Aclaris Therapeutics Inc ATI-052 Interim Phase 1a Clinical Trial Results Call Transcript

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

Question: Biren Amin - Piper Sandler - Analyst : Maybe I could start off with -- on the PD data across both IL-4 and TSLP stimulated CCL17 assays, it seemed like the TSLP inhibition was a little bit more pronounced. In your view, what was driving that? I mean you clearly saw IL-4 inhibition as well, but it seemed like TSLP inhibition was slightly better? LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies.

Question: Biren Amin - Piper Sandler - Analyst : Got it. And then maybe just a follow-up. I think you mentioned that the Phase II AD trial would potentially evaluate every 12-month dosing. But I wanted to ask on the Phase Ib, if you could tell us a little bit about the dose selection and the frequency of dose administration in both the Phase Ib trial for atopic dermatitis as well as for asthma and the endpoints that you're hoping to evaluate and I guess, the time course as well for both of those studies. Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder Yes. Just to clarify, we're anticipating up to 3 months, not 12 dosing. But Jesse, do you want to just comment on the Phase Ib study designs?

Question: Biren Amin - Piper Sandler - Analyst : That's perfect.

Question: Raghuram Selvaraju - H.C. Wainwright & Co - Analyst : Congratulations on this data. I was wondering if you could comment on specifically the plan to explore 052 in asthma and how this fits into the overall clinical prioritization of indications for this asset, particularly in the context of what you previously had indicated regarding preference for dermatological indications versus indications within respiratory disease. And also, if you could comment on what you see as potential advantages in either the asthma or atopic dermatitis indications from a competitive landscape and competitive positioning perspective. Also wanted to see if you could provide us with some additional color on what you anticipate to be the commercial implications of a once every three-month dosing schedule, which was indicated in the press release as being a possibility for 052. Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder Yes. Thanks, Ram. So yes, clearly, we're interested actually in both dermatology and respiratory indications. And that's why we have 2 Ibs that will be kicking off very shortly here in both atopic dermatitis and asthma. And we think that the opportunity to expand into virtually all the similar indications that dupi is currently either approved in or being studied in is quite likely. I mean that's the big vision. And I think given the data that we showed here where we're getting complete inhibition at very low doses, this way exceeded our expectation, particularly for a healthy volunteer study. So I'm really excited about the potential in both derm and respiratory. And I think atopic dermatitis is a very fast-growing market. We still have not maxed out the efficacy in that indication. And so I think it's a great time, particularly with those of us who have bispecifics. And now we're -- we show that the art of the possible there with an IL-4R TSLP. So we think that from a competitive positioning standpoint, we're well positioned to show potentially best-in-class efficacy, just extrapolating all the data we have from our TSLP MAD, all the in vitro data and then the data we just presented here today. And then on the respiratory front, I think there's similar opportunity. Obviously, we're still hitting efficacy ceilings. That's why everybody is so interested in hitting multiple targets now. And I think the dosing interval, it's interesting. If you're talking about dosing intervals that involve Q2-week administration that then go to Q3 month or longer, I think that's a meaningful jump. I don't necessarily think that going from two to three months really matters or one to three months really matters all that much when -- if you're driving superior efficacy, right? So we do think we can get out to three months based on all the data we showed. But if it was two or three, so long as we're showing, again, complete inhibition of chemokines like TAR and we will be continuing our work on this study, generating additional biomarker data. So we're really excited about it. I mean I think if you go back and you look at this and just from a practical perspective and show the progression from 30 to 120 to 360, just beautiful dose response and not just complete inhibition, but sustained. Imagine what we're going to be showing with the MAD dosing.

Question: Charles Ndiaye - Stifel, Nicolaus & Company Inc - Analyst : This is Charles on for Alex. Congrats on the initial data. I think maybe a couple of questions from my side. Maybe first, is there anything you can say on the MAD portion that you're observing so far, either from a safety or PK/PD perspective? Does it seem consistent with what you've seen from the SAD side? And then I guess on AEs, I understand these are mostly ISRs, but anything else that was notable would be great. Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder Thanks, Charles. Yes. No, there was really nothing else notable. It was very clean. Of course, like everybody else, we look for things like conjunctivitis, infections, things like that. And so far, so good. We haven't seen anything related to that. And the ISR profile is actually quite limited and quite mild and even through the MAD portion. And you'll see that in the slides that we aren't seeing anything different in the MAD. In fact, it's just the curves are getting better. You can see that in the PK profile. We're out to 480 now, and we're going to continue to follow that data out through day 143 or so. But yes, still -- that's why we're so excited about the SAD data because, again, just showing the PK and PD in particular, up through 360 and you're seeing the numbers that you're seeing with complete inhibition. And usually, the general rule is with these biologics that as you go up in dose, it's pretty predictable. And so we expect to see even better at 720 on the SAD and then even better on the 240 MAD and 480 MAD.

