Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 159

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 1
Chunk 159
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 $49.0 million in revenue from Sulanda, up from $43.9 million in 2023, as increasing brand awareness amongst doctors and improving NET diagnosis drove prescription growth and market share to 27% in 2024 (2023: 21%).

Table of Contents

4. Sovleplenib (HMPL-523)

Sovleplenib is a novel, selective, oral inhibitor targeting Syk, for the treatment of hematological malignancies and immune diseases. Syk is a component in Fc receptor and B-cell receptor signaling pathway. The threshold of safety for a Syk inhibitor in chronic disease is extremely high, with no room for material toxicity. The failure of Tavalisse in a global Phase III registration study in rheumatoid arthritis provided important insights for us in the area of toxicity. In addition, Tavalisse has also been shown to strongly inhibit the Ret kinase, and in pre-clinical trials it was demonstrated that inhibition of the Ret kinase was associated with developmental and reproductive toxicities. We own all rights to sovleplenib globally.

Sovleplenib Mechanism of Action

Syk is a key kinase upstream to PI3K δ and BTK within the B-cell signaling pathway and therefore thought to be an important target for modulating B-cell signaling. We believe it could deliver the same outcome as inhibitors of BTK and PI3K δ, assuming no unintentional toxicities are derived from Syk inhibition. The central role of Syk in signaling processes is not only in cells of immune responses but also in cell types known to be involved in the expression of tissue pathology in autoimmune, inflammatory and allergic diseases. Interfering with Syk could represent a possible therapeutic approach for treating these disorders. Several studies have shown Syk as a key player in the pathogenesis of rheumatoid arthritis, SLE and MS.

In hematopoietic cells, Syk is recruited to the intracellular membrane by activated membrane receptors like B-cell receptors or another receptor called Fc and then binds to the intracellular domain of the receptors. Syk is activated after being phosphorylated by certain kinases and then further induces downstream intracellular signals including B-cell linker, PI3K δ, BTK and Phospholipase C-y2 to regulate B-cell proliferation, growth, differentiation, homing, survival, maturation, and immune responses. Syk regulates lymphatic cells and signal transduction of non-lymphatic cells, resulting in different immunological functions such as