Good day, and thank you for standing by. Welcome to the Nektar Therapeutics first quarter 2024 financial results conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Vivian Wu. Please go ahead. Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. With us on the call are Howard Robin, our President and Chief Executive Officer, Dr. Jonathan Zalevsky, our Chief Research and Development Officer, Dr. Mary Tagliaferri, our Chief Medical Officer, and Jennifer Ruddock, our Chief Business Officer. Unfortunately, Sandra Gardiner, our Acting Chief Financial Officer, was not able to make it on today's call due to an unexpected family emergency. 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 drug candidates and research programs, the timing of the initiation of clinical studies, and the availability of clinical data for drug candidates; the timing and plans for future clinical data presentations; the formation, future development plans, or success of our collaboration agreements; the expectations following our corporate restructuring and reorganization; financial guidance; and certain 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. Our actual results may differ materially from these statements. Important risks and uncertainties are set forth in our Form 10-K that was filed on March 5, 2024, which is available at sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of information, future developments, or otherwise. A webcast of this call will be available on the IR page of Nektar's website at nektar.com. Before turning over the call to Howard, I would like to note that our team is dialing in from different locations and that Howard will be moderating the Q&A session for our team so we can avoid technical issues during the session. We appreciate your patience. With that said, I would like to hand the call over to our President and CEO, Howard Robin. Howard? Thank you, Vivian, and thank you all for joining us today. We've begun 2024 with positive momentum as we continue to build a best-in-class pipeline focused on immunology and inflammation. One of our key goals is to address the underlying deficiency in regulatory T cells, which underlie a range of serious immune disorders. We have several key immunology targets and first-in-class mechanisms in our pipeline, including our lead program, REZPEG, as well as the new TNFR2 agonist, NKTR-0165, both of which target immune-resolving pathways. In the first quarter, we continued to make significant advancements with our REZPEG program. As you know, we're evaluating REZPEG in a phase 2b study in moderate to severe atopic dermatitis, which started last year, and the study is currently enrolling patients worldwide. I'm pleased to report today that the study enrollment is on track to report top-line data from the study's 16-week induction period in the first half of 2025. There are approximately 30 million people in the U.S. alone living with atopic dermatitis, and half of these patients are diagnosed with moderate to severe disease. Biologic treatments in atopic dermatitis represent a multibillion-dollar market that continues to grow, and we're excited that REZPEG could become a highly differentiated treatment for atopic dermatitis, a disease that still has a high unmet need for safety and durable treatment options. We believe REZPEG has the potential to be a significant advancement in the treatment of atopic dermatitis. The new and corrected data from the phase 1b study we reported at the EADV conference last year showed a dramatic drop of 83% in EASI scores over 12 weeks of treatment. Notably, the study also showed that REZPEG resulted in durable responses 36 weeks after treatment ended, opening up the potential for REZPEG to have an immunomodulatory effect. This past quarter, we initiated our second phase 2B study of REZPEG in patients with severe to very severe alopecia areata. We believe there is a significant opportunity for REZPEG to help people with this devastating disease. Nearly seven million people in the U.S. alone have or will develop alopecia areata. This disorder significantly affects the quality of life for patients, and the currently available therapies are not durable, have high relapse rates, and carry significant safety risks. Therefore, there's an urgent unmet medical need for new therapies. Enrollment opened in March for the phase 2B alopecia areata study to evaluate REZPEG over a 36-week induction period. Jonathan Zalevsky will talk more about this program later on the call. Enrollment is on track for this study, and we expect to report top-line results in the first half of 2025. In addition, we're advancing NKTR-0165, our novel TNFR2 agonist antibody. TNFR2 has been shown to potentiate the suppressive effects and overall functional properties of Tregs. This program is built on what we've learned through our deep experience with REZPEG and the Tregs field and represents a promising first-in-class