Pharmacyclics Reports Data Highlighting Novel Mechanism and Diverse Potential Uses of Xcytrin in Cancer, Including Multiple Myeloma

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Pharmacyclics Reports Data Highlighting Novel Mechanism and Diverse Potential Uses of Xcytrin in Cancer, Including Multiple Myeloma
    SUNNYVALE, Calif., April 10 /PRNewswire-FirstCall/ --
Pharmacyclics, Inc. (Nasdaq: PCYC), today reported data demonstrating the
unique mechanism of action and the potential broad utility of Xcytrin(R)
(motexafin gadolinium) in cancer therapy, including as a potential monotherapy
for multiple myeloma.  Six abstracts describing these findings were published
in the 2003 Proceedings of the Annual Meeting of the American Association for
Cancer Research (AACR) and were to be presented by company researchers and
collaborators at Northwestern University and Yale University during the AACR's
recently postponed annual meeting in Toronto, Canada.
    "Xcytrin alone is cytotoxic to cancer cell lines derived from
hematological malignancies," said Richard A. Miller, M.D., president and chief
executive officer of Pharmacyclics.  "Xcytrin selectively localizes in cancer
cells, which have high rates of metabolism.  The ability of Xcytrin to inhibit
cellular respiration results in the generation of reactive oxygen species
(ROS), which can selectively destroy cancer cells via the induction of
programmed cell death (apoptosis).  We are excited about these findings
because myeloma and lymphomas appear to be very sensitive to ROS.  Phase 2
clinical trials of Xcytrin alone and in combination with chemotherapy for
multiple myeloma and lymphomas are planned to begin later this year."

    Abstract Highlights
    An abstract by Andrew Evens, D.O., at Northwestern University and other
researchers at Northwestern and Pharmacyclics indicated that a variety of
steroid-sensitive, steroid-resistant, chemotherapy-sensitive, and
chemotherapy-resistant myeloma cell lines in vitro were very sensitive to the
anti-metabolic and cytotoxic effects of Xcytrin monotherapy.  The myeloma
cells treated with Xcytrin exhibited significant uptake of the drug,
physiologic changes characteristic of inhibition of metabolism and alterations
in redox pathways resulting in generation of ROS.  These effects led to
cellular changes characteristic of apoptosis and reduced cell survival
(viability).
    According to Dr. Evens, "Xcytrin may be a new, targeted therapy for
multiple myeloma and other hematological malignancies.  Xcytrin represents a
novel agent that is believed to work through a unique mechanism of action
involving futile redox cycling, a process that disrupts cellular metabolism
and generates reactive oxygen species, an important cellular signal for
apoptosis or programmed cell death.  Our study is the first demonstration of
the activity of Xcytrin in cells derived from hematopoietic malignancies.  The
selective uptake and potency of Xcytrin when used as monotherapy in myeloma
cell lines, including those resistant to standard chemotherapeutics and other
antineoplastic agents, were impressive, and warrant exploration in clinical
trials."
    Abstracts by Erling Donnelley, M.D. and Sara Rockwell, M.D., at Yale
University, and colleagues at Yale and Pharmacyclics described the effects of
Xcytrin on metabolism and oxygen consumption in cancer cells.  Xcytrin
inhibited oxygen consumption by blocking metabolism in both cultured EMT6
cells (mouse mammary tumor cells) and human lymphoma cells. Furthermore,
Xcytrin Injection (IV) selectively inhibited oxygen utilization in xenografts
of A549 (human lung cancer) cells and implants of EMT6 in mice, whereas blood
flow to the A549 tumors appeared unchanged.  These findings demonstrate that
Xcytrin inhibits metabolism and decreases oxygen consumption as the cancer
cells lose viability.
    In another abstract on Xcytrin, in combination with various
chemotherapeutic drugs, Darren Magda, Ph.D., and other scientists at
Pharmacyclics demonstrated that Xcytrin enhanced the cytotoxic activity of the
chemotherapy agents, docetaxel, paclitaxel, methotrexate, and 5-fluorouracil
in cultured cells in vitro from various solid tumors and in vivo in animal
models.

    About Xcytrin
    Xcytrin is the first of a new class of drugs called texaphyrins, which
selectively accumulate in cancer and other diseased cells based on their
unique biochemical features, and disrupt cellular metabolism.  Xcytrin
generates ROS in cells by disrupting the flow of energy.  Xcytrin prevents
cancer cells from repairing damage caused by the effects of radiation and
chemotherapy without increasing damage to normal tissue.  Xcytrin is
paramagnetic, and when localized in cancer cells, produces an enhancement of
the MRI signal, which can be used to image the tumor.
    Pharmacyclics is developing Xcytrin Injection for a variety of therapeutic
applications in oncology.  Xcytrin Injection in combination with radiotherapy
is undergoing a pivotal Phase 3 clinical trial for potential treatment of lung
cancer patients with brain metastases (i.e., lung cancer that has spread to
the brain) and Phase 2 trials in patients with primary brain tumors.  Phase 1
trials of the combination of Xcytrin Injection, radiation therapy, and
chemotherapy for lung cancer patients and head and neck cancer patients are in
progress.  Also ongoing are Phase 1 trials of Xcytrin Injection in combination
with chemotherapy in patients with advanced malignancies.

    About Pharmacyclics
    Pharmacyclics is a pharmaceutical company developing products to improve
upon current therapeutic approaches to cancer and atherosclerosis.  The
company's products are rationally designed, ring-shaped small molecules called
texaphyrins that selectively target and disrupt the bioenergetic processes of
diseased cells, such as cancer and atherosclerotic plaque.  More information
about the company, its technology, and products can be found on its web site
at http://www.pcyc.com.

    NOTE:  The statements made in this press release about progress and
reports of results from preclinical studies, clinical trial results, clinical
development plans, and product development activities other than statements of
historical fact, are forward-looking statements.  The forward-looking
statements are subject to risks and uncertainties that may cause actual
results to differ materially from those in the forward-looking statements,
including risks associated with the initiation, timing, design, enrollment,
and cost of clinical trials; the progress of research and development
programs; the regulatory approval process in the United States and other
countries; and future capital requirements.  For further information about
risks that may affect the actual results achieved by Pharmacyclics, please see
the company's reports as filed with the U.S. Securities and Exchange
Commission from time to time, including but not limited to, its reports on
Forms 10-Q and 10-K. Pharmacyclics(R), the "pentadentate" logo(R) and
Xcytrin(R) are registered trademarks of Pharmacyclics, Inc.
SOURCE Pharmacyclics, Inc.
http://www.pcyc.com
CONTACT:
Jim Weiss or Leiv Lea, both of Pharmacyclics,
Inc., +1-408-774-0330, or cell, +1-415-203-0328