Conference Transcript - DNTH 2026-11-09

Yatin Suneja, Analyst — Guggenheim

Okay. Good morning, everyone. Welcome to Guggenheim Third Annual Healthcare Innovation Conference. My name is Yatin Suneja, one of the senior biotech analysts here at the firm. It is my pleasure to welcome our next presenting company, Dianthus. From the company we have President and Chief Executive Officer, Marino Garcia. Marino, I see you've prepared a few slides. Why don't you walk us through these slides, maybe give us an update, and then we'll go into sort of a Q&A.

Marino Garcia, CEO

Sure. Thank you, Jan, and thank you to the Guga9 team for this opportunity to be here with you today. So just quickly, I'm going to be making some forward-looking statements, so please, I'll refer you to our website and our SAC filings for all the appropriate risks, etc. So just very quickly on Claspirobar, I'll just focus on our lead program, our active, very potent active C1S inhibitor. Our goal with Claspirobar is to achieve a target product profile at approval that positions it as a first-line treatment across mycenogravis, CIDP, and MMN. The way we'll do that, we're aiming for best in disease efficacy. We're targeting very rapid, sustained, consistent efficacy. And I'll talk a little bit in a moment why we believe we may have best-in-disease efficacy with Closhipobard. Secondly, differentiated safety will be the only classical pathway inhibitor or complement inhibitor with no box warning and REMS program. And finally, that patient-friendly Dupixent-like auto-injector. I urge you to understand how simple it is. Go to the Dupixent website, watch the patient video. Literally a five-second, super-fast auto-injector that patients can easily self-administer once a month in MG, once every two weeks in CIDP and MMN. And then finally, with these three markets in the United States, it's about 150,000 total patients. We still put opportunity to grow with the appropriate biologic that could be used earlier in more active, less severe patients. Right now, for example, the myasthenogravis market, patient population in the United States, despite having a decade now of complement inhibitors and FCRNs available, still less than 20% of myasthenogravis patients are on biologics. Why? Because you don't have the ideal biologic. That rapid, consistent efficacy, no box warning, with the super convenience of the SHL Moly auto-injector, which is exactly what Dupixent uses. Why do we say we think we could have the potential for best-in-disease efficacy? This is a slide to summarize three elements. One, on the left, C5 inhibitors shut down the complement system. They shut down the complement system whether the classical pathway was triggered or the lectin pathway was triggered by encapsulated bacteria. They shut down everything. So that's why they have box warnings and REMS programs. The one thing they cannot do is prevent the formation of C3A and C3B, because that happens upstream of C5. We work upstream of C3. C3A and C3B are toxic split products. They are pro-inflammatory. In MG patients, C5s are doing nothing about this. We will prevent this. This may give us additional efficacy in MG over C5s. The reason we work in CIDP and MMN is because we prevent C3A and C3B deposition. C5s don't. The middle graph is a reminder of our potency difference versus Rilipibart. The active C1S inhibitor is still being studied in one of the two phase three studies. They failed on one of them, but the other one passed futility and is still ongoing. We are seven times more potent at the IC90 using CH15-melodic acid than Rilipibart. This is why in our part A, we're seeing much higher response rates. Than they saw in their phase 2 open label study. They had about a 50% responder rate in their phase 2. We are seeing 75% responder rates in our first 40 patient interim responder analysis. We just put out an update. That we don't think we'll even need 200 patients in Part A in order to recruit 128 patients into Part B. That is a very clear signal that those high responder rates we saw on the first 40 patients are sustained now with more than double the number of patients having gone through Part A. And finally, on the right... As an even more dramatic difference in terms of potency versus M-pacipibart. There, at the IC90, using the Cadell Microview CH50 assay, the assay they published with to highlight their potency as a classical pathway inhibitor, we are 38 times more potent at the IC90. So even more dramatic of a difference in terms of potency. There is no more powerful, potent classical pathway inhibitor than clacipibart in development. These are the data that give us confidence, including our Part A 75% responder rate we saw with our interim responder, the first 40 patients, are what give us confidence that we will have best in disease efficacy across all three indications. Now, focusing on Momentum or our MMN Phase 2 trial that's coming up in December, a reminder, this is a very small study. If the FDA and we had known what a Phase 3 could look like in MM, we would have probably gone straight into a Phase 3. But at the time, there was no precedent. Nobody knew what a Phase 3 would look like. Nobody knew what the primary endpoint should be. So we went ahead and did a small proof of concept in Phase 2. This is a safety study. We have some efficacy measures, of course, in terms of muscle strength as secondary endpoints. We have over-enrolled, we were targeting 12 patients. It's going to be about 15 patients per arm. We're over-enrolled, and we have 46 patients who have completed the study, and we expect the results in December. A reminder, we do have two arms, 300 milligrams and 600 milligrams. We do not expect to see an efficacy difference between those two, just like we didn't see it in MG. And of course, a placebo arm. One big difference between the two trials, I really need everybody to understand, Argenix made a big deal about the 91% reduction in need for IVIG rescue in phase two. That endpoint is gone now. It's not even in phase three. It is irrelevant. We both decided how which patients get IVIG rescue in very different ways. They had patients who had clinical deterioration and didn't get IVIG. They had patients who didn't have clinical deterioration and got IVIG because they allowed for a patient to raise their hand and ask for IVIG and they gave it to them. Despite having no evidence of actually deteriorating clinically. In our trial, a patient gets IVIG only and when they have clinical deterioration documented, period. There's no asking for IVIG, and you get it even though you don't have clinical deterioration. And if you have clinical deterioration, you get IVIG. So very, very different. It's really an irrelevant endpoint. I understand why they wanted to make a big noise with 91%, but it's not even something to look at in Phase 3 anymore. The primary endpoint in Phase 3 is grip strength, and for them, it's been changed now to the four-week average. That's what's going to matter in Phase 3. Big differences between us and Mpacipibart, and I'll wrap it up here, on efficacy or potency, we are 30 times, 8 times more potent than Mpacipibart at shutting down the classical pathway at the IC90. So a reminder, if you like the data you see from their phase 3, we should be able to at least achieve that. If you're kind of have mixed feelings about their Phase III data and MMN, we can do better. We really shut down the classical pathway. I'm not sure what they're dosing, if they're really shutting down the classical pathway. Secondly, they block the lectin pathway. It's a C2 inhibitor. We don't. We leave the lectin alternate pathway intact. Why is that important? The lectin pathway is a pathway that gets triggered by the presence of encapsulated bacteria. That's the pathway that then allows the alternate pathway to rev up and together they form the MAC needed to destroy the bacteria. If you shut down the classical antlectin pathway, there's really no way for the complement system to respond to the presence of encapsulated bacteria and prevent the potential for things like meningitis. They're very likely going to have a box warning in a REMS program. Finally, where an auto-injector depicts in the same one auto-injector, two milliliter low volume, once every two weeks, self-administered, they're in IV every month. Those are the major differences between us and M.P.S. Superbar. And with that...

