Thursday September 11, 9:00 am ET

SUNNYVALE, Calif., Sept. 11 /PRNewswire-FirstCall/ -- Pharmacyclics, Inc. (Nasdaq: PCYC - News) today announced the presentation of promising findings from preclinical studies of a novel drug candidate to treat neurodegenerative diseases based on its proprietary texaphyrin technology platform. The presentation at the 226th American Chemical Society National meeting being held today in New York provided evidence for the therapeutic effects of metallotexaphyrin molecules for the treatment of the progressive neurodegenerative disease Amylotrophic Lateral Sclerosis (ALS), often referred to as "Lou Gehrig's disease."

"These results are among the best ever seen for late onset administration of any pharmacotherapeutic agent and suggest that administration of such agents at disease onset, roughly equivalent to the earliest time when human treatment could begin, can fundamentally alter the course of the disease," said John Crow, M.S., Ph.D., professor of pharmacology and toxicology, University of Arkansas of Medical Sciences.

The study entitled: "Metallotexaphyrins administered at onset of disease enhance survival and preserve motor function of ALS transgenic mice," presented by Dr. John Crow describes experiments undertaken to evaluate the potential of metallotexaphyrins to affect progressive neurodegeneration in a mouse model of ALS. These mice have a genetic mutation that induces a condition similar to ALS. At the approximate age of 100 days the mice develop hindlimb weakness, which rapidly progresses to total body paralysis within 10- 14 days and ultimately death. Animals receiving a metallotexaphyrin, administered after disease onset, showed a dramatic increase in survival and preservation of neurologic function. These results suggest that administration of such agents, even when delivered at the first sign of overt disease symptoms, can alter the course of disease.

"The unique and versatile biochemical properties of texaphyrins allow for diverse applications in medicine," said Richard A. Miller, M.D., president and chief executive officer of Pharmacyclics. "Our technology platform enables the production of drug candidates with novel properties by making slight modifications of chemical structure. We are focused on the application of our technology in oncology with our lead product Xcytrin®, but other molecules, such as Antrin® in atherosclerosis, continue to show promise in other indications, and we are now excited by the identification of neurodegenerative disease as a potential opportunity for our technology."

About Amylotrophic Lateral Sclerosis

ALS, also known as Lou Gehrig's disease, is a progressive neurodegenerative disease that targets motor neurons, which stretch from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With all voluntary muscle action affected, patients in the later stages of the disease become totally paralyzed, yet in the majority of patients, cognitive function remains unaffected. Most patients with ALS survive less than five years. Recently, animal models for this disease have been developed. These animals have gene mutations that result in overproduction of reactive oxygen species in tissue, which is thought to be involved in the disease process.

Texaphyrins

Texaphyrins are rationally designed synthetic molecules that resemble naturally occurring molecules known as porphyrins. These molecules contain a central metal ion (metallotexaphyrin), which is held tightly in place by a ring-like chemical structure. The properties of texaphyrins can be altered by substitution of various metal ions in the central cavity of the compound. Texaphyrins, like porphyrins, tend to accumulate in areas of disease such as cancer or inflammation. Metallotexaphyrins can be designed with particular chemical properties aimed at altering a disease state or eliminating diseased tissues such as cancer. In the case of ALS, a metallotexaphyrin was designed that would neutralize the toxic reactive oxygen species produced by diseased neurologic tissue.

About Xcytrin

Xcytrin, Pharmacyclics' lead compound, is a texaphyrin. It possesses a novel mechanism of action that allows the tumor targeted generation of intracellular molecules known as reactive oxygen species (ROS). After administration, Xcytrin selectively localizes and accumulates inside cancer cells, due to their high rates of metabolism, including anaerobic glycolysis. Because Xcytrin is a paramagnetic compound, its presence is detectable with magnetic resonance imaging (MRI). Studies with MRI have confirmed the selective localization of Xcytrin in primary and metastatic tumors.

Within cancer cells, Xcytrin disrupts cellular metabolism, interferes with the flow of energy, and results in the generation of ROS. This mechanism of action of Xcytrin is believed to make cancer cells more vulnerable to the oxidative stress (i.e., specific types of damage involving oxidation-reduction reactions) caused by radiation therapy and chemotherapy. The generation of ROS within cancer cells promotes a process called programmed cell death, or apoptosis, leading to the selective destruction of the cancer cells.

Preclinical studies have shown that Xcytrin enhances the efficacy of radiation therapy and that of several commonly used chemotherapy agents. Currently, Xcytrin is being investigated as a potential therapeutic in combination with radiation therapy and/or chemotherapy and as a single agent for various types of cancers in several phase 1 and phase 2 clinical trials sponsored by Pharmacyclics and/or the National Cancer Institute.

About Pharmacyclics

Pharmacyclics is a pharmaceutical company developing products to improve upon current therapeutic approaches to cancer and atherosclerosis. The company's investigational compounds are rationally designed, ring-shaped small molecules called texaphyrins that disrupt the bioenergetic processes of diseased cells, such as cancer and atherosclerotic plaque. When activated by various forms of energy, including X-ray and light, these texaphyrins can help to reduce or eliminate the diseased tissue. More information about the company, its technology, and products in development can be found on its web site at www.pcyc.com.

NOTE: The statements made in this press release about progress of clinical trial results 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, and results of clinical trials, the progress of research and development programs, whether the results of preclinical studies will produce similar results in humans in clinical studies, the regulatory approval process in the U.S. 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 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®, Xcytrin®, Antrin® and the "pentadentate" logo® are registered trademarks of Pharmacyclics, Inc.

Source: Pharmacyclics, Inc.