Future technologies for biologics drug discovery
Despite an increasing spend in drug development, many diseases remain unaddressed with little hope of finding new treatment options by conventional means. One reason for this is the lack of knowledge regarding which proteins are druggable, and which pockets on the protein surface might be most beneficially targeted by small molecules.
Current methods for discovering new drug targets rely on genetic knock-out (CRISPR) or knock-down (RNAi) methods. While these techniques can be useful in providing candidate therapeutic target genes, the next step of developing protein-targeting therapies often stalls due to insufficient information on druggability.
To address this problem, PhoreMost has developed a functional proteomics / phenotypic screening technology called “Protein Interference” (PROTEINi®) that yields both the target’s identity as well as information on available druggable sites within the target. PROTEINi utilises proprietary large ( >1 Million), diverse, lenti-encoded libraries of small, self-folding, three-dimensional peptide "shapes", which are expressed in live cells and, much like small molecules, interfere and engage with available pockets on target proteins on a proteome-wide scale. In contrast to shRNA or CRISPR screens, PROTEINi works on the same level as most small molecules (the proteome) and is not influenced by gene copynumber, SNPs or genetic buffering. The process discovers novel targets for a given assay system as well as peptides engaging this target functionally as a starting point for drug discovery.
PhoreMost currently has internal small molecule programs in Oncology, Immuno-Onc and Neurodegenerative disorders. We have recently also expanded the method into Targeted Protein Degradation space to systematically discover novel and functional E3 linkage sites across a set of 600 ligases.