Well, good morning, everyone. Thanks for joining us here at the Goldman Sachs Healthcare Conference. They're able to be joined on stage today by the team from Structure Therapeutics. And it's been a really busy week with respect to obesity. So I would love to actually open up there. We're coming on the back of ADA. What did you learn over the weekend, and how does that kind of inform your view of the obesity landscape as it stands today?
So, one, we had a great ADA just coming from New Orleans. Dr. Julia Rosenstock gave the opening lecture with our data, our access data. And, you know, I think what we sort of took home from that, you know, we also had a Nature of Medicine publication that came out simultaneously to the presentation on Friday of ADA. We clearly, coming out of ADA, we clearly have the best-in-class profile. We just saw data from AstraZeneca come out yesterday. and that was one of the pieces that I think the field was waiting to see. There's a tight grouping, I think, of the oral pills down in that sort of 11% to 12% range, and we've currently shown data up to 16%, so we're feeling really good about that. The other piece, I think, from ADA that was also, I think, a highlight was the amylin progress. There's a whole symposia on Friday late afternoon on amylin, And then we released data, a presentation on Sunday, showing some additional data on our ACCG 2671 on the amylin that has a very different profile than our Eleni gliperon. And the main thing that's different is it has a 60-hour half-life in non-human primates, so likely to be longer in humans. So excited about that, and we'll release that phase one data next quarter.
Amazing.
A lot of news from ADA.
A lot of news. Let's stay at kind of like the high-level obesity market landscape. I would love if you could talk a little bit about your philosophy on where the obesity market is going over the next, let's call it five to ten years, recognizing we're in the midst of a lot of change right now. And I would just love if you could kind of talk about the direction of travel for the market.
Yeah, Corinne. So if you actually just go back six months, let's go back to December. Is there room for oral pills? No, people are sort of still debating. They're like, injectables are fine. Injectables are actually the convenience of once a week and everything. Fast forward only one month or a Wagovi launch. It is the fastest launch. Five months later, you know, now 14% of the market is already oral pills. And this is all growth. 80% of it is growth. And so I think the oral pill market is, and now we have Fundeo, and they're really starting to advertise. So I think the oral pill market is just going to continue to grow the field, and that's a really good thing. It's all about giving patients options at the end of the day. And there was all this pent-up demand for oral pills. So I think that's sort of one place where it's going to continue to grow. I think the other area that we're going to continue to see is patient segmentation and And combinations are going to be really important in terms of patient segmentation. So we're excited. We'll start our phase 2A for amylin next quarter. And then we'll start our combination of our GLP-1 with our amylin in fourth quarter. We're seeing more and more of these combos for specialized markets, you know, a combo of GLP-1 with glucagon for liver disease, a combo for, you know, you can imagine a PCSK9 or an SGLT2. So we're going to see five to 10 years. Combos are going to become more and more important. but the foundation molecules, the GLP-1, our oleniglipuron, our amylin, those monotherapies, they're really for the masses, the large numbers.
And maybe you could also talk about the direction of travel for pricing as that's been a key area of focus as these new drugs have come to market.
Yeah, June, you're the money guy. Yeah, so, you know, this is a rapidly evolving space, as you can imagine, and price has been coming down. But the opportunity for us on small molecules is cost of goods are really low, right, where cost of goods are going to be traditionally where small molecules are, and that gives us a real big advantage with respect to pricing. It's going to be different for oral peptides because their cost of goods are just going to be much higher and they're going to need more dosing to get the same level of efficacy on top of the fact that they got it formulated as an oral in order to work as a peptide.
All right, with those kind of big pieces in mind, Maybe we could talk about your individual programs. So starting with Alina Glipra, and you have demonstrated Phase II efficacy across a couple of studies now, maybe you could just walk through the highlights from that program and compare now versus a broader set of oral obesity medications, as you mentioned, AstroData earlier this week.
Yeah, so we shared back in December, it was ACCESS and ACCESS-2 data. So ACCESS went to 120 milligrams, and ACCESS-2 went to 180 and 240 milligrams. So what we've seen between the December data release and the March data release is we've seen up to 16% with no signs of plateauing. So again, best in class profile in terms of efficacy. What we've also shown is, you know, keep in mind in phase two, it's there to really explore. And so we know that we do not want to start at five milligrams. We do see, you know, some tolerability challenges. When we go to 2.5 milligrams, we see the tolerability significantly improves. So, again, our starting dose in Phase III is going to be 2.5 milligrams. So that's another sort of learning that we've had. We've also done, I think we've done more Phase IIs than even the big pharmas. And one of the reasons why I sort of point that out is we've really figured out how to work with helenoglipiron. So the 2.5 milligrams start, the once-every-four-week titration step, we have additional studies going on in body composition, for example. How exactly do we do those studies in the Phase III setting? And then what is the maximum dose that we want to go to? Again, we've tested up to 240 milligrams. We've had our end of phase two meeting with the FDA. And so, you know, we'll be released. We'll start the phase three in Q3, and we'll update further on exactly the doses. But we've really learned a lot from this. That's really put us in a good position to start phase three.
Okay, great. Well, that's a great segue to the alignment you have reached with the FDA end of phase three program. Maybe up top, like what are the key features of that phase three program as you kind of see it?
So, you know, the FDA, you know, there's lots of turmoil at the FDA. We're all familiar with what's going on there. But in this particular space, obesity, we've had a really good set of interactions. You know, they're clearly very, you know, they're worried about obesity in the United States. Seventy percent plus of Americans are overweight, 46 percent are obese. And so they came out with new guidelines last January, January 2025. And in those guidelines, they were very specific. You know, it needs to be 52 weeks on maintenance dose after your titration phase. It needs to be 4,500 participants, 3,000 on drug, 1,500 on placebo. They highlighted maintenance. You know, they're really, really worried. You know, 85% of people discontinue injectables after two years, 60% after one year. So they're really worried about what's referred to as the yo-yo effect. People lose weight, and then they gain weight. Lose weight, gain weight. So they highlighted maintenance. I think this is where small molecule pills are really going to have a particularly important fill-up unmet need for long-term maintenance. So with all those guidelines, you know, one question we get is, you know, would a strategic do anything different than what we're doing in our phase three? The answer is no. You know, strategics, they have the same guidelines from the FDA. We've already seen in the other designs that others have done. So for chronic weight management, and I'm specifying chronic weight management phase three, it's pretty much really dialed in by what the FDA has guided everybody towards. So it's very straightforward.
Okay. In terms of the titration schedules and top doses you're taking forward, I know you've kind of figured this out internally. What should we know about how many schedules you're taking forward, how long it will take to get to the phase or to the top dose, that kind of thing.
So what we've disclosed so far is that we are going to start at 2.5 milligrams. Why 2.5 milligrams for us is a sort of sweet spot is, you know, for sort of two reasons. One, the tolerability profile improved significantly when we started 2.5 milligrams, so it was a really big learning. Second, 2.5 milligrams is really, we can see some weight loss. It's really important. And so you may be familiar with what's going on with the placebo arm in these Phase III trials now. You know if you're on placebo within four to six weeks. If you're not losing weight, if you're not having any of the sort of the GI AEs, you know. And keeping people on the trial is a real challenge. So we've had a lot of learnings from the Phase II studies on how to keep people in placebo arm on the trial for Phase III. But 2.5 milligrams is the right start. You lose a little bit of weight so that you know that you're on drug. And then the sort of stepwise four-week titration steps. We haven't disclosed the titration scheme yet. We'll disclose that when we start the phase three. And it really depends. We'll be using three doses, sort of a low, medium, and high dose is what we're going to sort of do. And, you know, I'm really excited to sort of get that started.
How did you think about what would be patient-friendly with respect to titration schedule in terms of how long it takes to kind of get to the highest doses?
