Howard Robin: powerful translation of the scientific discoveries that led to an understanding of the importance of Tregs and to the first demonstration of their clear clinical efficacy in autoimmune disease. The Nobel Prize in Physiology or Medicine was recently awarded for these discoveries that established FOXP3 positive Tregs as key enforcers of immune tolerance. We're very humbled that the Nobel Committee included the publication of the Phase 1b data for RESPEG in ectopic dermatitis and psoriasis as support in the background documents for this award. The recognition of RESPEG was truly an honor and speaks to the journey that our nectar scientists and clinicians have traveled over the years to turn important scientific discoveries into real potential medicines for patients. Our approach with RESPEG and stimulation of Tregs is highly differentiated in the field. We believe this is why we've been able to uniquely generate meaningful and robust clinical data that clearly support continued development of this novel modality. Respeg was designed to closely mimic the way Tregs in our own immune system work to resolve inflammation. Its construct gets closest to emulating natural human biology, achieving this through IL-2 agonism, with native sequence IL-2 receptor interactions and a validated chemistry approach, PEGylation, that has led to over two dozen approved biologics. At the 2025 EADV Congress in September, we presented compelling results from the 16-week induction period of the 400-patient resolved AD study of RESPEG in moderate to severe ectopic dermatitis. These data showcased the clinical differentiation that could be achieved with this novel MOA, and Jay-Z will touch on this later in the call. And this weekend, at the 2025 American College of Allergy, Asthma, and Immunology Annual Scientific Meeting, we will present data from a pre-planned analysis of ectopic dermatitis patients from the RESOLVE-AD study who also had a history of asthma. These data provide further basis for differentiation of RESPEC. Recently approved and in development IL-13 selective pathway blockers and OX40 pathway blockers have shown limited potential to help the asthma symptoms in patients with both ectopic dermatitis and asthma, which is a comorbidity in 25% of all ectopic dermatitis patients. And so we're very excited about these new data. In Q1, we will present 52-week maintenance and escape arm data from the RESOLVE-AD study in ectopic dermatitis. The maintenance arm data in particular will be an important look at continued treatment with RESPEG in patients who have established an easy 50 response at the end of 16 weeks of induction treatment. There remains a need for novel mechanisms beyond those available currently in the treatment landscape for ectopic dermatitis patients. In the U.S., there are over 15 million people with moderate to severe ectopic dermatitis, and fewer than 10% are receiving biologic treatments for this chronic skin disorder, with many patients not responding well to the existing agents. We believe that this market will grow with the adoption of novel mechanisms, as was seen with the induction of new mechanisms in the evolution of the psoriasis market. We expect to hold an end-of-Phase II meeting with the FDA before the end of this year to review our Phase III plans for RESPEG in moderate to severe ectopic dermatitis. Importantly, in December, we plan to present the top-line results from the Phase IIb Resolve AA study in patients with alopecia areata. This study enrolled approximately 90 patients with severe to very severe ectopic alopecia areata, With strong phase two results in the dermatological setting of ectopic dermatitis, we're optimistic about the second dermatological setting for RESPEG. Nearly 7 million people in the U.S. have or will develop alopecia areata, and over a million of these patients have severe to very severe disease, according to the 2023 population-based cohort study. Patients with severe to very severe disease alopecia have limited treatment options. The only FDA-approved systemic treatments for alopecia areata are JAK inhibitors, which carry multiple well-known black box warnings and are associated with high relapse rates upon discontinuation. In a 2024 survey of 131 US-based board-certified dermatologists, a majority of physicians said they were uncomfortable prescribing a JAK inhibitor And more than half of these physicians reported they would try alternative therapies prior to prescribing a JAK inhibitor. With this backdrop, RESPEG could be introduced as the first biologic in the setting of alopecia areata, representing an additional billion-dollar market opportunity. And so we look forward to these upcoming results from the 36-week treatment period of the RESOLVE-AA study expected in December of this year. In immunology, our partner TrialNet recently initiated the phase two study of RESPEG in type one diabetes. This study, which is funded and sponsored by TrialNet, will evaluate RESPEG in new onset stage three type one diabetes patients. Jay-Z will update you on our other programs as well as our lead pipeline antibody, a TNFR2 agonist that has a unique tissue-specific Treg and Breg stimulator profile. Because of its monomeric activity, we're now building a bispecific program based upon this mechanism, which combines it with validated antibody targets in immunology. Our goal is to advance one of these antibody programs into the clinic next year. And with that, I'd like to turn the call over to Jay Z to review more details on RESPEC's ongoing Phase IIb studies and our early pipeline programs.
