...Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos, a biotech analyst at Cantor. You know, with us today, we have Dianthus Therapeutics. It's a company that I launched coverage on earlier this year, and I'm pleased to introduce the CEO, Marino Garcia.
Thank you, Pete. Thanks for having us.
Yeah. So let's start off, you know, with a description of the company, your key therapeutic strategy, you know, which is focused on complement cascade, to address disease. You know, with many complement pathway inhibitors either approved or in development, you know, why do you see the need for the additional complement pathway?
Sure, so let me take a step back. Dianthus was founded in two thousand and nineteen with the idea of developing what we're calling next-generation complement therapeutics. That's the class of complement therapeutics to treat severe autoimmune disorders. Our lead program, DNTH103, is a perfect example of what we mean by next generation. It's a very potent monoclonal antibody that targets the classical pathway uniquely, the lectin and alternative pathways intact, and it is only the activated form of C1s. And the whole idea is to deliver the kind of efficacy we've seen with C5 inhibitors in various severe autoimmune disorders, such as myasthenia gravis, but to be able to then deliver that in a infrequently dosed auto-injector, low-volume, self-administered therapy.
We've already shown through our phase I data that we revealed last year that we do indeed have a very potent monoclonal antibody. It has a nice, healthy, long half-life, 60 days, because partly because of the YTE half-life extension modification made to the antibody to support infrequent dosing, and that it potentially can have that differentiated safety profile because it leaves lectin and alternative pathways intact. We are now in two phase II programs. We started our first phase II program in myasthenia gravis earlier this year. We've started the second phase II program was in multifocal motor neuropathy, or MMN, and we are now in the last steps of initiating our third program in CIDP, which we'll announce later this year.
Again, the whole point here is to go after diseases where we know the classical pathway is the pathway within the complement system that's activated by the disease, that needs to be shut down, and deliver the efficacy that you expect from complement therapeutics, but leaving the lectin alternative pathway intact so they can do what they're supposed to do, which is fight against the risk of infection from encapsulated bacteria. The whole point is to really get the efficacy, but avoid the risk of infection and avoid getting a boxed warning on the ultimate label when we commercialize.
All right. You know, so the shares have had a great run year to date. You know, what do you believe has been some of the key events that sort of have driven investor interest, and in your program?
I would say there are three things. One is our team's execution. You know, in a space of really just over 2 years since we came out of stealth mode and announced our Series A for $100 million as a private company, we've gone public. We've started and completed a phase I study. We've already stood up 2 phase II programs. We're about to stand up another third major program with CIDP. I think the execution, the delivery, the continuous confirmation that we really are on track to deliver on our target product profile of that, you know, infrequently self-administered through an auto-injector complement therapeutic with 103, I think has been a real confidence booster for investors.
I think secondly, we've been very lucky in that our competitors have helped de-risk and provide the proof of concept for our active C1s inhibitor. argenx, with their C2 inhibitor in MMN, have shown great efficacy, and they have themselves confirmed that it's really driven through their blocking with their C2 inhibitor of the classical pathway, not the lectin pathway. So that's de-risked our MMN program, but probably more significantly was Sanofi with their active C1s inhibitor in their pipeline, where they revealed really impressive significant efficacy in CIDP with their active C1s inhibitor in their phase II open label trial. That's the first time a complement inhibitor has been shown to, you know, have efficacy in CIDP, and it's actually the first time an active C1s inhibitor has been shown to work in any neuromuscular type condition.
They revealed very impressive data versus IVIG in patients who are stable, patients who are refractory to IVIG, as well as treatment-naive patients, and so that's really helped de-risk that indication as well for us, and I have to say that was also part of the catalyst for my third point, which is that we had a really impressive PIPE set of investors, new and existing investors, come into a PIPE earlier this year for $230 million, so now we're really very well funded to the second half of 2027. We've guided in terms of our runway, which gives us a, you know, significant runway beyond our first major data catalyst, which will be our MG phase II results in the second half of next year.
So I think the combination of those three things, our execution, you know, and obviously the antibody we have, the external catalyst from our competitors, as well as, you know, the extension of the runway and taking any kind of financing overhang away from our first data catalyst, I think have really helped build confidence in the stock.
