All right, thanks everyone for being here and wrapping up the day with Metsera. I'm pleased to have with us Whit Bernard, CEO and co-founder, and Brian Hubbard, Chief Scientific Officer. I guess we'll start off with you giving an overview of the company, some of the key pipeline assets, and the platform, and we'll go from there. Sure, great. First of all, thanks so much for having us, and thanks for all the work you're doing to help kind of get the word out and clarify a lot of what we're doing. I really appreciate the role that you and Wells Fargo play in the community. Thrilled to be here. We're Metsera. I would characterize us as a scale-obsessed company focused on the next generation of innovation in obesity therapy, really around therapeutic peptides targeting nutrient-stimulated hormone pathways. GLP-1 being a very exciting example of one of those pathways, but there are at least a dozen others around it, of which we know how to drug at least five right now, and working on all of those targets. We had the good fortune to bring a couple of very experienced teams, one that I come from at The Medicines Company and one that Brian leads that's been doing translational work for a long time, around a really incredible portfolio of assets developed by Sir Steve Bloom at Imperial College, testing over 10,000 peptides in vivo, focused on potency, durability, and fundamentally scalability and combinability to get to this next generation. What we've kind of yielded from that is a couple of clinical stage assets and a really exciting preclinical pipeline as well. We have an ultra-long-acting GLP-1 receptor agonist, fully biased, MET-097i, rapidly approaching phase III later this year, reading out two of our phase II studies in a couple of weeks. I think some of the exciting distinguishing features of MET-097i, it's the longest, at the time we brought it into the clinic, it was the longest-acting therapeutic peptide in development in any category, and it's been surpassed only by MET-233i, our amylin analog, which beat it by about a day. The peptides that the Zihipp team engineered were incredibly durable. It's also about tenfold more potent than tirzepatide. That lowers the API requirements, improves manufacturability, and as a mono GLP-1, it's fully biased, which clinically we've seen has given it an efficacy and tolerability profile really comparable to the best-performing dual agonists. On tolerability, maybe a bit better because of the half-life and the way we've been able to develop around that. Also, as mentioned, having amylin that's in phase I-B, II-A studies, both as a monotherapy and in combination with MET-097i. MET-233i, our amylin analog, was engineered to be combined with MET-097i, so they're soluble in the same pH range. The eventual drug product here will just be co-formulated in solution, right? Very simple and elegant design. Matched half-life, 18 days for MET-097i, 19 days for MET-233i. That enables monthly dosing as a combination product, which is very unique in the category. Of course, we showed some great, very exciting clinical data on the amylin analog earlier this summer, up to 8.5% placebo-adjusted weight loss with exceptionally well-tolerated starting doses, and the 12-week studies we have ongoing are really about triangulating between those two data points to get to placebo-like tolerability with excellent efficacy out at 12 weeks and kind of seeing where we go from there. Finally, we have an oral strategy, which was a bit of a contrarian bet when we set up the company. We had the belief, and this is a lot of Brian's thinking, that small molecules were going to be fundamentally limited in their ability to get to high levels of weight loss that's well-tolerated, largely because it's just difficult to engineer a small molecule to have a half-life longer than 24- 36 hours. It's absolutely incredible what Lilly and Chugai have done in getting to that point, frankly. Our view was, what if we took a different approach? What if we thought about making oral peptides scalable? This seemed for a long time like an intractable problem, but given the potency we have in our portfolio, we have this huge leg up because you're doing the same amount of work with one-tenth of the drug. We built an oral strategy really grounded in potency. We deliver our peptides to the small intestine. They're very stable, so they're able to be active and absorbed in the small intestine. That eliminates the food and water restrictions that we see with other oral peptides. We'll have clinical data later this year, and we're all focused on basically, can we deliver an injectable-like efficacy profile at a low-dose oral that's scalable? From there, I could talk about some of the ultra-long-acting maintenance and prodrug strategies we're working on, which are preclinical, but I've probably already taken too long. That's kind of where we are from a portfolio perspective. Broad portfolio, moving quickly, incredibly focused on these scalability challenges that we think are going to define the future of this category. And a lot of interesting catalysts coming up in the next nine to 12 months. Starting with MET-097i, we're expecting a couple of phase II readouts in September. Yep. I know you already touched on the bias