Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 167

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 1
Chunk 167
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MPHONY-1 study for 2L+ FL

Table of Contents

6. Fanregratinib (HMPL-453)

Fanregratinib is a novel, selective, oral inhibitor targeting FGFR 1/2/3. Aberrant FGFR signaling is associated with tumor growth, promotion of angiogenesis, as well as resistance to anti-tumor therapies. Approximately 10-15% of IHCC patients have tumors harboring FGFR2 fusion. We retain all rights to fanregratinib worldwide.

Fanregratinib Mechanism of Action

FGFR belongs to a subfamily of receptor tyrosine kinases. Four different FGFRs (FGFR1-4) and at least 18 ligand FGFs constitute the FGF/FGFR signaling system. Activation of the FGFR pathway through the phosphorylation of various downstream molecules ultimately leads to increased cell proliferation, migration and survival. FGF/FGFR signaling regulates tissue development, angiogenesis, and tissue regeneration. A growing body of evidence has demonstrated the oncogenic potential of FGFR aberrations in driving tumor growth, promoting angiogenesis, and conferring resistance mechanisms to oncology therapies. Dysfunction in the FGF/FGFR signaling leads to a number of developmental disorders and is consistently found to be a driving force in cancer. Deregulation of the FGFR can take many forms, including receptor amplification, activating mutations, gene fusions, and receptor isoform switching, and the molecular alterations are found at relatively low frequencies in most tumors.

Incidence of FGFR aberrations in various tumors

             Gene amplification                 Gene translocation                            Gene mutation                        
  FGFR1      Lung squamous (7-15%)              Lung squamous (n/a)                           Gastric (4%)                         
             H& N squamous (10-17%)             Glioblastoma (n/a)                            Pilocytic astrocytoma (5-8%)         
 ───────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
             Esophageal squamous (9%)           Myeloproliferative syndrome (n/a)                                                  
             Breast (10-15%)                    Breast (n/a)                                                                       
  FGFR2      Gastric (5-10%)                    Intra-hepatic biliary tract cancer (14%)      Endometrial (12-14%)                 
             Breast (5-10%)                     Breast (n/a)