Apogee Therapeutics Aktie

Good day, and thank you for standing by. Welcome to the AbbVie Investor and Analyst Conference call. [Operator Instructions] As a reminder, this call is being recorded.

I would now like to introduce Ms. Liz Shea, Senior Vice President, Investor Relations.

Good morning, and thank you for joining us for this special conference call to discuss AbbVie's acquisition of Apogee Therapeutics, which we announced earlier today. Joining me on the call today are Rob Michael, Chairman of the Board and Chief Executive Officer; Roopal Thakkar, Executive Vice President, Research and Development, Chief Scientific Officer; and Scott Reents, Executive Vice President, Chief Financial Officer. Joining us for the Q&A portion of the call is Jeff Stewart, Executive Vice President and Chief Commercial Officer. We have posted a set of slides with additional background for your reference, which can be found on the AbbVie investor website.

Before we get started, I'll note that some statements we make today may be considered forward-looking statements based on our current expectations. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in our forward-looking statements. Additional information about these risks and uncertainties is included in our SEC filings. AbbVie undertakes no obligation to update these forward-looking statements, except as required by law. Following our prepared remarks, we'll take your questions.

So with that, I'll turn the call over to Rob.

Thank you, Liz. Good morning, everyone, and thank you for joining us to discuss the acquisition of Apogee Therapeutics. Apogee will bolster AbbVie's leading immunology portfolio by adding multiple differentiated assets across several large and growing disease areas. The acquisition is expected to create significant shareholder value with mega blockbuster peak sales potential anticipated across Apogee's pipeline of assets. This will be enhanced by AbbVie's regulatory and clinical expertise, exceptional commercial capabilities and broad global infrastructure. This transaction is an excellent fit with our strategy to build and advance a compelling pipeline with new sources of growth to support AbbVie's performance in the 2030s and beyond.

Apogee's pipeline is highly complementary to our development strategy in immunology, where AbbVie is the clear industry leader. For more than 2 decades, we have focused on redefining the standard of care with differentiated therapies across a broad set of diseases. And SKYRIZI and RINVOQ have delivered on that objective with development programs either approved or ongoing across more than a dozen indications. This includes numerous positive head-to-head studies versus other novel orals or biologics. And while both products are expected to grow well into the next decade, our goal is to ultimately launch new medicines that offer higher efficacy, greater convenience or even a functional cure. AbbVie's existing immunology pipeline includes unique combination platforms, long-acting and bispecific antibodies, novel orals and B-cell depletion approaches. These are all strategically being developed to substantially raise the bar for efficacy and convenience to further improve patients' lives.

And Apogee's pipeline further augments our efforts, adding multiple differentiated assets for potential treatments in dermatology, respiratory and other related inflammatory diseases. We are especially excited about zumilokibart, which has a potential for a best-in-category profile with strong efficacy and significantly improved convenience in atopic dermatitis, along with multiple indication expansion opportunities. This adds even more depth to our robust pipeline in immunology, which we expect will be a major growth driver for AbbVie over the long term. In addition to immunology, we expect to drive growth across multiple areas of our diverse portfolio. In neuroscience, we have strong positions in psychiatry, migraine and Parkinson's with each having $5 billion-plus peak sales potential. And with our next-gen assets, bretisilocin, emraclidine and 932, we see meaningful opportunities to further augment our growth in psychiatry well into the next decade.

In oncology, we are making excellent progress across both heme and solid tumors. Our late-stage assets, [indiscernible] and [ TMB A ] each have multibillion-dollar peak sales potential, and we are advancing several other exciting ADCs, including 706 and 969 following encouraging mid-stage data. In obesity, we continue to advance our EMA-led program, which also has the potential to drive strong long-term growth for AbbVie, complemented by our commercial footprint and capabilities within aesthetics. In summary, this transaction represents an extremely compelling opportunity for AbbVie, Apogee and our respective shareholders, and importantly, for patients.

With that, I'll turn the call over to Roopal, who will highlight Apogee's clinical programs in more detail. Roopal?

Thank you, Rob. This transaction adds a portfolio of novel long-acting antibodies that further strengthen our immunology pipeline. AbbVie has more than 2 decades of experience developing differentiated therapies in immunology. Our leadership is a result of our deep scientific expertise and our commitment to deliver innovation that improves patients' lives. We have demonstrated an impressive track record across a broad range of autoimmune diseases that have redefined the standard of care with HUMIRA, SKYRIZI and RINVOQ.

We continue to pursue next-generation therapies that have the potential to set an even higher bar for efficacy safety and convenience. AbbVie's current immunology pipeline is very robust and includes several innovative programs to address unmet needs across various diseases, including combination approaches in IBD evaluating SKYRIZI with our alpha 4 beta 7, TL1A and potentially TREM1 as well as novel combo programs across rheumatology and dermatology, longer-acting antibodies, including a new anti-IL-23 for psoriasis. Several bispecifics, including lutikizumab and an anti-IL-13/31 and IL-13/18. Oral agents, including an anti-IL-23 and in IRAK4 and LPAR1 inhibitor. Also a B-cell depletion program, including our novel in vivo CAR T as well as anti-CD19 antibodies.

Apogee's pipeline is highly complementary to our immunology development strategy and adds a portfolio of long-acting high-efficacy novel biologics targeting dermatology respiratory and other immune-mediated diseases. Apogee's most advanced asset is zumilokibart, an extended half-life anti-IL-13 antibody with a lead indication in atopic dermatitis, where it has demonstrated strong lesion and itch control across a robust 2-part Phase II study. In Part B of the study, zumilokibart demonstrated high response rates across key efficacy endpoints at 16 weeks, including EASI-75, EASI-90 and importantly, improvement in itch, which is particularly bothersome for patients. Results from Part A showed durable maintenance of response for 1 year with sustained efficacy for both every 3-month and 6-month dosing. The extended half-life enables a substantially lower injection burden for patients relative to currently available biologics.

Additionally, zumilokibart was well tolerated across the Phase II program with a favorable safety profile. Phase III studies in AD are expected to begin in the second half of this year. with readouts anticipated in 2028 and regulatory approval in early 2030. Given the potential best-in-category profile, including strong efficacy and convenient dosing, we believe zumilokibart has the potential to become the preferred early line therapy for moderate to severe AD, which would be a highly complementary offering of RINVOQ, a very effective oral option for AD patients not adequately controlled with other systemic drugs, including biologics. In addition, zumilokibart could potentially expand to other indications where IL-13 plays a critical role. We plan to begin development as a monotherapy in prurigo nodularis, chronic pruritus of unknown origin, eosinophilic esophagitis and chronic spontaneous urticaria.

We anticipate a steady cadence of data readouts across these indications over the next several years with potential approvals beginning in the early 2030s. Another exciting asset from Apogee is APG273, a combination of zumilokibart and APG3i and anti-TSLP antibody. This combination has the potential to provide transformational efficacy in type 2-low and high asthma along with an extended dosing interval. We plan to begin clinical studies in asthma soon with potential launch in the mid-2030s. In parallel, we also plan to explore development of 273 in COPD and chronic rhinosinusitis with nasal polyps. In summary, Apogee's differentiated portfolio is a strong strategic fit for AbbVie. These promising new assets span indications across dermatology, respiratory, and other related inflammatory diseases and meaningfully add to our deep immunology pipeline.

With that, I'll turn the call over to Scott.

Thank you, Roopal. This acquisition provides AbbVie with multiple high-value pipeline assets, which further strengthen AbbVie's prospects for long-term growth. Under the terms of the proposed deal, AbbVie has agreed to acquire all outstanding shares of Apogee Therapeutics for $135.11 per share in an all-cash transaction. This reflects a total purchase price of $10.9 billion with an implied transaction value of approximately $10.1 billion, net of estimated cash and marketable securities acquired. We will fund the deal with debt.

We see the potential for significant shareholder value creation with mega blockbuster peak sales potential across Apogee's pipeline. Zumilokibart in atopic dermatitis represents the most substantial component of the deal value given the data generated to date and highly differentiated profile potentially. More modest value has been ascribed to APG273 given the earlier stage of development. This is a financially attractive transaction for AbbVie. We anticipate earnings accretion beginning in 2032 and significantly ramping over the long term. Assuming a deal close in the third quarter of 2026, we anticipate the transaction to be approximately $0.14 dilutive to our adjusted earnings per share in 2026 and approximately $0.46 dilutive to earnings in 2027, reflecting the full year impact of new expenses and deal financing.

Additionally, we intend to exercise the buyback option for change of control under the Apogee revenue share agreement with Blackstone Life Sciences to reduce a significant portion of the expected future royalty obligation for zumilokibart. Lastly, it is important to note that there is no change to our capital allocation priorities. We remain committed to a strong and growing dividend and continue to add the financial flexibility for additional business development. We also do not anticipate a change to AbbVie's credit rating as a result of this transaction as we are committed to achieving a net leverage ratio of 2x within 2 to 3 years following the Apogee deal closing. In summary, this is an exciting day for both AbbVie and Apogee. Together, we are developing a complementary immunology portfolio that has the potential to deliver better outcomes for patients, and significantly bolsters AbbVie's already strong prospects for long-term growth.

With that, I'll turn the call back over to Liz.

Thanks, Scott. We will now open the call for questions in the interest of hearing from as many analysts as possible over the remainder of the call. [Operator Instructions]. Operator, first question, please.

Our first question comes from Chris Schott from JPMorgan.

I just wanted to dig a little bit more into how much of this deal is based on this initial AD indication versus the potential broader suite of IL-13 indications you could pursue here? And maybe as an adjacent question to that, do you believe you'll be able to get formulary access and dislodge share just with an AD label? Or do we need to build out a number of these core Dupixent indications before you get meaningful uptick of the drug given the breadth of the DP indications and some of the comorbidities we see with these patients?

Sure. Chris, this is Scott. I'll start with the first question and then maybe turn it over to Jeff on your second question regarding access. So as I said in my remarks, the majority of the value is associated with zumilokibart. And with respect to indication wise, the bulk of that relates to AD as well. So we've not ascribed a certain percentage to it. Obviously, we're going to go through our analysis, and you'll see some disclosures on our opening balance sheet when we issue that and the deal closes. But the bulk of the sales are associated with both zumilokibart and the AD indication.

Chris, it's Jeff Stewart from Commercial. No, we don't believe that we would have to wait until sort of we complete the full construction of, let's say, similar to the Dupi label. We think that we're going to have quite a differentiated product here. We particularly like sort of the idea of the Dup plus efficacy. We think we can reproduce that in Phase III obviously, the best-in-class convenience. And then you have to remember that at least for the payers, we have a large footprint of other immunological agents that we think that we can carve out the right amount of access here to get off to a fast start.

Next, we'll go to Terence Flynn from Morgan Stanley.

Great. Maybe just to follow up on that question. Are you guys considering any head-to-head trials in atopic dermatitis or potentially asthma? And then maybe just on asthma, elaborate on the next steps there and the commercial opportunity, as I know that would be a newer area for you guys. So what would it take from a commercial standpoint?

Terence, it's Roopal. At this stage, we haven't ruled out the need for head-to-head, although it may not be necessary based on the data that we've seen to date, especially given the dosing interval and convenience and potential impact on adherence, particularly in atopic dermatitis.

One consideration is also if you have an installed base of patients that are inadequately controlled, having them switch over to something that's much more convenient, that's an option that could be meaningful and one under consideration. You've seen us conduct such studies with RINVOQ and SKYRIZI, and those have been quite impactful and affect day-to-day practice patterns. So I would say that continues to be an option that we're going to explore. And asthma, as you stated, it's potentially as big or bigger than atopic dermatitis, especially continues to see quite a bit of severe patients. The penetration rates like in atopic dermatitis are under 10%, and you have prevalence in growth rates that are exceeding 15% similar to atopic dermatitis. So the opportunity there is large and these patients are underserved at this stage and having a combination approach may fulfill that unmet need.

Maybe just to add to that, Terence, it's Jeff, is that we had a stated goal during our strategic reviews to enter the asthma in the respiratory market. We have a very, very significant commercial footprint. And to Roopal's point, our ability to think about novel biologics or combination platforms as we look at what we believe is a severely over-indexed market to the inhalers. And look, that makes sense when you don't have maybe the biologic horsepower you have in other areas but we think that, that will come, and we want to be on the front end of that. So that was a very purposeful aspect to enter asthma with this acquisition.

And this is Rob, just to add to Jeff's comments. As I think about the size of the company in the middle part of the next decade, as a management team, we looked at are there new sources of growth in large markets with high unmet need. I've mentioned obesity in the past, and you saw us enter into that with the analog opportunity from [indiscernible]. And with this opportunity now in asthma is another disease area that we evaluate as again, large market, high unmet need that can really drive growth for the company over the long term.

Next, we'll go to Vamil Divan from Guggenheim.

Congratulations on the deal. So maybe 2, if I could. One, just on the atopic derm just maybe you touched on this at the beginning of the call, but just the presence of RINVOQ in that indication, kind of how you think of the overlap between that and now what you're getting from Apogee? Do you have any concerns from an FTC perspective on that overlap there? Maybe you can just remind us how much of it looks feels like to come from [indiscernible] that would be helpful. And then second, just maybe building on those prior comments that was interesting is you just as a new area that you wanted -- that you strategically want to get into. I'm just curious about sort of pulmonary and general and respiratory in general, broader than ASO.

We've seen a lot of interesting development in that space as you sort of build out that vertical now. Is this a new area we should think about where you may be looking for further business development in the future?

Vamil, it's Roopal. With respect to RINVOQ and AD, I mean, first of all, it's a atopic dermatitis is a very large market. And as we stated, it's growing at over 15% per year. If you think about moderate and severe and compare it to psoriasis, it's about 2x, 2.5x larger than psoriasis. And there's many assets and we acknowledge it's quite competitive. However, that being said, we see RINVOQ in second and later lines. And consistent with IBD where you see SKYRIZI, a preferred therapy in earlier lines, you see RINVOQ been able to come in now in second and later lines. So that positioning is also observed in psoriatic arthritis.

It's also a position that we're developing against in hidradenitis suppurativa with lutikizumab and RINVOQ. And consistent with that, zumi here could be in the front line a preferred agent. And for those that are not getting the relief that they need, you have RINVOQ there. And I think that creates a very nice opportunity, and you've seen quite a bit of success from us, and I'll let Jeff comment further on that.

Yes. I think, Vamil, to Roopal's point, we don't see a material impact on RINVOQ. In fact, we think it's going to help because our ability to deliver across other therapy areas like PSA or IBD, sort of this one-two punch where you have a biologic and then you have RINVOQ in the later lines, has been very, very successful. So we don't see significant interactions, if anything, they're positive. And I think it's important to remember, as Roopal intimated, that the label in the United States is that RINVOQ should be used after systemic exposure, including a biologic. And obviously, strategically, we want that biologic to be zumi. So all good from this dynamic of the ability of our commercial teams and our sales teams to appropriately co-position the assets based on their data and their labeling.

And back to the asthma question and respiratory. We also have plans to go into COPD. There's more than 2.5 million patients there. And also the penetration there for advanced therapy is even lower than what we are observing with atopic dermatitis and asthma. So we see opportunities there -- and we continue to see consistent overlap with some of these other indications that I mentioned with asthma as well. As it pertains to going beyond, recall we have LPAR assets biologics and small molecules that just initiated development in idiopathic pulmonary fibrosis. So that is several indications in respiratory and we don't rule out any others because we do agree there continues to be high unmet need in the therapeutic area of respiratory.

Next, we'll go to Mohit Bansal from Wells Fargo.

Congrats on the deal. My question maybe for Roopal here. Just trying to understand like what is in this particular IL-13 biology that you think could actually provide differentiation efficacy or maybe a better efficacy than Dupixent because Dupixent is IL-13 and IL-4. So there is that aspect, which like maybe some KOLs are saying that maybe when you do the Phase III trial, the efficacy could be more similar than different. So in that case, it is a convenience play, but would love to understand how you are thinking about biology and how it could be differentiated in terms of biology that results into better efficacy.

Thanks, Mohit. It's Roopal. Yes, that's a good question and something that we've been considering for some time as we've developed our internal pipeline. However, when we look at the data and the amount of ability of zumi is to saturate IL-13, it takes it down to 99%. And then when you look at the Phase II data, and there's 2 parts of that. So you see a replication. You see quite high efficacy. And in our own internal work, we feel 13 is the critical factor in atopic dermatitis. That's why we have a 13 31 and 13 18. And also, we have optionality with Apogee's pipeline. They, in fact, have an extended duration IL-4 alpha receptor and, in fact, an extended duration IL-31. So that creates a lot of options.

And now the data, I would say, is most critical. We can talk about preclinical hypotheses. But at the end of the day, the data is most important. And the Part B where you saw maybe a little bit better efficacy was in a broader population, a global population one that had failures and approximately 20% of the patients of advanced therapy that would include Dupixent, JAK inhibitors like RINVOQ. So that, we believe, is more consistent with what a Phase III program would look like. We also have the opportunity during diligence to look at the data, to look at PK and exposure data we run models, we use machine learning. And we think there's a very strong probability to replicate and continue to see high efficacy. The other notable item is the EASI-100 response that you see with Zumi, we didn't talk much about that. It's in the package that you'll see posted. But that is actually quite high. And some of that starts to get close to RINVOQ like efficacy for EASI 100.

It's not going to be exactly there if we did a head-to-head apples-to-apples comparison. But it's certainly lifting and it's lifting much higher than what we've observed previously, if you're simply blocking IL-4. Mohit, if you think back years ago, when IL-12/23s were making their way into psoriasis and there was some thought that you had to take out more cytokines. We even had our own program in IL-12/23. And ultimately, we thought taking down maximally IL-23 was going to be the path forward in psoriasis. And I think you've seen that play out with the success of SKYRIZI. So we don't -- we're not concerned, and we're very excited to move this into Phase III.

Next, we'll go to the line of Michael Yee from UBS.

Congrats on the deal. One of the things I know that's been out there in terms of half-life extension programs has been the YTE modifications. Can you remind us and perhaps explain some of the strong diligence you might have done on that? And to what extent you got comfortable with these types of product profiles and the outlook ahead and what your assumptions are around IP?

Michael, it's Roopal, I'll take that one. You're right. Some of the work has to be in molecular design, and we do have a level of comfort. However, you don't always know how the antibody is going to act when in human, in disease. So that's what's most important.

