Good morning, everyone. Thanks for joining us here at the Leerink Partners Global Healthcare Conference. My name is Tom Smith. I'm one of the senior biotech analysts here at Leerink. It's my pleasure to welcome our next company to the stage, Apogee Therapeutics. Happy to be joined up here by CFO, Jane Pritchett Henderson, CMO, Carl Dambkowski, and Chief Commercial Officer, Jeff Hartness. Thank you all for joining us. Jane, why don't you go ahead and kick us off here with a brief overview of Apogee for those in the audience who may be a little bit less familiar with the story. Perfect. Thank you. Thank you for having us here. Apogee is focused on the largest I&I markets that are also the least penetrated. Our goal is to transform the standard of care by developing biologics that could be best in class in terms of both dosing as well as efficacy. Our lead program, APG777, is targeting IL-13, a known target, known biology, known mechanism, but with an optimized antibody across half-life, formulation, and manufacturing. We are testing and prioritizing triple seven in atopic dermatitis, the largest I&I indication. It is currently in phase two trials. The first part of the trial is a 16-week induction where we are testing higher exposures that could lead potentially to higher efficacy. Following that 16-week induction, we are testing every three and six-month dosing in the maintenance setting. That 16-week data for the induction will read out this summer in important phase two part A data for us. When you think about two of the potential leader and the potential leader in the space, Dupixent and Ebglyss in the maintenance setting, they are dosed every two to four weeks. Potentially transformational for patients. For triple seven, beyond AD, we have a pipeline and a product potential. Our first expansion indication is asthma. That's important because there's a 30% overlap between AD and asthma patients. The second expansion indication is EOE, and we will initiate phase two trials this year and next for triple seven in asthma and EOE. We see the future of I&I in combinations. Our first combination that we are testing is the combination of our IL-13 targeting antibody triple seven with our OX40 ligand targeting antibody, which is 990. That combination, which will be in a co-formulation, we call APG279. We see the opportunity of very deep type two inhibition with triple seven combined with a broad type one, two, three inhibition of OX40 ligand is potentially providing not only better efficacy, but also, again, better dosing for patients. We've decided to run a head-to-head of 279 against Dupixent. That trial will start in a phase one this year and will read out in the second half of 2026. Multiple opportunities to not only transform dosing for patients, but also to shoot for better efficacy. In combinations, we're also looking at potential for respiratory in asthma and COPD, and we'll be combining our triple seven with our TSLP antibody that's in a phase one currently called triple three. We're in a really strong cash position. We announced our year-end balance sheet of over $730 million. That takes us with a cash runway into Q1 of 2028. We are prioritizing that capital to advancing triple seven as a monotherapy in AD to potentially launch this decade. That's great. Awesome. Thanks so much, Jane. Yeah, let's start with 777, your anti-IL-13. You mentioned the proof of concept induction readout in the middle of the year. We call this out as one of the most important potentially disruptive catalysts in the AD space this year. Maybe you could just start by reminding us some of the modifications you made to 777 using sort of a Libri concept backbone and how you think that's going to play out with the induction data. Yeah, so thanks to triple seven, we've really tried to make it an optimized antibody. I think what we it's not is Libri with half-life extension, right? It does have an overlapping binding site and similar potency to lebrikizumab. We want to harness what we know has worked with IL-13, but then improve everything else about the molecule. It's on a new backbone, an IgG1 LALA backbone instead of an IgG4 backbone. That helps with a variety of properties for the antibody. It is concentrated at 180 mg/mL versus lebrikizumab at 125 mg/mL. Those things lead to positive things like COGS, et cetera, as well. Obviously the optimized PK profile is a key piece of it, which comes through the YTE amino acid substitution, which we've shown from our phase one data is able to extend the half-life to 77 days versus lebrikizumab at less than 25 days. Three times the half-life, but also decreased variability and other great PK properties as well. That optimization has led us to be able to test in the phase two trial reading out this year, 30%-40% greater exposures in the induction setting, but with almost 50% fewer injections. We're testing higher exposures because there's a good amount of data suggesting that there