Good. Hi, everyone. My name is Maury Raycroft. I'm one of the biotech analysts at Jefferies. It's with great pleasure that I'd like to welcome the CEO of Dianthus Therapeutics, Marino Garcia. Dianthus had an update today. There's some new data, and there's a slide deck which is actually pretty interesting comparing their drug versus riliprubart Sanofi's antibody. Without further ado, I'll pass it over to Marino to tell you more about the company. I think we'll do a few questions for Q&A afterwards. Thanks for joining us.
Thank you, Maury. Thank you to the Jefferies team for this opportunity to provide an update on all the great progress the team's making with our lead program DNTH103 over at Dianthus. Why don't I just jump in? Just a reminder that I will be making some forward-looking statements. So I please refer you to our website and our SEC filings for more information and all the risks pertinent to our business. Just an introduction, Dianthus Therapeutics was formed in 2019 to develop what we're calling next-generation complement therapies to treat severe autoimmune diseases. Our lead program, the DNTH103, is a perfect example of what we mean by next generation. It's a very potent investigational monoclonal antibody that targets the classical pathway only by selectively inhibiting only the active form of the C1s protein.
The idea here, the intention, is to be the very first self-administered subcutaneous injection that could be put into an autoinjector, and patients can self-administer as infrequently as once every two weeks for conditions like myasthenia gravis, our first beachhead indication. We have top-line Phase I data that confirms that we have a nice extended 60-day half-life thanks to the YTE modification, that we have a very potent classical pathway inhibitor, and that potentially we could have a differentiated safety profile. There's now clinical proof of concept in the three indications that we are targeting in neuromuscular indication and not in the autoimmune space. That proof of concept has been demonstrated in myasthenia gravis, our first indication I mentioned earlier, CIDP and MMN, and I'll talk a little bit about those in a moment, which validate that pipeline and our molecule potential of the DNTH103.
We've initiated our first Phase II, myasthenia gravis, back in the Q1. We intend to have pipeline results from that trial in the second half of 2025. Very soon, we'll provide an update on the initiation of our Phase II program in MMN and later this year in CIDP. Finally, we have a cash runway that takes us out to the second half of 2027. The DNTH103, as I mentioned, offers that very exciting pipeline within a molecule with its best-in-class properties. We're going after multiple neuromuscular indications where there's clear clinical development and commercial synergies, and where the DNTH103's potentially best-in-class properties could really offer a significant benefit for all these patients. There's first one, the priority, as I mentioned, our first indication, our beachhead indication, that's generalized myasthenia gravis.
This is a multi-billion dollar market dominated by IV first-line biologic treatments where there's still a significant need for better improved therapies. That's where we have our Phase II program already going on, and I'll talk a little more about that later. Then there's CIDP. This is a very exciting indication where we now have proof of concept for an active C1s inhibitor in terms of efficacy and CIDP. And that's from Sanofi's active C1s inhibitor, riliprubart, which demonstrated really impressive efficacy in CIDP. And I'll talk a little bit more about that in a moment. We also, as Maury mentioned, have new data that we've just started revealing today, or I'll talk a little bit about in a moment, that clearly show that 103 is superior in terms of its affinity for active C1s as well as its pharmacodynamic potency versus riliprubart.
And then finally, in MMN, earlier this year, J.P. Morgan, argenx, revealed some very impressive data for their C2 inhibitor, an IV complement therapy for MMN, where again, pretty much validates the mechanism of action in terms of classical pathway inhibition for this condition. I'll talk a little bit more about that also. First was generalized myasthenia gravis. As I mentioned, this is a multi-billion dollar market that's dominated by two first-line biologic classes, but each with significant room for improvement. First is the complement class dominated by C5s. They're selling over $6 billion a year and still growing year-over-year. That growth is coming from mostly myasthenia gravis, especially in the U.S. with first-line use in treatment-naive patients. It's pretty much all IV.
So if you can deliver similar efficacy to these, but with a safer profile, with a more convenient profile, that's a huge opportunity to be a best-in-class complement inhibitor. And then, of course, the FcRns, some of you are probably familiar with the tremendous success VYVGART has been for argenx, just speaks to the hunger for new mechanisms of action in this market. They're obviously already achieved blockbuster status. Most of those sales, again, also being IV on a weekly basis with treatment interruptions that risk relapse. So again, still a potential benefit for something like 103 to benefit these patients. CIDP, as I mentioned, very exciting developments. Recently at AAN, Sanofi presented interim data from their Phase II CIDP trial with riliprubart, their active C1s inhibitor. And they showed impressive efficacy in 3 different types of patients in CIDP.
