My name is Jorge Santos da Silva. I'm the CEO and co-founder of MoonLake Immunotherapeutics. Welcome to you all, to our Capital Markets Day, here at Nasdaq. For the many that I know are following us, through the webcast, good morning, good afternoon, good evening to you all as well. For those that are, watching us remotely, here's a quick set of instructions. If you have any technical issue, please just use the Q&A box, to signal it, and we'll solve it here on our end. Otherwise, do use the Q&A box, to send us questions. We'll do our best at the very end to address the most popular ones that we get through the platform. It's a big pleasure, to be here with you today. Now, this is a session very similar to the one we held in April, when we framed the market, and our opportunity and our expectations for hidradenitis suppurativa. For those less familiar, a very important indication for MoonLake. Today, the focus is on psoriatic arthritis. And as you can see, for what we will do in the next 90 minutes, we will spend an inordinate amount of time talking about this indication that is so critical for us as a next step. I will mention HS very briefly, but today really is about HS. I will just quickly run us through an introduction of the company for those less familiar. Also tell you a bit where we stand and what we see as our next steps and our next catalysts. It will be my immense pleasure to then pass on to Professor Joseph Merola to tell us about PsA, the disease, the unmet needs, and how the landscape for this devastating inflammatory disease is evolving. Then Kristian, our CSO and co-founder, will take us through our clinical trial on PsA, and some of the research that we think is fundamental for you to understand the disease and compare us apples to apples with others. I will come back and give you some guidance on what we expect regarding the data that we've already announced through press releases, and that will come fast and furious in October and November. And then Matthias will wrap up with a view on our financial situation. So let me go briefly through our introduction for those less familiar with us. MoonLake was founded in 2021 in Switzerland. The company was founded based on a license agreement with a pharma company, Merck KGaA, through which we got worldwide rights to an asset that we're very excited about, sonelokimab. Of course, we'll talk a lot about sonelokimab today, but we believe this is a really game-changing molecule in terms of mechanism of action as well as in terms of its molecular characteristics. On the back of that, one year later, we went public here at Nasdaq, here in the same room. And we grew, we raised gross proceeds to initiate our own clinical programs. And on the back of the HS data that I think most of you are familiar with, at the end of June, we raised almost $500 million to move these programs further into clinical development. I think that's summarized in the point on the clinical or the type of company we are. We're a clinical phase company. I think it's worth noticing that obviously we're building on very robust psoriasis data. I think this is an important source of information that many of you should be familiar with to understand how our drug works, how long the effect is, what kind of dose we go for. This is very important. Obviously, the MIRA trial, which as I told you before, read out in June its primary endpoint and we'll read out further important data now in October, and obviously the ARGO PsA trial, which we will discuss today. So come end of the year, we believe that we will be good and ready for phase III in at least three very large indications. And I think no matter how you slice it, if you think about HS and PsA alone and the opportunity there, we're talking about a pretty significant opportunity for a drug like sonelokimab. So that's the general view of the company. Why are we so excited about sonelokimab? As I mentioned, there's two fundamental characteristics that I think we will keep talking about. Number 1, we think it's the molecule that bring the right molecular characteristics to treat inflammation in many different tissues. And secondly, we believe it has the right MoA, and in doing so, marries these two sides of the coin in a way that no other molecule does. Why do we have different molecular characteristics? I think some of you might be familiar with this picture. Here on the left, you see the very massive monoclonal antibodies that we all love and have changed the landscape in medicine in the last years. But there's also other interesting molecules, in this case, the VHHs or the Nanobodies, which are the variable domain of heavy chain only antibodies. The cool thing about these very little molecules is that they retain all the desirable characteristics of a monoclonal antibody, but they're way smaller, and you can put them together. And that's exactly what sonelokimab does in a way that we don't think any other molecule does. We have two domains to bind IL-17A and IL-17F, and of course, I'll come to that in a second. And then a third domain that binds albumin, which serves as a targeting mechanism towards inflammation beyond increasing the half-life of our product. All of this together still represents a molecule that is about a third of the size of a monoclonal antibody. And again, based on all the data that we already shared with you in psoriasis, in HS, it's pretty clear that this small molecule operates at a very convenient monthly subcutaneous dose. And again, we're injecting only 1 ml of this product. So we believe that it has the right molecular characteristics to handle different types of inflammation like other molecules cannot, especially the mAbs. And it also, in our view, targets the IL-17 pathway in an optimal way. For those that are less familiar with this pathway, it is very important to know that there are 2 cytokines in this family that are pro-inflammatory. That's IL-17A and IL-17F. A and F never work alone. They work as dimers. So you have, you either have AA, you either have FF, or you have AF, as we depict up there with the little circles. Now, our molecule sonelokimab is, together with another mAb called bimekizumab from UCB, the only molecule, the only molecule that is able to inhibit these, all these three dimers, and therefore have maximal anti-inflammatory response on, in the IL-17 MoA. By the way, we showed this in April when we were here in New York. You also know that we inhibit all these three dimers with very high affinity. So that's also a difference between us and UCB's product. Then you, of course, have the more traditional IL-17 inhibitors, the what we call IL-17A inhibitors, your Cosentyx, your Taltz. These molecules can only bind A, okay? Therefore, they inhibit the AA homodimer and to a certain extent, the AF heterodimer, but of course, they cannot do anything on FF. And then there's another molecule that you guys know we follow closely, a molecule called izokibep. That molecule is also small and has an albumin binding domain like us, but it has a much narrower MoA, in that it only inhibits one of the dimers, the AA dimer. So again, we believe that we are optimally positioned to inhibit the IL-17 pathway, and we have the right molecular characteristics to go and treat the inflammation in different tissues. IL-17, of course, is a very interesting class. The broad class is expected to grow across many different indications. Here, we just show you some example of some indications where we run our own trials or where others have run trials with our MoA, and as you can see, all of them obviously growing quite a lot, but the prevalence of these indications will be mostly addressed by new IL-17 molecules. You see this in hidradenitis suppurativa, all the growth is expected to come from our category. Many notable failures from any other pathways. PsA is another good example. Several approved drugs, but nobody really driving or elevating the scores for patients the way that IL-17s do, and the same case for many other indications. So broadly, a class that is growing, and as I said before, a class where we think we are providing a very unique, a very unique solution. And why is that? And I think I think this is always an important picture to keep in mind. Why do we think IL-17A and IL-17F is truly a bottleneck between all these upstream molecules and these downstream effectors. So we believe it's rightly and optimally positioned in terms of a therapeutic solution in many of these indications. And I think the facts are starting to mount to suggest that this is indeed the case. If we look at HS, the drug that has so far produced the better results is bimekizumab. Before we showed our data in June, that clearly established IL-17A and IL-17F as the leading pathway, and obviously, as you well know, we came out with a very robust set of scores that will now be continually solidified through scientific conferences now, and additional data on the 24 weeks. But we really not only have the right MoA, but are elevating the score here. I think you've seen this with PA, with psoriasis. Fantastic results by bimekizumab, our own results. If you haven't seen it, I'll show it to you in a second. By far, the biggest deltas in terms of, of scores, especially when you're going for really the maximum level of response in the case of psoriasis, of completely clear skin. You have seen the PsA data. The PsA data, we'll come, of course, to it today again. Very clear that the IL-17A and IL-17F inhibition delivers the best balance between solving the inflammation on the joint and solving the inflammation on the skin. You see there a dashed tick. We haven't shown you the data, but we're very excited to show you the data, come, come, come early November, and obviously, a, a lot of other opportunities in, in, in many indications. So clearly the right MoA and, and clearly, when we look at the trials we already read, SLK rapidly becoming the, the, the leading drug in the leading, in the leading MoA. We would like to just quickly call your attention to our PsO data. I, as I said at the beginning, I think for the investor community and for many others, I think it's very important that everybody is very familiar with our PsO data, because I think it reveals a lot about what you should expect of the dosing and the long-term response of our molecule. We've shown that through our phase II-B leading efficacy and a very clean profile. I think there has been a question around, will sonelokimab continue having long-term responses? I think we already showed quite a bit of this data in our second paper on PsO, showing you that the duration of our response and the continuing dose benefit for some patients, or even the long-term anti-inflammatory modification that we can do in others. And obviously, a lot of work has gone into the dosing of the molecule, and are we leaving something on the table or not? I think very importantly, and perhaps sometimes less clearly. There's a lot of interesting potential in PsO also for our data. Let us show you this chart here in a little bit more detail. So there are three studies out there. One for IL-23, another for bimekizumab, as I mentioned, an IL-17A/IL-17F mAb, and of course, our own trial for IL-17A/IL-17F Nanobody. All these trials conveniently have Cosentyx, market leader, as a, as an active reference arm, and what we do here for simplicity is we basically use your secukinumab, your Cosentyx, as our, as our baseline product, and we measure how much more response do each of these drugs do in their trials compared to secukinumab. We think that this is a fair comparison. It allows us to do match-adjusted indirect comparisons between the studies, and I think the picture you see observing is that already at very high levels of response, PASI 90, you see that the A and F molecules respond actually quite quickly versus, for example, the IL-23. And obviously, over time, we all get to the same responses, but the responses are faster with A and F. But when you start going into the real maximal response, right? And again, this is a theme that for us is important, and sonelokimab is delivering on the highest scores, on the deeper responses. I think you clearly see the A and F molecules over time continue creating bigger deltas versus the standard. And here, the more you treat, the more our Nanobody gets separated even from bimekizumab, right? So long responses, deep responses, and certainly an opportunity to consider in a big disease like psoriasis. As you know, we inherited a lot of that work when we licensed the drug from Merck, and of course, we published all those results, et cetera. But as you know also, we from there decided to drive a large global phase II program to open the pipeline of indications in our for our product. We talked about a lot about MIRA. MIRA had a very successful readout. We'll come to that in a second. And again, today we'll be starting to bring ARGO, our PsA trial, much more into the fore ahead of the readout of data in early November. Just as a quick summary, from our HS data, for those that are less familiar, what we showed is that, using the primary endpoint from other molecules, which is typically a 50% improvement in one of the standard scores, we are clearly already at week 12, head and shoulders above many of the other products, with 38-point delta. And of course, our primary endpoint, by the way, the first time this primary endpoint was ever used, HiSCR 75, showing a very exciting delta already at week 12, with expectations for it to grow over time. Of course, I will not go through all the data again for HS, but important to remember that HS is not only about HiSCR. I know it's easy to have a score, and we see who's doing better on that score, but HS is a complex multi-domain disease, extremely critical to treat tunnels and draining tunnels, and I think the results we showed for our drug. I don't think we have seen them with any other drug before, both in terms of the general reductions of scores that consider tunnels. Also clear demonstration already at three months of morphological improvements on these very complex structures, and as you might remember, over 40% of the patients with no drainage anymore. So, again, fantastic results that we will complement now at 24 weeks. But again, highlighting the point that we need to think about HS across the board, not just in one score. I think the PsO and the HS data clearly position SLK as the emerging leader in what we call Type III inflammation. Within this side of inflammation, we believe that there's these verticals, Type I, where you have the macrophages, et cetera. Type II, where you have a drug leading like Dupi, and we believe that there's this whole world of neutrophil IL-17 related paths with many indications to go after, where sonelokimab is rapidly emerging as the leader. I think the perspective on our molecule, and of course, we are here to start reaffirming that into Q4 of this year, is that we really have a best-in-class drug. There's very few molecules that can compete with our molecule. Hopefully, you realize that MLTX is synonymous with running very robust, very complete clinical trials that you can do apples-to-apples comparisons with, and obviously, that we have a very big opportunity here. To finish off on this introduction, one of the things that we've been talking about is that this is our year. This is where a lot of readouts are coming. Of course, we read out in June, but also now it's gonna get quite active, and I wanna show you a view of the catalysts. Of course, as I mentioned, June twenty-sixth, a very successful HS primary readout. Today, we're here with you, as I mentioned, to talk about the landscape opportunity in HS, our ARGO trial, and the guidance for that. In October, mid-October, you should expect to see the 24-week data for HS. I will provide in one slide, specific guidance for what is our expectation. As you know, we don't hide. We, we share all our expectations very transparently with you. We will do the same thing, in early November before ACR, where we will read out our ARGO trial. That will be, discussed today. In December, we are planning to have a, an end of phase II meeting with the FDA regarding HS. So really allowing us to, in the beginning of the year, in and around, in following meetings like JP Morgan, be able to comment on how our program into phase III will look like as we build, what we think is a very, very unique, molecule for which we have a very robust clinical program, and sometimes not spoken, but very importantly, a very robust supply program as well. As we know, a lot of biologics have, have some issues with supply these days. So hopefully that provides you with a picture, of what the catalysts are and where we feel, the most critical elements for the company are at the moment. With that, I will, it's my, it's my privilege, my pleasure, to hand over to, Professor Joseph Merola. I'm not gonna go through all your bio. We would be here until next week. There are some things that I find very particular about Professor Merola. One of the few, I think the only triple board-certified physician that I know, in the U.S. He's a dermatologist, a rheumatologist, and also, an internal medicine specialist. Currently an associate professor at Harvard, the incoming chair of dermatology and the incoming distinguished professor of dermatology, rheumatology, and medicine. I hope I'm saying it all. At UT Texas, obviously a massive department in the United States, and among many other things, also the incoming president of the Group for Research and Assessment of PsO and PsA, interestingly called GRAPPA, but clearly the biggest think tank when it comes to the future of PsA. I left a lot of things out, but it's a great pleasure to have you here, Joe. My pleasure. Let's see if I can earn those titles by operating the slides. So really I'm thrilled to be with you all. I sort of have the easy job because I get to talk about what I talk about all the time and hopefully convince you of some unmet need, and how we might fill those gaps. Thank you for the kind introduction, and here we are. Let's see if this works. Those are my disclosures. You know, before I even go into this, I'm gonna take a step back 'cause I wanna just say there's probably three themes that I'm gonna try to cover. The first is that there is indeed a large unmet need in the psoriatic arthritis space. We'll talk about that and unpack it a little bit more. The other is that psoriatic arthritis really is a multi-domain and domain-driven disease state. I'll explain in a little bit, but essentially what you know what I think we've come to understand is we really can't optimize patients' quality of life and experience if we don't treat across those domains of disease. It's not just about peripheral arthritis, for example. And thirdly, that we need to break the efficacy ceiling. So we've come a very long way in psoriasis. I would argue that we have not come as nearly as long a way in psoriatic arthritis. And we'll talk about that a little bit. You know, I'm hopeful that some of the discussion today about innovating on target and structure might get us to where, you know, where we might start to do a little bit better for our patients. With that background, let me even take one more comment before what's on the slide, which is psoriasis is quite common, right? It's something like 2%-3% of the population that has psoriasis. Quite a common disease. You know, 90% of our patients with psoriatic arthritis have some psoriasis, right? That's quite common. With that starting point, about a third of our patients with psoriasis will go on to develop psoriatic arthritis. This is a number that's been recapitulated a few times, but around 40% of our psoriatic arthritis patients are undiagnosed, meaning there are a large number of psoriasis patients walking around, seeing the dermatologist, seeing other providers who have undiagnosed psoriatic arthritis. And if we take that a step further, you know, 2 in 5 patients, at least from this recent survey, are not receiving a biologic medication. And I'll take it one step further, which is to say that there's even among those on biologics, there's a limited depth of response in terms of where they're getting with their disease, and we'll cover that over the next few slides. So to that point, that psoriatic arthritis is a multi-domain disease, I'll take you on a quick tour of this, and then we'll talk about how sort of our current therapies overlay with the different domains of disease. But here you have the peripheral joint component, right? That makes sense for psoriatic arthritis. And you'll notice the endpoint here of ACR50 as a key endpoint. That's shifted over the years, right? So many of you who have followed the rheumatology, you know, literature in RA and PsA are used to seeing ACR20. I'd say in recent years, we're seeing more commonly ACR50 as a primary endpoint. Important also because it's a more clinically meaningful endpoint at present. So keep your eye on that. And the other piece of the disease clearly is skin. And again, you know, in recent years, we've moved on to PASI 90, again, as a more clinically meaningful stringent endpoint for skin improvement, and we'll see some data with PASI 100 or completely clear skin, as well. But these other domains are not a minor point, and, in fact, you know, about a quarter of patients with psoriatic arthritis have axial or spine involvement, and more than half of those patients have enthesitis, dactylitis, and/or nail involvement. And the enthesitis, just to orient you, is the site of tendon or ligament insertion into bone. It's thought to be one of the centers of pathogenesis among some, and it also may be one of the areas that it's a little bit harder for, we think, drug to penetrate, for example, which again, will become relevant to structure as we move forward. The last bit on the tour here is radiographic progression. Also important because radiographic progression correlates to damage, and damage correlates to function. And really, you know, that's just something that we look for as well in our, in our armamentarium, is are we preventing damage? Are we preventing, therefore, loss of function over time among patients? On the right-hand side-... You see that, you know, more than 70% of patients with active PsA have more than one domain. In fact, have more than, I'm sorry, two domains, which really again speaks to this point that we have to treat across multiple domains. We'll look at that, a little more in a moment. This again speaks to that point that more than 90% of our patients with psoriatic arthritis have some skin involvement. About 40% or so of them have moderate to severe skin disease. So it's not, you know, necessarily true that PsA—in fact, it's not true that PsA is living in a vacuum, and we really can't, I think, think about PsA without thinking about skin disease. And further to that, skin involvement in PsA is typically affecting at least 10% BSA, which is really, you know, moderate to severe disease, and pretty significant disease for our patients. And so, you know, we really have to think about these patients, in that way, that we have to think of across both skin and joints, and I think it's artificial for us to uncouple those two things. So this is a really nice slide. I say because I designed this slide. You're welcome. But, let me take you on a tour of this, really quickly as well. So, you know, these are the domains, so-called domains of disease: peripheral arthritis, psoriasis or skin disease, axial spine involvement, enthesitis, dactylitis, nail disease, and then this piece of radiographic progression, which is not a domain of disease, but something important in our sort of clinical, you know, considerations. So IL-17s, number one, they check all the boxes, right? They check all the boxes in terms of where we are in a domain-based approach. TNF inhibitors check all the boxes as well, but, you know, let me make a quick distinction. So I'll put my rheumatology hat on for a moment to say that TNF inhibitors have been, for rheumatologists, the gold standard for psoriatic arthritis for a very, very long time, as many of you may know. But, you know, the yellow pieces, I think, are one of the key differentiating points, is that we now have head-to-head