...Welcome to MoonLake Immunotherapeutics Capital Markets Update. My name is Jorge Santos da Silva, CEO and co-founder of the company. I'm accompanied here in New York by our CFO, Matthias Bodenstedt, and we have our CSO and co-founder, Kristian Reich, joining us from Europe. As you will see, we are busy activating clinical sites, so we're a little bit spread throughout the world today. Welcome to everybody. Good morning, good afternoon, good evening, depending on when you're joining us from. As you can see, we have a good agenda to go through, some very important points to hit on, over the next, roughly hour and a half. I will start by doing a brief introduction, especially for those that are less familiar, with the, the story of MoonLake.
I will then hand over to Kristian. He will give us a run through where we are with our extensive clinical program. I will then come back to hit some critical points around the markets that we're targeting with our asset sonelokimab. And then at the end, I will hand over to Matthias to take us through the catalysts, the financial position, and open for some Q&A. If you have any questions that you want to ask, if you see on your desktop, you will see that there's an Ask a Question button, so use that button. We will receive the questions out here. If you have any technical trouble or are having trouble beaming these questions to us, just use the email on the page ir@moonlaketx.com.
So again, for those that are not familiar with MoonLake, just a very quick run on who we are. The company was founded in 2021 , on the back of a licensing agreement with Merck, where we got the rights to a molecule that we're very excited about, the tri-specific nanobody sonelokimab, a molecule that is able to bind IL-17A and IL-17F, and deep in inflamed tissues. Through that license agreement, we also got rights to the nanobody technology, and you will see that we believe that nanobodies are really the next level in terms of therapeutical solutions in inflammation. The company went public in 2022 , after a founding in 2021 .
Since then, we've raised about $750 million in cash, and very importantly, we completed successfully three very large phase II Bs in very large indications in inflammation. Namely, hidradenitis suppurativa, and I will keep referring to this disease as HS. Psoriatic arthritis, which we will often refer to as PSA, and psoriasis, which we sometimes refer to as PSO. So quite a lot of work in the last few years to bring almost a thousand patients treated with sonelokimab through trials. We've recently initiated phase III in HS and soon in PSA. We'll talk about that today. And obviously, we're very excited about the molecule we have in our hands and the potential that it has. It's...
We're looking at an addressable market north of $40 billion, and we believe that our drug, even with the two main indications, HS and PsA, is a drug that can reach the multi-billion-dollar mark. What are nanobodies, and what is sonelokimab? So nanobodies really are what we call next-generation biologics. As you can see coming through the screen, you have your conventional antibodies with heavy chains and light chains. Nature, with camelids, sharks, et cetera, created heavy chain-only antibodies, which only really have one chain. And as you can see there in the dark blue, the variable region, this dark blue VHH region, is what we call an antibody, and this is the smallest biologic entity that can bind with high affinity important targets in disease.
Sonelokimab is essentially three of these VHHs put together. With two of them, we're able to bind different epitopes of IL-17A and IL-17F, and I'll come to why that pathway is important, and then there's a third VHH that allows us to bind albumin, which allows us to target this molecule deep into the tissue. The molecule is quite small compared to a monoclonal antibody. It's about 40 kilodalton. As I said, it binds three different domains, very unique domains. Nobody else binds these particular domains, and from a therapeutic perspective, it's a subcutaneous drug. We're gonna use it commercially with an auto-injector that is generally used for other big drugs like Dupixent or GLP-1s.
And you will see that the planned administration is typically monthly, which is very, very convenient for patients and physicians in therapy. Why is IL-17 important? You see it here. It's obviously a well-known inflammatory pathway, but really inflammation is driven by IL-17A and IL-17F, right? And it's when these two things get together as dimers, AA, AF or FF, that you really get the full inflammatory signal. And as you can see from the cartoon to your right, you see that only sonelokimab and one other product called bimekizumab or Bimzelx is really able to inhibit all three dimers, so really address the full inflammatory signal. The interesting thing about SLK, as we've shown in the past, is that our molecule is the only asset that can actually bind all these three dimers with the same affinity.
So a very unique molecule by all means, and within the world of two, between us and Bimzelx, also a very special molecule. As I've mentioned earlier, we've completed quite a bit of work already on clinical trials. We know that in the diseases that you see there on the left, so again, HS, PsA, PSO, and other rheumatology and dermatology indications, the leading MOA, either because we've shown that or UCB with Bimzelx, has shown that it is really IL-17 A and F. So we're talking about the best performing MOA when it comes to solving the needs of the patients.
And as you see there on the right, if you go through our trials, you continue seeing that we are the drug that is hitting the highest responses, be it HiSCR75 in HS, and we'll come more to that. Be it the highest multi-domain responses in PsA, the large deltas to competitors when it comes to full skin clearance in psoriasis, and also there's now evidence that a lot of other indications have the potential to be changed by IL-17A and IL-17F, and you will hear more about those. Very briefly, before I hand over to Kristian, some key points we will hit on today. Our very ambitious operational plan is well on course.
We did quite well between 2021 and 2023 during our phase II time. Now we've switched to phase III and more phase IIs, and the operation plan continues to follow its course, so we're very happy with that. We've had a lot of interactions with the key regulators, FDA and the EMA, on several of our programs, so we're also quite proud of that, and we will talk a bit about how that has been going, and obviously, the focus now is driving the HS and PsA phase III and adding the new indications. On HS, Kristian will talk a bit about it, but suffice to say that we are recruiting on plan.
We have our key inflection point as of mid of next year, and as I will talk about, there is a lot of signals now that indeed this is a very large dermatology market. You will see how we are differentiating within that. We will also talk about the ramp-up we're doing on the PSA trial. This program is called IZAR. You will see how the market is maturing there as well, and then, as I said, we'll touch upon. We'll start showing you where we're going with the new indications. Strong cash position, highly differentiated asset, following the plan, so we're very excited as we come to you today. Let's move then to the R&D update, and I'll pass the baton to you, Kristian.
Yeah. Thank you very much, Jorge. Also a very warm welcome from my side. Not in New York with the colleagues, but here in Europe, but still with a lot of energy. So what you see here on the next slide is a summary of what I will try to walk you through in the next thirty minutes. First of all, what is it that this pumping heart of MoonLake, the R&D engine, is doing? Number one, of course, we continue to make great progress and deliver on our phase III programs, HS and PsA. Secondly, and Jorge already mentioned this, we are opening up to new important indications: palmoplantar pustulosis, axial spondyloarthritis, adolescent HS, and I will talk about this as we move along.
Thirdly, I’m a researcher at heart, and I continue to believe that, for the size of the company that we are, we spend a big chunk of our money on doing great research, biopsy work, biomarker programs, innovative studies with innovative imaging, and of course, we would use the data that we collect there not only to feed into our medical strategy but also to create new intellectual property. HS phase III in a nutshell, Jorge already mentioned, we are actually on track. First patient was recruited in the second half, in Q2 of this year. All on track with the numbers, great study, simple design, great regulatory feedback, and we are really on track to show detailed analysis of our primary week 16 endpoint as of mid-2025.
We actually have some very intelligent brains in our company that have created a software which I'm still very surprised to see, that is fed by our friends from our CRO ICON with data that allow us an absolute unique, not only tracking but actually managing of important steps of clinical development, that really support this ambitious time plan that we have. Things like managing the contracting with the sites, managing the site initiation visits. So this is an absolute fantastic tool, and we are joking, that after MoonLake, we will probably become an IT company. When it comes to the PSA trials, we are very heavily engaged in selecting the right sites. This is a huge program with two large studies together, comprising 1,500 patients. I will remind you of the study design.
Really innovative stuff there. I just mentioned a comparison to risankizumab in patients that are insufficient responders to to TNF. And then the new indications, I will also briefly touch on what is PPP, and what do MoonLake guys mean when they say innovative imaging studies? On the next slide, you see in three circles, again, a little bit as an overview. We do this the other way around here. Most important for us remains phase III HS. And again, we are we are really proud to be able to say we are absolutely on track with our ambitious timeline. Data expected as of mid of 2025 on. The same true for the IZAR program.
