Patrys' PAT-DX1 novel mechanism for crossing the blood brain barrier confirmed

Latest News

Australian company Patrys (ASX:PAB), a therapeutic antibody development company, has announced new pre-clinical data for its lead candidate, PAT-DX1.

The company said the studies provide "critical mechanistic data" that explain PAT-DX1’s ability to cross the blood-brain barrier (BBB) via the equilibrative nucleoside transporter 2 (ENT2) pathway.

"This data will support Patrys’ planned Investigational New Drug (IND) filing to clinically test PAT-DX1 against brain tumours and metastases as well as other cancers," said the company.

According to CEO and managing director Dr James Campbell, “It is well known that the human BBB prevents antibodies and the majority of small molecule therapeutics from entering the central nervous system.

"However, PAT-DX1 has proven to be an exception to this rule and has shown activity against brain tumours in mouse models of glioblastoma and triple negative breast cancer brain metastases.

"The study data clearly illustrates how PAT-DX1 is able to achieve these outcomes, and provides compelling evidence of an ENT2-mediated method of BBB penetration by PAT-DX1.

"The ability to explain PAT-DX1’s entirely new and highly effective mechanism of action supports our plans to advance to IND filing and commence clinical studies, together with enhancing partnering discussions.”

The investigation was conceived, designed and led by Dr James Hansen and Dr Jiangbing Zhou of the Yale School of Medicine.

The company said they initially completed an in vitro study that highlighted ENT2’s role in transporting PAT-DX1 across a model of the human BBB and showed co-treatment with a small molecule inhibitor of ENT2 blocks this transport.

A transwell membrane model (composed of human brain endothelial cells and normal human astrocytes adhered to a membrane) tested the ability of PAT-DX1 to cross the BBB in the presence or absence of an ENT2 inhibitor.

"In absence of the ENT2 inhibitor, PAT-DX1 crossed the BBB efficiently, while other molecules of similar molecular weight were blocked," said the company.

"The addition of the ENT2 inhibitor significantly impaired PAT-DX1 transport across the BBB, demonstrating that PAT-DX1 crosses the BBB via the ENT2 pathway.

"Following this finding, Dr Hansen and Dr Zhou completed a new animal study that confirmed that PAT-DX1 crosses the BBB and localises to orthotopic brain tumours in mice, and that co-treatment of mice with a small molecule inhibitor of ENT2 blocks this activity."

Patrys said the new study contributes to efforts to identify and optimise mechanisms of action for PAT-DX1. The study data strengthens the planned IND filing, provides biologic rationale to advance PAT-DX1 to commence clinical testing, particularly against brain tumours and metastases, and forms part of the data package that underpins future strategic discussions.