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In Pursuit of Hot Autoimmune Target, GSK and Academics Team Up

Drug targets are like fashion items. When a trendsetter proves one is worth spending money on, a lot of followers pile in. That’s no knock on drug developers, necessarily: When a new target shows some promise, it’s good to have lots of researchers with different ideas and approaches trying to find a drug to hit it. In the last few years, many of those researchers from the academic and industry camps who traditionally wouldn’t work together are joining forces.

Enter drug giant GlaxoSmithKline (NYSE: GSK), which has tried various schemes to make its research groups more biotech-like, including the spin-out of an immunology team into a separate biotech company. That company, Tempero Pharmaceuticals of Cambridge, MA, has teamed up with two academic labs to go after one of the most intriguing targets in immune disease, the IL-17 pathway, and a paper they published recently has caught the eyes of their peers.

First some background about IL-17, short for interleukin 17. Companies such as Novartis, Amgen, and Eli Lilly are developing monoclonal antibodies against IL-17 or related targets to treat psoriasis, rheumatoid arthritis, and other diseases in which the patient’s immune system turns against his or her own body. IL-17 is a small protein that plays key roles in bringing the body’s immune ammunition to bear against invaders. But at times the immune system misfires and produces too much IL-17, driving many autoimmune diseases. IL-17’s main source is a cell, discovered less than a decade ago, called T helper 17 or Th17.

The discovery of Th17, and the attention devoted to it, has opened up potentially a new way to attack IL-17-mediated autoimmune disease: go after the master switches that control Th17’s development. Toggling those switches off would block IL-17 production and possibly a host of other mischievous effects the cell produces, which in turn could lead to therapies effective against multiple autoimmune disorders.

Tempero, which is majority-owned by GSK, and two academic labs teamed up in a series of studies published recently in the journal Immunity to describe how a protein known in shorthand as RORγT (“ROR gamma T”) is critical to Th17’s development. Combining T cell biology, genomic analysis, and massive drug libraries from GSK, the group also found three compounds that could provide a rough model for future treatments for autoimmune diseases.

By targeting RORγT instead of targeting IL-17 directly, these small molecules “blocked the ability of Th17 to create IL-17,” said Alex Marson of the University of California, San Francisco, a coauthor of the Immunity paper. “We also found they improved outcomes in a mouse model of multiple sclerosis. They are blocking the pathogenic function of Th17 cells.”

Marson’s lab collaborated with Vijay Kuchroo of Harvard Medical School and scientists at Tempero, which Kuchroo helped found in 2009. The study caught the eye of Daniel Cua of Merck Research Laboratories in Palo Alto, CA, whose work helped bring Th17 cells to light. In an accompanying review in Immunity, Cua and his Merck colleague Jacob Lee lauded the study’s reach and “potential clinical value.”

“What distinguishes this study from others is the combined use of a large-scale pharmaceutical discovery platform with innovative genome-side analysis of RORγt target genes in Th17 cells,” wrote Cua and Lee.

That’s a recipe an academic-only group would be hard-pressed to follow, and it’s a measure of … Next Page »

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