Good afternoon everyone. I'm Alex Thompson, biotech analyst here at Stifel. Very happy to have Marino Garcia here with us this afternoon, CEO of Dianthus Therapeutics for a fireside chat. Maybe Marino, I'll kick it over to you for a quick intro to Dianthus and then we'll get into a Q&A.
Sure. First off, Alex, thank you for the invitation and the opportunity to do this Q&A or a fireside chat with you today. So Dianthus Therapeutics, we're focused on building a really cool biotech company in the autoimmune space. We have two programs. Our lead program, Claseprubart, is a very potent active C1s inhibitor. We just read out really exciting phase II MG data, Myasthenia Gravis data in September that validates the original concept behind Claseprubart, which is as an active C1s inhibitor.
A very potent active C1s inhibitor with an extended half-life of 60 days was to deliver best-in-class efficacy in conditions driven by the classical pathway of the complement system like Myasthenia Gravis, with an improved safety profile over current complement therapies like the C5s, like ULTOMIRIS, the leading C5 inhibitor in Myasthenia Gravis, with a lower risk of infection from encapsulated bacteria with the potential for no box warning, no REMS program in the label around the risk of meningitis, and then finally with a very infrequent SubQ auto-injector self-administered dose. We tested every two weeks in phase II and saw it was very effective. We did not see a difference in dosing between the high dose and low dose or a target dose.
We're now going to be moving forward with our 60 day half-life to test in phase III, both every Q2 week dosing with one shot 300 mg 2 ml and at every four week dosing. Based on that Myasthenia Gravis data, our target product profile now for MG is equal or better efficacy to C5s, a better safety profile with no box warning and no REMS, and Q4 week dosing, at worst every Q2 week dosing, which would definitely make it a best-in-class excellent first-line therapy. We're also developing it in CIDP, Chronic Inflammatory Demyelinating Polyneuropathy, as well as MMN, Multifocal Motor Neuropathy. Our CIDP program is a single phase III trial. We just recently announced that we are moving up our timelines for our interim responder analysis. Originally it was second half of next year.
We're now going to be announcing that in the second quarter of 2026. And MMN is still on track to top line results for phase II for second half of 2026. We did a nice raise on the MG data in September. So we now have about $525 million with runway into 2028 between then and now. We also announced that we have in-licensed a really exciting Bifunctional Fusion Protein from Leads Biolabs in China. It targets both BDCA-2 as well as BAFF /APRIL. So the innate and adaptive immune system. And the idea here is to take this unique therapy first in class, potential best in class. Also product in a pipeline like pipeline in a product like Claseprubart is to take it into diseases where there's clear evidence that both the innate and adaptive immune system are contributing to the disease.
The idea is to be able to bring superior efficacy, better efficacy, synergistic efficacy or complementary efficacy in those diseases compared to any one approach, whether B cell approach or type one interferon approach. That is ready for the clinic. The IND has been cleared in the U.S. It will be cleared in China any day now. We will then be starting a phase one in healthy volunteers and we'll have results for that in second half of 2026. Along with our prioritization of indications in our corporate deck, you can see the list of indications that we're going to be deciding which ones are our top three priorities from. Every single one of those indications and markets are very exciting. Huge unmet need.
Importantly, it's where we see clear evidence that both the innate and adaptive immune systems are at play in that disease where this therapy can bring superior efficacy compared to any one monoclonal approach.
Great. So lots going on. Yeah.
You asked.
Maybe taking a step back, I want to kind of zero in on this idea of classical pathway inhibition and why that's uniquely differentiated from a lot of these terminal pathway inhibitors that are out there today. Like why is that an exciting target in autoimmune diseases?
First, when you look at a market like MG, there are, in terms of the complement class, only C5s approved terminal inhibitors and there are only C5s in development for Myasthenia Gravis. They're very effective at preventing the formation of the Membrane Attack Complex or MAC, which is the primary driver of disease or dysfunction at the neuromuscular junction. The issue with terminal inhibitors is that they also shut down the lectin and alternative pathway and prevent those two pathways from forming MAC. In order to fight against the risks of infections or deadly infections like meningitis, we leave the lectin and alternative pathways intact and that means we have a lower risk of serious infections, deadly infections. ENJAYMO sutimlimab is a C1s inhibitor that's approved on the market today. It's only approved for Cold Agglutinin Disease. Sanofi recently sold it to Recordati for $1 billion.