Yeah, so one of the things I should have mentioned at the very beginning was, so with the data release that we had on Friday at ADA, we also released simultaneously a paper in Nature Medicine. And in Nature Medicine, Dr. Blykohol, our CMO, came up with this idea of using heat maps. So basically what we've disclosed, I think it's most data anybody's disclosed, individual patient data of what exactly is the journey and dose by dose for that access study. And then one of the questions that we were asking was, if a patient skips a dose, what happens? Do they have to start to re-titrate? If a person has a GIAE, do they have to sort of restart or go down? And sort of, what exactly is it? And what we learned from this heat map, so it's in that paper, it's also in our updated corporate deck, is individuals skip doses all the time, and they don't have any problem, absolutely no problem at all. and life happens. You forget something, you know, you travel and you forget to sort of bring the pills. So that was a really important finding from that access study and that nature medicine paper came out with those heat maps. So I hope that people start to include these. The cumulative AE tables that we get, you know, if I ask you it's not fair to ask you this right now, but over the past nine months, have you been nauseous? You know, I think almost everybody would say, yeah, in the past nine months have probably been nauseous once. So these numbers, it's what everybody reports. But I think these heat maps of individual patient journeys really tell what's going on with the patient. And what they do, everybody modifies the titration. I mean, this is personalized medicine at a global scale. Most people don't even go, if I think about ZepBound, I only know two people that have gone to the 15 milligram dose. Almost everybody that I know at least has gone to 10 milligrams at the max. And so we really want to give patients the flexibility to titrate kind of on their own schedule. The clinical trial will try to be relatively, you know, organized on it, but we do allow down titration. We do allow holding titration. It's really up to the individual. What's most important is that they have a good patient experience and they follow a titration scheme that they're comfortable with. And when we were doing our own research on this five years ago, I remember going to a clinic outside of Boston, outside of 128, and we asked the physician, what do you want the most in next-generation obesity medicines? She was very clear. She said, look, my phone is ringing nonstop. I don't want my phone sort of ringing nonstop. I need flexibility. I need to be able to give my patients simple instructions. I need to give them flexibility. So if they want to cut a pill in half, if they want to, you know, hold a titration up and down, I need to give them that flexibility. And that's the way we try to design the drug.
You mentioned the trial conduct challenges, particularly with respect to discontinuations across both placebo and treatment arms, largely because people know they're not on drug, and they could go get the drug from many, many options. So, I guess, could you be more specific about what you've learned and how you plan to manage that into phase three?
Yeah, so one of the experiments, again, you know, what Bly did in the trial design for AXIS is he added in, And again, the heat maps were really creative, innovative. What Bly also did in the access study was he did an open-label extension. And what exactly that was was after nine months, we gave participants the option, would you like to go on drug for another nine months? And what was remarkable was 86% of people signed up for the open-label extension. That includes a placebo arm. So people don't want to stay on the placebo arm for another nine months. We gave them the ability after nine months that they could go on, and they would start at 2.5 milligrams. So that was really important to give them. So part of our solution on the placebo arm with these clinical trials is giving people the, you know, knowing, okay, I'm on the placebo arm. I get drug after, you know, the end of the initial period. And then they're going to be on drug. They're going to get sort of the care and everything, the health care. that is an incentive for them to agree, you know, to conduct the trial appropriately and to follow the guidelines. Because we know, we just saw data last, you know, this weekend at ADA, there were placebo groups in some of the clinical trials where a significant number of participants on placebo were getting compounded GLP-1s. They had a 5% weight loss in the placebo arm. And the participants, they asked them, did you take a GLP-1 during the trial?
