Structure Therapeutics Inc. American Depositary Shares Study result

Thank you, and good morning. Earlier today, we issued a press release providing data updates from ACCG-2671, our oral small molecule dual amylin and calcitonin receptor agonist, and aleniglipron ACCESS open label extension results. A copy of the press release and the presentation accompanying today's call are available in the investor relations section of Structure Therapeutics website. I would like to remind everyone that some of the statements we will make on this call and information presented in the slide deck may 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 this slide, as well as our SEC filings for a more detailed description of the risk and 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, Tuesday, September 8th, 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 Ray Stevens, the Chief Executive Officer of Structure.

Good morning, everyone. On behalf of Structure Therapeutics, thank you for joining us today to discuss the important progress we're making across our oral small molecule portfolio for chronic weight management and to make medicines more accessible to all. We have two significant updates to report today, both equally exciting and important to addressing the unmet needs of patients' accessibility in chronic weight management. Following my opening remarks, Dr. Blai Coll, our Chief Medical Officer, will review both clinical programs in detail. After Dr. Coll's presentation, I will make some concluding remarks about the exciting opportunities in combination treatments for quality of life improvements, and then turn the call over to Q&A. Obesity treatment has advanced significantly, but the scale of unmet need remains extraordinary. Today, fewer than 1% of the addressable global population is receiving a branded anti-obesity medication.

That means the overwhelming majority of people who could benefit from treatment are still not being reached. This is not just the U.S. market. We are seeing significant importance of outside the U.S. market as well. Access is a major part of the challenge. Patients also have different treatment goals, tolerability needs, and journeys through long-term weight management. No single medicine will meet all of those needs. The next phase of the market will be oral medicines, which will be more accessible globally, provide more flexible treatment approaches, and support patients at different stages of their journey. The early response to oral GLP-1 medicines reinforces the level of demand for convenient oral treatment. Since oral Wegovy launched in January 2026, oral GLP-1s have grown more than 1.4 million U.S. patients and approximately 17% of the anti-obesity medication market, and that share continues to rise.

Importantly, approximately 80% of total prescriptions are coming from treatment-naïve patients. This suggests oral medicines are not simply shifting patients from one treatment to another. They are expanding the market and bringing new patients into treatment. Based on our market research, oral therapies could represent approximately half of the market by 2030. For a global population measured in the billions, scalability matters. We believe oral small molecules offer the manufacturing scale, convenience, and access needed to reach far more patients and support chronic treatment over time. We have the platform based on oral small molecules to offer manufacturing at the scale needed. With that unmet need clearly laid out, as we stated we would deliver in Q3, today we will focus on two very exciting programs that demonstrate the productivity and breadth of our structure-based drug discovery platform. Our amylin ACCG-2671 and our GLP-1 receptor agonist, aleniglipron.

Choosing which program to present first was not an easy decision, reflecting both the strength of these programs and our enthusiasm for their potential. On the left side, we'll begin with ACCG-2671, a first-in-class oral small molecule amylin receptor agonist, now in a phase I/IIa multiple ascending dose clinical trial. This is an extraordinary molecule, as we are the first to report clinical results of an oral small molecule amylin agonist. In the first-in-human single ascending dose study, we observed approximately six-day half-life, providing the potential for convenient daily or once-weekly dosing. ACCG-2671 demonstrated a clean safety profile with no serious adverse events or liver signals. In a clear dose response with the expected on-target gastrointestinal tolerability. Additionally, we observed encouraging exploratory effects on weight loss and bone health biomarkers as additional indicators of target engagement.

On the right side, aleniglipron is our oral small molecule selective GLP-1 receptor agonist, currently dosing in two global phase III trials. Today, we report the results from the ACCESS open label extension study that is now completed. We observed a potential best-in-class 16.2% body weight loss at 72 weeks, with room for potential additional weight loss with longer 52-week exposure at the 180 milligram dose as designed into the phase III program. Importantly, this potential best-in-class efficacy was accompanied by improved tolerability with a 2.5 milligram start, very low, less than 5%, adverse event-related discontinuation rate, and no off-target safety signal seen in over 800 participants across multiple dose levels up to 72 weeks. For a medicine that may be taken by millions of people around the world, safety is paramount, and we are very pleased with the very attractive safety profile of aleniglipron.

