Virus World

The first crop of antivirals against SARS-CoV-2 is promising. But new drugs will be needed to counter the looming threat of resistance.  The roll-out of COVID-19 vaccines at the beginning of 2021 marked a key turning point in the fight against the global pandemic. Another major milestone arrived at the end of the year, with the approval of two oral antiviral treatments — molnupiravir and Paxlovid — that promise to reduce the number of COVID-19 hospitalizations and deaths. But as these pills slowly make their way into pharmacies worldwide, researchers are already looking ahead to the drugs that could supersede them. “These are our first-generation antivirals against coronaviruses,” says Sara Cherry, an immunologist at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. Our experience with antivirals against other diseases, like hepatitis C and HIV, proves that “we can do better and better over time”, she adds.  Clinical-trial data showed that molnupiravir, developed by the pharmaceutical firm Merck, based in Kenilworth, New Jersey, and the biotechnology company Ridgeback Biotherapeutics in Miami, Florida, cut hospitalizations and deaths by 30%, compared with people who took placebos. Meanwhile, Paxlovid (nirmatrelvir and ritonavir), made by Pfizer, based in New York City, cut hospitalizations and deaths by 89%. UK regulators approved molnupiravir in November and Paxlovid in December, and US regulators granted emergency authorizations for both drugs in December. Other countries have followed suit with their own approvals, and many are negotiating with the drug makers to buy courses of the drugs or to manufacture their own generic versions. For now, the pills are in short supply. Drug makers are still scaling up production of the antivirals, which are in huge demand to treat the highly transmissible Omicron variant. But when they become more widely available — and if their clinical-trial data is borne out in the real world — the pills will become vital tools to prevent people from becoming seriously ill with COVID-19, says Cherry. It’s too soon to tell whether SARS-CoV-2 is likely to develop any resistance to these first-generation antivirals, says Tim Sheahan, a coronavirologist at the University of North Carolina at Chapel Hill. Although its sky-high rate of replication is a breeding ground for mutations, he says, the virus also causes acute infections that offer relatively little time for resistance-causing mutations to accumulate. But the threat of resistance is particularly severe for ‘monotherapies’ such as molnupiravir and Paxlovid that each target only one part of the virus. That’s why it’s imperative to develop new antivirals aimed at different targets, or ones that can be combined into a single treatment to attack the virus on multiple fronts, says Sheahan. 

A race against resistance

Successful antivirals have typically targeted two key pieces of a virus’s biological machinery, a polymerase and a protease, both of which are essential for viral replication. The current COVID pills are no exception: Paxlovid inhibits SARS-CoV-2’s main protease, whereas molnupiravir tricks its RNA polymerase into incorporating part of the drug into the virus’s RNA, creating so many errors that it cannot survive. A third drug — remdesivir, developed by Gilead, based in Foster City, California — inhibits RNA polymerase, but treatment is expensive and currently requires intravenous infusions over three consecutive days, making it inaccessible to many people.  Unfortunately, molnupiravir’s mode of attack means that it might not be wise to include it in a combination therapy, says Luis Schang, a virologist at Cornell University in Ithaca, New York. If the treatment does not completely wipe out the virus in a patient, some of the RNA errors it creates might inadvertently give the virus resistance against the other drug in the combination. That’s why it’s a key priority for researchers to find an accessible drug that effectively blocks the virus’s RNA polymerase, he says, which could be used in partnership with a protease inhibitor such as Paxlovid. One option may be an oral version of remdesivir, which Gilead is currently testing. Other antiviral drug candidates are slowly working their way through the clinical-trial pipeline, says Carl Dieffenbach, director of the division of AIDS at the US National Institute of Allergy and Infectious Diseases (NIAID). He says that one promising candidate is a protease inhibitor, developed by Shionogi & Company, based in Osaka, Japan, and Hokkaido University in Japan, that is currently in phase II/III clinical trials in Asia. The candidate targets the same protease as Paxlovid but would only require patients to take a single pill each day.  That simpler regimen could help to avert the rise of resistance, Cherry says. Unfinished treatments can hasten drug resistance by allowing the virus to develop defences against the drug while it continues multiplying and wreaking havoc in the body. Both molnupiravir and Paxlovid consist of several pills that must be taken twice a day for five consecutive days. “The second you have people taking something multiple times a day when they’re sick is when you have issues with compliance,” Cherry says.

