iPierian Zeroes In on Antibodies for Alzheimer’s, Neurodegeneration

Xconomy San Francisco — 

iPierian used to be known as a stem cell company, when stem cells were all the rage. But now it’s taking on a new identity as an antibody drug developer that happens to use stem cells as a tool for discovery.

The South San Francisco-based company is announcing today that it has found a new direction under CEO Nancy Stagliano, who took over back in September. The company is now zeroing in on making antibody drugs for neurodegenerative diseases like Alzheimer’s, which are affected by the Tau protein and the Complement biological pathway.

iPierian is also announcing today it has hired Pamela Conley, the former vice president of research at South San Francisco-based Portola Pharmaceuticals, to oversee the iPierian stem-cell technology and the tangible drugs that are supposed to come out of it.

The shift shouldn’t be that surprising. Stagliano is a neuroscientist by training, her last startup (South San Francisco-based CytomX Therapeutics) is an antibody drug developer, and Big Pharma companies are desperately searching for anything half-decent at slowing down neurodegenerative diseases like Alzheimer’s. The work at iPierian is still very much in the early stages, as Stagliano says she hopes to enter clinical trials in 2014.

If the company can do that, it would be a step ahead for the use of so-called induced pluripotent stem cells (IPSCs) for drug development. And it would give iPierian’s prominent crew of backers—including Kleiner Perkins Caufield & Byers, Google Ventures, and GlaxoSmithKline’s SR One—a new shot at getting a return on more than $50 million in investment. The company has gone through a series of strategy shifts in its brief history, as it had five CEOs pass through in its first three years.

Nancy Stagliano

“My big vision is this is the tip of the iceberg for IPSC cells,” Stagliano says. “We’ve made a lot of progress with the platform in Alzheimer’s and the disease models we’ve created. Because of that success, we’ve narrowed down and prioritized these two areas. We’re going where the science is taking us.”

Scientists at iPierian over the last six months have spent time working to make stem cell technology useful for drug development. The basic idea is to take ordinary adult cells like those from skin or blood, and reprogram them into a stem-cell state so they can be coaxed to differentiate into any other cell in the body. By doing that, scientists have found they can make adult human neurons in the lab dish, which can be used as models to see what happens in disease, or how drugs might interact with actual neurons.

Using cells from many different individuals also gives scientists a better idea how the disease varies from person to person, and how different molecular subtypes of disease might respond differently to certain targeted therapies.

iPierian has used its stem cell technology in recent months which has given it new insights about targets to go after on the Tau protein and in the Complement pathway, Stagliano says. While most Big Pharma companies are focused on reducing the accumulation of amyloid beta plaques as a way of fighting Alzheimer’s or frontotemporal dementia, some scientists believe the accumulation of tangles of Tau proteins might be just as important to the disease. Drug companies are also targeting Tau, but most are focused on making conventional small molecule drugs against biological targets inside cells, Stagliano says.

Based on insights it has gotten from its IPSC technology, iPierian says it believes it has found a target on the surface of cells, which is an accessible area for antibody drugs. Stagliano isn’t naming the precise target, but she says the company is actively screening antibodies against it, and should have a lead drug candidate to push through preclinical drug development by later in 2012.

“This is big news for us,” Stagliano says. “These are complementary approaches, and it’s not clear yet which will win.”

The Complement pathway is known to immunologists for playing a key role in the innate immune system, and the promotion of inflammation that can be good (fighting off infections) and bad (autoimmune disease). Scientists are also beginning to better understand that Complement activation can be associated with neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease.

Through its IPSC technology, iPierian’s scientists have looked at how various brain cell types—neurons, astrocytes, microglia—are affected by variations in the Complement pathway. The company has identified a couple of targets through the Complement pathway—again, which it isn’t naming—that it believes have potential for drug development. “To our knowledge no one is developing drugs to these targets we are focused on,” Stagliano says.

Moving those programs through development will naturally take money. The company, which last raised a $28 million venture round in September 2010, will look to raise another round later this year, Stagliano says. If iPierian can do that, it will be based on its ability to hit traditional milestones of progress for antibody drug development, not on general excitement about the potential of stem cell technology. While the new direction probably won’t make the cover of any national magazines, Stagliano says she’s excited.

“I came into the company not exactly clear what direction we’d head, but it’s been fun to see these data evolve and these directions evolve,” Stagliano says. “We really are going where the science is taking us.”