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Raymond Schinazi

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Raymond F. Schinazi (born 21 March 1950) is an Egyptian organic medicinal chemist. He is the Frances Winship Walters Professor of Pediatrics at Emory University. He has expertise in antiviral agents, pharmacology, and biotechnology. His research focuses on developing treatments for infections caused by human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV), herpes, dengue fever, zika, chikungunya, and other emerging viruses. These treatment options include antiviral agents as well as synthetic, biochemical, pharmacological and molecular genetic approaches, including molecular modeling and gene therapy.[1]

Early life and education

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Schinazi was born on March 21, 1950, in Alexandria, Egypt to Jewish parents.[2] In 1962, his family was sequestered by the Nasser regime and in 1964 they immigrated to Naples, Italy as refugees. Schinazi went to boarding school in England where he completed his early education, before being admitted as an undergraduate at the University of Bath in 1968. He received his BSc in chemistry in 1972, and remained at Bath to complete his PhD in 1976. In 2006 he was awarded an honorary doctorate in Biotechnology from the University of Bath. In 1976, he moved to Yale University's department of pharmacology and trained as a postdoctoral fellow with William Prusoff.[3][4][5]

He also completed postdoctoral trainings in virology at the University of Chicago with Bernard Roizman and at University of North Carolina with Yung-Chi Cheng, and virology/immunology at Emory University with André Nahmias.[5]

Career

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Schinazi is currently the Frances Winship Walters Professor of Pediatrics, Director of the Laboratory of Biochemical Pharmacology,[5] and co-director of the HIV Cure Scientific Working Group within the NIH-sponsored Emory University Center for AIDS Research (CFAR)[6] in Atlanta, Georgia. He has served at Emory University for 39 years since 1978.[7] He also holds Adjunct Professor positions at both University of Georgia (Atlanta, GA)[8] and University of Miami (Miami, Florida).[9] He worked part-time for the Emory University affiliated Atlanta VA for 35 years while maintaining his Emory University appointment, retiring from the VA in 2016.[10]

He began his work as a herpes virologist with a specific focus on developing drug therapeutics for orolabial and genital herpes and severe life-threatening infections like herpes encephalitis. When HIV was identified as a virus in the 1980s, Schinazi and his fellow researchers directed their attention towards the problem. He was able to translate his knowledge gained through his work on the herpes viruses towards addressing HIV and HBV. He is credited for setting up the first-ever HIV laboratory at Emory University complete with a protocol on how to handle the dangerous virus in the laboratory setting so he and his team could pursue the development of novel antiviral drugs.[5][11] In 1987, he helped Prusoff's laboratory discover that d4T, a nucleoside analog, had selective activity against HIV.[4][12]

Schinazi is best known for his involvement in the discovery and development of innovative anti-HIV, HBV, and HCV drugs on the market. To date, he has been involved in the development of five FDA-approved drugs of which three are used in eight different drug combinations.[4] More than 94% of HIV-positive people take at least one of the drugs he invented.[10][7] He has authored more than 550 peer-reviewed papers in academic literature with over 20,000 total citations.[13][14]

Discovery and development of lamivudine (3TC)

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Among the first drugs discovered and developed for treatment of HIV came through the collaboration between Dennis C. Liotta (Emory) and Schinazi. In 1992, they first published on lamivudine (3TC) in Antimicrobial Agents and Chemotherapy.[15] This drug became one of the most successful antiviral agents used to combat HIV as part of fixed-dose combinations (including Combivir, Trizivir, Epzicom, and Triumeq). Combination therapies incorporating 3TC quickly became the standard of care, with safe and effective nucleoside reverse transcriptase (RF) inhibitors, such as 3TC and its related cousins, serving as the cornerstones of combination chemotherapy.[16][17] 3TC was also found to be active against HBV in collaboration with Drs. Dennis Liotta, Philip Furman and Yung-Chi Cheng.[18][19][20]

Discovery and development of emtricitabine [(-)-FTC or FTC]

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Schinazi's work led to the discovery of a second nucleoside analog, emtricitabine (FTC), subsequently resulting in a potent, safe nucleoside analog commonly used in treatment regimens.[21] The discovery of FTC was first published in 1992 in Antimicrobial Agents and Chemotherapy as another new anti-HIV compound.[22] The mechanism of action of FTC is by incorporation of FTC-TP into the growing viral DNA strand results in chain termination, disrupting viral DNA synthesis. Disruption of this process results in rapid reduction of systemic viral loads to undetectable in HIV-infected individuals, effectively allowing for significant rebound of CD4+ T-cells, effectively providing a tandem mechanism resulting in control of systemic viremia and restoration of functional immunity.

