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

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

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=144 | Active, not recruiting | Sponsor: Gasherbrum Bio, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study of Multiple-ascending Doses of GSBR-1290 in Healthy Overweight/Obese Participants (clinicaltrials.gov) - P1 | N=70 | Active, not recruiting | Sponsor: Gasherbrum Bio, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Obesity

A Study of Multiple-ascending Doses of GSBR-1290 in Healthy Overweight/Obese Participants (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Gasherbrum Bio, Inc

Trial completion date • Trial primary completion date • Obesity

Structure Therapeutics Provides Comprehensive GSBR-1290 Program Update Including Clinically Meaningful Proof-of-Concept Data From Phase 2a Clinical Study (GlobeNewswire) - P1 | N=18 | NCT05893043 | Sponsor: Gasherbrum Bio, Inc | "GSBR-1290 demonstrated a substantial weight reduction in Japanese participants (-3.91% on GSBR-1290 vs -1.67% placebo) and in non-Japanese participants (-5.13% not placebo-adjusted), with no discontinuations or dose reductions, and no SAEs. These data will be used for regulatory interactions in Japan in preparation for potential future global studies of GSBR-1290....Structure has completed 6-month (rodent) and 9-month (non-human primate) toxicology studies to evaluate the safety of GSBR-1290. No major findings were observed in either study, with no test article-related changes observed in the liver, including ALT/AST, at all doses, and a >100 fold safety window at the 120 mg therapeutic dose."

P1 data • Preclinical • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Structure Therapeutics Provides Comprehensive GSBR-1290 Program Update Including Clinically Meaningful Proof-of-Concept Data From Phase 2a Clinical Study (GlobeNewswire) - P2a | N=118 | NCT05762471 | Sponsor: Gasherbrum Bio, Inc | "Structure Therapeutics Inc...provided a comprehensive development program update for its highly selective oral GLP-1 receptor agonist, GSBR-1290....'We are pleased that we have achieved the objectives of our first Phase 2a clinical trial of GSBR-1290 in T2DM patients which were to demonstrate favorable safety, tolerability and efficacy results and guide our plans to further optimize the already encouraging performance of GSBR-1290'...In the T2DM cohort, there was a statistically significant HbA1c reduction (- 1.01 to -1.02%, placebo-adjusted) at Week 12. The study demonstrated a statistically significant and clinically meaningful reduction in weight at Week 12 (-3.26% to -3.51%, placebo-adjusted) (Table 3). Weight loss continued to decrease through Week 12."

P2a data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Structure Therapeutics Provides Comprehensive GSBR-1290 Program Update Including Clinically Meaningful Proof-of-Concept Data From Phase 2a Clinical Study (GlobeNewswire) - "Full 12-week results from the Phase 2a obesity cohort (n=64), including data from the additional 24 participants currently being enrolled, are expected in the second quarter of 2024. Structure plans to initiate a Phase 2b obesity study of GSBR-1290 in the second half of 2024. The study is planned to include at least 275 individuals across the United States and Europe and will include multiple modified dose titration regimens to optimize efficacy and tolerability. An additional Phase 2 study in T2DM is also planned for the second half of 2024 to optimize the efficacy and tolerability of GSBR-1290 in this patient population. The ongoing formulation bridging and titration optimization study is evaluating capsule versus tablet pharmacokinetics (PK) and exploring different titration regimens. This study has completed enrollment (n=54), and data are expected in the second quarter of 2024."

New P2 trial • New P2b trial • P1 data • P2a data • PK/PD data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study of Multiple-ascending Doses of GSBR-1290 in Healthy Overweight/Obese Participants (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Gasherbrum Bio, Inc

New P1 trial • Obesity

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=118 | Recruiting | Sponsor: Gasherbrum Bio, Inc | Active, not recruiting ➔ Recruiting | Phase classification: P1b/2a ➔ P1/2 | Trial completion date: Dec 2023 ➔ Mar 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Enrollment open • Phase classification • Trial completion date • Trial primary completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Structure Therapeutics Announces $300 Million Private Placement Equity Financing (GlobeNewswire) - "Structure Therapeutics Inc...today announced it has entered into a share purchase agreement for the sale of 21,617,295 ordinary shares and 2,401,920 newly designated non-voting ordinary shares...at $12.49 per share (based on the closing price of $37.47 per ADS on September 28, 2023) through a private placement financing....'We plan to use the net proceeds from this financing to accelerate GSBR-1290 development and our earlier programs from our broad oral incretin franchise forward, including our next-generation GLP-1/GIPR combination and our promising oral small molecule amylin receptor agonist. We expect to deliver development candidates for both programs in 2024.'"

Financing • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Structure Therapeutics Announces Positive Results from Phase 1b Clinical Study of Oral GLP-1 Receptor Agonist GSBR-1290 and Provides Program Update (GlobeNewswire) - P1 | N=24 | "Structure Therapeutics Inc...announced positive results from the Phase 1b multiple ascending dose (MAD) study of its highly selective oral GLP-1 receptor agonist, GSBR-1290, in healthy overweight or obese individuals....GSBR-1290 demonstrated reductions in mean body weight ranging up to 4.9 kg compared to baseline, and up to 4.9% placebo-adjusted....A data collection omission occurred at a clinical site that impacted the obesity cohort (120 mg dose level) of the Phase 2a study....As a result, Structure now plans to report topline data from the obesity cohort in the first half of 2024....In preparation for the Phase 2b studies, Structure is also planning a separate formulation bridging PK study to support the planned transition from capsules to tablets, which is expected to initiate in the fourth quarter of 2023 and complete in the second quarter of 2024."

New trial • P1 data • P2a 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) - P1b/2a | N=118 | Active, not recruiting | Sponsor: Gasherbrum Bio, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus