For. Hi everyone, and welcome to the H.C. Hi everyone, and welcome to the H.C. Wainwright Inflammation and Immunology Day. I'm Dr. Jade Montgomery, an Associate Research Analyst for H.C. Wainwright, and it's my pleasure today to welcome our speaker from Aclaris Therapeutics, CEO Dr. Neal Walker. Neal? Thank you, Jade, and thank you for having us here today. Good morning, everybody. My name is Dr. Neal Walker, and I'm the Chairman and CEO of Aclaris Therapeutics. Aclaris is a development stage biotech focused on developing potential best-in-class large and small molecule therapeutics. Underpinning our portfolio, we have world-class expertise in both large and small molecule drug development, as well as a proprietary drug discovery engine. Importantly, our team has both large and small company experience. Many ex-Pfizer as well as ex-J& J executives are on our team. Currently, we have three assets in clinical development, which include ATI-2138, which is an oral small molecule ITK JAK3 inhibitor with unique pharmacology; ATI-045, a uniquely potent monoclonal antibody targeting TSLP, a key alarm involved in numerous diseases; and ATI-052, a bispecific antibody targeting TSLP and IL-4R, which are two key components of TH2-mediated diseases. In addition, we have a preclinical portfolio highlighted by our next-gen ITK inhibitor, where we have engineered out the JAK3 component, as well as a few novel bispecific constructs that are in early-stage development. Our portfolio is complemented by a strong balance sheet with over $190 million in cash and runway through the first half of 2028, with additional visibility on incremental non-dilutive capital in the future. Our pipeline is broad and includes highly differentiated large and small molecule assets, all with multi-indication potential targeting multi-billion dollar target addressable markets. As I mentioned, we have three clinical stage assets. ATI-045 is in phase III clinical studies in China in severe asthma and CRS with NP, as well as a phase II clinical study in COPD. As a reminder, we are currently seeking ex-China partners for these indications. Regarding our internal programs, we recently initiated a global phase II study in atopic dermatitis with sites in the U.S., Canada, and Europe, and that study is ongoing. In addition, the IND for our bispecific TSLP IL-4R was recently allowed, and the phase I SAD/MAD work has begun. Finally, ATI-2138, our oral small molecule ITK JAK3 inhibitor, is currently in phase II. We recently completed this study, and we are awaiting final PD data, so top-line data will be reported imminently. Since the close of our transaction with Biogen in November of last year, we have been busy executing on our plan. We have hired a CMO, Jesse Hall. We have extended our cash runway by a quarter and a half and have continued to deliver on our clinical and preclinical plans. We have made good progress this year with a rich catalyst calendar expected in 2026. Our next update will be presenting top-line data from our 2138 POC study in AD, which, as I said before, is imminent. Post-reporting this top-line data, we look to initiate a clinical study in alopecia areata with 2138, report top-line data for ATI-052 SAD/MAD work at the turn of the year, followed by phase I B POC results in the second half of 2026. We will also report ATI-045 AD data in the second half of 2026 and deliver an IND with our next-gen ITK selective in the same year. Turning to ATI-045, or bosakitug, our potential best-in-class TSLP monoclonal antibody. Bosakitug is a humanized antibody targeting TSLP, which is a key alarm involved in pushing TH2 inflammation relevant to a number of skin, GI, and respiratory diseases. TSLP is a pleiotropic mediator with broad activity acting on a wide array of adaptive, innate, and structural cells. In addition to working on TH2 inflammatory pathways, it is also involved in a few non-TH2 processes. The expression of TSLP is elevated in both respiratory and skin diseases, and therefore this represents a great target to inhibit either alone as a monoclonal antibody or in a bispecific construct, and we have both. Tezepelumab is obviously approved in severe asthma and has been studied in a number of indications to date. How is our molecule different? As a reminder, prior to consummating our transaction with Biogen last year, we tested bosakitug in numerous assays, comparing it not only to tezepelumab, but also a number of clinical development candidates head-to-head. In all cases, we demonstrated enhanced potency with bosakitug. Here we show bosakitug versus tezepelumab demonstrating a greater than 60x inhibition of CCL17 production by human PBMCs. We believe this high potency is due to the very unique binding characteristics to TSLP. Bosakitug has an extremely low dissociation rate from TSLP, leading to long residence time and enhanced neutralization activity, which we then quantified. To quantify the residence time, we utilize the TR-FRET assay, where we are measuring dissociation time of TSLP from bosakitug in various competitor molecules. As you can see, we have an extremely long residence time of over 400 hours, in contrast to tezepelumab at 14 hours and others at 20 hours or less. This means we bind and stay bound, which we believe is very likely important in an alarm-based mechanism of action. You want to make sure that once the antibody binds to the alarmin, it does not quickly cycle off and remain free to bind to a receptor, which then perpetuates inflammation. Why is this high affinity and long residence time important? Here we show that the potency in a functional assay measuring CCL17 production from human PBMCs is quite robust versus the comparator molecules. We know in vitro that we are driving a more robust effect in functional assays. The next question that we had to answer was, how does this enhanced potency translate to clinical effect in patients? Prior to our license deal with Biogen, the company conducted a 22-patient single-arm study to answer that question. A phase II A POC study was initiated in the U.S. with bosakitug in patients with moderate to severe AD. Bosakitug was dosed over 24 weeks with a 12-week follow-up. In this study, we demonstrated a strong clinical response as measured by mean change from baseline and EZ score, which actually continued to peak through week 28 after dosing was complete at week 24. In fact, EZ75 response was maintained after the last dose for several