Jay Z: Jay Z. Jay Z. Thanks, Howard. And thank you, everyone, on the call for joining us today. To begin, I'll remind you that earlier this year, the Resolve AD Phase IIb results demonstrated the promise of Nectar's novel approach to the IL-2 pathway. The global study randomized 393 patients with moderate to severe atopic dermatitis to receive subcutaneous treatment with three doses of Respec, a high dose of 24 microgram per kilogram every two weeks, a middle dose of 18 microgram per kilogram every two weeks, and a low dose of 24 microgram per kilogram every four weeks, or placebo every two weeks, for an induction period of 16 weeks. Following week 16, RESPEC-treated patients who achieved easy reductions of 50% or greater were re-randomized to continue at the same dose level on a Q4 week or Q12 week regimen for an additional 36-week maintenance period. In our June data disclosure, we reported that the study achieved statistical significance on the primary endpoint at week 16 for mean percent change in EZ score from baseline for all RESPEC arms versus placebo. And the study achieved statistical significance for key secondary endpoints at week 16 of disease reduction including EZ-75, EZ-90, HNRS, the VIGA-AD, and BSA. we have yet to see a plateau in the efficacy response in the RESPEG treatment arms. This study is currently ongoing with two additional upcoming data readouts that Howard mentioned. The first will be the 36-week maintenance study results, which compare treatment with RESPEG at either one-month or three-month dosing intervals out to a full year, which would be the intended maintenance-based dosing regimens following the 16-week induction period. And the second readout will be the one-year off-treatment data expected in the beginning of 2027, which will measure the potential remittive effect of RESPEC in atopic dermatitis. In the meantime, we continue to add to the compelling data set from the RESOLVE-AD study, including the data we shared from the escape arm of the trial at this year's EADV Congress. As a reminder, the study design allowed for patients who originally received placebo in the 16-week induction period and achieved less than easy 50 at week 16 to enter into an open-label treatment escape arm to receive the high-dose RESPEG regimen for a treatment period of up to 36 weeks. The data presented at EADV demonstrated a deepening of responses in these patients with continuous treatment with RESPEG and support a 24-week induction period for our Phase III program. As Howard stated earlier, we are presenting additional data in patients with asthma from ResolveAB in the late-breaking oral presentation at the ACAAI meeting being held in Orlando, Florida, this weekend. In addition to the asthma data that I'll discuss in a moment, that presentation will also give an update on the placebo crossover data We're now all but one patient have crossed 24 weeks of treatment with 24 microgram per kilogram RESPEG Q2 weeks. We will also cover additional endpoints such as EZ90 and itchNRS. In addition, the presentation will show a forest plot demonstrating the consistency of RESPEG efficacy across multiple subgroups. This important finding prepares us for phase three. Given that one in four patients with atopic dermatitis also have asthma, we designed the study in advance to evaluate its effect on symptoms of asthma using the validated five-point asthma control questionnaire, also known as the ACQ-5. These data include a pre-specified exploratory endpoint for the subset of patients in Resolve AD that also had asthma, including those with moderate and uncontrolled asthma. at baseline. The ability to improve comorbid conditions is a substantial factor in clinical treatment decisions for atopic dermatitis and could expand the potential market opportunity for RESPEC in this setting. We know that beyond dupixent, neither trelekinumab nor lebrekizumab has been able to show an improvement in asthma symptoms in patients with atopic dermatitis. And this extends to the OX40 programs and late-stage development as well. And now turning to alopecia areata, we are on track and look forward to reporting data from the Phase IIb study in December of this year. A positive outcome here would reinforce the potential of RESPEG to provide a completely new treatment paradigm for patients with chronic dermatological diseases. The RESOLVE AA trial was initiated in March 2024. A total of 94 patients with severe to very severe alopecia areata who have not received the JAK inhibitor or other biologic, were randomized to two different dose regimens of RESPEC, 24 microgram per kilogram every two weeks and 18 microgram per kilogram every two weeks, or placebo. Patients were recruited across approximately 30 sites globally, with two-thirds of patients enrolled in Europe and the rest from North America. As a reminder, patient eligibility for this study was determined using the SALT score, both screening and randomization. Patients who experienced an unstable course of alopecia areata over the last six months per investigator assessment were excluded from the study, and patients with diffuse alopecia and other forms of alopecia were also excluded. The primary efficacy endpoint of this study will evaluate mean percent change in the severity of alopecia tool or SALT score at the end of the 36-week induction period. Secondary endpoints include proportion of patients achieving SALT20 which is an absolute SALT score of less than or equal to 20, mean percent improvement in SALT score at other assessed time points, and proportion of participants with