aleniglipron (GSBR-1290) / Structure Therap - LARVOL DELTA

ACCESS Open-Label Extension Study - Following randomized 36-week period, evaluating lower 2.5mg starting dose (GlobeNewswire) - "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."

Clinical data • Obesity

Body Composition Study - Evaluating lower 2.5 mg starting dose (GlobeNewswire) - "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."

P2 data • Obesity

Phase 3 Preparation (GlobeNewswire) - "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."

New P3 trial • Obesity

Exploratory ACCESS II Study - Evaluating higher doses up to 240 mg (GlobeNewswire) - "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."

P2 data • Obesity

Phase 2b ACCESS study - Evaluating target doses of up to 120 mg (GlobeNewswire) - "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."

P2b data • Obesity

Structure Therapeutics…announced plans to release topline data from its ACCESS clinical program of aleniglipron, the company’s once-daily oral small molecule GLP-1 receptor agonist for the treatment of obesity, before the market opens on Monday, December 8, 2025 (GlobeNewswire)

P2 data • Obesity

Discovery and Nonclinical Profile of AMB-234, a Novel, Orally Bioavailable GLP-1 Receptor Agonist (OBESITY WEEK 2025) - "Where appropriate, benchmark compounds (orforglipron and aleniglipron) were included. The novel, orally available small molecule GLP-1 agonist, AMB-234, demonstrated subnanomolar potency with desirable ADME, pharmacokinetic properties and robust pharmacodynamic activity in transgenic humanized GLP-1R mice. These data showcase the potential of AMB-234 as a treatment for obesity, type 2 diabetes and other cardiometabolic disorders. Nonclinical studies to characterize AMB-234 in obesity models in mice are in progress."

Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Aleniglipron (GSBR-1290) - Oral Small Molecule Selective Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist for the Treatment of Obesity and Overweight (GlobeNewswire) - "ACCESS and ACCESS II Studies on track for topline 36-week data readouts by year-end 2025."

P2b data • Obesity

Aleniglipron Phase 2 Body Composition Study (clinicaltrials.gov) - P2 | N=71 | Active, not recruiting | Sponsor: Gasherbrum Bio, Inc., a wholly owned subsidiary of Structure Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

Aleniglipron Phase 2 Body Composition Study (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Gasherbrum Bio, Inc., a wholly owned subsidiary of Structure Therapeutics

New P2 trial • Genetic Disorders • Obesity

ACCESS: A Phase 2b, Dose-range Finding Study of the Efficacy and Safety of Multiple Doses of Aleniglipron (GSBR-1290) in Participants Living With Obesity or Overweight With at Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=220 | Active, not recruiting | Sponsor: Gasherbrum Bio, Inc., a wholly owned subsidiary of Structure Therapeutics | Trial completion date: Nov 2025 ➔ Aug 2026 | Trial primary completion date: Oct 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

Expanded Data Collection from ACCESS and ACCESS II Studies (GlobeNewswire) - "Structure Therapeutics has implemented extensions to the ongoing ACCESS and ACCESS II studies: (i) ACCESS Open Label Extension (OLE) - All patients in the Phase 2b ACCESS study are provided an option to roll over into the OLE and receive aleniglipron after completing the double-blinded randomized portion of the study. This will allow collection of data on longer-term weight loss effects, expand the overall safety database and provide aleniglipron access to patients enrolled in the blinded portion of the study who opt in to the extension; (ii) ACCESS II Extension - Following the initial 36-week efficacy evaluation, patients will now continue on their assigned dose to 44 weeks, which allows for collection of an additional eight weeks of double-blinded safety, tolerability, and efficacy data in the study....Per protocol and as previously planned, a formal unblinded efficacy assessment at 36 weeks is expected by year-end 2025."

P2 data • Trial status • Obesity

Three Additional Aleniglipron Studies (GlobeNewswire) - "(i) Phase 2 study to assess a maintenance switching strategy from an approved injectable GLP-1 receptor agonist to aleniglipron - Specifically, this maintenance switching study will evaluate the transition from an approved injectable GLP-1 receptor agonist to once-daily oral aleniglipron for weight loss maintenance. This study will assess the starting dose and the weight loss maintenance over 12 weeks. Enrollment is expected to start in the third quarter of 2025; (ii) Phase 2 body composition study - This study will assess the effect of aleniglipron on body fat loss over a 40-week evaluation period. These data will be used to incorporate body composition endpoints into the Phase 3 program. Enrollment is expected to start in the third quarter of 2025; (iii) Phase 2 study in patients with type 2 diabetes mellitus (T2DM) - This placebo-controlled study in patients with obesity or overweight and T2DM is anticipated to start in the fourth quarter of 2025."

