Okay, great. So good afternoon, everyone, and thanks very much for joining us for another fireside chat discussion here at Guggenheim's inaugural Healthcare Innovation Conference here in Boston. I'm Seamus Fernandez, one of the senior biopharma analysts here at Guggenheim. Really pleased to be joined by several members of the Apogee team. Apogee Therapeutics is actually a Guggenheim Best Idea, sort of an unusual moniker that we place on the stocks that we have the highest conviction in in terms of the sort of year-over-year performance. And that's our Best Idea for 2025. So a lot coming for Apogee in 2025. I'm really pleased to be joined, and I'm going to go from my immediate left to right. Carl Dambkowski, the Chief Medical Officer, my immediate left. Jane Henderson, who is to his left, Chief Financial Officer. And Jeff Hartness, the Chief Commercial Officer, to Jane's left. So again, everybody, thanks so much for joining us here today. We're certainly excited about the opportunity that we see ahead for Apogee in the market. But maybe just to, Carl, just to sort of start off, maybe talk a little bit about the core of Apogee's strategy with regard to the TH2 marketplace in particular. Yeah, no, happy to. And thanks for having us here. It's been a great conference so far and excited for this chat too. So as we look at what we're doing, I think the core piece of the thesis is optimized antibodies targeting known and clinically validated targets for inflammatory conditions and specifically the TH2 pathway broadly. And then I think further subdividing that into best-in-class monotherapies followed by best-in-class combination approaches. So I think our atopic dermatitis development plans really kind of show what we're doing overall, which is we're moving forward right now with APG777, which is an optimized antibody for IL-13. It's in a phase II trial of atopic dermatitis right now, reading out second half of next year. But we don't just see that as the only potential there. We're also pursuing combination approaches in atopic dermatitis as well. And for that indication, we really see we have three shots on goal in terms of improving efficacy overall, in addition to, I think, the easier part or the more obvious part of the story, which is improved dosing frequency or improved dose injection burden for patients. And we're looking at every 3-month to 6-month dosing intervals with APG777, but not just stopping there, looking at the potential in our Part A data, reading out second half of next year to increase efficacy with 30%-40% greater exposures compared to lebrikizumab. In our Part B study for APG777, further optimizing the dose beyond that. And then next year, starting combinations with APG777 or IL-13 and APG990 or OX40L to continue to increase the efficacy bar too. So multiple ways in terms of taking our optimized antibodies and looking for not only best-in-class dosing, but best-in-class efficacy. We have multiple ways to win in that. AD is one example, but we're also doing something similar in respiratory as well. Jane and Jeff, if you wouldn't mind answering a little bit of what you see as the market opportunity, specifically, one, the compelling nature of this disease state and the desire that payers would have to sort of support a new group of agents, but also just sort of the expansiveness of the market opportunity. Yeah, thanks, Seamus. I appreciate the question. That is the question because the first indication that we're diving into, atopic dermatitis, it happens to be the largest I&I indication, and it also has a very low biologic penetration, so the opportunity is incredible. When you look at that and you couple that with what's available for patients today, frankly, there's quite a bit of white space in AD. If you look at plaque psoriasis, they have something like 12 biologics now on the market. AD, really, you're talking about the two with the best efficacy, Dupixent and Ebglyss. Both are dosed every two weeks or two to four weeks, so the reality is AD patients need better options. And we believe that Triple Seven allows us to bring forward differentiated and innovative dosing, number one, every three to six months. To Carl's point, we have multiple chances at better efficacy as well. So from a payer perspective, to answer your question, Seamus, we've done quite a bit of market research already. We're seeing that payers see the value in this space. They know that it is large and growing. This is going to be a $50 billion a year market. We see that in early market research that we would be a first-line biologic equal to Dupixent. So I think that payers will see and do see the value in new innovative products coming to market for these patients. Beyond AD, we see very large opportunities in asthma and COPD as well. They are also very low penetrated compared to psoriasis and others. And Carl, I think to Jane's point, we're also seeing that TH2 disease is a bit more expansive even than that. We're starting to see GI disorders emerge. How broadly do you think the Apogee portfolio can actually reach into other areas? We've seen some efficacy in EoE with another IL-13. How do you think about the expansiveness of the opportunity? Yeah, I mean, I think we're realizing that TH2 is a key driver of multiple disease states, as you say. Some, it's the primary driver, like AD. And others, we're learning how to phenotype patients to understand where we can have the greatest benefit too. So an example, and this hasn't read out, but Dupi's even in an IBD study with high eosinophilic IBD. And so the potential