Regeneron Pharmaceuticals, Inc.
https://en.wikipedia.org/wiki/Regeneron_Pharmaceuticals
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Regeneron Pharmaceuticals
From Wikipedia, the free encyclopedia
Headquarters under construction, 2014
Type
Nasdaq-100 component
S&P 500 component
Industry
Founded
1988; 34 years ago
Founders
Headquarters
Tarrytown, New York, U.S.
Area served
Global
Key people
Revenue
US$16.07 billion (2021)
US$8.95 billion (2021)
US$8.08 billion (2021)
US$25.43 billion (2021)
US$18.77 billion (2021)
Number of employees
10,368 (December 2021)
Website
Footnotes / references
Regeneron Pharmaceuticals, Inc. is an American biotechnology company headquartered in Westchester County, New York. The company was founded in 1988.[2] Originally focused on neurotrophic factors and their regenerative capabilities, giving rise to its name, the company then branched out into the study of both cytokine and tyrosine kinase receptors.
Contents
The company was founded by CEO Leonard Schleifer and scientist George Yancopoulos in 1988.[3]
Regeneron has developed aflibercept, a VEGF inhibitor, and rilonacept, an interleukin-1 blocker. VEGF is a protein that normally stimulates the growth of blood vessels, and interleukin-1 is a protein that is normally involved in inflammation.[citation needed]
On March 26, 2012, Bloomberg announced that Sanofi and Regeneron were in development of a new drug that would help reduce cholesterol up to 72% more than its competitors. The new drug would target the PCSK9gene.[4]
In July 2015, the company announced a new global collaboration with Sanofi to discover, develop, and commercialize new immuno-oncology drugs, which could generate more than $2 billion for Regeneron,[5] with $640 million upfront, $750 million for proof-of-concept data, and $650 million from the development of REGN2810.[6] REGN2810 was later named cemiplimab. In 2019, Regeneron Pharmaceuticals was announced the 7th best stock of the 2010s, with a total return of 1,457%.[7] Regeneron Pharmaceuticals was home to the two highest-paid pharmaceutical executives as of 2020.[8]
In October 2017, Regeneron made a deal with the US-government Biomedical Advanced Research and Development Authority that the government would fund 80% of the costs for Regeneron to develop and manufacture antibody treatments, including now their Coronavirus disease 2019 treatments, and Regeneron would retain the right to set prices and control production.[9] This deal was criticized in The New York Times.[8]Such deals are not unusual for routine drug development in the American pharmaceutical market.
In May 2020, Regeneron announced it would repurchase around $5 billion of its shares, held directly by Sanofi. Prior to the transaction, Sanofi held 23.2 million Regeneron shares.[10]
In April 2022, the business announced it would acquire Checkmate Pharmaceuticals for around $250 million, enhancing its number of immuno-oncology drugs.[11]
Main article: Casirivimab/imdevimab
On February 4, 2020, the U.S. Department of Health and Human Services, which already worked with Regeneron, announced that Regeneron would pursue monoclonal antibodies to fight COVID-19.[12]
In July 2020, under Operation Warp Speed, Regeneron was awarded a $450 million government contract to manufacture and supply its experimental treatment REGN-COV2, an artificial "antibody cocktail" which was then undergoing clinical trials for its potential both to treat people with COVID-19 and to prevent SARS-CoV-2 coronavirus infection.[13][14][15] The $450 million came from the Biomedical Advanced Research and Development Authority (BARDA), the DoD Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, and Army Contracting Command. Regeneron expected to produce 70,000â300,000 treatment doses or 420,000â1,300,000 prevention doses. "By funding this manufacturing effort, the federal government will own the doses expected to result from the demonstration project," the government said in its July 7 news release.[16] Regeneron similarly said in its own news release that same day that "the government has committed to making doses from these lots available to the American people at no cost and would be responsible for their distribution," noting that this depended on the government granting emergency use authorization or product approval.[17] California based laboratory, FOMAT, is part of the clinical investigation through their doctors Augusto and Nicholas Focil.[18]