New trial • Obesity • Type 2 Diabetes Mellitus

Structure Therapeutics Reports First Quarter 2025 Financial Results and Recent Highlights (GlobeNewswire) - "Recent and Upcoming Milestones: Aleniglipron (GSBR-1290); The Phase 2b ACCESS and ACCESS II studies are fully enrolled and on track for topline 36-week data by year-end 2025....ACCG-2671: Investigational new drug (IND) enabling activities for ACCG-2671 are ongoing; Structure Therapeutics plans to initiate a first-in-human Phase 1 clinical study by year-end 2025. New preclinical data for ACCG-2671 will be presented in a late-breaking poster session at the American Diabetes Association (ADA) 85th Scientific Sessions on June 22, 2025....Structure Therapeutics is evaluating ANPA-0073, a Phase 2 ready biased APJR agonist for potential selective or muscle-sparing weight loss....Long term chronic GLP-toxicology studies are currently underway and expected to be completed in 2025....Research and Development (R&D) Expenses: R&D expenses for the first quarter of 2025 were $42.9 million, as compared to $20.7 million for the same period in 2024."

Commercial • New P1 trial • P2b data • Preclinical • Trial completion date • Obesity

Current Insights, Advantages and Challenges of Small Molecule Glucagon-like Peptide 1 Receptor Agonists: A Scoping Review. (PubMed, J Brown Hosp Med) - "These small molecules offer enhanced tissue permeability, extended half-lives, and the potential for fixed-dose combinations, addressing limitations of injectable formulations. This review explores the preclinical and clinical progress of small-molecule GLP-1RAs, highlighting their potential to redefine diabetes care by improving convenience, adherence, and accessibility for patients."

Journal • Review • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

ACCESS: A Phase 2b, Dose-range Finding Study of the Efficacy and Safety of Multiple Doses of GSBR-1290 in Participants Living With Obesity or Overweight With at Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=220 | Active, not recruiting | Sponsor: Gasherbrum Bio, Inc., a wholly owned subsidiary of Structure Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

ACCESS II: A Dose-Range Study of GSBR-1290 in Participants Living With Obesity or Overweight With at Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=82 | Active, not recruiting | Sponsor: Gasherbrum Bio, Inc., a wholly owned subsidiary of Structure Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

ACCESS II: A Dose-Range Study of GSBR-1290 in Participants Living With Obesity or Overweight With at Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=82 | Recruiting | Sponsor: Gasherbrum Bio, Inc., a wholly owned subsidiary of Structure Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

ACCESS II: A Dose-Range Study of GSBR-1290 in Participants Living With Obesity or Overweight With at Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=82 | Not yet recruiting | Sponsor: Gasherbrum Bio, Inc., a wholly owned subsidiary of Structure Therapeutics

New P2 trial • Genetic Disorders • Obesity

ACCESS: A Phase 2b, Dose-range Finding Study of the Efficacy and Safety of Multiple Doses of GSBR-1290 in Participants Living with Obesity or Overweight with At Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=220 | Recruiting | Sponsor: Gasherbrum Bio, Inc., a wholly owned subsidiary of Structure Therapeutics

New P2 trial • Genetic Disorders • Obesity

Significant and Clinically Relevant Weight Changes at 12 Weeks With Small Molecule GLP-1RA,GSBR-1290 (OBESITY WEEK 2024) - "GSBR-1290 showed clinically meaningful and statistically significant BW reduction in participants with overweight or obesity, with a tolerability profile consistent with the GLP-1RA class. A phase 2b study will initiate by end of 2024."

Clinical • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Liver Failure • Obesity

Drug Design Principles and Pharmacokinetics/Pharmacodynamics of GSBR-1290, a Small Molecule GLP-1RA (OBESITY WEEK 2024) - "GSBR-1290 was designed with specific properties resulting in PK parameters supportive of QD dosing with broad safety margins. Modeling projects competitive long-term efficacy, with tolerance development to nausea and emesis over time, as observed with other GLP-1RAs."

PK/PD data

A phase 1, randomised, double-blind trial of the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral small molecule GSBR-1290 in Japanese and non-Japanese healthy volunteers (EASD 2024) - P1 | "GSBR-1290 demonstrated a favorable safety and tolerability profile in a group of healthy participants without clinical differences between Japanese and non-Japanese individuals. Additionally, both groups experienced weight reduction in this 4-week study. These data provide support to continue development of GSBR-1290 in a Japanese population."

Clinical • P1 data • PK/PD data • Metabolic Disorders • Type 2 Diabetes Mellitus

A Phase 1b/2a Study of the Safety and Tolerability of GSBR-1290, a Novel Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA), in Healthy Overweight/Obese Volunteers (HOV) and Participants with Type 2 Diabetes Mellitus (T2DM) (ADA 2024) - "GSBR-1290 demonstrated favorable safety and tolerability in this Phase 1b/2a study in participants with T2DM and in HOV. GSBR-1290 demonstrated clinical benefits in lowering BW, blood glucose, and HbA1c. These data provide clinical proof-of-concept of GSBR-1290 and support further clinical development in T2DM and obesity."

Clinical • P1/2 data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Phase 1b/2a Study of GSBR-1290 in Adult Overweight or Obese Healthy Subjects and Subjects With Type 2 Diabetes Mellitus (clinicaltrials.gov) - P1/2 | N=142 | Completed | Sponsor: Gasherbrum Bio, Inc | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus