X-Chem, Inc., a privately held biotechnology company applying its cutting-edge lead discovery capabilities to the generation of novel small molecule therapeutics, announced a multi-target drug discovery agreement with AbbVie. The collaboration is focused on the discovery and development of novel treatments for diseases in oncology and immunology.

Under the terms of the agreement X-Chem will deploy its DNA-encoded library discovery platform for the identification of novel small-molecule inhibitors of both promising new targets as well as validated targets that have been historically challenging to address. AbbVie has an exclusive option to license active hits and leads generated in the course of the collaboration and is responsible for all further development and commercialization. Financial terms were not disclosed.

“X-Chem’s ongoing improvements to its platform have demonstrated further increases in success in identifying small molecule hits and leads against a broad range of difficult biological targets,” stated Rick Wagner, Ph.D., chief executive officer of X-Chem. “We look forward to applying our advanced drug discovery capabilities in collaboration with the scientists at AbbVie, a leader in the development of drug treatments in oncology and immunology.”

Due to the size and diversity of the DEX library, X-Chem can discover multiple series of novel, potent and selective lead compounds at an unprecedented rate of success against a wide range of targets, including some that previously failed using conventional screening methods. A number of proprietary innovations in library design, screening methodology and bioinformatics underlie the exceptional performance of the DEX platform. In particular, X-Chem’s approach to library construction allows for additional chemical reactions to become useable in DNA-encoded library synthesis. Together, these developments result in a much greater repertoire of diversity for small molecules, which cover a range of categories including fragment molecules, small molecular weight heterocyclic compounds, and macrocyclic structures. This diverse library, combined with a heightened ability to detect active molecules, has yielded a robust process that has been highly successful against targets categorized as difficult or intractable.

The X-Chem drug discovery engine is based on a library, currently in excess of 120 billion compounds and growing, generated by iterative combinatorial synthesis of small molecules tethered to DNA tags that record the synthetic history of the small molecule. Every small molecule in the library has a unique DNA barcode attached it. The library is screened as a mixture using affinity-based binding to a target of interest. Certain rare molecules in the library that bind to the target can be “fished out,” while the rest of the molecules are washed away. DNA sequencing methods are then used to detect molecules that are enriched when bound to the target. The diverse nature of the library produces multiple families or clusters of related molecules that bind to the target, forming a basis for emergent structure-activity relationships. Structure-activity relationships are typically used by medicinal chemists to guide iterative chemical maturation of a molecule into a drug. Based on the synthetic history encoded in the DNA sequence information, molecules are then made without the DNA tag attached, and tested for activity in conventional assays.