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[4] 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,[5] and Taiho (cancer).[6] Conversely, Sugen was an investor in and collaborator with Selectide for the development of peptide kinase inhibitors.[7]

Mergers

Sugen was acquired by Pharmacia & Upjohn in 1999 in a stock swap valued at $650 million.[8] In December 1999, Pharmacia & Upjohn merged with Monsanto.[9] The company was renamed Pharmacia in 2002.[10] Pharmacia was then acquired by Pfizer in April 2003.[11]

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.[1] Pfizer continued the phase 3 trials and development of SU11248, now known as Sutent (sunitinib),[4] 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,[1] 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]

References

  1. 1 2 3 Garber, Ken (16 July 2003). "Research Retreat: Pfizer Eliminates Sugen, Shrinks Cancer Infrastructure (subscription required)". JNCI: Journal of the National Cancer Institute. 95: 1036–1038.
  2. ↑ "SUGEN COMPLETES IPO, NETS $18M + | Bioworld". BioWorld. 5 October 1994. Retrieved 2020-11-16.
  3. ↑ "Sugen Files IND For SU101/BCNU Trial - Pharmaceutical industry news". The Pharma Letter. 23 July 1997. Retrieved 2020-11-16.
  4. 1 2 Schlessinger, Joseph. "SU11248: Genesis of a New Cancer Drug". The Scientist. 19: 17–24. Archived from the original on 19 April 2005.
  5. ↑ "Making a Rush For Sugen". Bloomberg. Archived from the original on 4 November 1999.
  6. ↑ "Sugen Signs $70 Million Deal With Taiho". The Pharma Letter. 8 May 1998.
  7. ↑ "SUGEN JOINS FORCES WITH SELECTIDE + | Bioworld". BioWorld. 19 January 1993. Retrieved 2020-11-16.
  8. ↑ "Pharmacia acquires Sugen - Jun. 15, 1999". CNN Money. 15 June 1999. Retrieved 2020-11-16.
  9. ↑ "Pharmacia & Upjohn agrees to merge with Monsanto, creating $50 billion". The Pharma Letter. 20 December 1999. Retrieved 2020-11-16.
  10. ↑ Teitelman, Robert (18 February 2019). "Big Pharma Can't Resist Big Mergers. Here's Why". Barrons. Retrieved 2020-11-16.
  11. ↑ "It's official: Pfizer buys Pharmacia - Apr. 16, 2003". CNN Money. 16 April 2003. Retrieved 2020-11-16.
  12. ↑ Pettypiece, Shannon (7 June 2010). "Pfizer Drug Targets Gene Flaw to Shrink Lung Tumors (Update1)". Bloomberg Businessweek. Archived from the original on 8 June 2010.
  13. ↑ Jarvis, Lisa M. "CRIZOTINIB CHRONICLES". Chemical & Engineering News. 88: 20–21. doi:10.1021/cen-v088n030.p020.
  14. ↑ "The Spirit Of A Startup Lives On". BusinessWeek. Archived from the original on March 14, 2006.
  15. ↑ "Pfizer 2010 annual financial review, p 25" (PDF).
  16. ↑ Berkrot, Bill (2010-06-16). "Pfizer sues Mylan over Sutent patent infringement". Reuters. Retrieved 2020-11-16.
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