Hello and thank you for standing by. Welcome to the Nectar Therapeutics third quarter 2026 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. Please be advised that today's conference call is being recorded. I would now like to hand the conference over to Vivian Wu from Nectar Investor Relations to kick things off. Please go ahead.

Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. On today's call, you will hear from Howard Robin, our President and Chief Executive Officer, Dr. Mary Tagliaferri, our Chief Medical Officer, Dr. Jonathan Zalevsky, our Chief Research and Development Officer, and Linda Rubinstein, our Chief Financial Officer. Before we begin, I would like to remind you that we will be making forward-looking statements regarding our business, including statements related to therapeutic and commercial potential, and Development Plans for Respec Albus Lucan, the timing and execution of clinical trials, expectations for clinical data and regulatory filings, potential strategic partnering activities, financial guidance and other statements regarding the future of our business. Because forward-looking statements relate to the future, they are subject to uncertainties and risks that are difficult to predict, many of which are outside of our control. For a discussion of these risks and uncertainties, please refer to our filings with the SEC, including our most recent Form 10-K and subsequent filings. We undertake no obligation to update these forward-looking statements, except as required by law. A live webcast and replay of this call will be available on the investor relations section of our website at Nectar.com. With that, I'll turn the call over to Howard.

Thank you, Vivian. Thank you to everyone for joining us this afternoon. Q3 was a transformative quarter for Nectar as we advanced ResPag into Phase III studies. And building on its compelling Phase II results across two key immune derm indications, we initiated a comprehensive Phase III plan for ResPag in both ectopic dermatitis and alopecia areata. Our global Phase III studies in ectopic dermatitis have started, and our Phase III study in alopecia areata is on track to start in December Thank you for joining us. In spite of a number of approved systemic therapies to treat patients with moderate to severe ectopic dermatitis, only one in four patients today receive a systemic treatment. Ectopic dermatitis is a highly heterogeneous disease, meaning the biology driving the underlying disease state can be complex and can vary significantly from one patient to another. The current approved biologics target one single inflammatory pathway. specifically the type 2 inflammatory pathway and mostly to IL-13 cytokine blocking. In order to ensure we have treatments that can address the needs of all patients with ectopic rheumatitis, it is necessary to have novel mechanisms that target the heterogeneous nature of this disease. Importantly, today we know that at least half of patients on an existing biologic report inadequate control of their ectopic dermatitis for this reason. To that end, Respec's novel Treg mechanism offers a critically important therapeutic modality for patients and one that is currently missing from the treatment armamentarium. We know from our market research that physicians are looking for different mechanisms of action than those that are already approved. Rather than blocking a single downstream inflammatory pathway, Respeg's first-in-class Treg approach selectively expands the immune cells to restore immune balance. In other words, we're addressing the underlying inflammatory drivers rather than simply controlling the symptoms of the disease. Jay-Z will talk more about some of the important translational work we have from Respeg AD, which demonstrates the unique profile we have for Respeg. In the commercial landscape in ectopic dermatitis, We've already seen clear evidence of the demand for a mechanism outside of IL-13. Nemluvio, which is an IL-31 cytokine blocker, gained a label in ectopic dermatitis only in combination with topicals. And based on recent US claims data, Nemluvio is capturing at least 10% of new treatment starts about seven quarters into launch. In fact, since its launch, Depixent has lost these new-to-brand patients starts going from an 81% share of starts in 2024 to 65% today, with more than half of the share that Depixent has lost going to novel MOAs. Physician willingness to start patients on a novel agent outside of Depixent reaffirms for us the market research we've conducted for ResBag, indicating an opportunity for ResBag in first-line as well as second line treatments. With the recent setbacks in the OX40 class, we believe there are no agents in mid to late stage development that address the underlying heterogeneity of disease and ectopic dermatitis in the way that RESPEG addresses it by targeting the full range of inflammatory pathways. This gives RESPEG a truly unique competitive position. In our research, Approximately 90% of surveyed dermatologists indicated that they would consider starting a patient on ResBag before starting a patient on another biologic or a JAK inhibitor. This underscores the dermatologist community's receptiveness to try novel MOAs as a first-line treatment. With regulatory agency alignment, we're advancing our Phase III program to support a broad label including first-line use in patients new to biologics and JAK inhibitors as well as second-line use in previously treated patients. In alopecia areata, Respec has a unique opportunity to offer a compelling first-line therapy as compared to the existing approved JAK inhibitor class. Oral JAK inhibitors require daily dosing and carry box safety warnings and laboratory monitoring requirements. The market, according to Decision Research Group, is forecasted to reach approximately $5.2 billion by 2033. And Mary will talk more about our phase three programs in ectopic dermatitis and alopecia areata in a few moments. And at the recent EADV conference, we presented multiple oral presentations for RESPEC, which Mary will also review in a bit. Beyond our two lead dermatology indications, We believe RESPEG continues to offer broad potential in other autoimmune indications. The phase two study in new onset type one diabetes sponsored and funded by TrialNet is ongoing. We currently estimate that we could have data from the first cohort of patients in late 2027. And as I said last quarter, we're planning to initiate a new signal seeking trial for RESPEG in another immune indication, and Mary will talk more about our specific plans and that opportunity. And with that, I'll turn the call over to Mary.

