Good morning, everyone. Thank you so much for joining us. Really pleased to have the Apogee team with us and from the company, Michael Henderson, CEO. Michael, to start here, can you give us a snapshot of Apogee today and what your priorities are for the second half of the year? Yeah, so Apogee, we're developing best-in-class monotherapies and combinations over time going after the largest markets in I&I. So atopic derm, COPD, asthma are the ones that we've disclosed to date. And with our lead program earlier this year, we showed kind of proof of principle with our initial drug that we can take known, validated targets and make much better antibodies. So the upshot is for our lead, we hope to have a SKYRIZI-like every 3- to 6-month profile in the largest market, atopic derm. Second half of this year, we're going to hopefully rinse and repeat that success with our IL-4 receptor alpha DUPIXENT-like antibody with the initial kind of proof of concept PK data. Second half, we'll also then start to share more around our combination approaches, which is where we're going to share more and more over time because we think that we can be first movers with some combinations as well. Can you walk us through this longer-term strategy here that you have with regard to the assets and the combination approaches and how this fits into your clinical development strategy? Yeah, so when you look at kind of companies that have built incredible commercial kind of made the leap, reached escape velocity, if you will, from biotech to fully integrated land, it takes that kind of that $10 billion-plus drug to reach that really escape velocity, that Vertex-like, that Regeneron-like place. So with our lead, we think that we have that for atopic derm. If we can execute and deliver on what the data tells us, we should be able to reach in terms of efficacy at higher exposures and dosing, then we could have a best-in-class monotherapy for atopic derm, follow that with pipeline end product expansion, potential for asthma, COPD, et cetera. But then over time, we don't want to kind of we don't want to wait and let others then come behind with better combinations. We want to be the first movers and have first-in-class, best-in-class potential with combination approaches, which will be just co-formulations of our best monotherapies. That helps us to move quickly, maintain that 3- to 6-month dosing paradigm in a single 2 mL autoinjector, and really kind of never stop at good enough for the patients that we're seeking to serve. Regarding IP, can you help us understand what Apogee has protected and why investors should feel comfortable on this front here, just given the approach? Yeah, of course. We get a lot of questions about IP. It's interesting. One analyst told me, yeah, there's somehow 20 FcRn companies, but nobody believes that you could have FTO in this space, even though you're just the second IL-13, really, after this epitope. So the company was founded on the basis of a strong FTO search and patentability search. People cannot or at least people have tried, but the Supreme Court has said you cannot patent an epitope. You cannot patent a gene. So what we do with each of our programs is we started with a YTE onto a lebrikizumab, a YTE onto a DUPIXENT, YTE onto amplifier. We then spent significant time, years, $10s of millions, non-human primate head-to-head studies to generate a much better antibody than that initial obvious thought of just adding YTE into something. The proof point is with our lead, we're not just getting a 3x the half-life. We're also at a 50% higher formulation. We're seeing decreased variability. We're seeing great bioavailability. We're seeing improved solubility and viscosity. So we aim to make the best version of a half-life extended antibody. We don't know what the answer will be at the beginning, so we test everything. We then get to a non-obvious answer, which when you talk to a patent examiner, non-obvious is what they're looking for. So our initial IP has started to be published. Our 777, a piece of IP got published towards the end of last year. People have now started to be able to take a look at what we've done. Everyone should consult their own IP attorney. Appreciate the work that you did speaking to a KOL in your initiation. I think that when you do that, you see that people come back and say, yeah, this looks to be quite defensible. Not only is there FTO, but there's strong patentability for composition. We're going to continue to kind of file and choose what not to file, just like any company would do in this space. As you mentioned, you're evaluating 777 in asthma in addition to 808, which you're also evaluating in COPD. How are you going to ultimately decide which one to bring forward, and how are you using your asthma learnings to inform COPD and vice versa? Yeah, so that's something that we're actively thinking about because there's just been at ATS just last month, there was post-hoc analysis of lebrikizumab and their prior asthma studies showing that in the high eosinophil exacerbation group, the Dupixent-like group, that it did show pretty profound efficacy. We're excited to see what our 808 data looks like later this year, see if we can kind of get to a 6- to 8-week bar, which is what we think needs to happen for differentiation that matters to pulmonologists and allergists. And then take a look at the data and figure out what is our best path. We're in a really nice position to be able to think through portfolio strategy