Good afternoon, everyone. My name is Anqi Yu. I'm a team member of the Biotech Research Team here at Jefferies. Today, we're happy to have Astria and Jill with us to give us a first chat about Astria. Welcome, Jill. Thank you. Glad to be here. All right. For those who are not quite familiar, could you please give us an overview for Astria? Absolutely. At Astria, we are focused on bringing first-choice products to people living with allergic and immunologic diseases. What we mean by first choice is that patients and physicians will choose our products first because of their competitive efficacy, good safety tolerability profile, and importantly, very low treatment burden. Our lead program at Astria is navenibart, which is a monoclonal antibody inhibitor of an enzyme called plasma kallikrein. Plasma kallikrein is a clinically and commercially validated target for the preventative treatment of hereditary angioedema, and we're currently in phase III with navenibart. What excites us about navenibart is the efficacy profile that we've produced to date in our proof-of-concept trial in patients, which showed a greater than 90% attack rate reduction in patients when dosed once or twice during six months. That profile, that data supports our potential for dosing navenibart as infrequently as every six months. That's what we've taken forward into our phase III clinical trial, both a Q3-month dosing regimen and a Q6-month. We also have a second program in the pipeline, as you know, STAR-0310, which is a monoclonal antibody antagonist of the OX40 receptor, a mechanism that's important in T cell biology. We expect to have phase I healthy volunteer data later this year. Fantastic. Maybe for the moment, let's focus on HAE. This is a very active space. From the clinical learnings, you have shown more than 90% of attack rate reduction, and also attack free rate is pretty compelling. Can you share with us so far, what do you hear from physician communities? How do they evaluate across two different efficacy endpoints? How to define best-in-class, given there are so many competing programs in this space? Yeah, great questions. From an efficacy endpoint, certainly what physicians look at as they look at programs, of course, is the endpoint that is used in all pivotal phase III studies, so time normalized attack rate reduction compared to placebo. That is really what physicians we believe will be looking at as they think about navenibart versus other programs. Of course, there are other factors that come into play as well. Certainly, attack free is very important, and that is something that we are monitoring and is a key secondary endpoint in our pivotal phase III, because, of course, patients want to remain attack free. We believe navenibart has a good chance of producing a highly competitive attack free rate in this phase III as well. Fantastic. Also, the data update from the long-term open-label trial in HAE of ALPHA-SOLAR is expected in mid of this year. Could you share with us how should we set expectations and what kind of read-through to the future pivotal trial readout? Yeah, ALPHA-SOLAR is the long-term extension trial from our phase I-B trial. All of the patients from our phase I-B/II trial chose to enroll into ALPHA-SOLAR, so we took that as a good sign. What we expect to show is long-term safety and efficacy data. We would expect to see similar to what we saw in that phase I-B/II trial in terms of attack rate reduction and the safety tolerability profile. We're on track to share that data mid this year, coming up. Would you be able to help us to narrow down how to define mid year of this year? Because we are already in June. Yes, so certainly we're in June, and that's right around mid year. We haven't disclosed publicly where we'll be releasing it, but yes, we are on track for mid year. Okay, fantastic. You asked about read-through to the phase III. Of course, we expect the data will be in line with what we've seen in the phase I-B/II trial for navenibart. The design of our phase III, of course, was designed from the results that we've achieved to date. We would expect our premise has been for navenibart that we believe we could support an 80%-90% attack rate reduction in that pivotal phase III. We'll certainly be looking to see what we see on attack free. Do we expect the same difference from three months versus a six months cohort? We don't. We have designed the doses going into our pivotal phase III based on the data we have generated to date. We believe the efficacy range for both cohorts will be in that 80%-90% attack rate reduction range. Does this data have some implication in terms of the timing of regulatory filing post the phase III readout, in another way, like shed light on the follow-up time of pivotal trial? Are you asking about the ALPHA-SOLAR extension? Yes. The ALPHA-SOLAR, that data certainly will be part of the package that ultimately goes with our filing to the FDA and other regulatory authorities, but the ALPHA-SOLAR data is not critical path to that. Great. Thanks for clarification. Also, talking about HAE market opportunity, would you be able to help us to put a number on that? How does this market evolve for this couple of years? Yeah, so the HAE market is large as far as rare diseases go, and it's been growing. We expect the market to grow to about $5.4 billion by 2030. We expect that growth to be largely driven by patients being diagnosed earlier, geographic expansion of drugs, as well as more patients going on to prophylactic therapy. When we get into how the market is shaping up in terms of across the different therapeutics, I think there are oral therapeutics, there are the long-acting injectables like