Conference Transcript - GPCR 2026-09-16

Terence Flynn, Analyst — Morgan Stanley

So thanks for joining us. I'm Terrence Flynn, Morgan Stanley's U.S. Biopharma Analyst. For important disclosures, please see Morgan Stanley's research disclosure website at www.morganstanley.com backslash research disclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Very pleased to be hosting Structure Therapeutics this afternoon or this morning, I guess. We're still in the morning. We have the company CEO, Ray Stevens. Ray, thanks so much for joining us. Really appreciate the time today. Thank you, Terrence. So, again, I think we'll focus a lot on some of the recent pipeline developments. Obviously, you guys had some data out for both Elenaglipron and your oral amylin. So maybe first, just to start on Eleni, you know, obviously the obesity market is growing rapidly here. We're seeing the first two orals enter the market and seeing market expansion. As you think about the profile of Elenaglipron that you guys have generated so far, What are kind of the key features we should think about on differentiation?

Raymond Stevens, CEO

Yeah, I think one of the big key differentiators is our dynamic range. So we can go from 2.5 milligrams to 180 milligrams. What this really translates into is potentially best-in-class efficacy. So the data that we showed last week was up to 16% weight loss. So we're starting to see a separation of the pack where many of the, you know, competing molecules are in that 11% to 12% range. and we're out at 16%, and that 16% is after only seven to eight weeks median on the top dose. So I'm excited about the phase three when we've been out to 52 weeks. You know, hopefully we'll see even more efficacy. But I think dose range and potentially best-in-class efficacy is really what separates Eleni Gliperon from everybody else right now.

Terence Flynn, Analyst — Morgan Stanley

Great. You know, I kind of alluded to this in my opening remarks, But, you know, as we look at the launches of the existing orals, what have been your kind of impressions of what we've seen so far, just from a high-level takeaway side?

Raymond Stevens, CEO

It was about a year ago I was on stage with you, you know, at this same conference. And a year ago, the conversation was, is there room for oral GLP-1s? People were still debating this a year ago. Fast forward only a few months. It was January, JP Morgan, you know, conference, or Rogovi came out. And then in April, we had Fundeo come out. Now, it's only been seven, eight months of data that we have. The orals have already taken 17% of the market, and it's still ramping up. I think the number is 80% are new entrants into the market. That means that it's all about expansion. So what we're seeing is with the orals coming on, there was a big pent-up demand. We're seeing really good launches. Big question we get with Fundayo, has the launch been slower? My attitude is give it time. I think it's just, you know, let's keep in mind this has only been a few months. So they've been fantastic launches. The estimate is market analysis by 2030, 50% of the market is going to be oral GLP-1s.

Terence Flynn, Analyst — Morgan Stanley

Great. And maybe talk to us about scalability. I know that's something else that you guys have highlighted. So as we think about not just the U.S. opportunity, but also the global opportunity and why scalability is so important.

Raymond Stevens, CEO

Yeah, and this is somewhat of a sort of reminder to the previous question. In this space, in GLP-1's class of medicines, one of the other things that's really starting to be appreciated is the ex-U.S. market is just as big as the U.S. market. We're really seeing that this is unique from, I think, a lot of other medicines. Now, to Eleni Gliperon, we designed this molecule at the very beginning. You know, we thought about, you know, manufacturing, cost of goods. We thought very carefully about that. Our tagline for the company is making medicines, you know, accessible to all. So when we designed the molecule, obviously efficacy, safety, tolerability was top of mind. But what was also on our mind was manufacturing. You know, could we make the manufacturing as streamlined and as simple as possible so we could truly get the cost of goods down as low as possible so we could address a very large global unmet need. And I'm really proud of our CMC team. They've done a phenomenal job at really making these medicines at the right point.

Terence Flynn, Analyst — Morgan Stanley

Maybe we'll pivot to some of the recent data that came out. So you had the 72-week access open label extension data. Maybe just give us kind of the highlights from both an efficacy perspective, durability, but also safety tolerability, again, particularly at the 2.5 MIG data.

