BMS 963272 / BMS - LARVOL DELTA

The inhibitor VB-87531 synergizes with tirzepatide and semaglutide for greater weight loss in DIO mice. (PubMed, Biochem Biophys Res Commun) - "Excessive caloric intake, particularly dietary triglycerides contributes to the development of obesity...The human MOGAT2 inhibitor BMS-963272 has been demonstrated to induce weight loss in healthy obese individuals, thereby positioning hMOGAT2 as a promising target for weight management interventions...When combined with tirzepatide, VB-87531 exhibited dose-dependent modulation of weight loss and food intake. These findings indicate that not only does VB-87531 have potential as a standalone therapy, but that it also holds promise in combination with GLP-1 receptor and GLP-1/GIP dual receptor agonists to achieve further weight loss and appetite suppression."

Journal • Preclinical • Genetic Disorders • Obesity • FGF21 • LEP

MGAT2 inhibitor decreases liver fibrosis and inflammation in murine NASH models and reduces body weight in human adults with obesity. (PubMed, Cell Metab) - P1 | "Consistent with the findings in rodent models, BMS-963272 elevated plasma long-chain dicarboxylic acid, indicating robust pharmacodynamic biomarker modulation; increased gut hormones GLP-1 and PYY; and decreased body weight in human subjects. These data suggest MGAT2 inhibition is a promising therapeutic opportunity for NASH, a disease with high unmet medical needs."

Journal • Preclinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

A Study to Evaluate the Safety, Tolerability, and Drug Levels of BMS-963272 in Participants With Nonalcoholic Fatty Liver Disease (clinicaltrials.gov) - P1b | N=9 | Terminated | Sponsor: Bristol-Myers Squibb | N=60 ➔ 9 | Trial completion date: Dec 2021 ➔ Aug 2021 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2021 ➔ Aug 2021; Business objectives have changed

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hepatology • Non-alcoholic Fatty Liver Disease

Screening Hit to Clinical Candidate: Discovery of BMS-963272, a Potent, Selective MGAT2 Inhibitor for the Treatment of Metabolic Disorders. (PubMed, J Med Chem) - "A novel chemistry route was developed to synthesize aryl dihydropyridinone analogs to explore structure-activity relationship around this hit, leading to the discovery of potent and selective MGAT2 inhibitors 21f, 21s, and 28e that are stable to liver microsomal metabolism. After triaging out 21f due to its inferior in vivo potency, pharmacokinetics, and structure-based liabilities and tetrazole 28e due to its inferior channel liability profile, 21s (BMS-963272) was selected as the clinical candidate following demonstration of on-target weight loss efficacy in the diet-induced obese mouse model and an acceptable safety and tolerability profile in multiple preclinical species."

Clinical • Journal • Metabolic Disorders • Obesity • HMGA2

A Study to Evaluate the Safety, Tolerability, and Drug Levels of BMS-963272 in Participants With Nonalcoholic Fatty Liver Disease (clinicaltrials.gov) - P1b; N=60; Recruiting; Sponsor: Bristol-Myers Squibb; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Hepatology • Non-alcoholic Fatty Liver Disease

A Study to Evaluate the Safety, Tolerability, and Drug Levels of BMS-963272 in Participants With Nonalcoholic Fatty Liver Disease (clinicaltrials.gov) - P1b; N=60; Not yet recruiting; Sponsor: Bristol-Myers Squibb

Clinical • New P1 trial • Hepatology • Non-alcoholic Fatty Liver Disease

A Multiple Dose Study to Assess the Safety and Tolerability of BMS-963272 in Obese But Otherwise Healthy Adults (clinicaltrials.gov) - P1; N=36; Completed; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Completed

Clinical • Trial completion • Metabolic Disorders • Obesity

A Study to Assess the Drug-drug Interaction of BMS-963272 and Rosuvastatin (clinicaltrials.gov) - P1; N=28; Completed; Sponsor: Bristol-Myers Squibb; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Study to Assess the Drug-drug Interaction of BMS-963272 and Rosuvastatin (clinicaltrials.gov) - P1; N=28; Active, not recruiting; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study to Assess the Drug-drug Interaction of BMS-963272 and Rosuvastatin (clinicaltrials.gov) - P1; N=28; Recruiting; Sponsor: Bristol-Myers Squibb; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open