Good morning. It's R&D Day today here out of San Diego. It's my pleasure to welcome here as well two of my colleagues, our CEO and Co-founder Jorge Santos da Silva, our CSO and Co-founder Professor Kristian Reich. And we are also joined here by two of the leading KOLs, Professor Ken Gordon and Professor Joseph Merola, who are joining us here to reflect on us with the data on the opportunity of stimulating sections. On the one hand, we will present the psoriatic arthritis 24 weeks data. So we have a whole section dedicated to psoriatic arthritis, one of our lead indications for sonelokimab. Then we have a whole section dedicated to the opportunity in hidradenitis suppurativa , a couple of important and relevant updates also on that front. And then in the third main section, we will talk a little bit about the new frontiers for sonelokimab.
Here you see the disclaimer on forward-looking statements. Please acknowledge the disclaimer. You will also have the opportunity to submit questions through the Q&A function in the webcast. Here in the room towards the end, we will have time for a couple of questions. Then please raise your hand. The presentation will also be available on LinkedIn. Please also use the Q&A function. Now, before we get started with the content, maybe I hand over to Jorge to provide a little intro for those of you that are less familiar with MoonLake, less familiar with sonelokimab. Just a very quick summary on MoonLake and on the asset sonelokimab.
Thank you, Matthias. Good morning to all of you joining us here in the room. Good morning, good afternoon, good evening to the many of you that are joining us through our webcast. Just a couple of comments here. MoonLake is a biotech company, a clinical stage biotech company that was founded in 2021 in Switzerland on the back of a license agreement with Merck. That's the German Merck that gave us access to a very exciting new technology in biologics, the Nanobody technology. But more importantly, full worldwide rights to a molecule that we're very excited about called sonelokimab. And the reason why we're excited about this is for patients with inflammation and immunology-related diseases and also addresses an MOA that we think is very important and new, and that is the IL-17A and IL-17F inhibition. And I'll come to a few more details on that.
But we believe this molecule is a true game changer when it comes to inflammation and gives us the opportunity to treat many, many patients and obviously access a very important commercial opportunity that we're going to be talking about today. Through those strong data readouts, we were able to raise significant amounts of money. By now, we've raised north of $700 million. We, as I said, are a clinical phase company. We have run three large phase IIb studies, obviously not very usual for a small company. As you know, we're having this session here directly from AAD. We will have Professor Brian Kirby presenting Late Breaker on that MIRA trial this afternoon in the conference. We also ran a large phase IIb called ARGO in psoriatic arthritis. We're very happy to share with you the 24-week data today.
We also built on a very robust large trial to give reference, to compare ourselves to standards of care. As we go into 2024, into this new phase of the company, we really have three indications that are ready for phase III. We will talk today about HS and about PsA. We expect the product to be in market in 2027. In HS and PsA Nanobodies, Nanobodies are essentially the variable region, as you see here in blue, of heavy chain-only antibodies. Here to the left of the page, you see the traditional very large monoclonal antibody. What we love about these Nanobodies is that they're very small entities, as you can see here. But we're able to bind some of these things together to create molecules that can do very interesting things.
In the case of sonelokimab, which is depicted here to the right, we have two domains. With these two epitopes, we can bind two different targets in IL-17A and IL-17F. And we even have in different epitopes, by a third domain, is all things that a monoclonal antibody cannot do. Even when we do all of these things, the molecule is 40 kD. So its administration, the maintenance dose, is a monthly dose. It's 1 mL in an injection that takes 3 seconds. So obviously, from a patient perspective, very exciting. That's the technology, which we think is very differentiating of our molecule versus any other molecule in these pathways. As I mentioned, the pathway itself is also very interesting. The role of IL-17 in inflammation is well known. The inflammation is driven by two types of cytokines, IL-17A and IL-17F.
These A's and F's form dimers, as you see there with the little balls on top on the right. And it's these three dimers that signal through different conformations of receptors of IL-17. Now, what is interesting is you have molecules that are IL-17A inhibitors. They really can only inhibit the AA homodimer, to a certain extent, can affect the signaling through the heterodimer of A and F. But only our molecule, the Nanobody sonelokimab, and another molecule called bimekizumab, a traditional large monoclonal antibody, are capable to bind these three dimers. The profile is very different. We can bind all three dimers with very similar, very high affinity. That's very different from what bimekizumab can do. So that's the technology. That's the MOA that we're pursuing. And we think that the clinical data so far is nothing less than exciting.
As you can see here, we're talking about HS, PsA, PsO, and other indications, very clear in the benefit-risk ratio. As you can see here to the right, all our clinical data suggests that we are numerically above even bimekizumab. So when it comes to HS, as you know, we ran a very large study. Professor Ken Gordon will talk about it. We'll talk about it. This was the first-ever trial to use DAPSA when it comes to PsA. Again, a large trial in this case, also placebo-controlled with Humira. Again, a disease where IL-17A and IL-17F has shown to create the best responses. And we believe that we really changed the game here, especially when it comes to composite scores and PsA. Professor Reich plays a role and where we have an opportunity to win, like we're pushing for in HS and PsA.
Today, we'll be telling you a little bit about what those other indications are that we're going to go for. Fantastic technology, very novel, a great MOA, already very, very robust clinical data. Let's dive right into psoriatic arthritis. Clearly, everyone is excited about seeing our 24 weeks data. Maybe before we get there, Professor Merola, you can provide a little bit of an introduction to psoriatic arthritis, the disease, what are the unmet needs, what are they experiencing in this disease.
Perfect. Hello all. I'm here for always the professorial role, first of all, to set the stage , talking about how we're measuring it today, a little bit how we should be measuring it. Then we'll talk a little bit about unmet need, as was mentioned, including burden of disease currently among our patients, and a little bit of a refresher on the data, where we are currently, before my colleague gets the exciting role of presenting what you're all here to hear about. I'll dive right in. These are my disclosures. I think the understanding of disease is incredibly important to our ability to treat the disease meaningfully in our patients. So just to orient you for a moment, on the left-hand side of the slide here, I'll just put this here, we have really the key domains of disease. What are they? Skin disease, psoriasis.
There's sub-bullets below that, of course. Joint disease, peripheral arthritis, you see there in a more extreme variant where you have damage. Axial or spine disease, and what's called nail disease, and dactylitis, or the so-called sausage digit. You can see there a swollen digit. That's actually one of my patients from my own clinic. And then you've seen traditional measures that seek to try to understand the activity of disease using measures typically borrowed from RA, for example, such as the ACR, to look at peripheral joints, PASI, of course, for skin, and a variety of other outcome measures to look at each of those other individual domains. Pain VAS, looking at patient pain, very important one. And then disease severity, including overarching disease severity, such as patient globals. What I want to introduce here is the MDA to begin with.
Being a multi-domain disease, the MDA is unique for two reasons. Number one, it is not just borrowed from rheumatoid arthritis, but it is a very stringent and high bar of efficacy in that it really represents minimal disease activity across multiple domains. It's a high bar. We'll talk about what those have looked like in recent studies. A lot of our systemic therapies were typically looking for 25%, 30% or so achievement of MDA at primary endpoints in general. It's 5 out of 7 of the domains. PASI 100, which I like very much. ACR 50 plus PASI 100 was introduced in some of our combination trials in the past, where we're looking at both skin and joint impact in head-to-head studies, for example, historically ixekizumab and others. It's also a high bar.
It's an important bar in that we're and so their estimates, as you can see here, 1.5 million Americans thought to be living with PsA. We typically quote, but there are variants around this, about a third of patients with psoriasis who go on to progress to develop psoriatic arthritis. You'll see slightly lower and higher numbers around that incidence. About 50% of no psoriatic arthritis, and they feel better. They feel less achy. There's a lot of psoriatic arthritis in these patients, underscored by some of the next data. So this is the PREPARE study, very frequently quoted in our literature, that PsA is often underdiagnosed and undertreated. This is just per chance. These three numbers, independent numbers, all happen to be 41%. OK, that's just by chance. We frequently quote that 41% of patients have undiagnosed psoriatic arthritis. Diagnosis of psoriatic arthritis are not on biologics.
This is nice because it's new data that was presented at this meeting, in fact. Among a survey of U.S. patients with psoriasis, 41% already fatigue has been well worked out in psoriatic arthritis. It's a key domain, as it is in rheumatoid arthritis, for example. Is bidirectional with disturbed sleep. All of that, plus functional impairment that patients are having, presenteeism, absenteeism, on metrics for work impairment. And the comorbidities we mentioned are not uncommon. A third of patients, a quarter of patients with anxiety, depression, impact on physical activity, physical function. And I think, really, it makes sense here that we need to intervene not only for patients, but for broader data, which is you ask an academic to speak. This is what happens. You have the skin responses on the y-axis, joint responses on the x-axis.
Essentially, the take-home point at very high level is patients want to be here in the red. They want to optimize their quality of life, which means getting their skin as clear as possible, getting their joints as clear as possible across all of those domains that we along with greater risk of flare, more work impairment, higher rates of comorbidities, including mental health comorbidities, worse overall quality of life. And so looking at endpoints that are composites of this, I hope I have made the case, are particularly important and relevant. I think one of our last points about unmet need is this. And this is really so obviously, a very big unmet need and at a high bar, fair, but a bar that's very, very clinically meaningful to patients. And we've hit a little bit this treatment ceiling. We've certainly hit the treatment ceiling in ACR endpoints.
I think the MDA even further underscores the treatment ceiling. That top line is really a nice summary of a complex topic, which is how do we best treat across the domains of disease. And where you see the green checkmarks, that is some of our highest efficacy by MOA in that domain. Psoriasis, axial enthesitis, dactylitis, nails, and inhibition of radiographic progression, which really means lack of erosion, lack of functional impairment over time with drugs that have a checkmark. So let's take a little bit of a data dive now, just to set the stage. And then we'll get to the exciting moment. Can we optimize IL-17 inhibition? And this comes a little bit back to the introduction that we had, the question of what is the value of IL-17A inhibition, for example, in a very objective, I would think, disease like psoriasis, for example.
Here we have plaque psoriasis data, looking at PASI 100, complete clear skin in the BE RADIANT trial, which was a head-to-head comparing bimekizumab, IL-17A/F inhibition, to secukinumab, IL-17A inhibition only. The data speaks for itself, showing improved statistically significant IL-17A/F. And this is looking at now psoriatic arthritis. This is really impactful data from bimekizumab, again, I think highlighting these points about the value of inhibiting both IL-17A/F in psoriatic arthritis. What do we see here? Our primary endpoint of ACR 50. I remind folks, if you're looking back in history, ACR 20 used to be the endpoint, primary endpoint. We've shifted to. It's more essentially bimekizumab, in this case, behaving as well as our gold standard and best to date treatment in psoriatic arthritis, which was adalimumab.
But we see a consistent message of much higher skin efficacy across other domains, much higher efficacy across other domains, including skin, as shown here with the PASI 90 data, where there's clearly improved benefit here of skin. The MDA data, and what we see here again, is now looking at a snapshot across the entirety of psoriatic arthritis domains, 45% achieving minimal disease activity. That's a fairly high bar. To be honest, broken that ceiling of MDA or ACR 20, 50, 70 in recent years. We have a couple of recent comments. So let's just refresh a little bit on sonelokimab here. So this is sonelokimab achieving high levels of response in joints. This is in the ARGO program, the Phase 2 program for psoriatic arthritis. Very standard entry criteria, very standard design for psoriatic arthritis. These are typical patients I would see in clinic.
50%, but again, as expected, pretty remarkable skin endpoint with regard to 77% PASI 90 as early as week 12. So we see skin. We see joints. Very impactful data. But this is where I want to really spend a moment. So MDA, again, I and my colleagues in the little realm of psoriatic arthritis really feel strongly about this endpoint because it is a high bar. And it's across all the domains we're sharing. And we see that 44% here, but with a slope that's increasing. And I think, really, something to keep an eye on. The ACR 50, PASI 100 data, again, this is that composite we talked about earlier. And here we see a higher threshold than what we normally see, ACR 70, PASI 100, almost a third of patients reaching completely clear skin and the highest bar from a psoriatic arthritis standpoint.
