Apogee Therapeutics, Inc. (APGE) Earnings Call Transcript & Summary

Good morning, and welcome to 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'll be making forward-looking statements related to our current expectations and plans for the company as well as our clinical and preclinical programs. These statements represent our views as of this date and should not be relied upon as representing our views as of any subsequent date in the future. Looking at our agenda today, CEO, Michael Henderson will begin the call with an introduction to today's Phase II APEX Part A 16-week data readout and goals for the program. Chief Medical Officer, Carl Dambkowski, will then walk us through the Part A results; followed by Kristine Nograles, Senior Vice President, Head of Clinical Development and Medical Affairs sharing next steps in our development program for APG777. Before moving on to the Q&A, Michael will summarize our vision for building a leading I&I company. The subsequent Q&A will be led by Michael, Carl, Apogee's CFO, Jane Henderson; and Chief Commercial Officer, Jeff Hartness. I'll now turn the call over to Michael.

Thanks, Noel, and thank you all for your time today. We are thrilled to be able to share what we believe are truly fantastic results from the Phase IIa APEX study for 777 in atopic dermatitis, the next step of our ambitious journey to rapidly bringing 777 to patients. This is a landmark moment for the company, as APG777 met or exceeded all key objectives of the study. With this data, we believe we now have a clear path to a potentially best-in-class therapy across many dimensions, including a quarterly or better dosing interval and potentially improved efficacy results versus approved agents. In a moment, we will dive into the data. But first, I want to highlight that the next several quarters are expected to deliver multiple data readouts for Apogee. First, we expect to have the maintenance data from this study in the first half of next year. Second, thanks to strong enthusiasm from patients and physicians leading to faster-than-expected enrollment, we are accelerating the readout of Part B of the study, which is testing even higher exposures of 777 with data anticipated in the middle of next year. We expect this acceleration of APEX Part B will enable us to start our Phase III studies next year, potentially accelerating our time line to a BLA. Lastly, we have now dosed the first patient in our proof-of-concept study, testing our combination of IL-13 and OX40 ligand in the head-to-head study against the market leader, DUPIXENT, one of the largest drugs in the world. As you will see, the results we present today further reinforce our excitement for our combination of the 2 most active biologics mechanisms, and we are currently on track to deliver these results in the second half of next year right after the APEX IIb. The APEX study met or exceeded all of the objectives we had previously set out to accomplish, demonstrating deep and rapid results on measures of both lesion severity as well as itch. We demonstrated compelling efficacy results and statistically significant outcomes across the endpoints of interest, along with a favorable safety and tolerability profile, consistent with what has been previously shown with this class of medicines. We developed 777 in order to test 2 key hypotheses. First, that we can engineer 777 to deliver the same pharmacology as lebrikizumab, but at an every 3- or every 6-month dosing schedule, supported by our 77-day half-life. And second, that if we can further increase the exposure, we can improve on and maximize the clinical efficacy observed with this class of medicine. Today, we present our first clinical data that we believe convincingly support both of our key hypotheses. Whether we look at measures of lesion severity, such as EASI change from baseline, EASI-75 or IGA 0/1 or measures of itch. 777 demonstrated at least comparable benefits to lebri and Dupi, yet with only half as many injection days. To emphasize how exciting these results are, 2 out of every 3 patients that received our drug reached an EASI-75, a remarkable readout for the field. And as you'll see in a few slides, those patients who saw higher exposures experienced an even greater benefit. More than ever, we are excited for the readout of APEX Part B, where we are testing a higher dose that we believe will allow a greater proportion of patients to achieve the exposures we found to be most efficacious in the results we're presenting today. And our Part B readout testing these higher exposures has now been accelerated with a readout expected in the middle of next year. We couldn't be more pleased. 777 delivered, and we believe we now have an opportunity for an upside case with a clear path to a potentially best-in-class medicine that reshapes the treatment landscape for patients and physicians. We have a unique opportunity with 777 to potentially transform the future $50 billion atopic dermatitis market. You've seen this map before, showing the white space that exists. Our data today affirms our prior belief that we can deliver a potentially best-in-class drug that improves on standard of care across both dosing and efficacy. The white space between us and our competition here speaks for itself. While we are thrilled with the Part A APEX results, we are always thinking about how we can continue to innovate for patients. If anyone is going to beat us, we want it to be ourselves. And we have 2 ongoing studies with data coming in 2026 that could show even more promise than today's results. First, our Part B trial testing a higher dose range, includes an even higher exposure arm of 777. You will see in a moment why we are so excited we included this higher dose. Second, our combination study of 777, our IL-13 and 990 our OX40 ligand is being run head-to-head versus DUPIXENT; again, one of the largest drugs in the world. This is the first study of its kind, combining 2 of the most promising orthogonal mechanisms for biologics to continue to drive to higher and higher efficacy. And all of our programs maintain a quarterly or better dosing profile with the goal of ensuring compliance and persistency and improving quality of life. I'll now hand the call over to Carl to walk us through the data in more detail.