with a potentially best-in-class IL-13 and a potentially best-in-class IL-4 receptor alpha, both of which could work in asthma and COPD. The nice thing about asthma is that you don't have to run it. Used to be you needed a phase IIb AER study to see what the exacerbation looked like to get an answer. Now, FeNO has been a great biomarker that the FDA has started to say is a really exciting surrogate. Well, they don't say exciting. They say a potentially informative surrogate endpoint. And that just after four weeks, you can see improvements in FeNO, which have shown pretty nice correlation with FEV1 and exacerbation. So initial FeNO data for both compounds, I think, will be quite telling about their relative profile in both asthma and COPD. You've spoken about the interest in or intent to launch ahead of biosimilar insurance for DUPIXENT. Can you speak to what is driving your confidence here as you think about how commercial dynamics might change post that situation? Yeah, so we don't know when, or at least I don't know, when Dupixent biosimilars will launch. I think that Paul's been on recent calls saying that they have the former Humira team and that there's IP that goes from 2034 to 2040. They're innovation patents is the term they use. Publicly, there's 80 different pieces of IP out there across 20-plus families. Looks very similar to the Humira approach. Composition is 2031, 2032. Even if someone enters day one, we plan to launch at the end of this decade ahead of biosimilars, which I think is just critical to help us have the best launch possible and get patients onto our drug. I think whether or not they get to 2040 or 2034 wouldn't hazard a guess. But typically, litigation takes four years. So I think they will have a lot of incentives to push it out as far as they can. And this is just what we've seen filed today. Worst case, 2031, someone enters, none of their IP does anything to extend. We still will be able to launch before biosimilars. And when you talk to patients and physicians, our profile, it's just overwhelmingly positive. I'm not saying that to be like I am biased, but they love the idea of a 3-6-month dose drug. It's how they've seen these markets develop. It's how they know when. So for us, it's about making sure that we're available and they have access. In that context, long term, how do you anticipate the I&I markets will be divided between branded biologics and biosimilars and combination approaches and new mechanisms of actions? It almost seems like you look at Humira and, let's say, Enbrel. You have patients who just subsets who do better on either drug. So how are you thinking about that in this space? Yeah, so these are heterogeneous diseases. We know that. I think DUPIXENT, it's a great drug. Still, half of patients are getting the 75% clearance, which means half aren't. After 2 years, half of patients that did respond have fallen off drug use because of whatever reason, often needle fatigue. I think that when you look at psoriasis, IBD, really any I&I market, these aren't winner-take-all markets. Psoriasis has 7 different drugs, biologics, doing more than $2 billion this year. Patients, there's really only one compound to date. I think that longer term, you don't need 20% $5 billion drug. With the phase 1 in healthy volunteers, that data and how you think it should translate to that next upcoming readout? Yeah, so what we showed was it's really exciting. So typically, you just don't know as much as you know about a drug at this stage. However, we have lebrikizumab, and we have an overlapping epitope. So we can really show their epitope, their potency, that we match it across all functional assays that we've tested. What we also have from them is a 2,500-patient pop PK model. So Genentech, back when they had it, they do pop PK model like this as well, kind of put out all the parameters so that you know what exposures look like over time. From that, we're able to show not just how our dosing will be different, but how our exposures compare to lebrikizumab via this pop PK model based off of the data that we generated in our phase one and forming our own PK characteristics. And that shows that over time and during the first 16 weeks of induction, we're cutting doses in half versus Lebri, and we're still reaching 40% higher exposures than they did. And we can kind of circle back as to why that's important. Then in the maintenance phase, that we're matching them at 3- and 6-month dosing intervals. So it's almost as if you have what should be the answers to the test, and then you're designing the proper experiment to test your hypothesis, which is just it's truly unique. Typically, you're doing dose binding. Here, we're doing almost dose-confirming studies. And then what's also exciting is Lebri, they did a phase IIB in the past when it was Dermira prior to Lilly, and they only ever tested up to a certain dose. And they never went higher than that because DUPIXENT existed, and they never wanted to be disadvantaged to DUPIXENT. They went up to 2 mL dosed every 2 weeks, never higher. IL-13, incredibly safe. No issues there. We reached 50 exposures in chronic tox with no issues. So we're excited to actually be the first to test IL-13 inhibition at the exposures that we're testing. And lebrikizumab's EMA approval, which is kind of the last piece of the puzzle in Q4 last year, showed that at 30% higher exposures, which there were 180 patients that were low weight that got that exposure, they actually saw a really nice