So when we look at zumilokibart, we do see an extended half-life in human disease over 70 days. So that gives us confidence that whatever molecular design there was hasn't impacted any performance that you would see in the clinic. And you couple that with the high efficacy that we discussed, including EASI 100 gives us comfort that we have the option here potentially to go to twice a year and maintain very high levels of efficacy, especially if we match the PK some of the data that you've seen that goes to every 24-week dosing in terms of the maintenance of response that's fairly strong. However, that was not -- the PK wasn't matched. That was at 360. So if we double that dose to match the PK, then we have greater confidence in the ability to get to [indiscernible] 24. So then that further validates that concept of TE. But I believe you have to consider the performance of the whole molecule where it comes to binding of the critical epitopes and take down of the cytokine of interest as well as half-life. And we see both of those playing out when we look at Part A and Part B of the data to date.

And maybe just to supplement that from the diligence perspective on the commercial side, obviously, we have very close connections to the community derms and the thought leaders around the world. And because of the strength of the data, I mean, it's Phase II data, we can see the Part A, we see Part B. We can see the consistency and the durability this opportunity for 3 to 6 months of dosing, it was overwhelmingly viewed as a high, high willingness to prescribe by the community derms.

And I think it makes a lot of sense because when you think of this group of physicians, it's something that they know, they understand and they know an IL-13. It looks quite a bit better in this Phase II work that we believe we can reproduce in Phase III, and it's quite a bit more convenient. So that idea of something I know that's better and more convenient was tied to a very high willingness to prescribe in our commercial diligence.

And Michael, this is Rob. On your question for the outlook for IP on these assets. We see that well into the for zumi, the compound patent, we have expiring in 2044 and then for APG273 compound patent in the U.S. expiring in 2047. So there's quite a bit of runway for both assets.

Next, we'll go to the line of Emily Field from Barclays.

I was just curious how you're expecting the commercial landscape in AD to have evolved by the time we could be launching given that [indiscernible] just had the 8-week maintenance dosing added to the label? And then how you're thinking about the potential entry of Dupixent biosimilars and how that could impact from a formulary perspective?

Yes. Thank you. So thanks for the question. So I think one of the things that Roopal mentioned, I believe we've mentioned over time, is that the penetration rate of this market is incredibly low. I mean, like in some ways, we look at how big Dupi can be global sales and the dynamics around RINVOQ. But this penetration rate is about 8%, which is by far the lowest of any immunological category that we see, and it grows the fastest. So one of the key dynamics is this market is going to continue to progress and develop over time. We've highlighted before that you're going to see line of therapy expansion.

So even if you had biosimilars and they came in and they took a piece of the front line. There's still this expansion dynamic and basically biologic growth dynamic that is going to be very, very sustainable. We also looked at the market in a certain way that some of the, let's say, near-term catalysts have dissipated to some degree, which we think gives more opportunity for a knowable product like zumi. So we think the [ OX40s ], for example, are going to run into a lot more trouble. We've seen that. We've seen the discontinuation rate of an early biologic combination with IL-13/31. So we think the space is really there in this expansive approach.

We also view that we've seen in other biologic markets that the first biosimilar does not necessarily sort of take all the air out of the market, particularly one that is frankly so immature. So net-net, when we view all of the dynamics here in the atopic derm market, this is going to be a market that will continue to evolve over the next decades. And the technologies will continue to improve, and we think we have a good one for that early line, and we have a really great one for later lines like RINVOQ. So that's how we viewed the market dynamics.

And maybe from an innovation standpoint, if you think back on HUMIRA, infliximab, ustekinumab, these have all gone biosimilar over the last several years. And with -- when you bring innovation, you still see expansion. And as Jeff explained, the opportunity is still there. So we think from a development standpoint, because of the low penetration rates and underserved market here, these types of innovations here will be rewarded.

Next, we'll go to the line of Jason Gerberry from Bank of America.

Just wanted to follow up on Emily's question. And so your commentary about being a preferred early line therapy in AD. Just wondering how important is it for you to be commercially available on market either at or even before the availability of biosimilars of Dupixent. And in addition to that, I'm just trying to get a sense of your commercial outlook in being a preferred early line therapy. How critical is it to being differentiated on efficacy versus just differentiating on the convenience attribute?

Yes, thanks. In general, and what we've seen, if you look at analogs and models over time, it is important to basically come out ahead of the emergence of biosimilars. It's just aids in payer negotiations and sort of how they may think about their formulary development. I mean one of the most valuable aspects that we looked at certainly when HUMIRA went in the U.S. is we were able to establish SKYRIZI and RINVOQ several years before the emergence of the HUMIRA biosimilars, and you've sort of seen that story play out. So that is an important consideration.

Also, look, it's always better to have a notable efficacy advantage versus just a convenience advantage. Now if you think about the magnitude of the convenience advantage, it's quite significant because we even see -- even with [indiscernible], a significant amount have to go from 1 month down to every other week. Maybe we'd see 30% to 35%. So this is a substantial change in convenience, but there's no question that a critical part of our Phase III development program will be looking at populations to make sure that the biology around the dose, basically a molecule itself can distinguish itself from the first-generation biologics, like Dupixent or Adbry. So yes, you always want to have a plus on the efficacy side as your clinical trial and your programs are able to elucidate that.

And this is Rob. I'll just add that it does depend on the disease area. So for -- as an example, in the disease area that zumi participate in, convenience is an important factor. So efficacy and convenience. But convenience can play in a very important role. But if you think about in IBD, for example, efficacy is it will rule the day more so than convenience. So you do have to look at the disease area participating in to really answer that question.

And with the IP of 2031 with Dupixent or potentially further out, the way these will be designed is that we'll be launching prior to any of that if we're thinking early 2030.

Next, we'll go to the line of [ Jeff Meacham ] from Citibank.

Congrats on the deal. A lot of my questions have been asked, but I wanted to ask you on the dosing. How much of the value or the positioning do you think could be enhanced by moving to even further dosing, say, 1 year, even beyond the 6 months? And are there indications where that annual dosing makes a little bit more sense and maybe could be a priority as you look to further add new trials to the mix here?

Jeff, it's Roopal. There could be a component of patients and individuals that are willing to look at something that could be dosed once a year potentially in derm, I would say, where there's strong safety established. And if the patient has already experienced strong tolerability. I think out of the gate, it could be challenged because you just don't know how the patient is going to do. If they don't perform well, then the question for dermatologists could be, what do I do next if I have an ultra long half-life.

If you have a strong pharmacodynamic effect that sort of punches above the half-life, that could create some options. But we think at quarterly dosing already that is highly differentiated, and you've seen that performance with SKYRIZI. And going to twice a year is quite meaningful because the physicians are going to want to see the patients a couple of times a year. So I don't think if it doesn't achieve an annual dosing regimen that harms these in any ways. And occasionally, you have to be a little bit careful if you go too long.

Next, we'll go to the line of Evan Seigerman from BMO Capital Markets.

I wanted to touch on your thoughts regarding kind of the evolving competitive landscape, specifically with Regeneron, super Dupi as they've talked about kind of their IL-4, but also their IL-13 IL-4 bispecific. How does this asset play with these potential investigational assets given that Regeneron and Sanofi kind of own this space. I know you want to make inroads. I'd love to hear your thinking as you had evaluated this asset in making the decision to acquire?

Evan, it's Roopal. We think zumi can be quite competitive. And you can see the data already. It's posted. It's very strong, and we think we have a high probability of replicating this in Phase III and expanding out to other indications. And it's very important to look at these convenience profiles of this asset. I think that really sets up a strong competitive play. And then I would say going forward, we're not done.

Remember, there's RINVOQ there as well. And as we've discussed in IBD and even in rheumatology, lines of therapy are going to continue to expand. And the market itself is growing. It's very dynamic. It's growing over 15%, Penetration rates are under 10%. So it's a very large market. So RINVOQ is still there. There's a synergy when you have 2 of these assets. We've seen that play out in psoriatic arthritis. You've seen it play out in IBD. Hopefully, we'll see that play out in HS in the future. And then recall with this acquisition, we also pick up a half-life extended IL-31, also an IL-4 in our own pipeline, 2 bispecifics, 13 31 and 13 18. So there's quite a bit more beyond where we're talking. But obviously, the lead asset is zumi, but I would say quite a bit more behind that, given the scale of this market.

Next, we'll go to the line of David Amsellem from Piper Sandler.

I had a question on TSLP in particular, and sorry I missed this in your prepared comments. But are you thinking about the TSLP only as commercially viable given that there is less dosing frequency than Tezepelumab? Are you -- or are you specifically wedded to the IL-13 TSLP directed therapy combination. And I guess that question applies to both asthma as well as COPD? Just wondering how broadly you're thinking about that as you think about TSLP only versus IL-13 plus TSLP.

David, it's Roopal. So some context for our thinking and I'll refer back to inflammatory bowel disease, where we had a very strong asset with SKYRIZI and we felt combining with that could drive higher levels of efficacy. We've outlined an alpha 4 beta 7, TL1A and potentially TREM1.

Now what we did there was look at the 2 mono therapeutics, along with the combination and look at exposure response. And our goal there is to optimize that therapy. And I would say you can consider that work, and that's what we would apply to IL-13 and TSLP. Both are half-life extended. And going forward, we'd want to look at them in parallel and in combination and see where it takes us. We believe the combo could be the best approach, especially targeting TH2 high and low, driving that convenience. Also from a clinical standpoint, do you have to always check eosinophil levels you may not, if you can get the combo and work in all comers. So that's a layer of convenience in and of itself before we start talking about enhancing adherence going to quarterly dosing or twice a year. So it will be a data-driven approach, very consistent with the pattern that we're following in IBD.

Next, we'll go to David Risinger from Leerink Partners.

Let me add my congrats as well on the transaction. So I just wanted to clarify a few things, please. So first, could you comment again on the anticipated timing of product launches? I think, Roopal, maybe it was you that had mentioned early 2030 for product launches, but just wanted to clarify that. And then separately, regarding the leverage, could you define how you calculate leverage and restate, I think you said you target a net leverage I believe that's how you're talking about it in 2 to 3 years of 2x, but more clarification on that would be great.

Sure. This is Scott. I'll start. And actually, I'll take both of them. So you're correct with respect to the launch of zumilokibart early 2030 is what we anticipate. And then with respect to net leverage, so that's our net leverage, we define it as net debt to EBITDA. And I would note that EBITDA does not include IP R&D charges just for clarity. And so when we talk about we've actually have indicated we'd be below 2x at the end of this year. And we've talked about we will have a path back after the borrowing for this transaction to again below 2x within the 2- to 3-year time period. And I think that's pretty standard with how we've talked about managing our overall leverage and the strength of our balance sheet. So our balance sheet remains very strong even after the borrowing for this transaction.

And David, just a real quick comment. Our target is 2030 early. We'll kick off these Phase IIIs this year. But every opportunity the team can have to pull these in into the earlier part of 2030 or even before, obviously, these are levers that we're all going to pull together.

Next we'll go to the line of Gary Nachman from Canaccord Genuity.

This is [ Dennis Resnick ] on for Gary Nachman. Congrats on a deal. Just as it relates to the Phase III atopic derm trial, so to start in the second half, can you just talk a little bit more about the size and the scope of the trial and what you need to do from a Phase III design standpoint to replicate the Phase II success? And then would you have any ability to influence that trial before it kicks off?

Dennis, it's Roopal. Well, we will partner and influence to the extent that we're allowed. But yes, we have experienced here already with multiple Phase IIIs with RINVOQ which were very successful and not guaranteed, but with RINVOQ, we probably saw better efficacy in Phase III than we did in Phase II. So we have confidence in our abilities and we have confidence in the Apogee team for sure.

And why I say that is because Part B was much more consistent with what a global trial would look like, especially if we're trying to balance the right patients, the right sites, the right countries with speed. And the Part B data are reflective of that and look quite strong. And when we go further, as I stated before, using the exposure response data, machine learning and looking at baseline demographics, I think the predictors that we are seeing are very consistent with what was utilized in Part B. So replicating that, I don't think should be a major problem, but we'll be focused on that and partnering to the extent that is allowable.

Next, we'll go to the line of Louise Chen from Scotiabank.

Congrats on elated to ask you, if you could provide more color behind your 2032 accretion assumption and this mega blockbuster sales potential. Maybe if you could give us a little bit more thoughts on sales, margins, market share penetration.

So you're correct. So we talked about being accretive in 2032. Now recall that as Roopal just indicated earlier and I as well, the sales we anticipate to begin after the approval in at least early 2030. So you're going to see positive operating margin in 2031 and then [ DoD ] actually accretive from an EPS perspective in 2032. We've not sized the sales number other than to say the mega blockbuster status that we spoke about earlier in our prepared remarks. But you can anticipate and there's plenty of analogs out there from even recent launches, a fairly steady and important ramp as we launch the product.

And Louise, this is Rob. Just to add. As we think about this acquisition, we're thinking about long-term growth beyond SKYRIZI and RINVOQ. So we would expect that what Apogee gives us is significant, we say mega blockbuster peak sales potential, these are significant assets that can really help drive growth for the company beyond SKYRIZI and RINVOQ.

Next, we'll go to the line of Steve Scala from TD Cowen.

I have 2 follow-ups, including on the question just asked. So Rob, when you say mega blockbuster, I assume that you're implying something north of $20 billion plus. Is that correct? And then secondly, I'd like to follow up on an earlier question, in addition to new molecules, Sanofi has spoken to high-dose Dupixent and Dupixent combinations. Should we assume that AbbVie has considered these carefully and has concluded that they don't offer much? Is that the conclusion we should derive?

Steve, this is Rob. So our definition of mega blockbuster would be north of $10 billion. Yes. And on the competition, yes, we've looked at existing competition new competition. I wouldn't say they don't offer much. I would say it's a very, very large underpenetrated growing market amongst the largest in the class in immunology. And we feel with this asset, it can be highly competitive. And we also believe with the pipeline that will emerge from Apogee, coupled with AbbVie's pipeline, it allows us to be competitive in this dynamic space for many, many years to come.

And for a final question, we'll go to the line of Matt Phipps from William Blair.

Congrats on the deal. Roopal, you touched on this a little bit, but some physician conversations lately have had concerns about the washout time for these YT antibodies for a patient that does develop a side effect such as perhaps conjunctivitis here. How do you manage that in your development plan? And then do you have any concerns on potentially higher rates of conjunctivitis, given deeper and longer coverage of inhibiting out there?

Thanks, Matt. So in terms of conjunctivitis, that was something that we wanted to look at during diligence as well. And what we observed is rates consistent with other therapies. And remember, these patients have a higher rate at baseline to begin with. And I thought the team at Apogee did a very nice job of characterizing this and really trying to assess it over time and after diagnosis was made. And what we observed there was around a duration of approximately a month or so, and that compares very favorably with other assets in the space where the duration of conjunctivitis last much, much longer.

So given the long half-life and short duration, we think the physicians and us with guidance are very well positioned to manage. Also, the key for adverse events is what results next. And the discontinuation rate is actually very, very low. Overall trials, all under single digits and due to conjunctivitis less than 1%. So even with a 70-plus-day half-life these adverse events resolved and largely resolved with eye drops and moisturizing eye drops. So no concerns there, deep diligence. Apogee has done a good job. We are very familiar with this, along with our eye care team, and we think we'll be able to manage this very well and manage these concerns and still allowing this very nice dosing profile that we see.

Thanks, [indiscernible]. That concludes today's conference call. If you'd like to listen to a replay of the call, please visit our website at investors.abbvie.com. Thanks again for joining us.

Thank you all for joining the AbbVie Investor and Analyst conference call. That concludes today's conference. Please disconnect at this time, and we hope you have a wonderful rest of your day.

Good morning, everyone. Thank you so much for joining us. It's my pleasure to introduce the Apogee team. With us, we have Jane Pritchett Henderson, Chief Financial Officer; and Jeff Hartness, Chief Commercial Officer. Thank you for joining us.

Maybe to start here, on the back of a few key data sets that have read out this year, including the 52-week zumi data in atopic dermatitis and recent dose escalation data in the disease as well, can you outline how the company is positioned in the second half and beyond and walk through the key near-term catalysts?

Yes, absolutely, and thank you for having us, Salveen. Apogee is developing zumilokibart, our IL-13 targeting antibody across type 2 inflammatory diseases. Our first priority is moderate to severe atopic dermatitis. It is the largest of the I&I indications. It is growing the fastest. It is the least penetrated. So far, '26 has been a big year for us in terms of data. Our Phase II Part B data that we disclosed last month showed robust efficacy across lesional and itch endpoints with only 4 dosing days compared to 9 with standard of care.

Earlier this year, we reported Part A maintenance data, where not only we showed maintenance response, but importantly, we showed response that continue to improve to 52 weeks, including something very notable, EASI-100, which is very clear skin of over 40% for patients in that maintenance setting. What we're doing next is also exploring pipeline and a product opportunity. At the same time of disclosing the Part B data, we disclosed plans for asthma as well as EoE.

Why did we choose those first? Well, asthma has an approximate 30% overlap between AD patients, and there is a significant need to be able to treat both. EoE, we only have Dupixent out there, which is only -- which is dosed weekly. So two important indications that between the three of them represent over 75% of Dupi sales. And so EoE Phase II will start the second half of this year and our Phase IIb, which is potentially registrational will start in 2027. Also with the Part B, we announced the largest pre-Phase III royalty and debt financing transaction and collaboration with Blackstone. This is important because combined with the $1.3 billion of cash that we have on balance sheet, that capital takes us through not only commercialization for zumi in 2029, but also takes us to potentially profitability.

When we look at the data reported, we have a differentiated profile that KOLs are so excited about as the next first-line product for AD patients. And again, we look to launch that by the end of the decade. Beyond zumi mono, we're also going to have our combination programs. We will have a readout for 279, our IL-13 and OX40 ligand head-to-head against Dupi in the second half of this year. We'll also disclose more plans on 273, which is our IL-13 TSLP combination. So a big year so far in the history of Apogee, setting us up for the next first-line launch.

Great. And before going into the details here, can you level set us by speaking to where zumi and Apogee's pipeline assets could ultimately be positioned in these markets, AD, asthma, EoE and potentially COPD? And how do you expect the AD mechanism or AD market, sorry, to evolve over the next decade, particularly with new oral agents and novel mechanisms?