and they said yes. Great. Okay, so you talked about the weight management studies and those being very similar across the board, whether it's being conducted by a large or small biotech, but I guess as you think about the adjacent indications and testing other long-term health outcomes, which we've seen many of these programs do, how are you thinking about a broader phase three program, and what is your capacity to kind of execute beyond the weight management
trials. Yeah, we feel, we actually feel very confident we can do a phase three in chronic weight management, you know, based on our experience as good as anybody else. So, you know, we've really learned that. But our experience, our expertise does not go beyond that. You know, we cannot do a liver sort of parallel phase three in liver disease, MASH. We cannot do one in heart failure. This is outside of the scope of what we can do. But chronic weight management really is the fundamental, it is the foundation in this field. It's all about sort of losing weight first. And so, you know, that's where we're focused. And where, you know, the natural question where this sort of goes to is, you know, where does a strategic partner sort of fit in? A strategic really has that ability to go into other disease indications. And so we continue having those,
you know, those conversations. Okay. As you think about and you're having those conversations, I imagine it does come up, like what adjacent indications would be the best fit for a product with this profile, I guess, what would you share in terms of the adjacencies that you think Alenoglipron would be best positioned to serve? Yeah, June, you've had a... Yeah, I mean, in terms
of phase three, and we're seeing this with other programs like Orphaglipron and other competitors, they're in type 2 diabetes, they're in fatty liver disease, they're in osteoarthritis and sleep apnea, right? So these are all adjacent indications that can be pursued, and with a strategic, we can expand into those indications. But as Ray said, you know, our focus is chronic weight management. We have the funds to be able to do that. We have the experience and the learnings to be able to do that. We've got the green light from the FDA to start that phase three and we can deliver that data and, you know, by the end of 2028. So to put a finer point on it, when do you
think you would be able to start a phase three program here in terms of timing through the rest
of the year? Yeah, so we're guiding to the third quarter. Right. And, you know, it was just last month that we provided an update with respect to the end of phase two. Again, green light. We're aligned with the FDA on what that phase three needs to look like. And when we start that phase three in the third quarter, we'll provide an update with respect to the doses. You already understand the two and a half make start low, go slow four week titration strategy. And the only remaining item is really the three doses that will provide an update, and we have that alignment
with FDA on. One somewhat adjacency is the kind of maintenance area, and you talked about it earlier. Just remind us the parameters of your maintenance switch study from weekly injectables, and what do you think the benchmarks are for weight loss and management in that kind of
indication? Yeah, so we have right now, we have another trial going on right now that we call maintenance switch, and really the sort of question, the scientific question that we're asking here is, do you need to, when you want to switch over again, we know the discontinuation rates in injectables is significant. It's a significant issue. And so do you have to re-titrate if you want to switch over to an once a day oral pill for long-term maintenance? Or can you seamlessly go from one dose of an injectable straight over to an equivalent dose of an oral pill? So that's a scientific question. Our hypothesis is that you should be able to seamlessly go over and maintain that sort of weight loss. That's the hypothesis. Once your body has adapted to this class of medicines, we don't think it's a molecule-to-molecule specific thing. It's really about you've modified your eating habits, smaller portions. Your gastric emptying has sort of, you know, regulated. Even the, you know, sort of effects of, you know, food noise and everything have sort of settled down. So this is the biological hypothesis, being able to go over seamlessly to the same dose of an oral, but we need to do this experiment. So we're doing that right now. That will read out in Q4, and that will set the stage. You know, we think that this is part of a significant go-to-market strategy of how exactly do we sort of enter the market, and switching from injectables over to orals is one of several different paths.
Would you think about a registrational program, like with that kind of setting or cohort of patients, and is that as well-defined in terms of what it would need to look like?
I'd say let's stay tuned on that. You know, right now what we're laser-focused on is there is the foundational. The FDA has their requirements that we have to meet. So that's what we're sort of focused on, and that is the sort of longest study. Again, the 52 weeks on maintenance, that's defined by the FDA. These additional studies are a subset of that, and so you can imagine a series of Phase 3Bs.
