Good morning, everyone. My name is Lucy Lai, a Research Associate at H.C. Wainwright. It's a great pleasure to welcome you all to H.C. Wainwright's 27th Annual Global Investment Conference. Thank you for taking the time to join us today. We hope you'll find the sessions insightful and engaging. Now, I'm delighted to introduce our next speaker, Dr. Neal Walker, CEO of Aclaris Therapeutics, a clinical-stage biopharmaceutical company focused on developing novel drugs for immuno-inflammatory conditions. Walker, please. Thank you, and thank you for having us here today. I'm Dr. Neal Walker. I'm the CEO and Chair of Aclaris Therapeutics. Aclaris is a development stage biopharmaceutical company focused on both small and large molecule discovery and development. What underpins our company is actually our proprietary kinase small molecule discovery engine. Now we've added a large molecule discovery engine. We've complemented that with an in-house multidisciplinary team that all come from large pharma: ex-J&J and ex-Pfizer. It really gives us large company capability within a small company. We have three clinical stage assets there on the left with a robust preclinical portfolio. We have a very strong balance sheet, $181 million, that takes us all the way through into or past the second half of 2028. This is our pipeline. ATI-045 (Bosacitab) is a TSLP monoclonal antibody. This is in Phase 2. It's actively enrolling in an atopic dermatitis study, and that enrollment is going quite well so far. Our second Phase 2 asset is ATI-2138, and this is an ITK/JAK3 covalent inhibitor. It's orally administered. We recently reported out positive 2A data in July, and we're excited about moving into the second indication later on at the end of the year. The third clinical stage asset is ATI-052, and this is a TSLP/IL4R bispecific construct based on the same TSLP best-in-class monoclonal antibody as ATI-045 (Bosacitab). This is currently enrolling SAD-MAD work, and we'll report out data towards the end of the year, early next. We have, like I mentioned before, a robust discovery portfolio highlighted by one of the assets that I'm most excited about, which is an ITK-selective inhibitor, which is orally administered, and it goes after Th2 diseases, a lot of the Th2 diseases that are the domain currently of biologics. With this broad portfolio, we're tackling a lot of very large and unsatisfied immuno-inflammatory markets. There's still a tremendous amount of unmet need, particularly in atopic dermatitis and various respiratory disorders. I think we're pretty uniquely positioned in that because we have oral small molecule and large molecule therapeutics, we can address a broader array of the target addressable market. These days, with all the competitive intensity, I think that's important to note. First, we're going to go over our first Phase 2 asset, which is ATI-2138. ATI-2138 is an oral small molecule covalent inhibitor of ITK and JAK3. It interrupts the T-cell receptor signal by inhibiting both ITK and JAK3. It's highly potent for both ITK and JAK3, sub-nanomolar potency, and it really has unique dual pharmacology. We say best-in-class potential because there's two other compounds out there that we'll talk about in a second that leverage a little bit of this technology. Corvus has an ITK-selective, and Pfizer has ritlecitinib, which is approved in alopecia areata. We have completed SAD-MAD work, allowing dosing of ATI-2138 up to 40 milligrams b.i.d., and it's quite well tolerated. This is a comparison and just kind of highlighting the unique dual pharmacology of ATI-2138 versus ritlecitinib, again, which is Pfizer's approved drug in alopecia areata. If you look on the right-hand part of the slide, this is a JAK3 assay looking at IL2-stimulated interferon gamma release. We can see a 5x difference in potency on that side of the molecule. If we look on the left-hand side, looking at an ITK assay, we're 44x more potent than ritlecitinib. In fact, ritlecitinib just kind of tickles ITK at their currently approved dose. Of course, we also, and this is all done in-house in our labs, we also compare ATI-2138 to CPI-818, which is Corvus's ITK-selective. If we look at the ITK biochemical enzyme potency, ATI-2138 is 15 to 38 times more potent than CPI-818 in inhibiting ITK enzyme activity. If we turn to the right-hand part of the slide, ATI-2138 is significantly more potent than CPI-818 in blocking the Th2-derived cytokines, IL4, IL5, and IL13. It's basically a hundredfold. It's quite remarkable, actually. In addition to all of this work, we've conducted an extensive amount of preclinical work further characterizing ATI-2138's activity in tried and true preclinical models like the mouse T-cell transfer model for IBD, various RA models, and also recently a vitiligo mouse T-cell transfer model. The take-home point