Thank you, Howard, and good afternoon, everyone. As stated earlier, we had a significant presence at the EADV conference with three separate oral sessions for RESPEC. We had two presentations for Resolve AD, One was a very important translational biomarker sub-study conducted at Mount Sinai, and the second was our 52-week monthly and quarterly maintenance dosing data. For alopecia areata, we presented off-treatment data demonstrating strong retention of hair regrowth and additional hair regrowth for patients who received 52 weeks of RESPEG treatment and were followed for six months off treatment. On the heels of this strong EADV presence for RESPEG, We are enrolling patients into our Phase 3 Zenith-AD program. Our global Phase 3 Zenith-AD program includes three pivotal studies with 510 patients 12 years or older in each study. All three of these studies have been initiated. The first Zenith-AD1 study is evaluating RESPEG monotherapy in patients who are oral JAK inhibitor and biologic naive. For ZNF-AD2, we've recently made a change to adapt this study to evaluate RESPEG in combination with topical corticosteroids and enroll both naive and experienced patients. This change incorporates recent input from regulatory authorities and is intended to support a label for RESPEG that extends beyond monotherapy to combination use with topical corticosteroids. is enrolling patients who are JAK inhibitor and biologic experience. With these three studies enrolling a total of approximately 1,500 patients, we now have a registrational program designed to support the broadest possible label for RESTAG at commercial launch, spanning adults and adolescents, biologic and JAK inhibitor naive and experienced patients, and monotherapy treatment as well as combination use with topical corticosteroids. The program positions RESPEG for usage across the full spectrum of patients with moderate to severe atopic dermatitis. As Howard stated, we still expect our initial top-line data in the summer of 2028 from the Zenith AD studies with a goal of filing a BLA by the end of 2029. All three Zenith AD studies include a 24-week induction period, with patients receiving RESPEG at 24 micrograms per kilogram every two weeks or placebo. The primary registrational endpoint is an investigator's global assessment or IGA at week 24. EZ-75 is a key secondary registrational endpoint and will also serve as a co-primary endpoint with IGA in significant territories outside the United States. Other important endpoints, which are multiplicity protected in the trials, include itch and patient-reported outcomes, as well as control of comorbid asthma, which affects approximately 25% of patients with moderate to severe AD. After 24 weeks, patients who achieve an EZ75 or IgA0 or 1 response will enter a 28-week maintenance period, evaluating less frequent monthly and quarterly dosing. During induction in the Phase IIb RESOLVE-AD trial, RESPEG demonstrated a rapid onset of activity with early improvements in skin clearance and itch and strong efficacy across key clinical endpoints. The longer-term results that were presented again at EADV provided further evidence of RESPEG's potential to deliver durable and deepening disease control. Importantly, both monthly and quarterly maintenance dosing demonstrated sustained responses across key measures of disease activity, including easy responses, clear or almost clear skin as measured by VIGA, and clinically meaningful itch relief. We also saw new responses emerge in patients who had not achieved these thresholds during induction, with more patients reaching complete skin clearance over time. As Howard mentioned, we will report the 52-week off-treatment follow-up data from Resolve AD in the first quarter of 2027. As a reminder, we ran an induction treatment and a maintenance treatment in Resolve AD. You'll recall that patients who completed the maintenance treatment on Resolve had high durability of responses and continuing deepening of responses for endpoints like EZ75, EZ90, and EZ100. Patients who completed the maintenance treatment of 52 weeks entered an off-treatment follow-up period where we continued to evaluate the maintenance of their responses. For these patients who completed 52 weeks on treatment and entered the off-treatment evaluation period, we assessed their maintenance of disease clearance, including easy and other metrics of disease that our patient reported, such as itch and quality of life. After completion of the 52-week on-treatment maintenance portion of the trial, follow-up off-treatment assessments were done at weeks 4, 13, 26, 39, and 52. A total of 125 patients in Resolve AD completed the maintenance treatment period. Of those, 110 patients were in the RESPEG maintenance treatment arm and 15 were in placebo. The placebo patients were included in the off-treatment period to continue to maintain the blind for patients in the study. Of note, there was no option for additional treatment or enrollment into a long-term extension study following the 52-week off-treatment period. This differs from all the placebo withdrawal studies for the currently approved agents. In Resolve AD, Patients received no injections during the off-treatment period, unlike placebo withdrawal designs that continue a sham injection. To our knowledge, only one other trial has included an off-treatment follow-up that was not a placebo withdrawal design. This is the Phase II ROCA OX40 study. Their on-treatment period was only 36 weeks. and their follow-up off-treatment period was only 20 weeks without sham placebo injection. So, what sort of bar are we looking for here? As we've done when we reported our maintenance data, we like to look at Dupixent as a good comparison. When you look at Dupixent, they completed a nine-month follow-up off-treatment analysis looking at maintenance of the EZ75 response. Now, this study was a placebo withdrawal design, but they reported that approximately 50% of the patients maintained their EZ75 at nine months off treatment. If we see this level of maintenance of EZ75 at 12 months off treatment or better, that would be an interesting finding. Why? Because it opens up the possibility to move EZ75 responders to quarterly dosing after 52 weeks of induction and maintenance treatments. Additionally, as further differentiation, such results could create the potential for patients achieving a deep and sustained response across multiple disease measures to transition to dosing as infrequently as every six months following 52 weeks of induction and maintenance therapy. Now turning to alopecia areata. We recently presented new off-treatment results for the first time at EADV that provide further evidence of RESPEG's mechanistic potential to deliver durable and deepening responses. In April, we presented data that showed treatment with RESPEG through Week 52 resulted in higher SALT20 responses. At EADV, we showed that these patients sustained their responses for months after their treatment ended. This is especially important in alopecia areata, where loss of hair regrowth following discontinuation of a JAK inhibitor is a major concern for both patients and physicians alike. This durability of response supports evaluating less frequent maintenance dosing after one year of twice-monthly RESPEG treatment for patients who achieve SALT20 or better. For example, 7% of patients who were treated for 52 weeks achieved a SALT10 at the end of treatment, and six months later off RESPEG, 19% of patients had achieved a SALT10. These data demonstrate real promise for patients. Importantly, we have now shown multiple times that treatment with RESPEG demonstrated durable responses across atopic dermatitis and alopecia areata. Together, this reinforces RESPEG's potential to deliver sustained disease control with infrequent dosing, a potentially important differentiator in the treatment of chronic inflammatory diseases. Our Phase 3 Zenith AA study will start next month. This single global registrational study will enroll approximately 850 patients, ages 12 and up, with severe to very severe alopecia areata. Patients will receive RESPEG at 24 micrograms per kilogram every two weeks or placebo through week 52. The primary endpoint will be salt 20 or less at week 52. The study will include both patients who are naive to systemic treatment and patients who have previously received the systemic agent after an appropriate washout. It will also enroll patients with a current alopecia areata episode of up to eight years. following 52 weeks of treatment, patients will enter a long-term extension. Those patients who achieve a good response during the 52 weeks of treatment will receive monthly or quarterly maintenance dosing. We currently expect data from Zenith AA in 2029. With Zenith AA, the overall Zenith program will enroll approximately 2,400 patients 12 years and older across the atopic dermatitis and alopecia areata studies enabling a substantial safety database to support registrational approval. Separately, we are also planning an investigator-sponsored study that will be conducted at Mount Sinai in patients with alopecia areata which will include moderate alopecia areata patients as well as severe and very severe patients. The population of moderate patients is a large opportunity and we believe generating data in this patient population is critical as we think of the overall positioning of RESPEG across the entire alopecia areata patient population. This IST will start in the first half of next year. As Howard mentioned, we are also planning to explore new indications with RESPEG. The first study we are planning is a proof of concept study in about 30 patients with vitiligo. Vitiligo represents a compelling potential expansion opportunity for RESPEG with a significant unmet need, a large under-penetrated market, and strong mechanistic rationale for Treg-based therapy. Today, there are approximately 1.9 million Americans with Vitiligo, yet only 15% seek treatment. Similar to the competitive landscape in alopecia areata, the only approved agents, for those in late stage development are JAK inhibitors. All these agents, whether oral or topical, come with significant safety concerns and lab monitoring burden. Moreover, most patients lose near complete repigmentation within a year of stopping treatment with JAK inhibitors, presenting an unmet need for differentiated treatment options that can lead to durable responses and less frequent doses. Importantly, Fidoligo biology provides a strong rationale for RESPEC. Fidoligo is an autoimmune derm disease in which cytotoxic CD8-positive T cells attack and destroy melanocytes. This phenomenon results in impaired Tregs characterized by loss of IL-10 and TGF-beta-1 regulation, which results in loss of pigmentation. In a minute, Jaycee will talk more about the biomarker substudy from RESOLVE-AD that was presented at EADB. Critical to vitiligo, that study showed that treatment with RESPEG led to serum IL-10 and TGF-beta-1 elevations as early as week 2, which were positively correlated with clinical effect at week 16. By restoring both Treg number and function in patients with vitiligo, RESPEG has the potential to generate meaningful clinical responses in this indication. This study, which will start in the next few months, will generate proof of concept data in late 2027 or early 2028. Building on this, we continue to explore additional indications where RESPEG's novel Treg approach has clinical application, including asthma, where Respec has already demonstrated strong reduction in ACQ5 scores in patients with atopic dermatitis and comorbid asthma. We look forward to sharing more as these programs develop. With that, I will turn the call over to Jay Z. Jay Z?