studies that say IL-17 inhibitors are as good as TNF inhibitors, our gold standard, when it comes to peripheral arthritis, but clearly are superior when it comes to skin disease, which really matters to patients and makes, you know, what we do in the clinic, more impactful. So that's number one. Similarly in nails as well. I would argue as well that safety and tolerability are also a leg up, for more targeted mechanisms like IL-17 inhibitors when we talk about, TNF proposition, to that end. I'll jump for a moment to IL-23 inhibitors, which have been a workhorse for us in psoriasis, absolutely some of the highest efficacy in skin. But you'll see, you know, and again, we don't have necessarily head-to-head studies, but, you know, when we talk about pseudo-comparative effectiveness, you know, maybe fall a little bit short in a few areas, and have not shown efficacy in axial disease, nor in radiographic inhibition of radiographic progression. So I think those are a few of the places where, you know, this kind of overview, you know, gives us a sense of where these things fall. I also want to add that these checkboxes are true, even among TNF-IR populations and those who are on concurrent methotrexate in studies. So I think that's not a minor point when we think about where these fall in our treatment armamentarium over time. So to the point about the ceiling effect, you know, again, we've come a long, long way in psoriasis, and frankly, you know, our my rheumatology colleagues are quite jealous of what we have been able to accomplish in skin disease in psoriasis. They're also jealous of, you know, the fact that we have so many head-to-head studies in psoriasis. We have less so in psoriatic arthritis. But one thing I do want to introduce you to is this MDA instrument really quickly before we look at this data. So MDA is a pretty stringent endpoint. This is a look at a composite of both joints and skin. So sort of looking across the full breadth of all of those domains of disease that I mentioned a moment ago, peripheral joints, enthesitis, and then also taken together with patient-reported outcome measures as shown here. So quite a stringent and very much clinically meaningful endpoint. And what you see here is, you know, a peek behind the curtain of why we need new therapies and why we're hitting that ceiling. So less than a quarter of our patients with psoriatic arthritis meet these stringent endpoints, right? So 23% meet these MDA response in typical studies, and it's a nice benchmark, I think, to use when you're looking across different MoAs, different drug programs over time. Not used as a primary endpoint, but a very frequent secondary endpoint, and one that I think really speaks to clinicians and to our patients. And the PRO piece here is important because patient pain and function is included in this, and those are obviously very important to patients, and they translate downstream into other patient-reported, you know, patient experience, which are these. So in addition to obvious things like patient pain and function, I think these are increasingly have become you know have reached our awareness from the patient voice as things that they want to see in you know when we talk about new therapies and just to unpack these a little bit. So 10%-40% of patients with psoriatic arthritis experience depression and anxiety, and four in five patients with psoriatic arthritis report fatigue, which is have a major impact on their physical activity and the things that we'll talk about on the left-hand side. This is interesting because I think this has been something we've heard more about in recent years. Again, for those who follow rheumatoid arthritis literature, this has been a major discussion point among patients in rheumatoid arthritis. I think in the last few years, we've come to understand how impactful fatigue is among psoriatic arthritis patients. I even think it's starting to trickle a bit into our discussion of psoriasis patients as well, but less so and somewhat of an evolving story. You know, where does that lead us, you know, and how does that sort of impact patients? And that's here, right? Their actual experience of day-to-day life. You can see here that, you know, up to 70% of patients with reporting a moderate severe psychosocial impact with regard to emotional and mental well-being, with regard to romantic relationship intimacy, and with regard to relationships with family and friends. So, you know, the point is it quite literally hits home, when we talk about coming from skin and joint disease through to pain and function, down to, you know, how it plays out, you know, under their own roof. I quite like this data as well because we published it, right? This is all we get. You know, we get underpaid in academics. This is all I get. All right? This is my reward. So let me share with you some data. And just to orient you for a moment here to this little color-coded schematic. So what we're looking for here is we want patients to be in the dark red, right? The deeper red, the better here, which represents quality of life improvement, looking at something called the EQ-5D. And it simply says two things: that if we look across skin responses and joint responses, that we can only optimize patients' quality of life if we optimize both their skin and their joints, okay? It's a very simple diagram, but hopefully an impactful one as such. The other thing I'll say is, we didn't go into great detail, but we looked in our study at those with less than 3% body surface area and those with greater, and it turns out that regardless of the amount of skin, even when they have mild skin disease, we can't optimize their quality of life unless we get their skin clear and get their joints optimized. So it's an important sort of take-home point when we think about what matters to patients. So with that said, you know, how do we start to break that ceiling? I think over the next, you know, sort of, you know, third portion of this, we're gonna talk a little bit about how I hope and I believe that some innovations, both in target as well as structure, will hopefully help us move the needle for these patients with psoriatic disease over time, across that breadth of psoriatic arthritis domains that we covered. So to speak first to the target piece, this is a question of how can we optimize IL-17 inhibition? And so, you know, we've had in this space several IL-17A inhibitors, you know, secukinumab being, you know, one of the benchmarks there. And what we see, you know, at high level here is with a very stringent endpoint of PASI 100, again, where my rheumatology colleagues get quite jealous; this is a completely clear skin. You know, this is something that, you know, and Kristian with his rheumatology and dermatology hat on could agree with. This is something we dreamed about, you know, 15 and 20 years ago. We're talking about, you know, almost 70% of patients having completely clear skin, and this is sort of unheard of things. But we've come a long way, and what does it show us is that when we inhibit IL-17A and IL-17F with bimekizumab, IL-17AF inhibitor, we can see the added benefit in skin clearance and complete skin clearance, both at a primary endpoint as well as, you know, sustained out to week 48. So this again speaks, I think, a little bit to that target piece of IL-17AF inhibition. And then this is, you know, the question of, well, how does that translate in PsA? And again, you know, very humbly, I was very proud to be the first author on this Lancet publication of the BE COMPLETE trial. I'm gonna point out two key elements here. The first of which is, these are patients who have had—these are not bio-naive patients. These are patients who have had a previous inadequate response or intolerance to TNF inhibitors. So these would be patients in the clinic who really are already set up to have more, you know, challenging disease. And in fact, what we see here is, you know, I would say some of our, you know, better, in fact, you know, TNF-like gold standard efficacy with regard to peripheral joint endpoints. This is an ACR 50 endpoint, again, that more clinically meaningful endpoint. This is a PASI 90 response, showing some of our highest, you know, data to date in skin efficacy with regard to PASI 90. Taken together in, you know, in this PsA population, again, I think underscoring the proposition that inhibition of both A and F in a PsA population makes a lot of sense and hopefully is starting to move the needle as such. So that's the piece about target. And here's the question about structure. I think that gets, you know, has gotten us a bit excited. And these are two sort of, you know, one data point and one sort of elegant experiment I think that got me excited when I first saw it. So on the left-hand side, you can see that essentially smaller, you know, smaller molecule equals higher tissue uptake is a quick take-home message. More specifically, tissue penetration decreases 50% with every 35, you know, kilodalton change in protein weight, right? So, so that sort of makes sense in terms of why the small the size impacts tissue localization and distribution of drug. The right side is kind of cool. So what you're seeing here, and it took me a moment to visualize this, but if you imagine a horizontal cross-section of a mouse, okay, that's what we're seeing here. These are the little little paws jutting out and even a little hint of tail. On the left-hand side, you see Nanobody without albumin binding site. On the right-hand side, you see Nanobody with albumin binding site. Essentially, the take-home message here is you see more drug, more drug going to, you know, essentially the site of action, right? Where the action is here in the paws in this collagen-induced arthritis model is where the drug is co-localizing. I think to me, that's, you know, holds a lot of promise, and I think it speaks a little bit to what my colleague on the left here spoke to with some of the tunnel localization with HS, which I'll recap. But maybe might speak a little bit to some of the compartments that we've had some challenges targeting in the psoriatic arthritis arena, which are less vascular structures, things like entheses, spinal compartment, and others. I think that's where some of my particular enthusiasm is resting. Here's a place where we kinda take that, I think, together, right? So here we have a bit of an uncoupling, if you will, of, on this hand, the size piece, right? So that, tissue penetration, component, and on the right-hand side, you know, the target piece, right? Looking at that AF inhibition. So again, I'll orient you to say this is the, you know, the ACR50 response or the joint response, the x-axis, the skin response. What we're seeing is, you know, good joint response, particularly good skin response in that AF inhibition side, and perhaps, you know, a particularly good, you know, joint response here when we talk about highly targeted molecule for AA that maybe is penetrating, you know, into the place where maybe it needs to be for joint disease. And the question of, you know, what happens if we could marry those two scenarios? You know, and again, we don't have it here, but I will say if you look at the izokibep data in a little more detail, I was also intrigued by their enthesitis data that looked, you know, fairly robust. And I think, again, speaks to that question of maybe there's something about novel tissue penetration to that end. You know, here's where the question is raised of, you know, can sonelokimab be the best of both worlds in terms of what we've seen with target on the left and some of the psoriasis data with structure on the right, some of the HS data. So if we pick that apart, again, this is, I believe, the benefit of IL-17A and IL-17F inhibition when we talk about stringent endpoints like completely clear skin compared to secukinumab here, right? So there's potentially that benefit seen with skin clearance with both A and F inhibition. On the right-hand side, there's two data points. And now we're switching gears to hidradenitis. We see the HiSCR75 again, potentially showing some benefit, perhaps