Company: HMDCF
Filing Date: 2025-03-19
Form Type: 20-F
Source: 0001410578-25-000377
Chunk: 435

Company: HUTCHMED (China) Ltd
Filing Date: 2025-03-19
Form: 20-F
Item: Item 4
Chunk 435
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, tolerability, RP2D and maximum tolerated dose.
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12. HMPL-A83
HMPL-A83 is an investigational IgG4-type humanized anti-CD47 monoclonal antibody that exhibits high affinity for CD47. There is no approved anti-CD47 antibody. We retain all rights to HMPL-A83 worldwide.
HMPL-A83 Mechanism of Action
CD47 is a cell surface transmembrane protein that 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 (“SIRPα”) 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)
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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.

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