Apogee Therapeutics, Inc. ($APGE)

Good morning, and welcome to the Apogee Therapeutics conference call. [Operator Instructions] Please be advised that this call is being recorded at the company's request. I will now turn the call over to Noel Kurdi, Vice President of Investor Relations at Apogee. Noel, you may begin.

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, CEO, Michael Henderson, will begin the call with an introduction to today's results and the opportunity in atopic dermatitis. Then, Chief Medical Officer, Carl Dambkowski, will walk us through the APEX Part A 52-week maintenance results of zumilokibart in patients with moderate to severe atopic dermatitis. Dr. Ruth Ann Vleugels, of Brigham and Women's Hospital and Harvard Medical School, will then share an update on the unmet need in atopic dermatitis, followed by an overview of our zumilokibart development program by Kristine Nograles, Apogee's Head of Clinical Development and Medical Affairs. Before moving on to the Q&A, Michael will summarize our vision for building a leading I&I company and our anticipated milestones through the end of the year. The subsequent Q&A will be led by Michael; Carl; Apogee's CFO, Jane Pritchett Henderson; Chief Commercial Officer, Jeff Hartness; and Dr. Vleugels. I will now turn the call over to Michael.

Thanks, Noel, and thank you all for your time today. We founded Apogee with the goal to transform standard of care for atopic derm and Type 2 inflammation. Atopic derm is the fastest-growing I&I market and could soon become the largest, projected to reach over $50 billion. Yet treatment options are limited, and even modestly differentiated products are quickly becoming blockbusters in this market. Today we are excited to share data demonstrating the potential for zumilokibart, or zumi, to deliver a transformative treatment for atopic derm patients with quarterly or semiannual dosing, potentially the first every-6-month-dose drug in dermatology. In addition to dosing, our fully optimized IL-13 antibody is driving rapid itch and lesion response that shows profound deepening over time with both 3 and 6-month dosing. This contrasts with DUPIXENT, which has not demonstrated deepening beyond week 16. We are thankful to the patients and physicians that have enabled us to share this with you today. Diving into the data, zumi demonstrated 75% maintenance of EASI-75 response and 86% maintenance of IGA 0/1 response with every-3-month dosing. Every-6-month dosing demonstrated 85% maintenance of EASI-75 response and 78% maintenance of IGA 0/1. After induction, all zumi patients were randomized to maintenance. So in addition to assessing maintenance of response, we were also able to assess the efficacy for zumi patients that were treated for up to the full 52 weeks. Unlike the standard of care, which has not demonstrated a deepening of response after week 16, we observed deepening across every lesional and itch endpoint we tested. On the safety front, zumi demonstrated a well-tolerated profile generally consistent with the class. Taken together, we believe these data highlight IL-13 inhibition as the ideal mechanism for the treatment of atopic derm and support us taking zumi forward with both every 3 and 6-month dosing. Our Phase IIIs are on track to initiate in the second half of this year. We have a unique opportunity with zumi to potentially transform the future $50 billion atopic derm market. After showing last year that 2/3 of patients treated with zumi achieved an EASI-75 response by week 16, our data today demonstrate that zumi can be dosed as infrequently as every 6 months in maintenance and drive deeper responses for patients. Overall, the APEX Part A data affirm our belief that we can deliver a potentially best-in-class treatment for atopic derm that improves our standard of care across both dosing and efficacy. The white space between us and other investigational and approved treatments here speaks for itself. I'll now hand the call over to our Chief Medical Officer, Dr. Carl Dambkowski, to walk us through today's data in more detail.

