Good evening, and welcome to the Alumis Virtual KOL Event. At this time, all attendees are in listen-only mode. A question- and- answer session will follow the formal presentations. As a reminder, this call is being recorded, and a replay will be made available on the Alumis website following the conclusion of the event. I'd now like to turn the call over to John Schroer, Chief Financial Officer at Alumis. Please go ahead, John. Thank you. Good evening, and thank you for joining us today. Before we begin our formal comments, let me remind you that during today's webcast, we will be making forward-looking statements that represent the company's intentions, expectations, or beliefs concerning future events. These statements represent our views as of this date, are subject to risks and uncertainties and should not be relied upon as representing our views as of any subsequent date in the future. We're happy to be here in Denver at the American Academy of Dermatology Congress, and to have with us here today, Dr. Andrew Blauvelt, who is a leading dermatologist and expert in psoriasis. Also with me on the call are Martin Babler, our President and Chief Executive Officer, and Dr. Jörn Drappa, our Chief Medical Officer. Looking at our agenda, Martin will begin by providing an overview of envudeucitinib, our next-generation TYK2 candidate, and the importance of TYK2 inhibition in psoriasis. Dr. Blauvelt will then walk through the phase III data that he presented yesterday to the medical community during the late-breaker research session at AAD. Next, Jörn will provide some context related to the evolving treatment landscape. After which, Martin will review upcoming milestones for envudeucitinib and the future opportunity for this program before wrapping up the prepared remarks. We'll take questions. We appreciate you joining us on a Sunday evening. We plan to wrap up our prepared remarks in approximately 30 minutes. I would like now to turn the call over to Martin. Thank you, John, and thank you all for joining us this evening. We are very excited to show you the exceptional envudeucitinib data and share a bit of perspective from AAD over the last few days. We have had the opportunity to connect with many members of the medical community, and at the conference, there is strong enthusiasm for envudeucitinib based on the totality of the phase III data that we shared, including yesterday's additional results in the late-breaking session. Envudeucitinib has shown consistent performance across trials and endpoints with speed of onset, leading PASI skin clearance and patient-reported outcomes, all of which we know are critical drivers to keeping patients on treatment to achieve durable disease control. Here's why that matters. As high-efficacy orals enter the treatment landscape, we expect the category to grow significantly, and patients need choice, and the psoriasis market has a track record that shows that there's room for multiple successful treatment options. I would like to go to the next slide now and really talk about how we believe that envudeucitinib will be a leading treatment of choice, delivering leading PASI 100 skin clearance and compelling differentiation on symptom relief, a true new dawn for TYK2 inhibition. Our data are consistent, comprehensive, and confirmatory. First, with respect to skin clearance, envudeucitinib demonstrated leading and consistent performance across trials in the ONWARD trials. Envudeucitinib-treated patients achieved robust skin clearance with early onset of action and responses that continued to improve out to week 24, with no plateau observed. This includes high-impact areas like scalp psoriasis. Second, key data that we shared at AAD shows comprehensive benefit across patient-reported outcomes, the key measures that patients care about. Patients experienced quality of life and itch improvements. Most notably, those improvements appeared even before the early PASI 90 skin clearance responses. Importantly, envudeucitinib has achieved all of these endpoints while also demonstrating a favorable safety and tolerability profile. Third, we believe these highly positive data are confirmatory of the importance of maximally inhibiting TYK2, a central upstream regulator of multiple disease-driving pathways, which block both IL-17 and IL-23 to address immune dysfunction. Next slide, please. TYK2 has been validated as a target in several immune-mediated diseases, but it hasn't reached its full potential until now with envudeucitinib because the other molecules have not been able to maximally inhibit TYK2. Our theme at AAD reveals a new dawn for TYK2, resetting expectations for what a next-generation oral drug can achieve for patients with psoriasis. Envudeucitinib was intentionally designed to deliver 24-hour maximal inhibition of TYK2 with high selectivity. We believe this translates not only into high level of skin clearance and favorable safety profile that we've seen across our clinical program to date, but also the meaningful improvement in quality of life and symptom measure. To control and combat systemic diseases like psoriasis, patients need effective systemic therapies. We believe that's the power of blocking IL-23 and IL-17 both with inhibition of TYK2, an oral treatment that could deliver fast relief with both skin clearance and quality of life and could be taken over the long term. With that, I would like to introduce and turn the call over to Dr. Andy Blauvelt. We are pleased to have Dr. Blauvelt join us, a leading dermatologist and immunologist with decades of experience spanning both academic research and clinical development, and deep expertise in psoriasis. He trained at the University of Miami and the NIH, and has held senior roles at leading institutions, including the NIH, OHSU, and the Portland VA. He most recently led Oregon Medical Research Center, where he was the lead and senior investigator for many important clinical trials in this space. Dr. Blauvelt is internationally recognized for his work in psoriasis, including pioneering contributions to the IL-23/Th17 biology and has authored more than 450 publications. He continues to play a role in global clinical trials, advising companies including Alumis, and currently serves as the chair of the medical board for the National Psoriasis Foundation. With that, please, Dr. Blauvelt. Thank you, Martin. I appreciate that introduction. Very kind words. Thank you. Thank you to the investors for taking the time today. I'm excited to share with you the results of envudeucitinib phase III studies. This is always a big event in the field of psoriasis, actually in the field of medicine, when we see for the very first time phase III results. Lots of excitement over this, lots of time and effort, many years in the making, and yesterday we had the reveal. Today, one day later, I'm gonna share that reveal with you, and I'm gonna highlight really the details from the phase III study, so you all have a good understanding of where this drug sits in terms of its efficacy, safety, and convenience. As mentioned, I've been an advisor. Next slide. I've been an advisor for Alumis, and I actually have been an investigator with envudeucitinib in the phase II program. I do have personal experience with the drug itself, as well as many other psoriasis drugs. Next slide. Okay. The mechanism. TYK2. What is TYK2? TYK2 is a JAK kinase, but it's not like the other JAK kinases. There are four JAK kinases, JAK 1, 2, 3, and TYK2. TYK2 is much more selective in terms of the cytokines that it controls the signaling for. What's shown here is three particular types of cytokines, IL-12, IL-23, and type I interferons, which is interferon alpha and interferon beta. We know