One is patients who are treatment naive to IVIG standard of care. They saw 75% improvement. Another is patients who are refractory to IVIG standard of care. There, they saw 50% improvement on their active C1s inhibitor. And finally, really interesting is patients who are stable, doing fine on standard of care IVIG, 88% of those who were switched active C1s inhibitor, 88% of them remained stable or improved. Actually, half of those, 44% patients, actually improved even though they were already doing well on IVIG standard of care. It's a very interesting efficacy signal they provided. This has caused a lot of excitement. It's the first time an active C1s inhibitor has been shown to work in any disease. It's the first time a complement inhibitor has been shown to work in CIDP, an area with very high unmet need.
The key differentiation between riliprubart and 103, their maintenance dosing is 600 mg every week. That's 4 milliliters. So if you think of it as an autoinjector, that would be 2 autoinjectors every week. Our maintenance dose target dose for 103 is one 2 milliliter, 300 milligram shot, one autoinjector every two weeks. So potentially, it could be the difference between 8 injections every month versus 2 injections. What gives us the confidence that we can have that level of differentiation versus riliprubart? And this is the new data. We conducted 6 different experiments, 6 different assay experiments, in vitro, head-to-head, similar protocols, similar reagents in a controlled setting. And it clearly demonstrates that 103 has superior affinity and pharmacodynamic potency versus riliprubart. The first 2 on the upper left are the affinity assays.
Here we did the SPR, very well-known method, and also KinExA, which is a little more sensitive for low-picomolar affinity tests like this. What we see is a 4- to 8-fold improvement in affinity for 103 versus riliprubart. We conducted a Western blot test, an enzymatic assay, head-to-head to see how effective they were at blocking the cleavage of C4, a substrate of C1s, to then prevent the cascade, the complement cascade, which eventually leads to the formation of the MAC. There again, we saw 8 times more potent, 8 times more potent at blocking the cleavage of C4. Finally, we conducted 3 head-to-head in vitro assay experiments, functional assays, looking at what levels of drug do you need to get to inhibit 90% of the complement pathway.
What's most relevant to us, frankly, is the CH50 hemolytic assay, which you see there highlighted in the middle. That's the assay, the gold standard for complement therapies to determine what dosing do you need to, what levels do you need to get to, what dosing do you need to administer to get above 90% inhibition of the classical pathway. And there we saw that we were 7 times more potent than riliprubart. We also conducted 2 other assays, Wies lab, liposomal, just to see what it looks like. Same thing. We saw anywhere from 3-12 times more potency, the pharmacodynamic potency versus riliprubart. So no matter how you look at it, across all these different assays, across all these head-to-head in vitro experiments, it is clear that 103 has a higher affinity and is a more powerful, has a stronger pharmacodynamic potency than riliprubart.
That's what gives us the confidence that we could see exciting efficacy with lower volume, more convenient dosing and administration for patients. Then finally, as I mentioned with MMN, our argenx presented some data earlier this year with a C2 inhibitor. It's very clear, they state in their own paper, that this is all driven by inhibition of the classical pathway. And so this is another proof of concept for classical pathway inhibition in another disease, and this time MMN. What's exciting about MMN is sometimes it is a smaller of the three indications, but it's one where FcRns do not work. This is complement-only market. And right now, there's only two complement inhibitors being studied in MMN. That's empasiprubart, the C2 inhibitor, that's an IV from argenx, and 103, which we will have news imminently on.
The issue is there, again, an IV every week, every two weeks, not terribly convenient for patients, but also it's a C2 inhibitor. That means it doesn't just block the classical pathway. It also blocks the lectin pathway. And that potentially could lead to the increased risk of infections from encapsulated bacteria. There is only one complement inhibitor on the market that's approved without a box warning around any safety issue, including infections. And that's sutimlimab, Enjaymo. It's a C1s inhibitor. Every other complement inhibitor, whether it's C5, C3, alternative pathway inhibitor, they all have box warnings with REMS programs around the risk of encapsulated bacteria and infections such as meningitis. So again, we believe we have a better antibody, and we look forward to seeing their final results sometime in the near future. So this is a year of execution for Dianthus on 103.
We've kicked off the myasthenia gravis program in the Q1. We expect to see data from that in the second half of 2025. We'll have news imminently on MMN and kicking off that Phase II program. Later this year, we'll also have an update on the start of our CIDP program for 103. Now, just to dig a little bit more into that beachhead indication and myasthenia gravis, as I mentioned, it's a tremendous 60,000 patients in the U.S., already supporting multiple multi-billion dollar blockbusters and growing every year. If you look at the marketed and approved therapies today, you can see that there's nothing that delivers that kind of convenience and reduced patient burden that 103 potentially could deliver. At the bottom, you see these are the IVs. They're approved, Ultomiris, Soliris, as well as VYVGART.
