Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 155

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 1
Chunk 155
---
1R kinases with IC50in a range of 1 nM to 24 nM. It blocked VEGF-induced VEGFR2 phosphorylation in HEK293 cells and CSF-1R phosphorylation in RAW264.7 cells with an IC50of 2 nM and 79 nM, respectively. Surufatinib also reduced VEGF- or FGF-stimulated human umbilical vein endothelial cell proliferation with an IC50< 50 nM. In animal studies, a single oral dose of surufatinib inhibited VEGF-stimulated VEGFR2 phosphorylation in lung tissues of nude mice in an exposure-dependent manner. Elevation of FGF23 levels in plasma 24 hours post dosing suggested suppression of FGFR signaling. Surufatinib demonstrated potent tumor growth inhibition in multiple human xenograft models and decreased cluster of differentiation 31 expression remarkably, suggesting strong inhibition on angiogenesis through VEGFR and FGFR signaling.

In a syngeneic murine colon cancer model, surufatinib demonstrated moderate tumor growth inhibition after single-agent treatment. Flow cytometry and immunohistochemistry analysis revealed an increase of certain T cells and a significant reduction in certain tumor-associated macrophages, including CSF-1R mutation positive tumor-associated macrophages in tumor tissue, indicating surufatinib has a strong effect on CSF-1R. A combination of surufatinib with a PD-L1 antibody resulted in enhanced anti-tumor effect. These results suggested that surufatinib has a strong effect in modulating angiogenesis and cancer immunity.

Table of Contents

Surufatinib Clinical Development

  Treatment                                 Trial Name, Patient Focus         Sites      Phase       Status/Plan                     NCT #        
  Surufatinib + Airuika + chemotherapy      1L PDAC                           China      II/III      Fully enrolled Phase II         NCT06361888  
  Surufatinib                               SANET-ep: Non-pancreatic NET      China      III         Approved; Launched in 2021      NCT02588170  
  Surufatinib                               SANET-p: Pancreatic NET           China      III         Approved; Launched in 2021      NCT02589821  
 ──────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────

Surufatinib Combination - Pancreatic Cancer

Phase II/III study of sur