Raymond Stevens, CEO

So I'll start with the purpose. We've done more Phase II studies than I think anybody else has done in characterizing, particularly for an oral GLP-1. Dr. Bly Cole, our chief medical officer, again, has just done a phenomenal job there. We're really, really happy with the 2.5 milligram dose. Starting at that dose, we saw a 2.6% discontinuation rate due to AEs. This is the lowest discontinuation rate that we've seen with any of the GLP-1s. So first of all, in terms of that aspect, you know, fantastic job. The 2.5 milligram start, we also wanted to see what the physicians are telling us is that what they want is gradual weight loss. They don't want to see that sort of rapid weight loss. So could we have a sort of linear profile, a linear shape to the weight loss? That's important. And we're able to see that. We see weight loss in the first four to six weeks. That's really important. Otherwise, they think, you know, it's not working. They'll give up. So we think that's an important component. But that linear shape of the line is really important. And then so that's the, you know, the 2.5 milligram start. And the start low, go slow really, really works well. And then the question is in that data, 72 weeks of data, safety. What I'm really pleased with is, you know, if we look at these sort of liver talks, you know, ALT, AST, we do not see any issues at all. So we've been in over 800 participants, 72 weeks. This is a very safe drug. So that's really, really important, the safety profile itself. And then in terms of efficacy, again, after only seven to eight weeks, at the top dose, 180 milligrams, we're seeing 16% weight loss. That's significantly above all the competition out there. And I think it's only going to get better from there. So we're really pleased with the elating glyphoron data that we shared last week. And in talking to the KOLs, what they've highlighted is, again, we're separating from the pack and we're able to maintain that solid weight loss.

Terence Flynn, Analyst — Morgan Stanley

Great. I think there's a couple more readouts coming up here in the fourth quarter. So you have a body composition study. You also have a switch study. And so maybe just remind us kind of what we're hoping to learn from those two studies in the fourth quarter.

Raymond Stevens, CEO

Yeah. So next quarter is actually going to be three studies. The body composition will read out. This is where we're looking at fat versus muscle. This is an important question. This is now required by the FDA in this class of medicines. And part of it is, you know, really making sure that we do these studies optimally. We're also starting at 2.5 milligrams, and we'll go to 180 milligrams in that study as well, 44 weeks. The second study that I'll read out is type 2 diabetes. These are individuals with type 2 diabetes who are overweight. And here in our previous type 2 diabetes, we only went to 90 milligrams. Now we'll be going up to 180 milligrams. So we think that's an important readout also. So that will help us to inform the ACCOMPLISHED II study, Phase III study, that's now underway. And then the third study, the SWITCH study, we know that those on injectable GLP-1s, the discontinuation rate is 85% after two years. Most people stop taking injectable GLP-1s after two years. And so one of the big words in the recent FDA update was maintenance, long-term maintenance for this class. What the FDA wants to avoid is what is often referred to as the yo-yo effect. People lose weight, gain weight, lose weight, gain weight. And so we wanted to ask the question, could you switch from an injectable GLP-1 over to an oral? And if you switch, do you have to re-titrate? Or can you start at dose X on an injectable? And can you seamlessly go straight to a similar dose of an oral? That's the question that we're asking in that switch study. So all three of those we'll read out next quarter.

Terence Flynn, Analyst — Morgan Stanley

Maybe just a couple follow-ups on the switch study. I know Lily had some data for Foundeo from Attain-Maintain. Any key differences in terms of design for your trial versus their trials? Everyone's going to do these cross-trial comparisons, but anything we need to be mindful of there?

Raymond Stevens, CEO

Yeah, and I think Lilly did, you know, for Eli Lilly, I think that was a very well-executed study. But Orpoglipron can achieve 11% to 12% weight loss. They compared it to Trisepatide, a GLIP-GIP, and that's putting the bar pretty high. And so what we're doing is we're looking at, you know, with GLP-1s, we think that, first of all, the Lenny Glipron is showing currently 16% weight loss. So we have potentially best in class in terms of efficacy, GLP-1. Can we maintain that weight loss? Or can we possibly, you know, get, you know, additional weight loss as well if you're on a GLP-1? Or, you know, can you maintain to a GLP-GIP? So I think it's really the biggest difference is we have potentially better in class molecule. Can you maintain that?

Terence Flynn, Analyst — Morgan Stanley

And so just because you aren't doing the terzepatide transition, you're only doing a... GLPB.