that when a cytokine binds to a cytokine receptor, shown in the middle, that there's a signaling process, so we call this signal transduction, and just downstream of the cytokine receptor is the TYK2 molecule. We're inhibiting intracellularly here, inside the cell with a small molecule binding to TYK2. Now, what's also shown here on the left is that it's binding in a region that is not the catalytic region. The catalytic region of the kinase where ATP binds is nonspecific, if you will, for TYK2, whereas the regulatory domain shown on the left side, the more pinkish lobule here, that is the regulatory domain of TYK2. That is where envudeucitinib binds. It's an allosteric inhibitor. Which means that it changes the shape of TYK2 and prevents binding of ATP. It doesn't bind in the ATP site because that would be too nonspecific. We might get overlap with other JAKs. We get a specific binding in the regulatory domain. It changes the shape and that's how it inhibits the activity of this enzyme. When we block there, we do not get signaling of those cytokines that I mentioned, IL-12, IL-23, and interferons. Now, there's one other TYK2 inhibitor, deucravacitinib. Many of you know it. It's known as also Sotyktu on the market. We know that this is a proven target in psoriasis, but there's been a number of problems with deucravacitinib in the past. The makers of envudeucitinib, Alumis, have tried to address every single problem that had occurred with deucravacitinib, much of it going into the design of the molecule. We call it a next generation or second-generation TYK2 inhibitor. It was specifically designed to give maximal inhibition of this target, TYK2, over an entire 24-hour period of a day. Complete and maximal inhibition of this particular enzyme, TYK2, continuing without any lapses in the coverage, if you will, of this inhibition. Now, we did have the phase II results. I actually was involved in the phase II study, as I mentioned, and we knew that this drug worked, but we needed to test it, of course, in a phase III study, larger population, with control groups and so forth. That's the background. Next slide. The designs of the two studies were identical. ONWARD1 and ONWARD2 were the names. They had an envudeucitinib group, a placebo group, and an apremilast group. Patients were randomized 2- to- 1- to- 1 to these three groups. Standard dose of envudeucitinib that we had identified as the best dose in phase II was 40 mg twice daily. The active comparator here is apremilast or Otezla, a leading oral drug for psoriasis. 30 mg BID, standard dosing. Then of course, the placebo group. The primary endpoint was week 16, standard time point, and the primary endpoint was a co-primary endpoint of PASI 75 and sPGA 0/1, which means clear or almost clear skin. Standard endpoints, and pretty much standard inclusion and exclusion criteria as well. Moderate to severe plaque psoriasis, 10% or more body surface area. Basically, you can see the things here on the slide, but just suffice it to say, a typical inclusion and exclusion criteria matching essentially the other systemic therapies for psoriasis. Now, we did also have a number of secondary endpoints, and I'm gonna go over those each as we see the data later. I'm not gonna list them now. Next slide. Oh, and I wanted to point out that even though the primary endpoint is at week 16, I'm going to be showing week 24 data. Why do that? Why is week 24 data even being shown if it's all about the primary endpoint? Week 24 is actually important for any drug that blocks IL-23 because we know IL-23 blockers in general, whether it's an oral drug, a biologic drug, or this drug, a TYK2 inhibitor, we know that the efficacy continues to rise with IL-23 blockers over the course of the first six months. Indeed, that's what I'm going to show you, is that we see improvements from week 16 to week 24 consistent with its inhibition of IL-23. All right, we now have the baseline demographics and disease characteristics. This slide is actually important for a couple of reasons. Next slide, I'm gonna talk about some highlights. There's gonna be some box things here. Yeah. First of all, the age. We had a fairly significant number of patients over the age of 65. We actually think that's important. We need to establish both efficacy and safety in that group. We didn't shy away. Around 10% of patients were over 65. We didn't shy away from them in this study. We have a good number of patients who are over 65. Predominantly white patients, that's consistent with other psoriasis studies, and it's gonna come up again if we talk about the competitor of this drug, which is zasocitinib. Duration of disease, PASI, sPGA. This was a robust population in terms of their disease severity. Pretty severe. When we look at the PGA, what that means is a global score of moderate or severe, three or four. About 70% of the patients were moderate, about 30% were severe. Again, the competitor trials, you should be looking at these demographics. We would suggest our population was a little bit tougher in terms of the demographics compared to zasocitinib's demographics. Prior systemic treatment, about half of the patients had received systemic treatment prior. This means that it was a tough crowd. It's a solid, patients with solid disease. We're not talking about mild patients here. One more thing, the pruritus score. So pruritus means itch, zero to 10, with a 10 being the worst possible itch that you could ever have. On average, we had about a score of six out of 10, and I'm going to be showing you some data later. Remember that baseline average of six, because when I show you the itch data, it's to me quite impressive. Next slide. All right, so here is the first co-primary endpoint data, week 16, and it is the PASI 75 rate in blue is the envudeucitinib data in the far left of each of these graphs. We have ONWARD 1 on one side. We have ONWARD 2, the second study, on the other side. As an investigator with lots of experience in doing these studies for so many years, I always try to see if the studies are balanced. When they are, when they're similar data, that's a good thing. When the data is too far removed, I always wonder what happened in one study versus another study. To me, these numbers are comparable, 76.5% versus 70.4%, in terms of the number of people who had 75% or more improvement. Then if we look at higher levels of improvement, that's called PASI 90, and then complete clearance of skin is PASI 100. We see here, if we just focus on the PASI 100, numbers that are 27.7% in one study and 29.4% in the other study. Close to 30% of patients achieving 100% clearance four months after starting drug. If we look at the apremilast rates here in orange, we see it's markedly better than apremilast. No surprise there. The placebo rates were low in this study, in my view, especially when we look at the higher levels of clearance, the PASI 90, the PASI 100. Next slide. Now, here is what we're adding here is the week 24 data. Same measures, PASI 75, PASI 90, PASI 100, but now we're looking at week 24. As promised, things go up. Again, not as promised, but as expected, I should say. As expected, things go up from week 16 to week 24. Because of the mechanism of action, because it works by blocking IL-23 as one of its main cytokines, we know that those drugs take a little bit longer, and we see things going up. Particularly I like to see, and I highlighted it here in green, the PASI 100 rate of complete skin clearance. Now we're up to 39.5% in one study and 41%. 