I think we'll, I think we'll get started. Day three, London Healthcare Conference. It's been, it's been a lot of fun. The weather's been actually decent. It rained a little, but otherwise I think we're good. My name's Akash Shah. I'm a pharma and biotech research analyst here at Jefferies. I have the Apogee management team. Big year, 2026 for, for the company, so it's gonna be an exciting conversation. Why don't I hand it off to Mike for intro remarks, and we'll get started. Yeah, I appreciate it. Thank you all for attending, and for the invitation to the conference. Absolutely. It gets better and better every year. Weather too, actually, weirdly. Weather too. Yeah, as Akash alluded to, very big year for us in 2026. Earlier this year we put out proof of concept data for our lead drug in atopic dermatitis. We followed that up with data showing that not only is it great on lesions, but it's also rapid on itch relief by 48 hours. That has translated into a lot of enthusiasm from docs into our studies, which has allowed us to accelerate some of those readouts coming next year. As we head into next year, four clinical readouts, which I'm sure we'll get into, all of which we think have the potential to cement our place as having the future frontline drug of choice in atopic derm with our monotherapy, dosed every three to six months. Full pipeline of product potential with asthma reading out alongside that maintenance data in Q1. We'll have an optimized dose in Q2 with our part B, which allows us to kick off phase IIIs next year, launching in 2029. Our combination study will be the second line drug of choice, we believe, IL-13, OX40 Ligand. We're running that head-to-head versus Dupixent, looking for an 8-10-point improvement in efficacy to then take that forward into later stage studies. Very big year. Mm-hmm. Fortunate to have a strong balance sheet headed into it so that we can grow value appropriately. Understood. You know, I'm gonna start off, kind of with a different angle here, and I think it's important. You know, I cover Pfizer, and you know, obviously it's rare to see takeouts in obesity, and it's rare to see also come two giants bid up. We're seeing that a bit more in this market. You know, it's funny. I think a lot of people miss Metsera, including me. I looked at it and said, "Okay, it's a long-acting GLP-1. There's a long-acting amylin. There's a lot of those drugs out there. It's long-acting, but what else are we, what are we missing here? You know, when I was actually forced to look at the asset itself when, you know, Pfizer did the deal, I suddenly had a realization, you know, to replicate that, you would have to do three different transactions, see if the co-formulations play well with each other. Jane, I want you to chime in. Here is also, like, to be quote-unquote fully paid for, to actually spend the capital out of the gate to have a program that a pharma company can actually take and commercialize relatively easily. That's a framework that's hard for a spin cap company to take. It's a mature perspective. I think there, I certainly think there's probably read across as to what your team is doing with Apogee. Can you talk about the read across you see with Metsera and the strategic value you saw there and how it might even apply for an orthog, a different indication entirely in INI? Yeah. Appreciate the question. I think, right, know, know Wit well and kind of the team there. We chatted historically just because very similar approaches, right, longer-acting antibodies, with the ability to combine. To your point, especially that middle point, the hard thing is it's really hard to go and buy three, four different antibodies off of different platforms and co-formulate them. In fact, it's incredibly unlikely off of those different platforms that they will be able to be co-formulated. Mm-hmm. At a reasonable concentration. You'll just be limited, right? From the very beginning, we've been very deliberate about having not just a monotherapy strategy, but an atopic derm strategy, right? How can we look at all the science that's coming and position ourselves to win in each line of therapy for each pocket of patients? Because there are just so many patients and so much unmet need in the space. When you think about, you know, the companies that have really done this well, I think Pfizer with Metsera obviously are taking that approach. If you look at Vertex, right, and cystic fibrosis, Gilead and HIV, they are the companies that look to not just have a play, but keep improving upon themselves and set themselves up to have the winner and a set of winners to really provide the most options for patients. In terms of kind of capital outlay and the benefits there, please, Jane. Yeah. We are being very disciplined and looking for the signal in a 1B, of our combo versus Dupi. Why go all the way to and wait for a phase II to answer that question? Mm-hmm. From a capital deployment across the portfolio, but including the combo, a 