A new small molecule inhibitor of the LOXL2 enzyme, developed by Pharmaxis, is safe and holds potential to treat fibrotic diseases such as idiopathic pulmonary fibrosis (IPF) and non‐alcoholic steatohepatitis (NASH), according to results from a Phase 1 trial.
The study (ACTRN12617001564347) enrolled 48 healthy volunteers who were randomly assigned to one of six groups to receive a single dose of PXS-5382A — ranging between 5 and 200 mg — or a placebo. This was followed by a multiple ascending dose study, which was conducted in 24 healthy people who received a single daily dose of either 50, 100, or 200 mg doses of PXS-5382A or placebo for 14 days.
Results showed that PXS-5382A was well-tolerated, and had an acceptable safety profile with no significant adverse events being reported.
A detailed analysis of the investigational inhibitor revealed it is stable upon administration, achieving more than 85% inhibition of LOXL2 enzyme over 24 hours in the group of patients who were treated with 100 mg daily of PXS-5382A.
These positive clinical results demonstrate the potential of this new compound, supporting evidence found in previous preclinical studies.
Additionally, these findings further support the drug discovery technology of Pharmaxis, which also announced similar Phase 1 results for its first LOXL2 inhibitor, PXS-5338K, in October.
LOXL2 belongs to a family of important proteins involved in the construction of critical structures that support tissues and organs. The enzyme was found to play a key role in the development of IPF by helping to promote lung tissue scarring.
“Several large pharma companies are interested in the Pharmaxis program where both of our LOXL2 inhibitors have now successfully completed Phase 1 studies and demonstrated a best in class profile with 24‐hour inhibition of the target enzyme from a single daily dose,” Gary Phillips, CEO of Pharmaxis, said in a press release.
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“In a further significant scientific advancement we have also managed to underline the relevance of the program to potential partners by using our proprietary research tools to confirm that our compounds directly inhibit the activity of the raised levels of LOXL2 seen in diseased tissue from NASH and IPF animal models,” he added.
Based on these positive safety and early efficacy data, additional toxicity studies are being conducted and are expected to be completed within three months. Upon completion of these additional studies, the company is planning to start a final series of scientific briefings to potential partners, Phillips announced.
This move precedes anticipated commercial partnering discussions to achieve a licensing agreement for the company’s two LOXL2 inhibitors in 2019.