Great. Good afternoon, everyone. Welcome to TD Cowen's I&I Summit. My name is Tyler Van Buren, Senior Biotech Analyst here at TD Cowen. It's a sincere pleasure to be joined by the Apogee Management Team here. From Apogee, we have Michael Henderson, the CEO; Carl Dambkowski, the CMO; Jeff Hartness, the CCO; and Jane Pritchett Henderson, the Chief Financial Officer. It's a privilege again to have the Apogee team. Thank you for joining us. Since we have 20-plus minutes and a lot to discuss, we're going to get straight into it. You guys, ever since you went public, have done a really great job of accelerating your timelines. I feel like every earnings report, I look forward to moving something up in our milestones table. A lot going on over the course of the first half of next, and then even in the second half. Maybe we'll just knock off each catalyst one by one. I wanted to start with the APG777 asthma data in Q1, right? Ebglyss did not succeed in asthma. Maybe you guys could start by discussing why Ebglyss did not succeed, why you guys might succeed, and what do you need to show with that phase 1 readout to have confidence that you are doing something much different than Ebglyss and perhaps similar to Dupixent? Yeah, I appreciate the question. This is one that we're spending a lot of time on, given that it's coming in Q1, and Q1 will be here very soon, especially just with how quickly the year is going at this point. I'll start kind of briefly with what we think Ebglyss did wrong and what we learned from kind of that historical trial back when it was in Genentech's hands. I will then hand it to Carl to talk through what we view as success for the upcoming phase 1 readout. Two things. First, it was underdosed. When you look back at those doses, it was about 20% of what the eventual effective atopic derm doses were. A far cry from what was found to later on be necessary to drive efficacy in atopic derm. The second is, even at that low dose, there were signs of efficacy in type 2 patient populations. Doopie came along, and they identified that you needed to have some type 2 disease, i.e., high eosinophils, if a type 2 drug was going to drive impact. We think by fixing the dose and enrolling a similar population to what Doopie later did, we can show we can be Doopie-like. Carl, do you want to kind of show or talk through what that means? Yeah. In this first study, we're looking at FeNO in asthma patients, and we're trying to enhance them for TH2-ness, essentially. We're doing that through high FeNO. It's a pretty good correlation with high eos. It's just a little less variable. We'd expect them to all be high eos or high FeNO patients here. We're looking at two things here. One is the comparative point, which is we want to see a magnitude of change in FeNO that is similar to Dupixent, which has been in the range of kind of 15-20 parts per billion. That contrasts with what Ebglyss has seen in their study, which was kind of 8-12 parts per billion. I think 10 parts per billion would not be as exciting, and we might be thinking something different. 15-20 parts per billion is putting us in the more Dupixent range. That is very similar to what Tezspire saw in their FeNO changes as well, too. As we are trying to make sure that we are differentiating too, the other piece we want to see is the change, sorry, the durability of that change. That change over a 12-week period as well to enable every three-month dosing, if not less frequently, too. Excited for that in Q1. Okay. Great. Thanks for that. Have you guys disclosed the dose that you're exploring in that phase 1 trial and how that relates to what you've disclosed with part A in atopic derm? Yeah. So it's a loading dose. So it's 720 mg, the same as kind of what we give to start in the AD study. Okay. And just maybe remind everyone how that exposure compares to the labeled Ebglyss dose. Yep. So Ebglyss is at 500 mg. It's kind of their day-one dose. So over 40% step-up on day one. Okay. Great. If you all achieve that goal or exceed that bar that you all just discussed, what are the future plans in asthma, and how soon can the next study start? This would show us that we have that same pipeline and product potential that Dupixent has and kind of unlocks our ability to think through asthma, EoE, COPD, kind of that full range. What Dupixent did is they ran phase 2Bs in each therapeutic area, so derm, respiratory, and GI, and that enabled direct-to-phase 3 studies for about a dozen indications and counting at this point for Dupixent. We would look to get a phase 2B going in asthma and a phase 2B in EoE. We would gate that, though, on needing to know what our fully optimized dose is in atopic derm, which we'll find out in Q2 with the part B data. We chose asthma as the first expansion indication because there's an approximate 30% overlap between AD and asthma patients. It is an important patient and call point for us as well. That's a good point. Yeah. The overlaps and comorbidities with these types of drugs is obviously pretty unique relative to other therapeutic areas. Let's get into the atopic dermatitis phase 2 program. Obviously, you guys reported great part A results over the course of the summer. During the first quarter of next year, we will also receive the 52-week maintenance data that you guys pulled forward from prior timelines. Based upon that part A 16-week data that we received, how clearly should that translate to 52-week maintenance data? Ultimately, what is the bar for what we should hope to see