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ARBM-201

TARGET INDICATION DEVELOPMENT STAGE
Pendrin, PDS ARDS
(Acute Respiratory Distress Syndrome)		 IND-enabling studies
Preclinical stage :
- GLP-tox study planned for 1H 2025
- IND submission planned for 2H 2025
- FIH study planned for 1Q 2026

ARBM-201

TARGET

Pendrin, PDS

INDICATION

ARDS
(Acute Respiratory Distress Syndrome)

DEVELOPMENT STAGE

IND-enabling study
Preclinical stage :
- GLP-tox study planned for 4Q 2022
- IND submission planned for 4Q 2023
- FIH study planned for 1Q 2024

Summary

ARBM-201 has shown a therapeutic potential to treat acute lung injury (ALI) by reducing the expression of pendrin and its anion exchange activity in the alveolar epithelial cells and blocking the downstream signaling pathway and inflammation, as confirmed in an LPS-induced ALI mice model. Since the pendrin expression is increased in both LPS-treated mouse airways and patients with ARDS caused by pneumonia, it strongly suggests a high possibility for the clinical application of pendrin inhibitor (ARBM-201) in inflammatory airway disease.

Mechanism of Action

ARBM-201 is a new chemical entity with high selectivity for the SLC26A4 gene, which encodes a protein called pendrin. As a pendrin inhibitor, ARBM-201 binds to pendrin, blocks the transepithelial transport of SCN- and then inhibits OSCN- generation and NF-κB activation, which results in the suppression of proinflammatory cytokine production, neutrophil infiltration and subsequent lung injury.

Modified from Lee, E. H., et al., 2020; Theranostics.

Proof Of Concept

Pendrin expression level increased in LPS-treated mouse airways and also in BALF from pneumonia-induced ARDS patients (Figure 1). While the total cell count and protein concentration in bronchoalveolar lavage fluid was markedly increased after LPS treatment in the wild-type mice, they did not in pendrin-null mouse (Figure 2). In addition, simultaneous application of NaSCN with LPS-induced robust lung injury in pendrin-null mice, whereas administration of LPS alone did not induce ALI (Figure 3). These data strongly indicate the critical role of pendrin in ALI/ARDS pathogenesis and that airway surface SCN- transported by pendrin is an essential component for LPS-induced airway inflammation.

Lee, E. H., et al., 2020; Theranostics.

Efficacy

Treatment of pendrin inhibitor after LPS administration significantly reduced BALF total cell count and protein concentration, lung injury score, phospho-IκB protein expression, as well as proinflammatory cytokine levels in the LPS-induced ALI mice model.

Lee, E. H., et al., 2020; Theranostics.