Great. Thank you so much, everyone, for joining us for one of the last sessions of the conference today. I'm Terence Flynn, the U.S. biopharma analyst here at Morgan Stanley, and very pleased to be hosting Alumis this afternoon. We have Martin Babler, who's the company's President and CEO, and John Schroer, who's the company's CFO. Lastly, 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. Thank you both so much for being here. Really appreciate the time today. It's great to see you. I thought maybe if you could just share a high-level overview in terms of the company, just to level set in terms of where you stand with the pipeline and kind of strategic priorities right now. I know we'll dig into a lot of that as we go through the Q2. Thanks for having us. We are a precision immunology company based in the Bay Area. We're about four years old. We have currently four key assets. The lead one is ESK-021, now called Envuducitinib or Envu. This is a TIK2 inhibitor that we're studying in psoriasis in a phase 3, and we're studying it in lupus in a phase 2. The psoriasis will read out in the early first quarter of next year, and the lupus study, the 2B study, will read out next summer in the third quarter. Behind that, we have a second TIK2 that is actually a brain-penetrant TIK2 that has shown in phase 1 that it's a 1:1 ratio between the blood and the brain. It's the first and best-in-class asset at this point in time. Both of those, for us, basically are pipeline assets that we believe could be a pipeline in a pill. Behind that, we have lenaludomab that came to us through the merger with Accelerin. We have an asset that is currently a preclinical asset that we're planning to put into the clinic shortly. We will have phase 1 data for that also next year. That's the company in overview. This is a company, when we say precision immunology, we spend a lot of time really data mining. We started as a data mining company, if you so want, originally. We do a lot of genomic analysis. That's actually where we got excited about TIK2. We have discovered in the meantime two biomarkers related to TIK2, one cyclic one that we've made public and that we use to see whether we could possibly predict responses. In psoriasis, we couldn't because the non-responders were actually too few to find that out. We certainly will look at that in lupus. We discovered another biomarker for a CNS indication for Parkinson's that is related to TIK2 as well. Overall, a company that basically has two key assets in the TIK2 space and broadening now around that and beyond that, and a company that has near-term readouts with two molecules that could be a pipeline in a pill and basically what we consider best-in-class assets. Great. Thank you so much for framing that for us. I guess first, as you mentioned, the kind of lead programs are focused on TIK2. I know there's a lot of attractive biology here. As you thought about pursuing this target, maybe just remind us what it was about TIK2 that you decided to center on this as your lead target. Yeah, that's a really great question because what we've actually been able to do is now show that what we found genomically has translated into the clinic. One of the most fascinating things about TIK2 is that it's actually genomically quite rich. There are quite a few mutations, and there's one that really stands out for us, which is the P1104A mutation. That mutation specifically downregulates the kinase function of TIK2. It doesn't affect the scaffolding functions and other functions. What that mutation basically does is it exists in about 5% of the Caucasians and a little bit less in the general populations. Interestingly, that mutation actually has no phenotype. If you could really just downregulate TIK2 kinase function, you actually should have quite a safe drug. The other thing is that when you have this mutation, you actually are protected from many autoimmune diseases. In the case of lupus and psoriasis, the average protective rate is about 50%. You are 50% less likely to get any of these autoimmune diseases. Interestingly, when you actually look at the heterozygous versus the homozygous, the heterozygous have about a 20% to 30% protective effect. The homozygous, that protective effect actually goes up to 80%. The better you reduce the kinase function for TIK2, the better your protective effect is. For us, we wanted to see whether we could translate that into the clinic. From the get-go, for us, the level of inhibition of the target was a critical thing that we wanted to tackle. That's why, in our case, we have developed a molecule where we can get to maximum inhibition without having side effects that prevent us from doing that. So far, at least, this has been one of the only TIK2s where you did not have to dose reduce in phase 2, and you could get to that maximum inhibition. That's really the differentiating factor. In the clinic, then, that has led to about a 20% delta between the highest dose and the second highest dose in terms of efficacy. We believe that's very, very meaningful. Maybe talk to us about some of the CNS angle as well. I think you talked about the psoriasis, but how do you think about the CNS angle in targeting TIK2 there? Yeah, so interestingly, TIK2, in our minds, has really two opportunities in the