That is the only complement inhibitor on the market that doesn't have a box warning or REMS program. That is a precedent already set. It targets C1s. We target activated C1s so it's the same target. We leave alternate and lectin pathways intact, so deliver complement inhibition in a safer manner. Secondly, there's also potential here for superior efficacy over C5 terminal inhibitors. Why? Because we have this now. We shared it at the AANEM. It was presented at AANEM in San Francisco this past month in October. By being an upstream inhibitor versus a downstream inhibitor, the additional potential efficacy we can extract is by preventing the formation of these toxins. These pro-inflammatory split products that are created, C3a and C3b. With someone who's on a C5 inhibitor, terminal inhibitor for Myasthenia Gravis, you're preventing MAC, which is really important and the primary goal.
Unfortunately those patients still have C3a and C3b split products. These pro-inflammatory toxins are being created and deposited right there at the neuromuscular junction. Those obviously cause some damage over time and we are able to prevent that by stopping the complement cascade earlier at C1s. We demonstrate that very clearly versus ravulizumab in our slides in our corporate deck. That is an in vitro experiment, but it makes sense. If you look at ENJAYMO's label, it is approved for Cold Agglutinin Disease. It is the only C1s inhibitor approved. How does it work in Cold Agglutinin Disease? Cold agglutinin disease is a C3b-driven disease. It is C3b being deposited onto the red blood cells and causing damage. ENJAYMO prevents that because it is a C1s inhibitor. It makes sense we do that.
We now clearly show in our post hoc analysis, and it's also presented at ADM, that with an MGADL of six and above screening criteria and a QMG of 10 screening criteria, when you look at our phase II data, we get to a three point difference on the MGADL versus placebo. No therapy has ever shown that on the market. No approved therapy has ever shown that kind of efficacy. We fully expect that we will see better efficacy than C5 of demonstrating MG in our first phase III trial with these cutoffs, with these screening criteria.
Yeah, and I want to spend a little bit more time on the phase II. I think specifically the question is, why did you test two doses in the MG study?
When we were a young company and private trying to raise money, it was very clear that what investors wanted to see is that we were testing doses that get above IC90 as measured by the CH50 hemolytic assay and even another second dose that got above IC95. Why we had to achieve those targets, nobody really knows, nobody ever really tested what level of inhibition you really need to achieve to see efficacy in neuromuscular conditions like Myasthenia Gravis. We said, okay, we need to do that. To do that, to get with a 60 day half life of potent antibody like ours, to get above IC90, we needed 300 milligrams, one shot, 2 milliliters every two weeks. That gives us the kind of accumulation, that peak trough. We are well above the target IC90 levels required in humans.
To get above IC95, we just doubled the dose, 600 every two weeks. We always believed that, a, we were not going to see a dose response between those two doses and we did not. In the MG trial we also suspected we were giving too high a dose. In our phase II Myasthenia Gravis trial, we had a little mini experiment designed into it, including the larger phase II experiment, which is what we did is for placebo patients, once they finished the 13 weeks, we allowed them to go into the open label, we started giving them Claseprubart SubQ but no loading dose. The reason is we wanted to see, as PK levels start going up after every week, every dose every two weeks, what kind of MG-ADL and QMG impact did we see?
If you look at our slide deck again, it was presented at AANEM. These patients, after having had already a robust response on the QMG and the MG-ADL while on placebo in the first 13 weeks, they had another very significant, very, very material drop in the MG-ADL and the QMG at much lower PK levels than 300 mg every two weeks gets you to. Bottom line, 300 mg every two weeks, your steady state with Claseprubart will be somewhere around 100 to 120 micrograms per milliliter. We saw a 2.5 drop on the MG-ADL in the open label portion above and beyond the 2.8 we already saw in the randomized control portion of the trial at PK levels that were about half of that.
That tells us that dosing every four weeks, getting to PK levels like somewhere in the 50-60-65 range micrograms per milliliter could still deliver efficacy. I want to just point out cemdisiran is a C5 inhibitor being studied by Regeneron. They came out with data in August just before our data that showed a 2.3 improvement after 26 weeks, I think it was, or about six months on the MG-ADL. What I'm really appreciative of from Regeneron, so thank you to them, is that they did not say much about the data except that they had statistically significant improvement on the MG-ADL. They added one other really important piece of evidence or information. They only achieved 75% inhibition of the classical pathway. That is the first time we have seen a complement inhibitor show significant efficacy on the MG-ADL at levels as low as 75% inhibition.