Thank you, Michael. I have the great privilege today to share the paradigm-changing results from APG777 in moderate to severe atopic dermatitis. These results are specifically from APEX Part A, which enrolled 123 patients with moderate to severe atopic dermatitis as defined as having an EASI of 16 or greater, a vIGA of 3 or greater and a BSA of 10% or greater. Patients were randomized 2:1 to receive either APG777 or placebo. Patients assigned to receive APG777 got an induction regimen of 720 milligrams at weeks 0 and 2 followed by 360 milligrams at weeks 4 and 12. As a reminder, this regimen was designed to have approximately 30% to 40% greater exposures compared to lebrikizumab. It is worth noting that APG777's induction regimen requires just 4 dosing days compared to 9 for EBGLYSS and DUPIXENT, representing a more than 50% decrease in injection days. With fewer injections and higher exposures, it offers a simple, convenient start for patients while potentially maintaining or improving clinical outcomes and transforming the treatment paradigm. Baseline characteristics and demographics outlined on this slide were generally well balanced and in line with expectations for this patient population. Least squares mean percent change from baseline in EASI score was the primary endpoint for the study. We met this primary endpoint at week 16 with a high degree of statistical significance, showing both a substantial absolute percent change from baseline greater than 70% as well as a substantial placebo-adjusted effect, surpassing those observed in the registrational programs of DUPIXENT and EBGLYSS. Moreover, lesion reduction was rapid after APG777 treatment, showing significance as early as week 2. EASI-75 measuring patients who achieve a percent change from baseline in their EASI score of 75% or greater is the endpoint in atopic dermatitis that physicians cite as the most important for comparing efficacy and communicating with patients. With APG777, 2/3 of patients, or 66.9%, showed an EASI-75 response by week 16 and a placebo-adjusted rate of 42.5%. No other biologic has demonstrated higher response rates both on an absolute basis or a placebo-adjusted basis in a global placebo-controlled 16-week study. To put the magnitude of this result into context, here, you can see a non-head-to-head comparison of APG777 to other agents, including DUPIXENT and EBGLYSS. APG777 stands out with absolute data greater than 15 percentage points above current standard of care and improvements in placebo-adjusted EASI-75 as well. We believe this result will be very compelling for patients, physicians and payers, especially when being delivered by a biologic with the potential to be dosed substantially less frequently. IGA 0/1, which measures changes in IGA score to 0 or 1 with at least a 2-point decrease from baseline is a key secondary endpoint for the study. Here, APG777 was statistically significant as early as week 4 and maintained throughout. Our absolute results and the curves over time are highly consistent with leaders in the field. Similarly, EASI-90, measuring patients that achieved a percent change from baseline on their EASI score of 90% or greater, showed statistically significant changes with consistent absolute results to leaders in the field. Itch is a bothersome symptom for patients suffering from atopic dermatitis. Patients want both fast and deep itch relief. APG777 showed both with statistically significant decreases in itch as early as week 1 after starting APG777 and showing a more than 50% decrease from baseline at week 16, which is comparable or numerically superior to competitors, including NEMLUVIO with topical corticosteroids and notably, this result for APG777 was without topical corticosteroids. We conducted several additional analyses around EASI-75 to understand the robustness of the result. We used an as-observed analysis, which does not treat rescue medication users as nonresponders like in our primary analysis. Regulators often look and ask for this analysis to ensure the robustness and consistency of the results. Here, the results are even more impressive with an almost 75% absolute EASI-75 responder rate and an almost 50% placebo-adjusted rate. Fortunately, DUPIXENT performed the similar sensitivity analysis method, which is provided as a non-head-to-head comparison. For clarity, EBGLYSS data is not publicly available for this analysis method. In this prespecified analysis, we also looked at efficacy in subpopulations of patients that were either moderate or severe at baseline as defined by their baseline EASI score. We saw very consistent results regardless of baseline EASI score. It is encouraging to see a robust efficacy results in both subgroups, including those with severe disease. To examine the exposure response hypothesis, we were testing an APEX Part A and continue to test in APEX Part B, we performed a post-hoc analysis to look at the relationship between exposure and response. Exposure quartiles were constructed based on average APG777 levels during the induction period. A consistent exposure-dependent relationship was seen across relevant endpoints with higher exposure quartile showing the most robust efficacy results. Notably, in the top exposure quartile, 17 out of 19 patients achieved an EASI-75 response and their exposure approximates the average exposure of the top dose we are testing in APEX Part B, now with an accelerated readout planned for mid-2026. APG777 had a promising safety profile and was well tolerated. IL-13 inhibition is a mechanism with a well-established and favorable safety profile, which was seen from APG777 as well. Overall, the rate of treatment-emergent adverse events was lower in APG777 exposed patients compared to placebo. The most common adverse event is non-infective conjunctivitis, a well-described adverse event for the class. The only other 2 adverse events occurring in 5% or more of patients are upper respiratory tract infection and nasopharyngitis, both numerically lower for APG777 exposed patients compared to placebo. Conjunctivitis is a known benign adverse event that has been seen with all agents in atopic dermatitis that target either IL-13 or IL-4 receptor alpha. For APG777 patients experiencing conjunctivitis non-discontinued adjusted dose or interrupted dosing. The vast majority of cases resolved while patients remained on drug with just 3.7% of APG777 exposed patients having ongoing conjunctivitis at week 16. Cases were also short in duration with a median time of 29 days. Similar to EBGLYSS and DUPIXENT, we did not observe any evidence of a relationship between exposure and conjunctivitis. Importantly, for APG777, there were 0 injection site reactions in the study. Injection pain, swelling and redness can be a reason patients decide to discontinue taking their medication. And for DUPIXENT, it was the leading cause of discontinuation in some studies. The fact that we saw 0 injection site reactions for APG777 in this study further enhances the potential decrease in injection burden for APG777, having just 4 dosing days over the induction period and potentially only 2 to 4 doses per year in maintenance. In conclusion, APG777 demonstrated a promising safety profile and was well tolerated as expected based on mechanism. Now I'll turn it over to Kristine Nograles, who will discuss the APG777 development program, starting with the maintenance portion of APEX Part A where we are testing every 3- and 6-month dosing of APG777.

