Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 178

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 1
Chunk 178
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 is ubiquitously expressed on virtually all human cells. The overexpression of CD47 is reported in a variety of tumors and is believed to be associated with immune escape from macrophage-mediated phagocytosis. HMPL-A83 blocks CD47 binding to Signal regulatory protein α (“ SIRP α”) and disrupts the “do not eat me” signal that cancer cells use to shield themselves from the immune system.

HMPL-A83 Pre-clinical Evidence

In preclinical studies, HMPL‑ A83 demonstrated a high affinity for CD47 antigen on tumor cells and strong phagocytosis induction of multiple tumor cells, as well as weak affinity for red blood cells and no induction of hemagglutination, implying low risk of anemia, a potential event of special interest. HMPL-A83 demonstrated strong anti-tumor activity in multiple animal models.

HMPL-A83 Clinical Development

  Treatment      Patient Focus                     Sites      Phase      Status/Plan      NCT #        
  HMPL-A83       Advanced malignant neoplasms      China      I          Ongoing          NCT05429008  
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Phase I study of HMPL-A83 in advanced solid tumors (NCT04908046)

In July 2022, we initiated a China Phase I open-label study of HMPL-A83 in patients with advanced malignant neoplasms. The primary endpoints are dose-limiting toxicity, safety, tolerability, RP2D and maximum tolerated dose.

Table of Contents

13. HMPL-295

HMPL-295 is a novel, potent and selective ERK inhibitor. ERK is a downstream component of the RAS-RAF-MEK-ERK signaling cascade (“ MAPK pathway”). This is first of our multiple candidates in discovery addressing the MAPK pathway. We retain all rights to HMPL-295 worldwide.

HMPL-295 Mechanism of Action

MAPK pathway is dysregulated in cancer, in which mutations or nongenetic events hyper-activate the pathway in up to 50% of cancers. RAS and RAF mutations predict worse clinical prognosis in a wide variety of tumor types, mediate resistance to targeted therapies, and decrease the response to the approved standards of care, namely, targeted therapy and immunotherapy. ERK inhibition has the potential to overcome or avoid the intrinsic or acquired resistance from the inhibition of RAS, RAF and MEK upstream mechanisms. HMPL-295 inhibited