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Onyx Pharmaceuticals Inc. is a biopharmaceutical company headquartered in South San Francisco, California. The company develops and markets medicines for the treatment of cancer. Onyx was founded in 1992 by Kevin J. Kinsella and Frank McCormick Ph.D., FRS. In 2009, the company acquired Proteolix, Inc., a private biotechnology company. In January 2012, the company was named "the top biotechnology takeover target in 2012" through an industry survey. Onyx CEO Tony Coles has said Onyx likes it prospects as an independent company and is focused on bringing new therapies to patients. However, at the end of August 2013, Amgen announced it was acquiring Onyx in an agreed $10.4 billion deal.Other backers of Onyx were Avalon Ventures, IVP, J. H. Whitney & Company, and Kleiner Perkins Caufield & Byers. Wikipedia.

Basler M.,University of Konstanz | Kirk C.J.,Onyx Pharmaceuticals | Groettrup M.,University of Konstanz
Current Opinion in Immunology | Year: 2013

Treatment of cells with interferon-γ leads to the replacement of the constitutive catalytic proteasome subunits β1, β2, and β5 by the inducible subunits LMP2 (β1i), MECL-1 (β2i), and LMP7 (β5i), respectively, building the so-called immunoproteasome. The incorporation of these subunits is required for the production of numerous MHC class-I restricted T cell epitopes. Recently, new evidence for an involvement of the immunoproteasome in other facets of the immune response emerged. Investigations of autoimmune diseases in animal models and a genetic predisposition of β5i in human autoimmune disorders suggest a crucial function of the immunoproteasome in proinflammatory diseases. The recent elucidation of the high-resolution structure of the immunoproteasome will facilitate the design of immunoproteasome selective inhibitors for pharmacological intervention. © 2012 Elsevier Ltd. Source

Huber E.M.,TU Munich | Basler M.,University of Konstanz | Basler M.,University of Constance | Schwab R.,University of Konstanz | And 5 more authors.
Cell | Year: 2012

Constitutive proteasomes and immunoproteasomes shape the peptide repertoire presented by major histocompatibility complex class I (MHC-I) molecules by harboring different sets of catalytically active subunits. Here, we present the crystal structures of constitutive proteasomes and immunoproteasomes from mouse in the presence and absence of the epoxyketone inhibitor PR-957 (ONX 0914) at 2.9 resolution. Based on our X-ray data, we propose a unique catalytic feature for the immunoproteasome subunit β5i/LMP7. Comparison of ligand-free and ligand-bound proteasomes reveals conformational changes in the S1 pocket of β5c/X but not β5i, thereby explaining the selectivity of PR-957 for β5i. Time-resolved structures of yeast proteasome:PR-957 complexes indicate that ligand docking to the active site occurs only via the reactive head group and the P1 side chain. Together, our results support structure-guided design of inhibitory lead structures selective for immunoproteasomes that are linked to cytokine production and diseases like cancer and autoimmune disorders. © 2012 Elsevier Inc. Source

Kirk C.J.,Onyx Pharmaceuticals
Seminars in Hematology | Year: 2012

Proteasome inhibition is a validated therapeutic strategy for the treatment of B-cell neoplasms. The peptide boronate based inhibitor bortezomib has become an important tool in the armamentarium for the treatment of multiple myeloma (MM) and has spurred the development of new agents that target the catalytic activities of the proteasome. Five of these agents, representing three distinct chemical classes, have reached clinical testing. These compounds have properties similar to and distinct from bortezomib. Here, the preclinical activity and clinical development of these agents are reviewed with special attention given to comparisons with bortezomib. © 2012 Elsevier Inc. Source