exposure response model. And not one or two points, but running that experiment to see if not, can we also bring greater efficacy via the monotherapy. The phase II trial design, could you provide an overview on that program and what you would expect in terms of data in the second half of next year? Yep. So we're running an integrated 2A, 2B. So second half of next year will be this 6-week induction data off of the first dose. So it'll be 30%-40% higher versus placebo. As soon as the phase IIa sites are done enrolling, the phase IIb will commence. So then depending on enrollment, roughly 36 weeks after the IIa induction, we'll get the 52-week maintenance, and then we'll get the IIb data as well. And we wanted to integrate the trial because we didn't want to for us, it wasn't a question of do we think it'll work. We believe that it should based off of everything that we know. How do we generate some initial data, enable maintenance data that will come prior to phase III start, but still march as quickly as we can towards that IIB readout, which will optimize our dose and enable phase IIIs? Perfect. And I think we touched on this, but you've mentioned that phase II exposure is designed to exceed lebrikizumab in induction by 30%-40%. Do you expect this higher exposure to lead improvement in efficacy in addition to reduced injection burden? So how should we think about that aspect? Yeah, so a question that we often get is, do you need, should we expect better efficacy, and do you need that to win? The answer is no and no. I do not think that we need that to win. SKYRIZI, again, not to harp on it, but it does show that even versus Tremfya and every eight-week drug with the same efficacy clearly wins. So I think that alone helps us win. What we have is we have a really nice exposure response trial effectively that the EMA shared the data on from lebrikizumab's phase IIIs, and we're just going to be the first to test it. Could it lead to better efficacy? Yes. Do we know that it will? No, it's just a data-free zone. So we're running the proper experiment to see, but we don't need it to win. Lebrikizumab's development in asthma was discontinued due to mixed phase 3 trial data, though post-hoc analysis suggests it's efficacious in patients with Type 2 disease. Can you discuss the learnings and how this informs your approach and target? Yeah, so it's almost it reminds me a lot of all the COPD studies that had to be run for DUPIXENT to eventually figure out how to run the proper study and figure out what is the eosinophil cutoff? What is the exacerbation cutoff? So back when Genentech ran their phase IIIs in asthma, one, they used a very low dose, about a 4x lower dose than what eventually would be proven to be the optimized for them dose in atopic dermatitis, the go-forward dose. They just went for it. They did all comers. You don't even need any history of exacerbation. And I think that's where a lot of the field was at that time. It's where COPD was at that time, too. People just kind of enrolling regardless of eosinophil cutoff, regardless of exacerbation. What we've seen now, and in such articles titled like The Rebirth of Lebrikizumab in Respiratory Disease, is when you look back, they were large studies. You can actually see post-hoc being one of those post-hoc analyses that if you had high eosinophils and/or if you had at least one exacerbation, then you hit regardless. If you had both of those, which is what later the Dupixent studies would actually try out, high EO and at least one history of exacerbation, then it looked very compelling. So I think that we have a lot of data to believe and justify that it should very well work. Mechanistically, there's no reason at all that it should not either. So we have a lot of conviction in the study. We're excited to launch it next year. When we kind of were thinking about there's 20-plus different expansions that we could have gone into because of that pipeline and product potential, and DUPIXENT validated so many of those, asthma was kind of front and center because of, one, just the tarnish from those past studies and people saying, "Oh, well, I get filled, so it doesn't work in asthma." But two, the 30% overlap that exists between moderate-to-severe atopic dermatitis and asthma. So we're already prescribing our drug to second-guess themselves and think, "Well, we want to run the definitive study and prove it. What do you think the optimal combinations are here on the forward with your portfolio? Yeah, so we've disclosed one to date. We'll share more later this year. And we added a target, which gives us more optionality, and we'll also share that later this year. But two years ago, we thought, "Okay, what's the optimal combination for atopic derm? And do we want to do bispecific, or do we want to do co-formulation?" We landed on co-formulation for a few reasons that we'll walk through, but also OX40 ligand. The reason being, atopic derm, there's just two mechanisms that have ever worked: IL-13/IL-4 and then OX40 ligand. TSLP failed. IL-22 cytokine failed. Leo's ligand receptor might work, but it's early days. Everything else just did not work. However, OX40 ligand, it's kind of this broad upstream mechanism, which it doesn't rapidly stop inflammation. It kind of dampens things overall. And I think you can see that in the data. So IL-13, IL-4, it really slams type II inflammation down. 95%+ inhibition of the type II pathway, which drives a lot of atopic derm. However, it doesn't touch type I and