could be an exposure response that was not fully harnessed by lebrikizumab, but we can still do that with improved dosing for patients. Got it. With those higher exposures, Carl, I guess what gives you confidence that you're not going to run into any safety tolerability issues? Maybe you could talk through what you saw in the phase I healthy volunteer experience. Yeah. No, so great question, right? So a couple of things that we've looked at so far, right, which give us confidence that we'll be able to do this with a similar safety profile to what Libri and DUPI have seen, which has been very tolerable for patients. One is our healthy volunteer data. We went to doses of 1200 milligrams, right? So we do that not because we're going to use a 1200 milligram dose per se, but we want to fully explore the safety profile in these phase one trials. This is something obviously repeated across our other phase one trials too. To really understand the safety at these higher doses. We saw a very benign safety profile. Most common thing was headache, well-balanced across placebo and treatment cohorts. The next set of things is all related to what I would describe as a bad phlebotomist with a lot of blood draw related issues. Really benign, no conjunctivitis in that overall. The other thing we've seen is from Libri and DUPI, right, which conjunctivitis is the main thing here. Libri is kind of in the 10% range. DUPI may be more like 15%-20%. Neither of them saw a dose response or dose AE relationship or exposure AE relationship. Conjunctivitis for these really seems to be idiosyncratic in nature too. We think that going to these higher doses based on both our phase one data and what we know from Libri and DUPI shouldn't open up any new safety liabilities for us. Got it. You completed enrollment in that part A induction portion of the study. Maybe you could just talk a little bit about the patient population you enrolled, how you're treating, are you enrolling patients who have failed prior to Dupixent, and then help sort of frame expectations for that data readout. Yeah. We're running a phase two study still ongoing. It's a two-part study. One thing we wanted to really optimize was operational excellence in that study heading towards the goal that Jane mentioned, which is a launch this decade for APG777 in atopic dermatitis. It has both a proof of concept portion, which we'll be reading out mid-year, as well as a dose optimization portion, which we'll read out second half of 2026. The part A, the proof of concept portion, was fully enrolled. We announced that in early February. It was over-enrolled, 123 patients versus our target of 110 patients. That was really due to investigator and patient enthusiasm for the study. In less than a week after that enrollment completed, we started enrolling in the part B. For this study, we're really focused on rigorous IE criteria like Libri and DUPI did in their phase twos and phase threes. This is EASI 16 and above at both screening and baseline, which is a really key parameter in terms of making sure we get moderate to severe patients in the study. Other people have kind of taken different approaches to maybe make it a little easier to enroll, but I think that's sacrificing what we need, which is the understanding of how APG777 compares to the current standard of care, right, which is DUPI and Libri. Yeah, I was going to. Yeah, I guess with respect to. With Parin. Yeah. With respect to kind of how you're thinking about bar for success in the phase two, like what do you need to see to feel really confident in the 777 profile? Yeah. You know, so obviously we're testing higher exposures. That's a hypothesis we want to explore. However, what we've heard repeatedly kind of from the beginning, including I just came from Orlando where AAD was, is that what KOLs want to see, what investigators and prescribers want to see is similar efficacy and safety to DUPI. That's what they're looking for. Sure, I mean, they're not going to say no to greater efficacy, but that's what they're looking for with every three- to six-month dosing. That's transformative for them. That will kind of drive the needle. We hear that consistently, whether it's talking to KOLs one-on-one or any blinded market research that Jeff has done, that really drives what it is. We're setting that target because that's what we hear from the market actually matters. Anything on top of that, I think, is really icing on the cake. We're hearing the same thing from patients as well as importantly payers. Maybe Jeff, you can comment on what we're also hearing from payers on that profile of similar efficacy, but transformational dosing. Yeah. Payers, they understand that AD is not plaque psoriasis. There are not enough options for patients right now. When you look at a therapy that can be dosed every three to six months, it really increases compliance and persistency. You are getting the results you need, likely less