Biotech Summit 2026. My name is Yatin Suneja. I'm joined here with my colleague, Delma Khayati. We will be moderating the next discussion with Dianthus Therapeutics. From the company, we have two executives here. We have Marino Garcia, who's 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 comment, and 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 DNTH212 from Leads Biolabs in China, a potential best-in-class product pipeline and a product that bifunctional fusion protein that targets BDCA2 on one side to reduce type I interferon and BAFF/APRIL on the other side.
In vitro and in non-human primates, it looks like it may be, you know, more potent than litifilimab, which is in Biogen's portfolio, and being studied in SLE on the Type I interferon reduction side, on the pDC depletion side. And then on the other, on the BAFF/APRIL, it looks like we have deeper, longer depletion of IgG, IgA, and IgM compared to povetacicept. So we now have two products in the clinic, and we started off 2026 with two major catalysts coming for clasiprubart, 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 2 trial back in September.
Those two catalysts are, we have our CIDP phase 3 single study, Part A 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 2 top-line results in the second half of this year. And with DNTH212, the next catalysts are in the first half of this year. We will have clarity on which three indications we're gonna go after, to maximize its pipeline and our 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 then we'll have the second part of that SAD study is actually testing three 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 catalyst investors are focused on. So for the Captivate study, 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 so, I think people, investors understand that Captivate is a unique study, different than the ADHERE study that we've got, or argenx ran. So just frame that for us.
Sure.
Yeah.
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 2 phase 3 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 2 data, where they saw in patients who are on IVIG and stable or IVIG refractory standard care, stable or standard care, refractory. They, 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 3 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 wanna 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 gonna have, one quarter less the injections, that riliprubart, doses. So they're dosing 600 mg 4 mL a week. We dose 300 mg 2 mL every two 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, two 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, you know, above the IC90 or similar potentially efficacy. So we're looking in that part A to see similar results to what riliprubart's on their phase 2 study. Anywhere around 40%-50% or greater efficacy.
And that means patients who are 40%-50% of patients who see an additional improvement of one 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 one 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 gonna 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," 'cause that, in the end of the day, is what's required to go to market and compete effectively. What I'm gonna 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 at—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 three arms: placebo, 300 milligrams every 2 weeks, and then we have 600 milligrams, a higher dose.
Did we get rid of the 600 milligrams arm, 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 3. They keep delaying their time to BLA, while we're accelerating our timelines. We're having the opposite experience with our trial.
If we cut this trial down by a third 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.
Again, as I mentioned, we're looking for at least a 40%-50% responder rate in those first 40 patients to 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 three 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-
Yeah.
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 gonna 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 or 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's ever gonna do trials like that anymore. We switch them within seven 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 efgartigimod, they're doing the same: switch within seven days. There's no need to wash them out and make them relapse.
Then finally, that 67% responder rate that argenx saw with efgartigimod in Part A, remember, that's after patients relapsed, when taken off of IVIG. Patients were, are stable on IVIG, taken off, relapsed, and then only those put into Part A, and that means two-thirds of patients were able to get back to stable as they were on IVIG before. That means a full third didn't get back to where they were with IVIG. When you look at the riliprubart data, for those stable patients on IVIG, they were switched right away, no relapse-
Mm-hmm.
... 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.... 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, then I'll hand it over to Delma. So I think the biggest change I have noticed is, at least for the CAPTIVATE study, the possibility of dropping the 600 milligram arm, right? That would make the trial more efficient, faster, whatever, however you term it. What is underpinning that potential? Like, why? Is it the GMG-
You know, 300 milligrams or every two weeks with us, we know gets above IC90-
Mm.
-on the CH50 assay. It's really potent. We saw in MG that there was no dose response between 3 and 600. There's no benefit in that neuromuscular condition to be above IC95, for example. We now have some Dianthus data on MG that shows that at 75% inhibition, they still had a 2.3-
Yeah
improvement on the MG-ADL, and therefore had good efficacy. So there's no evidence in neuromuscular conditions that you have to be that high a level of inhibition. So, we really doubt 600 milligram is gonna add any benefit.
Okay.
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 CH50 milliliter assay. I believe they're achieving that data with a lower level of inhibition than we are doing with 300 milligrams every 2 weeks.
Okay, so you don't need to. Delma?
Yeah, maybe turning to the MMN program now. So we can consider that indication as largely de-risked by C2 inhibition and empasiprubart from argenx. And the key point is that how can you differentiate from that?
Sure.
Both mechanistically, so is there any expectation that you can show higher efficacy than EMPA? And also in terms of safety, convenience.
Sure. So, you know, 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 an IV every month-
Mm-hmm
... we're gonna be a sub-Q self-administered auto-injector every two weeks. So that's a clear advantage for the patients. And we also believe we're gonna have a safety advantage because they do block the classical pathway, which is where all the efficacy of MMN 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 two 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 four years and has no box warning, and that's a pure classical pathway inhibitor. So, there's gonna be at least, I think, a dosing and safety advantage. On efficacy, we finally saw empasiprubart or argenx publish 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 the assay that they published in." And they only published the IC50 as well. And when we ran that test multiple times, we get similar data for them than what they publish. Actually, it looks a little better in our hands.
Mm-hmm.
At IC50, we're at least 6 times more potent. Now, if you look at the curves on the slide, if you said, "Well, you need to be above IC90, what, what was that?" 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've published." But in our hands, in that experiment, at IC90, we're 30 times 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.
Mm-hmm.