Thanks, Michael. I'm honored to share these exciting results with you all today. The results we will share today are from the maintenance portion of the Phase II APEX Part A study. In this double-blind, treatment-masked portion of the study, patients that received zumilokibart during induction were re-randomized to every 3 and 6-month maintenance dosing regimens. Additionally, patients on placebo during the first 16 weeks of the study were transitioned to a zumilokibart dosing regimen similar to the induction period. The study design replicates the upadacitinib Phase III trials and allowed us to carry out 3 distinct efficacy analyses. We first assessed maintenance of response among patients randomized to zumilokibart in induction who achieved an EASI-75 or IGA 0/1 response at week 16. We also assessed efficacy across the full 52-week treatment period for all patients randomized to zumilokibart at induction, including patients that did not achieve a response at week 16. This population is more akin to how physicians think about their patients over time and allows us to understand whether or not responses plateau. Finally, we assessed efficacy for patients randomized to placebo in induction that crossed over to zumilokibart in maintenance. Baseline characteristics and demographics of the patients for the population receiving at least 1 dose of zumilokibart were in line with expectations and consistent with what was observed for the entire randomized population. Zumilokibart was well tolerated over 52 weeks of treatment, showing a safety profile generally consistent with the 16-week induction period and in line with expectations for the IL-13 class. Adverse events that occurred in 5% or more of patients included non-infective conjunctivitis, upper respiratory tract infection, nasopharyngitis and dermatitis atopic. When conjunctivitis cases were pooled across all preferred terms, we saw a 20.2% rate with less than 1% discontinuations across the full 52-week treatment period, generally in line with the class. We did not observe any impact of ADAs on PK, efficacy or safety. The pooled rate of conjunctivitis for zumilokibart is comparable to dupilumab and lebrikizumab, which saw rates of approximately 14% to 30% across 52 weeks of treatment for patients with atopic dermatitis. Now turning to the efficacy results. We will first review maintenance of response data. This data represents how well patients were able to maintain a response once achieved. This section will focus on patients who achieved either an EASI-75 or IGA 0/1 response at week 16 and received at least 1 dose of zumilokibart during maintenance. Starting with EASI-75, zumilokibart demonstrated an 85% maintenance of response with every-6-month dosing and a 75% maintenance of response with every-3-month dosing at week 52. These results compare favorably with the standard of care, which is dosed every 2 to 4 weeks. The non-head-to-head trial comparison is shown to the right. Moving to IGA 0/1. Zumilokibart demonstrated a 78% maintenance of response with every-6-month dosing and an 86% maintenance of response with every-3-month dosing at week 52. As with EASI-75 maintenance of response, these results compare favorably with the standard of care. Again, the non head-to-head trial comparison is shown to the right. Among week 16 EASI-75 responders, patients on zumilokibart showed stable and deep improvements in EASI and itch through end of study for both every 3 and 6-month dosing regimens. Specifically, for percent change from baseline in EASI at week 52, zumilokibart demonstrated a reduction of 88% with every-6-month dosing and 82% with every-3-month dosing. For percent change from baseline in itch NRS at week 48, zumilokibart demonstrated a reduction of 67% with every-6-month dosing and 77% with every-3-month dosing. Now we will look across efficacy for the entire 52-week period for all patients treated with zumilokibart starting in induction. This data represents how well a patient does over time, which is more representative of how physicians think about patient treatment. An important aspect of our trial design is that all patients, regardless of responder status at week 16, were re-randomized in a blinded fashion to every 3 or 6-month dosing. This allows us to see how all patients respond to zumilokibart treatment over the course of a year, which is an important consideration in a physician's treatment decision. The trial design and analysis methodology are similar to the upadacitinib Phase III trials, but differ from how dupilumab and lebrikizumab conducted their studies where only responding patients continued on treatment in a blinded fashion. We believe that mechanism is important in terms of optimal responses for patients with moderate to severe atopic dermatitis. IL-13 has repeatedly been shown to be the key cytokine driving atopic dermatitis. Drugs targeting IL-4 receptor alpha are able to block IL-13 action, but do not change the underlying amount of IL-13. With dupilumab, this has potentially led to a plateau in response, as shown on their FDA label where IGA 0/1 was 39% at week 16 and 36% at week 52 in a study conducted of dupilumab in combination with topical corticosteroids. In contrast, zumilokibart blocks the action of IL-13 at the receptor level, in addition to neutralizing IL-13. Mechanism and optimized exposures of zumilokibart led to a greater than 99% inhibition of IL-13, potentially allowing for continued improvement over time as continued IL-13 neutralization allows the underlying inflammatory milieu in the skin to normalize. For zumilokibart, both through targeting IL-13 and optimizing exposures, we see an IGA 0/1 response of 37% at week 16, improving to 52% for every-6-month dosing and 72% for every-3-month dosing at week 52. Further, we saw for both every 3 and 6-month dosing, response deepened in all lesional and itch endpoints tested, which we will discuss further now. Across the full treatment population, zumilokibart demonstrated an IGA 0/1 of 52% and 72% at week 52 for every-3 and every-6-month dosing, respectively, an increase of 14 and 35 percentage points from week 16. A comparison of response rates at week 52 to standard of care in non-head-to-head trials is shown to the right. As mentioned earlier, the trial design is similar to upadacitinib Phase III studies for which we provided comparisons. Unfortunately, no comparable monotherapy data is available for dupilumab and lebrikizumab to provide a comparative point. On itch, zumilokibart demonstrated reductions from baseline of 64% and 73% for every 6 and 3-month dosing, respectively, at week 52, an improvement of 13 and 22 percentage points from week 16. On EASI-75, zumilokibart demonstrated a response rate of 81% and 88% at week 52 for every 6 and 3-month dosing, respectively, an increase of 6 and 13 percentage points from week 16. Consistent with our IGA 0/1 results, zumilokibart demonstrated an EASI-90 of 48% and 75% for every 6 and 3-month dosing, respectively, at week 52, an increase of 10 and 36 percentage points from week 16. On EASI-100, which indicates patients have clear skin, zumilokibart demonstrated a response rate of 19% and 41% for every 6 and 3-month dosing, respectively, at week 52, an increase of 11 and 33 percentage points from week 16. We are encouraged by the results presented today and look forward to further evaluation of zumilokibart. Dr. Kristine Nograles, our Head of Clinical Development and Medical Affairs, will provide an update on what is next for the program a bit later in the call. But first, Dr. Ruth Ann Vleugels will walk us through the unmet need in atopic dermatitis and where she sees zumilokibart fitting in to the treatment paradigm. Dr. Vleugels is the Heidi and Scott Schuster Distinguished Chair of Dermatology and the Director of the Atopic Dermatitis Program at Brigham and Women's Hospital and a Professor of Dermatology at Harvard Medical School. Thank you for joining us today, Dr. Vleugels.