It proves, I believe the evidence is building that you do not need to get to above IC90 in neuromuscular conditions. For us there is no reason, we believe that with a 60 day half life with the potency we have, with the evidence we have from our open label as well as the evidence from our external parties like Regeneron that a once a month dose of Claseprubart will work in MG-ADL just as well as every two week dose. Again in our phase III, just like in our phase II, I do not expect a dose response. I fully expect we will have a once a month auto injector self administered for MG on the market when we get approved, if we get approved.
A couple more questions on MG, you know, I guess on safety. How comfortable are you now with the safety profile? Just from the phase II and the OLE, ICE in particular. Are you at all concerned about the formation of antinuclear antibodies in patients?
It's a good question. So you know there are three C1s inhibitors in development or approved. We have ENJAYMO approved for Cold Agglutinin Disease. They have been on the market for three and a half years and their dose is 6,500 mg- 7,500 mg per every two weeks by IV. It is, I believe, the highest dose antibody on the market. It's 25-50x higher dose than what we're aiming for. In MG, they had no cases of lupus-like symptoms. Which is what I think you're getting at. Right. Is, is there any risk of autoimmune activation? They have no drug-induced lupus cases in development, none reported on the market in three and a half years. They check for ANAs and they had some elevations of ANAs. Yep. LiptoBART, same thing. They saw ANAs in their phase II.
Now in phase III, they've stopped screening, they've stopped testing for it. They have agreement with the FDA because like with us, LiptoBART looked at the ANA data and said, this is not really telling us anything. It doesn't really help. ANAs in the absence of clinical symptoms really don't tell you anything. They're not pathogenic on their own. In the real world, the only way you use ANA testing is if someone shows up and it looks like they might have lupus and you're not 100% sure, you test their ANAs to help you build confidence that diagnosis is correct. ANAs are not used for screening. We tested for ANAs because it's our first trial and the FDA said, how are you going to check for potential risk of autoimmune activation? We did, well, let's do what ENJAYMO and LiptoBART did.
We did it and just like them, it's not really telling us anything. We had zero cases of any patient having any symptoms of any that look like an autoimmune disorder. There's no activation of autoimmune disorder. We had no patients develop meningitis or encapsulated bacterial infections. I feel really good about the safety profile. We're move forward in phase III. We're going to talk to the FDA and do the same thing that LiptoBART's done in phase III to stop screening. The number one reason we had for screen failures into our MG trial was patients with elevated ANAs. That's something not many people, nobody knew that MG patients are walking around with elevated ANAs and they have no history of lupus, no history, family history of lupus. We don't know why they have high ANAs, but that was a surprise to us.
We could have finished our trial even sooner if we hadn't screened for MG patients for ANAs and investigators told us, stop doing that, stop making us test for it. We feel really good about the safety profile.
Let's move on to CIDP.
Sure.
We have some data from Sanofi's LiptoBART and CIDP showing activity here. What gets you excited about Claseprubart in CIDP and can you talk about your trial design?
Sure. Why I'm excited about CIDP again thanks to an external, Sanofi this time, is when you look at their data, you see from their phase II data they took patients who are stable on IVIG and doing well and switched them immediately. They didn't make them relapse like efgartigimod or the FcRns do in their trials. They switched them right away and 50% of patients got better. Better than what they were doing on IVIG. Patients who were refractory on IVIG, those are patients that FcRns exclude from their trials because they don't expect to see efficacy in patients if IVIG didn't work. IVIG is a superior, more efficacious option. It's just FcRns are better tolerated, more patient friendly. They excluded those patients.
Claseprubart allowed the refractory patients from IVIG to come into the trial and 50% of patients improved even though they were not doing well on IVIG. To me, what that signals is that there is a potential here for active C1s inhibition or classical pathway inhibition to be more effective than IVIG. That is exciting because IVIG is a lifesaver for patients. It works for a lot of patients. The tolerability, the dosing, administration is really a big burden. If you can take the burden away and potentially even provide better efficacy than IVIG, that is a game changer in CIDP. FcRns are a better tolerated version of IVIG, but they are not as effective as IVIG. That makes me very excited for classical pathway inhibition. What is interesting then, based on that data, Sanofi is doing a head-to-head trial versus IVIG in CIDP.
You do not, as a company, do head to head trials versus a gold standard efficacy treatment unless you think you're going to win.
Yeah.
And what I. And so that's great. They feel very confident in their data. What's even more impressive for me is when you look at Argenx, who are in the CIDP market with the number one blockbuster FcRn efgartigimod. They have a complement inhibitor in their pipeline, Empasiprubart, also being studied in CIDP. Only one of those two products is doing a head to head trial versus IVIG and that's Empasiprubart, and I think that speaks volumes. You only do a head to head trial versus a gold standard therapy in any disease if you think you're going to win. They are taking their complement inhibitor into head to head trial versus IVIG in CIDP.
