Hi, everyone. My name is Liisa Bayko, biotech analyst here at Evercore ISI, and really pleased to be doing a fireside chat with Jill. She's CEO of Astria. Astria's a company that's working on hereditary angioedema, and I think they have a really nice solution, which actually Seema on my team coined as long-acting Takhzyro. And so, we're, we're TM-ing that, by the way. You heard it here first. So, I think that really kind of summarizes it. This could be a once every three months or six-month option for patients, and I think they're off to a really, really good start with this. So, tell us about the history of STAR-0215. Actually, first tell us a little bit. I I mean, you've kind of evolved, Jill, from sort of where you were before. Tell us about kind of the new Astria's- Yeah ... or what your mission is. You've got more actually than just STAR-0215, but- Yeah, for sure. So, our focus at Astria has been to advance what we call first choice products for patients living with allergic and immunological diseases, and what we mean by first choice is that patients and physicians would choose our products because of the strong competitive efficacy profile, the low treatment burden, and the favorable safety and tolerability profile. We've chosen to focus our pipeline on established mechanisms initially, and so what we mean by that is mechanisms that are clinically validated, but where we believe we can advance a best-in-class program, a first-choice program. And certainly STAR-0215 fits very well with that strategy, as well as our second program in the pipeline, STAR-0310. You've done some really cool things to optimize STAR-0215. So you picked it up from a company and you did some tweaks, and now you could have a long-acting version. Can you just kind of give us just the brief highlights? Yeah, so we acquired STAR-0215 from a stealth biotech company called Quellis when it was in its early preclinical stages back in 2021. And what STAR-0215- Yeah ... was it's an antibody that's been engineered with the YTE half-life extension technology. And what we saw in the potential of STAR-0215 is the option to offer patients very infrequent dosing with STAR-0215 to prevent attacks that occur in HAE. So, as you said, as infrequent as dosing every three or six months. Is the YTE modification something you can really do to any antibody? Certainly, it's been applied now to a number of antibodies, which is exciting to see. It doesn't always work, so it's important to, you know, establish that preclinically and then, of course, clinically, which we've done now with STAR-0215. What's the IP for this product? So we have. We wholly own a provisional patent application that should have life through 2042, and that's without patent term extension, which we would anticipate getting. We've also filed on the dosing regimens for STAR-0215 as well. Tell us a little bit more about the product profile you're going for? Yeah. So we are... Our vision for the product is to be first choice preventative treatment to prevent attacks occurring in hereditary angioedema patients. We expect, you know, strong efficacy with a dosing frequency of every three months and every six months. Our intention is to advance two different dosing regimens so that patients can choose which one fits best with their lifestyle. Why would you want it every three months if you can have every six months? You know, it's interesting. We've done some pretty extensive market research with both patients and treating physicians, and what we see is that there is a strong interest from both patients and physicians in an every three month option- Hmm ... and an every 6-month option. That's so interesting. You know, we haven't, and this is something we'll do going forward, is dig into that market research data in more depth and perhaps go back and do some more to understand that. But, as I talk to patients and hear their concerns just in, you know, their treatment, I wonder if there's some, you know, perception that every three months will keep me better controlled than every six months. And you know what? I think what we intend to advance is three-month and six-month treatment options that offer, you know, the same level of attack rate reduction, and so that will be part of the, you know, an education process for us as we advance these product presentations. How confident are you in the ability to get to every six months? The data to date gives us strong confidence that we can support the every six month dosing regimen, and so that's based on our clinical PK data that we've generated to date and our PK modeling data, which shows that we can keep trough levels of STAR-0215 above what we think is the critical threshold to keep plasma kallikrein levels suppressed. And that's the PK data correlates very well with our PD data, showing that suppression of plasma kallikrein activity. You're not the only company going for infrequent dosing. Mm-hmm. So, how do you think within kind of the sort of next wave of innovation, which is really iterating on this concept of longer duration therapies with less, you know, more convenience, how do you, how do you feel like you distinguish and differentiate within, within those? Yeah. We believe that STAR-0215 has the potential to be a first choice in the treatment of HAE, and we think that's for several reasons. It is a competitive landscape. There are a lot of products, and this has been a great thing for patients, but I think what we have in STAR-0215 is pretty special. So, the data we've generated to date shows really strong clinical profile from the perspective of drug levels, PD biomarkers suggesting that we can keep plasma kallikrein levels suppressed and keep attack rate reduction down, and at the level of the market leader, Takhzyro. I think importantly, you know, when you think about patients and physicians, there's a lot of comfort with k-... STAR-0215 from the perspective, it is targeting an already proven, mechanism, it proven safety, you know, from a safety perspective and an efficacy perspective. You know, the market leader is a monoclonal antibody that inhibits plasma kallikrein, just like STAR-0215, and so there's a lot of comfort