Satori Cultivates Prolific Herb for Promising Alzheimer’s Weapon

2/28/12Follow @arleneweintraub

Alzheimer’s drug developer Satori Pharmaceuticals raised $15 million last week, bringing its total venture capital raised to $37 million—an impressive haul, considering the Cambridge, MA-based company doesn’t expect to begin human testing of its lead compound until early 2013. But what may be even more notable is that Satori’s investors are betting on an entirely new source of Alzheimer’s-fighting compounds: black cohosh, a flowering herbaceous plant that’s most commonly marketed as a nutritional supplement to relieve symptoms of menopause, such as hot flashes.

Satori was founded in 2005 around a discovery made at the Mayo Clinic in Jacksonville, Fla. Scientsts there separated out and then scrutinized the components of black cohosh, until they hit on one that would act against amyloid beta 42—a protein believed to cause the damaging brain plaques that characterize Alzheimer’s. The key attribute of the compound the Mayo researchers found, says Satori CEO Jeff Ives, is that it appears to inhibit the toxic protein without interrupting normal brain functions. “They just went hunting for all the compounds no one has ever characterized—the novel structures,” Ives says. “The extract they came up with looks like dark purple stuff, but it’s made in heaven.”

Amyloid has long been a sought-after target in Alzheimer’s drug development, but it’s been a challenging one to tackle. Most attempts to reduce the buildup of brain plaques have sought to inhibit a family of amyloid-promoting enzymes called secretases. Problem is, secretases are present in cells all over the body and are necessary for various functions, so broadly blocking them can cause dangerous side effects. In 2010, Eli Lilly stopped developing a secretase inhibitor it was working on because it seemed to increase the risk of skin cancer in patients participating in its trials. “You can’t just take a hammer to these enzymes,” says Jeff Jonker, Satori’s chief business officer. “There are places in the body where they are needed for normal functioning.”

In animal studies, Satori’s compound has proven to be highly selective—meaning it binds with a specific enzyme called gamma secretase, in turn blocking amyloid beta 42 without affecting normal proteins. The company hopes to be able to intervene early, maybe even before patients have symptoms, to kill the “bad actor” in Alzheimer’s, Ives says. “What we want to do is stop the first step in the formation of plaque,” he says.

Black cohosh is a perennially blooming plant that has been used since the 1800s to treat everything from sore throats to depression. Natural-medicine practitioners believe it’s the estrogen-like compounds in the plant that relieve menopausal symptoms. But the plant’s Alzheimer’s-fighting properties are not related to estrogen, Ives says. “The molecule found at Mayo is a minor constituent of black cohosh that modulates gamma secretase,” he says. “It’s a unique chemical series.

Satori’s staff of 11 scientists took the raw material from Mayo and spent years figuring out how to make it into a safe, effective drug, Ives says. They used medicinal chemistry techniques to produce a molecule that could get beyond the notoriously impenetrable blood-brain barrier, and that could be made into a drug patients can take by mouth. Satori plans to file an application to the FDA later this year for permission to begin human trials.

Much of Satori’s development strategy hinges on a multifaceted plan to prove out the molecule’s attributes in animal models, says Chris Ehrlich, general partner at InterWest Partners in Menlo Park, CA, one of the startup’s original investors. That’s because Satori wants to attract a deep-pocketeddevelopment partner as early in the process as possible. “Our hypothesis is if we can prove out pre-clinically that the molecule behaves, in multiple animal species, there will be partners who are interested before the drug ever sees a human being,” he says.

Satori’s management team is so intent on signing on a Big Pharma development partner early that they hired Jonker two years ago and sent him out to cultivate relationships that may lead to development deals. The company is very open, Ehrlich says, about how it’s running the animal studies, and it regularly seeks feedback from potential pharma partners. “We say, ‘Here’s what we’re doing, tell us what you need to see. We’ll build it if you come,’” Ehrlich says.

A number of pharmaceutical and biotech companies are trying to develop more effective treatments for Alzheimer’s, which is considered among the world’s biggest unsolved medical problems. More than 5 million people in the U.S. alone suffer from the disease—a figure that’s expected to skyrocket with the aging of the population. One of the most widely watched experimental treatments is bapineuzumab, a drug being developed by Pfizer and Johnson & Johnson that’s now in late-stage trials. And last December, Merck unveiled an early-stage compound that works against an amyloid-promoting enzyme called BACE.

Ives believes that even if those companies don’t want to partner with Satori, the more competitors in the Alzheimer’s space the better. “I expect if Merck is successful with a BACE inhibitor we could have a combination product,” he says. “It’s two different ways of skinning the same cat—we’re both shutting off these neuro-toxic peptides.”

But Satori has a long way to go to prove its compound works. Because its drug will be designed to be taken chronically, starting at the early stages of the disease, Satori will have to run large and lengthy trials to prove it’s safe. “This is a tough population,” Ives says. “They’re in their seventh or eight decade of life and on a multitude of drugs for treating other things like heart disease and arthritis. We don’t want drug interactions. This has to be mother’s-milk clean and safe to be taken for years.”

InterWest Partners, New Enterprise Associates, and Prospect Venture Partners led Satori’s most recent funding round, which will be deployed towards the company’s goal of collecting enough pre-clinical data to generate a Big Pharma deal. Jonker and Ives say they expect to have some data ready to present at the industry’s big annual confab—the Alzheimer’s Association International Conference in July. Although they have a bit more work to do, they remain confident someone will be willing to take on the risk of developing their black-cohosh derived drug. “There’s been a lot of interest,” Jonker says. “The magnitude of this disease in terms of its impact socially and economically, relative to the drugs the industry has been able to produce is out of whack. This is the largest unmet medical need right now.”

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