differentiated mechanism for multiple sclerosis, ulcerative colitis, and a range of other autoimmune diseases. We're currently conducting IND-enabling studies with the goal of submitting an IND in mid-2025. I'm pleased to announce that our preclinical data has been selected for a presentation at EULAR, and we're looking forward to presenting the first data on this program. Moving to NKTR-255, our IL-15 program in oncology, we're continuing our clinical work with our partners, and we expect data from some of these partners this year. Consistent with our strategic focus in immunology and inflammation moving forward, we're continuing to evaluate strategic partnership opportunities for this program. Finally, Nektar is in a strong financial position with a cash runway that extends well into the third quarter of 2026. I'm very proud of our team at Nektar, and we are laser-focused on executing the development plans for REZPEG in order to achieve value-enhancing data milestones next year. With that, I'll hand the call over to J.Z. for an R&D discussion. J.Z.? Thank you, Howard. Beginning with REZPEG, this program is the most advanced IL-2 Treg mechanism in the field. In the setting of atopic dermatitis, there are three important issues that patients with this disease continue to face. First, there is a need for more efficacy, a greater magnitude of response, and rapid onset of treatment. For example, only about half of patients treated with IL-13-based biologics achieve a meaningful clinical benefit. Second, patients lack durable responses and therapy-free remission. Once current therapies are discontinued, patients rebound rapidly. Third, treatments with tolerable long-term safety profiles are lacking. This is especially important given the chronic nature of the disease and the need for continuous dosing. We believe there are major opportunities in this disease state that REZPEG could potentially address. In our phase 1b data in atopic dermatitis, REZPEG demonstrated dose-dependent efficacy and encouraging durability seen long after the patients completed the 12-week induction period. In fact, for both patient-reported outcomes and physician-assessed endpoints, we observed the same trend: rapid onset of effect, dose dependence, and long durability of control. Additionally, REZPEG was well tolerated, and treatment with REZPEG did not induce antidrug antibodies in patients, which has been reported with some examples in the IL-2 mutein class. We are looking forward to publishing in a peer-reviewed journal this year new translational biomarker data from the study, along with the clinical and safety data from atopic dermatitis and psoriasis. The rapid onset of action and the type of extended disease control after the end of dosing rivals or outperforms that of dupilumab or JAK inhibitors. These promising data have us in KOLs very enthusiastic about the potential for long-lasting responses and infrequent maintenance dosing with REZPEG in atopic dermatitis. Enrollment is progressing on track in our phase 2b study of REZPEG in biologic-naïve atopic dermatitis patients. Our goal is to enroll roughly 400 patients with three different regimens of REZPEG versus placebo, evaluated over a 16-week induction period. After the induction period, patients that meet a threshold to advance from induction to maintenance will be re-randomized into one of two maintenance regimens at different dosages at either once a month or once every three months dosing schedules. We expect initial data in the first half of 2025. Now, moving to alopecia areata, we believe REZPEG has strong scientific rationale in this indication. Alopecia areata is also a disease of the skin where your immune system starts to attack the hair follicles, weakening the ability of stem cells to grow hair. With prolonged immune attack, it causes the hair follicle to release the hair altogether, resulting in baldness. Biologically speaking, REZPEG, through its central pathway of Treg rescue, is uniquely poised to address the diversity of immunopathology, providing broad potential for targeting multiple dermal diseases, including alopecia areata. Specifically, alopecia areata is a breakdown of immune privilege in the hair follicle. So what does this mean, exactly? Well, normal hair follicles exist in the state of immune privilege. So in other words, there are no immune cells, no MHC expression, and basically no immune system components inside the follicle. We know this exclusion of the immune system is needed to maintain healthy, long-lived, and continuously functioning stem cells to grow hair during our lifespan. In people with alopecia areata, there is a breakdown of the immune privilege in the hair follicle: infiltration of the immune system, inflammation, and all this leads to hair loss and eventually complete baldness. Preclinical studies in vitro and in mice implanted with human alopecia skin samples have shown that Tregs