Good day, ladies and gentlemen. Thank you for standing by. Welcome to the Connect Biopharma Conference Call. At this time, all participants are in 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. Please be advised that today's conference may be recorded. I would now like to hand the conference over to your first speaker, David Szekeres, President of Connect Biopharma. Please go ahead, sir. 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 the top-line results we're announcing today, the timing and content of additional data analysis and future data presentations, our anticipated regulatory strategy, interactions with the FDA and other health authorities, the design, initiation, timing, and results of future clinical trials, our cash runway, and anticipated use of capital, and our future expectations, plans, prospects, corporate strategy, and performance. Actual results may differ materially from those indicated by these forward-looking statements due to various important factors, including those discussed in the Safe Harbor slide, the press release 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. Thank you for joining us this morning. We are very pleased to have this opportunity to review with you the results of the Seabreeze STAT asthma study. Overall, we achieved our objectives to demonstrate that rademikibart works quickly to improve airway function, and that this improvement results in substantially fewer patients returning to the hospital, emergency department, or clinic for additional care in the months following the asthma attack. Unfortunately, the overall rate of treatment failure in the study was substantially lower than projected. Even with a larger effect size than projected, we still just missed statistical significance. Where the study did achieve statistical significance is in the equally important and more challenging key secondary endpoint of FEV1 improvement on day seven. We see this endpoint as more challenging because patients are recovering from an acute exacerbation, a population almost never included in clinical trials, and they are receiving aggressive treatment for their acute exacerbation, including systemic steroids and bronchodilators, which result in a sizable increase in the placebo group. We are then asking rademikibart to improve airway function even further, and it does exactly that. The increase in FEV1 at day seven with rademikibart is more than twice what is obtained with bronchodilators alone. I will also note that benralizumab, which showed significant reduction in treatment failure in the ABRA study, showed no benefit in FEV1 or other measures of respiratory function through 28 days. Improvement in FEV1 has also been used as a primary endpoint for the approval of Ohtuvayre in COPD. It is an established regulatory endpoint. We believe that demonstration of rapid, significant benefit in FEV1 provides a clear roadmap to phase III, which we intend to confirm with the FDA later this year. Lastly, rademikibart continues to be remarkably well-tolerated. I will not spend a lot of time on the design slide, but I will note that we use the same entry criteria for previous exacerbations in the prior year as the ABRA study. Here is the schematic of patient flow. We screened 323 patients in order to enroll 160 patients. Here is the breakdown of baseline characteristics. Of note, enrollment into the study went quickly in Eastern Europe, resulting in a high proportion of patients coming from Serbia and Georgia. Although these countries, and more specifically the hospitals we used, follow the same treatment guidelines as we do in the U.S., there may be other aspects of patient care that impacted the unexpectedly low rate of treatment failures observed in the study. Here are the results for the primary endpoint. You may recall that Study 206 was powered based on a 45% placebo treatment failure rate, with approximately a 50% reduction observed for benralizumab in the ABRA study at 28 days. While the 66% reduction seen with rademikibart exceeded the target 50% reduction, there was just not sufficient events to reach statistical significance. In this study, the majority of events resulted in an unscheduled visit to the clinic or emergency department. Fortunately, no deaths or hospitalizations. Within patients experiencing a treatment failure, there were five exacerbations in the placebo group compared to two in the active arm for a 60% reduction. Slide eight clearly shows why treatment failure is not a useful endpoint for demonstrating an acute pharmacologic effect. Within the first week where we demonstrate a significant improvement in FEV1, which you will see on the next slide, there are no treatment failures, probably because patients are covered by steroids for most or all of that week. Conversely, on slide nine, we see that the airway improvement with rademikibart starts quickly and is almost at stat sig by day three. By day seven, the benefit of a single dose of rademikibart has been fully achieved, and we see a plateau in FEV1 through day 28, providing additional support, I might add, for monthly dosing. The beneficial effects of a single dose start to wane by eight weeks, which we see as an ideal scenario for an acute-to-chronic development strategy. The next two slides cover safety, which were entirely unremarkable, with fewer AEs and SAEs on drug than placebo. No episodes