Okay, perfect. and you did mention that you have the funds sufficient to complete a phase three weight management program but could you be a little bit more explicit about what that kind of cost you
anticipate being? Yeah I mean it's going to be a pretty typical you know phase three it's 4,500 patients and and it's going to be in the range of you know 300 to 500 million right we have a billion and a half in the bank and we will be able to to complete that registrational phase three
study. Okay, great. Maybe let's talk about ACG2671 or the amylin program that you referenced earlier. Maybe start with just the data you shared at ADA. What do you think people should be most excited about or take away from the post you presented? I think, so first, this is a
non-human primate, so I just want to sort of set that. It's still a preclinical sort of model. We have a phase one going on right now. That'll read out next quarter. So that's a human single ascending dose, SAD sort of study, the data that we shared was we see significant weight loss both as a monotherapy and in combination with GLP-1. So that was sort of one, you know, one important thing. Non-human primates in this class of medicines really is the best animal to study in terms of, you know, human. So that was, I think, sort of really good to see. The second thing is, you know, we got additional PK data. In particular, one of the things that's been a topic of conversation, the half-life is in non-human primates, more than 60 hours, 6-0. And so typically in humans, you will see an even longer sort of half-life. This opens up real differentiated profile. Eleniglipuron clearly dosed once a day. We saw best-in-class efficacy. So the eight-hour half-life, you know, is not an issue. But this opens up additional sort of dosing sort of regimens that I think, again, will create a potentially differentiated profile. So, you know, that was, you know, got lots of questions, had lots of really good conversations. And then what it also does is it sets the stage. You know, I think of structure has been traditionally, most of our value is really in Aleniglipuron. We haven't gotten a lot of credit for Amlin itself. And it's still a little bit early on Amlin once we release the human data. That's more in particular the proof of concept. But we also, in Q4, we'll go into human trials for the combo, and that's our GLP-1 plus our amylin. And, you know, to me, so we're going to go from a one-product company to a three-product company, you know, in the second half of this year.
Maybe one of the things you mentioned earlier was that there was a symposium on amylin at ADI. I guess as you think about the role that amylin, but particularly oral amylin, could play in the market. Could you just contextualize that for us?
I think the rules are going to be very similar to the GLP-1 space. Is there a market? And this was a question just six months ago, end of 2025. Is there really a market for oral GLP-1 pills? Clearly, the answer is 14% of the market in five months, 3 million pent-up demand, 80% growth of the market. Clearly, there is a large market for oral pills. It's going to be the same with amylin. And in amylin, the hypothesis is potentially better tolerability, potentially better selective weight loss, fat over lean muscle. So there's all those pieces. So I think the same rules are going to apply in terms of oral pills versus injectables. And what's great is this is really about giving patients different options. I think that's an important part of that.
It's my understanding that it's a relatively challenging technical endeavor to design an oral amylin. Maybe you could talk a little bit about why those technical challenges exist and how you were able to overcome them with the design of ACG2671. Yeah, so I'm smiling because I'm going
to sort of geek out a little bit sort of on this. You know, amylins are more complicated. It's got a protein called RAMP that binds to calcitonin receptors that then creates the amylin receptor. There are three different RAMPs, so there are three different amylins as well. There's this debate in the field about DACRAs versus SARAs as well. What's the right sort of molecule? It has a bigger binding site, a more complex binding site. So we're really proud. I mean, I'm incredibly proud of the discovery team. Many people, you know, I have many friends in the different pharmaceutical companies and they're like, you know, Ray, you know, they know that I've been focused on GPCRs for 30 years, but you can't make a small molecule to that. And the team did it. And not only did they do it, but we released back in January, our dosing for our SAD. You know, dosing scheme is 1, 2, 5, 10, 20 milligrams. It is a potent molecule. And so that's also really important as well. And then with this half-life, even more, with a big binding site with the complexity. So it was a tremendous, I think, scientific accomplishment to get there. Now that we're there, we know that there's a lot of competitors that are coming at us now that the patents have started to publish. And this is where I'm also really proud of our IP strategy, you know, it's worked in the GLP-1 space. We have more IP than anybody else on GLP-1 small molecules. Our amylin strategy is GLP-1 strategy on steroids. You know, we've really done a lot. We've made a lot of molecules. We have our discovery in Shanghai, China. It's where we started the company from the very beginning. So we take advantage of that chemistry, the chemistry resources there in discovery. So a lot of IP in order to maintain our first-in-class position
for that. You mentioned the DACRA versus SARA debate. I guess, what do you think is the important debate in terms of how amlens are going to perform in patients?