That's really quite hard to achieve, ACR 70 numbers. So it remains an unmet need across multiple domains of disease. I want to highlight that with one sentence, which is that we quite literally have a list and have had a list of patients in clinic who have cycled through multiple therapies, who are waiting for the next therapy to come along because they've tried multiple, multiple things and need to get on to another therapeutic to really get their disease under control. We talked about MDA, a high bar inhibition in psoriatic disease. With that, I will turn it over to my colleague.
Thank you. So let's turn up the heat, although I'm not so sure that this is healthy in this room.
No, the heat's quite enough.
Quite warm already. Very warm welcome also from my side. An absolute pleasure to take you through what is a new data set, too, also seeing and treating these patients for many, many years. I think it is essential to understand that you will never have a happy PsA patient if you just make the musculoskeletal disease better. There is a reason why psoriatic disease, psoriatic arthritis, is called psoriatic arthritis, because 80% of the patients have skin lesions. You have heard that there are other relevant domains. But I think we agree observations. You think nail disease is a little thing. For many of my patients, it's the main thing, because you cannot hide your hands. Everyone will look at you. It's painful. You cannot really functionally, optimally use your hand.
So even nail disease is one of those domains where you need to win if you really want to manage PsA well. I'm also excited as an immunologist. And I think one of the highlights is really to add IL-17F to the story. Look at old reviews three, four years ago. You only see IL-17A. Now there's no review that ignores IL-17F and even putting this pathway on top of other pathways like IL-1 beta or IL-20 stained in an inflamed joint. And you can just look at this. And you see, wow, there's a high abundance of IL-17F. And as we move along, we actually begin to understand what this IL-17F is driving. Just some pictures. This is what we talk about when we talk about nail disease. You will understand how relevant this is.
This is how many of our patients look like, that not only have arthritis, but that also have skin disease. The prevalence is high, as high as Crohn's disease, just to give you a feel. You analyze our data specifically with regard to the effects on multi-domains. At the same time, in the same patient, we think that we really need to elevate the standard of care. You talked about this ACR 20, 50, 70 paradigm. Let's see if we can finally develop a drug that goes beyond this existing paradigm. This is the study design. Again, our focus today on Part B. Just to remind you, what is the optimal dose in psoriasis with induction, the 60 mg with induction? We know from 17 inhibitors that sometimes half the dose that's already doing a good job in psoriasis is enough to do a good job in PsA.
So of course, we wanted to test this. And then just to understand, do we need the induction? As a scientist, probably would say yes, because patients come in with very high target levels. So you need to give a lot of drug at the beginning to bring the target. In these arms, this arm, no induction. And maybe to say this upfront, it worked. But it did not reach statistical significance at the primary endpoint. This is not a dosing scheme that we intend to therefore move forward into phase III. I will mainly focus on the 60 and the 120 with induction. MoonLake study. So we have an active reference arm. This is particularly important in PsA. Why? We're on background methotrexate. Some patients were on additional oral corticosteroids. So of course, you're going to see a response.
The later your study is, the more patients are on background drugs. So the real relevant comparison is to adalimumab. And also, and I will talk about this, if you want to do a cross-study comparisons, try to find a study that has the same reference arm and only that were crossed over to another drug or another dose. These were patients that did not even achieve a 20% improvement of tender and swollen joint counts. So a low hurdle. This is a low number of patients, hard to scientifically sound analyze. The only data that I will show you, just to give you a little feel, is this. Otherwise, this is all confusion around statistical analysis. This is the most conservative way of looking at this. Every missing data point is imputed as a non-responder. And the way we handled this.
Nice integrated view on the safety and the tolerability of your drug. We have been seeing dropout rates 10%, 15%, 20%, not with SLK. This is the third study after psoriasis, after HS, where we see dropout rates in the single-digit percentage range. I will share some safety data with you. But this is, again, a study with a very clean safety profile. And I think this is also reflected in the low dropout rate. This, by the way, also means whatever readout you do, you will get very. So this is a build. Allow me to click on this already. You see here ACR 50. You see ACR 70. Professor Merola shared with you the week 12 data. Of course, the hope, the idea was that this drug will not have hit the ceiling at week 12. It's hard to have optimal musculoskeletal outcomes.
This is exactly what you see. Between week 12 and week 24, you see a more than double ACR 70. Yes, we have a very fast onset of response. You see separation ACR 50 by week four. Clearly, a lot of separation by week eight. Takes a little bit longer, as expected, for ACR 70 to get there. But the week 24 numbers here clearly are higher than the week 12 data that we have seen. You look at the placebo crossover. I always look at placebo crossover as an internal control. And I think we can all agree the placebo crossovers very nicely validate the findings we had in Part A. The paradigm rule that you talked about, we're not even showing this year. ACR 20 was above 80% at week 24.
So we had the 60, 40, 20 paradigm, ACR 20, 50, 70 with these patients in an optimal way. Yes, we had to add comparison. But of course, we're always asked for, how does this your data compare to ADA, the gold standard, to bimekizumab, the IL-17F inhibiting antibody? So not drug. There were not other drugs could not show this coming out on top of adalimumab. The other thing you can see here is, and this is in a cross-study comparison. So we know there is always scientific limitations to this. But this is the study where bimekizumab used the same design. So this is the ADA reference arm in our study. This already at this musculoskeletal outcomes, we seem to be the gold medal drug. We knew we would have a great drug on skin. We have our phase II psoriasis results. And yes, boy, we do.
You see here 80%+ PASI 90. You see PsA. And if you, we don't show you the ADA arm here. But the delta to ADA is 20%+ for these PASI outcomes. And even if you look at bimekizumab, again, cross-study comparisons, limitations. But these numbers seem to be the gold medal numbers shown for skin manifestations in. Now, Joe talked about the relevance of making the same patient better across multiple domains. Let's measure us by our own standards. Let's really look at patients that achieve both ACR 50 and PASI 90. Let's look at patients that achieve both ACR 50 and PASI 100. And the first thing you will see is that for these high level of response, yes, indeed, you need to give the four is even bigger than some of the deltas I showed you before. Number one. Number two, forget about ADA.
It was a great drug. It was one of the great first biologics that we got in our hands to treat PsA. But really, if we now compare to adalimumab in our study, you see 20% plus delta on ACR 50 and PASI 90. An interesting phenomenon here, we had an 11% delta at week 12. And again, allow me to peek at the optimal results, where bimekizumab, the same endpoint, ACR 50 plus PASI 100, had 7% delta to ADA at week 16. But only there was no further improvement. It stayed flat. And at week 24, there was a 6%. So again, these are not formal comparisons. But you walk away with the feeling that is the best data that we have. I'll come back to this, to look at higher goals than have been shown before.
So here is something that I'm not aware that any other PsA trial has reported. This is ACR 70 plus PASI 100. So the highest level of musculoskeletal improvement and in the same patient skin clearance. And I think the numbers speak for itself. That's one out of two in my patients in my practice, I think the decision to prescribe a drug is very clear. Professor Merola talked about MDA, the multi-domain par excellence outcome. You need to not only win on all these domains, but look at the these other numbers. And if I would pick two slides to show it to you, I would pick ACR 70 plus PASI 100. And I would pick this one, because this is where the rubber hits the road. You see here the optimal data, good data for bimekizumab.
This is again indicating that especially when it comes to these high levels of response, that this is where sonelokimab scores. MoonLake has this tendency to always overwhelm you with multiple outcomes, because we think this adds to the validity and not just picking three outcomes. And they have more nail disease than psoriasis patients. So let's focus here on the middle. This is nail clearance, patients that have nail disease at baseline, but that at week 24 no longer have nail disease. And we focus here on the fingernails, because this is what matters most for patients. And ACR, is it great? And enthesitis is a very complicated clinical readout. I'm not trying to make fun here out of rheumatologists. But you know how it's done, right? You press on the point. And the patient says, ouch. Oh, one for enthesitis.
I think we need to really be better in the future to quantify this. We saw some in the more of enthesitis. In order to best look at this, we here show you patients that actually have a lot of enthesitis at baseline, so two or more. That made a lot of improvement. So when became better by two or more scales at week 24. Not sure this absolute number is telling me a lot. Yeah, it's a high number. This number is telling me something. That's the beauty of having an internal adalimumab control, because again, ADA is a good enthesitis. But sonelokimab appears to be a better really. We need to do better studies. Other outcomes. We'll talk about this, look at this in much larger studies to confirm. I promised you that I would not go into the details of these small crossover groups.
I said I would show you one. And again, take this with a grain of caution. I'm talking here about seven patients. Please, let's not overinterpret. But what you can see is that those patients that at week 12 not even had a 20 really primary non-responders to ADA. When they were switched to sonelokimab 120, we saw an MDA response that was similar to the MDA response we saw in Part A in patients exposed for 12 weeks to the drug from baseline. Again, nothing to overinterpret. But we think at least there is no evidence that non-response to ADA means that you will be a non-responder to sonelokimab, quite the opposite. And of course, we will explore this in much more to specifically look at TNF-in adequate responders. One important and this is going to be a complicated slide. And you see there will be many builds.
But one important question that you may ask is, Kristian, you showed us 60 and 120. And for many outcomes, the 60 was already great. But for some, the 120 seemed to be better. Now, why is that? And I think it's absolutely expected for a 17 inhibitor. Let's look at so-called more recalcitrant. Let's look at difficult subgroup are patients that actually have a lot of skin, that have a PASI above 10. And you see here ACR 70 on the left. You see PASI 100 on the right. Let's look at these high levels of response that are introduced. And you see that indeed, in the overall patient population, 60 is doing great. 60 and 120, very similar. But you see that in patients that have a lot of skin, you see the value of the 120 kicking in.
Example, let's look at patients that have a high inflammatory load defined by a high CRP at baseline. You begin to see a similar pattern in the overall patient population, very similar. But in those that with high CRP, more inflammation at baseline, you see the value of the 120. We analyze this data in a lot more detail. You would see a similar pattern for patients with high DAPSA. You would see a similar pattern for patients with nail disease. That this is all price surprise. We want to take forward the 60 and the 120. We hope to get both doses ultimately in the label. You start with 60. If you belong to a recalcitrant patient subgroup, if you don't achieve this optimal response, you have the chance to go to 220. Safety profile, long story short, this is the third study now.
We have exposed more than 700 patients where we in the patient population where 70% are on methotrexate, many are on corticosteroids. We were surprised that even the Candida cases are very, very low, a lot less compared to what we saw in HS. So we continue to see no IBD. There was a diarrhea, but there was a diarrhea in adalimumab, no liver signal, an injection. Sonelokimab has a large phase II study for a really good benefit risk profile. And this is more for the specialists. But it's important that you know that antibodies have struggled to, for example, get good levels in HS. And we still don't understand why do these patients metabolize antibodies more? Why is it that Cosentyx, ADA, bimekizumab, they all need to double better survive?
It's in here that again, this is the third study where our PK modeling very nicely predicted what we actually ended up seeing in our trial. What does this mean? You see here the dotted line. This is the blood level where we know our tissue concentration will be able to deliver optimal. And I'm saying optimal anti-inflammatory responses in patients that come in remain on top of or around this very high level of response. So we leave nothing on the table. Again, we feel very, we are very certain that we see the optimal doses reflected here. With all antibodies and with all Nanobodies, there's always the question, what about antidrug antibodies? And do you see ADA positive patients in red? You see patients without ADAs in blue. And you would agree with me that there is no impact whatsoever on drug levels.
Therefore, it's not surprising. You see ACR 50 response here, that there's also no impact on the clinical response. I can share with you, there's also no impact on safety. So we see a very clear path towards a meaningful phase III program in PsA. I talked about the fact that we will have one phase III in TNF-i n adequate responders. I think for most US colleagues, that's the data they want to see. We will also look at radiographic progression, which is an important outcome in patients that are to also look at markets and market size. I shared with you that PsA is as big as Crohn's disease. Conservative estimates for market size, you see numbers here around $10 billion in 2035. When we analyze this, we are so we think that a $15 billion size is still a conservative estimate for PsA.
Number two, the share that the IL-17A and F inhibitors will have within this IL-17 inhibitor class was not even addressed with this data. Again, we think this is an underestimation here. We are very convinced that the 17A and 17F inhibitors will play a much bigger role. So to summarize quickly, we are very excited, maybe a little bit tired, but very excited. I think 60% MDA. Joe, you have seen this data before. We spoke to colleagues. I think this is exciting. I will again talk about the 50% of patients, one out of two, that reach ACR 70 and PASI 100. So we want to win on these multi-domain outcomes. And I think we do. Yes, we have a fast onset of response, but probably not unexpected. We had very good data at week 12, but we feel that the week 24 data is absolutely compelling.
I talked about the 60 mg and the 120 mg. Why both doses make sense to be moved forward into phase III profile. We think we are differentiated in the outcomes that matter for patients. We think we have data that helps us to clearly structure our path forward. That means that we continue to be very excited about our rheum indications as well. Thank you very much.
Thank you, Kristian. Before we move to HS, we received a couple of questions. But maybe before we get there, Professor Merola, you've probably seen hundreds of data sets on psoriatic arthritis. You were one of the first that we shared this data with. You just heard Kristian presenting it again. Maybe you can share your reflections when you look at the data. You talked earlier about the treatment ceiling. What are your thoughts on the sonelokimab 24 weeks ARGO data?
Yeah, I'm happy to weigh in. So I can tell you, I've sat through many data presentations, as you might imagine. And we have had historically the hope that we would start to break the ceiling. Kristian already mentioned sort of the ACR 20, 50, 70 rule, 60, 40, 20, and such that were almost taught in training. I remember a recent drug, I won't call anyone out, where we were hoping for and expecting to break that ceiling again, whether it be through MDA or other outcomes. And it was disappointing. And I truly and honestly can say, I mean, the MDA data here, I agree with Kristian, is the highest we've seen, period. I mean, it's really, really very exciting. And I like the use of composites in thinking through the skin and joint endpoints for patients. So I'm quite excited about what we're seeing.
Thank you. Maybe, Kristian, one for you. One question here is, at what time point would you expect the impact on PsA outcomes to begin to plateau, given that we've seen now the increase week 12 to week 24? It still looks like it's increasing. Where's the limit?
Yeah, I don't know. I mean, the pattern that we see is the higher the outcome, the longer it takes. And that makes a lot of sense. You saw that for PASI, week 12 is great. Week 16 will probably be optimal. You saw that for ACR 70, week 24. Is this the ceiling? Are we going to see more? Could well be. I think also when I look at this combined endpoint 70, ACR 70 + PASI 100, the MDA, I'm not sure that we have hit the ceiling yet. Clearly, in phase III, Matthias, week 16 will be the primary endpoint. There is an ethical limit to the amount of time you can do placebo-controlled trial. But we will generate the data. And we will see. And I wouldn't be surprised if some of these outcomes even are seen in more patients as we move along.
Thank you. There's one more question here on the Phase 3. Anything you are planning to do in Phase 3 to minimize the risk of high placebo response as seen at week 12 on ACR 50?
Yeah, it's so interesting. You talk to rheumatologists, rheumatologists. It's a non-issue because they know that placebo is not placebo. Of course, Matthias, in a phase II, and this still is a phase II with 40 patients in each arm, we know that this whole placebo response was driven by seven patients. Six happened to be on a higher dose of methotrexate. Two were on additional oral corticosteroids. So obviously, there was a propensity in this small subgroup of placebo patients for a response.
Our phase III program will include 1,200 patients. So I think just by the size, it's very unlikely that we are going to see this kind of impact again. But it's just the fact that you cannot do these studies without concomitant meds, because that's the clinical reality. This is why I think, Matthias, the validity of this data from me stems from the ADA comparison. That is rock solid. That is the reason why we had it.
And if I may, I'll just build on that to say, being a dermatologist and a rheumatologist, with psoriasis studies, we're used to seeing minimal placebo rates, very quite low placebo rates. Placebo rates of 20s and 30s and 40s in rheumatology are standard fare in RA, PsA, et cetera. You even look at enthesitis placebo rates are 50%+ in some cases. I mean, I hadn't even noticed it until the question, frankly. But I think it's something we've become accustomed to. There's a couple of interesting commentaries on why even placebo rates have increased in PsA studies over the years, and RA studies that are pretty interesting. In no small part, background therapy, it may be a little bit even some thoughts that the disease and patient populations that are going in the studies have changed over the years.
Great. Thank you. I have a couple of other questions here. Maybe I keep them for the end so that we get to speak also about HS, which is clearly another very important indication for MoonLake for sonelokimab. You have seen the MIRA 12 weeks data, MIRA 24 weeks data. This afternoon, Professor Brian Kirby will present the late breaker at the AAD Congress at 2:00 P.M. So please join us there as well. But before we get into the details of the data set and also the regulatory feedback that we have received both from FDA and EMA and talk about the next steps, Professor Ken Gordon, maybe similar to what we've had for psoriatic arthritis, a little bit of an overview of the HS disease, the unmet needs, the challenges in treating HS. Where is the opportunity for a company like MoonLake with sonelokimab?
Well, thank you very much. I'm very pleased to be here today. I want to say that if there's any disease where there's an unmet need and desperate need for more medications out there, it's in HS. Hydradenitis suppurativa is one of the most disabling diseases. It is a disease that causes consternation in almost every dermatology office. And that's why you're seeing such a development of specialty areas of HS in academic institutions like mine, simply because people in the community don't have good weapons to treat it. And so it's being sent to specialty areas, specialty clinics, so we can try to deal at some level with these patients who are suffering horribly. So to say HS is a devastating disease is, I think, one of the great understatements of our time. Here are my conflicts of interest.
This patient that we see here in this picture, dermatologists are oftentimes accused of showing pictures just to make sure everyone else in the audience feels uncomfortable. Who's the worst of the worst when everyone's breakfast? This is a very typical patient we see with HS. Think about that for a second. You see draining tunnels. You see abscesses. You see ulceration. You see scarring. The sensation that you see in looking at this is complicated by also other sensations. This is a disease that odor is involved in. This is a disease that pain is involved in. All of those things come into play with hidradenitis suppurativa. So it is one of the most intolerable diseases that we see. It is progressive. It gets worse over time. The tissue destruction is irreversible. Thus, we need to be able to modify the disease over time.
Now, I hesitate to use the word disease modification. But the treatment of HS in the short term is, let's improve symptoms. Let's improve signs. In the end, the ultimate problem that we're trying to face is, how do we prevent this? How do we keep patients from getting there? And that's where the delay in treatment and lack of diagnosis appropriately is so critical in our patients. We talk about estimating market sizes, things of that sort. Underdiagnosis in this case, I think, in HS is rampant. But not only does it lead to changes in marketing, things like that, it has significant patient impact because it delays our ability to make a difference in helping keep these patients' lives on track and not impacted by the disease. So current underdiagnosis is a significant issue for patient care. The other issue is patient treatment.
Delayed treatment, insufficient treatment also can lead to ongoing worsening of disease. We need to have this therapeutic development that gets people to a position where they feel comfortable and they feel appropriate in treating patients, not only who have disease like we show in the picture here, but in the milder disease or in the more moderate disease that will lead to this eventually. If we can do that, we'll make a bigger difference in patient lives. It's profound effect on patients and society. Again, I want to point out that the symptoms are multiple sensory odor, depression, all the comorbid states, but pain. These patients are in pain. If you look at our patient population, the biggest reason for patients admitted to the hospital is people who are in pain, intractable pain, people who are put on opioids, which aren't particularly effective.
They say, how are we going to treat my pain? The answer that we give the patient is, we need to treat your HS to treat the pain. And if we don't have the tools to do that, we're doing that insufficiently. 30% of patients with HS are hospitalized in greater than one occasion over three years. Think about that number. That's a huge number of hospitalizations. If you can block some of those hospitalizations or shorten the hospitalizations, you're making a major impact on the health care community. Six days in hospital costing $33,000. It's a pretty typical hospitalization. Our goal is to try to change that. If you do, just shorten that by a couple of days and do an integral, do the area under the curve. Imagine the amount of money saved to the health care system by just treating these patients appropriately.
The work and employment burden, I think, is quite significant as well. There is significant time lost from work for these patients that both have absenteeism and presenteeism. I also have made the joke somewhat facetiously, but not really, that this is the one disease that I know of where the work productivity of the patient and the work productivity of the person working next to them is inhibited. The odor, the ability to put up with some of the elements that are in that milieu of that patient really can affect people around them. It affects their families. It affects people who work with them. Now, that's not proven. That's my statement in general.
But I think if you talk to people and talk to patients and say, how is this bothering you at work, which is a standard question we ask in the clinic, the patients will say, well, no one wants to be in conferences with me. It's a very significant outcome. Here's a design we put together in thinking about disease that I think is really critical for people to understand when thinking about how we go about treating it. There's a disease onset. It can happen early. It can happen late. And there is this early disease concept that's filled with nodules and then leading to abscesses. And sometimes the disease will stop there. But oftentimes, and I think more often than not, it will continue to progress. And that's when you get scarring.
That's when you get tunnel formation, these tunnels with draining, basically pus coming out of them and leading on to scarring and permanent damage. Some people have said that HS is a surgical disease. I would argue that HS is only a surgical disease when our medical therapy fails. Surgical therapy for HS is a statement of failure of treating the patient sufficiently. And if we think about surgery being failure, then I think that it demonstrates how early and how aggressively we should be treating these patients to try to prevent the other sequelae, not only to the patient, but to their family, their work colleagues, and to the health care system moving forward. The other thing I want to point about this when we look at HS studies that I think is something that's underestimated, the worsening of HS is not linear.
It's one of those things that goes up and down. It'll be waxing and waning over time, both naturally and in patients under therapy. Getting someone treated and having no flares anytime in the future to date has not been particularly successful. Hopefully, we'll change that over time. What we have to say is when we look at our tests and we look at HiSCR 50 at 12 weeks or 16 weeks or 24 weeks, we're looking at one point in time.
I think other outcomes are necessary to understand, just like Joe talked about looking at the MDA and looking at the totality of disease, looking at the frequency of flares, looking at the frequency of hospitalizations, all of those things over time, while they might not be able to be seen in a phase II or phase III trial, are things that can be very important looking at over time for the benefit of understanding the natural history of the disease. Do we have a window of opportunity? I believe so. It's an early disease or people who are just beginning to progress. How can we make them better? Remember, lifelong disease, not something we're going to be able to treat for one time point and then make it better and stop progression over time. We need better therapies. Efficacy is the key.
Getting patients better is what's going to prevent moving on to these other worsening outcomes. Shorter time to treatment, getting the diagnosis quickly. But I want to emphasize, particularly on the right, we have two treatments right now approved for HS, one more than last year at this time. So we've got 100% increase, right? Psoriasis, we have 12 biologics at this point. And we're very proud of that. But what that allows us to do with all those biologics is say, here's a patient that's treated insufficiently. We have somewhere to go. In HS at the moment, we really don't. And in HS, and we'll talk some more over the course of the day, and there's data at this meeting that really suggests that the ability to maintain patients with therapy and keep them from going into that progression over time is extremely limited.
