Ladies and gentlemen, thank you for standing by, and welcome to the Connect Biopharma conference call. At this time, all participants are on a listen- only mode. After the speaker's presentation, there will be a question- and- answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to David Szekeres, President of Connect Biopharma. Please go ahead. Thank you, operator. Good morning, everyone, and thank you for joining us. With me today from Connect are Barry Quart, Chief Executive Officer and Director, and Kimberly Manhard, Executive Vice President, Chief Development Officer. For those of you participating via conference call, the slides are made available via webcast and can be accessed by going to the investor relations page of our website following the conclusion of today's call. Before we begin, I would like to remind you that this call will contain forward-looking statements under applicable securities laws. These statements involve substantial risks and uncertainties and include statements concerning Connect's future expectations, plans, prospects, corporate strategy, and performance, including with respect to research and development programs, clinical trial plans and results, regulatory strategy, timing and approvals, market research, assumptions and projections, cash runway, and anticipated catalyst milestones. Actual results may differ materially from those indicated by these forward-looking statements due to various important factors, including those discussed in this safe harbor slide, the press releases issued by the company today, and our filings with the SEC. Forward-looking statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update these statements. Now, I'll turn the call over to Barry. Thank you, David. Welcome, everyone, to the call. We are extremely excited to have this opportunity to provide two important updates on the development of rademikibart, a highly differentiated IL-4 receptor alpha monoclonal antibody designed by Connect. We will be reviewing this morning preliminary top-line results from our IV clinical pharmacology study of rademikibart in asthma and COPD patients, and phase III atopic dermatitis results presented Saturday morning in a late-breaker session at the American Academy of Dermatology Conference. Before the data, I will quickly review the differences in biology that make rademikibart remarkably different from other drugs in the category and ideally suited to treat both acute exacerbations of asthma and COPD and chronic management of these diseases. After the presentation, we'll be happy to answer questions. The biology of IL-4 receptor alpha obviously is very well known and an ideal target for multiple diseases. The components that make rademikibart unique and highly differentiated, first and foremost is the faster onset of the product, which was identified in a prior chronic asthma study. We'll go through some of that data and identify for you really what is the very intriguing biology behind that. We also see substantially greater responses in terms of FEV1 in asthma patients. We've demonstrated in atopic dermatitis that the product works Q4 weeks, so as compared to dupilumab, a more convenient dosing option. We had noticed early on a reduction in eosinophils versus the increase observed with dupilumab. That led us to understanding some of the significant biology differences of the products. The differences stem from a completely different binding orientation of rademikibart versus dupilumab. We bind at a different epitope. The tightness of the binding is substantially greater than with dupilumab. Because of these differences, we see significant differences in internalization, which results in significant differences in the observations in the clinic. Go to the next slide. What we'll be talking about is differences in eosinophils, as I previously mentioned. We have information that was generated in human airway smooth muscle cells and human precision-cut lung slice data. Initially, the differences between rademikibart and dupilumab were noted in the clinic with the observation of decreasing eosinophils in the chronic asthma study that was previously conducted. This was a surprising observation. Considering that dupilumab is well known to increase eosinophils, and in some case, quite substantially. This is not just a lab observation. We see here hundreds of serious adverse event reports submitted to the FDA for dupilumab in asthma patients related specifically to increased eosinophils. We spent significant time trying to understand this very different profile. Ultimately, we determined that the likely origin of this difference is substantially greater internalization of the rademikibart receptor complex. This substantially greater internalization results in greater turnover of eosinophils, which would certainly explain the decrease in eosinophils versus the increase. Because we have significantly enhanced internalization of the complex, we also would be removing receptors from the cell surface. That may play a role in the fact