50-patient trial of 279, versus Dupi, and we'll look for 8-10 points greater in the various efficacy endpoints and have that single signal early before we would go into a larger phase II contribution of parts. Understood. Actually, let's put it this way, 'cause again, sometimes the critique we'll hear is, "Well, people can do this," but then at the same time, if you do the heavy lift on showing contribution of components, Jane, there's a real financial cost associated with that, which I think is valuable in and of itself. Talk to me about it, and Michael, like, how expensive is it to actually run across multiple trials contribution of components with different mechanisms of action? And A, when do you think you're gonna satisfy that from a regulatory perspective, but also just the cost associated with getting that done? Yeah. Carl, do you wanna maybe speak to just the. That's fine. The regulatory piece, and then Jane, you can weigh in on the cost side. Sure. Yeah. No, happy to, right? I think that, you know, the, I guess I'll say the main disadvantage of our approach, right, which is, fixed dose combination, is that you have to do contribution of components at some point in time for, for regulatory requirements. So showing that the combo is better than the individual agents. You know, one, I think that, we've heard a variety of things on how much that takes, right? We think that the best place to do it is in phase II trials, right? We wanna prove that, earlier rather than later. We're even bringing that back in to de-risk that, contribution of component study by, going head-to-head, versus Dupi, right? Mm-hmm. While from a regulatory perspective, we need to do that, you know, I think from a KOL adoption standpoint and potentially even a payer standpoint, whether you're going after multi-targeted agents through a fixed dose combo like we're doing or through a bispecific, people wanna see that multi-targeting is better than single agents. There is no version of this where you do a bispec and you do not prove that and you actually get used early on in treatment, right? If you're only showing you're better than placebo, docs wanna know, "Well, why would I give two things which has, you know, potentially more risk if you haven't proved to me that you're better than Dupi or you're better than an IL-13, et cetera?" I think everyone has to do not contribution of components, but showing they're better than monotherapies if they wanna be not regulated to third, fourth, or fifth line regardless of the approach. We think, you know, in a phase II, right, we'll add two extra arms essentially to that. Say 100 patients per arm, and I'll let, you know, Jane comment on that. It's not this crazy absurd number to add to it. I just add, just 'cause I said the downsides to our approach, the upsides are so much more, right? One is we get to, you know, continue to move and advance the AD landscape in terms of dosing intervals, right, with our approach 279 and our recent data, TSLP looking at 273, which is 777 and 333 combo, for respiratory. You know, we think we can get to at least every three-month dosing. That might not be true for bispecs, which we've really only seen short half-lives for. Mm-hmm. Finally, right, we're trying to prove that we're better here than, than monotherapies. To do that, you really need to optimize the exposures of both drugs, right? The only way to do that and to optimize the ratio is to do fixed dose combo. Otherwise, you're doing one-to-one targeting, which we know is probably suboptimal for all the combos people are looking at. Also, a benefit from the co-formulation is the ability to extend the half-life further, as well as we anticipate low single-digit COGS for a co-formulation. Bispecs tend to be higher. Also, you tend to see some ADA rates with bispecs that we have not seen on the co-forms. From a cost point of view, as you are looking at a phase II global trial, we estimate, per patient, it is about $250,000 per patient to run that phase II trial. The incremental 100 patients. We go into a phase III that is the same as any other phase III. Mm-hmm. which is the two replicate phase III trials for filing. Understood. Now, maybe stepping back and, you know, as, marketing in Europe, before the conference, and, you know, we're starting to see hints of even on the bispecific side in atopic dermatitis, potentially 1 + 1 might actually equal 2. I think that gets kind of interesting. I know UCB has some compounds. They have an IL-13, IL-17. Mm-hmm. You know, T2 dendritic cells. They also have an IL-22. And it does seem like, you know, that management team is optimistic that there might be an additive benefit with, you know, you know, these two kind of known targets, one like IL-22, which actually was failed. You might actually see an improvement on efficacy. First of all, you know, does that surprise you with those targets? And then when you think about, you know, your target selection. Mm-hmm. you know, IL-13 or