You see, we have added another phase III, which I think as a physician, super important, which is adolescent HS, and the goal is here, let me say this upfront, that we go to the market not only with approval in adult, but also in adolescent moderate to severe HS, and there's a medical reason for this. Then the next wave, dermatologist that I am very close, palmoplantar pustulosis, a neglected important disease entity. We are starting a phase II study, actually enrolling the first patient in October. Axial spondyloarthritis, expected indication IL-17A/F strong. We, the best IL-17A/F inhibitor, would be a shame to not go there. And then we do innovative stuff in PsA to complement our phase III program, filling some gaps, and I will show you some examples.
Then, as I said, a broad research program, including a biomarker program, helping us to identify patient populations, helping us to identify how do we manage patients with our drug in an optimal way. We do research both from an imaging p erspective and from a biopsy, from a tissue perspective, that will further solidify the deep tissue penetration that our molecule has and then, new therapeutic areas, something that we remain very interested in, by no means is the derm and rheum program that you see here at the end for sonelokimab. HS. It is not psoriasis, and it's not atopic dermatitis. This is a disease where inflammatory, untreated inflammation progresses into irreversible tissue destruction. Why is this so important? We developed what we think is one of the best, if not the best, anti-inflammatory drug in HS.
This is so important because you need the optimal control of an HS in order to prevent this tissue progression. You see on the top right, you see a fist-sized abscess on the back of a patient, surrounded by little nodules. You see tunnels opening in the axilla region. You see what happens if you don't get the inflammation under control, that you actually end up having scars, where only surgery, laser treatments are left for the patients. This is a disease that matters. This is a disease where the strongest anti-inflammatory drug will matter in order to prevent the disease progression that normally occurs in HS. We need to deliver anti-inflammation with a drug that is safe and not only works fast, works strong, but also has a long-term sustainable response.
This is something important. We have a chronic disease here, chronic inflammatory disease, and I will come back to this, means you have T cells, you have immune cell memory involved. These patients will need sonelokimab for many years, and we want to deliver a drug that is ideal for this therapeutic situation. Last but not least, and of course, every company will say this, but I think it's absolutely necessary to say this for HS. This is an underrecognized, underdiagnosed disease. Patients stay with their surgeon, they stay with their gynecologist, with their GP. In the U.S., it takes seven to ten years before the between the first onset of symptoms and the ultimate diagnosis of the disease. We all together need to increase the awareness for this disease.
I know from psoriasis that once you have a good drug, once also patients know there is a name for my disease and there is a good treatment for my disease, that we will suddenly see the prevalence exploding. This 2% that you see here, in my eyes, is still conservative. So what do we need to do? What is it that will stop us, the progression of the disease? You see on the left side an early inflammatory nodule. You see on the right side, advanced disease. You see in the middle section, a picture from a review that MoonLake wrote together with KOLs around the world. And if you take a close look, why is IL-17A and IL-17F inhibition so important? Because this is the engine of the chronicity of the perpetuation and the aggravation of the disease.
Why? Because IL-17A and IL-17F activates keratinocytes, the main target, an important target of IL-17A and IL-17F, to release more mediators that bring more immune cells into the skin. This is why the optimal inhibition of IL-17A and IL-17F seems the most appropriate strategy to be used early on to actually stop the progression from left to right. What does it mean for us? We need to treat these patients early. This is one big reason why we do a study in adolescent HS. We need to identify patients at risk early. This is why we do a biomarker program, because we are convinced that only early treatment with a drug like sonelokimab actually has a disease-modifying effect, and this is exactly what we need.
The headline of this slide s hould be, "Why science matters?" I remember I was sitting in New York showing to you that side by side with bimekizumab, our drug, when we stimulated keratinocytes with IL-17A, with IL-17F, we had the best inhibitory effect. When we put tunnel-containing HS tissue in a Petri dish, we measured the release of these mediators that would bring more immune cells into the skin. We added bimekizumab, we added our drug, we had the best inhibitory effect. You see here that this does translate into better clinical outcomes. High score, 75 response, side by side with placebo responses in pivotal-like trials, pivotal and pivotal-like trials. You see secukinumab, left, bimekizumab in the middle, sonelokimab. HS is full of IL-17F. IL-17F has an independent proinflammatory role.
It is hard to see how you could ever have an optimal anti-inflammatory effect by just blocking IL-17A. And then secondly, you need to block A and F in an optimal way. You need to get to these deep dermal lesions, the abscesses, the tunnels, because this is what matters for patients and what drives the disease. This is our phase II data. Our phase II study was almost as large as phase III programs of others. We have talked before why our phase III will be little less, just bigger than a replication of this study. You see here our week 12 data side by side with this week 16 data of others, and I think you get where our enthusiasm comes from, that sonelokimab is really on a path to become the best drug in HS. Let's look at...
Let's take a little bit of a more detailed view. HiSCR looks at tunnels, looks at abscesses and nodules, not at tunnels. Let's see a look at deep dermal lesions. You see abscesses on the left, you see draining tunnels on the right, and you see the number of patients that with sonelokimab achieve full clearance of these lesions at week 24. So 70% of the patients no longer have an abscess at week 24. 50% of the patients no longer have a draining tunnel at week 24. I think it's important to understand, nodules are fluctuating superficial lesions. What matters for patients is abscesses and draining tunnels. But if you look at a holistic picture, let's add all three inflammatory lesions, nodules, abscesses, draining tunnels. How many patients can we bring to inflammatory remission, having none of these inflammatory lesions?
You see the answer, answer on the right, it's one out of four patients. This is what we mean by unique characteristics of sonelokimab converting into high level of responses that matter, deep dermal responses. And if you look at the IHS4 severity grades, you can actually see that more than 80% the patients enrolled in our phase II had severe IHS4 at baseline, but only 36% at week 24, again, reflecting the potential of sonelokimab to clear lesions. We allowed ourselves to create a new term, deep dermal inflammatory lesions. And we did this because we asked the question, if you go to the next slide, Josh, because we asked the question: What matters for patients? If you look at pain, quality of life, work productivity, which lesions drive the impairment there?
And it's not the nodules, it's the dermal abscesses and the draining tunnels. Let's just look at the graph in the middle. Suddenly, you see that the placebo response goes. Interesting. It's the nodules that contribute to the placebo response. Suddenly, you see no questions around the dose response. The 120 already maxes out, and the 240 cannot go above. Now, how many patients can we bring to no longer having any abscess or draining tunnel to deep dermal inflammatory lesion? Zero. You see, this is still 40% of the patients. So on the next slide, allow me, as a scientist, to do one little science route here with you. You heard that we do a biomarker proof. We saw that some markers in the peripheral blood indicate the presence of active tunnels in patients.
You can go into the tunnel tissue, you see the same markers elevate. So view here R19 and PI3 as markers for dermal tunnels. And you can see here that when we measure this in the peripheral blood, in response to sonelokimab, we can bring these molecular markers reflecting deep dermal inflammation down to the levels where they are in healthy patients. You see a nice control on the left-hand side. This is the levels in healthy patients. You see the elevated levels in HS. And interestingly, and I think this is another good reason to have an active reference in such a study, you see this is MOA specific. It's sonelokimab that delivers this molecular normalization of this dermal tunnel marker. It is not adalimumab.
I think this is what I would call the plot thickens on a clinical level, on a molecular characteristic level, on an immunologic level. We bring patients to this high level of response, including full clearance of lesion. Next slide. I call it the dashboard. Josh called it the cheat sheet, but these are the numbers to remember. Almost 60% HiSCR75 at week 24, 40% HiSCR90, one out of three patients HiSCR100 at week 25, one out of four patients IHS4 100%, and as you just heard from me, four out of ten patients no longer having a deep dermal lesion and abscess or a draining tunnel. What is our phase III program looking like?
