Okay. Well, good morning, everybody, thank you once again for joining us for the 46th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the biotech team, along with my colleague, Jaena Han. It's a great pleasure to moderate the next fireside chat with Upstream Bio. With us today really needs no introduction, Rand Sutherland, CEO. Rand, thanks for joining. We appreciate it.
Yaron, thanks for having us. Really appreciate the opportunity.
We're gonna do our pulmonary panel, I believe, later today. It's weird that you're not sitting on the panel as a KOL, which what we're used to in many ways. Lots to discuss on the heels of your phase II VALIANT data for verekitug, which was released just about a month ago or so, long-acting TSLP. This was a sizable study, met the primary endpoints both in Q12W and Q24W, showing a 56% reduction in relapse with a 100 mg Q12W and 39% reduction with a 400 mg at Q24W. There's a lot to talk about and unpack in the data, but largely the data was more or less in line with Teze.
Remember, Teze is monthly, showed a 56% reduction. Again, the Q12W was essentially identical. There's a lot to unpack on even the FEV1 data and the FeNO data. Maybe to zoom out and as you look at the data and the consistency that you're looking for, and when we talk to physicians, they continuously tell us Q12W is where they wanna go. That's how the case of patients coming in, and they're not willing to sacrifice much efficacy on endpoints in favor of durability. To them, the difference between Q12W and Q24W is not that high. When you look at the totality of the data, in some ways, Q24W looked very, very convincing as well. In terms of overall consistency, how do you look at the data?
Yeah. First, we're thrilled with the data. I mean, they continue the story about verekitug, its potency, and how that potency translates to really great efficacy at extended dosing intervals. You know, the fact that with Q12W dosing, our, you know, highest dose of 100 milligrams Q12W delivered a 56% reduction in asthma exacerbations, that was statistically significant, along with, you know, numerically quite substantial improvements in lung function and reductions in exhaled nitric oxide. That's a great profile. That's the profile we had, you know, been talking about as really being sort of our base case. That base case, although base case can mean a lot of things, in our case, that is a, you know, best-in-class meeting type of efficacy profile delivered with quarterly dosing. You know, the potency profile of verekitug is again reinforced.
You get to spend that potency in two ways. The first is sort of magnitude of effect, and the second is, you know, dosing interval. I think we've shown that, you know, with that particular dose regimen, we've, you know, really had a very solid outcome. Now, to your point, actually, when we look across the medium dose and the low dose regimens, 400 mg Q24W and 100 mg Q24W, respectively, we see statistically significant reductions in asthma exacerbations. In the medium dose, we also see substantial improvements in lung function in FeNO. With the lower dose, we start to see, you know, some of that impact, particularly in lung function and biomarker suppression fall off. There is, you know, as one would expect, dose ordering here.
We're in a position now where we can take all of these data, do very robust sort of exposure-response modeling, and really understand as we go into phase III, again, how do we wanna spend this potency, what is our path to greatest efficacy, and whether we deliver that great efficacy at quarterly dosing or twice-a-year dosing, that's gonna be a substantial advance in the field. That's the work we're doing. We're doing it as quickly as possible. We know people wanna hear what's next. We hope to be able to communicate on that here in the upcoming weeks. We're in a very fortunate position. We have great data now from two phase II trials, placebo-controlled in two major Type 2 indications. This, we believe, is a potential medicine. We have $341 million in the bank.
We are able to go heads down and get the work done.
When we look at the data overall on FeNO and FEV1, they're essentially identical, Q12 and Q24. It's just on AAER is where you saw a difference. By the way, the lowest dose on AAER actually looked very good. Even, it's really the medium dose in Q24W is the one that had a little bit of that decrement. It looks like there was variability in AAER. What, what drives that?
I think we have to think about AAER, asthma exacerbations, in a different way that we think about FEV1 and FeNO. You know, FEV1, continuous variable, you can measure it frequently over the course of a trial. Exhaled nitric oxide, continuous variable, you can measure it frequently over the course of a trial. We treat asthma exacerbations as a continuous variable in our analyses, you know, to your point, they are to some extent random or stochastic type of event. You need a certain underlying degree of airway inflammation to have an exacerbation, often you'll need a second hit, like a virus or an allergen or a pollutant or something like that. They are more variable by nature. They are dependent on, I would say that inflammation is necessary but not sufficient.