In October 2020 when U.S. President Donald Trump was infected with COVID-19 and taken to Walter Reed National Military Medical Center in Bethesda, Maryland, he was administered REGN-COV2.[19] His doctors obtained it from Regeneron via a compassionate use request (as clinical trials had not yet been completed and the drug had not yet been approved by the US Food and Drug Administration (FDA)).[20] On October 7, Trump posted a five-minute video to Twitter reasserting that this drug should be "free."[21] That same day, Regeneron filed with the FDA for emergency use authorization. In the filing, it specified that it currently had 50,000 doses and that it expected to reach a total of 300,000 doses "within the next few months."[22] The FDA granted approval for emergency use authorization in November 2020.[23]
Arcalyst (rilonacept) is used for specific, rare autoinflammatory conditions. Approved by the FDA in February 2008.[citation needed]
Eylea (aflibercept injection) was approved by the U.S. Food and Drug Administration (FDA) in November 2011[2][24] to treat a common cause of blindness in the elderly. Eylea is reported to cost $11,000 per year for each eye treated.[3]
Zaltrap (aflibercept injection) is used for metastatic colorectal cancer approved by the FDA in August 2012.[25]
Praluent (alirocumab) is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein (LDL) cholesterol. Approved by the FDA in July 2015,[26] It is reported to cost $4,500 to $8,000 per year.[27]
Dupixent (dupilumab injection) is for the treatment of adolescent and adult patients' atopic dermatitis. It was approved by the FDA in March 2017[28] and is reported to cost $37,000 per year.[3]
Kevzara (sarilumab injection) is an interleukin-6 (IL-6) receptor antagonist for treatment of adults with rheumatoid arthritis approved by the FDA in May 2017.[29] Trials commenced in March 2020 to evaluate the effectiveness of Kevzara in the treatment of COVID-19.[30][31]
Libtayo (cemiplimab injection) is a monoclonal antibody targeting the PD-1 pathway as a checkpoint inhibitor, for the treatment of people with metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC who are not candidates for curative surgery or curative radiation. Libtayo was approved by the FDA in September 2018.[32]
Inmazeb (atoltivimab/maftivimab/odesivimab) is a drug made of three antibodies, developed to treat deadly Ebola virus. In October 2020, the U.S. Food and Drug Administration (FDA) approved it with an indication for the treatment of infection caused by Zaire ebolavirus.[33]
Trap Fusion Proteins: Regeneron's novel and patented Trap technology creates high-affinity product candidates for many types of signaling molecules, including growth factors and cytokines. The Trap technology involves fusing two distinct fully human receptor components and a fully human immunoglobulin-G constant region.[citation needed]
Fully Human Monoclonal Antibodies: Regeneron has developed a suite (VelociSuite) of patented technologies, including VelocImmune and VelociMab, that allow Regeneron scientists to determine the best targets for therapeutic intervention and rapidly generate high-quality, fully human antibodies drug candidates addressing these targets.[34]:â255â258â
Financial Year
Revenue[35]
2012
$1.4 billion
2013
$2.1 billion
2014
$2.8 billion
2015
$4.1 billion
2016
$4.8 billion
2017
$5.8 billion
2018
$6.7 billion
2019
$7.8 billion
2020
$8.5 billion
2021
$16.1 billion
The founders Leonard Schleifer and George Yancopoulos are reported to hold $1.3 billion and $900 million in company stock, respectively. Both are from Queens, New York.[3] Schleifer was formerly a professor of medicine at Weill Cornell Medical School. Yancopoulos was an assistant professor at Columbia University. Yancopoulos was involved in each drug's development.[3]
^ "Regeneron Pharmaceuticals, Inc. 2021 Annual Report (Form 10-K)". U.S. Securities and Exchange Commission. February 7, 2022.
^
a b Herper, Matthew (August 14, 2013). "How Two Guys From Queens Are Changing Drug Discovery". Forbes. Archived from the original on March 16, 2014. Retrieved March 22, 2014.
^
a b c d e "Regeneron's Billionaire Founder Battles The Drug Pricing System". Forbes. 26 July 2018. Retrieved 26 July2018.
^ "Sanofi-Regeneron Drug Lowers Cholesterol Up to 72% in Study". Bloomberg. 26 March 2012. Retrieved 25 July 2021.
