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: Behaviour of adult epithelial stem cells
Epistem’s core science is based on three decades of groundbreaking research led by co-founder Professor Chris Potten at the Paterson Institute for Cancer Research at the Christie Hospital in Manchester, UK. Models developed by Professor Potten identify the exact location of stem cells and track their migration to produce specialised functional cells in the small intestine. These models remain unmatched for elucidating the behaviour of adult (non-embryonic) stem cells in any tissue.

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 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 mechanism of action (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.