Raymond Stevens, CEO

Yeah, we haven't updated. What we've stated is that we're doing GLP injectables. It may be a combination.

Terence Flynn, Analyst — Morgan Stanley

Okay. And what, just remind us the size, like how many people are going to be in this one?

Raymond Stevens, CEO

I don't have the exact number off the top of my head.

Terence Flynn, Analyst — Morgan Stanley

Okay. But it's fairly, it's like a decent size trial. Okay. Okay, great. And then on the type 2 diabetes side, again, you mentioned, you know, you previously went up to 90, now you're going up to 180. I'm assuming you're going to gather not only weight loss data, but hemoglobin A1c data. So maybe just remind us what you guys saw before at the 90-MIG dose.

Raymond Stevens, CEO

Yeah. So at the 90-MIG dose, we saw, I think it was around three and a half percent weight loss. And so for those with individuals living with type 2 diabetes, they typically see less weight loss than those without, that are not living with type 2 diabetes. So it was also at a lower dose. So we want to sort of basically test at a higher dose, can we see further improvements in hemoglobin A1c? And that's really the main driver is hemoglobin A1c, you know, for individuals living with type 2 diabetes. We've recently seen some very encouraging data on Fundeo in type 2 diabetes, and so we think this is an important question to ask.

Terence Flynn, Analyst — Morgan Stanley

Okay. Okay, great. Maybe now you alluded to this, but you guys have already moved into the Phase 3 program, so maybe just high-level level set us kind of the scope of that Phase 3 program that started and then how to think about additional trials and other indications.

Raymond Stevens, CEO

So we have two different studies going on, ACCOMPLISH 1 and ACCOMPLISH 2. This data will read out at the end of 2028. There are individuals that are on maintenance dose for 52 weeks. This is the FDA guidelines. Approximately 5,000 participants total. There will be three different cohorts going up to 45, 90, and 180 milligrams. The starting dose will be 2.5 milligrams. Again, what we've learned from all the studies is individuals are very happy at that 2.5 milligram start and start low and go slow. Titration steps once every four weeks. Again, we know that is the right sort of titration step, both for tolerability, but also that linear weight loss that we're trying to achieve. So those are the rough parameters of the... And then one other thing I'd say is, you know, I think, again, Bly has done a phenomenal job at doing additional studies to help us do the best optimal sort of phase three. So one of the experiments that he did in phase two was what we called an open-label extension. One of the challenges in the field are placebo groups in this space. And so Bly wanted to ask the question, if you do an open-label extension where you can extend for, you know, basically in the phase three for an additional year. Does this help with the clinical trial execution? It certainly helped in the phase two study. We believe it will help us in the phase three study. The use of heat maps, again, Bly has been very creative. He was the first to use an open label extension in obesity, first to use these heat maps where we look at the patient journey, what happens if you skip a dose. That has also really helped us understand how to to do the titrations, how to do the steps, and how to have the best possible patient experience as they go through titration phase all the way through maintenance. So all those things combined give us the confidence that the phase three will be very well executed.

Terence Flynn, Analyst — Morgan Stanley

Great. Anything else on baseline characteristics about this population you're enrolling versus maybe the phase two trial?

Raymond Stevens, CEO

No, it'll be very similar phase two to phase three.

Terence Flynn, Analyst — Morgan Stanley

Okay, great. And then how do you think about, you know, the rate of discontinuations due to AEs that would be competitive? I mean, maybe just frame for us that. And then, again, you mentioned the 2.6%. I think you guys saw in the latest cut of the data. Is that the right, you know, level to think about here from the Phase III program?

Raymond Stevens, CEO

Yeah, that was a smaller study and shorter period of time. So, you know, I have to sort of factor that in. We need to be competitive. You know, at the end of the day, we've got to be competitive in all the different categories in terms of efficacy, tolerability, and we do think discontinuation rate. At the end of the day, what really matters, individuals are taking the medicine and it's working, and that they don't discontinue. So that 2.6% rate I think was, you know, we're really proud, again, I think best in class in the field, but that was a smaller study. I'm not going to give a specific number, but we need to be competitive with everybody else.

Terence Flynn, Analyst — Morgan Stanley

Okay, great. And then the second part of my question was just on the other comorbidities you might consider. You know, we've seen Lilly Novo lean into some of these other indications like sleep apnea, for example. So how are you guys thinking about that next cohort of potential trials?

