Dianthus Therapeutics, Inc. (DNTH) Earnings Call Transcript & Summary

Good morning, and welcome to the 43rd Annual JPMorgan Healthcare Conference. My name is Dave Praharaj, and I'm part of the healthcare investment banking team. Today, I have the pleasure of introducing our speaker, Marino Garcia, CEO of Dianthus Therapeutics. In terms of logistics, please reserve any questions for after the presentation. For those in the audience, a mic will be passed around. And for those viewing on the web, please submit your questions online, and I'll be able to view them through the iPad on the stage. With that, take it away, Marino.

All right. Thank you, Dave, and thank you to JPMorgan for this opportunity to present today. I'm going to be making some forward-looking statements, so I would urge everybody to go to our website and you can see there our SEC statements and filings for more information. So we, the team, at Dianthus are building an exciting leading autoimmune company focused on rapidly advancing DNTH 103, our complement inhibitor that selectively inhibits the activated form of C1s and only inhibits the classical pathway. That's important because we're aiming to deliver robust efficacy, continuous symptom control and classical pathway-driven diseases while, at the same time, reducing the burn of treatment for patients in two important way. One is through a differentiated safety profile with the potential of a reduced risk from infections, from encapsulate bacteria as well as an improvement in the dosing and administration and convenience for patients. The intention with 103 by going after active C1s is that we -- because of its low volume, we could potentially put it into auto injector, a 2 millimeter, 300-milligram shot that can then be delivered through a convenient auto-injector as infrequently as every 2 weeks. So a Dupixent-like dosing and administration profile. We believe we have a best-in-class complement inhibitor, and that's supported by Phase I data that confirmed that we have a robust long 60-day half-life that supports the infrequent dosing as well as that differentiated safety profile referred to it. And we also now have head-to-head data that shows very clear superior potency versus our direct competitor, riliprubart, another active C1s inhibitor in Sanofi's pipeline. The pipeline of product potential with 103, as it is with any complement inhibitors, is now validated through clinical proof of concept across 3 neuromuscular conditions, myasthenia gravis, CIDP and MMN. It's a very exciting time for Dianthus, 2025, we have very near-term catalysts, starting with we are recruiting and on track to delivering our Phase II myasthenia gravis data later this year, in the second half of this year. We're right on the cusp of delivering that data between Q3 and Q4. So as soon as I have clear certainty on which quarter the data will fall in, I'll update guidance. And then within 12 months after that, we'll have our first Phase II data in MMN as well. And then as we recently disclosed, we have one single Phase III pivotal program going on with CIDP. And in the second half of '26, we will be able to put out our interim responder analysis with our first 40 patients recruited into that program. And really good news and very fortunate, we have a very strong balance sheet and enough cash to take us into the second half of '27 and be able to read out on those 3 important catalyst, near-term catalysts for Dianthus and 103. Mentioned the pipeline and our product potential. We really believe 103 has the potential to be a first sign best-in-class biologic across multiple indications. So we've decided to focus first on building a neuromuscular franchise with these 3 first indications. Generalized myasthenia gravis, chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. Combined, these markets represent over at least 100,000 patients in the U.S. And all 3 have important dynamics that -- where we could bring real value to patients with 103. With MG, we know it's a multibillion-dollar market, supporting already multiple blockbusters that's hungry for new mechanisms of action and the unique benefits that 103 could bring. And with one MMN and CIDP, what's exciting is in the recent past, we now have proof of concept for classical pathway inhibition, delivering the robust efficacy done through riliprubart, Sanofi's active C1s inhibitor in CIDP as well as with Empasiprubart, the C2 the inhibitor in Argenx pipeline. So the opportunity for 103 to be that first-line biologic choice across all these 3 indications, starting with MG that there's a unique opportunity for a classical pathway inhibitor that can deliver continuous robust symptom control while at the same time, reducing that burn for patients by reducing the risk of infections from encapsulated bacteria as well as delivering a more convenient dosing administration therapy for these patients. In chronic inflammatory demyelinating polyneuropathy, we have riliprubart, which has shown great efficacy with patients who are in IVIG, the current standard of care who are refractory or stable or even naive to IVIG switch back to C1s inhibition. Well, we have had to had data that shows that we are significantly more potent and I'll get into that in a few slides. And finally, within MMN, with Empasiprubart, we know that they validated classical pathway inhibition as delivering excellent efficacy. And there's now there an opportunity with a very limited competition for a classical pathway inhibitor only to deliver a more convenient, safer option for those patients. Focusing now first on the opportunity within myasthenia gravis. This is a blockbuster market, supporting 2 first line biologic classes, which