the trial. And then of those 92, 31 went on into our 16-week extension. We do follow every patient who was enrolled into the study for that 24-week off treatment. And with respect to the phase 3, the most important for us is after 52 weeks of treatment on the phase 3 alopecia areata registrational study, we will continue to follow those patients in a long-term extension study. And these data will really help to instruct should treatment continue to be on an every two-week basis or can we extend that frequency in a maintenance period to a longer time point such as dosing once a month. So we're really excited to look at those data so we can have more clarity on treatment after 52 weeks in our Phase III program. You know, likewise, in the first quarter of next year, we will have 52-week off-treatment data for our atopic dermatitis Phase IIb study, and in that, again, we're really looking to instruct what should the dosing be after 52 weeks of treatment, and, you know, should or are there patients that experience durability of responses beyond, say, a dosing interval that we evaluated in the Phase 2B, such as Q monthly and every three monthly. We did see, of course, in our Phase 2B that patients experienced great durability and many experienced a deepening of response. Now we want to look at, in this 52-week off treatment, how those responses are maintained and the durability of those responses to see if it's feasible to extend that dosing interval beyond quarterly.

Thank you so much, Mary, for the thoughtful color.

Thanks, Yaz.

Thank you. Our next question comes from Samantha Semenko from Citi. Your line is open.

Hi, good afternoon. Thanks very much for taking the question. And thank you for all of the details in the recent market research that you shared in Atopic Derm. I'm just wondering if you can elaborate a bit more on how physicians are thinking about prescribing ResPeg in the first-line setting. Are there certain patient population or patient characteristics that physicians are identifying that are best suited for ResPeg? And did your market research give any indication on the breakdown of proportion that would be candidates, say, for first line versus second line or later? Thanks very much.

Yeah, very good question. Look, the market research that we did was extensive, and we want to understand how to position our drug. because at some point it is a completely novel mechanism and everybody thinks that there's going to have to be a step through through IL-13s to ultimately get to something like a T-reg mechanism. And we don't find that to be the case. I think overall, as I said earlier, there's only about 10% of the population with ectopic dermatitis that's being treated with systemic therapies. So it's an enormous upside market potential. And even the patients that are getting IL-13s, which is sort of the gold standard right now, I think about half of those patients either don't respond or fail after a year or so. So there's lots of opportunity for RESPEG as a first-line indication. Clearly, as a second-line indication, it fits that definition perfectly, since we know how many patients fail IL-13, and with a quarterly maintenance dosing regimen, it makes it a very easy drug to take for those patients. But I do think we'll get a significant share of the first-line market as well once patients get experience. Remember, it doesn't cause any infection. It doesn't cause conjunctivitis, and those problems, those side effects are potentially much more serious than mild to moderate self-resolving ISRs. So, overall, we're pretty happy about getting our first-line market share.

Thanks very much.

Thank you. Our next question comes from Jay Olson from Oppenheimer. Your line is open.

I'm sorry, I barely heard that question. Could you say it again louder?

Thank you, and we'll take our next question.

Our next question comes from Cha-Cha Yang from Jefferies. Your line is open.

Hi, team. This is Cha-Cha on for Roger. Thank you so much for the updates. It's always very informative and very colorful. I was wondering if you could give us some comments on the pre-trial that happened last week, any color that you can give on the outcomes of that, and then what impact you expect those outcomes to have on your upcoming September trial. Thank you.

Yeah, look, always a good question. But of course, we can't really comment on an ongoing litigation. I can tell you that the trial is scheduled, a jury trial is scheduled in federal court in San Francisco for September 8th. And we believe we have a very strong position. And that's unfortunately all I can tell you about it at this point.

So I'd love to give you more, but it's difficult to comment on ongoing litigation. thank you our next question comes from arthur hay from hc wainwright your line is open hey hall and team congrats on progress and mary congrats get the the single trial for the a study sign off um so um for that part i just wonder for the off drug data in the fourth quarter for the patient who finished the only

finished the 36 week are we good also looking to the data from those that part of patient there yeah hi Arthur yes we will be looking at those patients as well as those patients that completed the 52 weeks of treatment obviously I I think what will be most instructive and valuable to our decision-making will be those patients. There were 31 of them that went into the long-term extension, went into the 16-week extension. But we will be looking at all the 92 patients that we randomized into the study and providing an update on the totality of the findings.

Okay, thanks. So just one quick spacing. So, when you're talking to the FDA, do they put some requirements for a medium or minimal duration for the current episode for the alopecia patient?

