Structure Therapeutics Reports Positive Topline Data from ACCESS Program for its Once-Daily Oral Small Molecule GLP-1 Receptor Agonist, Aleniglipron

Rhea-AI Summary

Structure Therapeutics (NASDAQ: GPCR) reported positive 36‑week topline results for oral GLP‑1 receptor agonist aleniglipron from the ACCESS program supporting Phase 3 entry by mid‑2026. In the Phase 2b ACCESS study aleniglipron 120 mg produced a placebo‑adjusted mean weight loss of 11.3% (27.3 lbs) at 36 weeks (p<0.0001) with AE‑related discontinuations ranging 7.7%–13.3% (mean 10.4%) across active arms. In exploratory ACCESS II, the 240 mg dose achieved placebo‑adjusted mean weight loss up to 15.3% (35.5 lbs) at 36 weeks (p<0.0001). Studies reported GLP‑1 class GI adverse events, no drug‑induced liver injury, no persistent liver enzyme elevations, and no QTc prolongation. Company plans an FDA Type B meeting in H1 2026 and to start Phase 3 by mid‑2026.

Positive

• Placebo‑adjusted weight loss −11.3% at 120 mg (36 weeks)
• Placebo‑adjusted weight loss −15.3% at 240 mg (36 weeks) in ACCESS II
• No drug‑induced liver injury or persistent liver enzyme elevations reported
• No QTc prolongation observed across studies
• Phase 3 planned with FDA Type B meeting targeted H1 2026; start mid‑2026
• Lower 2.5 mg titration improved tolerability with no AE‑related discontinuations at initial doses

Negative

• AE‑related discontinuation 7.7%–13.3% across active arms (mean 10.4%) in Phase 2b
• Most common AEs were GI‑related (nausea and vomiting) observed early in treatment

Key Figures

Weight loss 120 mg 11.3% (27.3 lbs) placebo-adjusted at 36 weeks Phase 2b ACCESS, 120 mg dose

Weight loss 240 mg 15.3% (35.5 lbs) placebo-adjusted at 36 weeks Exploratory ACCESS II, 240 mg dose

≥5% weight loss 86% of participants ACCESS 120 mg cohort at Week 36

≥10% weight loss 70% of participants ACCESS 120 mg cohort at Week 36

AE discontinuations 10.4% mean across active arms ACCESS Phase 2b study up to 120 mg

Blood pressure change -6.4 to -7.5 mmHg Systolic blood pressure improvement at Week 36

HbA1c change -0.28% to -0.37% Glycemic control improvement in ACCESS

Discontinuations at 2.5 mg 0 AE-related discontinuations Body composition and OLE, 2.5–5 mg titration

Market Reality Check

$34.56 Last Close

Volume Volume 1,170,208 is 0.92x the 20-day average of 1,270,968 normal

Technical Price $34.56 is trading above the 200-day MA at $23.48

Peers on Argus

GPCR gained 5.21% while close peers showed mixed, smaller moves (e.g., ELVN +1.77%, NUVB +2.64%, PGEN -5.01%), indicating a stock-specific reaction.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 06	Earnings and pipeline	Positive	+3.9%	Reported strong cash of $799M and reaffirmed upcoming aleniglipron readouts.
Sep 02	Investor conferences	Positive	+4.0%	Announced participation in major healthcare investor conferences with webcasts.
Aug 06	Earnings and pipeline	Neutral	-0.7%	Detailed Q2 financials and progress toward topline aleniglipron data by year-end.
Jun 20	Clinical trial data	Positive	+1.7%	Presented preclinical obesity and Parkinson’s data at ADA late-breaking posters.

Pattern Detected

Recent news events, including earnings, conferences, and clinical updates, have generally seen modest positive share reactions, suggesting investors have rewarded pipeline progress and visibility.

Recent Company History

Over the last six months, Structure Therapeutics has highlighted steady progress across its metabolic pipeline. Earnings updates on 08/06 and 11/06/2025 emphasized cash of $786.5M–$799.0M funding operations into 2027 while preparing key obesity programs, including aleniglipron and oral amylin agonists. A clinical-focused ADA presentation on 06/20/2025 and conference participation on 09/02/2025 underscored increasing scientific visibility. Today’s positive Phase 2b aleniglipron data represents the anticipated efficacy inflection that prior updates had been building toward.

Regulatory & Risk Context

Active S-3 Shelf Registration 2025-08-06

The company has an effective S-3ASR shelf registration dated 2025-08-06, expiring on 2028-08-06, with 0 reported takedowns so far. This provides pre-cleared flexibility to issue securities in the future without indicating any specific transaction size or timing.

