Great, thanks for joining us again, everyone. It's my pleasure to introduce the Apogee Therapeutics team. We have CEO Michael Henderson, CMO Carl Dambkowski, and newly appointed COO Jeff Hartness joining us today. So quite the lineup. And maybe I'll kick it over to Michael to give a brief company overview, and then we'll jump right into the Q&A. Thanks. I appreciate it, Alex, and I'll just update you a quick moment. Jeff joined as CCO, so Chief Commercial Officer last week. Very excited to have him on board. So Apogee, we are developing potentially best-in-class antibodies. We're after the largest markets in inflammation immunology, specifically best-in-class monotherapies for atopic derm. We're currently in phase II, with that critical data coming next year, what we think could be a best-in-class treatment for frontline patients overall. Then, and that's our IL-13 inhibitor, a broad pipeline behind that, including IL-4 receptor alpha, OX40 ligand, and TSLP as well, which help us to come with first-in-class combination approaches across the rest of Type 2 inflammation. So really excited about the pipeline that we have. I think we have the potential to become a leading, if not the leader, in biotech in these conditions, and excited to kind of dive into it today. Yeah, so let's kick things off with 777. And I wanted to ask this question up front, just sort of setting the stage for what is 777, and, you know, why is it not just lebrikizumab plus a YTE slapped onto it? How did you design the molecule, how is it unique, and how does that contribute to, you know, unique IP? Yeah, you know, great question, and one that we've gotten kind of over the years. I think that, you know, it's important to remember we've been at this for a number of years now. We're the company was in stealth for quite some time. We've raised close to $1 billion to not just create a good antibody, but the fully optimized antibody that we can against IL-13. So many years ago, when our IP started to publish, people are now seeing this. We started by adding YTE on the Lebrikizumab. When you do that, you get an okay antibody. It's just not you still have all the baggage of a 20-year-old IgG4, you know, hard to formulate, high viscosity antibody. What we then did is we tried out different backbones. We tried out different half-life extension mutations. We tried out different formulations. The end result is something that is a very stable, much higher formulation concentration, right, 180 mg per mL versus 125 mg per mL, antibody that also has 3x the half-life of Lebrik. So, you know, 50% greater concentration, 3x the half-life. That's how we're going from Lebrik's every 2-4 week dosing out to every 3-6 month dosing. That also enables us to explore higher exposures while still decreasing injection burden, and I'm sure we'll get into that, but we believe that could lead to improved efficacy as well. Yeah. No, definitely, helpful overview, and I did want to start then with the, well, highlights from your phase I data back in March. Seems like a long time ago now, but just back in March, maybe sort of the key highlights as it relates to, you know, achieving that product profile that you hope to. Yeah, happy to. Mid-year readout that we were really happy to bring in March of last year or this year. Carl, do you want to kind of speak to the highlights of that data readout? Yeah. No, happy to, and a lot's happened since March for us, too, and I know we'll get into the other programs, but I've also entered two other programs into the clinic since that time and launched our phase II trial. But on APG-777, and probably many on this call familiar with the data, but just as a reminder, we released interim phase I data from our healthy volunteer study. You know, really looking at safety, PK and pharmacodynamics. You know, highlights really are well-tolerated safety profile in line with the class, right? What we would expect for an IL-13-targeted therapy, which has really shown to be incredibly safe, and we're showing that in our phase I trial. Second, is the optimized PK profile. You know, really building on the engineering that the team did and Michael discussed, but a 75-day half-life for APG-777, that's 3x the half-life of lebrikizumab, and 3x the half-life of kind of your typical monoclonal antibody. It also showed dose proportionality, so looked really good on those parameters, and low variability overall, too. That's really nice because that helps us, you know, be able to better predict exposures patient to patient, so could help with the ability to predict responses patient to patient as well. You know, and then I think a really exciting piece from the healthy volunteer data, too, and not something that you're always able to show from healthy volunteer data, too, was really important and meaningful impacts on pharmacodynamic markers and specifically kind of the