... You know, you mentioned coming out of stealth mode, and, you know, I'm not sure if you can comment or would like to comment about it, but, like, I think it's important that people understand where this molecule came from, and it wasn't something that just fell into the lap. There was actually strategy behind it.
Exactly. The Fairmount Funds team have had a tremendous run of success, especially now through their incubator, Paragon. But before Paragon existed and earlier in Fairmount's life, they were sitting around, and they saw really fantastic data from a C1s inhibitor in Sanofi's pipeline, which was sutimlimab, Enjaymo, in cold agglutinin disease and in ITP, two hematological indications. And it was the first time that you saw really impressive efficacy from a classical pathway inhibitor with that potential to reduce the risk of infections from encapsulated bacteria. So, the issue with Enjaymo or sutimlimab, which is approved and on the market today, is you have to deliver six thousand five hundred to seven thousand five hundred milligrams through an IV every two weeks. That's a huge amount of drug.
And so the Fairmount team, with consultants, looked at, well, how could we deliver that kind of efficacy targeting the classical pathway or C1s, but at a much lower volume, so you could put it into an auto injector in a subcu form? And that's where the idea of going after the activated form of C1s, which is much less prevalent than the pro form, which is what sutimlimab also binds to. So there's a huge amount of drug given with sutimlimab. A lot of it is wasted on inert proteins. The idea is go after the activated form of C1s, which is what's really implicated in the cascade and, you know, what triggers the classical pathway and eventually leads to the formation of the MAC.
And that's how 103 was designed and born.
Excellent. Thank you for that background. And so let's. Like you mentioned, you're in the clinic with two, and you're about to enter with a third. You know, what drove the decision to actually move into MG as your first indication?
You know, when you look at the MG market, there's many reasons to go after that first. First, it's a blockbuster market that already supports multiple blockbusters. You have the C5s, who are as a franchise, selling over $6 billion annually. They're still growing. That growth is coming from MG, biologics-naive patients in the U.S. So, you know. And then you have, of course, the success of efgartigimod. It's over 100,000 now, some estimates, in terms of size population in the U.S. So, it just has a lot of favorable commercial dynamics. And then when you look at 103 , it's very clear that it could be a differentiated best-in-class within the complement class therapy, because the only complement therapies approved or in development outside of 103 are C5 inhibitors.
They're all terminal inhibitors of the complement cascade. They're all going to have boxed warnings around the risks of infections. From a commercial standpoint, it's definitely the biggest opportunity we have with a classical pathway inhibitor like 103. And then when you look at risks in terms of development risk, regulatory risk, it's very clear the path we have to take. It's a 12-week study, our phase II study, with 20 patients per arm. The phase III will be the exact same design of this phase II, just larger numbers to move the MGADLs to a primary endpoint. We know exactly what we need to do in order to get to a successful BLA and launch within MG. That came out far and above the best, as a best opportunity.
Since then, of course, MG and CIDP have been added because they're also very significant opportunities. Within CIDP, again, we could be the active C1s inhibitor from Sanofi, showing fantastic efficacy. We have a better antibody. We have a more potent antibody that could be dosed much less frequently and lower volumes. And with MMN, you know, there's only a C2 inhibitor from argenx right now ahead of us, and no FcRn will be developed in MMN because it won't work. It's an IgM-driven disease. So those were picked as the next most exciting opportunities for reasons where we could differentiate ourselves very well. And so those are the three that we started. And the nice thing, again, with these three, is they're all neuromuscular indications, so there are very clear clinical synergies.
A lot of the KOLs, a lot of the investigators, a lot of the sites are the same places.
Mm-hmm.
So we can leverage. We kicked off the MG. We can leverage that trial and our relationships and the sites to for MMN, as well as later for CIDP. And then, of course, from a commercial standpoint, there's clear synergies. To have just one neuromuscular-focused footprint, for example, in the U.S., to go after, and you know, educate physicians and so on. I think there's just very clear synergies to the way we've approached the three indications.
All right. In terms of evidence, sort of what gives you confidence that going upstream in the classical pathway will lead to you know, comparable efficacy or even differentiated efficacy? You know, as you mentioned, there's a lot of downstream inhibitors, C5 inhibitors, terminal inhibitors that have shown great efficacy. Why go upstream, and what is, like, the neuromuscular KOL community, actually, how they align? What's their perspective?