We're excited to have initiated our phase III ACCOMPLISH-1 and ACCOMPLISH-2 trials that are now underway and expected to read out in the second half of 2028. Together, these programs highlight the ability of our platform to generate differentiated oral medicines across complementary mechanisms while giving us meaningful optionality in combinations as we build our oral small molecule portfolio for chronic weight management. With that context, let me turn the call over to Dr. Blai Coll, our Chief Medical Officer, to present details on our amylin and GLP-1 oral small molecule data.

Thank you, Ray, and good morning, everyone. I will begin with ACCG-2671, our oral small molecule amylin receptor agonist. I'm excited to share the first clinical observations from the single ascending dose study. To understand why we believe this molecule is differentiated, let me start with the receptor biology. Amylin signaling is mediated through the calcitonin receptor combined with different Receptor Activity-Modifying Proteins or RAMPs, creating the amylin 1 through amylin 3 receptor subtypes. Amylin biology extends beyond modulation of appetite alone. In the central nervous system, it influences satiety, leptin sensitivity, and energy expenditure, contributing to beneficial effects on body weight regulation. It also affects the GI tract, adipose tissue, and insulin and glucagon secretion. In addition, the biology of a dual amylin and calcitonin receptor agonist or DACRA provides potentially positive effects on bone turnover via the calcitonin receptor.

CTX-1 is a marker of osteoclast activity that promotes bone resorption and is associated with potential deleterious effects in bone mass. Inversely, bone specific alkaline phosphatase is a marker of osteoblast activity, and its increase is associated with bone production. Dual amylin and calcitonin receptor agonists have been associated with a significant decrease in CTX-1 and correlated with an increase in bone specific alk phos. This broader biology provides several opportunities to explore target engagement, including early changes in body weight and bone resorption biomarkers that will be addressed in subsequent slides. 2671 was designed as an oral small molecule with broad activity across the human calcitonin receptor and all three amylin receptor subtypes, which characterizes it as a full dual amylin and calcitonin receptor agonist or DACRA. It demonstrates high binding affinity and functional activity in vitro, together with robust reductions in food intake and body weight in rodents.

Additionally, as you can see on the right-hand side of the slide and presented at ADA this summer, the preclinical activity established a clear dose response reduction in body weight. These were important results since they achieved significant levels of activity and supported advancement into clinical development, as described in the next slide. We evaluated ACCG-2671 in a phase I single ascending dose study in adult participants with BMI below 30, where 31 were randomized across the 1, 2, 5, and 10 milligram cohorts with a 3 to 1 allocation to active treatment and placebo. The primary objectives in this first human trial were pharmacokinetics, safety, and tolerability after a single oral dose with exploratory assessment of changes in body weight and bone biomarkers.

Let me reiterate here that the main objective of the single dose is to understand the PK, safety, and tolerability across a wide range of doses and inform the design of the Multiple Ascending Dose. In the single ascending dose, the follow-up extended to day 17 for the 1 through 5 milligram cohorts and day 24 for the 10 milligram cohort. We were pleased to not need to evaluate the 20 milligram cohort since the emerging clinical data and PK modeling supported moving directly into the phase IIa. Let me now provide the characteristics of the participants included in the analysis. The single ascending dose cohorts were generally comparable. All participants receiving ACCG-2671 completed treatment and the study. Mean age ranged from approximately 34 to 44 years.

Mean BMI was between 26 and 27 kilograms per square meter, indicating healthy participants not living with obesity, and women represented 50%-80% of the active dose cohort. 7 out of 8 pooled placebo participants completed the study. Let's now review the pharmacokinetic properties of ACCG-2671. The pharmacokinetic profile of the molecule is well-suited for further development. We are sharing two PK curves here. On the left is the linear ACCG-2671 concentration time profile following single oral dose administration across the dose range of 1 to 10 mgs for the first 24 hours, and illustrates the rapid absorption of ACCG-2671, with maximum concentration reaching approximately 1 to 1.5 hours.