Good morning and welcome to Apogee Therapeutics' Conference Call. At this time, participants are in listen-only mode. There will be a question-and-answer session after prepared remarks. To accommodate all attendees, we ask that questions be limited to one per participant. Please be advised that this call is being recorded at the company's request. I will now turn the call over to Noel Kurdi, VP of Investor Relations at Apogee. Noel, you may begin. Thank you, operator, and thank you all for joining us today. During this call, we'll be making forward-looking statements related to our current expectations and plans for the company, as well as our clinical and preclinical programs. These statements represent our views as of this date and should not be relied upon as representing our views as of any subsequent date in the future. Looking at our agenda today, CEO Michael Henderson will begin the call with an introduction to Apogee's latest developments and our goal of delivering a pipeline- in-a- product with our lead program, zumilokibart, or APG777. Chief Medical Officer Carl Dambkowski will then walk us through the phase I-B interim results of zumilokibart in patients with mild to moderate asthma. Then, Dr. Mario Castro, Professor and Chief of Pulmonary Critical Care and Sleep Medicine from the University of Kansas, will walk us through the science behind IL-13 inhibition for asthma. Before moving on to the Q&A, Michael will summarize our vision for building a leading I&I company and our transformative year ahead. The subsequent Q&A will be led by Michael, Carl, Apogee CFO Jane Henderson, and Chief Commercial Officer Jeff Hartness. We will also be joined by our KOL guest speaker, Dr. Mario Castro. I will now turn the call over to Michael. Thanks, Noel, and thank you all for your time today. Welcome back from the holidays. We're very excited to share these data as we look ahead to what we believe will be a transformational year for Apogee. Today's data reinforce the broad potential of our lead program, APG777. With the approval of its international non-proprietary name, zumilokibart, or zumi for short, we are moving rapidly to reaching more patients, with the program now further de-risked as a potential option for asthma. Today, we will walk through our positive interim phase I-B asthma results for zumi, which demonstrated a robust and durable effect on FeNO, comparable to DUPIXENT. Interim data show sustained suppression through 16 weeks for all patients following a single dose. Remarkably, the suppression remained through at least 32 weeks, or eight months, for the subset of patients for which longer follow-up is available, reinforcing our belief that zumi could transform dosing not just in atopic derm, but across a broad range of expansion indications, including asthma. Today's data represents the first of four critical readouts for Apogee this year. In Q1, we also plan to read out our 52-week maintenance data from Part A of zumi's APEX phase II study in patients with moderate to severe atopic derm. We look forward to sharing that data and believe it has the potential to showcase zumi's durability in atopic derm as well. In the second quarter, we look forward to data reinforcing zumi's 16-week induction profile when we read out our dose optimization study, APEX Part B in atopic derm. We exceeded our enrollment target ahead of schedule for this study, finishing with 347 patients, thanks to strong enthusiasm from both patients and physicians. This accelerated readout positions us to initiate our phase III studies this year, potentially accelerating our path toward a BLA. We believe we are well underway in establishing a potential best-in-class profile for zumi within the future $50 billion atopic derm market and are on a path to a planned potential 2029 launch with every three or six-month dosing. In addition to the mono therapy potential of zumi, we are evaluating fixed-dose combination approaches. The first of those, which combines IL-13 and OX40L inhibition, is APG279. 279 is currently enrolling a study in atopic derm head-to-head versus the market leader DUPIXENT. Given strong interest from patients and physicians, we have expanded that study following an interim safety analysis and remain on track to read out the study in the second half of 2026. We are also exploring the combination of IL-13 with TSLP inhibition via our fixed-dose combination APG273, and we'll share more details on our approach in respiratory conditions later this year. As shown with today's data in asthma, we see a future for zumi mono and combo approaches across numerous blockbuster indications. Taking a closer look at the potential for zumi, our pipeline and a product approach is backed by the scientific mechanism of IL-13 as a core driver of multiple I&I diseases. We