SUGEN explained

SUGEN (Sugen) was a drug discovery company focused on development of protein kinase inhibitors. It was founded in 1991, and shut down in 2003, after pioneering protein kinases as therapeutic targets and developing the successful cancer therapy sunitinib (Sutent).

Early history and focus

Sugen was founded in 1991 in Redwood City, California, by veteran biotech investor Stephen Evans-Freke and kinase researchers Joseph Schlessinger and Axel Ullrich. The name was derived from the initials of Schlessinger and Ullrich, and the "GEN" for Genetics. Sugen developed small-molecule inhibitors of protein kinases, key enzymes in signal transduction and cellular decision-making. The main focus was on oncology, though the company had collaborations in other therapeutic areas. The concept of inhibiting kinases by small molecules that mimicked the ATP structure was generally thought to be infeasible when the company was founded (due to the high (mM) concentration of ATP in cells), and Sugen has been credited with pioneering this area,[1] leading to protein kinases being the second most active area of drug development, largely based on ATP-competitive inhibitors. Sugen also had research programs on protein phosphatases, none of which led to therapeutics.

Research and drug development

Sugen went public in October 1994 (NASDAQ: SUGN).[2] In 1997, it filed its first Investigational New Drug (IND) application, for a PDGFR inhibitor, SU101.[3] This failed clinically, but was followed by a different series of compounds that inhibited VEGFR kinases (involved in angiogenesis) as well as PDGFR and Kit. Of these, SU5416 (Semaxanib) and SU6668 went into clinical trials for colon cancer in 1999. SU5416 proceeded to Phase 3 trials, while the follow-on compound, SU11248 (Sunitinib) was later approved for human use, and a related compound SU11654 (Toceranib) was approved for canine tumors.

Sugen was funded through a number of collaborative research programs with companies including ASTA Medica (pan-Her and Raf programs), Allergan (ophthalmic angiogenesis inhibition), Zeneca (EGFR and cancer), and Amgen all of which took equity stakes in the company,[4] and Taiho (cancer).[5] Conversely, Sugen was an investor in and collaborator with Selectide for the development of peptide kinase inhibitors.[6]

Mergers

Sugen was acquired by Pharmacia & Upjohn in 1999 in a stock swap valued at $650 million.[7] In December 1999, Pharmacia & Upjohn merged with Monsanto.[8] The company was renamed Pharmacia in 2002.[9] Pharmacia was then acquired by Pfizer in April 2003.[10]

Shutdown and legacy

The Pfizer-Pharmacia merger lead to major cuts in research activities, including the shut down of Sugen over the course of 2003, with the loss of approximately 350 employees. Pfizer continued the phase 3 trials and development of SU11248, now known as Sutent (sunitinib),[11] leading to Food and Drug Administration approval in January 2006 for treatment of RCC and GIST tumors. Other programs also transferred to Pfizer, including a follow-on compound to SU11248, known as SU14813, and programs on Met and PAK kinases. Work started at Sugen also contributed to the development of the ALK inhibitor crizotinib (Xalkori), FDA-approved for NSCLC in 2011.[12] [13] Sugen also generated extensive basic research on kinase biology, including the publication of almost 300 research papers, the definition of the human kinome, and the discovery of over 140 human kinase genes. Sugen alumni have gone on to major positions[14] in other pharmaceutical and kinase-focused companies. In 2010, Sutent surpassed $1bn in annual revenues for Pfizer.[15] [16]

Notes and References

  1. Garber. Ken. 16 July 2003. Research Retreat: Pfizer Eliminates Sugen, Shrinks Cancer Infrastructure (subscription required). JNCI: Journal of the National Cancer Institute. 95. 14 . 1036–1038. 10.1093/jnci/95.14.1036 . 12865446 .
  2. Web site: 5 October 1994. SUGEN COMPLETES IPO, NETS $18M + Bioworld. subscription. 2020-11-16. BioWorld.
  3. Web site: 23 July 1997. Sugen Files IND For SU101/BCNU Trial - Pharmaceutical industry news. 2020-11-16. The Pharma Letter.
  4. Web site: Making a Rush For Sugen. dead. https://web.archive.org/web/19991104134841/http://www.businessweek.com/1998/38/b3596144.htm. 4 November 1999. Bloomberg.
  5. Web site: 8 May 1998. Sugen Signs $70 Million Deal With Taiho. The Pharma Letter.
  6. Web site: 19 January 1993. SUGEN JOINS FORCES WITH SELECTIDE + Bioworld. 2020-11-16. BioWorld.
  7. Web site: 15 June 1999. Pharmacia acquires Sugen - Jun. 15, 1999. 2020-11-16. CNN Money.
  8. Web site: 20 December 1999. Pharmacia & Upjohn agrees to merge with Monsanto, creating $50 billion. 2020-11-16. The Pharma Letter.
  9. Web site: Teitelman. Robert. 18 February 2019. Big Pharma Can't Resist Big Mergers. Here's Why.. 2020-11-16. Barrons. en-US.
  10. Web site: 16 April 2003. It's official: Pfizer buys Pharmacia - Apr. 16, 2003. 2020-11-16. CNN Money.
  11. Schlessinger. Joseph. SU11248: Genesis of a New Cancer Drug. The Scientist. 19. 17–24. https://web.archive.org/web/20050419104256/http://www.the-scientist.com/2005/4/11/17/1. 19 April 2005.
  12. Web site: Pettypiece. Shannon. 7 June 2010. Pfizer Drug Targets Gene Flaw to Shrink Lung Tumors (Update1). dead. https://web.archive.org/web/20100608020206/http://www.businessweek.com/news/2010-06-05/pfizer-drug-targets-gene-flaw-to-shrink-lung-tumors-update1-.html. 8 June 2010. Bloomberg Businessweek.
  13. 10.1021/cen-v088n030.p020 . 88 . Crizotinib Chronicles . Chemical & Engineering News . 20–21 . Jarvis . Lisa M.. 2010 . 30 .
  14. Web site: The Spirit Of A Startup Lives On. https://web.archive.org/web/20060314105044/http://www.businessweek.com/magazine/content/05_47/b3960122.htm. dead. March 14, 2006. BusinessWeek.
  15. Web site: Pfizer 2010 annual financial review, p 25..
  16. News: Berkrot. Bill. 2010-06-16. Pfizer sues Mylan over Sutent patent infringement. en. Reuters. 2020-11-16.