Aclaris Therapeutics Inc R&D Day Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Prakhar Agrawal - Cantor Fitzgerald - Analyst : Hi, Prakhar Agarwal from Cantor, thanks for hosting this session, really informative. Maybe for the by specific, you mentioned that the sad portion is completed and the MAD is ongoing, so maybe just talk about the initial expectations on the immunogenicity profile and the half-life for this drug based on the data that you're seeing. And will the MAD follow-up next year be enough to de-is the immunogenicity profile for this drug, and A follow-up to that, you realize that it's just healthy volunteer, but will you be measuring any biomarkers related to asthma or atopic dermatitis that can, de-risk, as you move into the disease Patient? Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder Sure, thank you. I'll start and I'll hand it off to you. So, at least on the biomarker side, we are looking at that. I mean, it's healthy volunteer, so it's somewhat limited, but I think it gives you some least reasonable information directionally and as it relates to the other two questions, I'll pass that to you. Yeah. So, In terms of immunogenicity that you mentioned, so you know we don't have any readouts from the 1A yet in the healthy volunteers in PK or ADA, but what we do know is it's the same TSLP antibody as 045, and then that 2A trial and in healthy volunteers, we saw a very low ADA and so we're expecting that we're going to see a similar profile. I'll be surprised if we don't, but you never know. And so we're going to have to wait on that for, the first part of the year. But as Jesse mentioned, the oneA, the set has already finished dosing, and we've already initiated mat dosing, so that will be complete by the end of the year. Thanks. Unidentified Participant Thanks so much, Tom Smith Leering Partners. Thanks for putting together this really comprehensive event. Two questions if I could, I guess first on, Osaka tug and the photographic review that you've instituted in the phase two. Just wondering if you could comment on the experience you've had with this to date, any sort of visibility into the screen failure rates at the vendor or the company level, and, can you just elaborate on how you're able to track patient progress through the balance of the study there? And then on ATI-2138 in Lichen planus, I think there's been some phase two studies, one with an IL-17 inhibitor, one with a topical jack. You just talk about some of the results there and how you think IT/JAK3 could be more effective and, any learnings from the existing clinical experience that you plan to implement in your plan phase two. Thanks so much. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 14, 2025 / 1:00PM, ACRS.OQ - Aclaris Therapeutics Inc R&D Day Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder Sure, well I'll take, I'll start there and have the team fill in where necessary. So on the Central review, I do, I always kind of find it remarkable when folks talk about, well, I'm setting these bars of, E 16 and 10% body service area, and the reality is none of that matters if you can't lay your eyes on the patient and see what you really have. And unfortunately, as Doctor Cameron astutely pointed out, there's a lot of things within atopic dermatitis itself that can be confounding. But then think about just being very simplistic, a red scaly raft that can look like a lot of different things, and there are some sites that throw patients in that have fungus or psoriasis. And believe me, I've done this a number of times, you wouldn't believe what I see that that comes in, that comes into these studies. So I think it's, I know you guys always TRY to dissect and cross trial compare. And if you saw what I saw, you would kind of give that up because it's really difficult to do that when you're seeing some patients who don't even have AD, which is a lot, and then you're seeing patients that don't even have the extent of disease necessary even if I set an E 16. And Dr. Cameron also rightfully pointed out that there's a tremendous, and this is in the literature, this is nothing new. There's a tremendous amount. Of interrate or variability. So as you're seeing patients back, remember, it's a static assessment. You don't get to go back and say, well, let me check the last picture. So you're better off having a provider who saw that patient coming in. So at least they have a feel for extent when they're looking at the patient, as a, as a follow-up. So, I feel really good with what we've seen so far. And usually when you do this, when I've done this in the past, and you set the stage that you're going to be watching that, you go in thinking logically that the spleen failure rate's going to go through the roof, but, nobody likes extra work, right? So, if they know you're looking at this stuff, they're going to put in patients who make sense. And so we really haven't seen a big uptick. You see, you usually see that in the beginning of the study is everybody's getting a feel for what you want, because there's certain trials that you want a certain type of patient within that broader category of moderate to severe. So I think we started out with a little bit of a higher screen fail rate, but then it just modulated out and we're ahead of schedule on the enrollment side, and I can tell you this will not fail because we don't have the right patients and that is a guarantee and it is a lot of work, right? I mean, I, I'm sitting here doing that as a day job as well, but it's important, because we really want to understand that. Any, does that answer your question on that? Okay. On the LP front, so it's interesting that there have been some investigator initiated studies that have shown proof of concept. It's one of the things I liked about it there. I gotta be honest, I watched with great intrigue, the strategy Roy Vent employed with their, Jack T2. I think it's smart, we are operating in intensely competitive times. Renvo just reported out date in LP Shariata, so now we're going to have another player in that space, and so the decisions that we have to make are, we like all these indications, but what's the lead, because that's how, that helps set price, as we all know. And so, when I take a look at that landscape and TRY to decide. Do I lead with alopecia or do I go into something like a scarring alopecia, which kind of led us to lichen planus because lichen planopylaris is a very particular type of scarring alopecia where we've seen good efficacy there. Remember, we just presented data with our ITK/JAK3 that showed remarkable effects on fibrosis. So it's, and we also know that LPP like in planopylaris is orphans. So there there's a lot of different ways to go here. And we're not saying we're abandoning alopecia areata because we still really like that, but I think it's important what you go with as your lead, and so that, that's what we'll be continuing to assess going forward, but that, that's where we're leaning at the moment. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 14, 2025 / 1:00PM, ACRS.OQ - Aclaris Therapeutics Inc R&D Day

