This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk00: It's my pleasure to welcome here as well two of my colleagues, our CEO and co-founder, George Santos da Silva, our CSO and co-founder, Professor Christian Reich, and we are also joined here by two of the leading KOLs, Professor Ken Gordon and Professor Joseph Merola, who are joining us here to reflect on us with the data on the opportunity of simulation.
spk05: sections.
spk00: On the one hand, we will present the cirrhotic arthritis 24-weeks data. So we have a whole section dedicated to cirrhotic arthritis, one of our lead indications for sunolocumab. Then we have a whole section dedicated to the opportunity in hydrodinitis superativa, a couple of important and relevant updates also on that front. And then in the third main section, we will talk a little bit about the new frontiers for sunolocumab. Here you see the disclaimer on forward-looking statements, so please acknowledge the disclaimer. You will also have the opportunity to submit questions through the Q&A function in the webcast. Here in the room, towards the end, we will have time for a couple of questions, so then please raise your hand.
spk05: The presentation will also be available as a... Please also use the Q&A function.
spk00: Now, before we get started with the content, maybe I hand over to George to provide a little intro for those of you that are less familiar with Moonlake, less familiar with Sunilokimab. Just a very quick summary on Moonlake and on the assets Sunilokimab.
spk01: Thank you, Matthias. Good morning to all of you joining us here in the room. Good morning, good afternoon, good evening to the many of you that are joining us through our webcast. Just a couple of comments here. Moonlake is a biotech company, a clinical stage biotech company that was founded in 2021 in Switzerland on the back of a license agreement with Merck. That's the German Merck that gave us access to a very exciting new technology in biologics, the nanobody technology. But more importantly, full worldwide rights to a molecule that we're very excited about called Sonalokimab. And the reason why we're excited about this from inflammation and immunology-related diseases, and also addresses an MOA that we think is very important and new, and that is the IL-17A and IL-17F inhibition, and I'll come to a few more details on that. But we believe this molecule is a true game changer when it comes to inflammation and gives us the opportunity to treat many, many patients and obviously access a very important commercial opportunity. that we're going to be talking about today. And through those strong data rateouts, we were able to raise significant amounts of money. By now, we've raised north of $700 million. We, as I said, are a clinical-phase company. We have ran three large Phase IIb studies, obviously not very usual for a small young... As you know, we're having this session here directly from AAD. We will have Professor Brian Kirby presenting Late Breaker on that MIRA trial this afternoon in the conference. We also ran a large phase 2B called ARGO in psoriatic arthritis. We're very happy to share with you the 24-week data today. And we also built on a very robust large trial. to give a reference arm to compare ourselves to standards of care. So as we go into 24, into this new phase of the company, we really have three indications that are ready for phase three. We will talk today about HS and about PSA, and we expect the product to be in market in 2027. And in HS and PSA... Nanobodies. Nanobodies are essentially the variable region, as you see here in blue, of heavy chain-only antibodies. So here to the left of the page, you see the traditional very large monoclonal antibody. What we love about these nanobodies is that they're very small entities, as you can see here, but... We're able to bind some of these things together to create molecules that can do very interesting things. In the case of sonolocumab, which is depicted here to the right, we have two domains, and with these two epitopes, we combine two different targets, NIL-17A and NIL-17A.
spk04: is in different epitopes.
spk01: So by a third domain is all things that a monoclonal antibody cannot do. Even when we do all of these things, the molecule is 40 KD.
spk04: So it's
spk01: administration. The maintenance dose is a monthly dose. It's one ml and an injection that takes three seconds. So obviously from a patient perspective, very exciting. That's the technology which we think is very differentiating of our molecule versus any other molecule in these pathways. And as I mentioned, the pathway itself is also very... Interesting. The role of IL-17 in inflammation is well known. The inflammation by two types of cytokines, IL-17A and IL-17F. These A's and F's form dimers, as you see there with the little balls on top on the right. And it's these three dimers that signal through different conformations of receptors of IL-17. Now, what is interesting is you have molecules... The IL-17A inhibitors, they really can only inhibit the AA homodimer and to a certain extent can affect the signaling through the heterodimer of ANF.