Yeah. So, you know, last ADA, Lily announced a molecule called the loralentide that showed some really, really good sort of properties. So it was really impressive. And that's where I think this heated debate got really sort of going over the past 12 months, whether, you know, really are SARAs, the ultimate, or DACRAs. This ADA, there was a symposia Friday afternoon one of the leading authorities in the field highlighted, he actually likes the Dacras because the calcitonin really shows opportunities in bone health. And particularly with sort of weight loss, when you're talking about lean muscle, one of the questions is, particularly in older population, is bone health a factor? And so the hypothesis is hitting the calcitonin pathway, you can really improve bone health. So the debate's continuing to go. It's not going to get resolved, I don't think, anytime soon. I think the amylin space really is the early inning still, early stages. We're going to see a lot of, you know, we continue to see a lot of molecules. We know the Dacrom mechanism is very safe. You know, cagrelinatide has been in thousands of patients or participants in the clinical trials, so we know it's safe. So it's going to be an exciting field. The debate isn't anywhere near resolved. From a structure perspective, we have 2671 that's now in phase one. It'll go into a phase 2A next quarter. So excited about that. That'll be a 12-week study. We also have another molecule going into the clinic in Q4 3535. That's a different chemical scaffold. We're making sure that we want to win in this amylin space. So we will put multiple molecules in the clinic. Not that there's anything wrong with our current molecule, but we're going to put multiple ones. And we'll put both Dacra and Serra's into the clinic from a small molecule perspective, while the peptide field continues to really educate us as to what's going on. I'm really grateful to the peptide field. They taught us so much. And we learn as we make small molecules, what's the best target product profile for a small
Are there other features that you think will be important other than DACRA, Sarah, as it relates to drug-like properties, et cetera, that you think will play a role in how amelins perform?
You know, I think that the same rules are going to apply that we applied to GLP-1. It needs to be a once-a-day drug. We don't think that there's really the sort of market for a twice-a-day drug. So that's part of our TPP. Safety is going to be, you know, up there. It's going to be, again, these are molecules, medicines that are being used by millions of people. Safety, the bars. I think combinability is really important. We think about early on. So we thought about from day one, we want this to be combinable with other medicines. And then, you know, the fourth one, and this is something, everybody uses this word access, accessibility, you know, during ADA for the last five days that we were sort of in New Orleans. And, but they're really not talking about accessibility in terms of price, you know, cost of goods. So we've spent a lot of time on manufacturing. We're really proud of our synthetic route of our manufacturing process. You know, the people that really need these medicines the most are the people that don't, they can't afford insurance. There's a, and we're talking about a global market as well. So it's really about numbers. This is really a volume play is how we look at it. And so we spend a lot of time and we're really proud of the manufacturing work that we've done to make sure these medicines truly are accessible. It's not just a word that people are using. They really are both affordable, no refrigeration, no requirements and costs that sort of comes from that. That's an important piece for us as well. Okay. What benchmarks
do you think investors should have in mind ahead of phase one data in both monotherapy and
combination settings? Yeah. So again, I want to manage expectations. In a phase one, we give one pill. You take one pill. Again, we're doing one, two, five, 10, 20 milligrams. So what we're looking for, first of all, safety. Is it safe? Was there any sort of issue with it? Second, PK. You know, we're looking for the, we have to have those PK numbers to design the 12-week multiple ascending dose study. So that's critical. Weight, you know, weight loss, people should not set any expectations. If I give you just one pill, don't, you know, let's not go there. But, you know, if I take lessons from the GLP-1 space when we did the SAD study, we went to the highest dose. We did see some of the, you know, gastrointestinal AEs. If you go straight to a high dose, yeah, you should see some of those. So, you know, that's another piece that, you know, we can start to see at the higher doses.