^ Staff (July 28, 2015). "Regeneron, Sanofi Launch $2B+ Immuno-Oncology Collaboration". Genetic Engineering & Biotechnology News. Archived from the original on September 21, 2020. Retrieved October 9, 2022.
^ Carroll, John (July 28, 2015). "UPDATED: Struggling Sanofi paying $1.8B to partner with Regeneron on immuno-oncology". FierceBiotech. Archived from the original on May 4, 2016. Retrieved October 9, 2022.
^ Hough, Jack (December 18, 2019). "10 Stocks That Had Better Decades Than Amazon and Google". Barron's. Archived from the original on December 18, 2019. Retrieved December 19, 2019.
^
a b Mazzucato, Mariana; Momenghalibaf, Azzi (March 18, 2020). "Drug Companies Will Make a Killing From Coronavirus". The New York Times. Archived from the original on March 18, 2020. Retrieved October 9, 2022.
^ Pagliarulo, Ned (February 4, 2020). "Regeneron partners with US government to develop coronavirus treatment". BioPharma Dive. Washington, D.C.: Industry Dive. Archivedfrom the original on February 27, 2020. Retrieved July 25,2021.
^ Protard, Matthieu (May 25, 2020). "U.S.' Regeneron to buy back $5 billion stake held by Sanofi". Reuters. Ed. John Stonestreet. Archived from the original on October 18, 2020. Retrieved October 9, 2022.
^ "Regeneron to Acquire Checkmate Pharmaceuticals and Its Investigational Immune Activator for Potential Use in Multiple Tumor Types" (Press release). Regeneron. April 19, 2022. Retrieved October 9, 2022 â via BioSpace.
^ News Division (4 February 2020). "HHS, Regeneron Collaborate to Develop 2019-nCoV Treatment". HHS.gov. Retrieved 8 October 2020.
^ Kelland, Kate (2020-09-14). "Regeneron's antibody drug added to UK Recovery trial of COVID treatments". Reuters. Retrieved 2020-10-08.
^ Morelle, Rebecca (2020-09-14). "Antibody treatment to be given to Covid patients". BBC News. Retrieved 2020-10-08.
^ "Regeneron's COVID-19 Response Efforts". Regeneron Pharmaceuticals Inc. Retrieved 2020-10-08.
^ News Division (6 July 2020). "HHS, DOD Collaborate with Regeneron on Large-Scale Manufacturing Demonstration Project of COVID-19 Investigational Therapeutic Treatment". HHS.gov. Retrieved 8 October 2020.
^ Regeneron (7 July 2020). "Regeneron Announces Manufacturing and Supply Agreement for BARDA and U.S. Department of Defense for REGN-COV2 Anti-Viral Antibody Cocktail". Regeneron Pharmaceuticals Inc. Retrieved 2020-10-08.
^ Largacha, MarĂa Cecilia (6 August 2020). "2 ecuatorianos, cerca del medicamento contra el Covid-19". YouTube. Archived from the original on 2021-12-21. Retrieved 13 October 2020.
^ "Trump taking Regeneron drug, Remdesivir therapy for coronavirus diagnosis: ex-WH doctor explains". Associated Press. Associated Press. 2020-10-03. Retrieved 2020-10-13.
^ Cunningham, Paige Winfield. "Analysis | The Health 202: Trump is taking Regeneron's new coronavirus treatment. It's used for mild symptoms" â via www.washingtonpost.com.
^ Trump, Donald (7 October 2020). "A Message From The President!". Twitter. Retrieved 7 October 2020.
^ Regeneron (7 October 2020). "Statement on REGN-COV2 Emergency Use Authorization Request (PDF)". Regeneron Pharmaceuticals Inc. Retrieved 8 October 2020.
^ Conover, Damien (January 19, 2021). "Biopharma Companies With COVID-19 Treatments See $10 Billion Market in 2021". Morningstar.com. Retrieved 2021-01-19.
^ "Regulators Approve a Drug for an Eye Condition". The New York Times. Associated Press. November 18, 2011.
^ "FDA approves Zaltrap for metastatic colorectal cancer"(Press release). U.S. Food and Drug Administration (FDA). August 3, 2012. Archived from the original on June 25, 2013.
^ "FDA approves Praluent to treat certain patients with high cholesterol" (Press release). U.S. Food and Drug Administration (FDA). Archived from the original on 2015-07-27. Retrieved 2015-07-29.
^ Tirrell, Meg (2018-05-01). "A $14,000 cholesterol drug gets a price cut as Regeneron, Sanofi strike deal with Express Scripts". CNBC. Retrieved 2018-08-22.
^ "Regeneron and Sanofi Announce FDA Approval of Dupixent (dupilumab), the First Targeted Biologic Therapy for Adults with Moderate-to-Severe Atopic Dermatitis" (Press release). Regeneron Pharmaceuticals Inc. â via PRNewswire.
^ "Regeneron and Sanofi Announce FDA Approval of Kevzara (sarilumab) for the Treatment of Moderately to Severely Active Rheumatoid Arthritis in Adult Patients (NASDAQ:REGN)". Regeneron Pharmaceuticals Inc. (Press release).
^ "Regeneron's COVID-19 Response Efforts". Regeneron Pharmaceuticals Inc.
^ "Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19". clinicaltrials.gov. 30 September 2020.
^ "FDA approves first treatment for advanced form of the second most common skin cancer". U.S. Food and Drug Administration (FDA) (Press release). 2019-09-11.
^ "FDA Approves First Treatment for Ebola Virus". U.S. Food and Drug Administration (FDA) (Press release). 14 October 2020. Retrieved 14 October 2020. This article incorporates text from this source, which is in the public domain.
^ Susana MagadĂĄn MompĂł and Ăfrica GonzĂĄlez-FernĂĄndez. "Human Monoclonal Antibodies from Transgenic Mice". Chapter 13 in Human Monoclonal Antibodies: Methods and Protocols Ed. Michael Steinitz. Springer Science+Business Media, 2014. ISBN 978-1627035859
^ "Regeneron Pharmaceuticals Revenue 2006â2021 | REGN". www.macrotrends.net. Retrieved 2021-07-26.
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2020-04-20-bloomberg-com-antibody-treatments-may-be-the-best-hope-against-the-virus-until-a-vaccine.pdf
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Antibody Treatments May Be the Best Hope Against the Virus Until a Vaccine
Regeneronâs drug cocktail could be tested in humans by summer and be saving lives by fall.
ByRobert Langreth and Susan Berfield
April 20, 2020, 5:00 AM EDT
Share this article
The novel coronavirus is devious, persistent, and, according to some scientists, not even alive. But, as the world has had to learn, this tiny bundle of genetic material is a highly efficient invader. Each particle is armored with roughly 100 protrusions, or spikes, perfectly evolved to latch onto an enzyme on the surfaces of throat and lung cells, then slip into them and replicate millions and millions of times.
Older coronaviruses, such as the one that caused severe acute respiratory syndrome, or SARS, operated similarly. The spikes of the new coronavirus, though, clasp human cells much more tightly, which appears to be one reason it spreads more easily. In the three months since scientists in China identified it, the coronavirus has infected more than 2.4 million people around the world and killed at least 165,000.
Neutralizing those spikes may be the best way to prevent the virus from harming its host. And among the most promising approaches to doing that is finding the right antibodies. Multiple companies are doing this, using antibodies from laboratory mice and recovered patients. Unlike existing medicines being tested on the virusâsuch as hydroxychloroquine, the malaria drug controversially touted by President Trump, and remdesivir, an antiviral compound originally developed by Gilead Sciences Inc.to fight Ebolaâantibody drugs are being designed specifically to disable the new virus where itâs most vulnerable.
Theyâre taking advantage of sophisticated technologies developed over the past two decades to create exquisitely targeted medicines. If they work, the therapies could be used in two crucial ways: to treat those already infected and, in the absence of a vaccine, as a short-term prophylactic for those at high risk.
Normally it can take five or more years to develop a drug and move it into human trials. No one wants to wait that long. AstraZeneca, Vir Biotechnology, and Eli Lilly and its biotech partner, AbCellera Biologics, as well as several academic labs, are hoping to start human trials by the end of summer. If all goes well, antibody treatments for those most in need could be available by fall.
