Muscle and fat are the body’s only organs that are dynamically regulated in size—growth and reduction in size are affected by the combination of nutrient intake, exercise, growth factors, and activin signaling.
Versanis is the first to tackle obesity by targeting activin type II receptors (ActRII), the activin receptors found in both fat and muscle cells. Signaling through ActRII receptors causes wasting in muscles and storage of fat in adipose tissue. Human genetic studies have implicated members of the activin pathway in obesity.
Mechanism of action in obesity
ActRII biology in adipose tissue
- Activin signaling via ActRII receptors directly promotes lipid storage, acting as a key driver of visceral fat accumulation and obesity.
- Bimagrumab is a potent first-in-class monoclonal antibody that blocks ActRII signaling in adipose cells, mobilizing and metabolizing fat.
ActRII biology in muscle tissue
- Signaling via ActRII receptors inhibits muscle growth and promotes atrophy.
- Blocking activin signaling in skeletal muscles inhibits this atrophy and can promote increases in muscle mass, helping patients with obesity improve body composition and metabolism while losing fat.
Mechanism of action in heart failure
In cardiac muscle, activin signaling has a direct mechanism in promoting contractile protein degradation. Activin signaling is elevated in patients with heart failure and is correlated with disease severity.
ActRII biology in cardiac tissue
- Activin signaling in cardiac tissue promotes degradation of cardiomyocyte proteins leading to degradation of contractile tissue.
- Bimagrumab blocks activin signaling, restoring calcium flux to the sarcoplasmic reticulum and preventing degradation of contractile proteins.
Bimagrumab is a novel and differentiated approach to targeting obesity and heart failure through inhibition of the activin type II receptors that are found in adipose, skeletal muscle, and cardiac muscle cells.
Bimagrumab has been investigated across 21 clinical trials including more than 1,000 patients with exposure to bimagrumab for up to 18 months:
In a phase II study in patients with type II diabetes and obesity, bimagrumab significantly reduced body weight, total body fat, visceral adiposity, and HbA1c while increasing lean mass.
In a phase I/II, bimagrumab improved body composition and insulin sensitivity in insulin-resistant individuals.
In a phase I study, a single dose of bimagrumab decreased adiposity in older adults and also rapidly increased thigh muscle volume and lean body mass.