Sure. Thanks for the question, Salveen. So I'll start with our monotherapy zumi for AD, right? So this will be the next first-line launch in AD. And this is a market that we believe is growing rapidly into a $50 billion market. If you look at the most recent launches, both Ebglyss and NEMLUVIO, they are just expanding the market dramatically, and we expect this to continue. We're in a market that has only about a 10% biologic penetration rate. So nothing but upside to go for zumi and AD.

I think when you look at what we're bringing to the market for this 29 launch, it's not just about dosing, although that is fundamental, you get 2 to 4 dosing days a year versus Dupixent's 26 dosing days a year. But what you get, and this is clear now through lots of different data sets, you have a highly differentiated product from an efficacy perspective. So we now have the highest absolute and placebo-adjusted efficacy across EASI-75, EASI-90, importantly, EASI-100 complete clearance as well as IGA-01, and that is both at week 16 and 52. This is a differentiated product that will sit in the first line.

I think the market will continue to develop with products that aren't showing quite the same amount of efficacy, which end up being in the second or third line. The orals that you spoke about are really important for this. And we are rooting for orals. We really want to see a and highly efficacious oral come to the market. We think that just continues to build the biologic market. You're able to then move patients, more patients more rapidly from topicals to systemics. So I think that's the way we start to see this large and growing market in AD.

As far as asthma is concerned, we are going right after Dupixent in that comorbid population of AD and asthma. Dupixent is the #1 product from a biologic perspective in asthma, and it's in spite of being fourth to market, it's in spite of every 2-week dosing -- it's because they're the only product with both indications for asthma and AD. And then as Jane spoke about, we're really excited about moving quickly forward with EoE starting this year. And we think that this is one of the largest opportunities.

If you look at what Dupixent is doing, they're doing over $3 billion a year in gross EoE sales right now. And that's only with a 5 -- excuse me, 6% to 8% biologic penetration. The reason for that low penetration is because they are taking this every week. We think that we are going to be able to bring forward an incredible opportunity for patients and physicians with quarterly or better dosing in the EoE space.

Just moving back to the Blackstone Life Sciences transaction. Walk us through the rationale for that at this juncture here? And how do the specific provisions regarding a change of control in the agreement preserve the flexibility here with regard to a potential acquisition scenario?

We were very excited to announce concurrently with the Part B data, the collaboration with Blackstone. We've been talking over a period of time of sources of capital beyond equity. We are very cognizant of dilution to our equity shareholders. So over a period of time, we've looked at what could be nondilutive for us. With the Part B data as well as the Part A maintenance in the market opportunity for zumi line launch.

And so as we were speaking with them, three topics were very important as we negotiated. One was quantum of capital; two, cost of capital; and three, strategic flexibility. On quantum of capital, I mentioned we have access up to $1.3 billion in capital, $800 million of flexibility on the royalty financing and up to $500 million on the debt. That capital with the balance sheet takes us through commercialization and potential profitability. That means we are not beholden to the equity markets.

Cost of capital, the next piece. It was very important that we look at royalty rates that were attractive from a cost point of view and that scaled down very quickly as sales grew annual sales over $5 billion and then $8 billion. It was also notable that we do not have any milestone payments back to Blackstone, which would also be a cost of capital.

And then third, strategic flexibility. It was important that terms would be frictionless from a strategic point of view. So if there would be a change of control in the future, a strategic party has the option to buy down the royalty to a low single-digit royalty rate, and that was important. What else would cause friction to a strategic? If there were any IP leans after a change of control, if there was unwieldy governance structures. So this combination of innovative terms that Blackstone worked with us on plus standard change of control terms also meant that it was frictionless. So these three key areas came together very quickly as we announced the Part B data.

And in the context of your pipeline, which is clearly poised to address multiple large market opportunities, how are you thinking about strategic partnerships to accelerate expansion into other indications or ahead of potential commercialization as well as potential M&A optionality here?

Our #1 goal is to get zumi to as many patients as possible. as quickly as possible. We wake up every day as a company thinking about how to do that and bring this to a first-line launch. We now have the capital to do that and to move quickly and to build the organization to bring zumi to launch, again, not only in AD, but as a pipeline and a product. If a strategic party can convince us that they can do it faster, bring zumi to more patients at a lower cost of capital as a public company, of course, that we would be obliged to learn.

Great. Jumping in here to the zumi atopic dermatitis data that we've seen to date. So you recently presented Phase II Part B induction data for the drug reaffirming its clinical program. Walk us through the key insights that you learned from the dose escalation data.

The objective of the Part B was to replicate the strong data that we saw in Part A. and we did that. As Jeff walked through, not only did we see robust EASI-75, both absolute and placebo adjusted. But as we look at the higher order endpoints, EASI-90, IGA-01, we also saw very robust data there. And now we're talking about EASI-100, which is completely clear skin as well as an endpoint called very low disease activity.

And so those data points confirmed the profile that we have with zumi, particularly with the mid-dose. And so we achieved the goal of the Part B, which was to replicate to do a full dose optimization study. It was important to make sure that we weren't leaving any efficacy on the table. So we did that with a higher dose. And of course, with a lower dose, we determined what was not going to be efficacious. So in our view, that trial was very successful and now sets us up to kick off Phase III trials in the second half of this year.

And one of the points of focus for investors was the improvement in outcomes on the higher order endpoints such as IGA-01 and EASI-90 at the mid-dose versus what was observed at the same dose in Part A. Just speak to Apogee's hypothesis of why this was observed.

Operationally, we've been very focused on this. And it comes down to, we think, two things. One is the larger end of the trial and also having the larger geographic footprint that resulted in seeing the activity, the efficacy on the deeper order endpoints.

And in the context of the Part A maintenance data, how should we think about the durability and depth of response over time relative to approved products?

What we saw with that continued improvement in maintenance is our conclusion on the biology, which is IL-13 is a master cytokine in atopic dermatitis. We saw that with data showing IL-13 was greater than 99% inhibited. We saw that in the skin tape data from Dr. Emma Guttman that showed not only type 2 inhibition, but also type 1and 3. And so we believe it's the combination of that master cytokine with that also breadth that resulted in what we saw of a deepening of response from week 16 to 52.

And maybe talk about the itch profile here and how that compares to what's been seen.

Yes, Salveen, that's such an important question just because of the impact of itch on patients suffering from AD. And if you look at NEMLUVIO, right, they have launched very well, and they're being marketed as an itch product, right? The lesion control is the least effective of all biologics, including Adbry. So we see how important itch is through the NEMLUVIO success.

And in Part A, we read out Part A, and we showed 48-hour itch, statistically significant itch, very similar to that of NEMLUVIO at the same time point, but in combination with TCS. And then so in Part B, what we just presented on, and we really took the focus to the 4-point itch because that's really what's going to be in the label. So the 4-point itch at 16 weeks, zumilokibart was actually stronger than NEMLUVIO with TCS and even stronger than what you see with [ JAKs ]. So we're really excited about that because what it does is it prevents physicians from having to choose between either managing itch or managing lesions. And in fact, with zumi, they have the ability to manage both.

And maybe talk about the APEX study in the context of enrolling a slightly less severe population versus the Phase III trials for Dupixent and EPLI. How should we interpret the results in that context?

Yes, it's a good question. I think -- so the days of baseline 30s are gone, right, with a few products on the market. But I think importantly, if you look at our results from both Part A and Part B, they tell the same story, which is to say the more severe patients do at least as well, if not better on zumilokibart. So we feel very confident in zumi's ability to manage both that less than 21 and greater than 21 more severe patient population.

As we look to the Phase III here, speak to the study design here and Apogee's confidence in replicating the Part B data.

So as we look at the Phase III for zumi that we're going to kick off the second half of this year, it follows a pretty standard path that we've seen for AD, and that is to replicate trials. It will be 400 patients each of zumi versus placebo. And then important for the label, a third trial in combination with TCS. Based on what we did with Part B replicating the success of Part A, we plan to have a very similar geographic footprint, similar criteria. And based on that, we have very high conviction in the ability to replicate in Phase III the success that we've seen in APEX Phase II.

And how are you mitigating the potential for a high placebo response rate, which has been seen in recent atopic dermatitis trials?

A key part of that is the geographic footprint. And so we will do that for the Phase III. I think what we're seeing a leveling out for EASI-75 is about a 20% placebo rate. But then when you look at the higher order endpoints, which are harder with the placebo, you can see those rates coming down. So all the operational things that we did in our Phase II trials in terms of site selection, in terms of derm specialty, in terms of, again, the geographic footprint, we think all of that will lead to a good outcome on the placebo side.

And is the goal to get a label with both every 3 months and every 6-month dosing? And how do you see that playing out commercially? What type of patients will be best suited for 3 months versus 6 months? And maybe also speak to physician willingness to put a 6-month therapy in a patient?

Yes, it's a great question. So first of all, the goal and the expectation is that we will have both every 3 and every 6 months on the label. So that's the expectation. I think if you look at the 52-week data, you see maintenance of response was similar and both incredibly strong with both Q3 and Q6 months. physicians and patients really both are telling us that they want optionality, and we want to give them optionality, and we have the ability to do so. I think when you do market research with physicians, it's split sort of evenly as to if they would prefer every 3 or every 6 months. And I think both are going to be transformative, right?

The Q3 month alone is going to help us to be able to dive much deeper into biologic penetration, pulling more patients from topicals over. But we think Q 6 months as we talk to patients, is going to be even further helping us to move patients to biologics. I think the way it plays out is we -- first, we want physicians and patients to use it however they'd like. I think the way it plays out is you're likely going to get a lot of physicians that want to get comfortable on 3 months.

Keep in mind, they're only going to have 4 dosing days in induction versus the competitors at 9. So those 4 dosing days, I think you'll get a lot that move straight to Q3 months and then slide over. We do hear some that would prefer to just start at Q6 months. They're getting some repetition in that in asthma, for example. So they're getting more comfortable with it.

And interesting, Salveen, is when you talk to physicians and ask them what the 6 months will do, 92% of physicians have told us that in market research that with the addition of Q6 months, they will continue to increase above and beyond the high percentage that they're going to use for zumi already. So we think that it's important to the market, and it will continue to drive more and more patients to zumi.

And the rate of conjunctivitis seen with zumi has been consistent with the broader. What would you think is an acceptable rate for conjunctivitis and antidrug antibodies in a Phase III?

With Dupi and lebri, we've seen a rate of about 14% to 30%. So we would need to be within that range. For our Part B mid-dose, our pool conjunctivitis rate was 10%. On ADAs, we continue to see no impact of ADAs on PK, on efficacy or on safety.

Great. Looking ahead, can you discuss the market access strategy for zumi at the time of launch, noting it will enter a market with other branded agents? How will positioning evolve as biosimilars for Dupixent enter the market potentially as early as 2031? And walk through the economics of why PBMs could favor branded agents such as zumi in the frontline setting versus someone who has an established presence or multiple drugs in their portfolio?

Yes, it's an important question. So first, I would say our market access strategy is to have early frontline access, and we're already starting this strategy. We're in front of payers already. And that is our expectation, early frontline access. If you look at both Ebglyss and NEMLUVIO, very small differentiation to Dupixent, both have frontline access, meaning they do not have to step through Dupixent nor will we. I think when you look at a product that is going to be used in high demand, payers see the value of extended dosing options in the I&I space.

Obviously, if you look at something like a Skyrizi, 40-plus percent market share in plaque psoriasis, they know that physicians and patients will want this. So they have to find a way to have access and have this on the formulary. Otherwise, what will happen is every time a product is used, they will pay full list price. They will not have rebates, admin fees, data fees, they will not get enterprise fees. All of that goes away. So we have a high level of confidence for early first-line access.

I think to your question on how this changes with biosimilars, I would say that it doesn't change anything for zumi. So a biosimilar Dupixent, for example, in time will not have an impact on zumi. What happens is -- and you can see this across other disease states, what happens is when a product goes biosimilar, that product is the product impacted, not the products around it in the I&I and biologics space. And I think there's a misunderstanding on this topic in the investment community.

For example, you look at STELARA in 2025, it goes biosimilar. So when a STELARA prescription is written, the payer will force a much less expensive biosimilar STELARA. But what you do not see is any product around that having an impact, a negative impact to access, not in '25, not in '26. Why is that? Simply put, it's because if a payer were to force other branded biologics through a biosimilar their contract becomes null and void. So they no longer then pay the rebates, admin fees.

And when you look at AD specifically, you have Dupixent with the lion's share of market. And if you look at their 2-year rate, they have a discontinuation rate of about 50%. Those patients are not just cured from atopic dermatitis, they end up on other products. And as they move to other products, if the payer does not give access to those other products, they're paying full price. And when they do that, it negatively impacts their financials. It increases the cost of the entire class of products, which changes what everyone pays for insurance. So it does not work for them, and that's why you don't see that elsewhere, and that's why we will not have an impact from a biosimilar Dupixent.

Moving to the respiratory side. So Apogee is advancing the drug into a Phase IIb study in moderate to severe asthma patients, which you noted could be potentially registrational. What needs to be achieved for you to be able to file on this? And you're evaluating an annual dose here in Phase IIb. Could you speak to that choice and what supports a different dosing schedule here versus our strategy versus AD?

So we announced the IIb plans, a 500-patient trial. We are going to, given the biology, enrich for EOS greater than 150 as well as exacerbation history. There's good precedents from and the respiratory division of the FDA that a IIb can be registrational, and that is with a 500-patient study. We're building this trial off of the very good data that we saw in our Ib trial for zumi in asthma, which we reported earlier this year, which we showed durable FeNO suppression out to 8 months. FeNO is an accepted biomarker in the asthma space.

And so building on that data, building on the data that we've now seen for zumi overall, we've designed the trial to include, as you noted, 3-month, 6-month and 12-month dosing. Based on what we know of the PK, based on what we know of IL-13 and asthma, we think it makes sense and it's logical and with where the field is going to not only test 3 and 6 months, but also to see what it looks like on a 12-month basis as well.

And speaking of TEZSPIRE, so you are going to advance your drug 273, the IL-13 plus TSLP in respiratory indications here, asthma and COPD with trial plans to be announced in the second half. Outline the areas of potential differentiation from the other TSLP targeting agents and such as Sanofi's and Genmab's drugs.

So for Lunsekimig, we think...

[indiscernible] sorry.

I know what you meant. For Lunsekimig, which is given monthly, we clearly could see our 273, our IL-13 and TSLP have a dosing advantage. The other opportunity by the combination of the 2 mechanisms is reaching a broader patient population. With a T2 targeting antibody like IL-13, you're looking at the EOs greater than 150. By combining it with TSLP, we think we could get breadth of patients as well as exploring higher efficacy. And so whether it's Lunsekimig on the dosing or generates TSLEP mono, those breasts and seeing how we can push on the efficacy ceiling.

Great. And on the EoE side, what would you need to see in the Phase IIa proof-of-concept trial to take this into registrational studies or to establish proof of concept?

Yes. This is an open-label trial. We're going to enroll 30 to 50 patients. The primary endpoint is histology, it's eosinophil count as well as look at patient diaries as well as endoscopy. And so you can't have a placebo effect on histology, eosinophil count. So we believe that data will help us then design the next trial. It is potentially one that could be one of the most exciting. We hear from patients and docs all the time. Our patients don't like taking Dupi every week. It is a painful injection. Please see if you can come up with something monthly. And we are, of course, working on something that could be every 3 or 6 months. So as Jeff outlined earlier, it is a large indication, the third largest for Dupi between AD, asthma and EoE that represents over 75% of Dupi sales. So a very, very important indication.

Great. And your 279 drug here, with first data expected this year, what is the target profile of your IL-13 OX40 co-formulation in moderate to severe AD? And also speak to the rationale here of moving forward with this in the context of 2 large players ending their OX40 trials post Phase III data?

I'll start first on what's the bar. The zumi data for Part A and Part B has raised the bar for 279, frankly. And so as we look at that head-to-head Dupi, which reads out the second half of this year, points higher than efficacy than just zumi, which translates into north of 15 points better than Dupi. So a high bar, a high bar means from a capital allocation point of view that if it does not meet that bar, we will not take it forward.

Great. Jeff, do you want to add anything from a market point of view and from the second line?

Yes. From a market perspective, if we are able to increase efficacy by that 10 points that Jane is speaking of, this becomes the second-line product of choice, and it pushes JAKs back. So why is that? You're going to get JAK-like efficacy with a co-formulated combination biologic that is much safer than JAK. So when you look at the JAK profile and the multiple black box warnings and so many things that dermatologists cannot control, deep vein thrombosis, for example. These are things that concern derms and physicians versus the ability to do skin checks for [ Cosi ] much, much safer product, and you're going to get that same sort of efficacy. So it becomes the second-line drug of choice if we're able to deliver that.

Great. Well, with that, any last things that you want to highlight given the extensive portfolio here?

It's been a really important 6 months for Apogee, probably the most important in our history. And the team is very excited to bring this to Phase III, bring this to launch and answer the ask by physicians, which is please bring it to the market as quickly as possible. And we're really happy to have the capital now to do so without any need for equity and to also bring the pipeline and the product opportunities forward as well.

Great. Well with that, Jane and Jeff, thank you so much.

Thank you, Salveen. We really appreciate the discussion.

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 now 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, 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 B initial 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 our current treatment gaps in atopic dermatitis, followed by an overview of our zumilokibart development program by Kristine Nograles, SVP, Head of Clinical Development and Medical Affairs for Dermatology; and Amol Kamboj, SVP, Head of Clinical Development for Respiratory and GI. Lastly, Michael will summarize our vision for building a leading I&I company and the anticipated future milestones for zumilokibart as we advance its development. The subsequent Q&A will be led by Michael, Carl; Apogee's Chief Financial Officer, 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. Today is a big day for Apogee. We are thrilled to share positive Part B results that give us a clear path to Phase III later this year with data that we believe will be incredibly exciting for patients and the dermatology community. In addition, today, we announced a concurrent strategic financing collaboration with Blackstone Life Sciences, which when combined with our strong existing balance sheet, will allow us to commercialize zumi in atopic derm, asthma and eosinophilic esophagitis without needing to rely on equity capital markets.

Taking a step back, Apogee was founded with a goal to transform standard of care for atopic derm and other type 2 inflammatory conditions. AD is the largest and fastest-growing I&I market, projected to reach over $50 billion, yet treatment options are limited with significant efficacy benefit left on the table and onerous 2- to 4-week dosing required. Today, we will share new data from Part B, the dose-ranging component of our APEX Phase II trial, which continues to support zumi's potentially transformative profile in AD. Zumi demonstrated robust clinical activity across all lesional and itch endpoints at week 16. Importantly, previously disclosed Part A 52-week data showed that zumi's clinical activity continues to improve beyond week 16, with dosing just 2 to 4 days per year in maintenance required. If approved, this could be the first product in any dermatologic indication to offer the option for every 3- or 6-month dosing.

