Welcome us for another fireside discussion here at Guggenheim's Emerging Outlook Biotech Conference. We host this conference every year, and once again, very happy to have the Apogee team here with us today. Joining us to my immediate left is Michael Henderson, the CEO. To his left is Carl Dambkowski, Chief Medical Officer. To Carl's left is Jeff Hartness, Chief Commercial Officer, and Jane Henderson will be up on stage with us momentarily, and she'll be immediately to Jeff's left. So, really excited to have the team here with us again this year. Just as a reminder, Apogee is Guggenheim's Best Idea and has been for, I think, the last 15 months or so. And it's been really an exciting period to follow the evolution of the company as well as the naming of zumilokibart. But let me turn it over to Michael just to introduce the company to investors and to remind folks about the great opportunity that you guys see ahead. Cool. Thank you, Seamus. Thank you, everyone, for coming and for having us. So, you know, very exciting time for us at Apogee. We were founded about four years ago with the idea that patients living with atopic dermatitis and related conditions deserve better treatment options. I think, you know, we're well on the way to that journey, now, you know, with definitive Phase II data kind of behind us last year, showing, you know, really nice rapid itch, you know, nice lesional benefit for patients as well, and we're now on the precipice of proving out, you know, the thesis that the company was founded on, which is: Can we move dosing from an every 2- to 4-week paradigm to an every 3- to 6-month paradigm without any sacrifice, if anything, you know, better efficacy? So we're really excited, you know, to be proving that out, you know, potentially this quarter for patients. You know, getting our fully optimized dose in atopic derm next quarter, kicking off our Phase III studies this year, and then moving forward with a number of combination approaches in both atopic derm and in respiratory conditions across kind of a, a portfolio and a strategy that is designed to be, you know, best-in-class mono and fixed-dose combo therapies for kind of Type 2 inflammation broadly. And yeah, we're really excited to continue the progress, and it's been a very exciting, you know, sort of development, both competitively as well. So we're sitting... You know, you have to be both good and lucky, and we've been lucky to have both so far. Great. You know, earlier this year, we saw the Phase 1b asthma data. Can you remind us, you know, why that opportunity is so important in the context of the opportunity, but also what those data showed and what you believe it represents? Yeah, definitely. Maybe, Carl, you want to speak to the data, then, Jeff, you can talk about kind of pair dynamics? Yeah. So sounds good. Earlier this year, we put out a Phase 1b data in asthma. We looked at 19 mild to moderate asthma patients, and specifically, we were looking at them for two things. One is the magnitude of FeNO reduction. So FeNO is, like, a really good biomarker, has really great correlation with AER, Annualized Exacerbation Rate, which is kind of the approvable endpoint here. And so what we wanted to see was both that we had a magnitude of reduction in FeNO that was similar to other approved agents like Dupi, Tezi, et cetera, as well as a durability of effect that would allow us to do every at least every three-month dosing. We saw a really nice magnitude of change, up to a 60% change from baseline in FeNO, or 45 parts per billion. And then I think maybe most importantly, so that was exciting, that is very competitive with what other agents have seen. But maybe more importantly or equally important, we saw that the durability was really good. For all patients, we had data out to 16 weeks, very flat throughout that whole time period, and for available data beyond that, 'cause it's an ongoing study, we saw it really goes out to 8 months as well, too. So, showing that we can have potentially the magnitude of change that we're seeing with Dupixent and lebrikizumab, but also the durability, and this is really important just 'cause we know a lot of patients have comorbid disease between AD and asthma, and I'll let Jeff talk about that opportunity a little. Yeah, thanks, Carl, and thanks for the question, Seamus. I think adding asthma to our label, it does a few things. First, when you look at the disease itself, you have about a 30% overlap between AD and asthma, and this allows us to unlock the full potential of the AD indication that we will launch with. Secondarily, it pushes us further into the allergist and deeper into the allergist offices, while also driving us into pulmonologist offices. So there's this value around revenue in and of itself. If you look at Dupixent, although it was fourth to market, although it has, you know, every two-week dosing, they are still the market leader in the asthma space, and set to, on track to do over $5 billion by 2028 in asthma alone. I think, I think lastly, what it does for us, is it allows