It's the second day of the Citi Global Healthcare Conference. I'm Geoff Meacham. I'm the Senior Biopharma Analyst. My team here too, Nishant, Ross, Mary Kate. We're thrilled to have Apogee with us. We have Jane Henderson, CFO. We have Geoff Hartness, CCO. Guys, thanks for joining us. Good to see you. Thank you, Geoff. Good to see you as well. We have some questions, but I don't know if you want to kind of give maybe a quick summary, or do you want to get right into questions? It's totally up to you. I can give a very quick summary. First of all, thank you for having us. We're really pleased to be here and look forward to a robust discussion. 2026 is a transformative year of important clinical readouts for Apogee, and we're going to walk through each of those in our discussion today. Some of those we accelerated recently. So we have Q1 two data points for our lead program, 777 in AD. We have maintenance data. We also have asthma data for 777 in Q1. And then in Q2, we have our Part B, Phase II, where we're testing the dose response curve for 777 in AD. And then finally, in the second half, we have our combo trial of IL-13 and OX40 ligand, where we have Phase 1b ongoing and head-to-head against DUPI. An important year for us, and look forward to going through more details with you. Yeah, yeah. Well, Jane, let's talk about the initial 777 data. I think the positioning was match Dupixent and efficacy, similar tolerability, and then you have the better dosing profile. The only nuance of that, I think investors are past it now, but was the conjunctivitis. Maybe just give us some context for that, like why that's not a big deal. And looking forward, obviously, you guys, you're expanding the trial, and you're going to have data, more meaningful data next year. Sure, absolutely. So when we talk to physicians and KOLs, and they see our data from Part A, they say it's in line with real-world experience with Dupixent and with Ebglyss. What's interesting in trials now is investigators ask patients, "Do you have red eye?" When Dupi and Ebglyss trials were run, physicians would ask patients, "Are you feeling okay?" So certainly, it's now being looked for. They are typically mild and either resolve on their own, or they are treated with over-the-counter Visine. So as we talk to KOLs in our own market research and those that are done by Guidepoint and others, physicians do not see our conjunctivitis data to date as a reason why 777 would not be the biologic of choice all around that transformative dosing of every three and six months. Just a follow-up to that, when you talk to physicians in the community that have a lot of experience with DUPI, maybe what are some of the opportunities that you may have with 777? What are some of the pushbacks you get with, like, "Why don't you use more DUPI?" What's the sort of the theme in either discontinuations or underperforming patients that maybe are an opportunity for you guys? Sure. Well, I'll touch upon it, and then Geoff can talk about some of his market research and conversations with the KOLs. So the number one reason why Dupixent is discontinued, and within two years, over 50% of patients go off of Dupixent, there's needle fatigue, but there's also injection site pain. And that is where we see the discontinuation rate, not from conjunctivitis. And just as a reminder for our Part A trial, we did not see any ISRs in our Part A data to date. Not that we'll never see that, but to date, we haven't seen it. Yeah, and maybe I'll add, Geoff, the biggest opportunity in the AD biologic space is really biologic penetration. We are at about 10% right now, much less so than other INI diseases, plaque psoriasis, RA, IBD, 10%. So it's a huge opportunity for us. Right now, when you look at patients that are on topicals, they're less likely to move over to a biologic that they need to take nine dosing days in induction, and then they're injecting every two weeks. So 26 a year versus the ability to move into maintenance with an every two to four times a year 777. So we fully expect an opportunity with physicians and with patients is to drive much deeper into that biologic penetration with 777. Okay, yeah. That's helpful. And maybe from a, I know we're going to talk about the Part B of the study. What opportunities do you see for differentiation there? Maybe what does kind of a win look like from a clinical perspective? We can talk about the commercial implications of that. I'll start, and then I'll have Geoff add. So first of all, on Part A, we see a win with the dosing that we could provide patients of every three- and six-month dosing. We are the first company to test maintenance dosing in Part B, and it will inform our Phase III dosing, where in any scenario, we're going to be testing every three- and six-month dosing in maintenance. So there's a win there. For Part B, our goal is to replicate the strong data that we saw in Part A, where we saw very strong EASI-75 results, whether it was absolute or placebo-adjusted, including similar efficacy on IGA 0/1 and EASI-90 to DUPI and Lebbery. What we are doing in Part B is testing the dose-response curve. So we are testing a lower dose so that we can go to the agency with a lowest efficacious dose. But importantly, we also want to see whether we're leaving any efficacy on the table. So we are also testing a higher dose in our Part B, and that higher dose is twice the exposure of Ebglyss. Yeah, and commercially speaking, Geoff, I think when you look at the product profile that we presented coming out of 2A, it is clearly the most preferred product profile of any biologic in AD by both physicians and patients. So if in Part B we're able to replicate that product profile, we see that as a huge win. Anything above and beyond that, it doesn't change the