here is that if you look across the board, both on the left and on the right, we do use positive controls, and we're superior to both of those in terms of the anti-inflammatory activity in these preclinical models. The next step was to actually prove out this potency advantage in the clinic. Last year, we embarked on a Phase 2A open-label study in atopic dermatitis. We chose atopic dermatitis because we only had tox coverage up through 12 weeks. Otherwise, we would have jumped right into alopecia areata, but we needed six months tox coverage. This was a 12-week study. We took a pretty low dose at 10 milligrams b.i.d. and enrolled 14 patients. These patients had moderate to severe atopic dermatitis. We looked at three different things, obviously safety, efficacy, but most importantly, from my perspective, we looked at pharmacodynamics. One, we wanted to prove out the unique pharmacology of ATI-2138 and show the value there. In addition, we wanted to kind of pave the way to show why we're so excited about the ITK-selective that's coming into view into an IND in 2026. A little bit on the results, favorable tolerability profile, go into that in a second. Definitely showed clinically meaningful improvements in line with what JAK inhibitors would show in AD. Probably, again, most exciting to me was the PD results were just fantastic and really validated ITK as a therapeutic target. On the safety side, there were no severe adverse events, no treatment emergent adverse events, no discontinuations due to adverse events, all mild and self-limited except for one case of myalgia that was moderate. No safety signals on the labs or any of the other parameters measured. This is some of the efficacy data. If we look at mean change from baseline EASI and also median, because we have a small N, we looked at means and median, and I'll talk about that in a second in the next slide. Nice results, 70% change in mean at week four, carried out through week eight, a little bit of a decrement at week 12, which I'll show you why that was in the next slide. On a median basis, of course, it only gets better. This is a spaghetti plot. We felt it was important to include this. We had 10 patients in the per protocol analysis. Nine out of the 10 patients were consistent, did great. One patient, however, was a little odd in that this patient kept getting worse throughout the study. There were some compliance issues with this patient. She was 19 years old, not sure she was taking the medicine as prescribed. Interestingly, when we had this patient's PD assessment done by an independent lab, they independently identified her as a statistical molecular outlier by over four standard deviations. What that means in plain English is that the inflammatory pattern was so vibrant that it was very inconsistent with atopic dermatitis. We think in addition to atopic dermatitis, she had something else going on. Just a little bit of explanation around a small N. Of course, we put together an analysis of what it looked like when you exclude this outlier. No surprise, numbers get better both on a mean and median basis. This was an interesting result, 63% improvement on itch score. This is important because this is really how patients feel, you know, when they're on these drugs. One of the first things that they notice is less itching. This was quite rapid. I think at week four, it was around 44%, which as you can see, would fall in the middle of the order here, even at four weeks. This was the assessment at 12 weeks. Some of these drugs looked at 16 weeks, but just a best-in-class result on the itch front, which we really think is being driven predominantly by the ITK side of the house, given its biology. The next layer here was looking at all the PD effects. Again, we're trying to accomplish two things in a pretty small study. One is validate the unique pharmacology with ATI-2138 and also paint the picture for ITK next gen, which is coming next year. We did a bunch of work in-house in St. Louis in our labs there. We looked at ITK and JAK3 assays and also target occupancy and did some immunophenotyping. Then we layered on with the help of Emma Gutman's lab, who's a renowned dermatologist out of Mount Sinai. We did punch biopsy analysis on five patients who consented to that. We did tape strip analysis looking at RNA-seq, obviously over 16,000 genes, and then a variety of biomarkers in the plasma via O-link. What we found here was, this was actually the thing that made me most excited about this data, just a clear demonstration of modulation of both the ITK and JAK3 pathways. Sometimes it's difficult to tease that all out 100%, but we went a long way to validating the ITK path. We saw near complete and sustained inhibition and occupancy of ITK. We looked at proteome and transcriptome lesional skin tape strip analyses, measured