Structure Therapeutics Inc. (NASDAQ: GPCR) has announced the selection of ACCG-2671 as its lead oral small molecule amylin receptor agonist for the treatment of obesity. This Dual Amylin and Calcitonin Receptor Agonist (DACRA) is poised to enter Phase 1 clinical trials by the end of 2025, marking a significant step in the development of oral therapies for weight management.
Preclinical Efficacy and Safety
Preclinical studies have demonstrated that ACCG-2671 exhibits potent target engagement, leading to robust weight loss and a favorable safety profile. These findings support its potential for once-daily oral administration, offering a convenient alternative to injectable treatments. The drug's efficacy in preclinical models mirrors that of cagrilintide, a known amylin analogue, but with the advantage of an oral small molecule formulation.
Mechanism of Action and Therapeutic Potential
ACCG-2671 targets the amylin receptor, a key regulator of glycemia and energy balance. Amylin, a hormone co-secreted with insulin, plays a crucial role in reducing food intake and slowing gastric emptying. By acting as a DACRA, ACCG-2671 not only stimulates the amylin receptor but also engages the calcitonin receptor, potentially enhancing its therapeutic effects on weight management and metabolic control.
Raymond Stevens, Ph.D., Founder and Chief Executive Officer of Structure Therapeutics, stated, "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."
Strategic Positioning and Future Development
Structure Therapeutics envisions ACCG-2671 as a foundational therapy that can be used alone or in combination with other agents, such as their oral GLP-1 molecule GSBR-1290. This dual approach allows for the development of fixed-dose oral combinations, potentially improving patient access and adherence to weight loss medications.
Xichen Lin, Ph.D., Chief Scientific Officer of Structure Therapeutics, added, "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."
The company's structure-based drug discovery platform has enabled the rapid advancement of ACCG-2671, positioning it as the most advanced oral small molecule in the amylin-based drug category. Structure Therapeutics is continuing to develop a series of amylin-based drug candidates to further solidify its leadership in this therapeutic area.
Market Opportunity
The obesity market is currently dominated by injectable GLP-1 receptor agonists. Structure Therapeutics aims to address the limitations of these therapies by developing oral small molecule alternatives that offer improved scalability, combinability, and patient convenience. With both an oral GLP-1 and an oral amylin agonist in development, the company is strategically positioned to capture a significant share of this rapidly growing market.
