Great. Good afternoon, everyone, and welcome to the next session at the Cantor Global Health care Conference. I'm Steve Seedhouse on the Cantor Biotech team, really glad to be joined by our next participating company, Astria Therapeutics, an exciting company that we launched coverage on when we came to Cantor. It's been a privilege to cover so far, and looking forward to all the upcoming progress. I'm joined on stage by CEO Jill Milne. Looking forward to the conversation. As has sort of been typical for me in these fireside chats at our conference, I would love to just pass you the mic to start for some introductory comments and overview of the current state of affairs at Astria and the outlook as we head into the end of the year here. Great. Yeah, absolutely. Thanks for having us. It's been a great conference. At Astria, our focus is on developing medicines to improve the health and outcomes of people with allergic and immunologic diseases. Our lead program is navenibart. It's a monoclonal antibody inhibitor of an enzyme called plasma kallikrein, which is a clinically and commercially validated target for the treatment of hereditary angioedema, a rare disease. We are currently in phase III development with navenibart. What has excited us about this program is the efficacy that we've seen to date with navenibart in our phase I-B2 trial, which demonstrated a greater than 90% attack rate reduction in patients with HAE for both our Q3 -month and our Q6 -month dosing regimens. Those regimens are currently being tested in phase III. We are actively enrolling that trial and on track for top -line data in early 2027. The second program in our pipeline is STAR-0310, and this is a monoclonal antibody antagonist of the OX40 receptor. We have some data coming out in a couple of weeks at EADV. We will be presenting an oral presentation in the late breaking session on our phase I-A healthy subject data. Very much looking forward to that as well. Thanks for that overview. We'd love to talk about OX40. There's been some news just recently with OX40. We'll start with HAE. Same day. Yeah, we can maybe come to that. Just in the phase III, I mean, how is enrollment going? Are you satisfied with the sort of guidance you've put out there for early 2027 data? How's the progress? Yeah, we are thrilled with the progress to date, really excited about the enthusiasm that we're hearing from patients and physicians. The trial is active now in the U.S., U.K., Canada, South Africa, Hong Kong, with European sites coming up, and also Japan sites coming up. So far, so good. We remain on track. Great. One thing that I wanted to clarify was, there's an additional cohort in this study, which is in adolescents, and that's an important segment of patients, of course, to address. Will that data be available with the initial top -line data release, or is that sort of running parallel and separate on a different timeline? It's running in the same trial, but as you're absolutely right, as a separate arm. We haven't yet indicated what data will be available with that top -line, but it is running concurrently with the phase III. OK. Is that enrolling as well right now? Yes. OK. Yeah. Regarding dose selection, in phase II, there was the additional dose at one month post-treatment initiation. In phase III, you've obviously selected the every -three -month and the every -six -month dosing regimens. Based on all the data that you're continuing to accrue, and you've presented some of that in the open-label extension study, are you comfortable with the phase III doses that you selected? Is this tracking as expected in terms of the long-term data you're seeing? Please talk about the rationale for doing what you did. Yeah, we remain confident in the doses we've selected for the phase III, both to support the Q3 -month regimen as well as to support the Q6 -month regimen. That confidence comes from the data that we've released to date from the ALPHA-STAR phase I-B/II trial, but also importantly from the ALPHA-SOLAR open-label extension trial as well. In addition, our QSP, or quantitative systems pharmacology modeling, also supports both of the Q3, Q6, and the doses selected for those. OK. In the adolescent arm that I mentioned, the dosing regimen there, I think, is 600 mg transitioning to 300 mg. What was the rationale for that in that particular arm? We think that the Q3 -month regimen will really be a huge improvement for adolescent patients with HAE to go to that infrequent dosing. That dose selection was selected based on the quantitative systems pharmacology modeling and based on previous data that led us to that, as well as conversations with health authorities. Just to follow up on the recent announcement of the Kaken partnership, first of all, I guess, what role will Japan sites and enrollment of Japanese patients play in the overall study? That has some implications also for the reimbursement as part of that partnership, I think. Maybe just recap the structure there and the expectations for how big of a role that region will play in the trial. Yeah, so Japan is obviously a region that we're very interested in. It's, you know, the third largest market behind the U.S. and Europe. It's actually a really interesting market in that it's really early in development. We think it's important to be there. We are really pleased with the partner that we've selected to do that with. From a phase III trial perspective, one important aspect of having a partner for us is really to raise awareness of the trial and also to engage the KOLs and treating physicians in Japan. That partnership included support for the phase III, so with regard to the percentage of patients we enroll in Japan. Just to give some color, I guess probably the best measure there is to look back at other trials that have run phase III and had sites in Japan. The most recent one at Dembry that was reported had about 9% of patients coming from Japan. There'll be a proportional cost that Kaken will cover as part of that. Got it. Will that be recognized just as revenue, like cost reimbursement? We haven't indicated how it'll be recognized yet, but by our next quarter, we'll have that assessment. OK. How are you