The new agreement focuses on the synthesis and delivery of custom libraries to AstraZeneca as well as the transfer of the DEX platform, allowing for in-house screening of DNA-encoded libraries at AstraZeneca.
It is the third agreement between AstraZeneca and X-Chem since 2012 and builds on the success of the parties’ existing collaboration, which has resulted in numerous licenses to novel small molecules across multiple discovery programmes and therapeutic indications to date.
“The DEX platform is an important pillar of our small molecule discovery strategy. This extended collaboration reflects the strength and success of our work with X-Chem in the past five years and secures long-term access to this capability,” said Dr Menelas Pangalos, Executive VP of AstraZeneca’s Innovative Medicines and Early Development Biotech Unit.
“The relationship with AstraZeneca has been one of X-Chem’s longest and most fruitful collaborations,” said Dr Rick Wagner, CEO of X-Chem.
“AstraZeneca’s decision to internalise the DEX platform and conduct DEL screening in-house is a testament to the power of the DEX technology and its importance for small molecule drug discovery in the future.”
Under the terms of the agreement, X-Chem will receive upfront technology access and license fees, as well as multi-year committed funding. X-Chem is also eligible for additional payments linked to the exercise of specific technology transfer options and the achievement of certain R&D and commercial milestones.
In addition, X-Chem will receive royalties for each successfully commercialised drug that results from joint target-based collaboration programmes.
X-Chem’s DEX drug discovery engine is based on a collection of DNA-encoded libraries comprising more than 120 billion unique small molecules derived from iterative combinatorial chemistry processes, where the identity of each compound is recorded in a linked DNA barcode.
The pooled libraries are used in low volume, affinity-based screening against biological targets, whereby ligands are ‘fished out’ and identified via DNA sequencing. Innovations in library design, screening methodologies, and bioinformatics underlie the exceptional performance of the DEX platform.
The use of previously inaccessible chemical reactions and atom-efficient synthesis schemes generate maximal diversity and rule-of-five compliance.
Parallel screens, either varying target concentration or including off-targets, mutants or known ligand competitors, allow for insight into the potency, mechanism of action and specificity of putative hits.
Proprietary statistical and bioinformatics tools identify multiple clusters of related molecules with emergent structure-activity relationships.
These innovations underpin X-Chem’s success against difficult and intractable targets that have failed in conventional screening, generating more than 100 fragment, low molecular weight heterocycle, macrocycle, and irreversible covalent electrophilic lead series that have been licensed by X-Chem’s partners.