Aleniglipron

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 Dec. 08, 2025 - 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.” 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: 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 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. 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. 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 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. 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. 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. 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. _________________________ 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. The content above comes from the network. if any infringement, please contact us to modify.

Listen to the article 4 min This audio is auto-generated. Please let us know if you have feedback. Today, a brief rundown of news from Dyne Therapeutics and Kymera Therapeutics, as well as updates from Wave Life Sciences and Structure Therapeutics that you may have missed.Dyne Therapeutics will seek approval of a new type of exon skipping drug for Duchenne muscular dystrophy. According to Dyne, treatment with the therapy, z-rostudirsen, led to a more than 5% increase in levels of a muscle-protecting protein in a registrational trial. Drug recipients also displayed improvements, after six months, on multiple indicators of motor function, though the study wasnt powered to detect a statistical benefit on those measures. Dyne intends to file for an accelerated U.S. clearance next year in Duchenne patients who have mutations in exon 51 of the dystrophin gene. There is some consternation from investors, as volatility at the Food and Drug Administration and the failures of multiple confirmatory trials have raised concerns about the regulatory bar for Duchenne medicines, wrote Stifel analyst Paul Matteis. Still, Dynes data on functional measures are the best ever generated for a drug of its kind in a placebo-controlled trial, he claimed.Shares of Kymera Therapeutics rose by more than 50% on new study results the company revealed for a protein-degrading drug its developing for inflammatory conditions. Kymeradisclosed in June that the drug, KT-621, appeared safe and able to degrade a tough-to-reach protein in the blood and skin thats linked to inflammation. Data announced on Monday build on those results, indicating KT-621 an oral medication is impacting markers of disease in atopic dermatitis with biologic-like or better efficacy, wrote Mizuho Securities analyst Joseph Catanzaro. One mid-stage trial is ongoing in atopic dermatitis, and a second in asthma should begin next year.Wave Life Sciencessaw its share price nearly double after initial study data suggested one of its drug prospects might have potential treating obesity. When compared to a placebo, a single, low dose of the therapy, an oligonucleotide-based treatment called WVE-007, was associated with a 9% reduction in harmful visceral fat, a 4% decline in total body fat, and a slight improvement in lean mass after three months. There have been no study discontinuations or serious treatment-emergent adverse events, either. Wave is planning Phase 2 trials testing WVE-007 as a monotherapy and alongside incretin drugs for weight loss. The results so far signal this program will be competitive, Leerink Partners analyst Joseph Schwartz wrote.Structure Therapeutics also reported positive results for a prospective obesity drug. Called aleniglipron, the treatment is a GLP-1 pill, much like a therapy known as orforglipronthat Eli Lilly could soon bring to market. In a Phase 2 trial, a 120 milligram dose of aleniglipronspurred weight loss of 11% after nine months compared to a placebo, similar efficacy to Lillys drug, wrote Leerinks David Risinger. And though the drug appeared less tolerable rates of vomiting were higher than whats been observed in testing of orforglipron a low starting dose compared more favorably, Risinger added. Structure said the findings support advancement into Phase 3 trials. Company shares, which debuted at $15 apiece in 2023, nearly doubled and were changing hands Monday morning at over $65 apiece. '