way we go to market. It doesn't change our marketing strategy. We already have the most preferred product with the Part A data. So it could impact things like gross to nets positively for us if there is any additional efficacy that's left on the table, but we certainly do not need that to win. Yeah. Dosing alone wins. What are the challenges, though, in moving from every three months to six months? From a mechanism or from a tolerability perspective, do you add extra risk if you have higher dose? I just wasn't sure what maybe the nuances between every three months is very differentiating in its own right, but six months is like a real gold star. That's an amazingly commercially relevant product. Obviously, you want to aspire for that, but I wasn't sure of the extra challenges to get to that infrequent of a dose. We have confidence based on what we see from a PK modeling point of view for every six months. So just as a reminder, our every three-month dosing is exposure that is slightly higher than what is seen with Ebglyss, and our every six month is slightly lower. So all we would need to do if we saw in our Part A maintenance a lower efficacy on the six months is to increase the dose in our Phase III trial. If we saw the efficacy that we're looking for, then we can decrease the dose of every three months. So again, in any scenario, we are going to test both and launch with both. It's just going to be optimizing that dosing going into the Phase III. Okay. But you don't engage, for example, the immune system or have other. It's all in your mind, like just PK, PD, and pharmacodynamic kind of issues. That's what we've seen generally with this class and also with our own data so far. Yep. Okay. Yeah, along those lines, any PK/PD metrics that you will show in the maintenance, the Part A maintenance data that gives more confidence in the 777's profile versus DUPI? The answer that we're looking for that matters and is well laid out from Dupixent, the market leader, is showing maintenance of response at 52 weeks. So for those patients that achieved EASI-75 or IGA 0/1 response, what is the percentage that is maintained at 52 weeks? And for Dupixent, for EASI-75, that's just over 70%. For IGA 0/1, it's just over 50%. So that is what we'll be looking for to then determine how to optimize that Phase III dosing strategy. Recently, you also presented data at EADV about the rapid relief profile of 777. Just give us some color on how important that property is for the drug and how that competes with the other kind of drug in the market. Yeah. So thanks for the question. We are thrilled with the data that we presented at EADV on statistical significance for itch at 48 hours. And I'll tell you, it is really important to the product profile. So when you ask physicians what's most important for them, they'll tell you EZ-75 scores when they're trying to decide what product to use for their patients. When you ask patients what's most important, the rapid itch relief kind of floats to the top. And I think you can see this in the launch of Nemluvio, right? Really strong launch, subpar in terms of lesion control, but really good on itch. So it shows the value of that itch. For us to come forward with a product that has statistical significance on itch at 48 hours, as good or better lesion control with EASI-75 than Dupixent or Ebglyss and the dosing of Skyrizi, it's really the trifecta. It's the perfect product in the biologic space for AD patients. And we're really diving into what's taking place with the sensory neurons. And if you look at the IL-31, it's clear in the Nemluvio data that IL-31 does, in fact, impact those sensory neurons. For us, we've seen a lot of great work come out of Brian Kim's lab out in Mount Sinai, which now we know that IL-13 at the right dose, at these higher exposures, does, in fact, have impact on those sensory neurons. And we believe that is why we're able to show that 48-hour relief. I'm just going to say, is there? I there? I know from the Part A, there wasn't. It's hard to look into some of the smaller numbers, but is there any like a Dupixent experienced patient, someone who's either failed or non-responder, or is that a more difficult patient for you guys, and is that a meaningful part of the market? I'm just looking to a larger Phase III and what you could kind of focus on. Yeah, so Geoff will address the market. To clarify, in Part A, we had all biologic naive. In Part B, we are testing up to 20% biologic experienced. So we will see the answer from that data that we expect in Q2 on Part B induction. From a market point of view, it's interesting in terms of new patients versus existing. Yeah, so that's part of the reason why we will, in fact, have up to 20% biologic experienced in our 2B. It is an important part of this market. And the reason is because when you look at Dupixent, only one out of two patients actually reach an EASI-75, right? And that's a critical endpoint for physicians because it really moves patients from moderate disease to mild disease whenever you move to EASI-75. So we believe that there are really two major areas that we will build share with APG-777. The first is simple, and that is, in fact, switches. So you're going to have patients that want more efficacy, or you're going to have patients that just either have ISRs or they don't want to take injections every two weeks. Those patients will look to move. In fact, we have some really strong market research with patients, even controlled patients, who would prefer to switch at a very high rate, close to 90%, if they have similar efficacy and safety, but in every three-month dose. So it shows the value of that dosing proposition. And then secondarily, we will build share, not just with switches, but with biologic naive