are essential for restoring and maintaining immune privilege and thus are a novel therapeutic strategy for the treatment of this disease. Consequently, we believe the Tregs mechanism of REZPEG can restore immune privilege and could provide durable disease control, which would be game-changing in this indication. Alopecia areata JAK inhibitors are the only agents approved in this field, and it is a lifelong treatment. With JAK inhibitors, it can take a patient anywhere from 6-12 months to grow hair. Once a patient stops taking a JAK inhibitor, which may happen for a variety of reasons such as toxicity, their hair falls out again rapidly. There is a high unmet need in this patient population for tolerable treatment options that provide durable responses. For these reasons, we believe there's an opportunity for REZPEG to become a novel biologic therapy in alopecia areata. We are well underway with enrolling patients into the phase 2b study of REZPEG in alopecia areata. This study plans to recruit roughly 80 patients with severe to very severe disease that will be randomized to REZPEG or placebo. Patients will be treated for a period of 36 weeks and observed up to 60 weeks in total. Our primary endpoint for this study is mean% improvement in SALT, or the Severity of Alopecia Tool, at week 36. We will also be looking at a number of other secondary endpoints, including proportion of patients that were observed to have varying degrees of improvement in SALT score. We expect to have top-line data in the first half of 2025. Now, turning to NKTR-0165, our TNFR2 agonist antibody. TNFR2 is highly expressed on Tregs, myeloid suppressor cells, regulatory B cells, neuronal cells, and others, and TNFR2 agonism has been shown to potentiate the effector functions, suppressive functions, and maintenance of lineage stability of Tregs, especially in non-lymphoid tissue compartments. If TNFR2 is absent, the phenotypic effect is autoimmunity and other genetic conditions that resemble FOXP3 loss of function. In contrast, its presence and activation of its signaling has been associated with immunoregulatory function and protective effects for multiple cell populations and tissues in the body. The TNFR2 agonist program is built upon many years of Tregs experience that we've gained from studying REZPEG. TNFR2 is the most abundant TNF superfamily member expressed on Tregs and the key driver of NF-κB signaling in those cells, which is why we are very excited about this program and target. In our program, we collaborated with an AI-based antibody engineering company to screen a wide diversity of TNFR2 selective binding antibodies for novel modes of TNFR2 agonism. We are very excited with the unique and differentiated profile of the antibodies that we have discovered, and we are rapidly advancing these into the clinic. We anticipate our IND submission for this program in the middle of next year. Examples of indications that could be addressed by TNFR2 agonism include multiple sclerosis, mucosal immunology conditions such as ulcerative colitis of the GI or other oral mucosal diseases, and even dermal autoimmune diseases like vitiligo. As Howard mentioned, data from our preclinical research of this program has been selected for poster presentation at EULAR. This will be the first look at this novel, therapeutically active anti-TNFR2 agonist antibody, and we're looking forward to presenting these data. There is growing interest for a novel, selective TNFR2 agonist like NKTR-0165, and as we move forward with our IND-enabling studies, we will continue to be open to the opportunity of working with companies that have interest in these areas to strategize on the best path forward. And finally, turning to our IL-15-based oncology program, NKTR-255. We believe the IL-15-based mechanism of action has promising potential as a combination agent with cell therapies and other mechanisms such as checkpoint inhibitors. We are exploring the best partnering paths for continued development for this drug candidate. We are completing our Nektar-sponsored trial combining NKTR-255 with approved CD19 CAR-Ts, BREYANZI and YESCARTA, for treatment of patients with large B-cell lymphoma. A separate investigator-sponsored trial of Fred Hutch is also evaluating the combination of NKTR-255 and BREYANZI, and we plan on presenting data from this ongoing study at a medical meeting later this year. We continue to collaborate with Abel Zeta, a leading cell therapy company, to evaluate NKTR-255 in combination with their tumor-infiltrating lymphocytes, or TILs, TIL therapy in an ongoing phase 1 clinical trial in patients with advanced non-small cell lung cancer who do not respond to anti-PD-1 therapy. Lastly, we are continuing to work with our partner, Merck KGaA, in the phase 2 JAVELIN Bladder Medley study, evaluating NKTR-255 in combination with BAVENCIO, and expect to report interim data, including PFS, later this year. With