Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos , a biotech analyst with Cantor. With us, we have Dianthus Therapeutics, a company I cover, and I'm pleased to introduce CEO Marino Garcia. Let's start off with a brief introduction of yourselves, followed by a snapshot of the company. Marino, when I initiated coverage in 2024, Dianthus had a market cap in the $600 million range, and now you're close to $6 billion. What happened?
That's a great way to start. Thank you. Let me just start by saying thank you, Pete, for hosting us and doing this seminar or this webinar this morning. Look, it's been just a tremendous last 12 months. I'll start just by giving a quick overview on claseprubart, our lead program. It's a very potent, active C1s inhibitor with a YTE half-life extension.
12 months ago, actually, around this week, we announced the top-line results from our phase II myasthenia gravis trial, and frankly, the data was much better than expected. We had statistically significant improvement within the first week on both the MG-ADL and the QMG, and that statistical significance was maintained through the end of the study to 13 weeks. That was a big first pivotal moment for us.
Earlier this year, we read out the results from our interim responder analysis for our CIDP phase III study. That also beat expectations, both our own expectations as well as I think investors'. From our perspective, claseprubart, we now see it as a de-risked, very potent, very effective neuromuscular therapy. What's next for claseprubart?
We have our third indication, MMN, and it's a small exploratory phase II study that we will read out in the month of December this year. We had initially planned for 12 patients per arm. We're testing two doses as well as placebo, of course. It was initially aiming for about 12 patients per arm. But we announced we over-enrolled. There was a really good enthusiasm out there for claseprubart and MMN. So we have about 15 patients per arm. It's primarily a safety study.
That really is what it was designed for. I can tell you on a blinded basis, the data looks exactly the same as MG and CIDP. Very clean. So no surprises. All the efficacy measures, including grip strength, which now looks like may be the primary endpoint in a phase III study.
If you look at argenx's MMN phase III study with empasiprubart, their C2 inhibitor, grip strength is now the primary endpoint. So grip strength and the other muscle strength measures are all secondary and really exploratory. What should investors expect? We're looking for trends.
We're just looking for the numbers to be moving in the right direction. There should not be any statistical significance versus placebo. It's a very small study, so very similar to the phase II that argenx had for empasiprubart and MMN.
The other big milestone coming up for claseprubart is we will provide further updates on our CIDP program. What I will be able to update investors on is when to expect the top-line results for the whole trial, for Part B, the blinded randomized withdrawal portion of the trial. When exactly will we be done with this phase III trial?
Also give a little bit of direction in terms of what N do we really think we need in Part A of this phase III study. Just a reminder that only people who respond to claseprubart above and beyond where they come in at baseline, for example, on standard care of IVIG, only patients who do better on claseprubart 300 milligrams, 2 milliliters every two weeks, only those then get randomized to Part B. Right now we are saying up to 256 patients are required in Part A.
But honestly, if we see the current trend continue, the current trend being the efficacy or responder rates very consistent with what we announced earlier this year. If we see this current trend continue into the future, we will not need anywhere close to 256 patients. We may be able to get the study done even faster.
We just recently announced that we started the phase III program for myasthenia gravis testing once every two weeks but also once every four weeks versus placebo. That is well on track, and we will have results for that phase III in the second half of 2028.
Claseprubart is what is really driving this growth in our market cap based on your question. We have a very exciting pipeline behind it. I do not think that is really being appreciated just yet, but I understand they are fairly early.
Yeah.
DNTH212, maybe we will get into that later, is still in its single-dose healthy volunteer phase I study being done in China. We recently announced DNTH312, which is where we are taking claseprubart and combining it with BAFF/APRIL or TACI, and that will be phase I ready by the end of next year. But the team's execution and the data that has been delivered with claseprubart, I think, is what has really resulted in this nice appreciation in our market cap.
It is great to watch.
Yeah. It's great to watch from my side, too.
All right, let's start off with CIDP. Back in March, like you just said, you announced the early goal decision for CAPTIVATE. Just describe the overall trial design and why do you believe it's the right design that increases the probability of success, and how does it differ from some of your competitors?
It's a great question. CAPTIVATE, our phase III trial, is a two-part trial, and it's really modeled on the ADHERE trial from argenx, which they conducted in CIDP and got them a very nice label for efgartigimod. It's a two-part trial. The first part is we confirm that patients have CIDP, multiple steps. The investigators have to confirm the patients have CIDP and it's active disease.