Yatin Suneja, Analyst — Guggenheim

Thank you, Marino. Thank you for setting the stage. Maybe we'll just pick on MMN first. I mean, it's a pretty bold statement. You're saying that you could have just gone straight into phase three if you knew how the phase three is going to be structured. So what is the, like, what do you need to see in this phase two study? A directional trend? I mean, it's 15 patients, so probably can't reach stats, so maybe help us understand.

Marino Garcia, CEO

Young, there's almost nothing that we'll see in our phase two that prevents us to go to phase three. It's a very small study. It's primarily safety, and I can tell you on a safety basis, on a blinded basis, it looks exactly like the MG and the CIDP trials look. There is nothing going on on a safety front that we go, oh man, I hope that's a placebo patient, for example. Nothing. There's almost nothing preventing us from going to phase three. We know we shut down the classical pathway. We know MMN is IgM-driven and classical pathway-driven. We know this is the highest unmet need of the three indications. It is underestimated. It is severely underdiagnosed because there's really no very effective biologics. IVIG is approved and it works for some patients, but I think most neurologists will tell you the efficacy wanes. The disease still progresses over time. Yeah. It is quite hopeless for a lot of MMM patients if we believe we have a therapy for them. So there's almost nothing that we'll see in phase two that prevents us from going to phase three.