Target practice

Researchers should also develop treatments that target other parts of the virus, Schang says. “This time we got lucky with a virus that encodes both a polymerase and a protease, and here we are two years later with only a suboptimal arsenal,” he says. “We really have to identify and validate new targets for antivirals so that when the next [pandemic] happens, we have a much broader pipeline to choose from.”  Other potential targets include a different protease in SARS-CoV-2 called PLpro, and an enzyme called methyltransferase that stabilizes the virus’s RNA, says Matt Hall, the director of the early translation branch at the US National Center for Advancing Translational Sciences (NCATS). Clear Creek Bio, a biotechnology firm based in Cambridge, Massachusetts, announced on 6 January that it will collaborate with NCATS to develop an oral drug targeting the PLpro enzyme. Dieffenbach says that researchers would ideally like to identify targets that are common to entire families of viruses and inhibit them with a single drug. That would potentially allow public-health officials to rapidly deploy an effective antiviral the next time a novel virus with pandemic potential emerges. Developing such broad-spectrum drugs will take significant public and private investment, and the cooperation of pharmaceutical companies, says Hall. Calls for such efforts were not heeded in the wake of the 2003 SARS-CoV outbreak, he adds, but the latest pandemic has underlined the need for action. Last year, the United States appropriated US$1.2 billion to NIAID to launch the Antiviral Drug Discovery Centers for Pathogens of Pandemic Concern, which will fund basic research on developing antivirals for seven virus families. Hall says this gives him hope that antiviral research will continue even as the COVID-19 pandemic wanes. But all antivirals face an inherent limitation, says Dieffenbach: they must be taken within days of infection to stop a virus from proliferating. Antivirals are only effective if people acknowledge that they might be ill, and can access tests that provide a timely diagnosis. “We can build the best drugs in the world, but if people don’t understand that they have to get on board quickly, they’re not going to do any good,” says Dieffenbach. “Pills do not take themselves.”

Published in Nature (Jan. 22, 2022):

https://doi.org/10.1038/d41586-022-00112-8 

New late-stage trial data show Regeneron and Roche's antibody cocktail against COVID-19 cut hospitalisation or death by 70% versus a placebo in non-hospitalised patients, the Swiss drugmaker said on Tuesday. The shot, consisting of casirivimab and imdevimab antibodies developed by Regeneron with financial help from the U.S. government, also met all key secondary endpoints in the phase III trial with 4,567 participants, including reducing symptom duration to 10 days from 14, Roche said.  Roche, which is making the drug at plants in California and which is responsible for sales outside the United States, and Regeneron are expecting hundreds of millions in sales in 2021 from the drug, including $260 million alone to the U.S. government in the first quarter. 

“New infections continue to rise globally with over three million reported cases last week, so this investigational antibody cocktail may offer hope as a potential new therapy to high-risk patients - particularly in light of recent evidence showing that casirivimab and imdevimab together retain activity against key emerging variants,” Roche Chief Medical Officer Levi Garraway said.  Roche has said that it and Regeneron can produce more than 2 million doses annually. The cocktail, which data previously showed has been effective against variants, has emergency approval in the United States, and has been authorized in Europe for use in non-hospitalised patients. Former U.S. President Donald Trump got the treatment when he was infected with COVID-19.

Roche's Press Release (March 23, 2021):

https://www.roche.com/media/releases/med-cor-2021-03-23.htm

The saga of COVID-19 antibody R&D continues as the REGN-COV2 antibody cocktail used by President Donald Trump and touted as a cure has been hit by safety worries as it continues to push for an FDA emergency authorization. The cocktail, which has been erroneously called “Regeneron,” is currently in a series of tests including for patients with COVID-19 that are currently hospitalized. But Friday morning, the independent data monitoring committee (IDMC) told Regeneron safety concerns will need to see it roll back the sickest patients on the test.  It said: “Based on a potential safety signal and an unfavorable risk/benefit profile at this time, the IDMC recommends further enrollment of patients requiring high-flow oxygen or mechanical ventilation be placed on hold pending collection and analysis of further data on patients already enrolled.

