851-P: A Phase 1, Double-Blind, Placebo-Controlled Single- and Multiple-Ascending Dose Study of the Novel Lipidated IL-22 Receptor Agonist CK-0045 in Adults with and without Obesity

Introduction and Objective: CK-0045 is a novel long-acting IL-22 receptor agonist with great potential for treatment of patients with metabolic diseases based on preclinical data. Here we present the results of a randomized, double-blind, placebo-controlled, Phase 1 study investigating safety, tolerability, and pharmacokinetics of CK-0045 in healthy participants with and without obesity. Methods: A total of 40 healthy participants were randomized 3:1 to a single subcutaneous dose of 1 - 30 µg/kg CK-0045 or placebo in 5 cohorts in the single ascending dose (SAD) part. In the multiple ascending dose (MAD) part, a total of 36 otherwise healthy participants with obesity (BMI 30 - 39.9) received once-weekly subcutaneous doses of CK-0045 (1.25, 2.5 or 5 µg/kg) or placebo (3:1 ratio) for 6 weeks. Results: CK-0045 was safe at all doses tested, and well-tolerated up to 10 µg/kg in the SAD and 2.5 µg/kg in the MAD. All adverse events were mild or moderate, with dry skin, dry lips, and pruritus being the most frequently reported adverse drug reactions. There were no clinically significant adverse trends in labs, electrocardiograms, or vital signs. CK-0045 treatment resulted in dose-proportional increases in exposure and in target engagement biomarkers. Body weight reductions at week 6 were not dose-dependent but did demonstrate an exposure-dependent relationship when analyzed by CK-0045 exposure tertile (+0.8%, -1.1%, and -1.6%). The weight loss in the highest exposure tertile at week 6 was significantly greater (p=0.04) than in the placebo group (-0.3%). Significant reductions in cholesterol levels were also observed as well as non-significant signals of efficacy on several other metabolic parameters. Conclusion: This Phase 1 study of the novel lipidated IL-22 agonist CK-0045 identified safe and tolerable doses with promising exploratory efficacy trends despite high baseline variability and short treatment duration. Disclosure M. van de Bunt: Employee; Cytoki Pharma. C. Friis: Employee; Cytoki Pharma. F. Cauwberghs: None. R. Jorgensen: Employee; Cytoki Pharma. A. Kjølbye: Employee; Cytoki Pharma.