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U.S. Government Money Invested in Coronavirus Countermeasures
As most recently reported by the Biomedical Advanced Research and Development Authority. May not include all funding awarded. *Funding for vaccines may be up to $970 million, including options.
Data: U.S. Department of Health and Human Services, SAb Biotherapeutics
Regeneron Pharmaceuticals Inc. expects to move at least as fast. The company is known in the industry for its VelocImmune mice, genetically engineered to develop humanlike antibodies when injected with viral DNA. In this case, Regeneron used genetic material identical to that of the virus in several dozen mice, provoking an immune response. About a month later the scientists removed the miceâs spleens and extracted thousands of antibodies that had developed in response to the viral material. They began sorting through the antibodies, and in mid-April selected a few of the most potent ones to produce at one of Regeneronâs main manufacturing sites for animal trials. News of that milestone produced another bump for the companyâs stock, which at press time was the best performer of 2020 on the S&P 500 index. Human trials could begin in June.
Itâs possible that none of the antibody treatments Regeneron or any of the other companies develop will be effective. Or they may produce unexpected side effects that limit their use. But many who are watching the research closely think at least one of these treatments will be successful. âThe odds are very high this will work, especially when you have multiple programs and multiple manufacturers,â says James Crowe, a veteran immunologist at Vanderbilt University Medical Center whoâs working with AstraZeneca Plc and others on Covid-19 treatments. Scott Gottlieb, former head of the U.S. Food and Drug Administration, also sounded optimistic in a recent interview with Bloomberg News, saying, âIf I had to place one bet on a drug that could be available by the summer and could have activity and could have a profile that I think could change the contours of the infection, it would be the antibody approaches.â
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Enclosures housing VelocImmune mice at Regeneron.Source: Regeneron
âOur technology lets us go in months where it takes others years,â says George Yancopoulos, Regeneronâs co-founder and chief scientist. Yancopoulos, who won a top award in the Westinghouse Science Talent Search in high school (his company took over the contest from Intel Corp. in 2016), is now 60 and one of the richest scientists in the biotech industry, with a net worth of more than $1 billion. During an interview in March at the companyâs headquarters in Tarrytown, N.Y., he wore a Hawaiian shirt, drank a can of soda, and excitedly described how modern antibody technology had evolved over the years from a slow, bespoke process to the industrialized operation that he says Regeneron has perfected.
The company was founded in 1988, went public in 1991, and, as is true of many biotech companies, required many years to get its first drug approved by the FDA. The breakthrough came in 2008, with a compound designed to treat a rare inflammatory disease. Since then, Regeneron has gotten six other drugs on the market. The best known are Eylea, a treatment for macular degeneration, and Dupixent, for severe eczema. A third, a rheumatoid arthritis drug called Kevzara, is being tested on Covid-19 patients; another, the injectable cholesterol-lowering medicine Praluent, cost billions of dollars to develop but hasnât been a commercial success. Yancopoulos himself takes that one.
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Yancopoulos, right, with Christos Kyratsous.Photographer: Samantha Casolari for Bloomberg Businessweek
Regeneron has been conducting research into infectious diseases for about a decade but doesnât yet have an approved drug against any. Its first one could be an Ebola treatment. In 2014, after an outbreak in West Africa, Regeneron devised a combination of antibody drugsâan antibody cocktailâthat was ready for human trials in only 10 months. Last year, after Ebola reappeared in Congo, the drug combination slashed the death rate in half in a large clinical trial, performing the bestof the four treatments tested. It beat ZMapp, a drug that had long been considered the gold-standard treatment for the disease and was featured on the cover of Bloomberg Businessweek in 2014. Regeneronâs Ebola treatment also topped Gileadâs remdesivir, the antiviral drug now being tested in Covid-19 patients. Regeneron has submitted data to the FDA and is waiting for final approval.
The person behind the Ebola success is microbiologist Christos Kyratsous, Regeneronâs 38-year-old vice president for infectious disease research. He and Yancopoulos share the same heritageâGreek Macedonianâand both earned doctorates in microbiology from Columbia. Kyratsous is earnest and soft-spoken, his boss gregarious and fast-talking. Yancopoulos introduces him as âa younger, improved version of me.â
In this crisis, Kyratsous plans to have a drug ready for human trials in just five months. Since January he and his researchers have been working almost all the time on the virus. His grandmother, who lives in Greece, told him she was worried that he was working too muchâevery time she saw him on television, he was wearing the same sweater. He was working 14 hours a day, but she was seeing the same sweater because every station put up the same corporate photo while he was being interviewed.
