Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 433

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 4
Chunk 433
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 enroll at least 60 patients.
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10. HMPL-415
HMPL-415 is a novel, highly potent, selective and non-competitive SHP2 allosteric inhibitor. As of today, no SHP2 inhibitor drug has been approved. We retain all rights to HMPL-415 worldwide.
HMPL-415 Mechanism of Action
SHP2 modulates diverse cell signaling events that control metabolism, cell growth, differentiation, cell migration, transcription and oncogenic transformation. It interacts with diverse molecules in the cell, and regulates key signaling events including RAS/ERK, PI3K/AKT, JAK/STAT and PD-1 pathways downstream of several receptor tyrosine kinases (“RTKs”) upon stimulation by growth factors and cytokines. Dysregulation of SHP2 expression or activity causes many developmental diseases, and hematological and solid tumors.
HMPL-415 Pre-clinical Evidence
Pre-clinical data was presented at EORTC 2023 highlighting HMPL-415 as a potent, selective, and non-competitive SHP2 inhibitor with strong activity against multiple RAS/MAPK activated tumor models, including those with KRAS alterations, BRAF, NF1 and EGFT mutants. It showed prolonged and high tumor exposure with sustained pathway inhibition after repeat dosing. Strong anti-tumor efficacy was also seen with intermittent dosing (twice a week or once weekly).
HMPL-415 Clinical Development

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Treatment   ​   Patient Focus   ​   Sites   ​   Phase   ​   Status/Plan          ​   NCT #      
HMPL-415        Solid tumors        China       I           Initiated Jul 2023       NCT05886374
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Phase I study of HMPL-415 in advanced solid tumors (NCT05886374)
In July 2023, we initiated a China Phase I open-label study of HMPL-415 as a single agent in patients with advanced malignant solid tumors. This study is expected to enroll up to approximately 80 patients, including patients as part of the dose escalation stage, and further patients at the determined RP2D.
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11. HMPL-653
HMPL-653 is an investigational novel, highly selective, and potent CSF-1R inhibitor designed to target CSF