Good day, and thank you for standing by. Welcome to the Upstream Bio Phase II Top-Line Results for the Phase II VALIANT Trial and Severe Asthma 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'll now turn the conference over to your first speaker today, Meggan Buckwell, Director of Corporate Communications and Investor Relations. Please go ahead. Good morning, and thank you for joining us today. Before we begin our formal comments, let me remind you that during today's webcast we will be making forward-looking statements that represent the company's intentions, expectations, or beliefs concerning future events. These statements represent our views as of this date and should not be relied upon as representing our views as of any subsequent date in the future. With me on the call today are Upstream Bio CEO Dr. Rand Sutherland and Upstream Bio Chief Medical Officer and Head of R&D Dr. Aaron Deykin. Looking at our agenda, Rand will begin the call with an overview of the results, an introduction to Upstream Bio, and our plans for our lead asset, verekitug. Aaron will then review the phase II VALIANT clinical study top-line results in detail, after which Rand will conclude the call and management will take questions. I would now like to turn the call over to Rand Sutherland. Thank you, Meggan, and thank you all for joining us today. Today we are thrilled to share the top-line data from VALIANT, our phase II placebo-controlled randomized trial of verekitug in adults with severe asthma. As Aaron will share in detail in a few minutes, data from this trial, in which patients were observed for up to 60 weeks, demonstrated that verekitug treatment resulted in a statistically significant and clinically meaningful reduction in the annualized rate of asthma exacerbations, or AAER, with both 100 milligrams administered every 12 weeks, or four times per year, and 400 milligrams administered every 24 weeks, or twice per year. In addition, although this trial was not powered to detect statistically significant differences in secondary endpoints, both treatment regimens also delivered clinically meaningful improvements in lung function, measured by the forced expiratory volume in one second, or FEV1, and exhaled nitric oxide, or FeNO, an important disease-related biomarker. A third low-dose treatment group, 100 milligrams q24 weeks, demonstrated a statistically significant effect on AAER as well but did not provide consistent improvements in other endpoints. With 100 milligrams administered every 12 weeks, verekitug resulted in a statistically significant 56% reduction in the AAER, which was accompanied by a 122 milliliter improvement in the FEV1 and by a 20.4 part per billion reduction in exhaled nitric oxide, representing a mean 43.5% reduction from baseline. With 400 milligrams administered every 24 weeks, or twice yearly, verekitug delivered a statistically significant 39% reduction in the AAER, a 139 milliliter improvement in the FEV1, and a 26.3 ppb reduction in FeNO, representing a 44.9% reduction versus baseline. As part of our pre-specified statistical plan, we also analyzed key secondary outcomes after 24 weeks of treatment, and as Aaron will show, we observed statistically significant placebo-adjusted improvements in lung function and exhaled nitric oxide with both dose regimens. Importantly, verekitug was generally well-tolerated across all dose regimens tested in this trial, demonstrating a favorable safety profile consistent with previous studies. We are thrilled that data from this trial continue to validate the very consistent preclinical and clinical data supporting differentiated potency and clinical efficacy of verekitug, and the data from this trial further support our hypothesis that verekitug may deliver a unique and meaningfully differentiated profile versus other therapies. Now, both in severe asthma and chronic rhinosinusitis with nasal polyps, we have compelling evidence from placebo-controlled studies using clinically important and potentially registration-enabling endpoints that verekitug can deliver efficacy that meets or exceeds that of currently available biologic therapies, with significantly less frequent dosing. Because of the potential for verekitug to help address significant remaining unmet clinical need and to address substantial associated commercial opportunities, Upstream Bio is positioned to quickly advance this molecule into phase III studies in both indications, pending interactions with regulatory authorities. Before I turn the call over to Aaron to review the trial results in further depth, I'd like to update you as to where we stand today as a company. Upstream Bio is a clinical-stage immunology company, and our initial focus is on severe respiratory diseases. We are developing verekitug, the only known antagonist of the TSLP receptor. After analyzing these data, our corporate strategy remains unchanged, namely to focus on helping patients with severe respiratory diseases and to maximize the value of verekitug across multiple indications with unmet need. VALIANT, our phase II trial in severe asthma is reporting data today. VIBRANT, our phase II trial in CRSwNP delivered positive top-line results in September. VENTURE, our