Even as vaccines are hailed as our best hope against the coronavirus, dozens of scientific groups are working on an alternate defense: monoclonal antibodies. These therapies shot to prominence just this month after President Trump got an infusion of an antibody cocktail made by Regeneron and credited it for his apparent recovery, even calling it a “cure.”
Monoclonal antibodies are distilled from the blood of patients who have recovered from the virus. Ideally, antibodies infused early in the course of infection — or even before exposure, as a preventive — may provide swift immunity.
An enthusiastic Mr. Trump has promised to distribute these experimental drugs free to anyone who needs them. But they are difficult and expensive to produce. At the moment, Regeneron has enough to treat only 50,000 patients; the supply is unlikely to exceed a few million doses in the foreseeable future.
Dozens of companies and academic groups are racing to develop antibody therapies. Already Regeneron and the drug company Eli Lilly have requested emergency use authorizations for their products from the Food and Drug Administration.
These drug companies have the long experience and deep pockets needed to win the race for a powerful antibody treatment. But some scientists are betting on a dark horse: Prometheus, a ragtag group of scientists who are months behind in the competition — and yet may ultimately deliver the most powerful antibody.
Prometheus is a collaboration between academic labs, the United States Army Medical Research Institute of Infectious Diseases, and a New Hampshire-based antibody company called Adimab.
The group’s antibody is not expected to be in human trials until late December, but it may be worth the wait. Unlike the antibodies made by Regeneron and Eli Lilly, which fade in the body within weeks, Prometheus’s antibody aims to be effective for up to six months.
“A single dose goes a long way, meaning we can treat more people,” said Kartik Chandran, a virologist at Albert Einstein College of Medicine and the group’s leader.
In mice and laboratory tests, Prometheus’s antibody protects against not just the coronavirus, but also the SARS virus and similar bat viruses — suggesting that the treatment may protect against any coronaviruses emerging in the future.
Among scientists, Dr. Chandran and Prometheus are famous for careful and clever work that has unearthed critical insights into deadly pathogens. While working on Ebola, for example, the team discovered a new entryway into human cells used by the virus, and used that information to design an antibody combination that works against all major strains of Ebola.
“They do very innovative stuff,” said Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York. “If they find something cool, they dig deep.”
Outgunned, at First
Antibodies are as variable as the people who produce them. Some antibodies are weaker than others; some target a different part of the coronavirus than others; and some are powerful protectors, while a small number may even turn against the body, as they do in autoimmune diseases.
Monoclonal antibodies are artificially synthesized copies of the most effective antibodies produced naturally by patients. In late February, AbCellera fished out an apparent winner from among 550 antibodies drawn from the blood of an infected patient. Barely three months later, partner Eli Lilly began the first trial of a synthesized version in patients.
Regeneron, which has a $450 million contract from the federal government to develop its treatment, was not far behind. Its drug is a cocktail of two antibodies. One was discovered in a patient in Singapore, while the other was made using a synthetic viral snippet in mice.
On Sept. 29, days before Mr. Trump received his infusion, Regeneron announced that this cocktail seemed particularly helpful for people who did not produce enough antibodies of their own against the coronavirus.
Both Regeneron and Eli Lilly have stockpiled tens of thousands of doses of their drugs, rather than wait for F.D.A. approval.
Without the resources or reach of these bigger companies, Prometheus has lagged behind.
With a $22 million federal grant, the group had been developing therapies for deadly viruses like the one causing Crimean-Congo hemorrhagic fever and various hantaviruses. But in the earliest days of the pandemic, the group was not able to take on the coronavirus.
“We had all of the technology, all the tools ready to go,” Dr. Chandran said. “The only thing we didn’t have was a patient sample.”
Most of those samples had been handed to large pharmaceutical companies by the federal government. So the Prometheus researchers took an unusual tack, instead relying on blood from a survivor of the 2003 SARS outbreak. (The coronavirus is a close cousin.)
These scientists had experience on their side. One teammate, Jason McLellan of the University of Texas at Austin, was an expert in coronaviruses; another, John Dye of the Army’s infectious diseases institute, had done pioneering work on Ebola antibodies.
