Ladies and gentlemen, thank you for joining us, and welcome to Nektar Therapeutics' Analyst and Investor event to discuss REZOLVE-AA top-line results. After today's prepared remarks, we will host a question-and-answer session. If you'd like to ask a question, please raise your hand. If you have dialed into today's call, please press star nine to raise your hand and star six to unmute when prompted. I will now hand the conference over to Vivian Wu, Investor Relations and Corporate Affairs. Vivian, please go ahead. Thank you, and good morning, everyone. Thank you for joining us today. Today, you will hear from Howard Robin, our President and Chief Executive Officer, Dr. Jonathan Zalevsky, our Chief Research and Development Officer, and Dr. Mary Tagliaferri, our Chief Medical Officer. Our KOL panel and renowned experts in dermatology and alopecia areata, Dr. Jonathan Silverberg, Dr. David Rosmarin, and Dr. Benjamin Ungar, will also be available during the Q&A portion. On today's call, we expect to make forward-looking statements regarding our business, including statements regarding the therapeutic potential of and future development plans for rezpegaldesleukin, the timing and plans for future clinical data presentations, 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 control. Our actual results may differ materially from these statements. Important risks and uncertainties are set forth in our Form 10-Q available at sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of new information, future developments, or otherwise. A webcast of this call will be available on the IR page of Nektar's website at nektar.com. With that said, I would like to hand the call over to our President and CEO, Howard Robin. Howard? Thank you, Vivian. Good morning, and thank you, everyone, for joining us today. Over the past several years at Nektar, our strategy has been to advance innovative therapies for serious autoimmune and inflammatory conditions, with a focus on regulatory T cells as a modality. Our work has been driven by early proof-of-concept data signaling to us the potential for this first-in-class mechanism to treat a range of autoimmune and inflammatory conditions, particularly dermatological diseases. This year, we reported positive phase II-B data in atopic dermatitis, including patients with comorbid asthma, that get us one step further to bringing a Treg biologic to patients. We're pleased to share today the compelling proof-of-concept results from our phase II study in alopecia areata, and we believe the results from these two studies establish that REZPEG, a first-in-class Treg stimulator based upon IL-2, has now been shown to be a best-in-class approach. In the REZOLVE-AA study of REZPEG and alopecia areata, we achieved our target product profile, which was to both demonstrate comparable efficacy to a low-dose JAK inhibitor and establish a favorable safety profile that could offer the potential for a much-needed biologic therapy to patients with severe to very severe alopecia areata. We know that more than half of dermatologists are hesitant to use a JAK inhibitor for their patients, and we believe the highly promising data we're presenting today provide a strong basis to advance REZPEG into phase III development in this patient population. And with that, I'm going to hand the call over to J.Z. and Mary, who will walk you through the results. J.Z.. Thank you, Howard. I'd like to start by summarizing the phase II program for REZPEG, which is underway in atopic dermatitis, alopecia areata, and type 1 diabetes. In atopic dermatitis, we presented outstanding efficacy data results for REZPEG. Our large phase II-B study, which is still ongoing, validated the therapeutic potential of a Treg MOA in a large chronic disease setting. Besides dupilumab, REZPEG is the only biologic in development that has shown clinical efficacy data in patients with atopic dermatitis and asthma, a comorbidity which occurs in one of four patients. We look forward to reporting results from the 52-week maintenance portion of the REZOLVE- AD study in the first quarter of next year. For alopecia areata, we believe the results we're showing today clearly demonstrate that REZPEG has achieved proof-of-concept. As Howard said, REZPEG met our target product profile with activity, with a treatment effect comparable to low-dose Olumiant, but with a completely differentiated and better safety profile, and finally, our partner TrialNet recently initiated a phase II trial in patients with new-onset stage three Type 1 diabetes and a new indication for REZPEG, and overall, we are very pleased with the progress we have made with REZPEG across this phase II program. There is a high unmet medical need and patient need for an efficacious and safe biologic that can be used to treat patients with severe to very severe alopecia areata. Currently, the approved JAK inhibitors are effective at regrowing hair in some patients, but they carry a number of drawbacks, and more than half of physicians want to start in first line with an alternate therapy because of the risks and the monitoring burden they pose. Moreover, these drugs require continuous dosing to maintain efficacy, and up to 90% of patients eventually rebound after stopping therapy. As this slide shows, the limitations of JAK inhibitors open a major opportunity for a biologic in this indication. About 30 years ago, in 1995, Dr. Shimon Sakaguchi identified a subset of lymphocytes called regulatory T cells that were critical to immune tolerance. And six years later, doctors Mary Brunkow and Fred Ramsdell cloned the FOXP3 gene from the scurfy mouse, identifying the critical transcription factor that controls their function. Together, these three scientists won this year's Nobel Prize for Physiology or Medicine. We are thrilled that Tregs have been recognized and humbled that REZPEG was named, and our Nature Communications publication was cited in the scientific background document accompanying this year's prize. And this figure shows why we're excited. It's a depiction of why and how targeting Tregs could be a good approach to address a range of autoimmune diseases driven by underlying T helper cell pathologies. We know that certain polarities of T cell inflammation underlie inflammatory diseases such as atopic dermatitis, alopecia areata, psoriasis, asthma, and others. And the key point is that Tregs have been shown to polarize to the effector T cell type and thus could provide control for many different inflammatory diseases. And I will now turn the call over to Mary to review the REZOLVE-AA study results. Mary. Thank you, J.Z.. I will start with the key questions that we wanted to answer with the REZOLVE-AA study. Importantly, this study is the first time REZPEG has been evaluated in patients with alopecia areata. To that end, it was designed as a signal-seeking study to evaluate the biological activity and clinical efficacy of REZPEG in these patients. In REZOLVE-AA, we needed to ask these questions for the first time in this disease setting, which is a different patient population from the other skin disorders we've studied with different disease attributes. The first question we wanted to answer is whether a Treg biologic drug with infrequent dosing could offer meaningful clinical benefit and a favorable safety profile compared to available therapies. At the time we started this trial, we had a fair degree of compelling safety data across multiple prior trials, but we wanted to understand longer-term every two-week dosing safety and whether we could differentiate from JAK inhibitors. Second, we needed to understand what the kinetics of hair growth were with a Treg mechanism. As we knew that a longer induction for hair regrowth might be needed based upon the studies evaluating DUPIXENT in this setting, we chose a 36-week induction period for the primary endpoint with a 16-week extension. Third, we wanted to know the optimal dose of REZPEG for phase III advancement. We believe we have successfully answered these questions with our results. Shown here is the design of the phase II-B trial. We incorporated standard eligibility criteria into the study, which included patients with severe to very severe AA with a SALT greater than or equal to 50. The study is being conducted in 92 adult patients with severe to very severe alopecia areata. Patients receive treatment every two weeks with subcutaneous REZPEG 24 mcg per kilogram, 18 mcg per kilogram, or placebo. The primary and key secondary endpoints shown here were assessed at the end of the 36-week induction period. Patients who had hair regrowth at week 36 but did not achieve a SALT 20 score or better had the opportunity to enter a 16-week treatment extension of their dose arm, and at the time of this data cutoff, we have 23 patients ongoing treatment in the extension portion of this study. Finally, all patients are followed for an additional 24 weeks off therapy. Today, we will present the primary endpoint along with the key secondary and exploratory endpoints. Details of the statistical analysis methods are shown here. For the primary endpoint of percent change from baseline in SALT at week 36, the study was designed with 95% power to detect a 23% delta between treatment arms and placebo. The study was not statistically powered for the secondary endpoints. With respect to baseline demographics, 64% of the patients were enrolled in Poland and 36% from North America. The median age was 39 years. At baseline, the average SALT score was 78, indicating a high severity of alopecia. The average time since diagnosis of alopecia areata was 11 years. The protocol