phase II trial in COPD, is actively enrolling participants. Today, we are happy to report that enrollment in the VENTURE trial is over 60% complete, far exceeding our predicted timelines and driven in part, we believe, on the basis of investigator feedback, by enthusiasm for verekitug's potentially differentiated clinical profile. Upstream is developing verekitug in common airways diseases with substantial remaining unmet need, and there is substantial potential commercial opportunity in this space. Our focus today is on severe asthma, where it is estimated that approximately 1.3 million patients in the United States are eligible for treatment with biologic therapies. Despite well-defined eligible patient populations and clinical benefits, no more than 25% of currently available patients currently eligible patients are estimated to be receiving biologic therapy today, indicating that there is still substantial commercial opportunity for novel biologic drugs, which can further drive prescribing in eligible patient populations. It is estimated that by 2033, global peak sales for biologics in severe asthma will exceed $12.5 billion, and targeting the role of TSLP in severe asthma has been validated clinically and commercially. Our ambition is to deliver a clinical profile that allows verekitug to compete successfully for share in the biologic space, not only versus TSLP targeting agents but also versus drugs targeting IL-4, IL-13, IL-5, and IgE. With that introduction, I would like to turn the call over to Dr. Aaron Deykin, Upstream's Chief Medical Officer and Head of R&D, to take us through the details of the top-line VALIANT phase II data. Thank you, Rand. First, let's review the VALIANT study design. VALIANT was a phase II randomized double-blind placebo-controlled parallel group clinical trial designed to assess the efficacy and safety of verekitug in adult patients with severe asthma. Eligible patients who were enrolled from the US and 14 other countries in Western Europe, Central Europe, Africa, South America, and Asia had a documented history of asthma, an FEV1 between 30%-80% of predicted, with evidence of reversible airflow obstruction, ongoing symptoms despite standard-of-care therapy, and a documented history of asthma exacerbations, as indicated on the slide, within the past 12 months. 478 participants were randomized in a 1:1 to 1:1 allocation to verekitug 100 milligrams every 12 weeks, high dose; 400 milligrams every 24 weeks, medium dose; 100 milligrams every 24 weeks, low dose; or matching placebo. A double dummy design was used to maintain blinding for both dose level and dose frequency. This trial included a variable treatment period, with all subjects having at least 24 weeks of treatment. Subjects enrolled prior to the last subject randomized had additional treatment up to a maximum of 60 weeks. Based on this design, the study had 90% power to detect a 50% reduction in the primary endpoint of annualized asthma exacerbation rate in each active arm as compared to placebo. Importantly, the study, based on the overall sample size and the relatively smaller 60-week dataset, was not powered for the secondary endpoints of change from baseline to week 60 in pre-bronchodilator FEV1, FeNO, and the six-element asthma control questionnaire, or ACQ. In this regard, we pre-specified analyses of the secondary endpoints at week 24, a time point which was assessed to have the largest amount of data for these measures. Throughout the trial, safety was carefully monitored and characterized in collaboration with a data monitoring committee. Now, reviewing the disposition of the ITT population, 478 patients were randomized, with 121 randomized to receive high-dose verekitug, 118 to receive medium-dose verekitug, and 120 to low-dose verekitug, with 119 to placebo. The proportion of patients randomized to each dose group that completed the protocol-defined treatment period was similar across the dose groups and consistent with our design assumptions regarding sample size and total duration of follow-up. As we look at the baseline characteristics for the participants in the trial, we see that they were consistent with the design of the study, reflect those anticipated for an uncontrolled severe asthma population, and were generally balanced across dose groups. Considering safety, we were pleased to see that verekitug treatment was generally well-tolerated, with a profile consistent with our previous studies. Overall, the incidence of TEAEs and TESAEs were similar across treatment groups, although there was a numerically higher incidence of SAEs in the placebo group. No deaths reported in the study, and the most commonly reported AEs are listed here and appear to be equally common across active and placebo, although events described as bronchitis occurred with numerically greater frequency in high and medium-dose verekitug as compared to placebo. Consistent with the findings we reported from our phase I studies, anti-drug antibodies were observed in between 50%-60% of subjects. The prevalence and titers of these ADAs were stable over time and did not vary by dose group. There was no impact of ADAs on the incidence or type of AEs. One subject in the