that, I will turn the call over to Jennifer for a review of our financial guidance. Jennifer? Thank you, Jay Olson, and good afternoon, everyone. We ended the quarter with $326 million in cash and investments, with no debt on our balance sheet. Our financial position remains strong, and we still plan to end 2024 with $200 million-$225 million in cash and investments. This cash guidance includes a $30 million private placement of pre-funded warrants completed in Q1 and a $15 million cash payment from an amendment of the 2020 agreement with HealthCare Royalty, also completed in Q1. Our cash runway now extends well into the third quarter of 2026, which will take us through several key data milestones, including, of course, the top-line data from the Phase 2 REZPEG studies. I'll now briefly review our quarterly financials and reiterate our financial guidance for 2024. Our revenue was $21.6 million for the first quarter of 2024. We still expect our revenue for the full year to be $75 million-$85 million, which includes $55 million-$65 million in non-cash royalties and $20 million-$25 million in product sales. R&D expense for the first quarter of 2024 was $27.4 million, and we still anticipate full-year R&D expense to range between $120 million-$130 million. G&A expense in Q1 was $20.1 million. We continue to expect G&A expense for the full year to be $70 million-$75 million. Our 2024 non-cash interest expense guidance also remains unchanged and is expected to be $20 million-$25 million. Our net loss for the first quarter of 2024 was $36.8 million, or $0.19 per share. I will note that the loss per share reflects an increase in weighted average shares outstanding during the first quarter as compared to a year ago. The increase is primarily related to the effect of the PIPE financing in March and is partially offset by the effect of the shares we repurchased from Bristol-Myers in February. Both of these items will be fully reflected in the calculation of weighted outstanding shares at the end of the second quarter. As I mentioned earlier, we still plan to end 2024 with $200 million-$225 million in cash and a runway that extends well into the third quarter of 2026. With that, we'll now open the call for questions. Crystal? Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question will come from Jay Olson from Oppenheimer. Your line is open. Well, hey, congrats on all the progress, and thanks for taking the questions. Can you talk about the enrollment progress for REZPEG in both AD and AAA, and how is the enrollment tracking with your internal projections? Yeah, I'll let Mary answer that in detail. Our enrollment is going perfectly according to plan, but I'll let Mary explain it in a little more detail. Go ahead, Mary. Thanks, Howard, and thank you, Jay, for the question. So just to remind you, in October of last year, we started our phase 2B study where we plan to enroll 400 patients with moderate to severe atopic dermatitis, and these patients are all biologic naive. As both Howard and Zalevsky mentioned on this call, we are absolutely on track to have our top-line data from the 16-week induction period in the first half of 2025. The study is enrolling as expected, and the trial is currently open for enrollment in the United States, Canada, Australia, and Europe. The feedback we've received from our investigators is that they're very excited to evaluate REZPEG given the novel mechanism of action to boost Tregs. The investigators also liked the compelling data in atopic dermatitis that was presented by Dr. Jonathan Zalevsky at EADV last year. As Howard and Jay have mentioned, the phase 1b showed that REZPEG had the 83% reduction in mean percent change in EASI, and with just a small sample size, we reached statistical significance compared to placebo. So the doctors are also very excited about the powerful efficacy. They, as practitioners, are very familiar with the real-world evidence showing the lack of durability when they treat their patients with Dupixent. And it's shown in the literature that 79% of patients that discontinue Dupi lose their disease control after an average of four months off treatment. So the practicing dermatologists greatly appreciate the remittive effect that Jay was talking about and the durability of responses that we saw off treatment for nine months in the patients that were dosed in the phase 1b. I'll just say finally that the staff at these sites, as well as the investigators, also really appreciate that REZPEG has a very well-tolerated safety profile. So moving over to alopecia, it was in March when we started the phase 2b trial. As Jay Olson mentioned, we're going to evaluate two different doses versus placebo with the SALT scores as the primary efficacy endpoint. The trial is going to be open at roughly 28 sites in the U.S., Canada, and Poland. Again, we are absolutely on track with our enrollment to allow us to have data in the first