patients. So again, only a 10% biologic penetration in the AD space, meaning that we have loads of patients that are on topicals that haven't made that transition yet, that are much more likely to make that transition to a quarterly dosed option. In fact, market research shows that they are three times more likely to move toward 777 quarterly dosed option than Dupixent every two-week injections. Patients want to take the drug and then not think about their disease. And that's what every three and six months will provide in addition to all these other features. I know you guys haven't you talked about Phase III at a high level, but is that kind of the thought that 20% would be biologic experienced also in the Phase III, or you haven't quite? We haven't quite finalized what that's going to look like, but yes, we would expect to have biologic experienced. It's a pretty straightforward path laid out by the FDA. We will need to replicate Phase III trials versus placebo. Companies often will then do a third trial with TCS to make sure that it's part of the label. And then on Part B, you have also mentioned that you are going to test higher doses, higher exposure levels, right? Maybe talk about the efficacy or other profile that you could see with higher dose levels and whether there is a ceiling that you could reach within terms of efficacy. Yeah, maybe I'll start with this one. I think it's the right experiment to conduct, right, is to increase exposures just as we're doing in Part B. We already had higher exposures than Ebglyss in Part A. We're going to increase those exposures, or we have increased those exposures in Part B. And the data, it's the right experiment to do. The data will come back. I'll reiterate a point made earlier. We do not need higher efficacy to win in this market and become the most preferred product. So anything that comes back to us from Part B, higher exposures, is complete and true upside for the product. Remember, of course, we do need to test that lower range of efficacy dose for our conversations with the FDA, which we expect to have before the end of 2026 so that we're prepared to start our Phase IIIs by the end of 2026. Let's stick with 777, but asthma and beyond. So maybe give us some context for biologic penetration there, and then maybe in the Phase 1b, which is, I guess, early part of next year, how are you guys thinking about that, how that could play out from a headline perspective? Absolutely. So Phase 1b asthma in Q1, we selected it as our first expansion indication because there was an approximate 30% overlap between AD and asthma patients. And for Dupixent, it's the second revenue driver after atopic dermatitis. For our data in Q1, we're looking at a FeNO readout where we're looking to have a similar reduction in FeNO in terms of parts per billion of 15-20. Ebglyss was lower in the 10-15 range. And so for us, a win is to have that 15-20. We look at FeNO as an endpoint because it's a good surrogate marker for what we would look at in later trials, which is exacerbation. Then our plan is to take this data from the 1b trial along with the dosing data we get from our Phase II Part B and then start a Phase II trial in asthma later in the year. Gotcha. And the biologic penetration as a comp, I know Ebglyss just launched more or less, but is there a DUPI ceiling, I guess, on the utilization? For asthma? Yeah. Yeah, no, again, these are relatively new compared to, think about, the more mature INI markets like an RA or an IBD that's closer to 60% penetration. So there is an incredible amount of runway available for asthma. And it is a large market. It's not the size of AD, but it is a large and growing market. And we expect, to Jane's point, our first expansion to go there for a number of reasons. We think that we're already going to be in the allergist offices anyways. So it's a nice secondary indication for us. And it is growing. Now, AD is growing at about 25% a year right now, year to date. And again, a little bit lower biologic penetration, but the reality is both of these indications, we're scratching the surface on. Lots of runway from a biologic penetration, and they continue to grow year in and year out. As we look at the monotherapy, there is for asthma patients that we've seen in Dupixent, it's a type 2 driver, right? So we will be looking at a subset of the patient population that is EOS greater than 150, which would be consistent. So how do we then break through an efficacy ceiling? It's then through a combination. Similar story that we had for atopic dermatitis. For respiratory, we're looking to combine IL-13 with our TSLP antibody to see if we can get a higher efficacy potentially across a broader patient population. So you wouldn't do monotherapy. You would do the doublet, you think, if you look to, say, COPD, or you think that would be a better approach outside of AD? We will take forward a mono, and then we will follow up with a combo approach, so very similar. We want to be a serial innovator, particularly in AD, so we will launch with monotherapy and follow with the combo 279, and then the same in the respiratory. We will launch with a mono for asthma and then look to follow up with a combination. Okay, makes sense. For staying on asthma, have you had any so far, like kind of success? I know the endpoint is like FeNO reduction. What kind of percent would be a reduction that you're seeing to be comparable? We have a clear bar. Anything below 15 would be a failure for us. And so we're looking for 15 and above, similar to DUPI in terms of parts per billion reduction. Let's say it's around like 13, 14, 15, and would you still use that as a combo therapy? Or would you not proceed with the program? For the combo, there's a few different things that we want to