greater than or equal to 50% reduction in SALT score at week 36 and other assessed time points. Importantly, SALT 20, the responder analysis, is also the established regulatory endpoint for Phase III trials. As Howard mentioned, the only available systemic therapies that are FDA approved for the treatment of alopecia areata are JAK inhibitors, which contain a number of black box warnings, and many patients experience hair loss after treatment cessation. With the limited treatment options available in alopecia areata, we believe there's opportunity for a novel mechanism like RESPEC, especially when the therapeutic is shown to be safe and well-tolerated. When comparing the outcomes from Resolve AA to the approved JAKs, we see low-dose solumiant as the appropriate benchmark. In its two Phase III trials, the approved 2-mig dose of solumiant showed that 15% to 16% of patients achieved SALT20 on the placebo-adjusted basis at week 36, and the mean improvement in SALT scores from baseline was 24% to 26% on a placebo-adjusted basis. Note that the placebo response rate in these trials is relatively low at 3% to 5% for the SOLVE20 endpoint and 4% to 9% on the mean reduction endpoint. Because of our differentiated mechanism of action compared to the JAK inhibitors and our safety profile, we see a very clear market opportunity for RESPEG and alopecia areata if RESPEG achieves these benchmarks. We look forward to sharing the top-line data from the 36-week treatment period of the RESOLVE-AA study in December and defining the potential for RESPEC in this new indication. Similar to atopic dermatitis, with positive results from Phase 2b, we would move very quickly into Phase 3 preparations, taking advantage of our fast-track designation in the alopecia areata indication. A quick few words on type 1 diabetes another autoimmune disease where RESPEC has great potential as a T regulatory mechanism. We believe RESPEC can potentially slow the progressive loss of insulin-producing beta cells, which are the target of the patient's overactive immune cells in this disease. As Howard mentioned, TrialNet has initiated and is funding an investigator-sponsored Phase II clinical trial evaluating RESPEC in 66 patients with new-onset type 1 diabetes. Lastly, On our pipeline progression, NECTAR-0165, our TNFR2 agonist, remains on track. This molecule has very high specificity for signaling through TNFR2 on Tregs to enhance and optimize their ability to regulate the immune system. NECTAR-0165 has also shown that a strong signal can be generated through a single-arm monobalance antibody, making it a perfect candidate for inclusion in bispecific and trispecific constructs. is to advance one of these antibody programs into the clinic next year. We look forward to sharing more on these sophisticated antibody engineering programs in future earnings calls. And I'll now turn it over to Sandy for the financials. Sandy?
[Name Not Disclosed]: Thank you, Jay-Z, and good afternoon, everyone. On today's call, I'll briefly review our quarterly financials and share updates to our financial guidance for 2025. We ended the third quarter of 2025 with $270.2 million in cash and investments and with no debt on our balance sheet. As discussed in our Q2 earnings call, this end of third quarter cash balance includes the completion of the secondary public offering in July with net proceeds of approximately $107 million. It also includes additional net proceeds of $34.3 million we raised in September from our existing ATM facility. We now expect to end the year with approximately $240 million in cash and investments, up from our prior guidance of 100 to 185 million. This increased year-end guidance also includes $38.3 million of net proceeds from additional sales of our ATM facility in October. Based upon our higher year-end cash balance, we are extending our cash runway guidance into the second quarter of 2027. Now turning to the income statement. Our non-cash royalty revenue was $11.5 million for the third quarter of 2025. We still expect our non-cash royalty revenue to total approximately $40 million for the full year. Our R&D expense was $27.3 million for the third quarter of 2025, and we still anticipate full-year R&D expense to range between $125 and $130 million, including approximately $5 to $10 million of non-cash depreciation and stock-based compensation expense. Our G&A expense was $16.1 million for the third quarter. We still expect G&A for the full year of 2025 to be between 70 and 75 million, including approximately 5 to 10 million of non-cash depreciation and stock-based compensation expense. Non-cash interest expense for the third quarter was $6 million, and we still expect non-cash interest expense for the full year to total approximately $20 million. Our non-cash loss from equity method investment was half a million dollars in the third quarter of 2025, and we still expect non-cash loss of approximately $10 million for the full year 2025. As an equity investor in Gannett Biochem, we have no commitment to contribute cash to Gannett. Our net loss for the third quarter was $35.5 million, or $1.87, basic and diluted net loss per share. And as I stated earlier, we now expect to end the year with approximately $240 million in cash and investments, with our cash runway extending into the second quarter of 2027. Finally, as we head into our December data reporting, we intend to enter into a quiet period for the month of December until we report the top line results for the RESPEG alopecia study. And with that, we'll now open the call for questions. Operator?
