Summary

Emugrobart, an investigational, anti-latent myostatin, is a SMART-Ig* using recycling and sweeping antibody technologies that eliminates latent myostatin from plasma and tissues.¹ Latent myostatin is an inactive form that is mainly secreted from muscle cells, and is activated by BMP-1 and other protein degrading enzymes. Activated myostatin inhibits muscle growth and hypertrophy.²

Proposed Mechanism of Action

The Activin and SMAD Pathways: Critical Regulators of Muscle Growth

The TGF-B superfamily is a large group of signaling molecules including activins, and growth and differentiation factors (GDFs) like myostatin and GDF11.³ The SMAD pathway plays a crucial role in muscle development, growth, and remodeling.^4,5

Three core ligands, Activin A, Myostatin and GDF11 bind to ActRII receptors and have different effects on muscle biology.⁶ Myostatin and to a lesser extent Activin A, are recognized as a natural brake for muscle growth.⁷ GDF11 has been shown to inhibit muscle regeneration, suggesting a potential role in age-related muscle decline.³

Emugrobart (RO7203942) Is Specific for Latent Myostatin

Targeting latent myostatin (LM) leads to specific depletion of mature myostatin (MM) without affecting GDF11 or Activin A activity.⁸ Specific depletion of myostatin may be associated with increased muscle function in terms of muscle strength and metabolic activity.^1,9 Although preliminary animal and human obesity studies imply that myostatin regulation is altered ^10,11, its role in regulating metabolic processes requires further exploration.¹² Emugrobart, via sustained myostatin signaling blockade, demonstrated muscle growth, muscle function increase and loss of fat mass in rodent models.¹