capped study enrollment at 25% for very severe patients. For this trial, patients received every two-week treatment, with some patients receiving up to 52 weeks of treatment. This represents the longest twice-monthly dosing duration studied in the REZPEG program, and we are pleased to say that the safety profile is very favorable and there were no new safety findings. Nearly all AEs were mild to moderate in severity and self-resolved. Only one patient discontinued due to an AE on the REZPEG treatment arms. The placebo-adjusted ISR rate was consistent with prior studies, and no patient discontinued due to an ISR. 87% of the ISR events were mild in nature. Of importance for patients with AA, there were no indications of increased risks associated with MACE, thrombosis, infections, or other untoward side effects such as acne or oral herpes. Importantly, the known AE profile of REZPEG should not require the extensive laboratory testing or monitoring typically associated with JAK inhibitors, so here's the patient disposition chart from the study. The majority of patients completed the study out to week 36. You can see that approximately 60% of those patients that completed week 36 moved into the 16-week treatment extension period. Most of the patients who entered the treatment extension period are still ongoing. Overall, the discontinuation rate in the placebo arm was higher than the drug arms, and more patients discontinued before week 16 than after. 75% of the patients who discontinued for patient decision did so before achieving a 30% reduction in their baseline SALT score. We believe this could be reduced in the future by educating investigators and patients about the kinetics of hair regrowth on REZPEG. Shown here is the primary efficacy endpoint of percent change from baseline in SALT for the modified intent-to-treat population, or all 92 patients who received at least one dose of study medication. Both REZPEG arms more than doubled the treatment effect compared to placebo. These data clearly establish clinical proof-of-concept for REZPEG in alopecia areata. While the curve separated from placebo at all time points, the treatment difference between REZPEG and placebo narrowly missed our critical delta of 23% between the drug arms and placebo. That said, there were four patients identified who had major study eligibility violations and who did not meet the strict pre-specified inclusion and exclusion criteria. These four patients were erroneously enrolled by investigators, and so today's presentations, all subsequent analyses, are post-hoc with an mITT population that excludes these four erroneously enrolled subjects based on objective criteria. Now let me show you what happens when we remove the four patients with major study eligibility violations. With this analysis, REZPEG has a fivefold improvement over placebo, and both arms achieve statistical significance. Importantly, REZPEG 24 mcg per kilogram was statistically significant at week 12 and at each time point thereafter. We believe these results further support REZPEG's potential as the first biologic for alopecia areata. Now, to provide more granularity on the eligibility violations, two of the four patients, one on placebo and one on REZPEG 24 mcg per kilogram, had unstable alopecia areata with their initial disease being diagnosed less than six months prior to randomization. So why is this important? Alopecia areata is considered unstable when patients have a diagnosis for less than six months because of the unpredictable nature of its autoimmune response, which can fluctuate in the early months with periods of hair loss and regrowth. Therefore, it's standard practice to exclude these patients from AA studies. There were also two additional patients excluded in this analysis who initiated treatment before completing the prerequisite eight-week washout period for other AA medications. This included one patient on REZPEG 18 mcg per kilogram and one patient on 24. Before moving on, I want to highlight that the curves of the REZPEG treatment arms are consistent with evidence of hair regrowth over time and show no evidence of a plateau. This trajectory is promising for continued hair regrowth beyond week 36, and we'll have the chance to thoroughly evaluate the benefits of REZPEG up to 52 weeks of treatment when we complete the 16-week extension part of the trial next year. Now, what we're showing here is critically important. On the left-hand side are the results for the mITT patients with the four patients with the major study violations. On the right side of the slide, the four patients are removed. As you can see, the REZPEG groups demonstrate essentially equal treatment effect, whether the four patients with the major protocol eligibility violations are included or excluded. In the MITT assessment, the placebo effect was roughly 11%, and without the four excluded patients, the placebo effect is 5.7%. As Howard and J.Z. stated earlier, REZPEG successfully met our target product profile of achieving a 30% reduction in SALT at week 36 compared to a low-dose JAK inhibitor. And as you can see here, presented is side-by-side data for REZPEG and low-dose Olumiant from two separate phase III studies. Shown here is a waterfall plot of the best SALT percent change at any time point on the study. Each bar represents an individual patient, and the blue bars are the pooled REZPEG-treated patients, and the gray bars are the placebo-treated patients. 42% of REZPEG-treated patients achieved a 30% or more reduction in SALT score, 36% achieved 50% or greater, and 17% achieved 75% or greater. All these numbers are well in excess of placebo. Now, any patient with a green dot over the bar is ongoing after 36 weeks in the 16-week treatment extension. The purple dots are those patients that completed 36 weeks, and the gold dots represent patients that have completed the extension. No dots over the bars represent the patients who discontinued before week 36. The key takeaways from this waterfall plot are, first, REZPEG-treated patients have experienced hair growth on the study. That's clear. You can see here that the majority of patients who did not complete 36 weeks of treatment cluster around the left side of the waterfall, where there is little to no change in SALT scores. This demonstrates that staying on treatment is important to derive maximal clinical benefit. Second, the 20 patients marked with green dots are ongoing in the 16-week extension and have the opportunity to experience further improvements in hair growth. The next five slides will highlight the dose-dependent results we observed across the key secondary endpoints. Similar to what we saw in our phase II-B study with atopic dermatitis, high-dose REZPEG 24 mcg per kilogram separates from 18, and so this will be the recommended phase III dose. In these studies, it is common to also evaluate data in the severe patient population because these patients are most likely to have robust responses earlier. Since we had 23 and 25 patients in the severe populations for the 24 and 18 microgram per kilogram doses, respectively, we assessed the efficacy in this subgroup. You can see here improved efficacy in the severe patient population for high-dose REZPEG, and this effect size looks quite similar to low-dose Olumiant. Shown here are the REZPEG responders who had at least a 30% reduction in SALT as compared to this same endpoint from a reported study that evaluated DUPIXENT for AA. The data shown on this slide indicate that REZPEG is more than twice as effective as DUPIXENT in a similar size study. Recently, new Delphi consensus guidelines for severe alopecia areata recommended DUPIXENT as a long-term treatment option for patients with alopecia areata who have active atopy or a history of atopic dermatitis. Given the major unmet need for a safe biologic as an alternative treatment to JAK inhibitors, the totality of the data presented thus far supports that REZPEG could be a real breakthrough for patients with AA. Now, the next three slides show the results for the responder analyses for absolute SALT scores achieved in the study. This is SALT 30, SALT 20, and SALT 10, or said differently, patients that regrew 70%, 80%, or 90% of their hair. All three analyses illustrate that REZPEG demonstrates a clear dose response, has an early separation from placebo, and shows a consistent treatment effect across the FDA and EMA registrational endpoints, particularly with the deeper response analyses, 24 mcg per kilogram is superior to 18. Here are the SALT 30 responses. Note that 29% of patients on 24 micrograms per kilogram regrew at least 70% of their hair. And then here are the SALT 20 responses. This is the registrational endpoint for the FDA. As you can see, this curve goes through to week 36 with a clear separation from placebo. We've already seen three additional patients achieving a SALT less than 20 during the 16-week treatment extension period, and these patients are not included in this analysis since they achieved SALT 20 after week 36. Moreover, there are currently seven more patients that have reached SALT less than 30 by week 36 and are ongoing in the 16-week extension and who can continue to regrow hair out to week 52. We look forward to seeing these patients' data in the next year. Now, just like with our atopic dermatitis program, the REZPEG 24 mcg per kilogram has emerged as the favored dose across multiple primary and secondary endpoints. These data from the REZOLVE- AA trial make the selection of REZPEG 24 micrograms per kilogram an obvious choice for our recommended phase III dose. Of note, the placebo-adjusted