two key biomarkers for IL-13-targeted therapies, as well as atopic dermatitis. The first one being p-STAT6. That's kind of the first downstream marker after the key event for atopic dermatitis, which is the heterodimerization of IL-13 receptor alpha one and IL-4 receptor alpha, with IL-13 as the glue in between. So when that comes together, that complex come together, that's the key signaling event that leads to the cascade of inflammation that is causative for atopic dermatitis. The first thing that happens after that complex comes together is phosphorylation of STAT6. What we've shown is near complete and prolonged inhibition of p-STAT6 for up to and including three months after a single dose of APG-777. At the time of that data cut, that was just the longest follow-up we have, so we're continuing to follow that up and excited second half of this year to show additional follow-up data on that. Really exciting, right? The near complete and prolonged inhibition. The second piece that we showed in terms of pharmacodynamic markers, which I think is really exciting, too, is TARC. You know, if there's a biomarker for AD, it is TARC. It's correlated with severity. It shows changes after effective treatment, et cetera. From what we showed there, in a non-head-to-head comparison, is similar maximal inhibition compared to Dupixent, who also looked at TARC in a phase I healthy volunteer study. But again, prolonged inhibition compared to Dupixent. So, they kind of show rebound after, you know, around four weeks in TARC in healthy volunteers, and we showed sustained inhibition up to and including twelve weeks. Again, just the longest available follow-up we had at that time. So, you know, really exciting for us is we're taking validated biology into the clinic, but optimizing the profile of APG-777. I really think this data really showed both of those points. One, the validation of the biology both through p-STAT6 and TARC, as well as, you know, the really optimized profile and the potential to enable every three- to six-month dosing with that 75-day half-life. Yeah, and to that point, you're now in phase II. Carl, you've talked about sort of the rationale behind the design of your phase II, combining a protocol for the II-A and the II-B. Maybe can you talk about the design of the trial, the reason to include both those under the same overall protocol, and then any similarities or differences versus other contemporary studies, at least for the induction trial? Yeah, so great question, and yeah, the phase II trial currently ongoing. We announced our first patient in for that in May of this year, so now ongoing for four months, also seems like a short and long time ago, all at the same time, but a couple key aspects to the trial is one, as you said, Alex. We're combining kind of proof-of-concept portions of the study with dose optimization portions of the study, so your traditional phase II-A and your II-B component, and we're putting that into one protocol, and what that really does for us is it accelerates timelines towards BLA. If you think of kind of the, quote, unquote, "typical path," you know, you finish your phase I-B, your phase II-A study, you look at the data, you think about the next protocol, you restart up sites, et cetera. That lag between the two studies can be months, but as often, you know, a year or more in between them. So by including these in all the same sites in both parts of this, we really maximize operational efficiency and can save months or years in our path towards approval. A second key piece of it is the phase II-A or the Part A portion of it, which are proof-of-concept portion of it, which we'll read out second half of next year. And this is about 110 patients randomized two to one to APG-777 or placebo. Now, that n is really important to us because you know a lot of data we've seen from you know early stage biotechs in AD or any other indication are very small sets. But that 110 patients actually gives us greater than 90% power for the primary endpoint. So this is a real and meaningful readout, and we're reading out the key atopic dermatitis endpoints at 16 weeks, which is what Dupixent has shown, what lebrikizumab has shown, right? And so we'll really be able to take that second half of 2025 data and compare it to what others have done, both in terms of, you know, size of kind of phase II-B type studies, usually, as well as, timing of the endpoint overall. And we've seen that historically, phase II data for atopic dermatitis has correlated remarkably well with phase III data. Like, the correlation is much, much, much greater than point nine in terms of R- squared, which, having worked in other disease areas before, is not that common overall, too. So a lot of things going into the thought behind that design and getting real and meaningful data second half of next year, but also optimizing our path