Operator: Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. In the interest of time, we do ask that you please limit yourself to one question at this time. Please stand by while we compile the Q&A roster. And our first question will come from Yasmeen Rahimi from Piper Sandler. Your line is now open.
Dominic: Hi, congrats on a great quarter. This is Dominic on for Yasmeen Rahimi. We just had a quick question on the upcoming AACAA data that will be presented. Could you help us understand what you hope to report in the presentation in patients with AD and asthma? And then moving forward, how would you expect this data to, I guess, impact development in asthma?
Crystal [Last Name Not Disclosed]: Thank you.
Howard Robin: Well, let me, I'll have Jay Z answer that, but I would tell you that at this point, we're not pursuing an asthma indication. I think, however, I think it's important to recognize that in ectopic dermatitis, the fact that we have an important drug that potentially solves that comorbidity issue is very exciting. And as I said earlier, 25% of the patients who have ectopic dermatitis also have asthma as a comorbidity. So I think it's a very important component of differentiating RESPEG, although we don't have a plan to run an asthma study. Jay-Z, would you like to help with the rest of the question? Sure, yeah.
Jay Z: Thanks for the question, Dominic. So at the ACAI presentation, we're presenting the results of a pre-planned exploratory analysis that was included in the study. There's a validated questionnaire instrument that's like a patient-reported outcomes It's ACQ5, which stands for that asthma control questionnaire. And with that, you can assess the comorbidity symptoms of asthma in patients that have both atopic dermatitis as well as asthma. And that allows you to look at the total sort of improvement in the ACQ5 scores over time. But it also lets you isolate on patients that have more severe, for example, uncontrolled asthma at baseline. And that's a subset of people that have higher scores on ACQ5 at baseline. For us, this is really interesting because, like we discussed, roughly 25% of patients have that, so roughly 100 people in our study also had asthma in addition to atopic dermatitis. And this allows us to assess the effect of RESPEG on asthma control and even potentially the improvements of those asthma symptoms in patients that also had atopic dermatitis. So one of the things that's so important about that is that when you are faced with treatment decisions as a physician and you know you have patients with atopy, and atopy constantly includes other organs, that's why such a high proportion of atopic dermatitis patients also have asthma, that starts to influence some of the treatment decisions. Right now, DUPI is really the drug that's gone to for people with comorbidity as DUPI has demonstrated activity in both asthma and atopic dermatitis and in patients that express both symptoms as well as each indication separately. And that's really likely with the IL-4 component of its mechanism. But the other agents in the class approved atopic dermatitis don't have nearly the level of effect that DUPI does. So this is a differentiating element of the Treg mechanism of RESPEC. And we do think differentiates RESPEC further from the other molecules in the class and the other molecules in development, as well as the approved agents like Xyle-13 selective antagonists and the OX40 classes as well. And we think it's something that is, you know, potential to really further build upon with RESPEC and something that we'll be, you know, exploring and thinking a lot about in the future. both in the setting of the comorbidity and, as Howard said, even beyond. Thanks, Tony. Thank you.
Operator: Thank you. Our next question will come from Julian Harrison from BTIG. Your line is open.