will remain the mainstays of therapy in the first-line biologic classes or therapies for the near future. First, we have complement inhibitors, the C5, obviously, from Alexion and AstraZeneca. Ultomiris driving their growth are over $6 billion, and that growth is coming mainly from the U.S. market with biologic naive MG patients. And then, of course, Efgartigimod with the FcRn class, a multi billion dollar market opportunity. And again, just really highlighting the need for new mechanism of action in this very large rare disease. The key aspects to consider within the MG market, we know MG as a chronic classical pathway driven disease. And we know C5's work because they shut down the formation of the MAC with patients who are AChR positive. The issue with the C5s, of course, is that there is the increased risk of infections from encapsulated bacteria because they also inhibit the formation of MAC if it was a complement system was triggered by the classical -- sorry, by the lectin and alternative pathway. And they have to be delivered, obviously, through an IV infusion. With Efgartigimod, the cyclic dosing presents a bit of a challenge for patients who are experiencing a chronic disease like MG, the fact that you have to go through a cycle of treatment but then come off treatment for a period of time. You have MG-ADL and QMG scores that are rebounding and coming back to baseline before they get their next treatment. Again, that has to be infused, either through an IV or subcu infused by health care professionals. So the key advantage here or the key opportunity for 103 is to deliver that robust continuous symptom control by being a potent classical pathway inhibitor, but do it by reducing that burn of not touching the lectin and alternative pathway and reducing the risk of infections from encapsulate bacteria like meningitis and at the same time, delivering it through a self-administered, very convenient, infrequent subcu auto injector. So I mentioned the -- reducing the patient burden, and it's in 2 very important ways. One, as I mentioned, is in terms of dosing and administration. When you look at everything that's approved today, whether it's the C5, with IV or even the self-administered cell brisk, which is a daily prefilled syringe injection that patients can self-administer, but it is a daily injection so not terribly convenient. There is nothing that can deliver that patient convenience and that reduced dosing administration burden like 103 can with its 300-milligram 2-milliliter subcutaneous, self-administered auto-injector every 2 weeks. But it's not just a dosing and patient convenience aspect. It's also the fact that we can reduce the safety burden. We know that classical pathway inhibition will work in myasthenia gravis. That's been validated by the C5 inhibitors. But as you can see here on this slide, the C5 fibers are terminal inhibitors. That means they're always going to have a safety warning, a box warning around the risk of infections from encapsulate bacteria because they don't just prevent the formation of MAC if the complement system was triggered through the classical pathway as it is with AChR-positive patients with MG. It also shuts down the formation of MAC if this complement system was triggered by the lectin and/or alternative pathway. And that means that you're preventing the ability for the complement system to fight against these deadly infection risks like meningitis. And in this theory that we will be able to lower the burden or the risk of infections and therefore, not have that box warning in the REMS program that's such a burden for patients as well as physicians and pharmacies is not pure theory. There is a precedent. As you can see, on this slide in Enjaymo, sutimlimab. It's a classical pathway inhibitor that's approved and on the U.S. market, is approved for cold agglutinins disease. It is the only classical pathway inhibitor that's been approved. It's also the only complement inhibitor that doesn't have a box warning for any safety issue and no REMS program. So that's a precedent that's been set with the FDA and then certainly a precedent we believe we will benefit from with the DNTH103, and patients will be benefiting from as well. Now moving to CIDP. It's a very attractive and growing market, much like MG was a few years ago. And what's really exciting is in the last year or so, we've seen validation for an active C1s inhibitor in delivering really robust efficacy for CIDP patients. This is the first time that an active C1s inhibitor has been shown to work in neuromuscular conditions. And it's the first time that a complement inhibitor has been shown to work in CIDP period. So riliprubart, an active C1s inhibitor Sanofi's pipeline, looked at 3 different patient groups. Those who were on standard of care IVIG but refractory, those who are on standard of care IVIG and stable, and those who were naive to IVIG. And in all 3 different types of patient groups, they switch them to their active C1s inhibitor. And they saw really impressive efficacy. On the right, you can see what happened with patients were naive to treatment. No surprise, very robust strong efficacy signal there. But what's really impressive is when you look at patients who are on IVIG and treated and stable, group A, or those who are refractory to IVIG. And I want to point out that FcRns would not work on these patients. If you're refractory to IVIG, it's very unlikely an FcRn will work since it's a very sort mechanism of action. In both those cases, when switched to active C1s inhibition, approximately half those patients improved further. That's a very powerful efficacy signal and really validates classical pathway