that we see such excellent activity at Q4 weeks in AD, where dupilumab was unable to demonstrate good activity Q4 weeks. The other associated potential benefit of decreasing eosinophils is that I'll be showing you clinical data that demonstrates we see really no significant increase in conjunctivitis versus the 10% conjunctivitis seen with dupilumab in early 16-week studies, and even higher rates over time. Now we consistently see low rates of conjunctivitis really not differentiated from placebo. We'll go now into some very intriguing data, collected in preclinical models, specifically looking at airway function. It's well understood that IL-13 and IL-4, but particularly IL-13, has direct effect on airway smooth muscle, and has been shown to shift the dose response curve of beta agonists. We spent significant time looking at the biology of how beta agonists produce relaxation in human airway cells, to see if that understanding that pathway would give us a clue as to the differences in biology. The right panel here in the graphic, this is looking at human smooth muscle airway cells. And specifically looking at phosphorylated HSP20, which is a marker of relaxation. It was downstream on the prior schematic. You can see that in the cell culture, addition of rademikibart significantly increased that marker of relaxation, whether it be alone or in the presence of the inflammatory cytokines, and a very different presentation than what was observed with dupilumab. To go further, we went into human precision-cut lung slice model. Here we see the classic shift in the dose-response curve of formoterol, a potent beta agonist, making that drug less effective in the presence of the inflammatory cytokines for bronchodilation. When we add rademikibart, we see that and we get an improvement in bronchodilation and move the curve back towards a baseline. But very interesting, w hen we add dupilumab to this experiment, we see no effect. This is not simply binding to the receptor and blocking attachment of the inflammatory cytokines. This is through a secondary biology, probably similar to what was seen in the human airway cell, increasing phosphorylation of HSP20. Because this was such a surprising observation, we went to another lab that has a significant experience in doing precision-cut lung slice work. T his is even larger number of samples, was able to reproduce the observation where there was no effect of dupilumab on the reduction in the benefit of the bronchodilator, but a significant improvement with rademikibart. Based on the rapid onset of FEV1 increases that was seen in the original chronic asthma study, current development of rademikibart is focused on treatment of acute exacerbations in asthma and COPD. Ultimately, the goal would be to have both acute and chronic indications, but we've put our current focus on demonstrating a benefit in the acute setting. I won't go through all of the details underlying asthma and COPD, but the most important focus of this discussion is the large numbers of patients going to the hospital for acute exacerbations. Over 1 million ED visits for asthma patients, 1.3 million for COPD patients. That's really the tip of the iceberg because we see with that 1 million patients, asthma patients going to emergency departments, there's even more patients going to urgent care or doctor's clinics to get treatment for the acute exacerbation. Very similar numbers in Europe. This is clearly a global issue. Again, the information on the speed of onset came from original phase II-B chronic asthma study, fairly straightforward design. Next slide shows the FEV1 improvements in that study. Because we collected information starting at one week in the clinic, it really spurred our interest in how fast their drug was working because by one week, we already saw a very significant improvement in FEV1, almost 250 mL on average. By drilling in further into home spirometry, we found that the majority of this benefit was observed the morning after a dose. In less than 24 hours, we were seeing significant improvement in FEV1, much faster than what would be anticipated from a biologic. This just helps to put the significant improvement in FEV1 into perspective versus other biologics. As you can see on the far right, when we look kind of as close to apples to apples as we can across study, patients with greater than 300 eosinophils, we see certainly a what appears to be the greatest magnitude of improvement with rademikibart compared to other biologics, including dupilumab. With that information on the very rapid onset of effect from the chronic study, which was conducted with subcutaneous administration of rademikibart, we set out to initiate phase II trials to see if we could demonstrate a benefit in patients having an acute exacerbation. In parallel, we started to evaluate the opportunity to potentially use IV administration to speed up the onset even more. What we'll be sharing with you today is, for the first time as I mentioned, preliminary top-line results from the IV