We have an independent review board, panel of three different KOLs. Each one has to independently of each other in a blinded way look at every patient and decide and say, "Yes, this patient has CIDP, and it's active." And of course, we also have to agree. Those patients then come into our trial. They could be naive to standard care. They can be on standard care, including IVIG, or they could be refractory.
And what we saw in our first 40 patients, which we revealed earlier this year, is about 10% are naive, about a quarter are refractory, and two-thirds are standard care stable. What do we do? We take those patients, we take them off standard of care if they're on standard care, including IVIG, and we switch them right away to claseprubart, open label, 300 milligrams every two weeks.
And only patients that do better, they have to improve, not stay stable, but improve further in a very clear, robust way, in a consistent way over two different visits after week 5. Only those then get randomized to the blinded randomized withdrawal portion of the trial, part B.
And there it's a 12-month period where patients who are randomized to either continue on the 300 mg, 2 ml every 2 weeks, sub-Q, or they're randomized into placebo. It's a full year, and the reason for that is unlike with efgartigimod, we're not going to have patients start relapsing very quickly because we have a 60-day half-life. We're giving them at least 2, 3 half-lives before we expect anybody to start to relapse, and that's a good 6 months.
Yeah.
That's going to be a really nice advantage for us when we market the product because I think it'll be very comforting for patients that if, assuming it's approved, of course, and it's dosed once every 2 weeks, if a patient somehow forgets to self-administer one shot, they don't need to panic. This has a nice long half-life.
They can just take it a few days later or even just go to the next dose. I think that's going to be a really nice comforting message. The big difference between our trial and efgartigimod's trial in CIDP is really upfront.
First, they didn't allow any refractory patients into their trial. The reason you wouldn't allow refractory patients if you're studying an FcRn in CIDP is that if IVIG didn't work, it's very unlikely an FcRn is going to work. FcRns are not as effective as IVIG in CIDP.
They're just much more patient-friendly, much easier to take, much better tolerability. We do allow refractory patients. Secondly, what argenx did is they took patients off IVIG standard care, and they had to relapse by at least 1.9 I-RODS scores. They had to relapse before then they were allowed to take efgartigimod.
Patients that improved after that relapse, only those then were randomized into part B, but only two-thirds of patients were able to improve after being taken off IVIG. Think about that. When you see a 67% or so improvement in part A for efgartigimod, you have to remember that's after patients relapse.
Only two-thirds were able to get back to their baseline to feeling like the way when they came in. We don't do that, and there's no CIDP trials in the future are going to be able to do that again.
You won't be able to get any enrollment. No investigators are going to participate in that kind of trial anymore. It's a brutal thing to do to patients. We switch, and you have to do better than how you were doing on IVIG.
Otherwise, you don't go into our part B. That switching data is also going to be really powerful if the drug is approved in CIDP. Think about it. It's telling physicians, "Here's what you should expect if you just switch your patient off IVIG within a week to our drug.
Yeah.
We will have that data from the open label portion, and then the comfort of knowing that efficacy will be sustained because we will have a one-year blinded portion after that. It is a really great study. Kudos to argenx for designing it. We made some slight improvements, we feel, to it, and so far, the results have just really exceeded all our internal and I think as well as external expectations.
Well, you did mention. Well, you did disclose the results back in March, earlier than anticipated. I think it was supposed to be 2Q.
It also speaks to the company's ability to execute. You then provided additional details in June, just a brief synopsis of what you showed.
Let me just, again, the team, that is the one thing I am proudest of for the last few years. It is just the team that we have been able to put together and their execution. I talk a lot about claseprubart.
It is a great therapy, of course, and we are very proud of that, but the execution makes a big difference here. So yeah, no, we announced an early go decision because in the first 40 patients in our open label portion, we were expecting to see about 20 patients responding and therefore being randomized to part B.
Those 20 patient responders, we found them much earlier. It happened much earlier in the trial, and the trends we were seeing for the remaining number of patients before we even got to 40, it was clear we were going to exceed expectations. We said, "Well, why wait? Let's just announce that we are a go." Later in June, we presented the actual data for the first 40 patients.
Our target had always been that we would see about 40%-50% responders. That was based on the phase II riliprubart data, which was also open label, and that's what they saw. Depending on which stage of the phase II trial, the response rates were somewhere around 40%-50% patients getting better above and beyond standard care. We're at 75%.
Yeah.