What we need to do is not only have things number one; we need things that are effective. We need more therapies because we are going to need to use them over time to maintain patients over time. And finally, we need things that can be maintained over time. One treatment over time is better than 10 treatments over time. And I think that's really critical for us to understand. So current therapy with adalimumab and the high discontinuation rates, I think this is something that those of us who had really, really high hopes for adalimumab a number of years ago have met this problem. And it's become a very, very disabling problem for not only our patients, but for docs. This is why we see all these patients going to specialty care.
The median survival is less than a year in a lifelong drug, a lifelong disease, and a third of patients discontinue in six months. What have we really accomplished for the long-term benefit of those patients in those six months or in that year? Relatively limited amount. Clearly, we've improved symptoms. We've made people a little better for a short period of time. There is value to that. But the value is limited by not being able to control it over time. And the patient groups with the highest burden of drug discontinuation are those groups who are generally underserved. I want to point out the ones on the right and the most recent surgical patients. They're folks that we need to have better treatment. We want to prevent you that second surgery, prevent ongoing difficulties. And finally, the second to the last, the younger adults, lifelong disease.
I would actually suggest that they're some of the least aggressively treated patients because people are concerned about what happens when we treat younger patients. My argument would be, these are the patients we need to treat most aggressively that we can make the most difference for. And so here's something that I feel very, very strongly about. What do we need for an effective therapy for HS? Everything comes down to efficacy. If the drug doesn't work and doesn't work over time, you're not going to be able to block the other sequelae. Our goal is, of course, alleviation of symptoms in the short term. That patient who's hospitalized, we want to prevent the hospitalization. We want to keep the patient out of tertiary health care. We want to keep them in the office and doing well and in the clinic. And that's where we need to decrease symptoms.
But the symptoms are not only just pain. They're also odor. They're also the impact of scarring over time. Again, hospitalizations, decreasing not only hospitalizations, but emergency department visits. We don't know how many patients we get consulted on from our emergency department on a weekly basis saying, we have a patient with a bunch of cysts. Can you come in and lance them and drain them? And then we come in and say, this patient doesn't need surgical intervention. They have hidradenitis suppurativa. And they need to be put on medical therapy. And it gives us an indication that might not be clear to people who aren't in the clinical arena that there are lots of patients who come in and see us for the first time in a what we think is an inappropriate environment in the emergency department, say, you got it wrong. It happens every week.
Finally, the work and employment burden. If you're an employer and you have a patient with bad HS, you want something that works for that patient, not only because it's going to make that patient better and you want your employees to feel well, but because it's going to make a big change in the work environment. Finally, safety. Obviously, safety is critical. Risk of adverse events, we don't want to do that. It's very interesting. When we started with adalimumab and thinking about these patients who have open areas and things that we would consider to be risk for infection risk, and we started treating with high-dose adalimumab in HS patients, what we found is there's really no increased risk of infection. So even though these patients look bad, we've been very, very lucky in being able to treat patients with actually a very good safety record.
I think that as we go into drugs that have a more traditional advantage over anti-TNFs in safety in the treatment of, for example, psoriasis, psoriatic arthritis, rheumatoid arthritis, I think that safety profile that we feel comfortable with in HS will get even better. We feel very comfortable when we have a good safety record of being able to treat those patients with the earlier disease and preventing the bad outcomes in the future. Our treatment goals, obviously, are improving patients' outcomes, not only in the short term, but in the long term. Where have we gone since adalimumab was approved almost a decade ago now? In the Pioneer trials, we were able to show improvement in placebo to adalimumab. What's interesting to me is the discussion of the placebo arm we heard before in PsA. It happens in HS as well.
I have a sense that it's the volatility of the disease, that up and down, waxing and waning really does impact the outcomes of the disease. In dermatology, we've been spoiled by psoriasis over the years, right? We have 3% positive 90 placebo control rates. It's great. Kristian and Joe and I have loved that in the development of our careers. But that's not real clinical trials, right? HS is more typical of what we see. And so you'll see placebo control rates. Though they do vary quite a bit. And that's why I think we have to emphasize in looking at our clinical trials, the treatment effect, effect minus placebo, as well as making sure we look at the placebo arm and say, what's really going on in the clinical trial? Are the sites the best sites that can do these examinations?
So I think we have to be just very careful in looking at the data in the clinical trials. That's why clinical trials and doing the best clinical trial you can in HS is of such critical importance versus doing psoriasis trials where we've been spoiled. You can pretty much figure things out pretty quickly and easily. It's a little bit harder in HS. And so the quality of trials really doesn't make a difference. The second secukinumab change that we've had approved in the last year, looking at the HiSCR 50, you begin to see high placebo rates and rates that are better and improvement, but still not where we want to see. If you're seeing a treatment effect of 15%, that's not where we want to be in treating our patients. And so I think all of these factors are very clear.
Not only do we not have enough drugs, we don't have a level of efficacy that's really going to keep our patients at a significant rate and a predictable rate from having ongoing difficulties with the disease. Is IL-17A and IL-17F an improvement over IL-17A alone? I want to say there are lots of theoretical reasons. There is quite a bit of IL-17F that you'll see in IL-17F/IL-17F heterodimers, we believe, in lesions of hidradenitis suppurativa. So I think there's no question there's a theoretical benefit. But really, where do you see the data? It's in the clinical trials. And if you look at the bimekizumab trials, you do begin to see effects that are quite significant in comparison to placebo. You'll see 18%, 19%, up to 20% differences in the HiSCR 50.
When you go up to HiSCR 75, where you actually begin to see the effects of patients that really differentiate medications, you see that Q2 week of sonelokimab, 15% over placebo or 20% over placebo really begin to shine. So I believe that targeting both A and F does make quite a significant difference. I want to add something about changes in the HiSCR goal that we have. Remember that patient we saw, that picture we saw initially of the patient with HS, making that patient 50% better? It's great. There's improvement. There's improvement in pain. There's improvement in symptoms. But that's not enough for that patient. If you think about objectively having 50% of that disease, of really bad disease, what do you have? You have really bad disease.
So I think from both a clinical trials aspect and from a clinical aspect, setting our goals higher is what we should be doing. And I think that's generally accepted among the community of folks treating HS at a high level today, that we need higher goals so we can, A, get better differentiation in studies, but even more so, we can understand to get to the patient to the goal they want to be at, we need to have those numbers to tell them, this is the likelihood you're going to get there. So here's the rationale for having both IL-17A and IL-17F. You can see differences in both tunnels and in nodules. There is some thought that nodules and tunnels have slightly different physiologies and that there's a difference in potential responses of different drugs.
And so I think that is something that's very much in its infancy right now. This was published just this year. And so this is a science that's in infancy. But I want you to hold a view of this space. Looking at drugs that improve tunnels, which is not really measured very well in any of our scoring scales, IHS-4, they say, is a little bit better. But I think it's insufficient. I think looking at tunnels individually is actually what we want to do. Looking at nodules and inflammatory nodules and at abscesses, which is part of the HiSCR, they might be different. So again, this space is new. It's not something that's been developed. But it's something I think over the next three or four years, we might want to look at.
I actually think this is potentially because of the impact of IL-17F in tunnels might be a place where blockade of both A and F is of particular importance. Can antibodies improve outcomes of HS? We've seen pictures of scarring. We've seen pictures of places where you don't have ulceration oftentimes means having poor blood flow. And so does the small molecule give an advantage? We don't know 100%. There's some data from animal models that suggest that antibodies can get into smaller spaces. I don't want to say that's equivalence. But at least this gives us some sense that there is a potential advantage, especially in disease that's scarred and has irregular blood flow like HS. What about the MIRA trial? Now, I want everyone to be there at 2:00 P.M. today for Dr. Kirby's presentation. I'll actually be chairing that session.
I'll be sure to ask Dr. Kirby any question that anyone in the audience wants me to ask him. He's now very scared. I am feeling in danger on the walk over to the convention center later this afternoon. Here's the phase II, the week 12 data from the phase II trial. You can see scores and responses that are comparison to placebo higher than you'll see in other disease states and in other treatment areas. I want to particularly emphasize the HiSCR 75 numbers, which was the primary endpoint, first trial that had a primary endpoint of what I think is the most clinically meaningful endpoint we've seen so far. Looking at the 120 mg dose, you see almost a 30% difference. That's extraordinarily significant.
I also want to point out on the right, and this is something that I personally requested that we show, is to look at the pain outcomes. That's a big difference. Looking at NRS of 50, that's showing real significant differences in pain. That's what's getting people to the hospital. That's what patients complain about. That's the thing that's going to allow people to go back to work. I want to point out some ultrasound images. I love ultrasound. In looking at it, I think it looks cool. It's a very difficult process. It's something that we have to figure out how to fit into clinical research. But in the meantime, you can see tunnels shrinking with treatment with sonelokimab. Incredibly important idea. Can you get these tunnels to shrink, get less outflow? Will improve some of the elements we talked about, including things like odor.
Complete resolution at 40% is a very, very significant number. Does that mean they're gone forever? The answer is probably not in the short term. In the long term, I have no idea. I am hopeful that if you could shut these things down and keep them from draining over time, they might close. But I can't prove that. And that's something that studies with ultrasound are going to be the things that really drive us to understand over time. So what do I see in a phase III program that I think needs to be done? There are lots of new phase II and phase III programs. I have to credit MoonLake. And I will always give credit to my colleague, Dr. Reich, for many years that it's really hard to do a good phase II trial in HS.
There's a lot of incentive to get it done quickly and to get the patients enrolled as fast as possible. I think this is a disease that calls out for active competitor in trials because if you don't have that anchor, it's extraordinarily different to have understanding of what the results really mean because of that placebo arm. But endpoint selection, so the phase II trial, the MIRA phase II trial, was probably in my mind as good, if not better, than any other phase II trial we've seen in HS over time. And so I give credit where credit is due. For phase III, what I look for, endpoint selection, I think is really important. The HiSCR 75, as I said, is I think that should be the minimum what we're looking for. Getting complete clearance of draining tunnels is great. I would love to see that.
That's, again, another extremely high bar. Maintenance of response is going to be very, very important. Remember, this is a lifelong disease. People need to be able to maintain response to prevent. You can delay response for a year. But in someone's lifetime, that might not be so significant. If you can delay it, worsening for a greater long period of time, that's important. Baseline patient severity is really important in how we judge outcomes. It's been clearly shown over time that patients with more severe disease tend to be more difficult to treat in our outcome measures. So I think you have to have significant baseline disease. Optimal dosing, it's incredibly important. Obviously, a simple protocol. HS trials are hard for study sites. And so when we do them, we don't have too much fluctuation in what we do.
Patients moving around too much in those studies makes it difficult to analyze the data. Finally, sufficient number of patients, obviously, regulators like it. But with high placebo rates and patients fluctuating disease, that becomes even more important. But I think really, for me, the endpoint selection is the critical thing, getting patients to a level that's going to make a difference for them. And being able to silence a little bit of that fluctuation is incredibly important. Now I'm going to spread on to Dr. Reich.
Thank you, Ken. Yeah, Ken, thank you very much. You are here in San Diego at the AAD. We attended the HS Foundation reception yesterday. There were several hundred people in the room. The room was filled with excitement. You go to the late breakers. You see one, two, three, four studies on HS presented. Why do I stress this so much? If you look back in 10 years, this is the moment where HS became psoriasis, right? This is the starting point. This is where I think we all feel this. This is where we were in psoriasis 20 years ago. And as Ken said, this is so, so, so needed. So for us, we have really a strong interest in ultimately creating a therapy that will make HS better, right, better than with other therapies. So for us, this is great. Of course, I'm biased.