study. The IV study, what we'll be talking about is Part A and Part B. Part A was healthy volunteers. We had very little information on IV dosing. The first question is, can it be done safely and more quickly than the 30-minute infusion that was initially tested back in the initial development of rademikibart? In that Part A session, we found that a two-minute IV push was very well tolerated, no different than slower administration with similar PK. We chose that to move forward into the patient component of this study, where we were evaluating stable asthma patients and COPD patients to see whether or not the improvement in FEV1 could be accelerated. This slide describes some of the entry criteria. Next slide shows the baseline characteristics of the patients that were enrolled in the study. I think that the most important observations here is a high percentage of smokers. These are difficult patients to treat in general. Eosinophil lower limit was 200 in order to make sure that we were selecting patients with a T2-mediated disease. We wanted to have as close to real-world data as we could, so we set that bar fairly low. In fact, the majority of patients were 200-250, so right at that entry criteria, even though the means are about 330. Finally, FeNO, while we would love to have patients with greater than 25 FeNO, in order to really pre-select patients that will do very well on this mechanism, because of the high proportion of smokers, FeNO in this case was really not predictive of how much airway inflammation patients had. Smoking has been shown to decrease FeNO. Here we have the top-line preliminary results looking at change from baseline in placebo-corrected FEV1. You can see here that we have immediate effect at 15 minutes in terms of improvement in airway function. It bounces around some. This is a small study of 12 patients, two placebo, 10 active. Certainly by three, four hours, we see a stable improvement in the 200-250 range, which is, as you recall, from the chronic asthma study, what we achieved, at least in the clinic, at one week and with home spirometry in a couple days. Here we're shifting that now to several hours. Certainly by the end of the first day, we are now in the 200-300 mL improvement territory, and we continue to maintain that through 29 days. All of these data points are pre-bronchodilator. Bronchodilators were withheld for the first day in order to get the cleanest data of what rademikibart does on its own. You see two data points that were collected post-bronchodilator, and fairly typical increases with a bronchodilator in asthma patients. From our perspective, we were successful in demonstrating an acceleration of the FEV1 improvement by using IV administration, and that improvement was maintained through a 29-day follow-up in these patients. We had never treated a COPD patient with rademikibart. Although in the prior phase II-B asthma study, there were patients that had characteristics similar to COPD patients. We pulled those patients out, and we see that this data predicted a robust improvement in FEV1 in these COPD-like patients. As everybody I'm sure understands, COPD patients generally respond less well to these drugs. Improvements of less than 100 mL have been observed with most of the products developed for COPD, and we'll discuss that in a few slides. If we go to the next slide, which is the actual results from the COPD patients treated with IV rademikibart, you see here a very robust improvement in FEV1 occurring within 15-30 minutes. That improvement is generally maintained in that 300 mL-400 mL range, again, with a fair amount of variability. If one looks at the data from the dupilumab phase III studies, where they had 400-500 patients per arm, you see very substantial error bars. Spirometry itself is variable and among COPD patients, particularly highly variable. That's really the underlying reason for this bouncing around. Nonetheless, we see a really remarkable improvement in FEV1 in these patients. The speed of onset is so rapid we believe that this definitively identifies a second mechanism is occurring with rademikibart to improve airway function this quickly. We believe that some of the preclinical data that was previously reviewed is giving us at least an indicator of that differential pharmacology that's going on. How do we put the improvements of 300 mL-400 mL and greater into perspective for COPD patients? We can take a look at the older agents and what's a clinically important improvement with those. You see it ranges from, you know, 45 mL-50 mL to 100 mL-164 mL for combination treatment. With Dupixent, they have in their package insert, post-bronchodilator change from baseline placebo corrected at two weeks. We see about 10 mL-80 mL difference at two weeks, which compares to almost 400 mL increase with rademikibart at day 15 post-bronchodilator. Very substantial difference observed again in this small study. Ohtuvayre, very effective agent for COPD, produces peak improvement on day one of 152 mL-157 mL. That compares to almost 