day and thank you for standing by. Welcome to the Structure Therapeutics top-line results from the Eleniglipron Phase 2 ACCESS Program. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you'll need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. In the interest of time, we ask that you limit yourself to one question today. Please be advised that today's conference is being recorded. I'd now like to hand the conference over to Danielle Keatley, Head of Investor Relations. Please go ahead.
Thank you and good morning. Earlier today, we issued a press release providing top-line results from Structure Therapeutics' ACCESS clinical program for Eleniglipron, our oral small molecule GLP-1 receptor agonist. A copy of this release and the presentation to accompany the call are available on the Investor Relations section of our website. Before we get started, I would like to remind everyone that some of the statements that we make on this call and information presented in the slide deck include forward-looking statements, which you see here. These forward-looking statements involve a number of risks and uncertainties that could cause actual results to differ materially. Please refer to the slide deck as well as our SEC filings for a more detailed description of the risk factors that may affect our results.
Please also note that these forward-looking statements reflect our opinions only as of the date of this call, and we undertake no obligation to update such statements to reflect events that occur after such date, except as required by law. Now, I will turn the call over to Raymond Stevens, our Chief Executive Officer, to start the presentation.
Thank you, Danielle. Good morning, everyone, and thank you all for attending the Structure Therapeutics' ACCESS program top-line data release. Today, we will present the results from our core Phase 2b ACCESS program and three additional ongoing clinical studies. For today's update, I will begin by discussing the Eleniglipron obesity market opportunity. Dr. Blai Coll, our Chief Medical Officer, will review the top-line 36-week data from our ACCESS, our core Phase 2b study. After reviewing the ACCESS study, Blai will share data from three ongoing clinical studies that provide additional information. Blai will then discuss Eleniglipron next steps, focusing on Phase 3 readiness. Finally, I will review Eleniglipron's role as the backbone in our oral small molecule portfolio before turning to Q&A. To begin, I want to reaffirm the mission that guides us at Structure Therapeutics: to make medicines accessible to all.
ACCESS to medicine is a fundamental human right, and everything we do is driven by that belief. The results that we're sharing today move us an important step closer to fulfilling that mission. As we think about how to make medicines more accessible to people living with obesity, I want to reground us in the obesity market. The currently available injectable peptides only serve approximately five million people in the United States. That's a very small fraction of the more than 100 million people in the United States who are living with obesity or overweight. Patients need more options. The world needs more options. Globally, by 2030, approximately 1.5 billion people are expected to be living with obesity or overweight and could benefit from medicines to manage their weight.
We know that patients need options and ACCESS , and only oral small molecules can scale to meet the needs of the global patient population. We believe that oral Eleniglipron, a medicine designed to be accessible, scalable, and combinable, represents an important solution in addressing this global challenge. Eleniglipron is a convenient once-a-day pill with no fasting requirements and one that can be stored and transported at room temperature. With a remarkably wide effective dose range, patients and prescribers will potentially have a great deal of flexibility on dosing with Eleniglipron, and because Eleniglipron can be easily combined with other oral medications, it will form the backbone for future oral combination therapies in development here at Structure Therapeutics.
Turning to the results on Slide 8 and the information you've all been waiting for, the data we are sharing today demonstrates that Eleniglipron has a compelling and differentiated profile and a best-in-class potential. Based on the data we're sharing today and our comprehensive and compelling Phase 2 program, we are ready to move into Phase 3 with an update on timing after our FDA meeting in early 2026. Starting with efficacy, for the ACCESS study, our core data set for Eleniglipron, at 36 weeks, patients on the 45, 90, and 120 milligram dose of Eleniglipron experienced 8.2, 9.8, and 11.3% placebo-adjusted weight loss, respectively. This data is clinically meaningful and statistically significant. In the exploratory ACCESS 2 study, patients experienced placebo-adjusted weight loss of 14.1% at the 120 milligram dose.
Notably, at the higher doses of 180 and 240 milligrams, patients experienced a remarkable placebo-adjusted weight loss of 14.4% and 15.3%, respectively. When looking across the four data sets that we're sharing today, we see no evidence of weight loss plateau beyond 36 weeks. In fact, we'll show evidence of continued weight loss beyond 36 weeks from the ACCESS open-label extension. Pharmacokinetics data from the study demonstrate that Eleniglipron is dose-proportional for doses up to 240 milligrams per day, which provides strong biochemical rationale for the differentiated efficacy data set for Eleniglipron. Beyond weight loss, we're pleased to report clinically meaningful improvements in blood pressure and blood glucose, hemoglobin A1c, in participants receiving Eleniglipron. Moving to tolerability, in the Phase 2b ACCESS study, we saw an overall 10.4% adverse event-related treatment discontinuation rate. The GI-related AEs were consistent with other GLP-1 receptor agonists.
In the exploratory Phase 2 ACCESS study, which we studied higher doses of Eleniglipron, participants who achieved re-randomization to higher doses at 28 weeks experienced no AE-related treatment discontinuations at the higher 180 and 240 milligram doses up to 36 weeks. In the ACCESS open-label extension and the body composition study, the data show a clinically meaningful improvement in tolerability dosing started at 2.5 milligrams. And importantly, this improved tolerability persists as we escalate to 5 milligrams compared to when we start dosing at the 5 milligram dose. Furthermore, when we stop the titration phase of the study at 2.5 milligrams per day, we see no discontinuations due to AEs. To date, up to approximately 10 weeks, a period when most others see most of the discontinuations due to AEs in the GLP-1 class of medicines. Now, turning to safety.
To date, more than 500 patients have been treated across all studies with Eleniglipron. Patients have had up to 44 weeks of exposure and up to 240 milligram dosing over 36 weeks. Among all of these patients, we have seen no events of drug-induced liver injury. I want to take a minute to pause and repeat this really important safety result. Among all these patients, we have seen no events of drug-induced liver injury. There have been no off-target safety signals across all dose levels and no events of QTc prolongation. I'll now turn the call over to Dr. Blai Coll, our Chief Medical Officer, to walk you through the details of the top-line data we are sharing today in the beautiful weight loss curves.