thinking about Europe? We've seen some strategic transactions in the HAE space in Europe or Lido recently. Is that a market that you think is more amenable to a partnership as well, like Japan? Is that a region you think you can commercialize at Astria? Yeah, so what we've stated is, you know, we plan to commercialize on our own in the U.S. and are considering our strategy outside of the U.S. We've now revealed that strategy in Japan. Certainly, there's a lot of interest in the space. I think for us, we'll further explore what we think is right for the program and for patients and make a decision about that. Yeah, a lot of interest in the space. Yeah, back to the Japan deal, what was unique about that, of course, is you haven't even completed your phase III study yet. You're already licensing commercial rights at economics that match, you know, drugs that were pending approvals. I mean, how were you able to get that done on those terms? Yeah, we were, and you're absolutely right, because, you know, you'd most typically think wait until you have your phase III data because that will drive the best economics. We were really pleased with the process that we ended up running in Japan and how competitive it was to secure the economics that we did get for a pre-phase III. I think, you know, I chalk it up to the confidence in the program and the data that we've produced to date. I think, you know, also the interest that the Japanese partners had detected in the physician and patient population there for navenibart. Yeah, that's great. As you think about this market, I mean, it's a large market, HAE. A lot of patients have shown a propensity to want prophylaxis. That's a growing opportunity. There are some new launches recently in the space. You mentioned one in Dembry, also Danzirna, different mechanism there, a different approach from a knockdown standpoint. Just what are you looking for in these launches? I mean, obviously, sort of the willingness of patients to switch to a new therapy is one metric that would be critical to Astria down the road. The longer acting sort of nature of those antibodies relative to their predecessors is another. How, I mean, what's going to be important for you to see? What are you sort of hoping to see? Does any of this matter? Do you think, you know, in a vacuum, navenibart is going to succeed on its own merit? We'd love to get your perspective. Yeah, to start with the latter, I do think navenibart is going to succeed on its own merit. I think what we continually hear from patients and physicians is they want a therapy, a preventative therapy that has robust efficacy and can be dosed infrequently, with low treatment burden. We obviously are watching both of these launches closely. I can talk, you know, sort of out of both sides of my mouth. If their launches go well, it does speak to the switch population. I think if they go moderately well or not well, you could argue, is there enough differentiation from an every -month dosing to what we have right now with the market leader, Takhzyro, which can be dosed in some patients every month? We'll obviously be watching the dynamic and seeing which type of patients are switching. Personally, I am expecting them to struggle a little bit for that reason, because the differentiation reason. When we've talked to KOLs and when we were doing our work on the space, it was amazing to hear, maybe not surprising to hear that, you know, once monthly is not so differentiated from every two weeks, not enough to sort of overcome the stickiness of this market. The KOLs were aware of Astria and aware of navenibart. This was before you had even initiated your phase III study. How have you been, what have you been doing as a company, and how have you been able to sort of prep the experts in this space already years in advance of a potential launch? I'd love to sort of, you know, unpack the strategy there. Is it just the product profile speaking for itself, or how have you tackled it? Yeah, so I'm really proud of the work our team has done here. That work has started from day one when we first started working on this project in this area, to really understand what patients wanted and what physicians wanted in a product. We've had a very active open dialogue throughout the evolution of Astria from the time this asset became ours. I think that's paid off well. Importantly, the target profile that we have for navenibart is something that's pretty unique and special in this space, to have something that is a trusted mechanism, a trusted modality that so far has produced efficacy that is on par with the market leading products and also with a very low treatment burden that's really a step change from anything that's out there right now. I think helps support the interest. I think saying efficacy is on par with the market leaders may be a little too humble, because the efficacy to us looks quite a bit better from phase II. Hopefully, that can be replicated in phase III. Speaking of phase II, what future updates are we going to get from the long-term extension study that's ongoing? We've gotten one. The data looked great. On what cadence and when would be the next update? Yeah, we haven't indicated yet when the next update will be, but I can tell you we'll be taking data cuts from that ALPHA-SOLAR extension trial on an annual basis, and would expect to continue to share data from that. We agree that data has been great. It's really great to see patients engaged in that trial and staying in that trial. I think it speaks to the benefit that they're getting from navenibart. In addition to the efficacy and the convenience, also, the injection site reaction profile looks very mild for navenibart compared to at least Takhzyro. Can you just maybe walk through, I mean, what is that reaction and the burden on patients and sort of how important is it in your experience in talking to the experts in the field? Why is it so much more mild for navenibart? Is that a feature of the drug that was sort of built in? How much impact do you think that could have ultimately on patient preference? I think that's really important from a patient experience perspective. I can tell you when we first started