Saturday, December 31, 2011

OncoBrands We Used to Know in 2011

Oncology is one island where biotech investment continues in the sea of shrinking biopharma.  As expected, the current environment is also conducive to oncology biotech companies being lost to mergers and acquisitions.  Sadly, these carefully crafted and nurtured brands will be lost for ever!

Lost souls
  • Astex Therapeutics, Cambridge, UK, merged with SuperGen in April, 2011. The new company is now called Astex Pharmaceuticals, Dublin, Calif.
  • Calistoga Pharmaceuticals of Seattle was acquired by Gilead Sciences in Feb 2011 along with their gems PI3K inhibitors.
  • Calypso Medical Technology was acquired by Varian Medical Systems in Sept. 2011.
  • Sanofi SA (SNY) bought Genzyme Corp for over $20 billion.
  • Daiichi Sankyo Co. Ltd took home Plexxikon, Berkeley, Calif., for $935 million and its recently approved melanoma drug Zelboraf™ (vemurafenib).  At present Plexxikon, now a member of Daiichi, retains its identity.
  • Intellikine, Inc. was acquired by Takeda Pharmaceutical Co. Ltd. (TKDG.DE) for $310 Million in December 2011. Intellikine's portfolio: INK128, a novel mTORC1/2 inhibitor; INK1117, a novel and selective inhibitor of the PI3Ka isoform
  • There was a talk in town that Onyx Pharmaceuticals Inc. (ONXX) may sell itself or its blood cancer drug carfilzomib.
 - Gotye

Plexxikon targets BRAF(V600E) in melanoma while Intellikine develops an answer for tumor escape from vemurafenib

Plexxikon/Roche's vemurafenib (previously called PLX4950) inhibits BRAF protein that contains an activation mutation V660E which is present in nearly 50% of all melanomas.  Inhibiting BRAF(V600E) signal blocks MAPK pathway (RAS/MEK/ERK) mediated tumor cell proliferation.  This causes the tumor cells to die (under apoptosis.)  However, tumor cells learn to bypass this inhibition and resistance to vemurafenib has already started to appear in the clinic.  

Unfortunately, cells resistant to one BRAF inhibitor were also found to be resistant to most other experimental drugs which work via BRAF switch (Jessie Villanuev, et al. Cancer Cell 2010).  Resistance to vemurafenib occurs through rewiring and signaling through alternate pathways and not via additional BRAF mutations.  Tumor cells may bypass BRAF through other RAF forms (e.g., ARAF or CRAF) and continue to rely on MAPK signaling.  However, a key alternate pathway in these melanoma cells is PI3K/AKT pathway which is activated by IGF-1 growth factor  (Jessie Villanuev, et al. Cancer Cell 2010).  IGF-1 growth factor is secreted by fibroblasts in skin and it activates IGF1 receptor present on melanoma cells.

(Keith T. Flaherty. Ann Intern Med. 2010, PubMedFulltext)

Since melanoma cells proliferate through
BRAF/MAPK as well as PI3K/AKT pathways, combining drugs targeting both BRAF/MAPK and  PI3K/AKT pathway is expected minimize tumor escape and relapse.  This strategy is headed for clinic.  And, this is where Intellikine's anti-PI3K compounds may have an impact.

Ground continues to shift
"Current takeover candidates -- all of which operate at a loss -- include Dendreon (DNDN.O), Pharmacyclics (PCYC.O), Synta Pharmaceuticals (SNTA.O), Threshold Pharmaceuticals (THLD.O), Seattle Genetics (SGEN.O) and Exelixis (EXEL.O), analysts and industry bankers said." -- By Deena Beasley, Jul 13, 2011, Reuters | link |

Further readings on Lost Brands:
  • Biospace News - Mergers and Acquisitions [link
  • Seattle Biotech Graveyard. By Lyman BioPharma Consulting | link |
  • The Year in Seattle Biotech: Lots of Acquisitions, Few New Startups. Xconomy. Luke Timmerman.  Dec. 22, 2011 | link |
  • The Good, the Bad and . . . the Huh? A 2011 Biotech Recap. By Jennifer Boggs.  BioWorldBlogs.  Dec. 28, 2011 | link 
  • Advice for Future Pharma Scientists: Start Small. By Michael Price, Elisabeth Pain. Science Careers Dec. 09, 2011 [link
  • Are Pharma Layoffs Over? BioJobBlogger. Posted on October 6, 2011 [link]
  • Challenger Gray Christmas Blog @Work
  • The 2010 Biotech Graveyard. By Maureen Martino.  Oct. 5, 2010 | link |
Happy New Year 2012

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