Great. Thanks for joining us, everyone. I'm Terrence Flynn, the US Biopharma analyst here at Morgan Stanley. I'm very pleased to be hosting Structure Therapeutics. Joining us today from the company, we have the company's CEO, Dr. Raymond Stevens. Ray, thanks so much for being here. Just before we get started, for important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Ray, I thought I'd turn it over to you for some opening remarks before we go into questions. Thanks so much again.
Yeah. Thank you, Terrence, for having me here. At Structure Therapeutics, you know we started this company really focused on accessibility, you know making medicines that can be transformative, that can be made for the masses. At Structure Therapeutics, we're really focused on, right now, the GLP-1 area. We have three different programs. Our Eleni Glypron is our lead program, our oral GLP-1 small molecule that we believe to be potentially best in class oral GLP-1. We can talk more about this during the fireside chat. We have a data readout at the end of the year, both ACCESS and ACCESS II. Our oral amylin small molecule, as far as we know, this is the first oral amylin small molecule. That molecule is set to go into the clinic by the end of this year.
We think there'll be multiple sort of we're focusing on multiple oral amylin small molecules, both DAKRAs and SERAs. We're also very focused on combinability, you know being able to combine our oral amylin or our Eleni Glypron, our oral GLP-1, with other medicines, whether it's combining GLP-1 with amylin, GLP-1 with GIP, or our oral amylin with a PCSK9 or an SGLT2. We think you know this is really we think that we're one of the pioneers, one of the leading companies for oral small molecules in this very important space.
Great. Let's dive into a lot of that. I guess just at a first high level, you know a lot of focus on the obesity market and kind of the forward outlook. I think the way you know we model it is a 70/30 split, injectables versus orals. Eli Lilly has made some comments recently about their view of the oral opportunity. You guys are obviously investing in orals. Maybe just provide us with your latest outlook on how you see the market evolving when we do have more options, both in addition to what we have on the injectable side.
What's most important is patients are finally going to have options. This is really, really important. We know the injectables have really started the whole field, tremendous breakthrough medicines. I think it's going to be oral small molecules that are really going to expand it. The way that we look at this is what's really going to drive the market growth? Primary care physicians. Primary care physicians, what do they want? They want medicines. They largely sort of want oral pills that they can prescribe. The number one question we ask a lot of physicians as we think about our next-generation molecules, what do you help us design the next molecule? They say the number one thing that they want for their patients is flexibility.
They want to give their patients flexibility so that if they are feeling any GI side effects, they can reduce a dose, cut a dose in half. We think about all those things. In terms, Terrence, to your question, we view the market, patients are going to have options. We know the discontinuation rate of going from an injectable. Right now, the injectables are 50% after a year discontinuation rate. We think that's a really important market to address. Again, coming back to the primary care physicians, we see 70% of the market will be from primary care physicians. They will prefer the oral pill approach to at least start. As the field continues to evolve, we may see if they want more weight loss, they may decide that they want to switch over to an injectable. Those already on injectables may want to switch to an oral. Those are other opportunities that we see going forward.
OK, great. Maybe we'll talk about your lead asset, Elenaprevir, now an oral GLP-1 non-peptide, as you mentioned. The current option on the market from Novo is a peptide molecule. Maybe you could just provide us a view on your profile and some of the phase IIa data you've generated before we get into some questions around the upcoming data.
Our phase IIa data that we released would have been now about a year and a half ago. We announced in that phase IIa study, it was a 12-week study, a weekly titration where we go quite rapidly. We had 6.2% to 6.9% weight loss. We had low AE-related discontinuation rate, no safety issues at all. We’re very pleased. That really set the foundation for us to be able to sort of go into the phase IIb and to design the phase IIb. What it also showed us was 120 milligrams was really the maximum that we could go to in a 12-week study with weekly titrations. As we started thinking about our phase IIb, that's why we split it up and developed an ACCESS and an ACCESS II study, where the ACCESS study is focused on 120 milligram dose.