doesn't touch type III. OX40L hits them all and suppresses them 50%-60%. You see that in the cytokine data that they've just released. So it's the perfect orthogonal mechanism that helps you to drive type II a bit further, but then also hit type I and type III. And when we were thinking about, is there any proof point in this, it's JAKs. JAKs hit all of those. They just have a safety issue. So we want to get to JAK-like efficacy with a cleaner safety profile via those two targets. And we think that there's the most data to date by far because those are the only two validated targets in atopic derm. Yeah. How do you think about OX40 versus OX40 ligand? Sorry, my daughter had her birthday party two weeks ago, and my wife and I are still recovering. I hear you. I had mine last week. Oh, yeah, yeah. I feel bad for everyone who was next to me on the red eye last night. So OX40 ligand, OX40, it's a very interesting debate that we're glad that we chose OX40 ligand as kind of the short answer. Sanofi, they're betting a lot on OX40 ligand. Six different phase IIs. It's like when they're asked, "What are they most excited about in the pipeline?" It's OX40 ligand. So they're developing it across a much greater number of diseases than Amgen is for OX40 so far. We love that because we can be responsive to the data. We chose OX40 ligand a few years ago because of initial safety signals that OX40 was seeing. I think Amgen, it's no secret, double-digit rates of pyrexia and chills. Dermatologists, if you have one that doesn't give you anything, looks very clean like OX40 ligand or the pyrexia and chills, you don't want the call. I want to buy a chance that you're going to get a call regardless of when it comes. You don't go into JAK because you want to deal with safety issues if you can avoid it. So OX40 ligand looks to be much safer. I think the counterpoint to that is, well, maybe you get more efficacy with OX40, but the data doesn't support it. phase IIB trials, maybe the phase IIIs change, but the IIBs, one looks better by two points on EASI-75, and the other one looks better by two points on IGA 0/1. They look to be the same, and OX40 ligand looks to be quite safe. There are other companies now coming with dialing out the ADCC properties of OX40 and saying that it doesn't impact any efficacy. That could be true. Amgen says the pyrexia is the sign of the T-cells burning off. It's needed for efficacy. We don't have to worry about it with ligand because it looks so safe, and we don't feel that we're sacrificing anything with efficacy. With 808, we're expecting healthy volunteer data from the phase I in the second half of the year. What would be a successful outcome from this data, and what can we expect from the release? Yeah, so look for the release to look similar to what we did for the phase I for 777. I think we look to tell a very complete story. We do have a population PK model for DUPIXENT as well, so we'll be able to compare our exposures to theirs. I think one thing which is important to remember is IL-4 receptor alpha. It has that receptor component of it. So it does have a we will have a shorter half-life than we had with 777. It's just biology. If you have that receptor half-life, there's just more turnover. There's more target-mediated drug disposition, TMDD, that will lead to a shorter half-life. That's why DUPIXENT is an every two-week drug, and lebrikizumab is going to be an every four-week drug. So when we talk to physicians, what is the bar, especially in COPD, where we're initially focused? They don't say an every 3-month drug. They say, "Look, people are getting excited about TSLP dosed every 4 weeks, even though it's with 2 injections." 6-8 weeks, I think, would be quite meaningful and would be for these very heavily treated COPD patients that don't always have the best compliance, where you don't want to see C-trough levels dipping and potential exacerbations happening. An every 6-8-week drug is the bar. Got it. We're also expecting proof of concept in asthma in the first half of next year, which is set to include predictive markers of phenotype. What will we learn from this data? Once the data is in hand, what are the next steps to bring that forward? Yeah, so we thought that for the phase 1b sort of MAD data, that it'd be very informative to help us to enroll some asthmatic patients in that. We saw part of this was we saw Sanofi do it with their nanobody and show that in a small number of patients, you could really get exciting FeNO data, which helps you to, one, know that you have an active drug, but two, to validate the dose of it. Making sure that the COPD trial, which we're going to enroll starting next year—which it's harder to find some COPD patients, especially those exquisite type II versus mild to moderate asthma—that we will be taking a dose into that trial, which we know works and that we know what pheno improvements you get in a small number of patients to then maximize the odds that we'll see what we want to in COPD. Great. On 990 and the pipeline, what's the rationale of going after simultaneous inhibition of IL-13 and OX40 ligand with APG279? Yeah, so this will be our co-formulation of the two. And I think atopic derm, it's primarily type II driven, primarily. However, there's a lot of other pathways occurring. And this is why we see, unlike in psoriasis, where we're getting this PASI-90, PASI-100, derm's just not there. Atopic derm, we're talking 30%-40% getting the EASI-75, 20% getting the EASI-90. And it's