Raymond Stevens, CEO

For this particular, the way that we analyze the field, the foundation is chronic weight management. This is the biggest market opportunity. It's also the market that's becoming, you know, direct pay in terms of growth. And so we are laser focused on chronic weight management as the primary foundation. We're also doing individuals who are overweight with type 2 diabetes because we think that that's also a really important subset as well. That's where we're focused for the phase 3. That's accomplished 1 is individuals who are overweight. Accomplished 2 is individuals overweight with type 2 diabetes.

Terence Flynn, Analyst — Morgan Stanley

Okay, great. Latest thoughts on potential partnership for Eleni? Like, where are we at? Any timelines?

Raymond Stevens, CEO

We continue having dialogues. You know, we enjoy interacting with everybody in the industry. We're laser-focused on execution, as the strategics still understand this space. This is uncharted territory. It's consumer product together with the pharmaceutical market. It's a field that's growing really, really fast. What we think with our Eleni data being best in class, it's highly differentiated. The dose range, 2.5 to 180, is differentiated, all the different properties. And so, you know, we think that, you know, this is going to be, you know, a really great molecule. We're focused on execution. Strategics will continue having dialogues, but we think it's significantly de-risked with this latest data.

Terence Flynn, Analyst — Morgan Stanley

Okay. Okay, great. Maybe we'll move on to your second program, 2671. This is the oral amylin. And again, an update about a week ago from the SAD portion of the phase one. So maybe just talk to us about the highlights for those that didn't see that data, and then we'll dig into some more.

Raymond Stevens, CEO

Yeah, so this is a molecule, you know, many of my sort of friends at other companies, you know, used to say, Ray, you can never make a small molecule to amylin. It's just too challenging. You know, these are peptide receptors, and this particular amylin is a complicated biological system. So first, I'm really proud of the chemists and the biologists. They did a great job at coming up with this molecule. The highlights from the data release that we had last week, first of all, it is an oral small molecule. Second, it has a half-life. We shared PK data, a half-life of six days. This is right in line with the peptides. This is, you know, again, this is something that we knew it was going to have a long half-life. We shared data at the American Diabetes Association meeting this summer. in New Orleans, 60 hours in human primates. So, you know, we're quite pleased. It was actually even longer than we thought in humans. That six-day half-life gives us the opportunity to do a once-a-day dose daily or once-a-week dose. So that's something that we're going to explore in the MAD portion itself. We also were very pleased with the, we had three different levels of target engagement to show that we really do have a drug that works. The first was if you go to a very high dose, do you feel adverse events? If we didn't see anything, people would have said your drug doesn't work. So we viewed that as, you know, something that was important. So at the one and two milligram dose, no AEs, zero. Five milligram, you start seeing AEs. Ten milligrams, you see AEs. So it was right in line with what was expected. Second, we did see, even though this was not a weight loss study, it's a sink, we give people a single pill, but after 17 or 24 days, we saw weight loss. So that was also another sign of target engagement. And then the third, this was very exploratory. In the amylin space, there's a debate between DACRA's dual amylin and calcitonin receptor agonist and SARA's selective amylin receptor agonist. And we wanted to ask the question, the calcitonin component, is there a possibility that this class of medicines could be important for bone health? This is an important segment of the population. And so we evaluated, we looked at CTX1 as a bone biomarker, and we were very pleased to see that we saw a target engagement with CTX1 as well as with bone ALKFOS. So three levels of target engagement in an SAD study, all the information that we needed to educate us on how to do the MAD portion as well as possible. So we will be starting in the MAD, obviously, at one or two milligrams, no AEs, we will titrate like everybody else does in GLP-1s and in amylens, and excited to see that data in the first half of next year.

Terence Flynn, Analyst — Morgan Stanley

Okay, great. Maybe just remind us, like, what is the, what's the benchmark there from some of the early injectable amylen studies? Like, what should we, when we look at the data, what we should, what should we compare it to, I guess?

Raymond Stevens, CEO

You know, so the, if we look at the DACRAs, There's petrolinatide. There's cagrelinatide. Those were kind of our benchmarks when we originally sort of designed the molecule. There's some additional molecules that have come out more recently. We think those are the right benchmarks for the DACRAs. And as a reminder, we have both DACRA and SARA, small molecules. But for the right benchmark for this, we think the DACRAs are the right benchmark.

