All right, I think we're gonna go ahead and get started. Good morning, everyone. Welcome to Guggenheim Emerging Outlook Biotech Summit 2026. My name is Yatin Suneja, one of the biotech analysts here at the firm. It is my pleasure to host our first presenting company today, Alumis. From the company, we have two executives here who I will be moderating a discussion with. We have President and Chief Executive Officer, Martin Babler. We also have the Chief Financial Officer, John Schroer. Martin, why don't you make some opening comments? You know, obviously, very good results that you recently provided earlier this year. Just tell us maybe recap the results a little bit, if you could, talk about some of the milestones that are coming up, and then I'll have some Q&A for you. Yeah. Okay. Well, first of all, thanks for having us. It's always a pleasure to be here, and as you just said, it's a perfect timing for us as well. So Alumis is a precision immunology company, first and foremost, and when we did our very early work, TYK2 actually came to the top as one of the most interesting targets, just from a genomic standpoint, because it's so genomically rich. And so we pursued several TYK2 inhibitors that are now in the clinic. We have one peripheral molecule and one brain-penetrant molecule. I apologize. So what we just announced is for envudeucitinib, we have phase III results in psoriasis. Those results were really how we expected the molecule to perform. We saw a very strong reduction in PASI scores. We saw PASI 75 that we made public that was basically in the 70s. We We said at week 24, we have PASI 90 and PASI 100 of about 65%, and over 40% for PASI 100. We also shared in our press release that we have a fast onset. We basically see a separation of PASI 90 and PASI 75 already at week 4, and we saw a safety profile that's very consistent with what we've seen in our phase II data set, no new safety signals for the molecule. And so we do believe we have a highly competitive molecule for the oral psoriasis space, with a molecule that doesn't just have benefits on lesion reduction, but also has really nice benefits in terms of quality of life, in terms of itch resolution, et cetera, et cetera. And, we have submitted an abstract for AAD this year. Whether that will be accepted or not is, up to the AAD, but we hope we'll be able to present that data set and some additional information at that point in time. Got it. Very good, thank you for that. I think you mentioned some of these data that you announced. So you disclosed just very, very top-line data, 16-week data on certain endpoints, 24-, 24-week data on certain endpoint. What was the rationale behind that? Yeah, so first, I have to start by saying, understandably, the medical societies are becoming very strict, and they feel like if all the data is already out there, why should they have a late breaker? And given we wanted to have a late breaker at AAD, we had to limit the amount of information. And so we were very thoughtful about what is it that actually the physicians will want to see and what would give you, as investors the best possible picture. The primary endpoint for our trial is PASI 75 at week 16, and we shared that information. What we heard from physicians, however, is that the way that they assess molecules in this space today is really PASI 90 and 100 at week 24. We've also heard the same from analysts, and so we felt like if we give you that information, that will be helpful. Got it. Also, we heard from people they will want to understand the speed of onset, so we basically alluded to that, and we wanted to make sure that people understand our safety. So it's a balance between what can you disclose and still hopefully get a late breaker, and giving enough information to give a decent picture. And I think where we ended up actually is in a relatively good spot because we do have MSLs active in the field, and they at least can now have preliminary conversations with physicians about this data set, and that enabled us to at least have an ability to communicate to everybody a picture of what we have with our results without giving away all the data. Got it. Got it. So the other question generally we get from investors, and the people that we talk to is, placebo, right? I think obviously no disclosure there. How would you put the placebo response in historical context, whether it's PASI 75, 90, or 100? So, on the what we've shared in the Q&A is that on the PASI 90 and PASI 100, we are very much in line with what we've seen with recent trials. So you're below 5% for your PASI 90, you're about 1% or below for your PASI 100. Those are historical numbers that we've seen, and I think we're very much aligned with that. On the PASI 75, we have shared that one of our trials actually had a higher placebo rate, a higher active rate, and a higher comparator rate, but if you actually placebo adjust or active adjust the data between the two trials, it's very consistent. Got it. Got it. So you touched on speed of onset. That's something you wanted to emphasize on. Why? What, what is the reason? Is it something to do with the mechanism, or is it because of Taltz or SOTYKTU, like, why you wanted to make that emphasis? Yeah, so, this is an interesting one because when our team basically talked to site leaders or to a dermatologist, what we hear a lot was that a nickname for Sotyktu, though, was Slow-tyktu. And so we wanted to make sure that people really understand that that is not... that's pharmacology-related, and it is not mechanism-related. And so, we've always gotten a lot of questions around the speed of onset, and while dermatologists really care mostly about what happens in the long term and where does the PASI scores, where do the PASI scores end up? The speed of onset plays somewhat of a role, and what we wanted to make sure is that people understand that the speed of onset of our molecule is very much in line with other molecules, and we have actually a relatively fast onset. I think the other piece there that we have shared in the Q&A a little bit is that we see a really