and maybe you'll have BAFF/APRIL. We'll see what the data looks like from Vor and Vertex, et cetera. And then you'll have the complement class, which has been a class -- it's a foundational class in MG. It's has been there forever, and it's still being used first line.

Obviously, efgartigimod has done a really good job of getting first-line use. And C5s 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 one C1s inhibitor, only one pure classical pathway inhibitor that won't have any box warning or 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 auto-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, that should get a pretty nice share of first-line use. And then in terms of second line, I mean if someone started on an 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 MG in the United States, where less than 20% of patients right now are in the 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 in their bag and dose it to -- 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 therapies ahead of FcRns, sometimes after FcRns. It's a bit of a mix. But I do 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 it 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 auto-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 at 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 than C5. 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, months to see the efficacy kick in, but it's doing so well. Why? Because it's a new option. And the only advantage it has is that it's 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 to just quarterly, which to your point about UPLIZNA has advantages.

Right. No. So our dosing regimen in our 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 once-a-month drug. There's no question. And that data comes from Cemdisiran's data, where they showed 75% 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 our 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 REMS program. Either way, it wins. But of course, if we can do it once a month instead of every 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 Claseprubart fit into that treatment landscape since there are other complement inhibitors that are in development from argenx and Sanofi.

Sure. 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, better tolerated, no box warning and self-administration of 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 of 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. It is having them switch.

And right now, if they switch to FcRn, I mean there's a risk of -- a significant risk of relapse. What we're seeing in our Part A, which is an immediate switch from standard of 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 one negative placebo-controlled trial, and now they have VITALIZE, which I suppose there was a positive futility analysis. So that's moving forward. So as far as I can tell, they'll have one negative placebo-controlled trial, one 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 uour first BLA, that may mean they have to start another trial, and that would definitely delay their introduction to the market and they would come after 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, [ us, ] 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 encapsulated bacteria. If you block both lectin alternative and -- sorry, in your classical pathway, there's no way for them to initiate the cascade, trigger the alternative pathway to rev up and create more MAC to go and lice 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, if potency matters in CIDP, we should have better efficacy as well. So that's it. 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 label possible there, of course, and 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 do -- might be even better and better tolerate no box warning and self-administration, subcu 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 of care, including IVIg. Think about that. These are patients who are supposedly 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 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 washout. There's no making patients relapse like you saw in ADHERE trial. In CAPTIVATE, we literally take a patient who is on standard of 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 and our corporate deck, it's not just 1 point improvement on the [indiscernible]. 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 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 crazy 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 -- do you know what neurologists and 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 love the dosing administration.

That's not going to happen with IVIg. So there's just a huge opportunity. So for us, CIDP, 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.

In my defense, that's what I meant by more white space.

I mean it's -- if you can show that you are switching patients off of standard of care and they're getting better in a very robust manner very quickly, I think that's a game changer in CIDP.

For sure. And so we look forward to that update that you're going to share at the end of the year sort of for a timing. Yes. Well, I'll try to be patient. I do want to spend a little bit of time on MMN since it is your next data catalyst. You gave us a little bit of a preview on what to expect there. It's a safety trial. You're looking for trends. But is there a threshold? If everything moves in the same direction, is that enough to convince you to move to Phase III? And maybe complicating or hoping we'll see, you're also getting argenx's MMN data around the same time. So how should we in the investment community really think about positioning as we move into that? How should we like frame our expectations, I think is a better way to say it.

Sure. Look, I don't want to sound overly confident or flipping here. There's almost nothing that we can see in Phase II that will convince us not to go into Phase III. We know MMN is IgM driven. That's triggering the classical pathway. We know MMN is a classical pathway-driven disease. We know dosing every 3 -- every 2 weeks with 300 milligrams. We are getting very potent inhibition of the classical pathway. There's almost nothing that we're going to see that's going to prevent us from going into Phase III.

Literally, again, Phase II was -- this Phase II trial was a safety study primarily. We're not seeing anything new, no surprise. We expect to see some numerical changes on the secondary endpoints, the efficacy endpoints. None of them -- we don't expect any stat sig. The numbers are too small. Just like with empa, their study was a little bit larger actually, they're Phase II with empasiprubart, and they didn't see any stat sig. That's it. We're just going to move to Phase III as fast as possible.

The key is what can we learn from argenx's Phase III. My hope is that they show non-inferiority to IVIg and that their study was a success and that the primary endpoint should be grip strength. And so then we will just replicate what they've done, go to the FDA, get agreement and start the study as fast as possible. If they show noninferiority but not superiority, that leaves the door open. If an MMN, you can get better efficacy by being a more potent classical pathway inhibitor, then it leaves the door open for us to potentially show superiority.

If they show superiority versus IVIg, that's fantastic. That shows that even not being a very potent classical pathway inhibitor is enough to show that you're better than IVIg and MMN. And IVIg is not greater than MMN, but it is approved. So that would be a really great development for patients and certainly should give investors comfort that we will show the same because we are a more potent classical pathway inhibitor. Now there is a scenario where somehow they don't show that they're even non-inferior if they have a failed study.

If that's the case, I would just remind investors, we had the same situation with riliprubart and Sanofi in June with MOBILIZE. And after a couple of days of intensive discussions with investors, I think people were reassured that they have to remember, we have a very potent classical pathway inhibitor, more potent than riliprubart and even more potent than empasiprubart. We're 7x more potent than riliprubart at the [ I.C.9.e ] on the CH50 [indiscernible] assay. We are 38x more potent than empasiprubart in a head-to-head comparison we have in our slide deck using the same assay that argenx used to demonstrate their potency in their publication.

So if they somehow just did not shut down the classical pathway enough, I remind people, 300 milligrams every 2 weeks, we get over 90% inhibition. That is really shutting down the classical pathway. We will see efficacy. So I just -- I can't really imagine right now why we would not go into Phase III, even if empasiprubart's study is a fail because we do have a different classical pathway inhibitor, a much more potent classical pathway inhibitor. So I hope they're successful. That will be reassuring for everybody. Patients will benefit from that, and then we can come in with a, I think, a better profile once we get approved -- assuming we get approved, of course.

Looking forward to seeing the data from your trial as well as argenx is done. Something to look forward to. So I do want to leave a little bit of time to talk about your early-stage pipeline, 212 and 312. They're both very interesting assets. And for 212, you've prioritized SLE Sjögren's and dermatomyositis. Once we get the data later this year for the healthy volunteer study, how should we think about how you're going to prioritize and go about the path of developing 212?

Right. So to be clear, what we're going to provide by the end of this year is just an update on how the SAD portion, the single-dose portion of our healthy volunteer Phase I study is going and then provide visibility into 2027, when are we going to start the MAD portion and then our thinking around the 3 indications and when those studies will start. So that's going to be the update later this year.

I still believe and we still are planning for SLE to be the first indication we go after because that's where the highest probability of success is. And we'll have another derisking moment from our competitors will be Biogen's Phase III data in SLE with Litifilimab, which is their BDCA2 therapy. And we look like we are more potent in terms of pDC depletion. We're hoping they'll have stat sig and be a positive outcome and show separation from placebo. And then again, that should reassure folks that 212 should have at least similar efficacy probably better because it has the BAFF/APRIL side.

So later this -- yes, later this year, we'll provide an update on how the single dose portion of the Phase I healthy volunteer study in China is going and provide more of an update on when we'll start the MAD studies and when to expect or the MAD cohorts, I should say, and then when to expect data from that as well.

And the MAD cohorts are going to be also in healthy volunteers or as...

Yes. And if we are looking to do any part of the Phase I in patients, we'll also provide an update on that.

Got it. Understood. And then you also mentioned you recently unveiled 312, which is, I guess, next-generation Claseprubart, if I may, the C1s and the BAFF/APRIL dual inhibitor. Very interesting like life cycle management for Claseprubart also allows you to expand beyond Claseprubart. Can you just talk about your vision for how you're thinking about developing this molecule as well?

Yes. I mean I'm really excited about that one because obviously, it builds on our experience now we have with Claseprubart. We know Claseprubart inside out. And the idea here is, if you can imagine, by the time our clinical development, clinical operations, regulatory, everybody is done with developing Claseprubart and handing it off to the commercial organization to go launch, we have all this expertise, all these relationships, all these insights we've learned from developing Claseprubart in MG, CIDP and MMN. And all of a sudden, we give that same organization 312, which is essentially a more powerful version, a more -- potentially more effective version than Claseprubart or any BAFF/APRIL and certainly the 3 neuromuscular conditions.

So the idea here is to take all that expertise, all those lessons learned, all those relationships, KOLs, investigators, all that knowledge and then apply it and move as quickly as possible with 312. And then there's definitely more indications we can go into with 312 because of the BAFF/APRIL side as well as the active C1s inhibition side. And those indications will determine at some point in the near future, but definitely starting with CIDP, MMN and like I said, MG. It has a longer patent life. And you can just imagine the kind of franchise we could build in the neuromuscular field and that expertise that we're building with Claseprubart and then we'll have built with commercial by the time 312 also launches. It's really exciting.

And with the extended IP and the extensions we'll probably get to that IP, I mean, we could be in this neuromuscular field into the 2050s with this franchise. It's really, really exciting.

Yes. Looking forward to seeing that one progress over time. So we are at time, but I wanted to give you maybe an opportunity to share any closing remarks that you had, maybe recap the runway -- cash runway for us. And I think you've done a great job at outlining the catalysts, but if you want to emphasize that as well.

Sure. So look, for Claseprubart, it's our Phase II MMN data in December as well as our argenx's Phase III MMN data with empasiprubart in the fourth quarter. With 212, it's our healthy volunteer update and Biogen's Litifilimab update on their SLE Phase III study with our BDCA2. On CIDP, I think that will be an important catalyst. We'll provide an update on Claseprubart and when to expect that Phase III study to read out and how we're seeing the end that we need in Part A in order to get to 128 patients in Part B, how we see that evolving.

And like I said, if the current trends continue, then we are not even going to need 200 patients in Part A to get to that 128 patients in Part B. We have $1.2 billion in the bank that takes us into 2030. So we have plenty of cash to execute on all 3 programs in all the different indications and read out all the important catalysts in the next few years. That gives us just a lot of optionality. And the team is doing a great job, and we're feeling -- I'm feeling really, really pumped, really excited. And I can't wait. I could see 212 and 312 adding even more value to the company and for shareholders over the next few years than Claseprubart has to date. So I feel like we're just getting started.

Yes. Lots to look forward to. Well, thank you so much for the time. This has been wonderful, and I really appreciate you being here, Marino.

Thank you, Sam. I really appreciate it.

Great. Hi, everyone. I'm Matt Vandenbosch. I'm on the health care investment banking team at Goldman Sachs. I'm joined here today by Marino Garcia, the CEO of Dianthus Therapeutics. Marino, thank you for making the time.

Well, thank you for the opportunity to update everyone on what's going on at Dianthus. I appreciate it.

Excellent. So I guess for those a little less familiar, can you just provide a brief background on Dianthus.

Sure. So Dianthus Therapeutics, we are building a really exciting autoimmune company focused on rare diseases. Our first program is a very potent classical pathway inhibitor, an active C1s inhibitor called Claseprubart, where we are taking it into building a nice sort of neurology neuromuscular franchise with it. We've already had two very strong catalysts or proof-of-concept moments in myasthenia gravis, the first indication with our Phase II data back in September of last year, where we raised $288 million. And then earlier this year with an interim responder analysis, it was actually in an early [indiscernible] CIDP, the second indication [indiscernible], where we raised $719 million on that announcement.

So we have $1.2 billion in cash, which will take us as a runway into 2030. It will allow us to read out multiple catalysts for Claseprubart, including the Phase III for our MG trial, which we're starting imminently. And we'll provide further guidance on when we expect the Phase III results in CIDP.

And in terms of -- and the third indication we're going after with Claseprubart is MMN, multifocal motor neuropathy. And for that, we have our Phase II results, which we'll read out in the fourth quarter of this year. And we're on track, and everything there from a blinded perspective is looking really good in terms of the safety and tolerability, very consistent with everything we've seen in the two other indications with Claseprubart.

And the whole idea here is with this pipeline of product, Claseprubart is that we are going to deliver really great efficacy in the three neuromuscular conditions. And as a comp inhibitor, do it in a safer manner, where we can avoid a box warning for the risk of infections from meningococcal infection from encapsulated bacteria like meningitis. And do it with an auto-injector, a 2-milliliter auto-injector, actually the exact same one DUPIXENT uses, where patients could self-administer it every 2 or 4 weeks. So in a very convenient form for patients to be able to live their lives independently of infusions or having to go through very long sort of self-administered subcutaneous injections like, for example, with efgartigimod. So that's our first program.

Our second program, we licensed in from Leads Biolabs in China. It's a bifunctional fusion protein. Again, pipeline of product potential, potential best-in-class or best-in-disease potential there. And that is targeting both BDCA2 or looking to reduce type 1 interferon on one side and on the other, BAFF/APRIL. And the idea here is to bring about two mechanisms that we know work in certain conditions, like the first three indications we've announced, like SLE, Sjögren's and Dermatomyositis, where there's very strong evidence for both mechanisms, put that into one therapeutic, and hopefully, to bring about better efficacy than any one mechanism can provide.

And so we are in the clinic. We're in a Phase I trial with healthy volunteer patients, and we are -- or sorry, healthy volunteers, and we're looking to read that out in the second half of this year. And we're very excited about that as our next program and in Dianthus.

Excellent. So you touched on this a bit. You had two very positive data readouts for claseprubart over the last year. Can you just go a little deeper, summarize the success that you saw in myasthenia gravis and in CIDP?

Sure. So myasthenia gravis in September was a very important moment because it was the first time we had actual patient data. And it was a small Phase II, but despite only having just over 20 patients in each arm, we tested 300 milligrams, our target dose and then a high dose, 600 milligram, we didn't see any efficacy difference. We knew there wouldn't be. The 600-milligram dose was really just there to reassure that we weren't going to leave any efficacy on the table and so on. But despite the fact that there was just over only 20 patients, and it was primarily a safety study, all the efficacy endpoints were secondary end points. It was really strong, robust, statistically significant data, whether you look at the MG-ADL or the QMG or multiple other efficacy measures. I mean, we had efficacy like within the first week and all the way through the 13 weeks. And very, very robust despite the fact that placebo patients had an outsized response. The placebo response was actually higher than we would have liked to have seen.

And the lesson learned there is we had an MG-ADL as a screening criteria. MG-ADL is a very simply question self-administered patient questionnaire. And -- but we didn't have a QMG. The QMG is, let's say, maybe a little more objective. It's physician administered and it takes up to 2 hours. And we didn't want to have that as a screening criteria because we were a young company. It was our first trial. We wanted to encourage people to put patients in our trial, and we thought this would make it too burdensome. But what we saw is that our placebo response was a little bit higher than we had hoped. And I think it was because some patients self-reported as being moderate to severe when maybe they weren't. And so of course, when they got placebo, they had an outsized response. We did a post-hoc analysis, and we said, what if we had a QMG screening criteria like other complement inhibitors had. And we saw that a placebo response would have been closer to 2. And then the separation from placebo would have been much more dramatic. And so we had very strong statistically significant data. The safety looked really great, and it confirmed that 300 milligrams every 2 weeks was absolutely the target dose.

What really excited us though, after when we did some of the post-hoc analysis and looked at some of the open-label data is it seems to indicate when we took patients who were on placebo and put them into the open-label portion of the trial, we didn't give them a loading dose. We started injecting them only every 2 weeks. And as the PK levels crept up to the target PK level of 300 milligrams -- what we achieved with 300 milligrams every 2 weeks, we saw that patients were having a really robust response on top of the already robust response they had in the blinded portion. And what that told us is that at PK levels, half of what we achieved at steady state with every 2-week dosing, we see a very strong response. That's the PK level we achieved at every 4 weeks.

So like I told you before, we always thought we were overdosing. And our open-label data seems to indicate that we don't need to achieve the high levels, the PK levels that we achieve with dosing every 2 weeks, that what we could achieve with every 4-week dosing will be enough. And then there was this independent data from Regeneron. They have a C3 inhibitor, cemdisiran. They read out in August, and they had a pretty nice robust response versus placebo. And what's interesting, we don't know a lot about the drug, but what they did reveal at that point is that they only achieved 75% inhibition of the classical pathway. We get above 90% inhibition with every 2 weeks. Every 4 weeks, we get above 75% inhibition. So what they proved is as a comp inhibitor, if you're just somewhere in the high double digits, above 75%, you're maxing out efficacy. So our every 4-week dosing should have a pretty good shot at being the same as every 2-week dosing. So we're taking both those doses into Phase III versus placebo.

But that was a big moment, obviously, and it reassured folks that, yes, active aC1s inhibition works and it is very well tolerated. Then we had the CIDP data in March. I think most people expected it would work in CIDP. So we had this interim responder analysis, we said up to 40 patients complete Part A, just to reassure people and let them know it's working. The reason people felt that it should work is because riliprubart, which is an active C1s inhibitor in Sanofi's pipeline. I think they're only pursuing CIDP. There are some other indications they might be doing some earlier studies in, but CIDP looks like to be the only indication. They had a really strong proof-of-concept Phase II study that showed somewhere around 50% of patients when switched off standard of care for CIDP would had additional benefit on riliprubart. And I think most people, like we expected that we would have similar data despite the fact that we're about 7x more potent.

What's interesting though, is what we started seeing in our open-label CIDP data is that we were seeing significantly better response rates than what riliprubart had demonstrated, meaning that our difference in potency in CH50 hemolytic assay, we weren't sure what that mean better efficacy. It definitely seemed to result in better efficacy at least in CIDP. So what that meant is that we got to our target of number of responders in the open-label Part A much sooner than expected. So we were able to make the announcement sooner than expected. And that, of course, really turned into [indiscernible] that's how we were able to raise that $719 million in the follow-on.

