Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 170

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 1
Chunk 170
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 (PD-1) in patients with specific advanced or metastatic solid tumors. The first stage of the study is a dose escalation phase to determine DLT and RP2D. The second stage is a dose expansion phase in solid tumor patients with either GC, IHCC or urothelial carcinoma harboring specific FGFR gene alterations.

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7. Ranosidenib (HMPL-306)

Ranosidenib is a novel dual-inhibitor of IDH1 and IDH2 enzymes. IDH1 and IDH2 mutations have been implicated as drivers of certain hematological malignancies, gliomas and solid tumors, particularly among acute myeloid leukemia patients, with approximately 20% of patients having mutant IDH genes. IDH mutations also occurred in myelodysplastic syndrome (“ MDS”), myeloproliferative neoplasms (“ MPNs”), low-grade glioma and intrahepatic cholangiocarcinoma. We retain all rights to ranosidenib worldwide.

Ranosidenib Mechanism of Action

IDHs are critical metabolic enzymes that help to break down nutrients and generate energy for cells. When mutated, IDH creates a molecule, 2-hydroxyglutarate (“2-HG”), that alters the cell’ s genetic programming and prevents cells from maturing. Accumulation of 2-HG into cells causes activation of oncogenes and deactivation of tumor-suppressor genes. 2-HG affects different transcription factors, such as hypoxia-inducible factor (“ HIF”) and mammalian target of rapamycin (“ mTOR”), which are commonly deregulated in cancer. Elevation of 2-HG levels can be used as a marker of target engagement by an IDH inhibitor. Cytoplasmic mutant IDH1 and mitochondrial mutant IDH2 have been known to switch to the other form when targeted by an inhibitor of IDH1 mutant alone or IDH2 mutant alone. By targeting both IDH1 and IDH2 mutations, ranosidenib could potentially benefit cancer patients harboring either IDH mutation and may address acquired resistance to IDH inhibition through isoform switching.

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Ranosidenib Clinical Development

  Treatment        Trial Name, Patient Focus                           Sites       Phase      Status/Plan                 NCT #        
  Ranosidenib      RAPHAEL: r/r mIDH1/2 AML                            China       III        Ongoing since May 2024