“We had this novel idea that we could use bio-orthogonal linker chemistry to deliver self assembling inhibitors with a greater binding footprint for ‘undruggable’ targets inside the cell and it’s great to work with Coferon to turn those ideas into action”
- Dr. Francis Barany & Dr. Maneesh Pingle (Weill-Cornell Medical College) and Dr. Don Bergstrom (Purdue University), Coferon’s academic founders.
Coferon’s approach bridges the gap between small molecule drugs – which can be orally delivered and hit targets both in and outside the cell but usually lack sufficient binding footprint to be highly specific – and large biomolecule drugs (like antibodies) which can generate exquisite target specificity but cannot either be delivered orally or access targets inside the cell. The proprietary reversible, covalent linker chemistries we have developed allow carefully designed monomeric components (comprised of pharmacophores, connectors and one-half of a proprietary summa linker pair) to be administered as a single drug product in the form of covalently linked dimers designed for optimal binding to the target protein. Following administration, the dimers dissociate into monomers under physiological conditions.
The monomers can then distribute throughout the body, accessing target tissues and entering target cells before reassembling as a tightly bound dimer using the target protein itself as a template for preferential self-assembly. These Coferon dimers are typically twice the size of most orally bioavailable small molecules and are, as such, able to impart significantly more potent and selective binding interactions on their target. We have been able to demonstrate initial proof-of-concept for the coferon approach - in both in vitro and in vivo settings – for both heterodimeric and homodimeric manifestations of the technology using human mast cell ß-tryptase as a model target (see Coferon Toolbox figure above). Coferon has exclusively licensed the foundation patent filing from Cornell and Purdue Universities and has built a comprehensive network of patent filings that anchor this unique technology platform.
We are now applying the technology against an anti-infectives target and in a comprehensive program targeting intracellular epigenetic regulatory proteins and their Protein Interaction Domains (PIDs). Therapeutics targeting the BRD family, most notably BRD4, are being actively pursued by many companies with classic small molecule approaches. The BRD4, BRD2, BRD-T and the BRD-NUT oncogenic fusion protein all offer intriguing targets for therapeutic intervention and are an initial focus of the Coferon epigenetic discovery program.