of hypereosinophilia were noted in the study. Slide 11 just breaks out the individual SAEs, adverse events of special interest, and treatment-emergent adverse events. Conclusions. Clinically meaningful 66% reduction in treatment failure observed through day 28. Rapid, statistically significant, and clinically meaningful increase in post-bronchodilator FEV1 compared to placebo observed at day seven and maintained through day 28. Day seven FEV1 improvement was a pre-specified key secondary endpoint based on the FDA's desire to have an endpoint showing rapid benefit for a potential acute indication. As noted, we plan to propose FEV1 improvement at day seven to FDA as a phase III endpoint for the acute indication. Based on our prior phase II-B 24-week study showing a 63% decrease in annualized exacerbations in the T2 population, and this study showing substantial benefit in exacerbations as well, we are perfectly situated to also move forward with a chronic maintenance program in asthma. Based on the very low rate of treatment failures in this study, it is reasonable to ask whether there is really a market for treatment of acute exacerbations. Our prior market research was somewhat dated, so we engaged Komodo Health to generate a much more contemporary picture of the market as it was in 2025 based on actual claims. The results are remarkably positive for a product with rademikibart's profile. With approximately 1.6 million emergency department visits in the U.S. for acute asthma attacks in T2 high patients in 2025. There is essentially zero biologic penetration into this acute market, and there is still very low penetration into the chronic market as well, with a very low 2.26% of all asthma patients that received an asthma biologic in 2025, rising to 3.44% among the type 2 high subset, leaving a very large untapped market. Slide 14 is just a snapshot of the massive Komodo Health database, and slide 15 is the money slide. Approximately 1.6 million ED visits in 2025 with T2 high asthma patients flowing into three buckets. The largest is treat and release. These are patients who come in, treated in the ED, and then released. There's an intermediate group in the middle where patients can be observed to see if they are improving and then discharged or worsening and then admitted. Finally, the patients going directly to a hospital bed from the ED under the admitted bucket. The slides provide the percentage of each bucket who return within 30 days based on actual claims data and the associated costs. From that, we can calculate the total cost for patients returning to the ED or the hospital and how much theoretically can be saved by reducing returns by 66%. Based on this model, giving patients in the middle and right buckets a drug that produces a reduction that we've observed would be highly cost-effective, and certainly a large portion of the treat-and-release patients would also be very cost-effective. With that, we are happy to entertain any questions you have. Operator? Thank you. Ladies and gentlemen, if you have a question at this time, please press star one one on your touch-tone telephone and wait for your name to be announced. To withdraw your question, simply press star one one again. Please stand by while we compile the Q&A roster. Our first question coming from the line of Biren Amin with Piper Sandler. Your line is now open. Yeah. Hi, guys. Thanks for taking my questions. I've got a couple. In April, the DMC conducted an NROM on treatment failure at 28 days for the trial and recommended no change in sample size after the first 50 patients were enrolled. Given that's about 1/3 of all patients enrolled in this study, wouldn't the DMC have picked up on the lack of exacerbation events and recommended an increase in sample size? Yeah, great question. Going back and looking at the sequence of events, what we actually find is that the first group of patients with treatment failures were all in the control group. So what they would've seen is a, well, low number, a very slanted towards placebo group of treatment failures. From the perspective of going to the full study, that would've resulted in potentially 10-ish patients on placebo, zero on drug, which certainly would've hit statistical significance. The other factor was that that was not a futility analysis. We gave them specific instructions that if there was a benefit to increasing the sample size by 10% 20%, or 30%, that they should identify that. If not, then the feedback should be no change. The feedback was, in fact, no change, which I think was not an unreasonable response from them based on the data that they had to look at. Got it. My second question on FEV1. Clearly, you are seeing a statistically significant effect on post-bronchodilator FEV1. FDA also, I think, looks at FEV1 trough. Have you measured FEV1 trough, and what do the data show versus placebo? Well, that is the challenging part of this type of study is that you are enrolling patients coming in for an acute exacerbation. As soon as they walk into the ED, the first thing they are going to get is extensive bronchodilator therapy. It is virtually impossible in those patients to get a pre-bronchodilator or what you call trough FEV1. While you may remember the prior WW002 study where we presented data on FEV1, all of that data was pre-bronchodilator. You get a trough, you give the drug, and you are