They're accounting for the vast majority of the revenues I showed you earlier. But again, they're IVs some every week or every few weeks, but still quite a burden. But we do have now some subQ therapies approved, as you can see in the middle. There's two FcRns that have to be administered by healthcare professionals, unfortunately, because they're higher volume, more complex subQ injections. And then we have, excuse me, Zilbrysq, or zilucoplan, a C5 inhibitor from UCB. Unfortunately, that's a prefilled syringe that people have to self-administer every day. So the good news is that there is now a self-administered option for patients. Unfortunately, it is an injection they have to give themselves every day. But there's nothing that on the market that looks anything like 103, where it could be a potentially self-administered autoinjector delivered as infrequently as once every two weeks.
But it's not just about patient convenience from a dosing administration profile. We know that inhibiting the classical pathway and that complement inhibitors work in MG. So our goal is to deliver similar efficacy to that gold standard complement efficacy. But it's to do it in a safer manner as well. If you look at all the complement inhibitors that are approved today for myasthenia gravis, they're all terminal inhibitors or C5 inhibitors. That means they block the formation of MAC no matter how the complement system was triggered, whether it was through the presence of, sorry, antigen-antibody complex and AChR-positive patients in MG, or whether it was by encapsulated bacteria triggering the lectin pathway. The problem is it shuts everything down. So that hence you have the black box warning and the REMS program around the risks of encapsulated bacteria and infections such as meningitis.
There is one classical pathway-only inhibitor approved on the market. That's Enjaymo, sutimlimab, first-generation C1s inhibitor. Unfortunately, you have to deliver 6.5 to 7.5 grams of antibody every two weeks through IV. But it is the first and only approved complement therapy that doesn't have any box warning around the risk of infection. Why? Because it does not touch lectin. It does not touch the alternative pathway. And those are the pathways you need to fight against the risks of infection. The classical pathway inhibition is what you need to fight against conditions like myasthenia gravis, which are what trigger the classical pathway. So it's not just about a patient convenience from dosing administration. It's potentially a safer option that we could be offering for patients with myasthenia gravis and differentiate ourselves from other complement inhibitors. Let me move now to our Phase one data.
So we now have Phase I data, as I mentioned earlier. It's 8 healthy volunteer cohorts, 4 are IV SAD cohorts, 2 MAD subQ cohorts, 300 and 600 mg summarized it here. The first graph on the left is the IV SAD cohorts. This is what pretty much confirms that we have very nice linear PK and that we have a nice healthy 60-day half-life, thanks to the YTE half-life extension that will allow us to dose infrequently. The middle graph shows that you get very nice accumulation because of that 60-day half-life. By dosing every 2 weeks, we can get to significantly high levels.
You can see the nice accumulation with every two-week dosing subQ. Then the third graph on the right, we plotted every single healthy volunteer at every single data point from every single cohort and mapped out the PK/PD curves data points. What that tells us is that with DNTH103, we inhibit 90% of the classical pathway. We get to IC90, as measured by the CH50 hemolytic assay, that gold standard assay I mentioned earlier, at 87 mcg per mL. We took all that data and we modeled it out. What we know is if we dose after a short loading dose, if we dose 103 every two weeks with one 2 mL, 300 mg subQ shot, we will hover between 125-115 mcg per mL. On average, about 120 mcg per mL.
As you see on the dashed line, that's the IC90. We get about 40% above that level. We have a nice healthy margin above the IC90 dosing 300 mg every two weeks. That's what gives us the confidence that we can see efficacy across these conditions with one single shot, one self-administered autoinjector every two weeks. The safety profile, it's a very favorable clean safety profile. We have no serious adverse events, no grade three, four adverse events, no infections related to the complement system. Two patients had injection site reactions that were mild. They're in the MAD cohorts and they still finished their doses. So that's two out of 60. So it looks really, really good. We had two patients that did switch from, sorry, healthy volunteers that switched from ANA negative to ANA positive at day 57. Both were tested for double-stranded DNA and were negative.
Both were not diagnosed with any autoimmune disorder and both were fine in follow-up. So again, a really, really generally well tolerated and favorable safety profile for 103. So as I mentioned, we are now kicked off on our Phase II program with MG having started. The key point here is we have 2 doses we're testing versus placebo. As I keep saying, 300 mg every 2 weeks is our target dose. That gets us above IC90. That's very strong inhibition of the classical pathway. And we're confident that dose will max out efficacy. But just in case, to answer the questions, what happens if you get above IC95 with an upstream inhibitor like DNTH 103? What happens if you double the dose for such a potent antibody? So we decide to throw in 600 mg as a dose.