It's a straight shootout between sonelokimab optimal dose, 120 milligrams, which clearly came out of our phase II trial, and placebo. All the great values that we showed you were week 12 values. Now we go to week 16, of course, giving our drug more chance to really deliver, especially on the high level of response, and then the placebo patients are crossed over to sonelokimab. We use our established induction and maintenance schemes, so every other week until week 6, and then monthly from week 8 on. So the maintenance dose, monthly injections. 800 patients across two identical studies, clearance from the FDA and from the EMA. The study has enrolled the first patient in May this year. It will start enrollment in Europe soon.
Everything on track, pretty much identical to our phase II program, with slight nuances that we think, if anything, give us an even better chance to show the separation from placebo we saw in our phase II trial. The study is happening east and west of the Atlantic, the U.S., Canada, and in Europe. Of course, all the great sites we had in phase two, in phase II are again on board. We have regulatory clearance, as you heard. Allow me to make one little comment. I heard some rumors that, "How are the MoonLake guys going to achieve this fantastic enrollment times?
How is it possible that they can report about their primary endpoint as of mid of next year on?" And just to give you the facts here, our expected recruitment rate, what we calculated with in phase III, is zero point three five patients per site per month. The industry standard is zero point two six. That's true, but what we had in phase II was zero point four five. So we did not even assume the actual enrollment rate we saw in phase II to calculate the numbers and the timelines that we share with you, just to be very clear. Two identical studies, all on track, so be excited as of mid of next year on to hear a more detailed analysis of the primary endpoint.
This easy study design allows us to go quite far in what we can say from the primary endpoint data. And you see here on the right-hand side, all the familiar endpoints. We continue to be a HiSCR75 company. We will look at IHS4 because we want to look at inflammatory remission. Of course, we look at quality of life, and pain. You see the timelines here again, as I said, I repeat it, as of mid of next year on, we will be able to deliver details on these endpoints that you see on the right-hand side. We are known for selecting our sites very diligently, train our sites very diligently. I participated in the investigator meeting in Chicago recently, where Alexa Kimball and her team did the training again. We do a very meticulous monitoring of data.
Of course, we do everything we did in phase I and even more to ensure a high quality throughout. So what do we look for? What can we expect? And just as a reminder, you see here the bimekizumab, adalimumab, and secukinumab, high score seventy-five delta to placebo data from their pivotal phase III trials, and they had two phase III trials each. So this is why you see the two numbers here, and then you see the average in the middle. So what is to be beaten is 17.5, and we would think that any delta high score seventy-two, high score seventy-five to placebo, higher than 20, we would call this a real win. Now, I remind you, this is week 60. Our real delta high score seventy-five to placebo at week 12 in phase II was 29%.
Interestingly, also, that when you discuss with KOLs, and we are starting to do our KOL surveys, unbiased KOLs are even a little bit more humble and say: "We would currently call a drug that produces an 18.5 delta HiSCR75 to placebo, we would call this drug a gold medal drug." So looking at all these numbers, we continue to be confident that we have a very high potential to deliver the best delta HiSCR75 to placebo that has ever been shown in a phase III program in hidradenitis suppurativa. Of course, we not only do good things, we also talk about it. And as a spotlight here at the upcoming EADV conference, we will present five abstracts. Three of them have been selected as oral presentations. It's a nice blend of basic science work, of translational work, of new clinical outcomes.
I love to go to these conferences because we are bathing in a wave of excitement of the KOLs. We do this work together with some of the finest KOLs around the world. You see here, Martina Porter from Harvard, from Alexa Kimball's team, delivering. You see Brian Kirby from Dublin, one of the stars of clinical trial development in HS presenting, and also, I was allowed to give a presentation on science. So I really look forward to the EADV, and we continue, I think, to have a very strong presence at all the major important conferences. PSA, and you saw on the previous slide that we also bring PSA to dermatologists. Why do we do this? Because MoonLake is the company that sees, views, perceives PSA as a true multi-domain disease. This matches what physicians and patients think about the disease.
The two main domains being the joints and the skin, which would be reflected by ACR and PASI. But don't forget, there are additional domains, the nails, the enthesis, axial involvement, pain, other patient-reported outcomes. If you look at the MDA, Minimal Disease Activity, you actually find seven parameters that you need to hit across all of these facets to be able to call a patient, "Yes, this patient has achieved MDA." Why do we focus on this? Because we want to explain why we show ACR plus PASI, why we show MDA response, because we think that these outcomes optimally reflect what is really going on with this disease. Just to remind you, and here are now these outcomes, that we saw very high, very promising composite outcomes.
MDA 44%, ACR50 plus PASI100, more than one out of three patients, and even ACR70 PASI100, almost 30% of the patients. You see the data of the adalimumab reference side by side. But of course, like in HS, this doesn't stop at week 12. So when you look at the week 24 data, we see that these outcomes continue to increase. This was not a head-to-head trial. Let me be crystal clear. But in this study, we had an equally sized adalimumab reference arm. I hear people saying, "Yeah, sonelokimab did not really differentiate from ada-." We think we absolutely differentiated from adalimumab, especially in these outcomes that matter. And you see here the delta to adalimumab in MDA, in ACR50 PASI90, in ACR70, and PASI100 at week 24.
So interesting to see that when we talk to rheumatologists, I dare to say that the excitement levels are almost higher, if, if this is possible, than they are with the dermatologists. And I think it's due to the slide that we are just looking at, that here's a drug that delivers high outcomes at this multi-domain nature of the disease. So what will the IZAR program look like? And fundamentally, we do innovative stuff, but we also do the stuff that is regulatorily required. So we will do one study in biologic-naive patients, where we will also look at radiographic progression. You see this on the left-hand side. And we will do one study in TNF inadequate responders, and I think here is a real innovative element. Why?
There is a real question out there: What is the best MOA to go to in a patient that has failed a TNF? Should we go to an IL-17, or should we go to an IL-23 inhibitor, such as risankizumab? We actually see a very strong presence of risankizumab in the PSA market, and our study will deliver more data to give an answer to this important question. Of course, you see the 60 and the 120 milligram dose both being tested in the clinical trial program. These are large studies. All the outcomes have a 90% plus power, including the radiographic progression. This is not a true full head-to-head, but there will be some real head-to-head comparisons possible vis-à-vis risankizumab.
and with a whole program of 1,500 patients starting at the end of this year, again, we think we will add a major milestone to the treatment landscape in PsA. We are in the two geographies that you know from our HS trial. We add another geography, which is South America. South America has been doing great in recent phase III programs, especially when it comes to trials where you need to enroll biologic-naive patients. And if you are in doubt, do these MoonLake guys exaggerate? Do they see a real chance in some selected head-to-head outcomes to win against risankizumab?
Just as a real little reminder, the third bullet point on the right, when we look at the phase III PsA program with risankizumab, when we look at our own ARGO data, again, we think that this study has a chance to deliver the answer, who is better in TNF inadequate responders, sonelokimab or a drug like risankizumab? Currently, the team is fully engaged in site selection. You heard from me how serious we take site selection. This is all ongoing. Several hundred sites have already been identified. Again, our phase III program will fundamentally replicate the endpoints we looked at in phase II. You see them depicted there on the right-hand side. We are the ACR 50 company when it comes to PsA trials. We will add high levels of response, MDA. We will, of course, look at patient-reported outcomes.
We will, of course, look into the skin facet of the disease in one of the studies. As you heard me saying, we will also measure radiographic progression, all in the plan to have the first patient in the US at the end of this year. And then you see that the timelines that follow with the first readout, approximately six months after the readout of the HS trial. As you heard me saying, it's not only a pleasure to go to Germany, even a pleasure for me as a dermatologist to go to rheum congresses. And the reason being that this nanobody nature of sonelokimab is really viewed as an opportunity to get drugs finally into anatomical structures that matter, like the entheses.
