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Structure announces positive results from oral GLP-1 receptor agonist gsbr-1290

Structure Therapeutics has 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 individuals living with obesity. In the 28-day study, GSBR-1290 demonstrated significant weight loss supporting once-daily (QD) dosing and an encouraging safety and tolerability profile.

GSBR-1290 is an orally-available, small molecule agonist of the glucagon-like-peptide-1 (GLP-1) receptor, a validated drug target for the treatment of type 2 diabetes and obesity. GSBR-1290 was designed through the company’s structure-based drug discovery platform and is designed to be a biased GPCR agonist, which selectively activates the G-protein signalling pathway.


“These positive Phase 1b results support GSBR-1290 as a promising, differentiated oral GLP-1 receptor agonist with once-daily dosing,” said Dr Raymond Stevens, Founder and CEO of Structure. “GSBR-1290 demonstrated an encouraging safety and tolerability profile with no adverse event-related discontinuations and we are encouraged by the weight loss observed following four weeks of treatment. We look forward to sharing results of GSBR-1290 over a longer 12-week period in the Phase 2a study, and we continue to move forward with all activities in order to begin Phase 2b clinical trials in both type 2 diabetes and obesity as planned in 2024.”


The Phase 1b MAD study focused on the safety and tolerability of GSBR-1290 in 24 healthy overweight or obese individuals. Participants were randomised 3:1 to GSBR-1290 or placebo across three dose cohorts with target doses of 30mg, 60mg or 90mg. GSBR-1290 demonstrated reductions in mean body weight ranging up to 4.9kg compared to baseline, and up to 4.9% placebo-adjusted (Table 1).

Table 1: Percent weight change from baseline to day 28

GSBR-1290 demonstrated an encouraging safety and tolerability profile following once-daily dosing. No participants discontinued the study drug due to adverse events. The majority of adverse events reported were mild, with no severe or serious adverse events observed. As expected for this class, leading adverse events were gastrointestinal-related, with the two most common adverse events being nausea and vomiting, with higher incidences observed in the 60 and 90 mg dose cohorts compared to placebo. There were no clinically meaningful changes in liver function tests.

Table 2: Summary of Treatment Emergent Adverse Events (TEAEs)

A data collection omission occurred at a clinical site that impacted the obesity cohort (120mg dose level) of the Phase 2a study, where weight was not collected at the final (week 12) visit for 24 of the 40 enrolled participants. Other safety and laboratory assessments were measured at all visits, including the week 12 visit as per protocol.

Structure will enrol additional participants in the Phase 2a obesity cohort to replace those for whom 12-week weight data was not collected. The replacement participants will follow the same study protocol, without changes in the titration schema or target dose (120 mg/QD). As a result, Structure now plans to report topline data from the obesity cohort in the first half of 2024. While Structure remains blinded to data from the Phase 2a obesity cohort, there were no adverse-event related discontinuations through the end of the study at 12 weeks for any of the 40 participants in the Phase 2a obesity cohort.


Structure remains on track to report topline data from the type 2 diabetes cohort of the Phase 2a study in the latter half of the fourth quarter of 2023 as planned, along with results from the Japanese ethno-bridging study of GSBR-1290.


Structure continues to plan to initiate two Phase 2b studies of GSBR-1290 in 2024. The type 2 diabetes study is expected to include approximately 500 individuals across the United States, Europe and Japan. The obesity study is expected to include approximately 275 individuals across the United States and Europe.


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. Pending supportive data from this bridging study, the tablet formulation would be used in future GSBR-1290 studies starting with the planned Phase 2b studies.


Beyond GSBR-1290, Structure is developing next generation combination GLP-1R candidates, including dual GLP-1R/GIPR agonists and amylin agonists, each designed with customized properties to achieve additional benefits.

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