Yatin Suneja, Analyst — Guggenheim

But you would want to see some directional trend on grip strength, right? I mean, just, I mean, I understand safety. Sure, sure. Yeah, I mean, we're going to look at multiple efficacy measures, and we're expecting to see some trend, of course. But the street, I could tell you, is nervous going into this. Maybe not because of you, maybe because of the competitor, but there is some nervousness going into it.

Marino Garcia, CEO

When are investors not nervous? Look, all I'll remind you is, before MG data, oh, are you guys dosing enough in MG? 300 milligrams every two weeks. Efficacy in a small 20-patient study. STAT-SIG week one. STAT-SIG every week to week 13. The highest minimal symptom expression percentage of patients in any complement study ever. In a 20-patient study with 300 milligrams every two weeks. Oh, are you going to have enough efficacy in CIDP? You're dosing one quarter of the amount. Relipid BART, they dose four times more than you do. Their phase 2 open label, 50% respond to rates. Our open label, Part A, 75% respond to rates. I mean, it is clear we have a very potent active C1S inhibitor and classical pathway inhibitor. If you believe classical pathway inhibition works in MNMN... We will work. So my point to you is if you're nervous about Argenix because it is not a very powerful classical pathway inhibitor, if you like the data, great. We'll be at least the same. But if you're not that impressed with the data, we have the opportunity to do better. Just like we did better than Relipobart. Potency matters in CIDP. I suspect it may matter in MMA. I don't know. But MMN looks more like CIDP than it does MG. So look at our efficacy difference in CIDP, and that response rate is staying high, despite having more than double the number of patients now that have finished Part A. I'm telling you, in MMN, I hope they are successful, and maybe modulating the classical pathway is enough. We shut it down. So, whatever they can do, we can do same or better.

Yatin Suneja, Analyst — Guggenheim

Got it. We then move to CIDP. You provided an update on the third quarter call where you're saying that you conservatively need less than 200 patients in part A. Maybe give a little bit more color there. Why? And then I think why conservative within the court?

Marino Garcia, CEO

Why say less than 200 patients? That's just us signaling very clearly that. There's almost no chance we even need to get anywhere close to 200 patients to finish part A to finish enrolling 128 patients in part B. I mean... We've constantly been moving that Part A number down. And we've tried to be conservative. At first, we had a 40% assumption, then a 50% assumption. This is now somewhere around 60-plus percent assumption. I'm telling you, it's conservative. So we just don't want to give a specific number because until we finish Part A, and we will reveal all the data from Part A when we're done recruiting, when we have that 128th patient go into Part B, we'll do that next year. But I'm telling you, We don't need 200 patients.

Yatin Suneja, Analyst — Guggenheim

How are the response rates holding? So you disclosed 75%, now you're saying you're more than double, but it's holding? And what is the reason, like, why you are driving that number 75% when you look at the liprobar, the number was much lower? Is it about the patient population, what you're doing from screening, like, what is happening?

Marino Garcia, CEO

All I can tell you is we're seven times more potent. So what does that mean, this graph in the middle, that we're seven times more potent? It says that to achieve 90% inhibition, according to this assay, you need to achieve PK levels that are seven times higher than us. So for this experiment, it says if we're somewhere around 100 micrograms per ml, we're shutting down the classical pathway, and that they would have to be somewhere around 668 micrograms per ml to shut down the classical pathway. So they would have to give seven times more drug than us. Assuming similar bioavailability, they would have to give seven to eight times more drug than us to achieve the same level inhibition. They're only giving four times more drug. They're doing eight shots a month. We're doing two shots a month in CIDP. So think about that. That means they're probably achieving half that PK level. What level of inhibition of the classical pathway is that? We don't know because they won't disclose. They haven't disclosed what their steady state is at 600 milligrams, two shots every week. We've told you what our steady state is with 300 milligrams once every two weeks. We're around 100 to 120 micrograms per ml on average in humans. We know with one shot every two weeks, we're above 90% inhibition. This is saying that they should be dosing. Seven or eight times more injections than us. In other words, 14 to 16 injections a month, not eight. That's why we're seeing better efficacy. I think in CIDP, it matters. Potency matters. It's about preventing C3A, C3B, and we think the higher level of inhibition you can achieve a classical pathway, the more efficacy you get in CIDP.

Yatin Suneja, Analyst — Guggenheim

I get it. I think the potency matters. What about the patient mix? What are you seeing in part A? Yeah.

