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PTC-2105 monotherapy (SC injection, 25 mg/kg, 3X/week) treatment of 75-week-old naturally aged DIO-fed mice for 35 weeks led to a 33% loss of fat accompanied by a 7.1% gain of lean mass, for an overall weight loss of 25.9% Treatment with PTC-2105 (SC injection 25 mg/kg, 3X/week) in combination with the GLP-1, semaglutide (SMG), (SC injections, PTC-2105 50 mg/kg, 1X/week + SMG 3X/week, 0.2 mg/kg, increased dose to 0.4 mg/kg after week 5) in 75-week-old naturally aged DIO-fed mice for 35 weeks led to a 66% loss of fat accompanied by a 7.4% gain of lean mass, for an overall weight loss of 58.6% These results are best-in-class with respect to both overall weight loss and the quality of the resulting body composition as measured by DEXA scans in PTC-2105-treated animals compared to reported results for GLP-1s Patients on Retatrutide have a reported 32% total weight loss, comprised of a 22% loss of fat and a 10% loss of muscle at 48 weeks (Ph2, 12 mg once weekly)