Great. Thank you, Charles, really for making this easy for us. And welcome everybody to our second presentation of the first day of our healthcare conference on our track. We've got Jill Milne, the CEO of Astria Therapeutics. We've known Jill and her team for many, many years. In, you know, Wall Street, you can even call it eons. And it's been a real pleasure in seeing the company develop sort of their product in HAE, the first product, and other products that they're following in other areas. So maybe, Jill, if you could start off with a three to five-minute synopsis of the state of affairs there, and then we can launch into our fireside chat. Great. Yeah, sure will, Hartaj, and thank you for including us in the conference. So, I'll start then with some background on Astria. So our focus at Astria is to develop first choice therapeutics that improve the health and outcomes of patients with allergic and immunological diseases. And first choice to us means that patients and physicians would choose our products because of their strong competitive efficacy, low treatment burden, and favorable safety and tolerability profile. Our initial pipeline is focused on well-established mechanisms, and by that I mean mechanisms that are clinically validated, where we believe we can advance ultimately a best-in-class program. And very much in line with this strategy is the STAR-0215 program. We think that STAR-0215 is well positioned to be the first choice preventative treatment to help normalize the lives of patients living with HAE, a rare, life-changing, and at times, life-threatening disease. STAR-0310 is also aligned with this strategy, and we plan to develop it as a potential best-in-class therapeutic for atopic dermatitis and potentially other indications. Now, back to STAR-0215. So our STAR-0215 is our lead program. It's a monoclonal antibody inhibitor of plasma kallikrein that we're developing to treat patients living with hereditary angioedema, or HAE. Plasma kallikrein is a clinically and commercially validated target for the treatment of this disease. Results from our phase Ia clinical trial support early proof of concept for STAR-0215's target profile, and that is as an long-acting prophylactic therapy, best-in-class PK profile, and the potential to be dosed once every three and six months. We anticipate initial proof of concept results from our Phase Ib/II trial, which we call our ALPHA- STAR clinical trial in HAE patients this quarter, so an exciting quarter for the STAR-0215 program. The second program that I mentioned, STAR-0310, we see it as a potential best-in-class OX40 program that we're developing for atopic dermatitis initially, and we see great potential in other T cell-mediated diseases. We're set up very well for 2024 with STAR-0310 as well. We anticipate filing an IND by year end with this program and advancing into the clinic soon thereafter. We've got a current cash runway into 2027, and that's based on our current operating plan for both of those programs, and so, exciting times ahead, we hope for Astria. Yeah, Jill. I mean, it's fascinating, you know, the time we've have gotten to know each other, you know, for me, the team, and, and seeing this sort of, iteration and the products you've picked. You know, I've kind of heard you talk for the first time about being, you know, developing first choice products. Now, before we go into STAR-0215, which everybody I, I, I know is interested in it, but maybe just talk about this because I think it'll also, we'll circle back to STAR-03 10 and how you chose that. But if you could just delve into this first choice, you know, developing first choice therapeutics also, I think that's actually pretty fascinating. Yeah. So first choice for us, very important for everything we do and how we pick programs and how we're gonna build our pipeline going forward. We want patients, we want physicians to choose our products first because they've got a strong efficacy profile, they have low treatment burden, and good safety and tolerability. Really, we want to develop products that make a true and meaningful difference to patients and really help normalize their lives, and so that's what we mean by first choice. And so we use that as, you know, one of our guiding stars as we think about programs for the pipeline. No, that helps a lot because, you're right. I mean, in an increasingly crowded space, a lot of therapeutic spaces are now actually very, very crowded. That can actually really help, with the kind of therapies you want to develop, right? If you want it to be first choice, just creates a higher bar. Now, maybe that just leads us to STAR-0215. You know, you've talked about, you're targeting plasma kallikrein. This is a pretty, you know, some people would say, you know, very, very, competitive space. Can you just give us a brief overview of the difference between treatment, you know, prophy, the treatment market, the prophy market, and then where does two and five fit? You know, assuming the proof, data, proof concept data is good. Yeah, so, you know, the treatment guidelines for HAE are that it's recommended that all patients be on a preventative therapy, so part of the prophylactic market. And so that's something that, you know, is critically important to help normalize the lives of people living with this disease. So we think STAR-0215, and based on the target