Peptide News Digest

#Small-Molecule-Glp-1

3 stories

Clinical Trials · View digest

Structure Therapeutics (NASDAQ: GPCR) Anchored the Obesity Runner-Up Narrative With the Phase 2b ACCESS II Trial of Aleniglipron (Once-Daily Oral Small-Molecule GLP-1 Receptor Agonist) That Documented 16.3% Placebo-Adjusted Mean Weight Loss at the 180 mg Dose (39 lbs) and 16.0% Weight Loss at the 240 mg Dose (37 lbs) at 44 Weeks Positioning Aleniglipron as the Highest-Efficacy Oral GLP-1 Agonist Data Reported to Date; The Core Phase 2b ACCESS Study Had Documented 11.3% Weight Loss at 120 mg at 36 Weeks; ACCESS Open-Label Extension (OLE) Study Documented Continued Weight Loss From 36 Weeks Up to 16.2% (40.5 lbs) With 120 mg at 56 Weeks With No Observed Plateau; Tolerability Profile Consistent With the GLP-1 Class With Only 3.7% Adverse-Event-Related Treatment Discontinuation Across All Active Arms at 120 mg or Higher From Weeks 28 to 44; Phase 3 Initiation Expected in H2 2026

Structure Therapeutics (NASDAQ: GPCR) reported detailed Phase 2b ACCESS II trial results for aleniglipron (once-daily oral small-molecule GLP-1 receptor agonist for obesity). Key efficacy: 16.3% placebo-adjusted mean weight loss at the 180 mg dose (39 lbs) and 16.0% weight loss at the 240 mg dose (37 lbs) at 44 weeks. This positions aleniglipron as the highest-efficacy oral GLP-1 agonist data reported to date, above Eli Lilly's orforglipron (Foundayo, 7.5-11.2% at 72 weeks in ATTAIN-1) and Novo Nordisk's Wegovy pill (oral semaglutide 25/50 mg, roughly 15% at 68 weeks in OASIS 4). The core Phase 2b ACCESS study had documented 11.3% placebo-adjusted weight loss at 120 mg at 36 weeks. The ACCESS Open-Label Extension (OLE) study documented continued weight loss from 36 weeks up to 16.2% (40.5 lbs) with 120 mg at 56 weeks with no observed plateau, an important tolerability and durability signal. Tolerability profile is consistent with the GLP-1 receptor agonist class with only 3.7% adverse-event-related treatment discontinuation across all active arms in participants who reached 120 mg or higher from weeks 28 to 44. Phase 3 initiation is expected in H2 2026. Aleniglipron is a non-peptide small molecule that binds the GLP-1 receptor, similar to Lilly's orforglipron but distinct from the peptide-based semaglutide and tirzepatide; the small-molecule format provides manufacturing scalability advantages over peptide APIs.

Clinical Trials · View digest

Ascletis ASC30 Posters at ECO 2026: Once-Monthly Subcutaneous Depot Shows 7.5% Placebo-Adjusted Weight Loss at 16 Weeks

Ascletis announced multiple poster presentations at the 33rd European Congress on Obesity (ECO 2026) opening May 12 in Istanbul. ASC30, a first-in-class small-molecule GLP-1R fully biased agonist developed for once-daily oral and once-monthly to once-quarterly subcutaneous dosing, will be featured across formulation, PK, and clinical-data posters. The Phase 2 13-week study previously reported 7.7% placebo-adjusted weight loss at 60 mg oral dosing; the once-monthly subQ depot formulation achieved 7.5% placebo-adjusted weight loss at 16 weeks after three monthly doses, with topline T2D Phase 2 data expected Q3 2026. The subQ depot angle directly challenges Pfizer's MET-097i monthly thesis with a different mechanism (small-molecule GLP-1R biased agonist vs ultra-long-acting peptide).

Research · View digest

Nature (May 6): Brain Reward Circuit Inhibited by Next-Generation Weight-Loss Drugs — UVA Team Shows Small-Molecule GLP-1s Engage Central Amygdala Glp1r+ Neurons

A Nature paper published May 6 from a University of Virginia team developed humanized GLP1R mouse models to investigate how small-molecule GLP1R agonists — including orforglipron (Foundayo) — regulate feeding behavior. Beyond canonical hypothalamic and hindbrain networks that control metabolic homeostasis, the team showed these oral compounds recruit a discrete population of Glp1r-expressing neurons in the central amygdala and selectively suppress consumption of palatable foods by reducing dopamine release in the nucleus accumbens — a parallel hedonic-feeding circuit distinct from the homeostatic mechanism that drives most GLP-1 weight loss. The work explains why patients on small-molecule oral GLP-1s often report reduced food cravings and pleasure-driven eating, and identifies a neural circuit with implications for substance-use disorder and binge eating beyond obesity.