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Target Overview
Claudin 18 is a trans-membrane protein and is an important component of the tight junction complexes that regulate cell-cell adhesion, cell permeability, and cell polarity. Alternative splicing of Claudin 18 transcripts results in 2 isoforms: CLDN18.1, which is expressed in the lung and CLDN18.2, which is restricted to the gastric epithelium. In normal tissues, CLDN18.2 expression is restricted to the gastric mucosa. In tumor tissues, CLDN18.2 is widely overexpressed in a variety of cancers such as gastric cancer (GC), gastroesophageal junction cancer (GEJC), pancreatic ductal adenocarcinoma (PDAC), and adenocarcinoma of esophagus.1
Compound Overview
Sonesitatug vedotin (AZD0901) is an ADC that consists of a humanized monoclonal antibody against CLDN18.2, conjugated to a potent microtubule inhibitor, monomethyl auristatin E (MMAE) via a protease cleavable linker.
Sonesitatug vedotin is designed to target and deliver the cytotoxic agent, MMAE, inside cancer cells that express CLDN18.2 and reduce systemic exposure to the cytotoxic payload compared to the way chemotherapy is commonly delivered.
The released MMAE payload also exerts bystander antitumor activity through cytotoxic activity in both the target cells and neighboring tumor cells, owing to its high cell membrane permeability.
Mechanism of Action
References
1. Sahin U, Koslowski M, Dhaene K, et al. Clin Cancer Res. 2008;14(23):7624-7634.
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Abbreviations
5-FU
5-fluorouracil
ADC
antibody drug conjugate
CLDN18.1
Claudin 18.1 isoform
CLDN18.2
Claudin 18 isoform 2
FLOT
docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil
GEJ
gastroesophageal junction
MMAE
monomethyl auristatin E
T-DXd
fam-trastuzumab deruxtecan-nxki in US only; trastuzumab deruxtecan in other regions of world
Target Overview
Claudin 18 is a trans-membrane protein and is an important component of the tight junction complexes that regulate cell-cell adhesion, cell permeability, and cell polarity. Alternative splicing of Claudin 18 transcripts results in 2 isoforms: CLDN18.1, which is expressed in the lung and CLDN18.2, which is restricted to the gastric epithelium. In normal tissues, CLDN18.2 expression is restricted to the gastric mucosa. In tumor tissues, CLDN18.2 is widely overexpressed in a variety of cancers such as gastric cancer (GC), gastroesophageal junction cancer (GEJC), pancreatic ductal adenocarcinoma (PDAC), and adenocarcinoma of esophagus.1
Compound Overview
Sonesitatug vedotin (AZD0901) is an ADC that consists of a humanized monoclonal antibody against CLDN18.2, conjugated to a potent microtubule inhibitor, monomethyl auristatin E (MMAE) via a protease cleavable linker.
Sonesitatug vedotin is designed to target and deliver the cytotoxic agent, MMAE, inside cancer cells that express CLDN18.2 and reduce systemic exposure to the cytotoxic payload compared to the way chemotherapy is commonly delivered.
The released MMAE payload also exerts bystander antitumor activity through cytotoxic activity in both the target cells and neighboring tumor cells, owing to its high cell membrane permeability.
Mechanism of Action
References
1. Sahin U, Koslowski M, Dhaene K, et al. Clin Cancer Res. 2008;14(23):7624-7634.
Clinical trial information
Select trial for more information
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Abbreviations
5-FU
5-fluorouracil
ADC
antibody drug conjugate
CLDN18.1
Claudin 18.1 isoform
CLDN18.2
Claudin 18 isoform 2
FLOT
docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil
GEJ
gastroesophageal junction
MMAE
monomethyl auristatin E
T-DXd
fam-trastuzumab deruxtecan-nxki in US only; trastuzumab deruxtecan in other regions of world