We know that with MG, 75% inhibition now looks like it's 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 achieve with every two-week dosing, which is what we would get at every four-week dosing, we've seen, you know, really good responses from placebo patients going in on open label. So, at a minimum, we expect similar efficacy to riliprubart and empasiprubart. Our experiments, our data, when we, you know, 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.
Got it. Okay, and thinking ahead to the commercial perspective, what would be winning for you on a hypothetical scenario where both EMPA and clasiprubart work? So how do you see the competition in the market-
Yeah
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 need something to help them. And so if we have similar efficacy to empasiprubart, by the time when we're approved, there's only gonna be really two options for these patients of efficacious biologics.
Mm-hmm.
It'll 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 Halozyme. It's a 2-milliliter, 5-second click, done. You don't see the needle, very easy. 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-1 s, for example, and no box warning.
Mm-hmm.
I think it's gonna be pretty clear. I mean, I don't see a physician talking to an MMN patient saying, "Okay, there's a complement class that'll work really well," let's assume they're approved and work really well. There's one that's an IV, you know, once a month, whatever, and then there's another one, auto-injector. They're gonna 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 one, two, or three 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 smaller than CIDP, and if you look at efgartigimod, you know, that's double the price of MG, and that means there, you know, could be, you know, pretty high six-digit number per year in CIDP and MMN. So that, that, that could be another place where we might have a bit of an advantage.
Okay, thank you for that. Maybe, turning to the MG program in the interest of time. Did you have already the end-of-phase 2 meeting with the FDA? What's the status of the program? When will you start the phase 3 trial?
Yeah, 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 had with the FDA.
In phase 2, 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 QMGs or more severe patients, you had a better efficacy. How are you integrating those findings into the phase 3 trial?
Yeah, I mean, that, that phase 2 data, as I said, I think most investors would believe that the data was, you know, 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 scale could take 2 hours, and we were a young company doing our first trial. We wanted to make it really easy to recruit into our trial to make sure we hit our timelines. But we did a post hoc analysis, and we said: Well, what if we had had a QMG screening criteria?
Zilucoplan, the last C5 approved in MG, had 12 or higher, as well as MG-ADL 6 or higher. We did 10, like, let's say, just a little lower, make it a little easier to recruit in our trial. What if we had a 10 QMG as a minimum to recruit into the trial, as well as the MG-ADL screen 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 in complement or SC in this market. So, we believe by having a QMG screening criteria as well as the MG, MG-ADL screening criteria, we'll be able to better control for placebo.
We've learned a lot from this phase 2 trial, and we'll implement that in phase 3. So I believe now our TPP doesn't say equal efficacy to C5s; 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 2, where we took placebo patients, and when we switched them to open label clasiprubart, we didn't give them a loading dose, and that was done on purpose to give them one shot every two weeks and watch the PK levels accumulate slowly and see what happens to their MG-ADL and QMG. And we saw that just after two doses, where they achieve a PK level on average, that's half of what you achieve dosing every two weeks.
With an eight-week half-life linear PK, that means basically the same PK level we'd achieve if we dosed every four weeks.
Mm-hmm.
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 to some duration data, which shows that only 75% inhibition got you, you know, pretty good, robust efficacy, there's no reason for us to not test every four weeks. And I am fully confident that every four 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 gonna be—have a box warning. They're all C5s, potentially better efficacy-
Just one-
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 comes there in conversations with investors like, you know. And there was recently a report from FAERS 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?
Yeah, look, the FAERS database, anybody can go on there and report anything. So, sutimlimab, after 4 years in the market, a consumer put in a report, it wasn't a healthcare professional. It says it was off label. It was, you know, the dose was not what they recommend on the label either, and then it lists a whole bunch of conditions, and then the, in there, they mention 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 mention SLE. Soliris, a C5, I don't think that people believe that that has, like, 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 healthcare professional.
So all I'm gonna say is for sutimlimab, riliprubart, us, in 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." By the way, if that ever happened, we'll know it will be very rare.
Yeah.
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.
Got it. 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, or how you are sort of, modeling it internally?
Yeah. So, we haven't gone into forecasts 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 under-penetrated. This market is maybe a $5 billion market in the U.S. alone. It should be a $20-$25 billion market. So when I look at the potential for something like, you know, complement and FcRns are gonna be two mechanism actions are gonna be, you know, the first line, each other's first switch for many years to come. A very conservative market share assumption for us, let's say 5%-10% share.
Is that fair? We're gonna be the only complement inhibitor with no box warning and an auto-injector, and every two or four weeks, I think it might be every four weeks. If you just assume a 5%-10% market share of the MG market, and we're at $400,000 a year, that's right there, a $2-$4 billion drug in MG alone. If we are the standard of care and more efficacious than IVIG than in CIDP, again, and, and maybe potentially double the price-
I see.
If that's once every two weeks versus once every four weeks in MG, so it's twice as many injections for us, per year, but still an advantage over empasiprubart and riliprubart. Is 5%-10% market potential there fair? Again, that's maybe $700,000-$800,000 a year. I mean, you can do the math. It's, it's $ billions in CIDP. And in MMN, which is the smallest of the markets, 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 clasiprubart peak sales getting above $5 billion over the long run.
Very good. Final question. Ryan, how is the financial health, the bond 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 clasiprubart. This year, as it relates to the CIDP interim responder and the phase 2 MMN data, the second half of this year, and also allows us to read out the milestones for DNTH212 with the phase 1 healthy volunteer SAD data this year, and then some SLE data next year as well.
Perfect. Thank you, gentlemen.