Thank you for standing by. My name is Kathleen, and I will be your conference operator today. At this time, I would like to welcome everyone to the APG 990 phase I Interim Readout Presentation. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. Thank you. I would now like to turn the call over to Noel Kurdi, VP of Investor Relations. Please go ahead. Thank you, Operator, and thank you all for joining us today. During this call, we will 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, our CEO, Michael Henderson, will begin the call with an introduction to today's APG 990 phase I healthy volunteer trial interim results and our planned combination strategy for this program. Following, our Chief Medical Officer, Carl Dambkowski, will discuss the scientific rationale for APG279, our combination of APG777 and APG990, and the APG990 phase I interim results. Kristine Nograles, Senior Vice President of Clinical Development, will then walk us through the plans for the APG279 clinical development program. Before moving to Q&A, Michael will summarize our vision for building a leading I&I company. The subsequent Q&A will be led by Michael, Carl, and Apogee CFO, Jane Henderson. I will now turn the call over to Michael. Thanks, Noel, and thank you all for the time today. We're excited to share positive interim results for our third program, APG990, and the implications for our combination program of co-formulated APG777 and 990, which we refer to as APG279. Apogee was founded to create best-in-class therapies for people living with I&I disorders, with an initial focus on atopic dermatitis, asthma, EoE, and COPD. Patients living with these indications have limited treatment options, often requiring injections as frequently as every one to two weeks. We believe these patients deserve new options with better efficacy and more convenient dosing. Today's positive interim results for 990 bring us one step closer to achieving this. Atopic dermatitis is a future $50 billion market, and we believe that Apogee is well-positioned to transform the treatment paradigm. All of our programs, including our combination approach, have the potential to be dosed every three months or longer during maintenance with just a single 2 mL injection. Patients and their physicians tell us this innovation alone would be transformational. But we also have three key efficacy readouts in atopic derm starting in the middle of 2025 through 2026 that each have the potential to unlock greater efficacy as well. First, in the Part A portion of our phase II study reading out in the middle of this year, we are testing 30%-40% higher exposures of drug levels of 777 compared to Ebglyss. Multiple pieces of evidence suggest these higher exposure rates could lead to better efficacy. Second, in the Part B portion of our phase II study, we are testing even higher exposures than in Part A to fully explore the potential of the IL-13 mechanism so we do not leave any remaining efficacy on the table. With our combo, which will be the focus of this call, we will be attempting to demonstrate better efficacy than the market-leading biologic Dupixent, and are testing our combination head-to-head. Lastly, we are well-capitalized to move as quickly as possible to bring these therapies to patients with cash into 2028 that should enable us to deliver each of these important readouts. This is an enormous opportunity that cannot be overstated, and we have the capital and team in place to move quickly. The next several quarters should be very exciting for us. APG279 is our combo program for atopic derm that combines 777 and 990, two antibodies that have been engineered for best-in-class properties against clinically validated targets and share an overlapping epitope with similar potency to lebrikizumab and amlitelimab, respectively. Both antibodies are Fc-engineered for extended half-life. For 777, final phase I PK demonstrated a 77-day human half-life. That is three times longer than lebrikizumab. For 990, today's phase I interim data demonstrated an approximately 60-day half-life. That is 2.5 to 3 times longer than amlitelimab. The exceptional PK demonstrated by both molecules, along with successful co-formulation at high concentration, could enable every three and six-month dosing for 279 with just a single 2 mL injection. By combining two of the most validated targets, IL-13 and OX40 ligand, 279 also has the potential to achieve best-in-class efficacy in atopic derm. At our R&D Day last December, we announced preclinical proof of concept for 279, which, as you can see here, demonstrates broader inhibition of Type 1, 2, and 3 inflammation compared to monotherapy. Later this year, we're excited to put 279 to the test in a head-to-head trial against Dupixent, with initial data expected in the second half of 2026. Now, I'll hand it off to Carl to dive deeper into the scientific rationale behind 279. Thank you, Michael. I'm thrilled to be here this morning to discuss our combination for atopic dermatitis and the APG990 data supporting this approach. We know that atopic dermatitis and other inflammatory diseases are heterogeneous, with broad cytokine involvement. Clinical data from Dupixent and E bglyss, which target Type 2 inflammation, as well as multiple preclinical and translational medicine studies, support that Type 2 inflammation and IL-13 specifically is the key driver of atopic dermatitis pathophysiology. Amlitelimab, on the