looking for a benefit. It is actually much easier to see a benefit when using that approach. In this case, we did not really have that option because patients are already on bronchodilator therapy. You cannot withhold it. That would be inappropriate in this setting. We had to look at post-bronchodilator benefits of the drug. You are giving max dose bronchodilator, and then on top of that, you are giving either placebo or drug, and you are trying to see an additional benefit. That is what we are showing here. Unfortunately, we do not have the luxury of looking at a change from pre-bronchodilator effects in these patients. Great. Thanks for taking my questions. Thank you. Our next question in queue coming from the line of Julian Harrison with BTIG. Your line is now open. Hi. Thank you for taking the questions and appreciate the update here. I have a few questions, and I think I'll just ask them all at once. First, can you talk about the extent of your alignment regarding the 7-day FEV1 endpoint being accepted by the FDA as a registrational endpoint in phase III? Are there maybe any composite endpoint contingencies that you're also planning for? Second, I'm curious about any comments you could share with regards to the baseline exacerbation rate in the COPD study, and what could that maybe mean for the primary endpoint in the COPD Seabreeze STAT study. Then finally, I'm wondering if it's decided at this point whether you will be advancing an IV or subcutaneous formulation into phase III. Can you maybe walk us through your updated thought process there? Yeah, certainly. Thank you. Great questions. I think we were very clear after meeting with FDA and moving forward with the program that we had a great discussion with the division. They totally appreciated that this was a clear unmet need, that this is a population of patients virtually almost always excluded from clinical trials with no new drugs or drug development in over 30 years. Because of that, they also were quite candid that they have never approved a drug for acute treatment. They could not give us, at that meeting, explicit guidance on, "Here's the endpoint. This is what we expect to see," et cetera. We moved forward with the study as designed because the treatment failure endpoint seemed quite attainable based on the ABRA study. It gave us contemporary expected rates of events where, in terms of FEV1, there's virtually no information in the literature on what to expect in a patient coming in with an acute exacerbation. How much change can you see? What would we expect to see in the control group, et cetera? It was an opportunity to obtain all of that information in the current study. We do know the agency was very clear that they are looking for an acute benefit for an acute indication. That benefit seen out at three, four weeks wouldn't be considered an appropriate endpoint for an acute indication. We've always, as noted, we elevated based on our discussions, the FEV1 at one week to a key secondary endpoint. We've always been focused on demonstrating benefit in both the treatment failure as well as the key secondary endpoint of FEV1 improvement. We anticipate the agency to certainly be positively inclined in terms of accepting this otherwise regulatory validated endpoint. Whether or not day seven is going to be the target for them, that's something that we'll determine when we meet with them. But we anticipate a certainly positive overall response. In terms of the COPD study, we are seeing more events in COPD and, probably equally valuable, more of those events are resulting in hospitalizations and emergency department visits. I think we will have the opportunity, hopefully, to see statistically significant as well as be able to really demonstrate the clinical benefit of reducing that endpoint. As well as obviously we'll be looking at FEV1 in those patients. Although again, that's a very challenging group because many of them don't respond to beta-agonists at all. It should be a very informative data set. In terms of your last question, we are currently doing a bridging study to obtain more data on use of IV rademikibart in the setting of an acute exacerbation. We intend to have that data fairly quickly, a small study, and then be able to discuss that with the FDA when we meet with them at the end of the year. Certainly, we believe that the IV dose has the opportunity of much faster onset, even faster obviously than the sub-Q administration. It has a really ideal profile for use in the emergency department. But we're also looking at the option of potentially developing both IV and sub-Q for the acute population now seeing the magnitude of the opportunity. We know that IV is not really suitable for urgent care. It's not really suitable for most clinics. You'd like to have a label that gives the optionality of using the IV or potentially using the sub-Q administration in a setting outside of the ED. More to come on that. Very helpful. Thank you. Thank you. Thank you. Our next question in queue coming from the line of Olivia Saunders with Cantor Fitzgerald. Your line is now open. Hi. Good morning. Thank you for the questions. Barry, what's your expectation just around the risk that COPD may also be underpowered because of low event rates, just given the similar treatment failure assumptions and the endpoint definition? Is there any reason to think that we could