Yep.
That tells me two companies that obviously know what they're doing and have a lot of credibility that they expect to see potentially superior efficacy for their complement inhibitor versus IVIG. I'm really excited about that. I hope that they prove that and that could be a complete treatment paradigm change in CIDP where you could have complement inhibition, specific classical pathway inhibition or active C1s inhibition as the first choice due to superior efficacy, better tolerability, safety as well as more convenient dosing than IVIG.
You're running a trial similar to the Argenx trial. You're not letting patients wash out and worsen. That's really not part of the field anymore. You are going to have an open label responder portion. You're going to have interim analysis now in the first half of next year. What do you want to see in that interim analysis? How should we think about what to expect heading into that update next year?
We want to see similar efficacy at least compared to LiptoBART's phase II open label. Anywhere in the 40%-50% response rates in those first 40 patients tells us we're in the game. We are similar to LiptoBART. We have a more potent antibody. I don't know if we can see better efficacy because I don't know where they are on the efficacy curve. Are they already at the top end or are they somewhere on the slope where we could potentially, with a more potent active C1s inhibitor, deliver more efficacy. Base case, similar efficacy to LiptoBART but one-fourth the number of injections. Upside case is better efficacy.
What do you plan to share with the interim analysis?
The FDA would really like us to only say go, no go.
Yep.
That's what Argenx did.
Yes.
I would like to share more. Okay. And knowing very full well that no matter what I share, people are going to want to know more. But I want to be able to tell you as much as I can. We are working with regulatory experts as well as lawyers to see like what can we share without affecting the integrity of the trial and making sure the FDA does not get upset.
Okay.
Look, at a minimum, Alex, you are going to see two things, and that will be in clinical trials and probably on our slides. What is the end we are aiming for in part B? And understanding that only responders in part A are going into part B. What is the end we are aiming for in part A?
It's a very simple division. Right now it's about, we're assuming 40% of patients, at least in part A, are going to go into part B. If we keep that the same or make it half the patients or, you know, that'll tell you what are we seeing in those first 40 patients. The ends alone in the clinical trial design should tell you what are we aiming for as a minimum for efficacy based on what we're seeing in the phase II, and therefore what kind of recruitment do we need?
You also, you know, with your update here recently, you moved the interim analysis from second half to 2Q. That's sort of also in the context of Sanofi pushing back the timeline of their CIDP phase III program.
Yeah.
How do we mesh both those things? How is enrollment going for you?
Yeah, you know, it's interesting. Enrollment was going very well for us and on track this year. We had the MG data. We did not just share that MG data with the public and with MG physicians in our trials. We shared it with our CIDP and MMN investigators as well, because it's an allied disease in the neuromuscular space. We knew they were interested in knowing the data. The reception from those physicians was very, very positive. What we saw is what was already a very positive sort of recruitment curve all of a sudden do a bit of a hockey stick. I think anecdotally what we are hearing or we heard is that some physicians were kind of like curious to see the data before they really started recruiting aggressively for us.
What they saw was very, very reassuring, both on the efficacy as well as the safety front. We saw acceleration in recruitment and it was looking really good. All of a sudden Sanofi comes out with their earnings and says, we're delaying our trials now for a second time now into 2027 for top line results. Of course, I got a lot of questions from such as yourself and investors. I was truthful. I said, no, we're on track, we're not going to be delayed. I know people worried, but if anything, I was seeing that our recruitment was accelerating and that we were starting to look like we were going to be in the first half, not second half.
Okay.
So by the time we got to about a week and a half ago or close to our earnings release, we realized, okay, yeah, this is definitely going to be in the second quarter at the latest for 2026. That's why we updated our guidance. Look, it's not just that the MG data really excited physicians and encouraged them to put more patients into our other trials. It's also that it's the most attractive trial because everybody goes into open label, gets drug. There's no question, there's no randomization, blinded chance of getting placebo. Only if you respond in our drug do you go into part B, and it's once every two weeks versus every week with Sanofi. It's just an easier trial to be a part of.
Makes sense. We have a little over six minutes left. I want to touch on MMN and 212. Maybe for MMN, I think the question is, you know, it's certainly been the indication that folks have paid less attention to for Dianthus at this point. You know, what's the pitch on why this is an interesting market that folks should pay attention to ahead of phase II data next year.
Imagine where we have an indication MG and we're doing well there.
