For the reimbursement meeting. We're on.
All right, we're on. Thanks for joining in, everyone. Next up we have Marino Garcia, who is the CEO of Dianthus Therapeutics. Marino, over to you for an overview of the company, where things stand. It was a big year this year. I'll let you kind of open it up, and then we'll go into Q&A after that.
Sure. Before I start, though, thank you to you and Evercore for the invitation to participate in your conference here in beautiful Miami during a very, very tough Northeast weather system. Anyway, yeah, so it has been a big year. I think the way I would set this up is to say I think in a lot of investors' eyes as well, Dianthus feels like a significantly de-risked company right now. The MG data that we presented, phase II data back in September, confirmed the potency and that we have the right dosing for neuromuscular conditions with 300 mg every two weeks. C onfirmed the safety profile of an active C1s inhibitor and claseprubart specifically. It was kind of seen as a bit of a clearing event for us, because now we continue to execute and we're now facing two very important catalysts next year.
One is the interim responder analysis with CIDP, which we can get into if you like, in the second quarter of 2026. And then in the second half of 2026, our phase II top line data from our MMN trial. And those two indications already have proof of concept without other classical pathway or active C1s inhibitors. So, it does feel like now we're all about execution. We did bring in a new asset, the NTH 212, a new bispecific or bifunctional fusion protein. We licensed in from China. That could be a is a first in class, best in class potential, and also a pipeline and a product, which we can talk about as well. So yeah, it really is a very different company and it's very proud of what the team's achieved this year.
Awesome. All right, so let's dive right into the CIDP side to start things off.
Sure.
Before going into the trial design, I've gotten this question a couple of times. Moving the timelines up to 2Q, is that solely due to quicker enrollment or is it partially due to like a high responder rate that you're seeing that kind of builds confidence?
So, to be clear, I'm not seeing any responder rate. I'm not seeing any data. That's a very small number of people in the company that are seeing that, obviously doing that very consciously. Now, that was, purely from, accelerated, recruitment. Specifically, from the moment we had the MG data and we presented that data to our investigators, anecdotally we heard from some CIDP investigators that that really gave them a lot of encouragement that, this, this anybody was, that anybody was doing what it was supposed to do at every two week dosing. And the safety profile was very reassuring. So we literally saw, recruitment accelerate like a hockey stick post MG data. The reason we were able to accelerate our timelines and our competitors actually went the other direction and delayed theirs. And this was a very conscious decision. We designed our phase III trial.
We modeled it after the ADHERE trial from argenx. Because A, it's a very attractive, high probability success trial. And attractive meaning, it's, it becomes very attractive for investigators to participate in and patients to enter because of that open-label part A. And we made it even more attractive because we made a couple of important changes to the trial compared to ADHERE, which I can get into if you like. But the other CIDP trials, for example, Sanofi's riliprubart, you don't know as a patient if you're going to be getting placebo or active drug, and you don't even know if even if you get active drug, if you're actually going to respond to it. That's a typical blinded right from the start randomized trial, placebo-controlled trial.
For us, you're getting open label drug right off the top, and only if you respond do we then randomize you into part B. And so plus we make patients only having to come in every two weeks versus riliprubart, you have to come in every week to get two shots. So I think it's just clear why we have a much more attractive trial. And investigators tell us that it is the, you know, the preferred trial to participate in.
Awesome. All right. So one of the key differences, which I'm sure you'll go into, is the lack of the washout.
Yes.
Before going into part A.
Yes.
So I guess two of the questions there are like, number one, how are you confident you're confirming the CIDP diagnosis?
Yes.
Number two, doesn't this just mean inherently with a lower baseline?
Yep.
That you'll have a lower responder rate in the study?