both because of, you know, or mostly because of structure, because both of these are IL-17A/F inhibitors. But on the right-hand side, you know, I would say this is one that I do think is particularly unique. And when we think about tunnels in HS, this is a place that has been arguably a more challenging place to show change. I would, you know, argue in some of our worst patients, where we run up against challenges with treatment, probably a place where we're even turning more to surgical interventions. But here we see, you know, in fact, an improvement in what is a very challenging endpoint. So I'm hopeful, and I think one of the questions is: Is that because of the structure getting to where it needs to be? So you've heard my voice. I have no doubt that I've went over. I didn't even pay attention to the timer, so. But let me summarize a few of the points that were made. So I think, you know, and this is important 'cause I, I, I do feel I have to own some of the patient voice here, which it translates into the clinic, which is there is a clear unmet need across the multiple domains of psoriatic arthritis in particular that really demands novel therapies. You know, I have a, I have a waiting list of patients in my clinic, granted I have a biased selection of more, you know, severe patients. But I do have a waiting list of patients who have failed just about everything that we have available and are waiting for the next thing to come. So that, to me, does underscore that there's a need. I'm hopeful that some of the innovation will come from new targets as well as structures. We talked a little bit about how A and F inhibition has the potential to optimize outcomes across PsA domains. I think, you know, that was apparent in some of the bimekizumab data and what you're seeing from the group here. I think there are also promising indications that this, you know, these smaller albumin-binding drug molecules may be able to get to where the site of action is, right? Where, where, you know, where the need is, from a tissue distribution, discussion. That sonelokimab is designed, you know, in many respects, to bring those two pieces together, both the target and the structure. I think with that, I get to take a break and pass it on. Thank you. Are you next? Yes, you are. My pleasure. Are you still good? Are you happy? All right. So also very warm welcome from, from my side. See many familiar faces here in the room. I have to say, just listening to you, Joe, I'm still absolutely excited about the chance to help more patients to really get to a higher level of response, with this drug, sonelokimab. So if I'm about to summarize, Joe, what you just said, and as you know, I'm a dermatologist, so I've been treating many of these patients for decades. ... I think this multi-domain concept is indeed something that has been overlooked. I would say that the same is true also for psoriasis, because many patients have nail disease, they have genital disease. We tend to focus on plaques and psoriasis, and ACR and PsA, and obviously, that is not what patients want. Patients want drugs that win on all the domains that they have, for very good reasons. And this is why you cannot say, "Yeah, we have a number of drugs approved in PsA." If you look at this potential of the drugs that we have to win across the domains, this is what drives the unmet need. And I would also echo, even if you have patients on biologics, we have to treat these patients for decades. Not a single patient that I have is still on the same drug after 10 years, right? So we really. There is this high need to have drugs that deliver chronic control, that are actually able to control the disease in these patients over a long period of time. What I will do is today, again, talk a little bit of science, and before we started here today, I already had some conversations with some of you, and they say, "Yeah, but the evidence and something this and something that," that is science, right? And as you move along, all you can do is look at the evidence that you have and then take these pieces of evidence to build your puzzle. You may say, "Yeah, but ultimately, it's the clinical data that needs to show me that my puzzle was pointing in the right direction." As you heard from Jorge, the PsA puzzle that MoonLake is going to show will be shown in November, right? So today, it's up to me to talk a little bit about these pieces of evidence that we currently have. And it is an evolving story, right? I will point to some of the things that are ongoing as we speak. Very clearly, what we have learned, not only in psoriasis but also in PsA, it's very clear that IL-17A and IL-17F play a role. For many years, when we talked about IL-17, what we were really talking about is IL-17A. We were not aware that there are other pro-inflammatory members. Jorge talked to the fact that these two molecules actually cooperate. On the other hand, and I find this extremely interesting, it is becoming clear that it's different cells that make A versus F. For example, IL-17A is probably most prominently made from classical T cells. That can be helper cells, the classical Th17 cells, can be Tc17 cells, so, T cells carrying the CD8 molecule. But there is increasing evidence from the last years that particularly F comes from evolutionary older cells, like innate lymphoid cells group 3, gamma delta T cells, or this mucosa-associated invariant T cells. So these are other lymphoid cells, and I come back to this in a second. TNF obviously plays a role in the various manifestations of PsA, including blunt arthritis, but also enthesitis. You talked about this. But I think there's now pretty much overwhelming evidence that TNF may be a primer for some of the target cells to then react to IL-17A and IL-17F and really drive the manifestation of the different domains in PsA. This is a very complex slide. This, Joe has already shared with you. I just want to bring now some experimental evidence that could explain this clinical chart that you saw. Now, come back to some of these cells that make IL-17F. You see this down here. Look at the Y-axis. If you take, for example, gamma delta T cells, the vast majority of these cells only make F. They do not make AF, they do not make A. So there are F-only producing cells. And interestingly, if you try to inhibit this F production in these cells, it does not work. So obviously, also the mechanisms that control A and F production among these cells varies. Now, what I'm going to say right now is a speculation, but I think it's an interesting speculation. Could it be that the failure of 23 to control F production in some of these cells is actually the reason why 23 inhibitors have been very powerful in treating plaques, but they have surprisingly failed to treat axial disease? They, by the way, have also surprisingly failed to treat HS. So is it that some of these diseases that we discuss here today are characterized by an F production that is not controlled by 23, and that is actually the reason why 23 inhibitors fail? There is also ongoing work that the receptors that bind A and F, and it's the RA receptor that binds primarily A, and it's the RC receptor that binds primarily F, will help us to understand why you need to block A and F in order to completely inhibit the 17 pathway. Now, let me take this argument to the case of psoriatic arthritis. On the left-hand side, you see a very simple staining. These are cells in an active arthritis in the synovium. These are cells that contain A. These are cells that contain F. You will say, "That's a, that's a picture we have shown for psoriasis. That's a picture we have shown, shown for HS. So clearly, there are a number of F-producing cells in the inflamed tissue, and if you do some semi-quantitative assessment, it seems to be the case, again, as in the skin, that F is more abundant, which also plays a role if you want to understand what is the totality of the evidence that F really is an independent driver of these diseases. If you semi-quantitically--semi-quantitatively assess this, you see that across various other rheumatological indications that affect the joint, osteoarthritis, rheumatoid arthritis, PsA stands out in having very high numbers of F-containing cells in the affected joints. And again, and I find this interesting, also the receptor that specifically binds F...... is most prominently expressed in PsA. I take this as evidence that, again, the FRC pathway is an important pathway in PsA. Joe talked about the fact that, of course, almost all psoriatic arthritis patients also have skin lesions. It's the same pathway. So it's probably not surprising that if you take biopsies from these PsA patients, from the plaques that they have, you find a similar picture. You find that F is there, and it's even more abundant than A. Taking this to a functional level, can we really translate this information into insight into the therapeutic potential of different drugs? This is taking synoviocytes. As much as keratinocytes are the key target cell in psoriasis, synoviocytes are a key target cell for IL-17 in PsA. So here you stimulate synoviocytes with a supernatant of what Th17 cells make. You really mimic what is going on in the disease, and you can see that some of the key markers. These are all chemokines. These are all mediators that bring more inflammatory cells into the inflamed tissue. This is why they have become the most powerful biomarkers to understand diseases like HS and PsA and psoriasis. So you see, you stimulate synoviocytes, and they make high amounts of these pro-inflammatory chemoattractant molecules. Now, you block the activation of synoviocytes by what Th17 cells make. That supernatant will contain both IL-17A and IL-17F. You block this with a potent IL-17A inhibitor, compared to a potent IL-17A and IL-17F inhibitor. And by the way, these two molecules here are matched for their affinity to A. You take this out of the equation as a confounder, and you can clearly see how much more powerful the A and F inhibitor is in decreasing, inhibiting these pathways, the synoviocyte activation that is so central for PsA. So what my learning from this would be is that, again, if you want to optimally inhibit the 17 pathway in PsA, you need to do this by blocking IL-17A and IL-17F, because the delta here is what F contributes to the disease. Apologize for a little bit, this cartoon here, but just to bring back the two molecule elements that Professor Merola was talking about. A, blocking A and F, and B being smaller and adding some evidence, again, why we think it's both elements that really matter. I talked about the A and F, so let's talk about it a little bit about the molecule characteristics. This is a slide to check whether you are really still awake, but I will walk you through this. This is the collagen-induced arthritis model you already saw, and I will orientate you anatomically. This is an inflamed joint. You see here the joint cavity, GC, in the middle, and you see this is flanked by articular cartilage, AC, here and here. So this is an inflamed joint. This is the joint space. This is the lining articular cartilage. What you see here is where does albumin sit in this inflamed joint? As you know, if you have an exposure of, of vessels to pro-inflammatory cytokines, you increase their permeability, and then albumin oozes out, and you see this albumin here accumulating in the inflamed joint. This is a picture where TNF is stained in red, the main target, one of the main drivers of psoriatic arthritis. Now, what you see in green is in the top panel, adalimumab, and in the lower panel, a Nanobody that binds to TNF that also has an albumin binding site that comes from the platform where also sonelokimab comes from. I think you see two important things. A, if you bind to albumin, that's probably not rocket science. Your molecule accumulates wherever albumin accumulates, which is in the inflamed joint. And now, probably more importantly, this accumulation of your albumin-binding Nanobody also means that you have a lot more... See all this green compared to the green here, that you have a lot more therapeutic molecules