Endevica Bio reports co-agonism of the melanocortin-3 and -4 receptors drives robust weight loss

Endevica Bio has announced that the co-agonism of the melanocortin-3 and melanocortin-4 receptors (MC3/4R) drives robust weight loss, unlocking the melanocortin system as a differentiated mechanism of action to complement and rival current obesity treatments. The company stated that this finding could redefine the therapeutic landscape for general obesity treatment.

For decades, MC4R has been recognised as a key target for obesity. Despite its promise, MC4R-selective approaches have failed to deliver meaningful weight loss in individuals with general obesity, the company stated. Endevica Bio believe they have demonstrated that dual activation of MC3R and MC4R may be the key to unlocking superior weight loss efficacy compared to MC4R agonism alone.

710GO is an orally bioavailable peptide agonist with potent activity on the MC3/4R. It demonstrates preclinical weight loss efficacy in obese nonhuman primates without producing any adverse gastrointestinal effects. Notably, minimal rebound weight gain is observed after cessation of treatment with 710GO.

Endevica Bio's orally available, dual-MC3/4R agonist 710GO demonstrates the following in obese non-human primates:

• 11.7% reduction in body weight over 15 weeks as a monotherapy

• Minimal weight rebound of 1.1% at 7 weeks following cessation of treatment

• No gastrointestinal side effects, including diarrhea or vomiting

• Greater proportion of fat mass loss relative to lean mass loss, compared to GLP-1s

According to the company, beyond functioning as a standalone treatment, MC3/4R co-agonism offers a powerful synergistic mechanism to existing drug classes, including GLP-1 receptor agonists and amylin analogues. Data show that combining Endevica Bio's 710GO with incretins unlocks additive effects, further enhancing weight loss while potentially mitigating incretin-associated side effects.

"Our findings fundamentally change how we think about melanocortin biology in obesity," said Russell Potterfield, CEO of Endevica Bio. "For the first time, we have clear evidence that MC3R plays a pivotal and previously underappreciated role in regulating body weight in nonhuman primates. By harnessing the power of MC3/4R co-agonism, we're charting a new course in obesity treatment, one that goes beyond the limitations of MC4R-targeted therapies and GLP-1s."