Thank you, Mary. I'd like to spend a few minutes talking about the biology of Respec and specifically the biomarker data we presented at EADV which provide important new insights into how RESPEG works and help us better understand the clinical responses we've observed. As Howard mentioned, atopic dermatitis is a complex heterogeneous disease involving multiple inflammatory pathways. However, the currently approved biologics target only one inflammatory pathway, specifically type two inflammatory pathway through IL-13 cytokine blockade. RESPEG on the other hand, is designed to selectively expand the immune cells to help restore balance across multiple pathways. And to better characterize this novel Treg mechanism, we worked with investigators at Mount Sinai to conduct a biomarker analysis in 100 patients from the RESOLVE-AD study. The sub-study analyzed gene and protein expression, blood samples, and non-invasive skin tape strips, comparing ResPak at the doses selected for phase three The results showed that as early as week two, there were significant increases in FOXP3 and IL-2-RA, two important markers of regulatory T-cell activity. And at the same time, we saw changes consistent with normalization across multiple inflammatory pathways involved in atopic dermatitis, including Th1, Th2, and Th17 inflammatory pathways, as well as JAK-STAT signaling. and these effects were evident in both the skin and circulation, providing further evidence of the breadth of RESPAG's mechanism. Importantly, we were also able to establish a relationship between these early molecular changes and the subsequent clinical improvements. Changes in several blood biomarkers at week two, including increases in IL-10 and TGF-beta-1 expression and reductions in the inflammatory marker TARC, were significantly correlated with greater improvement in EASY scores at week 16. These correlations were statistically significant in RESPECT-treated patients and were not observed in the placebo group. The RESPECT-treated patients in this sub-study also achieved a mean 64% reduction in EASY at week 16, consistent with the results in the broader study population. We also observed changes in the molecular signature associated with cardiovascular disease, atherosclerosis, and alopecia areata, strengthening our belief in RESPEG's potential as a pipeline and a product. These findings provide important validation of RESPEG's differentiated mechanism. They show that RESPEG induces early regulatory T-cell associated activity and influences a broad range of inflammatory pathways with molecular changes that are linked to later clinical improvement. Beyond RESPEG, we are continuing preclinical work for our TNFR2 program which includes Nectar 0166, our bispecific program that combines Nectar 0165, our TNFR2 agonist antibody with a second validated immune target that we have not yet disclosed. This program extends the same core strategy that underpins RESPEC, developing therapies that restore immune regulation rather than simply suppressing a single inflammatory signal. And with that, I will turn the call over to Linda to review our financial results. Linda?

