Upstream Bio is a clinical stage company. We are focused on severe respiratory diseases, and we are prosecuting our program in verekitug. Verekitug is a monoclonal antibody that is targeted to the receptor for TSLP. It is unique in that regard in that everybody else that we know of that is targeting TSLP is targeting the ligand. The reason we make this point is that by virtue of targeting the receptor, we are able to confer some very specific pharmacology upon the molecule that we think gives the potential for differentiation along two axes. The first is efficacy that meets or possibly exceeds that of all currently available biologics in our target diseases. The second is an extended dosing interval driven not by Fc Engineering, but purely by potency alone. For that reason, we are studying verekitug in a number of indications, namely chronic rhinosinusitis with nasal polyps, severe asthma, and chronic obstructive pulmonary disease. We are busy executing and delivering data in that regard as well. We just recently read out the data from our phase II trial in CRSwNP, and that was in September, and we'll dive into those data a little bit. We will be reading out data from VALIANT, our phase II trial in severe asthma in the first quarter of next year. We have also recently initiated patient enrollment in our phase II trial in chronic obstructive pulmonary disease. Now, just to clarify what we mean by phase II, we mean placebo-controlled, randomized, potentially even multi-dose regimen trials, all designed with registrational endpoints, all designed with sufficient power to detect meaningful differences, and all, potentially, if positive, allowing us to pursue a potential path of using these trials as one of two pivotal trials in regulatory submissions. These indications are very important ones. There is substantial disease epidemiology, there is substantial unmet need, and in association with that, there is substantial commercial opportunity. The market for biologics in these indications is estimated to top $35 billion by the mid-2030s. Our hope is that with innovation and differentiation, we will bring something that is, first, of great help to patients, and second, a substantial commercial opportunity for the company. We are well-funded and have capital to further fund our operations through 2027. We've got a great team of folks who've been doing this for a long time, working in the space, the space being both respiratory diseases and clinical development. Of course, there are a lot of folks who are not shown here who are of critical importance and are doing a great job, helping us develop verekitug. Now, what is verekitug? As I mentioned, it's a fully human IgG1. It's targeted to the receptor for TSLP, and it binds the receptor for TSLP in essentially the same sites as TSLP itself. By doing so, it prevents the formation of the heterodimer that's comprised of this TSLP receptor and the IL-7 receptor alpha subunit. When you block the formation of that receptor, you then block downstream signaling. Of course, we know that TSLP has been implicated in type 2 inflammation, but also in type 1 inflammation, and also in fibrotic response as well. We, again, are the only known molecule targeting the receptor. We've learned that the receptor is also expressed at very low levels versus the ligand and also refreshed at a very much lower rate than the ligand. It is really that stoichiometry that drives the potency of the molecule and allows really even very small amounts of the molecule to fully occupy the receptor for up to 24 weeks after the last dose. We've learned all of this through preclinical studies and early phase I studies, both in healthy volunteers and in patients with asthma. As I mentioned, have now actually further shown in large controlled trials that this potency does drive efficacy that meets or exceeds that of available biologics and does it at four times per year dosing. When we started this out, we did not have our CRSwNP data yet. We had our asthma data from our multiple ascending dose trial. I think it is important to mention as we lead into the readout for our severe asthma trial in Q1 of next year that when we look at the potency of the molecule, we look at the effect that this molecule has on its ability to suppress fractional exhaled nitric oxide and blood eosinophils, two highly translatable biomarkers in severe asthma. When we look at our ability to dose this at a far less frequent dosing interval than either tezepelumab or dupilumab or even mepolizumab, we do believe that there's the possibility here for a substantially differentiated profile and with that, a lot of value creation. As I mentioned, we've moved from multiple ascending dose trial data into now placebo-controlled data in a significant type 2 inflammation-driven indication with our data from the VIBRANT trial and CRSwNP. In that trial, we met our primary endpoint of the reduction in the endoscopic nasal polyp score of 1.8 points. We also met all of our secondary endpoints with substantial both clinical and statistical robustness. Importantly, we were able to show an effect that we didn't necessarily anticipate being able to do or see, and that was actually a reduction in the need for surgery and steroids as well. That's essentially a very significant set of data coming out of that trial, very much puts the efficacy of this molecule in class with all the other biologics in the space and does so again at four times per year dosing. We know that the molecule is safe and generally