In this partnership, the financial details of which haven'tbeen released, ZoBio will use its proprietary Target Immobilized NMR Screening(TINS) technology to screen its fragment library against targets nominated byCellCentric. Hit-to-lead and lead optimization activities will be furthersupported by ZoBio's biophysical and medicinal chemistry research services.
"Epigenetics is an exciting, yet challenging, field. We feelthat our unique combination of biophysical and biochemical approaches yieldssignificant advantages in developing small-molecule inhibitors of these targetswith optimal drug-like properties," said Dr. Gregg Siegal, chief scientificofficer at ZoBio, in a statement.
According to Dr. Anthony Brown, scientific director atCellCentric, ZoBio's TINS technology offers a "unique opportunity to identifynovel hit matter against our epigenetic drug targets. The interaction withZoBio will allow us to expand the breadth of our hit-finding capabilities andwill accelerate our ongoing drug discovery activities."
Among the strengths that ZoBio brings to the partnership isan array of biophysics services to support fragment-based drug discovery. Theseservices form an integrated pipeline that includes fragment discovery, nuclearmagnetic resonance-based structural biology services and validation andcharacterization by such orthogonal methods as surface plasmon resonance. Thesecapabilities reportedly enhance the ability to discover fragment inhibitors forvariety of targets, including kinases, protein-protein interaction, antiviralsand membrane proteins such as GPCRs and ligand gated ion channels.
Among CellCentric's reported strengths in the relationshipis its skill in targeting epigenetic processes for new treatments for cancerand a network of leading researchers in some 30 labs worldwide. Active programsat CellCentric include inhibitors to histone methyltransferases and epigeneticenzymes that act via ubiquitination. CellCentric says that it has evaluatedmore than 50 unexploited epigenetic targets across multiple target families.
Notably, in 2010, CellCentric licensed a novel epigeneticdiscovery program to Japan's Takeda Pharmaceutical Co. for a program focused oncancer. Under the terms of agreement, CellCentric received an unspecifiedupfront payment from Takeda but also stood to gain from preclinical andclinical milestones, in addition to royalties, with a total deal value of asmuch as $200 million to CellCentric over the course of the agreement.
Although CellCentric is strongly focused on cancer, thecompany notes, "Epigenetics concerns the cellular processes associated withmodification of chromatin that lead to differential gene expression. It helpsexplain why different cells in the body develop to fulfill specializedfunctions, despite containing identical DNA information." In addition to errorsin epigenetic mechanisms causing aberrant cellular behavior that leads to tumorformation, it can also lead to neurodegenerative diseases, metabolic disordersand inflammatory diseases, meaning that the field has importance in multipletherapeutic arenas.
In fact, in 2011, CellCentric joined a group of leadingacademic researchers around the world to investigate epigenetic mechanismsunderlying diabetes, with CellCentric being the sole commercial partner in theconsortium 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'sleading epigenetic mechanistic understanding to other areas associated withepigenetic loss of cell fate control."
For its part, ZoBio has touted a pair of other deals in recentmonths, the most recent of which is a deal inked in January with HeptaresTherapeutics—a collaboration to discover fragment ligands for Heptares'stabilized GPCRs, which it has dubbed StaRs. Under the agreement, ZoBio willfirst develop methods to rapidly extract and immobilize a GPCR targetdesignated by Heptares. Subsequently, ZoBio will apply its proprietary TINStechnology to screen a library of drug fragments for specific binding to thetarget.
Also, in September 2011, ZoBio reached an agreement tosupply a variety of biophysics research services to Abbott in the area of hitmatter discovery and characterization. Among the services to be provided, ZoBiowill use its proprietary TINS technology for ligand discovery on a variety oftargets designated by Abbott. Orthogonal validation will be provided throughZoBio's Biacore instrumentation.