ATI-052 Phase 1b POC Results Update - ACLARIS THERAPEUTICS INC

Hello, and welcome to the ATI-052 Phase 1B POC Results Update. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star-1-1 on your telephone. You will then hear an automated message advising your hand has been raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. It is now my pleasure to introduce Head of Communications, Will Roberts. Thanks, Andrew. Good morning, everyone, and welcome to the Eclair's Therapeutics Conference Call to review the positive primary analysis results from our ATIO5-2 Phase 1B proof-of-concept trials in asthma and atopic dermatitis. The press release on these clinical results was issued this morning and can be found in the press releases subpage of the investor section of our corporate website, eclairstx.com. Please note that we've provided slides as a part of this discussion, and they're now available in the webcast window and as a downloadable PDF document on our website. We'll reference the slide numbers throughout. A Q&A session will follow the prepared remarks. Before we begin, I'd like to remind you that today's webcast contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements represent management's judgment as of today and may involve risk and uncertainties that could cause actual results to differ materially from those expressed in or implied by these statements. For more information on such risk and uncertainty, please refer to our filings with the SEC, which are available from the SEC and on our corporate website. Any forward-looking statements represent our views as of Today, October 27, 2026. Joining me on the call are our CEO, Neil Walker, Jesse Hall, our Chief Medical Officer, Roland Kolbeck, our chief scientific officer, and Dr. Michael Cameron from the Department of Dermatology at Mount Sinai in New York, and an investigator in our atopic dermatitis trial. Hugh Davis, our President and Chief Operating Officer, and Kevin Balthasar, our Chief Financial Officer, will also be available for questions following the prepared comments. And with that, I'll turn the call over to Neil. Thank you, Will. We are pleased to report that ATI-052 showed strong proof of concept in both atopic dermatitis and asthma. These results also demonstrate the art of the possible with a bispecific antibody, showing that one compound may be able to provide not only rapid response, but also a broad response across indications and across diverse patient populations. They help validate the potential additivity or synergy of a dual mechanism targeting T-slip and IL-4R, and as such, provide the compelling proof of concept we wanted to see. ATI-052 was well-tolerated with no conjunctivitis, and the efficacy signals emerged early and were consistent with the biology ATI 052 was designed to treat. As you see on slide 4, ATI052 targets type 2 inflammation at two important points in the pathway. T-slip is an upstream signal that helps start and amplify the inflammatory response, while IL-4 and IL-13 are key downstream signals that drive many of the manifestations of type 2 disease. Importantly, these pathways are relevant to the clinical features we are ultimately trying to improve. In atopic dermatitis, that includes itch and overall disease severity, and in asthma, inflammation that can impair lung function. ATI-052 combined those two mechanisms in a single molecule, blocking T-slip upstream and IL-4 and IL13 signaling downstream through the shared IL-IV-R receptor. The binding interface is multi-paratopic, designed to deliver best-in-class potency and long target retention. A YTE mutation extends half-life, supporting less frequent and dosing. The goal is to achieve additivity or synergy of hitting both targets for broader control of the inflammatory response and ultimately greater impact on disease. A couple of contextual comments before getting into the results. Slide 5 helps clarify the importance of blocking IL-4, a question we often get, which ATI-052 does through its shared IL-4R receptor with IL-13. IL-3R as a mechanism is approved across five indications, and because it blocks both IL-5 and IL-14, it covers the biology that drives asthma and other TH2 diseases. By contrast, IL-15 selective antibodies are thus far 0 for 8 in late-stage asthma and eosinophilic esophagitis programs, so blocking IL-16 alone hasn't been enough to match dupilumab, which is an IL-4R blocker. T-SLIP adds complementary validation in EOE, asthma, and CRS with NP, and we believe will be validated in AD. That's the reason we believe blocking both targets in a single molecule has the potential to deliver a broader and deeper response across many indications. For additional context, an important point regarding severity and atopic dermatitis as described on slide six. When looking at atopic dermatitis data, not all patient populations are equal. There are two ways to look at severity, EZ over 21 and IGA4 status. IGA 4 is more reliable in dictating severity by largely taking its stent out of the equation. Patients who begin with more severe disease, like an IGA-4, for a variety of reasons, have further to go to reach the same clinical endpoint than more moderate patients like IgA3. One can clearly see that the dupilumab and leberkizumab data illustrate this well with stark differences between IgA-3 and IgA4 response even at week 16. It is clear that baseline severity should be taken into account when interpreting efficacy results from a given clinical trial. The next couple of slides show the results we'll cover in detail shortly. with atopic dermatitis, we conducted this trial in a difficult-to-treat, severe, and diverse population. 78% of patients had a baseline IgA of 4. As you'll hear from Jesse, this is important as patients with severe AD have a higher baseline disease burden and therefore need a greater absolute improvement to achieve the same clinical endpoints as patients with moderate disease. At day 57, or week 8, after five weekly loading doses, ending at week four, we saw meaningful placebo-adjusted reductions from baseline in EZ and PPNRS. As Jesse will describe later, we also saw an encouraging early indication of durability in atopic dermatitis with maintenance of response through week 16 or 12 weeks after the last load in dose in a severe patient population. And in the skin, we see a pronounced reduction of established dupilumab biomarkers like TH17 and TH2 endotypes, while also potently suppressing the TH1 inflammatory endotype. Finally, we also saw complete normalization of the skin proteome. These tape strips analyses performed by Dr. Emma Gutman's lab at Mount Sinai only increase our confidence in ATI-052, the role of T-slip, and the underlying biologic rationale. now. With asthma, we saw similarly strong results shown on slide 8. These were heterogeneous patients with mild to moderate disease, including inclusion of high and low baseline FEV1, who received a single dose of ATI052. The results demonstrated that these patients improved broadly and rapidly as measured by FENO and FEV 1, with maximum improvement occurring in only two weeks. And in patients that have low lung function that meet a typical Phase IIb inclusion criteria, FEV1 demonstrated potential best-in-class improvements. The remainder of today's call will be as follows. First, Jesse will discuss the safety and