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This article was published in U.S. 1 Newspaper on November 17,
1999. All rights reserved.
Mom & Pop Management for a Hot Biotech
This mouse doesn’t roar. It just does its job —
manufacturing a therapy for almost any disease. Vaccinate this special
mouse with a diseased cell, and the mouse can create antibodies to
fight that disease. Let one of those antibodies multiply, and it will
produce quarts and gallons of disease-fighting antibodies to cure
Medarex owns this special drug discovering mouse, plus several
like it, and licenses them to pharmaceutical companies. Medarex, a
biopharmaceutical firm that has just resurfaced in Princeton, also
does its own research on monoclonal antibody-based therapeutics that
can fight diseases. (Monoclonal antibodies bind selectively with a
villain cell, such as cancer, without affecting healthy neighboring
cells and with minimal side effects.)
In 10 years Medarex has grown from a $3 million private company with
shaky financial underpinnings to a $300 million public company with
an encouraging future. The biopharmaceutical firm was formed at
in 1987, opened at 20 Nassau Street in 1989, went public and moved
to Chambers Street in 1991, left town to set up in Annandale in 1995,
bought a genetically perfected mouse in 1997, and has just moved its
corporate headquarters back to Princeton, to Princeton Gateway at
707 State Road. It trades on Nasdaq as MEDX.
As the CEO of Medarex, Donald L. Drakeman presides over this rodent
kingdom, and he believes the drugs developed from these mice could
revolutionize treatment for hundreds of diseases. His partner in this
revolution is his partner in life, Lisa Natale Drakeman, senior vice
president for business development. The Drakemans are trying to push
their technology to the top of the heap: "We think that human
monoclonal antibodies will be the dominant drug technology over the
next 10 years, and we want to be the leader in trying to do that,"
says Don Drakeman.
"We established a very strong technology with the mouse we
as the Hu-MAb Mouse, and we now have 14 partners with that technology
and use it inhouse as well," says Lisa Drakeman.
Since the Drakemans and Medarex’ chief financial officer, Michael
A. Applebaum, live in Princeton, the move to Princeton is going to
save lots of time, but it was triggered by the landlord’s decision
to take back some space that Medarex was leasing in Annandale. The
move will be good for business reasons as well personal ones, says
Lisa Drakeman. "We are trying to put this mouse technology in
as many hands as possible, and it will help to be here in the thick
of the New Jersey biotech industry and convenient to financial
It is close to downtown, and people can get to transportation
She worked with Buzz Woodworth of Nassau Street-based Keller Dodds
& Woodworth to find the 6,000 square foot Princeton Gateway space,
formerly leased by Technology Management & Funding. For this
Medarex will be hiring 8 to 10 people, she says. It currently has
90 employees in four locations including those in Utrecht, the
and at the "mouse farm" GenPharm International, in California.
Applebaum doubles as president of GenPharm, and Lisa Drakeman is CEO
of the spinoff that Medarex owns in Copenhagen, Denmark, called GenMab
Antibody therapy was so new, 10 years ago, that Medarex hosted a
to help introduce it to the scientific community. Two years ago
added the bioengineered mice to its portfolio. A drug analyst at
and Quist predicts that revenues from the mouse-produced antibody
market — including those from Medarex and a competing firm —
will total $3.1 billion by 2002.
So far Medarex has been involved in work on three dozen therapies.
Working in three areas — cancers and leukemia, autoimmune disease,
and ophthalmology — Medarex has seven monoclonal antibody products
in clinical trials. Beyond that, it has licensed its technology to
13 partners (including Amgen, Bristol-Myers Squibb, Centocor, Immunex
Corporation, and Schering AG) involved in more than 30 different
programs. Just announced: a 10-year license to Novartis that started
with payment of more than $3 million in stock and could go up to $50
Drakeman scrimped in the early years to preserve the
company’s patent position and enhance it with the purchase of the
GenPharm mouse technology. So he is in the fortunate position —
unlike some of his peers — of being able to resist a buyout.
you develop an attractive business there is always the potential that
someone will want to buy you," he admits. "But rather than
be bought by one company we would prefer to partner with them all.
"We think it is more cost effective to rent us rather than buy
us, and we will ultimately achieve much more value for our
to have two to three dozen companies developing products from our
technology than just one," says Drakeman. "We want to give
it a chance to be used in many different places, to deliver new and
better treatments to as many different people as possible."
How do you rent a mouse? "Our basic strategy is breed them, feed
them, and mail them," says Drakeman. "We maintain control
of the breeding and make the mice available to our partners. They
can take a license to our technology and our patents for specific
antibodies they want to make."
