I'll sign up for it. Okay, thanks everybody, and good afternoon to day two of the Second Annual Guggenheim Healthcare Innovations Conference. I'm Seamus Fernandez, one of the Biopharma team's senior analysts here, and I'm joined by Apogee Therapeutics. We have most of the members of the executive team here. Michael Henderson immediately to my right, CEO, Carl Dambkowski, Chief Medical Officer immediately to Michael's right, and Jeff Hartness, Chief Commercial Officer to Carl's right. Really very excited to have you guys here today. As one investor pointed out to me today, now appropriately living up to my best idea, Moniker. Thankfully, investors caught up to where we're particularly enthusiastic. Great to see that. We've been through sort of the exercise before, but I think if we just kind of think through assets and execution, Michael, if you wouldn't mind, just reiterate the core of Apogee's strategy, the differentiation opportunity, and why you're not just exclusively a long-acting antibody story. Yeah, no, thank you for the opportunity. For anybody that wants to hear our story better articulated, please read Seamus's notes, but I'll do my best. We are developing best-in-class antibodies going after the most exciting, biggest markets, and I. Our lead program had data over the summer. It is a fully optimized IL-13 antibody for atopic dermatitis. We had really exciting data showing rapid itch relief, great lesion data, and the potential for improved dosing. Across all the markets that we're going after, we want to improve dosing and push on efficacy as well, either via our monotherapies in the case of atopic derm or our combination approaches. We have combinations which can be co-formulated. We design them from the beginning to be able to do that so that we can kind of be serial innovators in this space. Atopic derm is our lead. The full pipeline and the product potential DUPIXENT has, we want to be able to follow. Three to six-month dosing, optimized efficacy, and single 2 mL injections are what we strive for in atopic derm, then asthma, EOE, COPD, the full range of indications. Now with kind of how the field has played out, when we show our data to docs and look at the market, we believe that we have the most exciting frontline drug in development and are the next drug to launch in a meaningful way later this decade. Jeff will get in that kind of all the commercial build that we're doing there as well, but very exciting space and ahead of a very rich catalyst rich 2026. We're spending a lot of time just on all the data that we hope to deliver next year. Great. There's always been kind of an extensive dialogue around assets that could do similar things, a push from China. Just talk to us a little bit more about your capabilities and what you would view as both kind of a competitive and/or comparative advantage. Yeah. In the very beginning, when we first came out of stealth mode right ahead of the IPO, right ahead of entering the clinic a few years ago, the biggest question that we got was, why is nobody else doing this? At that point, we had been working on it for a number of years to create the best antibodies. Since that time, we've just continued to build upon and accelerate the lead that we have. That is, I think, just a key advantage we have. Other people are now talking about it. They're talking about entering the clinic. They're kind of knocking on the door. We're at the point where we plan to kick off our phase IIIs next year. We plan to be approved this decade well ahead of biosimilar entry into the clinic, bringing our combos to the market when other people are bringing their monos. We are always aiming to stay a step ahead. We have been fortunate along the way to have really nice investor support. We have roughly $1 billion raised to date, over $900 million of that still on the balance sheet, which gives us the funding to take these big shots, which otherwise for an upstart is quite hard. By virtue of being first, we had that advantage. We have been able to capitalize on it. We can continue to accelerate the lead that we have and then build out the moat via IP, but also just via our combination approaches and kind of broadening the lead that we have in each indication. Just from a commercial perspective, we've talked about this a lot, and this is maybe a little bit more of a question for Jeff, but we've seen a huge number of markets emerge, whether it be originally RA, but more so psoriasis, the opportunity to further penetrate AD. Where do we stand in that cycle? How have other AD launches gone? Where do you sort of see at least 777 monotherapy fitting into that opportunity? Yeah, thanks for the question, Seamus. I think first of all, I'll start with the latest launches. We're highly encouraged with both EBGLYSS and NEMLUVIO launches. NEMLUVIO right now is already annualizing at about $500 million a year. EBGLYSS is right now annualizing at about $650 million a year in their first year of launch. That is encouraging given the fact that they have limited differentiation versus the market leader. I think also encouraging is the market itself. If you look at the IQVIA data, the AD biologic market is growing right now north of 25% a year. That is year over year. If you look at the new-to-brand prescriptions, they are growing 49% year-over- year. That is really sort of a leading indicator as to where the market is going. We are excited about it being the largest market. To your other question about penetration, you're talking about this market only having biologic penetration of about 10%, meaning 90% of these moderate to severe AD patients are staying on topicals. When you compare that to plaque psoriasis, that's between 25%-30%. If you compare it to IBD biologics, that penetration is about 60%, meaning we have a very long runway ahead of us for market growth. We're coming into this space as the most preferred product by both physicians and patients. Great. It doesn't seem like a lot of headwinds there, but how do you react when asked about the payer environment? Obviously, other launches are doing well. It seems like payers are seeking competition. From your perspective, when or as the opportunity emerges to launch, how do you envision the payer environment sitting in that timeframe? 