All right, I think we'll get started. So thank you again for coming to TD Cowen's 44th Annual Healthcare Conference. It's my pleasure to introduce to you Marino Garcia, President and CEO of Dianthus Therapeutics. Take it away.
All right. Thank you, Brandon. Thank you to the TD Cowen team for this opportunity to present today on behalf of the Dianthus team. Why don't we get started? Just a quick reminder, I'll be making some forward-looking statements, so I direct you, please, to our SEC filings on our website for any risk factors and other information. Dianthus was founded in 2019 with the idea of developing next-generation complement therapies to treat severe autoimmune disorders. What do we mean by next generation? Our lead program, which has now just begun its phase II, is a potent DNTH103 investigational monoclonal antibody that targets the classical pathway uniquely within the complement system by targeting or inhibiting only the active form of C1s.
What that allows us to do is to potentially deliver a very effective therapy in a low-volume, subcutaneous, infrequent self-administered injection, and with the target of delivering this every two weeks with our first indication in generalized myasthenia gravis, the phase II program we've just announced recently has begun. We recently reported out our top-line phase I data in healthy volunteers, which confirmed that we had a nice, healthy 60-day half-life, which will allow for that infrequent dosing, a very potent profile in terms of inhibiting the classical pathway, as well as a potentially differentiated safety profile.
In addition to our own data, there's been recently also additional data from other complement therapies showing proof of concept in conditions such as CIDP and MMN, the other two indications we're going after, really confirming the role of complement in these various neuromuscular conditions as well as the pipeline and a product potential for 103. So as I mentioned, we've now initiated our phase II program in generalized myasthenia gravis in the first quarter of 2024, for which we are anticipating seeing data in the second half of 2025. And we're also on track to initiate the two other indications to other neuromuscular phase II studies in MMN and CIDP this year. And we recently completed a $230 million PIPE, which allowed us to extend our runway out to the second half of 2024.
As I mentioned, one of the things that's very exciting about DNTH103 is that pipeline and a product potential. And on top of that, the ability to potentially be a best-in-class complement inhibitor in these various indications. The three first indications we're going after are all neuromuscular conditions, which have really clear, nice synergies across the three from a clinical investigator standpoint, from a KOL standpoint, from a clinical site standpoint, as well as, obviously, down the road, commercial synergies. The first is generalized myasthenia gravis. It's clearly a $multi-billion autoimmune rare disease market where there's still a role for a highly differentiated complement inhibitor like DNTH-103 to expand on first-line biologics use. CIDP, chronic inflammatory demyelinating polyneuropathy.
Recently, there was exciting data from Sanofi's phase II active C1s inhibitor showing very clear efficacy signals in both patients who were stable on therapy and switched, IVIG therapy and switched, as well as refractory to IVIG therapy. And then finally, in multifocal motor neuropathy, again, a smaller market but one where FcRns wouldn't potentially show efficacy. And there we had another competitor, argenx, a C2 inhibitor that has to be dosed through an IV on a weekly or biweekly basis that showed very clear efficacy signals from our argenx pipeline. And again, that's all about the classical pathway inhibition. So these are very, very exciting multiple indications where there has been proof of concept and where we're developing 103 to build a very strong neuromuscular franchise.
As I mentioned, we've begun our MG phase II trial this year, and we are on track to start two other phase IIs later this year. So this year, really, for the Dianthus team is a year of execution. It's a year of really focusing and getting DNTH103 started in multiple indications in patients. And our first data readout, as I mentioned earlier, is with myasthenia gravis in the second half of 2025. So digging down a little bit into more detail in myasthenia gravis, GMG is a multi-billion dollar rare disease market where there's an opportunity where there's only two approved biologic classes, first-line biologic classes, FcRns and complement, but where there's still a significant room for improvement. So if you look at the U.S. market alone, that's about 60,000 patients addressable with first-line biologics.