with that. But it, ours has been engineered for a very long half-life. I think, you know, that, I think, gives us strong confidence that this will be a very competitive product going forward. The data suggests we can, We get very rapid onset of effect, which is important for patients with this disease. So our clinical data we presented at ACAAI just last month shows that within 11 hours of dosing with STAR-0215, we get to levels that suppress plasma kallikrein sufficiently to suppress attacks based on what's known out there, and that's important for patients. When you take a drug, you want those attacks to stop as quickly as possible. I think also we've formulated STAR-0215 in a citrate-free buffer, specifically to try to eliminate the pain that's been associated with I have heard it's quite uncomfortable. Yeah, and we heard that a lot. We've spent a lot of time as we've been developing the STAR-0215 program, talking to patients to understand what their interests are in a new product, and we heard again and again about the pain associated with injection, and so we went to great lengths to make sure that that wasn't going to be the case with STAR-0215. And yeah, so, I think with all of that, we think that STAR-0215 has a lot of potential to be that first-choice preventative therapy. I think when we visited you on our bus tour, there was a comment that maybe you could also get to a once yearly dosing. Is that a stretch, or is that kind of something you're actively working on, or is that aspirational, or? So we haven't ruled out- Okay ... a once-a-year dosing. Okay. However, our focus is on a Q3 month and a Q6 month regimen- Okay ... because what we hear from patients and treating physicians is a lot of interest in a 3-month and a 6-month dosing regimen. Would this be self-administered? Yes. Okay. So that, that's really important. We wanna give patients the opportunity to self-administer, so that, that's going to be part of it. Tell us about the presentation. Like, what is the, what's the volume? How viscous is it? You know, will this be an auto-injector, or what will be the presentation? Yeah, so, we're actively exploring the administration options right now. Auto-injector is absolutely on the table. So, for instance, a 300-milligram dose could fit easily in a single auto-injector. And so that's something that we're actively considering, and we have a, you know, 150 mg/ml concentration right now in the formulation we have. We've done some formulation optimization, and I think we can go up from that concentration, but we're already comfortably in a range where we can fit a maintenance dose in that, in a single auto-injector. Tell us about, I know you've had some recent data. Maybe you can just talk about that, and then, we'll start there. Yeah, so the recent data that we presented at ACAAI was from our phase 1a trial in healthy volunteers, where we explored PK of single doses of STAR-0215. So, we looked, of course, at safety and tolerability, pharmacokinetics and pharmacodynamics, and importantly, the data that we generated there, we were able to put into a pharmacometrics model to start to look at potential dosing regimens to take forward in patients. And so what that data has shown is that we get very rapid onset of effect of STAR-0215. It's durable for a long durations of time, and that the modeling that we've done with that human PK data and PD data suggests that we can support both a three-month dosing option and a six-month dosing option. What's next now? We are currently in a phase 1b/2 trial in patients with hereditary angioedema. We expect to report initial proof of concept data in patients in Q1 of next year. With positive data there, we intend to go to a single pivotal phase 3 trial in HAE patients. Right now, we have stated that that would initiate in Q1 of 2025, but you can imagine, we're looking at all opportunities to accelerate that timeline. Great, so just back to the data that's coming, what exactly are we gonna see in that? How long are you dosing? I guess, which doses? Is it- Mm-hmm ... both the 3-month and the 6-month, and how many patients? You know, what are you gonna be looking at exactly? Yeah, great question. So, we have built into the Phase 1b/2 trial, which we call ALPHA-STAR, an interim analysis, and that's the data that we'll be sharing, and so that data will report on efficacy, so attack rate reduction, attack-free, percent attack-free, PK, PD, safety tolerability, of course, as well. And what we'll have is data, efficacy data from both single and multiple doses of STAR-0215 in patients, as well as 3 and 6 months post-dosing in patients. You'll have reduction in, like, attack rate or- Mm-hmm ... that kind of stuff? Yeah, so we'll report reduction in attack rates, as well as, attack-free, percent of patients attack-free. Okay, okay. And you're taking two doses forward, as you mentioned. Do you think, do you expect to see a difference in attack rate between these doses or anything along those lines? Our goal is to have robust efficacy with both of those dosing regimens. Okay. So likely, the Q6 month dosing regimen will be a higher dose than the Q3 month. But our goal would be to have both of those provide robust attack rate reduction- Okay ... that's comparable, so that a patient isn't giving up efficacy in order to support the longer duration. Okay. But you said that you shouldn't be doing that anyway. Or is it a maybe? Like, why is... I guess I'm just trying to understand, there's a perception from patients- Oh, I see. Yes. that they might give it up. I think- Are they actually giving up efficacy? So we don't believe they will be- Okay. with our 3- and 6-month dosing regimen as we envision them, and that's something that we'll have to work on, I think, from a perception. It's just been interesting to us in market research- Yeah ... that there is a similar interest in both. 