efficacy results for the AD trial, followed by Roland, who will highlight the PD biomarker work. Dr. Michael Cameron will then join us to provide his thoughts on the AD market, treatment gaps, his experience with ATI-052 as an investigator in this trial. Jesse will then return to discuss the results in asthma. And then finally, I'll be back at the end to conclude the call. I'll turn the call over to Jesse. Jesse? Thanks, Neil. And good morning, everyone. I share Neil's excitement about these strong results in both trials. As Neil said, ATI052 achieved proof of concept in AD with robust improvements in the extent and severity of disease, as well as in in a broad and diverse population. This study evaluated a load-in dose format of five weekly doses of 480 milligrams of ATI-052 or matched placebo over a 29-day interval. We enrolled 14 AD patients, randomized approximately three to one, and we followed them through day 57 or week eight. The data we're presenting today reflect everything available once all patients completed their week eight visit. Patients then continued an additional 12 weeks for a total of 16 weeks of follow-up. There was no additional treatment provided after week four. As Neil mentioned, we targeted a severe population requiring a baseline EZ score greater than 21. The study was conducted at multiple sites in the U.S. The primary endpoint was safety and tolerability, and we also evaluated efficacy using standard AD measures, including EASY and PPNRS. I want to emphasize the work we did to identify a severe patient population. At screening, every enrolled subject had standardized full body and primary lesion photographs taken, and those photographs went through central review by a dermatologist. The review helped ensure that each subject had the disease based on the target lesion and the extent of disease was consistent with the eligibility criteria. Turning to baseline characteristics on slide 11, we enrolled a diverse range of patients. A high proportion had severe disease, 82% or IgA4. We also enrolled a high percentage of Black or African American and Asian subjects whose disease may have a greater Th17 and Th1 component. These patients are typically harder to treat with Th2-directed approaches alone, given their underlying pathophysiology. It is also more difficult to detect improvement in the erythema component of EZ in patients with darker pigmented skin. Late-stage AD studies typically enroll 35% to 40% IGA4 patients and a higher proportion of white patients than we did here, and we would expect our Phase IIb program to look more like that. To summarize, this was a diverse and difficult-to-treat population. Now the analysis populations. All 14 subjects are included in the safety analysis. For efficacy, we will focus on the per-protocol population, which was defined prior to unblinding. In the active arm, two subjects were excluded. One received only two doses, though that patient responded very well with an 81% improvement in EZ from baseline. The other did not meet eligibility criteria. Two placebo patients went on rescue medication early on and were also excluded. That is illustrative of the severity and extent of disease in this study. Two of the three placebo subjects required rescue medication compared with none of the active subjects. Safety and tolerability exceeded our expectations. As you can see on slide 12, and we're very pleased with the result. There were no SAEs, no grade three or four events, and no discontinuations due to AEs. There were only three injection site reactions, all transient, and most were grade 1. And importantly, something that is beginning to differentiate this molecule, we have seen no cases of conjunctivitis in this study, nor in any of our other clinical studies to date. Looking at efficacy on slide 13, easy improvement from baseline was our key exploratory efficacy assessment. At week eight, we saw a 45% placebo-adjusted improvement from baseline, and that improvement continued through week 10. These are encouraging numbers, particularly given that this severe population only received loading doses. We also saw maintenance of response at week 16, 12 weeks after the last loading dose, which speaks to the potential for durability. And as Neil mentioned, severity matters. As you'd expect, in the IgA3 group, a more moderate population shown on the right side of the slide, we saw even greater reductions in EASY. Slide 14 provides additional context for our Week 8 EASy results, alongside published data from other biologics in AD. Neil highlighted earlier, please keep in mind the differences in baseline severity between studies. With that caveat, our early data compare well to the landscape. Other trials are different and we have not controlled for those differences. On slide 15, 78% of subjects who received ATI-052 achieved EZ-50 at week 8. Of those, among IGA-3 patients, 100% achieved EZA-50 versus 71% in the most severe IgA4 group, again highlighting that more moderate patients are easier to treat. And 89% of ATI052 patients achieved EZ50 at some point during the study, which speaks to the breadth of response across this spectrum of patients. The other key outcome for this population is itch, which is shown on slide 16. Itch is a major component of this disease, so demonstrating a robust reduction in itch alongside the reduction in EZ is important. We know TSLP plays a role in driving itch, and Roland will share biomarker data that explore that relationship further. We saw a rapid reduction in age as early as week one, and a robust absolute and placebo-adjusted 40% improvement from baseline at week four, which was maintained through at least week 10. At week 8 specifically, patients on ATI-052 had a 43% placebo-adjusted mean improvement in itch from baseline. We've also included data from other biologics to provide context on the PPNRS placebo- adjusted response at week 8. On slide 17, at week eight, 33% of ATI 052 patients achieved a four-point or greater improvement in itch from baseline known as ppnrs4 again we've included data from other biologics for context on slide 18 we want to show you visual examples of disease improvement in patients with ati o52 these were selected as illustrative examples the first patient had an iga three at baseline with significant disease on the back of the neck. This was Dr. Cameron's subject, who you'll hear from shortly. The baseline photo on the left shows erythema, scaling, and lichenification. By week eight, the disease had almost completely cleared. Below that is a second patient with severe disease, IgA4 at baseline. The first photo shows significant erythema. Those red areas are where the patient has been scratching, which excoriates the skin and causes bleeding. On the right, by week eight, the eryθema has substantially improved, and there is a small patch of residual lichenification. These week eight results leave us encouraged about the potential for further improvement with longer treatment. So these are two illustrative examples of difficult-to-treat skin disease where ATI-052 made a meaningful difference. Now I'll turn the call over to Roland to discuss the pharmacodynamic results in AD. Roland? Thanks, Jesse. I'm glad to be here this morning to discuss the pharmacodynamics markers we investigated in this trial. The clinical efficacy data Jesse presented