Assistant Managing Editor

How does a big pharma firm ensure that early stage research in the hot area of autoimmune diseases doesn't get lost amid expanding late-stage pipelines?

London-based GlaxoSmithKline plc answered that question by forming 2009 start-up Tempero Pharmaceuticals Inc. to carry forth a business plan that first emerged from GSK's Immune-Inflammation Center of Excellence in Drug Discovery focusing on Th17 and Treg biology. At the time, GSK "realized it would take a fairly early stage research effort" to build a target discovery platform and capture intellectual property on novel targets and compound, said Tempero CEO Spiros Jamas.

But it's not a spinout in the traditional sense. "There's not a word yet to define Tempero," Jamas told BioWorld Today. "A spinout is normally a company divesting an asset or technology. This wasn't a divestment. GSK has a strategic interest in [the technology]."

Like its big pharma brethren, GSK has been increasingly turning to biotech – or to the biotech model – to handle the early stage discovery and development work. In fact, GSK's strategy has included breaking up its drug discovery work into smaller performance units designed to operate like a more productive, cost-efficient biotech. "Tempero is taking that model one step further," Jamas said, "setting it up as an independent company from scratch."

The "real linchpin" in the company are the three academic founders – Diane Mathis, Christophe Benoist and Vijay Kuchroo – as the scientific founders, he added.

Still, Cambridge, Mass.-based Tempero's link to GSK remains strong. The pharma firm retains the right to buy Tempero after certain milestones have been reached.

GSK also was the sole investor in the start-up's Series A round and is a majority shareholder. The amount of that initial round was not disclosed, though Jamas called it "more typical of a significant Series A or Series B round," and said the funding should take the company through 2012. "It allows us to develop candidates close to Phase I," he added, as well as to build out the firm's intellectual property, which is "another important factor for securing that next round of money."

Tempero, so named for the Latin word meaning "balance" and "harmony," is working on a relatively new T-cell lineage that's been found to play a role in both inflammation and tissue damage. T-helper 17 (Th17) cells are responsible for producing a number of cytokines and has become an important area of interest in the autoimmune space, and a number of firms are at work developing antibodies targeting interleukin-17, a cytokine produced by Th17 cells that is associated with tissue damage and chronic inflammation, Jamas said.

Among those include Basel, Switzerland-based Novartis AG, which has an IL-17-targeted antibody that has demonstrated encouraging activity in psoriasis and uveitis.

But Th17 cells "also make a number of other inflammatory cytokines," Jamas said. Blocking a single cytokine has proved effective, but Tempero is hoping that blocking more than one will produce an even more robust effect. The firm has a small-molecule program at the lead optimization stage that would be "a more effective way of shutting down pathogenic Th17 cells," by going after the target to shut down multiple cytokines, as well as to prevent naive T cells from differentiating into Th17 effector cells in the first place, he said.

Potential indications for Tempero include psoriasis, inflammatory bowel disease, rheumatoid arthritis and lupus. "But our key goal in early human proof-of-mechanism studies is to prove that our compounds can affect the target in human diseases." Jamas said. "Then we'll let the biology lead us to the right indication."

Also in early development is a program focused on Tregs (regulatory T cells). There are a number of different types of Tregs that are key to controlling inflammation in the gut or in fat tissue. Tempero is working to figure out pathways to control Treg development, which could open the door to a range of immune-inflammatory disorders.

Over the next two years, Tempero plans to advance two development candidates into Phase I and add more early screening targets to its pipeline.

Going forward, the biotech will be able to take advantage of GSK's drug discovery capabilities, but it also has the right to seek external funding in future financing rounds.

"It will be up to Tempero's board to determine the best funding strategy," Jamas said.

Tempero currently has about 17 employees, but is expected to grow. Jamas predicted the firm's staff will be in the "mid-20s" by the end of this year.