It did not give details on what the safety signal was. The news hit shares, which were in the red by 2.6% premarket when the news first hit The IDMC did, however, say that the biopharma can continue enrollment of hospitalized patients who need either no or low-flow oxygen as the “risk/benefit remains acceptable in these cohorts.” It can also continue work of the outpatient trial “without modification.”  The FDA is currently assessing the cocktails for a speedy emergency use authorization nod, specifically in mild to moderate outpatients at high risk for poor outcomes. It’s not clear how this news will impact this process. This comes only a few days after the therapy showed it reduced COVID-19 related medical visits by 57% in early data.

A mix of ultrapotent antibodies from recovered COVID-19 patients has been shown to recognize and lock down the infection machinery of the pandemic coronavirus and keep it from entering cells. Each of the antibody types performs these overlapping tasks slightly differently. Low doses of these antibodies, individually or as a cocktail, were also shown to protect hamsters from infection when exposed to the coronavirus by preventing it from replicating in their lungs. An advantage of such cocktails is that they might also prevent the natural mutant forms of the virus that arose during this pandemic to escape treatment. As some variants in the infection machinery have already been discovered during the coronavirus pandemic, using a mix of antibodies allows for neutralization of a broad spectrum of such viral variants. In addition to preventing virus entry into host cells, the presence of the antibodies also seems to set off the infection-fighting actions of other immune cells, which arrive to clear out the virus. "We believe that leveraging multiple, distinct, complementary mechanisms of action could provide additional benefits for clinical applications," the researchers noted.

The researchers determined how the antibodies worked on a molecular level through cryo-electron microscopy studies of the resulting changes in the configuration of the virus infection machinery. Besides directly preventing interactions with the host receptor, one of the two discovered antibodies locks the infection machinery in an inactive conformation, meaning it could not fuse with the host membrane on the surface of the cell. If unable to fuse, the coronavirus cannot break in and deliver its RNA to commandeer the cell.  The findings of this research are reported Sept. 24 in a rapid release paper in Science. Here is the paper. The senior authors were Dr. Katja Fink of Vir Biotechnology and Dr. David Veesler, associate professor of biochemistry at the University of Washington School of Medicine. Veesler has studied the molecular structure and infection mechanisms of a variety of coronaviruses and other viruses. The lead authors were M. Alejandra Tortorici of the UW Department of Biochemistry and the Institut Pasteur in Paris, and Martina Beltramello of Humab BioMed, a subsidiary of Vir Biotechnology in Switzerland. Researchers from Washington University in St Louis, Rega Institute in Belgium, the University of Milan, Italy, and the University of Texas in Dallas also collaborated on the research.

Efficient therapeutic options are needed to control the spread of SARS-CoV-2 that has caused more than 978,000 fatalities worldwide. While the world awaits approved vaccines, pharmaceuticals to prevent or treat infections from the pandemic coronavirus are being sought that might be quicker to develop and test. These might both address the gap until vaccines are widely distributed, and still be needed for use after vaccines are available. "Our results pave the way to implement antibody cocktails for prophylaxis or therapy that might have the advantage of circumventing or limiting the emergence of viral escape mutants," the researchers noted. The antibody cocktail in their study needs to undergo trials in humans to determine safety and effectiveness.

Original study published in Science (Sept. 24, 2020):

https://doi.org/10.1126/science.abe3354

The studies were run on a total of 36 rhesus macaques and 50 hamsters. The company is careful to caution that positive animal studies do not guarantee success in humans. In early July, Regeneron Pharmaceuticals, with the U.S. National Institute of Allergy and Infectious Diseases (NIAID), announced they were launching Phase III trials of REGN-COV-2, the company’s two-antibody cocktail to treat and prevent COVID-19. Although those results of those trials are still pending, the company issued a scientific article, not yet peer-reviewed, that shows the cocktail was able to “almost completely block establishment of virus infection,” in rhesus macaques and hamsters. Using its proprietary VelocImmune mice, Regeneron screened thousands of fully-human antibodies. The mice have been genetically modified to have a human immune system. They also evaluated antibodies isolated from people who have recovered from COVID-19. They then chose the two most potent, non-competing antibodies that were most effective at neutralizing SARS-CoV-2, the virus that causes COVID-19. They then scaled up the dual-antibody cocktail for clinical use with the company’s own VelociMab and manufacturing capabilities. The two antibodies bind non-competitively to the receptor binding domain of the virus’s spike (S) protein. This decreases the ability of mutant viruses to avoid treatment and protects against spike variants that have evolved in the human population. On June 11, the company announced the publication of two scientific articles describing the effectiveness of REGN-COV-2 in the journal Science. The first paper was, “Studies in humanized mice and convalescent humans yield a SARS-COV-2 antibody cocktail.”