signaling differentiating this asset. Can you also talk more about just how that long half-life enables great tolerability? Yeah, maybe Brian, you want to take that one? Sure. On bias, because it's related, it's sort of a half-life phenomenon. What bias is, is really when GLP-1 binds to the GLP-1 receptor, two things happen. There's an activity signal, and then there's a signal through something called beta-arrestin that takes the receptor into the cell and degrades it. A biased GLP-1 or a biased ligand only signals through one of those pathways, and in our case, it's through the activity pathway. What that means is over time, there's more GLP-1 receptor that stays on the cell surface and stays active. You're kind of increasing the half-life of the receptor, if you will, on the cell surface. On the peptide side, we have this ultra-long-acting half-life, these observed half-lives of 18 and 19 days. What that allows us to do is when we dose weekly, we're dosing a drug every seven days, but the half-life is much longer than two weeks. What happens is when you give your next dose, you get kind of a slow rise in concentration. You don't get these big dips where you go low and high. In the GLP-1 class and in the amylin class, the GI AEs come from when you go from a low concentration to a high concentration too fast. Because we dose it weekly initially, we don't get those steep lows to highs. Therefore, we can get better tolerability. Also, because it accumulates, in essence, if we give four doses of a dose, it accumulates to really the next dose level. We don't really have a step when we dose, titrate up the next dose. That's why our initial data with dose titration of 0.4 mg to 0.8 mg to 1.2 mg was so well tolerated. It was just a smooth rise in concentration. By having a biased GLP-1, we keep more receptor available. By having an ultra-long half-life, we keep more peptide available, and therefore, we can have this great tolerability, but also prolonged efficacy that we see. We started to see potential for that great tolerability and potential for monthly dosing from the 12-week data that you guys have read out. Can you just help us frame like what you saw and perhaps just put it into context of, you know, the single agonist showing dual agonist-like profile? Yeah, absolutely. The 12-week study, that's a study we started as we were just reminiscing about the design of that study, because the moment we realized we had 13 weeks of tox coverage, we ran that study. It was basically designed to answer a few questions. One, what happens from an efficacy perspective as we get out to steady state? We had 12 weeks of weekly dosing. Two, what happens when we introduce titration? We knew that tolerability without titration was competitive, but to Brian's point, we had this theory that if you introduce titration on top of accumulation, you're going to take a smooth curve and make it even smoother, right? Basically, approximate this kind of slow linear ramp in exposure. Can you take good exposure or good tolerability and make it great with dose escalation? Finally, we had a 13th dose that just made it into the tox window. At week 12, we're at steady state. We've crossed the threshold of where we think we've mostly saturated the physiology, saturated the GLP-1 receptor. What if we take a jump to an exposure match monthly dose? Will that be tolerated? Our theory here, which is different than what others working on monthly products have done, is that you really want to gradually increase exposure to optimize tolerability, and then you can take these bigger jumps that get you to the longer dose interval. Those were the three questions. I think what we were able to show is from an efficacy perspective, we absolutely tracked with dual agonists. We were 10%, 11% placebo-adjusted weight loss at 12 weeks, which is really at the high end of the competitive landscape. The tolerability with titration was exceptional. In that cohort of 20 patients where we titrated 0.4 mg to 0.8 mg to 1.2 mg, we had two cases of vomiting and one case of nausea in the entire cohort over 12 weeks, and we delivered tirzepatide-like weight loss, about 6.3% placebo-adjusted at 12 weeks. Finally, those monthly steps were well tolerated. We had a very modest tolerability signal at a 4x jump. I have to say that was the part of that trial I was most worried about. It was right around when we went public. That data was like two weeks off the press when we took the company public, and we knew intuitively that the mechanistic theory made sense, but nobody had ever tested that kind of a Cmax before, and it was extremely well tolerated. It was fine. Entirely consistent with what Brian had predicted. That really set up what's become VESPER-3, which is an ongoing study where we apply the titration learnings out to week 12, weekly dosing with two titration steps, and then we jump to a 4x exposure match monthly dose. Thankfully, we have the tox coverage to follow multiple monthly doses all the way out to week 28, and we'll have that data later this year. Got it. We'll have interim VESPER-3 data coming up in September, also the full set of VESPER-1 data. That's right. Can you talk about the rationale for the study design, why there is no titration in