PIPELINE

Diversified pharmaceutical company with divisions
for novel medicines and complex generics

HOME PIPELINE ARBM-101

ARBM-101

TARGET INDICATION DEVELOPMENT STAGE
Copper Wilson’s disease IND-enabling studies
Preclinical stage :
- GLP-tox study is ongoing
- IND submission planned for 2Q 2025
- FIH study planned for 3Q 2025

ARBM-101

TARGET

Copper

INDICATION

Wilson’s disease

DEVELOPMENT STAGE

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

Summary

ARBM-101 is expected to prevent or stop WD liver damage from worsening by facilitating copper excretion as it was confirmed in a WD rat model. Its unprecedented de-coppering efficacy in WD animals presents its superior therapeutic potential that none of the currently available copper chelators can achieve.

The image modified from https://www.osmosis.org/learn/Wilson_disease

Mechanism of Action

ARBM-101 prevented or stopped the progression of copper-overloaded liver damage by eliminating excess copper from the liver into feces in WD rats. Such an efficacy is thought to bedriven by its enormously high affinity to copper and by its facilitation of excretion through bile.

Modified from Ala A. et al. 2007; The Lancet. & Patil M. et al. 2013; J. Clin. Exp. Hepatol. & Polishchuk E.V. et al. 2019; Gastroenterol.

Proof of Concept

A methanobactin peptide was shown to be superior to any other copper-chelating drugs or drug candidates in terms of the ability of reducing liver copper levels by facilitating excess copper excretion as shown in the remnant copper contents post treatment upon i.p. injections to WD rats (left panel). Methanobactins facilitate copper excretion through bile-fecal path as directly demonstrated by liver perfusion experiments (right panel). Such mode of action makes them markedly distinct from the currently marketed drugs such as D-PA or Trientine (TETA), both of which chelate blood copper, rendering chelated copper ions passively excreted into urine. It was also evident that methanobactins were superior to tetrathiomolybdate (TTM) in the excretion levels among those mainly taking bile-fecal path (right panel).

Lichtmannegger, J., et al., 2016; J. Clin. Invest.

Efficacy

Hepatocytic mitochondria were shown to recover their activities including their capability of producing ATP upon ARBM-101 treatment in a WD rat model (Data not shown). Although the mechanism of ARBM-101 rescuing mitochondrial function is still under investigation, it is certain that prompt elimination of excess copper from the cell by ARBM-101 allows mitochondria to recover their functionality leading to prevention of hepatocytic cell death and of liver disease progression.