In the latest animal study paper, the authors said the cocktail in monkeys and hamsters demonstrated “that REGEN-COV-2 can greatly reduce virus load in lower and upper airway and decrease virus-induced pathological sequelae when administered prophylactically or therapeutically. Our results provide evidence of the therapeutic potential of this antibody cocktail.” Essentially, the study took two approaches. One was to infect animals with the virus, then dose them with the antibody cocktail to see if it could halt the infection. It appeared to do this successfully. 

The second approach was to dose the animals with the antibody cocktail, then infect them with the virus. This also appeared to prevent infection. It’s important to note that the antibody cocktail is not a vaccine. Therapeutic antibodies such as these do not have long-range effects, although they may last several months. The studies were run on a total of 36 rhesus macaques and 50 hamsters. The company is careful to caution that positive animal studies do not guarantee success in humans. The human trials have already started. There are specifically two trials. A Phase III trial will study if REGN-COV-2 can prevent infection in uninfected people who have had close exposure to a COVID-19 patient. The drug has also been advanced into the Phase II/III portion of two adaptive Phase I/II/III trials evaluating the cocktail in treating hospitalized and non-hospitalized patients with COVID-19....

Preprint available at bioRxiv (August 3, 2020):

https://doi.org/10.1101/2020.08.02.233320

Regeneron said that a single dose of its antibody cocktail REGEN-COV reduced the risk for COVID-19 by nearly 82% up to 8 months after administration in a phase 3 trial. REGEN-COV, which contains 600 mg each of the monoclonal antibodies casirivimab and imdevimab, was authorized for emergency use by the FDA in November 2020 for the treatment of mild to moderate COVID-19 in high-risk patients. The FDA expanded the emergency use authorization in July to include post-exposure prophylaxis.  Trial results announced Monday by Regeneron showed that, compared with placebo, people who received a single dose of REGEN-COV had an 81.6% reduced risk for developing COVID-19 during a 2-to-8-month follow-up period (95% CI, 59.8%-91.6%) and an 81.5% reduced risk for developing COVID-19 at any time during the 8 months after receiving REGEN-COV (95% CI, 70.6%-88.4%). Myron S. Cohen, MD, who leads the monoclonal antibody efforts for the NIH-sponsored COVID Prevention Network and is director of the Institute for Global Health & Infectious Diseases at the University of North Carolina at Chapel Hill, said the findings “demonstrate how a single dose of REGEN-COV can help protect people from COVID-19 for many months after administration.” "These results demonstrate that REGEN-COV has the potential to provide long-lasting immunity from SARS-CoV-2 infection, a result particularly important to those who do not respond to COVID-19 vaccines, including people who are immunocompromised,” Cohen said.

Regeneron said the data build on previously published findings in The New England Journal of Medicine, which reported a risk reduction of 81.4% in the first month. The newly announced findings were from an 8-month follow-up that continued to compare outcomes from more than 1,600 people assigned to receive a single dose of the cocktail or placebo. In all, seven people in the treatment arm and 38 in the placebo arm developed COVID-19 within 2 to 8 months. George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron, said the data “add to the increasing body of evidence supporting the use of REGEN-COV to prevent COVID-19 in uninfected individuals.” “With infections still occurring despite widespread vaccination, the immunocompromised face an ongoing risk of encountering the virus during their daily lives,” Yancopoulos said in a statement. “We intend to rapidly share these additional data with regulatory authorities to help those in most need of protection from COVID-19.”

Regeneron's therapy is part of a class of treatments known as monoclonal antibodies, which are made to act as immune cells that scientists hope can fight infections. The Food and Drug Administration on Saturday granted an emergency use authorization for Regeneron’s Covid-19 antibody treatment, the experimental therapy given to President Donald Trump when he contracted the coronavirus in October. Regeneron submitted an emergency use application that month after preclinical studies showed that the therapy, called REGN-COV2, reduced the amount of virus and associated damage in the lungs of non-human primates. The company said trial data also shows the drug reduces medical visits in patients with mild-to-moderate Covid-19. “The FDA remains committed to advancing the nation’s public health during this unprecedented pandemic. Authorizing these monoclonal antibody therapies may help outpatients avoid hospitalization and alleviate the burden on our health care system,” said FDA Commissioner Stephen M. Hahn. Regeneron’s therapy is part of a class of treatments known as monoclonal antibodies, which are made to act as immune cells that scientists hope can fight infections. Monoclonal antibody treatments gained widespread attention after news that Trump received Regeneron’s antibody cocktail. As Trump’s health improved, he touted it as a “cure.” But Regeneron’s CEO, Dr. Leonard Schleifer, has stressed that more testing is required.