Thank you, Daisy, and good afternoon, everyone. On today's call, I'll review our quarterly financials for the third quarter of 2026 and updates to our 2026 financial guidance. We ended the third quarter of 2026 with approximately $953 million in cash and investments with no debt on our balance sheet. We now expect to end 2026 with more than $840 million in cash and investments, which is at or above the top end of the range of $815 to $840 million provided on our Q2 call. Turning to the income statement, our third quarter 2026 non-cash royalty revenue totaled $8.5 million. We now expect non-cash royalty revenue will be approximately $38 million for the year. Our R&D expenses were approximately $44 million for the third quarter of 2026. We expect an increase in the fourth quarter due to RESPEG-AD enrollment, AA clinical startup, and supporting CMC activities. We now anticipate full-year R&D expense to range between $185 and $200 million, which includes approximately $5 to $10 million of non-cash depreciation and stock-based compensation expense. Our G&A expenses were approximately $25 million for the third quarter. We expect G&A expenses for the full year 2026 to be approximately $65 million which is within the range given previously. And this includes approximately $5 million of non-cash depreciation and stock-based compensation expense. Non-cash interest expense for the third quarter was approximately $6 million. We now expect non-cash interest expense will be approximately $28 million for the year. Our net loss for the third quarter was approximately $56 million, or $1.63 basic and diluted net loss per share. And as I stated earlier, we expect to end 2026 with more than $840 million in cash and investments. Our financial position is strong, enabling us to execute our robust and exciting RESPEC Zenith AD and Zenith AA program. And with that, I'll hand it over to the operator for questions.

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. We compile our Q&A roster. And our first question will come from Yasmeen Rahimi from Piper Sandler. Your line is open.

Good afternoon, team. Congrats to all of the updates and really excited to hear about your interest in vertiligo and moving forward, but would love to get a little bit more color on what work is needed to complete in order to kick off the studies in the upcoming months. Would you envision a placebo-controlled study, an open-label study, and also maybe give us some insight on how do you think about dose selection and vertiligo? Sorry, this was and more than one question. My apologies.