us to, have a, a stronger position as it relates to payers and our negotiations with payers, because really, we, we would only be one of two products in the market that have both AD and asthma for a third of those patients. So sets us up very well for long-term success in both indications. Great. You know, let's jump into the data initially, 'cause I know that's coming up soon. So your Part A, you know, 16-week data, maybe you can just remind us what you saw from your 16-week induction data, and now maybe extend that into how we should be thinking about the Part A maintenance data and why those data are so important? Yeah, no, I'm happy to. So right when we think about what matters to patients, you know, physicians, payers, et cetera, it's really three attributes, right? Patients, especially, they need rapid itch, right? Can you see 48-hour itch relief? Something that, you know, as a patient, that's what their primary complaint. And we've seen Nemluvio launch incredibly well, really just based only on itch relief, right? Without much lesional benefit. Like, we are seeing the same 48-hour itch relief that, you know, Nemluvio sees, with that kind of higher exposure because of that better formulation day, you know, day two. So that was, you know, data that we put out kind of in the fall. You know, also on lesions, which is, you know, what docs really look for, EASI-75 especially, where we're seeing 2 or 3 patients respond compared to one of two for, you know, Dupi and Ebglyss. Again, right, with that higher exposure. The last piece of the puzzle and what we're—the those are both kind of upside pieces. What we were founded on and, like, the piece which test most favorably with everyone is, can we greatly reduce the injection burden? So to go from an every 2- to 4-week paradigm, which leads to, you know, 50% of patients falling off within 2 years to a Skyrizi-like profile, an every 3- or even 6-month drug. That's what we're looking to prove out this quarter, and it's kind of the last piece of the puzzle, you know, that everyone wants to see, because then everything else, it's a bit confirmatory, right? Part B confirms the dose, you know, potential upside, but just upside at a high dose. Right. Phase III confirms the dose, very high correlation. So we're really excited to prove out the potential that we kind of were founded on with that data this quarter. Great. And, you know, there's also that, you know, in terms of how to think about those data, and how they'll be presented, Carl, maybe you can talk about the dynamics of, you know, what are the right comparisons, what are the appropriate ways of looking at the maintenance data itself? And then also just how should we be thinking about the safety and tolerability data as well? Yeah, great. Happy to. Right. So, yeah, one of the unique pieces of our trial design, which has not been true of Lebri and Dupi necessarily, is we re-randomized everybody that was on treatment to every 3- or 6-month dosing. What that really allows us to do is look at patients from week 0 to week 52 over that whole course of the year and see how they do, right? Unfortunately, we don't have a comparator for that. So what we'll do with that patient population is we'll look at, in terms of analysis, we will look at the responders, either EASI-75 responder at week 16 or an IGA 0/1 responder at week 16 and say: How good did those responders maintain their response 36 weeks later or at week 52? That's what we have for Dupi and Lebri. Dupixent has shown 72% of EASI-75 responders maintain their response at week 52, and 53% of the EASI or IGA 0/1 responders maintain at week 52. So those are kind of our benchmarks there. Ebglyss is nominally higher on EASI-75, maybe like 75% or 80%, and a little higher, but a bigger range on IGA 0/1, 65%-75% there. Right? So that's kind of our benchmarks. We think that an additional benefit we had, as I mentioned, is we can see how patients did over the whole course of time, and we'll see what that looks like as well, too. Although the oral marker is Rinvoq, which we know is a very effective drug, badly, you know, weighed down by many, many safety liabilities with it, too. So we maybe don't have, like, a perfect comparator there as well, but, you know, want to see how the whole population is doing over time. In terms of safety, right, really, the only thing we have to talk about with, with zumilokibart and the class in general is conjunctivitis. That's what we'll be expecting to see here, too. What we know is that it's most common in the induction period. You still get cases after the, induction period, so after week 16, but their frequency is a lot lower. There's one Dupi, one Lebri comparator for that, and they've shown over that whole 52-week period that they get somewhere between 14% and 30%, rate of conjunctivitis. So that's kind of the area that we hope to be in there, too. Really to continue to build the story behind, like, the safety of zumilokibart is really similar to Dupi and Lebri, which has been incredibly well tolerated, you know, not only in