Julian Harrison: Hi. Thank you for taking the questions, and congrats on all the recent progress. It looks like you've had a few months now to socialize with the medical community, the initial Resolve AD results and Respex potential here. I'm wondering if you have a good sense now for the level of interest for a therapy that potentially has a truly remittive effect. To what extent do you think that could emerge as a differentiator for RESPEG in atopic derm? And then switching to alopecia areata, Jay-Z, I heard your comments around the lumient low-dose magnitude of valoxy potentially setting the bar. Do you see maybe an opportunity for
Howard Robin: you know use if efficacy is even lower than that just given how presumably safe respeg is uh potentially free of box warnings compared to jack inhibitors oh julian i'll take the first part of the question um look clearly um this mechanism the t-reg mechanism has received a lot of attention especially uh in in the nobel prize in physiology or medicine and uh i think given this very strong data we have in ectopic dermatitis, and the rescue data, or the escape arm data, I should say, where patients who failed to see any response on placebo did exceptionally well when they were crossed over to drug, I think that's incredibly compelling data, and we're very proud of that. The combination of that data with what we now see in the comorbidity of asthma I think sets apart RESPEG from a number of different drugs in treating ectopic dermatitis. So, yes, to answer your question more directly, there's a lot of interest in it. There's a lot of inbound interest in it, and I think it's going to have very good prospects. I'll let Jay-Z handle the rest of the question.
Jay Z: Yeah, thanks, Howard and Julie. And so, you know, I mean, in the context of the benchmarks, I think what's really important is that RESPEG has the potential to be a truly differentiated mechanism in alopecia areata by numerous factors. And one of those is especially given its safety profile. Right now, there are no approved biologics in the alopecia areata space. And there's really been no therapy that's demonstrated a sustained treatment effect. And what I mean by that is even a short-term interruption in a JAK course can cause hair thinning. It's really quick to wear off. And so you have the ability to address so many features that both affect the disease and then the convenience factor for the patient and substantially the comfort level for the physician in a drug that doesn't have a black box warning, which is one of the issues and limitations of the JAK inhibitors. There's no question that those are great drugs for reducing inflammation and reducing inflammation quickly. They're just very difficult drugs to take for a long period of time. And these are chronic conditions. So it's really the challenge with a drug like that. But with ResPag, you can turn that whole problem, you know, on its side. And we have done a lot of market research. We've tested the profile. And the profile of low-dose Illumiant, you know, we find is very competitive given all of the other elements, features of the mechanism of action and the differentiated safety profile. We know that there's space there, to your point, Julian. But we're using that as a reasonable kind of proxy benchmark for now. It is an approved drug and an approved dose, but there is some space around that, to your point.
Julian Harrison: Thanks. Excellent. Thank you. That's all very helpful.
Operator: Thank you. Our next question will come from Jay Olson from Opco. Your line is open.
John Eliza: Oh, hi, this is John Eliza J. Thanks for taking the question and congrats on the progress. Maybe speaking to the AA, I'm just wondering how fast you can maybe start the phase three program and are you planning to, you know, move the program by yourself or in a partnership if the December data is positive? And separately, I'm also wondering, in the phase three AD study, are there any patients have LOPG-Ariana comorbidities and if so, Thank you.
Howard Robin: Well, I think the first part of your question, I didn't hear it all clearly, but I think the first part of your question, I'll let Jay-Z take the second part. The first part was, when do we think we could start a study in alopecia areata? I think, you know, depending on the data that we receive in December, we certainly would look forward to starting it next year. I think it's important because, as we talked about, The only current therapy is a JAK inhibitor, and they come with lots of concerns and warnings. And as I did describe, at a physician surveys that we've conducted, physicians are somewhat reluctant to use a JAK inhibitor to treat alopecia areata given the safety concerns. So I think if we have a new modality to treat such a very serious disease, in a condition that causes extreme depression in people, I think it could be very, very important. And consequently, we do plan to start that study next year. I'll let Jay-Z comment on the rest.
Jay Z: Yeah, thanks, John. So we did look at multiple comorbidities in the atopic dermatitis phase 2b study. Asthma was by far the largest patient population, as I mentioned. Roughly 100 people had both atopic dermatitis and asthma in that study. And they'll be presented at ACAAI this weekend. In terms of alopecia, we'll also look at vitiligo, for example, very, very few people. So really not a large enough patient population to isolate out as a subgroup, like a handful, a few people in alopecia that had both of the diseases. Obviously, our phase 2B results in alopecia, which read out next month, that is by far a more definitive data set, right? Much, much larger sample size. Obviously, a patient population enrolled with that is their primary disease. And then, of course, we'll be looking at the treatment effect in that patient population reported next month.