product profile that we envision for this program, and certainly supported by the clinical data we've generated to date, we think STAR-0215 really has the potential to be that first-choice preventative therapy in this market. In the United States, that preventative market is about, there are about 60%-70% of patients are on a preventative therapy. We see that growing, and we hope to be part of that growth by providing an agent that has low treatment burden, but highly competitive efficacy and a great safety and tolerability profile. So we hope that preventative segment of the market continues to grow, and not only in the U.S.. And certainly there's a lot of work to be done outside of the U.S.. In Europe, the numbers are, you know, in the 40%-60% range for patients on preventative therapies, and so we think there's a lot of room for improving and normalizing lives of people in those markets as well with preventative therapies that bring what we think we can bring with STAR-0215. Yeah. And Jill, before diving, you know, into the data that you should have coming up and just expectations around that, one of the interesting things, you know, when there was SOLIRIS and ULTOMIRIS, the, you know, the Alexion short-acting and, you know, long-acting PNH and SOF therapies, was that when ULTOMIRIS was launched, you know, once every two months, plus the uptick in Europe was actually surprisingly much more robust than the United States. I know HAE, you know, the European market is still fairly puny compared to the U.S. market. Do you think that if you have a real viable product given once every three or six months with good attack reduction, then ex-U.S. markets really become viable for you? We believe so, and we hope so, and we think this, you know, our product has the potential to make a real difference for these patients. And so certainly that's something that we have our eyes set on. Yeah. No, fantastic. So maybe we can just talk about the three and six -month dosing readouts. Can you just kinda lay it out for us, you know, what are your expectations in terms of, you know, the trial, how it's running, and then what, what should we expect to see when the data comes out in the next few weeks? Yeah. So, so just to set the stage, so yes, our Phase Ib/II trial with STAR-0215, which we call the ALPHA-STAR trial, is a proof-of-concept trial in HAE patients. And so we expect the data that we'll release later this quarter will inform on both the three and six-month dosing regimens. And the data is expected to include efficacy in terms of attack rate reduction, safety tolerability, and also PK and PD. And it will include patients who have received both single and multiple doses of STAR-0215, and it will include data from all three cohorts of the ALPHA-STAR trial. Got it. No, that's great. And then, you know, I guess that once we have the data, you'll go ahead and talk to the FDA, assuming the data, you know, meets or exceeds, you know, the company's expectations. What are sort of the next steps from that? And then where, when could a pivotal start? Yeah, so absolutely. So when we have the data from the ALPHA-STAR trial, our expectation would be we would begin to define our strategy for moving into Phase III, get in front of regulators around the world to finalize the plan for Phase III, with a goal of initiating that pivotal Phase III in early 2025. And of course, as you hear from many companies, we're doing everything in our power to, you know, accelerate that initiation of a Phase III as much as possible. Yep. And then, you know, I guess the lanadelumab is kinda like the bar, right? Is that what we should hope to see in terms of attack reduction, or maybe not? Has the patient population changed? How to think about what would be the bar for attack reduction in the proof-of-concept trial? Yeah, so I think what you're asking is, you know, what does a win look like for us in the ALPHA-STAR trial? So, a win for us in this trial would be an attack rate reduction that would give us confidence for a Phase III success. And, you know, specifically, for the readout, a win would be to see an 80%-90% attack rate reduction with rapid, and also durable effects. You know, I think in this small sample size, in our Phase Ib/II ALPHA-STAR trial, we're looking for good evidence that we're in the ballpark of where lanadelumab is, and. You know, all that together would be a win for us. Yep. Got it. And then, you know, I know that in your previous call and our conversations, you had said that the pivotal could start, you know, maybe early next year. You've got to talk to the FDA, get all the worldwide regulators aligned, et c.. Could there be things you could do to maybe speed that up? You know, or do you think that there's just a series of events that need to happen before you can start the Phase III, and that would occur most likely early next year? So we've certainly put our stake in the ground of early next year, but we are actively looking for ways to speed that timeline up. And, you know, certainly, as you said, you know, one of the most important things we'll need to do, assuming the data from this, the ALPHA-STAR trial is positive, is to get in front of regulators to align on what the Phase III design is, and so, you know, we'll be looking for ways to optimize those steps. Yep. No, that, that's, y ou know, sometimes having really good