Thanks, Ray, and I'm very pleased to share the data of the Eleniglipron program today centered around ACCESS, the large Phase 2b assessing efficacy, safety, and tolerability of doses of Eleniglipron up to 120 mg for 36 weeks. In addition, we'll offer compelling and differentiating data insights into three of the most important questions for treating patients for chronic weight loss. Number one, are there any signs that weight loss is plateauing beyond the 36 weeks from our Phase 2b ACCESS study? We will provide data from the ACCESS open-label extension study to address these questions. Number two, can we dose higher than 120? And what additional efficacy, PK exposure, and tolerability do we observe? As you know, we specifically designed ACCESS 2 to explore doses up to 180 and 240 mg, and we're pleased to share the top-line at 36 weeks today.
Lastly, tolerability is associated with the starting dose. We wanted to explore if a lower 2.5 mg starting dose would further improve the tolerability of Eleniglipron. We explored this in two different studies, and we'll share data from the body composition study and the Phase 2 ACCESS open-label extension, both starting at 2.5 milligrams. We have generated a compelling set of clinical trial data from four studies, the top line of which will be presented today. The totality of this data provides clear and unambiguous evidence that supports the further development of Eleniglipron in a Phase 3 program for a chronic weight management indication. Let's dive into the data now with our core set for Eleniglipron, the randomized controlled Phase 2b ACCESS study.
230 participants with a body mass index equal or greater than 30 or 27 plus weight-related comorbidities were enrolled in 36 participating sites across the U.S. Participants were randomized to three different arms of Eleniglipron with doses of 45, 90, or 120 versus placebo. The starting dose was 5 milligrams with four week titration steps to achieve the target dose of each cohort. The primary endpoint was the percentage body weight reduction from baseline to week 36 based on the primary efficacy estimate, and we will also report today key secondary endpoints. It is important to note here that the ACCESS study used an eDiary, which was done to support the participants in the study. An eDiary prompts patients to report specific adverse events on a real-time basis as opposed to an unsolicited reporting of symptoms.
There is a well-recognized reporting bias associated with the use of eDiaries, and the team prioritized the use of the eDiary for patient support, knowing that this may have increased the risk of overreporting, as has been previously described. Because clinical sites were notified regularly of patients with symptomatology, the sites had the option to reach out to the participants and provide further guidance on diet, adjustment to the study drug, or symptomatic treatment based on their response. In Slide 12, we summarize the baseline characteristics of the participants, which are very consistent across study arms. Age range from 49 to 52 years, predominantly female, 53%-55%, with a baseline BMI of 39. HbA1c and blood pressure, according to the eligibility criteria, within normal limits. This population, in summary, adequately represents participants living with obesity or who are overweight with weight-related comorbidities.
So let's review the key efficacy findings in ACCESS. We are very pleased to report a clinically meaningful body weight reduction in those participants receiving Eleniglipron. As shown in the graph, there is a clean and swift separation of the curves starting at week 4 and continuing until week 36, with a clear dose response showing a 9% body weight reduction for the 45 milligram, 10.7% for the 90 milligram, and 12.1% for the 120 milligrams. Importantly, without any signs of weight loss plateauing. These findings translate into a significant reduction in absolute body weight ranging from 23 to 30 pounds, achieving a highly statistically significant difference compared to placebo at 8.2% reduction for 45, 9.8% for the 90 milligram cohort, and 11.3% for the 120 milligram cohort.
These results are consistent with the percentage of participants achieving different thresholds of weight reduction at the end of week 36, shown in the next slide. As you can see, more than 70% of the Eleniglipron-treated participants achieved at least 5% body weight reduction. In the 120 mg arm, 70% of participants lost at least 10% of their body weight, and nearly 40% lost at least 15% of their baseline body weight. It's also worth noting that these significant changes in body weight were associated with substantial reductions in both systolic and diastolic blood pressure and initial reductions in HbA1c in a population without hypertension or type 2 diabetes. Taken together, the results show Eleniglipron achieved a compelling level of efficacy in a dose range from 45 to 120 at 36 weeks. I would like to review now the tolerability in ACCESS.
In the next slide, we're showing the occurrence of nausea in the last panel, which peaked in the earlier part of the titration phase of the study. This temporal aspect of adverse events is an important concept that I would ask to keep in mind for a later section in our presentation today. The Y-axis shows the percentage of participants, and the horizontal axis represents time, with green, orange, and red indicating the severity of the events. Each one of the panels described the arms in the study, and as you can see, we observed the peak in nausea around 20% occurring in the first weeks when the three groups of Eleniglipron start at five milligrams. There is fluctuation over time, with the vast majority of events being mild to moderate.
Importantly, the number of events does not increase as participants are reaching the target dose, and nausea remains below 10% all the way to the end of the study. It's also important to understand the adverse events that led to treatment discontinuation, as indicated by the arrows in the slide. We observed an overall low AEs leading to treatment discontinuation of 10.4% in ACCESS. Importantly, a large majority, two-thirds of those discontinuations occurred within the first 12 weeks of the study, with a four-week starting dose of 5 milligrams, then going to 15 milligrams for four weeks before reaching 30 mg of Eleniglipron. On the right-hand side of the slide, we summarize the events of vomiting, where you can see a scattered occurrence of events with a prevalence also below 10% throughout the study for the three Eleniglipron arms.
Consistent with the findings on nausea, we do not observe an increase in vomiting as participants complete the titration steps and reach the target dose through 36 weeks. To summarize the tolerability of Eleniglipron in ACCESS, we see treatment-related discontinuations of 10.4% in the participants receiving Eleniglipron. It's important to note that the vast majority of participants in the treatment arms completed the study on treatment, ranging from 73%-78% compared to 75% in the placebo group. The study shows treatment discontinuations due to adverse events ranging from 7.7%-13.3% without a clear dose response, similarly to what was observed for the most commonly reported adverse events listed in the table. The lack of dose response may be due to the events accumulating in the beginning of the titration phase, where the three arms share the same dosing.