600 mL peak improvement at three hours with rademikibart IV administration, and the drug Ohtuvayre was actually approved based on AUC 0-12 change of FEV1. That was in the order of about 87 mL-94 mL in their two phase III trials, where AUC 0-12h for rademikibart is on the order of 400 mL on day one. To conclude the observations, we see extremely robust improvement in FEV1 around 200 mL-400 mL. This is very significant compared to both the old-line agents used in COPD patients as well as the newer products. As we've been identifying for some time, treatment of acute exacerbation, our current target, is a complete white space as the currently approved drugs, the biologics or Ohtuvayre, are all approved for chronic management and have explicit warnings in their package inserts to not be used to treat acute exacerbations or bronchospasm. There are no biologics or innovative products approved for acute exacerbations, and in fact, they are all prohibited from being used. This is an opportunity to have a completely differentiated indication, and we'll talk about the value of that in a minute. The next slide is the safety observations of which, as you can see, none to speak of in this small IV study. Just the highlights, you know, in addition to faster onset of airway improvement that we now have demonstrated with the IV administration. There's other additional benefits to us that accrue from using IV in the ER setting. First of all, it's a lower dose. Bioavailability of rademikibart from a sub-Q administration is about 50%, and so we can use a lower dose given IV, and we will likely evaluate an even lower dose going forward just to satisfy FDA requirements for appropriate dose evaluation. By having an IV product with a different indication dose presentation, so for example, a hospital use only vial for IV administered product, it gives us the opportunity to price differently in the hospital setting versus the outpatient auto-injector. We have here an example of that pricing difference. Ours wouldn't be nearly this large, but by being able to optimize the price in the hospital setting and in the outpatient setting results in the greatest commercial opportunity. Moving forward, we have two acute exacerbation studies ongoing, and the data from those will read out mid-year. Next slide is the design of those two studies. They're basically identical, aside from some modest differences because of the differences between asthma and COPD. Patients come in with an acute exacerbation. They receive standard of care, which is a steroid prednisone and a beta-agonist bronchodilator. Then they're randomized to receive rademikibart or placebo. We follow them for the endpoint for 28 days and then another four weeks just for a safety assessment. The goal here is to show a reduction in what we call treatment failure. This endpoint is patients coming back to the emergency room, back to the clinician, looking for additional medical treatment, for example, another round of prednisone, because they continue to get worse or they may get better briefly and then have another exacerbation during that four-week period. Now, when we were designing this study initially, we had found through the literature and through claims database that it looked like around 50% of patients, what I find is a shocking number, actually in the real world go back to the ER or to another point of care because they're continuing to get worse or they have another exacerbation in that four-week period. Then about that same time, next slide, the ABRA study was published. This is an investigator-initiated trial out of the U.K., contemporary data on what happens in patients, both asthma and COPD, having exacerbation. In their study, they found 45% of patients coming back to receive medical care during that four-week period. It gave us another piece of data in order to power the two phase II studies that we just reviewed. We've used this 45%, and we are looking for a 50% reduction, which, based on the benralizumab curve, certainly looks like a very doable outcome, considering the fact that benra had really no effect on the treatment failure for the first two weeks. It starts to separate after that. What that tells us is that benra is doing a very nice job of reducing new exacerbations, but had no real benefit for the index exacerbation, that acute setting in the first few weeks. With a product like ours that starts to work overnight, with significant benefit accruing to patients in terms of airway improvement, in that very short period, we anticipate seeing the active treatment curve much flatter than what's seen here with benralizumab. Again, top-line results from the two phase II studies anticipated mid-year. We've done extensive market research with the product, both clinicians and payers, et cetera. Very significant interest in using a biologic or any new tool to treat acute exacerbations. The data that we presented in these market research studies, I will tell you, was not as robust as the IV data that we just reviewed. We'll have to