Great. Thanks for joining us everybody. I'm Terence Flynn, Morgan Stanley's U.S. BioPharma analyst. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. This morning, I'm very pleased to be hosting Alumis. Joining us from the company, we have Martin Babler, the company's CEO and Chairman of the Board, and Jörn Drappa, who's the company's Chief Medical Officer. Thanks so much both for being here. Really appreciate it, early on a Monday morning. Maybe first, I figured we'd start with the company's key asset, which is envu. One of the questions we get a lot is on the oral psoriasis space. There's a couple of other competitors out there. So maybe just high level, walk us through kind of the profile of what you guys have seen in your phase III psoriasis data versus Takeda and also J&J's ICOTYDE. Because those are the kind of key other competitors that I know everyone's focused here as the landscape continues to evolve. Well, Terence, thanks for having us, and happy to go a little bit into psoriasis. So yes, envu is a TYK2 inhibitor. We believe that actually in TYK2 inhibition, one of the most critical things in psoriasis is that you maximally inhibit the target. I think our data has been actually extremely consistent. I think that's actually the one piece that we feel we're very proud of. What we see with envu is that we consistently see basically PASI 100 rates in 40% or more at week 24. We actually do believe that the predictability of the molecule and the consistency of the data is an important aspect. The fact that actually fundamentally we put about 40% of patients into a state of clinical cure at week 24, then in our ONWARD3 trial where people were able to choose to go into, we see that rate actually going up in the ONWARD3 section overall to about 54%. If you actually take a complete ITT analysis from the very beginning of our ONWARD program all the way through the end at week 48, you're actually getting close to 50% as well of patients getting PASI 100. So almost half of the patients actually with this drug basically get clinical cure. The other aspect that we feel is very important is actually when you ask patient what their most important symptom is that they want to take care of, they will actually tell you it's itch. Physicians don't always agree with them, because itch in psoriasis is actually a matter of disrupting the plaque. But for patients, that's a very important symptom, and we've shown consistently in our data set that for itch, we have a very strong onset. That means it resolves very fast, a lot faster than the plaque, which is where physicians thought the resolution of itch comes from. But not only does it resolve very fast, but we actually use the NRS scale to measure it, which is what other people have used in itch trials for atopic dermatitis. And the FDA perceives the four point or more improvement as really clinically very meaningful and improvable. And we've actually seen the four point improvement in a very large number of patients, over 70%. Great. Maybe just talk to us about the filing here. What's gating to getting this into the FDA, and what's the expectation in terms of turnaround time? We are guided to filing in the fourth quarter. We are on track to do that. One of the things that we can now publicly say also is that the FDA asks you to contribute safety from all ongoing trials. So one of the pieces that actually we were looking to get was the safety from the LUMUS trial, and we could have done that as just a cutoff point. But we felt actually understanding the LUMUS safety data, including the placebo responses, was helpful. And we've shared that one of the key outcomes for us for LUMUS, which was a lupus trial, which is normally a sicker patient population, also on other concomitant meds, basically showed us that it was again, very well tolerated. We saw no new safety signals. We have publicly disclosed. We saw no MACE, we saw no malignancies, no blood chemistry elevations that would lead to a potential risk of monitoring or anything. So we actually do believe the LUMUS safety data makes the case for envu even stronger. And that was the last piece that we needed to finalize the NDA. Okay. Is it fair to assume standard review timelines? Is that how we should benchmark in terms of turnaround time? At this point, we should assume a standard review timeline. Okay. One of the other questions we get is about the label. I think you guys have made the case about more selective inhibition of TYK2 versus SOTYKTU. Maybe talk to us about likelihood that you will have a differentiated label versus SOTYKTU, because again, I think that is another debate that we hear from a lot of investors. Yeah. Jörn, you want to start? Yeah. I think SOTYKTU still had some carryover language from JAK inhibitors. I think both us and Takeda as well have consistently shown that with selective inhibition, you really do not have any JAK inhibition. Possible side effects of JAK inhibitors would be blood cell abnormalities. There would be lipid elevations, this type of thing. Consistently across both molecules, Takeda's and ours, we have not seen any evidence of that. We have had extensive early clinical development where we also have carefully tested whether there is any evidence of JAK inhibition. There is none. It is fundamentally a different pathway, so we will certainly make the case that we should have a label that reflects our actual data. There is no hint of anything related to JAK inhibition in our data set. The other one is the TB issue. I think what we have now seen is two really interesting data points. First, neither us nor Takeda have shown any TB reactivation in any of our trials to date. The other one is [audio distortion], which is a [audio distortion], basically just got a labeling where it is very similar to ICOTYDE, where the label actually is not a requirement for TB testing, but rather just a recommendation. We believe that is actually a good surrogate for us to look at, that we believe we have a good chance to also get that kind of labeling. Great. I think Takeda is a little bit ahead of you guys in terms of filing timelines, so it seems like they will probably get their label first. Should we assume whatever they get, you guys will get something very similar, or is there enough differential to say, "Okay, because Takeda got X, envu might get Y"? I would say that the label is based on the entirety of the clinical data, right? I can only talk about our clinical data since all I know about Takeda is what they have published. Based on our clinical data, we expect no requirement for lab monitoring, because there are no systematic excursions in lab values. Martin has talked about the TB, and the overall safety and tolerability looks excellent. I think the label is going to be based on the data set. Okay, fair enough. Last one, just the psoriasis side is any progress with the once-daily formulation? I know that's another thing going on in the background here, so maybe just level set us on where things stand there. Yeah. Our plan was originally to just share once we have selected the formulation so we could give you an exact timeline. But I think we decided last week that we actually have disclosed that we are taking multiple formulations into the clinic in the near term, and then we'll make a decision which one of those we're moving forward. We shared before that we actually made one formulation that we were very happy with from a PK perspective. Unfortunately, it had one other flaw that we just didn't like. We have since worked around that and basically are hoping to identify a formulation once we've done with the clinical testing, and then we can give you exact timeline at what point we will have a once-a-day formulation. How long would that initial PK/PD work take? Are we talking months here, or is this quarters roughly? This is probably quarters, because we want to be very solid on that. Yeah. Okay, got it. Okay. Maybe just moving to the more recent news, as you mentioned the LUMUS trial, Martin. Maybe just for everyone who hasn't gone through that data, walk us through the key messages from the phase II data set and the next steps, because I know that's something else that you guys are focused on. Sure. This was a 48 week phase II-B dose ranging trial, pretty substantial in size. Four arms, 100 patients each, including one placebo arm and three active doses. Primary endpoint was the BICLA, which is a composite measure of disease activity in lupus at week 48. The headline result was that the trial did not meet its primary and key secondary endpoints in the overall all-comers trial population, but there was a strong signal in a predefined subgroup, which is the patients who have evidence of what we call the interferon signature. That's a subpopulation that constitutes approximately three-quarters of moderately to active lupus patients overall in prospective studies. We had pre-specified this, but we had not a priori excluded the biomarker-negative, the interferon signature-negative patients, because we did not have a priori evidence that there would not be at least some benefit in those patients. Bottom line was that for the interferon signature-negative patients, there was no benefit. In fact, for some endpoints, the placebo response was actually higher than the active doses. There was a strong signal in the interferon signature positive subpopulation, and so there was a separation from placebo, both for the BILAG, for the SRI-4, which is another composite endpoint in lupus for skin rashes, for joint counts, for remission. Consistent evidence of response. Going forward, I think it's going to be important to hone in on this population that is likely to benefit from type 1 interferon-targeted treatments and focus the analysis on this subpopulation. Then just from an end of phase II meeting, any timelines around that? Because I think that's, The data is still new. We are still digging through it, including some aspects that we need to understand further, such as dose response, proposed phase III doses, et cetera. We are aiming to put together a package for the agency by the end of this year, and then request a meeting. That's probably going to be early next year, given the busy schedule for the agency, typically in December. That's the plan forward. We want to get an understanding of the agency's position on several questions. One question is for enriching the biomarker-positive population, what is the better strategy? Is it to basically focus the trial on this population in the first place, or would their preference be to have still an all-comers phase II-B trial with a cap, for example, on the signature-negative patients, then having the primary analysis for the biomarker-positive population and then the all-comers as a secondary analysis? These are two possible approaches. We need to get buy-in on dose selection for phase III and several other aspects. Those would be the key topics of discussion. Do you have all the data you need to go higher in dose if you guys did want to do that, meaning from your prior dose escalation work, do you have more headroom to take the dose up if you decide to do that in phase III? Yeah. The data