What is also great for me as a CSO of MoonLake is that I look at all those studies. I think they're still the best, right? Whatever comes out and whatever has been shown here, we think we still have better numbers. So Ken, you showed it here, 30% delta to placebo, HiSCR 75. That was the primary endpoint. You see the primary endpoint from some other studies as they were analyzed and presented. I remind you, and I'm just reflecting on the reality here, that Cosentyx, the second drug that just came in, got approved with a delta to placebo, HiSCR 50, of 11% to 12%. We had almost 40%, right, just to give you a little feel for how powerful the effects of sonelokimab in HS were. A little bit similar to PsA. And Professor Kirby will talk about this.
Of course, week 12, again, is not where the drug hits the ceiling. When you look at especially the high levels of response, and let's even go beyond HiSCR 75, you see we add another 10% here. Just going from week 12 to week 24, we have 60% HiSCR 75 here. But when you turn up the heat a little bit more, again, you need to wait a little bit longer for patients to get there. I think the numbers to memorize is 40% HiSCR 90 and 30% a solid HiSCR 100 at week 24. Now, the limitation of the HiSCR is that it does not quantify draining tunnels. And we've talked about it. We now have clear evidence the tunnel is the inflammatory powerhouse in HS. If you measure cytokines as high as in and around tunnels.
So that is the real driver of the inflammation. It's also, I think, the most burdensome phenotype of HS for patients because this is where the odor and a lot of the pain is coming from. So let's look at scores that also quantify tunnels. We can talk about IHS-4 and the usefulness of the weighting factor. But let me jump to this right to this bar here on the right side. IHS-4 100 means patients that have no nodule, no abscess, and no draining tunnel. That is IHS-4 100, right? So take away the weighting factors. It's just zero of any of the inflammatory phenotypes. We get 1 out of 4 patients to this what we call inflammatory remission at week 24. And this is not l'art pour l'art . You heard Professor Gordon saying it's the non-treated inflammation that progresses to the irreversible tissue destruction.
So this is a disease where really every percentage point more on reduction of inflammatory lesions, we think, matter when we think about the course of the disease. And we will surely continue to look into this. So just to summarize, and we talked about this HiSCR 60/40 as the new rule in PsA and 60%+ MDA. So what are the numbers to memorize here? 60% HiSCR 75, 40% HiSCR 90, 30% HiSCR 100, and 1 out of 4 patients achieving and I use this word again, inflammatory remission. Of course, these patients are not in complete remission. They still have scars and tunnels. But they are in inflammatory remission. And we explained why this is so important. I will not walk you through some patient-reported outcomes.
But the number and Eva Cullen, our Senior Director of Medical Affairs, who's in the room, she did this analysis and says, "Let's look at patients that themselves say, 'I no longer have any symptom of the disease' or only minimal." So I'm clear or almost clear. And this is 40% of the patients. So I think we begin to see numbers that we feel really will move what we can do with this devastating disease. We have clearly shown that 120 mg, the dose, interestingly, that was the best dose in psoriasis is also the best dose in HS. And we saw data, and I'm not going through the details here, where we clearly separate from other IL-17 mAbs. Also, when it comes to this long-term response, the stability of the response, we saw a crazy stability of our response in the one-year psoriasis trial.
We have all evidence to believe that we will see the stability of response in HS. This is where adalimumab struggles. It's an OK drug. The long-term control of the disease, I think this is where the drug really struggles. I already talked about the favorable safety profile. In PsA, we saw a very favorable safety profile in HS. Now, as a chief scientific officer of a small company, you know what you feel when you go to the FDA or to the EMA, right? You think you will be beaten up. You come with your phase III protocol. You have asked your 9 questions. You sit there shaking. We were all in Bethesda before Christmas.
I have to say, we were so pleased to see that both the FDA and the EMA gave us a go for all the key design elements that we asked for. We always said that we think we will get something for doing our phase II study pivotal-like. And I think the answer that we got reflects that this may really, indeed, be the case. This was a 234 well-done pivotal-like phase II. We only have to do 800 patients in phase III. You can see what other companies had to do in phase III. We will use the same protocol for these 800 patients. We will divide this likely up into two studies that we now called VELA-1, VELA-2. You know we love these star names being MoonLake. So here's another star name, VELA-1, VELA-2.
Both agencies agreed with us that we have identified the dose with the optimal benefit risk in HS. Ultimately, that's the goal of your phase II. If a company shows me they still do two, three doses in phase III, I would be critical and say, "You haven't done your phase II homework." We have one dose here. That's the 120 mg with induction. Will be a straight shoot out versus placebo. Placebo patients cross over. We treat for one year. Then there is a chance for patients to continue in a two-year open label extension. I have been doing clinical trials all my life. This is the simplest phase III you can think of. I think this is great for patients. This is great for physicians. Of course, our primary endpoint will be HiSCR 75, right? I will come back to this.
But we will move it to week 16 to give the drug a little bit more time to really work. One little element here, we have seen companies recently struggle to see safety events popping up in their study that might or might not be the intrinsic comorbidity of the disease that you treat. And of course, if you want to protect yourself against seeing some numerical imbalances, your placebo arm has to have a healthy size. So we will not do some 4:1 or 5:1 randomization. We will do 2:1, right, to make it attractive for patients but to avoid this risk that suddenly you see a rare event overrepresented in your small placebo. And then you have a problem explaining what is really going on. So again, we are here at the AAD.
We get a lot of, I think, extremely positive feedback from sites that are interested. We are really happy that we can now start VELA-1 and VELA-2. We think that this drug really deserves to be developed and brought to the patients as quickly as possible. Allow me to come back to this pivotal-like design for one other important question that we always get. This question is, "Yeah, your phase II is good. But you will be compressed in phase III. Everybody is compressed in HS going from phase II to phase III." We do not think so. You will be compressed if your phase II is a single center, non-controlled PoC study where you do crazy things that you would never do in a pivotal-like trial. I'm using some rhetorical language here. This is the other thing that we get from our pivotal-like phase II.
We get a protection against being compressed going from phase II to phase III because our phase III study will be a replication of our phase II. You see here all the important study design elements in our phase II. Everything that's green means we will have the same study design element in phase III. So basically, we change very, very little. We move from phase II from week 12 to week 16. We do some other mild adaptations in the statistical readout. But basically, our phase III is our phase II. So we don't see any reason why we should have a high risk of being compressed. And just to point this out, even bimekizumab, their phase II was a PoC study. They even used a loading dose that they never used in phase III. And they did not identify their best dose in phase II.
So they had to take several dosing into phase III. This is all very different, right? This is not something that we think we are going to face. So we are very enthusiastic about the great feedback. We continue to be excited about the data. And we think we have a very high chance to replicate this great data in phase III.
Great. So let me take over here for a few minutes to talk about another big question that always gets asked around HS. Is HS big enough? Can you really build a business on HS? Can somebody build a franchise on HS? And we set out to find a strong fact base to make this conversation fact-based and not just idea or opinion-based. You've seen this picture from our side before. This has been our early estimations of what the market could be. We felt that there was a number missing out there on what can this market really become. You know that our perspective is that the market is about $2 billion in sales right now. And we will prove it with you with facts that this is the case. But we also know that this market is mostly driven today by Humira. You heard from Professor Gordon.
You heard from many other people. This is probably a misleading number of market size because there is so much limited durability. So few patients benefit from adalimumab to start with. And then the majority of them drop off within a year. So all the sales that you see here are dynamic sales. They're sales that created new every year. It's probably not a good indication of the market size. And we believe, based on some estimations that, again, we will detail further today, that this market can really go in the United States well above the $10 billion mark. One of the critical drivers to start with is, of course, that we will see what we saw in psoriasis back in the day, what we now start to see in AD and in many other indications, that you finally start to have different therapeutic alternatives.
So these poor guys can sit in their practice and have a solution to present to patients. You have Cosentyx just recently approved. We're eagerly awaiting the first signs of commercial performance. You know that in 2025, bimekizumab is expected to launch in HS. This brings the IL-17A/F MOA with a traditional monoclonal antibody that Ken already mentioned. In 2027, we come into the market with the results that you've already seen of the MIRA trial that, again, you will see today detailed in the afternoon in the Late Breaker. We come in 2027. And obviously, there's other products that are coming in, like the JAK inhibitors.
Obviously, these are more late-line therapies. And obviously, the relevant element here and you saw the numbers is that we're really bringing the best of both worlds with this unique MOA, which is IL-17A/F, but also the characteristics of sonelokimab as a particular molecule. And so you see this leading HiSCR 75 response. 75 is great. We even want to go higher than that, the effect on tunnels, which is very unique to our molecule, a very interesting drug to potentially use in the clinic because of the speed and depth of response and how you can disease control over time, plus all the other excellent profile elements that we've started to build with SLK.
So a market that is growing also because there are several options and obviously an option here that really seems to be stepping over the shoulders of others. So to factualize some of that and I don't know if factualize is a real word. But well, let's assume it is. OK, thank you. We went and said, "OK, let's look at the real world.
Let's look at the real facts out there." What we did to do so is we used claims in the United States, so unique U.S. patient claims. We have a very large database that covers about seven to eight years of longitudinal data. So it's very significant and covers about 75% of American lives, so quite a good coverage. And we immediately use a very, very stringent filter, right, in this big pool of patients. Let's find the patients that are bona fide HS patients, patients that have received an HS code and have been treated for that disease. What do we find? We find an absolutely staggering number. If we look at claims today, cumulative from the last few years, there are 2 million Americans that are diagnosed and treated for HS, right? So this doesn't even include the people that are diagnosed and not treated.
This does not include the people that are undiagnosed, which I think, Ken, you would agree is probably the large majority. But bona fide patients today, 2 million Americans. I remind you that this is a chronic disease. There is, unfortunately, no cure. So if you were a patient in 2016, believe me, you're also a patient in 2024. So this number alone would make it a very large market by any means. It's also something that, despite all the challenges, people are recognizing more and more. We have a very healthy rate of increase of the number of diagnosis of about 200,000-250,000 patients a year. It confirms that there's a lot of potential out there and that we can bring a lot more of these patients into the clinic. If you look at biologics, of course, the picture is very disappointing.
So we have 40,000 patients being treated with adalimumab , for example, in 2023. The total number of patients that is treated with biologics is a little bit higher, about 30% of about 60,000 patients are treated with other biologics, which, again, tells you there's probably unmet need that these patients are bumping around and not getting the treatments that medically avoid all the dramatic long-term consequences that Professor Gordon has talked about. And last but not least, we do see that the biologics are getting some uptake. They are being more and more used as all these patients come into the market and get diagnosed. But obviously, this is starting, as you can immediately calculate, from 60,000 over 2 million patients. This comes from an extremely low base. I want to deep dive on a couple of these numbers to really drive some points home.
What you see here is 2 million patients diagnosed today. So they are in the claims. We know that they're there. They're being treated in some health care setting. If we simply would assume that the market behaves as it has in the last eight years, just the historical diagnosis progression, we would get to about 3 million patients by the time we plan to launch. If you continue what we consider as a very conservative assumption of just continuing to diagnose these patients, we believe that we get to about 5 million Americans when we come to peak sales. What this also means is that we have always this discussion: what's the real prevalence of this disease in the real world? Wild numbers out there. I think in the last years, you see that and Professor Gordon talked about it.
We're sort of netting out at this 2% of prevalence. This is, again, an estimate. We can already show you that we find 1%. 1% is already in our claims, right? So it's very likely and these are just the diagnosed and treated. It's not a big stretch of the mind to imagine that, indeed, the real prevalence is 2%, maybe even a little bit bigger. Certainly, there's already a base here to create a very large therapeutic area. Putting some numbers to the drama that Professor Gordon talked about and, again, this tells you about the huge opportunity there is for biologics. Here, what we do is we take patients in a given year. We see what happened to them as they go into years two and three. The picture is horrible, right? Majority of patients get treated with antibiotics, steroids, opioids, et cetera.