go back and do another round because the magnitude of the effect, particularly in COPD patients that we tested was nothing like what we're actually seeing in patients. Even with the less exciting data, we found a worldwide peak sales forecast of approximately $5 billion for acute and chronic indications in asthma and COPD. This just highlights the fact that there was significant interest in using rademikibart acutely in patients coming in with an exacerbation, and then significant interest in using the product chronically, particularly in COPD, which is a less crowded space, and where the recent approvals have not allowed enough time for dominant positions of any of the recently approved products. What was really the most profound was the preference share of 75% in both asthma and COPD, where clinicians told us if a patient received the drug acutely and did well, they would want to maintain that patient on the same drug to a very high proportion of clinicians. We see that the acute indication, number one, changes the perception of the drug in the mind of the clinician, and number two, is really a gateway to chronic administration, because the patient starts on the product acutely before they see another biologic, and then the clinicians have a very high preference to maintain the patient on the same drug. That concludes the new data in the respiratory area. I'll now move to the late-breaking data in atopic dermatitis. This is a study that was sponsored by our partners in China, Simcere Pharmaceutical, who has rights to develop rademikibart in Greater China for all indications. We receive significant milestones and tiered royalties for their development and ultimately commercialization activities. We'll go into the data. Next slide. The design of the RADIANT-AD atopic dermatitis study. Pretty classic design. 16-week blinded induction phase, and then patients are then put on long-term management out to 52 weeks. Baseline characteristics. Pretty classic for AD studies in terms of baseline disease. Here we get into the data. We found this data to really be quite impressive in terms of the response rates both at 16 weeks, but particularly at 52 weeks. This first slide is the classic endpoint of Investigator Global Assessment. Here you see 87.1% responders at 52 weeks. Next slide is EASI-75. Again, a pretty standard endpoint for these trials. We've never seen a 96.6% response rate. This is, we believe, about as good as you can get for this endpoint. To provide even greater benefit to patients, the next slide is EASI-90. A 90% improvement in the EASI score, which is Eczema Area and Severity Index. Again, very high response seen in this endpoint. Last but not least, pruritus improved substantially as well in this study. This was all done with very low side effects. You can see here the left panel is the blinded placebo-controlled, and the right is the longer-term follow-up. Probably the most important to highlight is the conjunctivitis, which is one of the most common side effects of dupilumab and many products in this category. You can see here that in the blinded placebo phase, the conjunctivitis rate was really not differentiated from placebo. While it goes up to a very small extent in the 52-week period, it's substantially lower than what's seen with other products. I'll give you an example of that in the next slide or two. The conclusions from this data, obviously rapid and sustained efficacy out to 52 weeks, with a very high proportion of patients obtaining near maximal response. Great long-term benefit in this study, with the 52-week data, and a very clean safety profile with low rates of conjunctivitis. If we go to the next slide, this is from our prior atopic dermatitis study. It just highlights two points. Number one is patients at 16 weeks in this study were re-randomized to either maintain Q2-week dosing or go to Q4-week dosing. You can see clearly there's no loss of benefit by moving to Q4-week. In fact, if anything it's slightly better in terms of the IGA endpoint. More important, this also highlights that with rademikibart you see excellent maintenance of responders. These are patients responding, whether it be IGA or an EASI-75. For example, on an EASI-75, you take the responders at 16 weeks, and you're looking to see how many continue to respond out at 52 weeks with almost 92% on Q4-week dosing. In the two dupilumab solo trials, only 54% of patients with the IGA endpoint maintained response from 16 weeks to 52 weeks. That's versus our 87%, substantially higher rate of patients maintaining that benefit over that period of time. As you saw from the graphics, that there's a continual improvement in the proportion of responders. We're gaining new responders, and we're not losing current responders. That's how we can get to that 90%+ response rate out at 52 weeks. Similar observations were made in the current AD study. That data and data from the adolescents will be presented at upcoming scientific meetings. The next slide, couldn't help myself. As you may be aware, a week