As mentioned in the design slide, the use of the eDiary should be taken into account in the interpretation of those results. To summarize our core Phase 2b ACCESS study, Eleniglipron shows compelling efficacy from 45 to 120 mg, with body weight reduction ranging from 8.2%-11.3%, respectively, without signs of plateauing up to week 36. We have observed the expected gastrointestinal-related events, as known by the class of GLP-1 receptor agonists, with a manageable profile that achieved an overall 10.4% treatment discontinuation. Let's move now to the first question of the three exploratory initiatives we want to share data with you today. As you know, there is intense interest by doctors, payers, and patients in when a particular drug reaches a plateau in efficacy.
So we use the data from the ACCESS open-label extension to ask the question, is there a weight loss plateau for Eleniglipron beyond 36 weeks? In Slide 19, we describe the design of the ACCESS OLE, where participants in the 45 milligram arm in the double-blind portion of the ACCESS study were titrated to 60 milligrams for four weeks and then 90 milligrams. The 90 and 120 milligram arms of ACCESS continue in the OLE at 120 mg, and those on placebo started at 2.5 mg of Eleniglipron during four weeks and were up- titrated to 5 mg. The ACCESS OLE study is still ongoing and will provide additional longer-term safety and efficacy data while providing ACCESS to drug for patients.
Today, we report interim data from 143 participants that represent the majority of the eligible participants at week 36, up to eight weeks after the rollover from the ACCESS study. In the next slide, we show the summary of the efficacy observed where the participants who were on placebo in the ACCESS study started their dosing in the OLE at 2.5 milligrams and were titrated to 5 milligrams. They experienced a clinically meaningful 3% body weight reduction at the end of the first eight weeks. Additionally, and to answer the question of a plateau, participants in all those cohorts previously treated with Eleniglipron continue to experience additional body weight reduction ranging from 1.1 to 1.3%, indicating no weight loss plateau after 36 weeks. Let's now move to the second exploratory question. Can we dose higher than 120 milligrams, and what would be the impact on efficacy, exposure, and tolerability?
For that, we designed our ACCESS 2 study, and we're very excited to share this data with you now. The exploratory Phase 2 ACCESS 2 study originally enrolled 85 participants in two sites across the U.S. 12 of these participants were part of a Sentinel group, which aimed to provide preliminary data to the Independent Data Monitoring Committee regarding the 180 milligrams a day dose before moving to higher doses in the main study group noted in the second row of the study schema. This main study group included 73 participants, 61 allocated to Eleniglipron, and 12 to placebo. In ACCESS 2, the starting dose and titration steps were the same as in ACCESS, starting at 5 milligrams. At week 28, the remaining participants at 120 mg of Eleniglipron were re-randomized to three groups.
One group stayed on 120, the second titrated to 180 milligrams, and the third group titrated to 180 milligrams for four weeks and ultimately reached 240 mg. We report data from the pre-specified analysis at 36 weeks today. The study is still ongoing and will complete at 44 weeks. Slide 23 summarizes the baseline characteristics, which are comparable to ACCESS, with an average age around 50 years old, predominantly female participation, with a baseline BMI ranging from 36 to 39.9. In the next slide, we're excited to present that very meaningful greater efficacy was achieved with higher doses of Eleniglipron above 120. Consistent with the results of our core Phase 2b ACCESS study, here we see a clear separation, of course, from placebo from the beginning of the study with body weight reductions continuing to week 36 and with no signs of weight loss plateauing.
It's interesting and very reassuring to point out that with both ACCESS and ACCESS 2 studies at 120 milligrams of Eleniglipron, we see consistency in the body weight reduction at week 28 at around 10%. Let's now zoom into the box at the lower right-hand side of the graph to see what happened after the re-randomization when patients were up- titrated to 180 or 240 mg. Where you can see in the left panel, the participants continuing on 120 after the re-randomization phase achieved a 13.1% body weight reduction from baseline, and the two groups exposed to 180 showed directional separation at week 32. Importantly, those participants that titrated up to 240 experienced an even greater body weight reduction reaching 14.2%.
Translating these to placebo-adjusted numbers, the 120 dose achieved a 14.1% body weight reduction, 14.4% for the 180, and 15.3% for the top dose at 240, which corresponds to 35.5 pounds of weight loss at week 36, highly statistically significant and clinically very relevant. Importantly, we observed proportional dose exposure with Eleniglipron up to 240 milligram dose, reinforcing the dose response in body weight reduction between 120 and 200 milligram groups, and indicating the remarkably wide effective dose range of Eleniglipron observed to date. Let's transition now to the tolerability profile of Eleniglipron in participants receiving higher doses. In Slide 26, in the left panel, we show the occurrence of nausea during the first 28 weeks in the study before re-randomization with a target dose of 120 mg.
In the panel on the right, we show the occurrence of nausea after re-randomization from 120 to 180 to 240 and placebo. We observed fluctuations in nausea in the first phase of the study with a slight increase in events while participants titrate to 120 mg, and the events attenuate over time. As seen in the panel on the right, only two participants who titrated from 120 to 180 milligrams showed intermittent events between weeks 33 and 36. Very importantly, all of the discontinuations due to adverse events happened during the titration phase from 5 milligrams to 120, as indicated with the arrows, with approximately half of the discontinuations occurring in the first 12 weeks of initiation, as consistent with the ACCESS study. No discontinuations due to adverse events occurred in participants who were up- titrated from 120 to either 180 or 240.
In the next slide, we're summarizing the events of vomiting that followed a similar temporal pattern with a far lower number of participants reporting events, less than 15% throughout the study. With one participant in the higher dose phase at 120, no patient in the 180 milligram group, top right quadrant, and only one participant in the 240 milligram group in the lower left quadrant reported intermittent vomiting events between weeks 33 and 36. To summarize the tolerability in ACCESS 2, we observed 17 participants discontinued due to adverse events during the titration phase from 5 to 120 milligrams, at 27%. 11, 18% discontinued due to other reasons, non-adverse event related. Six participants remain on Eleniglipron at a dose lower than 120. It is worth noting here the number of discontinuations being higher than in ACCESS. As we have described, these are different studies.
