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Satori Pharmaceuticals shuts down after failure of Alzheimer's drug

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Satori Pharmaceuticals has closed its doors after running into safety problems in preclinical research of its lead program for Alzheimer's disease, FierceBiotech has learned.

The Cambridge, MA-based biotech startup, which had raised $40 million from leading venture investors, had researched small-molecule modulators of the gamma secretase enzyme as a way of reducing amyloid beta 42 (AB42) peptides. The AB42 peptides are a main component of brain-damaging plaques found in patients with Alzheimer's disease, which has befuddled drug companies through a series of research failures and setbacks.

Satori was derailed from an expected initial clinical trial of its lead candidate in late 2012, when a study of a compound in monkeys found that it disrupted adrenal function and the company's backup compounds presented the same "physiochemical" problem, Jeff Jonker, who was chief business officer of Satori, told FierceBiotech in a phone interview on Thursday. The side effect was completely unexpected and unrelated to the gamma secretase target, he said.

The company had already laid off most of its scientists late last year in anticipation of transitioning from preclinical to clinical development of the lead gamma secretase modulator, Jonker said. Through the first three and half months of this year, the company's remaining staff of 5 employees stayed on as the board and executive team weighed options for the business, including partnerships and acquiring other assets in the Alzheimer's field.

"The bottom line was that nobody could see a scenario where it made sense to put more money in to keep prosecuting this program for another couple years before you even knew if you had an IND candidate or not," Jonker told FierceBiotech.

Satori had already gone back to previous investors InterWest Partners, New Enterprise Associates (NEA) and Prospect Venture Partners for a $15 million round announced in February 2012. The $15 million financing was supposed to support Satori ahead of the planned clinical work that never materialized because of the safety problem in the monkey study. Its website also lists PureTech Ventures as an investor.

Jeff Ives, who joined Satori in 2008 as CEO after a career in senior research posts at Pfizer ($PFE), deferred comments about the company to Jonker on Thursday because he was attending a family event.  

The venture-backed biotech startup's gamma secretase program has become another casualty of the largely losing campaign across the pharma industry to find safe and effective treatments to combat memory-stealing Alzheimer's. Part of the challenge has been the difficulty in understanding the complex disease, with the causes and biology of the ailment still under debate in the scientific community.

"I think we fundamentally lack an understanding of the pathogenesis of this disease," Jonker said. "And because we lack an animal model that replicates the human biology, we really are flying blind preclinically." 

While Satori has dropped out of research of gamma secretase modulation, Jonkers said that he thinks the target is worthy of further research. Others in the industry agree. In January, Watertown, MA-based Envivo Pharmaceuticals began a Phase II study of a selective modulator of gamma secretase called EVP-0962 with the goal of measuring its impact on amyloid levels in cerebrospinal fluid of patients. Bristol-Myers Squibb ($BMY) and Eisai have also researched drugs that work in a similar way to treat Alzheimer's.

The companies have held out hope for modulating the enzyme target because all-out inhibition of gamma secretase came up short. Last year Bristol-Myers threw in the towel on a gamma secretase inhibitor called avagacestat, which failed a Phase II study because of weak evidence of efficacy. Eli Lilly ($LLY) slammed the brakes on Phase III development of an inhibitor of the target called semagacestat in August 2010 after data showed that Alzheimer's patients on the compound fared worse than those on placebo and showed increased risk of developing skin cancer.

Lilly, Bristol-Myers and others have stayed committed to the Alzheimer's field in hopes of serving a huge market with new therapies. There are 5.4 million Americans who suffer from the dementia, and available treatments only delay symptoms rather than reverse the decline in mental functions, according to the Alzheimer's Association.

Even sad stories like the failure of Satori's lead program won't keep others from jumping into the hunt.  

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