other hand, which targets OX40L, has broader inhibition, inhibiting Type 1, 2, and 3 inflammation. But both biomarker and clinical data support that this inhibition is partial, showing lower clinical efficacy compared to Dupixent and E bglyss in non-head-to-head studies. Targeting IL-13 with greater exposures than E bglyss may allow for improved clinical outcomes, a hypothesis we are testing in our ongoing phase II trial of APG777 with a readout mid-year. Beyond that, though, we believe there is further potential in combination therapy. JAK inhibitors like Rinvoq illustrate this potential. They show deep inhibition of all three inflammatory subtypes and deliver strong clinical efficacy. But JAK inhibition also leads to safety liabilities, as evidenced by their black box warnings. APG279 could provide a significant improvement in clinical outcomes without the safety liabilities of JAK inhibitors. APG279 broadens the inhibition profile compared to biologic monotherapy approaches to include not just Type 2, but also Type 1 and 3 inhibition, potentially approaching JAK-like efficacy. At our R&D Day last December, we shared data demonstrating preclinical proof of concept for APG279, including the potential for broader and deeper inhibition of Type 1, 2, and 3 inflammation. As you see in the heat map on the right, lebrikizumab and dupilumab both provide deep Type 2 inhibition, while amlitelimab provides broad inhibition across Types 1 through 3 in inflammation, but not the depth at Type 2. Only APG279 inhibition approaches JAK-like activity on key inflammatory biomarkers. Importantly, our GLP toxicology study of APG279 in non-human primates supports that we may be able to achieve this JAK-like inhibition of key inflammatory markers while maintaining the well-tolerated profile that has been exhibited by APG777 and APG990 individually to date. In this three-month toxicology study, APG279 was well tolerated with no findings at any dose level, including the highest dose tested of 150 mg/kg of each individual monotherapy. In contrast, in non-head-to-head GLP toxicology studies, JAK inhibitors approved for AD saw cytopenias, decreased organ weight, increased thymomas, tachycardia, or hypotension. The APG279 toxicology study results, with no toxicity observed at any dose level, is a key outcome for the combination and supports our goal to approach JAK-like efficacy with APG279 without the safety liabilities. We not only want to have the potential for APG279 to be safe and to deliver best-in-class clinical efficacy, but we want it to be patient-friendly as well. We have achieved an APG279 co-formulation that is stable at high concentrations, injectable in a comparable time to Dupixent, and retains the potency of the two antibodies. Based on this and the best-in-class PK we've seen for APG777 and APG990, we believe we will be able to target a dosing regimen of APG279 as a single 2 mL injection given every three and six months in the maintenance setting of atopic dermatitis. Now we'll walk through the APG990 phase I healthy volunteer data supporting our ability to potentially have APG279 delivered as a single 2 mL injection just two to four times per year. When designing the phase I study for APG990, we laid out clear goals for what we needed to achieve in terms of safety, PK, and exposure targets, particularly with regard to APG990's potential for use in combination with APG777. Regarding safety, all tested doses up to 1,200 mg were well tolerated based on all available data at time of data cutoff. Moving to our second goal, we observed a well-behaved PK profile across all cohorts. While our target was at least a 21-day half-life, we exceeded this by a wide margin with an approximately 60-day half-life. With regards to maintenance dosing, our results today support the potential for every three and six-month dosing with relatively small doses of APG990, enabling APG279 to potentially be delivered as a single 2 mL prefilled syringe or autoinjector every three and six months in the maintenance setting of atopic dermatitis. We're pleased with these results for APG990 and what they mean for our APG279 combination program and patients with inflammatory conditions. The data we'll discuss today is from our ongoing phase I single ascending dose healthy volunteer study, which is testing doses up to 1,200 mg. The trial is fully enrolled, and today we'll be presenting interim data on safety and PK. Demographics were generally well-balanced across cohorts. APG990 has been well tolerated with a favorable safety profile across all cohorts, including doses up to 1,200 mg. The safety profile is in line with expectations for therapies targeting OX40L and is supportive of continued development. Adverse events have been mild and generally unrelated to study drug. There have been no cases of pyrexia or chills. There have been no serious adverse events and no dose-dependent trends in AEs. APG990's PK profile has been favorable. The half-life of APG990 is approximately 60 days, which is approximately 2.5 to 3 times longer than amlitelimab's published half-life of 20 to 24 days. Moreover, APG990 generally demonstrates dose proportionality and low variability. Here we have modeled exposures from an APG990 every three and six-month dosing regimen. As you can see from the blue traces, both regimens are modeled to have comparable exposures to that of amlitelimab. Importantly, based on the best-in-class PK profile we've seen for APG990, we have achieved these exposures at relatively low doses. This leads to the potential for APG279 to be dosed in a single 2 mL injection every three and six months in the maintenance setting of atopic dermatitis. I'll now hand over the call to Kristine Nograles, our Head of Clinical Development, who will discuss the APG279 clinical development plans, including our plans to launch a phase I-B study this year, putting APG279 head-to-head versus Dupixent. Thank you, Carl. We will now discuss next steps for clinical development of APG279 in atopic dermatitis. Supported by today's positive phase I interim results for APG990 and favorable combination toxicology showing no adverse findings for APG279, we plan to initiate a phase I-B study of APG279 head-to-head against Dupixent. This study will evaluate the safety, PK, pharmacodynamic effect, and efficacy of APG279, which combines APG777 and APG990 to target orthogonal mechanisms that are both clinically validated and well tolerated in AD. We expect to initiate this study later this year and plan to randomize 50 to 75 patients with moderate to severe AD to either APG279 or standard of care Dupixent. We selected Dupixent as the comparator arm in this study as we believe that it is important to demonstrate the potential for improved efficacy over currently available treatments. Efficacy readouts will be at weeks 16 and 24, providing two opportunities to demonstrate the potential for better efficacy with APG279. We expect to report initial data from the phase I-B study in the second half of 2026. Our goal is that this phase I-B study will demonstrate three things. First, that APG279 has an acceptable safety and tolerability profile to progress to later stage trials. Second, that APG279 shows broader pharmacodynamic effect on key AD biomarkers of types 1, 2, and 3 inflammation. And third, that APG279 demonstrates a promising efficacy profile compared to standard of care Dupixent early in the clinical program prior to progression to later phase trials. We are very excited to initiate Apogee's first combination program this year. We believe we have the potential to show improved clinical outcomes when taking an orthogonal approach with two of the most validated targets, IL-13 and OX40L, in patients with AD, while minimizing the injection burden to every three-month dosing or better in the maintenance setting. I'll now turn the call back over to Michael for closing remarks. Thanks, Kristine. We are building a next-generation biotech company with plans to deliver innovative medicines across three waves of innovation. Our nearest-term opportunity is to prove the potential of APG777 as a best-in-class therapy for moderate to severe atopic derm, starting with the readout of Part A of our phase II trial in the middle of this year. Beyond atopic derm, IL-13 is implicated in more than 10 other indications. These represent opportunities for us to extend the impact of 777 for a greater number of patients. We've announced the first two of these indications that we will pursue: asthma and EoE. An initiation of proof of concept studies in those indications is expected to begin this year for asthma and next year for EoE. Finally, we are at the forefront of bringing the innovation of combination therapy to AD. As we detailed today, APG279 has the potential to approach JAK-like efficacy in atopic derm, and we expect to begin a proof of concept trial testing 279 head-to-head against Dupixent this year with a readout in the second half of next year. We've seen quarterly dosing transform other JAK markets such as psoriasis. We believe Apogee's therapies can similarly transform the atopic derm market and are excited that with today's data, both our monotherapy and combination approaches have the potential to be dosed as a single 2 mL injection just two to four times per year. We've been excited by the momentum seen thus far across our clinical programs, and as we look ahead to the next two years, that momentum continues. We expect seven additional clinical trial readouts over the next 24 months, including the 16-week proof of concept readout for Part A of our phase II trial of 777 in the middle of this year with additional readouts next year. Today's 990 readout is an important step in this combination approach. We look forward to continued progress in these programs with multiple data readouts to come. Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press the star one again. If you're called upon to ask your question and listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question. Again, please press star one to join the queue. Your first question comes from the line of Seamus Fernandez of Guggenheim Partners. Your line is now open. Oh, great. Thanks for the questions. And, you know, congrats on the excellent profile of 990. Maybe the first question is really, if you can just help us understand, it seems like, you know, the company has continually executed their profile of recruitment and then study and then data presentation faster in most cases. And it seems like the second half of 2026 might be a little bit long. Are you just kind of providing extra cushion for execution of that study versus Dupixent, or are there specific, you know, workup dynamics that need to be executed on before the official initiation of the 279 study? And then, you know, two just very quick additional questions in terms of controversies