importantly at trough to better represent steady state, and showed ATI-2138 dependent reduction of multiple inflammatory pathways associated with ITK. You can see that list there looking at the strong down regulation at week eight and week 12. A lot of those PD biomarkers will look familiar. CCL17 is an example, IL-13, et cetera. I think one of the most interesting things that we have to do a little bit more work on and further defining is we saw really robust action on the fibrosis-related markers and very strongly down-regulated by ATI-2138 across the board. That could be due to the robust impact on inflammation, but I think we have to tease that out because that could augur well for potential different indications. In terms of next steps, we said this from the day we started this study that atopic dermatitis was kind of a signal-finding indication. We like to reserve atopic dermatitis for ITK-selective, which is going to have, when you engineer out the JAK3, a much better target product profile for that indication as an oral. There is a wealth of indications we could pursue with this mechanism. We're currently exploring alopecia areata, which we would anticipate starting in the beginning of next year. Now moving on to our second Phase 2 asset, ATI-045 (Bosacitab). Bosacitab is a humanized monoclonal antibody targeting TSLP. I think we're all pretty familiar with TSLP. It's pleiotropic. It has broad activity, broader than most people think. It's an alarmin and it's a master regulator of type 2 immune responses. It's involved in both actually the induction phase and effector phase, as well as, believe it or not, non-Th2 processes. What I liked about this asset, it's proven biology. We know it's safe, you know, and we know a lot about this space vis-à-vis Tezspire. It's the first approved TSLP in severe asthma. One of the things we did before we in-licensed this asset from our colleagues at BioSheng in China was we wanted to understand, obviously, it's a competitive area. We wanted to understand how Bosacitab stacked up against both Tezspire, but also more importantly, how it stacked up against the relevant competitive landscape. We have this ability to do all this testing in-house. We have all this expertise. We put together an MTA, worked for six months before we did the deal, and did about six different assays, repeated the work three times, and then repeated it at an outside vendor. What we found was that Bosacitab was 60 times more potent than Tezspire, which is great, you know, but still not enough. We also found that it had quite unique binding characteristics. It binds in a biparatopic kind of construct. We also took it a step further to understand that and found that it had an exceedingly long residence time, which I'll go into in a minute. This is what I was talking about before. We tested it against several different development stage TSLPs and showed once again best-in-class potency, in some cases by a long shot here. This made us feel pretty good that going into this, we had a solid molecule versus those we knew were out in the competitive space. One of the things we really wanted to understand and tease out, because when you look at SPR, it has a lower limit that you can't really ascertain, like the order of magnitude versus other compounds. Our scientists identified TRFRET as an interesting assay to look at residence time. What this basically means is our antibody binds to TSLP and it's sticky. It sticks to the alarm and if you think about it logically, I'd much rather have something that sticks to the alarm and doesn't allow that to cycle off and then hit the receptor again. That kind of doesn't make a lot of sense. To our great surprise, we found that our monoclonal antibody had 400 hours of residence time. You can see nobody else is even close. The next closest is in the 20s. We were able to test the TSLP receptor compound as well. We're pretty excited about that. It's 20 to 100 times longer than the comparator antibodies. I think this solidifies our best-in-class potential claims. The next step, all this in vitro preclinical data is great, but how does this translate into the clinic? This was a study that was conducted by BioSheng that read out in September prior to us doing the in-licensing deal. This was a U.S.