half of 2025. Thank you so much. That's super helpful. Really appreciate the additional color on the promising efficacy of REZPEG, especially in atopic dermatitis. Maybe just if I could follow up on your comments about the safety, since there was a competitor's phase 2 atopic derm study that was recently closed following a clinical hold, can you just comment on any feedback you're getting from the DSM-B on the safety of REZPEG and atopic derm? Sure. So we have now conducted 9 clinical trials in the REZPEG program, and there are 592 patients who've been exposed to REZPEG to date. There were about 150 patients in the program who were randomized to the placebo in our trials. When we received all the data back from Lilly from these completed trials, our various Stuart biostatisticians and drug safety team created pooled safety tables so we could more closely review the safety profile of REZPEG. We plan to publish these data, but from a very high level, there are some really important key takeaways from the integrated safety data. The first is the most common side effect we see is injection site reactions. These tend to be mild to moderate, and they're seen mostly in the first or second cycles, and their frequency and duration wane over time. But most importantly, REZPEG is not a classic immunosuppressant, and we were very pleased to see there were no increased risks for infections. So we didn't see any increased cases of COVID on the REZPEG arms versus placebo. We don't see any increased risk for reactivation of herpes, either herpes simplex or herpes zoster. We don't see conjunctivitis as an increased risk on REZPEG, and we don't see the facial erythema, red face, or arthralgia. Now, getting to the other hepatotoxicity issue that you're talking about with the other agent of great importance, we do not see any increased risk for hepatotoxicity or AST or ALT increases. We do see that some patients have increases in eosinophilia, but no cases of any kind of symptomatic eosinophilia or tissue damage or organ involvement. Then just finally, we saw that there was a higher incidence of severe treatment emergent AEs and serious AEs only in the placebo group when we compared to REZPEG. We're very pleased by the safety profile, and again, our investigators are very happy to move this compound forward in clinical testing given the well-tolerated safety profile for a biologic and, again, no evidence of increased risk for hepatotoxicity. Thanks for pointing that out, Jay. Oh, thank you so much for the comprehensive overview of REZPEG's safety. If I could maybe sneak in one more question on the TNFR2 program, can you please talk about the preclinical data that you're expecting later this year and the strategy behind clinical development and prioritizing the different indications you're thinking of? Yeah, sure. Hey, Jay, this is J.Z. So yeah, so EULAR is in June, right? So yeah, we'll be presenting in roughly a month, and it's in Vienna this year. And so the data that we'll be presenting is we'll present work around the discovery of the antibody. We took a kind of a novel approach in how we identified agonists. So part of that definitely came from the AI-based computational engineering, and the other part was how we screened for the agonism. So that'll be one element of the presentation. That defines the discovery of antibody specificities and epitopes. And then we've, of course, turned those into preclinical development candidates. So that kind of data is presented there as well. So there'll be binding data, specificity data, cell signaling data, changes in the kind of architecture of the cells that you expect to see when you agonize TNFR2, and also some animal data showing biological activity and clinical efficacy in some animal models. So it'll be, for us, an important milestone is the first preclinical presentation of the work that we've been doing in the program in a public forum under the guise of a very important and critical medical meeting, as EULAR is a very, very large conference. In terms of indications, one of the things that's really unique about TNF2 is that as regulatory T cells move further and further away from either the thymus or the blood or the secondary lymphoid organs like the lymph nodes, the spleen, and so on, as they move into non-lymphoid tissue, they become much more dependent on an NF-κB signal and on actions of ligands for TNF2 as a key transducer of NF-κB. We're looking at other indications, and that's why, for example, mucosal immunology kinds of conditions are very high on our list. We know that in the mucosa, Tregs have a completely different cytokine environment that they're exposed to. There's very low IL-2 in those kind of environments, right? So they need a different kind of a signal. So ulcerative colitis and indications that impact both the lower or the upper mucosa are ones that we're prioritizing. And then we also know that in the setting