In March, Dr. McLellan was the first to publish the structure of the new coronavirus in the journal Science. He supplied Adimab, Prometheus’s commercial arm, with the pathogen’s “spike protein,” a protrusion on its surface that latches on to human cells and breaks in.
Using the protein as a lure, Adimab snared 200 antibodies from the patient sample. Dr. Chandran screened those antibodies against a proxy for the coronavirus, and Dr. Dye against the live virus in a high-safety laboratory.
Together, they refined the list to seven antibodies that recognized both SARS and the new coronavirus. Scientists at Adimab then enhanced the neutralizing power of one antibody by about 100-fold, yet retaining its effectiveness against all SARS family coronaviruses.
“The goal was to do what we did with Ebola — find an antibody that not only works against the current virus, but also past viruses that might re-emerge, like SARS, and future viruses that exist already in the bat reservoir,” said Laura Walker, an immunologist and an associate director at Adimab.
“If you had something on Day 1 to prevent all of this from happening in the first place, that would be a very good thing.”
‘Too Complicated to Make’
Monoclonal antibodies can rapidly prevent the virus from taking hold in the body — say, in the residents of a nursing home with one confirmed case of infection. Vaccines, which require weeks to unspool an immune response, are useless in such a scenario.
But limited production capacity is likely to keep monoclonal antibodies out of reach for most people.
Regeneron expects to have enough of its cocktail to treat 300,000 patients within the next few months. The company may eventually produce about two million doses annually worldwide in partnership with Roche. Eli Lilly hopes to have 100,000 doses available later this month.
Even dozens of companies manufacturing antibodies could not produce the billions of doses required for the world — or just the minimum estimate of 25 million doses needed for Covid-19 patients and high-risk people in the United States alone.
And it’s not clear how quickly manufacturing capacity could be scaled up. For one, the treatments are made in specialized facilities with ingredients — sterile vials, protein resins, culture media — needed to make other antibodies and vaccines, as well.
“It’s a finite capacity, and there are only so many things you can do to try to increase that capacity,” said John Kokai-Kun, the director of external scientific collaboration at U.S. Pharmacopeia, an organization that monitors manufacturing quality.
The antibodies are also expensive to produce. Some cost up to $200,000 — even the cheapest cost about $15,000 — per year of treatment, making them unattainable for all but the richest of countries, according to a report released in August.
“I don’t see monoclonal antibodies being at large-scale use in the public,” Dr. Kokai-Kun said. “They’re just too complicated to make and too expensive to really be effective in that regard.”
Like vaccines, the antibodies have to be injected, and the amounts, which are calibrated to a person’s weight, can be significant. (Mr. Trump received eight grams — vaccine doses tend to be in micrograms or even nanograms.) The protection wanes after just a few weeks.
“That puts a strain on your manufacturing infrastructure already to make the kinds of doses that we think are going to be required worldwide,” said Andrew Adams, a vice president at Eli Lilly. “We have to start thinking about the populations that we should prioritize.”
Dozens more companies, and scores of academic groups — including many in China — are in the hunt for antibodies against the coronavirus. Given the urgent need, some may combine their resources — as some did at the height of the AIDS pandemic — to keep prices affordable for low- and middle-income countries.
In July, six companies, including Eli Lilly and AstraZeneca, successfully appealed to the Department of Justice to allow them to share information about manufacturing facilities, raw materials and supplies without violating antitrust laws.
Prometheus is testing its first antibody in isolation, but plans to create a cocktail with a second antibody that is specific to the new coronavirus. The two antibodies have to be chosen carefully — to complement each other or, at the very least, to not hinder each other, because they bind within the same small piece of the virus.
But each additional antibody requires more manufacturing capacity, increasing time and cost. For now, the first priority is a single powerhouse antibody that broadly protects against bat-origin coronaviruses, Dr. Chandran said.
“We believe it’s a matter of when, and not if, the next coronavirus spillover happens.”
Apollo Board Will Review Leon Black’s Ties to Jeffrey Epstein
The billionaire Leon Black’s decades-long relationship with the convicted sex offender Jeffrey Epstein will be reviewed by a group of board members at the private equity firm he leads, Apollo Global Management.