inhibition as potentially being very unique benefit for patients or a significant number of patients who are suffering from CIDP. So of course, the question is then how do we compare to riliprubart? We'll point out that the dosing for riliprubart is 600 milligrams, 4 milliliters every week. If you were to try and put this into auto injectors, which can take up to 2 milliliters, we're talking about 2 auto injectors every week, so about 8 auto-injectors every month. We are targeting 1 auto-injector every 2 weeks, so 2 auto-injectors every month. So it would be 8 versus 2, 300-milligram 2-milliliter shot every 2 weeks and 1 auto-injector. And the question then becomes, well, how can we be confident we'll get similar, if not super efficacy to riliprubart in CIDP with a lower dose, less frequent dose. We conducted 6 different head-to-head in vitro PD potency experiments to demonstrate that we have a significantly more potent antibody active C1s inhibitor compared to riliprubart. We did this with using 2 different affinity assays, looking at [ Connect ] and SPR. We did one enzymatic assay looking at the prevention of cleavage of C4 and then 3 different functional assays. And you see across the board, the DNTH103 outperforms riliprubart when it comes to different ways of looking at its potency and comparing them head-to-head, same labs, same reagents. We even had third parties conduct some of these experiments as well to make sure that they validate the data that we were seeing. The CH50 hemolytic assay, the one here highlighted in the middle is the one that we really focus on. That's the one that tells us what we think we need to achieve in terms of dosing or PK levels to achieve at least 90% inhibition of the classical pathway. And there, you can see we're about 7x more potent. In other words, we need to achieve 7x lower PK levels or CMACs if you like, than a riliprubart in order to really shut down the classical pathway by a robust 90% or achieve the IC90. Focusing on MMN for a moment. This is a really nice opportunity as well. It's a smaller market, but it's one where there's very limited competition and FcRns won't work. Really, there's only one other competitor right now and that's Empasiprubart. It's a C2 inhibitor that has to be delivered through IV every week or every 2 weeks. And being a C2 inhibitor blocks a classical pathway as well as the lectin pathway. But their data is really impressive, and it really supports the fact that patients with MMN may have a very strong response to a classical pathway inhibitor. As we know, this is a classical pathway driven disease. So again, the question is, how will 103 differentiate itself versus Empasiprubart. With our 3 key considerations. First off, we know MMN is an IgM driven and classical pathway driven disease. We have very robust potency data that shows that 300-milligram 2 milliliters -- excuse me, every 2 weeks delivered subcutaneously will get us significantly above the IC90. In other words, we shut down the classical pathway by over 90% when we're dosing our target dose. We don't have that potency data for Empasiprubart. So we don't know how powerful it is at shutting down the classical the pathway. What we do know is that the lectin pathway is an important pathway to help fight against the infections from encapsulate bacteria. Empasiprubart blocks the lectin pathway. We don't. We are purely selective for the classical pathway. So we are going to be more effective in preserving the ability of the complement system to fight against encapsulate bacteria and the risks of in conditions like -- sorry, meningitis. And then finally, the dosing and administration convenience. It is an IV delivered every week or every 2 weeks. Again, we're aiming for a subcu auto-injector that patients can self-administer every 2 weeks. So as I mentioned, it's an exciting time for us. We will be delivering our first Phase II data in myasthenia gravis later this year. As I mentioned, the data is on the cusp of between Q3 and Q4. As soon as I have more certainty, I'll update guidance. And with multifocal motor neuropathy, we're on track with recruitment to deliver data in the second half of 2026, about a year after the MG data. And with chronic inflammatory or our CIDP program, I should say, we are a Phase III program. We're aiming to deliver interim responder analysis for that Phase III pivotal single program in the second half of 2026 again as well. So let me now talk a little bit about the clinical development program. We conducted 8 different cohorts and we have 60 patients -- sorry, healthy volunteers data that really confirmed that we potentially have a best-in-class complement inhibitor. So what we learned from our Phase I is on the left, as you can see, the IV SAD cohorts. Very nice linear PK, and it confirms that we have a nice long 60-day half-life. The middle graph shows that, of course, with a 60-day half life, if you dose every 2 weeks, you get nice accumulation. And then finally, on the right, what we did is we graphed the PDPK for 103 in every single healthy volunteer, every single cohort, every single data point. And what that holds us is in vivo our IC90, in other words, the levels we need to achieve to shut down the classical pathway by a very robust 90% of lease, it's about 87 micrograms per ml. That is the target with our dosing. So then we take all that data and we model it. And as you can see here on the graph on the right, the IC90 being at 87 micrograms per ml, our steady-state dosing 103 every 2 weeks hover somewhere between 115 and 125 micrograms per ml. So about an average of 120. That's a good 40% above the target levels. This is what gives us the confidence that if you are