Within the complement class, you have Soliris and Ultomiris, a franchise that's selling now over $6 billion a year. About a third of that is in neuro indications, and they've recently indicated that MG is really their main growth driver. And on top of that, it's around patients who are naive to biologics, so first-line use. So again, still showing tremendous growth in that franchise. And then the other class, of course, the FcRns with Vyvgart , which in its second year has already achieved blockbuster status with over $1 billion in revenues last year, where again, most of their sales is with their IV presentation. So again, two classes, two first-line biologics classes, our goal is to be the best in class within the complement. And how would we compare to these approved therapies that are out there now in the complement and FcRns?
We can see that with our target product profile of delivering a low-volume, subcutaneous, infrequent, every 2-week self-administered autoinjector, how that could really maximize patients' convenience and reduce the burden of treatments on them. The most successful products right now are at the bottom. You see that with Soliris, Ultomiris, and Vyvgart. Those are IVs that have to be given in an infusion center, obviously, by healthcare professionals. There've recently been some Sub-Q versions of FcRns and a C5 inhibitor that have been approved, including the first self-administered therapy in the U.S., Zilbrysq, or zilucoplan, a C5 inhibitor from UCB. Unfortunately, that's a daily injection that patients have to give themselves every day. So again, there's nothing on the market, nothing approved, that comes close to the kind of profile that DNTH103 could deliver for these patients.
Now, digging down a little more into the rationale, the efficacy portion, we already know that complement inhibitors are very well established in GMG and other severe autoimmune disorders. We all know that GMG or myasthenia gravis, as well as MMN and CIDP, are very much complement-driven diseases, classical pathway-driven diseases. Our idea with 103 is to go after the classical pathway, inhibit only the classical pathway, as opposed to terminal inhibitors like the C5s, like I mentioned, Zilbrysq , Ultomiris, Soliris , who inhibit the formation of the MAC at C5 and therefore have box warnings around the risk of infection from encapsulated bacteria. So you see on their labels, you will have a box warning around the risk of meningitis, for example, and an associated REMS program.
With C1s, by going after that target, which there is an approved therapy for, and Jaime will talk about in a moment, that is the first complement inhibitor that has no box warning around the risk of infections. That's because it inhibits only the classical pathway, which is what's driving the disease pathology, leaving the lectin and alternative pathway intact to do what it's supposed to do, which is fight against the risks of infection. Just drilling down a little more on C1s, the part of the classical pathway that we're targeting, C1s consists of three molecules: C1q, which acts like a carrier for two C1r and two C1s proteins.
C1q is the initial part of the classical pathway cascade that is triggered by the presence of antibody-antigen complexes, which then activates C1r, which then subsequently activates C1s, which goes through a conformational change and acts as a protease to cleave C2, C4, initiating the classical pathway, which eventually leads to the formation of the MAC or the membrane attack complex. The idea here is to inhibit at C1s because it is the only validated target within the C1 complex. There's an approved therapy, as I mentioned, with ENJAYMO. The issue with ENJAYMO or sutimlimab from Sanofi, which is approved for cold agglutinin disease, is that it not only binds to the activated form, it binds to the proform of C1s as well. For that reason, you have to deliver 6.5-7.5 grams of ENJAYMO or sutimlimab every two weeks for an IV infusion.
That's a huge amount of drug. But a lot of that drug is binding to the proform, this inert protein that's not really providing any benefit for patients. By going after only the activated form, which is much less prevalent than the proform, we can deliver a much lower volume to get the efficacy that's required and to inhibit the classical pathway. There's another active C1s inhibitor that's in development. I'll talk a little bit about that later, but it's also in Sanofi's pipeline, riliprubart, and it's being studied for CIDP. And it recently demonstrated great efficacy data in CIDP, which I'll talk about in a little bit later. So before I jump into the phase I data, the goal here with 103, when it was designed, is to exploit that C1s biology and develop the best-in-class complement inhibitor possible sorry, the best-in-class complement inhibitor, period.