well tolerated, and we do believe on the basis of these data and on the basis of the fact that CRSwNP is very much a type 2-driven disease, that there is a high potential for read-through to severe asthma. I've mentioned already what TSLP does. It's an alarming that's a member of a class of cytokines that sit at epithelial surfaces and almost act as a first sort of line of sense for allergens, infections, environmental irritants, which can actually trigger a lot of downstream inflammatory pathways in the type 2 inflammatory sort of path, the type 1, and again, in fibrosis as well. TSLP plays a clear role in the pathogenesis of the diseases that we are targeting, including severe asthma, chronic rhinosinusitis with nasal polyps, and also COPD. I won't spend a lot of time just given the time limits here in terms of the sort of pathobiology here, but suffice it to say that there's very good biologic plausibility for targeting this pathway in these diseases. We've actually seen de-risking with Amgen's TEZSPIRE, all the way through now to the commercial space in terms of modulating this pathway. I've sort of told you the sort of current end of the story, but suffice it to say that there's a very nice and consistent and clear through line all the way from the preclinical days in terms of this molecule and its potency. We acquired the molecule from Astellas. Astellas did all of the preclinical development and actually the first in human single ascending dose trial. What was seen even in the early days with cytokine elaboration studies and cell proliferation studies is that there was evidence that this was potentially a highly potent molecule with the ability to be dosed far less frequently than every two or every four weeks. As I mentioned, that has continued to demonstrate itself with, you know, both biomarker data and really pharmacology modeling data from the early clinical studies and now into late phase as well. The other thing that we have benefited from is a very nice CMC campaign where we now have a 200 milligram per mL formulation that allows us to give even our highest dose of 400 milligrams in a 2 cc presentation that's compatible with all commercially available auto injector platforms and will be very convenient, if that's the dose we choose. Of course, if we choose a lower dose, it'll be an even lesser injection volume. Our multiple ascending dose trial was, again, conducted in patients with asthma. You see the dose regimens here, A, B, C, and D. Of course, we look at safety as the principal, sort of thing we monitor in these types of trials, but we also had some secondary biomarker data here to help us give a sense of efficacy and also to enable modeling. We were very pleased to see that the safety profile was, first of all, very consistent with tezepelumab in the TSLP space, but also very consistent really with biologics in these indications whereby the safety profile is really quite bland. We are, of course, monitoring this very carefully as we move forward in our clinical programs, but have been, you know, very happy to see a safety profile that has really, we think, shows a high degree of tolerability. Now, in addition to monitoring safety, as I mentioned, we looked at a number of different, sort of PD biomarkers. We are showing a couple of here. First on the left is a study done with peripheral blood mononuclear cells from the patients participating in the trial, in which we essentially did a competitive binding assay and looked at how well verekitug could bind free TSLP receptors and for how long. What you see in the dose regimens, shown here in the various colors, is that even with 25 mgs administered once, you had occupancy, 100% occupancy of free TSLP receptors for 12 weeks. With some of the other dose regimens, you see that actually for up to 24 weeks after the last dose, there was 100% occupancy of free TSLP receptors. This then drove what you see on the right, which is a similarly sort of time course, marked reduction in both blood eosinophils and acetyl nitric oxide. The magnitude of these effects is really quite significant. and, you know, as we'll get to in a minute, when you subject this to PK modeling, the effect that we see and would predict to have on acetyl nitric oxide is actually greater than that observed with tezepelumab. Now, there's a caveat here that all of this is based on data from phase I. We are, you know, continuing to read out the data from our program, and we'll learn a lot more from the CRSwNP trial and the severe asthma trial. Of course, we'll make appropriate dose selection going into phase III on the basis of that pharmacology as it continues to further reveal itself. Noting the modeling that I mentioned earlier, first, of course, I had already mentioned that we would project to have a maximal effect on acetyl nitric oxide that is greater than that of tezepelumab, a 43.4% reduction predicted with verekitug versus about 28% with tezepelumab. tezepelumab. I think even more interestingly is the concentrations of verekitug that are required to either achieve a 50% or a 90% maximal effect. Our EC50 and our EC90 are incredibly low. They're about 300-fold lower than tezepelumab. It's that difference in potency that really drives these drug concentrations that are needed to achieve these important pharmacological thresholds and what really allow us to have extended, and durable, efficacy over the course of 24 weeks after the last dose. When we subject all of this to the kind of thinking and modeling that you