is really broad. I think how we think about it just in terms of portfolio development overall is there's three broad therapeutic areas that we can go into: derm, respiratory, and GI disorders, all with IL-13 or IL-13 related combinations. And then below each of those, we'll look at both primary indications and secondary. Obviously, for derm, that's AD. For respiratory, that's asthma. For GI, I think more to come in coming months and years on exactly how we're thinking about that. But as we get the cornerstone indication behind each therapeutic area, then we'll continue to expand beyond that as well too and harness what we learn from that first indication, both about dose optimization, et cetera, and hopefully use that to propel the subsequent indications by TA more rapidly. And we've seen Dupi do a really good job of this too. They did an example, their dose finding in AD, but didn't necessarily replicate that for PN and BP, both derm indications too. They just went straight into phase IIIs for that. Similarly, for respiratory, they did dose finding in asthma and then just went straight into phase IIIs for COPD and other indications as well too. So we'll take a little bit of what they've done in terms of their playbook, but try to expand on that. And something we're always focused on is the operational excellence that comes with moving quickly to these indications to give patients really meaningful drugs. So, talk about the selection of IL-13 as a backbone agent across your portfolio. I think that's a really important point. And are there opportunities to show beyond just dosing? Are there opportunities to show efficacy superiority and/or safety differentiation from your perspective in any of those disease states? Yeah. Yeah, so great question. Hopefully, as people know right now, APG777 is our lead program. It targets IL-13 in a similar manner to lebrikizumab, which has really shown best-in-class data probably for AD in general, but definitely for IL-13 targeting agents, but data we put out earlier this year from our phase I study, which shows a 75-day half-life compared to lebrikizumab, which is kind of 23- 24 days, and the potential to get to every 3-month to 6-month dosing, which we're testing in the clinic right now. I think a couple of things that really set that as our backbone of how we see going forward and expanding. One is the data that we've seen so far and the potential for every 3-month to 6-month dosing, which compared to Dupi and Lebri, is up to a 13-fold decrease in the injection burden for patients overall. And then the second piece, and I think this is especially related to AD. What we've seen with lebrikizumab data is not only the potential to match in terms of their efficacy, but multiple sources of data saying that there's potential efficacy left on the table with that mechanism. So specifically, we see three sources of data that allow us to, or at least have us move forward with a hypothesis that additional exposures could lead to better efficacy in atopic dermatitis. One is their phase IIb study, which showed a really nice dose-response relationship, never really plateaued that efficacy response, probably because they didn't want to go to weekly dosing and be disadvantaged from Dupixent. So that was an unknown. And then two more recent sources of data from their approvals showing that higher exposures could potentially lead to better efficacy. One is there was a weight efficacy relationship. The lowest weight individuals on lebrikizumab had the greatest efficacy. And that matters because that group had about 30% greater exposures compared to the general population involved there. And that's what set our target for APG777 in our phase II trial of 30%-40% greater exposures. And it's not just two or three points of better efficacy across all key endpoints that were shown in the approval documents, about 5-10 percentage points of better efficacy, even on the most stringent endpoints of EASI-90 and IGA 0/1. And then finally, there's an exposure response model within those documents too. And when you recreate it, it does suggest that there could still be efficacy left on the table. So it's twofold why this has really become kind of the backbone. One is the potential based on our phase I data for every 3-month to 6-month dosing, which is really transformative for the atopic dermatitis space. And the second is that it's potentially not just a dosing play. It has the potential for better efficacy too. And then we see that also being a great backbone for combinations, our first one being APG777 and APG990 in atopic dermatitis, looking at IL-13 and OX40L together. You brought up OX40L and that trial, at least the initial trial is underway. Can you just remind us the timeline for when the sort of single agent, maybe not efficacy, but the single agent sort of PK, PD data is going to be available? And then separately, how do you think about this debate over OX40L versus the OX40 receptor targeting agents? And there's a lot of different ways to target the receptor. I'm going to limit it just to the rocatinlimab phase III data because we have that. Yeah. Fair point. So first, just on where we are right now, so APG990, which is our OX40L, extended half-life OX40L into the clinic in August, one month away, August of this year. And so we'll put out PK data for the first half of 2025 on that program. And then, as I mentioned a couple of times, move into a combination study of APG777 and APG990 in AD patients in 2025. We specifically chose the ligand. And from the very beginning, we've been