Zinfandel Pharmaceuticals, a Chapel Hill company headed by eminent scientist Allen Roses, has staked out the ambitious goal of revolutionizing the medical community's approach to Alzheimer's disease.
Armed with a deal announced earlier this year with Takeda Pharmaceutical, Japan's largest drug company, Zinfandel is gearing up for clinical trials designed to demonstrate that Takeda's drug Actos - a prescription medicine for diabetes - can delay the onset of Alzheimer's.
The key to that deal, which calls for Takeda to pay Zinfandel $9 million up front and up to $78 million for reaching development milestones, is Zinfandel's patents for TOMM40, the second gene linked to an increased risk of Alzheimer's disease.
Roses led a team of scientists who made that discovery after retiring as a senior vice president at GlaxoSmithKline, an effort that included spending nearly $500,000 for one experiment that he funded with a home equity loan.
Roses, 68, said of his decision to finance the research: "I've had two heart attacks. I do have a pacemaker. Ever since 1990 when I had the first one, which was [very serious], I don't take prisoners."
Roses also is on the faculty at Duke University, where he is Jefferson-Pilot Professor of Neurobiology and Genetics, among other roles. During an earlier stint at Duke, he led the team of gene hunters that, in 1992, made the blockbuster discovery linking Alzheimer's to the APOE gene.
But one of the variants of that gene, APOE4, is only useful for predicting half the cases of late-onset Alzheimer's. However, TOMM40 can account for more than 90 percent of Alzheimer's cases, Roses said.
The clinical trial that Zinfandel is planning aims to confirm TOMM40's ability to predict the onset of cognitive impairment of Alzheimer's and demonstrate that Actos can delay its onset.
"This is a really unique opportunity for an existing product that we know is very safe," said Arthur Pappas, founder and managing partner of Durham venture capital firm Pappas Ventures. "If the clinical trials are [successful], it will have a profound effect on medicine, on Alzheimer's patients'... quality of life."
Pappas Ventures represented Zinfandel and Roses in the negotiations with Takeda; Pappas Ventures isn't an investor in Zinfandel, which is 100 percent owned by Roses.
Actos lowers blood glucose levels by stimulating the growth of mitochondria - the cell engines that metabolize glucose. The theory is that by stimulating the growth of mitochondria in the brain, Actos can delay Alzheimer's ability to kill brain neurons.
The worldwide clinical trials, which will take about five years to complete, will involve 4,000 patients ages 62-83 who today have "normal" brain function as defined by standard neuropsychological tests. Half the patients who are diagnosed as high-risk for Alzheimer's - thanks to the predictive ability of TOMM40 - will receive Actos, while others will receive a placebo. They will be tracked to see when "cognitive impairment" - the first visible symptoms of Alzheimer's - materializes.
"The idea is, do we make a difference in delaying the onset of the disease?" Roses said. "Can we make a difference by giving Actos and increasing the metabolism of the brain?"
If the answer is yes, Actos' label would call for testing for Alzheimer's risk via the TOMM40 genetic marker, Roses said. Takeda's deal with Zinfandel gives it the exclusive commercial rights to TOMM40.
In addition, a group of low-risk patients, who also will receive placebos, will be tracked to confirm the predictive ability of TOMM40.
Roses formed Zinfandel in 2008, but it was a virtual company until the Takeda deal was negotiated.
Today Zinfandel has about a dozen employees but remains largely invisible. It occupies space in a Chapel Hill office building rented from a provider of offices, conference rooms and related services. Consequently, Zinfandel's name isn't even on the door. Nor does the company have a website.
"I don't need to invest in that," said Roses. "I'd rather invest in the study."
That includes an investment in personnel. Five Zinfandel employees previously were senior vice presidents or vice presidents in drug development at GSK or other large pharmaceutical companies.
In addition to the up to $78 million in development milestones Zinfandel could receive, the deal with Takeda calls for Zinfandel to receive royalty fees pegged to sales if Actos win approval as an Alzheimer's medicine. In addition, Zinfandel would receive unspecified commercial milestones that would kick in, for example, if Actos is approved for Alzheimer's prevention in certain markets and for commercial launch of the product.
Roses said that, if all goes well - a huge if in the risky world of drug development - the commercial milestones would be worth more than five times the development milestones.
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