[indiscernible] at least from my perspective, where I stand now with Claseprubart is this antibody in my mind, is derisked. It works in neuromuscular conditions. We know in MMN it's going to work. Empasiprubart, the C2 inhibitor from argenx has shown proof of concept. They'll have Phase III data later this year. We are 7x more potent than riliprubart, and we showed better efficacy in CIDP.

In the assay that argenx used to demonstrate potency as a classical pathway inhibitor for their C2 inhibitor. When we replicate their assay and they were -- we're 38x more potent than them. Whatever efficacy data they show, we will at least be able to show that. Will we be better in MMN? We don't know. In CIDP, the answer seems to be yes, potency matters. We're not sure in MMN, we'll have to see the data.

So from my perspective, from an efficacy standpoint, safety tolerability, again, we're not done with all the trials, but it's looking really, really good. My focus with the team now is execution, just execute as fast as possible, get to market as fast as possible. Why? Because in MG, the market is evolving, still less than 20% of U.S. patients that are eligible for biologics, AChR-positive patients are on biologics, less than 20%. That market is evolving. And the sooner we can get out there, the more we can do with this asset with patients.

In CIDP at one point, riliprubart had a 3-year advantage. Now it's looking like it's less than 2 years. They'll have another update later this year. Every time they have an update, they delay their -- when to expect their Phase III data, we'll see what they say later this year. We'll have an update later this year on how our CIDP trial is going too.

I'd like to get that advantage down to a small kind of advantage as possible because every quarter, every few months that we can cut in their advantage just means more market share for us. So that will be -- that's why it's so important. And with MMN, of course, it's really just us and empasiprubart. So the sooner we can get to market [indiscernible] for Claseprubart and Dianthus. So that's [indiscernible] with 212, it's about making sure we understand what's the optimal dose in terms of risk benefit or in terms of tolerability and the PDs. We are looking to maximize the impact on type 1 interferon as well as on the B-cell side with the BAFF/APRIL side of 212. And so now our focus is on making sure we get that right and kick off the clinical programs in SLE, Sjögren's and Dermatomyositis as quickly as possible as well.

That makes sense. For MMN, in particular, so you've touched on this a couple of times. You have the data coming -- Phase II data coming later this year. Can you just talk a little bit more about what we should look for in the data? And why investors should be excited about that as a commercial opportunity?

Yes. And Look, MMN has been always a little bit underappreciated and living in the shadow of MG and CIDP. Now that we have those two big pivotal moments behind us, more attention is being paid time to MMN, which I'm happy about. And it really helps that argenx is also talking about MMN a lot more now. And we really, like argenx, believe this is a blockbuster opportunity. This is a 70% to 80% of physicians, if you talk to the neurologists that treat MMN in the U.S. will tell you, nothing really works that well. IVIg is not that effective, certainly not as effective as it is in CIDP, for example. And partly because of that, it's severely underdiagnosed. They agree 80%, I think, of the physicians we talked to said, it is definitely underdiagnosed.

So yes, it's smaller than the other two, but nothing really works. And there's only one other competitor. It's really only two biologics, two classical pathway inhibitors. Claseprubart with Dianthus and empasiprubart from argenx. So I think this market is a multibillion-dollar opportunity. I think in our size, we have at least a $5 billion market in the U.S. in biologics by 2035. So it's us versus empasiprubart.

So what are the difference between us and empasiprubart? Well, first off, we know we have a much more potent classical pathway inhibitor. So they're a C2 inhibitor. They block both the lectin and classical pathway. They finally published using the Quidel MicroVue CH150, what their potency looks like at the IC50, they didn't give the IC90. So we said, okay, that's their assay of choice. That's where they talk about their potency. So we use the exact same assay. We did a head-to-head with our antibody versus theirs. At the IC50, we got very similar numbers for them, so we know we're doing this right. It's very consistent results. At the IC50, we're about 6x more potent. But I think what you want to do is maximize your inhibition of the classical pathway to really make sure you're maximizing efficacy in any disease, especially one like MMN where we know classical pathway inhibition works.

At the IC90, we're 38x more potent. I mean that's really dramatic. I remind you, versus riliprubart, we're 7x more potent at the IC90, and we saw better efficacy in CIDP. In MMN versus empasiprubart, we're 38x more potent at the IC90. I can't say yet whether that means better efficacy in MMN. We'll have to see what the data looks like. But we have a much more pone antibody. We don't touch lectin and alternative pathways that the precedent for this mechanism, C1S inhibitor, Enjaymo, Sutimlimab is out there and approved for cold agglutinin disease, and it has no box warning, no REMS. I believe if you block the lectin pathway, you're going to inhibit the complement system's ability to fight against the risk of infection. So it's very likely going to end up with a box warning, just like alternative pathway inhibitors have it, C3 inhibitors, C5 inhibitors, et cetera.

So it's very likely they'll have a box warning, and we won't. And then finally, they're an IV. I don't know what dose every month. But it's a dose they did not, I don't think, a test in Phase III. They had 10- and 30-milligram per kg once a week or once every 2 weeks in Phase II, but they're testing a once-a-month IV and I don't think they've disclosed what dose in their Phase III for MMN. So we'll obviously have a more convenient option because we're testing 300-milligram, 2-milliliter every 2 weeks self-administered auto-injector. So that's it. That's going to be the competition. Will we have similar efficacy? We'll see. Safety, I think we'll have an advantage on box warning. And then certainly on convenience, we will have a better option for patients with MMN.

So I think this is definitely a multibillion-dollar market opportunity that we will layer on top of CIDP and on top of MG, all with one target, neuromuscular specialists and neurologists in the market. So I'm really excited about it.

So we have this data coming later this year. In terms of what to expect from our data, we have to remember, this is a very small study. There's only 12 patients per arm. We're testing 300, 600 and placebo. So it's primarily a safety trial. And I can tell you, from a blinded perspective, it's looking very consistent with what we saw with MG and CIDP. So very reassuring. Yes, we're looking at some efficacy endpoints, like grip strength, so on and secondary endpoints. But this study is far from being powered for stat's sake. And I know I said that for MG, but MG was almost twice the size of this trial per arm.

So really trying to manage expectation. All we're looking is for signals and trends that look right in efficacy. We really want to move to Phase III as fast as possible. Empasiprubart has shown that classical pathway inhibition works, and we hope that they'll have really good data when they report out their Phase III in the fourth quarter.

There will be the inevitable temptation to compare our Phase II to their Phase II, their ARDA trial that read out a couple of years ago. I'll caution, again, there's a couple of reasons why you can't do cross-trial comparisons for other than the obvious -- other than the obvious reasons. One is it's a smaller trial. We have a much smaller trial. But secondly, they really focused on how patients on empasiprubart didn't need as much IVIg rescue as placebo patients. I think it was somewhere around 90% reduction in the need for IVIg rescue. We obviously are looking at that as well, but that endpoint is now irrelevant. The primary endpoint in Phase III is grip strength.

But the reason you can't compare whatever we're going to show in terms of percentage of patients who required IVIg rescues is because empasiprubart, if you have a deteriorated by at least 2 points on the MRC-10 or 30% on grip strength, that meant they saw clinical deterioration, you would get IVIg. But they also had another element. If a patient just asked for it, we don't have that. We have the MRC. We have the grip strength to define clinical deterioration. But if a patient just asked for the IVIg, we didn't. That was not enough to give it to them. So obviously, they had some patients on -- not an insignificant number of patients on placebo that asked for IVIg, even though they weren't showing clinical deterioration, and we're not -- we won't have that. So you're not going to be able to compare percentages. So I just caution on that.

But essentially, what -- like I said, what we're looking for is dose the efficacy -- sorry, does the safety tolerability look the same as what we've seen previously in MG, CIDP and what we're seeing currently in CIDP? Yes, perfect. And then are we seeing some trends, some signals on the efficacy that we expected. And really, the job for the team is going to be to get to a Phase III as fast as possible.

Excellent. Let's talk a little bit about commercial dynamics then in CIDP. You touched on competitive landscape in MMN. Let's just talk for a second about competitive landscape for complement approaches in CIDP.

Yes. Look, I think a lot of investors are very excited about CIDP, and it makes sense. There is a treatment paradigm change coming in CIDP. That's pretty significant. Up until very recently, IVIg was seen as the gold standard in efficacy. And frankly, it still is. It's still seen as the most effective treatment for CIDP. Efgartigimod is a very nice novel innovation for CIDP patients, but it's inferior to IVIg on efficacy. It's just a much better tolerated, much easier-to-use version of IVIg, but not as effective.

So I think that's why, for example, you didn't see, I think, any company studying FcRns, won't study refractory patients to IVIg, because if IVIg didn't work, it's very unlikely efgartigimod or any FcRn will work. So it's clear that IVIG is still the most effective treatment, and now we have a nice option for patients who may be naive, try efgartigimod first because if they respond, fantastic. It's much better tolerated and easier to take than IVIg. So that's great. Maybe if a patient couldn't tolerate IVIg at all, you try efgartigimod. But if a patient doesn't respond to IVIg or they respond really well to it and can tolerate it, there's really no other option.

What we saw with riliprubart in their Phase II, and we're seeing in our open-label Phase III portion of our Phase III trial is that classical pathway inhibition seems to be more efficacious than IVIg. Patients who are on IVIg or standard of care and stable or refractory to IVIg or standard of care, switched immediately to riliprubart, you saw about a 50% improvement. We did the same thing, we switched immediately within 7 days to Claseprubart, and we're seeing materially better results. Again, I spoke to the potency differences earlier. It seems to be translating to better efficacy so far. We'll see at the end of the trial if those numbers hold up, but it's looking very promising.

So when I look at the CIDP market in the future, what I think we're going to see is that classical pathway inhibition is seen as the most potent, effective way to treat CIDP, than IVIg and then FcRn. Now which one will be used first, second, what will be the -- how will physicians tackle CIDP patients? We'll see. But I think if you have a more -- clearly more effective treatment that's much better tolerated and safer than IVIg and certainly a lot more convenient, I don't see how classical pathway inhibition won't be the first line.

And like I said, up to this point, the efficacy we're seeing looks superior to riliprubart. It looks superior to the other active C1s inhibitor, and I think it's because of that potency difference. So it may be that the most effective treatment will be Claseprubart, then riliprubart, then IVIg and then FcRns, below that. And where does empasiprubart fit in there? I don't know. We have to see some data at some point. and CIDP. But certainly, in terms of its potency around classical pathway inhibition is the least potent of the 3 complement inhibitors, riliprubart, us and [indiscernible] the least potent. So I don't know what that will mean in efficacy, but right now, it looks like the more potent you are, the more efficacy you have.

Excellent. Let's then move -- shift gears a little bit to myasthenia gravis. Can you talk a little bit more about the Phase III design and some of the enhancements that you made based on what you saw in the Phase II?

Yes, I kind of hinted at it earlier. So the first thing is we are going to have a QMG screening criteria. We're going to try to keep that placebo response down to what we've seen historically around a 2-point improvement, so we can let the antibody really do -- show what it can do. We're testing, of course, 300 milligrams every 2 weeks, 1 shot every 2 weeks, [indiscernible] like a DUPIXENT, exactly the same dosing administration as DUPIXENT. And then we're testing it once every 4 weeks. So we are making the trial larger, but we think it's worth to test that every 4-week dose because, again, as I mentioned, the open-label data, the cemdisiran data for Regeneron, everything is telling us that just north of 75% inhibition, PK levels are half of our steady state at 300 milligrams every 2 weeks seem to look like it could be just as efficacious.

And that trial, we said would start midyear. Everything is on track to get that study started. The part that I'm most excited about is we had a regulatory update after our CIDP announcement, where we agreed with the FDA that looking at ANAs, testing for ANAs, screening out for high ANAs or even double-strand DNA is irrelevant, right? That was just something to look at in Phase II, but we should not bother with it anymore. It doesn't mean anything. Our #1 reason for screen failures in MG, and the reason we weren't able to report out our data even earlier than when we did, is because MG patients just have high ANAs. And so we had a huge amount of patients that basically couldn't come into our trial, very frustrating for the investigators, for the patients, for us. We couldn't put them in our trial because of their very high levels of ANA.

That's gone now. We agree that we don't need to track it. We don't need to screen for it. It's irrelevant. That should help between the enthusiasm we're feeling with our investigators from our -- because they've seen the Phase II results from MG. They're hearing about the CIDP results because it's open label. So everybody -- they're talking to each other. It's a small community, the neuromuscular specialists. I think we have a really good chance of meeting or -- certainly meeting the timing expectations we have for data in the second half of '28. So that trial, we're really excited about, and everything is going really well. The team is just doing a phenomenal job on execution.

And how do you see the commercial market playing out in myasthenia gravis? Is that more crowded FcRns have a foothold? What's your prospective?

For sure. It's the most crowded of the three indications we're going after. But I want to point out a few things, and argenx is saying this as well, which I'm really happy to hear, less than 20% of patients who should be on biologics in the U.S. with MG, are on biologics. This market could easily be 2 to 3x larger. So it's not just about competing for market share. It's about growing this market. And what does the market need to grow? Well, if you look at autoimmune markets and historically, what got them to 40%, 50% penetration of biologics, you got to make it really easy, an auto-injector, no box warning, just really simple, good efficacy. That's what Claseprubart offers. And we'll see if anybody else can offer the same combination of those three things: efficacy, safety and the convenience of an auto-injector self-administered infrequently.

The other thing is, well, UPLIZNA is just launched from Amgen. I mean that -- it takes months for that to kick in and really show any efficacy if it does show efficacy. It's got a side effects on the tissues. The big advantage is simple is it's once every 6-month IV. That's really nice. It's very convenient. Patients don't get these drugs if you have MG for convenience. They're not -- they're looking for efficacy. So despite this less than ideal profile, I think it's beating expectations. And I think it's because, again, even with -- it's being used second line, by the way, mostly. Even with the FcRns out there, even with the underpenetration of biologics, there are a lot of patients out there who are just looking for more options. And that just proves it. So for me, the MG market, people feel like, oh my God, that's it. It's over, FcRns on it. Not really. There's a huge potential for growth, and there's still a lot of patients out there that are not satisfied with what's offered.

So even in the worst-case scenario where you assume Claseprubart as a second-line option to FcRn, which I do not believe is going to be the case at all. I think we're going to have a very nice first-line position in MG. It's still a multibillion-dollar blockbuster. And then just add on top of that CIDP and MMN, I mean the numbers -- it doesn't take much to get to a multibillion-dollar peak [indiscernible]. I think with MG, it's about continuing to grow the penetration of biologics, continue to educate physicians on why we should be treating those patients earlier, faster with biologics. And then just having more options that are very convenient, safe and with good efficacy.

Excellent. Switching gears then just to the 212 asset and the rheumatology franchise. You mentioned the in-licensing, how it came into Dianthus and the prioritized indications. Maybe just touch a little bit on clinical development plan and how you're thinking about pursuit of those indications in the months ahead.

Yes, we're very excited. I mean it looks at least similar or better in terms of pDC depletion and type 1 interferon reduction to Litifilimab on one side, on the BAFF/APRIL, the Ig reductions look like the midyear is like deeper and longer than pove, so we could have a nice infrequent biologic in our hands here with a best-in-class, both BAFF/APRIL and BDCA2 inhibitor. So right now, the goal is to figure out what's the right dose. We're taking two mechanisms, putting them together into one bifunctional fusion protein. It's about figuring out how do we maximize the PDPK, while also making sure that we manage for any potential tolerability or safety signals.

So that work is ongoing with healthy volunteers. We plan to report out what we found and what doses we think we have planned to take into the Part B of our Phase I trial, which is SLE patients, and potentially to MAD or Phase II studies as quickly as possible. That's really the next step. We're very excited. We're working with Leads, our partner in China, the Phase I study is being done in China. And yes, I'm very excited about the potential here for 212. If we can get to that optimal PD profile and dosing profile, without any significant new safety or tolerability signals that kind of change the risk-benefit profile, then this drug could be really, really big. It will be a nice way to build the company over the next few years on top of Claseprubart as our foundation.

Excellent. Last question here, just keeping an eye on time. You're very well funded. You talked about $1.2 billion of cash and runway into 2030. You're in a great spot. Can you just talk about your focus areas for this year and just general aspirations for the company?

Yes. Look, what we -- from the very beginning, this has been about building a very exciting, independent, self-sustaining biotech autoimmune company focused on rare diseases for now over the long term. And pipeline has always been a priority. And so I'm very, very pleased with where we are today. There's more to do and stay tuned for any future developments there.

But the immediate focus, like I said, Claseprubart about execution, just speed and quality, not or both. And it's to be able to get this option to patients as quickly as possible in the market and therefore, be able to be part of that solution to growing the penetration of biologics in MG and change the treatment paradigm in CIDP and potentially in MMN. And with 212, again, it's just making sure we 0 in on a tight range around dosing to take into the MAD Phase II portion, and get moving as fast as possible. And now that we have the cash, potentially try to do as many of these -- as many of the pivotal trials in parallel as quickly as possible with the team and build a really nice rheumatology franchise there to complement our, no pun intended, our complement inhibitor in the neuromuscular space. That's our primary focus. The team is growing. We're doing really, really well. I'm just really, really eager to see how the company develops in the next couple of years. But it's been a fantastic 5 years and the way we've grown every year, and I expect that we're going to continue that trajectory in the next few years.

Excellent. Thank you again for the time.

Thank you, Matt. Really appreciate it.

Good morning, and welcome to the Dianthus Therapeutics Conference Call. My name is Michelle, and I'll be your operator for today's call. A slide presentation to accompany the call is available on the Investors section of the Dianthus Therapeutics website. Following the company's prepared remarks, we will move to a Q&A session. Please note that today's call is being recorded. I will now turn the call over to Marino Garcia, CEO of Dianthus Therapeutics. You may begin.

Thank you, operator. Good morning, everyone, and thank you for joining us today. Earlier this morning, we issued a press release with our early go decision for the interim responder analysis for our CAPTIVATE trial in CIDP, and we are thrilled to share with you more today on this call. This earlier-than-anticipated announcement reflects the Dianthus team's commitment and passion for patients suffering from severe neuromuscular diseases.

