Good afternoon, everyone, and thank you for joining us at the H.C. Wainwright Global Investment Conference. My name is Emily Bodnar, and I'm an equity research analyst at H.C. Wainwright. I'm pleased to introduce Mina Kim, who's the Chief Executive Officer, and Gil Labrucherie, who's the Chief Financial and Business Officer of Acelyrin. We'll be doing a fireside chat today. So maybe to start, for those of you who are less familiar with the Acelyrin story, and given you've had some internal changes lately, maybe we could start by walking through your current pipeline programs and where you are in terms of development. Yeah. Okay, sure. So maybe I'll kick off. And maybe I'll go back to earlier this year, when we read out a positive trial in PsA, and also announced at that time early POC data in lonigutamab, which is our program in thyroid eye disease. And, you know, since that time, I've taken over the CEO role in May, and in May, we said, you know, we expect to read out data from a phase III trial in HS in the third quarter, which was a pull forward from previous guidance, where we had guided to end of the year. And we said, "Look, you know, we're gonna look at that data, and then we're gonna make some decisions about sort of the go-forward strategy and pipeline for the, for the company." We announced that data from HS very recently in August, a few weeks ago, and we did make some decisions. We announced at that time that notwithstanding the fact that the data was positive and we liked the data, that we would not be continuing internal development of HS or PsA going forward, right? That was largely driven by the fact that we continued to see data from our program in thyroid eye disease and are really excited about lonigutamab and the path forward there. And also, you know, some considerations about, you know, how best to position HS and PsA, which are very large indications, capital-intensive. And we said that, you know, we think that those programs could be best served by a larger partner, right? With, you know, infrastructure and existing capabilities in those kinds of indications. We also restructured the company in line with those prioritization decisions, and the totality of those actions enabled us to extend our cash runway by about 18 months into mid-2027. That's important because what we also announced around the lonigutamab program was that we're gonna be meeting with the FDA later this year, that we expected to start the phase III program in the first quarter of next year, and that we would be coming back to the market with an update on all of that, sort of a program update, either later this year or early next. But what that means is that that cash runway means our phase III program in TED is fully funded, which we think is really important, with additional runway sort of behind that. And so it significantly derisks sort of that pipeline going forward in that program. The last thing I would say is the IL-17 program, izokibep. We do have a trial in uveitis, which has been ongoing. It fully enrolled earlier this year in the spring, right? So that trial is nearly complete. And we did say we are going to read out data in uveitis. We expect to have that in by the end of the year, right? And like we did for HS and for PsA, that we're gonna look at that data and then make a decision about the go-forward path for that program. Great. Maybe we'll keep the most of the discussion on lonigutamab- Yeah. ... since that's kind of your key focus now. So maybe walk us through the thyroid eye disease landscape, and we have Tepezza on the market, which has a similar mechanism of action to loni. So how do the two differ from each other? Yeah, maybe I'll weigh in here, Emily. I think kind of the way we see the thyroid eye disease market landscape being right now, we have Tepezza, which is the only available biological therapy. It's been a very important treatment option for patients, and we think the IGF-1R mechanism, which Tepezza is based on, is going to continue to be the go-to mechanism in TED due to its central role in dealing with the symptomatology of TED, the proptosis and the CAS response. So, we definitely like lonigutamab as a version, and we can talk about what's really unique about lonigutamab, but from a landscape perspective, we see that. And the next thing that's highly relevant to lonigutamab, because we started as a subQ solution in TED, is that we do see the market migrating almost exclusively to a subQ solution when available. So it's more convenient for patients at home administration, and I think that there's kind of two segments of populations in thyroid eye disease. There's the acute population, where you see most of the prescribing happening today. That's the oculoplastic surgeons, and then there's a large inactive population that 30%-50% develop symptomology that puts them in that active population, and we think with a subQ format that delivers on efficacy, lower exposure like lonigutamab, there'll be the potential to expand the market from this active into the inactive population. Then maybe lastly, I would say that there are, you know, there are other mechanisms that are being studied in the TED space. You know, we think those also could be an important treatment options for patients, probably more likely to sit in the second line, given they're more pan-immune suppressors. So maybe taking a step back, so for those who are less familiar, Tepezza's a fixed dosing regimen, and some of the other therapies that are in development are also fixed dosing regimens... whereas you've kind of alluded to developing lonigutamab with chronic dosing. So maybe just discuss what the unmet need is for chronic dosing, and y ou know, what percentage of patients require additional treatment? Yeah, that's a really good question. The, you're right, the Tepezza is dosed on a fixed-dose regimen of eight doses, and that was really more a result of it being ported over from oncology. It was originally studied in oncology into thyroid eye disease, so there was not dose ranging done within thyroid eye disease patients before it was brought to market. So, there is the potential that, you know, if there were overexposure to that. Like, one of the things that we're really benefiting from in our program, in our phase II dose ranging, is