You know, it's a little bit different in how you can interpret these. It's, you know, then plays itself out, particularly in smaller phase II trials with a little bit of variability in terms of, you know, where you end up at any given point. Now, you know, again, we feel that the data are very strong. Actually, if you plot the point estimates and the confidence, you know, bounds on top of each other, they all essentially overlap. This drug is efficacious at improving asthma exacerbations. It's efficacious at improving lung function and airway inflammation. Our job now is to, again, find a path to the highest degree of efficacy with extended dosing, whether that's quarterly or twice yearly.
I would say that our experience, our clinical judgment, our sort of informal and maybe qualitative interactions with patients, physicians, and payers, and our quantitative market research all reinforce what you said at the beginning. Efficacy is king. Six months is great, but people are not willing to make any trade-off of efficacy for convenience, if you will. We need to develop, you know, a molecule that has robust, almost bulletproof efficacy. We want that efficacy to be as good or better than anything else out there. Again, if we can deliver that with quarterly dosing, we've got a great medicine.
When you look at the data, I mean, the data's so rich. You've shown us data by subgroups, you've shown us data by global distribution. The study wasn't powered to detect TH1 versus TH2 activity. I think some investors were hoping to see, you know, I'm sorry, yeah, what I meant TH2-high-
Yeah.
... T, TH2-low. In one of the subsets, I think, investors wanted to see maybe a little bit more clarity on the TH2-low. We've got a lot of inbounds on that. Is there any way you can comment on that subset?
Sure. You know, I think there are a number of ways of thinking about this. I mean, the first is that let's just look at that particular subset. To your point, we were not powered to detect differences, you know, in these subsets in this trial. You know, we do see when we look at the forest plots that there's a greater degree of efficacy in the high eosinophil population versus the low. That's the biology. That's what all of these biologics have shown to be the case. It would be a surprise if we didn't show that here, and in fact, we did. Now what is also known about biology is that the biology of TSLP is such that, you know, tezepelumab, you know, has impact in the lower Type 2 inflammatory population.
We don't think that that biology is any different if it's being prosecuted by verekitug versus tezepelumab, and there's no reason to believe, based on what we know about the biology, that targeting the receptor versus the ligand should have any differential effect. Why did we see what we saw and what are we gonna do to convince ourselves and, you know, importantly regulators, physicians, patients, that there is this degree of broad efficacy? Well, the first is we need to push the dose as high as we can. You know, we've got a lot of exposure data with this drug. One of the things that is unique about verekitug in the competitive landscape is that we have hundreds and hundreds and hundreds of patients' worth of data now to work with across multiple placebo-controlled trials and two Type 2 indications.
You know, that's a pretty unique position to be in. We need to choose a dose that delivers the greatest efficacy, and we need to start to pull some design levers as we get into phase III to be sure that, you know, we really have a population that has a high signal against which to work. Why do I say that? Well, one of the things that drove what we saw in the low EOS population is that the exacerbation rate in placebo there was like 0.7. Very, very low, amongst the lowest ever reported, and so low that it's really hard to improve upon. Now, on the flip side, if you look at the high EOS population, actually our efficacy there is 80%+, which is.
Mm.
... some of, if not the highest efficacy in that population that's ever been reported. Again, the underlying biology is playing out here. We're seeing that those patients who have the greatest degree of Type 2 inflammation are having the greatest response. For us to be able to develop this drug in a broad population, we're going to need to, you know, make sure that we've got an exacerbation signal in that group. We're going to need to, you know, pull some other things to do that we can along the way to make sure that we've got a signal there that verekitug can work against.
In terms of further analysis from the data, what else are you planning on looking at?
The first thing that we're doing, we're doing this all now, and it's, you know, actually quite complicated PK/PD work. It takes a lot of time. It's very sophisticated. We have a ton of data. It requires a lot of computing, you know, resources to do this. You know, the first thing is understanding, okay, did we end up now at the end of VALIANT where we thought we would be in terms of exposure? Our thesis all along has been that because we have such a potent molecule, we can keep drug concentrations well above important thresholds, like say an EC50 or an EC90 for exhaled nitric oxide. We wanna convince ourselves that we continue to do that.