towards BLA long term. Yeah. Yeah- The other piece I would just plug on this study is, we have maintenance coming right after that. So the first phase II in atopic dermatitis that does include maintenance as part of the trial design, which is not only very friendly for patients and, right, and in a world where you are competing for enrollment, right, a very, I think, compelling value proposition to be able to put forward to sites and patients. But also, we'll then have an initial maintenance data on both the three- and six-month prior to starting our phase IIIs. So it won't be a question of will we have an every three and six month, it'll be, what are the doses that optimize having both for launch? Sorry, Alex, go ahead. I was just gonna say, Michael, you mentioned obviously part of the design elements of seven seven seven is the, you know, concentratability and the formulation, and you're also gonna be testing this higher concentration and higher exposure in your phase II. Yeah, I guess, like, how strong is the evidence, in your opinion, that there is a clear exposure response to lebrikizumab and that you could potentially drive, you know, superior outcomes in your phase II at induction? Yeah, I think, there are two pieces of evidence. I'll let Carl kind of speak to it, in greater depth, but there was a phase II-B showed remarkable, I think, dose dependency, so a very nice, dose-efficacy relationship. That top dose tested, which was what could be fit into a two-millimeter injection dosed every two weeks, so effectively what can match Dupixent's dosing regimen, the highest dose that was ever tested for Lebri. That was the, then the only dose taken forward to the phase III. And the EMA data, that came out end of last year, or just ahead of Christmas, showed that there was, within, those thousand patients tested, a very nice exposure response when you looked at the different weight groups. Carl, you want to speak to kind of what we saw there? ... Yeah, so, as Michael said, the EPAR, the EMA review documents, from the lebrikizumab approval now, we're waiting on the FDA ones, too. Lebrikizumab was just approved last week, in the U.S. And, you know, they showed, two pieces kind of within that I think are really important. One is this, weight efficacy relationship, and why that's important for exposure is as you increase weight, this is true of just about any monoclonal antibody, you decrease exposure. And what they showed is as weight went down, efficacy went up, and it's not kind of a little hint here or there, it's a very strong relationship across weight groups, across every key endpoint, including the most stringent endpoints of EASI-90 and IGA 0/1. So really strong evidence there, I think, pointing to the fact that there, there's something there. They also had within there, they talk about the exposure response model, and, you know, it's pretty brief, but say essentially exposure's predicted response. Yeah. So I think kind of, you know, Michael said, too. I'll split that into kind of three data points, the phase II-B, the weight efficacy relationship, as well as the exposure response model. So three points of evidence saying we need to test the hypothesis of whether greater exposures are gonna lead to greater efficacy. Now, I say that, but I also wanna, like, caveat that in every discussion we have with KOLs, one-on-one, blinded, whatever it is- ... or market research, they all say every 12 weeks is there, every three months to six months is transformative- ... even with equal efficacy to, you know, Lebrik and Dupi, which are every two weeks for Dupi and two to four weeks for Lebrikizumab, too, so still transformative even with equal efficacy data, so this is really kind of icing on the cake for us. And we've designed our Part A regimen. I talked about the Part A, that 110 patients, so we'll read out induction, the 16-week induction data next year. We've designed that to tap into it, so it has 30%-40% greater exposures. ... compared to lebrikizumab, which is kind of similar exposures. We designed that because that low-weight group, that 60-kilo group, that did the best, in terms of efficacy endpoints, had 30%-40% greater exposure. So that's why we designed it to tap into that number, so based on that data. But we do that with about half of the injections of lebrikizumab. So we get the exposure benefit because of that optimized PK, PK profile without having to take a hit in terms of injection burden for patients. We have a benefit in terms of injection burden. So, you know, really excited to read out that data. I think a win for us is equal data, equal induction data to Lebri and Dupi in the induction setting with that less frequent dosing. But also happy and excited to be testing this hypothesis of whether additional exposures can give us additional benefits for patients, and that can mean a lot of things- ... not only