have already showcased this in the derm setting with positive APEX Part A data last year. Reinforcing the data we're presenting today in asthma, we observed improvements across a number of comorbid conditions as part of our initial APEX Part A atopic derm data. Specifically, for patients with comorbid asthma or sinusitis in that APEX study, we observed improvements in their comorbid conditions of asthma and sinusitis as measured by improvements in ACQ-5 and SNOT-22, respectively. We believe this pipeline and a product approach has now been validated in respiratory conditions with today's positive phase I-B asthma results, and we look forward to expeditiously moving into further development. We are very excited by the potential of zumi, and the data we have seen to date further encourage our hypothesis that zumi can enable three- or six-month dosing for even more patients living with I&I conditions. With asthma data now in hand, we are entering late-stage clinical development in two of the largest I&I markets, asthma and atopic derm. Atopic derm is the largest and fastest-growing I&I market, with roughly 15% projected growth through 2030, while asthma represents the second-largest I&I market and an important comorbidity, with 30% of atopic derm patients having comorbid asthma. With clinical proof of concept for zumi in both indications, we believe we have the opportunity to deliver potentially best-in-class therapies across these large under-penetrated diseases that still have significant unmet need. I will now turn the call over to Carl to walk us through the phase I-B asthma data. Thanks, Michael, and thank you all for joining today. I'm excited to share the zumilokibart data in asthma today. zumilokibart achieved or exceeded all trial objectives. First, a single dose of 720 mg of zumilokibart was well tolerated, confirming the safety profile for this treatment as a monotherapy in patients with asthma. Second, the magnitude of FeNO reduction demonstrated by zumilokibart was in line with standard-of-care treatments such as dupilumab. Specifically, zumilokibart demonstrated a 45 parts per billion decrease from baseline, or 60% decrease from baseline in FeNO after a single 720 mg dose. Finally, zumilokibart's impact on FeNO was also durable, showing sustained FeNO suppression after a single dose for at least 16 weeks, which was the limit of follow-up available for all patients. Furthermore, in the subset of patients with data beyond 16 weeks, suppression was sustained through 32 weeks, which was the longest available follow-up data at the time of interim analysis. The sustained suppression of FeNO after a single 720 mg dose of zumilokibart supports dosing every three or six months in future studies. IL-13 biology has long been implicated as a key cytokine in asthma. However, previous trials evaluating lebrikizumab and IL-13 antibody in asthma patients did not always bear out positive results. We believe the subpar efficacy observed in these prior trials was driven by underdosing and broad patient selection. In these studies specifically, the highest lebrikizumab asthma dose used was more than four-fold lower than what is approved in atopic dermatitis, and enrollment was not enriched for patients with T2 inflammation. In contrast, the zumilokibart phase I-B asthma dose is modeled to have exposures at least three times higher than those achieved in lebrikizumab asthma trials and much more similar to successful atopic dermatitis trials for lebrikizumab. Additionally, we designed the phase I-B to enrich for patients with Type 2 inflammation by requiring baseline FeNO of 25 parts per billion or greater. The phase I-B was a double-blind placebo-controlled trial that evaluated the safety and tolerability of zumilokibart in 19 adult patients with mild to moderate asthma and a FeNO baseline equal to or greater than 25 parts per billion, which represents a population enriched for Type 2 inflammation. This trial also evaluated the magnitude and durability of FeNO suppression by zumilokibart, as well as other pharmacokinetic and pharmacodynamic endpoints. Participants were randomized three to one, receiving a single dose of 720 mg of zumilokibart or placebo on day one. FeNO is a well-established biomarker of Type 2 airway inflammation. FeNO has consistently shown the strongest correlation with asthma exacerbations across available biomarkers. Importantly, the FDA has suggested that FeNO may also serve as a potential surrogate marker of treatment response for asthma biologics, particularly those targeting the IL-4 and IL-13 pathways. Baseline characteristics and demographics outlined on this slide were generally well-balanced and in line with expectations for this patient population. In this study, zumilokibart has been well tolerated with a favorable safety