see. Right now, lunsekimig, which is their IL-13 TSLP antibody, will have data in 2026, including asthma in the first half. That data will help inform how we are going to take forward a combo in addition our Phase 1b mono data. I know for Dupixent, COPD is the newer indication versus asthma. There are some similarities and some differences on pathophysiology. How are you thinking about COPD in addition to asthma and then beyond, looking to say IBD indications, etc.? So as you point out, there's different drivers of disease, right? COPD could have more diverse drivers of disease. What we like with the combo is you're addressing both central drivers as well as local drivers of disease. So we think that could be important, whether it's asthma or whether it's COPD. Anything to add from the market point of view? I mean, certainly the unmet need in COPD, right? That is meaningful to what we see as to why we would take that forward in there in addition to asthma. It's just opportunity, right? Each one of these markets are underpenetrated when it comes to the biologics. COPD, you're really dealing more with pulmonologists versus asthma, could be pulmonologists, but high level in the allergist office that's also dealing with AD. So it really allows us, with our first expansion, to unlock the entire opportunity within AD while also increasing our footing with asthma, and then in time, just as we saw Sanofi and Regeneron do, you can look to move into COPD and other disease states. Yeah, makes sense. And then maybe you can kind of pivot to combo strategy that you are going to use. So next year, you're going to read out the APG-777, which is the combo with DUPI, and you're running head-to-head trial against DUPI. So maybe talk to us about the confidence you have in the combo, and then you have kind of a bold move to compare against DUPI, then your expectations in terms of efficacy, what you plan to see there. So we chose the combination of 777 and 990, which is our 279 co-formulation because of the orthogonal mechanisms, right? IL-13 has that deep type 2 inhibition that you see across all AD patients. Where you see heterogeneity is where the type 1 and the type 3 inflammation contributes. And OX40 ligand, as we've seen with Sanofi's amlitelimab, has that breadth of type 1, 2, and 3 inhibition, but not the depth on type 2. So by combining the two, we hope to see a greater efficacy than we see with Dupixent. So what kind of greater efficacy? We're looking for eight to 10 points greater efficacy on any of the endpoints, whether it's EASI-75, so we're bringing more patients up to that level, or the deeper endpoints, IGA 0/1 and EASI-90. So that trial, as you noted, reads out in the second half of 2026. It is designed to provide a signal with a total of 50 patients. And then from there, we'll determine a Phase II trial and the number of patients that we would need for a Phase II. But the goal is to get an efficacy that is more similar to JAKs, but without the safety concerns, which derms don't want to deal with, like with JAKs and the concerns that come with that class of drugs. In our preclinical trials of this combination, we did not see any signal on the safety side. So we'll have to prove that out in Phase 1b head-to-head. I know for keeping on the combo conversation regarding your 333 and 273 combo in the asthma, and you mentioned you're waiting for the comparative readout in first half. What specific efficacy or safety signals you are looking at from the readout that will inform you on your own development of the program? That's certainly the exacerbation rates, right? And are those greater than what is being seen with Tezspire and others? So that's what we're going to look at and use that information combined with our own data to date. As you look to the combo, the 279 combo, are there inflammation biomarkers that maybe could predict where you could go next from an atopic dermatitis here and asthma, COPD, or IBD here that you could maybe fine-tune the indications that you could go after? Or are you just looking at it like, let's get the first set of the data and then we'll kind of move from there? We're pretty focused for APG-777 on atopic dermatitis, right? And so I think the data and the additional biomarkers, etc., will inform us what if, but the priority is to determine the next steps to bring that as our second franchise, our serial innovation in AD for atopic dermatitis, right? So that is the foundation of the company. We want to be a serial innovator in atopic dermatitis like you've seen with the success of a Vertex or a Gilead, constantly improve upon ourselves in addition to the pipeline and a product potential that we see with APG-777 as a franchise. Okay. That makes sense. It's funny because a lot of the more mature legacy franchises have been to things like HS and the nasal polyps, like all the many other indications, but it definitely is well after they established atopic derm or respiratory as the foundational kind of thing. So maybe they didn't have as many growth opportunities there, but you have to be in it in the core indication first, obviously. We have a path that's very well established, right? What Dupixent has done is determine the efficacious dose in Phase II for a therapeutic category and then for additional expansions within derm, within respiratory, within EOE. They go straight to a Phase III. That's very well established in terms of the pipeline and a product opportunity. Each of these indications can be, and many are already blockbuster status for Dupixent, right? The difference is if you look at their overall revenue, the majority comes from AD and the biggest opportunity. It's not just the largest market. It's the fastest growing market and the least penetrated. We think that by 2040, this