SALT 10 responses shown here, which is an EMA-approved endpoint, are similar to what you see with low-dose Olumiant. And then here are the clinician-assessed outcomes for the improvements in hair growth for the eyebrows and eyelashes. It's important to see that the MOA of REZPEG has the ability to impact additional hair follicles beyond those in the scalp, and this potential is demonstrated by patients regrowing eyebrows and eyelashes with an effect similar to reported data with low-dose JAK inhibitors. So we started out this call sharing with you the key questions we set out to answer, and this study delivered what we needed. We now have demonstrated proof of concept, and we know every two weeks subcutaneous dosing of REZPEG demonstrates a clear and consistent separation from placebo on all measures of efficacy. Likewise, we see a clear dose response, and we have identified REZPEG 24 mcg per kilogram every two weeks as our recommended phase III dose. Given what I have shared regarding the ongoing responders in the extension period and with the most profound increases in hair growth beginning after week 16, we will choose 52 weeks as our induction period for the registrational program. Now, I'd like to share six cases from the REZOLVE-AA study. Shown here is a 66-year-old woman who received 36 weeks of REZPEG 24 mcg per kilogram. You can see this patient who is nearly bald has regrown 90% of her hair. For 16 weeks, this patient did not experience hair regrowth. After that time, the patient experienced relatively fast hair regrowth and eventually achieved a SALT 20 response by week 36. What is noteworthy about this case is the ability to treat patients with high SALT scores at baseline and safely treat patients in their 60s who could have comorbidities that would preclude them as optimal candidates for JAK inhibitors given the multiple black box warnings. And then here's a case where a 40-year-old man experienced improved efficacy with extended treatment. In fact, this patient entered the extension and achieved a SALT 20 score at week 44, and cases like this support our planned 52-week induction period for the phase III program. On this slide, you can see a 20-year-old young woman who was diagnosed with alopecia areata six years prior to treatment, and she started out with marked hair loss. She has consistent hair regrowth after week 20, as shown by her SALT graph to the left, and she has advanced to the extension period where she may continue to experience ongoing clinical benefit from REZPEG. While we did see a clear dose response with REZPEG 24 mcg per kilogram showing superior efficacy to 18, several patients also experienced meaningful clinical benefit from 18 mcg per kilogram. Here is a young woman with AA for 17 years who achieved a SALT score of 20 by week 28. It's really not hard to imagine how a young woman's self-esteem, confidence, and quality of life would be dramatically improved when you go from an appearance shown in the photos on the top of the slide to the ones on the bottom. Shown here is a 64-year-old woman who was diagnosed with AA later in life. This is a case where the patient's clinical benefit with REZPEG was delayed. She notably reached a SALT 20 during week 44 of the extension phase of the trial and continued to deepen further to week 52. Again, as I've mentioned on this call, there is evidence that a 52-week induction period for the phase III is the optimal time period to capture both early and late responders. Shown here is another patient who is nearly bald with ongoing new hair growth in the extension phase. On the right side of the slide, you can see the regrowth of his eyebrows. Again, it's really not difficult to imagine the improvements in overall well-being, confidence, personal satisfaction, and happiness when very young men and women are able to regrow hair. With all that, let me summarize the key takeaways from the REZOLVE-AA study. Most importantly, the study results demonstrate proof of concept for REZPEG as a first-in-class biologic for the treatment of alopecia areata. We are very pleased that REZPEG achieved our target product profile for favorable clinical efficacy and tolerability with a differentiated safety profile. Our target product profile was designed to meet the urgent unmet medical need for a safe alternative to the JAK inhibitor class for alopecia areata. We're also pleased to share on this call today that in two different inflammatory skin diseases, we have identified REZPEG 24 mcg per kilogram as the optimal dose to proceed to phase III. And with that summary, we will introduce you to our KOL panel and renowned experts in dermatology and alopecia areata, Dr. Jonathan Silverberg, Dr. David Rosmarin, and Dr. Benjamin Ungar. Before we take questions, we would like to ask each of our KOLs to provide their assessment of the data. Dr. Silverberg, can you please go first? Then we will ask Benji and David, and David will share his own patient case study. Then we'll open up the Q&A to our KOL panel as well. So, Dr. Silverberg? Sure. Thanks very much, Mary, and excellent presentation. I mean, overall, I'm very excited about the data. From a broader scientific perspective, I think the data are really cool because they show that proof of concept upregulating Tregs is a viable strategy in alopecia areata, and I think provide further support for the Treg hypothesis. But particularly within alopecia areata, these are the best data we've seen for a clean biologic. The field sorely needs a clean biologic without the laboratory monitoring or boxed warnings. There are a lot of dermatologists and patients who are scared to use JAK inhibitors, and we see very clearly from atopic dermatitis, other inflammatory skin diseases that a clean biologic will be preferred by patients and providers probably nine out of ten times over medications that come with the complexities of boxed warnings and laboratory monitoring. So I think REZPEG would be very well received within dermatology. Obviously, the purpose of this study was to inform the design of the phase III, and I think we got everything we need to optimally design the phase III. There's a clear dose response. It's clear that the 24 mcg dose is the preferred dose to study in phase III. It was a relatively small study, but there were clean and consistent kinetics curves, which will provide clear guidance on how to power the phase III study. The efficacy in the study is similar to Olumiant in the first 36 weeks, but when you look at the trajectory of the curves, there's no asymmetry. There's no plateau of efficacy, and that really suggests that continued dosing would lead to even greater efficacy over time. So that has its own important ramifications in terms of long-term efficacy, but I think it also informs that we're going to get even better efficacy at week 52. So I think we have everything we need. I think there's a clear and strong case to move into phase III, and I think REZPEG can be a really big success in alopecia areata. Thank you so much, Jonathan. Benji, can we have you weigh in next? Sure. Good morning, everyone. Can you hear me? Okay. Yes, we can. Excellent. So good morning. Thanks, Mary. So I'm going to echo a lot of what Jonathan said because the short version here is that I'm quite excited about these data, and I'm quite excited about REZPEG as a potential treatment for alopecia areata. So I see many, many patients with severe alopecia areata. I speak with many colleagues who see patients, and so I'm quite aware of the landscape that exists both in terms of patient really demand for treatments and my colleagues' appetite for alternative treatments to JAK inhibitors. The advent of JAK inhibitors really has made a huge difference for many patients' lives, but the reality is that a very small subset of patients who really should be treated with the systemic therapy are currently receiving treatment, and that's primarily because of the limitations and hang-ups that exist around JAK inhibitors. And so when patients are seeking treatment, they're very motivated to get treated, and so they, in many cases, will take the best of the available options, in this case, the JAK inhibitors, but they really look for alternatives. It's a common theme in conversations with patients, patient conferences, and frankly, that's one of the reasons why in the consensus guidelines that Mary referenced earlier, and I was one of the authors on that, we included a recommendation for alternatives, in this case, DUPIXENT, because there are patients and physicians who are just not going to use JAK inhibitors. And so the potential for another treatment that has a clean, safe profile that's easy to prescribe and will lead to benefits, really, it's just hard to overstate just how much of a desire there is for a treatment like that. Now, with that said, we still need to look at what the data suggests about this specific treatment that may fill that niche, and the data that Mary presented are quite encouraging, so Jonathan referenced the fact that there's no plateauing. This is a mechanism that I would expect to take a number of months. This is exactly actually the efficacy curve that I would expect, and I have very little doubt that when we extend time points beyond the 36 weeks that was the endpoint here, we're going to see continued improving efficacy beyond that, and so the fact that there is this very clear response with a safe profile, no anticipated lab monitoring, really is extremely exciting, and I can think of numerous patients of my own that would jump at the opportunity to receive a treatment like this, so I'll stop there. I'm happy