2029, if you're going to kind of bring out your crystal ball. Sure. I think we'll start with these last couple of launches and where they are. As expected, payers are quickly giving access, first-line access, biologic access to both NEMLUVIO and EBGLYSS. NEMLUVIO has about 80% coverage in the commercial space. EBGLYSS has about 90%. This is expected because when you look at DUPIXENT, about 50% of the time patients reach EASI 75. Within the first two years, about half of the patients discontinue, meaning that they're going to move to another product. As a payer, you really do need optionality in the market. You can't have a single product, very similar to plaque psoriasis, where we have eight products that are doing north of $2 billion each, all of which have strong coverage. I expect that will continue. I expect that when you have a product that is this much preferred by physicians and patients, what's going to happen is physicians will write it, patients will want it. That volume of prescriptions is what really drives a payer to give access. We fully expect that we will be driving that volume. We fully expect in this decade that we will have first-line biologic access. Great. Maybe we can talk a little bit about the 777 phase II data, lead asset. You guys really provided what I would characterize as a definitive phase II study to prove the activity of the product. Maybe just talk to us about the data and then how you would expect that to kind of translate into your phase III and what do you need to learn between here and now to be able to start that phase III study? Yeah, Carl, do you want to speak to that point? Yeah. So happy to. Last summer, we put out phase IIa data, APG 777 versus placebo in moderate to severe atopic dermatitis. I think kind of how we kind of look at it and really how it has been described to us by KOLs and physicians is lesion changes as good, if not better than DUPIXENT, itch changes as rapidly as NEMO, and the dosing advantage of SKYRIZI. They see that as kind of a winning profile overall. For us, success as we move forward in terms of induction data is really replicating what we saw in part A, two-thirds of patients responding in terms of EASI 75 compared to just 50% with DUPIXENT and LEBRI. That is what physicians look to, EASI 75 specifically as the key marker of success for their patients when they come to clinic. That's really the key thing that we're looking for in part B. Between now and then, we'll also have maintenance data, base cases every three-month dosing there where we have similar exposures to lebrikizumab, but we're also testing every six-month dosing too. Excited for that potential kind of upside there as well. Those two components, part B induction data and part A maintenance data, really come together to be able to design the right regimen for phase IIIs. The data I just talked about was from a regimen that is now the mid-dose in the part B induction. We are testing on higher dose. Our goal there is not that physicians tell us it is needed. It's that we didn't want to leave any efficacy on the table. Whether it replicates or is better, we want to walk away knowing we fully explored that dose response curve there. Perfect. I guess we had some interesting attempts at intervention, maybe actually mildly successful on NEMLUVIO in terms of claims around itch. Maybe you can just help us understand how effective is 777 on itch and what have you learned from your own phase IIs? Yeah, right. When we look at one of NEMLUVIO's biggest claims, it is itch relief within 48 hours. JAKs also make a similar claim, although they've done it quite differently too, which has led to different FDA responses. We are looking at that too because what patients and physicians want is they want some early relief, some early sign that they know they're getting better too. It is not that complete itch relief within that time period, but some. What we've seen is within 48 hours, we see about a 15% decrease in itch within 48 hours. DUPIXENT has shown something like 6% or 7% change in the first 48 hours. NEMLUVIO with TCS, so NEMLUVIO with topical corticosteroids, has shown like 17% or 18%. We are very similar to NEMLUVIO, with theirs being with topical corticosteroids, ours being without. The reason we think that's happening is we know there's IL-13 receptor alpha-1 on the sensory neurons. As we're giving these higher exposures, we think that it's actually impacting sensory neuron level. That's how you can get the 48-hour itch relief instead of the one to two itch relief, which might be just because you're starting to change lesions overall too. Got it. Maybe as we kind of advance through to some of the other programs and opportunities, just your level of conviction that we