Core Viewpoint - Hutchison China MediTech Limited (HCM) is set to present preclinical data for HMPL-A251, a novel PI3K/AKT/mTOR (PAM)-HER2 antibody-drug conjugate (ATTC), at the AACR-NCI-EORTC International Conference on Molecular Targeted Therapy and Cancer Therapeutics in Boston from October 22 to 26, 2025 [1] Group 1: Product Overview - HMPL-A251 is designed to combine HER2-targeted therapy with PAM pathway inhibition, aiming to overcome the limitations of traditional antibody-drug conjugates (ADCs) and single PAM inhibitors [1] - The drug utilizes a highly selective and potent PI3K/PIKK inhibitor as the payload, conjugated to a humanized anti-HER2 IgG1 antibody via a cleavable linker [1] Group 2: Preclinical Efficacy - In vitro studies show that the PI3K/PIKK inhibitor payload exhibits strong, selective, and broad anti-tumor activity across 130 tumor cell lines [2] - HMPL-A251 demonstrates HER2-dependent anti-tumor activity, effectively inhibiting the growth of HER2-positive tumor cells regardless of PAM pathway alterations [2] - The compound also shows a bystander effect on HER2-negative cells when co-cultured with HER2-positive cells [2] Group 3: Safety and Efficacy - The ATTC design emphasizes the precise delivery of regulatory pathway-modulating payloads to tumor tissues, enhancing long-term safety compared to traditional cytotoxic ADCs [3] - HMPL-A251 outperforms naked antibodies and payload combination therapies in anti-tumor efficacy and tolerability in vivo [3] - The drug induces tumor regression in various models with a single intravenous injection, showing efficacy correlated with payload concentration and target inhibition [3] Group 4: Future Development Plans - HCM plans to initiate global clinical trials for HMPL-A251 by the end of 2025 and submit multiple global new drug clinical trial applications for other ATTC candidates in 2026 [4] - The ATTC platform represents a new generation of precision cancer therapies, combining monoclonal antibodies with proprietary targeted small molecule inhibitors for enhanced anti-tumor activity and safety [4][5]
和黄医药于AACR-NCI-EORTC分子靶向和癌症治疗国际会议上公布HMPL-A251数据