switching. All of these things matter to a payer. Also, the fact that both patients and physicians, and I will reiterate Carl's point from AAD, the excitement from KOLs was overwhelming. They cannot wait for this option for their patients. When you have that much interest in a therapy, it is going to be used. The demand will be there. With that, payers, through blinded market research with the TPP that we are talking about, equal efficacy and safety have been crystal clear that they see this as a first-line biologic with equal access to Dupixent. Got it. That makes sense to me. I wanted to. Maybe the one other point that you asked, which was biologic experience, though the part A is biologic naive patients too. So no previous DUPI and Libri use. We wanted kind of the cleanest readout we could get there in terms of comparability too. Sorry, I know you asked that question. Yeah, that makes sense. Part B has a small biologic. Part B has a 20%, up to 20% biologic experience. Yeah. Got it. I did want to ask you, over the last several months, I think we've seen a number of phase two AD readouts where we have seen a bit of an elevated placebo response. Carl, I know you talked to and alluded to some of the quality control metrics that you've implemented into the study. Maybe could you comment on some of those competitor readouts and then maybe elaborate on some of the quality control things that you've implemented here? Yeah, right. I think that a couple of readouts, right? I think that I won't go too into that, but I think there's reasons that we've designed the study differently. Again, our goal here is to be comparable as much as we can, right? Libri and DUPI didn't do everything the same, but as much as we can to them. I mentioned IGA criteria is really a key piece, EASI 16 both at screening and baseline. We know Q32 allowed EASI 12 and above. The reason that matters is because that population from EASI 12 to 15 just has a higher placebo rate. We've seen this in other studies, right? They're like a more mild, they're still considered moderate per EASI criteria, but they're definitely more mild, have more cyclicality, et cetera. The other, I think, key piece that we've heard about, and I think maybe more related to Anaptys, right, which is use of topicals and how that's handled in analysis methods, et cetera. We are really strict about use of topicals. Anybody that used topicals in our studies counted as a non-responder. That is how Libri and DUPI handled it, how the EMA and FDA handled that, and how the most recent readout, which was ROCKET's phase three just a couple of days ago, handled it as well. They had really reasonable placebo rates exactly in line with DUPI and Libri. We've tried to implement a variety of things, IE criteria, analysis methods, or some pieces of it, but we've tried to think from the beginning about what our team mantra is, which is right patients from the right sites at the right pace. Not an emphasis on speed overall. Obviously, we want to be operationally excellent, but the emphasis is on a positive readout. That we think is going to come from the right patients. Site selection and region selection has been really important in this. 100% dermatology specialist sites that have done successful AD trials before in our study, a global footprint for the study, rigorous IE criteria, and then a ton of oversight and monitoring that includes taking baseline photographs of every patient enrolled in the study. That is kind of our honesty measure. That includes restricting how many patients a site can enroll. There is no kind of site that has too many and kind of weighs things. I think that maybe our sites and our CRO think we are like big brother. We are happy to be big brother in this case. That's what's kind of leading to this mid-year readout. We're excited about it. That's great. Yeah. That makes a lot of sense. Looking forward to that readout. Let's shift gears to APG279, which is the combination of your IL-13 and your OX40 ligand program. Just last week, you reported interim data from a phase one study of 990, the OX40 ligand, in healthy volunteers. You showed a 60-day half-life. I think you're aiming for a 21-day target there. Can you just talk about the importance of that data set and I guess how it informs how you guys think about that combination product. Yeah, right. Excited to have released data there. I think two real key pieces from it coming out of it. One is the ability to have kind of a co-formulated product that is in line with 777. One of the unknowns, like, well, what if the dosing frequency is different? Like, how do you adjust that too? The half-life and optimized PK profile and enabling every three to six-month dosing, just like APG777. Very excited about that and that ability to do that. The other piece of it is safety, right? As we're going towards multi-targeted approaches, right? Safety is going to be a really key piece. Here again, the most common finding