HUTCHMED (China) Limited (13) has announced new preclinical results for HMPL-A251 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held in Boston, USA, from October 22 to 26, 2025. The investigational candidate marks the first offering from the company’s Antibody-Targeted Therapy Conjugate (「ATTC」) platform.

According to the announcement, HMPL-A251 combines a selective PI3K/PIKK inhibitor payload with a humanized anti-HER2 IgG1 antibody via a cleavable linker. It is designed to bolster efficacy and mitigate toxicities often associated with conventional cytotoxin-based antibody-drug conjugates. Preclinical studies revealed strong antitumor activity and tolerability, with a single intravenous dose inducing tumor regression in HER2-positive and HER2-low models, including those exhibiting PAM pathway alterations.

Data also show features such as bystander killing and promising safety indicators, attributed to low plasma exposure of the free payload. Comparisons with an approved HER2-directed ADC in certain models demonstrated either superior or comparable efficacy at equivalent doses.

The company plans to initiate global clinical trials for HMPL-A251 around the end of 2025 and pursue multiple additional international filings for further ATTC candidates in 2026. Management indicates that these results could potentially expand therapeutic options for a range of tumor types through targeted delivery and enhanced safety. HUTCHMED continues to focus on advancing this platform toward clinical development, aiming to combine selectivity and precision in oncology treatments.