The ACCESS II allows us to go up to even higher dose to potentially see even more efficacy. We’ll go up to 180 and 240 milligram dose.
Yeah. The duration there, those are 36-week studies, right?
Correct. That's correct.
Maybe just remind us the titration. I know there's some differences in terms of the titration versus you mentioned you're doing pretty rapid titration in the first study. How does that change in the IIb?
Yeah. When you have a 12-week study, you only have roughly six weeks that you can really titrate up, and then you have six weeks for being on the maintenance dose. You do have a very rapid titration. What we've also learned from the peptide field is titrations work best for this class of medicines really roughly every four weeks in titration steps. Peptides have shown us this again and again and again. As we look at orforglipron, they've done the weekly titration in a 12-week study, 36-week. They went to once every two weeks to once every three weeks. When they went to phase III, they went to once every four weeks. What we decided to do in our phase IIb was to go straight to once every four-week titration step. We think that's what the body really needs to adjust.
We think this titration scheme is really the right solution, part of the solution for addressing tolerability.
What are the specifics on timing? Are you going to release both of these at the same time? Is it a sequential readout? How are you thinking about the timing of those readouts?
Both ACCESS and ACCESS II studies will read out at the same exact time at the end of the year, 36-week studies. We're looking forward to that towards the end of the year.
Can you give us, is it this like December readout, January? Is it?
I get that question from investors all the time. They want to know what is the exact sort of date. What we're guiding everybody towards is the end of the year.
End of the year. OK. All right. Fair enough. How about the amount of data in the press release? I know there's oftentimes a lot of debate about how much you can present versus having to withhold for a medical conference. Maybe just walk us through current plans in terms of how much data is going to be in the actual press release.
Yeah. We will be releasing, obviously, the efficacy data. Everybody will be looking for that data. We will also release the tolerability data and, very importantly, the safety data.
OK. On the estimates, is this one where you'd have both of those estimates in there? How do you think about that?
We will be reporting the top-line data and the primary estimate.
OK. Got it. OK, great. I guess the other question we get a lot, and I know you probably got this a lot today, is just the benchmarking data. We look at orforglipron. There are some changes made phase II to phase III. As we benchmark your data, what's the best data set that we should look to? I think in phase II, they had a 36-week study, showed like 9% to 15% roughly. Placebo lost 2% or something. Is that a fair comparison as we think about cross-trial comparisons?
Yeah. The usual caveat, cross-trial comparisons are difficult. We think that the right benchmark is 36 milligrams at 36 weeks, so really easy to sort of remember that 36, 36. There are really two data points there. We think in terms of efficacy, we have the phase IIb study from orforglipron at 36 weeks, so that's sort of one number. We will see next week at EASD, September 17. We're looking forward to seeing that number. We'll get a chance to see the 72-week data. We will, like most people, look at the curve and draw a line from 36 weeks and see what is that number. In many ways, we think the phase III data is a better comparison on efficacy because it's the same titration scheme, once every four weeks. They're also on maintenance dose the same period of time as our Elenaprevir.
We think that's really the right benchmark for efficacy. We're saying it should be a range, both the phase II data, 36 weeks, 36 milligrams, and the phase III, taking that cut. It's more challenging to do that in tolerability. The reason for that is in the phase IIb, they had a much more rapid titration, this once every two to three weeks. That's why I think they saw sort of the higher efficacy. With the four-week titration, we're not going to get a cut in the phase III data. We're not going to get that cut at 36 weeks. We really just get the top-line data at the end. We will see the time course. They typically present that data, how tolerability changes over time. We see most of the events happen at the beginning, and then it gradually comes down.
That's going to be a little bit more difficult. We think the right comparison is probably the phase IIb, where we have the full data set of 36 milligrams at 36 weeks. The one other variable that does come into play is with orforglipron, as they in their phase IIb, going to their phase III, not only did they extend the titration, but they actually also came down in dose. Our goal in a phase II study is really to find the upper, what is the dose, how high can we go in dose? We know when we go to phase III, we always come down in dose. That's one more variable that we can, as we think about phase III, we have that opportunity to go down in dose. We're really looking for the upper dose limit.