to answer questions on any of those points or others beyond that, but the kind of summary here is that this is extremely encouraging, and I think if everything pans out as the study so far projects, there's a significant potential for this treatment. Thank you so much, Benji. And then we'll have David actually share his own personal experience with REZPEG. Vivian, can you move to the next slide? So first, I want to echo my colleagues and agree. I think this is a big deal. It's the most effective targeted treatment tested for alopecia areata. And why? This is set up to be first-line therapy for alopecia areata. I'm very excited to see a phase III. I think we can be highly confident it will be successful, and I completely agree with my colleagues that the questions needed to successfully design a phase III have been answered, so it should be designed successfully. It's going to improve access to many of my colleagues who currently may be hesitant to prescribe JAK inhibitors for alopecia areata, and it's going to help a lot of people. I also think it can expand access to patients with more moderate disease with potential for an enhanced indication beyond just the severe, very severe population. So it's exciting, and I also want to add, I'm speaking on my own behalf, not Nektar nor my employer, and I'll introduce this patient of mine from the study. This is a 20-year-old Caucasian male who has had alopecia areata for about eight years. He previously was in a topical JAK inhibitor study, which he had no regrowth from. Subsequently, he enrolled in this trial, and at about the four-month mark, started to see some hair regrowth, and you can see by the end of the study, he already had some significant regrowth. What you also may not be able to appreciate from the pictures is some of the hairs were long and blond, and sometimes that happens when patients first regrow their hair, and it subsequently becomes the normal color for hair. And I strongly suspect that that's what will subsequently happen over the next few months. Also, he had some regrowth of his eyelashes as well, which I think is also notable. And by the end of the treatment, he did not want to come off this study drug, although he had to per protocol. He did have injection site reactions throughout the study, which for him was just redness. I never got to see them because they were in between the study visits that he experienced them, and they were not painful at all, and he did not mind them, so to me, this was really exciting because this is the reason why, again, I go into dermatology to help people like this, and to me, again, this is a big deal, and it's an exciting day. Thank you so much, David and Jonathan and Benji. We really appreciate these comments, so now we'll open up the call to any questions, and certainly, we're very happy to have our prestigious panel here with us. Thank you. We will now begin the question-and-answer session. Please limit yourself to one question. If you would like to ask a question, please raise your hand now. If you have dialed into today's call, please press star nine to raise your hand and star six to unmute. Please stand by while we compile the Q&A roster. And our first question comes from the line of Yasmeen Rahimi with Piper Sandler. Your line is now open. Please go ahead. Good morning, team. Congrats on the great data, and Mary, wonderful to have you back and hear your voice. Our first question is just in regards to the four patients that were excluded. I think on slide 13, team, it just says in the mITT analysis, there were these four patients that had the violation, but then it says post-hoc. Could you maybe help us understand what that means? I guess since they violated the protocol, they should not be eligible. I just want to understand what that post-hoc refers to when speaking about the four patients. That's question one. And then the second question is a quick one. On the safety table, there were on the bottom line, it says investigator determined AEs. If you could just help us understand what those were qualified as, that would be great, and I'll jump back into the queue and congrats on the outstanding data. Thank you very much. So when you write a statistical analysis plan, frequently in large trials, you include all randomized patients that received one dose. This is a smaller phase II-B trial, but we certainly employed the strictest statistical analysis plan. In addition, in statistical analysis plans, you always have per protocol analyses, and in this case, in this analysis, removed four patients that were ineligible. And you can imagine in a small study, when you dilute your trial with four patients with serious protocol violations that impact actual alopecia areata, you can imagine how that affects these patients. So these four cases were adjudicated by three medical monitors that were blinded to this study who all determined in unison that these four patients should never have been enrolled to the trial. We then did this analysis and clearly demonstrated a very clear efficacy, meeting our target product profile. And of course, that level of efficacy was seen in both the mITT as well as the mITT minus the four patients. So we're very excited that we have a drug that has strong biologic effect, especially for this indication where there's nothing else that patients can take except for a drug with multiple black box warnings. So thanks for asking that, and it's great to hear your voice too, Yasmeen. Thank you. Our next question comes from the line of Julian Harrison with BTIG. Your line is now open. Julian, your line is now open. You just have to unmute. Hi guys. Can you hear me now? Yes. Yes. Apologies about that. Congratulations on these results. My first question is maybe just reflecting on the data. Do you have any early thoughts on the remissive potential of REZPEG in alopecia relative to atopic dermatitis? And for the dermatologists on the call, what is your level of excitement for a drug here that has remissive potential specifically? And then second, taking a step back, can you remind us of your sense of REZPEG's scarcity value? IL-2 has been pursued by others before. What do you believe is uniquely enabling about REZPEG across diseases? Yeah, we will have that. Go ahead, J.Z.. Yeah, I was just going to say, so I mean, Mary presented data showing the extension and mentioning that we have already seen deepening of responses in that 16-week extension period. Three people have achieved a SALT 20 after week 36, and seven patients have reached SALT 30 by week 36 and are ongoing. And then our goal is to give an update in the second quarter about the 52-week data. And then Julian, the trial will continue because all patients will have a 24-week off-drug observation period, and we'll report those results in the second half of next year. But we designed the study with that off-drug observation, really looking to see if that activity that we've seen, this almost like infectious tolerance, is the immunological phenomenon that we see with Tregs that we observed in patients with atopic dermatitis, could further translate into these other indications like alopecia. So in the second half of next year is when we would provide those additional updates in the second quarter of 52 weeks and then beyond. And then I think I asked a question kind of about, well, actually, I'll turn it over to the KOLs about remissive potential before getting to your third question. Yes. And with the KOLs, as you address the remissive potential, can you also just address the difference between a once-daily oral dosing for the rest of somebody's life versus a Q2-week subcutaneous biologic? That would be helpful, I think, as well. Go ahead, David. You could start. Sure. So to answer your question, I am excited, but what I think matters most is safety is number one. So what determines prescriptions is safety by far. Then after that, I think it's the efficacy. And then after that, if it has a remissive effect, then that would be a cherry on top. But that, to me, will not drive prescriptions nearly as much as safety number one, especially in this disease state, and then after that, efficacy. I think a good analogy to look at is in Otezla. Why is it such a blockbuster drug within dermatology, even though its efficacy is quite modest in regards to the other options for psoriasis? It's because of its safety profile and the fact that it doesn't require lab monitoring. So if this drug doesn't require lab monitoring, that is a major bonus to prescriptions. And again, there are interruptions that happen all the time in treatment in the real world. So if there is an option that patients won't quickly lose their hair and have it fall out if they miss some treatment, well, then of course, that's a major advantage. And it's a bigger advantage in alopecia areata than in AD because if you're a 20-year-old female that has long hair and it's taken you years to grow that out, you don't want, in the course of a few months or a month or two, to start shedding that hair. That's very, very disturbing to patients. So having that remissive effect can be, again, a nice bonus. Thanks, David. And Jonathan, you want to weigh in too? Yeah, sure. I'd love to echo David's points. I agree completely. I think when you're looking at the efficacy profile, I mean, to your question, it's not, remission effect is cool, but that's icing on the cake, but I think there's a bigger story, which is really the longer-lasting benefit and the longer-lasting therapeutic efficacy, and the reason is because clinically, even patients who do well, you always see in market research, it