40%, essentially, of patients achieving 100% skin clearance. This is the ideal result. This is the result that patients want. They want to be completely clear. Again, this is gonna be discussed later, but to me, just suffice it to say these are very impressive numbers to have a drug with 40% PASI 100 at week 24. Next slide. Okay, now we're actually showing the PASI 90 rate, which is a significant amount of clearance. These patients can be thought of as clear or almost clear, and that's so how you should think about PASI 90. What we see is that patients start to achieve this very high endpoint as early as week four, and they progressively get better again over the course of week 20, 24 weeks, getting up to about 65%, or 2/3 in that range, achieving this very high level of clear or almost clear. In this case, it specifically is PASI 90, but essentially means clear or almost clear skin. 2/3 of patients reaching this. Next slide. Of course, the apremilast rates are all they're much lower, so I'm not even gonna highlight the apremilast rates. Here we're looking at the PASI 100 or complete skin clearance rates over time, and it's little bit different actually than what I've just shown you, because we do not see a plateau of this important endpoint, this ideal endpoint of patients, what patients want. They want zero disease. They don't want even a single lesion. This is really what they want. We see it continually going up through week 24, but we also do not see a plateau. Maybe it would plateau after week 24, maybe not. We don't know right now given this data, but it certainly is exciting and kind of enticing, I guess is a better word, to see where this can go. Do patients continually have a PASI 100 response? Is this going to be higher or is it going to plateau? No one knows for sure, but it's exciting to think about it given what you're looking at right now. Next slide. All right. This is the other endpoint, the other co-primary endpoint, which is called sPGA 0/1. GA means Physician's Global Assessment, and zero one means clear or almost clear. We see numbers that are consistent with those PASI 90 numbers that I mentioned. I mentioned clear, almost clear officially tends to correlate very closely with PASI 90, and that's what we see here. Patients are getting up in that 2/3 of patients achieving this clear or almost clear. I also didn't specifically mention, I should have, but everything is statistically significant. There's statistical significance versus placebo, versus apremilast at the primary endpoint and throughout many of the other endpoints that you're seeing, time points that you're seeing. Next slide. I love these pictures. A picture's worth a thousand words, right? This is a real person. So you can show numbers all day, but this is severe psoriasis on the left. The lesions are thick. They're deeply red, deeply inflamed. It's a horrible disease. It really is. It has a significant impact in people's lives. You can see after just two weeks of envudeucitinib significant improvement actually in the upper right of the severe lesion, and then it's clear at week eight. What we see there at week eight and week 16 is what we call post-inflammatory hyperpigmentation, and that doesn't count as psoriasis. That is not active psoriasis. That's residual pigment seen after inflamed skin is healed. We're showing clearance of this very severe lesion basically by week eight. Very exciting picture. Next slide. I like this one as well because here the scale is very thick, very white, silvery scale. This is what psoriasis looks like when it's untreated, and it sits there for a long time. I showed you a lesion that was very inflamed, very red, and now I'm showing you one that's very thick and scaly. These lesions were probably been sitting there for years, and I'm not making that up. This is what psoriasis looks like after years of sitting around untreated. It gets that very, very thick crust and very, very thick scale. Look at week two. We already see the lesion start to break up, a lesion that has likely been there for years. Again, like the last patient, by week eight, it's essentially clear, and it's completely clear, again, after having it for many years, which I'm sure of because I know what lesions look like when they've been around a long time. This is drama. This is a great result. Next slide. This may even be the best one yet. This one shows not only an incredibly inflamed lesion, so red, deep red, but extensive, covering the entire lower back and buttock. An extensive inflamed lesion. This patient, unfortunately, was on placebo, and we see at week 16 essentially no change in the lesion. Eight weeks after crossing over to envudeucitinib, because they went into the open label, that was the design of the study, placebo patients went over to active drug, he's clear. He's clear over this entire back and buttock, very dramatic, after enduring that placebo control period. Next slide. All right. What about what we call high impact sites? High impact sites, or HIS, is an abbreviation we use for when psoriasis involves the scalp, the palms and soles, the genital area, or the nails. Why do we call them high impact site? Because we have quality-of-life studies, showing that when patients have disease in those areas, there's a disproportionate effect on their quality of life. They have horrible quality of life if they have a HIS area involved. Here we're actually picking out data from scalp psoriasis. This is the percentage, what I'm showing you, of those patients, that subset of patients with moderate or severe scalp disease, who go to clear or almost clear on their scalp. We see about 75% of patients with this very tough-to-treat area, this highly impactful area, are clear or almost clear after 24 weeks of therapy. This is always good data to have. Another thing about scalp, it is the most common area of involvement in the body of psoriasis. About 80% of patients with psoriasis will have scalp involvement. This is very relevant data to show this subset analysis that it does particularly well in patients with disease in this area. Next slide. Okay, now we're gonna switch a little bit to the quality of life and the patient-reported outcomes. What I'm showing here is itch. Now, again, how do we measure this? I'm gonna briefly say it. We tell the patients to record the number of their itch from zero to 10, with 10 being the worst possible itch they've ever imagined in their life. We keep asking them that question during the trial. Again, the average itch for patients entering in ONWARD1 and ONWARD2 was six. An average six out of 10. What we're showing here are average drops from six downward, and we see it going over the course of 24 weeks in the two studies, dropping anywhere from 4.3 to five points. If you start at six, and you're dropping by 4.3, you're getting down to an average of 1.7 in the one study. In the second study, you're getting down to an average itch score of one. One out of 10. This is dramatic drops in itch, is what I'm trying to say. Trying to interpret the slide for you, but this is dramatic drops in itch, and this starts as early as two weeks. Look at the early onset here. The drug in blue here is having a significant effect on itch as early as two weeks, and we see it continuing out over the course of 24 weeks. Apremilast in orange, again, placebo in gray. Next slide. One of the things we always measure is quality of life, and we use a measurement called the DLQI, the Dermatology Life Quality Index. It is a standard measurement. When patients have scores above 10, it's a big impact in their quality of life. We had an average starting point of around 10 in this trial. This, what we're showing here, is the percentage of people that go to a score of zero or one, and this is considered a very high bar. To start at a 10 effect on your quality of life, if you can go to zero, that means the disease has no effect