All right. Welcome, everyone, to Jefferies 2026 Global Healthcare Conference. My name is Roger Song, Senior Analyst, I cover SMID Biotech. It is my great pleasure to have the fireside chat with our next company, Structure Therapeutics. We have our CEO, Stevens. Welcome. Thank you, Roger. Good to be here. I think we've been at Jefferies every year for the past couple of years. Yeah. Good. Yeah. Great. Before we dive in, a lot of the good discussion today and then heading to the ADA, but give us some state of our- where Structure Therapeutics right now, and then what people should pay attention for the coming months, year. Yeah. One of the things I think that we're most excited about is, let's go back even just six months. There was this whole debate: Is there room for orals in the GLP-1 space? Injectables are just fine. Is there really a need? Is there really a market for oral pills? Now fast-forward, we had in January at JP Morgan, we had sort of the release of Oral Wegovy. In April, we then had the release of Mounjaro, and they're not even advertising yet. They've already captured 14% of the market, and actually, it's all growth. 80% is growth of the market. I'm smiling up here because clearly there's a market for oral pills in GLP-1. In fact, we think it's the preferred route that people want. I think the market is going to segment into those that want an oral pill and once-a-month injectables. I think we're going to start to see this sort of divide. What happens to the weekly injectables, we'll see what happens over time. It's still the early innings in this space. From a Structure Therapeutics perspective, we're really excited because we're perfectly positioned. The data that we released back in March. Showed best-in-class efficacy, 16%, and still no plateauing. We think that, and we combine that with our portfolio, the Amylin, our aleniglipron, our glucagon. We're feeling really good about the oral market for GLP-1s, and in particular, long-term maintenance, which we know is a real need in this space. Yeah. Awesome. Yes. I think that hits very well. By the way, you've been saying 2026 is the year of the small molecule, or oral in general, right? I think it's happening right now, so everyone's so excited about the oral launch for obesity. Maybe take a step back, a big picture. Now we have two oral drugs on the market, I think you hit the highlights about how we think about this dynamic going to look like, in the near term a bit longer term. You mentioned this is 80% of the script coming from new patients, I think, is that surprising to you, or you think this can actually continue the trend? Yeah, like I said at the very beginning, Roger, one, we've been hearing for years, injectables have the space covered. Is there a need for oral pills? Again, I'm smiling up here because oral pills, there's all this pent-up demand. Why is the sales of oral Wegovy been so strong? It's clearly pent-up demand. There's a lot of people that want an oral pill versus an injectable. Then you think about this globally. One, it's really reassuring to sort of see our thesis, our hypothesis was there is a market for oral pills. Right now, it's already captured in five months. 12%-14% of the market. We think that's going to go somewhere between 30%-50% of the market will be oral pills. With that, with our aleniglipron, we think we're in a really good position with a best-in-class profile to be in a really good position, both for our monotherapy, aleniglipron, that's about to start phase III, but also our amylin ACCG-2671, that's just finishing phase I, and w e're about to get into a phase II-A study. Yeah. Great. The good thing is, injectable, they are efficacious and a lot of people are on drug, they'd probably be happy. The good thing is for oral, you are expanding the market and then benefit more patients on one hand, and then on the other hand, you're not really competing against some of the incumbent, and rather you are creating a new market for the oral ones. I think right now what we've seen in the first five months is, it is pent-up demand. It's broadening the market. That's clearly, I think, the dynamics, and it's still way too early to tell. Again, Mounjaro hasn't even started advertising yet. I think we're going to see the market continue to expand. I do think that the orals are eventually going to start to eat into the injectable market. We're doing a study right now that we call our switch study- Yep. -where individuals that are on an injectable, we know 85% of people on once-a-week injectables. 85% discontinue after two years. Yes. Different reasons for it, whether it's coverage, whether it's the needle itself. There's a really big demand. I think that the orals will also start to eat into that injectable market as well. Roger, the FDA came out with new guidelines back in January 2025, just last year. One of the terms that they highlighted was maintenance, six times. Why is the FDA so focused on long-term maintenance? The answer is they're really worried about people going on this class of medicines, losing weight, then going off the medicine, the yo-yo effect. Losing weight, gaining weight, back and forth, creating a new health crisis. There is a really big unmet need for long-term chronic care. in this class of medicines. Yeah. Got it. All right. Maybe we talk about the aleniglipron for a moment, and then I definitely want to talk about the Amylin, because that's a lot of patient pay attention, and then also that's a very first-in-class type of drug. For