Question: Prakhar Agrawal - Cantor Fitzgerald LP - Analyst : Congratulations on this update. Maybe just quickly on the injection reactions. I know it is only injection redness, but maybe if you can talk about the ISRs in general, what you're seeing? And then on the Phase I atopic dermatitis trial, maybe if you can remind us about the rationale for testing weekly doses in the Phase I, given the long half-life you are seeing with the bispecific? Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder Okay. I'll hand the Phase Ib to Jesse, but the ISRs, we really just didn't see much. The majority of it was mild, just self-resolving. If you look at across the cohorts, there wasn't any sort of increased incidence as dose went up. In fact, when you look at the 480 MAD, 2 placebo patients had some mild redness. So it was really unremarkable. So -- which I was really happy to see because as we all know that, that can be problematic down the road and I think gives us a lot of confidence in the program moving forward. And on the Ib, my initial comment would be like we're trying to show in a proof-of-concept study in AD in a very short study, kind of a max effect to help inform decisions as we move to the Phase II. And so that's why we're going to dose aggressively there. And Jesse, do you want to maybe comment as well?

Question: Pujan Patel, M.D. - Leerink Partners LLC - Analyst : This is Pujan Patel on for Tom Smith. So a couple from our end. With the encouraging Phase Ia data so far that we saw with 52 on hand, how do you guys plan to prioritize internal resources between both and 52 programs moving forward? And then regarding the Phase Ib proof-of-concept design for AD, can you provide a little more detail about your patient enrollment strategy? Is there like a target mix between biologic naive and biologic experienced patients that you have in mind? Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder Yes. Thanks for those questions. Could you repeat the first one, please? LSEG STREETEVENTS | www.lseg.com | Contact Us consent of LSEG. 'LSEG' and the LSEG logo are registered trademarks of LSEG and its affiliated companies.

Question: Pujan Patel, M.D. - Leerink Partners LLC - Analyst : Yes, sure. So with the encouraging data that we saw today, how do you plan to prioritize the internal resource like between both end, 2? Could we potentially see like a strategic shift in capital R&D focus? Or is that something we'll see more so after the Ib? Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder Yes. No, it's a good question. And so we think both have places in the market. Clearly, the AD study is going to read out in the second half of this year. We're excited about that. I think this bispecific data just provides further evidence of the potency of our compounds. And so we do think that a tezepelumab has a place in the treatment armamentarium of dermatologists who want a nice background therapy. We know there's polypharmacy out there with AD. And we already had kind of messaged earlier in the year that we won't be allocating our own capital against respiratory indications there. We'd be looking at partnerships. I think given the bispecific data that we have now, obviously, we're going to be prioritizing this a lot more. And that's why we messaged today about getting into a Phase IIb in AD at a minimum. So I think that's where you'll see us putting our dollars. We're really excited about the bispecific. We think we've shown quite a compelling profile so far. And in all likelihood, we'll partner the tezepelumab. And I would say that folks talk about combo treatments a lot, and we definitely have a best-in-class potential on our tezepelumab with our residents' time and think that, that would be a unique opportunity to combine with a variety of other constructs. On the -- what was the second question because I was having trouble hearing you.

Question: Pujan Patel, M.D. - Leerink Partners LLC - Analyst : Yes, apologies for that. Yes. So the second question, for your -- the Phase Ib proof of concept in AD, can you provide more detail like on your patient enrollment strategy? Like is there going to be a target mix between biologic naive and biologic experience specifically dupi, obviously? Or anything on that would be great. Neal Walker - Aclaris Therapeutics Inc - Non-Executive Chairman of the Board, Chief Executive Officer, Co-Founder Jesse, do you want to comment on that?