Combination with NLRP3 inhibitor achieves 50% greater weight loss and lean muscle preservation in mice than with semaglutide alone.

As featured in Longevity.Technology

“Inflammation-targeting biotech Halia Therapeutics has reported promising preclinical results from a study combining its investigational compound HT-6184 with semaglutide, the GLP-1 agonist behind weight management drugs like Ozempic and Wegovy. The runaway success of semaglutide has led several biotech companies to explore the potential of combining their therapeutics with the drug to achieve greater weight loss effects and help mitigate any potential impact on muscle mass and function.

Halia’s study, conducted on mice with diet-induced obesity, demonstrated that the combination of HT-6184 with semaglutide enhanced weight loss while preserving lean muscle mass. One of the challenges is obesity management is that muscle tissue, essential for maintaining a higher metabolic rate, can be compromised in the weight loss process.

In the study, mice receiving the combination of HT-6184 and a subtherapeutic dose of semaglutide showed a 50% greater weight loss than those treated with semaglutide alone. With a higher dose of semaglutide, the weight loss was 25% greater than semaglutide on its own. The combination therapy also demonstrated a 10% improvement in lean mass preservation compared with the semaglutide-only group. One of the common challenges with semaglutide treatment is the tendency to hit a weight loss plateau, something Halia claims the combination with HT-6184 appears to overcome in this preclinical model.

HT-6184 is an inhibitor of the NLRP3 inflammasome, a protein complex involved in chronic inflammation, which is linked to various diseases, including obesity-related metabolic dysfunction. Halia’s approach to targeting NEK7, a protein involved in the regulation of NLRP3 activity, is designed to disrupt the inflammasome’s formation and encourage its disassembly, thus reducing inflammation. This anti-inflammatory mechanism is seen as a key factor in the compound’s potential to improve metabolic outcomes in obesity and related conditions, such as Type 2 diabetes, where inflammation plays a role in insulin resistance and metabolic disturbances.

Halia plans to advance HT-6184 into Phase 2 clinical trials later this year, testing the drug in combination with semaglutide for its safety, tolerability, and efficacy in adults with obesity or weight-related comorbid conditions.

“These preclinical findings are truly exciting, showcasing HT-6184’s potential as a game-changing therapy for obesity,” said Halia CEO Dr David Bearss. “Combining HT-6184 with semaglutide enhances weight loss and preserves lean muscle mass—a crucial factor for overall metabolic health. These results bring us closer to a treatment that addresses the complex biology of obesity more holistically.”

When we spoke with Bearss earlier this year, he told this that the company had been watching “the explosion in GLP-1 agonists and how that impacts all kinds of things… It’s interesting how one thing being wrong can have this this wide-ranging systemic effect, so we’re excited to try and pull out all that information and then try to connect the dots.”

The data from this study will be presented at the upcoming Discovery on Target Conference, where the company will discuss HT-6184’s mechanism of action and the broader market potential for the combination therapy.”