In addition, FTC in combination with tenofovir disoproxil fumarate (Truvada) was approved as a prophylactic drug (part of PrEP) to prevent transmission of HIV, further broadening its use beyond HIV-positive people to that of prophylaxis, underscoring a novel and previously unmet need with ramifications for global health worldwide. Today, this drug is widely used as part of fixed-dose combination drug regimens, including Truvada, Atripla, Complera, Stribild, Descovy, Genvoya, Odefsey, Descovy, Biktarvy, and Symtuza.[23][20] Like 3TC, FTC was found to be active against HBV, but was never approved for this indication by the US FDA.[24][25][26][27]

Sofosbuvir (Sovaldi)

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In 2004, Schinazi was one of the founders of Pharmasset, a company that would later go on to develop sofosbuvir.[28] The name Pharmasset was derived from 'pharmaceutical assets' and the original business plan was to create assets that would be sold to other companies.[29] The company raised around $45M in its 2007 IPO at $9 per share. It would later be taken over at $137 per share. In November 2011, Gilead Sciences announced a takeover bid for Pharmasset for approximately $11.4 billion.[30]

Schinazi's contribution to the discovery of sofosbuvir is contentious. He is the co-author of a 2005 paper that discovered a precursor to the drug.[31] Jean-Pierre Sommadossi, a principal founder of Idenix and a co-founder of Pharmasset, is a former business partner who no longer speaks to Schinazi.[31][32]

In litigation between Idenix and Gilead/Pharmasset, there was an Order denying Idenix's motion for enhanced damages where the court noted that Schinazi "violated his confidentialy obligations to Idenix, and shared with Pharmasset scientists Idenix's proprietary discoveries relating to treatment of HCV".[33] However, even “fully accepting Idenix’s view of the evidence,” it was the company Schinazi founded, Pharmasset, not Idenix, that synthesized the key “compound that led to a cure for HCV.”.[34] Even accepting that Idenix discovered a component of the compound, the cure for HCV was discovered only after Pharmasset/Gilead's ”revolutionary refinement of that invention.”[35] Patent law, according to the order, reflects a balance between protection “and the importance of facilitating the imitation and refinement through imitation that are necessary to invention itself and the very lifeblood of a competitive economy.”[36]

In 2014, Schinazi, working with the Egyptian government and Gilead Sciences, agreed to provide Egypt with the drug Sofosbuvir (Sovaldi) for about US$1,000, which is only one percent of its market price. Also working with Pharco, an Egyptian Pharmaceutical company Sovaldi is now available for less than US$120 per cure. In Egypt, there is currently a total of around 12 million Egyptians infected with hepatitis C.[2]

Other drugs

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Schinazi has also had a hand in the development of the other FDA-approved drugs stavudine and telbivudine.[31]

Honors and awards

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In 2018, Schinazi received the Chevalier de la Légion d’honneur, the French Legion of Honor, with the rank of knight.[37] Established in 1802 by Napoleon Bonaparte, it is the highest decoration bestowed in France and recognizes outstanding service to the French Republic. He is the recipient of numerous other awards, including: the Bruce Witte (Blumberg) Annual Distinguished Award- Hepatitis B Foundation (2000);[38]</ref> Distinguished Scientist Award- Hepatitis B Foundation (2006);[39] Emory University's Dean's Distinguished Faculty Lecture and Award (2008);[40] Inductee- Technology Hall of Fame of Georgia (2011);[41] Intellectual Property Legends Award- Georgia State University (2012);[citation needed] Charter Fellow- National Academy of Inventors (2013);[42] Distinguished Medical Science Award- Friends of the National Library of Medicine (2013);[43]</ref> Distinguished Scientific Achievement Award- American Liver Foundation (2014);[44] Research & Hope Award for Excellence in Academic Research- PhRMA Foundation (2014);[citation needed] William S. Middleton Award- US Veterans Affairs (2015);[45] Tom Glaser Leadership Award- Connexx Eagle Star Awards (2015);[10] Lifetime Achievement Award- Scrip Award, London (2016);[46] Lifetime Achievement Award for Public Service- Institute of Human Virology (2016).[47]

He also received the Intellectual Property Legends Award and is a charter fellow of the National Academy of Inventors, was inducted into the Technology Hall of Fame of Georgia, and the Georgia Biomedical Industry Growth Award.[citation needed] In 2023, Schinazi and colleagues received the "Deal of the Year" award from Emory's Office of Technology Transfer for their licensing agreement with Phizer, Inc. (https://www.linkedin.com/comm/feed/update/urn%3Ali%3Aactivity%3A7095106988258308096?midToken=AQFWcWc1Z4SzIg&midSig=0vhYSMs6SecGU1&trk=eml-email_notification_single_mentioned_you_in_this_01-notifications-1-hero~card~feed&trkEmail=eml-email_notification_single_mentioned_you_in_this_01-notifications-1-hero~card~feed-null-les7~ll4250kv~2q-null-voyagerOffline&lipi=urn%3Ali%3Apage%3Aemail_email_notification_single_mentioned_you_in_this_01%3B88Z45snOTeSqTd3iTz%2FYsg%3D%3D)

