Hey, welcome everyone. Thanks for listening in. I'm Gavin Clark-Gartner, one of the senior biotech analysts here at Evercore ISI. Really happy to be joined with Marino Garcia, who is the CEO of Dianthus Therapeutics. Thanks for joining us, Marino.
Thank you, Gavin, and thank you to the Evercore team for having us here and this opportunity to update everybody on the great progress being made by the team.
Absolutely. I'll just kick it over to you for an overview of the company, where things stand today, and then we'll run into some more specific questions.
Sure. So this year was about execution on three clinical programs in three different indications. So we started the year with kicking off our MG trial, phase II trial of DNTH103 versus placebo, two different doses, our 300 and 600 milligram subcu every two weeks. That trial is going according to plan, and we are still on track to put out top-line results from that phase II program in the second half of next year. Subsequently, we kicked off the MMN program, phase II program, and have started recruiting patients. And that is also still on track to data in the second half of 2026, so a year after MG. It's a more complicated, longer trial, rarer disease, so it's just going to take a little more time.
Then the most significant recent news, I think most people were expecting us to then kick off a CIDP phase II program before the end of this year. In our Q3 release earlier in November, we announced that we are actually moving forward directly into a phase III pivotal program. The rationale, the reasoning there is we were very carefully watching what Argenx did with their novel ADHERE program, their CIDP program for efgartigimod, and saw that at the end of June, they were approved with a very broad label indicated for all adults with CIDP. That, to us, was a major success on their part, and we wanted to replicate that. We essentially are moving into an ADHERE-like trial, which is a two-part phase III program with two important differences. Part A is similar.
It's open label, where we test CIDP patients on 103 every two weeks, up to 13 weeks, and if at any point they respond during that time period, we then immediately randomize them into a part B blinded portion of the trial. That second part will take up to 52 weeks, but there are two important differences I want to point out from the ADHERE trial. One is there is no screening period where we force CIDP patients to come off of IVIG or standard of care and deteriorate. That's something we've heard very clearly from physicians and patients, is something they really dislike and would be an impediment to recruitment, so we are not doing that, and secondly, we are allowing patients who are refractory to standard of care or IVIG or subcu IG to enter into our trial.
That's because when we saw the riliprubart active C1s inhibitor in Sanofi's pipeline, when we saw their data, they showed very strong efficacy signal in patients who were refractory to standard of care of IVIG. So there's no reason for us to take them out of our program, as we do expect a significant portion of those patients to respond to active C1s inhibition with 103. That's in terms of our three indications. That's the broad update. We also announced that we had about $343 million in cash, which would take our runway out to the second half of 2027, allowing us to read out the phase II MG, the phase II MMN. Then at some point in the near future, we'll give a little more details around the timelines for the CIDP program and what part B would look like.
Awesome. That makes sense. One quick clarification. You do have an IND cleared for CIDP.
Yes. So I should have made that clear, right? We have agreement with the FDA to move forward into a pivotal phase III program with DNTH103 and CIDP. Yeah.
All right, great. And more of these details might come out later this year, early next year. So tell me if I'm jumpstarting or getting a little ahead here. But just on the CIDP trial design, without including the, or I should say, the lack of deterioration period within kind of part A of the trial, do you think that'll impact the response rates at all in any way?
I don't think so. You look at the riliprubart phase II data and you see how robust the efficacy was with riliprubart in three patient groups: patients who were treatment naive, obviously, but also patients who were refractory to IVIG and patients who were doing fine on IVIG and switched without a washout, long washout period and waiting for patients to deteriorate. You still saw, specifically in the refractory and patients who were stable on IVIG, 50% or greater response rate when switched to active C1s inhibition. That clearly tells us there's no need to make patients go through that. And I'll tell you, it would impact recruitment. I think we've had other companies also point to that as a reason for delays in their CIDP readout. It's just something that's very clearly not needed, we believe, with DNTH103.
That makes sense, and one of the other bigger picture questions with this study is, did you ever consider running a head-to-head versus IVIG study since Sanofi with riliprubart is running two, one of them being a head-to-head versus IVIG? What did you think about that? Why did you decide to do an ADHERE-like study?
So Sanofi is doing two phase III studies. They're both placebo-controlled. Their phase II is an open label, not placebo-controlled. And it's their first indication. So you do have to have two placebo-controlled trials to go to the FDA with your first BLA. One is a superiority trial versus placebo and refractory patients. And the IVIG study, which you mentioned, is a non-inferiority. That's a perfectly valid approach to getting to a BLA. What we really liked about the ADHERE approach, if you like, the approach that we're taking, is there is really no way to have a higher probability of success of getting to a successful outcome in a BLA.