With today's data and the bespoke capital facility provided by Blackstone, we believe Apogee has a path to commercialization and profitability. We are thankful to the patients and physicians that have enabled us to share this with you today.

With today's positive data from APEX Part B, we have achieved our objective of identifying a dose regimen that we believe maximizes the potential of IL-13 inhibition in atopic derm. In this trial, evaluating low, mid and high doses of zumi versus placebo, we observed similar clinical activity with both the mid and high doses. The low-dose arm achieved relatively lower clinical activity as expected. With this data, we are well positioned to engage regulators with our plan to take forward mid-dose zumi to Phase III, which is an optimized dose that demonstrated robust clinical activity across all lesional and itch endpoints, a well-tolerated safety profile and substantially reduced injection burden versus standard of care.

Zumi mid-dose was highly stat sig versus placebo across all endpoints tested. Notably, a meaningful proportion of patients treated with mid-dose zumi achieved EASI-100 or completely clear skin at 16 weeks. Overall, we believe zumi's profile has the potential to set a new standard of care in atopic derm.

We have a unique opportunity with zumi to potentially transform the future $50 billion AD market. We previously shared data from APEX Part A showing that 2/3 of patients treated with zumi achieved an EASI-75 response at week 16 and that these responses were maintained with as few as 2 to 4 dosing days per year in maintenance. Today's 16-week data from APEX Part B was remarkably consistent with Part A, providing further evidence that zumi could be the frontline drug of choice in AD.

Across all lesional and itch endpoints tested in APEX Part B, zumi demonstrated a highly competitive profile at week 16 on both an absolute and placebo-adjusted basis. Together with data shared earlier this year, showing responses continue to improve after week 16 with maintenance dosing of just 2 to 4 days per year, we believe zumi clearly has potential to improve upon standard of care.

I will now hand the call over to Carl, our Chief Medical Officer, to walk us through today's data in more detail.

Thank you, Michael. I'm excited to share the zumilokibart APEX Part B trial results with you all today. In the APEX Part B trial, the modified ITT population consisted of 346 patients that were randomized 1:1:1:1 in the induction stage to receive either a low, mid or high-dose regimen of zumilokibart or placebo. The study was designed to determine the dose of zumilokibart that enables the strongest clinical activity while maintaining a safety profile consistent with the IL-13 class and minimizing injection burden. Our goal was to fully explore the dose response of zumilokibart and ensure we did not leave any efficacy on the table, which we feel we have achieved with the study results being presented today.

As Michael has noted, with today's results, the mid-dose from the study is the planned Phase III dose pending regulatory interactions. I'll focus today's discussion on the results at week 16, but the study is designed such that all patients are re-randomized into either the 3- or 6-month dosing arms in the maintenance portion of the study, which we'll plan to release next year. As a reminder, zumilokibart's planned Phase III induction regimen requires just 4 dosing days compared to 9 for dupilumab, representing a more than 50% decrease in the injection days during induction. Part A 52-week results shared earlier this year demonstrated zumilokibart's potential to reduce injection burden during maintenance even further with just 2 to 4 dosing days per year compared to 26 for dupilumab, and up to 13-fold decrease in the injection burden for patients with moderate to severe atopic dermatitis.

Baseline characteristics and demographics of participants in this trial were generally well balanced and in line with expectations. The severity of patients enrolled in APEX Part B increased from APEX Part A and is aligned with contemporary trials. Zumilokibart was well tolerated. Results were consistent with expectations for the IL-13 class. Adverse events that occurred in 5% or more of patients in one or more zumilokibart treatment arms included nasopharyngitis, headache, non-infective conjunctivitis, upper respiratory tract infection, dermatitis atopic and urinary tract infection.

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. Rates of conjunctivitis across treatment arms were generally in line with standard of care. For the planned Phase III zumilokibart dose, the non-infective conjunctivitis rate was 5.9% and the pooled rate across all conjunctivitis-related preferred terms was 10.6%. There was no effect of ADAs on PK clinical activity or safety.

APEX Part B met the primary endpoint of the study, which was EASI-75 response at week 16 with significance achieved for all zumilokibart treatment arms starting at week 2. Zumilokibart mid- and high-dose arms demonstrated comparable activity with 65.9% and 61.6% of patients achieving EASI-75 at week 16, respectively. As expected, zumilokibart low dose showed relatively lower clinical activity with 50.5% achieving EASI-75 at week 16. The mid and high doses of zumilokibart replicated the results previously seen in APEX Part A on both an absolute and placebo-adjusted basis, APEX Part A and Part B mid-dose results were within 1 percentage point.

When we look at the more sensitive continuous endpoint of percent change from baseline in EASI score, the trend across treatment arms is consistent with EASI-75 with zumilokibart mid- and high dose showing comparable clinical activity and low dose showing relatively lower clinical activity. Importantly, zumilokibart mid-dose showed a rapid effect on lesions, achieving significance as early as week 1. As with EASI-75, the mid and high doses of zumilokibart replicated the results previously seen in APEX Part A here within 2 percentage points on both an absolute and placebo-adjusted basis.

Moving to the more stringent secondary endpoint of IGA 0/1, which will be part of the co-primary endpoint of EASI-75 for the Phase III trials of zumilokibart. Zumilokibart mid-dose demonstrated robust clinical activity with 46% of patients achieving IGA 0/1 at week 16. Zumilokibart high dose generally trended similar over the 16-week period. As expected, zumilokibart low dose showed relatively lower clinical activity. As expected, EASI-90 showed a similar trend as IGA 0/1 with 47.4% of patients treated with zumilokibart mid-dose achieving EASI-90 at week 16.

We also saw deep itch relief. Over half of patients, 50.5% to be exact, treated with zumilokibart mid-dose achieved a 4-point or greater reduction from baseline on the itch numeric rating scale at week 16 with zumilokibart high dose generally trending similar over the 16-week period. As expected and consistent with regional endpoints, zumilokibart low dose showed relatively lower clinical activity. The APEX Part B results showcase zumilokibart's competitive profile in atopic dermatitis. The zumilokibart planned Phase III dose demonstrated an absolute EASI-75 at week 16 of 65.9% and a placebo-adjusted delta of 41.9%. These results compare favorably with standard of care and the non-head-to-head trial comparisons are shown on the right for all approved biologics.

Zumilokibart mid-dose also demonstrated a competitive profile for the more stringent endpoint of IGA 0/1 with the zumilokibart planned Phase III dose demonstrating an absolute IGA 0/1 at week 16 of 46% and a placebo-adjusted delta of 34.8%. Non-head-to-head comparisons for all approved biologics are again shown on the right. Similar to IGA 0/1, zumilokibart mid-dose also compared favorably on the more stringent endpoint of EASI-90 with the zumilokibart planned Phase III dose demonstrating an absolute EASI-90 at week 16 of 47.4% and a placebo-adjusted delta of 37.8%. Non-head-to-head comparisons for all approved biologics are again shown on the right.

Similar to lesional endpoints, zumilokibart mid-dose demonstrated competitive itch improvement at week 16. The itch improvement seen by zumilokibart compares favorably to standard of care in non-head-to-head trial comparisons shown on the right, including nemolizumab in combination with topical corticosteroids. Specifically, the zumilokibart planned Phase III dose demonstrated an itch response of 4 points or greater at in 50.5% of patients and resulted in a placebo-adjusted delta of 36.7%.

Prior clinical trials for biologics in atopic dermatitis generally have not reported data for EASI-100 responses, which represent completely clear skin, or composite endpoints, which represent the simultaneous control of lesions and itch for patients with atopic dermatitis. While comparable data is not available for lebrikizumab, nemolizumab or [ tralopinumab ], these 2 endpoints are available from a head-to-head trial of the JAK inhibitor upadacitinib versus dupilumab called [ LEVELUP ]. [ LEVELUP ] was the first and only study to use a composite endpoint of EASI-90 and itch NRS of [ 001 ] as a primary endpoint, which is an endpoint classified as showing very low disease activity or VLDA.

In this study, upadacitinib showed EASI-100 and VLDA rates that were 2 to 3x higher than dupilumab. For each of these endpoints, we have added zumilokibart's APEX Part B data as a non-head-to-head comparison to the left of the [ LEVELUP ] data. For EASI-100, the zumilokibart planned Phase III dose demonstrated a 16.5% absolute response and a 13% placebo-adjusted delta. Additionally, 20.6% of patients achieved very low disease activity measured by the composite endpoint of EASI-90 and itch NRS of 0 or 1. These results demonstrate the depth of response being seen after 16 weeks of treatment with zumilokibart.

Overall, we couldn't be more thrilled with the study results and the profile of zumilokibart, which provides robust lesion control with reduced injection burden for patients.

Before we discuss what is next for zumilokibart, we are pleased to have Dr. Ruth Ann Vleugels of Mass General Brigham Department of Dermatology here on the line with us to discuss treatment gaps in atopic dermatitis. Dr. Vleugels is an expert in inflammatory skin diseases, a Professor of Dermatology at Harvard Medical School and the Director of the Atopic Dermatitis Program at Mass General Brigham Hospital, among her many credentials. Thank you so much for being with us today, Dr. Vleugels.

Thank you so much for that kind introduction, Carl. I really appreciate it. And I'm actually delighted to be here to speak with you all today about treatment gaps in atopic dermatitis because this is an area that I'm extremely passionate about. Atopic dermatitis is actually our most common inflammatory skin disease. It affects infants, it affects the elderly and everyone in between. And I'm sure that you can see by looking at this gentleman in the photo that this is profoundly impactful on our patient's quality of life.

When I'm teaching medical students at Harvard Medical School, I often try to explain this by saying, imagine you had a couple of hundred of mosquito bites or poison ivy over your entire body and then imagine that, that goes on for years because this rash and itch is really a severe and systemic problem for our patients that profoundly impacts their quality of life.

So let's think about how it does so. So because of this intense itch, patients really lose sleep, adults often miss work, children often miss school. In addition, we have excellent data in children to show that pediatric patients actually have growth restriction. So our kids with atopic dermatitis don't reach their full growth potential because of their atopic dermatitis. Adults have reduced physical activity, and we know that we see increased mood disorders in patients with atopic dermatitis, in particular, depression. In addition, patients have many specialist visits. They often have increased hospitalizations, and we actually even see increased skin infections in patients with atopic dermatitis as well. So you can ideally see that this is really a multifactorial impact on quality of life from this severe skin disease.

So we do have advanced treatments for atopic dermatitis that have improved the quality of life for our patients. But before we think about this, prior to 2017, it's important to level set that we primarily use topical therapies and dermatologists often would reach for systemic corticosteroids. Now we know systemic corticosteroids have many side effects that are highly impactful for patients. They cause diabetes, weight gain, high blood pressure, bone damage, et cetera. And so our Academy of Dermatology actually recommends against their use in this disease. So since 2017, we have these therapies, 3 approved biologics as well as 2 oral approved JAK inhibitors. So dupilumab and lebrikizumab are the biologics in the IL-4 and IL-13 family. Both of these medications have improvement in lesions and also itch.

Now a key thing when we're thinking about these medications is that they are administered by self-injection and the frequency for these is between every 2 to 4 weeks. So patients have to inject up to 26 times a year, which is a challenge for many of our patients. Nemolizumab is an anti-IL-31 medication. This is a medication that's known to have rapid itch relief. However, it does have limited improvement in rash. And so that is a limitation of this medication. In addition, it is still dosed by self-injection every 4 weeks. Our oral JAK inhibitors, upadacitinib and abrocitinib, do have rapid onset of action and could help both lesions and itch. These are oral medications that are dosed daily. And in addition, all JAK inhibitors carry a boxed warning for blood clots, major cardiac events in cancer. And this box warning is the primary reason why JAK inhibitors have faced practical limitations in their widespread adoption for atopic dermatitis.

So when I'm seeing patients in my atopic dermatitis program, it's very clear that our patients are looking for improved treatment options. And really, what they want is impressive efficacy with a clean safety profile. And this is really important because the zumilokibart data not only shows that zumilokibart has numerically improved endpoints than all existing biologics. But in addition, the efficacy is numerically similar to JAK inhibitors at week 16, including on our highest threshold endpoints. And these include very low disease activity as well as EASI-100. And it's important to remind ourselves that EASI-100 is completely clear skin. And so until now, this is really an endpoint that we aren't used to thinking about when we talk about biologic therapies.

In addition, we know that after week 16, responses in zumilokibart-treated patients actually improved and actually over 40% of patients achieved completely clear skin on every 3-month dosing by week 52. So again, this is just a really robust endpoint, and this really is what our patients are looking for. And this efficacy is in conjunction with safety data that is comparable to our other IL-4 and 13 medications. And this is extremely important because we know that in the dermatology world, both our patients and my colleagues really are making their decision-making about therapies primarily based on safety. And we know that the IL-4, IL-13 class is a class that they feel extremely comfortable with. So in conjunction with this impressive efficacy data and this clean safety profile, we also need to think about the injection burden because, as I mentioned, this can be a challenge for many of our patients.

So in the induction period, zumilokibart needs 4 dosing days. So this is over a 50% reduction from existing biologic therapies. In addition, when we look at the maintenance data, zumilokibart patients would need 2 to 4 injections per year. So that's actually 22 to 24 fewer shots than the current standard of care therapy in atopic dermatitis. So a highly meaningful difference for our patients in terms of that overall injection burden. So from this data, we can really see that zumilokibart could address several unmet needs in atopic dermatitis because although we do have newer therapies that have greatly improved the lives of our patients, there's still substantial unmet need for a highly efficacious therapy that has a safe profile, but also reduced injection burden.

So the key takeaways for me is that zumilokibart was not only well tolerated in patients, but in addition, the safety profile is in line with that of the IL-4 and IL-13 class. And again, this is a class that we know my colleagues feel extremely comfortable with because of this clean safety profile. In addition, the data we saw today demonstrates that zumilokibart has efficacy that's numerically similar to JAK inhibitors, which is really a bar that we've been reaching for and that previously we haven't seen from a biologic medication. So this is highly meaningful. In addition, the itch data is numerically similar to nemolizumab, which is the biologic that we consider to have the highest efficacy for itch. So again, this will be extremely meaningful not only to patients but also to my dermatology colleagues.

From previously presented data, we also know that zumilokibart shows improved responses over time and that even with dosing as infrequent as every 3 to 6 months, we have high efficacy, which will allow our patients to have excellent outcomes, but also not to have frequent injections, which is something our patients are really asking for in the clinic on a regular basis. Together, this strong efficacy and safety data, coupled with an extremely meaningful reduction in injection burden highlights that zumilokibart is poised to become the biologic of choice for patients with atopic dermatitis.

Thank you so much for your interest in our patients with atopic dermatitis.

Thanks, Dr. Vleugels, for highlighting the treatment gaps in atopic dermatitis and the potential for zumilokibart to address these unmet needs.

The exciting results from Part B have now enabled us to select the dosing regimen for our Phase III program, which we plan to initiate in the second half of this year, pending regulatory alignment. The [ ADVENTURE ] Phase III program for zumilokibart will include 3 clinical trials, beginning with the [ ADVENTURE ] 1 and 2 monotherapy studies each of which is expected to enroll approximately 400 patients with moderate to severe AD.

During the induction phase, patients will be randomized to receive either mid-dose zumi or placebo. Patients will then transition into the maintenance phase where we will continue to evaluate both 3- and 6-month maintenance regimens. The trial design will be very similar to Part B with respect to the patient population and geographic footprint, and the studies will evaluate EASI-75 and IGA 0/1 as co-primary endpoints, both of which were robustly assessed in our Phase II study.

The third trial in our Phase III program is the [ ADVENTURE-TCS ] trial, which will evaluate zumilokibart in combination with topical corticosteroids. [ ADVENTURE-TCS ] is also expected to enroll approximately 400 patients who will be randomized to receive either mid-dose zumi or placebo, both in combination with topical corticosteroids. During the maintenance phase, we will evaluate every 3 months maintenance dosing of zumi and TCS.

As with the monotherapy studies, [ ADVENTURE-TCS ] will be very similar to Part B in terms of the patient population and geographic footprint. EASI-75 and IGA 0/1 will also serve as the co-primary endpoints in this study. We are very excited to initiate the Phase III program for zumilokibart planned in the second half of this year and incredibly grateful to the patients, investigators and site staff who have participated in our AD trials to date. Their partnership and commitment have been instrumental in advancing our clinical development program in atopic dermatitis.

And with that, I'll now turn the call over to Amol, who will discuss our development plans for zumilokibart beyond AD.

Thank you, Kristine, and good morning, everybody. I'm pleased to join today's call to provide a closer look into our plans for zumilokibart beyond atopic dermatitis. We are excited to evaluate its pipeline and a product potential across multiple I&I indications, starting with Phase II programs for asthma and eosinophilic esophagitis, or EoE, both of which we expect to initiate over the coming quarters.

We know that patients very often suffer with multiple type 2 inflammatory conditions. For example, an estimated 25% of patients with atopic dermatitis and 40% of patients with EoE have comorbid asthma. As an allergist, I've seen how debilitating these conditions can be and especially so for patients suffering with more than one. The potential for zumi to treat a broad spectrum of type 2 inflammatory disorders could transform standard of care for these patients. We've now twice seen what zumilokibart may offer for patients with atopic dermatitis. We're incredibly excited about zumi's potential in asthma and EoE as well. And beyond these conditions, zumi has potential in other dermatologic, respiratory and GI indications with the potential for a straight to Phase III approach using optimized Phase IIb dosing regimens in each of these therapeutic areas.

Following this year's positive Phase Ib asthma readout, where a single dose of zumilokibart drove deep sustained phenosuppression for up to 32 weeks, we plan to initiate the ASPIRE Phase IIb trial enrolling patients with moderate to severe asthma. This randomized placebo-controlled study will include patients with elevated type 2 biomarkers and a history of exacerbation in the prior year and is designed to be registrational. Participants will be randomized to 1 of 3 zumilokibart arms in every 3, 6 or 12-month dosing regimen or placebo. The primary endpoint will be annualized exacerbation rate at week 52. We plan to initiate the ASPIRE trial in the first quarter of next year.