that investors have been dealing with. First, just hoping that you could provide, I know you have done this in the past, but maybe to remind investors, all of the dynamics that you've brought into play for the 777 induction phase II to really manage the placebo response in that study and what your expectations are along those lines. And then just the second question on a similar topic, maybe just to remind investors how challenging it is to actually generate, you know, assets with a profile like what you are delivering with 777, 990, and your anti-TSLP as well. Thanks so much. Great. Thank you, Seamus. I appreciate the questions. And we'll endeavor to hit on all of them, but let us know if we miss anything. First, on the timing piece, you know, we continue to be excited by the enthusiasm that we see from the physicians and sites and patients that are enrolling in our studies. You know, that did allow us in the past to move up the upcoming 777 Part A readout from originally second half of the year to middle of this year, which we continue to be, you know, very excited about. I think, you know, it's just too soon to comment on the guidance beyond what we already have around 279. You know, we will look to provide updates in the future, you know, if and when we have the sufficient data to do so. You know, we're just kind of using that as a point, though, that, you know, between Part A, middle of this year, and then Part B and 279 coming next year, right, three efficacy readouts in atopic derm that could prove us to have, you know, potentially a best-in-class drug by the end of next year, which, you know, we're very excited about that setup. Your second piece I'll hand to Carl on the, you know, phase II and all that we've done to mitigate placebo rates. You know, I will say that to help assist investors, we have added a few slides just to our corporate deck online in the appendix where we've shown recent trials, really actually every trial since Dupixent with similar inclusion and exclusion criteria to us in terms of EASI baseline of 16 and above. Right, investors can go there and see that trials designed in that way actually have pretty consistent placebo responses. While there were, you know, last year some placebo responses that were seen higher in some less severe patient populations or, you know, in different protocols, we endeavored to stick to what lebrikizumab and Dupixent and others have done. And that has across a variety of endpoints led to, you know, pretty reliable placebo responses over the past 10 years. So again, right, the data doesn't lie. Encourage folks to look at that because I think the charts speak for themselves. Beyond that, we have taken a number of measures in our trial. I'll hand it to Carl to hit on some of those. Yeah. And so, you know, since the beginning of the design of the trial, we've really been thinking about how we make sure that we, you know, have a reasonable placebo rate for APG777- 201. You know, there's kind of three key areas that we focused on in doing that and probably a lot of other details we could add to this. But from a high level, you know, the first piece is really site and region selection, being, you know, very rigorous about what areas and then what sites within those areas that we allow into the study based on historical data and historic ability to execute successful trials. And so that's been really important to us. Second, as Michael mentioned, you know, really rigorous thought around I/E criteria and not making any sacrifices in terms of trying to have an easier I/E criteria to enroll, which potentially wouldn't be as comparable to what we've seen in the past with Dupixent, lebrikizumab, and others. You know, one example of that is making sure that patients are EASI-16 both at screening and baseline. You know, it's just a small example of the way we've thought about that. That's obviously the most difficult criteria to enroll in terms of EASI scores, but we think will lead to the best trial outcomes there. And then I think the final overarching piece too is just really intense oversight of sites. You know, we think this is really important in terms of, you know, not only our relationship with them so they have aligned goals with us, you know, but also making sure that we're always looking for them and us to be aligned with enrolling the right patients at the right sites at the right pace. You know, we have, you know, importantly, a large and very experienced clinical operations team to make sure that we're doing everything on an almost minute-to-minute basis to ensure success for every patient enrolled in the trial. Thanks, Carl. And then on the last point about, you know, how hard it is to generate assets with this profile. You know, we've been at this for, you know, about five years now, you know, close to $1 billion in capital raised. And we took our time very methodically while in stealth before we entered the clinic with our first asset, 777, to not just add YTE onto an antibody, but to create fully optimized antibodies in every sense that are going after validated targets, yes, but with every other improvement that we could discover by testing them head-to-head preclinically to get to the non-obvious fully optimized eventual antibodies that we now have four of in the clinic. You know, I think that that has just continued to prove itself out with our readouts, right? Each has exceeded our expectations. When