are supported by pronounced changes in the skin proteome and in key systemic biomarkers. In collaboration with Dr. Emma Gutmann's laboratory at Mount Sinai, we collected tape strips from lesional and non-lesional skin at baseline and week 8 and analyzed more than 300 proteins using O-Link proteomics. We also evaluated endogenous serum biomarker, including CCL17 or TARG, IL-5, and biladiocinophils. Together, these analyses provide evidence of the broad biological activity of ATI-052 and the potential additivity or synergy of simultaneously targeting IL-4 receptor alpha and T-slip. Slide 19 summarizes the pharmacodynamic profile. We observed broad pathway modulation across Th1, Th2, Th17, and Th22, fibrosis, and itch-associated biology. We also saw an almost complete normalization of the lesional skin proteome at week 8, with the treated lesional profile coming to closely resemble non-lesional skin. This included pronounced reductions in established biomarkers modulated by dupilumab. together with additional suppression of TH1 biology. These results are consistent with the combined activity expected from targeting both T-slip and alpha receptor alpha. On slide 20, the heat map visually shows the skin proteome changes. At baseline, lesional skin was clearly distinct from non-lesional skin. At week 8, the lesional skin of patients treated with ATI-052 shifted toward a pattern that closely resembled non-lesional skin, whereas the lesinal profile in the placebo group remained comparatively similar to baseline. Quantitatively, ATI 052 produced a 95% overall improvement in the lesion versus non-liesional proteome relationship by week 8. For context, the published dupilumab dataset shown on the slide reported a 66% improvement by week 16. The depth of normalization observed with ATI-052 supports the potential for additive or synergistic biological activity from dual IL-4 receptor alpha and T-slip inhibition. Slide 21 examines the breadth of that response in more detail. Gene set variation analysis showed downregulation of Th1, Th2, Th17, and Th22, and pruritus-associated signatures in lesional skin. The slide includes representative mediators within these signatures. I want to particularly highlight the reductions in the Th1-associate markers CxCl9 and CxCl10, which are not modulated by all four receptor alpha blockade alone. This broad pathway modulation is consistent with the contribution of T-slip inhibition to the dual mechanism of ATI-052. The systemic biomarker data tell a very consistent story with what we saw in the skin. I would particularly highlight the reductions in IL-5 and peripheral eosinophils with ATI which are consistent with inhibition of the T-slip pathway and differentiate ATI-052 from alpha-receptor alpha blockade alone. With dopilumab, IL-5 is not reduced, and peripheral eosinophils can transiently increase. So when we look across both the skin and blood, we see broad and deep pathway modulation that is consistent with engagement of both components of ATI-052. The point specifically about T-SLIP, the question we have received often is whether T-SLIP has an important role in atopic dermatitis. The ATI 052 results add to the emerging evidence. We observed clinical activity in a patient population enriched for severity together with broad modulation of Th1, Th2, and Th17 and Th2 biology, marked normalization of deletional skin proteome and reductions in L5 and eosinophils. These findings support the role for T-slip in the broader inflammatory biology of AD. In summary, this trial evaluated load-in doses without any maintenance regime. ATL-052 achieved the safety, tolerability, and clinical efficacy of T-SLIP. The dynamic results support the proposed dual mechanism and provide evidence of the potential additivity or synergy of targeting T-slit together with L4 receptor alpha. We believe ATI-052 molecule potential applicability across type 2 diseases. With that, I'll turn the call over to Dr. Michael Cameron, Assistant Clinical Professor in the Department of Dermatology at Mount Sinai, for his thoughts on the market opportunity and his experience with ATI-052. Dr. Cameron? Dr. Well, thanks, Roland, and thank you, Claris, for involving me in this conversation. As I mentioned, I had the esteemed opportunity to be involved in this clinical trial and see some of my patients really benefit from it. And, you know, as has been discussed, there's a lot of mechanisms of action in the pipeline for atopic dermatitis. But really, this is a massive, massive market that's growing year over year. And unfortunately, we have not seen much movement in terms of increased efficacy in our commercially available therapies. You look at dapilumab, Depixent, which has been out for close to 10 years. And the primary endpoint, you know, around 37, 40% getting, you Know, an IGA response, you Know, 48, 50, 55% getting an easy 75 response, non placebo adjusted, we haven't really seen incrementally much movement from there. And the vast majority of my patients that are on Depixit are either partial responders have a tolerability issue, or lose response over time. And so there's just a massive need for new mechanisms of action. We look at all the different endotypes of atopic dermatitis, and it really is driving that need. Not only do we need things with higher bar efficacy, both in terms of skin clearance and itch relief, but we need new MOAs to target those various endotypes. So that really is what makes me excited about this the CLARIS asset is we're really excited about bispecifics just because you are not only going to target exclusively the Th2 pathway, you're going to introduce, for an example here, T-slip, which is a really important peritogen for atopic dermatitis. And that's what I saw with my patients was you're getting that skin clearance via the IL-4 receptor inhibition, but you're also getting really immediate itch relief and additional anti-inflammatory effect by targeting T-slip. And so I had a patient that was actually presented in this slide deck. That was my patient, and she had been through numerous previous biologics, and she had a very rapid and very, very deep skin clearance and itch relief with this IP. And interestingly enough, close to a half year out, even while off therapy, she continued to have a very, very durable response and almost a remittive effect. And so that really gets me excited about this asset. And I think, you know, more and more mechanisms of action are going to be needed over time. And that's what gets me excited about the bispecific. So for me, in terms of looking at atopic dermatitis as a whole, like what are the big gaps? Obviously, we want an oral medication that does not require lab monitoring, that is going to have dupy-like efficacy or better, ideally. But in addition to that, I'm seeing for my patients that more and more patients want injectables as opposed to orals. I think that Wall Street and investors often think that oral is better. And I don't think that's necessarily the case. I mean, we've seen that with the TIK2 inhibitors and psoriasis and throughout the immunology space. And I think the innovation behind the GLP-1s and the tens of millions of Americans who are taking GLP1s has gotten even more and more people comfortable with injectable medications. I think dermatologists have a lot of prescriber inertia and