Thank you so much for that kind introduction, Carl. I really appreciate it. It's really been an honor for me to care for patients with atopic dermatitis over the past 2 decades. And that's primarily because of the prominent quality-of-life impact on these patients. We really consider atopic dermatitis to be a severe and systemic disease. And to kind of level-set on the impact on their quality of life, I want you to actually look at these 2 patients and think about the impact of not only the visible rash, but also the profound and debilitating itch that accompanies it. And in fact, when I'm teaching students at Harvard Medical School, I'll often try to teach them this via an example. And I'll say, imagine you had a couple of hundred mosquito bites, or that you had poison ivy but it was over a substantial part of your skin. And really think about how challenging that would be if not only it lasted for a week or 2, but in fact, for years. Because this is a chronic inflammatory illness and patients deal with this day in and day out for years. And so if we think about that personal quality of life, what does the data show us? So we actually have robust data regarding this quality-of-life impact, both in children and in adults. So when I'm seeing kids at Boston Children's Hospital, I know that based on data, these kids lose a substantial amount of sleep because of their disease. And that loss of sleep not only impacts the kids, it actually impacts their parents, caregivers, families as well. In addition, these children lose days of school because of their atopic dermatitis. And in fact, we know that their atopic dermatitis has an ability to impact their growth. So we see growth restriction as well, which really is very unfortunate. In our adult patients, many of these themes carry over. We see a higher propensity to mood disorders, including depression in patients with atopic dermatitis. We also know that our patients lose days of work because of their skin condition. And not only do they have reduced physical activity, but they have more challenges in social relationships as well. So because atopic dermatitis is actually our most common inflammatory skin disease, this overall quality-of-life impact really impacts our health care system as well. Not only do we need a high volume of consultations, but many of these patients are hospitalized because of their atopic dermatitis. And overall, there is really a high annual cost burden related specifically to atopic dermatitis. So thankfully, we have moved the needle in the last decade in terms of the care of our patients with atopic dermatitis. And to really think about this, I want to remind you what traditionally was used for atopic dermatitis prior to 2017. And that was primarily systemic corticosteroids and topical therapies, including topical corticosteroids. And both of these buckets of medications do have limitations. So first, systemic steroids have substantial side effects. We know they can result in bone loss, they can result in diabetes, high blood pressure and many other side effects. And in fact, the American Academy of Dermatology recommends against their use in atopic dermatitis. Topical corticosteroids can help with individual lesions, but they don't actually improve the overall inflammatory burden of atopic dermatitis. And actually, we often think of topical therapies as more of a band-aid, because although they can improve individual lesions, they can't actually prevent new lesions from coming. And I think that's a really important point. So as you can see here, however, since 2017, we have had the approval of 4 biologic therapies and 2 oral small molecule JAK inhibitors specifically for atopic dermatitis. So now if we think about these therapies specifically, we have had improvement in the care of our patients with atopic dermatitis. Both dupilumab and lebrikizumab are in the IL-4, IL-13 family, and these medicines do show significant lesion benefit; however, they do have to be dosed by self-injection every 2 to 4 weeks. We also have nemolizumab, which is an anti-IL-31 therapy. This particularly impacts the itch associated with atopic dermatitis, but there's limited improvement in rash and this medication still needs to be dosed every 4 weeks. Our JAK inhibitors are dosed once a day, they're oral therapies. And they do have rapid onset of action both for rash and itch. However, they do both carry a boxed warning for blood clots, major cardiac events and cancers. And these boxed warnings have impacted the practicality of prescriptions for these medications for atopic dermatitis globally. So in this broad clinical context, how do I think that zumilokibart could address some of these unmet needs in atopic dermatitis? Well, first and foremost, we really need more therapies for atopic dermatitis that are not only safe and effective, but also have the ability to reduce the injection burden. And we know that the frequency of injecting biologic medications is actually extremely important to our patients. We have deep experience with this from our psoriasis patients over the last 15 years. So something that's really important to me as an atopic dermatitist is the fact that zumilokibart demonstrated not only a strong clinical response at week 16, but also that these responses were maintained with every-3-month and every-6-month dosing. Because again, I really know that dosing frequency matters to my patients. In addition, something that is important to me is that there were deep responses on both skin and itch in a substantial portion of patients by week 52. And this even was on the EASI-100, and of course, that EASI-100 represents completely clear skin. So that's an endpoint we really could barely dream of several years ago in atopic dermatitis. So we know in our atopic dermatitis program that both physicians and patients really have safety driving their decision-making. And so I think this is imperative that zumilokibart was well tolerated across both dosing regimens with a safety profile that's really in line with the IL-4 and IL-13 class. And this is important because my dermatology colleagues really favor the IL-4 and 13 class given its safety profile overall. And so in sum, zumilokibart has the potential to improve the care of patients with atopic dermatitis, not only by providing long-term disease control, but also having the ability to be dosed with 2 to 4 maintenance injections per year, which again we know to be highly meaningful for our patients. Thank you so much for your interest in the care of our patients with atopic dermatitis.