We wanna quantitate the level of exposure that we end up with in these different dose regimens, and then we wanna be able to compare those exposure thresholds with the competition, in particular tezepelumab, because we think a path to greater efficacy could be greater exposure. That's one thing that we're doing. The second thing that we're doing is that we are working through then the relationship between exposure and response. Again, we wanna push efficacy as high as possible. The way that we think we can do that is by delivering, you know, a maximal dose. Again, if we can deliver that great efficacy at quarterly dosing, that's a great outcome. That's a differentiated product in our view, and it's one that is going to have a significant impact on care. We're doing those sort of two work streams in parallel now.
We've already started at risk, you know, the regulatory briefing books preparation. We've started actually phase III design-
Mm-hmm
... and some of the operational elements at risk. We are well prepared to stick on our timeline, which is, you know, have these trials both in severe asthma and CRSwNP, hopefully up and running by the end of this year, early next, and get, you know, to quickly prosecuting these phase III programs. Time is important here. You know, we do there believe that there's a path to be potentially still the second long-acting drug to market, in severe asthma and potentially the first in CRSwNP, and that's a great position to be in, particularly with this kind of profile.
It sounds like, first of all, have you decided whether it's Q12 or Q24?
The work that I just described will inform that decision.
It sounds like you're contemplating potentially going higher, 'cause certainly, I mean, you have data covering 400. The data that worked, you know, best Q 12 is 100 obviously. That was the no-miss dose. You can even go higher if you go Q12 .
Potentially. I mean, you know, the greatest sort of the bookends of the greatest amount of exposure range between 100 mg and 400 mg. Of course, in phase I we generated more exposure than that. Yes, we have a range here to work with, and that's exactly what we're looking at. Again, you know, we view it almost as defensive to try to, you know, deliver a Q six-month profile solely because others may deliver something there, whereas we can be offensive with a really robust profile, potentially the greatest efficacy at quarterly dosing. Again, our view is that that's what we have to deliver above all else.
Is phase III gonna have a single dose or II doses?
I think it's most likely it's gonna have a single dose. You know, you're already talking about maybe a 1,000-patient trial with one dose versus placebo. You know, to prosecute two doses would be substantial investment with delayed timelines and increased costs.
Would it be the same dose for both CRS and asthma?
I think our ambition would be to take the same dose forward in both, and potentially in all three indications.
Okay. Any questions from the audience? Can you maybe talk about, you know, one of the questions that we're getting for a long time is you're the only TSLP targeting the receptor?
Right.
The concerns historically were ADCC and safety and in general, there were some questions about ADAs.
Mm-hmm.
Can you maybe address all of that with what you saw at the data?
Maybe I'll start with safety because that's the thing that all of this plays into. You know, the safety profile of verekitug is so far quite good. I'd say it's consistent with other biologics in the space. We have, you know, a very clean safety profile. You know, we did report an ADAs prevalence of around 50%-60%. That's very in line with what we observed in phase I, and, you know, we've published those data as well. You know, it's perhaps not surprising that we have ADAs. You know, the TSLP receptor is a cell surface receptor. It's expressed, for example, on dendritic cells. You know, we do observe ADAs. We also observe that the great efficacy that we've delivered both in CRSwNP and severe asthma is net of any impact of ADAs on exposure.
We're doing the work now to really understand that ADAs. You know, we include ADAs basically as a covariate in the exposure models. You know, we will see where we land. You know, we could not have delivered this great efficacy if ADAs were really causing a significant reduction in exposure. We'll be able to be more precise about that, you know, when we communicate next steps. I think we're in a good position to move forward again in ways that we've talked about.
Do you have a sense on the temporal relationship between ADAs and exposure to the drug? Is it increasing? Is it stable? Is it decreasing as it gets sensitized?
Yeah. We're in the early days of exploring this. In general, the ADAs, you know, are not present at baseline. They are present after the first dose. In general, our experience thus far is that they do not continue to increase. They are, you know, largely stable, maybe in some cases declining a little bit.
This molecule was developed by Regeneron. It's fully human.
Yeah, it depends how you define developed. Astellas actually developed the molecule and they discovered it using Regeneron's platform technology. It's a product of the VelocImmune platform. It's a fully human IgG1. Doesn't have anything done to it to extend the half-life. Again, all of the, you know, efficacy that we see and all the sort of ability to dose this at extended dosing intervals is purely driven by the potency of the molecule.
There's no signs of neutralization to your point?