ago, there was new information presented by Apogee on their long-acting agent in atopic dermatitis. They presented a lot of comparative slides, so I took the same tack and presented comparative data to what they observed at 52 weeks. This is looking at their Q3-month dosing, which was their best data. You can see at 52 weeks, we have 10%-15% higher response rates across the three key measurements, and a substantially lower rate of conjunctivitis. Just to put all of this information into perspective, in asthma and COPD, we have the difference in binding of rademikibart to the receptor results in enhanced internalization of that drug receptor complex, which then results in a clear difference in eosinophils observed with chronic administration, where we see a reduction versus an increase with dupilumab. We've also demonstrated a very unique mechanism of action, in terms of directly increasing phosphorylation of HSP 20, a marker of relaxation, in the cells and in bronchodilation in the whole lung. We've been able to reverse the negative effects of IL-4, IL-13 on the dose response curve of beta agonist in lung slice experiments, something that was not observed with dupilumab. We're in the process of testing other potentially competitive agents. The rapid onset that we see in subcutaneous administration of significant improvements overnight, we can successfully accelerate with IV dosing with substantial increases as early as 15 minutes, ideally suited for emergency department setting. We see larger increases in FEV1 than has previously been observed, and that's probably due to this ancillary pharmacology in addition to the IL-4 receptor alpha known pharmacology in terms of FEV1 improvements. Atopic dermatitis, very high rates of response for all of the key endpoints. We see very high proportion of patients going on maintaining efficacy through 52 weeks, compared to specifically to the dupilumab phase III studies. We see in a prior study excellent efficacy Q4 weeks. Q4-week dosing is something that we would go forward with in asthma and COPD patients as well. Based on the information so far from all of these trials, it appears that we have a substantially lower rate of conjunctivitis based on the data to date. Just to put everything into perspective, we also have very long exclusivity out into the early to mid-2040s, so plenty of time to benefit commercially. On the financial side next, we have cash equivalents, short-term investments at the end of the third quarter at last reporting period of $55 million plus the proceeds from the raise that we announced this morning. We have cash that's expected to cover operations into the second half of 2027. This is just a final summary of all the information that we've just reviewed. Most importantly, in terms of catalysts, most important catalyst coming forward is the completion and top-line results of the two phase II acute asthma and COPD studies, which we're anticipating midyear. There's also a pending New Drug Application in China for atopic dermatitis, which we're hopeful to see approved sometime between midyear and end of year. With that, thank you for your attention, and happy to take some questions. Thank you. As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Our first question comes from Thomas Smith with Leerink Partners. Your line is open. Hi, this is Nat Charoensook on for Thomas Smith. Congrats on the data. We have a couple questions. The first one, how do the IV results affect your strategy in future studies of rademikibart in acute asthma and COPD? Yeah, great question. This is very fresh off the press data from that study. There's still a few patients going on. We need to get the full data set and really delve into you know understanding the responders and making sure that we can you know move forward and identify the best patient population to respond. But we definitely are planning to switch to IV dosing ultimately moving into phase III for acute treatment with the IV. We'll be looking at whether there's a need to do any additional bridging work between this small IV study and moving forward early next year with the IV in phase III. Stay tuned. Once we have the full data set and analyze it, we'll make a decision on is there a need for additional work. Got it. Briefly on the economics from the Simcere partnership. Connect remains eligible for about $110 million for milestone plus tier royalties. Which milestones are the nearest term, and what an approval would unlock? A great question. We have not divulged the specific individual milestones. You are exactly right that there's still $110 million in milestones that is due to Connect from our partners, Simcere, based on both development, regulatory, and commercial endpoints. You know, we haven't given the explicit numbers, but milestone for the first approval, which in this case we would anticipate being AD. And then, Simcere is also currently conducting a large chronic asthma study. Early next year, we would hope to see excellent results from that study, and we'd anticipate