Hehuang Pharmaceutical (00013) launches global clinical development of ATTC candidate HMPL-A251 for the treatment of solid tumors

Zhitong Finance App News, Hehuang Pharmaceutical (00013) issued an announcement to launch a global Phase I clinical development project for HMPL-A251. HMPL-A251 is the world's first PI3K/PIKK-HER2 antibody-targeted conjugation drug (“ATTC”). It consists of a highly selective and potent PI3K/PIKK inhibitor as payload (payload) and humanized anti-HER2 IgG1 antibody conjugated through a lyzable ligator (linker). Research will be carried out in the US and China. The first patient received the first dose of medication in China on December 16, 2025.

This first human trial is a phase I/IIa, open-label, multicenter clinical study to evaluate the use of HMPL-A251 as a single agent for the treatment of adult patients with unresectable, advanced or metastatic solid tumors with HER2 expression. The study was divided into two phases: phase I dose escalation phase and phase IIa dose expansion and optimization phase. The main indicators of the study were the safety and tolerability of HMPL-A251, determining the maximum tolerable dose (MTD) and/or recommended dose extension (RDE) in phase I, further evaluating safety and initial efficacy under RDE, and determining recommended doses for phase II (RP2D) or phase III (RP3D) clinical trials in phase IIa. Secondary indicators include initial antitumor activity, pharmacokinetic characteristics, and immunogenicity of HMPL-A251.

HMPL-A251 is the first drug candidate to enter clinical development under Hewang Pharmaceutical's next-generation ATTC platform. The platform's first drug candidates adopted potent and highly selective PI3K/PIKK inhibitors as payloads. By coupling this innovative payload with an anti-HER2 antibody, HMPL-A251 was designed to target HER2 expression tumor cells, and is expected to overcome the systemic toxicity and narrow treatment window that have long limited the use of PI3K/PIKK inhibitors. This strategy aims to improve overall tolerance while achieving more effective and long-lasting pathway inhibition.

Pre-clinical data on HMPL-A251 were presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targeting and Cancer Therapy. These data confirm the potential for translational application of the ATTC platform, support the ongoing global clinical evaluation of HMPL-A251, and demonstrate the broad potential of Huhuang Pharmaceutical's connector-payload combination based on PI3K/PIKK inhibitors, which is expected to derive a series of future ATTC drug candidates.