334-OR: Pemvidutide (ALT-801) , a Balanced (1:1) GLP-1/Glucagon Dual Receptor Agonist, Induces Rapid and Marked Weight Loss without the Need for Dose Titration in People with Overweight/Obesity

Background: Weight loss is the cornerstone of therapy for people with overweight/obesity. Pemvidutide is a dual GLP-1/glucagon receptor agonist that provides GLP-1/glucagon agonism in a balanced (1:1) ratio, which is hypothesized to enhance weight loss and minimize gastrointestinal intolerance. Methods: 34 subjects with overweight/obesity (BMI 25.0-40.0 kg/m2) without diabetes were randomized in double-blind manner to pemvidutide (1.2, 1.8 or 2.4 mg) or placebo subcutaneously weekly for 12 weeks without dose titration or lifestyle therapy. Study endpoints included safety/tolerability, weight loss and cardiometabolic outcomes. Results: At 12 weeks, significant weight loss was achieved with 1.8 mg (10.3%) and 2.4 mg (9.0%) of pemvidutide, and significant improvements or trends in cardiometabolic risk factors were observed at all pemvidutide doses (Table 1) . No increases in heart rate, fasting glucose or HbA1c were observed in any group. Mild, transient nausea was the most frequent adverse event (AE) ; no severe/serious AEs or AE-related study discontinuations were reported. Conclusion: Pemvidutide induces robust weight loss and improves cardiometabolic risk factors without dose titration. These data support the development of pemvidutide as a promising treatment for obesity and its comorbidities. Disclosure S.Klein: Advisory Panel; Altimmune, Consultant; Janssen Research & Development, LLC, ProSciento, Research Support; Janssen Research & Development, LLC. S.K.Browne: Employee; Altimmune. J.J.Nestor: Consultant; Altimmune, Employee; EuMederis Pharmaceutials, Inc., Mederis Diabetes, LLC, Spitfire Pharma, Inc. M.Harris: Employee; Altimmune. A.Suyundikov: Employee; Altimmune. R.Casper: Employee; Altimmune. S.M.Steele: Employee; Altimmune. J.D.Payne: None. V.Krishnan: Employee; Altimmune. M.Roberts: Employee; Altimmune. Funding Altimmune, Inc.