Antibody treatment has a long history. In 1901, German doctor Emil von Behring won the first Nobel Prize in medicine by showing that âantitoxinsâ found in the blood of animals exposed to diphtheria and tetanus bacterium could be used to treat sick animals and transfer immunity against future infection. Scientists didnât know at the time what these mysterious antitoxins were. They later determined they were blood proteins created by the body to fight infections, and dubbed them antibodies. During World War I, antibody-containing plasma from horses was administered to prevent tetanus in wounded U.S. soldiers. In the midst of the coronavirus pandemic, some hospitals are trying something similar, treating Covid-19 patients with antibody-rich plasma from the blood of those whoâve recovered. This convalescent plasma, as itâs called, may help, but itâs an emergency treatment. It may be hard to scale up, because hospitals have to rely on recovered patients to donate blood. And because the blood contains a mixture of all sorts of antibodies, the more potent ones may be diluted by the others.
The human body can theoretically make hundreds of millions of different antibodies in a personâs lifetime. When a pathogen is introduced, the immune system responds by producing tens of thousands of new antibodies, each of which can bind to a slightly different part of the pathogen and either directly neutralize it or mark it for destruction by other components of the immune system. After a patient recovers from certain diseases, such as measles, highly specific antibodies can remain in the body for years, remembering the pathogen and rendering the person immune. A person infected with the coronavirus will produce antibodies, some much more effective than others. For researchers the goal is to find the specific ones that work best and concentrate them into a powerful medicine.
Antibody drugs are one of several strategies scientists are pursuing against Covid-19. The long-term goal is a vaccine that would teach the immune system to make antibodies against the virus. But testing a vaccine takes timeâlikely 12 to 18 months or longerâand it might not work, or, like the flu shot, be only partly protective. Thatâs why researchers are also hunting for drugs. One possibility is an antiviral drug that could slip into infected cells and interfere with various proteins the virus uses to replicate. These are often administered in pill form, which is ideal. Gileadâs remdesivir, which must be infused, is considered among the most promising of these available options; large-scale human trials should yield results by May. If it or other off-the-shelf drugs donât work, researchers will have to design custom antivirals from scratch, which also takes time. Antibodies occupy a bit of a middle ground between antivirals and vaccines. They have to be infused or injected, and theyâre hard to mass-produce on the same scale as a pill, but the technology allows researchers to move into human trials relatively quickly.
Hereâs where Regeneron and other biotech companies come in. In 1975 scientists devised technology to mass-produce whatâs called a monoclonal antibodyâa single, highly potent antibody that targets exactly one site on one virus. It took decades to perfect the technique, but today many of the worldâs bestselling drugsâparticularly those for cancer and autoimmune diseases such as rheumatoid arthritisâare monoclonal antibodies. Regeneronâs Dupixent is among them.
Monoclonal antibodies are rarely used, however, for infectious disease. Theyâre expensive, often costing $30,000 a year or more, and antibiotics and vaccines have to be cheap to be widely used. And the development process was slow relative to the urgent demands of a pandemic. That has changed. A few years ago, Vancouver-based AbCellera invented a credit card-size âlab on a chipâ device that uses machine vision to test hundreds of thousands of antibody-producing cells at once. The company showed that in only 55 days it could isolate influenza-neutralizing antibodies from human blood that were effective enough to protect mice against an otherwise lethal dose of the virus.
In the current crisis, AbCellera started with blood from a patient whoâd recovered from Covid-19. It received the sample on Feb. 25, began screening antibody-producing cells four days later, and by March 3 had sorted through 5 million of them, finding 500 antibodies that bound to the virusâs spike protein. Then, because AbCellera focuses on discovering drugs, not developing and manufacturing them, its chief executive officer, Carl Hansen, got in touch with a company that does, Eli Lilly. Theyâd already been talking about working together on other antibody drugs. By April, Lilly, with help from the U.S. National Institutes of Health, had narrowed AbCelleraâs original 500 antibodies to 20 that lock onto particular sites on the spikes. After more testing, Lilly expects to select three or four for human trials that could begin as early as July. âWe always hope thereâs just one antibody thatâs really, really great, and we can devote our full manufacturing resources to that,â says Dan Skovronsky, Lillyâs chief scientific officer. But the company is preparing to make more than one.
