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This article by Barbara Fox was prepared for the June 30, 2004

edition of U.S. 1 Newspaper. All rights reserved.

The Stocks’ Unusual Family Farm

When you talk about a family business you think of an enterprise that

was passed from grandfather to father to son. You also think of a

retail or manufacturing business or even a law practice. You don’t

think of a biotech startup run by two brothers and one of their sons.

Two brothers in a biotech — and they are not scions of the

pharmaceutical industry? Unlikely, but happening.

Jeff and Greg Stock went to Johns Hopkins, graduating in 1968 and 1971

respectively, with Jeff majoring in biochemistry, Greg in biophysics.

Then they went their separate ways. Jeff stayed in the lab and came to

Princeton University, and Greg combined bio with business, turned his

attention to public policy, and became a best selling author, starting

with the “Book of Questions” series.

Together the brothers have started Signum Biosciences at Princeton

Corporate Plaza. The core technology comes from Jeff’s laboratory and

is licensed from Princeton University. Maxwell Stock — Jeff’s son, and

Greg’s nephew — is the vice president and runs the lab. Greg is the

president and CEO.

“We waited a long time to go into business together,” says Greg Stock.

“I had always heard it was not a good idea to go into business with

the family.”

“The exchanges that we have on strategic issues — related to the

science we are trying to drive, the finances and how we are

approaching it — are very creative,” says Stock. “When you really

trust people, you can argue, discuss things, fight about them, and

ultimately come up with a strong product. You don’t have to watch your

back. Someone is going to tell you when you are out of line, or when

you are full of it. We have an intimacy of connection on every aspect

— science and business — functioning on day to day basis.”

By modulating a key regulatory process known as reversible protein

methylation, Signum Biosciences hopes to develop a whole suite of

therapeutics. In addition to working on pharmaceutical and botanical

drugs for Alzheimer’s and other dementia, Parkinson’s, and a new class

of anti-inflammatories, Signum might also produce nutritional

supplements that would be available to consumers much sooner.

About 10 people work here now, including those brought in from the

outside, and the Stock brothers are tapping their networks for

consulting services. Greg Stock, who is the spokesperson for the

company, is moving with his wife to Princeton from California.

Recently the brothers expanded the laboratory from 1,000 to 2,000

square feet at Princeton Corporate Plaza. “Having an incubator

environment is what we need, and the landlord is very supportive

here,” says Greg Stock. “We moved to larger space seamlessly.”

Stock says he bases his pitch to investors on his brother’s and his

own reputation and a “really solid” business proposal, “what we are

doing and how we will go about doing it.”

The company raised its first round of financing and will be going for

a Series B round in late fall. The initial $1.5 million came from

angel investors with whom Greg Stock had had previous contacts. They

include Pierluigi Zappacosta (the founder of Logitech) and the unnamed

owner of a hedge fund in Princeton.

Angel money is good, venture capital money is not, Stock believes.

“Venture capital money wants all sorts of control, and what is

important about this company is that we really have control. It is

difficult when business people don’t understand your science.”

One way not to have to tap venture capital is to spend carefully. “We

have a modest burn rate,” says Stock, who has seen indications that it

is easier to set up a company on a small budget than a big one. Some

companies that raised a lot of money in the beginning have gone out of

business because they had bad spending patterns. “I can think of one

that had $40 million and is no longer here.”

Signum is using screening tools, developed in Jeff Stock’s lab and

licensed from Princeton University, to work on both drug therapies and

dietary supplements. “We have identified certain botanicals (plant

extracts) that are likely to contain therapeutic agents for

Alzheimer’s and other diseases that we are interested in.”

“The fact that some of them have had a strong effect on the

biochemistry we are targeting has validated our confidence in our

screens,” he explains. “Now we are going in to see how these compounds

actually work, not only in vitro — we are proceeding to tissue culture

and mouse model experiments as well.”

“The key has been to find the right compounds to investigate. We are

looking at the biochemistry of two major sites where reversible

protein methylation occurs, and exploring how this affects critical

regulatory pathways, and this approach is proving very fruitful. We

have already identified a new class of anti inflammatories and a

strong therapeutic candidate for Alzheimer’s, which is pretty damn

exciting,” says Stock.

“Although we have been successful in mining the botanical realm, which

incidentally is the source of almost half of our current drugs, we are

not neglecting the traditional pharma libraries.”

One source of new compounds could be Signum’s collaboration with Ilya

Raskin and other researchers from Rutgers to screen plant extracts

from Uzbekistan and Kyrgyzstan. Signum is one the screening partners

for the $3.5 million, five-year grant by the Interagency Biodiversity

Program, and it will do assays for mental disorders and

anti-inflammatories using its proprietary methlyation screens.

But Stock notes that the company’s early work is showing that many of

the most interesting active botanical compounds are in plants that are

already well known, the ones “right under our noses,” he says.

