Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 437

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 4
Chunk 437
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O 2024. As of Dec 11, 2023, 47 patients with advanced solid tumors were enrolled. During the dose escalation from 5 to 75 mg, 5 patients experienced a dose-limiting toxicities of grade 3 dermatitis acneiform, rash and acute kidney injury. Partial response was seen in 1 patient with duodenal adenocarcinoma, 1 patient with endometrial cancer and 1 patient with NSCLC. 25 (53.2%) pts reported grade ≥3 TEAEs. The most common ≥ grade 3 TEAEs were rash (10.6%) and anemia (10.6%). RP2D was determined to be 50 mg OD.
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14. Amdizalisib (HMPL-689)
Amdizalisib is a novel, highly selective oral inhibitor targeting the isoform PI3Kδ, a key component in the B-cell receptor signaling pathway. We retains all rights to amdizalisib worldwide. Through discussions with the NMPA, it is clear that a randomized study is required to support registration. In view of the changing regulatory landscape, we are currently evaluating the clinical development plan and regulatory guidance before deciding the next strategy for amdizalisib.
Class I phosphatidylinositide-3-kinases (“PI3Ks”) are lipid kinases that, through a series of intermediate processes, control the activation of several important signaling proteins including the serine/threonine kinase AKT. In most cells, AKT is a key PI3Kδ affector that regulates cell proliferation, carbohydrate metabolism, cell motility and apoptosis and other cellular processes. Upon an antigen binding to B-cell receptors, PI3Kδ can be activated through the Lyn and Syk signaling cascade.
Aberrant B-cell function has been observed in immunological diseases and B-cell mediated malignancies. PI3Kδ is considered to be a promising target for hematologic cancer, autoimmunity and transplant organ rejection and other related inflammation diseases.
Compared to other PI3Kδ inhibitors, amdizalisib shows higher potency and selectivity.
Enzyme selectivity shows that amdizalisib is about five-fold more potent than Zydelig on whole blood level and, unlike Copiktra, does not inhibit PI3K-g.

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Enzyme IC50 (nM)                                  HMPL