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

5/12/14Follow @alexlash

(Page 2 of 2)

how far the industry and academic sides, once philosophically isolated, have come together in recent years. Academia needs new sources of funding, with National Institutes of Health funding subject to sequestration-era budget cuts. And pharma, making research cuts of its own, needs to find new sources of innovation.

The next step, meanwhile, is to take the compounds that showed promise in mice and refine them via the long process of medicinal chemistry. Being first into the clinic isn’t necessarily the goal, said Tempero principal scientist Jianfei Yang. “Lots of Big Pharma are in this field, but being first in human doesn’t mean your compound will be approved by FDA,” Yang told Xconomy. “You need a high quality compound.”

Whitehouse Station, NJ-based Merck’s (NYSE: MRK) agreement last year with Plymouth, MI-based Lycera is one example of recent dealmaking around RORγT. Amgen’s (NASDAQ: AMGN) tie-up with Japanese firm Teijin is another.

There are other industry collaborations, but Tempero’s work to date remains solely in GSK’s hands. As Xconomy first reported in 2009, the firm was spun out of GSK’s Immuno-Inflammation Centre of Excellence in Drug Discovery, or CEDD, to house the group’s regulatory T cell team and recruited Kuchroo and two other academic founders to contribute their T cell expertise. “In order to attract the academic experts, and build a group quickly, the decision was made that this was a ripe opportunity to set this up as an independent company with a biotech model,” former CEO Spiros Jamas explained to Xconomy in 2010. (Jamas left in 2012.)

Tempero also recruited independent directors John Maraganore, CEO of Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ: ALNY), and Rich Aldrich, both mainstays of the Boston biotech scene. Although both have venture ties—Maraganore is now a venture partner at Third Rock, and Aldrich runs the Longwood Fund—Tempero has no outside backers.

The academic research that fed into Tempero has, of course, received funding from a number of sources, including the National Multiple Sclerosis Society, which funded some of the work in Kuchroo’s lab that has elucidated Th17 biology. “I’m excited there’s a possibility here for multiple sclerosis, but it’s broader than just MS,” said National Multiple Sclerosis Society chief research officer Tim Coetzee. “There are implications for a range of autoimmune diseases.”

That’s because the three compounds that the Marson-Kuchoo-Tempero team identified are not only blocking Th17 cells from producing IL-17, but they are also preventing “naïve” T cells that haven’t yet differentiated from turning into Th17 cells. It’s both a short-term and long-term fix, said Yang. “If the drug only blocks the differentiation of Th17, that takes a long time to get efficacy. But if you could block Th17 cytokine production, you could see [faster] efficacy, then [also have] long term blocking of differentiation.”

Much work remains to be done to prove that targeting RORγT is a viable—and safe—approach in humans. RORγT is a transcription factor; that is, it binds to a cell’s DNA and controls its gene expression. One curiosity Marson noted and Cua highlighted in his review was that two of the three IL-17-blocking compounds seemed to cause RORγT to bind to new sites in the Th17′s DNA. That could be a hint that such compounds could unintentionally trigger the production of proteins that make a patient worse, not better. Is it merely a curiosity, or is a potential safety problem? That’s a question to be answered in further studies, along with many, many others.

Alex Lash is Xconomy's National Biotech Editor. He is based in San Francisco. Follow @alexlash

Single Page Currently on Page: 1 2 previous page

By posting a comment, you agree to our terms and conditions.