Josh Boger | |
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Born | Concord, North Carolina, U.S. | April 12, 1951
Education | Wesleyan University (BA) Harvard University (MA, PhD) |
Spouse | Amy Schafer |
Awards | Biotechnology Heritage Award Othmer Gold Medal |
External videos | |
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“Joshua Boger '73: Cure Entrepreneur”, Wesleyan University, Apr 6, 2011 | |
“The Innovator's Business, Managing in Balance”, Joshua Boger, February 25, 2014 |
Joshua S. Boger (born April 12, 1951) is an organic chemist and the founder of Vertex Pharmaceuticals Incorporated. He is considered a pioneer in the field of structure-based rational drug design. Drugs developed include amprenavir, an HIV protease inhibitor; telaprevir, a protease inhibitor for treatment of hepatitis C; and Kalydeco, for the treatment of cystic fibrosis. In 2003, Vertex was listed as one of forty worldwide Technology Pioneers by the World Economic Forum. As of 2012, Boger became executive chairman of Alkeus Pharmaceuticals.
Joshua S. Boger was born on April 12, 1951, in Concord, North Carolina [1] to Charles E. Boger, Jr., a textile chemist and Mary Snead Boger, an actress and writer. [2]
From 1970 to 1973, Boger attended Wesleyan University. [3] During this time Max Tishler, formerly the president of Merck Sharp and Dohme Research Laboratories, became Boger's mentor. [3] [4] Boger received a bachelor's degree in chemistry and philosophy from Wesleyan in 1973. [5]
Boger then attended Harvard University, where he worked with Jeremy R. Knowles on the chemistry of cyclodextrin. [4] He received his master's degree in 1975 and doctorate degree in chemistry in 1979. [6] He did postdoctoral research in molecular recognition with Jean-Marie Lehn from the Université Louis Pasteur in Strasbourg, France. [7]
On the recommendation of Max Tishler, Boger was hired by Merck Sharp & Dohme Research Laboratories in 1978. He initially worked on hypertension drugs, [3] developing a highly potent renin inhibitor. [8] An important step in this process was the application of computer modeling to the chemistry of drug design. [9]
Within 2 years, Boger was leading a group at Merck where he developed novel rational drug design techniques and applied them to pharmaceutical discovery and development. [10] [11] By 1987 Boger became senior director of basic chemistry at Merck Sharp & Dohme Research Laboratories, in charge of the departments of Biophysical Chemistry and Medicinal Chemistry of Immunology and Inflammation. [9]
In 1989, Boger founded Vertex Pharmaceuticals Incorporated. He has served variously as its president, CEO and chairman of the board. [12]
At Vertex, Boger pioneered an approach to structure-based rational drug design that changed the way that drug development occurred. [11] [13] The analogy often used for structure-based design is that of a lock and key: first understand the type of lock involved, and then design a key to fit that lock. Researchers sought to understand the structure of the molecules that might affect disease processes (the "lock") and then to design drugs capable of interacting with the target molecules to alter their functions (the "key"). [14] Employees worked in multi-disciplinary teams, combined technologies from biophysics, chemistry and computer science, and applied them to drug discovery [15] and the development of small molecule drugs. [16] As of 2003, Vertex was listed as one of forty worldwide Technology Pioneers by the World Economic Forum, for advancing drug discovery through this approach. [15]
While under Boger's leadership, the company worked on several potentially valuable drug treatments. Agenerase (amprenavir), an HIV protease inhibitor, was co-developed by Vertex and GlaxoSmithKline for the treatment of HIV/AIDS and approved by the FDA in 1999. [17] A second related drug was submitted for approval in 2002. [18] Lexiva (fosamprenavir) was approved by U.S. regulators on October 20, 2003. [19]
Vertex also developed Telaprevir, a protease inhibitor for treatment of hepatitis C. [20] Telaprevir works by disabling a protein that the virus requires for replication. Scientists at Vertex first published the crystal structure for the protease of the hepatitis C virus in 1996. [21] [22] As part of the development process for the drug, the company developed an elaborate systems biology model in which they modeled hepatitis C's dynamics to the level of individual patient response. [23] Telaprevir was approved by the Food and Drug Administration as Incivek in May 2011. [24]
