X-Chem, Inc., a biotechnology company focused on the generation of novel small molecule therapeutics using its proprietary DNA-encoded library platform, has initiated a drug discovery collaboration with Alexion, a global leader in the development and commercialization of life-transforming therapies for patients with severe and ultra-rare disorders.
“This agreement with X-Chem is an important element of Alexion’s strategy for addressing targets and developing first-in-class therapeutics for patients with life-threatening and ultra-rare disorders”
X-Chem will deploy its proprietary drug discovery engine, which is based on an ultra-large, high-diversity library in excess of 100 billion molecules, to identify novel drug candidates against targets chosen by Alexion. Under the terms of the agreement Alexion will have the exclusive worldwide rights to develop and commercialize novel compounds arising from the collaboration. X-Chem will receive an upfront payment and would receive additional payments upon the achievement of specified research, development and regulatory milestones. In addition, X-Chem would receive royalty payments on the sale of products resulting from the collaboration.
“This agreement with X-Chem is an important element of Alexion’s strategy for addressing targets and developing first-in-class therapeutics for patients with life-threatening and ultra-rare disorders,” said Martin Mackay, executive vice president and head of global R&D at Alexion. “We are very pleased to collaborate with X-Chem and gain access to their innovative platform.”
“X-Chem is excited to collaborate with Alexion, a leader in the treatment of patients with severe, rare diseases," said Richard W. Wagner, CEO of X-Chem. "This collaboration will enable Alexion to leverage the power of X-Chem’s discovery engine for pursuing challenging targets of clinical importance.”
Due to the size and diversity of the 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 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 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 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.