on your quality of life. If you're at a one, that also actually means no effect on quality of life. A score of zero or one means no effect on quality of life. Look at the numbers. We're above 60% where the psoriasis now has no effect on their quality of life after 24 weeks of therapy. Again, people who've had disease for a long period of time, with a horrible effect on their quality of life. 2/3 of them, 60%, whatever, in that range, having no effect with this treatment over the course of 24 weeks. Pretty dramatic results. Next slide. Now, this one we tried to overlap what I just showed you earlier, and what we're trying to show here is as the itch drops, and that's in the light blue, which happens in the first two weeks. We also see the quality-of-life score start to improve. The significant skin clearance, what we call PASI 90, tends to lag. What we're trying to show is that before we see significant skin clearance of PASI 90, where it's a high bar of skin clearance, before patients can get there, they're having improvements in their life, in their itch and their life in that first month of therapy. A pretty interesting result. Next slide. Okay. There's another measurement. We call it a patient-reported outcome. This is called the PSSD, Psoriasis Signs And Symptoms. We ask the patient about itch, we ask them about skin pain. We ask them actually a series of questions. If they score high, that's bad. If they score zero, it means they're not having signs and symptoms of psoriasis. We went to the high bar. What we're showing here is people who score zero on this survey of how the psoriasis is affecting them, and we see over a third of the patients on envudeucitinib go to zero in terms of the signs and symptoms of their disease. Again, asked by us and answered by the patient. Another key sort of important patient-reported outcome of success. Next slide. Safety. That's the efficacy. You can tell I'm excited by it. The safety I'm excited by too. Here is the week 16 safety. We have envudeucitinib in one column, we have placebo, and then we have apremilast. And we look, let's look at the most frequent, adverse events here. Nasopharyngitis was the most frequent, actually headache was the most frequent, side effect for envudeucitinib. It was 10%, 2.5% in placebo, 9.1% in apremilast with headache. So kind of comparable there to the control groups, but more than the placebo. Upper respiratory tract infection, you can see the numbers, 4.8% versus 3.7% with the other active drug, 1.6% with the placebo. What else? Nasopharyngitis, 7.2% versus 4.8%, 3.7%. A little bit of minor things here. Most of these are mild to moderate, not severe, and not leading to drug discontinuation. Those are good things always to talk about with AEs. Are they severe? Do they lead to people stopping the drug? We didn't see much there. The other things we saw in the apremilast groups that we expected, shown here is nausea and diarrhea. As expected, we see more of that with apremilast, which are known side effects. We don't really see that with envudeucitinib on those GI tolerability issues. The next slide. We go to a little bit longer. This is a little bit longer safety. It's adding on an additional eight weeks, and essentially the numbers are not changed. We don't pick up any more AEs, if you will, with a little bit more time. We do have, you know, safety data with this drug out through one year in the phase II study, but obviously, this is a bigger study. The other important thing kind of noted below here, no blood test abnormalities, nothing in the blood count, nothing in the serum chemistries, no deaths. There's a number of no things. No deaths, no MACE signal. There was one MACE case, but no MACE signal essentially. The rate is consistent with the background rate. No TB reactivation, low serious infections, low malignancies. This is what we'd like to see in a safety slide for a systemic treatment for psoriasis. Next slide. In summary, envudeucitinib, a next generation or second generation TYK2 inhibitor, delivered early and progressively deepening skin clearance with meaningful improvements in patient-reported outcomes, and I showed you a number of those. The progressive is really the data from week 16 to week 24. We do think this drug has the potential to go even farther in terms of the responses beyond week 24, but that has to be proven. We had everything meet successful endpoints in terms of statistical significance, with approximately 65% of the patients who are clear or almost clear, and about 40% of patients completely clear that ideal goal. Those were the week 24 data. Significant improvements in quality of life and itch, kind of talked about that. The safety was really no new signals over and above what we had seen over the years with Sotyktu and essentially nothing I think to really worry about. Obviously, we need longer data. That's very important in any psoriasis drug. We need long-term data, but that's ongoing, right? We'll have that data. Lastly, it right now is a twice-a-day drug. There are plans in place for a once-a-day formulation, perhaps Martin can talk more about that, and plans to test the drug in patients less than 18 years old in children, adolescents, and even younger ages. To be competitive in psoriasis, it's always good to have a drug over the course of different ages, but it is typical to have drugs approved first in adults and then move into the pediatric space. With that, I think that's the last slide. Let me see. Is there one more? Next slide. Okay. Yeah. Perspectives on unmet need in treating psoriasis. We do believe there's study after study to say that patients are still untreated. There's still many untreated patients out there despite all the drugs we have. There are still undertreated patients. What do I mean by that? It means a moderate to severe patient being treated with topical therapy or being treated with a light box or methotrexate. Those are 20th century treatments for psoriasis, and we still have many people stuck in the past and not using modern biologic therapy or modern oral therapy. They're stuck in the past. We know through surveys that there's still a large number of people who are either untreated or under treatment. We also know that patients tend to cycle through therapies. They go from one to another. They get bored. It stops working. They get a side effect. There's, I think, always a need for great new drugs in psoriasis, even though we already have a lot. Oral drugs in particular, we need more oral drugs because the landscape has been dominated by biologics. Many people don't wanna take shots. Many dermatologists, actually, I think it's unfortunate, don't like to prescribe biologics. It's too much hassle for them, so and they like pills. But we haven't had great pills up until now. Having great pills is definitely a, I think, a great thing for patients and will be a great thing for many dermatologists who just prefer that route over injectables. There's also a move to try to treat patients earlier. There's emerging data now that treating psoriasis earlier, you have more likelihood of success, if you do that. There's movement there, lots of room for growth in treating patients earlier in their disease. With that, I think I will stop. Thank you. All right. Thank you, Dr. Blauvelt, for this detailed review of the phase III ONWARD results. As Martin said, we were really excited to share this data at AAD and discuss the data set with many clinicians and experts in the field. I think there are three or four things that particularly resonated, and I think Andy has covered most of them. The first of all, of course, there was the deep and sustained skin clearance responses across both PASI 90 and PASI 