profile across all patients. The safety profile is in line with expectations of therapies targeting IL-13 and what we've seen to date with zumilokibart in other studies. The only treatment-emergent adverse event observed in more than one patient was gastroesophageal reflux disease. There were two cases, and both were grade 1. There were no grade 3 or higher treatment-emergent adverse events or any serious adverse events. There were no observed cases of conjunctivitis or injection site reactions. The key analysis for this study was FeNO suppression, both in terms of magnitude and durability after a single dose of zumilokibart. zumilokibart both rapidly and durably suppressed FeNO through 16 weeks and demonstrated a maximum mean reduction of 45 parts per billion, with suppression sustained through week 16, which was the limit of follow-up available for all patients. Similar results were demonstrated when looking at percent change from baseline in FeNO, with a maximum mean percent reduction of 60% and durable changes through week 16. In looking beyond week 16, available follow-up data demonstrates continued suppression of FeNO on both an absolute and percent basis to week 32, the limit of our available follow-up. Durable FeNO reduction after a single 720 mg dose of zumilokibart supports a dosing strategy of every three or six months in future asthma trials. When viewed alongside a broad set of mechanisms and agents, the week 12 FeNO reduction observed with a single dose of zumilokibart is in line with effective and approved agents such as DUPIXENT and TEZSPIRE, which are dosed three to six times as frequently during the same period. The magnitude of FeNO suppression for zumilokibart was similar to that of Apogee's own IL-4 receptor alpha targeting agent, APG808. As mentioned, zumilokibart demonstrated durability out to 32 weeks post-dose for patients with available data. In contrast, APG808, which also incorporates half-life extension technology, began to show rebound in FeNO eight weeks after the last dose. We set out to design and execute a trial for zumilokibart that would demonstrate the ability of an IL-13 targeted agent to show FeNO changes in line with standard-of-care, as well as durability of those changes supporting at least every three-month dosing. To do this, the zumilokibart phase I-B trial in mild to moderate asthma patients enriched for patients with Type 2 inflammation and tested a higher drug exposure than previously used for IL-13 agents in asthma studies. The study achieved or exceeded all trial objectives, including demonstrating a well-tolerated safety profile, robust magnitude of FeNO suppression in line with standard-of-care agents such as dupilumab, and a durable FeNO suppression 16 weeks post-dose, which was the limit of follow-up data for all patients. Further, in the subset of patients who had 32-week data showed a robust and sustained FeNO suppression out to 32 weeks for those with data available past week 16. We also are observing positive trends for FEV1 and Type 2 inflammatory biomarkers for available data. We look forward to sharing further data from this trial at an upcoming medical conference. This data, we believe, is supportive of every three- or six-month dosing and of advancing zumilokibart in additional asthma studies. We plan to disclose additional plans for our asthma program later this year. Now I have the great honor of introducing Dr. Mario Castro, the Ellie Phillips and Leonora Carr Phillips Professor and Chief of the Pulmonary Critical Care and Sleep Medicine Division at the University of Kansas Medical Center. Dr. Castro is a widely recognized expert in asthma with over 300 peer-reviewed publications, including lead authorship on the DUPIXENT pivotal phase III QUEST study. I'll now turn it to Dr. Castro to help contextualize the zumilokibart results. Thank you. Hi, I'm Mario Castro at the University of Kansas Medical Center. Thank you, Carl. I'm thrilled to be part of this important day for Apogee. As demonstrated here, IL-13 we know is a key mediator in asthma. We know that it's one of the Type 2 cytokines, IL-4, 5, and 13, and this is one that has been targeted by a number of different biologics for asthma. We know that IL-13 drives a lot of those key features we see in severe asthmatics, such as mucus hypersecretion, airway hyperactivity, and eosinophilic inflammation. As demonstrated in this study, we demonstrate that the biopsies from patients with severe asthma, both atopic and non-atopic, had marked increase in message for IL-13. This next study we conducted as part of our severe asthma research program to study the key features of airway remodeling. We know that in airway remodeling, this includes epithelial thickening, subepithelial fibrosis, goblet cell hyperplasia, and increased smooth