on the various endpoints at 52 weeks? Yeah. Good question. On the right here, you can see the two bars representing the bar for kind of success in maintenance data. It is of patients that achieve EC75 at week 16, how many of those patients are still at EC75 or better by week 52? For Doopie, it was 72%. Similarly, the same question for IGA01, and it is about 53% maintained at that IGA01 response out to week 52. We have an every three-month dose of 360 mg and an every six-month dose at the same every six-month regimen at the same dose. We are able to see, are we able to meet or exceed what Doopie does by week 52? In addition, what we are excited about here is we are the first company to get maintenance data in atopic derm prior to starting phase 3 studies. What this allows us to do is not question, will we have an every three- and six-month maintenance arm in the phase 3? It is, we will, but what are the doses as informed by this readout that we take into that study? Our every three-month week flow is quite de-risked. We're always at or above Ebglyss exposures. Our every six-month is, over that time, very similar to Ebglyss exposures as well. We will be able to take this data, kind of dial in the exact range that we should take into the phase 3, greatly de-risking our eventual phase 3 data, label launch, etc. The other piece which we are curious about is Doopie, OOPA, Rinvoq, other agents. They all kind of plateau by week 12-16 during induction, whereas some of our curves, when we talk to docs, they point out that they have not quite plateaued. Is there the ability to get some additional efficacy over that week 16- 52 or not? If so, that's another point of differentiation that we could have over competition. Not needed to win, as we'll talk through market research and how excited docs are already, but something that physicians are curious to see as well. Yep. I understand that last point is obviously pure upside. I have no idea if that will happen or not. I mean, mechanistically, I think historically, we've spoken about the Ebglyss data and the higher order response rates going out to a year, right? When you compare that to Dupixent, it looks like there might be some improvements. Again, we'll have to see with the data. Mechanistically, do you think there's anything when you think about IL-13 relative to IL-4 that could be leading to better durability over time or better maintenance of response over time? Or is this just something you'll have to see with the data? I'll hand it to our Chief Medical Officer to kind of talk through the rationale. Yeah. So I mean, I think that to kind of build on Michael's point, right? On the OOPA and Doopie point, right, they rarely don't see any differences between 16 and 52 weeks. In some ways, mechanistically, they're doing something similar, right? They're both blocking receptors, one extracellularly, one intracellularly, right? That's all they're doing. They're doing nothing to the offending agent. What we have and what Ebglyss does, although they haven't really shown clear cuts of their data here and why we're excited about this, is we are blocking the receptor, too. When 777 is attached to IL-13, it can also attach to IL-13 receptor alpha-1, block IL-4 receptor alpha-binding. We're doing that. We're also able to bind to soluble IL-13, right? That's just kind of floating around in the system. When that complex is unscientifically floating around in the system, it can be penocytosed into cells and degraded as a complex. We are actually reducing the primary offending agent in atopic dermatitis, which we know is IL-13. Not a secondary offender, but that is the primary offending agent, too. That is different than what we have seen there. That could result in a different outcome between 16 and 52 weeks. I am excited to see if that holds and, yeah, that mechanistic rationale plays out in first quarter next year. Wonderful. Thanks so much for that, Carl. All right. Maybe we'll move to part B, that data also now coming a little bit earlier in Q2, which is going to be a very interesting follow-up to the part A results. Maybe you could start by just explaining some of the key differences of the part B study relative to part A in terms of patients, how the dosing compares, and ultimately what you hope to see. Yeah. Carl, do you want to speak to the design of what we hope for? Yeah. Of course, right? Here we're looking at three doses versus placebo, right? Very, I guess, traditional in that sense of a dose optimization study. What we're really looking for is to fully explore the dose response curve here. The low dose is about 50% of the exposures of lebrikizumab or kind of very similar to what their lower 2B doses were. The goal of that dose is really to see where the lower end of the dose response curve is. We know sometimes they call it our regulatory dose, right? They want to make sure you're going forward with the lowest effective dose, right? That'll help us with those discussions overall. The mid-dose, obviously, we've seen really encouraging data that's the same dose as the part A dose, really encouraging data there. Two-thirds of patients respond with an EASI-75. Really excited, would be incredibly excited to replicate that data. The high dose we really put in here because there's just an unknown of where we're going to max out the dose response curve. We want to walk away from the study knowing we're optimizing benefit for patients and didn't want to have that question hanging over our heads after the end of