Marino Garcia, CEO

So look, I can't speak to Sanofi what they did. I can only go by what I've heard secondhand and rumors. They were under a lot of pressure to speed up their trials because they were falling behind. They kept delaying their trials while we were advancing ours, and they were losing their first market advantage to us. So I know the marketing people in Sanofi were upset with that. Did they allow patients into their trial that they shouldn't have? Maybe. I'll tell you something that should reassure investors. Our screen failure rate in our CIDP trial at Part A is above 50%, close 60%. What does that mean? That means 6 out of 10 patients that investigators say, hey, this patient should be in our trial. When we review it, when our independent review board reviews it, we say, we're not sure. We're not sure they have CIDP. We're not sure if they have CIDP that it's active disease. So we're not going to let them come into the trial. That's created a little bit of frustration, but we are being super diligent. We are not allowing anybody to go into Part A unless we are sure they have CIDP and it's active disease. Did Sanofi do that? I don't know. So despite that, we're moving our timelines ahead. And that's because of the amazing team we have that's, you know, we're in over 200 sites and they're doing a great job of making sure that we're recruiting enough patients. And because of the elevated efficacy responder rates we're seeing in part A. So our part B is ahead of schedule. That's despite almost six out of ten patients that come into part, or trying to come into part A, we are screen failing. Did Sanofi do that? I'm not sure.

Yatin Suneja, Analyst — Guggenheim

Okay. With regard to the part A disclosure, what are you allowed to disclose? Can you disclose, given that the study is a pivotal study and it's still ongoing?

Marino Garcia, CEO

Remember, the FDA doesn't care about part A, because that's open label. What they care is part B. Part B is the randomized placebo withdrawal study. That's the part you really need to protect. Part A, we said 75% responder and we reveal it. We're not biasing the trial. This is open label. The investigators are seeing it. They're seeing their patients respond. It's all patients are seeing it themselves. So there's nothing we're disclosing that's, you know. That's not already out there. What we didn't disclose is what's the responder rates for naive, refractory, and standard of care stable. That we didn't want to reveal because that could bias investigators and patients. I see. Right? If you see higher response rates with naive patients, they may start only trying to get naive patients into the trial. We don't want to do that. Once we're done enrolling Part A, we're done. Then we can reveal to the world, how did naive patients do? How did refractory patients do? How did standard care patients do? How did IVIG patients do? Because at that point, there's no bias you can introduce. Everybody that you need is in Part B. It's placebo-controlled and blinded, and it's just waiting a year. To see what the results look like. And the reason we have to wait a year in Part B, I just want to be clear. It is a 12-month study. Because we have a 60-day half-life. And patients who respond in Part A to our drug, if they get randomized to placebo, you need to give them at least two to three half-lives for the drug to wash out. That's up to six months. And then they may start relapsing. Maybe they'll relapse sooner. But you want to give them at least six months for the drug to wash out. Got it. So that's why Part B is a full year. But at that point, when we're done recruiting and Part A is finished, we're no longer allowing patients into Part A. There's no reason for us not to share that data with investors. There's no bias we can introduce into the trial. The FDA is going to be laser focused on Part B.

Yatin Suneja, Analyst — Guggenheim

Got it. Then moving on to GMG, make some comments on the market. I mean, the market seems to be still growing. Substantial uptake you're taking with even, are you seeing with Uplizna. What is your view on the market? Where are you on the enrollment and the study front?