A third product, an orally administered pill for the treatment of cystic fibrosis, grew out of the acquisition of Aurora Biosciences Corporation by Vertex in 2001. The San Diego research company had a contract with the Cystic Fibrosis Foundation, a nonprofit for patient advocacy and research, to create an assay for the disease. After the acquisition, the Cystic Fibrosis Foundation approached Vertex about expanding the contract to search for a drug treatment. The potential market for such a drug was small, unlikely to return a profit. The problem required a new approach: finding a way to turn on a non-functioning protein. Boger's decision to investigate a new area has been treated as a case study by the Harvard Business School. It is one of the first examples of venture philanthropy funding, in which a charity buys equity in a company, which then tries to solve a specific problem for them. Vertex has since developed several possible drugs for the treatment of cystic fibrosis, the first of which was Kalydeco in 2012. [25] [26]
Boger retired as CEO of Vertex as of May 23, 2009, [27] but remained on the Vertex Board of directors until June 2017. [28] The history of Vertex has been chronicled by journalist Barry Werth in The Billion-Dollar Molecule (1995) [9] [3] and The Antidote. [29]
In May 2012 Boger became executive chairman of Alkeus Pharmaceuticals. [5] Alkeus is developing a possible drug treatment for Stargardt disease, a progressive genetic condition that is a major cause of juvenile macular degeneration. [30] [4]
As of 2014, Boger was the author of over 50 scientific publications and held 32 issued U.S. patents. [9]
Boger is a founding director and chairman of NEHI (Network for Excellence in Health Innovation), [31] established in 2002. [32] He is a founding director and vice-chairman of the Alliance for Business Leadership (formerly the Progressive Business Leaders Network), established in 2006. [33] [34] [35] Boger is a member of the board of fellows of the Harvard Medical School. [6]
Boger is an advocate of liberal education who has been strongly involved with his alma mater, Wesleyan University. [36] Boger became a member of the board of trustees of Wesleyan University as of 1999, and chairman of the board of trustees as of 2009. [5] On his retirement from the board of trustees in 2016, he and his family donated $20 million to Wesleyan, over half of which established an endowed scholarship program. [36]
“In an age of instant information access, the core skills for the 21st century are information curation, critical analysis, and cross-discipline integration. Increasingly, it is apparent that needed progress in complex fields like healthcare innovation requires balance and judgment across technical, social and political areas."
Boger has been the chairman of the board of directors of the Celebrity Series of Boston. [37] Boger has also served as the vice-chairman of the Boston Museum of Science. [1]
He supports a variety of progressive and social justice causes, including the Greater Boston Food Bank. [38] [39] With Paul Sagan he has funded the Massachusetts' ACLU Technology for Liberty & Justice for All initiative. [40] He has been honored by the Jewish Alliance for Law and Social Action of Boston for his activities. [1]
In 2000, Boger combined his interests in scuba diving and photography by photographing the coral reefs off Wakaya Island near Fiji. By 2014, he was showing his underwater photography in one-man gallery shows. [41] [42] A permanent exhibit of 22 photographs, “Wakaya Octocorals and Giants,” is on display at the Exley Science Center at Wesleyan University. [36]
Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS, hepatitis C and COVID-19. These protease inhibitors prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
Vertex Pharmaceuticals Incorporated is an American biopharmaceutical company based in Boston, Massachusetts. It was one of the first biotech firms to use an explicit strategy of rational drug design rather than combinatorial chemistry. It maintains headquarters in Boston, Massachusetts, and three research facilities, in San Diego, California, and Milton Park, Oxfordshire, England.
Stuart Schreiber is an American chemist who is the Morris Loeb Research Professor at Harvard University, a co-founder of the Broad Institute, Howard Hughes Medical Institute Investigator, Emeritus, and a member of the National Academy of Sciences and National Academy of Medicine. He currently leads Arena BioWorks.
Amprenavir is a protease inhibitor used to treat HIV infection. It was approved by the Food and Drug Administration on April 15, 1999, for twice-a-day dosing instead of needing to be taken every eight hours. The convenient dosing came at a price, as the dose required is 1,200 mg, delivered in 8 (eight) very large 150 mg gel capsules or 24 (twenty-four) 50 mg gel capsules twice daily.
Venture philanthropy is a type of impact investment that takes concepts and techniques from venture capital finance and business management and applies them to achieving philanthropic goals. The term was first used in 1969 by John D. Rockefeller III to describe an imaginative and risk-taking approach to philanthropy that may be undertaken by charitable organizations.
Boceprevir is a protease inhibitor used to treat hepatitis caused by hepatitis C virus (HCV) genotype 1. It binds to the HCV nonstructural protein 3 active site.