we look at today's readout, you know, there are other OX40s, for instance, that have YTE or half-life extension technology in the clinic. And those have, you know, netted out in the 30-ish day half-life range, right? We've seen other antibodies with half-life extension not delivered to the same extent that we are seeing for our antibodies, not to mention the improvements that we see in formulation, right? While we're not disclosing the exact concentration of the formulation for 990 today for a number of reasons, including IP and to further protect the moat that we have, right? Amlitelimab itself is at 125, and we're saying that we're above 180, right? When we talk about 777, we're at, you know, significantly 40% higher than E bglyss as well. So in everything that we do, we're not just making half-life extended antibodies. We're making fully optimized antibodies. And people can look in our IP now and see that we ran the experiments preclinically, including, you know, a number of not even primate experiments to get to those. The last piece just on that is, right, we endeavor as well to ensure that we can co-formulate our antibodies together. I think that the co-formulation data that we put out today strengthens the proof of concept data we had released at R&D Day and shows that, you know, not only is it stable, but we can do it at a relatively high concentration as well with similar attributes to the monotherapies. So, you know, we have been very thoughtful about how we've assembled our portfolio, and we've recognized that we've got to live with these antibodies that we take into the clinic. We've made sure that we're moving forward just with the best antibodies that we feel can be made against these targets. Thanks, guys. Really appreciate it. And congrats again. Thank you. Your next question comes from the line of Alex Thompson at Stifel. Please go ahead. Hey, great. Thanks for taking our questions and also congrats on the data. I guess maybe can you talk a little about your confidence in dose selection for the 279 proof of concept? What are the key considerations there? And are the phase II-A data for 777 important for sort of finalizing that dose? And then secondarily, you know, I think it's pretty clear what the pathway for a monotherapy is in atopic derm right now, but could you talk a little bit at a high level about what the path towards approval might look like for a co-formulated combination, particularly if 777 is approved first? Thanks. Thanks, Alex. I'll hand it off to Carl to talk about, you know, our dose selection with the spoiler that we're not going to disclose much about that at this time. Yeah. Thanks, Alex, for the question. I think that, you know, I think the, you know, key piece for us as we think about dose selection for the 279 phase I-B head-to-head versus Dupixent is really making sure that we walk away from that with, you know, a successful outcome, you know, with that being a numerical win over Dupixent in the trial. And to that end, really what we want to do is have adequate target coverage for both molecules or both targets within the study design too. As Michael said, we're not disclosing the exact details of that, but, you know, we're going in that with really the goal of making sure we know that this idea that we're taking forward with orthogonally validated mechanisms, we can have a definitive answer on that. Adequate target coverage of both OX40L and IL-13 is really important in that study as well. And then, you know, with regards to the path to approval for the combo, what is, I think, unique about how we're thinking about our combination approach is that we are, you know, currently in Part B of our ongoing 777 study, optimizing the 777 monotherapy dose. That will give us an advantage then when we think about eventual phase II combination of components design for 279 to know what the optimized dose of 777 is and then, right, optimizing 990 around that. You know, I think that there's significant regulatory precedent, you know, 140-plus different co-formulations that have been approved by the FDA. You know, we're seeing other leaders in AD right now, right, start to do co-formulations. And a number of readouts, you know, from J&J coming up this year, you know, AbbVie and others are now, you know, Lilly recently as well talking about the need for co-formulations and as a combination approach to AD. So, you know, we're excited to be at the forefront of bringing combinations co-formulated to atopic derm and think that there is a clear path that's de-risked by 777 being in the lead. And, you know, the last thing that I'll just hit on there is we sometimes get asked about, you know, wouldn't it be easier if you didn't have to do contribution of components or, you know, do actives? I think that in the future, when you think about, you know, 10 years from now when 777 is out there, you know, hopefully being dosed every three to six months, the backbone therapy for atopic derm, at that point, you know, we think that additional drugs coming to market will need to prove themselves via active comparator studies or, you know, via contribution component studies. So we're excited to do that out of the gate, of course, with ours and putting it to the test starting later this year. Thanks. Congrats again. Your next question comes from the line of Akash Tewari of Jefferies. Please go ahead. Hey, thanks so much. Two on my end on the upcoming