aleniglipron, we're heading to ADA. We're all- Yeah -going be there. A lot of investors will be there as well. I know you, at this moment, you are embargo for whatever you would present there. What is the high-level expectation investors should have, and what you think is very meaningful you want to share with people? Not necessarily you tell us anything you want to share. One thing for everybody, ADA does start on Friday. We are under embargo until Friday. We have a presentation, Dr. Julio Rosenstock, who is one of the premier KOLs. Love it. Yeah. Yeah. We're really excited. Dr. Rosenstock is going to present our ACCESS study at 12:45 P.M. Central Time on Friday afternoon. Excited about that. The rest of the presentations for ADA, the embargo gets lifted at 7:30 P.M. Eastern Time. Mixing up my time zones. The rest of the presentations will be released end of Friday. Excited, and that includes our Amylin data. On the ACCESS data, we released the initial data back in December, and then we had an update with our open label extension. That's a study that's going out to 72 weeks. Dr. Rosenstock will present that. We'll also include some additional data, as well as how we look at what we call the patient journey. We have these cumulative tables of AEs that really tells the sort of story, a collection, the accumulation. Roger, have you been nauseous in the past nine months? Probably once. That shows up as one of those sort of time points in these studies. We're going to focus on the patient journey, what exactly do they go through? For example, there's been this hypothesis, if you're on an oral and you skip a dose, what happens? Do you have to sort of re-titrate? We're trying to answer those type of questions that we think are important. That's going to be the Friday presentation. One of the other presentations that I want to sort of highlight is we're going to be sharing non-human primate data, still pre-clinical, on our Amylin -2671. That's going to be both monotherapy as well as combination, and non-human primate really is probably the best model before we get to human trials. I'm so excited about that data as well, both monotherapy and combination. While I'm talking about Amylin, we will release our phase I SAD study for our oral Amylin small molecule. The only small molecule we know for Amylin out there right now that's in clinical trials. We'll be releasing that data in Q3. We will immediately start the phase IIa study. That'll be a 12-week study right on those heels. Awesome. All right. Amylin, we'll definitely talk about that. In terms of ADA, it's great you have the biggest KOL to present the ACCESS data, and we're definitely going to learn a lot of detail in the subgroup and then some analysis. That's great. The other thing is, feel free to comment to the degree you feel comfortable, because we have another small molecule will give us longer term phase IIb data, 26, 36 week. A lot of people are looking for that to compare, contrast with Structure. I'm talking about AstraZeneca, the drug. How you think about that, right? It is a more validation to your point, or it's create more competition, and what will be a scenario you think, a base case to you for that program? Yeah. I think first of all, I think it's really important for the field that there be multiple molecules. It's a competitive space. There should be competition. There's no question about it. I think that the data that we released back in March, 16.3% weight loss with no signs of plateauing. That's a high bar to meet. Beautiful. We are now reaching injectable levels of efficacy. I remember I was just talking to one investor this morning. We've been talking since ADA, that was in San Diego four years ago. Yeah. There was this hypothesis, orals could never reach the same efficacy as injectables. It's just different route of administration, everything. We're now achieving that, and we're really proud of that 16%. That's significant. We're looking forward to the data. The data that you're referring to is going to be on Monday. Yep. We're looking forward to seeing that. We think the bar is pretty high. There's also going to be room for multiple products. At the end of the day, it's all about giving patients as many options as possible. That's the way we sort of look at it. Yeah. By the way, we want to note here is they did leapfrog or skip some of the earlier phase IIa without doing the 12 weeks, right into the 26, 36 week, rather than you structure and then you did a full-blown phase IIa and then the phase IIb. I think it's more de-risk and in terms of those finding. Also you are full speed ahead into the phase III, and then we'll see what's the decision there. At this moment, I always say you are second to the market in terms of the small molecule. Roger, you're bringing up a really good point. I think that we have done more phase II studies than anybody on an oral GLP-1. What I mean by this is we have our ACCESS, we have our ACCESS II, we have our body composition study, we have our type II diabetes with obesity, we have our SWITCH study. I'm probably missing another one. We have a number of different phase II studies, and our mentality, the mantra in the field is never do something in phase III that you don't already know the answer to. We know the answer to pretty much everything. We know how to do the DEXA scan in terms of body composition that's now required by the FDA. We know what the starting dose is, where we see really good tolerability. 