Structure Therapeutics Reports Positive Topline

Structure Therapeutics Reports Positive Topline

Data from ACCESS Program for its Once-Daily Oral Small Molecule GLP-1 Receptor Agonist, Aleniglipron

Placebo-adjusted mean weight loss of 11.3% (27.3

lbs) with 120 mg dose in the 36-week Phase 2b ACCESS study with a 10.4% adverse event-related treatment discontinuation

Placebo-adjusted mean weight loss up to 15.3%

(35.5 lbs) observed with 240 mg dose in the exploratory ACCESS II study at 36 weeks

No adverse event-related treatment discontinuations

observed when starting at lower 2.5 mg dose in ACCESS Open Label Extension and Body Composition Study

Data comprehensively support and inform advancement

to Phase 3 clinical development program in mid-2026

Company to host conference call today at 8:30

SAN FRANCISCO, December 8, 2025-

Structure Therapeutics Inc. (NASDAQ: GPCR), a clinical-stage global biopharmaceutical company developing novel oral small molecule

therapeutics for metabolic diseases, with a focus on obesity, today announced positive topline data from the ACCESS clinical program of

aleniglipron for the treatment of people living with obesity and/or overweight with at least one weight related co-morbidity. This includes

36-week data from the core Phase 2b ACCESS study and the ongoing exploratory ACCESS II study, and interim data from the ongoing Body Composition

study and the ACCESS open label extension (OLE) study. Aleniglipron is an investigational orally-available, once-daily, nonpeptide small

molecule agonist of the glucagon-like-peptide-1 (GLP-1) receptor designed to address patient needs and accessibility.

In the core Phase 2b ACCESS study, aleniglipron achieved a clinically

meaningful and statistically significant placebo-adjusted mean weight loss of 11.3% (27.3 lbs, p<0.0001) at the 120 mg dose at 36 weeks

and across all active arms had a 10.4% adverse event (AE)-related treatment discontinuation rate. In the exploratory ACCESS II study,

aleniglipron achieved a placebo-adjusted mean weight loss up to 15.3% (35.5 lbs, p<0.0001) with 240 mg dose at 36 weeks. Aleniglipron

demonstrated a tolerability profile consistent with the GLP-1 receptor agonist class, and a compelling off-target safety profile. Together,

these positive findings support the advancement of aleniglipron into Phase 3 clinical development.

"The topline results presented today show that aleniglipron is

differentiated and delivered clinically meaningful, competitive and dose-dependent weight loss with a safety profile appropriate for chronic

use in a disease that impacts millions of people," said Raymond Stevens, Ph.D., CEO of Structure Therapeutics. "For the higher

doses, the observed weight loss data at 36 weeks with no weight loss plateau is potentially best-in-class for oral small molecule GLP1s.

Most importantly, these findings provide comprehensive information to move into Phase 3 development and reinforce aleniglipron's

potential to become a backbone oral small molecule therapy for obesity-one that is accessible, scalable, and combinable."

"The weight-lowering data from these ACCESS studies, without

any evidence of a plateau by Week 36, are very encouraging-particularly weight loss of up to 15.3% in ACCESS II that hopefully will

be confirmed in larger, longer-term studies," said Julio Rosenstock, MD, Chair of the ACCESS program Steering Committee and Senior

Scientific Advisor of Velocity Clinical Research and Clinical Professor of Medicine, Univ. of Texas, Southwestern Medical Center. "As

once-daily oral, non-peptide, small molecule GLP-1 RAs such as aleniglipron become available, they have the potential to transform obesity

treatment and broaden access, which could have a profound impact on patients globally."

"Obesity is a complex, chronic disease, and far too many individuals

still face barriers to accessing effective, long-term treatment options," said Joe Nadglowski, Obesity Action Coalition President

and CEO. "A once-daily oral therapy like aleniglipron has the potential to expand treatment options for people living with obesity.

The results from the ACCESS programs represent a promising advance in the therapeutic landscape and bring us closer to a future where

people living with obesity have multiple, accessible options to address their needs."

Phase 2b ACCESS study - Evaluating target doses of up to 120

The core 36-week Phase 2b ACCESS study was a randomized, double-blind,

placebo-controlled, Phase 2b dose-range finding clinical study that enrolled 230 adult participants living with obesity (body mass index

(BMI) 30 kg/m2), or overweight (BMI 27 kg/m2) with at least one weight-related comorbidity. All participants were randomized

3:1 (active:placebo) and started at 5 mg of aleniglipron (or placebo) with a 4-week titration schedule, reaching target doses of 45 mg,

90 mg or 120 mg once-daily.