weeks, supporting the potential for longer dosing intervals. The effect was rapid and sustained, showing the clinical translation of the potency that I've already covered. Equally as impressive was the responder analysis. Strong responder rates were observed for EZ75, EZ90, EZ100, and IGA. Although this was a single-arm study with all the caveats that that entails, rates of 94% on EZ75 and 88% on IGA response are very high in moderate to severe AD patients, which we believe further validates the enhanced potency of bosakitug relative to the competitive landscape. In this graph, we are comparing our results to those of dupilumab and tezepelumab. It is notable that the response is rapid and similar to dupi, but in contrast, bosakitug drives a deeper and more durable response over time when looking at mean change from baseline and EZ scores. On the heels of this impressive phase II A data, we have initiated a global phase II study in atopic dermatitis. We will be enrolling approximately 90 patients with moderate to severe AD with a two-to-one randomization. Treatment will continue through week 22 with a 10-week follow-up period. The primary endpoint is mean change from baseline and EZ score. One key component of our study is the incorporation of a rigorous picture review process prior to enrolling patients. This will be conducted by an independent central reviewer and then sent to the company to review prior to enrollment. In this way, we hope to mitigate against the growing placebo responses seen in recent years in some studies. As I mentioned, next steps, we have initiated this first study in atopic dermatitis with bosakitug, first placebo-controlled study, and we'll look to report the top-line data in the second half of 2026. As a reminder, we are also actively seeking partners to develop bosakitug in respiratory indications ex-China. Now moving on to our bispecific ATI-052, which is our anti-TSLP IL-4R bispecific, utilizing the same antibody binding regions of ATI-045 combined with IL-4R, which inhibits TSLP upstream and clearly immune cells downstream of the TH2 cascade, which we believe is likely important for enhanced activity in atopic dermatitis, severe asthma, and COPD relative to targeting a single inflammatory mediator. In this construct, we continue to leverage the best-in-class potential of our TSLP monoclonal antibody in terms of dissociation kinetics, residence time, and potency. This molecule is also half-life extended and has the potential to show superior activity than the single-target approach in a variety of diseases, as I already mentioned. As we see here, 052 demonstrates far greater potency, up to 4x versus tezepelumab and dupilumab combined in this functional assay looking at CCL17 release. On the heels of this, we recently announced the initiation of a phase I program with our bispecific, where we will look at safety, tolerability, PK, and immunogenicity of ATI-052. After completing the MAD portion of the study, which we'll complete at the end of this year, we will move into a phase I B POC in a yet-to-be-disclosed respiratory as well as a dermatology indication. We will be doing two phase I B proof-of-concept studies post the MAD work. As we have previously announced, the IND was recently cleared for 052 in April of this year. We have initiated activities in the phase I SAD/MAD program, and we expect top-line results from the phase I B portion in the second half of 2026. Now moving to our small molecule programs. ATI-2138 is an oral small molecule covalent inhibitor of ITK and JAK3. It is highly potent on both targets and can be thought of in the same class as ritlecitinib, which is Pfizer's approved drug for alopecia areata. Although our pharmacology is quite unique and distinct from ritlecitinib, which tends to more broadly inhibit members of the TEC kinase family. As we can see here, we compare quite favorably to ritlecitinib in terms of potency in the JAK3 assay, about a 5x increase on the right-hand side in potency and over 40x on the left-hand side, more potent in the ITK assay, which gives us confidence when thinking about indications like alopecia areata, vitiligo, or atopic dermatitis. Next, we show a potency comparison to CPI 818, where across all measures of ITK enzyme activity, we're showing that 2138 is between 15x and 30x more potent at inhibiting ITK, and that is shown on the left. In addition, 2138 is also significantly more potent at blocking TH2-derived cytokines like IL-4, IL-5, and IL-13. This positions us as the most potent and potential best-in-class molecule in targeting ITK. Last year, we embarked on a POC study with 2138 in patients with moderate to severe atopic dermatitis. The study was 12 weeks in duration with the primary endpoint of safety and secondary endpoints of PK, PD, and efficacy. Our main objective with this study was to demonstrate the unique pharmacology and safety profile of 2138 relevant to indications such as atopic dermatitis and alopecia areata, demonstrate the importance of ITK through the PD analyses, which has been extensive, and bridge this data importantly to our next-gen ITK selective molecule. The study enrolled 14 patients with moderate to severe atopic dermatitis. It is in fact complete, and the data will be available imminently once we receive the full set of PD data from our external partner. In terms of next steps, we look to report out top-line data on our phase II A open-label study of ATI-2138. We'll be focusing on the safety and efficacy, and again, importantly, the PD as it relates to both 2138 and guidance related to the ITK selective. Next indication for us with 2138 will be alopecia areata. We think that's a better fit than atopic dermatitis for this particular molecule given the JAK effect that we have. Now moving to our next-gen ITK selective. ITK is important in driving both TH2 and TH17 inflammation. Blockade of ITK inhibits key cytokines like IL-4 and IL-13 involved in allergic and atopic diseases. We plan to file an IND on our next-gen ITK molecule in 2026 and begin phase I work. In summary, we have a highly accomplished executive team with world-class small and large molecule capability. We have a strong balance sheet with over $190 million, which gives us a cash runway through mid-year 2028. We have a balanced portfolio of three clinical stage assets and a new IND coming into focus in 2026, along with multiple clinical catalysts in 2025 and 2026. Thank you for your attention.