suffering from a disease like MG, CIDP and MMN, that is classical pathway driven that 103 at dose at 300 milligrams every 2 weeks will deliver on efficacy. We also saw a very, very favorable safety and tolerability profile from our Phase I. No serious adverse events, no infections from encapsulate bacteria. So again, giving us that confidence that we could potentially have a differentiated safety profile, especially compared to complement inhibitors that are not selective only for the classical pathway. So our MG trials I mentioned, that's going to read out in the second half of this year, somewhere on the cusp between Q3 and Q4. We're on track. We're testing 2 different doses, 300 milligrams, which I just showed you get to us nicely above IC90, and then 600 milligrams every 2 weeks to get us way up there above IC95. And it's just to conduct the experiment to see what happens if you shut down the classical pathway even more. Do you get any additional efficacy out of the antibody in a condition like myasthenia gravis. If the study is successful, by the way, the Phase III is identical. It's just larger numbers as we move the efficacy endpoints to be the primary endpoints. With CIDP, this is new information or very recent information we disclosed. We're very encouraged to see Argenx ADHERE trial, which conducted this single pivotal trial 2-part trial and led to an indication in June for all adults with CIDP. And we decided we were going to try to replicate it with a couple of important differences. So this is a single trial. We have the IND cleared, and we're starting this program, and we'll have interim responder analysis from the first 40 patients that are enrolled into Part A in the second half of 2026. Part A is we're taking patients who are on IVIG, potentially switching them to 103. And in Part A, it's open label, 300 milligrams every 2 weeks. If a patient with CIDP responds at any point starting week 5 in Part A, then they get randomized into the placebo controlled random Part B, where we are testing, again, 2 doses, 300 and 600 versus placebo, but only patients that respond to 103. Those who don't respond will drop out of the trial. So this is essentially kind of what Efgartigimod did in CIDP that led to this very attractive label that they have an approval on CIDP, where they're already seeing significant uptake and a lot of success. And we are essentially replicating this with, I would say, one important difference, and that is that we are allowing patients who are refractory to IVIG to come into this trial. Obviously, within FcRn, you wouldn't allow that. They didn't allow that because you don't expect FcRns to work if IVIG doesn't work. But as we saw with the riliprubart data, there's a very strong chance that a significant number of patients will benefit from a classical pathway inhibitor, a potent classical pathway inhibitor like 103 even if refractory to -- and difficult to treat and refractory to IVIG. And with MMN, we started that trial last year, a Phase II trial, and that is on track in terms of recruitment, and we're still planning for top line results. And again, we're testing 2 different doses like we are in MG, like in CIDP. We're expecting the top line results in the second half of 2026. So in summary, again, we're really excited about the potential for this product to be a best-in-class first line biologic across multiple indications, starting with MG, CIDP and MMN. And that's based on the very robust efficacy that we -- or potency, I should say, that we've seen in vitro and especially comparing ourselves head-to-head versus riliprubart, the half-life and the PK profile, supporting infrequent dosing and being able to be put into an auto-injector, much like a Dupixent. The ability to reduce the burden for patients in terms of the risk of infections from encapsulate bacteria and avoiding the box warning and the REMS program. And finally, the fact that we have a very strong IP takes us out to at least 2043 without any extensions. But in summary, as I just mentioned, just to wrap up, we're very -- the team has done a phenomenal job standing up these 3 programs last year. The level of execution from the Dianthus team makes me really, really proud. So I want to thank them for the effort they've put in especially as the CIDP program became a much more ambitious single Phase III pivotal program. So I look forward to delivering the -- we look forward to delivering the MG data into Phase II data later this year in a matter of months and continuing to execute against the MMN and CIDP program to deliver data in 2026. As I mentioned, we have a very strong cash balance that was about $343 million as of the end of the third quarter, which will take us beyond these 3 major data catalysts in the next 1.5 years, 2 years. Thank you very much. So I'll take questions if there are any.

I guess I'll ask one, just a brief one. I know you mentioned that you're targeting second half '25 for your MG top line data. Can you be any more specific than that?

Yes. So recruitment is going really well. And right now, when I look at it, our best estimates show that it could be end of Q3, beginning of Q4. And until I know for certain which quarter it's going to fall in, I'd rather just keep the guidance at second half. But in a matter of a very short period of time, I'll be able to get that confidence and then I'll update guidance and let people know exactly which quarter. But everything is going really well. It's going according to plan. It's just -- it's like right there on the cusp between those 2 quarters right in the middle of the second half.

Any questions from the audience?

All right. Well, thank you very much for inviting.

Thank you.