Drug Research
Drug Discovery & Development

X-Chem, Taiho establish multi-target drug discovery collaboration

Published 21 December 2016

X-Chem has entered into a multi-target drug discovery collaboration with Taiho Pharmaceutical.

This collaboration will grant Taiho access to X-Chem’s DEX technology which is based on DNA-encoded libraries of small molecules with more than 120 billion molecules. The aim of the collaboration is to discover innovative lead structures for complex drug targets in multiple therapeutic areas with unmet medical need.

X-Chem CEO Rick Wagner, Ph.D. said: “X-Chem continues to innovate and push the boundaries of its DEX Technology platform.

“The agreement with Taiho reflects our significant and increasing success in delivering drug leads against a broad range of challenging targets. We’re delighted that Taiho will be our first partner in Japan and look forward to fully deploying our productive platform against their internal targets.”

Under the terms of this new agreement, X-Chem will receive an up-front payment as well as potential pre-clinical, clinical and regulatory milestone payments and sales milestones, up to a total of $352m.

Taiho has an exclusive option to license any programs generated in the course of the collaboration. X-Chem will also receive royalties for each successfully commercialized drug that results from a licensed collaboration program.

About the DNA-Encoded X-Chem (DEX) Library and Platform

Due to the size and diversity of the DEXTM 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 DEXTM 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.

About DNA-Encoding

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.

Source: Company Press Release