Typical licensing and milestone payments are in the range of $10
"We don’t charge by the whisker. They get as many as they need
— they will use a handful of mice, though they really need only
one." In addition to the 6,000 foot lab in San Jose, Medarex has
colonies in New York and the Netherlands, rents a small amount of
mouse space from Rutgers, and stores embryos at other locations.
Mice are fastidious by nature but these 5,000 mice are extra clean;
they sleep on sawdust that has been sterilized by an autoclave and
eat food that has been irradiated. They are handled with forceps by
caretakers who shower before donning sterile gowns and masks.
Because mice take better care of their young when they live
each breeding cage has two females and one male. After a gestation
period of three weeks, the infants are born as big as the tip of a
little finger, hairless, pink, and blind. Weaned and hirsute at six
weeks, the mice (usually female, because they don’t fight with each
other) are eligible to travel, at eight weeks in lots of six or seven
via a courier service. "Mice travel light and travel well,"
Drakeman says that the particular technology for making antibodies
by vaccinating mice was invented by Cesar Milstein and Georges Kohler.
"The difficulty people
didn’t anticipate was that the `mouseness’ of the antibodies was going
to be a problem." The tiny bits of mouse protein contained in
the antibodies could cause an immune response that might include fatal
Whereas other scientists tried to make the mouse antibodies "look
more human," Nils Lonberg of GenPharm in San Jose worked on
the factory, i.e. genetically engineering the mouse so it produced
human-like antibodies. "We leapfrogged that whole technology by
engineering the mice instead the antibodies," says Drakeman.
replaced some of the mouse genes with human genes, so the antibodies
that the mouse makes are 100 percent human. It happens quicker,
and more reliably than by manipulating the antibodies."
Lonberg, an alumnus of Reed College, Class of ’79, with a PhD from
Harvard in molecular biology, met Drakeman in 1997 when Medarex bought
GenPharm, paying $65 million in stock and receiving half of that sum
back in cash.
Only one other company claims rights to transgenic mice that produce
human antibodies, archrival Abgenix (ABGX), which raises its own
called XenoMouse, in Fremont, California. Lonberg published his
in Nature in 1994, and Abgenix filed a trade secret lawsuit, which
triggered a counter patent suit. Before Medarex bought GenPharm, the
issue was settled. Abgenix and its parent, Cell Genesis, made a
$40 million payment to GenPharm. "We felt our technology was
because our mouse has almost all the human genes in it," says
Kurt Leutzinger, chief financial officer of Abgenix. "But we
the freedom to operate. Rather than wait for the patent situation
to clear up we each cross licensed the other’s patent."
"As a private company," explains Lonberg, "we had a
amount of money and had restructured from 100 people to 7 people.
We wanted to end any cloud of uncertainty over the license." He
retains key patents to most methods of making transgenic mice that
produce human antibodies.
This is how transgenic mice do their work: Lab technicians immunize
the mouse by taking, for instance, a breast cancer cell and
the mouse with that cell. The technician injects the mouse with a
protein from that certain type of breast cancer. Over a period of
one to two months the mouse makes an immune response by creating
cells called B cells. Because the mouse has had its antibody-producing
gene replaced by a human gene, these antibodies are not likely to
cause immune reactions, so they can be administered repeatedly.
When the B cells fuse with another cell, the result is a hybridoma,
which essentially lives forever. "It will spit out antibodies
as long as you feed it," says Drakeman.
"Usually you immunize one mouse with one thing you are interested
in. That mouse will make dozens of different antibodies, and you test
them. Some will bind more tightly than others. Some will bind just
to that breast cancer and not to anything else. Some make cells more
efficient. You select from several dozen the one you like the best,
put it in a fermenter, make vats of that, and use it for the breast
cancer patient," says Drakeman. Antibodies are typically
intravenously every week or a couple of weeks for several months.
Medarex is in a particularly good position to work with mouse-based
monoclonal antibody therapy because it pioneered in that and also
in a similar therapy, bispecific antibodies. Bispecific antibodies
can accelerate treatment. "There are times when you want to
the ability of the antibodies to access the immune system," says
Drakeman. "We `glue’ a tumor cell antibody to a cell that triggers
the immune system or blocks the immune system."
A natural leader, the six-foot two-inch Drakeman trained
as an attorney, but he is also a religious ethicist and a musician,
and his work at Medarex has drawn on each of these fields. But he
attributes his success to his upbringing: "My parents were
supportive of me," he says. "They made me believe that I could
whatever I could set my mind to. They gave me the confidence to be
an entrepreneur and keep plugging ahead on treatments of life
His father, Fred, was a plant manager for RCA in Haddonfield and then
for a gas pump manufacturer in North Carolina and the United Kingdom.
His mother, a homemaker, died last year. When the family moved from
New Jersey to North Carolina, Don was an 11th grader, but his
soon surfaced. He and two of his new friends organized Greensboro’s
first-ever youth symphony.