100. Sort of the optimal outcome for patient complete skin clearance, and we achieved really high rates there. Secondly, the significant improvements in measures of quality of life and robust symptom relief. I think that is important, not only to patients, but I think increasingly recognized by many physicians as well, that is critical to our patients' well-being. Of note, we saw early onset of action. A lot of the improvements in quality of life and symptom relief occurred very early, as soon as two weeks after treatment. In many patients, even high degrees of skin clearance, including PASI 90 and PASI 100, were observed early. All of this went along with a really very benign safety profile with very few serious adverse events, very few discontinuations as a result of adverse events, and really no concerning signals relating to lab abnormalities, malignancies, and serious infections. I think all of these key points underscore the potential and promise of envudeucitinib as a leading oral treatment option for patients with moderate to severe plaque psoriasis. I'd now like to highlight some of the key areas where I think envudeucitinib shows really compelling differentiation in the context of other datasets that have been reported. Next slide, please. First of all, I think it's really important to highlight the consistency of our data. As Andy alluded to, we use two different measures that both represent complete skin clearance. One is the PASI 100, and the other is the sPGA 0. Both of these should normally march in lockstep. It was very reassuring to us that we did indeed observe that the rates in between the PASI 100 and the sPGA 0 marched in lockstep and were basically identical. Really the same was true for the clear or almost clear skin, which is measured by either PASI 90 or the sPGA 0/1. They also marched in lockstep. That, in my view, is sort of almost like an internal quality and consistency check that I think we passed. Next, let me highlight how this data compares, in the next slide, to some of the other datasets that have been reported for recent oral drug candidates for moderate to severe plaque psoriasis. I wanna precede this by saying that, you know, across trial comparisons always are dangerous. We still do them all the time, but we should only do them when studies are designed in a very similar way and when they enroll very similar populations. It is really important to understand that even subtle differences in trial populations, including factors such as, you know, baseline disease severity, duration of disease, ethnicity, geography, all of these can play an important role in creating variability. I think as you see here, we had very little variability, even though this was a global trial. In some of the other datasets, there's considerably more variability, where you have as much as a 10-point or over 10-point delta between replicate trials. I think that's an important thing to understand. Let's next look at the broader profile beyond skin clearance that Andy has already shown. This slide. I think in the past, people have really been laser-like focused on skin clearance only. I think people come to the realization increasingly that how patients feel and what their quality of life is important when it comes to what drug they choose to use and what drug they choose to remain on. I think the magnitude of itch reduction Andy has emphasized is pretty much unprecedented and is actually of a magnitude that in trials in atopic dermatitis has been sufficient to be included in the label. The FDA typically sets a threshold of on average 4-point improvement, and we have met or exceeded that in both trials. As you can see, the reduction in itch really is mirrored by a rapid improvement in the quality of life. A little bit later you see the higher levels of skin clearance. In summary, I think we believe that ESK-001 has a really highly compelling profile. It has demonstrated a combination of biologic-like skin clearance with a favorable safety profile across both phase III trials. Importantly, it was well-tolerated with a low rate of serious adverse events and discontinuations and no signals related to serious infections, malignancies, and cardiovascular events, nor any signals relating to lab abnormalities. This is clearly not the end of the story. There's additional data coming. Our long-term extension trial is in progress. We will have data on the durability and maintenance as well as longer-term efficacy, and safety and tolerability data coming in the second half of this year. There will be additional sub-analyses relating to palmoplantar disease and nail psoriasis, and there will be a pretty comprehensive effort to analyze biomarkers and see whether any particular biomarkers relate to clinical outcomes. I will stop here and turn it back to Martin. Okay. Thank you, Jörn, and thank you, Dr. Blauvelt, for sharing the data with us. This was a huge milestone for us as a company to share this data with the phase III. It's also a new beginning for the company as well because as we embark now on looking to basically take advantage of TYK2, not just for psoriasis, but across other indications. The most important thing for us is we have, with this data now, really shown that when we met all the primary and secondary endpoints and showed this very compelling data set, that we know now that TYK2 is really affecting, and especially ESK-001 is affecting, the IL-23 and IL-17 pathway quite considerably, which really allows us to go broader. As Jörn just said, later in the day, in the year, we will show additional data and also anticipate filing an IND, sorry, an NDA for this, indication with the FDA. At the same time, as most of you know, we have an ongoing program in lupus. We're really with the intention to, figure out how TYK2 works on the interferon pathway and what we can do for lupus patients. We read this, study out. Actually, it's a phase II-B that was designed as a pivotal study. We'll read that out in the third quarter of this year. That will not just basically help us understand lupus and how TYK2 and specifically ESK-001 does in lupus patients, but will also open up multiple other interferon-driven diseases. This is our second proof point, if you so want, on the mechanism of TYK2, and we're really looking forward to that data set as well later in the year. If you go to the next slide, please. Of course, one of the things we have now learned from our efforts, not just with ESK-001 in psoriasis, but also with our genomic work that we did and other efforts that went on, is that there is a huge opportunity here. As a company, we have really the advantage to have two pipeline-in-a-pill opportunities with ESK-001, but then also with A-005. We've shared with all of you that our intention now is to look at additional indications that we'll pursue. We'll announce our plans for additional indications in the second quarter. You can see here certainly that with the IL-23 side of things and then with the interferon alpha axis, we have a significant opportunity not just across dermatology, but also across rheumatology, gastroenterology, neurology, and then other indications. We very much look forward to continuing our work with ESK-001. Before we conclude, I would like to thank all the investigators, all the patients, and especially also the Alumis team for achieving this significant milestone as a company. We just recently celebrated our five-year anniversary as a company, and having a complete set of phase III data that looks like this within five years of starting the company, we believe has actually only been able to accomplish with a team that has just done countless and really huge efforts. I wanna thank the team for everything