Yeah. Look, I think if you spoke to most KOLs in the MG community, and you review the literature and the science behind it, it's actually a pretty well-defined rare disease, and it's quite often referred to as a classical pathway disease. I think, you know, it's very clear that it's an antigen-antibody complex that's causing the damage at the neuromuscular junction that's triggering the classical pathway, and so for us, the biological rationale is very clear. We also have an experiment in our corporate deck, where we looked at an in vitro experiment, a well-known sort of human-on-a-chip model from Hesperos, a vendor that we worked with.
You very clearly see in that experiment that we have a very similar signal to C5s in that experiment with MG patient sera. Look, I think from a biological rationale, from a scientific rationale, it's well understood that MG is a classical pathway disease, so it logically would make sense that then just shut down the classical pathway, leave the lectin and alternative pathways intact. They don't seem to really have a role. We'll see if that thesis is correct in the second half of next year when we read out the phase two data.
Everything seems to indicate from the in vitro experiments, from the KOL feedback, from the reception we're getting from investigators and their enthusiasm in participating in our phase two trial, that, you know, we should be on the right track.
Excellent. You know, and, you know, just if you could provide some thoughts on the proposed, like, C5 bypass mechanism. I'm sure you may be familiar with it, you know. Is there anything that, you know, perhaps going more upstream, you may see a differentiated efficacy-
Yeah
profile because of that bypass mechanism? I mean-
It's an interesting theory. We are not expecting to see the impact of any potential benefit of being an upstream inhibitor versus a terminal inhibitor in a short, what, twelve-week trial with scales that are, you know, very much, you know, qualitative scales.
Yeah
...whether, you know, quality-of-life-type scales. I'm not sure we're gonna see that kind of difference in those short trials. There may be the ability to flesh that out and see if there is a benefit in the longer term versus a terminal inhibitor, but I think we would be... I certainly would be very, very happy to show similar efficacy to a C5 inhibitor like Ultomiris. It-- to me, that's the gold standard efficacy for any biologic. You have something where you see very clear efficacy. There's no need for having to stop dosing and cycle patients and letting their symptoms rebound. You stay on it in the long term. All the data we're seeing from the real world and what's being published out there is that the efficacy continues to improve even over the longer term.
Mm-hmm.
That's not something that's been shown with FcRns. I think if we're gonna show similar efficacy to Ultomiris, I'm very happy because then we win on differentiation from a dosing convenience standpoint.
Yep.
We win on a safety standpoint, and then I think it just makes it clear that we're a best-in-class biologic for MG patients.
All right. You know, talking about the phase 2 MaGic trial, it's underway, data expected in the second half of next year. You know, just you're evaluating two doses, 300 and 600. The 300, the IC90, you know, is the... You reach above IC90. You know, so why move to the higher dose? You know, do you think you may leave a little bit of efficacy on the table or?
Yeah, look, I think 300 milligrams every two weeks, you know, we're, we're getting significantly above the IC90 target in humans, and that is significantly shutting down the classical pathway, and we feel that that's enough to get whatever efficacy we're gonna see for 103 in MG. It's a phase 2, and we said: Well, you know, typically, you have some dose ranging. And certainly, the question we haven't answered is, well, what happens if you get above IC95, like, way up there in the levels of inhibition? And we know with 600 milligrams every two weeks, we get, you know, even higher levels of inhibition. And so we said: Well, why not? Let's perform the experiment.
That question's never been answered with a classical pathway inhibitor, and we as a team fully expect that the efficacy is going to be the same. I don't think we're gonna see additional efficacy. I think once you get above IC90, you're doing everything you need to control the symptoms and conditions like MGADL with MG patients, like on the MGADL scale.
Okay. I mean, even though we're not done with MG yet, do you think same concept with CIDP and MMN?
I think so. I think it'll be the same, but, you know, again, just to remain consistent, we're testing both doses in MMN, and later this year, we'll reveal the program with CIDP.
I thought you were gonna reveal the program here.
Yes, I really wanted to, Pete, but my team didn't let me.
All right. MaGic trial, it's 60 subjects. You know, the study's powered to show efficacy, is not powered, right?