clinical studies, but in clinical practice. One other factor, I think from your part, a maintenance data, you know, there was some reaction to the conjunctivitis rates, but I kind of feel like there may have been a bit of a misunderstanding, as to the evolution of what physicians started looking for. Yeah ... basically, what we might call ascertainment bias. So maybe you can help us understand, you know, as you've kind of looked at the data and talked to physicians, the impact there as well. Yeah. I mean, I think if you talk to any physician, do doc calls, go meet your best friend for, for drinks that happens to be a dermatologist, they, like, they just don't care about conjunctivitis. It's just, like, not something that is bothersome for patients. It's not something that patients drop off for. So we talk about it 'cause it's a thing to talk about, right? And then I think there's a couple contributing factors at this stage in development, meaning over the course of IL-4 receptor alpha and IL-13 development, that are, are possibly contributing there. One is, you know, people are now asking about everyone's eyes, right? You used to come in, and they'd say: "How are you doing?" Now, patients come in and say, like: "How are your eyes, and did you have any other AEs?" Right. So, you know, as a marker of that, in Part A, in the induction period, about 25% of cases were seven days or less, so like extremely short-lived, with a couple cases that were, like, two or three days, right? Like, I guess that could be caused by drug. It could also be caused by, like, they've visited their friends that have a cat, they have a kid that had pink eye, et cetera, too. So lots of things there. And then the second thing that I think contributes to is just the patient population you enroll, too, right? So we know that Dupi and Lebri studies, even in the induction period, they've had ranges from, like, 2%-25% conjunctivitis, and some of that is just the background rate of predisposing conditions. That can be a history of conjunctivitis, but it can also be things like animal allergies, allergic rhinitis, where you're rubbing your eyes a lot during, like, allergy season, et cetera, too, all contributed to it. And about 50% of patients enrolled in our study had some predisposing condition to conjunctivitis, too, so could lead to a nominally higher rate, but still in this range, right? Importantly, most patients are getting no treatment for it, meaning that the doctor just incidentally notes it. If they're getting treatment, it's either Visine, so just over-the-counter lubricants or antihistamine. So very easy to treat, very well-tolerated. Median duration of a case was just 29 days. I'm adding that because another thesis out there was like, "Oh, they're gonna get conjunctivitis for, like, 5 years," 'cause you have a 77-day half-life. Right. That's not happening at all. Yeah. Dupi, by comparison, was 170 days. Interesting. Like, the bare thesis is just not intact on it. Got it. Okay. Super helpful. You know, let's talk about Part B. So as we kinda lean in on Part B, you know, you have this, you know, materially higher dose going for 100% exposure to Ebglyss. You know, what are you hoping to see in that data set? And can you also talk a little bit about the value of replication of the Part A data set? Yeah. So right, we are the Part B dose, we're testing a lower dose than Part A, replicating Part A as the mid dose, and then also testing a higher dose, which is about 2x lebrikizumab exposure versus the 30%-40% higher exposure that the mid dose is. And, you know, there, we know that there is an exposure response with IL-13. The question is just, you know, are we at the top of that with the mid dose, or is there something incremental to be gained with an even higher dose at the top dose versus the mid? We'll see. I think, you know, when we kind of talk to docs about it, you know, they almost- we say, like: "Well, what if we also had better efficacy beyond, like, what you're seeing here with our profile?" Like, they ki- they... I mean, not to be like, you know, funny, but, like, they kinda laugh, they're like: "Sure." Like, right, like, like you're already gonna win. Like, you already have the itch, you have Phase 1 data at least as good, and you're dosed way better than anyone else. So, like, would we-- nobody wants better, more efficacy than we do because it makes our lives much easier, and it's even better for patients, but it is pure and utter upside versus needing to, help us win because we already have a winning profile, if we can replicate what we saw in the Part A. And there is very high replicability on 16-week data from, between Phase IIs and larger Phase IIs and then Phase IIIs and AD. Great. So I guess the one other characteristic is that, you know, you do have variability in dosing in other areas. So, you know, where you have the opportunity to take Humira and dose it every two weeks, or there's a high intensification frequency that can occur where it goes to one week, is that another sort of opportunity as we think