Thank you, Dr. Vleugels, for walking us through the key unmet needs in atopic dermatitis and where zumilokibart could potentially fit into the future treatment paradigm. Our Phase II APEX trial was designed as a 2-part study incorporating both proof of concept and dose optimization components. Today we shared 52-week results from Part A, the proof of concept portion of the study. Part B is the placebo-controlled dose-optimization portion of the study where patients are randomized equally to either high, mid or low-dose zumilokibart versus placebo. For the high dose in Part B, we are testing higher induction exposures compared to Part A, which is modeled to have about 90% to 100% greater exposure than Ebglyss. Given the excitement around the study overall, we were able to increase the number of participants in Part B and complete enrollment ahead of schedule. We remain on track to share the Part B 16-week results in Q2 of 2026, which we expect to enable Phase III dose selection and trial initiation later this year, supporting the planned launch of zumilokibart in AD in 2029, if approved. As we think about the broad potential for zumi in I&I, we are well on our way to realizing zumi's pipeline and a product potential in multiple blockbuster expansions, starting with asthma and eosinophilic esophagitis. In fact, we've already begun to see zumi's potential beyond AD with positive Phase Ib asthma data disclosed earlier this year, where treatment with zumi led to deep and sustained suppression of FeNO, a key asthma biomarker. We remain on track to provide an update later this year on our plans for the ASPIRE asthma and ELEVATE eosinophilic esophagitis trials. Beyond these 3 initial indications, zumi has potential in multiple other dermatology, respiratory and GI indications where we have the option for a straight-to-Phase-III approach, leveraging optimized Phase IIb dose regimens for each therapeutic area. I will now pass the call over to Michael for closing remarks.

Thank you, Kristine. When we consider the profile of an atopic derm treatment that will truly be transformative to patients, we look at lesion control, itch relief and dosing. These are the areas that patients and physicians tell us are in most need of innovation, where current biologics come up short. Based on today's results, we are confident in zumi's potential to be the next clearly differentiated first-line product to launch in atopic dermatitis. Zumi demonstrated strong maintenance of response for both every 3 and 6-month maintenance dosing, confirming the potential for greatly reduced injection burden. As few as 2 to 4 maintenance dosing days per year compared to 26 dosing days for standard of care. Zumi has the potential to be the first 6-month dosed dermatology drug, a breakthrough for patients. Zumi previously demonstrated rapid itch relief at 48 hours, and today's data demonstrated the further potential for deepening of responses through 52 weeks across all lesion and itch endpoints tested. Atopic derm is the largest and fastest-growing I&I market. DUPIXENT's launch in atopic derma alone has outpaced the entire $25 billion plaque psoriasis biologics market combined. Atopic derm remains significantly underpenetrated, and new entrants with limited differentiation are quickly becoming blockbusters, while DUPIXENT continues to build towards an estimated $30 billion in peak sales across all indications, speaking to the unmet need and desire for new options. Zumi's planned launch in 2029 could be the next meaningful frontline drug launch for this population. Today's data demonstrates zumi's potential to transform standard of care in atopic derm and establish Apogee as a leader in this massive market. To recap, in just 3 short months, 2026 has already been a strong year for Apogee, beginning with our Phase Ib asthma readout, a derisking proof-of-concept moment for zumi and respiratory conditions, followed by today's APEX Part A data showcasing zumi's potential for transformative dosing and efficacy. We look forward to another APEX readout anticipated next quarter with our Part B dose optimization data. This 16-week data will allow us to select the induction dose for Phase III, a key step prior to initiating the first of our expected Phase III studies in atopic derm later this year. Also, in the second half of the year, we plan to share 24-week data for APG279 from a head-to-head trial with dupi, and is now fully enrolled. We look forward to the exciting months ahead as we seek to deliver potentially best-in-class medicines across a wide range of I&I conditions of high unmet need. I will now hand the call back over to the operator to begin Q&A. Thank you.

[Operator Instructions] And our first question comes from Seamus Fernandez from Guggenheim.

Great. So just -- I'm going to limit to one question here. But can you help us understand, beyond just the strategy for Phase III, what you actually see as the appropriate dose for starting and continuing maintenance on the basis of Part A? And then hope -- what you hope to achieve with Part B. Is it just deeper responses earlier, so the kinetics of response? Or is it perhaps even a better outcome versus that comparison?

Seamus, appreciate the question. Yes. So we're obviously very happy with the results here. And it's clear to us and kind of the physicians that we've shared this with, that moving into Phase III, with an eye towards '29 approval, right, we want to give patients and physicians the option to have a 3 and 6-month dose. And we saw really nice maintenance response for both. And we were surprised at the level of deepening that we saw for both of them, which again, right, has not been kind of seen with standard of care, and we think there was a mechanistic rationale there. So as we think through what that means for Phase III, we will have a single induction dose, that will be informed by our Part B that comes next quarter. We will see if higher exposures with the top dose lead to us getting to better efficacy faster. And that's really, to your point, the kinetics of response, right? Are we going to see that higher dose getting to faster efficacy? But we're seeing better efficacy over time with the Part A dose, which is the mid dose. And then that will give us the induction dose. And then from all the data that we saw here and additional data that we're gathering from the long-term extension, et cetera, we will be able to go into the Phase III with a 3 and 6-month dose with the aim of not having docs have to choose between efficacy and dosing, but offering them both options, which we now are in a position to go forward with it with a lot of confidence on.

Our next question comes from Tyler Van Buren from TD Cowen.

Congrats on the very exciting data. Maybe I'll ask a question to Dr. Vleugels. Thanks for your time. Can you elaborate on how you would incorporate zumi into your practice? And specifically discuss the percentage of treatment-naive and treatment-experienced patients you think about using zumi in? And maybe just a comment on safety as well with a focus on conjunctivitis in particular.