So it was fantastic to see how the presentation of Professor Iain McInnes, Professor Georg Schett, how their presentations were reflected. Professor Joe Merola, who's a dermatologist and a rheumatologist in a good position to specifically talk about the multi-domain nature of the disease, and our big presentation of the week 24 data will just come later this year at the ACR. Let me take a quick step back and talk about the science and why we think that by no means is HS or PsA the end for sonelokimab. If you look at a group of chronic inflammatory diseases, you see many upstream events, including innate immune events, like the release of IL-1, that have a chance to activate multiple cells.
You see their adaptive T cells, but also evolutionary older innate lymphocyte neutrophils to make IL-17. And then IL-17A and F, again, do many things, and I mentioned the activation of chemokine production in keratinocytes. So if you look at this, it becomes obvious that the inhibition of IL-17A and F is actually the pathophysiological bottleneck of this group of diseases. And again, HS and PsA are just two members of a longer list. You see on the next slide, a visualization of some of the discussions that we had. And of course, you see HS and PsA there. You see ankylosing spondylitis, non-radiographic axSpA, you see PPP, but there is no end in the list of indications where this type of inflammation, and therefore, also an optimal inhibition, an optimal therapeutic effect of sonelokimab, is obvious.
Which are we going to attack? If you go to the next slide. Palmoplantar pustulosis, I will explain to you what this is. Forgotten disease entity, no drug specifically approved. Market size, at least $3 billion. This disease can come with or without psoriasis. We already know that we work beautifully in psoriasis. You heard from me that if you want to treat earlier in HS, you need to ideally come with an approval in adolescent HS. This is another adding another market of $1-$2 billion. No drug has been explicitly studied in adolescents so far, and then, of course, two big rheum indications, psoriatic arthritis I talked about, but we want to add axSpA, with an equal market size to our list and opening the door for a phase III program in AS. Now, what is PPP?
Palmoplantar pustulosis, and guys, you better get ready for this. This is going to be huge. You see up, on the, on the upper right-hand side, this is what classical psoriasis looks at the hands and feet. This has nothing to do with PPP. PPP is a disease that has pathophysiological overlap with psoriasis, but is a disease in its own rights, where patients have a very different clinical phenotype. The accumulation of neutrophils in PPP is so strong that you begin to see the pustules with your naked eye, and if you take a biopsy, you can actually see this massive sterile accumulation of pustules in the upper epidermis. Interestingly, classical antibodies have struggled, and we actually think that the limited penetration of full-sized antibodies to the upper epidermis may have contributed to this limitation. Prevalence is estimated to be as high as 0.3%.
In the US, around 60% of the patients also have plaque psoriasis on their body, and if you look at the picture, you will understand they can't use their hand, they can't use their feet. This is another chronic inflammatory disease that requires a strong systemic anti-inflammatory treatment. I promise this is almost the last slide on science, but I, I couldn't stop it because I want to show you how we work, how we think. So what's the, what's the latest hypothesis? Why do patients have PPP? The idea is that T cells come in, T cells make IL-17A and F. As in HS, this A and F induces in keratinocytes the production of chemokines that attract neutrophils and more neutrophils.
And now another vicious circle starts, in which neutrophils release interleukin-19 that drives specifically the release of a mediator that attracts more neutrophils, and now you can understand this massive sterile accumulation of neutrophils. I have already shown you how good sonelokimab is in not only reducing IL-19 activity but also bringing IL-19 down. So I would say PPP is almost a biomarker-selected indication for sonelokimab, with very high probability to see a good response. We do this open-label proof of concept study in PPP. First patient expected to be enrolled in October. These are sites in Germany that also participate in our VELA, our IZAR programs. These are expert friends, if you will. We do an extensive biomarker program in the peripheral blood and in biopsies alongside the study.
A major endpoint will be the reduction of a specific score developed for PPP, which is called palmoplantar PASI, and we want to actually measure. We want to see how much this PP PASI decreases from baseline. Primary endpoint will be at week 60, and of course, since we know our optimal dose from psoriasis and HS, easy to pick the 120 milligram for this study. VELA Teen adolescent HS, regulatory authorities gave us green light to do a small bridging study in 30 to 40 patients. Again, no requirement to do this placebo-controlled. We can go ahead, open label. 120 milligram is the dose. Again, sites that we know, sites that participate in our other programs. We will do an extensive bridging work when it comes to specifically pharmacokinetics, but of course, we will also look at the main clinical outcomes.
We do this study in the U.S. exclusively, and we do this in very close collaborations with pediatric dermatology experts such as Professor Amy Paller from Chicago. The study is all set up to produce data at the same time that our adult study reads out, so that we can feed the adult and the adolescent data into the BLA with an eye on getting an approval in both indications at the same time, adolescent and adult HS. Now, on the next slide, just very briefly, I remember that I presented the PASI to you at a previous time point, and we were saying, "What is this score? You press, and patients say, 'Ouch,' and then you get the one." And we said, "It cannot be.
MoonLake needs to be better." We actually connected with some of the finest KOLs when it comes to imaging, and we arrived at what I think are two very innovative imaging studies with specific tracers that allow us to not only measure osteoblasts, which activity, which is very relevant in axSpA, but also fibroblast activity, which is very relevant in PsA. These tracers will give very sensitive signals at any site of inflammation in the sacroiliac joints, in axSpA, in fingers, in the enthesis, in PsA. So now, for the first time, we can really not only see what is our nanobody doing at these deep sites of joint inflammation, we can quantify it. We can really measure precisely the scintigraphic signals.
And I think in addition to the phase III program that we do, this will do two things: It will open up in axSpA, but will also close some gaps and really bring a different quality of data in PsA. So this is the last slide, and I know that when my clinical development team sees this, they will take a deep breath in. But this is actually what MoonLake is doing. So not only do we have four phase III trials, two in HS that are running, PsA, two trials that are starting this year, a phase III trial in adolescent HS, but we also have beautiful trials in additional indications, palmoplantar pustulosis, opening phase III in PPP, in axSpA, opening for phase III in axial spondyloarthritis.
And I think we are very proud that we are actually able to unlock all the potential of sonelokimab across these various derm and rheum indications. Thank you very much.
Thank you, Kristian. That was great. And by the way, for all those watching the session, all these slides and more will be available to you, as are already in our webpage. So don't worry if you didn't get all the details. As you know, we always like to share a lot. Today, we showed you some of the new data that will be doing the circuit of all the scientific conferences over the next weeks and months. We showed you we hadn't done this before, our IZAR plan where we stand with the regulators on both trials. We showed you the designs for two of the new indications. Kristian started talking about Solaris and Polaris, our new indication trials for rheum. We will be sharing more detail on that.
But as you can see, and I think a big shout-out to the whole MoonLake team, many of which are watching this. It's an amazing effort that the team has been doing. This is really record-breaking clinical development here. And we'll be looking forward to share more about how we progress through those ends of those phase IIIs and those phase IIs. The next element that we wanted to share with you is our view on the market. I think there's a lot of opinion out there, and in good MoonLake style, we wanna give you a bunch of facts, so that we can talk with real numbers about what's really happening in the market.
And let me start with HS, which we really believe is a franchise-building indication because of the size of the market and the potential we have to make a change with sonelokimab. When we talk to investors, The Street, and many other players, we hear essentially three questions, and that's where I really wanna spend a little bit of time on. One is: What makes us believe that there is really an HS market here? And we will be telling you that indeed, there's now a very clear indication from two competitors of ours, Bimzelx, but also Cosentyx, that indeed, there is a market here, and that market is big. Two, why can this market be so large? How come, you know, two years ago, we didn't really hear much about this market, and now we're talking about many billions?
I think we'll show you evidence that indeed, there is larger than expected prevalence, but also there's a pricing and a biologic treatment element that really drives this market along other big dermatology markets. The third question we hear is: How can you, as Moon Lake, win with sonelokimab in HS? We'll share a few views on that. Let me start with the first question: What makes you believe that this market is there? As we said before, we believe that by 2035, this market will be up to $15 billion and even more than that. The first time we showed you that, there was a lot of question marks about, "Where do you get these numbers?