A spokeswoman for Apollo said Tuesday night that Mr. Black requested the review by members of the firm’s conflicts committee during a regularly scheduled board meeting.
Mr. Black asked for the review a little more than a week after The New York Times reported that he had wired at least $50 million in fees and donations to entities affiliated with Mr. Epstein in the U.S. Virgin Islands from 2012 to 2017.
Shares of Apollo have fallen more than 13 percent since the report was published. The firm reports quarterly earnings on Oct. 29.
In asking for the review, Mr. Black, an Apollo co-founder and its chief executive, said an independent review was in “the best interests” of Apollo, its employees, shareholders and limited partners. The board committee retained the law firm Dechert LLP to conduct the review.
Mr. Black and Apollo have repeatedly said that Mr. Epstein did no work for the firm, which counts some of the biggest public pensions in the world among its investors.
In a letter to investors after the Times report, Mr. Black said he had not been accused of any wrongdoing. He said he had paid millions in fees to Mr. Epstein for advice, mainly on estate planning.
Mr. Epstein died in custody in August 2019 after federal prosecutors in Manhattan had accused him of engaging in sex trafficking with underage girls and young women. His death was ruled a suicide.
Mr. Black’s letter said he regretted his dealings with Mr. Epstein but had been unaware of the activities that led to the most recent criminal charges against him.
Mr. Epstein pleaded guilty to a charge of soliciting prostitution from an underage girl in Florida in 2008, a case that required him to register as a sex offender. Mr. Black’s letter offered few details about the nature of the work that Mr. Epstein had provided for him in the years that followed. Mr. Epstein, a college dropout who styled himself a financial guru to the very wealthy, had no particular expertise in tax and estate planning.
Mr. Black is worth about $9 billion and is one of the wealthiest executives on Wall Street. He has an art collection estimated to be worth $1 billion and serves as chairman of the board of the Museum of Modern Art.
Mr. Black asked for the review because he wants an independent analysis to support his statement that he did nothing wrong and all the fees paid were legitimate, according to a person briefed on the matter who was not authorized to speak publicly.
The board’s review was first reported by The Wall Street Journal.
Disneyland, Other California Theme Parks, Get Rules for Reopening
California health officials issued long-awaited guidance for reopening theme parks in the state on Tuesday, setting targets for when attractions like Disneyland Resort, in Anaheim, and Universal Studios Hollywood, in Los Angeles, can open their doors. For the big parks, it could be a long road: their counties must reach the least-restrictive “yellow” tier of the state’s four-tier Covid-19 economic-reopening plan.
In terms of coronavirus cases, Orange County, home to Disneyland, is currently in the “red,” or second, tier and Los Angeles County, Universal Studios’ location, is currently in the most restrictive “purple” tier. It could be months before either county meets the guidelines for the “yellow” tier, which requires there be fewer than one case a day per 100,000 residents and a testing positivity rate of less than 2 percent. The parks have been closed since March.
The secretary of California’s Health and Human Services Agency, Dr. Mark Ghaly, issued the guidelines in a video conference on Tuesday and said that he believes that the tier guidelines can be reached. He said that San Francisco County had already met them.
“There’s lots of work we can do together — both state, local, business leaders, community leaders, individuals — to do what we can to make sure that we reduce transmission throughout our county and there is a path forward there,” Dr. Ghaly said. “We do not know when, but we do know how, and I think we’ll continue to put in the hard work to get us there one county at a time.”
However, Disneyland Resort’s president, Ken Potrock, said in a statement that the guidelines are “arbitrary” and “unworkable.”
“We have proven that we can responsibly reopen, with science-based health and safety protocols strictly enforced at our theme park properties around the world,” Mr. Potrock said. “Nevertheless, the State of California continues to ignore this fact, instead mandating arbitrary guidelines that it knows are unworkable and that hold us to a standard vastly different from other reopened businesses and state-operated facilities.”
When parks do reopen, they will have to implement a reservation system allowing guests to book visits ahead of time. They will also have to screen guests for symptoms and mandate masks everywhere inside the park, except when people are eating and drinking. Larger parks, like Disneyworld and Universal Studios Hollywood, will have to limit capacity to 25 percent.