strong reduction in itch, which is the number one symptom that patients and physicians care about. And that speed of onset actually is surprisingly faster than it is even for the plaque reduction. And a lot of physicians always thought that they would go hand in hand, but they actually don't. Got it. Got it. How would you characterize the baseline patient population relative to IL-23, like the peptide, or the Takeda molecule? Exactly. So we don't have enough information on some of- Yeah those competitors. But when you look across these trials that have been completed recently, in psoriasis, whether it's for oral or injectables, we actually believe, given those trials are relatively large and they are actually global trials in most cases you see very, very similar demographics. And so I think we were, we're very much in line. What we see is that we have a little bit more severe patients in our study than you see in the other studies. So that's probably the one aspect where you, you'll see a slight difference. But overall, I would say it's very much in line with what you've seen in recent studies. It is a population that has a lower BMI, and less biologic experience than we've seen in our phase II, and that might have contributed a little bit to the notion that some people have that, "Hey, is this data better than our phase II data? Got it. Got it. Very good. So then at the AAD, what we should be focusing on, what do you think should be the takeaway, for, for investors? I think at AAD, the most important aspects are on the efficacy side, there's really two categories that will be important. The first one is just what is... What does the effect on plaques look like? I see. And we believe that we're very competitive there. Then we do believe that there's additional benefits that TYK2 mechanism, that the TYK2 mechanism have, and that's around quality of life, that's around other wellbeing aspects. Mm-hmm. And then the third one is the safety. Yeah where we basically believe that we have a competitive safety profile. Got it. Got it. So let's just go into the market dynamics. I mean, we understand right now there is only one drug, Sotyktu, which has done very well. So TYK2, we can all debate what happened there, maybe not the suboptimal molecule. But how do you envision the, the psoriasis market shaping up? Because it's not only you. I think if you look at Iko is going to be there, you are going to be there, and zasocitinib, they're from Takeda. So how do you see the positioning, the relative share, the expansion of just the psoriasis specific market in the U.S.? Let me start with a broader picture maybe first. Yeah. We should not forget that even today, the patient share of oral drugs is actually higher than the patient share of injectable drugs. Yeah. There is more patients on oral drugs today than there are on injectable drugs. The even larger portion of patients is actually on topicals. And so I think there, what you will see is a change in market dynamics. Because despite the fact that they were not very efficacious, patients still preferred oral drugs. And we know from market research that about 75% of psoriasis patients would rather have a pill than they would have Yeah An injectable or even a topical for that matter. So we believe what will happen is that the oral market will actually expand quite considerably, because patients that currently are on topicals but have a relatively high body surface area might actually switch to an oral. And we believe that patients will stay on oral longer, and the injectable will become more like the backup plan rather than the mainstay of therapy. Yeah. So across the board, we do believe that the percent of- Yeah Patients that is on orals will actually significantly expand. And within that group, I think it's going to be a matter of preference, and it's gonna be a matter of what patient type it is. We do believe that for patients that really have, for example, scalp involvement where itch is a considerable concern, because if you itch on your head all the time, you want that to go away. We could see that we actually have a better positioning there. And there's other patients that might have other aspects where another molecule might be more prominent in use. But I think our overall profile is a very strong profile when it comes to that, because we see very strong reduction in plaques. You know, we are at more than 40% of our patients basically that have a clinical cure, if you so want. Got it. And then we have these other aspects, whether that is quality of life, et cetera, et cetera, and we'll share more data that we believe will make it clear to folks where we might have a an advantage over these other molecules. And then I think the ultimate aspect is also the simplicity and convenience, and this is an aspect we just don't understand yet, because we don't know how these other molecules are going to be launching and- Yeah And priced, et cetera, et cetera. Those all play a role. Got it. Then in terms of, the next step, what are the next step, or when could you file an NDA? What is left? I mean, you really remarkably closed the gap with Takeda, despite starting very late. So just curious, the time to market. Yeah. So what we have guided to is that we are filing in the second half of this year. The main critical path item for that is to have durability and maintenance in the label. We have to conclude our withdrawal part of the study. That is happening as part of ONWARD 3, which is our long-term extension. So the first 200 patients that went into this long-term extension actually were re-randomized, and we had a randomized withdrawal. That data will be available in the second quarter, early third quarter, and as soon as we have that data, we'll finalize our NDA, and ultimately file it in the second half of the year. The other pieces that will come this year still is we will have long-term data, 48-week data, which we believe is also going to be an important factor across the different molecules. And then we will have other additional data, such as biomarker data, and special area data, et