could be a $50 billion biologic market. So does it make sense to expand? Absolutely. But to your point, Geoff, I think it makes good sense to start with your largest opportunity, and we see significant differentiation in that space. Then looking at a bigger picture in terms of commercial and landscape, your drug could launch in 2029 or around that time frame. Given the strong performance of Ebglyss and Nemluvio commercial launch, how do you think the kind of market segment could look like by that time when 777 potentially launches? Yeah, yeah. Thanks for the question. I think first I would say we are really encouraged by the recent launches. Nemluvio is annualizing at about $500 million a year right now. Ebglyss is annualizing at about $650 million a year, both right in their first year of launch. And what's really interesting, going back to the point of the size of this market, is they're doing that well without much differentiation, and they're doing that well as Dupixent continues to grow and have its best quarters. So the market as a whole is growing at 25%. The new-to-brand prescriptions are growing at 49% right now in this space. So we expect that the market continues to grow, continues to move patients from topicals over. We believe that both physicians and patients have a high expectation around dosing options in this space, just as they've been given in other IL-13 indications like plaque psoriasis. So we think that if you look at our market research, if you look at this product profile, when you can bring forward a product that impacts EASI-75, we've had the highest, as a reminder, we had the highest in Phase IIa, highest absolute and placebo-adjusted EASI-75 scores of any biologic. We now have this rapid itch relief that you get with Nemluvio in that first 48 hours, and we're bringing forward what both physicians and patients want, quarterly and semi-annual dosing. So we expect that the market evolves, but we also expect that we are a first-line agent and we are the most preferred product by physicians and patients. In terms of securing kind of payer access, I mean, these drugs were able to get good access at the onset of launch. How do you see 777 kind of being able to get favorable access, considering there will be other drugs in the market at that time as well? Yeah, I've had a number of questions on access in the last year, and I continuously say that the AD market, it needs new options. And what I mean by that is right now, so you think about Dupixent, only one out of every two patients is going to reach an EASI-75. 50% of patients discontinue within the first two years. Patients will be moving. This is not a winner-take-all market. It's not a one-and-done, similar to plaque psoriasis. There are eight products in plaque psoriasis that do north of $2 billion a year. I mean, the clear winner is the quarterly dose Skyrizi, right? But eight products doing that. Why is that? It's because patients need options. If something's not working or you have a side effect or whatever the case may be, you need to move to something else. If you're a payer, and this is why I said before, and you can see the reality, both Ebglyss and Nemluvio have really strong commercial access, 80% and 90% commercial access. Because as patients move from one product to the next, if it is not covered by a payer, then that payer is paying full list price. When you have that many patients that aren't getting what they need today, even whenever we come to market, two out of every three patients are reaching EASI-75, there's still going to be a portion of those patients that may need something more. So we have the highest confidence level that we will get first-line access. Payers pay for products that will be used. There's not a product in the AD biologic space more preferred by physicians and patients. In fact, we had a market research done recently looking at our Part A profile versus all of the other products in the market and just simply asked physicians to force rank what product they would use first through fifth, what's their number one biologic. 60% of physicians said, "With your 2A product profile, this is our number one product." So it will be used. If it's going to be used, it needs to have contracted access in that first-line space. I guess just the last question to follow on the chances when you think about the overall sort of commercial strategy, is there something that you can do in Phase III to maybe help you with the maybe a nuance with either differentiation with payers or physicians that can maybe give you a bit of a leg up as you think about formulary discussions and PBM negotiation? Yeah, I think, yeah, there's quite a bit that we're learning from conversations with payers, market research, and one-on-one conversations. And one of the reasons that we've created our commercial team here at Apogee so early is to ensure that we have that dialogue, that open dialogue with payers. We're looking at ensuring that our Phase III program includes what's important, not just for the disease state physicians and patients, but also payers for access. And there are a number of things that we are including. But I'll tell you, for example, the quarterly and semi-annual dose to really push both that early gives us that advantage. To bring forward an auto injector and a prefilled syringe at launch gives us that advantage. Most have not done that, frankly. So there's a number of things that we're learning to ensure that the most amount of patients early on can be prescribed, get the product. It pings the payer. They see the value early, and the more they see that, the more that they know that they need to have access for patients. Awesome. Jane, Geoff, thank you so much. Great conversation. Yes. Thanks so much. Appreciate it.