always says an oral is preferred when all things are equal. But all things are almost never equal. And when you're dealing with something that comes with the box warnings and all the concerns, the patients go in starting a JAK inhibitor thinking, "Well, I'm going to take this for a few months. I'll stop it in like six months. I'll have all my hair back, and then I can quit, and then everything's going to be wonderful." And what they don't realize is all of a sudden, once daily oral, nine months later, really becomes a pain in the butt. It's hard to remember to take a medication every day for the rest of your life. And on top of that, patients routinely will endorse after struggling to regrow their hair in the first place. They missed the dose for a few days, and boom, they start losing their hair again. And so we need something with a more stable benefit. And based on this mechanism, we would expect this not to be one of these rapid-on, rapid-off effects, but really something that's going to have a much more stable effect. So I think this is really more of a long-term efficacy story first and foremost while on drug. But yeah, if there's a subset of patients where they can maintain stable clearance and full regrowth and then be able to eventually stop drug, obviously, that would be really cool. Thanks, Jonathan. We could wait for you, Benji, for the next question. How's that? That's great. Maybe I'll just really touch on you asked the scarcity value question, Julian. I think I'll just echo Howard's words. I mean, there were several approaches to target the IL-2 pathway and to create a drug that was scalable and easy to use for Treg mobilization. And I think we've now really clearly established that REZPEG is the correct design. It's the one that's survived through multiple clinical studies. We have over 1,500 patients exposed in our safety database, and we've shown clinical activity in multiple indications. We think really this approach to generating an IL-2-based drug is the way to go. We're really excited about REZPEG. Thank you. Your next question comes from the line of Jay Olson from OPCO. Your line is now open. Oh, hey, congrats on these landmark results, and thank you for providing this impressive update. We also had a question about the four excluded patients. Are there any steps that you can take to prevent these types of eligibility violations in future studies? And then also related to future clinical trials, any strategies you can use to mitigate early treatment discontinuation, recognizing that it may take some time for patients to see treatment benefits? And then finally, one of the KOLs commented that perhaps the benefits of REZPEG could be expanded to less severe patients. And we are wondering if you would expect treating patients earlier before they become severe could be an important treatment strategy that could result in deeper and more durable responses. Thank you. Thank you, Jay. You can bet, J.Z. and I have spent a lot of time with David, Jonathan, and Benji asking them exactly how to exclude these patients from a phase III clinical trial. They've given us a wealth of information. One is the timeframe by which somebody has actually been diagnosed. That is a simple review of the date. That should be very easy to comply with, and as long as the medical monitors have that very clearly laid out for them. The second is, though, making sure you enroll the right patients, and we can do a central review of the photographs of the patients' alopecia areata both at screening and before they're randomized to ensure these patients have stable alopecia areata as well. So we spent a lot of time talking about the phase III design and exactly how to ensure these patients are eliminated. One thing to be said, if we had our mITT patient population, even with a placebo effect of 11% in a phase III trial similar to Olumiant, we would have absolutely reached statistical significance. So in a much larger trial, the issues that we've actually seen will be diluted just by the fact of the sample size. The second, to talk about early treatment benefits, we've also spoken to Benji, Jonathan, and David about how they would approach this with their patients and that they feel like their patients, once we set expectations, would be willing to stay in the trial. And I will definitely turn it over to Benji to talk about this since he sees about 150 of these patients a year. David really is the one who's been pushing us to look in the moderate patient population. We're going to ask him to address that. Benji, you have so much hands-on experience with 150 patients you see every year. You're probably one of the highest dermatologists. You probably see more patients than the most, along with David and Jonathan. If you could please address how you would actually approach a patient who would want to enroll in the study given the kinetics. Yeah. I think that strategies about enrolling patients are obviously very important for the success of the trial. Fortunately, I actually think it's quite doable in this case. There are a number of different approaches, but I think one of the core issues here is something that actually was addressed by the phase II data, which is understanding the kinetics of the treatment. And so when patients are unaware of what to expect, it makes it very difficult for them to participate in a trial. Because let's say we fast-forward six months, they haven't seen hair regrowth. Does that mean they're on the placebo, that they're non-responding? The eagerness to get treated can be quite significant. Now, understanding actually the data that we have here, it actually helps provide understanding to the patient and investigators ultimately to have the conversation with patients to say, "This is what to expect." So you probably will not see results in the first three months with full hair regrowth, but that's okay because we expect the results to be later on. And part of the reason I think that it may seem trivial or almost straightforward, but part of the reason I know that's successful is because of the conversations I have with patients on essentially a daily basis with their expectations of treatments, including approved treatments. This is very similar to the conversations I have. And this is part of the education process. So just in brief, I routinely have patients who come to see me after having seen other dermatologists treated with medications like JAK inhibitors who come to me and say, "Hey, it didn't work." And as part of the discussion, we learned that they were not on treatment for long enough. And so simply understanding what to expect, a timeline can have a dramatic, and by the way, those patients then regrow hair under my care just because we give it more time. So understanding that perspective, I think, is a very, very crucial one. I do want to speak very briefly about the idea of earlier treatment and more moderate disease. So we now know across a number of trials that the sooner you treat alopecia areata, the better the outcomes, and the more mild disease, the more successful treatments are. And this is maybe thinking a little further down the line, but one could argue that there is an even larger need for treatments in that moderate to severe range because people are not willing to risk perceived safety issues for more moderate disease. And yet, these patients don't respond to local therapies and actually do need systemic therapies. And so I actually think that a treatment like this with these kinds of characteristics, safety, would be a tremendous benefit for that more moderate disease, including in terms of leading to better outcomes across the board with a long-term prognosis of this disease course. Thanks, Benji. And David, I know you too have been very enthusiastic about looking at the moderate population. And so I completely concur with Benji, and I suspect Jonathan will say the same thing. I do want to further delve into the other part of your question, though. Is how do you ensure successful phase III as somebody who really enjoys trial design? Well, one, there was no phase I study done here like there was for atopic dermatitis. And there have been other tested biologics for alopecia areata, which haven't had the same success. So now we know this works, and that affects what we convey to patients as well. There may have been others who were in the study that assumed, "Oh, I'm probably not on treatment," or, "It's not working after just a few months." But we now have that information that, again, you have to wait. Furthermore, we know also that the phase III is likely to have a crossover arm. So that also is very helpful at keeping patients in studies. And lastly, excluding some of the sites where maybe they have multiple studies at the same time that may compete, where sometimes sites are incentivized financially to move a patient from one study to another to capture larger revenue. So there's multiple reasons to be quite optimistic for the success of a phase III and to be more confident to have patients not only remain in the study and to really get quite good results. Thanks, David. Jonathan, do you have anything you want to add? I mean, I completely agree. I think really the key thing is as you move into a larger phase III program, you're going to be powered sufficiently to address any of these and buffer for all of that. And I think as much as this is a phase II-B study that we saw today, it's still a relatively small study. So once you go to that larger phase III program, you're sort of shielded or protected from any of these issues anyway. Yeah. Thanks, Jonathan. It's a great