navenibart, and the other injectables. I think navenibart and the profile that we believe we can support in this phase III has the potential to allow navenibart to become the market-leading product. Certainly, the market research we've done with physicians has suggested that navenibart will take a large market share of not only switch patients, so patients who are already on a prophylactic and switching off to go on to a drug like navenibart, but also newly diagnosed patients coming on to therapy for the first time. Fantastic. For the investors who are not super familiar with your phase III trial, could you elaborate on the trial design? Initially, you plan to start a three-month first, and then six-month cohort. Now, actually, you're going to start simultaneously. Can you tell us what's the advantage that it offers? Yeah, so we were able to include both the Q3-month and Q6-month dosing regimens in a single pivotal phase III trial. That trial was initiated in February of this year. I think the advantages that we see for bringing both of these dosing regimens forward is it gives patients and physicians more options, and I think creates the opportunity to capture the most market share by being able to offer both at time of launch. Certainly, our original premise before we were able to get in front of regulators around the world was that we might run these in two separate phase III trials. Of course, there's a cost savings to be able to do them in a single trial as well, not only operational costs for running the trials, but also as we think about other costs that we can have synergistic effects of running the two simultaneously. I see. Also, do you see six months and three months dosing regimen might target a slightly different patient population? In another word, how do you think physicians are going to balance the efficacy outcome to the treatment convenience if actually two different dosing regimens actually turn out to have a little bit different treatment outcome? Yeah, so it's interesting. There is great interest in both the Q3-month and the Q6-month. When we've done market research with patients, we've seen almost equal interest in the two different dosing regimens, which at first we found interesting because we originally anticipated most may want the less frequent dosing every six months. What we've come to learn is that many patients and many physicians might want to start navenibart every three months if that drug works for them, if navenibart provides the level of attack rate reduction that meets the needs of the patient, that then they might want to try the longer dosing regimen every six months. We anticipate that we might have most patients starting on a Q3-month and transitioning to a Q6-month. Great. How is the trial designed to show statistical significance for the endpoints? Yeah, so we have three treatment arms, three navenibart arms and a placebo arm. Each of those treatment arms will be compared individually to placebo. Also, the phase III trial started enrolling in the first quarter of this year. Can you provide some color on the enrollment pace? Yeah, so I will say, yes, so the trial started in February. We are now enrolling in both the U.S. and Canada and opening sites in the rest of the world presently. I will say we are quite pleased with the enthusiasm that we're seeing from patients and physicians. Everything remains on track at this point for early 2027 for top-line data. Great. Could you actually share some more details on the timing of regulatory filing on top of phase III success? Yeah, we haven't worked out those details or shared those publicly yet, but of course, we're going to be working very efficiently, as efficiently as possible to make sure that we can have this filed as soon after data as possible. There will be around 10 adolescent patients in the phase III trial. What's your regulatory strategy for this patient and also patient population, also pediatric HAE, given there is no placebo arm for adolescents? Yeah, so that design, so the adolescents, we will enroll 10 adolescents. You're right, they will not have a placebo control, and they will not be part of the primary analysis for the phase III. That was based on regulatory feedback that in order to have the adolescents in the label, we just needed to include them in the pivotal phase, but did not need to include a placebo arm for the adolescents. I see. Could you also discuss the market research you've done on the potential market penetration of three versus six-month dosing and also how your drug makes a difference across the HAE landscape? Yeah, so we think based on the profile for navenibart, it's a trusted mechanism. It's a trusted modality. So the mechanism and modality are the same as the current market-leading product, TAKHZYRO. We think that gives it a strong advantage as we think about going into the market and penetrating that market. In addition to that, the data to date has shown a very strong efficacy profile, very good safety tolerability. To date, our injections have not been associated with pain, which we think is something that's important certainly for patients. We think with that profile that we believe we can support with the phase III, we think that we have the opportunity to become the market-leading product and take share not only from products like the current market leader, TAKHZYRO, but also from the other categories as well. How physicians are receptive to make a switch to navenibart from TAKHZYRO, Takeda's drug for HAE, if both three-month and six-month cohort showing similar treatment outcome in pivotal trial from your early phase trial? Yeah, I think with data similar to what we produced in the proof of