Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 434

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 4
Chunk 434
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-1R driven tumors as a monotherapy or in combination with other drugs. Currently there are three FDA-approved CSF-1R for TGCT, chronic graft-versus-host disease, but none are approved in China. We retain all rights to HMPL-653 worldwide.
HMPL-653 Mechanism of Action
CSF-1R is usually expressed on the surface of macrophages and can promote growth and differentiation of macrophages. Studies have shown that blocking the CSF-1R signaling pathway could effectively modulate the tumor microenvironment, relieve tumor immunosuppression, and synergize with other anti-cancer therapies such as immune checkpoint inhibitors to achieve tumor inhibition. It has been demonstrated in several clinical studies that CSF-1R inhibitors could treat TGCT and treat a variety of malignancies combined with immuno-oncology or other therapeutic agents. 
HMPL-653 Pre-clinical Evidence
Pre-clinical data was presented at EORTC 2023 showing single agent anti-tumor activity in CSF-1/CSF-1R dependent tumor models. HMPL-653 prevented M2 macrophage polarization in a concentration-dependent manner, with dose-dependent tumor regression in tumor models with CSF-1R alterations at dose of 2.5 mg/kg or above. HMPL-653, administered once daily from 1 mg/kg to 10 mg/kg were well tolerated, and exhibited dose-dependent anti-tumor activities. It also showed enhanced response when administered in combination with anti-PD-1 antibody by decreasing tumor-infiltrating M2 macrophages and increasing the ratio of M1/M2 macrophages.
HMPL-653 Clinical Development
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Treatment       Patient Focus                 Sites       Phase       Status/Plan          NCT #      
HMPL-653        Solid tumors &amp; TGCT       China       I           Fully enrolled       NCT05277454
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Phase I study of HMPL-653 in advanced solid tumors (NCT05277454)
In January 2022, we started China Phase I open-label, single-arm study of HMPL-653 in patients with advanced or metastatic solid tumors and TGCT. Approximately 110 patients are expected to be enrolled in the dose escalation and expansion phase of this study. The primary endpoints are dose limiting toxicity, safety