Press Releases

Plexxikon's Novel Agent Significantly Inhibits Activation of Key CNS Cells Associated With Alzheimer's Disease

BERKELEY, Calif. and HONOLULU, Hawaii – July 14, 2010

Plexxikon Inc. today announced promising preclinical data from in vivo Alzheimer’s Disease studies demonstrating a dramatic reduction in activated microglia in the brains of very old (22 months) 3xTG-AD mice, a triple transgenic model for Alzheimer’s Disease. This reduction of activated microglia led to significantly improved learning in the treated group. PLX3397 is an oral, brain-permeable, potent and selective inhibitor of a kinase target associated with Macrophage Colony Stimulating Factor (CSF-1), a cytokine which is necessary for the activation of microglia and proliferation of macrophages. These cells play key roles in inflammation and cancer. These data were presented yesterday at the Alzheimer’s Association International Conference on Alzheimer’s Disease in Honolulu, Hawaii. PLX3397 is currently being evaluated in a Phase 1 clinical trial in cancer patients.

In preclinical studies, PLX3397 treatment resulted in the following anti-Alzheimer’s Disease effects:

• Effective penetration of the blood-brain barrier
PLX3397 successfully crossed the blood brain barrier, with oral administration, enabling the kinase inhibitor to block the targeted kinase.

• Dramatic reduction of activated microglia in Alzheimer’s Disease model
Activation of microglial cells was effectively prevented due to PLX3397’s inhibition of the targeted kinase leading to a reduction in the number of activated microglia in the brain, while no effect on disease plaques was observed. Activated microglia appear in elevated numbers associated closely with the disease plaques present in brains of Alzheimer's patients, and are considered by some researchers to play a destructive role in the progression of disease, including neuronal loss and function.

• Unprecedented learning performance
After three months of treatment, the PLX3397-treated group in the Tg3x AD model in very old mice (22 months) demonstrated significantly improved learning performance compared to the untreated group, using the Morris Water Maze for the evaluation of learning and memory.

“PLX3397 has demonstrated the ability to cross the blood-brain barrier which presents a unique opportunity to treat diseases driven by the activation of microglia, such as Alzheimer’s Disease, multiple sclerosis, glioblastoma and possibly other brain tumors,” stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “PLX3397’s selective targeting of the microglia, macrophages and osteoclasts has shown broad utility in a wide range of disease models, where activation or proliferation of these cell types is a key culprit. Plexxikon is developing a portfolio of these selective candidates, each with differentiating features, in order to specifically address not only Alzheimer’s Disease, but also rheumatoid arthritis, multiple sclerosis and many cancers, such as metastatic breast cancer, glioblastoma and Hodgkin’s lymphoma.”

Rationale for PLX3397 as Treatment for Inflammatory Disorders and Cancer
PLX3397 selectively targets a number of cell types, including microglia, macrophages, osteoclasts and mast cells, cells that play key roles in the disease processes in various inflammatory disorders and cancers. Preclinical data have shown PLX3397 to be effective and disease-modifying in models of Alzheimer’s Disease, cancer, rheumatoid arthritis, multiple sclerosis and lupus, among others. Macrophage colony stimulating factor 1 (CSF-1) controls an important signaling pathway in the activation of microglia, and offers a potential therapeutic target to treat neuro-inflammatory conditions including Alzheimer’s Disease.

PLX3397 is already in early clinical trials in cancer patients. The company plans to evaluate PLX3397 in a number of cancers, where the activation or proliferation of the microglia and macrophage contribute to the invasiveness or metastatic spread of the tumor, including metastatic breast cancer, glioblastoma and Hodgkin’s lymphoma. Data from the Phase 1 trial to date, indicate that PLX3397 is well tolerated, and has a half-life of about fifteen hours. Blood levels of PLX3397 have reached the targeted efficacy range with once daily dosing. More information about the Phase 1 trial that is currently enrolling patients with various types of metastatic cancer is available at

About Alzheimer’s Disease
Alzheimer’s Disease is a progressive brain disorder that gradually affects one’s memory as well as one’s abilities to learn, reason, communicate and function in society. More than five million people in the United States are currently living with Alzheimer’s Disease, for which there is currently no cure.

About Plexxikon
Plexxikon is a leader in the structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company’s lead compound, PLX4032, is in late-stage clinical trials for the treatment of melanoma. Other clinical-stage programs include PLX5568 for the treatment of polycystic kidney disease, PLX204 for the treatment of diabetes, and PLX3397 for the treatment of metastatic cancer. Among the company’s preclinical programs, candidates are being developed for the treatment of neuro-inflammatory disorders, multiple sclerosis and other autoimmune diseases as well as for the treatment of other cancers.

Plexxikon’s proprietary Scaffold-Based Drug Discovery™ platform integrates multiple state-of-the-art technologies, including structural screening as a key component that provides a significant competitive advantage over other drug discovery approaches. The company’s portfolio of clinical and preclinical stage compounds address significant unmet medical needs in cardio-renal disease, CNS disorders, inflammatory and neuro-inflammatory diseases, and oncology.