Yeah, thank you for asking. We will be following the same convention as JAK inhibitors, and our study design did provide for patients that have up to eight years of their current episode. We do know that there are some other people who've looked at a more enriched patient population that only have a current episode of up to four years' duration of their current episode. However, we don't think that reflects the actual population of patients with alopecia areata, and we want to have a very broad label. So we did design a study that will include both patients who are JAK inhibitor naïve and JAK inhibitor experienced. We'll have adolescent patients as well as adult patients, and we will be looking at patients who have a duration of their current episode less than four years and four to eight years. We think having the broadest label has the greatest commercial potential as well as serving the broadest proportion of patients and certainly a study that's in line with the prior JAK inhibitor studies.

Awesome.

Thanks, Artur.

Thank you. Our next question comes from Mayak Mumtani from B. Riley Securities. Your line is open.

Thanks for taking your questions and I appreciate all the level of detail. Two-partic question. On the EADV, what's the incremental data set that we should expect and if there's a chance off-treatment Resolve AA data could also be presented because it's October 1st, technically post-quittered. And I also could help with the, you know, enthusiasm for enrollment in your global alopecia phase three. And on the maintenance, atopic derm data should, you know, just based on your phase 1B where we got EZ75 up to nine months, can you just highlight what are the differences in this off-treatment versus what we saw? in your phase 1D, and should we also expect to see some of the EZ100 responders keep that off-treatment remission?

Thanks, Mayank, for your questions. Certainly, as GZ mentioned, we're really pleased to have the two oral presentations accepted at EADV. I think this really highlights the promise of our novel mechanism of action and, of course, the strength of our clinical data. We, you know, when we submitted the abstracts, of course, we did not have the 24-week follow-up data, and therefore, of course, our abstract doesn't include this portion of our study. The study is still ongoing and blinded. Now, that being said, we, you know, it is possible that we could include the 24-week data. As you mentioned, this could be very valuable and of significant interest. We cannot make that decision today. If we do have the data readout in time and we are ready, we would love to include those data as well in our oral presentation by Dr. David Rosemarie at EADV. But again, at this time, we can't make that commitment because the trial is still ongoing and we haven't even locked that part of the database. But thank you for asking. It is a possibility, but, again, it's not in our abstract. With respect to your second question about the maintenance data and the data of 52 weeks off treatment for the Phase 2B and atopic dermatitis, you're correct, we did show off treatment data from our Phase 1B for nine months. The difference here is now we'll have three additional months of follow-up post-withdraw from drug. And, you know, we think that this is extremely important to us to look at, again, that durability of those responses. And, again, we'll be able to look at the EZ75 and, as you mentioned, the EZ100 and the EZ90. you know, we did see consistently that patients continue to improve with ongoing ResPeg treatment, and we did see this deepening of response. Now we want to look at, you know, these patients being off treatment, and we will be able to look at the nine-month time mark like we did in the Phase 1B as well as 52 weeks off treatment. And this will be extremely valuable to look at the optimal dosing And after 52 weeks of treatment, can patients have less frequent maintenance dosing? And for some patients, that could be longer than every three months. So, we're really excited to look at those data and really, you know, closely examine the durability of those responses. So, thank you for asking those two questions.

Very helpful and comprehensive.

Thank you. Our next question comes from Julian Harrison from BTIG. Your line is open.

Hi, thank you for taking the questions, and congrats on all the recent progress. First, I'm wondering if you have any updated views on ResPeg's competitive positioning in alopecia areata in light of a recent data set last month from another non-JAC treatment option in development in the broader space. And then, taking a step back, keeping in mind ResPeg's pipeline and a product potential, I'm wondering if you've thought at all about supporting any signal-seeking efforts on an IIT basis. I'm sure you've gotten some investigative requests. Is that something you're open to? Are, you know, our future trials, you know, best to keep, you know, full control of Ednectar? Thank you.

Yeah, two very good questions. So, first of all, regarding, you know, competition in alopecia areata look the the the study uh that was just uh released data that was just released and i'll let mary comment a little more on this very little difficult to interpret and and it you know it was also a single arm study so it wasn't a blinded study it's a little difficult to interpret and and quite frankly it had a patient population that was much less severe or much earlier on in their disease than what we're planning i think mary did talk about the difference between four years and eight years and I'll let her comment on that in a moment and to your second question about looking at other indications yeah we are we are in the process of considering which indications we would like to do some pilot studies to get some proof of concept studies thing look we were we were very successful in the lupus study when we when we looked at the data on a weight-based dosing rather than a fixed-based dosing. And I think there's a potential for working in cutaneous lupus as well. And there's a number of other indications, just as we're doing in type 1 diabetes, that could warrant a, you know, whether it's an investigator-sponsored trial, you lose a little bit of control there perhaps, or it's our own pilot studies. I do think that to support the value of a TREG mechanism, I do think there's other indications that we will be looking at. I'll let Mary come back to your first question for some more insight.