VESPER-1? Yeah, and this is just all about the speed at which we're moving towards phase III and ultimately towards the market, right? I think when we were looking at phase I data for MET-097i, we saw very early that we had a very competitive compound, right? We were active at very low doses. We had this unprecedented human half-life of, you know, 18 days, and we had, you know, extraordinary efficacy and good tolerability. You know, we said, how quickly can we, you know, if we think right to left, how do we take this starting point, this MAD data, and envision an approved BLA product, and how quickly can we get there? It turned out the best way to do that was to actually take the questions that one would normally answer in a single phase II study and split them into multiple studies. We knew we still needed to run a pilot with monthly dosing. We weren't there yet, right? We said, let's run a weekly study. We knew the most important question we had to answer in phase II was actually a dose selection question, right? Like the classic role of a phase II study is dose range finding, right? We knew that we had good tolerability without titration. We said the most efficient way to pick doses is don't titrate. Look at four doses versus placebo out to 28 weeks. You'll have enough separation at 28 weeks if you don't titrate to be able to pick doses and model out sort of plateau weight loss, which is exactly what we want to bring to FDA later this year. We'll explore titration in the phase II- A study, which is exactly what we did in the 101 study. Once we had the findings around titration and the findings around monthly dosing, we introduced those into a second study called VESPER-3. VESPER-1 was really designed for the sole purpose of picking doses. It enables us to do that faster. It enables us to bring that data to the FDA for phase III initiation later this year. In parallel, we built in this interim analysis to VESPER-3 so that we could be looking at the weekly titration data more or less in parallel and bring that data to the FDA in the same package. What's basically happened is VESPER-3 enrolled quickly enough that we were able to basically dovetail the VESPER-3 data with the final VESPER-1 data and just disclose it all at once. We will be sharing externally exactly the data set that we'll be integrating into a briefing package for the FDA, you know, again with the goal of getting phase III going by the end of the year. That's the thinking there. Just prior to your Q2 update where you set this September data readout timeline, you guys had said a mid-2025 readout. Yes. That's led some people to think, oh, the readout was pushed out. How would you address that? Yeah. Actually, what happened was VESPER-3 came sooner than expected. We held up the VESPER-1 unblinding analysis by a couple of weeks so that it could catch up with VESPER-3. This was actually all about moving faster than expected, not slower than expected. Yes, it trickled into September. I've had lots of debates as to the definition of mid versus late, but I've learned my lesson that enough people think mid ends in August that we'll go with mid in August from now on. It was really VESPER-3. I think VESPER-3 enrolled in about five weeks, so exceptionally fast. Our operations team has been doing a great job with a great group of site partners. That enabled us to bring that interim analysis in so that instead of just tucking it into the FDA documents, we could actually integrate it into the VESPER-1 external release. That's really all it was. Got it. How should we think about the bar for success for VESPER-1 and then tolerability for VESPER-3? Are there any differences in trial design or enrollment to think about as we compare the phase I to phase II data and then comp to phase III trials? Yeah. I'll take the kind of bar and then maybe Brian, you can speak to the enrollment decisions and how all that can change. The target profile we've set for MET-097i is that it should be dual agonist-like from an efficacy perspective. To Brian's point, we believe the reason the dual agonists perform the way they do, particularly tirzepatide, is not because of GIP. We believe it's because of bias. MET-097i, as a fully biased GLP-1, has consistently performed like a dual agonist, albeit substantially more potent to date. From an efficacy perspective, we sort of want to hold ourselves to that bar. What that number is varies widely across trials, but I would expect it to be in excess of 10% placebo-adjusted weight loss at the 28-week mark. I think the tirzepatide mark at 28 weeks is around 13% placebo-adjusted. I'd really love to play this game of name a number, but I think all of us can look at publications and look at competitive data at that time point to see what in range looks like. I think Amgen, for example, with maritide without titration is around 14% placebo-adjusted. Low teens would be a great outcome. From a tolerability perspective, we want to see how well we can do. Thus far, we saw exceptional tolerability in the titrated cohort. I think those numbers were so low that it would be difficult to replicate. Whenever you say you have 5% nausea because it was one participant in 20, that's a high bar to replicate, but we should at minimum be seeing a