All right. Good afternoon, everyone. Welcome to Guggenheim Healthcare Innovation Conference. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. It is my pleasure to welcome our next presenting company, Alumis. From the company, we will be chatting here with two executives. We have the President and Chief Executive Officer, Martin Babler, here. And we also have Chief Financial Officer, John Schroer, here. Martin and John, thank you so much for your time. We appreciate you coming in. Martin, there is a pivotal moment coming for the company, right, and also for the TYK2 space with competitor data and your data coming relatively soon. Why do not you maybe spend five-ish minutes, give us sort of a highlight, touch on some of the key points, talk about some of the milestones, and then we go into the Q&A, if that is OK. Great. Yatin, thank you. First of all, thanks for having us. We certainly appreciate being able to tell you a little bit about the story. We are a company that is about four and a half years old, soon to be five years old. Our lead asset is Envutuzitinib, a TYK2 inhibitor. We entered that class not because it was a class that was a lot going on, but because we did a lot of genomic analysis. TYK2 is actually very rich on the genomic side. What we found is that TYK2 has the ability to really have a profound impact on autoimmune diseases when you have certain mutations, but also does that in one specific mutation where it just affects the kinase's function by doing it without having a phenotype associated with it. We developed two TYK2 molecules, one acquired, one developed in-house. One is a brain penetrant, that's A-005, and Envutuzitinib, the lead molecule I just talked about. Beyond that, we have Lonigutamab that came to us with the merger from Accelerin. We have an in-house pipeline behind that that we developed. We're a company with three clinical assets, all of them beyond phase I in phase II or phase III. The lead indication is psoriasis. As you just mentioned, for Envutuzitinib, the psoriasis program will read out early Q1 of next year. We're very much looking forward to that because I think it will show that TYK2 can be very competitive in the psoriasis market. We have that conviction because of our preclinical data, our genomic data, but also our phase two data. Behind that, Envutuzitinib, we are studying in lupus. That will read out for a phase IIb that is designed as a pivotal trial, will actually be in the third quarter of next year. Those are probably the two key data points we have next year. Got it. At the same time, next year, we will also have quite a few external factors that will influence our business. There are going to be quite a few readouts in the TYK2 space from our competitors. We will also see how oral psoriasis drugs will do in the market if they are launched properly. Ultimately, I think the other piece to keep in mind is that we are planning to ultimately partner our asset, at least Envutuzitinib, that could have an impact also overall on how the company is going to be. The company has executed very strongly over the last 12 months. We are looking forward to meeting these milestones in the coming year. A year from now, we will really know who we are as a company. Very good. Thank you for that overview. Perhaps before we go into the phase III program, the onward program, could you put in perspective what you have generated with Envutuzitinib in phase II in psoriasis? How does the profile look, whether it is within the TYK2 class or also the emerging IL-23 class? Then we go into the phase III discussion, your expectation, and all of that. Yeah. TIYK2 inhibits both interferon and IL-23 and probably has some additional effects on some other cell types that we are not all discussing as much. Fundamentally, when we started the program, the intent was to show that TIYK2 can really have an impact on some of those diseases. When we compare our molecule with others, I think the key element is with those that have come before us in the U.S. here is that we were the only ones who did not have to dose-reduce as we moved from phase I to phase II. That was because we had a cleaner profile. The other molecules all had issues in terms of tolerability and in some cases, maybe even tolerability/safety. It forced them all to dose-reduce. Our preclinical data and our genomic data really suggested that how hard you inhibit a target mattered in TYK2 in the clinic. We ultimately proved that out in our phase II, where we had a very clear dose response. The harder you hit the target, the better outcome you have. I think the biggest distinguishing factor between our molecule and others is that we can actually dose-increase all the way to where we have maximum target inhibition. When you dose-reduce, by definition, you basically cannot go to that maximum inhibition without bringing in additional liabilities. That is really the distinguishing factor for our TYK2 versus other TYK2s. When you look at our phase II data, when you look at PASI 75 in the long term, PASI 90 in the long term, that is a data set that has not been accomplished by other molecules to date. Ultimately, we believe it's going to be very competitive in the psoriasis space. Got it. Got it. So the phase II phase III onward program enrolled pretty fast. I think you have over-enrolled it. Can you just tell us what led to the over-enrollment? Was the excitement around the target, or is generally the psoriasis studies go fast? When you read out, what exactly should we be focusing on in terms of the efficacy, whether we look at PASI 75 or PGA 0/1? Yeah. I think the enrollment partially has to do with the simplicity of the molecule. I actually believe we are underestimating how dermatologists like simplicity because the molecule does not require a lot of hand-holding. It does not require a lot of explanation. One of the things we hear from physicians that have used it, investigators that have used it, basically, they say, you know, it is a drug that really is very safe. It works. It does not require any fasting or anything. I think the simplicity actually has helped us with the enrollment. The trial is relatively easy as well. We clearly enrolled this trial very fast. We actually also, our phase II was enrolled faster than any of the competitive phase II molecules. We believe partially it is just the simplicity, the ease, and people actually like the molecule. Ultimately, we did over-enroll because we enrolled so fast towards the end that we could not stop it in time, if you so want. That was a really great outcome for us. It helped us to do exactly what we had originally planned. When we started our