study randomized to placebo experienced an AE of anaphylaxis during the study. Now, turning to efficacy, we are pleased to report that in the VALIANT trial, verekitug at all doses studied, including both the Q12W and q24w regimens, demonstrated clinically and statistically significant effects on the primary endpoint of annualized asthma exacerbation rate over 60 weeks. Specifically, we observed a 56%, 39%, and 49% reduction as compared to placebo, with verekitug at 100 milligrams every 12 weeks, 400 milligrams every 24 weeks, and 100 milligrams q24w, respectively. While not powered for these, we did observe generally consistent trends for benefit across the secondary endpoints at 60 weeks as compared to baseline, including point estimates for placebo-corrected FEV1 improvements of 122 mL and 139 mL with 100 mg Q12W and 400 mg q24w dosing, respectively, and substantial and statistically significant placebo-corrected reductions in exhaled NO. Generally lower treatment effects were observed with treatment with 100 mg every 24 weeks. Now, considering the efficacy endpoints over time, we clearly see here that while the number of subjects with 60-week data is substantially lower as compared to those at week 24, as shown in the tables below the figures, and anticipated due to the variable treatment period design, the effects on lung function and biomarkers were evident rapidly and appear to be consistent over the full 60-week treatment period, including a mean placebo-corrected 43.5% and 44.9% reduction in exhaled NO at week 60 as compared to baseline, with high and medium-dose verekitug, respectively, that is evident by week 2. Now, as mentioned previously, and with anticipation of the larger quantity of data at week 24, we pre-specified examination of the secondary endpoints at that time point. This analysis indicated substantial, statistically significant, and generally dose-related treatment effects on FEV1, FeNO, and ACQ with verekitug dosed at 100 milligrams every 12 weeks and 400 milligrams dosed q24 weeks. These results, combined with the observation that the treatment effects of verekitug appear early and are stable over time, enhance confidence that a subsequent registrational trial with a larger number of subjects followed for more than 24 weeks will confirm these phase II findings. When examining the AAER data for high-dose verekitug in clinically relevant subgroups of patients, we observed that the treatment effects are generally consistent, favoring verekitug over placebo, and this includes subjects recruited from Central Europe as compared to the US and Western Europe. As expected, treatment effects were somewhat numerically larger in subjects with higher levels of eosinophils or FeNO at baseline, although this was not consistently observed across endpoints. Indeed, on FEV1 improvements were very similar in high and low T2 biomarker groups. As the study was not designed to compare efficacy in any subgroups and the sample sizes in these subgroups are quite small, a larger phase III study will more clearly define the relative treatment effects in these patient subsets. In summary, we're pleased to report that verekitug delivered statistically significant and clinically meaningful reductions in asthma exacerbations with 100 milligrams q12 weeks and 400 milligrams q24 week dosing. These findings were accompanied by meaningful improvements in lung function, as reflected by FEV1 and exhaled nitric oxide, with both dose regimens that were evident as early as two-four weeks and were maintained over 60 weeks. As observed in the prior clinical trial experience, verekitug was generally well-tolerated in this study in patients with severe uncontrolled asthma. These trial results further extend the consistent body of preclinical and clinical data from our development program, which together suggest a potential for verekitug to provide meaningful clinical benefit in CRS with NP and asthma at a significantly reduced dosing interval compared with other biologics. The data to date reinforce our belief that the differentiated profile we were observing with verekitug is driven by verekitug's unique mechanism of action. We're very pleased with these data and look forward to maximizing the impact of verekitug for the treatment of severe respiratory diseases. With that, I'd like to turn back now to Rand. Well, thank you very much, Aaron. As I hope you can all hear, we are very excited about the positive trial results we are reporting today. With these data in hand, we have a clear path forward to phase III development in severe asthma and CRSwNP. As always, our decision-making will be rigorous and data-driven and will be paired with rapid execution. Our first priority is a comprehensive integrated analysis of the hundreds of patients' worth of data from the phase II VALIANT and VIBRANT studies to inform dose optimization and selection across severe asthma and CRSwNP. Based on those insights, we plan to engage with regulatory agencies to align on the phase III development strategy and move as quickly as possible to initiate phase III trials in both indications in parallel. At the same time, we will continue to both progress enrollment in our phase II VENTURE trial