New class is in session
June 2012
by Jeffrey Bouley  |  Email the author


LONDON—GlaxoSmithKline PLC (GSK) and Yale University recently established a drug discovery research collaboration to design a potential new class of medicines that could degrade disease-causing proteins.   
The idea is to combine GSK's expertise in medicinal chemistry with Yale's work on proteolysis targeting chimeric molecules (PROTACs). According to GSK, PROTAC technology guides disease-causing proteins to a cell's "garbage disposal" where they can be destroyed. Mutant or higher-than-normal amounts of these proteins typically drive disease progression in areas such as oncology, inflammation and infections, GSK notes, but many cannot be tackled by traditional ways of making drugs.  
"If you think about screening and drug discovery, enzymes make great drug targets, but they only make up about 20 percent of the entire proteome of humans," Dr. Craig M. Crews, executive director of Yale Center for Molecular Discovery, tells ddn. "So, a significant part of the proteome currently isn't addressable using a small-molecule approach, and the question is how to make this non-drugable part of the proteome pharmaceutically vulnerable."  
RNAi entered onto the scene with a lot of promise, Crews adds, but the challenges of making RNAi therapies work in humans are many.  
"Companies like GSK are beginning to explore alternative approaches to go after these targets," says Crews, who is also a Lewis B. Cullman Professor of Molecular, Cellular and Developmental Biology and a professor of chemistry and pharmacology at Yale, and is spearheading the Yale side of the collaboration with GSK.  
Under the agreement, a joint research team will work to show that PROTACs can be turned into future medicines. GSK will then have the right to use this technology for multiple disease-causing proteins across all therapy areas. For each protein-degrading drug that is discovered and developed, Yale will be eligible for milestone and royalty payments. Several collaborations between GSK and U.K.-based universities have been announced recently that also involve jointly working toward common milestones and include an element of risk-sharing by both parties.   
This partnership, however, differs both because of its scope around a potential new class of medicines and because it is the first such collaboration between GSK and a U.S.-based academic center.  
"With consolidation in the industry, internal research has been hurt at many companies, and so they are reevaluating the potential for academic outreach and collaborations with academia," Crews notes. "The Yale Center for Molecular Discovery is where Yale's basic science is reduced to practice, if you will, for the purpose of making reagents, for example, but also looking for commercialization opportunities. I've seen in the last few years a growing interest in companies' willingness to work with academia and higher interest in setting up industry-academia collaborations, and one of the things I'm doing in addition to the research side of the GSK collaboration is to reach out to other researchers in the United States. This is the first U.S. deal like this that GSK has done, but they would like to do more."
"This partnership is exploring a new way for promising but unproven therapeutic approaches to jump from the academic lab more quickly into the early-stage pharmaceutical pipeline," said Kris Famm, head of GSK's Protein Degradation effort, who will lead the program along with Crews, in the news release about the deal. "The groundbreaking work Craig and his team have done may allow us to tackle a whole host of disease-causing proteins that were previously out of reach for medicines, and it is exciting to work together to try to realize that promise. "  
Scientifically, Crews had already taken the PROTAC technology up through proof of concept, and that entailed a peptide-based approach, he says.  
"More recently, I have been focusing on small- molecule-based versions of that initial proof of concept," he explains. "So, as I am making these molecules, the driving force is to make them more drug-like. From my point of view, teaming up with a company like GSK with many decades of making successful drugs is a good situation for us. Not only do we get a partner who has experience with this but we also have a path forward for taking it to the clinic if we're successful."  
The collaborative work with GSK and Yale is already underway, with the goal of showing proof of principle for the technology by the end of this year.  

GSK acquires Cellzome for $99 million  
LONDON—GlaxoSmithKline PLC (GSK) announced in May 15 the establishment of an agreement by which it will acquire those shares it does not already own in proteomics technology company Cellzome. GSK will acquire the shares for $99 million, and Cellzome will become part of GSK's research and development organization.   
GSK currently owns a 19.98 percent equity interest in Cellzome, and after the acquisition, it will assume full control of the company. In conjunction with the acquisition, Cellzome shareholders, with GSK included, plan on creating a spinoff company. The spin-off would hold the rights to those of Cellzome's assets and activities that GSK does not want to further develop.  
"The acquisition of Cellzome adds significantly to our scientific capabilities and capacity to characterize drug targets and provides the opportunity to further enhance GSK's ability to bring medicines to patients in a more effective manner," John Baldoni, senior vice president of Platform & Technology Science at GSK, said in a press release.  
The acquisition is not subject to third party approvals. For more on this acquisition at the ddn website, click here.  

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