ELEVATE is our Phase IIa proof-of-concept study in eosinophilic esophagitis, which we also plan to initiate in the coming quarters. This study will enroll 30 to 50 patients who will receive a zumilokibart induction regimen followed by a maintenance treatment period testing both every 3- and 6-month dosing as we've done in atopic dermatitis. The primary endpoint of the trial is histologic improvement as assessed by eosinophil counts. We will also be assessing endoscopic change and patient symptoms.

Our plans to launch the ASPIRE and ELEVATE trials over the coming quarters underscores zumilokibart's potential to redefine the treatment paradigm across type 2 inflammatory disorders. Zumi could become the first long-acting biologic approved for both atopic dermatitis and asthma. Currently, only DUPIXENT dosed every 2 weeks is approved for both indications. It is also the most commonly prescribed biologic in both AD and asthma. We recognize that DUPIXENT being approved in both indications is an important driver of this, given the opportunity to treat patients suffering with both conditions.

In EoE, zumi has the potential to be dosed just 2 to 4 times per year. As a reminder, DUPIXENT is the only biologic approved in EoE and is dosed weekly in this indication. That's 52 injections per year. Imagine how transformative 2 to 4 annual injections would be for patients and families living with EoE. On the heels of the exciting atopic dermatitis data that Carl presented earlier, the initiation of these 2 important studies is the next step in exploring zumi's potential to deliver a best-in-class profile across type 2 inflammatory diseases, and we're excited for these next steps.

I will now pass the call back over to Michael for closing remarks.

Thank you, Amol. Atopic derm is the largest and fastest-growing I&I market with DUPIXENT's launch outpacing the entire $25 billion plaque psoriasis market. New entrants with limited differentiation are quickly becoming blockbusters in their own right, while DUPIXENT continues to grow rapidly, speaking to the unmet need and significant underpenetration of this market. Zumi's anticipated launch in 2029 could be the next meaningful frontline launch for this population.

Taking a step back, 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 3 areas that patients and physicians tell us are in most need of innovation where current biologics come up short. Zumi delivered against all 3, and we are confident in its potential to be the next clearly differentiated first-line product to launch in atopic derm. In today's APEX Part B readout, zumi demonstrated robust clinical activity at week 16. And we know from maintenance data shared earlier this year that patients continue to improve after week 16 with 41% of patients achieving EASI-100 at week 52, representing completely clear skin. It's clear that zumi could be a transformative therapy for atopic derm patients with just 2 to 4 dosing days per year in maintenance compared to 26 injections per year for standard of care, which has not demonstrated improved responses after week 16.

Today, we also announced a major strategic financing collaboration with Blackstone, a trusted partner to our industry who shares our conviction in zumi's potential to transform standard of care for patients living with type 2 inflammatory conditions. Our partnership with Blackstone provides up to $1.3 billion in additional capital, significantly bolstering the financial resources we can deploy to develop and deliver zumi for as many patients as we can as quickly as possible, including today's announced Phase III development program in atopic derm. The customized structure matches cash flow to Apogee's future funding needs at a competitive cost of capital and without equity dilution to our shareholders. We are pleased to have found the right partner in Blackstone to help realize our expansive vision for zumi.

With an exciting 2026 for Apogee well underway, we wanted to wrap up today's call with a look ahead to the coming years, which includes multiple expected value-creating catalysts for zumi through 2028, including additional data in atopic derm and eosinophilic esophagitis next year. In addition to our lead program, we are advancing multiple innovative combination programs, which have the potential to raise the bar over monotherapy. We are looking forward to sharing more details on these programs later this year.

I will now hand the call back over to the operator to begin Q&A. Thank you.

[Operator Instructions] We will take our first question from the line of Tyler Van Buren from TD Cowen.

Congratulations on the data, and thanks for the presentation. Considering that the mid-dose induction data improved in Part B compared to Part A on the higher order endpoints, can you and perhaps Dr. Vleugels elaborate on the importance of EASI-90, EASI-100 and IGA 0/1 in the treatment of atopic dermatitis today and the focus on these endpoints among KOLs and patients? And just as a follow-up or a second question, forgive me, but can you also just elaborate on why you felt the need to do the Blackstone deal now?

Thanks, Tyler. I appreciate the question. I'll hand it off to Carl and Dr. Vleugels for the first and then we'll circle back on the second.

Yes. Thanks so much for the question. Obviously, we were really excited to see the improvement, especially on deeper endpoints here. I think part of the key trial design here in doing a Part A and Part B is that we designed the Part B to most clearly represent what we would go forward with in terms of our Phase III program. So it's a bigger study, a more global footprint, and we think that's really important in terms of the replicability of our Part B data to our Phase III program overall. That also -- just the size of the study also gave us more power on these deeper endpoints like EASI-90 IGA 0/1 and EASI-100 as well as itch NRS of 4 among other pieces. And that's why I think we're seeing really the true effect of zumilokibart in the mid-dose Part B data.

But really to contextualize that, obviously, Dr. Vleugels is much better in terms of that piece. So I'll turn it over to her to discuss the meaningfulness of these endpoints and what she's seeing with zumilokibart.

Yes. Thank you for this important question. I really appreciate it. So maybe just to level set in clinic, when we're prescribing medications for patients with atopic dermatitis, even the substantial number of decreased injections would be a dramatic shift in atopic derm market, but the enhanced efficacy based on these higher order endpoints that you mentioned is actually what is even more impressive.

And so to kind of describe that, essentially, when we look at EASI-90 or IGA 0/1, the fact that these are essentially 10% to 15% numerically higher than the other biologics in the market is highly meaningful to us because these are the endpoints that our patients would really like to dramatically improve their quality of life. And as I mentioned in my brief comments, we've really been looking for years for essentially a biologic that would approach or equal JAK-like efficacy, but have the safety profile of a biologic because dermatologists more than pretty much any other field I worked for, we're driven by safety field. So the fact that we have this JAK-like efficacy from a biologic is highly impactful.

And to comment on that, the EASI-100 actually hasn't been reported in any biologic Phase III study. Like this isn't something that we would even expect to track. And the fact that in the 52-week data, we have nearly half of patients meeting EASI-100, that is sort of more than I could have even dumped up when these trials started. And I think in speaking with my colleagues about these higher order endpoints, these are really exciting to my colleagues. And when we think of this ability, these are the types of therapies we actually start talking to patients about in clinic even prior to their approval. like this is coming, keep this in mind. And the reason for that is because patients are really sick of doing their frequent injections, and they're also looking for therapies that can have improved efficacy.

So here, we're sort of able to see that on both sides. So this is something my colleagues will really be looking forward to.

Thank you, Dr. Vleugels. And on the second question, Tyler, about why the transaction with Blackstone now, I think it was important to us in our discussions with them, right? We felt that they were a great partner that provided us a bespoke capital structure and an attractive cost of capital that gives us a path to commercialization and even profitability without needing to rely on the equity markets anymore. I think that was something we had heard from investors in the past, right, how will you fund this through launch and even profitability. And we have that now.

And I think what was also quite essential was that we maximized coming out of this data set, our strategic optionality and flexibility. And they met us where we were on that. And I encourage folks to read the 8-K where you can see that upon -- there are specific provisions around change of control, et cetera, including within the first 180 days that give us an ability to buy down that royalty to quite an attractive low single-digit rate as well. So it was kind of a no-brainer from us because it gives us a clear path forward while keeping all optionality clearly on the table.

The next question comes from Seamus Fernandez from Guggenheim.

So 2 questions. Can you guys talk a little bit about the strength of the EASI-90 data and the IGA 0/1. That seems quite a bit more consistent with the data in this data set than perhaps what was perceived in Part A. So just hoping you could maybe put a finer point on the importance of those endpoints. And then with regard to the conjunctivitis, maybe just help us understand also from the physician's perspective, the non-infective conjunctivitis frequency versus the overall conjunctivitis and the potential impact of ascertainment bias as people seek to compare across data sets.

Great. Thanks, Seamus. Yes, I'll hand it to Carl and then, of course, welcome Dr. Vleugels input as well on these 2 questions.

Yes. Thanks so much, right? I think that you're really pointing out, I think, something important in this data set to, one, as we mentioned in the presentation, really good replicability of the EASI-75 endpoint and percent change from baseline in EASI. That was really what Part A was designed around with those kind of 2 endpoints based on kind of the size as well as the geographic footprint, and we really replicated those with high fidelity here. But in Part A, saw a very competitive EASI-90 and IGA 0/1, but maybe didn't see that we were getting something more with the additional exposures that the mid-dose has, right? As a reminder, even the mid-dose has 30% to 40% greater exposures compared to lebrikizumab. And really in the first 4 to 6 weeks, it's actually more like 50% to 60% greater exposures compared to lebrikizumab. We really felt like in Part A, we tapped into that in terms of the greater than 40% placebo-adjusted delta on EASI-75 but maybe didn't see what we expected in terms of the deeper endpoints.

Here with a bigger study, more global footprint, I think we've tapped into that greater exposure driving these deeper endpoints of EASI-90 and IGA 0/1, both well above 30% on a placebo-adjusted basis, which I think as Dr. Vleugels said, very competitive and numerically higher by approximately 10 percentage points or more compared to the non-head-to-head comparators of dupi and lebri, and we're really excited about that.

I think conjunctivitis, we continue to see most importantly, that it's in line with the class, and it doesn't change treatment for the patients that get conjunctivitis. We saw at the mid-dose 10.6%, which is very in line with the class overall, but short-lived cases, again, median duration here, very similar to Part A, which was 30 days, both here and a little -- couple of days less than that in Part A. That compares to our comparison of dupi, which had a mean duration in the study of 172 days and more than 80% of cases resolved within 90 days compared to lebrikizumab, which showed about 41%. So we're obviously not causing longer cases and patients are doing well on this.

But really, again, to contextualize this and what conjunctivitis means in the clinic, I'll turn to Dr. Vleugels to talk through that.

Thank you, Carl. I really appreciate it. So perhaps just one comment on your first question. I think what's meaningful to me as an expert is that these higher order endpoints actually are much less susceptible to placebo responses. So in fact, the data that's presented here is actually sort of more impressive even than perhaps we would have expected and the fact that we see these high responses compared to other agents numerically is meaningful to us, and we would expect these to be replicated in the Phase III. And again, just sort of point to that increased efficacy that I mentioned that we think is truly mechanistically driven by what Carl just mentioned, including the higher exposures. So I think those higher order endpoint data is really what's going to help drive clinical decision-making in addition to the reduction of injection burden. So those 2 things coupled together is really what my colleagues will be extremely excited about.

In terms of the conjunctivitis, I know it was mentioned that I'm an inflammatory skin disease expert. So I see lots of inflammatory skin diseases other than atopic dermatitis. And it's just I feel really fortunate when I get to speak about a therapy that the main side effect is conjunctivitis because this is essentially something that my colleagues do not worry about. And I can kind of explain that by the fact that you can see that dupilumab and lebrikizumab are prescribed all the time by my colleagues, right? This is -- these are the biologics that we use and we have extreme comfort with because of their safety profile. And when we think about conjunctivitis, first, it's important to level set that atopic dermatitis patients have a higher rate of conjunctivitis at baseline, right? So that is just a common thing we see in these patients.

And the time that we're talking about with these IL-4, IL-13 medications is non-infectious conjunctivitis. So when you're counting patients, you can say, you may get a little red eye. And if that's the case, it's not from an infection. If you get that, let me know. And when patients get that, essentially, we almost always just give them eye drops. So literally over-the-counter eye drops, and that is it. And oftentimes, we don't have to do anything because it's very short-lived.

And so I've prescribed these medicines several thousand times since 2017 at this point, and I can kind of count on one hand where I've actually had to discontinue one of these therapies due to the conjunctivitis. And so again, this is not a side effect profile that is concerning to the prescribers of biologic therapies for atopic dermatitis. And I think that's just important to level set on. And then when we think about the data presented today, I think the zumilokibart data for the dose that's going to move forward into the Phase III is completely on par with other agents in this class. This is a class effect. And I think there is nothing to suggest that we would have a higher concern with zumilokibart relative to the other IL-4 and IL-13 therapies that my colleagues are extremely comfortable with.

The next question comes from the line of Akash Tewari from Jefferies.

This is Phoebe on for Akash. On the respiratory pipeline, we were just wondering kind of what external validation would you like to see before potentially moving zumi or the combo into COPD?

Yes. Thank you, Phoebe. I appreciate the question. There, I think we're excited about moving zumi in asthma. And then both zumi and our combo, we'll plan to kind of think about COPD likely after asthma for the mono. But then for the combo, that's something that we'll think about, and we'll share kind of plans later this year, potentially around combo plans in respiratory for our IL-13 TSLP, which could be inclusive of COPD.

The next question comes from the line of Alex Thompson from Stifel.

Congrats on the data. I guess a quick clarification and then a question. Could you comment on overall discontinuations beyond those due to adverse events at week 16 across arms? And then maybe in Part A, you showed some NRS changes quite early in the study. I wonder if you could comment on what you're seeing in Part B and if that's sort of a trend that you're seeing pull through at this point.

Yes. Thanks, Alex. I'll hand it to Carl for the 2 questions.

Yes. Thanks for the questions, Alex. I think on the first one, our overall discontinuation rate, we actually had a very low discontinuation rate here. It was about 6% across the whole study. So really low, especially compared to other Phase IIb trials and really lower than most Phase III trials. So really speaks to patients' ability to stay on the drug and treatment as well as the -- what we expect to be really consistent results regardless of analysis method or study moving forward.

And great question regarding the early itch changes. Here, this is kind of our top line data. So showing as much as we can here. We're seeing early itch and lesion changes on a weekly basis. This is what we reviewed here. And so we're seeing a lot of those in this data set already with lesion changes as early as a week and itch changes as early as the first 2 weeks. As we move forward and dig in more to this data over the coming weeks and months, we'll present more of that at upcoming medical conferences as well. So really excited for the profile we're seeing here and excited to continue to release more on the zumi profile throughout the year.

Our next question comes from the line of Michael Yee from UBS.

This is [ Kyle Yang ] for Michael Yee. Congrats on the data. So on the higher order endpoints, could you please help us understand, is there any particular reason that you saw better results for EASI-90 IGA 0/1 in your Part B given that you're using the same mid dose as the Part A study?

And the second question for Dr. Vleugels. Could you please help us understand how would you use this drug, assuming that the Phase III study replicates the results? And would you prefer to use this in biologics naive patients or experienced patients?

Yes. Thanks, Kyle. I'll hand it to Carl and then, of course, Dr. Vleugels.

Yes. So great question, right? I think that really on the higher order endpoints, I think the key here was size of trial and geographic distribution in terms of the updates to the Part B, I think that were really important for the study and really important for what we expect to do in the Phase III. We designed the Part B to be kind of as close as possible to our Phase III design. And so I think that replicability from Phase IIb our Part B to Phase III is really important, too. The bigger trial size, both on a treatment arm basis, but also on a -- especially on a placebo arm basis, I think, is also an important aspect of that, gave us a lot more power to detect the changes that we expected in EASI-90 IGA 0/1 and then here, as talked about earlier, EASI-100 and even VLDA are very low disease activity. So I think really size of trial and the global footprint, which is expected to be part of the Phase III trial.

Then I'll turn it to Dr. Vleugels for the second part of that question regarding how she would use the drug in clinic.

Thanks. This is a great question. So I -- if this drug were available today for both me and my dermatology colleagues who actually prescribe these medications, I would use this in over 95% of new starts. And the reason for that is that differentiated in terms of efficacy and injection burden. And this is really like the first time we can say that in this field. And I think this is really very important because other than a handful of patients where they have a concomitant disease that may need a different mechanistic pathway or, for example, someone who has full body erythroderma or full body disease that might need to be hospitalized. This is really the agent that is differentiated enough that it would take over the vast majority of new start patients.

I think we know for existing patients, we do have some percentage of patients that just like to stay on what they're on, and we know this from our psoriasis patients that we followed for a couple of decades, but it's typically about 4/5 or 80% of patients that are willing to change as long as there's a reduced injection burden even. And so what's interesting here is not only do we have a reduced injection burden, but we have what we seem to think would be higher efficacy as well. And so that would take me probably to my last comment on this, which is what's really interesting is what we know in dermatology is that we see dermatologists prefer to cycle between biologics before they move on to JAK inhibitors.

And the reason for that is because they are aligned with wanting to use biologics for safety even though these medicines don't have a substantially different efficacy profile. And so what's really unique here is that not only would we see a very high percentage of this for new starts as well as existing patients with efficacy, but patients who've been on a biologics and have so efficacy, this would be, of course, the treatment of choice to change because we also would expect a bump in efficacy.

So I think that's another really impactful category because we just haven't had anything that would move the needle in that category previously.

The next question comes from the line of Julian Harrison from BTIG.

Congrats on the progress. First, I'm wondering if you have any thoughts on what is driving zumi's itch benefit relative to other IL-13 and 4 receptor alpha inhibitors as well as [indiscernible]? Is there maybe a prevailing explanation there? And then second, given the strong data you've generated so far with zumi on a monotherapy basis, both in atopic derm and asthma, can you remind us how you're thinking about the combination opportunities going forward in both of those indications? Are they segmented to some extent?

Thanks, Julian. I'll hand it to Carl for the first question, and then I'm happy to take the second.

Yes. So great question. Obviously, we're really excited today with what we're seeing in terms of itch benefit, right, with the itch NRS of 4, which would be the itch data that would eventually end up on the label. So that's a really important aspect of that data, right, with over 50% of patients having that benefit by week 16. So very clear itch benefit with zumilokibart.

I really think 2 aspects of zumi are really driving this. One is we know that IL-13 has a direct impact on sensory neurons, too. So that early exposure and those higher exposures, we think are really important for having that sensory neuron benefit during the course of zumilokibart treatment. So I think that's one piece of it. And then the second piece of it is kind of the profound lesion control that we're seeing too as you decrease lesions, you get an itch benefit from that because the lesions are decreasing as well, too. So the more lesion control we get, right, here with almost 2/3 of patients getting to an EASI-75 and approaching half of patients getting to an EASI-90 and IGA 0/1 right, we're having a real huge decrease on lesions, which is also helping the itch too. So direct impact on sensory neurons and lesion control are both important to that itch benefit.

And then for the second question, I think that we've always said that the better the zumi monotherapy does, obviously, the higher the bar for combinations. I think in atopic derm, when we think about our 279 program, we want to see 10 points of better efficacy, not just versus dupi, but also on a cross-trial comparison basis versus zumi. So I think the bar will be high there appropriately so, and we'll allocate capital if it does meet that bar because it could still be the second-line drug of choice in atopic derm prior to JAKs, given JAKs have myriad black box warnings as has kind of been talked about.