So we developed 103 to have high selectivity and potency for the classical pathway, and it does have picomolar affinity, and it's that potency that differentiates it versus the other active C1s inhibitor in development I just mentioned. We engineered the YTE half-life extension technology into Fc region to extend its half-life so that we can deliver this therapy infrequently. And as we saw from our phase I data, we have a 60-day half-life, which will allow for infrequent dosing. We have the formulation to deliver 150 mg per mL or 300 mg in a 2 mL autoinjector with low viscosity, very favorable stability profile with 103, and then novel IP that will cover us for many years to come. So again, that target product profile of delivering a subcutaneous self-administered autoinjector 300 mg, 2 mL shot every two weeks is the goal we set for ourselves.
The idea was to confirm that in our phase I, which I'll talk about that in a moment. Looking at the phase I data, these are the cohorts that we completed. We had 4 IV SAD cohorts, 2 Sub-Q SAD cohorts, and then 2 Sub-Q MAD cohorts completed with 60 healthy volunteers as of the end of last year. On this graph, you can see the data. On the left, we have the 4 IV cohorts, and you can see very nice linear PK, and that's confirming that we have about a 60-day or 2-month half-life. The middle graph shows that through multiple doses delivered Sub-Q, you see nice accumulation, which allows us to then dose every 2 weeks to get high levels of inhibition of the classical pathway.
On the right, we graphed every single patient or healthy volunteer at every single data point in every single one of the cohorts. This allowed us to then determine what is the IC90 or the level at which DNTH103 inhibits the classical pathway by at least 90%. That level was identified at about 87 micrograms per mL. So we took all this data, and we graphed and modeled out what would happen if we delivered 103 every two weeks as we outlined in our target product profile. Here you can see very clearly that the steady state for 103, peak trough, is somewhere between 125 and 115 micrograms per mL. So on average, about 120 micrograms per mL. As I mentioned earlier, we know that 103 will inhibit the classical pathway by at least 90% at about 87% sorry, at about 87 micrograms per mL.
So we see a nice margin above that 87 microgram per mL target with dosing every two weeks. So this simulation is what gives us confidence that by dosing 103 every two weeks at 300 milligrams, we're going to see very robust efficacy in conditions like myasthenia gravis, MMN, and CIDP. We also obviously saw a very favorable and well-tolerated profile from our phase I data. There were no issues in terms of lab findings, no serious adverse events, no infections from encapsulated bacteria. Again, as expected, based on the fact that it's a classical pathway inhibitor only. A couple of patients had ISRs, and out of 24 that were dosed with a Sub-Q, and then a couple of patients switched from ANA negative to ANA positive at day 57. But again, no symptoms or signs of SLE, no double-stranded DNA.
So generally, a very, very clean safety profile, one that we're very pleased with going forward. So with that, I mentioned, we announced the start of our phase II myasthenia gravis study last month. This is the design. It's essentially a 3-arm study with about 20 patients in each arm, placebo, 300 mg every 2 weeks. We're also throwing in a higher dose just in case. We want to make sure we have a successful trial and we don't leave any efficacy on the table. So we're also testing 600 mg every 2 weeks. As I mentioned earlier, the data we expect to have in the second half of 2025, and if successful, and we're confident obviously that we will be, the phase 3 design will be essentially about the same, just with higher numbers.
And finally, talking about the other two indications, I mentioned earlier that riliprubart, an active C1s inhibitor in development in Sanofi's pipeline, had recently demonstrated proof of concept data in CIDP. CIDP is a relatively large rare disease market. Again, it's a nice adjacent neuromuscular condition to MG where there's no approved biologics or targeted biologics, and there's a huge opportunity for something as differentiated as 103. Riliprubart, in November, published a poster of interim data from their open label phase II trial in CIDP that showed very, very strong efficacy signals, one in what they're calling standard of care stable patients, so patients on IVIG that were switched to riliprubart. 88% of those patients remained stable or actually improved. Half of those 88%, or 44%, actually improved once switched to an active C1s inhibitor, even though they were doing fine on IVIG.