Yeah.
Then we have the CIDP indication and we're doing well there. We don't have to go to new customers for MMN. MMN just gets layered on top. Yes, it's a smaller market, but there's only one other therapy in development. FcRns don't work. It's IgM driven. The only other therapy is the C2 inhibitor from Argenx. The C2 inhibitor? Yes, it blocks the classical pathway, which is what you need to be effective in MMN, but it also blocks lectin. Very high likelihood of getting a box warning and a REMS program around the risk of infection. It's an IV.
Yep.
That's it. There's nothing else.
Yes, it's a smaller market, but with the same infrastructure that we would have for MG and CIDP, we now can get a much bigger slice of a smaller market, but a much bigger slice of a third market. That is MMN. We will have the advantage of the efficacy, the no box warning and REMS program, and an auto injector at most every two weeks.
Yep.
I'm really, really excited about that opportunity. By the way, we're going to talk more about it in 2026. Let's remember, MG was supposed to be only a 40,000 patient market like 10 years ago, CIDP was only, whatever, 20,000 patients a few years ago. The more a disease gets attention, the more treatment options start becoming or developed or available, the more you see diagnosis increase. I fully expect the same thing can happen with MMN.
212 . There's a lot more obviously beyond these three indications for C1s that you could do. Why add another pipeline program?
Look, the vision from the beginning has always been to build a self-sustained, exciting biotech company. No matter how exciting your one program, how much of a pipeline or product potential it has, it's not enough to build a company for the long term. We always had in our minds that we wanted to build a pipeline. I'll be honest, like, you know, two, three years ago. We did have two earlier programs, but they were so early they were not really worth disclosing. We killed them because we didn't think it had the same characteristics as Claseprubart, that best-in-class, highly differentiated, you know, really strong commercial potential in the future. We killed them. Our BD focus really ramped up in the last couple of years. Our team went through 180 programs.
China, Europe, US, everywhere you could imagine, academic, other companies, et cetera. When we saw this bifunctional fusion protein 212 that targets both the innate and adaptive immune system. It has that first in class, best in class pipeline in a product, highly differentiated, the potential to deliver superior efficacy, great safety that we already understand from the two mechanisms and the potential for every four week or every eight week dosing, sub Q auto injector potential. We said this is the same value proposition as Claseprubart. We said it makes sense, this is the time to add it. On top of that we add it to our pipeline, it's ready to go into the clinic and it doesn't affect our runway. We got great terms for it.
It is a real win win for us and Leads Biolabs who just went public this summer in the Hong Kong exchange. It was the perfect timing, the exact right program to add to our pipeline to really continue to build more catalysts and continue to build value over time.
I guess the one theoretical question here is blocking the innate and adaptive immune system. Both of these targets are relatively safe but have certain risks, particularly around infection. Are you worried that adding them together might lead to something much worse?
Obviously, no, we're not because obviously we wouldn't have executed on the trial. We'll have to see, we'll have to see what the healthy volunteer phase one studies show us. At this point, no, we don't really think there will be any new safety signals. We expect that it will be the same as you would expect with either mechanism.
Yeah.
Any initial thoughts on indications?
Yeah, we have a slide where we have put in those indications that make sense for this dual mechanism. Like we have the APRIL/BAFF side. You do not see IgAN on that list. The reason you do not see IgAN in that list is because we do not think the innate immune part of it plays a role. What would be the benefit of us reducing Type I Interferon for those patients? That list has things like SLE, like dermatomyositis, like Sjögren's. It is diseases where there is at least some scientific rationale for both mechanisms, the innate and adaptive immune system playing a role in the pathogenic. Where we think something like this could bring additional complementary efficacy over any one monotherapy approach. When we shared this product with KOLs, especially SLE KOLs, what they said very clearly is, this is exactly what we are waiting for.
I want to be able to use two antibodies that target the adaptive and immune, the type 1 interferon as well as the B cell approach. We want to use those, but we can't in the real world. If you guys can deliver that in one therapy, that's exactly what we need. That got us very excited.
Great. Maybe lastly, with your runway that you have now, what readouts do we get within that?
Yeah, so obviously the readouts from next year, readouts into 2027. Multiple readouts with 212, which we'll update everybody on for 212. We expect healthy volunteer data in the second half of next year. Obviously, our prioritized list of indications, as soon as we've done the work on that, we'll have MMN data by the end of next year with our phase II, and we'll be able to kick off the phase III MMN as well for that.
Great. Marino, thank you so much.
Thank you, Alex.