All right. Thanks for the great questions, very important clinical questions. So for the first question, I would just comment first of all that I would give this agent to essentially all treatment-naive patients if it were available today. But I want to highlight why that is. Essentially because this has the safety of a biologic, which is essentially going to be first line for any of my colleague dermatologists who prescribe for atopic dermatitis. But also the key points here is we have more rapid itch relief than our other biologics that are traditionally used as first line. The deepening is very important to me because those deepening responses are comparable to the higher dose of upadacitinib, which is our more effective JAK inhibitor, at 52 weeks, and that's very impressive. And we have many, many fewer doses. So if I put all of those things together, that's like a huge win for the atopic dermatitis community. And so treatment-naive patients would be offered this first, I'd say, by the vast majority of prescribers. And then the second part of that is who would transition to this. And so given those same principles I just mentioned and the fact that the delta of doses is large, right, so we're going from 13 to 26 doses a year to 2 to 4 doses a year, we know from our experience with psoriasis, right, when -- back when I started practicing, the only agents we had were dosed every 2 weeks and then they evolved to now being more like 2 to 3 months, that the vast majority of patients, if you can get that wide of a delta, will want to switch therapies, as long as we think they're equally even effective. So I would say, in my practice, usually about 80% of patients will transition as long as the delta of injection frequency is substantial enough, which it is here. And we have the additional benefits I already outlined. I think your second question was about side effects. So I sort of would joke here because I'm an autoimmune disease expert, and so I always love it when the safety profile of a drug I get to talk about is so clean that I just talk about conjunctivitis. And I just want to kind of give you a perspective of how I talk to my patients about this in clinic. So if I'm going to prescribe a medication that's in this family, so sort of in the IL-4, IL-13 family, I'm telling my patients, okay, the number one side effect we see from this is that, occasionally, patients will get red eye that's not related to an infection. And we know that red eyes can actually just happen in atopic dermatitis at baseline, but occasionally, this can happen and it's related to the medication. The good news is that fewer than 1% of patients that get this have to stop the medication. That's extremely rare. And in fact, when patients do get this, usually, we don't have to intervene in any way or we can use over-the-counter drops. Like that's my safety counseling. So that's very, very simple. And we know this to be the case because, what we just heard from the Apogee team, this is why other therapies in this class are so widely prescribed, because this is not a safety concern for dermatologists. I think the second point is that the type of conjunctivitis to focus on when you're thinking about a true side effect is only the non-infective conjunctivitis, because other forms wouldn't be related to drug. And even in non-infective conjunctivitis, some will just be because the patients have baseline atopic dermatitis regardless. And as I mentioned, the conjunctivitis, if it comes, is easily managed. And I would view this as completely in line with the class, and so it wouldn't be a driving factor in the prescribing habits of my colleagues. And this is completely what I would expect for this class and easy to manage with patients.

Our next question comes from Patrick Culliton from Stifel.

This is actually Alex Thompson from Stifel. I appreciate the question and thanks for keeping us on the call here. I have a follow-up on the conjunctivitis commentary. Wondering if you could provide a little bit more color on sort of the duration of conjunctivitis relative to what you saw in the 16-week portion, and if there's any trends relative to exposure, et cetera, as you look to the maintenance dosing?

Alex, I thought we were going to get to meet your brother there for a moment. I'll hand it off to Carl to kind of speak to what we saw with duration, et cetera.

Yes, Alex. I think what we saw here is very consistent with what we disclosed during the Part A induction readout. In terms of duration, what we saw for median duration of conjunctivitis across the whole 52-week period was less than a month. So just 27.5 days was the median duration, very short-lived overall. And over 85% of cases resolved within 90 days. So we're seeing that these are generally short-lived and don't seem to necessarily be related to the long half-life we have here overall, which we know was a question coming into the study overall. Second, I think great question on trends in exposure. And this is again similar answer to what we had with the Part A induction data, which, as we've looked at it, we see absolutely no trends between or no relationship between exposure and conjunctivitis. And that's on a couple of fronts. One, that is on just the rate itself. So your likelihood to get conjunctivitis has no relation to exposure. And then second is on duration as well. So the duration of patients' conjunctivitis is also unrelated to their exposure too. So overall, I would say, as we've heard here, very in line with the class, short-lived overall and very manageable and does not seem to be related to exposures.

Our next question comes from Akash Tewari from Jefferies.

This is Phoebe on for Akash. Given today's data, how has your bar for success changed for the upcoming readout for the combo with OX40 versus DUPIXENT, which was previously about 8% to 10% benefit? And then how has your confidence changed on the Part B higher exposure that is upcoming in Q2? And then just lastly, were there any patients that didn't move from induction to maintenance, it kind of seems like there should be a little bit higher number of patients for the n? So just want to get any clarity there.

Yes, Phoebe. So clearly, we're still digesting the data. We did not expect to see kind of deepening to this degree for both the 3 and 6-month dose, again, right, given that we know DUPIXENT from their studies just did not demonstrate deepening. So a pleasant surprise. As we think about Part B, that will tell us, do we get to better efficacy faster with a higher exposure? So again, really the kinetics of it, right? We're seeing really provocative biomarker data, which Dr. Guttman will be sharing at upcoming conferences. I mean we obviously have AAD, the late-breaker, coming up on the basis of these results, and also some additional conferences like SID, where we're seeing not just Type 2 inflammation come down, but also Type 1 and 3 inflammation. So it seems if you do hit IL-13 kind of hard in the beginning, like we are, that you're not just kind of -- you really are hitting the disease at its source and you're bringing down a variety of different inflammatory types, which I think really is showing IL-13 is the driver. So again, a higher exposure can help us to get to take out that driver faster and get to better responses. That would be great. Whether or not it happens by week 16, we'll find out with the Part B data. Either as a win in our view. And then we've said all along, we think our combo IL-13 and OX40 ligand fixed-dose co-formation could be the second-line drug of choice in atopic derm. We will be able to see that data, it is now fully enrolled, so the cake is baked, we'll get that by the end of this year. And we'll be able to compare: is OX40L adding to what zumi is doing over -- within the first 24 weeks? If so, then it could still be the second-line drug of choice. But all along, right, we've said that if -- the better that zumi looks, right, the higher the bar for combo will go, which is ultimately a win for patients kind of regardless of how we cut it. So we just need more data to decide. But I'll hand it off to Carl for the second question.