Are they real?" We're very happy to see that our competitors are also starting to put their own projections in the market, and they're also starting to get to the same numbers as we get to into the next decade. How is this market driven? What you see there on the bottom, the market today has been driven, or until recently, had been driven by Humira. Humira is not a great drug. It has very limited durability of response. That's one big Achilles heel, and obviously, the response is not fantastic. 50% of improvement for 50% of the patients. Very recently, Cosentyx launched, and you will see that the acceleration of the market is right there. However, Cosentyx, as an IL-17 A only inhibitor, is in itself a limited drug. Kristian already showed you the numbers.
There is more durability of response. That's good in terms of the therapeutic solutions, but when it comes to efficacy, we're very limited. The market is then driven essentially by two players, in our mind. One is Bimzelx, which we expect to launch sometime next year. That's one of two IL-17A and IL-17F inhibitors. And then there's us, the other IL-17A and IL-17F inhibitor. But as you saw from the numbers, many reasons to believe that we will present a therapeutic solution to the market that accumulates a lot of characteristics, from response to convenience, to elements of inflammatory remission, to safety, to switching profiles, that really create, in our mind, an opportunity for treating physicians that I think drives a lot of the excitement that Kristian mentioned when referring to colleague KOLs.
So when we think about what needs to happen to show everybody that it's not just us saying that the market is big, indeed, we're looking very closely into Cosentyx and Bimzelx, both on the U.S. side and on the European side. And today, I wanna talk a little bit more in detail about what's happening with Cosentyx in the U.S., and a little bit about what's happening with bimekizumab in Europe, as an indicator that indeed things are traveling in the direction that we've been working on. So this, I think, is an incredible picture. We know that Cosentyx is a very large drug in inflammation.
It has been very successful for many years, since, I believe, the launch in 2016 in psoriasis, which was the first real move into dermatology from Novartis. But the drug had been struggling in the previous quarters, right? And what you see in Q4, as Cosentyx launches in HS, in the United States, the turning of fortunes of a very large molecule, right? So HS in the US single-handedly contributing to the growth of this big blockbuster. And indeed, these days, even the company that drives Cosentyx, realizing that HS is indeed the second biggest indication for its drug. What is actually happening?
How is this turning of events changing in the market? And what you can see here is analysis from our claims. I remind everybody that we monitor about two hundred and fifty million American lives. We do this on a daily, weekly basis, so we see everything that is happening with all these individual patients, which you will agree cover the majority of this country. And you see that Cosentyx is making a big inroad in terms of new patients. So as of the last read, about two-thirds of new patients are started in Cosentyx, which is good because, of course, we have a high unmet need.
There was obviously a very big care gap. Only Humira was there, so a great new opportunity for physicians and patients. And you see that Cosentyx is slowly but surely grabbing the total market as well. Despite all this limited efficacy that Kristian already talked about, despite the fact that it's eight years launched after Humira, it's still there. But what you see is that, obviously, there is space for drugs that innovate, but obviously, clinically differentiated products, which also present durable options, are probably gonna rock the market, in the near future, and obviously, that's IL-17A and IL-17F inhibitors. Another interesting cut that I think is quite interesting is that half of the patients that drive the Cosentyx sales are biologic-naive patients.
So we're bringing new patients, previously untreated, probably some of them undiagnosed patients are coming in, but it's not just about new patients. We have about 40% of patients that were refractory, i.e., had been treated with Humira before and, you know, no longer could see a response. And you already see a healthy amount of switching, which I think if you take it as a whole, really shows a very healthy contribution of this new drug to the growth of the market, right? So if you look at the Cosentyx patients per month, we see already in June, over 5,000 patients. There's a continued increase in the total number of patients.
Even if there was an initial bolus of patients that had been, you know, TNF-experienced and waiting for this solution, we see a lot of new patients coming in every month, and probably these recent months, we were looking at June, are probably even underestimated because, of course, it takes time for many patients to get their claims processed. So this number, if anything, is bigger than that. For those that believe that Cosentyx has plateaued somehow, we just don't see it in the daily claims with people that are getting real drugs and insurances that are paying real money. What is happening in Europe with bimekizumab? Kristian mentioned that we're running surveys with HCPs in both sides of the ocean.
There was some interesting insights around what they expect to see from us, and Kristian shared that. Here, we're showing you a cut of German physicians that were surveyed by us, a very large number, to see what's happening with Bimzelx in Europe. You don't have the claims data in Europe easily accessible, so it's not as easy to measure. But we're already seeing that about 20% of biologic-naive patients are already being initiated as of now in Germany with Bimzelx, so great to see this. And the physicians expect some growth over the next twelve months, and 40% of people that were already in biologics are already being treated with bimekizumab, right? So clearly, they're rapidly capturing market share in Europe.
They're building on the early momentum, also driven by the success they have seen in PSO. Clearly, a high interest on IL-17A and IL-17F as the winning MOA, but also very interesting for us, and I think you saw it, when Kristian mentioned that, the expectation is still there for more. People see bimekizumab as a great solution, but clearly not yet the game changer. So we're very excited to bring bimekizumab soon enough to the market. The other question is: Why is HS such a big opportunity? I think people ask often this question: why is it so big?
And I think in this simple design that you have, on the side, here on the left, I think illustrates this point, right? So if you look at PSO and, atopic dermatitis, you see these are big markets. They obviously are high prevalence diseases. But what you see with HS, is that HS has a prevalence that is quite similar. I mean, we're talking about 2%, and we will show you more numbers on that. But very importantly here, HS is also double the price of what you would expect, in PSO, because typically you're double dosing, PSO doses, right? So it's important that we consider this, because this is something that really drives the size that I think often gets forgotten.
What you can see there is already that HS then rapidly becomes an indication that is as big, at least as big as atopic dermatitis, right? When we think about this, these elements in terms of prevalence, what you can see is that in terms of prevalence, we're at the 2%, we're probably even being conservative. Sorry, I'm having trouble moving my marker here. What you can see is that because HS, as you saw also from the pictures that you've seen earlier, probably has a much higher share of moderate to severe patients than PSO or atopic dermatitis. As of today, the penetration of biologics is very low.
So if you wanna think about what drives this market to be this size, it's really these three factors. It's the prevalence element, which KOL literature places anywhere between 1% and 4%. It's the price level. Don't forget that the price here is double that of psoriasis, and we really have a case for biologics. There were no solutions there, and the penetration as is is extremely low. Let me just deep dive into a couple of these points. Let's come to prevalence. We showed you this picture in March when we did our R&D day in San Diego in the context of the AAD. We showed you some very impressive numbers. There's two million Americans that are diagnosed and treated for HS, so an existing market already there.
We showed you that on average, over the eight years of longitudinal claims that we have, we see roughly two hundred and fifty thousand patients, new, every year that are being diagnosed and treated. That you already start seeing some patients treated with biologics, but that that share is very low and it has been driven by a less-than-ideal drug in Humira. That was the Q4 numbers when Cosentyx was being launched. Now, what happened since then, in two or three quarters, is already palpable impact, to show you how big this disease really is. Since then, about 10% more patients have come to the population of those that are treated, after diagnosis.
And if you annualize this rate, we're probably gonna start moving from 250,000 patients new every year to 300,000 every year, just based on what we think is the launch of Cosentyx. And therefore, no surprise that Cosentyx is probably gonna do $1 billion in its first year of launch. So if you have any doubts about the market, I think that tells it all, and I would argue, at least personally, that this was not necessarily an indication that Novartis really powered up in terms of market preparation. And what you already see is that more patients are being treated with biologics. You already see the increase in biological treatment. So clearly, the patients are there. But here, we are talking about diagnosed and treated patients today, right?