they oftentimes, they get used to one way of doing things and they've gotten used to providing their patients for atopic dermatitis with biologics, with injectables. And so that's what really gets me excited about something like this asset where we can, you know, potentially raise the bar in terms of onset of action for itch relief and skin clearance, and we can target more potential endotypes for atopic dermatitis. So, thank you again, Claris, for involving me in this trial, and I'm really excited to hopefully be involved in the phase two trial as well. Thanks, Dr. Cameron, and thank you for all you do for patients with this disease. Now on to the asthma results. The short version is that this was another trial with encouraging results. After a single dose of ATI-052, patients responded rapidly. We saw changes in pheno, a marker of airway inflammation, and in lung function within the first two weeks. The speed and breadth of that response gives us confidence in this molecule's potential in asthma. As you can see on slide 23, we enrolled 16 patients and randomized them three to one. This was a single injection at baseline. Active subjects received a single 480 milligram dose of ATI-052, and the others received matched placebo. The assessment period was 29 days, followed by an additional six-week follow-up period for a total of 10 weeks of follow-ups. The majority of sites were in the U.S. with two sites in Germany. The primary endpoint was safety and tolerability. We also evaluated key efficacy measures that matter for asthma patients, including pheno reduction and FEV1 improvement. Slide 24 shows the patient population. To be eligible, patients needed a baseline pheno of at least 35 parts per billion. For eosinophils, eligibility required a current or historical eosinophil count to be at or above 150 cells per microliter. Interestingly, the population included subjects with eosinfils less than 300 cells per microliter, a population of patients for whom the benefit is smaller with dupilumab compared to those with an eosinofilic phenotype above 300. The other point I'd like to highlight is baseline FEV1. We set a minimum of 60% of predicted, but no maximum. As a result, half of the enrolled subjects had a normal FEV1, so the improvements I'll show were achieved in patients with limited room for improvement. In a more typical phase 2b or phase 3 population, FEV2 bounds are typically set up to 80%, so patients with considerably more room for movement in lung function. Turning to safety on slide 25, HEI 052 was well tolerated, consistent with the AD study and the healthy volunteer study. There were no SAEs in any patient. There was a single treatment-related adverse event in the 052 group, a mild injection site reaction. And consistent with the rest of the program, we observed no conjunctivitis. Now to phenosuppression on slide 26. This highlights the rapidity and breadth of response to ATI-052. Patients who received a single dose of ATI 052 experienced a 59% reduction in phenol from baseline, an absolute reduction of 45 parts per billion. Our goal going into the study was about a 40% reduction, with 50% representing a particularly strong result. Given the 59% reduction, we were pleased with both the magnitude and the speed of the response. On slide 27, we've included published dupilumab and tesopilumib phenodata to illustrate the broader treatment landscape. Slide 28 shows responses in the subset of patients with eosinophils below and at or above 300 cells per microliter. This threshold is commonly used as a marker of type 2 inflammation, and dupilumab has shown benefit in clinical trials in eosinophilic phenotypes above 300 sales per microliters. At day 15, we observed a 58% reduction in pheno among patients with fewer than 300 eosinophils, and a similar 60% reduction among those at or above 300. That is a consistent response in both groups, which speaks to the breadth of response in this study. Also at day 15, looking at another outcome measure for disease improvement, 58% of ATI052 patients reached a pheno at or below 25 parts per billion, a level generally considered normal. We also saw FEV1 improvement in both eosinophil subgroups. On slide 29, we show FEV2 results. At day 15, we observed a placebo-adjusted improvement of 200 microliters, which increased to 260 microlitters at day 29. As a reminder, we enrolled patients who generally had normal FEV3, meaning at or above 80% of predictive. On the right is a post-hoc exploratory analysis of the subset of ATI-052 patients with baseline FEV1 below 80%, which is more typical of a Phase IIb population. In this subset, active patients improved by an absolute 350 mLs at day 15 compared with a 140 mL worsening among placebo patients. On slide 30, we show the absolute and placebo-adjusted FEV1 change in that subset alongside published data for context. Finally, slide 31 shows an outcome from oscillometry, which measures resistance in the large and small airways. The small airwaves matter most in asthma, and particularly for exacerbations. Patients with severe small airway disease are at substantially higher risk of exacerbation. In the same subset of ATI-052 patients as on the prior two slides, we saw a reduction in small airway resistance consistent with improved small airwave function. This is the kind of signal you want to see in a POC trial in patients with asthma. So to bring this together, a single dose of ATA-051 was well tolerated with a safety profile consistent with the AD trial. We saw rapid responses in both PHENO and FEV1 with benefit visible at the earliest time point measure, and the response was consistent across a heterogeneous population, including both eosinophil high and eosinfil low patients. I'll turn the call back over to Neil for some concluding comments. Neil? Thank you, Jesse, and thanks, everybody. The POC data gave us several key learnings. We saw signs of additivity and synergy across clinical and PD measures, along with breadth and depth of response, activity against all three inflammatory endotypes in severe atopic dermatitis, and improvements in both FENO and FEV1 in T2 high and T2 low asthma patients. In atopic dermatitis we saw strong evidence of T-slip involvement, including complete normalization of the skin proteome and reductions in IL-5 and eosinophils. Early durability in atopic dermatitis was encouraging, with responses maintained through at least week 16 so far. Tolerability has also been strong and potentially differentiated, with no conjunctivitis seen to date. Overall, we see a real opportunity to raise the efficacy ceiling for patients with type 2 diseases. Together, those markets represent hundreds of millions of patients. Having demonstrated these proof-of-concept results, consistent with our development strategy and disciplined capital allocation, we intend to move to Phase IIb, where we will prioritize eosinophilic esophagitis. This is a great opportunity for this molecule for a variety of reasons, including a growing global market, ample open white space, and a strong mechanistic fit for ATI052, given the disease biology and the efficacy demonstrated with targeting IL4R and T-slip alone. We expect to start this study early next year with the intent of designing it as a seamless Phase 2b-3. We are also evaluating the potential for one additional indication, and