concept trial in patients, I think it's an easy conversation for a physician to have with a patient that's on TAKHZYRO. Same mechanism, same modality, but just much less frequent dosing. We also hope a better experience for patients in terms of no injection site pain. That's been a target as well for us. We think that's an easy conversation, and hence why we are bullish about our potential to really capture that market-leading position with navenibart should we be able to support that profile. Still early days, but would you like to discuss the commercial plan if you decided to by yourself? Also, are you open to partnership for future commercial path? Yeah, what we've talked about is that we intend to commercialize navenibart in the U.S. on our own, but we are considering what to do outside of the U.S. That could involve partnerships in Europe, could involve partnerships in Japan. That strategy is being discussed now. Great. Switching to atopic dermatitis for the OX40 antagonist program, this is also a competitive space with many approved drugs and pipeline candidates. What is the unmet needs you see there for your program? Yeah, I think atopic dermatitis is a very large market, but it's growing and growing massively. I think there's also a growing appreciation and use of biologics and mechanism-based biologics. Right now, DUPIXENT is clearly performing incredibly well in atopic dermatitis and serving patients well. However, there are about 40% of patients that don't respond adequately to DUPIXENT and drugs with that mechanism that target selectively a Th2 population of T-cell mediated disease. We see that remaining 40% of patients as a good initial target population for a drug like STAR-0310 that targets the OX40 pathway. OX40, one of the exciting pieces about OX40 is it has a broad effect on broad T-cell populations. We believe it can reach patients that may be inadequately controlled by drugs that target just one of these T-cell populations. I think the other interesting piece about the OX40 mechanism is the potential for disease modification. We're really excited to test that potential. What is the key takeaway on both safety and efficacy front from OX40 targeting strategy from a couple of late-stage programs? Yeah, so you're referring to so both Amgen has their rocatinlimab program, and Sanofi has their amlitelimab program. Amgen has released results from three phase IIIs in atopic dermatitis with rocatinlimab. Interestingly, their phase II-B, which was a well-controlled atopic dermatitis trial with their 300 mg every two-week dose of rocatinlimab, they saw efficacy on par with DUPIXENT in AD patients. However, when they went into phase III, they took that dose and cut it in half. They went to 300 mg every four weeks, which led to lower efficacy. They still hit their endpoints and showed strong effects in atopic dermatitis, but not as strong as they saw in phase II-B. I think that caused a lot of interest and concern from people in the space. I will say rocatinlimab was engineered for high ADCC, so high killing of T cells. That was in the engineering of that antibody because it was believed you had to kill the T cell to have the efficacy. I think what Amgen is trying to do is thread a needle, so balance the AE profile, the fever chills associated with ADCC, but maintain the efficacy. That was when we started our STAR-0310 program, knowing the ADCC activity of rocatinlimab. That was built into the design of our molecule to have a molecule that hit the receptor as hard, as potent as rocatinlimab, but without that T cell killing, to avoid the fever chills AE profile so that we could open up the therapeutic window, really drive the doses to drive the efficacy. That is where we hope one of the areas we hope that STAR-0310 will differentiate. Fantastic. In the upcoming initial results from your phase III in-house volunteer trial, what should investors be looking for? What kind of data sets do we anticipate? For example, will the Th2 biomarkers be included in this update? What we'll be looking at, there are two key sets of data we'll be focused on. One is the AE profile, the tolerability profile. We know from the rocatinlimab program in healthy subjects, they saw greater than 50% of subjects having fever associated with dosing. We're clearly going to be looking for a differentiation there. We also have engineered STAR-0310 for a very long half-life, so we'll be looking at PK because the idea with STAR-0310 is not only can we drive efficacy to greater levels, but we also can have very infrequent dosing. We'll be looking at that. We will be testing exploratory biomarkers. Of course, these are healthy subjects, so they do not have activated T cells. We'll be doing some exploratory biomarkers. Great. Maybe lastly, could you help us to understand the balance sheet and also lay out the most meaningful catalyst over the next 12 months- 18 months? Sure. Yeah, we ended the last quarter with just under $300 million in cash. That cash position will take us into mid-2027. Importantly, through major catalyst for the navenibart program, our lead program, beyond our top-line phase III data. Over the next 12 months-18 months, we'll have the data from ALPHA-SOLAR, the long-term extension with navenibart, so patients who have been on drug for 12 months-18 months. We're looking at both the Q3 month and the Q6 month regimen there. We'll have our phase I-A healthy subject data for the STAR-0310 program. Again, we believe that data will read on the potential for differentiation of that program. Beyond that, we'll be looking straight to the phase III data. Fantastic. Thanks for a very insightful discussion. Thanks everyone for joining us. Thank you.