do to select doses for later stage studies, here's what we use to select our doses for phase II in severe asthma and CRSwNP and even COPD. What you see here is that, with 100 milligrams dosed every 12 weeks, when you model that out over a 48-week period, the entire modeled population stays well above the EC90 for FeNO over the course of the full 48-week period. Even with 400 milligrams administered every 24 weeks, you see that only for the last couple of days of that dosing interval do the drug concentrations dip below the EC90. Now, the EC90 is a very conservative threshold. You know, if this were an EC80 or an EC50, we would remain above that. We think that there's a very good reason to believe on the basis of these data that efficacy could be observed with Q24 week dosing as well. Again, all driven by potency, not relying on Fc Engineering or any other approaches. When we look at our ability to keep patients above these various thresholds at various dose regimens and compare that with what's been observed in the tezepelumab program, we see that with our dose regimens, in both cases, we keep a greater proportion of patients above the EC90 threshold than does the commercialized dose of tezepelumab. We need to do the trials. We need to get the data. Again, reasons to believe that our efficacy could very much deliver or be, our efficacy could very much look like that of tezepelumab, but again, be delivered at Q12 or Q24 week dosing. We have now shown again in later trials that we can do that. This is the general schema of our phase II trial in chronic rhinosinusitis with nasal polyps. This was a one-to-one, randomized placebo-controlled trial of 100 mgs Q12 of verekitug versus placebo. This was done in a trial population very consistent with the population that others have enrolled in their label enabling studies, both with tezepelumab and dupilumab. We used key regulatory endpoints, the primary endpoint of endoscopic nasal polyp score and key secondary endpoints that include the nasal congestion score, a CT scan index of sinus opacification, a total symptom score. As I mentioned, even the proportion of patients requiring either systemic steroids or surgery. The characteristics are shown here. I will not spend time other than to allow you to look at them. I think, trust me, that these are very similar to what has been enrolled in other trials. Importantly, to note that the drug was well tolerated throughout and continued to demonstrate a profile similar to that observed in phase I. Also importantly, demonstrating a very significant efficacy profile with the treatment differences that you see here. I mentioned the endoscopic nasal polyp score reduction of 1.8 that meets or exceeds that of tezepelumab and dupilumab. You can see the other changes here, a change in the nasal congestion score of almost a one, a full point. The Lund-MacKay CT scan score reduction here, total symptoms, and difficulty with sense of smell also improving. Again, a 76% reduction in this trial in patients who need either surgery or systemic steroids. We were not sure we were going to be able to deliver that. The study was certainly not powered a priori to demonstrate that. The fact that we did demonstrate that is really a sign of efficacy here. I would also point out that our statistical approach actually is different, somewhat different than has been used, at least in the reported, peer-reviewed data from other trials in that we used a very stringent FDA-recommended statistical analysis approach that actually somewhat could even impair our data when compared to others. We feel very good about this profile. It's a very strong one. One that, we think, gives a strong reason to believe, for read-through into severe asthma. One thing that's interesting here is, if you just look to the right at the change in nasal congestion score over time, we focus on this because this is measured more frequently than the endoscopic nasal polyp score. What you see is that there may be, both there and with the endoscopic nasal polyp score itself, evidence that there is room to continue to improve over the course of a 52-week trial and that we need to do the trial to actually see if this is the case. There may actually be a chance here for an even slightly greater degree of efficacy observed at 52 weeks. That is likely to be the duration of our phase III trial. We will see what those data show. Verekitug was really, I think, quite efficacious across a number of subgroups. Here you see them listed on the left: age, sex, region, weight, eosinophil levels, comorbid asthma, nasal polyps, and even the prior use of systemic steroids. With a couple of exceptions where the width of the confidence interval is largely driven by a relatively small sample size, you see that in all cases, the point estimates favor verekitug versus placebo. Very robust, very consistent, and we think very competitive, as I'm showing here, with our molecule delivered four times per year versus every, you know, 13 times per year or 26 times per year, with tezepelumab and dupilumab, we see efficacy that is as good as or better than the other molecules. More to come. We still need to talk to regulators about our approach to phase III. We still need to conduct a full program, but we feel good about our data in this indication, not just within the indication itself, but again, because we know that severe asthma shares similar biologic drivers of pathogenesis, that there is actually significant shared epidemiology with roughly 40%-50% of