And I'd like to take a moment to thank them for their hard work. Specifically, thank you to the clinical development team, to the clinical operations team working on CIDP and all the supporting players across the organization that are making this exceptional execution possible. I'm very proud and grateful to be part of this team. Just a note before I begin the presentation, we will be making forward-looking statements, and I would refer you to our SEC filings for more information.

Next slide, please. I'm joined today by Dr. Sim Randhawa, our Head of Research and Development; Ryan Savitz, our Chief Financial and Business Officer; and John King, our Chief Commercial Officer. I'll begin with a few introductory remarks about the CAPTIVATE trial and best-in-disease potential we see for Claseprubart in CIDP, 1 of 3 neuromuscular conditions we are pursuing. Next, Sim will review our interim responder analysis for the CAPTIVATE trial.

Finally, I'll discuss the opportunity we see for Claseprubart in CIDP and upcoming milestones. Then we'll open up the line for questions. Two slides forward, please. I'm overjoyed to be here to discuss the planned interim responder analysis and our early go decision to continue the CAPTIVATE trial, evaluating Claseprubart in CIDP at 300 milligrams, 2 milliliters every 2 weeks.

A reminder that CAPTIVATE is an ongoing single 2-part Phase III pivotal trial and is designed to support a [ BLA ] in adults with CIDP. Because it is ongoing, we are unable to share specific data and responder rates for Part A at this time as we must protect the integrity of this pivotal trial. We will aim to provide some color and context of protecting the patients in this trial is our priority.

As a reminder, Part A is open label, where patients who are standard of care naive, stable or refractory are dosed or switched within 7 days to a single subcutaneous injection of Claseprubart at 300 milligrams 2 milliliters every 2 weeks for up to 13 weeks. Then only patients that improve by at least 1 point on the INCAT score for 2 visits in a row over their baseline starting at week 5 can then move on to Part B.

Part B is the randomized withdrawal double-blind, placebo-controlled part of the trial. Today's announcement is an early go decision based on the planned interim responder analysis in Part A of the trial, which Sim will speak to in a few minutes. Now for some of you, CAPTIVATE will look very similar to ADHERE, the trial evaluating efgartigimod in CIDP patients, which resulted in a broad label for the treatment of all adults with CIDP.

As you know, we generally cannot make cross-trial comparisons, obviously. And in this specific situation, it is even more difficult due to 3 very important differences. Please next slide. The first difference is CAPTIVATE allows patients who are refractory to IVIg or standard of care to enter the trial. ADHERE did not. We strongly believe that active C1s inhibition will provide additional benefit above and beyond what IVIg could do for these patients based on the impressive improvement seen with riliprubart in their open-label trial.

Secondly, ADHERE withdrew IVIg, making patients wash out from their treatment and relapse before allowing them to enter their open-label Part A. Patients had to deteriorate in a clinically meaningful way before they were allowed to be dosed with efgartigimod. CAPTIVATE doesn't do that. Like other complement inhibitor trials in CIDP, including riliprubart's proof-of-concept trial, CAPTIVATE switches refractory or stable patients from their Ig treatment within 7 days without a washout or making patients relapse. And then the third key difference is CAPTIVATE Part A defines a responder as a patient that improves above and beyond their baseline.

Our goal was to see at least 40% to 50% of stable and refractory patients improve by at least 1 point on the INCAT score above and beyond their previous therapeutic regimen, including IVIg after an immediate switch and without causing a relapse.

ADHERE demonstrated a 67% response rate. But you need to keep in mind, this response rate means only 2/3 of patients were able to recover or approach their baseline scores after they were made to relapse. 1/3 of the patients were not able to recover from the relapse. So why were we targeting approximately 50% responder rate with our Part A? This is based on the impressive precedent data set for active C1s inhibition in CIDP. Next slide, please.

This is the proof-of-concept data I'm referring to with riliprubart, which is currently in Phase III for CIDP. This open-label trial enrolled CIDP patients that were naive to or stable on standard of care as well as patients that were refractory to standard of care and switched them within 7 days to riliprubart. In the group on the left, these are patients who are stable on standard of care, including IVIg, were switched to riliprubart and 52% did even better than how they were doing before.

Again, this is switched within 7 days. In the second group, patients were refractory to standard of care in IVIg. These are patients with no real alternatives today to IVIg if it didn't work. Here again, 50% of patients improved when switched to active C1s inhibition. These are the patients that here did not allow into their study. This trial seems to suggest active C1s inhibition may provide a benefit for a significant percentage of patients above and beyond what today's standard of care therapy could achieve.

The third group on the right are the standard of care naive patients, and not surprisingly, the responder rates there look even more impressive. I will remind you that the dose for riliprubart in this trial and in their Phase III trials is 600 milligrams, 4 milliliters every week. We are evaluating Claseprubart at 300 milligrams, 2 milliliters have to dose a single subcutaneous injection every 2 weeks.

So in other words, they're dosing 4x more drug than Claseprubart. And if delivered in a 2-milliliter auto-injector, it would mean 8 shots a month for riliprubart versus 2 shots a month for Claseprubart. So how does this data inform our objectives for Part A of the CAPTIVATE trial? Next slide.

With Part A of CAPTIVATE, the threshold for the go decision at 300 milligrams, 2 milliliters every 2 weeks was to see a confirmed response in the 50% range with patients or 20 out of the first 40 patients that complete Part A. This target was based on the approximate 50% response rate benchmark we saw with riliprubart in their open-label trial. Next slide.

With this, I'll now hand it to Sim to take you through the update and provide a little more color and context around our early go decision. Sim?

Thank you, Marino. The medical team is very motivated to get the primary results as quickly as possible based on what we have seen in Part A so far. I would like to emphasize that our interim responder definition was a very high bar to meet because it required an improvement in INCAT over baseline, a high efficacy metric to achieve.

In addition, this INCAT response needed to be confirmed at 2 consecutive visits, 2 weeks apart and could not occur prior to study week 7, eliminating therapeutic overlap with discontinued medications. Our go intention targeted an INCAT response rate of 40% to 50% in 40 patients who completed Part A based on Phase II riliprubart CIDP data. This means the upper end of our target was 20 INCAT responders. We hit this target prior to 40 patients completing Part A.

On the safety front, we continue to be reassured on the Claseprubart safety profile with no concerning safety events recorded, including no clinical symptoms of autoimmune activation, concerning bacterial infections or study discontinuation for safety or tolerability issues. Next slide. As you can see in these pie charts, the patients studied in CAPTIVATE and riliprubart Phase II are quite similar based on treatment bucket. I will add, our results were not driven by a specific patient subgroup such as geography.

Next slide. Now let's switch gears to how the interim analysis has informed positive changes to the CAPTIVATE study design. First, Part A remains unchanged. We will continue to evaluate 300-milligram subcu Q2 weeks. Second, we see no need to evaluate 600 milligrams in Part B. So we are dropping that arm and Part B will now be a 2-arm blinded RCT evaluating 300-milligram Q2 weeks versus placebo.

Third, we are raising our Part A responder target from 40% to 50%, which we feel is a comfortable bar to meet. The implication of these changes are a substantial reduction in Part B patients needed from 192 to 128 and a greater reduction in Part A patients dosed from 480 to 256. Next slide. Finally, we have the revised study schematic showing our updated CAPTIVATE study schematic with a 2-arm Part B and our Part A responder target increased from 40% to 50%. And with that, I'll turn it back to you, Marino.

Thank you, Sim. Now moving to Slide 15. Today's update continues to build on the promise of Claseprubart as a potential pipeline in a product and best-in-disease therapy in growing and underserved neuromuscular markets. We announced impressive robust results in generalized myasthenia gravis with our MaGic trial in September last year.

And today, we have a milestone moment with an early go decision for our CAPTIVATE trial in CIDP. We look forward, as Sim said, to completing this trial as quickly as possible. We will provide guidance for when to expect top line results sometime later this year. And CIDP is a multibillion-dollar opportunity for Claseprubart because of the significant unmet needs that remain for patients. Next slide, please. The CIDP market is a large and growing multibillion-dollar market with an estimated 40,000 patients in the U.S. alone.

The unmet needs in CIDP remain high and significant, including the need for more efficacious, better tolerated and more convenient options. Next slide, please. This conclusion is supported by recent market research we conducted with a survey of 80 neurologists that treat CIDP in the U.S. What we heard clearly from them is they want new therapeutic options that provide 3 things: one, greater efficacy with more consistent, sustained symptom control; two, safer and better tolerated options with no box warning or REMS; and finally, more convenient, easier to use, ideally a self-administered therapy.

Next slide. IVIg is still considered the most effective therapy on the market today for CIDP patients. And yet when we specifically asked these neurologists how they felt about IVIg, we found that 3/4 of neurologists surveyed told us they need therapies that can help patients that are refractory to IVIg as they don't have any effective options for these patients available today. And more than half told us that their patients on IVIg experienced waning efficacy before their next dose, suffer a high treatment burden due to frequent and time-consuming infusions and that they are concerned about IVIg's box warnings.

These overall needs are what Claseprubart aims to address effectively. Next slide, please. The target product profile for Claseprubart in CIDP aims to be a potentially best-in-disease therapeutic. Our goals are to achieve efficacy that compares favorably to current standard of care therapies like IVIg with a safety and tolerability label similar to the first-generation C1s inhibitor Sutimlimab or Enjaymo, which has no box warning of REMS and finally, with the Dupixent-like convenience of a one-click self-administered fast auto-injector dose once every 2 weeks.

Next slide, please. With today's update, we're well on our way to building a powerhouse neuromuscular franchise where Claseprubart can compete effectively as a first-line biologic in 3 growing markets with over 150,000 patients in the U.S. alone. As I mentioned earlier, we have reached 2 important milestones in building our position in MG and CIDP, and our next step is to read out our Phase II MMN trial in the second half of this year. Next slide. So looking ahead, this will continue to be a catalyst-rich year for Dianthus. We announced this morning, we plan to initiate our Phase III trial in MG in mid-2026, evaluating 300 milligrams every 2 weeks as well as 300 milligrams once a month versus placebo. Top line results are expected in the second half of 2028.

And we continue to expect, as I mentioned, top line Phase II data from our MoMeNtum trial in MMN in the second half of this year. We also look forward to argenx's Phase III results for empasiprubart in MMN later this year, which should have very positive read-through to us.

For DNTH212, our new clinical stage bifunctional fusion protein targeting BDCA2 and BAFF/APRIL, we expect to announce indications we will be prioritizing in the first half of this year and then announce top line results from our Phase I healthy volunteer study in the second half of this year as well. As a reminder, we have a very strong balance sheet with a cash balance of approximately $514 million as of December 31 to fund operations into 2028.

Please turn to Slide 22. And with that, let me close with this one comment. Today's announcement is a double upside scenario for us. Not only did we hit our target number of responders much earlier than expected and hence, the reason we are here with you today ahead of our already accelerated guidance of Q2 this year. But I want to point out that moving our baseline conservative assumption of responders required in Part A from 40% to 50% is a huge change and a signal of our confidence in the data we are seeing. We went into this trial assuming success with a 40% ratio in Part A, expecting to see similar efficacy to riliprubart.

The fact that we are changing it to 256 patients or a 50% ratio on top of a go decision signals very strong confidence in the data we're seeing. With that in mind, thank you, and let's open it up for questions.

[Operator Instructions]. Our first question comes from Yatin Suneja with Guggenheim.

Congratulations on the data, really good results in our perspective. So 2-part question. So first is, I mean, you are showing that the patient population is very similar to riliprubart. And despite that, you're able to produce -- or it seems like the efficacy is better than riliprubart. So could you talk about what your hypothesis is, what is driving the superior data relative to riliprubart? And then Marino, you just made a comment on change in this percentage to 50% now.

I know you cannot disclose the data, but could you articulate like if you see, let's say, something in the 40% to 55% responder rate, would you have changed that? Or does that need to be meaningful higher than your assumption for you to make that 50% change?

Thank you, Yatin. On the first question, let me hand it to Sim to provide his perspective.

Yes. So I think the -- to summarize the question was why do we think we're seeing data that kind of beat our expectations, which were largely based around what we saw with riliprubart's data. I think there are 2 possible explanations. One is, I think we're seeing that the hypothesis of classical complement pathway inhibition upstream seems to be real. Now we've seen it twice.

So we know that the mechanism is behaving well in this patient population. And then, of course, we know that we are a far more potent product, which means that we are probably delivering more upstream inhibition than they're able to. So that's one hypothesis. The other hypothesis again is I just want to caution everybody, like we are releasing an interim analysis. This is in a meeting but a small number of people. So we designed an interim at a time when we thought it would be informative to the study. So again, that should mean something. But again, it is in a relatively small number of people. So it is -- so I just want to make sure that, that is also well understood.

Yatin, on your second question, I think what you're asking is if the response rates we had seen were somewhere in the 40% to 55% range, would we have changed it to 50%? No. We needed to see a substantially higher response rate than that to move that 50%. That 50% is a conservative number to make sure that we absolutely don't risk under enrolling Part B.

Our next question comes from Alex Thompson with Stifel.

Congrats on the data. Maybe 2 quick ones. I guess for the subpopulations here, maybe could you comment on whether you're seeing response rates that are sort of consistent with what you would expect based on the riliprubart Phase II? And then could you also comment on sort of what it is to define a responder in your study versus the riliprubart Phase II and how that might be more rigorous or not?

Surely. So I think what we've suggested is that the response -- the overall response rate that we're seeing seems to be higher than what we've seen previously. So what that would imply is that in each of the buckets, the response rate was somewhat higher, and that is true. In terms of consistency between where we expect the response rates to be highest, I would say, yes, that's largely true, and we want to see that.

So in those patient populations where you would expect a slightly higher response rate, that's exactly what we see. If we didn't see that, we'd actually be concerned about our data set. So we're actually pleased to see that. The second point around the rigor of the actual endpoint. So the INCAT is a relatively high efficacy metric to move. So if you look at the possible different efficacy metrics in CIDP that you can approach, right, there's the INCAT -- there's the I-RODS, there's the MRC or the muscle Sum score, there's grip strength. Those are generally the ones that you think about.

Of those, the hardest one to move is really the INCAT. It takes the most improvement to move it. So in and of itself, it's pretty rigorous, and that's what was used in the riliprubart trials as well. In our specific case, because this is a registrational study and not just a single open-label study, we really tried to make sure that the responses we were seeing are valid because, of course, we want to have a positive Part B, not just a pleasing Part A.

And what that means is we required confirmation of the INCAT at a subsequent visit and that confirmation could not happen prior to week 7. So what that means is that if you came in at week 5 and you were an INCAT responder, you had to confirm that response at week 7. You could not simply revert back to baseline and then confirm the response at a later visit. It had to be on 2 consecutive visits. The other thing, of course, is the medical team. We took great pains to make sure that what we were seeing on the INCAT was actually consistent with what was happening on the other efficacy metrics. So we didn't just sort of check box off an INCAT responder and say, great, we looked and made sure that whatever the patient said they improved on was reflected on what the physicians saw in their physical exam.

Our next question comes from Pete Stavropoulos with Cantor Fitzgerald.

Marino, Sim, Ryan, and team, congratulations on the outcomes. So one question that I have is the dosing window for Part A is up to 13 weeks of treatment. Will you miss some of the patients and therefore, reduce the reported responder rate when Part A is completed? And the reason I ask is when you look at the riliprubart data, there is continued deepening of benefit and some patients had not crossed the 1-point threshold on the INCAT by week 12 and 16.

Pete, that's a great question. I'll ask Sim to add some comments there. But yes, it was a higher hurdle. We would not count anyone, obviously, after 13 weeks. So we are only counting responders who respond 2 weeks in a row starting at week 5 to week 7 and so on. But yes, if someone needed 15 weeks, 16 weeks to respond, they weren't counted as a responder in our analysis.

Yes, I don't have much more to add to Marino outside of saying that this was something we paid attention to during the course of the study. And on the table was always extending Part A if we thought that, that was needed. Fortunately, for us is we saw a very hefty responder rate, so we didn't feel the need to do it. But I think, obviously, if we extend it out to 24 weeks, any rational human being would assume that we would -- our response rates would go up a little bit.

Yes. And look, part of why we thought 13 weeks was enough and felt like that higher hurdle was not a problem for us is the data we saw in MG. I mean it's just very rapid, robust, quick response in patients with neuromuscular conditions. And the data that we're seeing in CIDP is consistent.

Our next question comes from Gavin Clark-Gartner with Evercore ISI.

Congrats on the great outcome. I just wanted to make sure I heard you correctly on safety. There was no drug-induced lupus, no autoimmune symptoms, including lupus, and I think no other signs of autoimmune activation. And then just quickly on the sample size. For Part B, was there any consideration to lower the sample size below 256? Or was this really the lowest you wanted to go?

Yes. Sorry, Gavin, you're talking about -- you said Group B, but 256 is Group A. Which one are you referring to, the 128 in B or the 256 in Part A?

The 128 in B, sorry.

Yes. I'll ask Sim to comment on those.

Look, the safety remains very pleasing, right? In terms of what we saw clinically in MG, a very clean study, and that remains true now in CIDP as well. And of course, as you start to get more and more experience with the drug and a greater number of people now across 2 indications, we feel more and more confident on what the ultimate safety profile of this drug is. And yes, I will confirm there were 0 indications of anything that would lead somebody to believe in any autoimmune activation, let alone [indiscernible] , right? So very, very clean from that standpoint.

In terms of going lower in Part B, I think it's a registrational study, right? So sponsors always kind of tend to become very, very conservative in their assumptions because you've got one shot at getting this done correctly. And you want to make sure that in trying to reduce sample size, you don't somehow end up with a study that fails. And so it's my way of telling you that, yes, if we look deeply, probably you could shave some numbers off here or there based on common sense. But I think it's a small price to pay to over enroll a little bit to make sure that the molecule is allowed to show exactly what it needs to do.

Our next question comes from Yaron Werber with TD Cowen.