Thanks, Carl. I am really excited about these results and look forward to our next clinical readouts. First, for APEX Part A, where we are testing every 3- and 6-month maintenance dosing; and second, for APEX Part B, where we are testing even higher exposures compared to Part A. Our next major readout for APEX Part A will be for the week 52 time point, where we are testing maintenance dosing of every 3 and 6 months. Patients on APG777 who complete the induction period are randomized 1:1 to receive either 360 milligrams of APG777 every 12 weeks or every 24 weeks. Patients who received placebo during the induction period will receive APG777 in the maintenance period. The week 52 data for Part A are expected in the first half of 2026 and could confirm the potential for best-in-class dosing of every 3 months or better in the maintenance setting. Before we move on to discuss APEX Part B that is currently ongoing, I would like to reiterate the highly differentiated characteristics of APG777. Not only do we believe that we have a well-tolerated agent with a very promising safety and efficacy profile, we can potentially reduce the injection burden to as few as 2 to 4 injections per year in the maintenance setting. This represents approximately 70% to 90% fewer injections compared to current standard of care maintenance dosing. This alone would represent a huge improvement over current standard of care. We know, from conversations with patients, caregivers and physicians that they want fewer injections, and now we have the potential to deliver that without compromising on efficacy or safety. As a reminder, the APEX study was designed to be an operationally efficient 2-part study that integrates both proof-of-concepts and dose optimization components. Part B, which has been enrolling since earlier this year, is the placebo-controlled dose optimization component with a planned enrollment of approximately 280 patients randomized evenly to high, mid or low dose APG777 versus placebo. As you can see here, our Part B high dose is testing higher induction exposures compared to Part A and is modeled to have 90% to 100% greater exposures than EBGLYSS. It is also similar to Part A quartile 4 that showed the best clinical responses in the exposure response graphs that Carl described earlier in the presentation. We think this gives us the best chance to ensure we are not leaving any efficacy on the table prior to going into Phase III. The primary endpoint of Part B is EASI-75 at week 16, and the secondary endpoints include EASI-90 and IGA 0/1 at week 16. We initiated enrollment for APEX Part B shortly after we completed enrollment in Part A. And due to strong enrollment and enthusiastic support from sites, we are pleased to share that APEX Part B is currently ahead of schedule. This enables us to accelerate the planned APEX Part B induction readout to mid-2026. I'll now turn the call back over to Michael to discuss our plans for building a leading I&I company.