That's about 1% of the U.S. adult population, if we look at the last eight years of data. But again, these are diagnosed and treated. What do we expect to see in the next years, in terms of the diagnosed and treated patients? If we simply assume a historical average growth of 200, about 250,000 patients every year, we very easily, without any additional growth, see about 5,000 patients when 2035 comes around. In addition to that, there's a lot of patients that are already in the system. We see it in the claims, we see it through work that has been supported also by Novartis, that there's a lot of patients out there that are already having HS-related surgery or have lesions associated with HS.
And this is roughly about three and a half million patients that are probably just on the cusp of being diagnosed and coming into the market. So it's really not difficult to imagine that we probably have eight or more million patients out there in 2035, and that indeed estimations of prevalence around the 2% are more than justifiable. In terms of biologic share, I think here we show you how that has progressed over the years. You see there, Cosentyx approval on Q4 2023. That immediately starts driving growth.
You see that Cosentyx grows the market, and together with biosimilars, we believe they both eat a little bit into the Humira share, whereas other drugs that are used on the side really don't move much, right? But Cosentyx clearly growing the market, clearly increasing the biologic share. Humira losing market and of course, bimekizumab and sonelokimab expected to be the next inflection points in growing this market, and obviously a lot of potential, right? 3% biologic share but versus what you would expect to be about 15% or more in other indications, clearly tell you that again, this can really drive the growth of the market. And last but not least, the price level. I don't wanna dwell too much on this, but we want to leave you with the facts.
You can consult them later. In HS, the price is double that of PSO. That's the way it has been. It's the same way in the U.S. and the same way in Europe. We have the advantage that we will launch HS first. We don't have a psoriasis launch in on the back of us, so of course, we will have a lot more freedom, but this also drives the size of the market. And that's how you get to a market that is probably the size of the AD market. Very briefly, I won't go through all the details here, but the third question we keep hearing is: How can you guys win in HS? You're an upcoming biotech. There's a couple of reasons to believe.
Number one, and this is just a reminder, we've talked about this several times before, HS is not a winner-takes-all market. In fact, none of the immunology markets are winner takes all. Typically, the four top drugs in any of these indications, we have an example with psoriasis, typically make $2-$3 billion per annum. But you have a long list of other molecules that are in the market. The same case for PsA that make $1 billion. So the markets can really accumulate a lot of drugs because as you see, as you launch, the market grows, the market takes more innovation. It's not just people moving shares. And obviously, the new entrants and new entrants drive growth, and you see that with HS as well.
I'm not gonna go too much into the detail there, but we've left you some numbers to debate. Any database that you look at will give you this answer. What we also see in all these markets is that differentiation really matters, right? Every time you have a drug that delivers a different benefit-risk profile, you see the sales growing, and we will show you an example for PSO. Obviously, we have a very clear profile or a very clear potential profile of an improved benefit-risk ratio. Very interestingly, I will talk a couple of minutes about this. The access around HS is different from other indications, and I think it favors a new player, or it favors somebody that is not necessarily just a powerhouse in immunology.
One of the critical elements there is, of course, that the conditions, the criteria by which these drugs are analyzed, depend on the disease, and HS is very important criteria versus, say, an indication like psoriasis in terms of its severity, irreversible damage, et cetera. But also HS has very limited Medicare Part D exposure. And this is important for all of those that follow the impact that IRA has in the market. This is, we think, a particular differentiating element that I will also share a bit more on. And then I think we've talked about this before. We won't talk too much about this today. HS is highly concentrated. Again, about 70% of patients are with 10% of the physicians, right? So it's highly concentrated.
So when you think about a go-to-market model, an approach that is very targeted in, for example, in the U.S., in the main cities in the U.S., will suffice. And of course, on top of all of this, the market has all the conditions, but let's not forget that we really have a drug here that can become the gold standard, and obviously, that will facilitate any winning that we do, with sonelokimab HS. Let me just highlight a few points that I think are important, and again, facts to drive the discussion as we have it in the market. One of the elements I wanna pull out is that efficacy matters, so this benefit-risk impact matters. You see there in the light blue, the Cosentyx launch.
Novartis was its first move into immunology at the time, so you don't have to be a big immunology player to actually come into the market and win. You have to be a good player, and Novartis obviously showed that with Cosentyx back in the day, and you saw that the market grew on the back of that. Then Skyrizi came along, right? Another interesting drug for psoriasis, and you see that again, the market didn't shrink. Shares didn't necessarily move from one place to the other. There is some of that, but mostly there is growth.
And of course, you can argue, well, but from the Skyrizi case, AbbVie is a power player here in immunology, but Novartis wasn't with Cosentyx, and I would also argue that UCB isn't with bimekizumab, and I think you've all seen what UCB has been able to achieve with bimekizumab in psoriasis. So again, telling you that a new offer matters, and I think you see some of you that follow know the picture here on the left. On a very, very busy market, the IL-17A/F bimekizumab still could perform the better launch, right? And if you look at the right side of this page, you see all the reasons to believe that our drug tends to even perform better than bimekizumab.
So we think that we have a real, real option here to launch a drug that presents a great benefit ratio to the market, but also ensuring you all out there, that if you do that, there is space for these markets to grow, even when they're extremely busy, like psoriasis is, which HS is not. In terms of the criteria that we think are important for access, let me just share one page with you, which I think is important as we discuss with payers. In terms of access drivers, things like disease severity, how irreversible the damage is. So what's the long-term cost of that particular patient? Are there many drugs? Is this category managed separately or together with others in a basket? What is the ceiling, and do we break the ceiling in terms of standard of care?
These are all key access drivers, and I think in this very simple picture, we hope to illustrate to you that, for example, compared with psoriasis, HS really has a lot of tailwinds, when it comes to access. Because of how severe the disease is, how much we can change the standard of care, how little competition there is versus, say, PSO, and how irreversible the damage is, so the long-term cost of the patient. The other thing that I just want to highlight here, in terms of access, is the exposure on Part D. So what you see here on the left, is a simple view of what is changing with the IRA reform, on Medicare Part D, right?
You see all the way to the left, that's what happened before the reform, especially in the catastrophic phase. Most of the cost, a little bit was handled by the patient, most of it was handled by CMS. What has happened after the reform, what we call post-reform, so the bar here in the middle, is that the expectation is that the contribution from CMS goes down as plans and pharma needs to now contribute, right? This is an important cost that is coming associated with selling an asset that has a lot of sales on Part D Medicare. This is, of course, a huge impact. You will know that a lot of the companies are looking at this very closely.
And of course, the plans will start to try to push the cost to the pharma side, but there's a huge impact here. And what is interesting is that HS, while having the same amount of commercial plans that psoriasis has, has a lot more Medicaid than it has Medicare, right? And this is very important because then the drug in HS is not exposed to the pressure that this reform creates. Is Medicaid a bad thing? We don't think so, right? As you see on the left, that's the summary from the previous page. Same commercial book of business between HS and PSO, but a lot more Medicaid than Medicare. We think that Medicare...
Medicaid is a great channel because the process is very similar to that what you do with commercial plans. So again, in terms of complexity for a small company, it would be favorable to us, and Medicare and Medicaid tends to be far less exclusionary with with MOAs, right? So we have an easier potential to compete. And for those that are less familiar and associate Medicaid with more with more discounts or worse gross to net, that's just not the case. So we think this is a great opportunity to get the market going for us and an advantage for us.
Before I leave the HS part here, i also just want you to remember that, above all, as you've seen from what we present, what we are presenting today and with what we've shown before, that sonelokimab really has a good opportunity here to differentiate from the other top competitor, which we believe to be Bimzelx. Number one, you see elevated efficacy, we're the only drug that has primary endpoint score 75. We've shown you the delta, we showed IHS4 100, which others have not. And you've seen all of this happening at week 12, so we're very confident that efficacy will be a differentiator. We also have a leading benefit-risk profile, as we've discussed before.