brain. One is when we ran the EAE model for TIK2, we saw that it has probably one of the strongest anti-inflammatory effects that we've seen in any brain-penetrant compounds. We actually did beat the standard in that model, which is fingolimod so far. In the prophylactic model, you cannot even induce inflammation, actually, if you give our molecule at an appropriate dose. The other piece is that TIK2 actually affects both microglia and astrocytes. There is a cell component to it that is very interesting. For us, we have been involved in the development of tolebrutinib, and we know that affecting the microglia there had a really significant effect on disability. We do believe that this is basically a BTK+ kind of opportunity because you get the disability effect from the microglial side, and then you get the strong anti-inflammatory effect from the TIK2 side, basically. OK, great. Maybe before we dig into some of the data and the catalysts here, one big picture question for the field is just injectables versus orals for psoriasis and how to think about the paradigm on the forward. Maybe you could just give us your view, level set us in terms of where we stand right now and how this ultimately plays out given the evolving competitive landscape as well as you think about orals versus injectables and ultimately what the mix looks like in the forward. Yeah, this is a very interesting aspect because I think because the dollar share of the injectables is so high, most people don't realize that in psoriasis, actually, the biologics only have less than 10% of the patient share of the diagnosed patients in psoriasis. It turns out that the oral drugs have a higher patient share than the injectable drugs, at least today, in the psoriasis market. You would not assume that based on the dollar share of these molecules. What we know from that is that there still is actually an overall preference of patients to have an oral drug. We just haven't seen any high-efficacy oral. Our goal really was to develop a high-efficacy oral. When we saw this phase 2 data per se, we were not sure we could get there. Once we saw the long-term extension data, and we saw basically between 80% and 90% positive 75%, we saw between 60% and 70% positive 90%, and between 40% and around 40% positive 100%, we really felt that we're approaching now the levels that you can get with injectables. We really believe that that will change the entire paradigm. Given that we're not the only ones with an oral, I do believe that there will be enough noise out there in the market that we really shift that a little bit, where you might still see the thought leaders that get the tertiary patients. They will probably stick with the injectable. Your community dermatologist that can now offer an injectable versus an oral will likely do that. We believe that many patients will choose an oral because the delta now between the two has been narrowed down quite dramatically. OK, great. You mentioned you're running the phase 3 program for psoriasis right now for Envu. It's called Onward. You're going to have data in the early part of the first quarter of next year. Maybe you can just remind us kind of the design of that program and then set expectations here based on what you saw in phase 2. What would you characterize as kind of a win in the trial? What are you hoping to see? Yeah, so the design for our trial is such that we have a placebo-controlled portion of the trial that is over a four-month or basically 16-week section. We will basically show that data as part of the readout. The other part is that we have a 24-month active control section. In the early part of Q1, basically, our goal right now is to show both trial 16 and 24-week data. The 16-week placebo control, the 24-week active control data top line for both trials and the associated safety. The patients then roll over to a longer-term extension where they stay on drug. We will have the data out to 52 weeks later. The initial setup will be that way. For filing, we need a couple of patients that roll over in or 200 patients that roll over in that extension. They will go into basically a withdrawal portion that will give us the durability and will give us the maintenance data. That will be included in the filing so that in the label, what you will have, like with all other drugs, you will have 16-week placebo control data. You will have 24-week active control data in a table, likely. Then you will have in the text basically what the maintenance and the durability of the molecule is. Yeah. Just remind us on the PASI side. I mean, you mentioned these numbers, but it's worth highlighting again how to think about the PASI, primary endpoint 75, and then what you're hoping to see for the placebo, I guess, as well. Yeah, so basically in the phase 2, we saw that we had 64% placebo-adjusted PASI 75 at week 12. When you look at the data sets that are available to us today, we would argue that probably being between 50% and 60% at week 16 is competitive. We haven't seen yet what some of our competitors are doing there in a pure adult population. So far, at least for Johnson & Johnson, we've only seen a mixed population with adults and adolescents. The other TIK2 inhibitors have had readouts. The only one that had a 16-week readout today is