in COPD, now over 60% enrolled, and make substantial investments in CMC and device development to support a potential launch. As we conclude, on behalf of the entire team here at Upstream Bio, I would like to thank the patients who participated in VALIANT, along with our clinical trial investigators and site staff who collaborated with us to execute this important trial. Your support and participation have helped us meaningfully advance the development of a potentially new treatment option for severe asthma, and we hope for other respiratory diseases as well. And lastly, to our outstanding team here at Upstream Bio, I appreciate all of the dedication and outstanding work that each of you put in every day. Thank you. And with that, we're happy to take questions. Operator? Thank you. At this time, we'll conduct the question-and-answer session. As a reminder to ask a question, you will need to 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 limit yourself to one question. Please stand by while we compile the Q&A roster. Our first question concerns Danielle Brill of Truist Securities. Your line is now open. Hi, guys. Good morning. Congrats on the positive outcome here, and thanks so much for the questions. I guess I have a couple. First, I just wanted to ask, as we think about these data translating in a large phase III study, as we look at the Tezspire and, I believe, Dupixent phase IIs, there was some reduction in the magnitude of AER benefit from phase II to phase III. However, the other biologics did not show this deterioration of effect. Are there any study design factors that could account for these shifts, and how confident are you that the magnitude of benefit observed in VALIANT will be maintained in phase III? And then I have a quick follow-up. Yeah. Hi. Thanks for the question. Certainly, we're aware of the fact that some biologics have shown reductions in treatment effect going from phase II to phase III. I think generally, there can be a couple of reasons behind that, including just regression to the mean because you don't advance a program that doesn't have good data, so you're cutting off the tail end of the distribution of the treatment effect from phase II to phase III. I do think that phase II trials, generally because they are lower in sample size, and this includes our trial as well, can have some variability in terms of the results. For example, in the tezepelumab study, there were many aspects of that study, that is, the PATHWAY study, that didn't bear out in phase III, including dose response or lack thereof observed in PATHWAY, and then also interesting features of the biomarker subgroup data with respect to efficacy. Overall, I think that we have, in our dataset, a lot of internal consistency across the doses studied, with multiple doses showing strong clinical effects. Also, we have a very strong throughline from our preclinical to our early clinical to now our clinical data in two different indications. So we do have a lot of confidence that verekitug is highly active in the diseases we're studied and that our future phase III trials will confirm that finding. Great. Very helpful. And then I just wanted to ask on next steps and plans for phase III. In the past, I know you communicated that you were intending to advance just a single dose. However, you do have clear efficacy at the 24-week dosing interval here. Have your thoughts changed, or what are the next steps in evaluating which dose to advance with? Thank you. Yeah. So thanks for the question again. So I think in many conversations we've had with many of you and also in other settings, we've been pretty clear that we did anticipate that there would be clinical activity at the top two doses. And I think we've seen that here. We were pleasantly not necessarily surprised, but we were pleased to see also that even the lowest dose had statistically significant activity, at least on asthma exacerbations. So to an extent, we have an embarrassment of riches. I think that the decision around which dose to take forward or dosage to take forward into phase III is probably one of the most important ones that we will have to make with this development program. And we're not going to be making it lightly or rapidly. We're really going to be examining all the pharmacology data, not only from this study but from our CRS with NP study, and making a very data-driven decision. So at this point, I don't think we're in a position to make any strong commitments about the design of the phase III study, except to say that we're in a very good position having had these results from the VALIANT study and are going to be doing so in a very thoughtful way. Understood. Thanks so much for the questions, and congrats again on the data. Thank you. Thank you. Thank you. One moment for our next question. Our next question concerns Tessa Romero of JP Morgan. Your line is now open. Good morning, Rand and team. Thank you so much for taking our questions this morning. So it looks like to us that the FeNO results that you saw were pretty comparable across the 100 mg q12 week and 400 mg q24 week dosing groups in terms of the mean reductions that you saw from baseline in each of these groups. But it seems