Thank you, Kristine. I want to use this slide to remind everyone just how important and derisking we believe this data is for our long-term success. On the left, you can see the correlation between Phase II and Phase III efficacy and third-party atopic dermatitis trials. Not only is there a very strong relationship, but historically, 100% of programs with positive Phase II data have had successful Phase III trials. And interestingly, the historical data tells us that key efficacy endpoints actually improve on average from Phase II to Phase III for other agents, giving us high conviction and reproducibility. As a reminder, many of the comparisons we walked through today are for our Phase II data versus competitor Phase III studies. We look forward to kicking off our Phase III studies next year. We are thrilled with the results from APEX and are excited to continue executing and build on these results as we push to advance the field and patient care even further. It has been a great start to the year for Apogee, and we think next year could be even more impactful. We are encouraged by the strong momentum in Part B of the study and are looking forward to confirming the profile seen today while also testing a higher dose that matches the highest exposure from Part A. With those results in hand, we plan to initiate our Phase III program next year, subject to regulatory alignment. We also are looking forward to reading out our combination study, which is currently dosing patients and being run head-to-head versus DUPIXENT, another opportunity to deliver even further differentiation for atopic dermatitis patients. Lastly, we have additional respiratory products progressing through early studies that we are also planning to advance and look forward to Phase I data for our TSLP program later this year. This is a landmark day for Apogee. With the Part A APEX data in hand, we have now demonstrated a high degree of differentiation from our competition. This gives us the opportunity to transform the standard of care in the future $50 billion atopic derm market. There is a lot more that we are excited to do with 777 as well as with our broad immunology pipeline. We're looking forward to many additional readouts over the coming quarters to continue to deliver potentially best-in-class medicines across a wide range of I&I disorders. I will now hand the call back over to the operator to begin Q&A. Thank you.

[Operator Instructions] Your first question comes from the line of Seamus Fernandez with Guggenheim.