Founder

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Schinazi has been a founder of:

  • Triangle Pharmaceuticals, which was taken over by Gilead Sciences
  • Pharmasset, also taken over by Gilead
  • Idenix Pharmaceuticals, taken over by Merck for $3.85 billion[48]
  • RFS Pharma, which merged with Cocrystal Pharma. RFS are the initials of Schinazi's name.

References

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  1. ^ "Yerkes -- Raymond Schinazi, PhD". Emory. Retrieved July 6, 2020.
  2. ^ a b "Egyptian-born hep C drug inventor meets health minister - Politics - Egypt". Ahram Online. September 26, 2014. Retrieved July 6, 2020.
  3. ^ Cookson, Clive (July 27, 2014). "Raymond Schinazi fled Nasser's Egypt to become pioneer in antivirals". Financial Times. Retrieved June 8, 2018.
  4. ^ a b c "King of the pills". Joncohen.org. May 8, 2015. Retrieved June 8, 2018.
  5. ^ a b c d "Atlanta Pediatric Research - Raymond Schinazi, PhD, DSc - Faculty - People - Emory + Children's + GT - Atlanta Pediatric Research Alliance". Pedsresearch.org. Retrieved June 8, 2018.
  6. ^ "CFAR - HIV Cure Scientific Working Group". Cfar.emory.edu. Retrieved June 8, 2018.
  7. ^ a b "Where There's A Cure There's Controversy: Raymond Schinazi's Story". Scrip.pharmamedtechbi.com. February 13, 2017. Retrieved June 8, 2018.
  8. ^ Creations, Plexus Web. "UGA Center for Drug Discovery Faculty". Uga-cdd.org. Archived from the original on January 2, 2008. Retrieved June 8, 2018.
  9. ^ "Division of Infectious Diseases at Miller School of Medicine". medicine.med.miami.edu. Retrieved June 8, 2018.
  10. ^ a b c "Emory Virologist Raymond Schinazi Honored". Atlanta Jewish Times. December 6, 2016. Retrieved June 8, 2018.
  11. ^ "American Liver Foundation awards Emory inventor with Distinguished Scientific Achievement Award". news.emory.edu. November 21, 2014. Retrieved June 8, 2018.
  12. ^ Prusoff, William (March 19, 2001). "The Scientist's Story". New York Times. Retrieved June 8, 2018.
  13. ^ "Raymond F Schinazi's Publons profile". Publons. Retrieved July 6, 2020.
  14. ^ "Scopus preview". Scopus.com. Retrieved June 8, 2018.
  15. ^ Schinazi, R F; Chu, C K; Peck, A; McMillan, A; Mathis, R; Cannon, D; Jeong, L S; Beach, J W; Choi, W B; Yeola, S (1992). "Activities of the four optical isomers of 2',3'-dideoxy-3'-thiacytidine (BCH-189) against human immunodeficiency virus type 1 in human lymphocytes". Antimicrobial Agents and Chemotherapy. 36 (3): 672–6. doi:10.1128/AAC.36.3.672. PMC 190578. PMID 1320365.
  16. ^ "At gathering of HIV/AIDS pioneers, raw memories mix with current conflicts". Sciencemag.org. October 25, 2016. Retrieved June 8, 2018.
  17. ^ Portsmouth, S. D; Scott, C. J (2007). "The renaissance of fixed dose combinations: Combivir". Therapeutics and Clinical Risk Management. 3 (4): 579–83. PMC 2374941. PMID 18472979.
  18. ^ U.S. Expired - Fee Related US7468436B2, Dennis C. Liotta; Raymond F. Schinazi & Woo-Baeg Choi, "Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers", published 2004-09-02, issued 008-12-23, assigned to Emory University 
  19. ^ U.S. Expired US7160999B2, Dennis C. Liotta; Raymond F. Schinazi & Woo-Baeg Choi, "Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers", published 2004-02-26, assigned to Emory University 
  20. ^ a b "Archived copy" (PDF). Archived from the original (PDF) on October 3, 2021. Retrieved February 14, 2018.{{cite web}}: CS1 maint: archived copy as title (link)
  21. ^ "Emory University signs $525 million agreement with Gilead, Royalty Pharma". Emory.edu. Retrieved June 8, 2018.
  22. ^ Schinazi, R F; McMillan, A; Cannon, D; Mathis, R; Lloyd, R M; Peck, A; Sommadossi, J P; St Clair, M; Wilson, J; Furman, P A (1992). "Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine". Antimicrobial Agents and Chemotherapy. 36 (11): 2423–31. doi:10.1128/AAC.36.11.2423. PMC 284347. PMID 1283296.