muscle mass. What we demonstrate here is marked upregulation of MUC5AC in the airway epithelium in patients with severe asthma. And this was also accompanied by a decrease in cilia-related genes in mucus clearance. This demonstrates the key role of IL-13 in terms of driving this disease process in terms of greater mucus production and decrease in mucociliary clearance. This also is corroborated by the study on the right-hand side, which demonstrates that the green staining is MUC5AC, the red staining being cilia. When you add IL-13 to epithelial cells, you see this marked diminution in the cilia and marked upregulation of MUC5AC. These key features of airway remodeling lead to airflow obstruction and hyperresponsiveness. Next, let's move on to the clinical studies that have been done with IL-13. You may recall lebrikizumab has been studied in previous clinical trials, but did not demonstrate a significant benefit. What we learned, though, in subsequent analysis in this study published by Jonathan Corren, is that it also depends on the subset of patients you select. As demonstrated here, if you target those with a high T2 expression, either by FeNO, 50 parts per billion or greater, or looking at blood eosinophils of 300 or greater, now actually lebrikizumab does work in reducing exacerbations in these patients with high T2 biomarkers. This again suggests that IL-13 inhibition would be effective in the right patient that has high T2 inflammation. So to summarize, what we've briefly demonstrated here is the key role that IL-13 plays in asthma. We know that this is really a key player, not only in the disease process, but in the remodeling process that leads to progressive disability in our patients, as demonstrated by their chronic airflow obstruction, repeated exacerbations, and lack of control. This post-hoc analysis that we shared with you with lebrikizumab, another anti-IL-13 blocker, did demonstrate that if you select the right patient with the right monoclonal antibody, anti-IL-13 in this case, that there was a significant reduction in asthma exacerbations. I am thrilled to be part of the Apogee data in discussing this with you, the phase I zumilokibart interim data. This phase I study demonstrates a significant and durable improvement in lung function in this phase I study and suppression of exhaled nitric oxide with a single dose, and also within acceptable safety profiles when we expect from IL-13 inhibition in appropriately selected populations. These results are very encouraging, and I look forward to continued work with the Apogee team as they develop zumi for our patients. I will now pass the call back over to Michael for closing remarks. Thank you, Dr. Castro. The growing asthma biologics market will soon exceed $15 billion and is evolving towards agents that offer longer dosing intervals. DUPIXENT has become the market leader, given its unique position as the only biologic approved for both asthma and atopic derm, but it is dosed every two weeks. We believe zumi has the potential to become the leading Type 2 inflammatory therapy, pairing robust disease control in asthma and atopic derm with an improved dosing profile that could transform patient care. We believe zumi is well-positioned to expand into additional indications and realize its potential for pipeline and a product. Existing therapies face inherent limitations in balancing efficacy with dosing frequency. Zumi has the potential to change that and could be the first long-acting biologic approved for both asthma and atopic derm, offering dosing every three or six months and the opportunity to transform the treatment paradigm by reducing the burden of frequent injections for patients. With APEX atopic derm readouts anticipated in the first and second quarters of this year and the planned initiation of the ASPIRE trial in asthma, zumi is positioned for expansion across several of the largest I&I markets. We see further potential in EOSinophilic esophagitis, COPD, and a number of Type 2 inflammatory conditions. Looking ahead, we are thrilled to have kicked off 2026 with our first data set for zumi. This marks the beginning of what we believe will be a transformational year, as we plan to deliver multiple significant clinical data readouts across our mono and combination programs and advance in the late-stage phase III development. We will continue to report results from our zumi program throughout the year, with APEX data in atopic derm expected in Q1 for 52-week part A maintenance and Q2 for 16-week part B induction. The second half of the year will be pivotal for us as we share the first data for APG279 in the head-to-head trial against DUPIXENT and initiate our first phase III trial for zumi in atopic derm. Thank you all for joining us today. With multiple catalysts ahead and