Terence Flynn, Analyst — Morgan Stanley

And this is going to be a four-week or 12-week MADD study?

Raymond Stevens, CEO

Yeah, this will be a 12-week multiple ascending dose study with titration steps starting in the 1 to 2 milligram range.

Terence Flynn, Analyst — Morgan Stanley

And it's a four-week titration, I'm assuming?

Raymond Stevens, CEO

We can titrate roughly for half the time. And that's actually a really important sort of clarification point, Terrence, is because it is only 12 weeks, we can only titrate for half of that, six weeks. We can't do the titration steps once every four weeks. So this is an accelerated, you know, roughly once every one to two weeks titration steps. So that's an important distinction. If I think about our Aleniglipron program, when we went from our SAD study to our MAD study, six weeks was titrating, six weeks on maintenance. When we switched to our 36-week study, we were then able to switch to, you know, once every four weeks, which we know is the right point we want to get to. And we were also able to go to higher doses as well. So with Eleni Gliperon, SAD went to 90, we went to 120 in our 12-week, and then we went to 180, 240 at our 36-week. So we have a really good path for how we're going to execute the amylin program.

Terence Flynn, Analyst — Morgan Stanley

Do you think that you have enough time or you'll get up to doses where you can show equivalent efficacy to the injectable amylins and those benchmarks? Is that a fair comparison, just given some of those dynamics you walked through?

Raymond Stevens, CEO

Yeah, I think that we have to see. Again, I'm going to use the analogy with the Lennaglipron where we, you know, we only went to 120 milligrams in our MAD study 12 weeks because we could only titrate so much. In a 36-week, we could titrate in steps of four.

Terence Flynn, Analyst — Morgan Stanley

We had longer time. we could go to 180 and 240 where we've really seen where we've really been able to separate from the pack from everybody else having this full dose range opportunity okay and the other area obviously is combinations I mean I think that's the end game for most of these is you've got a glit backbone you add on another pathway whether it's an amylin a glucagon as everyone knows and so we've seen a lot of that in the injectable space obviously this is an oral now So it gives you that flexibility. So talk to us about what the combination strategy is and timelines for when we might see some. I know you guys have preclinical data, but timelines for clinical data.

Raymond Stevens, CEO

Yeah, so I view eleniglipuron in our amylin as monotherapies. And these, I think, are great monotherapies by themselves. We will be starting next quarter combination trials. Well, actually, we've already started in the MAD portion. we have an add-on arm where individuals that are stably on an injectable GLP-1, we give them 2671. And we're asking the question, do they have additional weight loss by giving them 2671? So I think that add-on that's already, so this is already part of the MAD study, is currently in progress. Next quarter, we'll combine two different oral molecules, and we'll look at GLP-1 plus amylin, and that's for increase in efficacy. And then we also have a GIP small molecule in our glucagon small molecules. We start to get into those combinations as well, as well as other non-incretin. We've always viewed this as life cycle management. Again, monotherapies, two different backbones. Those are molecules for the masses, for the large numbers of people. then the combos are more specialized molecules for different disease subtypes.

Terence Flynn, Analyst — Morgan Stanley

And so the MAD, you said some data, first half 27, is that going to include the injectable add-on data?

Raymond Stevens, CEO

That will include the injectable add-on data, correct.

Terence Flynn, Analyst — Morgan Stanley

And those people, I'm assuming, will have had to be stable on a GLP-1 for some certain amount of time.

Raymond Stevens, CEO

Stable on a GLP-1, you know, stable tolerability, everything. And then if you give them 2671, what is the effect?

Terence Flynn, Analyst — Morgan Stanley

And then what's the expectation for when we could see some data from an oral-oral, like a GLIP-AMILEN combo data for oral-oral?

Raymond Stevens, CEO

So the plan is right now to start that in Q4 next quarter, and then we'll have updates in 2027 on that program.

Terence Flynn, Analyst — Morgan Stanley

So probably second half is more likely. Okay, great. And then just remind us there, so you are for the GLIP, you're going to be using Eleni, is that right?

Raymond Stevens, CEO

We haven't updated on that. We have multiple molecules, GLP-1, just like we have multiple molecules for amylin.

Terence Flynn, Analyst — Morgan Stanley

Okay, so TBD. Okay, and then you mentioned this a few minutes ago, but DACRA versus SARA. So just give us an update in terms of how you're thinking about, you know, the pros and cons of both of those and then the timeline for your SARA.

Raymond Stevens, CEO

Yeah, we're very intrigued by the lower lintide data. We think it's very good data, and we're excited that ESAD, we're going to get an update of a lower lentide together with trisepatide, so that's going to be interesting to see. The way that we sort of look at this is, and it's why we're exploring bone health, you know, the difference between a Dacra and a Serra is calcitonin. You know, that's the simplest distinction. And with the Dacra, is there an opportunity there for bone health? So we view them as two different products is how we look at it. We don't look at it as an either-or. So we're developing both.

Terence Flynn, Analyst — Morgan Stanley

And kind of similar strategic question, like how do you think about maximizing value from the oral amylin program at this point? Like what are the next steps and how do you think about, again, retaining it further through development versus potentially partnering it?

Raymond Stevens, CEO

So at Structure, we're in the very fortunate position. We have a portfolio. We have our Phase III Eleni Gliperon. We've got our amylin 2671 that's now in Phase II, Phase IIa. and the other molecules as well and the combinations starting to sort of emerge. We know there's been a lot of interest in the emilin. It continues to be a very exciting space. We're going to see other data from other companies in the injectable peptides that's going to further validate and clarify the field. So we think that we're in a really good position. You know, your question about strategics, I think many have been, you know, looking forward to this data, and we were excited to release that data last week. We'll continue now with the MAD underway that will generate additional data. And we're going to stay laser-focused on execution for these while we continue dialogues with strategics.

Terence Flynn, Analyst — Morgan Stanley

And just that IP goes out with 2040s, I'd imagine?

Raymond Stevens, CEO

And we've been very, you know, the benefit, I think, of our platform, our name, Structure Therapeutics, structure-based drug discovery, by being able to visualize, see the binding pocket, we're able to really cast a wide net in terms of intellectual property, patenting of molecules. This clearly was an opportunity for us in the GLP-1 space with doing a deal, somebody having come to us to license molecules. Our amylin strategy is very similar. So I view this as we protect the castle, our main molecules, but we also create a moat to make sure, you know, we've made these molecules because we've been exploring the space, because we can visualize the binding site computationally. We want to make sure that we win in the space. And this gets to a common question I get, Terrence, you know, why do you have a second amylin going in? It's a different chemical scaffold. It's all about winning in this space.

Terence Flynn, Analyst — Morgan Stanley

Great. And just to remind us, you mentioned a GIP and a glucagon. And how long did it take you to get the amylin program, like, to lead into the clinic, all that kind of stuff? So as we think out for timelines for these other targets, like, is this three years, three years?

Raymond Stevens, CEO

Yeah, I'm sort of calculating in my head sort of, you know, we had the big breakthrough, I would say, in this whole space. You know, we had the big breakthrough in the Class B G-protein coupled receptors 2015. We got the structure of GLP-1 and glucagon. Those were the first two. It was 2018 that we got the three-dimensional structure using cryoelectron microscopy for the amylin receptor, and that was with different peptides that we were able to see. We made a decision a couple years ago that we saw the importance of amylin, and our GLP-1 program was well underway. So we basically shifted all the troops to focus just on amylin for a period of time. Um, I, I don't have the exact sort of answer in terms of timeline, but we put a heroic effort, um, which, which we continue on amylin again, to make sure that we win in that space. It did, it did come at a cost of us slowing down our GIP agonist program. Um, but that is now, you know, I think that is gotten some good steam and, you know, we hope to, you know, next year have some good updates on both GIP and glucagon.

Terence Flynn, Analyst — Morgan Stanley

So it sounds like the troops are back on GIP.

Raymond Stevens, CEO

We've been able to expand the troops. We've been able to recruit more troops. It's an army. We're at war. And so, you know, I would say we're expanding. We're not shifting.

Terence Flynn, Analyst — Morgan Stanley

Well, thanks so much, Ray. Always a pleasure. And best of luck. Thank you, Terrence.