this study. Testing a dose, it's essentially 2x the exposure of lebrikizumab, so 100% greater exposure than lebrikizumab so we can fully explore the dose response curve. I think that success here looks like replicating the part A data, right? Jeff can tell you about the market research we've done and the excitement of KOLs and prescribers behind that. Upside here is the potential to get even better efficacy. We have never wanted to leave that on the table, even though it has not been something that has been demanded by KOLs, prescribers, or really patients. Great. We will definitely get to Jeff here shortly. Obviously, even if you maintain the impressive data that you saw in part A, in part A, you had a historically high placebo response rate, right? When you adjust, you were using a very high placebo rate. Can you talk, and obviously, there are more patients here, so you might see a more normalized placebo rate in part B. Can you talk about the difference in enrollment in patients between U.S., ex-U.S., and what you saw in part A with respect to placebo and how that might impact the placebo rate? Yeah. To your point, when we got out and talked to docs, and I know this was echoed at a well-attended conference in Boston, right? Docs are very excited at our data, and they look to the absolute rate. Right? Absolute, we are 15-20 percentage points better than kind of what is out there, two of three, and one of patients responding to EC75 versus one of two. That being said, we understand that, especially for a mid-cap investor, placebo-adjusted is quite helpful. The key difference here is greater N and closer to a 50% European enrollment versus around 25% in the part A. Right. Just to be clear, you saw lower placebo rates in Europe, right? Yes. We observed what kind of everyone has observed historically, that Europe seems to have lower placebo rates. Nobody knows why, like optimistic Americans. For some reason, Europe continues to kind of trend with lower placebo rates, and we saw the same. We do not want to set the bar that we need to see a lower placebo rate in the part B because, again, all the KOL feedback, patient feedback, the part A data is amazing as delivered, especially now with the rapid itch and the sclerosis-like dosing, we hope to confirm. However, we would welcome it in addition to others. Right. On conjunctivitis, you guys trended similarly to Dupixent over time. KOLs could not be less concerned about it. In terms of these much higher exposures being tested in part B, how do you think that might impact conjunctivitis? Yeah. This is something where there is a good amount of data. When we look at our own data, we saw the lowest rate of conjunctivitis in our highest exposure group, our highest quartile. This matches what Dupixent has seen. As you increase, the first part here is placebo, and then as you go from left to right, it is lowest exposure to highest exposure. You see that as exposure increases for Dupixent, the conjunctivitis rate decreases with that exposure. It is an on-target adverse event that is inflammatory in nature. The more anti-inflammatory antibody a patient has on board, the thinking is the rate goes down, right? All to say, we do not need to see a lower rate to be successful in the part B. When asked, is it driven by, could it be driven by higher exposures? It's actually the inverse based on data. Okay. Great. Maybe to wrap it up before we get to the 279 or Oxford ELIGAN combo data, what is the approximate timeline for the pivotal trial, and when do you believe that you could get to market with APG777? Yeah. We would kick off our phase 3s next year. Atopic derm studies take 18-24 months to read out. That would then set up a 2029 launch. Okay. As a reminder, our balance sheet of $913 million of cash is runway into the second half of 2028, and it provides the runway through top-line phase 3 data. Perfect. As well as the other phase 1 and 2 programs that you have disclosed, right? Yes. As well as the 279, the important readout in the second half of 2026, and some of the early work on the expansions, yes. Great. So again, as we just discussed with part B, there's reason to be excited about that data and especially the arm of higher exposures. You go into the second half where you've got a bold study with APG777 combined with APG990, the Oxford elegant, with the superiority head-to-head versus Dupixent trial. You guys, Oxford elegant drugs, as we have seen, are clearly quite effective. Some people thought that they would compete directly with Dupixent and Ebglyss, although you guys have been remarkably consistent for a long time now that you think it's best used as a combination partner. If you just add the response rates from the two together, obviously, you're seeing numbers that are way higher than Dupixent. What gives you confidence that efficacy between these two will actually be additive? What delta on top of Dupixent do you think you need to show to be successful here for superiority? Yeah. If you were to kind of directly add them, then you get a number that's like a JAK kind of on each endpoint. We're attempting to replicate the JAK-like biology, which JAKs are 20-30 points better on each endpoint. When we talk to payers, physicians, patients, it's pretty resounding feedback that, right, 5 points, maybe it's better, hard to say. 8-10 points kind of becomes a signal that is convincing to folks. Also a signal that can be easily designed to be captured in trials later on. 8-10 points of efficacy on one or more