CB1R Inverse Agonist Biology

CRB-913 is a second-generation highly peripherally restricted CB1 receptor inverse agonist designed to treat obesity and related conditions. The drug has demonstrated markedly enhanced peripheral restriction versus rimonabant, the first-generation CB1 receptor inverse agonist, in both lean and obese mice. CB1 inverse agonism is a clinically validated mechanism to induce weight loss. Clinical data from multiple experimental CB1 inverse agonists demonstrated an increase in metabolism and energy expenditure and a reduction in food intake resulting in weight loss and improvement in related clinical outcomes. We are currently conducting IND enabling studies and expect to commence a Phase 1 clinical study in the first quarter of 2025.

In a DIO mouse model, CRB-913, as a monotherapy and in combination with incretin analogs (tirzepatide, semaglutide, or liraglutide), demonstrated a reduction in body weight in DIO mice and improvements were observed in body fat content, leptinemia, insulin resistance, liver triglycerides, liver fat deposits, and liver histology.