this program back in early 2021, when we were talking to patients just to understand the HAE landscape, one thing we were surprised to hear is about how painful injections were with Takhzyro. It struck us. We hadn't anticipated to hear that. When we started to work on navenibart and work on the formulation we would ultimately take forward, we took that into consideration. How could you improve this to improve that patient experience? I can tell you hearing some patient stories about how they have to psych themselves up to give the injection. It probably speaks to why there's only a prefilled syringe in the U.S. For Takhzyro, so patients can control the rate of injection, where an autoinjector would be a faster uncontrollable rate that you're injecting if it's a stinging sensation. That's not a pleasant experience. We believe that could be due to the citrate buffer that's in the formulation for Takhzyro. We actively worked to develop a formulation that was very patient-friendly and could support a no-pain injection. That's sort of what our mantra was as we were developing that formulation. It seems to have played out. That's great. That's on the tolerability front. On the safety front, just thinking about the Danzirna label in particular and some of the sort of class labeling features, have you guys seen any effect on platelets? Have there been any hypersensitivity reactions or anaphylaxis in any of your studies? Was no effect on platelets, no hypersensitivity anaphylaxis, and also no elevation of liver enzymes, as was also in the label. OK. I mean, do you think that just by virtue of that, the data will speak for itself and that will afford you a differentiated label if you replicate that in phase III? Or is the FDA kind of a stickler on some just class labeling? If you look across the different labels, there are differences. I don't think it is a class label. Danzirna has a different mechanism, different modality as well. We don't anticipate that would be something unless we see something from a safety perspective in our phase III. OK. Maybe we can talk about OX40 as well. It's an exciting space. The amlodipine phase III AD results were just announced. Would love if you're comfortable just to get your perspective on sort of the outlook for OX40 as a mechanism in AD and beyond, and maybe updated thoughts post that data. Maybe we can start there, and then we can discuss the asset and the history of the asset and your plans for it. Yeah, of course, the rocatinlimab first phase III data was reported in a press release this morning. We saw that. I think from an OX40 perspective, what that data showed is both dose groups hit their endpoints, so showed efficacy in atopic dermatitis. There was a decrease in signal compared to their phase II-B trial. Obviously, we're looking forward to learning more about the patient population and how that might have been different from the phase II-B, but also understanding, I'm sure there are going to be later time points from that trial. If you saw the data, it appeared that they hadn't reached maximal efficacy, which was something we anticipated for them. This was, of course, replicated by rocatinlimab as well. We know the OX40 mechanism has a slower onset. You can see that there. The efficacy hadn't plateaued on either dose group in this data release today. We'll be interested to see that. I think OX40 is a really intriguing mechanism that has a lot of potential. I think being first in class comes with challenges in a new mechanism in disease areas such as this that are highly competitive. Learning from rocatinlimab and amlitelimab and how these trials have run and the learnings from these trials can help influence in a positive way those of us like STAR-0310 and how we design a proof of concept trial. I think we can all appreciate the premise in immunology that we've seen time and time again, whether it's TNF or IL-17. There's another, it's like the third or the fourth generation IL-17, big data coming this month in HS. It shouldn't be surprising that the first movers are going to leave something on the table from a molecular design standpoint that the Astria of the world can improve on. Can you just recap what are the features of STAR-0310 that you've built into that molecule and why you think it'll be better than some of those first generation molecules? Yeah, to start, we decided when we got interested in the OX40 space to target the receptor, you know, as opposed to targeting the ligand. The reason we chose to target the receptor was we believed that targeting the activated T cells was the place to go, because it's the activated T cells that only express the receptor. Those are the cells that are driving the pathology and the disease state, whether it be atopic dermatitis or another disease where OX40 plays a part. Just out of the gate, that was important to us. We thought there'd be potentially lower, you know, sort of off-target, off-T cell effects that could lead to safety or tolerability. Next, we designed a molecule that had low ADCC. As we know, rocatinlimab was engineered to kill T cells. We believe that has translated to the fever, chills, the ADCC-like effects that they're seeing in the clinic and has, you know, we believe caused them to leave some efficacy on the table. Our goal was, you know, if we had no to low ADCC, we could open up that therapeutic window, drive dose, drive efficacy to greater levels. We've also engineered this antibody to have a very long half-life. The idea being the combined potentially improvements in efficacy and that long half-life could allow us to really drive the potential of the molecule. We have our phase I-A healthy subject data coming out in a couple of weeks, and hopefully, that data will read on some of these aspects. Yeah, I mean, typically with phase I-A data, maybe there's not much to learn. Here, I think there are other instances, I think, in INI recently where there's been a lot to learn from phase I studies because the mechanism is validated, right? You have the late-stage efficacy data from some precedent. I want to just walk through some of the different maybe potential aspects of the data that we could see and just get your