That's a really interesting and very promising efficacy signal. They also had another arm they reported out, which are patients who were refractory to standard of care or IVIG and CIDP. They were switched to their active C1s inhibitor. And again, there they saw half of those patients improve on the active C1s inhibitor, another very interesting efficacy signal. So this has caused a lot of excitement, certainly from investors as well as from shareholders and within the company, and just gives us even more confidence that we have a best-in-class complement inhibitor for CIDP. The one thing I'll note is the dosing for riliprubart.
Again, the dosing they recommended in our phase I publication, as well as the dosing they took into this phase II trial, was 600 milligrams every week, which would be about 2 injections or 2 Sub-Q injections every week versus our target product profile of 1 injection every 2 weeks. Then finally, with MMN, this is a smaller market but one where FcRns won't work. It's a complement market only, exclusively. argenx has a C2 inhibitor that they're studying in this space. A C2 inhibitor blocks both the classical pathway and the lectin pathway. So it also does impair your ability to fight against the risk of infections from encapsulated bacteria. But they showed very, very nice efficacy data at JPMorgan earlier this year that shows that their C2 inhibitor is having results or getting results in MMN.
Again, they'll tell you themselves, I think, that that is all classical pathway driven. It is an IV that has to be delivered every week or every two weeks. Again, not terribly convenient. And again, there we think we have a better option for those patients. So this is another market that we're very excited about and going forward in developing 103 for. So to wrap up, again, we are in a year of execution. We've had a tremendous last 12 months with going public through a reverse merger, two financings that now allowed us to report out $389 million on our balance sheet and cash runway out to the second half of 2027.
Now it's about getting these three phase II programs up and running in these three very, very attractive neuromuscular indications from a standpoint of where the unmet need is and how 103 could really benefit these patients and differentiate itself. We started the MG program. We'll have the results for that second half of next year. MMN is next, and then CIDP will follow soon after. Finally, I just want to say thank you to the team. We've got a really great team. It's been a fantastic couple of years of execution, which has really built a lot of confidence, certainly with our shareholders and current and new investors. We're feeling really confident about our ability to execute on these three phase II trials.
We've got a great board of directors that are very supportive and helping guide the company in partnership with myself and the management team. With that, I'll just say thank you and open it up to any questions.
Can you talk about how the Sanofi riliprubart data compares with FcRns or IVIG and CIDP?
Sure. The question is if I could comment on how the riliprubart data compares in CIDP compares to FcRns and IVIG. I think what I highlighted is what I find most interesting, is that I'm not sure I would expect FcRns to work where IVIG doesn't work. I'm not sure I would expect patients who are doing well on IVIG to be switched to FcRn and do better. What riliprubart, what I find most compelling about their data, as I mentioned earlier, is they took patients who were doing well on IVIG, switched them. The vast majority, 88%, remained stable or improved. Half of those of that 88%, so 44% of the patients they switched, actually improved on the active C1s inhibitor. This is patients who already were doing well on IVIG.
I think that's a very interesting signal of could there be additional benefit by being a classical pathway inhibitor versus just suppressing IgG levels, IgG levels. And then with refractory patients as well, I don't think I would expect FcRns to work in 50% of patients that were refractory to IVIG. I mean, it could be, but that hasn't been studied. And yet that's what we saw with riliprubart as a classical pathway inhibitor. To me, those sort of insights are what are driving a lot of the excitement within the company and certainly with me in looking at our active C1s inhibitor, which is more potent, meaning we'll be able to give lower doses, less injections, less subcutaneous injections than riliprubart in CIDP.
Alexion is developing a C1s. I'm curious if you have any thoughts about that?
The question is Alexion developing a C1s inhibitor. They're actually going after an active C1s inhibitor with an oral form. I don't have much insight there. There hasn't been that much data. All I know is they're conducting a proof of concept study in CAD, and they said they might have data by the end of this year. But I haven't seen any PK/PD data that would tell me how potent is it, how effective is it at shutting down the classical pathway. There's just not a dearth of data, so I can't really comment. I'm curious to see what they show in CAD.
Is there any reason why Sanofi's drugs would launch to target the inactive form?
I'm sorry. Can you repeat that?