be looking at a different outcome on the primary in a couple of weeks? How does the low proportion of U.S. patients in phase II actually read through to potentially enrolling patients in a pivotal study? I'd assume you would need a higher proportion and number of patients in the U.S. for the pivotal, but appreciate any thoughts you may have here. Yeah, no. Excellent question. I cannot obviously give you any other color on COPD other than there are more events. Certainly there is the risk that we will end up potentially not hitting statistically significant, but my guess is we either will hit it or it will be much closer than we are in the 206 study. Unfortunately, I cannot give you assurances. The overall rate certainly is still not up to the ABRA study event rate. In terms of the enrollment, I think we have learned a great deal, and we will continue to drill into the data that we have obtained from patients and look at both individual study sites as well as countries and get a better sense for where we would want to go back for phase III. It may mean that we avoid certain locations based on looking at both the event rate in terms of treatment failure, which, as noted, will not be a primary endpoint. But we will also be looking at the benefit in terms of FEV1 and other issues across the different regions. We did find that while delayed in starting, Argentina looks like an excellent location as well to enroll patients. But certainly, we will continue to look for the ability to enroll more patients in the U.S. I think the key is going to be not only trying to enroll more people in the U.S., but making sure that we are going to regions where we see very comparable results in terms of what we see in the U.S. and that the medical care is as closely aligned as possible. We do not always have phase III studies that are majority patients in the U.S. You just have to make sure that those patients are as close as possible to what you would see in U.S. healthcare. But we will certainly be working hard to try to open up more sites and get more patients in the U.S. population. Okay, great. Helpful. Thank you. Thank you. Our next question coming from the line of Thomas Smith with Leerink Partners. Your line is now open. Hey, guys. Good morning. Thanks. Thanks for taking our questions. Just with respect to the path forward in asthma, assuming you gain alignment here with FDA on FEV1 at day seven as a primary endpoint, any early thoughts on study size and how long it might take to run that program? Thinking about the COPD study, just talk a little bit about how much overlap there is in the study sites between the asthma and COPD studies. Is the balance of enrollment coming from basically the same regions in COPD as it was from asthma, this predominantly Eastern European population? Thanks so much. Sure. The last question, there's a great deal of overlap in the overall basic proportions of patients. I think are very similar. Majority of patients are coming from Serbia and Georgia. As noted, while we are seeing more events, we're still definitely not seeing the level of events up to the original projected 45% treatment failure from the ABRA study. I apologize, I've forgotten your first question. Yeah, just in terms of the asthma phase III plans, assuming you are able to gain alignment with FDA on FEV1 at day seven as a primary. It just helps us think about how large that study would need to be and I guess any early thoughts on how long it would take to run that program. Yeah. Thank you. This data is really hot off the press. Pushing hard to get it together for this release. We really have not had the opportunity to sit down and do the appropriate calculations. Just off the top of my head, I will say that we would certainly be looking at a larger study in order to make sure that we had the usual highly powered phase III study. I do not think it would be anything more than twice the size potentially, but we really have not done that calculation yet, and we really need to understand the data a little more and drill into it. Certainly it would be a larger study, but not 5x. We will obviously have that discussion with FDA. In terms of timing, I think we learned a great deal from the phase II study, doing a trial that really few, if any, sponsors have ever done. We have a much better sense of how to get these patients enrolled and certainly where to go and where to not go. I will turn it over to Kimberly to give an assessment of the timeline for conducting such a study. Thank you, Barry. Yes, as mentioned, we plan to meet with the FDA later this year, and then we anticipate being able to start within about three-four months, if all goes well. The phase III program, it will go in stages depending on the countries that we are selecting. Obviously the size dictates how long the study will be to enroll. Fortunately, these are short studies to conduct after you do enroll, but we anticipate we could have data within approximately 1.5-2 years, again, depending on when we are able to start. Got it. That's super helpful. Maybe just one follow-up, if I could. Are you able to provide any additional updates on the status of rademikibart in China and some of the progress your partner's been making there? Thanks so much. Sure. Well, I think probably from a certainly development perspective, we're eagerly awaiting the conclusion of their phase III