John Eliza: Thanks. Thank you.
Operator: Thank you. Our next question comes from Cha Cha Yang from Jefferies. Your line is open.
Cha Cha: Hi, this is Cha Cha on for Roger Song. I was wondering, in addition to low-dose aluminum, are there any therapeutics that are in development biologics for alopecia that you think would be an appropriate benchmark? And then my second question is, are there any IL-2 specific studies that you think could provide read-through to RESPEC in alopecia?
Crystal [Last Name Not Disclosed]: Thanks. Jay-Z, you want to cover that? Yeah, hi, please. Sure. Hey, Tasha.
Jay Z: Yeah, so, yeah, there are, you know, a couple of biologics in development for alopecia. And we discussed them. There's like an IL-7 receptor and other kinds of agents. So, you know, I think that there are some earlier data sets. Our goal is we're doing a much, much larger study than those earlier programs. Um, as we described, you know, 94 people were enrolled in randomized in the phase two B alopecia study that we're doing. We also have multiple doses. Um, so a much larger study that gives a chance to really assess the treatment effect, which I think is going to be more informative than a lot of the single arm or much, much smaller studies that have been done to date. Um, but it's certainly, you know, an area that people are exploring Tregs remain a very important mechanism. you know, that is invoked from a lot of translational studies in patients with alopecia areata. We know that there are low levels and deficiencies in Treg function, and we also know Tregs are necessary for hair growth and for hair moving through the hair growth cycle. And the actual antigen phase that actually is associated with the elongation of the hair once it attaches down at the root actually requires Treg signaling to the stem cell compartment. So we know that those are multiple key mechanisms, and those are one of the big reasons why we're so excited in conducting the study that we'll be reading out the top-line data for next month. And then in terms of IL-2-specific studies, there have only been a few studies that have been published with IL-2. One was a case study, and one was a small randomized study. The main situation is low-dose IL-2 is really not a good proxy for RESPEC. You know, with RESPEC, we induce such a higher amount of Tregs, much, much higher than low-dose IL-2 can ever achieve, a much greater duration of Treg elevation from a given dose, and the ability to treat for a very long time. You know, we've now treated patients for over a year, for example, for, you know, a 52-week period in the Phase 2b study in atopic dermatitis patients. So it's definitely a surrogate in the sense of a Treg elevating agent, but really RASPAC substantially exceeds anything that low-dose IL-2 has been able to present across multiple indications. Thanks.
Crystal [Last Name Not Disclosed]: Thanks so much for the call. That's super helpful.
Operator: Thank you. Our next question will come from Mayank Montani from B. Reilly Securities. Your line is open.
Mayank Montani: Yes, good afternoon. Thanks for taking our questions and congrats on a productive quarter. On the alopecia top line data analysis, would you have any off-treatment responder rate you plan to report on given some patients may have been past that 36-week treatment period? And if you could remind us if there's an escape arm option here. for the placebo non-responders to cross over. Obviously, you know, wonder from your ATD experience, the peak efficacy, you know, from the EADB data, you didn't get until, you know, 24, 48, 44 weeks even. So just wonder what's your plan to assess, you know, if efficacy increases beyond that 36-week period, what's the kind of plan there? And then I have a quick follow-up.
Jay Z: Sure, yeah. So firstly, in, you know, the kind of information, you know, that we would present at the NET in December. We'll be presenting data from the 36-week induction period, you know, in the study. The primary endpoint is the mean percent reduction in SALT score from baseline. And then the key secondary endpoints that are really, really meaningful is the proportion of people that achieve the SALT 20 and also the SALT 10. And SALT 20 is the registration endpoint in the U.S. and SALT 10 in Europe. And then I mentioned, you know, earlier in the presentation, also the additional secondary endpoints, some of the time-dependent endpoints, some of the proportional increases in the kind of hair regrowth, right, as metrics. And then the other things that kind of round out, the baseline demographics, you know, the safety profile, all the other things. But importantly, Mike, right, the study is still going to be ongoing. So as you know, the way we designed the study is – People that reach week 36 that are experiencing benefits, such as hair regrowth, for example, but that have not yet reached a SALT20 metric, they have the opportunity to take an additional 16 weeks of treatment to 52 weeks for a full year. So there's a proportion of people that will be ongoing. And also, the study design has a 24-week off-drug observation period. So whenever a patient completes treatment, whether that's at nine months or at 12 months, they're then followed for that additional 24-week period of time. And that's really designed to assess that if you grew hair, can you keep hair, right? Which is a significant differentiating element from a JAK mechanism of action where the hair loss is really, really rapid when the drug dosing is stopped. So because the study is still ongoing, you know, I mean, it's You know, we can't say yet the totality, but definitely the 36-week endpoint, which is the primary analysis, with the entire population crossing the 36-week is going to be the main subject of that top-line presentation.