strong clinical momentum, we are excited about the year to come and the opportunity to deliver potentially best-in-class medicines that can make a meaningful difference for patients across a broad range of I&I diseases. I'll now hand the call back to the operator to begin the Q&A. To help us manage the discussion, we ask that each caller please limit themselves to one question. Thank you. As a reminder, in order to ask a question, press star one on your telephone keypad. We'll take a brief moment to get the Q&A roster compiled. Your first question comes from the line of Seamus Fernandez from Guggenheim. Your line is live. Oh, great. Thanks so much for the question. So actually, I'm going to go a little bit more in a commercial direction here. Can you guys just comment and give us your thoughts on the impact that both a long-acting treatment in asthma that could also be used as a combination in concert with an atopic dermatitis label, what would that mean from a commercial perspective in your view? Largely because it's been our view here that IL-13 would work in asthma, that this would be highly differentiating, and that it also basically opens up a much broader opportunity to target allergists and pulmonologists. But I think there may be some other commercial benefits beyond that as well. Thanks so much. Thanks, Seamus. I appreciate the question. I'll comment briefly and then hand it to Jeff. We felt from the beginning that given kind of the atopic triad, many of these patients that have atopic dermatitis, up to 30% of them and even more in the pediatric setting have comorbid asthma. So the ability to have the conviction that our agent will work for both atopic derm and asthma and be potentially the only long-acting biologic that will have proof of concept and both on the label is quite differentiated from other drugs in development. Jeff and his team have spent a lot of time kind of mapping this out and the impact it could have. So Jeff, I'll hand it to you to comment on the different advantages this could bring us. Yeah, thanks for the question, Seamus. I think it's important to note that right now in the biologic asthma space, DUPIXENT is the market leader and that is in spite of being fourth to market and in spite of having every two-week dosing. W e believe the reason that they're the market leader is, in fact, that they have both the indications in AD as well as asthma and with Michael's point of 30% of these patients having comorbidities, that is a really important space that those patients are currently just getting DUPIXENT. So we will be able to walk into that space, quickly have an impact with being the only product with both indications and having the extended dose options that we plan on having. I think secondarily, aside from just driving that volume and that revenue, I think it's important when you think about it from an access perspective, we have been clear about our confidence level in having early access for zumilokibart with payers for atopic dermatitis. What this allows us is to strengthen that position, not just by having a line extension within the contract to also cover asthma, but it strengthens our position because, as a reminder, these two indications are, in fact, the largest indications that DUPIXENT has, both by volume and revenue. So it strengthens our position to really get not just the access, but get it at the right price. Your next question comes from the line of Akash Tewari from Jefferies. Your line is live. Hi, this is Phoebe for Akash. Thank you for taking our question. Just looking towards Sanofi's TSLP and IL-13 bispecific asthma readout in this half of the year, do you think, A, this can hit in the all-comer population here and in COPD? And B, what level of benefit do you have to show in the EOS less than 150 subgroup to consider this sort of clinically meaningful? Thank you. Yeah, thank you, Phoebe. I'll hand it off to Carl to speak to that. Yeah, thanks for the question. I think, yeah, obviously, we're tracking closely with Sanofi's TSLP IL-13 antibody in addition to the zumi monotherapy data we're showing here, which, as Jeff and Michael hit on, we think will be a huge benefit for patients as a monotherapy itself. We're also looking into the combination of zumi and APG333, which we call APG279, so the fixed dose combo of IL- or sorry, 273, the fixed dose combo of IL-13 and TSLP as a potential benefit for patients. We do think the main benefit of the combination therapy, as you suggested, is in the non-T2-enriched population, meaning in the population that is, for example, less than 150 EOS. Mechanistically, we're encouraged by what the combination could show there. And so we think that Sanofi and down the line ourselves could hit both in an all-comers population as well as in a COPD population, which