Yeah. If I look at their phase II, the orforglipron discontinuation rate, it looks like due to AEs, I think it was 10% to 17%. That's kind of the range, I guess, what you're saying. Don't look at phase III because that was a longer study. If we look at their phase II, again, it was 10% to 17%.
I think that in the phase IIb study, they had two different at the 36 milligrams, they had both a once every two-week titration and once every three-week titration. I think the numbers are 10% to 21%, the numbers that I recall. We think that it should be in that range.
OK. Great. I think the other thing that you guys announced relatively recently was an extension on ACCESS II. I think you've talked about the titration period, you're ramping up, and you won't be at the top dose for a long enough time. As a result, you added on another, I believe, eight weeks onto the back end of that study. Maybe just talk to us about setting expectations for ACCESS II, given that dynamic that you're still in the ramp, and patients aren't going to be at the higher target dose for the same period of time. It's not truly like 36 weeks, I guess.
OK. There were two different announcements that we made. First of all, we did announce an open label extension on the ACCESS study. That's really being driven by the challenges, including the placebo group. In these studies, you know that you're in the placebo group within the first four to eight weeks because you're not seeing the sort of weight loss. We think this is something that the whole field continues to sort of work on. We decided to add that open label extension for those individuals that are in the trial. They could get access to it in an open label extension. In the ACCESS II, those are two different studies where we're looking at 180 milligrams and 240 milligrams. We're hoping to see that increase potential in efficacy. What we're really looking for are two things. One, are there tolerability changes as we go to 180 and 240?
An individual has been on 120 milligrams. As they go up in dose, do we see a change? That's something that we just announced last week that our IDMC has met. They've approved us going up to 180 and 240 based on what they've seen from safety, both on target and off target. That's one of the goals. In terms of efficacy, we're really looking still toward directionality. The question that we're asking is, should we go to 180 and 240 in the phase III? If we see directionality changes, improvements in efficacy, then that'll give us the confidence to increase the dose in the phase III study.
You're saying up to 180 and 240.
We're doing 180 and 240. We'll be at 180 for eight weeks and 240 at four weeks. With this extension, it gives us an additional eight weeks. Because we have the extra time, we decided to take that time to give us added information so that we could answer that question as best possible for the phase III.
Will we get, when you guys put out the data, those curves so we can look at how this slope compares for those higher doses?
What we'll be reporting on is, again, the efficacy, the top-line data. The top line will be the top line. The curves will probably sort of reserve that for a future meeting. We'll give obviously all the efficacy numbers, the tolerability numbers, and the safety numbers.
OK, great. Maybe the other thing, I think, maybe just speak to what this implies for the safety, tolerability of the program as a whole if you guys are going forward with these open label extensions. You also announced another series of trials. What's the other takeaway in terms of the, I guess, big picture of safety of Eleni Glypron here?
Yeah. We did announce that we have three additional studies coming on, two of which actually have already started in Q3. We have what we call the switch study or maintenance. The question that we're asking here is, if you're on an injectable and you want to switch over to an oral, can you go at a sort of same high dose? Or do you have to retitrate and start over again? We don't know the answer to that. We want to do that as part of the sort of switch study. That's being done. Again, with the increasing confidence of Elenaprevir, and again, we think we have potentially best in class now that we've seen all of the orforglipron data, you know that's an important question to ask. The second study that we announced was a body composition study.
You know the old mantra, never ask a question in phase III that you haven't pretested before. We want to add that body composition study. That's the second study. That's a 40-week study. The third study is a type 2 diabetes. We've gone in type 2 diabetes, overweight, up to 90 milligrams. We have not gone to 120 milligrams or 180 and 240. We want the label to be as broad as possible. We don't want to exclude individuals living with type 2 diabetes. Many of them, 90%, are overweight. By doing this diabetes study at the higher dose, it'll allow us to, it'll inform us to design the phase III appropriately so we can have the broadest label possible.
