Good morning, everyone, and welcome back to day two of Oppenheimer's Annual Healthcare Conference. I'm Jeff Jones, one of the senior analysts on the team here, and I'm delighted to welcome multiple members from the Aclaris management team, to talk about the story. Why don't we start off with just a brief introduction to Aclaris, and then we can dive into your really exciting clinical stage pipeline?
Yeah. Thanks, Jeff. Yeah, Aclaris is a clinical-stage biotech company. We discover and develop both large and small therapeutics for the treatment of major unmet medical needs in the inflammatory and immunological space. Unique potentially to Aclaris is our leadership team is comprised of many individuals with extensive experience, both discovering and developing new innovative drugs and biologics. We've been in biotech and pharma companies like MedImmune and AZ, Centocor, J&J, GSK, and Pfizer. We've taken drugs literally from discovery through to the market. At Aclaris, we have three clinical-stage programs that are currently in or have completed clinical POC studies and through phase II, and another program that's expected to have an IND submission later this year. In 2026, our lead program, bosakitug, it's an anti-TSLP mAb, will complete a phase II study.
ATI-052, a bispecific comprised of the same TSLP, along with an anti-IL-4 component, will complete the phase I healthy volunteer portion of that study. We've recently presented some very compelling interim data from those patients, and complete top line results are expected later this quarter. There are two phase 1b studies, one in AD and the other in asthma, which we'll read out by the end of the year. On the small molecule side, we have ATI-2138. It's a very potent ITK inhibitor combined with JAK3 that will initiate a further clinical trial. IND is expected now for an ITK selective development candidate, which we just posted this morning, ATI-9494, and that'll also be submitted by the end of the year.
As you can see, 2026 is a very big year for Aclaris.
Absolutely. A lot to unpack there and a lot of really important catalysts for 2026. Maybe to start out with the most advanced, bosakitug, the anti-TSLP antibody. You've completed a phase 2a in AD already, and you're now in a larger phase II study in AD. Why don't you speak to the data you've shown to date in AD for the program, and, you know, really, given there's an approved TSLP antibody, how you think about differentiation here?
Yeah. bosakitug is an interesting molecule. We've shown what we believe to be best-in-class potential for this TSLP, and it's because it binds to TSLP with a 400-hour retention time. We've compared this to tezepelumab, for instance, that is about 20 hours or less, and even other molecules in clinical development that are even shorter retention time with those antibodies. When you have an alarmin like TSLP with very high potency, you really need to inhibit it hard and maintain that inhibition for a long period of time to allow that Th2 cascade to heal the skin to turn around. Ultimately, at the end of the day, this TSLP showed some really great data, as you pointed out, in phase 2a.
We had over 90% of EASI-75 response in a POC study. It was open label, so take it for what it's worth. In IJ01, we had over 80% responders. That was the impetus to move into a phase II study, and we're very excited to be able to read that out by the end of the year. We're excited for its potential.
Great. You know, as you mentioned, the 400-hour retention time, how are you thinking about dosing in the AD study, both in your phase II and I guess more longer term?
Yeah. That retention time really translated into also best-in-class potency, and it has a natural 23-day half-life. We believe, because of the phase 2a data, that we can dose every two to three months, because we showed an EASI-75 response after the last dose that extended through to three months. The reason why we took in the POC study, and again in the phase II, we took a two-week dosing schedule in, is because no one believes that TSLP is valid in AD as a target. When we're done this trial, if we don't show success and high response, then no one will ever have to investigate TSLP as a standalone therapy in AD again.
24 weeks of dosing, high exposure, long retention time, high potency, and we really focused on minimizing the impact on placebo response by making sure that we enrolled the right population. We used pictures for enrollment. We really feel like this study is sort of the Cadillac of investigating TSLP.
Got it. Just as a reminder, when you expect top-line data is second half of this year?
Yes.
With, you know, with the PK/PD, you talked about, you know, dosing every two to three months. Obviously, the benchmark in AD is dupilumab, and, you know, the Achilles heel, if you will, is that Q2-week dosing. A two to three-month would be really interesting here. Now, I guess, do you plan to look at additional indications beyond AD for bosa?
No. You know, as we, as we mentioned previously, you know, we have a company, CTTQ, that had a previous relationship with Biohaven, that's investigating the respiratory indications. There's a phase III trial ongoing in severe asthma. There's a phase III in chronic rhinosinusitis with nasal polyps, and there's a phase II ongoing in COPD in China by that partner. We took on the AD in the derm setting, and if it showed great data, you know, we would look for partners and move forward with that potentially in that indication. It'd be hard to walk away from it if it really showed anywhere near the same kind of data we showed in the phase 2a.