As well for me really for the terrific results. Two questions. One is just a follow-up on Gavin's question. For the Phase III gMG study starting midyear, can you -- it sounds like you've been in discussions with FDA about whether you need to do ANA monitoring and you can exclude patients with baseline ANA titers. Can you give us an update on that? And then secondly, it sounds like in Q2, we're going to get an update on the [ DNTH212 ] and potential indications. I think you've talked in the past about cutaneous lupus, lupus nephritis, SLE, dermatomyositis and Sjogren's. How should we think about? Would you only prioritize one? Would you run 2 Phase IIs, 2 different indications at the same time? Any thoughts would be great.

Yes. Thank you, Yaron. So on the MG trial, yes, we had a very, very productive, very fast, very short meeting with the FDA. We're just waiting for the minutes to come in. They're imminent and make sure that we have everything that we agreed to in black and white. So we'll provide more details and updates on the MG trial in the very near future, near term.

On the second question, which I'm now trying on 212, yes. Well, I mean, you named the 6 indications that were made the short list. You should expect that we're going to announce 3 that we're interested in pursuing as quickly as possible.

And then at some point later this year, potentially what exactly is going to be the rollout, what phase, et cetera, et cetera. But yes, the 3 -- we're going to mention 3 that we prioritize from those 6. Does that answer your question, Yaron?

Our next question comes from Rami Katkhuda with LifeSci Capital.

I wanted to pass along my congrats on the update as well. I guess any hypothesis as to why you've been able to accelerate enrollment of your CIDP study while Sanofi has announced delays? And then secondly...

Yes, I think... go ahead, Rami -- finish up.

I was going to say, based on the results in MG and now CIDP, do you also expect to drop the 600 mg dose of Claseprubart in MMN? Or is there a need for greater complement inhibition in that disease?

All right. Great. Thank you, Rami. So one thing, yes, on your question about, look, they're having delays with their recruitment. They say it's because of recruitment. We're not seeing that issue. I think there's 2 things I've mentioned to investors that I think were very helpful.

One is we designed this trial for multiple reasons. And one of them was that we knew that it would be very competitive out there. CIDP is a rare disease, and yet there are multiple pivotal trials going on with multiple sponsors. And so the idea was how could we make our trial more attractive for patients? How could we make it the ideal type of trial for patients to enroll into. And so when we saw the results of the ADHERE trial and we saw the results of the label, getting a broad population across all adults with CIDP despite, for example, not having any refractory patients in their trial, we thought this would make the best sense.

So if you're a CIDP patient looking at multiple trials and trying to decide which one you want to go into, if you're eligible, most trials, you go in, you're blinded right from the start, you could get placebo, you could get -- continue on IVIg, which obviously you're motivated to get off of, and that's why you're going into a clinical trial or you might get a drug that you don't know if you're even going to respond to it versus with us, it's just open label.

You just come in and you only have to come in every 2 weeks as opposed to every week, for example, riliprubart, you have one shot, and you see exactly what's happening. And only if you get better above and beyond your baseline, then you get randomized.

And yes, there's a chance you get placebo there. But even then, we want you like a hawk and the moment you relapse, we pull you out, rescue you and you get a chance to go back on the drug that you know you responded to in Part A and get that for up to 2 years for free. So it's just a much more patient-friendly study. So I think that has a little bit to do with it. I'll let Sim to maybe add anything. But clearly, our team is just executing at a really impressive level. They've done -- they're doing it across all programs in the company, not just CIDP. Do you want to add anything?

Yes, I don't have anything to add to what you said on the first question. On the second question, which regards the 600-milligram arm in MMN. I think that -- first of all, I think the CIDP data, because of the nature of the 2 diseases, right, which seem to be more upstream complement driven than perhaps others.

I think the CIDP results really magnify the probability of success in the MMN study, frankly. And then regarding the dosing. Intuitively, we've dropped 600 mg. We've now dropped it in CIDP. It would seem to make sense to drop it in MMN. The issues are -- there are a couple of issues there. Number one is we're already well advanced in that study, right? We didn't have a lot of people randomized in CIDP, so we could go ahead and drop the arm. But in MMN, we're well advanced in that study. Number two, out of all 3 indications that we're in with 103, MMN is the most underserved. There are actually no targeted options. I don't consider IVIg a targeted option for an autoimmune disorder. So there are no targeted biologic options in MMN.

So this is the one shot that we have to just make sure that we deliver the very best efficacy possible. And we don't know enough about MMN. We have no data there. There's just scan data available period. So the medical team has really decided actually a while back that we'd like to proceed with both arms in MMN.

Our next question comes from Maury Raycroft with Jefferies LLC.

Congrats on the update. Wondering how many patients you estimate could be enrolled by the end of this year? And what type of guidance you'll be able to provide for Part B at that point? And will you be able to announce when you've achieved the 128 responders needed to complete Part B?

Thank you, Maury. Yes. So we're not going to give any guidance right now on what our targets are for this year. Suffice it to say that every target we set for this trial, we keep beating, which is a nice situation to be in. But yes, sometime later this year, we'll provide guidance on when exactly we expect top line results for the entire trial.

I mean, frankly, for myself, I think for Sim, we'd want to see at least 100 patients in complete Part A before we really got comfortable with our estimate so that we don't sandbag or overpromise on when we expect top line results.

The other thing I'll add there is we didn't hold back on the study whatsoever, right? We took a very global approach to where we're going to go. We were not at all conservative in terms of the number of countries or the number of sites that we wanted to approach because we knew how many patients would be required, especially when we still had the 600 arm in play.

And we knew how competitive the market was and that CIDP patients aren't a diamond dozen either, right? So we went pretty broad. And what that means is that when you go broad, different countries have very different start-up times. And so part of the reason why we're not giving you guidance is, frankly, we still have some very meaty geographies that are just opening up this week. So we haven't really had time to let them enroll and see what they're able to do. And until we do that, it's hard for us to come out and just give you a date.

Yes. So was there another part to your question?

No.

Yes, that was helpful.

Our next question comes from Danielle Brill with Truist Securities.

Big congrats on these incredible results. So I have a question on response rates by background therapy. Since the majority of patients represented in the go analysis were receiving background standard of care. I'm curious if there were any discernible patterns or differences in response rates observed based on prior background therapy, whether that be steroids or IVIg. And then can you also comment on the median time to response? I know it's a small end, but curious if you were seeing responses concentrated around a certain time frame or if they were dispersed across the 13-week evaluation period?

Yes. So I'll be very open. I know the answers to all of your questions since obviously, we have patient-level data but there are several of which it's just not the right time to speak about publicly. And the reason for that, frankly, is just to maintain the integrity of our study, right? So in other words, this is a registrational study. We are at the beginnings or the beginning phase of recruitment. And the last thing we want to do is to influence physicians or patients in terms of their expectations in Part A because what we want to do is make sure that our Part A response rate is as rigorous as possible that these are true responders so that the ones on placebo will deteriorate and we have a successful Part B, right? So that's part of the reason why we've released limited information.

What I feel is fair to say is that, number one is that our response rates were not clustered. And you wouldn't expect them to be in a disease like this because CIDP patients are each one is kind of their own individual story. Fast forward 20, 30 years, we may find out that CIDP, the way we look at it today is 3 or 4 different diseases that have similar external physical symptoms. So this is why patients have very different courses and very different responses to therapy. And in that type of situation, you want to see exactly what we see, which is people have very different periods in terms of when they respond to something, some respond very well and some don't, right? And that's exactly what we've seen in our study.

In terms of different subgroups, all I will say is no surprises. Like the only surprise is what Marino mentioned earlier, what I've mentioned with caveats as well, which is that it seems like overall, the response rates are higher than what we anticipated, but the pattern of them is pretty much what we expected.

Does that answer your question Danielle.

Our next question comes from Ryan Deschner with Raymond James.

Congratulations on the results today. Real quick, given the substantial reduction in enrollment for CAPTIVATE, how much time do you think you could realistically shave off your time line to potential approval in CIDP? And what needs to happen logistically with regulators to remove that 600-milligram dose arm in CAPTIVATE?

Look, in terms of speed, clearly, we've been doing really well. And now the changes we're making to the trial will accelerate our ability to get to top line results. Again, we'll provide guidance on what that looks like later this year. I'll tell you what's on my mind is just a couple of years ago, riliprubart was probably about 3 years ahead of us to market.

Based on their delays, based on our acceleration to date, that difference is now in the 1- to 2-year frame. And so what I'm looking for is further updates from them, and then you'll get further updates from us later this year. And then we'll see if we've been able to minimize or nullify that first-to-market advantage they had at one point. That's what I'd like to see. And that's what I'm really focused on right now. On the second part of your question, I'll hand it to Sim.

Yes. We have pretty rapid mechanisms in most countries that we're going to leverage to cut the 600 arm off. So I don't feel like we're going to waste any patients recruiting to 600.

It's going to -- this is something that we suspected early on when we first started seeing patients coming to Part A. So team is ready to execute really quickly on this.

Our next question comes from Colleen Kusy with Baird.

Congrats on the data. Given the strength of data that you're seeing so far, is there any reason you'd want head-to-head data versus IVIg either for regulators or for commercial? Or would that be something you'd entertain maybe in a post-marketing setting?

Yes. Look, I'm eager to see the head-to-head data from -- especially from riliprubart. And of course, that will inform us because at this point, we believe anything that riliprubart could do, we probably could do or match for sure or do better. So once we see that data, then we can decide how we go about creating our own head-to-head data versus IVIg. And it may not be in the same form that they've done it because we don't need it for registration. It will be purely, as you said, commercial requirement or nice to have. So yes, it's something we definitely have in our mind. And I think the data we see from our competitors will inform that.

Our next question comes from Bill Maughan with Clear Street.

Congratulations. So to ask a little bit more on the timing of responses. If we assume that you are more potent than riliprubart, would we also potentially assume that you may see responses faster and not only just more frequently? And then on the other side of the time line, is there any thought that you may be leaving some responder rate points on the table by looking at week 13 endpoint versus looking a little bit further?

Yes. So, yes. I think in general, if a drug works and you're more potent, then you probably should see results a little bit quicker. But without knowing their data set and their specific points at which they responded, I have no way to accurately answer that question yet. It's possible, I don't know.

I just know that overall, we're really pleased with the responders that we're seeing. In terms of lengthening the study, it's a balance, right? Because there's cost involved, there was cost involved. There's the fear of [ dribble travels ] at the end who maybe aren't true responders. So again, my focus and the team's focus, yes, we want to see responders, but we also want to make 100% sure that we're doing everything we can to get true responders who should relapse once they're off of our drug.

And the fear of course is the longer and longer you go and you get a [ dribble travel ] at the end, was that a real responder or somebody who's just been in there long enough to feel better on their own. And so we cut it at 13 weeks. And then we saw the results that we saw, and then so we didn't really feel a need to extend it any further. And that's the best answer I have to give.

Yes. I think here's the bottom line. As Sim said earlier, extending Part A was an option if we weren't seeing pleasing results in the first 13 weeks. We didn't just see pleasing results that told us, okay, we have a go. We saw results that materially were better than our expectations. I just want to make that clear. It's not results that we say, okay, this is great and met our objectives.

This is clearly much better than we had hoped and expected based on precedent data with riliprubart. And so absolutely, 13 weeks was the right decision.

Our next question comes from Laura Chico with Wedbush.

This is Dennis on for Laura Chico. So how did the CAPTIVATE study modifications change your powering assumptions around Part B?

Yes, we basically have eliminated the 600 arm, and we increased the responder rate from 40% to 50%. So it resulted in a reduction in Part B from --...

Sorry, I think we went from [ 92 to 128 ] patients in Part B. We got rid of the 600 arm. And now it's actually stronger power to show a separation because 300 and 600 split the alpha before, and now we're not splitting the alpha. Does that answer your question?

We will take our last question from Jake Batchelder with William Blair.

This is Jake on for Myles Minter. I just wanted to confirm that you guys have regulatory alignment on a sufficiently sized exposure database now with this 128 patient downsizing.

Yes. I mean we didn't go back specifically to regulators to ask them if this number of patients in Part B is adequate, but we use our sort of common sense based on our conversations in other indications that we've just had such as MG, where we have far fewer patients overall that are going to be dosed.

And so we feel pretty comfortable that the overall exposure data, especially with sort of a 1-year Part B, 13 weeks ahead of that. So over a year in a registrational setting plus an extension beyond that. And then let's not forget that regulators do look at from a safety perspective, which is the question you're really asking, they do look at like doses in similar indications. And so we have 300-milligram data all the way from Phase II with people with 1-year extension will be tested again in Phase III, and we have the same doses and higher in MMN. So we feel like we have plenty of safety data.

Does that answer your question?

All right. Great. Thank you. So if I could just close, thank you, everybody, for attending the call today. And I just want to again highlight how proud I am, how overjoyed I am with the results we've seen so far and the Dianthus team's execution. So a big thank you to them.

The fact that we're making this early call and on top of that, raising the bar and changing our ratio from Part A to Part B because of the materially better, materially significantly better results we're seeing than expectations and the precedent set with this mechanism of action, it's just better than everything we had hoped at this point. And especially because we're seeing consistency in terms of the baseline characteristics with patients. We don't have more naive patients, for example, than riliprubart had as a percentage and the fact that we're seeing very consistent results across different geographies, different health care systems, different ways of treating CIDP in different countries.

It is really, really a great moment for Dianthus, and I'm especially excited for CIDP patients and what this drug could do for them. So with that, let me conclude again and thank you. And if anybody would like to -- any investors would like some time with the Dianthus team today, please reach out, and we'll do our best to schedule some time with you. Thank you.

Thank you for your participation. You may now disconnect.

[Audio Gap] Biotech Summit 2026. My name is Yatin Suneja. I'm joined here with my colleague, Delma Caiati. We will be moderating the next discussion with Dianthus Therapeutics. From the company, we have two executives here. We have Marino Garcia, the Chief Executive Officer. We also have Ryan Savitz, who is the Chief Financial Officer and also leading the charge on the business development front.

Marino, always good to have you. Thank you for your time. Why don't you make some opening comments, then Delma and I will moderate the discussion with you.

Sure. So thank you to Guggenheim, and you specifically, for hosting us here. And obviously, I'll be making some forward-looking statements. So I just want to refer everyone to our website and our SEC filings for all the appropriate risks around Dianthus.

So it's a very exciting time for the company right now. 2025 was a transformational year, where we had our first set of data in patients with a neuromuscular condition, myasthenia gravis, which I think most investors would agree was an upside best case scenario. We in-licensed 212 from Leads Bio in China, a potential best-in-class and product -- pipeline and a product that -- bifunctional fusion protein that targets BDCA2 on one side to reduce Type 1 interferon and BAFF/APRIL on the other side. And in vitro and in nonhuman primates, it looks like it may be more potent than Litifilimab, which is in Biogen's portfolio, and being studied in SLE on the Type 1 interferon reduction side on the PBC depletion side.

And then on the other, on the BAFF/APRIL, it looks like we have a deeper, longer depletion of IgG, IgA and IgM compared to povetacicept. So we now have two products in the clinic. And we entered -- or we start off 2026 with two major catalysts coming for Claseprubart, our lead program. It's an active C1S inhibitor, highly potent long half-life, as I mentioned, with very impressive MG data from our Phase II trial back in September.

And those two catalysts are -- we have our CIDP Phase III single study sBLA interim responder analysis for the first 40 patients that is coming up. We've guided to second quarter of this year, accelerated from the second half of this year just a few months, ago as recruitment is going very, very well there. And then MMN, our third indication, our Phase II top line results in the second half of this year.

And with 212, the next catalysts are in the first half of this year. We will have clarity on which 3 indications we're going to go after to maximize its pipeline or product potential. We'll announce those, as I said, first half of this year. And second half of this year, we will have top line results from our single ascending dose healthy volunteer study being conducted by a partner in China. And -- and then we'll have -- the second part of that SAD study is actually testing 3 of the doses that we're testing in the healthy volunteers in SLE patients, and that we will have results for in the first half of next year.

Got it. Very good. So let's just first focus on CIDP because there, you have a very near-term upcoming catalysts that investors are focused on. So for the CAPTIVATE study, what are -- how are you thinking about, number one, communication? What exactly you will communicate in this Part A? What is the benchmark? And what not is the benchmark? Like I think people investors understand that CAPTIVATE is a unique study different than the ADHERE study that VYVGART or argenx ran. So just frame that for us.

So we're very excited about this study in CIDP. I think first, I would just remind folks, riliprubart is an active C1s inhibitor in Sanofi's pipeline. They're in two Phase III studies for CIDP. One is a head-to-head study versus IVIg, a very bold, confident move to show at a minimum non-inferiority to IVIg and potentially superiority. And that's based on their really outstanding groundbreaking Phase II data where they saw in patients who are on IVIg and stable, or IVIg refractory standard of care stable -- or standard of care refractory. They saw when those patients were switched over within 7 days. So the next dose of IVIg instead replaced by this active C1S inhibitor, they saw something like half of the patients improve, do better than they were doing on IVIg. That's a very strong efficacy signal.

So what we're looking for in this interim responder with the first 40 patients in the open-label portion of our trial, the Part A of our single Phase III trial, is efficacy that looks similar, at least similar to riliprubart. Again, at the end of the day, when we go to market and riliprubart is potentially on the market as well, we want to be able to say that it's at least equal in efficacy because we are much more potent. And that means that at a minimum, we're going to have 1/4 less the injections that riliprubart doses.

So they're dosing 600 milligram, 4 milliliter a week. We dose 300-milligram 2 milliliter every 2 weeks. So at the end of the month, if it's an auto-injector that can take 2 milliliters, it'd be 8 shots for riliprubart, 2 for us. And that is a direct result of the fact that we are much more potent active C1S inhibitor and therefore, can give less drug to get above the IC90 or similar potentially efficacy. So we're looking in that Part A to see similar results to what riliprubart saw in their Phase II study. Anywhere around 40% to 50% or greater efficacy. And that means patients who are -- 40% to 50% of patients who see an additional improvement of 1 point on the INCAT score. Those are considered responders. And those are then the ones who get randomized into the blinded randomized control Part B, where it's essentially we put some of those responders on placebo, and some of those continue on drug, and it's up to 1 year to wait to see the placebo patients relapse and then the separation between active and placebo.

