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By controlling a chemical signaling system that repels the
body’s immune system cells, a new member company in Georgia
Tech’s Advanced Technology Development Center (ATDC) hopes
to open up new therapeutic avenues for forms of cancer, autoimmune
disorders and inflammatory diseases.
Using the results of research performed by
Dr.
Mark Poznansky and his team at
Massachusetts
General Hospital and Harvard Medical School in Boston,
Celtaxsys Inc. is developing and testing new drug compounds
designed to block the protective mechanisms created by certain
tumors to prevent attack by immune system cells. The early-stage
company is also working on drugs that would address the opposite
effect, treating inflammatory and autoimmune disorders by
moving the cells away from locations where they’re not needed.
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Certain cancers use fugetaxis to
repel immune system cells (top). Celtaxsys is developing
anti-fugetaxis drugs that will block that process (bottom),
allowing immune cells to attack the cancer. |
“Depending on the disease, our compounds would either eliminate
cells from an environment or allow cells into an environment,”
explains Bill Reddick, the company’s president. “For instance,
many forms of cancer build what is essentially a moat around
the tumor that prevents immune system cells from entering.
We are building a bridge across the moat to allow the body’s
defensive mechanisms to attack the cancer.”
In scientific terms, the company hopes to control a newly-discovered
cell migration pathway known as fugetaxis, which depends on
the action of specific proteins. A two-pronged goal would
be (1) to develop pharmaceutical compounds that would block
the activity of the protein for treating cancer – and (2)
launch the mechanism for treating inflammatory or autoimmune
disorders.
By blocking the tumor’s protective mechanisms, the Celtaxsys
compounds would allow the body’s immune system to do its job
– which should produce fewer side effects than existing chemotherapy
agents.
“The beauty of this from a therapeutic perspective is that
our compound doesn’t kill healthy cells,” Reddick explains.
“It will disable the defense mechanism for a period of time,
but by itself doesn’t kill any cells. You would expect the
toxicity of our drugs to be far less than traditional chemotherapy.”
Animal testing shows that antifugetactic compounds can inhibit
the protective mechanism of cancers, allowing immune system
T-cells to enter tumors on mice. Once inside, the T-cells
recognize, attack and destroy cancer cells.
“For some time there has been data suggesting that the presence
of T-cells in certain tumors was an indication of how the
disease would progress,” Reddick says. “If a tumor biopsy
demonstrates high levels of T-cells, that suggests the disease
will progress more slowly than if there are no T-cells in
the tumor. So if we can allow T-cells to infiltrate certain
tumors, we would expect to have an impact on tumor progression.”
Many malignancies – including malignant melanoma and ovarian
cancer – use similar defense mechanisms to hold back the body’s
immune system, though different compounds may be required
to block the process in each type of cancer, Reddick says.
The compounds the company is screening for the other side
of the scenario – repelling immune system cells to reduce
inflammation and autoimmune disorders – would have similar
advantages. There, the compounds would simply repel the cells
away from discrete locations – such as the joints in the case
of rheumatoid arthritis. The process of repulsion does not
harm the immune cells.
“We have identified a novel mechanism that until recently
was unknown,” he adds. “The potential applications are wide
ranging.”
From its laboratory space in the
ATDC
Biosciences Center, Celtaxsys is screening potential drug
compounds for both fugetactic and antifugetactic effects.
Promising compounds would be tested in animals before the
company could seek approval for human testing.
“We will soon have novel compounds that cause this process
to happen, or alternatively, cause it to stop happening,”
Reddick says. “We can envision a pathway through which we
could begin human trials as early as 2007.”
The company has so far raised $5.7 million in angel funding
through
Caymus Partners.
The funding is supported by nearly a dozen patents and patent
applications – and an internationally-known scientific advisory
board that includes such luminaries as Dr.
Judah
Folkman of Harvard Medical School, Dr. John Potts of Massachusetts
General Hospital, and Dr.
Nicolas Chronos of the
American
Cardiovascular Research Institute.
In addition to Reddick, the company’s management team includes
Dr. Mark Poznansky of Harvard Medical School, scientific founder
and scientific advisory board chairman; Ralph Grosswald, director
of operations; and Hyun Kang Ph.D, senior scientist. The company
also operates with a board of directors that includes Chronos;
Potts; Joseph Davie, former head of research for Biogen; Matthew
Dontzin, managing partner of the Dontzin Law Firm; and Michael
Masters, founder of Masters Capital.
Because of its Boston roots, Celtaxsys considered launching
its operations there. But because three of its founders are
from Atlanta – and because the city could offer a supportive
environment – the startup came to ATDC, which offered laboratory
space.
“When you start a biotechnology company, you have a fairly
imposing list of things to do,” Reddick says. “The ability
to open a first-class lab facility as a turnkey operation
is a tremendous benefit. There is no way that we could have
gotten that done by ourselves in just two-and-a-half months.”
Another ATDC advantage is being part of community that includes
entrepreneurs who have already traveled the path Celtaxsys
has begun, he added.
The company’s location in Atlanta has allowed it to hire
skilled technical personnel, and to begin interactions with
researchers at the Georgia Institute of Technology, Emory
University and the University of Georgia. “We anticipate a
lot of local partnerships,” Reddick says.
As it develops promising therapeutic compounds, Celtaxsys
plans to brings its products to market by building partnerships
with pharmaceutical companies that already have extensive
manufacturing, distribution and sales channels.
“We don’t feel that there is a need for additional fully-integrated
drug companies,” Reddick explains. “Our strength is in drug
discovery, so we intend to focus on developing novel therapeutics
and then partnering with more fully integrated companies.”
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