First, let me just extend my congratulations to the entire team for really a phenomenally executed clinical program and very comprehensive data analysis here. In terms of just a couple of questions that we're getting from investors this morning. Can you just help us understand a little bit of the dynamics with the placebo between weeks 12 and 16. It looked like there was a bit of a rise there for the IGA 0 and 1. Just interested to know what impact that may have had and how that can be managed in the full Phase III clinical program? It looks though that the EASI-90 really kind of may disabuse folks of a concern there just because of the strength of the EASI-90 data that obviously looks extremely strong there. And then as it relates to the exposure response relationship, can you just remind us what the magnitude of exposure was predicted to be in Part A versus lebri? In this study, it sounds like you're clearly pursuing a much higher potential exposure to really pursue that exposure response relationship in the Part B section. So I just wanted to just clarify what that relative exposure was in the Part A induction versus what we're likely to see in Part B. And with those questions, I'll jump back in the queue.

Great. Thank you, Seamus. Really appreciate the questions. On the placebo kind of week 12 to 16 and IGA, I'll hand it to Carl, and then we'll jump to the second question on exposure response.

Yes. Sounds great. And again, thanks for the question. I think, obviously, we're really excited about the data across the board with really standout results in EASI-75, but also across other time points. This is a smaller proof-of-concept study. We see a couple of interesting small data points, IGA, placebo rate, not necessarily absolute, but placebo rate at week 16 being one of them, where we saw a big jump between week 12 and week 16 in the placebo rate. I think that's probably really attributable to kind of the small end of the placebo arm in this study and kind of random fluctuations there. And if you look over kind of the whole time course of IGA, you can see at week 12, really stellar results there above 35% on IGA on an absolute basis and approaching 30% on a placebo-adjusted basis. And over the whole course of the 16-week period, we're tracking with lebrikizumab at some time points slightly better than them and then at some time points, just minor numerically different than them. So again, I think that's really due to kind of the small size of the study. And as we move not only from Part A to Part B, but eventually to Phase III trials, I think there's 2 components in Part B of the study that will really help with that, which are, one is the placebo arm, which is almost twice the size in Part B. I think that's an important factor. And then secondly, the distribution of countries and sites that we're using in Part B that has a much more European focused. For Part B, we're adding over 40 more sites in 6 additional countries in Europe, which has historically had the lowest placebo rate. So we think both of those will be important factors moving forward.

Yes. And on your second question around kind of the exposure response, right? This is the key hypothesis that we wanted to test in the beginning. Our kind of view is that, right, differentiation on dosing would be transformational for the field. And with this Part A, we tested 30% to 40% higher exposures than what lebrikizumab, EBGLYSS is labeled for. And I think that we're seeing, right, especially on the more sensitive endpoints change from baseline in EASI and EASI-75, which is what 70% of physicians look for on an absolute basis to guide their decision making, right? We're seeing really exciting results that get us excited that we have dosing and efficacy on the table. It was important for us kind of throughout to make sure that we're running the proper experiment and fully testing what is the full range of exposure response for IL-13 inhibition. So in the Part B the mid-dose is the part A dose, that 30% to 40% higher exposure and the top dose is 90% to 100% higher exposure. And importantly, that is roughly equivalent on a C average basis to what that quartile 4 showed in the exposure response data that we put up in. We know from FDA, we know from EMA that there is an exposure response for IL-13 from the review documents. This is kind of our first chance to have the richness of the data from our own study. And it -- we find this is very, very provocative, right? We're very excited now to be testing that higher quartile 4 exposure in both the Part B of the ongoing study top dose, and that's also the 777 dose that we're testing along with OX40 ligand in our combination head-to-head versus DUPIXENT.

Your next question comes from the line of Akash Tewari with Jefferies.

Great results here. A few questions on my end. On the exposure response you saw in your trial, roughly what were the weight cutoffs for the quartiles and how surprised were you to see that kind of jump in IGA for quartile 4? Was there something unique about its baseline characteristics, perhaps severity that could have driven that benefit? Maybe stepping back also, can you comment on baseline severity and geographic variability for the trial overall? It did look like placebo came out a bit higher than I think what we had internally expected. And then finally, when we're thinking about that Phase II head-to-head against DUPIXENT for next year, do you think OX40 will be additive on the more stringent endpoints like EASI-90 and the IGA 0/1 when combined with IL-13?