cetera, et cetera. So there will be additional pieces to complete the picture, and that data will be released later this year, and then the filing is expected in the second half of- So you could be in the market, let's say, second half or middle of next year, depending on when you file it, right? So how is the commercial prep? What is the infrastructure gonna look like? Can you do it on your own? Yeah. So we basically have the capability and the capacity right now to do all the market prep that has to happen at the time frame where we are pre-market. As I mentioned, we already have a team of MSLs out there. We have a medical affairs department, we have a commercial department. Could we do it on our own? Yes, we do believe that's possible. However, we believe actually the question is not about launching psoriasis or not. We are firm believers now with our data in hand and with other data that we've generated, that this is actually a very significant opportunity across up to 20 different indications. And so the question is: How do you optimize our TYK2 franchise now? How do you do that when you have two TYK2 inhibitors, when you have so many indications you could go after? And is it likely that we can do that on our own on a global level with so many indications? The answer to that is probably, that's not gonna be easy. Yeah. We do believe that a partnership is more likely an outcome. But we are doing everything right now to make sure we're well prepared for a market entry. And there are examples, recent launches from... whether this is from Arcutis or whether that's from Sun Pharma, where smaller companies have been able to do that. Did it have the same outcome than- Yeah If they had a larger support infrastructure? I don't know, but we do believe it's possible, but it's probably unlikely. Yeah. Got it. Okay, so that's it on the psoriasis side. I think this year, we're going to have a lot more data for TYK2 class in general, not only lupus, but I think Sjögren might come this year, a couple of studies in IBD happening. But for you specifically, SLE, I think that was the focus even for last year. So just help me understand the role, or put any of the preclinical and clinical data for other TYK2 in context of SLE. Yeah. So SLE for, we believe for, TYK2, is a very interesting indication. The first set of data that really leads to validation here is the genomics, where you actually see almost the same kind of protective effect, as you see for psoriasis in lupus. There is a specific mutations to P1104A, a mutation, in about 3%-5% of Caucasians, a little bit less in other ethnicities. But people who have that mutation are protected from lupus almost as well as they are protected from psoriasis. So we have really good genomic validation. We have the validation from deucravacitinib, where all three doses basically showed positive effect on lupus patients. And then we have anifrolumab, which basically is a great validation for the mechanism, which is the interferon mechanism. Yeah. We do believe that from a scientific standpoint, lupus is very, very intriguing for TYK2, and then it's more about how you perform the trial. We shared that we will have results from our phase IIb, which is actually run as a pivotal trial in the third quarter of this year. And to your point, there will be other data sets from different indications. So we believe not only will we have interesting data on lupus later this year, and have done everything we could in terms of how we performed the trial to really minimize the placebo effect there, but we'll also get additional information from some other indications from our, Yeah Competitors that might make this, a lot clearer to folks- Yeah How broad TYK2 could be. But could you touch a little bit more on the LUMA study, just from the execution standpoint? Like, what exactly are you doing to make sure you are optimized for success? I know Jörn is running that, and he has some prior experience. So if you can just put that all in context. Yeah. We're very fortunate to have Jörn Drappa, our CMO, who has basically been... He calls himself a lupologist and has been doing lupus trials for the last 20+ years. And so he's done a lot of analysis. And when you look at the execution, we've done a lot of key things, but the three most important ones that probably we keep on emphasizing, and he certainly will share, are: The first one is you have to enroll the right patients. And so we do actually have an adjudication panel that really looks very carefully at the patients. They have to have active disease, they have to have the right symptoms, et cetera, et cetera. And so we really make sure that we select the patients right. The second one is, you have to make sure that you're very aware of what happens with concomitant meds, and how do you optimize for that? Part of that is steroids, which play a key role here, and we did put a steroid taper in place. And it's important to understand that if you can't taper your steroids, you basically are considered a non-responder because we just believe that that, if they can't reduce the steroids, then you know that the drug doesn't do its job. And then the third one is really the tools that we use in lupus are very crude and very complex, and so we address this in two ways. The first way is that we basically build almost like a crawler that goes over the data all the time, and if there is actually discrepancies in what gets reported, we can go back to the site right away and really adjudicate the information, and we can also retrain the site. And that's the second thing we've done. We've had a team go around the world several times at this point, and really re-educate sites on these measurements. And then the last piece is really, I think, one of the pieces that we believe was important for this trial, particularly is that we did choose BICLA as the primary endpoint, and we actually do believe that that was an important decision. Because, especially with TYK2s, we know that it has a really good effect on skin manifestations. And so if you have patients that have skin manifestations, you