asthma study, which should conclude in the first quarter. All of those patients were fully enrolled late last year, so it's just a question of waiting the 52 weeks for the last patient to finish. We're very eager to see that results and certainly plan to use that as a supportive trial, obviously with a positive outcome of a supportive phase III study, reducing the amount of work that we have to do separately. On the approval front for atopic dermatitis, they were very anxious to get the new phase III study results into their package insert, so that they could launch with the best possible data. Unfortunately, in China, there isn't a mechanism to submit new data while an application is being reviewed, so they had to officially withdraw it and then resubmit it earlier this year, which then reset the clock. Initially, we had the expectation that since the government health authority had already gone through virtually all of the package and had already inspected sites, that this kind of resubmission would go more quickly. At this point, it looks like it's going to take the full normal duration. We'd probably be looking at an approval in the first quarter to April timeframe next year. They can submit asthma even before they do get approval for atopic dermatitis, depending on the sequencing. Got it. That's helpful. Thanks so much. Thank you. Our next question coming from the line of Edward Nash with Canaccord. Your line is now open. Hi. Good morning. Thanks for taking my call. Just wanted to know if, since obviously you'll have both the Seabreeze STAT COPD and asthma in hand when you go to meet with the agency, if the Seabreeze STAT COPD trial meets the primary on acute exacerbations, would this change at all your planned path forward? I know it's a much more difficult patient population to treat, but just curious if that would all would change kind of your direction of which of those indications you'd put first. No. Obviously, we would be very pleased to have statistical significance in treatment failure. But it would definitely not change our view of what's the appropriate endpoint for acute indication. I'm very confident it wouldn't change the FDA's view. Again, they were quite clear that they want to see an acute benefit. They couldn't give us guidance on exactly what endpoint and the magnitude that they want to see, but they were clear it had to be an acute benefit, not a benefit that they see as a typical chronic maintenance endpoint. As shown in the treatment failure Kaplan-Meier, and pretty similar to what was seen in the ABRA study, there are not a lot of events in that first week or two. Even if we ultimately do see statistical significance, even if we had statistically significant in this study, we wouldn't be going there with a treatment failure endpoint for phase III acute. It just doesn't fit with the desire to see a rapid onset of effect. Got it. Based on the FDA wanting to see an acute effect, but not necessarily specifying what that endpoint would be. We've obviously been talking to K Wells, as I'm sure you guys, your intel with doctors. What's been, I guess, top of mind for them on really being able to be competitive in the market? Is having an effect on, or a faster effect on FEV1 just as important as saying have an effect on acute exacerbations, which is a tool they currently don't have? Yeah. I think that the thing that resonates with clinicians is speed of onset of effect, which is very different than what the tools they have available. Something that has been evaluated in an acute setting. Recall that all of the biologics approved for asthma and COPD all have precautions not to use in a patient having an acute episode, not to be used for bronchospasm. Number one, you want a differentiated product that's demonstrated a benefit in that setting. The benefit that resonated in the original and subsequent market research was rapid improvement in airway function. It was the number one item that we identified as the benefit of the product, and that's what clinicians found most attractive. Now, of course, they also want to see that flow through to fewer people coming back to see them. That's certainly what we saw in this study, and what we hope obviously to see in the COPD setting as well. We do see a robust reduction in treatment failure, that, in this case, is well-correlated to the improvement in airway function. Having certainly a significant improvement in airway function and at least a strong trend in terms of reducing patients returning to the ER is what's going to resonate the most. Got it. Thanks very much. Sure. Thank you. Thank you. As a reminder, to ask a question, please press star one one on your touchtone telephone. Our next question in the queue coming from the line of Mazahir Alimohamed from Oppenheimer. Your line is now open. Hi. Thanks for taking our question. This is Michael Ong from AV. Just one quick question from us. Was there any difference in the duration of systemic steroid therapy across different study regions, particularly between Eastern European and U.S. sites, that might explain the low placebo event rate? Given that COPD exacerbation patients generally have worse baseline lung function and higher readmission rates, would you expect that the disease profile to naturally produce a higher control arm event rate in the Seabreeze STAT COPD study? Thank you. Yeah. That's a really