Don met Lisa when both were freshman, she at Mount Holyoke, he at
Dartmouth. Lisa grew up in Warren, Pennsylvania, where her father
was a forest ranger and her mother founded a jewelry store. Don played
trumpet in Dartmouth’s marching band and wrote the band’s comic
routines. Don and Lisa married three months after graduation in 1975.
He earned a law degree from Columbia in 1979 and worked on Wall Street
for Milbank Tweed, where he had his first legal experience involving
animals — a circus at Lincoln Center. When the circus caught fire,
and the pet dog for the baby elephants ran away, never to return,
the elephants refused to perform. To negotiate the contract Drakeman
had to determine the monetary value of the dog.
In 1982 he became general counsel of Essex Chemical, and in the 1980s
both he and Lisa earned their PhDs in religious history at Princeton
University. His thesis became a book detailing the separation between
church and state. (In spite of all his other duties, he teaches an
undergraduate seminar entitled "Civil Liberties" at Princeton
on an as needed basis; his course is scheduled for the spring semester
It was when Drakeman returned to Dartmouth for a marching band reunion
that he was introduced to the scientific powers behind Medarex,
W. Fanger, Edward D. Ball, and Paul M. Guyre. "I ended up involved
in biotech at Essex Chemical because my roommate — whom I met
in the marching band — was a professor at medical school who
a consultant to Essex."
With the cooperation of Nathan Dinces, Dartmouth’s director of
sponsored research, Medarex was founded as a joint venture between
Essex and Dartmouth. When Dow Chemical bought Essex in a hostile
Drakeman and the Dartmouth researchers bought out the company.
left Essex in 1989 to go with Medarex full-time and moved the company
to Princeton in 1990.
In 1992 when Medarex was in the middle of selling its second round
of stock on Nasdaq, Drakeman was confronted with a very unusual
— an anonymous letter to Dartmouth contesting the ownership of
the technology. Taking an extremely conservative position, Medarex
halted trading on the stock and resumed trading days later when an
investigation found the claims to be groundless.
Also that year, Lisa began working full time, when the second of their
two daughters — now at Hun — was in first grade. (Their older
daughter now attends Princeton University.) Lisa Drakeman has played
a prominent role in the biotech community; she was appointed by
Whitman as a commissioner of Prosperity New Jersey, and she was named
Advocate of the Year by the Biotechnology Industry Organization. Lisa
is CEO of GenMab, the Danish spin-off, and on November 15 she
that GenMab doubled its available financing by obtaining a loan
from the Danish Growth Fund for about $7 million.
In the biopharm field, very few husband-wife pairs can be found
jobs and family. How do they manage? "It’s easy," says Don
Drakeman. "We work all the time."
"This is such a demanding field," says Lisa, "that it
helps for both of us to be in it. We understand the pressures on each
other, and this is something we share instead of being divided by
Don recalls a time when they went to a swim meet where one of their
two daughters was competing. "One of the other parents said to
us, `You two talk to each other too much to be a married couple. What
do you talk about?’ I turned and said, `Loyalty rates, milestone
"Jobs like the ones we have, in the entrepreneurial field,
are very all encompassing. You don’t just do it 9 to 5 or even 9 to
9. We have found it to be a wonderful thing to be able to share what
is important at the office and what’s important at home at all times
of the day and night," he says. "What we do is very
and to be able to work with very talented people is important and
a real blessing. Our management team is a group of really talented
The Drakemans’ management team has attracted some well-known
Junk bond king Michael Milken’s charity, dedicated to the cure of
prostate cancer, funded initial work on prostate cancer. A San
merchant bank, Bay City Capital, put its largest single investment
— $27 million — into Medarex. The bank is 50 percent owned
by the Pritzker family, the Hyatt hotel founders known for medical
philanthropy. "When we make an investment, management is the first
thing we look at, and technology is the second," says Fred Craves,
a partner with Bay City Capital.
Medarex has a ways to go. Its mice are busy at work both inhouse and
for other companies, but its rival, Abgenix, has attracted more than
twice as much investment capital. The monoclonal antibody drug
market is hot — most of the drugs approved in the last couple
of years are based on it — but of the eight monoclonal
drugs available now, none are by Medarex; Medarex products are still
in the pipeline.
Still, Don Drakeman is satisfied: "We are treating a significant
number of patients in clinical trials and have seen a number of
have life changing experiences as a result of our work," he says.
"Prostate patients with a life expectancy of a few months, under
our treatment, continued with dramatically lowered pain levels and
disease levels for well over a year. That is really gratifying."
The Drakemans are fond of their HuMAB mice, but they keep none as
pets. "We have four cats," he says.
Suite 206, Princeton 08540. Donald L. Drakeman, president.
fax, 609-430-2850. Home page: www.medarex.com.
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