top-line numbers, but decrease in flares, you know, and decrease in itch, other things that it could be beneficial for as well. Yeah, great, great, and you anticipated a lot of my follow-up questions. So I do wanna ask one more 777 question on the commercial front, before we move on to the rest of the pipeline, 'cause there's a lot going on. I guess you alluded to this, Carl, too, lebrikizumab finally approved in the U.S. I guess maybe, Jeff, like, what are your thoughts on, on the launch and the potential readthrough to Apogee, and just in general, how the, how the field is evolving? Sure. Yeah, yeah, thanks, Alex. I think first and foremost, we expect, because this market is so underserved and unsatisfied, that Lilly will have a good launch here. I think, if you look at ex U.S., that kind of guides us toward that as well. For example, Germany and the NBRXs, that we see early on. I think secondly is when you look at this market as a whole, you know, the penetration is so soft, looking at biologics. Yeah, and this is a huge market, right, Alex? We're talking about 3x the size of plaque psoriasis. So I fully expect that Lilly will have a solid launch here. I fully expect that it will continue to drive more patients from topical corticosteroids over into the biologic space, but there is a long way to go, as this is so unsatisfied, and that is exactly why, you know, some of these changes that are being made, if you look at the dosing alone, the patients, physicians, everyone has a desire, need, and a want for a better solution. Yep. Yeah, and there's obviously so much more we could talk about, but also so much more to cover, and so I wanna transition to 808. And, you know, specifically, you know, why this is an exciting molecule versus dupilumab, and I guess maybe your rationale for going after respiratory and COPD here. Maybe, I don't know, who wants to start? Michael? Would love to. So why is it an exciting molecule versus Dupilumab? Dupilumab is a great antibody. But again, right, it's dosed every two weeks and right has a lot of liabilities. So what we did here is we actually have a femtomolar antibody, so right, Dupi's great, it's picomolar, but femtomolar is a higher affinity binder. And you can see that across all of our assays, that it does translate to improvements across a number of preclinical assays. And at least preclinically, right, we have over 2x a half-life of Dupixent. We're looking here, because we are starting from a shorter half-life, a lower base of Dupi's 15 days in the clinic, to get to 40 days or above. That would get us from an every-two-week paradigm with Dupixent to an every six-to-eight-week paradigm. When we looked at where to position this, we kind of found ourselves with just almost an embarrassment of riches, right, to be frank, with having an every three-to-six-month drug with 777 for atopic derm. We thought, "Where could every six-to-eight weeks still be quite meaningful?" COPD was the clear answer. Right there, you have an every two-week drug that's soon to be approved, hopefully, in the U.S. for COPD, and that's all with TSLP, of course, coming in years from now on the horizon. And we also added a TSLP ahead of that, seeing that that could happen. So, the unmet need in COPD was kind of the clear rationale. Yeah, I guess, you know, to that expansion point, you know, what is the COPD launch gonna look like for Dupixent, and what are you looking for, hopefully, you know, later this year for that launch to get started? Yeah, I think it'll be, you know, when we talk to different pulmonologists and folks that are waiting for that approval in the USA, right, there's just nothing for these patients, and this is a disease which can kill you and, right, leads to hospitalizations, and there's been a clear signal, you know, repeatedly in their trials, so you know, Jeff, you're welcome to add anything, but I think we're optimistic that Sanofi and Regeneron's bullish statements are merited. One thing I would add is that, you know, likely they'll have line extensions from, you know, their AD indication that will allow them to get a quick uptake in the market. And so the path forward for this, you're gonna have phase I data later this year, and then can you lay out kind of the next twelve months or so for this molecule? Yeah, so our phase I data end of the year, we're then launching a phase Ib in asthmatic patients as well. And we're doing that because we want to show some activity on FeNO, which we think is a strong surrogate biomarker and has now been linked to both FEV1 and exacerbation endpoints in later trials. That will help us to refine and validate the dose that we could then take into COPD next year. I think, right, and we touched on this briefly, we did add TSLP- Yeah... earlier in the year around the data announcement, and we did that not knowing how the Phase 1 data would read out, but