Noticias y eventos de Structure Therapeutics Inc (GPCR)GPCRStructure Therapeutics Inc

Structure Therapeutics Reports Clinical Trial Results for ACCG-2671 and Aleniglipron

Structure Therapeutics reported clinical trial results from its two lead product candidates: ACCG-2671, an oral, non-peptide, small molecule dual amylin and calcitonin receptor agonist, and aleniglipron, an oral, non-peptide, small molecule glucagon-like peptide-1 receptor agonist. Structure announced topline data for ACCG-2671 in a Phase 1/2a single ascending dose trial in healthy participants without obesity. In the SAD trial, ACCG-2671 demonstrated a long half-life of approximately 6 days supporting potential once-weekly dosing, with no serious adverse events or events of liver enzyme elevations. Exploratory findings showed pharmacodynamic activity and evidence of target engagement, including a 3.3% mean reduction in body weight following a single dose, as well as an encouraging decrease in CTX-1, a biomarker of bone resorption relevant to bone health. Based on these encouraging findings, the Company has initiated the multiple ascending dose portion of the Phase 1/2a clinical trial with topline data expected in the first half of 2027. Structure also reported 72-week results for aleniglipron in the ACCESS open-label extension clinical trial. Participants receiving the 180 mg dose of aleniglipron achieved up to 16.2% body weight loss at 72 weeks, with no evidence of a plateau in weight loss. Compared with ACCESS participants who previously initiated dosing with a 5 mg starting dose, placebo participants who crossed over to aleniglipron in the OLE started with a lower 2.5 mg dose and demonstrated improved tolerability. Across all dose groups, fewer than 5% of participants discontinued treatment due to adverse events, and no off-target safety signals were observed. These results reinforce aleniglipron's previously observed clinical profile, with consistent, potentially best-in-class weight loss and favorable tolerability, further supporting the ongoing Phase 3 ACCOMPLISH program which initiated in August. The SAD portion of the Phase 1/2a clinical trial evaluated the safety, tolerability, pharmacokinetics and exploratory PD effects of ACCG-2671 in 31 healthy adult participants without obesity. A wide range of doses were explored in this first-in-human study to inform the appropriate starting dose and titration regimen for the MAD study. Participants received a single dose of 1, 2, 5, or 10 mg of ACCG-2671 or placebo. ACCG-2671 demonstrated a favorable plasma PK profile showing rapid absorption with Tmax at 1 - 1.5 hours. Exposure was consistent with dose proportionality, and the terminal half-life was approximately 6 days supporting further evaluation of daily and weekly dosing. ACCG-2671 was generally well tolerated with a favorable safety profile. There were no SAEs, no drug related treatment-emergent adverse events leading to treatment discontinuation, and no events of drug-induced liver injury. No nausea or vomiting was reported in the placebo, 1 mg or 2 mg dose cohorts. Dose-related gastrointestinal events emerged at 5mg, with nausea and vomiting, and at 10 mg. These findings informed the starting doses and gradual titration strategies currently being evaluated in the ongoing MAD clinical trial. Exploratory findings with a single dose of ACCG-2671 indicated encouraging and early PD activity. A single 10 mg dose was associated with mean body weight reductions of 3.3% at Day 24. CTX-1, a well-recognized biomarker of bone resorption, decreased by approximately 60% on Day 2 across the active dose cohorts. Together, these findings provide evidence of target engagement and support further evaluation of ACCG-2671 as a potential monotherapy as well as part of combination regimens. Structure has begun dosing in the MAD portion of the ongoing Phase 1/2a study of ACCG-2671. The randomized, placebo-controlled MAD portion will evaluate the safety, tolerability and PK of multiple ascending oral doses of ACCG-2671 administered for 84 days across five cohorts of participants living with obesity. The clinical trial will evaluate different doses and titration regimens, dosing frequencies, with daily and weekly dosing regimens, and includes a cohort of participants receiving a stable dose of an injectable GLP-1 receptor agonist, providing an initial assessment of ACCG-2671 when administered in combination with a GLP-1 receptor agonist. The encouraging SAD results observed to date, together with the data from the ongoing MAD clinical trial, could further establish ACCG-2671's potential as a differentiated and valuable treatment option, both as monotherapy and combination therapy with GLP-1 receptor agonists. Topline data for the MAD portion of the Phase 1/2a clinical trial are expected in the first half of 2027. The ACCESS OLE clinical trial is a prespecified 36-week extension of the Phase 2b ACCESS clinical trial (NCT06693843) designed to evaluate the longer-term safety and tolerability of aleniglipron and the durability of weight loss through 72 weeks of treatment. 87% of eligible participants who completed the initial 36-week double-blind treatment period in ACCESS entered the OLE. Participants continued once-daily treatment in the OLE trial, with doses titrated every four weeks, while participants originally assigned to placebo crossed over to aleniglipron at Week 36 starting with a lower 2.5 mg dose. The OLE also evaluated whether the lower starting dose improved gastrointestinal tolerability. Since participants were titrated to the highest dose of 180 mg after Week 60, this resulted in relatively limited exposure to the 180 mg dose by Week 72. Most participants enrolled in the OLE portion of the study completed the 72 weeks on treatment. Building on previously reported interim results from the ACCESS OLE at 56 weeks in March 2026, aleniglipron demonstrated continued weight reduction at 72 weeks. Participants originally randomized to the 45 mg, 90 mg and 120 mg arms in the ACCESS trial who continued into the OLE and dosed up to 180 mg, achieved weight loss of 11.6%, 14.4% and 16.2%, respectively, with no evidence of weight loss plateau in the two top doses. More than one-third of participants in the highest dose cohorts, 90 mg and 120 mg, achieved more than 20% body weight reduction, with mean absolute body weight loss of 35.9 and 40.5 pounds, respectively. Participants, who were originally assigned to placebo in the ACCESS clinical trial and crossed over into the OLE at week 36, started with a 2.5 mg dose of aleniglipron, titrated every four weeks and achieved weight loss of 9.0%, or 22.7 pounds, after 36 weeks of treatment. Aleniglipron's safety and tolerability profile remained consistent through 72 weeks. Treatment discontinuations due to TEAEs occurred in fewer than 5% of participants in the OLE. Placebo participants who crossed over into the OLE with a 2.5 mg starting dose and were gradually up-titrated every four weeks to 180 mg demonstrated improved gastrointestinal tolerability compared with the 5 mg starting dose in the double-blind portion of ACCESS. There were no cases of drug-induced liver injury and all observed liver-enzyme elevations resolved without treatment discontinuation consistent with prior aleniglipron clinical trials. The efficacy seen in the 72-week OLE trial, especially given that participants were titrated to the highest 180 mg dose at approximately Week 60 and most dose groups had not yet reached an efficacy plateau, demonstrated aleniglipron's durable, clinically meaningful and competitive weight reduction and a consistent and promising long-term safety and tolerability profile, reinforcing its potential as a differentiated once-daily oral GLP-1 receptor agonist for chronic weight management. Aleniglipron is currently being evaluated in the ongoing Phase 3 ACCOMPLISH program, comprising two randomized, double-blind, placebo-controlled clinical trials. ACCOMPLISH-1 is enrolling up to 3,600 adults living with obesity or overweight with at least one weight-related comorbidity, while ACCOMPLISH-2 is enrolling up to 1,100 adults living with obesity or overweight and type 2 diabetes mellitus. In both trials, participants will receive placebo or one of three aleniglipron maintenance doses, 45 mg, 90 mg or 180 mg, following a 2.5 mg starting dose and dose escalation at four-week intervals. The program is designed to evaluate the long-term efficacy and safety of aleniglipron and support global regulatory marketing applications for chronic weight management. The company expects topline data in the second half of 2028.