Hi, Izmin. That's a really good question. I will defer to Mary on going through some of the detail on that. I would say that it's an interesting indication because as Jay-Z did say, it's very much T-cell mediated, it's a T-cell mediated disease. So I think it's really a perfect opportunity for us to show the potential for RESPEG in a broad, you know, applications in autoimmune disease. So Mary, maybe you could answer some of the questions about study design.

Yes. Hi, Yasmeen. So this is a proof of concept study, you know, and we want to establish whether the strong biologic and mechanistic rationale we see for RESPEG in vitiligo that we've seen in our immune germ diseases translates into vitiligo. And as you know, probably, there are companies that have done an open label single arm study and then moved into a phase three program. And so we do feel that there's an opportunity to do this because like alopecia areata, There is a very low placebo effect on these endpoints like facial VASI 75 or even mean percent change from baseline and facial VASI. So we do believe that there is an opportunity to very efficiently conduct a trial in an open label population. We are still working on the final I just had a call this morning with Dr. David Rosemarin who we're working very closely with on this study design and we will be able to launch this study next year. So stay tuned as Howard and Jay Z and I have said, there's such strong mechanistic rationale for going into this indication. And also given that this is primarily a TH1 dominated disease and we saw the good data in alopecia areata, we believe that there's great read through into vitiligo from what we've already collected in these inflammatory skin diseases. and, you know, as we mentioned, this is really an under-penetrated market with only 15% of patients getting treated. So we're very excited to, you know, quickly move forward into this new indication. So thank you.

Thank you. And our next question will come from Julian Harrison from U.S. Bancorp, PTIG. Your line is open.

Hi, thank you for taking the questions. As we look ahead to the Resolve AD off-treatment data next quarter, can you walk us through the rationale for why D2 weeks instead of 36 weeks on treatment may set RESPEC up for better odds of sustained responses off-treatment? And then, are there any important differences in statistics versus the Phase 1b atopic dermatitis trial we should keep in mind? Can you also talk to us about how you'll be handling rescue therapy and missing data there?

Hi. So we're really excited to look at these data. We've given you some guidance that we had about 125 patients that had the dosing. I do believe that what we've learned from our maintenance period in the phase 2b was we saw one very robust maintenance of EZ75 and as you'll remember we follow patients who you know just received Q12 week dosing or once a quarter and those patients who came off of 16 weeks of Q2 weeks of 24 micrograms per kilogram half of them went on to receive just three doses of RESPEG and what we saw is, you know, 83% of those patients were able to maintain their EZ-75. So I think we have nice data from the Phase 2b, as you were mentioning, that show this durability with just, you know, three doses of Restag and we did even see patients having deepening of responses That, coupled with the data that we saw from alopecia areata, where we dose patients for 52 weeks and then stopped treatment and followed those patients who had SALT20 for an additional six months, we did also see really good durability with those patients. And so I would say the maintenance portion and the data that came out of the Phase 2b, coupled with what we saw from the Phase 2b and alopecia areata, both strongly support that we will be able to see patients having durability of treatment with 52 weeks off of RESPEG. And the next part of the study, you know, we're going to be able to look at, well, what happened to patients, you know, for 13, 26, 39, and 52 weeks off treatment? We believe that this will help guide, you know, in particular after 52 weeks, What type of dosing do these patients need in a long-term extension? Is a Q quarterly dosing optimal or for those patients who have very deep responses, could they even go on to a Q six-month dosing regimen? So we look forward to sharing those data with you in the first quarter of next year.

Thank you. and our next question will come from Jay Olson from Oppenheimer. Your line is open.

Oh, hey, congrats on all the progress across so many different clinical development programs and thanks for taking the question. Since your work at EADV linked early increases in IL-10 and TGF-beta-1 changes to subsequent clinical improvement, Are you also looking at whether those same early biological changes might predict sustained responses after treatment withdrawal? And if so, would those findings strengthen the case that RESPEG is potentially disease modifying by restoring immune regulation rather than just reducing temporary suppression of inflammation? And then if I could, as a Can you just talk about any update on your type 1 diabetes program and when we should expect to see clinical data? Thank you.

I'm happy to take the first question. And so that is indeed, as you telegraphed it, a suite of activities that we're doing. Because in this study, the cohort is large enough. That we have the ability to parse the patients and look for different features of the responses. And we are indeed looking at both the skin as well as the serum for any hallmarks associated with those kind of stratifications of the responses. We're doing that first in the 16-week induction data, and we presented just a portion of the data. There's much more data than was presented by Meredith in that EADV presentation. But importantly, we also collected tape strips through 52 weeks in that study, as well as serum samples. And this is indeed, you know, a significant area of our translational focus because we do believe that we're able to see features, you know, of the kind of normalization as well as the immune changes that could be consistent with, you know, really the rebalancing mechanism of RASPAC. So this is going to be definitely the subject of additional work that we're doing. And Mary, maybe I'll turn the type 1 diabetes question over to you.