also thinking that when we look at respiratory indications, we actually don't see the exposure response evidence that we see in atopic derm in many of these respiratory indications. So for us, always wanting to have a best-in-class drug in terms of efficacy and dosing, we added TSLP so that we could also pursue combination approaches, either with 808 plus TSLP or IL-13 plus TSLP. And we just need more data, both ourselves and externally, to help know what would be the optimal TPP to take forward. Yeah, and you know, with your combination platform, you also have your OX40 ligand target. Can you talk about why that makes sense as sort of another foundation for combination as you think about expanding beyond Th2 targeting? Yep, I'll start, and then Carl, please, add on. Like, when we look at just what has worked in atopic derm historically, there are only two mechanisms that have ever worked in phase II trials, for atopic derm. That is IL-13/IL-4 and OX40 ligand. Outside of that, everything else has tried, but not kind of passed the bar in a phase IIb trial. And when we look at what OX40 ligand does, it hits three types of inflammation, right? Type 2, of course, just like IL-13, but also Type 1 and 3. So it's the ideal, optimal orthogonal target to combine with IL-13 to hit all the drivers that exist, including the heterogeneous drivers, which sometimes, lead some patients to not respond. Carl, did I speak to add on there? Yeah. No, just to kind of add on to those points, right? Just, you know, I mostly said it maybe a little different way, right? Which is, we know that IL-13 is the key or main driver in all of atopic dermatitis, right? So if you look at IL-13 levels, whether it be in the skin or peripheral blood, right, it's somewhere between 10-30x greater in patients with atopic dermatitis compared to, you know, healthy or non-atopic dermatitis patients, right? And so, you know, that is the thing driving that, and I think the depth of response you see with lebrikizumab, especially in Dupixent as well, right, shows that that is the key piece in driving yeah, atopic dermatitis. That said, we know that it's a very heterogeneous disease, Type 1 inflammation, like interferon gamma, et cetera. Type 3 inflammation, like, IL-22, et cetera, also are contributors here, especially in some populations, whether they be, you know, ethnicity-based or age-based or chronicity-based, meaning chronic patients have a little different cytokine makeup as well, too. And something that is missing when you're only targeting that single thing, right, is grabbing at the rest of that cytokine milieu. Something that JAKs have done really well, right? They hit all of those types of inflammation. They probably hit them too hard, which has led to the safety liabilities associated with them. So what we're trying to do is increase the efficacy bar with what we know has worked well, IL-13, and then secondarily, OX40, OX40L, and get to a better, you know, depth of response, that similar depth of response for IL-13, but some of the breadth of response without going too broad, like JAKs, right? We think that balance is really by doing IL-13, OX40L together, orthogonally validated mechanisms that have shown really great data and really will combine that, both that depth and breadth of response with the right balance in it that we need to move forward and really provide transformative care for patients with AD. Yeah, obviously a lot going on here, and I know you're also gonna have a R&D Day later this year. So maybe, you know, what can you say about what we should expect coming out of the R&D Day around some of the next steps across, you know, your pretty wide and deep pipeline at this point? Yep. So, you can expect that we'll provide updates across each program, at that R&D Day. I think it's important for us to try to highlight the company's totality and, right, the number of kind of blockbuster drugs that we have in our arsenal. The data underlying our conviction, not only for the monotherapies, but for these combinations, right? We can, you know, tell you why we think that they're optimal combos. We'll put out data, showing, you know, how they compare to monotherapy benchmarks, including, right, the Dupilumab, et cetera, so you can see, what's getting us so excited about them, and we'll also, you know, share some more around the trial designs for the combinations, right? And people do not realize that our IL-13, OX40 ligand combination will start next year. That is, we will have the first-in-class combo AD kicking off very soon, and we'll share more around what that trial is gonna look like and when people can expect that data as well. Great. Always a great conversation. We probably could spend another two hours chatting, so gonna cut off there, but always appreciate you guys. Thanks for joining us. Yeah, thank you, Alex. Thanks a lot, Alex. Bye, everyone.