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BASEL, Switzerland—A multiyear collaboration between Swisspharmaceutical giant Roche and the Broad Institute of MIT and Harvard willinvestigate a diverse collection of more than 300 terminated clinical-stagecompounds.
 
 
"Over the last 20 years of drug discovery, we have createdmany drug candidates that did not make it to market," Roche's head of medicinalchemistry, Karen Lackey, said in a statement announcing the collaboration. "Bycompiling these compounds into an annotated set and collaborating with theBroad Institute … we hope to discover ways to repurpose these compounds thatwill be beneficial for patients."
 
 
Roche's collection of terminated clinical compounds iscalled the Roche Repurposing Compound Collection (RRCC). The collectionincludes more than 300 compounds that failed to meet critical Phase IImilestones for their intended targets, or that were halted for strategicreasons. The compounds were originally geared toward a wide variety ofconditions in cardiology, neuroscience, metabolism, virology, oncology andother areas.
The Broad Institute will screen the collection using itsmodern chemical biology approaches, advanced technology platforms and diseaseexpertise to attempt to identify novel indications for these otherwisedecommissioned compounds.
 
 
The Broad Institute's researchers, led by Dr. Brian Hubbard,director of the Therapeutics Discovery and Development Platform, will employtwo primary methods of reexamination to evaluate the compounds for potentialnovel indications. First, they will screen the entire RRCC, using moderntechnologies to analyze gene regulation or expression with the goal of linkingthese compounds to any among a broad spectrum of known biochemical pathwaysacross many disease areas. Second, the Broad Institute will implement novelmethods developed in-house to rapidly assess anticancer applications of thesecompounds to genetically annotated cancer cell lines.
 
Because the initial development of many of these compoundspredated the enormous recent strides in modern genomics, most have never beenanalyzed for their effects on gene expression or compared against geneticallyannotated disease cell lines.
 
Researchers will be looking for interesting observations orfindings that they hope will lead them to identify novel targets for theterminated compounds. Discovering disease associations will help to predictwhich of these compounds are most likely to show success in new clinicalevaluations. Although admittedly unlikely, Lackey says it could even bepossible to identify a direct repurposing opportunity for an existing compound.
 
"It's an exceptional experiment," says Hubbard. "I'm notaware of any instances of a company assembling such a unique compoundcollection and a research institution assessing it across a broad number ofareas."
 
 
Initially, the collaborators will be working under aflexible "stage 1" of the agreement, in which researchers will screen allcompounds in all platforms without preconceiving what they are likely to find.This open-minded approach may identify promising, yet-unknown diseaseassociations. A more in-depth "stage 2" analysis based on these would attemptto connect these results to a relevant patient population.
 
If the reevaluation of the RRCC uncovers favorableindications that promise dramatic benefits to patients, the parties wouldnegotiate in good faith the terms of furthering drug development.
 
 
"If we can identify any patient population that can benefitfrom existing technology that Roche has developed, that's a success," saysHubbard.
 
"It's important to note that this is not an exclusiveagreement, but a concept," says Lackey. "We're open to other groups coming inwith other platforms, and would be open-minded to any proposals, especially ifthey're focused on a patient population."
 
Financial terms of the agreement were not disclosed.
 
 
Roche is one of the largest pharmaceutical companies in theworld, with more than 80,000 employees and $47.8 billion in sales in 2011. Itsdiverse biotech portfolio includes medicines in oncology, virology,inflammation, metabolism and CNS.
 
 
The Eli and Edythe L. Broad Institute of MIT and Harvard wasfounded in 2003 to empower this generation of scientists to transform medicinewith genome-based knowledge. It maintains collaborative efforts with more than100 private and public institutions in 40 countries.
 

 
Roche, IMI launch academic-industry stem cell initiative
 
 
BASEL, Switzerland—Roche also announced in December thatalong with the Innovative Medicines Initiative (IMI), it has launchedStemBANCC, a new academic–industry partnership that unites 10 pharmaceuticalcompanies and 23 academic institutions.
 
Initiated and coordinated by Roche and managed by OxfordUniversity, StemBANCC aims to use human induced pluripotent stem cells asresearch tools for drug discovery with the goal of using the technology todevelop human disease models and enhance drug development.
 
StemBANCC will focus on peripheral nervous system disorders,central nervous system disorders, neurodysfunctional diseases and diabetes. Theproject will also investigate the use of human induced pluripotent stem cellsfor identifying drug targets and biomarkers, screening potential drugtreatments and toxicology testing.
 
"The aim of StemBANCC is to generate and characterize 1,500high-quality human induced pluripotent stem cell lines derived from 500patients that can be used by researchers to study a range of diseases,including diabetes and dementia," stated Martin Graf, head of the stem cellplatform and coordinator of the project at Roche. "The cell lines will helpimplement patient models that will facilitate the drug development processthanks to the possibility of reproducing the disease mechanism in vitro."

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