that they would be filing for approval in asthma sometime later than that, and we would receive another significant milestone for an approval in asthma as well. Got it. Thanks again, and congrats on the data. Thank you. Thank you. The next question will come from Brandon Folkes with H.C. Wainwright. Your line is open. Hi. Thanks for taking my questions, and congrats on the data. Thank you. Maybe just two from me. In Part B of the IV study, any color or insight into the number of subjects which returned to the ER within 29 days? You know, granted these were stable patients, but I think it would just be interesting to sort of see if there's any data there ahead of Seabreeze. Yeah, excellent question. We will have to delve into that once the last patient is completed and definitely something that we'll be looking at. I'm currently unaware of any exacerbation in this small cohort of patients over the 28 days, but there may be something interesting in there. We'll certainly make that known if we find something interesting. Okay. Thanks so much. Secondly, so on the asthma cohort, yeah, why do you think FEV1 comes down until 90 minutes? Yeah, is that just given sort of the law of small numbers here? How does that potentially compare to the sub-Q? Do you have any data there? Then, I guess, yeah, going forward, would you expect similar curves to what we saw today between COPD or asthma? Or would you expect asthma to sort of look a little bit like or a lot more like COPD going forward? Then on that, you know, if we do see the asthma curve like today, does that bring in any risk of symptoms or exacerbations between minute 15 and 90 in sick patients? Thank you. Thanks, Brandon. Good question. You know, we believe based on looking at the individual patients that this is just inherent variability of spirometry. In that early period, as you note, I mean, we are collecting a very sizable number of tests over a short period of time. You know, there's always a possibility of patients, you know, asking them to do a baseline, and they may do, you know, six, seven attempts, and then, you know, 15 minutes later, another, you know, six, seven attempts, and 15 minutes after that, at 30 minutes. Among all of those assessments, there's a substantial amount of variability. We don't see that as a real observation in terms of something happening with the drug effect. I think the COPD patients, for whatever reason, were more stable actually in general than the asthma patients. In both settings, we're talking about very small numbers. This was a small, you know, clinical pharmacology study. I don't think we wanna read too much into an individual data point. No, we expect in larger scale studies to see, you know, more consistent results early on. Even if it did bounce around, it certainly should not have an impact on patients who are having an acute exacerbation. They're already there, having an acute exacerbation. They're already on, you know, the standard of care in that very acute setting. Certainly not gonna have a negative impact on those patients. Great. Thanks very much for taking my questions, and congrats again on the data. Thank you. Good to talk with you. Thank you. The next question will come from Thomas Flaten with Lake Street Capital Markets. Your line is open. Hey, good morning. Thanks for taking my questions. Barry, just to follow up on that last response. I mean, what stood out to me with those two charts in asthma and COPD was the rapid or more rapid response into the marked bronchodilator response zone, the green zone in COPD versus asthma. I'm just assuming the answer is the same as you gave the last question, that it's inherent variability in small number of patients, et cetera, but that's the one thing that stood out to me. Just curious to get your thoughts on that. Yeah. Well, it's an excellent observation. There's no question that the response in the COPD patients was much more robust than in the asthma patients in that first several hours, and actually even beyond that. It's very intriguing because we are still trying to understand the reasons why we see such rapid improvement in FEV1. Clearly, it is not a direct IL-4 effect because at least in cell culture and in lung slice, we don't see this, these kinds of effects with dupilumab. There's that ancillary pharmacology that we're really still trying to get our hands around. Ultimately, I won't be surprised if that pharmacology has potentially greater impact on COPD, because I'll point out that, you know, we had looked at these COPD-like patients and found really remarkable increases in FEV1 in that subset of patients. It was actually kinda too good to be true given how resistant COPD patients tend to be. Remarkably, we actually duplicated almost exactly that same magnitude in this small study. I feel that it is real. It's a real observation. We're gonna spend some time drilling into it to figure out what's the underlying biology. Just a kind of a 50,000 ft question. You know, you've got the Seabreeze studies ongoing, so acute