In terms of investing further behind the program, I guess, what should we anticipate with respect to additional studies, both on the monotherapy and, again, on the combination side over the
Yeah, so I think the combinations are going to be fascinating. We're really excited to get that started in Q4. The, you know, one of the scientific questions that we have is, is this, you know, is the combination mostly amylin with a little bit of GLP-1 or mostly GLP-1 with a little bit So we've got to work that out. That's a scientific question. That'll go into the combo design. You know, what's the perfect molecule? You know, the perfect molecule is very tolerable, you know, with good solid weight loss and having the right sort of range. So you mentioned, you know, Lilly did an attain-maintain study, and that was a good, they did a really good study. Lilly's done beautiful work. In that study, though, what they showed was ofroglipuron was okay relative to semaglutide. But relative to Zepatide, Zep bound, people regained weight. So, you know, olfoglipuron gives you 11% weight loss. That's the max. You know, can we achieve, you know, we're up to 16% right now. We still have more room. We haven't plateaued. So I think, you know, can we maintain more of that, you know, that mid-teens level of efficacy, the best-in-class profile that we have to date? Can that be maintained in a combo, in a switch, in a maintenance, long-term maintenance? So I think that's where, you know, we'll continue investigating.
What is your hypothesis with respect to the balance that you'll need to hit between GLP and AMLIN? Do you have any?
I do. The bet that I'm putting on the team, but we are debating this across the board. I think that it's more with this long half-life of AMLIN, what I'm excited about is, and how it would achieve steady state, it's probably going to be sort of more AMLIN with a little bit of GLP-1 kicker. but that's my bet. The team is pushing back, and the bottom line is we don't know. We just don't know. We need to do the experiment. There are no good models on tolerability.
How long are the studies that you'll have to run in terms of, like, number of weeks on drug or whatever to really kind of dial in the?
I think that the 12-week studies, the phase 2A studies, you have to still titrate relatively fast. It's still not a long. We want to spend six months on that maximum dose. that only gives us six weeks to get to the titration phase. And so part of the reason we're skipping the four-week study, we don't get anything meaningful out of the four-week study. Most of the weight loss is water. It gives a point where investors get some data, so they sort of like that, but it's not that informative. So we're going straight to the 12-week study. And then getting to the 36-week is really where we get the once-every-four-week titration. We sort of learn. We've seen a number of companies now that because they're trying to catch up, they're skipping some of these steps. I think that's dangerous. So, you know, we'll do the 12-week, the 36. That really educates us on how to then do the phase three. Because at the end of the day, you know, there'll be some volatility as we learn in phase two, volatility of, say, the stock. But the data that really matters at the end of the day, there's one piece of data that matters the most. The end of phase three, what goes on the label? That's what matters the most. And so we're optimizing for that.
Okay. Maybe last question for me in our final minute here is just you talked about having the cash on hand to run a phase three, but as you think about the broader development programs we just talked about, can you provide an update on cash runway and the specific activities that you have embedded within that guidance?
Yeah, absolutely. So, you know, the latest guidance is, you know, again, $1.5 billion cash as of the end of first quarter. It'll fund the Registrational Phase III study through the end of 2028. We'll deliver data on that. We also have our portfolio, including the AMLIN 2671, the 3535 programs that are in the clinic. 3535 will go into the clinic later this year. And with 2671, we'll be able to fund through the 12-week MAD study. and that will start in the third quarter, as Ray described.
Well, that brings us perfectly to time, so I appreciate all of the time and conversations this morning, guys. And thanks to everyone who joined us here and online.
Great. Thanks, Corinne. Thank you very much, Corinne.
Thank you. And good luck.