Smaller parks in California can reopen when they reach the third or “orange” tier. They will be allowed to have up to 25 percent capacity or 500 guests, depending on which number is less, and only people from the park’s home county will be allowed to visit.
Disney World, the company’s Orlando, Fla., park, reopened in July with strict social distancing and capacity requirements and there have been no major outbreaks of the coronavirus associated with the park. But low attendance has led the company to start layoffs there. The pandemic has cut off many of Disney’s lines of business, including films, theater productions and cruises. Disneyland generated an estimated $3.8 billion in revenue last year, according to Michael Nathanson, a media analyst.
On Monday, a coalition of unions representing thousands of workers at Disneyland told California Gov. Gavin Newsom that it is generally satisfied with the health measures laid out by the company for operating safely.
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Trump Records Shed New Light on Chinese Business Pursuits
President Trump and his allies have tried to paint the Democratic nominee, Joseph R. Biden Jr., as soft on China, in part by pointing to his son’s business dealings there.
Senate Republicans produced a report asserting, among other things, that Mr. Biden’s son Hunter “opened a bank account” with a Chinese businessman, part of what it said were his numerous connections to “foreign nationals and foreign governments across the globe.”
But Mr. Trump’s own business history is filled with overseas financial deals, and some have involved the Chinese state. He spent a decade unsuccessfully pursuing projects in China, operating an office there during his first run for president and forging a partnership with a major government-controlled company.
And it turns out that China is one of only three foreign nations — the others are Britain and Ireland — where Mr. Trump maintains a bank account, according to an analysis of the president’s tax records, which were obtained by The New York Times. The foreign accounts do not show up on Mr. Trump’s public financial disclosures, where he must list personal assets, because they are held under corporate names. The identities of the financial institutions are not clear.
The Chinese account is controlled by Trump International Hotels Management L.L.C., which the tax records show paid $188,561 in taxes in China while pursuing licensing deals there from 2013 to 2015.
The tax records do not include details on how much money may have passed through the overseas accounts, though the Internal Revenue Service does require filers to report the portion of their income derived from other countries. The British and Irish accounts are held by companies that operate Mr. Trump’s golf courses in Scotland and Ireland, which regularly report millions of dollars in revenue from those countries. Trump International Hotels Management reported just a few thousand dollars from China.
In response to questions from The Times, Alan Garten, a lawyer for the Trump Organization, said the company had “opened an account with a Chinese bank having offices in the United States in order to pay the local taxes” associated with efforts to do business there. He said the company had opened the account after establishing an office in China “to explore the potential for hotel deals in Asia.”
“No deals, transactions or other business activities ever materialized and, since 2015, the office has remained inactive,” Mr. Garten said. “Though the bank account remains open, it has never been used for any other purpose.”
China continues to be an issue in the 2020 presidential campaign, from the president’s trade war to his barbs over the origin of the coronavirus pandemic. His campaign has tried to portray Mr. Biden as a “puppet” of China who, as vice president, misread the dangers posed by its growing power. Mr. Trump has also sought to tar his opponent with overblown or unsubstantiated assertions about Hunter Biden’s business dealings there while his father was in office.
“He’s like a vacuum cleaner — he follows his father around collecting,” Mr. Trump said recently, referring to Mr. Biden’s son. “What a disgrace. It’s a crime family.”
In a misleading claim amplified by surrogates like his son Donald Trump Jr. and his lawyer Rudolph W. Giuliani, the president has said the younger Mr. Biden “walked out of China” with $1.5 billion after accompanying his father on an official trip in 2013. Numerous news articles and fact-checking sites have explained that the huge figure was actually a fund-raising goal set by an investment firm in which Hunter Biden obtained a 10 percent stake after his father left office. The firm did receive financial backing from a large state-controlled bank, but it is not clear the fund-raising target was ever met, and there is no evidence Hunter Biden received a large personal payout.
As for the former vice president, his public financial disclosures, along with the income tax returns he voluntarily released, show no income or business dealings of his own in China. However, there is ample evidence of Mr. Trump’s efforts to join the myriad American firms that have long done business there — and the tax records for him and his companies that were obtained by The Times offer new details about them.