interested in OX40, OX40L because of its combination potential. I think what we've seen in the data thus far, whether we look at OX40 or OX40L, and I will get to the debate on those too, is good, but not great efficacy. They just don't seem to match the efficacy that Lebri and Dupi have shown in the front line. That doesn't mean they don't have a space in AD. As Jeff said, wide open space here, very few effective agents that we've seen so far. But they don't seem to match the efficacy overall. And I think the reason for that is they get good broad suppression in terms of cytokines, type 1, type 2, and type 3, but not really deep on the key driver of TH2 or type 2 inflammation and IL-13 specifically. That's why we like it from a combination potential. We know AD is a heterogeneous disease. IL-13 is the key cytokine driving it, but is not the only driver, especially in subpopulations. So for us, we want to get deep inhibition of IL-13 through APG777 and then breadth of inhibition through an upstream approach of OX40L. And together, we think we can bring those together and lead to broader and deeper inhibition of key inflammatory pieces in AD. I think type 2-driven diseases have turned out to be much more heterogeneous than we've seen in other areas like RA or psoriasis, where you can get to a single driver and really push efficacy. I don't think we've seen that as much in type 2. So you need a broader approach overall. So that's kind of our hypothesis behind this combination and why we developed OX40L. Now, on the debate of OX40, OX40L, I think we're happy to be on the OX40L side of things. It's hard to say too much about rocatinlimab because Amgen didn't say too much about rocatinlimab. We don't know if the data from the phase III is related to baseline characteristics, if it's related to dose selected because they didn't really say anything about the dose selected, et cetera. It seems like they're still having similar rates of pyrexia and chills, which seems isolated to OX40 and maybe isolated to rocatinlimab as well, whether it's due to the ADCC component or not. I think we can stay out of that debate and say we know that OX40L has been very safe. Amgen put out a year and a half safety data, still looks very well tolerated and at least as good, if not better efficacy than rocatinlimab. So I think from the safety and efficacy standpoint, I think OX40L seems to be advantageous from what the data we're seeing from the two so far and excited to move forward PK data first, but then into the clinic with the combo as well. And in terms of the combo, do you see that as potentially sort of a fixed ratio first- line agent, or is it first- line agent is really 777, build the backbone, and then add on to that on top of it? I mean, I think we see it as a front- line agent. And our goal is to be developing it to get the efficacy needed to compete in the front line and with EASI-75 rates of 50% or so. I think there's still a lot of room there for front line. And nothing we see in terms of the AE profile of the two concern us with overlapping talks or anything like that. So assuming we get the safety we expect and can push the efficacy bar, I see no reason why it wouldn't be a first- line agent. Jeff, in terms of. Could we? Go ahead, please. Could we reach JAK-like efficacy with that combination? That would be the goal, but without the safety issues. The primary, when you say JAK-like efficacy, is it really attacking or going after the itch where we really see differentiation with the JAK? Or is it, again, when I look at the data, I kind of say, "Okay, the JAKs look maybe better on itch." It's very fast, that's for sure. The durability of it, I guess, it seems like Dupi can catch up over time, but just doesn't have that sort of amplitude in terms of the efficacy. Is that right? Am I thinking about it the right way, or is it? Yeah, right. I mean, if you look at high-dose Rinvoq, the itch response is within 72 hours of taking it. I don't think just biologically a biologic could ever get to that fast of itch reduction. So I don't think the speed at itch reduction is something that we can compete on in the first 72 hours just from it being a biologic. I just think it's not going to be that fast acting. But if you look at 16 weeks or even 24 weeks, Dupi gets better, but it never reaches Rinvoq levels of overall itch reduction or lesion reduction as well if we measure that by EASI-75 or IGA 0/1. So I do think there's still a place to continue to move there too through combination approaches, but not to discount, but I don't think 72-hour itch reduction is incredible. And so I don't think that is. But I think the safety trade-off there, sure, 72-hour itch reduction, but potential for all these safety issues. And when you think about the kind of typical patient on a JAK or with AD, moderate to severe AD, 30-40-year-old individuals, they don't want to worry about cardiovascular risk, malignancy risk, et cetera. And so I think they're willing to trade off some amount there if we can get to the efficacy advantage that we see. So you also announced today the TSLP is actually advancing more quickly into the clinic potentially as early as the end of this year or very early next year. Talk a little bit about the opportunity that you see for your TSLP, a longer-acting TSLP. There's been several that are out there. There are other potential competitors. How do you see your own 333 differentiating? Yeah, so I think similar to how we're thinking about APG990 in terms of APG333 really being an important combination player. So multiple