Let's not forget, as we've shown you before, that we have a monthly injection with very low volume, so that's another card that we can play in terms of differentiation. As Kristian mentioned, we're doing adolescent HS. We want to have this in the BLA right away on the label of the molecule. Again, the only molecule out there that has the that will have this indication. And you will be seeing this more and more in the next months, and certainly in the scientific conference circuit. Our molecule inhibits IL-17A and IL-17F, and penetrates and works in a very different way from Bimzelx, right?
So we have lots of opportunities in e market that make it possible for a smaller company like us to play, and ultimately, we have many opportunities to differentiate from the molecule that we believe will be the biggest competitor, which is bimekizumab. So just before I hand over to you, Matthias, I wanted also to share a quick view on what's happening in terms of the PsA market. I won't dwell too much on this, but there's a few reasons to believe that we can win with SLK in rheum, right? So number one, in rheumatology and PsA, the evidence strongly suggests that breaking the treatment level is key. Again, you will see that a lot of drugs have been launched over the years.
If you elevate the treatment goals, you drive the market. Yes, the landscape is more fragmented. There are more players, but we will not be competing with all players. We will be competing with the big players that are now driving the market, because we expect to be the next innovator. Obviously, you heard this from Kristian, IL-17A and F is the winning MOA. Bimekizumab show that. We show that especially when it comes to composite scores like MDA, ACR plus PASI, et cetera. We believe that there's a lot of room to grow because the current IL-17s and IL-23s that are driving the market show some limitations when it comes to PsA results. Obviously, the market is already more established.
It's already about $10 billion in size. We believe it will go to about $15 billion. But we already see here again, about 2 million patients, and growing pretty fast, about 150-175 thousand patients per year, with the share of biologics continually increasing, right? So again, I don't think there's any reason to believe that introducing an innovative drug will make us compete with every single drug out there. It will probably make us compete with the more important drugs. And also here, and again, this is one of the reasons why we choose this market, we believe that we have some very favorable characteristics as a smaller company. Again, there's a lot of concentration in this market versus, say, PSO.
Again, there are several reasons to believe that from an access perspective, we have some good advantages. In the interest of time, I will just take 2 or 3 slides here on PsA. I do wanna talk about this one. It's very important that we demystify this logic that, oh, you're launching into a market that has 20 players, right? So it's gonna be very difficult. The market has a lot of players, but we will not competing with all the players. Why? Because the way that the market developed was that we first got the molecules that impact ACR 20, a 20% improvement on the joint. Then we started introducing molecules that elevated a little bit to ACR 50. You know, and you have your, your Humiras and, and, and your Simponis, Remicades, et cetera.
Then I think there's another level of innovation, which is the drugs that really treat the skin of PsA patients extremely well, like Skyrizi or Tremfya. And then you start getting into the drugs that are truly multi-domain, the ones that have an impact, a strong impact or a better impact on the joint and on the skin. That's the IL-17A onlys that started to show good ACR 50, but also good PASI 90 response. And now, the expectation is that the IL-17A/Fs come and bring this multi-domain response. But as you see by the bubbles, everybody has a lot of sales, right? So there is a lot of potential in the market, but there's a lot of potential by bringing new drugs, so you can continue growing the pie, if you will.
As you see, the drugs that are more innovative, they tend to make more money. We will not compete with 12, 15 players. We'll probably be competing, as you can see here, against essentially four or five players, bimekizumab, Cosentyx, Taltz, and probably Skyrizi. Okay? That's important because it's not us against everybody else. Why are the molecules important? And how has the market been growing here? As you can see here, the transition from 2018 to 2024, this tells you a very important story. Indeed, the older drugs, the ACR 50-only drugs, like TNFs, strongly decreasing minus 20, and all that growth not driven by JAKs or orals, et cetera, but really driven by IL-17s and IL-23s.
Interesting to see that IL-23s grow quite a lot, despite the fact that they have very limited joint impact. A great opportunity for us to join this trend and really bring the best of both, best of both worlds. Clearly, that's where the market is going. Not again, not all the molecules in the market, but the ones that matter for us. Another thing I wanted to mention is, of course, you have to see that... You see that on the first two rows, the market itself changes, right? We used to have in 2018, about 60% of biologic-naive patients and only 40% of TNF refractory patients. As more people get treated, the market changes. This becomes a TNF refractory market, right?
And that's again, another reason to believe that introducing new drugs like Skyrizi, like Cosentyx, as you can see, has helped the market grow, especially for Skyrizi. And again, the reason why we use it in our phase III, but that, of course, there is opportunity for us to ride this wave of innovation. As you can see, the drugs are put into the market with lots of competition, and they do extremely well when they're innovating like we are. I'm gonna skip some of these markets here. I just want to... And of course, you will be having this available for consultation separately. I just want to stop here, considering the message that you heard from Kristian and from myself.
If you take a step back, as you can see here, the imperatives for us are very clear. We have to continue building the story of the HS market. It's not a winner takes all. We are here to play, and we're probably gunning for number one and the gold standard here. But it's important that we do sessions like today to continue building the market story, because it has taken a while until people understand that the market is big. Number two, the same story for PsA. We are competing with a few incumbents, and we have the potential to take them out based on clinical data, but we're not competing against twenty-five drugs here, and the future is multi-domain.
As you started hearing from Kristian, and we talked about this last time, one of the other imperatives for us is continue building that story on the new indications. You started hearing about PPP. You'll hear about other of these indications, adolescent HS, et cetera. Obviously, a big imperative for us while we're driving the market is to do everything that Kristian told you about, so that we can compete with excellence and prepare the company to win on those indications, especially in HS and in PsA. So I will stop that in terms of the tour of the market. As we move towards the end of the session, I will pass it on to you, Matthias, to take us through the next chapter.
Wonderful. Thank you, George. It's my pleasure now to walk you through the last part of the presentation. So if we move to the next page.
... You heard both Georg and Kristian talking about the potential of sonelokimab, and we are truly fascinated about the potential that we have with this asset, which also justifies our strategy to unlock the potential of sonelokimab. You've heard us talking about HS as the lead indication, PsA moving into phase III. Those two indications alone, our market research really indicates that we have peak sale opportunity north of $5 billion. And then we are adding PPP, we're adding axSpA, we're adding adolescent HS, each of these contributing potentially $1 billion or more in sales opportunity, bringing this together to $8 billion-plus in peak sale opportunity that we see. So that's why we are very excited about the asset, about the potential. We have now had over 700 patients exposed to sonelokimab. We see a very favorable benefit-risk profile. We have the mature manufacturing setup.
That is the reason why we focus on sonelokimab, and we are truly, yeah, laser-focused on the development of this asset. In terms of catalysts, here you see a summary of the upcoming most important catalyst. The machine is running in full steam at the moment. 2024 is a year of execution, is a year of setting up all these studies, initiating all these studies that you see here, all the first patient in across HS, PsA, PPP, axSpA, the adolescent HS program, the additional PsA phase II program, that we are running, that Kristian talked about. Then 2025 and 2026 will be really full of data catalysts. I mean, the most important one that we are looking at, and that probably also investors are looking at, is certainly the HS primary endpoint read as of mid of next year.
You heard us talking about it. But you also see the new indications coming in here, potentially with some interim reads even before that. You also see that the PsA readouts will not follow soon later. So truly, 2025, 2026 will be very heavy on data. 2026 will then also be the full ramp-up on the BLA submission so that we can launch in 2027 in the U.S. with sonelokimab in HS, adult and adolescent. From a financial perspective, we are in a very healthy and very, very good situation. You saw us reporting our June thirtieth cash position, so in terms of cash, cash equivalents, and short-term marketable debt securities, we ended the quarter with north of $500 million, $519.8 million. You see it here on the page.