No, no. So look, this is probably the largest phase 2 trial done with a complement inhibitor. Others have had smaller ends-
Yeah
... and have still had a significant p-value, even though the MGADL is a secondary endpoint. Again, this is only N 20. It's a phase two. It's powered for safety, tolerability. That's the primary endpoints. But I think if we get anywhere above a one point five, let's say, improvement on MGADL versus placebo, above that, we should have a positive p-value.
All right.
That's our expectation, is to be, you know, somewhere north of 1.5 difference on MGADL versus placebo.
All right. And then, and so that's what defines our success in terms of facilitating movement forward into-
Yes.
All right. All right, so I guess, you know, one of the important factors, you know, when you run a clinical study, is, you know, who's sort of at the helm of clinical development. If you do actually go, you know, on your website and you look, you do have someone there who I think, you know, helps... may help de-risk the program-
Sure
... just because of experience. So just a quick, brief synopsis of this individual.
... I'm assuming you're not talking about me, right?
You know-
I am so proud of my clinical team. One of the things I'm most proud of, actually, as I mentioned earlier, is the execution, and that is all, you know, with Simrat Randhawa, Dr. Simrat Randhawa, our CMO, and the team under him. You know, this team has experience with MG like, for decades, within the autoimmune space, and have successfully taken other programs all the way to market. I think you're probably referring to Dr. Gokhale, who is our Senior Vice President, Head of Clinical Development, Neurology. He is a board-certified clinical neurologist, passionate about MG. Had a tragedy within his own family, with someone dying from MG, actually. He actually led...
It was part of the team or led the MG Ultomiris program at Alexion. He also was involved with leading the Soliris pediatric program at Alexion. So his knowledge of the investigators, the sites that were, you know, most productive, that, you know, all the the secret sauce to a successful recipe in in delivering a successful phase II, phase III program in MG, you know, he's been a really fantastic asset for the company. And he is very much, you know, sleeves rolled up and hands-on in ensuring that we are successful with this program in terms of execution, in terms of, you know, making sure we get good, high-quality data at the end of the day.
and so whatever 103 can do in MG, we're gonna see it with this program. I'm very confident. I, I'm very confident there won't be an issue in terms of execution. It'll all be about the biology and what the antibody can do.
Yes. Yes, I was referencing him, but you do have,
I, I-
- other individuals.
I'm disappointed it wasn't me, Pete, but maybe next time.
But you, you're responsible for hiring.
Thank you. There you go.
All right. So, moving on to CIDP, you know, with the caveat of being a non-placebo-controlled study, you know, what are your thoughts or your team's thoughts on the real-world data? You know, especially improvements observed in the standard of care and standard of care-refractory patients.
You know, the riliprubart data was actually one of those, you know, few turning points in our life as a company. What's most impressive, they just updated the data at PNS in Montreal at the end of June.
I was there.
You were there, right?
Yeah, and I...
You know, they had an update and increased the N, but it's still interim data. But as you mentioned, what really intrigued us, what we thought was most powerful about that data was that IVIG is seen as a gold standard in CIDP.
Mm-hmm.
They took patients who were stable on IVIG and doing fine and switched them to active C1s inhibition and as of the data presented in June, 52% of those patients switched, actually improved further on active C1s inhibition. Now, if you think about what that means, the other class that would be competing for first-line use in CIDP are FcRNs. FcRNs and IVIG have a similar mechanism of action.
Yeah.
I would not expect if IVIG, if you're on the proper dose and you're tolerating it and it works, that switching to an FcRn, you would get any additional efficacy. You should get similar efficacy. But yet, with this active C1s inhibitor, over half the patients actually improved. And then, they also took a group of patients who were refractory to IVIG, switched them, and also half those patients improved on active C1s inhibition. To me, that's a very interesting efficacy signal. Is there something about active C1s inhibition that is more beneficial for CIDP patients and can deliver potentially improved efficacy over IVIG, which is considered the gold standard therapy today? It's an open label, no control. I mean, there's all those caveats, so we have to be careful.
But, that kind of efficacy, quite honestly, was what triggered this PIPE that we were able to execute late, earlier this year, was a major factor. So, we look at that and we say: "Okay, this has pretty much de-risked the program for us.
