LOXL2 Inhibitors

LOXL2 inhibitors for multiple indications

The LOXL2 enzyme is fundamental to the fibrotic cascade that follows chronic inflammation in the liver disease NASH, cardiac fibrosis, kidney fibrosis, and idiopathic pulmonary fibrosis (IPF), and it also plays a role in some cancers.

The Pharmaxis drug discovery group has developed two selective small molecule inhibitors to the LOXL2 enzyme from its amine oxidase chemistry platform. Extensive pre‐clinical showed the compounds displayed all the characteristics of a successful oral drug showing excellent efficacy in several different in vivo fibrosis models including fibrosis of the liver, lung, kidney and heart. Over the course of 2019 Pharmaxis scientists and collaborators demonstrated the link between LOXL2 inhibition in diseased organs, a reduction in collagen crosslinking in fibrotic tissue and clinical effect as measured by the area of fibrosis. The LOXL2 inhibitors have subsequently completed 3 month toxicology studies.

In phase 1 studies completed in 2019, doses of the drugs that resulted in 85% or greater inhibition over 24 hours of the target enzyme were significantly below the Human Equivalent No Observed Adverse Effect Level doses in all toxicity studies, demonstrating an adequate safety margin to start phase 2 studies of at least 3 months in length. (read more here) Further progressing the program in the first quarter of 2020, Pharmaxis completed a small phase 1 study that demonstrated an improved pharmacokinetic profile in a number of different dosing regimens.

Pharmaxis is currently pursuing a number of different partnering options to enable the drug to enter the clinic in phase 2 trials. While the process has taken longer than originally expected, and much of the industry focus has been on the Covid-19 pandemic, the Company continues to have discussions with a number of potential partners. Pharmaxis will provide more information when the process concludes.

The LOXL2 program has been conducted in collaboration with UK biotechnology company Synairgen plc (LSE: SNG).

Access Pharmaxis Publications and Posters on LOXL2 inhibitors

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Fibrosis

Phase I
Description Phase 1 clinical trial - first compound
Sites Two phase 1 units in Australia
Subjects Single Ascending Dose stage: 48; Multiple Ascending Dose stage: 24
Status Complete
More Information
Media Releases
Phase I
Description Phase 1 clinical trial - second compound
Sites Two phase 1 units in Australia
Subjects Single Ascending Dose stage: 48; Multiple Ascending Dose stage: 24
Status Complete
More Information
Media Releases