So we're very excited about what we could see here in the interim responder. What are we looking for? We're going to be very limited in terms of what data we can disclose. I'm telling you what we're looking for is to say this is at least equal to riliprubart in terms of efficacy because that, in the end of the day is what's required to go to market and compete effectively. What I'm going to be able to tell investors publicly, because it's an ongoing trial, is very limited.

So there's three things I'm telling folks to look for. One, are we keeping the dose in Part A the same? If we are, 300 milligrams every 2 weeks, that means it's working. It's working like we had hoped it would work. It's at least equal to riliprubart, if not better. The second part, in Part B in the blinded randomized portion of the trial, we have 3 arms. Placebo, 300 milligrams every 2 weeks, and then we have 600 milligrams, a higher dose. Did we get rid of the 600 milligrams? Or are we going to get rid of the 600-milligram arm? If we're doing that, again, it should be interpreted as we are seeing efficacy that really tells us we have a winner here from Part A, that we don't need that higher dose.

What does that mean? It's not just that we just made this trial cheaper, maybe faster, definitely faster, is that riliprubart and Sanofi, they keep delaying the results of their Phase III. They keep delaying their time to BLA. While we're accelerating our time lines. We're having the opposite experience with our trial. If I cut this -- if we cut this trial down by 1/3 and get faster, we may be able to neutralize what they -- at one point was a 3-year advantage to the market, down to something that could be insignificant. And that's huge in terms of the potential penetration and value for this program in CIDP.

And then the third thing I'm telling folks to look for is our recruitment numbers for Part A and Part B, the ratio. So right now, we are targeting 192 patients total on Part B. For that, we believe we need to recruit conservatively up to 480 patients in Part A. If you do the math, that's a 40% ratio. And again, as I mentioned, we're looking for at least a 40% to 50% responder rate in those first 40 patients that tell us that this is going to be at least equal to riliprubart. If that ratio, when we announce the interim responder analysis stays the same, again, it means we are seeing efficacy like we had hoped from the very beginning.

And that is -- those 3 points should give everybody confidence that we believe we have something that's at least equal in efficacy to riliprubart, potentially superior, so that we can very effectively compete when we get to market with riliprubart and CIDP.

One more point I'll make because you asked about the differences between our trial and ADHERE. We pretty much copied the ADHERE trial. This is a highly enriched trial, a very high probability of success, and they had an indication for all adults with CIDP, which is fantastic. So we replicated that, but there are some important differences.

One, we do allow refractory patients into our trial. FcRns don't allow refractory patients into their trial from IVIg. Why? Because FcRns are less effective than IVIg. So if you're refractory to IVIg, unlikely you're going to respond to FcRns. So we do allow them because the data from riliprubart is very clear, robust. Patients who are refractory to IVIg when put on active C1S inhibitor, 50% got better. That's a huge, huge benefit for those patients who have really run out of options in CIDP.

Secondly, in ADHERE, they took patients who are stable on standard of care IVIg, removed the IVIg, washed it out and only patients that relapsed were then allowed to go into Part A, the open-label portion. We don't do that. That's a relic of the past. Nobody is ever going to do trials like that anymore. We switched them within 7 days. Why? Because again, riliprubart's data very clearly showed you just have to switch right away. You don't have to wash out the IVIg and they saw great efficacy. So we're doing the same. And by the way, argenx with empasiprubart, they're doing the same, switch within 7 days. There's no need to wash them out and make them relapse.

And then finally, that 67% responder rate that argenx saw with empasiprubart in Part A, remember, that's after patients relapsed when taken off of IVIg. Patients were stable on IVIg taken off, relapsed and then only those put into Part A. And that means 2/3 of patients were able to get back to stable as they were on IVIg before. That means a full 1/3 didn't get back to where they were with IVIg.

When you take -- when you look at the riliprubart data for those stable patients on IVIg, they were switched right away. No relapse, and 50% did better than they were doing on IVIg. Those are very different numbers. So you can't compare 67% to 40%, 50%. It's a very different number. We're looking for superior efficacy, or we're looking for an enhanced efficacy signal over standard of care in IVIg, just like riliprubart saw in their Phase II.

Two quick questions, and I'll hand it over to Delma. So I think the biggest change I have noticed is at least for the CAPTIVATE study is the possibility of dropping the 600-milligram arm, right? That would make the trial more efficient, faster, whatever, however you -- what is underpinning that potential? And why?

800 milligrams every 2 weeks with us, we know gets above IC90 on the CH150mlo assay. It's really potent. We saw in MG that there was no dose response between 300 and 600. There's no benefit in that neuromuscular condition to be above IC95, for example. We now have cemdisiran data in MG that shows that at 75% inhibition, they still had a 2.3 improvement on the MG-ADL and therefore, had good efficacy.

So there is no evidence in neuromuscular conditions that you have to be that high level of inhibition. So I -- we really doubt 600 milligram is going to add any benefit. And we'll have more confidence in that, obviously, in CIDP once we see how patients are doing on the 300 milligrams every 2 weeks in CIDP. Riliprubart had really impressive data. I don't believe they're above the IC90 on the CH150mlo assay. I believe they're achieving that data with a lower level of inhibition than we are doing with 300 milligrams every 2 weeks.

So you don't need to.

Yes. Maybe turning to the MMN program now. So we can consider that indication is largely derisked by C2 inhibition and placebo from argenx. And the key point is how can you differentiate from that? What mechanistically? So is there any expectation that you can show higher efficacy than empa? And also in terms of safety, convenience...

Sure. So empasiprubart had really impressive data in Phase II with MMN. Their Phase III has a slightly different primary endpoint, it's grip strength. So we'll see the results of that. I believe they said in the fourth quarter of this year.

So at a minimum, we believe we should have similar efficacy to empasiprubart, and I'll tell you in a moment why. With the advantage of -- they're in IV every month. We're going to be a subcu self-administered auto-injector every 2 weeks. So that's a clear advantage for the patients. And we also believe we're going to have a safety advantage because they do block the classical pathway, which is where all the efficacy MM comes from, but they also block the lectin pathway. And blocking both those pathways, those are the two pathways that are needed to trigger and activate the complement system. The alternative pathway kicks in once one of those 2 pathways is activated and revs up the formation of MAC.

So if you are blocking both the classical and lectin pathway, I'm not sure how the complement system can react to the presence of encapsulated bacteria. So I think the FDA will probably put a box warning on it. The only complement inhibitor -- well we do have Enjaymo now, or sutimlimab that's been on market for 4 years and has no box warning, and that's a pure classical pathway inhibitor. So there's going to be at least, I think, a dosing and safety advantage.

On efficacy, we finally saw empasiprubart, or argenx published potency data in terms of how well they shut down the classical pathway. And so they did it with the Quidel MicroVue assay. So we said, okay, we've never done that assay, but let's go ahead and test ourselves versus empasiprubart with that assay that they published in. And they only published this IC50 as well. And when we run that test multiple times, we get similar data for them than what they published. Actually, it looks a little better in our hands. And at IC50, we're at least 6x more potent.

Now if you look at the curves on the slide, if you said, well, you need to be above IC90, was -- we didn't put those numbers on there because they never published it. So we said, okay, let's just -- like we're just showing what they published. But in our hands, they not experiment. At IC90, we're 30x more potent. So the difference between us and empasiprubart is more dramatic than it is versus riliprubart.

So the question then comes down to -- if you have that much more potency in shutting down the classical pathway, will that translate to more efficacy in MMN or CIDP? And we don't know. We know that with MG, 75% inhibition now looks like good enough. So that's why we're testing a once-a-month dose there. That and the fact that we saw really great data, promising data in our open-label study that tells us we don't -- at half the PK levels we achieved with every 2-week dosing, which is what we would get at every 4-week dosing, we're seeing really good responses from placebo patients going on to open label. So at a minimum, we expect similar to riliprubart and empasiprubart. Our experiments, our data when we complete the program will tell us whether higher levels of potency deliver higher efficacy.

Got it. And there you're testing both the 300 milligram and 600 milligram?

In our Phase II MMN study, we are testing 300 and 600. That's right.

Okay. And thinking ahead to the commercial perspective. How would -- what would be winning for you on a hypothetical scenario where both empa and Claseprubart work? So how do you see the competition in the market between the two products?

I mean MMN is a smaller market than CIDP and MG. But it's estimated to maybe about 10,000 patients in the U.S. But that's it. It's just us and empasiprubart. IVIg doesn't work really well there. The patients really, really need something to help them. And so if we have similar efficacy to empasiprubart, really by the time -- when we're approved, there's only going to be really two options for these patients of efficacious biologics.

There will be empasiprubart with an IV and a potential box warning. Let's assume similar efficacy to us. And then us with an auto-injector, we're using the same auto-injector Dupixent uses. It's by the company SHL. It's a 2-milliliter 5-second click done. You don't see the needle, very easy. You keep it in the fridge, you can travel with it for up to a couple of weeks at room temperature. Very, very easy for patients to self-administer. Very much like the GLP-1s, for example. And no box warning.

I think it's going to be pretty clear. I mean I don't see a physician talking to an MMN patient saying, okay, there's a complement class that work really well. Let's assume they're approved and work really well. There's one that's an IV, once a month, whatever, and then there's another auto-injector. They're going to have to mention the fact that one potentially doesn't have a box warning and is safer. Now that's if they end up with a box warning. Bottom line is we will have an advantage on 1, 2 or 3 of the efficacy, safety or convenience factors.

Makes sense.

And then the pricing, we'll see. It will be interesting to see where they price empasiprubart with MMN as a first indication. It is small in CIDP. And if you look at efgartigimod, that's double the price of MG. And that means it could be pretty high 6-digit number per year in CDP and MMN. So that could be another place where we might have a bit of an advantage.

Okay. And maybe turning to the MG program in the interest of time. So did you have already the end of Phase II meeting with the FDA? What's the status of the program? When will you start the Phase III trial?

Yes. We had a very good meeting. So now we're just waiting for the written feedback. So as soon as we have everything in black and white, like we've done always before, then we pretty much, then, disclose the full details of the program. But I'm very, very happy with the job the team did and the meeting we have with the FDA.

And in Phase II, you had very robust data on QMG, MG-ADL. And then there was an interesting post-hoc analysis where you saw that in patients with higher QMG, or more severe patients, you had a better efficacy. How are you integrating those findings into the Phase III trial?

Yes. I mean that Phase II data, as I said, I think most investors would believe that the data was best case in terms of the efficacy. But if you look at it, the placebo response was high. It was closer to 3 on the MG-ADL response than 2, which we've seen traditionally with complement inhibitors.

So we looked into that. And what we noticed that is, obviously, we didn't have a QMG screening criteria. That's a very long process, physician administered take 2 hours. We were a young company during our first trial. We want to make it really easy to recruit into our trial to make sure we hit our time lines. But we did a post-hoc analysis and we said, well, what if we had a QMG screening criteria.

Zilucoplan, the last C5 approved in MG had 12 or higher as well as MG-ADL6 or higher. We did 10. Like, let's say, just a little lower, make it a little easier to recruit in that trial. What if we had a 10 QMG as a minimum to recruit into the trial as well as the MG-ADL screening criteria. And we saw that the placebo then was more around 2, like traditional C5s. And all of a sudden, the difference for 300 milligrams between active and placebo was a 3 point on the MG-ADL. That's -- I mean, that's not been seen in complement or sharing in this market.

So we believe by having a QMG screening criteria as well as the MG-ADL screen criteria we'll be able to better control for placebo. We've learned a lot from this Phase II trial and we'll implement that in Phase III. So I believe now our TPP doesn't say equal efficacy to C5. It says equal or superior. That's what I expect. On safety, the same, no box warning.

The -- on convenience, we also had a little mini experiment designed into our Phase II, where we took placebo patients. And when we switched them to open label, Claseprubart, we didn't give them a loading dose. And that was done on purpose to give them one shot every 2 weeks and watch the PK levels accumulate slowly and see what happens to their MG-ADL and QMG. And we saw that just after 2 doses where they achieved a PK level on average that's half of what you achieved dosing every 2 weeks with an 8-week half-life linear PK, that means basically the same PK level we would achieve if we dosed every 4 weeks. These patients had another big drop in the MG-ADL on top of the already high response rate they had on placebo.

That with -- combined the cemdisiran data, which shows that only 75% inhibition got you pretty good robust efficacy. There's no reason for us to not test every 4 weeks. And I am fully confident that every 4 weeks may be the dose we end up with on the market, which makes it even -- it's taking a strength we already have and pushing it even further. So imagine a complement inhibitor with no box warning, every other complement inhibitor in MG is going to be -- have a box warning. They're all C5s, potentially better efficacy, and a once-a-month auto-injector. I mean that to me is a great game changer, and I don't see how this doesn't become a first-line treatment for MG with many, many patients.

Got it. And maybe one last question on safety. So the risk of lupus accounts there in conversations with investors like -- and there was recently a report from Enzyme on the first database of a case of lupus observed. What do we know about that case? How reliable is that database? How does the FDA analyze the data? And when do they act on those data?

Yes. Look, the FAERS database, anybody can go on there and report anything. So sutimlimab, after 4 years in the market, has a consumer put in a report. It wasn't a health care professional. It says it was off-label. It was -- the dose was not what they recommend on the label either. And then it lists a whole bunch of conditions. And in there, they mentioned SLE.

You don't know if they're talking about what they were trying to treat because it was off-label or it was a side effect, doesn't say anything. And there's really no control. There's no way to confirm any of this. I would just point out to speak to how unreliable the FAERS database is. VYVGART, I don't think anybody has any concern that it could trigger DIL, or drug-induced lupus, which is a very common side effect for the anti-TNFs. You can see it on their label like Humira or ACE, ARBs and blood pressure meds. I don't think anybody believes that's a potential risk with VYVGART, but they have 10 cases reported that mentioned SLE. Soliris, a C5, I don't think people believe that, that has any kind of DIL risk. And yet they have over 100 cases reported. So it's just one of those things where we have no information. There's no control over what people put on there. And it's, like I said, not even a health care professional.

And yes, so all I can say is for sutimlimab, riliprubart, us and all clinical programs with patients on drug for years, there's been absolutely no cases of a patient reporting a rash that the physician says, oh, this is drug-induced lupus. And by the way, if that ever happened, we'll know it will be very rare. And all you have to do is stop the drug and the rash and the symptoms go away. This is not triggering lupus for life. This is DIL, a very common side effect. It's on the label for every single anti-TNF, ACE, ARB, et cetera.

Marino, could we spend the next 2, 3 minutes just on the commercial side? I think now you are talking about 100,000 ACHR positive MG patients. That number seems to have almost doubled. Where you are? Where do you see the peak potential for your product, how you are sort of modeling it internally?

Yes. So we haven't gone into forecast and numbers yet. But look, let's assume it's about 100,000 ACHR patients in the U.S. alone, by the way, just talking about the U.S. market. Not Europe, not Japan, not globally. Right now, biologics, less than 15% of patients are on biologics, FcRns or C5s. That, to me, tells me that this market is significantly underpenetrated. This market is maybe a $5 billion market in the U.S. alone. It should be a $20 billion, $25 billion market.

So when I look at the potential for something like -- complement and FcRns are going to be two mechanism of actions that are going to be first line, each other's first switch for many years to come. A very conservative market share assumption for us. Let's say, 5% to 10% share, is that fair? We're going to be the only complement inhibitor with no box warning and an auto-injector, and every 2 or 4 weeks, I think it might be every 4 weeks.

If you just assume a 5% to 10% market share of the MG market, and we're at $400,000 a year, that's right there, a $2 billion to $4 billion drug in MG alone. If we are the standard of care and more efficacious in IVIg than in CIDP, again, and maybe potentially double the price, if that's once every 2 weeks versus once every 4 weeks in MG. So it's twice as many injections for us per year, but still an advantage over empasiprubart and riliprubart.

Is 5% to 10% market potential there fair? Again, that's maybe $700,000, $800,000 a year. I mean, you can do the math. It's billions in CIDP. And in MMN, which is the smallest of the market, again, 10,000 patients that potentially could be on biologics. Say half of them go on biologics. And we split it between us and empasiprubart. Give them the market share leadership, only 2,000 patients for us. If we're somewhere around $700,000, $800,000 a year there, that's, again, another $1.5 billion on top. So there's no -- even very conservative assumptions, there's no reason why we can't see see Claseprubart peak sales getting above $5 billion over the long run.

Very good. Final question. Ryan, how is the financial health, the burn rate and the capital requirements in the future?

Sure. So we ended the year with $514 million of cash, which takes us into 2028. So meaningfully through the milestones we highlighted for Claseprubart, this year as it relates to the CIDP interim responder and the Phase II MMN data in the second half of this year, and also allows us to read out the milestones for DNTH212 with the Phase I healthy volunteer SAD data this year and then some SLE data next year as well.

Perfect. Thank you, gentlemen. Thank you.

Thank you.

Good afternoon, everyone. I hope you're enjoying the first day of the conference and all the festivities. My name is Alex Buckley. I'm with the Healthcare Investment Banking Group, and it's my pleasure to introduce Dianthus Therapeutics, and Marino Garcia, CEO. We'll have some time at the end for Q&A. If you could just raise your hand, and there will be a mic that goes around.

With that, Marino.

Thank you, Alex, and thank you to JPMorgan for the opportunity to present today an update on behalf of all the employees at Dianthus Therapeutics.

Just a reminder, I will be making forward-looking statements, so I refer you please to our website and our SEC filings for all the appropriate investment risks.

At Dianthus, we are developing two clinical-stage autoimmune therapeutics with best-in-class pipeline and product potential, both of which are targeting patient-friendly infrequent subcutaneous self-administration.

The first of these programs is claseprubart. It's a highly potent long half-life, 8-week half-life classical pathway inhibitor that targets activated C1s. It is a validated pipeline and a product potential with positive Phase II in MG that we disclosed back in September and clinical proof of concept for classical pathway inhibition in CIDP and MMN. We have clinical and in vitro head-to-head data that support the potential for a more effective and convenient biologic with no box warning or REMS program. And again, here, we are targeting the convenience of a single, self-administered subcutaneous 300-milligram 2-milliliter auto-injector dosed every two or four weeks.