patients with asthma having CRSwNP and vice versa. Also, evidence from development programs in TSLP, IL-4/13, IgE, and IL-5 shows that in general, the magnitude of effect that's observed in CRSwNP tracks with the magnitude of effect that's observed in severe asthma. You can see dupilumab and tezepelumab here in the sort of top right quadrant of this two by two comparing nasal polyps efficacy versus severe asthma efficacy, with IgE and IL-5s clustered more in the lower left. We still need the data, but we are hopeful of a positive outcome from our phase II trial in severe asthma. That trial is called VALIANT. I'm showing you the details of it here. We have three different dose regimens versus placebo in that trial. We are enrolling patients with severe asthma, and we are using the registrational endpoint of annualized asthma exacerbation rate as our primary endpoint. We have 85% power to detect a 50% or greater reduction in asthma exacerbations. We'll also be looking, albeit without statistical power, at a number of key secondary endpoints, including pre-bronchodilator FEV1, exhaled nitric oxide, the asthma control questionnaire, and of course, carefully monitoring safety. We are doing this in almost 480 patients in a global trial. This is a large, potentially registration-enabling, not as a single trial, but as one of two, contingent, of course, on successful discussions with regulators. We've taken a very similar approach to the design of our trial in COPD, again, using exacerbations as the primary endpoint, again, looking at a number of other key secondary endpoints, again, looking at a couple of different dose regimens here, sorry, three different dose regimens versus COPD, and again, doing this in almost 700 patients globally. Another very large, and we think very important test of verekitug's potential to deliver efficacy with safety in COPD. I won't spend a lot of time on the commercial opportunity. I've already summarized the sort of total number at the beginning, but suffice it to say that even CRSwNP is a substantial opportunity for biologics. We see, I think, greater uptake now of biologics in this indication. We've got dupilumab approved. T ezepelumab was just recently approved. I think we are even starting to see the treatment paradigm change a little bit with greater use of biologics now versus historical trends in terms of, you know, using steroids and surgery. An opportunity there that's continuing to grow. The severe asthma market is quite large and expected to continue to grow because of still the really low degree of biologics penetration into the eligible patient populations and COPD as well as substantial commercial opportunity again. These are big markets where we've learned over time that differentiated assets can come in and perform well. I think all you have to do is look at the launch of TEZSPIRE to see that that remains the case. This is our ambition as well. There are opportunities because of disease biology to take TSLP modulation into other disease areas. Right now, we are focused in the areas where we think the unmet need is greatest, the commercial opportunity is greatest, and the biology is most de-risked. We could look at particularly dermatology and GI as other therapeutic areas over time. With that, I'll close. Again, say thank you. Alex, maybe we have a little time for questions. Yeah, great, Rand. Thank you so much. Definitely a lot to think about. I think, you know, maybe the first question that I would have for you is, you know, obviously you're the only company right now with a TSLP receptor antagonist antibody, but you're not the only company developing, you know, different ways to target TSLP with extended half-life type antibodies. I guess, how would you frame, you know, how you're thinking about differentiation versus those other TSLP programs? Is it about dosing? Is it about, you know, potential better efficacy? How would you kind of compare and contrast? Yeah, I think, I mean, the first point that we always make is that our approach to modulating TSLP is different and unique. Everybody else is targeting the ligand. We do think that that confers meaningfully different pharmacology. And, you know, I won't restate everything. I just, yeah. But, you know, the way that we get to extended dosing is through potency, not through Fc Engineering. I think what we're seeing with the programs that have ligand-targeting, YT-modified, anti-TSLP antibodies is that it's early days. Yep. And that there are a number of questions about how you get, you know, what are you going to sort of make as your line in the sand? Is it going to be dosing interval or is it going to be efficacy? And then once you choose one of those, you know, how does the other follow? I think we've seen some evidence from example of YT, IL-5, where, you know, the six-month dosing interval was met in clinical trials, but, you know, there may be some waning of efficacy over time. we've seen other companies recently reading out data that suggests that, you know, you can have extended dosing interval, but it very much matters what sort of, therapeutic efficacy level you want to see. And it's going to be basic pharmacology that governs, you know, the trade-off between efficacy and durability. What we have learned is that people are not interested in trading off efficacy for durability. I think, you know, the winners here are going to have great efficacy, durable efficacy at a dose that can be in a dose, you know, sort of presentation that can be reasonably