tirzepatide-like tolerability signal. The thing we'll be interested in is does the half-life itself translate into better tolerability, whether it's against nausea, whether it's against diarrhea, where we've consistently seen lower rates in past trials, or vomiting or other parameters. The tirzepatide bar we think is the right one. I don't know, Brian, any comments on just how performance can change from phase to phase? Obviously, people lose more weight in phase I than phase II and more weight in phase II than phase III. Why is that? Maybe what are your thoughts on? It is definitely true. It's for a couple of reasons, and it's true across the class, and it's something we expect and see as well. In phase I, the type of patient population that you have in is a very different group of individuals. They're phase I, they're shorter trials. Oftentimes, it's people who participate in clinical trials on a regular basis. They also know that they are in an obesity study, and the cohorts tend to be on active, tend to be in an eight to 10 number range. What one observes often is that you get really good weight loss, and in that phase I study, we are also pushing doses very high on purpose, right? We want to test the whole dose range. Everyone else will across all therapeutic areas, you do a full dose range, and in GLP-1s, what that means is from low to really until you can't, you hit the tolerability limit. What that means is you're giving people a lot of a GLP-1, and they don't eat. You get these quite dramatic weight losses you can if you push that dose in phase I. In phase II, you tend to dampen that down a little bit because now you're trying to hone in. You're still dose ranging, right? You're still broad range, but the ends are a little bit narrower in. You're kind of honing in on what's closer to real-world weight loss. Of course, your phase III, you're not pushing the limits anymore. You're trying to make a marketed product. This comes down to what is a, on a weight loss perspective, what's a healthy rate of weight loss, sort of 0.5% per week. In addition, it's getting to the plateau that you want to maximize out the mechanism. In essence, your doses range broader early. You push the limits. You narrow those limits in phase II so that body weight tends to come down a little bit. In phase III, you're looking for that marketed drug, which now you're finding that true number, which tends to be what the mechanism can give you. I would say generally, we're moving towards a more obese population as we get. You should see the baseline BMI come up a little bit from phase I to phase II, which does have some impact on some things we see, again, across trials. You start with a relatively low BMI. You can have kind of skewed weight loss in the early weeks. It generally plateaus, but you don't always see that plateau early. That can distort numbers as well. It's a more kind of label-appropriate population. Yeah. When we look around at other people's trials, what I can say from a Metsera standpoint is our goal is to make a drug. What that means is we challenge ourselves to ask the hard questions of ourselves. We see some trials where it's clearly weighted towards showing more efficacy. We know certain populations can respond better. Females, African Americans can respond in a way to these drugs, especially in shorter trials, greater. We intentionally stay away from that because what we care about is the true answer. If you want to make a drug, it doesn't matter if you gimmick yourself along the way. You're actually missing the right answer. We challenge ourselves often harder than investors, although some days it doesn't seem that way, because we have the end in mind, not some intermediate milestone. Yeah. With the bar being tirzepatide, if you do show that level of efficacy and tolerability, what does that say to you for where MET-097i can fall in the treatment paradigm for obesity? Yeah, I mean, I think we see it as effectively a best-in-class candidate for the large portion of the population that is well served by dual agonists like weight loss. Call it that, you know, mid to high teens% placebo-adjusted weight loss that we've seen kind of consistently. Why is it best-in-class? First of all, we're going to be one of two potentially assets available with monthly dosing. We're going to have that with, I think, extremely competitive tolerability, which is part of our goal. We'll actually have it with, and we don't talk about this that much, but with, you know, at most two titration steps versus four or five. A much simpler, easier to use, more consumer-friendly profile. We think of it fundamentally as, you know, the most consumer-friendly profile in a consumer-driven portion of this market. That's how we would develop and position MET-097i. Straightforward chronic weight management development program in diabetics and non-diabetics to really position it to win share on attributes. All right, so that's what we'll expect in September, late 2025. We're also expecting 12-week data from your amylin. Can you talk about the differentiated profile that you've seen so far, the five-week data shared today, I think back in June? Yeah, we were incredibly excited by the amylin data. As Steve Marso, our Chief Medical