California- and Taiwan-based Acepodia (TWSE: 6976) has received US FDA clearance to begin Phase I testing of ACE723, a GPC3-targeted dual-payload antibody-drug conjugate (ADC) for unresectable or metastatic hepatocellular carcinoma (HCC). The clearance marks the first clinical-stage program generated from the company’s Antibody-Dual-Drugs Conjugation (AD2C) platform.
HCC accounts for more than 70% of liver cancer cases worldwide. Although the treatment landscape has broadened considerably since sorafenib's approval in 2007 — now encompassing checkpoint inhibitor combinations and multi-kinase inhibitors across first and second lines — no approved therapy is specifically validated after failure of immunotherapy-based first-line regimens, which have become standard of care. That post-IO progression setting represents the most pressing unmet need in the disease.
ACE723 targets glypican-3 (GPC3), a heparan sulfate proteoglycan frequently overexpressed on HCC tumor cells. The molecule uses Acepodia's AD2C platform to conjugate two distinct cytotoxic payloads to an anti-GPC3 antibody, with the goal of delivering dual mechanisms of cell killing upon receptor-mediated endocytosis. The company said the dual-payload design is intended to address tumor heterogeneity and potential resistance to single-payload approaches. The specific identities of the two cytotoxic payloads have not been publicly disclosed.
The planned Phase I study will evaluate safety, tolerability, dose-limiting toxicities, pharmacokinetics, and preliminary anti-tumor activity in patients with unresectable or metastatic HCC. A dose-escalation portion is intended to characterize the safety profile and establish a recommended dose for subsequent development. Acepodia also submitted a separate IND application for ACE723 to China's National Medical Products Administration in August 2026 as part of a global development strategy for the program.