763-P: Glycemic Control, Weight Reduction, and Safety with CT-388, a Signal-Biased Dual GLP-1/GIP Receptor Agonist—Results from a 12-Week Cohort in Adults with Obesity and Type 2 Diabetes

Introduction and Objective: In a phase 1 study (NCT04838405), CT-388 demonstrated a placebo (pbo)-adjusted (adj) weight loss (WL) of 18.8% after 24 weeks in adults with obesity without T2D. Here, we present safety, tolerability, and pharmacodynamic results from an additional cohort of adults with obesity and T2D. Methods: Adults with obesity and T2D (n=19) treated with diet/exercise alone or with metformin, and HbA1c 7.0%−10.0% at baseline (BL) were randomized (4:1) to either once-weekly subcutaneous CT-388 22 mg or pbo over 12 weeks. Key endpoints included change from BL in HbA1c, % WL, and adverse events (AEs). Descriptive statistics and linear mixed-effect models for repeated measures were employed. Results: Among 14 patients (pts) taking CT-388 and 5 taking pbo, BL mean (SD) age was 47 (9) vs 42 (14) years; HbA1c, 8.7% (1.1) vs 9.4% (0.6); and body weight, 95 (14) vs 96 (11) kg, respectively. At 12 weeks, CT-388 and pbo treatment led to a reduction in HbA1c of 3.0% and 0.2%, respectively (pbo-adj least squares mean [LSM] of 2.8% [95% CI: 2.1-3.6%]). Among CT-388-treated pts, 100% (n=14/14) and 50% (n=7/14) achieved HbA1c thresholds of ≤6.5% and <5.7%, respectively. CT-388 and pbo treatment led to a % WL of 8.6% and 1.2% at 12 weeks, respectively (pbo-adj LSM of 7.4% [95% CI 4.9-9.8%]). Among pts taking CT-388, 100% (n=14/14) achieved WL of ≥5%. There were no serious AEs, or AEs leading to discontinuation. GI AEs were the most frequent, with the majority being mild and transient. No clinically notable changes in laboratory or vital signs were noted. Conclusion: In a T2D cohort with obesity, CT-388 led to clinically meaningful improvements in glycemic control, including normalizing dysglycemia, and WL over 12 weeks. Safety/tolerability were in line with incretin-based therapies in similar stages of development. A phase 2 study of CT-388 in pts with T2D has been initiated (NCT06628362). Disclosure A. Steinberg: Employee; Genentech, Inc. Stock/Shareholder; Viking Therapeutics, Pfizer Inc. Employee; Roche Pharmaceuticals, Axcella Health Inc, Carmot Therapeutics, Inc. F.A. Argüelles-Tello: None. L.L. Sánchez-Sánchez: None. W.G. Ortiz: None. M.A. Elliott: Employee; Carmot Therapeutics, Inc. J. Wu: Employee; Roche Pharmaceuticals, Carmot Therapeutics, Inc. J. Zhu: Employee; Genentech, Inc. E. Shearer-Kang: Employee; Genentech, Inc. L. Acosta: None. J.R. Willis: Employee; Genentech, Inc. M. Chakravarthy: Employee; Carmot Therapeutics, Inc, Roche Pharmaceuticals, Genentech, Inc.