Yeah.
Now, we just need to go into and, you know, deliver on the promise of 103 versus riliprubart.
Yeah. Doing well is a relative term, you know, and, you know, many times patients, you know, they readjust, you know, sort of their perspective on what well is, you know?
Sure.
The physicians do.
Yeah.
You know, I have a brother-in-law who's a practicing neurologist and, you know.
Yeah
... a little bit better, you know? But-
Yeah
... efficacy is obviously left on the table with IVIG, I mean, in terms of...
Sure.
Yeah.
I know. I mean, there are some KOLs who think there is no efficacy, additional efficacy you can get, and yet, look at this data. So yeah, look, one of the great benefits of our industry is sometimes you get to work on next-generation therapies that can totally redefine what the gold standard is, could totally redefine what a successful outcome is.
Yeah.
That's what we're most excited about. We really think 103 could potentially deliver on the promise of redefining what getting your life back is for an MG patient, MMN, or CIDP patient. That convenient- that delivering the efficacy with a lower safety risk and the additional convenience of an auto-injector, I mean, look at what's happened with GLP-1s. If you can, you know, have a seven-second auto-injector, you can just give yourself in the abdomen or on the thigh very, you know, very quickly, every two weeks only, I think that would be a game changer for patients, not having to, you know, schedule their life around their infusions or therapy.
Absolutely. Last question, I'll ask you-
Sure
... really quickly, and we're actually running out of time. I would've liked to get through MMN. I know you can't fully answer, but, you know, what's your expectation or would like to see in terms of conducting a single study for an approval in CIDP?
You're trying to get me to announce something ahead of time. We'll have more information on that later this year, but we're very excited about CIDP. It is our third indication, but I know there's a lot of attention on it. I think one of the things we did earlier this year that provided a lot of comfort for investors, knowing that we're on the right path, is we also revealed head-to-head data. We've, you know, various experiments we conducted in vitro versus riliprubart, the other active C1s inhibitor, just to give comfort that we have a better active C1s inhibitor in the sense that it's more potent, and therefore, we could deliver lower volumes less frequently than riliprubart, which is 600 milligrams, 4 milliliters every week, versus our 300 milligrams, 2 milliliters every two weeks.
So if you were to put those into auto-injectors, essentially it's two shots of DNTH103 versus eight shots of riliprubart. So that's a significant reduction in burden for patients if they were to be delivered in auto-injectors. So I'm really eager to reveal the strategy we have behind CIDP. I promise you it'll be before the end of this year. That's our goal.
All right. Do you have time for drinks tonight?
No.
Yeah, one more thing.
Oh, sure.
All right, we got two minutes left. Quick thought on MMN.
You know, MMN, is sometimes, a little bit, in the shadow of CIDP because there's been so much data generated by Sanofi and, of course, MG, because of this huge blockbuster potential. But we have to remember, yes, it's a smaller, rare disease, but it's one where FCRns don't work, and it's IGM driven, and a classical pathway inhibitor is exactly what you need in that disease. And right now, our only real competition is empasiprubart, which is an IV that has to be delivered every week or every two weeks, that also blocks lectin, and blocking lectin has no benefit for MMN patients. All it's going to do is add potential safety risk, potential infection, risk. I would be surprised if that didn't end up with a box warning-
You just answered my question.
... like every other complement therapy. So again, the same advantages we have versus the C5s and MG, we will have versus empasiprubart in MMN. There's nothing like our antibody being developed in MMN, and those, I think that's a market we will have to ourselves. So yes, smaller pie, but we'll get a much bigger piece of that pie.
Great. Last question. If we're sitting here 12 months from now, what would you like to say were your value creating accomplishments?
That's a good question, Pete. 12 months from now, we could be, if not already announced, very close to announcing our MG data. I think that's going to be a big moment for us, of course. That'll be the first time we show data in actual patients.
Yeah.
I think, you know, that will be it. That's 2025 for us.
All right. And a path forward for CIDP.
No, of course, of course. But we will have, we will have that this... That'll happen this year-
Yeah
... for sure.
Okay. Well, thank you very much for attending our conference-
Thank you for the opportunity, Pete.
Conversation.
Thank you.