“Searching among agents with a long history of human use gives us a

jump start. When we find agents in these products they are essentially

prequalified, and we are much more likely to have something that

eventually will turn into a useful therapeutic,” says Stock.

“As a partner, Princeton University has been very cooperative,” says

Stock. Partnering with academe is a “one hand washes the other”

proposition. How it works: Scientists at a university do basic

research that is available for anyone to use. Then a biotech licenses

the research to make proprietary products.

“Feedback goes both ways. Some of the work we are doing is identifying

basic research problems that will be interesting to pursue in academic

collaborations,” says Stock. “It’s a virtuous circle. Effective basic

research produces understanding that can influence the product

development in the same way that our screening agents bring up

interesting topics for basic research.”

The hotbeds for these kinds of associations are in Stanford and

Boston. “These are the synergies that fuel real development in both

realms. But it seems like New Jersey is quite supportive,” says Stock,

who is applying for a New Jersey Springboard Development Grant.

The grandfather of Jeff and Greg Stock was a journalist. Their father

was an electrical engineer, and their mother majored in economics at

the University of Chicago. One uncle wrote a textbook on oceanography,

and another uncle wrote a physics text. “Our family valued research

and science a great deal,” says Stock.

Born three years apart, they moved from California to Arizona, but

spent their early teenage years in Great Britain, where they learned

to play rugby. They went to public high school in Baltimore and stayed

in Baltimore to attend Johns Hopkins.

Jeffry Stock did his biochemistry PhD with Sol Roseman at Johns

Hopkins, and a post doc in Berkeley with Dan Koshland Jr., for a long

time the editor of Science. A professor in the department of molecular

biology at Princeton for 20 years, he is a recognized expert on

bacterial chemotaxis (the ability of bacteria to sense specific

chemicals and move towards them). This led directly into his current

work in eukaryotic cell regulation, specifically reversible protein

methylation, which is an ancient regulatory architecture that is

critical to all cell-cell communication as well as many other

important cellular processes.

In 1992, with Arnold Levine, Jeff Stock co-founded Cadus

Pharmaceuticals, a company that operated in Manhattan from 1992 to

2000.

Jeff, who was not interviewed for this story, has two children,

Katherine is married to an attorney and lives in Colorado. Maxwell

went to the University of Colorado and worked at Synergen in Boulder.

He and his wife, Lisa, are expecting their second child. They moved to

Princeton because of Signum, and he is running the Signum laboratory

now.

Greg did his doctoral thesis in developmental biology (limb

regeneration in newts) at the University of California at Irvine. He

earned his Harvard MBA when he was 36 years old. About that time he

published his first “Book of Questions,” designed to prove one’s basic

values. A best seller, it became a series, and it sold 2 million

copies in 55 printings and was translated in 17 languages. Then Greg

Stock began writing about how technology and science will affect

society, starting with “Metaman,” on the merging of humans and

machines into a global super organism, published in 1993. His most

recent book is “Redesigning Humans: Our Inevitable Genetic Future.”

Lately he has focused on genomics and implications for public policy,

and he is called on to give keynote speeches at pharmaceutical

conventions. At present he directs the Program on Medicine,

Technology, and Society at the UCLA School of Public Health. Greg and

his wife, Lori Fish, and their infant daughter are moving to

Princeton.

Signum is not gearing up to groom itself for a quick sale, though Jeff

Stock’s previous company, Cadus, sold off its assets after only six

years. “We don’t have any intention of selling the company, though we

will eventually do an IPO,” says Greg Stock.

Along the path to drug development, the Stocks hope to spin off

various botanical extracts as dietary supplements. These

over-the-counter products, used for everything from wrinkle creams to

aching joints, can reach people quickly because they do not need FDA

approval, but they can make no medical claims, no matter how strong

the indications might be of their efficacy. The key here, says Stock,

is to be very sure about safety.

“Only where the risks are not significant because of a long history of

prior use and solid toxicology research, and only where the potential

rewards are substantial enough that we ourselves will want to take the

substance will we consider marketing a botanical extract as a

supplement,” says Stock.

The important thing will be to insure that any supplement is rooted in

strong science, that it is absolutely safe, “and that it has strong

enough indications of efficacy that the potential rewards far outweigh

the risks,” he says.

The company has already been in early discussions about potential

licensing of supplements to get cash flow, and Stock is exploring

marketing collaborations with consumer products companies.

A collaboration between brothers and son/nephew is indeed very

unusual, Greg Stock agrees. “It surprises me how well it is working,

that our expertises are so complementary, intersecting in a very nice

way. I really THOUGHT it would work. but sometimes things work even

more than you could have hoped, and that’s the case here.”

Signum Biosciences, 1 Deer Park Drive, Princeton Corporate Plaza,

Suite L-2, Monmouth Junction 08852. Maxwell Stock, vice president.

732-329-6344; fax, 732-329-8344. www.signumbiosciences.com


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