have an every three-month treatment here with 777 at a minimum and what you see as the opportunity to potentially bring forward even a six-month regimen. When would we maybe prove that out? Yeah. Our belief is that we will have both at launch. The reason is everyone runs maintenance as part of phase III. We're the first company, to our knowledge, disclaimers, that is actually getting data prior to starting phase III in maintenance by virtue of our part A and part B nested design. We do not view it as what we have in every three and six-month dose. It is we will take both in the phase III as our intent. We will learn from this data what dose we need to take to ensure odds of success. The every three-month single injection, we're always at or above EBGLYSS's Q4 week regimen, which had very promising maintenance data. We have very high conviction there. Our every six-month dose, it's also a single injection. If that delivers, great. We can give a lower volume every three months and a similar volume that hits every six. Or worst case, we give two injections every six and one injection every three. Our intent is to have both. We think that docs want to see both. Some docs do not want to just have Q6. They want to have a Q3 and a Q6. We will learn what exposures maintain efficacy in Q1 of 2026, which will inform the dosing we take into maintenance in the phase IIIs, which will start in the second half of 2026. Okay. We also saw some, I guess, preliminary results, not the official results, from exploration of EBGLYSS. Can you guys maybe just talk about your understanding of those studies and how competitive those data would be with your own programs? Yeah. Lilly recently PR'd some data where for patients that had been stable on EBGLYSS and maintained response for 100 weeks, so for two years at every four-week dosing, if they then went to every eight-week dosing, what happened? The majority maintained response. They did see a drop compared to what patients were on with Q4 weeks, suggesting that they're kind of on that threshold. I think it's interesting data. When we've talked to docs about it, I think great for patients that are still on this drug after two years. In the label at some point, maybe we'll have the ability to put them on every eight weeks. Their feedback was it's a small number of patients as part of that study. There is survivor bias inherent in patients that have been well controlled for two years, just like some patients that have been well controlled on DUPI for two years can go to Q4 week DUPI. We know from DUPI's phase III that Q4 week DUPI loses a lot of efficacy for patients out the gate. What we like is that data, our Q6 month single injection that we're currently testing, the C trough of that at its lowest point is 50% higher than what EBGLYSS Q8 weeks reaches. To the extent that data is real across a wide patient population, we should be sitting well for our Q6 month data that's coming in Q1. To the extent that we need more, we'll learn that and be able to react. Great. Carl, maybe because Michael brought up exposures, this is a good time to talk about asthma a little bit. What do we know about asthma in terms of IL-13's activity there? A lot of folks that we talk to just sort of perceive it as a failed effort. I think we look at it a little bit differently on our team, and I know your team does as well. Maybe you can just give us a quick walk through there and what you would hope to show in the first half of next year. Yeah. Yeah, of course. Right. For those of you guys who don't know, LEBRI has a mixed history in terms of asthma. For us, in some ways, this is good for us because we've learned a lot in the last 15 years since their readouts and can really adapt to that. There are really two reasons we see that they probably failed those trials. One is dose selection. Even the highest dose they tested there, 125 Q4 weeks, is like greater than 4X their approved AD dose too. Way under what their AD dose was. The second is patient selection. They went for sometimes the normal thing, which is they got overly seduced by a really large but ill-defined patient population and went for all comers. Anybody that has asthma, regardless of their history in terms of moderate to severe asthma too. No eosinophil cutoff, no history of exacerbations. Post-hoc analyses have both shown that had they enriched their population for either EOs 150 or greater or history of exacerbations, one in the past year or greater, those studies would have been successful too. We can learn a lot from that as well. When we look at our first quarter asthma readout next year, we're looking at approximately 20 patients, three to one randomized to APG 777 versus placebo, primarily for a FeNO readout. FeNO is a fraction of exhaled nitric oxide, a really good biomarker in terms of asthma and has a pretty good correlation with annualized exacerbation rate, which is the provable endpoint. What we'll look for there, one is kind of a comparative point, which is compared to DUPI and LEBRI, do we see a magnitude of change that is more similar to DUPI than to LEBRI? DUPI has shown kind of 15-20 parts per billion change in terms of their FeNO reduction. LEBRI showed more like 10 or 11. We think that's probably largely due to dosing because this is at their 37.5 mg and the 125 mg doses. Probably somewhat related to dosing there. At least that's our view. First is the magnitude. Obviously, as Michael mentioned, we're always looking at making sure we're getting to at least