HCR-588

HCR-588 is a preclinical-stage antibody-peptide conjugate (APC) being developed by Helicore Biopharma for the treatment of obesity and cardiometabolic diseases. The drug utilizes a triple-mechanism approach built on the HCR-188 backbone, which is a monoclonal antibody designed to bind and deplete circulating gastric inhibitory polypeptide (GIP) ligands. This antibody backbone is conjugated to two distinct peptide payloads: a biased glucagon-like peptide-1 receptor (GLP-1R) agonist and a selective amylin receptor (AMY1R) agonist. The biased GLP-1R agonism is specifically engineered to reduce receptor internalization and desensitization, aiming to maintain therapeutic efficacy while limiting gastrointestinal side effects. The AMY1R component demonstrates high selectivity with minimal activity at the calcitonin gene-related peptide receptor (CGRPR). HCR-588 is designed for quarterly or less frequent subcutaneous dosing, representing a long-acting multi-pathway strategy for weight management and metabolic health.