“Some people don’t know how to define therapeutic. I view it different. It’s a cure,” Trump said in a video posted Oct. 7 on Twitter. “For me, I walked in. I didn’t feel good. A short 24 hours later, I was feeling great. I wanted to get out of the hospital. And that’s what I want for everybody. I want everybody to be given the same treatment as your president because I feel great.” Regeneron’s authorization comes after the FDA announced on Nov. 9 that it had authorized Eli Lilly’s antibody treatment – called bamlanivimab –for people newly infected with Covid and are at risk of developing a severe form of the disease. Officials said the treatment shouldn’t be used for hospitalized patients because there is no data to show the drug is helpful at that stage of the disease. The authorization will expand the number of drugs at doctors’ disposal to fight the virus, which continues to rapidly spread across the United States and other parts of the world. Before the authorization, people could only get the drug as part of an FDA program that gives some patients limited access to investigational medical products. Gilead Sciences’ antiviral drug remdesivir is the first and only fully approved treatment in the U.S. for Covid.

FDA Authorization Letter (Nov. 21, 2020):

https://www.fda.gov/media/143891/download

Experts caution more data from larger trials will be needed to know how potentially beneficial monoclonal antibodies are. New data from the biotechnology firm Regeneron seem likely to add to the excitement about drugs called monoclonal antibodies as treatments for Covid-19, but experts caution more data will be needed to know how potentially beneficial the medicines are.  A high dose of the company’s antibody cocktail, REGN-COV2, led levels of the virus to decrease more quickly in infected, non-hospitalized patients, potentially indicating the treatment may help them get better, Regeneron reported Tuesday via press release. Full results will be published at a later date.  “There’s nothing bad about these results, you just can’t say much about how transformative this is going to be,” said Eric Topol, director of the Scripps Research Translational Institute. As with data from a similar antibody, developed by Eli Lilly, he warned that the data so far should not be enough for the Food and Drug Administration to grant an emergency use authorization.   “This doesn’t cut it, but it’s moving in the right direction, that’s for sure,” Topol said. In a notable finding, the data seem to show that the antibody had a bigger effect in patients who tested positive for SARS-CoV-2 but had not created high levels of their own antibodies against the virus. In this group, even a lower dose of the Regeneron antibodies seemed to result in patients getting better faster.

The data add to the early results from Eli Lilly, which showed a reduction in virus levels for patients at some doses and a tantalizing hint that the treatment might help keep patients out of the hospital.  Monoclonal antibodies are synthetic versions of one of the immune system’s own weapons against invaders. From the start of the pandemic, some experts have been most hopeful about this technology to create new medicines to fight SARS-CoV-2, the virus that causes Covid-19. But that potential could be limited by the ability to manufacture large quantities of the treatments. Regeneron has reached an agreement with Roche, the Swiss drug giant, to increase its production capacity. Experts said longer studies, which are ongoing, will be needed to really know if the antibody treatments make patients better. “We are highly encouraged by the robust and consistent nature of these initial data, as well as the emerging well-tolerated safety profile, and we have begun discussing our findings with regulatory authorities while continuing our ongoing trials,” said George Yancopoulos, Regeneron’s chief scientific officer. 