like you also saw a difference on AAER reduction between the groups. So we're really just trying to think through a little bit here what the factors could have been that contributed to this separation. Any current thoughts that you might be willing to share on this point first, and then I have a quick follow-up. Yeah. Hi, Tessa. It's Aaron here. So number one, I think it's important to recognize, and we talked about this just at the beginning, that the trial was designed to compare with respect to AAER, designed to compare each dose to placebo. It was not designed to have enough resolution to discriminate clearly between the doses on AAER. And in that regard, this is why it's going to be very important to do a very detailed analysis comparing modeling pharmacology to clinical outcomes. I think that when we examine the data, even just as we've presented, we do see well, there are differences. While there are very substantial mean reductions for both 100 q12 and 400 q24, the pattern of those reductions over time may be slightly different and could actually give some insights into how much activity is being manifest by those two different dose regimens. I do not find the AAER versus FeNO results to be perplexing, but rather much more of a reflection of what the limitations of a trial of this size are with multiple dose groups. Yeah. Okay. Great. That's helpful. Thank you. And then just as a quick follow-up, when you speak to doctors, how do they stack up every four weeks as with Tezspire versus every 12 weeks versus every 24 weeks for a new asset in the severe asthma space? Thanks. Well, hi, Tess. Thank you for the question. I think it's been very clear to us since the inception of the program that if we were able to show that verekitug's potency translated to efficacy that, again, met or exceeded that of available biologics and did so at q12 or q24 week dosing intervals, that that would be a big win. That comes from a lot of one-on-one conversations. It comes from our own clinical experience. And it also comes from formal market research where we've tested this exact profile against biologics that are dosed every two or four weeks. So we are, again, thrilled with the data that we show today. I mean, the efficacy in terms of asthma exacerbation that we've demonstrated is at the top of the line. And to do this at every 12-week dosing, it could have happened through no other mechanism other than potency. Back to Aaron's point about the throughline, consistently since the preclinical days, the early clinical days, and now in mid-stage clinical trials in two divergent but type 2 inflammation-driven diseases, we've seen that this pharmacology profile translates to something that is unique. We're very excited. Again, we need to do some work to make some decisions about dose and design for phase III, but we believe that there's value here, and we're going to move as quickly as possible to develop it. Thank you. Thank you. Thanks, Tess. Thank you. One moment for our next question. Our next question concerns Yasmeen Rahimi of Piper Sandler. Your line is now open. Good morning, team. Thank you so much, and congrats to the data. Team, obviously, very rich dataset that very much de-risked the phase III readout and gets us very excited. You noted you're starting on the phase III planning as soon as possible. Maybe help us understand, with this data on hand, what analyses you hope to complete over the next few weeks and few months as you're going to be going and engaging with the agency for phase III design. So I think yes. Maybe also, this was a phenomenal execution, so help us think about the thought process on what are some things dosing. Maybe help us understand what work will you do to understand which dosing regimen to move forward, and then what do you hope to do change in the phase III protocol? Or is it the idea just of larger sample size but keep it very consistent? So any nuggets of details that you're going to help us provide now on what's going to be happening over the next few months, that's going to be very helpful for us. And then our second question is, I think investors and us tend to forget that the biological asthma space is so under-penetrated with only 20%, and the growth of new agents is going to continue growing that. Rand, would love to get your experience on the growth of the market, what it means. This is not a market of one takes all. Appreciate color on both of these topics from you guys. Hi, that's Aaron. I'll take the first part, and then Rand will discuss the second. So thanks for your comments on the data. We're very excited about them. I will note that we've been in possession of these analyses now for such a very short period of time. So I want to caveat what we're saying and what our plans are by the fact that this is all still very, very fresh. But on the highest level, the most important aspect here with respect to dose is to relate the exposures that we see in the trial, but not only this trial, but all the other studies, so the drug exposures, to efficacy to try and resolve as quickly and as definitively as possible what concentrations of the drug are necessary to drive the greatest efficacy that can be extracted from