Officer, says, sometimes you get data sets that are just so straightforward, they sort of present themselves. This was one of them. You know, we tested a fairly broad range in the SAD. To Brian's point, we compressed that range a little bit in the MAD. We went from 0.15 mg up to 1.2 mg. Already assigned, we had a pretty potent compound on our hands. The highest dose we tested in MAD was 1.2 mg. We knew preclinically, I mean, Brian and Dodd and our toxicology team had a very hard time getting dogs to eat. I hated this compound. I hated this compound. Because, you know, you need to manage the level of weight loss in these toxicology studies. You want to keep it above, you know, you want to keep it at 20% for animal welfare reasons. It was very, very hard to get dogs to eat on this compound. We knew it was going to be potent. What we saw was very, very clear dose response of weight loss up to pretty exceptional levels of efficacy. To the earlier point on more efficacy than you need, 8.4% placebo-adjusted at five weeks. Pretty good signal that we were working with a potent compound. Of course, maybe more importantly for us, competitive efficacy at extremely well-tolerated candidate starting doses. 0.15 mg and 0.3 mg, we had 2.5% placebo-adjusted weight loss over five weeks. Again, that's that kind of magic target we'd look for, a half a percent per week, which is really what you're trying to dial in these titration curves. I think one case of vomiting across both cohorts and a couple of cases of nausea that really mirrored placebo. Where we're headed with this one is can we take that starting point, that placebo-like tolerability, which is something we've really never seen on a GLP-1, and titrate from there to these higher doses like 1.2 mg and get to those higher levels of efficacy without DAEs along the way. I think the opportunity we have with amylin monotherapy, which is one that I certainly didn't fully appreciate until we brought MET-233i into the clinic, because I didn't quite see it in the cagrilintide data, is I think we have an opportunity for GLP-1-like weight loss. We'll see what that means as we get into later trials, is that, you know, low teens, high teens, somewhere in between, with placebo-like tolerability. That would be an incredible advance, and it would create, I think, a pretty important therapeutic alternative for patients who are struggling to tolerate GLP-1. Almost in parallel to the mono data, we were able to get alignment with FDA on initiating combo dosing. One of the most important findings in that MAD data set is you saw we kind of overlaid the PK of MET-097i and MET-233i, and they basically are superimposable. That sets us up very well for combination dosing. The two things you need to be able to combine compounds are compatible pharmacokinetics and solubility in the same pH range. Both of these were engineered for both of those. We're testing a range of cohorts and a range of titration schemes in the combo. We'll have both the mono and the combo data sets available later this year. Okay. For the amylin class, it does seem like people point to Lilly's eloralintide data that also read out around June as kind of like, you know, it's shown really great tolerability at strong efficacy as well. How would you compare the profile that you've seen for MET-233i so far against? Yeah, I think the thing that's most exciting about eloralintide from our perspective is that it has a really long half-life. It's the only non-Metsera peptide we've seen in development that appears to be suitable for monthly dosing, right? They're at about 15, 16 days from dose to 50% Cmax. I think that's a lot of the reason we saw the excellent efficacy and tolerability in that trial, because they're getting the benefit with a half-life that long. You get the benefit of accumulation, right? You're probably accumulating about fourfold over those 12 weeks. There's a third element here, which was really interesting about eloralintide, which was even at starting doses, it delivered dramatic weight loss, and even after you take into account the accumulation, that kind of helps get them there. Tolerability was exceptional in every dose group. Yeah. I think the offset to that is there were other issues in the high dose groups. You saw examples of fatigue, depression that suggest to us that the rate of weight loss was just too high. Frankly, they're going to have to titrate anyway, is our assumption, and you probably end up with a similar profile. I think the big debate around elora and MET-233i at the time, at least, was about the sort of bias towards human amylin analog versus DACRA. Oh yeah. This is a good, juicy, controversial topic since we have Brian on the record. I know Brian, we've done a little bit of work on this. What are your thoughts on DACRA versus human- selective amylin? Right. It's worth just stating that the amylin receptor is the calcitonin receptor with a small peptide bound to it. There are three different versions, one, two, and three, very novelly named. What we've seen is for the peptides that are leading in the class, you know, cagri, petro, Gubra, elora, and 233. If you look at the profiles and you look across all three amylin receptors and the calcitonin receptor, and you look at that in vitro