765-P: DA-1241, a Novel GPR119 Agonist: Data on Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) from Part 2 of a Phase 1b Multiple Ascending Dose (MAD) Study in Patients with Type 2 Diabetes Mellitus (T2DM)

Background and Aim: DA-1241 is a novel small molecule selective GPR119 agonist. In preclinical studies DA-1241 enhanced metabolic hormones, and improved metabolic control characteristics. The primary objective of Part 2 was to assess safety and tolerability of multiple once daily oral doses of DA-1241 versus placebo and Sitagliptin in T2DM. Secondary objectives were to establish PK and PD characteristics. Methods: Part 2 was a double blind placebo and Sitagliptin (SG) controlled study with three sequential cohorts of T2DM (n=25/cohort) blinded and randomized (3:1:1) to receive DA-1241: 25, 50 or 100 mg (n=15/cohort), placebo (n=5/cohort) or Sitagliptin (n=5/cohort) single daily oral doses for 56 days. Results: 84 subjects were enrolled in Part 2, 3 subjects were withdrawn due to TEAEs (1 active, 2 placebo), 72 subjects completed the study. There were no relevant demographic imbalances (Age 56.8 ± 7.3, BMI 29.4 ± 3.3). Doses tested were generally safe and well tolerated. The most frequent TEAEs were mild GI side effects (nausea, diarrhea, abdominal pain), all resolved spontaneously. Day 56 PK Cmax and AUC0-tau parameters were dose proportional. Fasting plasma glucose trended towards improvement for all DA-1241 doses, as did incremental glucose exposure after MMTTs (Change from Baseline to Day 56 iAUC 0-4h: 25mg: 18.5±89.2, 50mg: -5.1±86.8, 100mg: -38.6±58.7, Placebo: 34.4±145.9, SG: -23.9±132.8) and time spent at BG Conclusion: This phase 1b study in T2DM showed favorable safety, tolerability and PK profiles of DA-1241. Biomarkers and PD data confirmed the mechanism of action and showed favorable efficacy data trends. Disclosure M. Kim: Employee; Self; Dong-A ST Co. Ltd. D. Lee: Employee; Self; Dong-A ST Co. Ltd. J. Jeong: Employee; Self; Dong-A ST Co. Ltd. M. Grimm: None. B. B. Franey: None. M. Hompesch: Other Relationship; Self; Wiley, Stock/Shareholder; Self; ProSciento, Inc.