Plexxikon Inc. announced positive data from an interim analysis of the BRIM3 trial, a large multi-center Phase 3 clinical study of PLX4032 (RG7204) in patients with previously untreated metastatic melanoma with the BRAF mutation. Patients treated with PLX4032 had an improved overall survival (OS) compared to patients treated with dacarbazine, the current standard of care. In addition, these patients lived longer on average without their disease getting worse, as measured by progression-free survival (PFS). PLX4032 is an oral, novel kinase inhibitor that targets the oncogenic BRAF mutation.

The BRIM3 analysis showed that the study met the pre-specified criteria for co-primary endpoints of OS and PFS. The safety profile was generally consistent with the previous PLX4032 studies. Based on these results, patients on the dacarbazine arm of the study will have the option to crossover to receive PLX4032. Additionally, the Expanded Access Program also will now be opened to previously untreated melanoma patients with the BRAF mutation. Comprehensive clinical data from the BRIM3 trial are expected to be presented at a major medical meeting later this year.

"This positive effect on overall survival represents a significant development for melanoma patients," said K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. "As a novel, first-in class, personalized medicine, together with its companion diagnostic, PLX4032 sets the stage for a strong foundation for Plexxikon's commercial franchise in oncology. PLX4032, first tested in patients in 2006, demonstrates the potential to accelerate development when appropriate patients can be selected with a diagnostic and treated with a targeted medicine."

Recently, Plexxikon announced its agreement to co-promote PLX4032 in the U.S. with Genentech, and is planning to begin building its commercial organization and sales force this year. PLX4032 is being co-developed with Roche, and now Genentech, a member of the Roche Group, under a 2006 license and collaboration agreement between Plexxikon and Roche. The companies plan to file for marketing approval with the health authorities in the U.S. and in Europe for PLX4032, and for its companion diagnostic, in 2011.

Combination trials with PLX4032, as well as trials in other BRAF-mutated cancers, are also planned.

In other recent news, the U.S. Patent and Trademark Office issued Plexxikon's U.S. Patent No. 7,863,288, covering composition-of-matter claims for PLX4032 and providing a patent term until 2029. The accelerated development of a personalized medicine such as PLX4032 not only provides patient access to new medicines more quickly, but also maximizes patent life, thereby contributing substantive value to the program. The new U.S. patent further broadens Plexxikon's intellectual property portfolio.

About BRIM3

BRIM3 is a global, randomized, open-label, controlled, multicenter Phase 3 study evaluating PLX4032 compared to dacarbazine (the current chemotherapy standard of care) in patients with previously untreated mutation-positive metastatic melanoma.

Study participants were randomized to receive either: PLX4032 960 mg orally twice daily, or dacarbazine 1000 mg/m2 intravenously every three weeks. Patients continue dosing until their disease progresses or there is unacceptable toxicity. Enrollment is completed, with 675 patients enrolled in this study. BRIM3 was initiated in December 2009 and included over 100 sites worldwide.

About Melanoma

Melanoma is the most serious type of skin cancer and is growing at a rate of about five to six percent annually. More than 70,000 people in the U.S. and 160,000 people worldwide are diagnosed with melanoma each year. It is one of the deadliest cancers, with a five-year survival rate of 15 percent for people with advanced (Stage IV) melanoma, according to the American Cancer Society.

Risk factors for melanoma include a positive family history of melanoma, prior melanoma, multiple clinically atypical moles or dysplastic nevi, inherited genetic mutations, fair skin and sun exposure. However, melanoma can occur in any ethnic group and also in areas of the body without substantial exposure to the sun.

About PLX4032 (RG7204)-A Personalized Medicine for Cancer Treatment

PLX4032 is a novel, oral small molecule for treating melanoma and other cancers harboring the oncogenic BRAF mutation. Plexxikon utilized its structure-guided chemistry platform to discover PLX4032, and initiated clinical development in 2006. A DNA-based companion diagnostic to identify patients whose tumors carry the BRAF mutation is being co-developed by Plexxikon and Roche Molecular Diagnostics in parallel with the therapeutic development of PLX4032.

A Phase 2 clinical trial of previously treated metastatic melanoma patients showed a 52 percent response rate, and tumor shrinkage in the majority of patients, consistent with results from earlier studies. The most common drug-related adverse events were rash, photosensitivity, hair loss, and joint pain. Twenty-six percent of patients developed cutaneous squamous cell carcinoma, which was typically managed without treatment interruption.