Good morning, everyone. Thank you for attending Jefferies Healthcare Conference. My name is Kelly Zou, one of the biotech analysts here. We are very pleased to have Jill Milne, CEO, and Dr. Chris Morabito, CMO, from Astria join us for this fireside chat session. Welcome, both. Maybe we can start off with introduction of the company and also the strategy of developing first-choice therapeutics in allergic and immunological indications. Yeah, absolutely. Yeah. Well, thank you for the invitation. So our focus at Astria is to develop first-choice products in for patients with allergic and immunological diseases and to improve their health outcomes. And what first choice means to us is that both patients and physicians will choose our products first, based on competitive efficacy, low treatment burden, and a good safety and tolerability profile. The products in our pipeline are based on established mechanisms that are clinically validated, but where we believe we can advance a best-in-class product. And very much in line with this strategy is our STAR-0215 program, which is a monoclonal antibody inhibitor of an enzyme called plasma kallikrein. And plasma kallikrein is a clinically and commercially validated target for the treatment of hereditary angioedema, a rare, life-changing, and, at times, life-threatening disease. We've just recently released positive proof-of-concept data with STAR-0215 in patients and are advancing into phase III. Also in our pipeline is our STAR-0310 program, which we believe can be a best-in-class agent for the treatment of T-cell-mediated diseases, such as atopic dermatitis. STAR-0310 is a monoclonal antibody antagonist of the OX40 receptor, a mechanism that is also clinically validated and where we see great potential. Terrific. Maybe let's dig a little bit deeper into 215. Would you mind to actually elaborate on the clinical data achieved to date, and also, how do- how does it compare to Takeda's Takhzyro, which has the similar mechanism of action? Yeah, great. So, 215, as Jill said, is a monoclonal antibody against plasma kallikrein that's been specifically modified for a long half-life. And also, as Jill said, we've now carried this through not just phase I, but also phase II proof of concept, and I'll talk about those data in a second. Let's start with phase I. This was a healthy volunteer trial, and what we showed in that trial was that, in fact, not only do we engage plasma kallikrein and meaningfully inhibit its activity, which is what it should do, the half-life of this molecule is about three months long. And that certainly is compatible with our vision to give this very infrequently, once every three months and once every six months to patients, in a meaningful way that will profoundly impact their lives by reducing attacks. We took this into Phase 1b/2, the 1b/2 trial, which is called ALPHA-STAR. This is our proof-of-concept study in adults with hereditary angioedema, and that's in fact what we've seen. This is an open-label trial testing three cohorts, single and multiple doses, with up to six months of follow-up from the last dose, and we're seeing profound impacts on efficacy. We're seeing a 90%-96% reduction in mean monthly attacks. We're seeing up to two-thirds of people who are attack-free. We're seeing significant reductions in the burden of disease in terms of the need to use rescue medicines, the severity of the HAE attacks. And importantly, we're seeing pharmacokinetics and pharmacodynamics that support, ultimately, this profile that we've, that we've aimed for, which is rapid onset of action and durable prevention of HAE attacks in patients. On top of this, the safety data that we've obtained, not just in healthy volunteers, but also in patients, continue to support the first-choice attributes of the molecule that Jill described. We're not seeing injection site pain. We're not seeing any side effects here that warrant any concern. In fact, the safety data so far are very favorable. Comparing to lanadelumab or Takhzyro, currently the market leader, plasma kallikrein inhibitor, standard half-life of a couple of weeks, and they're dosed every two weeks in the majority of people who have this. So that's 26 x per year. Our data tell us that we're dosing 4 x per year or 2 x per year. Very different. And we're doing that with potential best-in-class efficacy and with a low risk of pain. We've seen no pain relative to the 52% of people who take Takhzyro, who experience pain with injection, and not seeing any signals that make us concerned about safety. Okay, terrific. Could you also share on Takhzyro, what is the current revenue number and the projected market size? And, what do you think the STAR-0215 can do in the future? Yeah, I'll take that one. So, HAE as a market is, large, and it's growing. So in 2023, it was just over $2 billion as a market for preventative therapies and expected to grow, well over $4 billion by 2028. So as Chris mentioned, Takhzyro is the current market leader as a preventative therapy and