ONYX REJECTS AMGEN OFFER BIOTECHNOLOGY: Cancer drug firm
will likely attract other bidders
O
NYX PHARMACEUTICALS has spurned a
$10 billion takeover bid from Amgen, saying that it will instead solicit offers from other suitors. With so many big drug companies desperate to bolster their cancer portfolios, the South San Francisco-based biotech firm is expected to fetch as much as $12.5 billion. Onyx is one of just a few biotech companies to boast a wholly owned product, and it is part of an even more elite group with a cancer drug. Kyprolis (carfilzomib), a proteasome inhibitor for the treatment of a blood cancer called multiple myeloma, was approved in July 2012. Deutsche Bank stock analyst Robyn Karnauskas expects annual sales of the drug, which costs nearly $10,000 a month, will top $2.2 billion by 2019. Moreover, Onyx has a stake in several other cancer drugs. The firm’s revenues were $362 million in 2012, but they are expected to cross the $1 billion mark by 2015,
SOLVING AN OLD BONDING DEBATE CRYSTALLOGRAPHY: 2-Norbornyl
cation structure shows nonclassical bonding at last
C
HEMISTS HAVE USED a deep-freeze crystal-
lization method to solve the structure for the 2-norbornyl cation, likely closing an acrimonious 50-year debate on the nature of a fundamental bonding concept. Instead of two electrons shared between two carbon atoms, as in conventional single-bond structures, this cation structure shows nonclassical bonding, with two electrons delocalized over three carbon atoms (Science 2013, DOI: 10.1126/science.1238849). The structural analysis of the cation, a bridged cyclic hydrocarbon, was led by Ingo Krossing of the University of Freiburg and Karsten Meyer of the University of Erlangen-Nuremberg, both in Germany. The debate centered on different interpretations of thermodynamic and spectroscopic data for the cation. Last year, University of Richmond chemist and historian Jeffrey I. Seeman characterized the interactions
enough to provide even a large pharmaceutical firm with a nice boost. Although Amgen’s $120.00-per-share offer was well over Onyx’ closing stock price of $86.82 on June 28, the final trading day before the news was revealed, Onyx’ board swiftly dismissed the bid as too low. “We assume it will take significantly more than $120 to secure a deal,” JPMorgan analyst Cory Kasimov said in a note to investors. With few cancer-oriented biotech firms in the same category as Onyx and with most major drug firms O hunting for deals that can immediN N N N ately bolster their portfolios, anaH H H lysts expect that Onyx will attract a O O O lot of interest. Bayer and Pfizer top the list of likely bidders. Bayer and Onyx have a long-standing relationship that has yielded two drugs: the kidney and liver canCarfilzomib cer drug Nexavar, approved in 2005, and the colon cancer treatment Stivarga, approved last September. Nexavar sales are split evenly between the partners, and Onyx gets a 20% royalty on Stivarga revenues. As part of a decades-old pact with Pfizer, Onyx also holds an 8% royalty on future sales of palbociclib, a small molecule that shows promise in treating breast cancer. Analysts think Pfizer will get FDA’s nod to sell the drug in 2016.—LISA JARVIS
between the two sides as “crude and rude” (C&EN, Nov. 19, 2012, page 44). A crystal structure of the cation likely would have resolved the arguments, but that experimental evidence was elusive. Many other researchers have obtained 2-norbornyl cation crystals, but their molecular disorder stumped scientists, Krossing says. Meyer, Krossing, and colleagues managed to obtain the structure by stabilizing the 2-norbornyl cation with a bromoaluminate counterion, crystallizing the product for several days at a chilly 245 K. They developed an annealing process of cooling the crystals even H further to 40 K, then repeatedly warming and cooling the crystals to freeze out molecular disorder, allowing them to collect good X-ray data. The structure reveals the two-electron, threecarbon system as having two C–C bonds of 1.80 Å, longer than a standard 1.54-Å C–C single H bond. The third bond in the system is 1.39 Å long, similar to the delocalized C–C bonds of benzene. The work is “a triumph of creative crystallography in taming an uncooperative cation,” says theoretical organic chemist Dean J. Tantillo of the University of California, Davis. Although the existing evidence had largely convinced chemists that the nonclassical structure existed in the gas phase and in solution, the new structure demonstrates that it exists in the solid state as well, Tantillo says.—JYLLIAN KEMSLEY
CEN.ACS.ORG
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X-ray crystallography shows that the 2-norbornyl cation has a nonclassical two-electron, threecenter structure, rather than classical single bonds.
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