Yeah, sure. You know, Howard mentioned this in our prepared remarks. We view the alopecia areata market as very large, and, you know, certainly these patients are underserved by JAK inhibitors. So I think as seasoned biotech executives, clinicians, and scientists, we love innovation, and we love to see innovation in a space where there's, you know, huge potential for growth. Now, that being said, as Howard mentioned, the Q32 results are really difficult to interpret. You know, it was a small, only 33 patients, open-label study with no placebo, and, you know, as we've mentioned now twice, you know, enrolling a selective patient population and restricting eligibility really skews results in the favor of any drug that's being tested. You know, by contrast, our phase 2B study was randomized. It was placebo-controlled. We looked at more than one dose. We allowed a broad patient population that was consistent with JAK inhibitor studies, so the generalizability has greater potential. And, you know, we had a very standard Phase 2B trial that then was recognized by the FDA as being sufficient to move forward into a Phase 3 study. So ultimately, you know, we remain very encouraged by our efficacy and safety profile, and I know the dermatology community at large is really looking forward to beginning enrollment in our study in the first quarter of next year for these reasons. So thanks for asking.

Thank you. Our next question will come from Mark Fromm from TD Cowan. Your line is open.

Thanks for taking my questions, and congrats on all the progress and getting the Phase III up and running. Maybe just, Howard, you touched a little bit about kind of the different unmet needs in the AD market, particularly, you know, as you think about treatment naïve versus experienced patients. Just how do you guys view that as likely to kind of impact the relative enrollment pace for these Phase 3s and the two different kind of flavors of Phase 3, you know, different patient sizes, but also, you know, different levels of unmet needs?

Yeah, good question. I certainly think, look, with the absence of OX40s, it certainly limits the opportunities for new mechanisms of action. And I think, you know, RESPEG is obviously unique in that sense. So I don't think patient enrollment will be an issue there. I think it'll actually go fairly quickly. I can't tell you exactly what it'll look like. We just started the studies, but I'm hopeful that it goes fairly quickly, recognizing that as a new mechanism goes, there's really nothing else at the moment. We'll see what the STAT6 data looks like, upcoming data. But I don't think that's as complete a mechanism as RedSpeg. I can let Jay-Z comment on that a little bit if he'd like. But overall, I think the market, I don't think people understand how large this market is. Let's assume the market by 2033 is probably $35 billion, and that's 10% of the patients getting treated. So I think, look, there's other good drugs out there. I mean, Apogee's drug is certainly a good drug. I think STAT6 could be a very important mechanism. But the fact of the matter is, the market is enormous. And if you have a novel mechanism, you should be able to get a reasonable market share of a market that at 10% of the patients being treated is already planned to be $35 billion. I'll let Jay-Z comment a little bit on why we think ResPag is probably one of the best opportunities in treating a disease like A.D.

Yeah. Hey, Mark. And thanks, Howard. Yeah, I mean, I think that this point was touched on briefly at first. I mean, one of the things that our market research showed us is that we would have good first-line penetration. And that's really because the pretty much the entirety of the available approaches that physicians have, and even the pipelines, including agents like STAT-6, they're really all targeting the same pathway, right? They're in a very Th2-dominant, a inhibitory state. They may be acting on more than one node, but they're acting really on the singular pathway. And our market research really showed us that a new MOA was extremely important for physicians. Many indicated they would use a new MOA first. And so we think this will really help position RESTPEG nicely. As you heard about our Phase III study design, they're really taking advantage of not just what we've learned, but really even strengthening, you know, on where we saw the greatest differentiation in our Phase II data, and they're pushing that even more to give RESPEG a really big opportunity for a very highly differentiated label at the end of this registration program.

Thanks for the question. Thank you. Our next question comes from Jessica Fai from J.P. Morgan. Your line is open.

Hey, guys. Good afternoon. Thanks for taking my questions. Can you expand a little bit on your expectations for ResPeg's effect size in biologic experienced patients compared to biologic naive patients in AD? And how should we think about benchmarking the biologic experienced AD phase 3 trial that you're running? Is EBCLIS a good comp there, or if not, what should we think about?

Okay, thank you for the question. It's a very good question. I'll let either Jay-Z or Mary answer it in a little more detail, but I can tell you that we looked very closely at whether there's any biological reason, any mechanistic reason why a patient who fails IL-13 would not respond to a completely different mechanism, and we couldn't find one. So I think we should be successful in treating experienced patients. I'm going to let Jay-Z and Mary comment a little more on that.

