Welcome to day one of Cantor's Global Healthcare Conference. For the next session, we have the pleasure of hosting Structure Therapeutics. Representing Structure, have Ray Stevens, CEO. Ray, pleasure to have you here. Prakhar, thank you for having me. Big year for obesity with a lot of data readouts We'll get into that, but maybe if you have any introductory remarks about the company and the key priorities right now. Yeah. Absolutely, Prakhar. So you know, we're what we're most excited about is and why we built the company, it's really around accessibility. And what we're looking forward to, you know, this year, in particular, this has been a transformative year, I think for patients. They're gonna have finally have options, you know. I think the the GLP one area was really, you know, the peptides really created this market in in many of the opportunities. But I think that it's gonna be oral small molecules are really gonna be what really grows this market as we see it becoming more primary care physician oriented and and orals give that flexibility. Know, that initial we think small oral small molecules will become, you know, the first line, for patients to go in from that primary care physician. Sometimes I think what the investors and analysts focus on the the endocrinologist in that market where this field came from, but it's really the primary care physicians is really the future. For structured therapeutics, you know, the company itself was founded around the around the principle of accessibility. It's what we have over the kitchen sink. We have our lead molecules called aleniglapron. We have two data readouts, later on this year, Access and Access two. Access, goes up to a hundred and twenty milligrams in dose. We think this is comparable to ofligipirone thirty six milligrams. And then we're also, quite excited about our access two study that will also read out at the same time. These are both thirty six week studies. Access two allows us to go up to a hundred and eighty and two hundred and forty milligrams in dose that, you know, gives us the opportunity to see potentially, increases in efficacy now that we have a once every four week titration step that we can use, within this thirty six week time period. So we're very excited about the end of the year data readout. And then the other is our amylin two six seven one. We have the only oral amylin small molecule that we're aware of. That will enter the clinic later on this year. By the end of the year, we see both the leniglipiran, our oral GLP one, selected GLP one small molecule, and our amylin two six seven one small molecule as monotherapies. We can also do them in fixed dose combinations as we can also add in our oral GIP and our oral GCG. So we're the only ones that we know have a full portfolio of all small molecules against all the peptides that are out there. Great. Maybe we can start with the alpha glipron data. We saw the obesity data and then the diabetes data as well, and then now obesity plus diabetes data. So what's your overall take on the data and the implications to oligopril? Yeah. We we have tremendous respect for Eli Lilly and for orfaglipirone. We think orfaglipirone is a good molecule. We look at the totality of the data. The first thing that we looked at with the data being released was safety. So particularly I'm talking about off target safety. Were there any liver tox signals that were observed? And what we've seen now, you know, this is a molecule of oligopril that's been seen in a in a large patient population. They have not seen any safety signals. So that's very, positive. For a small molecule, that's something that one really looks at very, very carefully. So that's one. Second, in the study that we just saw, we've seen ofligipron go from phase one to phase two to phase three as they've gone from weekly titration once every twice a week to once every three week titration steps to now in their phase three, once every four week titration steps, we see this improvement in tolerability. Again, is consistent with what we've seen from the peptides. Would it hold for small molecules? Yes. So we like that they're seeing an improvement in tolerability with the once every four week titration steps. So we think this is this is important. It's what the body needs to adapt and evolve. And then on the efficacy number, you know, we know that there was a market reaction to the obesity data with one expectation and the number coming in lower than that. You know, look, a molecule that can be made for the masses, a molecule that's safe, a molecule that does not require cold storage, and that can truly be manufactured at scale with no dietary restriction in the morning, that is a molecule that is really made for the masses. So we think of olfaglipperon will be a market that will be well received on the market. We're looking forward to seeing that. We also think though that this is very positive for structured therapeutics. We believe that we have the potentially best in class oral GLP-one small molecule for a number of different reasons. You know, based on safety we've always said, off target safety, you know, we're very proud of our our rat Noel. Based on efficacy, going to one hundred eighty and two forty, we know the dose proportionality that we have more room for efficacy improvement. Our manufacturing, we know that we have, you know, we believe to have one of the best manufacturing approaches to manufacturing our molecule, no chiral centers with chiral separation. And then lastly, why we're also excited about oleniglipperon, our molecule is combination. So we know that we can combine a linaglipperon with a with an amylin, oral amylin, with a oral gift, with an oral GCG, or other medicines like a PCSK nine or an SGLT two. So we like our position. We think that orfaglipperon data was good for the field, it's good for patients, and it's good for structured therapeutics. Okay. And maybe for the upcoming AXIS and AXIS two trials, a broader question because clinical trial execution seems to be now very