News Article | March 10, 2015
Site: www.xconomy.com

In Oncology Shuffle, Amgen To Shutter Onyx, Lay Off About 300 [Updated 3/10/15 4:48 pm. See below.] Amgen subsidiary Onyx Pharmaceuticals delivered good news last week. But it has received bad news in return. Thousand Oaks, CA-based Amgen (NASDAQ: AMGN), which bought Onyx in August 2013 for $10.4 billion, is shutting down Onyx’s South San Francisco, CA, facility and plans to lay off about 300 people, Xconomy has learned. That’s about 40 percent of Onyx’s remaining staff of 750. [Editor’s note: This story’s headline has changed to read “About 300″ instead of “At Least 300.”] The news was announced Monday in a company wide memo from CEO Bob Bradway, obtained by Xconomy. Bradway wrote that the layoffs are part of a larger restructuring of Amgen’s oncology business. A company spokesman confirmed the news Tuesday. Just last week, Onyx reported that its flagship multiple myeloma treatment carfilzomib (Kyprolis) outperformed rival bortezomib (Velcade) in a head to head Phase 3 study. With the caveat that the results were not final, Amgen and Onyx said that patients taking a combination of carfilzomib and the steroid dexamethasone lived twice as long with their disease stalled—what’s known as progression-free survival—as patients taking bortezomib and dexamethasone. The full data set will be presented later this year at the American Society of Clinical Oncology conference. [This paragraph has changed to reflect a request for clarification that we received from Amgen.] Bradway’s memo stated that oncology development and commercial activities will be moved to Amgen’s Thousand Oaks headquarters on the outskirts of Los Angeles. He also wrote that “all Onyx U.S. field (sales and medical) staff will be offered roles” within Amgen. “The layoffs will affect primarily non-sales force commercial staff,” Amgen spokesman Cuyler Mayer told Xconomy. Of 750 total Onyx employees, about 300 will be laid off, 250 field staff will be offered jobs, and the status of the remaining 200 or so employees is to be determined, which means the layoff count could grow in coming months. Some Onyx staffers will move to Amgen’s South San Francisco R&D site, about a mile away from Onyx headquarters. The site will “continue to grow,” according to the memo. Bradway said Amgen will notify Onyx workers of their long-term status by late April. The layoffs will take place at the end of the year. “To build on our competitive presence in the rapidly evolving oncology field, and as part of our ongoing transformation across the company, we have decided to combine Amgen’s scale and immuno-oncology expertise with Onyx’s highly successful approach to hematologic malignancies,” Bradway wrote in the memo. “These combined oncology capabilities will create the focus and efficiency Amgen requires to progress our vision in oncology, and to remain a world leader for the long term.” Amgen has grown from a big biotech into one of the world’s biggest biopharma companies; it even began paying investors a dividend in 2011. With that growth has come turbulence. In recent months Amgen has battled a breakup effort by New York hedge fund investor Dan Loeb of Third Point, who lobbied last fall to split Amgen into two parts: one to house its mature products, the other to house its R&D efforts. Meanwhile, Amgen has announced a series of layoffs—including more than 1,000 combined last summer in the Seattle area and Colorado. The Onyx decision is the latest move to reduce and consolidate staff. Carfilzomib was approved to treat multiple myeloma in 2012. One year later, Amgen paid a hefty price for Onyx. Carfilzomib brought Amgen $331 million in 2014 revenues. It has also had ups and downs in R&D, with some late-stage success, such as the head-to-head results with bortezomib, and some failures, such as a Phase 3 trial to treat relapsed/refractory multiple myeloma that did not meet its primary endpoint. These types of layoffs are common in biopharma when a big deal goes down: jobs become expendable or up for review. Just last week, for instance, Merck reportedly revealed plans to shut down Cubist’s drug discovery efforts and eliminate 120 jobs, according to the Boston Business Journal. Merck closed its $9.5 billion buyout of Cubist in late January.

