Ascletis' ASC47: A Promising Weight Loss Combination with Semaglutide

Ascletis Pharma Inc. (HKEX:1672) has announced promising results from a preclinical study, demonstrating that its muscle-preserving weight loss drug candidate, ASC47, in combination with semaglutide, showed superior weight loss compared to semaglutide monotherapy. This combination therapy has the potential to revolutionize the treatment of obesity, offering a more effective and muscle-preserving solution.

ASC47, a first-in-class drug candidate, has shown remarkable results in preclinical studies. It was designed with unique properties to enable targeted delivery to adipose tissue, resulting in high drug concentrations in a dose-dependent fashion. In diet-induced obese (DIO) mice, ASC47 demonstrated a 7-fold higher drug concentration in the adipose tissue 14 days after the last dose compared to human efficacious drug concentration predicted by a preclinical model. This targeted delivery allows ASC47 to effectively reduce fat mass (-63.5%) compared to semaglutide (-39.6%) in a head-to-head pre-clinical study using a DIO mouse model. Additionally, ASC47 increased total muscle mass (+5.8%) while semaglutide decreased it (-9.3%), indicating muscle-preserving weight loss.



ASC47's unique mechanism of action involves uncoupling protein 1 (UCP-1)-mediated thermogenesis in adipose tissue, which differs from semaglutide's primary action. UCP-1 is a protein found in mitochondria that dissipates energy as heat, promoting fat loss. ASC47 targets and activates UCP-1, leading to increased energy expenditure and fat reduction. In contrast, semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, works by reducing appetite and promoting satiety, leading to decreased caloric intake and weight loss. While both drugs aim to reduce body weight, ASC47's UCP-1-mediated thermogenesis offers an additional pathway for fat loss, potentially explaining its superior weight loss results in preclinical studies compared to semaglutide monotherapy.

In a head-to-head preclinical study using a DIO mouse model, ASC47 in combination with semaglutide demonstrated superior weight loss and muscle preservation compared to tirzepatide. ASC47 reduced total fat mass by -68.0% and increased total muscle mass by +8.1%, while tirzepatide reduced total fat mass by -50.4% and decreased total muscle mass by -3.8%. Total body weight reduction was similar between the two combinations, but ASC47-treated DIO mice showed significantly less caloric intake reduction than tirzepatide-treated DIO mice. These findings suggest that the combination of ASC47 and semaglutide may offer a more effective and muscle-preserving weight loss solution compared to tirzepatide.

The potential synergistic effects of combining ASC47 and semaglutide could lead to more effective weight loss in clinical settings. ASC47's unique properties, such as its extended half-life and favorable safety profile, make it an attractive candidate for combination therapy. Further clinical studies are needed to validate these findings and assess the potential benefits of ASC47 and semaglutide combination therapy in humans.

In conclusion, Ascletis' ASC47, in combination with semaglutide, has shown promising results in preclinical studies, demonstrating superior weight loss and muscle preservation compared to semaglutide monotherapy and tirzepatide. As Ascletis continues to develop ASC47, investors should monitor the progress of its clinical trials and the emerging data on its safety and efficacy. The potential of this combination therapy to revolutionize the treatment of obesity makes it an attractive investment opportunity in the healthcare sector.