point. Thank you, David and Benji. Thank you. Your next question comes from the line of Roger Song with Jefferies. Your line is now open. Great. Can you hear me? Yes. Yes. Awesome. Great. Congrats for the data. It's really transformational. So a couple of questions. I mean, focus on the plateauing effect. It seems this is a key feature. You're not seeing the plateauing after 36 weeks. If my math is correct, with these three additional patients, you achieve placebo adjusted around 18% SALT 20. So can you just give us some context? How does that compare to low-dose Olumiant, even high-dose Olumiant, if we're thinking about additional seven patients potentially can achieve to SALT 20? And then maybe just a quick clarification question. In terms of ISR, I know this is a known AE for REZPEG, but it seems the placebo arm is also pretty high compared to the atopic dermatitis trials. What's the cost? I understand the placebo adjusted rate is pretty consistent. Thank you. Want to go, J.Z.? Yeah, sure. So I'll just sort of preface, but then I'll turn it over to our colleagues. I mean, your question was about sort of the comparison of the SALT 20 rate, and as you point out, the knowledge that we've already seen three people achieve a SALT 20 after week 36 and before week 52. And so kind of adding them into the numerator, yeah, you're right. We're right on, if not exceeding, the placebo adjusted rate for low-dose Olumiant. And then with the seven people ongoing, again, they're ongoing, right? So we can't comment about what could happen in the future. But you could envision the scenario where the majority of those people convert to SALT 20, and then we're exceeding the low-dose Olumiant bar for SALT 20. But what I'd like to do is, for me, I'm a different kind of a doctor, certainly not a dermatologist. I'd like to ask our colleagues to comment on that and that kind of long-term potential. Sometimes we've heard this sort of tortoise and the hare analogy about kind of how REZPEG might work. And that could be maybe one way to frame this. But I'd love to hear your thoughts. Yeah. And Jonathan, I think you've spoken a lot about this to us. So maybe you could start. Sure. The concept of speed sounds nice, but the reality is we have nothing right now in the field. We are really desperately lacking any clean biologics right now. And I think you contrast this to, let's say, atopic dermatitis and psoriasis, and you see very clearly who the winners are there in terms of the clean biologics. That is by patient preference as by provider preference. So first and foremost, this is a paradigm shift, right? Because this gives us that clean biologic to turn to as that first line systemic option and really shunts and changes the entire approach to say, "Well, now you've got that clean option to turn to without having to turn to the JAK inhibitor." So in a sense, the questions around, "Does it take a little longer?" become almost a moot point because the clinician is willing to wait there because he doesn't want to take that safety concern. The patient certainly doesn't want to take that safety concern. I think the clinicians will ultimately find ways of optimizing and how to navigate in that earlier period of time. And I think with proper counseling. And that's really a key thing that we saw here. Now that we understand the kinetics, we can give the patients the proper guidance in the clinical trials so that they're encouraged and they stay with it from a regulatory and trial perspective, but also from the real-world perspective. So we're armed now with information. And that information, I think, is going to become very helpful. But when you look at the curves, and I'm not a prophet, but when you look at the curves, you would expect the efficacy to actually overtake Olumiant with time. And that is something I think that becomes very important. Obviously, we won't know until we study it. That is the reason to study it in phase III and to go out to 52 weeks and potentially even beyond that. But my gut says, when looking at the data, we will see the efficacy overtake Olumiant too. The question is then, where is that ceiling on efficacy? Will we overtake Olumiant 4? Possibly, right? Again, we won't know until we study it. But I think there's a lot to be encouraged here about. Thank you, Jonathan. Benji or David, do you want to add anything? Go ahead. Sure. Sure. So I agree with everything that Jonathan said. I do want to offer a slightly different perspective because I think that part of the discussion here really needs to center around this is something I refer to, but really everyone has about the desire and appetite for a different strategic therapeutic approach. And so it is, I think, very nice to see that the efficacy matches at 36 weeks low-dose Olumiant, which is a very commonly used prescription among the kind of advanced approved therapies. I actually think that pegging the discussion about the efficacy here really is missing a big part of the dynamics of patient-prescriber discussions and decision-making about therapies, which is to say there is nothing about 36 weeks in the real world that is meaningful. That's no more meaningful than 52 weeks, 104 weeks, and so on. This is a chronic condition. And so looking at 36-week efficacy data is, in my mind, relatively meaningless. It's just an artifact of you need to decide on an endpoint in clinical trials. In fact, when we use treatments of other sorts, we look long-term what the effects are, not just how much hair is regrown, but how much of the hair is maintained, what the relapse rates are. And by the way, just not to go down that path, I think that's one of the strengths of a treatment that may have remissive effects. It's likely to maintain responses without flares, which just can't be overstated how important that is. And so I think that the fact is that if someone comes in with alopecia areata and you can prescribe a treatment that doesn't require monitoring, that doesn't require a discussion about the risks of very serious side effects, and that you know that it works without even looking at the numbers, it is going to be an absolute no-brainer for the vast majority of people to go down that route. And so yes, the efficacy data is actually quite encouraging, but I think it's almost secondary to the overall picture of just how potentially really game-changing this kind of drug is. Yeah. Thanks, Benji. And all three of you have shared with us. They're both the patients that you take share from who would go on a JAK inhibitor. And then you've also shared that you really broaden the absolute patient population with a biologic for those patients and even doctors alike who would never even prescribe a JAK inhibitor. And David, you've shared a lot with me about your colleagues and JAK inhibitors. Can you share this with those people on the call? Because I think it's really important. As Benji said, it's the safety, right? That's what people care about. And it's hard for people to judge how rare events are, but they just never want to do harm, especially serious harm. That's what really concerns other dermatologists. So even though it's rare, and by the way, JAK inhibitors are still going to be used in alopecia areata. However, as Benji is saying and Jonathan are saying, this will be used first, and it's the safety that's going to drive it. The efficacy is the secondary consideration for this condition, and in terms of the speed of onset, I agree. It's not as important here. Patients aren't staying awake at night due to their itch, so there's less urgency compared to other diseases like eczema, so again, I completely concur with my colleagues, and again, this I expect to be first-line therapy for the majority of patients. Yeah, and I think all three of you have shared with me both the serious safety concerns as well as the monitoring on treatment, but both are barriers to usage and that many of your colleagues won't even prescribe a JAK inhibitor for both of those two factors, so thank you. Thank you. Our next question comes from the line of Arthur He with H.C. Wainwright. Your line is now open. Go ahead. Hey, can you guys hear me? Yes. Hey, first of all, congrats to Howard and team. And it's really great data there. And Mary, welcome back. [audio distortion]. So just for the Nektar team, I had a quick question. So for the patient you excluded from the placebo arm, could you tell us more regarding the patient baseline in terms of the SALT score and how long these patients have been diagnosed before the randomization? Yes. Yeah. So the patient who was inappropriately enrolled had been diagnosed less than six months, roughly around five months when they came into the study. They were a SALT about 65 and pretty rapidly went down to a SALT 20. And so we can let our KOLs here address what happens to these patients who are newly diagnosed with very rapid hair loss and hair growth and the instability of the disease. So let me turn it over. David, we could start with you. Yeah, absolutely. When patients don't have stable disease, you can have a higher placebo rate and the spontaneous regrowth. And that's why it's routine in all our alopecia areata studies that we have certain criteria for enrollment, for inclusion and exclusion, and these patients are excluded. And the patient should have been. So following the protocol, again, you saw the results that it works. If you don't follow the protocol, you mess with the study. You can get high placebo rates. And the only reason why this is a factor here is because there were only 20 patients in the placebo arm. If you have a large study where you have