Dublin - Research and Markets (http://www.researchandmarkets.com/research/bv3584/global_multiple) has announced the addition of the "Global Multiple Myeloma Drug Market & Pipeline Insight 2015" report to their offering. 3 (Logo: http://photos.prnewswire.com/prnh/20130307/600769 ) Multiple myeloma incidences are increasing across the globe and presently available therapeutics are unable to offer effective clinical benefits. Multiple myeloma chemotherapeutics shows modest pharmacological efficacy due to which necessity for better options are required. Surgery and radiation are equally ineffective and they are not viable for most of the cases. Pharmaceutical companies have identified this scenario due to which they are investing more funds in research and development segment. As a result, investigators would be able to screen more lead molecules for their safety and efficacy in multiple myeloma. Innovative modalities are being studied in clinical trial and they are expected to yield significant results thereby surpassing the issues related with presently available modalities in coming years.  In past few decades several methods for treatment of multiple myeloma has been developed by investigators. Surgery could be performed for transplanting bone marrow from healthy donor. Radiation therapy has modest effect because myeloma cells are spread throughout the body which means higher dosage are required. Chemotherapeutics have been used successfully in past few decades for multiple myeloma treatment. New modalities are being tried by investigators to decrease its morbidity and mortality rates. They are also expected to have lesser side effects and would be able to increase average survival rates. Several innovative multiple myeloma therapeutics is available in market which offers higher safety and efficacy levels. It is expected that new innovative therapeutics would be able to offer better pharmacological benefit to patients and generate significant revenues in coming years.  Stem cell transplant has been suggested by investigators as an effective way to treat multiple myeloma. These cells have capability to differentiate according to the environment in which they have been place. External cues can also be used to transform them into desired type before implanting in the body. Some researchers have proposed the use of recombinant proteins to be implanted in the bone marrow which will prevent the proliferation of multiple myeloma. More time is required to develop and refine this technology which could potentially eliminate multiple myeloma from the body. Such technologies are still under different phases of development and they are expected to take some time before entering in global market. These modalities are expected to change the way multiple myeloma is treated but lots of progress has yet to be made by investigators.  Monoclonal antibodies (mAbs) have been successfully used for the several malignancies due to their superior therapeutic efficacy and high specificity. Targeted mAbs have the ability to bind to specific cells due to which minimized side effects are observed in cancer patients. Investigators are also trying to develop targeted mAbs for treating multiple myeloma which would be offer better therapeutic effects. New modalities like cancer vaccines are also under investigation for studying their pharmacological efficacy. Vaccines for multiple myeloma are under investigation and they are expected to overcome relapse because they activates the patient's immune system. Important part of developing such vaccines is to carefully choose the correct candidate for long-term efficacy. They are also at different stages of clinical trials and strong clinical data is required before their marketing approval in coming years.  Several new developments are expected to take place in field of multiple myeloma segments in coming years. Technological advancements along with rising funding levels is expected to increase the rate of innovations for the development of multiple myeloma drug. As a result, their pipeline is expected to become strong and more clinical trials across the globe are expected to be instigated. Positive outcomes are expected from these clinical trials due to which volume of multiple myeloma therapeutics is going to increase. Simultaneously, there sales are also expected to increase due to profit erosion of presently available therapeutics. In this way, newly introduced multiple myeloma therapeutics are expected to increase several folds in coming years. Besides this, more patients are willing to pay for such therapeutics which can increase their disease free progression.  "Global Multiple Myeloma Drug Market & Pipeline Insight" Report Highlight:  - Global Multiple Myeloma Drug Market Analysis  - Global Multiple Myeloma Drug Clinical Insight by Company, Indication & Phase  - Marketed Multiple Myeloma Drugs Clinical Insight  - Mechanism of Multiple Myeloma Drug  - Global Multiple Myeloma Drug Clinical Pipeline: 164 Drugs  - Majority Multiple Myeloma Drugs in Phase-II Trials: 40  - Marketed Multiple Myeloma Drugs: 9  1. Introduction to Multiple Myeloma  2. Mechanism of Multiple Myeloma Drug  3. Global Multiple Myeloma Drug Market Analysis  4. Global Multiple Myeloma Drug Market Dynamics  5. Global Multiple Myeloma Drug Market Future Prospects  6. Global Multiple Myeloma Drug Clinical Insight by Company, Indication & Phase  7. Marketed Multiple Myeloma Drugs Clinical Insight  8. Discontinued & Suspended Multiple Myeloma Drugs in Clinical Pipeline  9. Competitive Landscape 

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