And the fact that Argenx with efgartigimod got this broad, all adults with CIDP with this design, I mean, to me, that just means strategically it's the way to really get to the maximum probability of success you can in biotech for a successful supplementary indication, for a second indication. So when we look at the data from riliprubart in their phase II, as I mentioned, those two patient groups, you have patients who are refractory to IVIG, switched to active C1s inhibition, and you see 50% improve. That's not something you would expect an FcRn to be able to do. When you see patients who are doing fine on IVIG and still over 50% when switched to active C1s inhibition improved further, that kind of signal seems to suggest that active C1s inhibition may be superior to IVIG.
If Sanofi is able to show superiority in their non-inferiority trial, that would be a huge home run. I think that would have a very clear positive halo effect on us because from our trial, we'll also be able to look at the subgroups and let you know how we did in those refractory patients as well as patients who are stable and then switched to active C1s inhibition. And when you take the totality of that and you realize and you understand that we have a more potent antibody that results in much more favorable dosing administration, I think that'll be very positive for the class. And it's clear we have the best in class. So I think that would be really great news for everybody. If at some point my commercial person, when we hire a commercial person, tells me later, "Hey, you know what?
It'd be good to do a head-to-head study versus IVIG." Sure, we'll do that. But right now, this study is, I don't want to say guaranteed, but it's about as high a probability of success as you can get to a successful BLA. And Argenx, kudos to them for the job they did. And we're just going to replicate that with those two changes I mentioned.
That makes sense. And thinking about the ADHERE study, how long did that take to enroll? How much faster do you think you can get that done?
It took a while to enroll. It was a large study. I think we haven't given any indication yet on timelines. As I mentioned, in the near future, we'll give a little more details around what part B looks like. We have the IND cleared. We're just working through some dotting i's and crossing t's with the FDA. So once we're ready, we'll divulge the details of what part B looks like, and then we'll give a little more guidance around timelines.
Yeah, that's fair. That's fair. Thinking bigger picture too, what did you guys make of the Vyvgart pricing in CIDP? I know it was higher than many investors anticipated. And specifically, how does that fit into your multi-indication strategy? It's a broad question.
No, it's a great question. I can't wait to put that to my chief commercial officer in the near future. No, look, the only reason they have that pricing difference is because they have intermittent dosing, right? Personalized dosing, I guess they call it, in MG. But in CIDP, it's continuous dosing. So logically, it'll be more expensive. Frankly, that also seems to work when you look at the size of the opportunity, right? MG now, some estimates are that in the U.S. alone, you're looking at over 100,000 patients. And with CIDP, it's maybe approaching half of that size. So it's not surprising to me that CIDP could potentially tolerate a higher pricing. So that's something we're very cognizant of.
We will be looking at how we price 103, what does the dosing look like in the different indications, and take a holistic sort of portfolio strategy approach to it. But right now, it's a little early for us to talk about pricing. It'll be very interesting to see where riliprubart prices when they get approved. I'm sure they will in CIDP. It'll be very interesting to see where empasiprubart, the C2 inhibitor in Argenx's pipeline, prices when they get approved for MMN. They're also going into CIDP there. So they'll have to think about also a portfolio pricing strategy. So we'll have a lot more information before we have to make any final decisions on pricing.
Great. Switching gears, going over to the MG study since that'll be a big proof of concept readout next year. Maybe a place to start for this one, maybe just kind of comment on expectations for the data, including patient population that's been enrolled in prior FcRn use.
We are allowing patients who have been on FcRNs before or IVIG, et cetera. The only patients we're excluding are patients who have been on complement therapy in the past. Look, the patient population will be very similar to what you've seen with other complement therapies in phase IIs or phase III programs. My expectation is to achieve similar efficacy to the gold standard, which is Ultomiris. We are aiming for 103 to be the best in the complement class. So that means achieving similar, if not better, but similar efficacy at least to Ultomiris and having that on our label. And I think their efficacy numbers were somewhere around 1.6, 1.7. I think once you're in the high ones, approaching two, I think that's a win on efficacy.
Our goal, if you like, when you think about the label for 103 eventually in MG, is to cut and paste the efficacy profile from Ultomiris and improve label, put that in, take the dosing administration label from Dupixent, cut and paste, put that in, and then take the safety and tolerability profile from Enjaymo or sutimlimab, the first generation C1s inhibitor that's out there approved for cold agglutinin disease, take that and put that on our label. I'd be very happy to get their safety and tolerability profile. It's the only complement therapy on the market with no box warning around any safety issue and no REMS program. And that's with a C1s inhibitor that's dosed at 25 times the dosing we're going to be giving with 103.