we'll provide updates shortly. And as promising as these POC results are, this is just the start of the catalyst calendar for us. In addition to the go-forward plan for ATI-052, we expect the top-line data readout from our T-slip MAB-Vosacatug and atopic dermatitis later this quarter, which we hope will further demonstrate the value of T-Slip in AD. We have a slew of catalysts with our oral small molecule program, including monzatinib. As a reminder, we received fast-track designation for this program earlier this year. We expect to kick off the lichen planus trial in the coming couple weeks. Once we have data for 60 percent of patients in the mucosal cohort, we plan to conduct an interim analysis, which is expected later in 27, and if the data are supportive, we plan to engage with the agency regarding the potential to convert into a registrational study as allowed by FASTRAC. And lastly, we expect to file the IND for our ITK inhibitor, ETI 9494, this quarter as well, which will then kick off a series of catalysts in 27. Thank you for your time and your interest. We'll now take your questions. As a reminder, ladies and gentlemen, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, press star 11 again. One moment, please. The first question comes from the line of Byron Amin with Piper Sandler. Yeah, hi, guys. Thanks for taking my questions, and congrats on all the data across both the AD and asthma trials. Maybe to start on the AD studies, how many patients in the AD trial had prior biologics? So that's the first question. And then the second question is, you know, what led you to prioritize EOE for the Phase IIb? And then for the next indication or the second indication of either AD or asthma, what are key considerations that you're thinking about as you choose that second indication for 052? to, and does the data from Bosakitug and AD at all factor into that decision-making? Thanks. Yep. Thank you. Thank You, Barron. Appreciate it. So, in terms of the prior biologic use, we did have about four of the patients in the active group were on previous biologics, including drugs like Lansicomig and some IL-18 inhibitors, and so there is definitely an experienced population that was part of the study. You know, on a percentage basis, that was about 40 percent or so of the active cohort. In terms of prioritizing EOE, you know, I think between the last time we provided an update and getting this data, obviously, tezopelumab generated really strong results in EOEs kind of validating the T-slip side in the pathophysiology of eosinophilic esophagitis. And clearly, you know, knowing that DUPI is approved, this is, again, kind of like asthma, a spot-on mechanistic match, and we obviously believe we have a best-in-class T-SLIP side of that molecule. So I think that is a key consideration. I think the other key consideration is the ability to take an indication all the way to the finish line. And I think EOE is obviously less capital intensive there. Studies are a little bit smaller than asthma or atopic dermatitis. So I think for a small company like us, it makes sense, just like we're doing with LP on the oral small molecule side, to engage in indications that perhaps have a little bit less competitive intensity and that we can take all the way. In terms of the second indication, we're in that evaluation mode. Fortunately, we've done a lot of the work already on all three indications. We're just shifting capital over to EOE. I think in the coming weeks, we'll, you know, both of these studies are ongoing, so we'll collect the remaining amount of data there, and I think you bring up a reasonable point that the efficacy that we saw in AD was, you know, exceeded our expectations, gives us confidence in post-Hackatuck, but we want to see that data read out, and that would certainly, I think, put the final nail in the story of T-slip involvement in AD. So more to come on that, but full steam ahead on EOE. Great. Thanks for taking my questions. Thank you. And our next question comes from the line of Raghuram Selvaraju with AC Wainwright. Thanks very much for taking my questions and congratulations on this data. I wanted to drill down a little further on what you see as a key safety advantage for ATI-052, specifically with respect to dupilumab. And if you believe that based on the mechanism of action of the drug and the profile that you have observed so far, that additional safety advantages for assistive pillinab could emerge beyond the absence of conjunctivitis? Yeah, thanks, Ron, for that question. Appreciate it. It's something that certainly doesn't get asked a lot, and I think as a former practitioner, I'm sensitive to those because all safety issues matter, right? And I think certainly conjunctiva is a key differentiator could emerge as that for us. And, you know, we've seen varying rates, you know, going up as high as 18, 20 percent with other molecules and 10 percent with dupilumab. And we know that with DUPI in general, when you're taking down the Th2 side of the house, that sometimes you get a Th17 skewing and those patients can sometimes get seronegative arthritis. We also know that oftentimes there could be a Th1 skew as well, where you get eruptions of erythema and rash on the head and neck area. So there are some things I think that one has to be mindful of, and maybe the beauty of O5-2 is, as we clearly showed today, you know, we're not just taking the Th2 side down, but we're also firmly compressing Th17 and also roping in Th1. So I really, that was one of the most exciting things to me, is not only do you pick up the heterogeneity piece but importantly as you point out I think you check many boxes on the safety side and with respect to dose and convenience is there some way for us to be able to assess what you ultimately expect to be achievable with 052 that could constitute a sustainable competitive advantage as we all know lots of other folks have attempted so far to demonstrate a profile that would reflect meaningfully improved convenience versus the twice-a-month injection schedule with dupilumab. But, you know, in other contexts, we've seen, you knows, particularly yesterday in psoriasis, the prospect of the possibility of a once-a year dosing, etc. So, what do you think is ultimately achievable here, you know, in between sort of the twice a month and the once a year dosing administration? Yeah, it's a good question. I think everything's kind of indication dependent. You know, psoriasis, as you well know, is a much different market. But, you know, I think from my perspective, again, having practiced for many years, I think quarterly dosing is, to me, a sweet spot when you're managing these eye and eye diseases that tend to vary over time. And certainly there's a lot of room between what you just mentioned twice a month and yearly. So, you know, what we've consistently messaged is that we believe we can get up to quarterly dosing. And, you Know, we're going to test a variety of dosing regimens in our go forward study. And you know there's, as you know in atopic dermatitis as an example, there's induction dosing that usually occurs through 16 weeks and then you go to maintenance. And so, we'll be testing a variety of factors there. But I think, you know, from my perspective, we've always kind of leaned in a lot more on efficacy and certainly believe