2.5mg, we've communicated, is the sort of starting dose. We know our dose. We're not going to a dose that we don't have significant data in already. We're feeling really, really well prepared. We had a very straightforward meeting and a phase II meeting with the FDA. I know the FDA is going through a lot of turmoil these days, one place where they've been, at least our experience, very productive conversations. Because we had such a wealth of data, and everything, it was very straightforward. We're all prepared to initiate phase III in Q3. Yeah, that's right. You did mention you have quite a few phase II or phase II-like kind of study, and then you will have some data Q3 and the Q4, and then you just mentioned phase III star will be Q3. How much data you need before your star, and then how much data later on can be incorporated into the pivotal program? Yeah. First, we don't need any additional data to start phase III. We have everything that we need, we have the full green light for that. The additional studies are really about sort of additional learnings. For example, the open label extension, and this is where I really want to give tremendous credit to our clinical team. I think Dr. Blai Coll, our CMO, he's considered to be one of the top CMOs in this obesity space, at least that we hear from a lot of the KOLs. They really enjoy working with Dr. Coll. Blai was the first to propose doing an open label extension. We did this on top of our ACCESS study. Yeah. That was a 36-week study. To me, what was so important about that was doing another 36 weeks on top of that open label extension. Why is that important? Placebo rates. We know that there's a placebo issue where people, you know within 6-8 weeks if you are on drug or not. Do you really want to continue a study, if you're in the sort of placebo range? What we saw was almost 90% of people that were allowed to sign up for the open label extension, an additional 36 weeks- almost 90% signed up for it. That tells you two things. One, that mechanism, and we had a low discontinuation rate in the placebo range. One, it really helps maintaining those discontinuation numbers. Second, having almost 90% of people continue on in a study and want to sign up for another 36 weeks, they must have really liked the drug. The drug really worked really, really well. That was another thing that was really reassuring to us. is that they wanted to continue. In fact, one particular participant was like, "How can I sign up for sort of the next study? Yeah. Absolutely. Aleniglipron full speed ahead into phase III. We're going to see some meaningful data at the ADA, later on for the additional phase II data to support all everything we try to do here. Circle back on the Amylin part. Start with the high level, you have the small molecule, GLP-1, which we know it's going to be very important for the future obesity space. The Amylin is a target, probably it's just next to the incretin overall. Why you think a small molecule Amylin is so important? One is how important that to the field, to the obesity space, and then how important that to Structure? Yeah. Let me frame this in the perspective of GLP-1s. Again, this conversation that we started, Roger. Is there a need for an oral GLP-1 pill? Clearly the answer is yes. The market opened up 80% of new participants. It's really growing the field, so that's really important. Let's frame it from that perspective. By the way, one of the studies that I wanted to answer in the previous question, Roger, that's related to this is we're also excited about the switch study. Yep. This is individuals who are on an injectable. Can they move over for long-term maintenance? Again, we have this 85% number of people that discontinue after two years, that are on injectables. We ask the question in that SWITCH study, do they have to re-titrate? Do they basically have to stop, re-titrate on an oral pill, in order to get back to that sort of efficacy? The scientific question is, can they go seamlessly from a whatever dose at an injectable straight over into an oral? That's the scientific question that we're asking. We think that's an important scientific question. Our hypothesis is you do not have to re-titrate. Once you've already gotten used to this class of medicines- once your body has already adapted, then you should be able to seamlessly go straight over to a high dose. We're asking that question, and that's again, really about long-term maintenance. Now to your question about Amylins. It's the same thing. It's about giving patients options. First, we think that there is a market for an oral Amylin small molecule pill, just like there is for Amylins that are out there. There's a number of companies, really good companies, that are trailblazing the area on the injectable Amylins. We think that there are those that would prefer an oral Amylin pill. First, we fit that need. Second, the hypothesis is still valid. Amylin is a very validated target. The cagrilintide data that we've seen to date, which is the best characterized out of all the Amylins, it works. It shows good tolerability, and it shows reasonable efficacy. We think that that's also important. We think that sort of developing the amylin, and then the combination, and then again, this is one of the things I'm really excited about this year for 2026 for Structure Therapeutics is we go from being a one product company, our aleniglipron going into phase III, to our Amylin ACCG-2671 going into that phase IIa study. to the combination. We think the combinations, just as