data sets from Sanofi and then one on atopic derm for IL-13. So firstly, how's your team framing the upcoming OX40 data in asthma from Sanofi? We internally suspect that efficacy would look more modest than what we've seen with Dupixent in a biomarker-controlled population. Would you consider moving forward with the combo approach even if the Sanofi results aren't statistically significant? Number two, if we look at the Sanofi IL-13 TSLP bispecific, it seems like their strong EASI reduction has been driven by population and baseline differences. So how much utility is there from combining overlapping mechanisms like IL-13 and TSLP versus OX40 when you think about your combination strategy? And then finally, Michael, in the prepared remarks, you mentioned 777 will be hitting IL-13 more potently than lebrikizumab. But at the same time, I think your team's been pretty reticent to predict an efficacy benefit as a monotherapy. So what are your latest thoughts on efficacy expectations for your atopic derm data set that's coming up soon? Thank you. Great. Thanks, Akash. You know, for the amlitelimab asthma data, you know, Carl, do you want to speak to, you know, our bit of prognostication? Yeah. I might, you know, I might take the first two kind of in concert, Akash, because I think there's kind of some overlapping themes there. But on the first one, right, just the, you know, expectations for asthma, you know, I think obviously we're awaiting the Sanofi amlitelimab data as much as everyone else in terms of what they do in asthma. And we'll be responsive to that data overall and what our approach is to. So, you know, monotherapy or 279 combination therapy in the future both could be potential options for us given our pipeline, but really we'll be responsive to that data. I think that one of the areas that we're excited to dig into there, right, is just really the patient population they might be able to have an impact on. We know agents like, you know, Dupixent, as you mentioned, have, you know, really great impact on Type 2 high patients, you know, in asthma measured by eosinophils. I think one of the open questions for us is whether OX40L can have a broader impact, you know, on a non, you know, Type 2 high or eosinophilic phenotype population overall. So we'll be awaiting that data and responsive to it. And then I think similarly, and this is why I'm kind of grouping them in terms of the IL-13 TSLP data from lunsekimig, you know, and our approach for APG777 and APG333, right? I think a question there too is not just maybe depth of response that you could get there, but breadth of impact that you could have as we've seen TSLP have greater impact on, you know, non-eosinophilic phenotype than Duppi and others. So we'll be, you know, thinking about how we do that in our own programs as well. You know, this year for respiratory diseases, we're launching asthma trials in with our monotherapy APG777, and we'll disclose more on our combination plans for APG777 and APG333 at a later time this year. Yep. And then, you know, just to pick back up, you know, we will see we're seeing Sanofi launch a number of different phase IIs with their lunsekimig. So, you know, we will be, of course, responsive to that data as it comes out. And those are studies, you know, which should give definitive answers that, you know, can't be juiced by high phenotypes at baseline, for instance. With the, you know, 777 monotherapy, I think that we have been very clear from the beginning and will continue to reiterate that what we have set as the bar is what market research tells us is the bar for us to have what we feel is the leading drug in atopic derm. That is, you know, physicians, patients, and payers are exceedingly clear to us that if we are able to launch this decade with a drug that is equivalent on efficacy and safety to E bglyss and Dupixent, but transformational on dosing at every three and six months in the maintenance setting, that 90+% of patients will act on that drug. The majority, 2/3 of patients are switching over from standard of care to that drug, and 90% of new starts are starting on that drug. So we are very excited about that profile because that is the bar that market research tells us should be the bar. As you point out, we are testing higher exposures of IL-13 inhibition versus what has been tested historically by lebrikizumab. While there are multiple data points suggesting that could lead to better efficacy, we view that as pure upside and not the base case given how strong of a profile equivalent efficacy and safety is. Your next question comes from the line of Julian Harrison of BTIG. Please go ahead. Hi, good morning. Congratulations on these early results and all the recent progress. I'm wondering if you could talk a little more about your enrichment strategy for the phase I-B of APG279. Any notable differences you would highlight compared to how you approach development for a pure TH2 inhibitor? Thank you. Yeah. No, thanks for the question. I think that, you know, for the phase I-B, you know, we're really thinking about making that as comparable as possible to APG777, our ongoing phase II trial there. I think with atopic dermatitis, you know, we're, you know, in a space where, you know, I guess the disease itself is T2 enriched, but, you know, there's nothing in terms of I/E criteria that we're doing with our monotherapy approach or combination approach, you know, to