we know is much more heterogeneous in terms of cytokines and disease course as well. We think the bar in the EOS less than 150 is somewhere between 40% and 50% reduction in AERs, which would really show benefit there more similar to what DUPI and TEZI have shown in the T2-enriched population. And so that's what we'll be really looking for there, both in the Sanofi data and in the future for our own combination. Your next question comes from the line of Tyler Van Buren from TD Cowen. Your line is live. Hey, guys. Good morning and congratulations on the tremendous results in asthma here. Regarding the ASPIRE trial that you're planning for, I don't believe you guys said whether it would be phase II or phase III. So considering the fact that the AD phase II program is exploring dose ranging and that you guys like to run fast in development, is it possible that the ASPIRE trial could be a pivotal trial in asthma? Thanks, Tyler. I appreciate the question. This data is hot off the press. We're evaluating the most expeditious path and how to move forward. Obviously, we're quite excited about this data and thinking about how do we get this approved into patients as quickly as possible, but more to come on the trial design later this year. Your next question comes from the line of Alex Thompson from Stifel. Your line is live. Great. Thanks. And congrats on the data as well. I guess maybe to the specific data set itself, I wonder if you could comment on how representative you think this patient population is relative to how you might think about enrolling your next study. And then also if you could comment on the placebo response you saw on FeNO and any underlying changes in background therapy, etc., or what could have driven that. Thanks. Yeah. Thanks, Alex. Our EOSinophils here came in right around 300 on average. So we saw a nice range kind of 150, 100 +, which pretty closely matches the DUPIXENT label of EOSinophilia. And that greater than 150 benefit or about 2/3 of asthma overall, we feel like it was a fairly representative population of that Type 2 as defined by EOS greater than 150 population. And Carl, do you want to speak to anything else? Yeah, no, agree. I think that our goal here was to do a T2-enriched population, but one that would be representative of what we would do in future trials, and we saw almost all patients in this cohort were EOS 150 or greater, which we think is fairly representative there. As Michael said, the average EOS count was around 300, which is a little lower than what we've seen in DUPIXENT's trial, which would have been anywhere from the mid-350s to high 400s, depending on the trial, so overall, we feel it's a T2-enriched population that would be representative in that nature of what we would do in future studies. On the second part of the question in terms of placebo response, I think we're seeing two things here. One, we had a fairly high baseline FeNO, as you can see. So there's just some variability that we see overall in terms of the placebo arm as well. And then I think the small n is contributing there as well. I think whether you look at it on an absolute or placebo-adjusted basis, I think the FeNO results to us demonstrate what we wanted to in this study, which is that an IL-13 therapy with the right dose and the right patient selection can be as effective as Dupilumab and other effective agents here. And then obviously, we're really excited about the durability too. But whatever way you look at it, I think it's showing that when you design the right study, IL-13 should be as effective as IL-4 receptor alpha targeting. Your next question comes from the line of Julian Harrison from BTIG. Your line is live. Hi, good morning. Congratulations on these data, and thank you for taking my questions. Keeping in mind patients in the study only received a single dose of zumi, do you have any thoughts or expectations with regards to deepening responses following multiple doses in future studies? And then I think I know the answer to this next question, but just to clarify, do you necessarily have to have the best in category biologic in asthma for commercial success here? Or is it your view that first-in-class dual labeling is a sufficiently positive outcome long-term? Thank you. Yeah, thanks, Julian. I appreciate the questions. I'll start, and then I'll hand it to Jeff to speak to what we think will be needed for commercial success piece. In terms of deepening following multiple doses, I think we look forward to running additional studies where we'll test, obviously, multiple doses and multiple dose regimens to just see how disease control could be over time. We do know that in asthma, COPD, and respiratory conditions in particular, the more that you can have a drug on board to the fewer kind of trough levels you can