This is the same in year one. Things don't really improve to year two. A lot of patients, about a third of the patients here, our numbers match. So that's good. About a third of the patients end up in the ER for one or multiple visits in the first year. Things don't improve as time goes by. A significant percentage of patients get surgery. Things don't get any better over time. And obviously, you see that there's about 3% of patients that are being treated with biologics. And that number dramatically decreased in year two or three. And then, of course, if you look at the Sankey diagrams and you follow all these individual patients, it's a very sad story of patients just moving around from therapies, from sites of care all over the place but without a real solution.
So lots of patients that really need a medical treatment that delivers on all the dimensions we talked before. Other IL-17A is not it. I think we've heard this from Professor Gordon. I think we also see this in the claims in the real world. Here on the left, we show you Pioneer data, right? So this is the famous picture from Pioneer that took all the patients that responded at week 12, the primary endpoints. I remind you that 50% of patients responded. And then you track those patients over time. And you see that even those patients that responded very quickly lose response to the drug to a point where the placebo actually performs exactly like the drug, so really not something that provides a durable treatment and obviously has other limitations in terms of efficacy.
If you actually look at the claims data, if you actually look at the claims data, you see the story in numbers that we've been talking about. The median time that patients stay on adalimumab is 11 months. So obviously, this is not going to be a solution for a chronic disease like this one. And oftentimes, we say, well, this is probably a U.S. problem. Access is complicated. Probably not because if we look at data from different registries in Europe, you see exactly the same picture, right? So lots of patients, lots of need. Clearly, adalimumab is not a solution. But it also starts telling you the story that patients cycle every year on adalimumab . So again, this story that the market size probably requires a little bit more analysis.
This shows you the progression of the biological therapy over time in all the patients until 2023. We still have full data for 2023. But it already tells you a good picture. As I said, 3% of patients being treated. This is dramatically lower than anything else that you see in immunology, in dermatology, in rheumatology. We probably should be seeing about 15% or more. Of course, for the physicians here, 15% penetration is still a disgrace, still a disgrace. But clearly, 3% is we need to get to 15. And then we worry about the next step. But obviously, a lot of potential, a lot of potential, a lot of potential here. What we're showing you here is, again, a double click on these biological sales so that you understand what we mean by dynamic market. Here's the 2023 data that is available.
You see the number of patients that are treated. You already see that it's not just Humira. There's a lot of other biologics that are being used and on which patients jump back and forth. Considering the fill rates that are available, the net price that we know of, you see that about $1.6 billion of these sales in 2023 belong to Humira. The total is about $2 billion. But what you can already see is, of course, you have about $500 million sales here in other biologics that are being used. So obviously, a lot of use. But you also see that, of course, because the patients fall off Humira towards the end of the year, these are new sales every year. So please do not look at the Humira sales as a proxy for the size of the market. It is incorrect.
One of the other things that I think are very important, what will happen now that, as Professor Gordon mentioned, we have all these new drugs coming in? Maybe the next one takes the market. That's it. Nobody else can do much. I don't think that's the story that you see in dermatology. Here, we're bringing you back the psoriasis example, this complicated chart. But I will use it to illustrate a couple of points. You see here in the dark blue, that's Humira launched in 2005, had a very slow uptake. But as you see, took a big market position up to about a third of the market as the market grew. Then in 2015, you have Cosentyx being launched. That's the lighter blue. You see that it also built its position and grew the market to about 15% of the market.
Then in 2019, you have the incoming IL-23s, which obviously are great skin drugs. And you see them creating their own market. So I think this tells you a story of there are a lot of patients here. There is a lot of potential. And if you continue introducing MOAs and therapeutic solutions that really create a delta, there is ample opportunity to take market share and to continue growing the market, especially a market that we know is so depressed like HS. So this concept of like, well, you only come in 2027. There's no way you can make sales, that would be true if the drug was not a very, very good drug. So this is another important point that, for us, is important to outline.
So we stick with our idea that just based on the prevalence that we see, just based on very humble biological adoption in the next whatever, 12 years, 11 years, we really can get to $10 billion relatively easy. Probably, the market is much bigger than that if you really consider that we are not even seeing underdiagnosed patients or nondiagnosed patients in these claims and considering that if we get to any biological penetration that is anywhere similar to any other of these indications, we get to a market that is extremely sizable, right? So if anything, we believe that we're being somewhat humble in our predictions for the market. But now, there is clear evidence. We can find every patient in the United States. You know what the dynamics of the market are. And you really see the potential for molecules like Cos and others.
I want to just highlight a few other elements that I think are relevant from a market perspective. Oftentimes, we are asked, well, but could MoonLake do this? Could MoonLake go out there and commercialize it? It's interesting. It's a very particular distribution of patients when you look at HS. You see here the hotspots. They tend to be in large urban sites. There's a number of reasons for that. What happens in the West is a bit different from what happens in the East. But in general, these patients are very concentrated. So it's not one of these diseases like psoriasis in which you have to cover the whole market, if you will. But whereas you can see also here in the left, it's a very steep curve in terms of the health care organizations that are seeing half of the patients or 70% of the patients.
So whether it's us, whether it's anybody else trying to push into HS and we know that there's a couple of companies now pushing hard here, this is going to be a very particular market when it comes to targeting, very different from some of the other dermatology indications. Another element from news from the market that I think is important, I think you've seen this, the penetration of bimekizumab, Bimzelx in psoriasis as the first entry market for an IL-17A/F drug has been incredible. I think a lot of people were surprised. We weren't. We knew that the market was desperate and very interested in using IL-17A/F because of the clinical data that you have in psoriasis.
But this really illustrates the point once again that if you bring a proper drug that really changes therapy, that provides new opportunities, the market will take it, even in a competitive place like psoriasis. And obviously, if you try to create a parallel to sonelokimab, it's very obvious that versus bimekizumab, versus any of the other competitors, we are sitting on a data set that is extremely strong that probably will allow us to clearly differentiate when we come to the market, both in HS and in PsA. So I think this bodes very well in terms of how we will be perceived by the dermatologists, by the rheumatologists when we come for HS and PsA. So just as a quick summary of this particular section of the market, sizable underdiagnosed market. I will continue insisting on this number.
There are 2 million patients that are diagnosed in this country. This market is very, very large and needs to be addressed for all the reasons we heard. The biologics are there. They're growing. But there's a lot to be done. There's a lot of value that we can add by adding MOAs and therapeutic solutions that solve the problems that Professor Gordon mentioned but also in PsA that Professor Merola mentioned. You see that these patients are cycling all over the place. We need to balance and stabilize and control the disease with drugs that act strongly over time. And obviously, this will lead to very interesting conversations also with payers, et cetera because obviously, there's a big patient burden and a big health system burden, a big societal burden that we can manage here if we can control these patients.
As I mentioned, I think when it comes to sonelokimab, we really have a true opportunity to lead. We work for much longer than other IL-17A/F mAbs do. As Kristian mentioned, even on a primary endpoint like HiSCR 50, we deliver a lot more response than current options. And when it comes to bimekizumab, our IL-17A/F monoclonal competitor, I think you see that no matter how many scores you look at, we're always consistently above that drug. So this is a very, very large market. And I think we're well positioned to be the leaders. And I hope this starts to bring some facts to the table. And it's inescapable that this is a very large market. I hope this starts to help with that conversation. Maybe I stop here. Matthias?
Yeah. Thank you, Jorge. Maybe in the interest of time, one question that we can take here. We received one specifically for you, Professor Gordon. The MoonLake team seems very confident of being able to replicate the MIRA results, the phase II results, in their phase III program. Do you think that the results will be replicated? Or is there a reason to believe that the data would compress in phase III? So it's a great question. Do you want the crystal ball? Well, but that's really it. So when you look at that question, what are you thinking about?
You're thinking about what's the likelihood of having reproduction versus compression of the results? I'm not sure I'm familiar with the results that aren't quite as good in phase III. I think when you look at the phase II to phase III transition in development of many drugs, as I think Kristian pointed out, there are changes in the protocols. There are changes in how you go about the trial, the different entry criteria, things of that sort. The way to try to best protect against that is to have your phase II trial be as similar to a phase III trial as you possibly can. And so when I gave credit to MoonLake for doing a phase III like phase II, there's a reason for that because the likelihood of it being predictable goes up. Is it 100%?
No. But I think if you think in a normal trial that maybe it's two-thirds predictable, you might go up to 90% predictable. Those are numbers completely I picked out of the thin air, right? But what you're doing is protecting against that by having your phase II be as good a trial as possible. Obviously, in phase III, selection of sites, other things going on in the world that can change enrollment, all of that can change the outcomes in phase II to phase III. But I think that if you look at the MIRA trial, it's done the best job you possibly can to protect against compression that we've seen in HS. Is it perfect? I hope so. I would love to see it. I mean, we've even seen some trials, programs get better in phase III, right? It happens.
And it's happened in psoriasis a number of times. We are very hopeful, at least I am hopeful from a personal standpoint, that it will get better, not because I have any vested interest in it but because I want my patients to have good outcomes. And so I think that you can never guarantee anything. But MoonLake has set itself up for as much success as you can possibly get. And I think that's what your goal is. So I'm feeling pretty good about it. But I would never go up and say, "I guarantee it by any stretch." Well, I know there wouldn't be.
Yeah. Not quite the guarantee. But thank you for the answer. I think in the interest of time, we'll park other HS questions for the very end and maybe speak a little briefly about the next frontier for MoonLake, for sonelokimab. We've seen the PsA data. We've seen the HS data. We've seen the positive regulatory feedback. Jorge, what's next for sonelokimab?
Yes. So let's look at the new indication. I think we're good on time here. Obviously, we're going to our last significant update of today's R&D day, which are the new indications. As you know, we've been focusing quite a lot in all our communications, certainly today on HS as our main indication in dermatology and PsA as our main indication in rheumatology. But obviously, we're always very excited about our MOA, not only because we're only one of two molecules that can actually do this type of inhibition with all the great characteristics that we've already talked about of it being an antibody but also because in our minds, the pathway, the IL-17A and IL-17F pathway, is something that is a little bit of a crux in a lot of signaling that happens in many of the inflammatory diseases.
So you see there's a lot of upstream pathways that signal through IL-17A and IL-17F. And many of them have been tried. And some failed in a lot of these indications. IL-23 failed in HS. C5 failed in HS. There's several of these that failed. We believe that if you go too much upstream, there's too much redundancy that can be compensated. And we believe the same happens when you go too much downstream, IL-36, et cetera, being a great example. So being a crux, we believe that there's, of course, a lot more potential to capture this pretty fundamental, basic element of signaling to harness the inhibition to address many other diseases. Many of you are familiar with this picture. As always, we try to put as much information as we can in one single piece of paper.
But you remember this story. You see here a little bit the various indications that we see immediately as potential because there is information that IL-17 is involved, that IL-17A and F is involved, that the inflammation is sitting very deep in tissues where our Nanobody can reach. We've listed this out before. We divide them into different groups. We have this thing that we call the MoonLake core indications. These are where the evidence is the strongest, where we ourselves already have some evidence that, indeed, we can become a winning therapeutic solution. In blue, of course, you see the indications that we already have very large phase II data for. There's a few others that we haven't pursued yet. And then, of course, there's horizons with other indications. And there's a lot of ideas and options in dermatology. There's a lot of ideas in rheumatology.
There's also a lot of other opportunities in many other tissues. And the opportunity from a market perspective is very, very large. Now, for a company like ours, we have to choose very wisely, right? We are not a very large pharma company that can throw money at 20 trials at the same time and see what happens. We have to be very judicious as to how we use our cash position and our knowledge to really make a difference in additional indications. So that's really what we took into consideration when we thought, "What are we going to be doing next?" We considered, "OK, there is the HS phase III. There is the PsA phase III. These will all read out in 2025 and 2026," as we already mentioned publicly.