'Cause you might- How, what's the extra cost it'd happen to bring two doses forward versus, you know, what? Is it a lot bigger of a? So, that is a great question that we are working through right now. So you can imagine the development costs of taking two dosing- Right ... regimens forward, larger Phase 3 program. So- Right ... certainly more patients. You know, I think there's also an element of time, right? It's clearly faster with a shorter dosing regimen than it is with a longer dosing regimen, and so we are looking at ways to optimize our phase 3 development strategy so that we can get to market as quickly as possible and get this drug in the hands of patients as quickly as possible. So, there may be a staggered approach to getting these, both of these dosing regimens forward. What does that mean? You know, as we get the data from the ALPHA-STAR, we will certainly be consulting with regulators around the world to understand what the best path is forward in phase 3 for us to support both the 3- and 6-month. So, it could be that we go first with the Q3 months into phase 3 as quickly as possible, and stagger in the- I see ... the Q6 month. Okay. We'll be working with regulators to understand what the best approach is for patients. So, how are these studies just six months in duration? We anticipate that the Q3 month would be six months in duration, too. Because it's interesting, 'cause with the Q6 months, in a way, do you have to do a year just to kind of- You could imagine that you might have to do a year of treatment period- Yeah ... to get 2 doses in. Right. Yeah, right. Yeah. Right. So- You and I were kind of like touching upon this. So Seema, we were actually having an internal debate on your data because you didn't give the second dose for 6 months. So Seema and I were having a little, like, tete-a-tete about, like, if you really had proved the 6 months. So I won't tell you who was on which side of that. Well, I think one thing to keep in mind is, you know, this is, you know, HAE has been... Takhzyro really has laid such a great, you know, framework for us in terms of looking at PK/PD efficacy relationships, and so the modeling data here is incredibly powerful. And so when you model data for the Q6 month and the Q3 month, you can see the data that we've shown in... We've presented previously on our modeling shows that Q6 month can maintain drug levels at sufficient C troughs to keep plasma kallikrein suppressed at levels that should translate to very good attack rate reduction. We had ADRx here yesterday. Mm-hmm. It was really interesting because they kind of are covered for, you know, 3 months and 6 months, not a year, but 6 months. Then, they talked about actually dosing even higher now to try to get really, like, 0 attack rate kind of strategy. Mm-hmm. So anyway. Yeah, no, I think what we're excited about is, I think with these longer durations of keeping plasma kallikrein suppressed, we can keep more patients attack-free. Right. You see that when you... You you... You know, we've seen that going from, you know, every two-week dosing with Takhzyro to something that's dosed every four weeks. You can keep patients... You keep those plasma kallikrein levels suppressed for longer periods of time. Right. I think, you know, one thing, I think from our perspective, you know, we'll be interested to see how ADRx advances at higher doses, and whether they'll be able to get to a six-month regimen based on where they are now. Right. I mean, we've seen a very, for us, with STAR-0215, we've had a very clean safety profile, no issues with dose escalation, no effects on liver enzymes. So, I think a clear path, you know, we hope, a clear path from a safety tolerability profile. I don't wanna end this without addressing your new compound. Yeah. Maybe we can talk about STAR-0310. Yes. Yeah, so we're very excited about STAR-0310. It's, 310. Yeah. We internally debate how best to say, I think 310 is faster. All right. Let's go with that. STAR-0310 is an anti-OX40 antibody that we think has the potential to be best in class among the OX40s in the treatment of moderate to severe atopic dermatitis. We are in preclinical development with STAR-0310 right now. We expect to file an IND by the end of next year and be in the clinic as soon as possible. It's an exciting area. I think the OX40 mechanism has such great potential broadly, not only in atopic dermatitis, but very broadly in a number of T-cell mediated diseases. There's some controversy with the OX40s. What's the what? ... Oh, it's- Can you touch upon that? Yeah, so there are two programs ahead of us. One that targets the OX40 ligand, that's amlitelimab from Sanofi, and there is another antibody from Amgen, rocatinlimab, which targets the receptor just like we do. The rocatinlimab is an antibody that was designed to be afucosylated, which increases ADCC, and depletes T cells, as opposed to preserving T cells and just inhibiting the effects. And so that can be associated with some, you know, negative effects with cytokine release, chills, pyrexia, and they have seen that in their clinical trials, although they've reported great efficacy in their atopic dermatitis phase 2s. And amlitelimab targets the ligand, which is more ubiquitously expressed. So, what we like about the receptor approach and what we're doing is that you're selectively targeting activated T cells. What we've done differently than rocatinlimab is our antibody was not designed to be T-cell depleting. Okay. It was designed to be T-cell preserving. Okay. So, we believe we may win on, you know, from a favorable safety tolerability profile. Also, we've engineered STAR-0310 with YTE technology to provide, hopefully, the opportunity for less frequent dosing. And we've also designed it to be high-potency antagonist of the OX40 receptor. Would this also be an every, like, Q3 month, Q6 month, or? Yeah, so we think potentially, Q2 or Q3 month. Okay, okay. As we advance into the clinic, we'll be able to refine that prediction as well. Okay, so give us a glimpse into 2024 for Astria as we wrap up. Yeah, it's gonna be a busy year for us. We'll have our initial patient data from our STAR-0 215 phase 1b/2 trial in HAE. We'll be working toward getting a phase 3 up and running, assuming positive data from that trial. For STAR-0 310, we'll advance through an IND and file an IND by the end of the next year, is expected, and then be in the clinic soon thereafter, so big year. Excellent! Thanks, Jill.