really directly inhibiting the target. So this is about optimizing target engagement by being small in albumin. You see a quantitative assessment here. We often hear the argument, "Oh, there's this company called Lake something, and they talk about Nanobodies and being small. We don't need this. "Antibodies get anywhere." They don't, right? Or show me where all the adalimumab sits here. You see a little bit of albumin here, of adalimumab here. You see a little bit of adalimumab here, but you clearly see a lot more ozoralizumab, which is the antigen-binding Nanobody by using these molecular characteristics. We think this is extremely important. You have seen this slide before, but again, just taking it now to the next level. That was a collagen-induced arthritis in mice. That is a disease driven by TNF. So what about human PsA? This is as close as you can get to human PsA. This is a primate model of human PsA. Again, I will focus on one important aspect here. These monkeys were treated with either sonelokimab, so IL-17A and IL-17F inhibiting Nanobody, or an IL-17A and IL-17F inhibiting monoclonal antibody. Yes, the Nanobody gave better clinical outcomes, but the important story is down here. In these treated animal with active PsA, during treatment, synovial fluid was collected. The question was asked, coming back to this target engagement aspect, how many target binding capacity can you find in the synovial fluid? As a marker for how many therapeutic molecules could you get into the sites of inflammation. And this is the number, this is the number here for the Nanobody. This is the number here for the antibody. Because as a scientist, you have to correct for size, right? So you see here the higher dose for the antibody in order to correct for the fact that if we just give the same dose, you would automatically have more molecules. So this was corrected here for, and you still see the massively higher capacity to bind target IL-17A and IL-17F in the inflamed joint with the, in the Nanobody-treated animals compared to the antibody-treated animals. These are pieces of evidence, right, for a role of F in PsA, for the better inhibitory effect if you block F in addition to A, for the fact that being small and albumin binding will help your molecule to accumulate where it matters and actually bind more target where it matters. Now, let's come a little bit back to the, to the clinical sites. We want to make sure that we address them in the multi-domain disease PsA, and let's look at psoriasis to start with. Now, let's try to delineate again, being small and albumin binding from having the optimal MoA. You see here the molecule that was discussed before is... This is a small ligand trap. It's not a body. It's not really an A inhibitor. It's an AA inhibitor. In psoriasis, if you look at the 80 mg every other week, you see exactly the same number compared to an IL-17A inhibiting monoclonal antibody ixekizumab. So my simple explanation here is that in psoriasis, you don't get a lot for being small and albumin binding if you don't have an optimal MoA. By the way, it's also interesting to see that this, let me call it falling short, given the theory that you would have a better response, that this could not be overcome by just giving more drug. In psoriasis, very clearly, the optimal dose was 80 mg every other week. If you would increase further to 160 mg every other week, the, in this case, PASI 90 response would not go up, but it would actually go down. Let's take this now to the disease we are interested here today, psoriatic arthritis. Again, coming back to a phenomenon that Professor Merola was already talking about, we saw with the izokibep, I think, very interesting, good data in the joint, ACR50. The enthesitis data is not shown here, but was also good data. So we feel that this indicates that in the joint, in the enthesis, when you have sites of inflammation where your molecule characteristics do matter, you seem to be able to compensate to a certain degree your more narrow MoA, if you look at what the bimekizumab A and F inhibiting monoclonal antibody can show. In the skin, you can't, right? This is from the same studies, the PASI 90 response, and you see you need to block A and F in order to have optimal PASI responses. And this tells you something about what you need to do if you want to really win across the multiple domains that we can see in psoriatic arthritis. So what is the study that will produce the data we will talk about in early November? Again, it's a large global, I think, pivotal like, and I'll come back to this in a second, phase II program. We will have the dose from sonelokimab that we know is optimal in psoriasis. We will have half the dose. We will also test the need to really have an induction scheme. As you know, we always inject every other week until week 8, and then we switch to a maintenance regimen, because at that time, your target levels are down, and you need less drug to maintain disease control. We will have an active reference arm, as we always do, in order to validate our findings. Will we be able to show phase III-like results in adalimumab, and will we, again, like in HS, be able to then conclude that we will have likely no compression when we go from phase II to phase III? But the main outcome, again, will be sonelokimab compared to placebo. The design elements are always important for MoonLake. I think in HS, the need to really design a pivotal like phase II was very high. We see many phase II studies in HS that are—forgive me, my wording—Wild West, open label, small, uncontrolled designs that you could never just take into phase III, but you would have to write a completely new protocol. I think the environment in PsA is somewhat different, but just to share with you again that we paid very close attention in order to design our study in a pivotal phase III-like fashion. When it comes to the design, when it comes to the inclusion criteria, when it comes to the geographical region, when it comes to the primary endpoint, when it comes to key stratification factors, and very clearly, when it comes to conservative statistical readouts that you will need to be able to present for regulatory approval. A little, a little comment here on the side, you see that we, for the first time, use gender as a stratification factor because there's actually very recent, very interesting evidence that in PsA, gender will be one of the main confounding factors if you look at response. And similar to what we did in April in HS, allow us to already share with you our baseline characteristics. That will not change. So these are the patients we have enrolled in our program. These are the patients that will be the source of the data we present to you in, in early November. You can look at the numbers. You see here, phase II studies, izokibep, bimekizumab. More importantly, you see here the phase III studies. If you look at gender, if you look at the duration, if you look at prior biologic use, if you look at joint count, if you look at other important factors, baseline characteristics that actually talk about these different domains that Professor Merola was mentioning. These are the patients, almost 70% of the patients, that we enrolled have significant skin disease. So we will, we will be in a very good position to actually understand the effects of our drug, not only on joints, but also in skin disease. And by the way, and I will not go into details here, nail manifestation is very important for patients. 50%-70% of patients with PsA have nail disease, and we will talk about nail outcomes in our study. So if I summarize here from my side, we continue to be extremely excited because when we look around, when we look at the evidence, we think there is really an ongoing and emerging story here that F is an important independent driver of inflammation, not only in psoriasis, not only in HS, but also in PsA. We see a lot of evidence that indeed, if you want to optimally inhibit IL-17A and IL-17F in a disease like PsA, where you need to get to the joint, where you need to get to the enthesis, you best do it by a molecule that is small and albumin binding. We see the concept that these two elements matter. We see this confirmed by molecules like izokibep and bimekizumab, but of course, we want to go beyond by actually combining these two new strategies, these innovative paths, to elevate responses. The data that we will get, we feel again, are validated data, is data that we feel will be very easy to replicate in phase III, because our phase II design is already the design we would use in phase III. Sorry. Thank you, Kristian. As we move to the final stretch here, let's unveil a little bit our expectations for the upcoming data. Now that you've gotten the full context of the disease and how we at MoonLake think scientifically and clinically about the asset. Reminder that the PsA primary data will come in November ahead of ACR, which obviously is a critical meeting for everyone involved. Again, a reminder that when you guys compare apples to apples, we are looking at ACR50 versus PASI, and we need to be comparing across many, many scores. And that this disease obviously has a clear involvement of F and also a clear need for us to not only solve the skin, but go quite deep with our molecule. Professor Merola talked to you about the large need and the large market. I don't need to go more into that. In terms of guidance, we thought that we would share with you our perspective of the market while debunking a few myths. What you see here in the screen is what you already saw before during the presentation. Joint score on the y-axis, skin score on the x-axis. You see good old adalimumab here. This is the... We're looking here at the earliest pre-specified points, be it week 12 or week 16. The clear picture is, you know, adalimumab, as Professor Merola mentioned, is still in many ways the reference. I think if you look at these primary endpoints, you clearly see that the only category of molecules that is moving away in the right direction towards that red that Professor Merola talked about are the next generation IL-17s. With, of course, bimekizumab providing IL-17A/F inhibition PASI data that, of course, is not yet created by IL-17A inhibition alone. We keep hearing about orals. Yes, the orals are approved, but of course, they largely underdeliver versus adalimumab and with some safety issues, as you know, associated with JAKs. And IL-23s, great molecules in plaque psoriasis, but indeed in PsA, underdelivering. So important to debunk this myth upfront, that it's very competitive. There's many molecules registered, therefore, you're only gonna be able to get a little bit of the market. That's true if you're competing in the middle of the pack. Not true if you're trying to go above and beyond the solutions that are in the market. Let's even bring the 24-week data. Some people only reported 24 weeks or, you know, let's give these drugs another chance. You see that none of these pinkish squares really moves towards the space that is starting to be carved out by next generation IL-17s. And in terms of expectation, very similarly to what we shared with you for HS, we expect to meet or beat the next generation IL-17s in ACR50 and in PASI 90, among other scores. So that's what we call the SLK zone. The idea is that SLK will continue moving the next generation IL-seventeens to another level. I'm not gonna go through this slide, but I want you guys to have it in your back pocket and in this document. There are many things we need to measure. Again, not just ACR50 and PASI, MDA, enthesitis, dactylitis. We just signal here for you the ones that have shown the better score. Again, for all of these scores, our guidance is that we will meet or beat these molecules. There's another myth, I think, around the market. The market may be too small, the biologics, there's other molecules, the JAKs. We tried here to summarize a few important points. You know, we take here DRG and Clarivate data. I think this is quite consistent across the board. A market that a couple of years back was about $7 billion, expected in the, as we