have to prevent exacerbations or any risk of target coverage not being maintained for whenever any assault on the respiratory system could happen is key. And of course, in the real world, that has led to much improved adherence and outcomes for longer-acting agents and hence our commercial success, which I think feeds into the second part of the question that I'll hand over to Jeff. Yeah, thank you, Michael. And thanks for the question, Julian. I would say to expand on that, I think first and foremost, having the dual labeling and the expanded dosing is, in fact, key to the commercial success. I think when you look at DUPIXENT for asthma and you look at their adherence rates in the first year, they're extremely low in the 55% range. And with asthma, as you know, this really does the adherence rate really does impact outcomes. In fact, it impacts overall healthcare costs with hospitalizations and emergency department visits as well. So we believe that if we have a similar efficacy and safety profile with the expanded dosing and the dual labeling, this positions us extremely well to become the market leader in both indications. Your next question comes from the line of Geoff Meacham from Citi. Your line is live. Hey, guys. This is Mitch on for Geoff. So you also saw positive trends in FEV1. Of course, it's a small n. Can you provide more qualitative or quantitative color on the magnitude of this FEV1 change compared to the changes seen with DUPIXENT in some of the similar studies? Yeah, no, thank you for the question. I'll hand it off to Carl to just speak to kind of qualitatively what we saw. We are going to keep the quantitative piece for later on at medical conferences as we have a lot of data that we're still working through here and are excited to share in the future. And then I would love to ask Dr. Castro also comment on why it's exciting in this population to see FEV1 even with a small patient population. Yeah, as Michael said, I think what we're really encouraged by and what we weren't expecting in the study is positive trends in FEV1. Obviously, the main goal of this study and why we're releasing the data today was to show the FeNO changes over time, both in magnitude as well as durability. But we have more data we're working through that we'll release at medical conferences later this year as well as help inform our design of the Aspire trial, which we'll release more on later this year. So I'll turn it over to Dr. Castro, and maybe I'll ask him to comment on two things. One is why FEV1 matters, but also why FeNO has kind of been maybe more important and kind of the best link to future studies as well too. Dr. Castro, if you could take it. Sure, Mario Castro. In all of our asthma trials, FEV1 has always been kind of the gold standard, and to see FEV1 improvements in this patient population in a phase I study is actually quite positive in that we're seeing it already as a signal. Sometimes we don't see this until later phase II studies, so I think this is in line with what we expect to see in subsequent pivotal studies that are going to be done. The second part of that question in terms of the FeNO as a biomarker and it being important predictive of future response, when we think about this pathway, the IL-13 pathway, it's been pretty consistent as a biomarker that is predictive of other outcomes that are going to be important down the road, not only lung function, but also reduction and exacerbation. So we're quite impressed by this magnitude of reduction in FeNO and that that should, again, correlate with what we'll see with other clinical outcomes. Your next question comes from the line of David Nierengarten from Wedbush Securities. Your line is live. Hey, thanks for taking the question. I just had one for Dr. Castro. I know it'd be off-label use, but if you have treated patients who maybe have been who fit the profile of the patient who would benefit from IL-13, if you've treated any of your patients with EBGLYSS and if the results were consistent with the post-hoc analysis from the previous studies? Thanks. Could I clarify off-label use in terms of what type patient? Treating asthma. Yeah. And treating the patients you might expect would benefit with the high Eosinophils or other markers. Using a drug like this one or? EBGLYSS. Yeah, using EBGLYSS, IL-13. Oh, okay. Yeah. So really, I think I'm impressed by the post-hoc data that I shared with you from Jonathan Corren's paper in that when you select the right patient population, then we see that pretty marked reduction in exacerbations and improvement in lung function. So I haven't used this off-label. It's not really been available for us to use in that format clinically, but that data does suggest that this would have the effect that we expect. Got it. Thanks. Thank you. Your