verekitug. We're in a very fortunate position that verekitug, across multiple studies, has demonstrated a very clean safety profile. We know from our preclinical toxicology that we have ample margins so that we have the opportunity now to really select a dose without concerns about encroaching on any margins or a safety concern that maximizes efficacy. That really is going to be done by examining exposure relationship to efficacy, both clinical efficacy and biomarker efficacy. Those analyses take a lot of time. We need to aggregate a lot of data and really also engage specialist experts on a consultative basis to help us complete those. We're going to be doing that. It's already underway, but it will take a bit of time to complete. Subsequently, we need to interact with regulators to share our plans, and then we'll be able to move forward into execution, which we're going to be doing as rapidly as possible. And yes, thanks for the question on the market opportunity. We, I think, look at it in this way. First, we're developing this drug in three indications, three indications which are prevalent, which are growing, and which are benefiting, I think, in terms of evolution from the role that novel biologics are playing in terms of modifying the long-term outcome of the disease. So it's a very dynamic market, as you mentioned, and it's one that, if you look back even into the last decade and follow forward over time, it is characterized by a few dynamics. The first is that we've got multiple biologics targeting multiple different pathways in different patient subsets with different types of outcomes depending on which patients were studied. And so you have this really diverse set of tools that clinicians can bring to bear to make a decision about what's going to work best for a patient. So that has led to a circumstance, in our opinion, that drives a market in which novel entrants can actually come in and take substantial share. And they take that share not by eroding the share of others but by actually driving penetration, to your point. And so what we think is sort of a sine qua non for success in the market is something that's different and hopefully better, and better and different in what way. And we think it can break out in a few different ways. It could be total efficacy. It could be eligible patient populations. Of course, now, as we're seeing with our data and a lot of the competitive environment, patient convenience and dosing interval as well. So we see a very clear white space where this profile that verekitug has delivered occupies. If we are able to prove that out in phase III and negotiate a label that supports that, we would anticipate having one of these novel and differentiated entrants and, for that reason, be able to take advantage of the fact that, again, the epidemiology is significant, the penetration is low, and to be able to drive a significant share for verekitug. That's all hypothetical and forward-looking, but that's the ambition. Again, we're moving as quickly as we can to realize it. Thank you. One moment for our next question. Our next question, concerning Yaron Werber of TD Cowen, is now open. Great. Thanks so much and congrats on really nice data. A couple of questions for you. The first one is we got a lot of questions on competition, and I think your data shows the variability on AAER. When you look at even the 100 q24, it actually looked really good on exacerbations. Obviously, the rest of the data for that dose didn't look as good. But can you talk about, just so we all sort of have the background info, what really drives exacerbations in studies and why you see so much variability? And then secondly, I mean, you're enrolling really quickly in COPD, so you're probably just kind of straight-shotted. And typically, enrollment's even accelerating, so you should be fully enrolled by mid-year. And I think it's a one-year study. But can you give us a little bit of a sense kind of how you're thinking about COPD? Would you potentially change and add a dose, maybe remove the 24 weeks, and maybe add another higher dose to the q12 weeks in that study as well? Thanks so much. Right. Hi, Yaron. It's Aaron. Thanks for the question. I'll address your first one, and then maybe Rand will take your second about COPD. So asthma exacerbations are stochastic events. They certainly are related to the patient's underlying risk for exacerbations, which is driven by their inflammatory tone. But very frequently, exacerbations are then finally triggered by exposures to elements in the environment, which can occur somewhat randomly, although in some cases, there's a seasonal variation. All of that nets out to there's a lot of variability in terms of what can drive an individual person to have an asthma exacerbation, and thus, there's a lot of variability in observed asthma exacerbation rates in trials. Factors that can be controlled or that can, on an average basis, lead to higher or lower exacerbation rates include, number one, how frequently the patients have had exacerbations in the recent past, their level of inflammatory biomarkers at baseline, and how effectively they are managed with background medications. Those aspects can be controlled