OX40, why did you pick them? And why, you know, why are co why could there be orthogonal biology and additive benefits in a way that maybe the street doesn't really appreciate right now? Yeah. No, I think we're excited to see signs of, right, signs of life and signs of kind of incremental data. I think we need to see a lot more from emerging combos, right? Currently with the UCB, it's, right, it's an IV dose. IV, you get high exposures. There's high exposures of IL-13, inherent in that. So I think part of it is we believe there is an exposure response with IL-13. Sure. It, to kind of the points that were made, I think it's, it could be a really exciting drug for later in line patients. Are we going to then take a step backwards to monthly dosing, every two to four-week dosing just with those compounds? For Psoriasiform AD patients, right, IL-13, 17 could be interesting. For, you know, more like kinetized skin, IL-13, IL-22 could be interesting. For itch patients that like Nemo but don't get lesion benefit from NEMLUVIO, right, maybe an IL-431 could be interesting. Those are all, I think, subsets of a second line market, which are exciting, right? 777 is, I believe, will become the front line drug of choice. Still, there's a third of patients that even on 777 by week 16 are not getting to 75% clearance. Currently, you know, there's only JAKs Right. There's a lot of room for this to develop like the psoriasis space has. When we look at why we chose our targets that we did, IL-13 just has the best data as a monotherapy in biologics. Sure. Right? Ebglyss looked similar, slightly better than Dupixent. Our data we've taken into docs, right? You've, you've spoken to those KOLs and looked at the data, right? We're as good or better across endpoints. EASI-75 in particular, we're quite proud of the, you know, highest absolute and placebo adjusted data to date. It's a very heterogeneous disease though. It's not just 17 or just 22 or just 31, but a component of these different drivers. Mm-hmm. In addition to IL-13 that drive disease. The best data to date, albeit right, not hitting the bar that I think people would hope for, is OX40 ligand. It still has the best lesion data. When you look at the phase II B, what's really interesting is you see decreases in IL-17. Right. You see decreases in IL-22, decreases in IL-31, decreases in TNF alpha, decreases in interferon gamma. It is by combining that deep type two IL-13 inhibition, which is only partial with Amlodelam and OX40L, with the broad inhibition that you get across these, you know, kind of escape, you know, passenger almost pathways of inflammation, we're looking to replicate the success that JAKs have seen without the safety liabilities. Mm-hmm. 'Cause JAKs also hit all types of inflammation. Right. You have, you know, 20 points -25 points better efficacy across every endpoint. Rooting for them because we're also seeing, and this is remarkable, it's remarkable to see playing out live, even though history suggests that this always happens. There's only 10% penetration right now in a biologically eligible atopic derm. Dupixent is growing faster with new players entering. Mm-hmm. Right? This is not a zero-sum game. As NEMLUVIO has launched, as Ebglyss has launched, NBRX has gone from 20% to 49% in three quarters. It's never been growing faster, even as those drugs are taking off. Right. More patients need more treatments, and patients need the ability to start on whatever they want to from a, you know, dosing and adherence point of view. If that is not their solution, even a 5%-10% portion of a second line market can still be a blockbuster given the size of this. Understood. Now, I think maybe stepping back, and, you know, it's interesting in INI, there's always like the bet I, you know, and we've had this conversation, the bet I want to make in two randomized well-controlled phase III studies versus the bet we're going to see on, you know, early phase one data. It's interesting, three times in your period of remarks, you, you know, your team talked about 8%-10%. Mm-hmm. You're comfortable with that, standard you're setting out in terms of the combo. To me, what's very provocative is I could see an 8%-10% delta in a phase II study and say that's superiority in a well-controlled phase III trial. Mm-hmm. Let's get into maybe the nuance here. There are a couple. A, when you talk about 8%-10% delta, tell me about what the endpoints, 'cause I think that also becomes, how do you define it, placebo adjusted? Are you comfortable with that bar in a 16-week combination study with the end you're gonna have next year? 'Cause you have a big readout with Dupixent as one of the arms. I just want to make sure we have that level set. Yeah. Right, we're running a head-to-head trial versus Dupixent. 