exacerbation seem to be the number one priority. How are you thinking about allocating resources across chronic asthma, COPD, and AD, given this excellent data set that was presented over the weekend? Yeah. Thank you. Appreciate the question. Number one, we've been pretty clear that we are personally, the Connect company is not going to be expanding resources on atopic dermatitis, you know, at this juncture. We think that the drug has an opportunity to be best in class in atopic dermatitis, but it is not our current focus. We'll continue to focus on the respiratory side. In terms of you know, how we'll move forward, as I previously noted, our intent is to be in both acute and chronic. We've put the chronic studies on pause while we generated the acute data. Once we have the acute data, we already have agreement with FDA on moving forward in chronic asthma into phase III based on the great phase II data we generated. You know, early next year, we would certainly look to initiating both acute and chronic phase III studies. At that same juncture, we'll be likely getting the results from the Simcere phase III asthma study. The great thing is that virtually everybody in the world uses GINA guidelines for treating asthma. That study from China, we believe should be acceptable for submission to FDA and acceptable as at least a you know supportive phase III trial. Based on the results of that, we'll certainly plan to move forward into you know both acute and chronic. You know, as we've also maintained, our interest is, you know, finding a commercial partner for rest of the world, to help defray the costs of certainly, you know, not interested in going out and raising, you know, phase III dollars for multiple acute studies, and, you know, phase III in chronic and chronic asthma and chronic COPD. The goal is to be able to move forward early next year, but to have somebody help pay for it. Great. Appreciate that, Barry. Thank you. Thank you. The next question is gonna come from Julian Harrison with BTIG. Your line is open. Hi. Thank you for taking the questions, and congratulations on these results. Thank you. In your IV study, the FEV improvements, especially in COPD, looked very high, like multiples higher compared to other treatment options. I understand there maybe was an expectation for faster efficacy with the IV formulation, maybe Tmax driven, but I was wondering if you were expecting such a large treatment effect from this early study, and if so, you know, maybe any thoughts on what was driving that? Yeah. Thank you for the question. You know, we had the data from the prior phase II-B chronic study, where we pulled out the COPD-like patients and showed, you know, particularly in people with T2-mediated disease, 400 mL- 500+ mL improvement, which I will say, I thought was, you know, a wonderful observation but highly unlikely that we would be able to replicate, because COPD patients tend to be much more resistant to pharmacologic intervention. There's more remodeling, and other factors involved in their airway dysfunction. Seeing almost identical results in this small IV study certainly gives me greater expectation that we will in fact continue to see that kind of magnitude going forward. We obviously won't know for sure until we do larger experiments, but being able to replicate that almost exactly certainly would indicate to me that that is in fact a real observation and not just the, you know, an artifact of very small numbers. And as in terms of your second question, we have every interest in trying to figure out exactly the underlying pharmacology. We haven't got there yet. We have tantalizing pieces of information that I showed you, but we have a lot of work ongoing, and we feel we will figure that out, and I look forward to being able to present that in the future. Excellent. Thank you. A follow-up, if I may. It was also interesting to see the data showing rademikibart potentiates beta agonists. I understand that was also maybe an unexpected effect, but just wondering if there was a prevailing explanation there, or is that kinda just left as an empiric observation for now? Well, we, you know, we know it's real. We know we're differentiated from at least dupilumab in that regard, and I expect probably from every other biologic that's used for asthma and COPD. It is clearly an off-target effect of the drug. We don't know if it's associated with this internalization or some other factor, and that's really our significant focus in terms of the preclinical area of understanding exactly how it is doing that. We know it's doing it. We understand from the HSP20 data that it's doing it downstream. We know that the cytokines block beta-agonist activity upstream. So, that all fits together, but the exact molecular basis for doing it is still unclear. As I said, looking forward to presenting that in the future. I think we're out of time, so I thank everybody for joining the call today. This does conclude today's conference call. Thank you for your participation, and you may now disconnect.