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What was old is new again
January 2013
by Jim Cirigliano  |  Email the author
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BASEL, Switzerland—A multiyear collaboration between Swiss pharmaceutical giant Roche and the Broad Institute of MIT and Harvard will investigate a diverse collection of more than 300 terminated clinical-stage compounds.  
 
"Over the last 20 years of drug discovery, we have created many drug candidates that did not make it to market," Roche's head of medicinal chemistry, Karen Lackey, said in a statement announcing the collaboration. "By compiling these compounds into an annotated set and collaborating with the Broad Institute … we hope to discover ways to repurpose these compounds that will be beneficial for patients."  
 
Roche's collection of terminated clinical compounds is called the Roche Repurposing Compound Collection (RRCC). The collection includes more than 300 compounds that failed to meet critical Phase II milestones for their intended targets, or that were halted for strategic reasons. The compounds were originally geared toward a wide variety of conditions in cardiology, neuroscience, metabolism, virology, oncology and other areas. The Broad Institute will screen the collection using its modern chemical biology approaches, advanced technology platforms and disease expertise to attempt to identify novel indications for these otherwise decommissioned compounds.  
 
The Broad Institute's researchers, led by Dr. Brian Hubbard, director of the Therapeutics Discovery and Development Platform, will employ two primary methods of reexamination to evaluate the compounds for potential novel indications. First, they will screen the entire RRCC, using modern technologies to analyze gene regulation or expression with the goal of linking these compounds to any among a broad spectrum of known biochemical pathways across many disease areas. Second, the Broad Institute will implement novel methods developed in-house to rapidly assess anticancer applications of these compounds to genetically annotated cancer cell lines.
 
Because the initial development of many of these compounds predated the enormous recent strides in modern genomics, most have never been analyzed for their effects on gene expression or compared against genetically annotated disease cell lines.   Researchers will be looking for interesting observations or findings that they hope will lead them to identify novel targets for the terminated compounds. Discovering disease associations will help to predict which of these compounds are most likely to show success in new clinical evaluations. Although admittedly unlikely, Lackey says it could even be possible to identify a direct repurposing opportunity for an existing compound.
 
"It's an exceptional experiment," says Hubbard. "I'm not aware of any instances of a company assembling such a unique compound collection and a research institution assessing it across a broad number of areas."  
 
Initially, the collaborators will be working under a flexible "stage 1" of the agreement, in which researchers will screen all compounds in all platforms without preconceiving what they are likely to find. This open-minded approach may identify promising, yet-unknown disease associations. A more in-depth "stage 2" analysis based on these would attempt to connect these results to a relevant patient population.
 
If the reevaluation of the RRCC uncovers favorable indications that promise dramatic benefits to patients, the parties would negotiate in good faith the terms of furthering drug development.  
 
"If we can identify any patient population that can benefit from existing technology that Roche has developed, that's a success," says Hubbard.
 
"It's important to note that this is not an exclusive agreement, but a concept," says Lackey. "We're open to other groups coming in with other platforms, and would be open-minded to any proposals, especially if they're focused on a patient population."
 
Financial terms of the agreement were not disclosed.  
 
Roche is one of the largest pharmaceutical companies in the world, with more than 80,000 employees and $47.8 billion in sales in 2011. Its diverse biotech portfolio includes medicines in oncology, virology, inflammation, metabolism and CNS.  
 
The Eli and Edythe L. Broad Institute of MIT and Harvard was founded in 2003 to empower this generation of scientists to transform medicine with genome-based knowledge. It maintains collaborative efforts with more than 100 private and public institutions in 40 countries.
 

 
Roche, IMI launch academic-industry stem cell initiative  
 
BASEL, Switzerland—Roche also announced in December that along with the Innovative Medicines Initiative (IMI), it has launched StemBANCC, a new academic–industry partnership that unites 10 pharmaceutical companies and 23 academic institutions.
 
Initiated and coordinated by Roche and managed by Oxford University, StemBANCC aims to use human induced pluripotent stem cells as research tools for drug discovery with the goal of using the technology to develop human disease models and enhance drug development.
 
StemBANCC will focus on peripheral nervous system disorders, central nervous system disorders, neurodysfunctional diseases and diabetes. The project will also investigate the use of human induced pluripotent stem cells for identifying drug targets and biomarkers, screening potential drug treatments and toxicology testing.
 
"The aim of StemBANCC is to generate and characterize 1,500 high-quality human induced pluripotent stem cell lines derived from 500 patients that can be used by researchers to study a range of diseases, including diabetes and dementia," stated Martin Graf, head of the stem cell platform and coordinator of the project at Roche. "The cell lines will help implement patient models that will facilitate the drug development process thanks to the possibility of reproducing the disease mechanism in vitro."
 
Code: E011322

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