long-acting TSLPs out there too. For us, we don't see this as a monotherapy play in general. We see it as an important piece, especially to our respiratory franchise in terms of combination approaches where we've seen TSLP be incredibly effective. And the potential for IL-13 TSLP combinations, I think the most promising area we can think of to develop a combination approach to improve efficacy and through our co-development or co-formulation approaches that we're taking still maintain that dosing advantage of every three to every six months. Given the breadth that we see of sort of the argument of an EOS lower efficacy with TSLP, why wouldn't TSLP be the backbone in pulmonary disease kind of taking the reverse of the potential approach with IL-13? Because I think IL-13, some would argue, well, we saw this data in asthma from lebrikizumab. Why might that thinking be wrong? That's a great question. So I don't think you gave us this in the prep questions, but one I would say, I'll defer to your first question. I'll answer the second, which is, you know, is lebrikizumab put out asthma data now years ago, right? The two phase III trials failed with them too, but I think if you really look at those trials, two reasons they failed. One is patient selection, which is probably the most important reason. The second is dose selection too. Those we both have control over, and in their patient selection, they chose an all-comers population with no history of exacerbations, both of which we know are incredibly important to designing positive trials here too, so as we go into APG777 monotherapy development in asthma, those are things we have control over in addition to our dose. Obviously, the optimized PK profile and optimized dosing is key to us. Then in the question of, I guess the question is, is 777 the backbone or is 333 the backbone? And I don't know the answer to that, I guess, in terms of that. I don't know if it matters though, right? If you put them together and you get better efficacy, we could call one the backbone or the other the backbone. I think probably it's more obvious in derm conditions where there's such a strong IL-13 drive that you're getting that. In respiratory, I think about it a little differently too, that the impact that IL-13 and TSLP are having on lungs is a little different. So it's not like one's the driver and the other is accessory, right? Because IL-13 is more central. So you're talking about it's leading to IL-13 increases are leading to mucus plugging, mucus production, things that are kind of at the lung level. And TSLP is more central, right? So that's like setting off this cascade of events that leads to an exacerbation. So different than our deep and broad is how I think about IL-13 and OX40L in AD. I think of this as central and peripheral in some ways, like controlling the inflammatory signals that come from the external environment to make sure an exacerbation doesn't happen. We control that through TSLP. And then the other side of things, the things in the lungs themselves that are setting off these exacerbations that are making patients feel terrible, have reduced lung volume, et cetera, that's IL-13 driven. So we're kind of preventing it at two different places here too. So a little different hypothesis. So that makes it less of a backbone, non-backbone, and they're just cutting off signal at two different places. It could be almost an even fixed ratio type approach. Yeah. That's why we like co-formulation, that we have optionality versus bispecific. Just to your question, we can make adjustments as we see fit. So Jeff brings up the great question of the approach to bispecific. The argument has been that we keep hearing is, well, the reason you'll bring a bispecific is that it's cheaper development. But what are the limitations of bispecifics in the context of long-acting treatment options and also that dynamic that we just talked about, fixed ratio combinations versus some more flexibility? Yeah. I mean, I think three broad benefits to co-formulation. One is dosing interval. We haven't really seen a bispecific go beyond Q4 week dosing. If even that, right, we can still get to every three-month and maybe every six-month dosing with co-formulation. Second is kind of the stoichiometry of this all. Bispecifics, you're forced into essentially one-to-one targeting, but we actually might want something like 3:1 or 2:1 or 1:1, right? But we can optimize that, and that optimizes the efficacy safety profile of these two. So we have that control over that, and we want to optimize efficacy and not just target two things simultaneously. So it allows the benefit for that. And then third is manufacturing or COGS-related, right? Yeah, I guess it's in some ways easier to do one thing. So we have to bring two forward, but the COGS are very complicated to manufacture bispecific. So long term, we have a benefit in terms of COGS too from this approach as well. Great. Well, unfortunately, we have to wrap up. I am going to just give one commercial. On December 2nd, you have your R&D Day, which will be very important, and it's a great opportunity to learn about the fulsome strategy and the overall profile. Anything, Jane, that you would share about it? Yeah, that'll be 10:00 A.M. Eastern. It'll be virtual, and we'll share the link here in the next couple of weeks. We're going to update across the pipeline. We're going to go deeper onto the combination strategy and some preclinical data. Jeff will be talking about some commercial topics. We'll have some KOLs, so we're very excited about the event.