start the next decade, to be about $9 billion-$10 billion, most of it driven by biologics and with IL-17s being the biggest category. If you just take those growth rates forward, you reach about $10 billion in the middle of the decade, which for our molecule is typically peak sales. If you look at several of you here cover the PsA space, have calculated these markets. I think it's fair to say between all analysts, all companies, all research, the market probably oscillates between somewhere between $10 billion-$15 billion, which is the same size or slightly bigger than what we predict for PsA. As I mentioned, several of these sources predict IL-17 to be the largest drug class, but most of these public sources out there don't even consider the latest data, right? So there's a lot of opportunity for this market to be a little bit bigger or for IL-17 to even be more representative once you start considering the latest data on bimekizumab, and this little Nanobody that is not yet considered anywhere, but where many, many of the analysts in this room already predict us to have blockbuster sales for. As I mentioned, when it comes to our market share, considering where we predict to land come November, I think the market shares that are attributable to us are still a little bit on the small size. I think the market is quite clearly going to grow, and IL-17s are gonna lead. So we believe that in terms of your estimations, there are many people's estimations about our potential here. We think we're likely underballing it. So we expect also this to change in the next few months. As I promised you, a very quick word on HS. I know the star of the show is PsA today, but you know, in a month's time, we're gonna have HS data. It has come up in the discussion. I wanna take you a little bit through what we expect. We show the data on the primary endpoint at 12 weeks, very early compared to many others, in June. What happened in the second part of our trial is that we continued the 240 mg dose. We continued the 120 mg dose, but now always in the maintenance monthly dose. Not weekly, not every other week, once a month. We also crossed the placebos to 240 mg and 120 mg, therefore replicating another 12 weeks of the same doses. Can we recreate what we already showed you for the first 12 weeks? And obviously, although it's a very small arm with adalimumab, can we learn something more, even if we're not shifting the patients to what is now clearly the better dose, can we learn something about what we can do with TNF patients? Very importantly, in a month's time, we will be reporting several scores, right? As we did in the primary endpoint, not just HiSCR, but everything around tunnels, other lesions, PROs. Everything you heard today is important for physicians and patients in treating this this horrible disease. What do we expect? What would we like to see in the 24-week data? Number one, we would love to see our HiSCR that we've reached already at week 12 continue to pile up, even if we're on our monthly dose, right? And ideally seeing, you know, a few percentage points that you see all IL-17s adding over time. Why wouldn't we? And we've seen that in psoriasis, but let's do this in HiSCR75 with monthly dosing. Number two, seeing great great depth of responses. We already saw, and we shared with you very interesting data on things like HiSCR90, HiSCR, IHS4, but it was only week 12. Let's give it another 12 weeks. We would expect to see that the prolonged exposure will increase these scores further and really elevate the bar even beyond HiSCR75. But our world is not only about HiSCRs. We talked about this. HiSCR does not take into consideration tunnels. HS is much more than HiSCR. So we also want to continue pushing the needle and see if we can even bring more disease control. Can we see even further efficacy rates when it comes to DT100, IHS4- 100, everything that has to do with tunnels, but also correlating that with patient-reported outcomes and quality of life and pain, which is true real-world disease control, not just comparisons of HiSCR. Obviously, as I told you, we're crossing the placebo arms, so we wanna check if we really confirm what we showed you with the 120 mg already on the first 12 weeks. As I mentioned, we would love to see sustained responses as we cross over TNF responders and non-responders. This is, of course, gonna be very important in terms of the treatment paradigm. The arm is very small. You know, HiSCR75 patients responding is only 10 out of 30. That's what you would expect. It's a very small group, but can we already have some indications from that group? And of course, very importantly, giving it another 12 weeks, do we continue to see the favorable safety profile that we saw in the first 12 weeks, especially compared to other products? So this is the picture that we aspire to see. I think you would agree that if we can hit this kind of picture, and I know we're putting the bar quite high, we will have a drug with a profile in HS, then I think the colleagues treating the real patients would say is quite an impressive profile. And that's why we believe, and we've shown you this before, that we have a small market today. We believe this market will grow. There are some disagreements in terms of whether it's 10, 12, 8, et cetera, but it's big, right? But we believe it's gonna be driven by our molecules, by UCB eventually being approved also in the United States, by izokibep eventually making it to the market, by Cosentyx, which obviously is already doing well in terms of HS in Europe, by the TNFs and other biosimilars, but also by JAKs, right? So this growth that we expect, which, as you know, is not anything unreasonable versus what we've seen in other spaces, is really gonna be driven by a lot of molecules. But if at 24 weeks we reach the profile that we showed you in the previous page, I think it's gonna start to get difficult to argue that this is going to be the drug that really delivers on all these scores and all the domains that are important for HS, as we want to do in PsA from the conversation that you saw today. So that was very brief, but obviously, hopefully, that gives you a clear picture of the SLK landing zone for PsA and what we hope to show come the 24 weeks in a month's time in HS. Of course, we need cash to do all of this, and Matthias will briefly take you through where we stand on that matter. Well, let's start with the cash, and also welcome from my side. The good news is we have cash. So you saw it happening in the last quarter. We started, ended the first quarter with $63 million in cash. Obviously, we spent some of the cash on the clinical trials that we're running, but we also raised a lot of cash, and we ended that quarter with over $500 million in cash on the balance sheet. So a very comfortable position. We were extremely excited, at our capital raise in the second quarter, not only to see continued support by our existing shareholders, some of which I see in the room here today, but also welcome some new shareholders to MoonLake who believe in sonelokimab, who believe in the value that we create here, both for shareholders but also for patients and clinicians. I think important to say, with this money that we now have in the bank, we expect that it will be more than sufficient to run the phase IIIs, not only in HS, but also in PsA, to bring us through to, to regulatory filing. Some of you saw that a bit more than a week ago, we filed another shelf registration. We also got a few questions on this one. Does it mean now that MoonLake is raising another $1 billion in cash? No, it doesn't mean that. It's a S-3 shelf registration. It means that we have the opportunity to raise cash when and if we want to, but it doesn't mean that we are now raising a $1 billion in cash. So to be very explicit on this. Now, the other side of the medal is like, not only how much cash do we have, but also how do we spend it? This looks at operating expense, and there's always a small difference between OpEx and actual cash burn because it includes share-based compensation, amortization, depreciation, et cetera. But I think whoever looks at it sees that we are fairly stable in our OpEx profile and that we are also extremely efficient and lean in our operations. We are very focused on the development of sonelokimab. We don't get distracted. And I mean, you can see here with this profile, at the moment, we are running two very large phase II studies, one in HS, one in PsA. Each study over 200 patients, pivotal like setup, both in the U.S. and in Europe. So we are running very efficiently. This will increase with the initiation of the phase III programs, which we expect to happen then towards the end, yeah, towards the end, beginning of the second quarter next year. That will go up, but needless to say, we believe that we will continue to operate very efficiently and very effectively, also compared with to our peers. Now, here, the share price. I think everyone sees the share price, and it looks great that the share price has increased. But a word of caution here also, if you look at the share prices one year ago, and you look at the volumes, there were very little volumes involved, so not truly reflective, I would say, of what people were thinking at that time, but a bit more of an artificial share price. I think the message that we want to convey here and also speaking with investors, speaking with analysts, we believe there's a lot more room to grow value for MoonLake. And I think that's also why we saw a lot of excitement in our follow-on offering. People are excited to participate because there's a lot, lot more value to be unlocked, I think, on multiple areas. I think on the one hand, Jorge just spoke about the HS 24 weeks data that will be coming up. We were really excited with our 12 weeks data, but we also hear that there are still questions. Did the MoonLake, like, guys just get lucky and, like, had yeah some luck on one arm? We will see a lot more data coming in that hopefully will put another exclamation mark behind our profile in HS. People also see a very high short interest. So certainly, there is many people that are doubting our our story. So we're looking forward to seeing the 24 weeks data that will come then in mid-October. The other element, and that was, I think, the focus of today, was really the PsA data. In PsA, we believe that at the moment, the opportunity is still largely underappreciated. What are the elements to it? I think three key elements. One of them is the market size, the other one is what's the market share that's possible for a drug like sonelokimab, and then probability of success. I think today we talked about the market size. It's a myth to say that PsA is already a very mature market where there's no unmet need. There's a lot of patients that are not even diagnosed. There's a lot of patients who are not on a biologic, and we even heard from Professor Merola. There's even patients or, like, waiting lists of patients who have run out of options. So we believe that there are significant opportunity, and that the PsA market is certainly not as mature as some people may think. We talked about competition. Yes, if you look at it in terms of number of approved drugs, number of drugs with a label in PsA, it's certainly more than in HS. But if you look at at the white space on the top right corner of this ACR PASI matrix, you see that there is a lot of room for companies to innovate, for drugs to really, yeah, address this unmet need. Probability of success, we will have to wait for our data to be shown in the beginning of November. But at least scientifically, what Kristian presented here as well, the role of F in PsA, the contribution of a smaller size albumin binding characteristics, the data that we see from others, from bimekizumab and izokibep, makes us very optimistic that we have a good drug here that will work in PsA, and that has opportunity to address some of the unmet needs we talked about. This one, just very briefly, on top, you see the main milestones. Today, it's the Capital Markets Day here in New York. In about a month's time, we will talk about our