Question: Roger Song - Jefferies LLC - Analyst : Great, Roger on Jeffrey, thank you for putting together this presentation. Also question the rate to the 52, so looking at the pharmacology and the in vitro efficacy seems, on the 13R4 side maybe slightly lower than DP but comparable, but when you add on top of the TSLP, much higher than DP. So with this profile, how do you think of the position? In terms of the, biology wise, this will be better suited for DP9 experience and then in terms of indication selection because DP has a bunch of the indication which one may be better for this profile with the combination.

Question: Roger Song - Jefferies LLC - Analyst : Got it. Thank you. Very quick follow-up in terms of the half-life, looking at the current phase two design is for the everyone's, once weekly dosing. So is that because you want to test the efficacy part and then to maximize, max out the potential there and then what's the eventual maybe induction versus the maintenance dosing regimen for the 52 potential.

Question: Seamus Fernandez - Guggenheim Partners - Analyst : Seamus Fernandez Guggenheim, so a couple of quick questions, Neal, not a lot of questions on the ITK and the ITK selective approach, we're going to get some potentially some information from. The CPI-818 molecule, in the near term. What do you mean looking for in that data to really kind of, maybe assess proof of principle as it relates to the opportunity in atopic dermatitis for that asset and then beyond that, REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 14, 2025 / 1:00PM, ACRS.OQ - Aclaris Therapeutics Inc R&D Day when you just kind of think about ITK selectivity, obviously you've got this ability to dial in, dial out, but what is the real advantage of ITK selectivity. Especially from a safety perspective, as you look at this. Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder So, I think what we've seen out of CPI-818 is, at their highest dose level, the 200 BID, they showed a signal on a small number of patients. I think, you've seen what we've presented today, that that molecule is, quite modest, potency. And that does matter. And so I think the fact that with perhaps a molecule that that's not optimized that you're showing a signal that that should be encouraging and I know they have they have additional data coming up, but it's only a longer dosing interval. I'm pretty sure it's 400 GD and takes it out to eight weeks, so. What I'm hoping is that, again, kind of coming out of this meeting, we presented a lot of data on that side and what I hope is that people start recognizing, what we've presented, we have an exceedingly potent molecule, we got new ones coming down the pike in in 26. And, again, I couldn't be more excited about the ITK next gen approach and getting rid of the just theoretical jack risk because as we all know, Jack inhibitors are generating billions of dollars and everybody harps on the black box, but we did just see Renvo get moved up in the pecking order with, ulcerative colitis, and now to be used to had a DNF inhibitor, so. I think as time goes on, it's as predicted, at the end of the day you want to get a molecule that drives great efficacy and I know folks are fond of referencing, well, I can be a better oral doopy. I want to be a better oral jack, as it relates to the overall product profile, and I think the dialing in and out of TXK is important because as we talked about with the heterogen we know those are safe. Safe targets, but at least for what we know today. And by dialing that in and out, you're able to have a more robust effect across the patient population. We talk about this all the time with, people reference respiratory with low EOs, high EOs, and like, TSLP worked and kind of both do be more so on the high EO side. Well, what if you had a molecule that that does really well on the TH2 side but also pulls in that TH1 and can generate a more robust effect across a broader set of patients. That's what we're pegging off of and the fact that, as Joe presented today, we got a QD version, that that's a good setup for us.

Question: Parker - Cantor - Analyst : Hi, Praker from Cantor. Maybe a question for Joe on the ITK selectivity. You talked about the selectivity versus JAK3, but maybe it's just broader off target. Off-target effects, and what you saw in the kind of three. And second question, is there on the TSLP side, given that that you have much better potency and inhibition compared to teciliab, what are the safety implications of too much TSLP inhibition?

Question: Parker - Cantor - Analyst : Yeah, so in regard to the TSLPTSLP, so you know we have the 2A data, where we dosed, with 045, we dosed pretty high, right? 300 mg every two weeks with a 23 day half life, so there was a fair amount of accumulation as you saw also in the figure, and the safety profile was identical to Tezzy. Nothing popped out, it looked very safe. It looked like you'd be able to go down into the younger populations without any incident.

Question: Parker - Cantor - Analyst : Pipeline? Go ahead, Joe, I'll let you go first and I can close. Neal.