of CNS, particularly around the role of myelin and demyelination and the role that TNFR2 plays in controlling some of that biology, which has been really nicely shown in animal preclinical models and mice, that that's another reason why multiple sclerosis also is a high indication for us. So that's just a flavor of how we're thinking about the program. But certainly, the two really go together, and they're highly complementary. And they kind of, between REZPEG and NKTR-0165, they kind of hit the two main biological axes of Treg biology. Sounds great. Look forward to that. Thanks again for taking all the questions and congrats on all the progress. Thanks, Jay. Thank you. Our next question will come from Roger Song from Jefferies. Your line is open. Great. Thanks for the update and taking all questions. Maybe just quick one regarding the REZPEG, the next steps after the phase 2b results, understanding you need to follow them a bit longer. But at the top line, what will be your next steps plan for those two indications? Thank you. Okay, well, I'll have Mary answer that. But clearly, we said we'd have data from the initial 16-week induction period by first half of next year, and then, of course, we'll go into looking at the durability of the response. But I will let Mary expand on that. Yep. Thank you, Howard, and thank you, Roger. So lucky for us, the pathway to approval for an agent that you're developing for atopic dermatitis as well as alopecia is very clear. So for atopic dermatitis, should our phase 2B trial read out as positive and we show a statistically significant benefit on the EASI score, then we would start planning for the phase 3 program. And in the phase 3 program, typically, you have either one or two doses of your drug versus placebo. Also, the primary efficacy endpoint in these two monotherapy trials versus placebo is the 16-week. Some other agents look at a 24-week induction period. And for the FDA, the primary efficacy endpoint is the VIGA, and in Europe, it's a co-primary endpoint of VIGA plus the EASI 75. In addition to those two phase 3 monotherapy trials, you typically do a combination trial with topical corticosteroids versus just topical corticosteroids alone, and that is the phase 3 program for atopic dermatitis. These trials are pretty easy to enroll to. It generally takes about a year to enroll to those studies. In addition to the efficacy, you need roughly about 600 patients that have been exposed to REZPEG at your highest dose for 12 months. And then in terms of alopecia areata, it would be two phase 3 trials, and it would be REZPEG versus placebo. Again, the induction period is a little bit longer than you see in atopic dermatitis because it takes longer to grow hair, so the induction period tends to be about 36 weeks. There's obviously not a combination trial that would be run. In contrast, atopic dermatitis that requires two phase 3 trials, in alopecia areata, it would be two. Great. Thanks for the detail. Then maybe if you can comment on your ongoing litigation with Eli Lilly for your REZPEG and any kind of updates from that end? Thank you. Sure. Look, as you know, the court ordered us to go to mediation with Lilly, and that's actually scheduled for next week. We're not going to comment on the results of this. We'll comment when we reach a solution with Lilly, but we will be mediating with them. They were clearly responsible for an egregious error that changed the dynamics of REZPEG. And clearly, if you look at the original data and then you look at the corrected data, REZPEG seems to function very, very well in atopic dermatitis, and it appears to be highly competitive, very different from their initial calculations. And they filed a counterclaim, which, of course, has very little merits behind it. And certainly, we don't expect that to be valued by the court, nor do we expect that we will owe Lilly any money. Not at all. I think this will sort itself out over the coming year. I can only tell you that the judge did not dismiss our case against Lilly and ordered us into mediation. We'll see how that goes. Excellent. Yeah, I look forward to that. Thank you. Thank you. Our next question will come from Jessica Fye from JP Morgan. Your line is open. Hey, this is Nick Alford, Jess. Thanks for taking our questions. Maybe just a quick one in revisiting the design of REZPEG. I understand the PEG conjugation imparts kind of a differential bias for IL-2 or alpha versus beta, but can you remind me exactly where on the IL-2 molecule the PEG is placed to impart that bias binding? Jay, you want to take that? Yeah. Hey, Nick. Yeah, so we've not shared that level of detail. We have published in our first manuscript in the Journal of Translational Autoimmunity a lot of information about the design of REZPEG, but yeah, we've not shared which amino acids, for example, are pegylated. What I can tell you is that we have a lot of experience in designing