Globenewswire·2025-12-17 00:00Core Insights - HUTCHMED has initiated a global Phase I clinical development program for HMPL-A251, a first-in-class PI3K/PIKK-HER2 Antibody-Targeted Therapy Conjugate, with the first patient dosed on December 16, 2025 [1][2] Group 1: Clinical Development - The Phase I/IIa study evaluates HMPL-A251 monotherapy in adult patients with unresectable, advanced or metastatic HER2-expressing solid tumors, focusing on safety, tolerability, and determining maximum tolerated doses [2][3] - The study is divided into two parts: Phase I for dose escalation and Phase IIa for dose expansion and optimization, with primary outcomes including safety and preliminary efficacy [2][3] Group 2: Product Details - HMPL-A251 is derived from HUTCHMED's next-generation ATTC platform, designed to deliver targeted pathway inhibition directly into HER2-expressing tumor cells, potentially overcoming systemic toxicity associated with traditional PI3K/PIKK inhibitors [3][4] - The ATTC platform combines monoclonal antibodies with small-molecule inhibitor payloads, aiming for synergistic anti-tumor activity and improved safety profiles compared to traditional therapies [5][6] Group 3: Mechanism of Action - The PI3K/AKT/mTOR (PAM) pathway is critical for cell growth and survival, with alterations linked to poor prognosis in various cancers; HMPL-A251 aims to address challenges faced by existing PAM-targeted drugs [7][8] - The innovative design of HMPL-A251 enhances targeted delivery to tumor cells, maximizing therapeutic benefits while minimizing systemic exposure [9]