Globenewswire·2025-10-23 00:00Core Insights - HUTCHMED announced preclinical data for HMPL-A251, a first-in-class PI3K/AKT/mTOR-HER2 Antibody-Targeted Therapy Conjugate, at the AACR-NCI-EORTC International Conference, showcasing its potential in cancer treatment [1][5] Summary by Sections Drug Candidate Overview - HMPL-A251 utilizes HUTCHMED's ATTC technology platform to create targeted therapy payloads while reducing associated toxicities [1] - The drug is designed to exploit the advantages of antibody-conjugates, featuring a highly potent PI3K/PIKK inhibitor payload linked to a humanized anti-HER2 IgG1 antibody [1][2] Mechanism of Action - The PI3K/PIKK inhibitor payload demonstrated high potency and selectivity across 130 tumor cell lines, inducing apoptosis in HER2-positive cells regardless of PAM pathway alterations [3] - HMPL-A251 showed a bystander effect on HER2-null cells when co-cultured with HER2-positive cells, indicating its broad anti-tumor activity [3] Efficacy and Safety - In vivo studies revealed that HMPL-A251 had superior anti-tumor efficacy and tolerability compared to traditional naked antibodies and payloads [4] - A single intravenous dose of HMPL-A251 led to tumor regression in various models, with efficacy correlating strongly with payload concentration and target inhibition [4] Comparison with Existing Treatments - When compared to T-DXd (trastuzumab deruxtecan), HMPL-A251 achieved superior or comparable efficacy at equivalent doses in most tested models [4] - The plasma exposure of free payload was significantly lower than for HMPL-251, suggesting reduced toxicity [4] Future Development Plans - HUTCHMED plans to initiate global clinical trials for HMPL-A251 by the end of 2025, with additional Investigational New Drug filings for more ATTC candidates in 2026 [5] ATTC Platform Insights - The ATTC platform represents a next-generation approach to precision oncology, combining monoclonal antibodies with small-molecule inhibitor payloads for enhanced anti-tumor activity and safety [6][7] - This platform aims to overcome challenges associated with traditional small-molecule inhibitors and improve long-term safety and efficacy in cancer treatments [7] Company Background - HUTCHMED is a commercial-stage biopharmaceutical company focused on the discovery and development of targeted therapies and immunotherapies for cancer and immunological diseases [8]