Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 179

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 1
Chunk 179
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 ribosomal S6 kinase (“ RSK”) phosphorylation which is a downstream signaling molecule regulated by ERK1/2 and stimulated by phorbol 12-myristate 13-acetate (“ PMA”).

HMPL-295 Pre-clinical Evidence

Pre-clinical data was presented at AACR 2024 highlighting strong activity against multiple MAPK pathway activated tumor models. HMPL-295 inhibited ERK1 kinase with IC50 of 4 ± 0.04 nM and ERK2 kinase with IC50 of 4 ± 1 nM. Selectivity against a panel of 394 kinases show≥20 folds selectivity over 384 kinases at 1 µm and <35% inhibition of 86 safety-related proteins at 1 µm. It effectively blocked ERK signaling and attenuated the growth of MAPK pathway dysregulated cancer cell lines. Combination significantly improved anti-tumor activity of targeted agents (e. g., adagrasib, encorafenib and cetuximab) and chemotherapy (e. g., gemcitabine, nab-paclitaxel, fluorouracil and irinotecan) in multiple tumor models with KRAS or BRAF mutation.

HMPL-295 Clinical Development

  Treatment      Patient Focus      Sites      Phase      Status/Plan         NCT #        
  HMPL-295       Solid tumors       China      I          Data presented      NCT04908046  
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Phase 1 dose-escalation study of HMPL-295 in advanced solid tumors (NCT04908046)

In July 2021, we initiated China Phase I open-label study of HMPL-295 in patients with advanced malignant solid tumors who have failed standard therapy. Following the initial dose escalation stage, another 10 to 15 patients would be enrolled at the RP2D to further evaluate its safety and the preliminary efficacy of HMPL-295. An exploratory study on the pharmacokinetic biomarkers of HMPL-295 was also planned.

Data was presented at ASCO 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 adenocarc