Cash burn in that quarter is very similar to the OpEx that we experienced in the second quarter, so something approximately $30 million. Yes, that's a significant increase versus previous quarters. On the other hand, it also reflects the growth and activity. That VELA program is now running in full steam, that you see the other studies being initiated now. So it's still, I would say, if you compare it to other companies, a very still a very lean and efficient setup. You will see some increases on the OpEx side in the coming quarters, but everything fully according to plan. Most important, you see it here, the guidance in bold is that we expect to have at least 18 months of cash at hand when we read out the primary endpoint of the VELA program.
So we come from a position of strength here. Of course, we will not do this in a vacuum. I mean, today is an extensive update from us towards the capital markets. We will be present at some of the investor events that you see here on this page. We will also be very active at the scientific meetings. Kristian talked about it. Certainly, one of the highlights coming up will be EADV in Amsterdam in the end of September. Also, the HS meeting in Texas in November is a very important one. ACR, another important meeting for us. And you also see extensive coverage from now 17 analysts that cover us.
Broadly, expectations in terms of price targets, but also in terms of peak sales opportunity, are broadly aligned with the view that we have at MoonLake. Now, the final slide, some closing remarks before we open up for Q&A. I said it, 2024 is truly about execution. We are very busy. We are setting things up well for the readouts that will then start in 2025, and that will be very, very important inflection points for MoonLake. Our focus is truly on bringing sonelokimab further, bringing it to the market, unlocking the value in multiple indications beyond HS, beyond PsA. At this time being, we do not foresee any partnerships. Now is not the time to talk about this. We are focused on the development. We do not need the cash.
On the contrary, we would rather see it as a distraction right now if we were to get a partner on board for the development of sonelokimab. We continue to be the best steward to guide sonelokimab through the development, and we do now have the team in place. Since last year, our organization almost tripled in size, so now we do have the people in place, very good people to drive the development of sonelokimab going forward. And you can expect certainly for us to provide further guidance over the coming months, certainly post JPMorgan, where we will also update a little bit more on the status of the clinical trials. I think that's actually a good lead over to the Q&A.
I saw some questions coming in already, and one of the questions relates to our enrollment of the HS study. I think one question received here: How can you be three to four times faster than others in terms of speed of recruitment in HS? And also related to that, do you see a lot of competitive activity in the HS space, and how does that impact your enrollment? Maybe, Jorge, you want to answer this one.
Absolutely. And once again, from my side, thank you for all those joining the session today.
... Yes, I've heard this question, the three X to four X. I think someone has been spreading those numbers, but obviously they make no sense. I think we were very, very clear today. We shared exactly the number that we have for our recruitment rate. It is absolutely true and correct that we were about two times faster than the industry average in our phase II MIRA program, right? The 0.26 to 0.45. That's correct. But to say that we're three X, four X faster in phase III, I just don't think it's correct because as we told you, we're even assuming a slightly slower recruitment rate than we had in phase II.
So we've set an ambitious course. To go about two times faster or faster than the industry is an ambitious course, but we are an ambitious company. We've shown that we can do this before. I think the most important thing here is not the speed of recruitment, right? I think the most salient fact about the program is the fact that, as Kristian mentioned, it's a very simple design in which the placebo patients cross to the one dose arm at week 16. So that will allow us to tell a lot about the endpoints at a time where others are typically not able to do so. I think that's really the salient element. In terms of competition, yes, there is competition out there.
You have lutekizumab, you have Rinvoq, you have IRAK4, you have other stuff. It is competitive. We don't believe that it is more competitive than it was with Mira. Remember, Cosentyx was still going, bimekizumab was still going. We don't think it's more competitive. We think it's equally or a little bit less. But again, when you're competing with a drug that makes the sites so, so enthusiastic, right? That makes them immediately convert from phase II to phase III , I think we're very comfortable with our ability to compete for patients.
Thank you, Georg. One question that relates to it, and maybe Kristian, you want to answer this one. You focused a lot on assets that are coming to market soon. What about early and midstage assets like, for example, the IRAK4 inhibitor, for example, lutekizumab from AbbVie or Rinvoq? How do you see those as competitors to sonelokimab?
Yeah, I try to be brief here, Matthias. First of all, as an immunologist, chronic diseases need to have an adaptive component. That is important to understand. So I think that all drugs that focus on inhibiting innate immune mechanisms, lutekizumab, IL-1 alpha, IL-1 beta, IRAK4, I think they will ultimately be limited in efficacy, and this matches the data we have seen. I think Janus kinase inhibitors, it's interesting to see they block many cytokines that... But one cytokine pathway that does not involve Janus kinase one and two, is IL-17. So I'm not sure that a drug like upadacitinib is optimal in a disease where IL-17A/F is so dominant, leave alone the side effects, though.
If you see, you shouldn't give this drug to patients that are overweight, have a high cardiovascular risk, are smokers. I would say these are all my HS patients, so it's a little bit difficult to see. And then, a more interesting one, Matthias, that I see, tibulizumab, the Zura Bio drug, is just too early to say. Interesting MOA. I think they first go into systemic sclerosis. If I recall correctly, they start in HS, not before middle of next year, so too early to say. But right now, I see no other MOA. I really have to say that could get anywhere near sonelokimab.
Perfect. And on the Vela program on HS, what is being done to mitigate the placebo response? Kristian.
Yeah, it's a question we get again and again, right? And I'm giving the same answer again and again. You have to work hard, right? You have to do your site selection diligently. You have to train your sites superbly. You have to do your data monitoring meticulously. I think we have some training with this from our MIRA program, and we absolutely do and plan to do continue this work just like this.
Perfect. Then there is one question here on the IZAR program. You mentioned regulatory submissions for the IZAR program during H2 2024. What elements of the design of the IZAR trials remain to be defined with regulatory input? Maybe I can provide a brief update on this one. You heard us, or you actually saw a press release from us, very successful end of phase II interactions with both the FDA and the EMA. And the process, the way it works, is that you seek scientific input. You provide your synopsis of the phase III protocol, you get some comments, and then you go back. You actually revise your protocol. That's what we've done. We addressed all the comments, and that's what you saw today in the IZAR program, IZAR1, IZAR2. This is the study design already based on the input from the regulatory agencies.
Obviously, then, with the final protocol, you still need to submit to the regulatory agencies when you then start the study, and that's the process that is now going on. We're in the middle of the site selection for the IZAR program. We will then do the regulatory submissions in the U.S., in Europe, also, you saw it, Kristian presenting on it, also in South America, which will be part of the, of the IZAR program. So that's the process that's going on, but it's not that we are, waiting for any regulatory input. There are no, no areas where we would expect now the regulatory, agencies to, to still provide certain input. Then maybe one last question, which is a big one. Georg, maybe you want to take this one. Is your strategy to go alone?
Is your strategy to sell the company, or is your strategy to partner?
Yeah, and I see a lot of questions there. We probably don't have time. There's questions on obesity and design, so we hope to meet a lot of you out there in the next days and weeks to clarify all that. But on that specific question, let me take it step by step, right? About selling, as we've said before, we fully understand the incredible potential of the asset we have in our hands. And we understand the question, but we will not comment on any M&A chatter. That's one. Number two, on commercialization, I think you saw the plan, you see the plan. We've been sharing it with you. We shared more today.
We're clearly preparing the company and the market as we go, knowing that, of course, any commercial, any field push will come in 2026, 2027, right? So as of now, we are preparing to take the molecule forward. That's number two. In terms of partnerships, number three, I think that was clear. We don't foresee it in the next months. We don't need the cash. We certainly don't need the complexity. Could we entertain something in the 2026, 2027 range around the region or something like that to be debated? That's all optionality that we have. I hope that was clear and concise on those three points.
I believe so. Thank you. All right. Thank you, everyone. Thanks for joining our capital markets update today. As Jorge said, there's a couple of more questions that we received that we do not have time to answer right now, but we hope to see many of you and to discuss those questions with you in upcoming meetings, investor conferences, et cetera. As a reminder, a replay of this presentation and the presentation document itself are available on our IR website. Thank you for joining. Thanks, everyone.
Thank you.
Thank you.