Pre-clinical data from Patrys’ study with Yale confirms PAT-DX1 targets and kills brain cancer stem cells

Therapeutic antibody developer Patrys (ASX: PAB) has published a further round of pre‐clinical data for its drug candidates PAT-DX1 and PAT‐DX1‐NP – a humanized version of the 3E10 anti‐DNA antibody that aims to reduce cancerous brain tumours (glioblastomas).

Dr James Hansen and Dr Jiangbing Zhou of the Yale School of Medicine have confirmed that PAT‐DX1 and PAT‐DX1‐NP were successful at targeting “tumour spheres” that were originally derived from human glioblastoma cancer stem cells (CSCs).

According to the team leading the study, treatment with PAT‐DX1‐NP showed significantly increased localisation to the CSC tumour spheres compared to unconjugated nanoparticles.

Patrys reports that PAT‐DX1‐NP penetrated into the centre of the tumour spheres and targeted cells inside the spheres as well as cells on the sphere surface. Follow‐on experiments showed that unconjugated PAT‐DX1 significantly reduced the growth and viability of the CSC tumour spheres.

“Patrys has previously shown that both PAT‐DX1 and PAT‐DX1‐NPs can cross the blood-brain barrier in a mouse model of glioblastoma, and confirmation that PAT‐DX1 targets and kills primary human glioblastoma stem cell tumour spheres in vitro is another exciting development,” said Dr James Campbell, CEO and managing director of Patrys.

Dr Campbell added that this newly published data “strengthens the case for glioblastoma as a development path for the DX1 technology.”

With encouraging results in hand and the study at Yale progressing as expected, Dr Campbell says that this new observation sets the scene for Patrys’ research plan with the Yale School of Medicine to test PAT‐DX1 in a proxy for the current human therapy regime for glioblastoma.

“This study will involve combinations of PAT‐DX1, temozolomide and radiation therapy, and evaluation of the single and combined effects on tumour size and survival. Data from this study is due in Q4 2018, and will inform possible clinical studies in glioblastoma,” said Dr Campbell.

Earlier this month, Patrys announced it was initiating a research and development collaboration bringing together experts from Yale School of Medicine in New Haven, Connecticut and Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts.

The newly-forged opportunity to further investigate PAT‐DX1 in an immunocompetent mouse model follows on from a successful PAT‐DX1 orthotopic glioblastoma study completed at Yale University in March.

Earlier this year, researchers showed that glioblastoma tumours in mice treated with PAT‐DX1 were more than 40% smaller than the comparable tumours in control mice.

According to Patrys, PAT-DX1 has shown “significant ability to kill cancer cells” in human tumour explants, xenograft and orthotopic models. Treatment with PAT‐DX1 has been shown to significantly improve survival in an orthotopic model of glioblastoma with the company continuing its study and likely to publish further results later this year.