-based study done at seven U.S. dermatology sites. We dosed, or they dosed, every two weeks. We actually think we can dose every eight to perhaps 12 weeks, but the dosing was done every two weeks to make sure we maxed out the effect. Looked at all the traditional atopic dermatitis endpoint safety, of course, enrolled 22 subjects, and then looked at the primary around week 24 or week 26. You can see here, just looking at the, this is a plot of exposure versus efficacy and pretty rapid effect. If you just pay attention to the purple line, getting effect is as early as four weeks. It's notable that you're not getting peak effect until later on in the game, kind of similar to what you might see with the OX40 ligand compounds. It doesn't actually peak in this graph until week 28, and that's after the last dose. I think it's interesting if you look at this from an EZ75 perspective, we're getting about eight weeks, and if you squint a little bit, 12 weeks of EZ75 sustained response. That makes me think that we've got more dosing interval to play with here. Our China partner is actually dosing in the respiratory studies currently Q4 weeks. This is just another way to look at the data. Again, this is open label, so you have to provide a little bit of a discount factor to some of this. Obviously, there's a little bias. If you look at the EZ75 and IGA numbers, they're just wonderful numbers, 94%, 88%. Even if we're getting a partial of that in a double-blind, placebo-controlled study, that would be class leading. We're pretty excited about this molecule. This is just another way to look at the data, just comping versus dupy and looking at some combos with topical corticosteroids and Tezspire with topical corticosteroids. Same rapidity of response, but a much deeper, more durable response. This is important. I trained as a dermatologist. When you're looking at these patients, this is a treat the flare disease, making it different than psoriasis. You want a smoothing out of the flares over time. What patients don't want is the peaks and valleys. If you can give a very safe drug like a TSLP as kind of background therapy, think methotrexate in RA, that could be applicable to not only moderate to severe, but also mild patients and just giving a more sustained response over time. The next step after conducting an open-label study is to jump into double-blind, placebo-controlled. That's what we did. We are currently enrolling. It's going quite well. This study is due to read out in the second half of 2026. Looking at all the traditional endpoints and 90 patients, two-to-one randomization, moderate to severe population. It's important to note that we're addressing the rising placebo response in this condition with screening and pictures. We're doing that with two dermatologists to make sure we get the right patients in. Next steps are to complete the study, read out in the second half of 2026. It's also notable we have three respiratory studies ongoing with our China partner in China. They have two Phase 3 studies, one in CRS, one in severe asthma that are ongoing, and a Phase 2 study in COPD. Next is the bispecific. This is a bispecific using the same antibody as ATI-045 combined with IL4R. This is also Fc engineered, potentially extending the half-life. This molecule has retained the same dissociation kinetics and residence time as the TSLP monoclonal antibody that I just reviewed. We also tested this versus both Tezspire and dupilumab combined, and we showed a 4x increase in terms of potency in a CCL17 release assay. The next step with this was to jump into SAD-MAD work. This will complete in the December timeframe, probably read out top line in January. We'll roll into two 1B studies, one in respiratory, one in dermatology, with the hope of increasing that efficacy ceiling. I've alluded to this a number of times throughout the presentation. Very excited about our oral small molecule selective ITK inhibitors as our next-gen ITK inhibitor. The goal here is to engineer out the JAK. As we all know, whether you like it or not, there's always a specter of getting a black box with the theoretical risks around JAKs. When you're going into a condition like atopic dermatitis, you'd like to engineer that out and create a better target product profile. We're moving two programs forward. One is very selective for ITK. The other touches both ITK and TXK, and that allows you to address not only the Th2 side of the house, but the Th1 side of the house. We think that's important. We're going to move both forward, and we're getting into IND in 2026. We'll be initiating SAD-MAD work there. I think we have a great team of ex-large pharma folks that have a rich set of experiences in both large molecule and small molecule. We have this wonderful discovery platform that allows us to quickly not only analyze other people's compounds, but also invent our own and respond to the dynamics in the market. Over $181 million on the balance sheet. We get cash runway through the mid-part of 2028. Importantly, execute on all the catalysts I just mentioned with about 15 to 18 months of cash runway post the last data readout. We feel pretty good about that position. In terms of catalyst calendar, 2026 is a big year. We've got catalysts coming on all four of our assets within 2026. We're excited to get into the new year. Thank you. Thank you so much for the presentation.