that the team has done. With that, I would like to take questions. We'd like to turn it over to the operator. Great. Thank you, Martin. Yes, at this time, we will be conducting a question- and- answer session with our speakers. Please hold for a brief moment while we poll for questions. Our first question comes from Eric Schmidt at Cantor Fitzgerald. Please go ahead, Eric. Well, thank you, and congrats on a couple of really clean data sets. Question is around the potential need for TB testing. We saw that icotrokinra's label does not require such testing. I'm wondering if the company has a view on what it might need in order to get a similarly clean label. I think Dr. Blauvelt also has published on this topic, so we'd love to hear his views on the mechanism. Thanks. Okay. Maybe, Jörn, do you want us to first start with the company's perspective, and then, Dr. Blauvelt can talk a little bit more about the mechanistic side as well? Sure. I think we now have an accumulating data set supporting the notion that inhibiting TYK2 really does not pose a very significant risk of TB reactivation. We have not seen this in our trial, despite having had about 39 patients or so with a history of latent TB. In the case of zasocitinib, what they've reported yesterday is they also did not see any cases of reactivation. We believe that while you could certainly postulate a theoretical risk, that the real-life risk appears to be very low. With all of this data in hand, I think we have a pretty solid case to make to the agency that we should not require TB testing in all patients. But ultimately, the decision is obviously up to the regulator. Andy, please add. Yeah, I think you summarized it well. I think theoretically you could expect reactivation of TB because of the blockade of IL-12, which drives TH1 responses and is usually involved in granuloma formation. It's that piece of the TYK2 inhibition that's potentially problematic, or at least from a theoretical point of view. Then the data is the data. I think the case for the FDA would be if we had latent TB patients in the trial and there's no reactivation, that's a good thing. That's if that's the starting point, if we come with that data, that's the best we can do, right? The best we can do is no activation, and then will they use that data, or will they be cautious and say, "Well, theoretically, it could," and still require it. Who knows what they'll say? There's more of a cleaner case for selective IL-23s not doing TB testing than there is for TYK2 inhibitors. Thank you very much. Thanks for the question, Eric. Our next question comes from Chris Yu at Morgan Stanley. Please go ahead, Chris. Hi, this is Chris on for Terence. Thank you for taking our question. Just kind of curious on your latest perspective for a partnership for envudeucitinib based on this positive data. Thank you. Yeah, Chris, thank you for the question. I think the question we really need to reframe a little bit, because I think it's not about envudeucitinib in psoriasis only. I just showed you a slide that shows you about 20 different indications that we can go after. If you think about we have two molecules, we have about 20 indications. We have one molecule that has now really shown that it's very safe and quite effective. Thinking about basically how we would do that on a global level, I think the likelihood that we would develop a molecule like that or possibly two molecules like this on a global level by ourselves across multiple indications is very unlikely. Our plan remains to actually look at can we find a partnership that is really the right partnership for us as a company, and how do we best move forward? I think us going into psoriasis and multiple other indications by ourselves is not a very likely outcome here. Great. Thanks for the question, Chris. Our next question comes from Thomas Smith at Leerink. Please go ahead, Thomas. Hey, guys. Congrats on the stellar data, and thanks for taking our questions. Actually, I would love to get the company and Dr. Blauvelt's view on this. Based on the clean safety profile to date, how are you thinking about the potential for a differentiated label versus Sotyktu with respect to broader safety and monitoring requirements beyond just the TB testing? And then, maybe as a follow-up for Dr. Blauvelt, with respect to the PASI 100 curves and the lack of plateau, where do you think this drug with its target coverage could land with longer-term treatment? And do you think it could be differentiated relative to zasocitinib and icotrokinra? Thanks so much. Okay. Dr. Blauvelt. Let me start by addressing. Yeah. Oh, okay. Go ahead. Go ahead, please. Yeah. Let me address the first question on monitoring. Based on the data, we have collected across over 1,800 patients, we have really not seen any evidence of lab abnormalities of clinical importance. Of course, in any study, there will always be the occasional lab excursion that returns back to normal at the next test. There were really no trends of concern. There was no systematic trend towards, for example, lipid abnormalities, liver function test abnormalities, anything related to cell counts or kidney function, none of this. I think this is, in my view, a pretty compelling data set to present to the agency, and to support our notion that there really should not be any lab monitoring be required. As in the previous discussion, of course, the final call is with the agency and, you know, how much importance they place on actual data versus their conservative and cautious posturing. Yeah, I'd say the newer generation TYK2s have a case here. They have a case for not taking the same Sotyktu label and copy and paste it on the new ones. I mean, it should be a data-driven decision in my view. If there are no triglyceride elevations with this drug, it shouldn't be copied and paste from Sotyktu about triglyceride. It's just, it doesn't make any sense to me. It's gonna be driven by the data. If it looks completely clean, there's a great case, in my view, for not copying paste, not making a class, but to make it specific, modifying that Sotyktu to fit the data of envudeucitinib. In terms of PASI 100 question, it is true that psoriasis experts like myself will look at where each drug maxes out in terms of PASI 100. We all know that we go beyond the week 16 endpoint where we lose the placebo control, and we know that it's more open label beyond week 16, but we still do it. We all know the numbers I'm gonna state now. BIMZELX, bimekizumab plateaus around 70% PASI 100. SKYRIZI and Taltz plateau around 60% PASI 100, and TREMFYA plateaus around 50%-55% PASI 100. We are at PASI 100 at week 24 of 40. Where can it go? I suspect it could go to the mid-50s%, which will be consistent with about, you know, 50%, mid-50% - 60% would be the best IL-23 inhibitors. If we truly are shutting down IL-23 highly effectively, that to me would be the maximum that envudeucitinib could get to, is 55%-60% PASI 100. Who knows? It may not be more than 50%. But still, 40% is a considerable number at week 24. Super helpful. Thanks for the color, and congrats again, guys. Thank you. Thanks for the question, Thomas. Our next question comes from Derek Archila at Wells Fargo. Please go ahead, Derek. Hey, this is Hao. I'm calling in for Derek Archila. Congrats on the data, and thank you for the question. I guess my question is, given the very promising itching data that envudeucitinib demonstrated and, you know, another biologic is also, you know, regarded as a very good treatment for itch. Any, you know, color you can provide on, you know, the dynamics there and then the potential of, you know, envudeucitinib really be go-to for any patient who has severe itch symptoms? Yeah. I'll