Our second program, DNTH212, which has now started its Phase I clinical trial is a bifunctional BDCA2 and BAFF/APRIL inhibitor targeting two validated pathways, the innate and adaptive immune system. The BDCA2, we have in vitro data that very clearly shows superior pDC depletion versus litifilimab. And the BAFF/APRIL side, we have NHP data that shows deeper, longer IgG, IgA and IgM reductions versus povetacicept. And the idea here is to take these two best-in-class parts of this molecule, combine them into one to go after diseases where we know that type 1 interferon reduction as well as B-cell depletion could lead to superior efficacy over any one monotherapy approach. And again, here, we're targeting the convenience of a subcu self-administered dose every four weeks or less frequently.

So just focusing first on claseprubart. We're very excited about how claseprubart is pursuing the -- what we call the power of consistent control with one click and the unique efficacy and safety benefits that come by being a potent upstream inhibitor, a classical pathway inhibitor that leaves a lectin and alternative pathways intact. That could provide not just the efficacy of being able to prevent the membrane attack complex, but also the formation of C3a and C3b. Two very toxic pro-inflammatory split products that are created between the classical pathway and where C5 intervene in the complement cascade, while leaving the lectin alternative pathways intact to be able to fight against the risk of encapsulated bacteria. And of course, the convenience with having a long half-life and being a potent antibody of being able to dose low volume, 300 milligram, 2 milliliters every two to four weeks.

And the application that this has to a very large market in the neuromuscular space. In the United States alone, we're talking about 100,000 patients in the MG space that are AChR positive, north of 40,000 that are CIDP and north of 10,000 MMN. Together in the U.S. alone, we're talking about accessing over 150,000 patients with claseprubart.

So just focusing first for a moment on the opportunity to be a best-in-class first-line biologic in myasthenia gravis. In September, we disclosed very impressive efficacy data with 300 milligram, 2 milliliters of claseprubart in MG. Across the 5 different efficacy measures, we saw very robust, very rapid, clinically meaningful and statistically significant efficacy with 300 milligrams every two weeks. And we also said that if we did not see a dose difference between 300 milligram, 2 milliliters, and 600 milligram in this trial, that very likely we would take 300 milligrams, 2 milliliters every two weeks forward into Phase III, but also test a once-a-month dose.

Interestingly, to support this decision, at AANEM in October, subsequent to the release of the data, we presented this open-label extension data, where essentially we took patients who were on placebo for the first 13 weeks, where we saw robust response on placebo on the MG-ADL and QMG. And then we put patients into the open label on claseprubart. And we saw that without a loading dose after just two subcu shots at PK levels somewhere between 50 and 65 micrograms per ml, which essentially replicates the steady state of claseprubart if we were to dose it every four weeks.

We saw that patients on top of the already robust response they had in the randomized placebo-controlled first 13 weeks, they had another significant drop of 2.5 points on the MG-ADL and 3.2 after just two doses on the QMG after just two doses. And again, at PK levels that are half of what we see when we dose at every two weeks. In other words, the exact same PK levels we would get if we dosed every 4 weeks. So this gives us even more confidence that we should see in our Phase III efficacy at four weeks that would be equivalent to every two weeks.

I mentioned we had a very robust response on placebo in our randomized controlled portion of that trial. And as you can see on the left of this slide, the placebo responders were about 2.8 on the MG-ADL. That's closer to 3. And traditionally, we've seen with C5, as you can see on the right with zilucoplan that the placebo response was closer to a 2-point improvement on the MG-ADL.

So we asked ourselves what could that be? And what we noticed is in the zilucoplan Phase III, they did have a QMG screening criteria, not just an MG-ADL screening criteria like we had in our Phase II. So we asked ourselves, what if we had a QMG screening criteria in our Phase II. And you can see in the middle there that with minimal loss of number of patients, our -- the placebo response would have been closer to a 2 just like with zilucoplan. And the difference for claseprubart, 300-milligram 2 milliliters every two weeks versus placebo would approach a 3.0. point difference versus placebo on the MG-ADL. That is a number not seen before with a complement inhibitor. So this gives us the confidence that if we just screen out for high placebo responders with a QMG screening criteria on top of MG-ADL, we could really see this antibody shine and show what it can do.

And the reason we believe we could see better efficacy with claseprubart over C5s or terminal inhibitors is, as I mentioned earlier, it's very simple. An upstream inhibitor prevent C3a and C3b deposition, C5s act too late to prevent this. These are pro-inflammatory toxins that are being created as part of the complement cascade and deposited at the neuromuscular junction. So if you can imagine a patient who's on C5, they're preventing the formation of MAC, which is the primary driver of disease or dysfunction in MG. But they still have C3a and C3b causing inflammation at the neuromuscular junction. With an upstream inhibitor like claseprubart, we would be able to also prevent this on top of preventing the MAC. And for that reason, we believe we could potentially see superior efficacy or enhanced efficacy over C5s in MG.

So, our Phase III trial, we're now in dialogue with the FDA, and soon, we will provide an update as soon as we have confirmation and in writing that we agree on what the Phase III will look like. We're looking at doing placebo versus claseprubart once every two weeks and claseprubart every four weeks. And as soon as we have that in writing, we'll announce the start of the trial and provide further guidance on it.

But one point I'd like to finish on with MG is we have a new enhanced target product profile. In the past, we said we're looking for similar efficacy to C5s. We are now saying similar or better for superior efficacy.

On safety, consistent with what we said before, no safety signals that would justify box warning or REMS program of any kind, again, creating that very strong differentiation versus other complement inhibitors. And finally, because of what we've seen in our Phase II and the open-label extension, we're looking at potentially not just having every two-week dosing, but possibly taking every four-week dosing to market with this product, which would really make it the most -- absolutely by far the most convenient and patient-friendly biologic in MG.

Now moving on to the opportunity we have here to completely change the treatment paradigm in CIDP with claseprubart. CIDP is a market that offers substantial growth opportunity for claseprubart given the very high unmet need and the drawbacks or limitations of the current standard of care. IVIg works for quite a few patients, but it is very poorly tolerated and is very difficult and a big burden on dosing administration on patients. FcRns are now available, and that's great. It's a more patient-friendly version of IVIg, but it doesn't work as well as IVIg. It's less effective than IVIg. What this market needs is something that's equal or better on efficacy than IVIg, safer, better tolerated and certainly a lot easier to dose and administer for patients.

What's exciting here is there's very strong proof of concept with riliprubart with their Phase II data, which they published a couple of years ago. And this was a bit of a game changer for Dianthus.

What we saw is in their open-label Phase II data, they took all comers, patients who were refractory to IVIg. These are patients that FcRns will never study. They don't allow refractory patients into their trials, again, because FcRns are less effective than IVIg. But riliprubart allowed patients who are refractory to IVIg, stable on IVIg and treatment naive. And they switched them immediately to riliprubart, the active C1s inhibitor. And they saw really impressive efficacy signals.

If you look at the first group, the standard of care treated patients, these are patients who are stable and doing fine in IVIg, switched and 52% did even better than how they were doing on IVIg. Again, this is switched within seven days. Patients who were refractory to IVIg. IVIg did not work for those patients, 50% when switched to active C1s inhibition got better. Again, somehow active C1 inhibition, classical pathway inhibition extracting better efficacy than what IVIg could deliver for a large number of patients with CIDP.

I would remind you that the dose for riliprubart in this trial is 600 milligrams, 4 milliliters every week. That's also the dose we're taking into Phase III. So in other words, 4x more of a dose than we are. We're 300 milligrams, 2 milliliters every two weeks. So if there were an autoinjector, they would be two shots every week, we're one shot every two weeks.

What gives us the confidence that, that lower dose can deliver at least similar efficacy to what riliprubart saw, if not better. And what we did is we conducted six head-to-head in vitro experiments versus riliprubart. And I let you choose which one you want to focus on. But across the board, it's clear we are orders of magnitude more potent than riliprubart. And that's what gives us the confidence that we should be at least equal efficacy, if not superior to riliprubart in CIDP.

So we have our Phase III trial ongoing. And in the fall, we saw that riliprubart or Sanofi were delaying the top line results for their Phase III programs in the CIDP. But frankly, for us, it was the opposite. We actually accelerated. We had planned for our interim responder for our first 40 patients from Part A to read out in the second half of this year. But this fall, we saw that recruitment really accelerated, especially after we presented our MG, our MG Phase II results to our CIDP investigators.

Anecdotally, they told us that the results were really impressive. The safety really reassured them. And we saw basically recruitment like a hockey stick, just really accelerate this fall. So we've now moved up our interim responder analysis from second half of this year to the second quarter this year, and I can confirm today that we are well on track to deliver our interim responder analysis early in the second quarter of this year.

And one thing I would just make clear about what this trial -- how different it is from ADHERE because you'll notice for those of you who follow the space, it looks very similar. We have a Part A open label and then the randomized blinded portion Part B and only patients who respond in Part A are randomized into Part B. And that looks very much like ADHERE, but there's some very important differences that make any cross-trial comparisons challenging.

The first one, in terms of patient group, we allow patients who are refractory to IVIg or standard of care into our trial. Again, no FcRns allow that. Why? Because FcRns don't work as well as IVIg. If IVIg did not work for CIDP patient, very unlikely an FcRn will work. We allow them into the trial because we saw really impressive data with riliprubart.

Secondly, ADHERE took patients who are in IVIg, took -- remove the IVIg and then waited to see if they relapsed. And only those that relapsed were then allowed to go into Part A. We don't do that. We switch patients within 7 days. The next dose of IVIg is replaced with an active C1S inhibitor. It's replaced with claseprubart. So there's no making patients relapse. And I can tell you right now, moving forward, there are no CIDP trials are going to be doing that again. That's a relic of the past. Investigators hate it, and they will not recruit patients into trials if you are going to force them to have to relapse, make the patients relapse before they can go into a trial.

And third, related to that second point, we are looking for somewhere around 40% to 50% response rates in Part A to tell us that we have the right dose with 300 milligrams, 2 milliliters in the open-label Part A. But that is not a number you can compare to the 67% response rates that efgartigimod saw in their Part A. Why? Because again, they took patients who were on standard of care stable, no refractory, took the IVIg off, made them relapse and only those that relapsed then were allowed to go into Part A. So that 67% is essentially saying that only 2/3 of patients that relapsed were able to get back to baseline. That means 1/3 of patients were not able to get back to how they were doing on IVIg before the IVIg was removed.

In our trial, we take patients who are in IVIg standard -- doing well, stable or refractory. We switch them within seven days. So when we're talking about seeing 40% to 50% responder rates before we allow them to go into Part B, that's above and beyond what IVIg was delivering for those patients. So very different, a 67% from patients who had relapsed, only 2/3, meaning they got back to baseline versus us, we're looking for 40% to 50% responder rates above and beyond how IVIg was doing for those patients. So that's just on CIDP. We're very excited about getting to that announcement in the second quarter.

And then the third indication, the opportunity for a best-in-class biologic in multifocal motor neuropathy. This in absolute numbers is the smallest of the three indications this indications, but I can tell you, it is a blockbuster opportunity because there's no competition. The FcRns don't work here. IVIg is used, but it's very ineffective. It doesn't work very well here. It certainly doesn't work as well as it does in CIDP. There's essentially only one other biologic being studied in MMN, and that's empasiprubart. So it's essentially us and the C2 inhibitor from Argenx. That's it. And what this market is looking for is an effective treatment that is considered safe and well tolerated and easy to use, preferably a self-administered auto-injector. And that's what we offer with claseprubart.

With empasiprubart, they had really impressive Phase II data they published a few years ago, and they very clearly state the efficacy that they saw and they see is purely from the inhibition of the classical pathway that the fact that they block the lectin pathway provides no additional benefit for these patients.

So they finally published potency data for empasiprubart. And what we saw is they used the Quidel MicroVue CH50. And they clearly show the CH50 numbers there for classical pathway inhibition as well as for lectin pathway inhibition. So, we said, fine, now let's use that exact same assay, replicate empasiprubart and do a head-to-head in vitro experiment and see how do we behave compared to empasiprubart. And we saw that at the CH50, we were able to get very similar numbers than they did in their experiment. Actually, it looks a little better in our hands. So we did them a bit of a favor there.

But -- we are 6x more potent at the CH50. If you look at the IC90, we didn't publish this because they never published their IC90. But there, the difference becomes even more dramatic. It's more like 30x more potent than they are. So this should provide comfort that whatever efficacy empasiprubart has seen in MMN, we should see at least similar, if not better efficacy because we're a much more potent classical pathway inhibitor than empasiprubart.

So, in summary, with MMN, we know it's an IgM-driven disease and it's classical pathway driven. We now have data that shows we are a much more potent classical pathway inhibitor. We know they block the lectin pathway. We don't touch the lectin pathway and the lectin pathway is important in order to fight against the risks of encapsulated bacteria, things like meningitis. So it's very likely they would get a box warning. We will not have a box warning, that precedent is already set with sutimlimab approved on the market today. And finally, it is an IV given every four weeks.

We're aiming for a subcu auto-injector self-administered every two weeks. So that's it. That's the market competition. It doesn't take many patients if we're priced somewhere north of $400,000, $500,000 a year in MMN to have a blockbuster in our hands in this market because there's just no other competition except us and the C2 inhibitor from Argenx. And so we have our Phase II ongoing, testing our target dose of 300 milligrams every two weeks plus our high dose 600 milligrams, and we should have the top line results for this Phase II in the second half of this year.

And now moving to our very exciting second clinical stage program, and this is DNTH212. Very excited about this one. It's a bispecific fusion protein that, on the one hand, inhibits BDCA2, so reduces type 1 interferon by depleting pDCs. And as I mentioned earlier, we have in vitro data in our presentation that shows very clearly that we have superior pDC depletion versus litifilimab, which is being studied right now with Biogen in SLE. And on the other hand, we have the BAFF/APRIL piece. And there, again, we've shown in nonhuman primates that we have a deeper, longer reduction on IgG, IgA and IgM levels compared to povetacicept. And the idea here is to take these two best-in-class. That's not me. So it's to take these two best-in-class pieces, put them into one antibody and go after diseases where we know the innate and adaptive immune system are driving the dysfunction.

So, to be clear, despite the fact that we have a superior BAFF/APRIL potentially, we're not going after IgAN because there's no benefit to reducing type 1 interferon in IgAN. We're going to look at going after diseases, maybe SLE, maybe dermatomyositis, maybe Sjögren's. We have a list of indications on our presentation, and we'll provide an update on which ones we're prioritizing in the first half of this year.

And what is our target product profile? What are we trying to do here? We are trying to bring about enhanced or superior efficacy in diseases where we know the innate and adaptive immune systems are at play than any one monoclonal monotherapy approach with no new safety signals from what we already know about litifilimab, for example, in the behavioral class. And finally, with the convenience of a subcu self-administered shot every four weeks or less frequently, potentially every eight weeks. So right now, as I mentioned, we're in Phase I. And in the near future, we'll announce our prioritized indications. And in the second half of this year, we should have results from our Phase I healthy volunteer data. And sometime next year, in Part B of our Phase I, we'll be having data in SLE patients.

So with claseprubart, for 2026, we're looking to start the Phase III as soon as possible with three arms: placebo, one shot every two weeks, one shot every four weeks. CIDP, our interim responder analysis announcement coming in the second quarter of this year. and MMN, our top line results for our Phase II before the end of this year. And our latest update this morning, we have about $514 million of cash, which is -- takes us well into 2028 in terms of our runway. And with that, I think we can open up to questions now.

Super. Yes. Thank you, Marino. Obviously, a lot of progress this year and a very exciting set for 2026. So I'll open to questions from the room. Otherwise, there are some I have here.

Is this working? Yes. So Argenx is running a combo with efgartigimod and their anti-C2 antibody. Obviously, it's early with 212, but is that at least a thought about down the road combining the two mechanisms? Or is it still too early to think that far down the line?

Yes. I think it's too early. Sorry, can you hear me? I think it's too early to say. I mean that's an interesting experiment to run, but I'm not sure what the practical use of that is going to be. If you have an FcRn at about $400,000 a year, C2 that is targeting CIDP and MMN, which would probably take -- probably can probably charge higher than what you can in MG. I mean we could be looking at over $1 million of annual cost for two therapies in those patients. So interesting experiment, not sure you can do with that. A bispecific will be really interesting in the MG space for sure.

What are your plans in terms of moving manufacturing of claseprubart outside of China?

We have -- WuXi is our partner right now, and they're just fantastic. They're just really, really great partner. And I know many companies use them and would say the same. We are obviously looking that by the time we get to commercial that we should have a backup secondary supplier, one preferably based out of the United States, for example. So that's something we're very actively working on right now.

And is there anything that you find that investors miss about the story? Is there anything that -- or maybe don't fully appreciate?

One I would say is that this is a very different trial to ADHERE. They look the same. But as I mentioned, we are not making patients relapse. So when we say we're looking for 40%, 50% responder rates to replicate what riliprubart saw in their Phase II, that's when you switch patients immediately from IVIg or standard of care. So that 40% to 50% is above and beyond the responder rates IVIg was able to extract in CIDP versus the 67% that efgartigimod saw, that meant only 2/3 of patients that were forced to relapse were able to get back to where they were before when they were on IVIg, meaning 1/3 were never even able to get back to baseline. I mean, again, that's very different numbers.

This is why I think there are two companies right now, Sanofi and Argenx, who believe complement inhibition could be superior to IVIg. They're doing head-to-head trials. You do not do a head-to-head trial versus a standard of care in any disease unless you think you're going to win. And what I would say, and I say this to investors often, don't listen to me, don't listen to what any other CEO tells you. Look at behavior, not words, look at actions. Argenx has two therapies in CIDP. One is on the market today and would love to be able to say it's equal or better than IVIg in order to really accelerate adoption and get those revenues really, really going.