that dosing interval and convenience is important, but you have to check that first box first. Thank you. Thank you. And our next question comes from the line of Seamus Fernandez with Guggenheim Securities. Oh, thanks for the questions, guys. So just a couple of quick clarifying points. Can you just remind me how many patients were in the final analysis on the placebo side? It's just a little bit unclear in the sort of final analysis how that played out. Second question is, you know, as we think about the EOE opportunity, you know, what is that path forward from phase two to phase three, this sort of seamless approach? When should we anticipate seeing the EoE data? It does, and, you know, I take your point on efficacy with a certainty, but weekly dosing with Dupixent seems like an easy bar to move past for a bispecific in this, in the EOE setting. So, you know, is it kind of an underlying assumption that monthly is kind of a base case for your program in EOEs that offers, you know potential optionality, you you know, to a longer dosing profile in EOE in particular. And then the last question, as it relates to your lichen planus advancement in the next couple of weeks, can you just highlight for us a little bit more of the, you know sort of clinical trial design, specifically the endpoints that will be used in that study, the patient population that you'll be approaching initially, and then what that path, rapid path forward to phase three could include in the lichen planus setting specifically. Thanks so much. Sure. No problem. I think I got all that in my head. So thank you for the questions. I'll answer the EOE first. You're right, Seamus. I Think the bar there is certainly lower. And, you know, Q monthly would be, you Know, at a minimum and obviously strive for greater, but I think it's a little bit easier hurdle on the convenience side in that particular indication. So thank you for bringing that up. On the atopic dermatitis study, so 14 patients in, there were three of those were in the placebo group. Two patients in the placebo group had major protocol violations at day 35, I believe. Both of them were put on high-potency topical corticosteroids, and that basically meant they were out of the analysis because now you're no longer comparing to placebo, you're comparing to high-potency topical steroids. So there was one patient in the placebo group that was going forward from about day 43 or so on. And then on LP, in terms of activities there, we're initiating that study in about two weeks. And so you'll start seeing things on clintrials.gov from us there. On trial design, it's a, as we mentioned in the past. It's a basket study, but we're doing it cohort by cohort. We're going to spend most of our time on mucosal LP, which predominantly will involve the oral area, and that will be a 16-week study endpoint. Primary endpoint will be ODSS, which is the oral disease severity score. We'll also have a variety of other endpoints, including IGA, and then we're going take an interim look when we get about 60% of those patients, 50% to 60% of those patience through week 16, and what we anticipate to see is a pretty rapid response, and if that is the case, then I think what FastTrack allows us to do is to go have some conversations with the agency, and then what we would strive to do, is to convert that particular phenotype into a registrational study, so we're not going to wait for the whole entire basket study to finish. We're going to do it cohort by cohort. So that's, I think, what it looks like, and hopefully that answers your questions. Great. Super helpful. Thank you. Thank you, and our next question comes from the line of Prakhar Argawal with Cantor Fitzgerald. Hi. Thank You so much for taking my questions, and congrats on these datasets. Maybe in the asthma trial, the kinetics of the phenol reduction for the bispecific at day 15 versus day 19 is a bit different than Sanofi's Lensecumib, which targets the T-slip R13 cytokine. So maybe if we can elaborate on why this may be happening and what does it mean from a dosing perspective, especially for the EOE trial as well as we think about induction versus maintenance. Secondly, on lichen planus, Neel, you talked about oral mucosal and ODSS as being the endpoint. Like, what's a good result on that endpoint, and will the trial be powered to show statistical significance given it's a smallish trial? Thank you. Sure. Sure. Thanks for the questions, Prakhar. On the phenokinetics, you know, right out of the gate, we were down to 50, then to 59%, And then at the end, 40 percent, which even when you compare 40 to the rest of the competitive set is still quite strong. And what you're dealing with there is a single-dose kinetics versus multi-dosed kinetics. And we know with this molecule, single dose with TMDD behaves a little bit differently. And we clearly showed in the atopic dermatitis study, we mentioned this a couple times, that We have quite long durability in terms of clinical, both PD and clinical effect. So it is, I think, a loading dose sort of phenomenon there, and we only tested a single dose in that study. On the LP front, on the endpoint, I'll hand that over to Jesse in terms of what we're looking for on ODSS. Jesse? Yeah, thanks, Neil. So just with regards to ODSS and Prakash's question, so that's the primary endpoint that we'll utilize in the oral lichen planus study. So that was something that was originally developed for oral pemphigoid and then subsequently adapted for oral lichens planus. If we look at that score, it's a really nice scoring methodology for these smaller trials in that it's very sensitive to change. So it goes from zero to greater than 116. And you can imagine that you would see a benefit of change in a smaller patient population with a continuous variable such as that. We haven't disclosed externally exactly what we're doing from a goal perspective, but you'll hear more about that in the future. But I would anticipate that that's an excellent outcome measure to evaluate disease change in a small patient population. And our next question comes from the line of Michael King with Rodman and Renshaw. Thanks, guys. Can you hear me? Yes. Thanks, Willie. Sorry for any background noise. Just wanted to ask, again, I also had a question about the demographics of the AD patients. addition to the two dropouts, it looks to me that the O5-2 group was fairly about 10 years younger and also weighed a fair bit less. So I don't know if that had any influence on the outcome. I don' know if Dr. Cameron can, I know he's still on, but if you can talk about whether the heavier patients respond better or worse than lighter patients, younger patients versus somewhat older patients, but I just wonder how you want us to think about that. Yeah, I don't, I can take that, Mike. I don'T think, I mean, certainly overall, if you have a meaningful difference in weight, I suppose that that can help from an exposure standpoint. I DON'T think it was really a factor at all in this study. I mean across all the patients, I MEAN that was the beauty to me of these results is that even in a very severe and diverse population, although small n, there was just a remarkable amount of consistency across the board when you think about, you know, close to 80% of patients getting to an easy 50 level after just a load-in dose