The presence of the OLE in ACCESS is an example, with also different clinical sites where variability can be expected. But importantly, we see a similar trend of accumulation of both gastrointestinal events and discontinuations in the first titration steps of the study. The most critical question in ACCESS 2, though, was the tolerability once participants reached higher than 120 mg doses, and the study did not observe discontinuations during the 180- and 240-mg dose phase, which is very promising data. Similarly, the most commonly reported gastrointestinal events declined in frequency as participants moved to the higher dose phase.
In summary, we are very pleased with the results of ACCESS 2, answering the additional activity of Eleniglipron at higher doses than 120 mg, with directionality in efficacy up to 240 mg, with 1.2% additional body weight reduction after four weeks compared to 120 mg, associated with proportionality in exposure, and very importantly, with a tolerability profile once participants reached 180 mg and 240 mg, showing no discontinuations of treatment due to adverse events. And that brings us to the last question. In next slide, will a lower 2.5 milligram starting dose further improve tolerability of Eleniglipron? As you have seen from our core Phase 2b ACCESS study, there is a pattern of peak incidence for both nausea and vomiting observed in the beginning of the 5 milligram dose.
In both the studies, ACCESS and ACCESS 2, the majority of treatment discontinuations occur in the first three titration steps up to 30 milligrams. With that in mind, we pose the question, if we started lower and went slower, dosing at 2.5 instead of 5, would we observe a further improved tolerability profile? We collected data from two studies in which we started dosing at 2.5, our Phase 2 body composition study and our ACCESS open-label extension study. Next slide, we describe the designs of the open-label extension on the left, where the participants on placebo during the double-blind treatment phase transitioned to 2.5 milligrams of Eleniglipron for four weeks before escalating to 5 milligrams. The body composition study on the right enrolled 71 participants with similar eligibility criteria to the previous studies done in 11 sites in the U.S.
In this study, 59 participants have been randomized to Eleniglipron at a starting dose of 2.5 milligrams compared to 5 starting dose in ACCESS and ACCESS 2, and 12 participants to placebo. We will report today the results from a pre-specified analysis after a median follow-up of approximately 10 weeks. Baseline characteristics are consistent with previous studies. Participants in the mid-50s, predominantly female, with a body mass index between 38 and 39. In the next slide, we describe the occurrence of nausea. We report comparable results of nausea between the 2.5 milligram starting dose and the placebo group and below 10%, and also sporadic events of vomiting at the 5 milligram up titration, with no discontinuations of treatment due to adverse events after a median follow-up of approximately 10 weeks.
To summarize the tolerability, in this slide, you can see a vastly lower incidence of nausea and vomiting when we started the 2.5 mg dose of Eleniglipron. Remarkably, and unlike our experience in ACCESS or ACCESS 2, we observed no treatment discontinuations in the first 10 weeks of dosing. We find this result very encouraging. To summarize the tolerability of the lower 2.5 starting dose versus the 5 mg starting dose, we want to take the opportunity to put all the pieces together in this slide and walk you through the cross-trial comparison on the impact of different starting titration doses on the tolerability of Eleniglipron. We plot in the graph the occurrence of nausea in the blue bars and vomiting in orange bars across the studies displayed in the horizontal axis.
Starting from the far left with ACCESS, 22% of participants reported nausea in the first four weeks when starting at 5 mg, and 6.9% experienced at least one event of vomiting. Those results were consistent with ACCESS 2, also starting at the same 5 milligram dose and reporting 21.1% and 11.3% of nausea and vomiting, respectively. Conversely, when we analyze the results from the ACCESS open-label extension participant showing the middle panel, we see minimal nausea, 5.7%, and no vomiting in participants starting at 2.5 mg, and no events in weeks 5 to 8 when they were up-titrated to 5 milligrams. In the panel on the right, we show the results from our body composition study in which we took the opportunity to start all participants at 2.5 mg.
We report 15% of nausea and 1.7% of vomiting in the first four weeks, decreasing to 6.5% and 4.3% of nausea and vomiting, respectively, when participants up- titrated to 5 mg. Most important, and unlike in ACCESS and ACCESS 2, there were no treatment discontinuations in the first eight weeks of dosing, and recall that the 2.5 milligram dose is meaningfully active in terms of weight loss, as we've shown in the ACCESS open-label extension study. Based on the observations that the 2.5 starting dose is active and starting titration with the 2.5 results in further improvement of the tolerability profile, we plan to initiate the Phase 3 program on all future studies at the 2.5 milligram starting dose, following the approach of start low and go slow. Lastly, we want to turn to the next slide to highlight an important aspect of the program that is the off-target safety data.
In Slide 36, we describe the events of liver enzymes fluctuations seen in the four Phase 2 studies described today. As Ray mentioned, we have no cases of drug-induced liver injury, no increases of 10 times the upper limit normal, and infrequent fluctuations in ALT, AST, three and five times upper limit normal distributed across different arms, including the placebo, without a clear dose response. It is important to remark that those participants experiencing elevations in liver enzymes continued study drug, and ALT, AST return to the baseline values. For a drug that is potentially going to be taken by millions of patients chronically, we interpret these results as highly encouraging, indicating a safe liver profile with Eleniglipron. To wrap up, we covered a lot of ground this morning, so I want to spend some time summarizing all the findings from our Phase 2 program.
In regards to efficacy, we demonstrated statistically significant and clinically highly relevant body weight reductions achieved with three doses in ACCESS up to 11.3% placebo-adjusted for the 120 milligram arm. Exploring higher doses up to 240 milligrams yielded directional, meaningful additional body weight reduction up to 15.3% placebo-adjusted for the 240 milligram arm. Importantly, there are no signs of the activity leveling off up to 44 weeks, and we have observed clinically meaningful improvement in both blood pressure and HbA1c. We observed proportional exposure with Eleniglipron, indicating a high degree of dose optionality from 45 to 240 of Eleniglipron moving forward. For the tolerability, Eleniglipron showed the expected gastrointestinal-related events consistent with the mechanism of action of the GLP-1 receptor agonist. We observed an overall 10.4% treatment discontinuations due to adverse events in our core Phase 2b ACCESS study.