Marino Garcia, CEO

We're doing really well with phase three. No update there. We're still looking for data in the second half of 28. Sometime next year, obviously, I'll provide another update. We'll see as more sites are activated and recruiting, we'll see how we track to our timelines. Yeah, look, all I can say is less than 20% of... Patients who are ACHR positive with MG are on biologics. That's after a decade of complement inhibitors and FCRNs. Why is that? Why isn't it 40-50% like some other autoimmune markets? Well, it's because there's no simple rapid auto-injectors with no box warning, with good consistent rapid efficacy. There's nothing like it. Clacipibart is the ideal drug. Think about yourselves as very active, busy, traveling, you know, professionals. If you had an MG and, you know, you've got iTrulo with its 12, 10 to 12 steps and 90 second injections every single week, or you got IV infusions that you have to be wherever you get your infusion to get it on those dates, and you can't, you know, be traveling or do whatever you want on those specific times. Think about all of a sudden there's this auto-injector, like a Dupixen auto-injector, you keep it refrigerated, potentially you can keep it at room temperature up to four weeks. You just take it with you and you just travel. And then when it's time to take it, like a GLP-1, you're in your room, you wake up while you're sipping your coffee, wipe, five-second injection, click, done. You don't see the needle, barely feel it, honestly, the low level of injection site reactions, and literally, no, we're not seeing any complaints from the subcutaneous administration of claspibabart. That, if you had that available, why would you delay the use of biologics? This is the ideal drug to get to 40, 50% penetration. So, MG... All I will say is this. Oplizna, it's great to have another option. Congratulations, Amgen, and patience. But if you look at it, a CD19, it's not the best tolerated. You're going to have to wait months to see if it works on you. The only reason that is going to be a blockbuster in its first year is because it's once every six months in fusion. Just that convenience advantage over other IV administered drugs on the market is going to make it a blockbuster in its first year. Think about that. And if you were told that you have to wait months, and maybe wait six months of your life to find out it doesn't work on you, versus something like claspibibide, within seven days, you'll know. We separated from placebo in seven days in a small 20-patient study. Same thing with QMG, not just the MG-ADL, QMG. Think about that. Why would you want to what do some, take a drug that takes months to work? I mean, that speaks to how much need there is still in MG. It is not a saturated market. That market should be two to three times larger in terms of biologics.

Yatin Suneja, Analyst — Guggenheim

Got it. Very good. Maybe move to pipeline. I mean, I think for the size of your company, I mean, you have brought in new assets, really working on the pipeline. So talk about the 312, the BAF, April, and then the second program that you have. What are some of the updates from there?

Marino Garcia, CEO

2-1-2 is our next clinical stage product. It's the BGCA2 in Baphapril. It is still in phase one. We will have an update on our Healthy Volunteer Part 8 data early in 2027, the first quarter. We do have already our first SLE patients dosed in a SAD study with 212. So it's very exciting. It's all being done right now in China by our partner. And our goal is to start the MAD study in 2027. We'll then take over the MAD portion and start that outside of China and take over the program. Again, the idea there is we have a more potent PDC depleter than lidofilumab, which will have two phase three SLE readouts in December. We have what looks like POVY-like reductions in IG levels, but with a longer half-life, so potentially at least once a month, maybe less frequent. Subcutaneous self-administration is what we're aiming for. And the idea there, again, is to bring about superior efficacy to either mechanism alone. And then 312 is the Senshi class Saper Bard. It's exactly the same as class apribart on the active C1S inhibition side, but with PAF APRIL, POVI-like efficacy. And there, it's to go even further upstream. B-cell depletion plus classical pathway inhibition in diseases like MG, CIDP, and MMM. And again, the idea there is more patients responding, more robust response rates. We're very excited about that one. And then that could potentially go into other indications, of course, beyond MG, CIDP, and MMM. That's preclinical. That'll be phase one ready by the end of next year.

Yatin Suneja, Analyst — Guggenheim

End of next year. For 312, what indication or ADS you could go?

Marino Garcia, CEO

312, like I said, MG, CIDP, and MMM are no-brainers. Like, we will have already a lot of equity in those markets and a lot of good experience with active C1S inhibition, potentially even with BAF April's from VOR and from Vertex. And then for us to come out to those markets and say, hey, now we have two mechanisms in one antibody to potentially get you even better, deeper, more patients, responders in terms of efficacy. And then we'll go into other indications. We haven't said which other ones we might target, but certainly MG, CIP, and MMN are no-brainers.

Yatin Suneja, Analyst — Guggenheim

Got it. Maybe a final question on the capital or the cash position and how you are funded.

Marino Garcia, CEO

Yeah, we're very fortunate. We have $1.2 billion, and that takes us into 2030 and able to read out all the important catalysts and milestones between now and then for all three programs. And, yeah, I mean, the team is just doing an excellent job executing. So, we're in a really good position.

Yatin Suneja, Analyst — Guggenheim

Well, thank you, Marino. That's all I had for you.

Marino Garcia, CEO

Thank you.

Yatin Suneja, Analyst — Guggenheim

Appreciate it. Thank you.