and just maintaining that out for so many weeks. I think that's quite remarkable and not necessarily what I expected. So I don't – I really don't think that, you know, Delta played much of a role. All right. Thanks for that. And then is this the last data that we'll see here, or are you going to present this so we can see more about the durability? And I know other questioners have asked about the response rate by prior therapy. Will those kind of details be made public at some point in the future just to get some idea of the pharmacodynamics of O5-2 in AD? Yeah, certainly. So the study, both studies are still ongoing. And so we will provide an update, you know, likely at a medical meeting, you know, in the future. So, you know, stay tuned on that front. Are the patients allowed to go on subsequent therapy after the 12-week follow-up? No. And we haven't had anybody in the active group. That's also, and I'm actually glad you brought that up, but brought that up. We have had zero patients in the active group go on any sort of rescue treatment, which is a testament to the biologic power, right? You know, if you think about the fact that we aren't giving any doses past week four, and we're tracking out quite a long time, and to have nobody, you know, come in on a rescue steroid is pretty impressive. Thanks for taking the questions. Congrats. Thank you. Thank you, and our next question comes from the line of Edward Nash with Canaccord Genuity. Hi, good morning. This is Xinwei on the call for Edward. Thanks for the taking the question and congrats on the data. I have two questions from us. One is on the EOE trial endpoint selection. Could you maybe share your thoughts on the relative importance of the histologic remission versus symptomatic improvement, you know, given the histological response rates that we have seen with 2B, what additional endpoints would you consider to be used in the upcoming Phase 2B study to sort of as a more meaningful measure of the drug differentiation? And then I have another question on the AD advocacy durability. You know, as we have seen the sustained effect of the drug post-dosing, I'm just curious about how you interpret the delayed improvement. Do you believe it reflects a sustained target engagement, or could there be a more, you know, gradual downstream immunological effect? Thank you. Sure. Maybe, Jesse, I'll throw it to you on the EOE, and then I can comment on your AD question. Yeah, absolutely. So, just with regards to endpoints that we're considering for the EoE study, so we think that the histological outcome measure is a very sensitive measure for change, and it provides also a low placebo response. So from a dose range and a dose selection perspective in the Phase IIb portion. We think that that's an excellent outcome measure to evaluate dose response. And then just with regards to the Phase III study, we think the co-primary endpoint that was employed in the tezopelumab program is an effective endpoint to differentiate change, and we'll be proceeding with that endpoint. Neil? Yeah, so on the AD front, you know, I think, you know, whenever you have a much more severe population with lichenification, just think of that as thicker skin. Sometimes it takes a little bit more time, but I would say I was really pleased with the kinetics of the response early on, and I think what you're seeing is just the power of the overall molecule when you think about the T-slip that we've long talked about being potential best-in-class, best retention time, best potency out there. And I think you're seeing the effect of that come into the picture. And once the IL-4, IL-13 finishes its job of tamping down inflammation, the T slip comes into play and just keeps those patients stable. So I think, you know, that's our hypothesis about that. And, you know it's really nice to see that long duration PD effect. And that's not dissimilar to what we've seen in a phase 2A with the T-slip Mab-Bosacatug by itself. We're seeing PD in clinical activity sometimes up to four or five months post. So not surprising at all to us. That's very helpful. Thank you. Thank you. And our next question comes from the line of Roger Song with Jefferies. Great. Thanks for taking the question. So just on the EOE, now we have the TESI and the DUPI, positive results, and then just – can you just comment on what is your target product profile in EOEs in terms of the efficacy, much the benefit you want to see by targeting both target and then maybe safety, and then anything you would say about the baseline influence to the potential efficacy potential in your trial. Thank you. Yeah, maybe I'll start and then, Jesse, you can pile on. But, you know, I think it's a number of things. You know, we think about how we might comp here. You know, we know that, you know, DUPI tends to work a little quicker than TESI. TESA obviously shows a robust response at the end of the day, so putting the two molecules together might give you the advantage of quick activity and then long durability. You know certainly as Seamus had pointed out, I think the dosing interval question is pretty easy as well. And we do believe that what we're seeing, you know, in a couple of these studies, well, the three studies we've conducted so far is that there has to be something going on with the T-slip part and the IL-4R part to make sure that we're not getting things like conjunctivitis. It's just a broader suppression of the immune kind of milieu, and so I think, you know, we ought to see that as well in the EOE population, and I don't know if you saw, there's a recent paper, really interesting, and a one, but a patient on dupilumab for many years that had had a pretty middling response and then was put on Tezi and showed rapid clearance, which just shows kind of the additivity piece there. So, Jesse, do you have any other comments on that? Yeah, I think you covered it quite well. If you just look at the DUPI, the fact that that drug needs to be given on a weekly basis, we certainly have an advantage from a dose inconvenience perspective that we will explore. And then the slow onset of action relative to DUPi with Tezi, we think we have an opportunity there. And I think the fact that you're having to dose so high may speak to the burden of disease in this condition where a dual inhibitor could provide meaningful benefit. Thank you. And our next question comes from the line of Alex Thompson with Stiefel. Hey, great. Congrats on the data, and thanks for taking our question. I guess as a follow-up to the EOE conversation, I guess, you know, it makes sense on sort of the maintenance dosing getting to monthly, but how are you thinking about induction dosing? Do you think you might explore higher doses at induction or more frequent intervals than what you've looked at so far in AD? Thanks. Thanks for the question. No, we don't. In fact, you now, moving forward like on an induction regimen or like a load-in dose perspective, we would be looking at a more standard day zero and then two weeks later. And so that's how we would proceed. Okay, helpful. And then maybe as a follow-up, with this concurrent financing you announced today as well, sort of can you talk through what that gets you in terms of runway, this next set of studies, et cetera? Thanks. Certainly. It allows us to – it's really a top-up financing, you