Despite a higher discontinuation rate in ACCESS 2, when exploring higher doses of Eleniglipron, we see only slight increases in nausea and vomiting, but importantly, those events were manageable and did not trigger treatment discontinuations in the 180 or 240 milligram dose cohorts of the study. Lastly, we observed clinically meaningful improvements in all tolerability parameters when we started dosing at 2.5 of Eleniglipron, and unlike in ACCESS and ACCESS 2, there have been zero AEs-related discontinuations observed today, which critically informs the design and titration regimen for the Phase 3 clinical development. To complete the summary, with more than 500 participants dosed with Eleniglipron up to 44 weeks of exposure and top dose of 240, we are very pleased to report no events of drug-induced liver injury, no off-target safety signals, and no events of QTc prolongation.
To conclude, we would like to summarize the results that position Eleniglipron Phase 3 ready. We assessed the efficacy, safety, and tolerability of Eleniglipron in the ACCESS study, and based on the data to date, we answered the three additional questions. No weight loss plateau, dose response activity confirmed up to 240, and clear tolerability improvements starting at 2.5. Those three pillars robustly inform the Eleniglipron Phase 3 program to pursue a chronic weight management indication, and as indicated in the bottom of the slide, we've already completed the API manufacturing, and the drug product manufacturing is well underway for an anticipated mid-2026 FPI. With that, let me turn it over back to Ray.
Thank you, Blai, for the exciting and very strong results shared today.
From the data that you've seen presented, Eleniglipron is differentiated and has the potential to be best-in-class oral GLP-1 small molecule. The totality of the data presented today provides substantial evidence that Eleniglipron is a compelling medicine with best-in-class potential for activity, best-in-class off-target safety, and favorable tolerability with the 2.5 milligram starting titration dose. As such, we believe Eleniglipron is well positioned to capture a significant portion of the growing chronic weight management market. In particular, I'd like to highlight that according to our market research, the biggest growth opportunity for oral medicines for obesity is with the primary care physicians or non-specialists. What they're looking for are options that are effective, convenient, flexible in dosing, and accessible to their patients. Oral small molecule pills manufactured at a global scale represent a new option to meet these unmet needs for the growing number of non-specialist prescribers.
However, Eleniglipron is only one piece of the portfolio we are building here at Structure Therapeutics. We have the goal to build a broad oral small molecule metabolic portfolio. In addition to Eleniglipron, I'm excited to highlight the current status of our amylin program. We now have two amylin-targeted molecules, ACCG2671 and ACCG3535, that are in development. ACCG2671, we're pleased to announce that the IND has been cleared by the FDA, and Phase 1 initiation is well underway. We believe that ACCG2671 is the industry's most advanced oral small molecule amylin receptor agonist. For our second-generation DACRA, the development candidate ACCG3535 was selected last month. We view Eleniglipron and our amylin molecules as foundational backbone molecules that can be combined with our portfolio of other oral small molecules.
In addition, we have programs underway to combine these two backbone molecules with our GIP and glucagon receptor oral small molecules in discovery. Beyond obesity, we're evaluating potential indication expansions for these molecules in chronic kidney disease, MASH, hypertension, heart failure, sleep apnea, type 2 diabetes, osteoarthritis, and addiction. 2025 was a very successful and productive year for Structure Therapeutics. We have a strong and broad portfolio of obesity-related oral assets. As you've heard today, we now have five different studies for Eleniglipron. As mentioned, we anticipate being ready to move into Phase 3 development by mid-2026. Our lead amylin program is moving into the clinic, and we're also very excited about our combination opportunities with our GLP-1 and amylin combination pill entering IND enabling studies and continuing progress in our discovery research on GIP and glucagon.
As we wrap up our prepared comments, I'll highlight our upcoming catalyst for 2026, building on the accomplishments from 2025. In the first six months of 2026, we'll have our end of Phase 2 meeting with the FDA. You will see our top-line results for our ACCESS open-label extension study, ACCESS 2 extension study, and our body composition study. In the summer of 2026, we plan to be ready to initiate the pivotal Phase 3 studies. In the second half of 2026 for Eleniglipron, you'll see top-line results from our switch study investigating the safety and efficacy of switching patients from an injectable selective GLP-1 receptor agonist to our oral Eleniglipron for weight maintenance.
We also expect to share top-line results for our studies in patients with type 2 diabetes plus obesity at higher doses than we previously studied in type 2 diabetes to support Phase 3 and label inclusion. Turning to our amylin franchise, in the second half of 2026, you'll see our initial oral amylin ACCG2671 Phase 1 study results and the initiation of our second oral amylin ACCG3535 into the clinic. As a closing remark, I want to thank all Structure Therapeutics employees for the years of hard work and dedication in developing Eleniglipron, as well as our clinical investigators for their partnership. Most importantly, we extend our deepest gratitude to the more than 500 participants who have enrolled in our Eleniglipron clinical program to date. Their trust and commitment are essential to advancing this medicine and to fulfilling our mission of making medicines more accessible to all.
Eleniglipron has tremendous potential to change lives, and we look forward to advancing Eleniglipron into Phase 3 and beyond. I will now open the call for Q&A.
As a reminder, for your last question at this time, please press star 11 on your touch-tone phone and wait for your name to be announced. To withdraw your question, please press star 11 again. In the interest of time, we do ask that you limit yourself to one question today. Our first question will come from Evan Seigerman with BMO Capital Markets.
Hi guys, thank you so much for taking my question. I would really love it if you could talk through how you think about the PK properties of Eleniglipron and how that might have contributed to both the efficacy and tolerability that we saw today.