want to capture that right. And in the case of BICLA, actually, that is a graded assessment versus in the SRI-4, where this is basically a one zero kind of assessment, and that's actually why we chose that endpoint. Got it. On BICLA scale, what do we see with placebo, and what, how would you characterize a success in this study? What sort of, placebo-adjusted delta on BICLA? Yeah, so we see placebo rates anywhere in these trials, as you know, from 20%-60% these days. And so in our minds, actually, we hope that our placebo rate will be more on the lower end- Yeah And we do believe a success is actually if we get similar improvements as you see with anifrolumab, which is about 15%. Mid-teens, basically. So if this is an oral version of the efficacy of anifrolumab, we actually believe that's already success in lupus. Got it. Got it. And then so this is a pretty large study, right? Is it a phase II study or a phase III study, or how are you characterizing it? It's designed as a pivotal study. Okay. It's over 400 patients. Yeah. So we believe that it is, from a design standpoint, it's a 48-week, relatively large study. If you ask Jörn, he will tell you that, you know, you either have to go big or go home in lupus, otherwise, you're not gonna get a clear answer. At the same time, though, the winning group ultimately will have 100 patients in it. Yeah. And so it is a phase. It's a pivotal study. We believe that our base case, at this point at least, is that we would possibly only have to run one more phase III. And the question we always get is: could this be, like, the one registrational study? And I think if the results are really outstanding, that's possible, but the likelihood that you're going to have 100 patients that will be sufficient to get a drug approved is relatively low. Yeah. It would really have to be outstanding data. So from our standpoint, it's a well-designed study, it's a well-powered study, but we are, as a base case, currently assuming that we'll do one more phase III after that. Got it. Got it. Very good. Then into other indications that you are thinking of pursuing, like, what is the strategy? Obviously, there is a lot you can do with psoriasis and SLE, but you said 20+ indications. So where are you thinking of going next? Are you waiting for any competitors' data before you move into those areas? So there is really three pieces to this. The first one is, how do we optimize psoriasis? There are some additional studies we can do, whether that's even psoriatic arthritis or others, that really optimize the psoriasis picture. Then there's a second group of indications that are on the rheumatology side that we will find out later in the year around interferon. So if we have a positive lupus data set, we will know that we can also not only go after IL-23-driven indications, but we can now go after interferon-driven indications as well. And so we're probably waiting more for some of those indications to see our own lupus data. And then we will get an interesting answer from zasocitinib later this year, which is, if you really hit this target hard, can you actually see good results in IBD? IBD. The genomics would actually tell you that you have to hit that target extremely hard, but if you do so, you should get a good outcome, because when you look at the genomics, the heterozygous carriers of that mutation actually don't see any benefit- That makes sense. But the homozygous carriers see about an 80% protective effect. So that tells you that given that that mutation really only affects the kinase function, you have to hit it really hard. And so I think we'll get the answer to that question later this year, and we'll see at what how that comes out. But for us, the most important ones are the ones that combine with, with psoriasis, and then the ones that are driven by interferon. Correct. And then the IL-22 side is really a question of, is IBD in or out on that? And how do you go about that? But there's definitely a lot of very interesting indications, both from a, from a genomic side, but also from a clinical side. What about PSA? PSA, in our minds, is what really combines well with psoriasis. Psoriasis. Yeah. Yeah. Yeah. Yeah. Yeah. Okay, for your brain-penetrant TYK2, what are the next step there? When are you thinking of initiating the RMS study? And could you maybe put in context either the biology or the rationale versus, let's say, TYK2's BTK or S1Ps in the MS? Yeah, so we have a lot of experience with the BTK side, given that we developed, or the team that is now Alumis developed, tolebrutinib at Principia. What we've seen in the preclinical setting is that this is a way stronger anti-inflammatory drug. So in the EAE model, we can actually not induce inflammation if we give a high dose of our molecule. And so what we believe is you get the benefit of the microglial effect, which is really what helps with disability, and then you get the inflammation, the anti-inflammatory effect, which really helps with relapse rates. And so we do believe that there's a really interesting pharmacological and biological rationale here for TYK2. Our intent is to start the study in the first half of this year, and basically move forward with MS as part of the overall package. I think the other piece about this second molecule is, it gives us a lot more flexibility around pricing, around timing- Yeah around IRA, et cetera. So there might be also other indications that we're pursuing with that molecule, and not just MS. Got it. John, how is the balance sheet? I think you raised capital recently. How are you positioned now? Because, you know, I think as you're expanding the indication and commercial prep, how are you, what's the cash runway? So we came into the year with cash on the balance sheet and with the proceeds of the follow-on offering, that gives us just over $630 million. We have a very strong balance sheet to support the operations of the company and the expansion of the pipeline, and that will provide us runway into the fourth quarter of 2027. Very good. So very good. Gentlemen, thank you so much. Thank you. Thank you.