did, sales just over $1 billion last year, and that has been growing year-on-year. And we believe the profile of what we have in STAR-0215, we hope will position STAR-0215 to ultimately be the market leader. ... Terrific! And for the patient data from Phase 1b/2, you guided another update in fourth quarter of this year. Could you set expectation on what should be the focus of this update? And also, what is expected follow-up duration for Q3 mo- Q3m and the Q6 months cohorts, respectively? Yeah. So we do plan to release data from the ALPHA-STAR in the second half of this year, and that data will be the complete follow-up for all of the 16 patients in the initial ALPHA-STAR study. So Chris had mentioned the data that we released, the proof of concept data in March of this year. That was an interim analysis of ALPHA-STAR. So the data we'll release later this year will be the full analysis from all 16 of those patients. And so we'll have data on efficacy, on safety, tolerability, PK, and PD for up through 6 months following the last dose of all of those 16 patients. Okay, terrific. You also guided a phase III trial for Q3, dosing is expected to begin in the first quarter of next year. Could you lay down what is pending between now and the start of the trial? How has been the discussion with regulatory agency? Yeah. So propelled by these data that we just presented not too long ago, we have a lot of conviction that 215 could be given to patients to prevent attacks when administered once every 3 months, and also once every 6 months. Our aim is to get this drug onto the market as fast as we can, and to get this in the hands of clinicians and patients in order to make a meaningful impact in their lives as quickly as we can. The fastest path is the 3-month phase III first, followed by a 6-month phase III second. And we are certainly in plans now to do both, and to do them as I just described. We're working today on finalizing the protocol and, working through agency interactions, to obtain feedback in order to finalize that protocol. Once that feedback is obtained, the protocol is finalized, then we take it to sites around the world and get those sites initiated. We're currently guiding to a Q1 Phase III start, but are looking for every opportunity to accelerate that into Q4, so that we get started before the end of this year, and we should be able to provide more information about that in the next few months. Okay. So investors are very focused on the Q every three months and every six months approval strategy. So in terms of timing, what kind of information for the Q3m you would actually need to think about every six months strategy? Right. So, our aim is to start enrolling the Q3 months, as I said, Q1, maybe earlier, maybe starting by the end of this year. And the goal would be to get that trial initiated, enroll, fully enrolled as fast as we can, potentially 12 months, for a global enrollment into this trial, 75-100 patients. And we want to do that unencumbered by competition from our own program. And that means waiting until we're close to fully enrolled, if not fully enrolled, in the Q3 months before we start enrolling in the Q6 month. Get the trial fully enrolled, get the patients in the treatment period, get those data, get it to the market as fast as we can, and then while we're confident we can enroll the Q6 month trial, get that study started. Are you open to partnership on this program? Yeah. So what we've stated is that we intend to commercialize STAR-0215 in the U.S. on our own and are exploring potential partnerships outside of the U.S. and really haven't settled on what our ex-U.S. strategy is yet from a partnering perspective. I see. And, so, pending the phase III trial design in details, but, do you have, like, a projected timeline for top-line data? Yes. For the Q3 month phase III, we expect top-line data by the end of 2026. Okay, great. HAE is a very active space, so we have seen, like, different modalities and the mechanism of actions under clinical development. For example, like, an oligonucleotide and also, like, a genetic medicine, and also new target. Could you actually walk through each and how do you think about the competitive advantage of 215? Right. So starting with STAR-0215, established mechanism, plasma kallikrein inhibition is familiar to clinicians and to patients. And we now know from Takhzyro that this targeting this particular pathway is safe. Patients tolerate it well, minus the issues with Takhzyro itself, with injection site pain and the frequent administration. It's a monoclonal antibody, and we are, as a clinical community, very familiar with monoclonal antibodies. We know what they do, we know how they affect the body, we know they do not impact the genome, and that's critically important. And now, looking at the competitive space, we have seen some good data, some interesting data that's come out from the competition recently. Garadacimab last year presented data on a Factor XIIa inhibitor, which is a valid mechanism, now