You know, I think potency is driving that, and that's why we included that antibody, the TSLP antibody, in the bispecific. As a best-in-class TSLP, combined now with the IL-4R binders, we believe that our bispecific will also then be a best-in-class.
Perfect. Perfect segue then to ATI-052. As you said, that's a bispecific with the TSLP component being based on bosa, and then the IL-4 alpha, blocking capability as well, you know, sort of mirroring, the Dupi pathway directly there.
Mm-hmm.
You know, you've done a phase I SAD mat study with that candidate, could you just highlight what you've shown today in terms of safety, PK there, then how you know, are thinking about exploiting that? Obviously, you have some now phase 1b studies ongoing.
Yeah. Yeah, we were quite excited when the data came in on the healthies. Usually, a phase I healthy volunteer study is ho-hum. You just try and show safety and tolerability and some pharmacokinetics that make sense to move the program forward. In our case, because it's an IL-4 receptor-mediated binder and you have TMDD, where the drug gets cleared, we made sure that we could offset the TMDD response with a YTE mutation in the Fc, and that extends the half-life, or potentially extends the half-life. We didn't know if it would because of the receptor-mediated disposition. We were quite excited when we showed that we had a 26-day half-life with that molecule.
That's, you know, to your earlier point on Dupi, you know, we are three times longer half-life than Dupi and even lunsekimig, a potential competitor from Sanofi, that has a TSLP IL-13, also with eight- or nine-day half-life. 26 days really allows us to have duration of response, that could extend out also eight or even up to 12 weeks, depending upon the dose that we would take forward. We're excited about not only that, but what really was compelling to move into the phase I was our potency and activity that we saw in an early PBMC assay, where we compared the potency of ATI-052 to the combination of Tezspire plus Dupi.
We showed that we're 4x more potent than the combination in inhibiting a TSLP IL-4-activated PBMC populations in a TARC response. We know we have a very potent molecule. We now know that we have a very long half-life for an IL-4R receptor mediated target. In the pharmacodynamic evaluation that we did, we did a target engagement assay, where we added in either IL-4 or TSLP into whole blood from samples taken from the healthy volunteers. Ultimately, we showed up to six weeks of 100% inhibition of the TSLP response at 360 mg dose. Again, up to about three weeks of 100% inhibition and almost complete inhibition up through six weeks for the IL-4 activated response.
Not only is this molecule long-acting and long duration of activity, but really, we think that the PK/PD could even show a substantial benefit now as we move into the 1bs. We'll evaluate that. In order to really understand the true value. The safety profile was great. We didn't see any safety related to the molecule. We saw no conjunctivitis. And ultimately, the AE profile was all grade one, and we were excited about not only the PK, the PD, and the safety in order to move into our phase 1bs.
Excellent. As you mentioned, the phase 1bs, you have a study in it ongoing in atopic derm and the phase 1b I have for asthma starting the first quarter. Just, I guess, in terms of what you're looking to see out of those studies, and again, top-line data, do you think this year as well?
Yeah. I think Jesse's gonna talk about the 1bs.
Yeah, happy to do that. Jeff, yeah, you're absolutely right. Building on the success of the healthy volunteer study, what we've done is we've initiated two phase 1b studies. The first that we announced in January was the atopic dermatitis study, and then just earlier this week, we announced the initiation of the asthma study. We're continuing to execute across the program for O-52. Let me take you back to the AD study. The AD study is a patient population with atopic dermatitis study. The baseline EASI score is a 21, we're enrolling a more severe patient population into the clinical study than, for example, the bosakitug study, which has a cut-off of 16.
That's primarily driven by the fact that we're enrolling a total of 12 subjects into that clinical study with a three to one randomization, so nine on active, three on placebo. We wanna make sure that we're enrolling a patient population with severe disease or high, moderate to severe disease to ensure that we can see a dynamic response in those nine patients that will receive active drug. The dosing for that atopic dermatitis study is gonna reflect very closely what we did in the multiple ascending dose of the healthy volunteer study. Over a 28-day interval, we'll be dosing 480 milligrams, a total of 5 x.
After that last dose at day 28, we're going to follow subjects out to day 57, approximately 28 days after the last dose, we'll assess the primary endpoint, and we'll be looking at outcomes EASI, BSA, IGA, standard outcome measures. In addition, in that clinical study, we're going to be doing a lot of work from a PD perspective, including tape strips. Tape strips, we have a lot of experience there working with Emma Guttman-Yassky's lab. We worked with them with the ATI-2138 program, we think that we're going to have the opportunity to assess the proteome and looking at the significant PD markers for that patient population, not only over the dosing period, but we're going to extend follow-up out to day 141.