We have assays that measure the sort of overall titer of ADAs and of neutralization. I'm not an expert in this field. In general, ADA titers are perhaps more of a manageable proxy for neutralization and more easily included, for example, in PK/PD models. We are looking at both. I don't have all the data, you know, with me today. This is something that we'll be communicating on. Again, no effects on safety. All the efficacy that we've delivered thus far is net of ADAs, and we will be very clear to understand the relationship of ADAs to exposure when we go to make dose selection for phase III.
Okay. maybe before I pass it to Jaena on CRS, in terms of the manufacturing and actual device presentation...
Yes.
Give us, maybe an update on where you are in that.
Sure. You know, Upstream has been very aggressive about, you know, CMC development, device development, throughout its history. You know, we want to be able to launch with a phase III formulation that doesn't need more work. We want to be able to launch with an auto-injector, and we are well on the way to do that. I would say that along the way, and this is important again in the competitive landscape, we've developed a very concentrated formulation of 200 mg/ mL. That allows us to give our highest dose of 400 mg in one single two cc injector, injection. That makes it very compatible with commercially available auto-injector platforms.
We do think, you know, the pharmacology challenge that everybody in this space has to thread is, how can I give enough of a molecule to have coverage over an extended period of time? You know, when you start to get to the 500 mg, 750 mg, 1,000 mg level there to get six months coverage, you know, you really need types of formulations or drug device combinations that, you know, maybe are different than the approach that we're taking.
Okay.
Great. I also want to talk about your previous data in CRS with NP as well. Obviously, you had the phase II readout earlier. Verekitug showed significant benefit on both the primary endpoint of NPS as well as the secondary endpoints, including NCS and risk reduction in the need for steroids or surgery. I think over this weekend, you actually presented a new analysis that used a slightly different analysis that accounts for concurrent use of steroids.
Yes.
Could you walk us through how that changes your data...
Sure.
How the new efficacy profile might compare with tezepelumab and dupilumab?
Sure. We're gonna get hyper-technical here in a minute. Maybe I'll start by just, you know, reminding everybody of what you just said, which is that verekitug delivered in our phase II placebo-controlled trial of 100 mg Q12W versus placebo in CRSwNP, outstanding efficacy. I think efficacy that's as good as anything else out there, and again, at quarterly dosing. The primary endpoint, as you mentioned, is an endoscopic nasal polyp score. We also look at symptom indices. We actually look at CT scan measures of sort of Nature and extent of sinus inflammation, and we even looked at, you know, a very clinically important endpoint of need for rescue therapy. In this disease, rescue therapy is either a systemic corticosteroid or surgery.
Now, to your question, what happens in the analysis of these trials because the frequency of utilization of steroids and surgery is so much higher in the placebo group, if you don't do something to basically eliminate the quote unquote pollution of that positive effect on the placebo arm, you can find yourself in a situation where at the end of the analysis, placebo looks better than it actually was, and that sort of betterness is driven by actually the use of steroids and surgery. You know, the approach that lands you there is called a treatment policy approach. We took that approach in our phase II trial because that's what FDA guidance recommends.
We wanted to take, you know, that type of approach because we are leveraging here a sort of phase II, phase III sort of pivotable package in both indications in our, in our regulatory negotiations. You know, that gave us the efficacy that we saw, and, you know, really substantial improvements in the endoscopic nasal polyp score that really pretty much met that of Teze, maybe a little bit better than Dupixent. When you don't use that treatment policy approach and you do something called worst observation carry forward, you basically, you know, stop the clinical endpoint measurement at the time of the administration of that rescue therapy. You sort of then remove any contribution of that rescue therapy to the endpoint in the placebo group.
When you do that, and these are data that we've just presented at AAAAI this weekend, you get, you know, a maybe a 0.1 or a 0.2 further improvement in the endoscopic nasal polyp score. While that does give us numerically the largest effect that's been reported, you know, I think it'd be a little bit too much to say that, you know, it exceeded some minimal clinically important difference or something like that. I think where we end up is, look, the profile of the molecule is great. It delivers outstanding efficacy. It does so with quarterly dosing. We believe that that profile is tremendously valuable. Again, we think that same profile has been reiterated now in both of these clinical programs.
Right. I know we shouldn't do cross trial comparisons, but when we do, how were the other trials for Dupixent, Tezspire analyzed in terms of, you know, did they use this worst observation carry forward? Did they account for steroid use currently?
