Ann: PAT-DX1 Targets and Kills Brain Cancer Stem Cells, page-2

ASX & Media Release
PAT-DX1 Targets and Kills Brain Cancer Stem Cells
Melbourne, Australia; May 31, 2018: Patrys Limited (ASX: PAB), a therapeutic antibody development company, is pleased to announce further pre‐clinical data for its drug candidates PAT‐ DX1 and PAT‐DX1‐NP. PAT‐DX1 is Patrys’ humanized version of the 3E10 anti‐DNA antibody, while PAT‐DX1‐NP links PAT‐DX1 to nanoparticles (NPs) that can be loaded with chemotherapeutic (or other) drugs.
Drs. James Hansen and Jiangbing Zhou of the Yale School of Medicine have confirmed that PAT‐DX1 and PAT‐DX1‐NP target tumor spheres derived from human glioblastoma cancer stem cells (CSCs). Primary glioblastoma stem cells from human tumor explants were grown in culture as tumor spheres. Tumor spheres are recognised as a useful tool for pre‐clinical studies as they retain tumor heterogeneity and more closely represent the original patient tumor. Treatment with PAT‐DX1‐NP showed significantly increased localization to the CSC tumor spheres compared to unconjugated NPs. Importantly, PAT‐DX1‐NP penetrated into the centre of the tumor 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 tumor spheres.
CSCs are tumorigenic (tumor‐forming) cancer cells found within tumours that have the potential to give rise to all cell types found in a particular cancer sample. Typically, CSCs are; isolated from primary human tumors; able to be grown in culture; and able to differentiate into complete tumors when implanted into model systems.
“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 tumor spheres in vitro is another exciting development,” said Dr. James Campbell, Chief Executive Officer and Managing Director of Patrys. “This data strengthens the case for glioblastoma as a development path for the DX1 technology.”
Dr. Campbell continued “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.”
“With a balance sheet strengthened by the recent $4.6 million placement to strategic, institutional and sophisticated investors, and an expanding network of collaborators investigating PAT‐DX1 and PAT‐DX1‐NP in a range of different tumours, we believe that Patrys is well positioned to explore the broad potential of the Deoxymab technology” added Dr. Campbell.