Plexxikon advances first oncology development candidate

Preclinical data for oncogenic B-Raf inhibitor presented at American Association for Cancer Research Annual Meeting

Plexxikon Inc. today announced that the company has initiated IND-enabling studies with PLX4032, the company's oncogenic B-Raf inhibitor, a novel, small molecule drug candidate for the treatment of cancer. This compound selectively inhibits the cancer causing form of the B-Raf gene, a mutation found in 70% of skin cancers and a significant number of colorectal, ovarian and thyroid cancers. At the 97th Annual Meeting of the American Association for Cancer Research, Plexxikon scientists presented preclinical data demonstrating that a low dose of this oral V600E B-Raf inhibitor preferentially stopped tumor growth in malignant melanoma and colorectal cancer cells.

In the oral presentation titled "Development of a Novel Inhibitor of Oncogenic B-Raf," (Abstract #2412), Plexxikon scientists report that the company's V600E B-Raf inhibitor showed strong selectivity and potency against specific melanoma and colorectal cell lines. In addition, this compound demonstrated robust efficacy in xenograft models using a once-daily low oral dose, with evidence of tumor shrinkage and prolonged delay of tumor growth for a significant post-dosing period.

"Plexxikon's V600E B-Raf inhibitor may represent the first opportunity to target a disease-specific gene found only in cancerous cells and not in normal cells. With its clean selectivity profile, and specific targeting of tumors, we anticipate this drug candidate will be very safe for patients," said K. Peter Hirth, Ph.D., chief executive officer of Plexxikon Inc. "Plexxikon's advancement of this oncology candidate to development, together with our broad program in diabetes and metabolic disease, further demonstrate the depth and breadth of our novel drug discovery platform. We intend to file an IND (Investigational New Drug) application and initiate Phase 1 clinical trials in the second half of 2006 for our oncogenic B-Raf inhibitor."

Plexxikon's Oncology Programs Driven by Advent of Personalized Medicine The development of Plexxikon's novel B-Raf inhibitor will be expedited by the creation of a diagnostic test to detect a biomarker for the B-Raf mutation. Such a diagnostic test will be utilized to select patients with the B-Raf mutation for clinical trials and treatment. This mutation, known as V600E, occurs consistently in 90% of tumors harboring the oncogenic BRAF gene.

The oncogenic B-Raf inhibitor is Plexxikon's lead oncology program, with a number of other oncology opportunities with similar development profiles at the preclinical and lead optimization stage. Plexxikon's strategy in oncology focuses on targeting cancers produced by specific genetic mutations or other aberrations which correlate to poorer patient outcome and survival. By pre-selecting this sub-population of patients most likely to benefit from a selective V600E B-Raf inhibitor, Plexxikon expects to enable more rapid and effective clinical trials. The company's clinical development will be further facilitated by monitoring biomarkers that aid in dose selection and give an early read on the response of a tumor under therapy.


Plexxikon Co-Founder Schlessinger Receives Dan David Award for Cancer Innovation
In other news, the company reported today that Plexxikon co-founder Joseph Schlessinger, professor and chair of the Department of Pharmacology at Yale School of Medicine, will share the $1 million Dan David Prize for his research identifying innovative ways to treat cancer, specifically his contribution in the knowledge of tyrosine kinases. The Dan David awards, now in their fifth year, recognize persons whose achievements have made a scientific, technological, cultural or social impact on the world in three categories: past, present and future. Dr. Schlessinger was selected in the future category.

Plexxikon Profile
Plexxikon is a leader in the discovery and development of novel small molecule pharmaceuticals to treat human disease. Plexxikon's proprietary Scaffold-Based Drug Discovery platform is being applied to build therapeutic franchises in metabolic and cardiovascular disease, inflammation and oncology. This discovery process integrates a number of 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 in each of these franchises.

Currently, the company's most advanced program is a PPAR pan-agonist for the treatment of diabetes and related cardiovascular complications, with the lead candidate now in Phase 2 clinical testing in collaboration with Wyeth Pharmaceuticals. Other programs include a dual kinase inhibitor for the treatment of rheumatoid arthritis and a B-Raf inhibitor for the treatment of cancer. Plexxikon is seeking pharmaceutical and biotechnology partners for select collaboration opportunities. For more information, please visit

Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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