在此前的临床前研究中，常规剂量ASC47(45mg/kg，皮下注射，每两周一次)单药显示出总体重下降24.6%的疗效，与司美格鲁肽单药(下降23.1%，30nmol/kg，皮下注射，每日一次)疗效相似。常规剂量ASC47使肌肉总量增加5.8%，而司美格鲁肽使肌肉总量减少9.3%(链接)。On December 18, Gelonghui announced that ASCLETIS-B (01672.HK) has reported that the Board of Directors declared that the first-in-class obesity treatment candidate drug ASC47, used in conjunction with semaglutide, has shown encouraging efficacy in studies on diet-induced obesity (DIO) mouse models.
ASC47 is a thyroid hormone receptor β (THRβ) selective small molecule agonist, developed independently by ASCLETIS, designed for fat targeting and to be administered subcutaneously once a month. ASC47 has unique differentiated characteristics that allow it to target fat, producing dose-dependent high drug concentrations in adipose tissue.
Interim data from a Phase I single ascending dose (SAD) study (NCT06427590) conducted in Australia on subjects with elevated low-density lipoprotein cholesterol (LDL-C) show that the half-life of subcutaneously injected ASC47 is 21 days. Furthermore, ASC47 demonstrated good tolerance, with the current dose increased to 90mg, showing no severe adverse events (SAE), and no treatment discontinuations due to adverse events (AE). Most AEs were mild (Grade 1). No gastrointestinal or cardiac AEs were reported, and there were no reports of liver enzyme abnormalities (link). Higher dose studies are ongoing.
In previous preclinical studies, the standard dose of ASC47 (45mg/kg, subcutaneously, every two weeks) alone showed an overall weight reduction efficacy of 24.6%, which is similar to the efficacy of semaglutide alone (23.1% reduction, 30nmol/kg, subcutaneously, once daily). The standard dose of ASC47 resulted in a 5.8% increase in total muscle mass, while semaglutide led to a 9.3% decrease in total muscle mass (link).
ASC47 is a fat-targeting, subcutaneously administered thyroid hormone receptor β (THRβ) selective small molecule agonist given once a month. Interim data from the Phase I single ascending dose (SAD) study (NCT06427590) in subjects with elevated LDL-C in Australia has been released. ASC47 is currently undergoing clinical trials for obese patients in Australia, with top-line data for the Phase IIa study expected to be released in the second quarter of 2025. In addition to ASC47, ASCLETIS is also developing ASC30, which has entered Phase I clinical trials for obesity treatment. ASC30 is a small molecule GLP-1R that can be taken orally once a day or injected subcutaneously once a month. Both ASC30 oral tablets (NCT06680440) for daily administration and ASC30 subcutaneously injected once a month (NCT06679959) are currently undergoing Phase I clinical trials for obesity treatment in the USA. Top-line data is expected to be released in the first quarter of 2025.