does not really suggest there would be any benefit. In fact, one of the surprises of this trial was that the dose response was somewhat attenuated. We did have a bit of a dose response within the BICLA, but for other endpoints, there was a lot of variability, and the overall effect size did not seem to be very different between the middle and the higher dose. I think if anything, the question would be whether a lower dose would go forward and not a higher one, in this disease at least. Yeah. Just to add a few other things, because we had an original timeline if the trial was positive just in the first place, and we didn't have to do pre-specified subgroups. From a timeline and from a trial size perspective, actually, we do believe that there is really good evidence here that we could stay relatively close to what our original plan was. We originally had shared that as a base case, we would have to do one additional trial. We'll certainly see whether that's still an option. I think the other piece that's important for people to understand is we do not expect a significantly larger trial than what we've already performed, because for the LUMUS trial, we actually collected quite a lot of safety data across all four doses. But the long-term extension was actually all in the highest dose. We do believe that we can actually size the trial for efficacy and don't necessarily have to size it for safety given the way that LUMUS was structured. Anything else on the placebo arms or minimization of placebo response? I know that's historically been a big focus for lupus trials. As you look through, I know it's still early days, but as you look through the LUMUS data, anything more you think you can do in terms of an implementation standpoint to mitigate that placebo response further? Yeah. I think the key again is going to be the biomarker selection, right? Our placebo responses in this trial were high, but they were entirely driven by the signature-negative patients. Within the positive population, the placebo responses were in the high 20s, which is within the realm of the expected in lupus trials. I think, again, sufficient disease activity, ideally by BILAG A's at enrollment and the interferon signature, both of which are highly correlated with one another, are the best ways to minimize placebo responses. We already did undertake very significant efforts to try and do this through enrollment adjudication and real-time data review and other things. But it does turn out that this population that lacks the interferon signature does have very high placebo responses, and that corroborates prior experiences from anifrolumab where the same thing was shown, and in other trials as well. As you think about, I guess, the interferon signature, is that just a blood test, so it's very easy? Do most lupus patients have that done during the course of their regular diagnostic workup, or is that something that would be an extra step that doctors would have to do as we think about commercial implications for looking for that? At the moment, that is still very much a clinical trials blood test, but it is a commercially available blood test that is offered by the large central labs such as PPD and Covance and others. It's nothing that we invented. We just utilized that commercially available test. I think going forward, as more and more evidence is generated that especially type 1 interferon-targeted therapies just do not work in the negative population, that this is going to become more common as part of clinical workup in the future. Okay, great. You can actually already see a little bit of a precursor of that, because if you type in lupus and if you go do your search on the web, it turns out there's already pop-ups happening for interferon testing if you're a patient that has been diagnosed with lupus. So it looks like at least there's a directional effort going on to assess interferon high or low status already today. Okay. We were talking about this earlier. Bristol-Myers has some data for their first-gen TYK2 in SLE expected later this year from two phase III trials. As you think about that data, maybe just frame for us the range of outcomes and what it would mean for your phase III strategy and anything you would be focused on. Yeah. If you look at their phase II PAISLEY trial, there was quite a bit of variability in between the dose arms. The delta in responses between active and placebo ranged from, I think it was 26% at the lowest dose, and then it was single digits, and as they doubled the dose, and again went up to 15% when they tested the 12 milligrams. That is quite a wide range of outcomes, and it will be interesting to see in phase III on what end of this large spectrum their results are going to come out. If it turns out to be on the lower end, I think there is a clear path forward. If it is at the very high end, then I think that makes it more challenging because they are going to be several years ahead. That will need to factor into our decision-making of where and how to move forward with the type one interferon-mediated group of diseases. Okay. Are they looking at, I guess it is not your trial, so kind of an unfair question, but are they cutting it by interferon signature as well, or do you guys have any insights there? Not that we're aware of, but I don't have any further knowledge than that. Okay. They have done the analysis that way post-hoc. Okay. Whether our data suggests that they might do something different in their analysis plan, we just don't know. Okay. Fair enough. Maybe just high level, what are the implications of these