by inclusion criteria, but the other aspects, in terms of just random events that patients are exposed to, can't. That is why, ultimately, there is a substantial amount of variability in the asthma exacerbation rate readout. That's particularly true in trials of smaller sizes. While I think the fact that we were able to show a statistically significant reduction in asthma exacerbations across all three doses actually speaks to how effective verekitug is. But beyond that, and I think I mentioned that, I think we have to be careful about drawing conclusions about different doses and overall efficacy of different doses, particularly the top two doses, just on the basis of numerical differences in the asthma exacerbation rate. I do believe, though, that these very strong data are substantially de-risking for what we will expect to see from asthma exacerbations moving forward into phase III. So we're proceeding forward with a lot of enthusiasm on that point. And Yaron, maybe to just sort of reference the first part of your question about competition, yes, there's a lot going on in this space. I think Aaron's beautiful summary just now really reflects the things that drug developers in this disease have to grapple with. We're very happy that we have taken a methodical approach to developing this drug, and we're very happy that we now have hundreds and hundreds and hundreds of patients' worth of data as we go into dose selection and phase III trial design. We think that's very important. It helps us understand and account for a lot of this variability, and we think it's going to give us an advantage in terms of de-risking the asset and how much risk we're going to be carrying forward in phase III. I think on COPD, it's a little bit too early to say. Yes, we are ahead of schedule, and yes, you can do some arithmetic and predict where we are. I do think we need to, again, work through these data, really understand what our plans are for phase III in the first two indications, and ask, "Does that have any implications for our COPD program, and do we need to do anything now?" Our sense now is that we're going to, again, continue full steam ahead, but this is drug development, and we reserve the right, if needed, to change. But right now, no change. And once we work through all this, we'll be certainly giving the market some clearer guidance on timelines. Question. Our next question, concerning Matt Phipps of William Blair. Your line is now open. Good morning, guys. Thanks for taking my questions, and congrats on the positive data from verekitug here. I realize this might be too noisy to read into, but was there any variability in the exacerbation rate over time or clustering of exacerbations at that 400 mg dose? Did you see more in the week 16 to week 24 timeframe for that dose? And then can you talk about the form factor that you all plan to use for a phase III trial? Just wondering if you'll have that autoinjector ready for the phase III. And maybe what would you view as risks of starting a phase III with a vial and syringe, like maybe some of your competitors, and then having to transition post-phase III to an autoinjector? Thank you. Right. Okay. So a bunch in there. No, we haven't done detailed analyses on the temporal distribution of the asthma exacerbations, but just on the basis of what we're seeing at the highest level, I would be very surprised if there were substantial clustering of exacerbations around end-of-dosing, for example, which I think might be the implication of your question. So more to come there, but I would be surprised if that is something that we end up seeing. I think that in terms of moving ahead into phase III, firstly, we won't be doing that with vials. We'd be doing it with a prefilled syringe. And then we would aim to also, in parallel, develop the autoinjector in parallel with phase III. The goal is to be able to launch with both an autoinjector and a prefilled syringe. There are ways of doing that that we're planning for at the current time. Thank you. One moment for our next question. Our next question comes from the line of Cory Kasimov of Evercore ISI. Your line is now open. Hi. This is Josh on for Cory. Thanks for taking our question. As part of your dose selection for phase III, would you be considering, if you were to find that the 400 mg arm wasn't performing as you would expect, would you be open to considering, instead of a q24 week, maybe a q20 week or some sort of mediate to close the gap or the perceived gap between some of these q6 months YTEs that are coming out? Thank you. Yeah. I don't think that we're going to be definitive about taking anything on or off the table there, but I will just comment that both based on just my own clinical experience and then talking a lot to physicians both through conversations and through formal market research, there are general parameters of dosing frequency that make sense in the clinic. And those are generally monthly, then every three months, and then every six months. I think that something that falls off that—and we have talked about this explicitly with practicing clinicians—doesn't get an incredibly warm reception and would feel odd to folks. So while I'm not saying