CLIO-8221

**CLIO-8221** is a clinical-stage, HER2-targeted dual-payload antibody-drug conjugate developed by Callio Therapeutics for advanced HER2-expressing solid tumors. It uses an Fc-engineered trastuzumab-derived anti-HER2 antibody and a site-specific, protease-cleavable hydrophilic linker to co-deliver the topoisomerase I inhibitor exatecan and the ATR inhibitor berzosertib. Following HER2-mediated tumor-cell binding and internalization, the payloads are intended to induce DNA damage and block ATR-mediated DNA damage-response signaling, respectively, with the goal of overcoming resistance to topoisomerase I inhibitor-based ADCs. CLIO-8221 is being evaluated as intravenous monotherapy in the Phase 1/2 CLIO-8221-001 study in patients with metastatic or unresectable HER2-expressing solid tumors, including patients previously treated with trastuzumab deruxtecan. ([clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07300943))