Structure Therapeutics (GPCR) Study Update summary

Candidate selection and platform overview

• ACCG-2671 (also referred to as ACCT-2671), an oral small molecule amylin receptor agonist, was selected as the lead candidate for obesity and metabolic disorders.

• Structure-based drug discovery platform, integrating cryo-EM, computational data science, and AI, enabled rapid identification and optimization of 2671.

• 2671 is a dual amylin and calcitonin receptor agonist (DACRA) with competitive efficacy, favorable safety, and once-daily oral dosing.

• Preclinical data show 2671 matches cagrilintide-like efficacy, robust weight loss, and combinability with semaglutide.

• GMP manufacturing and IND-enabling studies initiated to support GLP-tox and early clinical development, with Phase 1 trials planned by end of 2025.

Preclinical efficacy and safety data

• 2671 demonstrated nanomolar binding affinity and subnanomolar activity on amylin and calcitonin receptors in vitro.

• In diet-induced obesity rat models, 2671 produced dose-dependent, cagrilintide-like weight loss and reduced food intake by over 85%.

• Preclinical safety profile includes tolerability up to 300 mg/kg in rats, minimal hERG channel effect, and negative GSH, indicating low liver toxicity risk.

• PK supports once-daily dosing at ≤100 mg/day in humans and chronic disease treatment.

• No significant drug-drug interaction issues identified in preclinical studies.

Clinical development strategy and future plans

• Phase 1 SAD and MAD studies for 2671 expected to start by end of 2025, with data anticipated by end of 2026.

• Phase 2 trials will explore 2671 as both monotherapy and in combination with GLP-1 and potentially other incretins.

• 2671 is positioned as a backbone for potential fixed-dose oral combinations targeting broader metabolic indications.

• Multiple amylin candidates, including DACRAs and SERAs, are being advanced in parallel to optimize therapeutic options.

• Multiple catalysts expected in 2025–2026, including Phase 1 and 2 data readouts and potential expansion into additional indications.