data for other indications? I know you guys have a plan to think about other indications for envu beyond psoriasis, beyond lupus. So what do these data mean for that plan, I guess? We publicly disclosed that we are interested in pursuing CLE and Sjögren's. For both of these diseases, there is the same kind of dichotomy between the interferon signature positive and negative. I think it's going to have implications for those indications as well, and we'll need to carefully consider how we implement the learnings from this phase II trial into any future trials and really try and focus the analysis on those patients who are most likely to respond. I think there's probably, at this point, insufficient justification to exclude, for example, signature negative patients in a Sjögren's, because we have no prior clinical evidence that there's not going to be some benefit. But we'll certainly need to carefully think about how to construct outcomes and statistical analysis plans. What would any rough timelines for those two indications as you think about the phase II rollout 27? I think we want to carefully evaluate our phase II lupus trial first and finish that work, have the interactions with the agency, and determine the best path forward before we comment on any timelines there. Okay. Takeda has, with zasocitinib, their next gen TYK2 inhibitor, some IBD data coming from two phase II trials. I know you guys, was not an indication that you prioritize, maybe just talk to us about that decision, but then also what do these data mean for you guys and envu in terms of any learnings or implications for other indications you might pursue? In principle, IBD is an obvious application for a TYK2 inhibitor. We know that IL-23 inhibitors work in ulcerative colitis and Crohn's disease. The question is, as a monotherapy, are they going to be able to break through this efficacy ceiling that we have consistently seen with other treatments? It's going to be really interesting to see that data. The other thing that we've been working on in our research group is on what would be a rational combination approach in IBD. Because in my view, since we have this relatively low efficacy ceiling that nobody has been able to break through, probably the way of the future is to explore combinations between orthogonal pathways and see whether that can actually lead to a real quantum leap in remission and clinical response rates in this disease. That's something that we're very much interested in. Any pathways in particular that kind of jump towards the top of the list? We've looked at a number of pathways, and I'm not sure whether we want to go to any further details than that. Okay. Would you try to do an oral/oral combo, or it could be oral injectable? What would be the ideal, I guess? The ideal in my mind would be an oral/oral, because it is certainly more challenging, both from a cost and from a logistics perspective, to have an injectable and an oral. Yeah. Okay. I just want to reemphasize, we have actually done a lot of work around this, so we do have pretty strong opinions of what we should be doing. We are not sharing that at this point in time. Yeah. Okay. Maybe just high level as we think about the market opportunity here in psoriasis and SLE, Martin, you could just walk us through kind of where you think this drug has the potential to generate in terms of sales or maybe any analogs we should consider as we think about those two opportunities on the commercial side. Yeah. Part of this is really are we launching this ourselves or are we launching this with a partner? We do believe there is significant opportunity. The way I describe this to people is that currently J&J believes that ICOTYDE could be $6 billion in psoriasis alone. Takeda sees about $3 billion for psoriasis alone. We have a molecule that really shines compared to those molecules in terms of efficacy. We have very strong evidence in some subsets of patients, especially those with a lot of itch. We do believe there's significant opportunity for us as well in this market. It's a market that's quite fragmented. If you look at the IL-23s as an analog, even a very inferior IL-23 still approaches $1 billion in sales. We do believe that there's very substantial opportunity. The question is how we best realize that opportunity, is that alone or in a partnership? We always said our plan was to partner the asset, but as a fallback, there's certainly the situation where we could also launch this probably ourselves in the U.S. and then figure out what we do with the rest of the world. From our standpoint, just psoriasis alone is very substantial. The lupus market has a very high unmet need. Yes, there is quite a competition now for who gets the first oral approved and there's some competition around basically what mechanism might be viable. The reality is, so far, most of these drugs have about an efficacy rate of maybe 20%, maybe 30%. That still leaves a lot of room open. We do believe there's substantial opportunity both on the interferon side and on the IL-23 side. I think the other piece that we haven't talked about is that our lupus trial also basically showed us that we suppress interferon quite substantially. There's other indications, certainly outside of the ones that we just talked about, that are driven by interferon that we could also tap into. You mentioned this, the potential partnerships. Maybe what are the important inputs or considerations as we think about the profile, the timing of a partnership, maybe just some of the variables that you're considering here. You mentioned U.S. versus