data and executing a trial very quickly almost works against you once in a while. Because I remember, if I'm not mistaken, Jill, originally, your Phase Ib/II was supposed to read out in the middle part of the year, right? Not in the first quarter. That is correct. So we had an interim analysis designed, and we were tracking to mid-2024 when the trial was started. And through the first many months of the trial, that interim analysis is triggered by enrollment, right? And I have to say we were quite pleased with the rate of enrollment in ALPHA-STAR, and it allowed us to hit that enrollment trigger for that interim analysis. And so we're pleased to be able to move up this initial data to Q1. Yep. We had done a survey on STAR-0215, you know, on its early profile last year, and I think almost every physician was really fascinated, and what they were just waiting to see was the attack reduction data. So lanadelumab was cited as the comp. You know, how's your ALPHA-SOLAR long-term trial recruitment going? Yeah, enrollment in the ALPHA-SOLAR trial is going well. So as you know, ALPHA-SOLAR is the long-term open-label trial, so patients who are eligible from our ALPHA-STAR trial are eligible to enroll in that ALPHA-SOLAR once they've completed ALPHA-STAR. And so we currently have patients rolling into ALPHA-SOLAR from the ALPHA-STAR trial, and we've got data accruing in participants who've received now multiple doses of STAR-0215. And, you know, we'll continue to have ALPHA-SOLAR available for patients as they complete ALPHA-STAR. You know, I think quite frankly, it's a great thing for, you know, certainly for the program, but, we hope for patients as well, to give them the opportunity to continue to receive STAR-0215. Great. Thank you, Jill. I think somebody just online had mentioned that there is some terrible background noise. Jill, it might not be coming from you, it might be coming from me, so I'll just keep on muting myself after I ask a question. Great. And then, you know, ALPHA-SOLAR, Jill, what will a potential Phase III look like? I mean, again, is lanadelumab Phase III a comp there, or are any ways to kinda, like, speed that along, assuming, you know, you get a win in the Phase Ib/II? Yeah, so we're actively working on our design of the Phase III, and we'll certainly share more information on that Phase III, you know, once we have the data from ALPHA-STAR and once we have some regulatory feedback as well. You know, certainly this is, HAE is an area where there is a well, you know, defined regulatory, clinical path for, pivotal Phase IIIs, and, you know, you can expect some elements to be similar to what we've seen with lanadelumab and, and some of the other recent Phase III trials that have, been run. The last question here, Jill, which is that you've presented, you know, the company has presented some pretty fascinating data on market research, looking at payers and physicians. Can you just maybe just synopsize that for us a little bit? You know, three-month and six-month. You know, especially talking to patients, how much conversion can you see on patients, you know, with a three-month and a six-month profile, and what do physicians and payers think of it? Yeah, we've, as you said, we've done some pretty extensive market research with both patients and physicians. And you know, what we have found is there is great interest in both a Q3-month dosing regimen and a Q6-month dosing regimen. And I think both patients and physicians see those profiles as being you know, substantially different, better than what's available to them today and what we see you know, coming along as well. You know, very different from a Q2 week, very different from a Q1 month. And so it gives us confidence and encouragement that we're doing the right thing with STAR-0215 by advancing a Q3-month and a Q6-month dosing regimen. And then last question about STAR-0215, Jill, which is that, you know, now we've got orals, we've got antibodies, you know, in the prophylactic area. There's also looks like gene editing potentially in the future. How do you see that playing out relative to STAR-0215? Yeah, we, you know, you know, I don't think we would wanna trade places with anyone. I think STAR-0215 really has the potential to be the first choice preventative therapy in HAE. You know, I, I do think with a low treatment burden, like what we think we can support with STAR-0215, it, you know, has the potential to really take market share from different segments of the market, whether it be oral or the other injectables. I think for gene editing, gene therapy approaches in this disease, I'm not sure it's the best match, HAE and, gene editing or gene therapy. I don't know yet if the risk-benefit is there when you have, you know, trusted modalities in the form of a monoclonal antibody that can provide robust efficacy, and good, you know, proportion of patients attack-free, whether that risk-benefit is truly there. Yeah. No, no, it, I think that makes a lot of sense. You know, the treatment burden is interesting because you've companies as diverse as in HIV, where, you know, Gilead is trying to go to a, you know, lower treatment burden, extend out, you know, the duration of treatment, et c.. We talked about PNH with SOLIRIS and ULTOMIRIS, so, you know, it seems Astria is already going to places that large companies have figured out, you know, there's