âIf it turns out our antibody doesnât work and someone elseâs does, probably we would offer capacity for them. And the opposite would be true. No one is looking at this as a moneymaking commercial business. Itâs just how quickly can we helpâ
When pandemic fears were becoming a reality in late January, among the first calls Rick Bright made was to Regeneron CEO Leonard Schleifer. Bright is the director of the Biomedical Advanced Research and Development Authority, or Barda, a division of the U.S. Department of Health and Human Services. Barda has given Regeneron about $300 million over the past five years to work on Ebola, influenza, and other diseases. âThey liked us because we said we could go extremely fast,â Kyratsous says. Bright urged Regeneron to make Covid-19 its top priority. Schleifer immediately agreed.
Kyratsous was already at work. When Chinese researchers shared the gene sequence of the coronavirus in mid-January, his team ordered synthetic DNA for the spike protein for a couple of hundred dollars per sample. They injected the synthetic DNA into genetically engineered mice. No need to collect blood from recovered patients; the mice generate human antibodies in about a month.
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Machinery at Tarrytown used to grow antibodies.Photographer: Samantha Casolari for Bloomberg Businessweek
By the beginning of March, Regeneronâs mice had produced thousands of antibodies that bound to the spike protein on the virus, and by the end of the month, Kyratsous and his team had carefully sorted through them and selected the 40 or so that were most effective. Then Regeneron had to test the antibodies against the actual virus. For that it turned to Matthew Frieman, a coronavirus expert at the University of Maryland School of Medicine in Baltimore and longtime collaborator.
Frieman, who helped Regeneron work on Middle East respiratory syndrome, or MERS, was one of the first researchers in the U.S. to gain access to samples of the live virus when it became available in early February. He has a secure lab and a staff used to handling deadly pathogens, making him a very popular man. Heâs been logging 18-hour days, performing his own drug research and assisting more than a dozen drug and biotech companies as they test possible Covid-19 drugs and vaccines. He spends all day in the lab, heads home to have dinner with his family, and continues to work afterward.
He and his colleagues mix various doses of antibodies with the virus. Then they add African green monkey kidney cells to the mixâa standard type of cell that most viruses can infectâand wait to see if the cells survive. The goal is to find the antibody that binds the tightest to the right place. Itâs easy to tell when it works: Living cells are stained purple, and when they die the color disappears. Several of the Regeneron antibodies appear promising in preliminary tests, Frieman said in a short interview in early April while he was driving home: âEverything is moving just the way it has been supposed to.â
At the same time, scientists around the world have found more than 3,000 gene sequences of the virus, from Asia, Europe, and North America, Kyratsous says, and theyâre not all identical. The virus is evolving. Some parts of the protein spikes so central to finding a treatment are mutating, meaning they could potentially evade an attack. Regeneron is looking specifically for antibodies that latch onto the spots that arenât evolving. âWe want antibodies that bind tightly, neutralizing the virus, and are binding to sites that are not changing very frequently or not at all. Thatâs how weâre screening,â Kyratsous says.
In mid-April, Regeneron chose its final antibodies to testâmore than four and fewer than 10, the company saysâon monkeys. Then a select few will be tested on humans. Concurrently, without waiting for those results, the company is also getting ready for large-scale production. By the end of May âwe will know if there is anything horribly wrong,â Kyratsous says. Because the drugs are targeted so specifically to the virus, he doesnât expect to see any signs of toxicity in the monkeys. If there are none, human trials could get under way by the end of June.
Getting antibodies into trials is one problem. Manufacturing them at an enormous scale is another. Antibodies are far more difficult to produce than traditional medicines, requiring plants that cost hundreds of millions of dollars to build and maintain. These drugs are not simple chemicals like the ones in Tylenol or Prozac or Viagra. Theyâre complex proteins made inside living cells and purified in sterile vials or injectors.
