New class is in session

LONDON—GlaxoSmithKline PLC (GSK) and Yale Universityrecently established a drug discovery research collaboration to design apotential new class of medicines that could degrade disease-causingproteins.

The idea is to combine GSK's expertise in medicinalchemistry with Yale's work on proteolysis targeting chimeric molecules(PROTACs). According to GSK, PROTAC technology guides disease-causing proteinsto a cell's "garbage disposal" where they can be destroyed. Mutant orhigher-than-normal amounts of these proteins typically drive diseaseprogression 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, enzymesmake great drug targets, but they only make up about 20 percent of the entireproteome of humans," Dr. Craig M. Crews, executive director of Yale Center forMolecular Discovery, tells ddn. "So, a significant part of the proteomecurrently isn't addressable using a small-molecule approach, and the questionis how to make this non-drugable part of the proteome pharmaceuticallyvulnerable."

RNAi entered onto the scene with a lot of promise, Crewsadds, but the challenges of making RNAi therapies work in humans are many.

"Companies like GSK are beginning to explore alternativeapproaches to go after these targets," says Crews, who is also a Lewis B.Cullman Professor of Molecular, Cellular and Developmental Biology and aprofessor of chemistry and pharmacology at Yale, and is spearheading the Yaleside of the collaboration with GSK.

Under the agreement, a joint research team will work to showthat PROTACs can be turned into future medicines. GSK will then have the rightto use this technology for multiple disease-causing proteins across all therapyareas. For each protein-degrading drug that is discovered and developed, Yalewill be eligible for milestone and royalty payments. Several collaborationsbetween GSK and U.K.-based universities have been announced recently that alsoinvolve jointly working toward common milestones and include an element ofrisk-sharing by both parties.

This partnership, however, differs both because of its scopearound a potential new class of medicines and because it is the first suchcollaboration between GSK and a U.S.-based academic center.

"With consolidation in the industry, internal research hasbeen hurt at many companies, and so they are reevaluating the potential foracademic outreach and collaborations with academia," Crews notes. "The YaleCenter for Molecular Discovery is where Yale's basic science is reduced topractice, if you will, for the purpose of making reagents, for example, butalso looking for commercialization opportunities. I've seen in the last fewyears a growing interest in companies' willingness to work with academia andhigher interest in setting up industry-academia collaborations, and one of thethings I'm doing in addition to the research side of the GSK collaboration isto 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 butunproven therapeutic approaches to jump from the academic lab more quickly intothe early-stage pharmaceutical pipeline," said Kris Famm, head of GSK's ProteinDegradation effort, who will lead the program along with Crews, in the newsrelease about the deal. "The groundbreaking work Craig and his team have donemay allow us to tackle a whole host of disease-causing proteins that werepreviously out of reach for medicines, and it is exciting to work together totry to realize that promise."

Scientifically, Crews had already taken the PROTACtechnology up through proof of concept, and that entailed a peptide-basedapproach, he says.

"More recently, I have been focusing on small-molecule-basedversions of that initial proof of concept," he explains. "So, as I am makingthese molecules, the driving force is to make them more drug-like. From mypoint of view, teaming up with a company like GSK with many decades of makingsuccessful drugs is a good situation for us. Not only do we get a partner whohas experience with this but we also have a path forward for taking it to theclinic if we're successful."

The collaborative work with GSK and Yale is alreadyunderway, with the goal of showing proof of principle for the technology by theend of this year.

GSK acquires Cellzome for $99 million

LONDON—GlaxoSmithKline PLC (GSK) announced in May 15 theestablishment of an agreement by which it will acquire those shares it does notalready own in proteomics technology company Cellzome. GSK will acquire theshares for $99 million, and Cellzome will become part of GSK's research anddevelopment organization.

GSK currently owns a 19.98 percent equity interest inCellzome, and after the acquisition, it will assume full control of thecompany. In conjunction with the acquisition, Cellzome shareholders, with GSKincluded, plan on creating a spinoff company. The spin-off would hold therights to those of Cellzome's assets and activities that GSK does not want tofurther develop.

"The acquisition of Cellzome adds significantly to ourscientific capabilities and capacity to characterize drug targets and providesthe opportunity to further enhance GSK's ability to bring medicines to patientsin 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. Formore on this acquisition at the ddn website, click here.