Press Releases

Plexxikon Treats Initial Patient With First-in-Class Drug in Phase 1 Trial

Berkeley, CA - October 8, 2009

Plexxikon Inc. today announced that dosing of cancer patients with PLX3397 has started in a Phase 1 clinical trial. PLX3397 is a novel, oral investigational drug for treating multiple diseases, including metastatic cancer and rheumatoid arthritis. PLX3397 is a highly selective kinase inhibitor that down-modulates macrophages, osteoclasts and mast cells—all cells derived from the immune system—as well as certain tumor cells that promote tumor growth and metastases to the bone. By targeting these cells and consequently, certain cytokines, PLX3397 has been shown to be effective in reducing circulating tumor burden, bone erosion and pain associated with such erosion, in preclinical cancer models. Similarly, PLX3397 has demonstrated reduced inflammation and joint disease in several models of inflammation and autoimmune disease. PLX3397 is the first drug candidate in Plexxikon’s portfolio of compounds targeting these cell types that should enable the company to develop differentiated drugs for treatment of a wide range of diseases. Plexxikon expects to advance a second drug candidate from this portfolio to the clinic in 2010 to more specifically address other disease indications.

The Phase 1 study is a dose escalation trial, which will enroll up to 50 patients with certain cancers, including metastatic disease. Patients with solid tumors will receive PLX3397 orally in cycles of 28 days. The primary objective of this trial is to assess the safety, tolerability and pharmacokinetic profile of PLX3397. An additional follow-on Phase 1b study is planned in patients with rheumatoid arthritis. Pending completion of the Phase 1 studies, Plexxikon plans to explore further clinical development potentially both in cancer and rheumatoid arthritis patients. More information about the trial for metastatic disease is available at

“PLX3397 is the sixth IND candidate to be generated by Plexxikon, further validating our platform as a discovery engine. It represents the first molecule among a portfolio of compounds with distinct and rational profiles selective for these targets,” stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “Given the high degree of selectivity of our kinase inhibitors and potential improved safety profile, we may now address a wide range of diseases with significant unmet needs, including cancer and rheumatoid arthritis. In addition, the brain penetrability of PLX3397 potentially makes this an attractive drug for brain cancer and neuro-inflammatory diseases, such as Alzheimer’s Disease and multiple sclerosis.”

Potential for PLX3397 in the Treatment of Metastatic Cancer

PLX3397 is a first-in-class, oral agent which—due to its multiple mechanistic avenues—may have applicability for several immune-mediated diseases. The compound’s high degree of selectivity potentially mitigates safety issues that otherwise may arise as a result of off-target activity. As a potent small molecule, PLX3397 inhibits macrophage migration and proliferation as well as the production of pro-inflammatory cytokines. In addition, PLX3397 prevents osteoclast formation and activation, which could prevent bone destruction, and also inhibits mast cell proliferation, providing another avenue to counteract inflammation. Preclinical data have shown PLX3397’s antitumor effects, including a decrease in circulating tumor burden, delay of tumor metastases and inhibition of tumor growth. Plexxikon is planning to explore PLX3397 in metastatic breast and prostate cancers, gastrointestinal stromal tumors (GIST), melanoma and brain cancer.

Potential for PLX3397 and Portfolio in the Treatment of Autoimmune Diseases

Preclinical data also have shown PLX3397 to be effective in efficacy models of rheumatoid arthritis, multiple sclerosis, lupus nephritis and neurofibromatosis, among others. In these models, the numbers of macrophages, osteoclasts and/or mast cells have been reduced to almost normal levels at the site of inflammation. Disease scores relative to controls have been significantly improved, while bone erosion and pain have been reduced. Kidney function has been improved as a consequence of reduced macrophage infiltration.

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 clinical stage programs include PLX4032 for the treatment of melanoma and colorectal cancer, PLX5568 for the treatment of polycystic kidney disease, PLX204 for the treatment of diabetes and PLX3397 for the treatment of metastatic disease and rheumatoid arthritis. Among the company’s preclinical development programs, candidates are being developed for the treatment of rheumatoid arthritis, 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 one key component that provides a significant competitive advantage over other drug discovery approaches. To date, the company has discovered a portfolio of clinical and preclinical stage compounds being developed to address significant unmet medical needs in cardio-renal disease, CNS disorders, inflammatory and neuro-inflammatory diseases and oncology.