Yes. So thanks for the question, Phoebe, on kind of the rollover rate overall. What we saw in -- from induction to maintenance is about 10% of patients don't move from induction to maintenance. This is very in line, if not on the lower side, of what we see in studies. And the reason patients aren't rolling over are wide, I guess, in the things that happened. For example, we had 1 patient who was a responder that got pregnant and, therefore, discontinued study due to that. We've had patients move out of the country, et cetera. So the discontinuation rate is really, from induction to maintenance, is really due to, I guess, life circumstances more than drug related. And then the maintenance section of the study too, we had about a 10% dropout rate too, again, on the lower side of what we've seen for trials, this. And again, the reasons are, I would call them, more life events than anything drug related. So a very strong continuation rate from first dose to end of study and gives us more confidence in the data we're seeing here overall.

Our next question comes from Michael Yee from UBS.

Congrats on the data. A quick one for management. So on conjunctivitis, we saw 4 new cases of non-infective conjunctivitis. Could you please give us more color on which arms where these new conjunctivitis cases observed? Were they observed in the maintenance arms or primarily in patients who switched from placebo to the active drug arm?

Yes. The primary driver of the new cases is in those patients that went from placebo to drug, as would be expected. And what we've seen is very similar rates across the different arms in terms of placebo crossover versus Q-12 versus Q-24. So I think what we're seeing is really a class effect here and does not seem to be related to exposure overall.

Our next question comes from Julian Harrison from BTIG.

Congratulations on these results. First, I'm wondering if you could talk about how zumi's efficacy and convenience profile maybe can expand the injectable category for atopic dermatitis? Would you expect maybe lower injection burden to maybe help facilitate the transition from topicals? And then, Dr. Vleugels, I'd love to get your reaction on how these data compared to RINVOQ and JAK inhibitors broadly. Was that in line with your expectations ahead of data? And would you maybe expect progressive deepening responses beyond 52 weeks just based on the trends we've seen so far?

Julian, I'll start, then I'll hand it off to Dr. Vleugels. So I think historically, when we look at markets where longer-acting, better-dose drugs have entered, right, psoriasis being kind of the clearest example that we can call from given the shared dermatology presence, you see a pretty strong uptick in terms of TRx and NBRx, kind of however you cut it, when you get that -- especially, right, what we've seen, quarterly-dosed drug. We don't know what a biannual, right, twice-a-year dosed drug will do in derm because we hope to be the first now to launch within every-6-month dose drug. So excited to chart new waters there, but you do historically just see a pretty strong uptick in scripts. And our own market research data has shown a very strong willingness for patients that are currently just on topical corticosteroids to switch and take on a biologic, if it is dosed with our sort of profile, whereas historically, those same patients are not willing to do it for an every 2 to 4-week dosed drug. But I'll let Dr. Vleugels comment further.

Yes. I'd love to chime in on this question because this is something I literally deal with every single day in clinic. So the frequency of dosing really matters to get the -- over the activation energy, right? So in other words, not only is it that they're more willing to start, for example, in psoriasis when we say we have every 3 months and we say, "You can inject this 4 times a year and we can get you clear," right? That's a huge motivator for patients. But also the number one reason people come off their atopic dermatitis systemic therapies is because of the frequency of injections, right? So they get sick of injecting every 2 weeks, and so you actually lose people for that reason. So it's kind of both ways. It's easier to get them over the hump, but it's also easier to maintain their disease control because they don't want to give up on their injections. I think both of those are really important from a clinical context. I think your second question is really a perfect one because I've been very excited about this therapy since I knew it was coming, like very excited. And the reason for that is, even though as an autoimmune expert I'm very comfortable with prescribing JAK inhibitors for a variety of indications, most of my colleagues are absolutely not comfortable with that. So we have really needed in dermatology a therapy that can move the needle in terms of what we would always call like JAK-like efficacy, but the safety of a biologic. Like that has been what we've been looking for as experts in atopic dermatitis. And so I've been very excited about this agent. But this 52-week data is outstanding, right? So the fact that the EASI-75 and EASI-100 data is in line not only with a JAK inhibitor, but the higher dose of the more effective JAK inhibitor, is really very impressive. And I think that will be very meaningful for my dermatology colleagues because this is sort of the combination that we've been looking for, sort of that increased efficacy in -- with the safety of a biologic therapy.

Our next question comes from Geoff Meacham from Citi.

This is Nishant on for Geoff. So for the management, will you disclose the week 12 and week 24 trough concentrations versus the therapeutic threshold? And how many patients, if any, fell beyond the threshold? Just trying to check if there's any correlation between trough levels and efficacy waning. And for Dr. Vleugels, in terms of patient-reported outcomes, like itch, sleep or like work productivity or treatment burden, which of these outcomes do you think most convincingly show real-world value and support adoption of 6-month kind of treatment option for this disease?

