Profile: Onyx Pharmaceuticals Inc (ONXX.OQ)

Onyx Pharmaceuticals, Inc. (Onyx), incorporated in February 1992, is a biopharmaceutical company. The Company is developing therapies that target the molecular mechanisms that cause cancer. The Company has built two franchise platforms: one in kinase inhibition and one in proteasome inhibition. In its kinase inhibitor franchise, its product, Nexavar (sorafenib) tablets is approved for unresectable liver cancer and advanced kidney cancer. unresectable liver cancer and advanced kidney cancer. With its development and marketing partner Bayer HealthCare Pharmaceuticals Inc., or Bayer, the Company shares equally in the profits and losses of Nexavar worldwide except Japan. A kinase inhibitor, regorafenib, is an investigational agent that has already demonstrated positive Phase 3 survival data in metastatic colorectal cancer, and is being evaluated in a Phase 3 study in gastrointestinal stromal tumors (GIST).

In its proteasome inhibitor franchise, its agent is carfilzomib for the treatment of patients with multiple myeloma and solid tumors. Carfilzomib is a late-stage compound with the potential for accelerated marketing approval in the United States based on its clinical trial data and assuming a favorable regulatory outcome. The Company is also developing two other proteasome inhibitors, including an oral protease inhibitor oprozomib (ONX 0912) and an immunoproteasome inhibitor (ONX 0914). The Company has expanded its pipeline through its collaboration with Bayer HealthCare Pharmaceuticals Inc. (Bayer), including regorafenib, an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase (RTK); through its acquisition of anti-cancer compounds, including carfilzomib, a selective proteasome inhibitor the Company is developing for the potential treatment of patients with multiple myeloma and solid tumors, and through the acquisition of rights to development-stage and anti-cancer agents.

Nexavar

Nexavar, is approved by the United States Food and Drug Administration (FDA), for the treatment of patients with unresectable liver cancer and advanced kidney cancer. Nexavar is an orally available multiple kinase inhibitor that acts through dual mechanisms of action by inhibiting angiogenesis and the proliferation of cancer cells. Nexavar inhibits the signaling of VEGFR-1, VEGFR-2, VEGFR-3 and PDGFR-ß, key receptors of Vascular Endothelial Growth Factor (VEGF), and Platelet-Derived Growth Factor (PDGF). Both receptors play a role in angiogenesis. Nexavar also inhibits RAF kinase, an enzyme in the RAS signaling pathway. Nexavar also inhibits other kinases involved in cancer, such as KIT, FLT-3 and RET.

The Company’s clinical trials with Bayer include Liver Cancer Program , Kidney Cancer Program , Non-Small Cell Lung Cancer (NSCLC) Program , Thyroid Cancer Program and Breast Cancer Program. The randomized, double-blind, placebo-controlled Phase 3 study, known as Sorafenib and Erlotinib, a Randomized Trial Protocol for the Treatment of Patients with HCC (SEARCH), completed enrollment in early 2011. The Company and Bayer are actively screening patients for an international Phase 3 trial to evaluate Nexavar tablets in combination with capecitabine for the treatment of patients with locally advanced or metastatic HER2-negative breast cancer who are resistant to or have failed prior taxane and an anthracycline or for whom further anthracycline therapy is not indicated, which is known as the RESILIENCE trial. The primary endpoint of the study is progression-free survival.

Carfilzomib

The Company is developing carfilzomib, a next-generation, selective proteasome inhibitor, as a potential cancer treatment. The proteasome is a protein complex that exists in all cells, whether healthy or cancerous. Carfilzomib is a small molecule, belonging to a class known as peptide ketoepoxides, and is designed to inhibit the proteasome and enable sustained suppression of protein degradation in tumor cells. Carfilzomib is in multiple clinical trials, which include Multiple Myeloma Program.

The Company is conducting multiple clinical trials evaluating carfilzomib as a monotherapy in relapsed and/or refractory multiple myeloma patients and in combination with other anti-cancer agents and chemotherapies. In December 2011, the FDA granted Standard Review designation to the New Drug Application (NDA) for carfilzomib for the potential treatment of patients with relapsed and refractory multiple myeloma. In May 2011, data was presented from a Phase 1b/2 combination study, known as the 006 trial, of carfilzomib with lenalidomide and dexamethasone in patients with relapsed multiple myeloma. In December 2011, results of a Phase 1/2 trial were presented at the American Society of Hematology demonstrating a 100% overall response rate and minimal toxicity.

Oprozomib (ONX 0912)

Oprozomib is an oral proteasome inhibitor in Phase 1b/2 clinical development that is based on similar chemistry as carfilzomib. Oprozomib has demonstrated preclinical anti-tumor activity and a broad therapeutic window in preclinical models. During the year ended December 31, 2011, it initiated a Phase 1b/2 study of oprozomib to assess optimal dosing in patients with hematologic malignancies.

ONX 0914

The Company is developing ONX 0914 to be an inhibitor of the immunoproteasome, with minimal cross-reactivity for the constitutive proteasome. The immunoproteasome regulates the production of several inflammatory cytokines, including Tumor Necrosis Factor-alpha(TNF-alpha), Interleukin-6 (IL-6), IL-17, and IL-23. In preclinical models of rheumatoid arthritis and lupus, ONX 0914 blocked progression of these diseases at well tolerated doses. The Company is conducting preclinical studies to evaluate the potential clinical applications of ONX 0914 in the treatment of autoimmune disorders, such as rheumatoid arthritis, inflammatory bowel disease and lupus.

ONX 0801

ONX 0801 is a targeted oncology compound in Phase 1 clinical development that is designed to combine two approaches to improve outcomes for cancer patients by selectively targeting tumor cells through the alpha-folate receptor, which is overexpressed in a number of tumor types, and inhibiting thymidylate synthase (TS), a key enzyme responsible for cell growth and division. The Company obtained worldwide product development and commercialization rights to ONX 0801 through a development and license agreement with BTG International Limited (BTG). In accordance with its investment and portfolio management strategy, the Company has made the decision not to continue development of ONX 0801 and are evaluating opportunities such as partnering or licensing of the agent.

The Company competes with AVEO Pharmaceuticals, Inc., Merck & Co. and Novartis AG.