for AEs was headache, right? I guess they just call that like being a normal human being. I think I had one yesterday. I was on a train from Orlando. It's probably headache-inducing, but balance across cohorts and nothing really else in terms of the findings overall. As we're leading towards our desire to put 777 and 990 in a single co-formulated product, APG279, right? Both of those things are really critical. The one addition, it wasn't from the clinical data that we released with this too, was the combination tox data. Our preclinical combination tox data showed no dose findings at any dose level, including the highest dose tested, which was 150 mg per kg per week of each agent, right? Really high doses. Those will give us really big margins going into the study head-to-head versus Dupixent. Great. Maybe kind of higher level philosophical question and debate we hear among investors in terms of multi-targeted, your approach, the combination approach versus sort of the bi-specific approach. I guess what are some of the advantages of that combination approach and how do you plan to really optimize the co-formulation of some of these product candidates going forward? Yeah. This is a great question, right? I think we had the ability to do and think about either of those, right? I have gone from a co-formulation angle. There is really, I think there are multiple things driving, but the two things that are driving it the most is one, the ability to get this stoichiometry or the ratios of the two drugs, right? Here, when you look at what you might want to do in terms of APG777 and APG990 together, it is unlikely that one-to-one is the optimized way to go forward here in our data, right? APG990, we see that 50 mg can get us to every three-month dosing, right? For which at a concentration of 180 mg per ml or greater, is only a small portion of what we can fit in a 2 ml auto injector. Therefore, the ratio between that and APG777 might be very different than one-to-one. We think that's a really important piece because our goal in combinations is to maximize efficacy, right? That, I think, can only be done when you're really thinking about how to get the ratios of these targeting two things at one time appropriate. We'll have kind of ability to do that by disease state too. What we might want to do in AD, for example, might be very different than what you want to do in, say, alopecia or something like that, which might have a different approach that you want to take the same drugs, but maybe different ratios there too. We have a little more flexibility in terms of that. The second is dosing interval, right? We really haven't seen a bi-specific to date really get beyond like four-week dosing. Even that is kind of at the extreme. A lot of people are trying different things to extend the half-life and maybe get to less frequent dosing. We just haven't seen it. We know through this approach that we're looking at every three to six-month dosing. As we push the AD space and these other spaces to every three to six-month dosing with our monotherapies, people are not going to want to go backwards to weekly dosing, right? We think those two are key pieces. They also lead to other things like decreased COGS, et cetera. I think those are the two things really driving our approach and our intentional selection of co-formulation over bi-specifics. Got it. That makes sense. Jane, you alluded to the plans for a phase one B, looking at 279 head-to-head versus Dupixent. Maybe you could just talk about, do you need to see, I guess, the 777 induction data to go ahead and, I guess, how much is that going to be informative in terms of dose selection? How are you thinking about dose selection for that study? Maybe talk about the importance of including Dupixent there as a comparator in that early, but important proof of concept. Yeah, we don't need to wait for the 777 data to start that. We've just guided to we will start the 279 head-to-head in a phase one, approximately 50-75 patients against DUPI with a readout of second half of next year. Carl, do you want to talk a little bit how we're thinking about dosing? Yeah, right. I think that here, our goal, we haven't disclosed dosing and aren't planning to today, but our goal here is to make sure in this first study, we walk away really knowing that it is better than a monotherapy. I think that's really key for us. To that extent, we really want to make sure we're covering both targets adequately. Taking kind of the most conservative approach because of the safety profile we've seen, because of the safety in that combination tox, right? We want to make sure we're saying we want to cover IL-13 at the level you need to cover it on its own and OX40 ligand at the level that you want to cover it on its own. Kind of a more conservative approach, not assuming any synergistic anything with it overall. Why we're comparing to Dupixent is really the key thing, I think, for us. I think