clinically validated, and has potential that they could seek or get approval for launch in the US and outside the US this year. That's once monthly. No better than once monthly, just once monthly, but it will have a good impact on attacks. So good once monthly option there, which is better than Takhzyro. Donidalorsen from Ionis just released some data last weekend, which is their phase III data, where they tested a Q4-week regimen once monthly and a Q8-week regimen, twice monthly. And the short of that is that the data under impressed. The Q4-week data looks a little bit not quite as good as garadacimab, looks a little bit less effective as lanadelumab. Once monthly, some patients might like that, but it takes a long time to actually impact the disease itself. The Q8-week performed as well as Orladeyo, so oral efficacy could work in some patients, likely will not be something that people will go to immediately. So we don't expect there to be... That's not a Q8-week, it's not a Q2-month drug. It's likely a Q4-week drug, going to compete against garadacimab, going to compete against lanadelumab. Intellia just had an update this last week. This is a gene-editing program, so the drug is specifically designed to edit the genome of people who have this disease. There will be off-target activities. We don't know what that means yet. We will not know what that means for many, many years. We've seen now 10 patients' worth of data in an open-label study have good impact on efficacy, and so far, the drug appears to be well-tolerated. It, too, takes a long time to be effective. It takes about four months before you see true efficacy with this drug, but long-term follow-up looks pretty impressive. I think the outstanding question will ultimately be safety, commercial viability, and then how comfortable will people be with a drug that they're not familiar with, that has the potential to edit the genome in a space in which there are valid options, like what we think 215 will ultimately be. So in short, we're really excited about the ability of 215 to compete. Three months, every three months, every six months, monoclonal antibody established mechanism, I think we're in a really good position. Very insightful. And also, could you share with us the physicians' feedback on the clinical profile for 215 to date, especially the ones on the clinical trials, and how do they compare and contrast it to other therapeutic modalities in HAE? Yeah, it's a really interesting question, and thanks for asking that. You know, we get a lot of word-of-mouth positive reinforcement about what we're doing. Patients like it, clinicians like it. They like the profile a lot. But the proof actually comes in our ability to enroll the 201, the phase 1b/2 proof of concept study, at the rate in which we enrolled it. We anticipated that we would be, at this point, sharing data mid-year 2024, and we actually accelerated that by a full-quarter. We enrolled a study almost entirely in the U.S. and in Canada, and we anticipated needing to go worldwide in order to enroll it. The reason why we were able to do it is because clinicians, when they started using this drug in clinical trials, realized its potential. We now have hard data that says that, in fact, the clinical community appreciates this profile. They're looking for patients who should be on this drug. They're getting those patients enrolled into our trial. That gives us a lot of confidence moving forward. Okay, terrific. Switch to STAR-0310, the OX40 antagonist, and this is a very attractive target in atopic dermatitis and also clinically validated by pharma's trial. First, maybe you could walk through what is the molecular design and make it a differentiator from other OX40 agents. So, OX40 is increasingly exciting, and as we see more clinical data with OX40 in atopic dermatitis, and very soon we'll see efficacy with the this mechanism in other diseases as well. The clinical community is revving up with excitement about this particular mechanism as a disease-modifying mechanism. It would be the first non-immune suppressive, disease-modifying mechanism for T-cell-mediated diseases anywhere. And that means, that means quite a bit, to clinical community, to patients themselves. And we have what we think could be a potential best in class, for an OX40 receptor antagonist. What we have with 310 is a highly potent molecule that has high affinity against the OX40 receptor, with low rate of antibody-dependent cellular cytotoxicity, which we think will translate to a strong safety profile, and we now know that we have a long half-life. The long half-life means infrequent administration in the maintenance phase. The potency and the affinity mean that we hit the target and only the target, and that we have the potential to drive efficacy to a significant, clinically meaningful degree, with the potential to long-term disease modify and reset the immune system and have positive impacts on patients who have these kinds of diseases. Okay, terrific. You recently presented