making sure we can dial in the dose to exactly, you know, what achieves efficacy without overdosing and staying within the safety threshold. We think there's an opportunity to see both with lonigutamab early efficacy because it's much more potent, 70 times more potent than Tepezza, and several-fold more potent than the Viridian molecule, that we'll be able to see that efficacy very early. But also the potential to dose, not just on a fixed-dose regimen, but also to explore potential chronic dosing that could drive depth and durability for patients that are not seen with the current fixed-dosing regimens. Okay. And in terms of safety, which has kind of been a big topic here because of hearing impacts noted with Tepezza, is that something that you've seen in your clinical trials with lonigutamab, and how do you kind of think about potential differentiation in the safety front? Yeah. Maybe I can start there. I mean, I think it is an important consideration. I would say, look, our phase II trial that we think is very important, you know, and we're using for dose confirmation, to Gil's point, right? To really calibrate a dose that we think delivers efficacy but maintains the ability over time to prove out, you know, potential advantage on safety is a very, you know, important consideration for us in terms of the development plan design, right? That said, you know, that's something that's gonna play out over time for sure, and, you know, we want to explore that. We'll see that in the phase III, and including in the chronic population, right, that Gil was talking about, and that's where the dose we think is really important. We think, you know, you want to get to a certain Cmin level to drive efficacy, but you stay below, right? That's a hypothesis that we need to prove out, but stay below a certain Cmax level to enable longer-term dosing and potential safety, you know, advantage over time. So the phase I, phase II study that you have ongoing, you've already reported some initial proof-of-concept data, where you've kind of shown at least comparable efficacy results to Tepezza. Now you've announced that you're dose escalating to 50 mg and 70 mg doses. So how do you kind of think about the potential efficacy with these higher doses, and what are you hoping to see? Yeah. Yeah, a good question. The first thing to think about, just taking a step back, just the design of the phase II trial is it's not ascending dose. We're essentially looking at different exposure levels by level of dose and also by regimen. So we've looked at bi-weekly, three times a week, and we're looking at monthly in these cohorts. And really what we're trying to do is exactly what Mina just described, which is we know the Cmin level, where we can get efficacy, and we're trying to dial it in so we have the lowest Cmax on the dose possible with maintaining that Cmin to drive the efficacy. So we want to have, you know, fast efficacy, durable efficacy, and within as narrow a window as possible so we can preserve this potential for a safety advantage on ototoxicity. And also other fronts too, there's the unique binding mechanism with lonigutamab, where it allosterically binds. It's not a competitive binder, and as a result, some of the hyperglycemia that's seen with other treatments, we think we could also have a differential advantage there. So we'll see how that proves out over time. Okay. You've noted that you're planning to meet with the FDA later this year, with the end of the phase II results, and you're kind of preparing to go into phase III next year, so how many patients worth of data are you expecting to have by that time point? And do you believe that would be sufficient to kind of get the approval from the FDA on phase III design? Yeah. Maybe just to step back a little bit in terms of the development plan overall, so we had previously guided to doing sort of this phase I-II, and then doing a phase II- B that we would start at the end of this year. We have since said we're going to complete the dose ranging work inside the phase II, and that's why one of the reasons that we added an additional cohort, so across those four cohorts, you know, it's approximately 30 patients worth of data. Still small n's for sure, and certainly within each individual dose, but a very significant patient population in the context of a TED trial, actually, and even if you think about the size of a potential pivotal trial. What that enables, though, is that we can go to the FDA. We feel, you know, good about going to the FDA to have that end-of-phase II discussion, right? Get buy-in, especially around the size of the trials, right, and what's the required safety database, where again, because we have Tepezza and Viridian's out there too, we don't expect to look, you know, different. But we certainly want alignment with the agency around size, in particular, to enable that phase I trial to start in the first quarter. And the nice thing about not running the II-B is that you can then run both phase III trials concurrently as opposed to sequentially, which is what would've been required had we done the IIB. So it's a little bit of a go slow to go fast approach on the development side. Mm-hmm. Maybe for those who are a bit less familiar, maybe just highlight what the precedent has been like for phase III studies with Horizon molecule and Viridian molecule. Yeah, you're looking at... there have been different approaches here, so there's both the active and inactive population. So you're looking at trials in the 100 to 150 size for a replicate trial, so that's been the precedent, and you know, we want confirmation. I think safety's the biggest driver here because there's such outsized efficacy, that you're really sizing the trials for the safety database. So we wouldn't expect anything unusual. Mm-hmm. Is there any sort of specific patient population that you're considering or, anything that might be different from kind of these precedent studies? You know, we talked about the chronic population, and we're really thinking about where's the unmet need, right, in this patient population, and especially over time, how is that gonna evolve? We know we're gonna have to win in that active population, right, and like I said, you know, we're in terms of thinking about the development