We think we'll have the opportunity to look at long-term PD responses. You guys are probably familiar with the work that Emma Guttman-Yassky has done with DUPI. There's a lot of work that has been done on DUPI, and we think we're gonna have the opportunity to look at the potential additive effect of inhibiting TSLP in this patient population. There's gonna be a very rich data set coming out of the AD study, and we're really excited that that is ongoing and progressing to plan. Moving to the asthma study. The asthma study, we're gonna enrol a total of 16 patients with moderate disease, and I say moderate disease. This is gonna be GINA step two to four, really a firmly moderate patient population.
Total of 16 patients, same randomization, three to one, we're gonna have 12 active, 4 placebo. We're gonna give them a single dose of 480 milligrams at baseline, and then we're gonna assess the primary endpoint at day 28. That primary endpoint will primarily involve FeNO reduction and FEV1 improvement. We're looking at a patient population that's TH2 high in this clinical study, the initial clinical study, with a FeNO cut-off of greater than 35. The reason we're looking at the TH2 high patient population is it's a smaller patient population. We wanna make sure that we're seeing dynamic response in that TH2 patient population, but we still do think that there's potential for the product, given the fact that we're inhibiting TSLP in that TH2 low.
That's a patient population that we'll explore in the later phase II studies, as well as the phase III program.
Just a quick clarification on the dosing in the AD trial, three to one randomization, how many patients again?
For the AD study, there'll be a total of 12 patients that will be randomized, nine active, three placebo.
single dose, 480 mgs.
For the AD study, it will be a single dose that's tested, but that single dose will be administered a total of 5 x over the 28-day interval. Baseline, day seven, day 14, day 21, day 28.
I'm just trying to wrap my head around, given what you anticipate, given the PK/PD there, why are you looking at dosing so frequently in the AD study?
Yeah, it's a great question. The first goal there was to make sure that we're dosing in the AD study similar to the healthy volunteer study, because what we're doing is we're building out our POPPK model, that POPPK model will inform our dosing strategy for the larger Phase 2b study, then obviously moving into the Phase III program. Having a similar dosing schedule, having a similar sampling schedule to the MAD study, we think will really provide a robust data set to inform that POPPK model. Now, we're dosing weekly in this initial study.
Our plan, based on the data that Hugh has discussed, is to have a dosing interval at minimum between two and three months, based on the extended PK that we're seeing with 052, as well as the extended PD response. This is an initial study that's gonna allow us to inform the POPPK model, which will give us a really robust data set in order to inform dose and dose frequency for our subsequent studies. Hugh, anything you'd like to add there?
Well, I would just say, you know, Jesse mentioned this, it's all EASI or higher, so it's only severe patients. We're also gonna be able to really understand how potent our molecule really is. That's another, you know, goal.
Okay. As you then think about 052, you know, you're gonna have efficacy in a derm as well as a pulmonary indication, really opens up a very broad opportunity with that initial proof of concept data. Again, data anticipated second half of the year for both of these. Is that correct?
That's correct. We would anticipate data for both of those clinical studies second half of the year, potentially even reading out prior to the bosakitug AD study.
Assuming both of those are positive, you have the opportunity to then really look at an expanded universe of pulmonary and dermatologic indications. Obviously, Dupi has a plethora of indications on the label, and I think added another one yesterday or the day before. What do you need to see to move ahead? I guess, what is the bar for success here? You've got the PK/PD differentiation, likely, you're gonna have efficacy, but at a very sort of, high effective dose in the AD study. What do you guys want to see to be comfortable to then move ahead and to call it larger phase II real efficacy, you know, larger efficacy studies?
Do you want me to take a shot at that?
Sure.
Okay. Yeah, no, I think we're gonna have a really unique opportunity across the clinical program. With the 052 studies reading out at a similar time to ATI-045, we anticipate both of those programs are gonna be successful based on the data sets that we have. We have significant optionality, and, you know, as we start to read that data out in the second half of the year, I think we're gonna start to make some prioritizations. We're really excited about 052's potential in asthma, and that's from a couple of potential reasons. We're neutralising two of the primary drivers of asthma, and there's two approved therapies there. Obviously, you have Dupi as well as you have tezepelumab.
If you compare what we have in 052, for example, to dupilumab, you have a product with dupilumab that's a great product. It's demonstrated efficacy and safety. It's administered over a two-week interval. We feel we have a dose frequency benefit as compared to Dupi. In addition to that, because we have the TSLP component, we have the ability to target patients with T2 low. Not only are we gonna pull in the patient population with T2 low, but we have a potential dosing frequency benefit. If you look at the TSLP inhibitor, tezepelumab, not only do we feel that we have the potential to have a dosing advantage in that patient population, we also have the IL-4 additive component.