Yep, thanks, Jaycee. Yeah, thanks, Jay. Yeah, so I know the trial net has probably about two-thirds of their clinical sites that they plan to enroll to up and running. And the first cohort will be 18 patients, 12 on RESPEG and six on placebo. And so they're anticipating having the data from that first cohort, the six-month data, either at the end of 2027 or the beginning of 2028. So we're really excited and looking forward to seeing those data as well. Thank you.

Great. Thank you. Congrats again.

Thank you. And our next question will come from Cha Cha Yang from Jefferies. Your line is open.

Hi team. This is Cha Cha on for Roger. Thank you again for this very informative call and thank you for taking my question. I also have a question on the vitiligo selection program. If you could tell us more about How you are choosing patients and which patients you're choosing to prioritize, whether that's active disease patients or patients with stable disease where the goal might be primarily repigmentation. And then in relation to that, if you could tell us about the percentage of patients for each and the commercial opportunity for targeting certain subgroups of patients that you're going after. Thanks.

Yeah. Hi, Chacha. So we are going to enroll patients with active disease, and these are patients with non-segmental vitiligo. and we were just mentioning that this is a fairly large market, very similar, we're looking at this market very similar to alopecia areata. We are working with our advisors, like I said, just actually speaking to David Rosemarin this morning about some of the specifics of the study design and as we get our trial up and running, we will let you know in more details about the total patient population and the exact design of the study and our anticipated date for having data. So thank you.

Thank you. And our next question will come from Tara Bancroft from TD Cowan. Your line is open.

Hi, good afternoon. I was hoping maybe you could give us an update on how you're seeing enrollment progressing in the biologic naive versus experience phase three studies. Trying to see if you're seeing any particular headwinds or tailwinds in either, and if you're expecting that these trials are going to complete enrollment in a similar timeframe, just as we're thinking ahead about the cadence of data. Thank you.

Yeah, thank you for asking the question. So, you know, we are, you know, just getting started and I would say, you know, right now, not a huge difference between enrollment between the naive and the experienced patients and all of our enrollment projections for all three of the AD trials, we believe, you know, are all going to coalesce and finalize and have our top line data by the summer of 2028. So that means all the patients will be enrolled to these trials around January of 2028.

Thank you. And our next question will come from Samantha Semenko from Citi. Your line is open.

Hi, good afternoon. Thanks very much for taking the question. Just on the ZENUS-82 study, can you talk a little bit about the regulatory feedback that you received that led to the change in the protocol? What drives this feedback from regulators? And can you say which regulatory agency initiated the feedback? Thank you.

Hi, Sam. Well, you know, we have received regulatory feedback from the United States, from the FDA, from the EMA, and from the PMDA, from the Japanese Health Authority. I will say that, you know, it's not always the exact same, but everybody agrees that having a clinical trial in combination with topical corticosteroids is, you know, a wise way to go. I think what's changed probably from when Dupixent and Leberkizumab and Trilokizumab started their development programs is it was more common to do two clinical trials in naive patients and a third trial in topical corticosteroids. And I think as the evolving landscape has more people treated with biologic, certainly doing a study in patients who are experienced with something and feedback that all the regulators had shared with us I'll just finally state that in Japan, for registration there, you have to do a trial in combination with a topical corticosteroid. So the totality of the feedback that we got from all three agencies really made it very clear that the best way to strengthen our overall phase three registrational package to support the broadest possible label and meet the needs of all three regulators was to change that AD2 study to a topical corticosteroid. So it wasn't one, it was a combination of all three and it really was the totality of their feedback really helped us strengthen our overall program for commercial purposes too.

Thank you. And our next question will come from Will Sohikian from LeRinc. Your line is open.

Great. Thanks for taking the question, guys, and congrats on the progress this quarter. I do have a follow-up to the Zenith 82 study. So just on the adjustment that you guys did, does the addition of TCS cause a sample size change or a powering assumption change as well? What placebo plus TCS response are you guys assuming, and is there a cap or stratification factor on experienced patients that we should be mindful of here? Thank you. Yeah.

Yeah. Thank you. So, you know, to take the last part first, the stratification factors, when you look at the ROCA's OX40 data where they enrolled experienced and naive patients, and if you look at the ADHERE trial, which was the Leberkizumab-TCF combination study, Both of those studies did exactly what we're doing, which is stratifying on geographical location, age, and disease severity. And when you look at those trials, they were both well-balanced in terms of prior biologic use versus not. and because this trial is so large, 510 patients, we have no worries just like in the ROCA trial and even the ADHERE trial which is only 211 patients. They had very well balanced experience and naive patients given the stratification factors. And then in terms of power calculations, all of these studies are very well powered, 99%. and the reason that the trials are so large and that we have a 1500 patient overall phase three program is really to collect adequate one year safety data. So the trial in topical corticosteroids is adequately powered and over 90% power to detect the statistical difference and in terms of, you know, looking at other clinical trials, you know, it's a benchmark for you. In the TCF studies, both the placebo arm and the treatment arms are slightly higher, not dramatically higher, but slightly higher than what you see in the monotherapy studies. And you can look in the DUPI, the TRALO and the LEBRY trials. They all ran two naive studies as well as one TCF study. So you can compare. you know the EEC75 and the IGA results of those you can see slightly higher but not dramatically higher and the delta between the two is still quite robust and they reached very strong p-values in the TCF studies as well as the naive studies because again these trials are so overpowered for safety purposes and not based on efficacy.