about the sort of scale to allow intensification as part of an ultimate label for physicians over time? Yeah, you know what, I'll say kind of for the... So I'll answer it in two ways. Within atopic derm, you know, when we think about the, you know, even our top dose, we're still not disadvantaged to the every two-week paradigm that others have set. Yeah. So even, like, because of our improved formulation and PK, right, we did both a fully optimized antibody. We're able to, you know, push while still not push exposures, while not actually pushing dose. Yeah. So, like, you don't have to choose between dosing and efficacy, and then there's not that exposure response in maintenance. It is only in induction, so then you can kind of hit it hard, get the active inflammation tamped down, and then, you know, spread out dosing, potentially, to be proven this quarter, with every 3- and 6-month dosing. So it's kinda like it's the best setup for something that can... you know, for a profile of our drug, 'cause you then don't have to trade off between dosing and efficacy longer term. Then, you know, the, the other caveat I would just say is, when we think about the full range of indications that we could go after, you know, like, the one that jumps to mind, it's a very apropos to your comment, is EoE, right? Eosinophilic esophagitis. Only Dupixent's approved, it's dosed weekly. You know, ISR rates in that study were 30, in the high 30%. Very tough disease. So that's, you know, something that's on our radar to go into, and, you know, that, even monthly, would be a huge benefit to patients. I think that's, you know, more work to explore, but that same paradigm could exist. And you guys have talked about the importance of having two factors in any TH2 product, and it is a factor for your own, which is very low ADAs and very low ISRs. So can you just remind us why are those two important factors for any TH2 drug or, frankly, any antibody? Yeah. Jane, please. Sure, on the ISR side, of course, it's one of the main reasons why patients go off of Dupixent, and in two years, over 50% go off of Dupixent because of ISRs. And we always hear from individuals of, "This shot just hurts. The drug works, but it hurts." So ISRs are key. On the ADA side, you know, we've seen around 10% on ADAs, but we've seen no impact ultimately to the efficacy. That's different from what we see and hear on the biosimilars, where ADAs actually can impact efficacy. So on those two issues, for our Part A, we did not see any ISRs. In the future, we would, of course, expect to have some, but nowhere near the rate that we see with Dupi and others. Right. Yeah. And it always just seems like if you could avoid ADAs, why wouldn't you want to do that as well? We've seen, I think, impact to efficacy over time with other potential molecules in the market. That requires them to step up in dosing, and it kind of changes the value proposition. We think it's also one of the advantages of the co-forms, right? Yeah. Because we don't see the ADA issue with a co-formulation approach that you do with bispecific. Perfect setup for my next question. So let's talk about APG279. You know, maybe just as a starting point, the choice of OX40 ligand and some of the, you know, sort of recent updates that we've had with regard to competitor molecules has raised questions around, you know, safety. But maybe you can put that into context, not just from your baseline of what the backbone molecule is and the backbone structure of your, game plan, from a strategic plan perspective is but then, you know, from the realities of the outcomes. Yeah, completely. Right, so our view for both our OX40 ligand and our TSLP, for that matter, is that they are really interesting as a combination partner on the back of, like, our workhorse, zumilokibart, our IL-13. But we are not interested in them as monotherapies, and that's because as monotherapies, right, they're either crowded and/or just not differentiated on efficacy. So our view, right, with 279, which is a fixed-dose co-formulation of IL-13 and OX40 ligand being run head-to-head versus Dupixent right now, the only study being run head-to-head versus Dupi that we're aware of, is right there we're taking. We know that in the future, we envision zumilokibart will be the frontline drug of choice. There will still be some patients that don't respond, right, that need something more. They have more Type 1 or 3 inflammation, and Type 2 alone isn't enough. Well, then they'll need to go to a second-line drug. In the second-line setting, what are the options gonna be? It could be 279, which should show, if our thesis is correct, right, an efficacy advantage of 10 points or so, or more better than Dupi, or they could go to amlitelimab or rocatinlimab or a JAK. Recently, there were obviously cases of 2 cases of Kaposi's sarcoma, one on each Roca and Amli. So, right, 2 out of almost 10,000 patients treated, both cutaneous, both in individuals with known risk factors, like part of certain groups that are known to have a higher background rate of