further enrich that. You know, we know AD is heterogeneous, right? And so you're getting patients that are maybe higher on the T2 spectrum versus have other involvement. IL-13 has been repeatedly shown to be the core driver of atopic dermatitis pathophysiology, but obviously other contributors there as well. I don't think any specific enrichment strategy, although a strategy behind that trial to make it as comparable as possible both to APG777-201, our ongoing phase II trial, as well as others like Dupixent and lebrikizumab's phase III trials. Got it. Thanks. That's helpful. And then another on that phase I-B, I'm wondering, you know, what do you expect to be the most informative data points? You know, is there a go/no-go threshold associated with EASI-75 or IGA you're able to share now? Yeah. You know, when we kind of think about what is meaningful in terms of improvement, you know, when we look at where JAKs are, for instance, compared to Dupixent on EASI-75, right, it's approaching 30 points of improvement. You know, we don't think that 30 points is necessary to have something that's transformational in terms of efficacy, right? As long as the safety is there, you know, we hear pretty consistent feedback that 10 points of differentiation on, you know, EASI-75 or IGA 0/1 would be, you know, as one payer said, you know, guess what? We'll pay for it with a profile like that. And, you know, docs, I think, physicians and patients, excuse me, get very excited when it's in that double-digit range. So that's what we'll be looking for. You know, what's also exciting about the phase I-B and how we design it is we'll be looking at efficacy, you know, at multiple time points, including week 16 and week 24. So we'll have multiple comparators. Okay. Excellent. That's helpful. And then a final one for me. I'm just wondering, in light of prior trials of monotherapy OX40 and OX40 ligand inhibitors, are there any learnings from those prior efforts you're applying to your plan to develop 279? Yeah. You know, we're still learning from some of those prior trials. And, you know, we're excited to see additional data we hope at AAD around some of those prior studies just to, you know, understand, you know, if there's anything that we can glean from, you know, dose selection or patient selection or, you know, geographical distribution and some of the changes that took place between, you know, phase II and phase three studies. You know, I think what is important here is we view OX40 ligand as a very exciting add-on, not as a monotherapy. So, you know, while we will be learning as much as we can and always, you know, exploring how to improve our studies, you know, nothing in particular kind of jumps out that, you know, we would apply to the combination per se just based off of those monotherapy studies. But, of course, we'll continue to be responsive to the data that we see. Okay. Great. Thank you, and congrats again. Your next question comes from the line of David Nierengarten of Wedbush. Your line is now open. Hi. Thanks for taking the question. I had two maybe quick ones. First off, I assume since they weren't recorded, but there weren't any, you know, ADA antibodies or anything like that. And then second, when you think further ahead, is there a scenario where the combination goes ahead of the 777 monotherapy or, you know, you prefer to develop one or the other? I'm just curious how you're planning for different outcomes with the mono versus combo therapy. Thanks. Yeah. Thanks, David. Carl, do you want to speak to the first point? Yeah. You know, in the ADA point, obviously still early in the study as this is an interim readout, but we haven't seen any apparent impact from ADAs on PK curves. And so, you know, feel confident in the profile we're showing moving forward. You know, I think moving forward, you know, we're excited about both drugs, 777 and 279, right? With 777, we're in the middle of this year. We'll learn if we have a potential mega blockbuster in the, you know, atopic derm and broader Type 2 inflammation market. And again, right, equivalent efficacy and safety with improved dosing launching later this decade, you know, give us whatever percent market share, you know, you may, that ends up being a mega blockbuster and kind of the foundational asset for us as a company. What we then, you know, want to always be thinking through is, you know, how can we continue to offer innovative solutions for patients and drugs that, you know, will raise the bar for patients? 279, you know, for us, we feel is the ideal approach of orthogonal mechanisms that could do that. I think part of, you know, how quickly 279 shifts into the front line versus, you know, kind of takes JAK and, you know, later line therapy will depend on just the strength of the 777 data, right? If we end up seeing improved efficacy with 777 mono, then, right, you can imagine that 777 mono could persist well beyond, you know, any pressures that might come in the, you know, mid to late 2030s as we see biosimilars enter and, you know, become that mainstay. So just how we think about, you know, shifting patients and growing that market will depend on partially the 777 data middle of this year and then also the relative strength of 279 relative to 777. Thanks. Your next question comes from the line of Salveen Richter of Goldman Sachs. Please go ahead. Good morning. Thanks for taking my question. You mentioned a numerical win