Is there any reason why Sanofi's drugs would latch onto the inactive form? It's just poor targeting on their.
The first generation, so sutimlimab and ENJAYMO, you mean why? So the question is why would they want to target it, the inactive or pro form of C1s? I think that was just a first step, going after C1s as a whole and just inhibiting all of it. They did develop an active C1s inhibitor behind that. That is their next generation approach. And that's where we saw the CIDP data. Interestingly, they're not developing their first generation C1s inhibitor in any other indication. It's approved for CAD, and as far as I know, they're not developing that any further. The active C1s inhibitor, if you look in ClinicalTrials.gov, is also being studied in CAD and also being studied in AMR or antibody-mediated rejection or transplant, although they haven't talked much about those two trials. So I'm not sure if they're going to move forward there.
I think it was just a first step that Bioverativ or True North took with targeting C1s as a complement, as a classical pathway inhibitor only, and then realized that that's a lot of drug and there's really no need to bind to the pro form. I mean, it's an inert protein, and there's not really much benefit to doing that. So that's probably where the idea for their second generation C1s inhibitor or that targets active form came from. I'm speculating, to be clear.
What are your thoughts on companies like DICE and Morphic that are actually going after small-molecule therapeutics over biologics and how that's evolving and how that would kind of influence your company in the next 4-5 years?
The question is, what do I think about companies going after oral small molecule biologics over injectables in this space? Look, I think there's always going to be a risk that you're not going to get the kind of PK levels. You're not going to get the kind of inhibition that you're looking for, that there's going to be side effects, that off-target side effects. I think it'd be great to have more options. And if there is an oral form of a complement inhibitor in the future that can show the kind of benefits the injectables, like what we're targeting, can have without any real baggage around safety or tolerability, I mean, I think it's just great. The more options, the more we can expand the market and the use of first-line biologics.
But I need to see the data first before I can get excited about that.
Do you have to screen for ANA and if you have an ANA-positive patient? Do you do anything with that or you just watch or are you still enrolled in ANA-positive patients?
Yes. The question, correct me if I'm rephrasing this wrong, is: are we screening for ANAs and are we allowing patients who are ANA-positive into our clinical programs, our phase II programs? Is that your question?
Yeah. What do you do with those?
I think, look, positive ANA patients are definitely going to be allowed into our clinical program. There's going to be other screening criteria, for example, a history of SLE that we won't allow into our program. It's almost impossible to enroll in these autoimmune conditions if you're excluding patients who are positive for ANA. So I think that's just expected. The key is that they don't have an own autoimmune disease other than the one you're studying and that they haven't had a history of SLE, for example. We had two patients in our highest dose cohort, IV, 50 mg IV, that went from ANA negative to ANA positive, but both were reviewed and had no symptoms of SLE. Both were negative for double-stranded DNA. Both were tested through an autoimmune panel and were not diagnosed with any known autoimmune disease.
Fact is, up to something like 20%, I think the literature says, of healthy people walking around will test positive for ANA at any point. I mean, it's something we have to look for, but we're not terribly concerned about it.
You keep them on the same dose going forward or you do anything?
That was a single dose of 50 milligram IV. Those patients were switched. So there were no multiple doses. There were no subsequent doses in those patients.
Thank you.
Okay.
Just another question out of curiosity. A lot of these autoimmune diseases tend to affect women differently than men. I'm curious to just know, see if you guys have done any studies on that because I think there are a couple of studies that kind of sound out of care. Women don't improve as much as men. So I'm curious what your take is on that?
Well, we're trying to get as many women as possible into the trials, men as well, obviously. Will we cut the data? Sorry, the question was women tend to suffer from autoimmune disorders more than men, and there's some evidence maybe that they respond differently to therapies than men. So are we doing anything to look at that? It was your question, right? Yeah. So as I said, we're looking for men and women into our programs. We'll see if we can get as many women as possible in there, and then we'll look at what that means in terms of efficacy. But I don't think we're doing anything in particular to increase the number of women in our trial, if that's your question. No? All right. Well, thank you very much.
Thank you.