Mayank Montani: Escape arm? Did we get an escape arm here?
Jay Z: Oh, no, there's no escape arm in the study.
Mayank Montani: Okay, thank you. And on the auto-injector development, you know, How far along are you, and is that going to be at the start of your phase three study, and is that kind of part of the protocol as you get into the end of phase two discussion? Thanks for taking my question.
Jay Z: Sure. Yeah, so the autoinjector development is ongoing, and our goal and plan is to have the autoinjector available at the time of launch of RESPEC. The phase three studies will be conducted in the same way the phase two studies were, where the drug would be used in a vial. And for us, you know, we maintain that really for speed because this allows us to start the phase three studies as quickly as possible relative to when we presented the top line data in June of this year. And then in terms of your other question, you know, just contextually, you know, at the end of phase two meeting, you really discuss everything in the plan to your BLA. So that includes not just the phase three clinical development program, the registrational and pivotal studies, you know, it also includes the CMC. So yes, you know, we have, you know, presented our plans for the final presentation of the product, the auto injector, and then all the work that we do during the phase three studies into the BLA to have that available for launch.
Operator: Thank you. Our next question will come from Arthur He from H.C. Wainwright. Your line is now open.
Arthur He: Hey, good afternoon, Howard and team. Sorry, I apologize if the question has been asked before. So given the coming for the alopecia, Jay-Z, maybe could you tell us a little bit more, like, what the potential RASPAC can offer compared to the JAK inhibitor here for the alopecia patient?
Jay Z: Yeah, this is a great question. I mean, I think that one of the situations with the JAK inhibitors, and we touched a little bit on this earlier, is that they definitely are effective at reducing inflammation. Like if you have common gamma chain uses of multiple cytokines, use any either homo or hetero dimers of JAKs. And it's an important part of the signaling cascade in response to multiple cytokines. And they're well known as effective ways of lowering inflammation quite quickly. But the challenge with using a JAK inhibitor in any indication where it's approved is that long-term use carries with it some disadvantages, right? So the drugs have black box warnings. They have other significant limitations. They require monitoring. There's just a number of things that make them a little bit more delicate to use. And in the dermatological setting, some of those things are a little bit undesirable. One of the things that RASPAC can offer is if the efficacy profile, as we discussed, reaches a benchmark such as a low-dose JAK in, say, the aluminum setting, it already brings with it a completely different you know, risk profile, right? It would not have a black box warning. It would have a completely different and much, much better safety profile and really has a safety profile that's much more aligned with being a very long-term chronic used drug. Also, the potential of being the first biologic in this space gives it a real tremendous advantage because that starts to really open access because we've learned from multiple studies that physicians are They're not so necessarily excited to try JAKs as a first option for patients with the disease. So having another alternative that's available could take a significant, you know, an opportunity advantage. And then the last one is really comes down to that potential of maintenance. So JAK inhibitors really lose their effect very quickly. And it can be very psychologically difficult for patients because if you spend weeks and months regrowing hair that you didn't have in a really long time, and then any need to interrupt the jack, whether it's a safety signal or other reason or liver enzyme elevation or something, then that can lead to loss of all that hair that you've grown, which can further drive the depression cycle that's a component of this disease. With Respec, there's the potential of maintaining the hair that was grown having interruptions in drug dosing, that would be a problem. And that would be completely transformational. So these are all things that we think contribute to a very substantial opportunity for ResPag and LLP-Sheriotta.
Arthur He: Thanks, Jay-Z. So another question is, given the new Pedicin data, how should we think about the primary endpoint for the approval in the future? Do you think the SALT20 still could do the job, or we probably should look into the SALT10 or even SALT0 there for the future drug for the other patient?