we've seen with the combination of, let's say, tirzepatide, GLP-GIP v ersus monotherapy GLP-1, semaglutide, versus now we're seeing triple G's. Combinations are really important. What I love about small molecules is we can really play around with, for example, the ratio. In our combinations, do we want to have mostly Amylin with a little bit of GLP-1, or do we want to have mostly GLP-1 with a little bit of the Amylin? That's something that we can test in a fixed-dose combination. With small molecules, we can really play with that. That's one of the things that we'll explore. in our phase II-A study. Yeah. That's another reason you have a multiple DCE, and then even from the backbone Amylin, you're still testing different ways because the field still not settle what's a calcitonin versus Amylin, then what's a ratio, and then that's it. Yeah, absolutely. Again, I always use the sort of expression, it's still the early innings in this space, as crazy as that sounds. It was only three years ago that Mounjaro came out. I think it was about three years ago. That is fascinating how fast this field is moving. It's still the early innings. There's still so much we don't know, including the Amylins and DACRAs or SARAs. We work on both. There's new data. It was only last year, ADA in Chicago, where we saw the eloralintide data, which was quite intriguing data from that. Really strong efficacy in the tolerability profile. We need to see more data on that, but t his is a field that continues to evolve every week. Yeah. If not every day. Okay. Then in terms of the data we're going to see, I know that's in a human primate, and then at ADA, will we be able to compare or contrast with the other Amylin in terms of the non-human or maybe even the incretin or GLP-1? Yeah. First of all, the data that we're going to be sharing is non-human primate. That gives us a really good handle on efficacy. Again, a really good sort of model for the human data. It gives us a really good sense of the PK as well. We'll get a good sense there. The SAD study that we're running right now, keep in mind, single ascending dose. We give a single pill. We announced back in January our dosing scheme, one, two, five, 10, 20mg. Low dose. It's really to look at two primary things. First, safety. That's really important. Second, we want to look at PK.n Does the PK hold up from the non-human primate? To date, it has. There's no reason to think that it won't, but we want to sort of check that. The third is, do we get some hints of target engagement? We really don't get that from the preclinical models. Particularly what I'm talking about is the AEs, nausea, vomiting. We'll get some degree of target engagement from a single dose, at least based on our experience with GLP-1s. We saw a very low dose, absolutely nothing. That's where we start titrating. When we go up in higher dose, yeah, you see target engagement. Efficacy, people should not be expecting a whole lot on efficacy by taking a single pill. It's just too early on that. Target engagement, we think, is an important way to sort of look at this. Yeah. You mentioned the next step after the phase I SAD later this year is a phase IIa 12 weeks. What made you make that decision, in terms of usually people do four weeks and then versus 12 weeks? These four-week studies, what we've learned is, at least this is our opinion, they're largely useless. What I mean by that is there's no titration. You're basically just sort of giving drug. 50% of the weight loss is water. How meaningful really is it? In this field, it's about speed. It's more efficient for us to go straight from that SAD study straight into a 12-week study where we can have a little bit of titration to sort of get to the point to best inform us for the longer phase IIb study, where we really get the more meaningful information that really helps us learn how to best do the best possible phase III. Yeah. You do mention the combination with the GLP-1. How soon we'll start to see the combination? Is that in the phase II or phase Ib or phase IIa? Right now our plan is now that we have the two monotherapies. Yeah. Aleniglipron that's going into phase III. Our ACCG-2671 that'll be going into the phase IIa. We have the data that we need to then start the combination studies right away. Okay. Got it. In terms of the, we know Amylin as a monotherapy, some people think you don't need to be as efficacious or in terms of the weight loss compared to incretin. Some people say, "Yes, and we can as an alternate kind of a therapy." On the GI tolerability side can be a little bit better. What is your small molecule Amylin ACCG-2671, the target profile you want to achieve? The target profile, the way that we sort of look at it, I'll go into some of the sort of specifics. From a PK perspective, we really look at Cmax, AUC. That's our efficacy driver. We look at Ctrough, so part of our target product profile is really a once a day drug. We think it's going to be more challenging in this space to have a twice a day drug, so it really needs to be a once a day drug. That's important. We look at Ctrough. How much coverage do we have at 24 hours, so that it is truly a once a day. There was this debate with our aleniglipron, and we showed we dosed once a day for nine months. We got the best efficacy there is. Clearly, we were right in terms of how we're looking at the PK properties. We're using very similar principles with our Amylin. Once a day drug, good solid efficacy. We want to see that right tolerability