and in vivo, they all engage with the calcitonin receptor at the levels that they're delivering efficacy on the weight loss. We believe that, one, all of them hit all three amylin receptors, but they also clearly at levels of efficacy. Actually, Novo did a really nice poster at the ADA on this, showing this in vivo. We've done analogous work across the class of peptides. We think this whole, is it selective? If not, it's a little bit of a gamesmanship about talking about one amylin receptor and calcitonin versus the whole class. We just think that they're all very similar, which means we all may get there differently, but in the end, those peptides, certainly petrolantide, Gubra, us, and eloralantide, should be able to get to the same level of plateaued weight loss. I do think the class is differentiating, though, more on what Whit was saying, which is it's kind of us and eloralantide with long-acting, which means better tolerability as you dose up versus the more weekly versions. That's where I see the differentiation in amylins. It's more around how they get dosed, how many steps you might have to take in a titration. It's sort of like the us and eloralantide, and then the petrolantide, cagri, Gubra is really the other bucket. Okay. For MET-097i, you already have a drug that looks to be efficacious and has potential to be really tolerable. Where does amylin and combo fit into this strategy? Yeah, it's a great question. Certainly, amylin mono, this is one we debate a lot. I think that it's easy enough to say, well, amylin's a different mechanism and it's really well tolerated and we want lots of alternatives. If we have GLP-1s that are as well tolerated, we have decades of clinical outcomes data on GLP-1s. The idea that we would switch backbones overnight over a modest tolerability scheme was, I think, a bit much. I think if we can see true placebo-like tolerability on amylin, I set a pretty high bar for amylin to be an exciting monotherapy construct. I think if you can really iron out the tolerability and you can dial in the weight loss to the levels you want with escalation, that becomes a really exciting alternative because even on, you know, well-tolerated GLP-1 constructs like MET-097i, you do have some patients who have a tolerability challenge. Is it 10%, 15%, 20% of the population early on, you know, are they going to want an alternative that's different, that's potentially better tolerated? I think amylin monotherapy has a lane there that could be quite interesting, especially as we think about a really broad and addressable population for these drugs over time. I think the combo actually, I mean, this is a very unique lane that I think is incredibly exciting. The really important work that Novo has done with cagri and sema is really just scratching the surface of what we can do with multi-hormone combinations. Our goal with the combo is to be sort of at the top of the category on weight loss. We think combining a very potent biased GLP-1 with a very potent well-tolerated amylin, you know, we do not see an efficacy ceiling until you're getting close to 25%, 30%. I think we really do think the mechanisms are additive. The challenge, of course, with GLP-1 and amylin, as we saw with cagri and sema, is that the GI adverse events are also additive. If you have well-tolerated starting points, you can solve that with dose escalation. We start low, we go slow, we leverage accumulation of the combined PK, and we sort of gradually escalate. When we actually think about the development objective for these 12-week cohorts with the combo, what we're really focused on is can we deliver an appropriate level of weight loss with exceptional tolerability. I think if you can see exceptional tolerability with appropriate levels of weight loss, you know you're in a very different zip code than where we were with the cagri-sema data. I think there were just tolerability challenges with both of the starting points, especially with semaglutide, where you're kind of already at a competitive tolerability ceiling with, you know, 40% nausea, 20% vomiting. We actually kind of view our combo program as a bit of a blank sheet of paper because the raw material is just so different. We're excited to show data later this year on that. Got it. It's probably worth saying that to the best of our knowledge, at least, MET-097i and MET-233i represent the only monthly that could be in this category of weight loss of 25%. Yeah, I mean, I think the only other drug in this category really in development is probably tirzepatide, which of course is a weekly tirzepatide-like half-life. Yeah, absolutely. Got it. Monotherapy, amylin data, we could have that year-end, and then combo, we could have that year-end 2025 or early 2026. Early 2026. Yeah, I mean, again, to your point on mid versus late, I think we'll have it. If we have it the last week of the year, we'll probably release it in January. All right. More data to come towards the end of this year from your oral peptide platform. Can you talk a bit more just about, you know, like why oral peptide? I think you guys have also talked about the bioavailability and scalability of this in comparison to other oral peptides in development. Yeah, I mean, I think the why oral peptide