Abbott Researchers Focus On New Cutting-Edge Approaches In The Fight Against Cancer

For decades,
scientists have looked for new therapies that target cancer. Researchers
now know that cancer cells have several unique characteristics -- they
require new blood vessels to deliver oxygen and nutrients (angiogenesis),
they grow uncontrollably (proliferation), they travel throughout the body
(metastasis), and they escape programmed cell death, a natural process by
which the body rids itself of damaged or unwanted cells (apoptosis). Robust
preclinical data shows that several compounds in Abbott's oncology pipeline
interfere with these vital processes. Data on two of these compounds will
be presented at the American Association for Cancer Research (AACR) Annual
Meeting being held April 14-18 in Los Angeles.



During the meeting, scientists from independent academic institutions
and Abbott will present data on Abbott's Bcl-2 family protein inhibitor
(ABT-263). This compound, currently in early clinical development, corrects
defects in cancer cells that allow them to escape programmed cell death.
They will also present data on an investigational PARP inhibitor (ABT-888)
that enhances the effectiveness of common cancer therapies that damage DNA
in cancer cells.



Presentation highlights include:


ABT-263


-- "ABT-263: An orally bioavailable Bcl-2 family protein inhibitor"
[Oral presentation, Sunday, April 15, 1 p.m., Hall A]


-- "Pediatric preclinical testing program (PPTP) evaluation of the Bcl-2
inhibitor ABT-263"
[Oral presentation, Tuesday, April 17, 3:55 p.m., Room 404 A-B]



ABT-888


-- "The poly(ADP-ribose) polymerase (PARP) inhibitor, ABT-888 potentiates
the antitumor activity of temozolomide in the B16F10 syngeneic
melanoma model: Correlation with pharmacokinetic levels and a
reduction in poly(ADP-ribose) polymer by ELISA"
[Oral presentation, Tuesday, April 17, 2:40 p.m., Room 404 A-B]


-- "ABT-888, a potent PARP inhibitor, enhances the antitumor activities
by a variety of chemotherapeutic agents in vivo"
[Poster session, Abstract #1457, Sunday, April 15, 1 p.m. - 5 p.m.,
Poster section 28, Poster 14, Exhibit Hall]


"Cancer accounts for nearly 25 percent of all deaths in the United
States, second only to heart disease," said Stephen Fesik, Ph.D.,
divisional vice president, Cancer Research, Abbott. "Abbott's Oncology
Discovery team is dedicated to finding the next generation of small
molecule and biologic therapies that will have an impact on this horrible
disease."



"There is particular excitement from the scientific community
surrounding Abbott's Bcl-2 family protein inhibitors which block the action
of a class of proteins that regulate apoptosis," said Fesik. "This
ground-breaking program may prove to be extremely valuable in the fight
against cancer. In fact, dozens of researchers from around the world are
studying Abbott's Bcl-2 family protein inhibitors and will reveal some of
their results at this meeting."
















Background on Abbott's Oncology Pipeline



Bcl-2 Family Protein Inhibitors (ABT-263)



Researchers have been interested in the Bcl-2 family of proteins since
their role in preventing apoptosis -- the natural process by which damaged
or unwanted cells die and are cleared from the body -- was proven more than
a decade ago. Discovered by Abbott scientists, ABT-263 restores programmed
cell death, a natural mechanism for the elimination of cancerous cells, by
inhibiting the function of Bcl-2 proteins.



Bcl-2 proteins play a central role in regulating apoptosis, as well as
tumor formation, tumor growth and resistance to treatment. Pioneering work
in structural biology at Abbott established how the Bcl-2 family of
proteins interact with one another, leading researchers to develop a novel
compound that causes cancer cells to self-destruct.



ABT-263 recently entered Phase I clinical trials for lymphomas and
solid tumors, including small cell lung cancer. Preclinical data has shown
that Abbott's Bcl-2 family protein inhibitors bind to Bcl-2 proteins,
restoring cell death to cancerous cells. Additionally, the compounds were
found to enhance the effects of chemotherapy and radiation used to treat
other types of cancer, such as non-small cell lung cancer.



PARP Inhibitors (ABT-888)



DNA damaging agents remain some of the most successful treatments for
cancer. The enzyme Poly(ADP-ribose)polymerase (abbreviated PARP) can help
repair DNA damage caused by these agents used to treat cancer and render
them ineffective. As PARP activity is often increased in cancer cells, it
provides these cells with a survival mechanism.



ABT-888 is an oral PARP-inhibitor developed by Abbott researchers to
prevent DNA repair in cancer cells and increase the effectiveness of common
cancer therapies such as radiation and alkylating agents.



ABT-888 has entered a Phase 0 trial for patients with refractory solid
tumors and lymphoid malignancies, and will enter Phase I trials for
melanoma this year. Preclinical data indicates ABT-888 has improved the
effectiveness of radiation and many types of chemotherapy in animal models
of cancer.



Kinase Inhibitors (ABT-869)



Many oncology researchers are currently developing agents that target
kinases, a class of enzymes that are often overly activated in cancer
cells. Inhibition of the appropriate kinases can suppress tumor growth by
cutting off its blood supply.



Discovered by Abbott scientists, ABT-869 is a multitargeted kinase
inhibitor that is in Phase I clinical trials for solid tumors and selected
hematologic malignancies such as leukemia. Phase II trials for several
tumor types will also begin this year. Data presented at previous AACR
meetings highlighted the antitumor effects of ABT-869 across a broad range
of tumor models.



Other Compounds



Abbott scientists remain dedicated to exploring a variety of
cutting-edge treatments in the fight against cancer. In addition to Bcl-2
family protein inhibitors, PARP inhibitors and kinase inhibitors, other
compounds moving through the development pipeline include ABT-751, an oral,
once-daily antimitotic (a class of drugs that inhibit cell division) in
ongoing studies for non-small cell lung cancer, and ABT-828, a biologic
compound that blocks angiogenesis of cancer cells.



About Abbott Oncology



Abbott Oncology is committed to the discovery and development of
innovative cancer treatments that enable patients to live longer and
healthier lives. Abbott's oncology research is focused on developing more
targeted, less toxic therapies than are currently available to improve the
quality of life for some patients living with cancer.



About Abbott



Abbott (NYSE: ABT) is a global, broad-based health care company devoted
to the discovery, development, manufacture and marketing of pharmaceuticals
and medical products, including nutritionals, devices and diagnostics. The
company employs 65,000 people and markets its products in more than 130
countries.




Abbott's news releases and other information are available on the
company's Web site at abbott.


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