China-based HutchMed Ltd (NASDAQ: HCM; HKG: 0013) has announced the initiation of a Phase I clinical study for its investigational novel selective allosteric inhibitor, HMPL-415, which targets Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2). The trial, aimed at assessing the molecule in general solid tumors, marked its first patient dosing on July 6, 2023.
HMPL-415: A Potent and Selective SHP2 Inhibitor
HMPL-415 is a novel, highly potent, and selective allosteric SHP2 inhibitor. SHP2, a non-receptor protein tyrosine phosphatase, is widely expressed in the cytoplasm of various tissues and plays a crucial role in modulating diverse cell signaling events that control metabolism, cell growth, differentiation, cell migration, transcription, and oncogenic transformation. It interacts with multiple molecules within the cell and regulates key signaling pathways, including RAS/ERK, PI3K/AKT, JAK/STAT, and PD-1, which are downstream of several receptor tyrosine kinases (RTKs) upon stimulation by growth factors and cytokines. Dysregulation of SHP2 expression or activity is associated with various developmental diseases, including hematological and solid tumors. HutchMed retains all global rights to HMPL-415.
Domestic Competition in SHP2 Inhibitor Clinical Studies
Several domestic companies have conducted clinical studies for SHP2 inhibitors both domestically and internationally. These include InnoCare Pharma’s ICP-189, Genhouse bio’s GH21, Jacobio Pharma’s JAB-3312, Betta Pharma’s BPI-442096, and Hisun Pharma’s HS336. The initiation of HutchMed’s Phase I study for HMPL-415 adds to the competitive landscape of SHP2 inhibitor development, highlighting the active pursuit of novel therapeutics in the oncology space.-Fineline Info & Tech
