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This article by Barbara Fox was prepared for the August 28, 2002 edition of U.S. 1 Newspaper. All rights reserved.
Lisa Drakeman’s Human Antibodies
There will be lots of exciting technologies in our lifetime,
but making antibodies has a big future and the market is growing all
the time," says Lisa Drakeman, CEO of Genmab, which is headquartered
in Copenhagen but has administrative offices on North Harrison Street
in Princeton. "Antibodies will continue to have important uses
regardless of other therapies that other people invent."
Using genetically engineered mice, GenMab creates and develops human
antibodies for the treatment of life threatening and debilitating
diseases. In the three years since it was founded the firm has signed
a total of 10 partnerships, has a product in Phase III clinical trials
to treat rheumatoid arthritis, and is partnering with two other firms
for a breast cancer therapy.
Genmab licenses its mouse technology from Medarex, the 15-year-old
State Road-based firm founded by Lisa’s husband Don Drakeman. Lisa
Drakeman was vice president of business development at Medarex when
Genmab was formed. Genmab’s Danish investor-founders asked her to
leave Medarex to head the new firm.
Vaccinate one of GenMab’s mice with a diseased cell,
and the mouse can create antibodies to fight that disease. Let one
of those antibodies multiply, and it will produce gallons of disease-fighting
antibodies to cure human patients. Monoclonal antibodies bind selectively
with a villain cell without affecting healthy neighboring cells and
with minimal side effects.
Antibodies are particularly useful for fighting cancer, because cancer
cells masquerade as "regular" cells and lull the body into
thinking everything is fine. Antibodies work as the sentries in the
immune system. "Their job is go around, look for trouble, and
send a signal to other cells — to the white blood cells —
to `get over here and do something,’" says Drakeman. "They
look around for something that doesn’t belong there and they attach
to it, signaling the rest of the immune system to jump on."
Monoclonal antibodies can be coupled to a drug, a toxin, or an isotope.
Or if they target various receptors on tumor cells, they can be used
by themselves. How the Genmab process works: the mouse gets vaccinated
with a purified version of a particular target, a cell from a tumor,
as well as with whole cancer cells. "This gives us a very good
response and lots of antibodies," says Drakeman. "We grow
up the cancer cell in an `in vivo’ model, and we are looking for the
antibody that kills the cancer the best. We might have 50 antibodies
and get it down to two or three, because the one that does the best
in the lab test is not necessarily the one that does the best in the
disease model."
"Good cancer targets are involved in signaling and good antibodies
interrupt the signaling process, which may be more important than
killing the cell," says Drakeman. "So we when we look for
a target, we have a list of what we want the cell to do. We spend
a huge amount of time after we make an antibody, going down the checklist,
to see if it does what we want it to do — to interrupt the signaling
and signal the white blood cells."
"Then, in the lab, we take the cell line, grow up a breast cancer
cell, put our antibody in, and see if it kills the cancer cell."
The only real competitor to Genmab or Medarex is California-based
Abgenix, which put up a stiff fight over the patents that were bought
for Medarex early on. The patents had been filed but had not yet been
issued, and they were so broad that Abgenix had to pay $40 million
to Medarex to even access its own technology. Now anyone wanting to
use human antibodies produced by genetically engineered mice has to
pay licensing fees to Medarex. Some competition is offered by companies
that make antibodies that are 90 percent human, under the assumption
that most patients will tolerate that percentage.
Lisa Drakeman says that, compared to antibodies made in other ways,
GenMab’s antibodies are at least 100 times better at getting where
they are supposed to go and staying there, and that they send better
signals. "We can use a fraction of the amount of material with
better results. If you are a patient, that is what you want to hear,
that killing more cancer cells with less medicine is a real possibility."
The previous methods for producing an antibody involved genetically
modifying the antibody to be acceptable to humans after the mouse
produced it. The only two therapies approved so far by the FDA were
devised with the old method, without benefit of the genetically engineered
mouse. Genentech holds the patent on Herceptin, a therapy for breast
cancer, and IDEC produces Retuxin, used for lymphoma.
The next win could be Genmab’s. It has a three-way collaboration with
Medarex and Oxford Glyco Sciences to work on breast cancer programs.
Drakeman is justifiably proud of how quickly and efficiently she has
built her young company. Founded three years ago, Genmab is the fifth
largest biotechnology company in Europe, and it is among the top 40
in the more crowded biotech space of the United States. "We have
a lot of cash, good infrastructure, and products in development,"
she says. "By year end, we will be the best funded, based on burn
rate."
"Where we distinguish ourselves is the ability to move things
forward. We are the youngest of the transgenic mouse companies, but
we are the only one in Phase III clinical trials with an antibody
from a transgenic mouse," she says. "It’s a team thing. We
work unusually well together. I consider our clinical development
and preclinical development teams to be the best in the industry.
We moved quickly, from Phase I to III in less than 2 1/2 years. My
job is to set goals and keep the team together."