Great. Nishant, I'll hand it up to Carl to kind of speak to our exposures, and then we'll go to Dr. Vleugels.

Yes. So what we saw in terms of our exposures, we had previously disclosed our modeling exposures after our Phase I data. But the great thing is that in patients with atopic dermatitis in general, other patients too with asthma that we've seen, the actual exposures that we're seeing really match the modeled exposures extremely well. So this is a really well-behaved antibody, which is nice to see overall. In terms of our Q-12 week C trough, the value is just above what that of lebrikizumab Q-4 weeks is based on their model exposures too. So a little more overall than what they have. But in that first year of treatment, because of the induction regimen as well as the Q-12 week dosing, we do give on an AUC basis a decent amount more exposure compared to lebrikizumab. In terms of Q-24 week dosing, our C trough is a little below what lebrikizumab's is. But again, over that first year of treatment, slightly higher exposures on an AUC basis than what lebrikizumab has. And so we think that's driving part of the results that we're seeing, especially on the deepening of response overall. And then finally, in terms of, I think, your question related to what we see in terms of exposures versus the efficacy we're seeing, I think that the deepening, especially, I think, on maintenance of response, we look at this and say, Q-3 months and Q-6 months, both maintain responses extremely well. I think very little difference between the 2 dose regimens there. But on deepening of response, it does seem to be what is driving the better efficacy for Q-3 months versus Q-6 months, both of which show deepening. So I think that's important, both of these are showing deepening, but a little more deepening with Q-3 months. And obviously, as we digest this data and plan for Phase III launches later this year, we'll take that into account to make sure we're really optimizing benefits for patients. Now I'll turn to Dr. Vleugels in terms of your second question was related to what outcome for patients is maybe most meaningful in driving value here.

Thanks, Carl. So I -- it's interesting because I do think that most patients would align that itch is what really drives their quality of life because it impacts so many of the facets that I spoke about in the video. And I think something very important though is where we're moving for atopic dermatitis is you have to have both lesion clearance and itch control, right? These are the 2 together that you want. So we have some therapies, for example, like nemolizumab, that does well for itch but it's not so great for lesion control. And that's just not where we're going in this disease. You need both. And that's actually why the comparison to the upadacitinib-lebo ob study is important, because, of course, they were able to look at itch and lesion control. And so here, what's important to me is that we're getting both of those, right? And so we're getting itch, and it's more rapid than the other IL-4/13 in the class, and it's sustained and deepened. And the same, sustained and deepened for the lesion control. I think that's really why, again, that I'm excited about what this will do for our patients with atopic dermatitis.

Our next question comes from David Nierengarten from Wedbush Securities.

Maybe one for Jeff on the commercial side. How are you planning eventual launch activities? Are you really planning to go for frontline patients, treatment-naive patients or post-dupi patients, all of the above? And how might that differ in terms of spend in sales force?

Yes, David. I think, first and foremost, this is a frontline agent. We've said that from the beginning. I think these data really strengthen that position. And by first-line agent, what I mean is we have the ability for biologic-naive patients to move over. I think you heard from Dr. Vleugels how important it is to be able to get these biologic-naive patients over into biologics versus on topicals. And the number one reason that patients will not move over is because it's dosed every 2 to 4 weeks, these injections. So as we talk to patients, and market research shows that patients are 3x more likely to start on a quarterly dosed product or better than the current products in the market. That's the largest opportunity that we see from a script and revenue perspective. But we also know that, as Dr. Vleugels pointed out, you're going to have a lot of patients that are currently on biologics that want that deepening of efficacy and they want that every 3 or 6-month dosing. And in this particular case, if you look at our patients in this study, that our 16-week responders, over half of them get to EASI-100 complete clearance in the first year. That truly is life-changing for these patients. So I will tell you that we will be building our share by both increasing biologic penetration as well as patients looking to switch. In terms of your second question around our planned launch and how we will go about this and the cost of that, we're really fortunate in launching in AD first because this is a very targeted space. If you look at the 2 most recent launches with Ebglyss and Nemluvio, both of which are on track to become blockbusters this year, both of which launched with less than 150 sales professionals. So this is a very targeted space that we feel confident that we can go out build share quickly and be able to really drive biologic penetration and change the way this disease state is managed.

Our next question comes from David Hoang from Deutsche Bank.

So maybe one for the KOL, Dr. Vleugels. We have some data out now on some novel oral therapies targeting STAT6 and ITK, just to name a few. If more novel orals become available in the treatment paradigm, how might you and your patients weigh the option of a long-acting injectable biologic versus an oral therapy?

Thanks for that clinical question, I really appreciate it. So a couple of things I may want to mention kind of leading into the specific oral therapy you mentioned. The first is atopic dermatitis currently is a purely biologic market in dermatology, right? So in other words, people are not prescribing old-school DMARDs, which are oral, and they're rarely prescribing a JAK inhibitor. They're usually using it like only after they've cycled through biologics or in unique expertise situations. And so the reason why I mentioned this is dermatologists are very, very comfortable prescribing biologics. And in particular, they're very comfortable using the IL-4, IL-13 family as first line, right? So I think that's just like to level-set. And then second, we have a daily oral therapy, which is the JAK inhibition, which of course has the box warning, which limits its prescriptions. But the key compared to some of the other fields you may study is dermatologists, as I mentioned earlier, are primarily driven by safety. This is a field where people do not have internal medicine background, they have a year, people really do not want to manage potential side effects and get into systemic concerns. So what I would argue is it would -- even with an oral therapy, unless the safety profile is extraordinarily clean, it will not -- it will be very difficult to compete with the IL-4, IL-13 class. And then I want to just briefly talk about oral versus injectable, right? A lot of this has to do with the comfort of the prescriber. And so because we're already comfortable with injectables, that is not going to be a huge challenge, right? So it's whether the prescriber is comfortable getting the biologic injection to the patient. And so then the patient is, "If I can dose it less frequently, I'll do it."" And I think that's the key, right? So many patients would much prefer to do 4 injections a year or 2 injections a year than taking a pill every single day.