And the other one is a complement inhibitor in development. Only one of those two therapies is being taken forward into a head-to-head trial versus IVIg. And it's not the FcRn. No FcRn is going to study refractory patients. No FcRn is going to do a head-to-head versus IVIg because they won't win. Argenx and Sanofi are taking a very courageous move and doing a head-to-head trial versus IVIg. They're looking for non-inferiority at a minimum, which would be a win, but I think they're also expecting superiority. And if they show noninferiority, fantastic. You're as good as IVIg, but better tolerated and much easier to administer. But if you show superiority, it's game over for IVIg. And so I think that speaks volumes. And that is all based on the very impressive data riliprubart presented from their Phase II. So I think that's one thing.

The other thing is MMN sometimes gets overshadowed by the larger MG and CIDP market opportunities. But let's look at that for just a very quick back of the envelope. If it's 10,000 to 15,000 patients in the U.S., let's say, half of those would be eligible for biologics. So 5,000 to 7,500. It's only us and empasiprubart. What share would you give us of that 5,000 to 7,000 patients, let's say, 20% 30%, give the rest to Argenx, that's fine. If you just get 20% to 30% of those patients, you're talking about easily at $500,000 a year, you're easily a $1 billion blockbuster in MMN alone. That's it. And it's purely driven from the fact that, yes, it's a smaller market, but it's one where you just get a much higher share. And really, the competition is us and a complement inhibitor that blocks lectin likely has a box warning and is an IV. And we're 6x more potent classical pathway inhibitor. So there's a potential we might have better efficacy in MMN. I don't know that. Until we do the experiment, we're not sure for equal or better efficacy.

So MMN is one where I think once we get past the interim responder analysis in the second quarter, there are going to be two companies talking about MMN alone, us, but more importantly, Argenx. And I hope that together, we'll be able to really raise the profile for MMN and what a great opportunity that is for complement inhibition.

If there's nothing else from the room, then I'll Marino go. And thank you very much for attending.

Thank you.

Good morning, and welcome to the Dianthus Therapeutics Conference Call. My name is Michelle, and I'll be the operator for today's call. A slide presentation to accompany this call is available on the Investors section of the Dianthus Therapeutics website. Following the company's prepared remarks, we will move to Q&A session. Please note that today's call is being recorded.

I would now like to turn the call over to Marino Garcia, CEO of Dianthus Therapeutics. You may begin.

Thank you, Michelle. Good morning, everyone, and thank you for joining us today. Earlier this morning, we issued a press release with positive top line results from our Phase II MaGic Trial evaluating Claseprubart in generalized myasthenia gravis, and we're very excited to share more details about these results with you today on this call.

The impressive results we are presenting today are a reflection of the Dianthus team's commitment and passion. And I'd like to just take a moment to thank the team for their hard work in delivering a very well-executed and timely clinical trial. I'm very proud and grateful to be part of this team.

Next slide, please. Just a note before I begin the presentation, we will be making forward-looking statements. So I would refer you, please, to our SEC filings for more information. Next slide, please. I'm joined today by Dr. Sim Randhawa, our Chief Medical Officer; Ryan Savitz, our Chief Financial Officer and Chief Business Officer; and John King, our Chief Commercial Officer. I will begin with a few introductory remarks about the best-in-class potential we see for Claseprubart in myasthenia gravis, the first of our 3 neuromuscular indications we're pursuing. Next, Sim will review our Phase II data in detail. And finally, I'll summarize and discuss next steps and upcoming milestones. And then we will open up the line for questions.

Next slide. At Dianthus, we're building an exciting autoimmune company by rapidly advancing Claseprubart, a next-generation complement inhibitor with a best-in-class potential to treat multiple classical pathway-driven diseases. Claseprubart is a very potent investigational monoclonal antibody with a long half-life that is designed to selectively inhibit the active C1s protein and therefore, only inhibit the classical pathway of the complement system, leaving the lectin and alternative pathways intact to maintain the complement system's immune function. This unique combination of benefits means we could potentially have a very effective low-volume antibody with a lower risk of infections that can be delivered in a convenient, infrequent, self-administered auto-injector for patients suffering from various classical pathway diseases.

Claseprubart is a pipeline in a product with the potential to be a first-line biologic across different neuromuscular conditions such as MG, CIDP and MMN. And the results of our first trial in MG bolsters our confidence in cllosipravart as a potential game changer for patients in the MG market and in the successful execution of our ongoing CIDP and MMN clinical programs.

Next slide. Why did we choose MG as our first indication? The U.S. MG market is the largest of the 3 neuromuscular indications we're pursuing, with more than 100,000 patients that are AChR+ patients that can benefit from effective biologics. The U.S. is a $3.5 billion market and growing with only 2 classes of biologics competing for first-line use. The potential for significant growth is obvious as the C5 inhibitors and FcRns have only penetrated approximately 10% of these patients despite having been available for patients for many years.

And why is that? The reason we believe the market is so underdeveloped is that the current treatments have significant drawbacks and the market still has significant unmet medical needs. And this is where we see the substantial opportunity for Claseprubart to address these patient unmet needs as a potent, less burdensome and easier-to-use biologic. This best-in-class potential should be able to grow the market by reaching more MG patients that would otherwise delay the use of more burdensome biologics.

Next slide, please. In the MaGic Trial, our goal was simple: to evaluate 3 ways that Claseprubart could potentially address the unmet needs of these patients. First, on efficacy to be at least comparable to approved C5 complement inhibitors with a continuous effective symptom control and a 1.6 to 2.1 point improvement on MG-ADL versus placebo. Secondly, have a clean safety profile comparable to the FDA-approved first-generation C1s inhibitor ENJAYMO with a lower risk of infections and therefore, no FDA box warning or REMS.

And finally, a patient-friendly convenience comparable to DUPIXENT, the $14 billion blockbuster with the potential to have one-click delivery by a self-administered subcutaneous auto-injector just once every 2 weeks. We believe that achieving this TPP, this target product profile would be a significant advance for patients suffering from MG and would position Claseprubart as a potential first-line best-in-class biologic treatment. So how did we do with our first trial, the MaGic Trial against this target product profile.

Next slide, please. Today, I'm beyond pleased to say that the Phase II data supports our differentiated best-in-class target product profile for each of the 3 goals we set for the MaGic Trial and more. First, Claseprubart demonstrated impressive results with rapid, sustained and statistically significant symptom improvement across multiple efficacy measures, including the MG-ADL, the QMG and the MSC. These results support the potential for Claseprubart to be a best-in-class complement inhibitor, especially when you compare the results to the #1 blockbuster complement inhibitor, ULTOMIRIS.

Secondly, on safety, Claseprubart was generally well tolerated with a clinical profile similar to placebo. We saw no related serious infections and no symptoms of autoimmune activation. These results support the goal of not having a box warning or REMS program due to serious infections. And finally, the 300-milligram every 2-week dose, the results were consistently robust, statistically significant and clinically meaningful across all the measures we will share with you today. Both doses of 300 and 600 milligrams showed comparable safety and efficacy data with no statistical difference between them. Because we saw similar results across all efficacy measures between the 2 doses, we plan to advance the 300-milligram every 2-week dose into Phase III. Our low volume 2 milliliter supports our plan to deliver this in an SHL Molly autoinjector for self-administration, the same auto-injector DUPIXENT uses. Now I know you're all eager to get to the details of the results, so let me now hand the presentation over to our Chief Medical Officer, Dr. Randhawa.

Please turn to the next slide.

Thank you, Marino. It is my pleasure to present this data, which shows for the first time positive efficacy results for an active C1s inhibitor in a randomized controlled trial in a neuromuscular disorder. And I would like to thank the investigators and site staff who brought this data to us. The data story is quite simple. Across all commonly assessed efficacy metrics in MG clinical trials, both treatment arms had impressive treatment effects versus placebo with a low-dose 300-milligram Q2-week arm hitting statistical significance across the board.

We ran a typical MG study, enrolling patients with an MG-ADL of 6 or greater on at least one small molecule immunosuppressant and randomized them into placebo or 2 treatment arms, where we added Claseprubart, 300 or 600 milligrams subcu Q2 weeks. The randomized control period was 13 weeks, followed by a 52-week extension. As a reminder, our prespecified threshold for significance was 1-sided equals 0.1 for the most common assessments we have provided, 2-sided [indiscernible] 0.05 significance as well.

Next slide. Baseline characteristics are well matched for a Phase II study. Stratification factors were U.S. ex U.S. and 1 versus more than 1 immunosuppressant. Note, the MG-ADL and QMG are fairly balanced. Disease duration was shortest in the 300-milligram arm, which in this study was surprisingly a disadvantage as patients with longer disease duration had steeper declines in MG-ADL.

Next slide. Let's start with the Myasthenia Gravis activities of daily living or MG-ADL, which is a patient-reported outcomes measure. As you can see on this graph, impressive results with the 300-milligram arm achieving a 4.6 point decline versus baseline and a 1.8 point decline versus placebo and the 600-milligram arm achieving a 5.4 point decline versus baseline and a 2.6 point decline versus placebo. All of these results were statistically significant. However, the result was not statistically significant between the 2 treatment arms.

Next slide. Moving forward, here, we have the Quantitative Myasthenia Gravis Scale, or QMG, which is a physician-administered quantitative scale across 5 functions. Again, impressive and consistent results in both treatment arms versus placebo, with the 300-milligram arm achieving a 4.4 point decline versus baseline and a 2.4 point treatment effect versus placebo. The 600-milligram arm achieved a 4.5 point decline versus baseline and a 2.5-point decline treatment effect versus placebo. And again, all of these results are statistically significant versus placebo for treatment effect, but not different between the 2 treatment arms.

Next slide. Here, we see a rapid and statistically significant declines in the MG-ADL as soon as the earliest evaluation at Week 1 and at every time point in core. Next slide. And now we see a rapid and statistically significant decline in QMG as soon as week 1 and at week 13 in both treatment arms.

Next slide. The MG-ADL Christmas tree plot shows a robust effect versus placebo at all cutoffs in both treatment arms, with greater than 60% of patients improving by at least 5 points in both arms. Next slide. The QMG Christmas tree plot, similar to the MG-ADL plot shows a robust effect in both arms with more than 60% of patients in the 300 arm improving by 5 points or more. We also see some deeper declines in the 300 versus the 600 arm.

Next slide. MSE and MG is generally defined as an MG-ADL of 0 or 1. Again, we see a very robust response versus placebo with more than 1/3 of 300-milligram patients achieving this important milestone and the 300-milligram arm achieving significance on this metric versus placebo.

Next slide. Next, we have the Myasthenia Gravis composite score composed of 4 metrics imported from the MG-ADL, 3 imported from the QMG and 3 unique to MGC and are composed of specific muscle strength assessments. As expected, on the left-hand side, given the MG-ADL and QMG results, MGC overall results are robust with a 5.6 treatment effect versus placebo for the 300 arm and a 5.5 treatment effect for the 600 arm versus the placebo arm. Looking at unique to MGC muscle strength scores on the right-hand side also reveals robust results in both arms versus placebo.

Next slide. Wrapping up individual efficacy results, we have the MG Quality of Life 15, a patient-reported outcome measure that scores 15 items across physical, psychological and social domains. Again, robust results versus placebo and in this case, the 300 arm achieving significance versus placebo.

Next slide. Finally, the efficacy summary takes us back to how I started this data presentation, impressive and consistent treatment effect versus placebo with statistically significant treatment effect across all metrics in the 300 arm.

Next slide. Now let's move to safety results. fairly comparable AE profile in the treatment arms versus placebo. Some highlights are balanced infections overall. There are no related serious infections in either arm and certainly, no infection suspicious in any way as driven by complement inhibition. Injection site reaction experience was pleasing with few patients having generally mild and singular events. There were more patients with an ANA of 1 to 320 or greater at any time point in RCT as listed in this chart. None of these patients exceeded a titer of 1 over 320. We use the 1 over 320 bar in this chart as our screening criteria allowed patients with an ANA under 1 in 320 to be randomized. The number of treated patients with an ANA of 1 over 320 declined at week 13, and there was no indication of autoimmune activation as witnessed by the fairly benign rash and arthralgia experience.

Next slide. This data set gives us and will give our PIs great confidence in proceeding with the Phase III study. Clearly, we're taking the 300 milligram Q2-week dose forward. We are also considering adding a 300-milligram Q4-week arm based on encouraging initial PK efficacy seen in OLE.

And with that, Marino, I hand it back to you.

Thank you, Sim. Next slide, please. I mentioned at the beginning how our efficacy data supports our goal of developing a best-in-class inhibitor for Myasthenia Gravis. As you can see here clearly, Claseprubart did extremely well when compared to currently approved C5 inhibitors on the MG-ADL, what will likely be the primary endpoint in our Phase III trial. Whether you look at the absolute reduction in scores or the placebo-adjusted improvements, Claseprubart performed as we had hoped. This despite having a relatively high placebo response when compared to previous complement inhibitor studies.

Next slide, please. And looking at secondary efficacy measures such as the QMG and MSE, which Sim talked about and comparing Claseprubart versus ULTOMIRIS, the #1 blockbuster C5 inhibitor that's still growing and still being used as a first-line treatment in Myasthenia Gravis, I think you will agree these results are very impressive and build our confidence that we may have a clearly differentiated and best-in-class complement inhibitor.

Next slide, please. I also mentioned earlier that the MG market is the largest of the 3 neuromuscular markets that we are pursuing with Claseprubart to maximize its pipeline and a product potential. But MG is just the first step as we build an exciting neuromuscular franchise with Claseprubart, leveraging its potential as a pipeline and a product and a best-in-class profile in the large and growing U.S. neuromuscular market, starting with MG with its large population as the foundation and then building on that with CIDP and MMN. These 3 indications represent over 150,000 patients in the U.S. alone as of today and will likely continue to grow over time.

CIDP is our next exciting opportunity for a highly potent and differentiated active C1s inhibitor like Claseprubart. Sanofi presented exciting Phase II data with its active C1s inhibitor, Riliprubart, demonstrating meaningful efficacy in CIDP. In standard of care treated refractory as well as IVIG [indiscernible] Patients.

These results were the first proof of concept for an active C1s inhibitor in any autoimmune condition and for any complement inhibitor in CIDP. Today's data in Myasthenia Gravis significantly increases our confidence that we have the right dose in CIDP and in the overall successful execution of the CIDP program.

And finally, MMN is a disease where the classical pathway plays a critical role in the underlying pathology as proven by Argenx in 2024 with their C2 inhibitor, Empasiprubart, which provided proof of concept for the potential of classical pathway inhibition in this indication. This is our only competition in this third indication as FcRns won't work in MMN. We see Claseprubart as very well positioned versus Empasiprubartd in MMN with its convenient subcu self-administered auto-injector target profile and high selectivity for the classical pathway supporting a more convenient option with a potentially reduced likelihood of infections.

Next slide, please. So looking ahead, the next year will be a catalyst-rich year for Dianthus. First, as Sim mentioned, we plan to initiate a Phase III trial in Myasthenia Gravis in 2026, evaluating, of course, our every 2-week 300-milligram dose, but also a monthly 300-milligram dose. Next, we continue to expect top line Phase II results in MMN and an interim responder analysis from Part A of our Phase III pivotal CIDP trial in the second half of 2026. We also look forward to 3 other external catalysts, including Sanofi's data from 2 Phase III trials of Riliprubart in CIDP and argenx' Phase III results from Empasiprubart in MMN. I expect their results should have positive read-throughs to Claseprubart and Dianthus as they have in the past.

As a reminder, we have a strong balance sheet with a cash balance of approximately $309 million as of June 30 to fund operations into the second half of 2027. Next slide. I will wrap up now with this slide that I believe highlights the vision we have for Claseprubart as we pursue the power of consistent control with just one click. This target profile, which is supported by our impressive Phase II results today, would position Claseprubart as a clear, best-in-class first-line biologic treatment across all our neuromuscular franchise.

With that, could we please open the call for questions.

[Operator Instructions]

And our first question will come from Alex Thompson with Stifel.

I guess maybe 2 from us. On the decision to potentially pursue Q2 week and Q4 week in Phase III, maybe can you talk about, again, the totality of the data that gives you confidence in Q2 week and then the preliminary OLE data around supporting Q4 week? And then maybe could you touch on what you're seeing from complement pathway inhibition across both arms in the study and if that is consistent with what your expectations were?

Thank you, Alex, and I really appreciate those questions. I think I'll hand it over to Sim.

Sure. So yes, we have a lot of confidence in the Q2 week 300 milligram dose. It starts with the fact that before we even started any of our programs, when we looked at our performance on various complement inhibition assays and the information that was publicly available on what was needed, we felt that the 300 milligram dose was the right dose and the 600 milligram dose was really just a piece of safety, if anything else. And so we went into this trial pretty much assuming based on everything we knew that the 300 milligram dose is going to be the right dose. Then what we saw in the study. So upfront, you look at the MG-ADL, and I'm sure a lot of people are going, well, why aren't you going with 600milligram? Well, that's just one piece of data. And it's one piece of data in a relatively small study.

When you look at the totality of the data, including the QMG, including the MGCC, including the MGC muscle scores, right? So when you look at all of that information and you tie it in with the MSE, which, of course, has become an extremely popular endpoint and way to look at patients with autoimmune disease, not just in MG, but across the board, you see the results don't point to anywhere to 600 milligram. So we look at it as more a vagary of a single endpoint in a small study rather than something that's showing a treatment effect of 600 milligram over 300 milligram. So that's one. Two, I think you asked me about what we were seeing in terms of PD and PK. Generally, very consistent with what we saw in our healthy volunteer study.

Think the other question was, what are we seeing in the OLE that gives us confidence, Q4 week is a good dose.

So I'm going to caveat all OLE conversations, right? We did a data cleanup on the core. And as you know, how these things go, we received our data a handful of days ago, right, on core, and then we looked into the extension to see where interesting questions might come to us based on our data. So we anticipated this one. And so we did a little bit of work here. And the reason we have a lot of confidence also comes from early signals in our OLE, specifically looking at the placebo arm. So in our extension, nobody received an IV load.

