Nuon Therapeutics: A transplanted company tries to teach an old drug new tricks

At a first glance, San Francisco’s Nuon Therapeutics looks like any other specialty-pharmaceutical company that aims to pick up cast-off or failed drugs and try to squeeze some new life out of them. That sort of business model is frequently dull as dishwater, however lucrative it may turn out to be for the investors involved.

Unlike many specialty pharmas, however, Nuon — a recently renamed biotech transplant from Australia that just raised $5 million in a first round of funding — may actually have something scientifically interesting going on. The company, founded in 2002 as Angiogen Pharmaceuticals, does aims to find new uses for marketed drugs. But its first candidate, an old drug called tranilast that Nuon hopes to develop as a new kind of treatment for autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, has a fascinating history that serves to illustrate how some older drugs might really provide unexpected medical benefit to large numbers of people.

Tranilast is one of those also-rans of the pharmaceutical world, notable mostly because a small Japanese pharmaceutical company sells it in Japan and South Korea as an asthma treatment. Several years ago, a unit of what later became GlaxoSmithKline tested the drug in a trial involving more than 11,000 patients, based on early evidence that it might prevent restenosis — the scar tissue that can re-block an artery after doctors wedge it open using balloon angioplasty or stents. Yet the trial failed earlier this decade, and tranilast slipped back into obscurity.

Until 2005, that is, when a team of Stanford researchers demonstrated that the drug could reverse paralysis in mice with a simulated form of multiple sclerosis. Tranilast, it turns out, bears a strong resemblance to a derivative of tryptophan — an amino acid found in turkey that was briefly (and wrongly) thought to encourage post-Thanksgiving sleepiness. These tryptophan relatives, however, did seem to have interesting effects on the immune system, which led a German postdoctoral student with funding from Angiogen to contact Stanford MS expert Lawrence Steinman and suggest that they test tranilast and other tryptophan derivatives against the disease in mice.

Not only did tranilast undo paralysis in the experimental mice, it appeared to alter their immune systems to the point that cells transplanted from a tranilast-treated mouse could also protect ward off paralysis in others. At the time, the scientists figured that tranilast might somehow tip the immune system away from an “attack” mode, in which T-cells ravage the myelin sheath that protects nerve cells in the spine, to a “quiet” mode that suppresses immune reactions. The group published their findings in the journal Science (subscription required).

Two years later, Angiogen has renamed itself Nuon — new CEO Rodney Pearlman, the former head of Saegis Pharmaceuticals, explains that the old name was already taken by another biotech — moved to San Francisco and raised its first round of funding. The company is pursuing human tests of tranilast in multiple sclerosis and in rheumatoid arthritis, which Pearlman said the drug also appears to treat in mice. The company expects to be raising a second round in the range of $25 million to $30 million in the fall, Pearlman says, in order to support those proposed human trials. GBS Venture Partners of Australia invested in Nuon’s first round..

There is, of course, no guarantee that tranilast will work in either of these autoimmune diseases or that it will ameliorate pain, another condition the company is pursuing. Scientists have cured diseases like MS many times in mice, but never in humans. Tranilast also isn’t a perfect drug from a commercial standpoint, since its patent has long since expired. Given that it’s never been marketed in the U.S., however, there’s no generic version available to compete with it, notes Pearlman, who adds that Nuon has taken out “use patents” to cover treatment for autoimmune and other diseases.

Whether the drug succeeds or not, the tale of tranilast presents an interesting example of what can happen when enterprising scientists explore potential broader uses for an older drug against debilitating chronic diseases. (That alone sets it apart from many specialty pharmaceuticals, which are often “me-too” drugs that target fairly narrowly defined conditions.) In addition, the fact that tranilast has already been tested so thoroughly means that the basic safety of the drug has already been established. “The beauty of a drug with a long history is that you can jump into some advanced trials,” Pearlman says. “You don’t have to go and do all the slow things with it.”

For further reading, this Stanford News Service article and this Stanford Daily piece provide some good background on the drug.