The data are from a 275-patient portion of Regeneron’s study testing REGN-COV2 in patients who have tested positive for Covid-19 but who are not in the hospital. Patients received either placebo, 2.4 grams of REGN-COV2, or 8 grams of REGN-COV2. (The antibody cocktail is delivered intravenously.) Those who received the high dose saw viral levels decrease by 0.60 log10 copies of the virus per milliliter compared to placebo after seven days, a result that was statistically significant. In the lower dose, there was a 0.23 log10 reduction, which was not statistically significant. Regeneron did not give the total amount of virus detected in its press release. At the beginning of the study, Regeneron tested patients not only to see if they had SARS-CoV-2, but also to see if they created their own antibodies against the virus. The company found that 45% of patients had created antibodies, 41% had not, and 14% had unclear results. Those without antibodies had higher levels of virus in swabs from their noses from the start. And those who had created their own antibodies got better much faster. Patients with their own antibodies in the placebo group saw symptoms disappear in seven days, while in those whom antibodies were not detected, it took 13 days for symptoms to go away. Giving the patients Regeneron’s synthetic antibody had a far greater effect on the amount of virus detected in those who did not have an antibody response before treatment. There was a reduction of 0.6 log10 copies/mL in the patients who received the high dose, and 0.51 in those who received the low dose, both of them statistically significant. The reductions were also greater in patients who had higher levels of virus. And in those patients who did not have detectable antibodies at the study’s outset, Regeneron’s antibody cocktail improved symptoms. In this group, symptoms were alleviated in 13 days on placebo, eight days in the high-dose group, and six days in the low-dose group.  Among the 275 patients for whom data are being reported, 50% were Hispanic, 14% were African American, and the rest of the racial breakdown was not disclosed. On average, they were 45 years old. Forty-nine percent of participants were male and 51% were female...

Regeneron's Press Release:

https://investor.regeneron.com/news-releases/news-release-details/regenerons-regn-cov2-antibody-cocktail-reduced-viral-levels-and 

The world's largest randomised trial of potential medicines for COVID-19 is to add Regeneron's experimental antiviral antibody cocktail REGN-COV2 to the drugs it is testing in patients hospitalised with the disease. The UK RECOVERY trial, which has been testing a range of potential COVID-19 treatments since it began in April, will compare the effects of adding REGN-COV2 - a lab-manufactured monoclonal antibody - to standard care. “This is the first drug actually designed for this disease,” said Martin Landray, a professor of medicine & epidemiology at Oxford University who is co-leading the trial. “There are lots of good reasons for thinking this might be really quite a powerful treatment,” he told Reuters in an interview. The addition of Regeneron’s drug to the RECOVERY trial comes amid growing hopes that monoclonal antibodies may emerge as effective ways to treat COVID-19.  Until now, the RECOVERY trial had mostly been studying whether existing drugs could be re-purposed to tackle the new disease, and it has already found answers on a number of them.

In June and September, trial results showed that widely used steroids such as dexamethasone and hydrocortisone were able to reduce death rates among severely-ill COVID-19 patients.  Also in June, RECOVERY trial results showed that the anti-malarial drug hydroxychloroquine, once touted by U.S. President Donald Trump as a potential “game changer” in the pandemic, was of no benefit in treating COVID-19 patients.  Regeneron’s REGN-COV2 cocktail, which the company is already testing in late-stage clinical trials in people, combines one Regeneron-made antibody and a second antibody isolated from people who have recovered after being infected with COVID-19.  The combination is designed to bind to the spike protein used by the new coronavirus to gain access to human cells, limiting the virus’s ability to escape.  Regeneron developed the biological drug before linking up with Roche ROG.S to expand its manufacturing capacity in hopes of meeting global demand, should the medicine prove effective. Regeneron would handle U.S. sales, with Roche selling the medicine around the world.

Landray said his team had secured enough supply of the drug so that up to “several thousand” patients could be given it in the trial and compared with several thousand controls. “Given that the second phase (of COVID-19 infections in the UK) seems to be coming now, it is a really good time to be starting this,” he said. The United States already has a $450 million deal for the cocktail in place, under the terms of which Regeneron will sell it around 70,000 to 300,000 potential treatment doses or 420,000 to 1.3 million prevention doses of REGN-COV2. Data is due later this month, Regeneron has said.  Alongside Regeneron, Eli Lilly LLY.N, working with biotech firm AbCellera, is seen as a leading contender in the antibody race. In August it started testing whether its antibody can prevent COVID-19 infections in nursing homes. A separate trial testing the compound on recently diagnosed COVID patients may yield initial data in September or shortly after. GlaxoSmithKline GSK.L and partner Vir Biotechnology VIR.O also began testing an experimental antibody on newly diagnosed COVID-19 patients late last month. AstraZeneca AZN.L is for now testing its antibody-based cocktail on healthy volunteers for tolerability.