MIRA 24 weeks data, and then come the first half of November, we will talk about the ARGO PsA 12 weeks data. So a lot of milestones. Jorge mentioned earlier, we will also have the upcoming FDA end-of-phase II meeting, and we will also be present at a lot of the conferences organized by the banks. Kristian and his team will also be present at a lot of the scientific congresses. This will truly be a very eventful and very active second half of the year or remainder of the year for MoonLake. Now, the last page for me here, a little bit, some reflections on the path forward. This page we've shown in the past, and people always think, "Wow, these guys are bold, putting these bullet points on a page!" But let us be very, very clear here. We are the owner of sonelokimab, and we are well advancing with the preparations of our phase IIIs. We are planning the end-of-phase II meeting. We are very well advancing on the preparations there. We are very well funded. We raised the cash. We can drive this now, HS and PsA, and we can even drive some other indications in phase II. And we also believe that those indications are feasible for a biotech company like ours. Those are, indications where we believe we can unlock the value even when it comes to commercial. So we're executing towards the market from a position of strength. That's what we like to believe. Nevertheless, there has been rumors and articles, out there. We also truly acknowledge the possibility that this is an asset, that is, yeah, relevant and, and potentially attractive in other people's hands. So strategic interest in IL-17 and IL-23 remains high. There is a logic of synergies. We build a commercial engine or, like, even a phase III engine from stretch here, and we are a single asset company, so also something that's doable. But let's be very clear, we are the current owner, and I think also our shareholders want us to drive a company that we are running the company in a way that we are, meaning we prepare for the phase IIIs, we run for the phase IIIs. If there is something else to be announced, you will hear, of course, of course, about it, but we are the current owner of sonelokimab, and we are getting very ready for our phase III initiation and looking forward for on this path of sonelokimab. Perfect. Thank you very much. I think we have a few minutes left for a few questions. Bring the mic across. Let's start here. You, if you shout. Hi, this is Prakhar from Cantor. Thanks for the presentation. So my question is on PsA. What are your expectations on the dose response there, given HS, 120 mg seem to be the optimal dose, but there were questions about the lack of dose response? And, if 120 mg turns out to be the optimal dose in PsA as well, what will it mean for the pricing implications, given both markets have, different pricing right now? So I give you my educated guess, right? And why educated? Because we have seen the dose response relationship for 17 inhibitors across PsO and PsA before. My guess would be that already the 60 mg with induction maintenance dose could be optimal in PsA, but there may be patients, for example, those with extensive skin disease, that require the 120 mg, right? So if I can dream this up, I can envisage a world in which for the psoriatic disease complex, PsA and PsO, we have two doses on the market, but for HS, clearly the 120 mg is the winning dose. Question here. Yeah. Yeah, Tom, and then... Yep. Great, thank you. Tom Smith, Leerink Partners. Yeah, and thank you guys so much for putting this together. Excellent event. Maybe just one question for the company and for Dr. Merola. If you could just briefly review, your expectations for the top line ozoralizumab hidradenitis data, we're expecting by the end of the quarter, and how you think this will help shape the competitive landscape in HS and kind of the opportunity for sonelokimab? Thanks. I'll let you comment on that. So, yeah. I can talk about the mechanism. Yeah. So- Yeah ... first of all, based on, and I'm not even sure I should call it, and again, forgive me a little bit, my wording here. I'm not sure that I've seen HS data that I can use to interpret, right? We know that- ... that an open-label study in a small number of patients, that may have baseline characteristics that are different from the characteristics we have seen in other studies, super, super hard to say, right? I would think that if I look at psoriasis, and I showed some data today, maybe even if I look at PsA, we have the expectation that in these indications, we will, and we are better. It's a little bit hard to see how this should turn around in HS. I see the attempt to give these patients a lot of drug, right? 160 mg weekly, and this is the data that we will see in part B. That's the data I want to see in order to be able to interpret. My comment would be, look, if you want to have a successful drug, you need to win at least in three dimensions. I'm oversimplifying here. You need to win on efficacy, you need to win on safety, and you need to win on convenience. And I continue to believe that the winning way to do this with IL-17 inhibition is with sonelokimab. Anything to add, Joe? No, I mean, maybe my only comment that's not terribly data-driven, but I will say that, you know, we talked about structure and target. I think that the structure piece about getting drug to where it needs to be is very enticing to me with, you know, izokibep. I think, if anything, I would argue that not only do we need to inhibit A and F in HS, if I'm really honest from a clinician standpoint, I think the more we inhibit, the better. It's probably a, for a lot of our patients and some of our worst patients, a combination therapy approach. We probably need A and F and TNF, all inhibited to get some of those patients to where they need to be. So I still would favor, you know, broader targeted coverage of A and F, as such. That would... Again, not a data-driven comment. Kelly Shi from Jefferies, and thanks for a great presentation. To Dr. Merola, I'm curious, so between HS and the PsA, would you be able to help us to understand in which indication IL-17F plays a bigger role in pathogenesis from both scientific and the clinical perspective? Thank you. That's a tough question. I don't think I have a comparative way of telling you that. I mean, you know, you can look at tissue staining, you know, and other indirect pieces. I might take a step back to say that there are-- I think they're both major unmet needs, to be honest, from a clinical standpoint. I think PsA is probably gonna be a more of a direct and understood path for IL-17A/F inhibition. I don't yet know, again, you know, whether... There's a little bit more heterogeneity in the HS disease state, I think, and among those patients, that there may be subsets that are more or less responsive to A/F inhibition than others that may follow other paths. So I guess there's, you know, I might come in from a clinical standpoint, that the thought would be there's probably a bit more pathogenetic heterogeneity in, among HS, if that, you know, helps a little bit. But the unmet need is also massive in the HS field. We really, really need therapies in that space. So I will welcome any, you know, anything including, you know, what we've talked about today in that space. But I... There's no easy answer for you. I don't know if anyone else here has something more intelligent to say than I. For sure not. Yeah. Phil, you also had a question? Yeah. I think you have a big voice, so just go for it. Yes. Hi, Hi, Phil Nadeau from Cowen. Two questions from us. First, for you, Dr. Merola, you talked a lot about the efficacy parameters that you look at in psoriatic arthritis. Can you talk about safety? How do things like candidiasis and injection site reactions factor into your treatment decision? Yeah. Then one for the company. On the upcoming 24-week data, any plans to release the HiSCR100 figures in the 24 weeks? Yeah, I'm happy to take that first. Nice to see you. A familiar face seen a few weeks at Cowen. So let me start with the... I wanna make sure I get your question clear. So in terms of, you know, PsA endpoints, was it first that you asked about? More about safety. So you talked very- I'll go right to safety. I'm sorry. Yeah. Obviously. It's fair. So let me start with overarching safety. You know, we've done some work in this. And there are a number of registries and others that really, I think, show that some of our newer targeted mechanisms, be they IL-17 or IL-23 in that axis, clearly show safety benefit with regard to serious infection and some other serious adverse events compared, for example, to TNF, right? There's data out there that shows lower rates of serious infection, lower rates of hospitalization among targeted molecules over TNF. So I think, you know, that that's one piece, and in general, you know, and access aside, it is often our preference in the clinic to choose IL-17 and other targeted agents over TNF if we had that choice. That's more of a payer comment than anything else, right? What I have access to. You may have heard my joke in the past, 'cause I think you've come to these before, but I ask, you know, my mother versus mother-in-law drug. The IL-17 is the mother drug, the IL-17, you know, and the TNF inhibitor is more the mother-in-law drug. Okay? So, you know, a little tongue in cheek, but there is a safety benefit to being targeted. The candidiasis issue, you know, really has not raised above the surface for secukinumab, for ixekizumab. It bubbled up above the surface a bit with bimekizumab, to be fair, particularly in the psoriasis, more so than the PsA program, because of probably dosing and dosing frequency, so a total, you know, a peak exposure, I think. That said, you know, and having been an investigator on that study, I have not seen anything that would be not—that would be major or not easily treatable by a dermatologist in the clinic or rheumatologist in the clinic. So I don't see it as, as in any way, a major issue. I sort of think it borders more on tolerability than it does on safety, the candidiasis issue. And in terms of other unknown safety, you know, I think now we've had a number of years of experience. I haven't seen anything that's raised my... or piqued my, you know, concern with regard to, other, you know, malignancy, cardiovascular, et cetera, safety. So I think it's proven itself over time to be quite a safe axis to target. You know, and then, of course, you know, that, that comes against the other mother-in-law drug or series of drugs, which are the, the JAK inhibitors, so. Yeah, on HiSCR100, as we've said before, we will talk about HiSCR100 when the time is right. We have measured all the HiSCRs. We, of course, know what our HiSCR100 is. But, we will be very careful that this conversation is had once we've had opportunity to look at HiSCR100 data that is controlled by placebo and is presented as ITT-NRI, like our data. All the other data we've shared, even when people have not been, you know, showing data in a fully controlled way, but, Phil, let's not beat around the bush. There's only one company that talks about HiSCR100, and that's an open label. So when the data is there to be compared appropriately, we will show it. We will keep harping on the point that people need to show AN 100 and DT 100, and people need to show IHS4 100. We need to show that we have an effect on tunnels, Phil. So please keep flying the flag for 100% measures. Fly it everywhere, because we really need to see the effect on tunnels. Again, a patient that is HiSCR100 can be have no abscesses and nodules, but be at home, isolated, suicidal, with draining tunnels and pus coming out of their bodies. That is still a HiSCR100 patient. So until we can have a proper discussion on this, we will not show our data. Hopefully, we can move the discussion, and you guys can help move the discussion to scores that also include tunnels, 'cause that's what matters for these guys that see the patients on the clinic. Maybe a couple more questions we have? Yes. Yeah. Hey, [Evan Wang] from Guggenheim. Thanks for taking my question. I wanted to ask a question that was asked