So let's be clear. There is, I don't see any future trials in CIDP doing that again, making patients relapse. Investigators will tell you very clearly, they're not doing that anymore. That is cruel. It's not needed. The way we confirm diagnosis is physicians are becoming much more comfortable diagnosing CIDP, but we also have an independent review board of experts that review every case and confirm whether the patient has CIDP or not. And if they confirm it, then we, you know, it's a dual authentication system. So the patient can go into the trial. Let me remind people, the p hase II riliprubart data was open label, just like our part A. They did not make patients relapse either. They had everybody switch within a week from IVIg. That's what we're doing. That was really impressive data.
So impressive that it gave Sanofi the confidence to go and do a head-to-head trial versus IVIg. Nobody does a head-to-head trial in any therapeutic area versus the gold standard efficacy treatment unless you think you're going to win. But it's not just Sanofi that has that confidence based on their own phase II data. It's our genetics. Our genetics has two therapies in CIDP, one approved, efgartigimod, and the other in development, their C2 inhibitor empasiprubart. But only one of those two therapies is doing a head-to-head trial versus IVIg. And it's their C2 inhibitor. And it's based off the really impressive data riliprubart demonstrated in their phase II open label trial in CIDP. So their trial did not make patients relapse. They made patients switch right away.
So when you see that 50% responder rate for the standard of care refractory or standard of care stable patients, think about that. That 50% responder rate of 50% patients getting that additional one point on the INCAT score improvement, that was over whatever IVIg was doing before, because they weren't made to relapse, right? They were just switched immediately. And that is one thing I would caution. You cannot compare whatever we have in part A to what ADHERE had in part A, because ADHERE made, removed the IVIg, made patients relapse, and only those that relapsed did they then put in an active drug in part A. And only 2/3 of those patients got back to where they were with IVIg. That means a third of patients weren't even able to get back to baseline. Think about that.
With riliprubart, not only do you not make them relapse, you switch immediately within one week when their next IVIg dose is very likely due anyway. You put them on active C1s inhibitor and 50% of patients got even better than what they were doing with IVIg. That increased efficacy signal is what gave argenx and Sanofi the confidence to do a head-to-head trial versus IVIg. One additional point, another difference between our two-part phase III trial in CIDP versus ADHERE is that we do allow patients who are refractory to IVIg into our trial. No FcRn will study refractory patients to IVIg. Why? Because FcRns are seen as less effective than IVIg. If IVIg didn't work, it's very unlikely FcRn will not work.
Where could FcRn work if a patient is tried on IVIg and it seems to work, but the tolerability is really like not acceptable? If the dose administration is not acceptable, if FcRn is a logical next step because maybe they'll respond to it and it's definitely a more patient-friendly version of IVIg, but it's less effective. That is clear. So we do allow refractory patients because again, riliprubart's data, they allowed refractory patients to enter into their trial, switched right away, and 50% of those patients improved. That's a really strong efficacy signal from active C1s inhibition. So two big differences. So what we're looking for in our part A interim responder is we want to see efficacy that tells us that we are similar at least to riliprubart's efficacy, that we're competitive.
And then we let our dosing administration advantage of one shot every two weeks instead of two shots every week be the differentiator there.
Awesome. All right. So for the interim analysis, are you planning to actually share the part A responder rate? It's, you know, it is a single ongoing registrational study. ADHERE did not show theirs, theirs for this reason. Are you planning to show the rate or give some type of other update?
Yeah, it's going to be very difficult. I would love to. Obviously, look, if it's a go, people should take away that we're seeing efficacy that's competitive to riliprubart. Maybe better, but at least competitive or similar. The FDA is very clear. They do not want you to reveal anything else. And we need to be very careful. It's a single registrational trial. We do not want to do anything that calls into question the integrity of the trial. So it'll be very difficult to show more, but we're looking into what could we do other than just say it's a go. And let's be clear, in my mind, there's no no-go scenario. Like it should work. Classical pathway inhibition is proving to work in CIDP. It's more go or do we need to make some change?
The only change I can really imagine that would be based on any data we're seeing is that maybe we have to dose once a week. I just don't see it. We clearly showed in MG that every two week dosing is very potent and we expect to see the same. And frankly, with our one shot every two weeks versus two shots every week with riliprubart, which is what they had in their phase II and continue to have in their phase III, we're getting more significant inhibition of the classical pathway than they are, even at, you know, four times less a dose. So, I just don't see that scenario playing out. So a go should be taken as we're seeing at least similar efficacy to what riliprubart demonstrated in phase II.