know, $50 million, and it was mainly geared at a couple things. One, you know, as we shift some resources into EOE, it allows us the potential if we choose to do a second indication with the buy specific, which we'll update the market on later. But we obviously got a lot going on across the portfolio and really excited about advancing into LP and, you having some flexibility to step on the gas there mid next year what was important to us and then so essentially it allows us to fully fund um you know eoe maybe another indication there with the buy specific uh fully fund the lp fully fund the the itk uh next gen and then buys us two additional quarters or run runway so our original cash out was end of 28 and now that's mid-year 29. Appreciate it. Thanks, Neil. Sure. Thank you. Our next question comes from the line of Catherine De La Russo with Lifesight Capital. Hi. Good morning, team. Congrats on the update and thanks for taking my question. Another one on dose selection in EOE, we've seen that higher exposures seem to be needed on both the IL-4 receptor alpha side and T-sub side, so how are you thinking about relative levels of target coverage for each arm? Are you kind of aiming to match the exposures associated with Dupuy and Tezi or exceed them? And I guess, like, how did that compare to the regimen tested here in AD? DR. Certainly. Thank you for the question. Jesse and then Roland, if you could comment there. Certainly, yeah. So with the Phase 2B portion of the EOE study, we plan to do a dose range, and we're going to explore a broad dose range in that Phase 2b portion. And then based on that, we will select doses to proceed into the Phase 3. I think there's going to be additional information coming quite soon on the design and doses that we plan to pursue there. And then, Roland? Yeah, actually, I don't have to add much more. I think, like Jesse said, I think we'll dose range and we'll test different doses, and from the data, we'll select the dose going forward with. Great, thank you. Thank you. Thank you, and our next question comes from the line of Thomas Smith with Lyric Partners. Hey, guys. Good morning. Thanks for taking the questions. Let me add my congrats on the nice results here. In AD, just wondering if you could comment a bit more on the deathly responses you're seeing in this really severe patient population, whether easy 75 or 90s or IgA clear, almost clear responses. Could you just help quantify that a bit? And then for Dr. Cameron, if he's still available, This is obviously a really severe AD population in this study. Just wondering how you think these efficacy results would translate in a more moderate to severe population that the company could potentially target in a subsequent phase 2B study. Thanks so much. Yeah. So thanks, Tom. Thanks for the question. So certainly, we did see very nice depth of response. I mean, the Cameron patient that he referenced had, I think, a 90 percent response out of the gait at week three or four. And, you know, and that was not an outlier. And I think if you just look at our data and kind of back into kind of percentages, and as I've mentioned in the past, you know EZ50s are a very good leading indicator of what to expect on things like EZ75. And certainly had patients at that level, no question. We just haven't put out that data yet. Study's not over. So more to come on that front. But I was, that was the other thing I was really impressed by with just a load-in dose to see continued deepening on certain patients out past, you know, week eight and into week 10 and 12, I think was really nice to see. And particularly in a severe patient population. And I think to me, again, cross-trial comparisons are always hard, but when you get IgA4s to this level where it's essentially flipped from what most people do and you see these sort of responses, I think that's what's got me really excited. And the second piece is just the consistency. It wasn't as though you had maybe two hyper-responders and everybody else was kind of anemic. It was just straight up across the board, and just look at the easy 50 number. That tells you everything you need to know. When you have that degree of consistency across diverse patient populations, which is the other major point, and severe, and I get it's small n, but, you know, you have, we have all three endotypes represented in a small study. And that was all, you know, by design. Thank you. And our next question comes from the line of Adam Bogle with Craig House. Great, thank you. Great. Thank you. Congrats, team. Thanks for letting me take some questions here. Just on the EOE trial design in a regulatory way just um the proposed early 2027 ea starts um what at the age feedback you know supports that intended seamless phase 2b3 design and you know which elements there still require agreements and then just um quickly just um how much of the decision to prioritize ut reflects on the advocacy profile emerging from these studies versus the commercial opportunity in the capital requirements there. Thank you. Yeah, I'll answer the second question first. Zero. It's more the capital intensity. And, you know, I think, as I said before, we couldn't be more pleased with the results and the consistency of the results across both asthma, all the different kind of phenotypes and endotypes that we had an impact on, which is exactly what you want to see with this mechanism. So thrilled with the efficacy. It really, you know, becomes a game of capital allocation and how we think about investing across our portfolio. Obviously, we're really excited. We know a lot of investors are excited about LP and so need to make sure we're fully capitalized there. And then the other big piece is just when we think about these competitive landscapes, us being a smaller company, really want to maybe over-index on an indication that I know for a fact we can take all the way, just because it's lower capital intensity, trials are a little smaller. So, you know, that's why you're seeing that move there. And, of course, we got very valuable information, you knows, over the last couple of months on tesopelumab's data in that, which, you know, gives us a lot of confidence. So that's really the reason there on that front. And then your other question, I just blanked on, oh, EOE design. So their seamless design is more about not losing time in study startups. So the Phase 2B, you don't really need any approvals to do that. The Phase 2b is the dose-ranging portion, and, you know, we'll roll through basically a 16-week kind of dose- ranging portion of that, and then we'll, you know, go straight in. It'll all be part of one protocol, and should the results come out how we would hope and expect, then we would just roll into the Phase 3 portion. Thank you. I'm sure no further questions. So with that, I'll hand the call back over to CEO Neil Walker for any closing remarks. Thank you everybody for joining on this call. Obviously, it was lengthy, a lot to cover. Very excited about the data and what comes next and certainly excited about embarking on the next stage with the bispecific and EOE and also reporting out on LP study start in the coming weeks and then getting into the data next year. Appreciate it. Ladies and gentlemen, thank you for participating. This does conclude today's program and you may now disconnect.