calotatug ginistinag

**Calotatug ginistinag (XMT-2056)** is a HER2-targeted **immune stimulating antibody conjugate (ISAC)**, also described as an antibody-drug conjugate (ADC), developed using Mersana Therapeutics' proprietary **Immunosynthen platform**. It consists of an anti-HER2 antibody (HT-19) engineered to bind a novel epitope, conjugated via a **XMT-1519 linker-payload (LP, HY-148067)** to a **STING agonist payload**, enabling targeted delivery and activation of the **STING (stimulator of interferon genes) pathway** in tumor cells and tumor-resident immune cells. This induces potent **innate anti-tumor immune responses**, including upregulation of immune pathway genes like PD-L1, antibody-dependent cellular cytotoxicity (ADCC), and tumor regressions at low doses in preclinical models across various **HER2-expression levels** (positive, low, mutant). It demonstrates synergy with HER2-targeted agents (e.g., trastuzumab, pertuzumab) and checkpoint inhibitors, with favorable pharmacokinetics and tolerability in non-human primates. Currently in **Phase 1** trials (NCT05514717) for HER2-expressing advanced solid tumors, with prior clinical hold resolved.[1][2][3][4][5]