Press Releases

Plexxikon’s PLX3397 Preclinical Data Demonstrate Potential of Novel, “First-in-Class” Cancer Drug

Phase 1 Clinical Trial Under Way in Patients with Metastatic Cancers

BERKELEY, Calif. and WASHINGTON, DC – April 20, 2010

Plexxikon Inc. today announced promising preclinical data from in vivo cancer studies with PLX3397 demonstrating significant reduction in tumor burden, metastatic spread, bone erosion and cancer bone pain. PLX3397 is an oral, selective kinase inhibitor that down-modulates macrophages, microglia, osteoclasts and mast cells, all cell types targeted by this drug candidate. These cell types play a key role in cancer and metastasis. These data were presented today at the American Association for Cancer Research Annual Meeting in Washington DC. PLX3397 is currently being evaluated in a Phase 1 clinical trial for metastatic solid tumors.

In preclinical studies, PLX3397 treatment resulted in the following anti-cancer effects:
• Circulating tumor cells reduced
Circulating tumor cells (CTCs) were strikingly reduced within 24 hours following PLX3397 treatment compared to vehicle. Recent literature shows that therapies that reduce CTCs improve patient survival.
• Primary tumors and metastases reduced
PLX3397 treatment in a bone cancer model resulted in reduced tumor volume and invasion compared to the untreated cohort.
• Normal bone volumes maintained
PLX3397 treatment was shown to preserve normal bone volumes compared to significant bone destruction due to osteolytic cancer growth in the untreated cohort.
• Cancer-associated pain reduced
Pain levels were normalized with PLX3397 treatment compared with the untreated cohort.
• Cancer-related bone fractures prevented
No fractures were seen with PLX3397 treatment, whereas 100 percent of the untreated cohort experienced metastasis-related fractures.
• Primary tumors inhibited with combination treatment
A combination study with PLX3397 treatment and Taxol, a chemotherapeutic agent, showed a significant, synergistic anti-tumor effect in a breast cancer model.

“PLX3397 is an important component of Plexxikon’s growing oncology franchise, as well as the lead candidate from our portfolio of highly selective Fms kinase inhibitors. We are excited about the potential to target mechanisms that drive disease progression, metastatic disease and bone pain experienced by cancer patients,” stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “Early, but promising bio-response data from our Phase 1 trial has shown activity consistent with the preclinical data reported today. PLX3397 could represent an important first-in-class cancer treatment.”

Rationale for PLX3397 as Treatment for Metastatic Cancers
PLX3397 selectively targets a number of cell types, including macrophages, microglia, osteoclasts and mast cells. These cells are involved in various aspects of tumor growth and metastasis. Growth factors for these cells are elevated in significant subsets of different human cancers (breast, colorectal, lung , glioblastoma, prostate cancers). These growth factors consequently activate these target cells leading to a microenvironment that supports tumor growth and also enables the tumor cells to escape into the blood stream and form metastases to distant sites, particularly to bone. Metastases to the bone can cause significant pain.

Phase 1 Clinical Trial for PLX3397 Currently Enrolling Patients
The Phase 1 study is a dose escalation trial, which is enrolling up to 50 patients with selected metastatic cancers. Patients with solid tumors are receiving PLX3397 orally in cycles of 28 days. The primary objective of this trial is to assess the safety, tolerability and pharmacokinetic profile of PLX3397. Additionally, a number of bio-response markers are being measured, including circulating tumor cells.

Upon completion of dose escalation and selection of the maximum tolerated dose, Plexxikon plans to explore potential efficacy in a proof-of-concept trial, specifically in metastatic breast cancer. More information about the Phase 1 trial is available at

Potential for PLX3397 in the Treatment of Autoimmune Diseases
Preclinical data also have shown PLX3397 to be effective and disease-modifying in models of rheumatoid arthritis, multiple sclerosis, and lupus, among others. In these models, the numbers of macrophages, osteoclasts and/or mast cells have been reduced to near normal levels at the site of inflammation. Disease scores relative to controls have been significantly improved, while bone erosion has been reduced or bone restored and pain has been reduced. An additional Phase 1b study is planned in patients with rheumatoid arthritis, targeted to initiate enrollment in Q2 2010.

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 and rheumatoid arthritis. Among the company’s preclinical development 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 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.