several hundred in the placebo arm, this would be a blip on the screen, and it won't matter at all. But the key here is you don't want unstable patients in your alopecia areata studies. And this is not something that is exceptional to Nektar's study. This is routine in all alopecia areata studies. Thank you, David. And Jonathan? I completely agree. I mean, I think alopecia areata is an unstable disease as a general rule. In the early phases, when you first see a patient, depending on the severity, depending on their treatment journey, you really don't know where that's going to go. We know in certainly milder patchy alopecia cases, there's a lot of spontaneous regrowth. Sometimes we're hastening that. Sometimes even if you don't do anything, those sort of isolated patches can get better. I just say that as proof of concept that there's lots of ups and downs. When you start getting to the more severe disease, that's when you get more of that chronic persistent disease that just can be stably bad and just there's nothing. There's no hair regrowth. That's really the target population when you think about it. We discussed already the opportunity with a clean biologic to open it up to an even broader population. From the trial population, when you're trying to study that and you're trying to minimize placebo responses, there's a reason why we set these definitions in place because we want to know that we did it with the drug and that it wasn't happening spontaneously. It's as simple as that. Look, the protocol is meant to be followed, and it wasn't. To David's point, though, it's an N-of-1, right? That one case that affects the placebo. And in a small study, an N-of-1 can flip any of these sort of binary responses. If there were even 10 more patients in each arm, you wouldn't have seen the impacts of that single patient, right? And certainly, when you get to a larger power study, you look at the Olumiant studies, they had five times as many patients per treatment arm, right? So keep that in mind. When you have a larger powered study, you can buffer for all of this. So I think there's lessons learned, though. And I think we now know what to be sort of aiming for and watching for a little more with study monitoring in phase III. But I don't think that's any deterrent for us. I think that just gives us guidance on what to do in phase III. Yeah. Thanks, Jonathan. And Benji, any additional comments? Yeah. Yeah. I'll just add very briefly. So we know that in severe alopecia areata, outside the six-month range, spontaneous regrowth rates are extremely low. Clinically, anecdotally, epidemiologically, in all of the clinical trials thus far, we see the same trend. Placebo or spontaneous regrowth rates are quite low. And so when looking at the effects of the drug, we want to isolate the biological impact on the disease process. And therefore, we don't want the noise of someone who's fluctuating early on, which is specifically why, as everyone has said, we exclude those patients. That, by the way, is one of the reasons why I think the data are exciting is because we see a clear response that has to be driven by the biological effects of the drug. The curve of efficacy that we see with REZPEG from these data really can only be explained by the drug doing what we want. And so when I think about this as a phase II signal-seeking study to proof of concept to identify biological effects, I mean, that's exactly what we're doing because this patient aside, we're isolating the people where that's not going to happen on its own. Yeah. And Benji, can you comment? We showed you many more case studies than even we shared with the audience today. Can you comment from your clinical experience what you thought of these responses, especially some of these patients that sta rted out bald? Yeah. So again, my prior going into this before seeing any of the data on this, based on the mechanism Tregs really kind of upstream a lot of inflammatory pathways, is that this would not be a very rapid treatment, that the responses were going to be after several months, which is, if anything, I think these results are probably a little more rapid even than I would have expected, which is quite encouraging. I think that when we look case by case, it's probably true. And again, let's keep in mind that this is a preliminary study of sorts, that the effects that we're seeing numerically may be underestimating actually what's happening from a clinical perspective. Because I think, again, many of the lessons learned in terms of enrollment, the design, and so on are going to also apply to grading and scoring. When we reviewed some of the individual cases, I think some of the patients actually were more severe than certainly I would have scored them at baseline by quite a large amount in some cases, or at least a reasonable amount. I think that that happened a number of times. I actually saw no instances of the reverse where someone was being kind of under where the effect was under or rather overstated, if anything, the effects were understated. Again, these are not responses that we see in the cases that happen to people with stable severe disease. We just really don't see that. That really demonstrates that this drug is having an effect on the underlying disease pathology that leads to hair loss and with subsequent treatment, hair regrowth. Yeah. Thanks so much for commenting on that, Benji, because the steering committee unanimously agreed with you that there was probably an underestimation of the true effect of REZPEG given that the baseline photos from your experience seem to underrepresent the severity of the disease, meaning the baseline SALT score was probably lower than it actually is. Thank you very much. Thank you. Your next question comes from the line of Samantha Semenkow with Citi. Your line is now open. Hi. Good morning, everyone. Thanks for taking the question. And congratulations on this data. I do want to continue the conversation on the lack of plateauing that we're seeing here by week 36. This is similar to what we've seen in the atopic dermatitis trial at week 16. So I'm curious for the physicians that treat both diseases, does this increase your confidence in REZPEG across both diseases? Just based on the data sets that we have, how should we think about what the time on therapy is that is needed to reach maximal benefits? And maybe we could talk about both indications and any expectations into perhaps what we could see in atopic dermatitis with longer treatment. Thanks very much. Thank you, Samantha. And let's have Jonathan start as our lead author of the atopic dermatitis presentation at [audio distortion] this year. Sure. Thanks. So there were a few questions there. I hope I don't miss them. But just to start with the first one, from my perspective, I certainly didn't have any doubts. And I don't think we had any doubts now that REZPEG works well in atopic dermatitis. It's always nice to have confirmatory data in other diseases. I think, again, the nerdy immunologist in me is we've been talking about the Treg hypothesis for 20+ years. And it's always been this discussion of causation versus correlation. And is it real? Is it not? So this just really reinforces that the Treg hypothesis is real and that if you selectively upregulate Tregs, you can improve a disease. I mean, I think that is a super cool thing. And then the question then becomes, okay, well, what are the next indications? Because there are plenty of other T cell-mediated disorders out there that we could consider to go after. So I think that has its own ramifications from a lifecycle management perspective. But at least within AD and alopecia areata, I think it just further supports the efficacy in both diseases sort of simultaneously. Of note, there is a subset of patients with alopecia areata who have atopic dermatitis and vice versa. So the idea that you have a drug that would, quote-unquote, "kill two birds with one stone" is also very cool. It's often been the JAK inhibitors that have sort of served a little bit of that niche before. And now we don't have to turn to JAK inhibitors. Now we have a clean biologic that can serve that role. So I think that that's an important consideration, although that overlap is not necessarily the largest part of the market by any stretch. So that's sort of my perspective on the biologic efficacy. And I apologize, but I forgot the rest of the questions. It was about time on therapy. Oh, time on therapy. And does this thing, yeah, increase confidence across indications, seeing deepening now into? Yes. Yeah. And I think the asymptotic comments about plateau. And maybe you could explain to people what that means too, Jonathan. Sure. Sure. So with every disease and with every drug, the kinetics curves can and should look different, right? It depends on the mechanism. It depends on a lot of different things. When you think about atopic dermatitis, we've seen with a number of the biologics that the longer you're on drug, the more you get stable efficacy, the better you get. So some of the psoriasis biologic curves look a little different in that respect. And I think here what we're seeing is something similar, both in AD and in alopecia areata. The idea that the longer you're on drug, the better it gets in terms of stabilizing the responses, in terms of deepening the responses, in terms of more reliable responses, right? Now, there's patients who may have previously, not in the first 36 weeks, maybe they didn't really have so much hair growth. And we're starting to see, as you saw some of those cases already, that some switch is turning on even