important in obesity trials. We're seeing some high discrimination rates on the placebo arm as well across some of the recent trials. So what steps are you taking to mitigate that? Yeah. So I think this is something that that is here. The field is evolving. You know, we we know that it's in the news all the time. GLP ones can cause nausea. We see them on the commercials on TV and all the time. It's in the news. And so, you know, we think that nausea is a very subjective, sort of metric. The metrics that we should really be looking at are more along the lines of vomiting. That is a very objective metric to sort of look at. Discontinuations due to AEs, that is very objective. So Prakhar, to your question of what can we do to help sort of mitigate this, we have seen higher discontinuation rates in in some of the placebo groups as an example. One of the things that we just announced a couple of weeks ago, we announced three new studies that we're doing based on confidence in eleniglipperon. One of the things that we added in was an open label extension to our access study. The primary reason why we added that in was listening to the physicians and listening to the sites saying, look, plus people, individuals that are on placebo, they know that within the four to first four to eight weeks. And they're in this trial because they wanna lose weight. That's what they, you know, they sort of look at. And so we made the decision to add an open label extension so that individuals, they get the good health care during the trial, but then they have the ability, the option to go into the open label extension. So whether you're on placebo group or if you're in the lower dose groups, you can then, participate in the open label extension to experience the drug. So that's that's one example of what we're doing, and we're constantly trying to think creatively how can we continue to evolve our clinical trial operations to to run these trials as as well as possible. And you announced several updates during the last earnings. Open label extension was one part, but there were other trials that were announced as well. So maybe just walk us through the rationale and what really drove that decision? Yeah. So there were there were five total sort of updates. So I just mentioned the open label extension on access. We also did an extension on access too. We also announced three new studies. The first study is what we call switch. This is really it's also should be considered a maintenance type of study. Individuals that are on that are stably on a selective GLP one, can they seamlessly go over to an oral? We know the discontinuation rate on the injectables is quite high, fifty percent after a year. And and we know that, you know, weight management is a chronic disease. And so by being able to switch over from an injectable to an oral is important. What we don't know is do can they just seamlessly go from one dose at at an injectable over to a high dose or a moderate dose of an oral? Or do we have to retitrate? And so we want to ask that question. So that's the two different cohorts is really to try to answer the question, can it be seamless or do we have to retitrate? The second study that we announced is a body composition, looking at, fat versus muscle. And in this study, you know, we're looking at that question. And then the third study is individuals that have type two diabetes and obesity, both. We know that's a significant population. All of these studies are really being done, to really make sure that we have the best phase three design and being informative to that, and also so we have the broadest label possible. So for example, we do not want individuals that are living with type two diabetes to be restricted. So if we have overweight and type two diabetes, we can get the broadest label possible. Got it. And a lot of these studies are in preparation for phase three as well, so what's really driving that confidence? Is it off of Gripen data or alonigripen data as well? Yeah, Picard, it's really both. It's, you know, we're seeing, you know, what's transpired since the beginning of 2025. In January, the FDA came out with clear guidelines, the first update since 02/2007, for chronic weight management, including no longer requiring cardiovascular outcome studies, but also clearly defining exactly what is needed for chronic weight management. The FDA sees this as a pandemic. They use the word maintenance six times to talk about how people are not continuing on these medicines. And so, you know, it started the year with the FDA, you know, update. We we also have an IDMC like all trials do, and we're continuing to sort of look at, you know, we're not seeing any safety signals, so we're quite pleased with that. We just updated our corporate deck this morning as preparation for this fireside chat. And in there, we have included, you know, our IDMC has approved our Sentinel to go up to one eighty and two forty. So we're now clear to go on those studies, so we're very pleased about that. We've also saw in April, you know, Eli Lilly released the top line data for their type two diabetes and and the very positive data there. And so there's been this growing body of evidence, both external as you said, and internal that says oral small molecules are coming. Ofagliflozin will be on the market next year. So all of this is being done to increase confidence and for us to position ourselves as competitively as possible in the phase three trial. And you'll have the access and the access to trial readouts by year end. So maybe just walk us through what are you hoping to see on efficacy and safety in those trials? Yeah. The the question that all investors wanna know, what's your bogey? And so, you know, what we're what we're guiding everybody to is we think the right comparison is thirty six milligrams at thirty six weeks. So this is our study is a thirty six week study, access and access to readout at the end of the year. Now it gets a little bit sort of complex. Cross trial comparisons are always complex as as is