This is, of course, a big effort for a company like MoonLake to scale up and go after these indications. So what are the strengths that we can build on to choose the next indications for us? So one critical criteria is, "Let's build where we already have leadership." So let's really double down on dermatology and double down on rheumatology because, obviously, we have the sites. We have the connections with the scientific and the clinical network out there. We also have built our own organization with people that know a lot about dermatology and rheumatology. So it makes sense to go after these TAs rather than completely new ones. Again, let's look at particular diseases in particular sites of inflammation where our Nanobody can really make a difference.
And in what I would proudly call MoonLake style, let's go for indications with designs where we can make a difference, where we can make an innovation, where we can change something, be it the composite scores in PsA, be it the HiSCR 75 and the inflammatory remission in HS. Let's try to make it different rather than the me too stuff, as Kristian mentioned. So there are four programs that we will be initiating in short order, two of them in dermatology. Don't worry. I'll go through a couple a little bit more detail. We will introduce a completely new indication to our program, palmoplantar pustulosis. Again, I'll share a little bit more detail.
But this, for us, is one of the next HSs, no drugs approved, horrendous disease, huge disease burden, and unmet need. We're going to start a project and a trial on PPP, as we call it. In derm, we will strengthen HS. We will do so by running a clinical trial in parallel with our adult trial in adolescent HS. I remind you that no drug has created data, clinical data, in juvenile HS patients. As we heard, this is probably the time where we really need to start treating the disease to avoid all the problems that happen after that. Of course, as you can imagine, this will reinforce our position as the partner in HS when it comes to dermatology. On the rheum side, a little bit the same play. We will introduce a new indication.
That's axial spondyloarthritis. So that continues to build our position in the seronegative spondyloarthritis, which, of course, includes PsA and now AxSpA. We will do radiographic and non-radiographic. We will add another supportive phase II in PsA to bring imaging to match with clinical outcomes. I'll go through that detail. Again, this is to strengthen our presence in the current indication so that we can lead PsA together with rheumatologists. That's a little bit the picture. Allow me a couple of minutes to go through some of the thinking and some of the details that are associated with these indications. As I mentioned, PPP, I will no longer say palmoplantar pustulosis. Let's just go PPP. It reduces time.
As I said, is also a priority for derms. It's one of those diseases where you're sitting there in the office going like, "What do I do?" Huge unmet needs, very high prevalence. So we think something that, of course, others have already shown, bimekizumab as a case series, showing that IL-17A and F is really probably the first MOA that can really make a change for these patients and always giving a little wink to the psoriasis side. Of course, a lot of these patients have of psoriasis patients have palmoplantar involvement. This is another opportunity for us to stay close to the psoriasis patients as we are with PsA. As I said, strong clinical evidence that IL-17 will probably make a huge difference here.
For PPP, I just want to mention a few things. Again, I want to insist on the fact that no approved therapy. The usual people that have failed have already failed. So this is something where there's a big need. And it's really a chronic inflammation. I want you to remember that these patients, which is about 0.3% prevalence, really lead very difficult lives. It's the palms of the hands, the bottoms of your feet. You cannot walk. You cannot grab anything. It's painful. As you can see from the pictures, this is not something that you want to suffer from, obviously. As we build our phase III, you will see as we announce the details that we are introducing again higher and, I think, quite ambitious outcomes in terms of what we're going to be reading in this phase II.
We believe the design that we have will allow us then to move into phase III in a disease that, again, has zero options. Juvenile HS, as I mentioned, typically, drugs are approved in HS. And then, of course, you have peds and PIP. And you have to do some work in adolescents. But everybody just postpones this to observational studies in the market. You see the effect that we have on tunnels. You see the needs. Professor Gordon talked about it, to treat these diseases early so that you avoid these irreversible lesions. We are so good in the tunnels. We thought, "Let's turn the argument around. Let's not wait for the market to address these patients. Let's commit to a trial where we really have the opportunity to control the irreversible damage and provide a solution to end the disease as its actual onset."
This will run in parallel with our adult trial. The idea is that we will have both results by the time we get to market and, again, be a true partner in HS but also the first company that has clinical data in adolescents. A couple of very interesting elements about our youth programs. Obviously, suffice to say that on the juvenile HS, we'll continue having the primary endpoint very high, HiSCR 75, et cetera, et cetera. In AxSpA, as I mentioned, both radiographic and non-radiographic, as you know, there are some limitations that you also see in PsA with the current standards of care. Together with PsA, this allows us to continue trying to lead in seronegative spondyloarthritis, which is obviously a market basically the size of RA.
And we already know and here, again, we're following the coattails of others. We already know from some of the bimekizumab cases that AxSpA works. And obviously, you're talking about very deep tissues, very difficult-to-reach tissues. So we believe that our drug will have a key advantage here. I think you're all familiar with AxSpA. Again, very large disease. I mean, the prevalence is extremely high. What I would really like to call your attention to is the innovative design that we're going to be running here. So we're going to be measuring all your traditional clinical outcomes, what I would call subjective outcomes like ASAS, et cetera.
But we will be complementing these rheumatology trials with an innovative imaging set where we do MRI and PET so that we can really go into the tissue and see exactly which joints, by how much, is our drug able to impact in terms of inflammation. So not, as Kristian would say, the press and say, "Ouch," but the press and say, "Ouch." And then I actually look into your joint and say, "Here's where sonelokimab is maybe making a difference or not," right? And we believe that this is the first time that this type of imaging technology is used together with clinical outcomes in a phase II setting. And as you can already see, this is a way for us to start creating data that nobody else has.
So rather than competing just on ASAS 40, me versus you, it's that plus the showing that in the real tissue, we can make a difference. In PsA, it's going to follow the same logic. This is a supporting phase II to our phase III program. Again, here, it's about doubling down on these indications. And it's using this innovative imaging. It's, again, MRI with a slightly different modified PET strategy that will, again, allow us to confirm the clinical measures that we show in phase II for PsA but bring in the imaging to show that we're really acting deep in the tissue and really resolving the inflammation on particular joints, be it in the fingers, be it in any other joints.
So again, us innovating here to bring the subjective clinical outcomes together with objective measures, which we think will contribute greatly. And I hope you agree, Joe, that this will hopefully help in getting a bit more precise when we're treating these patients in the real world. You will see this in the document that is now already available at our web page, the document you're seeing. This is a bit of a summary. We're talking about all diseases with very high prevalence. We're talking about very high markets. And we're talking about largely empty spaces, especially when it comes to some of the new indications that we're following. So we're very excited to add that to the mix. Again, I'm not going to go through the detail here. This will be available for your careful perusal.
We believe we'll bring about 200, maybe a bit more, patients into these new indications. As you can see, the time that it takes for us to get to the primary endpoint of HS next year and to PsA primary endpoint end of next year, beginning of 2026, you will start seeing news from all these trials as we go through 2024 and 2025. Obviously, what we're trying to achieve here is increase the value that we are capturing with sonelokimab as a drug. We've told you before that we believe that we have about $5 billion in sales or so that we predict with HS and PsA. But we believe that adding these additional indications in derm and rheum will allow us to continue building on the value of this asset so that we really make it the very large asset that we believe that it is.
This also starts to build the picture of what we're doing from an R&D perspective at MoonLake. We now have bona fide, let me call it, BLA-enabling programs, the phase III in HS, the phase III in PsA, and now phase III in juvenile HS. We're filling the pipeline with what comes next. So we have the phase III-enabling studies, as we call them, PPP, AxSpA, and the new supporting PsA study. And we never really have time to go into this. But obviously, rest assured that we do a lot of work in terms of biomarkers. We do a lot of work in penetration. And we do a lot of work in testing in human models potentials to expand the use of sonelokimab. But this really enriches the program and the set of catalysts that we have over the next years. Maybe I stop there, Matthias.
Thank you, Jorge. Maybe briefly, a couple of minutes now in the last section, some strategic considerations and a brief update also on the financials of MoonLake before we then open up for Q&A. So maybe to summarize, what do we believe do we have with sonelokimab? I think, on the one hand, a very, very promising, I would say, leading MOA. We have seen the data from bimekizumab. We've seen our data now in multiple indications where we would argue this is really the leading MOA. This is a differentiated MOA that has shown the highest efficacy outcomes across multiple indications, but not only the highest outcomes but also durable outcomes. Just yesterday, we saw a presentation on IL-17A/F inhibition with four-year data, which was, I have to say, very, very impressive to see the durability, something that we've seen it now for the TNF inhibitors in HS.
You don't see this with other MOAs. So really high efficacy, durable efficacy, but then also very favorable safety profiles. IL-17s are a very safe MOA. And I think from all the over 700 patients that we have now exposed to sonelokimab, we don't see any difference. We don't see any signals that would be worrisome. We don't see any cancer, any cardiovascular events, any deaths. We don't see any signal for SIB. We don't see any signal for any liver problems. So really a favorable safety profile that we observe with sonelokimab. And then ultimately, I mean, there's only two assets that share this MOA. There's bimekizumab, the traditional antibody. And then there is sonelokimab, the innovative Nanobody that also binds to albumin, further helping the tissue penetration, getting the drug to the sites of inflammation.
But even beyond this MOA, we do believe we have a differentiated molecule in the MOA. We've shown you the data, the efficacy data. Not only do we aim for higher outcomes, we use HiSCR 75 as a primary endpoint. We look at IHS-4 100, full clearance. We look at these very high like ACR 70, PASI 100 that no one has ever shown before. And we get to outcomes that we have not seen in any other clinical studies before. So clearly elevated performance that we bring to the table, higher goals. We talked about it, higher primary endpoints than that other companies are going for. And then ultimately, also, we didn't speak about it now, but a very convenient posology. Sonelokimab is in maintenance, one injection, 1 mL once a month with an autoinjector. Takes a couple of seconds.
So a very convenient posology that also we believe will further help us differentiate in the market versus other treatments. Now, how do we take it forward? And I think this page is a page that many of you have seen. Some people say, "Well, the MoonLake guys, why did they show it?" But we don't mince words. We see it still continuing. There's two possible paths for MoonLake. There's one, the current owner scenario. There's the other one, the better owner scenario. We could not be in a better position than that we are in right now. We have very, very strong clinical data from the ARGO study, from the MIRA study. We have very supportive feedback from the regulators, from the FDA, from the EMA. Clear path ahead to we know exactly what we need to do. We do have the team. And we do have the money.
So we couldn't be in a better spot to drive this forward. And this is what we're doing. On the other hand, nothing has changed on this one. It's also no secret that I&I is in a very attractive space for pharma companies. They're looking for assets. And there's not a lot of assets like sonelokimab that are as de-risked as sonelokimab is and that it addresses multiple billion dollars across very large indications. So no real change here. The strategic path forward remains really unchanged. Now, a brief update on the finances. Here you see that was, I think, filed yesterday, a week ago, in our 10-K. You see it there. We're in a very, very strong financial position. At the end of the third quarter, we had close to $500 million on the balance sheet. We continue to operate in a very focused way.
We're a single-asset company focused on the development of sonelokimab. So in the fourth quarter, a cash burn of approximately $16 million, which includes actually half of that as prepayments for the manufacturing runs for 2025, now getting ready for the commercial supply with the launch expected in 2027. We've also utilized in the fourth quarter and then the beginning of the first quarter a little bit the at-the-market facility that we have to top up the balance sheet, to really drive forward and double down on the development of sonelokimab. Jorge presented the additional four programs that we're running now.
But now we're in a very, very strong financial position with funds that are able or allow us to run the full phase III program in HS, the full phase III program in psoriatic arthritis, to do the additional indication work that Jorge presented, submit for regulatory approval, and also covering all the other baseline, really runway until the end of 2026, well beyond the next clinical reach, so putting us into a very, very strong financial position to drive forward the development of sonelokimab. This is the last page that I want to leave you with. It's like, where do we see now sonelokimab fitting in the world of I&I? And if we look at I&I indications, we see broadly three types of inflammation. Type I or type II is the one where you see dupilumab, where you see the atopic dermatitis, allergic asthma.