these kind of molecules, and this kind of a molecule in REZPEG is very similar to some of the original kind of foundational molecules like PEGASYS or Neulasta that we made with many of our partners over the decades. And then in regards to how it works, right, those biological effects from the pegylation, they impart the right kind of receptor occupancy. They impart the right kind of duration of signaling. And that's what gives REZPEG this continuous ability to renew regulatory T cells as you continuously dose it. We have data dosing people for 3 months, for 6 months, with the maintenance of that kind of pharmacodynamic effect. That's the goal, right, of that treatment. Makes sense. And maybe just a quick. That makes sense. Yep, that makes sense. Maybe just a quick follow-up too, building on that. I know there's obviously clinical data. There's in human data. But just understanding a bit more, I know there were some observations of NK cell activation higher doses in another earlier models. Have you seen any instances of that happening in the clinic and at the doses that you're testing, and how would that manifest if so, either AD or alopecia areata trial? Yeah. Well, we've published that as well. So in our second publication, which captured the results of our phase 1A and phase 1B studies, we presented those kind of results. So we do see that in some people, not in all people. To build up with time. So REZPEG, for example, causes TREGs that are instantly elevated from the very first dose. NK cells are sporadic. We don't see them in all people. And when you do see them, they seem to take longer to present themselves. And then one thing that's very curious is we changed the skewing of the NK profile, right? So as you know, there are CD56 bright and CD56 dim NK cells, and those differ in the expression of FcγR3a (CD16). And in normal situations, or well, I guess in one kind of immunological state, you typically have primarily CD56 dim, CD16 high. REZPEG doesn't induce those cells. It induces the CD56 bright, CD16 negative NK cells, which many people have postulated actually have regulatory functions. So it does induce NK cells sporadically, and when it does, it skews them into that other, possibly more regulatory phenotype. And we've published those results. Great. Thanks for revisiting that. Thank you. Our next question will come from Andy Hsieh from William Blair. Your line is now open. Great. Thanks for taking our questions. Appreciate the update. Just two quick ones. One on TNF-R2 validation that you mentioned, Zalevsky. Just to clarify, are you referring to kind of human genetics validation on a population basis to de-risk the mechanism? And secondarily, for 255, so the phase 2 JAVELIN Bladder Medley study, I think the last time you mentioned that there could be a second-half update. So curious about first the timing for that and also the disclosure. So would that be in conjunction with a partner? Would that be kind of Nektar disclosure? Just trying to get a sense of the logistics there. Thank you. Yeah, let me answer the second part of it first, and then I'll let JZ go on. Look, we do expect data from the Medley bladder cancer study in the second half of this year. Don't have an exact date yet. And we will certainly disclose it once the data has been cleaned up and Merck KGaA has looked at the data, cleaned it up, discussed it with us, and we go through a normal process. But I would expect that to all happen in the second half of this year. Great. Thanks, Howard. Any comments? Sure. Andy, thanks for asking a human genetics question. That's super cool. So TNF-R2 validation comes from a number of different sources. And before actually touching on human, let me touch on a few of the critical preclinical findings that have been made. So TNF-R2 has both been overexpressed, and it's been knocked out. And you see the kind of corollary phenotypes. When it's gone, animals have a hard time maintaining TREG populations. They also have a hard time mounting any kind of burst of TREGs or TREG control in the setting of a model like EAE, for example. If you run EAE in a TNF-R2 knockout, the disease is extremely exacerbated, right? And it's much, much worse than it is. And whether you use MOG or PLP, you get similar kind of results. Likewise, when you drive its expression, you can reduce the ability to even insult using various inflammatory agonists. Also, studies that have made transmembrane TNF mice, some of the studies that Jonathan Sedgwick did in the early 2000s. Since that's the primary ligand, you really get TNFR2 signaling as the primary signal model. And again, you had very similar kinds of effects where those animals were driving R2, and they remained highly immunoregulatory. It was very hard to create an inflammatory model in that background. And then people, we see a kind of cluster of SNPs and other kind of polymorphisms that go together. So first, the most canonical