perspective on whether I'm thinking about it reasonably and maybe how you would frame some of these data points. First on PK, obviously. Based on preclinical data, there was a 26-day half-life in non-human primates. That would be expected to be longer in humans, maybe up to five-fold longer. Do you think that you'll be able to establish that the PK could support like every- six-month dosing in humans? What do you think you could establish already in phase I-A in terms of potential dosing intervals? We believe the data will give us an indication of whether we can support every -three-month or every -six-month dosing. On PD, is there a way to assess pharmacodynamics in this study in healthy volunteers? Maybe even from the standpoint of just sort of piecing together PK, PD from other OX40s and what levels were needed to be reached? Can you adjust for the potency of your antibody? I would love your perspective on how you're thinking about extrapolating this phase I-A data to knowing if you're at therapeutic levels. Yeah, unfortunately, not all programs have reported healthy subject PD data. It's hard to compare directly across to that. As you say, because there are molecules ahead of us that have clinical efficacy, we have a good understanding of, and we know potency of our molecule in vitro. We know potency of those molecules as well in vitro. You can build models that will give you a read of, have we achieved drug levels that we think will drive efficacy to levels that are important? This data is going to be used to build a QSP model to hopefully inform on dosing regimens and where we think we can drive efficacy in terms of every -three -months or every -six -months. Great. The other important safety and tolerability. You mentioned some of the potential areas of differentiation given the molecular design, the enhanced ADCC of rocatinlimab, and the impact, I think you mentioned, on chills. Is that something you can tease out already in phase I-A, or are we going to have to wait? Yeah, for sure in phase I-A. In fact, that is an easy thing you see upon dosing is if a molecule has ADCC, you will see that fever and chills. In the rocatinlimab phase I-A healthy subject trial, they saw, you know, greater than 50% of subjects had experienced a fever or chills. OK. I guess the big question, which is assuming these data support the product profile that you're hoping for, what's the next step? I mean, even after this morning, how are you thinking about atopic dermatitis maybe strategically or other potential indications for this drug? Yeah, that's a great question. For us, it's getting our data, looking at the external landscape, and determining what the best path forward is for STAR-0310 and in what indication. I think it's clear that there is efficacy of this mechanism in atopic dermatitis. Is there a way to drive that efficacy deeper and faster? I think our team has some ideas about that. OK. Just to close, I want to go back to HAE. It's a market that we have a lot of data on historically. There are a lot of drugs approved, and these new launches we'll be tracking. Do you think there's going to be big changes in that market over time in terms of proportion of patients on prophylaxis? Pricing is maybe a big one. Anything else? Do you think you have a handle that that market's pretty predictable and stable? What you see today will sort of be a similar landscape to when navenibart launches? Yeah, so I think the market is going to evolve. Clearly, with the other products coming to market, we're going to see some evolution and movement of patients. I think some of the older drugs potentially will begin to take less and less market share. Some of the more burdensome drugs that are dosed two or three times a week, I think, become probably less interesting in the marketplace. I think, as we see it, the market will likely evolve to the agents that have the best efficacy and the lowest treatment burden. We see navenibart playing a big part in that. I think in the U.S., there are probably about 70% of patients on preventative therapies. That will probably continue to grow. Certainly, there's more room for growth in Europe and a lot of room for growth in Japan in terms of patients going on to preventative therapies. Quite frankly, in Japan as well, our understanding of the patient population there is there's only about 20% -2 5% of patients have been identified. We think there's a lot of growth that's going to happen in that market. I'm expecting there'll be another oral on the market. There are now oral on-demand therapies. Intellia's gene editing product could very well be on the market. Do you think those will have sort of large transformative impacts on the market, particularly on gene editing? Does that feel like it could be a niche product for the most part? Yeah, I think it'll be, you know, my guess it'll be a more niche product. The reason I say that is this HAE is a place where there are trusted modalities that work really well. What we haven't seen from gene editing yet is, you know, it is not a cure. I think the question will be, is it worth, you know, is the risk-benefit there for gene editing? I think the orals, there'll always be a place in the market for orals. We firmly believe that when you have an agent that can be dosed as infrequently as every -three- or six- months, you probably start to think about patients who are going to an oral for convenience might be better served by something they can think about 2 x or 4x a year. Anything we didn't cover that you'd flag that would be important to highlight for investors that you'd be expecting either away from Astria or anything you have cooking in the oven at Astria that you'd be announcing or updating folks on in the next six to 12 months? I think for us, it continues to be about execution and doing what we say we're going to do. We've done a good job at that so far. I think advancing to high-quality programs. Great. We really appreciate you being at the Cantor Conference this year. Thanks so much for the discussion. We're looking forward to the phase I-A OX40 data that's upcoming and all the progress that you'll be making in the years ahead. Thank you. Good to have you here. Yes.