excellent question and one that we have definitely not had time to evaluate in terms of background therapy. Everybody was mandated to get a relatively high course of prednisone. However, we also can't impact on what the clinician believes is medically necessary. We do know that there were some clinicians that tended to use longer duration prednisone, out to 10 days in some patients that they felt required that longer treatment. You're absolutely correct. We will definitely be looking at that to see whether there were any clear differences by region or hospital in terms of that background therapy, and trying to understand the potential impact of that. One thing we have noted is that while we used the same entry criteria for patients' previous exacerbations in the last 12 months before enrollment. You can see from the baseline demographics, we ended up with an average of about 1.6 exacerbations in the prior year, equally distributed between the two arms. But in the ABRA study, for example, it was more like four- five prior episodes. That really does identify a very unique, very high exacerbating group. So that also may have been why they saw such a high rate in the ABRA study. I think that from the Komodo data, we now see that the expected rate in a typical real-world setting is more like 17%-20%. Certainly that's a more realistic target. We didn't quite reach that either in 206, and exactly as you mentioned, we will certainly be drilling into the data to try to understand better how to potentially modify that. But to be honest, in the end, we don't see treatment failure as the appropriate phase III endpoint for acute and for chronic. Obviously, annualized exacerbation rate is pretty much standard. We already have a good picture on our ability to improve that, both from the prior phase II study, and definitely in terms of the first month of treatment from the current study. Great. Thank you. Thank you. Our next question coming from the line of Thomas Flaten with Lake Street Capital Markets. Your line is now open. Hey, good morning, Barry. Thanks for taking the questions. I know we've kind of beaten this one to death, but with respect to the enrollment rates differing so drastically between Eastern Europe and the U.S., was there anything else? Were there timing differences? Were there competing studies? Was there anything else you could point to in terms of things you might have a handle on? Well, I think that those sites started around the same time or actually a little after some of the U.S. sites. It wasn't that they got a jump on the U.S. participation. It's just that they started very, once they got through regulatory approval, et cetera, they started enrolling very quickly. We see that as based on a couple factors. Number one is the lack of availability of biologics. This is an enticing opportunity. Then the way that their medical system is set up with massively large hospitals, everybody is all in the same place. Patients come back to that location for all medical care. The pulmonologist's office is down from the emergency department, so they had a much easier time identifying those patients and getting them into the study. We continue to work with U.S. investigators, trying to optimize the trial design and make sure that we can get as much participation in the U.S. as possible. We just don't have exactly that same kind of setup, where you have easy access of a pulmonologist PI to patients coming into the ER. It usually takes a little time for that patient to be identified, and then at that point, the question is, how long can you wait before the event is kind of already waning and you're not going to be able to show as much benefit as you would in the real world where the patient's going to get the drug in the ER. And so that's really part of the dilemma is can we speed up that process. We're certainly experimenting with ways to do that in the current bridging trial, Study 209, that we have ongoing. We're pushing for a much faster turnaround of these patients, and we're using that to learn what we can do to improve enrollment activities. Got it. I know I'm jumping ahead a couple steps here, but could you just map out for us what a potential phase III would look like if you want to do sub-Q and IV? Would you consider having both of those in the same study, or would there be some other mechanism for getting the label broadened to include both routes of administration? It certainly would highly unlikely be in the same study. We generally think about doing two phase III studies, although FDA has indicated that one phase III might be acceptable. One could certainly look at a potential discussion with the agency around doing one IV study and one sub-Q study in order to get the broadest label, allowing patients to get acute treatment in an outpatient setting as well as in the ED. So basically using the studies together to demonstrate acute benefit, just different routes of administration. Got it. Appreciate that. Thank you. Thank you. I am showing no further questions in the Q&A queue at this time. I will now turn the call back over to Mr. Barry Quart for any closing comments. Thank you, operator, and thanks to everyone for joining the call today. We look forward to keeping you updated in the future. Thank you very much. This concludes today's conference call. Thank you for your participation, and you may now disconnect.