That is not something we had planned for. This trial has just, on every level, exceeded expectations, and certainly the timelines have been cut. If riliprubart were to get to market, we have significantly cut their first-to-market advantage, and we are getting very close.
The question now is because of their failed MOBILIZE trial, which they announced in June, which is one of their two placebo-controlled trials in CIDP, the only indication that I believe they're pursuing.
With that study being cut short and ended, not sure how they're going to get approval with only one placebo-controlled trial. VITALIZE, the second trial they have going on, is a go, and they're continuing to enroll there. We'll see. It's a race to be the first classical pathway inhibitor into the CIDP market.
All right. You did shorten the study a bit, like when these data were announced, you did modifications to the trial design, and then again, there's a possibility of another modification?
Yeah. First, we got rid of the 600 arm in part B. We know we don't need that. It's just not possible to exceed the efficacy we're seeing with 300 milligrams every 2 weeks. We shortened part B. That obviously then means we can make part A smaller.
We also raised the bar to at least 50% responder rate in part A, so we came up to 256 from, I can't remember, it was over 400 patients we thought we might need in part A at the start of the trial.
Like I said, that 75% responder rate earlier this year really exceeded expectations, and I can say the trend right now looks very consistent, and we have many more patients in part A. If that continues, you just do the math.
Yeah.
You don't need 250 patients in part A, because the real critical piece of this trial is we need to get 128 patients into part B. It's 64 per arm. Again, you can do the math. If the efficacy rates remain anywhere close to what we've seen and what we're still seeing now, we're not going to need anywhere close to that 256 number.
All right, what I'm also garnering is that you may actually complete this study before gMG. What would sort of be the filing strategy? Would you actually try to file based on a single study?
What I will say, as of today, we still expect MG to come in first, and then CIDP after. The plan is still that the initial BLA is MG, and then maybe very soon after, we submit the CIDP sBLA with the single Phase III study. If that changes in the future, then we can have a conversation about how we're going to tackle that. That is a scenario we're thinking through and planning for as well.
Okay. CIDP, IVIG remains the efficacy bar. When the FcRns and VYVGART, just establishes a better-tolerated alternative. How do you see claseprubart fitting into the emerging treatment paradigm, and how big is the opportunity in the U.S.?
Yeah. CIDP honestly is now becoming very likely at least as big as MG for us in terms of commercial opportunity, if not bigger. If you can imagine a scenario in the future where you have three options. Where you have an FcRn, you have IVIG, the gold standard for many, many years. We know it works. Then let's assume claseprubart. IVIG works.
If you talk to patients who are on it, where it works for them, they thank God for it. But the next thing they'll tell you is how much they hate taking it and how the efficacy wanes a little bit at the end.
There are side effects. Their full day of sitting to get the infusion. The fact that the next day after the therapy, they feel too sick, and it takes a couple of days before they can start feeling normal.
It's a lot for the patients to take. The number one group of patients who are coming into our trial are patients who are on standard care and stable. Think about that. If you have CIDP and you're stable on your therapy, what's your motivation to go into a trial and try something new? It's just you really want to get off IVIG.
Yeah.
If there's something out there that could potentially be at least as good. Now, think about what the physicians and the patients are going to face. So you've got IVIG. Okay, we understand that. FcRn, definitely better tolerate. Definitely much more patient-friendly. Weekly injections, but it's just not as efficacious. IVIG wipes out your IG.
Yeah.
We know FcRns don't wipe out all IG, so it just makes sense. Hopefully, some patients might try that first, and if it works for them, boom, you're perfect. You're done. You don't need to go to anything else. But if you're on IVIG and stable, you really risk a relapse, and that's a bit scary for patients. If you're refractory, it's very unlikely an FcRn is going to work.
Then you'll have claseprubart. Auto-injector, 5 to 10 seconds. Literally, if you want to know what it is, just go to the DUPIXENT website, look at the patient video for their auto-injector. We're using the exact same auto-injector, same dose every two weeks. The data we will have is that for the vast majority of patients, if they're switched, they will get better, not even stay stable. Some will stay stable, and that's fine.
That might be a win if you're already doing well on IVIG, but you just want to get to something easier. Our data will show that a big percentage of those patients are actually going to do even better when they switch to our drug, and they get to use an auto-injector and self-administer and travel the world if they need to. You'll be able to keep this in the fridge, and it'll be stable at room temperature anywhere from 2-4 weeks.