Telaprevir (VX-950), marketed under the brand names Incivek and Incivo, is a pharmaceutical drug for the treatment of hepatitis C co-developed by Vertex Pharmaceuticals and Johnson & Johnson. It is a member of a class of antiviral drugs known as protease inhibitors. Specifically, telaprevir inhibits the hepatitis C viral enzyme NS3/4A serine protease. Telaprevir is only indicated for use against hepatitis C genotype 1 viral infections and has not been proven to be safe or effective when used for other genotypes of the virus. The standard therapy of pegylated interferon and ribavirin is less effective than telaprevir in those with genotype 1.
Many major physiological processes depend on regulation of proteolytic enzyme activity and there can be dramatic consequences when equilibrium between an enzyme and its substrates is disturbed. In this prospective, the discovery of small-molecule ligands, like protease inhibitors, that can modulate catalytic activities has an enormous therapeutic effect. Hence, inhibition of the HIV protease is one of the most important approaches for the therapeutic intervention in HIV infection and their development is regarded as major success of structure-based drug design. They are highly effective against HIV and have, since the 1990s, been a key component of anti-retroviral therapies for HIV/AIDS.
Kunitz domains are the active domains of proteins that inhibit the function of protein degrading enzymes or, more specifically, domains of Kunitz-type are protease inhibitors. They are relatively small with a length of about 50 to 60 amino acids and a molecular weight of 6 kDa. Examples of Kunitz-type protease inhibitors are aprotinin, Alzheimer's amyloid precursor protein (APP), and tissue factor pathway inhibitor (TFPI). Kunitz STI protease inhibitor, the trypsin inhibitor initially studied by Moses Kunitz, was extracted from soybeans.
Ivacaftor is a medication used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, who account for 4–5% cases of cystic fibrosis. It is also included in combination medications, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor which are used to treat people with cystic fibrosis.
Grazoprevir is a drug approved for the treatment of hepatitis C. It was developed by Merck and completed Phase III trials, used in combination with the NS5A replication complex inhibitor elbasvir under the trade name Zepatier, either with or without ribavirin.
Lumacaftor/ivacaftor, sold under the brand name Orkambi among others, is a combination of lumacaftor and ivacaftor used to treat people with cystic fibrosis who have two copies of the F508del mutation. It is unclear if it is useful in cystic fibrosis due to other causes. It is taken by mouth.
Elbasvir/grazoprevir, sold under the brand name Zepatier, is a fixed-dose combination for the treatment of hepatitis C, containing elbasvir and grazoprevir. It is used to treat chronic hepatitis C virus (HCV) genotypes 1 or 4 infection in both treatment-naïve and treatment-experienced patients.
Aurora Biosciences was a biotechnology company founded in 1995 in San Diego to commercialize fluorescence assays based on Roger Y. Tsien's discoveries concerning green fluorescent protein and its uses in basic research - work for which Tsien eventually won the 2008 Nobel Prize in chemistry along with two other chemists.
Narlaprevir, is an inhibitor of NS3/4A serine protease, intended for the treatment of chronic hepatitis C caused by genotype 1 virus in combination with other antiviral drugs.
Danoprevir (INN) is an orally available 15-membered macrocyclic peptidomimetic inhibitor of NS3/4A HCV protease. It contains acylsulfonamide, fluoroisoindole and tert-butyl carbamate moieties. Danoprevir is a clinical candidate based on its favorable potency profile against multiple HCV genotypes 1–6 and key mutants (GT1b, IC50 = 0.2–0.4 nM; replicon GT1b, EC50 = 1.6 nM). Danoprevir has been evaluated in an open-label, single arm clinical trial in combination with ritonavir for treating COVID-19 and favourably compared to lopinavir/ritonavir in a second trial.
Nancy A. Thornberry is the founding CEO and current chair, R&D at Kallyope Inc. in New York City. She previously worked with Merck Research Laboratories (MRL), joining the company in 1979 as a biochemist and retiring from the position of senior vice president and franchise head, diabetes and endocrinology in 2013.
John J. Talley is an American medicinal chemist who was the lead chemist in the discovery of the COX-2 selective nonsteroidal anti-inflammatory drug celecoxib and a co-inventor of amprenavir, a protease inhibitor used to treat HIV infection.
Jeffrey Leiden is an American physician, scientist and businessman who is the executive chairman of Vertex Pharmaceuticals, a biotechnology company based in Boston, Massachusetts. He was initially appointed to the board of directors of the company in 2009 and was CEO and president from February 2012 to March 2020.
Paul Adrian Negulescu is an American–Romanian cell biologist. He is a Senior Vice President at American pharmaceutical company Vertex Pharmaceuticals. He received the 2022 Shaw Prize in Life science and medicine, together with Michael J. Welsh, for their work that uncovered the etiology of cystic fibrosis and developed effective medications.