next question comes from the line of Brian Abrahams from RBC Capital Markets. Your line is live. Hey, guys. Congrats on the data, and thanks for taking my question. I guess more broadly speaking, I was wondering if you could maybe comment a little bit more about the PKPD that you're observing here versus what you've seen in your prior studies and maybe how to apply the safety findings and the durability here to other indications like AD? Thanks. Yeah, thanks, Brian. Appreciate the questions. So here, I think the PKPD is very much in line with what we've seen with our other indications. It continues to be a very well-behaved antibody, right? Very low ADA incidence, none observed here. And kind of that rapid and then deep sustained durable reduction in different biomarkers or functional endpoints. On the safety side, I do want to caution that, right, DUPIXENT, IL-4, kind of IL-13 inhibitor pathways, they do see conjunctivitis, as do we in the context of derm conditions, but a much lower rate in the context of asthma, EOE, COPD expansion indications that are non-derm. So I think what we're seeing here is a continued very well-behaved drug that doesn't see kind of that conjunctival phenomenon that's known by physicians to occur solely in the context of derm. I think when we look at kind of our overall safety profile today broadly, we continue to have a very well-behaved, well-tolerated, very safe mechanism and antibody, as would be expected with the class. Very helpful. Thanks. Your next question comes from the line of David Huang from Deutsche Bank. Your line is live. Hi there. Thanks for taking my question. So I believe you mentioned with the APG808 molecule, your IL-4Rα, you had looked at that, and you saw a bounce back in FeNO at eight weeks. And here, obviously, the durability is going out to 16 weeks plus with the IL-13. Could you just comment on if that is sort of in line with your expectations around kind of the biology here and the durability with the IL-13, the additional durability? What is driving that versus the less with the 808 molecule? Yeah, I appreciate it. Last year, we ran this very similar experiment with 808. And I think what gives us a lot of excitement and conviction in the durability that we see with zumi that we're sharing today is that we did not see that with our IL-4 receptor alpha half-life extended optimized antibody. So there is a high amount of target-mediated drug disposition with receptor-bound targets. So even with our view is that with our 808, we would need about two injections to even get to every two- to three-month dosing. Whereas here, following this single dose, right, we're out to 16 weeks for all patients or eight months for those that we have follow-up with that kind of without the bounce back being seen. Eight months versus eight weeks for us is a pretty clear advantage when we think about the ability of an IL-13 mono or future combos versus IL-4 backbone, either monos or bispecifics. Because of the inherent biology and high target concentration of IL-4 receptor, it just is a shorter dose interval. Your next question comes from the line of Joe Catanzaro from Mizuho. Your line is live. Hey, great. Appreciate the update. Thanks for taking my questions. Maybe one from me somewhat related to the PKPD relationship. I'm wondering if the durability of FeNO reductions out to 32 weeks aligns with exposures at that time point that you would expect to be efficacious. And if so, how much beyond week 32 do you expect exposures to remain above that efficacious level? Thanks. Yeah, thanks, Joe. I'll hand it off to Carl. Yeah, so great question. Thanks for that. I think that part of the design for this dose in zumi here is that the 12-week exposures align with Q12-week steady-state exposures of zumi in our AD study, and the 24-week exposures align approximately with the Q24 every six-month dose in the zumi maintenance study, which we'll be releasing data on in Q1. I know that doesn't exactly answer your question, but just saying how we got there too, and an open question for us, and based on all the data we have, is do you even need those exposure targets to maintain responses out to three and six months or maybe beyond? So, I think we're very encouraged by the exposures we're seeing here and the durability of response out to 32 weeks or eight months, as Michael said, and it opens up questions of exactly how much drug you need to maintain these responses, not only in asthma as we're seeing with FeNO here, but for our maintenance data in AD in Q1 of this year. That's helpful. Thanks for taking my question. We have run out of time for questions in the question- and- answer session. And with that, the question- and- answer session has concluded. Thank you for joining Apogee Therapeutics' Conference Call. Have a great day.