Jay Z: Yeah, well, I mean, the health authorities set the registrational endpoints, right? And so right now those are defined, right, as SALT20 in the U.S. and SALT10 in Europe. But obviously, every study measures multiple secondaries, right, including, you know, eyelash, including salt zero and so on. So I think that, you know, we leave that in the hands of the regulators. In terms of OOPA's efficacy, I mean, it's, I think everywhere that there are multiple JAK inhibitors approved, OOPA or RINVOTE seems to always win, right? It just consistently produces the greatest amount of efficacy compared when it goes head to head against other agents. And I think we've seen that in multiple indications, Arthur, right? Not just in this one. It does carry with it a little bit more of a safety profile, which is related, right? It's more on target and more on target talks in addition to other things. But I do think as compared to the other JAK inhibitors, that OOPA is going to be very important. Probably take a a significant position against the other JAK inhibitors, but we don't really see that as impacting the biologic, right? Again, there are numerous indications where biologics and small molecules, JAKs and non-JAKs coexist. Atopic dermatitis is a great example. In psoriasis, you have TIK2 mechanism coexisting and others. And there's really a large enough patient share and the need for multiple mechanisms, that always makes plenty of room for multiple mechanisms in this indication.
Arthur He: All right. Thanks very much for taking my question.
Operator: Thank you. And we do have time for one last question. And our last question will come from Andy Shea from William Blair. Your line is open.
Andy Shea: Great. Thanks for taking our questions. Mary, it's great to have you back. uh my we have two questions so for the resolved ad study i believe you spent a lot of time and resources to ensure that the placebo rate is low so so having gotten a chance to review that initiative so that you can be best positioned for the positive phase three outcome and then the second question uh maybe for howard what's your current manufacturing footprint I figured given the intense interest in RESPEG, it would be really nice if you can secure one of those national priority vouchers.
Crystal [Last Name Not Disclosed]: Thank you.
Howard Robin: I'll take the second part first, and Mary can continue. Look, we are looking at a number of different options there. You know, we sold our PEGylation manufacturing facility to Gannett Biochem, but we have a priority position there, and we certainly have you know, a guaranteed source of those raw materials. And we have a number of different contract manufacturing companies, very well-known companies that we work with. So I'm not concerned about, at this point, the ability to successfully manufacture RESPEG. And we are looking at the vouchers, et cetera. I will let Mary talk to you about the other part of your question.
Mary [Last Name Not Disclosed]: Thanks, Howard, and really great to hear your voice too, Andy, and I'm really happy to be back. I mean, as you said, the data from Resolve AD are very exciting, and I've also had the opportunity to speak to multiple dermatologists since I've been back who are also very excited about the totality of the data, the speed of onset, and the excellent safety profile. So it's very exciting to move this forward. And certainly in our phase three program, we have every plan to implement the exact same procedures that we did to minimize the placebo effect. And some of those are, of course, ensuring that we have board certified dermatologists participating in our clinical trials. We also make sure that the eligibility criteria is met both in the screening and right before patients are randomized, and so we took multiple actions. Also, you know, in our Phase IIb, we had a quite large size of our placebo group, and we will, of course, have the same when we proceed forward in a larger group. phase three study. So we were very pleased that we were able to implement multiple different procedures and activities in order to ensure our placebo effect was very low, and we believe we will continue to be very successful in our phase three as well. So we look forward to moving forward. We've been doing a lot of planning. We're going to have our end of phase two meeting with the FDA by the end of this year, and so we'll have a clear path forward to a BLA. Great.
Operator: Good luck with that. Thanks.
Mary [Last Name Not Disclosed]: Thank you.
Operator: Thank you. And this does conclude our question and answer session for today's conference. I'd like to turn the call back over to Howard Robin for any closing remarks.
Howard Robin: Well, thank you, Crystal, and thank you, everyone, for joining us today. We greatly appreciate your continued support. And I want to thank all of the patients and their caregivers that have trusted and continued to trust Nectar to treat their disease. None of this research would be possible without them. And I also want to thank our employees for their dedication and extremely hard work And we look forward to delivering data from our RESPEC program data in alopecia areata in December and additional results from the program in ectopic dermatitis in the first quarter of next year. So please stay tuned. Thanks for joining us.
Operator: This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.