Thank you so much.

Thank you. Our next question will come from Arthur He from HC Wainwright. Your line is open.

Hey, Howard and team, and congrats on the progress. So, I have two questions. So, one is, could you give us more color on what moved the Zenos AA study earlier? What have changed after you last time update us for the early 2027 start compared to now, according to December? The second question is, could you remind us how you guys plan to evaluate the off-drug activity for RASPAC in the ZENUS AA study? Is there any randomized period after the Week 52?

Great. Yes. Thanks, Arthur. You know, Nectar has a very experienced and highly committed and very competent team in their clinical development and clinical operations and biostats and drug safety. And they're really able to move mountains. So the team was able to write the protocol, submit it to the health authorities, build the system, make sure there's an ICF, develop budgets, and go out and train the sites. and they were all able to do that ahead of schedule and I think it really speaks to just how highly experienced they are, the incredible leadership and the dedication. Likewise, I think there's a lot of motivation among the dermatologists that we've met to participate in the study because a lot of their patients don't want to go on a JAK inhibitor So that, you know, addresses your first question. And your second question is, you know, off drug. No, you know, we plan on moving patients after 52 weeks into those patients that have deep responses. We'll randomize those patients into a monthly and quarterly dosing. And for those patients, you know, who haven't hit a salt 20 yet. As you'll recall, when we looked at the shape of the curve, the trajectory of the curve, the slope of the curve, it continued upward. And we really believe that those patients who haven't hit a SALT20 yet with ongoing Q2 week dosing, we can convert many more patients as we have not seen a plateau effect. So those patients who don't have a SALT20 will continue on a Q2 week dosing. So we do not have a model in our long-term extension to withdraw treatment. Thank you.

Thanks, Mary.

Thank you, Arthur.

Thank you. Our next question will come from Mayank Mumtani from B. Riley. Your line is open.

Hi, Mike. I'm from Mayank. Thanks for taking our question and congrats on the quarter. For the RESULT-80 data coming out in the first quarter of 2027, which patients will come off drug and how would you define and maintain response there? Like what would be the end point? We know that in levacruzumab, about two thirds of patients that switched to placebo were still EZ75. So how would a Treg drug like Respec do something different here? And from the alopecia data, we know that patients who dosed to week 52 held response far more than those who stopped at week 36 and the response kept deepening. Should we expect that here in AD? And finally, on the new vitiligo, the new vitiligo that you're going into, Argenix has a vitiligo acid that is an L2 inhibitor, and Respec here is sort of an L2 agonist. So how does that kind of work here? Thank you.

Yeah, great. Thanks, Mike. I'll take the first question, and I'll pump the second one to Jay Z. Our goal has always been to create a therapy that enables less frequent dosing while maintaining durability of responses. And our objective is to give patients a more convenient and flexible dosing schedule after an initial treatment period. And so what we're able to do in our phase two study, which to the best of my knowledge, no one has been able to do, is evaluate what is standards, a 52-week treatment, which includes an induction phase and includes a maintenance phase. And then we're able to look at what happens to those patients off treatment and assess and evaluate the durability of their responses. And we're doing this specifically because we want to know after one year, you know, what type of dosing can help patients maintain their responses and are there some patients who could even go to an every six month dosing period and those patients who could continue on a quarterly dosing regimen. So we think we'll have very good data with 125 patients to evaluate these questions. And then regarding the vitiligo question, I'll ask Jaycee to comment.

Yeah, thank you, Mary. And so, yeah, basically, you asked the question about Argenix has an anti-CD122 antibody that was the acquisition from Borte. And also IL-15 blockade has demonstrated some activity. Basically, those are kind of, I see them almost sort of like an extension of the JAK inhibitor mechanism. So with a JAK inhibitor, you're blocking the same cytokine pathways that IL-2 uses and IL-15 use. So those are mechanisms that are aligned to reduce inflammation, particularly interferon gamma and some of the type 1. Raspeg's mechanism is, of course, different, right? We're inducing a cellular mechanism. We're activating a cell population. Our aim is to restore the sort of the missing counter-regulatory mechanisms that are defective. in the case of vitiligo or in the case of alopecia. So they are related. They're similar axes. They're approaching this in two different directions. And obviously, we're very excited to kick off the vitiligo study and very confident about that study and the mechanistic translation based on what we've seen in alopecia and atopic dermatitis. Thanks.