Yeah.
I mean, you literally just give it to yourself wherever you are around the world. It's super easy with a really great tolerability profile. No box warning, no REMS program, unlike IVIG. I'd ask you, what would you want if you were a CIDP patient? Which therapy would you go for first?
I think we're going to position as a first-line therapy, and certainly the first switch for patients that maybe had to try IVIG or were put on IVIG first, or certainly are on FcRn and maybe it didn't quite work well enough for them. The pricing is interesting. I mean, we are aiming for once a month in MG.
Yes.
That market, we'll price it to be competitive with FcRns, but our dosing in MMN and CIDP will be once every 2 weeks. Those are smaller markets. So you asked me about the size opportunity. Look, in the U.S., we think the AChR positive MG market is about 100,000 patients.
For CIDP, we think it's about 40,000 patients. For MMN, we think right now it's about 10,000, but MMN, like CIDP, we believe is severely underdiagnosed. I mean, you have to remember, MG, we thought maybe it was closer to the size of CIDP market just a decade ago, and look how it's evolved as new therapies are approved and physicians have more motivation to diagnose.
Yeah. My numbers put it a little bit higher than 100.
In MG? There you go. I think CIDP is underestimated, but it's about 40,000 right now, from what we can see out there in the data. I think that'll grow. That's U.S. alone as well. But the unmet need is huge. It's definitely a less crowded space. I'm very excited about the opportunity in CIDP for sure.
MMN, how big is that opportunity?
Right now we're saying it's about 10,000, but if you talk to a neurologist, the first thing they'll tell you is that it's severely underdiagnosed. We believe that there's many more patients with MMN out there who are going undiagnosed. But right now we're saying it's about 10,000 in the U.S. We project that'll grow significantly over the next few years.
Okay. I can go on and on with clinical studies, but let's just touch on your newer pipeline assets. Just a few weeks ago you disclosed DNTH312, which combines two mechanisms of complement inhibition and B-cell modulation. Just tell us more about that asset and what led you to combine those two MOAs into a single molecule.
I think it's one of those where once you see it, you go, "Wow, of course. Why didn't we do this earlier?" It is something that we've been working on for a while, and I'm very proud of our small but mighty research team that was able to come up with this internally. The idea here is we have multiple BAFF/APRILs now that are doing MG studies.
Including Vor and Vertex, and they're very likely to have positive data. We'll see how positive, but they'll likely have positive data. We know active C1s inhibition works in MG, CIDP, and we also feel very confident, of course, it'll work in MMN. We know MMN is a classical pathway-driven disease.
The idea here is if you could put what could be a best-in-class BAFF/APRIL, so something that's at least as good as povetacicept, potentially better, and combine it with our highly potent active C1s inhibitor, claseprubart, you are able to go.
We're already upstream in the complement system. You go even further upstream with the B-cell modulation. I think the idea here is not that we would have one plus one equals two in terms of efficacy improvement, but it could be one plus one equals one and a half.
I mean, we could have a much more efficacious therapy in MG, for example. Many more patients could respond. We could go into even those who are not AChR positive patients and other types of myasthenia gravis patients with this therapy. Same with CIDP and MMN. I mean, it is really about a play for a subcutaneous self-administered therapy where we could bring about even better efficacy.
That is a nice way to continue to evolve our future leadership role in the neuromuscular space. Think about this, Pete. What I love especially about it as a CEO is, I have this clinical development team, clinical operations team, regulatory team, which are just an amazing group of people. Really, really amazing what they've been able to do.
Just as they'll be done with these three indications and handing it off to the commercial organization, all of a sudden we have DNTH312. All the lessons learned, all the expertise built up, all the relationships and the connections made around the world with all the best clinical sites and KOLs. We can apply all that to DNTH312.
Leverage
move very quickly and efficiently. I don't have to grow the organization like I would if it was a completely different area, different mechanism. We're taking DNTH312 definitely into the three indications, neuromuscular indications that claseprubart is in, and then we can expand even further to other indications.
I'm so excited about that one. I know it's early, but the good news now is any data from our BAFF/APRIL competitors in the MG space is now going to become a positive catalyst for Dianthus.
For certain complement-mediated diseases, you sort of need a certain level or a minimum level of complement inhibition to achieve substantial efficacy. In these autoantibody-driven complement diseases like gMG, I think you can lower the minimum level of complement inhibition and still see efficacy. How are you thinking about this in terms of also including B-cell modulation? Will you actually lower the amount of complement inhibition needed?