But at least some of Genmab’s success can be traced to its inheritance
from Medarex. At its founding Genmab gave Medarex 31 percent of the
stock in exchange for 16 fee-free licenses to develop products using
Medarex’ genetically engineered mouse.
"What’s good for Genmab is good for Medarex because Medarex is
a shareholder, and we are helping to spread the technology," she
says. Medarex and Genmab are not in direct competition for the same
disease target, but as Drakeman points out, "there is competition
everywhere. One of the things that it is my job to do is to see that
Genmab gets the attention. Investors ask me all the time, `Why is
Genmab different?’"
Explaining the difference between the two companies, Drakeman says
that though Medarex does do some work on products, it focuses more
on licensing out its very valuable technology — the mice that
produce human antibodies. Medarex has an impeccable patent position,
so any company working with mouse-produced antibodies must pay licensing
fees.
In contrast, Genmab intensely focuses on product development and has
used five of its Medarex licenses. That it already has a broader pipeline
than Medarex is partly due to a very successful stock offering in
Copenhagen. "We raised a ton of money very rapidly in Europe,"
says Drakeman. "We are one of a small handful of product companies
in Europe, and we had a real window of opportunity. In Europe, it
is easier to get the attention of people who would be financing biotech
companies if you have a good company and a good plan."
Now Lisa Drakeman lives a bi-continental life, spending
an approximately equal amount of time on both sides of the Atlantic.
She has an apartment in Copenhagen, where Genmab has a 75-person headquarters;
a favorite hotel in Utrecht, the city in the Netherlands where Chief
Scientific Officer Jan G. J. van de Winkel has a 60-person laboratory;
and her office recently occupied the 20,000-foot second floor of 457
North Harrison Street, which will house up to 60 people, most of whom
will manage clinical trials. She sees her husband, Don, as often in
Europe and England as she does at home.
It’s also a high profile life. "Everybody in Europe knows who
I am. As far as I know I am the only women CEO of a public biotech
in Europe and there are only a handful of them in the United States,"
she says. The "good old boy" network operates less effectively
in biotech, which is a young industry. "You don’t have a group
of people who are all men, ahead of you." And in biotech, results
are what count, regardless of gender. "Because it is an entrepreneurial
industry, in some ways, it may be a little easier for women."
Lisa Drakeman grew up in New Hampshire, where her father was a forest
ranger. When the family moved to Pennsylvania, her mother, Jo Natale,
studied gemology and founded a jewelry store where her father and
one sister now work. Of the other two younger sisters, one is a psychiatrist
and the other a microbiologist.
She met her husband when both were college freshmen — she at Mount
Holyoke, he at Dartmouth, and they graduated in 1975. She worked at
the U.S. Treasury while her husband went to law school, and then they
moved to New Jersey, where she earned a master’s degree at Rutgers.
Both the Drakemans earned PhDs in religious history at Princeton University
and taught classes in the department. Their two daughters were born
during this period. One is now a graduate student in classical archaeology
at Oxford and the other is a sophomore at Haverford.
"Imagine going to graduate school with two preschoolers,"
she remembers. "When did I study? After they went to bed. I was
working pretty late. But it was important for me to finish my doctorate,
and I wasn’t leaving without it. I saw the women ahead of me not finish.
I was the only women in the decade of the ’80s to get a PhD in my
department. And the job market was tough. I certainly thought when
I was in graduate school that I would look for academic jobs but the
Medarex opportunity came up first."
She began working full-time at Medarex when the second of their two
daughters began grade school. "I honestly think that I was very
fortunate in my business experience. I reported to Mike Applebaum
(former CFO, now retired). There was a lot I could learn from all
the people I worked with and Don is on that list too. I had a nice
working relationship with people who were happy I was there. Not everybody
gets that opportunity."
While at Medarex, she was named "Advocate of the Year" by
the national Biotechnology Industry Organization. She established
corporate partnerships, managed clinical trials, and developed government
programs for financing biotechnology research.
Genmab’s North Harrison Street site is not a laboratory and no animal
testing goes on here, but mice are indeed used in Utrecht to produce
the human antibodies. What does Lisa Drakeman say to those who protest
the use of any animal, even rodents, other than the obvious reply
about how humanely they are treated?
"I say to people that in a perfect world we wouldn’t need to use
animals to develop new products, but if your choice is your wife with
breast cancer or the mouse, you would choose to develop the product
to treat your wife."
"Because there are antibodies on the market, people are getting
treatment they never had before. People are starting to realize there
is a business here, new medicine that is better than the old."
Only a few mice are used for the early tests, and at later stages
the antibodies are manufactured in a bioreactor. For now Genmab uses
contract manufacturers but has plans to buy its own. "Few biotechs
have made it to commercialization — which I will call success,"
she says. "But three years from now we hope to be profitable."
08540. Lisa Drakeman, CEO. 609-430-2481; fax, 609-430-2482. Www.genmab.com
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