This is where dupilumab is currently the market leader. Then you see the other type I inflammation. This is one where people talk about the IL-1 alphas. We believe, for us, this is really the type III inflammation where you have HS, where you have PsA, where you have PPP, where you have a lot of other indications. That's where we believe IL-17A and IL-17F is the leading MOA. And if you can then deliver it with a Nanobody like sonelokimab, you are in a very strong position to really unlock the potential in many, many large indications in I&I. With that, opening it up for Q&A, I do have quite a few questions here online. But maybe starting in the room whether there's any immediate questions? Yep.
Yeah. Patrick Trucchio and Steve Ball. In HS, can you guys just talk about in a scenario where one of the phase IIIs misses on efficacy, can sonelokimab still get approval with a successful phase III plus the MIRA trial, assuming that the other phase III that failed doesn't have any safety signals or anything?
Yeah. Maybe I repeat the question. And then, Kristian, you want to address it. The question asked here from the audience is, what if one of our phase III studies in HS fails? If we fail to meet the primary endpoint, would we still have a chance to get approval?
Yeah. I mean, I don't know what the primary endpoint the FDA and the EMA ultimately say. But you have seen, for example, in Cosentyx that not in all studies, all arms met the primary endpoint, right? Is Cosentyx approved? It is. So I think, in the end, it will be down to the real data. I have to say, why I struggle to answer this in this way, I need 50 patients to show statistical significance to placebo, right? I mean, the size of the study is completely driven by safety. So if you ask me, is there a real risk that we are not going to show statistical superiority to placebo in HiSCR 75 in one of the studies, you should never say no. But the risk is very, very, very, very low. So we would need to see, how far are we away?
Is it still better, but just not reaching statistical significance? Does the safety look good? Clearly, the 234 patients that we have in phase II will be integrated part of what we submit, what regulatory authorities look at. So we are very confident that this phase III has a good chance to come out positive.
Thanks. Rami?
I guess, really quick, do you guys see a difference in efficacy between biologic naive patients and those who were previously treated with a biologic in ARGO?
May I repeat the question again? I think, do we see a difference in the PsA study and the ARGO study between biologic naive and biologic experienced patients?
Not really.
I showed you this one. I mean, we will test it. The biggest thing, I think, for prescribers is TNF inadequate responders because that's still used as the first-line biologic by many. Although I have to say, my colleagues have been switching to 17 inhibitors because of the better response in the skin. And that will be interesting. Will we work in Cosentyx failures, right? I think, even there, we have a strong chance to win. From all the evidence that we have, no problem with TNF inadequate responders. I would see from the mechanism of action, no problem in 23 inadequate responders because these are really different and only partially overlapping MOAs. And as I said, even in 17A non-responders, I think we still have a chance to work.
Thank you.
One question over there.
Hello. This is Mo Jacobs. I'm a grateful physician updating the MoonLake team. I have a question for Dr. Gordon. So what would be the impact on your prescription decision and maybe to your HS physician community for sonelokimab having pivotal trials designed with HiSCR 75 as the endpoint versus other agents with HiSCR 50? And also, yesterday at AAD, we hear doctors comment on biosimilar TNF alpha will likely be widely adopted across indications. So based on the data achieved so far for sonelokimab, how do you think SLK will fit in the future HS immunoparadigm? Thank you.
Thank you. So the question is, on the one hand, the impact on or expected impact on prescribing behavior stemming from the fact that sonelokimab is the only trial aiming for HiSCR 75. And the other question, what's the impact of Humira biosimilars, adalimumab biosimilars?
OK. So first of all, I think we can go back to the experience in psoriasis and looking at our modification of our endpoint over time. If you remember, I'm old enough. Most of the people in the room are not old enough to remember when PASI 50 was an endpoint that we were looking at. And it was considered to be a good response. What happens as the metrics get better, right, we get better responses, is that everyone's held to the same standard, right? We're now asking Amgen for a brodalumab PASI 90 response. They're not all that anxious to show us that. But the point is, it differentiates medications because it does make a difference to patients.
If you're concerned about getting patients to the point, especially in this disease where the outcomes of not controlling the inflammation is so significant, as we get to higher standards and eventually it might peak to the inflammatory index of zero as the goal, physicians are going to have to respond to that in terms of this is going to be the goal. We treat. Or else we're undertreating our patients and exposing them to permanent damage, which we don't want. So I highly espouse higher endpoints. I wouldn't mind a high score 90 as an endpoint to look at too. Obviously not as many patients will get there. But it better differentiates medications. And it's getting the patients to where I can say this is the level I want you to be at as best as possible. So I think it's actually only positive.
Adalimumab biosimilars are very interesting. This disease state, I think you have to differentiate between initial treatment and what patients are going to eventually be on. So with Adalimumab biosimilars, I think there's no question for cost savings that people are going to be pushed to using Adalimumab biosimilars initially, right? That said, we've already seen the data of how many patients persist on that to one year, to six months, even short periods of time. You have a 50% response rate at HiSCR 50 to begin with. And then you look at a third of those patients are gone within six months. Well over 50% are gone within one year. And if you just go farther out than that, these patients drop off very quickly. So while I think you might have initial requirements, it might be a point of entry to systemic therapy.
But I think, for very few, that will be the point where patients end up. And so I think, from whatever impact they might have, it might be transient. And occasionally, if you can get a patient who does well and maintained on an adalimumab biosimilar, I have no issue with health care costs. I'm all for it. But the problem's going to be, are we going to be able to sustain them? And I think so. I think not. Over time, the data suggests not. And I think it's incredibly critical to think of how we treat patients, not only as, what's going to be the first thing we choose? But what's going to be the lifetime of the patient and how we treat them?
Thank you. Regarding your upcoming end of phase II for PsA, I think there's been 10 or 12 biologics approved for that indication. So what are you going to propose for your phase III plan, the usual treatment naive and anti-TNF responders? Or are you proposing something more innovative? And then secondly, would a successful uptake of bimekizumab in psoriasis push you to revisit your own plan in psoriasis?
Again, two questions there. I think, Kristian, the first one for you on whether we can share more details on the upcoming or on our proposed PsA phase III design. What will we propose to the regulators in our end-of-phase II meeting?
Let me put it this way. As much as we are for innovation, we want to take the minimum risk to get to approval. We will probably not invent the real new. Once again, for the prescriber, it's very important to have a solid study in TNF inadequate responders. That's clear. That box is ticked. I think it remains important to show effects on radiographic progression, right? It gets more and more complicated. In order to do so, you need to do this in biologic naive patients because, otherwise, you have no arm to compare to how you can protect against radiographic progression. That will be the likely scenario. If you look at the size, we probably talk about 1,100-1,200 patients.
Be assured that, when it comes to the details, when we look at the composite endpoints, for example, what are our key secondary endpoints, we will bring all of this back that we showed you today. I think, using the path to get to an approval, but do it in a way that all the innovation is not lost.
Yeah. And let me add to that. I mean, you saw, say, as the additional supporting trial without jeopardizing the main trial, the main phase III, so that it can be accepted by regulators. And important, say, as that we can compare it to all those other biologics, right? Because we have some really, really high responses. We need to be able to compare ourselves, number one, make sure that the regulator accepts it and is comfortable with it, that we're testing the right patients, and it's ethical. But also, our supportive phase II, with all the innovative imaging, that's where we want to bring something else that nobody else is bringing. So it's not through the phase III. It's actually through different actions that we bring the innovation. And I will take you to the second question, which I will play back for those on the webcast.
So, as was asking, with the data from bimekizumab, will you now go after psoriasis? The answer is no. As much as we like it, as much as that data gets us excited, as much as we know the result from our phase IIB, it is just too big of a bullet for us to bite. These are very large studies. For us, it would be a choice between doing psoriasis or doing other indications, right? So we believe that we can unlock a lot more value through the other indications. It's a bit of a shame, yes. But it's locked value that we have within MoonLake. There was one more question here.
Yeah. Samson McCullough, Citi. Just listening this is for Dr. Merola. Listening to the AAD presentations yesterday, I heard multiple presenters kind of comment that PsO in psoriasis and PsA, that a lot of the drugs we have are all very similar in terms of efficacy. And this was even referenced for bimekizumab when you just look across all the data. So I'm curious, as you look at the ARGO data, have you really elevated it? Is it differentiated versus what we have kind of hung out on bimekizumab? I'm curious your thoughts there.
Yeah. Yeah. Maybe repeating the question. I think the question is, there's a lot of approved drugs out in psoriatic arthritis. And the consensus so far is, none of them is really standing out. Or we don't see recent innovation that is really able to move things. What is our view and Professor probably Professor Merola's view on the ability to really differentiate for sonelokimab also versus bimekizumab?
Sorry. I'll answer first very basically, which is, again, just to look back at that domain chart, the very clear little green and yellow checkbox that we showed, which is just a reminder that, while there are several MOAs, right, the big ones here we're talking about from a biologic standpoint being IL-17A, then slash IL-17A/F. We'll come back to that. IL-23, TNF, historically. The IL-23 inhibitors, while I think we've made cases reasonable for probably more mild, moderate disease, I really do believe it's and we have the only head-to-head data that IL-17 inhibition really is equivalent to our and has been equivalent to our gold standard in PsA. We have the radiographic progression piece. We have the axial or spine piece. So it really checks all the boxes. But we have the elevation in skin.
So I think it's not true that the platform's even. I mean, I think, in many respects, one could make a case that IL-17 inhibition really checks all the boxes in the psoriatic arthritis standpoint, a psoriatic disease standpoint. To your second part of your question, though, I think this concept that we haven't been able to break the ceiling. I think, when we saw bimekizumab data come out at first, we were hopeful that that was going to be our break the ceiling moment. And it is phenomenal data in the skin, clearly better than TNF inhibition. But it is TNF-like effect in terms of many of the PsA domains of disease.
I was quite excited to be able to see this MDA and other composite data that really has and frankly, ACR 50 and 70 itself data that really is moving the bar higher. So I do believe we're seeing something in phase II. I hope that we will see something similar in phase III. I'm also hoping that there's something mechanistic here. And I love that they're committing to some of the imaging studies that we've been asking for a long time because we really want to have a look at whether we're having impacted sites of inflammation that aren't immediately accessible. There are entheses peripherally. There are spinal entheses. There's the entire spinal compartment, the SI joints.
There are areas here that they may have impact in a very different way. And we haven't even gotten into uveitis and other areas that may be relevant. It's a great question. I do believe I'm seeing something a little bit stand apart.
Thank you. Maybe time for one more question.
I have a follow-up. Can you remind us on the patent protection for sonelokimab and any efforts you're making to further extend it?
Yep. So patent protection, as it stands, is until May 2032 for the compound. On the other hand, we actively work on patent extensions. We just filed two new patents last year. So that could potentially bring us to 2043. I think what matters most or what we have for sure as a guarantee is the regulatory exclusivity. So in the U.S., after launch, you get 12 years of marketing exclusivity. That means you heard us talking about a launch date of 2027 for sure. Until 2039, we should be protected from any biosimilar competition. Another question would be, there has never been any biosimilar for Nanobodies. So also something to be seen. But certainly, until 2039, 2040, we should be completely fine with the potential opportunity to even go beyond with the new patents that we filed.
Looking at the time, I think we are at the end of this session. There's a few more questions that we received online that we will address afterwards. I hope this was helpful for everyone. I hope you enjoyed the presentation of the 24-week data, the presentation of the regulatory feedback, design of the HS study, the new indications, the perspectives, and reflections from our two KOLs here, Professor Ken Gordon, Professor Joseph Merola. Thank you for joining us here during a very busy week or weekend for you here at AAD. And for all of you, please join us this afternoon at 2:00 P.M. at the late-breaking session, where Professor Brian Kirby will present the 24-week data of our HS MIRA study. We hope to see you all there. And thank you for joining. Have a good day.