a high unmet need. Anything else about STAR-0215, Jill, that we haven't touched on before we talk about STAR-0310, that you think is important? I think we've covered it pretty well. Yeah, we're very excited about this readout this quarter, and look forward, you know, if positive data from ALPHA-STAR moving as quickly as we can to a pivotal. Yeah, fantastic. And then maybe, Jill, you can, I know, well, you did a conference call last year with STAR-0310 and the asset you had on in-license. Can you just give us a synopsis about STAR-0310, and what really intrigued you about this asset? Yeah, for sure. We, we became very interested in the OX40 mechanism because of its, broad potential in a number of T cell-mediated diseases. And, you know, STAR-0310 in this program, we saw fit very well with our strategy for how we wanna build our, our pipeline. We, we think that STAR-0310 has the potential to be a best-in-class and a first choice in atopic dermatitis. So just for background, STAR-0310 is, a monoclonal antibody that is an OX40 receptor antagonist. And as such, has the potential to, target multiple effector T cell pathways. It, really with this approach, we aim to target a broad set of, T cell populations that are known to contribute to, diseases like atopic dermatitis. We hope that translates to the potential to have higher rates of clinical response in more patients than what's currently available with the current biologics. And we also believe that the OX40 mechanism could be disease-modifying and truly change the course of the disease here. And so that's something, you know, we'll certainly be looking at as the program advances. And so, STAR-0310, it was designed for high affinity and high potency for T cells. And we believe with that profile, can match or potentially beat the efficacy seen with some of the other OX40 programs. The half-life of STAR-0310 is extended with the YTE technology. And the goal there is to reduce the time between doses. And, you know, we're obviously, you know, trying to advance STAR-0310 for the ability to be delivered subcutaneously. You know, all signals point in the right direction there. Also, STAR-0310 is designed to be T cell preserving with low ADCC, and we think that could be, provided the potential to be a best-in-class among the OX40 receptor antagonists from a safety profile perspective. So we're on track to submit an IND later this year, and we'll look to advance into the clinic soon thereafter. Yep. No, that's fantastic, Jill. And I'll just note to the audience that we've done an audio test, and it seems our streams are fine, so you might wanna just check your own connection. There might be a problem with that. And again, if anybody's got any questions, please feel free forward to type it directly to us or put it on, you know, on the internet page that's available for asking questions. Jill, you know, on STAR-0310, there are already two molecules in development, so I guess we've got a bar, you know, out there. Amgen, I'm forgetting who the second one, I think it's Boehringer Ingelheim, right? Sanofi is one of the other ones, and yep. Yeah, sorry, Sanofi and Amgen. Maybe you can just talk to us that, you know, once you get the IND approved, what, how will you look to move, you know, STAR-0310 along, and what should be the kinda like, you know, the hurdle that we're looking for as you go through early stage trials? Yeah, it's a great question. I mean, it's this is an instance where, you know, not being first in class may help us be best in class. You know, we've certainly benefited from the data that these other programs, the Sanofi amlitelimab, and the Amgen rocatinlimab, have generated, and that's, you know, the information we've learned from those programs are, you know, how we've developed our target profile for STAR-0310, and how we've engineered that antibody. What we'll be looking for in our first-in-human study is some elements that will speak and read on our target product profile. And so we'll be looking from a PK perspective to look for that long duration of potential long duration of action. We'll be looking, you know, from a safety tolerability profile, you know, this low, ADCC. And, importantly, you know, from there, we'll look to go into patients to start to see elements of proof of concept from PD biomarkers, and, you know, from there, efficacy signals in, patients with atopic dermatitis. And, and again, we think STAR-0 310 has the potential to be a best-in-class among the OX40s, and we'll be learning continually, continuing to learn from these other programs, as well as our own, throughout this year and into next. No, that's great, Jill. And, you know, I guess, you know, in terms of your cash runway, you know, you've gotten a lot of support from current and your investors. Can you just talk a little bit, first and foremost, about how your research and development, you know, that line item looks like going forward? You've got a lot going on. And then secondly, how to think about your cash runway as, you know, potentially bring more products into your portfolio. Yeah. So right now, our publicly stated cash position is into mid-2027, and that's based on the current operating plan. And so in 2024, we do expect expenses to be noticeably higher than they were in 2023. And that increase is due to STAR-0310, the IND-enabling activities and preparations for the