Structure Therapeutics Reports Positive Topline Data from its Phase 2a Obesity Study and Capsule to Tablet PK Study for its Oral Non-Peptide Small Molecule GLP-1 Receptor Agonist GSBR-1290

GSBR-1290 achieved a clinically meaningful and statistically significant placebo-adjusted mean weight loss of 6.2% (p<0.0001) in the Phase 2a obesity study and up to 6.9% (p<0.0001) in the capsule to tablet PK study, in both cases at 12 weeks

GSBR-1290 demonstrated generally favorable safety and tolerability results
with low AE-related study discontinuations

Pharmacokinetic data support dose proportional exposure and once-daily oral dosing of GSBR-1290

36-week Phase 2b study in obesity on track to begin in the fourth quarter of 2024

Company to host conference call today at 8:30 a.m. ET

SAN FRANCISCO, June 03, 2024 (GLOBE NEWSWIRE) — Structure Therapeutics Inc. (NASDAQ: GPCR), a clinical-stage global biopharmaceutical company developing novel oral small molecule therapeutics for metabolic and cardiopulmonary diseases, today announced positive 12-week topline obesity data from its Phase 2a study of GSBR-1290, along with positive topline results from its capsule to tablet PK study. Both studies achieved their primary and secondary objectives.

Topline Results Summary

• In the Phase 2a obesity study, GSBR-1290 demonstrated a clinically meaningful and statistically significant placebo-adjusted mean decrease in weight of 6.2%¹ (p<0.0001) at 12 weeks. At Week 12, 67% of GSBR-1290 treated participants achieved ≥6% weight loss and 33% achieved ≥ 10% weight loss, compared to 0% for placebo.
• A capsule to tablet PK study designed to explore a new tablet formulation of GSBR-1290 demonstrated a placebo-adjusted mean weight loss of up to 6.9%¹ (p<0.0001) with the tablet formulation at 12 weeks. In addition, the tablet formulation demonstrated comparable exposure to the prior capsule formulation and pharmacokinetic data support dose proportional exposure and a once-daily dose profile of GSBR-1290.
• GSBR-1290 demonstrated generally favorable safety and tolerability results following repeated, daily dosing up to 120mg. As expected for the GLP1-RA drug class, leading adverse events (AEs) were gastrointestinal (GI)-related and the two most common AEs were nausea and vomiting. GI-related adverse events were generally observed early in treatment and attenuated after titration was completed. AE-related study discontinuations ranged from 5% in the Phase 2a obesity study to 11% in the capsule to tablet PK study. There were zero cases of drug-induced liver injury or persistent liver enzyme elevations reported across the two studies.

“These topline results demonstrate the substantial weight loss effect of GSBR-1290 and its potential to become a best-in-class oral small molecule GLP-1RA as well as an ideal backbone for future combination therapeutics for the treatment of obesity and related diseases,” said Raymond Stevens, Ph.D., Founder and CEO of Structure. “We designed GSBR-1290 to be dosed once-a-day, and are pleased to see the competitive treatment effect at 12 weeks, dose proportional exposure and target engagement over 24 hours.”

Dr. Stevens continued: “We are pleased that our new tablet performed well and that a start low and go-slow titration strategy proved beneficial and we will carry these observations into our planned Phase 2b study. As previously reported, we believe our large safety window will allow us the option to explore higher doses in future studies. As a non-peptide small molecule, our large-scale manufacturing process is expected to be more than capable of meeting the anticipated global demand of a product with the profile of GSBR-1290. We are excited to move into a Phase 2b study in overweight and obese individuals. ”

“By 2030, the global prevalence of obesity is expected to reach 1 billion. There is a need for oral treatments, including small molecules, which are easier to make at scale, more stable thus easier to transport and store, and more cost-effective,” said Ania Jastreboff, M.D., Ph.D., Associate Professor of Medicine and Pediatrics at Yale School of Medicine; Director, Yale Obesity Research Center (Y-Weight), and co-Director of the Yale Center for Weight Management. “All these factors may enable greater treatment reach for this worldwide disease. The phase 2 data with GSBR-1290 demonstrate safety to date and clinically meaningful weight reduction with 12 weeks of treatment and are encouraging for its development as a potential future therapeutic for obesity.”

GSBR-1290 Phase 2b Obesity Study Expected to Begin in Fourth Quarter 2024
Structure plans to submit an IND to the FDA in the third quarter of 2024 to support initiation of trials in chronic weight management and thereafter initiate a Phase 2b obesity study of GSBR-1290 in the fourth quarter of 2024. The 36-week global study is expected to use the tablet formulation of GSBR-1290 and include approximately 300 participants to be treated with multiple doses and dose titration regimens.

About the Phase 2a Study of GSBR-1290 in Obesity
The double-blind, 12-week placebo-controlled Phase 2a clinical trial enrolled 64 healthy overweight or obese participants that were randomized to GSBR-1290 120mg (n=37) or placebo (n=27), dosed once daily with weekly dose titrations.

About the GSBR-1290 capsule to tablet PK study
The 12-week placebo-controlled capsule to tablet PK study (n=54) was designed to evaluate the tolerability, safety and pharmacokinetics of a new tablet formulation of GSBR-1290 and assess three different dosing and titration regimens, while exploring changes in weight during the 12-week duration. Based on the results with the new tablet formulation, Structure anticipates using the tablet formulation for future studies starting with the planned 36-week Phase 2b obesity study.

Conference Call and Webcast Information
Structure will host a conference call and webcast today, June 3, 2024 at 8:30 a.m. Eastern Time. A live webcast of the call will be available on the Investor Relations page of Structure’s website at https://ir.structuretx.com/events-presentations/events. To access the call by phone, participants should visit this link (registration link) to receive dial-in details. The webcast will be made available for replay on the company’s website beginning approximately two hours after the live event. The replay of the webcast will be available for 90 days.

About GSBR-1290 and Structure’s Oral Metabolic Franchise
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 mellitus (T2DM) and obesity. Through the Company’s structure-based drug discovery platform, GSBR-1290 was designed to be a biased GPCR agonist, which selectively activates the G-protein signaling pathway. Structure has completed a Phase 2a study of GSBR-1290 in participants with obesity or who are overweight and T2DM with high body mass index (BMI) ≥27. A Phase 2b study in obesity is expected to start in the fourth quarter of 2024, and the Phase 2 development plan in T2DM is expected to be determined in the second half of 2024. Beyond GSBR-1290, Structure is developing next generation combination GLP-1R candidates together with GIP, amylin, 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 and cardiopulmonary 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 small molecule compounds designed to surpass the manufacturing scalability limitations of traditional biologic and peptide therapies and be accessible to more patients around the world. For additional information, please visit www.structuretx.com.

Source: Structure Therapeutics

Original link: https://ir.structuretx.com/news-releases/news-release-details/structure-therapeutics-reports-positive-topline-data-its-phase