OK, great. Before you go to the phase III program, I just wanted to ask one I forgot to ask is the baseline characteristics of your study. Maybe just remind us, phase IIa to phase IIb, any baseline characteristic differences for your study? When we're making these cross-trial comparisons to the Lilly orforglipron data, anything that you'd call out high level that we should be mindful of when we make these? I know sometimes it's baseline BMI can matter, geography can matter in terms of tolerability sometimes. What other things should we be mindful of when we make these kind of comparisons?
Yeah. Both ACCESS and ACCESS II are both being done 100% in the U.S. The baseline characteristics will be similar to other 36-week studies. We do tend to go with higher BMI. The question that we're really asking is, you know what can the drug do? You know how well can the drug work? We really want to test it in that higher BMI population. We look at that. With the demographics, what we look at is what is the demographics of the U.S., the U.S. study. We try to align that to the U.S. census numbers.
In these obesity studies, historically, there's actually been more females than males that are involved. Is that what we should expect as well?
Yes.
OK, great. On the phase III program here, maybe just high-level thoughts on kind of, you know, design, scope, comparator arm. I mean, those are all the questions I think people are focused on, partly because of, you know, what you noted. There are other options out there now for patients. How do you kind of design the program but also manage the reality that, you know, if there are patients on placebo that are not seeing the weight loss, then, you know, there are other options available to them? How are you thinking about navigating that environment?
The FDA in January gave really good clarity as to chronic weight management studies. It's the first update since 2007. As part of that update, 4,500 participants, 1,500 on placebo. We have clarity of that. No cardiovascular outcome study required. That was also, I think, good news. It really highlights the FDA is looking at obesity as a pandemic. It's a real problem that needs to be solved. You know they're trying to see more of these medicines get developed and get to market as fast as possible. We have no cardiovascular outcome study requirement. All that we're doing, all the phase III preparation work right now, readiness, that's all underway. That includes these additional studies that we have ongoing. We're doing all the prep work there. The placebo group, I think that this is a growing challenge that the whole field in general is seeing.
We have to consider this. Part of the reason we're doing the open label extension on our phase IIb is to learn from that and how that can help guide us as to how best to do the phase III clinical trial.
Yeah. One other thing that I think has been coming up is, you know, there's this announcement with the FDA Commissioner Priority Review Voucher program, this new program. Is that something that you guys are thinking about at all, or are you considering? I think it definitely gets speculated that maybe there could be obesity drugs that could go down that path. I know you guys aren't there yet, but it seems to me like another iteration of the Breakthrough Therapy Designation Program. Any thoughts on that?
Yeah. If thinking about oral small molecules, GLP-1s, there is a lot of tailwind that we've had in 2025, tremendous tailwinds. I include the orforglipron data as part of those tailwinds. We see the WHO has now included GLP-1s, which I think is an important step, the priority voucher. The new FDA guidance was, I think, a really good step forward to defining what's needed to address the obesity pandemic. I think all of these tools and all these changes, you know, there's a lot of frustration in the field and drug discovery in many different fields. I think in the field of obesity, recognizing the pandemic's sort of status, nature, recognize the problem, and recognizing there are some solutions. They need to be developed as efficiently as possible and to give the patients as many options as possible.
These are all tailwinds that we're fortunate in today's age, we're fortunate to be able to ride on.
Maybe the last one before we go to the rest of the pipeline is just thoughts on a potential partnership collaboration here. Obviously, the data is an important card to turn over. How do you think about this? Obviously, a phase III program is going to be pretty broad in scale when you think about the different, you know, beyond just chronic weight management. You're talking about, you know, diseases like OSA, chronic kidney disease, these kind of things. How do you think about partnership collaboration?
Yeah. Right now, at Structure Therapeutics, we are laser-focused on the data at the end of the year. At the end of the day, data speaks. Data is going to tell everything. Yeah, so that's where, at Structure Therapeutics, that's where our head is at. We also know that we have to do a lot of phase III preparation work. We're making sure that Elenaprevir is as prepared as possible for those phase III studies. We continue to have dialogue with many different strategics, and we'll continue having those dialogues. We're laser-focused on that. Coming back to your question about there is so much opportunity. Again, with the FDA, the guidelines are very clear in chronic weight management, and we feel comfortable doing a chronic weight management phase III. What we cannot do is eight more phase IIIs.
We would like to have a strategic to really help us expand the number of different indications that Elenaprevir can go into. Most importantly to us, what really drives us at Structure Therapeutics is accessibility. We want to be measured by the number of people that get access to these medicines, and these medicines help. We believe having a commercial partner is really, really important. That's something that we prioritize.
Yeah. Maybe I'll sneak another one in, just the scalability. I think you know we had kind of alluded to this earlier. You guys are non-peptide versus peptide, so maybe just remind us why that's important, what that means in terms of scalability and scope. Obviously, there were some challenges last year on the injectable side in terms of capacity. Why is scalability important, and how do you think about that from an Elenaprevir standpoint?
The peptides have been breakthroughs. They've really established, created the field itself. I think that's been tremendous. Small molecules, I think, really will expand. The reason for that is, with the peptides, we've seen minus change of sales, if you look at the script data, has been somewhere around 5 million. We don't know the compounding numbers. From Eli Lilly and Novo Nordisk, it's been in that sort of 5 million range. It'll grow to sort of 10. We know in the United States alone, the need is 100 million. The estimate's by 2030, it'll be 25 to 30 million will be on this class of drugs. How do you meet that challenge? With small molecules, right now today at Structure Therapeutics, we have the ability to make 6,000 metric tons. What exactly does that mean in terms of patients?
We can make enough material today to supply the needs of 100 million patients at a 120 milligram dose. Small molecules, traditionally, they've always been the solution for making a medicine at scale for the masses. I think that small molecules, and Elenaprevir included in this, it's really a medicine that's been made for the masses to really hit that. I think about we just talked about U.S. numbers. I really worry about the global numbers. The estimates are by 2030, 1.3 billion people will be overweight or obese. This is, again, a growing pandemic. How do we fit the needs for that? One of the things that I hope changes as we continue this dialogue in this field is we transition from focusing on a specific weight loss number to focusing on how can we really help all the people that need these medicines.
I think that's where the oral small molecules, they really have that potential. The reason why I like the orforglipron data that we know that we've seen this summer is it's a molecule that can be made for the masses. 70% of people need 10% weight loss. They don't need 25% weight loss. I think that, that's where at Structure Therapeutics, we're focused, both in terms of having a potentially best-in-class oral GLP-1 with Elenaprevir, but also importantly, the combinability. To the last point of small molecules versus the peptides, small molecules give us that ability to combine, whether we're trying to combine it with our oral amylin, with our oral GLP-1 Elenaprevir, or combining with a PCSK9 or an SGLT2 with our GLP-1. We have that ability for combinability to really do all that for lifecycle management and product evolution.
Great. That's a good segue to your next asset, which is GSBR-2671, your oral amylin, which you talked about a little bit at the beginning here. Maybe just remind us why amylin is interesting. Why are so many companies focused on amylin? From your profile, what are you trying to deliver? We've seen some data now from some of the injectable amylins. Novo had some data for their cagrilintide. Eli Lilly had a loraglutide. We haven't seen anything from oral, obviously, yet. You are going to be one of the first there. What's the kind of target profile? Why is amylin interesting? What's the target profile that you hope you can deliver in the clinic?
First, the reason there's a lot of interest in amylin is, is there the potential that it can be more tolerable than the GLP-1s and selective weight loss as well? There's been this discussion between selective fat loss versus muscle loss. These are the two things that are being probed in studying this. There's right now a number of different molecules. We call them both DAKRAs, dual amylin calcitonin receptor agonists, and SERAs, selective amylin receptor agonists. I'm often asked the question, which is better? We started out working on a DAKRA. We use kaglilinotide as kind of our benchmark to try to achieve that. Our first molecule, GSBR-2671, is a DAKRA, a one-to-one ratio between amylin and calcitonin. The preliminary data that we have today in preclinical studies looks really encouraging. We also like the data that Novo Nordisk has shared on kaglilinotide. It's been in a large population.
It's a safe molecule. We know this mechanism is safe. We like that. We like the decrease, the improvement in tolerability have also been shown. We also like petrolinotide from Zealand. We're watching very carefully. Olorilinotide is a more selective molecule for amylin. At ADA this summer, we were intrigued by that data. What we're trying to do with the oral small molecule, same thing that we did with the GLP-1s and same target product profile as well. We want to see, we want to develop an oral once-a-day small molecule medicine that can be made for the masses with this thesis that it may have potentially better selectivity on weight loss and a better tolerability profile. We see GSBR-2671, our oral amylin, first-generation molecule, as a potential for monotherapy. We also like the, we think about the combinability as well.
What can you say about once a day versus twice a day at this point? Any insights there?
Yeah. One of the things that's really important is from the target product profile, we believe it needs to be a once-a-day drug. We think about, you know, there's often a question about the PK parameters, half-life. What we ask ourselves is, we're really driven by where's the efficacy coming from, AUC. We care about the C trough. You know, what is the exposure in 24 hours to make sure that it is truly a once-a-day drug? We monitor that very carefully. We care about that. We'll use the same exact parameters that we use with GLP-1, with amylin, to make sure that we have coverage at 24 hours. It is a once-a-day dosed drug.
Great. Maybe the last one on this topic is just that as you think about the next step after a phase I, would you pursue both mono and combo? Obviously, you can do that internally. You could go an oral with an injectable. How would you think about the scope of opportunities for a phase II program, just given there's so many different options?
Yeah. There is, and I'm glad you used that, there's a lot of different options. Again, we view our amylin both as a monotherapy for moderate weight loss. One of the big questions we always ask physicians, again, about the next-generation molecule, they say, you know, we want good weight loss, but we really care about tolerability. With that as a driver, we think about the amylin profile as a monotherapy. If you want more significant weight loss, we've already seen by combining these two mechanisms, we can have that combination. We can have that increase in weight loss. We see our Elenaprevir together with GSBR-2671. We've done a lot of preclinical studies. We just had a poster presentation at ADA this past summer, showing that synergistic complementary sort of effect there. We see it in combination.
Not to forget, we also have the GIP and the other molecules, small molecules, where we can also do combinability to give us even more enhanced effects.
What is the timeline on those other targets, GIP, those ones? How far out are we from getting one of those to a lead?
Yeah. We have leads for all of them already. We really prioritized amylin, given the opportunity that we're seeing. Don't be surprised if we announce another DC for amylin. We think being the first mover in this space is important both to increase our probability of success. We will put multiple amylins into the clinic. We think that's really important. Multiple chemical scaffolds will also put both a DAKRA and a SERA, as we were talking about before, into the clinic. We really want to sort of place multiple bets in the amylin space. We also think about the, again, the combinability aspect of it. GSBR-2671 will go into the clinic at the end of this year. Again, don't be surprised if we announce another DC on amylin. GIP, GCG, glucagon, we continue to process those. We've just really up-prioritized amylin, given the data that we have to date.
OK, great. Maybe I'll just turn it over to you to wrap up here for us, Ray. Anything you want to leave us with as we think about the forward, obviously a very busy time for the company.
I think in closing comments, obesity is a pandemic. Patients need options. Patients really need options. I think oral small molecule pills really will be part of the solution that will help the world community. I think this is a really important aspect. At Structure Therapeutics, we've really tried to focus on accessibility. Again, making molecules that are available to large populations, we think that's the right place for us to focus. I'm most excited about the whole field in general having these different options and progressing these medicines to really get them to the patients and the physicians who are all waiting.
Great. Thank you so much, Ray. Pleasure having you here, and best of luck.
Absolutely. Thank you, Terrence.
Thank you.
Thank you.
Thank you.