often said. In this particular case, the complexity is in orfaglipirin's phase two study, they did titration steps of once every two weeks to once every three weeks. So a faster titration. What that also meant is they got to their maintenance dose much faster. So therefore, they're gonna see more efficacy by getting there faster, but they may pay the price on tolerability. So, you know, that's the sort of, you know, why it's not quite the fair comparison. As we look at their phase three data, they're going once every four weeks in titration step, which is we're doing once every four weeks in titration step. So we think that's the right comparison. It takes longer to get there. So I think from a, you know, we get to the same stage at thirty six weeks in terms of how long we're on maintenance, so that's the right comparison there. You know, what we're really guiding people to is they should look at both of those numbers. It's not I don't think it's right to necessarily pick one or the other. So in the orfaglipperon phase two data, you know, the at thirty six milligrams, it was eleven point two percent. We don't know what the number's gonna be in the phase three. What people are gonna do, September 17 at ESAD in Vienna, we will see the data itself, and people are gonna draw a line at thirty six weeks, and they're gonna, you know, bring it down, and that's gonna be the other number that's gonna give us a range of numbers. In terms of tolerability, we're not gonna get the same breakdown in phase three, and so we're gonna have to rely on the phase two data for tolerability numbers. Right. Yes. I mean, I think, obviously, Street is getting past focusing too much on the weight loss numbers, specific numbers around weight loss. But as you mentioned, tolerability is going to be important. So vomiting, diarrhea, discrimination, are those some of the obviously, these numbers will be important. So why is phase two the right comparison and not phase three? Because we're not going to have the phase three data. We're not going to get a breakdown at thirty six weeks. I I don't think Eli Lilly's gonna do us a favor and and give us those numbers at thirty six weeks. We're gonna what we we only have we can only look at what we have, so we're gonna they gave us seventy two week data. It's not the right comparison. So I agree with you, Pikkar. It's not perfect. It's the best that we can do. We will look at the the Manhattan plot of tolerability, but even that's not perfect because it doesn't break it out into overall numbers. We can only see which one of the plots we we like those plots cause it shows you when you start on drug, you have tolerability challenges the first few weeks, and then it comes down. And what you wanna see with your drug is over time, the tolerability comes down and flattens out, and that's that's what we saw so far at least in the data that we've seen to date with the type two diabetes data. Okay. I did want to talk about the how you perceive the market opportunity for urals. There's obviously two camps out there whether urals expand the market or whether they are more focused they get positioned as a maintenance therapy or maybe switch patients over from an injectable therapy. What's your view on the biggest segment for the market? Yeah, so what we're hearing a lot as we do our market research and continuing to talk to, you know, the key opinion leaders and and the physicians as well is the really good news, patients are finally gonna have options. Right now, they don't have options. And we know the discontent you know, the number of people stop doing the injectables is significant. More than fifty percent stop taking the injectables after a year. So good news, their patients are gonna have options. Now, we see the real driver. We think that analysts such as yourself and investors traditionally have looked at the endocrinologist, the specialist, because that's where this field came from. We see the real market opportunity is primary care physicians. It's going to your general, you know, your GM and and asking your GP and ask them to go on this drug or the nurse prospect practitioner, or physician assistant. And so, you know, we think that's really what's gonna grow this. So as I said, peptides started this market. Small molecules are gonna expand this market, oral small molecules. So, you know, we think that 70% of the market is gonna be from primary care physicians going forward. And and they many of them prefer oral small molecules because it's what they're used to. It also you know, the number one question we ask a lot of physicians, we always think about what's the design of the next generation molecule? What do you want? We ask every physician this question, and they give us the same answer every single time. We want flexibility. I do not want calls in the middle of the night saying, got nausea or I'm vomiting. What do I do? They want flexibility. And and with oral small molecules, you know, that gives them that flexibility of what happens in the real world? Cut the pill in half. Skip a dose. You know? In clinical trials, we don't encourage that. You know, we these are carefully sort of regulated and carefully monitored, but in real life, that's what happens. And so we hear over and over again from primary care physicians, they want flexibility, and oral small molecules give them that flexibility. And as you think about the competitive landscape for oral GLP-one, especially for orfoglipron derivatives like aliniglippron, like, what what do you see and how do you stay differentiated given there's always so much news coming out of markets like China? Yeah. Absolutely. So our our our research is in Shanghai, so we're very familiar with what's going on in the landscape in in China, so we continually sort of monitor that. For structured therapeutics, we have the second most advanced oral GLP one small molecule, alenaglipperone. So that that's an important position and the learning that comes from that. We also are taking a very multigenerational approach, so we're constantly