Ascletis' ASC47 Plus Semaglutide Shows Superior Weight Loss in Preclinical Study
核心洞察
Ascletis (搜索)' ASC47, combined with semaglutide, demonstrated a 56.7% greater reduction in body weight compared to semaglutide alone in diet-induced obese mice.
The combination therapy restored body composition in obese mice to levels comparable with healthy, non-obese mice, preserving muscle mass during weight loss.
ASC47 low dose combinations with semaglutide were well tolerated and significantly reduced liver enzyme levels compared to vehicle treatment in obese mice.
Ascletis (搜索) Pharma Inc. has announced positive preclinical results for its investigational drug ASC47, a first-in-class muscle-preserving weight loss candidate, when used in combination with semaglutide. The study, conducted in diet-induced obese (DIO) mice, demonstrated that a low dose of ASC47 combined with semaglutide led to superior weight loss compared to semaglutide monotherapy.
The combination of ASC47 (3 mg/kg, subcutaneous injection once every four weeks) and semaglutide (30 nmol/kg, subcutaneous injection once daily) resulted in a 36.2% reduction in total body weight, compared to a 23.1% reduction with semaglutide alone. This represents a 56.7% greater reduction in body weight with the combination therapy.
Muscle Preservation and Body Composition
An important aspect of the study was the impact on body composition. The ASC47 low dose combination treatments restored the body composition of obese mice to levels similar to those of healthy, non-obese mice. Specifically, the percentage of total muscle mass over total body weight in the combination groups (68.8%) was comparable to healthy controls (66.0%). Semaglutide monotherapy did not achieve this restoration of healthy body composition.
Liver Enzyme Reduction and Safety Profile
The combination therapy also demonstrated a favorable safety profile. ASC47 low dose combinations were well tolerated in obese mice and led to a statistically significant reduction in levels of liver enzymes, such as alanine aminotransferase (ALT), compared to vehicle treatment in obese mice.
Additional Metabolic Benefits
Furthermore, the study revealed that ASC47, both as a monotherapy and in combination with semaglutide, significantly reduced fasting blood glucose, cholesterol, and LDL-C levels compared to vehicle-treated obese mice. Notably, the combination treatments resulted in superior reductions in fasting blood glucose, cholesterol, and LDL-C compared to semaglutide monotherapy.
Mechanism of Action
Interestingly, cumulative caloric intake was statistically higher in obese mice treated with ASC47 low dose combination treatments compared to those treated with semaglutide alone. This suggests that ASC47 may have a different mechanism of action compared to incretin-based drugs.
Ongoing Clinical Development
ASC47 is an adipose-targeted, once-monthly subcutaneously injected thyroid hormone receptor beta (THRβ (搜索)) selective small molecule agonist. Interim data from an ongoing Phase I single ascending dose (SAD) study in Australia (NCT06427590) in subjects with elevated LDL-C showed that ASC47 demonstrated a good tolerability profile up to 90 mg, with no serious adverse events or discontinuations due to adverse events. The majority of adverse events were mild, with no gastrointestinal or cardiac adverse events reported.
Ascletis (搜索) is currently conducting Phase IIa clinical trials of ASC47 in patients with obesity (搜索) in Australia, with topline data expected in the second quarter of 2025. The company is also developing ASC30, a GLP-1 receptor (搜索) biased small molecule, as both a once-daily oral tablet and a once-monthly subcutaneous injection for the treatment of obesity. Phase Ib clinical trials for both formulations of ASC30 are underway in the U.S., with topline data expected in the first quarter of 2025.
"We are excited by these data showing that adipose-targeted ASC47 low dose combination treatments achieved 56.7% more relative weight loss compared to semaglutide monotherapy. Importantly, in the preclinical study, adipose-targeted ASC47 low dose combination treatments produced healthy weight loss, increasing our confidence that ASC47-based combination therapies may clinically improve weight loss and muscle preservation compared to incretin-based drugs alone," said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis (搜索).