8%-10% across one or more endpoints is what docs tell us is the bar. Payers say this as well, right? Patients, I think, see this as meaningful enough activity to try this agent if they do not respond to a front line agent. Mm-hmm. That can come in a variety of forms. JAKs were 20-25 percentage points better across EASI-75, EASI-90, and IGA01, right? We are looking to replicate JAK biology without the safety liabilities. Mm-hmm. Getting, you know, to your point that you started with, one plus one might equal two. We really need one point one to equal one point two. Yeah. 1.3. Right, JAKs equal 1.5. Right. If we can march our way up there, then that's the bar that we know is convincing to physicians and patients and payers. Also, the bar to the point that Carl and Jane made earlier that we can fairly comfortably power for in a phase II- B contribution of component study. It starts to get very manageable around that. It isn't, this trial is not powered. Yeah. Currently for a P-value or superiority because, like JAKs, we don't yet know before they ran their studies where the greatest delta would be. It could come in the form of all endpoints, or it could come in the form of an EC90 and IGA. Yeah. Deeper response. It could be a higher EASI-75, or maybe it is at week 24 for some endpoints and at week 16 for others. I think there are a lot of ways to win by running this study and just generating a very rich data set versus Dupixent. I think that's spot on. Actually, there's an element to this, and I was talking about this with Carl at SPIRE. A lot of times when we go into maintenance, you know, like you're hoping we can sustain efficacy. You know, certainly with the shorter half-life drugs, that's the hope is you kind of nuke the target, you get the disease under control, space out dosing as much as you can. Mm-hmm. I feel like you do not really have to make that decision here because you would be able to get sustained blockade while also having a pretty wide dosing interval. To me, also overlay that with OX40, look, I get it, it did not hit the Dupi data, but, and Carl, I am curious how you think about it. The trend was up. Mm-hmm. Sanofi talks about that too. It's like there's a deepening of response that actually happens with OX40 that I don't think, like, does it really matter if it's in the, you know, phase III clinical trial or does it actually manifest in the maintenance? You know, let's put it two ways. One, you have a maintenance data in IL-13 that's coming up. Yep. How do you think about the bar there? What do you wanna show to get your team excited? Number two, when you think about the combo efficacy where it could really start to shine, is it at 16 weeks? Is it at 24 weeks? Or maybe we should wait to 48 weeks, which is when you're gonna have, you know, the phase III endpoints and the time points you're actually gonna be looking at. Yeah. I'll start maybe on the first question and hand it to Carl for the harder question. For the first question in IL-13 maintenance, the bar that we hear from docs is the last piece of the data trifecta that they wanna see is every three-month dosing. Mm-hmm. Right? We have deep lesion control similar to or better than Dupixent. We have rapid itch response faster than Dupixent, similar to NEMLUVIO. Now they wanna see that SKYRIZI-like dosing. That's defined as percent of patients that had achieved EASI-75 at week 16 that have maintained that through the full year at week 52. For Dupi, that's 72% EASI-75 maintenance, 53% IGA01. That is, I think, a fairly clear bar that we will compare our three and six-month dosing against. What I think docs are curious about is similar to amlitelimab actually. A few have noted our curves have not flattened by week 16. Some of our curves are still trending. They wanna see is there deepening 'cause there's not with Dupixent. Week 16 is interesting, but that is also a, like, none of us live our lives in week 16 increments. This is true. It's about how you do over time. Sure. I think we wanna see every three months. Our intention is to learn from this data set to inform the dosing to take forward 'cause we wanna take forward into the phase III. Every three and every six month, we wanna make both available. That is what physicians want as well, that optionality. We're excited to turn that card over in Q1. That's actually the readout that docs are probably most excited about. Interesting. Oh, for us next year 'cause it's the unknown in their mind. They have a sense of part A induction. They know that there's, you know, they wanna see that replicated. They wanna see the higher dose to know, but they now wanna know that there's durability 'cause they haven't seen a long-acting antibody. They wanna just, they're excited to see it proven out 'cause they've seen the power of that with SKYRIZI. In terms of the second question, I'll hand it to Carl. Yeah. On the second question, right, combo efficacy here, right? I think that, you know, first thing is I do think, you know, the Amly data is quite interesting, right? We have an OX40 also. I think I have to say that. Just, you know, the initial part is quite slow, right? Not much is happening in that first eight weeks or