Because most monoclonal antibody drugs are so-called specialty drugs for advanced lung cancer, multiple sclerosis, and other diseases, there is limited capacity globally to make them. âAntibody drugs are fast to develop and reasonably likely to work but inefficient in terms of manufacturing,â says Skovronsky at Lilly. He says companies, nonprofits, and the government are discussing how to share manufacturing plants. âIf it turns out our antibody doesnât work and someone elseâs does, probably we would offer capacity for them. And the opposite would be true,â he says. âNo one is looking at this as a moneymaking commercial business. Itâs just how quickly can we help.â
Regeneron says itâs designed its plants for speed and flexibility. Some biotech companies have customized plants for each of their major drugs. âIf they have 10 products, they have 10 plants,â Yancopoulos says. âWe have one process for all of our drugs. Weâve McDonaldized the manufacturing process.â Regeneron is already retooling one of its major manufacturing plants, in Rensselaer, N.Y., to make Covid-19 antibodies. It may shift much of its other production to Ireland to further increase its capacity for Covid-19 antibody production in New York.
At high doses the drugs might prevent the disease from progressing in hospitalized patients. At lower doses, the same antibodies could work as a prophylactic, conferring immediate but short-term immunity to doctors and other first-line responders. The company says it hopes by August it will be able to produce 200,000 prophylactic doses a month. Already infected patients might require a dose 10 times as strong; the company could make about 20,000 of those a month.
Kyratsous says the long-term goal is to make drugs with what he calls cross-reactive antibodies, which would be effective not just against this coronavirus but against others that have already emergedâand still more that are likely to.
Antibody treatments wonât eliminate the need for a vaccine. They might not work on critically ill patients. And as a prophylactic, the drug would likely have to be given every couple of months. It wouldnât be practical to treat all high-risk people with regular antibody infusions. But the treatments might help communities return to a seminormal state until a vaccine is finally available. âWith Anna Edne
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DONALD TRUMP Published October 3, 2020 8:56am EDT
Trump taking Regeneron drug, Remdesivir therapy for coronavirus diagnosis: ex-WH doctor explains
The president was taken to Walter Reed Medical Center 'out of an abundance of caution' Friday night
President Trump is taking experimental coronavirus drugs Remdesivir and a Regeneron drug after being diagnosed with COVID-19 this week, his former White House physician told "Fox & Friends Weekend."
"The two of those in combination should help clear the virus out of his body much sooner than his body could do it on its own," Dr. Ronny Jackson said Saturday morning.
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The president was taken to Walter Reed National Military Medical Center "out of an abundance of caution" Friday night and is being treated with experimental drugs in response to a compassionate use request.
"The Regeneron product [known as Regeneron-Covid 2 or REGN-COV2] is an antibody product," Trump's former doctor explained.
"They found two particular antibodies in the research they did coming up to developing this product. One of them attaches to the spiked protein and prevents the virus from entering into the host cell, the human cell. So what it does basically is it attaches itself to the virus and it disables the virus where it can't get into the body, into the cells of the body and cause infection, and so that essentially drops the viral count," he said. "Eventually your body clears those viruses."
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The other drug, Remdesivir, he explained, stops viral replication: "So we're blocking the virus that's already in his body and we're preventing the replication of the virus with the Remdesivir," he said.
Jackson, who helped design and build the presidential wing at Walter Reed, predicts that Trump will spend three to four days there.
"I think they'll monitor him and check to make sure the fever is not getting worse and that his symptoms are improving. After a couple of days, I think he will be back to the White House," he said.
Prior to moving to Walter Reed, on Friday afternoon, Dr. Sean P. Conley, the presidentâs physician, released an update on the president's condition.
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âFollowing PCR-confirmation of the presidentâs diagnosis, as a precautionary measure he received a single 8-gram dose of Regeneronâs polyclonal antibody cocktail,â a memo released Friday afternoon by Dr. Sean P. Conley, the presidentâs physician stated. "He completed the infusion without incident.â
"In addition to the polyclonal antibodies, the president has been taking zinc, Vitamin D, famotidine, melatonin and a daily aspirin," Conley said.