Phase I, as well as the full year of the ALPHA-SOLAR long-term open label trial. And so that's different than what, you know, 2023 was. And we're beginning Phase III preparatory activities this year as well. So you'll start to see expenses in 2024 being higher than 2023. Right. That's good, Jill. You know, we're getting to the end. We've got about five minutes left. Had a question online, you know, about, you know, KalVista, it seems, has is having a little bit of a rougher day today. Just any thoughts on their data? You know, is there, i s it just the area is very competitive? You know, are people looking much more carefully at, what, you know, efficacy looks like in these kind of readouts? Just any thoughts there, Jill? Yeah. I, w hen I woke up this morning, I saw the press release, so I haven't had a long time to digest the data. You know, my first high-level pass was, it was, you know, as expected from the Phase II, but certainly we will be looking into that. I mean, it is a competitive space, but eager to see more from that program. Yep. So I guess it's sort of like, you know, when you're getting, you're already, I believe, seven or eight markets, right? You know, products in the market, of which five, I think, are prophylaxis, right? If I'm not mistaken. Then, I guess every company that comes on board, you've got to have something in terms of risk, benefit, tolerability, you know, dosing profile, et c., that's really, quote unquote, "superior", you know, in, in effect, right, in HAE. Right. Right. And yep, absolutely, and KalVista, of course, fits in that on-demand category, where STAR-0215's in the preventative therapy. But you're absolutely right. You have to bring something meaningfully different for patients. And, you know, our goal, normalize... help normalize the lives of people living with this disease, and we think the profile that we've seen so far to date clinically with STAR-0215, gives us, hope that we're going to be able to do that. Yep. And Jill, you know, like for example, when I think about rheumatoid arthritis, I believe methotrexate was oral, right? And then that was sort of the initial area where people get, and then you get on to the injectables, off that, the biologics. You know, could you see HAE becoming like that, which is the orals are for those sort of, you know, earlier stage, you know, less severe patients, and then the injectables are actually the therapy of choice that everybody kind of gets on? Or do you think HAE is unique in some ways? You know, I think HAE is unique and different from a disease like rheumatoid arthritis, and the reason I say that is this is a disease that's driven by pulses and increases in plasma kallikrein activity. So something triggers the plasma kallikrein levels to go up, to cleave high molecular weight kininogen, release bradykinin, to do its thing of inducing these swelling episodes. So this is a disease where you want a drug that keeps plasma kallikrein levels in check all the time. I think that, to me, if I were a patient taking a daily oral, where, you know, I don't know if I'm gonna take it the same time every day, I may go away and miss, you know, forget to bring my meds, and I'm off it for three days. That's not great for a disease where you wanna stay above a certain level to keep that enzyme in check. I see something like STAR-0215 as having really great potential for patients here because you take it four times a year or two times a year, and your levels are kept in check, and you don't have to worry about that day-to-day variability that can come about with a daily oral or, you know, compliance if you forget your meds. So this, to me, is different than RA or a disease, you know, like that, where these are acute episodes that you need to prevent from even starting. Yeah. No, absolutely. You know, we've seen the arguments, the pharmacoeconomic arguments, for example, with SOLIRIS and ULTOMIRIS. Gilead's already starting to present that with their HIV approach for once every, you know, once a week oral or once every six months injectable, where for the patients, their burden is also a lot less in terms of out-of-pocket costs. You know, just what has your research shown there? I mean, it seems like physicians would definitely be interested, but, you know, it seems like the burden to the healthcare system and then to the patient, that would be less also. I mean, is that what you've seen from your, from your marketing research data? Yes, and that's something that we, you know, intend to look deeper into to build the case for that. And, you know, I think you're absolutely right that we see it, if a patient can keep, their plasma levels, plasma kallikrein levels in check, for long durations of time, it's gonna be better for the patient, and it's gonna be better for, the people around the patients and, from a healthcare perspective as well. Yep. Great. Jill, we're at time. Is there anything that, you know, you'd like to mention that we haven't talked about that we should just kinda keep in mind as we're approaching the STAR-0215 readout, for the proof of concept readout? I think we've covered it. We're looking forward to a very exciting 2024, and initial proof of concept results in patients from ALPHA-STAR. Jill, always been a pleasure. Please give our best to the team, and we'll keep the conversation going. That sounds great. Thanks, Hartaj.