basically Sotyktu, which was about 40%. We clearly believe we need to be above that by 10% plus, but 50% to 60% for that. The way that dermatologists describe these high-efficacy orals at AAD is that they assume for our drug and others that we will be in what they call this 80/60/40 paradigm, which is you're around 80% for PASI 75. Between week 24 and 52, you're about at 60% for PASI 90, and you're around 40% for PASI 100 in that period. We all know that PASI 75 stalls out, if you so want, a little faster than PASI 100. That might be delayed beyond where we can measure at 24 weeks. Our assumption is that's kind of the range that you want to be in, that we believe will be highly competitive and will really be classified as this high-efficacy oral drug. You are going to release data from both trials at the same time. That's the plan, yeah. OK, got it. You mentioned the differentiation versus TIK2 on efficacy. Just remind us on safety tolerability, how you're thinking about that, and setting expectations ahead of this data set as well. Yeah, the one differentiator, if you look at from the safety in the phase 2, that was probably the most outstanding differentiator was that we did not have those skin reactions that were associated with some of the other TIK2s. We believe that's probably more a kinase effect than it's a TIK2 effect. Our expectation will be that that is going to be the same, that we will see less of those. Also, we have not really seen any blood chemistry changes, which is one of the challenges for TIK2 currently because patients actually have to come back for a blood draw. We do not anticipate to have that blood draw in terms of safety. We really don't have seen any safety signal. At this point, we have more than 2,000 patients on the drug. Many of the early patients have been on the drug for more than a year and a half, two years now. We have long-term safety in quite a sizable population. We feel pretty good about the safety profile we have today with the molecule. OK, great. You know, we mentioned the differentiation versus Sotyktu. I think there's also a focus on some upcoming data for Takeda and their TIK2 inhibitor. We're going to get some phase 3 data later this year. Johnson & Johnson already has phase 3 data for their oral IL-23. Maybe just help us think through the differentiation versus those two assets, one more on the TIK2 side and then one on the oral IL-23 side. Yeah, we've always made a point about how we believe that the level of target inhibition is critical. I think our hypothesis actually has been confirmed by the data for some other earlier TIK2 assets that are still early in development. There were two phase 2 out of China that showed molecules that had better inhibition actually had better outcomes. There's also a second molecule that Bristol Myers Squibb had that has been licensed now by Bain and a couple of others that has a data set that we believe could possibly also support that theory. In our minds, the key question really is, how does pharmacology translate? There are two aspects to that. One is that we believe that hitting the target harder is better, and we believe that we actually have a molecule that hits the target really hard. The other one is also the variability that you see in psoriasis studies. As you know, you look at some of the even injectable trials, sometimes the same trial divided into two sections, these sections actually have quite some variability in it. I think we have to be a little bit cautious. We don't know yet what happens, but if pharmacology really works its way through, we do believe that there's a chance that we see improvement over Sotyktu, but maybe not exactly the same as we see. The data from Johnson & Johnson is interesting because to date, we actually have not seen a pure adult patient set. All we have seen to date is data sets that are mixed with adolescents or only adolescents. We will see some data sets with adults only in the coming weeks, and it will be interesting to see whether that holds up or whether that has a slight effect on efficacy. We do believe that all these drugs are competitors. We do believe that they all are viable oral drugs, and the question just is how do they stack up with each other? We also believe that there is a market for more than one here because people will not stay forever on one drug, and there is going to be nuances. One of the interesting things that we've seen in our data set to date, at least, is that when it comes to certain subtypes, we actually see TIK2 may be more beneficial. One aspect that is really interesting in psoriasis is that when you ask patients, what is the number one symptom that you would like to have some resolution for, they will tell you it's itch. The interesting thing in psoriasis, itch in psoriasis doesn't come from the disease itself. It comes from the disruption, from the mechanical disruption of the plaque. For physicians, it's not necessarily an issue because they say, just don't rub yourself. For the patients, that's different. We've actually seen really fast and deep resolution of itch, which we believe TIK2 might actually be available to address better than other mechanisms. The other subtypes, we will have to see what the data looks like. We know that IL-23 is not as effective as