TYK2 program, we were about 18 months behind the competition. We always told people, well, we are going to be reading out our phase III about the same time as everybody else. People always laughed. That is actually exactly where we are going to be. We are going to be very close. It might be a few months behind, but still very close to where the competition is. I think it is partially because of the execution of the team. The other part is also because what we hear from physicians and especially from these investigators, they actually like to handle this molecule. I do believe that ultimately could also translate into the commercial market. Got it. Actually, before I ask you about the expectations, are there any features of the study that were, or what are the key differences between phase II and phase III? Because the studies are fully enrolled, could you just talk about high level, the demographic, how many bioexperienced patients we should expect, any difference from phase II? Yeah. So we haven't really shared the demographics yet. But what I can tell you is that in the phase II, the phase II was a U.S. and Canada mostly focused study. One of the things we should expect, and it had actually one of the highest BMIs in the phase II of any studies that have been performed in psoriasis recently. It's not surprising if you have Canadians and Americans mostly in the study. As you go from a rather regional study to a global study, I think the demographics are going to be a lot more similar to other studies than different. What we are probably going to see is a little bit less BMI, just based on the fact that we went to a global scale. Other than that, we did have a larger bioexperienced patient population in our phase II. We had a higher BMI. We had longer duration of disease. I believe, or we believe, that that will be somewhat neutralized once you go global. That is only to our advantage. We did not, in contrast to many of our competitors, change the dose or change any of the administration. That should all be consistent. That is why we believe we actually have a pretty good chance to just repeat what we've seen in the phase II and the phase III. Got it. And then one of the studies has, so you picked Otezla as a competitor. You could have picked TYK2. Just why that's the case, or what was the thinking behind? Yeah. First of all, we did this, made this decision at the time where we did not know whether TYK2 is going to be a really relevant drug in this market. I think actually our assertion that it might not be the most relevant drug in the market. The other one was that the availability of Otezla in markets around the globe was actually a lot easier for us than it was for TYK2. That also influenced our decision. We always said, if we believe we need a head-to-head of Otezla against TYK2, then we can always do that as a follow-on study. That still is something that we are considering. At the same time, though, Otezla really presented itself as probably a better comparator because we did it mostly not because we needed to prove that we are better than Otezla. I think that will be pretty evident. We did it because we wanted a comparator at six months. We originally actually went to the FDA and tried to convince them with a creative design to have six months of placebo, at least in some patients. That was just a non-starter with the agency. That basically meant we needed an active comparator in the first place. The study that you're going to read out is six months, right? Six-month readout is what? The readout in a couple of months in early Q1 will actually be the 16- and the 24-week data. 16 and 24-week. Yes, absolutely. OK. And then again, are you just trying to replicate, or is there a particular delta over TYK2 you are targeting for? Just curious, like on these various endpoints, whether it's PASI 75, 90, or PGA 0/1, why should we think about it? Yeah. If you look at what people really look at as success these days, there are different factors. We do believe that if we can replicate what we've seen in the phase II of between week 24 and 52 in terms of PASI 90, between 60-70%, that makes for a very highly competitive product. Yeah, there are actually other profiles that could still be successful. We do believe that for the highly successful, if you're in that 60-70% range between week 24 and 52, that probably is one of the things that we're happy to say that that would make for a really successful product. That's PASI 90? Yeah. OK. OK. How quickly you will be able to file NDA? Will it be like later this year? Sorry, not this year, 2026 or 2027? We have not yet declared that. The one piece that I do share with folks and make sure that everybody understands is that because we ran the phase III the way we ran it, we do have still some data we are collecting in terms of durability and basically maintenance. We have still to collect some of that data. We can file next year. We will be more precise once we have the data in hand on what that looks like. OK. Very good. Moving on to the next indication, SLE, lupus. There is a lot going on in the space. I think on the oral side still is a pretty wide space. Talk about the mechanism. Talk about what you are doing in the study. I mean, we have seen some data from Bristol in this disease. Love to understand a little bit more about the lupus opportunity you study and the expectations. Yeah. Lupus actually is really interesting because I think a lot of people did not necessarily realize how much validation we already have. We know from the genomic data that lupus actually is one of the diseases where there is a lot of protective effect if you have that 1104 mutation in TYK2. And about 5% of the Caucasian population, a little bit less of others, have that. The other validation that we have is, of course, the TYK2 data in lupus. Then the third one is anifrolumab is a very successful drug at this point in time. It has a run rate that approaches $1 billion now. Basically, that is going after the interferon pathway. We are doing the same thing. We are actually, if you think about it to a certain degree, an oral version of anifrolumab plus some additional benefits, if you so want. In our minds, that's a lot of validation. The other piece in lupus that is absolutely critical is that you actually develop a trial and you perform your trial to minimize the placebo rate. We were fortunate enough that our CMO is actually the person who developed anifrolumab and has a lot of experience on how to avoid a high placebo rate. We have implemented all those learnings in our own study and added some additional pieces to really make sure that we get the placebo rate relatively low. We hope through all of that, we have a pretty good understanding what an efficacy rate could look like and at the same time reducing the placebo rate. Overall, therefore, hope to have a positive outcome in that trial. Got it. How big is the LUMA study that you're running? When exactly are the data coming? The study is a study with over 400 patients. We're starting three doses and the placebo arm. It's about 100 patients per arm. We completed enrollment in July of this year. It's a 48-week endpoint. The third quarter of next year is when we expect to have the data for that study. Would you report both on BICLA and SRI-4, or is, yeah, I think the primary is BICLA? The primary is BICLA. That's correct. And then the secondary is SRI-4. SRI. Any good benchmark for us to look at BICLA? Like what is a good data here? I don't know whether there's a good comparator at this point for that. I think we'll just have to look at the data itself and then think about how to best put that in perspective. Then the path forward will be after this, you have to run a pair of phase III studies, or? This trial, because it's a significant trial, is actually designed and performed as a pivotal trial. That could potentially enable us to only have to do one phase III trial. We will go to the agency afterwards. We already had communications with the agency at the time of the start of the trial to really design it so that it could be serving as a pivotal trial. It's possible that we would only need one additional trial. Based on the enrollment rate we had with this trial, again, where people really liked the drug, we do believe that if we only had one trial, that could be something that could really help us accelerate the whole process. Got it. Anything on the competition front in SLE that's going to read out the Bristol program? Do we know if? Yeah. So there's two readouts for TYK2 in the next 12 months. One is the BMS phase III will read out. And then the other one is Galapagos will have a small lupus trial. We don't know yet what to make out of that one because there's a recent poster from Galapagos that shows that their target inhibition levels are just slightly above TYK2. So we just don't know whether it's enough inhibition of the target. And it's a relatively small trial. But if that trial reads out positive, I think it's just supportive of what could possibly happen in lupus. Got it. Other indications you are thinking about that we should be focusing on for TYK2s? When or if this lupus trial is successful, I think that will open up a lot in terms of interferon-driven indications. And we certainly are interested in Sjögren's disease and others there. On the IL-23 side, the key question is the question about IBD. And what does TYK2 do in IBD? We will have answers to that question likely next summer because of our competitor, Salzitnib, actually running two trials in ulcerative colitis and Crohn's respectively. We do believe that there's an opportunity, especially for combination in IBD, whether we want to tackle this ourselves or in collaboration with a partner is TBD. Got it. Got it. All right. Moving on to A-005, the brain penetrant, right? I think there is just a lot of interest in finding novel targets that can access the brain. Where are you with this molecule? How does it compare to some of the other stuff that we are seeing on the BTK? Because you sort of pioneered that at your previous company. What are the timelines for you to move into the clinic? That program is in the clinic. Phase I is completed. At this point, we also have completed all the other requirements that would enable us to really do a strong phase II. The idea is that we start with MS. That would happen in the first half of next year. That program basically would be a three-month study like we've done with tolebrutinib, where you just do basically a reduction in lesion. Then possibly an extension to that to really understand the rest. The best way I can describe it to you, and we'll have to look at what the data from evobrutinib look like right now. In our minds, the BTK inhibitors are really great at reducing disability, but maybe not as good as others in reducing inflammation and therefore relapse rates. We'll have to look at that. In our minds, this is really a BTK plus kind of approach because the anti-inflammatory component of TYK2 is stronger than it is with a BTK inhibitor. We will have to see. The other interesting aspect, though, is that we have a very profound effect on microglia. A lot of the inflammatory components of degenerative diseases could also be very attractive, including Parkinson's or MS, Alzheimer's, et cetera. Do you stay with RMS, or could there be a sort of a different type of MS population, whether it's BPMS or non-relapsing? The biggest unmet need is clearly in the progressive population. When we started this program, we even thought about could you actually combine a BTK inhibitor and a TYK2 inhibitor to really make a difference? Because even with the data we have today in the progressive population, you get to 20%-30%. You do not get higher than that. If you look at the same situation like in ulcerative colitis and Crohn's, where hopefully combinations are ultimately going to help these patients potentiate the effect. OK. Maybe just quickly on Lonigutamab, what is the path forward there? Are you still sort of doing the evaluation? Yeah. Loni is a, let me put it this way. We believe Loni is a drug. The question is, where do you study this drug and how you best develop it? We have some additional findings that we believe are very interesting. We want to verify some of those and then decide whether this is something we're doing by ourselves, whether we do this in a partnership, or how do we best move forward. I think there is, or we believe strongly that there's value in this asset. The question is, how do you realize that value? We have a lot of readouts from competitive mechanisms, competitive programs over the next couple of months. We believe that that can help us also really well define what you do with lonigutamab. Got it. Thank you, Martin. John, question for you. How is the financial health of the company? How's the balance sheet? What's the burn rate? The balance sheet is strong. We ended the second quarter with more than $480 million. At that time, we had guided that provides us cash runway of operations into 2027. We will be reporting our third quarter in the next week, by the end of this week. We will provide an update at that time. I do not anticipate any surprises. Got it. Very good. Very good, gentlemen. Thank you so much for your time. Thank you. Thank you.