is from our perspective, if you can make them scalable, oral peptides let you do with orals what injectables can do, right? There's no way you can ever get there with a small molecule, right? Of course, the small molecules are scalable, and to date, peptides have not been scalable as orals. This is, I mean, it's fundamentally just an API problem. The bioavailability actually has a fundamental issue, isn't actually that big a deal. Low bioavailability drugs are fine if you can make enough API. If you need 50 mg or 100 mg a day of API, and this is the semaglutide problem, it's just not a scalable construct. Our challenge to ourselves has been, we kind of, it's easy to see the target profile. You're getting the peptide in. It's going to do what the peptide does, right? With MET-097i, we kind of already know what that looks like, you know. You know, how low can we get the dose? How do we dial that in? Maybe Brian, you can speak to what makes our doses lower and what makes it scalable. Yeah. I think the absolute key to our platform is just the potency of the peptides. Right? If you just sort of think about it from an injectable standpoint, what one would need with tirzepatide or Viking, given it's the same amino acid sequence as tirzepatide, is to get to a 15%+ weight loss, you need about 10 mg. For semaglutide, it's probably 2.4 mg injectable, or maybe a little above that. For us, it's about 1 mg. Right out of the gate, if you took those three, Viking tirzepatide, you took sema, and you take us, if you actually had everything be equal, you need 1/10 the dose of MET-097i versus Viking. Crudely, if you just sort of look at their data and say 100 mg, which is clearly not a day, it's clearly not scalable. If you wanted that level of efficacy, you're just starting at 10 mg with MET-097i. There's another feature that's really, really important. Potency is the key. You have to start there. A lot of these peptides, sema, tirzepatide, therefore Viking, that were developed, they were developed first to be injectables, which means they never looked at intestinal stability. Lo and behold, they're not stable in the intestine. We eat protein, we digest it up. That's what we do. We chew up peptides very efficiently. Our peptides are made to be stable in the small intestine. What that means is when you deliver a sema or a Viking, you have to deliver it to the stomach because if it goes to the small intestine, it gets chewed up. We don't absorb things well in the stomach. If you take anything with food and water, your stomach dumps acid in it, dilutes it out. That's why it's a food and water effect. Our peptides are stable to the small intestine. We can use very conventional formulations, simple enteric coatings, simple excipients that people have used before, and now we can actually get better absorption as well. By having a stable to the small intestine peptide and a highly, highly potent peptide, so we don't have to get as much in, we can now get to these scalable levels. That's really the secret. Without food and water effect. Without food and water effect. That's up to you. You guys have a very differentiated and broad pipeline. If it's possible to say, like looking out one year from now, if you could point to your top one or two highlights from the portfolio that you would like to see achieved. Yeah, I mean, I think we're obsessed with this idea of maintenance because ultimately we think this market becomes all about maintenance. I think we're going to have lots and lots and lots of ways to deliver great well-tolerated weight loss, some from our portfolio, some from others. The question is, how do you maintain that sort of shield? Again, that Naveed Sattar at ADA, I think, nailed this, and we keep using this internally. These mechanisms are a shield against an obesogenic environment. You need your shield up for 10, 20 years, right, to avoid regaining weight. What's the most scalable way to do that? Certainly monthly therapies are a big step forward, and we're excited to be part of that. Prodrugs that can go quarterly. MET-815 is a prodrug of MET-097i. We're looking to get it into the clinic by the end of this year, early next year. We'll be kind of sharing more on kind of when data is coming. It's so long-acting, you have to wait a while from dose to data release. We're incredibly excited to be kind of taking this backbone of an incredibly stable long-acting peptide, using the prodrug to blunt the PK, which is really the issue that kind of limits you in terms of how much drug you can put on board, and then exploring how long of a dose interval you can get to for kind of a maintenance switching strategy. Can you get to quarterly dosing? Of course, we're looking at a similar approach across every hormone target we have in our portfolio: PYY, amylin, glucagon, et cetera. Lots more to come on that. Five years from now at ADA, we think we're going to be looking at flat curves, not convex curves. It's going to be how few injections do I need to maintain that flat curve? Yeah. We want to be ahead of the game and ahead of the field on that. We're excited about what's next there. More to come on that. A lot of exciting updates. Thanks everyone for being here, and we'll stay tuned. Great. Thank you so much. Thank you.