Discovery Platform

Therapeutics strategy
Epistem is discovering the key regulators of adult epithelial stem cells to control cell production in the therapeutic areas of oncology and epithelial diseases. The Company will develop protein therapeutics based on the body's regulators of stem cells and identify novel targets/pathways for intervention with antibodies and small molecules.
 
Core biology
Epistem's discovery platform identifies novel targets and leads for tissue regeneration, oncology and GI diseases.  The platform is underpinned by our expertise in epithelial stem cell biology and focuses on discovering and elucidating the body's key soluble regulators of cell production.  We apply high-resolution tissue profiling (mRNA and protein) for candidate identification and to establish mechansim of action (MOA) linkages between in vitro and in vivo data.  We have benchmarked with controls and have generated four novel hits.

We are now considering disease-specific partnerships with pharmaceutical companies, to advance our hits and to identify novel targets for the development of biotherapeutics.

High-resolution gene expression profiling
Epistem scientists have comprehensively profiled gene expression patterns in the small intestine and a range of other epithelial tissues to identify the regulators of proliferation, differentiation, apoptosis, and self-renewal. We have focused primarily on the damage response process of apoptosis, tissue repair, and re-establishing steady state in murine intestinal tissues following radiation/chemotherapy.

Epistem scientists have selected a group of over 250 genes from which to identify candidate soluble stem cell regulators. The genes were selected from mRNA expression profiling and proteomic analyses at specific phases of the damage response pathway. Production, purification, and characterisation of the recombinant proteins is underway.

In vivo stem cell activity assays
The Company is evaluating the activity of the recombinant proteins in its industry standard in vivo intestinal stem cell function assays. Proteins are administered prior to inducing damage by radiation, and intestinal stem cell activity is determined by a quantitative readout of protection and/or accelerated recovery that is benchmarked against keratinocyte growth factor (KGF).

Proteins that demonstrate robust and reproducible activity undergo further characterisation in non-radiation models to elucidate the in vivo biological  MOA. These studies identify the target cells (i.e., stem cells or transit amplifying progenitor cells) and a protein's subsequent impact on intestinal cell production.