It's a great question. In myasthenia gravis, we always suspected this, honestly, as a company, but the evidence is now mounting that even just being somewhere around 70% or levels of inhibition, like zilucoplan, will give you maximum efficacy, but that's for C5 inhibitors, so we'll see what that means for an active C1s inhibitor.
Look, I think what you just mentioned is what gives us confidence that our once-a-month dose in MG will probably very likely be very similar in terms of efficacy as our every two-week dose. But we're not taking the risk of not including an every two-week dose as well. It's a three-arm Phase III study, of course. We'll have to see.
If that data tells us that once a month is similar to once every two weeks, then I think a once-a-month therapy in MG, even when we combine it with tafapiral, is probably the right way to go. You never want to sacrifice on efficacy for convenience. There's no need to do that.
Yeah.
Efficacy is everything. These patients do not necessarily just want convenience, they want efficacy. That will always be what primarily, and of course, safety and tolerability, and that is what will drive our decision-making around DNTH312 dosing. It is really early. We are still about 18 months from a phase I study or less now that we are in September. Let us see what data we create with DNTH312 over the next couple of years.
All right. You obviously got a very great molecule, claseprubart, any potential, I know that you can add this onto a blood-brain barrier-crossing technology. The reason Sanofi is doing it, or Sanofi, with riliprubart, they did put it on. There is some preclinical data out there, but there are just so many other places that you can go with this molecule and do that.
I agree. Is there a question?
Yes.
I'll just say I agree. There's interesting. DNTH312 is an example of that. There's interesting things you can do with claseprubart.
All right.
It's such a great asset. I've been in the industry a long time, and I feel very fortunate that I have the team that I have, plus that I have the support from investors I have, of course, but also this amazing antibody, claseprubart. It's just exceeded all expectations.
A couple of minutes left, 2:12. Anything you'd like to touch on and sort of.
Yeah. It's our BDCA2 tafapiral inhibitor we brought in from China, from Nanjing Leads Biolabs, a fantastic group of people out in Shanghai. Yeah, we're in a phase I study. We'll have an update on how the single-dose healthy volunteer study is doing later this year and what our plans are for 2027. Assuming DNTH212 goes forward and there's no safety limitations or anything like that.
We do shut down the innate and adaptive immune system. So very fair to want to see the phase I data before we move ahead. But we are very confident that we are going to be moving this forward, and it could be a bigger value driver for the company in the next few years than even claseprubart is. The DNTH212 could go into much bigger indications, many more different, more indications than claseprubart even. So I'm really excited and optimistic about DNTH212 as well.
Right. So if it does trigger movement forward for Dianthus themselves, what do you expect to need to do? Will you do another PK/PD study in the Western population?
For DNTH212?
Yes.
Yeah, this is the single-dose portion of phase I. We have to do the MAD, so we'll provide an update on when we're going to start the MAD study in 2027, and then what our plans are to start dosing patients with DNTH212. That'll all be part of the update later this year.
Okay. Last question, sitting here 12 months from now, what would you like to say were key value-creating accomplishments by you and your team at Dianthus?
Good clean data with MMN. Hopefully, argenx also has positive data with empasiprubart and MMN in their phase III. We will have started our phase III study in MMN as well. Our plan is just to move as quickly as possible. There is almost no scenario I can imagine where we do not start a phase III with MMN. We will have further updates on MG and our CIDP program.
DNTH212 will be well into a MAD and potentially even start testing or having tested in patients. Again, I will provide an update on that later. Showing progress with DNTH312. Do we have any other news on our pipeline? Is there anything else coming up behind that that could be really interesting and exciting? Our goal here is to build a really. Look, you look at the success that argenx has had.
Their stock price and the kind of value they have created for patients as well as for shareholders. I think, if that maybe worked on their pipeline a little earlier, they could have more products launching and maybe a more exciting pipeline.
That is something I am very focused on. I do not want to be in a situation where I launch a blockbuster and then I have many years before I can launch another blockbuster. So our goal is to just continue to create excitement around the pipeline and have regular launches to feed into a commercial organization in the future. We are so well on track with that. I am very happy about that.
Great. Ran out of time. Marino, would like to thank you very much for partaking in our healthcare conference. Great to hear all the updates and looking forward to watching the company progress.
Yeah. Thank you, Pete. I really appreciate it.