previously, but in a slightly different manner. Would you expect sonelokimab, smaller size and deeper tissue penetration, to be advantageous across a broader spectrum of PsA endpoints, beyond just skin and joint? Yeah. I mean, I'm happy to take that only insofar as I think, again, if you look across those domains of disease, the places that we've needed tissue... I believe tissue localization are where things have fallen a bit shorter, would be in some of the compartments, as I mentioned, that are, I think of as being maybe less vascular, less accessible historically, again, being in entheses, key pathogenetic site, axial compartment, perhaps synovium as well. And, you know, Kristian showed that nice figure, which I hadn't gotten the chance to see until today in as much detail, where you see that, you know, that capillary leak of albumin-bound drug sort of going to where... and I mentioned earlier, where the action is. So I'm compelled by that. Rubber meets the road is seeing obviously the efficacy data there, right? But I think it is, it is compelling to think that we want a drug in those compartments in order to check those domains of disease boxes. If you will, if you take it even a step further, you know, this is totally off the cuff, but there are other areas that we didn't talk about here, things like uveitis and other compartments of disease, where, who knows? You know, maybe small molecules over time may, may have different impact there. But I think from an albumin standpoint of where an albumin would go, enthesitis, axial disease, peripheral joints, all would make a lot of sense to me. Maybe one or two more questions. There's one in the back. Hi, Julian Harrison, BTIG. Thanks again for hosting a great event here. A lot of clinical overlap between psoriatic arthritis and psoriasis. So with that in mind, I'm wondering if it maybe becomes more worthwhile to press forward with additional clinical development in psoriasis. Or, you know, is the data from ARGO and future studies likely sufficient on the PASI front there? And then ankylosing spondylitis, Dr. Merola, we didn't really talk about it yet, but just wanted to bring it up. I'd love to hear your assessment on that need there, and if there's- Yeah ... maybe anything that could be informative in the ARGO data in November, for a path forward for sonelokimab. Yeah. Maybe you start with- Yeah, I'm happy to start with that. Yeah. I mean, as you, as you know, you know, IL-17 inhibition already is, of course, right, approved in both, in, in AS, non-radiographic axial SpA. It makes a, you know, ton of sense as you... As, as you know as well, the BE MOBILE, was it? From bimekizumab, right, looking at axial disease there, IL-17A/F inhibition also quite good. So every reason to think this is, you know, the right target for a, for A, you know, AS, for axial SpA, non-radiographic axial SpA. I am intrigued by this idea again, about whether penetration into that space may be even better. Might we even push the envelope a bit more? What we don't have a lot of in AS is head-to-head data, right? Or a TNF, you know, head-to-head data, et cetera. I think it opens an opportunity, depending on how bold folks are. I'm looking around the room, but, you know, to think about, is there something else that could be done in that space? Your question about whether you can extrapolate from ARGO is if these folks, you know, have some reasonable amount of even a hint of axial data from ARGO, like BASDAI data. It hints at efficacy. There's been a lot of pushback about whether axial PsA is the same mechanistically as axSpA, demographic axial SpA. And I think there's an argument to be made that it's not exactly the same, but there probably are some parallels. You could look at subsets of B27 positivity, for example, among PsA, you know, axial groups to try to extrapolate a bit and such. So, you know, I think, can you get a little bit of a hint? Maybe from, you know, PsA into the, into the spine. So I would certainly keep an eye out for that. But, you know, is this worthy of AS or, you know, axSpA and non-radiographic axial SpA as a mechanism? Absolutely. Which is a good transition to your question, and I think the answer will be short. As you heard, PsO is locked value in our company, right? So we are very aware of that. Let us go through the rest of the HS data. Let us also go through the PsA data exactly for the reason you're asking, and then go through the FDA in December to really understand where we are, what can we do in rheum, what can we do in derm? But obviously, we're very aware that the more de-risked we are, the more return on investment we have on all these large, larger indications. But let's let us get our house in order. Let's get all the data out there to make the right choices so that we're always the mother drug, not the mother-in-law drug, across all indications. Yeah, guys, we can take a couple more questions if... We can be here all day, but we can take a couple more questions if you- Speak for yourself. Okay. Yeah. But maybe one question there, and then maybe a couple here, and then we'll wrap up, if you guys don't mind. Serge Belanger from Needham. One question for Dr. Merola. Since you participate in the bimekizumab phase III trials, we saw some high levels of efficacy in both the treatment-naive patient population and the TNF inadequate responders. Just curious if that's something unique to IL-17A, IL-17F inhibitors, or you've seen that with the other IL-17A inhibitors? It's a good question. Well, we do see it with some of the other mechanisms. I would say there was a particular, you know, comparability between the efficacy data in the TNFi-IR and the, you know, and the bio-naïve studies that I thought was very compelling in terms of, you know, placebo delta efficacy. I think it speaks a little bit to how some of our other mechanisms, take a step back. It means to me that, you know, being a TNF failure, I think increasingly I'm convinced that I don't necessarily want to go to a second or third TNF, which are gonna be, you know, maybe could be in the future payer-driven with many of the biosimilars and such coming, as excited as I am to move to a, you know, a new mechanism when someone is a TNF failure. So I may just shift my algorithm of thought a little bit, if that makes sense. Again, I would argue, and if it were a family member, if I, you know, if I had, you know, PsA, PsA/PsO, you know, would I choose TNF over an IL-17 at the current era? I would be very pleased to choose an IL-17 first line. No, no question, for the reasons we talked about today. But I wouldn't hesitate after a failure of one TNF to go to one of these mechanisms, so... Maybe the two last questions, and then we end with Ramy. Hey, Leon Wang from Barclays. Thanks for hosting the event. I have a question for Dr. Merola. It's relating to DT100 and IHS4. So relating to, you know, these additional measures, can you talk about the role or if there's any difference between the level of evidence there for IL-17 hitting A versus IL-17 hitting F in the formation of draining tunnels, if there is a difference there at all? And also, one on PsA. So, you know, it looks like I think it's slide 25 that you have on there, that there's definitely advantages to the IL-17 mechanism. But if you had to kind of talk about your expectations on what's really driving, you know, future adoption of IL-17 in PsA, is this gonna be really their effect on the axial domain or within nails? Kind of, that will be helpful if you can frame that for us. Thank you. Yeah. I may take the second first. I'm also not an HS pathogenesis guru, so I may turn to Kristian and some others to comment on that. But, you know, what's the driver in PsA efficacy? I think what we really do want to see, there's no—I don't think there's too much excitement for isolated domain efficacy presently. I mean, I think we really want to treat across the full breadth of the domains of disease that you saw today. All the domains that were shown, and even some that, you know, that maybe weren't on the slide per se, meaning there are other comorbidities over time that I think we'd like to start to address, right? There's reason to think that many of these mechanisms address even may potentially cardiovascular and other comorbidities in the longer run. But, you know, it. ... I think to answer your question, something in the current era and in the current landscape really has to check the boxes across skin in a high efficacy way. Skin, nail, and all the other PsA compartments of disease that we mentioned. I think it would be challenging not to do that at the present time, including radiographic progression and other things that people are, you know, sort of looking for. With regard to the tunnel piece, again, I'll have to turn to Kristian to comment on, you know, mechanism. But I think that the point about the uncoupling of historic outcome measures with PROs and with depth of response and what patients need is absolutely a really, really important comment. I think that we are far from where we need to be in terms of getting patients to where they want to be in depth of response and overall numbers. So I— Do you wanna comment on the tunnel- Yes, and I'll be very brief, and I hope you also trust me to give an answer to this. So I think the evidence we have from several groups now, including the data that we presented, would point to a tunnel being really a powerhouse of inflammation in HS, right? That wasn't clear to people. You probably remember that in April, we showed you the level of inflammatory mediators in nodules versus the level of inflammatory mediators in around tunnels, and this was actually, for us, unexpected to see that the highest level are seen in tunnels. This includes IL-17F. You know that tunnels are new epithelialized structures, so the huge problem is that suddenly your main target of IL-17 is no longer just in the epidermis, the keratinocyte, but it's suddenly deep in the dermis, where normal people have no keratinocyte at all. So if you, I think, summarize the scientific evidence, that would indicate that, A, you need to have a molecule that really gets to tunnels in the first place because this is where the inflammation sits. And the available data would also indicate that, again, if you want to optimally inhibit 17, you would have to inhibit A and F, right? Now, again, if you have a drug, you need to win on multiple parameters. You need to win on efficacy and safety, and convenience. Will be interesting to see how you get there, and ultimately, the clinical data will show. But I want to say one last word because I'm not sure Jorge said it. HiSCR100. We are happy with our HiSCR numbers, but we are not happy with the perception that HiSCR100 is remission, because it is not. It's not PASI 100 or EASI 100. The inflammatory remission in HS will be IHS4 100. And if MoonLake again needs to be the first company to show IHS4 100 data, that means no draining tunnel, no nodule, no abscess, then we will show IHS4 100. And I hope you go then to the other companies and say: "Show us your IHS4 100 data," because that's what we need to do if we want to have a happy patient. Final question from Ramy. Just a quick one for me in the interest of time. I guess, based on historical data, when do you expect sonelokimab's efficacy in HS to kind of plateau? Is it at that week 24 endpoint, or do you expect it to continue to increase over time? I mean, let's obviously wait for the 24-week data. Let's see what level or additional level of HiSCR75 or HiSCR90s, et cetera, and IHS4s, et cetera, responses we get. It's not clear to us that the end is 24 weeks. I think the best is to look at The Lancet and the BJD paper on PsO. You saw that, it definitely stays into the 6 months and into the 1 year. And then depending on the patient population, you have very different behavior. But if you ask me off the cuff, do you think the movie's over at week 12? No. Do you think the movie will be over at week 24? Probably not. With that, and I know we've went over, we wholeheartedly thank you guys for, for joining us and everybody at the webcast. Thank you for joining this-