Each of the three doses in the ACCESS study achieved statistical significance

on the primary endpoint and all key secondary endpoints. Primary efficacy estimandi results at 36 weeks are as follows:

At Week 36, key secondary endpoints in the study show that 86% of participants

in the aleniglipron 120 mg dose cohort achieved at least 5% weight loss and 70% achieved at least 10% weight loss. In addition, aleniglipron

demonstrated clinically meaningful improvements in systolic blood pressure (-6.4 to -7.5 mmHg) and HbA1c (-0.28% to -0.37%).

Aleniglipron demonstrated a tolerability profile consistent with the

GLP-1 receptor agonist class following repeated, once-daily dosing of up to 120 mg in the Phase 2b ACCESS study. As expected for the

GLP1-RA drug class, the most common AEs were gastrointestinal (GI)-related and the two most common AEs in the titration phase were nausea

and vomiting. AEs were generally observed early in treatment. In the Phase 2b ACCESS study, the AE-related treatment discontinuation rate

ranged from 7.7% - 13.3% between all doses, with a mean 10.4% across all active arms in the study.

Exploratory ACCESS II Study - Evaluating higher doses up to 240

ACCESS II is a randomized, double-blind, placebo-controlled, clinical

study of aleniglipron that enrolled 85 adult participants living with obesity, or overweight with at least one weight-related comorbidity.

The study was designed to evaluate two higher doses of aleniglipron. Participants started at 5 mg of aleniglipron (or placebo) and followed

a 4-week titration schedule up to target doses of 120 mg, 180 mg and 240 mg. The 44-week study remains ongoing, with data from a prespecified

36-week analysis currently available.

At 36 weeks, each of the three dose cohorts in the ACCESS II study

met statistical significance compared to placebo. Primary efficacy estimand results at 36 weeks are as follows:

Aleniglipron demonstrated a tolerability profile consistent with the

GLP-1 receptor agonist class following repeated, once- daily dosing of up to 240 mg. As expected for the GLP1-RA drug class, the most

common AEs were GI-related and the two most common AEs in the titration phase were nausea and vomiting. AEs were generally

observed early in treatment.

Body Composition Study - Evaluating lower 2.5 mg starting dose

Structure Therapeutics is currently conducting a randomized, placebo-controlled

body composition study that enrolled 71 adult participants to assess the effect of aleniglipron (up to 120 mg) on body fat loss over a

40-week evaluation period. Participants in the aleniglipron treatment arm start at a 2.5 mg dose, and titrate up monthly to a target dose

of 120 mg. Data from a pre-specified interim analysis after a median follow-up time of approximately 10 weeks showed that starting at

a lower dose of 2.5 mg for the first four weeks meaningfully improved tolerability compared to what was observed at a starting titration

dose of 5 mg in the ACCESS and ACCESS II studies, with no AE-related treatment discontinuations observed at the initial 2.5 mg dose or

the subsequent 5 mg dose.

ACCESS Open-Label Extension Study - Following randomized 36-week

period, evaluating lower 2.5mg starting dose

Following the 36-week randomized controlled portion of the Phase

2b ACCESS study, the majority of eligible ACCESS participants enrolled in ACCESS OLE. An initial analysis from the ongoing OLE

demonstrates continuing weight loss in all dose cohorts out to 44 weeks, showing no evidence of weight loss plateau.

In the ACCESS OLE, participants who received

placebo in the initial double-blind portion transitioned to aleniglipron at a starting dose of 2.5 mg and titrate monthly to a target

dose of 120 mg. Initial data from this group of participants after eight weeks of treatment are consistent with the findings from

the body composition study, showing that starting at a 2.5 mg titration dose meaningfully improved tolerability compared to what was observed

in the starting 5 mg titration dose in ACCESS and ACCESS II studies, with no AE-related treatment discontinuations at the initial 2.5

mg or the subsequent 5 mg dose.

Aleniglipron demonstrated a compelling safety profile across all studies.

Importantly, there were no cases of drug-induced liver injury, no persistent liver enzyme elevations, and no QTc prolongation across all

aleniglipron studies.

Data from ACCESS, ACCESS II, body composition,

and the ACCESS OLE studies provide a strong foundation to advance aleniglipron into Phase 3 clinical development. The Company plans to

request a Type B End-of-Phase 2 meeting with the United States Food and Drug Administration (FDA) in the first half of 2026 to finalize

the Phase 3 design, which is currently designed with a starting titration dose of 2.5 mg with the intent to evaluate multiple doses up

to 240 mg. Structure Therapeutics anticipates initiating the Phase 3 program by mid-2026.

Conference Call and Webcast Information

Structure Therapeutics will host a conference