Thanks, Akash. I appreciate the questions. In terms of the exposure response to kind of the weight cutoff, do you want to take that on the first, Carl?

Yes, happy to, right? So the exposure quartiles that we showed were constructed purely based on the APG777 average exposure levels over the first 16-week period. So not necessarily any weight cutoff. However, right, I think, Akash, as you're pointing to, there is an inverse relationship between exposure and weight, meaning as weight decreases, exposure increases for us, but just monoclonal antibodies in general. And so we do see quartile 4 has a lower weight on average than the overall study, but that's really just related to just the exposures we're seeing in those patients. And if you expand from quartile 4 to quartile 3 as well, I think, which also showed really strong results, especially in percent change from baseline in EASI and EASI-75, you see quite a distribution of weight across there. On your second question related to that, which was baseline severity across the quartiles in terms of exposure quartiles, we see a really nice distribution or similarity in our severity across those quartiles. If anything, quartile 3 and quartile 4 had slightly more severe disease on a baseline EASI basis. So a couple of points higher than maybe the lower quartile. So nothing significant, but maybe slightly higher baseline severity in those top 2 cohorts.

Yes. And I think what was important to us was to see the kind of the sensitivity analysis that we ran show for EASI-75 that we're seeing really robust responses both in the kind of moderate and the severe population, in fact, an improved placebo-adjusted response in that severe population. And then on your third point where OX40 really can help with regard to the endpoints? I think there -- we're still digesting this data, and we're excited that our combos headed, we have a lot to kind of just digest when we think about what that quartile 4 looks like on the deeper endpoints as well, right? We're seeing the quartile 4 monotherapy of 777 get to JAK like numbers even ahead of JAKs and some of these endpoints. So I think as we think about more rapid responses, deeper responses kind of across IGA, 90, but also 75, itch, I think that we're just excited to be running the study so we can find out. The nice thing is that we'll next year get both the Part B high dose results and those combo results in a pretty short amount of time. And as kind of we said during the call, we're already excited about the monotherapy results that we had today for the Part A. And if anybody can improve upon these results, we want it to be us.

Your next question comes from the line of Tyler Van Buren with TD Cowen.

Congratulations on the tremendous data package. I have a couple for you. So given the data, is there a hypothesis as to why APG777 might be significantly better on itch than Dupi and lebri? And the second one is the similar rate of conjunctivitis to Dupi at week 16 is encouraging. But how would you expect the incidence of that adverse event in particular to evolve with much higher exposures in Part B?

Great. Thanks, Tyler. I appreciate the questions. In terms of 777 on itch, I think that when you look at our exposures and if you were to overlay the curves and encourage folks to overlay our curves versus others kind of across the endpoints, we think it tells a very compelling picture beyond just kind of the week 16 numbers as well. On inch, in particular, we see when our exposures are highest with the Part A regimen in that first 4 weeks when we're really 50% to 60% higher versus a 30% to 40% higher on average, we're seeing a really nice and rapid decrease in itch. So we think that we're getting patients as early as week 1 to have a statistically significant impact on week itch. And we're -- I think it is a function of the higher exposures that we're seeing. And of course [indiscernible] down itch quickly, of course, helps with lesion reduction to follow. And then in terms of the conjunctivitis rates and kind of what we're seeing there overall and the exposure, I'll hand it to Carl.

Yes, it's a great question. And we looked at this too in terms of the exposure conjunctivitis relationship for APG777 and saw no exposure conjunctivitis relationship. In fact, quartile 4 seems to have the lowest rates of conjunctivitis among all the quartiles, too. And this is really similar to what we've seen previously with lebri and Dupi data, where there doesn't seem to be any relationship between exposures and conjunctivitis and that's been called out in multiple places. So as we move forward, testing this higher dose with really, I think, strong data from the exposure response analysis we did as well as other supporting data, we don't necessarily expect to see any difference in conjunctivitis or other AEs in Part B.