just tell you from the commercial standpoint the way we think about it, and then I'll have the clinicians answer as well. From a commercial standpoint, you're absolutely right. We actually do believe that when we had these conversations in the last couple of days with clinicians, they often said there's a shift happening, and they now understand because they've learned from AD that itch can play a key role. We've had several conversations over the last 24 hours at least on how do you make sure that that is actually a key consideration for a psoriasis patient. I think this is what we would describe a little bit of a market maker opportunity because we have the data now, and we were told by many clinicians. Actually, this is a point that a percentage of clinicians understand today. A lot of patients are very eager to understand, and this is the number one symptom they want to be addressed. I think there is a significant opportunity to really take advantage of this itch data. I'll also hand it over to Dr. Blauvelt and then to Jörn for some more comments from the clinician side. I'll just add one bit, Martin, and say, this is the reason. I didn't explain it, I think, fully, but this is one of the reasons why we showed the scalp data. Because if you ask psoriasis patients about where they itch the most, it's often the scalp is the answer. The focus on scalp is important, I think, the data I showed and the itch data. We don't have the ability to do the correlation. We didn't ask in the itch score where the itch was. We just asked about itch. But my suspicion is that that improvement in the scalp is largely related and correlated with the itch improvement, which is important for patients. Thank you. I have really nothing else to add. Thank you. Yeah. Look, from the commercial side, I would just add, you, Dr. Blauvelt mentioned that about 80% of patients actually have itch in the scalp or have scalp disease and therefore have itch in the scalp. I think there is a very significant opportunity here to have segments where this might be the preferred drug. Great. Thanks for the question, Hao. So our next question comes from Iris Gao at Guggenheim. Please go ahead, Iris. Again, congratulations on the data. I would like to ask a question to Dr. Blauvelt, and to double-click on the patient baseline. If you could compare patient baseline from the ONWARD studies with competitor trials and including zasocitinib, that would be really helpful. Thank you. I'm going to refer to the slide. I don't know if we can pull it up again, but I think you'll remember it. Jörn talked about the consistency between the two trials, right? He showed that the icotrokinra data was not quite consistent. Then we also showed that the zasocitinib data is not quite consistent from study 1 to study 2, and ours was. Well, if you delve a little bit deeper in that zasocitinib data and look at their demographics in the study 1 versus 2, one of the things that was striking to me was the percentage of white patients. Normally, these trials, it's about 85%, and that's one of the reasons why we do compare, because the demographics, predominantly white, is similar across studies. In study 1 of zasocitinib, the one with the highest efficacy, they had 60% white patients. We've been told that many patients, non-white, were from China and Japan in those studies. I think I don't know. That almost, to me, disqualifies it in terms of using it as a benchmark. To me, that's a very different population. That's to me. That's my opinion on study one that was presented with zasocitinib. Again, my opinion. I like it when the demographics are similar, and that study has too different of demographics to be a benchmark for me. Yeah. Just to add a little bit to this. I mean, why does it matter, right? We do know that the Caucasian populations on average have a higher body mass index, and they tend to be a little bit more difficult to achieve complete responses. For whatever reason, we often observe that response rates in some Asian countries, including China, tend to be higher. That may have to do with body mass index. It may have to do with how the local standard of care works. It may have to do with other factors that we don't completely understand. It's a reasonably consistent observation. That's obviously something you need to consider as you interpret study results here. What was the population, and, how comparable is it to other studies that you want to compare with? That's very helpful. Thank you both very much. Great. Thanks for the questions, Iris. Our next question comes from Brian Skorney at Baird. Please go ahead, Brian. Hey, good evening, everyone. Congrats on the data as well. My question is also for Dr. Blauvelt. You know, I guess we have now three oral drugs that look like they're on par largely with biologics. Icotrokinra, which just got approved, and now envudeucitinib and zasocitinib. I guess, how do you think about using these three in practice? Do you see them as interchangeable given the data right now? Or, you know, do you perceive a reason why specifically targeting IL-23 would be preferred over TYK2 in some patients versus others, and vice versa? Yeah. I'm gonna just tell you my gut on that answer. First of all, I think there's room for all three. I totally think there's room for all three because we've had 12 biologics for psoriasis. They're all successful. I just think that we haven't had great orals. You know, we've had Otezla, which has been very popular. So the experience of Otezla means that there's many patients that want pills and many doctors that are willing to do pills that are inferior in efficacy. That's what Otezla tells us. With a great drug, three great drugs now, I just see those three drugs taking over all of the Otezla market. I can't imagine the Otezla users continuing to use Otezla with the introduction of these three. Now, one thing, obvious, icotrokinra will have at least a year advance, right? It's first out of the box, so it's gonna have advantage in terms of that. PSA, lupus, it, I think TYK2 inhibition is better than selective IL-23 inhibition, obviously for lupus, but also for psoriatic arthritis. I feel like and that's a common comorbidity. That may be a differentiation point. If the patient has the common comorbidity of PSA, I personally would prefer to use a TYK2 over a selective IL-23. These are some things. Then, of course, availability, right? The non-medical part. If there's discounts, if it's marketed well, if the company that has a drug has a good access with the payers and contracts, all of that is gonna be in the mix with these three drugs as well. An aggressive company that is good at all of that, it's gonna make a difference in terms of market share. Great. Thank you. Thanks for the questions, Brian. Our next question comes from Jeff Jones at Oppenheimer. Please go ahead, Jeff. Jeff, you might be on mute. All right, we'll just go to the next analyst. Our next question goes to Alex Thompson at Stifel. Please go ahead, Alex. Hey, great. Thanks for the question, and congrats as well on the data. I was wondering if you could maybe give a little bit more color on the specific malignancies that you observed in the studies and sort of your confidence that, you know, this is not really above overall background rates here. Thank you. Yeah. I mean, in any large trial set of more than 1,800 patients observed over a long period of time, you will have malignancies. That in and of itself is not a surprise. Really the way to analyze is to compare the exposure-adjusted incidence rate with what is known about the background rate in this population. Then of course, also compare the cases you see in your experimental drug versus the