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 collaboration with Sanofi. The collaboration is focused on the potential development of several programmes for treatments in therapeutic areas such as oncology, rare diseases, diabetes, among others.

Under the terms of the agreement, X-Chem is applying its discovery engine, which leverages a high diversity, proprietary DNA-encoded small molecule library to seek the identification of novel leads for the Sanofi programs. Sanofi has an exclusive option to license any compounds generated in the course of the collaboration. The financial terms of the agreement were not disclosed.

“X-Chem has specifically built its library and discovery platform to address the challenges a broad range of targets and enable the discovery of multiple chemical series directly out of our primary screens” said Rick Wagner, Ph.D., chief executive officer of X-Chem. “We are delighted to partner with Sanofi to identify lead molecules to difficult, high value therapeutic targets.”

“This alliance, together with our recently announced collaboration and license agreements, further validates the high-value of our platform as well as X-Chem’s flexibility in finding win-win partnership frameworks for each of our collaborators,” said Ed Koval, senior VP of corporate development at X-Chem.

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 design 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 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 to 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 wash 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.