SSAO Inhibitor (PXS-4728)

Novel SSAO/VAP-1 inhibitor PXS-4728 - for the treatment of inflammation and Parkinson's disease

PXS-4728 is a very potent and highly selective compound. It is a first-in-class, mechanism-based inhibitor of Semicarbazide-Sensitive Amine Oxidase (SSAO), also known as Vascular Adhesion Protein-1 (VAP-1), or Amine Oxidase Copper Containing 3 (AOC3), PXS-4728 and provides greater than 90% inhibition of its target enzyme for 24 hours after a single oral dose.

The inhibition of SSAO can be easily measured with biomarkers and exhibits therapeutic potential across a range of chronic inflammatory conditions.

Pharmaxis is exploring the potential of PXS-4728 in diseases where neuro inflammation plays a role and in September 2022 secured £2.9m (~A$5m) in funding from Parkinson’s UK to conduct a phase 2 clinical trial of PXS-4728 in Parkinson’s disease. The study is being carried out by Pharmaxis in collaboration with researchers at the Universities of Oxford and Sydney.

The study will recruit patients with isolated Rapid Eye Movement Sleep Behaviour Disorder (iRBD), a strong predictor of Parkinson’s, to evaluate whether PXS‐4728 can reduce neuroinflammation with results measured by nuclear imaging of the brain.

PXS-4728 has already been the subject of an extensive development program, conducted following a 2015 deal with Boehringer Ingelheim (BI). The asset was shown to be efficacious in pre-clinical work in Nonalcoholic Steatohepatitis (NASH) and subsequently for diabetic retinopathy (DR). However, the program was discontinued by BI in September 2020 primarily because of an off-target effect on an additional inflammatory enzyme in the brain, MAO-B (monoamine oxidase B).

It was identification of this effect - and the significant body of research work underpinning PXS-4728 - which has sparked the quest to explore its potential in brain diseases, attracting the funding from Parkinson’s UK and interest from international universities.

The inhibition of SSAO can be easily measured with biomarkers and exhibits therapeutic potential across a range of chronic inflammatory conditions.

Pharmaxis is exploring the potential of PXS-4728 in diseases where neuro inflammation plays a role and in September 2022 secured £2.9m (~A$5m) in funding from Parkinson’s UK to conduct a phase 2 clinical trial of PXS-4728 in Parkinson’s disease. The study is being carried out by Pharmaxis in collaboration with researchers at the Universities of Oxford and Sydney.

The study will recruit patients with isolated Rapid Eye Movement Sleep Behaviour Disorder (iRBD), a strong predictor of Parkinson’s, to evaluate whether PXS4728 can reduce neuroinflammation with results measured by nuclear imaging of the brain.

PXS-4728 has already been the subject of an extensive development program, conducted following a 2015 deal with Boehringer Ingelheim (BI). The asset was shown to be efficacious in pre-clinical work in Nonalcoholic Steatohepatitis (NASH) and subsequently for diabetic retinopathy (DR). However, the program was discontinued by BI in September 2020 primarily because of an off-target effect on an additional inflammatory enzyme in the brain, MAO-B (monoamine oxidase B).

It was identification of this effect - and the significant body of research work underpinning PXS-4728 - which has sparked the quest to explore its potential in brain diseases, attracting the funding from Parkinson’s UK and interest from international universities.

NASH

Diabetic retinopathy

Inflammation

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