As with Russia, where he explored hotel and tower projects in Moscow without success, Mr. Trump has long sought a licensing deal in China. His efforts go at least as far back as 2006, when he filed trademark applications in Hong Kong and the mainland. Many Chinese government approvals came after he became president. (The president’s daughter Ivanka Trump also won Chinese trademark approvals for her personal business after she joined the White House staff.)
In 2008, Mr. Trump pursued an office tower project in Guangzhou that never got off the ground. But his efforts accelerated in 2012 with the opening of a Shanghai office, and tax records show that one of Mr. Trump’s China-related companies, THC China Development L.L.C., claimed $84,000 in deductions that year for travel costs, legal fees and office expenses.
After effectively planting his flag there, Mr. Trump found a partner in the State Grid Corporation, one of the nation’s largest government-controlled enterprises. Agence France-Presse reported in 2016 that the partnership would have involved licensing and managing a development in Beijing. Mr. Trump was reportedly still pursuing the deal months into his first presidential campaign, but it was abandoned after State Grid became ensnared in a corruption investigation by Chinese authorities.
It is difficult to determine from the tax records precisely how much money Mr. Trump has spent trying to land business in China. The records show that he has invested at least $192,000 in five small companies created specifically to pursue projects there over the years. Those companies claimed at least $97,400 in business expenses since 2010, including some minor payments for taxes and accounting fees as recently as 2018.
But Mr. Trump’s plans in China have been largely driven by a different company, Trump International Hotels Management — the one with a Chinese bank account.
The company has direct ownership of THC China Development, but is also involved in management of other Trump-branded properties around the world, and it is not possible to discern from its tax records how much of its financial activity is China-related. It normally reports a few million dollars in annual income and deductible expenses.
In 2017, the company reported an unusually large spike in revenue — some $17.5 million, more than the previous five years’ combined. It was accompanied by a $15.1 million withdrawal by Mr. Trump from the company’s capital account.
On the president’s public financial disclosures for that year, he reported the large revenue figure, and described it only as “management fees and other contract payments.” One significant event for the company that is known to have occurred in 2017 was the buyout of its management contract for the SoHo hotel in New York, which Bloomberg reported to have cost around $6 million.
Mr. Garten would not comment on the specific amount cited by Bloomberg, but said that the contract buyout represented a “significant portion” of the company’s revenue and that the remaining money was not related to China.
Outside of China, Mr. Trump has had more success attracting wealthy Chinese buyers for his properties in other countries. His hotels and towers in Las Vegas and Vancouver, British Columbia — locales known for attracting Chinese real estate investors — have found numerous Chinese purchasers, and in at least one instance drew the attention of the Federal Bureau of Investigation.
During the 2016 campaign, a shell company controlled by a Chinese couple from Vancouver bought 11 units, for $3.1 million, in the Las Vegas tower Mr. Trump co-owns with the casino magnate Phil Ruffin. The owner of a Las Vegas-based financial services firm told The Times he was later visited by two F.B.I. agents asking about the company behind the purchases, which he said had used his office address in incorporation papers without his knowledge. It is not known what became of the inquiry.
Mr. Garten said the Trump Organization had “never been contacted by the F.B.I. and has no knowledge of any investigation.”
In Vancouver, numerous Chinese buyers of units in Mr. Trump’s hotel and tower helped increase licensing fees from that project to $5.8 million in 2016, the year it was completed, according to tax records. The project was built by a Canadian-based firm controlled by the family of Malaysia’s richest man, Tony Tiah Thee Kian, who operates hotels in China and elsewhere. CNN reported in 2018 that the Vancouver operation was the subject of a counterintelligence review related to Ivanka Trump’s need for a security clearance.
And not long after winning the 2016 election, Mr. Trump reported selling a penthouse in one of his Manhattan buildings for $15.8 million to a Chinese-American businesswoman named Xiao Yan Chen, who bought the unit, previously occupied by Ivanka Trump and her husband, Jared Kushner, in an off-market transaction. Ms. Chen runs an international consulting firm and reportedly has high-level connections to government and political elites in China.
Mr. Trump’s tax records show that he reported a capital gain of at least $5.6 million from the penthouse sale in 2017, his first year as president.
Jo Becker contributed reporting.
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