after 36 weeks where they're gaining that efficacy. So those are sort of three different considerations about why we'd want to have patients on drug. But for those patients who may not have this light switch flipped at whatever week 16, I'm just random time point, and all of a sudden, the hair just turns on and fully regrows, it doesn't work that way, right? Patients have a sort of slow and steady regrowth. And you would potentially worry if there's sort of that slow growth and then it halts, right? And they just can't get past a certain point of regrowth. But when you see that curve just continuing to improve in its efficacy without flattening out, what that tells us is just keep going and you're going to get more of that slow and steady regrowth. And then on top of that, there's a subset of patients where, again, you saw these cases. There really wasn't much growth early on at all. And for whatever reasons, biologically, they just start to turn on later on. And so now that would be an argument, okay, just keep it going. And we would expect many patients who are, quote, "non-responders" earlier to become responders, or many patients who are partial responders to just continue to march along and get further response. I think these are both very clinically intuitive sort of scenarios and treatment journeys. And I think the dermatologists will be able to work with this very easily. Thank you. David, I know you serve on our steering committee for both atopic dermatitis and alopecia areata. If you want to add anything to what Jonathan eloquently just stated? Yeah. As usual, I agree with Jonathan. And look, I'm optimistic that there will be that deepening and sustained response. And we'll know soon enough within a few months from the 52-week data. So I do expect those numbers to go up. To be fair, they do increase somewhat in the JAK inhibitor trial. So again, they're going to increase somewhat in the REZPEG study. The question is, will they increase more so than they do for the JAK inhibitor study? And that's what we're really hoping for. And that's what Jonathan's saying. Also, one thing that I just want to emphasize as well is the fact that we're seeing regrowth of eyebrows and eyelashes, which is really challenging, is also extremely meaningful to me and very telling. That also, some of the studies show that eyebrow and eyelashes can regrow a little bit earlier as well. So the fact that we're seeing that also has me more optimistic that with more treatment, again, we'll see more responders on the scalp as well. So again, there's a lot of reasons to be optimistic about this overall. But looking at the very big picture, whether it's a little bit more effective or not is not what's ultimately going to determine the success. It's the safety. And the fact that it works and has that safety profile and minimal monitoring is what makes this the first-line option. Yeah. Thank you, David, for underscoring that repeatedly. And you can't state it enough because when I've met with all three of you, you tell me you have colleagues who will never prescribe a JAK inhibitor specifically for that reason alone. It's pretty remarkable. So thank you for emphasizing that critical point. Thank you. Your next question comes from the line of Mayank Mamtani with B. Riley Securities. Your line is now open. Yes. Good morning, team. Thanks for taking our questions. And congrats on very impressive results. Just a few clarifying questions. So on the waterfall chart, you do have some super responder placebo patients. So maybe just touch on how those responders differ from the four that you're excluding in the mITT. And I also noticed in the placebo cohort, you have a higher number of patients from Poland. Any significance of that as you think about your next phase III study? And on that note, any gating steps as you also prepare for your end of phase II separate, I assume, for alopecia? And maybe comment on what atopic derm FDA correspondence also operationally helps as you think about this alopecia-specific discussion. And J.Z., you're big in biomarkers. Any early evidence that you're seeing Th1, Th17-mediated mechanism that allows us to understand responders versus non-responders early on from this alopecia data set would also be helpful. Thank you. Thank you. I can just address Poland and the placebo first. One of the patients with lack of stable disease was enrolled in Poland. And we did have two clinical sites that were recommended to us by the CRO that did have a high dropout rate. Six out of six patients discontinued early. Another site, eight patients were enrolled and six dropped out. And so we do agree with you that you have to be very careful about the clinical trial sites that you allow to participate in your studies. And that is certainly a lesson learned. And we've spoken to Benji, Jonathan, David extensively about the selection of sites moving forward into our phase III. We've also spoken to Benji, Jonathan, and David about the specific placebo patient who responded. And we've had a long conversation about that, which I'll let them weigh in on. But before we do, Jonathan Zalevsky, do you want to make any additional comments about biomarkers or the waterfall plot before we pass? Sure. No, thank you, Mary. And thank you, Mayank, for the question. Since this was really a first signal-seeking exploratory study, we didn't do a lot of additional collections in this study. We were really looking for translating the science that was known and published before we moved into this. So that will be the subject of future studies, Mayank, in alopecia, where we can tease apart some of those underlying elements. For example, we know interferon gamma is a big contributor and driver of this disease. And addressing more of that pathway with a Treg mechanism, which would do it very differently than a JAK mechanism would. So that will be the subject of our future activities in this study. But I think, yeah, I think just getting back to the placebo question is critical for the there was one included patient that had a response. I mean, we see that trends quite similarly with other studies. But I'll maybe turn it over to you, maybe David first, to just sort of comment. I know you've reviewed all of the case studies and other things, including that one included patient. Yeah. So first of all, this sometimes happens where you can have patients who have spontaneous regrowth. It's a very, very low rate. But it does happen in these studies. And that's why we run studies with phase IIIs will have hundreds of patients in it. So I don't think there's anything to be concerned about. The fact that there are some patients that have a response, this is what we expect. And the fact that you're seeing about a 30% mean decrease should give us very, very high confidence that a phase III will be successful. This shouldn't even be close. Thanks, David. Thank you. And your final question comes from the line of Andy Hsieh with William Blair. Your line is now open. Great. Thank you so much. So I'm looking at the SALT score reduction curve. And there's a slide basically comparing that with Olumiant. And I guess the initial observation is that the curve is inversed. Obviously, with REZPEG, you do have the MOA, PK/PD to explain that effect. But I'm just curious if either Nektar or KOLs can comment on the shape of the placebo. Why is that looking a little bit different compared to the JAK studies? Thank you. Jonathan, do you want to comment on it? When we look at the mITT with four patients removed, I don't know if. Maybe let's put up slide 15. Yeah. You can see that there's a slight increase in the placebo effect before it ends up being about what you see in the phase III studies. Sorry, is that targeted to me or? Yeah, I'm going to ask you, Jonathan. Oh, yeah, which Jonathan? Yeah. I'm sorry, Jonathan Silverberg. Oh, that's perfect. Yeah. I mean, you love to talk about statistics, Jonathan. I do love to talk about statistics. I think, well, okay. So. Can we put up the slide? Yeah. Thank you. Yeah. I mean, first and foremost, you could see also the placebo arm in the REZPEG study is a little bit more. Yeah. So when you look at the placebo arm, and what you see versus, let's say, the bari studies, there are a few things that should jump out at you. One, wider confidence intervals, a little bit more unstable. And that is a sample size issue, period. And I don't think there's anything more to it than that. You compare sample size, you're literally more than five times, almost six times the sample size per study arm in the bari study compared to REZPEG. And so that gives you a more stable, smooth curve with a tighter confidence interval. I expect that you're going to end up seeing something that is more akin to the Olumiant placebo response once you move into phase III. So it's nothing that stands out to me necessarily. I think it's just, again, an artifact of sample size. What I think is impressive, just as a related aside, is that despite the small sample size, you actually have such clean, consistent curves on the REZPEG side of things and how smooth they are. And to me, that's actually reassuring. I sort of alluded to that in my opening comments, but that actually reassures me that we have a good sense of effect size to help inform power calculations for phase III. Thanks. Thank you, Jonathan. The other point, which I mentioned earlier, Jonathan Silverberg asked us when he immediately saw the mITT data, he said, "Well, if this were a clinical trial the size of baricitinib's phase III, I suspect we would have reached statistical significance." But Mary and J.Z., go back.