versus Dupixent. Could you just speak to what that might look like with regard to the profile that you're hoping to see in the head-to-head versus Dupixent? And then secondly, with regard to the comparison to JAKs here, just your thoughts on whether that sets the efficacy ceiling or theoretically could be improved upon with one of your assets, assuming, you know, combinations and safety and tolerability holding at higher doses? Yeah. Carl, do you want to speak to that first point? Yeah. Happy to. Right. I think, you know, mentioned a numerical win versus Dupixent, right? I think we see that as, you know, at least 10 percentage points better than what Dupi shows in that study. Again, really based on our discussions with, you know, KOLs and, you know, blinded market research we've conducted. That is really, you know, the bar for a, I would say, a multi-targeted approach, whether combination or otherwise, to be successful in a space is that 10 percentage point, you know, on some key endpoints. Yep. And then, you know, kind of dovetailing that into your second question, right? 10 points is, you know, a significant improvement versus what's out there. Of course, you know, in some of these endpoints, JAKs are doing close to 30 points better than Dupixent. You know, whether or not that 30 points better is kind of maxed out, you know, and limited by the tolerability of JAKs, right? We do know that there is a dose-dependent response. I think TBD, you know, 10+ points, you know, we would be very excited about to have. And we'll see, you know. We hope that we're figuring out along with you is 30 really the bar by having a very safe and effective combination that we can fully explore that safe but broad inhibition of the Type 2 and non-Type 2 pathways. Your next question comes from the line of Richard Wagner of Bank of America. Please go ahead. Hello. Yes. Thank you for taking my question. Richard Wagner, Bank of America for Tim Anderson. As you know, UCB is also taking an orthogonal approach to atopic dermatitis with its bispecifics pairing IL-13 with either IL-22 and IL-17. The company at their earnings commented that they had seen positive phase II-A in atopic dermatitis with the IL-22 combination. I wonder if you could remind us the biological rationale for your particular combination and your confidence in that approach and what would be the advantages compared to the UCB bispecifics and specifically I'm thinking about mechanism of action. And then related, is there a potential for a safety risk from hitting the Type 2 pathway both upstream with OX40 and then downstream with IL-13? Thank you. Yep. Thank you for the questions. You know, so for the, you know, a number of kind of different approaches out there, UCB, of course, you know, from what we understand, you know, from their clinical trials and the comments that they made, they ran a small phase I-B study that included IV dosing only for atopic derm patients. And they have had that data for some time and have not yet disclosed it for their IL-13, 17 combo. And they have an IL-13, 22 trial that's ongoing. And I said that they might share that later this year. Of course, right, we defer to them and we'll keep an eye out for that data. You know, when we think about IV dosing for atopic derm patients and, you know, even if that later on converts to subQ, non-half-life extended, you know, we don't see that as a progression for patients necessarily, right? Kind of a step back in some ways. You know, while we're excited to see additional options being made, you know, we view that as more of a later line option versus a front line therapy where we're focused. You know, when we think about what's really exciting about our approach is, right, many years ago we thought, do we want to do a bispecific? Do we want to do a co-formulation? And, well, how do we get to the best eventual product that can be dosed every three to six months and where we can titrate against each target and where we can get the broadest coverage of these pathways? And that is with the OX40 ligand approach because it hits, it does inhibit IL-17. It also inhibits IL-22. It also inhibits TNF-α, interferon gamma, right? Kind of all the different pieces that people are trying to take piecemeal with some of their bispecific approaches, we're able to get all of that with the broad and safe approach of OX40 ligand inhibition and the deep Type 2 inhibition that 777 offers. And then to your last question, right, safety risk, we wanted to be, you know, as sure as anyone that we were taking a safe drug into the clinic here with the co-formulation. And to do that, we ran very high dose combination tox of the co-formulation in our preclinical studies, you know, up to 150 mg/ kg and saw nothing even at that very high dose in non-human primates over three months. So, you know, continue to be as, you know, safe as we can in advancing this and everything that we've seen to date on that and a very broad body of preclinical evidence and pharmacology, you know, including viral assays which show our differentiation versus JAKs, which we started our R&D Day and just the ongoing incredibly safe profile of these mechanisms as monotherapies from others in the clinic supports our view that this should be a safe and hopefully effective therapy. And that was our final question. Ladies and gentlemen, that concludes today's call. Thank you, everyone, for joining. You may now disconnect.