Specifically, what do you think is driving the higher efficacy that we're seeing here versus some of the other competitors in the oral small molecule space? And maybe any nuances with the product's half-life that could contribute to higher GI symptoms, you know, trying to optimize that aspect as you think about Phase 3. Thank you so much.
Thank you, Evan. This is Blai. I'll take the call. So we're very pleased with the PK profile, as we've shown in the slides and in the presentation. We are seeing proportional exposure when compared to 120 milligrams versus 180 and 240. And that's a clear differentiation element from Eleniglipron. And that's also consistent with the directionality in the additional body weight reduction that we've seen with just four weeks of exposure to 240. So those two pieces of data are very closely related.
We see higher and proportional exposure between 120 and 240, and with a limited period of time of doses up to 240, we see the directionality in additional body weight reduction, so we're very, very pleased about the result of ACCESS 2 on that end. You're mentioning the PK characteristics and the half-life. I think this data set once again demonstrates that we have a once-a-day orally available small molecule, highly efficacious and a very competitive profile.
Thanks for the question, Evan.
Our next question comes from Seamus Fernandez with Guggenheim.
Great, thanks so much, and congrats on the data. You know, it looks like the 2.5 milligram dose has really helped to resolve some of the early tolerability issues that you see emerging. I wanted to just get your sense of how you would hope to advance into your Phase 3 clinical program. Is it obvious?
It seems obvious to us that the 2.5 milligram dose is, you know, resolvable there and should be utilized. I guess the other question is, as you sort of plan for Phase 3, how do you think about the dose range that should be explored as you kind of pursue the additional data? Do you need the 44 weeks to really decide on the top dose from your perspective, or do you feel good that, you know, a 90, 120, 180 feels like the right profile? It looks like they're pretty tight in terms of their, you know, sort of dose-response relationship. And then just the final question, you know, it's only 10 weeks' worth of data with the 2.5 milligram dose, but can you just provide maybe a simple order of magnitude reduction that you're seeing in the frequency of vomiting and nausea? Thanks so much.
Thanks, Seamus. So we'll go one by one. We completely agree with the 2.5. I think the data is very, very clear by starting at 2.5 and remaining at 2.5 for four weeks. It abates the majority of the adverse events that we saw by starting at 5 milligrams. I think the data set is very, very clear and points in that direction for starting the newest studies, including the Phase 3. In terms of the top dose, whether we go to 180 or 240 for Phase 3, I think the important bottom-line data here is that we have full characterization of efficacy and tolerability for starting at 2.5 all the way to 240 milligrams. That gives us the flexibility and the optionality to design what's the best dose for the Phase 3. We'll have that option.
We just got the top-line results, so we need to go through the full data and also continuing with the modeling work to define the doses for Phase 3, but it's really, really positive and encouraging to see that full characterization from the 45 milligrams in the low end all the way to 240, and then the third piece of your question, you're mentioning the 10 weeks and how that translates into improvements in tolerability. We did not see any event of discontinuation up to 10 weeks in the body composition, and there's no event of discontinuation of a study drug in the open-label extension either, so those two are very clear indicators.
And then when you compare the five milligrams with the five milligrams, so when you compare the five milligrams at the body composition or the OLE compared to the five milligrams ACCESS 2, we see more than half reduction in both nausea and vomiting, which is also very, very encouraging preliminary results. So in summary, we're very pleased with the starting dose at 2.5, and we're also very pleased to have full characterization all the way to 240.
Our next question comes from Terence Flynn with Morgan Stanley.
Hi, thanks for taking the questions. I guess the first one I had is, you know, there were some reports that the FDA could move to single Phase 3 trial for approval. So just wondering, you know, your perspective on that, Ray, as you think about the scope of the Phase 3 program. Obviously, you have some time here.
And then the other question is just, can you remind us about the switch study that you are conducting and what you're hoping to show in that? It sounds like you're using, you know, GLP, injectable GLP, not GLP-GIP, but just wanted to confirm some of the metrics there and what the goal of that study is. Thank you.
Thank you, Terence, for the question. I'm going to hand this question over to Blai.
Yeah, thank you. The single Phase 3 trial, this is an intriguing concept. Of course, you know, usually the guidance that the FDA issued back in January, we're still talking about the 3,500 participants exposed to dose at least for 52 weeks and 1,500 on placebo. That's the most recent update from the FDA.
Now, whether these can be executed as one single clinical trial or two, that, you know, will depend as well on the future discussions that we're planning to have with the agency in the first quarter of next year. In terms of the switch, we're very excited about the switch study. It's an ongoing study. And what we want to interrogate that study is exactly on two questions. One is, what is the right dose to transition from an injectable into Eleniglipron? Because that has never been explored before, and we need to generate that data. But then second, also very, very important is how well are we maintaining our body weight reduction up to 12 weeks after the transition? So these are the two questions. The study, as I said, is ongoing, and we're very excited about the prospects of that strategy.
Terence, I would also add, I view it as a very positive sign. The action that's being taken by the current administration in regards to recognizing the importance of GLP-1s and Structure Therapeutics is very well positioned, giving our oral small molecule cost of goods, our manufacturing capabilities, and even the signaling that we're getting from the FDA with their recent guideline update with further clarity. So I think all of this bodes very well for developing Eleniglipron into the market.
Our next question comes from Yasmeen Rahimi with Piper Sandler.
Good morning, team. Congrats to the data and really thorough presentation. I guess, team, as we think about starting with 2.5 and then going to 120 and potentially even 240, what do you think could we achieve the same weight loss magnitude that you guys just shared with us across ACCESS 1 and ACCESS 2?
Just wanting to understand, could we end up at the same weight loss magnitude by just stretching and going slow over a longer durability? And this is specific to, you know, the OLE study that's ongoing. So if you could share your thoughts around what we hope to see at week 28 when we get to the 90 dose group, that would be helpful. And then the second one is a clarification. Do you need to see the 2.5 milligram OLE data before you finalize your Phase 3 development and how you're thinking about titration schedule?