because, while yes, it is predominantly type II, so many other pathways like TH17, 22, interferon exist and help to drive these pathways, which keep lesions around and keep responses incomplete. When we look at more severe patients, patients with more of an Asian ethnicity, or patients that are younger, we see more TH17 and 22, for instance. So OX40 ligand, it hits all those pathways, just not as fast. And that's why at 16 weeks, it's only getting half the efficacy of the IL-13. So we want to hit the type II pathway hard. We're going to be testing currently in our trial for 777. Just if we hit it with that greater exposure, does that translate to greater efficacy and faster efficacy? And then we just know, though, that there will be some patients that still don't get response because of type I or type III inflammation. So OX40 ligand will help to hit those pathways as well. And because both are so safe, we should be able to co-formulate it into a single 2 mL autoinjector delivered still once a quarter and get to that broader, deeper efficacy across the full population. Is there a subgroup of patients where these assays could show better results in the context of what you just said? Yeah, I think a more Type 1 or Type 3 driven. So I think if you look historically at the different trials, Asian patients do worse. Japan, Japanese patients in particular, because there are quite a number of sites, you see that they do worse. You see that more severe patients don't do as well. And you see that children, which are 40% of moderate to severe atopic derm, an astounding amount. And penetration, there is so much lower because parents just, "I don't want to give my daughter an injection every two weeks," even though she has atopic derm. It's just not worth the psychological pain. They don't do as well. And it's because they have these other inflammatory pathways. Okay. Let me open it up to the audience for any questions. Maybe just here on the forward strategy, what do you think is not well understood about the company that needs to be that partly data will lay out, but also strategy? Yeah. I think, and this I feel like a lot of companies say this, but just the size of the opportunity here. I think the people, they often compare us to other phase II companies in I&I. But the atopic derm market and the markets that we're going after, they're just the biggest out there next to obesity. And the lack of relative competition for such a large market just still surprises me. There are people out there, but we don't have to get a 35% market share drug, which is what SKYRIZI had just a few years in, to have a blockbuster. Each point that DUPIXENT gets is a $1 billion top line. And atopic derm, we all know it now, but it's just six years in. It's still maturing. There's so much unmet need left that I think people don't understand always just how differentiated we could be and how large our opportunities set could be. Great. Question over there. Michael, you spoke about the integration of the phase IIa and phase IIb for 777. For 777. But as we think about other ways that you could potentially accelerate the development path to ensure that launch before 2031 timeframe, are there any kind of levers that you could look into further? Yeah. So we're always looking to see what we can do faster and what we can do at risk as well to help kind of speed along that pathway. So for instance, most companies, they don't do a maintenance arm until the phase III. I think that we're the first phase II atopic dermatitis trial that includes maintenance that will include OLE because we want to generate that data very early to then go into our phase IIIs not wondering, "Huh, should we take the safe maintenance arms or should we take the data-driven approach to get the arms that work?" When we think about our strategy, we've kept capitalizing the company now into 2028 with over $800 million in cash, not because we just want to have a lot of cash on the balance sheet, but so that we can be thinking about how do we start to take the risk and prepare for phase IIIs to launch as soon as we have the data. How do we make the CMC investment so that we're not launching with a prefilled syringe, but with an autoinjector? How are we thinking about commercial scale-up so that we're not running bioequivalent studies later? How are we thinking about adolescents on the label as early as possible? And how are we thinking about expansion indications so that we're not launching for just 60% or 70% of the atopic derm population, but giving physicians at launch the conviction that any comorbid patients, they can also treat with our drug? It sounds like from this discussion that we're going to hear about new targets going forward. Mm-hmm. Okay. When would we? Yeah. So as part of the recent March raise, we did add a new target to the pipeline. We'll share that target in the second half of this year. And it's a target that really kind of helps us to double down on the combination approach. We want to kind of be thinking about how do we get our monos to market to be as differentiated as possible. But then how do we further build out our competitive moat and bring those first-in-class combination approaches? And that'll be second half of the year, and we'll have an R&D day as well that starts to put out some of the preclinical and other data that has gotten us so excited about it. Perfect. Well, with that, Michael, thank you so much. Thank you. Really appreciate the discussion. Great questions. Thank you.