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LEIDEN, The Netherlands—ZoBio BV and Cambridge, U.K.-based CellCentric have begun working together to discover lead compounds against CellCentric's portfolio of epigenetic therapeutic drug targets.
In this partnership, the financial details of which haven't been released, ZoBio will use its proprietary Target Immobilized NMR Screening (TINS) technology to screen its fragment library against targets nominated by CellCentric. Hit-to-lead and lead optimization activities will be further supported by ZoBio's biophysical and medicinal chemistry research services.
"Epigenetics is an exciting, yet challenging, field. We feel that our unique combination of biophysical and biochemical approaches yields significant advantages in developing small- molecule inhibitors of these targets with optimal drug-like properties," said Dr. Gregg Siegal, chief scientific officer at ZoBio, in a statement.
According to Dr. Anthony Brown, scientific director at CellCentric, ZoBio's TINS technology offers a "unique opportunity to identify novel hit matter against our epigenetic drug targets. The interaction with ZoBio will allow us to expand the breadth of our hit-finding capabilities and will accelerate our ongoing drug discovery activities."
Among the strengths that ZoBio brings to the partnership is an array of biophysics services to support fragment-based drug discovery. These services form an integrated pipeline that includes fragment discovery, nuclear magnetic resonance-based structural biology services and validation and characterization by such orthogonal methods as surface plasmon resonance. These capabilities reportedly enhance the ability to discover fragment inhibitors for variety of targets, including kinases, protein-protein interaction, antivirals and membrane proteins such as GPCRs and ligand gated ion channels.
Among CellCentric's reported strengths in the relationship is its skill in targeting epigenetic processes for new treatments for cancer and a network of leading researchers in some 30 labs worldwide. Active programs at CellCentric include inhibitors to histone methyltransferases and epigenetic enzymes that act via ubiquitination. CellCentric says that it has evaluated more than 50 unexploited epigenetic targets across multiple target families.
Notably, in 2010, CellCentric licensed a novel epigenetic discovery program to Japan's Takeda Pharmaceutical Co. for a program focused on cancer. Under the terms of agreement, CellCentric received an unspecified upfront payment from Takeda but also stood to gain from preclinical and clinical milestones, in addition to royalties, with a total deal value of as much as $200 million to CellCentric over the course of the agreement.
Although CellCentric is strongly focused on cancer, the company notes, "Epigenetics concerns the cellular processes associated with modification of chromatin that lead to differential gene expression. It helps explain why different cells in the body develop to fulfill specialized functions, despite containing identical DNA information." In addition to errors in epigenetic mechanisms causing aberrant cellular behavior that leads to tumor formation, it can also lead to neurodegenerative diseases, metabolic disorders and inflammatory diseases, meaning that the field has importance in multiple therapeutic arenas.
In fact, in 2011, CellCentric joined a group of leading academic researchers around the world to investigate epigenetic mechanisms underlying diabetes, with CellCentric being the sole commercial partner in the consortium that hoped to find new targets for small-molecule therapeutics. Although CellCentric's primary focus is in prostate, breast and colon cancer, it noted that the involvement in the new consortium "expands the company's leading epigenetic mechanistic understanding to other areas associated with epigenetic loss of cell fate control."
For its part, ZoBio has touted a pair of other deals in recent months, the most recent of which is a deal inked in January with Heptares Therapeutics—a collaboration to discover fragment ligands for Heptares' stabilized GPCRs, which it has dubbed StaRs. Under the agreement, ZoBio will first develop methods to rapidly extract and immobilize a GPCR target designated by Heptares. Subsequently, ZoBio will apply its proprietary TINS technology to screen a library of drug fragments for specific binding to the target.
Also, in September 2011, ZoBio reached an agreement to supply a variety of biophysics research services to Abbott in the area of hit matter discovery and characterization. Among the services to be provided, ZoBio will use its proprietary TINS technology for ligand discovery on a variety of targets designated by Abbott. Orthogonal validation will be provided through ZoBio's Biacore instrumentation.