Market Pulse Summary

This announcement highlights robust Phase 2b and exploratory ACCESS data for aleniglipron, including placebo-adjusted weight loss up to 15.3% at 36 weeks, meaningful blood pressure and HbA1c improvements, and improved tolerability with a 2.5 mg starting dose. Historically, GPCR’s clinical news, such as the 06/20/2025 update, has been viewed constructively. Investors may watch for the planned FDA Type B End-of-Phase 2 meeting, Phase 3 design details, and how the company utilizes its effective S-3ASR shelf over time.

Key Terms

glp-1 receptor agonist medical

"once-daily oral small molecule GLP-1 receptor agonist, aleniglipron"

A GLP-1 receptor agonist is a medicine that mimics a natural gut hormone to trigger insulin release, slow stomach emptying, and curb appetite — like using a key to turn on a lock that controls blood sugar and hunger signals. For investors, these drugs matter because they treat common conditions such as diabetes and obesity, can drive large prescription and sales growth, reshape healthcare costs, and heavily affect drug pipelines, competition and company valuations.

phase 2b medical

"the 36-week Phase 2b ACCESS study with a 10.4% adverse event-related"

Phase 2b is a stage in the development of a new medicine or treatment where researchers test its effectiveness and safety in a larger group of people. This step helps determine whether the treatment works well enough to move forward and if it has manageable side effects, which is important for investors because successful results can lead to potential approval and market opportunity.

hba1c medical

"improvements in systolic blood pressure (-6.4 to -7.5 mmHg) and HbA1c (-0.28% to -0.37%)"

A1c (HbA1c) is a blood test that measures how much sugar has stuck to red blood cells over the past two to three months, giving a single number that reflects average blood glucose control—think of it as a running average score for blood sugar. Investors watch A1c because it’s a common clinical measure used to judge whether diabetes drugs, devices or care programs work, influence regulatory approvals, treatment guidelines and market demand.

AI-generated analysis. Not financial advice.

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 a.m. Eastern Time

SAN FRANCISCO, Dec. 08, 2025 (GLOBE NEWSWIRE) -- 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 mg
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:

	Aleniglipron 45 mg	Aleniglipron 90 mg	Aleniglipron 120 mg	Placebo
Mean percent change in body weight at 36 weeks compared to baseline	-9.0	-10.7	-12.1	-0.8
Placebo-adjusted mean percent change in body weight at 36 weeks compared to baseline	-8.2	-9.8	-11.3	-
P-value	p<0.0001	p<0.0001	p<0.0001	-

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 mg
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 120 mg	Aleniglipron 180 mg	Aleniglipron 240 mg	Placebo
Mean percent change in body weight at 36 weeks compared to baseline	-13.1	-13.3	-14.2	+1.0
Placebo-adjusted mean percent change in body weight at 36 weeks compared to baseline	-14.1	-14.4	-15.3	-
P-value	p<0.0001	p<0.0001	p<0.0001	-

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 Safety
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.

Phase 3 Preparation
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 call and webcast today, December 8, 2025 at 8:30 a.m. Eastern Time. A live webcast of the call will be available on the Investor Relations page of Structure Therapeutics’ website at https://ir.structuretx.com/events-presentations/events. To access the call by phone, participants should visit this link to receive dial-in details. The webcast will be made available for replay on Structure Therapeutics’ website beginning approximately two hours after the live event. The replay of the webcast will be available for 90 days.

About Aleniglipron and Structure Therapeutics’ Oral Metabolic Franchise
Aleniglipron (GSBR-1290) is an investigational orally-available, small molecule agonist of the glucagon-like-peptide-1 (GLP-1) receptor, a validated drug target for the treatment of obesity and type 2 diabetes mellitus (T2DM). Through Structure Therapeutics’ structure-based drug discovery platform, aleniglipron was designed to be a biased G Protein-Coupled Receptor (GPCR) agonist, which selectively activates the G-protein signaling pathway. Beyond aleniglipron, Structure Therapeutics is developing next generation oral small molecules including amylin receptor agonists, and other combination GLP-1 receptor agonists candidates such as glucose-dependent insulinotropic polypeptide (GIP), glucagon and apelin oral small molecules.

About Structure Therapeutics
Structure Therapeutics is a science-driven clinical-stage biopharmaceutical company focused on discovering and developing innovative oral small molecule treatments for chronic metabolic conditions with significant unmet medical needs. Utilizing its next generation structure-based drug discovery platform, the Company has established a robust GPCR-targeted pipeline, featuring multiple wholly-owned proprietary clinical-stage oral small molecule compounds designed to surpass the scalability limitations of traditional biologic and peptide therapies and be accessible to more people living with obesity around the world. For additional information, please visit www.structuretx.com.