that anything is absolutely off the table, I don't think that an off-cycle regimen is likely to be something we would pursue. Thank you. One moment for our next question. Our next question, line of Katherine Dellorusso of LifeSci Capital. Your line is now open. Hi, team. Congrats on the positive readout, and thanks so much for taking the questions. Just a couple from us. First, I was wondering if you could comment or just elaborate a little bit on the dose and relative need for target coverage across different indications as asthma, nasal polyps, and COPD as you're considering go forward dosing. And then as a second, just wanted to ask if you had any additional color on the ADA rates, if you know anything about whether or not they're neutralizing, and if you think that had any impact on drug levels or efficacy going forward. Yeah. So in terms of coverage, I think the data from our CRS with NP trial and also our asthma study are very consistent in terms of the efficacy that was delivered at the 100 milligrams every 12 weeks. So really efficacy consistent, for example, with tezepelumab on both metrics, asthma and CRS with NP, at a regimen that's delivered at much lower dosing frequency. So we're pretty confident that a dose selection strategy that pursues a unified dose for asthma and CRS with NP is the appropriate way to go forward. COPD is, I think, a little bit more of a question, and that's why we're doing dose-ranging trial in COPD, specifically because that indication ultimately may require a different dose, either a different dose level or a different dose regimen. And so that's why we're going to have to be waiting for COPD data to ultimately make a decision about that indication. But we're going to be making a unified dose decision for the first two indications based on the aggregated data. In terms of ADAs, as we mentioned in the slides, we saw an ADA incidence that was very consistent with our prior experience. We do know that ADAs can impact exposure, but whatever impact of exposure was observed here, the efficacy is net of that. It was an important observation that the incidence of ADAs over time and also the titers of ADAs over time in this study and also just parenthetically in prior studies does not change, so that we really don't have a concern that whatever impact ADAs have on exposure is going to change over time and possibly lead to different efficacy as drug treatment continues. So we've seen strong results net of ADAs, and we're quite happy about that. Great. Congratulations again. Thank you. Thank you. Thank you. One moment for our next question. Our next question from Joe Catanzaro of Mizuho. Your line is now open. Hey. Thanks for the update. Thanks for taking my questions. Maybe a couple on dosing here. I think this was tried to ask earlier, but I'll ask it again, whether you believe you've maximized the efficacy with the 100 mg on the q12W schedule, and if not, whether there's any opportunity to explore that. And then second, with the intention that VALIANT will serve as part of the registrational data package, does that then imply that a phase III dose is going to have to leverage a dose and schedule that was used in VALIANT, or is there any opportunity outside of that? Thanks. Yeah. So with respect to the question about whether or not there's an opportunity for additional efficacy at a dose that's higher, for example, than 100 milligrams every 12 weeks, I think that that is exactly one of the questions that we're going to be looking at with regard to our PKPD modeling. Our modeling in phase I, which was in a healthy volunteer or mild asthma population, indicated that 100 milligrams every 12 weeks was likely to provide the maximal level of efficacy. But I will say that we have to now look at a dataset that's, A, much larger, and, B, includes a substantial number of patients who are exactly those that we would envision being treated with verekitug if it were to be approved. And if that modeling then suggests that there is additional potential for upside efficacy with a dose higher, we absolutely would consider that. In terms of what a change in dosing regimen from phase II to phase III might imply, that's a discussion that we'll have to have with regulators, and I really don't want to get ahead of them or ourselves by commenting on that, except to say that I do think that the phase II study that we've presented here really does form a strong base of support for the efficacy and safety of verekitug, and I would believe that it will be considered as part of a registrational package. The ultimate size of the subsequent phase III study in each indication may be a matter of alignment with regulators, but we haven't gotten to that yet. Okay. Great. Appreciate you taking the questions. Thanks. Thank you. I'm showing no further questions at this time. I'll now turn it back to Rand Sutherland for closing remarks. Well, thank you, everyone, for joining today. We appreciate you taking the time to hear the data from our phase II VALIANT study in severe asthma, and we look forward to keeping you updated on our progress over time. Thank you for your participation in today's conference. This has concluded the program. You may now disconnect.