We're going to find out, is there any additional efficacy by going even higher in terms of the levels of inhibition of the classical pathway? And it's also a good insurance arm. So I'm really eager to see the data for these two arms. That 600 mg gets us to about 240 mcg per mL steady state. Our IC95, as you can see in the footnote, is about 149 mcg per mL. So way above the IC95. This is, that is a very strong dose. It's a 12-week study, by the way. And assuming it's positive, the Phase III study will be identical, just larger numbers. Maybe only one active arm, maybe two. So in summary, with a couple of minutes left for Q&A, this is, the team is just fantastic. They're executing on all fronts. It really is a very exciting time.
We're finally getting the ability to have patients try 103. We've started with MG. We'll have those results for the second half of 2025. I hope by sometime late this year, maybe, well, by JP Morgan for sure, is provide an update on how we're doing with recruitment and be able to fine-tune when exactly we'll see top-line data. But right now, we're saying second half of 2025. We're imminently going to have news on MMN. And then second half of this year, we'll provide an update on our CIDP program. There are a few other interesting milestones that we should be seeing from our external catalysts. I think I mentioned, we'll see the final results of the Sanofi Phase II riliprubart data. The data I showed you earlier was interim data.
And hopefully, we'll see final results from the Phase II empasiprubart, or C2 inhibitor, from argenx and MMN at some point later this year. And both of those will, again, I believe, continue to build confidence around this mechanism of action in these disease states. Finally, we wrapped up our Q1 announced. We had about $377 million in cash. And that takes us out to a runway out to 2027, second half of 2027. With that, thank you for your attention. I'll take any questions now.
Great. Thanks, Marino. Great presentation. And congrats on the new data that's in the slide. Maybe I'll start there. If you can just talk about the robustness of running the multiple assays. And on the slide, it mentions that some of the assays were confirmed at independent labs.
I don't know if you can comment more on what was done in-house, what was done outside, and start with that.
Yeah. So except for the affinity assays, everything else was experiments, the average for multiple experiments we did in-house. For a few of them, we did have independent laboratories do it just to do a double check, just to make sure that we were, you know, what they see is consistent with what we're seeing. And it was. But, you know, for example, for the three functional assays and most importantly, for the CH50 hemolytic assay, we repeated that three times. And what you're seeing is the average number from those three assay experiments.
Got it. And this, so you've got the YTE modification in the antibody. These assays have nothing to do with that. There've been debates around potency. And so with these experiments, you're showing that you're more potent than Sanofi's antibody. What makes the difference in potency? I guess, can you talk more about that? I'm guessing it has something to do with the epitope that they are binding to.
Right. Yeah. And it's something we may, we'll publish more of this information in the future, and we'll put it into a manuscript and provide a little more detail around that. But yeah, they're very different in the way they're binding to the epitope or how they're blocking the cleavage of C4. Yeah. So that's all I can say for now about that. Sorry, your question at the beginning, you had something.
That was it. Basically, just the primary difference that we're seeing here, it's due to the.
Right. So I want to be clear. There's clear difference in terms of affinity to active C1s. And then the difference in potency is really in the pharmacodynamic. These are in vitro experiments. We don't have access to, we don't know what their CH50 IC90 is. It's never been published as far as we know in any publication. It's not part of their Phase one publication. So these are all done on a dish artificially. All I can say is for our IC90 on the CH50 hemolytic assay, we got 98. It's very close to the 87 we saw in humans. It's pretty much the same. So for us, it tells us that for our antibody, it seems to be pretty accurate. We don't know what Sanofi's data is from there. They've never really reported it.
Got it. When could we learn more about 103 then and what's driving that difference? You said you could potentially publish something on that.
Yeah. We'll be working on putting all this together into some sort of manuscript in the future and publish it at some point. But this is all we've got right now.
Got it. Okay. And also wanted to ask just on the MG study, if there's any additional status update you could say there on site activation and enrollment on the?
All I can say is I'm very happy with the progress we're making, but we're not providing updates on an ongoing basis. As I said, my hope is to provide an update toward the end of the year or J.P. Morgan at the latest and then fine-tune when exactly we'll see data.
Got it. Yeah, I'll finish up there.
Sure.
Okay.
You have one more?
Well, I was going to ask one more just with the competitor catalysts. Anything specific that you're going to be looking out for as it relates to Dianthus?
I think for Sanofi, it'll just be more of the same data. I'm not really looking for much more on that active C1s inhibitor. For the C2 inhibitor from argenx, I'm eager to see the PK/PD relationship, what level of inhibition are they achieving using a CH50 hemolytic assay, for example, to achieve whatever efficacy they report. I think that'll tell us a little bit about their potency. And then we'll be able to say, okay, so do we expect to see similar efficacy, better efficacy? How does our potency compare to theirs? That's data we don't have for them.