And then for IL-13 TSLP and asthma, there, I think IL-13, it is a type 2, so right, high eosinophil targeted drug, and that's how we've designed the trial to go after that same population as dupi. But the addition of TSLP could expand the population to all eosinophils. So we think that there, there's potential efficacy benefit, but also just a broader population play that we'll consider as well.

The next question comes from the line of Geoff Meacham from Citigroup.

This is [ Jarwei ] on for Jeff. I guess, first of all, congrats on the EASI-75. I think we can all appreciate that mid-dose and high dose were pretty much on top of each other. But I guess when looking at the higher order endpoints, were there any PK/PD data that might explain why we didn't see similar levels of efficacy at week 16 for those endpoints? I'm just trying to better understand maybe why we didn't see some incremental benefits there?

And then maybe for Dr. Vleugels, building on an earlier question about use, given zumi does have a higher efficacy, could you envision a scenario where you would pull patients off the JAK inhibitor and turn them back to zumi? And then as a follow-up, we did notice that there were some UTIs in the dose arm. Do you find that clinically meaningful? And how does that relate to conjunctivitis as the treatment burden?

Thanks. Yes. So I appreciate the question. I think with the high dose, what we're seeing kind of at that single data point, we did see on the EASI-90 IGA, it's just noise. I think when we put out maintenance data next year, right, it will look very similar to the mid-dose. We did recapitulate the exposure response that we know exists with IL-13, and we're just capturing all that with the mid-dose, which is a huge win because we're getting there with 4 dosing days. So I think further data in the future that we release will show that they are just quite similar. And then happy to hand it to Dr. Vleugels for her thoughts as well.

Thank you. So I'm going to try to answer both questions. The first is whether dermatologists would pull patients off a JAK inhibitor. I think that this is highly likely, and this is coming from someone who I am considered a world expert in JAK inhibitor use in inflammatory diseases. And the challenge with JAK inhibitors is not that they don't have efficacy, it's that, by and large, the dermatology profession, both physicians and APPs have some hesitancy, some substantial hesitancy with their use given their box warning. And so the vast majority of prescriptions for JAK inhibitors are for the lower dose when there's 2 doses available.

We often have, as I mentioned, our clinicians cycling through many biologics even when they don't have substantial improvements in efficacy rather than putting patients on JAK inhibitors. But once the patient actually gets on a JAK inhibitor, what we often see is use of the lower dose, trying to taper them off as quickly as possible, trying to stop them as quickly as possible. And as I mentioned in my brief remarks, atopic dermatitis is a chronic illness, right? You could see from the patient demographics, the vast majority of patients have had their disease for over 20 years, right? So what we need is a highly efficacious therapy with a clean safety profile. And so the average dermatology provider will 100% take a patient off a medicine that has a box warning if they have a therapy that has similar clinical efficacy. So I think that is a fairly simple and straightforward question.

The second is about urinary tract infection. So I think that this is just essentially somewhat random. There's no mechanistic reason to have an increased risk of urinary tract infection on this type of medicine based on this mechanism. One thing I will align on just to kind of put this into clinical context, urinary tract infections are common enough that in major medical centers, we actually have visit pathways where our patients can send in a message and get their UTI treated without a traditional visit because they are so common. And so one of the challenges of doing clinical trials is when there are common things that happen to large pools of patients and there are ends in our study, which are on the smaller side when we're comparing dose ranging, we can have an increased number of something is common like a UTI scene, I have no concerns about this being a mechanistic concern of this class and don't expect to see any concerns in the Phase III.

So much. Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

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.

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 Apogee's latest developments and our goal of delivering a pipeline and a product with our lead program, zumilokibart, or APG777. Chief Medical Officer, Carl Dambkowski, will then walk us through the Phase Ib interim results of zumilokibart in patients with mild to moderate asthma.

Then Dr. Mario Castro, Professor and Chief of Pulmonary Critical Care and Sleep Medicine from the University of Kansas will walk us through the science behind IL-13 inhibition for asthma. Before moving on to the Q&A, Michael will summarize our vision for building a leading I&I company and our transformative year ahead. The subsequent Q&A will be led by Michael; Carl; Apogee's CFO, Jane Henderson; and Chief Commercial Officer, Jeff Hartness. We will also be joined by our KOL guest speaker, Dr. Mario Castro. I will now turn the call over to Michael.

Thanks, Noel, and thank you all for your time today. Welcome back from the holidays. We're very excited to share these data as we look ahead to what we believe will be a transformational year for Apogee. Today's data reinforce the broad potential of our lead program, APG777. With the approval of its international nonproprietary name, zumilokibart or zumi for short, we are moving rapidly to reaching more patients with the program now further derisked as a potential option for asthma.

Today, we will walk through our positive interim Phase Ib asthma results for zumi, which demonstrated a robust and durable effect on FeNO comparable to Dupixent. Interim data shows sustained suppression through 16 weeks for all patients following a single dose. Remarkably, this suppression remained through at least 32 weeks or 8 months for the subset of patients for which longer follow-up is available, reinforcing our belief that zumi could transform dosing not just in atopic derm, but across a broad range of expansion indications, including asthma.

Today's data represents the first of 4 critical readouts for Apogee this year. In Q1, we also plan to read out our 52-week maintenance data from Part A of zumi's APEX Phase II study in patients with moderate to severe atopic derm. We look forward to sharing that data and believe it has the potential to showcase Zumie's durability in atopic derm as well.

In the second quarter, we look forward to data reinforcing Zumie's 16-week induction profile when we read out our dose optimization study, APEX Part B in atopic derm. We exceeded our enrollment target ahead of schedule for this study, finishing with 347 patients, thanks to strong enthusiasm from both patients and physicians. This accelerated readout positions us to initiate our Phase III studies this year, potentially accelerating our path for the BLA.

We believe we are well underway in establishing a potential best-in-class profile for zumi within the future $50 billion atopic derm market and are on a path to a planned potential 2029 launch with every 3- or 6-month dosing. In addition to the monotherapy potential of zumi, we are evaluating fixed-dose combination approaches. The first of those, which combines IL-13 and OX40 ligand inhibition is APG279.

279 is currently enrolling a study in atopic derm head-to-head versus the market leader, Dupixent. Given strong interest from patients and physicians, we have expanded that study following an interim safety analysis and remain on track to read out the study in the second half of 2026. We are also exploring the combination of IL-13 with TSLP inhibition via our fixed-dose combination APG273, and we'll share more details on our approach in respiratory conditions later this year.

As shown with today's data in asthma, we see a future for zumi mono and combo approaches across numerous blockbuster indications. Taking a closer look at the potential for zumi, our pipeline and product approach is backed by the scientific mechanism of IL-13 as a core driver of multiple I&I diseases. We have already showcased this in the derm setting with positive APEX Part A data last year.

Reinforcing the data we're presenting today in asthma, we observed improvements across a number of comorbid conditions as part of our initial APEX Part A atopic derm data. Specifically, for patients with comorbid asthma or sinusitis in that APEX study, we observed improvements in their comorbid conditions of asthma and sinusitis as measured by improvements in ACQ-5 and SNOT-22, respectively.

We believe this pipeline and product approach has now been validated in respiratory conditions with today's positive Phase Ib asthma results, and we look forward to expeditiously moving into further development. We are very excited by the potential of zumi and the data we have seen to date further encourage our hypothesis that zumi can enable 3- or 6-month dosing for even more patients living with I&I conditions.

With asthma data now in hand, we are entering late-stage clinical development in 2 of the largest I&I markets, asthma and atopic derm. Atopic derm is the largest and fastest-growing I&I market with roughly 15% projected growth through 2030, while asthma represents the second largest I&I market and an important comorbidity with 30% of atopic derm patients having comorbid asthma.

With clinical proof of concept for zumi in both indications, we believe we have the opportunity to deliver potentially best-in-class therapies across these large underpenetrated diseases that still have significant unmet need. I will now turn the call over to Carl to walk us through the Phase Ib asthma data.

Thanks, Michael, and thank you all for joining today. I'm excited to share the zumilokibart data in asthma today. Zumilokibart achieved or exceeded all trial objectives. First, a single dose of 720 milligrams of zumilokibart was well tolerated, confirming the safety profile for this treatment as a monotherapy in patients with asthma.

Second, the magnitude of FeNO reduction demonstrated by zumilokibart was in line with standard of care treatments such as dupilumab. Specifically, zumilokibart demonstrated a 45 parts per billion decrease from baseline or 60% decrease from baseline in FeNO after a single 720-milligram dose. And finally, zumilokibart's impact on FeNO was also durable, showing sustained FeNO suppression after a single dose for at least 16 weeks, which was the limit of follow-up available for all patients.

Furthermore, in the subset of patients with data beyond 16 weeks, suppression was sustained through 32 weeks, which was the longest available follow-up data at the time of interim analysis. The sustained suppression of FeNO after a single 720-milligram dose of zumilokibart supports dosing every 3 or 6 months in future studies. IL-13 biology has long been implicated as a key cytokine in asthma.

However, previous trials evaluating lebrikizumab and IL-13 antibody in asthma patients did not always bear out positive results. We believe the subpart efficacy observed in these prior trials was driven by underdosing and broad patient selection. In these studies specifically, the highest lebrikizumab asthma dose used was more than fourfold lower than what is approved in atopic dermatitis and enrollment was not enriched for patients with T2 inflammation.

In contrast, the zumilokibart Phase Ib asthma dose is modeled to have exposures at least 3x higher than those achieved in lebrikizumab asthma trials and much more similar to successful atopic dermatitis trials for lebrikizumab. Additionally, we designed the Phase Ib to enrich for patients with type 2 inflammation by requiring baseline FeNO of 25 parts per billion or greater.

The Phase Ib was a double-blind, placebo-controlled trial that evaluated the safety and tolerability of zumilokibart in 19 adult patients with mild to moderate asthma and a FeNO baseline equal to or greater than 25 parts per million, which represents a population enriched for type 2 inflammation. This trial also evaluated the magnitude and durability of FeNO suppression by zumilokibart as well as other pharmacokinetic and pharmacodynamic endpoints.

Participants were randomized 3:1, receiving a single dose of 720 milligrams of zumilokibart or placebo on day 1. FeNO is a well-established biomarker of type 2 airway inflammation. FeNO has consistently shown the strongest correlation with asthma exacerbations across available biomarkers. Importantly, the FDA has suggested that FeNO may also serve as a potential surrogate marker of treatment response for asthma biologics, particularly those targeting the IL-4 and IL-13 pathways.

Baseline characteristics and demographics outlined on this slide were generally well balanced and in line with expectations for this patient population. In this study, zumilokibart has been well tolerated with a favorable safety profile across all patients. The safety profile is in line with expectations of therapies targeting IL-13 and what we've seen to date with zumilokibart in other studies.

The only treatment-emergent adverse event observed in more than 1 patient was gastroesophageal reflux disease. There were 2 cases and both were grade 1. There were no grade 3 or higher treatment-emergent adverse events or any serious adverse events. There were no observed cases of conjunctivitis or injection site reactions. The key analysis for this study was FeNO suppression, both in terms of magnitude and durability after a single dose of zumilokibart.

Zumilokibart both rapidly and durably suppressed FeNO through 16 weeks and demonstrated a maximum mean reduction of 45 parts per billion with suppression sustained through week 16, which was the limit of follow-up available for all patients. Similar results were demonstrated when looking at percent change from baseline in FeNO with a maximum mean percent reduction of 60% and durable changes through week 16.

In looking beyond week 16, available follow-up data demonstrates continued suppression of FeNO on both an absolute and percent basis to week 32, the limit of our available follow-up. Durable FeNO reduction after a single 720-milligram dose of zumilokibart supports a dosing strategy of every 3 or 6 months in future asthma trials.

When viewed alongside a broad set of mechanisms and agents, the week 12 FeNO reduction observed with a single dose of zumilokibart is in line with effective and approved agents such as Dupixent and Tezspire, which are dosed 3 to 6x as frequently during the same period. The magnitude of FeNO suppression for zumilokibart was similar to that of Apogee's own IL-4 receptor alpha targeting agent, APG808. As mentioned, zumilokibart demonstrated durability out to 32 weeks post dose for patients with available data.

In contrast, APG808, which also incorporates half-life extension technology, began to show rebound in FeNO 8 weeks after the last dose. We set out to design and execute a trial for zumilokibart that would demonstrate the ability of an IL-13 targeted agent to show FeNO changes in line with standard of care as well as durability of those changes supporting at least every 3-month dosing.

To do this, the zumilokibart Phase Ib trial in mild to moderate asthma patients enriched for patients with type 2 inflammation and tested a higher drug exposure than previously used for IL-13 agents in asthma studies. The study achieved or exceeded all trial objectives, including demonstrating a well-tolerated safety profile, robust magnitude of FeNO suppression in line with standard of care agents such as dupilumab and a durable FeNO suppression 16 weeks post dose, which is the limit of follow-up data for all patients and further in the subset of patients who had 32-week data showed a robust and sustained FeNO suppression out to 32 weeks for those with data available past week 16.

We also are observing positive trends for FEV1 and type 2 inflammatory biomarkers for available data. We look forward to sharing further data from this trial at an upcoming medical conference. This data, we believe, is supportive of every 3- or 6-month dosing and of advancing zumilokibart in additional asthma studies. We plan to disclose additional plans for our asthma program later this year.

And now I have the great honor of introducing Dr. Mario Castro, L.E. Phillips and Lenora Carr Phillips Professor and Chief of the Pulmonary Critical Care and Sleep Medicine Division at the University of Kansas Medical Center. Dr. Castro is a widely recognized expert in asthma with over 300 peer-reviewed publications, including lead authorship on the Dupixent pivotal Phase III QUEST study. I'll now turn it to Dr. Castro to help contextualize the zumilokibart results. Thank you.

Hi. I'm Mario Castro at the University of Kansas School of Medicine. Thank you, Carl. I'm thrilled to be part of this important day for Apogee. As demonstrated here, IL-13, we know is a key mediator in asthma. We know that it's one of the type 2 cytokines, IL-4, 5 and 13, and this is one that has been targeted by a number of different biologics for asthma.

We know that IL-13 drives a lot of those key features we see in severe asthmatics such as mucus hypersecretion, airway hyperactivity and eosinophilic inflammation. As demonstrated in this study, we demonstrated that the biopsies from patients with severe asthma, both atopic and non-atopic had marked increase in message for IL-13. This next study we conducted as part of our severe asthma research program to study the key features of airway remodeling.

We know that in airway remodeling, this includes epithelial thickening, subepithelial fibrosis, goblet cell hyperplasia and increased smooth muscle mass. What we demonstrated here is marked upregulation of MUC5AC in the airway epithelium in patients with severe asthma. And this was also accompanied by a decrease in cilia-related genes in mucus clearance.

This demonstrates the key role of IL-13 in terms of driving this disease process in terms of greater mucus production and decrease in mucociliary clearance. This also is collaborated by the study on the right-hand side, which demonstrates that the green staining is MUC5AC, the red staining being cilia. When you add IL-13 to epithelial cells, you see this marked diminution in the cilia and marked upregulation of MUC5AC.

These key features of airway remodeling lead to airflow obstruction and hyperresponsiveness. Next, let's move on to the clinical studies that have been done with IL-13. You may recall lebrikizumab has been studied in previous clinical trials, but did not demonstrate a significant benefit. What we learned though in subsequent analysis in this study published by [ Jonathan Korn ] is that it also depends on the subset of patients you select.

As demonstrated here, if you target those with a high T2 expression, either by exhaled nitric oxide, 50 parts per billion or greater or looking at blood eosinophils of 300 or greater. Now actually, lebrikizumab does work in reducing exacerbations in these patients with high T2 biomarkers. This again suggests that IL-13 inhibition would be effective in the right patient that has high T2 inflammation.

So to summarize, what we've briefly demonstrated here is the key role that IL-13 plays in asthma. We know that this is really a key player, not only in the disease process, but in the remodeling process that leads to progressive disability in our patients as demonstrated by their chronic airflow obstruction, repeated exacerbations and lack of control. This post-hoc analysis that we shared with you with lebrikizumab, another anti-IL-13 blocker, did demonstrate that if you select the right patient with the right monoclonal antibody, anti-IL-13 in this case, that there was a significant reduction in asthma exacerbations.

I'm thrilled to be part of the Apogee data in discussing this with you, the Phase I zumilokibart interim data. This Phase I study demonstrates a significant and durable improvement in lung function in this Phase I study and suppression of exhaled nitric oxide with a single dose and also with an acceptable safety profile as one we expect from IL-13 inhibition in appropriately selected population.

These results are very encouraging, and I look forward to continued work with the Apogee team as they develop zumi for patients. I will now pass the call back over to Michael for closing remarks.

Thank you, Dr. Castro. The growing asthma biologics market will soon exceed $15 billion and is evolving towards agents that offer longer dosing intervals. Dupixent has become the market leader given its unique position as the only biologic approved for both asthma and atopic derm, but it is dosed every 2 weeks. We.

Believe zumi has the potential to become the leading type 2 inflammatory therapy, pairing robust disease control in asthma and atopic derm with an improved dosing profile that could transform patient care. We believe zumi is well positioned to expand into additional indications and realize its potential for a pipeline and a product.

Existing therapies face inherent limitations in balancing efficacy with dosing frequency. Zumi has the potential to change that and could be the first long-acting biologic approved for both asthma and atopic derm, offering dosing every 3 or 6 months and the opportunity to transform the treatment paradigm by reducing the burden of frequent injections for patients.

With APEX atopic derm readouts anticipated in the first and second quarters of this year and the planned initiation of the ASPIRE trial in asthma, zumi is positioned for expansion across several of the largest I&I markets. We see further potential in eosinophilic esophagitis, COPD and a number of type 2 inflammatory conditions. Looking ahead, we are thrilled to have kicked off 2026 with our first data set for zumi.

This marks the beginning of what we believe will be a transformational year as we plan to deliver multiple significant clinical data readouts across our mono and combination programs and advance in the late-stage Phase III development. We will continue to report results from our zumi program throughout the year with APEX data in atopic derm expected in Q1 for 52-week Part A maintenance and Q2 for 16-week Part B induction.