spk04: But only our molecule, the nanobody sonar,
spk01: and another molecule called bimacizumab, a traditional large monoclonal antibody, are to bind these three dimers, the profile is very different. We combine all three dimers with very similar, very high affinity. That's very different from what bimikizumab can do. So that's the technology. That's the way that we're pursuing. And we think that the clinical data so far is nothing less than exciting. As you can see here, we're talking about HS, PSA, PSO, and other indications. Very clear... and the benefit-risk ratio. And as you can see here to the right, all our clinical data suggests that we are numerically above even bimicizumab. So when it comes to HS, as you know, we ran a very large study. Professor Ken Gordon will talk about it. We'll talk about it. This was the first ever trial to use... It is set when it comes to PSA, again, a large trial in this case, also placebo-controlled with Humira. Again, a disease where IL-17-ANF has shown to create the best responses, and we believe that we really changed the game here, especially when it comes to composite scores in PSA. Professor... plays a role and where we have an opportunity to win like we're pushing for NHS and PSA. And today we'll be telling you a little bit about what those other indications are that we're going to go for. So fantastic technology, very novel, a great MOA, already very, very robust clinical data.
spk00: Let's dive right in into cirrhotic arthritis. Clearly, everyone is excited about seeing our 24-weeks data. Maybe before we get there, Professor Merola, you can provide a little bit of an introduction to cirrhotic arthritis, the disease, what are the unmet needs, what are the challenges experiencing in this disease?
spk02: Perfect. Hello, all. I'm a senior voice. Ah. the professorial role, first of all, of the state, talking about how we're measuring it today, a little bit how we should be measuring it, and then we'll talk a little bit about unmet need, as was mentioned, including burden of disease currently among our patients and a little bit of a refresher on the data where we are currently before my colleague gets the exciting role of presenting what you're all here to hear about. So I'll dive right in. These are my disclosures. disease is incredibly important to our ability to treat the disease meaningfully in our patients. And so just to orient you for a moment, on the left-hand side of the slide here, I'll just put this here, we have really the key domains of disease. What are they? Skin disease, psoriasis, and there's sub-bullets below that, of course. Joint disease, peripheral arthritis, you see there in a more extreme variant where you have damage. Axial or spine disease, what's called an nail disease, and dactylitis, or the so-called sausage digit. You can see there a swollen digit. That's actually one of my patients from my own clinic. And then you've seen traditional measures that seek to try to understand the activity of disease using measures typically borrowed from RA, for example, such as the ACR, to look at peripheral joints, PASI, of course, for skin, and a variety of other outcome measures to look at each of those other individual domains. PainVast, looking at patient pain, very important one. And then disease severity, including overarching disease severity, such as patient globals. What I want to introduce here is the MDA to begin with. So being a multi-domain disease, the MDA is unique for two reasons. Number one, it is not just borrowed from rheumatoid arthritis, but it is... It's a very stringent and high bar of efficacy in that it really represents minimal disease activity across multiple domains. It's a high bar, and we'll talk about what those have looked like in recent studies. But a lot of our systemic therapies, we're typically looking for 25%, 30% or so achievement of MDA at primary endpoints in general.
spk05: So it's five out of seven of the domain. PASI-100, which I like very much.
spk02: ACR50 plus PASI-100 was introduced in some of our combination trials in the past where we're looking at both skin and joint impact in head-to-head studies, for example, historically, exekizumab and others. It's also a high bar. It's an important bar in that we're... And so their estimates, as you can see, are 1.5 million Americans thought to be living with PSA. We typically quote, but there are variants around this, about a third of patients with psoriasis who go on to progress to develop psoriatic arthritis. You'll see slightly lower and higher numbers around that incidence. And about 50% of... ...no psoriatic arthritis, and they feel better. They feel less achy. There's a lot of psoriatic arthritis in these patients, underscored by some of the next data. So this is the PREPARE study, very frequently quoted in our literature, that PSA is often underdiagnosed and undertreated This is just per chance. These three numbers, independent numbers, all happen to be 41%. That's just by chance. We frequently quote that 41% of patients have undiagnosed psoriatic arthritis. 40% of those who have a diagnosis of psoriatic arthritis are not on biologics. because it's new data that was presented at this meeting, in fact, among a survey of U.S. patients with psoriasis, 41% already. Fatigue has been well worked out in psoriatic arthritis. It's a key domain, as it is in rheumatoid arthritis, for example, is bidirectional with disturbed sleep. All of that plus functional impairment that patients are having presenteeism, absenteeism on metrics for work impairment. And the comorbidities we mentioned are not uncommon. A third of patients, quarter of patients with anxiety, depression, impact on physical activity, physical function. And I think, really, it makes sense here that we need to intervene not only for patients, but for broad which is, you know, you ask an academic to speak, this is what happens. You have the skin responses on the Y-axis, joint responses on the X-axis. Essentially, the take-home point at very high level is patients want to be here in the red. They want to optimize their quality of life, which means getting their skin as clear as possible, getting their joints as clear as possible across all of those domains. along with greater risk of flare, more work impairment, higher rates of comorbidities, including mental health comorbidities, worse overall quality of life. And so looking at endpoints that are composites of this, I hope I have made the case, are particularly important and relevant. I think one of our last points about unmet need is this, and this is really important. So obviously a very big unmet need at a high bar, fair, but a bar that's very, very clinically meaningful to patients. And we've hit a little bit this treatment ceiling. We've certainly hit the treatment ceiling in ACR endpoints. I think the MDA even further underscores the treatment ceiling Top line is really a nice summary of a complex topic, which is how do we best treat across the domains of disease? And where you see the green check marks, that is some of our highest efficacy by MOA in that domain.
spk05: S-M-O-A. S-M-O-A.
spk02: psoriasis, axial enthesitis, tactile nails, and inhibition of radiographic progression, which really means lack of erosion, lack of functional impairment over time with drugs that have a check mark. So let's take a little bit of a data dive now just to set the stage, and then we'll get to the exciting moment. Can we optimize IL-17 inhibition? And this comes a little bit back to the introduction that we had, the question of what is the value of IL-17 inhibition? IL-17A inhibition, for example, in a very objective, I would think, disease like psoriasis, for example. Here we have plaque psoriasis data looking at PASI-100, complete clear skin in the B-radiant trial, which was a head-to-head comparing bimikizumab, IL-17AF inhibition, to cecukinumab, IL-17A inhibition only. The data speaks for itself, showing improved statistically significant...
spk05: ANF.
spk02: And this is looking at now psoriatic arthritis. This is really impactful data from bimikizumab. Again, I think highlighting these points about the value of inhibiting both ANF and psoriatic arthritis. What do we see here? A primary endpoint of ACR50. I remind folks, if you're looking back in history, ACR20 used to be the endpoint, primary endpoint. We've shifted to ACR50. essentially, bimikizumab in this case behaving as well as our gold standard and best-to-date treatment in psoriatic arthritis, which was adalimumab. But we see a consistent message of much higher skin efficacy across other domains, much higher efficacy across other domains, including skin, as shown here with the PASI-90 data, where there's a clearly improved benefit here of skin
spk03: the mda data and then what we see here again is now looking at a snapshot across the entirety of
spk02: psoriatic arthritis domains, 45% of the MDA data. And what we see here again is now looking at a snapshot across the entirety of psoriatic arthritis domains, 45% achieving minimal disease activity. That's a fairly high percentage.
Disclaimer