Yeah. Well, I think you can answer that question by looking at Tezspire's phase III publication in the New England Journal. Look at the point estimate that's reported there, and then look at the point estimate that's reported in the label. They are slightly different. They're slightly different in the direction that you would expect based on what I just described. you know, it's look, Tezspire has great efficacy in CRSwNP, but yes, these nuances of statistical approach do make a difference. you know, you need to look at the totality of the evidence, I think, to demonstrate compelling differentiation, you know, a small difference in the primary endpoint versus sort of the overall, you know, the way that the profile looks, the dosing interval, and, you know, again, across multiple indications.
You know, that's how we sort of see the weight of evidence being built here and being most strong.
Right. Then initially when we looked at your data set, there was some concern that maybe there was a higher enrollment of high EOS patients that might have driven some of the efficacy benefit. Kind of how should we think about that?
Yeah. I guess I would discount that a little bit only because CRSwNP is not severe asthma. you know, probably of all the indications that we're testing, CRSwNP is the most robustly Type 2. you know, you know, systemic inflammation, Type 2 systemic inflammation is reflected to some extent by the EOS count. this is a case where it's so robustly Type 2 and where there's such, you know, local inflammation that I don't think our results can be explained solely by that.
Right. That makes a lot of sense. In terms of a key secondary endpoint that we touched on before, verekitug also showed a 76% risk reduction in the proportion of patients that require this kind of rescue medications.
Yeah.
How important is this for kind of patients and physicians as opposed to the primary endpoint?
Yeah. I mean, we think it's very important. I think from a payer perspective, you know, it's these types of events that, you know, you have to go see a doctor to get your steroid prescription. Obviously, you have to see a doctor to get surgery. You know, this was a big part of the reception of tezepelumab CRS data, and we were not powered to show this, but we did. I think it was a really great outcome. Yes, you know, just because of the relative frequency of these two approaches, more patients end up getting steroids or not getting steroids than surgery, but used as an aggregate measure of the need for rescue therapy, it's a very important endpoint. That's certainly something we would hope to recapitulate in phase III .
Right. Phase III, do you think that you'll report this outcome a little bit more similar to how Tezspire reported it? I know it was a little bit different in terms of you report it as a percent of patients requiring surgery, whereas I think in the Tezspire and Dupixent trials, it was kind of the time to next surgery.
Yeah. I mean, I think we would anticipate doing both. I mean, you can use the data and report those outcomes in both ways.
Great. They're typically tightly correlated, so we should expect kind of similar magnitude of effect.
In terms of time to versus proportion?
In terms of kind of-
Just phase II to phase III?
Type 2 versus proportion. When you look at it in a different way, you still see the same kind of...
Yeah. I think they're different measurements. You know, the proportion probably at the end of the day, given the relative infrequency, particularly of surgery, is maybe a little bit more clinically meaningful. I mean, we would wanna demonstrate efficacy in both of the analyses.
Right. That'll be exciting. I do wanna touch on COPD in the last five minutes.
Sure.
You are. This is kind of your third indication. You're evaluating it, verekitug in the phase II VALIANT trial with 666 patients. I think the first patient was dosed in July of last year, and you're now, I think the last we heard, over 60% enrolled in this study.
Yes.
Kind of question on timing. Do you think you can finish enrolling maybe by the middle of this year? Given that it's maybe a one-year study, can we expect data maybe around second half of next year, optimistically?
Yeah. I think, particularly in light of what we've just learned from asthma, you know, we need to really think pretty deeply about what, if any, implications there are on what we've learned and what decisions we make about phase III in light of the COPD trial. You know, for that reason, we've been a little bit circumspect about leaning in on timing, particularly now. You know, the ambition there is to still, you know, as it is with all the other indications, deliver a great drug for patients with COPD with the highest efficacy. You know, as you'll recall, the phase II trial that Teze did sort of as a proof of concept in COPD, showed a nice impact on the reduction of COPD exacerbations in patients with EOS 150 and up.
For that reason, we actually designed our trial to have the primary analysis in that EOS 150 and up subset. you know, we still continue to believe that the two dose regimens that we're testing, which are the high and the medium doses, you know, same regimens from our asthma trial, could be efficacious if we, for example, take a different dose forward in phase III in severe asthma, we may wanna make some changes to the COPD trial. What those changes look like at this point are speculative. you know, I think we just need to have that out there as something that the company is thinking through as well. Now, having said all that, as you say, enrollment's doing great.