other therapies in plantar disease. Your foot and hands might actually see less resolution. We do believe that there's also going to be that aspect. There are going to be preferences. I think the most important other aspect is really in terms of simplicity of prescribing that will play a role in the market as well. Can I just go back to the comment on the adolescents? I haven't looked at the data as closely. Is the implication that adolescents are more responsive to therapies, and so you have higher PASI rates in those versus adults? I'm just not as close to the. Yeah, I think that's a really important aspect that we need to all be aware of because we know people will compare across trials. There are three areas where you will see a difference in terms of response. One is basically disease duration. The other one is disease onset age. The other one is actually BMI. As you think about comparing across these trials, you have to keep that in mind. When you look at the data that Johnson & Johnson has presented on the adolescents only versus the combined set, the adolescents did fare a lot better than the combined set. The question then becomes, if you take the adolescents out, how do the adults only look? I think that data set, basically just on math and statistics, probably is slightly lower than what we've seen so far. At least in that trial, it would be. It's going to be interesting to see whether that is also true or whether it just holds up. That's an interesting one. The other one is I think we need to all look at the demographics of the patients that have been studied. If you have a BMI of 24, that is a very different outcome than if you have a BMI of 32. I think that those are elements that we believe people need to factor in as they look across different trials and what the outcome is. OK, great. I guess just as we pivot to maybe more of the kind of strategic commercial questions here, what's the latest thinking on partnering? Obviously, there's a key value inflection point coming up here with the phase 3 data. How are you guys thinking about that as a potential opportunity? There are two aspects to that and they're really strategic. The first one is the likelihood that we will launch a molecule with this much opportunity on a global level by ourselves is very, very low. We've already did a partnership in Japan. We strategically specifically did that so we can still do a global deal. In our minds, this is going to be a really interesting process to look at. We always felt like we want to make sure that we can get the appropriate value for the asset and certainly have had conversations with most people about what happens after the data is out. The second aspect of that, though, is really important for us. That is that with where we are currently with our balance sheet, we're actually able to possibly make that decision not necessarily just after the psoriasis data, but wait to make that decision after the lupus data. If we feel like we have conversations, but we're not getting the value we want for the psoriasis-only asset or the combined asset at the time, we could theoretically wait until we have the lupus data and then make a strategic decision what is the best way forward. That's a luxury we got with this merger that we believe is really important from a strategic standpoint. OK, makes sense. The QD formulation, remind us the timelines there. I know you're kind of working in parallel on that. I imagine that's another important aspect of the value of the asset. It is. We actually do have a formulation. The way that we share it with folks is that we know what the formulation looks like. We actually have more than one. Our goal remains that we will have the QD formulation at the latest within one year of launch. The reason for that really is that if you do a bioequivalent study, that's one way to do it. The other one would be to do a clinical study. If you do a clinical study, we have to wait for the submission until the NDA is approved to file an SNDA. The interesting aspect about this, and I think I've now explained this to people because people hadn't thought about it necessarily this way, is that the FDA for bioequivalents is really looking at CMAX and AUC. For us, we know from our data set that CMIN and being above IC90 is so critical that we optimize a lot more for AUC and CMIN than we optimize for CMAX. What it basically means, if we want to satisfy the FDA and satisfy us, is we basically have to optimize for all three. We're still trying to see whether with the formulation we have, we want to do any tweaks to it that could possibly do that. Our goal remains to have what we always said, which is we will have a once-a-day within the latest one year of launch. OK, great. One other question we get frequently is just, you know, as we look at the Sotyktu launch, I think it's underperformed expectations. Is there anything that you guys can learn from that as you think about a potential launch of Envu here going forward? What would some of those things that you could leverage be? Yeah, I think we can actually learn a lot. I think it's a really interesting case study because we believe, from our analysis at least, that there was, and you hear that actually from dermatologists repeating it back to you, it was a little bit of