sort of TREG-like dysfunction is IPEX, right? And IPEX in humans is when you have a FOXP3 loss of functions, very severe autoimmune, almost SCID type of disease. Actually, TNF-R2 SNPs and things that modify TNF-R2 expression or signaling actually can resemble IPEX, just not be as severe because obviously, knocking out Fox P3 is much more severe than losing TNF-R2. So I hope that answers your question. There are many, many streams of validation of TNF-R2. And probably, I guess that one more is actually just sort of coming from the field of using TNF inhibition, right? So we know that if you treat with a pan-TNF inhibitor like Humira or Remicade or Golimumab, pick your favorite one, right? They knock out transmembrane and soluble, and you see that that's contraindicated in a number of indications. And it's removal of that transmembrane that takes away the TNF-R2 signal that kind of short-circuits what you're trying to achieve therapeutically. So all of those roads kind of lead to Rome, and they've really led the field to come to understand that the two receptors, R2 and R1, they share very differentiating functions, and that R2 is like the natural antagonist to R1, and it seems to turn off that inflammatory pathway that TNF-R1 drives. It's highly tissue protective. So to create an agonist to capture that kind of biology could be really, really therapeutically ideal, and that's what we're trying to do. That's super helpful. Thank you. Thank you. As a reminder, to ask a question, please press star one one. Our next question will come from Arthur He from HC Wainwright. Arthur He, your line is open. Hey, good afternoon. Howard and team. This is Arthur from H.C. Wainwright. Thanks for taking my question. Just maybe first question for Mary. So are you guys open to evaluating REZPEG in the patients with biologic experience, either with a single agent or in combination with a biologic through kind of collaboration or IST? Yeah. Hi, Arthur. That's a good question. So we talk a lot about this internally. Generally speaking, the FDA requires you to ensure that patients who are biologically experienced have a washout period of five and a half half-lives. And so patients who have previously been exposed to another biologic agent have to be off treatment for about 12 weeks. So some clinical trials have permitted these patients to be enrolled, but because of the very long washout period on their prior agent, it ends up being pretty difficult to actually enroll these patients, even though scores of patients have been exposed to, say, Dupixent. So it is something that we're considering for the phase 3 program, how or potentially if we would include those patients into our study. Then we always, J.Z. and I and Jennifer have spoken many times about whether or not we would ever do a combination trial, say, REZPEG with an IL-13 inhibitor. So we've also spoken about that a lot internally, and it's certainly on our list of clinical trials to consider. For us, though, the primary goal is excellent execution of the phase 2b, seeing the data, and should that be positive, to move very quickly to a program that would allow REZPEG to get to patients as quickly as possible. Thanks, Mary. My second question is for the 165. Just curious, what are the gating enabling studies right now for these programs moving to the clinic next year? J.Z., you want to cover that? Sure. Hey, Arthur. Thanks for the question. So we've advanced the program, as I mentioned earlier, to identifying candidates and then to characterizing it in vitro and in vivo. We've also run large animal studies, like a non-GLP toxicology study. We've also moved into, we made a manufacturing cell line, and we've also moved into the beginnings of manufacture. So the next big milestones for our IND-enabling package, which is no different than any other IND-enabling package, right, is the GLP toxicology, which for us will come at the end of the year. It'll start then. And then also advancing into GMP manufacture of the Phase 1 supply. But as I said, we've already done a lot of work and a lot of the major work, like non-GLP toxicology studies and primates, for example, that give us the confidence to move through these IND-enabling studies. Awesome. Thanks, Jay-Z. I'll talk to you guys soon. Great. Thanks, Arthur. Thank you. I am showing no further questions from our phone lines. I'd now like to pass the conference back to Howard Robin for any closing remarks. Okay. Well, thank you, everyone, for joining us today. We remain focused on executing on the development of REZPEG and, of course, our other immunology programs like NKTR-0165. I want to thank all of our employees for their extremely diligent and hard work. The coming year should be an exciting one, and we look forward to providing you with updates on our progress. Thanks for joining us today. Appreciate it. This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a wonderful day.