You know, we are ahead of predicted timelines there, and so I think that accelerates things beyond what we might have originally thought, but may be a little too early to put an exact number on when we would expect data.
Right. kind of reading between the lines, potential to, if you decide on a different kind of higher intensity Q1 2W dosing for asthma, maybe you could replace the Q 24W just so that the COPD trial has maybe a more relevant dose.
Right.
Is kind of a reasonable think about?
Yeah. Replace, add, other.
Okay.
Right. 'Cause that's a sizable study. That's supportive of the label of a future phase III.
For sure. I mean, again, subject to regulatory negotiations, but that's the ambition.
Right. Would be well worth it.
Is there any reason mechanistically when we look at COPD as an indication that you expect that you might have a different dose in COPD versus asthma and CRSwNP, and kind of what goes into informing that decision?
Yeah, I mean, again, the biology that we're mostly trying to, you know, abrogate here is Type 2 inflammation. You know, patients with COPD are probably, you know, depending on the subgroup, the least Type 2 in aggregate. You really have to focus on a group that's enriched for Type 2. That's why these EOS of 150 and up are sort of an ideal population for that. Again, this same sort of continuous response of degree of efficacy versus degree of Type 2 inflammation has borne out in the Dupi trials and in Teze we think thus far in COPD. We would wanna continue to leverage that. Now, you know, yes, potentially pushing even a higher efficacy path forward could deliver greater efficacy. Again, that's a hypothesis that we need to test.
I would say that of all of these indications in aggregate across all of these drugs, COPD is where the dataset is the least rich. You know, we'll also be looking at our data very closely, and if there's an opportunity as we make these changes to, you know, have an early look at those data, that could be informative as well.
Right. As we think about all three indications that you have going with asthma, CRSwNP, COPD, and you know that some of them maybe have more competition from other TSLP agents, how are you thinking about the opportunity for verekitug in each of these?
Yeah. You know, obviously we have competition from tezepelumab because it's on the market and it's doing great. You know, the what's gonna happen with all the other programs, including ours, you know, needs to be further refined with data. I think that Upstream Bio is in a great position with a very robust data set, as I've mentioned, going into phase II negotiations with the FDA to understand the pharmacology of our molecule, to have, you know, the approach to phase III be as absolutely de-risked as possible. As I mentioned, we think if we move quickly, we can still have a timeline advantage as well.
We don't want to give up any of that. We're gonna work as quickly and as hard as we can to stay, you know, on our path to phase III and in CRS with MP and severe asthma. Because, you know, as Yaron mentioned, the COPD trial is so large and is, you know, a 52-week follow-up period, you know, we have time there to, you know, to if we need to make any changes and still, you know, not have potentially those timelines lag excessively.
Can I maybe ask a philosophical question? This has become an area of competition. Some of the other companies that are behind are jumping over phase II. They're taking risk. They're using PK modeling, and sometimes they're using CDR expression of a competing data of a drug to then, you know, analyze their data and make assumptions on their PK. To your point on with COPD, you know, as you fine tune and decide, does it make sense to perhaps go a little bit at risk and change the trial design, pick a dose, and make that into a pivotal even?
You know, you asked and you posed it as a philosophical question. For us, it's a very, you know, important non-philosophical question, right? I mean, the first is pharmacology is not philosophy. You know, there's a reason that drugs are developed this way. You know, you're seeing in the Upstream experience, the experience that of others have had, where you learn and you know, kind of not course correct, but maybe course alter based on your understanding of the molecule, and you go into phase III knowing as much as you can possibly know. I think if you don't do that, yes, you are taking substantial risk. You know, what we do with COPD or any of these trials, I mean, you know, there's some at risk you can take, but there's also a pretty clear regulatory path.
People love to ask, "Okay, what do you think about the FDA stance on single trials, et cetera?" you know, I think our view is that it's been the case a long time in respiratory disease that a single phase III can augment a phase II and be the basis for approval. We don't see that changing.
Mm.
You know, that's the path that we would, I think, wanna prosecute here. We do need robust data from any indication, including COPD, to submit a BLA.
Yeah. Great. Well, I know we're over. Ran, thank you so much for joining. We appreciate it.
Thank you, Yaron.
It's good to see you.
Appreciate it.
Thank you.