Our next question comes from Tazeen Ahmad from Bank of America.

Just to clarify one more point on conjunctivitis. Can you give us what the rates were at 3 months and 6 months? And then you've given us quite a bit of data this morning. So what additional level of data visibility should we expect to see at the upcoming AAD meeting?

Yes, Tazeen. On the conjunctivitis, so we saw similar rates kind of across each arm, and we will be sharing that in follow-up publications, et cetera. But again, no link to exposure, discontinuation rate in line with the class. And overall, 52-week rate in line with the class as well. And we look forward to our Part B data coming up as well where we will look to kind of report out a similarly clean profile as well. In terms of AAD, we're very excited to have the late-breaker. It was a late late-breaker. When we kind of shared this with some of our KOLs, it was -- they were excited to kind of get this out at the AAD, so we were unfortunate to get a spot after the deadline just given that they felt it would be great to get this there, and some calls were made. So really thankful to have the platform because it will help with our upcoming Phase IIIs and getting enthusiasm for that as we're laser-focused on getting those studies going and rolling well and launching in this decade to stay well ahead of any would-be competitors. Carl, in terms of what will be shared?

Yes. I'll add one point to the conjunctivitis piece too, which is what we see is the vast majority of cases actually happen in the first 12 weeks of treatment, and then it kind of tails off after that. This matches what we've seen, especially for lebrikizumab, but also for dupilumab, in terms of the most frequent time of cases, is that first 12 weeks, a little less so the first 6 months. And then after 6 months, it's much more rare to have a case, although you continue to get them over time. I think that, as you said, we've shared a lot here in terms of being disclosive on what we're seeing across the board, safety and efficacy. So I think similar to what we'll be seeing in terms of the AAD late-breaker, potentially with some additional points of contextualizing, what it looks like, and then we'll continue to build on this data set in future conferences as well.

Our next question comes from Salveen Richter from Goldman Sachs.

This is Elizabeth on for Salveen. For Dr. Vleugels, curious what the process will be like for choosing kind of which patients do the 6 months dosing versus 3 months, and overall kind of who you think will be best suited for each of those dosing frequencies? And then for the team, wondering if you guys have plans to evaluate a comorbid asthma population, and based on the data today, if you could extrapolate kind of how you think the comorbid population would do on zumi.

Thank you for that clinical question, I appreciate it. And so here's how I would frame this, because we do have experience in thinking about this in dermatology in terms of having a few different medications where we have 2 options available. So first and foremost, from the data we saw today, either regimen is still a game changer for atopic dermatitis, right? It's just such a difference from the current dosing schedule of 2 to 4 weeks that the best agent I have in psoriasis is Q-3 months, right? So if I have Q-3 months, my patients are going to be thrilled. If I have Q-6 months, my patients are going to be thrilled. So my preference would be that I get the choice, right? And then the question would be, well, how do I choose? Well, everyone would start on Q-3, and then the people with more mild disease, easier disease to control, maybe they didn't come to you on a bunch of systemic steroid, maybe they didn't come to you on another agent, those are the patients who will get to switch pretty quickly to every 6 months, right? And in fact, some patients may choose that at the outset. They might say, "I'm willing to do twice a year." But a lot of patients, "My choice would be to be able to use the every 3 months if I need it," right? Because the safety is so clean that what I want is I want to have the flexibility to choose that every 3 months when I want it, that's on label, right? Because of course, we're looking at aggregate data and every patient is an individual, and we do have some patients that just have more severe diseases, and so the fact that I can get this like very impressive deepening, there are some patients where I would still love on label every 3 months, and that's where most of my patients would start. And then if I could get them every 6 months or if that was their preference, I would do it.

And to answer the second part of the question, which was about the asthma-AD overlap, we know this is a very important population overall, somewhere around at least 30% of AD patients have asthma as well. And we're very encouraged not only by the data today, but by what we saw earlier this year in terms of our Phase Ib for asthma, where we also saw FeNO reduction out to 8 months. So really matching what we saw here. In terms of next steps there, we'll talk more about it later this year, but excited to start an asthma trial soon and really tap into that comorbid population so we can really provide the most benefit to the most patients overall.

And just being mindful of time, I wanted to thank Dr. Vleugels for joining us today and, everyone, for your great questions and attention. We -- I'll hand it back over to the operator to close out the call. But I just want to reiterate, we're thrilled at the data today. We were able to share last year the rapid itch and lesional benefit that we know matters to patients and physicians, and then now have a clear path forward for not just maintaining responses with the 3 and 6-month dose, but the deepening that we're seeing to really great levels and even bring EASI-100 into the conversation, because it has not been before. We're thankful for this opportunity and the patients and physicians that made this happen, and excited to share more at AAD. Thank you.

That concludes the question-and-answer session, and this also concludes today's conference call. Thank you for joining. You may now disconnect.