partnering ex-U.S. How do you think about the different inputs that we need to think about? Yeah. So in the ideal world, you find a partner that shares our vision for this molecule across many different indications and on a global level, and we play a role in that relationship as a partner. I think at the end of the day, this is going to depend a little bit. We were hoping that the lupus data would be a clear help to clarify what we're actually basically partnering for. I think the data was a little bit more mixed, so it's not as black and white. But we certainly have now more information in our hands to have these discussions with people about what a partnership could look like. We believe this could be anything from what we've done in Japan, where we just basically gave the dermatology rights to Kaken, and do that on a broader basis, to having a partnership that is a global partnership across multiple indications. Anything in terms of timelines? Obviously, is this something you want to have decided, obviously, before the FDA approval decision? Is that the kind of cut point we should think about at the far end? I think I've been asked this question a couple of times over the last couple of days. Fundamentally, the longer you wait, the more decisions you will have made that are not reversible. So the sooner you can get it done, the more the partners could actually then discuss how to best approach this. There's no set timeline per se. There have been situations where partnerships were done very late, but then you're not just basically trying to sell the molecule itself, but you're also going to sell the strategy, and I think that's the piece why earlier partnering makes more sense. Okay, got it. Maybe just provide us kind of an update on the rest of the pipeline. I know you guys have more things going on beyond envu, obviously, that was the major focus, but just what's the latest on the rest of the pipeline? Yeah. So for A5, we originally had disclosed that we would take it into MS. After further evaluating the situation, especially in relapsing remitting MS, we realized that for us as a company, that would've been an indication we could have pursued at least a phase II in, but that was hard to pursue at this point in time. When you look at primary and secondary progressive MS, they are a lot harder, a lot longer, and something that will be hard to take all the way to the market. So we decided, based on the market assessment and some internal data, where we actually have identified a biomarker for Parkinson's, that we are switching to Parkinson's. So we are finalizing the design of our Parkinson's study, and plan on basically initiating a phase II-A biomarker study in Parkinson's in 2027. Then we have an earlier pipeline, where we intend to put an additional molecule into the clinic next year. Can you tell us anything about that biomarker at this point? The biomarker for Parkinson's? Yeah. Anything you can elaborate on yet? Yeah. Basically, it's a biomarker that we discovered is highly associated with Parkinson's, and it turns out that actually TYK2 modulates that biomarker. We're now, as part of this study, looking a little bit to answer the chicken and egg question. Is this a biomarker that is just basically running in parallel, or is there any predictive value in it? Then we're looking at other biomarkers, and I'll let Jörn a little bit allude to how we think about the overall Parkinson's study. Yes. The study has a couple of goals. First of all, we want to study how A5 basically engages its targets, both in the peripheral blood but also in the CSF, so there will be LPs as part of the study. That's the first goal. The second one is the treatment with A5 able to down-modulate certain biomarkers that are associated with the disease? So markers of neuronal destruction, will those come down or at least not come up as they typically do during the progression of this disease? It's not primarily a study that's directed at clinical outcomes. Those studies can be quite long and require much larger numbers. We may get some hints perhaps about clinical outcomes, but it's primarily a study that will inform and potentially de-risk future studies that are directed at clinical outcomes. Last question, it was just on the cash position burn. Just maybe remind us where we stand in terms of guidance on that front. Yeah. We haven't changed the guidance yet. Originally, our guidance at the end of June was that we have cash through or into the fourth quarter of 2027. That assumed that we would do all the lupus and psoriasis activity and prepare the other trials for A5 and Sjögren's and CLE, plus our research pipeline. We're certainly reviewing exactly how we move forward, but we still have more than As of the end of June, we had more than $500 million in cash. We want to make sure we're very judicious with the cash, but a lot of it certainly goes towards psoriasis and preparing that market. Then I think whether there's a partnership or other ways to fund the company will define ultimately what above and beyond our base case plan do we do. The next couple of months certainly are critical for us to make some of those decisions. But I think the most important thing is that we think about what do we do and how do we optimize the outcome with the cash we have on hand, and what are additional ways to maybe strengthen the balance sheet. There's everything on the table, and with partnerships certainly being a key focus. Yeah. Great. Well, thank you so much, guys. Really appreciate the time this morning, and best of luck. Thank you. Thank you. Thank you.