this is what we hear from KOLs, et cetera, is a multi-targeted approach, whether bi-specific or co-formulation. If it's not beating a monotherapy, it's not relevant. We heard that repeatedly at AD this past week too. They're very excited about this because it will show them that going after these two targets at one time is actually meaningfully better than the monotherapy. Placebo-controlled trial here, kind of make whatever you want out of it, right? If it's kind of similar-ish to DUPI and Libri, right? It's not really something that people are interested in potentially prescribing in the future, which is what we're here to do. Yeah. It is important as part of our discipline on capital allocation, right? Get the answer upfront. Do not spend the money on a phase one that does not give you the real answer and then go into a phase two. Just as a reminder, we had really nice data at our R&D day in December showing from a preclinical point of view this thesis of combining IL-13 with OX40 ligand. It showed very clearly that by combining the two, you could continue to get the deep type two inhibition along with the breadth of type one, two, and three. The goal, of course, would be to get something that is more JAK-like in efficacy without any of the safety. It is a high bar, but it is what we are looking to do in terms of transformational for patients. Yeah. No, it seems like an important early, rather definitive signal finding. Jeff, maybe you could talk a little bit about strategically how you think about advancing 777 as a mono and then timeline-wise the potential for 279. Like how do these two things maybe play in the market simultaneously? Yeah, thank you for the question, Tom. First and foremost, we are laser-focused on launching 777 monotherapy in AD in this decade. It is crystal clear that physicians and patients really see the value in that three to six-month. We are going to quickly gain share with our monotherapy. I think to the point on 279, our combination, you asked about Dupixent and why Dupixent upfront. We will show the value of 279 above and beyond standard of care early on. We will also show the value of 279 against its component parts. Those things alone are what will allow us to make 279 a first-line biologic, just like triple seven or IL-13 will be a first-line biologic. Upfront, we will take share with triple seven. When we launch 279, we are elevating the efficacy bar. 279, as it comes out, we think will quickly take share from a couple of different areas. Number one, likely from JAKs. Number two, anyone on a monotherapy biologic that's not controlled. In time, we think that the market will transition not just in AD, but all of I&I over to combination therapy. We are very well positioned to be the leader in AD with our 279 combo. That makes a lot of sense to me. Okay. Let's switch gears and talk about you also have a TSLP antibody 333, and you're exploring combination with 777 and 333. Maybe just talk about your plans to run, I guess, monotherapy phase one B trials in asthma for 777 and 333, and then how you think about, I guess, defining what a combination path forward looks like for those two candidates. Yeah, I mean, I think 333 data, which is our TSLP coming out second half of this year, we'll look for something similar to what we just put out with APG990 in that what we really see the value in TSLP here is in combination potential too. We want to understand how together with 777, how they can be dosed at similar intervals, how they can be co-formulated. Obviously, safety in all these approaches is really key. We haven't announced plans for what the next trials look like, but we'll be doing that later this year. I'll just say a broad point, which is, and hopefully this is shown in our 279 approach, but also our 777 monotherapy approach. We're trying to produce trials that give us definitive answers on things, right? We're not trying to trickle out pieces of data that might be ambiguous or hard to read. I think we'll continue to do that moving forward. To Jane's point, it makes more sense from a capital allocation, but it also makes more sense from we have such a deep pipeline here that we want to be able to use the resources correctly. If it's not a one program, we've got plenty of other places to move to. We will not develop TSLP as a monotherapy. For the combination with triple seven, we're focused in respiratory. Given the alarm in biology, we don't think it makes sense to pursue it in AD or the derm area. A combo in respiratory, looking at both asthma and COPD, with a combo opportunity gives us the potential for broader efficacy as well as deeper efficacy across the patient population. That's the goal. Got it. That makes sense. Unfortunately, we're up against time, but I want to thank the Apogee team for joining us and sharing the updates. We'll certainly stay tuned to a lot of important data right around the corner. Thank you. Thanks for the time. Thanks, everyone.