It's like, just to be clear, there is a hypothetical scenario where there is a no-go. Like if you do 5% responder rate, for example, that's probably not a trial change. Like it's.
Yeah, yeah. And then that would tell us like something about the riliprubart data in phase II didn't somehow get replicated with a more potent active C1s inhibitor. So it's very unlikely, but yes, it's biotech. So it's never zero risk.
Yeah. Okay. I agree it's not likely, but that's the point is if there is a no-go scenario, passing to a go is a good outcome. It's not like, it's not like, hey, we saw 5%, but we're going ahead like the next scenario. Okay.
At that point, it would be maybe we need to do one shot a week.
Yeah. Okay.
And we'd still be half the number of shots as riliprubart.
That makes sense. I, I guess there's also a concept of saying, hey, the data met our bar versus exceeded our bar. Are you able to say something like that?
So the question really in CIDP is by getting higher levels of inhibition of the classical pathway, like we believe we get with our dose versus the riliprubart, do you see more efficacy in CIDP? We don't know. We don't know if we're both already maximizing efficacy or if there's still more efficacy you can gain. Look, that the kind of response rates riliprubart had in their phase II is pretty impressive. Impressive enough, like I said, that two companies are doing head-to-head trials versus IVIg. The only reason you would do that is if you think you're going to win. I do not want to set an expectation we'll see better efficacy, but it's a question that nobody's answered. My expectation is we will have similar efficacy with one quarter of the dose, one quarter of the number of injections.
Yeah. I guess one more question on part A, and I actually think part B is what matters way more when you look at the randomized withdrawal and the hazard ratio. So, but I just have to ask the part A because that's kind of the next year question.
Sure. Yeah.
Lost my train of thought.
Maybe what are the odds that we're going to be go or what?
Yeah, I was going to say more like, what is your bar internally? You've mentioned 50% probably four times in this conversation.
Let's be clear. Riliprubart, depending on different points they cut the data, they had anywhere from 40% to 50%.
Yeah.
Response rates. This is just looking at the first 40 patients. If we're somewhere in that 40%-50% range, we know we have a competitive drug, so my point is we're not going to proceed with that once every two-week dosing if somehow it looks inferior, and that, that would be the only scenario where we make a change, so it's not like, when I say it's not a no-go, it's, it's a go, but we change the dose. I think it's very unlikely. I think it's going to be a go, and once every two-week dosing, we already know gets significant levels of inhibition of the classical pathway and there's no need to get more inhibition. I don't think in a neuromuscular condition.
What about on the other end of the spectrum rather than adding another dose? What about removing one of the higher doses? Like what we saw in MG, right? Super potent potential even for monthly dosing. You've alluded to this in the OLE. Why could some of this not also be true in CIDP?
Look, I'm very clear about why we ever even added a 600 mg and it was dosed into any of our programs. And it was because it was clear investors just wanted to have a higher dose, a second shot on goal, if you like, just, you know, have at least two doses in our first trials. We always said we did not expect 600 mg to provide any additional efficacy. We did not expect 600 mg to really provide any additional benefit over 300 mg every two weeks. Once we see our first 40 patients, if we are hitting the efficacy numbers we expect, then we'll look at that 600 mg again. Again, if somehow we need to go to once a week dosing, that's what the 600 mg every two weeks is really.
We have a 60-day half-life to PK of 300 mg once a week or 600 mg every two weeks is the same. So if somehow we also have to change part A to 300 mg once a week, well, the 600 mg in the second part is exactly the same dose. So those two doses are there until we see what the first 40 patients are and then we'll look at them again.
Awesome. All right. That makes sense. Are you measuring ANA titers in the CIDP study?