Thank you, yes. So it's Blai. I'll take that again. So starting at 2.5 and going to 120 or 240, I think there's a piece of information there that it's very, very critical that we see preliminary signs of efficacy by starting already at 2.5.
And I think this is very, very important because, of course, that can help control the discontinuations of some of the placebo participants in the beginning of the study. But most importantly, it provides the opportunity to have a healthy body weight reduction, especially in the beginning and during the titration phase. And so that's really, really relevant, and we're very pleased with the data that we have so far coming from the 2.5. In regards to your second point, the need of CVOT before starting the Phase 3, that's not a necessary step. So we're good to go to start with the identification of the doses that we want to move forward into Phase 3. And as I indicated, I have a meaningful interaction with the agency in the first half of next year to position the program Phase 3 ready.
Yes, one of the things that we did a number of years ago was when we were doing our research with physicians about what did they want to see in terms of GLP-1 medicines. Every single time the first word out of their mouth was dose flexibility. That because of the demand, they wanted to have as much flexibility as possible with their patients. And we think Eleniglipron is really well positioned with its very broad dynamic range from 2.5 milligrams all the way up to whether they go to 90, 120, or 240, gives physicians a really good opportunity with dose flexibility.
Our next question comes from Samantha Semenkow with Citi.
Hi, good morning. Thanks very much for taking the question, and congratulations on the data this morning. Just a bit of a clarification for the body composition study.
Can you just share a bit about that patient population, how it compares to the patients enrolled in ACCESS and ACCESS 2? I'm wondering just, you know, how similar is it that we can really extrapolate the tolerability data that you shared to a potential Phase 3 study population? And then just a second question. When we think about a potential partnership or acquisition for Eleniglipron, can you talk about how we should think about the oral amylin assets potentially fitting into this conversation? Thanks very much.
Blai, you take the first part.
Yes, I'll take the first part. So the baseline characteristics are comparable, Sam. The eligibility criteria was also very, very similar between the studies, and all of them have been done here in the U.S.
Average age is around 54, 48 in the body comp, predominantly female, 64% to 66% female participation, and baseline body mass index between 38 and 39. Pretty comparable, and then normality in terms of HbA1c and the rest of the baseline characteristics.
Sam, in regards to your second part of your question in terms of strategics and, you know, the way that we view this, we've been building a very strong and broad portfolio of our Eleniglipron, our amylin franchise, as well as the other molecules. It's really, you know, we have, I think, a very strong portfolio. With this data now in hand, we'll continue having that dialogue with strategics.
Our next question comes from Dave Risinger with Leerink Partners.
Thanks. Thanks very much. Let me add my congrats as well to you, Ray, and the team.
So just to follow up on that last question, could you provide a little bit more color on, you know, the potential for partnering discussions, including the potential timeline? Obviously, there's a lot of data to go through, but any additional color would be helpful. And then since others are asking an additional question, I'll ask one more, which is, Bly, could you talk a little bit more about the use of patient eDiaries and contrast that with how competitors have conducted their trials? Thanks so much.
Blai, you want to take the second part, and then I'll take the first part.
Sure. Thanks, Dave. So yeah, the use of eDiaries is not very commonly instituted in this field. We wanted to do that because we wanted to prioritize the patient journey and making sure that we have the adequate support for those participants.
The difference there is that we're proactively asking the participants about their symptomatology on a real-time basis, and that, of course, has the potential to overinflate the incidence of those events that you've seen in the table. There are other studies that have done that, and so if we compare, for instance, the reporting of nausea in the placebo arm when you don't use an eDiary, it's around 10%. Contrasting that to those studies that use an eDiary, we're seeing around 20% of placebo event rates for that symptom specifically, and I'm just using that as an example, and we can use that as a proxy to indicate that, you know, we're seeing doubling the events by proactively asking instead of just not reporting unsolicited, so that's the decision that we made, again, because we wanted to have full support to the participants in the study.
And Dave, in regards to your first question, these data are clearly very, very strong. We have a very safe drug in terms of off-target safety, best-in-class efficacy, a clear path for Phase 3 dosing for tolerability, clear path for Phase 3 and to market, excellent manufacturing. I mean, one point that we didn't stress on this call because there was so much data, but our ability to manufacture this, you know, we can manufacture 6,000 metric tons, enough for 100 million patients per year. We really have a solution at a very large scale. So with all of this in hand, you know, we're looking forward to continuing discussions with strategics now that we have this data. We know everybody's been waiting.
Our next question comes from Roger Song with Jefferies.
Great. Ray, congratulations. Maybe at this point, a little bit of kind of final question.
First is, I think you mentioned most of the AE is in the first couple of cycles. Can you just give us a little bit of number on the percentage AE in the first eight weeks and 12 weeks? Because you give us the 2.5 starting dose, and then, you know, just try to estimate how much lower the AE for the 2.5 milligram starting dose. And then also in your ACCESS 2, that discontinuation due to AE go up quite a bit compared to ACCESS. Maybe that's due to the small N, maybe the open-label extension. Maybe just give us a little bit of context there. How should we think about this 27.9% versus 11%? Thank you.
Thanks, Roger. I'll take the first one. So the data on the 12-week in the body composition or the OLE, those two studies are still ongoing.
We have a median duration up to 10 weeks. But of course, that enrollment has been scattered, and so we're continually collecting the data. I think it's really encouraging, though, to see the differences between the first four weeks and the second four weeks while titrating to 5 milligrams. And as we've indicated, the fact that we don't have any discontinuations and that there's approximately half drop in the adverse events, I think it's really, really encouraging. Differences between ACCESS 2 and ACCESS, yeah, there are differences. These are two different studies. We use different clinical sites. We use an open-label extension in ACCESS. We didn't do that in the exploratory ACCESS 2, that it goes to 44 weeks. And those things may play a role explaining that variability that we're seeing in between both the studies.