  23. ^ "A to Z of antiretroviral drugs - Emtricitabine (Emtriva)". Aidsmap.com. Retrieved June 8, 2018.
  24. ^ "Antiviral activity and resolution of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane". Patents.google.com. Retrieved June 8, 2018.
  25. ^ United States Expired - Fee Related US7115584B2, Raymond F. Schinazi; John W. Mellors & Dennis C. Liotta, "HIV-1 mutations selected for by β-2′,3′-didehydro-2′,3′-dideoxy-5-fluorocytidine", published October 3, 2006, issued October 3, 2006 
  26. ^ "Antiviral activity and resolution of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane". Patents.google.com. Retrieved June 8, 2018.
  27. ^ "Treatment of HIV by administration of β-D-2′, 3′-didehydro-2′,3′-dideoxy-5-fluorocytidine (D4FC)". Patents.google.com. Retrieved June 8, 2018.
  28. ^ Sachs, Jeffrey (April 18, 2015). "The Drug That Is Bankrupting America". HuffPost. Retrieved July 6, 2020.
  29. ^ Berkrot, Bill (November 22, 2011). "Gilead could have had Pharmasset cheap: founder". Reuters. Retrieved July 6, 2020.
  30. ^ "Gilead Sciences to Acquire Pharmasset, Inc. for $11 Billion". investors.gilead.com. Archived from the original on November 15, 2017. Retrieved June 8, 2018.
  31. ^ a b c Cohen, J (2015). "King of the pills". Science. 348 (6235): 622–5. Bibcode:2015Sci...348..622C. doi:10.1126/science.348.6235.622. PMID 25953989.
  32. ^ "Gilead's Patent Loss to Merck Started With a Broken Friendship". Biglawbusiness.com. Retrieved June 8, 2018.
  33. ^ C.A. No. 14-846-LPS 2017, p. 7.
  34. ^ C.A. No. 14-846-LPS 2017, p. 15.
  35. ^ C.A. No. 14-846-LPS 2017, pp. 15–16.
  36. ^ C.A. No. 14-846-LPS 2017, pp. 7, 16.
  37. ^ Korschun, Holly (December 4, 2018). "Emory HIV/AIDS drug inventor, entrepreneur decorated with French Legion of Honor". Emory. Retrieved July 6, 2020.
  38. ^ "Bio/Med Investor Network". Archived from the original on January 9, 2019. Retrieved January 9, 2019.
  39. ^ Farley, Peggy (March 22, 2006). "Hepatitis B Foundation Presents Distinguished Scientist Award 2006 to Emory University Professor Dr. Raymond F. Schinazi, a Pioneer in Antiviral Drug Discovery Research for HIV and Hepatitis B". ReleaseWire (Press release). Doylestown, PA. SBWIRE. Retrieved July 6, 2020.
  40. ^ Lawley, Thomas J. MD (April 2008). "Emory School of Medicine - Dean's Letter". Emory. Retrieved July 6, 2020.
  41. ^ "US Newsroom". Pwc.com.
  42. ^ "Wagner, Schinazi named National Academy of Inventors Charter Fellows | Emory University | Atlanta GA". News.emory.edu.
  43. ^ "Friends of the National Library of Medicine". Archived from the original on June 20, 2018. Retrieved January 9, 2019.
  44. ^ "American Liver Foundation awards Emory inventor with Distinguished Scientific Achievement Award | Emory University | Atlanta GA". News.emory.edu.
  45. ^ "Raymond Schinazi, drug-development pioneer, earns VA's highest honor for biomedical research". Research.va.gov.
  46. ^ Scrip Team (November 30, 2016). "Industry's Achievements Lauded At 12th Annual Scrip Awards". Scrip Pharma Intelligence. Retrieved July 6, 2020.
  47. ^ Korschun, Holly (September 22, 2016). "Institute of Human Virology honors Schinazi with Lifetime Achievement Awards". Emory. Retrieved July 6, 2020.
  48. ^ "Merck to Acquire Idenix". Mrknewsroom.com (Press release). June 9, 2014. Retrieved July 6, 2020.

Works cited

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  • Idenix Pharms. LLC v. Gilead Scis., Inc., 14-846-LPS (UNITED STATES DISTRICT COURT FOR THE DISTRICT OF DELAWARE September 22, 2017).
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