SSAO Inhibitor (PXS-4728)

Novel SSAO/VAP-1 inhibitor PXS-4728 (also known as BI 1467335) - for the treatment of inflammation

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.

PXS-4728 is efficacious in various pre-clinical NASH and lung inflammation models. The inhibition of SSAO can be easily measured with biomarkers and exhibits therapeutic potential across a range of chronic inflammatory conditions.

PXS-4728 was sold to Boehringer Ingelheim (BI) in 2015, initially to develop for the treatment of the liver-related disease Nonalcoholic Steatohepatitis (NASH) and subsequently for diabetic retinopathy (DR). Under the sale agreement Boehringer was responsible for all development, regulatory, manufacturing and commercialisation activities with milestone and other payments to Pharmaxis in relation to the development and approval of PXS-4728 in two indications. Pharmaxis received an upfront payment of €27.5 million (approximately A$39m) and a further €28 upon commencement of phase 2a clinical trials in NASH and DR - a total of A$83 million received from BI over the five years of its development program. The program was discontinued by BI in September 2020 primarily because of the risk of dose dependent drug interactions of the compound identified in a separate Phase I study.

The full program as developed by BI is in the process of being returned to Pharmaxis, including the extensive preclinical, clinical, safety and regulatory work carried out by BI. Pharmaxis will review the bank of data collected in more detail and evaluate potential opportunities in other indications that already have supportive pre-clinical data and where the risk of drug interactions are of less concern. Pharmaxis has the right to have the program returned from BI at no cost.

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