Yeah, I can just start, and Jay-Z can finish. Yeah, Jessica, I think you're bringing up a very important point. Leberkizumab was studied in the ADAPT study, and these were patients treated with Leberkizumab after Dupixent, and there was no diminution of efficacy. 57% of the DUPI-exposed patients who were treated with Leverkizumab had an EZ75 at week 16. And in the Leverkizumab Phase 3 studies, the Advocate 1 and the Advocate 2, the EZ75 at week 16 was 52% and 59% in that naive population. So, you know, we and the ADAPT study did include patients who also had an inadequate response to DUPI. So, you know, given this precedence, this trial data, and the RESPEG mechanism of action that augments the regulatory networks rather than just blocking a single downstream inflammatory mediator, we do expect the efficacy in the biologic and JAK inhibitor experience patients to be very similar to the naive patients. And I'll let Jay-Z expand, you know, further if you want on the mechanism of action, Jay-Z.

No, thank you. And I think you touched on a lot of the key points that, you know, our mechanism with the Treg induction, if anything, is meant to really help patients for whom inhibition of IL-13 or IL-4 and 13 is no longer adequate, right, to control their disease. This is one of the greatest features, right, of a Treg approach is it acts upstream of all of those factors. And we look forward, you know, to continuing to elaborate on this. You raised a very important point, which is that while the ADAPT study is useful, as Mary explained, it's an open-label single-arm study. And so, there hasn't really been a true benchmark published, for example, for placebo in this patient population. So, all of these are all things that are going to be components of some potential data to be reported. if Sanofi reports the results of their LITLAMAB study in this patient population, that was designed as a randomized control trial. That will create one important piece of information for the placebo. But overall, we're extremely excited to have this third study as part of our registrational program. We expect RESPAG, you know, has a very, very good opportunity to be efficacious in this patient population for all the reasons we've explained. And with a study like that under RESPEC belt as part of our BLA, it really allows us to have a much more differentiated label for RESPEC.

Thank you. Thank you.

And our next question will come from Andy Shea from William Blair. Your line is open.

Thanks for taking our question. So, Howard, you mentioned about the physician survey that you did. It's super helpful for you to share with us. I'm curious if you have probed the group about durability as a means for differentiation. Is there a time that these physicians are looking at either the three-month or six-month timeframe? And my second question has to do with the type 1 diabetes trial that you're running with trial net. It seems like ResPeg is being treated for six months, but the primary endpoint is measured at 12 months. So can we infer from that that there is a little bit of off-treatment effect that we can extrapolate from the trial? Thank you.

Sure. Very good questions. I'll let Mary answer the question regarding the TrialNet type 1 diabetes study. I can tell you from our market research, time duration for onset of action was important, but the most important thing is long-term durability, and you could see that if you look at our maintenance data, the results keep getting stronger and stronger, and I expect that they'll continue that way. I think one of the other things that was very important to physicians was a manageable side effect profile. And as I said, ISRs didn't concern them at all. They were actually much more concerned about infections and conjunctivitis than they were ISRs. But overall, a durability of response that continues to improve was very important to the physicians. Mary, do you want to take the question on the type 1 diabetes trial?

Thanks, Howard. I'll actually do that. So, yes, I want to describe a little bit about how that study is designed. So, if you recall the tipulizumab studies, you know, the CD3 antibody. So, you know, the way that works is it's a very short treatment course, right? It's just a few cycles at the very beginning. But that actually is enough to alter the whole trajectory of the disease. So, Tronet was very excited that they could dose longer with ResPeg, that they did with teplizumab, so that was exciting for them, and so they selected a six-month course. The mixed meal tolerance test and C-peptide levels, they're measured throughout, through a year, so they're measured both during the treatment as well as the six months after the treatment, but again, the whole theory and understanding of the disease, its progression and the worsening that people have is it's well understood that a course of intervention will change the whole slope of the disease and provide the therapeutic benefit that we're looking for. So that's why the study was designed this way. It's very much right in the sweet spot of how these kinds of type 1 diabetes studies are done.

Thank you.

That's helpful. Thank you. Thank you. And I'm showing no further questions from our phone line. I'd now like to pass it back to Howard Robin for any closing remarks.

Well, thank you, everyone, for joining us today. And it's not often that a company develops a new MOA that has the potential to greatly help patients in need. And I want to thank our employees for their diligence and commitment, and also our shareholders for their continued support. So stay tuned, and thank you very much again. Good afternoon.

This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.