The second half of the year will be pivotal for us as we share the first data for APG279 in the head-to-head trial against Dupixent and initiate our first Phase III trial for zumi in atopic derm. Thank you all for joining us today. With multiple catalysts ahead and strong clinical momentum, we are excited about the year to come and the opportunity to deliver potentially best-in-class medicines that can make a meaningful difference for patients across a broad range of I&I diseases. I'll now hand the call back to the operator to begin the Q&A. To help us manage the discussion, we ask that each caller please limit themselves to one question. Thank you.

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

So actually, I'm going to go a little bit more on a commercial direction here. Can you guys just comment and give us your thoughts on the impact that both a long-acting treatment in asthma that could also be used in combination in concert with an atopic dermatitis label, what would that mean from a commercial perspective from your -- in your view, largely because it's been our view here that IL-13 would work in asthma, that this would be highly differentiating and that it also basically opens up a much broader opportunity to target allergists and pulmonologists, but I think there may be some other commercial benefits beyond that as well.

Thanks, Seamus. I appreciate the question. I'll comment briefly and then hand it to Jeff. We felt from the beginning that given kind of the atopic triad, many of these patients that have atopic dermatitis, up to 30% of them and even more in the pediatric setting have comorbid asthma.

So the ability to have the conviction that our agent will work for both atopic derm and asthma and be potentially the only long-acting biologic that will have proof of concept and both on the label is quite differentiated from other drugs in development. Jeff and his team have spent a lot of time kind of mapping this out and the impact it could have. So Jeff, I'll hand it to you to comment on the different advantages this could bring us.

Yes. Thanks for the question, Seamus. I think it's important to note that right now, in the biologic asthma space, Dupixent is the market leader. And that is in spite of being fourth to market and in spite of having every 2-week dosing. And we believe the reason that they're the market leader is, in fact, that they have both the indications in AD as well as asthma.

And with Michael's point of 30% of these patients having comorbidities, that is a really important space that those patients are currently just getting Dupixent. So we will be able to walk into that space, quickly have an impact with being the only product with both indications and having the extended dose options that we plan on having. I think secondarily, aside from just driving that volume and that revenue, I think it's important when you think about it from an access perspective, we have been clear about our confidence level in having early access for zumilokibart with payers for atopic dermatitis.

What this allows us is to strengthen that position, not just by having a line extension within the contract to also cover asthma, but it strengthens our position because, as a reminder, these 2 indications are, in fact, the largest indications that Dupixent has both by volume and revenue. So it strengthens our position to really get not just the access but get it at the right price.

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

This is [ Phoebe ] on for Akash. Just looking towards Sanofi's TSLP and IL-13 bispecific asthma readout in this half of the year, do you think, a, this can hit in the all-comer population here and in COPD? And b, what level of benefit do you have to show in the EOS less than 150 subgroup to consider this sort of clinically meaningful?

Yes. Thank you, [ Phoebe ]. I'll hand it off to Carl to speak to that.

Yes. Thanks for the question. I think, obviously, we're tracking closely with Sanofi's TSLP, IL-13 antibody in addition to the zumi monotherapy data we're showing here, which, as Jeff and Michael hit on, we think will be a huge benefit for patients as a monotherapy itself. We're also looking into the combination of zumi and APG333, which we call APG279.

So the fixed-dose combo of IL -- sorry, 273, the fixed-dose combo of IL-13 and TSLP as a potential benefit for patients. We do think the main benefit of the combination therapy, as you suggested, is in the non-T2-enriched population, meaning in the population that is, for example, less than 150 EOs, mechanistically, we're encouraged by what the combination could show there.

And so we think that Sanofi and down the line ourselves could hit both in an all-comers population as well as in COPD population, which we know is much more heterogeneous in terms of cytokines and disease course as well.

We think the bar in the EOs less than 150 is somewhere between a 40% and 50% reduction in AERs, which would really show benefit there more similar to what Dupi and tezi have shown in the T2 enriched population. And so that's what we'll be really looking for there, both in the Sanofi data and in the future for our own combination.

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

Congratulations on the tremendous results in asthma here. Regarding the ASPIRE trial that you're planning for, I don't believe you guys said whether it would be Phase II or Phase III. So considering the fact that the AD Phase II program is exploring dose ranging and that you guys like to run fast in development, is it possible that the ASPIRE trial could be a pivotal trial in asthma?

Thanks, Tyler. I appreciate the question. This data is hot off the press. We're evaluating the most expeditious path and how to move forward. Obviously, we're quite excited about this data and thinking about how do we get this approved into patients as quickly as possible, but more to come on the trial design later this year.

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

Congrats on the data as well. I guess maybe to the specific data set itself, I wonder if you could comment on how representative you think this patient population is relative to how you might think about enrolling your next study? And then also if you could comment on the placebo response you saw on FeNO and any underlying changes in background therapy, et cetera, or what could have driven that?

Yes. Thanks, Alex. Our eosinophils here came in right around 300 on average. So we saw a nice range kind of 150, 100 plus, which pretty closely matches the Dupixent label of eosinophilia and that greater than 150 benefit or about 2/3 of asthma overall. We feel like it was a fairly representative population of that type 2 as defined by EOs greater than 150 population. And Carl to speak to anything else.

Yes. No, I agree. I think that our goal here was to do a T2-enriched population, but one that would be representative of what we would do in future trials. And we saw almost all patients in this cohort were EOs 150 or greater, which we think is fairly representative there. As Michael said, the average EOs count was around 300, which is a little lower than what we've seen in Dupi trial, which have been anywhere from the mid-350s to high 400s depending on the trial.

So overall, we feel it's a T2-enriched population that would be representative in that nature of what we would do in future studies. On the second part of the question in terms of placebo response, I think we're seeing 2 things here is one, we had a fairly high baseline FeNO as you can see. So there's just some variability that we see overall in terms of the placebo arm as well. And then I think the small end is contributing there as well.

I think whether you look at it on an absolute or placebo-adjusted basis, I think the FeNO results to us demonstrate what we wanted to in this study, which is that an IL-13 therapy with the right dose and the right patient selection can be as effective as dupilumab and other effective agents here. And then obviously, we're really excited about the durability too. But whatever way you look at it, I think it's showing that when you design the right study, IL-13 should be as effective as IL-4 receptor alpha targeting.

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

Congratulations on these data. Keeping in mind patients in the study only received a single dose of zumi. Do you have any thoughts or expectations with regards to deepening responses following multiple doses in future studies?

And then I think I know the answer to this next question, but just to clarify, do you necessarily have to have the best-in-category biologic in asthma for commercial success here? Or is it your view that first-in-class dual labeling is a sufficiently positive outcome long term?

Yes. Thanks, Julian. I appreciate the questions. I'll start and then I'll hand it to Jeff to speak to the -- what we think will be for commercial success piece. In terms of deepening following multiple doses, I think we look forward to running additional studies where we'll test obviously multiple doses and multiple dose regimens to just see how disease control could be over time.

We do know that in asthma, COPD and respiratory conditions in particular, the more that you can have a drug on board to the fewer kind of trough levels you can have to prevent exacerbations or any risk of target coverage not being maintained for whatever any assault on the respiratory system could happen is key.

And of course, in the real world, that has led to, right, much improved adherence and outcomes for longer-acting agents and hence, our commercial success, which I think feeds into the second part of the question that I'll hand over to Jeff.

Yes. Thank you, Michael, and thanks for the question, Julian. I would say to expand on that, I think, first and foremost, having the dual labeling and the expanded dosing is, in fact, key to the commercial success. I think the -- when you look at Dupixent for asthma and you look at their adherence rates in the first year, they're extremely low in the 55% range. And with asthma, as you know, this really does -- the adherence rate really does impact outcomes.

In fact, it impacts overall health care costs with hospitalizations and emergency department visits as well. So we believe that if we have a similar efficacy and safety profile with the expanded dosing and the dual labeling, this positions us extremely well to become the market leader in both indications.

Your next question comes from the line of Geoff Meacham from Citi.

This is Nishant on for Jeff. So you also saw positive trends in FEV1. Of course, it's a small end. Can you provide more qualitative or quantitative color on the magnitude of this FEV1 change compared to the changes seen with Dupixent in some of the similar studies?

Yes. No, thank you for the question. I'll hand it off to Carl to just speak to kind of qualitatively what we saw. We are going to keep the quantitative piece for later on at medical conferences as we have a lot of data that we're still working through here and are excited to share in the future. And then I would love to ask Dr. Castro to also comment on why it's exciting in this population to see FEV1 even with a small patient population.

Yes. As Michael said, I think what we're really encouraged by and what we weren't expecting in the study is positive trends in FEV1. Obviously, the main goal of this study and why we're releasing the data today was to show the FeNO changes over time, both in magnitude as well as durability, but we have more data we're working through that we'll release at medical conferences later this year as well as help inform our design of the ASPIRE trial, which we'll release more on later this year.

So I'll turn it over to Dr. Castro and maybe I'll ask him to comment on 2 things. One is why FEV1 matters, but also why FeNO has kind of been maybe more important and kind of the best link to future studies as well too. Dr. Castro, if you could take it.

Sure. It's Mario Castro. So in all of our asthma trials, FEV1 has always been kind of the gold standard. And to see FEV1 improvements in this patient population in the Phase I study is actually quite positive in that we're seeing it already as a signal. Sometimes we don't see this until later Phase II studies.

So I think this is in line with what we expect to see in subsequent pivotal studies that are going to be done. The second part of that question in terms of the FeNO as a biomarker and being important predictive of future response. When we think about this pathway, the IL-13 pathway, it's been pretty consistent as a biomarker that is predictive of other outcomes that are going to be important down the road, not only lung function, but also reduction in exacerbation.

So we're quite impressed by this magnitude of reduction in FeNO and that, that should again correlate with what we'll see with other clinical outcomes.

Your next question comes from the line of David Nierengarten from Wedbush Securities.

I just had one for Dr. Castro. I know the off-label use, but if you have treated patients who maybe have been -- who fit the profile of the patient who would benefit from IL-13 if you treated any of your patients with EBGLYSS and if the results were consistent with the post-hoc analysis from the previous studies.

Could I clarify off-label use in terms of what type patients?

Treating asthma. Yes, treating the patients you might expect would benefit the high eosinophils or other markers?

Using that drug like this one or...

EBGLYSS. Yes, using EBGLYSS IL-13.

Okay. Yes. So really, I think I'm impressed by the post-hoc data that I shared with you from Jonathan Korn's paper in that when you select the right patient population, then we see that pretty marked reduction in exacerbations and improvement in lung function. So I haven't used this off-label. It's not really been available for us to use in that format clinically. But that data does suggest that this would have the effect that we expect.

Your next question comes from the line of Brian Abrahams from RBC Capital Markets.

Congrats on the data. I guess more broadly speaking, I was wondering if you could maybe comment a little bit more about the PK/PD that you're observing here versus what you've seen in your prior studies? And maybe how to apply the safety findings and the durability here to other indications like AD.

Yes. Thanks, Brian. I appreciate the questions. So here, I think the PK/PD is very much in line with what we've seen with our other indications. It continues to be a very well-behaved antibody, right, very low ADA incidents, none observed here and kind of that rapid and then deep sustained durable reduction. And in different biomarkers or functional endpoints.

On the safety side, I do want to caution that, right, Dupixent, IL-4 kind of IL-13 inhibitor pathways, they do see conjunctivitis as do we in the context of derm conditions, but a much lower rate in the context of asthma, EoE, COPD expansion indications that are non-derm. So I think what we're seeing here is a continued very well-behaved drug that doesn't see kind of that conjunctival phenomena that's known by physicians to occur solely in the context of derm.

And I think when we look at kind of our overall safety profile today broadly, we continue to have a very well-behaved, well-tolerated, very safe mechanism of antibody as would be expected with the class.

The next question comes from the line of David Hoang from Deutsche Bank.

So I think you -- I believe you mentioned with the APG808 molecule, your IL-4 RA, you had looked at that and you saw a bounce back in FeNO at 8 weeks. And here, obviously, the durability is going out to 16 weeks plus with IL-13. Can you just comment on if that is sort of in line with your expectations around kind of the biology here and the durability with the IL-13, additional durability, what is driving that versus the -- less with the 808 molecule?

Yes, I appreciate it. We're -- last year ran this very similar experiment with 808. And I think what gives us a lot of excitement and conviction in the durability that we see with zumi that we're sharing today is that we did not see that with our IL-4 receptor alpha half-life extended optimized antibody. So there is a high amount of target-mediated drug disposition with receptor bound targets.

So even with -- our view is that with our 808, we would need about 2 injections to even get to every 2- to 3-month dosing, whereas here following the single dose, right, we're out to 16 weeks for all patients or 8 months for those that we have follow-up with that kind of -- without the bounce back being seen. So 8 months versus 8 weeks for us is a pretty clear advantage when we think about the ability of an IL-13 mono or future combos versus IL-4 backbone, either monos or bispecifics because of the inherent biology and high target concentration of IL-4 receptor, it just is a shorter dosing interval.

Your next question comes from the line of Joe Catanzaro from Mizuho.

Appreciate the update. Maybe one for me, somewhat related to the PK/PD relationship. I'm wondering if the durability of FeNO reductions out to 32 weeks aligns with exposures at that time point that you would expect to be efficacious? And if so, how much beyond week 32 do you expect exposures to remain above that efficacious level?

Yes. Thanks. I'll hand it off to Carl.

Yes. So great question. Thanks for that. I think that part of the design for doing this dose in zumi here is that the 12-week exposures align with Q12-week steady-state exposures of zumi in our AD study and the 24-week exposures align approximately with the Q24 every 6-month dose in the zumi maintenance study, which we'll be releasing data on -- in Q1.

I know that doesn't exactly answer your question, but just saying how we got there, too. And an open question for us and based on all the data we have is, do you even need those exposure targets to maintain responses out to 3 and 6 months or maybe beyond. So I think we're very encouraged by the exposures we're seeing here and the durability of response out to 32 weeks or 8 months as Michael said, and it opens up questions of exactly how much drug you need to maintain these responses, not only in asthma as we're seeing with FeNO here, but for our maintenance data in AD in Q1 of this year.

We have run out of time for questions in the question-and-answer session. And with that, the question-and-answer session has concluded. Thank you for joining Apogee Therapeutics conference call. Have a great day.

Welcome to the second day of the Citi Global Healthcare Conference. So I'm Geoff Meacham. I'm the senior biopharma analyst. My team here too, Nishant, Ross, Mary Kate.

So we're thrilled to have Apogee with us. So we have Jane Henderson, CFO. We have Jeff Hartness, CCO. So guys, thanks for joining us. Good to see you.

Thank you, Geoff.

Good to see you as well.

So we have some questions, but do you want to like kind of give maybe a quick summary? Or do you want to get ready into questions? It's totally up to you.

I can give a very quick summary. First of all, thank you for having us. We're really pleased to be here and look forward to a robust discussion. 2026 is a transformative year of important clinical readouts for Apogee. And we're going to walk through each of those in our discussion today. Some of those we accelerated recently. So we have Q1, two data points for our LEAP program, 777 in AD, we have maintenance data. We also have asthma data for 777 in Q1. And then in Q2, we have our Part B Phase II, where we're testing the dose response curve for 777 in AD. And then finally, in the second half, we have our combo trial of IL-13 and OX40 ligand, where we have a Phase Ib ongoing in head-to-head against DUPI. So an important year for us and look forward to going through more details with you.

Yes, yes. Well, Jane, let's talk about the initial 777 data. I think the positioning was match DUPIXENT in efficacy, similar tolerability and then you have the better dosing profile. The only nuance of that, I think investors are past it now, but was the conjunctivitis. Maybe just give us some context for that, like why that's not a big deal and looking forward, obviously, you guys have your expanded trial and you're going to have data, more meaningful data next year?

Sure. Absolutely. So when we talk to physicians and KOLs, and they see our data from Part A, they say it's in line with real-world experience with the DUPIXENT and with Ebglyss. What's interesting in trials now is investigators ask patients, do you have red eye? When Dupi and Ebglyss trials were run, physicians would ask patients are you feeling okay? So certainly, it's now being looked for. They are typically mild and either resolved on their own or they are treated with over-the-counter Visine.

So as we talk to KOLs and our own market research and those that are done by GuidePoint and others, our physicians do not see our conjunctivitis data to date as a reason why 777 would not be the biologic of choice all around that transformative dosing of every 3 and 6 months.

And just a follow-up to that. When you talk to physicians in the community that love experience with Dupi, maybe what are some of the opportunities that you may have with 777? What are some of the pushbacks you get with like, why don't you use more Dupi? What's the sort of the theme and either discontinuations or underperforming patients that may be an opportunity for you guys?

Sure. Well, I'll touch upon it and then Jeff can talk about some of his market research and conversations with the KOLs. So the #1 reason why DUPIXENT is discontinued and within two years, over 50% of patients go off of DUPIXENT. There is needle fatigue, but there's also injection site pain. And that is where we see the discontinuation rate, not from conjunctivitis. And just as a reminder for our Part A trial, we did not see any ISRs in our Part A data to date, not that we'll never see that, but to date, we haven't seen it.

Yes. And maybe I'll add, Geoff. The biggest opportunity in the AD biologics space is really biologic penetration. We are at about 10% right now, much less so than other I&I diseases, plaque psoriasis or IBD, 10%. So it's a huge opportunity for us. Right now, when you look at patients that are on topicals, they're less likely to move over to a biologic, but they need to take 9 dosing days and induction and then they're injecting every 2 weeks.

So 26 a year versus the ability to move into maintenance with an every 2 to 4 times a year, 777. So we fully expect an opportunity with physicians and with patients is to drive much deeper into that biologic penetration with 777.

Okay. Yes. That's helpful. And maybe from a -- I know we're going to talk about the Part B of the study. What opportunities do you see for differentiation there? Maybe what does kind of a win look like from a clinical perspective and we can talk about the commercial implications?

I'll start, and then I'll have Jeff add. So first of all, on Part A, we see a win with the dosing that we could provide patients of every 3- and 6-month dosing, right? We are the first company to test maintenance dosing in Part B, and it will inform our Phase III dosing where in any scenario, we're going to be testing every 3- and 6-month dosing in maintenance. So there's a win there. For Part B, our goal is to replicate the strong data that we saw in Part A, where we saw very strong EASI-75 results, whether it was absolute or placebo adjusted, including similar efficacy on IgA-01, and EASI-90 to Dupi and lebri.

