Structure Therapeutics has selected its lead oral small molecule amylin receptor agonist, ACCG-2671, which the company will develop for the treatment of obesity. In preclinical studies, ACCG-2671 demonstrated potent and balanced in vitro activities toward the key amylin receptor and the calcitonin receptor. ACCG-2671 also further demonstrated robust in vivo efficacy and a pharmacokinetic (PK) and safety profile supporting once-daily oral dosing in humans.
Amylin is a hormone that plays an important role in regulating glycaemia and energy balance and is recognised as a promising therapeutic target for obesity and related diseases due to its effects on reducing food intake and slowing the rate of gastric emptying. ACCG-2671 was designed as an oral small molecule Dual Amylin and Calcitonin Receptor Agonist (DACRA) and is expected to enter Phase 1 clinical development by year end 2025.
Amylin is co-secreted with insulin from pancreatic beta cells in response to nutrient ingestion. Amylin has important physiological effects including reducing appetite, increasing satiety, leptin sensitivity and energy expenditure. Preclinical data from current amylin-based treatments in development suggest a potential for amylin to reduce fat mass and preserve lean mass.
Two types of amylin-based treatments for the treatment of obesity are currently being developed: DACRAs that target both the amylin and calcitonin receptors; and selective amylin receptor agonists (SARAs) that preferentially target the amylin receptor.
“We believe amylin-based therapies are an important next-generation component of the treatment landscape for obesity and related conditions due to their potential for significant weight loss, favorable tolerability profile, and lean muscle mass preservation,” said Dr Raymond Stevens, Founder and Chief Executive Officer of Structure Therapeutics. “As an oral small molecule, we envision ACCG-2671 as an additional backbone therapy to improve scalability, combinability and ultimately expand patient access to amylin-based weight loss medicines. We are in a unique position to have a potentially best in class GLP-1 oral small molecule with GSBR-1290 and now the most advanced amylin oral small molecule, both intended for use as monotherapies and as backbones for fixed dose oral combinations.”
ACCG-2671 is the first disclosed oral small molecule amylin-based development candidate, with Phase 1 study initiation expected by year end 2025.
“The preclinical data demonstrate cagrilintide-like efficacy with an oral small molecule profile, underscoring ACCG-2671’s potential as a meaningfully differentiated oral treatment for obesity and related conditions,” said Dr Xichen Lin, Chief Scientific Officer of Structure Therapeutics. “Our proven GPCR structure-based drug discovery platform enabled us to rapidly advance ACCG-2671 as the lead amylin receptor agonist. We are now developing a series of amylin-based drug candidates using our technology platform to maintain our leadership in this exciting space.”
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