The most important thing, though, when looking at the adverse events is that both the studies share a commonality that is an aggregation of both the tolerability events and the AEs leading to discontinuation in the beginning of the studies, starting at 5, going to 15, and going to 30, and so that's the powerful insight there. Because then if you couple that with the data that we have starting at 2.5, the next step is very, very clear to start at 2.5 so we can mitigate that initial tolerability and the initial discontinuations. Thanks for the question. This is a very relevant topic.
Our next question comes from Prakhar Agrawal with Cantor.
Hi, good morning, and thank you for taking my questions, and congratulations on this comprehensive update.
So maybe just add to, firstly, on the Manhattan plots, on the time course of the nausea and vomiting that you provided, if you can just put it into context versus what orforglipron showed on the prevalence chart and how persistent were these nausea and vomiting events, especially towards the better part of the trial. And just a quick clarification, the efficacy results are efficacy estimate. I know you will be presenting the ITT details sometime later on, but if you can qualitatively comment on how close the ITT data we're tracking relative to the efficacy estimate and these readouts. Thank you.
And Blai, we're going to need to keep this answer short. And I'm going to remind everybody, we really need to have one short question because the markets are open, and we're over time.
Thanks, Prakhar.
Talking about the Manhattan plots versus other compounds, the most important thing here is the trend that we're seeing, that we peak in the first four weeks. And that's, again, starting at five milligrams. And that's, again, coming back to the start of 2.5, that we're seeing a dramatic difference and a dramatic improvement. Compared to others, it's always very challenging to have cross-trial comparisons, as you well know. We don't have the same display from that molecule that you mentioned in the Phase 2b, where they composite the four events. But most importantly, I think what we're seeing here in terms of a peak in the beginning at five milligrams and then attenuating over time, that's very consistent. In terms of efficacy, we've reported the primary efficacy estimate as indicated in the slides.
We do not anticipate a lot of changes with the treatment estimate because the majority of the participants are still on treatment and in the study. But what we reported today, just to clarify, is the primary efficacy estimate.
Our next question comes from Hardik Parikh with JP Morgan. Hardik, your phone may be on mute.
I'm sorry. Thank you for taking the question. Just one high-level one from me. From a competitive positioning perspective, how do you look at this data when you take into context both orforglipron ahead of you and then also some other oral small molecules in clinical development alongside you? Thank you.
Thank you for the question. We're very pleased. We think we're in a great position. We believe that we are potentially best in class. The efficacy is very, very strong. The safety profile is very, very strong.
We have a solution on the tolerability with a 2.5 milligram start. And so with all this in hand, we think that we're in a really good position to take a significant market share in the GLP-1 space.
Our next question comes from John Wolleben with Citizens.
Hey, thanks for taking the question. Based on what we know from other programs, the PK you're seeing in your modeling, when do you expect weight loss to plateau with Eleniglipron?
John, good question. This is Blai. So the most important thing is that we have not seen plateauing all the way to week 44. And this is something that it's truly differential here. And the curves are remaining as of some of the injectable data. And as you know, when you looked at the Phase 3 of those programs, the weight loss plateau usually is seen in the 60-62 weeks.
And so up to 44 weeks, we're seeing a similar pattern. So the prospects are to emulate here what we've seen in injectables in the past. And the initial indications are pointing in that direction.
Our last question comes from Patrick Dolezal with LifeSci Capital.
Hi, thanks for taking the question. Are there any learnings on the magnitude of HbA1c changes as it relates to the potential of Eleniglipron in type 2 diabetes? I know we're just digesting the top-line obesity data here, but would love to sort of hear how your thoughts are progressing as it relates to the potential of Eleniglipron and follow-on indications. Thanks.
Thank you, Patrick. Yeah, we also mentioned in the slide, we see meaningful reductions in HbA1c. We're talking about a 0.3% reduction at the end of week 36.
And taking into account that that reduction happens in participants in the study that are not participants diagnosed with type 2 diabetes, which I think it's highly, highly relevant, also aligned with a significant reduction in systolic and diastolic blood pressure, along with the clinically relevant body weight reduction. And so I think this data is also very, very encouraging to explore indications in the future for type 2 diabetes participants. And as we announced as well, the study with type 2 diabetes and high BMI is also ongoing.
We have a question from a line of Corinne Jenkins with Goldman Sachs.
Thanks. Good morning. How many titration schemes do you think, based on these data, you'd like to take forward into Phase 3?
I'm curious how you're thinking about the study duration that will be needed to fully elucidate that efficacy profile, given sort of the number of steps that might be required to get up to the final dose. Thanks.
Thanks, Corinne. Yeah, I'll take that. So I think it's very clear that the optimal starting dose is at 2.5. Also very clear that the four-week titration is the way to go. Now, the questions that you're asking, rightfully so, it very much depends on how much we want to go high in dose and what will be the top dose that we will declare for the Phase 3. We think it's important in a chronic therapy to take the time to titrate, make sure that the tolerability is optimized while we continue augmenting in the body weight reduction. Good questions.
But again, as I said, it depends on how high do we want to go in terms of the top dose in the Phase 3.
This question comes from Annabel Samimy with Stifel.
Hi, thanks for taking my question. I guess I'm curious, if you observed any kind of durability issues for the patients who did not move into the OLE study, what kind of weight loss persistence did you see there, and what were the reasons for not moving into the open-label study for these patients? Thanks.
Yeah, thanks for the question. So the efficacy that we've seen after starting the OLE, we've described that, and we're very pleased to see the initial body weight reduction in the placebos that transition over to drug, and then in the three doses.
In regards to the rolling over into the OLE, the vast majority of the participants completing week 36 transition over to the open label extension, which speaks very, very highly about the interest in continuing the study in additional 36 weeks, and when I say vast majority, we're talking about upwards of 90% of the eligible participants at week 36 that signed up for the open label extension.
That concludes today's question and answer session. I'd like to turn the call back to Ray Stevens for closing remarks.
Thank you all for joining us today. We look forward to keeping you updated as we advance Eleniglipron into Phase 3, our Amylin program, and our multiple combination programs. Have a nice day.
This concludes today's conference call. Thank you for participating. You may now disconnect.