HHV-8, which is the herpes virus, which is the causative form for Kaposi. We know that anybody on an immunomodulatory drug, right, even topical corticosteroids, JAKs, cyclosporine, steroids, if you have HHV-8, then you can get cutaneous Kaposi. Then you come off drug, derms don't look for it, and it can resolve. With Kaposi, I think in the context of Amli and Roca, I think it just adds to, you know, they're not better on efficacy, and now they have, like, this unknown safety piece. So it's hard to see them as, like, being the ultimate second-line choice, right? Because, like, you're stepping down in efficacy. Like, you're not stepping up. There's no good trade-off. Whereas here, we think everyone goes on Zumi, and then it's either, do you want to go to something that could be better, which is our combo, or a JAK? Well, JAKs cause a lot more than Kaposi. They cause Kaposi, they cause DVTs, a number of cancers, and they require labs. So, you know, our view is actually the combo thesis is very much intact because we view it as a second-line therapy on top of our own zumilokibart. And, you know, I think we've talked to a lot of docs, they share that view, and but with the caveat, it has to be better on efficacy. Yeah. Otherwise, right, then there's no value. So, you know, that's our view, and in the meantime, you know, kind of other late-stage approaches, including those, have all kind of had issues and fallen down. So what we hear from, you know, a lot of stakeholders is, "Look, like, IL-13, we know it's safe, we know it's effective. Prove this out. Like, there's nothing else out there that has the potential to transform frontline usage. Maybe that'll kind of take us a step back to, where do you feel Zumi is, in the sort of next-to-market opportunity? Who could come to market next, and what risks would be necessary for them to close even a part of that gap? Yeah. Please. Yeah, I think. Well, we are the next first-line agent. I think if you look at, you know, who's potentially launching ahead, you know, amlitelimab, obviously, I think, clearly, and regardless of safety-side effect profile, I think if you talk to physicians, Roca, Amli, they were gonna be second-line agents anyways, right, based on efficacy alone. You know, the one thing that patients want is they want this to work quickly, right? Itch, lesion control, and certainly we've seen those numbers, EASI-75, EASI-90, much lower than the first-line agents with Amli and Roca. We are bringing forward- ... as good or better lesion control than Ebglyss and Dupixent. We're bringing forward a statistically significant 48-hour itch like Nemluvio, and we're bringing forward the dosing that physicians and patients really want, quarterly or better. So, we are the next first-line agent. I don't see another mono, combo, bispec, anything launching ahead of us, puts us in a really good position to come to the market and actually challenge Dupixent for the number one product, biologic product in the AD space. We plan that launch in 2029, so this decade. Mm-hmm. Great. And Jane, maybe just to follow up on that launch specifically, remind us what is kinda necessary and sufficient. You know, what have you sort of built and thought about from preclinical stage all the way through, you know, kind of the launch timeframe, you know, whether it be from, "This is the necessary cash to kinda get us to this point," but also, "These are the pieces of the puzzle that make for a great franchise," end to end? So starting with the easy one, the cash, we have over $900 million of cash. That's cash runway into the second half of 2028. That provides runway through our Phase III top-line data, and that's 2 replicate trials versus placebo. And then what we've built from the beginning, from the preclinical private stage, and we're almost now a 4-year company, is envisioning what it would take to launch this drug. So making sure we optimized the formulation, as we talked about. We optimized the manufacturing process so that it's a high-yield, high-titer process, which means when we're launching, we can see where we'll have low single-digit COGS. We've also made sure, from an organizational point of view and operational, knowing what the target product profile should look like, not just from physicians and from patients, but also as well as the FDA, but what do the payers care about? That TPP is equally important to them, and having the insight of Jeff and his team to make sure that that's built into the design, along the way. As we look at launching the drug, we can do that with a sales force that's similar to Galderma or Ebglyss, and that's about 150 reps. It's that early foresight and that early planning that means that we can say with confidence that this launch will be in 2029. Super. Well, unfortunately, we didn't have enough time to cover your TSLP and broader pulmonology opportunities, as well as EoE, but obviously, lots going on. Looking forward to your Part A maintenance data and, you know, many successes through the balance of 2026, and obviously into the start of your phase-