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X-Chem, Navitor Pharma ink licensing pact on small molecules targeting mTORC1 activation
Waltham, Massachusetts | Thursday, April 2, 2015, 10:00 Hrs  [IST]

X-Chem, Inc., a privately held biotechnology company, announced that Navitor Pharmaceuticals, Inc., a biopharmaceutical company developing novel medicines by targeting cellular nutrient signaling, exercised its option to obtain an exclusive license to a series of small molecules targeting the activation of mTORC1, a key protein complex that orchestrates nutrient-mediated cellular metabolism and growth.

The compounds licensed by Navitor were discovered by X-Chem screening their proprietary DEX platform against protein targets supplied by Navitor under a drug discovery agreement established by the parties in 2014. X-Chem received research funding from Navitor upon initiation of the agreement and a license fee upon exercise of the license. X-Chem is also eligible for additional consideration upon achievement of further milestones. Financial details were not disclosed.

“X-Chem has impressed us by succeeding in rapidly discovering novel and selective modulators for an unprecedented and challenging cellular pathway being studied at Navitor,” said George P. Vlasuk, Ph.D., president and chief executive officer of Navitor. “We are excited to bring these promising compounds in-house and pursue their preclinical development in parallel with our other proprietary drug discovery programmes selectively targeting the mTORC1 nutrient signaling pathway.”

“X-Chem partners with emerging biotechnology companies to enable innovative therapeutics in promising new areas of biological research,” said Rick Wagner, Ph.D., president and chief executive officer of X-Chem. “By combining Navitor’s unique biological expertise in cellular nutrient signaling with X-Chem’s powerful DEX platform, we are helping rapidly translate Navitor’s breakthrough biological insights into innovative therapeutics.”

“Over the past several years, X-Chem has discovered and licensed multiple small molecule drug discovery programs to leading pharmaceutical companies under on-going partnerships”, said Diala Ezzeddine, Ph.D., EVP and chief business officer of X-Chem. “The collaboration with Navitor represents a new type of partnership adapted to the specific business needs of early-stage biotechnology companies.”

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 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.

X-Chem, Inc. is a biotechnology company based in Waltham, Massachusetts. The company’s mission is to apply its powerful product engine to the discovery of small molecule compounds against high-value therapeutic targets.

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