Australian company Nyrada (ASX:NYR) says it has made major progress in the development of a small molecule PCSK9 inhibitor.
The company said a paper has been published in the international peer-reviewed journal, Bioorganic and Medicinal Chemistry, that shows it has successfully identified a small molecule that inhibits the production of PCSK9 in vitro and lowers total blood cholesterol levels in an animal model.
The paper is entitled ‘A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove.’
Companies have developed and commercialised injectable biologic inhibitors for the treatment of high cholesterol.
Amgen's REPATHA (evolocumab), which is currently reimbursed through the PBS for a small number of patients, was recently recommended for the treatment of hypercholesterolaemia in patients who are at very high risk of atherosclerotic cardiovascular disease. Sanofi is also commercialising a biologic PCSK9 inhibitor - PRALUENT (alirocumab).
“It is a tremendous achievement to have our PCSK9i science validated by our peers. The paper confirms that Nyrada PCSK9i compounds lower blood cholesterol levels in an in vivo model and restore LDL cholesterol capture by human cells.
"This provides proof-of-concept that a small molecule inhibitor against PCSK9 is therapeutically viable,” said publication co-author, Nyrada scientific advisory board member, Professor Gilles Lambert of Laboratoire Inserm, France.
“Overcoming this binding challenge with our PCSK9i drug candidate and having the results validated by the scientific community is a vital early step in protecting the commercial value of this asset,” said Nyrada CEO James Bonnar.
The company said the publication is the latest sign of progress in its strategy to develop an oral small molecule cholesterol-lowering drug for the estimated 40 per cent of patients who do not respond adequately to statins.
"A small-molecule PCSK9 inhibitor that can be combined with a statin opens the potential for a convenient and cost-effective ‘single pill’ therapy for high LDL cholesterol," said the company.
The company said the next step in the PCSK9 program is to confirm the lead candidate based on PCSK9-binding potency and oral bioavailability.