ORM-5029

ORM-5029 is a first-in-class antibody-drug conjugate (ADC) developed to selectively deliver a catalytic GSPT1 protein degrader to HER2-expressing tumor cells. The drug consists of SMol006, a highly potent GSPT1 degrader, conjugated to pertuzumab, an established HER2-targeting monoclonal antibody. ORM-5029 leverages Orum Therapeutics' Dual-Precision Targeted Protein Degradation (TPD²) platform, which combines the specificity of antibody targeting with the catalytic mechanism of targeted protein degradation. Upon binding to HER2 on tumor cells via its pertuzumab component, ORM-5029 is internalized and releases the GSPT1 degrader payload inside the cell, leading to selective degradation of GSPT1 and subsequent cancer cell death. Preclinical studies have shown robust efficacy in multiple HER2-expressing models—including those resistant to other anti-HER2 therapies—and it is currently being evaluated in Phase 1 clinical trials for advanced solid tumors expressing HER2[1][3][5][8].