every three-month dosing, if not less frequently. We'll look for a durability of that response out to at least three months. Great. We have to talk about 333 because you just put out a press release on that. Remind us again what you showed in the press release and how you're planning to approach the sort of TSLP mechanism, particularly in the context of quite a crowded mechanism, at least. It feels like a crowded landscape, but it's really not that crowded yet. TSLP is a very popular monotherapy. We're not trying to compete as a monotherapy. Our approach with TSLP and with OX40L for that matter be a combination with our IL-13. When we looked at our pipeline, we wanted to create antibodies that could be co-formulated. We engineered them from the beginning to be co-formulated. Our goal is to reach quarterly or better dosing as a co-formulation. We achieved that with our DERM program, which is now running head-to-head versus DUPIXENT. Data coming second half of next year. In respiratory, IL-13 and TSLP, there's really promising proof of mechanism with Sanofi's lunsekimig, which has a 9-11 day half-life. We showed with our data yesterday that our TSLP as a monotherapy is showing suppression at the lowest dose, which is a fraction of what you would need in a 2 mL out to six months, nice prolonged PD suppression, which unlocks our ability to get to a quarterly or better dosed combination approach. It was kind of the last piece of the platform puzzle to be able to have this combination in DERM and combination in respiratory to take forward. We are really glad with the results. Obviously, TSLP is safe. We saw similar benign safety in that and just a very well-behaved antibody. Now as lunsekimig starts to read out and others look at kind of where TSLP can play, we will be able to react to that data and come with a better dosed solution where we can also titrate dose. Push IL-13 and have an appropriate amount of TSLP inhibition. Maybe we can talk a little bit about just sort of the choice of others are pursuing bispecifics. We've already heard about another sort of private company that pushed forward or tried to push forward a bispecific and actually came up against ADA. In that context, maybe you can help us understand your own approach with combinations. Yeah. From the very beginning, we years ago thought, should we do bispecifics, which have a more straightforward regulatory path, or should we do combination co-formulations, so fixed dose combos? Our view is there's an exposure response with IL-13. There's not with OX40L. So bispecific doesn't make sense. Same with IL-13 and TSLP. TSLP, very flat dose response. You don't want the one-to-one inhibition. If you don't have that and there's no synergy from the bispecific, then there's just a list of problems. You get a shorter half-life with shorter dosing. Sanofi's 9-11 days. Other even YTE half-life extended bispecifics are kind of getting into the two weeks, three weeks if they give a lot and get above kind of the TMDD degradation range, which just means multiple injections. When we looked at kind of these markets, the realization we came to is there's no free lunch. You have to run an active comparator if you don't want to be the six-line agent. If you're two mechanisms, it's really easy for a payer to make you be the later mechanism that needs to step through everything else in the absence of head-to-head data. Kind of accepting that reality that if you want to charge more and have frontline versus a monotherapy, you need to show proof, then great, we'll run the active comparator study. All of a sudden, the regulatory point is kind of null and void. If you've got to run the active comparator anyways, you might as well set yourselves up to be able to titrate the dose, get to the optimal half-life, the optimal just commercial presentation. That's been our approach kind of through. Bispecifics have had a history of ADAs. It seems like that has not been totally solved by the field yet. Someone at some point might solve it. I think it's just going to be there's going to be a place for them as later line agents where you're willing to sacrifice dosing for a niche of a patient population that doesn't respond, in our view, to our frontline mono or our co-formed combo, which will still be quarterly or better dosing and provide that extra bit of mechanism for patients that need it. Maybe just as a final question, your combo data with OX40L, help us understand where the opportunity sits for that. Again, a bold move. You're not exclusive in the bold move, but going head-to-head versus DUPIXENT, what you're hoping to see in those data. Yeah. I mean, I think that I'll start with what are we looking for in that data. I think what we hear repeatedly from physicians or payers on Jeff's side of things is we need 8-10 percentage points on an endpoint to show that we're really separating from monotherapies. We want to prove that out early on so that it's not kind of just like keep hoping that the next study looks good too. It is really important for us that we're looking at it. I think depending on how that data comes out, we're looking at it in biologic naive patients, so frontline patients. I think that if we are seeing better efficacy there, we can have a place for that in frontline. Great. Unfortunately, we're out of time. You guys have plenty to talk about as usual, but really excited to see what is going to be a very busy 2026 in terms of all the catalysts. Thank you for having us. Thanks, guys. Thanks for coming.