Structure Therapeutics (GPCR) Study Update summary

Lead Candidate Selection and Platform Overview

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

• Preclinical data show cagrilintide-like efficacy, robust weight loss, and strong safety margins, with nanomolar binding affinity and subnanomolar activity at amylin and calcitonin receptors.

• Structure-based drug discovery platform, leveraging cryo-EM, GPCR dynamics, and machine learning, enabled efficient candidate design and optimization.

• GMP manufacturing and IND-enabling studies have been initiated, with Phase 1 SAD/MAD studies planned to start by end of 2025.

• ACCG-2671 is positioned as a backbone for future fixed-dose oral combinations and broader metabolic disease therapies.

Preclinical Data and Development Plans

• In DIO rat models, ACCG-2671 achieved up to 15% body weight loss, comparable to cagrilintide, and showed efficacy in combination with semaglutide.

• Safety profile includes high tolerability in rats, minimal hERG effect, negative GSH, and preclinical PK supports once-daily dosing at ≤100 mg/day in humans.

• Phase 1 clinical study initiation is expected by year end 2025, with Phase 2 to explore monotherapy and combinations for chronic weight management.

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

• ACCG-2671 is the first disclosed oral small molecule amylin-based development candidate.

Strategic Vision and Pipeline Expansion

• ACCG-2671 and GSBR-1290 (oral GLP-1) form the backbone for future obesity and metabolic disease therapies, with plans for fixed-dose combinations and expansion into diabetes, heart failure, and kidney disease.

• Multiple amylin candidates (DACRA and SERA) to be advanced in parallel to optimize efficacy and safety.

• Strong financial position with $915 million in cash to support ongoing R&D and pipeline growth.

• Focus on accessibility, scalability, and cost advantages of oral small molecules over peptide-based therapies.

• Platform supports a franchise strategy with multiple small molecule candidates for combination therapies in metabolic diseases.