endpoints is our bar for this program to be sufficiently differentiated from Ebglyss. That is coming out in the second half, 16-week data. Similar to part A and part B, you guys are going to look for are you doing maintenance, or what would the pathway forward be for the combination? Kind of a unique design here, actually. Carl, do you want to speak to it? Yeah. What we're looking at here, right, head-to-head, essentially for the first 24 weeks, and then everybody gets their last dose of drug at 24 weeks. From there, we will monitor the maintenance of response over time or lack thereof in all patients for another year after that, too, given the half-life and what we've seen with some of the remitted data, potentially remitted data with Oxford ELIGAN. We think that's an exciting piece of this, too, to see how long that change in effect, right, lasts for after that, too, and be able to compare that to current standard of care. Great. Maybe getting to Jeff, just can you tell us the latest on the market research based upon the initial profile we've observed so far with APG777? Also, how do you think about having both a three and a six-month dose, potentially even an APG990 combo? A number of potential presentations here for patients and physicians. It'd be helpful if you could put it together for us. Yeah, sure, Tyler. I think, first of all, I don't think there's a true appreciation for how preferred this product is versus the competition. Coming out of our phase 2a readout in this summer, we did extensive market research through Trinity Life Sciences with 75 physicians. We used our actual product profile from part A. What we did is put the profiles in front of physicians for 777 and the other available agents. We looked at everything from absolute and placebo-adjusted EASI-75, 90, IGA 0/1. We looked at safety as well as dosing options. We simply had physicians force rank what they would use in their moderate to severe AD patients. 60% of those physicians said that APG777 would be their number one choice. That's 2- 1 over the market leader. You can see Ebglyss had 7%, Nemluvio 1%. Yet I think you're well aware of how strong those launches are right now. Ebglyss is annualizing right now at about $650 million a year, and Nemluvio a little over $500 million a year. It positions us very, very well for coming in and completely disrupting this market. I think to your second question on the Q3 versus Q6 month, we want to make both available. It's clear here that with the Q3 month dose, which is what was added into this profile, we do have the market-leading product. I think that is transformational in and of itself. We want to have optionality for both physicians and patients. We expect to do so. I think from a physician perspective, you're likely to increase market share by about 10% in terms of what they're going to use first-line biologic for their patients by having the availability of the Q6 month dose as well. I think overall positioned very well with our monotherapy. To Michael and Carl's earlier points about 279, there's not a good option for the 50% of patients that do not reach EASI-75 with Dupixent right now. Even when APG777 comes to market and becomes the product of choice, you're still talking about two-thirds of the patients that are reaching EASI-75. We need more options for patients and for physicians. The combination of IL-13 and OX40L allows us to raise the bar from an efficacy standpoint, keeping our quarterly or better dosed option in the market and really allowing patients options prior to going to JAK inhibitors where certainly they have their concerns with the black box warning. That is how we kind of see this developing. Certainly, 777 will be the product of choice early on. We have a sustained runway with this market growing at 25% a year right now. Perfect. We're way over time in the next session, starting in four minutes. I have to ask about 333. You guys just had great phase 1 results, right, with the TSLP. Maybe you could just briefly talk about the plans for that agent and potentially even in combination with 777 and when we could see the next study start. Yeah. Jane will kind of speak to how we think about that with competitor data coming. Sure. Yes, of course. As we look for the combo plans for respiratory, for TSLP and IL-13, we are going to look at the lebrikizumab second-made data that's coming out in the first half of 2026. That will inform their own combination of IL-13 and TSLP. As we see their data currently, that's only about every month dosing. Based on the PK that we saw for 333 that we disclosed earlier this week, we think that supports clearly the opportunity for quarterly or better dosing. We will look for that data. Also, it's important for us, again, to see the part B data for 777 that will also better inform dosing. With those additional data points, we will then plan our phase twos for respiratory indications and will come out with more disclosures on what those trials will look like. Continue to be strong believers in the co-formulation approach over the bispec because, again, the trick here is to optimize the ratio of the two different molecules. We have that benefit with a co-formulation approach. Okay. Wonderful. With that, we'll go ahead and wrap up. Jane, Michael, Carl, and Jeff, thank you very much for your time. It was a great discussion. Thanks to everyone for logging in. The next session is starting in just over a minute. Have a great day, everyone. Okay. Thanks, Tyler. Appreciate it. Bye, everyone.