program, efficacy is certainly, you know, top of mind, and then, you know, can you maintain sort of safety over time, right, but there are patients where there is high unmet need. You know, the chronic population, we know for some patients they get better on Tepezza, and they relapse and need re-treatment, right? There are patients with age-appropriate hearing loss, or, you know, hearing change is very common in this population. Is there a way to address a broader population, and, you know, go where the unmet need is? So certainly those are things that we're considering as we think about the development plan. Yep, that makes sense. You've announced that you're planning to have an investor day, either later this year, early 2025, with additional data from the phase II study. So maybe just walk us through some expectations for that and what we should be looking out for. Yeah. So we'd really like to come with sort of a more complete overview of the program, right? Which includes the additional data from the phase II trial, right? And this will be post FDA interaction, so, you know, confirmation around what does the phase III trial look like, you know, size, and sort of design, and come with a more complete kind of story around lonigutamab at that time. Okay. You've kind of mentioned this a bit already with the active and chronic type populations, but how do you kind of think about the market opportunity as a whole in terms of remaining unmet need, and, patients kind of failing Tepezza potentially? Yeah. Yeah, I think there's a couple of very important unmet needs that are out there. As you mentioned, there's certainly the durability around Tepezza. There's definitely a relapse population, and that very well could come back to some of the fixed dosing regimen, and that's something that, as Mina mentioned, we want to start exploring for durability and depth. And I think right now the primary prescribing of Tepezza is by oculoplastic surgeons, and as an alternative to surgery. And you know, a substantial, probably five times the population sits in this inactive version, who are 30%-50% will progress into active. So the ability to have an intervention that's earlier in the treatment paradigm for patients could really deliver significant patient benefits, and that's a, you know, very underserved population at this point as patients go on their journey through thyroid eye disease. An earlier intervention could be, you know, very important both for the patients and also a significant expansion of the market. How much of a burden is it for these physicians and patients to undergo IV dosing with Tepezza, and I guess how much of a benefit do you think having a subcutaneous option? Yeah, no, I think it's the subcutaneous option could clearly make the medicine much more accessible. So we were talking about, you know, and for Tepezza, an infusion of anywhere from two to four hours, and the disruption of that during a workday is, you know, a very significant hurdle for patients. So, the ability to have a, you know, a subQ auto-injector, self-administered, at-home solution, you know, can make all the difference in the world, and particularly as you move out of that most acute setting, into that inactive population, even more important to not have the burden of IV administration. Yeah, 'cause it, at this point, it's really an alternative to surgery- Yeah. ... right? And so there's a high patient burden associated with those infusions. Makes sense. Maybe with our last few minutes, touching on the uveitis study that you mentioned in the beginning, maybe just walk us through the design of that study and how that relates to the adalimumab study, and kind of your expectations for, I guess, what you'd want to see to potentially move that program forward. Yeah, and maybe I can just frame it up a little bit, and then I'll turn it over to Gil on some of the numbers. But you know, maybe just to step back, so we started uveitis when we were also running HS and PsA, and it was really kind of the third indication, right? Much smaller, high unmet need, orphan, but a very different kind of proposition as a program, as a development program, when it's decoupled from those indications, right? Which would have been the lead indications, and given the size of you know, PsA and HS, is indications very different pricing. Right, so I think when we think about it as a standalone, maybe just to frame it up, we're really thinking about it now as potentially an orphan indication, high unmet need, right? So very different pricing profile. Yeah. Yeah. When we look at the, as Mina said, when, in, in the orphan pricing framework, when you look at the size of the non-infectious non-anterior uveitis market, and that's, that's where our trial is, that we're describing, is playing. There's about 70,000 patients in the United States, and there's very limited treatment options. There's only steroids, and adalimumab or Humira, as the only approved biologic, in the indication. So huge, huge unmet need, particularly for severe patients. We know that, adalimumab has a fairly high relapse rate, so, you know, 50% - 60% of the patients who start on Humira will, will relapse and need another treatment option. So we think izokibep could play an important role there, as well as an important role potentially up in the, up in the first line, too. We're talking, without getting too specific, we're talking thousands of patients, you know, available who would need a treatment option like a biologic, and against orphan pricing to be, you know, a very significant commercial opportunity, as well as delivering the benefit to patients. So the adalimumab study is fairly similarly designed to your study. Right.. ... in terms of the primary endpoint, so, maybe just highlight what we've seen with adalimumab so far, and kind of just set the- Yeah. ... the benchmark. Yeah, so the trial is designed in a very similar way. So patients start on steroids, right? And there is a forced steroid taper. So we have very much used the Humira trial as a precedent, and then you're looking for time to treatment failure, which is the same design that Humira used. Yeah. Okay, great. I think we're at time now. So thank you very much, Mina and Gil, and thanks everyone for listening in. Thanks. Great. Great. Thank you.