What we are doing in Part B is testing the dose response curve. So we are testing a lower dose so that we can go to the agency with a lowest efficacious dose but importantly, we also want to see whether we're leaving any efficacy on the table. So we are also testing a higher dose in our Part B and that higher dose is twice the exposure of Ebglyss.

Yes. And commercially speaking, Geoff, I think when you look at the product profile that we presented coming out of IIa, it is clearly the most preferred product profile of any biologic in AD by both physicians and patients. So if in Part B, we're able to replicate that product profile, we see that as a huge win. Anything above and beyond that, it doesn't change the way we go to market. It doesn't change our marketing strategy. We already have the most preferred product with the Part A data.

So it could impact things like gross to net positively for us, if there is any additional efficacy that's left on the table, but we certainly do not need that to win.

Yes.

Yes. Dosing alone wins.

What are the challenges, though? And do you -- and moving from maybe 3 months to 6 months, do you, from a mechanism or from a tolerability perspective, do you add extra risk if you have higher dose? Or I just wasn't sure what the -- maybe the nuances between every 3 months is very differentiating in its own right. But like 6 months is like a real like Gold Star, like that's an amazingly commercially relevant product. Obviously, you want to aspire for that, but I wasn't sure of the extra challenges to get to that and frequent of the dosing.

Well, we have confidence based on what we see from a PK modeling point of view for every 6 months. So just as a reminder, our every 3-month dosing is exposure that is slightly higher than what is seen with lebri and our every 6 month is slightly lower. So all we would need to do if we saw in our Part A maintenance, a lower efficacy on the 6 months is to increase the dose in our Phase III trial. If we saw the efficacy that we're looking for, then we can decrease the dose of every 3 months. So again, in any scenario, we are going to test both and launch with both. It's just going to be optimizing that dosing going into the Phase III.

Okay. But you don't engage, for example, the immune system or have other, it's all in your mind, like just PK, PD and pharmacodynamic kind of situation?

That's what we've seen generally with this class and also with our own data so far.

Yes. Okay.

Yes, along those lines, any PK/PD metrics that you will show in the maintenance -- the part A maintenance data that gives more confidence in 777's profile versus dupi?

The answer that we're looking for that matters and is well laid out from DUPIXENT, the market leader, is showing maintenance of response at 52 weeks. So for those patients that achieved EASI-75 or IgA-01 response, what is the percentage that is maintained at 52 weeks? And for DUPIXENT for EASI-75, that's just over 70%. For IgA-01, it's just over 50%, so that is what we'll be looking for to then determine how to optimize that Phase III dosing strategy.

And recently, you also presented data at EADV about the rapid itch relief profile of 777. So just give us some color on how important that property is for the drug and how that competes with the other kind of in the market -- revenue market.

Yes. So thanks for the question. We are thrilled with the data that we presented at EADV on statistical significance for itch at 48 hours. And I'll tell you, it is really important to the product profile. So when you ask physicians, what's most important for them, they'll tell you EASI-75 scores when they're trying to decide what product to use for their patients. When you ask patients what's most important, the rapid itch relief kind of floats to the top.

And I think you can see this in the launch of Nimluvio, right? Really strong launch, subpar in terms of lesion control, but really good on itch. So it shows the value of that itch. And for us to come forward with a product that has statistical significance on itch at 48 hours as good or better lesion control with EASI-75 than DUPIXENT or Ebglyss and the dosing of SKYRIZI, it's really the trifecta. It's the perfect product in the biologics space for AD patients.

And we're really diving into what's taking place with the sensory neurons. And if you look at the IL-31, it's clear in the Nimluvio data, that IL-31 does, in fact, impact those sensory neurons. For us, we've seen a lot of great work come out of Brian Kim's lab out in Mount Sinai, which now we know that IL-13 at the right dose, at these higher exposures does, in fact, have impact on those sensory neurons. And we believe that is why we're able to show that 48-hour relief.

I'm just going to say, is there -- I know from the Part A, there wasn't like -- it's hard to look into some of the smaller numbers. But is there any, like a DUPIXENT experience patients, someone who has either failed or nonresponder or is that a more difficult patient for you guys? And is that a meaningful part of the market? I'm just looking to a larger Phase III and like what you kind of focus on?

Yes. So to -- Jeff will address the market. To clarify in Part A, we had all biologic naive. In Part B, we are testing up to 20% biologic experience. So we will see the answer from that data that we expect in Q2 on Part B induction. From a market point of view, it's interesting in terms of new patients versus existing.

Yes. So that's part of the reason why we will, in fact, have up to 20% biologic experienced in our IIb. It is an important part of this market. And the reason is because when you look at DUPIXENT, only one out of two patients actually reach an EASI-75, right? And that's a critical end point for physicians because it really moves patients from moderate disease to mild disease whenever you move to EASI-75. So we believe that there are really two major areas that we will build share with APG777. The first is simple, and that is, in fact, switches. So you're going to have patients that want more efficacy or you're going to have patients that just either have ISRs or they're just -- they don't want to take injections every two weeks.

Those patients will look to move. In fact, we have some really strong market research with patients, even controlled patients who would prefer to switch at a very high rate, close to 90%, if they have similar efficacy and safety, but in every 3-month dose. So it shows the value of that dosing proposition. And then secondarily, we will build share, not just with switches, but with biologic-naive patients. So again, only a 10% biologic penetration in the AD space. Meaning that we have loads of patients that are on topicals that haven't made that transition yet, that are much more likely to make that transition to a quarterly dosed option.

In fact, market research shows that they are 3x more likely to move toward 777 quarterly dose option than DUPIXENT every 2-week injections.

Patients want to take the drug and then not think about their disease. And that's what every 3 and 6 months will provide in addition to all these other features.

I know you guys haven't -- you talked about Phase III at a high level, but is that kind of the thought that 20% would be biologic experience also in the Phase III? Or you haven't quite like...

We haven't quite finalized what that's going to look like, but yes, we would expect to have biologic experienced. It's a pretty straightforward path laid out by the FDA. We will need to replicate Phase III trials versus placebo. Companies often will then do a third trial with TCS to make sure that it's part of the label.

And then on Part B, you have also mentioned that you're going to test higher doses, higher exposure levels. Maybe talk about like the efficacy or other profile that you could see with higher dose levels and whether there is like a ceiling that you could reach with...

Yes. Maybe I'll start with this one. I think it's the right experiment to conduct right, is to increase exposure just as we're doing in Part B, right? We already had higher exposures than Ebglyss in Part A. We're going to increase those exposures or we have increased those exposures in Part B and the data -- it's the right experiment to do. The data will come back. Here's -- I'll reiterate a point I made earlier. We do not need higher efficacy to win in this market and become the most preferred product. So anything that comes back to us from Part B higher exposures is complete and true upside for the product.

And remember, of course, we do need to test that lower range of efficacy dose for our conversations with the FDA which we expect to have before the end of '26 so that we're prepared to start our Phase IIIs by the end of '26.

Let's switch to -- sticking with 777, but asthma and beyond. So maybe give us some context for biologic penetration there? And then maybe what -- in the Phase Ib, which is, I guess, early part of next year, like what -- how are you guys thinking about that, how that could play out from a headline perspective?

Absolutely. So our Phase Ib asthma in Q1, we selected it as our first expansion indication because there is an approximate 30% overlap between AD and asthma patients. And for DUPIXENT, it's the second revenue driver after atopic dermatitis. For our data in Q1, we're looking at a FeNO readout, where we're looking to have a similar reduction in FeNO in terms of parts per billion of 15 to 20. Lebri was lower in the 10 to 15 range. And so for us, a win is to have that 15 to 20. We look at FeNO as an endpoint because it's a good surrogate marker for what we would look at in later trials, which is exacerbation. And then our plan is to take this data from the Ib trial, along with the dosing data we get from our Phase II Part B and then start a Phase II trial in asthma later in the year.

Got you. And the biologic penetration as a comp, I know lebri just launched more or less, but is there a Dupi ceiling, I guess, on the utilization?

For asthma?

Yes.

Yes. No, it's -- again, these are relatively new compared to think about the more mature I&I markets like an RA or an IBD that's closer to 60% penetration. So there is an incredible amount of runway available for asthma. And it is a large market. It's not the size of AD, but it is a large and growing market. And we expect, to Jane's point, our first expansion to go there for a number of reasons. We think that the [out word] already is going to be in the allergist offices anyways. So it's a nice secondary indication for us, and it is growing. Now AD is growing at about 25% a year right now, year-to-date. So -- and again, a little bit lower biologic penetration.

But the reality is both of these indications have -- we're scratching the surface on, lots of runway from a biologic penetration. And they continue to grow year in and year out.

And as we look at the mono therapy, there is for asthma patients that we've seen in DUPIXENT is a type 2 driver, right? So we will be looking at a subset of the patient population that is EOS greater than 150, which would be consistent. So how do we then break through an efficacy ceiling? It's done through a combination, similar story that we had for atopic dermatitis, for respiratory. We're looking to combine IL-13 with our TSLP antibody to see if we can get a higher efficacy potentially across a patient population.

So you wouldn't do monotherapy, you would do the doublet, you think, if you look to, say, COPD or you think that -- would that be a better approach outside of AD?

We will take forward a mono and then we will follow up with a combo approach, so very similar. We want to be a serial innovator particularly in AD. So we will launch with mono therapy and follow with the combo 279 and then the same in the respiratory. We will launch with a mono for asthma and then look to follow up with the combination.

Okay. Makes sense.

And for [Technical Difficulty] what kind of cost reduction that you're seeing?

We have a clear bar. Anything below 15 would be a failure for us. And so we're looking for 15 and above, similar to Dupi in terms of parts per billion reduction.

Let's say, it's around like 13, 14 , would you still use it as a combo therapy like or do not proceed with the program?

For the combo, there's a few different things that we want to see. Right now, Lunsekimig, which is their IL-13 TSLP nanobody. We'll have data in '26, including asthma in the first half. That data will help inform how we're going to take forward a combo in addition to our IB mono data.

I know for DUPIXENT, COPD is the newer indication versus asthma. There are some similarities and some differences on pathophysiology, how are you thinking about COPD in addition to asthma and then beyond looking to say IBD indications, et cetera?

So as you point out, there's different drivers of the disease, right? COPD could have more diverse drivers disease. What we like with the combo is you're addressing both central drivers as well as local drivers of disease. So we think that could be important whether it's asthma or whether it's COPD. Anything to add from the market point of view? I mean, certainly, the unmet need in COPD, right? That is meaningful to what we see as to why we would take that forward in there in addition to asthma.

It's just opportunity, right? It's -- each one of these markets are underpenetrated when it comes to the biologics. COPD, you're really dealing more with pulmonologists versus asthma, could be pulmonologists, but high level in the allergist office, it's also dealing with AD. So it really allows us with our first expansion to unlock the entire opportunity within AD, while also increasing our footing with asthma and then in time, just as we saw Sanofi and Regeneron do, you can look to move into COPD and other disease states.

Yes. Makes sense.

[Technical Difficulty] can kind of pivot to combo strategy, so next year, you're going to be [indiscernible] and you running head-to-head trial against you. So if we talk -- talk to us about the confidence you have in the combo and then you have kind of a bold move to compare against Dupi, your expectation in terms of it?

So we chose the combination of 777 and 990, which is our 279 co-formulation because of the orthogonal mechanisms, right? IL-13 has that deep type 2 inhibition that you see across all AD patients. Where you see heterogeneity is where the Type 1 and the Type 3 inflammation contributes. And OX40 ligand as we've seen with Sanofi's and [indiscernible] has that breadth of type 1, 2 and 3 inhibition, but not the depth on type 2. So by combining the two, we hope to see a greater efficacy than we see with DUPIXENT.

So what kind of greater efficacy? We're looking for 8 to 10 points greater efficacy on any of the end points whether it's EASI-75. So we're bringing more patients up to that level or the deeper end points, IgA-01 and EASI-90. So that trial, as you noted, reads out in the second half of '26. It is designed to provide a signal with the total patients of 50. And then from there, we'll determine a Phase II trial and the contribution of parts that we would need for a Phase II.

But the goal is to get in efficacy that is more similar to JAK's, but without the safety concerns, which terms don't want to deal with labs with JAK's and the concerns that come with that class of drugs. In our preclinical trials of this combination, we do not see any signal on the safety side. So we'll have to prove that out in this Phase Ib head-to-head.

And then I know for keeping on the combo conversation regarding the -- your 333 and 273 combo in the asthma. And you mentioned you are waiting for the competitive readout in the first half. What specific like efficacy or safety signals you are looking at from the readout that will inform you on your own, like development of the program?

Yes, certainly, the exacerbation rates, right, and are those greater than what is being seen with Tezspire and others. So that's what we're going to look at and use that information combined with our own data to date.

As you look to the combo, the 279 combo, are there inflammation biomarkers that maybe could predict where you could go next from like atopic dermis here and asthma COPD or IBD or here that you could maybe fine-tune the indications that you could go after? Or are you just looking at it, like let's get the first set of the data and then we'll kind of move from there?

We're pretty focused for 279 on atopic dermatitis, right? And so I think the data and the additional biomarkers, et cetera, will inform us what if. But the priority is to determine the next steps to bring that is our second franchise, our serial innovation in AD for atopic dermatitis, right? So that is the foundation of the company. We want to be a serial innovator in atopic dermatitis like you've seen with the success of Vertex or Gilead, constantly improve upon ourselves in addition to the pipeline and a product potential that we see with 777 as a franchise.

Okay. That makes sense. It's funny because a lot of the more mature legacy franchises have into things like HS and the nasal polyps like all the many other indications, but it definitely is well after they established atopic derm or respiratory as like the foundational, I think. So maybe they didn't have as many growth opportunities there, but you have to be in it in the core indication first, obviously.

And we have a path that's very well established, right? What DUPIXENT has done is determined that the efficacious dose in Phase II for a therapeutic category and then for additional expansions within derm, within respiratory, within EOE, they go straight to a Phase III. So that's very well established in terms of the pipeline and a product opportunity.

Each of these indications can be and many are already blockbuster status for DUPIXENT, right? The difference is if you look at their overall revenue, the majority comes from AD and the biggest opportunity. It's not just the largest market. It's the fastest-growing market and the least penetrated. We think that by 2040, this could be a $50 billion biologic market. So does it make sense to expand? Absolutely. But to your point, Geoff, I think it makes good sense to start with your largest opportunity, and we see significant differentiation in that space.

And then looking at bigger picture in terms of like a commercial landscape, your drug would launch in '29 or around that timeframe. And given the strong performance of Ebglyss, Nimluvio commercial launch, how do you think the kind of market segment could look like by that time and when 777 potentially launches?

Yes, thanks for the question. I think, first, I would say, we are really encouraged by the recent launches. Nimluvio is annualizing at about $500 million a year right now. Ebglyss is annualizing at about $650 million a year, both right in their first year of launch. And what's really interesting, going back to the point of the size of this market is they're doing that well without much differentiation and they're doing that well as DUPIXENT continues to grow and have its best quarters. So the market as a whole is growing at 25%. The new-to-brand prescriptions are growing at 49% right now in this space.

So we expect that the market continues to grow, continues to move patients from topicals over. We believe that both physicians and patients have a high expectation around dosing options in this space just as they've been given in other I&I indications, like plaque psoriasis. So we think that if you look at our market research, if you look at this product profile, when you can bring forward a product that impacts EASI-75, we've had the highest -- as a reminder, we had the highest in IIa highest absolute and placebo-adjusted EASI-75 scores of any biologic. We now have this rapid itch relief that you get with Nimluvio in that first 48 hours, and we're bringing forward what both physicians and patients want quarterly and semiannual dosing.

So we expect that the market evolves, but we also expect that we are a first-line agent, and we are the most preferred product by physicians and patients.

And in terms of securing kind of payer access, I mean, these drugs were able to get good access at the onset of like launch. How do you see like 777 kind of being able to get favorable access considering there will be other drugs in the market at that time as well?

Yes, I've had a number of questions on access in the last year, and I continuously say that the AD market, it needs new options. And what I mean by that is, right now, so you think about DUPIXENT, only one out of every two patients is going to reach an EASI-75, 50% of patients discontinue within the first 2 years. Patients will be moving. It's -- this is not a winner-take-all market. It's not a one and done, similar to plaque psoriasis. There are 8 products in plaque psoriasis that do north of $2 billion a year.

I mean, the clear winner is the quarterly dose SKYRIZI, right? But 8 products doing that. Why is that? It's because patients need options. If something is not working or you have a side effect or whatever the case may be, you need to move to something else. If you're a payer, and this is why I said before, and it's -- you can see the reality, both Ebglyss and Nimluvio have a really strong commercial access, 80% and 90% commercial access. Because as patients move from one product to the next, if it is not covered by a payer, then that payer (sic) [patient] is paying full list price.

When you have that many patients that aren't getting what they need today, even whenever we come to market, two out of every three patients are reaching EASI-75. There's still going to be a portion of those patients that may need something more. So we have the highest confidence level that we will get first-line access. Payers pay for products that will be used. There's not a product in the AD biologics space, more preferred by physicians and patients. In fact, we had a market research done recently, looking at our Part A profile versus all of the other products in the market and just simply asked physicians to force rank what product they would use first through fifth, what's the #1 biologic? 60% of physicians said with your IIA product profile, this is our #1 product. So it will be used if it's going to be used, it needs to have contracted access in that first line space.

I guess just a last question to follow on Nishant's is when you think about the overall sort of commercial strategy, is there something that you can do in Phase III to maybe help you with the -- maybe a new onset with either differentiation with payers or physicians that can maybe give you a bit of a leg up as you think about like formulary discussions and negotiation?

Yes. I think -- yes, there's quite a bit that we're learning from conversations with payers, market research and one-on-one conversations. And one of the reasons that we've created our commercial team here at Apogee so early is to ensure that we have that dialogue, that open dialogue with payers. We're looking at ensuring that our Phase III program includes what's important, not just for the disease state physicians and patients but also payers for access.

And there are a number of things that we are including. But I'll tell you, like, for example, the quarterly and semiannual dose to really push both that early gives us that advantage to bring forward an auto-injector and a prefilled syringe at launch gives us that advantage. Most have not done that, frankly. So there's a number of things that we're learning to ensure that the most amount of patients early on can be prescribed, get the product, it pings the payer. They see the value early and the more they see that, the more they know that they need to have access for patients.

Awesome Jeff, thank you so much. Great conversation.

Perfect. Appreciate it.

Thank you so much.