Structure Therapeutics Publishes Phase 2b Trial Results for Aleniglipron

Structure Therapeutics announced a publication in Nature Medicine detailing results from the Phase 2b ACCESS clinical trial of aleniglipron for the treatment of people living with obesity and/or overweight with at least one weight related co-morbidity. The Nature Medicine publication, titled, "Oral small molecule GLP-1 receptor agonist aleniglipron in people with overweight or obesity: a randomized, double-blind, placebo-controlled phase 2b trial," can be accessed online. The publication was released concurrent with an oral presentation during the American Diabetes Association's 86th Scientific Sessions by lead author, Julio Rosenstock, MD, Chair of the aleniglipron program Steering Committee and Clinical Professor of Medicine, University of Texas, Southwestern Medical Center. The data highlights the efficacy from three maintenance dose levels in the core Phase 2b ACCESS study, as well as a predefined interim analysis of the open-label extension safety study that demonstrated the durability of weight loss beyond 36 weeks, and improved tolerability from a lower 2.5 mg starting dose. The data from these studies provide support for the study design of the upcoming Phase 3 program which is expected to initiate in the third quarter of 2026. "The data published today provide important new details around the previously reported reductions in body weight in patients dosed with aleniglipron. Interestingly, participants continued to lose weight after a median follow up of 20 weeks in the open label extension phase of the study after finalizing the 36 weeks in the double-blind treatment period, with no apparent weight loss plateau. This is an important distinction for a once-daily oral, non-peptide GLP-1 receptor agonist to potentially become an additional treatment option for patients," stated Dr. Rosenstock, MD, Chair of the Steering Committee. "The study closely monitored the participant experience and additional impacts across key measures of tolerability, including the ability to restart or increase dosing titration after interruption without substantial increase in emesis events, which may be helpful for clinicians to gain a clinical perspective of treatment tolerance."

Structure Therapeutics Appoints Matthew Lang as COO and General Counsel

Structure Therapeutics announced the appointment of Matthew Lang as COO and general counsel. Lang most recently served as chief legal officer and secretary at Metsera.