control, be it placebo or be it active control. If we look at the exposure-adjusted incidence rates, these analyses are still in progress, but our preliminary data suggests that these the exposure-adjusted incidence rates that we've observed to date are well within the range what's been reported in this population. It is known that patients with psoriasis have a somewhat elevated risk of cancer. The literature is somewhere in the 20% range increased risk. You need to then compare this and see whether the number of cases you observe is consistent with what you expect in this general population. To date, what we have seen, that was the case. We have not seen an imbalance in between treatment arms, active control, and experimental drug, nor have we seen a rate that exceeds what's been reported in the literature. I wanna add one thing from my experience in doing trials. I don't worry about quote-unquote worry about cancers in the first six months of any study because cancer does not develop in six months. These are patients who had cancer when they came in. They just have been reported in the first six months. It's really a long-term issue, right? Over the long-term data is when we do everything that Jörn just said. It's unrealistic to think that the drug caused anything like cancer, a long occurring disease, in the first six months. All right. Great. Thank you for the question, Alex. Our next question comes from Christopher Raymond at Raymond James. Please go ahead, Chris. Hey, thanks for squeezing us in here, and congrats from us on this data. Maybe just for Dr. Blauvelt, I know you answered the sort of commercial question in how the, you know, these agents might sort of impact your practice. I guess hearing you say there's room for all, right, of these high-efficacy orals. You know, you mentioned that derms would prefer a pill versus biologics. Is there maybe a patient type you might highlight for us that would make more sense or a biologic that you'd pivot away from first? Thanks. Yeah. I think in general, I tend to say, "Is the patient a candidate for systemic therapy?" I tend to lump the pill and the shot choices together and consider them, "What are my systemic options?" However, many patients and many dermatologists out there will use and prefer pills with more moderate disease. They'll think of and use biologics for a more severe patient. There is that view. Of course, we have Otezla went all the way down and got an indication for mild psoriasis, basically having any kind of psoriasis is a candidate for Otezla. I think, I mean, to me, that's where I haven't discussed this with Alumis, but to me, that's where I think Alumis and these new orals should go all the way down to any psoriasis because topical therapy for psoriasis, even one, two plaques. Somebody will say, "Well, it's not enough to treat with a pill." Topical therapy does not work well for psoriasis for a chronic disease. I don't like topical therapy at all for any patients. I think the whole field is actually getting more and more comfortable with this, kind of moving in pills in particular to patients with more mild disease. Great. Thank you. Thanks for the question, Chris. Our next question comes from Katie Degen at H.C. Wainwright. Please go ahead, Katie. Hi, this is Katie Degen on for Mitchell Kapoor. Thinking about dosing between the TYK2 options, is BID really of significance to patients when selecting between those options? How does the ability to hit that single once-a-day dosing really impact your ability and outlook for envudeucitinib? Yeah. I'll start with the perspective from the market research, and then maybe Dr. Blauvelt can also talk about this. We all realized that actually, even Otezla was twice a day for the longest time and really didn't have any issues. When we did our market research prior to the data release, it turns out that we lose about 10%-15% because of the BID versus the once a day. I think it's really also dependent on what the other factors are, and we'll go out there and now do additional market research. I think it's also a question of how you position the molecule. It is important for us to go after once a day, and we're developing a once a day. Is it the most critical reason for people to actually select a drug? In our market research, that BID versus once a day is actually quite far down. Three times a day would be a different story, but BID seems to be something that people are just used to. In the market research, at least we see that. I'd love to hear Dr. Blauvelt's view as well, what he sees from his patients, whether twice a day has been a hindrance in the past. I'm just gonna make a quick comment and say it's not a killer. It doesn't kill a drug that is twice a day. There's many twice-a-day drugs, right? So it doesn't kill the drug. Yes, it's preferable to have once a day, I agree with that. I like the idea that we're moving towards a once-a-day formulation. It will help, but twice a day does not kill it. Not at all. Hey, Tara, I think we have time for one more question. Can we please go back to Jeff Jones? I think his line cut out earlier. Yes. He should be good now. Go ahead, Jeff. Hi, guys. Can you hear me now? Yeah, we can. Yes, we can. Great. Sorry about that. Internet cut out. One just efficacy clarification, or population question. In looking at the bio-experienced or you defined them as systemic psoriasis treatment, and Takeda described them as bio-experienced. Can you give a little bit of clarity on what you meant by patients on systemic psoriasis treatment, and if you saw any differences in responses in that subgroup? Yeah. Let me clarify this for you. Our definition of prior systemic therapy included not only biologicals but also oral. Say, for example, had previously been treated with a JAK inhibitor or with another systemic oral, they would fall into this category. If we just look at the proportion of patients that had previously been on a biologic, that would be closer to about, I think it was roughly 25%. That was between 25% and 30%, actually. For the ONWARD trials. It's just a question of definition, how do you define it. That is often. Thanks ... used as a marker of how severe the population was. If they were heavily bio-experienced, we consider them tougher to treat. For me, the biggest difference in the zasocitinib and envudeucitinib data is, in this regard, the percentage of moderates versus the percentage of severes of PGA. Alumis had 70% moderate patients and 30% severe, and the zasocitinib numbers look like they're 80% moderates and 20% severes. To me, that means they had an easier-to-treat population. Appreciate that very much. Thank you. Great. Thanks for the question, Jeff. This concludes our Q&A session. Martin, I'll turn it back over to you for closing remarks. Well, thanks, everybody, for joining us today, and we certainly are extremely excited about the data that we have shared. We really believe that this is exceptional data and will be helpful for patients. As we shared, I think the most important thing is, for us, this is one milestone achieved, but also the beginning of additional opportunities for patients and for envudeucitinib and our TYK2 franchise. We look forward to sharing more information with you down the road. As I mentioned, we will have additional data for envudeucitinib in psoriasis in the second half of this year. We look forward to sharing that with you and wanna thank everybody for participating and wish everybody a good evening tonight. Thank you very much. Okay. We are out. All right. Great job, guys. No longer live. Thank you so much. Thank you. Andy, great job. Bjorn, great job. Martin, good job. Great job. Really good. It's okay. Mine was only good. That's fine.