delivered, do it safely, and that we still have a lot to learn from these programs, whereas we're reading out placebo-controlled phase II data. You know, and to your point around EC90 coverage and the data that you generate in the phase I-b in asthma and CRSwNP, I guess, is there a path for you to really drive towards differentiated efficacy based on what we have? Is that, is that open at this point? Yeah, I mean, I think Is that needed? I, again, you need at least, I think, class meeting efficacy. It would be nice to have class beating. You know, you can, we can have a debate about whether or not what we saw in our nasal polyp study was better than tezepelumab. I think if you apply, you know, a less stringent statistical analysis, we were numerically better. Do I think that that met the meaningful clinically important difference? Probably not. but look, let's see what happens in severe asthma. I showed you the pharmacology modeling data that suggested that we could have a greater effect on FeNO in severe asthma. We do think that that's highly translatable. But, you know, for our initial readout here in severe asthma, we're looking at a 50% reduction in asthma exacerbations as what would be competitive if we can deliver that at Q12 or Q24 weeks. Yeah. That, that's really my next question. Your data in the first quarter framing up what you want to see to then really be excited about moving into phase III. Yeah. I mean, that's what we would like to see. I think that's a really good and really competitive profile because of the substantial extension or reduction in the dosing interval. If we can deliver greater efficacy, great. And we'll see soon. I think in terms of what phase III looks like, you know, that's going to be dependent on a lot of things. We're fortunate that we had been executing so well that we were able to substantially pull up the timeline for our asthma data such that we now have in hand almost contemporaneously data from CRSwNP and severe asthma, a couple of different diseases, a couple of different patient populations, several different dose regimens. We're going to learn a lot more about the molecule and its pharmacology. We're going to take that as quickly as we can to regulators in terms of phase III design. You know, hopefully be able to choose a dose that really gives us a very strong hope of differentiated efficacy and convenience. On the execution front, you know, you've obviously accelerated timelines. How is the level of competition among sites in the U.S. and globally right now? Yeah, it's definitely non-zero. You know, it's competitive out there. I mean, our team works very hard out there with sites to really, you know, be competitive. We've also been fortunate that, you know, as we move into COPD, a lot of those are the same sites that work with us in asthma, and there's been a ton of enthusiasm for the molecule. You know, we're pretty humble about the competition, and we bake all of that in in terms of our forecasts, but we've been very pleased with the way that the COPD trial has begun to enroll. You know, we hope for that momentum to continue. I think, you know, the other thing about the competitive landscape is just to note that we think that we are well ahead of other competitors in terms of where we are in our execution and in the quality and magnitude and significance of the data that we are generating and presenting. You know, the timeline advantage is non-trivial. It comes from execution. Yeah. These trials require many, many, many months of observation. It is very hard for folks to catch up. I think it's always the question for biotechs going after these large markets, but is there a path for you to go this alone commercially? How do you think about partnership? When would that make sense? Or is there a path for you to actually launch a drug in asthma, CRSwNP and maybe COPD by yourselves? Yeah. We do not trivialize the challenge of commercializing a molecule in these markets. There are some very big, very experienced competitors out there who we respect. Having said that, we think that the greatest value for Upstream Bio shareholders is to develop verekitug ourselves and retain as much of the value ourselves. We are definitely well staffed and resourced to, you know, get these drugs. We'll need more resources, but, you know, certainly well staffed to get these drugs to approval. How we go about commercialization, I mean, we look at Verona as an example of a successful independent commercialization story recently in our space. And outcome. We, you know, we do know, I mean, these are not new diseases and not necessarily novel commercial approaches either. We know where the patients are. We know what the paradigms are. We know where the physicians are. We know the differentiation matters. If we can bring all of that, there is a potential path for us to do this ourselves. Maybe last question, you know, runway through 2027, what is embedded in those assumptions in terms of trial execution, et cetera? Yeah. The 2027 funding gets us obviously through our nasal polyps data. It'll get us through our severe asthma data. It'll get us well along into COPD. It's enabled substantial phase III preparation activities, and it's also enabled substantial investments both in CMC and device. Our hope is to launch our product in an auto injector. And, you know, that takes substantial resources, and we're investing in that today. Great. Any, any other questions? Great. Rand, thank you. Appreciate it. Thank you, Alex. Appreciate it.