We think that we have the potential to have deeper responses, as well as across a broader patient population, as well as with that molecule opening up the potential for atopic dermatitis. We just think we have a broader potential suite of indications for the molecule as compared to the approved therapies, as well as potentially in development. Hugh, I don't know if you want to add anything to that.
That was good.
I guess this brings to mind the question of: Okay, if, you know, second half of this year you have positive results in bosa and AD as well as your bispecific, what do you do with the monospecific?
Yeah. No, it's a great question, and, I hope we're in that position and we, and we have that difficult choice to make. I don't think it's gonna be as difficult as it is on when you look at it at first blush. We are very excited about ATI-052. We think the primary indications for ATI-052 would likely be in asthma and atopic dermatitis. If you look at if we have a TSLP inhibitor that is demonstrating benefit in atopic dermatitis, I think what we've done is we've proved out the fact that, number one, we have a best-in-class TSLP inhibitor. There are options or opportunities to explore that in a monotherapy fashion, as well as
Are there rational combinations that we can make with a best-in-class TSLP inhibitor in other indications, where TSLP, as well as other, cytokines, are driving the main pathology? I hope that's a decision that we have to make, Jeff.
Okay. Now, you'll have a lot of interesting data in the second half of this year, and a lot of reasons to believe it'll be positive. Really exciting there. Just glancing at time, because I'm not paying any attention whatsoever. Okay, that leaves us only five minutes to talk about the small molecules, which are also really exciting. ITK has gotten a lot of attention recently from the Corvus data around their AD update recently. We cover Corvus, as you know. Your initial program is an ITK/JAK3 inhibitor. You've shown positive data there as well. You have the JAK liability, if you will. JAKs obviously work well. They're approved in AD, but you have the potential warning label issues.
I guess, as you think about your ITK/JAK program, how do you think about indication selection there? I know I think you mentioned today some preclinical data in alopecia. How do you think about indications for the ITK/JAK3 program? Obviously, following this, you have an ITK-selective program that's a little earlier, so maybe talk about those.
Sure. I'm happy to take this question. Yeah, you're absolutely right. We're thrilled about the Corvus clinical data, and then also the clinical data we generated with our first-generation ITK/JAK3 dual inhibitor, ATI-2138, because both of them really validate ITK as a really great target for I&I indications, in particular in atopic dermatitis, for now. The way we think about ATI-2138, I already mentioned it's an ITK/JAK3 dual inhibitor. I think, clearly, ITK and JAK3 expression is limited to the immune system. We believe that, again, this compound is a much better safety profile than other JAK inhibitors.
JAKs are widely expressed in many different organs and tissues, and indeed, that's what we have shown in the six and nine-month chronic tox study, as well as the clinical data we have generated with that compound. As we think about the lead indication for 2138, we wanna find an indication where we have a good mechanistic fit. I think also an indication that offers a little bit of white space, which is not too heavily covered by other JAKs. Alopecia comes to mind. There are also recalcitrant forms of alopecia we may wanna expand into.
Indeed, we just recently disclosed preclinical data in a very severe model of alopecia, in collaboration with Angela Christiano at Columbia University, where we have shown that 2138 indeed is improving hair regrowth in that model the fastest and in the most pronounced way. According to Angela, she's never seen something like that before. That's what she told us. Alopecia is a possibility. I think we'll select the lead indication by the end of this quarter. We are excited moving 2138 forward. You mentioned the next-generation ITK compounds we're working on, and this is indeed also a big emphasis in the company right now. Very excited about it.
What we are trying to do there is dial out the JAK3 cross-reactivity, keeping in mind the safety liability associated with the JAK class in general. We are doing this while we are maintaining the high potency on ITK that we have in 2138, and we have achieved both of these challenges. We can dial in TXK, which is a cysteine kinase, and our lead compound in the ITK-specific space is ATI-9494. That's indeed an ITK/TXK potent inhibitor. We also focused on improving the PK profile of the compounds for once-a-day administration, and this is what the preclinical data would predict in the moment. The compound is currently in IND-enabling toxicology studies, and we are aiming for an IND by the end of this year.
The way we are thinking about ITK, in short, is JAK-like activity with a better safety profile. ITK probably has a much wider reach than something like a STAT6 degrader, which is very Th2-focused.
Wonderful. No, I think that's a great summary of the programs. Really exciting target, obviously, and looking at ways to really maximize the next generation compound there. Unfortunately, I think that we are up on time, and we could probably keep going for another half hour, really appreciate the time this morning. Really exciting programs with a long list of catalysts as we get into 2026. Really looking forward to following the story there. Gentlemen, I hope you have some excellent meetings today. With that, thank you very much.
Thank you for having us.
Thank you, Jeff.
Have a good day. You too.