making next generation molecules. We didn't stop after just one. We're very inspired by the statin field where mevacor and zocor are one and two. It was Lipitor number six ten years later. So we constantly work on multigenerational approach. And then we also have the ability with our amylin, oral amylin in a multigenerational approach there, We can talk more about amylin. We also have our GIP and our GLP. So it's really the whole portfolio. We have this strong portfolio. It's not just one single molecule. So having second most advanced, the combinability, the multi generational approach positions us. We we really like our position, you know, quite a bit. At the end of the year, we'll have the data readout, so we'll learn more there. But competition is constantly happening. This is an important space. There's a lot of opportunity. And so, you know, I I like the the Andrew Grove's book, Only the Paranoid Survive. That's on my bookshelf. That's a really important philosophy to have. Great. And several companies including Lilly, I believe are working on different formulations as well. So maybe if you can speak to the work that you are doing, to further optimize the formulation for oligopril? Yeah. So we we started working on formulations ten years ago. We knew we've always viewed this as you need to have the best molecule, you but also have to have the best formulation and the best titration. We that's kinda how we viewed the landscape, very, very early on. So we we continue to invest in extended release technology, gastric retention technology, a lot of different approaches. The you know, one of the things that we've been surprised at but quite pleased, over a year ago we announced our capsular tablet conversion. And people asked us, why are you doing that so early? Isn't this sort of earlier than usual to switch from capsules to tablets? And what we said was, you know, it's really about scalability and reproducibility. I'm really proud of the team, of the job that they did on the tablet. Our tablet continues to be king of the mountain, you know. We're really pleased with how it's performing. It's our best formulation still to date, but we will continue, doing research into formulation. You know, we're not expanding into other targets and doing all these things. We're really focused on these four receptors in the combination, in the formulation to make it's part of our life cycle management process. And you've talked about combinability a few times. Like what what is so special about alenagliptor that makes it more combinable than let's say arfagropropone? Yeah. So one of the things so as we designed the molecule, had four principles in in mind. First, we had to design something that was that had good efficacy. So that was, you know, obviously, the molecule has to work. Second, it has to be safe. So again, we really like our safety profile. I'm talking about off target safety profile, immediately. The manufacturing, talked about that a little bit. The combinability, as we manufacture this, there are certain properties of the molecule, of the molecule itself, of how we how we formulate it, how we can mix it with other molecules, DDI type of effects that we also sort of think about. So we try to consider all those factors as we want to as we designed oliglipperon. And then now that we're developing, our amylin small molecule, we're thinking about the same exact thing, combinability. DDIs, the chemical properties, will it you know, can we truly sort of mix these things together in the formulation that we have? Do we have to use, you know, some sort of you know, we think about the pill and pill burden a lot. Again, this is something that impacts the patient. We always have the patient in mind with everything that we do. And so, you know, what's the size of the pill? Is it layered technology encapsulation? So we we consider all those factors in combinability. So it goes into the but it starts with the molecular properties of the chemical itself. That's a good segue to the oral amylin ACG ACCG two thousand six hundred seventy one. So maybe just give an overview of how does it compare relative to the injectable amylin analogs that are out there? So 2,671 is a molecule, so I'm really proud of the team. This was not an easy, an easy scientific achievement. The the complexity of amylin is that you really have two receptors, calcitonin and amylin, and and often we'll call them DACRAs, dual amylin calcitonin receptor agonist. So what we used as our benchmark for our first molecule was cagrelinotide from Novo Nordisk. We think that, you know, that has been the gold standard to date. We like cagrelinotide's properties. We think by itself it showed really good tolerability even in the phase three data that we just saw. So we use that as our benchmark. Our first generation is a DACRA. We also follow very carefully petrolinotide from Zealand. We think that's a good a good molecule. Say hi to Adam Adam for me tomorrow. And so that that became our first generation. There's there's a big question in the field, which is better, a DACRA or a sera? So we've been very clear to tell everybody, don't be surprised that we have multiple DACRAs or seras. Being first oral, we want to have multiple scaffolds, you never quite know what's gonna happen. So it increases our probability of success. The argument around the sort of SARA versus the DACRA, the selective amylin receptor agonist is, you know, is there an added improvement of selective weight loss or tolerability? And our short answer to that is we don't know, but we want to study it. And so we know this is approach that Eli Lilly is taking. They're looking at both. We're looking at both as well because we have the ability with oral small molecules. Others are picking one approach or the other. Okay. And you do plan to announce another Amlan candidate. This one, 2671 is a dacraft, so is it fair to say that the next one will be a more selective element? No. We're parallel processing Dacras, so we're looking at multiple chemical scaffolds. So again, with