so. The biology would tell you that's probably what you would expect, right? It's trying to, like, you're changing underlying T cell populations, and that's not a one or two week effect, right? When we talk to docs, what they say though is like, how do I get patients through 8 to 12 weeks before I start to see some signs of efficacy here? One of the things they're excited about this combination, in addition to what Michael said, which is deep type two inhibition with IL-13 and broad inhibition with OX40L, is they also get a faster response with 777 in that early week. You are getting patients. Right. To the ability to respond deeper, you know, on the week 16, you know, versus 24, you know, right? We don't live on a, you know, 16-week clock, right? I guess here. That's getting away from this. Here we live on a bell at 25 minutes, which we have three minutes till the bell comes, right? I think if you're not seeing signs of that by 16 weeks, again. Mm-hmm. Are you gonna have people wait six months or a year to have a little better response than they would've had on a monotherapy alone? Probably not. Will we see the maximum delta from Dupi at 16 weeks? I don't know. I don't think we have to see the maximum delta we ever see, but I think we have to see a delta at that 16-week time point to have people convinced that we're leading towards something that they can really give to a patient and say, "This is gonna get you better than doing monotherapy alone too. What's, I think that's a really important point. When we think about that, okay, so if, let to be clear, 8-10 is for a 48-week endpoint, or is it for a 16 or 24-week endpoint? And if we were gonna adapt it again to that 16-week. Yeah. Should we say, "Okay, maybe not 8 - 10, but we should be thinking like six points or something like that"? Help me understand the temporal aspect of, you know, efficacy kind of deepening. Yeah. I mean, I think you have to see 8-10 by 24 weeks at the latest, right? I mean, six months is a clock 'cause we're talking about clocks a lot in this, in this fireside, is a clock that, like, docs live on, right? 'Cause you're not coming in at four months. You're coming in at three months and six months, right? I think that is something that, right, you come in by six months and you're seeing that change by then, right? Could deepen over the time, right? It needs to happen by then too. It might be a few points less than that at 16. The other piece, which, we haven't talked about this, but you will, you will find this tantalizing, is after six months, we take everyone off drug, both arms, and we see how long remittance is in effect. Mm-hmm. After administration of both. I think that will be an additional data point, which people will find, well, we're excited to see how it looks, and docs are very curious about, right, can there be a remit of nature to this as well? Understood. Maybe lastly, RESPI, 'cause I, look, that's a part of your story. I don't think you got enough questions on. Mm-hmm. Sanofi does have their own kind of bi-specific readouts that are coming up. Again, like, I think right now we're also in that place where I'm not sure one plus one equals one too, 'cause you don't know if, you know, the bi-specifics are leading to better phenol reduction. What do you expect from the Sanofi bi-specific when it comes to asthma and COPD? Do you think there will be an additive benefit? And then number two, how important is your respiratory portfolio to the broader strategy kind of for Apogee? I know we talk a lot about atopic derm, but, you know, why is RESPI maybe just as important? Yeah. Right here we're building a, a type 2 inflammatory company. With OX40L, right, we have the ability to kind of go into type 1 inflammation as well. It is an extension into broader inflammation. I feel with TSLP, it's the same, right? It's the ability to get out of that EOs greater than 150 population and into all-comer asthma. Okay. No biomarker at all. The LinseccaMig data from Sanofi isn't in all-comer asthma. I think that'll help to show it should work. TSLP works in all-comer asthma. Mm-hmm. Right? Dupixent worked in eosinophils that were lower. It just was not as strong. Right. Not as good as other monotherapies. Still, maybe 1 plus 0.5 will be equal to greater than 1. Yeah. In that case. We're excited to now have unlocked quarterly dosing or better for our respiratory approach with Sanofi's data coming for lunsekimig in asthma. They've now started COPD and other studies. We're very excited to see how that reads out across, right, AER. Does it improve upon monotherapies? How does it look versus monotherapies by different subcuts of the eosinophil population? Mm-hmm. It can win by depth, but also breadth and depth could be, could be a home run. It is an every, it is a 9-11 day half-life drug. Significant advantage to improve on dosing. Understood. We are out of time. Hey, thank you so much. Really fascinating conversation. I really do appreciate it. Thanks so much.