Forward Looking Statements
This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical fact are statements that could be deemed forward-looking statements, including, without limitation, statements concerning: the Company’s future plans and prospects; any expectations regarding the potential benefits, tolerability and safety profile, accessibility, scalability, combinability, capability, efficacy, convenience, expected effects and future application of aleniglipron; the belief that data to date from the Phase 2b ACCESS, Phase 2 ACCESS II, body composition, and the Phase 2b ACCESS OLE studies support and inform advancement of the Phase 3 clinical development of aleniglipron; the belief that aleniglipron represents a potentially best-in-class small molecule GLP1 and may be a backbone therapy for obesity; the expected timing for the meeting with the FDA to finalize the Phase 3 trial design and the Phase 3 program initiation of aleniglipron; any presumption that topline, interim or preliminary data will be representative of final data or data in later clinical trials; and the belief that the results from ACCESS program represent a promising advance in the therapeutic landscape and brings the Company closer to a future where people living with obesity have multiple, accessible options to address their needs. In addition, when or if used in this press release, the words and phrases “anticipated,” “believe,” “expect,” “may,” “on track,” “plan,” “potential,” “suggests,” “to be,” “to begin,” “will,” and similar expressions and their variants, as they relate to the Company may identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Although the Company believes the expectations reflected in such forward-looking statements are reasonable, the Company can give no assurance that such expectations will prove to be correct. Readers are cautioned that actual results, levels of activity, safety, performance or events and circumstances could differ materially from those expressed or implied in the Company’s forward-looking statements due to a variety of risks and uncertainties, which include, without limitation: risks and uncertainties related to topline results that the Company reports are based on preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and such topline data may not accurately reflect the complete results of a clinical trial, the preliminary nature of the results due to the length of the study and sample size and the results from earlier clinical studies not necessarily being predictive of future results; potential delays in the commencement, enrollment and completion of the Company’s planned clinical studies; the Company’s ability to advance aleniglipron, ACCG-2671, ACCG-3535, ANPA-0073, LTSE-2578, and its other therapeutic candidates, obtain regulatory approval of, and ultimately commercialize the Company’s therapeutic candidates; competitive products or approaches limiting the commercial value of the Company’s product candidates; the timing and results of preclinical and clinical studies; the Company’s ability to fund development activities and achieve development goals; the Company's reliance on third parties, including clinical research organizations, manufacturers, suppliers and collaborators, over which it may not always have full control; general geopolitical and macroeconomic conditions, including as a result of tariffs and various global conflicts; the Company’s ability to protect its intellectual property; and other risks and uncertainties described in the Company’s filings with the Securities and Exchange Commission (SEC), including the Company’s latest Quarterly Report on Form 10-Q and future reports the Company may file with the SEC from time to time. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Investors:
Danielle Keatley
Structure Therapeutics Inc.
ir@structuretx.com

Media:
Dan Budwick
1AB
Dan@1abmedia.com

_________________________
ⁱ The primary efficacy estimand represents efficacy had all randomized participants remained on study treatment (with possible dose interruptions and/or dose modifications) for 36 weeks without initiating rescue weight management treatments or surgeries.

FAQ

What weight loss did Structure Therapeutics report for GPCR aleniglipron 120 mg at 36 weeks?

The Phase 2b ACCESS study reported a placebo‑adjusted mean weight loss of 11.3% (27.3 lbs) at 36 weeks for the 120 mg dose (p<0.0001).

How much weight loss did GPCR aleniglipron 240 mg achieve in ACCESS II at 36 weeks?

The exploratory ACCESS II study reported a placebo‑adjusted mean weight loss up to 15.3% (35.5 lbs) at 36 weeks for the 240 mg dose (p<0.0001).

What safety signals did Structure Therapeutics report for GPCR aleniglipron across studies?

Studies reported class‑consistent GI AEs (nausea, vomiting), no drug‑induced liver injury, no persistent liver enzyme elevations, and no QTc prolongation.

What was the discontinuation rate for GPCR aleniglipron in the Phase 2b ACCESS study?

AE‑related treatment discontinuation ranged from 7.7% to 13.3% across active doses, averaging 10.4%.

How will Structure Therapeutics start titration in Phase 3 for GPCR aleniglipron?

Phase 3 is currently designed to start with a 2.5 mg titration dose with plans to evaluate multiple doses up to 240 mg.

When does Structure Therapeutics plan to begin Phase 3 for GPCR aleniglipron?

The company anticipates initiating the Phase 3 program by mid‑2026 after a Type B End‑of‑Phase 2 meeting with FDA in H1 2026.