GLP-one, everybody thinks there's two scaffolds. There's actually four scaffolds, and we parallel processed all four of those, and we continue to. With the DACRAs, we're gonna look at multiple scaffolds. So, you know, that you know, don't be surprised if the next gen is a another DACRA. We're looking at it both you think about the g o p one space, danuglipperon versus ofogliparone, the lessons learned, the same thing's likely gonna happen with amylins. So we think it's it's the right thing to increase probability of success by having multiple chemical scaffolds. It also helps with our IP strategy. We've been very aggressive, you know, in terms of our IP filing to make sure we can capture as much intellectual property space as possible. The CERA, we continue working on, so, you know, we're we're running these neck and neck. Okay. And so how will the initial clinical development look like for the oral amylin relative to what you did for eleniglipperone? So we learned a lot of lessons from eleniglipperone. You know, one so right now what we're doing is the GLP tox studies as we prepare for phase one. The first, the SAD, will be very traditional, you know, single ascending dose, and and that's really to give us information about the pKa properties and the dose that we want to go into. The you know, one of the big learnings for us is whether we do a four week study as a MAD or whether we go straight to a twelve week study. You know, we we don't think we learn a lot from a four week study. 50% of the weight loss is from water, and so, you know but the reason we do the four week study is because we have one month of tox data, and and that's why people will do a one you know, a four week study and then a twelve week study. What we're thinking about doing is we're thinking about going straight to the twelve week study, because speed speed is of the essence. We not only wanna get our amylin small molecule through phase one because it also impacts we wanna start doing fixed dose combinations, and so we can't do that until we finish the the phase one. And that we think the phase three data, sorry, the the twelve week data will be much more informative, to really tell us how how our two six seven one molecule is working. So that's one of the learnings that we've taken from the GLP one field that we're applying to the, I'd say, the amylin field. And so where where do you see the opportunity for oral amylin? Is a monotherapy or combination? I I see it as both. I think the oral amylins, again, if the hypothesis holds up about better tolerability and selective weight loss, that's that's important. I mean, what what is the what does the market really want? Most 70%, based on our market analysis, 70% of the market out there wants 10% weight loss, and they want no tolerability issues, or they want minimal tolerability issues. That's what we hear from, you know, from the physicians and the patients as well. And so, you know, we see an opportunity for monotherapy. But if we want more weight loss and one of the things I love about small molecules, we can really play with the with the ratio. Is this a one to 10 GLP one to amylin, or or one to two, or a five to one? We can really play with that ratio to get the right efficacy while also maintaining the right tolerability profile. And so that's one of things that we're really excited about is, again, part of our life cycle management approach is fixed dose combinations in different ratio to find that right sweet spot for maximum efficacy in the best tolerability profile. Okay. And maybe one question two questions longer term. First one, you highlighted this as well. You've done a lot of work on IP and building a whole portfolio on the IP front for GLP one and Amlin. Why why do you feel like this is becoming more important in obesity space? So what what we're seeing, you know, when the you know, when when a patent gets published, there'll often be many different groups that will jump on that patent, and we and we call it patent busting, and it it's very common sort of practice, to look for a better molecule. And and in order to get a patent, it has to show advantageous properties. So, you know, as we think about the GLP one space, we saw a number of different groups all around the world jump into that particular scaffold, including ourselves. You know, we did that as well. And that's why we we have more IP around oral small molecule for GLP one than anybody else out there, overwhelmingly more. And we'll take the same approach with with Amylin. So, you know, one, it's a competitive space. It's a very competitive space, so IP is important. So I think that's that's sort of part of it, and and we continue, you know, with that sort of strategy. And last question, longer term, what are the latest thoughts on bringing on a partner? So we've said from the very beginning in terms of partnership, you know, what we have over the kitchen sink, making medicines accessible to all. That's what drives us. We want to be measured by the number of patients that these medicines help. And this is the overall g o p one field in general. They really are remarkable drugs, and obesity is a pandemic, so it's really important. So based on that accessibility, we we've always said we would like to have a strategic partner for commercialization. What we've also consistently said is that, you know, phase three, we cannot do 10 phase three studies. It's not, you know, as a small biotech company. With the new FDA guidelines that just came out in January, you know, chronic weight management is a is a manageable phase three study. But we can't do the other nine. We wanna do sleep apnea. We wanna do mash. We wanna do CKD, type two diabetes. It goes on and on. We can't do all those studies to really realize the full potential of eleniglipperon. So, you know, we continue having dialogues, you know, with with strategics. We will continue having those conversations. Okay. That's all the time we have today. Thank you, Ray, for joining us, and thank you to the audience for listening in.