Taking the combination of those three different labels, those different parts of those three labels into one, I think is really what we're aiming for with 103 and MG.
Yeah, that makes sense. And I know you guys are not setting this as your base case expectation, but I'll throw it out there that there are a few interesting lines of evidence that suggest upstream complement may be superior to terminal complement inhibition in terms of efficacy. And it may depend on disease, et cetera. But any thoughts you can share on that front?
Look, there's already papers out there looking at real-world evidence that seems to suggest that C5 inhibition may be in the longer term superior to FcRn inhibition. There's one specific PANE, the PANE that was published and presented at AAN in June that looked at real-world evidence in Italy specifically that seems to suggest that. The next step is, is there a potential for better long-term efficacy than C5 inhibitors? What you're getting at is upstream inhibition. Maybe that could have some benefit. What I can say is I don't expect that in a 12-week period. That's a short study. That's all the FDA requires. Is there potential for that difference in the longer term versus terminal inhibitors? Potentially, but I don't think we will see that in 12 weeks.
We may see that over a year in the longer term and maybe in the open label extensions, et cetera. But it's an interesting theory. But again, the bar, the goal here is at least in a 12-week study be similar to Ultomiris. People consider that a gold standard in terms of efficacy in MG. Patients love it. Physicians love it. If we can achieve that with all the other benefits we bring to the table for MG patients, I think that's a major win.
Got it. And thinking about the sequencing of CIDP and MG, and some of these details may be still to come out, so I might be a little early here. But if CIDP you're going right into a registrational study, it is a little longer. But MG, you're in phase II now, presumably moving to phase III after. How much can you accelerate? And what does the launch timing sequencing look like there?
Yeah, we haven't given guidance on timing for launches or approvals. But what I can say is MG, we expect to be the first BLA and the first indication. And that CIDP will come closely behind it. And that's partly why we can get away with only one placebo-controlled trial for CIDP. So we are still looking at MGs being our first indication, and then CIDP MMN close behind.
Got it. Another question that I forgot to throw in there for thinking about the MG data back half of next year. What are your expectations on the ANA titer elevation component? It's something we've spoken about a lot in the past, but probably worth framing that.
It's very difficult to not have patients who are ANA positive coming into these trials. They have autoimmune disorders, so they will. It's something we're monitoring. It's obviously an adverse event of special interest that we'll monitor. And that's true for every complement inhibitor. All I can say is we had two patients in our phase I or II healthy volunteers, I should say, in our phase I who started ANA negative and ended up being positive for ANAs at day 57. But both had no symptoms of any autoimmune disorder or SLE. Both were evaluated. Both were negative for double-stranded DNA, which is a more specific marker for lupus. And that's happened also with Ultomiris, sorry, not Ultomiris, sutimlimab, the first generation C1s inhibitor, and riliprubart. And they also had placebo patients who were ANA positive. So it's something we're monitoring. We're not terribly concerned about it.
Certainly, the good news is that at least with the three C1s inhibitors, the first generation C1s inhibitor and the two active C1s inhibitors in development, there have been no patients to date in market or in development clinical programs that have developed any SLE-like symptoms to date, so.
Yeah, got it and quickly touching on MMN, I guess I'll probe one question is if you could do a single registrational CIDP study, is there any chance MMN could be one study? I'm well aware that Argenx set the precedent of doing phase II to phase III, so it's probably not a great base case but what do you think on that front?
Yeah, I mean, there's been no precedent. We don't even know what the FDA, I don't know if the FDA knows what they would expect from a pivotal phase III program yet. So we're very eagerly watching what Argenx is going to announce with their empasiprubart when they announce their phase III program in MMN, I believe early in the new year.
Yeah, that sounds great. We're actually just at time, so maybe I'll turn it over for any closing remarks as we head into a very exciting 2025.
Yeah, no, I just want to say I'm really, really proud of the team. It's been a heavy lift. We started the year thinking three phase II programs, and now here we are already phase III company. And yeah, they're doing a phenomenal job. And I am very excited to see the MG data in the second half of next year. It'll be the first time a classical pathway inhibitor has been studied in MG. It'll be the first time we see what upstream inhibition can do. And obviously, for us, it'll be an incredibly important moment. Every year we seem to have important moments, but this one is really going to be exciting.
Absolutely. Looking forward to it. Thanks for joining me, Marino.
Thank you, Gavin.