Plexxikon presents promising preclinical data from PLX3397 in vivo cancer studies

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.

“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”

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.