And we always knew, and I think we talked to several of you as we launched this adventure that the placebo arm was going to be interesting to us exactly because we don't have an IV load. And therefore, we're going to be able to see how patients perform going from 0 gradually up on the PK ladder. And what I can tell you is that the early signals in placebo are very encouraging. So in other words, at PK levels well south of what we are achieving in the 300-milligram subcu Q2-week arm, we are seeing signs of what looks like at least robust efficacy on MG-ADL in the placebo arm. So that's another piece of information that's guiding us to Q4 weeks.

If I could also add, Alex, we've been very consistent on our messaging that if we saw these 2 arms perform equally, then it would confirm what we suspected is that we're already -- those both doses are already at the top end of the efficacy curve. And the question has always been in neuromuscular conditions like MG, what level of inhibition of the classical pathway do you really need to achieve or the complement system, do you really need to achieve to have that kind of improvement we've seen historically with complement inhibitors. And so the message has always been if these 2 doses perform well, Q4 week is on the table.

I will say that Cemdisiran data from Regeneron at the end of August, their SNRI-based C5 inhibitor was eye-opening. The fact that they had a significant improvement on the MG-ADL, we don't have a lot of data, but it sounds like it was a positive trial using the MG-ADL, and they disclosed that they only achieved 75% inhibition of the complement system. That's, in a way, a groundbreaking bit of information that tells us that getting above IC90 was always really an artificial, if you like, goal. And so if achieving something like 75% or 80% inhibition of the classical pathway is enough to give you similar results, we're very confident that's what Q4 week would be doing. And remember, we have a 60-day half-life. So every 4 weeks or every 30 days is very much well within our half-life time line.

And the next question is going to come from Yatin Suneja with Guggenheim.

Two questions for me. First is on the baseline characteristics. I mean you did have a little bit of lower disease duration at baseline. How that might have impacted the result on the 300-milligram dose? So that's one. And second, if you can comment on the ANA positivity that we saw? It seems like dose-dependent, any DSDNA conversion there.

Yes. So in terms of baseline characteristics, intuitively, you would expect that lower disease duration favors response. That's not what we saw in this data set. So when we looked at our data set, actually, there was a relatively strong correlation between those patients who had longer disease duration and steeper declines in MG-ADL. So that was surprising to us. We don't know why, but that's what we saw. So it was not an advantage for the 300 arm in any way.

Then the second question was around ANA. ANA, yes, it does look like there were more cases in the higher dose arm than the lower dose arm. What I would say, though, is, let's remember, ANA without the context of specific symptoms, so without the suspicion of SLE driven by symptoms is pretty much a useless test, right? The specificity or the sensitivity of the test is incredibly low. There are quite a few healthy people who walk around with positive ANAs and never have an issue in their life. So we're not entirely sure what to do with this piece of information in the context of our molecule.

What's important to remember and the specific reason why we put adverse events of rash and arthralgia in our safety table is because we did not see any patients who had a hint or suspicious hint of developing any lupus-like syndrome and you would pick that up to these types of specific AEs. And I can say that we haven't seen that in OLE as of now either. The next question was, I think, around double-stranded DNA. In terms of the data we have presented, the one patient in the 300 arm was double-stranded DNA positive. Reminder, that patient also exhibited no symptoms consistent with any connective tissue disorder.

And I would just add that the track record now for all 3 C1s inhibitors is really comforting neither ENJAYMO or Riliprubart and now with our Phase II trial, Claseprubart, have ever reported any patient having any autoimmune activation or any drug-induced lupus-like symptoms. So this theoretical risk remains just that, theoretical. We have not seen anything that would hint at that happening in our trial.

And the next question will come from Gavin Clark-Gartner with Evercore.

I just wanted to follow up on the last point you mentioned, Marino, on the ENJAYMO experience on the different titers. I think in the FDA review docs, they outlined that up to 25% to 30% of patients had at least one SLE autoantibody on the panel turned positive. But without any clinical symptoms, there did not seem to be any issue in the FDA review. And in fact, they didn't really know what to make of this. I'm curious if you could elaborate on that any further.

Yes. I mean I'll take that piece. I think this speaks to the fact that the idea of looking at ANA and double-stranded DNA came from the very useful place of taking people who show up with a set of symptoms over time that can be fatigue, joint pain, a rash, I don't know, et cetera. And within that differential, you have lupus or SLE. Within that framework, checking an ANA at a certain titer and a double-stranded DNA is useful because it might guide you to a diagnosis of SLE. These molecules by themselves are not pathogenic. They don't cause any harm on their own.

So in that context, it's useful. I think what you're seeing from the ENJAYMO data, what you're seeing if you go out and screen a bunch of healthy volunteers, what you're seeing if you just go to a hospital and you take a bunch of sick people for different reasons, whatever it may be, heart problems, cancer, whatever, and you just go check ANAs and double-stranded DNAs, you'll find very high levels because for whatever reason, those disorders are just being healthy can sometimes lead to the presence of these molecules, but they're not pathogenic. I think that's what you're seeing in the ENJAYMO data for whatever reason, when you have a C1s inhibitor, you can get an increase in these molecules, but they don't seem to translate into a clinical issue. So I think that's what they've seen. I think that's probably what's being experienced by Riliprubart, and that's what we're seeing as well.

Can I add also, Gavin, what's interesting is when we saw at the end of the trial, what was the #1 reason for screen failures. I fully expected that it would be that patients were not AChR positive, which is the only patients we were randomizing. It was actually patients who were at 320 or higher titers on ANA. That was amazing. And it just says that the general MG population, a very high percentage have that, but yet they are completely symptomless when it comes to anything that looks like lupus and without a history of lupus. So it's just one of those things that just is frankly, clinically relevant in this situation.

All right. Great. That's super helpful. And I just wanted to quickly follow up on Alex's first question on 4-week dosing potential. So I don't see evidence of a dose response here, which I guess is the first step to figuring out if 4 weeks could be a viable regimen. But can you just lay out what your plans are for looking at the additional exposure response, PD response analyses from the blinded portion to support the 4-week dosing potential?

Yes. I think that part now is pretty straightforward. Once this rush of making sure we've wrapped up the core data and have communicated it properly is over, our attention is really going to focus on what's going on in the extension. As most of these studies go, a lot of your recruiting is somewhat back-ended. So what that means is you have a lot of people who kind of come in to the study in the second half of your recruiting period, and they're kind of going through the meat of the extension right now.

So what I would anticipate is really over the next like month or 2, having enough information to have a much more definitive position looking at the extension data, looking specifically at the placebo arm and how they're performing, not just on MG-ADL, but of course, on all the other metrics, which we haven't done yet, QMG, et cetera. And also making sure there isn't any additional effect in the 600 arm, which to my eyeballs tells me there isn't. We just want to make sure over time that there isn't, right? And so I would anticipate in the next couple of months with a more deep dive in OLE that we'll have a better answer on that.

Gavin, it's Marino. Let me also add. So that's looking internally, of course, at the data. My background as commercial -- having spent many of my years of my career at commercial, I'm looking outside as well at the competition. I'm looking at it, we have a very prone antibody with a 60-day half-life. I'm looking at the fact that 300 milligrams gets over 90% inhibition of the classical pathway, knowing that every 4 weeks, it's probably around 80%, let's say, and that's part of the calculations we'll have to make. And then I look at the Cemdisiran data from Regeneron. Again, that was groundbreaking, not because of the efficacy they saw. It's the efficacy they saw at a very low level of inhibition compared to our 300 milligram every 2 weeks. That 75% inhibition delivered for them. And it delivered for them even better than the combination treatment, which -- of 2 C5s, which got close to 99% inhibition on the Claseprubart pathway.

When I look at all this evidence together and again, the fact that 300 and 600 milligrams pretty much performed equally in this trial, I don't see what there is to lose to go for and add an arm of Q4 week. I mean if for whatever reason, that didn't work and it was Q2 week, okay, we're back -- we hit our target product profile, DUPIXENT like dosing and administration. But why not go further? Why not push that differentiation? I don't see any much of a downside, to be honest.

And the next question will come from Rami Katkhuda with LifeSci Capital.

I guess it's great to see validation of 300 mg Claseprubart as the kind of the appropriate go-forward dose in neuromuscular disease. Based on the results, are you expecting to include a Q4-week dosing arm in CAPTIVATE for CIDP or in MMN in the future as well? And then secondly, do you expect a higher proportion of previously FcRn treated patients in the pivotal Phase III trial for MG? And could that influence efficacy results at the end of the day?

Yes. Great. Thank you, Rami, and great questions. So let me hand over to Sim to take the second question, and I can come back to thoughts on dosing administration for our other indications.

Yes. So we would welcome having more FcRn patients in our Phase III study as long as they're appropriately washed out from drug and given the half-life is not all that long, that's not that hard to do. One of the things that we're running into is in many of the geographies that we operated in, in our Phase II study, it seems like quite a few countries in Western Europe have a lot more liberal policies in terms of prescribing FcRns and complement inhibitors in general because they tend to see the value of biologics in MG. So they are surprisingly well reimbursed and covered.

And what that means is that your usual source of patients from somewhere in Western Europe, in particular, right, where you have people who entered a study, an FcRn study they did well. They're off the study. They go through the extension. Now they're off drug and they're looking for something else to get, by and large, it's hard to find in Western Europe because those people are still getting drugs because they showed in the clinical trial that it works for them. So they continue to receive drug.

In other parts of the world, which we'll be expanding to, for sure, we're going to be looking for those patients. I don't think it's going to influence the efficacy because ultimately, they're going to have to meet the same criteria everybody else does. And also, physicians are intelligent, right? So they tend not to look at a patient even if they meet your criteria that you sit down. If they think there's something about them, and this is not the right drug for them that you're offering, they're not going to put them in the study. So if a patient had a particularly bad experience, for example, on an FcRn inhibitor, most physicians are not going to take that patient and plug them into a trial like ours.

On the first question, so for CAPTIVATE our CIDP trial, remember that Part A is an open-label 300-milligram every 2-week dose. So we'll have an opportunity over the coming months to see how patients are responding to that dose in CIDP and further evaluate whether we even need the 600 milligram in the randomized portion and also whether there's a Q4 week open and potentially in the future, do another trial for CIDP and test that Q4 week.

And for MMN, again, next year, we will have the results of our Phase II trial looking at 300 and 600 milligram. And again, there, if we don't see a difference in efficacy, that will open up the door and we see good robust results, of course, that will open the door for Phase III testing at Q4 week. But we still need to see more data. Those are different neuromuscular conditions. But what I can say is from this trial, it gives us confidence that, that 300-milligram target dose we've always had for all 3 indications is very potent and will work. That's my -- that's what we expect.

And the next question will come from Yaron Werber with TD Cowen.

Maybe just a couple of questions as relating to the loading dose and then your open-label extension, Marino. Can you just remind us the 2 loading doses? Are you seeing any differentiation between them? And which one would you advance in the Phase III? And then as you said in the OLE, the patients at that point who crossed over did not get a loading dose at the 600 milligram. What did you learn from that in terms of PK? I'm just trying to get a sense kind of how this would roll into future studies.

Sure. Let me hand that to Sim to talk a little bit about the loading doses and what we're seeing in the OLE.

Right. So the loading dose for the 600 milligram was 15 milligrams per kilogram and the loading dose for the 300 milligram was 10 milligrams per kilogram. Those loading doses were chosen in order to get us to steady state in an efficient manner. In other words, the steady state that would be achieved by these 2 regimens of Q2 weeks over long periods of time, right? It's just to get us there quickly. And so that's the rationale behind the loading doses. That's how it was explained to regulators, and that's how it kind of moved forward.

So what did we learn from our OLE? The reason I had mentioned earlier that the placebo arm and the OLE would be interesting is because you don't have a loading dose. The loading dose basically takes you to a higher PK immediately and then you come down very rapidly to your steady state, whereas not giving a loading dose allows you to go from no drug exposure whatsoever and gradually go through the various levels of PK. That's why when we look at, for example, OLE week 4, right, they've only received 2 doses of 600 milligram subcu. We know at that time point what their PK is. It's a lot lower than the steady state of 300 milligram every 2 weeks, and yet we're seeing substantial additional MG-ADL effect on top of the placebo effect these patients already exhibited during the course of the core study.

Yes. Let me just correct. It's 15 and 20 milligrams per kg loading dose. Just remember, if you look at the DUPIXENT target product profile, which we've said is always our target for dosing administration, they have loading doses with multiple subcu shots Day 1 and then at Day 7, start self-administering DUPIXENT every 2 weeks. Extension, that's what we're aiming for in our label. We're just using an IV in clinical trials because it's just simpler, but we're working with the FDA on how we translate that into subcu self-administered auto-injector shots that the patient could give themselves over the first 1 or 2 days. And then at day 7, they can start self-administering every 2 weeks. So I just wanted to clarify that point.

And our next question comes from Myles Minter with William Blair.

I think investors are just debating like why you're taking 600 mg off the table for the Phase III at the current time. Can you just talk a little bit about how you balance like the data that you saw that shows equivalent efficacy with 300 milligrams versus like the safety, in particular, the ANA that popped up in 600 milligrams versus 300 milligram versus maybe trying to maintain differentiation versus Riliprubart. I just think that there's debate over those sort of 3 factors as to why you're moving with 300 mg in a Phase III. So any clarity there would be great.

And then secondly, just on the safety profile, the infections that you did see in the trial, it looks like less incidents in the Claseprubart arm. So just wondering whether we should make anything of that, that seemed interesting to me.

Go ahead, Sam.

Yes. So I'll start with the infections. Yes, I mean, again, if you look at the numbers, you would say 10% versus 5%, et cetera, like higher incidence of infections in the placebo arm. Of course, that doesn't mean anything, right? I mean complement inhibitors are almost certainly not protective against infections. I think the best you can take away from that is that as we expected, complement inhibitors, if there is a risk of infection, it's a very specific subset of infections, so not a broad set like viral infections. So you don't tend to see this broad infection signal, and that's exactly what happened, right? These doses of Claseprubart, the infection rate was essentially equivalent regardless of the numbers being higher in placebo.

What's more important to me on the infection side is the fact that there were no serious related infections, right? That's really where I think the data pops that in the course of this study, there was nothing that could be tied back either by investigator or ourselves to the fact that the patient had a serious infection and that was due to a complement inhibitor.

In fact, the only one that we saw was a UTI in a relatively debilitated patient that was related and serious because they were hospitalized and it ended up being in the control arm. So I wouldn't make more of it than that. There's just -- it doesn't seem like in this study, Claseprubart was accountable for any infection risk above and beyond placebo.

Then in terms of, again, why 300 milligram? Well, I'll say a lot of what I've said before. We have to look at the totality of the data. So just like with infections, if you took a look at just that one overall arm, you'd say, well, yes, the numbers are a lot higher in placebo. What does it mean? It doesn't mean anything. It just means there are 22 people in the study. That's all, right? And I think it's the same thing with the MG-ADL. It only takes 2 or 3 people who maybe weren't responders to anything in the control arm to drive a result. You have to look at everything else.

And I think I put a lot of weight on the QMG. I also put a lot of weight on the muscle sum scores in MGC, which is on one of the slides on the right. And the reason for that is that is looking at the same types of metrics 2 different ways, shoulder strength by resistance and shoulder strength by endurance.

And so when you start to see these very consistent results, both on MGCC and on MSE -- on MGC muscle strength and on QMG and then a higher rate of MSE in the 300 arm as well, that's kind of what's guiding us to 300 milligram. Now of course, you always want to go to a lower dose, right? If you feel like there isn't an efficacy penalty or a substantial one to pay, you always want to use the lowest possible dose because I don't care what drug you give, if you're able to give less, you will deliver less problems to patients in the future for sure.

So part of what we have to do is also try to find that minimum effective dose. And I think that's a piece of going to Q4 weeks. But the Q3 -- the 300 milligram Q2 weeks in my mind, when you look at the entire strength of the F data, which is why we've shown you so much information, seems to be very, very equivalent to what we're seeing with the 600 arm.

Yes. if, I can also just reiterate, maybe if we can pull up Slide 26. Remember, our target product profile has always been to differentiate ourselves and be able to win in the MG market is to deliver the most convenient, the most patient-friendly dosing administration and DUPIXENT every 2 weeks autoinjector was -- has always been our goal. And that achieves very potent inhibition of the classical pathway. And if I can pull up Slide 26, if possible.

When I look at the MSE there on the right, that is the highest minimal symptom expression rate ever seen with a complement inhibitor, period. And when you look at it, how it compares to Ultomiris, that is very, very impressive. And frankly, that's probably the goal when you're treating these patients is to get them to a point where they are not thinking about their disease, where they're not feeling the symptoms and 300 milligram did better. And so this gives us a lot of confidence that 300 milligram is absolutely the right dose. And again, there was no statistical significant different effect on the MGDL between 300 milligram and 600 milligram. So at one point, we were asked if we didn't hit stat sig, would we combine the 2 doses. We didn't need to do that here. But if you did, you see a nice north of 2-point difference for Claseprubart. And that's what we fully expect we'll see in a larger trial going into Phase III with 300 milligrams every 2 weeks.

And I would now like to turn the call back over to Marino Garcia for closing remarks.

Thank you. And thank you, everyone, for your attention and joining us today. Really appreciate it. I look forward to engaging with some of you as we go forward from here. But again, I just want to thank Sim, the Dianthus team in general for a very well executed and timely study.

I have to say we were hoping to see these types of results, confirming the 300-milligram Q2 week as a classical pathway inhibitor would work in Myasthenia Gravis. It's a first proof of concept. We've already got proof of concept from other classical pathway inhibitors in CIDP and MMN. So overall, for this neuromuscular program, we feel like the level of risk has been significantly reduced. And it's really giving or bolstered our confidence as we move forward in developing this very potent antibody in MG as well as CIDP and MMN. And I look forward to providing further updates as we go forward.

Thank you very much.

This concludes today's conference call. Thank you for participating. You may now disconnect.