Your next question comes from the line of Alex Thompson with Stifel.

Let me add my congratulations on the data. I guess now that the next major update here will be your maintenance data at 52 weeks for the Phase IIa, I wonder if you could kind of give us a little sense of putting that data in the context and how we should think about what good looks like for that update? And then more broadly, as you digest these data, how do you be thinking about this in the context of other indications like asthma or EoE? What's the read-through there?

Yes. Thanks, Alex. I appreciate the congrats and the question. In terms of maintenance and what good looks like, I think there, we think that lebrikizumab, EBGLYSS has very strong maintenance data, both maintenance response on EASI-75 and IGA 0/1. So if we can see something in the ballpark of what they see with our ongoing maintenance study, we'd be very happy. We're talking 80% to 90% of maintenance on different endpoints in some cases. And I think importantly, when you compare their maintenance data to DUPIXENT, I think people are seeing this in the real world, it is stronger. So if we can approach what they're doing, we would be very happy. In terms of other indications and how we're thinking about developing the full pipeline of the product potential for 777, we've been pretty clear that we really like what how DUPIXENT pursue their development. They established a dose in derm and then use that for -- to go straight to Phase III expansions in other derm indications. Similarly, they established a Phase II dose in respiratory via asthma, which they then used to go straight to Phase III in other indications like COPD. Then the other therapeutic area where they play is GI. So we're excited to see what we can do an EoE as well where the injection burden is quite high weekly currently and patients are hoping for something more. So Phase II in asthma later this year and Phase III -- sorry, in a Phase II in EoE next year, we're maintaining kind of our guidance to kick off those indications.

Your next question comes from the line of Julian Harrison with BTIG.

Congratulations on these results. First, I'm wondering if you could talk about how much market share in atopic dermatitis you expect 777 to command if these initial results from APEX are replicated in Phase III? And then beyond efficacy, what do you expect payers to be most receptive to in [indiscernible] therapeutic profile? Finally, can you talk more about the rescue criteria in APEX and the differences across key trials that are worth highlighting there?

Yes. Thanks, Julian. And sorry, you just cut out for me on the second question. It was around what payers are looking for, just to confirm?

Correct.

Okay. Great. Thank you for the clarification. Yes, so around market share, there, I think when we've done market testing, I think the results have been very positive. Jeff, I don't know if you want to comment briefly with the -- we haven't actually tested this profile yet.

Yes. So Julian, I would say, first and foremost, we see APG777 as having the opportunity to be the market leader in atopic dermatitis. 94% of patients say that they would prefer APG777 over the available options in the market, and they would take action to be placed on this product. Now that was looking at equal efficacy and a quarterly dose and maintenance. Physicians, more than 80%, said that they would start their new patients on APG777 versus the competitors. To Michael's point, we have not done market research to look at a product that is 17 points better than the standard of care in EASI-75. And as noted earlier, market research is clear that physicians look first and foremost at EASI-75 scores in order to make decisions for their AD patients. We have 2/3 of patients that are going to reach EASI-75 with APG777. This has not been seen before. So to answer your first question, I would say, we expect to be the market leader in the biologic AD space.

And then in terms of payers and kind of what they're looking for, do you want to comment on that?

Yes. And so from a payer perspective, we've said from the beginning, even with equal efficacy, so think about an EASI-75 score of 50, equal efficacy with this transformational dosing, we know that patients and physicians prefer this. We've said that, that in and of itself would be a first-line biologic that in and of itself would be a leader and be looked at positively from payers. And I would point, Julian, to the 2 launches that have recently taken place in the biologics space, one being Lilly's EBGLYSS and the other being Galderma's Nemluvio, both of which are off to really strong launches. And if you look at EBGLYSS, they have quickly captured over 80% access in the commercial space. And really, that's with limited differentiation versus what we're bringing to the market. So we expect to have early first-line access and a strong out-of-the-gate launch with both volume and share.

Third question, rescue criteria. Carl, do you want to speak to how we treated patients using steroids?