an overpromise and under-deliver because originally the molecule was positioned as competitive with Skyrizi. It was priced like Skyrizi, and ultimately, it just didn't meet the expectations. When you switch it over and now you compete in the oral space against Otezla, it's just harder because now you've priced it in a different place, et cetera, et cetera. We do believe the trick with Sotyktu was a little bit that it was basically not competitive with one positioning and then not competitive with the other positioning. That's always a very hard place to be. What we've done is a lot of work around what actually would our pricing strategy have to be based on where we position it, how do we best position it, et cetera, et cetera. I do believe that this is not a target-related issue, but this is more likely a molecule and strategy-related issue. I think that's a really important point to make because I think too many people believe, well, it's the target. If you have a highly efficacious molecule, you have a different outcome. One of the encouraging things for us is when we actually talk today to dermatologists that have used our drug in clinical trials and have used Sotyktu, they will tell you that this drug feels different. They really have a different sense of what that drug can do. I think that's an important aspect to just factor in. Ultimately, it comes back to a very important piece in terms of what, no matter what your strategy is, simplicity of prescribing this drug in the dermatology market is absolutely critical. OK. We'll stay tuned in terms of the strategy because I know you won't tell us the price right now because you have the profile. As you think about it, let me actually just on that point, I do want to point out something that I think people sometimes don't realize because we're not expressly necessarily saying it. We, because we have two TIK2s and we have multiple formulations, have more degrees of freedom in terms of pricing than our competitors have. We also do not have an incumbent molecule already in the market that we have to think about as we price our drug. I do believe having more degrees of freedom gives us a little bit more flexibility on how we price and how we launch and how our commercial strategy is handing out. OK, great. You alluded to some of this in terms of the other indications for Envu here. You talked about lupus. I know IBD is another one that we often get a lot of questions on with respect to what other oral options are coming for IBD patients. Maybe talk to us about your conviction level in lupus because historically, that has been a very challenging therapeutic area to develop drugs for. Number two is IBD, et cetera. What does the opportunity set look like beyond even lupus as you look forward? Yeah, so for lupus, our conviction is very high. There are two factors to that. The first one is, is this target the right target for lupus? We have now two successful lupus trials with two different mechanisms that are focused on interferon. One is the BiGen data. The other one is anifrolumab from AZ. They both point to actually interferon inhibition as a key way to help lupus patients. That's exactly what we do. We basically know from our phase 1 and phase 2 in psoriasis patients at least that we downregulate the interferon level to a normal level, and we have a strong suppression of that pathway. That's one. The other one is that our competitor basically has already shown positive data on lupus. The third one is actually that when you look at this 1104 mutation that I started up front with, the protective effect in lupus is as strong as it is in psoriasis. It's almost 50%. We really believe that that validates the target quite a bit. The other piece for lupus is you have to really think about how you minimize your placebo effect in the trial. We're fortunate that we have our CMO, Jeroen Dropper, being a lupologist all his life and run several successful trials with anifrolumab. He has been there, but he's also had a few failures. He has done a lot of analysis of what we need to do. We believe the most important ones are enroll the right patients, make sure that the comeds are really closely managed, and the third one is really make sure that the sites and the investigators really know the tools. We're also controlling that by crawling over the data as it comes in all the time to see whether there's any discrepancies in the data. That is a big level of conviction we have. Because we now have a program that goes after the interferon side of things and one that goes after IL-23, by next summer, when we have these two really transforming readouts, we will also really understand where we want to focus as a company, more on the interferon side or the IL-23 side. IBD, in our mind, is a really interesting aspect for TIK2 because we basically looked at the genomic data in IBD. One of the most fascinating things about IBD is that actually the heterozygous carriers of the mutation have almost no protective effect, but the homozygous have 80% protective effect like others. In psoriasis or lupus, it goes from about 30% protective effect to 80% to 90%. In IBD, it goes from 0% to about 80%, which tells you that in IBD, probably the level of inhibition of the target is even more important than in all the other indications. We're looking forward to see some data down the road. We do believe there is a possibility there. The evidence is not quite as strong as for lupus. There's clearly something, if you suppress the target really well, you should see a benefit. There are two ways to go about this. One is maximum inhibition. The other one would be a combination approach as well. OK, maybe I'll come back to A-005 here. John, you could talk about just, you know, OpEx through this year into next year, kind of strength of balance sheet and where you stand. You know, how far does that get you through the catalyst path that Martin's talked about? Thank you. At the end of the second quarter, we ended with $486 million of cash and cash equivalents. For the cadence of spend throughout 2025, we've also guided in our most recent release that the activity level will decrease on operating expense significantly in Q3 and Q4 over what we've experienced in Q1 and Q2. That's just a natural decrease in activities around the trials now that we fully enrolled the psoriasis program. With the cash that we end the year with, it is currently projected that we will have cash runway into 2027. You can get past those key inflection points. Yep, that is correct. We'll get through the early Q1 readout for psoriasis phase 3s and also the Q3 phase 2b for lupus. OK, great. Now, maybe just pivoting to A-005, which is the oral CNS-penetrant TIK2. We talked about this a little bit at the beginning here. Maybe just level set us in terms of that phase 2 trial start. I think it was pushed into first half of 2026 in conjunction with second quarter earnings. Just remind us kind of why that was. Any thoughts you can share at this point about design of that trial and endpoints, et cetera. Yeah, let me start by saying this is not a prioritization exercise or anything. This was literally a resource issue because remember, originally, we planned to have the psoriasis data in the second quarter. Now, we moved it from there into early Q1. We were able to do that because we just got so many patients into the lupus trial. We actually needed all the clinical resources to help us focus on that. Not only that, we also want to read it out fast. This was purely a resource issue on the clinical side. We pushed it from late this year into the first half of next year. We will have, to start that trial, the chronic tox done, which is important because that allows us to run a long-term extension potentially on that trial. The trial that we're planning to execute is an MS three-month imaging study. That's been done a few times now, maybe not quite enough times to be very clear how that imaging translates into ultimately the clinical outcome in phase 3, but enough times to know that if you hit a certain bar, you should have a good outcome. For us, that bar is probably in the 80%+ range for the reduction in lesions at three months. If we do a long-term extension to that study, then we have the chance to also have some data eventually, excuse me, on basically not just the lesion, but on relapse rate. The other aspect that we believe is very interesting is really seeing down the road, eventually, disability rate. How that translates, we don't know yet. Mechanistically, as I explained, we do believe that's really interesting in MS. The other indications would basically be neurodegenerative indications where we believe that it's now becoming clearer and clearer that the inflammatory aspect of those is very important. Having found now a biomarker, at least for Parkinson's, and having an ability to understand how that gets affected, we believe is important. Alzheimer would be another one. Ultimately, the fastest way to get to a clear dose with this molecule is by doing an imaging study for three months. OK, understood. Would that enable you to have proof of concept data by the first half of 2027? Do you think that's reasonable given the potential size of that trial enrollment timelines? That is. Look, from our standpoint, we did the exact same trial as tolerabutinib, and we were able to do that in less than a year. We believe even in today's environment, that's still feasible. OK. In the last minute, anything you want to leave us with on the rest of the pipeline, notable that we should focus on? Yeah, so the other thing we switched is that we are going to put another molecule into the clinic. It's going to be a new target or a different target. What we shifted is from basically saying we're putting it into the clinic is we will have phase 1 next year. The reason why we decided no longer to disclose the target is really because we want to, for competitive reasons, keep that under wraps. We're very excited about that and continue to really develop a strong pipeline. I think the only other piece I really want to mention is that we have lenaludomab that we got from the Accelerin merger. We do believe that lenaludomab has a differentiated mechanism. The question then is, how do you best translate that into a real benefit for patients? We're still evaluating that. We'll basically share once we know exactly how to move forward what we're going to do there. Great. Thank you so much. Really appreciate it. Martin, John, appreciate the time. I'll ask you to catch up. Thank you. Thanks for having us. Thank you.