We are, but like we're going to do for phase III MG, we're going to talk to the FDA about removing it. It's just a burden and it's not telling us anything. So, much like riliprubart got rid of, you know, a lot of the ANA testing in their phase III programs, both their trials for CIDP, we're going to do the same for MG and we're going to do that for the rest of our program as well. Now that we know it doesn't tell us anything.
Yeah. Is that the same conversation as the MG end of phase II?
Yeah, that'll be part of it. Yeah.
Okay. And that'll be specifically part of it for CIDP?
Yeah.
Okay. Awesome. Let's actually go to MG before coming back to MMN. On the potential for every four-week dosing, I mean, you've laid out a lot of the OLE data. Do you think there's any more full exposure response analyses, PK/PD, that'll kind of help us inform every four-week dosing potential?
Not really. I mean, look, there's three bits of evidence, right? One is when you have 300 mg and 600 mg every two weeks and you see no dose response, you know that you're at the top end of the efficacy curve and you haven't found your minimally effective dose. The responsible thing is if you can, you test the lower dose in the next trial. Two, our open label data clearly shows that at PK levels, half of what we achieve with 300 mg every two weeks. So we get about 100 μg and 120 μg per mL at 300 mg every two weeks. 300 mg every four weeks will be about half of that. That we're seeing a significant drop on the MG-ADL as well as the QMG after already a very significant drop during the first 13 weeks on placebo. That's really significant.
We always designed the trial that way to look at that, in the open label. That's why those patients don't get a loading dose. We wanted to see the PK levels slowly accumulate and track their scores. And then finally, Regeneron in August put out a press release for a C5 inhibitor in MG where they had very good efficacy, it looks like, a 2.3 versus a placebo on the MG-ADL. And the only other information they released is that they achieved only 75% inhibition of the classical pathway. That's the first time that any complement inhibitor has been shown that you don't need to be anywhere near the IC90. We dose every two weeks because we want it to be above the IC90 just to reassure investors that we would have efficacy in our trial.
Our every four-week dosing will be very similar to cemdisiran or better. There's more and more data accumulating from our own trial as well as external validation that there's no need to accumulate that much drug. So, I fully expect Q4 week and Q2 week will be very similar in efficacy and that Q4 week may end up being our dose as we launch into MG assuming we get approved.
Awesome. All right. Going to the MMN side of things quickly.
Yeah.
How are patients confirmed to be IVIg responsive or dependent? Like, do they go off IVIg in the trial?
Yeah.
Okay.
If they're on IVIg and they're retested, so it's a long screening. It's a difficult trial to recruit into it. There's a long, long screening period. We're following the model from the argenx phase II trial, so but we still expect to have our top-line results in the second half of next year for that, for that trial.
Awesome. Anything you can say on the baseline of patients that have been coming in? Like, is it generally similar to what we saw for empasiprubart with a rgenx?
There shouldn't be any significant difference, but we're not disclosing yet any of the baseline characteristics or what we're seeing in that trial yet.
That makes sense. I guess looking at different clinical measures too, argenx is using grip strength in their phase III . I guess there's also time to IVIg or treatment, RODS, a whole host of measures.
Sure.
What do you think matters most?
Clearly grip strength seems to be the primary endpoint, and I'm assuming it's in conversation with the FDA. When we went to the FDA for our phase II MMN trial, they clearly told us you're going to have to come back to talk about the phase III and what will be the primary endpoint there because we're not sure yet. So the nice thing for us is that you know, hopefully that's what argenx and the FDA are figuring out and then it'll be much clearer for when we go to have that conversation with them, and we should see their phase III results before we have to make our final decision on our phase III design, so we'll learn from their results and then apply those learnings to our phase III.
Perfect. One quick question on 212 since we're essentially just out of time, and I know we'll be talking about it more next year anyways.
Sure.
Just on timing of the indication selection disclosure, is that planning to come before you show the phase I data in the second half of next year?
Yes.
Okay.
Yes.
Awesome. So we'll talk more about that next year.
Awesome. Thank you.
All right. Wrap it up. Thanks everyone.