Thank you. Our next question will come from Jessica Tsai from J.P. Morgan. Your line is open.

Hi, this is Jose for Jess. Thanks for taking our question. For the uptreatment data set coming up in the first quarter of 27, how many patients will there be? And could you remind us of your expectations for Respex effect size in biologic experience patients compared to 90 patients in A.J.? Thank you.

Yeah. Hi, so we have 125 patients that entered into the long-term extension. Of the 125 patients, 110 of them were actually on RESPEG in the maintenance period, and 15 of them were on placebo, and those 15 patients are carried through simply to maintain the blind. And then, you know, with respect to biologic experience and biologics, and many other naive patients. What we've seen so far, even with the IL-13s of leprakizumab, the efficacy in patients who have been previously treated with dupixent is relatively the same. And we believe we have an even stronger mechanistic rationale for why we will see very similar efficacy. because unlike the cytokine blocking agents that merely can really address a TH2 disease patient, we do know that atopic dermatitis is a very heterogeneous disease where patients have TH1, TH2, TH17 disease phenotype and going upstream, and being able to increase T regulatory cells, which could have an effect on all those phenotypes. And that's also cooperated by the data that was presented at EADV with the ability to normalize TH1, TH2, TH17 and fibrosis. Thank you. Thank you.

Thank you. And our next question will come from Kelsey Lucerne from William Blair and Company. Your line is open.

Hi, this is Kelsey on for Andy. Thanks so much for taking our question. We were curious, kind of taking a regulatory perspective, with ZENUS 82 now including both naive and experienced patients, How should we think about Zenith 83's incremental role in the registrational package? And is success in Zenith 83 necessary to support use in previously treated patients? Or could positive 81 and 82 results support that broader label? Thanks.

Hi, Kelsey. This is Mary. Yeah. So, you know, we really wanted to have the best and so on. And so, you know, the ZNF-AD1, that's really, you know, naive patients and we can think about that as a first-line patient population. And you think of the AD3 study as those experienced patients, so these are really patients who would be second or third line. So those are two different subsets of patients. In both of those studies, we're enrolling adolescents age 12 to up to 18. And then when you add AD2, now you're adding the combination with topical corticosteroids. And in that study, again, we have adolescents and we have experienced and we have naïve. So the way we look at this is a very strong, robust, overall based re-registrational packet that includes the broadest label there is. First line, second line, third line, combination, adults and adolescents. And then with respect to your regulatory question, We really view the ZENUS-AD program as an integrated package rather than looking at any one simple study as backup for another. That being said, you do need two successful phase threes for registration. So we're believing due to the power of these trials that we will see three positive studies in the event that one isn't. then we have certainly the opportunity to speak to regulators about a path forward for registration. But certainly we've built this program as an integrated registrational package rather than looking at any one as just a backup to another. Thank you.

Thank you. Our next question will come from Alice Nettleton from UBS. Your line is open.

Hi, thank you so much for the question. You seem to have benefited from the setbacks with OX40+, which makes sense. There are several atopic derm competitor readouts coming up, including STAT6 and various bispecifics and trispecifics. If any of these were to have setbacks also, could this also benefit RESPEG, or do you view the target patient populations differently such that it wouldn't have much of an impact? Thank you.

Let me take a stab at that. I think, look, clearly setbacks from one company potentially benefit another company, but I don't really look at it that way. I actually don't want to see companies fail. And quite frankly, the market for ectopic dermatitis is so significant and so large. even a 10% market share puts you at a potentially $3-4 billion product. So I think there's a lot of room for different drugs. The heterogeneity of the disease certainly means that patients aren't going to be Well treated by only one mechanism and certainly IL-13, while it does incredibly well and it's an important mechanism, it isn't the solution for ectopic dermatitis. So while I do want to see other companies succeed, I do think the market is large enough for all of us and the disease is not very well treated right now. As we said earlier, half the patients who take an IL-13 ultimately fail that therapy. So large market, lots of opportunities. and I hope everybody does well there. Mary, is there anything you want to add to that?

No, I think that's a great answer, Howard. Nothing to add.

Thank you. And I am showing no further questions from our phone lines. I'd now like to turn the conference back over to Howard Robin for closing remarks.

Okay, well thank you again everybody for joining us today and we are entering an important period for Nectar focusing on executing on registrational programs. It's a great position to be in We believe RESPEC has the potential to establish an entirely new approach to treating autoimmune, to treating immune mediated disease and our focus now is squarely on carrying out the phase three plan and bringing this potential therapeutic option to patients as quickly as possible. I want to thank all of our employees for their hard work and dedication and we look forward to updating all of you on our progress. So stay tuned.

Thank you. Thank you for your participation. You may now disconnect. Everyone have a wonderful day.