profile. We explore things in phase I, phase II, so that we have the right profile for phase III, which is the ultimate sort of measure that goes into the label. We're using very similar principles, with a few additional learnings along the way. Got it. Understand Amylin, particularly for small molecule Amylin, is a first in class. How likely, after the phase IIa, you can have a discussion with the FDA or regulator to think about the pivotal program, or you want to do another phase? Yeah, that remains to be determined. We're going to look at the data that we have right now, that we have coming up in Q3. We're going to design that. We'll get the phase IIa underway. That's more to come on that. We'll continue to strategize. How much the dose finding or ranging you will do for the phase IIa? Again, the SAD, the S-A-D study is really about finding where do we not see any sort of AEs, and what's the PK properties, all the different parameters. Where do we start to see some target engagement? We want to learn that. That's going to give us our window. Again, we have quite a bit of experience now with the GLP-1 to help us really do the phase II-A and the dose range finding properly. We'll use all of those learnings to integrate into our modeling. Yeah. Okay, good. Obesity space is competitive, and then there are a lot of the bigger player there. Structure is one of the leading company as a standalone biotech company. How you think about the partnership, and then how much you think the angle from both GLP-1, alenigliporn, and then ACCG-2671, Amylin will play into this future partnership discussion? Yeah. From a Structure perspective, it's really a portfolio. We're not just aleniglipron, although that's where we really get all of our credit to date. All of our value is really just on the GSBR-1290 aleniglipron. We don't get a whole lot of credit for Amylin right now. Yeah. That's now we have human clinical data. We'll be reporting that out in Q3. We think that's going to become an important value driver. Obviously, the sort of proof of concept from the phase IIa will be additional. Yeah. One should really look at Structure, and from those sort of eyes, from a strategic perspective, it's really the portfolio. Yep. It's all of it together. It's not just one piece or another piece. That's how we think Structure should be looked at. It really gets back to sort of the combination. When we built this company, It was around life cycle management. Combos are really important. Yeah. We don't get value for that yet, but i t's coming. Yeah. Okay, good. Then I think one thing also, I think it's a very critical piece of the story, is the IP portfolio. I think investors are underappreciating how much you own the space, and not just Alnylam or GLP-1, Amylin, and maybe some of the others we don't even know. Tell us a little bit more about this. I know it's a little bit secretive- Yeah -how much you can say. No, this is something, again, I don't think we get sort of a lot of credit, but the cartoon that I have in my head is we have our aleniglipron or our Amylin as the sort of castle. Yeah. We've built, and for those of you that don't know, we have our discovery in Shanghai. We've had our discovery in Shanghai since 2016, which is really important. There is incredible chemistry resources in cities like Shanghai, w hich is where we're located. You're right, Roger. We have built what we call our IP moat. We have more intellectual property than all the pharma companies combined in GLP-1 itself. Okay. In Amylin, I consider it to be what I call our GLP-1 IP strategy on steroids. We are filing a lot of IP around this. Okay. Our platform, Structure-Based Drug Discovery, allows us to visualize the binding site. We can see all the different pockets, and then with our tremendous chemistry strength in Shanghai, combining that with the IP strategy. Roche came to us. They approached us. with the danuglipron scaffold. We know that there's other companies out there that are going to have to get a license from us for their GLP-1 programs. With Amylin, it's going to be even more so. Yeah. We're really proud of the IP strategy. We're not in the business of litigation. We're in the business of making the best medicine. Yeah. As a business, we also got to protect ourselves, and that's one of the ways that we're protecting ourselves from this insanely competitive space. Yeah. Awesome. I think we touch a lot, and then maybe just last minute, cash position, and then also anything else we haven't talked, but you want to highlight. Yeah. We're in good shape. We have $1.5 billion on the balance sheet. We are fully set for doing the phase III aleniglipron study in chronic weight management. We feel very comfortable and confident given all the phase II studies that we've done. That also allows us to progress our Amylin program, our combination program, and other combos that we haven't talked about. I'm excited, one, about our position. I'm also really excited. I leave this afternoon for New Orleans, the start of hurricane season. Not that that's what I'm excited about. I'm excited about ADA. Every year, it's been fascinating to see such forward progress in the space. With all the things in the world, this is an area where we're really seeing great medicines get developed that are really impacting people's lives around the world. Excellent. I'm going to see you in New Orleans then. I will see you in New Orleans, Roger. Thank you. Thank you. Thank you, everyone. Thank you. Excellent. Right, we've traveled