Aclaris Therapeutics Study result

Thanks, Andrew. Good morning, everyone, and welcome to the Aclaris Therapeutics conference call to review the positive primary analysis results from our ATI-052 phase I-B 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 investors section of our corporate website, aclaristx.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. 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 risks and uncertainties that could cause actual results to differ materially from those expressed in or implied by these statements. For more information on such risks and uncertainties, 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, Neal 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 Balthaser, our Chief Financial Officer, will also be available for questions following the prepared comments. With that, I'll turn the call over to Neal.

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 TSLP 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, ATI-052 targets type 2 inflammation at two important points in the pathway.

TSLP 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 TSLP upstream and IL-4 and IL-13 signaling downstream through the shared IL-4R receptor. The binding interface is multiparatopic, designed to deliver best-in-class potency and long target retention. A YTE mutation extends half-life, supporting less frequent 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-4R as a mechanism is approved across 5 indications, and because it blocks both IL-4 and IL-13, it covers the biology that drives asthma and other Th2 diseases. By contrast, IL-13 selective antibodies are thus far 0 for 8 in late-stage asthma and eosinophilic esophagitis programs, so blocking IL-13 alone hasn't been enough to match dupilumab, which is an IL-4R blocker. TSLP adds complementary validation in EoE, asthma, and CRSwNP, 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 in atopic dermatitis is described on slide 6.

When looking at atopic dermatitis data, not all patient populations are equal. There are two ways to look at severity, EASI over 21 and IGA IV status. IGA IV is more reliable in dictating severity by largely taking extent out of the equation. Patients who begin with more severe disease, like an IGA IV, for a variety of reasons, have further to go to reach the same clinical endpoint than more moderate patients like IGA III. One can clearly see that the dupilumab and lebrikizumab data illustrate this well with stark differences between IGA III and IGA IV 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.

Starting 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 5 weekly loading doses ending at week 4, we saw meaningful placebo-adjusted reductions from baseline in EASI and PP NRS. 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.

In the skin, we saw 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 Guttman's lab at Mount Sinai only increase our confidence in ATI-052, the role of TSLP in the underlying biologic rationale. 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 ATI-052. The results demonstrated that these patients improved broadly and rapidly as measured by FeNO and FEV1, with maximum improvement occurring in only 2 weeks. 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, and his experience with ATI-052 as an investigator in this trial. Jesse will then return to discuss the results in asthma. Finally, I'll be back at the end to conclude the call. I'll turn the call over to Jesse.

Jesse? Thanks, Neal. Good morning, everyone.

I share Neal's excitement about these strong results in both trials. As Neal said, ATI-052 achieved proof of concept in AD, with robust improvements in the extent and severity of disease, as well as in itch in a broad and diverse population. This study evaluated a load-in dose format of 5 weekly doses of 480 milligrams of ATI-052 or matched placebo over a 29-day interval. We enrolled 14 AD patients, randomized approximately 3 to 1, and we followed them through day 57 or week 8. The data we're presenting today reflect everything available once all patients completed their week 8 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 4. As Neal mentioned, we targeted a severe population, requiring a baseline EASI 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 EASI and PP NRS. 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% were IGA IV. 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 EASI in patients with darker pigmented skin. Late-stage AD studies typically enroll 35%-40% IGA IV patients and a higher proportion of White patients than we did here. 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 EASI from baseline. The other did not meet eligibility criteria.