a preclinical data. I would like to share the data details and also key takeaway. Yeah. Awesome. So, we had been expecting that we wouldn't be able to share preclinical details until the second half of the year. We accelerated that timeline. We showed at the Society for Investigative Dermatology, and then at the European Academy meeting last weekend, preclinical data with the 310 molecule, our OX40 antagonist. And what those data show is that we are highly focused on. We have high affinity to the OX40 receptor, affinity in a single-digit nanomolar range, to the OX40 receptor. In vitro, looking at cytokine release assays, we have potency that is approximately the same as rocatinlimab, which is another OX40 receptor antagonist, which is in phase III. We have a half-life that's about 2-3 times longer than what you'd expect from a normal IgG. So our half-life in monkeys is 26 days. You'd anticipate the half-life typically being around 10 days, so we're significantly longer than that. And we could say with confidence now, based on the half-life, based on the potency and this affinity, that we have the potential for a best-in-class OX40 receptor antagonist. Okay, terrific. When do you plan to start phase one? Right. Go ahead. Oh, so we're in IND-enabling activities now. Expect to file the IND before year-end and start the phase 1a soon thereafter. Right now, public guidance is Q1 of 2025. Okay. It's still early, but would you like to share the thoughts on the clinical development plan, given that other OX40 in the clinical development and also we have several commercial drugs? So how do you think about the suitable patient population? Right. So our strategy is to get first in human healthy volunteer data by Q3 of 2025. Those data we aim to establish proof of concept of a long-acting OX40 receptor antagonist and to provide us dose ranging information for a dose selection information for a dose ranging multiple ascending dose patient study. That would be a phase 1b trial. We anticipate that being in patients with atopic dermatitis. Then based on those data, we will seek two paths potentially. One is straight, fast as possible into pivotal trials for atopic dermatitis. The second is simultaneously, not instead of, but simultaneously seek efficacy data in other indications. Mm-hmm. I mentioned earlier that we expect to start to see efficacy data from other indications with this mechanism. Based on those data, which should establish the validity of this mechanism in those diseases, we could start to look at OX, our OX40 receptor antagonist in those diseases to further expand the potential value proposition of 310 in patients. You're right, this is competitive. One ultimate aspect that will differentiate our program is the ability to deliver against expectations. We've established our company's ability to deliver against expectations with the 215 program, and my intent is to continue that momentum as we get into 310. Great. Then looking into the pipeline, you have two leading programs, each actually for a sizable market. Do you have a plan to amplify the clinical assets in near term? Our intention is to continue to do what we're doing to deliver on STAR-0215, deliver on STAR-0310, and to build the pipeline in the company on the success of those two programs, for sure. Okay, maybe we can revisit what are the key data events and the milestones in the next 12 months? Yeah, great. Yes, so for STAR-0215, number of milestones coming up. So later this year, in the second half, we will report the full data set for those 16 patients in the ALPHA-STAR phase 1b/2 trial. Middle of next year, we will report data from our ALPHA-SOLAR trial, which is a long-term, open-label trial, and at that point, we'll have patients who we have data 12-18 months on Q3-month dosing and Q6-month dosing. So that'll be middle of next year. As Chris mentioned, we will start our pivotal phase III trial for STAR-0215 in Q1 of 2025, and of course, doing everything we can to pull that timeline into this year. That trial, the pivotal phase III, is expected to read out by the end of 2026. For the STAR-0310 program, it's going to be an exciting year as well. We'll continue to present differentiation data for this program at upcoming scientific conferences. We'll complete our IND activities and file the IND before the end of the year and initiate that first in-human trial early next year and expect that readout in Q3. And then, as Chris mentioned, we'll be moving into patients soon thereafter. Looking forward. And maybe lastly, balance sheet and the cash runway and, resource allocate across the programs. Yeah. So, currently, cash runway to mid-2027, so we're in a strong cash position that can fund really important activities on both the STAR-0215 program and STAR-0310 programs, over the next couple of years. And your last question, Actually, you co- Uh, perfect. Finished all. Yes. Perfect. Thank you. And we will wrap up our session here, and thanks for a great discussion, and thanks for joining us, everyone.